Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.661
Filtrar
1.
Acta Pharm Sin B ; 14(4): 1624-1643, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38572092

RESUMO

HMGA2, a pivotal transcription factor, functions as a versatile regulator implicated in the progression of diverse aggressive malignancies. In this study, mass spectrometry was employed to identify ubiquitin-specific proteases that potentially interact with HMGA2, and USP48 was identified as a deubiquitinating enzyme of HMGA2. The enforced expression of USP48 significantly increased HMGA2 protein levels by inhibiting its degradation, while the deprivation of USP48 promoted HMGA2 degradation, thereby suppressing tumor invasion and metastasis. We discovered that USP48 undergoes SUMOylation at lysine 258, which enhances its binding affinity to HMGA2. Through subsequent phenotypic screening of small molecules, we identified DUB-IN-2 as a remarkably potent pharmacological inhibitor of USP48. Interestingly, the small-molecule inhibitor targeting USP48 induces destabilization of HMGA2. Clinically, upregulation of USP48 or HMGA2 in cancerous tissues is indicative of poor prognosis for patients with colorectal cancer (CRC). Collectively, our study not only elucidates the regulatory mechanism of DUBs involved in HMGA2 stability and validates USP48 as a potential therapeutic target for CRC, but also identifies DUB-IN-2 as a potent inhibitor of USP48 and a promising candidate for CRC treatment.

2.
Sci Rep ; 14(1): 8132, 2024 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-38584153

RESUMO

To figure out how does SARS-CoV-2 affect sperm parameters and what influencing factors affect the recovery of sperm quality after infection? We conducted a prospective cohort study and initially included 122 men with SARS-CoV-2 infection. The longest time to track semen quality after infection is 112 days and 58 eligible patients were included in our study eventually. We subsequently exploited a linear mixed-effects model to statistically analyze their semen parameters at different time points before and after SARS-CoV-2 infection. Semen parameters were significantly reduced after SARS-CoV-2 infection, including total sperm count (211 [147; 347] to 167 [65.0; 258], P < 0.001), sperm concentration (69.0 [38.8; 97.0] to 51.0 [25.5; 71.5], P < 0.001), total sperm motility (57.5 [52.3; 65.0] to 51.0 [38.5; 56.8], P < 0.001), progressive motility (50.0 [46.2; 58.0] to 45.0 [31.5; 52.8], P < 0.001). The parameters displayed the greatest diminution within 30 days after SARS-CoV-2 infection, gradually recovered thereafter, and exhibited no significant difference after 90 days compared with prior to COVID-19 infection. In addition, the patients in the group with a low-grade fever showed a declining tendency in semen parameters, but not to a significant degree, whereas those men with a moderate or high fever produced a significant drop in the same parameters. Semen parameters were significantly reduced after SARS-CoV-2 infection, and fever severity during SARS-CoV-2 infection may constitute the main influencing factor in reducing semen parameters in patients after recovery, but the effect is reversible and the semen parameters gradually return to normal with the realization of a new spermatogenic cycle.


Assuntos
COVID-19 , Infertilidade Masculina , Humanos , Masculino , Análise do Sêmen , Sêmen , Estudos Prospectivos , Motilidade dos Espermatozoides , SARS-CoV-2 , Espermatozoides , Contagem de Espermatozoides
3.
Nano Lett ; 24(15): 4610-4617, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38564191

RESUMO

The intricate protonation process in carbon dioxide reduction usually makes the product unpredictable. Thus, it is significant to control the reactive intermediates to manipulate the reaction steps. Here, we propose that the synergistic La-Ti active sites in the N-La2Ti2O7 nanosheets enable the highly selective carbon dioxide photoreduction into methane. In the photoreduction of CO2 over N-La2Ti2O7 nanosheets, in situ Fourier transform infrared spectra are utilized to monitor the *CH3O intermediate, pivotal for methane production, whereas such monitoring is not conducted for La2Ti2O7 nanosheets. Also, theoretical calculations testify to the increased charge densities on the Ti and La atoms and the regulated formation energy barrier of *CO and *CH3O intermediates by the constructed synergistic active sites. Accordingly, the methane formation rate of 7.97 µL h-1 exhibited by the N-La2Ti2O7 nanosheets, along with an electron selectivity of 96.6%, exceeds that of most previously reported catalysts under similar conditions.

5.
Biomed Environ Sci ; 37(2): 178-186, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38582980

RESUMO

Objective: This study aimed to compare the current Essen rabies post-exposure immunization schedule (0-3-7-14-28) in China and the simple 4-dose schedule (0-3-7-14) newly recommended by the World Health Organization in terms of their safety, efficacy, and protection. Methods: Mice were vaccinated according to different immunization schedules, and blood was collected for detection of rabies virus neutralizing antibodies (RVNAs) on days 14, 21, 28, 35, and 120 after the first immunization. Additionally, different groups of mice were injected with lethal doses of the CVS-11 virus on day 0, subjected to different rabies immunization schedules, and assessed for morbidity and death status. In a clinical trial, 185 rabies-exposed individuals were selected for post-exposure vaccination according to the Essen schedule, and blood was collected for RVNAs detection on days 28 and 42 after the first immunization. Results: A statistically significant difference in RVNAs between mice in the Essen and 0-3-7-14 schedule groups was observed on the 35th day ( P < 0.05). The groups 0-3-7-14, 0-3-7-21, and 0-3-7-28 showed no statistically significant difference ( P > 0.05) in RVNAs levels at any time point. The post-exposure immune protective test showed that the survival rate of mice in the control group was 20%, whereas that in the immunization groups was 40%. In the clinical trial, the RVNAs positive conversion rates on days 28 (14 days after 4 doses) and 42 (14 days after 5 doses) were both 100%, and no significant difference in RVNAs levels was observed ( P > 0.05). Conclusion: The simple 4-dose schedule can produce sufficient RVNAs levels, with no significant effect of a delayed fourth vaccine dose (14-28 d) on the immunization potential.


Assuntos
Vacina Antirrábica , Vírus da Raiva , Raiva , Animais , Camundongos , Raiva/prevenção & controle , Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinação , China , Profilaxia Pós-Exposição
6.
Sci Total Environ ; 927: 172368, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38614346

RESUMO

BACKGROUND: Disinfection byproducts (DBPs) have been shown to impair thyroid function in experimental models. However, epidemiological evidence is scarce. METHODS: This study included 1190 women undergoing assisted reproductive technology (ART) treatment from the Tongji Reproductive and Environmental (TREE) cohort from December 2018 to August 2021. Serum thyrotropin (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) were measured as indicators of thyroid function. FT4/FT3 and TSH/FT4 ratios were calculated as markers of thyroid hormone homeostasis. Dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA), the two most abundant HAAs, in urine were detected to assess individual DBP exposures. RESULTS: After adjusting for relevant covariates, positive associations were observed between urinary TCAA concentrations and serum TSH and TSH/FT4 levels (e.g., percent change = 5.82 %, 95 % CI: 0.70 %, 11.21 % for TSH), whereas inverse associations were found for serum FT3 and FT4 (e.g., percent change = -1.29 %, 95 % CI: -2.49 %, -0.07 % for FT3). There also was a negative association between urinary DCAA concentration and serum FT4/FT3 (percent change = -2.49 %, 95 % CI: -4.71 %, -0.23 %). These associations were further confirmed in the restricted cubic spline and generalized additive models with linear or U-shaped dose-response relationships. CONCLUSION: Urinary HAAs were associated with altered thyroid hormone homeostasis among women undergoing ART treatment.


Assuntos
Glândula Tireoide , Humanos , Feminino , Adulto , Tiroxina/sangue , Tri-Iodotironina/sangue , Tireotropina/sangue , Hormônios Tireóideos/sangue , Testes de Função Tireóidea , Desinfetantes , Acetatos , China
7.
Sci Total Environ ; 927: 172156, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38588742

RESUMO

The variability and intrinsic mechanisms of oxidative stress induced by microplastics at different trophic levels in freshwater food chains are not well understood. To comprehensively assess the oxidative stress induced by polystyrene microplastics (PS-MPs) in freshwater food chains, the present study first quantified the oxidative stress induced by PS-MPs in organisms at different trophic levels using factorial experimental design and molecular dynamics methods. Then focuses on analyzing the variability of these responses across different trophic levels using mathematical statistical analysis. Notably, higher trophic level organisms exhibit diminished responses under PS-MPs exposure. Furthermore, the coexistence of multiple additives was found to mask these responses, with antioxidant plastic additives significantly influencing oxidative stress responses. Mechanism analysis using computational chemistry simulation determines that protein structure and amino acid characteristics are key factors driving PS-MPs induced oxidative stress variation in freshwater organisms at different nutrient levels. Increased hydrophobic additives induce protein helicalization and amino acid residue aggregation. This study systematically reveals the variability of biological oxidative stress response under different nutrient levels, emphasizing the pivotal role of chemical additives. Overall, this study offers crucial insights into PS-MPs' impact on oxidative stress responses in freshwater ecosystems, informing future environmental risk assessment.


Assuntos
Cadeia Alimentar , Água Doce , Microplásticos , Estresse Oxidativo , Poluentes Químicos da Água , Estresse Oxidativo/efeitos dos fármacos , Microplásticos/toxicidade , Poluentes Químicos da Água/toxicidade , Água Doce/química , Animais , Poliestirenos/toxicidade , Organismos Aquáticos/efeitos dos fármacos
8.
Mol Biol Rep ; 51(1): 520, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38625436

RESUMO

BACKGROUND: Mutations in human ether-à-go-go-related gene (hERG) potassium channels are closely associated with long QT syndrome (LQTS). Previous studies have demonstrated that macrolide antibiotics increase the risk of cardiovascular diseases. To date, the mechanisms underlying acquired LQTS remain elusive. METHODS: A novel hERG mutation I1025N was identified in an azithromycin-treated patient with acquired long QT syndrome via Sanger sequencing. The mutant I1025N plasmid was transfected into HEK-293 cells, which were subsequently incubated with azithromycin. The effect of azithromycin and mutant I1025N on the hERG channel was evaluated via western blot, immunofluorescence, and electrophysiology techniques. RESULTS: The protein expression of the mature hERG protein was down-regulated, whereas that of the immature hERG protein was up-regulated in mutant I1025N HEK-293 cells. Azithromycin administration resulted in a negative effect on the maturation of the hERG protein. Additionally, the I1025N mutation exerted an inhibitory effect on hERG channel current. Moreover, azithromycin inhibited hERG channel current in a concentration-dependent manner. The I1025N mutation and azithromycin synergistically decreased hERG channel expression and hERG current. However, the I1025N mutation and azithromycin did not alter channel gating dynamics. CONCLUSIONS: These findings suggest that hERG gene mutations might be involved in the genetic susceptibility mechanism underlying acquired LQTS induced by azithromycin.


Assuntos
Azitromicina , Síndrome do QT Longo , Humanos , Azitromicina/efeitos adversos , Células HEK293 , Antibacterianos/efeitos adversos , Síndrome do QT Longo/induzido quimicamente , Síndrome do QT Longo/genética , Mutação
9.
Materials (Basel) ; 17(7)2024 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-38611996

RESUMO

Due to its inherent high hardness, strength, and plasticity, tantalum-tungsten (Ta-W) alloy poses a considerable challenge in machining, resulting in pronounced tool wear, diminished tool lifespan, and suboptimal surface quality. This study undertook experiments utilizing uncoated carbide tools, TiAlN-coated carbide tools, and AlTiN-coated carbide tools for machining Ta-2.5W alloy. The investigation delved into the intricacies of surface temperature, tool longevity, and the distinctive wear characteristics under varying coating materials and cutting parameters. Concurrently, a comprehensive exploration of the wear mechanisms affecting the tools was conducted. Among the observed wear modes, flank wear emerged as the predominant issue for turning tools. Across all three tool types, adhesive wear and diffusion wear were identified as the principal wear mechanisms, with the TiAlN-coated tools displaying a reduced level of wear compared to their AlTiN-coated counterparts. The experimental findings conclusively revealed that TiAlN-coated carbide tools exhibited an extended tool lifespan in comparison to uncoated carbide tools and AlTiN-coated carbide tools, signifying superior cutting performance.

10.
Plants (Basel) ; 13(6)2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38592823

RESUMO

The importance of rootstock in citrus production lies in its crucial role in determining tree growth, environmental stress tolerance, and fruit quality. Citrus junos Siebold ex Tanaka cv. Shuzhen No. 1, a recently developed rootstock, demonstrates excellent graft compatibility and abiotic stress tolerance. The objective of this study was to assess ten hybrid citrus cultivars grafted onto two C. junos rootstock selections, with the aim of determining the potential for industrial utilization of the new citrus rootstock. All graft junctions are mature and well established. Vigorous growth characterized all ten citrus cultivars on Shuzhen No. 1, with the largest tree's height reaching 280.33 cm (Wogan scion) and the widest scion's diameter being 67.52 cm (Chunjian scion). However, the scion-to-rootstock diameter ratio was the lowest at 0.62 (Chunxiang scion). C. junos rootstock selections significantly affected fruit weight (five of ten scions) and fruit color (seven of ten scions) but had negligible impact on peel thickness (nine of ten scions). Furthermore, rootstock type had a significant influence on fruit quality. In conclusion, our findings indicate strong graft compatibility between all scions and C. junos rootstocks, which can impact overall size and fruit quality. Based on these results, Shuzhen No. 1 is recommended as a valuable citrus rootstock.

11.
ACS Appl Mater Interfaces ; 16(15): 19751-19763, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38581368

RESUMO

Diamond is widely acknowledged as the hardest naturally occurring material. Nevertheless, when exposed to friction against ferrous metals, it is prone to graphitization or amorphization, which limits the utilization of its extremely high hardness and wear resistance. These issues have persisted for decades without an effective solution. Here, we report that a covalently bonded heterostructure with mixed-dimensional carbons as a high-performance solid lubricant could effectively reduce diamond surface friction and mechanochemical wear with excellent load capacity and durability. When subjected to dry friction and heavy loads (20-150 N), the heterostructure exhibited a notable improvement over pristine diamond with reduced friction coefficients and relative wear rates by 22-45 and 67-91%, respectively. Especially under a 20 N load, the relative wear rate was an order of magnitude lower than that of pristine diamond. Additionally, experiments and molecular dynamics simulations revealed that the heterostructure integrated the outstanding properties of diamond (three-dimensional (3D)), nanographite (3D), and graphene (two-dimensional (2D)), resulting in improved lubrication and antiwear performance that could not be achieved by the individual carbon materials. The findings in this work will be beneficial to overcome the ferrous metal forbidden zone of diamond and are expected to expand the applications of engineered diamond surfaces and graphite/graphene in tribology, mechanics, and electronic fields.

12.
Sci Total Environ ; 928: 172411, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38608898

RESUMO

Exposure to diisodecyl phthalate (DIDP) during early pregnancy may be a risk factor for depressive behavior in offspring. While ozone (O3) exposure also raises the probability of depressive behavior during the preceding DIDP-induced process. In the present study, we investigated the effects of prenatal exposure to DIDP and O3 on the development of depressive-like behavior in offspring mice. The study found that prenatal exposure to both DIDP and O3 significantly increased depressive-like behavior in the offspring mice compared to either DIDP or O3 alone. Prenatal exposure to DIDP and O3 obviously increased the levels of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and cortisol, and decreased the levels of brain-derived neurotrophic factor (BDNF), 5-hydroxytryptamine (5-HT), dopamine (DA) and norepinephrine (NE) in the brain tissues of offspring mice. Transcriptome analysis further revealed significant alterations in genes related to oxidative stress and TWIST1 (a helix-loop-helix transcription factor) in response to the combined exposure to DIDP and O3. HPA axis activation, dysregulation of neurodevelopmental factors, oxidative stress and TWIST1 involvement, collectively contributed to the development of depression-like behaviors in offspring mice following prenatal exposure to DIDP and O3. Moreover, the study also verified the potential role of oxidative stress using vitamin E as an antioxidant. The findings provide valuable evidence for the relationship between co-exposure to DIDP and O3 and depression, highlighting the importance of considering the combined effects of multiple environmental pollutants in assessing their impact on mental health outcomes.

13.
Artigo em Inglês | MEDLINE | ID: mdl-38656850

RESUMO

Text content analysis for depression detection using machine learning techniques has become a prominent area of research. However, previous studies focused mainly on analyzing the textual content, neglecting the fundamental factors driving text generation. Consequently, existing models face the challenge of poor generalization to out-of-domain data as they struggle to capture the crucial features of depression. To address this, we propose a novel computational perspective of "stimulus-response patterns" that brings us closer to the essence of clinical diagnosis of depression. Adopting this computational perspective allows us to conceptually unify diverse datasets and generalize this perspective to common datasets in the field. We introduce the Stimulus-Response Patterns-aware Network (SRP-Net) as an exemplary approach within this computational perspective. To assess the performance of the SRP-Net, we constructed a multi-stimulus dataset and conducted experimental evaluations, demonstrating its exceptional cross-stimulus generalizability. Furthermore, we demonstrated the promising performance of SPR-Net in real medical scenarios and conducted an interpretability analysis of the stimulus-response patterns. Our research investigates the critical role of stimulus-response patterns in enhancing the generalizability of text-based depression detection models, which can potentially facilitate data-driven depression detection to approach the diagnostic accuracy of psychiatrists.

14.
World J Clin Cases ; 12(10): 1793-1798, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38660069

RESUMO

BACKGROUND: Whether hyperbaric oxygen therapy (HBOT) can cause paradoxical herniation is still unclear. CASE SUMMARY: A 65-year-old patient who was comatose due to brain trauma underwent decompressive craniotomy and gradually regained consciousness after surgery. HBOT was administered 22 d after surgery due to speech impairment. Paradoxical herniation appeared on the second day after treatment, and the patient's condition worsened after receiving mannitol treatment at the rehabilitation hospital. After timely skull repair, the paradoxical herniation was resolved, and the patient regained consciousness and had a good recovery as observed at the follow-up visit. CONCLUSION: Paradoxical herniation is rare and may be caused by HBOT. However, the underlying mechanism is unknown, and the understanding of this phenomenon is insufficient. The use of mannitol may worsen this condition. Timely skull repair can treat paradoxical herniation and prevent serious complications.

15.
World J Clin Cases ; 12(10): 1799-1803, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38660075

RESUMO

BACKGROUND: The precise mechanism by which severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) impacts the central nervous system remains unclear, with manifestations spanning from mild symptoms (e.g., olfactory and gustatory deficits, hallucinations, and headache) to severe complications (e.g., stroke, seizures, encephalitis, and neurally demyelinating lesions). The occurrence of single-pass subdural effusion, as described below, is extremely rare. CASE SUMMARY: A 56-year-old male patient presented with left-sided limb weakness and slurred speech as predominant clinical symptoms. Through comprehensive imaging and diagnostic assessments, he was diagnosed with cerebral infarction complicated by hemorrhagic transformation affecting the right frontal, temporal, and parietal regions. In addition, an intracranial infection with SARS-CoV-2 was identified during the rehabilitation process; consequently, an idiopathic subdural effusion developed. Remarkably, the subdural effusion underwent absorption within 6 d, with no recurrence observed during the 3-month follow-up. CONCLUSION: Subdural effusion is a potentially rare intracranial complication associated with SARS-CoV-2 infection.

16.
J Am Chem Soc ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38626786

RESUMO

Photocatalytic conversion of methane (CH4) to ethane (C2H6) has attracted extensive attention from academia and industry. Typically, the traditional oxidative coupling of CH4 (OCM) reaches a high C2H6 productivity, yet the inevitable overoxidation limits the target product selectivity. Although the traditional nonoxidative coupling of CH4 (NOCM) can improve the product selectivity, it still encounters unsatisfied activity, arising from being thermodynamically unfavorable. To break the activity-selectivity trade-off, we propose a conceptually new mechanism of H2O2-triggered CH4 coupling, where the H2O2-derived ·OH radicals are rapidly consumed for activating CH4 into ·CH3 radicals exothermically, which bypasses the endothermic steps of the direct CH4 activation by photoholes and the interaction between ·CH3 and ·OH radicals, affirmed by in situ characterization techniques, femtosecond transient absorption spectroscopy, and density-functional theory calculation. By this pathway, the designed Au-WO3 nanosheets achieve unprecedented C2H6 productivity of 76.3 mol molAu-1 h-1 with 95.2% selectivity, and TON of 1542.7 (TOF = 77.1 h-1) in a self-designed flow reactor, outperforming previously reported photocatalysts regardless of OCM and NOCM pathways. Also, under outdoor natural sunlight irradiation, the Au-WO3 nanosheets exhibit similar activity and selectivity toward C2H6 production, showing the possibility for practical applications. Interestingly, this strategy can be applied to other various photocatalysts (Au-WO3, Au-TiO2, Au-CeO2, Pd-WO3, and Ag-WO3), showing a certain universality. It is expected that the proposed mechanism adds another layer to our understanding of CH4-to-C2H6 conversion.

17.
Nat Commun ; 15(1): 3399, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649376

RESUMO

The van der Waals antiferromagnetic topological insulator MnBi2Te4 represents a promising platform for exploring the layer-dependent magnetism and topological states of matter. Recently observed discrepancies between magnetic and transport properties have aroused controversies concerning the topological nature of MnBi2Te4 in the ground state. In this article, we demonstrate that fabrication can induce mismatched even-odd layer dependent magnetotransport in few-layer MnBi2Te4. We perform a comprehensive study of the magnetotransport properties in 6- and 7-septuple-layer MnBi2Te4, and reveal that both even- and odd-number-layer device can show zero Hall plateau phenomena in zero magnetic field. Importantly, a statistical survey of the optical contrast in more than 200 MnBi2Te4 flakes reveals that the zero Hall plateau in odd-number-layer devices arises from the reduction of the effective thickness during the fabrication, a factor that was rarely noticed in previous studies of 2D materials. Our finding not only provides an explanation to the controversies regarding the discrepancy of the even-odd layer dependent magnetotransport in MnBi2Te4, but also highlights the critical issues concerning the fabrication and characterization of 2D material devices.

18.
RSC Adv ; 14(16): 11217-11231, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38590351

RESUMO

The present investigation delves into the adverse environmental impact of atmospheric pollutant gases, specifically nitrogen dioxide (NO2) and sulfur dioxide (SO2), which necessitates the identification and implementation of effective control measures. The central objective of this study is to explore the eradication of these pollutants through the utilization of aluminum Al13 and Al15 metal clusters, distinguished by their unique properties. The comprehensive evaluation of gas/cluster interactions is undertaken employing density functional theory (DFT). Geometric optimization calculations for all structures are executed using the ωB97XD functional and the Def2-svp basis set. To probe various interaction modalities, gas molecule distribution around the metal clusters is sampled using the bee colony algorithm. Frequency calculations employing identical model chemistry validate the precision of the optimization calculations. The quantum theory of atoms in molecules (QTAIM) and natural bond orbital (NBO) methodologies are applied for the analysis of intermolecular interactions. This research establishes the robust formation of van der Waals attractions between the investigated gas molecules, affirming aluminum metal clusters as viable candidates for the removal and control of these gases.

19.
BMC Genomics ; 25(1): 280, 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38493091

RESUMO

BACKGROUND: Atrial fibrillation (AF) is a prevalent arrhythmic condition resulting in increased stroke risk and is associated with high mortality. Electrolyte imbalance can increase the risk of AF, where the relationship between AF and serum electrolytes remains unclear. METHODS: A total of 15,792 individuals were included in the observational study, with incident AF ascertainment in the Atherosclerosis Risk in Communities (ARIC) study. The Cox regression models were applied to calculate the hazard ratio (HR) and 95% confidence interval (CI) for AF based on different serum electrolyte levels. Mendelian randomization (MR) analyses were performed to examine the causal association. RESULTS: In observational study, after a median 19.7 years of follow-up, a total of 2551 developed AF. After full adjustment, participants with serum potassium below the 5th percentile had a higher risk of AF relative to participants in the middle quintile. Serum magnesium was also inversely associated with the risk of AF. An increased incidence of AF was identified in individuals with higher serum phosphate percentiles. Serum calcium levels were not related to AF risk. Moreover, MR analysis indicated that genetically predicted serum electrolyte levels were not causally associated with AF risk. The odds ratio for AF were 0.999 for potassium, 1.044 for magnesium, 0.728 for phosphate, and 0.979 for calcium, respectively. CONCLUSIONS: Serum electrolyte disorders such as hypokalemia, hypomagnesemia and hyperphosphatemia were associated with an increased risk of AF and may also serve to be prognostic factors. However, the present study did not support serum electrolytes as causal mediators for AF development.


Assuntos
Fibrilação Atrial , Humanos , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/genética , Fatores de Risco , Magnésio , Análise da Randomização Mendeliana , Cálcio , Potássio , Fosfatos , Eletrólitos , Estudo de Associação Genômica Ampla/métodos
20.
J Nanobiotechnology ; 22(1): 117, 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38493145

RESUMO

Reactive oxygen species (ROS) has emerged as potent therapeutic agents for biofilm-associated bacterial infections. Chemodynamic therapy (CDT), involving the generation of high-energy ROS, displays great potential in the therapy of bacterial infections. However, challenges such as insufficient hydrogen peroxide (H2O2) and over-expressed glutathione (GSH) levels within the microenvironment of bacterial biofilms severely limit the antibacterial efficacy of CDT. Herein, we have developed a multifunctional nanoplatform (CuS@CaO2@Dex) by integrating copper sulfide (CuS) and calcium peroxide (CaO2) into dextran (Dex)-coated nanoparticles. This innovative platform enhanced ROS generation for highly efficient biofilm elimination by simultaneously supplying H2O2 and depleting GSH. The Dex-coating facilitated the penetrability of CuS@CaO2@Dex into biofilms, while CaO2 generated a substantial amount of H2O2 in the acidic biofilm microenvironment. CuS, through a Fenton-like reaction, catalyzed the conversion of self-supplied H2O2 into hydroxyl radicals (•OH) and consumed the overexpressed GSH. Additionally, the incorporation of near-infrared II (NIR II) laser irradiation enhanced the photothermal properties of CuS, improving the catalytic efficiency of the Fenton-like reaction for enhanced antibacterial effects. In vivo experiments have demonstrated that CuS@CaO2@Dex exhibited remarkable antibacterial and antibiofilm efficacy, exceptional wound healing capabilities, and notable biosafety. In summary, the Dex-coated nanoplatform proposed in this study, with its self-sterilization capability through ROS, holds significant potential for future biomedical applications.


Assuntos
Infecções Bacterianas , Staphylococcus aureus Resistente à Meticilina , Neoplasias , Humanos , Peróxido de Hidrogênio/farmacologia , Espécies Reativas de Oxigênio , Antibacterianos/farmacologia , Biofilmes , Glutationa , Linhagem Celular Tumoral , Microambiente Tumoral
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...