Cathepsin B-Activatable Bioactive Peptide Nanocarrier for High-Efficiency Immunotherapy of Asthma.

Introduction: Asthma, a chronic respiratory disease closely associated with inflammation, presents ongoing treatment challenges. IALLIPF (le-Ala-Leu-Leu-Ile-Pro-Phe) is one of millet prolamins peptides (MPP) which shows anti-oxidant bioactivity by reducing the production of reactive oxygen species (ROS). Tryptophan (Trp, W) is an amino acid that has been demonstrated to possess anti-inflammatory effects. We introduce a novel cathepsin B-activatable bioactive peptides nanocarrier, PEG-IALLIPF-GFLG-W (MPP-Trp), designed for immunotherapy of asthma. Methods: MPP-Trp is synthesized, purified, and its characteristics are investigated by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The yield of nitric oxide (NO) and pro-inflammatory cytokines (TNF-α, IL-6 and IL-1ß) are examined to evaluate anti-inflammatory effects of IALLIPF, Trp and MPP-Trp. The immunomodulatory effects of IALLIPF, Trp and MPP-Trp on Th1/Th2 cell populations and cytokines are investigated by flow cytometry, qRT-PCR and ELISA assays. We explore the therapeutic effect of MPP-Trp in the mouse model of asthma by the analysis of lung histology and ELISA. It is necessary to study the biocompatibility of MPP-Trp by CCK8 assay and histopathologic analysis using hematoxylin and eosin (HE) staining. Results: In asthmatic peripheral blood mononuclear cells (PBMCs), IALLIPF, Trp and MPP-Trp are able to significantly alleviate inflammation by inhibiting the yield of nitric oxide (NO) and pro-inflammatory cytokines (TNF-α, IL-6 and IL-1ß), especially MPP-Trp. MPP-Trp significantly upregulates Th1 cell levels while notably reducing Th2 cell levels. Furthermore, MPP-Trp effectively elevates the expression and production of interferon-gamma (IFN-γ), an essential cytokine from Th1 cells. Additionally, MPP-Trp markedly diminishes the mRNA expression and levels of key asthma pathogenesis cytokines, such as interleukin-4 (IL-4), interleukin-13 (IL-13), and interleukin-5 (IL-5), in asthma PBMCs. MPP-Trp ameliorates pulmonary pathological alterations and significantly inhibits OVA-induced inflammation in mice with asthma. It has little influence on the cell viability in Asthma-PBMCs treated with various concentrations or durations of MPP-Trp. No pathological changes, including in the heart, liver, spleen, lung, and kidney tissues, are observed in non-sensitized and non-challenged mice treated with MPP-Trp (20 mg/kg). Discussion: Our research demonstrates that MPP-Trp has immunomodulatory effects on Th1/Th2 cell populations, essential in managing asthma. It considerably alleviates OVA-induced asthma by shifting the immune response towards a Th1-dominant profile, thereby reducing Th2-driven inflammation. Therefore, this novel bioactive peptide nanocarrier, MPP-Trp, holds promise as a candidate for asthma immunotherapy.

[Impact of different angles of pulmonary surfactant administration on bronchopulmonaryplasia and intracranial hemorrhage in preterm infants: a prospective randomized controlled study]. / ä¸åŒè§’åº¦æ³¨å ¥è‚ºè¡¨é¢æ´»æ€§ç‰©è´¨å¯¹æ—©äº§å„¿æ”¯æ°”ç®¡è‚ºå‘è‚²ä¸è‰¯å’Œé¢ å† å‡ºè¡€çš„å½±å“ï¼šä¸€é¡¹å‰çž»æ€§éšæœºå¯¹ç §ç ”ç©¶.

OBJECTIVES: To investigate the effects of different angles of pulmonary surfactant (PS) administration on the incidence of bronchopulmonary dysplasia and intracranial hemorrhage in preterm infants. METHODS: A prospective study was conducted on 146 preterm infants (gestational age <32 weeks) admitted to the Department of Neonatology, Provincial Hospital Affiliated to Anhui Medical University from January 2019 to May 2023. The infants were randomly assigned to different angles for injection of pulmonary surfactant groups: 0° group (34 cases), 30° group (36 cases), 45° group (38 cases), and 60° group (38 cases). Clinical indicators and outcomes were compared among the groups. RESULTS: The oxygenation index was lower in the 60° group compared with the other three groups, with shorter invasive ventilation time and oxygen use time, and a lower incidence of bronchopulmonary dysplasia than the other three groups (P<0.05). The incidence of intracranial hemorrhage was lower in the 60° group compared to the 0° group (P<0.05). The cure rate in the 60° group was higher than that in the 0° group and the 30° group (P<0.05). CONCLUSIONS: The clinical efficacy of injection of pulmonary surfactant at a 60° angle is higher than other angles, reducing the incidence of intracranial hemorrhage and bronchopulmonary dysplasia in preterm infants.

Steganographic optical image encryption based on single-pixel imaging and an untrained neural network.

We propose a steganographic optical image encryption based on single-pixel imaging (SPI) and an untrained neural network. In this encryption scheme, random binary illumination patterns are projected onto a secret image and light intensities reflected from the image are then detected by a bucket detector (BD). To enhance the security of collected secret data, a steganographic approach is introduced in this method, which implements data hiding with a SPI system using encoded illumination patterns. A non-secret image is illuminated with a sequence of encoded patterns that were generated from the scrambled measurements of secret image, and sequential cyphertext data can be obtained by collecting the diffraction data with the BD. Different from traditional SPI-based encryption schemes, an untrained neural network is adopted as a SPI-encrypted image processor, which allows to reduce time spent on data preparation and reconstruct the secret images with high quality. Both computer simulations and optical experiments are carried out to demonstrate the feasibility of the method.

Hypoperfusion With Vomiting, Abdominal Pain, or Dizziness and Convulsions: An Alert to Fulminant Myocarditis in Children.

Objective: To investigate the clinical features, treatment methods, and outcomes of fulminant myocarditis (FM) in children. Methods: The clinical data of 23 children with FM hospitalized in the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China (Anhui Provincial Hospital) and Anhui Provincial Children's Hospital from January 2011 to September 2019 were retrospectively analyzed. Results: Among the 23 patients analyzed, 10 were male and 13 were female. The patients aged from 6 months to 14 years old (6.5 ± 3.4 years), and 18 patients were over 3 years old. There were 14 cases with respiratory symptoms, 16 cases with gastrointestinal symptoms, 15 cases with neurological symptoms, and 19 cases with hypoperfusion manifestations. Creatine kinase MB (CK-MB) and cardiac troponin I (CTnI) levels were increased in 19 and 21 cases, respectively. Electrocardiography (ECG) showed ST-T changes in 18 cases and atrioventricular blocks (AVB) in 15 cases. Echocardiography (ECHO) showed cardiac chamber enlargement (CCE) in eight cases, left ventricular systolic dysfunction in five cases, decrease in left ventricular ejection fraction (LVEF) in four cases, reduction in wall motion in two cases, and pericardial effusion in seven cases. Intravenous immunoglobulin (IVIG) and glucocorticoids were administered to 19 and 20 patients, respectively. Fourteen patients were treated with temporary pacemakers, one patient received extracorporeal membrane oxygenation (ECMO), one patient received continuous renal replacement therapy (CRRT), and one patient received ECMO combined with CRRT. Twenty patients improved at discharge, and three patients died. Conclusion: Preschool and school-age children showing hypoperfusion symptoms, such as paleness, cold, clammy limbs, and capillary refill time (CRT) extension, accompanied by vomiting, abdominal pain, dizziness, convulsions, and other symptoms, should be carefully examined for FM. CK-MB, CTnI, ECG, and echocardiogram need to be performed at the earliest opportunity. In the early stages of FM, vital signs should be actively monitored, high-dose IVIG and glucocorticoids should be administered, and life support technologies such as temporary pacemakers, ECMO, and CRRT should be used to increase the survival rate of children with FM as needed.

Novel mutation of SCN9A gene causing generalized epilepsy with febrile seizures plus in a Chinese family.

Generalized epilepsy with febrile seizures plus (GEFS+) is a complex familial epilepsy syndrome. It is mainly caused by mutations in SCN1A gene, encoding type 1 voltage-gated sodium channel α-subunit (NaV1.1), and GABRA1 gene, encoding the α1 subunit of the γ-aminobutyric acid type A (GABAA) receptor, while seldom related with SCN9A gene, encoding the voltage-gated sodium channel NaV1.7. In this study, we investigated a Chinese family with an autosomal dominant form of GEFS+. DNA sequencing of the whole coding region revealed a novel heterozygous nucleotide substitution (c.5873A>G) causing a missense mutation (p.Y1958C). This mutation was predicted to be deleterious by three different bioinformatics programs (The polyphen2, SIFT, and MutationTaster). Our finding reports a novel likely pathogenic SCN9A Y1958C heterozygous mutation in a Chinese family with GEFS+ and provides additional supports that SCN9A variants may be associated with human epilepsies.