Caspase-3/GSDME dependent pyroptosis contributes to offspring lung injury induced by gestational PFOS exposure via PERK/ATF4 signaling.

Perfluorooctane sulfonate (PFOS) is widely used in industry and consumer products. Previous studies have showed that PFOS gestational exposure is associated with offspring lung damage in rat. However, the underlying mechanisms remain poorly understood. In this study, we investigated the role of gasdermin E (GSDME) in lung injury of offspring and its underlying mechanisms using in vivo and in vitro approaches. Pregnant SD rats were exposed to PFOS (1 mg/kg BW/d) between gestational day 12-18, and the lung tissue of the offspring was evaluated on postnatal day 7. PFOS treated animals exhibited alveolar septal thickening and inflammation-related damages, with an increased expression of GSDME in alveolar type II epithelial cells (AECII). Furthermore, in vitro experiments demonstrated that PFOS exposure (with 225 µM and up) upregulated the caspase-3/GSDME signaling pathway in AECII. Also, ultrastructure analysis revealed significant changes in the endoplasmic reticulum (ER) structure in PFOS-induced pyroptotic cells, which is consistent with the ER stress detected in these cells. Additionally, PFOS exposure led to increased expression of ER stress-related proteins, including p-PERK, p-eIF2α, ATF4, and CHOP. Subsequently, using specific inhibitors, we found that the PERK/ATF4 pathway acted as an upstream signal regulating GSDME-dependent pyroptosis. Overall, our findings show that GSDME-dependent pyroptosis plays a crucial role in the lung injury induced by gestational PFOS exposure, and the PERK/ATF4 pathway may function as a possible mediator of this process.

Effective treatment of a child with adenoidal hypertrophy and severe asthma by omalizumab: a case report.

BACKGROUND: Childhood adenoid hypertrophy (AH) is common and is often associated with allergic asthma, resulting in complications like obstructive sleep apnea syndrome (OSAS). Management of the disease and its complications is often challenging. CASE PRESENTATION: We report here a case of a 10-year-old boy who suffered from severe allergic asthma and rhinitis and was treated with omalizumab. Before the treatment, the childhood asthma control test (C-ACT, 14), visal analog scale (VAS, 7) and lung function (mild obstructive ventilation dysfunction and moderate to severe dysfunction in ventilation in small airway) were seriously affected. Polysomnography showed OSAS (apnea hypopnea index, AHI, 6.4), low hypooxia saturation (lowest pulse oxygen saturation, LoSpO2, 70%), and adenoid hypertrophy (at grade III). After treating with omalizumab for 4 weeks (once treatment), the ventilation function, symptoms of asthma and allergic rhinitis (C-ACT, 24; VAS, 2), and OSAS (AHI: 1.8 and LoSpO2: 92.6%) were all improved, and the adenoids size was also significantly reduced to grade II. And during the following 3 times of treatment, the allergic symptoms continued improving, and the size of adenoid was reduced to grade I. Even 6.5 months after cessation of omalizumab, the size of adenoid remained at grade I. CONCLUSION: This is the first documented case that childhood adenoid hypertrophy can be significantly improved by omalizumab.

An Infant With Interstitial Lung Disease of Rare Cause.

CASE PRESENTATION: An 11-month-old boy was admitted to our hospital because of "recurrent cough with intermittent dyspnea for more than 8 months, aggravated for 1 month." The baby began experiencing a recurrent milk-choking problem within 1.5 months after birth. He had been hospitalized four times, but the symptoms recurred. One month previously, the symptoms were aggravated and a chest CT scan performed at outside hospital showed interstitial changes. Pediatric bronchoscopy revealed bronchial inflammatory features, with hemosiderin-laden macrophages being found in BAL fluid (BALF). Also, periodic acid-Schiff (PAS) staining showed positive results, which indicated the possibility of pulmonary alveolar proteinosis (PAP) or idiopathic pulmonary hemosiderosis (IPH).

Intelligent grading method for walnut kernels based on deep learning and physiological indicators.

Walnut grading is an important step before the product enters the market. However, traditional walnut grading primarily relies on manual assessment of physiological features, which is difficult to implement efficiently. Furthermore, walnut kernel grading is, at present, relatively unsophisticated. Therefore, this study proposes a novel deep-learning model based on a spatial attention mechanism and SE-network structure to grade walnut kernels using machine vision to ensure accuracy and improve assessment efficiency. In this experiment, we found through the literature that both the lightness (L* value) and malondialdehyde (MDA) contens of walnut kernels were correlated with the oxidation phenomenon in walnuts. Subsequently, we clustered four partitionings using the L* values. We then used the MDA values to verify the rationality of these partitionings. Finally, four network models were used for comparison and training: VGG19, EfficientNetB7, ResNet152V2, and spatial attention and spatial enhancement network combined with ResNet152V2 (ResNet152V2-SA-SE). We found that the ResNet152V2-SA-SE model exhibited the best performance, with a maximum test set accuracy of 92.2%. The test set accuracy was improved by 6.2, 63.2, and 74.1% compared with that of ResNet152V2, EfficientNetB7, and VGG19, respectively. Our testing demonstrated that combining spatial attention and spatial enhancement methods improved the recognition of target locations and intrinsic information, while decreasing the attention given to non-target regions. Experiments have demonstrated that combining spatial attention mechanisms with SE networks increases focus on recognizing target locations and intrinsic information, while decreasing focus on non-target regions. Finally, by comparing different learning rates, regularization methods, and batch sizes of the model, we found that the training performance of the model was optimal with a learning rate of 0.001, a batch size of 128, and no regularization methods. In conclusion, this study demonstrated that the ResNet152V2-SA-SE network model was effective in the detection and evaluation of the walnut kernels.

Increasing urinary podocyte mRNA excretion and progressive podocyte loss in kidney contribute to the high risk of long-term renal disease caused by preterm birth.

Podocyte abnormalities are common mechanism driving the progression of glomerular diseases, which account for most chronic kidney diseases (CKDs). However, the role of podocyte in the mechanism of high-risk long-term CKD caused by prematurity has not been well clarified. In present study, urine samples of 86 preterm infants and 32 full-term infants were collected, and podocyte-specific podocin mRNA levels in urine pellet were applied to indicate urinary podocyte mRNA excretion. In addition, in a preterm animal rat model, preterm rats were identified by delivery 2 days early. From the age of 3 weeks-12 months, urine samples were collected to examine podocyte mRNA excretion by measuring podocyte-specific podocin mRNA levels. Kidney samples at the age of 3 weeks, 2 months, and 12 months were collected from 8, 5 and 6 preterm rats and 9, 6 and 8 full-term rats, respectively, to examine podocyte density and podocyte area by measuring the podocyte specific nuclear marker WT-1 and the podocyte specific marker synaptopodin. As results, a more than threefold increase of urinary podocyte-specific podocin mRNA excretion rate was found in preterm infants compared with full-term infants. In addition, there was negative correlation between gestational age at birth and urinary podocin mRNA excretion. In preterm rats, a reduction in the total number of differentiated podocytes in glomeruli and an increased podocyte podocin mRNA excretion rate in urine were detected at the end of kidney differentiation. Moreover, long-term follow-up data in preterm rats showed there was an increased the risk of renal disease indicated by persistent podocyte mRNA loss, proteinuria, and enlarged glomeruli. In conclusion, increasing podocyte mRNA excretion in urine and podocyte loss in kidney led by prematurity drive the progression of long-term abnormal kidney function and could potentially explain the high risk of long-term CKD in preterm infants.

Determination of the dynamic cellular transcriptional profiles during kidney development from birth to maturity in rats by single-cell RNA sequencing.

Recent single-cell RNA sequencing (scRNA-seq) analyses have offered much insight into the gene expression profiles in early-stage kidney development. However, comprehensive gene expression profiles from mid- and late-stage kidney development are lacking. In the present study, by using the scRNA-seq technique, we analyzed 54,704 rat kidney cells from just after birth to adulthood (six time points: postnatal days 0, 2, 5, 10, 20, and 56) including the mid and late stages of kidney development. Twenty-five original clusters and 13 different cell types were identified during these stages. Gene expression in these 13 cell types was mapped, and single cell atlas of the rat kidney from birth to maturity ( http://youngbearlab.com ) was built to enable users to search for a gene of interest and to evaluate its expression in different cells. The variation trend of six major types of kidney cells-intercalated cells of the collecting duct (CD-ICs), principal cells of the collecting duct (CD-PCs), cells of the distal convoluted tubules (DCTs), cells of the loop of Henle (LOH), podocytes (PDs), and cells of the proximal tubules (PTs)-during six postnatal time points was demonstrated. The trajectory of rat kidney development and the order of induction of the six major types of kidney cells from just after birth to maturity were determined. In addition, features of the dynamically changing genes as well as transcription factors during postnatal rat kidney development were identified. The present study provides a resource for achieving a deep understanding of the molecular basis of and regulatory events in the mid and late stages of kidney development.

Structural and quantitative alterations of gut microbiota in experimental small bowel obstruction.

OBJECTIVE: To investigate structural and quantitative alterations of gut microbiota in an experimental model of small bowel obstruction. METHOD: A rat model of small bowel obstruction was established by using a polyvinyl chloride ring surgically placed surrounding the terminal ileum. The alterations of gut microbiota were studied after intestinal obstruction. Intraluminal fecal samples proximal to the obstruction were collected at different time points (24, 48 and 72 hours after obstruction) and analyzed by 16s rDNA high-throughput sequencing technology and quantitative PCR (qPCR) for target bacterial groups. Furthermore, intestinal claudin-1 mRNA expression was examined by real-time polymerase chain reaction analysis, and serum sIgA, IFABP and TFF3 levels were determined by enzyme-linked immunosorbent assay. RESULTS: Small bowel obstruction led to significant bacterial overgrowth and profound alterations in gut microbiota composition and diversity. At the phylum level, the 16S rDNA sequences showed a marked decrease in the relative abundance of Firmicutes and increased abundance of Proteobacteria, Verrucomicrobia and Bacteroidetes. The qPCR analysis showed the absolute quantity of total bacteria increased significantly within 24 hours but did not change distinctly from 24 to 72 hours. Further indicators of intestinal mucosa damage and were observed as claudin-1 gene expression, sIgA and TFF3 levels decreased and IFABP level increased with prolonged obstruction. CONCLUSION: Small bowel obstruction can cause significant structural and quantitative alterations of gut microbiota and induce disruption of gut mucosa barrier.