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1.
Food Chem X ; 23: 101767, 2024 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-39280216

RESUMO

A visual/smartphone colorimetric system was developed for the sensitive and selective detection of sulfide ion (S2-) using chemical vapor generation (CVG) as a gaseous sampling technique. S2- in samples were converted into H2S after the addition of H2SO4, which separated from the solution during CVG process, ensuring high efficiency of vapor generation (sensitivity) and eliminated interferences (selectivity). The H2S was subsequently reacted with Pb-BTC and PbS was thus formed, causing the test paper turned to black. It was utilized for the detection of S2- by visual/smartphone colorimetric system. Detectable limits of 0.05 µg/mL and 0.2 µg/mL were obtained under smartphone mode and visual mode, respectively. Furthermore, this colorimetric system was successfully used for the analysis of S2- in several beer samples and water samples, with recoveries ranging 97 %-111 %. This system represents a potential miniaturized, easy used and high-effective method for rapid and on-site detection of S2-.

2.
Angew Chem Int Ed Engl ; : e202413033, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39229697

RESUMO

Electrocatalytic nitrate reduction reaction (NO3RR) is a process that requires the participation of eight electrons and nine protons. The regulation of active hydrogen (H*) supply and a deep understanding of related processes are necessary for improving the ammonia yield rate and Faradaic efficiency (FE). Herein, we synthesized a series of atomically precise copper-halide clusters Cu2X2(BINAP)2 (X = Cl, Br, I), among which the Cu2Cl2(BINAP)2 cluster shows the optimal ammonia FE of 94.0% and an ammonia yield rate of 373 µmol h-1 cm-2. In situ experiments and theoretical calculations reveal that halogen atoms, especially Cl in Cu2Cl2(BIANP)2, can significantly affect the distance of alkali metal-ionized water on the catalyst surface, which can promote the water dissociation to enhance the localized H* enrichment for the continues hydrogenation of nitrate to ammonia. This work explains the role of H* in the hydrogenation process of NO3RR and the importance of localized H* enrichment strategy for improving the FEs.

3.
ACS Appl Mater Interfaces ; 16(40): 54627-54635, 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39347963

RESUMO

The development of intelligent reversible reconfigurable metamaterials has great significance in constructing three-dimensional metamaterials and introducing reversible tunability into metamaterials. Here, we introduce an intelligent metamaterial consisting of a two-way shape memory polymer (2W-SMP) ethylene vinyl acetate copolymer (EVA) actuator substrate and a patterned flexible-rigid film. Mechanical buckling of the 2W-SMP substrate was controlled by thermal stimulation. This makes it possible to afford an ability to initiate 3D structure formation or shape reconfiguration remotely in an on-demand fashion. In addition, the shape of the 2W-SMP substrate is temperature-dependent, allowing repeatable reversible deformation through temperature control after a single programming. Therefore, the electromagnetic properties of metamaterials can also be repeatedly and reversibly tuned between 9.15 and 10.82 GHz. Experimental demonstrations include the deformation and tunable electromagnetic properties of intelligent reversible reconfigurable metamaterial cells. The results create many opportunities for advanced programmable three-dimensional metamaterials.

4.
Biomater Adv ; 166: 214048, 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39317044

RESUMO

Designing bio-based polyurethane materials with excellent mechanical, biocompatibility, and self-healing properties simultaneously is currently a significant challenge due to the increasing demands for high-performance materials. In this study, we propose an asymmetric backbone strategy utilizing bio-based polycarbonate as the soft segment, equimolar ratios of lysine diisocyanate and isophorone diisocyanate as asymmetric hard segments, and isophorone diamine as the chain extender. The resulting polyurethane elastomers exhibit excellent mechanical properties, including high tensile stress (46.1 MPa), toughness (213.9 MJ/m3), and fracture energy (98.47 kJ/m3). The polyurethane elastomers demonstrate good self-healing and recyclable properties under simple heat treatment. Furthermore, biological experiments confirm the degradability and bio-safety of the bio-based polyurethane elastomers, which have shown potential in accelerating wound healing in mice when used as surgical sutures. These findings highlight the promising prospects of the obtained polyurethane elastomers in various applications, including biomedicine, flexible sensing, and electronic components.

5.
Environ Sci Technol ; 58(36): 16153-16163, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39178241

RESUMO

Electronic waste is an emerging source of per- and polyfluoroalkyl substance (PFAS) emissions to the environment, yet the contribution from hazardous recycling practices in the South Asian region remains unclear. This study detected 41 PFAS in soil samples from e-waste recycling sites in Pakistan and the total concentrations were 7.43-367 ng/g dry weight (dw) (median: 37.7 ng/g dw). Trifluoroacetic acid (TFA) and 6:2 fluorotelomer sulfonic acid emerged as the dominant PFAS, constituting 49% and 13% of the total PFAS concentrations, respectively. Notably, nine CF3-containing emerging PFAS were identified by the high-resolution mass spectrometry (HRMS)-based screening. Specifically, hexafluoroisopropanol and bistriflimide (NTf2) were consistently identified across all the samples, with quantified concentrations reaching up to 854 and 90 ng/g dw, respectively. This suggests their potential association with electronic manufacturing and recycling processes. Furthermore, except for NTf2, all the identified emerging PFAS were confirmed as precursors of TFA with molar yields of 8.87-40.0% by the TOP assay validation in Milli-Q water. Overall, this study reveals significant emission of PFAS from hazardous e-waste recycling practices and emphasizes the identification of emerging sources of TFA from precursor transformation, which are essential for PFAS risk assessment.


Assuntos
Resíduo Eletrônico , Reciclagem , Ácido Trifluoracético , Ácido Trifluoracético/química , Monitoramento Ambiental
6.
MMWR Morb Mortal Wkly Rep ; 73(31): 682-685, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39116024

RESUMO

Since 1994, the U.S. Vaccines for Children (VFC) program has covered the cost of vaccines for children whose families might not otherwise be able to afford vaccines. This report assessed and quantified the health benefits and economic impact of routine U.S. childhood immunizations among both VFC-eligible and non-VFC-eligible children born during 1994-2023. Diphtheria and tetanus toxoids and acellular pertussis vaccine; Haemophilus influenzae type b conjugate vaccine; oral and inactivated poliovirus vaccines; measles, mumps, and rubella vaccine; hepatitis B vaccine; varicella vaccine; pneumococcal conjugate vaccine; hepatitis A vaccine; and rotavirus vaccine were included. Averted illnesses and deaths and associated costs over the lifetimes of 30 annual cohorts of children born during 1994-2023 were estimated using established economic models. Net savings were calculated from the payer and societal perspectives. Among approximately 117 million children born during 1994-2023, routine childhood vaccinations will have prevented approximately 508 million lifetime cases of illness, 32 million hospitalizations, and 1,129,000 deaths, at a net savings of $540 billion in direct costs and $2.7 trillion in societal costs. From both payer and societal perspectives, routine childhood vaccinations among children born during 1994-2023 resulted in substantial cost savings. Childhood immunizations continue to provide substantial health and economic benefits, while promoting health equity.


Assuntos
Programas de Imunização , Humanos , Estados Unidos , Lactente , Programas de Imunização/economia , Pré-Escolar , Criança , Análise Custo-Benefício , Vacinas/administração & dosagem , Vacinas/economia , Imunização/economia , Imunização/estatística & dados numéricos
7.
Front Vet Sci ; 11: 1418760, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39100766

RESUMO

The interaction between viral proteins and host proteins plays a crucial role in the process of virus infecting cells. Tags such as HA, His, and Flag do not interfere with the function of fusion proteins and are commonly used to study protein-protein interactions. Adding these tags to viral proteins will address the challenge of the lack of antibodies for screening host proteins that interact with viral proteins during infection. Obtaining viruses with tagged fusion proteins is crucial. This study established a new reverse genetic system with T7 promoter and three plasmids, which efficiently rescued Newcastle disease virus (NDV) regardless of its ability to replicate in cells. Subsequently, using this system, NDV containing a HA-tagged structural protein and NDV carrying a unique tag on each structural protein were successfully rescued. These tagged viruses replicated normally and exhibited genetic stability. Based on tag antibodies, every NDV structural protein was readily detected and showed correct subcellular localization in infected cells. After infecting cells with NDV carrying HA-tagged M protein, several proteins interacting with the M protein during the infection process were screened using HA tag antibodies. The establishment of this system laid the foundation for comprehensive exploration of the interaction between NDV proteins and host proteins.

8.
Food Chem X ; 23: 101638, 2024 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-39113741

RESUMO

A gas pressure meter-based portable/miniaturized analytical kit was established for rapid and on-site detection of oxalate. Potassium permanganate (KMnO4) and oxalate solution were mixed together in bottle-in-bottle reaction device, a simple oxidation reaction process occurred within 6 min and carbon dioxide (CO2) was generated, inducing the pressure of the sealed bottle changed, which was measured by a portable gas pressure meter. A detectable range of 0.1-6 µmol mL-1 and a detection limit of 0.064 µmol mL-1 were achieved. The proposed analytical method was further used for the analysis of several real samples (spinach, beverages and water samples), with the recoveries of 89-111%. Considering the interferences from the complicated matrix, calcium chloride (CaCl2) was served as a precipitant, oxalate (C2O4 2-) was precipitated with Ca2+ to form precipitation (CaC2O4), CaC2O4 was then separated from the matrix by centrifuge/filter, eliminating the interferences. It is a rapid, easy-used and interference-free analytical system/device for oxalate on-site and real time analysis.

9.
Biochem Biophys Res Commun ; 727: 150317, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38959733

RESUMO

Abnormalities in osteoclastic generation or activity disrupt bone homeostasis and are highly involved in many pathologic bone-related diseases, including rheumatoid arthritis, osteopetrosis, and osteoporosis. Control of osteoclast-mediated bone resorption is crucial for treating these bone diseases. However, the mechanisms of control of osteoclastogenesis are incompletely understood. In this study, we identified that inosine 5'-monophosphate dehydrogenase type II (Impdh2) positively regulates bone resorption. By histomorphometric analysis, Impdh2 deletion in mouse myeloid lineage cells (Impdh2LysM-/- mice) showed a high bone mass due to the reduced osteoclast number. qPCR and western blotting results demonstrated that the expression of osteoclast marker genes, including Nfatc1, Ctsk, Calcr, Acp5, Dcstamp, and Atp6v0d2, was significantly decreased in the Impdh2LysM-/- mice. Furthermore, the Impdh inhibitor MPA treatment inhibited osteoclast differentiation and induced Impdh2-cytoophidia formation. The ability of osteoclast differentiation was recovered after MPA deprivation. Interestingly, genome-wide analysis revealed that the osteoclastic mitochondrial biogenesis and functions, such as oxidative phosphorylation, were impaired in the Impdh2LysM-/- mice. Moreover, the deletion of Impdh2 alleviated ovariectomy-induced bone loss. In conclusion, our findings revealed a previously unrecognized function of Impdh2, suggesting that Impdh2-mediated mechanisms represent therapeutic targets for osteolytic diseases.


Assuntos
IMP Desidrogenase , Mitocôndrias , Osteoclastos , Osteogênese , Osteoporose , Ovariectomia , Fosforilação Oxidativa , Animais , Feminino , Camundongos , Reabsorção Óssea/metabolismo , Reabsorção Óssea/genética , Reabsorção Óssea/patologia , Reabsorção Óssea/etiologia , Diferenciação Celular , IMP Desidrogenase/metabolismo , IMP Desidrogenase/genética , IMP Desidrogenase/deficiência , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Osteoclastos/metabolismo , Osteoclastos/patologia , Osteoporose/metabolismo , Osteoporose/etiologia , Osteoporose/genética , Osteoporose/patologia
10.
Cell Death Discov ; 10(1): 337, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39048556

RESUMO

Epirubicin (EPI) is effective in the treatment of malignant cancers, but its application is limited by life-threatening cardiotoxicity. Iron homeostasis disturbance has been implicated in anthracycline induced cardiotoxicity (AIC), and ferroptosis is involved in AIC which dependent upon intracellular iron. However, the role and exact mechanisms of ferroptosis in the pathogenesis of epirubicin-induced cardiotoxicity (EIC) remain elusive. In this study, we aimed to investigate mechanisms underlying ferroptosis-driven EIC. Epirubicin triggered ferroptosis both in vivo and in cultured cardiomyocytes, and pretreatment with ferroptosis inhibitor, Ferrostatin-1(Fer-1) alleviates EIC. Microarray analysis was performed to screen for potential molecules involved in EIC in neonatal primary mouse ventricular cardiomyocytes (NMVMs). We found that the transcript level of ATP6V0A2, a subunit of vacuolar ATPase (V-ATPase), was significantly downregulated when NMVMs were subjected to EPI, which was verified in vivo and in vitro as measured by real time quantitative reverse transcription PCR (qRT-PCR) and immunoblotting. Intriguingly, overexpression of ATP6V0A2 effectively decreased excessive oxidative stress and lipid-peroxidation accumulation, thereby inhibiting ferroptosis and protecting cardiomyocytes against EIC, as evidenced by functional, enzymatic, and morphological changes. Mechanistically, forced expression of ATP6V0A2 restored lysosomal acidification in EPI-treated cardiomyocytes and protected cardiomyocytes and mice hearts from ferroptosis-driven EIC. In this study, our data elucidate that ferroptosis is involved in EIC, which is ignited by ATP6V0A2-dependent lysosomal acidification dysfunction. Our study provides a new potential therapeutic target for ameliorating EIC.

11.
Sci Adv ; 10(30): eadp4533, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39058781

RESUMO

Thermogalvanic cells (TGCs) draw great attention in the field of heat to electricity conversion, but TGCs were only in the form of liquid or organic gel. Here, we report an all-inorganic hydrogel TGC via simply mixing and stirring two inorganic salt solutions. Benefiting from the hydrogen bonds resultant framework and endogenous Fe2+/3+ redox couple, the TGC can recurrently pulverize-gel with completely holding its initial thermogalvanic performances after even 60 cycles. As the temperature and pH coregulating Fe3+ concentration and reversible transformation between Fe3+ and Fe(OH)3, we boost thermopower and realize thermochromism. This work provides a different perspective for TGCs and offers an avenue for future hydrogel materials research.

12.
Biochem Pharmacol ; 226: 116391, 2024 08.
Artigo em Inglês | MEDLINE | ID: mdl-38914317

RESUMO

Inhibition of excessive osteoclastic activity is an efficient therapeutic strategy for many bone diseases induced by increased bone resorption, such as osteoporosis. BMS-582949, a clinical p38α inhibitor, is a promising drug in Phase II studies for treating rheumatoid arthritis. However, its function on bone resorption is largely unknown. In this study, we find that BMS-582949 represses RANKL-induced osteoclast differentiation in a dose-dependent manner. Moreover, BMS-582949 inhibits osteoclastic F-actin ring formation and osteoclast-specific gene expression. Mechanically, BMS-582949 treatment attenuates RANKL-mediated osteoclastogenesis through mitogen-activated protein kinases (MAPKs) and protein kinase B (AKT) signaling pathways without disturbing nuclear factor-κB (NF-κB) signaling. Interestingly, BMS-582949 impairs osteoclastic mitochondrial biogenesis and functions, such as oxidative phosphorylation (OXPHOS). Furthermore, BMS-582949 administration prevents bone loss in ovariectomized mouse mode by inhibiting both bone resorption and bone formation in vivo. Taken together, these findings indicate that BMS-582949 may be a potential and effective drug for the therapy of osteolytic diseases.


Assuntos
Camundongos Endogâmicos C57BL , Osteoclastos , Osteogênese , Ovariectomia , Proteínas Quinases p38 Ativadas por Mitógeno , Animais , Camundongos , Ovariectomia/efeitos adversos , Feminino , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Osteogênese/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Reabsorção Óssea/prevenção & controle , Reabsorção Óssea/tratamento farmacológico , Reabsorção Óssea/metabolismo , Células RAW 264.7 , Inibidores de Proteínas Quinases/farmacologia , Remodelação Óssea/efeitos dos fármacos , Ligante RANK/metabolismo , Diferenciação Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga
13.
Plants (Basel) ; 13(12)2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38931046

RESUMO

As global ecological degradation intensifies, the long-term impacts of afforestation on productivity and soil fertility in barren lands have become critical in improving global ecological security and productivity. Through meta-analysis, this study integrates data from 109 barren land afforestation sites across China, aiming to comprehensively analyze the effects on plant productivity and soil fertility while identifying the key environmental drivers of these changes. We found that afforestation consistently enhances plant productivity across 60 years. However, soil fertility and moisture initially surged significantly after afforestation but gradually declined after the first decade, indicating the limited long-term benefits. Climatic factors, namely precipitation and humidity index, are crucial in enhancing plant productivity, while geographic factors, specifically lower elevations and gentler slopes, are associated with greater increases in soil fertility. Elevation and slope are two key factors that influence soil moisture after afforestation. These findings highlight the need for ongoing soil management and ecological maintenance in afforestation projects to sustain the soil fertility benefits. Our study provides a robust scientific foundation for afforestation strategies aimed at barren land restoration and offers valuable insights for policy formulation in barren land afforestation.

14.
BMC Gastroenterol ; 24(1): 207, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38902639

RESUMO

BACKGROUND: The primary objective of this study is to comparatively assess the safety of nasogastric (NG) feeding versus nasojejunal (NJ) feeding in patients with acute pancreatitis (AP), with a special focus on the initiation of these feeding methods within the first 48 h of hospital admission. METHODS: Studies were identified through a systematic search in PubMed, EMbase, Cochrane Central Register of Controlled Trials, and Web of Science. Four studies involving 217 patients were included. This systematic review assesses the safety and efficacy of nasogastric versus nasojejunal feeding initiated within 48 h post-admission in moderate/severe acute pancreatitis, with a specific focus on the timing of initiation and patient age as influential factors. RESULTS: The results showed that the mortality rates were similar between NG and NJ feeding groups (RR 0.86, 95% CI 0.42 to 1.77, P = 0.68). Significant differences were observed in the incidence of diarrhea (RR 2.75, 95% CI 1.21 to 6.25, P = 0.02) and pain (RR 2.91, 95% CI 1.50 to 5.64, P = 0.002) in the NG group. The NG group also showed a higher probability of infection (6.67% vs. 3.33%, P = 0.027) and a higher frequency of multiple organ failures. Subgroup analysis for early intervention (within 48 h) showed a higher risk of diarrhea in the NG group (RR 2.80, P = 0.02). No significant differences were found in the need for surgical intervention, parenteral nutrition, or success rates of feeding procedures. CONCLUSION: This meta-analysis highlights the importance of considering the method and timing of nutritional support in acute pancreatitis. While NG feeding within 48 h of admission increases the risk of certain complications such as diarrhea and infection, it does not significantly impact mortality or the need for surgical intervention.


Assuntos
Nutrição Enteral , Intubação Gastrointestinal , Pancreatite , Humanos , Intubação Gastrointestinal/efeitos adversos , Intubação Gastrointestinal/métodos , Nutrição Enteral/métodos , Nutrição Enteral/efeitos adversos , Pancreatite/terapia , Pancreatite/mortalidade , Fatores de Tempo , Doença Aguda , Diarreia/etiologia , Hospitalização/estatística & dados numéricos , Jejuno
15.
Front Neuroendocrinol ; 74: 101144, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38797197

RESUMO

Ageing is inherent to all human beings, most mechanistic explanations of ageing results from the combined effects of various physiological and pathological processes. Additionally, aging pivotally contributes to several chronic diseases. Activating transcription factor 4 (ATF4), a member of the ATF/cAMP response element-binding protein family, has recently emerged as a pivotal player owing to its indispensable role in the pathophysiological processes of Alzheimer's disease and aging-related diseases. Moreover, ATF4 is integral to numerous biological processes. Therefore, this article aims to comprehensively review relevant research on the role of ATF4 in the onset and progression of aging-related diseases, elucidating its potential mechanisms and therapeutic approaches. Our objective is to furnish scientific evidence for the early identification of risk factors in aging-related diseases and pave the way for new research directions for their treatment. By elucidating the signaling pathway network of ATF4 in aging-related diseases, we aspire to gain a profound understanding of the molecular and cellular mechanisms, offering novel strategies for addressing aging and developing related therapeutics.


Assuntos
Fator 4 Ativador da Transcrição , Envelhecimento , Doença de Alzheimer , Humanos , Doença de Alzheimer/metabolismo , Doença de Alzheimer/tratamento farmacológico , Fator 4 Ativador da Transcrição/metabolismo , Envelhecimento/metabolismo , Animais , Transdução de Sinais/fisiologia
16.
Biomed Pharmacother ; 176: 116811, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38795641

RESUMO

Central nervous system (CNS) disorders exhibit exceedingly intricate pathogenic mechanisms. Pragmatic and effective solutions remain elusive, significantly compromising human life and health. Activating transcription factor 4 (ATF4) participates in the regulation of multiple pathophysiological processes, including CNS disorders. Considering the widespread involvement of ATF4 in the pathological process of CNS disorders, the targeted regulation of ATF4 by plant-derived bioactive compounds (PDBCs) may become a viable strategy for the treatment of CNS disorders. However, the regulatory relationship between PDBCs and ATF4 remains incompletely understood. Here, we aimed to comprehensively review the studies on PDBCs targeting ATF4 to ameliorate CNS disorders, thereby offering novel directions and insights for the treatment of CNS disorders. A computerized search was conducted on PubMed, Embase, Web of Science, and Google Scholar databases to identify preclinical experiments related to PDBCs targeting ATF4 for the treatment of CNS disorders. The search timeframe was from the inception of the databases to December 2023. Two assessors conducted searches using the keywords "ATF4," "Central Nervous System," "Neurological," "Alzheimer's disease," "Parkinson's Disease," "Stroke," "Spinal Cord Injury," "Glioblastoma," "Traumatic Brain Injury," and "Spinal Cord Injury." Overall, 31 studies were included, encompassing assessments of 27 PDBCs. Combining results from in vivo and in vitro studies, we observed that these PDBCs, via ATF4 modulation, prevent the deposition of amyloid-like fibers such as Aß, tau, and α-synuclein. They regulate ERS, reduce the release of inflammatory factors, restore mitochondrial membrane integrity to prevent oxidative stress, regulate synaptic plasticity, modulate autophagy, and engage anti-apoptotic mechanisms. Consequently, they exert neuroprotective effects in CNS disorders. Numerous PDBCs targeting ATF4 have shown potential in facilitating the restoration of CNS functionality, thereby presenting expansive prospects for the treatment of such disorders. However, future endeavors necessitate high-quality, large-scale, and comprehensive preclinical and clinical studies to further validate this therapeutic potential.


Assuntos
Fator 4 Ativador da Transcrição , Doenças do Sistema Nervoso Central , Fator 4 Ativador da Transcrição/metabolismo , Humanos , Doenças do Sistema Nervoso Central/tratamento farmacológico , Doenças do Sistema Nervoso Central/metabolismo , Animais , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico
17.
Schizophr Res Cogn ; 37: 100314, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38764743

RESUMO

Schizophrenia spectrum disorders (SSD) are associated with pervasive cognitive impairments, including deficits in decision-making under risk. However, there is inconclusive evidence regarding specific mechanisms underlying altered decision-making patterns. In this study, participants (33 SSD and 28 non-SSD) completed the Columbia Card Task, an explicit risk-taking task, to better understand risk preference and adjustment in dynamic decision-making. We found that while there is no group difference in overall risk-taking, risk preference, or optimal decision-making, risk adjustment to contextual factors (e.g., loss probability) is blunted in SSD. We also found associations between risk-taking/suboptimal decision-making and disorganized symptoms, excited symptoms, and role functioning, but no associations between decision-making and working memory. These results suggest that during a complex, dynamic risk-taking task, individuals with SSD exhibit less adaption to changing information about risk, which may reflect risk imperception.

18.
Comput Biol Med ; 175: 108535, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38714049

RESUMO

Gastric cancer (GC), an acknowledged malignant neoplasm, threatens life and digestive system functionality if not detected and addressed promptly in its nascent stages. The indispensability of early detection for GC to augment treatment efficacy and survival prospects forms the crux of this investigation. Our study introduces an innovative wrapper-based feature selection methodology, referred to as bCIFMVO-FKNN-FS, which integrates a crossover-information feedback multi-verse optimizer (CIFMVO) with the fuzzy k-nearest neighbors (FKNN) classifier. The primary goal of this initiative is to develop an advanced screening model designed to accelerate the identification of patients with early-stage GC. Initially, the capability of CIFMVO is validated through its application to the IEEE CEC benchmark functions, during which its optimization efficiency is measured against eleven cutting-edge algorithms across various dimensionalities-10, 30, 50, and 100. Subsequent application of the bCIFMVO-FKNN-FS model to the clinical data of 1632 individuals from Wenzhou Central Hospital-diagnosed with either early-stage GC or chronic gastritis-demonstrates the model's formidable predictive accuracy (83.395%) and sensitivity (87.538%). Concurrently, this investigation delineates age, gender, serum gastrin-17, serum pepsinogen I, and the serum pepsinogen I to serum pepsinogen II ratio as parameters significantly associated with early-stage GC. These insights not only validate the efficacy of our proposed model in the early screening of GC but also contribute substantively to the corpus of knowledge facilitating early diagnosis.


Assuntos
Detecção Precoce de Câncer , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/sangue , Detecção Precoce de Câncer/métodos , Masculino , Feminino , Algoritmos , Pessoa de Meia-Idade , Lógica Fuzzy , Idoso
19.
Proc Natl Acad Sci U S A ; 121(23): e2317790121, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38814866

RESUMO

The transformation of lung adenocarcinoma to small cell lung cancer (SCLC) is a recognized resistance mechanism and a hindrance to therapies using epidermal growth factor receptor tyrosine kinase inhibitors (TKIs). The paucity of pretranslational/posttranslational clinical samples limits the deeper understanding of resistance mechanisms and the exploration of effective therapeutic strategies. Here, we developed preclinical neuroendocrine (NE) transformation models. Next, we identified a transcriptional reprogramming mechanism that drives resistance to erlotinib in NE transformation cell lines and cell-derived xenograft mice. We observed the enhanced expression of genes involved in the EHMT2 and WNT/ß-catenin pathways. In addition, we demonstrated that EHMT2 increases methylation of the SFRP1 promoter region to reduce SFRP1 expression, followed by activation of the WNT/ß-catenin pathway and TKI-mediated NE transformation. Notably, the similar expression alterations of EHMT2 and SFRP1 were observed in transformed SCLC samples obtained from clinical patients. Importantly, suppression of EHMT2 with selective inhibitors restored the sensitivity of NE transformation cell lines to erlotinib and delayed resistance in cell-derived xenograft mice. We identify a transcriptional reprogramming process in NE transformation and provide a potential therapeutic target for overcoming resistance to erlotinib.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Transformação Celular Neoplásica , Cloridrato de Erlotinib , Neoplasias Pulmonares , Humanos , Animais , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Camundongos , Cloridrato de Erlotinib/farmacologia , Linhagem Celular Tumoral , Transformação Celular Neoplásica/genética , Regulação Neoplásica da Expressão Gênica , Resistencia a Medicamentos Antineoplásicos/genética , Via de Sinalização Wnt/genética , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/metabolismo , Carcinoma de Pequenas Células do Pulmão/patologia , Transcrição Gênica , Antígenos de Histocompatibilidade , Histona-Lisina N-Metiltransferase
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