Clinical application of bronchoalveolar lavage fluid metagenomics next-generation sequencing in cancer patients with severe pneumonia.

OBJECTIVE: Metagenomic next-generation sequencing (mNGS), as an emerging technique for pathogen detection, has been widely used in clinic. However, reports on the application of mNGS in cancer patients with severe pneumonia remain limited. This study aims to evaluate the diagnostic performance of bronchoalveolar lavage fluid (BALF) mNGS in cancer patients complicated with severe pneumonia. METHODS: A total of 62 cancer patients with severe pneumonia simultaneously received culture and mNGS of BALF were enrolled in this study. We systematically analyzed the diagnostic significance of BALF mNGS. Subsequently, optimization of anti-infective therapy based on the distribution of pathogens obtained from BALF mNGS was also assessed. RESULTS: For bacteria and fungi, the positive detection rate of mNGS was significantly higher than culture method (91.94% versus 51.61%, P < 0.001), especially for poly-microbial infections (70.97% versus 12.90%, P < 0.001). Compared with the culture method, mNGS exhibited a diagnostic sensitivity of 100% and a specificity of 16.67%, with the positive predictive value (PPV) and negative predictive value (NPV) being 56.14% and 100%, respectively. The agreement rate between these two methods was 59.68%, whereas kappa consensus analysis indicated a poor concordance (kappa = 0.171). After receipt of BALF mNGS results, anti-infective treatment strategies in 39 out of 62 cases (62.90%) were optimized. Moreover, anti-tumor therapy was a high-risk factor for mixed infections (87.18% versus 65.22%, P = 0.04). CONCLUSIONS: The present study showed that cancer patients with severe pneumonia, especially those received anti-tumor therapy, were more likely to have poly-microbial infections. BALF mNGS can provide a rapid and comprehensive pathogen distribution of pulmonary infection, making it a promising technique in clinical practice, especially for optimizing therapeutic strategies for cancer patients.

The influence of childhood emotional neglect experience on brain dynamic functional connectivity in young adults.

Background: Childhood emotional neglect (CEN) confers a great risk for developing multiple psychiatric disorders; however, the neural basis for this association remains unknown. Using a dynamic functional connectivity approach, this study aimed to examine the effects of CEN experience on functional brain networks in young adults.Method: In total, 21 healthy young adults with CEN experience and 26 without childhood trauma experience were recruited. The childhood trauma experience was assessed using the childhood trauma questionnaire (CTQ), and eligible participants underwent resting-state functional MRI. Sliding windows and k-means clustering were used to identify temporal features of large-scale functional connectivity states (frequency, mean dwell time, and transition numbers).Result: Dynamic analysis revealed two separate connection states: state 1 was more frequent and characterized by extensive weak connections between the brain regions. State 2 was relatively infrequent and characterized by extensive strong connections between the brain regions. Compared to the control group, the CEN group had a longer mean dwell time in state 1 and significantly decreased transition numbers between states 1 and 2.Conclusion: The CEN experience affects the temporal properties of young adults' functional brain connectivity. Young adults with CEN experience tend to be stable in state 1 (extensive weak connections between the brain regions), reducing transitions between states, and reflecting impaired metastability or functional network flexibility.

We focus solely on the childhood emotional neglect experience and its long-term effects on brain function.Eligible participants with and without childhood emotional neglect were identified through a large-scale screen among young adults.The results found childhood emotional neglect experiences have a long-term impact on brain flexibility.

Alterations in white matter integrity and network topological properties are associated with a decrease in global motion perception in older adults.

Previous studies have mainly explored the effects of structural and functional aging of cortical regions on global motion sensitivity in older adults, but none have explored the structural white matter (WM) substrates underlying the age-related decrease in global motion perception (GMP). In this study, random dot kinematogram and diffusion tensor imaging were used to investigate the effects of age-related reductions in WM fiber integrity and connectivity across various regions on GMP. We recruited 106 younger adults and 94 older adults and utilized both tract-based spatial statistics analysis and graph theoretical analysis to comprehensively investigate group differences in WM microstructural and network connections between older and younger adults at the microscopic and macroscopic levels. Moreover, partial correlation analysis was used to explore the relationship between alterations in WM and the age-related decrease in GMP. The results showed that decreased GMP in older adults was related to decreased fractional anisotropy (FA) of the inferior frontal-occipital fasciculus, inferior longitudinal fasciculus, anterior thalamic radiation, superior longitudinal fasciculus, and cingulum cingulate gyrus. Decreased global efficiency of the WM structural network and increased characteristic path length were closely associated with decreased global motion sensitivity. These results suggest that the reduced GMP in older adults may stem from reduced WM integrity in specific regions of WM fiber tracts as well as decreased efficiency of information integration and communication between distant cortical regions, supporting the "disconnection hypothesis" of cognitive aging.

The relationship between childhood emotional neglect experience and depressive symptoms and prefrontal resting functional connections in college students: The mediating role of reappraisal strategy.

Childhood emotional neglect (CEN) has a relatively high incidence rate and substantially adverse effects. Many studies have found that CEN is closely related to emotion regulation and depression symptoms. Besides, the functional activity of the prefrontal lobe may also be related to them. However, the relationships between the above variables have not been thoroughly studied. This study recruited two groups of college students, namely, those with primary CEN (neglect group) and those without childhood trauma (control group), to explore the relationships among CEN, adulthood emotion regulation, depressive symptoms, and prefrontal resting functional connections. The methods used in this study included the Childhood Trauma Questionnaire (CTQ), Emotion Regulation Questionnaire (ERQ), Beck Depression Inventory-II (BDI-II) and resting-state functional magnetic resonance imaging (rs-fMRI). The results showed that compared with the control group, the neglect group utilized the reappraisal strategy less frequently and displayed more depressive symptoms. The prefrontal functional connections with other brain regions in the neglect group were more robust than those in the control group using less stringent multiple correction standards. Across the two groups, the functional connection strength between the right orbitofrontal gyrus and the right middle frontal gyrus significantly negatively correlated with the ERQ reappraisal score and positively correlated with the BDI-II total score; the ERQ reappraisal score wholly mediated the relationship between the functional connection strength and the BDI-II total score. It suggests that primary CEN may closely correlate with more depressive symptoms in adulthood. Furthermore, the more robust spontaneous activity of the prefrontal lobe may also be closely associated with more depressive symptoms by utilizing a reappraisal strategy less frequently.

Advances in the application of induced pluripotent stem cells in pediatric diseases.

The optimal diagnosis and treatment of pediatric diseases depend on more adequate understanding of pathophysiology. The advent of induced pluripotent stem cells (iPSCs) has provided new strategies for the research and therapy of pediatric diseases. iPSCs are pluripotent stem cells induced by reprogramming of mature cells. Now they can be induced from many types of somatic cells (such as fibroblasts, peripheral blood mononuclear cells and urine cells).With the improvement of various reprogramming methods, its generation procedure is more and more optimized, and the use of small molecules to induce iPSCs is one of the research focus now. Due to their ability to differentiate into a variety of cells, combined with the development of gene editing technology, iPSCs have been increasingly favored in the modeling of diseases and cell therapy, especially hereditary diseases, and have achieved some success in clinical treatment. But before they can be widely used in clinical treatment, there are still some problems to be solved, such as tumorigenicity, immunogenicity and heterogeneity. This article reviewed the source of iPSCs, reprogramming technology, applications of iPSCs in common childhood diseases, current problems and prospects, in order to deepen the understanding of iPSCs and provide reference for in-depth research in field of exploring mechanisms of diseases and therapy of diseases.

The structural basis of age-related decline in global motion perception at fast and slow speeds.

A decrease in global motion perception (GMP) has been reported in older adults, and this age-related decline in GMP varies with the speed of global motion. However, no studies have investigated whether the asynchronous age-related decline in GMP is related to degenerative changes in brain structure. In this study, the random dot kinematogram paradigm and structural magnetic resonance imaging were used to investigate the asynchronous aging of GMP at fast and slow speeds (called fast GMP and slow GMP, respectively) and their relationships with brain structure. Ninety-four older adults (65.74 ± 4.50 yrs) and 90 younger adults (22.83 ± 4.84 yrs) participated in the experiment. The results showed that older adults had higher motion coherence thresholds (MCT) than younger adults at both fast and slow speeds. Brain-behavior correlation analyses of younger adults revealed that none of the correlations between morphological measures and MCTs survived correction for multiple comparisons. For older adults, slow MCT was correlated with cortical thickness in the bilateral V4v, V5/MT+, left V7, V8, LO, and surface area in the right V7. Fast MCT was significantly correlated with gray matter volume in the right V7 and thickness in the left V5/MT+. These results support the view that global motion extraction occurs within two speed-tuned systems that are at least partially independent in terms of their neural substrates, which deteriorate with age at different speeds. Aging of GMP is also associated with morphological changes in the visual cortex. Age-related cerebral atrophy in the dorsal stream may impair both fast and slow GMP, whereas aging of the ventral stream specifically impairs slow GMP.

Metabolomic and transcriptomic exploration of the uric acid-reducing flavonoids biosynthetic pathways in the fruit of Actinidia arguta Sieb. Zucc.

Flavonoids from Actinidia arguta Sieb. Zucc. can reduce uric acid in mice. However, the molecular basis of its biosynthesis is still unclear. In this paper, we used a combination of extensively targeted metabolomics and transcriptomics analysis to determine the types and differences of flavonoids in the fruit ripening period (August to September) of two main cultivated varieties in northern China. The ethanol extract was prepared, and the potential flavonoids of Chrysin (Flavone1), Rutin (Flavone2), and Daidzein (Flavone3) in Actinidia arguta Sieb. Zucc. were separated and purified by HPD600 macroporous adsorption resin and preparative liquid chromatography. The structure was identified by MS-HPLC, and the serum uric acid index of male Kunming mice was determined by an animal model test.125 flavonoids and 50 differentially regulated genes were identified. The contents of UA (uric acid), BUN (urea nitrogen), Cr (creatinine), and GAPDH in mouse serum and mouse liver glycogen decreased or increased in varying degrees. This paper reveals the biosynthetic pathway of uric acid-reducing flavonoids in the fruit of Actinidia arguta Sieb. Zucc., a major cultivar in northern China, provides valuable information for the development of food and drug homologous functional foods.

Role of surfactant protein C in neonatal genetic disorders of the surfactant system: A case report.

RATIONALE: Respiratory distress syndrome (RDS) refers to the symptoms of progressive dyspnea and respiratory failure in newborns shortly after birth. The clinical and genetic characteristics of patients with neonatal RDS have not been extensively reported. PATIENT CONCERNS: A infant was in critical condition with repeated paroxysmal blood oxygen decline. Oxygen inhalation and noninvasive ventilator-assisted breathing relief were not effective. The etiology was unclear, and there was no family history of lung disease. Surface-active substance replacement therapy and positive pressure-assisted ventilation support were ineffective. DIAGNOSIS: The infant was clinically diagnosed with RDS. Genetic tests revealed a heterozygous missense mutation in the c.168 surfactant protein C (SFTPC) gene. INTERVENTIONS: Tracheal intubation was performed with invasive ventilator-assisted breathing, pulmonary surfactant was administered. Supportive treatment for liver protection and administration of a cardiotonic diuretic, vasodilator, human immunoglobulin (intravenous infusion), fresh frozen plasma, and suspended red blood cells were performed. OUTCOMES: The infant showed poor responses to respiratory and circulatory support, antibiotic treatment, and other treatment methods. The patient was discharged from hospital against the advice of us, cut off from us. The long-term prognosis of the patient after discharge remains unknown. LESSONS: SFTPC gene mutations may be an important risk factor for the development of common lung diseases. Because of the important roles of surfactant functions and metabolism, mutations in these genes can affect the production and function of pulmonary surfactant, leading to severe lung disease in term newborns.

Regulation of MYB Transcription Factors of Anthocyanin Synthesis in Lily Flowers.

Flower color is the decisive factor that affects the commercial value of ornamental flowers. Therefore, it is important to study the regulation of flower color formation in lily to discover the positive and negative factors that regulate this important trait. In this study, MYB transcription factors (TFs) were characterized to understand the regulatory mechanism of anthocyanin biosynthesis in lily. Two R2R3-MYB TFs, LvMYB5, and LvMYB1, were found to regulate anthocyanin biosynthesis in lily flowers. LvMYB5, which has an activation motif, belongs to the SG6 MYB protein subgroup of Arabidopsis thaliana. Transient expression of LvMYB5 indicated that LvMYB5 can promote coloration in Nicotiana benthamiana leaves, and that expression of LvMYB5 increases the expression levels of NbCHS, NbDFR, and NbANS. VIGS experiments in lily petals showed that the accumulation of anthocyanins was reduced when LvMYB5 was silenced. Luciferase assays showed that LvMYB5 can promote anthocyanin synthesis by activating the ANS gene promoter. Therefore, LvMYB5 plays an important role in flower coloration in lily. In addition, the transient expression experiment provided preliminary evidence that LvMYB1 (an R2R3-MYB TF) inhibits anthocyanin synthesis in lily flowers. The discovery of activating and inhibitory factors related to anthocyanin biosynthesis in lily provides a theoretical basis for improving flower color through genetic engineering. The results of our study provide a new direction for the further study of the mechanisms of flower color formation in lilies.

Generation of an induced pluripotent stem cell line from a patient with surfactant metabolism dysfunction carrying ABCA3 mutations.

Surfactant dysfunction is a genetically heterogeneous pulmonary disease that causes dyspnea. ATP binding cassette protein transporter subunit A3 (ABCA3) is the main pathogenic gene of pulmonary surfactant dysfunction. In this study, we established an induced pluripotent stem cell line (SMCPGHi001-A) from the peripheral blood cells of a 49-day-old male infant, carrying compound heterozygous variations of the ABCA3 gene (c.3997_3998del, p.R1333fs, and c.3137C > T, p.A1046V). This iPSC line would be a useful tool to study the pathogenesis, disease development, and treatment of pulmonary surfactant dysfunction.

Integrated metabolic profiling and transcriptome analysis of pigment accumulation in diverse petal tissues in the lily cultivar 'Vivian'.

BACKGROUND: Petals are the colorful region of many ornamental plants. Quality traits of petal color directly affect the value of ornamental plants. Although the regulatory mechanism of flower color has been widely studied in many plants, that of lily flower color is still worth further exploration. RESULTS: In this study, the pigmentation regulatory network in different regions of the petal of lily cultivar 'Vivian' was analyzed through tissue structure, metabolites biosynthesis, and gene expression. We found that cell morphology of the petal in un-pigmented region differed from that in pigmented region. The cell morphology tends to flatten in un-pigmented region where the color is lighter. Moreover, high level anthocyanin was found in the pigmented regions by metabonomic analysis, especially cyanidin derivatives. However, flavanones were accumulated, contrast with anthocyanin in the un-pigmented regions of lily petal. To understand the relationship of these different metabolites and lily flower color, RNA-Seq was used to analyze the differentially expressed genes-related metabolite biosynthesis. Among these genes, the expression levels of several genes-related cyanidin derivatives biosynthesis were significantly different between the pigmented and un-pigmented regions, such as LvMYB5, LvMYB7, LvF3'H, LvDFR, LvANS and Lv3GT. CONCLUSIONS: This data will help us to further understand the regulation network of lily petal pigmentation and create different unique color species.

Genome Comparison Reveals Mutation Hotspots in the Chloroplast Genome and Phylogenetic Relationships of Ormosia Species.

The papilionoid legume genus Ormosia comprises approximately 130 species, which are distributed mostly in the Neotropics, with some species in eastern Asia and northeastern Australia. The taxonomy and evolutionary history remain unclear due to the lack of a robust species-level phylogeny. Chloroplast genomes can provide important information for phylogenetic and population genetic studies. In this study, we determined the complete chloroplast genome sequences of five Ormosia species by Illumina sequencing. The Ormosia chloroplast genomes displayed the typical quadripartite structure of angiosperms, which consisted of a pair of inverted regions separated by a large single-copy region and a small single-copy region. The location and distribution of repeat sequences and microsatellites were determined. Comparative analyses highlighted a wide spectrum of variation, with trnK-rbcL, atpE-trnS-rps4, trnC-petN, trnS-psbZ-trnG, trnP-psaJ-rpl33, and clpP intron being the most variable regions. Phylogenetic analysis revealed that Ormosia is in the Papilionoideae clade and is sister to the Lupinus clade. Overall, this study, which provides Ormosia chloroplast genomic resources and a comparative analysis of Ormosia chloroplast genomes, will be beneficial for the evolutionary study and phylogenetic reconstruction of the genus Ormosia and molecular barcoding in population genetics and will provide insight into the chloroplast genome evolution of legumes.

Coagulation function and placental pathology in neonates with placental abruption.

This study aimed to investigate the coagulation function and placental pathology in neonates with placental abruption (PA). A total of 60 neonates with PA and 60 neonates without PA were recruited. Neonates with PA were further subdivided into mild and severe groups. Neonates with PA had a higher incidence of anemia and hypovolemic shock (P<0.05), and were more likely to develop metabolic acidosis, asphyxia, intracranial hemorrhage, hypoxic-ischemic myocardial injury, hypoxic-ischemic encephalopathy, and disseminated intravascular coagulation (P<0.05). They also had longer hospital stay (P=0.033). At 6 h, the prothrombin time (PT), activated partial thromboplastin time (APTT), and D-dimer (D-D) were higher (P<0.05), but fibrinogen (FIB) was lower (P=0.000) in PA neonates than in controls. Significant differences were observed in tissue factor (TF), tissue factor pathway inhibitor (TFPI), and TF/TFPI among the mild PA group, whereas the severe PA and control groups were observed among different time points (P<0.05), and during time-group interaction (P<0.05). Thus, PA may cause coagulation dysfunction in neonates. The larger the separation area, the more evident the coagulation dysfunction was. TF and TFPI are involved in the pathogenesis of coagulation dysfunction in PA neonates and early heparin intervention is effective to imporve coagulation function and prognosis.

Surfactant protein b expression in bronchoalveolar lavage fluid of full-term neonates with respiratory distress syndrome.

The aim was to investigate the surfactant protein B (SP-B) expression in the bronchoalveolar lavage fluid (BALF) of full-term neonates with respiratory distress syndrome (RDS). The enzyme-linked immunosorbent assay was performed to assess SP-B expression in BALF of 60 full-term neonates with RDS and 23 healthy neonates and correlation of SP-B level with RDS classification according to chest x-ray findings and PaO2/FiO2 before mechanical ventilation in neonates with RDS. The SP-B level was significantly lower in the RDS group (17.63 +/- 6.80 ng/mL) than in healthy neonates (103.95 +/- 6.38 ng/mL) (P < 0.001). The SP-B level correlated positively with PaO2/ FiO2 before mechanical ventilation (r = 0.838, P < 0.001). Moreover, the lower the SP-B level, the more severe was the RDS as determined by chest x-ray (P < 0.001). In conclusion, full-term neonates with RDS had reduced SP-B in BALF, which was related to the severity of RDS, suggesting that SP-B supplement may be an effective strategy in the treatment of RDS in full-term neonates.

Desferrioxamine regulates HIF-1 alpha expression in neonatal rat brain after hypoxia-ischemia.

Hypoxia-inducible factor 1α (HIF-1α) promotes cell survival after hypoxia-ischemia by regulating its target genes. Desferrioxamine (DFO) has been found to up-regulate HIF-1α expression in ischemia brain injury. However, the signaling pathway to mediate this regulation remains unclear in neonatal hypoxia-ischemia brain damage (HIBD). Since phosphoinositide 3-kinase (PI3K/Akt) pathway and extracellular signal-related protein kinase pathway (Erk1/2 MAPK) have proven to be involved in the regulation of HIF-1α in neonatal rat brain after hypoxia-ischemia (HI), we hypothesized that DFO might regulate HIF-1α by activating PI3K/Akt and Erk1/2 MAPK pathways in developing rat brain after HI. To test this hypothesis, we subjected postnatal day 10 rats to DFO intraperitoneal injection 30 min before HI. Rat brains were collected to detect the expression of HIF-1α and its target gene VEGF, as well as PI3K/Akt and Erk1/2 MAPK using Western blot analysis. We found that the expression of HIF-1α, VEGF, and p-Erk1/2 was significantly upregulated and peaked at 4 h after HI in DFO treated group, with higher level and earlier peak time than control group. However, the expression of p-Akt was unchanged in DFO treated group compared with control group. Our findings suggest that DFO might up-regulate HIF-1α and its target gene VEGF through Erk1/2 MAPK pathway in the developing rat brain after HI.

A novel silent deletion, an insertion mutation and a nonsense mutation in the TCOF1 gene found in two Chinese cases of Treacher Collins syndrome.

Treacher Collins syndrome (TCS) is the most common and well-known craniofacial disorder caused by mutations in the genes involved in pre-rRNA transcription, which include the TCOF1 gene. This study explored the role of TCOF1 mutations in Chinese patients with TCS. Mutational analysis of the TCOF1 gene was performed in three patients using polymerase chain reaction and direct sequencing. Among these three patients, two additional TCOF1 variations, a novel 18 bp deletion and a novel 1 bp insertion mutation, were found in patient 1, together with a novel nonsense mutation (p.Ser476X) and a previously reported 4 bp deletion (c.1872_1875delTGAG) in other patients. Pedigree analysis allowed for prediction of the character of the mutation, which was either pathological or not. The 18 bp deletion of six amino acids, Ser-Asp-Ser-Glu-Glu-Glu (798*803), which was located in the CKII phosphorylation site of treacle, seemed relatively benign for TCS. By contrast, another novel mutation of c.1072_1073insC (p.Gln358ProfsX23) was a frameshift mutation and expected to result in a premature stop codon. This study provides insights into the functional domain of treacle and illustrates the importance of clinical and family TCS screening for the interpretation of novel sequence alterations.

Value of amplitude-integrated electroencephalograph in early diagnosis and prognosis prediction of neonatal hypoxic-ischemic encephalopathy.

UNLABELLED: To investigate value of amplitude-integrated electroencephalograph (aEEG) in early diagnosis and prediction of long-term prognosis of neonatal hypoxic-ischemic encephalopathy (HIE), 120 HIE Children were randomly assigned into aEEG group and control group (n = 60 per group). Children in each group were sub-divided into mild, moderate and severe HIE groups (n = 20 per group). 1, 3, 14 and 28 days after birth, aEEG was performed in aEEG group; 3, 14 and 28 days after birth, neonatal behavioral neurological assessment (NBNA) was done in both groups. Children who discharged were followed up at adjusted gestational age of 12 months with Denver Developmental Screening Test (DDST) and prognosis evaluation. RESULTS: aEEG manifestation was positively related to clinical severityb of HIE (r = 0.843, P < 0.01). On day 3 and 14, NBNA score was comparable between two groups (P > 0.05), but significant difference in NBNA score was noted on day 28 (P < 0.05). On day 3, 14 and 28, aEEG manifestation was positively associated with prognosis at adjusted gestational age of 12 months (r = 0.832, 0.857, 0.778, 0.743, P < 0.01). In aEEG group, disability rate was 13.8%, which was significantly lower than that in control group (23.2%); cure rate in aEEG group (60%) was significantly higher than that in control group (40%). Moreover, long-term prognosis was also dramatically different between aEEG group and control group (χ(2) = 4.107, P < 0.05). CONCLUSION: aEEG manifestation is significantly associated with clinical severity of HIE and may be helpful for early diagnosis of HIE. aEEG may be used to predict long term prognosis of HIE children.

Development of neural stem cells at different sites of fetus brain of different gestational age.

OBJECTIVE: This study aimed to investigate the development of neural stem cells (NSCs) in fetal brain, which may provide experimental evidence for the clinical treatment of brain injury in children. METHODS: A total of 60 fetuses were collected after labor induction and divided into 6 groups according to the gestational age (16 w, 20 w, 24 w, 28 w, 32 w and 36 w; n=10 per group). The hippocampus, striatum, subventricular zone, frontal lobe, temporal lobe, occipital lobe and parietal lobe were harvested. In situ hybridization, immunohistochemistry and light microscopy were done to determine the morphology and quantity of NSCs. RESULTS: NSCs were identified in the brain of fetuses with different gestational age. NSCs were round, oval, spindle-shaped, starlike, triangular or polygonal. NSC colony was also observed with symmetrical or asymmetrical division. Single NSC, group-like NSCs and cluster-like NSCs were found in the different sites of fetal brain, and NCSs interacted with each other via synapses. However, the distribution, morphology, growth and quantity of NSCs were different in the brain of fetuses with different gestational age. The number of NSCs reduced with the increase in gestational age, but they were always observed. CONCLUSION: The morphology of NSCs in fetal brain is variable and they are widely distributed in the hippocampus, subventricular zone, striatum and cortex. The number of NSCs reduced with the increase of gestational age.

Role of mouse nerve growth factor in neural recovery following hypoxic-ischemic brain damage.

OBJECTIVE: To investigate the role of mouse nerve growth factor (mNGF) in neutral repair following hypoxic-ischemic brain damage (HIBD) in a neonatal rat model. METHODS: A total of 120 neonatal rats aged 7 days were randomly divided into control group, HIBD group and mNGF group (n=40 /group). Immediately after HIBD, mNGF was intramuscularly injected into rats in the mNGF group. 7, 14, 21 and 28 days after injection, immunohistochemistry and TUNEL staining were performed. RESULTS: In the HIBD group, Nestin expression was mainly found in the CA1, CA2 and CA3 regions of hippocampus. In the mNGF group, Nestin was mainly noted in the DG and CA3 regions. 7, 14 and 28 days after treatment, significant difference was found in the Nestin expression among three groups, but not observed 21 days after treatment. 21 and 28 days after treatment, the number of apoptotic neurons was markedly reduced when compared with that 7 and 14 days after treatment. CONCLUSION: mNGF can improve the neurogenesis and inhibit neural apoptosis in the hippocampus following HIBD in a neonatal rat model.

SACE_0012, a TetR-family transcriptional regulator, affects the morphogenesis of Saccharopolyspora erythraea.

Saccharopolyspora erythraea, a mycelium-forming actinomycete, produces a clinically important antibiotic erythromycin. Extensive investigations have provided insights into erythromycin biosynthesis in S. erythraea, but knowledge of its morphogenesis remains limited. By gene inactivation and complementation strategies, the TetR-family transcriptional regulator SACE_0012 was identified to be a negative regulator of mycelium formation of S. erythraea A226. Detected by quantitative real-time PCR, the relative transcription of SACE_7115, the amfC homolog for an aerial mycelium formation protein, was dramatically increased in SACE_0012 mutant, whereas erythromycin biosynthetic gene eryA, a pleiotropic regulatory gene bldD, and the genes SACE_2141, SACE_6464, SACE_6040, that are the homologs to the sporulation regulators WhiA, WhiB, WhiG, were not differentially expressed. SACE_0012 disruption could not restore its defect of aerial development in bldD mutant, and also did not further accelerate the mycelium formation in the mutant of SACE_7040 gene, that was previously identified to be a morphogenesis repressor. Furthermore, the transcriptional level of SACE_0012 had not markedly changed in bldD and SACE_7040 mutant over A226. Taken together, these results suggest that SACE_0012 is a negative regulator of S. erythraea morphogenesis by mainly increasing the transcription of amfC gene, independently of the BldD regulatory system.