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1.
Phys Chem Chem Phys ; 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39279627

RESUMO

Ferroelectric ß-phase crystals of a polyvinylidene fluoride (PVDF) polymer grown or deposited on a graphene channel of a field effect transistor would induce various degrees of electrostatic doping (i.e., various amounts of charge carriers) into graphene and in turn ON/OFF switching of the device, only if the electric field applied at the gate can reorient its polarization (i.e., the well-aligned F-to-H dipole moments perpendicular to the all-trans polymer backbone) around the polymer backbone. To assess the feasibility of achieving a ß-PVDF/graphene ferroelectric field effect transistor or memory device, we mimic (1) the electric-field-controlled PVDF polarization reversal (with density functional theory calculations and molecular dynamics simulations) and (2) the conductance switching of ß-PVDF/graphene by PVDF reorientations (F-, H- and FH-down) representing a cycle of gate-voltage sweep (with density functional theory combined with non-equilibrium Green's function formalism). The low energy barrier of the collective synchronous PVDF chain rotation around the backbone (0.22 eV per monomer) and the high electric field required to initiate the chain rotation (16 V nm-1) are compatible with the domain nucleation-growth theory and would support the polarization-induced resistance switching mechanism if the PVDF film is ultrathin and partially amorphous.

2.
J Chem Theory Comput ; 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39240127

RESUMO

Exploring potential energy surfaces (PES) is essential for unraveling the underlying mechanisms of chemical reactions and material properties. While the activation-relaxation technique (ARTn) is a state-of-the-art method for identifying saddle points on PES, it often faces challenges in complex energy landscapes, especially on surfaces. In this study, we introduce iso-ARTn, an enhanced ARTn method that incorporates constraints on an orthogonal hyperplane and employs an adaptive active volume. By leveraging a neural network potential (NNP) to conduct an exhaustive saddle point search on the Pt(111) surface with 0.3 monolayers of surface oxygen coverage, iso-ARTn achieves a success rate that is 8.2% higher than the original ARTn, with 40% fewer force calls. Moreover, this method effectively finds various saddle points without compromising the success rate. Combined with kinetic Monte Carlo simulations for event table construction, iso-ARTn with NNP demonstrates the capability to reveal structures consistent with experimental observations. This work signifies a substantial advancement in the investigation of PES, enhancing both the efficiency and breadth of saddle point searches.

3.
Allergy Asthma Immunol Res ; 16(4): 387-398, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39155738

RESUMO

PURPOSE: Limited knowledge exists regarding the psychosocial characteristics of young Asian children affected by food allergies (FAs) and their caregivers. This study aims to assess the usefulness of the Food Allergy Severity Score (FASS) system in evaluating the risk of emotional impacts on young children and caregivers who are dealing with severe FA. METHODS: Children between 2 and 10 years of age who were diagnosed with FA and following an elimination diet were enrolled in the study. The FASS, Korean Parenting Stress Index, and Korean Behavior Assessment System for Children-2 were used for evaluating the above mentioned risk. RESULTS: Among the 75 participants, 64.0% had a history of anaphylaxis, and 56.0% reported multiple FAs. A total of 160 cases of FASS was documented across 21 types of food and classified as mild (n = 5, 1.07), moderate (n = 100, 2.01-4.01), or severe (n = 55, 4.24-6.84). The concordance of calculated- and stakeholder interpreted-FASS was moderate (kappa 0.587). Children with severe FASS (sFASS) showed increased risk for functional communication (relative risk [RR], 1.57; 95% confidence interval [CI], 0.99-2.48) and increased parental reinforcement (RR, 1.40; 95% CI, 0.91-2.14). Their caregivers exhibited reduced levels of demandingness (RR, 0.59; 95% CI, 0.37-0.94) and role restriction (RR, 0.62; 95% CI, 0.39-0.98). Receiver operating characteristic curves suggested that functional communication (numeric FASS cutoff, 3.47; area under the curve [AUC], 0.695), withdrawal (cutoff, 3.40; AUC, 0.657), developmental social disorders (cutoff, 3.96; AUC, 0.648), and reinforces parent (cutoff, 3.15; AUC, 0.646) were possibly be affected. CONCLUSIONS: The FASS provides an objective tool to assess pediatric FA severity. Early psychosocial intervention for young children with severe FASS and their caregivers may improve prognosis by identifying possible adaptive skill deficiencies and excessive parenting stresses.

4.
J Korean Med Sci ; 39(31): e226, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39137811

RESUMO

BACKGROUND: Despite a plethora of research on the topic, there is still no solid evidence that pharmacological treatment actually reduces the risk of suicide in patients with mental illness. In this study, we aimed to assess the effect of psychotropic medications on suicidal ideation in patients with major depressive disorder (MDD) and bipolar disorder (BPD) in two age groups: less than 25 years and 25 years and older. METHODS: We analyzed 312 patients with mood disorders with current suicidal thoughts or recent suicide attempts. We followed the participants from baseline for 6 months and assessed changes in suicidal ideation with Columbia-Suicide Severity Rating Scale (C-SSRS). The effect of psychotropic drug administration on suicidal ideation over time was analyzed using a linear mixed model. RESULTS: In patients aged 25 years and older with mood disorders, suicidal ideation was more severe when using psychotropic drugs than when not using them. However, suicidal ideation decreased rapidly over time. The time-dependent reduction in suicidal ideation was accelerated when using antidepressants and sedatives/hypnotics in adult MDD, and when using mood stabilizers in adult BPD. However, this effect was not observed in participants aged less than 25 years. CONCLUSION: Adequate psychotropic medication may reduce suicidal ideation in patients with mood disorders aged 25 years and older. Additional research on psychotropic drugs is needed to effectively reduce the risk of suicide among children and adolescents with mood disorders.


Assuntos
Transtorno Bipolar , Transtorno Depressivo Maior , Psicotrópicos , Ideação Suicida , Humanos , Adulto , Masculino , Feminino , Estudos Prospectivos , Psicotrópicos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/psicologia , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/psicologia , Adulto Jovem , Antidepressivos/uso terapêutico , Transtornos do Humor/tratamento farmacológico , Transtornos do Humor/psicologia , Pessoa de Meia-Idade , Tentativa de Suicídio/psicologia , Adolescente , Fatores de Tempo
5.
J Psychiatr Res ; 176: 442-451, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38981238

RESUMO

Despite previous efforts to build statistical models for predicting the risk of suicidal behavior using machine-learning analysis, a high-accuracy model can lead to overfitting. Furthermore, internal validation cannot completely address this problem. In this study, we created models for predicting the occurrence of suicide attempts among Koreans at high risk of suicide, and we verified these models in an independent cohort. We performed logistic and penalized regression for suicide attempts within 6 months among suicidal ideators and attempters in The Korean Cohort for the Model Predicting a Suicide and Suicide-related Behavior (K-COMPASS). We then validated the models in a test cohort. Our findings indicated that several factors significantly predicted suicide attempts in the models, including young age, suicidal ideation, previous suicidal attempts, anxiety, alcohol abuse, stress, and impulsivity. The area under the curve and positive predictive values were 0.941 and 0.484 after variable selection and 0.751 and 0.084 in the test cohort. The corresponding values for the penalized regression model were 0.943 and 0.524 in the original training cohort and 0.794 and 0.115 in the test cohort. The prediction model constructed through a prospective cohort study of the suicide high-risk group showed satisfactory accuracy even in the test cohort. The accuracy with penalized regression was greater than that with the "classical" logistic model.


Assuntos
Aprendizado de Máquina , Ideação Suicida , Tentativa de Suicídio , Humanos , Tentativa de Suicídio/estatística & dados numéricos , Masculino , Feminino , República da Coreia/epidemiologia , Adulto , Adulto Jovem , Estudos Prospectivos , Modelos Logísticos , Pessoa de Meia-Idade , Adolescente , Fatores de Risco
6.
ACS Appl Mater Interfaces ; 16(28): 37157-37166, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-38950350

RESUMO

Area-selective atomic layer deposition (AS-ALD), which provides a bottom-up nanofabrication method with atomic-scale precision, has attracted a great deal of attention as a means to alleviate the problems associated with conventional top-down patterning. In this study, we report a methodology for achieving selective deposition of high-k dielectrics by surface modification through vapor-phase functionalization of octadecylphosphonic acid (ODPA) inhibitor molecules accompanied by post-surface treatment. A comparative evaluation of deposition selectivity of ZrO2 thin films deposited with the O2 and O3 reactants was performed on SiO2, TiN, and W substrates, and we confirmed that high enough deposition selectivity over 10 nm can be achieved even after 200 cycles of ALD with the O2 reactant. Subsequently, the electrical properties of ZrO2 films deposited with O2 and O3 reactants were investigated with and without post-deposition treatment. We successfully demonstrated that high-quality ZrO2 thin films with high dielectric constants and stable antiferroelectric properties can be produced by subjecting the films to ozone, which can eliminate carbon impurities within the films. We believe that this work provides a new strategy to achieve highly selective deposition for AS-ALD of dielectric on dielectric (DoD) applications toward upcoming bottom-up nanofabrication.

7.
ACS Appl Mater Interfaces ; 16(30): 39427-39436, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39028895

RESUMO

Li metal, with a high theoretical capacity, is considered the most promising anode for next-generation high-energy-density batteries. However, the commercialization of the Li metal anode is limited owing to its high reactivity, significant volume expansion, continuous solid electrolyte interphase (SEI) layer degradation caused by undesirable Li deposition, and uncontrollable dendrite growth. This study demonstrates the in situ construction of a Li2C2O4-enriched SEI layer from NiC2O4 nanowires on three-dimensional Ni foam. The lithiophilic Li2C2O4-enriched SEI layer provides a uniform distribution of the electrical field and sufficient nucleation and deposition sites for Li without dendrite formation. Consequently, the stable Li2C2O4-enriched SEI layer successfully inhibits the formation of lithium dendrites, resulting in reversible Li stripping/plating behavior, maintained over an extended period of 5000 h with a deposition capacity of 1 mAh cm-2 at 1 mA cm-2. Additionally, a high cycling stability is observed in the full cell test with ∼70% capacity retention after 1300 cycles at 3 C. This approach offers a large-scale and facile synthesis process via the in situ precipitation growth of NiC2O4 followed by lithiation to form Li2C2O4. Furthermore, the significant stability of the Li2C2O4-enriched SEI layer aids the design of in situ-constructed SEI layers for highly stable Li metal batteries.

8.
BMC Psychiatry ; 24(1): 485, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956575

RESUMO

BACKGROUND: Suicide rates in older adults are much higher than those in younger age groups. Given the rapid increase in the proportion of older adults in Korea and the high suicide rate of this age group, it is worth investigating the mechanism of suicidal ideation for older adults. Generally, adverse childhood experiences are positively associated with suicidal ideation; however, it is not fully understood what mediating relationships are linked to the association between these experiences and current suicidal ideation. METHODS: The data from 685 older Korean adults were analyzed utilizing logistic regression, path analyses, and structural equation modeling. Based on our theoretical background and the empirical findings of previous research, we examined three separate models with mental health, physical health, and social relationship mediators. After that, we tested a combined model including all mediators. We also tested another combined model with mediation via mental health moderated by physical health and social relationships. RESULTS: The univariate logistic regression results indicated that childhood adversity was positively associated with suicidal ideation in older adults. However, multivariate logistic regression results demonstrated that the direct effect of childhood adversity became nonsignificant after accounting all variables. Three path models presented significant mediation by depression and social support in the association between childhood adversity and suicidal ideation. However, combined structural equation models demonstrated that only mediation by a latent variable of mental health problems was statistically significant. Social relationships moderated the path from mental health problems to suicidal ideation. CONCLUSIONS: Despite several limitations, this study has clinical implications for the development of effective strategies to mitigate suicidal ideation. In particular, effectively screening the exposure to adverse childhood experiences, early identification and treatment of depressive symptoms can play a crucial role in weakening the association between childhood adversity and suicidal ideation in older adults.


Assuntos
Experiências Adversas da Infância , Nível de Saúde , Apoio Social , Ideação Suicida , Humanos , Masculino , Feminino , República da Coreia/epidemiologia , Idoso , Experiências Adversas da Infância/psicologia , Experiências Adversas da Infância/estatística & dados numéricos , Saúde Mental , Pessoa de Meia-Idade , Depressão/psicologia , Depressão/epidemiologia , Idoso de 80 Anos ou mais
9.
Nat Commun ; 15(1): 5710, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38977711

RESUMO

Following Mycobacterium tuberculosis infection, alveolar macrophages are initially infected but ineffectively restrict bacterial replication. The distribution of M. tuberculosis among different cell types in the lung changes with the onset of T cell immunity when the dominant infected cellular niche shifts from alveolar to monocyte-derived macrophages (MDM). We hypothesize that changes in bacterial distribution among different cell types is driven by differences in T cell recognition of infected cells and their subsequent activation of antimicrobial effector mechanisms. We show that CD4 and CD8 T cells efficiently eliminate M. tuberculosis infection in alveolar macrophages, but they have less impact on suppressing infection in MDM, which may be a bacterial niche. Importantly, CD4 T cell responses enhance MDM recruitment to the lung. Thus, the outcome of infection depends on the interaction between the T cell subset and the infected cell; both contribute to the resolution and persistence of the infection.


Assuntos
Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Pulmão , Macrófagos Alveolares , Camundongos Endogâmicos C57BL , Mycobacterium tuberculosis , Mycobacterium tuberculosis/imunologia , Mycobacterium tuberculosis/fisiologia , Animais , Pulmão/microbiologia , Pulmão/imunologia , Pulmão/patologia , Macrófagos Alveolares/imunologia , Macrófagos Alveolares/microbiologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD4-Positivos/imunologia , Camundongos , Feminino , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/patologia , Macrófagos/imunologia , Macrófagos/microbiologia , Humanos
10.
Int J Mol Sci ; 25(11)2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38892302

RESUMO

Urban air pollution, a significant environmental hazard, is linked to adverse health outcomes and increased mortality across various diseases. This study investigates the neurotoxic effects of particulate matter (PM), specifically PM2.5 and PM10, by examining their role in inducing oxidative stress and subsequent neuronal cell death. We highlight the novel finding that PM increases mitochondrial ROS production via stimulating NOX4 activity, not through its expression level in Neuro-2A cells. Additionally, PMs provoke ROS production via increasing the expression and activity of NOX2 in SH-SY5Y human neuroblastoma cells, implying differential regulation of NOX proteins. This increase in mitochondrial ROS triggers the opening of the mitochondrial permeability transition pore (mPTP), leading to apoptosis through key mediators, including caspase3, BAX, and Bcl2. Notably, the voltage-dependent anion-selective channel 1 (VDAC1) increases at 1 µg/mL of PM2.5, while PM10 triggers an increase from 10 µg/mL. At the same concentration (100 µg/mL), PM2.5 causes 1.4 times higher ROS production and 2.4 times higher NOX4 activity than PM10. The cytotoxic effects induced by PMs were alleviated by NOX inhibitors GKT137831 and Apocynin. In SH-SY5Y cells, both PM types increase ROS and NOX2 levels, leading to cell death, which Apocynin rescues. Variability in NADPH oxidase sources underscores the complexity of PM-induced neurotoxicity. Our findings highlight NOX4-driven ROS and mitochondrial dysfunction, suggesting a potential therapeutic approach for mitigating PM-induced neurotoxicity.


Assuntos
Apoptose , Mitocôndrias , NADPH Oxidase 4 , Neurônios , Material Particulado , Espécies Reativas de Oxigênio , Material Particulado/toxicidade , NADPH Oxidase 4/metabolismo , NADPH Oxidase 4/genética , Espécies Reativas de Oxigênio/metabolismo , Apoptose/efeitos dos fármacos , Humanos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/patologia , Linhagem Celular Tumoral , Estresse Oxidativo/efeitos dos fármacos , Animais , Camundongos , NADPH Oxidase 2/metabolismo , NADPH Oxidase 2/genética
11.
BMJ Open ; 14(6): e073290, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38871664

RESUMO

INTRODUCTION: Despite the high prevalence of major depressive disorder (MDD) among the elderly population, the rate of treatment is low due to stigmas and barriers to medical access. Wearable devices such as smartphones and smartwatches can help to screen MDD symptoms earlier in a natural setting while forgoing these concerns. However, previous research using wearable devices has mostly targeted the younger population. By collecting longitudinal data using wearable devices from the elderly population, this research aims to produce prediction algorithms for late-life depression and to develop strategies that strengthen medical access in community care systems. METHODS AND ANALYSIS: The current cohort study recruited a subsample of 685 elderly people from the Korean Genome and Epidemiology Study-Cardiovascular Disease Association Study, a national large cohort established in 2004. The current study has been conducted over a 3-year period to explore the development patterns of late-life depression. Participants have completed three annual face-to-face interviews (baseline, the first follow-up and the second follow-up) and 2 years of app-based surveys and passive sensing data collection. All the data collection will end at the second follow-up interview. The collected self-report, observational and passive sensing data will be primarily analysed by machine learning. ETHICS AND DISSEMINATION: This study protocol has been reviewed and approved by the Yonsei University Mirae Campus Institutional Review Board (1041849-2 02 111 SB-180-06) in South Korea. All participants provided written informed consent. The findings of this research will be disseminated by academic publications and conference presentations.


Assuntos
Algoritmos , Transtorno Depressivo Maior , Dispositivos Eletrônicos Vestíveis , Humanos , Idoso , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/epidemiologia , República da Coreia/epidemiologia , Masculino , Feminino , Estudos de Coortes , Projetos de Pesquisa , Aprendizado de Máquina , Idoso de 80 Anos ou mais
12.
Clin Transplant Res ; 38(2): 98-105, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38895774

RESUMO

Background: Kidney transplantation (KT) improves physical and psychological prognoses for patients with end-stage kidney disease (ESKD). However, few comparative studies have examined depression and suicide rates among patients with ESKD treated with dialysis versus KT. Methods: Data on 21,809 patients with ESKD were extracted from the Korean National Health Insurance Service database, extending from January 2002 to December 2018. These patients exhibited no history of depression or insomnia before starting renal replacement therapy. Outcomes were compared between dialysis and KT recipients using 1:2 propensity score matching (PSM). Results: Of the patients, 17,649 received dialysis (hemodialysis, 15,537; peritoneal dialysis, 2,112), while 4,160 underwent KT. Of those on dialysis, 45.04% (7,949) experienced insomnia, compared to 25.72% (1,070) of KT recipients (P<0.001). Depression was more frequent among dialysis recipients (22.77%, 4,019) than KT recipients (8.61%, 358; P<0.001). Additionally, those on dialysis had a higher incidence of suicide (0.19%, 33) than recipients of KT (0.12%, 5; P=0.047). After PSM, the hazard ratio (HR) for depression in patients on dialysis compared to KT recipients was 1.76 (95% confidence interval [CI], 1.56-1.99). In subgroup analysis, the relative likelihood of depression among dialysis recipients was particularly high for residents of urban areas (HR, 2.10; 95% CI, 1.80-2.44) and patients under 65 years old (HR, 1.82; 95% CI, 1.62-2.09). Conclusions: KT recipients exhibit a lower suicide rate than patients on dialysis. Furthermore, KT is associated with a lower prevalence of depression among Korean patients with ESKD, particularly urban residents and individuals under 65 years old.

13.
Nutr Metab (Lond) ; 21(1): 33, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38858757

RESUMO

BACKGROUND: Hyperuricemia could be a risk for various chronic diseases, and it could be largely corrected by diet control. This study was a nationwide cross-sectional study to investigate the association between serum uric acid level and dietary fiber intake. METHODS: This study analyzed data based on the Korean National Health and Nutrition Examination Survey conducted from 2016 to 2018. Adults over 20 years of age with normal renal function, defined as an estimated glomerular filtration rate (eGFR) over 30mL/min/1.73m2, were included. The criteria for hyperuricemia were ≥ 7 mg/dL in men and ≥ 6 mg/dL in women. Data regarding dietary intake were obtained using the 24-hour recall method. RESULTS: A total of 15,278 subjects (6,455 males/8,823 females) were analyzed. The prevalence of hyperuricemia was 19.3% in men and 6.8% in women. There were significant, negative associations between serum uric acid and total fiber intake in both men and women. Consuming more than 27.9 g of dietary fiber in men and 20.7 g in women reduced the risk of hyperuricemia by approximately 30% with odds ratios of 0.72 (0.62-0.83) and 0.71 (0.56-0.88) in men and women, respectively. With regard to the risk reduction by the type of dietary fiber, cereal fiber was significantly identified in both men and women, while fruit fiber was only significant in men. In the subgroup analysis, this association remained significantly in young and metabolically healthy populations with normal weight. CONCLUSIONS: Dietary fiber intake was inversely associated with serum uric acid levels. This relationship was particularly significant in metabolically healthy young adults.

14.
Arch Pharm Res ; 47(5): 465-480, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38734854

RESUMO

Tumor necrosis factor alpha (TNF-α), an abundant inflammatory cytokine in the tumor microenvironment (TME), is linked to breast cancer growth and metastasis. In this study, we established MCF10A cell lines incubated with TNF-α to investigate the effects of continuous TNF-α exposure on the phenotypic change of normal mammary epithelial cells. The established MCF10A-LE cell line, through long-term exposure to TNF-α, displayed cancer-like features, including increased proliferation, migration, and sustained survival signaling even in the absence of TNF-α stimulation. Unlike the short-term exposed cell line MCF10A-SE, MCF10A-LE exhibited elevated levels of epidermal growth factor receptor (EGFR) and subsequent TNF receptor 2 (TNFR2), and silencing of EGFR or TNFR2 suppressed the cancer-like phenotype of MCF10A-LE. Notably, we demonstrated that the elevated levels of NAD(P)H oxidase 4 (NOX4) and the resulting increase in reactive oxygen species (ROS) were associated with EGFR/TNFR2 elevation in MCF10A-LE. Furthermore, mammosphere-forming capacity and the expression of cancer stem cell (CSC) markers increased in MCF10A-LE. Silencing of EGFR reversed these effects, indicating the acquisition of CSC-like properties via EGFR signaling. In conclusion, our results reveal that continuous TNF-α exposure activates the EGFR/TNFR2 signaling pathway via the NOX4/ROS axis, promoting neoplastic changes in mammary epithelial cells within the inflammatory TME.


Assuntos
Neoplasias da Mama , Células Epiteliais , Receptores ErbB , Fenótipo , Receptores Tipo II do Fator de Necrose Tumoral , Fator de Necrose Tumoral alfa , Humanos , Receptores Tipo II do Fator de Necrose Tumoral/metabolismo , Receptores ErbB/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Feminino , Células Epiteliais/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Proliferação de Células/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , NADPH Oxidase 4/metabolismo , NADPH Oxidase 4/genética , Movimento Celular/efeitos dos fármacos , Glândulas Mamárias Humanas/metabolismo , Glândulas Mamárias Humanas/patologia , Glândulas Mamárias Humanas/efeitos dos fármacos , Microambiente Tumoral , Células-Tronco Neoplásicas/patologia , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/efeitos dos fármacos , Linhagem Celular Tumoral
16.
Nat Commun ; 15(1): 2732, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38548760

RESUMO

Fe‒S cluster-harboring enzymes, such as carbon monoxide dehydrogenases (CODH), employ sophisticated artificial electron mediators like viologens to serve as potent biocatalysts capable of cleaning-up industrial off-gases at stunning reaction rates. Unraveling the interplay between these enzymes and their associated mediators is essential for improving the efficiency of CODHs. Here we show the electron mediator-interaction site on ChCODHs (Ch, Carboxydothermus hydrogenoformans) using a systematic approach that leverages the viologen-reactive characteristics of superficial aromatic residues. By enhancing mediator-interaction (R57G/N59L) near the D-cluster, the strategically tailored variants exhibit a ten-fold increase in ethyl viologen affinity relative to the wild-type without sacrificing the turn-over rate (kcat). Viologen-complexed structures reveal the pivotal positions of surface phenylalanine residues, serving as external conduits for the D-cluster to/from viologen. One variant (R57G/N59L/A559W) can treat a broad spectrum of waste gases (from steel-process and plastic-gasification) containing O2. Decoding mediator interactions will facilitate the development of industrially high-efficient biocatalysts encompassing gas-utilizing enzymes.


Assuntos
Elétrons , Complexos Multienzimáticos , Complexos Multienzimáticos/química , Aldeído Oxirredutases/genética , Aldeído Oxirredutases/química , Gases , Viologênios , Monóxido de Carbono/química
17.
Small ; 20(34): e2400333, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38528427

RESUMO

Redox-active organic compounds gather significant attention for their potential application as electrodes in alkali ion batteries, owing to the structural versatility, environmental friendliness, and cost-effectiveness. However, their practical applications of such compounds are impeded by insufficient active sites with limited capacity, dissolution in electrolytes, and sluggish kinetics. To address these issues, a naphthol group-containing triarylamine polymer, namely poly[6,6'-(phenylazanediyl)bis(naphthol)] (poly(DNap-OH)) is rationally designed and synthesized, via oxidative coupling polymerization. It is capable of endowing favorable steric structures that facilitate fast ion diffusion, excellent chemical stability in organic electrolytes, and additional redox-active sites that enable a bipolar redox reaction. By exploiting these advantages, poly(DNap-OH) cathodes demonstrate remarkable cycling stability in both lithium-ion batteries (LIBs) and potassium-ion batteries (PIBs), showcasing enhanced specific capacity and redox reaction kinetics in comparison to the conventional poly(4-methyltriphenylamine) cathodes. Overall, this work offers insights into molecular design strategies for the development of high-performance organic cathodes in alkali-ion batteries.

18.
Breast Cancer Res ; 26(1): 31, 2024 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-38395930

RESUMO

BACKGROUND: Accurate classification of breast cancer molecular subtypes is crucial in determining treatment strategies and predicting clinical outcomes. This classification largely depends on the assessment of human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), and progesterone receptor (PR) status. However, variability in interpretation among pathologists pose challenges to the accuracy of this classification. This study evaluates the role of artificial intelligence (AI) in enhancing the consistency of these evaluations. METHODS: AI-powered HER2 and ER/PR analyzers, consisting of cell and tissue models, were developed using 1,259 HER2, 744 ER, and 466 PR-stained immunohistochemistry (IHC) whole-slide images of breast cancer. External validation cohort comprising HER2, ER, and PR IHCs of 201 breast cancer cases were analyzed with these AI-powered analyzers. Three board-certified pathologists independently assessed these cases without AI annotation. Then, cases with differing interpretations between pathologists and the AI analyzer were revisited with AI assistance, focusing on evaluating the influence of AI assistance on the concordance among pathologists during the revised evaluation compared to the initial assessment. RESULTS: Reevaluation was required in 61 (30.3%), 42 (20.9%), and 80 (39.8%) of HER2, in 15 (7.5%), 17 (8.5%), and 11 (5.5%) of ER, and in 26 (12.9%), 24 (11.9%), and 28 (13.9%) of PR evaluations by the pathologists, respectively. Compared to initial interpretations, the assistance of AI led to a notable increase in the agreement among three pathologists on the status of HER2 (from 49.3 to 74.1%, p < 0.001), ER (from 93.0 to 96.5%, p = 0.096), and PR (from 84.6 to 91.5%, p = 0.006). This improvement was especially evident in cases of HER2 2+ and 1+, where the concordance significantly increased from 46.2 to 68.4% and from 26.5 to 70.7%, respectively. Consequently, a refinement in the classification of breast cancer molecular subtypes (from 58.2 to 78.6%, p < 0.001) was achieved with AI assistance. CONCLUSIONS: This study underscores the significant role of AI analyzers in improving pathologists' concordance in the classification of breast cancer molecular subtypes.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/metabolismo , Receptores de Estrogênio/metabolismo , Biomarcadores Tumorais/metabolismo , Inteligência Artificial , Variações Dependentes do Observador , Receptores de Progesterona/metabolismo , Receptor ErbB-2/metabolismo
19.
J Cosmet Dermatol ; 23(6): 2066-2077, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38411029

RESUMO

BACKGROUND: Recommendations for cosmetics are gaining popularity, but they are not being made with consideration of the analysis of cosmetic ingredients, which customers consider important when selecting cosmetics. AIMS: This article aims to propose a method for estimating the efficacy of cosmetics based on their ingredients and introduces a system that recommends personalized products for consumers, combined with AI skin analysis. METHODS: We constructed a deep neural network architecture to analyze sequentially arranged cosmetic ingredients in the product and incorporated skin analysis models to get the precise skin status of users from frontal face images. Our recommendation system makes decisions based on the results optimized for the individual. RESULTS: Our cosmetic recommendation system has shown its effectiveness through reliable evaluation metrics, and numerous examples have demonstrated its ability to make reasonable recommendations for various skin problems. CONCLUSION: The result shows that deep learning methods can be used to predict the effects of products based on their cosmetic ingredients and are available for use in personalized cosmetic recommendations.


Assuntos
Cosméticos , Aprendizado Profundo , Face , Higiene da Pele , Humanos , Cosméticos/administração & dosagem , Cosméticos/química , Higiene da Pele/métodos , Pele/efeitos dos fármacos , Dermatopatias
20.
BMJ Open Diabetes Res Care ; 12(1)2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38413174

RESUMO

INTRODUCTION: Diabetes mellitus is known to increase the risk of cancer. Fasting blood glucose (FBG) levels can be changed over time. However, the association between FBG trajectory and cancer risk has been insufficiently studied. This research aims to examine the relationship between FBG trajectories and cancer risk in the Korean population. RESEARCH DESIGN AND METHODS: We analyzed data from the National Health Insurance Service-National Health Screening Cohort collected between 2002 and 2015. Group-based trajectory modeling was performed on 256,271 Koreans aged 40-79 years who had participated in health examinations at least three times from 2002 to 2007. After excluding patients with cancer history before 2008, we constructed a cancer-free cohort. The Cox proportional hazards model was applied to examine the association between FBG trajectories and cancer incidence by cancer type, after adjustments for covariates. Cancer case was defined as a person who was an outpatient thrice or was hospitalized once or more with a cancer diagnosis code within the first year of the claim. RESULTS: During the follow-up time (2008-2015), 18,991 cancer cases were identified. Four glucose trajectories were found: low-stable (mean of FBG at each wave <100 mg/dL), elevated-stable (113-124 mg/dL), elevated-high (104-166 mg/dL), and high-stable (>177 mg/dL). The high-stable group had a higher risk of multiple myeloma, liver cancer and gastrointestinal cancer than the low-stable group, with HR 4.09 (95% CI 1.40 to 11.95), HR 1.68 (95% CI 1.25 to 2.26) and HR 1.27 (95% CI 1.11 to 1.45), respectively. In elevated-stable trajectory, the risk increased for all cancer (HR 1.08, 95% CI 1.02 to 1.16) and stomach cancer (HR 1.24, 95% CI 1.07 to 1.43). Significant associations were also found in the elevated-high group with oral (HR 2.13, 95% CI 1.01 to 4.47), liver (HR 1.50, 95% CI 1.08 to 2.08) and pancreatic cancer (HR 1.99, 95% CI 1.20 to 3.30). CONCLUSIONS: Our study highlights that the uncontrolled high glucose level for many years may increase the risk of cancer.


Assuntos
Diabetes Mellitus , Neoplasias , Humanos , Glicemia , Estudos de Coortes , Jejum , Diabetes Mellitus/diagnóstico , Neoplasias/epidemiologia
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