Exploration of N6-methyladenosine modification in ascorbic acid 2-glucoside constructed stem cell sheets.

The aim of this study was to explore the mechanism of bone marrow stem cells (BMSCs) sheets constructed with different doses of Ascorbic acid 2-glucoside (AA-2G) in conjunction with N6-methyladenosine (m6A)-associated epigenetic genes analysing transcriptome sequencing data. Experimental groups of BMSCs induced by different AA-2G concentrations were set up, and the tissue structures were observed by histological staining of cell slices and scanning electron microscopy. Expression patterns of DEGs were analysed using short-time sequence expression mining software, and DEGs associated with m6A were selected for gene ontology analysis and pathway analysis. The protein-protein interaction (PPI) network of DEGs was analysed and gene functions were predicted using the search tool of the Retrieve Interacting Genes database. There were 464 up-regulated DEGs and 303 down-regulated DEGs between the control and high-dose AA-2G treatment groups, and 175 up-regulated DEGs and 37 down-regulated DEGs between the low and high-dose AA-2G treatment groups. The profile 7 exhibited a gradual increase in gene expression levels over AA-2G concentration. In contrast, profile 0 exhibited a gradual decrease in gene expression levels over AA-2G concentration. In the PPI network of m6A-related DEGs in profile 7, the cluster of metallopeptidase inhibitor 1 (Timp1), intercellular adhesion molecule 1 (Icam1), insulin-like growth factor 1 (Igf1), matrix metallopeptidase 2 (Mmp2), serpin family E member 1 (Serpine1), C-X-C motif chemokine ligand 2 (Cxcl2), galectin 3 (Lgals3) and angiopoietin-1 (Angpt1) was the top hub gene cluster. The expression of all hub genes was significantly increased after AA-2G intervention (P < 0.05), and the expression of Igf1 and Timp1 increased with increasing intervention concentration. The m6A epigenetic modifications were involved in the AA-2G-induced formation of BMSCs. Igf1, Serpine1 and Cxcl2 in DEGs were enriched for tissue repair, promotion of endothelial and epithelial proliferation and regulation of apoptosis.

Cerium Vanadate Nanozyme with pH-Dependent Dual Enzymatic Activity for Glioblastoma Targeted Therapy and Postradiotherapy Damage Protection.

Nanocatalytic therapy is an emerging technology that uses synthetic nanoscale enzyme mimics for biomedical treatment. However, in the field of neuroscience, achieving neurological protection while simultaneously killing tumor cells is a technical challenge. Herein, we synthesized a biomimic and translational cerium vanadate (CeVO4) nanozyme for glioblastoma (GBM) therapy and the repair of brain damage after GBM ionizing radiation (IR). This system exhibited pH dependence: it showed potent Superoxide dismutase (SOD) enzyme activity in a neutral environment and Peroxidase (POD) enzyme activity in an acidic environment. In GBM cells, this system acted in lysosomes, causing cellular damage and reactive oxygen species (ROS) accumulation; in neuronal cells, this nanozyme could undergo lysosomal escape and nanozyme aggregation with mitochondria, reversing the mitochondrial damage caused by IR and restoring the expression level of the antiapoptotic BCL-2 protein. Mechanistically, we believe that this distribution difference is related to the specific uptake internalization mechanism and lysosomal repair pathway in neurons, and ultimately led to the dual effect of tumor killing and nerve repair in the in vivo model. In summary, this study provides insight into the repair of brain damage after GBM radiation therapy.

Detection and identification of Bogia coconut syndrome phytoplasma from seed-associated tissues and seedlings of coconut (Cocos nucifera) and betel nut (Areca catechu).

Evidence for seed transmission of phytoplasmas has grown in several pathosystems including coconut (Cocos nucifera). Bogia coconut syndrome (BCS) is a disease associated with the lethal yellowing syndrome associated with the presence of 'Candidatus Phytoplasma noviguineense' that affects coconut, betel nut (Areca catechu) and bananas (Musa spp.) in Papua New Guinea. Coconut and betel nut drupes were sampled from BCS-infected areas in Papua New Guinea, dissected, the extracted nucleic acid was used in polymerase chain reaction (PCR), and loop mediated isothermal amplification (LAMP) used to check for presence of phytoplasma DNA. In a second study, drupes of both plant species were collected from multiple field sites and grown in insect-proof cages. Leaf samples taken at 6 months were also tested with PCR and LAMP. The studies of dissected coconut drupes detected phytoplasma DNA in several tissues including the embryo. Drupes from betel nut tested negative. Among the seedlings, evidence of possible seed transmission was found in both plant species. The results demonstrate the presence of 'Ca. P. noviguineense' in coconut drupes and seedlings, and in seedlings of betel nut; factors that need to be considered in ongoing management and containment efforts.

The mechanism of epigallocatechin-3-gallate inhibiting the antigenicity of ß-lactoglobulin under pH 6.2, 7.4 and 8.2: Multi-spectroscopy and molecular simulation methods.

The antigenicity of ß-lactoglobulin (ß-LG) can be influenced by pH values and reduced by epigallocatechin-3-gallate (EGCG). However, a detailed mechanism concerning EGCG decreasing the antigenicity of ß-LG at different pH levels lacks clarity. Here, we explore the inhibition mechanism of EGCG on the antigenicity of ß-LG at pH 6.2, 7.4 and 8.2 using enzyme-linked immunosorbent assay, multi-spectroscopy, mass spectrometry and molecular simulations. The results of Fourier transform infrared spectroscopy (FTIR) and circular dichroism (CD) elucidate that the noncovalent binding of EGCG with ß-LG induces variations in the secondary structure and conformations of ß-LG. Moreover, EGCG inhibits the antigenicity of ß-LG the most at pH 7.4 (98.30 %), followed by pH 6.2 (73.18 %) and pH 8.2 (36.24 %). The inhibitory difference is attributed to the disparity in the number of epitopes involved in the interacting regions of EGCG and ß-LG. Our findings suggest that manipulating pH conditions may enhance the effectiveness of antigenic inhibitors, with the potential for further application in the food industry.

Acupoint stimulation for long COVID: A promising intervention:.

"Long COVID" is a sustained symptom following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). According to recent statistics, at least 65 million people have long COVID, which poses a long-term threat to human health. The pathogenic mechanisms of coronavirus disease 2019 (COVID-19) are complex and affect multiple organs and systems. Common symptoms include palpitations, breathing difficulties, attention and memory deficits, fatigue, anxiety, and depression. It is difficult to achieve satisfactory treatment effect with a single intervention. Currently, treatment strategies for long COVID are still in the exploratory stage, and there is an urgent need to find appropriate and effective methods for long COVID treatment. Traditional Chinese medicine is effective in treating the various phases of COVID-19. Previous studies have shown that acupoint stimulation therapy is effective in improving palpitations, dyspnea, cognitive impairment, anxiety, depression, and other symptoms in patients. According to previous studies, acupoint stimulation may improve various symptoms related to long COVID. This paper discusses the potential application value of acupoint stimulation in the treatment of long COVID-related symptoms, based on the common sequelae of various systems involved in long COVID, and the effect of acupoint stimulation in the treatment of similar symptoms and diseases in recent years.

Opportunities and challenges related to ferroptosis in glioma and neuroblastoma.

A newly identified form of cell death known as ferroptosis is characterized by the peroxidation of lipids in response to iron. Rapid progress in research on ferroptosis in glioma and neuroblastoma has promoted the exploitation of ferroptosis in related therapy. This manuscript provides a review of the findings on ferroptosis-related therapy in glioblastoma and neuroblastoma and outlines the mechanisms involved in ferroptosis in glioma and neuroblastoma. We summarize some recent data on traditional drugs, natural compounds and nanomedicines used as ferroptosis inducers in glioma and neuroblastoma, as well as some bioinformatic analyses of genes involved in ferroptosis. Moreover, we summarize some data on the associations of ferroptosis with the tumor immunotherapy and TMZ drug resistance. Finally, we discuss future directions for ferroptosis research in glioma and neuroblastoma and currently unresolved issues.

Experimental Study on Hot Spot Stresses of Curved Composite Twin-Girder Bridges.

Curved composite twin-girder bridges are suitable for mountainous areas, due to their advantages of light self-weight, excellent mechanical performance, and fewer construction requirements. It has been found that many composite twin-girder bridges collapsed due to fatigue failure. However, the literature review showed no relevant studies on the fatigue performance of curved composite twin-girder bridges. Because of this, the specimen of 1:2 scale curved composite twin-girder bridge in accordance with the design scheme of Xizhen Bridge in China was designed and tested. Three possible fatigue details were selected: cruciform connections, transverse attachments, and transverse splices named Class I, Class II, and Class III. For the test data of nominal stress (NS), equations were proposed to convert the strain value into the internal force of the fatigue detail position. The stress caused by torsion accounts for 2.8% of the total stress, which is almost negligible. The fatigue evaluation process based on the hot spot stress (HSS) S-N curve method is presented. The HSS method is more conservative than the NS S-N curve method in predicting the fatigue life of complex structures with high-stress concentrations.

Pancancer landscape analysis of the thymosin family identified TMSB10 as a potential prognostic biomarker and immunotherapy target in glioma.

BACKGROUND: Thymosin family genes (TMSs), biologically important peptides with diverse intracellular and extracellular functions, have been shown to promote the progression of multiple cancers. However, multiomics characterization of TMSs and their role in human cancer prognosis has not been systematically performed. METHODS: We performed a comprehensive analysis of TMSs and thymosin ß10 (TMSB10) using multiomics data from more than 10,000 tumor samples of 33 cancer types from The Cancer Genome Atlas (TCGA). We used single-sample gene set enrichment analysis (ssGSEA) and the gene set variation analysis (GSVA) algorithm to investigate the differences in tumor microenvironment (TME) cell infiltration and functional annotation for individual tumor samples, respectively. The role of TMSB10 in the malignant progression of glioma, the promotion of macrophage infiltration,and immunosuppressive polarization, and the combination drug efficacy were assessed via biological function assays. RESULTS: We comprehensively assessed genomic mutations, expression dysregulation, prognosis and immunotherapeutic response across 33 human cancer samples and showed that TMSB10 is specifically overexpressed in almost all types of cancer tissues. Further pan-cancer analysis showed that TMSB10 is closely related to the biological function, immune regulation and prognosis of glioma. Similar results were also found in several public glioma cohorts and our Qilu local cohort. Further integration with other biological experiments revealed the key roles of TMSB10 in the malignant progression of glioma, the promotion of macrophage infiltration and immunosuppressive polarization. We also identified multiple drugs targeting cells with high TMSB10 expression and validated that knockdown of TMSB10 improved the efficacy of selumetinib (a MEK1/2 inhibitor approved by the FDA for the treatment of neurofibromatosis-associated tumors) and anti-PD1 treatment in glioma. CONCLUSION: These results indicate that TMSB10 holds promise as a novel prognostic marker and therapeutic target, providing a theoretical basis for the development of more effective and targeted clinical treatment strategies for glioma patients.

Preparation and evaluation of a silk fibroin-polycaprolactone biodegradable biomimetic tracheal scaffold.

In tracheal tissue engineering, the construction of tracheal scaffolds with adequate biodegradable mechanical capacity and biological functions that mimic the structure of a natural trachea is challenging. To explore the feasibility of preparing biomimetic degradable scaffolds with C-type cartilage rings and an inner tracheal wall of polycaprolactone and silk fibroin. A mold was made according to the diameter of a rabbit trachea, and a silk fibroin tube and polycaprolactone ring attached to the tube were obtained by solution casting. The ring was fixed to the tube at a specific spacing using electrostatic spinning technology to construct a biomimetic tracheal scaffold; its porous structure was observed by scanning electron microscopy, its degradation properties were determined by in vitro enzymatic hydrolysis and its mechanical properties were obtained by pressure testing. The composite scaffold was transplanted subcutaneously into a rabbit model, and the scaffold was taken at 1, 2, and 4 weeks after surgery for sectioning to observe pre-vascularization. The Medical Ethics Committee of Guangdong Provincial People's Hospital approved the study. The general view of the biomimetic scaffold: the polycaprolactone ring was fixed firmly on the outer wall of the silk fibroin tube; the two corresponded in size, and they fitted closely. The surface of the polycaprolactone ring was smooth and dense, while the surface of the silk fibroin tube could be seen as a uniform porous structure. Scanning electron microscopy showed that the surface and profile of the fibroin tube had a uniform pore size and distribution. The pores were connected to form a network. In vitro, enzymatic hydrolysis experiments confirmed that the fibroin was degraded easily, with most being degraded at the end of week 1. The degradation slowed at 2, 3, and 4 weeks, while the degradation of polycaprolactone was extremely slow. A compression test showed that the compressive resistance of the silk fibroin-polycaprolactone biomimetic scaffolds was much better than that of the rabbit trachea at close thickness. In the tissue staining experiments, as the material degraded, fibrous tissues and blood vessels grew to replace the material, allowing the scaffold to obtain a blood supply and better mechanical properties. A quantitative analysis of CD31 showed that the results for the vascularization of the scaffold were better at 4 weeks than at 2 weeks following subcutaneous grafting (P < .05). The results confirmed that it is feasible to prepare porous, degradable silk fibroin-polycaprolactone biomimetic scaffolds with good mechanical properties and epithelial biological functions by mold casting.

Photoluminescence mechanism of carbon dots: triggering high-color-purity red fluorescence emission through edge amino protonation.

Due to complex structure and surface functionalities, photoluminescence mechanisms of Carbon Dots are unknown, and it is challenging to synthesize Carbon Dots to achieve the desired optical properties. Herein, Carbon Dots simultaneously exhibiting high-color-purity (FWHM~24 nm) long wavelength one-photon fluorescence emission at 620 nm and NIR induced two-photon fluorescence emission at 630 and 680 nm are prepared by edge amino protonation treatment. Systematic analysis reveals that the protonation of 2,3-diaminophenazine changes the molecular state of Carbon Dots, decreases the photon transition band gap, and triggers red fluorescence emission with the dramatically narrowed peak width. As the oxidation products of reactant o-phenylendiamine, the emergence of 2,3-diaminophenazine as a photoluminescence determiner suggests that fluorophore products of precursor conversion are viable determinants of the desired luminescence properties of Carbon Dots. This work shows a new way for predicting and controlling photoluminescence properties of Carbon Dots, and may guide the development of tunable Carbon Dots for a broad range of applications.

The high-risk factors of different severities of bronchopulmonary dysplasia (BPD) based on the national institute of child health and human development (NICHD) diagnosis criteria in 2018.

OBJECTIVE: To investigate the clinical characteristics of preterm infants with different severities of bronchopulmonary dysplasia (BPD) and disclose the high-risk factors of exacerbating BPD. METHODS: Collection of clinical data of 91 preterm infants admitted to the NICU and diagnosed with BPD, categorized in groups according to the disease severity: 41 mild cases,, 24 moderate cases, and 26 severe cases. Comparison and analysis of perinatal risk factors, treatment, complications and prognosis of the infants with different severity degrees. RESULTS: The severe group had a higher proportion of infants with congenital heart disease (CHD) higher than the moderate group (P < 0.05), and a higher ratio of pneumonia and mechanical ventilation (MV) ≥ seven days than the mild group (P < 0.05). The severe group also presented higher reintubation incidence than both the mild and moderate groups (P < 0.05). The groups presented different (P < 0.05) incidence rates of hemodynamically significant patent ductus arteriosus (hsPDA) . Ridit analysis suggested that the premature infants (PIs) with hsPDA, multiple microbial pulmonary infections, or Klebsiella pneumoniae pneumonia had more severe illness. CONCLUSION: CHD, hsPDA, MV ≥ seven days, reintubation, pneumonia, especially multiple microbial pulmonary infections, and Klebsiella pneumoniae pneumonia are correlated with the severity of BPD and can be used as BPD progression predictor.

Mendelian randomization analysis identified genes potentially pleiotropically associated with periodontitis.

OBJECTIVE: To prioritize genes that were pleiotropically or potentially causally associated with periodontitis. METHODS: We applied the summary data-based Mendelian randomization (SMR) method integrating genome-wide association study (GWAS) for periodontitis and expression quantitative trait loci (eQTL) data to identify genes that were pleiotropically associated with periodontitis. We performed separate SMR analysis using CAGE eQTL data and GTEx eQTL data. SMR analysis were done for participants of European and East Asian ancestries, separately. RESULTS: We identified multiple genes showing pleiotropic association with periodontitis in participants of European ancestry and participants of East Asian ancestry. PDCD2 (corresponding probe: ILMN_1758915) was the top hit showing pleotropic association with periodontitis in the participants of European ancestry using CAGE eQTL data, and BX093763 (corresponding probe: ILMN_1899903) and AC104135.3 (corresponding probe: ENSG00000204792.2) were the top hits in the participants of East Asian ancestry using CAGE eQTL data and GTEx eQTL data, respectively. CONCLUSION: We identified multiple genes that may be involved in the pathogenesis of periodontitis in participants of European ancestry and participants of East Asian ancestry. Our findings provided important leads to a better understanding of the mechanisms underlying periodontitis and revealed potential therapeutic targets for the effective treatment of periodontitis.

The significance of an integrated management mode of prenatal diagnosis-postnatal treatment for critical congenital heart disease in newborns.

BACKGROUND: Congenital heart disease (CHD) is the most common congenital defect in human beings. The purpose of this article is to investigate impact of an integrated management mode of 'prenatal diagnosis-postnatal treatment' on birth, surgery, prognosis and complications associated with critical CHD (CCHD) in newborns. METHODS: A retrospective analysis of the medical records of newborns diagnosed with CCHD were divided into two groups: prenatal diagnosis and postnatal diagnosis. The demographics, clinical characteristics, surgical status, prognosis and complications of the two groups were compared and the differences identified. RESULTS: Among the 290 newborns with CCHD, 97 (33.4%) were prenatally diagnosed and 193 (66.6%) were postnatally diagnosed. Newborns in the prenatal diagnostic group were hospitalized immediately after birth, whereas the median age of admission was 6.00 (3.00-12.00) days in postnatal diagnostic group, P=0.000. In terms of postnatal symptoms and signs, the incidence of anhelation, cyanosis and cardiac murmur was higher in the postnatal diagnostic group. The rates of preoperative intubation, postoperative open chest exploration and treatment abandonment were higher in the postnatal diagnostic group. The postnatal diagnostic group was more prone to postoperative complications, such as pneumonia and hypoxic-ischemic brain damage. The preoperative mortality [0 (0.0%) vs. 12 (6.2%), P=0.028] in the prenatal diagnostic group was lower than that in the postnatal diagnostic group. And the one-year survival rate of the prenatal diagnostic group was higher (log-rank test P=0.034). CONCLUSIONS: The integrated management mode of prenatal diagnosis-postnatal treatment can improve postnatal symptoms, reduces complications, reduces preoperative mortality and increases one-year survival rates in newborns with CCHD.

Mendelian randomization integrating GWAS and eQTL data revealed genes pleiotropically associated with major depressive disorder.

Previous genome-wide association studies (GWAS) have identified potential genetic variants associated with the risk of major depressive disorder (MDD), but the underlying biological interpretation remains largely unknown. We aimed to prioritize genes that were pleiotropically or potentially causally associated with MDD. We applied the summary data-based Mendelian randomization (SMR) method integrating GWAS and gene expression quantitative trait loci (eQTL) data in 13 brain regions to identify genes that were pleiotropically associated with MDD. In addition, we repeated the analysis by using the meta-analyzed version of the eQTL summary data in the brain (brain-eMeta). We identified multiple significant genes across different brain regions that may be involved in the pathogenesis of MDD. The prime-specific gene BTN3A2 (corresponding probe: ENSG00000186470.9) was the top hit showing pleiotropic association with MDD in 9 of the 13 brain regions and in brain-eMeta, after correction for multiple testing. Many of the identified genes are located in the human major histocompatibility complex (MHC) region on chromosome 6 and are mainly involved in the immune response. Our SMR analysis indicated that multiple genes showed pleiotropic association with MDD across the brain regions. These findings provided important leads to a better understanding of the mechanism of MDD and revealed potential therapeutic targets for the prevention and effective treatment of MDD.

The Application of a Bone Marrow Mesenchymal Stem Cell Membrane in the Vascularization of a Decellularized Tracheal Scaffold.

Airway stenosis is a common problem in the neonatal intensive care unit (NICU) and pediatric intensive care unit (PICU). A tissue-engineered trachea is a new therapeutic method and a research hotspot. Successful vascularization is the key to the application of a tissue-engineered trachea. However, successful vascularization studies lack a complete description. In this study, it was assumed that rabbit bone marrow mesenchymal stem cells were obtained and induced by ascorbic acid to detect the tissue structure, ultrastructure, and gene expression of the extracellular matrix. A vascular endothelial cell culture medium was added in vitro to induce the vascularization of the stem cell sheet (SCS), and the immunohistochemistry and gene expression of vascular endothelial cell markers were detected. At the same time, vascular growth-related factors were added and detected during SCS construction. After the SCS and decellularized tracheal (DT) were constructed, a tetrandrine allograft was performed to observe its vascularization potential. We established the architecture and identified rabbit bone marrow mesenchymal stem cell membranes by 14 days of ascorbic acid, studied the role of a vascularized membrane in inducing bone marrow mesenchymal stem cells by in vitro ascorbic acid, and assessed the role of combining the stem cell membranes and noncellular tracheal scaffolds in vivo. Fourteen experiments confirmed that cell membranes promote angiogenesis at gene level. The results of 21-day in vitro experiments showed that the composite tissue-engineered trachea had strong angiogenesis. In vivo experiments show that a composite tissue-engineered trachea has strong potential for angiogenesis. It promotes the understanding of diseases of airway stenosis and tissue-engineered tracheal regeneration in newborns and small infants.

Mendelian randomization analysis identified genes pleiotropically associated with the risk and prognosis of COVID-19.

OBJECTIVES: COVID-19 has caused a large global pandemic. Patients with COVID-19 exhibited considerable variation in disease behavior. Pervious genome-wide association studies have identified potential genetic variants involved in the risk and prognosis of COVID-19, but the underlying biological interpretation remains largely unclear. METHODS: We applied the summary data-based Mendelian randomization (SMR) method to identify genes that were pleiotropically associated with the risk and various outcomes of COVID-19, including severe respiratory confirmed COVID-19 and hospitalized COVID-19. RESULTS: In blood, we identified 2 probes, ILMN_1765146 and ILMN_1791057 tagging IFNAR2, that showed pleiotropic association with hospitalized COVID-19 (ß [SE]=0.42 [0.09], P = 4.75 × 10-06 and ß [SE]=-0.48 [0.11], P = 6.76 × 10-06, respectively). Although no other probes were significant after correction for multiple testing in both blood and lung, multiple genes as tagged by the top 5 probes were involved in inflammation or antiviral immunity, and several other tagged genes, such as PON2 and HPS5, were involved in blood coagulation. CONCLUSIONS: We identified IFNAR2 and other potential genes that could be involved in the susceptibility or prognosis of COVID-19. These findings provide important leads to a better understanding of the mechanisms of cytokine storm and venous thromboembolism in COVID-19 and potential therapeutic targets for the effective treatment of COVID-19.

The high-risk factors of different severities of bronchopulmonary dysplasia (BPD) based on the national institute of child health and human development (NICHD) diagnosis criteria in 2018 / Os fatores de alto risco de diferentes gravidades de displasia broncopulmonar (DBP) com base no instituto nacional de saúde infantil e desenvolvimento humano (NICHD): critérios de diagnóstico em 2018

ABSTRACT Objective To investigate the clinical characteristics of preterm infants with different severities of bronchopulmonary dysplasia (BPD) and disclose the high-risk factors of exacerbating BPD. Methods Collection of clinical data of 91 preterm infants admitted to the NICU and diagnosed with BPD, categorized in groups according to the disease severity: 41 mild cases,, 24 moderate cases, and 26 severe cases. Comparison and analysis of perinatal risk factors, treatment, complications and prognosis of the infants with different severity degrees. Results The severe group had a higher proportion of infants with congenital heart disease (CHD) higher than the moderate group (P < 0.05), and a higher ratio of pneumonia and mechanical ventilation (MV) ≥ seven days than the mild group (P < 0.05). The severe group also presented higher reintubation incidence than both the mild and moderate groups (P < 0.05). The groups presented different (P < 0.05) incidence rates of hemodynamically significant patent ductus arteriosus (hsPDA) . Ridit analysis suggested that the premature infants (PIs) with hsPDA, multiple microbial pulmonary infections, or Klebsiella pneumoniae pneumonia had more severe illness. Conclusion CHD, hsPDA, MV ≥ seven days, reintubation, pneumonia, especially multiple microbial pulmonary infections, and Klebsiella pneumoniae pneumonia are correlated with the severity of BPD and can be used as BPD progression predictor.

RESUMO Objetivo Investigar as características clínicas de prematuros com diferentes gravidades de displasia broncopulmonar (DBP) e divulgar os fatores de alto risco para a DBP. Métodos Coleta de dados clínicos de 91 prematuros internados em UTIN com diagnóstico de DBP, categorizados em grupos de acordo com a gravidade da doença: 41 casos leves, 24 casos moderados e 26 casos graves. Foram feitas a comparação e a análise de fatores de risco perinatais, tratamento, complicações e prognóstico de lactentes com diferentes graus de gravidade. Resultados O grupo grave teve uma proporção maior de bebês com doença cardíaca congênita (DCC) do que o grupo moderado (p < 0,05) e com pneumonia e ventilação mecânica (VM) ≥ 7 dias do que o grupo leve (p < 0,05). O grupo grave também apresentou maior incidência de reintubação do que os grupos leve e moderado (p < 0,05). Os grupos apresentaram diferentes (p < 0,05) taxas de incidência de persistência do canal arterial hemodinamicamente significativa (PCAhs). A análise de ridit sugeriu que os bebês prematuros (BPs) com PCAhs, infecções pulmonares microbianas múltiplas ou pneumonia por Klebsiella pneumoniae tinham doenças mais graves. Conclusão DCC, PCAhs, VM ≥ 7 dias, reintubação, pneumonia, principalmente infecções pulmonares microbianas múltiplas, e pneumonia por Klebsiella pneumoniae estão correlacionadas com a gravidade da DBP e podem ser usadas como preditoras de progressão da DBP.

Mendelian randomization analysis identified genes pleiotropically associated with the risk and prognosis of COVID-19.

OBJECTIVES: COVID-19 has caused a large global pandemic. Patients with COVID-19 exhibited considerable variation in disease behavior. Pervious genome-wide association studies have identified potential genetic variants involved in the risk and prognosis of COVID-19, but the underlying biological interpretation remains largely unclear. METHODS: We applied the summary data-based Mendelian randomization (SMR) method to identify genes that were pleiotropically associated with the risk and various outcomes of COVID-19, including severe respiratory confirmed COVID-19 and hospitalized COVID-19. RESULTS: In blood, we identified 2 probes, ILMN_1765146 and ILMN_1791057 tagging IFNAR2, that showed pleiotropic association with hospitalized COVID-19 (Beta; [SE]=0.42 [0.09], P=4.75E-06 and Beta; [SE]=-0.48 [0.11], P=6.76E-06, respectively). Although no other probes were significant after correction for multiple testing in both blood and lung, multiple genes as tagged by the top 5 probes were involved in inflammation or antiviral immunity, and several other tagged genes, such as PON2 and HPS5, were involved in blood coagulation. CONCLUSIONS: We identified IFNAR2 and other potential genes that could be involved in the susceptibility or prognosis of COVID-19. These findings provide important leads to a better understanding of the mechanisms of cytokine storm and venous thromboembolism in COVID-19 and potential therapeutic targets for the effective treatment of COVID-19.

Endophytic effects of Aspergillus oryzae on radish (Raphanus sativus) and its herbivore, Plutella xylostella.

MAIN CONCLUSION: We provide evidence that Aspergillus oryzae not only acts as an endophyte in Raphanus sativus, but also works as a plant growth promoter and provides some protection against its herbivore, Plutella xylostella affecting its feeding rate, mortality and fitness parameters, thereby contributing to the pest population suppression. Seed inoculation of radish seeds with the fungus Aspergillus oryzae allowed its establishment as an endophyte promoting plant growth and negatively affecting fitness parameters of its major herbivore, diamondback moth, Plutella xylostella. Endophytic fungi may contribute to the growth of their host plants and enhance resistance to herbivores and diseases. We evaluated the effect of A. oryzae (Ahlburg) E. Cohn as an endophyte in radish (Raphanus sativus L.) on growth and development of the plants themselves and their major herbivore, the diamondback moth P. xylostella (L). A. oryzae colonization rates in leaves were significantly higher than in roots and stems, with a rate of 80% in leaves, 40% in stems and 20% in roots 1 week after seed inoculation. Colonization gradually decreased in the various plant tissues, and disappeared completely in roots, stems and leaves within 2, 5 and 7 weeks, respectively. A. oryzae did not affect seed germination; however, it promoted radish growth with endophytic plants attaining average heights of 116 mm compared to 99.6 mm in the controls at the third week post-inoculation. The P. xylostella fitness parameters, consumption, larval and pupal weights, and feeding on the endophytic plants were significantly lower than the controls, while larval mortality was significantly higher. Larvae fed on endophytic plants consumed 0.46 mg less leaf matter in the first week post seed inoculation and weighed 0.83 mg less as mature 4th instars than controls. We have demonstrated that A. oryzae can establish as an endophyte in R. sativus through seed inoculation providing some plant growth promotion and protection against its herbivore by increasing its mortality and negatively affecting its fitness parameters, suggesting that adopting seed treatments with A. oryzae may be beneficial in the commercial cultivation of radish.