Virus classification for viral genomic fragments using PhaGCN2.

Viruses are the most ubiquitous and diverse entities in the biome. Due to the rapid growth of newly identified viruses, there is an urgent need for accurate and comprehensive virus classification, particularly for novel viruses. Here, we present PhaGCN2, which can rapidly classify the taxonomy of viral sequences at the family level and supports the visualization of the associations of all families. We evaluate the performance of PhaGCN2 and compare it with the state-of-the-art virus classification tools, such as vConTACT2, CAT and VPF-Class, using the widely accepted metrics. The results show that PhaGCN2 largely improves the precision and recall of virus classification, increases the number of classifiable virus sequences in the Global Ocean Virome dataset (v2.0) by four times and classifies more than 90% of the Gut Phage Database. PhaGCN2 makes it possible to conduct high-throughput and automatic expansion of the database of the International Committee on Taxonomy of Viruses. The source code is freely available at https://github.com/KennthShang/PhaGCN2.0.

SHORT-ROOT paralogs mediate feedforward regulation of D-type cyclin to promote nodule formation in soybean.

Nitrogen fixation in soybean takes place in root nodules that arise from de novo cell divisions in the root cortex. Although several early nodulin genes have been identified, the mechanism behind the stimulation of cortical cell division during nodulation has not been fully resolved. Here we provide evidence that two paralogs of soybean SHORT-ROOT (GmSHR) play vital roles in soybean nodulation. Expression of GmSHR4 and GmSHR5 (GmSHR4/5) is induced in cortical cells at the beginning of nodulation, when the first cell divisions occur. The expression level of GmSHR4/5 is positively associated with cortical cell division and nodulation. Knockdown of GmSHR5 inhibits cell division in outer cortical layers during nodulation. Knockdown of both paralogs disrupts the cell division throughout the cortex, resulting in poorly organized nodule primordia with delayed vascular tissue formation. GmSHR4/5 function by enhancing cytokinin signaling and activating early nodulin genes. Interestingly, D-type cyclins act downstream of GmSHR4/5, and GmSHR4/5 form a feedforward loop regulating D-type cyclins. Overexpression of D-type cyclins in soybean roots also enhanced nodulation. Collectively, we conclude that the GmSHR4/5-mediated pathway represents a vital module that triggers cytokinin signaling and activates D-type cyclins during nodulation in soybean.

Cold stress induces malformed tomato fruits by breaking the feedback loops of stem cell regulation in floral meristem.

Fruit malformation is a major constrain in fruit production worldwide resulting in substantial economic losses. The farmers for decades noticed that the chilling temperature before blooming often caused malformed fruits. However, the molecular mechanism underlying this phenomenon is unclear. Here we examined the fruit development in response to cold stress in tomato, and demonstrated that short-term cold stress increased the callose accumulation in both shoot apical and floral meristems, resulting in the symplastic isolation and altered intercellular movement of WUS. In contrast to the rapidly restored SlWUS transcription during the recovery from cold stress, the callose removal was delayed due to obstructed plasmodesmata. The delayed reinstatement of cell-to-cell transport of SlWUS prevented the activation of SlCLV3 and TAG1, causing the interrupted feedback inhibition of SlWUS expression, leading to the expanded stem cell population and malformed fruits. We further showed that the callose dynamics in response to short-term cold stress presumably exploits the mechanism of bud dormancy during the seasonal growth, involving two antagonistic hormones, abscisic acid and gibberellin. Our results provide a novel insight into the cold stress regulated malformation of fruit.

The MIO1-MtKIX8 module regulates the organ size in Medicago truncatula.

Plant organ size is an important agronomic trait tightly related to crop yield. However, the molecular mechanisms underlying organ size regulation remain largely unexplored in legumes. We previously characterized a key regulator F-box protein MINI ORGAN1 (MIO1)/SMALL LEAF AND BUSHY1 (SLB1), which controls plant organ size in the model legume Medicago truncatula. In order to further dissect the molecular mechanism, MIO1 was used as the bait to screen its interacting proteins from a yeast library. Subsequently, a KIX protein, designated MtKIX8, was identified from the candidate list. The interaction between MIO1 and MtKIX8 was confirmed further by Y2H, BiFC, split-luciferase complementation and pull-down assays. Phylogenetic analyses indicated that MtKIX8 is highly homologous to Arabidopsis KIX8, which negatively regulates organ size. Moreover, loss-of-function of MtKIX8 led to enlarged leaves and seeds, while ectopic expression of MtKIX8 in Arabidopsis resulted in decreased cotyledon area and seed weight. Quantitative reverse-transcription PCR and in situ hybridization showed that MtKIX8 is expressed in most developing organs. We also found that MtKIX8 serves as a crucial molecular adaptor, facilitating interactions with BIG SEEDS1 (BS1) and MtTOPLESS (MtTPL) proteins in M. truncatula. Overall, our results suggest that the MIO1-MtKIX8 module plays a significant and conserved role in the regulation of plant organ size. This module could be a good target for molecular breeding in legume crops and forages.

NCX2 Regulates Intracellular Calcium Homeostasis and Translocation of HIF-1α into the Nucleus to Inhibit Glioma Invasion.

Glioma is the most common tumor of the central nervous system, and its poor prognosis can be linked to hypoxia and gene inactivation. Na+/Ca2+ exchanger 2 (NCX2) is expressed only in the normal brain and not in other tissues or glioma. We constructed a hypoxic microenvironment to more accurately understand the effect of NCX2 in glioma. Our previous experiments confirmed that NCX2 inhibited the growth of U87 cells in nude mice, indicating that NCX2 is a potential tumor suppressor gene. Malignant tumor cells are often exposed to an anoxic environment. To more accurately understand the effect of NCX2 in glioma, we constructed a hypoxic microenvironment. To detect the localization of NCX2 in transfected U87 cells, immunofluorescence was used. We tested the function of NCX2 in glioma, i.e., how it contributes to the cytosolic Ca2+ homeostasis by X-Rhod-1. We tested the cell proliferation of NCX2 in glioma in hypoxic using Cell counting kit-8 (CCK8). Cell migration and invasion were evaluated in 24-well transwell matrigel-coated or non-matrigel-coated in hypoxia. NCX2 promoted the proliferation of U87 cells in the hypoxic microenvironment. It inhibited the invasion and migration abilities of U87 cells. We demonstrated that NCX2 was located on the cell membrane and that it reduced intracellular Ca2+ levels and reactivated P53 and PTEN. We further demonstrated that NCX2 impaired cell invasion through the HIF-1α pathway in glioma. The results indicated that NCX2 plays a key role in glioma formation and tumor invasion functionality.

Age and sex differences in social support among children and adolescents with epilepsy.

OBJECTIVE: This study aimed to explore what differences exist in the perceived frequency of social support and the importance of social support according to age and sex among children and adolescents with epilepsy. METHOD: We employed an explorative cross-sectional design to examine a sample of 320 children and adolescents with epilepsy using the child and adolescent social support scale (CASSS). RESULT: There is a significant relationship between sex and age and the importance of support from classmates and friends. For the dependent variables that were not affected by the age-sex interaction, we analyzed the main effects of these dependent variables of sex and age separately. We discovered that girls with epilepsy received a higher level of support from their parents and classmates than boys. Besides, compared with adolescents, children with epilepsy consider parental support more valuable. Also, children with epilepsy attach more importance to support from their teachers than adolescents. In contrast, adolescents with epilepsy receive a higher level of support from their friends than children. CONCLUSION: Social support varies by age and sex in children and adolescents with epilepsy. Understanding the social support of children with epilepsy at various developmental stages and for different sexes can help provide a healthier environment for children and adolescents to grow up in. The results of this study provide a basis for formulating corresponding intervention programs for children and adolescents with epilepsy according to age and sex.

The Chinese version of the Quality of Life in Childhood Epilepsy Questionnaire-16-C (QOLCE-16-C): translation, validity, and reliability.

BACKGROUND: Epilepsy is one of the most common chronic neurological diseases that adversely impact the quality of life of patients and their families. The "Quality of Life of Childhood Epilepsy Questionnaire" (hereinafter referred to as "QOLCE-16") is a 16-item measure that was designed to assess health-related quality of life (HRQOL) among children with epilepsy. The purpose of the study was to translate and evaluate the psychometric properties of the QOLCE-16. METHODS: The 10 steps of Principles of Good Practices for translation and cultural adaptation of measures were adopted to translate the QOLCE-16 into Chinese. After that, item analysis, floor effect and ceiling effect, internal consistency, test-retest reliabilities, content validity and construct validity were conducted to test its applicability in children with epilepsy in China. A total of 435 native Chinese-speaking parents with children who had epilepsy from one children's hospital were invited to take part in the study, including a cognitive interview sample of 5 and a validation sample of 430. RESULTS: A total of 414 objects were enrolled in our study for psychometric testing. The results of the item analysis revealed QOLCE-16-C to have good discrimination, the floor effect and ceiling effect were 0.2% and 1.0% respectively, and each item was significantly related to the total scale (P < 0.001). The Cronbach's α value was 0.938 and the test-retest reliability was 0.724. For validity, results showed that the QOLCE-16-C had good content validity. Exploratory factor analysis indicated it was reasonable that the QOLCE-16-C consists of four dimensions after rotation. Confirmatory factor analysis demonstrated good construct validity (χ2/df = 1.698, GFI = 0.913, CFI = 0.974, RMSEA = 0.058). CONCLUSION: The Chinese version of QOLCE-16-C appears to be a culturally appropriate, valid and reliable tool to assess the health-related quality of life of children with epilepsy in China.

Histological assessment based on liver biopsy: the value and challenges in NASH drug development.

Nonalcoholic steatohepatitis (NASH) is increasingly recognized as a serious disease that can lead to cirrhosis, hepatocellular carcinoma (HCC), and death. However, there is no effective drug to thwart the progression of the disease. Development of new drugs for NASH is an urgent clinical need. Liver biopsy plays a key role in the development of new NASH drugs. Histological findings based on liver biopsy are currently used as the main inclusion criteria and the primary therapeutic endpoint in NASH clinical trials. However, there are inherent challenges in the use of liver biopsy in clinical trials, such as evaluation reliability, sampling error, and invasive nature of the procedure. In this article, we review the advantages and value of liver histopathology based on liver biopsy in clinical trials of new NASH drugs. We also discuss the challenges and limitations of liver biopsy and identify future drug development directions.

Fulminant Guillain-Barré syndrome developed after surgical treatment of intracranial hemorrhage due to arteriovenous malformation: a case report.

Guillain-Barré syndrome (GBS) is a rare autoimmune disorder. GBS after surgical treatment of intracranial hemorrhage due to arteriovenous malformation (AVM) is even rarer. We present a 62-year-old man diagnosed with intracranial AVM and cerebral hemorrhage. He developed GBS after the operation for AVM and cerebral hemorrhage. Following surgical excision of AVM and cerebral hematoma, the patient developed generalized weakness, with subsequent quadriplegia and life-threatening dyspnea. The diagnosis was confirmed to be the acute motor-sensory axonal neuropathy subtype of GBS after cerebrospinal fluid analysis and antibody tests. The patient responded poorly to immunoglobulin and steroid therapy. His family abandoned further management and signed out of the hospital against medical advice. Despite being rare, GBS can occur after intracranial hemorrhage and surgery. Clinicians should rule out GBS when patients show no improvement or develop new neurologic.

Parental experience of transition from a paediatric intensive care unit to a general ward: A qualitative study.

AIM: We aim to explore parental experience in transitioning from a paediatric intensive care unit to a general ward and to investigate parental involvement in caring for their critical illness children. BACKGROUND: Parents have a major responsibility in caring for seriously ill children, but nursing staff fail to meet the expectations of parents regarding nursing care. Few studies have investigated the challenges and needs of Chinese parents during the transition from paediatric intensive care unit to general ward. METHODS: Semi-structured interviews were conducted with 24 parents of children with critical illness in a paediatric hospital in Shanghai, mainland China to explore their views. Transcripts were entered into NVivo. Framework analysis was used to analyse the qualitative data. RESULTS: Four themes were identified by data analysis: changes in the child during post paediatric intensive care unit periods; experiencing a wide range of emotions; factors involved in the transition; and suggestions for improving transitional care. CONCLUSIONS: Due to the unmet needs of parents, a more flexible visiting policy and social media support were highly desirable. Getting accurate information, establishing family integrated care, and strengthening ward-based critical support services were also listed as important needs of parents caring for critically ill children. IMPLICATIONS FOR NURSING MANAGEMENT: A profound understanding of parental experiences during the transitional period can help nursing staff to assess the effects on children and their families, improve ward-based intensive care, support parental participation, and improve visitation policies. Based on these findings, nurse managers can develop reasonable intervention programmes in order to improve nursing quality and patient outcomes.

Nursing perspectives on transitional care between paediatric intensive care units and general wards: A focus group study.

AIM: We aim to explore the experiences of nursing staff in paediatric intensive care units (PICUs) and wards when transporting and caring for patients being discharged from PICU. BACKGROUND: PICU discharge is a challenging and complex procedure with risks and complications for patients. Nursing staff in PICU and paediatric wards play a pivotal role in the transition and are responsible for the quality of care, but their perspectives have rarely been explored. METHODS: Focus groups were conducted between December 2021 and January 2022 with purposively sampled PICU nurses and ward nurses. Four focus groups were formed, and data were analysed using qualitative content analysis. RESULTS: The overarching themes were as follows: communication during handover, attitudes towards follow-up, a challenging transition for nurses and parents and suggestions for optimizing transitional procedure. CONCLUSION: Our findings provide nurses' insights and knowledge regarding the transition of patients from the PICU to the ward. Nursing strategies including the use of liaison nurses and critical training for ward nurses were considered essential to maintaining competence during transition. A well-structured handover checklist as well as interdisciplinary cooperation and transitional care units are important for the patient's quality of care. IMPLICATION FOR NURSING MANAGEMENT: Communication, cooperation, planning and professional care are vital during the transition process. Nurse managers should work to develop collaborative approaches to facilitate safe patient transition.

Teachers' experiences of managing children with epilepsy in school: A qualitative study.

BACKGROUND: School is the second most important environment for children second to the family. An increasing number of children with epilepsy (CWE) are able to go back to school to continue to study after treatment. In school, CWE can be involved in studies and activities, which is conducive to their growth. However, CWE have to face more barriers than other children in school, such as cognitive impairment, poor attendance, school absenteeism, and learning disability. What is more, even if CWE have been taking antiepileptic medicines, they still have a risk of seizure. Therefore, it is important to ensure the safety of CWE in the school. Teachers play a significant part in managing CWE in school, so we aimed to deeply explore the experiences of school teachers in managing CWE during school. METHOD: Purposive sampling was used to recruit teachers (n = 17) who cared for children with epilepsy in their class. Semi-structured interviews were used to access qualitative data. Framework analysis was used to analyze qualitative data. RESULT: Five major themes emerged after analyzing: the recognition of epilepsy, the attitude to children with epilepsy, the barriers to communicate with parents about epilepsy, the reaction to a seizure, and the need for training. CONCLUSION: The findings of this qualitative study reported teachers' knowledge of and attitude toward epilepsy, the barriers for them to communicate with parents, the reaction to seizure, and the need for training. Although teachers know little about epilepsy, they have a positive attitude toward CWE. There are many obstacles in terms of the communication between teachers and parents. Parents' cover-ups and teachers' lack of professional training will put teachers and CWE at risk. In view of the fact that teachers and parents are not professionals, it is necessary for hospitals to play a coordinating role between the two.

SlGT11 controls floral organ patterning and floral determinacy in tomato.

BACKGROUND: Flower development directly affects fruit production in tomato. Despite the framework mediated by ABC genes have been established in Arabidopsis, the spatiotemporal precision of floral development in tomato has not been well examined. RESULTS: Here, we analyzed a novel tomato stamenless like flower (slf) mutant in which the development of stamens and carpels is disturbed, with carpelloid structure formed in the third whorl and ectopic formation of floral and shoot apical meristem in the fourth whorl. Using bulked segregant analysis (BSA), we assigned the causal mutation to the gene Solanum lycopersicum GT11 (SlGT11) that encodes a transcription factor belonging to Trihelix gene family. SlGT11 is expressed in the early stages of the flower and the expression becomes more specific to the primordium position corresponding to stamens and carpels in later stages of the floral development. Further RNAi silencing of SlGT11 verifies the defective phenotypes of the slf mutant. The carpelloid stamen in slf mutant indicates that SlGT11 is required for B-function activity in the third whorl. The failed termination of floral meristem and the occurrence of floral reversion in slf indicate that part of the C-function requires SlGT11 activity in the fourth whorl. Furthermore, we find that at higher temperature, the defects of slf mutant are substantially enhanced, with petals transformed into sepals, all stamens disappeared, and the frequency of ectopic shoot/floral meristem in fourth whorl increased, indicating that SlGT11 functions in the development of the three inner floral whorls. Consistent with the observed phenotypes, it was found that B, C and an E-type MADS-box genes were in part down regulated in slf mutants. CONCLUSIONS: Together with the spatiotemporal expression pattern, we suggest that SlGT11 functions in floral organ patterning and maintenance of floral determinacy in tomato.

Characterization of the active fragments of Spodoptera litura Lebocin-1.

Insects can produce various antimicrobial peptides (AMPs) upon immune stimulation. One class of AMPs are characterized by their high proline content in certain fragments. They are generally called proline-rich antimicrobial peptides (PrAMPs). We previously reported the characterization of Spodoptera litura lebocin-1 (SlLeb-1), a PrAMP proprotein. Preliminary studies with synthetic polypeptides showed that among the four deductive active fragments, the C-terminal fragment SlLeb-1 (124-158) showed strong antibacterial activities. Here, we further characterized the antibacterial and antifungal activities of 124-158 and its four subfragments: 124-155, 124-149, 127-158, and 135-158. Only 124-158 and 127-158 could agglutinate bacteria, while 124-158 and four subfragments all could agglutinate Beauveria bassiana spores. Confocal microscopy showed that fluorescent peptides were located on the microbial surface. Fragment 135-158 lost activity completely against Escherichia coli and Staphylococcus aureus, and partially against Bacillus subtilis. Only 124-149 showed low activity against Serratia marcescens. Negative staining, transmission, and scanning electron microscopy of 124-158 treated bacteria showed different morphologies. Flow cytometry analysis of S. aureus showed that 124-158 and four subfragments changed bacterial subpopulations and caused an increase of DNA content. These results indicate that active fragments of SlLeb-1 may have diverse antimicrobial effects against different microbes. This study may provide an insight into the development of novel antimicrobial agents.

Protective Effect of Phillyrin on Lethal LPS-Induced Neutrophil Inflammation in Zebrafish.

BACKGROUND/AIMS: Forsythia suspensa Vahl. (Oleaceae) fruits are widely used in traditional Chinese medicine to treat pneumonia, typhoid, dysentery, ulcers and oedema. Antibacterial and anti-inflammatory activities have been reported for phillyrin (PHN), the main ingredient in Forsythia suspensa Vahl fruits, in vitro. However, the underlying mechanisms in vivo remain poorly defined. In this study, we discovered that PHN exerted potent anti-inflammatory effects in lethal LPS-induced neutrophil inflammation by suppressing the MyD88-dependent signalling pathway in zebrafish. METHODS: LPS-yolk microinjection was used to induce a lethal LPS-infected zebrafish model. The effect of PHN on the survival of zebrafish challenged with lethal LPS was evaluated using survival analysis. The effect of PHN on neutrophil inflammation grading in vivo was assessed by tracking neutrophils with a transgenic line. The effects of PHN on neutrophil production and migration were analysed by SB+ cell counts during consecutive hours after modelling. Additionally, key cytokines and members of the MyD88 signalling pathway that are involved in inflammatory response were detected using quantitative RT-PCR. To assess gene expression changes during consecutive hours after modelling, the IL-1ß, IL-6, TNF-α, MyD88, TRIF, ERK1/2, JNK, IκBa and NF-κB expression levels were measured. RESULTS: PHN could protect zebrafish against a lethal LPS challenge in a dose-dependent manner, as indicated by decreased neutrophil infltration, reduced tissue necrosis and increased survival rates. Up-regulated IL-1ß, IL-6 and TNF-α expression also showed the same tendencies of depression by PHN. Critically, PHN significantly inhibited the LPS-induced activation of MyD88, IκBa, and NF-κB but did not affect the expression of ERK1/2 MAPKs or JNK MAPKs in LPS-stimulated zebrafish. Additionally, PHN regulated the MyD88/IκBα/NF-κB signalling pathway by controlling IκBα, IL-1ß, IL-6, and TNF-α expression. CONCLUSION: This study provides a rationale for the clinical application of PHN as an anti-inflammatory agent.

Insulin Attenuates Beta-Amyloid-Associated Insulin/Akt/EAAT Signaling Perturbations in Human Astrocytes.

The excitatory amino acid transporters 1 and 2 (EAAT1 and EAAT2), mostly located on astrocytes, are the main mediators for glutamate clearance in humans. Malfunctions of these transporters may lead to excessive glutamate accumulation and subsequent excitotoxicity to neurons, which has been implicated in many kinds of neurodegenerative disorders including Alzheimer's disease (AD). Yet, the specific mechanism of the glutamate system dysregulation remains vague. To explore whether the insulin/protein kinase B (Akt)/EAAT signaling in human astrocytes could be disturbed by beta-amyloid protein (Aß) and be protected by insulin, we incubated HA-1800 cells with varying concentrations of Aß1-42 oligomers and insulin. Then the alterations of several key substrates in this signal transduction pathway were determined. Our results showed that expressions of insulin receptor, phospho-insulin receptor, phospho-protein kinase B, phospho-mammalian target of rapamycin, and EAAT1 and EAAT2 were decreased by the Aß1-42 oligomers in a dose-dependent manner (p < 0.05) and this trend could be recovered by insulin treatment (p < 0.05). However, the expressions of total Akt and mTOR were invariant (p > 0.05), and the mRNA levels of EAAT1 and EAAT2 were also unchanged (p > 0.05). Taken together, this study indicates that Aß1-42 oligomers could cause disturbances in insulin/Akt/EAAT signaling in astrocytes, which might be responsible for AD onset and progression. Additionally, insulin can exert protective functions to the brain by modulating protein modifications or expressions.

Thermal death kinetics of fifth-instar Corcyras cephalonica (Lepidoptera: Galleriidae).

The infestation of rice moth, Corcyras cephalonica (Lepidoptera: Galleriidae), causes severe losses in postharvest walnuts. Heat has been studied as a phytosanitary treatment to replace chemical fumigation for controlling this pest. Information on kinetics for thermal mortality of C. cephalonica is needed for developing effective postharvest phytosanitary thermal treatments of walnuts. Thermal death kinetics of fifth-instar C. cephalonica were investigated at temperatures between 44°C and 50°C at a heating rate of 5°C min(-1) using a heating block system. The results showed that thermal-death curves for C. cephalonica larvae followed a 0 order of kinetic reaction. The time to reach 100% mortality decreased with increasing temperature from 150 min at 44°C to 2.5 min at 50°C. The activation energy for controlling C. cephalonica was 466-592 kJ/mol, and the z value obtained from the thermal death time curve was 3.3°C. This kinetic model prediction could be useful in designing the thermal treatment protocol for controlling C. cephalonica in walnuts.

Endotoxin molecule lipopolysaccharide-induced zebrafish inflammation model: a novel screening method for anti-inflammatory drugs.

Lipopolysaccharide (LPS), an endotoxin molecule, has been used to induce inflammatory responses. In this study, LPS was used to establish an in vivo inflammation model in zebrafish for drug screening. We present an experimental method that conveniently and rapidly assesses the anti-inflammatory properties of drugs. The yolks of 3-day post-fertilization (dpf) larvae were injected with 0.5 mg/mL LPS to induce fatal inflammation. After LPS stimulation, macrophages were tracked by NR and SB staining and neutrophil migration was observed using the MPO:GFP line. Larval mortality was used as the primary end-point. Expression levels of key cytokines involved in the inflammatory response including IL-1ß, IL-6, and TNF-α, were measured using quantitative reverse transcription polymerase chain reaction (RT-PCR). Macrophages and neutrophils were both recruited to the LPS-injected site during the inflammatory response. Mortality was increased by LPS in a dose-dependent manner within 48 h. Analyses of IL-1ß, IL-6, and TNF-α expression levels revealed the upregulation of the inflammatory response in the LPS-injected larvae. Further, the anti-inflammatory activity of chlorogenic acid (CA) was evaluated in this zebrafish model to screen for anti-inflammatory drugs. A preliminary result showed that CA revealed a similar effect as the corticosteroid dexamethasone (DEX), which was used as a positive control, by inhibiting macrophage and neutrophil recruitment to the LPS site and improving survival. Our results suggest that this zebrafish screening model could be applied to study inflammation-mediated diseases. Moreover, the Traditional Chinese Medicine CA displays potential anti-inflammatory activity.

Pediatricians' Perspectives on Introducing Transitional Care into Handover Between Pediatric Intensive Care Units and General Wards.

Background: Despite the availability of a considerable number of studies on transitional care, few qualitative studies have synthesized physicians' perspectives on PICU-to-ward transition to develop a comprehensive transitional care curriculum. The aim of this study is to explore physicians' perceptions and management of the transition of critically ill children from the PICU to the general ward, with the aim of providing an evidence-based curriculum. Methods: A qualitative study was conducted between July and August 2022. The study involved semi-structured interviews with 11 participants, and data analysis was carried out using NVivo 12.0 software through thematic analysis method. Results: Based on the data analysis, three main themes were identified: recognition of professional roles during transition, difficulties during implementation transitional care and suggestions for improving transitional care. Conclusion: The insights of doctors can be valuable in improving transitional care for critically ill children during PICU-to-Ward transition and in developing relevant curricula. It is essential to introduce standardized clinical pathways and strengthen curricula on critical elements, including communication and follow-up.

Cord blood stem cell­derived Angptl7 ameliorates the severity of bronchopulmonary dysplasia via anti­inflammatory and proangiogenic effects.

Perinatal exposure of the neonatal lung to inflammation leads to decreased lung angiogenesis and the development of bronchopulmonary dysplasia (BPD). Notably, autologous cord blood mononuclear cells (ACBMNCs) can substantially prevent severe BPD and decrease the inflammatory response in surviving very preterm neonates. Angiopoietin­like protein 7 (Angptl7) is one of the main paracrine cytokines in cord blood stem cells, and is capable of stimulating human hematopoietic stem and progenitor cell expansion. The present study compared Angptl7 levels between the ACBMNCs infusion and control groups (cohort 1). Subsequently, the association between cord blood Angptl7 levels and BPD incidence in a cohort of very preterm neonates was assessed (cohort 2). The hypothesis was further verified in a lipopolysaccharide (LPS)­induced lung injury mouse model. The mRNA expression levels and protein concentrations of inflammatory cytokines in the lung tissue and mouse serum were measured using reverse transcription­quantitative PCR and ELISA, respectively. The number and diameter of lung vessels and macrophage infiltration were assessed using immunofluorescence staining. Compared with in the control group, Angptl7 levels were significantly higher in the ACBMNCs infusion group in cohort 1. In cohort 2, the cord blood Angptl7 levels were significantly lower in infants who later developed BPD. Multiple linear regression analysis showed that higher Angptl7 level was an independent protective factor for BPD. The concentrations of interleukin­6 and monocyte chemoattractant protein­1 were negatively correlated with cord blood Angptl7 level; whereas, vascular endothelial growth factor­A levels were positively correlated with Angptl7 levels. In the LPS­induced lung injury mouse model, the LPS group presented with a significant loss of pulmonary vessels and smaller vessel diameters, which were ameliorated in the Angptl7 treatment group. Furthermore, LPS­induced lung inflammation and macrophage infiltration were alleviated by Angptl7 treatment (P<0.05). In conclusion, the anti­inflammatory and proangiogenic effects of Angptl7 derived from cord blood stem cells may ameliorate BPD severity. The trial for cohort 1 was registered at ClinicalTrials.gov (trial registration no. NCT02999373; date registered, December 21, 2016).