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1.
Natl Sci Rev ; 11(6): nwad103, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38725935

RESUMEN

Non-centrosymmetric topological material has attracted intense attention due to its superior characteristics as compared with the centrosymmetric one, although probing the local quantum geometry in non-centrosymmetric topological material remains challenging. The non-linear Hall (NLH) effect provides an ideal tool to investigate the local quantum geometry. Here, we report a non-centrosymmetric topological phase in ZrTe5, probed by using the NLH effect. The angle-resolved and temperature-dependent NLH measurement reveals the inversion and ab-plane mirror symmetries breaking at <30 K, consistently with our theoretical calculation. Our findings identify a new non-centrosymmetric phase of ZrTe5 and provide a platform to probe and control local quantum geometry via crystal symmetries.

2.
Water Res ; 257: 121743, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38728775

RESUMEN

Effective deep-dewatering is crucial for wastewater sludge management. Currently, the dominant methods focus on promoting cell lysis to release intracellular water, but these techniques often lead to secondary pollution and require stringent conditions, limiting their practical use. This study explores an innovative method using a commercially available complex quaternary ammonium salt surfactant, known as G-agent. This agent remarkably reduces the sludge water content from 98.6 % to 56.8 % with a low dosage (50 mg/g DS) and under neutral pH conditions. This approach surpasses Fenton oxidation in terms of dewatering efficiency and avoids the necessity for cell lysis and bound water release, thereby reducing the risk of secondary pollution in the filtrate, including heavy metals, nitrogen, phosphorus, and other contaminants. The G-agent plays a significant role in destabilizing flocs and enhancing flocculation during the conditioning and initial dewatering stages, effectively reducing the solid-liquid interfacial affinity of the sludge. In the compression filtration stage, the agent's solidification effect is crucial in forming a robust skeleton that improves pore connectivity within the filter cake, leading to increased water permeability, drainage performance and water flow-out efficiency. This facilitates deep dewatering of sludge without cell lysis. The study reveals that the G-agent primarily improves water flow-out efficiency rather than water flowability, indicating that cell lysis and bound water release are not indispensable prerequisites for sludge deep-dewatering. Furthermore, it presents an encouraging prospect for overcoming the limitations associated with conventional sludge deep-dewatering processes.

3.
Front Pediatr ; 12: 1308931, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38720947

RESUMEN

Background: Idiopathic scoliosis significantly affects the physical and mental health of children and adolescents, with varying prevalence rates in different regions. The occurrence of idiopathic scoliosis is associated with genetic regulation and biochemical factors, but the changes in exosome-derived miRNA profiles among idiopathic scoliosis patients remain unclear. This study aimed to determine the prevalence of idiopathic scoliosis in Yunnan Province, China, and identify key exosome-derived miRNAs in idiopathic scoliosis through a cohort study. Methods: From January 2018 to December 2020, a cross-sectional study on idiopathic scoliosis in children and adolescents was conducted in Yunnan Province. A total of 84,460 students from 13 cities and counties in Yunnan Province participated in a scoliosis screening program, with ages ranging from 7 to 19 years. After confirmation through screening and imaging results, patients with severe idiopathic scoliosis and normal control individuals were selected using propensity matching. Subsequently, plasma exosome-derived miRNA sequencing and RT-qPCR validation were performed separately. Based on the validation results, diagnostic performance analysis and target gene prediction were conducted for differential plasma exosome-derived miRNAs. Results: The overall prevalence of idiopathic scoliosis in children and adolescents in Yunnan Province was 1.10%, with a prevalence of 0.87% in males and 1.32% in females. The peak prevalence was observed at age 13. Among patients diagnosed with idiopathic scoliosis, approximately 12.8% had severe cases, and there were more cases of double curvature than of single curvature, with thoracolumbar curvature being the most common in the single-curvature group. Sequencing of plasma exosome-derived miRNAs associated with idiopathic scoliosis revealed 56 upregulated and 153 downregulated miRNAs. Further validation analysis confirmed that hsa-miR-27a-5p, hsa-miR-539-5p, and hsa-miR-1246 have potential diagnostic value. Conclusions: We gained insights into the epidemiological characteristics of idiopathic scoliosis in Yunnan Province and conducted further analysis of plasma exosome-derived miRNA changes in patients with severe idiopathic scoliosis. This study has provided new insights for the prevention and diagnosis of idiopathic scoliosis, paving the way for exploring clinical biomarkers and molecular regulatory mechanisms. However, further validation and elucidation of the detailed biological mechanisms underlying these findings will be required in the future.

4.
Artículo en Inglés | MEDLINE | ID: mdl-38717586

RESUMEN

Carbon material has widely been utilized in the synthesis of efficient carbon-supported Pt (Pt/C) catalysts, in which the structural properties greatly influence the electrocatalytic performances of Pt/C catalysts. However, the effects of intrinsic defects in carbon supports on the performance of the alkaline hydrogen evolution reaction (HER) have not been systematically investigated. Herein, porous carbon supports with different degrees of intrinsic defects were prepared by a simple template-assisted strategy, and the resulting samples were systematically studied by various analytical methods. The results suggested that the presence of abundant intrinsic defects (vacancy and topological defects) in the carbon support was advantageous in terms of favoring the dispersion and anchoring of Pt species, promoting electron transfer between Pt atoms and the carbon support, and tuning the electronic states of Pt species. These features improved the HER performance of Pt/C catalysts. Compared to the nontemplate-assisted carbon-supported Pt catalyst (Pt/NTC) with an overpotential of 178 mV, the optimized template-assisted carbon-supported Pt catalyst (Pt/TC) exhibited a lower overpotential of 58 mV at 10 mA cm-2. Besides, the Pt/TC catalyst displayed better HER durability than the Pt/NTC catalyst owing to its strong metal-support interaction. The DFT calculations confirmed the important role played by intrinsic defects (vacancy and topological defects) in stabilizing Pt atoms, with Pt-C3 coordination identified as the most favorable structure for improving the HER performance of Pt. Overall, novel insights on the significant contribution of intrinsic defects in porous carbon supports on the HER performances of Pt/C catalysts were provided, useful for future design and fabrication of advanced carbon-supported catalysts or other carbon-based electrode materials.

5.
Front Endocrinol (Lausanne) ; 15: 1340608, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38699385

RESUMEN

Objectives: This study aims to investigate the causal relationship between Alzheimer's Disease (AD) and Diabetic Retinopathy (DR). Methods: Employing Mendelian Randomization (MR), Generalized Summary-data-based Mendelian Randomization (GSMR), and the MR-Steiger test, this study scrutinizes the genetic underpinnings of the hypothesized causal association between AD and DR, as well as its Proliferative DR (PDR) and Non-Proliferative DR (NPDR) subtypes. Comprehensive data from Genome-Wide Association Studies (GWAS) were analyzed, specifically AD data from the Psychiatric Genomics Consortium (71,880 cases/383,378 controls), and DR, PDR, and NPDR data from both the FinnGen consortium (FinnGen release R8, DR: 5,988 cases/314,042 controls; PDR: 8,383 cases/329,756 controls; NPDR: 3,446 cases/314,042 controls) and the IEU OpenGWAS (DR: 14,584 cases/176,010 controls; PDR: 8,681 cases/204,208 controls; NPDR: 2,026 cases/204,208 controls). The study also incorporated Functional Mapping and Annotation (FUMA) for an in-depth analysis of the GWAS results. Results: The MR analyses revealed that genetic susceptibility to AD significantly increases the risk of DR, as evidenced by GWAS data from the FinnGen consortium (OR: 2.5090; 95% confidence interval (CI):1.2102-5.2018, false discovery rate P-value (PFDR)=0.0201; GSMR: bxy=0.8936, bxy_se=0.3759, P=0.0174), NPDR (OR: 2.7455; 95% CI: 1.3178-5.7197, PFDR=0.0166; GSMR: bxy=0.9682, bxy_se=0.3802, P=0.0126), and PDR (OR: 2.3098; 95% CI: 1.2411-4.2986, PFDR=0.0164; GSMR: bxy=0.7962, bxy_se=0.3205, P=0.0129) using DR GWAS from FinnGen consortium. These results were corroborated by DR GWAS datasets from IEU OpenGWAS. The MR-Steiger test confirmed a significant association of all identified instrumental variables (IVs) with AD. While a potential causal effect of DR and its subtypes on AD was identified, the robustness of these results was constrained by a low power value. FUMA analysis identified OARD1, NFYA, TREM1 as shared risk genes between DR and AD, suggesting a potential genetic overlap between these complex diseases. Discussion: This study underscores the contribution of AD to an increased risk of DR, as well as NPDR and PDR subtypes, underscoring the necessity of a holistic approach in the management of patients affected by these conditions.


Asunto(s)
Enfermedad de Alzheimer , Retinopatía Diabética , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Humanos , Enfermedad de Alzheimer/genética , Factores de Riesgo , Retinopatía Diabética/genética , Retinopatía Diabética/epidemiología , Retinopatía Diabética/etiología , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple
6.
Mol Biol Rep ; 51(1): 538, 2024 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-38642209

RESUMEN

The nuclear factor-κB (NF-κB) family, consisting of several transcription factors, has been implicated in the regulation of cell proliferation and invasion, as well as inflammatory reactions and tumor development. Cervical cancer (CC) results from long-term interactions of multiple factors, among which persistent high-risk human papillomavirus (hrHPV) infection is necessary. During different stages from early to late after HPV infection, the activity of NF-κB varies and plays various roles in carcinogenesis and progress of CC. As the center of the cell signaling transduction network, NF-κB can be activated through classical and non-classical pathways, and regulate the expression of downstream target genes involved in regulating the tumor microenvironment and acquiring hallmark traits of CC cells. Targeting NF-κB may help treat CC and overcome the resistance to radiation and chemotherapy. Even though NF-κB inhibitors have not been applied in clinical treatment as yet, due to limitations such as dose-restrictive toxicity and poor tumor-specificity, it is still considered to have significant therapeutic potential and application prospects. In this review, we focus on the role of NF-κB in the process of CC occurrence and hallmark capabilities acquisition. Finally, we summarize relevant NF-κB-targeted treatments, providing ideas for the prevention and treatment of CC.


Asunto(s)
FN-kappa B , Neoplasias del Cuello Uterino , Femenino , Humanos , Carcinogénesis/genética , Carcinogénesis/metabolismo , Inflamación , FN-kappa B/genética , FN-kappa B/metabolismo , Factores de Transcripción , Microambiente Tumoral , Neoplasias del Cuello Uterino/metabolismo
7.
Front Immunol ; 15: 1368099, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38665923

RESUMEN

Early increase in the level of endothelial progenitor cells (EPCs) in the systemic circulation occurs in patients with septic infection/sepsis. The significance and underlying mechanisms of this response remain unclear. This study investigated the bone marrow EPC response in adult mice with septic infection induced by intravenous injection (i.v.) of Escherichia coli. For in vitro experiments, sorted marrow stem/progenitor cells (SPCs) including lineage(lin)-stem cell factor receptor (c-kit)+stem cell antigen-1 (Sca-1)-, lin-c-kit+, and lin- cells were cultured with or without lipopolysaccharides (LPSs) and recombinant murine vascular endothelial growth factor (VEGF) in the absence and presence of anti-Sca-1 crosslinking antibodies. In a separate set of experiments, marrow lin-c-kit+ cells from green fluorescence protein (GFP)+ mice, i.v. challenged with heat-inactivated E. coli or saline for 24 h, were subcutaneously implanted in Matrigel plugs for 5 weeks. Marrow lin-c-kit+ cells from Sca-1 knockout (KO) mice challenged with heat-inactivated E. coli for 24 h were cultured in the Matrigel medium for 8 weeks. The marrow pool of EPCs bearing the lin-c-kit+Sca-1+VEGF receptor 2 (VEGFR2)+ (LKS VEGFR2+) and LKS CD133+VEGFR2+ surface markers expanded rapidly following septic infection, which was supported by both proliferative activation and phenotypic conversion of marrow stem/progenitor cells. Increase in marrow EPCs and their reprogramming for enhancing angiogenic activity correlated with cell-marked upregulation of Sca-1 expression. Sca-1 was coupled with Ras-related C3 botulinum toxin substrate 2 (Rac2) in signaling the marrow EPC response. Septic infection caused a substantial increase in plasma levels of IFN-γ, VEGF, G-CSF, and SDF-1. The early increase in circulating EPCs was accompanied by their active homing and incorporation into pulmonary microvasculature. These results demonstrate that the marrow EPC response is a critical component of the host defense system. Sca-1 signaling plays a pivotal role in the regulation of EPC response in mice with septic infection.


Asunto(s)
Células Progenitoras Endoteliales , Proteínas de la Membrana , Sepsis , Animales , Células Progenitoras Endoteliales/metabolismo , Células Progenitoras Endoteliales/inmunología , Sepsis/inmunología , Sepsis/metabolismo , Ratones , Ratones Noqueados , Escherichia coli/inmunología , Infecciones por Escherichia coli/inmunología , Ratones Endogámicos C57BL , Factor A de Crecimiento Endotelial Vascular/metabolismo , Antígenos Ly/metabolismo , Células de la Médula Ósea/metabolismo , Células de la Médula Ósea/inmunología , Células Cultivadas , Masculino
8.
Front Neurosci ; 18: 1380171, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38650618

RESUMEN

Periaqueductal gray (PAG), an integration center for neuronal signals, is located in the midbrain and regulates multiple physiological and pathological behaviors, including pain, defensive and aggressive behaviors, anxiety and depression, cardiovascular response, respiration, and sleep-wake behaviors. Due to the different neuroanatomical connections and functional characteristics of the four functional columns of PAG, different subregions of PAG synergistically regulate various instinctual behaviors. In the current review, we summarized the role and possible neurobiological mechanism of different subregions of PAG in the regulation of pain, defensive and aggressive behaviors, anxiety, and depression from the perspective of the up-down neuronal circuits of PAG. Furthermore, we proposed the potential clinical applications of PAG. Knowledge of these aspects will give us a better understanding of the key role of PAG in physiological and pathological behaviors and provide directions for future clinical treatments.

9.
Injury ; 55(6): 111578, 2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38669891

RESUMEN

OBJECTIVE: To analyze the main influencing factors of ASD (Acute Stress Disorder) in inpatients, and provide some evidence for early clinical identification and intervention of ASD. METHODS: In this study, 489 inpatients were selected from 3 general hospitals in Zunyi City from September 2020 to August 2021. The patients were followed up with questionnaires. Mann Whitney U test, Logistic Regression analysis and Generalized Estimation Equation were used for difference comparison and influencing factor analyses. RESULTS: Multivariate logistic regression showed that trauma exposure, psychological burden, fear and pain degree were risk factors of ASD in all inpatients. The sensitivity and specificity of combined using of "trauma, psychological burden, fear and pain" in predicting ASD reached 89.40 % and 79.20 %, respectively; and the area under ROC could reach 0.897. CONCLUSION: Based on the different risk factors, an early effective model could be built for ASD prediction in both traumatic and nontraumatic patients.

10.
Artículo en Inglés | MEDLINE | ID: mdl-38671166

RESUMEN

Patients with COVID-19 develop an increased risk of thromboembolism. Thromboprophylaxis is recommended for hospitalized COVID-19 patients, but the role of thromboprophylaxis in outpatients with COVID-19 is less well defined. We conducted a systematic review and meta-analysis to evaluate the safety and efficacy of thromboprophylaxis among outpatients with COVID-19. We searched PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus from inception to August 2023. The outcomes of interest were venous thromboembolic events including deep venous thrombosis and pulmonary embolism, all-cause mortality, cardiovascular events, hospitalization, major bleeding events, and non-major bleeding events. We included 6 trials comprising 3352 patients. Patients who received thromboprophylaxis had an approximately 70% reduction in venous thromboembolism (RR, 0.28 [95% CI, 0.08 to 0.93]) compared to patients who did not receive thromboprophylaxis. The risk of mortality (RR, 0.79 [95% CI, 0.35 to 1.77]), cardiovascular events (RR, 0.91 [95% CI, 0.30 to 2.73]), and hospitalization (RR, 1.09 [95% CI, 0.81 to 1.47]) were similar between the two groups. Patients who received thromboprophylaxis had a higher risk of non-major bleeding (RR, 3.48 [95% CI, 1.72 to 7.05) compared to patients who did not receive thromboprophylaxis. Thromboprophylaxis reduced the risk of venous thromboembolism but not mortality, cardiovascular events, or hospitalization among outpatients with COVID-19.

11.
Artículo en Inglés | MEDLINE | ID: mdl-38626355

RESUMEN

RATIONALE: Bronchiectasis is a pathological dilatation of the bronchi in the respiratory airways associated with environmental or genetic causes (e.g., cystic fibrosis, primary ciliary dyskinesia and primary immunodeficiency disorders), but most cases remain idiopathic. OBJECTIVES: To identify novel genetic defects in unsolved cases of bronchiectasis presenting with severe rhinosinusitis, nasal polyposis, and pulmonary Pseudomonas aeruginosa infection. METHODS: DNA was analyzed by next-generation or targeted Sanger sequencing. RNA was analyzed by quantitative PCR and single-cell RNA sequencing. Patient-derived, cells, cell cultures and secretions (mucus, saliva, seminal fluid) were analyzed by Western blotting and immunofluorescence microscopy, and mucociliary activity was measured. Blood serum was analyzed by electrochemiluminescence immunoassay. Protein structure and proteomic analyses were used to assess the impact of a disease-causing founder variant. MEASUREMENTS AND MAIN RESULTS: We identified bi-allelic pathogenic variants in WFDC2 in 11 individuals from 10 unrelated families originating from the United States, Europe, Asia, and Africa. Expression of WFDC2 was detected predominantly in secretory cells of control airway epithelium and also in submucosal glands. We demonstrate that WFDC2 is below the limit of detection in blood serum and hardly detectable in samples of saliva, seminal fluid, and airway surface liquid from WFDC2-deficient individuals. Computer simulations and deglycosylation assays indicate that the disease-causing founder variant p.Cys49Arg structurally hampers glycosylation and thus secretion of mature WFDC2. CONCLUSIONS: WFDC2 dysfunction defines a novel molecular etiology of bronchiectasis characterized by the deficiency of a secreted component of the airways. A commercially available blood test combined with genetic testing allows its diagnosis. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).

12.
Int J Pediatr Otorhinolaryngol ; 179: 111903, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38574649

RESUMEN

OBJECTIVE: To assess the effectiveness and safety of ear moulds for congenital auricle deformities. METHODS: Databases including Medline, EMBASE, Cochrane Library, Chinese BioMedical Literature Database (CBM) and Web of Science were systematically reviewed. Randomised controlled trials (RCT), non-randomised control trials (non-RCT), quasi-randomised control trials (quasi-RCT) and self-controlled before-after trials were also included. Data extraction was independently conducted by two authors. The Risk Of Bias In Non-randomised Studies of Interventions (ROBIN-I) was used to evaluate the risk bias. Heterogeneity was assessed using I2 and chi-square tests. Effective rate, adverse reaction rate and their 95%CI were calculated. Funnel plots, Begg's test as well as sensitivity and subgroup analyses were performed. RESULTS: The analysis encompassed ten studies, comprising one RCT and nine self-controlled before-after trials, involving 1860 ears (1248 children). The pooled effective rate and adverse reaction rate of ear mould were 91% (95% CI: 0.87-0.94) and 9% (95%CI: 0.02-0.17), respectively. No serious adverse reactions were reported. The effective rate of ear mould intervention showed no significant difference between age at correction≤42 days group (90%, 95%CI: 0.85-0.94) and that >42 days group (93%, 95%CI: 0.83-0.99). Similarly, there was no statistical difference in the correction efficiency between duration of wearing ear mould≤30 days group (90%, 95%CI: 0.85-0.94) and that >30 days group (92%, 95%CI: 0.86-0.96). The effective rate for correcting cryptotia ear (98%, P < 0.001), cup ear (93%, P = 0.004) and prominent ear (90%, P = 0.014) was higher than that of helical rim deformity (66%). CONCLUSIONS: In the short term, the use of ear moulds is effective and safe in correcting congenital auricle deformities. Notably, the correction efficacy for cryptotia, cup ear and prominent ear deformities surpasses that of helical rim deformities. However, further research is required to ascertain the impact of the duration of wearing on the correction of congenital auricle deformities.

13.
Front Nutr ; 11: 1343394, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38571750

RESUMEN

In this work, the effect of the addition of γ-polyglutamic acid (γ-PGA) on the rheology, physicochemical properties, and microstructure of fish gelatin (FG) emulsion gel was investigated. Samples of the emulsion gel were evaluated for rheological behavior and stability prior to gelation. The mechanical properties and water-holding capacity (WHC) of the emulsion were determined after gelation. The microstructure of the emulsion gel was further examined using confocal laser scanning microscopy (CLSM). The results indicated a gradual increase in the apparent viscosity and gelation temperature of the emulsion at a higher concentration of γ-PGA. Additionally, frequency scan results revealed that on the addition of γ-PGA, FG emulsion exhibited a stronger structure. The emulsion containing 0.1% γ-PGA exhibited higher stability than that of the control samples. The WHC and gel strength of the emulsion gel increased on increasing the γ-PGA concentration. CLSM images showed that the addition of γ-PGA modified the structure of the emulsion gel, and the droplets containing 0.1% γ-PGA were evenly distributed. Moreover, γ-PGA could regulate the droplet size of the FG emulsion and its size distribution. These findings suggest that the viscoelasticity and structure of FG emulsion gels could be regulated by adjusting the γ-PGA concentration. The γ-PGA-modified FG emulsion gel also exhibited improved rheology and physicochemical properties. The results showed that γ-PGA-modified FG emulsion gel may find potential applications in food, medicine, cosmetics, and other industries.

15.
Intern Med J ; 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38563467

RESUMEN

BACKGROUND AND AIMS: Sleep-disordered breathing (SDB) and nocturnal hypoxemia were known to be present in patients with chronic thromboembolic pulmonary hypertension (CTEPH), but the difference between SDB and nocturnal hypoxemia in patients who have chronic thromboembolic pulmonary disease (CTEPD) with or without pulmonary hypertension (PH) at rest remains unknown. METHODS: Patients who had CTEPH (n = 80) or CTEPD without PH (n = 40) and who had undergone sleep studies from July 2020 to October 2022 at Shanghai Pulmonary Hospital were enrolled. Nocturnal mean SpO2 (Mean SpO2) <90% was defined as nocturnal hypoxemia, and the percentage of time with a saturation below 90% (T90%) exceeding 10% was used to evaluate the severity of nocturnal hypoxemia. Logistic and linear regression analyses were performed to investigate the difference and potential predictor of SDB or nocturnal hypoxemia between CTEPH and CTEPD without PH. RESULTS: SDB was similarly prevalent in CTEPH and CTEPD without PH (P = 0.104), both characterised by obstructive sleep apnoea (OSA). Twenty-two patients with CTEPH were diagnosed with nocturnal hypoxemia, whereas only three were diagnosed with CTEPD without PH (P = 0.021). T90% was positively associated with mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance in patients with CTEPH and CTEPD without PH (P < 0.001); T90% was also negatively related to cardiac output in these patients. Single-breath carbon monoxide diffusing capacity, sex and mPAP were all correlated with nocturnal hypoxemia in CTEPH and CTEPD without PH (all P < 0.05). CONCLUSION: Nocturnal hypoxemia was worse in CTEPD with PH; T90%, but not SDB, was independently correlated with the hemodynamics in CTEPD with or without PH.

16.
Nat Commun ; 15(1): 3661, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38688901

RESUMEN

Optochemistry, an emerging pharmacologic approach in which light is used to selectively activate or deactivate molecules, has the potential to alleviate symptoms, cure diseases, and improve quality of life while preventing uncontrolled drug effects. The development of in-vivo applications for optochemistry to render brain cells photoresponsive without relying on genetic engineering has been progressing slowly. The nucleus accumbens (NAc) is a region for the regulation of slow-wave sleep (SWS) through the integration of motivational stimuli. Adenosine emerges as a promising candidate molecule for activating indirect pathway neurons of the NAc expressing adenosine A2A receptors (A2ARs) to induce SWS. Here, we developed a brain-permeable positive allosteric modulator of A2ARs (A2AR PAM) that can be rapidly photoactivated with visible light (λ > 400 nm) and used it optoallosterically to induce SWS in the NAc of freely behaving male mice by increasing the activity of extracellular adenosine derived from astrocytic and neuronal activity.


Asunto(s)
Adenosina , Núcleo Accumbens , Receptor de Adenosina A2A , Sueño de Onda Lenta , Animales , Núcleo Accumbens/metabolismo , Núcleo Accumbens/efectos de los fármacos , Núcleo Accumbens/fisiología , Masculino , Receptor de Adenosina A2A/metabolismo , Receptor de Adenosina A2A/genética , Ratones , Adenosina/metabolismo , Adenosina/farmacología , Regulación Alostérica , Sueño de Onda Lenta/fisiología , Sueño de Onda Lenta/efectos de los fármacos , Astrocitos/metabolismo , Astrocitos/efectos de los fármacos , Luz , Neuronas/metabolismo , Neuronas/efectos de los fármacos , Ratones Endogámicos C57BL , Humanos , Agonistas del Receptor de Adenosina A2/farmacología
17.
J Am Heart Assoc ; 13(6): e031867, 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38497483

RESUMEN

BACKGROUND: Circular RNAs can serve as regulators influencing the development of pulmonary hypertension (PH). However, their function in pulmonary vascular intimal injury remains undefined. Thus, we aimed to identify specifically expressed circular RNAs in pulmonary microvascular endothelial cells (PMECs) under hypoxia and PH. METHODS AND RESULTS: Deep RNA sequencing and quantitative real-time polymerase chain reaction revealed that circALMS1 (circular RNA Alstrom syndrome protein 1) was reduced in human PMECs under hypoxia (P<0.0001). Molecular biology and histopathology experiments were used to elucidate the roles of circALMS1 in regulating PMEC dysfunction among patients with PH. The circALMS1 expression was decreased in the plasma of patients with PH (P=0.0315). Patients with lower circALMS1 levels had higher risk of death (P=0.0006). Moreover, the circALMS1 overexpression of adeno-associated viruses improved right ventricular function and reduced pulmonary vascular remodeling in monocrotaline-PH and sugen/hypoxia-PH rats (P<0.05). Furthermore, circALMS1 overexpression promoted apoptosis and inhibited PMEC proliferation and migration under hypoxia by directly downregulating miR-17-3p (P<0.05). Dual luciferase assay confirmed the direct binding of circALMS1 to miR-17-3p and miR-17-3p binding to its target gene YT521-B homology domain-containing family protein 2 (YTHDF2) (P<0.05). The YTHDF2 levels were also downregulated in hypoxic PMECs (P<0.01). The small interfering RNA YTHDF2 reversed the effects of miR-17-3p inhibitors on PMEC proliferation, migration, and apoptosis. Finally, the results indicated that, although YTHDF2, as an N(6)-methyladenosine reader protein, contributes to the degradation of many circular RNAs, it could not regulate the circALMS1 levels in PMECs (P=0.9721). CONCLUSIONS: Our study sheds new light on circALMS1-regulated dysfunction of PMECs by the miR-17-3p/YTHDF2 pathway under hypoxia and provides insights into the underlying pathogenesis of PH.


Asunto(s)
Hipertensión Pulmonar , MicroARNs , Humanos , Ratas , Animales , Hipertensión Pulmonar/metabolismo , MicroARNs/metabolismo , Células Endoteliales/metabolismo , ARN Circular/genética , Arteria Pulmonar , Hipoxia/complicaciones , Proliferación Celular/fisiología
18.
Vascular ; : 17085381241240237, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38490959

RESUMEN

OBJECTIVES: The study compared the outcomes between covered-stents grafting (CSG) and ligation of femoral artery (LFA) in the treatment of infected femoral pseudoaneurysm (IFP) caused by intravenous drug injection. METHODS: From 1st January 2016 to 30th November 2021, the clinical data of patients with IFP caused by intravenous drug injection who underwent CSG (n = 31, 55.4%) and LFA (n = 25, 45.4%) are retrospectively analyzed. We compared the baseline characteristics and clinical outcomes of the two groups, including early and late mortality and morbidity. RESULTS: A total of 56 patients were enrolled in the study, comprising 50 (89.3%) men and 6 (10.7%) women, with a mean age of 34.3 years. There was no significant difference observed between the two groups in terms of 30-day mortality (3.2% vs 0%, p = .365) and length of stay (9 [7, 12] vs 11 [8.5, 12.5] days, p = .236). However, group CSG exhibited a lower rate of intermittent claudication (0% vs 32%, p = .001), less blood loss (67.1 ± 22.5 mL vs 177.0 ± 59.8 mL, p < .001), and shorter surgery duration (57.5 ± 9.9 min vs 84.4 ± 22.8 min, p < .001) compared to group LFA. The LFA group were divided into subgroups according to the ligation site. The amputation rate of superficial femoral artery ligation group (0 vs 27.3%, p = .014) was significantly lower than common femoral artery ligation. CONCLUSIONS: Covered-stents grafting may be a preferable treatment to LFA for IFP due to intravenous drug abuse, particularly when the entry tear is located in the common femoral artery.

19.
PLoS One ; 19(3): e0296811, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38512912

RESUMEN

BACKGROUND: To analyze vault effects of crystalline lens rise (CLR) and anterior chamber parameters (recorded by Pentacam) in highly myopic patients receiving implantable collamer lenses (ICLs), which may avoid subsequent complications such as glaucoma and cataract caused by the abnormal vault. METHODS: We collected clinical data of 137 patients with highly myopic vision, who were all subsequent recipients of V4c ICLs between June 2020 and January 2021. Horizontal ciliary sulcus-to-sulcus diameter (hSTS) and CLR were measured by ultrasonic biomicroscopy (UBM), and a Pentacam anterior segment analyzer was used to measure horizontal white-to-white diameter (hWTW), anterior chamber depth (ACD), anterior chamber angle (ACA), anterior chamber volume (ACV), CLR, and postoperative vault (Year 1 and Month 1). The lens thickness (LT) was determined by optical biometry (IOL Master instrument). The predictive model was generated through multiple linear regression analyses of influential factors, such as hSTS, CLR, hWTW, ACD, ACA, ACV, ICL size, and LT. The predictive performance of the multivariate model on vault after ICL was assessed using the receiver operating characteristic (ROC) curve with area under the curve (AUC) as well as the point of tangency. RESULTS: Average CLR assessed by UBM was lower than the average value obtained by Pentacam (0.561 vs. 0.683). Bland-Altman analysis showed a good consistency in the two measurement methods and substantial correlation (r = 0.316; P = 0.000). The ROC curve of Model 1 (postoperative Year 1) displayed an AUC of 0.847 (95% confidence interval [CI]: 74.19-95.27), with optimal threshold of 0.581 (sensitivity, 0.857; specificity, 0.724). In addition, respective values for Model 2 (postoperative Month 1) were 0.783 (95% CI: 64.94-91.64) and 0.522 (sensitivity, 0.917; specificity, 0.605). CONCLUSION: CLR and anterior chamber parameters are important determinants of postoperative vault after ICL placement. The multivariate regression model we constructed may serve in large part as a predictive gauge, effectively avoid postoperative complication.


Asunto(s)
Cristalino , Miopía , Lentes Intraoculares Fáquicas , Humanos , Implantación de Lentes Intraoculares/efectos adversos , Agudeza Visual , Cristalino/cirugía , Cámara Anterior/diagnóstico por imagen , Miopía/cirugía , Estudios Retrospectivos
20.
Front Pediatr ; 12: 1363419, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38500589

RESUMEN

Tracheal stenosis is a rare but life-threatening disease in preterm infants. Misdiagnosis as congenital tracheal stenosis is common, making surgical management challenging. This report presents a case of a preterm infant with tracheal stenosis and congenital heart malformation treated with ECMO-assisted tracheal resection and end-to-end anastomosis. A male infant was born at 30 weeks of gestation with severe asphyxia, cardiac insufficiency, and pneumonia. Following failed medical treatment, fiberoptic bronchoscopy confirmed mid-tracheal to carinal stenosis. After a 2-week treatment course, ECMO-assisted tracheal resection and end-to-end anastomosis were performed successfully. This case confirms the feasibility of tracheal resection and end-to-end anastomosis in low-weight, preterm infants with tracheal stenosis born at 30 weeks gestation. The utilization of ECMO for oxygenation during surgery provides a clear surgical field and shorter operating time. Surgical intervention may be necessary for neonatal tracheal stenosis depending on the clinical presentation.

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