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1.
Adv Sci (Weinh) ; : e2404558, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965690

RESUMO

Harmonic generation and utilization are significant topics in nonlinear science. Although the progress in the microwave region has been expedited by the development of time-modulated metasurfaces, one major issue of these devices is the strong entanglement of multiple harmonics, leading to criticism of their use in frequency-division multiplexing (FDM) applications. Previous studies have attempted to overcome this limitation, but they suffer from designing complexity or insufficient controlling capability. Here a new space-time-coding metasurface (STCM) is proposed to independently and precisely synthesize not only the phases but also the amplitudes of various harmonics. This promising feature is successfully demonstrated in wireless space- and frequency-division multiplexing experiments, where modulated and unmodulated signals are simultaneously transmitted via different harmonics using a shared STCM. To illustrate the advantages, binary frequency shift keying (BFSK) and quadrature phase shift keying (QPSK) modulation schemes are respectively implemented. Behind the intriguing functionality, the mechanism of the space-time coding strategy and the analytical designing method are elaborated, which are validated numerically and experimentally. It is believed that the achievements can potentially propel the time-vary metasurfaces in the next-generation wireless applications.

2.
World J Gastrointest Oncol ; 16(6): 2541-2554, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38994140

RESUMO

BACKGROUND: Stage classification for Siewert II adenocarcinoma of the esophagogastric junction (AEG) treated with neoadjuvant chemotherapy (NAC) has not been established. AIM: To investigate the optimal stage classification for Siewert II AEG with NAC. METHODS: A nomogram was established based on Cox regression model that analyzed variables associated with overall survival (OS) and disease-specific survival (DSS). The nomogram performance in terms of discrimination and calibration ability was evaluated using the likelihood-ratio test, Akaike information criterion, Harrell concordance index, time-receiver operating characteristic curve, and decision curve analysis. RESULTS: Data from 725 patients with Siewert type II AEG who underwent neoadjuvant therapy and gastrectomy were obtained from the Surveillance, Epidemiology, and End Results database. Univariate and multivariate analyses revealed that sex, marital status, race, ypT stage, and ypN stage were independent prognostic factors of OS, whereas sex, race, ypT stage, and ypN stage were independent prognostic factors for DSS. These factors were incorporated into the OS and DSS nomograms. Our novel nomogram model performed better in terms of OS and DSS prediction compared to the 8th American Joint Committee of Cancer pathological staging system for esophageal and gastric cancer. Finally, a user-friendly web application was developed for clinical use. CONCLUSION: The nomogram established specifically for patients with Siewert type II AEG receiving NAC demonstrated good prognostic performance. Validation using external data is warranted before its widespread clinical application.

3.
Cell Death Dis ; 15(7): 505, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39013891

RESUMO

During oxidative phosphorylation, mitochondria continuously produce reactive oxygen species (ROS), and untimely ROS clearance can subject mitochondria to oxidative stress, ultimately resulting in mitochondrial damage. Mitophagy is essential for maintaining cellular mitochondrial quality control and homeostasis, with activation involving both ubiquitin-dependent and ubiquitin-independent pathways. Over the past decade, numerous studies have indicated that different forms of regulated cell death (RCD) are connected with mitophagy. These diverse forms of RCD have been shown to be regulated by mitophagy and are implicated in the pathogenesis of a variety of diseases, such as tumors, degenerative diseases, and ischemia‒reperfusion injury (IRI). Importantly, targeting mitophagy to regulate RCD has shown excellent therapeutic potential in preclinical trials, and is expected to be an effective strategy for the treatment of related diseases. Here, we present a summary of the role of mitophagy in different forms of RCD, with a focus on potential molecular mechanisms by which mitophagy regulates RCD. We also discuss the implications of mitophagy-related RCD in the context of various diseases.


Assuntos
Mitofagia , Humanos , Animais , Morte Celular Regulada , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/genética , Neoplasias/metabolismo , Neoplasias/patologia , Neoplasias/genética
4.
PeerJ Comput Sci ; 10: e2141, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38983203

RESUMO

The reinforcement learning based hyper-heuristics (RL-HH) is a popular trend in the field of optimization. RL-HH combines the global search ability of hyper-heuristics (HH) with the learning ability of reinforcement learning (RL). This synergy allows the agent to dynamically adjust its own strategy, leading to a gradual optimization of the solution. Existing researches have shown the effectiveness of RL-HH in solving complex real-world problems. However, a comprehensive introduction and summary of the RL-HH field is still blank. This research reviews currently existing RL-HHs and presents a general framework for RL-HHs. This article categorizes the type of algorithms into two categories: value-based reinforcement learning hyper-heuristics and policy-based reinforcement learning hyper-heuristics. Typical algorithms in each category are summarized and described in detail. Finally, the shortcomings in existing researches on RL-HH and future research directions are discussed.

5.
Artigo em Inglês | MEDLINE | ID: mdl-38996865

RESUMO

HYPOTHESIS: Our study investigates the reliability of deltoid tuberosity index (DTI) and DTI as a predictor of systemic osteoporosis. BACKGROUND: The proximal humerus is a common fragility fracture. Current literature suggests that poor local bone density is a significant predictor for surgical fixation failure. The DTI is a simple radiographical tool that is strongly correlates with local humeral BMD aiding surgical planning to consider adjuncts or arthroplasty. However, there is a lack of data in the reliability of assessment of DTI, as well as its correlation to systemic osteoporosis. METHODS: Respective cohort of patients with PHF treated at a trauma center in Singapore from August 2017 to July 2018 were recruited. Four raters at different levels of varying clinical seniority measured DTI using shoulder radiographs. The dual energy X-ray Absorptiometry (DEXA) bone mineral density (BMD) scan of the hip and lumbar spine was used to diagnose osteoporosis. Area under receiver operating characteristics (AUROC) analysis was conducted to study the diagnostic utility of DTI to predict the risk of osteoporosis. RESULTS: Our study had 87 patients consisting 18 males and 69 females, mainly of Chinese ethnicity (84%) and mean age of 69.7 years (SD 9.52, range 39-92yrs). For assessment of DTI, there was good intra-rater reliability amongst four raters (correlation coefficient range 0.805- 0.843) and excellent inter-rater reliability between al raters (intraclass correlation coefficient = 0.898; 95% CI 0.784-0.950, p-value <0.001). Based on BMD, 55.2% (n=48) were osteoporotic using T-score <-2.5. The highest correlation of DTI to BMD was with femoral neck density at 0.580. The DTI cut-off of 1.6 had the highest combined sensitivity and false positive rate, with area under curve (AUC) = 0.682 (95% CI, 0.564-0.799) for the overall population and AUC =0.706 (95% CI, 0.569-0.842) for patients <75 years. DISCUSSION: The DTI is a simple and reliable tool, strengthening its applicability in clinical practice to enhance preoperative planning in the surgical fixation of PHF. DTI with a cut off of 1.6 may be helpful tool prompting clinicians to workup and manage underlying osteoporosis.

6.
ESC Heart Fail ; 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39054757

RESUMO

AIMS: We aim to investigate the causal effect of blood lipids mediating sodium-glucose cotransporter 2 (SGLT2) inhibition in cardiovascular disease (CVD) using Mendelian randomization (MR). METHODS AND RESULTS: A two-sample two-step MR study was conducted to evaluate the association of SGLT2 inhibition with CVDs and the mediation effects of blood lipids linking SGLT2 inhibition with CVDs. Genetic instruments for SGLT2 inhibition were identified as genetic variants, which were associated with the expression of the SLC5A2 gene and glycated haemoglobin level (HbA1c). SGLT2 inhibition was associated with reduced risk of heart failure (HF) (OR 0.44 [95% CI 0.32-0.61]; P = 6.0 × 10-7), atrial fibrillation (AF) (0.47 [0.37-0.61]; P = 1.81 × 10-8), coronary artery disease (CAD) (0.47 [0.30-0.73]; P = 7.46 × 10-4), myocardial infarction (MI) (0.30 [0.15-0.61]; P = 7.44 × 10-4), any stroke (AS) (0.28 [0.18-0.42]; P = 1.14 × 10-9), and ischaemic stroke (IS) (0.27 [0.17-0.44]; P = 1.97 × 10-7). Our results indicated that the proportion mediated of the mediating effect of total cholesterol was 1.7% (OR 0.99 [95% CI 0.98, 0.99], P = 0.004), 4.7% (0.96 [0.95, 0.98], P = 0.002), and 2.7% (0.97 [0.95, 0.98], P = 0.002) in the association between SGLT2 inhibition and the risk of HF, CAD, and MI, respectively. For low-density lipoprotein cholesterol, the proportion mediated of the mediating effect was 2.2% for HF (OR 0.98 [95% CI 0.98, 0.99], P = 0.003), 8.6% for CAD (0.93 [0.91, 0.95], P = 5.74 × 10-4), and 5.0% for MI (0.95 [0.94, 0.96], P = 6.97 × 10-4). For non-high-density lipoprotein cholesterol, the proportion mediated of the mediating effect was 3.4% for HF (OR 0.98 [95% CI 0.97, 0.98], P = 4.42 × 10-6), 11.8% for CAD (0.92 [0.90, 0.93], P = 7.23 × 10-8), 5.7% for MI (0.94 [0.92, 0.95], P = 8.17 × 10-7), 1.5% for AS (0.98 [0.98, 0.99], P = 0.001), and 1.4% for IS (0.98 [0.98, 0.99], P = 0.004). CONCLUSIONS: Our study showed the association of SGLT2 inhibition with the reduced risk of CVDs and blood lipids might mediate this association.

7.
Front Cardiovasc Med ; 11: 1410222, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39055661

RESUMO

Background: Aortic stenosis (AS) in combination with left ventricular outflow tract obstruction (LVOTO) has occasionally been reported. However, making a precise diagnosis and successfully treating this combination is challenging due to the hemodynamic interaction between the two conditions. Case summary: A 56-year-old male patient who had been diagnosed with severe AS and asymmetric left ventricular hypertrophy underwent aortic valve replacement (AVR) and a conventional septal myectomy. Immediately after the procedure, significant systolic anterior motion and mitral regurgitation developed, necessitating a surgical mitral edge-to-edge repair. Ten days after the procedure, the patient developed hematuria and LVOTO, which was confirmed by echocardiography. Because the LVOTO might have been the cause of the hematuria, the patient underwent alcohol septal ablation, but this had little effect. Three months later, a transapical beating-heart septal myectomy (TA-BSM) was performed in our hospital. Postoperatively, the LVOTO had been significantly ameliorated and the hematuria had resolved. Conclusion: For patients with AS and LVOTO due to a hypertrophic interventricular septum, inadequate amelioration of the LVOTO after AVR may lead to severe hemolytic hematuria. TA-BSM is a minimally invasive, safe, and effective surgical procedure for ameliorating LVOTO in patients with aortic valve prostheses.

8.
Trends Pharmacol Sci ; 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-39003157

RESUMO

PANoptosis is a unique innate immune inflammatory lytic cell death pathway initiated by an innate immune sensor and driven by caspases and RIPKs. As a distinct pathway, the execution of PANoptosis cannot be hindered by targeting other cell death pathways, such as pyroptosis, apoptosis, or necroptosis. Instead, targeting key PANoptosome components can serve as a strategy to prevent this form of cell death. Given the physiological relevance in several diseases, PANoptosis is a pivotal therapeutic target. Notably, previous research has primarily focused on the role of PANoptosis in cancer and infectious and inflammatory diseases. By contrast, its role in cardiovascular diseases has not been comprehensively discussed. Here, we review the available evidence on PANoptosis in cardiovascular diseases, including cardiomyopathy, atherosclerosis, myocardial infarction, myocarditis, and aortic aneurysm and dissection, and explore a variety of agents that target PANoptosis, with the overarching goal of providing a novel complementary approach to combatting cardiovascular diseases.

9.
Prenat Diagn ; 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39030774

RESUMO

OBJECTIVE: This study aimed to evaluate the yield and applicability of expanded carrier screening and propose carrier rate screening thresholds suitable for the Chinese population by comparing the current screening panel with the American College of Medical Genetics and Genomics recommended panel of 113 genes. METHODS: Using targeted next-generation sequencing, a customized panel with 334 genes was performed on 2168 individuals without clinical phenotypes for expanded carrier screening purpose. Variant interpretation followed the American College of Medical Genetics and Genomics guidelines. Carrier rates were calculated for each identified variant and each gene. At-risk couple rates were also assessed. The yield of expanded carrier screening was evaluated through calculating cumulative carrier rate. RESULTS: Overall, 65.87% of the individuals were found to be carriers of at least 1 disease causing variants. The overall at-risk couple rate was 11.76%, of which the GJB2:c.109G > A related at-risk couple rate was 5.78%. The cumulative carrier rate of 334-panel was 65.53%. When screened genes with gene carrier rate ≥1/1000, the expanded carrier screening can cover over 90% of the cumulative carrier rate and at-risk couples. A total of 86 genes overlapped with American College of Medical Genetics and Genomics Tier-3 genes and were attributed to the cumulative carrier rate of 47.33%. CONCLUSION: Expanded carrier screening using the 334-gene panel showed high screening efficiency. A threshold of gene carrier rate ≥1/1000 is recommended for selecting carrier screening genes in the Chinese Han population. This study highlights the importance of customizing screening panels based on the ACMG Tier-3 genes in conjunction with population-specific carrier frequencies to improve the accuracy and effectiveness of expanded carrier screening.

10.
Heliyon ; 10(13): e33614, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39040292

RESUMO

Ex vivo lung perfusion (EVLP) is a promising technology that allows the re-evaluation of donor lungs and has the potential to improve marginal lung reconditioning. The present study focused on the effects of milk fat globule epidermal growth factor 8 (MFG-E8) on the function of donation after circulatory death (DCD) lungs during EVLP and transplant reperfusion. Domestic swine were assigned to 4 groups. In the control group, the donor lungs lacking warm ischemia were preserved in Perfadex for 4 h. The swine in the other three groups underwent hypoxic arrest, followed by 1 h of warm ischemia. The DCD lungs were procured and randomly divided into three groups: cold static preservation (DCD-CSP) group, DCD-EVLP group, and DCD-MFG-E8 group. The left lung of all groups was transplanted and reperfused. During EVLP and reperfusion, lung functions and pathological evaluations were performed. Treatment with MFG-E8 resulted in significantly improved blood oxygenation. The mean pulmonary artery pressure, peak airway pressure, and expression of IL-1ß, IL-6, and IL-12 were significantly lower but IL-10 was higher in the DCD -MFG-E8 group. Furthermore, the lung injury severity score, pulmonary edema, and wet-to-dry weight ratio were also reduced in MFG-E8-treated lungs. However, the pulmonary vascular resistance and expression of TNF-α did not differ from the DCD -EVLP group but were significantly lower than in the DCD -CSP group. Adding MFG-E8 into the perfusate during EVLP obtains optimal graft function of lungs from DCD. This finding, if confirmed clinically, can be applied to recondition grafts and expanded use of DCD lungs.

11.
Nat Biomed Eng ; 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38834752

RESUMO

The manufacturing of autologous chimaeric antigen receptor (CAR) T cells largely relies either on fed-batch and manual processes that often lack environmental monitoring and control or on bioreactors that cannot be easily scaled out to meet patient demands. Here we show that human primary T cells can be activated, transduced and expanded to high densities in a 2 ml automated closed-system microfluidic bioreactor to produce viable anti-CD19 CAR T cells (specifically, more than 60 million CAR T cells from donor cells derived from patients with lymphoma and more than 200 million CAR T cells from healthy donors). The in vitro secretion of cytokines, the short-term cytotoxic activity and the long-term persistence and proliferation of the cell products, as well as their in vivo anti-leukaemic activity, were comparable to those of T cells produced in a gas-permeable well. The manufacturing-process intensification enabled by the miniaturized perfusable bioreactor may facilitate the analysis of the growth and metabolic states of CAR T cells during ex vivo culture, the high-throughput optimization of cell-manufacturing processes and the scale out of cell-therapy manufacturing.

12.
Int J Biol Sci ; 20(8): 2904-2921, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38904023

RESUMO

Abnormal proliferation of pulmonary artery smooth muscle cells (PASMCs) is one of the critical pathological mechanisms of pulmonary hypertension (PH), and therefore is gradually being adopted as an important direction for the treatment of PH. Metallothioneins (MTs) have been reported to be associated with PH, but the underlying mechanisms are not fully understood. Here, we demonstrated that the expression level of metallothionein 3 (MT3) was significantly increased in pulmonary arterioles from PH patients and chronic hypoxia-induced rat and mouse PH models, as well as in hypoxia-treated human PASMCs. Knockdown of MT3 significantly inhibited the proliferation of human PASMCs by arresting the cell cycle in the G1 phase, while overexpression of MT3 had the opposite effect. Mechanistically, we found that MT3 increased the intracellular zinc (Zn2+) concentration to enhance the transcriptional activity of metal-regulated transcription factor 1 (MTF1), which promoted the expression of autophagy-related gene 5 (ATG5), facilitating autophagosome formation. More importantly, MT3-induced autophagy and proliferation of human PASMCs were largely prevented by knockdown of MTF1 and ATG5. Therefore, in this study, we identified MT3-Zinc-MTF1-ATG5 as a novel pathway that affects PASMC proliferation by regulating autophagosome formation, suggesting that MT3 may be a novel target for the treatment of PH.


Assuntos
Proliferação de Células , Metalotioneína 3 , Miócitos de Músculo Liso , Artéria Pulmonar , Zinco , Artéria Pulmonar/citologia , Artéria Pulmonar/metabolismo , Animais , Humanos , Zinco/metabolismo , Camundongos , Ratos , Miócitos de Músculo Liso/metabolismo , Masculino , Autofagossomos/metabolismo , Proteína 5 Relacionada à Autofagia/metabolismo , Proteína 5 Relacionada à Autofagia/genética , Ratos Sprague-Dawley , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Autofagia , Hipertensão Pulmonar/metabolismo , Camundongos Endogâmicos C57BL , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Fator MTF-1 de Transcrição , Metalotioneína/metabolismo , Metalotioneína/genética
13.
CNS Neurosci Ther ; 30(6): e14792, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38867393

RESUMO

AIMS: Parkinson's disease (PD) patients experience improvement in motor symptoms after deep brain stimulation (DBS) and before initiating stimulation. This is called the microlesion effect. However, the mechanism remains unclear. The study aims to comprehensively explore the changes in functional connectivity (FC) patterns in movement-related brain regions in PD patients during the microlesion phase through seed-based FC analysis. METHODS: The study collected the resting functional magnetic resonance imaging data of 49 PD patients before and after DBS surgery (off stimulation). The cortical and subcortical areas related to motor function were selected for seed-based FC analysis. Meanwhile, their relationship with the motor scale was investigated. RESULTS: The motor-related brain regions were selected as the seed point, and we observed various FC declines within the motor network brain regions. These declines were primarily in the left middle temporal gyrus, bilateral middle frontal gyrus, right supplementary motor area, left precentral gyrus, left postcentral gyrus, left inferior frontal gyrus, and right superior frontal gyrus after DBS. CONCLUSION: The movement-related network was extensively reorganized during the microlesion period. The study provided new information on enhancing motor function from the network level post-DBS.


Assuntos
Estimulação Encefálica Profunda , Imageamento por Ressonância Magnética , Doença de Parkinson , Humanos , Estimulação Encefálica Profunda/métodos , Doença de Parkinson/terapia , Doença de Parkinson/fisiopatologia , Doença de Parkinson/diagnóstico por imagem , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Córtex Motor/fisiopatologia , Córtex Motor/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia
14.
Circ Res ; 135(1): 93-109, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38770649

RESUMO

BACKGROUND: Hyperproliferation of pulmonary arterial smooth muscle cells (PASMCs) and consequent pulmonary vascular remodeling are the crucial pathological features of pulmonary hypertension (PH). Protein methylation has been shown to be critically involved in PASMC proliferation and PH, but the underlying mechanism remains largely unknown. METHODS: PH animal models were generated by treating mice/rats with chronic hypoxia for 4 weeks. SMYD2-vTg mice (vascular smooth muscle cell-specific suppressor of variegation, enhancer of zeste, trithorax and myeloid Nervy DEAF-1 (deformed epidural auto-regulatory factor-1) domain-containing protein 2 transgenic) or wild-type rats and mice treated with LLY-507 (3-cyano-5-{2-[4-[2-(3-methylindol-1-yl)ethyl]piperazin-1-yl]-phenyl}-N-[(3-pyrrolidin-1-yl)propyl]benzamide) were used to investigate the function of SMYD2 (suppressor of variegation, enhancer of zeste, trithorax and myeloid Nervy DEAF-1 domain-containing protein 2) on PH development in vivo. Primary cultured rat PASMCs with SMYD2 knockdown or overexpression were used to explore the effects of SMYD2 on proliferation and to decipher the underlying mechanism. RESULTS: We demonstrated that the expression of the lysine methyltransferase SMYD2 was upregulated in the smooth muscle cells of pulmonary arteries from patients with PH and hypoxia-exposed rats/mice and in the cytoplasm of hypoxia-induced rat PASMCs. More importantly, targeted inhibition of SMYD2 by LLY-507 significantly attenuated hypoxia-induced pulmonary vascular remodeling and PH development in both male and female rats in vivo and reduced rat PASMC hyperproliferation in vitro. In contrast, SMYD2-vTg mice exhibited more severe PH phenotypes and related pathological changes than nontransgenic mice after 4 weeks of chronic hypoxia treatment. Furthermore, SMYD2 overexpression promoted, while SMYD2 knockdown suppressed, the proliferation of rat PASMCs by affecting the cell cycle checkpoint between S and G2 phases. Mechanistically, we revealed that SMYD2 directly interacted with and monomethylated PPARγ (peroxisome proliferator-activated receptor gamma) to inhibit the nuclear translocation and transcriptional activity of PPARγ, which further promoted mitophagy to facilitate PASMC proliferation and PH development. Furthermore, rosiglitazone, a PPARγ agonist, largely abolished the detrimental effects of SMYD2 overexpression on PASMC proliferation and PH. CONCLUSIONS: Our results demonstrated that SMYD2 monomethylates nonhistone PPARγ and inhibits its nuclear translocation and activation to accelerate PASMC proliferation and PH by triggering mitophagy, indicating that targeting SMYD2 or activating PPARγ are potential strategies for the prevention of PH.


Assuntos
Histona-Lisina N-Metiltransferase , Hipertensão Pulmonar , Hipóxia , Mitofagia , Músculo Liso Vascular , Miócitos de Músculo Liso , PPAR gama , Artéria Pulmonar , Ratos Sprague-Dawley , Animais , Humanos , Masculino , Camundongos , Ratos , Proliferação de Células , Células Cultivadas , Histona-Lisina N-Metiltransferase/metabolismo , Histona-Lisina N-Metiltransferase/genética , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/patologia , Hipertensão Pulmonar/genética , Hipóxia/complicações , Hipóxia/metabolismo , Metilação , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , PPAR gama/metabolismo , Artéria Pulmonar/patologia , Artéria Pulmonar/metabolismo , Remodelação Vascular
15.
Light Sci Appl ; 13(1): 104, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38710692

RESUMO

A highly homogeneous microwave zero-index metamaterial based on high-permittivity SrTiO3 ceramics is demonstrated to realize the small-aperture high-directivity antenna. Such a novel technique is a remarkable step forward to develop compact devices with better performance.

16.
Signal Transduct Target Ther ; 9(1): 135, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38760366

RESUMO

DNA double-strand break (DSB) sites that prevent the disjunction of broken DNA ends are formed through poly (ADP-ribose) (PAR) polymerase 1 (PARP1)-DNA co-condensation. The co-condensates apply mechanical forces to hold the DNA ends together and generate enzymatic activity for the synthesis of PAR. PARylation can promote the release of PARP1 from DNA ends and recruit various proteins, such as Fused in sarcoma (FUS) proteins, thereby stabilizing broken DNA ends and preventing their separation.


Assuntos
Quebras de DNA de Cadeia Dupla , Reparo do DNA , DNA , Poli(ADP-Ribose) Polimerase-1 , Humanos , Poli(ADP-Ribose) Polimerase-1/genética , Poli(ADP-Ribose) Polimerase-1/metabolismo , Reparo do DNA/genética , DNA/genética , DNA/metabolismo
17.
Heliyon ; 10(10): e31492, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38807870

RESUMO

Background: We developed a novel minimally invasive transapical beating-heart septal myectomy (TA-BSM) procedure for patients with midventricular obstruction (MVO), without the aid of cardiopulmonary bypass. This study aims to describe the TA-BSM procedure for the relief of MVO and to detail the clinical outcomes in these patients. Methods: Sixty-one patients receiving TA-BSM for MVO were included: isolated MVO (n = 12) and combined MVO and subaortic obstruction (n = 49). We reviewed the electronic medical record to collect information on preoperative, intraoperative, and postoperative parameters. Results: The intraventricular pressure gradient after the resection was largely attenuated. On the catheter measurement, the median resting and provoked gradient decreased by 29.0 and 71.0 mm Hg, respectively. Likewise, the resting intraventricular gradient was successfully reduced from 58.0 to 11.0 mm Hg, and the maximal intraventricular gradient was reduced from 88.0 to 20.0 mm Hg at 6 months follow-up. In addition, all patients showed significantly improved MR and 37 of 42 patients with preoperative MR grade ≥2+ showed MR grade ≤1+ after TA-BSM. During the follow-up, no death was observed and no one had HCM-related rehospitalization. All patients reported improvement in symptoms and the mean New York Heart Association class improved from 3.0 (IQR, 3.0-3.0) preoperatively to 1.0 (IQR, 1.0-1.0) at 6 months follow-up. Conclusions: The TA-BSM procedure is a valuable therapy to relieve MVO, improving hemodynamics and providing satisfactory clinical outcomes. The procedure can also preserve favorable outcomes for patients with MVO and concomitant subaortic obstruction.

18.
Heliyon ; 10(9): e29350, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38694110

RESUMO

Objectives: This study aimed to explore the spatial distribution of brain metastases (BMs) from breast cancer (BC) and to identify the high-risk sub-structures in BMs that are involved at first diagnosis. Methods: Magnetic resonance imaging (MRI) scans were retrospectively reviewed at our centre. The brain was divided into eight regions according to its anatomy and function, and the volume of each region was calculated. The identification and volume calculation of metastatic brain lesions were accomplished using an automatically segmented 3D BUC-Net model. The observed and expected rates of BMs were compared using 2-tailed proportional hypothesis testing. Results: A total of 250 patients with BC who presented with 1694 BMs were retrospectively identified. The overall observed incidences of the substructures were as follows: cerebellum, 42.1 %; frontal lobe, 20.1 %; occipital lobe, 9.7 %; temporal lobe, 8.0 %; parietal lobe, 13.1 %; thalamus, 4.7 %; brainstem, 0.9 %; and hippocampus, 1.3 %. Compared with the expected rate based on the volume of different brain regions, the cerebellum, occipital lobe, and thalamus were identified as higher risk regions for BMs (P value ≤ 5.6*10-3). Sub-group analysis according to the type of BC indicated that patients with triple-negative BC had a high risk of involvement of the hippocampus and brainstem. Conclusions: Among patients with BC, the cerebellum, occipital lobe and thalamus were identified as higher-risk regions than expected for BMs. The brainstem and hippocampus were high-risk areas of the BMs in triple negative breast cancer. However, further validation of this conclusion requires a larger sample size.

19.
Medicine (Baltimore) ; 103(14): e36823, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38579055

RESUMO

BACKGROUND: Postherpetic neuralgia (PHN) is the most common complication of varicella-zoster infection and tends to occur in older people. All patients treated with a single regimen have not achieved consistent success across all current study protocols, and multimodal combination regimens still need to be explored. METHODS: A total of 111 patients with PHN were randomly divided into drug group (group A), thoracic paravertebral nerve block group (group B), thoracic paravertebral nerve block combined with acupuncture group (group C), with 37 cases in each group. Group A: received oral gabapentin capsules and external lidocaine gel plaster; group B: combined with thoracic paravertebral nerve block based on group A; group C: combined with acupuncture based on group B. The primary outcome was effective rate, and secondary outcomes included pain sensation score (numerical rating scale), SF-36 quality of life score, and sleep quality. RESULTS: Before treatment, there were no significant differences in numerical rating scale value, SF-36 quality of life score, and sleep quality level among the 3 groups (P > .05). After 12 weeks of treatment, the total effective rate of treatment of patients in group C (91.43%) was higher than that in group B (77.14%), and significantly higher than that in group A (51.43%) (P < .05). CONCLUSION: Based on drug treatment combined with thoracic paravertebral nerve block and acupuncture, the treatment of PHN in the elderly can quickly and effectively relieve pain, improve the quality of life of patients, and improve the quality of sleep.


Assuntos
Terapia por Acupuntura , Bloqueio Nervoso , Neuralgia Pós-Herpética , Humanos , Idoso , Neuralgia Pós-Herpética/tratamento farmacológico , Qualidade de Vida , Estudos Prospectivos , Bloqueio Nervoso/métodos , Abdome
20.
Heliyon ; 10(8): e29158, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38644876

RESUMO

Objective: To establish a predictive modeling for the risk of bloodstream infection associated with peripherally inserted central catheter (PICC). Methods: Patients receiving PICC treatment in Shenzhen People's Hospital from June 2020 to December 2020 were retrospectively enrolled and divided into the infection group and the non-infection group according to the presence and absence of PICC-related infections. Then, relevant clinical information of patients was collected and the predictors of PICC-related infection were screened by the least absolute shrinkage and selection operator regression (LASSO) model. Besides, multivariate logistic regression was used to analyze the influencing factors of PICC-related infection, A nomogram was constructed based on the results of the multivariate analysis. Ultimately, a receiver operating characteristic (ROC) curve was plotted to analyze the application value of influencing factors to predict PICC-related infections. Results: A total of 505 patients were included, including 75 patients with PICC-related infections (14.85%). The main pathogen was gram-positive cocci. The predictors screened by LASSO included age >60 years, catheter movement, catheter maintenance cycle, insertion technique, immune function, complications, and body temperature ≥37.2 °C before PICC placement. Multivariate logistic regression analysis showed that independent risk factors of infections related to PICC included age >60 years [odds ratio (OR) = 1.722; 95% confidence interval (CI) = 1.312-3.579; P = 0.006], catheter movement (OR = 1.313; 95% CI = 1.119-3.240; P = 0.014), catheter maintenance cycle >7 days (OR = 2.199; 95% CI = 1.677-4.653; P = 0.000), direct insertion (OR = 1.036; 95% CI = 1.019-2.743; P = 0.000), poor immune function (OR = 2.322; 95% CI = 2.012-4.579; P = 0.000), complications (OR = 1.611; 95% CI = 1.133-3.454; P = 0.019), and body temperature ≥37.2 °C before PICC placement (OR = 1.713; 95% CI = 1.172-3.654; P = 0.012). Besides, the area under the ROC curve was 0.889. Conclusion: PICC-related infections are associated with factors such as age >60 years, catheter movement, catheter maintenance cycle, insertion technique, immune function, complications, and body temperature ≥37.2 °C before PICC placement. Additionally, the LASSO model is moderately predictive for predicting the occurrence of PICC-related infections.

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