Influence of samarium modification on the phase-change performance and phase structure of tin antimonide.

This work presents the optimization of the crystallization behavior and reliability of Sn15Sb85thin films by doping Sm element. The phase transition behaviors induced by thermal were investigated byin situresistance measurement. With the addition of Sm element, Sn15Sb85film exhibits the superior crystallization temperature (232 °C) and data conservation (172.32 °C for 10 years), larger activation energy of crystallization (4.91 eV) and crystalline resistance (∼103Ω), which contributes to the increased thermal stability of the amorphous state and decrease in the programming energy. The Sm-doping can broaden the energy band gap from 0.55 to 1.07 eV. The amorphous Sm and Sn compositions could retard grain growth and refine grain size from 21.13 to 11.13 nm, combining with x-ray diffraction and x-ray photoelectron spectroscopy. The surface morphology of Sn15Sb85film becomes smoother after Sm doping as determined by atomic force microscopy images, resulting in the improved interfacial reliability. Phase change memory devices based on Sm0.095(Sn15Sb85)0.905films can successfully achieve the complete SET and RESET reversible operation process with high operating speed (200 ns) and low power consumption (1.6 × 10-10J). The results suggest that doping the proper concentration of Sm element will be an effectual solution to adapt and optimize the crystallization properties of Sn15Sb85phase change material.

Simultaneously achieving high performance of thermal stability and power consumption via doping yttrium in Sn15Sb85thin film.

The effects of yttrium dopants on the phase change behavior and microstructure of Sn15Sb85films have been systematically investigated. The yttrium-doped Sn15Sb85film has the higher phase transition temperature, ten year data retention ability and crystallization activation energy, which represent a great improvement in thermal stability and data retention. X-ray diffraction, transmission electron microscopy and x-ray photoelectron spectroscopy reveal that the amorphous Sn and Y components restrict the grain growth and decrease the grain size. Raman mode typically associated with Sb is altered when the substance crystallized. Atomic force microscopy results show that the surface morphology of the doped films becomes smoother. T-shaped phase change storage cells based on yttrium-doped Sn15Sb85films exhibit the lower power consumption. The results demonstrate that the crystallization characteristics of Sn15Sb85film can be tuned and optimized through the yttrium dopant for the excellent performances of phase change memory.

The Complete Genome Sequence Resource of Rhizospheric Soil-Derived Bacillus velezensis Yao, with Biocontrol Potential Against Fusarium solani-Induced Pepper Root Rot.

The pepper rhizospheric soil-derived Bacillus velezensis Yao from the Shangqiu region of the Henan province in China possesses antagonistic activity against Fusarium solani, which causes pepper root rot. In this report, we introduced the entire genomic sequence of B. velezensis Yao, which is 3,951,864 bp long, with 46.61% G+C content, and 4,097 genes. Using antiSMASH analysis, we predicted 12 gene clusters that encode for secondary antimicrobial metabolites and multiple genes that regulate plant bacterial interactions. The B. velezensis Yao genome data may be a valuable resource as this strain may serve as an effective biocontrol agent against pepper root rot.

Autoantibodies Targeting Unknown Epitope Autoimmune Encephalitis and the Effect of Modified Electroconvulsive Therapy: Report of Three Cases.

Objective: Generally autoimmune encephalitis (AE) cases present with central nervous system symptoms. Many types of autoantibodies are associated with autoimmune encephalitis, with anti-N-methyl-D-aspartate receptor being the most commonly reported. However, autoimmune encephalitis cases with autoantibodies targeting unknown epitopes are increasingly recognized. This article aims to summarize the clinical experience and assess the feasibility of modified electroconvulsive therapy (MECT) as an adjunctive treatment method for autoimmune encephalitis patients with poor response to first-line immunotherapy and mainly displaying psychiatric symptoms. Methods: This work reports three cases of which two have been diagnosed as autoantibodies targeting unknown epitope autoimmune encephalitis while one has been diagnosed as anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis and all were effectively treated with MECT. Results: All three cases that otherwise failed to respond to standard immunotherapy for controlling psychiatric symptoms exhibited excellent clinical outcomes following MECT. The underlying mechanism of action of MECT is unclear and whether such an effect involves a neurotransmitter rebalance in the brain remains uncertain. At present, we have observed only a small number of clinical cases, warranting further research among a larger number of clinical cases and more systematic multicenter retrospective analysis. Conclusions: It should be noted that, while our experience supports the utility of MECT in the treatment of certain cases of AE, this option should be regarded as an adjuvant therapy after standard immunosuppressive therapy. Clinicians must be aware that patients should be provided with psychiatric or neurological services for timely diagnosis along with timely and appropriate treatment.

Efficacy and safety comparison between R-CHOP and modified NHL-BFM-90 regimens in children and adolescents with diffuse large B-cell lymphoma.

Studies comparing the efficacy and safety of R-CHOP and modified non-Hodgkin lymphoma Berlin-Frankfurt-Münster-90 (NHL-BFM-90) regimens in children and adolescents with diffuse large B-cell lymphoma (DLBCL) are lacking. Thus, we retrospectively analyzed 85 DLBCL patients aged ≤18 years from 2000 to 2020; 74 patients received the modified NHL-BFM-90 regimen, and 11 received the R-CHOP regimen. The 5-year OS and event-free survival (EFS) rates between the modified NHL-BFM-90 and R-CHOP regimens were 91.0% vs. 90.9% (P = 0.466) and 89.8% vs. 68.6% (P = 0.055), respectively. In the stratified analysis, the survival outcome of pediatric patients treated with the modified NHL-BFM-90 regimen was not significantly different from that of adolescent patients. The OS and EFS rates of patients with early-stage disease were both 100%. Patients in the advanced-stage group who were treated with the modified NHL-BFM-90 regimen had superior EFS rates (P < 0.05). The frequency of severe adverse events from the two regimens was similar. There were no treatment-related deaths. We concluded that the modified NHL-BFM-90 regimen has better efficacy than R-CHOP in DLBCL patients with advanced-stage disease. However, the R-CHOP regimen might be an option for early-stage DLBCL. Further prospective studies are needed to guide clinical decisions about treatment.

Perinatal Risks of Neonatal and Infant Mortalities in a Sub-provincial Region of China: A Livebirth Population-based Cohort Study.

BACKGROUND: Current vital statistics of birth population and neonatal outcome in China lacked information and definition of deaths at delivery and during hospitalization, especially for extreme preterm (EPT) birth. This study aims to delineate the prevalence of neonatal hospitalization, neonatal and infant mortality rates (NMR, IMR) and associated perinatal risks based on all livebirths in Huai'an, an evolving sub-provincial region in eastern China. METHODS: This retrospective cohort study established a comprehensive database linking information of whole regional livebirths and neonatal hospitalization in 2015, including deaths at delivery and EPT livebirths. The primary outcomes were NMR and IMR stratified by gestational age (GA) and birthweight (BW) with 95% confidence intervals. Causes of the neonatal and infant deaths were categorized according to the International Statistical Classification of Diseases 10th version, and population attributable fractions of GA and BW strata were analyzed. Perinatal risks of infant mortalities in continuum periods were estimated by Cox regression models. RESULTS: Among the whole livebirth population (59056), 7960 were hospitalized (prevalence 13.5%), with 168 (2.8‰) in-hospital deaths. The NMR was 3.6 (3.2, 4.1)‰ and IMR 4.9 (1.4, 4.5)‰, with additionally 35 (0.6‰) deaths at delivery. The major causes of infant deaths were perinatal conditions (2.6‰, mainly preterm-related), congenital anomalies (1.5‰), sudden unexpected death in infancy (0.6‰) and other causes (0.2‰). The deaths caused by preterm and low BW (LBW) accounted for 50% and 40% of NMR and IMR, with 20-30% contributed by EPT or extremely LBW, respectively. Multivariable Cox regression analysis revealed that peripartum factors and LBW strata had strong association with early- and late-neonatal deaths, whereas those of GA < 28 weeks were highly associated with postneonatal deaths. Congenital anomalies and neonatal hospitalization remained high death risks over the entire infancy, whereas maternal co-morbidities/complications were modestly associated with neonatal but not postneonatal infant mortality. CONCLUSIONS: The NMR, IMR, major causes of deaths and associated perinatal risks in continuum periods of infancy, denote the status and quality improvement of the regional perinatal-neonatal care associated with socioeconomic development. The study concept, applicability and representativeness may be validated in other evolving regions or countries for genuine comparison and better maternal-infant healthcare.

Trends and influencing factors of perinatal birth defects in Huai'an from 2008 to 2020.

OBJECTIVE: To analyze the incidence, trends and related factors of birth defects in Huai'an from 2008 to 2020. METHODS: The surveillance data from maternal and child health system of Huai'an from 2008 to 2020 and Huai'an Statistical Yearbook were used for analysis. Taking the annual change percentage and average annual change percentage (AAPC) as the main outcome indicators, the JoinPoint regression analysis was performed to estimate the changing trend of birth defects from 2008 to 2020. Spearman correlation analysis was used to examine the association between birth defects and birth rate, marriage rate, proportion of women with advanced maternal age. RESULTS: During 2008 to 2020, a total of 3414 cases of neonatal birth defects occurred in Huai'an, with an incidence of 4.6‰ (3414/736 608). The rate of perinatal birth defects in Huai'an showed an increasing trend (AAPC=8.8%, t=3.2, P<0.01), and the year of 2016 was a significant changing point. Among 24 types of birth defects, the incidence of congenital heart disease rose and became the most prevalent defect, while the incidence of neural tube malformations such as anencephaly, encephalocele and spina bifida was declined. The incidence of birth defect was negatively correlated with the birth rate ( r=-0.751, P<0.01), not correlated with marriage rate ( r=-0.516, P>0.05), and positively correlated with the proportion of women with advanced maternal age ( r=0.726, P<0.01). CONCLUSION: The incidence of birth defects in Huai'an shows an increasing trend from 2008 to 2020 with congenital heart disease as the most common type of birth defect, and the increase of birth defects incidence is closely related with the increase of the proportion of women with advanced maternal age.

Increased Protection of Earlier Use of Immunoprophylaxis in Preventing Perinatal Transmission of Hepatitis B Virus.

BACKGROUND: Passive-active immunoprophylaxis against mother-to-child transmission (MTCT) of hepatitis B virus (HBV) recommends administering hepatitis B immunoglobulin (HBIG) and birth-dose hepatitis B vaccine in infants within 12 or 24 hours after birth. With this protocol, MTCT of HBV still occurs in 5-10% infants of HBV-infected mothers with positive hepatitis B e antigen (HBeAg). The present study aimed to investigate whether earlier administration of HBIG and hepatitis B vaccine after birth can further increase protection efficacy. METHODS: We conducted a prospective, multi-center observational study in infants born to mothers with HBV infection, in whom neonatal HBIG and birth dose hepatitis B vaccine were administered within one hour after birth. The infants were followed up for HBV markers at 7-14 months of age. RESULTS: A total of 1140 pregnant women with HBV were enrolled, and 982 infants (9 twins) of 973 mothers were followed up at 9.6 ± 1.9 months of age. HBIG and birth-dose vaccine were administered in newborn infants within a median of 0.17 (0.02-1.0) hours after birth. The overall rate of MTCT was 0.9% (9/982), with none (0%) of the 607 infants of HBeAg-negative mothers and 9 (2.4%) of 375 infants of HBeAg-positive mothers acquiring HBV. All 9 HBV-infected infants were born to mothers with HBV DNA >2.75 × 106 IU/mL. Maternal HBV DNA levels >2 × 106 IU/mL were an independent risk factor (odds ratio, 10.627; 95% confidence interval, 2.135-∞) for immunoprophylaxis failure. CONCLUSIONS: Earlier use (within 1 hour after birth) of HBIG and hepatitis B vaccine can provide better protection efficacy against MTCT of HBV.

Association of ADAM10 gene variants with sporadic Parkinson's disease in Chinese Han population.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. Genetic factors play important roles in PD risk. rs653765 and rs514049 of ADAM10 were reported to be associated with Alzheimer's disease (AD) in Caucasian population; however, the association of the two variants with PD in Chinese Han population remains unknown. The present investigation aimed to explore the possible association of ADAM10 variants with PD in Chinese Han population. METHODS: We enrolled 565 PD patients and 518 healthy controls to conduct a case-control study. DNA samples were extracted from peripheral blood leukocytes, and the genotypes were determined by utilization of MassARRAY platform. Plasma levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: We found CC genotype of rs514049 was associated with an increased risk of PD (OR (95% CI) = 3.776 (1.127-11.217), p = 0.018). The C allele frequency of rs514049 was significantly higher in PD group (OR (95% CI) = 1.328 (1.031-1.709), p = 0.028), especially in male subgroup (OR (95% CI) = 1.484 (1.053-2.092), p = 0.024). However, there was no significant difference in the genotype or allele frequencies for rs653765 within the groups. Plasma levels were significantly decreased in PD patients compared with controls (p < 0.001). CONCLUSIONS: Our data suggested that C allele of rs514049 in ADAM10 may increase the risk of PD in Chinese Han population, especially in males. The decreased plasma levels are probably involved in PD development.

Association of CLU gene polymorphism with Parkinson's disease in the Chinese Han population.

BACKGROUND: Clusterin (CLU) plays important role in the pathology of neurodegenerative disorders. Recently, a genetic variant of CLU rs9331896 has been reported as a risk estimate for Alzheimer's disease (AD). However, the association between this variant and the risk of Parkinson's disease (PD) in the Chinese Han population remains elusive. METHODS: We sequenced CLU rs9331896 in 353 PD patients and 326 healthy-matched individuals of the Chinese Han population. The genotypes of rs9331896 were analyzed using MassArray (Agena Bioscience, San Diego, CA, USA) in accordance with the manufacturer's instructions. The distribution of genotypes and allelic frequencies was analyzed by a chi-squared test. Additionally, the expression of CLU protein in plasma was evaluated by an enzyme-linked immunosorbent assay and analysed with a t-test. RESULTS: The TT genotype in rs9331896 in a recessive model was found to be associated with the increased risk of PD (odds ratio = 1.408, 95% confidence interval = 1.034-1.916, p = 0.029). Subgroup analysis indicated that TT genotype carriers showed a significantly higher risk in male PD patients compared to male healthy controls (odds ratio = 1.611, 95% confidence interval = 1.046-2.483, p = 0.030). In addition, CLU levels in the plasma of PD patients were significantly higher than controls (p = 0.024). CONCLUSIONS: The CLU-rs9331896-TT genotype was a risk factor for PD, particularly in males. PD patients also expressed a high level of CLU in plasma.

Molecular and immunophenotypic characterization of anal squamous cell carcinoma reveals distinct clinicopathologic groups associated with HPV and TP53 mutation status.

Squamous cell carcinoma (SqCC) is the most common malignancy of the anal canal, where it is strongly associated with HPV infection. Characteristic genomic alterations have been identified in anal SqCC, but their clinical significance and correlation with HPV status, pathologic features, and immunohistochemical markers are not well established. We examined the molecular and clinicopathologic features of 96 HPV-positive and 20 HPV-negative anal SqCC. HPV types included 89 with HPV16, 2 combined HPV16/HPV18, and 5 HPV33. HPV-positive cases demonstrated frequent mutations or amplifications in PIK3CA (30%; p = 0.027) or FBXW7 mutations (10%). HPV-negativity was associated with frequent TP53 (53%; p = 0.00001) and CDKN2A (21%; p = 0.0045) mutations. P16 immunohistochemistry was positive in all HPV-positive cases and 3/20 HPV-negative cases (p < 0.0001; sensitivity: 100%; specificity: 85%) and was associated with basaloid morphology (p = 0.0031). Aberrant p53 immunohistochemical staining was 100% sensitive and specific for TP53 mutation (p < 0.0001). By the Kaplan-Meier method, HPV-negativity, aberrant p53 staining, and TP53 mutation were associated with inferior overall survival (OS) (p < 0.0001, p = 0.0103, p = 0.0103, respectively) and inferior recurrence-free survival (p = 0.133, p = 0.0064, and p = 0.0064, respectively). TP53/p53 status stratified survival probability by HPV status (p = 0.013), with HPV-negative/aberrant p53 staining associated with the worst OS, HPV-positive/wild-type p53 with best OS, and HPV-positive/aberrant p53 or HPV-negative/wild-type p53 with intermediate OS. On multivariate analysis HPV status (p = 0.0063), patient age (p = 0.0054), T stage (p = 0.039), and lymph node involvement (p = 0.044) were independently associated with OS. PD-L1 expression (CPS ≥ 1) was seen in 30% of HPV-positive and 40% of HPV-negative cases, and PD-L1 positivity was associated with a trend toward inferior OS within the HPV-negative group (p = 0.064). Our findings suggest that anal SqCC can be subclassified into clinically, pathologically, and molecularly distinct groups based on HPV and TP53 mutation status, and p16 and p53 immunohistochemistry represent a clinically useful method of predicting these prognostic groups.

A birth population-based survey of preterm morbidity and mortality by gestational age.

BACKGROUND: Despite 15-17 millions of annual births in China, there is a paucity of information on prevalence and outcome of preterm birth. We characterized the outcome of preterm births and hospitalized preterm infants by gestational age (GA) in Huai'an in 2015, an emerging prefectural region of China. METHODS: Of 59,245 regional total births, clinical data on 2651 preterm births and 1941 hospitalized preterm neonates were extracted from Huai'an Women and Children's Hospital (HWCH) and non-HWCH hospitals in 2018-2020. Preterm prevalence, morbidity and mortality rates were characterized and compared by hospital categories and GA spectra. Death risks of preterm births and hospitalized preterm infants in the whole region were analyzed with multivariable Poisson regression. RESULTS: The prevalence of extreme, very, moderate, late and total preterm of the regional total births were 0.14, 0.53, 0.72, 3.08 and 4.47%, with GA-specific neonatal mortality rates being 44.4, 15.8, 3.7, 1.5 and 4.3%, respectively. There were 1025 (52.8% of whole region) preterm admissions in HWCH, with significantly lower in-hospital death rate of inborn (33 of 802, 4.1%) than out-born (23 of 223, 10.3%) infants. Compared to non-HWCH, three-fold more neonates in HWCH were under critical care with higher death rate, including most extremely preterm infants. Significantly all-death risks were found for the total preterm births in birth weight <  1000 g, GA < 32 weeks, amniotic fluid contamination, Apgar-5 min < 7, and birth defects. For the hospitalized preterm infants, significantly in-hospital death risks were found in out-born of HWCH, GA < 32 weeks, birth weight <  1000 g, Apgar-5 min < 7, birth defects, respiratory distress syndrome, necrotizing enterocolitis and ventilation, whereas born in HWCH, antenatal glucocorticoids, cesarean delivery and surfactant use decreased the death risks. CONCLUSIONS: The integrated data revealed the prevalence, GA-specific morbidity and mortality rate of total preterm births and their hospitalization, demonstrating the efficiency of leading referral center and whole regional perinatal-neonatal network in China. The concept and protocol should be validated in further studies for prevention of preterm birth.

Comparative analysis of excretion of six major compounds of Polygonum orientale L. extract in urine, feces and bile under physiological and myocardial ischemia conditions in rats using UPLC-MS/MS.

Polygonum orientale L. is a traditional Chinese medicine having extensive pharmacological activities including antimyocardial ischemia (MI) injury properties. Isoorientin, orientin, vitexin, quercitrin, astragalin and protocatechuic acid are the main compounds in P. orientale extract. The aim of this study was to establish an ultra-performance liquid chromatography-tandem mass spectrometry method for the determination of the content of these compounds in urine, feces and bile samples simultaneously and application of the method in a comparative excretion study in normal and MI model rats after oral administration of P. orientale extract. Chromatographic seperation was conducted on an Agilent Eclipse Plus C18 column with the mobile phase consisting of 0.1% formic acid-acetonitrile and 0.1% formic acid-water. Negative ion multiple reaction monitoring mode was used for quantification. The six compounds had good linearity (r ≥ 0.9921) and acceptable accuracy ranging from 10.10 to -5.82% The relative standard deviations of within-day precision and inter-day precision were <10.45 and 13.44%, respectively. The extraction recovery of the six analytes ranged from 80.31 to 101.47% and the matrix effect was 82.56-102.88%, indicating that the preparations of sample collected form urine, feces and bile were stable throughout analysis. The excretion amount of the six analytes increased in both normal and MI model rats' urine, feces and bile in a 24 h period and became stable between 36 and 48 h after administration. The total excretion rate of six compounds was <5% in urine, feces and bile of normal and MI model rats. The excretion peak period for all compounds in MI rats was slower than that in normal rats. This excretion study provides insights for further application and research on P. orientale.

CD56 expression in basaloid anal squamous cell carcinoma - A potential diagnostic pitfall.

Anal squamous cell carcinoma (SqCC) is a morphologically heterogeneous entity. Basaloid and non-keratinizing anal SqCC may be confused with other tumors including neuroendocrine carcinoma due to morphologic overlap, and expression of neuroendocrine markers is not well-studied in anal SqCC. Prompted by a case of anal SqCC that was initially misdiagnosed as neuroendocrine carcinoma on the basis of morphology and CD56 expression, we retrospectively examined the expression of neuroendocrine markers CD56, synaptophysin, and chromogranin in 48 cases of basaloid anal SqCC, with clinicopathologic correlation. HPV16 was identified in 46 cases, HPV33 in one case, and one case was HPV-negative. Three (6.3%) cases demonstrated CD56 expression, including two with diffuse and one with focal expression. Two CD56-positive cases demonstrated basaloid morphology with peripheral palisading and the other demonstrated adenoid cystic/cylindroma-like morphology. None of the cases showed significant synaptophysin or chromogranin expression. The three cases expressing CD56 were HPV16-positive, and one demonstrated a CTNNB1 mutation. There was no difference in clinicopathologic features including stage, outcome, or HPV status, between CD56-positive and negative groups. Our findings support that CD56 expression is infrequently expressed in anal SqCC and is not indicative of neuroendocrine differentiation in the absence of expression of more specific neuroendocrine markers such as synaptophysin and chromogranin. Pathologists should be aware that CD56 expression may occur in basaloid anal SqCC and is a diagnostic pitfall due to morphologic overlap with neuroendocrine carcinoma and other tumors including basal cell carcinoma.

Microglial P2Y12 Receptor Regulates Seizure-Induced Neurogenesis and Immature Neuronal Projections.

Seizures are common in humans with various etiologies ranging from congenital aberrations to acute injuries that alter the normal balance of brain excitation and inhibition. A notable consequence of seizures is the induction of aberrant neurogenesis and increased immature neuronal projections. However, regulatory mechanisms governing these features during epilepsy development are not fully understood. Recent studies show that microglia, the brain's resident immune cell, contribute to normal neurogenesis and regulate seizure phenotypes. However, the role of microglia in aberrant neurogenic seizure contexts has not been adequately investigated. To address this question, we coupled the intracerebroventricular kainic acid model with current pharmacogenetic approaches to eliminate microglia in male mice. We show that microglia promote seizure-induced neurogenesis and subsequent seizure-induced immature neuronal projections above and below the pyramidal neurons between the DG and the CA3 regions. Furthermore, we identify microglial P2Y12 receptors (P2Y12R) as a participant in this neurogenic process. Together, our results implicate microglial P2Y12R signaling in epileptogenesis and provide further evidence for targeting microglia in general and microglial P2Y12R in specific to ameliorate proepileptogenic processes.SIGNIFICANCE STATEMENT Epileptogenesis is a process by which the brain develops epilepsy. Several processes have been identified that confer the brain with such epileptic characteristics, including aberrant neurogenesis and increased immature neuronal projections. Understanding the mechanisms that promote such changes is critical in developing therapies to adequately restrain epileptogenesis. We investigated the role of purinergic P2Y12 receptors selectively expressed by microglia, the resident brain immune cells. We report, for the first time, that microglia in general and microglial P2Y12 receptors in specific promote both aberrant neurogenesis and increased immature neuronal projections. These results indicate that microglia enhance epileptogenesis by promoting these processes and suggest that targeting this immune axis could be a novel therapeutic strategy in the clinic.

Identification of mini-chromosome maintenance 8 as a potential prognostic marker and its effects on proliferation and apoptosis in gastric cancer.

Mini-chromosome maintenance (MCM) proteins play important roles in initiating eukaryotic genome replication. The MCM family of proteins includes several members associated with the development and progression of certain cancers. We performed online data mining to assess the expression of MCMs in gastric cancer (GC) and the correlation between their expression and survival in patients with GC. Notably, MCM8 expression was undoubtedly up-regulated in GC, and higher expression correlated with shorter overall survival (OS) and progression-free survival (PFS) in patients with GC. However, the role of MCM8 in GC has not been previously explored. Our in vitro experiments revealed that MCM8 knockdown inhibited cell growth and metastasis. Moreover, MCM8 knockdown induced apoptosis. Mechanistically, the expression levels of Bax and cleaved caspase-3 were increased, whereas Bcl-2 expression decreased. Additionally, we demonstrated that MCM8 knockdown suppressed tumorigenesis in vivo. Overall, these results suggest that MCM8 plays a significant role in GC progression.

Inhibition of NMDA Receptors Downregulates Astrocytic AQP4 to Suppress Seizures.

Aquaporin 4 (AQP4), a water-specific channel protein locating on the astrocyte membrane, has been found to be antagonist, agonist and undergone closely related to epilepsy. Our previous study showed that inhibition of an N-methyl-D-aspartate receptor (NMDAR) subunit NR2A can suppress epileptic seizures, suggesting that AQP4 is potentially involved in NR2A-mediated epilepsy treatment. In this study, we aimed to explore the relevance of AQP4 in NR2A-mediated seizures treatment in pentylenetetrazol (PTZ)-induced rat models. We performed electroencephalogram (EEG) recording and examined AQP4 expression at mRNA and protein levels, and the downstream molecules of AQP4 as well. It showed that AQP4 expression was increased after the induction of seizures. Lateral ventricle pretreatment of NR2A inhibitor could mitigate the PTZ-induced seizures severity and counterbalance the increase of AQP4 expression. In contrast, NR2A activator that resulted in seizures aggravation could further augment the seizure-related elevations of AQP4 expression. Pharmacological inhibition of AQP4 alone could also suppress the PTZ-induced seizure activities, with decreased expressions of NF-κB p65, interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-α in the brain. The results indicated that increased expression of AQP4 might be an important mechanism involved in NR2A of NMDAR-mediated treatment for epileptic seizures, enlightening a potentially new target for seizures treatment.

Non-Contact Monitoring on the Flow Status inside a Pulsating Heat Pipe.

The paper presents a concept of thermal-to-electrical energy conversion by using the oscillatory motion of magnetic fluid slugs which has potential to be applied in the field of sensors. A pulsating heat pipe (PHP) is introduced to produce vapor-magnetic fluid plug-slug flow in a snake-shaped capillary tube. As the magnetic fluid is magnetized by the permanent magnet, the slugs of magnetic fluid passing through the copper coils make the magnetic flux vary and produce the electromotive force. The peak values of induced voltage observed in our tests are from 0.1 mV to 4.4 mV. The effects of the slug velocity, heat input and magnetic particle volume concentration on the electromotive force are discussed. Furthermore, a theoretical model considering the fluid velocity of the working fluid, the inner radius of the PHP and the contact angle between the working fluid and the pipe wall is established. At the same time, the theoretical and experimental results are compared, and the influences of tube inner radius, working fluid velocity and contact angle on the induced electromotive force are analyzed.

GuaLou GuiZhi decoction represses LPS-induced BV2 activation via miR-155 induced inflammatory signals.

Inflammatory response that occur post-ischemia is a serious problem in the treatment of ischemic brain disease. MicroRNA-155 is a brain-specific or brain-enriched miRNA, which mediates inflammatory reactions in cerebral ischemic tissue by regulating inflammatory signal and the expression level of SOCS1. The present study was aimed to assess the effect of GuaLou GuiZhi Decoction (GLGZD) on miR-155 expression in activated microglia following inflammation and further explore the role of GLGZD on expression of the inflammation-related gene. BV2 cells were used to simulated by LPS to make the inflammatory model. Expression level of miR-155 was detected by Real-Time PCR. BV2 cells after simulated by LPS were then transfected with miR-155 mimic and its negative controls. Cytokines release were measured by corresponding purchased ELISA kits, respectively. Then target protein expression of miR-155 were detected by western blotting assay. After miRNA over expression transfections, expressions of inflammation-related factors, SOCS-1 and SAMD in BV2 cells after activation were measured by Western blot assay. Results showed that in BV2 cells after simulated by LPS, miR-155 was upregulated. The elevated miR-155 expression enhanced the inflammatory cytokine release. miR-155 directly target and negatively regulated SOCS-1 and SMAD-1 expression. Over expression of SOCS-1 and SMAD reduced inflammatory action that was enhanced by miR-155 mimic transfection. miR-155 was positively related with activation of NF-Ï°B signal pathways via SOCS-1 and SMAD. In conclusion, GuaLou GuiZhi Decoction (GLGZD) might exert its anti-inflammatory action by inhibiting the expression of miR-155, indicating that miR-155 may be used as a treatment target in clinical treatment with GuaLou GuiZhi Decoction (GLGZD) in ischemic brain.

hsa_circRNA_100533 regulates GNAS by sponging hsa_miR_933 to prevent oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is the most common malignant tumor of the head and neck region. Circular RNA (circRNA), as one kind of noncoding RNA, involves in biological processes in diverse cancers. circRNA functions mainly as the microRNA (miRNA) sponge, competitively binding to miRNAs to regulate target gene expressions. However, the expression profiles and roles of circRNAs in OSCC are still unexplored. circRNA microarrays and quantitative real-time polymerase chain reaction was used to identify the hsa_circRNA_100533 downregulated in OSCC tissues and cell lines. Bioinformatics methods were used to predict the interactions among circRNAs, miRNA, and target genes. Based on the luciferase reporter assay and AGO2 RIP assay, we found that hsa_circRNA_100533 binds to miRNAs as a miRNA sponge. hsa_circRNA_100533 inhibited cell proliferation, migration, and promoted cell apoptosis in OSCC cell lines, which could be blocked by hsa-miR-933 overexpression. hsa_circRNA_100533 binds to hsa-miR-933 as a miRNA sponge to regulate GNAS expression, and to modulate cell proliferation, migration, and apoptosis. In summary, the hsa_circRNA_100533-miR-933-GNAS axis affect the proliferation and apoptosis of OSCC cells through the mechanism of competing endogenous RNAs. hsa_circRNA_100533 may function as promising diagnostic biomarkers and effective therapeutic targets for OSCC.