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Korean Circulation Journal Jun 2024Although the clinical consequences of advanced heart failure (HF) may be similar across different etiologies of cardiomyopathies, their proteomic expression may show...
BACKGROUND AND OBJECTIVES
Although the clinical consequences of advanced heart failure (HF) may be similar across different etiologies of cardiomyopathies, their proteomic expression may show substantial differences in relation to underlying pathophysiology. We aimed to identify myocardial tissue-based proteomic characteristics and the underlying molecular pathophysiology in non-ischemic cardiomyopathy with different etiologies.
METHODS
Comparative extensive proteomic analysis of the myocardium was performed in nine patients with biopsy-proven non-ischemic cardiomyopathies (3 dilated cardiomyopathy [DCM], 2 hypertrophic cardiomyopathy [HCM], and 4 myocarditis) as well as five controls using tandem mass tags combined with liquid chromatography-mass spectrometry. Differential protein expression analysis, Gene Ontology (GO) analysis, and Ingenuity Pathway Analysis (IPA) were performed to identify proteomic differences and molecular mechanisms in each cardiomyopathy type compared to the control. Proteomic characteristics were further evaluated in accordance with clinical and pathological findings.
RESULTS
The principal component analysis score plot showed that the controls, DCM, and HCM clustered well. However, myocarditis samples exhibited scattered distribution. IPA revealed the downregulation of oxidative phosphorylation and upregulation of the sirtuin signaling pathway in both DCM and HCM. Various inflammatory pathways were upregulated in myocarditis with the downregulation of Rho GDP dissociation inhibitors. The molecular pathophysiology identified by extensive proteomic analysis represented the clinical and pathological properties of each cardiomyopathy with abundant proteomes.
CONCLUSIONS
Different etiologies of non-ischemic cardiomyopathies in advanced HF exhibit distinct proteomic expression despite shared pathologic findings. The benefit of tailored management strategies considering the different proteomic expressions in non-ischemic advanced HF requires further investigation.
PubMed: 38956938
DOI: 10.4070/kcj.2024.0033 -
BMC Veterinary Research Jul 2024The red panda is currently the only surviving member of the Ailuridae family in the Caniformia suborder. In this study, we provide data on anatomical, morphometric,...
OBJECTIVES
The red panda is currently the only surviving member of the Ailuridae family in the Caniformia suborder. In this study, we provide data on anatomical, morphometric, histological and histochemical examination of the orbital region, eyelids, orbital gland, and eye tunics in two adult males Ailurus fulgens fulgens from the Wroclaw Zoological Garden, Poland.
METHODS
The study involved morphometric analysis of the eyeball and selected accessory organs of the eye, along with analysis of the bony orbit, including its morphometry, macroscopic, and microscopic evaluation. Microscopic evaluation encompassed histological and histochemical staining, with the former involving hematoxylin & eosin (H&E), Movat pentachrome, picro-Mallory trichrome, Fontana-Masson, and the latter including PAS, AB pH 1.0, AB pH 2.5; AB pH 2.5/PAS, and HDI.
RESULTS
The upper (UE) and lower (LE) eyelids presented well-developed tarsal glands, sebaceous glands, and a characteristic simple alveolar gland (producing a mucous secretion). The palpebral part of the lacrimal gland was present. A single lymphoid follicle was observed only in the upper eyelids. The superficial gland of the third eyelid (SGTE) was a multilobar acinar complex that produces mucous secretion and is contained within the interlobular ducts of numerous aggregates of lymph nodes. The third eyelid (TE) was T-shaped and composed of hyaline tissue, containing CALT. The lacrimal gland (LG) also revealed a multilobar acinar complex that produced mucous secretion, with a single lymphoid follicle. The cornea consisted of 4 layers, as Bowman's membrane was absent. The Vogt palisades composed of 7-10 layers of epithelial cells were demonstrated. The pupil was horizontally ovoid at rest (post-mortem). The sphincter pupil and the dilator pupil were well developed. Macroscopically, the tapetum lucidum appeared as a milky, non-opalescent crescent. Histologically, the choroidal tapetum lucidum cellulosum consisted of 5 to 9 layers of loosely packed oval cells. The retina showed a composition similar to that of terrestrial nocturnal carnivores.
CONCLUSIONS
The results of our research indicate that the anatomical features of the eye and orbital region in the red panda share similarities with those described in the Musteloidea clade, as well as the Canidae and Ursidae families.
Topics: Animals; Male; Ailuridae; Orbit; Eye; Eyelids
PubMed: 38956555
DOI: 10.1186/s12917-024-04152-2 -
Scientific Reports Jul 2024Detecting and replacing defective photovoltaic modules is essential as they directly impact power generation efficiency. Many current deep learning-based methods for...
Detecting and replacing defective photovoltaic modules is essential as they directly impact power generation efficiency. Many current deep learning-based methods for detecting defects in photovoltaic modules focus solely on either detection speed or accuracy, which limits their practical application. To address this issue, an improved VarifocalNet has been proposed to enhance both the detection speed and accuracy of defective photovoltaic modules. Firstly, a new bottleneck module is designed to replace the first bottleneck module of the last stage convolution group in the backbone. This new module includes both standard convolution and dilated convolution, enabling an increase in network depth and receptive field without reducing the output feature map size. This improvement can help to enhance the accuracy of defect detection for photovoltaic modules. Secondly, another bottleneck module is also designed and used to replace the original bottleneck module used in the fourth stage convolution group of the backbone. This new module has smaller parameters than the original bottleneck module, which is useful to improve the defect detection speed of the photovoltaic module. Thirdly, a feature interactor is designed in the detection head to enhance feature expression in the classification branch. This helps improve detection accuracy. Besides, an improved intersection over union is proposed and introduced into the loss function to measure the difference between the predicted and ground truth boxes. This is useful for improving defect detection accuracy. Compared to other methods, the proposed method has the highest detection accuracy. Additionally, it also has a faster detection speed than other methods except for the DDH-YOLOv5 method and the improved YOLOv7 method.
PubMed: 38956270
DOI: 10.1038/s41598-024-66234-3 -
CMAJ : Canadian Medical Association... Jul 2024
PubMed: 38955415
DOI: 10.1503/cmaj.240833 -
Cell Reports Jun 2024Cell functions rely on intracellular transport systems distributing bioactive molecules with high spatiotemporal accuracy. The endoplasmic reticulum (ER) tubular network...
Cell functions rely on intracellular transport systems distributing bioactive molecules with high spatiotemporal accuracy. The endoplasmic reticulum (ER) tubular network constitutes a system for delivering luminal solutes, including Ca, across the cell periphery. How the ER structure enables this nanofluidic transport system is unclear. Here, we show that ER membrane-localized reticulon 4 (RTN4/Nogo) is sufficient to impose neurite outgrowth inhibition in human cortical neurons while acting as an ER morphoregulator. Improving ER transport visualization methodologies combined with optogenetic Ca dynamics imaging and in silico modeling, we observed that ER luminal transport is modulated by ER tubule narrowing and dilation, proportional to the amount of RTN4. Excess RTN4 limited ER luminal transport and Ca release, while RTN4 elimination reversed the effects. The described morphoregulatory effect of RTN4 defines the capacity of the ER for peripheral Ca delivery for physiological releases and thus may constitute a mechanism for controlling the (re)generation of neurites.
PubMed: 38955182
DOI: 10.1016/j.celrep.2024.114357 -
PloS One 2024Bicuspid aortic valves (BAV) are frequently associated with ascending aortic aneurysms. The etiology is incompletely understood, but genetic factors, in addition to flow...
BACKGROUND
Bicuspid aortic valves (BAV) are frequently associated with ascending aortic aneurysms. The etiology is incompletely understood, but genetic factors, in addition to flow perturbations, are likely involved. Since loss of contractility and elaboration of extracellular matrix in the vessel wall are features of BAV-associated aortopathy, phenotypic modulation of smooth muscle cells (SMCs) may play a role.
METHODS
Ascending aortic tissue was collected intra-operatively from 25 individuals with normal (i.e., tricuspid) aortic valves (TAV) and from 25 individuals with BAVs. For both TAV and BAV, 10 patients had non-dilated (ND) and 15 patients had dilated (D) aortas. SMCs were isolated and cultured from a subset of patients from each group. Aortic tissue and SMCs were fluorescently immunolabeled for SMC phenotypic markers (i.e., alpha-smooth muscle actin (ASMA, contractile), vimentin (synthetic) and p16INK4a and p21Cip1 (senescence). SMCs were also analyzed for replicative senescence in culture.
RESULTS
In normal-sized and dilated BAV aortas, SMCs switched from the contractile state to either synthetic or senescent phenotypes, as observed by loss of ASMA (ND: P = 0.001, D: P = 0.002) and associated increases in vimentin (ND: P = 0.03, D: P = 0.004) or p16/p21 (ND: P = 0.03, D: P<0.0001) compared to TAV. Dilatation of the aorta exacerbated SMC phenotypic switching in both BAV and TAV aortas (all P<0.05). In SMCs cultured from normal and dilated aortas, those isolated from BAV reached replicative senescence faster than those from TAV aortas (all P = 0.02). Furthermore, there was a stark inverse correlation between ASMA and cell passage number in BAV SMCs (ND: P = 0.0006, D: P = 0.01), but not in TAV SMCs (ND: P = 0.93, D: P = 0.20).
CONCLUSIONS
The findings of this study provide direct evidence from cell culture studies implying that SMCs switch from the contractile state to either synthetic or senescent phenotypes in the non-dilated BAV aorta. In cultured SMCs from both non-dilated and dilated aortas, we found that this process may precede dilatation and accompany aneurysm development in BAV. Our findings suggest that therapeutically targeting SMC phenotypic modulation in BAV patients may be a viable option to prevent or delay ascending aortic aneurysm formation.
Topics: Humans; Aortic Valve; Bicuspid Aortic Valve Disease; Myocytes, Smooth Muscle; Heart Valve Diseases; Aorta; Male; Middle Aged; Phenotype; Female; Dilatation, Pathologic; Adult; Cellular Senescence; Cells, Cultured; Aged; Actins; Aortic Aneurysm; Vimentin
PubMed: 38954721
DOI: 10.1371/journal.pone.0306515 -
Current Urology Reports Jul 2024To review and describe the recent evolution of surgery for the various types of pediatric megaureter. (Review)
Review
PURPOSE OF REVIEW
To review and describe the recent evolution of surgery for the various types of pediatric megaureter.
RECENT FINDINGS
Megaureter management first relies on determining the underlying cause, whether by obstruction, reflux, or a combination, and then setting appropriate surgical indications because many cases do not require surgery as shown by observation studies. Endoscopic balloon dilation has been on the rise as a major treatment option for obstructive megaureter, while refluxing megaureters can also be treated by laparoscopic and robotic techniques, whether extravesically or transvesicoscopically. During ureteral reimplantation, tapering is sometimes necessary to address the enlarged ureter, but there are also considerations for not tapering or for tapering alternatives. Endoscopic and minimally invasive surgeries for megaureter have been the predominant focus of recent megaureter literature. These techniques still need collaborative prospective studies to better define which surgeries are best for patients needing megaureter interventions.
PubMed: 38954357
DOI: 10.1007/s11934-024-01214-8 -
Archives of Gynecology and Obstetrics Jul 2024
PubMed: 38953976
DOI: 10.1007/s00404-024-07606-y -
Small (Weinheim An Der Bergstrasse,... Jul 2024Abdominal aortic aneurysm (AAA) represents a critical cardiovascular condition characterized by localized dilation of the abdominal aorta, carrying a significant risk of...
Abdominal aortic aneurysm (AAA) represents a critical cardiovascular condition characterized by localized dilation of the abdominal aorta, carrying a significant risk of rupture and mortality. Current treatment options are limited, necessitating novel therapeutic approaches. This study investigates the potential of a pioneering nanodrug delivery system, RAP@PFB, in mitigating AAA progression. RAP@PFB integrates pentagalloyl glucose (PGG) and rapamycin (RAP) within a metal-organic-framework (MOF) structure through a facile assembly process, ensuring remarkable drug loading capacity and colloidal stability. The synergistic effects of PGG, a polyphenolic antioxidant, and RAP, an mTOR inhibitor, collectively regulate key players in AAA pathogenesis, such as macrophages and smooth muscle cells (SMCs). In macrophages, RAP@PFB efficiently scavenges various free radicals, suppresses inflammation, and promotes M1-to-M2 phenotype repolarization. In SMCs, it inhibits apoptosis and calcification, thereby stabilizing the extracellular matrix and reducing the risk of AAA rupture. Administered intravenously, RAP@PFB exhibits effective accumulation at the AAA site, demonstrating robust efficacy in reducing AAA progression through multiple mechanisms. Moreover, RAP@PFB demonstrates favorable biosafety profiles, supporting its potential translation into clinical applications for AAA therapy.
PubMed: 38953313
DOI: 10.1002/smll.202402141 -
The Journal of Obstetrics and... Jul 2024A 35-year-old woman (gravida 1, para 0) was admitted to our hospital at 28 weeks' gestation with vaginal bleeding from placenta previa. Severe fetal bradycardia was...
A 35-year-old woman (gravida 1, para 0) was admitted to our hospital at 28 weeks' gestation with vaginal bleeding from placenta previa. Severe fetal bradycardia was observed during fetal heart rate monitoring. Ultrasonography showed widely dilated veins on the fetal surface of the placenta and an extraordinarily low umbilical artery peak systolic velocity in the Doppler study. Umbilical cord torsion was suspected. On the subsequent day, we performed a cesarean section due to worsening fetal heart rate patterns. Umbilical artery blood gas analysis indicated severe acidemia (pH 7.063), and umbilical cord torsion was confirmed at the placental cord insertion site. Diagnosing UCT prenatally is challenging; however, it can be suspected by scanning for the widely dilated veins on the fetal placental surface, termed as the "Sunset Sign," an abnormally low umbilical artery peak systolic velocity, and other fetal Doppler abnormalities.
PubMed: 38953213
DOI: 10.1111/jog.16013