Die Hemmung der sauren Sphingomyelinase schützt Mäuse vor Lungenödem bei systemischen Staphylococcus aureus Infektionen

Lungenödem, welches mit einer erhöhten Gefäßpermeabilität einher- geht, ist eine ernsthafte Komplikation von Staphylococcus aureus-induzierter Sepsis und damit eine wichtige klinische Komplikation, die auch häufig letal endet. Wir untersuchten die Rolle des sauren Sphingomyelinase (ASM) / Ceramid Systems bei der Entwicklung eines S. aureus induzierten Lungenödems. Unsere Ergebnisse zeigen, dass ein genetischer Mangel oder eine pharmakologische Hemmung der Asm bei Mäusen, die mit S. aureus infiziert sind, Lungenödem verhindert. Das ASM / Ceramid System löste die Bildung reaktiver Sauerstoffspezies (ROS) aus, die wiederum den Abbau von Tight Junction-Proteinen und damit ein Lungenödem induzierten. Eine Behandlung infizierter Mäuse mit Amitriptylin, einem potenten Inhibitor der ASM, schützte die Mäuse vor S. aureus induziertem Lungenödem, hatte aber keine bakteriostatische oder bakterizide Wirkung. Die Behandlung mit Antibiotika verringerte dagegen zwar die Bakterienzahlen, schützte die Mäuse aber nicht vor Lungenödem. Erst die Kombination von Antibiotika und Amitriptylin reduzierte sowohl Lungenödem als auch Bakteriämie und schützte Mäuse vor letaler Sepsis und Lungendysfunktion. Die Kombination der beiden Medikamente könnte eine neuartige Behandlungsoption einer Sepsis darstellen.Pulmonary edema associated with increased vascular permeability is a severe complication of Staphylococcus aureus–induced sepsis and an important cause of human pathology and death. We investigated the role of the acid sphingomyelinase (Asm)/ceramide system in the development of lung edema caused by S. aureus. Our findings demonstrate that genetic deficiency or pharmacologic inhibition of Asm prevented lung edema in mice infected with S. aureus. The Asm/ceramide system triggered the formation of reactive oxygen species (ROS), resulting in degradation of tight junction proteins followed by lung edema. Treatment of infected mice with amitriptyline, a potent inhibitor of Asm, protected mice from lung edema caused by S. aureus, but had no effect on bacterial numbers. In turn, treatment with antibiotics reduced bacterial numbers but did not protect mice from lung edema. In contrast, the combination of antibiotics and amitriptyline reduced both pulmonary edema and bacteremia protecting mice from lethal sepsis and lung dysfunction suggesting the combination of both drugs as novel treatment option for sepsis

Tetraspanins: Novel Molecular Regulators of Gastric Cancer

Gastric cancer is the fourth and fifth most common cancer worldwide in men and women, respectively. However, patients with an advanced stage of gastric cancer still have a poor prognosis and low overall survival rate. The tetraspanins belong to a protein superfamily with four hydrophobic transmembrane domains and 33 mammalian tetraspanins are ubiquitously distributed in various cells and tissues. They interact with other membrane proteins to form tetraspanin-enriched microdomains and serve a variety of functions including cell adhesion, invasion, motility, cell fusion, virus infection, and signal transduction. In this review, we summarize multiple utilities of tetraspanins in the progression of gastric cancer and the underlying molecular mechanisms. In general, the expression of TSPAN8, CD151, TSPAN1, and TSPAN4 is increased in gastric cancer tissues and enhance the proliferation and invasion of gastric cancer cells, while CD81, CD82, TSPAN5, TSPAN9, and TSPAN21 are downregulated and suppress gastric cancer cell growth. In terms of cell motility regulation, CD9, CD63 and CD82 are metastasis suppressors and the expression level is inversely associated with lymph node metastasis. We also review the clinicopathological significance of tetraspanins in gastric cancer including therapeutic targets, the development of drug resistance and prognosis prediction. Finally, we discuss the potential clinical value and current limitations of tetraspanins in gastric cancer treatments, and provide some guidance for future research

Changes in respiratory structure and function after traumatic cervical spinal cord injury: observations from spinal cord and brain

Respiratory difficulties and mortality following severe cervical spinal cord injury (CSCI) result primarily from malfunctions of respiratory pathways and the paralyzed diaphragm. Nonetheless, individuals with CSCI can experience partial recovery of respiratory function through respiratory neuroplasticity. For decades, researchers have revealed the potential mechanism of respiratory nerve plasticity after CSCI, and have made progress in tissue healing and functional recovery. While most existing studies on respiratory plasticity after spinal cord injuries have focused on the cervical spinal cord, there is a paucity of research on respiratory-related brain structures following such injuries. Given the interconnectedness of the spinal cord and the brain, traumatic changes to the former can also impact the latter. Consequently, are there other potential therapeutic targets to consider? This review introduces the anatomy and physiology of typical respiratory centers, explores alterations in respiratory function following spinal cord injuries, and delves into the structural foundations of modified respiratory function in patients with CSCI. Additionally, we propose that magnetic resonance neuroimaging holds promise in the study of respiratory function post-CSCI. By studying respiratory plasticity in the brain and spinal cord after CSCI, we hope to guide future clinical work

Crop pest image classification based on improved densely connected convolutional network

IntroductionCrop pests have a great impact on the quality and yield of crops. The use of deep learning for the identification of crop pests is important for crop precise management.MethodsTo address the lack of data set and poor classification accuracy in current pest research, a large-scale pest data set named HQIP102 is built and the pest identification model named MADN is proposed. There are some problems with the IP102 large crop pest dataset, such as some pest categories are wrong and pest subjects are missing from the images. In this study, the IP102 data set was carefully filtered to obtain the HQIP102 data set, which contains 47,393 images of 102 pest classes on eight crops. The MADN model improves the representation capability of DenseNet in three aspects. Firstly, the Selective Kernel unit is introduced into the DenseNet model, which can adaptively adjust the size of the receptive field according to the input and capture target objects of different sizes more effectively. Secondly, in order to make the features obey a stable distribution, the Representative Batch Normalization module is used in the DenseNet model. In addition, adaptive selection of whether to activate neurons can improve the performance of the network, for which the ACON activation function is used in the DenseNet model. Finally, the MADN model is constituted by ensemble learning.ResultsExperimental results show that MADN achieved an accuracy and F1Score of 75.28% and 65.46% on the HQIP102 data set, an improvement of 5.17 percentage points and 5.20 percentage points compared to the pre-improvement DenseNet-121. Compared with ResNet-101, the accuracy and F1Score of MADN model improved by 10.48 percentage points and 10.56 percentage points, while the parameters size decreased by 35.37%. Deploying models to cloud servers with mobile application provides help in securing crop yield and quality

Optimization of Ganoderma leucocontextum Fermented Tea Medium Formula Based on High-yield Extracellular Crude

To investigate the optimal nutritional conditions and their contributing factors for the secretion of extracellular crude polysaccharides with Ganoderma leucocontextum on a liquid tea substrate, this study optimized the nutritional conditions of its extracellular crude polysaccharides formation by orthogonal experiment and analysis of variance on the basis of the single-factor test, and explored the relevance between its liquid culture characteristics and the secretion of extracellular crude polysaccharides using correlation and path analyses. The results of study revealed that the greatest output of extracellular crude polysaccharide (1.49±0.33 g/L) was achieved on a tea culture medium of 50 g/L potato, 40 g/L glucose, 3 g/L laterite, 20 g/L Pu'er tea and 0.075 mm tea powder particle size, and was affected by each nutritional condition in the descending order of glucose>tea variety>laterite>potato>tea powder particle size. Moreover, the secretion of extracellular crude polysaccharides in G. leucocontextum was significantly impacted by the soluble solids of the fermentation broth and the number of mycelium balls, with the former having the greatest indirect effect while the latter, the greatest direct and combined effect on it. In conclusion, the nutritional conditions (variety, concentration, particle size, etc.) of the tea culture medium and the liquid culture characteristics of G. leucocontextum exerted a significant and interactive effect on the secretion of extracellular crude polysaccharides, and the aforesaid results may provide a theoretical reference for extraction of polysaccharides from this mushroom and development of it as functional foods

Identification of crucial modules and genes associated with backfat tissue development by WGCNA in Ningxiang pigs

Fat deposition is an economically important trait in pigs. Ningxiang pig, one of the four famous indigenous breeds in China, is characterized by high fat content. The underlying gene expression pattern in different developmental periods of backfat tissue remains unclear, and the purpose of this investigation is to explore the potential molecular regulators of backfat tissue development in Ningxiang pigs. Backfat tissue (three samples for each stage) was initially collected from different developmental stages (60, 120, 180, 240, 300, and 360 days after birth), and histological analysis and RNA sequencing (RNA-seq) were then conducted. Fragments per kilobase of transcript per million (FPKM) method was used to qualify gene expressions, and differentially expressed genes (DEGs) were identified. Furthermore, strongly co-expressed genes in modules, which were named by color, were clustered by Weighted gene co-expression network analysis (WGCNA) based on dynamic tree cutting algorithm. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) enrichment were subsequently implemented, and hub genes were described in each module. Finally, QPCR analysis was employed to validate RNA-seq data. The results showed that adipocyte area increased and adipocyte number decreased with development of backfat tissue. A total of 1,024 DEGs were identified in five comparison groups (120 days vs. 60 days, 180 days vs. 120 days, 240 days vs. 180 days, 300 days vs. 240 days, and 360 days vs. 300 days). The turquoise, red, pink, paleturquoise, darkorange, and darkgreen module had the highest correlation coefficient with 60, 120, 180, 240, 300, and 360 days developmental stage, while the tan, black and turquoise module had strong relationship with backfat thickness, adipocyte area, and adipocyte number, respectively. Thirteen hub genes (ACSL1, ACOX1, FN1, DCN, CHST13, COL1A1, COL1A2, COL6A3, COL5A1, COL14A1, OAZ3, DNM1, and SELP) were recognized. ACSL1 and ACOX1 might perform function in the early developmental stage of backfat tissue (60 days), and FN1, DCN, COL1A1, COL1A2, COL5A1, COL6A3, and COL14A1 have unignorable position in backfat tissue around 120 days developmental stage. Besides, hub genes SELP and DNM1 in modules significantly associated with backfat thickness and adipocyte area might be involved in the process of backfat tissue development. These findings contribute to understand the integrated mechanism underlying backfat tissue development and promote the progress of genetic improvement in Ningxiang pigs

Determination of reference intervals of serum levels of human epididymis protein 4 (HE4) in Chinese women

The detailed numbers of subjects from different centers. (DOCX 17.3 kb

Frequent alterations in cytoskeleton remodelling genes in primary and metastatic lung adenocarcinomas

The landscape of genetic alterations in lung adenocarcinoma derived from Asian patients is largely uncharacterized. Here we present an integrated genomic and transcriptomic analysis of 335 primary lung adenocarcinomas and 35 corresponding lymph node metastases from Chinese patients. Altogether 13 significantly mutated genes are identified, including the most commonly mutated gene TP53 and novel mutation targets such as RHPN2, GLI3 and MRC2. TP53 mutations are furthermore significantly enriched in tumours from patients harbouring metastases. Genes regulating cytoskeleton remodelling processes are also frequently altered, especially in metastatic samples, of which the high expression level of IQGAP3 is identified as a marker for poor prognosis. Our study represents the first large-scale sequencing effort on lung adenocarcinoma in Asian patients and provides a comprehensive mutational landscape for both primary and metastatic tumours. This may thus form a basis for personalized medical care and shed light on the molecular pathogenesis of metastatic lung adenocarcinoma