Geraniol (GER) attenuated chronic sleep restriction (CSR)-induced neuroinflammation in adolescent mice.

Sleep insufficiency is a significant health problem worldwide, and adolescent sleep restriction (SR) could induce multiple neurodevelopmental disorders in the central nervous system (CNS). Microglial-mediated neuroinflammation plays a vital role in multiple neurological diseases, and recent research showed the regulation effect of immunoproteasome on microglia functions. Geraniol (GER), an important ingredient in many essential oils, possesses diverse pharmacological properties like anti-inflammatory and antioxidant. The present study was designed to evaluate the neuroprotective effect of GER on SR in adolescent mice and further investigate the underlying mechanisms. Our results displayed that 14 days of chronic sleep restriction (CSR) induced cognitive decline, and anxiety-like and attention-deficit behaviors, which were mitigated by GER pretreatment. GER administration also reversed microglial pro-inflammatory response under CSR stimulation in the anterior cingulate cortex (ACC) regions by reducing the expression and secretion of cytokines like IL-1ß and TNF-α. Mechanism research showed that LMP7 mRNA was selectively up-regulated under CSR treatment but down-regulated by GER administration. Proteasome activity and protein expression of LMP7 were consistent with mRNA data. ONX-0914 was applied to inhibit LMP7 selectively, and data validated that GER might alleviate CSR-induced neuroinflammation by regulating LMP7. Our study provides evidence that LMP7 is a critical regulator of CSR-induced proinflammation, and geraniol might be a promising therapy against CSR-induced neurodevelopmental disorders.

Effects of ultrasound on the degradation kinetics, physicochemical properties and prebiotic activity of Flammulina velutipes polysaccharide.

The controllable ultrasonic modification was hindered due to the uncertainty of the relationship between ultrasonic parameters and polysaccharide quality. In this study, the ultrasonic degradation process was established with kinetics. The physicochemical properties and prebiotic activity of ultrasonic degraded Flammulina velutipes polysaccharides (U-FVPs) were investigated. The results showed that the ultrasonic degradation kinetic models were fitted to 1/Mt-1/M0 = kt. When the ultrasonic intensity increased from 531 to 3185 W/cm2, the degradation proceeded faster. The decrease of polysaccharide concentration contributed to the degradation of FVP, and the fastest degradation rate was at 60 °C. Ultrasound changed the solution conformation of FVP, and partially destroyed the stability of the triple helix structure of FVP. Additionally, the viscosity and gel strength of FVP decreased, but its thermal stability was improved by ultrasound. Higher ultrasonic intensity led to larger variations in physicochemical properties. Compared with FVP, U-FVPs could be more easily utilized by gut microbiota. U-FVPs displayed better prebiotic activity by promoting the growth of Bifidobacterium and Brautella and inhibiting the growth of harmful bacteria. Ultrasound could be effectively applied to the degradation of FVP to improve its physicochemical properties and bioactivities.

A functional methylation signature to predict the prognosis of Chinese lung adenocarcinoma based on TCGA.

BACKGROUND: Lung cancer is the leading cause of cancer morbidity and mortality worldwide, however, the individualized treatment is still unsatisfactory. DNA methylation can affect gene regulation and may be one of the most valuable biomarkers in predicting the prognosis of lung adenocarcinoma. This study was aimed to identify methylation CpG sites that may be used to predict lung adenocarcinoma prognosis. METHODS: The Cancer Genome Atlas (TCGA) database was used to detect methylation CpG sites associated with lung adenocarcinoma prognosis and construct a methylation signature model. Then, a Chinese cohort was carried out to estimate the association between methylation and lung adenocarcinoma prognosis. Biological function studies, including demethylation treatment, cell proliferative capacity, and gene expression changes in lung adenocarcinoma cell lines, were further performed. RESULTS: In the TCGA set, three methylation CpG sites were selected that were associated with lung adenocarcinoma prognosis (cg14517217, cg15386964, and cg18878992). The risk of mortality was increased in lung adenocarcinoma patients with the gradual increase level of methylation signature based on three methylation sites levels (HR = 45.30, 95% CI = 26.69-66.83; p < 0.001). The C-statistic value increased to 0.77 when age, gender, and other clinical variables were added to the signature to prediction model. A similar situation was confirmed in Chinese lung adenocarcinoma cohort. In the biological function studies, the proliferative capacity of cell lines was inhibited when the cells were demethylated with 5-aza-2'-deoxycytidine (5-aza-2dC). The mRNA and protein expression levels of SEPT9 and HIST1H2BH (cg14517217 and cg15386964) were downregulated with different concentrations of 5-aza-2dC treatment, while cg18878992 showed the opposite result. CONCLUSION: This study is the first to develop a three-CpG-based model for lung adenocarcinoma, which is a practical and useful tool for prognostic prediction that has been validated in a Chinese population.

The structure-activity mechanism of the changes in the physicochemical properties of Flammulina velutipes polysaccharides during ultrasonic extraction.

BACKGROUND: The high yield of ultrasonic extraction has been widely studied. However, the effects of ultrasound on the properties of products has generally been ignored. In this study, the structural characteristics, rheological properties, and thermal stability of Flammulina velutipes polysaccharides (FVPs) under different ultrasonic power (200, 600, 1000 W) and time (10, 20, 30 min) were investigated to explore the effects of ultrasonic extraction on FVPs and the structure-physicochemical properties relationship. The ultrasonic intensity at the corresponding rated power was also measured. RESULTS: The results showed that the molecular weight, particle size, and zeta potential of FVPs decreased as the ultrasonic intensity or time increased. The galactose, mannose, and fucose contents were increased, but the glucose content was decreased by ultrasonic extraction. Viscosity and weak gel strength were positively correlated with molecular weight. Thermal degradation enthalpy was positively correlated with the galactose and fucose contents. CONCLUSIONS: Ultrasound reduced the viscosity and gel strength of FVPs by breaking the polysaccharide chain and improving the galactose and fucose contents, which improved the thermal stability of FVPs. This work provides a theoretical basis for the development of FVP foods with a clear structure-function relationship, which makes it possible to directionally produce FVPs by adjusting ultrasonic parameters during extraction. © 2021 Society of Chemical Industry.

Risk factors for severe hand, foot, and mouth disease infected with Coxsackievirus A6: A hospital-based case-control study.

Coxsackievirus 6 (CV-A6) has been emerging as another predominant serotype for severe hand, foot, and mouth disease (HFMD) in China, after the introduction of enterovirus 71 inactivated vaccine (EV71 vaccine) for 3 years. Data on the risk factors for severe HFMD infected with CV-A6 are limited. We interviewed the caregivers to collected data on HFMD patients who sought medical care in the People's Hospital of Baoan district, Shenzhen, from 2015 to 2017. Totally, 131 severe patients were frequency-matched by age and gender with 174 mild patients infected with CV-A6. Univariable and multivariable logistic regression analyses were conducted to analyze the risk factors for severe CV-A6 HFMD. The average age was 20.62 ± 14.18 months and 20.52 ± 12.76 months for severe and mild patients, respectively. Multivariate analyses indicated complications at birth (odds ratio [OR], 4.18; 95% confidence interval [CI]: 1.64-10.63), peak body temperature over 39°C (OR, 4.04; 95% CI: 2.29-7.10) and first-born child (OR, 2.17; 95% CI: 1.27-3.70) increased the risk of severe HFMD infected with CV-A6. Breastfeeding (OR, 0.52; 95% CI: 0.32-0.87), and washing hands after playing frequently (OR, 0.58; 95% CI: 0.34-0.97) were negatively associated with severe illness. Compared with HFMD with infection of EV-A71, complications at birth and first-born child were newly found to be associated with severe illness in HFMD patients infected with CV-A6.

Genome-wide association study identifies TPH2 variant as a novel locus for severe CV-A6-associated hand, foot, and mouth disease in Han Chinese.

BACKGROUND: Little is known about the association between genetic susceptibility and the severity of hand, foot, and mouth disease (HFMD) infected with coxsackievirus A6 (CV-A6). METHODS: Three hundred and sixty-four CV-A6 HFMD patients were enrolled, including 115 severe and 249 mild patients. A genome-wide association study (GWAS) was performed involving eight DNA pools of 115 severe and 115 mild CV-A6 HFMD patients pair-matched by age and gender. Differences in relative allele signal scores of SNPs in Illumina Human OmniZhongHua-8 BeadChips were compared between the two groups. The tag SNPS for potentially functional SNPs or their high linked SNPs were selected for individual genotyping in all 364 patients and assessed for their associations with severe CV-A6 HFMD using multivariable logistic regression analyses. RESULTS: The top 30 significant SNPs obtained from pooled DNA GWAS analysis were checked for biological functions and their high linkage disequilibrium (LD) SNPs. Four tag SNPs (rs1558206, rs6927647, rs9375728 and rs10879355) were selected for further individual genotyping in 364 CV-A6 patients. Only SNP rs10879355 was associated with severe CV-A6 HFMD, with CC genotype having a greater risk of severe illness than TT+TC genotypes (OR=2.48, 95%CI: 1.34, 4.56). SNP rs4290270 is in complete LD with rs10879355 in Chinese Han children. CONCLUSIONS: This is the first report that one potentially functional SNP rs4290270 in the TPH2 gene may be associated with the risk of severe CV-A6 HFMD.

Association between Fas/FasL gene polymorphism and musculoskeletal degenerative diseases: a meta-analysis.

BACKGROUND: It was reported that Fas (rs1800682, rs2234767) and FasL (rs5030772, rs763110) gene polymorphism might be related to the risk of musculoskeletal degenerative diseases (MSDD), such as osteoarthritis (OA), intervertebral disc degeneration (IVDD) and rheumatoid arthritis (RA). However, data from different studies was inconsistent. Here we aim to elaborately summarize and explore the association between the Fas (rs1800682, rs2234767) and FasL (rs5030772, rs763110) and MSDD. METHODS: Literatures were selected from PubMed, Web of Science, Embase, Scopus and Medline in English and VIP, SinoMed, Wanfang and the China National Knowledge Infrastructure (CNKI) in Chinese up to August 21, 2017. All the researches included are case-control studies about human. We calculated the pooled odds ratios (ORs) with 95% confidence intervals (95% CI) to evaluate the strengths of the associations of Fas (rs1800682, rs2234767) and FasL (rs5030772, rs763110) polymorphisms with MSDD risk. RESULTS: Eleven eligible studies for rs1800682 with 1930 cases and 1720 controls, 6 eligible studies for rs2234767 with 1794 cases and 1909 controls, 3 eligible studies for rs5030772 with 367 cases and 313 controls and 8 eligible studies for rs763110 with 2010 cases and 2105 controls were included in this analysis. The results showed that the G allele of Fas (rs1800682) is associated with an increased risk of IVDD in homozygote and recessive models. The G allele of Fas (rs2234767) is linked to a decreased risk of RA but an enhanced risk of OA in allele and recessive models. In addition, the T allele of FasL (rs763110) is correlated with a reduced risk of IVDD in all of models. However, no relationship was found between FasL (rs5030772) and these three types of MSDD in any models. CONCLUSIONS: Fas (rs1800682) and FasL (rs763110) polymorphism were associated with the risk of IVDD and Fas (rs2234767) was correlated to the susceptibility of OA and RA. Fas (rs1800682) and Fas (rs2234767) are more likely to be associated with MSDD for Chinese people. FasL (rs763110) is related to the progression of MSDD for both Caucasoid and Chinese race groups. But FasL (rs5030772) might not be associated with any types of MSDD or any race groups statistically.

Fe3S4 Nanoparticles Wrapped in an rGO Matrix for Promising Energy Storage: Outstanding Cyclic and Rate Performance.

Iron sulfides/oxides/fluorides have been profoundly investigated as electrodes for rechargeable batteries recently in view of their high-theory capacities, low cost, and environmentally benign nature. Here, Fe3S4 nanoparticles (NPs) wrapped in reduced graphene oxide (Fe3S4 NPs@rGO) have been obtained using a simple one-pot hydrothermal approach, which is characterized using various techniques. As the anode for Li-ion batteries, Fe3S4 NPs@rGO displays a reversible discharge capacity of 950 mA h/g after 100 cycles at 0.1 A/g, and 720 mA h/g capacity can be achieved after 800 cycles even at 1 A/g. Even at 10 A/g, 462 mA h/g capacity can be maintained. The excellent electrochemical properties for Fe3S4 NPs@rGO can be ascribed to a collaborative effect between Fe3S4 NPs and an rGO matrix, which possess high Li-ion storage ability and excellent conductivity, respectively.

Comparison of Continuous Noninvasive Blood Pressure Monitoring by TL-300 With Standard Invasive Blood Pressure Measurement in Patients Undergoing Elective Neurosurgery.

BACKGROUND: Intraoperative blood pressure (BP) is one of the basic vital signs monitoring. Compared with standard invasive BP measurement, TL-300 allows for a continuous and beat-to-beat noninvasive intraoperative BP monitoring. The current retrospective study compared the accuracy and precision of this noninvasive technique for continuous BP monitoring with that of standard invasive BP measurement in patients undergoing elective neurosurgery. MATERIALS AND METHODS: BP records of 23 patients undergoing elective neurosurgery, measured by both noninvasive TL-300 and invasive radial arterial catheter method, were retrospectively analyzed. Variability in BP data was analyzed by using linear regressions and Bland-Altman analysis. RESULTS: Four thousand three hundred eighty-one pairs of BP measurements from a total of 23 patients were included. The coefficient of determination of systolic, diastolic, and mean BP were 0.908, 0.803, and 0.922, respectively. And their bias was found to be 1.3±5.87 mm Hg (95% limits of agreement: -10.2 to +12.8 mm Hg), 2.8±6.40 mm Hg (95% limits of agreement: -9.8 to +15.3 mm Hg), and 1.8±4.20 mm Hg (95% limits of agreement: -6.4 to +10.1 mm Hg), respectively. CONCLUSIONS: TL-300 system is a promising noninvasive alternative to the invasive arterial catheter method for intraoperative BP monitoring, with a high accuracy and precision. With the limitation of the current retrospective study, further prospective method comparison studies are needed.

Neuromuscular effect of dexmedetomidine on sevoflurane: an open-label, dose-escalation clinical trial.

BACKGROUND: Sevoflurane presents reliable central neuromuscular effects. However, little knowledge is available regarding the interaction between sevoflurane and demedetomidine. We evaluated the neuromuscular effect of dexmedetomidine on sevoflurane in patients with normal neuromuscular transmission and calculated the 50% effective concentration (EC50). METHODS: One-hundred and forty-four ASA grade I~II patients with normal neuromuscular transmission, aged 20~60 years old, undergoing lower limbs surgery were enrolled in this open-label, dose-escalation clinical trial. Patients were randomly assigned into 12 groups. Each patient received intravenous 0, 0.5, or 1.0 µg/kg dexmedetomidine 15 min after inhaling 0.7, 1.0, 1.4, or 2.0 MAC sevoflurane. Neuromuscular monitoring was recorded from the adductor pollicis muscle by using acceleromyography with train-of-four (TOF) stimulation of the ulnar nerve (2 Hz every 20 s). TOF ratio was recorded before inhaling sevoflurane, 15 min after keeping constant at target MAC of sevoflurane, 30 min after receiving target dose of dexmedetomidine, and 15 min after sevoflurane washing out. RESULTS: Sevoflurane produced a concentration-dependent decrease in TOF ratio. Mean TOF ratio in 0.7, 1.0, 1.4, and 2.0 MAC groups was 97.9%, 94.9%, 84.7%, and 77.2%, respectively. Neuromuscular EC50 of sevoflurane was 1.31 MAC (95% CI: 1.236~1.388 MAC). Intravenous 0.5 and 1.0 µg/kg dexmedetomidine decreased 3.1% (EC50: 1.27 MAC [95% CI: 1.206~1.327 MAC]) and 10.7% (EC50: 1.17 MAC [95% CI: 1.122~1.217 MAC]) of neuromuscular EC50, respectively. CONCLUSIONS: Sevoflurane has a concentration-dependent central neuromuscular effect in patients with normal neuromuscular transmission. Intravenous dexmedetomidine dose-dependently decreases the neuromuscular EC50 of sevoflurane.

The pattern and prevalence of lymphatic spread in thoracic oesophageal squamous cell carcinoma.

BACKGROUND: Oesophageal squamous cell carcinoma (SCC) is a common type of cancer in China. The knowledge of its pattern of lymphatic metastasis would be of clinical value for surgical and radiation oncologists to treat this disease. MATERIAL AND METHODS: A large series of 1850 thoracic oesophageal SCC was retrospectively analysed after extended oesophagectomy with three-field lymphadenectomy (3FL). Specimens were assessed for pattern of lymphatic spread. RESULT: Of the 1850 patients, 1081 (58.4%) developed mediastinal, cervical and/or abdominal node metastases. The lymphatic metastasis rates were 35.6%, 22.2%, 26.5%, 6.1% and 26.5%, respectively, for the cervical, upper, middle, lower mediastinal nodes and abdominal nodes. The adjacent mediastinal node metastasis alone occurred in 5.5% of patients, and the multiple level or skip node spread accounted for 20.9% and 73.6% of patients with node metastases. Upward lymphatic spread developed in 46.4% of patients, both up- and downward in 33.2%, and the downward, 20.5%. For the upper oesophageal SCC, the most common node metastasis was in the cervical (49.5%) and followed by the upper mediastinal (28.7%), middle mediastinal (11.4%), abdominal (8.0%) and lower mediastinal (1.4%) nodes. For the middle oesophageal SCC, the highest incidence of node spread was also in the cervical (35.0%) and similar rates in the middle mediastinal (29.8%), abdominal (27.2%) and upper mediastinal (22.4%) nodes, but the least in the lower mediastinal (6.0%) node. For the lower oesophageal SCC, more node metastasis occurred in the abdominal (51.7%), and followed by the middle mediastinal (25.6%), cervical (17.2%), lower mediastinal (13.9%) and upper mediastinal (10.0%). However, the lymphatic metastasis rates of the upper, middle and lower thoracic oesophageal SCC were similar. The unfavourable factors for lymphatic metastasis were long oesophageal lesion (p<0.000), late T stage (p<0.000) and poor differentiation of tumour cells (p<0.000). CONCLUSION: The prevalence was: (1) lymphatic spread prone to the upward in the upper oesophageal SCC, downward in the lower one and both up- and downward in the middle one with in favour of the upward and (2) multiple level and skip node metastases were very often seen. The unfavourable factors for node spread were long oesophageal lesion, late T stage and poor differentiation of tumour cells.