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1.
J Environ Sci (China) ; 150: 556-570, 2025 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-39306429

RESUMEN

Elucidating the mutual effects between the different volatile organic compounds (VOCs) is crucial for comprehending the formation mechanism of atmospheric secondary organic aerosols (SOA). Here, the mixed VOCs experiments of isoprene and Δ3-carene/ß-caryophyllene were carried out in the presence of O3 using an indoor smog chamber. The suppression effect of isoprene was recognized by the scanning mobility particle sizer spectrometer, online vacuum ultraviolet free electron laser (VUV-FEL) photoionization aerosol mass spectrometry, and quantum chemical calculations. The results indicate that the suppression effect of isoprene on the ozonolysis of Δ3-carene and ß-caryophyllene shows fluctuating and monotonous trends, respectively. The carbon content of the precursor could be the main factor for regulating the strength of the suppression effect. Plausible structures and formation mechanisms of several new products generated from the single VOC precursor and VOC-cross-reaction are proposed, which enrich the category of VOC oxidation products. Meanwhile, a new dimerization mechanism of the RO2 + R'O2 reaction is suggested, which offers an intriguing perspective on the gas phase formation process of particle phase accretion products. The present findings provide valuable insights into clarifying the pivotal roles played by isoprene in the interplay between different VOCs and understanding of SOA formation mechanisms of VOC mixtures, especially nearby the emission origins.


Asunto(s)
Aerosoles , Contaminantes Atmosféricos , Butadienos , Hemiterpenos , Ozono , Sesquiterpenos Policíclicos , Compuestos Orgánicos Volátiles , Butadienos/química , Hemiterpenos/química , Ozono/química , Sesquiterpenos Policíclicos/química , Contaminantes Atmosféricos/química , Compuestos Orgánicos Volátiles/química , Modelos Químicos , Dimerización
2.
World J Gastrointest Surg ; 16(9): 3057-3064, 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39351559

RESUMEN

BACKGROUND: Gastric submucosal arterial dilation resulting from splenic artery occlusion represents an exceedingly rare etiology of acute upper gastrointestinal bleeding (UGIB). Although endoscopy is a widely utilized diagnostic and therapeutic modality for gastrointestinal bleeding, it has limitations in detecting arterial abnormalities. CASE SUMMARY: This report presents a rare case of massive UGIB in a 57-year-old male with a tortuous left inferior phrenic artery accompanied by splenic artery occlusion. "Gastric varices" was identified during the patient's endoscopy one year before hemorrhage. Despite initial hemostasis by endoscopic clipping, the patient experienced massive rebleeding after one month, requiring intervention with transcatheter arterial embolization (TAE) to achieve hemostasis. CONCLUSION: This is the first case to report UGIB due to a tortuous left inferior phrenic artery. This case highlights the limitations of endoscopy in identifying arterial abnormalities and emphasizes the potential of TAE as a viable alternative for the management of arterial bleeding in the gastrointestinal tract.

3.
Cereb Cortex ; 34(10)2024 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-39363728

RESUMEN

Alzheimer's disease is the most common major neurocognitive disorder. Although currently, no cure exists, understanding the neurobiological substrate underlying Alzheimer's disease progression will facilitate early diagnosis and treatment, slow disease progression, and improve prognosis. In this study, we aimed to understand the morphological changes underlying Alzheimer's disease progression using structural magnetic resonance imaging data from cognitively normal individuals, individuals with mild cognitive impairment, and Alzheimer's disease via a contrastive variational autoencoder model. We used contrastive variational autoencoder to generate synthetic data to boost the downstream classification performance. Due to the ability to parse out the nonclinical factors such as age and gender, contrastive variational autoencoder facilitated a purer comparison between different Alzheimer's disease stages to identify the pathological changes specific to Alzheimer's disease progression. We showed that brain morphological changes across Alzheimer's disease stages were significantly associated with individuals' neurofilament light chain concentration, a potential biomarker for Alzheimer's disease, highlighting the biological plausibility of our results.


Asunto(s)
Enfermedad de Alzheimer , Encéfalo , Disfunción Cognitiva , Progresión de la Enfermedad , Imagen por Resonancia Magnética , Humanos , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/patología , Femenino , Masculino , Anciano , Imagen por Resonancia Magnética/métodos , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/patología , Disfunción Cognitiva/fisiopatología , Proteínas de Neurofilamentos/metabolismo , Anciano de 80 o más Años , Biomarcadores , Persona de Mediana Edad
5.
Clin Nutr ESPEN ; 64: 215-220, 2024 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-39396704

RESUMEN

BACKGROUND & AIMS: The value of serum albumin might be underestimated, especially in cancer patients. We thus aimed to evaluate the association between serum albumin level at hospital admission and clinical outcomes in hospitalized patients with cancer. METHODS: This is a retrospective, cross-sectional, and real-world data analysis. Hospitalized adult patients with malignant cancer were recruited from two tertiary hospitals. Serum level of albumin, which was measured within 24 h after hospital admission, was the exposure. Length of hospital stays (LOS) was the primary and all-cause in-hospital mortality was the secondary outcomes. Other information, including age, sex, types of cancer, history of hypertension and diabetes, surgery, blood routine test, liver and renal function, and dietary intake, were also abstracted from medical records. RESULTS: A total number of 5187 adult patients with cancer (2949 were men and 2238 women; average age 61.6 ± 12.4 years and average albumin 40.3 ± 5.2 g/L) were included. The prevalence of hypoalbuminemia was 12.2 % (634/5187). Older patients, patients with liver injury, anemia, and with high level of WBC were positively, while those with overweight and high level of total triglycerides, were negatively associated with hypoalbuminemia. After adjustment of covariates, hypoalbuminemia was significantly associated with longer LOS in the current study. The increase of 5 g/L in serum level of albumin could result in 1.09 days (95%CI: -1.38, -0.80 days) shorter in LOS. The increase of 5 g/L in serum level of albumin was also associated with 45 % lower in risk of mortality (OR = 0.55; 95 % CI: 0.43, 0.7) after fully adjustment. CONCLUSIONS: Serum albumin level at admission was associated with both LOS and mortality in patients with malignant cancer.

6.
bioRxiv ; 2024 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-39416080

RESUMEN

Periodontitis disproportionately affects racial/ethnic populations. Besides social determinants contributing to disparities in periodontal health, variations of oral microbial communities may also be a key factor influencing oral immune responses. To characterize the oral microbiome from different racial/ethnic populations, we collected 161 dental plaque samples from African Americans (AAs), Caucasian Americans (CAs), and Hispanic Americans (HAs) with clinical gingival health or biofilm-induced gingivitis on an intact periodontium. Using metagenomic sequencing, we found significant difference in diversity and abundance of microbial taxa in the dental plaque samples from AA, CA, and HA groups and unique microbial species that can only be detected in a particular racial/ethnic group. Moreover, we revealed racial/ethnic associated variations in functional potential of the oral microbiome, showing that diversity and abundance of antibiotic resistant genes were greater in the oral microbiome of the AAs than those in CAs or HAs, and that the AAs exhibited higher levels of genes involving in modification of glycoconjugates, oligo- and polysaccharides. These findings indicate more complex and higher virulence potential oral microbiome in AA and HA populations, which likely contributes to higher prevalence of periodontitis in AAs and HAs. Importance: Recognizing the variations in the oral microbiome among racial/ethnic populations offers insight into the microbial determinants contributing to oral health disparities. In the study presented here, we found a higher level of bleeding on probing (BOP), an indicator of tissue inflammatory response, in the AA group, which is correspondence with a more complex oral microbiome detected in this group. Our observations suggest that the variations of the oral microbiome associated with racial/ethnic backgrounds may directly relate to their virulence potential including their abilities to induce host immune responses and to resist antibiotic treatment. Therefore, these finding can be a stepping stone for developing precision medicine and personalized periodontal prevention/treatment and for reducing oral health disparities.

7.
bioRxiv ; 2024 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-39416217

RESUMEN

BACKGROUND: Major depressive disorder (MDD) is a prevalent psychiatric disorder characterized by substantial clinical and neurobiological heterogeneity. Conventional studies that solely focus on clinical symptoms or neuroimaging metrics often fail to capture the intricate relationship between these modalities, limiting their ability to disentangle the complexity in MDD. Moreover, patient neuroimaging data typically contains normal sources of variance shared with healthy controls, which can obscure disorder-specific variance and complicate the delineation of disease heterogeneity. METHODS: We employed contrastive principal component analysis to extract disorder-specific variations in fMRI-based resting-state functional connectivity (RSFC) by contrasting MDD patients (N=233) with age-matched healthy controls (N=285). We then applied sparse canonical correlation analysis to identify latent dimensions in the disorder variations by linking the extracted contrastive connectivity features to clinical symptoms in MDD patients. RESULTS: Two significant and generalizable dimensions linking distinct brain circuits and clinical profiles were discovered. The first dimension, associated with an apparent internalizing-externalizing symptom dimension, was characterized by self-connections within the visual network and also associated with choice reaction times of cognitive tasks. The second dimension, associated with personality facets such as extraversion and conscientiousness typically inversely associated with depression symptoms, is primarily driven by self-connections within the dorsal attention network. This depression-protective personality dimension is also associated with multiple cognitive task performances related to psychomotor slowing and cognitive control. CONCLUSIONS: Our contrastive RSFC-based dimensional approach offers a new avenue to dissect clinical heterogeneity underlying MDD. By identifying two stable, neurophysiology-informed symptom dimensions in MDD patients, our findings may enhance disease mechanism insights and facilitate precision phenotyping, thus advancing the development of targeted therapeutics for precision mental health.

8.
Am J Hum Genet ; 2024 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-39419027

RESUMEN

Microtubule affinity-regulating kinase 2 (MARK2) contributes to establishing neuronal polarity and developing dendritic spines. Although large-scale sequencing studies have associated MARK2 variants with autism spectrum disorder (ASD), the clinical features and variant spectrum in affected individuals with MARK2 variants, early developmental phenotypes in mutant human neurons, and the pathogenic mechanism underlying effects on neuronal development have remained unclear. Here, we report 31 individuals with MARK2 variants and presenting with ASD, other neurodevelopmental disorders, and distinctive facial features. Loss-of-function (LoF) variants predominate (81%) in affected individuals, while computational analysis and in vitro expression assay of missense variants supported the effect of MARK2 loss. Using proband-derived and CRISPR-engineered isogenic induced pluripotent stem cells (iPSCs), we show that MARK2 loss leads to early neuronal developmental and functional deficits, including anomalous polarity and dis-organization in neural rosettes, as well as imbalanced proliferation and differentiation in neural progenitor cells (NPCs). Mark2+/- mice showed abnormal cortical formation and partition and ASD-like behavior. Through the use of RNA sequencing (RNA-seq) and lithium treatment, we link MARK2 loss to downregulation of the WNT/ß-catenin signaling pathway and identify lithium as a potential drug for treating MARK2-associated ASD.

9.
Seizure ; 122: 64-70, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39368329

RESUMEN

OBJECTIVE: The purpose of this study was to evaluate the performance and generalizability of an automated, interpretable surface-based MRI classifier for the detection of focal cortical dysplasia. METHODS: This was a retrospective cohort incorporating MRIs from the epilepsy surgery (FCD and MRI-negative) and neuroimaging (healthy controls) databases at Children's National Hospital (CNH), and a publicly-available FCD Type II dataset from Bonn, Germany. Clinical characteristics and outcomes were abstracted from patient records and/or existing databases. Subjects were included if they had 3T epilepsy-protocol MRI. Manually-segmented FCD masks were compared to the automated masks generated by the Multi-centre Epilepsy Lesion Detection (MELD) FCD detection algorithm. Sensitivity/specificity were calculated. RESULTS: From CNH, 39 FCD pharmacoresistant epilepsy (PRE) patients, 19 healthy controls, and 19 MRI-negative patients were included. From Bonn, 85 FCD Type II were included, of which 68 passed preprocessing. MELD had varying performance (sensitivity) in these datasets: CNH FCD-PRE (54 %); Bonn (68 %); MRI-negative (44 %). In multivariate regression, FCD Type IIB pathology predicted higher chance of MELD automated lesion detection. All four patients who underwent resection/ablation of MELD-identified clusters achieved Engel I outcome. SIGNIFICANCE: We validate the performance of MELD automated, interpretable FCD classifier in a diverse pediatric cohort with FCD-PRE. We also demonstrate the classifier has relatively good performance in an independent FCD Type II cohort with pediatric-onset epilepsy, as well as simulated real-world value in a pediatric population with MRI-negative PRE.

10.
J Int Med Res ; 52(9): 3000605241274576, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39225007

RESUMEN

OBJECTIVE: We developed a few-shot learning (FSL) framework for the diagnosis of osteopenia and osteoporosis in knee X-ray images. METHODS: Computer vision models containing deep convolutional neural networks were fine-tuned to enable generalization from natural images (ImageNet) to chest X-ray images (normal vs. pneumonia, base images). Then, a series of automated machine learning classifiers based on the Euclidean distances of base images were developed to make predictions for novel images (normal vs. osteopenia vs. osteoporosis). The performance of the FSL framework was compared with that of junior and senior radiologists. In addition, the gradient-weighted class activation mapping algorithm was used for visual interpretation. RESULTS: In Cohort #1, the mean accuracy (0.728) and sensitivity (0.774) of the FSL models were higher than those of the radiologists (0.512 and 0.448). A diagnostic pipeline of FSL model (first)-radiologists (second) achieved better performance (0.653 accuracy, 0.582 sensitivity, and 0.816 specificity) than radiologists alone. In Cohort #2, the diagnostic pipeline also showed improved performance. CONCLUSIONS: The FSL framework yielded practical performance with respect to the diagnosis of osteopenia and osteoporosis in comparison with radiologists. This retrospective study supports the use of promising FSL methods in computer-aided diagnosis tasks involving limited samples.


Asunto(s)
Enfermedades Óseas Metabólicas , Osteoporosis , Humanos , Osteoporosis/diagnóstico por imagen , Osteoporosis/diagnóstico , Enfermedades Óseas Metabólicas/diagnóstico por imagen , Enfermedades Óseas Metabólicas/diagnóstico , Femenino , Masculino , Persona de Mediana Edad , Anciano , Rodilla/diagnóstico por imagen , Rodilla/patología , Algoritmos , Redes Neurales de la Computación , Aprendizaje Automático , Radiografía/métodos , Adulto , Estudios Retrospectivos , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/patología , Diagnóstico por Computador/métodos
11.
Nat Ment Health ; 2(3): 287-298, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-39219688

RESUMEN

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder characterized by social and communication deficits (SCDs), restricted and repetitive behaviors (RRBs) and fixated interests. Despite its prevalence, development of effective therapy for ASD is hindered by its symptomatic and neurophysiological heterogeneities. To comprehensively explore these heterogeneities, we developed a new analytical framework combining contrastive learning and sparse canonical correlation analysis that identifies symptom-linked resting-state electroencephalographic connectivity dimensions within 392 ASD samples. We present two dimensions with multivariate connectivity basis exhibiting significant correlations with SCD and RRB, confirm their robustness through cross-validation and demonstrate their conceptual generalizability using an independent dataset (n = 222). Specifically, the right inferior parietal lobe is the core region for RRB, while connectivity between the left angular gyrus and the right middle temporal gyrus show key contribution to SCD. These findings provide a promising avenue to parse ASD heterogeneity with high clinical translatability, paving the way for ASD treatment development and precision medicine.

12.
Front Pediatr ; 12: 1409264, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39318621

RESUMEN

Background: CNV in KCTD13 has been identified to influence androgen receptor function via its changes in gene dosage, which might contribute to hypospadias. However, there is lack of population-level evidence to assess the contribution of KCTD13 CNV to hypospadias. Methods: 349 isolated hypospadias patients were recruited and their genotyping was performed using real-time qPCR. We use Database of Genomic Variants (DGV) and CNV calls from SNP-array intensity data in 1,008 Chinese healthy men as reference. Results: 11.17% of patients were identified to have KCTD13 CNV deletion, significantly higher than 0.05% in DGV (P < 0.001), but no cases found to have CNV duplication. Meanwhile, no CNV calls encompassing KCTD13 region were detected in Chinese healthy men. Incidence of KCTD13 CNV deletion was significantly increased with the severity of hypospadias, P _trend = 9.00 × 10-6. Compared to distal hypospadias, ORs for the proximal and midshaft were 10.07 (2.91-34.84) and 6.08 (1.69-21.84) respectively. In addition, the association between genital characteristics (stretched penile length and glans width) and KCTD13 CNV showed no significance in hypospadias children (P > 0.05). Conclusions: We demonstrate KCTD13 CNV deletion is strongly associated with hypospadias and its severity, but duplication is not, characterizing KCTD13 genetic variation in more detail than previously described.

13.
ACS Appl Mater Interfaces ; 16(40): 54539-54547, 2024 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-39324823

RESUMEN

Inhibiting the growth of lithium dendrites is crucial for battery safety. For separators, their favorable electrolyte wettability, uniform current density, and high ionic conductivity are beneficial for avoiding Li dendrite growth. In this work, we propose a separator (PA@COF/PP) by modifying a polypropylene separator with H3PO4-functionalized covalent organic frameworks. The uniform channels of the covalent organic frameworks and H3PO4 can homogenize the current and act as ionic conductors for efficient Li+ migration. The synthesized separator effectively suppresses the growth of lithium dendrites and improves the stability of the batteries. A symmetric cell with the PA@COF/PP separator exhibits a stable life span over 4000 hours at a high current density of 5 mA cm-2, compared to the commercial PP separator, which lasts only 159 hours. This work provides an efficient method and novel inspiration for the construction of dendrite-free lithium metal batteries.

14.
Nat Ment Health ; 2(4): 388-400, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-39279909

RESUMEN

Cocaine use disorder (CUD) is prevalent, and repetitive transcranial magnetic stimulation (rTMS) shows promise in reducing cravings. However, the association between a consistent CUD-specific functional connectivity signature and treatment response remains unclear. Here we identify a validated functional connectivity signature from functional magnetic resonance imaging to discriminate CUD, with successful independent replication. We found increased connectivity within the visual and dorsal attention networks and between the frontoparietal control and ventral attention networks, alongside reduced connectivity between the default mode and limbic networks in patients with CUD. These connections were associated with drug use history and cognitive impairments. Using data from a randomized clinical trial, we also established the prognostic value of these functional connectivities for rTMS treatment outcomes in CUD, especially involving the frontoparietal control and default mode networks. Our findings reveal insights into the neurobiological mechanisms of CUD and link functional connectivity biomarkers with rTMS treatment response, offering potential targets for future therapeutic development.

15.
Oncol Lett ; 28(5): 530, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39290955

RESUMEN

Breast cancer (BC) remains one of the most common malignant diseases affecting female patients, and it can metastasize to nearly every part of the body. BC is rare in men, and therefore men rarely develop BC liver metastases (BCLMs). However, the present study reports a 55-year-old male patient who underwent surgery 5 years ago for BC. After treatment, the patient was actively followed up regularly. Recently, the patient was examined for chest tightness, and liver space-occupying lesions were found. The upper abdominal enhanced computed tomography images of the patient showed that the liver density was not uniform and that the liver had a mass. A crude needle biopsy was used to examine the liver tumour under the guidance of ultrasound. The pathology revealed that the patient was positive for E-cadherin, oestrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, GATA binding protein 3 and CK7. The patient was subsequently diagnosed with BCLM. The patient was treated with doxorubicin hydrochloride, cyclophosphamide, Docetaxel and followed up regularly. The present case report emphasizes that BC is found not only in women but also in an increasing number of men, and that liver metastasis can occur in males with BC. BCLM is a complex process, and therefore it is hoped this case report will improve the understanding of male BCLM and the mechanism of this disease.

16.
Sci Rep ; 14(1): 19805, 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39191843

RESUMEN

The ecological benefits and concerns surrounding fossil fuels had led to increased interest in bio-based rigid polyurethane foam (RPUF). Nonetheless, due to its flammability, it had limited application in various fields. To solve this problem, a green bio-flame retardant, cobalt hydroxystannate (CoSn(OH)6), was prepared and compounded with montmorillonite (MMT) and chick feather protein (CF), and applied to RPUF, which not only realized the regeneration of resources, but also provided RPUF with better thermal stability, flame retardancy and smoke suppression properties. The experimental results showed that when 3 wt% CoSn(OH)6 was added, the RPUF (CF1/MMT3/Co3) had the greatest activation energy. In addition, the peak heat release rate (PHRR) and total heat release (THR) of CF1/MMT3/Co3 decreased by 12.73%, and 11.16% respectively, compared with no CoSn(OH)6. In addition, its Ds decreased by 28.9% and the light transmittance increased by 17.6% compared with the RPUF without CoSn(OH)6. At the same time, its peak smoke production rate (PSPR) and the total smoke release (TSR) decreased by 25% and 18%. And CF1/MMT3/Co3 also had the lowest fire risk evaluation index. This study presented possibilities for practical utilization of the RPUF substances founded on bio-based flame inhibitors.

17.
J Med Chem ; 67(17): 15816-15836, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39163619

RESUMEN

CCNE1 amplification occurs in breast cancer and currently lacks effective therapies. PKMYT1 as a synthetic lethal target for CCNE1 amplification holds promise for the treatment of CCNE1-amplified breast cancer. Herein, we discover a series of 2-amino-[1,1'-biphenyl]-3-carboxamide derivatives as potent and selective PKMYT1 inhibitors using structure-based drug design. The representative compound 8ma exhibited excellent potency against PKMYT1, while sparing WEE1. It also suppressed proliferation of the CCNE1-amplified HCC1569 breast cancer cell line and showed synergistic cytotoxicity in combination with gemcitabine. PKMYT1 X-ray cocrystallography confirmed that introduction of key binding interactions between the inhibitors and residues Asp251 and Tyr121 of PKMYT1 greatly enhanced the potency and selectivity of the compounds.


Asunto(s)
Antineoplásicos , Neoplasias de la Mama , Proliferación Celular , Ciclina E , Diseño de Fármacos , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Femenino , Relación Estructura-Actividad , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ciclina E/metabolismo , Proteínas Oncogénicas/antagonistas & inhibidores , Proteínas Oncogénicas/metabolismo , Proteínas Oncogénicas/genética , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/síntesis química , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Proteínas Tirosina Quinasas/metabolismo , Ensayos de Selección de Medicamentos Antitumorales , Cristalografía por Rayos X , Proteínas de la Membrana , Proteínas Serina-Treonina Quinasas
18.
Front Pharmacol ; 15: 1398953, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39135788

RESUMEN

Introduction: Sodium zirconium cyclosilicate (SZC) is a nonabsorbed cation-exchanger approved in China for the treatment of hyperkalemia [HK; serum potassium (sK+) levels >5.0 mmol/L]. This is the first real-world study aimed to assess the effectiveness, safety, and treatment patterns of SZC in Chinese patients with HK. Here we present the results of the first interim analysis. Methods: This multicenter, prospective, cohort study included patients aged ≥18 years with documented HK within 1-year before study enrollment day. These patients were followed up for 6 months from the enrollment day after initiating SZC treatment. The treatment was categorized into correction phase (FAS-P1) and maintenance phase (FAS-P2 new and ongoing users). Subgroup analysis was performed in patients on hemodialysis (FAS-H). The primary objective was evaluation of safety profile of SZC; secondary objectives included assessment of treatment patterns of SZC and its effectiveness. Results: Of 421 screened patients, 193, 354, and 162 patients were enrolled in the FAS-P1, FAS-P2, and FAS-H groups, respectively. sK+ levels were reduced significantly from 5.9 mmol/L to 5.0 mmol/L after the correction phase. For the maintenance phase, the mean sK+ levels were maintained at 5.2 mmol/L and 5.0 mmol/L in the FAS-P2 new and ongoing user, respectively, and 5.3 mmol/L in the FAS-H subgroup. A considerable proportion of patients showed normokalemia after 48 h of SZC treatment (FAS-P1:51.3%) which was maintained up to 6 months in the maintenance phase (FAS-P2:44%). SZC was well-tolerated. Conclusion: SZC was effective and safe for the treatment of HK in real-world clinical practice in China.

19.
Anal Chim Acta ; 1320: 342993, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39142777

RESUMEN

BACKGROUND: Bisulfite (HSO3-) serves as a bleaching agent, antioxidant, antimicrobial, and regulator of enzymatic reactions in biosystem. However, abnormal levels of bisulfite can be detrimental to health. Hypochlorous acid (HOCl), which acts as bioactive small molecules, is crucial for maintaining normal biological functions in living organisms. Disruption of its equilibrium can lead to oxidative stress and various diseases. Therefore, it's essential to monitor the fluctuations of HOCl and HSO3- at cellular and in vivo levels to study their physiological and pathological functions. RESULTS: This study constructed a novel NIR bifunctional colorimetric fluorescent probe using thienocoumarin-indanedione structures to identify hypochlorite (ClO-) and bisulfite (HSO3-). By using CSO-IO to recognize HSO3- and HOCl, two distinct products were generated, displaying green and blue fluorescence, respectively. This property effectively allows for the simultaneous dual-functional detection of HSO3- (LOD: 113 nM) and HOCl (LOD: 43 nM). SIGNIFICANCE: In this work, the biocompatible molecule CSO-IO has been effectively designed to detect HOCl/HSO3- in living cells and zebrafish. As a result, the dual-functional fluorescent probe has the potential to be utilized as a molecular tool to detect HSO3- derived compounds and HOCl simultaneously within the complex biological system.


Asunto(s)
Colorantes Fluorescentes , Ácido Hipocloroso , Sulfitos , Pez Cebra , Ácido Hipocloroso/análisis , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Sulfitos/análisis , Sulfitos/química , Animales , Humanos , Imagen Óptica , Rayos Infrarrojos , Ratones
20.
Ecotoxicol Environ Saf ; 282: 116836, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39097417

RESUMEN

Since the onset of the SARS-CoV-2 pandemic in early 2020, there has been a notable rise in sodium hypochlorite disinfectants. Sodium hypochlorite undergoes hydrolysis to generate hypochlorous acid for virus eradication. This chlorine-based disinfectant is widely utilized for public disinfection due to its effectiveness. Although sodium hypochlorite disinfection is convenient, its excessive and indiscriminate use can harm the water environment and pose a risk to human health. Hypochlorous acid, a reactive oxygen species, plays a crucial role in the troposphere, stratospheric chemistry, and oxidizing capacity. Additionally, hypochlorous acid is vital as a reactive oxygen species in biological systems, and its irregular metabolism and level is associated with several illnesses. Thus, it is crucial to identify hypochlorous acid to comprehend its environmental and biological functions precisely. Here, we constructed a new fluorescent probe, utilizing the twisted intramolecular charge transfer mechanism to quickly and accurately detect hypochlorous acid in environmental water and biosystems. The probe showed a notable increase in fluorescence when exposed to hypochlorous acid, demonstrating its excellent selectivity, fast response time (less than 10 seconds), a large Stokes shift (∼ 102 nm), and a low detection limit of 15.5 nM.


Asunto(s)
Cumarinas , Colorantes Fluorescentes , Ácido Hipocloroso , Contaminantes Químicos del Agua , Ácido Hipocloroso/química , Colorantes Fluorescentes/química , Cumarinas/química , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/química , Contaminantes Químicos del Agua/toxicidad , Animales , Desinfectantes/química , Desinfectantes/análisis , Desinfectantes/toxicidad , Límite de Detección
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