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1.
Int Immunopharmacol ; 138: 112645, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38972208

RESUMO

BACKGROUND: Pulmonary fibrosis is a progressive disease with high incidence and poor prognosis. It is urgent to explore new therapeutic methods for pulmonary fibrosis. As a new treatment method, gene therapy has attracted more and more attention. CCDC59 is a transcriptional coactivator of SP-B and SP-C. Our study mainly aims to explore the effect of overexpression of CCDC59 gene in pulmonary fibrosis of mice. METHODS: CCDC59 overexpressing lentivirus was constructed and then concentrated. RT-qPCR, Western blotting, and immunofluorescence assays were used to detect the expression of CCDC59, SP-B and SP-C protein in cell line and lung tissues after infected with lentivirus. Immunohistochemical staining and hematoxylin-eosin staining assays were used to assess the degree of fibrosis and ELISA assay was used to detect the concentrations of inflammatory factors, SP-B, and SP-C in bronchoalveolar lavage fluid of mice. Dynamic changes of mice lung function at various time points were assessed by lung function test assay. HIPPO pathway and proliferation capacity of alveolar type II epithelial cells were evaluated by immunofluorescence staining and Western blotting. RESULTS: Results showed that endotracheal instillation of CCDC59 overexpressed lentivirus significantly alleviated bleomycin-induced inflammation and pulmonary fibrosis in mice. Overexpression of CCDC59 protein in type II alveolar epithelial cells can enhance the expression of SP-B and SP-C. Overexpression of CCDC59 protein significantly protected against pulmonary inflammatory response and improved lung function of mice. Overexpression of CCDC59 protein significantly alleviated the hyperactivation of HIPPO pathway and increased the proliferative capacity of type II alveolar epithelial cells in lung. CONCLUSION: CCDC59 can alleviate inflammation and pulmonary fibrosis in mice by upregulating the expression of SP-B and SP-C in type II alveolar epithelial cells and alleviating the hyperactivation of HIPPO pathway. Our study offers a new potential treatment for pulmonary fibrosis.

2.
Biochemistry ; 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38985857

RESUMO

The C-C motif chemokine receptor 8 (CCR8) is a class A G-protein-coupled receptor that has emerged as a promising therapeutic target in cancer and autoimmune diseases. In the present study, we solved the cryo-electron microscopy (cryo-EM) structure of the human CCR8-Gi complex in the absence of a ligand at 2.58 Å. Structural analysis and comparison revealed that our apo CCR8 structure undergoes some conformational changes and is similar to that in the CCL1-CCR8 complex structure, indicating an active state. In addition, the key residues of CCR8 involved in the recognition of LMD-009, a potent nonpeptide agonist, were investigated by mutating CCR8 and testing the calcium flux induced by LMD-009-CCR8 interaction. Three mutants of CCR8, Y1133.32A, Y1724.64A, and E2867.39A, showed a dramatically decreased ability in mediating calcium mobilization, indicating their key interaction with LMD-009 and key roles in activation. These structural and biochemical analyses enrich molecular insights into the agonism and activation of CCR8 and will facilitate CCR8-targeted therapy.

3.
Cell Rep ; 43(7): 114487, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38996071

RESUMO

The integrated stress response (ISR) is activated in response to intrinsic and extrinsic stimuli, playing a role in tumor progression and drug resistance. The regulatory role and mechanism of ISR in liver cancer, however, remain largely unexplored. Here, we demonstrate that OTU domain-containing protein 3 (OTUD3) is a deubiquitylase of eukaryotic initiation factor 2α (eIF2α), antagonizing ISR and suppressing liver cancer. OTUD3 decreases interactions between eIF2α and the kinase EIF2ΑK3 by removing K27-linked polyubiquitylation on eIF2α. OTUD3 deficiency in mice leads to enhanced ISR and accelerated progression of N-nitrosodiethylamine-induced hepatocellular carcinoma. Additionally, decreased OTUD3 expression associated with elevated eIF2α phosphorylation correlates with the progression of human liver cancer. Moreover, ISR activation due to decreased OTUD3 expression renders liver cancer cells resistant to sorafenib, while the combined use of the ISR inhibitor ISRIB significantly improves their sensitivity to sorafenib. Collectively, these findings illuminate the regulatory mechanism of ISR in liver cancer and provide a potential strategy to counteract sorafenib resistance.

4.
PLoS Pathog ; 20(7): e1012256, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39024394

RESUMO

African swine fever (ASF) is a highly contagious, fatal disease of pigs caused by African swine fever virus (ASFV). The complexity of ASFV and our limited understanding of its interactions with the host have constrained the development of ASFV vaccines and antiviral strategies. To identify host factors required for ASFV replication, we developed a genome-wide CRISPR knockout (GeCKO) screen that contains 186,510 specific single guide RNAs (sgRNAs) targeting 20,580 pig genes and used genotype II ASFV to perform the GeCKO screen in wild boar lung (WSL) cells. We found that knockout of transmembrane protein 239 (TMEM239) significantly reduced ASFV replication. Further studies showed that TMEM239 interacted with the early endosomal marker Rab5A, and that TMEM239 deletion affected the co-localization of viral capsid p72 and Rab5A shortly after viral infection. An ex vivo study showed that ASFV replication was significantly reduced in TMEM239-/- peripheral blood mononuclear cells (PBMCs) from TMEM239 knockout piglets. Our study identifies a novel host factor required for ASFV replication by facilitating ASFV entry into early endosomes and provides insights for the development of ASF-resistant breeding.

5.
Int J Cardiol ; 413: 132359, 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39004352

RESUMO

BACKGROUND: Studies have revealed the beneficial effects of sodium-glucose co-transporter 2 inhibitors (SGLT2i) for the treatment of heart failure (HF) regardless of the presence of diabetes. Besides, SGLT2i can decrease the incidence of atrial fibrillation (AF) in a broad population. However, the effects of SGLT2i on AF recurrence following catheter ablation (CA) remain uncertain. Therefore, this meta-analysis was undertaken to elucidate the effects of SGLT2i on AF recurrence after CA in AF patients. METHODS: A comprehensive search of PubMed, Embase, and Cochrane library was conducted for relevant studies, encompassing data from inception until March 20, 2024. The data were pooled using a fixed-effects model if the I2 value was <50%; otherwise, a random-effects model was adopted. RESULTS: One randomized controlled trial (RCT) and five observational studies involving 5623 patients with AF who underwent CA were included. SGLT2i treatment was associated with a significantly lower rate of AF recurrence (odds ratio [OR] = 0.45, 95% confidence interval [CI]: 0.31-0.66). Subgroup analysis demonstrated that patients treated with SGLT2i exhibited a lower incidence of AF recurrence compared to those treated with dipeptidyl peptidase-4 inhibitors (DPP4i). The favorable effects of SGLT2i on AF recurrence were more pronounced in male patients and patients with persistent AF. CONCLUSIONS: This meta-analysis provided evidence supporting the effectiveness of SGLT2i in reducing the risk of AF recurrence after CA in AF patients. SGLT2i may serve as an additional therapy option in this population.

6.
Br J Dermatol ; 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39009432

RESUMO

BACKGROUND: Skin fibrosis is the most typical pathological manifestation of systemic sclerosis (SSc) and localized scleroderma (LS) with unclear etiology and few effective treatments. Though excessive collagen secretion by fibroblasts is the primary cause of skin fibrosis, many lines of evidence suggested that vascular damage was the initiating event and various cell types along with fibroblasts worked together to contribute to the pathogenesis of skin fibrosis. OBJECTIVES: We sought to explore the relationships between vascular endothelial cell lesions and immune cell infiltration, along with the cell-cell interactions among various cell types within the fibrotic skin ecosystem. METHODS: Single-cell RNA-seq (10x Genomics) was performed on skin biopsies of 3 healthy donors and 7 SSc patients in Chinese. The additional 3 localized scleroderma patients' data from NCBI database (GSE160536) were integrated by Harmony. CellChat package (v1.5.0) was applied to analyze cell communication network. Transwell assay and subcutaneous bleomycin (BLM) injection in mice were used to explore the role of ACKR1 on immune cell infiltration. Milo single-cell western blot was applied to show the activation of fibroblast subclusters. RESULTS: A total of 62,295 cells were obtained and subpopulations of stromal and immune cells were identified. Interaction network analysis revealed that multiple chemokines secreted by macrophages, pericytes, and pro-inflammatory fibroblasts could bind with Duffy antigen/receptor for chemokines (ACKR1), which is highly expressed on ACKR1+ endothelial cells of lesion skin. Transwell assay revealed that over-expressed ACKR1 in HUVEC facilitated leukocyte infiltration under the treatment of IL8. The BLM mice showed enhanced ACKR1 expression, massive immune cell infiltration, and fibrosis in skin, which could be attenuated by ACKR1 inhibition. Furthermore, infiltrated macrophages with TGFB1 or PDGFB high production could activate SFRP2/ASPN+ fibroblasts to contribute to excessive accumulation of extracellular matrix (ECM), and the SOX4-ASPN axis plays an important role in the TGF-ß signaling cascade and the etiology of skin fibrosis. CONCLUSIONS: Our results reveal that highly expressed ACKR1 in endothelial cells of fibrotic skin tissue promotes immune cell infiltration, and SFRP2/ASPN+ fibroblasts synergize to exacerbate skin fibrosis.

7.
Org Lett ; 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39018122

RESUMO

Friedel-Crafts acylation is usually promoted by Lewis acids or Brønsted acids. In this work, a novel acylation of arenes with a highly electrophilic acylphosphonium salt was developed. The alkylation of the phosphorus atom in acylphosphines generated a neutral trivalent phosphine as a good leaving group and triggered the high electrophilicity of the acylphosphonium salt. Using acylphosphonium salts, 38 examples of acylations of arenes, alcohols, phenol, amines, thioalcohols, and even polystyrene were achieved. The acylation of arenes was monitored by 31P nuclear magnetic resonance and disclosed the existence of an acylphosphonium intermediate. The electrophilic capability of the acylphosphonium salt was ranked by the following series of controlled reactions: AcPR+ ≈ AcOTf > AcI > AcCl.

8.
J Biol Methods ; 11: e99010009, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38988498

RESUMO

The rapid identification SARS-CoV-2 virus has become the basis for the control of the COVID-19 outbreak. The rapid antigen tests for SARS-CoV-2 are quick, widely available, and inexpensive. Rapid antigen tests have gradually replaced the time-consuming and costly RT-PCR. Currently, although several RAT kits have been extensively used for the diagnosis of COVID-19, validity data are limited due to the inconsistent sensitivity and poor reproducibility. Meanwhile, WHO does not recommend specific commercial RAT kits. Therefore, it is crucial to establish a method to evaluate the effectiveness of different rapid antigen tests kits. This study aimed to develop an evaluation system for rapid antigen tests to provide an efficient and accurate technique for screening SARS-CoV-2 antigen detection kits. Given large number of rapid antigen tests kits available, this study only focused on those that are representative and commonely used in China. By minimzing biases through randomization, concealment, and blinding, we eventually found that the Test 1 had the lowest sensitivity and the Test VI had the highest sensitivity. This study provided an evaluation platform that can potentially serve as a reference for COVID-19 diagnostic strategies.

9.
Artigo em Inglês | MEDLINE | ID: mdl-38976462

RESUMO

Ultrasound Localization Microscopy (ULM), an emerging medical imaging technique, effectively resolves the classical trade-off between resolution and penetration inherent in traditional ultrasound imaging, opening up new avenues for noninvasive observation of the microvascular system. However, traditional microbubble tracking methods encounter various practical challenges. These methods typically entail multiple processing stages, including intricate steps like pairwise correlation and trajectory optimization, rendering real-time applications unfeasible. Furthermore, existing deep learning-based tracking techniques neglect the temporal aspects of microbubble motion, leading to ineffective modeling of their dynamic behavior. To address these limitations, this study introduces a novel approach called the Gated Recurrent Unit (GRU)-based Multitasking Temporal Neural Network (GRU-MT). GRU-MT is designed to simultaneously handle microbubble trajectory tracking and trajectory optimization tasks. Additionally, we enhance the nonlinear motion model initially proposed by Piepenbrock et al. to better encapsulate the nonlinear motion characteristics of microbubbles, thereby improving trajectory tracking accuracy. In this study, we perform a series of experiments involving network layer substitutions to systematically evaluate the performance of various temporal neural networks, including Recurrent Neural Networks (RNN), Long Short-Term Memory (LSTM), GRU, Transformer, and its bidirectional counterparts, on the microbubble trajectory tracking task. Concurrently, the proposed method undergoes qualitative and quantitative comparisons with traditional microbubble tracking techniques. The experimental results demonstrate that GRU-MT exhibits superior nonlinear modeling capabilities and robustness, both in simulation and in vivo dataset. Additionally, it achieves reduced trajectory tracking errors in shorter time intervals, underscoring its potential for efficient microbubble trajectory tracking. Model code is open-sourced at https://github.com/zyt-Lib/GRU-MT.

10.
Artigo em Inglês | MEDLINE | ID: mdl-39014141

RESUMO

The electrochemical advanced oxidation process (EAOP) has shown significant promise in the field of refractory organic wastewater treatment due to its high efficiency and environmentally friendly nature. In this study, Ti/Sb-SnO2 electrodes with varying proportions of Hf were prepared using the sol-gel method. The addition of Hf transformed the original collapsing and broken surface into a flat and regular surface. The results demonstrated that Ti/Sb-SnO2-Hf electrode doped with 6% Hf exhibited a higher oxygen evolution potential (OEP) and excellent stability. The OEP increased from 2.315 V without Hf-doping to 2.482 V, and the corresponding actual life was 321.05% higher than that without Hf. The current density (5-40 mA·cm-2), electrolyte concentration (0.02-0.2 mol·L-1), pH (3-11), and initial pollutant concentration (5-80 mg·L-1) were evaluated to confirm the tetracycline (TC) degradation characterization of Ti/Sb-SnO2-6%Hf electrodes. It was concluded that under the optimal degradation conditions, the removal rate of TC could reach 99.66% within 2 h. The degradation of TC follows first-order reaction kinetics. The oxidative degradation of TC was achieved through indirect oxidation, with ·OH playing a dominant role. TC's electrochemical oxidation degradation pathway has been proposed: Based on LC-MS results, three main pathways are speculated. During the electrocatalytic oxidation process, decarboxylation, deamidation, and ring-opening reactions occur under ·OH attack, producing intermediate compounds with m/z values of 427, 433, 350, 246, 461, 424, 330, 352, 309, 263, and 233. These intermediates are further oxidized to intermediate compounds with an m/z value of 218. This work introduces a new efficient anode electrochemical catalyst for the degradation of TC, providing a strategy for industrial applications.

11.
Artigo em Inglês | MEDLINE | ID: mdl-39014911

RESUMO

BACKGROUND: Several types of human papillomavirus (HPV) vaccines have been approved for use in adolescent girls in China. These vaccines are regulated as non-National Immunisation Program vaccines and are optional and generally fully self-paid by vaccinees. OBJECTIVE: To assess parents' demand for HPV vaccination by eliciting their willingness-to-pay for their adolescent daughters to be vaccinated against HPV and to examine the determinants of demand for HPV vaccination in China. METHODS: A contingent valuation survey was conducted across three cities in Shandong Province in eastern China. We selected 11 junior middle schools with different socioeconomic features and randomly selected 6 classes in each school, and questionnaires were distributed to all girls aged 12-16 in the 66 classes for their parents to complete. A payment card approach was used to elicit parental willingness-to-pay for HPV vaccination for their daughters. We also collected a wide array of socioeconomic and psychological variables and interval regressions were applied to examine the determinants of parental willingness-to-pay. RESULTS: A total of 1074 eligible parents who completed valid questions were included in analyses. Over 85% of parents believed HPV vaccines were, in general, necessary and beneficiary. However, only around 10% believed that their daughters would be infected by HPV. About 8% of parents would not accept HPV vaccine even if the vaccine were free mainly due to concerns about the potential side effects and vaccine safety and quality issues, and 27.37% would only accept the vaccine if it were free. The median willingness-to-pay was 300 CNY (42 USD). Several factors were positively correlated with higher willingness-to-pay: income, urban residence (relative to rural residence), mothers (relative to fathers), parents' beliefs about vaccine benefits, whether they should make decisions for their daughters, and whether their daughters would be susceptible to HPV. Though education-level was not significantly correlated with willingness-to-pay in the main regressions, a subgroup analysis revealed interesting dynamics in the relation between education and willingness-to-pay across different income-levels. CONCLUSIONS: There is a large gap between parents' willingness-to-pay and the market price of HPV vaccine for girls in China. Parents generally believed the HPV vaccines were beneficial and necessary but when asked for their daughters, most parents did not believe their daughters would be infected by HPV despite the high prevalence in China. Future focus should be on ensuring the provision of accurate health information about HPV prevalence, vaccine quality, and safety to promote vaccine uptake, and promotional efforts tailored to different income groups might yield better effects. Government involvement in negotiating more widely acceptable and affordable prices or subsidising may be necessary for protecting high-risk population groups.

12.
World J Gastroenterol ; 30(23): 3005-3015, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38946876

RESUMO

BACKGROUND: Gastric cancer (GC) is the most common malignant tumor and ranks third for cancer-related deaths among the worldwide. The disease poses a serious public health problem in China, ranking fifth for incidence and third for mortality. Knowledge of the invasive depth of the tumor is vital to treatment decisions. AIM: To evaluate the diagnostic performance of double contrast-enhanced ultrasonography (DCEUS) for preoperative T staging in patients with GC by comparing with multi-detector computed tomography (MDCT). METHODS: This single prospective study enrolled patients with GC confirmed by preoperative gastroscopy from July 2021 to March 2023. Patients underwent DCEUS, including ultrasonography (US) and intravenous contrast-enhanced ultrasonography (CEUS), and MDCT examinations for the assessment of preoperative T staging. Features of GC were identified on DCEUS and criteria developed to evaluate T staging according to the 8th edition of AJCC cancer staging manual. The diagnostic performance of DCEUS was evaluated by comparing it with that of MDCT and surgical-pathological findings were considered as the gold standard. RESULTS: A total of 229 patients with GC (80 T1, 33 T2, 59 T3 and 57 T4) were included. Overall accuracies were 86.9% for DCEUS and 61.1% for MDCT (P < 0.001). DCEUS was superior to MDCT for T1 (92.5% vs 70.0%, P < 0.001), T2 (72.7% vs 51.5%, P = 0.041), T3 (86.4% vs 45.8%, P < 0.001) and T4 (87.7% vs 70.2%, P = 0.022) staging of GC. CONCLUSION: DCEUS improved the diagnostic accuracy of preoperative T staging in patients with GC compared with MDCT, and constitutes a promising imaging modality for preoperative evaluation of GC to aid individualized treatment decision-making.


Assuntos
Meios de Contraste , Tomografia Computadorizada Multidetectores , Estadiamento de Neoplasias , Neoplasias Gástricas , Ultrassonografia , Humanos , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Pessoa de Meia-Idade , Masculino , Feminino , Meios de Contraste/administração & dosagem , Estudos Prospectivos , Idoso , Ultrassonografia/métodos , Ultrassonografia/estatística & dados numéricos , Tomografia Computadorizada Multidetectores/métodos , Adulto , China/epidemiologia , Gastroscopia/métodos , Estômago/diagnóstico por imagem , Estômago/patologia , Estômago/cirurgia , Idoso de 80 Anos ou mais
14.
Food Chem ; 457: 140148, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38908245

RESUMO

The inclusion complex (IC) was successfully obtained by encapsulating glycerol monolaurate (GML) into the cavity of hydroxypropyl-ß-cyclodextrin (HP-ß-CD). Compared with solubility of pure GML <80 µg/mL in water, and the water-solubility of encapsulated GML was significantly improved and reached to 270,000 µg/mL. IC can form nanoparticles by self-assembly, probably assigned to its strong capability to form micellar-type aggregates. A Higuchi's AL-type phase-solubility diagram indicated the strong interaction between host and guest molecules with the formation of 1:1 GML/HP-ß-CD complex and the stability constant at 6248 L/mol. Compared with pure GML, encapsulated GML at the same concentration can also show good antibacterial capabilities against S. aureus and E. coli in sterile water, and the effective preservative capabilities towards beef meatballs. The boosted enhancement in water-solubility of GML and the effective antibacterial capabilities endowed IC with potential in the application of food decontamination.

15.
Nat Sci Sleep ; 16: 653-662, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38836215

RESUMO

Objective: Compared to low arousal threshold (AT), high AT is an easily overlooked characteristic for obstructive sleep apnea (OSA) severity estimation. This study aims to evaluate the relationship between high AT, hypertension and diabetes in OSA, compared to those with apnea-hypopnea index (AHI). Methods: A total of 3400 adults diagnosed with OSA were retrospectively recruited. Propensity score matching (PSM) was conducted to further categorize these patients into the low and high AT groups based on the strategy established by previous literature. The different degrees of AHI and quantified AT (AT score) were subsequently measured. The correlation of AT and AHI with the occurrence of various comorbidities in OSA was estimated by logistic regression analysis with odds ratio (OR). Results: After PSM, 938 pairs of patients arose. The median AT score of high and low AT group was 21.7 and 12.2 scores, and the adjusted OR of high AT for hypertension and diabetes was 1.31 (95% CI = 1.07-1.62, P < 0.01) and 1.45 (95% CI = 1.01-2.08, P < 0.05), respectively. Compared to low AT score group, the OR significantly increased in patients with very high AT score (30 ≤ AT score), especially for diabetes (OR = 1.79, 95% CI = 1.02-3.13, P < 0.05). The significant association was not observed in AHI with increasing prevalent diabetes. Conclusion: Higher AT is significantly associated with increased prevalence of hypertension and diabetes in patients with OSA. Compared with AHI, AT score is a potentially comprehensive indicator for better evaluating the relationship between OSA and related comorbidities.

16.
J Neuroeng Rehabil ; 21(1): 98, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38851703

RESUMO

PURPOSE: This pilot study aimed to investigate the effects of REX exoskeleton rehabilitation robot training on the balance and lower limb function in patients with sub-acute stroke. METHODS: This was a pilot, single-blind, randomized controlled trial. Twenty-four patients with sub-acute stroke (with the course of disease ranging from 3 weeks to 3 months) were randomized into two groups, including a robot group and a control group. Patients in control group received upright bed rehabilitation (n = 12) and those in robot group received exoskeleton rehabilitation robot training (n = 12). The frequency of training in both groups was once a day (60 min each) for 5 days a week for a total of 4 weeks. Besides, the two groups were evaluated before, 2 weeks after and 4 weeks after the intervention, respectively. The primary assessment index was the Berg Balance Scale (BBS), whereas the secondary assessment indexes included the Fugl-Meyer Lower Extremity Motor Function Scale (FMA-LE), the Posture Assessment Scale for Stroke Patients (PASS), the Activities of Daily Living Scale (Modified Barthel Index, MBI), the Tecnobody Balance Tester, and lower extremity muscle surface electromyography (sEMG). RESULTS: The robot group showed significant improvements (P < 0.05) in the primary efficacy index BBS, as well as the secondary efficacy indexes PASS, FMA-LE, MBI, Tecnobody Balance Tester, and sEMG of the lower limb muscles. Besides, there were a significant differences in BBS, PASS, static eye-opening area or dynamic stability limit evaluation indexes between the robotic and control groups (P < 0.05). CONCLUSIONS: This is the first study to investigate the effectiveness of the REX exoskeleton rehabilitation robot in the rehabilitation of patients with stroke. According to our results, the REX exoskeleton rehabilitation robot demonstrated superior potential efficacy in promoting the early recovery of balance and motor functions in patients with sub-acute stroke. Future large-scale randomized controlled studies and follow-up assessments are needed to validate the current findings. CLINICAL TRIALS REGISTRATION: URL: https://www.chictr.org.cn/index.html.Unique identifier: ChiCTR2300068398.


Assuntos
Exoesqueleto Energizado , Extremidade Inferior , Equilíbrio Postural , Robótica , Reabilitação do Acidente Vascular Cerebral , Humanos , Reabilitação do Acidente Vascular Cerebral/instrumentação , Reabilitação do Acidente Vascular Cerebral/métodos , Masculino , Projetos Piloto , Feminino , Pessoa de Meia-Idade , Extremidade Inferior/fisiopatologia , Equilíbrio Postural/fisiologia , Método Simples-Cego , Robótica/instrumentação , Idoso , Adulto , Acidente Vascular Cerebral/fisiopatologia , Eletromiografia , Resultado do Tratamento , Recuperação de Função Fisiológica
17.
Plant J ; 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38865101

RESUMO

Anthocyanin is an important pigment responsible for plant coloration and beneficial to human health. Kale (Brassica oleracea var. acephala), a primary cool-season flowers and vegetables, is an ideal material to study anthocyanin biosynthesis and regulation mechanisms due to its anthocyanin-rich leaves. However, the underlying molecular mechanism of anthocyanin accumulation in kale remains poorly understood. Previously, we demonstrated that BoDFR1 is a key gene controlling anthocyanin biosynthesis in kale. Here, we discovered a 369-bp InDel variation in the BoDFR1 promoter between the two kale inbred lines with different pink coloration, which resulted in reduced transcriptional activity of the BoDFR1 gene in the light-pink line. With the 369-bp insertion as a bait, an R2R3-MYB repressor BoMYB4b was identified using the yeast one-hybrid screening. Knockdown of the BoMYB4b gene led to increased BoDFR1 expression and anthocyanin accumulation. An E3 ubiquitin ligase, BoMIEL1, was found to mediate the degradation of BoMYB4b, thereby promoting anthocyanin biosynthesis. Furthermore, the expression level of BoMYB4b was significantly reduced by light signals, which was attributed to the direct repression of the light-signaling factor BoMYB1R1 on the BoMYB4b promoter. Our study revealed that a novel regulatory module comprising BoMYB1R1, BoMIEL1, BoMYB4b, and BoDFR1 finely regulates anthocyanin accumulation in kale. The findings aim to establish a scientific foundation for genetic improvement of leaf color traits in kale, meanwhile, providing a reference for plant coloration studies.

18.
Acad Radiol ; 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38852002

RESUMO

RATIONALE AND OBJECTIVES: The pericoronary fat attenuation index (FAI) values around plaques may reveal the relationship between periplaque vascular inflammation and different plaque component volume fractions. We aimed to evaluate the potential associations between periplaque FAI values and plaque component volume fractions. MATERIALS AND METHODS: 496 patients (1078 lesions) with coronary artery disease, who underwent computed tomography angiography (CCTA) between September 2022 and August 2023, were analyzed retrospectively. Each lesion was characterized and the plaque component volume fractions and periplaque FAI values were measured. Multiple linear regression, weighted quantile sum (WQS) regression, and quantile g-computation (Qgcomp) were used to explore the relationship between plaque component volume fractions and the risk of elevated periplaque FAI values. RESULTS: After adjusting for clinical characteristics, multiple linear regression identified that lipid components volume fraction (ß = 0.162, P < 0.001) were independent risk factors for elevated periplaque FAI values whereas calcified components volume fraction (ß = -0.066, P = 0.025) were independent protective factors. The WQS regression models indicated an increase in the overall confounding effect of the adjusted lipid indices and plaque composition volume fraction on the risk of elevated periplaque FAI values (P = 0.004). Qgcomp analysis indicated lipid component volume fraction and calcified component volume fraction was positively and negatively correlated with elevated plaque FAI values, respectively (all P < 0.05). CONCLUSIONS: Periplaque FAI values quantified by CCTA were strongly correlated with lipid and calcification component volume fractions.

19.
BMC Med Genomics ; 17(1): 155, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38840095

RESUMO

BACKGROUND: Previous studies have implicated inherited mutations in mitochondrial DNA (mtDNA) in sensorineural hearing loss (SNHL). However, the definitive association between mitochondrial 12S rRNA (MT-RNR1) variants and hearing loss in the population has not been well established, particularly in Asia. The objective of this retrospective cohort study was to assess the association between MT-RNR1 variants and the risk of SNHL in patients in Taiwan. METHODS: The cohort included 306,068 participants from Taiwan between January 2003 and December 2020. Participants were classified based on genetic variants, particularly mitochondrial mutations (rs267606618, rs267606619, rs267606617). MT-RNR1 variant cases were matched 1:10 with non-mutant patients by age, gender, and visit year, excluding those with pre-existing hearing loss. The primary endpoint was SNHL, identified using specific ICD-TM codes with a 90% positive predictive value. Medication exposure history was determined via self-report or electronic medical records in the hospital. Cox proportional hazard regression models were used to assess the association between MT-RNR1 variants and hearing loss, adjusting for various covariates. Kaplan-Meier survival curves and log-rank tests compared hearing loss incidence between groups. RESULTS: The mean age of the mtDNA variants group is 32.4 years, with a standard deviation of 19.2 years. The incidence density of hearing loss for the mutation group was 36.42 per 10,000 person-years (95% Confidence Interval [CI], 27.21-47.73), which was higher than the 23.77per 10,000 person-years (95% CI, 21.32-26.42) in the wild-type group (p = 0.0036). Additionally, diabetes mellitus was associated with an increased risk of developing SNHL in individuals with MT-RNR1 variants (adjusted hazard ratio = 1.76 [95% CI, 1.00-3.09], p < 0.05). CONCLUSION: This study highlights the increased risk of hearing loss in patients carrying MT-RNR1 variants, particularly those with diabetes mellitus. Future research that integrates genetic and clinical data is crucial for developing more precise interventions to monitor and treat hearing loss in this vulnerable population.


Assuntos
Mutação , RNA Ribossômico , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , DNA Mitocondrial/genética , Predisposição Genética para Doença , Perda Auditiva/genética , Perda Auditiva Neurossensorial/genética , Estudos Retrospectivos , Fatores de Risco , RNA Ribossômico/genética , Taiwan/epidemiologia , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Peptídeos/genética , Peptídeos/metabolismo
20.
Colloids Surf B Biointerfaces ; 241: 114061, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38941651

RESUMO

Responsive release systems have received extensive attention to enhance pesticide utilization efficiency and reduce environmental pollution. In this study, pH/GSH dual responsive release system based on brush-like silica (bSiO2) carriers was constructed to enhance the utilization of pesticides. The bSiO2 carriers present core-shell structure, length of 550 nm, diameter of 350 nm and shell thickness of 100 nm. The carrier had a high pesticide loading (20.0 %, w/w) for dinotefuran (Din). After loading Din, zein was covalently linked with cysteine-bridge to seal the loaded pesticides (namely Din@bSiO2@Zein). The Din@bSiO2@Zein exhibited superior foliar affinity, retention and photostability, and retention rate still remain above 95 % with 220 min UV irradiation. Din@bSiO2@Zein displayed pH/GSH responsive release and the cumulative release within 92 h was up to 81 % under pH=9/CGSH=6 mM, mimicking the microenvironment of lepidopteran. The Din@bSiO2@Zein possessed good control efficacy against Plutella xylostella. Appreciably, Din@bSiO2@Zein could be transported bi-directionally to various regions of tobacco plants within 24 h, which had potential to promote pesticide efficacy. This work offers a strategy to minimize the pesticide dosage and encourage sustainable agricultural development.

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