DEAD-BOX RNA HELICASE 27 regulates microRNA biogenesis, zygote division, and stem cell homeostasis.

After double fertilization, zygotic embryogenesis initiates a new life cycle, and stem cell homeostasis in the shoot apical meristem (SAM) and root apical meristem (RAM) allows plants to produce new tissues and organs continuously. Here, we report that mutations in DEAD-BOX RNA HELICASE 27 (RH27) affect zygote division and stem cell homeostasis in Arabidopsis (Arabidopsis thaliana). The strong mutant allele rh27-1 caused a zygote-lethal phenotype, while the weak mutant allele rh27-2 led to minor defects in embryogenesis and severely compromised stem cell homeostasis in the SAM and RAM. RH27 is expressed in embryos from the zygote stage, and in both the SAM and RAM, and RH27 is a nucleus-localized protein. The expression levels of genes related to stem cell homeostasis were elevated in rh27-2 plants, alongside down-regulation of their regulatory microRNAs (miRNAs). Further analyses of rh27-2 plants revealed reduced levels of a large subset of miRNAs and their pri-miRNAs in shoot apices and root tips. In addition, biochemical studies showed that RH27 associates with pri-miRNAs and interacts with miRNA-biogenesis components, including DAWDLE, HYPONASTIC LEAVES 1, and SERRATE. Therefore, we propose that RH27 is a component of the microprocessor complex and is critical for zygote division and stem cell homeostasis.

Sodium oligomannate activates the enteroendocrine-vagal afferent pathways in APP/PS1 mice.

Enteroendocrine cells (EECs) and vagal afferent neurons constitute functional sensory units of the gut, which have been implicated in bottom-up modulation of brain functions. Sodium oligomannate (GV-971) has been shown to improve cognitive functions in murine models of Alzheimer's disease (AD) and recently approved for the treatment of AD patients in China. In this study, we explored whether activation of the EECs-vagal afferent pathways was involved in the therapeutic effects of GV-971. We found that an enteroendocrine cell line RIN-14B displayed spontaneous calcium oscillations due to TRPA1-mediated calcium entry; perfusion of GV-971 (50, 100 mg/L) concentration-dependently enhanced the calcium oscillations in EECs. In ex vivo murine jejunum preparation, intraluminal infusion of GV-971 (500 mg/L) significantly increased the spontaneous and distension-induced discharge rate of the vagal afferent nerves. In wild-type mice, administration of GV-971 (100 mg· kg-1 ·d-1, i.g. for 7 days) significantly elevated serum serotonin and CCK levels and increased jejunal afferent nerve activity. In 7-month-old APP/PS1 mice, administration of GV-971 for 12 weeks significantly increased jejunal afferent nerve activity and improved the cognitive deficits in behavioral tests. Sweet taste receptor inhibitor Lactisole (0.5 mM) and the TRPA1 channel blocker HC-030031 (10 µM) negated the effects of GV-971 on calcium oscillations in RIN-14B cells as well as on jejunal afferent nerve activity. In APP/PS1 mice, co-administration of Lactisole (30 mg ·kg-1 ·d-1, i.g. for 12 weeks) attenuated the effects of GV-971 on serum serotonin and CCK levels, vagal afferent firing, and cognitive behaviors. We conclude that GV-971 activates sweet taste receptors and TRPA1, either directly or indirectly, to enhance calcium entry in enteroendocrine cells, resulting in increased CCK and 5-HT release and consequent increase of vagal afferent activity. GV-971 might activate the EECs-vagal afferent pathways to modulate cognitive functions.

Nanoparticle-modified microrobots for in vivo antibiotic delivery to treat acute bacterial pneumonia.

Bioinspired microrobots capable of actively moving in biological fluids have attracted considerable attention for biomedical applications because of their unique dynamic features that are otherwise difficult to achieve by their static counterparts. Here we use click chemistry to attach antibiotic-loaded neutrophil membrane-coated polymeric nanoparticles to natural microalgae, thus creating hybrid microrobots for the active delivery of antibiotics in the lungs in vivo. The microrobots show fast speed (>110 µm s-1) in simulated lung fluid and uniform distribution into deep lung tissues, low clearance by alveolar macrophages and superb tissue retention time (>2 days) after intratracheal administration to test animals. In a mouse model of acute Pseudomonas aeruginosa pneumonia, the microrobots effectively reduce bacterial burden and substantially lessen animal mortality, with negligible toxicity. Overall, these findings highlight the attractive functions of algae-nanoparticle hybrid microrobots for the active in vivo delivery of therapeutics to the lungs in intensive care unit settings.

Super-enhancer-associated SNHG15 cooperating with FOSL1 contributes to bladder cancer progression through the WNT pathway.

Small nucleolar RNA host gene 15 (SNHG15) plays an oncogenic role in many cancers. However, the role of SNHG15 in bladder cancer (BLCA) remains unclear. In this study, the regulation of SNHG15 on the activities of BLCA cells (T24 and RT112) was investigated. In detail, super-enhancers (SEs), differentially expressed genes, and functional enrichment were detected by bioinformatic analyses. Mutant cell lines lacking SNHG15-SEs were established using CRISPR-Cas9. Relative gene expression was detected by quantitative polymerase chain reaction (qPCR), western blot, in situ hybridization, and immunohistochemistry assays. Cell senescence, apoptosis, viability, and proliferation were measured. Chromatin immunoprecipitation (ChIP)-qPCR and luciferase reporter gene assays were conducted to analyze the interactions between genes. A novel super-enhancer of SNHG15 (SNHG15-SEs) was discovered in several BLCA datasets. The deletion of SNHG15-SEs resulted in a significant downregulation of SNHG15. Mechanistically, the core active region of SNHG15-SEs recruited the transcription factor FOSL1 to facilitate the SNHG15 transcription, thereby inducing the proliferation and metastasis of BLCA cells. Deletion of SNHG15-SEs inhibited the growth and metastasis of T24 and RT112 cells by inactivating the WNT/CTNNB1 pathway activation. Overexpression of FOSL1 in SNHG15-SEs restored the cell proliferation and metastasis. Next, a xenograft mouse model showed that SNHG15-SEs deletion inhibited the proliferation and metastasis of BLCA cells in vivo. Collectively, our data indicate that SNHG15-SEs recruit FOSL1 to promote the expression of SNHG15 which interacts with CTNNB1 in the nucleus to activate the transcription of ADAM12, leading to the malignance of BLCA cells.

Integrated analysis of a miRNA-mRNA network related to immunity and autophagy in Macrobrachium rosenbergii infected with Aeromonas hydrophila.

MicroRNAs (miRNAs) are a group of RNAs that regulate gene expression in the post-transcriptionally. miRNAs can regulate numerous processes, such as the immune response, due to their dynamic expression patterns. The giant freshwater prawn Macrobrachium rosenbergii is a major freshwater aquaculture prawn that is attacked by various bacteria, including Aeromonas hydrophila. For this study, we performed an analysis of the miRNA and mRNA transcriptome analysis of M. rosenbergii which was infected with A. hydrophila. We identified 56 differentially expressed miRNAs (DEMs) and 1542 differentially expressed mRNAs. Furthermore, an integrated analysis of miRNA-mRNA expression led to the identification of 729 differentially predicted target genes (DETGs) of the DEMs. Multiple functional categories related to immunity, apoptosis, and autophagy were found to be enriched in the DETGs. During the infection of M. rosenbergii by A. hydrophila, an elaborate regulatory network involving Toll and immune deficiency (IMD) signaling, mitogen-activated protein kinase (MAPK) signaling, lysosome, and cell apoptosis was formed by a complex interplay of 40 crucial DEMs and 22 DETGs, all associated with the immune and autophagy pathway. The findings suggest that infection with A. hydrophila triggers intricate responses in both miRNA and mRNA, significantly impacting immune and autophagy processes in M. rosenbergii.

Molecular identification and functional exploration of interleukin-20 in snakehead (Channa argus) involved in bacterial invasion and the proliferation of head kidney leukocytes.

As an inflammatory cytokine of the interleukin-20 (IL-20) subfamily, IL-20 has various functions in immune defenses, inflammatory diseases, tissue regeneration, cancer, and metabolism. Although the characteristics and functions of mammalian IL-20 have been clarified, those of fish IL-20 remain unclear. In this study, the IL-20 gene from the snakehead Channa argus (shIL-20) was cloned and functionally characterized. Similar to the IL-20 homologues of other species, the shIL-20 has a five exon/four intron structure in the coding region. The open reading frame of shIL-20 consists of 528 base pairs and encodes 175 amino acids (aa), including a signal peptide (aa 1-24) and a mature peptide (aa 25-175). The mature shIL-20 protein has six conserved cysteine residues, which occur in the IL-20 proteins of all species analyzed, and an additional cysteine residue (Cys-82) found only in the IL-20 proteins of several teleosts. The modeled tertiary structure of shIL-20 is similar with that of Homo sapiens IL-20. The shIL-20 was expressed constitutively in all the tissues analyzed, and its transcription was induced in the spleen and head kidney by Aeromonas schubertii and Nocardia seriolae in vivo and in head kidney leukocytes (HKLs) by lipoteichoic acid, lipopolysaccharide, and polyinosinic-polycytidylic acid in vitro. The recombinant shIL-20 protein induced the transcription of tumor necrosis factor α1 (TNF-α1), TNF-α2, IL-1ß, and endogenous shIL-20, and promoted the proliferation of HKLs. In conclusion, these findings demonstrate that shIL-20 participates in the immune response to bacterial invasion and promotes leukocyte proliferation, offering new insights into the functions of fish IL-20 during pathogen invasion.

Extraction and Quantification of Nanoparticulate Mercury in Natural Soils.

Nanoparticulate mercury (Hg-NPs) are ubiquitous in nature. However, the lack of data on their concentration in soils impedes reliable risk assessments. This is due to the analytical difficulties resulting from low ambient Hg concentrations and background interferences of heterogeneous soil components. Here, coupled to single particle inductively coupled plasma-mass spectrometry (spICP-MS), a standardized protocol was developed for extraction and quantification of Hg-NPs in natural soils with a wide range of properties. High particle number-, particle mass-, and total mass-based recoveries were obtained for spiked HgS-NPs (74-120%). Indigenous Hg-NPs across soils were within 107-1011 NPs g-1, corresponding to 3-40% of total Hg on a mass basis. Metacinnabar was the primary Hg species in extracted samples from the Wanshan mercury mining site, as characterized by X-ray absorption spectroscopy and transmission electron microscopy. In agreement with the spICP-MS analysis, electron microscopy revealed comparable size distribution for nanoparticles larger than 27 nm. These indigenous Hg-NPs contributed to 5-65% of the measured methylmercury in soils. This work paves the way for experimental determinations of indigenous Hg-NPs in natural soils, which is critical to understand the biogeochemical cycling of mercury and thereby the methylation processes governing the public exposure to methylmercury.

The clinical differences between cough variant asthma cells and humoral immunology indicators.

The Purpose of this study was to study and analyze the clinical differences between cough variant asthma (CVA) cells and humoral immunology indicators. For this aim, 73 sick children with CVA were enrolled in this study and were admitted to the Pediatric Inpatient Department of Weifang Maternal and Child Health Hospital for treatment from April 2019 to May 2021. They were divided into the attack stage group (n=45) and the remission stage group (n=28). Meanwhile, 30 children with normal physical examination results were selected as normal controls. Differences in serum levels of TNF-, hs-CRP, IL-4, IL-5, IL-6 and IL-13 were compared among the three groups, as well as the differences in humoral immunology indicators such as T lymphocyte subsets CD3+, CD4+, CD8+, CD4+/ CD8+ and IgA, IgG, IgG, IgM, IgE, IgE and IgG subtypes. Results showed that serum levels of TNF-α and hs-CRP were significantly higher in the attack stage group than those in the remission stage group and normal control group, and the difference was statistically significant (P<0.05). The serum levels of TNF-α and hs-CRP were higher in the remission stage group than those in the normal control group, and the difference was not statistically significant (P>0.05). Serum levels of IL-4, IL-5, IL-6 and IL-13 were significantly higher in the attack stage group than those in the remission stage group and normal control group, and the difference was statistically significant (P<0.05). CD4+ and CD4+/CD8+ were significantly higher in the attack stage group than those in the remission stage group and normal control group, and the difference was statistically significant (P<0.05). The difference in serum levels of IgG1, IgG2 and IgG3 was not statistically significant (P>0.05) among the three groups. While the level of IgG4 subsets in the attack stage group was significantly higher than that in the remission stage group and normal control group, and the difference was statistically significant (P<0.05). Then the cytokines, cells and humoral immunology indicators of CVA patients are not in their normal range. They are involved in the pathogenesis of CVA. The combined detection is of great clinical significance in the diagnosis of early CVA to avoid misdiagnosis and missed diagnosis.

Comparison of Her-2/Neu Gene Amplification or Expression between IHC and FISH in BC.

This study aimed to analyze and compare the application of FISH and IHC in BC tissue Her-2 / neu gene amplification or expression. For this purpose, 110 patients with BC were selected. FISH and IHC were performed on the BC tissues that were surgically removed, and the results were compared and analyzed. The results showed that in 110 BC tissues, the expression of HER-2 protein was (+++) 25 cases (22.73%); (++) 44 cases (40%); (+) 26 cases (23.64%); (1) 15 cases (13.64%). There were 42 cases of HER-2 gene amplification in 110 BC tissues, and 68 cases had no amplification. IHC test positive (+++) is consistent with FISH positive coincidence rate, IHC test negative (+/-) is consistent with FISH negative coincidence rate, IHC test suspicious positive (++) compared with the FISH result, the difference is statistically significant. However, the total coincidence rate between IHC test results and FISH test results was 89.29 (25/28), and the two test methods were positively correlated. Generally, IHC positive and negative expressions are in good agreement with FISH test results. The suspected positive expression of IHC is inconsistent with the FISH test result, suggesting that the IHC test is suspicious, and the positive specimens need to be tested by FISH.

Nanomaterial Biointerfacing via Mitochondrial Membrane Coating for Targeted Detoxification and Molecular Detection.

Natural cell membranes derived from various cell sources have been successfully utilized to coat nanomaterials for functionalization. However, intracellular membranes from the organelles of eukaryotes remain unexplored. Herein, we choose mitochondrion as a representative cell organelle and coat outer mitochondrial membrane (OMM) from mouse livers onto nanoparticles and field-effect transistors (FETs) through a membrane vesicle-substrate fusion process. Polymeric nanoparticles coated with OMM (OMM-NPs) can bind with ABT-263, a B-cell lymphoma protein 2 (Bcl-2) inhibitor that targets the OMM. As a result, OMM-NPs effectively protect the cells from ABT-263 induced cell death and apoptosis in vitro and attenuated ABT-263-induced thrombocytopenia in vivo. Meanwhile, FET sensors coated with OMM (OMM-FETs) can detect and distinguish anti-Bcl-2 antibody and small molecule agonists. Overall, these results show that OMM can be coated onto the surfaces of both nanoparticles and functional devices, suggesting that intracellular membranes can be used as coating materials for novel biointerfacing.

Heavy metal pollution and net greenhouse gas emissions in a rice-wheat rotation system as influenced by partial organic substitution.

Substituting nitrogen fertilizer with organic manure is a common fertilization practice in farmland, but its potential effect on heavy metal pollution and greenhouse gas (GHG) emissions remains unclear. A three-year field experiment was conducted in the rice-wheat rotation system, with two different substitution ratios (25% and 50%) of sewage sludge compost (SS) and pig manure compost (PM). With the substitutions of SS and PM, the heavy metals, including Cu, Zn, Cd, and Pb were accumulated in the soil, but the pollution load index was <1 (0.39-0.66), indicating that soil was not polluted. Heavy metals Ni and Cu were mainly found in rice chaff, while Zn and Cd were accumulated in rice stalk, and the accumulation of Pb occurred in the leaf. For wheat, Ni, Cu, and Pb were accumulated in chaff, while grain and stalk had the highest concentrations of Zn and Cd, respectively. Moreover, the bioconcentration factor of heavy metals was 0-0.787, and their contents were below the standard limits for foods for rice and wheat in China, implying that the grains were unpolluted. Given the 5-8 fold increase in the sequestration rate of soil organic carbon with SS and PM substitutions, the annual net GHG emissions were reduced by 115-166%. Most importantly, 50% SS substitution exhibited the lowest net GHG emissions and highest rice and wheat yields. Overall, the results suggested that 50% SS substitution would be a feasible fertilization strategy that not only is unlikely to pose a high risk of soil and grain pollution but also significantly mitigates net GHG emissions and maintains high yields.

Sodium salicylate enhances neural excitation via reducing GABAergic transmission in the dentate gyrus area of rat hippocampus in vivo.

Sodium salicylate, one of the non-steroidal anti-inflammatory drugs, is widely prescribed in the clinic, but a high dose of usage can cause hyperactivity in the central nervous system, including the hippocampus. At present, the neural mechanism underlying the induced hyperactivity is not fully understood, in particular, in the hippocampus under an in vivo condition. In this study, we found that systemic administration of sodium salicylate increased the field excitatory postsynaptic potential slope and the population spike amplitude in a dose-dependent manner in the hippocampal dentate gyrus area of rats with in vivo field potential extracellular recordings, which indicates that sodium salicylate enhances basal synaptic transmission and neural excitation. In the presence of picrotoxin, a GABA-A receptor antagonist, sodium salicylate failed to increase the initial slope of the field excitatory postsynaptic potential and the amplitude of the population spike in vivo. To further explore how sodium salicylate enhances the neural excitation, we made whole-cell patch-clamp recordings from hippocampal slices. We found that perfusion of the slice with sodium salicylate decreased electrically evoked GABA receptor-mediated currents, increased paired-pulse ratio, and lowered frequency and amplitude of miniature inhibitory postsynaptic currents. Together, these results demonstrate that sodium salicylate enhances the neural excitation through suppressing GABAergic synaptic transmission in presynaptic and postsynaptic mechanisms in the hippocampal dentate gyrus area. Our findings may help understand the side effects caused by sodium salicylate in the central nervous system.

A very preterm infant born to mother of mirror syndrome secondary to fetomaternal hemorrhage: a case report.

BACKGROUND: Mirror syndrome (MS) is defined as maternal edema with fetal hydrops and placental edema with different etiologies, such as rhesus isoimmunization and twin-twin transfusion syndrome. Herein, we showcased a unique MS case secondary to fetomaternal hemorrhage (FMH). CASE PRESENTATION: A 32-year-old gravida 2 para 0 woman diagnosed with fetal hydrops was admitted to our hospital. Maternal laboratory tests revealed anemia, slightly increased creatinine and uric acid levels, hypoproteinemia, and significantly increased alpha-fetoprotein and hemoglobin-F levels. Therefore, FMH was diagnosed initially. Two days after admission, the woman had unexpectedly progressive anasarca and started to feel chest distress, palpitations, lethargy, and oliguria, and MS was suspected. An emergency cesarean section was performed to terminate the pregnancy. The maternal clinical symptoms and laboratory tests rapidly improved after delivery. A very preterm infant with a 2080-g birthweight at 31 weeks gestation survived after emergency cesarean section, active resuscitation, emergency blood transfusion, abdominocentesis, and advanced life support. CONCLUSIONS: FMH could develop into MS, providing new insights into the etiology of MS. Once MS is diagnosed, emergency cesarean section might be an alternative treatment. The very preterm infant survived with a favorable long-term outcome, and a well-trained perinatal work team is needed for such cases.

Identification and characterization of circular RNAs in mammary gland tissue from sheep at peak lactation and during the nonlactating period.

Circular RNAs are a class of noncoding RNA with a widespread occurrence in eukaryote tissues, and with some having been demonstrated to have clear biological function. In sheep, little is known about the role of circular RNAs in mammary gland tissue, and therefore an RNA sequencing approach was used to compare mammary gland tissue expression of circular RNAs in 9 Small Tail Han sheep at peak lactation, and subsequently when they were not lactating. These 9 sheep had their RNA pooled for analysis into 3 libraries from peak lactation and 3 from the nonlactating period. A total of 3,278 and 1,756 circular RNAs were identified in the peak lactation and nonlactating mammary gland tissues, respectively, and the expression and identity of 9 of them was confirmed using reverse transcriptase-polymerase chain reaction analysis and DNA sequencing. The type, chromosomal location and length of the circular RNAs identified were ascertained. Forty upregulated and one downregulated circular RNAs were characterized in the mammary gland tissue at peak lactation compared with the nonlactating mammary gland tissue. Gene ontology enrichment analysis revealed that the parental genes of these differentially expressed circular RNAs were related to molecular function, binding, protein binding, ATP binding, and ion binding. Five differentially expression circular RNAs were selected for further analysis to predict their target microRNAs, and some microRNAs reportedly associated with the development of the mammary gland were found in the constructed circular RNA-microRNA network. This study reveals the expression profiles and characterization of circular RNAs at 2 key stages of mammary gland activity, thereby providing an improved understanding of the roles of circular RNAs in the mammary gland of sheep.

Identification and characterization of circular RNA in lactating mammary glands from two breeds of sheep with different milk production profiles using RNA-Seq.

CircRNA is a specific type of non-coding RNA that has been shown to have an important role in mammary gland (MG) activity, but no study of MG circRNA activity in sheep so far. In this study, the expression profile of circRNAs was investigated using RNA-Seq in MG parenchyma at peak lactation from Small-Tailed Han sheep and Gansu Alpine Merino sheep with phenotypic differences in milk yield and components. A total of 4, 906 circRNAs were found and 33 of these were differentially expressed between breeds. GO and KEGG results showed that the parental genes of differentially expressed circRNAs were mainly enriched in heterocyclic compound binding, kinase activity, adherens junction, the TGF-ß signaling pathway, and the MAPK signaling pathway. This study provides an overview of circRNA expression in the ovine MG and the interaction between some key circRNAs and their target miRNAs. It improves our knowledge of the role of circRNA in sheep milk synthesis.

Cellular Nanosponges Inhibit SARS-CoV-2 Infectivity.

We report cellular nanosponges as an effective medical countermeasure to the SARS-CoV-2 virus. Two types of cellular nanosponges are made of the plasma membranes derived from human lung epithelial type II cells or human macrophages. These nanosponges display the same protein receptors, both identified and unidentified, required by SARS-CoV-2 for cellular entry. It is shown that, following incubation with the nanosponges, SARS-CoV-2 is neutralized and unable to infect cells. Crucially, the nanosponge platform is agnostic to viral mutations and potentially viral species, as well. As long as the target of the virus remains the identified host cell, the nanosponges will be able to neutralize the virus.

The Complexity of the Ovine and Caprine Keratin-Associated Protein Genes.

Sheep (Ovis aries) and goats (Capra hircus) have, for more than a millennia, been a source of fibres for human use, be it for use in clothing and furnishings, for insulation, for decorative and ceremonial purposes, or for combinations thereof. While use of these natural fibres has in some respects been superseded by the use of synthetic and plant-based fibres, increased accounting for the carbon and water footprint of these fibres is creating a re-emergence of interest in fibres derived from sheep and goats. The keratin-associated proteins (KAPs) are structural components of wool and hair fibres, where they form a matrix that cross-links with the keratin intermediate filaments (KIFs), the other main structural component of the fibres. Since the first report of a complete KAP protein sequence in the late 1960s, considerable effort has been made to identify the KAP proteins and their genes in mammals, and to ascertain how these genes and proteins control fibre growth and characteristics. This effort is ongoing, with more and more being understood about the structure and function of the genes. This review consolidates that knowledge and suggests future directions for research to further our understanding.

[Risk factors for endotracheal intubation during resuscitation in the delivery room among very preterm infants].

OBJECTIVE: To explore the risk factors for endotracheal intubation during resuscitation in the delivery room among very preterm infants. METHODS: A retrospective analysis was performed for 455 very preterm infants who were admitted to the neonatal intensive care unit from January 2017 to December 2019. They were divided into an intubation group (n=79) and a non-intubation group (n=376) according to whether endotracheal intubation was performed during resuscitation. The risk factors for endotracheal intubation during resuscitation were evaluated by multivariate logistic regression analysis. RESULTS: The intubation rate was 17.4% (79/455). Compared with the intubation group, the non-intubation group had significantly higher gestational age, birth weight, and rates of caesarean birth, delayed cord clamping (DCC), resuscitation quality improvement, regular use of antenatal glucocorticoids in mothers and premature rupture of membranes > 18 hours (P < 0.05), but significantly lower rates of maternal gestational diabetes mellitus, placental abruption, placenta previa or placenta previa status, and maternal thyroid dysfunction (P < 0.05). Regular use of antenatal glucocorticoids in mothers (OR=0.368, P < 0.05) and DCC (OR=0.222, P < 0.05) were protective factors against intubation during resuscitation, while younger gestational age, birth weight < 750 g, maternal gestational diabetes mellitus, and placenta previa or placenta previa status were risk factors for intubation during resuscitation (P < 0.05). CONCLUSIONS: Very preterm infants with younger gestational age, birth weight < 750 g, maternal diabetes mellitus, placenta previa or placenta previa status may have a higher risk for endotracheal intubation after birth. The regular use of antenatal glucocorticoids and DCC can reduce the risk of intubation during resuscitation in very preterm infants.

Correction to: FastMM: an efficient toolbox for personalized constraint-based metabolic modeling.

An amendment to this paper has been published and can be accessed via the original article.

FastMM: an efficient toolbox for personalized constraint-based metabolic modeling.

BACKGROUND: Constraint-based metabolic modeling has been applied to understand metabolism related disease mechanisms, to predict potential new drug targets and anti-metabolites, and to identify biomarkers of complex diseases. Although the state-of-art modeling toolbox, COBRA 3.0, is powerful, it requires substantial computing time conducting flux balance analysis, knockout analysis, and Markov Chain Monte Carlo (MCMC) sampling, which may limit its application in large scale genome-wide analysis. RESULTS: Here, we rewrote the underlying code of COBRA 3.0 using C/C++, and developed a toolbox, termed FastMM, to effectively conduct constraint-based metabolic modeling. The results showed that FastMM is 2~400 times faster than COBRA 3.0 in performing flux balance analysis and knockout analysis and returns consistent outputs. When applied to MCMC sampling, FastMM is 8 times faster than COBRA 3.0. FastMM is also faster than some efficient metabolic modeling applications, such as Cobrapy and Fast-SL. In addition, we developed a Matlab/Octave interface for fast metabolic modeling. This interface was fully compatible with COBRA 3.0, enabling users to easily perform complex applications for metabolic modeling. For example, users who do not have deep constraint-based metabolic model knowledge can just type one command in Matlab/Octave to perform personalized metabolic modeling. Users can also use the advance and multiple threading parameters for complex metabolic modeling. Thus, we provided an efficient and user-friendly solution to perform large scale genome-wide metabolic modeling. For example, FastMM can be applied to the modeling of individual cancer metabolic profiles of hundreds to thousands of samples in the Cancer Genome Atlas (TCGA). CONCLUSION: FastMM is an efficient and user-friendly toolbox for large-scale personalized constraint-based metabolic modeling. It can serve as a complementary and invaluable improvement to the existing functionalities in COBRA 3.0. FastMM is under GPL license and can be freely available at GitHub site: https://github.com/GonghuaLi/FastMM.