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Abstract Background As precision medicine gradually played an inaccessible role in cancer treatment, there was an urgent need to explore biomarkers or signatures for predicting cancer prognosis. Currently, little was known about the associations between COLGALT1 and kidney renal clear cell carcinoma (KIRC). Hence, this study was performed to reveal its roles in KIRC and to identify potential mechanisms of competing endogenous RNA (ceRNA) networks. Methods R 4.1.1 software was utilized to conduct bioinformatics analyses with the data derived from online databases. Difference analysis, survival analysis, univariate/multivariate cox regression analysis and correlation analysis were carried out successively in this article. Besides, we also investigated potential effects and mechanisms of COLGALT1 in KIRC. Results COLGALT1 expression was overexpressed in KIRC samples compared with the normal samples and it was associated with poor OS (P

Abstract As emerging next-generation information technologies, blockchains have unique advantages in information transparency and transaction security. They have attracted great attentions in social and financial fields. However, the rapid development of quantum computation and the impending realization of quantum supremacy have had significant impacts on the advantages of traditional blockchain based on traditional cryptography. Here, we propose a blockchain algorithm based on asymmetric quantum encryption and a stake vote consensus algorithm. The algorithm combines a consensus algorithm based on the delegated proof of stake with node behaviour and Borda count (DPoSB) and quantum digital signature technology based on quantum state computational distinguishability with a fully flipped permutation ( $${\text{QSC}}{\text{D}}_{\text{ff}}$$ QSCD ff ) problem. DPoSB is used to generate blocks by voting, while the quantum signature applies quantum one-way functions to guarantee the security of transactions. The analysis shows that this combination offers better protection than other existing quantum-resistant blockchains. The combination can effectively resist the threat of quantum computation on blockchain technology and provide a new platform to ensure the security of blockchain.

Abstract Background Selinexor 80 mg combined with low-dose dexamethasone (Sd) demonstrated significant clinical benefit in patients with relapsed/refractory multiple myeloma (RRMM) who had disease refractory to a proteasome inhibitor (PI), an immunomodulator (IMiD), and an anti-CD38 monoclonal antibody based on a global phase II STORM study. The present study, MARCH, addresses China regulatory needs to further validate the data from STORM in Chinese patients with RRMM. Methods The MARCH study was conducted at 17 sites in China, where eligible Chinese RRMM patients who had disease refractory to PI and IMiD were enrolled. Selinexor 80 mg combined with dexamethasone 20 mg was administered orally on day 1 and day 3 of each week in 4-week cycles. The primary endpoint was the overall response rate (ORR) per an independent review committee, with the null hypothesis of ≤15%. Patients who received at least 1 dose of study treatment were included in the safety population. The pharmacokinetic (PK) profile was characterized by parameter and ethnicity sensitivity analyses. Results A total of 82 patients with RRMM were enrolled in the study, with a median age of 60 years. Of the 82 patients, 55 patients (67.1%) had high-risk cytogenetic abnormalities, defined as one or more of del 17p13, t(4;14), t(14;16), or 1q amplification identified by fluorescence in situ hybridization (FISH); 18 patients (22.0%) had abnormal renal function. Enrolled patients were heavily pre-treated with a median prior regimen number of 5. All 82 patients (100%) were refractory to both PI and IMiD, including 20 patients (24.4%) categorized as triple-class refractory population (refractory to PI, IMiD, and daratumumab). Ten patients (12.2%) had undergone CAR-T therapy. ORR was 29.3% (95% CI 19.7, 40.4) with a median DOR of 4.7 months. The median PFS and OS were 3.7 and 13.2 months, respectively. ORR was 25.0% (95% CI 8.7, 49.1) in the triple-class refractory population. Efficacy was consistent across various subgroups. The most frequent grade 3/4 adverse events (AEs) included anemia (57.3%), thrombocytopenia (51.2%), lymphopenia (42.7%), neutropenia (40.2%), hyponatremia (29.3%), and lung infection (26.8%). Serious AEs were reported in 54.9% of patients. No significant drug accumulation was shown following multiple administrations. No human PK ethnicity difference was identified between Chinese and western patients. Conclusions With an encouraging ORR, the MARCH study has demonstrated that selinexor combined with low-dose dexamethasone (Sd) delivers meaningful clinical benefit to Chinese patients with RRMM, including triple-class refractory patients. AEs were expected and manageable with supportive care and dose modification. Trial registration ClinicalTrials.gov, NCT03944057 (May 09, 2019); Chinadrugtrials.org.cn , CTR20190858 (June 05, 2019)

Abstract Regardless of technical advancements, delayed bleeding is still a common adverse event after gastric endoscopic submucosal dissection (ESD), often occurring in the early postoperative phase. This study aimed to evaluate the efficacy of a newly designed polyethylene oxide (PEO) adhesive for preventing delayed gastric bleeding. Patients who underwent gastric ESD between December 2017 and December 2020 at three Chinese institutions were retrospectively reviewed. Patients receiving PEO application on gastric post-ESD ulcers were included in the PEO group, and patients without this procedure were included in the control group. To minimize potential bias, propensity score matching was performed, and sex, age, lesion size, lesion morphology, ulceration, localization, procedure time, frequency of major intraoperative bleeding, resected specimen size, lesion histopathology, submucosal invasion and the taking of antithrombotic drugs were included as matching factors. The incidence of delayed bleeding and time to bleeding were compared between both groups. After propensity score matching, 270 patients (135 per group) were included in the analysis. The delayed bleeding rate in the PEO group was significantly lower than that in the control group (1.5%, 2/135 vs. 8.9%, 12/135, P = 0.006). The median time (range) to bleeding was 4.5 (4–5) days in the PEO group and 2 (1–15) days in the control group, with no significant difference (P = 0. 198). PEO demonstrated a significant effect in reducing the rate of delayed bleeding. Further study is warranted to confirm the efficacy of PEO for bleeding that occurs in the early phase after gastric ESD.

Abstract. Whether a fish-rich diet is positively associated with cognitive function after stroke remains unclear; thus, the present study investigated the relationship between them. The present study was part of a prospective multicenter study, in which 920 individuals (609 males, mean age, 62.78 ± 11.79 years) were included from November 2013 to December 2015. The cognitive function of the patients was evaluated, and the diagnosis of poststroke cognitive impairment (PSCI) was made during their stay in the hospital. A subgroup of 439 patients from a single center was followed up for 4 to 6 years and was reassessed for cognitive function. According to the diagnostic criteria, the PSCI prevalence was lower in the fish-rich diet group (P

The excessive carbon emissions not only intensify the global climate change, but also seriously restrict the sustainable development of social economy. However, improving industrial carbon emissions efficiency is the most directly effective way to reduce emissions. Therefore, accurate measurement and analysis of carbon emissions efficiency and evolution characteristics of China's industrial system is the basis for China to improve carbon emissions efficiency. Based on this, we adopted energy consumption method and input-output method to calculate and analyze the industrial carbon emissions efficiency and evolution characteristics of China from 2002 to 2015. The results show that (1) If carbon emissions from cement production are ignored and only energy-related carbon emissions are considered, the calculation results of carbon emissions efficiency of heavy industry will be overestimated about 30%. (2) Compared with 2002, China's industrial carbon emissions efficiency increased by about twice in 2015. Specifically, the optimization of carbon emissions efficiency in agriculture, construction, light industry and service industry is very obvious, which has increased by 5.65, 5.00, 4.69 and 4.68 times respectively; The optimization of carbon emissions efficiency in power sector, heavy industry, transportation and chemical industry was obvious, which increased by 2.55, 2.01, 1.86 and 1.47 times respectively; The carbon emissions efficiency of the fossil energy sector has decreased by 0.36 times. (3) The carbon emissions efficiency of various industries has significant differences. Among them, agriculture, service industry, light industry and construction industry are generally industries with higher carbon emissions efficiency, while power sector, fossil energy sector, transportation industry, chemical industry and heavy industry are generally industries with lower carbon emissions efficiency, especially power and fossil energy sectors. Based on these, this paper provides policy implications and scientific evidence for accurately improving carbon emissions efficiency from the perspective of carbon emissions efficiency.

Abstract Background This investigation was arranged to elucidate whether single nucleotide polymorphisms (SNPs) of lncRNA UCA1 was implicated in elevating colorectal cancer (CRC) risk by interacting with environmental exposures. Methods LncRNASNP database was firstly adopted to predict SNPs that possibly affected binding of UCA1 with miRNAs and then the interactive effect of SNPs and environmental exposure on CRC risk was evaluated by recurring to type 2 gene-environment interactions (GEI) model. Besides, MTT assay, colony formation assay, transwell assay and wound healing assay were performed to assess the activity of CRC cell lines which carried distinct genotypes of specific SNPs. The impact of nicotine on activity of CRC cells was also appraised. Results SNP rs12982687 of UCA1 intervened in the binding capacity of UCA1 with several miRNAs, especially miR-873-5p. MiRNAs regulated by UCA1, as predicted by mirPath software, shared genes that were enriched in HIF1 signaling pathway. Moreover, homozygote TT of rs12982687 reduced CRC risk among smokers, and CRC cells that carried rs12982687 (CC) displayed strong migration and invasion. By contrast, miR-873-5p mimic, which reduced UCA1 expression, delayed metastasis of CRC cells (all P

In an investigation of a listeriosis outbreak in Ontario, Canada, during November 2015–June 2016, pasteurized chocolate milk was identified as the source. Because listeriosis outbreaks associated with pasteurized milk are rare in North America, these findings highlight that dairy products can be contaminated after pasteurization.

Using serial block-face scanning electron microscopy, we report on the internal 3D structures of the brown planthopper, Nilaparvata lugens (Hemiptera: Delphacidae) at nanometer resolution for the first time. Within the reconstructed organs and tissues, we found many novel and fascinating internal structures in the planthopper such as naturally occurring three four-way rings connecting adjacent spiracles to facilitate efficient gas exchange, and fungal endosymbionts in a single huge insect cell occupying 22% of the abdomen volume to enable the insect to live on plant sap. To understand the muscle and stylet movement during phloem sap-sucking, the cephalic skeleton and muscles were reconstructed in feeding nymphs. The results revealed an unexpected contraction of the protractors of the stylets and suggested a novel feeding model for the phloem sap-sucking.

Background: Energy intake and nutritional status influences a patient’s recovery from major abdominal surgery. The aim of this study is to explore and validate the clinical feasibility of an inflection-point nutrition strategy for personalized nutrition in gastric cancer patients after surgery. Methods: We conducted a prospective cohort study from a single tertiary referral hospital. Patients diagnosed with gastric cancer who met the inclusion criteria were included in this study. We collected the demographic and clinic pathological characteristics of included patients. Patients were divided into a formular nutrition (FN) and inflection-point nutrition (IPN) group. We monitored the perioperative dynamics of the oral mucosal epithelia cell apoptosis rate. Predictive factors for inflection phenomenon were investigated in univariate and multivariate analysis. Results: A total of 53 gastric cancer patients were included. A total of 30 (56.6%) patients showed the inflection phenomenon, with 9 (34.6%) patients in the FN group and 21 (77.8%) patients in the IPN group, respectively. We found that patients with the inflection phenomenon had a shorter duration of hospital stay compared to patients without the inflection phenomenon (p = 0.04). In multivariate analysis, independent predictive factors for inflection phenomenon were age (p = 0.015), operation time ≤ 300 min (p = 0.012), and average energy intake ≥ 25 Kcal/kg/day (p = 0.038). Conclusions: Our findings for the first time revealed that the oral epithelial cell apoptosis rate can promptly reflect the patients’ perioperative nutrition needs. Meanwhile, we developing a novel and feasible nutrition therapy guided by the oral epithelial cell apoptosis rate is novel in gastric cancer patients that have undergone laparoscopic gastrectomy.

Heat stress is an increasing threat to rice production worldwide. To investigate the mechanisms of heat tolerance in hybrid rice and their contributions to rice heterosis, we compared the transcriptome of the hybrid rice II YOU 838 (II8) with the transcriptomes of its parents Fu Hui 838 (F8) and II-32A (II3) after heat stress at 42 °C for 0 h, 24 h, 72 h and 120 h. We also performed a proteomic analysis in II8 after heat stress at 42 °C for 24 h. The transcriptome data revealed time-dependent gene expression patterns under the heat stress conditions, and the heat stress response of II8 was greatly different from those of its parents. Gene ontology analysis of the differentially expressed genes that were clustered using k-means clustering showed that most of the up-regulated genes were involved in responses to stimuli, cell communication, and metabolic and transcription factor activities, whereas the down-regulated genes were enriched in photosynthesis and signal transduction. Moreover, 35 unique differentially abundant proteins, including a basic helix-loop-helix transcription factor (bHLH96), calmodulin-binding transcription activator, heat shock protein (Hsp70), and chaperonin 60 (CPN60), were detected in the proteomic analysis of II8 under heat stress. The co-regulatory analysis revealed novel genes and pathways involved in heat tolerance, namely, ferredoxin-NADP reductase, peroxidases, mitogen-activated protein kinase kinase kinase, and heat shock factor (HSF)–Hsp network. Members of the Hsp and HSF families had over-dominant expression patterns in the hybrid compared with its parents, to help maintain the higher photosynthesis and antioxidant defense systems in the hybrid. Our study suggests that the complex HSF–Hsp regulatory network contribute to the heat tolerance of the hybrid rice.

The estrogen-signalling pathway is critical for normal follicular development; however, little is known about its importance during in vitro maturation (IVM) in large animals, particularly yaks (Bos grunniens). Through the present study, we aimed to determine the mechanisms underlying estrogen involvement in cumulus expansion and the subsequent development of cumulus-oocyte complexes (COCs). COCs were cultured in the maturation medium supplemented with different concentrations (10−6–10−3 mM) of 17β-estradiol (E2) or its receptor antagonist, fulvestrant, and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and western blot were performed to determine the expression of cumulus-expansion related factors and oocyte-secreted factors (OSFs). The cumulus expansion of COCs was observed using an inverted microscope, and COCs developmental ability were judged by the evaluation of cleavage and blastulation rates per inseminated oocytes by IVF, and the number of cells in the blastocyst. Cumulus expansion increased with 10−6–10−3 mM E2, but decreased with fulvestrant. HAS2, PTGS2, PTX3 and OSFs expression increased in the 10−6–10−3 mM E2 groups. Significantly higher cleavage and blastocyst rates were observed in the 10−4 mM E2 group than in the fulvestrant and 0 mM E2 groups. Moreover, in the 10−4 mM group, blastocysts at 7 days had higher cell counts than the other groups. In conclusion, the increase in cumulus expansion and subsequent oocyte development after the addition of E2 to IVM medium may have resulted from increased cumulus-expansion-related factor expression and OSF levels.

Purpose To study the effect of STN-DBS on balance performance of Parkinson's disease. Method 16 idiopathic PD patients treated with bilateral STN-DBS (DBS Group) and 20 PD patients treated with Levodopa (Medicine group) were included in the study. Clinical material including Levodopa Equivalent Daily Dose (LEDD, mg/day), life quality (PDQ-39) were collected. For DBS group and Medicine group, The motor disability (Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale Ⅲ, MDS-UPDRSIII) and balance performance (MDS-UPDRS 3.12, Berg Balance Scale BBS) and the Limits of Stability (LoS) (target acquisition percentage, trunk swing angle standard deviation, time) in state of Med-Off/Med-On at preoperation, postoperation, 6 months postoperation and 12 months postoperation were evaluated. Repeated ANOVA was used to analyze the effect of STN-DBS on balance performance. Result The Clinical material (age, gender, duration, LEDD preoperation, PDQ39), motor disability (Med-on/Med-Off), balance performance (Med-on/Med-Off) and LoS preoperation had no differences in DBS-group and Medical-group (P>0.05). During the follow up, LEDD, PDQ39, Motor disability (MDS-UPDRSIII), balance performance (MDS-UPDRS 3.12, BBS) in Medicine-group had no significant changes in both Med-Off and Med-On. For DBS-group, immediately improvement of motor disability (MDS-UPDRSIII), LoS (target acquisition percentage, trunk swing angle standard deviation, time) and LEDD were observed postoperation (P

Background: Despite recent advances that have improved the pregnancy success rates that can be achieved via in vitro fertilization (IVF) therapy, it is not yet clear which blastocyst morphological parameters best predict the outcomes of single blastocyst transfer. In addition, most of the previous studies did not exclude the effect of embryo aneuploidy on blastocysts transfer. Thus, the present study investigated the predictive value of various parameters on the pregnancy outcomes achieved via the transfer of frozen euploid blastocysts. Methods: The study retrospectively analyzed 914 single euploid blastocyst transfer cycles that were performed at the Peking University Third Hospital Reproductive Medical Center between June 2011 and May 2016. The expansion, trophectoderm (TE), and inner cell mass (ICM) quality of the blastocysts were assessed based on blastocyst parameters, and used to differentiate between “excellent”, “good”, “average”, and “poor”-quality embryos. The relationship between these embryo grades and the achieved pregnancy outcomes was then analyzed via the Chi-square and logistic regression tests. Results: For embryo grades of excellent, good, average and poor, the clinical pregnancy rates were 65.0%, 59.3%, 50.3% and 33.3%, respectively; and the live-birth rates were 50.0%, 49.7%, 42.3% and 25.0%, respectively. Both the clinical pregnancy rate (χ2 = 21.28, P = 0.001) and live-birth rate (χ2 = 13.50, P < 0.001) increased with the overall blastocyst grade. Both rates were significantly higher after the transfer of a blastocyst that exhibited either an A-grade or B-grade TE, and similarly, an A-grade ICM, than after the transfer of a blastocyst that exhibited a C-grade TE and/or ICM. The degree of blastocyst expansion had no apparent effect on the clinical pregnancy or live-birth rate. All odds ratio were adjusted for patient age, body mass index, length (years) of infertility history, and infertility type. Conclusions: A higher overall euploid blastocyst quality is shown to correlate most strongly with optimal pregnancy outcomes. The study thus supports the use of the described TE and ICM morphological grades to augment current embryo selection criteria.

Background: Although many previous studies have confirmed that perioperative blood transfusion is associated with poor outcomes after liver transplantation (LT), few studies described the influence of single-donor platelet apheresis transfusion in living donor LT (LDLT). This study aimed to assess the effect of blood products on outcomes for LDLT recipients, focusing on apheresis platelets. Methods: This retrospective study included 126 recipients who underwent their first adult-to-adult LDLT. Twenty-four variables including consumption of blood products of 126 LDLT recipients were assessed for their link to short-term outcomes and overall survival. Kaplan-Meier survival curve and the log-rank test were used for recipient survival analysis. A multivariate Cox proportional-hazard model and a propensity score analysis were applied to adjust confounders after potential risk factors were identified by a univariate Cox analysis. Results: Patients who received apheresis platelet transfusion had a lower 90-day cumulative survival (78.9% vs. 94.2%, P = 0.009), but had no significant difference in overall survival in the Cox model, compared with those without apheresis platelet transfusion. Units of apheresis platelet transfusion (hazard ratio [HR] = 3.103, 95% confidence interval [CI]: 1.720–5.600, P < 0.001) and preoperative platelet count (HR = 0.170, 95% CI: 0.040–0.730, P = 0.017) impacted 90-day survival independently. Multivariate Cox regression analysis also found that units of red blood cell (RBC) transfusion (HR = 1.036, 95% CI: 1.006–1.067, P = 0.018), recipient's age (HR = 1.045, 95% CI: 1.005–1.086, P = 0.025), and ABO blood group comparison (HR = 2.990, 95% CI: 1.341–6.669, P = 0.007) were independent risk factors for overall survival after LDLT. Conclusions: This study suggested that apheresis platelets were only associated with early mortality but had no impact on overall survival in LDLT. Units of RBC, recipient's age, and ABO group comparison were independent predictors of long-term outcomes.

Background: After the two-child policy is fully implemented, new challenges regarding pregnancy management and the treatment of pregnancy complications will arise. The aim of this study was to analyze the characteristics of pregnancy and delivery before and after the implementation of the two-child policy to make suggestions on the quality assurance of the new era of obstetrics. Methods: In total, 5895 cases of pregnant women who delivered from April 2016 to March 2017 in Peking University Third Hospital served as the study group and 5103 cases of pregnant women who delivered from January to December 2015 served as the control group. The characteristics of pregnancy and delivery were retrospectively analyzed. Results: In the study group, the percentage of pregnant women who were older (over 40 years) (3.6% vs. 2.2%), were multipara (30.3% vs. 17.0%), received irregular prenatal care (1.5% vs. 0.9%), were transferred for treatment from a subordinate hospital (4.4% vs. 2.8%), and were not residents of Beijing (3.8% vs. 2.2%), were significantly increased compared with the control group (P < 0.05). In the study group, the rate of a hypertensive disorder complicating pregnancy (6.4% vs. 5.0%), gestational diabetes mellitus (25.3% vs. 23.1%), dangerous placenta previa (3.0% vs. 2.3%), placental implantation (2.4% vs. 1.8%), and severe postpartum hemorrhage (2.8% vs. 1.9%) was significantly increased compared with the control group (P < 0.05). In the study group, the cesarean section rate during primipara was significantly reduced compared with the control group (42.0% vs. 44.2%). However, the rate during multipara was significantly increased compared with the control group (P < 0.05). Indications for cesarean section in the study group as well as the percentages of scared uterus and placenta previa were significantly increased compared with the control group (P < 0.05). Conclusions: According to the current situation, better methods are needed to strengthen pregnancy and delivery management, reduce the rate of cesarean section, and ensure a positive outcome for mothers and babies.

Background: One-lung ventilation (OLV) is a common ventilation technology during thoracic surgery that can cause serious clinical problems. We aimed to conduct a meta-analysis to compare oxygenation and intrapulmonary shunt during OLV in adults undergoing thoracic surgery with dexmedetomidine (Dex) versus placebo to assess the influence and safety of using Dex. Methods: Randomized controlled trials comparing lung protection in patients who underwent thoracic surgery with Dex or a placebo were retrieved from PubMed, EMBASE, MEDLINE, Cochrane Library, and China CNKI database. The following information was extracted from the paper: arterial oxygen partial pressure (PaO2), PaO2/inspired oxygen concentration (PaO2/FiO2, oxygenation index [OI]), intrapulmonary shunt (calculated as Qs/Qt), mean arterial pressure (MAP), heart rate (HR), tumor necrosis factor-α (TNF-α), interleukin (IL)-6, superoxide dismutase (SOD), and malondialdehyde (MDA). Results: Fourteen randomized controlled trials were included containing a total of 625 patients. Compared with placebo group, Dex significantly increased PaO2/FiO2(standard mean difference [SMD] = 0.98, 95% confidence interval [CI] [0.72, 1.23], P < 0.00001). Besides, Qs/Qt (SMD= −1.22, 95% CI [−2.20, −0.23], P = 0.020), HR (SMD= −0.69, 95% CI [−1.20, 0.17], P = 0.009), MAP (SMD= −0.44, 95% CI [−0.84, 0.04], P = 0.030), the concentrations of TNF-α (SMD = −1.55, 95% CI [−2.16, −0.95], P

In river-lake systems, sediment and water column are two distinct habitats harboring different bacterial communities which play a crucial role in biogeochemical processes. In this study, we employed Phylogenetic Investigation of Communities by Reconstruction of Unobserved States to assess the potential functions and functional redundancy of the bacterial communities in sediment and water in a eutrophic river-lake ecosystem, Poyang Lake in China. Bacterial communities in sediment and water had distinct potential functions of carbon, nitrogen, and sulfur metabolisms as well as phosphorus cycle, while the differences between rivers and the lake were inconspicuous. Bacterial communities in sediment had a higher relative abundance of genes associated with carbohydrate metabolism, carbon fixation pathways in prokaryotes, methane metabolism, anammox, nitrogen fixation, and dissimilatory sulfate reduction than that of water column. Bacterial communities in water column were higher in lipid metabolism, assimilatory nitrate reduction, dissimilatory nitrate reduction, phosphonate degradation, and assimilatory sulfate reduction than that of sediment bacterial communities. Furthermore, the variations in functional composition were closely associated to the variations in taxonomic composition in both habitats. In general, the bacterial communities in water column had a lower functional redundancy than in sediment. Moreover, comparing to the overall functions, bacterial communities had a lower functional redundancy of nitrogen metabolism and phosphorus cycle in water column and lower functional redundancy of nitrogen metabolism in sediment. Distance-based redundancy analysis and mantel test revealed close correlations between nutrient factors and functional compositions. The results suggested that bacterial communities in this eutrophic river-lake system of Poyang Lake were vulnerable to nutrient perturbations, especially the bacterial communities in water column. The results enriched our understanding of the bacterial communities and major biogeochemical processes in the eutrophic river-lake ecosystems.

Objective To evaluate the effect of the comprehensive intervention of the oral health education for children aged 6 to 12 years.Methods The oral health knowledge questionnaire was used to evaluatethe children′s awareness about oral health and the correct rate of tooth-brushing before and after 12-month comprehensive intervention. Two organizational forms about pit and fissure sealant were adopted. In city school, students were brought by their parents to the hospital to do pit and fissure sealant, while in rural school, hospital medical team went to schools to do pit and fissure sealant for the students. Compare the sealants retention rate in 12-month follow-up between two forms. The total sealants retention rate among 6-month, 12-month and 24-month follow-up were compared.Results Before and after oral health education guidance, the rate of children′s oral health awareness was 68% and 96%, and the correct rate of tooth-brushing was 64% and 92% respectively (P

BACKGROUND:The aim of this study was to summarize and discuss the similarities and differences in inflammatory biomarkers in postoperative delirium (POD) and cognitive dysfunction (POCD). METHODS:A systematic retrieval of literature up to June 2017 in PubMed, Embase, the Cochrane Library, the China National Knowledge Infrastructure database, and the Wanfang database was conducted. Extracted data were analyzed with STATA (version 14). The standardized mean difference (SMD) and the 95% confidence interval (95% CI) of each indicator were calculated using a random effect model. We also performed tests of heterogeneity, sensitivity analysis, assessments of bias, and meta-regression in this meta-analysis. RESULTS:A total of 54 observational studies were included. By meta-analysis we found significantly increased C-reactive protein (CRP) (9 studies, SMD 0.883, 95% CI 0.130 to 1.637, P = 0.022 in POD; 10 studies, SMD -0.133, 95% CI -0.512 to 0.246, P = 0.429 in POCD) and interleukin (IL)-6 (7 studies, SMD 0.386, 95% CI 0.054 to 0.717, P = 0.022 in POD; 16 studies, SMD 0.089, 95% CI -0.133 to 0.311, P = 0.433 in POCD) concentrations in both POD and POCD patients. We also found that the SMDs of CRP and IL-6 from POCD patients were positively correlated with surgery type in the meta-regression (CRP: Coefficient = 1.555365, P = 0.001, 10 studies; IL-6: Coefficient = -0.6455521, P = 0.086, 16 studies). CONCLUSION:Available evidence from medium-to-high quality observational studies suggests that POD and POCD are indeed correlated with the concentration of peripheral inflammatory markers. Some of these markers, such as CRP and IL-6, play roles in both POD and POCD, while others are specific to either one of them.

The spatial location of proteins in living cells can be critical for their function. For example, the E. coli chemotaxis machinery is localized to the cell poles. Here we describe the polar localization of the serine chemoreceptor Tsr using a strain synthesizing a fluorescent Tsr-Venus fusion at a low level from a single-copy chromosomal construct. Using photobleaching and imaging during recovery by new synthesis, we observed distinct asymmetry between a bright (old) pole and a dim (new) pole. The old pole was shown to be a more stable cluster and to recover after photobleaching faster, which is consistent with the hypothesis that newly synthesized Tsr proteins are inserted directly at or near the old pole. The new pole was shown to be a less stable cluster and to exchange proteins freely with highly mobile Tsr-Venus proteins diffusing in the membrane. We propose that the new pole arises from molecules escaping from the old pole and diffusing to the new pole where a more stable cluster forms over time. Our localization imaging data support a model in which a nascent new pole forms prior to stable cluster formation.

With increasing awareness of reduction of energy and CO2 footprint, more waste is considered recyclable for generating value-added products. Here we reported the negatively-valued iron mud, a waste from groundwater treatment plant, was successfully converted into magnetic adsorbent. Comparing with the conventional calcination method under the high temperature and pressure, the synthesis of the magnetic particles (MPs) by Fe2+/Fe3+ coprecipitation was conducted at environment-friendly condition using ascorbic acid (H2A) as reduction reagent and nitric acid (or acid wastewater) as leaching solution. The MPs with major component of Fe3O4 were synthesized at the molar ratio (called ratio subsequently) of H2A to Fe3+ of iron mud ≥ 0.1; while amorphous ferrihydrite phase was formed at the ratio ≤ 0.05, which were confirmed by vibrating sample magnetometer (VSM), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). With the ratio increased, the crystalline size and the crystallization degree of MPs increased, and thus the Brunauer-Emmett-Teller (BET) surface and the cation-exchange capacity (CEC) decreased. MPs-3 prepared with H2A to Fe3+ ratio of 0.1 demonstrated the highest methylene blue (MB) adsorption of 87.3 mg/g and good magnetic response. The adsorption of MB onto MPs agreed well with the non-linear Langmuir isotherm model and the pseudo-second-order model. Pilot-scale experiment showed that 99% of MB was removed by adding 10 g/L of MPs-3. After five adsorption-desorption cycles, MPs-3 still showed 62% removal efficiency for MB adsorption. When nitric acid was replaced by acid wastewater from a propylene plant, the synthesized MPs-3w showed 3.7 emu/g of saturation magnetization (Ms) and 56.7 mg/g of MB adsorption capacity, 2.8 times of the widely used commercial adsorbent of granular active carbon (GAC). The major mechanism of MPs adsorption for MB was electrostatic attraction and cation exchange. This study synthesized a magnetic adsorbent from the negatively-valued iron mud waste by using an environment-friendly coprecipitation method, which had a potential for treatment of dye wastewater.

[This corrects the article DOI: 10.1371/journal.pone.0191749.].

Mammalian cell culture is foundational to biomedical research, and the reproducibility of research findings across the sciences is drawing increasing attention. While many components contribute to reproducibility, the reporting of factors that impact oxygen delivery in the general biomedical literature has the potential for both significant impact, and immediate improvement. The relationship between the oxygen consumption rate of cells and the diffusive delivery of oxygen through the overlying medium layer means parameters such as medium depth and cell type can cause significant differences in oxygenation for cultures nominally maintained under the same conditions. While oxygenation levels are widely understood to significantly impact the phenotype of cultured cells in the abstract, in practise the importance of the above parameters does not appear to be well recognized in the non-specialist research community. On analyzing two hundred articles from high-impact journals we find a large majority missing at least one key piece of information necessary to ensure consistency in replication. We propose that explicitly reporting these values should be a requirement for publication.

Aim To evaluate the effects of sodium-glucose co-transporter 2 (SGLT2) inhibition on renal function and albuminuria in patients with type 2 diabetes. Methods We conducted systematic searches of PubMed, Embase and Cochrane Central Register of Controlled Trials up to June 2016 and included randomized controlled trials of SGLT2 inhibitors in adult type 2 diabetic patients reporting estimated glomerular filtration rate (eGFR) and/or urine albumin/creatinine ratio (ACR) changes. Data were synthesized using the random-effects model. Results Forty-seven studies with 22,843 participants were included. SGLT2 inhibition was not associated with a significant change in eGFR in general (weighted mean difference (WMD), −0.33 ml/min per 1.73 m2, 95% CI [−0.90 to 0.23]) or in patients with chronic kidney disease (CKD) (WMD −0.78 ml/min per 1.73 m2, 95% CI [−2.52 to 0.97]). SGLT2 inhibition was associated with eGFR reduction in short-term trials (WMD −0.98 ml/min per 1.73 m2, 95% CI [−1.42 to −0.54]), and with eGFR preservation in long-term trials (WMD 2.01 ml/min per 1.73 m2, 95% CI [0.86 to 3.16]). Urine ACR reduction after SGLT2 inhibition was not statistically significant in type 2 diabetic patients in general (WMD −7.24 mg/g, 95% CI [−15.54 to 1.06]), but was significant in patients with CKD (WMD −107.35 mg/g, 95% CI [−192.53 to −22.18]). Conclusions SGLT2 inhibition was not associated with significant changes in eGFR in patients with type 2 diabetes, likely resulting from a mixture of an initial reduction of eGFR and long-term renal function preservation. SGLT2 inhibition was associated with statistically significant albuminuria reduction in type 2 diabetic patients with CKD.

A simple residue analytical method based on the QuEChERS approach and high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) detection was developed for the analysis of fipronil and its three metabolites in cottonseed, cotton plant and soil. The average recoveries of four test compounds from all three matrices were 78.6-108.9% at the level of 0.005 to 0.5 mg/kg, with an RSD in the range of 0.6 to 13.7%. The limit of quantification (LOQ) of the four test compounds ranged from 0.005 to 0.01 mg/kg. The results of the residual dynamics experiments showed that fipronil dissipated rapidly in cotton plants and soil and that oxidation and photolysis were the main degradation pathways. Moreover, the bi-exponential models demonstrated a good fit of the measured data for fipronil in cotton plants and soil, with R2 in the range of 0.8989 to 0.9989. Furthermore, a total of 40 samples of cottonseed from Shandong Province were analyzed, and all of the samples were free from the four test compound residues.

4'-Hydroxywogonin (4'-HW), a flavonoid, has been isolated from various plants and shown to inhibit NO production in macrophages. However, the molecular mechanisms and its in vivo activity have not been determined. Our study aimed to investigate the mechanisms underlying the anti-inflammatory effects of 4'-HW in vitro and in vivo. We showed that 4'-HW potently reduced the expression levels of COX-2 and iNOS as well as their products, prostaglandin E2 (PGE2) and nitric oxide (NO) respectively, in LPS-stimulated RAW 264.7 macrophages. 4'-HW also suppressed LPS-induced pro-inflammatory cytokines at mRNA and protein levels. Moreover, 4'-HW blocked the interaction of TAK1 and TAB1 in LPS-stimulated RAW 264.7 macrophages, resulting in an inhibition of the TAK1/IKK/NF-κB signaling pathway. Furthermore, 4'-HW also reduced the phosphorylation of MAPKs and PI3/Akt signaling pathways in LPS-stimulated RAW 264.7 macrophages. 4'-HW was also significantly decreased the intracellular reactive oxygen species (ROS) level. The effect of 4'-HW was confirmed in vivo. 4'-HW exhibited potent protective effect against LPS-induced ALI in mice. These findings indicate that 4'-HW suppresses the LPS-induced response in vitro and in vivo. It is likely that the inhibition of the TAK1/IKK/NF-κB, MAPKs and PI3/AKT signaling pathways contribute to the anti-inflammatory effects of 4'-HW. Our study suggests that 4'-HW may be an important functional constituent in the plants and has the potential value to be developed as a novel anti-inflammatory agent.

BACKGROUND AND OBJECTIVES: Off-pump coronary artery bypass grafting (OPCAB) is a popular treatment for patients with ischemic heart disease, especially for high-risk patients. However, whether OPCAB can lead to better clinical outcomes than on-pump coronary artery bypass grafting (ONCAB) in patients with enlarged ventricles remains controversial. This prospective randomized study was designed to characterize comparison of early clinical outcome and mid-term follow-up following ONCAB versus OPCAB in patients with triple-vessel disease and enlarged ventricles. DESIGN AND SETTINGS: Prospective randomized trial of patients treated at The First Affiliated Hospital, China Medical University, over a 3-year period (2007–2010). METHODS: A total of 102 patients with triple-vessel disease and enlarged ventricles (end-diastolic dimension ≥6.0 cm) were randomized to OPCAB or ONCAB between July 2007 and December 2010. The in-hospital outcomes were analyzed. The study included a mid-term follow-up, with a mean follow-up time of 49.40 (12.88 months). RESULTS: No significant differences were recorded in the baseline clinical characteristics of ONCAB and OPCAB groups. A statistical difference was found between the two groups at the time of extubation, intensive care unit stay, hospital stay, blood requirements, incidence of intra-aortic balloon pump support, pulmonary complications, stroke, reoperation for bleeding, and inotropic requirements >24 hours (P.05). The left ventricular end-diastolic dimension was significantly smaller at 6 months' follow-up in the 2 groups than it was before operation (

Viral replicase recruitment and long-range RNA interactions are essential for RNA virus replication, yet the mechanism of their interplay remains elusive. Flaviviruses include numerous important human pathogens, e.g., dengue virus (DENV) and Zika virus (ZIKV). Here, we revealed a highly conserved, conformation-tunable cis-acting element named 5′-UAR-flanking stem (UFS) in the flavivirus genomic 5′ terminus. We demonstrated that the UFS was critical for efficient NS5 recruitment and viral RNA synthesis in different flaviviruses. Interestingly, stabilization of the DENV UFS impaired both genome cyclization and vRNA replication. Moreover, the UFS unwound in response to genome cyclization, leading to the decreased affinity of NS5 for the viral 5′ end. Thus, we propose that the UFS is switched by genome cyclization to regulate dynamic RdRp binding for vRNA replication. This study demonstrates that the UFS enables communication between flavivirus genome cyclization and RdRp recruitment, highlighting the presence of switch-like mechanisms among RNA viruses.

CLCA2 is a p53-, p63-inducible transmembrane protein that is frequently downregulated in breast cancer. It is induced during differentiation of human mammary epithelial cells, and its knockdown causes epithelial-to-mesenchymal transition (EMT). To determine how CLCA2 promotes epithelial differentiation, we searched for interactors using membrane dihybrid screening. We discovered a strong interaction with the cell junctional protein EVA1 (Epithelial V-like Antigen 1) and confirmed it by co-immunoprecipitation. Like CLCA2, EVA1 is a type I transmembrane protein that is regulated by p53 and p63. It is thought to mediate homophilic cell-cell adhesion in diverse epithelial tissues. We found that EVA1 is frequently downregulated in breast tumors and breast cancer cell lines, especially those of mesenchymal phenotype. Moreover, knockdown of EVA1 in immortalized human mammary epithelial cells (HMEC) caused EMT, implying that EVA1 is essential for epithelial differentiation. Both EVA1 and CLCA2 co-localized with E-cadherin at cell-cell junctions. The interacting domains were delimited by deletion analysis, revealing the site of interaction to be the transmembrane segment (TMS). The primary sequence of the CLCA2 TMS was found to be conserved in CLCA2 orthologs throughout mammals, suggesting that its interaction with EVA1 co-evolved with the mammary gland. A screen for other junctional interactors revealed that CLCA2 was involved in two different complexes, one with EVA1 and ZO-1, the other with beta catenin. Overexpression of CLCA2 caused downregulation of beta catenin and beta catenin-activated genes. Thus, CLCA2 links a junctional adhesion molecule to cytosolic signaling proteins that modulate proliferation and differentiation. These results may explain how attenuation of CLCA2 causes EMT and why CLCA2 and EVA1 are frequently downregulated in metastatic breast cancer cell lines.

Berberine (BBR) has been shown to exhibit protective effects against diabetes and dyslipidemia. Previous studies have indicated that BBR modulates lipid metabolism and inhibits hepatic gluconeogensis by decreasing expression of Hepatocyte Nuclear Factor-4α (HNF-4α). However, the mechanism involved in this process was unknown. In the current study, we examined the mechanism of how BBR attenuates hepatic gluconeogenesis and the lipid metabolism alterations observed in type 2 diabetic (T2D) mice and in palmitate (PA)-incubated HepG2 cells. Treatment with BBR for 4 weeks improve all biochemical parameters compared to T2D mice. Treatment of T2D mice for 4 weeks or treatment of PA-incubated HepG2 cells for 24 h with BBR decreased expression of HNF-4α and the microRNA miR122, the key gluconeogenesis enzymes Phosphoenolpyruvate carboxykinase (PEPCK) and Glucose-6-phosphatase (G6Pase) and the key lipid metabolism proteins Sterol response element binding protein-1 (SREBP-1), Fatty acid synthase-1 (FAS-1) and Acetyl-Coenzyme A carboxylase (ACCα) and increased Carnitine palmitoyltransferase-1(CPT-1) compared to T2D mice or PA-incubated HepG2 cells. Expression of HNF-4α in HepG2 cells increased expression of gluconeogenic and lipid metabolism enzymes and BBR treatment or knock down of miR122 attenuated the effect of HNF-4α expression. In contrast, BBR treatment did not alter expression of gluconeogenic and lipid metabolism enzymes in HepG2 cells with knockdown of HNF-4α. In addition, miR122 mimic increased expression of gluconeogenic and lipid metabolism enzymes in HepG2 cells with knockdown of HNF-4α. These data indicate that miR122 is a critical regulator in the downstream pathway of HNF-4α in the regulation of hepatic gluconeogenesis and lipid metabolism in HepG2 cells. The effect of BBR on hepatic gluconeogenesis and lipid metabolism is mediated through HNF-4α and is regulated downstream of miR122. Our data provide new evidence to support HNF-4α and miR122 regulated hepatic gluconeogenesis and lipid metabolism as promising therapeutic targets for the treatment of T2D.

Investigations on the relationship of toxicities between species play an important role in the understanding of toxic mechanisms to environmental organisms. In this paper, the toxicity data of 949 chemicals to fish and 1470 chemicals to V. fischeri were used to investigate the modes of action (MOAs) between species. The results show that although there is a positive interspecies correlation, the relationship is poor. Analysis on the excess toxicity calculated from toxic ratios (TR) shows that many chemicals have close toxicities and share the same MOAs between the two species. Linear relationships between the toxicities and octanol/water partition coefficient (log KOW) for baseline and less inert compounds indicate that the internal critical concentrations (CBRs) approach a constant both to fish and V. fischeri for neutral hydrophobic compounds. These compounds share the same toxic mechanisms and bio-uptake processes between species. On the other hand, some hydrophilic compounds exhibit different toxic effects with greatly different log TR values between V. fischeri and fish species. These hydrophilic compounds were identified as reactive MOAs to V. fischeri, but not to fish. The interspecies correlation is improved by adding a hydrophobic descriptor into the correlation equation. This indicates that the differences in the toxic ratios between fish and V. fischeri for these hydrophilic compounds can be partly attributed to the differences of bioconcentration between the two species, rather than the differences of reactivity with the target macromolecules. These hydrophilic compounds may more easily pass through the cell membrane of V. fischeri than the gill and skin of fish, react with the target macromolecules and exhibit excess toxicity. The compounds with log KOW > 7 exhibiting very low toxicity (log TR < -1) to both species indicate that the bioconcentration potential of a chemical plays a very important role in the identification of excess toxicity and MOAs.

In preparation for the introduction of human papillomavirus (HPV) vaccine, we investigated awareness and knowledge of HPV/HPV vaccine and potential acceptability to HPV vaccine among mothers with a teenage daughter in Weihai, Shandong, China. A cross-sectional survey was conducted in 2013 with a sample of 1850 mothers who had a daughter (aged 9-17 years) attending primary, junior and senior high schools. In the final sample (N = 1578, response rate 85.30%), awareness of HPV was reported by 305 (19.32%) mothers. Awareness varied significantly by daughter's age (P

The toxic effects of silica nanoparticles (SiNPs) are raising concerns due to its widely applications in biomedicine. However, current information about the epigenetic toxicity of SiNPs is insufficient. In this study, the epigenetic regulation of low-dose exposure to SiNPs was evaluated in human bronchial epithelial BEAS-2B cells over 30 passages. Cell viability was decreased in a dose- and passage-dependent manner. The apoptotic rate, the expression of caspase-9 and caspase-3, were significantly increased induced by SiNPs. HumanMethylation450 BeadChip analysis identified that the PI3K/Akt as the primary apoptosis-related pathway among the 25 significant altered processes. The differentially methylated sites of PI3K/Akt pathway involved 32 differential genes promoters, in which the CREB3L1 and Bcl-2 were significant hypermethylated. The methyltransferase inhibitor, 5-aza, further verified that the DNA hypermethylation status of CREB3L1 and Bcl-2 were associated with downregulation of their mRNA levels. In addition, mitochondrial-mediated apoptosis was triggered by SiNPs via the downregulation of PI3K/Akt/CREB/Bcl-2 signaling pathway. Our findings suggest that long-term low-dose exposure to SiNPs could lead to epigenetic alterations.

Staphylococcus aureus remains the major cause of morbidity of bovine mastitis worldwide leading to massive economic losses. Cefquinome is a fourth generation cephalosporin, which preserves susceptibility and antibacterial activity against S. aureus. This work aims to study the pharmacokinetic (PK) and pharmacodynamic (PD) modeling following intramammary administration of cefquinome against S. aureus mastitis. The mouse model of S. aureus mastitis was developed for the PK/PD experiments. The plasma PK characteristics after intramammary injection of cefquinome at various single doses of 25, 50, 100, 200, 400 μg per gland (both fourth pairs of glands: L4 and R4) were calculated using one-compartment and first-order absorption model. PD study was investigated based on twenty-one intermittent dosing regimens, of which total daily dose ranged from 25 to 4800 μg per mouse and dosage intervals included 8, 12 or 24 h. The sigmoid Emax model of inhibitory effect was employed for PK/PD modeling. The results of PK/PD integration of cefquinome against S. aureus suggested that the percentage of duration that drug concentration exceeded the minimal inhibitory concentration (%T>MIC) and the ratio of area under time-concentration curve over MIC (AUC/MIC) are important indexes to evaluate the antibacterial activity. The PK/PD parameters of %T>MIC and AUC0-24/MIC were 35.98% and 137.43 h to obtain a 1.8 logCFU/gland reduction of bacterial colony counts in vivo, against S. aureus strains with cefquinome MIC of 0.5μg/ml.

Bone pain is a common and severe symptom in cancer patients. The present study employed a mouse model of leukemia bone pain by injection K562 cells into tibia of mouse to evaluate the analgesic effects of lappacontine. Our results showed that the lappaconitine treatment at day 15, 17 and 19 could effectively reduce the spontaneous pain scoring values, restore reduced degree in the inclined-plate test induced by injection of K562 cells, as well as restore paw mechanical withdrawal threshold and paw withdrawal thermal latency induced by injection of K562 cells to the normal levels. Additionally, the molecular mechanisms of lappaconitine’s analgesic effects may be related to affect the expression levels of endogenous opioid system genes (POMC, PENK and MOR), as well as apoptosis-related genes (Xiap, Smac, Bim, NF-κB and p53). Our present results indicated that lappaconitine may become a new analgesic agent for leukemia bone pain management.

Calcium, as the most widely accepted messenger, plays an important role in plant stress responses through calcium-dependent signaling pathways. The calmodulin-like family genes (CMLs) encode Ca2+ sensors and function in signaling transduction in response to environmental stimuli. However, until now, the function of plant CML proteins, especially soybean CMLs, is largely unknown. Here, we isolated a Glycine soja CML protein GsCML27, with four conserved EF-hands domains, and identified it as a calcium-binding protein through far-UV CD spectroscopy. We further found that expression of GsCML27 was induced by bicarbonate, salt and osmotic stresses. Interestingly, ectopic expression of GsCML27 in Arabidopsis enhanced plant tolerance to bicarbonate stress, but decreased the salt and osmotic tolerance during the seed germination and early growth stages. Furthermore, we found that ectopic expression of GsCML27 decreases salt tolerance through modifying both the cellular ionic (Na+, K+) content and the osmotic stress regulation. GsCML27 ectopic expression also decreased the expression levels of osmotic stress-responsive genes. Moreover, we also showed that GsCML27 localized in the whole cell, including cytoplasm, plasma membrane and nucleus in Arabidopsis protoplasts and onion epidermal cells, and displayed high expression in roots and embryos. Together, these data present evidence that GsCML27 as a Ca2+-binding EF-hand protein plays a role in plant responses to bicarbonate, salt and osmotic stresses.

We study the numerical solution of the Greeks of Asian options. In particular, we derive a close form solution of Δ of Asian geometric option and use this analytical form as a control to numerically calculate Δ of Asian arithmetic option, which is known to have no explicit close form solution. We implement our proposed numerical method and compare the standard error with other classical variance reduction methods. Our method provides an efficient solution to the hedging strategy with Asian options.

The broad applications and mechanism explorations of traditional Chinese medicine prescriptions (TCMPs) require a clear understanding of TCMP chemical constituents. In the present study, we describe an efficient and universally applicable analytical approach based on ultra-performance liquid chromatography coupled to electrospray ionization tandem quadrupole time-of-flight mass spectrometry (UPLC-ESI-Q/TOF-MS) with the MS(E) ((E) denotes collision energy) data acquisition mode, which allowed the rapid separation and reliable determination of TCMP chemical constituents. By monitoring diagnostic ions in the high energy function of MS(E), target peaks of analogous compounds in TCMPs could be rapidly screened and identified. "Re-Du-Ning" injection (RDN), a eutherapeutic traditional Chinese medicine injection (TCMI) that has been widely used to reduce fever caused by viral infections in clinical practice, was studied as an example. In total, 90 compounds, including five new iridoids and one new sesquiterpene, were identified or tentatively characterized by accurate mass measurements within 5 ppm error. This analysis was accompanied by MS fragmentation and reference standard comparison analyses. Furthermore, the herbal sources of these compounds were unambiguously confirmed by comparing the extracted ion chromatograms (EICs) of RDN and ingredient herbal extracts. Our work provides a certain foundation for further studies of RDN. Moreover, the analytical approach developed herein has proven to be generally applicable for profiling the chemical constituents in TCMPs and other complicated mixtures.

The present study evaluated the influence of hyperandrogenism on oocyte quality using a murine PCOS model induced by dehydroepiandrosterone (DHEA) and further explored the effect of metformin treatment. Female BALB/c mice were treated with a vehicle control or DHEA (6 mg /100 g body weight) or DHEA plus metformin (50 mg /100 g body weight) for 20 consecutive days. DHEA-induced mice resembled some characters of human PCOS, such as irregular sexual cycles and polycystic ovaries. After the model validation was completed, metaphase II (MII) oocytes were retrieved and subsequent analyses of oocyte quality were performed. DHEA-treated mice yielded fewer MII oocytes, which displayed decreased mtDNA copy number, ATP content, inner mitochondrial membrane potential, excessive oxidative stress and impaired embryo development competence compared with those in control mice. Metformin treatment partially attenuated those damages, as evidenced by the increased fertilization and blastocyst rate, ATP content, GSH concentration and GSH/GSSG ratio, and decreased reactive oxygen species levels. No significant difference in normal spindle assembly was observed among the three groups. During in vitro maturation (IVM), the periods of germinal vesicle breakdown (GVBD) and the first polar body (PB1) extrusion were extended and the maturation rate of GVBD oocytes was decreased in DHEA mice compared with controls. Metformin treatment decreased the time elapsed of GVBD while had no effect on PB1 extrusion. These results indicated that excessive androgen is detrimental to oocyte quality while metformin treatment is, directly or indirectly, beneficial for oocyte quality improvement.

This study was to evaluate the usefulness of serum thymoglobulin (Tg) in adults to assess iodine status through a 5-year cohort study which was conducted in three regions with different levels of iodine intake: mild deficiency, more than adequate, and excess, from 1999 to 2004 in China. A total of 3099 subjects over 14 years old with normal serum levels of Tg in 1999 were eligible, of whom 2448 were followed in 2004. Serum levels of thyroid hormones and thyroid autoantibodies as well as urine iodine were measured, and B-mode ultrasonography of the thyroid was performed. A general linear model was performed to determine the determinant factors of serum Tg. Among subjects with mildly deficient iodine intake, those with more than adequate intake, and those with excessive intake, the baseline levels of serum Tg were substantially different (7.5μg/L, 5.9μg/L, and 6.8μg/L respectively, P

One of the major obstacles to ovarian tissue preservation is delayed angiogenesis that leads follicles lost after transplantation. The aim of the present study was to investigate the effects of bFGF and VEGF on heterotopic transplanted ovarian tissue using a mouse model.Female mice underwent bilateral ovariectomy. Ovarian tissues encapsulated by fibrin hydrogels were transplanted subcutaneously into recipient mice, in which ovarian hormonal cyclicity was absent. The fibrinogen solution was mixed with bFGF, VEGF, or a mixture of bFGF and VEGF. The grafts were recovered 21 days after transplantation. Follicle morphology and follicle numbers were observed by H&E staining. Blood vessels were observed in transplanted intra-ovarian tissue by CD31 antibody IHC staining. Daily vaginal cytology was performed to determine estrous cycle and functional restoration of transplanted ovarian tissue. Blood was collected weekly and serum FSH levels were measured with a radioimmunoassay kit. Apoptosis analysis was performed by anti-AC-3 staining and survivin mRNA expression.The number of primordial follicles and secondary follicles in the bFGF+VEGF group was significantly higher than in the control group. The vascular density in the bFGF+VEGF groups were significantly higher than in the bFGF and the VEGF groups; there was no significant difference between the bFGF and VEGF groups. Estrous cycle was earlier in the bFGF+VEGF group compared with the control group; all mice in this group restored ovarian function. Serum FSH levels in the bFGF+VEGF group were significantly lower than in the control group by day 14 post-transplantation. The AC-3-positive in control group was significantly higher compared with bFGF group and VEGF group, and in bFGF+VEGF group was significantly lower than bFGF group and VEGF group. Survivin mRNA expression in bFGF+VEGF group was significantly higher than control group.The combination of bFGF and VEGF has beneficial effects on follicle survival, angiogenesis, and resumption of estrous cycles.

To investigate potential mechanisms involving abnormal iron metabolism and related inflammation in Parkinson disease (PD) patients with probable rapid eye movement sleep behavior disorder (PRBD).Total 210 PD patients and 31 controls were consecutively recruited. PD patients were evaluated by RBD Screening Questionnaire (RBDSQ) and classified into PRBD and probable no RBD (NPRBD) groups. Demographics information were recorded and clinical symptoms were evaluated by series of rating scales. Levels of iron and related proteins and inflammatory factors in cerebrospinal fluid (CSF) and serum were detected. Comparisons among control, NPRBD and PRBD groups and correlation analyses between RBDSQ score and levels of above factors were performed.(1) The frequency of PRBD in PD patients is 31.90%. (2) PRBD group has longer disease duration, more advanced disease stage, severer motor symptoms and more non-motor symptoms than NPRBD group. (3) In CSF, levels of iron, transferrin, NO and IL-1β in PRBD group are prominently increased. RBDSQ score is positively correlated with the levels of iron, transferrin, NO and IL-1β in PD group. Iron level is positively correlated with the levels of NO and IL-1β in PD group. (4) In serum, transferrin level is prominently decreased in PRBD group. PGE2 level in PRBD group is drastically enhanced. RBDSQ score exhibits a positive correlation with PGE2 level in PD group.PRBD is common in PD patients. PRBD group has severer motor symptoms and more non-motor symptoms. Excessive iron in brain resulted from abnormal iron metabolism in central and peripheral systems is correlated with PRBD through neuroinflammation.

We studied the Japan and U.S. patent records of several decades to demonstrate the effect of collaboration on innovation. We found that statistically inventor teams slightly outperform solo inventors while company teams perform equally well as solo companies. By tracking the performance record of individual teams, we found that inventor teams' performance generally degrades with more repeat collaborations. Though company teams' performance displays strongly bursty behavior, long-term collaboration does not significantly help innovation. To systematically study the effect of repeat collaboration, we defined the repeat collaboration number of a team as the average number of collaborations over all the teammate pairs. We found that mild repeat collaboration improves the performance of Japanese inventor teams and U.S. company teams. Yet, excessive repeat collaboration does not significantly help innovation at both the inventor and company levels in both countries. To control for unobserved heterogeneity, we performed a detailed regression analysis and the results were consistent with our simple observations. The presented results revealed the intricate effect of collaboration on innovation, which may also be observed in other creative projects.

Double minute chromosomes (DMs) have important implications for cancer progression because oncogenes frequently amplified on them. We previously detected a functionally undefined gene amplified on DMs, Ribosomal L22-like1 (RPL22L1). The relationship between RPL22L1 and cancer progression is unknown. Here, RPL22L1 was characterized for its role in ovarian cancer (OC) metastasis and its underlying mechanism was examined. DNA copy number and mRNA expression of RPL22L1 in OC cells was analyzed using data obtained from The Cancer Genome Atlas and the Gene Expression Omnibus database. An immunohistochemical analysis of clinical OC specimens was performed and the relationships between expression level and clinicopathological factors were evaluated. Additionally, in vivo and in vitro assays were performed to understand the role of RPL22L1 in OC. RPL22L1 expression was higher in OC specimens than in normal tissues, and its expression level was highly positively correlated with invasion and lymph node metastasis (P < 0.05). RPL22L1 over-expression significantly enhanced intraperitoneal xenograft tumor development in nude mice and promoted invasion and migration in vitro. Additionally, RPL22L1 knockdown remarkably inhibited UACC-1598 cells invasion and migration. Further, RPL22L1 over-expression up-regulated the mesenchymal markers vimentin, fibronectin, and α-SMA, reduced expression of the epithelial markers E-cadherin, α-catenin, and β-catenin. RPL22L1 inhibition reduced expression of vimentin and N-cadherin. These results suggest that RPL22L1 induces epithelial-to-mesenchymal transition (EMT). Our data showed that the DMs amplified gene RPL22L1 is critical in maintaining the aggressive phenotype of OC and in triggering cell metastasis by inducing EMT. It could be employed as a novel prognostic marker and/or effective therapeutic target for OC.

We identified the neurons comprising the Drosophila mushroom body (MB), an associative center in invertebrate brains, and provide a comprehensive map describing their potential connections. Each of the 21 MB output neuron (MBON) types elaborates segregated dendritic arbors along the parallel axons of ∼2000 Kenyon cells, forming 15 compartments that collectively tile the MB lobes. MBON axons project to five discrete neuropils outside of the MB and three MBON types form a feedforward network in the lobes. Each of the 20 dopaminergic neuron (DAN) types projects axons to one, or at most two, of the MBON compartments. Convergence of DAN axons on compartmentalized Kenyon cell–MBON synapses creates a highly ordered unit that can support learning to impose valence on sensory representations. The elucidation of the complement of neurons of the MB provides a comprehensive anatomical substrate from which one can infer a functional logic of associative olfactory learning and memory.

So far, it has been suggested that phosphoenolpyruvate carboxylases (PEPCs) and PEPC kinases (PPCKs) fulfill several important non-photosynthetic functions. However, the biological functions of soybean PPCKs, especially in alkali stress response, are not yet well known. In previous studies, we constructed a Glycine soja transcriptional profile, and identified three PPCK genes (GsPPCK1, GsPPCK2 and GsPPCK3) as potential alkali stress responsive genes. In this study, we confirmed the induced expression of GsPPCK3 under alkali stress and investigated its tissue expression specificity by using quantitative real-time PCR analysis. Then we ectopically expressed GsPPCK3 in Medicago sativa and found that GsPPCK3 overexpression improved plant alkali tolerance, as evidenced by lower levels of relative ion leakage and MDA content and higher levels of chlorophyll content and root activity. In this respect, we further co-transformed the GsPPCK3 and SCMRP genes into alfalfa, and demonstrated the increased alkali tolerance of GsPPCK3-SCMRP transgenic lines. Further investigation revealed that GsPPCK3-SCMRP co-overexpression promoted the PEPC activity, net photosynthetic rate and citric acid content of transgenic alfalfa under alkali stress. Moreover, we also observed the up-regulated expression of PEPC, CS (citrate synthase), H(+)-ATPase and NADP-ME genes in GsPPCK3-SCMRP transgenic alfalfa under alkali stress. As expected, we demonstrated that GsPPCK3-SCMRP transgenic lines displayed higher methionine content than wild type alfalfa. Taken together, results presented in this study supported the positive role of GsPPCK3 in plant response to alkali stress, and provided an effective way to simultaneously improve plant alkaline tolerance and methionine content, at least in legume crops.

The microRNA319 (miR319) family is conserved among diverse plant species. In rice (Oryza sativa L.), the miR319 gene family is comprised of two members, Osa-miR319a and Osa-miR319b. We found that overexpressing Osa-miR319b in rice resulted in wider leaf blades and delayed development. Here, we focused on the biological function and potential molecular mechanism of the Osa-miR319b gene in response to cold stress in rice. The expression of Osa-miR319b was down-regulated by cold stress, and the overexpression of Osa-miR319b led to an enhanced tolerance to cold stress, as evidenced by higher survival rates and proline content. Also, the expression of a handful of cold stress responsive genes, such as DREB1A/B/C, DREB2A, TPP1/2, was increased in Osa-miR319b transgenic lines. Furthermore, we demonstrated the nuclear localization of the transcription factors, OsPCF6 and OsTCP21, which may be Osa-miR319b-targeted genes. We also showed that OsPCF6 and OsTCP21 expression was largely induced by cold stress, and the degree of induction was obviously repressed in plants overexpressing Osa-miR319b. As expected, the down-regulation of OsPCF6 and OsTCP21 resulted in enhanced tolerance to cold stress, partially by modifying active oxygen scavenging. Taken together, our findings suggest that Osa-miR319b plays an important role in plant response to cold stress, maybe by targeting OsPCF6 and OsTCP21.