[Alterations in the intestinal microbiota of preterm infants with neurodevelopmental impairments: a prospective cohort study]. / ç¥žç»å‘è‚²æŸå®³æ—©äº§å„¿è‚ é“èŒç¾¤å˜åŒ–çš„å‰çž»æ€§é˜Ÿåˆ—ç ”ç©¶.

OBJECTIVES: To investigate the difference in intestinal microbiota between preterm infants with neurodevelopmental impairment (NDI) and those without NDI. METHODS: In this prospective cohort study, the preterm infants who were admitted to the neonatal intensive care unit of Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region from September 1, 2019 to September 30, 2021 were enrolled as subjects. According to the assessment results of Gesell Developmental Scale at the corrected gestational age of 1.5-2 years, they were divided into two groups: normal (n=115) and NDI (n=100). Fecal samples were collected one day before discharge, one day before introducing solid food, and at the corrected gestational age of 1 year. High-throughput sequencing was used to compare the composition of intestinal microbiota between groups. RESULTS: Compared with the normal group, the NDI group had a significantly higher Shannon diversity index at the corrected gestational age of 1 year (P<0.05). The principal coordinate analysis showed a significant difference in the composition of intestinal microbiota between the two groups one day before introducing solid food and at the corrected gestational age of 1 year (P<0.05). Compared with the normal group, the NDI group had a significantly higher abundance of Bifidobacterium in the intestine at all three time points, a significantly higher abundance of Enterococcus one day before introducing solid food and at the corrected gestational age of 1 year, and a significantly lower abundance of Akkermansia one day before introducing solid food (P<0.05). CONCLUSIONS: There are significant differences in the composition of intestinal microbiota between preterm infants with NDI and those without NDI. This study enriches the data on the characteristics of intestinal microbiota in preterm infants with NDI and provides reference for the microbiota therapy and intervention for NDI in preterm infants.

Mannose phosphate isomerase gene mutation leads to a congenital disorder of glycosylation: A rare case report and literature review.

We report the case of a 2-year-old girl who was diagnosed with Mannose-6-phosphate isomerase-congenital disorder of glycosylation (MPI-CDG) and provide a review of the relevant literature. The young girl presented with recurrent unexplained diarrhea, vomiting, hypoproteinemia, and elevated liver transaminases. Whole-exome sequencing revealed that the patient had compound heterozygous mutations in the MPI gene (NM_0024). An exon 4 (c.455G > T, p.R152l) mutation was inherited from the mother and an exon 7 (c.884G > A, p.R295H) mutation from the father. One week after the start of mannose treatment, the vomiting and diarrhea symptoms disappeared completely and did not show any side effects. We also provide a brief review of the relevant literature. Including the present case, a total of 52 patients from hospitals across 17 countries were diagnosed with MPI-CDG. Age at disease onset ranged from birth to 15 years, with an onset under 2 years in most patients (43/50). Overall, patients presented with at least one or more of the following symptoms: chronic diarrhea (41/46), vomiting (23/27), hepatomegaly (39/44), hepatic fibrosis (20/37), protein-losing enteropathy (30/36), elevated serum transaminases (24/34), hyperinsulinemic-hypoglycemia (24/34), hypoalbuminemia (33/38), prolonged coagulation (26/30), splenomegaly (13/21), non-pitting edema (14/20), failure to thrive (13/36), portal hypertension (4/9), epilepsy (2/17), thrombosis (12/14), and abnormally elevated leukocytes (5). None of the patients was reported to have an intellectual disability (0/28). The majority of patients (26/30) showed clinical symptoms, and laboratory results improved after oral mannose administration. Our findings suggest that MPI-CDG should be considered in children with unexplained recurrent digestive and endocrine systems involvement, and gene examination should be performed immediately to obtain a definite diagnosis in order to begin treatment in a timely manner.

Optimization of an Intranasal Route for the Delivery of Human Neural Stem Cells to Treat a Neonatal Hypoxic-Ischemic Brain Injury Rat Model.

Objective: Stem cell administration via the intranasal route has shown promise as a new therapy for hypoxic-ischemic encephalopathy (HIE). In this study, we aimed to improve the intranasal delivery of stem cells to the brain. Methods: Human neural stem cells (hNSCs) were identified using immunofluorescence, morphological, and flow cytometry assays before transplantation, and cell migration capacity was examined using the transwell assay. Cerebral hypoxia-ischemia (HI) was induced in 7-day-old rats, followed by the intranasal transplantation of CM-Dil-labeled hNSCs. We examined various experimental conditions, including preconditioning hNSCs with hypoxia, catheter method, multiple low-dose transplantation, head position, cell appropriate concentration, and volume. Rats were sacrificed 1 or 3 days after the final intranasal administration, and parts of the nasal tissue and whole brain sections were analyzed under a fluorescence microscope. Results: The isolated hNSCs met the characteristics of neural stem cells. Hypoxia (5% O2, 24 h) enhanced the surface expression of CXC chemokine receptor 4 (CXCR4) (9.21 ± 1.9% ~ 24.76 ± 2.24%, P < 0.01) on hNSCs and improved migration (toward stromal cell-derived factor 1 [SDF-1], 0.54 ± 0.11% ~ 8.65 ± 1.76%, P < 0.001; toward fetal bovine serum, 8.36 ± 0.81% ~ 21.74 ± 0.85%, P < 0.0001). Further improvement increased the number of surviving cell distribution with increased uniformity on the olfactory epithelium and allowed the cells to stay in the nasal cavity for at least 72 h, but they did not survive for longer than 48 h. Optimization of pre-transplantation conditions augmented the success rate of intranasally delivered cells to the brain (0-41.6%). We also tentatively identified that hNSCs crossed the olfactory epithelium into the tissue space below the lamina propria, with cerebrospinal fluid entering the cribriform plate into the subarachnoid space, and then migrated toward injured areas along the brain blood vessels. Conclusion: This study offers some helpful advice and reference for addressing the problem of repeatability in the intranasal delivery of stem cells.

Bacterial endotoxin-induced maternal inflammation leads to fetal intestinal injury and affects microbial colonization in the neonatal period.

BACKGROUND: Intraamniotic infection is associated with an increased risk of multiple adverse outcomes in offspring, especially neonatal necrotizing enterocolitis (NEC), which is one of the serious gastrointestinal diseases in neonates. However, the underlying mechanism remains undefined. We hypothesize that bacterial endotoxin-induced maternal inflammation causes intestinal injury in offspring, thereby affecting the composition of the intestinal microbiome. METHODS: Pregnant Sprague Dawley rats were received intraperitoneal injections with 700 µg/kg lipopolysaccharide (LPS, which was the same as bacterial endotoxin) or saline at 15 days of gestation. Pups were allowed to deliver naturally and euthanized at days 0, 3 and 7 after birth. Intestinal tissue and feces samples from offspring were collected to evaluate the effects of maternal inflammation on intestinal flora colonization and intestinal mucosal development. RESULTS: Significant intestinal injury of the offspring induced by prenatal LPS exposure was observed on day 0 and 3 after birth. In addition, prenatal LPS exposure also induced significant changes in the intestinal microbiome of the offspring with a significant increase in Proteobacteria (Escherichia-Shigella) and a decrease in Firmicutes at 7 days after birth. CONCLUSIONS: Thus, our findings suggest that LPS-induced maternal inflammation induces intestinal injury in offspring and subsequently leads to NEC-like changes in the composition of the intestinal microbiome.

Transplanted Human Oligodendrocyte Progenitor Cells Restore Neurobehavioral Deficits in a Rat Model of Preterm White Matter Injury.

Background: Preterm white matter injury (PWMI) is a common brain injury and a leading cause of life-long neurological deficits in premature infants; however, no effective treatment is available yet. This study aimed to investigate the fate and effectiveness of transplanted human oligodendrocyte progenitor cells (hOPCs) in a rat model of PWMI. Methods: Hypoxia-ischemia was induced in rats at postnatal day 3, and hOPCs (6 × 105 cells/5 µL) were intracerebroventricularly transplanted at postnatal day 7. Neurobehavior was assessed 12 weeks post-transplant using the CatWalk test and Morris water maze test. Histological analyses, as well as immunohistochemical and transmission electron microscopy, were performed after transcardial perfusion. Results: Transplanted hOPCs survived for 13 weeks in PWMI brains. They were widely distributed in the injured white matter, and migrated along the corpus callosum to the contralateral hemisphere. Notably, 82.77 ± 3.27% of transplanted cells differentiated into mature oligodendrocytes, which produced myelin around the axons. Transplantation of hOPCs increased the fluorescence intensity of myelin basic protein and the thickness of myelin sheaths as observed in immunostaining and transmission electron microscopy, while it reduced white matter atrophy at the level of gross morphology. With regard to neurobehavior, the CatWalk test revealed improved locomotor function and inter-paw coordination after transplantation, and the cognitive functions of hOPC-transplanted rats were restored as revealed by the Morris water maze test. Conclusions: Myelin restoration through the transplantation of hOPCs led to neurobehavioral improvements in PWMI rats, suggesting that transplanting hOPCs may provide an effective and promising therapeutic strategy in children with PWMI.

Identifying the functions of two biomarkers in human oligodendrocyte progenitor cell development.

BACKGROUND: Human oligodendrocyte precursor cells (hOPCs) are an important source of myelinating cells for cell transplantation to treat demyelinating diseases. Myelin oligodendrocytes develop from migratory and proliferative hOPCs. It is well known that NG2 and A2B5 are important biological markers of hOPCs. However, the functional differences between the cell populations represented by these two biomarkers have not been well studied in depth. OBJECTIVE: To study the difference between NG2 and A2B5 cells in the development of human oligodendrocyte progenitor cells. METHODS: Using cell sorting technology, we obtained NG2+/-, A2B5+/- cells. Further research was then conducted via in vitro cell proliferation and migration assays, single-cell sequencing, mRNA sequencing, and cell transplantation into shiverer mice. RESULTS: The proportion of PDGFR-α + cells in the negative cell population was higher than that in the positive cell population. The migration ability of the NG2+/-, A2B5+/- cells was inversely proportional to their myelination ability. The migration, proliferation, and myelination capacities of the negative cell population were stronger than those of the positive cell population. The ability of cell migration and proliferation of the four groups of cells from high to low was: A2B5- > NG2- > NG2+ > A2B5+. The content of PDGFR-α+ cells and the ability of cell differentiation from high to low was: NG2- > A2B5- > A2B5+ > NG2+. CONCLUSION: In summary, NG2+ and A2B5+ cells have poor myelination ability due to low levels of PDGFR-α+ cells. Therefore, hOPCs with a higher content of PDGFR-α+ cells may have a better effect in the cell transplantation treatment of demyelinating diseases.

Study on the Safety of Human Oligodendrocyte Precursor Cell Transplantation in Young Animals and Its Efficacy on Myelination.

Oligodendrocyte precursor cells (OPCs) can differentiate into myelinating oligodendrocytes during embryonic development, thereby representing an important potential source for myelin repair or regeneration. To the best of our knowledge, there are very few OPCs from human sources (human-derived OPCs [hOPCs]). In this study, we aimed to evaluate the safety and remyelination capacity of hOPCs developed in our laboratory, transplanted into the lateral ventricles of young animals. Several acute and chronic toxicity experiments were conducted in which different doses of hOPCs were transplanted into the lateral ventricles of Sprague-Dawley rats of different ages. The toxicity, biodistribution, and tumor formation ability of the injected hOPCs were examined by evaluating the rats' vital signs, developmental indicators, neural reflexes, as well as by hematology, immunology, and pathology. In addition, the hOPCs were transplanted into the corpus callosum of the shiverer mouse to verify cell myelination efficacy. Overall, our results show that transplanted hOPCs into young mice are nontoxic to their organ function or immune system. The transplanted cells engrafted in the brain and did not appear in other organs, nor did they cause tissue proliferation or tumor formation. In terms of efficacy, the transplanted hOPCs were able to form myelin in the corpus callosum, alleviate the trembling phenotype of shiverer mice, and promote normal development. The transplantation of hOPCs is safe; they can effectively form myelin in the brain, thereby providing a theoretical basis for the future clinical transplantation of hOPCs.

Effects of ß-Lactam Antibiotics on Gut Microbiota Colonization and Metabolites in Late Preterm Infants.

We usually refer to the critical period for intestinal flora establishment as infancy because the infant gut microbiota is characterized by low diversity and poor stability compared with that of adults. Moreover, it is also vulnerable to interference from a variety of factors. As ß-lactam antibiotics are typically used in newborn infants with infectious diseases, we used 16S rDNA sequencing and LC-MS metabolomics to analyze fecal microbes and metabolites in 16 late preterm infants with or without ß-lactam antibiotic treatment. The subjects were assigned to two groups: one not treated with antibiotics and another receiving ß-lactam antibiotic treatment for less than seven days. Significant changes in fecal microbes and metabolites were observed in the late preterm infants treated with antibiotics, including a reduction in the diversity of the gut microbiota overall and some beneficial bacteria such as Bacteroides, whereas some opportunistic pathogenic bacteria such as Enterococcus showed an overgrowth trend. In addition, significant changes in some crucial metabolites were observed, such as amino acids and bile acids. These findings show that treatment with ß-lactam antibiotics might affect the intestinal flora and its metabolites in late preterm infants in a short time period.

HKF-SVR Optimized by Krill Herd Algorithm for Coaxial Bearings Performance Degradation Prediction.

In real industrial applications, bearings in pairs or even more are often mounted on the same shaft. So the collected vibration signal is actually a mixed signal from multiple bearings. In this study, a method based on Hybrid Kernel Function-Support Vector Regression (HKF-SVR) whose parameters are optimized by Krill Herd (KH) algorithm was introduced for bearing performance degradation prediction in this situation. First, multi-domain statistical features are extracted from the bearing vibration signals and then fused into sensitive features using Kernel Joint Approximate Diagonalization of Eigen-matrices (KJADE) algorithm which is developed recently by our group. Due to the nonlinear mapping capability of the kernel method and the blind source separation ability of the JADE algorithm, the KJADE could extract latent source features that accurately reflecting the performance degradation from the mixed vibration signal. Then, the between-class and within-class scatters (SS) of the health-stage data sample and the current monitored data sample is calculated as the performance degradation index. Second, the parameters of the HKF-SVR are optimized by the KH (Krill Herd) algorithm to obtain the optimal performance degradation prediction model. Finally, the performance degradation trend of the bearing is predicted using the optimized HKF-SVR. Compared with the traditional methods of Back Propagation Neural Network (BPNN), Extreme Learning Machine (ELM) and traditional SVR, the results show that the proposed method has a better performance. The proposed method has a good application prospect in life prediction of coaxial bearings.

A Feature Extraction Method Using Improved Multi-Scale Entropy for Rolling Bearing Fault Diagnosis.

A feature extraction method named improved multi-scale entropy (IMSE) is proposed for rolling bearing fault diagnosis. This method could overcome information leakage in calculating the similarity of machinery systems, which is based on Pythagorean Theorem and similarity criterion. Features extracted from bearings under different conditions using IMSE are identified by the support vector machine (SVM) classifier. Experimental results show that the proposed method can extract the status information of the bearing. Compared with the multi-scale entropy (MSE) and sample entropy (SE) methods, the identification accuracy of the features extracted by IMSE is improved as well.

Vision-based measurement for rotational speed by improving Lucas-Kanade template tracking algorithm.

Rotational angle and speed are important parameters for condition monitoring and fault diagnosis of rotating machineries, and their measurement is useful in precision machining and early warning of faults. In this study, a novel vision-based measurement algorithm is proposed to complete this task. A high-speed camera is first used to capture the video of the rotational object. To extract the rotational angle, the template-based Lucas-Kanade algorithm is introduced to complete motion tracking by aligning the template image in the video sequence. Given the special case of nonplanar surface of the cylinder object, a nonlinear transformation is designed for modeling the rotation tracking. In spite of the unconventional and complex form, the transformation can realize angle extraction concisely with only one parameter. A simulation is then conducted to verify the tracking effect, and a practical tracking strategy is further proposed to track consecutively the video sequence. Based on the proposed algorithm, instantaneous rotational speed (IRS) can be measured accurately and efficiently. Finally, the effectiveness of the proposed algorithm is verified on a brushless direct current motor test rig through the comparison with results obtained by the microphone. Experimental results demonstrate that the proposed algorithm can extract accurately rotational angles and can measure IRS with the advantage of noncontact and effectiveness.

Online Doppler Effect Elimination Based on Unequal Time Interval Sampling for Wayside Acoustic Bearing Fault Detecting System.

The railway occupies a fairly important position in transportation due to its high speed and strong transportation capability. As a consequence, it is a key issue to guarantee continuous running and transportation safety of trains. Meanwhile, time consumption of the diagnosis procedure is of extreme importance for the detecting system. However, most of the current adopted techniques in the wayside acoustic defective bearing detector system (ADBD) are offline strategies, which means that the signal is analyzed after the sampling process. This would result in unavoidable time latency. Besides, the acquired acoustic signal would be corrupted by the Doppler effect because of high relative speed between the train and the data acquisition system (DAS). Thus, it is difficult to effectively diagnose the bearing defects immediately. In this paper, a new strategy called online Doppler effect elimination (ODEE) is proposed to remove the Doppler distortion online by the introduced unequal interval sampling scheme. The steps of proposed strategy are as follows: The essential parameters are acquired in advance. Then, the introduced unequal time interval sampling strategy is used to restore the Doppler distortion signal, and the amplitude of the signal is demodulated as well. Thus, the restored Doppler-free signal is obtained online. The proposed ODEE method has been employed in simulation analysis. Ultimately, the ODEE method is implemented in the embedded system for fault diagnosis of the train bearing. The results are in good accordance with the bearing defects, which verifies the good performance of the proposed strategy.

Note: On-line weak signal detection via adaptive stochastic resonance.

We design an instrument with a novel embedded adaptive stochastic resonance (SR) algorithm that consists of a SR module and a digital zero crossing detection module for on-line weak signal detection in digital signal processing applications. The two modules are responsible for noise filtering and adaptive parameter configuration, respectively. The on-line weak signal detection can be stably achieved in seconds. The prototype instrument exhibits an advance of 20 dB averaged signal-to-noise ratio and 5 times averaged adjust R-square as compared to the input noisy signal, in considering different driving frequencies and noise levels.

Note: signal amplification and filtering with a tristable stochastic resonance cantilever.

This Note reports a tristable cantilever that exploits stochastic resonance (SR) phenomenon for a study of signal amplification and filtering. The tristable device system combines the benefits of bistable system (wide interwell spacing) and monostable system (smooth motion in potential). The prototype tristable cantilever exhibits 42 times root-mean-square amplitude, 35.86 dB power gain, advance of 15 dB signal-to-noise ratio, and twice fidelity at around 7.6 Hz as compared to the input signal. In a wide operating bandwidth [5.5 Hz, 8.2 Hz], the tristable SR cantilever outperforms the traditional monostable cantilever and bistable SR cantilever in these characteristics.