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2.
Alzheimers Dement ; 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38958394

RESUMEN

INTRODUCTION: Sodium-glucose cotransporter 2 (SGLT2) inhibitors exhibit potential benefits in reducing dementia risk, yet the optimal beneficiary subgroups remain uncertain. METHODS: Individuals with type 2 diabetes (T2D) initiating either SGLT2 inhibitor or sulfonylurea were identified from OneFlorida+ Clinical Research Network (2016-2022). A doubly robust learning was deployed to estimate risk difference (RD) and 95% confidence interval (CI) of all-cause dementia. RESULTS: Among 35,458 individuals with T2D, 1.8% in the SGLT2 inhibitor group and 4.7% in the sulfonylurea group developed all-cause dementia over a 3.2-year follow-up, yielding a lower risk for SGLT2 inhibitors (RD, -2.5%; 95% CI, -3.0% to -2.1%). Hispanic ethnicity and chronic kidney disease were identified as the two important variables to define four subgroups in which RD ranged from -4.3% (-5.5 to -3.2) to -0.9% (-1.9 to 0.2). DISCUSSION: Compared to sulfonylureas, SGLT2 inhibitors were associated with a reduced risk of all-cause dementia, but the association varied among different subgroups. HIGHLIGHTS: New users of sodium-glucose cotransporter 2 (SGLT2) inhibitors were significantly associated with a lower risk of all-cause dementia as compared to those of sulfonylureas. The association varied among different subgroups defined by Hispanic ethnicity and chronic kidney disease. A significantly lower risk of Alzheimer's disease and vascular dementia was observed among new users of SGLT2 inhibitors compared to those of sulfonylureas.

3.
Int J Biol Macromol ; : 133704, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38972655

RESUMEN

To identify the key amino acids (AAs) affecting the allergenicity of hemocyanin (HC) allergens from Chinese mitten crabs, in this study, two epitopes, P1-SHFTGSKSNPEQR and P2-LSPGANTITR were employed and four potential key AAs (P1: F3 and N9 and P2: N6 and R10) were predicted. Mast cell and mouse models revealed that four mutants induced lower levels of Immunoglobulin E (IgE) and Th2 type cytokines (15.47-49.89 %), proving that F3, N9, N6, and R10 were the key AAs of two epitopes. Mutants reduce allergic responses via the Th2 pathway. However, the roles of every key AA affecting allergenicity were different (P1-F3 > N9 and P2-N6 > R10). In addition, lower transport and higher efflux were observed in the mutants during transport absorption by Caco-2 cells. The allergenicity of HC was stronger when the transport absorption efficiency of epitopes and mutants was higher and their efflux was lower. Our study provides a novel method for revealing the allergenic molecular mechanisms of food allergens.

4.
iScience ; 27(6): 109931, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38974470

RESUMEN

Large prospective studies are required to better elucidate the associations of physical activity, sedentary behaviors (SBs), and sleep with overall cancer and site-specific cancer risk, accounting for the interactions with genetic predisposition. The study included 360,271 individuals in UK Biobank. After a median follow-up of 12.52 years, we found higher total physical activity (TPA) level and higher sleep scores were related to reduced risk of cancer while higher SB level showed a positive association with cancer. Compared with high TPA-healthy sleep group and low SB-healthy sleep group, low TPA-poor sleep group and high SB-poor sleep group had the highest risk for overall cancer, breast cancer, and lung cancer. Adherence to a more active exercise pattern was associated with a lower risk of cancer irrespective of genetic risk. Our study suggests that improving the quality of sleep and developing physical activity habits might yield benefits in mitigating the cancer risk.

5.
Medicine (Baltimore) ; 103(26): e38700, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38941382

RESUMEN

This study aims to critically reassess existing systematic reviews (SR) on Traditional Chinese Exercises (TCE) for treating Chronic Obstructive Pulmonary Disease (COPD). The primary objectives include synthesizing available evidence, evaluating the methodological quality of reviews and overall evidence, and providing comprehensive insights into the effectiveness of different TCE types in managing COPD. Sinomed, CNKI, VIP, Wanfang, PubMed, Cochrane Library, and Web of Science were searched from inception to April 2023 for SR literature on the treatment of COPD with TCE. The extracted data from the included SRs encompassed various aspects such as general information, study population, intervention measures, meta-analysis results, and conclusions. The methodological quality of the included SRs was assessed using the AMSTAR II tool. Additionally, the GRADE tool was used to determine the evidence level of outcome indicators. This study included 17 SRs and 4 types of TCE. The CCA was 0.041, indicating a slight overlap between the primary studies. Notably, one study was rated as low quality on the AMSTAR II scale, while the rest were classified as critically low quality. The results from the GRADE evaluation revealed 26 pieces of very low-quality evidence, 55 pieces of low-quality evidence, and 17 pieces of moderate-quality evidence. The moderate-quality evidence suggests that Liuzijue effectively improves TCM syndrome scores in patients with COPD. Additionally, low-quality evidence suggests that Liuzijue improves patients' lung function (FEV1, FVC) and quality of life (CAT, MRC/mMRC). Similarly, low-quality evidence suggests that Baduanjin can improve patients' lung function (FEV1%, FVC) and quality of life (SGRQ). Low-quality evidence also suggests that Health Qigong can significantly improve patients' exercise endurance (6MWD). No SR reported TCE-related adverse reactions. TCE interventions are effective and safe in the treatment of COPD. Different types of TCE have varying effects on outcomes in COPD patients. However, these findings are limited by the generally low methodological and evidence quality of the included SRs. Therefore, it is strongly recommended to improve study designs to obtain higher-quality clinical evidence and to strictly follow SR protocols.


Asunto(s)
Medicina Tradicional China , Enfermedad Pulmonar Obstructiva Crónica , Revisiones Sistemáticas como Asunto , Enfermedad Pulmonar Obstructiva Crónica/terapia , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/rehabilitación , Humanos , Medicina Tradicional China/métodos , Terapia por Ejercicio/métodos , Calidad de Vida , Qigong/métodos , Pueblos del Este de Asia
6.
J Phys Chem C Nanomater Interfaces ; 128(24): 10084-10107, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38919725

RESUMEN

All-inorganic metal halide perovskite nanocrystals (PeNCs) show great potential for the next generation of perovskite light-emitting diodes (PeLEDs). However, trap-assisted recombination negatively impacts the optoelectronic properties of PeNCs and prevents their widespread adoption for commercial exploitation. To mitigate trap-assisted recombination and further enhance the external quantum efficiency of PeLEDs, A/B-site doping has been widely investigated to tune the bandgap of PeNCs. The bandgap of PeNCs is adjustable within a small range (no more than 0.1 eV) by A-site cation doping, resulting in changes in the bond length of Pb-X and the angle of [PbX6]4. Nevertheless, B-site doping of PeNCs has a more significant impact on the bandgap level through modification of surface defect states. In this perspective, we delve into the synthesis of PeNCs with A/B-site doping and their impacts on the structural and optoelectronic properties, as well as their impacts on the performance of subsequent PeLEDs. Furthermore, we explore the A-site and B-site doping mechanisms and the impact of device architecture on doped PeNCs to maximize the performance and stability of PeLEDs. This work presents a comprehensive overview of the studies on A-site and B-site doping in PeNCs and approaches to unlock their full potential in the next generation of LEDs.

7.
J Inflamm Res ; 17: 3515-3525, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38836244

RESUMEN

Objective: To evaluate the safety and feasibility of tonsillectomy and/or adenoidectomy (T&A) in pediatric patients with prolonged activated partial thromboplastin time (APTT) and coagulation factor deficiency. Methods: A prospective study was admitted to the children undergoing T&A at our institution between October 2019 and January 2020, specifically focusing on preoperative coagulation function. Within this group, we identified 5 patients exhibiting prolonged APTT and coagulation factor deficiencies, constituting the experimental group, and 10 patients matched by gender and age with normal blood coagulation function were selected as the control group. Comparative analyses between the two groups were conducted, focusing on surgical duration, intraoperative bleeding volume, duration of hospital stay, and postoperative complications such as active bleeding across the groups. At the six-month postoperative mark, a reassessment of coagulation functions and factor assays was conducted within the experimental group. Results: No statistically significant differences were discovered in terms of surgical duration or bleeding volume when comparing the experimental subgroups with their respective control counterparts. Furthermore, there were no incidences of postoperative active bleeding observed in any of the groups. Notably, postoperative APTT values (32.7 ± 1.7s) exhibited a significant disparity compared to preoperative levels (43.7 ± 1.8s, p < 0.01). Coagulation factors demonstrated normalization, evidenced by a significant difference in postoperative Factor XII levels (40.2 ± 5.4%) compared to preoperative levels (63.1 ± 5.9%, p < 0.01). Conclusion: Prolonged APTT with FXII factor deficiency does not show a significant bleeding tendency and is not a contraindication for T&A surgery. Post T&A surgery, children with abnormal coagulation function and deficient clotting factors show significant improvement compared to pre-surgery. It is important to consider that chronic inflammation in adenoids and tonsils may contribute to the prolongation of APTT and the manifestation of Factor XII deficiency.

8.
Front Immunol ; 15: 1374390, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38868768

RESUMEN

Immunotherapy for hematological malignancies is a rapidly advancing field that has gained momentum in recent years, primarily encompassing chimeric antigen receptor T-cell (CAR-T) therapies, immune checkpoint inhibitors, and other modalities. However, its clinical efficacy remains limited, and drug resistance poses a significant challenge. Therefore, novel immunotherapeutic targets and agents need to be identified. Recently, N6-methyladenosine (m6A), the most prevalent RNA epitope modification, has emerged as a pivotal factor in various malignancies. Reportedly, m6A mutations influence the immunological microenvironment of hematological malignancies, leading to immune evasion and compromising the anti-tumor immune response in hematological malignancies. In this review, we comprehensively summarize the roles of the currently identified m6A modifications in various hematological malignancies, with a particular focus on their impact on the immune microenvironment. Additionally, we provide an overview of the research progress made in developing m6A-targeted drugs for hematological tumor therapy, to offer novel clinical insights.


Asunto(s)
Adenosina , Neoplasias Hematológicas , Microambiente Tumoral , Humanos , Microambiente Tumoral/inmunología , Neoplasias Hematológicas/inmunología , Neoplasias Hematológicas/terapia , Adenosina/análogos & derivados , Adenosina/inmunología , Adenosina/metabolismo , Animales , Inmunoterapia/métodos
9.
Neurology ; 103(2): e209502, 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-38875513

RESUMEN

BACKGROUND AND OBJECTIVES: The Patient-Ranked Order of Function (PROOF) is a novel approach to account for patient-reported preferences in the evaluation of treatments of amyotrophic lateral sclerosis (ALS). In this study, we assess the reliability and prognostic value of different sets of patient-reported preferences that can be used for the PROOF end point. METHODS: Data were obtained through online surveys over the course of 12 months using the population-based registry of the Netherlands. Patients were asked to score functional domains of the ALS Functional Rating Scale (ALSFRS-R) and rank the order of importance of each domain. Two weeks after the initial invite, the questionnaire was repeated to evaluate test-retest reliability. Vital status was extracted from the municipal population register. RESULTS: In total, 611 patients with ALS were followed up for survival and 382 patients were included in the test-retest reliability study. All versions of PROOF, using different sets of preferences, resulted in excellent reliability (intraclass correlation coefficients ranged from 0.89 [95% CI 0.87-0.91] to 0.97 [95% CI 0.97-0.98], all p < 0.001), without systematic differences between baseline and week 2 (mean rank difference range -1 to -3 [95% CI range -8 to 2], all p > 0.20). Preferences about future events were more variable than preferences about current symptoms. All versions of PROOF strongly predicted overall survival (hazard ratios per 10th rank percentile ranged from 0.80 to 0.83 [95% CI range 0.76-0.87], all p < 0.001) and had a more even separation of survival curves between rank-stratified subgroups compared with the ALSFRS-R total score. DISCUSSION: In a large cohort of patients, we show how patient-reported preferences can be measured and integrated reliably with the ALSFRS-R without leading to systematic bias. Patient preferences may provide unique prognostic information in addition to what is already measured conventionally. This could provide a more comprehensive understanding of how medical interventions effectively address the patient's concerns and improve what matters most to them.


Asunto(s)
Esclerosis Amiotrófica Lateral , Prioridad del Paciente , Humanos , Esclerosis Amiotrófica Lateral/terapia , Esclerosis Amiotrófica Lateral/diagnóstico , Esclerosis Amiotrófica Lateral/fisiopatología , Masculino , Femenino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Pronóstico , Anciano , Países Bajos , Ensayos Clínicos como Asunto , Encuestas y Cuestionarios , Sistema de Registros
10.
Sci Data ; 11(1): 629, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38877023

RESUMEN

The Chungtien schizothoracin (Ptychobarbus chungtienensis), an endangered fish species endemic to the Zhongdian Plateau, remains underexplored in terms of transcriptomic sequencing. This investigation used tissues from five distinct organs (heart, liver, spleen, kidney, and brain) of the Chungtien schizothoracin for PacBio Iso-seq and RNA-seq analyses, yielding a repertoire of 16,598 full-length transcripts spanning lengths from 363 bp to 7,157 bp. Gene family clustering and phylogenetic analysis encompassed a comprehensive set of 13 fish species, all of which were cyprinids, including the zebrafish and the examined species Ptychobarbus chungtienensis. Moreover, the identification of long non-coding RNAs (lncRNAs) and coding sequences was accomplished across all five tissues. Comprehensive analyses of gene expression profiles and differentially expressed genes among the above five tissues were performed. In summary, the obtained full-length transcripts and detailed gene expression profiles of the Chungtien schizothoracin tissues furnish crucial expression data and genetic sequences, laying the groundwork for future investigations and fostering a holistic comprehension of the adaptive mechanisms inherent in the Chungtien schizothoracin under various conditions.


Asunto(s)
Cyprinidae , Filogenia , Transcriptoma , Animales , Cyprinidae/genética , RNA-Seq , ARN Largo no Codificante/genética , Especies en Peligro de Extinción
11.
Nat Commun ; 15(1): 5113, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38879529

RESUMEN

Factor-dependent termination uses molecular motors to remodel transcription machineries, but the associated mechanisms, especially in eukaryotes, are poorly understood. Here we use single-molecule fluorescence assays to characterize in real time the composition and the catalytic states of Saccharomyces cerevisiae transcription termination complexes remodeled by Sen1 helicase. We confirm that Sen1 takes the RNA transcript as its substrate and translocates along it by hydrolyzing multiple ATPs to form an intermediate with a stalled RNA polymerase II (Pol II) transcription elongation complex (TEC). We show that this intermediate dissociates upon hydrolysis of a single ATP leading to dissociation of Sen1 and RNA, after which Sen1 remains bound to the RNA. We find that Pol II ends up in a variety of states: dissociating from the DNA substrate, which is facilitated by transcription bubble rewinding, being retained to the DNA substrate, or diffusing along the DNA substrate. Our results provide a complete quantitative framework for understanding the mechanism of Sen1-dependent transcription termination in eukaryotes.


Asunto(s)
Adenosina Trifosfato , ADN Helicasas , ARN Polimerasa II , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Imagen Individual de Molécula , Terminación de la Transcripción Genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , ARN Polimerasa II/metabolismo , Adenosina Trifosfato/metabolismo , ADN Helicasas/metabolismo , ADN Helicasas/genética , Imagen Individual de Molécula/métodos , ARN Helicasas/metabolismo , ARN Helicasas/genética , Transcripción Genética , ARN de Hongos/metabolismo , ARN de Hongos/genética , ADN de Hongos/metabolismo , ADN de Hongos/genética , Hidrólisis
12.
ACS Omega ; 9(23): 24593-24600, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38882078

RESUMEN

This study synthesized core/shell gold-platinum nanoparticles and characterized their colorimetric properties; ultraviolet-visible spectroscopy revealed that the synthesized nanoparticles exhibited distinct colors from conventional gold nanoparticles. Furthermore, the nanoparticles were subjected to lateral flow assays using Protein A, and the results revealed that they outperformed conventional spherical gold nanoparticles in terms of color development. This improvement can be attributed to the distinct core/shell structures of our nanoparticles. Further evaluation revealed that these nanoparticles could facilitate the detection of Clostridium difficile Toxin B visually at an extremely low concentration (1 ng/mL) without the requirement for advanced instrumentation. This substantial improvement in sensitivity can be attributed to the meticulous design and nanoscale engineering of the structure of the nanoparticles.

13.
ACS Omega ; 9(23): 25215-25222, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38882146

RESUMEN

In exploring the viability of perovskite solar cells (PSCs) for Mars missions, our study first delved into their temperature endurance in conditions mimicking the Martian climate, revealing remarkable thermal stability within the temperature range of 173-303 K. We then pioneered the examination of PSC resilience to electrostatic discharge (ESD), a critical factor given the frequent Martian dust activities. In a custom-built Martian simulation chamber, we discovered that ESD exposure dramatically reduced the power conversion efficiency of these devices by more than half (55.4%) in just 90 s. This groundbreaking research not only advances our understanding of the potential of PSCs for Mars exploration but also opens new avenues for optimizing solar technology in extreme environments.

14.
Nutrients ; 16(11)2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38892643

RESUMEN

BACKGROUND: A gut-microbial metabolite, trimethylamine N-oxide (TMAO), has been associated with type 2 diabetes mellitus (T2DM). Few previous prospective studies have addressed associations between the changes in TMAO and T2DM incidence. METHODS: Data were derived from a longitudinal cohort conducted from 2019 to 2021 in rural areas of Fuxin County, Liaoning Province, China, and 1515 diabetes-free participants aged above 35 years were included. The concentrations of serum TMAO and its precursors were measured at two time points, namely in 2019 and 2021. TMAO and TMAO changes (ΔTMAO) were separately tested in a logistic regression model. For further examination, the odds ratios (ORs) for T2DM were calculated according to a combination of TMAO levels and ΔTMAO levels. RESULTS: During a median follow-up of 1.85 years, 81 incident cases of T2DM (5.35%) were identified. Baseline TMAO levels exhibited a nonlinear relationship, first decreasing and then increasing, and only at the highest quartile was it associated with the risk of T2DM. The OR for T2DM in the highest quartile of serum TMAO was 3.35 (95%CI: 1.55-7.26, p = 0.002), compared with the lowest quartile. As for its precursors, only choline level was associated with T2DM risk and the OR for T2DM in the Q3 and Q4 of serum choline was 3.37 (95%CI: 1.41-8.05, p = 0.006) and 4.72 (95%CI: 1.47-15.13, p = 0.009), respectively. When considering both baseline TMAO levels and ΔTMAO over time, participants with sustained high TMAO levels demonstrated a significantly increased risk of T2DM, with a multivariable-adjusted OR of 8.68 (95%CI: 1.97, 38.34). CONCLUSION: Both initial serum TMAO levels and long-term serum TMAO changes were collectively and significantly associated with the occurrence of subsequent T2DM events. Interventions aimed at normalizing TMAO levels, such as adopting a healthy dietary pattern, may be particularly beneficial in T2DM prevention.


Asunto(s)
Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Metilaminas , Humanos , Diabetes Mellitus Tipo 2/prevención & control , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/epidemiología , Metilaminas/sangre , Femenino , Masculino , Persona de Mediana Edad , Estudios Longitudinales , China/epidemiología , Adulto , Factores de Riesgo , Dieta , Estudios Prospectivos , Incidencia , Anciano , Colina/sangre
15.
Clin Med Insights Case Rep ; 17: 11795476241262213, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38895742

RESUMEN

Background: Cerebral infarct associated with varicella-zoster virus (VZV) has been reported in the literature, while isolated central dizziness due to lateral medullary infarct (LMI) following VZV infection is rarely reported. Case report: We report the case of a 65-year-old man who presented to the neurology department because of herpes zoster on the right trigeminal nerve distribution. At 12 hours after admission, he developed transient vertigo along with nausea and unsteady walking and left-sided spontaneous horizontal nystagmus, gaze-evoked nystagmus, and upbeat nystagmus. The other usual signs of LMI including Horner syndrome, dysarthria, swallowing difficulty, and hemibody sensory change were absent. Video head impulse indicated decreased head impulse gain of the vestibulo-ocular reflex for the bilateral horizontal, anterior, and posterior semicircular canals with abnormal saccade waves. Suppression head impulse paradigm showed few downward saccades reflecting anti-compensatory saccades after the end of the head impulse back to the head-fixed target and decreased vestibulo-ocular reflex gain values of bilateral semicircular canals. Brain magnetic resonance imaging (MRI) showed a small infarct in the far dorsolateral portion of the left rostral medulla. The cerebrospinal fluid was positive for VZV DNA. Conclusions: In patients with VZV infection who develop dizziness, the possibility of cerebral infarct should be considered. Patients with facial herpes zoster and neurological symptoms always be screened for stroke using MRI and lumbar puncture should be performed and acyclovir administered empirically.

16.
Bioorg Chem ; 149: 107500, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38823310

RESUMEN

This study aimed to develop the first dual-target small molecule inhibitor concurrently targeting Discoidin domain receptor 1 (DDR1) and Epidermal growth factor receptor (EGFR), which play a crucial interdependent roles in non-small cell lung cancer (NSCLC), demonstrating a synergistic inhibitory effect. A series of innovative dual-target inhibitors for DDR1 and EGFR were discovered. These compounds were designed and synthesized using structural optimization strategies based on the lead compound BZF02, employing 4,6-pyrimidine diamine as the core scaffold, followed by an investigation of their biological activities. Among these compounds, D06 was selected and showed micromolar enzymatic potencies against DDR1 and EGFR. Subsequently, compound D06 was observed to inhibit NSCLC cell proliferation and invasion. Demonstrating acceptable pharmacokinetic performance, compound D06 exhibited its anti-tumor activity in NSCLC PC-9/GR xenograft models without apparent toxicity or significant weight loss. These collective results showcase the successful synthesis of a potent dual-targeted inhibitor, suggesting the potential therapeutic efficacy of co-targeting DDR1 and EGFR for DDR1/EGFR-positive NSCLC.


Asunto(s)
Antineoplásicos , Carcinoma de Pulmón de Células no Pequeñas , Proliferación Celular , Receptor con Dominio Discoidina 1 , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Receptores ErbB , Neoplasias Pulmonares , Inhibidores de Proteínas Quinasas , Humanos , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/metabolismo , Receptor con Dominio Discoidina 1/antagonistas & inhibidores , Receptor con Dominio Discoidina 1/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Proliferación Celular/efectos de los fármacos , Relación Estructura-Actividad , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/síntesis química , Animales , Estructura Molecular , Ratones , Descubrimiento de Drogas , Ratones Desnudos , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/patología , Neoplasias Experimentales/metabolismo , Línea Celular Tumoral , Ratones Endogámicos BALB C
17.
Front Immunol ; 15: 1309447, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38855105

RESUMEN

Introduction: Lupus nephritis (LN), a severe complication of systemic lupus erythematosus (SLE), presents significant challenges in patient management and treatment outcomes. The identification of novel LN-related biomarkers and therapeutic targets is critical to enhancing treatment outcomes and prognosis for patients. Methods: In this study, we analyzed single-cell expression data from LN (n=21) and healthy controls (n=3). A total of 143 differentially expressed genes were identified between the LN and control groups. Then, proteomics analysis of LN patients (n=9) and control (SLE patients without LN, n=11) revealed 55 differentially expressed genes among patients with LN and control group. We further utilizes protein-protein interaction network and functional enrichment analyses to elucidate the pivotal role of COL6A3 in key signaling pathways. Its diagnostic value is evaluate through its correlation with disease progression and renal function metrics, as well as Receiver Operating Characteristic Curve (ROC) analysis. Additionally, immunohistochemistry and qPCR experiments were performed to validate the expression of COL6A3 in LN. Results: By comparison of single-cell and proteomics data, we discovered that COL6A3 is significantly upregulated, highlighting it as a critical biomarker of LN. Our findings emphasize the substantial involvement of COL6A3 in the pathogenesis of LN, particularly noting its expression in mesangial cells. Through comprehensive protein-protein interaction network and functional enrichment analyses, we uncovered the pivotal role of COL6A3 in key signaling pathways including integrin-mediated signaling pathways, collagen-activated signaling pathways, and ECM-receptor interaction, suggesting potential therapeutic targets. The diagnostic utility is confirmed by its correlation with disease progression and renal function metrics of the glomerular filtration rate. ROC analysis further validates the diagnostic value of COL6A3, with the area under the ROC values of 0.879 in the in-house cohort, and 0.802 and 0.915 in tubular and glomerular external cohort samples, respectively. Furthermore, immunohistochemistry and qPCR experiments were consistent with those obtained from the single-cell RNA sequencing and proteomics studies. Discussion: These results proved that COL6A3 is a promising biomarker and therapeutic target, advancing personalized medicine strategies for LN.


Asunto(s)
Biomarcadores , Colágeno Tipo VI , Nefritis Lúpica , Proteómica , Análisis de la Célula Individual , Humanos , Nefritis Lúpica/genética , Nefritis Lúpica/metabolismo , Colágeno Tipo VI/genética , Colágeno Tipo VI/metabolismo , Proteómica/métodos , Femenino , Adulto , Masculino , Transcriptoma , Mapas de Interacción de Proteínas , Perfilación de la Expresión Génica
18.
Chin J Integr Med ; 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38910189

RESUMEN

OBJECTIVE: To examine the effectiveness of Chinese medicine (CM) Lianhua Qingwen Granule (LHQW) and Jingyin Gubiao Prescription (JYGB) in asymptomatic or mild patients with Omicron infection in the shelter hospital. METHODS: This single-center retrospective cohort study was conducted in the largest shelter hospital in Shanghai, China, from April 10, 2022 to May 30, 2022. A total of 56,244 asymptomatic and mild Omicron cases were included and divided into 4 groups, i.e., non-administration group (23,702 cases), LHQW group (11,576 cases), JYGB group (12,112 cases), and dual combination of LHQW and JYGB group (8,854 cases). The length of stay (LOS) in the hospital was used to assess the effectiveness of LHQW and JYGB treatment on Omicron infection. RESULTS: Patients aged 41-60 years, with nadir threshold cycle (CT) value of N gene <25, or those fully vaccinated preferred to receive CM therapy. Before or after propensity score matching (PSM), the multiple linear regression showed that LHQW and JYGB treatment were independent influence factors of LOS (both P<0.001). After PSM, there were significant differences in LOS between the LHQW/JYGB combination and the other groups (P<0.01). The results of factorial design ANOVA proved that the LHQW/JYGB combination therapy synergistically shortened LOS (P=0.032). CONCLUSIONS: Patients with a nadir CT value <25 were more likely to accept CM. The LHQW/JYGB combination therapy could shorten the LOS of Omicron-infected individuals in an isolated environment.

19.
Bioresour Technol ; 405: 130936, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38851597

RESUMEN

Microbial fuel cell (MFC) is a promising device for water decontamination and energy generation. However, the correlation between power generation and pollutant degradation has not been clarified. Herein, a ruthenium-activated carbon (Ru-AC) bioanode was constructed for chlorobenzenes (CBs) treatment. The pollutant tolerance was improved by Ru-AC anode, and the minimum removal efficiencies of CB and ortho-dichlorobenzene (o-DCB) reached 75.1 % and 69.3 %, respectively, which were considerably higher than those of other MFCs (16.3 %-39.7 %). Correspondingly, the maximum output voltage reached 360.7 mV for the Ru-AC anode, whereas the values obtained from others reached 45.2-149.6 mV. Interaction models were introduced to quantify the relationship between power generation and pollutant degradation. The conversion of highly toxic chlorophenols to organic acids could be accelerated by boosting the mass and electron transfer, thereby simultaneously enhancing CBs removal and power generation. This work provided important insights into pollutant-powered MFC development.


Asunto(s)
Fuentes de Energía Bioeléctrica , Clorobencenos , Electrodos , Cinética , Contaminantes Químicos del Agua , Rutenio/química , Carbón Orgánico/química , Carbón Orgánico/farmacología , Biodegradación Ambiental , Purificación del Agua/métodos
20.
Angew Chem Int Ed Engl ; : e202407661, 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38924201

RESUMEN

Electrocatalytic reduction of CO2 powered by renewable electricity provides an elegant route for converting CO2 into valuable chemicals and feedstocks, but normally suffers from a high overpotential and low selectivity. Herein, Ag and Sn heteroatoms were simultaneously introduced into nanoporous Cu (np-Ag/Sn-Cu) mainly in the form of an asymmetric local electric field for CO2 electroreduction to CO in an aqueous solution. The designed np-Ag/Sn-Cu catalyst realizes a recorded 90% energy efficiency and a 100% CO Faradaic efficiency over ultrawide potential window (ΔE = 1.4 V), outperforming state-of-the-art Au and Ag-based catalysts. Density functional theory calculations combined with in situ spectroscopy studies reveal that Ag and Sn heteroatoms incorporated into Cu matrix could generate strong and asymmetric local electric field, which promotes the activation of CO2 molecules, enhances the stabilization of the *COOH intermediate, and suppresses the hydrogen evolution reaction, thus favoring the production of CO during CO2RR.

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