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1.
Pediatr Nephrol ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38597974

RESUMO

BACKGROUND: Medication nonadherence is a barrier to hypertension control. The Centers for Disease Control and Prevention recommends prescribing 90-day fills for maintenance medications yet antihypertensives are often dispensed as 30-day fills. Our objectives were to examine how often patients receive 30-day supplies of medication despite prescriptions for longer duration and to examine the effect of medication fill duration on adherence and hypertension control. METHODS: We conducted a retrospective cohort study of pediatric patients with hypertension over a 3-year period. For each patient, days prescribed per fill were compared to days dispensed per fill using pharmacy reports and insurance claim data. Proportion of Days Covered (PDC) was calculated to estimate adherence. Hypertension control was determined by provider assessment of control and blood pressure measurement at the final visit. RESULTS: Final cohort included 449 patients. A total of 70% had at least one prescription for ≥ 90 days but only 37% had at least one dispense for ≥ 90 days. There was no difference in the likelihood of being prescribed a 90-day fill by insurance type (public vs. private); however, patients with public insurance were less likely to be dispensed a 90-day fill (OR = 0.068, p < 0.001). Patients who received 90-day fills had better adherence (median PDC 77.5% vs. 58.1%, p < 0.001) and were more likely to have hypertension control based on provider assessment. CONCLUSIONS: Longer fill duration is associated with improved adherence and hypertension control. Patients with public insurance are markedly less likely to be dispensed 90-day fills, a modifiable barrier to improving adherence.

2.
Front Nutr ; 11: 1270523, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38533463

RESUMO

Background: Maternal stress is pervasive in the neonatal intensive care unit (NICU). Maternal stress is associated with changes in human milk (HM) immunomodulatory agents, which may impact neonatal health. We sought to determine the association between maternal stress, HM immunoglobulin A (IgA) and cortisol, and to assess how these milk components correlate with infant immune and neurodevelopmental outcomes. We then compared how these associations persist over time. Methods: The study design involved a cohort study of exclusively breastfeeding mothers and their singleton moderately preterm (28-34 weeks) infants admitted to the NICU. We collected maternal serum, maternal saliva, and first-morning whole milk samples, and administered maternal stress questionnaires at 1 and 5 weeks postpartum. We analyzed the samples for HM IgA (using a customized immunoassay in skim milk) and for HM and salivary cortisol (using a chemiluminescent immunoassay). Infant illness was assessed using the Score for Neonatal Acute Physiology II (SNAP II) and SNAP II with Perinatal Extension (SNAPPE II), and infant neurodevelopment were assessed using the Test of Infant Motor Performance. We analyzed changes in HM IgA and cortisol over time using paired t-tests. Furthermore, we performed correlation and regression analyses after adjusting for gestational age (GA), corrected GA, and infant days of life. Results: In our study, we enrolled 26 dyads, with a mean maternal age of 28.1 years, consisting of 69% white, 19% Black, and 8% Hispanic. Cortisol: Salivary and HM cortisol were closely associated in week 1 but not in week 5. Though mean salivary cortisol remained stable over time [2.41 ng/mL (SD 2.43) to 2.32 (SD 1.77), p = 0.17], mean HM cortisol increased [1.96 ng/mL (SD 1.93) to 5.93 ng/mL (SD 3.83), p < 0.001]. Stress measures were inversely associated with HM cortisol at week 1 but not at week 5. IgA: HM IgA decreased over time (mean = -0.14 mg/mL, SD 0.53, p < 0.0001). High maternal stress, as measured by the Parental Stressor Scale: neonatal intensive care unit (PSS:NICU), was positively associated with HM IgA at week 5 (r = 0.79, P ≤ 0.001). Higher IgA was associated with a lower (better) SNAP II score at week 1 (r = -0.74, p = 0.05). No associations were found between maternal stress, salivary cortisol, HM cortisol, or HM IgA and neurodevelopment at discharge (as assessed using the TIMP score). Furthermore, these relationships did not differ by infant sex. Conclusion: Maternal stress showed associations with HM cortisol and HM IgA. In turn, HM IgA was associated with lower measures of infant illness.

3.
Front Pharmacol ; 15: 1367682, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38500766

RESUMO

Background: In traditional Mongolian or Tibetan medicine in China, Chebulae Fructus (CF) is widely used to process or combine with aconitums to decrease the severe toxicity of aconitums. Researches in this area have predominantly focused on tannins, with few research on other major CF components for cardiotoxicity mitigation. The present study aimed to clarify whether triterpenoids can attenuate the cardiotoxicity caused by mesaconitine (MA) and investigate the mechanism of cardiotoxicity attenuation. Methods: Firstly, the pharmacophore model, molecular docking, and 3D-QSAR model were used to explore the mechanism of CF components in reducing the toxicity of MA mediated by the TRPV1 channel. Then three triterpenoids were selected to verify whether the triterpenoids had the effect of lowering the cardiotoxicity of MA using H9c2 cells combined with MTT, Hoechst 33258, and JC-1. Finally, Western blot, Fluo-3AM, and MTT assays combined with capsazepine were used to verify whether the triterpenoids reduced H9c2 cardiomyocyte toxicity induced by MA was related to the TRPV1 channel. Results: Seven triterpenoids in CF have the potential to activate the TRPV1 channel. And they exhibited greater affinity for TRPV1 compared to other compounds and MA. However, their activity was relatively lower than that of MA. Cell experiments revealed that MA significantly reduced H9c2 cell viability, resulting in diminished mitochondrial membrane potential and nuclear pyknosis and damage. In contrast, the triterpenoids could improve the survival rate significantly and counteract the damage of MA to the cells. We found that MA, arjungenin (AR), and maslinic acid (MSA) except corosolic acid (CRA) upregulated the expression of TRPV1 protein. MA induced a significant influx of calcium, whereas all three triterpenoids alleviated this trend. Blocking the TRPV1 channel with capsazepine only increased the cell viability that had been simultaneously treated with MA, and AR, or MSA. However, there was no significant difference in the CRA groups treated with or without capsazepine. Conclusion: The triterpenoids in CF can reduce the cardiotoxicity caused by MA. The MSA and AR function as TRPV1 agonists with comparatively reduced activity but a greater capacity to bind to TRPV1 receptors, thus antagonizing the excessive activation of TRPV1 by MA.

4.
Small ; : e2312010, 2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38368271

RESUMO

The dispersion stability of nano-lubricating additives is crucial for the shelf life of lubricant and its practical applications. Nitrogen-sulfur co-doped carbon dots (N,S@CDs) via a one-step hydrothermal method with nitropyrene and thiourea as raw materials are hereby presented. The N and S elements are selectively distributed throughout the entire carbon skeleton with a doping amount of 22.6 at%. The as-synthesized N,S@CDs exhibit excellent dispersion stability in PEG200 and maintain stability for over one year. The experiment results indicate that N,S@CDs significantly improve the anti-wear and friction reduction properties of PEG200, while the friction coefficient is reduced from 0.25 to 0.09 with 1.5 wt% N,S@CDs addition, and the wear volume, depth, and width are reduced by 68%, 52%, and 57%, respectively. The good lubrication performance is attributed to N,S@CDs excellent dispersion stability, enhanced filling and polishing effects, and complex tribochemical reactions caused by heteroatom doping to form a stable protective film on the worn surface. Furthermore, the as-prepared N,S@CDs exhibit intrinsic fluorescence intensity in PEG200 with the photoluminescence quantum yield (PLQY) of 12.5% and remain fluorescent stable during the long-term friction process, therefore the N,S@CDs have a potential application prospect in non-destructive detection of oil leakage via fluorescence labeling method.

5.
Acta Pharmacol Sin ; 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38409216

RESUMO

Alzheimer's disease (AD), a progressive neurodegenerative disorder, is the most common cause of dementia in elderly people and substantially affects patient quality of life. Oxidative stress is considered a key factor in the development of AD. Nrf2 plays a vital role in maintaining redox homeostasis and regulating neuroinflammatory responses in AD. Previous studies show that potassium 2-(1-hydroxypentyl)-benzoate (PHPB) exerts neuroprotective effects against cognitive impairment in a variety of dementia animal models such as APP/PS1 transgenic mice. In this study we investigated whether PHPB ameriorated the progression of AD by reducing oxidative stress (OS) damage. Both 5- and 13-month-old APP/PS1 mice were administered PHPB (100 mg·kg-1·d-1, i.g.) for 10 weeks. After the cognition assessment, the mice were euthanized, and the left hemisphere of the brain was harvested for analyses. We showed that 5-month-old APP/PS1 mice already exhibited impaired performance in the step-down test, and knockdown of Nrf2 gene only slightly increased the impairment, while knockdown of Nrf2 gene in 13-month-old APP/PS1 mice resulted in greatly worse performance. PHPB administration significantly ameliorated the cognition impairments and enhanced antioxidative capacity in APP/PS1 mice. In addition, PHPB administration significantly increased the p-AKT/AKT and p-GSK3ß/GSK3ß ratios and the expression levels of Nrf2, HO-1 and NQO-1 in APP/PS1 mice, but these changes were abolished by knockdown of Nrf2 gene. In SK-N-SH APPwt cells and primary mouse neurons, PHPB (10 µM) significantly increased the p-AKT/AKT and p-GSK3ß/GSK3ß ratios and the level of Nrf2, which were blocked by knockdown of Nrf2 gene. In summary, this study demonstrates that PHPB exerts a protective effect via the Akt/GSK3ß/Nrf2 pathway and it might be a promising neuroprotective agent for the treatment of AD.

6.
Am J Audiol ; : 1-9, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38346147

RESUMO

PURPOSE: Uncorrected hearing loss can result in detrimental sequelae. Research addressing clinical presentation and genetic testing would inform clinical decision making. METHOD: A retrospective chart review of 96 patients aged 1 month to 46 years (median age = 6 years) diagnosed with hearing loss or deafness and who underwent genetic testing at University of Rochester Medical Center from 2011 to 2021. Chi-square and Fisher's exact tests examined the relationship between a diagnostic positive genetic test result and various characteristics of hearing loss, including congenital (n = 52), noncongenital (n = 34), prelingual (n = 53), postlingual (n = 33), progressive (n = 13), not progressive (n = 47), bilateral (n = 67), unilateral (n = 26), sensorineural (n = 68), conductive (n = 14), mixed (n = 5), syndromic (n = 10), and nonsyndromic (n = 87) hearing loss. We also examined the number of patients with presence of developmental disabilities (n = 35), having a first-degree relative with hearing loss (n = 19), having hearing aids or cochlear implants (n = 45), and having a multisystem presentation prior to diagnosis (n = 45). RESULTS: Patients with sensorineural hearing loss (44.1%) had significantly more diagnostic positive results than those with mixed (0%) or conductive hearing loss (21.4%), p = .004. However, significantly fewer patients with disabilities (19.4%) had diagnostic positive tests than those without disabilities (43.3%), p < .05. More patients with a multisystem presentation were also found to have syndromic causes of hearing loss (23.3%) than patients who did not have a multisystem presentation, p < .05. CONCLUSIONS: Our study suggests a significant association between sensorineural type of hearing loss and a diagnostic positive genetic test result, while the presence of disabilities was significantly associated with a nondiagnostic genetic test result. Knowledge of these findings is critical for understanding the cause of the hearing loss, identifying other associated symptoms, and determining risk to family members.

7.
ACS Macro Lett ; : 260-265, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38335274

RESUMO

The development of codelivery approaches for combination therapy is of great significance, especially for natural products that need to be combined to achieve therapeutic effects. Targeted delivery of multiple drugs through a single carrier remains a challenge. Here, a multi-drug-loaded hydrogel, incorporating quercetin, demethyleneberberine, and dencichine, based on a G4-quadruplex was designed and prepared. Catechol drugs were responsively released in a simulated inflammatory pathological environment by a borate ester linkage, while coagulating dencichine encapsulated in the hydrogel was released along with the degradation of assemblies. The multi-drug-loaded codelivery system is expected to enhance the treatment of inflammatory bowel disease through the synergistic effect of the components. The preparation, characteristic, and physicochemical properties of the multi-drug-loaded assembly were depicted by NMR, CD, and TEM. Degradation assays in vitro proved the good biocompatibility and safety of the hydrogel and a potential pathway to injectable administration. The assays of typical inflammatory cytokines, including TNF-α and IL-6, indicated that these can be significantly suppressed by the treatment of the hydrogel. The current work provided a simple strategy to construct a multi-drug-loaded hydrogel carrier, which facilitated synergistic therapy for natural products by a codelivery approach.

8.
Micromachines (Basel) ; 15(1)2024 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-38276855

RESUMO

This work presents highly responsive gate-controlled p-GaN/AlGaN/GaN ultraviolet photodetectors (UVPDs) on Si substrates with a high-transmittance ITO gate. The two-dimensional electron gas (2DEG) in the quantum well of the polarized AlGaN/GaN heterojunction was efficiently depleted by the p-GaN gate, leading to a high photo-to-dark current ratio (PDCR) of 3.2 × 105. The quantum wells of the p-GaN/AlGaN and AlGaN/GaN heterojunctions can trap the holes and electrons excited by the UV illumination, thus efficiently triggering a photovoltaic effect and photoconductive effect, separately. Furthermore, the prepared photodetectors allow flexible adjustment of the static bias point, making it adaptable to different environments. Compared to traditional thin-film semi-transparent Ni/Au gates, indium tin oxide (ITO) exhibits higher transmittance. Under 355 nm illumination, the photodetector exhibited a super-high responsivity exceeding 3.5 × 104 A/W, and it could even exceed 106 A/W under 300 nm illumination. The well-designed UVPD combines both the advantages of the high-transmittance ITO gate and the structure of the commercialized p-GaN/AlGaN/GaN high-electron-mobility transistors (HEMTs), which opens a new possibility of fabricating large-scale, low-cost, and high-performance UVPDs in the future.

9.
Chem Rev ; 124(1): 164-209, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38044580

RESUMO

The performance of a chemical reaction is critically dependent on the electronic and/or geometric structures of a material in heterogeneous catalysis. Over the past century, the Sabatier principle has already provided a conceptual framework for optimal catalyst design by adjusting the electronic structure of the catalytic material via a change in composition. Beyond composition, it is essential to recognize that the geometric atomic structures of a catalyst, encompassing terraces, edges, steps, kinks, and corners, have a substantial impact on the activity and selectivity of a chemical reaction. Crystal-phase engineering has the capacity to bring about substantial alterations in the electronic and geometric configurations of a catalyst, enabling control over coordination numbers, morphological features, and the arrangement of surface atoms. Modulating the crystallographic phase is therefore an important strategy for improving the stability, activity, and selectivity of catalytic materials. Nonetheless, a complete understanding of how the performance depends on the crystal phase of a catalyst remains elusive, primarily due to the absence of a molecular-level view of active sites across various crystal phases. In this review, we primarily focus on assessing the dependence of catalytic performance on crystal phases to elucidate the challenges and complexities inherent in heterogeneous catalysis, ultimately aiming for improved catalyst design.

10.
J Cell Mol Med ; 28(1): e18041, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37987202

RESUMO

Diffuse large B-cell lymphoma (DLBCL) is difficult to treat due to the high recurrence rate and therapy intolerance, so finding potential therapeutic targets for DLBCL is critical. FK506-binding protein 3 (FKBP3) contributes to the progression of various cancers and is highly expressed in DLBCL, but the role of FKBP3 in DLBCL and its mechanism are not clear. Our study demonstrated that FKBP3 aggravated the proliferation and stemness of DLBCL cells, and tumour growth in a xenograft mouse model. The interaction between FKBP3 and parkinsonism associated deglycase (PARK7) in DB cells was found using co-immunoprecipitation assay. Knockdown of FKBP3 enhanced the degradation of PARK7 through increasing its ubiquitination modification. Forkhead Box O3 (FOXO3) belongs to the forkhead family of transcription factors and inhibits DLBCL, but the underlying mechanism has not been reported. We found that FOXO3 bound the promoter of FKBP3 and then suppressed its transcription, eventually weakening DLBCL. Mechanically, FKBP3 activated Wnt/ß-catenin signalling pathway mediated by PARK7. Together, FKBP3 increased PARK7 and then facilitated the malignant phenotype of DLBCL through activating Wnt/ß-catenin pathway. These results indicated that FKBP3 might be a potential therapeutic target for the treatment of DLBCL.


Assuntos
Linfoma Difuso de Grandes Células B , beta Catenina , Humanos , Camundongos , Animais , beta Catenina/metabolismo , Proteína Desglicase DJ-1/genética , Regulação Neoplásica da Expressão Gênica , Via de Sinalização Wnt/genética , Fenótipo , Linfoma Difuso de Grandes Células B/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Proteínas de Ligação a Tacrolimo/metabolismo
11.
Eur J Pharm Sci ; 192: 106625, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37918545

RESUMO

Saccharides are a popular group of stabilizers in liquid, frozen and freeze dried protein formulations. The current work reviewed the stabilization mechanisms of three groups of saccharides: (i) Disaccharides, specifically sucrose and trehalose; (ii) cyclodextrins (CDs), a class of cyclic oligosaccharides; and (iii) dextrans, a class of polysaccharides. Compared to sucrose, trehalose exhibits a more pronounced preferential exclusion effect in liquid protein formulations, due to its stronger interaction with water molecules. However, trehalose obtains higher phase separation and crystallization propensity in frozen solutions, resulting in the loss of its stabilization function. In lyophilized formulations, sucrose has a higher crystallization propensity. Besides, its glass matrix is less homogeneous than that of trehalose, thus undermining its lyoprotectant function. Nevertheless, the hygroscopic nature of trehalose may result in high water absorption upon storage. Among all the CDs, the ß form is believed to have stronger interactions with proteins than the α- and γ-CDs. However, the stabilization effect, brought about by CD-protein interactions, is case-by-case - in some examples, such interactions can promote protein destabilization. The stabilization effect of hydroxypropyl-ß-cyclodextrin (HPßCD) has been extensively studied. Due to its amphiphilic nature, it can act as a surface-active agent in preventing interfacial stresses. Besides, it is a dual functional excipient in freeze dried formulations, acting as an amorphous bulking agent and lyoprotectant. Finally, dextrans, when combined with sucrose or trehalose, can be used to produce stable freeze dried protein formulations. A strong stabilization effect can be realized by low molecular weight dextrans. However, the terminal glucose in dextrans yields protein glycation, which warrants extra caution during formulation development.


Assuntos
Ciclodextrinas , Trealose , Trealose/química , Sacarose/química , Ciclodextrinas/química , Dextranos/química , Excipientes/química , Água/química , Liofilização
12.
J Pediatr ; 266: 113867, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38065280

RESUMO

OBJECTIVE: To test the effectiveness of a telemedicine-based program in reducing asthma morbidity among children who present to the emergency department (ED) for asthma, by facilitating primary care follow-up and promoting delivery of guideline-based care. STUDY DESIGN: We included children (3-12 years of age) with persistent asthma who presented to the ED for asthma, who were then randomly assigned to Telemedicine Enhanced Asthma Management through the Emergency Department (TEAM-ED) or enhanced usual care. TEAM-ED included (1) school-based telemedicine follow-ups, completed by a primary care provider, (2) point-of-care prompting to promote guideline-based care, and 3) an opportunity for 2 additional telemedicine follow-ups. The primary outcome was the mean number of symptom-free days (SFDs) over 2 weeks at 3, 6, 9, and 12 months. RESULTS: We included 373 children from 2016 through 2021 (participation rate 68%; 54% Black, 32% Hispanic, 77% public insurance; mean age, 6.4 years). Demographic characteristics and asthma severity were similar between groups at baseline. Most (91%) TEAM-ED children had ≥1 telemedicine visit and 41% completed 3 visits. At 3 months, caregivers of children in TEAM-ED reported more follow-up visits (66% vs 48%; aOR, 2.07; 95% CI, 1.28-3.33), preventive asthma medication actions (90% vs 79%; aOR, 3.28; 95% CI, 1.56-6.89), and use of a preventive medication (82% vs 69%; aOR, 2.716; 95% CI, 1.45-5.08), compared with enhanced usual care. There was no difference between groups in medication adherence or asthma morbidity. When only prepandemic data were included, there was greater improvement in SFDs over time for children in TEAM-ED vs enhanced usual care. CONCLUSIONS: TEAM-ED significantly improved follow-up and preventive care after an ED visit for asthma. We also saw improved SFDs with prepandemic data. The lack of overall improvement in morbidity and adherence indicates the need for additional ongoing management support. TRIAL REGISTRATION: NCT02752165.


Assuntos
Asma , Telemedicina , Criança , Humanos , Asma/prevenção & controle , Serviço Hospitalar de Emergência , Morbidade
13.
Biomacromolecules ; 25(1): 290-302, 2024 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-38065622

RESUMO

The prodrug strategy for its potential to enhance the pharmacokinetic and/or pharmacodynamic properties of drugs, especially chemotherapeutic agents, has been widely recognized as an important means to improve therapeutic efficiency. Irinotecan's active metabolite, 7-ethyl-10-hydroxycamptothecin (SN38), a borate derivative, was incorporated into a G-quadruplex hydrogel (GB-SN38) by the ingenious and simple approach. Drug release does not depend on carboxylesterase, thus bypassing the side effects caused by ineffective activation, but specifically responds to the ROS-overexpressed tumor microenvironment by oxidative hydrolysis of borate ester that reduces serious systemic toxicity from nonspecific biodistribution of SN38. Comprehensive spectroscopy was used to define the structural and physicochemical characteristics of the drug-loaded hydrogel. The GB-SN38 hydrogel's high level of biosafety and notable tumor-suppressive properties were proven in in vitro and in vivo tests.


Assuntos
Pró-Fármacos , Pró-Fármacos/química , Distribuição Tecidual , Boratos , Linhagem Celular Tumoral , Hidrogéis/farmacologia , Camptotecina/farmacologia
14.
J Clin Invest ; 134(3)2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38015626

RESUMO

Blood-brain barrier (BBB) disruption is a serious pathological consequence of traumatic brain injury (TBI), for which there are limited therapeutic strategies. Tissue inhibitor of metalloproteinase-2 (TIMP2), a molecule with dual functions of inhibiting MMP activity and displaying cytokine-like activity through receptor binding, has been reported to inhibit VEGF-induced vascular hyperpermeability. Here, we investigate the ability of TIMP2 to ameliorate BBB disruption in TBI and the underlying molecular mechanisms. Both TIMP2 and AlaTIMP2, a TIMP2 mutant without MMP-inhibiting activity, attenuated neurological deficits and BBB leakage in TBI mice; they also inhibited junctional protein degradation and translocation to reduce paracellular permeability in human brain microvascular endothelial cells (ECs) exposed to hypoxic plus inflammatory insult. Mechanistic studies revealed that TIMP2 interacted with α3ß1 integrin on ECs, inhibiting Src activation-dependent VE-cadherin phosphorylation, VE-cadherin/catenin complex destabilization, and subsequent VE-cadherin internalization. Notably, localization of VE-cadherin on the membrane was critical for TIMP2-mediated EC barrier integrity. Furthermore, TIMP2-mediated increased membrane localization of VE-cadherin enhanced the level of active Rac1, thereby inhibiting stress fiber formation. All together, our studies have identified an MMP-independent mechanism by which TIMP2 regulates EC barrier integrity after TBI. TIMP2 may be a therapeutic agent for TBI and other neurological disorders involving BBB breakdown.


Assuntos
Antígenos CD , Barreira Hematoencefálica , Lesões Encefálicas Traumáticas , Animais , Humanos , Camundongos , Barreira Hematoencefálica/metabolismo , Lesões Encefálicas Traumáticas/tratamento farmacológico , Lesões Encefálicas Traumáticas/genética , Lesões Encefálicas Traumáticas/metabolismo , Caderinas/genética , Caderinas/metabolismo , Células Endoteliais/metabolismo , Inibidor Tecidual de Metaloproteinase-2/genética , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Proteínas Proto-Oncogênicas pp60(c-src)/metabolismo
15.
Stem Cell Res Ther ; 14(1): 309, 2023 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-37880701

RESUMO

BACKGROUND: Pseudoenzymes, catalytically deficient variants of active enzymes, have a wide range of regulatory functions. ADP-ribosylhydrolase-like 1 (ADPRHL1), a pseudoenzyme belonging to a small group of ADP-ribosylhydrolase enzymes that lacks the amino acid residues necessary for catalytic activity, may have a significant role in heart development based on accumulating evidence. However, the specific function of ADPRHL1 in this process has not been elucidated. To investigate the role of ADPRHL1 in the heart, we generated the first in vitro human embryonic stem cell model with an ADPRHL1 knockout. METHOD: Using the CRISPR/Cas9 system, we generated ADPRHL1 knockout in the human embryonic stem cell (hESC) H9 line. The cells were differentiated into cardiomyocytes using a chemically defined and xeno-free method. We employed confocal laser microscopy to detect calcium transients and microelectrode array (MEA) to assess the electrophysiological activity of ADPRHL1 deficiency cardiomyocytes. Additionally, we investigated the cellular mechanism of ADPRHL1 by Bulk RNA sequencing and western blot. RESULTS: The results indicate that the absence of ADPRHL1 in cardiomyocytes led to adhered abnormally, as well as perturbations in calcium transients and electrophysiological activity. We also revealed that disruption of focal adhesion formation in these cardiomyocytes was due to an excessive upregulation of the ROCK-myosin II pathway. Notably, inhibition of ROCK and myosin II effectively restores focal adhesions in ADPRHL1-deficient cardiomyocytes and improved electrical conduction and calcium activity. CONCLUSIONS: Our findings demonstrate that ADPRHL1 plays a critical role in maintaining the proper function of cardiomyocytes by regulating the ROCK-myosin II pathway, suggesting that it may serve as a potential drug target for the treatment of ADPRHL1-related diseases.


Assuntos
Cálcio , Miócitos Cardíacos , N-Glicosil Hidrolases , Humanos , Cálcio/metabolismo , Diferenciação Celular , Células-Tronco Embrionárias/metabolismo , Miócitos Cardíacos/metabolismo , Miosina Tipo II/metabolismo , N-Glicosil Hidrolases/metabolismo
16.
Opt Express ; 31(18): 29061-29073, 2023 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-37710713

RESUMO

In the field of diamond MESFETs, this work is what we believe to be the first to investigate the optoelectronic properties of hydrogen-terminated polycrystalline diamond MESFETs under visible and near-UV light irradiation. It is shown that the diamond MESFETs are well suited for weak light detection in the near-ultraviolet region around the wavelength of 368 nm, with a responsivity of 6.14 × 106 A/W and an external quantum efficiency of 2.1 × 107 when the incident light power at 368.7 nm is only 0.75 µW/cm2. For incident light at 275.1 nm, the device's sensitivity and EQE increase as the incident light power increases; at an incident light power of 175.32 µW/cm2 and a VGS of -1 V, the device's sensitivity is 2.9 × 105 A/W and the EQE is 1.3 × 106. For incident light in the wavelength range of 660 nm to 404 nm with an optical power of 70 µW/cm2, the device achieves an average responsivity of 1.21 × 105 A/W. This indicates that hydrogen-terminated polycrystalline diamond MESFETs are suitable for visible and near-UV light detection, especially for weak near-UV light detection. However, the transient response test of the device shows a long relaxation time of about 0.2 s, so it is not yet suitable for high-speed UV communication or detection.

18.
Radiol Cardiothorac Imaging ; 5(3): e220092, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37404782

RESUMO

Purpose: To assess the efficacy of cardiac MRI stress T1 mapping in detecting ischemic and infarcted myocardium in a miniature-swine model, using pathologic findings as the reference standard. Materials and Methods: Ten adult male Chinese miniature swine, with coronary artery stenosis induced by an ameroid constrictor, and two healthy control swine were studied. Cardiac 3-T MRI rest and adenosine triphosphate stress T1 mapping and perfusion images, along with resting and late gadolinium enhancement images, were acquired at baseline and weekly up to 4 weeks after surgery or until humanely killed. A receiver operating characteristic analysis was used to analyze the performance of T1 mapping in the detection of myocardial ischemia. Results: In the experimental group, both the infarcted myocardium (ΔT1 = 10 msec ± 2 [SD]; ΔT1 percentage = 0.7% ± 0.1) and ischemic myocardium (ΔT1 = 10 msec ± 2; ΔT1 percentage = 0.9% ± 0.2) exhibited reduced T1 reactivity compared with the remote myocardium (ΔT1 = 53 msec ± 7; ΔT1 percentage = 4.7% ± 0.6) and normal myocardium (ΔT1 = 56 msec ± 11; ΔT1 percentage = 4.9% ± 1.1). Receiver operating characteristic analysis demonstrated high diagnostic performance of ΔT1 in detecting ischemic myocardium, with an area under the curve (AUC) of 0.84 (P < .001). Rest T1 displayed high diagnostic performance in detecting infarcted myocardium (AUC = 0.95; P < .001). When rest T1 and ΔT1 were combined, the diagnostic performance for both ischemic and infarcted myocardium were improved (AUCs, 0.89 and 0.97, respectively; all P < .001). The collagen volume fraction correlated with ΔT1, ΔT1 percentage, and Δ extracellular volume percentage (r = -0.70, -0.70, and -0.50, respectively; P = .001, .001, and .03, respectively). Conclusion: Using histopathologic validation in a swine model, noninvasive cardiac MRI stress T1 mapping demonstrated high performance in detecting ischemic and infarcted myocardium without the need for contrast agents.Keywords: Coronary Artery Disease, MRI, Myocardial Ischemia, Rest T1 Mapping, Stress T1 Mapping, Swine Model Supplemental material is available for this article. © RSNA, 2023See also commentary by Burrage and Ferreira in this issue.

19.
Medicine (Baltimore) ; 102(29): e34218, 2023 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-37478254

RESUMO

BACKGROUND: The anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitides are a collection of relatively rare autoimmune diseases characterized by the presence of ANCAs, predominantly against myeloperoxidase and proteinase 3. Multiple organs and systems are involved, but superficial lymph node involvement is rarely reported. CASE PRESENTATION: A 31-year-old woman initially presented with bilateral axillary lymphadenopathy and that the hilums were not clear. We report the rare case of a patient who presented with an ANCA-associated systemic vasculitis whose initial manifestation was axillary lymphadenopathy. The axillary lymph node needle biopsy specimens had reactive hyperplasia. One year later, the bilateral inguinal lymph nodes had similar morphological and structural changes, and laboratory test results showed renal insufficiency. A renal biopsy revealed the presence of sclerotic glomeruli, crescentic glomeruli, and fibrous crescentic glomeruli, but no deposition of immunocomplex or complement. Finally, the patient was treated with prednisone and mycophenolate mofetil. As the laboratory indicators normalized, so did the sizes of the axillary lymph nodes. A subsequent laboratory examination showed that in addition to urine protein all indicators had normalized, ultrasonography showed slight enlargement of unilateral axillary lymph nodes and normal hilum structure. CONCLUSIONS: Superficial lymphadenopathy is very rare in ANCA-associated systemic vasculitis. Studying this case improves our understanding of the initial manifestations of ANCA-associated vasculitis and may help provide accurate early diagnosis, thus allowing timely treatment and improved patient prognosis.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Glomerulonefrite , Linfadenopatia , Feminino , Humanos , Adulto , Anticorpos Anticitoplasma de Neutrófilos , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Glomérulos Renais/patologia , Linfadenopatia/patologia
20.
ACS Appl Mater Interfaces ; 15(30): 36602-36610, 2023 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-37467461

RESUMO

Perovskite light-emitting diodes (LEDs) have attracted extensive attention in recent years due to their outstanding performance and promise in lighting and display applications. However, the fabrication of perovskite LEDs usually requires a low-humidity atmosphere, which is unfavorable for industrial production. Herein, we report an effective strategy to fabricate highly luminescent quasi two-dimensional CsPbBr3 perovskite films in an ambient atmosphere with a humidity up to 60%. We reveal that the hole transport layer (HTL) plays a significant role in the morphology and optical properties of the perovskite films. Using hydrophobic self-assembled monolayer materials as HTLs can remarkably improve the quality of the perovskite films processed in high humidity air. The resultant perovskite LEDs show reduced leakage current and significantly enhanced performance. Furthermore, surface treatment is conducted to prevent water invasion and promote radiative recombination in perovskite films and LEDs. Eventually, the perovskite LEDs exhibit bright green emission with an external quantum efficiency of 4.87%. The present work provides a feasible pathway to overcome the humidity limitation for obtaining bright perovskite films and LEDs, which would contribute to further reducing the fabrication cost of perovskite LEDs and promoting their applications.

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