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Financial management and decision-making of universities play an essential role in their development. Predicting fund revenue and expenditure of universities can provide a necessary basis for funds risk prevention. For the lack of solid data reference for financial management and funds risk prevention in colleges and universities, this paper presents a prediction model of University fund revenue and expenditure based on fuzzy time series with a periodic factor. Combined with the fuzzy time series, this prediction method introduces the periodic factor of university funds. The periodic factor is used to adjust the proportion of the predicted value of the fuzzy time series and the periodic observation value. A fund revenue prediction model and a fund expenditure prediction model are constructed, and an experiment is carried out with the actual financial data of a university in China. The experimental result shows the effectiveness of the proposed model, which can provide solid references for financial management and funds risk prevention in universities.

Based on 2010-2019 Chinese logistics listed companies as research samples, the paper used the binary Logit model measuring degree of financing constraints. The Kernel density function and Markov chain model are used to forecast China listed companies financing logistics dynamic constraints and business performance growth. Furthermore the stock of knowledge was chosen as a threshold variable to explore the impact of financing constraints on corporate performance growth of listed logistics enterprises. We find that the degree of financing constraints of logistics enterprises in our country has not been significantly eased. Corporate performance has not changed significantly and there are no obvious spatial gap and polarization with the passage of time. The impact of financing constraints on the corporate performance growth of logistics enterprises in China has a double threshold effect of knowledge stock, and has an inhibitory effect that first increases and then decreases. This is because in the short term, the investment of knowledge stock by enterprises can crowd out more corporate liquidity, and in the long run, it is related to the conversion rate of the knowledge stock itself. Because of the uneven regional distribution of resources and differences in the degree of economic development, there is a growing disincentive effect in central China as the stock of knowledge accumulates.

In the global trade landscape, ports are not only critical nodes for the transportation of goods but also increasingly recognized as key factors driving sustainable development through their green competitiveness. This paper takes a green competitiveness perspective to delve into the interactive relationship between port development and the hinterland economy, aiming to provide a theoretical foundation and policy recommendations for the green development of ports. An evaluation index system for green competitiveness of ports was constructed, and a combination of the Slacks-Based Measure (SBM) and the Entropy Weighted-Technique for Order Preference by Similarity to Ideal Solution (EW-TOPSIS) method was employed to quantitatively measure and assess the 25 major coastal ports and their hinterland economic systems in China. The study reveals that the overall green competitiveness of these major coastal ports is on the rise, yet notable disparities exist among individual ports. Regionally, the green competitiveness of the Yangtze River Delta port group stands out, while that of the Bohai Rim, southeastern, Pearl River Delta, and southwestern coastal port groups is relatively low. Empirical analysis conducted in this paper demonstrates the positive impact of port green competitiveness on the hinterland economic system, particularly its significant role in enhancing the total and quality aspects of the hinterland economy. Furthermore, it was found that the green competitiveness of ports exerts a more pronounced promotional effect on the hinterland economies of the Yangtze River Delta and Pearl River Delta port groups compared to that on the Bohai Rim, southeastern, and southwestern coastal port groups. The results of this paper also hold important guiding value for optimizing the allocation of port resources, promoting port technological innovation, and improving port environmental management, contributing to the harmonious coexistence and long-term development of ports and their hinterlands. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairment (CI) is common among patients with chronic kidney disease (CKD), and is associated with a poor prognosis. We assessed the prevalence and associated factors of CI in patients with CKD. Methods: A systematic review and meta-analysis were conducted by searching PubMed, Embase, and the Web of Science through December 1, 2023. Random effects models were performed with subgroup analyses to further explore the heterogeneity. Results: 50 studies involving 25,289 CKD patients were included. The overall prevalence of CI was 40% (95% confidence interval 33–46). The pooled prevalence of CI was relatively higher in CKD patients from Africa (58%), Asia (44%) and America (37%). Attention and executive dysfunction appeared to be the most common manifestations. The prevalence of CI was higher among patients with hemodialysis (53%) and peritoneal dialysis (39%) than those without dialysis (32%) and post-kidney transplanted (26%). In addition, advanced age, the presence of diabetes and hypertension might increase the risk of CI in CKD patients. Conclusions: People with CKD have a high prevalence of CI, especially in patients with hemodialysis. An early and comprehensive screening for CI in CKD patients is needed to improve clinical outcomes. Trial registration: Registration number: PROSPERO (CRD42023412864) [ABSTRACT FROM AUTHOR]

The biochemistry of mussel adhesion has inspired the design of surface primers, adhesives, coatings and gels for technological applications. These mussel-inspired systems often focus on incorporating the amino acid 3,4-dihydroxyphenyl-L-alanine (Dopa) or a catecholic analog into a polymer. Unfortunately, effective use of Dopa is compromised by its susceptibility to auto-oxidation at neutral pH. Oxidation can lead to loss of adhesive function and undesired covalent cross-linking. Mussel foot protein 5 (Mfp-5), which contains ∼ 30 mole % Dopa, is a superb adhesive under reducing conditions but becomes nonadhesive after pH-induced oxidation. Here we report that the bidentate complexation of borate by Dopa to form a catecholato-boronate can be exploited to retard oxidation. Although exposure of Mfp-5 to neutral pH typically oxidizes Dopa, resulting in a>95% decrease in adhesion, inclusion of borate retards oxidation at the same pH. Remarkably, this Dopa-boronate complex dissociates upon contact with mica to allow for a reversible Dopa-mediated adhesion. The borate protection strategy allows for Dopa redox stability and maintained adhesive function in an otherwise oxidizing environment.

Vitamin E is essential for human health and plays positive roles in anti-oxidation. Previously, we detected large variation in vitamin E content among 161 oil palm accessions. In this study, twenty oil palm accessions with distinct variation in vitamin E contents (171.30 to 1 258.50 ppm) were selected for genetic variation analysis and developing functional markers associated with vitamin E contents. Thirty-seven homologous genes in oil palm belonging to vitamin E biosynthesis pathway were identified via BLASTP analysis, the lengths of which ranged from 426 to 25 717 bp (average 7 089 bp). Multiplex PCR sequencing for the 37 genes found 1 703 SNPs and 85 indels among the 20 oil palm accessions, with 226 SNPs locating in the coding regions. Clustering analysis for these polymorphic loci showed that the 20 oil palm accessions could be divided into five groups. Among these groups, group I included eight oil palm accessions whose vitamin E content (mean value: 893.50 ppm) was far higher than other groups (mean value 256.29 to 532.94 ppm). Correlation analysis between the markers and vitamin E traits showed that 134 SNP and 7 indel markers were significantly (p < 0.05) related with total vitamin E content. Among these functional markers, the indel EgTMT-1-24 was highly correlated with variation in vitamin E content, especially tocotrienol content. Our study identified a number of candidate function associated markers and provided clues for further research into molecular breeding for high vitamin E content oil palm.

BackgroundMany reviews and meta-analyses had been conducted to investigate risk factors for sleep disorders in the general population. However, no similar research has been performed in the military population though insomnia and sleep-disordered breathing are quite prevalent in that population.ObjectivesTo investigate risk factors for insomnia and sleep-disordered breathing in military personnel.MethodsA systematic literature search was performed from inception to March 2021 and 6496 records were produced. Two authors independently screened records for eligibility. Results were presented as odds ratios, and a random-effect model was used to pool results. Data analysis was performed respectively according to military personnel type (i.e., veteran, active-duty personnel). Risk factors were sorted into three categories: sociodemographic, army-specific, and comorbidity. This meta-analysis was registered in PROSPERO before data analysis (registration No: CRD42020221696).ResultsTwenty-seven articles were finally included in the quantitative analysis. For sleep-disordered breathing in active-duty personnel, four sociodemographic (i.e., overweight/obesity, higher body mass index, male gender, >35 years old) and one comorbidity (i.e., depression) risk factors were identified. For insomnia in active-duty personnel, four sociodemographic (i.e., aging, alcohol dependence, white race, and female gender), two army-specific (i.e., deployment experience, combat experience), and four comorbidity (i.e., depression, post-traumatic stress disorder, traumatic brain injury, and anxiety) risk factors were identified. For insomnia in veterans, one army-specific (i.e., combat experience) and one comorbidity (i.e., post-traumatic stress disorder) risk factor was identified.ConclusionsSeveral risk factors were identified for insomnia and sleep-disordered breathing in the current meta-analysis. Risk factors for veterans and active-duty personnel were partially different. Research on sleep breathing disorders remains limited, and more convincing evidence would be obtained with more relevant studies in the future.

BackgroundUnderstanding risk factors for short- and long-term COVID-19 outcomes have implications for current guidelines and practice. We study whether early identified risk factors for COVID-19 persist one year later and through varying disease progression trajectories.MethodsThis was a retrospective study of 6,731 COVID-19 patients presenting to Michigan Medicine between March 10, 2020 and March 10, 2021. We describe disease progression trajectories from diagnosis to potential hospital admission, discharge, readmission, or death. Outcomes pertained to all patients: rate of medical encounters, hospitalization-free survival, and overall survival, and hospitalized patients: discharge versus in-hospital death and readmission. Risk factors included patient age, sex, race, body mass index, and 29 comorbidity conditions.ResultsYounger, non-Black patients utilized healthcare resources at higher rates, while older, male, and Black patients had higher rates of hospitalization and mortality. Diabetes with complications, coagulopathy, fluid and electrolyte disorders, and blood loss anemia were risk factors for these outcomes. Diabetes with complications, coagulopathy, fluid and electrolyte disorders, and blood loss were associated with lower discharge and higher inpatient mortality rates.ConclusionsThis study found differences in healthcare utilization and adverse COVID-19 outcomes, as well as differing risk factors for short- and long-term outcomes throughout disease progression. These findings may inform providers in emergency departments or critical care settings of treatment priorities, empower healthcare stakeholders with effective disease management strategies, and aid health policy makers in optimizing allocations of medical resources.

Land prices are the key problem of urban land management, with prices of residential land being the most sensitive and the strongest social reflection among the different land types. Exploring spatial and temporal variation of residential land prices and the effect of land market factors on residential land prices can help the government formulate targeted regulations and policies. This study analyzes the spatial and temporal evolution of residential land prices and the factors influencing the land market in the Beijing-Tianjin-Hebei region based on land transaction data from 2014-2017 using exploratory spatial data analysis (ESDA) and a geographically weighted regression (GWR) model. The results show the following: ① Residential land prices in Beijing and Tianjin are significantly higher than those in other regions, while Zhangjiakou, Chengde, and western mountainous areas have the lowest residential land prices. Over time, a development trend of residential land price polycentricity gradually emerged, and the locational correlation has gradually increased. ② Under the influence of the land finance model of local governments in China, three factors, namely, the land stock utilization rate, revenue from residential land transfers, and the growth of residential land transaction areas, have significantly contributed to the increase in residential land prices. ③ Under the land market supply and demand mechanism and government management, four indicators, namely, the land supply rate, the per capita residential land supply area, the degree of marketization of the residential land supply, and the frequency of residential land transactions, have suppressed the rise in residential land prices. ④ The overall effect of land market factors on residential land prices in the central and northern regions of Beijing, Tianjin and Hebei is stronger than that in the southern regions, which may be related to the more active land market and stricter macromanagement policies in Beijing, Tianjin and surrounding areas.

The spatial diffusion of epidemic disease follows distance decay law in geography and social physics, but the mathematical models of distance decay depend on concrete spatio-temporal conditions. This paper is devoted to modeling spatial diffusion patterns of COVID-19 stemming from Wuhan city to Hubei province, China. The modeling approach is to integrate analytical method and experimental method. The local gravity model is derived from allometric scaling and global gravity model, and then the parameters of the local gravity model are estimated by observational data and least squares calculation. The main results are as below. The local gravity model based on power law decay can effectively describe the diffusion patterns and process of COVID-19 in Hubei Province, and the goodness of fit of the gravity model based on negative exponential decay to the observational data is not satisfactory. Further, the goodness of fit of the model to data entirely became better and better over time, the size elasticity coefficient increases first and then decreases, and the distance attenuation exponent decreases first and then increases. Moreover, the significance of spatial autoregressive coefficient in the model is low, and the confidence level is less than 80%. The conclusions can be reached as follows. (1) The spatial diffusion of COVID-19 of Hubei bears long range effect, and the size of a city and the distance of the city to Wuhan affect the total number of confirmed cases. (2) Wuhan direct transmission is the main process in the spatial diffusion of COVID-19 in Hubei at the early stage, and the horizontal transmission between regions is not significant. (3) The effect of spatial lockdown and isolation measures taken by Chinese government against the transmission of COVID-19 is obvious. This study suggests that the role of urban gravity (size and distance) should be taken into account to prevent and control epidemic disease.

Temporal variability of the neural signal has been demonstrated to be closely related to healthy brain function. Meanwhile, the evolving brain functions are supported by dynamic relationships among brain regions. We hypothesized that the spatial variability of brain signal might provide important information about brain function. Here we used the spatial sample entropy (SSE) to investigate the spatial variability of neuroimaging signal during a steady-state presented face detection task. Lower SSE was found during task state than during resting state, associating with more repetitive functional interactions between brain regions. The standard deviation (SD) of SSE during the task was negatively related to the SD of reaction time, suggesting that the spatial pattern of neural activity is reorganized according to particular cognitive function and supporting the previous theory that greater variability is associated with better task performance. These results were replicated with reordered data, implying the reliability of SSE in measuring the spatial organization of neural activity. Overall, the present study extends the research scope of brain signal variability from the temporal dimension to the spatial dimension, improving our understanding of the spatiotemporal characteristics of brain activities and the theory of brain signal variability.

MicroRNAs (miRNAs) play vital roles in various biological processes under multiple stress conditions by leading to mRNA cleavage or translational repression. However, the detailed roles of miRNAs in cold acclimation in fish are still unclear. In the present study, high-throughput sequencing was performed to identify miRNAs from 6 small RNA libraries from the zebrafish embryonic fibroblast ZF4 cells under control (28°C, 30 days) and cold-acclimation (18°C, 30 days) conditions. A total of 414 miRNAs, 349 known and 65 novel, were identified. Among those miRNAs, 24 (19 known and 5 novel) were up-regulated, and 23 (9 known and 14 novel) were down-regulated in cold acclimated cells. The Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analyses indicated that the target genes of known differentially expressed miRNAs (DE-miRNA) are involved in cold acclimation by regulation of phosphorylation, cell junction, intracellular signal transduction, ECM-receptor interaction and so on. Moreover, both miR-100-3p inhibitor and miR-16b mimics could protect ZF4 cells under cold stress, indicating the involvement of miRNA in cold acclimation. Further study showed that miR-100-3p and miR-16b could regulate inversely the expression of their target gene (atad5a, cyp2ae1, lamp1, rilp, atxn7, tnika, btbd9), and that overexpression of miR-100-3p disturbed the early embryonic development of zebrafish. In summary, the present data show that miRNAs are closely involved in cold acclimation in zebrafish ZF4 cells and provide information for further understanding of the roles of miRNAs in cold acclimation in fish.

This study examines the reliability and validity of the Characteristics of Resilience in Sports Teams Inventory (CREST) in Chinese team athletes. A sample of 659 athletes (male = 355, female = 304) aged from 16-34 (M = 20.08, SD = 2.98) participated in this study. The scale was translated into Chinese using forward and back translation procedures by two independent translators. Questionnaires were administered online. Data was analysed using SPSS 19.0 and Mplus 6.0. Results showed that the items were understood by Chinese team sport athletes. Exploratory factor analysis showed that the Chinese version of CREST had two sub-dimensions as it was in the original scale. Confirmatory factor analysis further demonstrated that the two-structure model was confirmed in the Chinese team sports context. The Cronbach's alpha values of the scale was 0.842, and the test-retest reliability coefficient of one-month interval was 0.836. It is concluded that the Chinese version of CREST can be used as a valid and reliable tool to assess team resilience in China and can be helpful and applicable in helping sports psychologists understand team resilience. Future studies should further examine the psychometric properties of the scale among world-class athletes and develop a team resilience measurement tool based on Chinese traditional culture.

Bloodstream infection (BSI) is the major cause of mortality in acute lymphocytic leukemia (ALL). Causative pathogens in BSI originate from the gut microbiota due to an increase in intestinal permeability, a process known as bacterial translocation (BT). The gut microbiota in physiological conditions is controlled by a large number of immune cells as part of the gut-associated lymphoid tissue (GALT).The aim of the current study was to investigate the mechanism of bacterial translocation in leukemia by identifying and characterizing alterations in the GALT in leukemic mouse model. Our studies revealed a severe impairment of the GALT characterized by a loss of lymphatic cells in ALL, which eventually led to BSI. We identified differentially expressed genes in the intraepithelium and the lamina propria, which may contribute to BT and to the impairment of lymphocyte migration.

Bloodstream infection (BSI) is a life-threatening condition characterized by the presence of pathogens in the blood. It is associated with increased morbidity and mortality, and has to be treated promptly as mortality increases with every hour of delayed treatment. Therefore, rapid and sensitive diagnosis of BSI is essential. The routine diagnostic method for BSI is blood culture, which can only detect culturable pathogens and takes several days to obtain results. The 16S rRNA gene is present in all bacteria and is commonly used as a target for universal bacterial detection in rapid molecular assays such as PCR. However, molecular detection of the 16S gene is hampered by the large amount of human DNA found in blood samples, making diagnostic results aspecific and less sensitive. We have optimized the selection of PCR primers targeting the 16S rRNA gene to avoid cross-reaction with human DNA background. The developed method increases specificity and sensitivity for pathogen diagnosis, and provides rapid and accurate pathogen detection for rare bacterial DNA in the presence of abundant host DNA.

Early ripening apples are usually used for fresh marketing because of short storage life, although they are with high acid and low sugar contents. Understanding the malate metabolism in fleshy fruit and underpinning process during ripening is crucial for particular crop improvement where acidity is a concern for direct consumption or further processing. In this research, a traditional Chinese apple cultivar 'Hongyu', which belongs to early ripening apple cultivar, were freshly harvested at commercial maturity stage (120 Days after full bloom) and used for different storage temperature (4°C, 20°C) and UV-C treatment (following storage at 20°C after treatment). Simple sugars (glucose, sucrose, and fructose) and organic acids (malic, and oxalic) were assessed after 14 d of storage. Compared to fruits stored at 20°C, the malate content in fruits stored at 4°C significantly higher, while it was decreased significantly in UV-C treated fruits stored at 20°C after 14 d of storage. The sugar content was almost similar throughout the UV-C-treated fruits and fruits stored at different temperature. The higher ratios of total sugars to total organic acids in UV-C treated fruits after 14 d suggest that UV-C treatment has the potential to improve the taste of early ripening apple cultivars. Considering the significant difference in malate the samples at 14 d of storage were subjected for RNA-seq analysis. Transcriptome analysis revealed that the phenomena underlying this change were governed by metabolism of malate by the regulation of NADP-malic enzyme (NADP-ME) and phosphoenolpyruvate carboxylase kinase (PEPCK) in apple during postharvest storage. This transcriptome profiling results have specified the transcript regulation of malate metabolism and lead to possible taste improvement without affecting the other fruit quality attributes.

The pygmy killer whale (Feresa attenuata) (PKW) is a tropical and subtropical marine mammal commonly found in the Atlantic, Indian and Pacific oceans. Since the PKWs live in offshore protected territories, they are rarely seen onshore. Hence, PKW are one of the most poorly understood oceanic species of odontocetes. The dermal tissue comes primarily from stranding events that occur along the coast of the Shantou, Guangdong, China. The sampled tissues were immediately processed and attached on collagen-coated 6-well tissue culture plate. The complete medium (DMEM and Ham's F12, fetal bovine serum, antibiotic and essential amino acids) was added to the culture plates. The primary culture (PKW-LWH) cells were verified as fibroblast by vimentin and karyotype analyses, which revealed 42 autosomes and two sex chromosomes X and Y. Following transfection of PKW-LWH cells with a plasmid encoding, the SV40 large T-antigens and the transfected cells were isolated and expanded. Using RT-PCR, western blot, immunofluorescence analysis and SV40 large T-antigen stability was confirmed. The cell proliferation rate of the fibroblast cells, PKW-LWHT was faster than the primary cells PKW-LWH with the doubling time 68.9h and 14.4h, respectively. In this study, we established PKW dermal fibroblast cell line for the first time, providing a unique opportunity for in vitro studies on the effects of environmental pollutants and pathogens that could be determined in PKW and/or Cetaceans.

OBJECTIVE:Tetranychus cinnabarinus (Boisduval) is an agricultural mite pest threatens crops throughout the world, causing serious economic loses. Exploring the effects of acaricides on predatory mites is crucial for the combination of biological and chemical control of T. cinnabarinus. Neoseiulus californicus (McGregor) is one of the principal natural enemies of T. cinnabarinus, which can be applied in protected agriculture. In this study, the effects of sublethal concentrations of a new acaricide, SYP-9625 on two mite species, and the effects of the application concentration on predatory mite, N. californicus were assessed. The aim of the present study was to evaluate the effect of SYP-9625 on life parameters and predation capacity of N. californicus based on the concentration-response bioassay of T. cinnabarinus to explor the application of the new acaricide with natural enemy N. californicus. METHOD:All of the experiments were conducted under laboratory conditions [25 ± 1°C, 16: 8 h (L: D) and 75 ± 5% RH]. The sublethal concentrations LC10 (0.375μg/mL) and the LC30 (0.841μg/mL) against T. cinnabarinus and the application concentration (100μg/mL) against N. californicus were used to evaluate the effects of SYP-9625 on population parameters of N. californicus based on an age-stage, two-sex life table and its predation capacity by functional response. RESULT:cinnabarinus females treated with LC30 exhibited significantly reduced net reproductive rates (R0 = 11.02) in their offspring compared with females treated with LC10 (R0 = 14.96) and untreated females (R0 = 32.74). However, the intrinsic rate of increase (rm) and the finite rate of increase (λ) of N. californicus indicated that the application concentration of SYP-9625 had no significant negative effect on N. californicus eggs (rm = 0.277, λ = 1.319) compared to the control (rm = 0.292, λ = 1.338). Additionally, most population parameters of N. californicus showed a dose-dependent manner with the increase of the concentration of SYP-9625 against T. cinnabarinus. SYP-9625 also stimulated the control efficiency of N. californicus against immobile stages including eggs and larvae. CONCLUSION:This study demonstrated that sublethal concentrations of SYP-9625 can inhibit the population growth of T. cinnabarinus. In addition, the sublethal concentrations and the application concentration showed no effect on the population growth of N. californicus. These two advantages described above showed great commercial potential of this new acaricide based on population parameters of the two mite species and predation capacity of the predatory mite under laboratory conditions.

The present study was designed to evaluate the effects of Saccharomyces boulardii (Sb) and Bacillus subtilis B10 (Bs) on intestinal epithelial Toll like receptors (TLR), and Cytokine expression response to understand the intestinal epithelial innate immune mechanism in broilers. A total of 300 birds (Sanhuang broilers) were allotted into three groups (n = 100) and each divided into five replications (n = 20). Control group (Ctr) birds were fed basal diet, broilers in experimental groups received (1×108cfu/kg feed) Sb and Bs respectively in addition to basal diet for 72 days. The result showed significant increase in mRNA expression level of TLR2, TLR4 and TLR15. Down streaming MyD88, TRAF6, TAB2 and NF-κB mRNA level noted higher, in the jejunum and ileum as compared to control group. Meanwhile, IL-6, TNFα, IL-10, TGF-β expression levels showed high expression in the jejunum of Sb and Bs groups. IL-10 expression level increased in the ileum and IL-6, TNFα, IL-10 and TGF-β expression levels increased in the jejunum of Sb group. Levels of IL-1 β, IL-17, and IL-4, increased merely in Sb group. Ileal cytokines IL-1β, IL-17 and IL-4concentration were noted higher in Sb group, and IL-1β, and IL-4 levels were up-regulated in Bs group. The results indicated that the INF-γ and IL-8 level decreased in Sb and BS groups. Serum IgA and sIgA level increased in both treatment groups. Our findings illustrated that S. boulardii and B. subtilis B10 may have a role to induce mucosal immunity by activating the TLRs and cytokines expressions in broilers.

[This corrects the article DOI: 10.1371/journal.pone.0173917.].

Rectal enemas that contain prophylactic levels of anti-HIV microbicides such as tenofovir have emerged as a promising dosage form to prevent sexually transmitted HIV infections. The enema vehicle is promising due to its likely ability to deliver a large amount of drug along the length of the rectal canal. Computational models of microbicide drug delivery by enemas can help their design process by determining key factors governing drug transport and, more specifically, the time history and degree of protection. They can also inform interpretations of experimental pharmacokinetic measures such as drug concentrations in biopsies. The present work begins rectal microbicide PK modeling, for enema vehicles. Results here show that a paramount factor in drug transport is the time of enema retention; direct connectivity between enema fluid and the fluid within rectal crypts is also important. Computations of the percentage of stromal volume protected by a single enema dose indicate that even with only a minute of enema retention, protection of 100% can be achieved after around 14 minutes post dose. Concentrations in biopsies are dependent on biopsy thickness; and control and/or knowledge of thickness could improve accuracy and decrease variability in biopsy measurements. Results here provide evidence that enemas are a promising dosage form for rectal microbicide delivery, and offer insights into their rational design.

Respiratory syncytial virus (RSV) is a major respiratory pathogen of infants and young children. Multiple strains of both subgroup A and B viruses circulate during each seasonal epidemic. Genetic heterogeneity among RSV genomes, in large part due to the error prone RNA-dependent, RNA polymerase, could mediate variations in pathogenicity. We evaluated clinical strains of RSV for their ability to induce the innate immune response. Subgroup B viruses were used to infect human pulmonary epithelial cells (A549) and primary monocyte-derived human macrophages (MDM) from a variety of donors. Secretions of IL-6 and CCL5 (RANTES) from infected cells were measured following infection. Host and viral transcriptome expression were assessed using RNA-SEQ technology and the genomic sequences of several clinical isolates were determined. There were dramatic differences in the induction of IL-6 and CCL5 in both A549 cells and MDM infected with a variety of clinical isolates of RSV. Transcriptome analyses revealed that the pattern of innate immune activation in MDM was virus-specific and host-specific. Specifically, viruses that induced high levels of secreted IL-6 and CCL5 tended to induce cellular innate immune pathways whereas viruses that induced relatively low level of IL-6 or CCL5 did not induce or suppressed innate immune gene expression. Activation of the host innate immune response mapped to variations in the RSV G gene and the M2-1 gene. Viral transcriptome data indicated that there was a gradient of transcription across the RSV genome though in some strains, RSV G was the expressed in the highest amounts at late times post-infection. Clinical strains of RSV differ in cytokine/chemokine induction and in induction and suppression of host genes expression suggesting that these viruses may have inherent differences in virulence potential. Identification of the genetic elements responsible for these differences may lead to novel approaches to antiviral agents and vaccines.

African oil palm (Elaeis guineensis) is an important oil crop grown in tropical region and sensitive to low temperature along with high tolerance to salt and drought stresses. Since the WRKY transcription factor family plays central roles in the regulation of plant stress tolerance, 95 genes belonging to the WRKY family were identified and characterized in oil palm genome. Gene structure analysis showed that EgWRKY genes have considerable variation in intron number (0 to 12) and gene length (477bp to 89,167 bp). Duplicated genes identification indicated 32 EgWRKY genes originated from segmental duplication and two from tandem duplication. Based on transcriptome data, most EgWRKY genes showed tissue-specific expression patterns and their expression could be induced under cold stress. Furthermore, six EgWRKY genes with more than two-folded increased expression level under cold stress were validated by RT-qPCR, which has higher expression level in cold, drought and high salinity treatment. The identification and characterization of WRKY gene family showed that EgWRKY were associated with a wide range of abiotic stress responses in Elaeis guineensis and some EgWRKY members with high expression levels could be selected for further research in analyzing their functions in the stress response in African oil palm.

The Enterovirus genus of the family of Picornaviridae consists of 9 species of Enteroviruses and 3 species of Rhinoviruses based on the latest virus taxonomy. Those viruses contribute significantly to respiratory and digestive disorders in human and animals. Out of 9 Enterovirus species, Enterovirus E-G are closely related to diseases affecting on livestock industry. While enterovirus infection has been increasingly reported in cattle and swine, the enterovirus infections in small ruminants remain largely unknown.Virology, molecular and bioinformatics methods were employed to characterize a novel enterovirus CEV-JL14 from goats manifesting severe diarrhea with morbidity and mortality respectively up to 84% and 54% in China.CEV-JL14 was defined and proposed as a new Enterovirus species L within the genus of Enterovirus of the family Picornaviridae. CEV-JL14 had a complete genome sequence of 7461 nucleotides with an ORF encoding 2172 amino acids, and shared 77.1% of genomic sequence identity with TB4-OEV, an ovine enterovirus. Comparison of 5'-UTR and structural genes of CEV-JL14 with known Enterovirus species revealed highly genetic variations among CEV-JL14 with known Enterovirus species. VP1 nucleotide sequence identities of CEV-14 were 51.8%-53.5% with those of Enterovirus E and F, 30.9%-65.3% with Enterovirus G, and 43.8-51. 5% with Enterovirus A-D, respectively. CEV-JL14 was proposed as a novel species within the genus of Enterovirus according to the current ICTV demarcation criteria of enteroviruses.CEV-JL14 clustered phylogenetically to neither Enterovirus E and F, nor to Enterovirus G. It was defined and proposed as novel species L within the genus of Enterovirus. This is the first report of caprine enterovirus in China, the first complete genomic sequence of a caprine enterovirus revealed, and the unveiling of significant genetic variations between ovine enterovirus and caprine enterovirus, thus broadening the current understanding of enteroviruses.

To investigate the relationship between preoperative expectations and actual postoperative outcomes of visual function (VF) among patients undergoing first eye cataract surgery.A longitudinal study of 182 patients from hospitals in urban Southern China were surveyed prior to surgery and 3 month after cataract surgery regarding their preoperative, expected postoperative and actual postoperative VF for each of the items on the Catquest-9SF and their satisfaction with cataract surgery. In addition, detailed clinical data were collected preoperatively and postoperatively.The majority of cataract patients in urban Southern China had high expectations for VF outcomes after cataract surgery and in most cases postoperative outcomes achieved the expected level of improvement. The mean (standard deviation, SD) preoperative Catquest-9SF score was 15.7 (5.86) and the mean (SD) expected postoperative score was 26.3 (2.93). The discrepancy between actual and expected improvement was significantly correlated with patients' health literacy, presence of systemic and ocular comorbidity, preoperative visual acuity of the surgery eye, LOCS III nuclear opalescence and cortical cataract grading.Cataract patients in urban Southern China had high expectations for surgery outcomes. Patients with low level of health literacy and the presence of systemic and ocular comorbidity may need a comprehensive counseling to decrease the discrepancy regarding expected and actual outcomes.

Diabetic retinopathy (DR) is a severe complication of chronic diabetes. The C1q/TNF-related protein family (CTRPs) has been demonstrated to exert protective effects against obesity and atherosclerosis in animal studies. Heretofore, the association between circulating CTRPs and DR patients has been unexplored. In the current study, we attempt to define this association, as well as the effect of CTRPs upon DR pathophysiology.The present investigation is a case control study that enrolled control subjects and type 2 diabetes mellitus (T2DM) patients diagnosed with DR. Serum CTRPs and sVACM-1 were determined by ELISA.Serum CTRP3 and CTRP5 levels were markedly decreased in patients with T2DM compared to controls (p

To analyze the validity of the Hospital Anxiety and Depression Scale (HADS) among Chinese cataract population.A total of 275 participants with unilateral or bilateral cataract were recruited to complete the Chinese version of HADS. The patients' demographic and ophthalmic characteristics were documented. Rasch analysis was conducted to examine the model fit statistics, the thresholds ordering of the polytomous items, targeting, person separation index and reliability, local dependency, unidimentionality, differential item functioning (DIF) and construct validity of the HADS individual and summary measures.Rasch analysis was performed on anxiety and depression subscales as well as HADS-Total score respectively. The items of original HADS-Anxiety, HADS-Depression and HADS-Total demonstrated evidence of misfit of the Rasch model. Removing items A7 for anxiety subscale and rescoring items D14 for depression subscale significantly improved Rasch model fit. A 12-item higher order total scale with further removal of D12 was found to fit the Rasch model. The modified items had ordered response thresholds. No uniform DIF was detected, whereas notable non-uniform DIF in high-ability group was found. The revised cut-off points were given for the modified anxiety and depression subscales.The modified version of HADS with HADS-A and HADS-D as subscale and HADS-T as a higher-order measure is a reliable and valid instrument that may be useful for assessing anxiety and depression states in Chinese cataract population.

Isoflavonoids are secondary metabolites that play a variety of roles in plant-microbe interactions and plant defenses against abiotic stresses. Here we report a new MYB transcription factor (TF) gene, GmMYBJ3, that is involved in the isoflavonoids biosynthesis. The GmMYBJ3 gene is 1,002 bp long and encodes a protein of 333 amino acids. Amino acid sequence analysis showed that GmMYBJ3 is a typical R2R3 MYB TF. Yeast expression experiment demonstrated that GmMYBJ3 has its transcription activity in the nucleus and is transiently expressed in onion epidermal cells. The GmMYBJ3 gene was transformed into soybean and the expression activity of the GmMYBJ3 gene was significantly positively correlated with total isoflavonoid accumulation in soybean. Transient expression assays indicated that GmMYBJ3 can activate CHS8 expression. Furthermore, we analyzed the expressions of several genes known involved in the isoflavonoid biosynthesis, including CHS8, CHI1A, PAL1, IFS2 and F3H, in the GmMYBJ3 transgenic plants. The results showed that the expression levels of CHS8 and CHI1A were significantly increased in the transgenic plants compared to wild-type plants, but those of PAL1, IFS2 and F3H remained similar between the transgenic and wild-type plants. These results suggest that GmMYBJ3 participates in the isoflavonoid biosynthesis through regulation of CHS8 and CHI1A in soybean.

Recently, targeting cancer stem cells (CSCs) metabolism is becoming a promising therapeutic approach to improve cancer treatment outcomes. However, knowledge of the metabolic state of CSCs in small cell lung cancer is still lacking. In this study, we found that CSCs had significantly lower oxygen consumption rate and extracellular acidification rate than non-stem cancer cells. Meanwhile, this subpopulation of cells consumed less glucose, produced less lactate and maintained lower ATP levels. We also revealed that CSCs could produce more ATP through mitochondrial substrate-level phosphorylation during respiratory inhibition compared with non-stem cancer cells. Furthermore, they were more sensitive to suppression of oxidative phosphorylation. Therefore, oligomycin (inhibitor of oxidative phosphorylation) could severely impair sphere-forming and tumor-initiating abilities of CSCs. Our work suggests that CSCs represent metabolically inactive tumor subpopulations which sustain in a state showing low metabolic activity. However, mitochondrial substrate-level phosphorylation of CSCs may be more active than that of non-stem cancer cells. Moreover, CSCs showed preferential use of oxidative phosphorylation over glycolysis to meet their energy demand. These results extend our understanding of CSCs metabolism, potentially providing novel treatment strategies targeting metabolic pathways in small cell lung cancer.

Clinical studies have identified hypoadiponectinemia as an independent hypertension risk factor. It is known that adiponectin (APN) can directly cause vasodilation, but the doses required exceed physiologic levels several fold. In the current study, we determine the effect of physiologically relevant APN concentrations upon vascular tone, and investigate the mechanism(s) responsible. Physiologic APN concentrations alone induced no significant vasorelaxation. Interestingly, pretreatment of wild type mouse aortae with physiologic APN levels significantly enhanced acetylcholine (ACh)-induced vasorelaxation (P

Non-syndromic tooth agenesis (or non-syndromic congenitally missing tooth) is one of the most common congenital defects in humans affecting the craniofacial function and appearance. Single nucleotide polymorphisms (SNPs) have been associated with an individual's susceptibility to these anomalies. The aim of the present study was therefore to investigate the roles of the potentially functional SNPs of BMP2 in the occurrence of tooth agenesis. Overall, four potentially functional SNPs of BMP2 (rs15705, rs235768, rs235769 and rs3178250) were selected, and their associations with the susceptibility of tooth agenesis were evaluated in a case-control study of 335 non-syndromic tooth agenesis cases and 444 healthy controls. The SNPs rs15705 and rs3178250 were found to be associated with an individual's risk of tooth agenesis (P = 0.046 and P = 0.039, respectively). Both SNPs showed an increased risk of mandibular incisor agenesis (rs15705, AA/AC vs. CC = 1.58, 95% CI = [1.06-2.34], P = 0.024; rs3178250, TT/TC vs. CC = 1.60, 95% CI = [1.08-2.37], P = 0.020). Bioinformatics analysis indicated that these two SNPs located at the 3'-untranslated region (3'-UTR) of BMP2 might alter the binding ability of miR-1273d and miR-4639-5p, respectively, which was confirmed by luciferase activity assays in the 293A and COS7 cell lines (P < 0.001 in 293A and P < 0.01 in COS7 for miR-1273d; and P < 0.001 in both cells for miR-4639-5p). Furthermore, BMP2 mRNA expression decreased after transfecting either miR-1273d or miR-4639-5p into these two cell lines (P < 0.01 in 293A and P < 0.001 in COS7 for miR-1273d, and P < 0.01 in both cell lines for miR-4639-5p). Taken together, our findings indicate that rs15705 and rs317250 are associated with the susceptibility of non-syndromic tooth agenesis by possibly affecting miRNAs and mRNA interaction.

As one of the major pathogens, bovine viral diarrhea virus caused a significant economic loss to the livestock industry worldwide. Although BVDV infections have increasingly been reported in China in recent years, the molecular aspects of those BVDV strains were barely characterized. In this study, we reported the identification and characterization of a novel BVDV isolate designated as SD-15 from cattle, which is associated with an outbreak characterized by severe hemorrhagic and mucous diarrhea with high morbidity and mortality in Shandong, China. SD-15 was revealed to be a noncytopathic BVDV, and has a complete genomic sequence of 12,285 nucleotides that contains a large open reading frame encoding 3900 amino acids. Alignment analysis showed that SD-15 has 93.8% nucleotide sequence identity with BVDV ZM-95 isolate, a previous BVDV strain isolated from pigs manifesting clinical signs and lesions resembling to classical swine fever. Phylogenetic analysis clustered SD-15 to a BVDV-1m subgenotype. Analysis of the deduced amino acid sequence of glycoproteins revealed that E2 has several highly conserved and variable regions within BVDV-1 genotypes. An additional N-glycosylation site (240NTT) was revealed exclusively in SD-15-encoded E2 in addition to four potential glycosylation sites (Asn-X-Ser/Thr) shared by all BVDV-1 genotypes. Furthermore, unique amino acid and linear epitope mutations were revealed in SD-15-encoded Erns glycoprotein compared with known BVDV-1 genotype. In conclusion, we have isolated a noncytopathic BVDV-1m strain that is associated with a disease characterized by high morbidity and mortality, revealed the complete genome sequence of the first BVDV-1m virus originated from cattle, and found a unique glycosylation site in E2 and a linear epitope mutation in Erns encoded by SD-15 strain. Those results will broaden the current understanding of BVDV infection and lay a basis for future investigation on SD-15-related pathogenesis.

Limited availability of the n-3 fatty acids EPA and DHA have led to an interest in better understanding of the n-3 biosynthetic pathway and its regulation. The biosynthesis of alpha-linolenic acid to EPA and DHA involves several complex reaction steps including desaturation-, elongation- and peroxisomal beta-oxidation enzymes. The aims of the present experiments were to gain more knowledge on how this biosynthesis is regulated over time by different doses and fatty acid combinations. Hepatocytes isolated from salmon were incubated with various levels and combinations of oleic acid, EPA and DHA. Oleic acid led to a higher expression of the Δ6 fatty acid desaturase (fad) genes Δ6fad_a, Δ6fad_b, Δ6fad_c and the elongase genes elovl2 compared with cells cultured in medium enriched with DHA. Further, the study showed rhythmic variations in expression over time. Levels were reached where a further increase in specific fatty acids given to the cells not stimulated the conversion further. The gene expression of Δ6fad_a_and Δ6fad_b responded similar to fatty acid treatment, suggesting a co-regulation of these genes, whereas Δ5fad and Δ6fad_c showed a different regulation pattern. EPA and DHA induced different gene expression patterns, especially of Δ6fad_a. Addition of radiolabelled alpha-linolenic acid to the hepatocytes confirmed a higher degree of elongation and desaturation in cells treated with oleic acid compared to cells treated with DHA. This study suggests a complex regulation of the conversion process of n-3 fatty acids. Several factors, such as that the various gene copies are differently regulated, the gene expression show rhythmic variations and gene expression only affected to a certain level, determines when you get the maximum conversion of the beneficial n-3 fatty acids.

The hippocampal CA1 region is sensitive to hypoxic and ischemic injury but can be protected by ischemic preconditioning (IPC). However, the mechanism through which IPC protects hippocampal CA1 neurons is still under investigation. Additionally, the role of autophagy in determining the fate of hippocampal neurons is unclear. Here, we examined whether IPC induced autophagy to alleviate hippocampal CA1 neuronal death in vitro and in vivo with oxygen glucose deprivation (OGD) and bilateral carotid artery occlusion (BCCAO) models. Survival of hippocampal neurons increased from 51.5% ± 6.3% in the non-IPC group (55 min of OGD) to 77.3% ± 7.9% in the IPC group (15 min of OGD, followed by 55 min of OGD 24 h later). The number of hippocampal CA1 layer neurons increased from 182 ± 26 cells/mm2 in the non-IPC group (20 min of BCCAO) to 278 ± 55 cells/mm2 in the IPC group (1 min × 3 BCCAO, followed by 20 min of BCCAO 24 h later). Akt phosphorylation and microtubule-associated protein light chain 3 (LC3)-II/LC3-I expression were increased in the preconditioning group. Moreover, the protective effects of IPC were abolished only by inhibiting the activity of autophagy, but not by blocking the activation of Akt in vitro. Using in vivo experiments, we found that LC3 expression was upregulated, accompanied by an increase in neuronal survival in hippocampal CA1 neurons in the preconditioning group. The neuroprotective effects of IPC on hippocampal CA1 neurons were completely inhibited by treatment with 3-MA. In contrast, hippocampal CA3 neurons did not show changes in autophagic activity or beneficial effects of IPC. These data suggested that IPC may attenuate ischemic injury in hippocampal CA1 neurons through induction of Akt-independent autophagy.

We aimed to measure prevalence of sleep disturbance in patients with differentiated thyroid cancer (DTC) by calculating Pittsburgh Sleep Quality Index (PSQI), and compare these data with patients with benign thyroid nodules or normal participants.Three groups of patients participated in this cross-sectional study. In the first group, 162 patients with DTC received total thyroidectomy, and then 131I therapy. The second group consisted of 84 patients with benign thyroid nodules, who received partial thyroidectomy. The third group was 78 normal healthy control cases. PSQI was used to assess the sleep quality. Inter-group differences were analyzed by Kruskal-Wallis test or independent samples T test. χ2 test was also used to check prevalence differences of poor sleep quality among the groups. Differences of PSQI score and poor sleep quality prevalence before and after 131I therapy in the same group of DTC participants were analyzed by paired T test and Mcnemar's test.Higher PSQI score (7.59 ± 4.21) and higher rate of poor sleep quality (54.32%) were shown in DTC patients than in any other group. After 131I therapy, PSQI score and prevalence of poor sleep quality in DTC patients increased significantly to 8.78 ± 4.72 and 70.99%. Then DTC patients were divided into two subgroups based on their metastatic status. DTC patients with metastasis (87/162 cases, 53.70%) had significantly higher PSQI score (10.87 ± 5.18) and higher prevalence of poor sleep quality (79.31%).DTC patients suffer from sleep disturbance, 131I therapy and awareness of metastatic status could worsen sleep problem. Psychological fear of cancer, nuclear medicine therapy and metastasis could be one major underlying reason. Longitude and interventional studies are necessary for further investigations.

To study willingness to pay for cataract surgery and surgical service provided by a senior cataract surgeon in urban Southern China.This study was a cross-sectional willingness-to-pay (WTP) interview using bidding formats. Two-hundred eleven persons with presenting visual impairment in either eye due to cataract were enrolled at a tertiary eye hospital. Participants underwent a comprehensive eye examination and a WTP interview for both surgery and service provided by a senior surgeon. Demographic information, socioeconomic status and clinical data were recorded.Among 211 (98% response rate) persons completing the interview, 53.6% were women and 80.6% were retired. About 72.2% had a monthly income lower than 1000 renminbi (US $161). A total of 189 (89.6%) were willing to pay for cataract and the median amount of WTP was 6000 renminbi (US$968). And 102 (50.7%) were willing to pay additional fees for surgery performed by a senior surgeon, and the median amount of WTP was 500 renminbi (US$81). In regression models adjusting for age and gender, persons with preexisting eye diseases other than cataract, were more likely to pay for cataract surgery and service provided by a senior surgeon (P = 0.04 for both).In urban China, cataract patients, especially those with preexisting eye conditions, are willing to pay additional fees for a senior surgeon. Moving to a system where the price of cataract surgery is proportional to the consultant' skill and expertise is possible and may have a potential impact on waiting list and quality of eye care. Further studies are needed to examine the impact of such pricing system on attitudes and choices of cataract patients.

Chilling stress is an important constraint for maize seed establishment in the field. In this study, a type of "on-off" thermoresponsive coating agent containing poly (N-isopropylacrylamide-co-butylmethacrylate) (Abbr. P(NIPAm-co-BMA)) hydrogel was developed to improve the chilling tolerance of coated maize seed. The P(NIPAm-co-BMA) hydrogel was synthesized by free-radical polymerization of N-isopropylacrylamide (NIPAm) and butylmethacrylate (BMA). Salicylic acid (SA) was loaded in the hydrogel as the chilling resistance agent. SA-loaded P(NIPAm-co-BMA) was used for seed film-coating of two maize varieties, Huang C (HC, chilling-tolerant) and Mo17 (chilling-sensitive), to investigate the coated seed germination and seedling growth status under chilling stress. The results showed that the hydrogel obtained a phase transition temperature near 12°C with a NIPAM to MBA weight ratio of 1: 0.1988 (w/w). The temperature of 12°C was considered the "on-off" temperature for chilling-resistant agent release; the SA was released from the hydrogel more rapidly at external temperatures below 12°C than above 12°C. In addition, when seedlings of both maize varieties suffered a short chilling stress (5°C), higher concentrations of SA-loaded hydrogel resulted in increased germination energy, germination percentage, germination index, root length, shoot height, dry weight of roots and shoots and protective enzyme activities and a decreased malondialdehyde content in coated maize seeds compared to single SA treatments. The majority of these physiological and biochemical parameters achieved significant levels compared with the control. Therefore, SA-loaded P(NIPAm-co-BMA), a nontoxic thermoresponsive hydrogel, can be used as an effective material for chilling tolerance in film-coated maize seeds.