Background:Evidence from both clinical and experimental research indicates that the immune-brain interaction plays a pivotal role in the pathophysiology of depression. A multi-protein complex of the innate immune system, the NLRP3 inflammasome regulates cleavage and secretion of proinflammatory cytokine interleukin-1β. The inflammasome detects various pathogen-associated molecule patterns and damage-associated molecule patterns, which then leads to a series of immune-inflammatory reactions.Methods:To explore the role of inflammasome activation in the underlying biological mechanisms of depression, we established a mouse model of depression with unpredictable chronic mild stress.Results:Mice subjected to chronic mild stress for 4 weeks had significantly higher serum corticosterone levels, serum interleukin-1β levels, and hippocampal active interleukin-1β protein levels. They also displayed depressive-like symptoms, including decreased sucrose preference and increased immobility time. Moreover, the hippocampi of chronic mild stress-exposed mice had significantly higher activity of caspase-1, which accompanied by higher protein levels of NLRP3 and the apoptotic speck-containing protein with a card. Pretreatment with the NLRP3 inflammasome inhibitor VX-765 decreased serum and hippocampal levels of interleukin-1β protein and significantly moderated the depressive-like behaviors induced by chronic mild stress.Conclusions:These data suggest the NLRP3 inflammasome mediates stress-induced depression via immune activation. Future procedures targeting the NLRP3 inflammasome may have promising effects in the prevention and treatment of depression.

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Peripheral neuropathy is a chronic complication of diabetes mellitus. To investigated the efficacy and safety of the extended treatment of diabetic peripheral neuropathy with thymosin β4 (Tβ4), male diabetic mice (db/db) at the age of 24 weeks were treated with Tβ4 or saline for 16 consecutive weeks. Treatment of diabetic mice with Tβ4 significantly improved motor (MCV) and sensory (SCV) conduction velocity in the sciatic nerve and the thermal and mechanical latency. However, Tβ4 treatment did not significantly alter blood glucose levels. Treatment with Tβ4 significantly increased intraepidermal nerve fiber density. Furthermore, Tβ4 counteracted the diabetes-induced axon diameter and myelin thickness reductions and the g-ratio increase in sciatic nerve. In vitro, compared with dorsal root ganglia (DRG) neurons derived from nondiabetic mice, DRG neurons derived from diabetic mice exhibited significantly decreased neurite outgrowth, whereas Tβ4 promoted neurite growth in these diabetic DRG neurons. Blockage of the Ang1/Tie2 signaling pathway with a neutralized antibody against Tie2 abolished Tβ4-increased neurite outgrowth. Our data demonstrate that extended Tβ4 treatment ameliorates diabetic-induced axonal degeneration and demyelination, which likely contribute to therapeutic effect of Tβ4 on diabetic neuropathy. The Ang1/Tie2 pathway may mediate Tβ4-induced axonal remodeling.

Background: Culture-negative late-onset sepsis (LOS) is commonly diagnosed in neonatal intensive care units, while the outcomes of neonatal culture-negative LOS are not reported for large cohorts. This study aimed to examine the incidence and neonatal outcomes for culture-negative LOS in a contemporary multicenter cohort of preterm infants. Methods: We performed a retrospective analysis of data from a cluster-randomized controlled study. Infants <34 weeks of gestation and admitted to 25 neonatal intensive care units between May 1, 2015, and April 30, 2018, were included. Culture-negative LOS was diagnosed if infants had abnormal manifestations and laboratory tests but negative blood cultures. The primary outcome was a composite of mortality or morbidities including periventricular leukomalacia (PVL), retinopathy of prematurity (ROP) ≥ stage 3 or bronchopulmonary dysplasia (BPD). Results: Of 22,346 eligible infants, 1505 (6.7%) infants had culture-negative and 761 (3.4%) infants had culture-positive LOS. Compared with infants without LOS, infants with culture-negative LOS had higher rates of composite outcome (24.1% vs. 9.6%), death (3.8% vs. 1.8%), PVL (4.8% vs. 2.2%), severe ROP (3.3% vs. 1.1%) and BPD (18.1% vs. 7.0%). After adjustment, culture-negative LOS was independently associated with increased risk of composite outcome {adjusted odds ratio [aOR]: 1.8 [95% confidence interval (CI): 1.5–2.1]}, PVL [aOR: 2.0 (95% CI: 1.4–2.8)] and BPD [aOR: 1.8 (95% CI: 1.5–2.2)] relative to the absence of LOS. Conclusion: Culture-negative LOS was frequently diagnosed in preterm infants and was associated with increased risks of adverse outcomes. There is an emerging need for more precise diagnosis and treatment strategies for culture-negative LOS.

Among fetuses with PFA, those with cerebellar hypoplasia, vermis hypoplasia, or Dandy-Walker malformation are at the highest risk of clinically significant CNVs. Chromosomal microarray analysis revealed the most frequent chromosomal aberrations associated with CH.

Chromosomal mosaicism (CM) is a biological phenomenon defined as an individual who has arisen from a single zygote and has two or more populations of cells with distinct genotypes. 1 The main underlying mechanisms leading to mosaicism formation involve mitotic or meiotic non-disjunction errors, anaphase lagging and trisomy rescue, endoreplication events, and uniparental disomy (UPD) associated with trisomy rescue. 2 Theoretically, the pattern of the mosaic distribution in the foetus and placenta is largely determined by the