Case report: Catastrophic event: neonatal gastric perforation and complication of capillary leak syndrome

Neonatal gastric perforation (NGP) is a rare, but life-threatening condition that can lead to serious conditions, such as capillary leak syndrome (CLS). Here, we present the case of a preterm male infant with NGP complicated by CLS after stomach repair. The patient was born at 33 2/7 weeks, weighed 1,770 g, and was diagnosed with respiratory distress syndrome. On the fourth day of life, the patient presented with distention and an unstable cardiovascular system. Routine blood tests revealed a white blood cell count of 2.4 × 109/L. Chest and abdominal radiography revealed a pneumoperitoneum, suggesting a gastrointestinal perforation. The patient was urgently transferred to a tertiary hospital for exploratory laparotomy, where a 2 cm diameter perforation was discovered in the stomach wall and subsequently repaired. Pathological findings indicated the absence of a muscular layer in the stomach wall. The patient unexpectedly developed CLS postoperatively, leading to multiorgan dysfunction and eventual death. The underlying pathological mechanism of NGP-induced CLS may be related to severe chemical peritonitis, sepsis, endothelial glycocalyx dysfunction, enhanced systemic inflammation, and translocation of the gut microbiota, causing endothelial hyperpermeability. Notablely, abdominal surgery itself can be a significant triggering factor for CLS occurrence. Complications of NGP and CLS are extremely dangerous. Investigating the mechanism by which NGP triggers CLS could potentially improve the prognosis. Conservative treatment for pneumoperitoneum secondary to gastric perforation may be a reasonable option, especially when the condition of the patient is unstable

Neuromatch Academy: a 3-week, online summer school in computational neuroscience

Neuromatch Academy (https://academy.neuromatch.io; (van Viegen et al., 2021)) was designed as an online summer school to cover the basics of computational neuroscience in three weeks. The materials cover dominant and emerging computational neuroscience tools, how they complement one another, and specifically focus on how they can help us to better understand how the brain functions. An original component of the materials is its focus on modeling choices, i.e. how do we choose the right approach, how do we build models, and how can we evaluate models to determine if they provide real (meaningful) insight. This meta-modeling component of the instructional materials asks what questions can be answered by different techniques, and how to apply them meaningfully to get insight about brain function

Screening out irrelevant cell-based models of disease

The common and persistent failures to translate promising preclinical drug candidates into clinical success highlight the limited effectiveness of disease models currently used in drug discovery. An apparent reluctance to explore and adopt alternative cell-and tissue-based model systems, coupled with a detachment from clinical practice during assay validation, contributes to ineffective translational research. To help address these issues and stimulate debate, here we propose a set of principles to facilitate the definition and development of disease-relevant assays, and we discuss new opportunities for exploiting the latest advances in cell-based assay technologies in drug discovery, including induced pluripotent stem cells, three-dimensional (3D) co-culture and organ-on-a-chip systems, complemented by advances in single-cell imaging and gene editing technologies. Funding to support precompetitive, multidisciplinary collaborations to develop novel preclinical models and cell-based screening technologies could have a key role in improving their clinical relevance, and ultimately increase clinical success rates

Propyl Gallate Treatment Improves the Postharvest Quality of Winter Jujube (<i>Zizyphus jujuba</i> Mill. cv. Dongzao) by Regulating Antioxidant Metabolism and Maintaining the Structure of Peel

The quality and color of winter jujube fruits are easy to change after harvest. We studied the regulation mechanism of propyl gallate (PG) on post-harvest physiological quality of winter jujube, from the perspective of antioxidant metabolism and peel structure. In our research, winter jujube fruits were treated with 0.001 mol L−1 PG solution for 20 min. Our results showed that PG delayed the development of peel color, and improved the firmness, total soluble solids (TSS), and titratable acid (TA) of winter jujube. Meanwhile, the PG treatment had higher content of total phenols, total flavonoids, ascorbic acid (AsA), and reduced glutathione (GSH), and kept the enzyme activity including superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), and peroxidase (POD) at a higher level. PG treatment reduced membrane oxidative damage and maintained the integrity of pericarp structure by reducing electrolyte leakage (EL), lipoxygenase activity (LOX), hydrogen peroxide (H2O2), and malondialdehyde (MDA) content in the peel. Accordingly, PG improved the postharvest quality of jujube fruits by regulating antioxidant metabolism and maintaining the structure of peel. The appropriate concentration of PG has good application potential in the storage and preservation of fresh fruits such as winter jujube

Strain-Specific Effects of <i>Bifidobacterium longum</i> on Hypercholesterolemic Rats and Potential Mechanisms

Hypercholesterolemia is an independent risk factor of cardiovascular disease, which is among the major causes of death worldwide. The aim of this study was to explore whether Bifidobacterium longum strains exerted intra-species differences in cholesterol-lowering effects in hypercholesterolemic rats and to investigate the potential mechanisms. SD rats underwent gavage with each B. longum strain (CCFM 1077, I3, J3 and B3) daily for 28 days. B. longum CCFM 1077 exerted the most potent cholesterol-lowering effect, followed by B. longum I3 and B3, whereas B. longum B3 had no effect in alleviating hypercholesterolemia. Divergent alleviation of different B. longum strains on hypercholesterolemia can be attributed to the differences in bile salt deconjugation ability and cholesterol assimilation ability in vitro. By 16S rRNA metagenomics analysis, the relative abundance of beneficial genus increased in the B. longum CCFM 1077 treatment group. The expression of key genes involved in cholesterol metabolism were also altered after the B. longum CCFM 1077 treatment. In conclusion, B. longum exhibits strain-specific effects in the alleviation of hypercholesterolemia, mainly due to differences in bacterial characteristics, bile salt deconjugation ability, cholesterol assimilation ability, expressions of key genes involved in cholesterol metabolism and alterations of gut microbiota

Selection and mechanism exploration for salt-tolerant genes in tomato

<p>High salinity is a major destructive environmental factor limiting the growth and productivity of plants. In this study, we selected 8 significantly enriched salt stress-related pathways and 17 differentially expressed genes based on RNA sequencing (RNA-Seq). We verified the salt tolerance of the selected key genes using qRT-PCR and combined molecular biology and physiology to explore the salt tolerance mechanism of <i>ASR2-like</i> and <i>ASR3-like</i> genes using the salt-tolerant tomato cultivar LA2711 and the salt-sensitive tomato cultivar ZS-5. The results showed that exogenous ABA significantly increased all physiological indexes but decreased the transcript levels of two target genes compared with untreated controls under salt stress, suggesting that the two genes play an important role in salt tolerance in the form of negative dependence on ABA. Combined with the ABA adaptation pattern and the relationship between the target gene and ABA in the process of response to salt stress, we concluded that <i>ASR2-like</i> and <i>ASR3-like</i> might respond to salt stress by increasing the activities of ROS-scavenging enzymes and proline content via negative dependence on ABA. Taken together, these results provide a good resource for the genetic improvement of tomato and a theoretical basis for obtaining tomato varieties with high resistance to salt.</p

Dihydromyricetin Attenuates TNF-α-Induced Endothelial Dysfunction through miR-21-Mediated DDAH1/ADMA/NO Signal Pathway

Accumulating studies demonstrate that dihydromyricetin (DMY), a compound extracted from Chinese traditional herb, Ampelopsis grossedentata, attenuates atherosclerotic process by improvement of endothelial dysfunction. However, the underlying mechanism remains poorly understood. Thus, the aim of this study is to investigate the potential mechanism behind the attenuating effects of DMY on tumor necrosis factor alpha- (TNF-α-) induced endothelial dysfunction. In response to TNF-α, microRNA-21 (miR-21) expression was significantly increased in human umbilical vein endothelial cells (HUVECs), in line with impaired endothelial dysfunction as evidenced by decreased tube formation and migration, endothelial nitric oxide synthase (eNOS) (ser1177) phosphorylation, dimethylarginine dimethylaminohydrolases 1 (DDAH1) expression and metabolic activity, and nitric oxide (NO) concentration as well as increased asymmetric dimethylarginine (ADMA) levels. In contrast, DMY or blockade of miR-21 expression ameliorated endothelial dysfunction in HUVECs treated with TNF-α through downregulation of miR-21 expression, whereas these effects were abolished by overexpression of miR-21. In addition, using a nonspecific NOS inhibitor, L-NAME, also abrogated the attenuating effects of DMY on endothelial dysfunction. Taken together, these data demonstrated that miR-21-mediated DDAH1/ADMA/NO signal pathway plays an important role in TNF-α-induced endothelial dysfunction, and DMY attenuated endothelial dysfunction induced by TNF-α in a miR-21-dependent manner