Conversely, the NGF administration on H sperm did not change either the percentage of dead cells or the apoptotic rate.

The concentration of p75

on ejaculated sperm modulates many semen outcomes (motility, apoptosis, viability) through NGF interaction affecting the senescence of sperm.

The concentration of p75NTR on ejaculated sperm modulates many semen outcomes (motility, apoptosis, viability) through NGF interaction affecting the senescence of sperm.

To develop a deep-learning (DL) pipeline that allowed an automated segmentation of epicardial adipose tissue (EAT) from low-dose computed tomography (LDCT) and investigate the link between EAT and COVID-19 clinical outcomes.

This monocentric retrospective study included 353 patients 95 for training, 20 for testing, and 238 for prognosis evaluation. EAT segmentation was obtained after thresholding on a manually segmented pericardial volume. The model was evaluated with Dice coefficient (DSC), inter-and intraobserver reproducibility, and clinical measures. Uni-and multi-variate analyzes were conducted to assess the prognosis value of the EAT volume, EAT extent, and lung lesion extent on clinical outcomes, including hospitalization, oxygen therapy, intensive care unit admission and death.

The mean DSC for EAT volumes was 0.85 ± 0.05. For EAT volume, the mean absolute error was 11.7 ± 8.1 cm

with a non-significant bias of -4.0 ± 13.9 cm

and a correlation of 0.963 with the manual measures (

< 0.01). The multivariate model providing the higher AUC to predict adverse outcome include both EAT extent and lung lesion extent (AUC = 0.805).

A DL algorithm was developed and evaluated to obtain reproducible and precise EAT segmentation on LDCT. EAT extent in association with lung lesion extent was associated with adverse clinical outcomes with an AUC = 0.805.

A DL algorithm was developed and evaluated to obtain reproducible and precise EAT segmentation on LDCT. EAT extent in association with lung lesion extent was associated with adverse clinical outcomes with an AUC = 0.805.Many studies have demonstrated significant mouse-strain-specific differences in behavior and response to pathogenic and pharmacological agents. This study seeks to characterize possible differences in microglia activation and overall severity of neuroinflammation in two widely used mouse strains, C57BL/6NTac (Bl6) and 129S6/SvEvTac (129Sv), in response to acute lipopolysaccharide (LPS) administration. Locomotor activity within the open field arena revealed similar 24 h motor activity decline in both strains. Both strains also exhibited significant bodyweight loss due to LPS treatment, although it was more severe in the Bl6 strain. Furthermore, LPS induced a hypothermic response in Bl6 mice, which was not seen in 129Sv. We found that 24 h LPS challenge significantly increased the inflammatory status of microglia in 129Sv mice. On the other hand, we observed that, under physiological conditions, microglia of Bl6 seemed to be in a higher immune-alert state. Gene and protein expression analysis revealed that LPS induces a significantly stronger upregulation of MHC-I-pathway-related components in the brain of Bl6 compared to 129Sv mice. The most striking difference was detected in the olfactory bulb, where we observed significant LPS-induced upregulation of MHC-I pathway components in Bl6 mice, whereas no alterations were observed in 129Sv. We observed significant positive correlations between bodyweight decline and expressions of MHC-I components in the olfactory bulbs of Bl6 mice and the frontal cortex of 129Sv, highlighting different brain regions most affected by LPS in these strains. Our findings suggest that the brains of Bl6 mice exist in a more immunocompetent state compared to 129Sv mice.Cell-based therapies hold great promise in re-establishing organ function for many diseases, including untreatable lung diseases such as idiopathic pulmonary fibrosis (IPF). However, many hurdles still remain, in part due to our lack of knowledge about the disease-driving mechanisms that may affect the cellular niche and thereby possibly hinder the function of any transplanted cells by imposing the disease phenotype onto the newly generated progeny. Recent findings have demonstrated increased ciliation of lung cells from IPF patients, but how this affects ciliated cell function and the airway milieu is not well-known. Here, we performed single-cell RNA sequencing on primary ciliated (FOXJ1+) cells isolated from IPF patients and from healthy control donors. The sequencing identified multiple biological processes, such as cilium morphogenesis and cell signaling, that were significantly changed between IPF and healthy ciliated cells. Ferritin light chain (FTL) was downregulated in IPF, which suggests that iron metabolism may be affected in the IPF ciliated cells. The RNA expression was confirmed at the protein level with histological localization in lung tissue, prompting future functional assays to reveal the potential role of FTL. Taken together, our data demonstrate the importance of careful analyses in pure cell populations to better understand the IPF disease mechanism.Early identification and management of precancerous lesions at high risk of developing cancers is the most effective and economical way to reduce the incidence, mortality, and morbidity of cancers as well as minimizing treatment-related complications, including pain, impaired functions, and disfiguration. Reliable cancer-risk-predictive markers play an important role in enabling evidence-based decision making as well as providing mechanistic insight into the malignant conversion of precancerous lesions. The focus of this article is to review updates on markers that may predict the risk of oral premalignant lesions (OPLs) in developing into oral squamous cell carcinomas (OSCCs), which can logically be discovered only by prospective or retrospective longitudinal studies that analyze pre-progression OPL samples with long-term follow-up outcomes. These risk-predictive markers are different from those that prognosticate the survival outcome of cancers after they have been diagnosed and treated, or those that differentiate between different lesion types and stages. Up-to-date knowledge on cancer-risk-predictive markers discovered by longitudinally followed studies will be reviewed. The goal of this endeavor is to use this information as a starting point to address some key challenges limiting our progress in this area in the hope of achieving effective translation of research discoveries into new clinical interventions.Although neuropsychiatric symptoms (NPS) are common and severely affect older people with cognitive decline, little is known about their underlying molecular mechanisms and relationships with Alzheimer’s disease (AD). The aim of this study was to identify and characterize cerebrospinal fluid (CSF) proteome alterations related to NPS. In a longitudinally followed-up cohort of subjects with normal cognition and patients with cognitive impairment (MCI and mild dementia) from a memory clinic setting, we quantified a panel of 790 proteins in CSF using an untargeted shotgun proteomic workflow. Regression models and pathway enrichment analysis were used to investigate protein alterations related to NPS, and to explore relationships with AD pathology and cognitive decline at follow-up visits. Regression analysis selected 27 CSF proteins associated with NPS. These associations were independent of the presence of cerebral AD pathology (defined as CSF p-tau181/Aβ1-42 > 0.0779, center cutoff). Gene ontology enrichment showed abundance alterations of proteins related to cell adhesion, immune response, and lipid metabolism, among others, in relation to NPS. Out of the selected proteins, three were associated with accelerated cognitive decline at follow-up visits after controlling for possible confounders. Specific CSF proteome alterations underlying NPS may both represent pathophysiological processes independent from AD and accelerate clinical disease progression.The aim of this study was to validate the use of human brain organoids (hBOs) to investigate the therapeutic potential and mechanism of human-neural-crest-derived nasal turbinate stem cells (hNTSCs) in models of Alzheimer’s disease (AD). We generated hBOs from human induced pluripotent stem cells, investigated their characteristics according to neuronal markers and electrophysiological features, and then evaluated the protective effect of hNTSCs against amyloid-β peptide (Aβ1-42) neurotoxic activity in vitro in hBOs and in vivo in a mouse model of AD. Treatment of hBOs with Aβ1-42 induced neuronal cell death concomitant with decreased expression of neuronal markers, which was suppressed by hNTSCs cocultured under Aβ1-42 exposure. Cytokine array showed a significantly decreased level of osteopontin (OPN) in hBOs with hNTSC coculture compared with hBOs only in the presence of Aβ1-42. Silencing OPN via siRNA suppressed Aβ-induced neuronal cell death in cell culture. Notably, compared with PBS, hNTSC transplantation significantly enhanced performance on the Morris water maze, with reduced levels of OPN after transplantation in a mouse model of AD. These findings reveal that hBO models are useful to evaluate the therapeutic effect and mechanism of stem cells for application in treating AD.Mechanical ventilation (MV) is a clinical tool that provides respiratory support to patients unable to maintain adequate alveolar ventilation on their own. Although MV is often a life-saving intervention in critically ill patients, an undesired side-effect of prolonged MV is the rapid occurrence of diaphragmatic atrophy due to accelerated proteolysis and depressed protein synthesis. Investigations into the mechanism(s) responsible for MV-induced diaphragmatic atrophy reveal that activation of the calcium-activated protease, calpain, plays a key role in accelerating proteolysis in diaphragm muscle fibers. Moreover, active calpain has been reported to block signaling events that promote protein synthesis (i.e., inhibition of mammalian target of rapamycin (mTOR) activation). While this finding suggests that active calpain can depress muscle protein synthesis, this postulate has not been experimentally verified. Therefore, we tested the hypothesis that active calpain plays a key role in the MV-induced depression induced depression of protein synthesis within diaphragm fibers.Tracheal grafts introduce the possibility to treat airway pathologies that require resection. While there has been success with engraftment of the surface airway epithelium (SAE) onto decellularized tracheas, there has been minimal advancement in regenerating the submucosal glands (SMGs). We designed a cost-effective open-system perfusion bioreactor to investigate the engraftment potential of ferret SAEs and murine myoepithelial cells (MECs) on a partly decellularized ferret trachea with the goal of creating a fully functional tracheal replacement. An air-liquid interface was also arranged by perfusing humidified air through the lumen of a recellularized conduit to induce differentiation. Our versatile bioreactor design was shown to support the successful partial decellularization and recellularization of ferret tracheas. The decellularized grafts maintained biomechanical integrity and chondrocyte viability, consistent with other publications. The scaffolds supported SAE basal cell engraftment, and early differentiation was observed once an air-liquid interface had been established.