Transcriptomic profiling of Dip2a in the neural differentiation of mouse embryonic stem cells.

Introduction: The disconnected-interacting protein 2 homolog A (DIP2A), a member of disconnected-interacting 2 protein family, has been shown to be involved in human nervous system-related mental illness. This protein is highly expressed in the nervous system of mouse. Mutation of mouse DIP2A causes defects in spine morphology and synaptic transmission, autism-like behaviors, and defective social novelty [5], [27], indicating that DIP2A is critical to the maintenance of neural development. However, the role of DIP2A in neural differentiation has yet to be investigated. Objective: To determine the role of DIP2A in neural differentiation, a neural differentiation model was established using mouse embryonic stem cells (mESCs) and studied by using gene-knockout technology and RNA-sequencing-based transcriptome analysis. Results: We found that DIP2A is not required for mESCs pluripotency maintenance, but loss of DIP2A causes the neural differentiation abnormalities in both N2B27 and KSR medium. Functional knockout of Dip2a gene also decreased proliferation of mESCs by perturbation of the cell cycle and profoundly inhibited the expression of a large number of neural development-associated genes which mainly enriched in spinal cord development and postsynapse assembly. Conclusions: The results of this report demonstrate that DIP2A plays an essential role in regulating differentiation of mESCs towards the neural fate.

Neutralizing monoclonal antibodies protect against human adenovirus type 55 infection in transgenic mice and tree shrews.

Re-emerging human adenovirus type 55 (HAdV55) has become a significant threat to public health due to its widespread circulation and the association with severe pneumonia, but an effective anti-HAdV55 agent remains unavailable. Herein, we report the generation of macaque-derived, human-like monoclonal antibodies (mAbs) protecting against HAdV55 infection with high potency. Using fluorophore-labelled HAdV55 virions as probes, we isolated specific memory B cells from rhesus macaques (Macaca mulatta) that were immunized twice with an experimental vaccine based on E1-, E3-deleted, replication-incompetent HAdV55. We cloned a total of 19 neutralizing mAbs, nine of which showed half-maximal inhibitory concentrations below 1.0 ng/ml. These mAbs recognized the hyper-variable-region (HVR) 1, 2, or 7 of viral hexon protein, or the fibre knob. In transgenic mice expressing human desmoglein-2, the major cellular receptor for HAdV55, a single intraperitoneal injection with hexon-targeting mAbs efficiently prevented HAdV55 infection, and mAb 29C12 showed protection at a dose as low as 0.004 mg/kg. Fibre-targeting mAb 28E8, however, showed protection only at a dose up to 12.5 mg/kg. In tree shrews that are permissive for HAdV55 infection and disease, mAb 29C12 effectively prevented HAdV55-caused pneumonia. Further analysis revealed that fibre-targeting mAbs blocked the attachment of HAdV55 to host cells, whereas hexon-targeting mAbs, regardless of their targeting HVRs, mainly functioned at post-attachment stage via inhibiting viral endosomal escape. Our results indicate that hexon-targeting mAbs have great anti-HAdV55 activities and warrant pre-clinical and clinical evaluation.

A Comparison between Thromboelastography and Conventional Clotting Tests in Pediatric Patients After Cardiopulmonary Bypass Procedure.

BACKGROUND: The coagulation system is more complicated in younger infants because the hemostatic system is not completely mature before 6 months. There is confusion among pediatricians to choose conventional coagulation tests and thromboelastography (TEG) to evaluate coagulation function for infants in major surgery. This study was undertaken to perform a comparison between the two methods for pediatric patients who underwent cardio-pulmonary bypass (CPB) surgery. METHODS: Infant patients who underwent CPB surgery were divided into two groups - younger group (age < 6 months old, n = 72) and older group (age from 6 months old to 12 years old, n = 76). Prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and fibrinogen (Fib) of conventional coagulation tests and reaction time (R-time), speed of fibrin building up (ɑ-Angle), clot conformation time (K-time), maximum colt amplitude (MA) of TEG results before and after CPB, as well as increasing or decreasing rate of all the values after CPB, were compared between the two groups. Postoperative transfusion details were summarized. RESULTS: PT, APTT, R-time, and K-time markedly increased (p < 0.05) and Fib, ɑ-Angle, and MA decreased (p < 0.05) after CPB in both groups. The younger group had a much higher rate of postoperative transfusion with suspended red cells (54.17% vs. 17.11%), fresh frozen plasma (29.17% vs. 9.21%), cryoprecipitate (9.72% vs. 1.32%), and apheresis platelet (5.56% vs. 0) than the older group. Increasing rate of R-time and K-time and decreasing rate of ɑ-Angle and MA after CPB in the younger group were significantly higher than that in the older group (p < 0.01), whereas no significant differences were observed in conventional coagulation tests (p > 0.2). CONCLUSIONS: TEG was more sensitive than conventional coagulation tests in response to variation of coagulation function for younger infants after major surgery.

The volatile release evaluation of nicotine from snus products under different storage conditions based on surface-enhanced Raman spectroscopy technology.

Surface enhanced Raman spectroscopy (SERS) is a highly sensitive analytical detection technique that provides unique chemical and structural information on target molecules. Snus is a type of tobacco product that can release nicotine and other components under certain humidity and temperature without burning, and the evaluation of its nicotine release under different storage conditions is very important for understanding its characteristics, regulating its components, and setting reasonable storage conditions. Herein, by means of an artificial climate box and suction extraction device, the volatile release evaluations of nicotine from snus products under different storage conditions were performed based on Fe3O4 microparticles coated with Au nanorods and Au nanoparticles (Fe3O4@AuNRsNPs) as SERS substrates combined with a capillary. The Fe3O4@AuNRsNPs assemblies can be fixed in the inner wall of the capillary with the aid of an external magnetic field, which improved the maneuverability of the SERS substrates. By comparing the intensities of the spectral peaks of the symmetrical breathing of the pyridine moiety of nicotine molecules with increasing temperature and humidity, which could significantly accelerate the volatile release of a small amount of nicotine, the nicotine release under different conditions could be evaluated. Based on this strategy, it was possible to obtain the storage or placement conditions of the product. The results of this study provide a reference to clarify the volatile release of nicotine under various storage conditions, which is helpful for better regulation of the levels of nicotine in snus. Moreover, such destruction-free evaluation of the volatile release of nicotine from snus products under different storage conditions opens up new perspectives for further research about the impact of nicotinoids on smokers' health and cessation programs.

Improvement of neurological recovery in the insomnia rats by Warming Yang Strategy through targeting SIRT4 by inhibiting inflammation and apoptosis.

The incidence rate of insomnia is increasing, but the mechanism of it remains unclear. Warming Yang Strategy (WY) is a kind of Traditional Chinese Medicine, and it is proved to be effective in treating insomnia patients. The insomnia animal was established with chlorophenylalanine (PCPA). Morris water maze and open field test were performed to evaluate the influence of WY on the neurological recovery of insomnia rats. TUNEL staining and flow cytometry were used to measure apoptosis level. WY promoted the neurological recovery in the insomnia rats through Morris water maze and open field test evaluation. The increase of γ-aminobutyric acid, dopamine, 5-hydroxytryptamine, and norepinephrine caused by WY was suppressed by siSIRT4. The decrease of apoptosis and inflammation factors expression induced by WY was promoted by siRNA-SIRT4 (siSIRT4). WY improve neurological recovery in the insomnia rats through SIRT4 by inhibiting inflammation and apoptosis. This research might provide a novel insight for the prevention and treatment of insomnia through targeting SIRT4.

Analogous plasmon-induced absorption based on an end-coupled MDM structure with area-cost-free cavities.

We theoretically investigate an end-coupled metal-dielectric-metal (MDM) structure that achieves analogous plasmon-induced absorption (APIA) in an area-cost-free manner. First, a squared ring is set to end-couple with MDM input and output waveguides, generating three Lorentzian-like peaks in the spectrum. Then, two APIA windows as well as two Fano resonances can be induced via appropriately arranging two area-free cavities. Numerous numerical results demonstrate that the proposed structure has remarkable sensing and phase characteristics. Our proposed PIA-based MDM structure is promising in potential applications of bio-chemical sensing, slow light devices, optical switching, and chip-scale plasmonic devices.

GC-MS combined with multivariate analysis for the determination of the geographical origin of Elsholtzia rugulosa Hemsl. in Yunnan province.

Elsholtzia rugulosa Hemsl., a Chinese herbal medicine, may have the potential to treat COVID-19. The geographical origin has a significant influence on the quality and application of E. rugulosa. In this paper, gas chromatography-mass spectrometry (GC-MS) combined with principal component analysis (PCA) and hierarchical cluster analysis (HCA) and other multivariate statistical analyses were performed for the identification of E. rugulosa. origins. The results showed that the volatile components of E. rugulosa. from different origins were significantly different. PCA and HCA can clearly distinguish the E. rugulosa of Lijiang and Fumin, and Dali and Yongsheng can be distinguished but with a certain overlap. The correlation of different components of was investigated by Pearson correlation. The results showed that E. rugulosa. characteristic component Elsholtzia ketone is regulated by terpenoid metabolism. The discriminant functions of different origins are constructed by Fisher stepwise discrimination, and its initial verification accuracy and leave-one-out cross-validation accuracy were 100% and 87.5%, respectively.

Ralstonia solanacearum Infection Disturbed the Microbiome Structure Throughout the Whole Tobacco Crop Niche as Well as the Nitrogen Metabolism in Soil.

Infections of Ralstonia solanacearum result in huge agricultural and economic losses. As known, the proposal of effective biological measures for the control of soil disease depends on the complex interactions between pathogens, soil microbiota and soil properties, which remains to be studied. Previous studies have shown that the phosphorus availability increased pathobiome abundance and infection of rhizosphere microbial networks by Ralstonia. Similarly, as a nutrient necessary for plant growth, nitrogen has also been suggested to be strongly associated with Ralstonia infection. To further reveal the relationship between soil nitrogen content, soil nitrogen metabolism and Ralstonia pathogens, we investigated the effects of R. solanacearum infection on the whole tobacco niche and its soil nitrogen metabolism. The results demonstrated that Ralstonia infection resulted in a reduction of the ammonium nitrogen in soil and the total nitrogen in plant. The microbes in rhizosphere and the plant's endophytes were also significantly disturbed by the infection. Rhodanobacter which is involved in nitrogen metabolism significantly decreased. Moreover, the load of microbial nitrogen metabolism genes in the rhizosphere soil significantly varied after the infection, resulting in a stronger denitrification process in the diseased soil. These results suggest that the application management strategies of nitrogen fertilizing and a balanced regulation of the rhizosphere and the endophytic microbes could be promising strategies in the biological control of soil-borne secondary disasters.

Bacterial Volatile-Mediated Suppression of Root-Knot Nematode (Meloidogyne incognita).

Root-knot nematodes (Meloidogyne spp.) are obligate plant parasites that cause severe economic losses to agricultural crops worldwide. Because of serious health and environmental concerns related to the use of chemical nematicides, the development of efficient alternatives is of great importance. Biological control through exploiting the potential of rhizosphere microorganisms is currently accepted as an important approach for pest management in sustainable agriculture. In our research, during screening of rhizosphere bacteria against the root-knot nematodes Meloidogyne incognita, Ochrobactrum pseudogrignonense strain NC1 from the rhizosphere of healthy tomatoes showed strong nematode inhibition. A volatile nematicidal assay showed that the cell-free fermentation filtrate in the first-row wells of 12-well tissue culture plates caused M. incognita juvenile mortality in the second-row wells. Gas chromatography-mass spectrometry analysis revealed that dimethyl disulfide (DMDS) and benzaldehyde were the main volatile compounds produced by strain NC1. The nematicidal activity of these compounds indicated that the lethal concentration 50 against the M. incognita juveniles in the second-row wells and the fourth-row wells were 23.4 µmol/ml and 30.7 µmol/ml for DMDS and 4.7 µmol/ml and 15.2 µmol/ml for benzaldehyde, respectively. A greenhouse trial using O. pseudogrignonense strain NC1 provided management efficiencies of root-knot nematodes of 88 to 100% compared with the untreated control. This study demonstrated that nematode-induced root-gall suppression mediated by the bacterial volatiles DMDS and benzaldehyde presents a new opportunity for root-knot nematode management.

Early combined rehabilitation intervention to improve the short-term prognosis of premature infants.

BACKGROUND: To explore the clinical effect of early combined rehabilitation intervention on premature infants in the neonatal intensive care unit (NICU). METHODS: Premature infants with gestational ages less than 32 weeks or birth weights less than 1500 g were included in the present study.The participants were divided into the intervention group and control group. All infants received the current routine treatment based on the clinical guidelines, and the intervention group was additionally treated by visual and auditory stimulation, oral motor function, respiratory function and neurodevelopmental training. The following clinical outcomes were compared: durations of oxygen supplementation and indwelling gastric tube use; incidences of retinopathy of prematurity (ROP) and neonatal necrotizing enterocolitis (NEC); Sliverman scores; incidences of bronchopulmonary dysplasia (BPD) and intraventricular haemorrhage; days of hospitalization; and neurodevelopmental outcomes. Datas were analysed using the following statistical tests: the chi-square test, the independent samples or paired t test, repeated measures ANOVA, and the Wilcoxon rank sum test. RESULTS: Compared with those in the control group, premature infants in the intervention group had shorter durations of oxygen supplementation and indwelling gastric tube use, fewer hospitalization days and lower incidences of ROP, BPD, and NEC.The intervention group had lower Sliverman scores and higher Ballard neuromuscular scores than the control group. CONCLUSION: Early combined rehabilitation intervention can improve the short-term clinical outcomes of premature infants.

Knockout of Dip2c in murine ES cell line IBMSe001-B-1 by CRISPR/Cas9 genome editing technology.

DIP2 protein contains three members: DIP2A, DIP2B and DIP2C, and are broadly expressed in the nervous system from Drosophila to human during embryonic development. Dip2c gene-associated mutations have been reported in tumors and neuronal diseases. However, the role ofDip2cin the context of mouse embryonic stem (mES) cells has not been explored.To investigate the biological function of Dip2c during early embryo development, we generated Dip2c-/- mES line using a CRISPR/Cas9 system. This cell line has contributed to further investigation of molecular mechanism of Dip2c during cell differentiation, as well as a cell model for screening for neurogenic drug and cancer clinical cure.

SLC12A8 plays a key role in bladder cancer progression and EMT.

Bladder cancer is the most common malignant tumor of the urinary system. The intention of the present research is to explore the prognostic value and biological function of solute carrier family 12 member 8 (SLC12A8) in bladder cancer. The analysis based on the TCGA and ONCOMINE database revealed that the expression of SLC12A8 in bladder cancer was notably increased compared with the normal group. SLC12A8 expression was notably correlated with the age, pathological stage, T-stage, and lymph node metastasis of bladder cancer patients. Moreover, the patients' overall survival was notably shorter in the high SLC12A8 group. Compared with the control, SLC12A8 upregulation enhanced the proliferative, invasive, and migratory capacities of bladder cancer cells and promoted the expression of epithelial-mesenchymal transition (EMT) protein markers including ß-catenin, vimentin, snail, and slug, while reduced the expression of E-cadherin. In the case of downregulated SLC12A8 expression, the proliferative, invasive, and migratory capacities of bladder cancer cells and the expression of EMT protein markers presented the opposite trend. This study demonstrated that SLC12A8 was highly correlated with oncogenesis and progression of bladder cancer, indicating that SLC12A8 may be a meaningful biomarker for initial diagnosis and early treatment of bladder cancer.

Time Delay Complex Chen Chaotic System and Secure Communication Scheme for Wireless Body Area Networks.

Although many chaotic systems with time delays have been studied in recent years, most studies have only focused on the theoretical level, without special applications. Therefore, we present a basic introduction of a time delay complex Chen chaotic system, including the influence of parameter changes and time delay factors on the time delay system. On the basis of complex modified projection synchronization (CMPS), we detail the design of a new controller and communication scheme and apply this communication scheme to a wireless body area network (WBAN), in order to encrypt and decrypt body data collected by sensors. Finally, we perform a numerical simulation, demonstrating the effectiveness of the proposed communication scheme.

EZH2 overexpression dampens tumor-suppressive signals via an EGR1 silencer to drive breast tumorigenesis.

The mechanism underlying EZH2 overexpression in breast cancer and its involvement in tumorigenesis remain poorly understood. In this study, we developed an approach to systematically identify the trans-acting factors regulating the EZH2 expression, and identified more than 20 such factors. We revealed reciprocal regulation of early growth response 1 (EGR1) and EZH2: EGR1 activates the expression of EZH2, and EZH2 represses EGR1 expression. Using CRISPR-mediated genome/epigenome editing, we demonstrated that EHZ2 represses EGR1 expression through a silencer downstream of the EGR1 gene. Deletion of the EGR1 silencer resulted in reduced cell growth, invasion, tumorigenicity of breast cancer cells, and extensive changes in gene expression, such as upregulation of GADD45, DDIT3, and RND1; and downregulation of genes encoding cholesterol biosynthesis pathway enzymes. We hypothesize that EZH2/PRC2 acts as a "brake" for EGR1 expression by targeting the EGR1 silencer, and EZH2 overexpression dampens tumor-suppressive signals mediated by EGR1 to drive breast tumorigenesis.

Time-course relationship between environmental factors and microbial diversity in tobacco soil.

Soil physicochemical properties and microbial diversity both play equally important roles in tobacco cultivation. However, the relationship between these factors remains unclear. In this study, we investigated their correlations through the whole tobacco growth period, including the pretransplanting (YX-p), root extending (R), flourishing (F), and mature (M) stages in the Yuxi region of the Yunnan-Guizhou Plateau by measuring physicochemical properties and conducting 16S/18S rRNA analysis. The analysis demonstrated that the microbial community richness and diversity continuously changed along with the growth course of the tobacco. Multiple environmental factors showed a certain correlation with the diversity of microbial communities. Some bacteria could accumulate nitrogen during the growth stages, and the diversity of the bacterial community also increased when the content of organic matter rose. In addition, the water content and available K also influenced the diversity of the microbial community. The dynamic changes in soil physicochemical properties and enzyme activities gave rise to differences in the microbial community composition and structure, all of which affected the growth of tobacco. This study revealed the time-course relationship between environmental factors and microbial diversity in tobacco soil. An understanding of this relationship provides guidance for research on the interaction system of plants, soil and microbes and on improving plant yield and quality.

Refractive index sensor based on multiple Fano resonances in a plasmonic MIM structure.

A chip-scale refractive index sensor based on multiple Fano resonances is proposed by using a metal-insulator-metal (MIM) structure, which is constructed by two side-coupled semi-ring cavities and a vertical cavity. The finite-difference time-domain method and multimode interference coupled-mode theory are employed to simulate and analyze the transmission spectra of this structure, respectively. First, dual Fano resonances are generated in the MIM structure with a baffle and a semi-ring cavity. By arranging two additional cavities, the mode interferences successfully induce up to six ultra-sharp and asymmetrical Fano peaks. The calculated sensing performances are available with ultra-high sensitivity of 1405 nm/RIU and figure of merit of 3.62×105. This chip-scale refractive index sensor may have great applications in highly integrated photonic circuits.

Four-week administration of nicotinemoderately impacts blood metabolic profile and gut microbiota in a diet-dependent manner.

As the primary active component in tobacco, nicotine affects many aspects of human metabolism. Diet and gut microbiota are key factors that profoundly influence human lipid and glucose metabolism. However, the diet-based differential impacts of nicotine on blood lipid and glucose levels as well as on the gut microbiota are still largely unknown. Here we show that 4-week oral administration of nicotine (2 mg/kg) resulted in bodyweight and fat decrease in both normal-chow (NCD)- and high-fat diet (HFD)-fed mice. But nicotine showed little influence on the plasma levels of lipids, glucose and inflammatory cytokines in NCD-fed mice but moderately deteriorated these parameters in HFD-fed ones. 16S sequencing showed that nicotine perturbed bacterial diversity and community composition of gut microbiota more pronouncedly in HFD mice. At genus level, nicotine dramatically increased Ruminococcaceae UCG-009 in HFD condition but not in NCD feeding. Interestingly, co-treatment with antibiotics (ampicillin + norfloxacin) substantially abolished the lipid-enhancing effect of nicotine in HFD-fed mice, suggesting an important role of gut microbes in the lipid-modulatory effect of nicotine. Together, our results indicate that the harmful effects of nicotine on metabolism and systemic inflammation are diet-dependent. Chronic exposure to nicotine may alter the gut microbiota especially in HFD-fed animals.

Plasmonic-induced absorption based on an end-coupled combined resonance system of a semiannular cavity and rectangular cavity.

A semiannular rectangular composite cavity structure based on metal-insulator-metal waveguides is proposed. By adding a rectangular cavity at a suitable position around the semiannular cavity (SAC), a single analogous plasmonic-induced absorption (PIA) effect is achieved at the expected mode of the SAC structure. After adding two rectangular cavities together in the SAC system, dual analogous PIA effects for both modes can be realized simultaneously. In addition, the phase response is also studied, and abnormal dispersions are achieved in the PIA windows, which can be used in the integrated optics for fast/slow light. The performances of the proposed two-dimensional structure are analyzed and studied by the coupled-mode theory and the finite-difference time-domain method, respectively.

Preparation of Ni based mesoporous Al2O3 catalyst with enhanced CO2 methanation performance.

A Ni based mesoporous γ-Al2O3 (MA) catalyst was prepared via partial hydrolysis without organic surfactants and employed in the carbon dioxide methanation reaction. The obtained catalysts were characterized by N2 adsorption-desorption, H2-TPR, XRD, XPS, TG, SEM and TEM-EDS techniques. CO2 methanation was performed in a fixed-bed reactor. A high surface area of MA with excellent hydrothermal stability was obtained, which promoted the dispersion of nickel species, producing a better catalytic performance. Incorporation of more NiO species into the Ni/MA catalyst increased the amount of active metallic Ni sties, further improving the catalytic activity and CH4 selectivity. Moreover, the monolithic skeleton of MA with fabric-like walls suppressed the aggregation of active metallic Ni sites and carbon deposition, enhancing the catalyst's stability, which provides a new insight for potential industrial applications.