The relationship of immune cells with autism spectrum disorder: a bidirectional Mendelian randomization study.

BACKGROUND: Observational studies have indicated a correlation between immunological inflammation and the risk of autism spectrum disorder (ASD). However, the causal relationship between immunological inflammation and ASD remains uncertain. METHODS: Immunity-wide data sources were retrieved from the GWAS catalog. Genetic summary data on ASD were retrieved from two independent GWAS. We performed two independent bi-directional, two-sample Mendelian randomization (MR) analyses and a meta-analysis based on the two independent MR estimates to assess the causal relationship between ASD and immune cell signatures. RESULTS: We have discovered 26 potential correlations between genetic predisposition in the immunophenotypes and ASD. The meta-analysis of the two inverse variance weighted (IVW)-produced estimates provided further evidence supporting the potential causal relationship between immunophenotypes and ASD. Based on the findings of the reverse MR analysis, it was determined that there are two potential negative causal relationships between ASD and immunophenotypes. However, the meta-analysis of the two IVW-derived MR estimates indicated that immunophenotypes were not significantly influenced by ASD (OR = 0.87, 95% CI = 0.73 -1.03, P = 0.09; OR = 0.91, 95% CI = 0.81-1.01, P = 0.08). CONCLUSIONS: This study expanded immune cell subtypes that were potentially causally associated with ASD risk as well as identified ASD-specific immune cell subtypes. The discovery has the potential to lead to earlier detection and more effective treatment techniques.

Perinatal Transmission of 2019 Coronavirus Disease-Associated Severe Acute Respiratory Syndrome Coronavirus 2: Should We Worry?

We present 2 cases of coronavirus disease 2019 (COVID-19)-associated severe respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during the third trimester of pregnancy. Both mothers and newborns had excellent outcomes. We failed to identify SARS-CoV-2 in all of the products of conception and the newborns. This report provided evidence of low risk of intrauterine infection by vertical transmission of SARS-CoV-2.

Association between breastfeeding and Kawasaki disease: a case-control study.

The association between breastfeeding and Kawasaki disease is not fully understood. We performed a case-control study to examine the association between breastfeeding and Kawasaki disease. In this study, 389 children diagnosed with Kawasaki disease and 426 gender- and age-matched controls were identified at Renmin Hospital of Wuhan University between November 2013 and March 2019. Demographic and clinical data were collected from a structured telephone interview and medical record database. Odds ratio and 95% confidence interval for risk of Kawasaki disease were estimated. Children who were breastfed exclusively had a decrease in developing Kawasaki disease (adjusted odds ratios and 95% confidence intervals 0.53 (0.38-0.74). Although the risk reduction was not statistically different, partial breastfeeding also provided a protective effect (adjusted odds ratios and 95% confidence intervals 0.70 (0.48-1.01). In the stratified analysis, we still observed that exclusive breastfeeding was inversely associated with the development of complete Kawasaki disease (adjusted odds ratios and 95% confidence intervals 0.52 (0.31-0.88) and incomplete Kawasaki disease (adjusted odds ratios and 95% confidence intervals 0.54 (0.38-0.77). However, there was no significant association between exclusive breastfeeding and the intravenous immunoglobulin treatment response (adjusted odds ratios and 95% confidence intervals 0.69 (0.27-1.69) and the risk of coronary artery lesions (adjusted odds ratios and 95% confidence intervals 0.79 (0.49-1.31) in Kawasaki disease.Conclusion: Our analysis suggests that exclusive breastfeeding was inversely associated with the development of Kawasaki disease and that breastfeeding might be a potential protective factor against Kawasaki diseaseWhat is known• Previous studies have demonstrated that breastfeeding has been shown to potentially confer protection against several autoimmune disorders of childhood.• The association between breastfeeding and Kawasaki disease is not fully understood.What is newThe first study to evaluate the association between breastfeeding and the development of Kawasaki disease in China with a large sample size.• Exclusive breastfeeding was inversely associated with the development of Kawasaki disease and breastfeeding might be a potential protective factor against Kawasaki disease.

Construction of prognostic risk prediction model based on high-throughput sequencing expression profile data in childhood acute myeloid leukemia.

This study aimed to identify critical prognostic molecular markers in Childhood acute myeloid leukemia (AML) and construct nomogram-based model for prognostic prediction. The RNA-sequencing profiles and corresponding clinical information were downloaded from TCGA database. Differential expressed genes (DEG) were screened using limma package, subsequently following by GO and KEGG pathway analysis. Univariate and multivariate cox regression analysis were performed to screen critical DEGs. Nomogram-based prediction model were constructed to identify clinical factors with independent prognostic values, and the accuracy of this model was validated. A total of 214 DEGs were identified from relapse AML samples compared with non-relapse samples. These DEGs were mainly involved in twenty GO terms and three signaling pathways, such as chromatin assembly or disassembly, cytokine-cytokine receptor interaction, and JAK-STAT signaling pathway. Among these genes, Univariate and multivariate cox regression analysis results showed that relapse and risk score were significantly correlated with survival outcomes. Finally, the accuracy ability of nomogram-based prediction model was validated. These six DEGs (ABCA5, CYP7A1, HERC5, etc.) play major roles in AMLs progression. Our nomogram-based prognostic predictive model might be an effective method to estimate survival probability of AML patients with different risk status.

Effects of low-frequency repetitive transcranial magnetic stimulation on depression- and anxiety-like behaviors in epileptic rats.

Low-frequency repetitive transcranial magnetic stimulation (rTMS) has been considered as a treatment option for depression and anxiety. However, its role in epilepsy comorbid with depression and anxiety is unclear. Therefore, we evaluated whether low-frequency rTMS can alleviate depression- and anxiety-like behavior in epileptic rats. Forty-eight adult rats were allocated at random to four groups: Control, Pentylenetetrazol (PTZ), PTZ-rTMS and PTZ-Sham. The control group received intraperitoneal injections of normal saline, while the other groups received intraperitoneal injections of pentylenetetrazol (35 mg/kg/d) once a day for 15 days. Low-frequency rTMS or sham stimulation were administered to the PTZ-rTMS and PTZ-Sham group, respectively, over the two-week period. The open-field test (OFT), elevated plus-maze test (EPM) and forced swimming test (FST) were carried out before the experiment, on the 8th and 15th day to assess depression- and anxiety-like behavior in the rats. Two weeks of low-frequency rTMS treatment could not impair the increases of seizure severity in epileptic rats. However, relative to the PTZ and PTZ-Sham group, the two-week low-frequency rTMS treatment significantly reduced the immobility time in the forced swimming test and attenuated the progressive decrease in total distance traveled, frequency of rearing, velocity in the open-field test, number of entries in the open arms (%) and the time spent in the open arms (%) in the elevated plus-maze test of the PTZ-rTMS group. We proposed that low-frequency rTMS can benefit epileptic rats via amelioration of comorbid depression and anxiety, but it can not alleviate the seizure severity.

Upconversion luminescence resonance energy transfer-based aptasensor for the sensitive detection of oxytetracycline.

In this work, a biosensor based on luminescence resonance energy transfer (LRET) from NaYF4:Yb,Tm upconversion nanoparticles (UCNPs) to SYBR Green I has been developed. The aptamers are covalently linked to UCNPs and hybridized with their complementary strands. The subsequent addition of SYBR Green allows SYBR Green I to insert into the formed double-stranded DNA (dsDNA) duplex and brings the energy donor and acceptor into close proximity, leading to the fluorescence of UCNPs transferred to SYBR Green I. When excited at 980 nm, the UCNPs emit luminescence at 477 nm, and this energy is transferred to SYBR Green I, which emits luminescence at 530 nm. In the presence of oxytetracycline (OTC), the aptamers prefer to bind to its corresponding analyte and dehybridize with the complementary DNA. This dehybridization leads to the liberation of SYBR Green I, which distances SYBR Green I from the UCNPs and recovers the UCNPs' luminescence. Under optimal conditions, a linear calibration is obtained between the ratio of I530 to I477 nm (I530/I477) and the OTC concentration, which ranges from 0.1 to 10 ng/ml with a limit of detection (LOD) of 0.054 ng/ml.

Simultaneous aptasensor for multiplex pathogenic bacteria detection based on multicolor upconversion nanoparticles labels.

A highly sensitive and specific multiplex method for the simultaneous detection of three pathogenic bacteria was fabricated using multicolor upconversion nanoparticles (UCNPs) as luminescence labels coupled with aptamers as the molecular recognition elements. Multicolor UCNPs were synthesized via doping with various rare-earth ions to obtain well-separated emission peaks. The aptamer sequences were selected using the systematic evolution of ligands by exponential enrichment (SELEX) strategy for Staphylococcus aureus, Vibrio parahemolyticus, and Salmonella typhimurium. When applied in this method, aptamers can be used for the specific recognition of the bacteria from complex mixtures, including those found in real food matrixes. Aptamers and multicolor UCNPs were employed to selectively capture and simultaneously quantify the three target bacteria on the basis of the independent peaks. Under optimal conditions, the correlation between the concentration of three bacteria and the luminescence signal was found to be linear from 50-10(6) cfu mL(-1). Improved by the magnetic separation and concentration effect of Fe3O4 magnetic nanoparticles, the limits of detection of the developed method were found to be 25, 10, and 15 cfu mL(-1) for S. aureus, V. parahemolyticus, and S. typhimurium, respectively. The capability of the bioassay in real food samples was also investigated, and the results were consistent with experimental results obtained from plate-counting methods. This proposed method for the detection of various pathogenic bacteria based on multicolor UCNPs has great potential in the application of food safety and multiplex nanosensors.

An Interval Prediction of Chloroprene Rubber Crack Propagation Characteristics Based on Thermal Accelerated Aging.

Thermo-oxidative aging plays an important role in changing the properties of rubber materials; it significantly decreases the fatigue life of air spring bags and further causes safety hazards. However, due to the great uncertainty of rubber material properties, an effective interval prediction model has not been established considering the effect of aging on airbag rubber properties. To solve the problem, this study proposes an interval parameter correlation model that can more accurately describe rubber crack propagation characteristics by considering material uncertainty. Furthermore, an aging prediction model of the rubber crack propagation characteristic region is established based on the Arrhenius equation. The effectiveness and accuracy of the method are verified by comparing the test and prediction results under the temperature spectrum. The method can be used to determine the variations in the interval change of the fatigue crack propagation parameters during rubber aging and can guide fatigue reliability analyses of air spring bags.

Neuroinflammatory Biomarkers in the Brain, Cerebrospinal Fluid, and Blood After Ischemic Stroke.

The most frequent type of stroke, known as ischemic stroke (IS), is a significant global public health issue. The pathological process of IS and post-IS episodes has not yet been fully explored, but neuroinflammation has been identified as one of the key processes. Biomarkers are objective indicators used to assess normal or pathological processes, evaluate responses to treatment, and predict outcomes, and some biomarkers can also be used as therapeutic targets. After IS, various molecules are produced by different cell types, such as microglia, astrocytes, infiltrating leukocytes, endothelial cells, and damaged neurons, that participate in the neuroinflammatory response within the ischemic brain region. These molecules may either promote or inhibit neuroinflammation and may be released into extracellular spaces, including cerebrospinal fluid (CSF) and blood, due to reasons such as BBB damage. These neuroinflammatory molecules should be valued as biomarkers to monitor whether their expression levels in the blood, CSF, and brain correlate with the diagnosis and prognosis of IS patients or whether they have potential as therapeutic targets. In addition, although some molecules do not directly participate in the process of neuroinflammation, they have been reported to have potential diagnostic or therapeutic value against post-IS neuroinflammation, and these molecules will also be listed. In this review, we summarize the neuroinflammatory biomarkers in the brain, CSF, and blood after an IS episode and the potential value of these biomarkers for the diagnosis, treatment, and prognosis of IS patients.

Ultrasensitive electrochemical analysis of two analytes by using an autonomous DNA machine that works in a two-cycle mode.

We report a novel autonomous DNA machine for amplified electrochemical analysis of two DNAs. The DNA machine operates in a two-cycle working mode to amplify DNA recognition events; the working mode is assisted by two different nicking endonucleases (NEases). Two bio-barcode probes, a ZnS nanoparticle (NP)-DNA probe and a CdS NP-DNA probe, were used to trace two target DNAs. The detection system was based on a sensitive differential pulse anodic stripping voltammetry (DPASV) method for the simultaneous detection of Zn(II) and Cd(II) tracers, which were obtained by dissolving the two probes. Under the optimised conditions, detection limits as low as 5.6×10(-17) (3σ) and 4.1×10(-17) M (3σ) for the two target DNAs were achieved. It has been proven that the DNA machine system can simultaneously amplify two target DNAs by more than four orders of magnitude within 30 min at room temperature. In addition, in combination with an aptamer recognition strategy, the DNA machine was further used in the aptamer-based amplification analysis of adenosine triphosphate (ATP) and lysozyme. With the amplification of the DNA machine, detection limits as low as 5.6×10(-9) M (3σ) for ATP and 5.2×10(-13) M (3σ) for lysozyme were simultaneously obtained. The satisfactory determination of ATP and lysozyme in Ramos cells reveals the good selectivity and feasibility of this protocol. The DNA machine is a promising tool for ultrasensitive and simultaneous multianalysis because of its remarkable signal amplification and simple machine-like operation.

Long noncoding RNA expression profiling identifies MIR210HG as a novel molecule in severe preeclampsia.

OBJECTIVE: Preeclampsia (PE) is a potentially fatal pregnancy-specific complication. Nevertheless, the pathogenesis of PE remains indistinct. Recently, increasing studies emphasized that long noncoding RNAs (lncRNAs) functions as imperative regulators in PE. The aim of this study was to compare the lncRNAs transcript profile of placentae in early onset severe preeclampsia (EOSP) with lncRNAs in normal pregnancy (NP) and to evaluate the role of lncRNA MIR210HG (microRNA 210 host gene) in the PE pathogenesis. METHODS: Using RNA sequencing, we compared transcriptome profiles of placentae in EOSP (n = 3) and NP (n = 3). Bioinformatic tools were used to predict the function of differentially expressed genes while qRT-PCR was used to verify RNA sequencing data. The role of MIR210HG in HTR8/SVneo migration and invasion were analyzed by in vitro MIR210HG gene overexpression. RESULTS: Our results showed that 527 lncRNAs and 600 mRNAs were differentially expressed in placental samples of EOSP, and the analysis identified 63 key EOSP related genes. As indicated by bioinformatics analyses, lncRNA MIR210HG was a potential pathogenic marker of PE. LncRNA-MIR210HG expression was upregulated in placental samples of PE and enriched in the canonical Wnt signalling pathway. MiR210HG overexpression inhibited HTR8/SVneo cell migration and invasion in vitro. Additionally, miR210HG upregulated dickkopf-1 expression via the sponging of microRNA-520a-3p (miR-520a-3p), thus repressing trophoblast migration and invasion. CONCLUSION: Our study showed that MiR210HG is a novel upregulated lncRNA in the placentas of PE and MiR210HG regulates the migration and invasive potential of HTR-8/SVneo cell by targeting the miR-520a-3p/Dickkopf-1 axis.

An autonomous bio-barcode DNA machine for exponential DNA amplification and its application to the electrochemical determination of adenosine triphosphate.

A novel autonomous bio-barcode DNA machine that is driven by template-dependent DNA replication is developed to exponentially amplify special DNA sequences. Combined with a DNA aptamer recognition element, the DNA machine can be further applied in the aptamer-based, amplified analysis of small molecules. As a model analyte, adenosine triphosphate (ATP) is determined by using the DNA machine system in combination with a DNA aptamer recognition strategy and differential pulse anodic stripping voltammetry (DPASV). Under the optimum conditions, detection limits as low as 2.8×10(-17) M (3σ) for target DNA and 4.7×10(-9) M (3σ) for ATP are achieved. The satisfactory determination of ATP in K562 leukemia cell and Ramos Burkitt's lymphoma cell reveal that this protocol possesses good selectivity and practicality. As a promising biomolecular device, this DNA machine may have an even broader application in the rapidly developing field of nanobiotechnology.

Cognition Deficits in Parkinson's Disease: Mechanisms and Treatment.

Parkinson's disease (PD) is the second most common progressive neurodegenerative disorder mainly in middle-elderly population, which represents diverse nonmotor symptoms (NMS) besides such well-documented motor symptoms as bradykinesia, resting tremor, rigidity, and postural instability. With the advancement of aging trend worldwide, the global prevalence of PD is mounting up year after year. Nowadays, accumulating lines of studies have given a comprehensive and thorough coverage of motor symptoms in PD. Yet much less attention as compared has been paid to the nonmotor symptoms of PD, such as cognition deficits. Of note, a patient with PD who suffers from cognitive impairment may harbour a statistically significantly higher risk of progressing toward dementia, which negatively affects their life expectancy and daily functioning and overall lowers the global quality of life. Furthermore, it is a widely held view that cognitive dysfunction does not just occur in the late stage of PD. On the basis of numerous studies, mild cognitive impairment (MCI) is a harbinger of dementia in PD, which is observed as an intermediate state with considerable variability; some patients remain stable and some even revert to normal cognition. Considered that the timing, profile, and rate of cognitive impairment vary greatly among PD individuals, it is extremely urgent for researchers and clinicians alike to identify and predict future cognitive decline in this population. Simultaneously, early screening and canonical management of PD with cognitive deficits are very imperative to postpone the disease progression and improve the prognosis of patients. In our review, we focus on a description of cognitive decline in PD, expound emphatically the pathological mechanisms underlying cognition deficits in PD, then give a comprehensive overview of specific therapeutic strategies, and finally dissect what fresh insights may bring new exciting prospect for the subfield.

The Protective Effect of Breastfeeding on Febrile Seizures: A Case-Control Study.

Objective: Our study was performed to analyze the interrelationship between breastfeeding for the first 6 months of life and the incidence of febrile seizures (FS). Study Design: A case-control study was conducted in Renmin Hospital of Wuhan University. Three hundred thirty-six patients diagnosed with FS were enrolled as the case group, and 336 febrile children with matched age and gender were enrolled as the control group. Clinical information of all cases was collected from the Electronic Medical Record, including feeding patterns. The primary outcome was the difference of feeding modes between cases and controls, while the secondary outcome included the difference of feeding patterns between simple FS (SFS) and complex FS (CFS). Results: The 336 patients with FS comprised 294 with SFS and 42 with CFS. The difference in feeding methods between the case group and the control group was statistically significant, and children who were breastfed exclusively had a lower risk of suffering from FS compared with formula feeding (odds ratio [OR], 0.504 and 95% confidence interval [CI], 0.303-0.841); although partial breastfeeding exhibited a slight protective effect against FS, the protective role was not statistically significant (OR, 1.016 and 95% CI, 0.560-1.846). In addition, our dates showed that feeding mode was not a risk factor in the occurrence of SFS or CFS (p > 0.05). Conclusion: Our data confirm that exclusive breastfeeding is an independent protective factor that can reduce the occurrence of FS.

Association between depression and the subsequent risk of Parkinson's disease: A meta-analysis.

BACKGROUND: Observational studies, including recent large cohort studies, have reported an association between depression and the risk of Parkinson's disease (PD); however, conclusions were inconsistent. Clarifying this relation might improve the understanding of risk factors for and the disease mechanisms in PD. Therefore, we performed a meta-analysis to examine whether depression is associated with an increased risk of PD. METHODS: A literature search in the PubMed, EMBASE, Scopus, PsycINFO and Web of Science databases was undertaken through March 2018, looking for observational studies evaluating the association between depression and the risk of PD. Pooled relative risk (RR) estimates and 95% confidence intervals (CIs) were calculated using a random-effects model. Subgroup analyses and sensitivity analyses were also performed. RESULTS: A random-effects meta-analysis of 5 cohort studies and 6 case-control studies demonstrated a significant positive association between depression and a subsequent risk of PD (RR, 2.20; 95% CI, 1.87-2.58), and it was consistent across subgroups. Furthermore, sensitivity analysis confirmed the stability of the results; visual examination of funnel plots and Begg's and Egger's tests showed no evidence of publication bias. CONCLUSIONS: Our meta-analysis demonstrated that persons with depression exhibited an increased risk of a subsequent PD diagnosis. The pathophysiological and psychological mechanisms underlying this association are still unclear and warrant further research.

The Interrelation between Reactive Oxygen Species and Autophagy in Neurological Disorders.

Neurological function deficits due to cerebral ischemia or neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD) have long been considered a thorny issue in clinical treatment. Recovery after neurologic impairment is fairly limited, which poses a major threat to health and quality of life. Accumulating evidences support that ROS and autophagy are both implicated in the onset and development of neurological disorders. Notably, oxidative stress triggered by excess of ROS not only puts the brain in a vulnerable state but also enhances the virulence of other pathogenic factors, just like mitochondrial dysfunction, which is described as the culprit of nerve cell damage. Nevertheless, autophagy is proposed as a subtle cellular defense mode against destructive stimulus by timely removal of damaged and cytotoxic substance. Emerging evidence suggests that the interplay of ROS and autophagy may establish a determinant role in the modulation of neuronal homeostasis. However, the underlying regulatory mechanisms are still largely unexplored. This review sets out to afford an overview of the crosstalk between ROS and autophagy and discusses relevant molecular mechanisms in cerebral ischemia, AD, and PD, so as to provide new insights into promising therapeutic targets for the abovementioned neurological conditions.

Genetic deletion of Rnd3 in neural stem cells promotes proliferation via upregulation of Notch signaling.

Rnd3, a Rho GTPase, is involved in the inhibition of actin cytoskeleton dynamics through the Rho kinase-dependent signaling pathway. We previously demonstrated that mice with genetic deletion of Rnd3 developed a markedly larger brain compared with wild-type mice. Here, we demonstrate that Rnd3 knockout mice developed an enlarged subventricular zone, and we identify a novel role for Rnd3 as an inhibitor of Notch signaling in neural stem cells. Rnd3 deficiency, both in vivo and in vitro, resulted in increased levels of Notch intracellular domain protein. This led to enhanced Notch signaling and promotion of aberrant neural stem cell growth, thereby resulting in a larger subventricular zone and a markedly larger brain. Inhibition of Notch activity abrogated this aberrant neural stem cell growth.

Formulation of intumescent flame retardant coatings containing natural-based tea saponin.

Natural product tea saponin (TS), extracted from the nutshell of camellia (Camellia oleifera Abel, Theaceae), was introduced into intumescent flame retardant formulations as blowing agent and carbon source. The formulations of the flame retardant system were optimized to get the optimum proportion of TS, and intumescent flame retardant coatings containing tea saponin (TS-IFRCs) were then prepared. It was found that TS can significantly affect the combustion behavior and the thermal stability of TS-IFRCs evaluated by cone calorimetry and simultaneous thermal analyzer, respectively. It was shown that TS, degraded to water vapor and carbon at high temperatures, can combine with other components to form a well-developed char layer. The char layer was supposed to inhibit erosion upon exposure to heat and oxygen and enhance the flame retardancy of TS-IFRCs. In addition, the smoke release of TS-IFRCs was also studied, which provided a low amount of smoke production.

Dual fluorescence resonance energy transfer assay between tunable upconversion nanoparticles and controlled gold nanoparticles for the simultaneous detection of Pb²âº and Hg²âº.

In this work, we presented a novel dual fluorescence resonance energy transfer (FRET) system for the simultaneous detection of Pb(2+) and Hg(2+). This system employed two color upconversion nanoparticles (UCNPs) as the donors, and controlled gold nanoparticles (AuNPs) as the acceptors. The two donor-acceptor pairs were fabricated by hybridizing the aptamers and their corresponding complementary DNA. Thus, the green and red upconversion fluorescence could be quenched because of a good overlap between the UCNPs fluorescence emission and the AuNPs absorption spectrum. In the presence of Pb(2+) and Hg(2+), the aptamers preferred to bind to their corresponding analytes and formed a G-quadruplexes structure for Pb(2+) and the hairpin-like structure for Hg(2+). As a result, the dual FRET was disrupted, and the green and red upconversion fluorescence was restored. Under optimized experimental conditions, the relative fluorescence intensity increased as the metal ion concentrations were increased, allowing for the quantification of Pb(2+) and Hg(2+). The relationships between the fluorescence intensity and plotting logarithms of ion concentrations were linear in the range from 0.1 to 100 nM for Pb(2+) and 0.5 to 500 nM for Hg(2+), and the detection limits of Pb(2+) and Hg(2+) were 50 pM and 150 pM, respectively. As a practical application, the aptasensor was used to monitor Pb(2+) and Hg(2+) levels in naturally contaminated samples and human serum samples. Ultimately, this type of dual FRET could be used to detect other metal ions or contaminants in food safety analysis and environment monitoring.