Impact of Brain Injury on Processing of Emotional Prosodies in Neonates

Being able to appropriately process different emotional prosodies is an important cognitive ability normally present at birth. In this study, we used event-related potential (ERP) to assess whether brain injury impacts the ability to process different emotional prosodies (happy, fear, and neutral) in neonates; whether the ERP measure has potential value for the evaluation of neurodevelopmental outcome in later childhood. A total of 42 full-term neonates were recruited from the neonatology department of Peking University First Hospital from June 2014 to January 2015. They were assigned to the brain injury group (n = 20) or control group (n = 22) according to their clinical manifestations, physical examinations, cranial images and routine EEG outcomes. Using an oddball paradigm, ERP data were recorded while subjects listened to happy (20%, deviation stimulus), fearful (20%, deviation stimulus) and neutral (80%, standard stimulus) prosodies to evaluate the potential prognostic value of ERP indexes for neurodevelopment at 30 months of age. Results showed that while the mismatch responses (MMRs) at the frontal lobe were larger for fearful than happy prosody in control neonates, this difference was not observed in neonates with brain injuries. This finding suggests that perinatal brain injury may influence the cognitive ability to process different emotional prosodies in neonatal brain; this deficit could be reflected by decreased MMR amplitudes in response to fearful prosody. Moreover, the decreased MMRs at the frontal lobe was associated with impaired neurodevelopment at 30 months old

Tigecycline application in a 3-month-old infant with multiple drug resistant Klebsiella pneumonia: a case report

Abstract Background Tigecycline is an ‘immature’ antibiotic for children. We report the youngest surviving patient who received a complete tigecycline treatment, and no significant adverse effects occurred in the patient. Case presentation The 3-month old infant suffered from a catheter-associated bloodstream infection by multiple drug resistant Klebsiella pneumoniae. Tigecycline was considered as a salvage therapy to control the severe sepsis. The therapy consisted of 3 mg/kg as a loading dose and 1.5 mg/kg Q12 h as a maintenance dose for 26 days. Conclusion Current researches are limited in clinical trials directly focused on children. This therapeutic schedule might be safe for patients who are above 3 months old

Discovery of Novel STING Inhibitors Based on the Structure of the Mouse STING Agonist DMXAA

The stimulator-of-interferon-gene (STING) protein is involved in innate immunity. The drug DMXAA (5,6-dimethylxanthenone-4-acetic acid) proved to be a potent murine-STING (mSTING) agonist but had little effect on human-STING (hSTING). In this paper, we draw upon the comparison of different crystal structures and protein-ligand interaction relationships analysis to venture the hypothesis that the drug design of DMXAA variants has the potential to convert STING agonists to inhibitors. Based on our previous discovery of two DMXAA analogs, 3 and 4 (both could bind to STING), we structurally optimized them and synthesized new derivatives, respectively. In binding assays, we found compounds 11 and 27 to represent STING binders that were superior to the original structures and discussed the structure-activity relationships. All target compounds were inactive in cellular assays for the screening of STING agonistic activity. Gratifyingly, we identified 11 and 27 as STING inhibitors with micromolar activity in both hSTING and mSTING pathways. In addition, 11 and 27 inhibited the induction of interferon and inflammatory cytokines activated by 2′3′-cGAMP without apparent cytotoxicity. These findings break the rigid thinking that DMXAA provides the structural basis specifically for STING agonists and open up more possibilities for developing novel STING agonists or inhibitors

MiR-144 Increases Intestinal Permeability in IBS-D Rats by Targeting OCLN and ZO1

Background/Aims: Irritable bowel syndrome with diarrhoea (IBS-D) is a chronic, functional bowel disorder characterized by abdominal pain or diarrhoea and altered bowel habits, which correlate with intestinal hyperpermeability. MicroRNAs (miRNAs) are involved in regulating intestinal permeability in IBS-D. However, the role of miRNAs in regulating intestinal permeability and protecting the epithelial barrier remains unclear. Our goals were to (i) identify differential expression of miRNAs and their targets in the distal colon of IBS-D rats; (ii) verify in vitro whether occludin (OCLN) and zonula occludens 1 (ZO1/TJP1) were direct targets of miR-144 and were down-regulated in IBS-D rats; and (iii) determine whether down-regulation of miR-144 in vitro could reverse the pathological hallmarks of intestinal hyperpermeability via targeting OCLN and ZO1. Methods: The IBS-D rat model was established using 4% acetic acid and evaluated by haematoxylin-eosin (HE) staining. The distal colon was obtained in order to perform miRNA microarray analysis and to isolate and culture colonic epithelial cells. When differential expression of miRNA was found, the results were verified by qRT-PCR, and the target genes were further explored by bioinformatics analysis. Correlation analyses were carried out to compare the expression of miRNA and target genes. Then, mutants, miRNA mimics and inhibitors of the target genes were constructed and transfected to colonic epithelial cells. qRT-PCR, western blotting, enzyme-linked immunosorbent assays (ELISAs) and dual-luciferase assays were used to investigate the expression of miR-144 and OCLN, ZO1 in IBS-D rats. Results: There were 8 up-regulated and 18 down-regulated miRNAs identified in the IBS-D rat model. Of these, miR-144 was markedly up-regulated and resulted in the down-regulation of OCLN and ZO1 expression. Overexpression of miR-144 by transfection of miR-144 precursor markedly inhibited the expression of OCLN and ZO1. Further studies confirmed that OCLN and ZO1 were direct targets of miR-144. Additionally, intestinal hyperpermeability was enhanced by miR-144 up-regulation and attenuated by miR-144 down-regulation in IBS-D rat colonic epithelial cells. Moreover, rescue experiments showed that overexpression of OCLN and ZO1 significantly eliminated the inhibitory effect of miR-144, which showed a stronger effect on the attenuation of intestinal hyperpermeability. Conclusion: Up-regulation of miR-144 could promote intestinal hyperpermeability and impair the protective effect of the epithelial barrier by directly targeting OCLN and ZO1. miR-144 is likely a key regulator of intestinal hyperpermeability and could be a potential therapeutic target for IBS-D

In vitro and in vivo studies on biodegradable magnesium alloy

The microstructure, mechanical property, electrochemical behavior and biocompatibility of magnesium alloy (BioDe MSM™) were studied in the present work. The experimental results demonstrated that grain refining induced by extrusion improves the alloy strength significantly from 162 MPa for the as-cast alloy to 241 MPa for the as-extruded one. The anticorrosion properties of the as-extruded alloy also increased. Furthermore, the hemolysis ratio was decreased from 4.7% for the as-cast alloy to 2.9% for the as-extruded one, both below 5%. BioDe MSM™ alloy shows good biocompatibility after being implanted into the dorsal muscle and the femoral shaft of the New Zealand rabbit, respectively, and there are no abnormalities after short-term implantation. In vivo observation indicated that the corrosion rate of this alloy varies with different implantation positions, with higher degradation rate in the femur than in the muscle

Retrospective analysis of the prognostic factors of fetal corpus callosum dysplasia

Abstract Background To analyze the genetic characteristics and long-term outcomes of fetuses with dysplasia of the corpus callosum (DCC) or partial agenesis of the corpus callosum (PACC). Methods A total of 42 fetuses with DCC (n = 36) or PACC (n = 6) were retrospectively analyzed from January 2016 to December 2022 at the Peking University First Hospital. The cohort was categorized into isolated (15/42, 36%) and nonisolated groups (27/42, 64%), and differences in the genetic abnormalities and long-term outcomes between the two groups were analyzed. DCC was subdivided into short CC, thin CC, and thick CC. The outcomes of the three different types of DCC were analyzed and discussed. Results (1) Thirty-nine of the 42 cases underwent CMA (chromosomal microarray analysis) and CMA + WES (whole exome sequencing), with 13/15 cases in isolated group and 26/27 cases in nonisolated group. Only pathogenic or likely pathogenic (P/LP) variants were considered, identifying P/LP variants in 2/13 cases in isolated group and 12/26 cases in nonisolated group. There was no significant difference between the two groups (χ² = 3.566, P = 0.05897). (2) In the isolated group, 8 cases were terminated, and 7 cases were delivered. Postnatal follow-up detected 1 case of gross motor development delay one year after birth; no obvious abnormalities were found in the other six cases. In the nonisolated group, 21 cases were terminated, and 6 cases were delivered. Postnatal follow-up detected 4 cases of children with different degrees of language, motor and intelligence abnormalities; 1 case died 10 days after birth. No obvious abnormalities were observed in one case. Six cases (86%, 6/7) in the isolated group showed normal development, compared with 1 case (17%, 1/6) in the nonisolated group, with a significant difference (χ² = 6.198, P = 0.01279). (3) In DCC, the delivery rates of short CCs (18 cases), thin CCs (13 cases), and thick CCs (5 cases) were 17% (3/18), 54% (7/13), and 20% (1/5), respectively, with good outcomes observed in 0% (0/3), 71% (5/7), and 0% (0/1), respectively. P/LP variants were found in 6/17 cases of short CC, 3/12 cases of thin CC, and 2/5 cases of thick CC. Conclusions Fetuses with DCC or PACC combined with other structural abnormalities had a poor long-term prognosis compared with the isolated group. Patients with thin CCs had a higher probability of a good prognosis than those with short or thick CCs

MOESM1 of Tigecycline application in a 3-month-old infant with multiple drug resistant Klebsiella pneumonia: a case report

Additional file 1: Table S1. Liver function. Table S2. Renal function. Table S3. Coagulation function

Combustion synthesis in the Ni–Al–Nb ternary system: A Time-Resolved X-ray Diffraction study

Combustion synthesis of intermetallics, using the thermal explosion mode, in the Ni-Al-Nb ternary system is presented, with a 40:40:20 atomic ratio. The kinetic pathway is determined using Time-Resolved X-ray Diffraction, with a time-step resolution of 1 s and demonstrated a first formation of the B2 NiAl structure followed by progressive dissolution of Nb to yield NiAlNb intermetallic Laves phase, representing 35 w% of the final product. SEM observations show a double dendritic (coarse and fine) microstructure, resulting from eutectic crystallization. Due to a high cooling rate, Nb dissolution is not complete at the surface, and yields slightly more complex microstructure, including the Ni2AlNb Geissler phase, the (Ni,Al)2Nb Laves phase, and (Ni, Al)7Nb6