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Background: Evaluating cardiovascular risk in patients experiencing acute ST-elevation myocardial infarction (STEMI) and undergoing percutaneous coronary intervention (PCI) is crucial for early intervention and improving long-term outcomes. 24â h Holter monitoring provides continuous cardiac electrophysiological data, enabling the detection of arrhythmias and autonomic dysfunction that are not captured during routine examinations. This study aimed to examine the relationship between Holter monitoring metrics and the occurrence of out-of-hospital major adverse cardiovascular events (MACEs) following PCI in patients with STEMI, offering insights into cardiovascular risk evaluation. Methods: This prospective cohort study included STEMI patients undergoing PCI. 24â h Holter monitoring data were recorded, including heart rate, heart rate variability (HRV) metrics such as SDNN and SDANN index, heart rate deceleration capacity (DC) at different time scales (DC2, DC4, DC8), and the frequency of premature ventricular contractions (PVCs). Independent correlations between these indices and MACEs, as well as cardiovascular deaths, were investigated using multifactorial logistic regression. Predictive capacities were assessed through receiver operating characteristic (ROC) curves. Results: A total of 172 participants were enrolled in this study. Over the 3-year follow-up period, MACEs were observed in 57 patients, including 20 cases of cardiac death. In logistic regression models adjusted for confounding variables, SDNN [OR: 0.980; 95% CI: (0.967, 0.994); p = 0.005] and SDANN index [OR: 0.982; 95% CI: (0.969, 0.996); p = 0.009] were negatively associated with the incidence of MACEs. Conversely, the slowest heart rate [OR: 1.075; 95% CI: (1.022, 1.131); p = 0.005] and frequent PVCs [OR: 2.685; 95% CI: (1.204, 5.987); p = 0.016] demonstrated a positive association with MACEs. Furthermore, SDNN [OR: 0.957; 95% CI: (0.933, 0.981); p = 0.001], DC [OR: 0. 702; 95% CI: (0.526, 0.938); p = 0.017]) and DC4 [OR: 0.020; 95% CI: (0.001, 0.664); p = 0.029] were negatively associated with cardiac death. The ROC analysis results indicated that SDNN was an effective predictor of both MACEs [AUC: 0.688 (95% CI: 0.601-0.776)] and cardiac death [AUC: 0.752 (95% CI: 0.625-0.879)]. Conclusion: HRV, DC metrics, and frequent PVCs obtained by 24â h Holter monitoring were associated with the risk of MACEs in STEMI patients. These metrics can help clinicians identify at-risk patients early so that timely interventions.
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Exposure of metals to neutron irradiation results in an increase in the yield strength and a significant loss of ductility. Irradiation hardening is also closely related to the fracture toughness temperature shift or the ductile-to-brittle transition temperature (DBTT) shift in alloys with a body-centered cubic (bcc) crystal structure. Ion irradiation is an indispensable tool in the study of the radiation effects of materials for nuclear energy systems. Due to the shallow damage depth in ion-irradiated materials, the nanoindentation test is the most commonly used method for characterizing the changes in mechanical properties after ion irradiation. Issues that affect the analysis of irradiation hardening may arise due to changes in the surface morphology and mechanical properties, as well as the inherent complexities in nanoscale indentation. These issues, including changes in surface roughness, carbon contamination, the pile-up effect, and the indentation size effect, with corresponding measures, were reviewed. Modeling using the crystal plasticity finite element method of the nanoindentation of ion-irradiated materials was also reviewed. The challenges in extending the nanoindentation test to high temperatures and to multiscale simulation were addressed.
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OBJECTIVE: To assess the association of -c.108C>T and c.192Q>R polymorphisms of paraoxonase 1 (PON1) gene with preeclampsia (PE) and the influence of genotypes on the metabolic and oxidative stress indexes among Chinese women. METHODS: This case-control study has included 334 patients with PE and 1337 healthy pregnant women. The -c.108C>T and c.192Q>R genotypes were determined by PCR and restriction fragment length polymorphism method. Metabolic and oxidative stress parameters were also analyzed. RESULTS: No statistical difference in the genotypic and allelic frequencies for the -c.108C>T and c.192Q>R polymorphisms of the PON1 gene was found between the PE patients and the healthy controls (P > 0.05). Nevertheless, the 192Q-108T haplotype of these polymorphisms was associated with an increased risk of PE (P = 0.007). Total antioxidant capacity (TAC) and atherosderosis index were higher in patients with the -108TT genotype compared with those with a CT genotype (P < 0.05); whilst total oxidant status was lower in patients with a CT genotype compared with those with a CC genotype (P = 0.036). Malondialdehyde level was higher in patients with a 192RR genotype compared with those with a QQ genotype (P = 0.019). TAC level was higher in patients with a RR genotype compared with those with a QR genotype (P = 0.015). CONCLUSION: The 192Q-108T haplotype of the PON1 gene is associated with the risk for PE. These polymorphisms may be associated with abnormal lipid metabolism and oxidative stress among Chinese PE patients.
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Arildialquilfosfatase , Povo Asiático , Pré-Eclâmpsia , Adulto , Feminino , Humanos , Gravidez , Adulto Jovem , Arildialquilfosfatase/genética , Povo Asiático/genética , Estudos de Casos e Controles , China , População do Leste Asiático , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Estresse Oxidativo , Polimorfismo de Nucleotídeo Único , Pré-Eclâmpsia/genéticaRESUMO
BACKGROUND: T-cell responses can be protective or detrimental during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection; however, the underlying mechanism is poorly understood. METHODS: In this study, we screened 144 15-mer peptides spanning the SARS-CoV-2 spike, nucleocapsid (NP), M, ORF8, ORF10, and ORF3a proteins and 39 reported SARS-CoV-1 peptides in peripheral blood mononuclear cells (PBMCs) from nine laboratory-confirmed coronavirus disease 2019 (COVID-19) patients (five moderate and four severe cases) and nine healthy donors (HDs) collected before the COVID-19 pandemic. T-cell responses were monitored by IFN-γ and IL-17A production using ELISA, and the positive samples were sequenced for the T cell receptor (TCR) ß chain. The positive T-cell responses to individual SARS-CoV-2 peptides were validated by flow cytometry. RESULTS: COVID-19 patients with moderate disease produced more IFN-γ than HDs and patients with severe disease (moderate vs. HDs, p < 0.0001; moderate vs. severe, p < 0.0001) but less IL-17A than those with severe disease (p < 0.0001). A positive correlation was observed between IFN-γ production and T-cell clonal expansion in patients with moderate COVID-19 (r = 0.3370, p = 0.0214) but not in those with severe COVID-19 (r = -0.1700, p = 0.2480). Using flow cytometry, we identified that a conserved peptide of the M protein (Peptide-120, P120) was a dominant epitope recognized by CD8+ T cells in patients with moderate disease. CONCLUSION: Coordinated IFN-γ production and clonal expansion of SARS-CoV-2-specific T cells are associated with disease resolution in COVID-19. Our findings contribute to a better understanding of T-cell-mediated immunity in COVID-19 and may inform future strategies for managing and preventing severe outcomes of SARS-CoV-2 infection.
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COVID-19 , Mapeamento de Epitopos , Epitopos de Linfócito T , Interferon gama , SARS-CoV-2 , Humanos , Interferon gama/imunologia , Interferon gama/metabolismo , COVID-19/imunologia , COVID-19/virologia , Epitopos de Linfócito T/imunologia , SARS-CoV-2/imunologia , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Interleucina-17/imunologia , Interleucina-17/metabolismo , Idoso , Linfócitos T/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Linfócitos T CD8-Positivos/imunologiaRESUMO
OBJECTIVE: This study aimed to identify the potential subgroups of migraines based on the patterns of migraine associated symptoms, vestibular and auditory symptoms using latent class analysis and to explore their characteristics. METHOD: A total of 555 patients with migraine participated in the study. Symptoms such as nausea, vomiting, photophobia, phonophobia, osmophobia, visual symptoms, vestibular symptoms (dizziness, vertigo), and auditory symptoms (tinnitus, hearing loss, aural fullness) were assessed. Latent class analysis was performed to identify subgroups of migraines. Covariates such as gender, age of migraine onset, frequency of migraine attacks per month, and family history were also considered. RESULTS: The analysis revealed four latent classes: the Prominent Vestibular; Prominent Nausea; Presenting Symptoms but not prominent or dominant; and Sensory Hypersensitivity groups. Various covariates, such as gender, age of migraine onset, and frequency of migraine attacks, demonstrated significant differences among the four groups. The Sensory Hypersensitivity group showed the presence of multiple sensory symptoms, earlier age of migraine onset, and higher proportion of females. The Prominent Vestibular group had the highest probability of dizziness or vertigo but lacked the presence of auditory symptoms. The Prominent Nausea group exhibited prominent nausea. The Presenting Symptoms but not prominent or dominant group comprised individuals with the highest migraine attacks per month and proportion of chronic migraine. CONCLUSION: This study identifies four subgroups of migraines based on the patterns of symptoms. The findings suggest potential different but overlapped mechanisms behind the vestibular and auditory symptoms of migraine. Considering the different patterns of migraine-related symptoms may provide deeper insights for patients' prognosis and clinical decision-making.
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Análise de Classes Latentes , Transtornos de Enxaqueca , Humanos , Transtornos de Enxaqueca/diagnóstico , Transtornos de Enxaqueca/epidemiologia , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Vertigem/diagnóstico , Vertigem/epidemiologia , Adulto Jovem , Náusea/epidemiologia , Náusea/etiologia , Náusea/diagnóstico , Tontura/epidemiologia , Tontura/diagnóstico , Idoso , Adolescente , Doenças Vestibulares/diagnóstico , Doenças Vestibulares/epidemiologia , Doenças Vestibulares/complicaçõesRESUMO
Metal-organic frameworks (MOFs) are porous materials resulting from the coordination of metal clusters or ions with organic ligands, merging macromolecular and coordination chemistry features. Among these, zeolitic imidazolate framework-8 (ZIF-8) stands out as a widely utilized MOF known for its robust stability in aqueous environments owing to the robust interaction between its constituent zinc ions (Zn2+) and 2-methylimidazole (2-MIM). ZIF-8 readily decomposes under acidic conditions, serving as a promising candidate for pH-responsive drug delivery systems. Moreover, biomimetic materials typically possess good biocompatibility, reducing immune reactions. By mimicking natural structures or surface features within the body, they enhance the targeting of nanoparticles, prolong their circulation time, and increase their bioavailability in vivo. This review explores the latest advancements in biomimetic ZIF-8 nanoparticles for drug delivery, elucidating the primary obstacles and future prospects in utilizing ZIF-8 for drug delivery applications.
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Materiais Biomiméticos , Sistemas de Liberação de Medicamentos , Imidazóis , Estruturas Metalorgânicas , Nanopartículas , Zeolitas , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacocinética , Humanos , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacocinética , Zeolitas/química , Zeolitas/farmacocinética , Nanopartículas/química , Sistemas de Liberação de Medicamentos/métodos , Imidazóis/química , Imidazóis/farmacocinética , Imidazóis/administração & dosagem , Animais , Zinco/química , Zinco/farmacocinética , Zinco/administração & dosagem , Biomimética/métodos , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Concentração de Íons de HidrogênioRESUMO
Methanogenic archaea, characterized by their cell membrane lipid molecules consisting of isoprenoid chains linked to glycerol-1-phosphate via ether bonds, exhibit exceptional adaptability to extreme environments. However, this distinct lipid architecture also complicates the interactions between methanogenic archaea and nanoparticles. This study addresses this challenge by exploring the interaction and transformation of selenium nanoparticles (SeNPs) within archaeal Methanosarcina acetivorans C2A. We demonstrated that the effects of SeNPs are highly concentration-dependent, with chemical stimulation of cellular processes at lower SeNPs concentrations as well as oxidative stress and metabolic disruption at higher concentrations. Notably, we observed the formation of a protein corona on SeNPs, characterized by the selective adsorption of enzymes critical for methylotrophic methanogenesis and those involved in selenium methylation, suggesting potential alterations in protein function and metabolic pathways. Furthermore, the intracellular transformation of SeNPs into both inorganic and organic selenium species highlighted their bioavailability and dynamic transformation within archaea. These findings provide vital insights into the nano-bio interface in archaeal systems, contributing to our understanding of archaeal catalysis and its broader applications.
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Methanosarcina , Nanopartículas , Selênio , Selênio/química , Selênio/metabolismo , Methanosarcina/metabolismo , Nanopartículas/química , Nanopartículas/metabolismo , Estresse OxidativoRESUMO
OBJECTIVE: Our research aimed to investigate the therapeutic effects of Tubastatin-A, a glucocorticoid receptor (GR) mitochondrial translocation inhibitor, and mitoquinone (MitoQ), an antioxidant, on attenuating dexamethasone (DEX)-induced macrophage apoptosis. METHODS: We treated RAW264.7 macrophages with different combinations of DEX and either Tubastatin-A or MitoQ. Parameters such as mitochondrial GR translocation, mitochondrial reactive oxygen species levels, mitochondrial membrane potential, mitochondrial permeability transition pore opening, cytochrome C efflux to the cytosol, and apoptosis were subsequently evaluated in the different treatment groups via qRT-PCR, western blotting, and immunofluorescence assays. RESULTS: DEX intervention increased the translocation of GRs into the mitochondria, while reducing the expression of the mitochondrial gene MT-CO1 and the activity of mitochondrial respiratory chain complex IV in macrophages. In addition, DEX administration increased mtROS levels, mitochondrial permeability transition pore opening, and mitochondrial cytochrome C release in macrophages, which promoted their apoptosis. We found that Tubastatin-A inhibited mitochondrial GR translocation and reversed the DEX-induced increase in GR levels within the mitochondria. Furthermore, Tubastatin-A mitigated various mitochondrial changes induced by DEX, including reducing the efflux of mitochondrial cytochrome C and inhibiting macrophage apoptosis. Similarly, MitoQ exerted its effects on macrophage apoptosis by reducing mtROS levels through the mitochondrial pathway. CONCLUSIONS: The DEX-mediated translocation of GR into mitochondria disrupts the mitochondrial function of macrophages, which induces their apoptosis. By inhibiting mitochondrial translocation of GR and reducing mtROS levels, Tubastatin-A and MitoQ can effectively attenuate macrophage apoptosis, which has clinical implications for reducing the notable side effects associated with glucocorticoid use.
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Apoptose , Dexametasona , Glucocorticoides , Macrófagos , Mitocôndrias , Receptores de Glucocorticoides , Receptores de Glucocorticoides/metabolismo , Animais , Camundongos , Apoptose/efeitos dos fármacos , Células RAW 264.7 , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Dexametasona/farmacologia , Glucocorticoides/farmacologia , Transporte Proteico/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Ubiquinona/farmacologia , Ubiquinona/análogos & derivados , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Compostos OrganofosforadosRESUMO
Enhancing the thermoelectric performance of n-type polycrystalline SnSe is essential, addressing challenges posed by elevated thermal conductivity and compromised power factor inherent in its intrinsic p-type characteristics. This investigation utilized solid-state reactions and spark plasma sintering techniques for the synthesis of n-type SnSe. A significant improvement in the figure of merit (ZT) is achieved through strategic reduction in Se concentration and optimization of crystal orientation. The co-doping with Br and Ge further improves the material; Br amplifies carrier concentration, enhancing electrical conductivity, while Ge introduces effective phonon scattering centers. In the Br/Ge co-doped SnSe sample, thermal conductivity dropped to 0.38 Wm⻹K⻹, yielding a remarkable power factor of 662 µW mK- 2 at 773 K, culminating in a ZT of 1.34. This signifies a noteworthy 605% improvement over the pristine sample, underscoring the pivotal role of Ge doping in enhancing n-type material thermoelectric properties. The enhancement is attributed to Br doping introducing additional electronic states near the valence band, and Ge doping modifying the band structure, fostering resonant states near the conduction band. The Br/Ge co-doping further transforms the band structure, influencing electrical conductivity, Seebeck coefficient, and thermal conductivity, advancing the understanding and application of n-type SnSe materials for superior thermoelectric performance.
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Microglia are resident macrophages within the central nervous system, serving as the first responders to neuroinflammation. Glucocorticoids (GCs) may cause damage to brain tissue, but the specific mechanism remains unclear. This study was divided into two parts: a glucocorticoid receptor (GR) mitochondrial translocation intervention experiment and a mitochondrial oxidative stress inhibition experiment. BV-2 microglia were stimulated with dexamethasone (DEX) and treated with either tubastatin-A or mitoquinone (MitoQ) for 24 h. Our results showed that DEX increased the translocation of GRs to mitochondria, and this effect was accompanied by decreases in the expression of mitochondrially encoded cytochrome c oxidase 1 (MT-CO1) and mitochondrially encoded cytochrome c oxidase 3 (MT-CO3) and increases in the expression of NOD-like receptor thermal protein domain-associated protein 3 (NLRP3), caspase-1, and Gasdermin D (GSDMD). The level of mitochondrial respiratory chain complex IV (MRCC IV) and adenosine triphosphate (ATP) was decreased. An elevation in the level of mitochondrial oxidative stress and the opening of the mitochondrial permeability transition pore (mPTP) was also observed. Mechanistically, tubastatin-A significantly suppressed the mitochondrial translocation of GRs, improved the expression of mitochondrial genes, promoted the restoration of mitochondrial function, and inhibited pyroptosis. MitoQ significantly prevented mitochondrial oxidative stress, improved mitochondrial function, and reduced apoptosis and pyroptosis. Both tubastatin-A and MitoQ suppressed DEX-induced pyroptosis. This study substantiates that the increase in the mitochondrial translocation of GRs mediated by GCs exacerbates oxidative stress and pyroptosis in microglia, which indicates that the regulation of mitochondrial pathways by GCs is pathogenic to microglia.
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Glucocorticoides , Piroptose , Glucocorticoides/farmacologia , Glucocorticoides/metabolismo , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismo , Microglia/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Estresse Oxidativo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismoRESUMO
Background: Recurrence following radical resection in patients with stage IB gastric cancer (GC) is not uncommon. However, whether postoperative adjuvant chemotherapy could reduce the risk of recurrence in stage IB GC remains contentious. Methods: We collected data on 2110 consecutive patients with pathologic stage IB (T1N1M0 or T2N0M0) GC who were admitted to 8 hospitals in China from 2009 to 2018. The survival of patients who received adjuvant chemotherapy was compared with that of postoperative observation patients using propensity score matching (PSM). Two survival prediction models were constructed to estimate the predicted net survival gain attributable to adjuvant chemotherapy. Findings: Of the 2110 patients, 1344 received adjuvant chemotherapy and 766 received postoperative observation. Following the 1-to-1 matching, PSM yielded 637 matched pairs. Among matched pairs, adjuvant chemotherapy was not associated with improved survival compared with postoperative observation (OS: hazard ratio [HR], 0.72; 95% CI, 0.52-1.00; DFS: HR, 0.91; 95% CI, 0.64-1.29). Interestingly, in the subgroup analysis, reduced mortality after adjuvant chemotherapy was observed in the subgroups with elevated serum CA19-9 (HR, 0.22; 95% CI, 0.08-0.57; P = 0.001 for multiplicative interaction), positive lymphovascular invasion (HR, 0.32; 95% CI, 0.17-0.62; P < 0.001 for multiplicative interaction), or positive lymph nodes (HR, 0.17; 95% CI, 0.07-0.38; P < 0.001 for multiplicative interaction). The survival prediction models mainly based on variables associated with chemotherapy benefits in the subgroup analysis demonstrated good calibration and discrimination, with relatively high C-indexes. The C-indexes for OS were 0.74 for patients treated with adjuvant chemotherapy and 0.70 for patients treated with postoperative observation. Two nomograms were built from the models that can calculate individualized estimates of expected net survival gain attributable to adjuvant chemotherapy. Interpretation: In this cohort study, pathologic stage IB alone was not associated with survival benefits from adjuvant chemotherapy compared with postoperative observation in patients with early-stage GC. High-risk clinicopathologic features should be considered simultaneously when evaluating patients with stage IB GC for adjuvant chemotherapy. Funding: National Natural Science Foundation of China; the National Key R&D Program of China.
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BACKGROUND: Although neuromyelitis optica spectrum disorder (NMOSD) has high recurrence and disability rates, cases of relapses can be recognized, and timely intervention can be provided if the risk of relapse is properly perceived. However, there have been no studies to explore patients' perceptions of recurrence risk and coping strategies. This study aimed to explore the characteristics of relapse risk perception and coping strategies of patients with NMOSD. METHODS: We adopted the phenomenological method of qualitative research. Face-to-face, semi-structured in-depth interviews were conducted with 15 patients with NMOSD. The interview data were then analyzed using the Colaizzi seven-step analysis. RESULTS: The analysis revealed five major themes. The first theme was the 'perception of possibility of relapse', which included subjectively underestimating the likelihood of relapse and shifted from underestimation to overestimation; the second theme was 'relapse warning signs perception'; the third theme was 'perception of relapse triggers', which included understanding relapse triggers, potential misconceptions about relapse triggers, and no identifiable cause of recurrence; the fourth theme was 'perception of the relapse consequences', encompassing severe impairment of body structure and function, prominent psychological problems, limited family roles and social functions, and heavy financial burden; and the final theme was 'relapse risk coping strategies', which included actively yearning for and seeking information support, recurrence risk prevention/management, limitations of coping strategies. CONCLUSIONS: This study's findings revealed that newly diagnosed patients as well as those who relapsed subjectively underestimated the likelihood of relapse before they had experienced multiple (two or more) relapses. In contrast, patients who had experienced multiple relapses had transitioned from initial underestimation to subsequent overestimation. Additionally, patients' compliance with medication was identified as a relapse-risk behaviors that was very manageable. The occurrence of relapse is associated with significant and extensive adverse effects on patients. Consequently, patients are eager to communicate with their healthcare providers regarding treatment planning and relapse management.
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Neuromielite Óptica , Humanos , Neuromielite Óptica/tratamento farmacológico , Capacidades de Enfrentamento , Recidiva , Pesquisa Qualitativa , Percepção , Estudos Retrospectivos , Aquaporina 4RESUMO
Objective: To investigate the ï¼75 G/A single-nucleotide polymorphism in the promoter region of apolipoprotein A1 gene (apoA1) and its association with gestational diabetes mellitus (GDM) in pregnant women and to provide references for the exploration in the molecular genetic basis of GDM. Methods: A total of 626 GDM patients and 1022 normal pregnant women, ie, the controls, were included in the study. The genotyping of apoA1 ï¼75 G/A polymorphism was performed by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis. Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and glucose (Glu) were measured by enzymatic methods. Plasma insulin (INS) was measured by chemiluminescence immunoassay. The protein levels of apoA1 and apoB were measured by the turbidimetric immunoassay. Results: Allele frequencies of G and A were 0.718 and 0.282 in the GDM group and 0.713 and 0.287 in the control group, respectively. Distribution of the genotype frequencies was found to be in Hardy-Weinberg equilibrium in both the GDM and control groups. There was no significant difference in the frequencies of alleles G and A and the genotypes of apoA1 ï¼75 G/A polymorphism between the GDM and the control group (P>0.05). In the GDM group, the carriers with the genotype AA were associated with significantly higher levels of TC, HDL-C, and apoA1 than those with genotypes GG and GA did (all P<0.05). After the GDM patients were divided into obese and non-obese subgroups, the genotype-related apoA1 variation was observed only in obese patients, while the genotype-related TC and HDL-C variations were evident in non-obese patients (P<0.05). In the control group, carriers of genotypes AA and GA had higher systolic blood pressure (SBP) and HDL-C than the carriers of genotype GG did (all P<0.05). Carriers of genotypes AA had significantly lower Glu levels than carriers of genotypes GG and GA did (P<0.05). The control subjects were further divided into subgroups according to their body mass index (BMI). Analysis of the subgroups showed that AA carriers were associated with higher SBP levels in the obese control women only, while lower Glu levels were evident in both obese and non-obese control women. Conclusion: These results suggest that ï¼75 G/A polymorphism in the apoA1 gene is not associated with GDM. However, the genetic variation is closed associated with the plasma apoA1, HDL-C, and TC levels in GDM patients and plasma HDL-C, Glu, and SBP levels in the control subjects. The apoA1 variant-associated lipids and SBP variation is BMI dependent in both groups.
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Apolipoproteína A-I , Diabetes Gestacional , Feminino , Humanos , Gravidez , Apolipoproteína A-I/genética , HDL-Colesterol , Frequência do Gene , Genótipo , Lipídeos , Obesidade , Polimorfismo de Nucleotídeo Único , Regiões Promotoras GenéticasRESUMO
The titanium-stabilized austenitic stainless steel Fe-15Cr-15Ni, which shows enhanced resistance to irradiation swelling compared with more traditional 316Ti, has been selected as a core material for fast reactors. Data on the evolution of irradiation swelling in 15-15Ti steels at very high doses, which cannot be easily achieved by neutron irradiation, are still lacking. In this paper, the swelling behavior of the titanium-modified austenitic stainless steel 15-15Ti was investigated by pre-implantation of He at room temperature followed by Ni-ion irradiation at 580 °C to peak doses of 120, 240 and 400 dpa. Relatively small cavities were observed in the zone of helium implantation, while large cavities appeared in the region near the damage peak. A correction formula for the dpa curve was proposed and applied to samples with large swelling. It was found that the steady-state swelling rate of 15-15Ti remains at ~1%/dpa even at high doses. By comparing the swelling data of the helium-implanted and helium-free regions at same doses, 70 dpa and 122 dpa, the suppression of swelling by excessive helium can be deduced at such doses.
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PURPOSE: To determine the relationship between serum total testosterone (TT) levels and oxidative stress indices in patients with polycystic ovary syndrome (PCOS), and to investigate the effect of oxidative stress on androgen synthesis and its mechanism in rat ovarian theca-interstitial (T-I) cells. METHODS: Clinical, hormonal, metabolic, and oxidative stress parameters were analyzed in a cross-sectional case-control study including 626 patients with PCOS and 296 controls. The effects of oxidized low-density lipoprotein (ox-LDL) and oxidized high-density lipoprotein (ox-HDL) on cell proliferation, TT secretion, and expression of key enzymes involved in testosterone synthesis were evaluated in T-I cells. RESULTS: Serum TT levels were elevated with an increase in ox-LDL levels, whereas glutathione concentrations were lower in the high-TT subgroup than in the low-TT subgroup. The average ovarian volume and ox-LDL and malondialdehyde levels were significant predictors of TT levels in the multivariate regression models. In a rat ovarian T-I cell model, lipoprotein and oxidized lipoprotein treatments stimulated proliferation and promoted testosterone secretion. The mRNA and protein levels of 17α-hydroxylase were significantly higher in oxidized lipoprotein-treated cells than those in lipoprotein-treated cells. The mRNA levels of cholesterol side chain cleavage enzyme and steroidogenic acute regulatory protein were also significantly higher in ox-HDL-treated cells than in HDL-treated cells. CONCLUSIONS: Oxidative stress can promote androgen production by up-regulating the expression of testosterone synthesis-related enzymes in vitro and may be an essential factor in elevating serum TT levels in patients with PCOS.
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Hiperandrogenismo , Lipoproteínas LDL , Estresse Oxidativo , Síndrome do Ovário Policístico , Testosterona , Síndrome do Ovário Policístico/metabolismo , Feminino , Animais , Ratos , Testosterona/sangue , Lipoproteínas LDL/sangue , Lipoproteínas LDL/metabolismo , Hiperandrogenismo/metabolismo , Adulto , Humanos , Estudos de Casos e Controles , Estudos Transversais , Ovário/metabolismo , Ratos Sprague-Dawley , Adulto Jovem , Células Tecais/metabolismo , Proliferação de Células , Androgênios/sangue , Esteroide 17-alfa-Hidroxilase/metabolismo , Esteroide 17-alfa-Hidroxilase/genética , Células CultivadasRESUMO
Oxidative stress and metabolic disorders are involved in the pathogenesis of polycystic ovary syndrome (PCOS). Heme oxygenase 2 (HMOX2) plays a critical role in preserving heme metabolism as well as in modulating glycolipid metabolism, oxidative stress, and inflammation. This study examined the correlation between HMOX2 G554A (rs1051308) and A-42G (rs2270363) genetic variants with the risk of PCOS and assessed the effects of these genotypes on clinical, hormonal, metabolic, and oxidative stress indices using a case-control design that included 1014 patients with PCOS and 806 control participants. We found that the allelic and genotypic frequencies of the HMOX2 G554A and A-42G polymorphisms were comparable between the PCOS and control groups in Chinese women (P > 0.05). Nevertheless, it was discovered that patients with the AA or AG genotype of A-42G polymorphism had notably elevated levels of estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), LH/FSH ratio, high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), apolipoprotein (apo)B, and/or apoB/apoA1 ratio than those with the GG genotypes (P < 0.05). Patients with the GG or AG genotype of G554A polymorphism had elevated serum levels of LH, FSH, E2, LH/FSH ratio, TC, HDL-C, LDL-C, apoB, and/or apoB/apoA1 ratio and lower 2-h glucose concentration compared with those with the AA genotype (P < 0.05). Our findings indicate a potential association between the genetic variants and endocrine abnormalities in the reproductive system and metabolic irregularities in glycolipid levels in patients, thus suggesting their potential role in the pathogenesis of PCOS.
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Integration of methanogenic archaea with photocatalysts presents a sustainable solution for solar-driven methanogenesis. However, maximizing CH4 conversion efficiency remains challenging due to the intrinsic energy conservation and strictly restricted substrates of methanogenic archaea. Here, we report a solar-driven biotic-abiotic hybrid (biohybrid) system by incorporating cadmium sulfide (CdS) nanoparticles with a rationally designed methanogenic archaeon Methanosarcina acetivorans C2A, in which the glucose synergist protein and glucose kinase, an energy-efficient route for glucose transport and phosphorylation from Zymomonas mobilis, were implemented to facilitate nonnative substrate glucose for methanogenesis. We demonstrate that the photo-excited electrons facilitate membrane-bound electron transport chain, thereby augmenting the Na+ and H+ ion gradients across membrane to enhance adenosine triphosphate (ATP) synthesis. Additionally, this biohybrid system promotes the metabolism of pyruvate to acetyl coenzyme A (AcCoA) and inhibits the flow of AcCoA to the tricarboxylic acid (TCA) cycle, resulting in a 1.26-fold augmentation in CH4 production from glucose-derived carbon. Our results provide a unique strategy for enhancing methanogenesis through rational biohybrid design and reprogramming, which gives a promising avenue for sustainably manufacturing value-added chemicals.
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Trifosfato de Adenosina , Metano , Metano/metabolismo , Transporte de Elétrons , Trifosfato de Adenosina/metabolismo , Metabolismo Energético , Transporte Biológico , Methanosarcina/metabolismoRESUMO
Exploring new near-room-temperature thermoelectric materials is significant for replacing current high-cost Bi2Te3. This study highlights the potential of Ag2Se for wearable thermoelectric electronics, addressing the trade-off between performance and flexibility. A record-high ZT of 1.27 at 363 K is achieved in Ag2Se-based thin films with 3.2 at.% Te doping on Se sites, realized by a new concept of doping-induced orientation engineering. We reveal that Te-doping enhances film uniformity and (00l)-orientation and in turn carrier mobility by reducing the (00l) formation energy, confirmed by solid computational and experimental evidence. The doping simultaneously widens the bandgap, resulting in improved Seebeck coefficients and high power factors, and introduces TeSe point defects to effectively reduce the lattice thermal conductivity. A protective organic-polymer-based composite layer enhances film flexibility, and a rationally designed flexible thermoelectric device achieves an output power density of 1.5 mW cm-2 for wearable power generation under a 20 K temperature difference.
RESUMO
Osteoporosis is a systemic bone disease characterized by low bone mineral density and bone microstructure damage, resulting in increased bone fragility and fracture risk. The present study aimed to identify key genes and functionally enriched pathways in osteoporotic patients. Weighted Gene Co-expression Network Analysis (WGCNA) was applied to microarray datasets of blood samples of osteoporotic patients from the Sao Paulo Ageing & Health [SPAH] study (26 osteoporotic samples and 31 normal samples) to construct co-expression networks and identify hub gene. The results showed that HDGF, AP2M1, DNAJC6, TMEM183B, MFSD2B, IGKV1-5, IGKV1-8, IGKV3-7, IGKV3D-11, and IGKV1D-42 are genes which were associated with the disease status of osteoporosis. Differentially expressed genes are enriched in proteasomal protein catabolic process, ubiquitin ligase complex, and ubiquitin-like protein transferase activity. Functional enrichment analysis demonstrated that genes in the tan module were enriched in immune-related functions, indicating that the immune system plays a critical role in osteoporosis. Validation assay demonstrated that the HDGF, AP2M1, TMEM183B, and MFSD2B levels were decreased in osteoporosis samples compared with healthy controls, while the levels of IGKV1-5, IGKV1-8, and IGKV1D-42 were increased in osteoporosis samples compared with healthy controls. In conclusion, our data identified and validated the association of HDGF, AP2M1, TMEM183B, MFSD2B, IGKV1-5, IGKV1-8, and IGKV1D-42 with osteoporosis in elderly women. These results suggest that these transcripts have potential clinical significance and may help to explain the molecular mechanisms and biological functions of osteoporosis.
Assuntos
Perfilação da Expressão Gênica , Osteoporose , Humanos , Feminino , Idoso , Brasil , Perfilação da Expressão Gênica/métodos , Osteoporose/genética , Expressão GênicaRESUMO
Antimony triselenide (Sb2 Se3 ) has possessed excellent optoelectronic properties and has gained interest as a light-harvesting material for photovoltaic technology over the past several years. However, the severe interfacial and bulk recombination obviously contribute to significant carrier transport loss thus leading to the deterioration of power conversion efficiency (PCE). In this work, buried interface and heterojunction engineering are synergistically employed to regulate the film growth kinetic and optimize the band alignment. Through this approach, the orientation of the precursor films is successfully controlled, promoting the preferred orientational growth of the (hk1) of the Sb2 Se3 films. Besides, interfacial trap-assisted nonradiative recombination loss and heterojunction band alignment are successfully minimized and optimized. As a result, the champion device presents a PCE of 9.24% with short-circuit density (JSC ) and fill factor (FF) of 29.47 mA cm-2 and 63.65%, respectively, representing the highest efficiency in sputtered-derived Sb2 Se3 solar cells. This work provides an insightful prescription for fabricating high-quality Sb2 Se3 thin film and enhancing the performance of Sb2 Se3 solar cells.