RESUMO
Lithium-sulfur (Li-S) battery is of great potential for the next generation energy storage device due to the high specific capacity energy density. However, the sluggish kinetics of S redox and the dendrite Li growth are the main challenges to hinder its commercial application. Herein, an organic electrolyte additive, i.e., benzyl chloride (BzCl), is applied as the remedy to address the two issues. In detail, BzCl can split into Bz· radical to react with the polysulfides, forming a Bz-S-Bz intermediate, which changes the conversion path of S and improves the kinetics by accelerating the S splitting. Meanwhile, a tight and robust solid electrolyte interphase (SEI) rich in inorganic ingredients namely LiCl, LiF, and Li2O, is formed on the surface of Li metal, accelerating the ion conductivity and blocking the decomposition of the solvent and lithium polysulfides. Therefore, the Li-S battery with BzCl as the additive remains high capacity of 693.2 mAh g-1 after 220 cycles at 0.5 C with a low decay rate of 0.11%. This work provides a novel strategy to boost the electrochemical performances in both cathode and anode and gives a guide on the electrolyte design toward high-performance Li-S batteries.
RESUMO
The existing kinase inhibitors for hepatocellular carcinoma (HCC) have conferred survival benefits but are hampered by adverse effects and drug resistance, necessitating the development of novel agents targeting distinct pathways. To discover potent new anti-HCC compounds, we leveraged scaffold hopping from Sorafenib and introduced morpholine/piperidine moieties to develop ureido-substituted 4-phenylthiazole analogs with optimized physicochemical properties and binding interactions. Notably, compound 27 exhibited potent cytotoxicity against HepG2 cells (IC50 = 0.62 ± 0.34 µM), significantly exceeding Sorafenib (IC50 = 1.62 ± 0.27 µM). Mechanistic investigations revealed that compound 27 potently inhibited HCC cell migration and colony formation, and it induced G2/M arrest and early-stage apoptosis. Kinase profiling revealed IGF1R as a key target, which compound 27 potently inhibited (76.84% at 10 µM). Molecular modeling substantiated compound 27's strong binding to IGF1R via multiple hydrogen bonds. Computational predictions indicate favorable drug-like properties for compound 27. These findings provide a promising drug candidate for the treatment of HCC patients.
Assuntos
Antineoplásicos , Apoptose , Proliferação de Células , Inibidores de Proteínas Quinases , Receptor IGF Tipo 1 , Tiazóis , Humanos , Receptor IGF Tipo 1/antagonistas & inibidores , Receptor IGF Tipo 1/metabolismo , Proliferação de Células/efeitos dos fármacos , Células Hep G2 , Tiazóis/química , Tiazóis/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/síntese química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Apoptose/efeitos dos fármacos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/metabolismo , Movimento Celular/efeitos dos fármacos , Relação Estrutura-Atividade , Simulação de Acoplamento Molecular , Receptores de Somatomedina/antagonistas & inibidores , Receptores de Somatomedina/metabolismo , Estrutura Molecular , Linhagem Celular Tumoral , Sorafenibe/farmacologia , Sorafenibe/química , Modelos MolecularesRESUMO
BACKGROUND: The International Classification of Diseases, Eleventh Revision (ICD-11) improved neoplasm classification. OBJECTIVE: We aimed to study the alterations in the ICD-11 compared to the Chinese Clinical Modification of the International Classification of Diseases, Tenth Revision (ICD-10-CCM) for neoplasm classification and to provide evidence supporting the transition to the ICD-11. METHODS: We downloaded public data files from the World Health Organization and the National Health Commission of the People's Republic of China. The ICD-10-CCM neoplasm codes were manually recoded with the ICD-11 coding tool, and an ICD-10-CCM/ICD-11 mapping table was generated. The existing files and the ICD-10-CCM/ICD-11 mapping table were used to compare the coding, classification, and expression features of neoplasms between the ICD-10-CCM and ICD-11. RESULTS: The ICD-11 coding structure for neoplasms has dramatically changed. It provides advantages in coding granularity, coding capacity, and expression flexibility. In total, 27.4% (207/755) of ICD-10 codes and 38% (1359/3576) of ICD-10-CCM codes underwent grouping changes, which was a significantly different change (χ21=30.3; P<.001). Notably, 67.8% (2424/3576) of ICD-10-CCM codes could be fully represented by ICD-11 codes. Another 7% (252/3576) could be fully described by uniform resource identifiers. The ICD-11 had a significant difference in expression ability among the 4 ICD-10-CCM groups (χ23=93.7; P<.001), as well as a considerable difference between the changed and unchanged groups (χ21=74.7; P<.001). Expression ability negatively correlated with grouping changes (r=-.144; P<.001). In the ICD-10-CCM/ICD-11 mapping table, 60.5% (2164/3576) of codes were postcoordinated. The top 3 postcoordinated results were specific anatomy (1907/3576, 53.3%), histopathology (201/3576, 5.6%), and alternative severity 2 (70/3576, 2%). The expression ability of postcoordination was not fully reflected. CONCLUSIONS: The ICD-11 includes many improvements in neoplasm classification, especially the new coding system, improved expression ability, and good semantic interoperability. The transition to the ICD-11 will inevitably bring challenges for clinicians, coders, policy makers and IT technicians, and many preparations will be necessary.
RESUMO
Ultrafine iridium particles anchored on nitrogen-doped CNTs were obtained from Ir(ppy)3 and CNTs using a simple annealing method and acted as highly efficient bifunctional oxygen catalysts for Zn-air batteries. A synergistic effect, efficient *OH adsorption and rapid *OOH deprotonation were demonstrated from in situ FTIR spectroscopy, EIS and activation energy measurements.
RESUMO
Phospholipid complexes of alkyl gallates (A-GAs) including ethyl gallate (EG), propyl gallate (PG), and butyl gallate (BG) were successfully prepared by the thin film dispersion method. HPLC-UV analysis in an everted rat gut sac model indicated that A-GAs can be liberated from phospholipid complexes, which were further hydrolyzed by intestinal lipase to generate free gallic acid (GA). Both A-GAs and GA are able to cross the membrane, and the hydrolysis rate of A-GAs and the transport rate of GA are positively correlated with the alkyl chain length. Especially, compared with the corresponding physical mixtures, the phospholipid complexes exhibit slower sustained-release of A-GAs and GA. Therefore, the formation of phospholipid complexes is an effective approach to prolong the residence time in vivo and additionally enhance the bioactivities of A-GAs and GA. More importantly, through regulating the carbon skeleton lengths, controlled-release of alkyl gallates and gallic acid from phospholipid complexes will be achieved.
Assuntos
Ácido Gálico , Fosfolipídeos , Ratos , Animais , Preparações de Ação Retardada , Hidrólise , Galato de PropilaRESUMO
ß-thalassemia, a globally prevalent genetic disorder, urgently requires innovative treatment options. Fetal hemoglobin (HbF) induction stands as a key therapeutic approach. This investigation focused on Ginsenoside Rg1 from the Panax genus for HbF induction. Employing K562 cells and human erythroid precursor cells (ErPCs) derived from neonatal cord blood, the study tested Rg1 at different concentrations. We measured its effects on γ-globin mRNA levels and HbF expression, alongside assessments of cell proliferation and differentiation. In K562 cells, Rg1 at 400 µM significantly increased γ-globin mRNA expression by 4.24 ± 1.08-fold compared to the control. In ErPCs, the 800 µM concentration was most effective, leading to an over 80% increase in F-cells and a marked upregulation in HbF expression. Notably, Rg1 did not adversely affect cell proliferation or differentiation, with the 200 µM concentration showing an increase in γ-globin mRNA by 2.33 ± 0.58-fold, and the 800 µM concentration enhancing HbF expression by 2.59 ± 0.03-fold in K562 cells. Our results underscore Rg1's potential as an effective and safer alternative for ß-thalassemia treatment. By significantly enhancing HbF levels without cytotoxicity, Rg1 offers a notable advantage over traditional treatments like Hydroxyurea. While promising, these in vitro findings warrant further in vivo exploration to confirm Rg1's therapeutic efficacy and to unravel its underlying mechanistic pathways.
Assuntos
Ginsenosídeos , Talassemia beta , Recém-Nascido , Humanos , Talassemia beta/genética , Hemoglobina Fetal , gama-Globinas/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
Ethanol evaporation method was applied to synthesize phospholipid complexes from phosphatidylcholine (PC) and short-chain alkyl gallates (A-GAs, a typical representative of lipophenols) including butyl-, propyl- and ethyl gallates. 1H NMR, UV and FTIR showed that A-GAs were interacted with PC through weak physical interaction. Through the analysis of concentrations of A-GAs and gallic acid (GA) by an everted rat gut sac model coupled with HPLC-UV detection, phospholipid complexes were found to gradually release A-GAs. These liberated A-GAs were further hydrolyzed by intestinal lipases to release GA. Both of GA and A-GAs could cross intestinal membrane. Especially, the transmembrane A-GAs could also be hydrolyzed to produce GA. Undoubtedly, the dual release of phenol compounds from phospholipid complexes of short-chain lipophenols will be effective to extend the in vivo residence period of phenol compounds. More importantly, such behavior is easily adjusted by changing the acyl chain lengths of lipophenols in phospholipid complexes.
Assuntos
Fenóis , Fosfolipídeos , Animais , Ratos , Fenóis/química , Fosfolipídeos/química , Masculino , Ácido Gálico/química , Preparações de Ação Retardada/química , Ratos Sprague-DawleyRESUMO
The ß-cyclodextrin and short-chain alkyl gallates (A-GAs), which are representative of phenolipids, such as butyl, propyl, ethyl, and methyl gallates, were chosen to form inclusion complexes by the use of the freeze-drying process. In the everted rat gut sac model, HPLC-UV analysis demonstrated that the released A-GAs from inclusion complexes were degraded to yield free gallic acid (GA) (sustained-release function 1). The small intestine membrane may be crossed by both the GA and the A-GAs. A-GAs may also undergo hydrolysis to provide GA (sustained-release function 2) following transmembrane transfer. Clearly, a helpful technique for the dual sustained-release of phenolic compounds is to produce ß-cyclodextrin inclusion complexes with short-chain phenolipids. This will increase the bioactivities of phenolic compounds and prolong their in vivo residence length. Moreover, changing the carbon-chain length of these ß-cyclodextrin inclusion complexes would readily modify the dual sustained-release behavior of the phenolic compounds. Thus, our work effectively established a theoretical foundation for the use of ß-cyclodextrin inclusion complexes containing short-chain phenolipids as new source of functional food components to provide the body with phenolic compounds more efficiently.
Assuntos
Preparações de Ação Retardada , Ácido Gálico , Fenóis , beta-Ciclodextrinas , beta-Ciclodextrinas/química , Animais , Ratos , Ácido Gálico/química , Masculino , Fenóis/química , Ratos Sprague-Dawley , LiofilizaçãoRESUMO
HPLC-UV analysis was used to evaluate the enzymatic degradation characteristics of tyrosol acyl esters (TYr-Es) and alkyl gallates (A-GAs). Among various hydrolytic enzymes, TYr-Es can be hydrolyzed by pancrelipase, while A-GAs cannot be hydrolyzed by pancrelipase. Interestingly, carboxylesterase-1b (CES-1b), carboxylesterase-1c (CES-1c) and carboxylesterase-2 (CES-2) are able to hydrolyze TYr-Es and A-GAs, and thus to liberate tyrosol (TYr) and gallic acid (GA). By contrast, the degrees of hydrolysis (DHs) of TYr-Es and A-GAs by CES-1b and CES-1c were significantly higher than those by CES-2. Meanwhile, the DHs of TYr-Es were much higher than those of A-GAs. Especially, the DHs firstly increased and then decreased with the increasing alkyl chain length. Besides, DHs positively correlated with the unsaturation degree at the same chain length. Through regulating carbon length, unsaturation degree and the ester bond structure, controlled-release of phenolic compounds and fatty acids (or fatty alcohols) from phenolic esters will be easily achieved.
Assuntos
Ésteres , Ácido Gálico , Álcool Feniletílico/análogos & derivados , Hidrólise , Ácido Gálico/química , Ésteres/química , Pancrelipase , Cromatografia Líquida de Alta PressãoRESUMO
Based on the observed biological activity of 1,2,4-triazin-5-one derivatives and their cyclic analogues, a novel series of 7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives that contain ester moiety compounds 3a-3g, carboxylic acid moiety compounds 4a-4g and piperazine amide moiety compounds 5a-5k at position-3 of the thiazolotriazinone scaffold were synthesized. The intermolecular cyclization occurred regioselectively at N2-position of 1,2,4-triazine ring was characterized by X-ray single-crystal diffraction analysis. The in vitro biological activities of the target compounds were assayed against some bacterial strains. Compared with ciprofloxacin, compounds 3g and 4g exhibited more excellent antibacterial activity, especially the activity against Staphylococcus aureus and Escherichia coli, showing that the fluorine at the para position of the benzyl group would be the best choice. In addition, compounds 4e-4g with carboxylic acid moiety can enhance the antibacterial activity. Compounds 5g-5k containing bulky 1-(substituted phenyl)piperazine moiety were found with slightly less biological activity. Similar to ciprofloxacin, the docking result of target compounds with DNA topoisomerase II indicates the carboxyl group of the target compounds with carboxylic acid moiety has a crucial salt bridge interaction with Mg2+ in the protein.
RESUMO
OBJECTIVES: As a novel type of theta burst stimulation (TBS), continuous TBS (cTBS) has been shown to have mixed therapeutic effects for major depressive disorder (MDD) or bipolar depression (BD). Thus, we performed a meta-analysis of randomized controlled trials (RCTs) of cTBS for treating major depressive episodes in patients with MDD or BD. METHODS: A systematic search of four major bibliographic databases (PubMed, EMBASE, Cochrane Library, and PsycINFO) was conducted from inception dates to February 3, 2023 to identify eligible studies. The data were analyzed using a random-effects model. RESULTS: Three RCTs (n = 78, active cTBS = 37 and sham cTBS = 41) were included the meta-analysis. No significant differences were found in terms of change in Hamilton Depression Rating Scale (HAMD) scores (3 RCTs, n = 78, SMD = -0.09, 95 % CI: -0.53 to 0.36; I2 = 0 %; P = 0.71) and study-defined response (2 RCTs, n = 58, 26.7 % versus 21.4 %, RR = 1.20, 95 % CI: 0.48 to 2.96; I2 = 0 %; P = 0.70) between active and sham cTBS groups. Similarly, no group differences were found in the rates of adverse events and discontinuation due to any reason (P > 0.05). LIMITATIONS: Meta-analysis had small sample sizes and low number of included studies. CONCLUSIONS: Although cTBS appeared to be a safe and well-tolerated option for treating major depressive episodes in MDD or BD patients, no advantage in treatment effects was found in this meta-analysis. Future large-scale studies are warranted to assess the efficacy of cTBS for MDD or BD patients with a major depressive episode.
Assuntos
Transtorno Bipolar , Transtorno Depressivo Maior , Humanos , Transtorno Bipolar/tratamento farmacológico , Bases de Dados Bibliográficas , Transtorno Depressivo Maior/tratamento farmacológico , Projetos de Pesquisa , Estimulação Magnética Transcraniana , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
The efficacy and safety of deep transcranial magnetic stimulation (dTMS) in treating treatment-resistant depression (TRD) are unknown. Up to June 21, 2023, we conducted a systematic search for RCTs, and then extracted and synthesized data using random effects models. Five RCTs involving 507 patients with TRD (243 in the active dTMS group and 264 in the control group) were included in the present study. The active dTMS group showed significantly higher study-defined response rate (45.3% versus 24.2%, n = 507, risk ratio [RR] = 1.87, 95% confidence interval [CI]: 1.21-2.91, I2 = 53%; P = 0.005) and study-defined remission rate (38.3% versus 14.4%, n = 507, RR = 2.37, 95%CI: 1.30-4.32, I2 = 58%; P = 0.005) and superiority in improving depressive symptoms (n = 507, standardized mean difference = -0.65, 95%CI: -1.11--0.18, I2 = 82%; P = 0.006) than the control group. In terms of cognitive functions, no significant differences were observed between the two groups. The two groups also showed similar rates of other adverse events and all-cause discontinuations (P > 0.05). dTMS is an effective and safe treatment strategy for the management of patients with TRD.
Assuntos
Transtorno Depressivo Resistente a Tratamento , Estimulação Magnética Transcraniana , Humanos , Transtorno Depressivo Resistente a Tratamento/terapia , Avaliação de Resultados em Cuidados de Saúde , Ensaios Clínicos Controlados Aleatórios como Assunto , Estimulação Magnética Transcraniana/métodos , Resultado do TratamentoRESUMO
The freeze-drying approach was used to create inclusion complexes utilizing alkyl gallates and ß-cyclodextrin, namely dodecyl gallate, octyl gallate, butyl gallate, and ethyl gallate, which are exemplary examples of phenolic esters. The everted-rat-gut-sac model demonstrated that the inclusion complexes released alkyl gallates, which were subsequently hydrolyzed to generate free gallic acid, as evidenced by HPLC-UV analysis. Both gallic acid and short-chain alkyl gallates were capable of permeating the small intestinal membrane. The transport rate of gallic acid (or alkyl gallates) exhibited an initial rise followed by a drop when the carbon-chain lengths varied. The inclusion complex groups exhibited a superior sustained-release effect compared to the comparable alkyl gallates groups, thus possibly leading to higher bioavailability and stronger bioactivity. Moreover, altering the length of the carbon chain will allow for the effortless achievement of regulated release of phenolic compounds and short-chain phenolic esters from such ß-cyclodextrin inclusion complexes.
RESUMO
To investigate the significance of atherosclerotic plaque location in hybrid surgery comprising both endovascular recanalization approaches and carotid endarterectomy for symptomatic atherosclerotic non-acute long-segment occlusion of the internal carotid artery (ICA), 162 patients were enrolled, including 120 (74.1%) patients in the proximal plaque group and 42 (25.9%) in the distal plaque group. Surgical recanalization was performed in all patients, with successful recanalization in 119 (99.2%) patients in the proximal and 39 (92.9%) in the distal plaque group. The total successful recanalization rate was 97.5% (158/162) with a failure rate of 2.5% (4/162). Periprocedural complications occurred in 5 (4.2% or 5/120) patients in the proximal plaque group, including neck infection in two (1.7%), recurrent nerve injury in 1 (0.8%), and laryngeal edema in 2 (1.7%), and 2 (4.8%) in the distal plaque group, including femoral puncture infection in 2 (4.8%). No severe complications occurred in either group. Univariate analysis showed plaque location was a significant (P = 0.018) risk factor for successful recanalization, and multivariate analysis indicated that the plaque location remained a significant independent risk factor for recanalization success (P = 0.017). In follow-up 6-48 months after the recanalization surgery, reocclusion occurred in two (2.8%) patients in the proximal plaque group and 4 (13.3%) in the distal plaque group. In conclusion, although hybrid surgery achieves similar outcomes in patients with ICA occlusion caused by either proximal or distal atherosclerotic plaques, plaque location may be a significant risk factor for successful recanalization of symptomatic non-acute long-segment ICA occlusion.
Assuntos
Artéria Carótida Interna , Estenose das Carótidas , Endarterectomia das Carótidas , Placa Aterosclerótica , Humanos , Masculino , Feminino , Idoso , Placa Aterosclerótica/cirurgia , Placa Aterosclerótica/patologia , Placa Aterosclerótica/complicações , Artéria Carótida Interna/cirurgia , Artéria Carótida Interna/patologia , Pessoa de Meia-Idade , Estenose das Carótidas/cirurgia , Estenose das Carótidas/patologia , Estenose das Carótidas/complicações , Endarterectomia das Carótidas/métodos , Resultado do Tratamento , Procedimentos Endovasculares/métodos , Idoso de 80 Anos ou mais , Fatores de RiscoRESUMO
Stress-adaptive mechanisms enabling cancer cells to survive under glucose deprivation remain elusive. N6-methyladenosine (m6A) modification plays important roles in determining cancer cell fate and cellular stress response to nutrient deficiency. However, whether m6A modification functions in the regulation of cancer cell survival under glucose deprivation is unknown. Here, we found that glucose deprivation reduced m6A modification levels. Increasing m6A modification resulted in increased hepatoma cell necrosis under glucose deprivation, whereas decreasing m6A modification had an opposite effect. Integrated m6A-seq and RNA-seq revealed potential targets of m6A modification under glucose deprivation, including the transcription factor FOSL1; further, glucose deprivation upregulated FOSL1 by inhibiting FOSL1 mRNA decay in an m6A-YTHDF2-dependent manner through reducing m6A modification in its exon1 and 5'-UTR regions. Functionally, FOSL1 protected hepatoma cells against glucose deprivation-induced necrosis in vitro and in vivo. Mechanistically, FOSL1 transcriptionally repressed ATF3 by binding to its promoter. Meanwhile, ATF3 and MAFF interacted via their leucine zipper domains to form a heterodimer, which competed with NRF2 for binding to antioxidant response elements in the promoters of NRF2 target genes, thereby inhibiting their transcription. Consequently, FOSL1 reduced the formation of the ATF3-MAFF heterodimer, thereby enhancing NRF2 transcriptional activity and the antioxidant capacity of glucose-deprived-hepatoma cells. Thus, FOSL1 alleviated the necrosis-inducing effect of glucose deprivation-induced reactive oxygen species accumulation. Collectively, our study uncovers the protective role of m6A-FOSL1-ATF3 axis in hepatoma cell necrosis under glucose deprivation, and may provide new targets for cancer therapy.
Assuntos
Carcinoma Hepatocelular , Glucose , Neoplasias Hepáticas , Necrose , Proteínas Proto-Oncogênicas c-fos , RNA Mensageiro , Proteínas Proto-Oncogênicas c-fos/metabolismo , Proteínas Proto-Oncogênicas c-fos/genética , Glucose/metabolismo , Glucose/deficiência , Humanos , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/genética , Animais , Camundongos , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , Linhagem Celular Tumoral , Fator 3 Ativador da Transcrição/metabolismo , Fator 3 Ativador da Transcrição/genética , Adenosina/análogos & derivados , Adenosina/metabolismo , Camundongos NusRESUMO
To investigate the effect and safety of percutaneous endovascular angioplasty (PEA) with optional stenting for the treatment of severe stenosis or occlusion of subclavian artery, patients with severe stenosis ≥ 70% or occlusion of subclavian artery treated with PEA were retrospectively enrolled. The clinical data were analyzed. A total of 222 patients were retrospectively enrolled, including 151 males (68.0%) and 71 females (32.0%) aged 48-86 (mean 63.9 ± 9.0) years. Forty-seven (21.2%) patients had comorbidities. Subclavian artery stenosis ≥ 70% was present in 201 (90.5%) patients and complete subclavian occlusion in 21 (9.5%) cases. Angioplasty was successfully performed in all (100%) patients. Balloon-expandable stents were used in 190 (85.6%) cases, and self-expandable stents in 20 (9.0%) cases. Only 12 (5.4%) cases were treated with balloon dilation only. Among 210 patients treated with stent angioplasty, 71 (33.8% or 71/210) cases underwent balloon pre-dilation, 139 (66.2% or 139/210) had direct deployment of balloon-expandable stents, and 2 (1.0% or 2/210) experienced balloon post-dilation. Distal embolization protection devices were used in 5 (2.3% or 5/222) cases. Periprocedural complications occurred in 3 (1.4%) patients, including aortic dissection in 2 (0.9%) cases and right middle cerebral artery embolism in 1 (0.5%). No hemorrhage occurred. Among 182 (82.0%) patients with 6-month follow-up, restenosis > 70% occurred in 1 (0.5%) patient, and among 68 (30.6%) patients with 12-month follow-up, restenosis > 70% took place in 11 (16.2%) patients. Percutaneous endovascular angioplasty can be safely and efficiently performed for the treatment of severe stenosis ≥ 70% or occlusion of subclavian artery.
Assuntos
Stents , Artéria Subclávia , Humanos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Artéria Subclávia/cirurgia , Estudos Retrospectivos , Stents/efeitos adversos , Resultado do Tratamento , Síndrome do Roubo Subclávio/terapia , Síndrome do Roubo Subclávio/cirurgia , Procedimentos Endovasculares/métodos , Procedimentos Endovasculares/efeitos adversos , Angioplastia/métodos , Angioplastia/efeitos adversos , Constrição Patológica/terapia , Angioplastia com Balão/métodos , Angioplastia com Balão/efeitos adversos , Arteriopatias Oclusivas/terapia , Arteriopatias Oclusivas/cirurgiaRESUMO
Purpose: Acute ischemic stroke (AIS) has seriously threatened people's health worldwide and there is an urge need for early diagnosis and effective treatment of AIS. This research intended to clarify the regulatory role of circ_0008146/miR-342-5p/ACSL4 axis in AIS. Methods: High-throughput small RNA sequencing analysis was adapted to identify differentially expressed miRNAs between the AIS and control group. The circ_0008146, miR-342-5p, and ACSL4 levels were detected by qRT-PCR. Middle cerebral artery occlusion/reperfusion (MCAO/R) models were constructed in C57BL/6J mice. Assay kits were used to determine Fe2+ levels and a battery of oxidative stress and lipid peroxidation indicators, including ROS, MDA, LPO, SOD and GSH/GSSG ratio. The protein levels of ACSL4 were measured by Western blot. The behavioral function was assessed using neurobehavioral tests. TTC staining was employed to visualize infarction size. Nissl staining was adapted to detect histopathological changes. Receiver operating characteristic curve and correlation analysis were applied to investigate the clinical value and association of miR-342-5p and ACSL4. Results: A total of 44 AIS patients and 49 healthy controls were enrolled in our study. The small RNA sequencing unveiled a significant decrease in miR-342-5p levels in AIS patients. MiR-342-5p inhibited oxidative stress and RSL3-induced ferroptosis after cerebral ischemic/reperfusion injury in vivo by targeting ferroptosis-related gene ACSL4. Circ_0008146 acted as a sponge of miR-342-5p, and overexpression of circ_0008146 increased neurological deficits and brain injury in mice. Circ_0008146 contributed to ferroptosis in cerebral infarction via sponging miR-342-5p to regulate ACSL4. Plasma miR-342-5p and ACSL4 demonstrated significant correlation and good diagnostic value for AIS patients. Conclusion: This study provides the first in vivo evidence to show that circ_0008146 exacerbates neuronal ferroptosis after AIS via the miR-342-5p/ACSL4 axis. Furthermore, miR-342-5p/ACSL4 axis holds promise as a viable therapeutic target and practical biomarkers for AIS patients.
RESUMO
Illegal food production in China has proliferated in recent years, triggering serious public concerns on food safety. In this work, we model a regulatory event in a food supply chain comprising a local government, a dealer, and a producer involved in illegal food production, and get equilibrium regulatory decisions of the government and the dealer, and equilibrium production decisions of the producer. The results show that: 1) in a situation where the producer is likely to produce illegally, the government does not regulate, and implements insufficient or sufficient regulation according to the utility-cost ratio of regulating. 2) The regulatory decisions of the dealer depend not only on the regulatory decisions of the government but also on the utility-cost ratio of regulating. 3) Only when the joint regulatory intensity of the government and the dealer is not less than a certain threshold value, the producer will not produce illegally, and the threshold value is the optimal regulatory intensity jointly implemented by the government and the dealer. Otherwise it is ineffective, inadequate, or excessive regulation. Therefore, we suggest that the government and the dealer jointly make regulatory decisions to achieve optimal regulation at the lowest regulatory cost and evade illegal food production by the producer.
RESUMO
Objective: This systematic review of randomized controlled studies (RCTs) and observational studies evaluated the efficacy and safety of stanford neuromodulation therapy (SNT) for patients with treatment-resistant depression (TRD). Methods: A systematic search (up to 25 September, 2023) of RCTs and single-arm prospective studies was conducted. Results: One RCT (n = 29) and three single-arm prospective studies (n = 34) met the study entry criteria. In the RCT, compared to sham, active SNT was significantly associated with higher rates of antidepressant response (71.4% versus 13.3%) and remission (57.1% versus 0%). Two out of the three single-arm prospective studies reported the percentage of antidepressant response after completing SNT, ranging from 83.3% (5/6) to 90.5% (19/21). In the three single-arm prospective studies, the antidepressant remission rates ranged from 66.7% (4/6) to 90.5% (19/21). No severe adverse events occurred in all the four studies. Conclusion: This systematic review found SNT significantly improved depressive symptoms in patients with TRD within 5 days, without severe adverse events.