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Blockchain-based applications are becoming more and more widespread in business operations. In view of the shortcomings of existing enterprise blockchain evaluation methods, this paper proposes a multi-source heterogeneous blockchain data quality evaluation model for enterprise business activities, so as to achieve efficient evaluation of business activity information consistency, credibility and value. This paper proposes a multi-source heterogeneous blockchain data quality assessment method for enterprise business activities, aiming at the problems that most of the data in enterprise business activities come from different data sources, information representation is inconsistent, information ambiguity between the same block chain is serious, and it is difficult to evaluate the consistency, credibility and value of information. The method firstly proposes an entity information representation method based on the Representation learning for fusing entity category information (CEKGRL) model, which introduces the triad structure of related entities in blockchain, then associates them with enterprise business activity categories, and carries out similarity calculation through contextual information to achieve blockchain information consistency assessment. After that, a trustworthiness characterization method is proposed based on information sources, information comments, and information contents, to obtain the trustworthiness assessment of the business. Finally, based on the information trustworthiness characterization, a value assessment method is introduced to assess the total value of business activity information in the blockchain, and a blockchain quality assessment model is constructed. The experimental results show that the proposed model has great advantages over existing methods in assessing inter-block consistency, intra-block activity information trustworthiness and the value of blockchain.

BackgroundThe COVID-19 pandemic has significantly affected maternal care services especially for minoritized individuals, creating challenges for both service users (i.e., African American and Hispanic pregnant/postpartum women) and maternal care providers (MCPs). Guided by a socioecological framework, this study aims to investigate the experiences of African American and Hispanic pregnant and postpartum women, as well as MCPs, in accessing and providing maternal care services during the COVID-19 pandemic in the Deep South.MethodsWe conducted semi-structured interviews with 19 African American women, 20 Hispanic women, and 9 MCPs between January and August 2022. Participants were recruited from Obstetrics and Gynecology clinics, pediatric clinics, and community health organizations in South Carolina, and all births took place in 2021. Interview transcripts were analyzed thematically.ResultsMaternal care utilization and provision were influenced by various factors at different socioecological levels. At the intrapersonal level, women's personal beliefs, fears, concerns, and stress related to COVID-19 had negative impacts on their experiences. Some women resorted to substance use as a coping strategy or home remedy for pregnancy-induced symptoms. At the interpersonal level, family and social networks played a crucial role in accessing care, and the discontinuation of group-based prenatal care had negative consequences. Participants reported a desire for support groups to alleviate the pressures of pregnancy and provide a platform for shared experiences. Language barriers were identified as an obstacle for Hispanic participants. Community-level impacts, such as availability and access to doulas and community health workers, provided essential information and support, but limitations in accessing doula support and implicit bias were also identified. At the institutional level, mandatory pre-admission COVID-19 testing, visitation restrictions, and reduced patient-MCP interactions were women's common concerns. Short staffing and inadequate care due to the impact of COVID-19 on the health care workforce were reported, along with anxiety among MCPs about personal protective equipment availability. MCPs emphasized the quality of care was maintained, with changes primarily attributed to safety protocols rather than a decline in care quality.ConclusionThe pandemic has disrupted maternal care services. To overcome these issues, health facilities should integrate community resources, adopt telehealth, and develop culturally tailored education programs for pregnant and postpartum women. Supporting MCPs with resources will enhance the quality of care and address health disparities in African American and Hispanic women.

Understanding the evolution of rural landscapes in metropolises during rapid urbanization is crucial for formulating policies to protect the rural ecological environment. In this study, remote sensing and geographical information system data, as well as applied landscape index analysis, are used to examine the spatiotemporal evolution of rural landscape patterns in the Beijing-Tianjin region of China, which has experienced rapid urbanization. The relationships between land use/land cover changes and changes in rural landscape patterns are explored. The results revealed significant spatial differences in the rural landscapes in the Beijing-Tianjin region; farmland and forestland were the main types of landscapes, creating a "mountain-field-sea" natural landscape pattern. The conversion of rural landscapes in the Beijing-Tianjin region involved mainly the conversion of farmland to urban areas, with few exchanges between other landscape types. The urban areas in the Beijing-Tianjin region increased by 3% per decade; farmland decreased at the same rate. Additionally, the rural landscape patterns in the Beijing-Tianjin region were dominated by fragmentation, dispersion, and heterogeneity and moved from complex to regular. Water bodies displayed the most fragmented natural landscape; their number of patches increased by 36%, though their network characteristics were maintained. Forestland was the most concentrated natural landscape. In this study, theoretical support and a scientific reference for the optimization of rural landscape patterns and the improvement in rural living environments in rapidly urbanizing areas are provided.

As the number of transgenic livestock increases, reliable detection and molecular characterization of transgene integration sites and copy number are crucial not only for interpreting the relationship between the integration site and the specific phenotype but also for commercial and economic demands. However, the ability of conventional PCR techniques to detect incomplete and multiple integration events is limited, making it technically challenging to characterize transgenes. Next-generation sequencing has enabled cost-effective, routine and widespread high-throughput genomic analysis. Here, we demonstrate the use of next-generation sequencing to extensively characterize cattle harboring a 150-kb human lactoferrin transgene that was initially analyzed by chromosome walking without success. Using this approach, the sites upstream and downstream of the target gene integration site in the host genome were identified at the single nucleotide level. The sequencing result was verified by event-specific PCR for the integration sites and FISH for the chromosomal location. Sequencing depth analysis revealed that multiple copies of the incomplete target gene and the vector backbone were present in the host genome. Upon integration, complex recombination was also observed between the target gene and the vector backbone. These findings indicate that next-generation sequencing is a reliable and accurate approach for the molecular characterization of the transgene sequence, integration sites and copy number in transgenic species. [ABSTRACT FROM AUTHOR]

Amyloid precursor protein cleaving enzyme 1 (BACE1), an aspartyl protease, initiates processing of the amyloid precursor protein (APP) into β-amyloid (Aβ); the peptide likely contributes to development of Alzheimer's disease (AD). BACE1 is an attractive therapeutic target for AD treatment, but it exhibits other physiological activities and has many other substrates besides APP. Thus, inhibition of BACE1 function may cause adverse side effects. Here, we present a peptide, S1, isolated from a peptide library that selectively inhibits BACE1 hydrolytic activity by binding to the β-proteolytic site on APP and Aβ N-terminal. The S1 peptide significantly reduced Aβ levels in vitro and in vivo and inhibited Aβ cytotoxicity in SH-SY5Y cells. When applied to APPswe/PS1dE9 double transgenic mice by intracerebroventricular injection, S1 significantly improved the spatial memory as determined by the Morris Water Maze, and also attenuated their Aβ burden. These results indicate that the dual-functional peptide S1 may have therapeutic potential for AD by both reducing Aβ generation and inhibiting Aβ cytotoxicity. [ABSTRACT FROM AUTHOR]

Previous studies on the immunoglobulin (Ig) genes in avian species are limited (mainly to galliformes and anseriformes) but have revealed several interesting features, including the absence of the IgD and Igk encoding genes, inversion of the IgA encoding gene and the use of gene conversion as the primary mechanism to generate an antibody repertoire. To better understand the Ig genes and their evolutionary development in birds, we analyzed the Ig genes in the ostrich (Struthio camelus), which is one of the most primitive birds. Similar to the chicken and duck, the ostrich expressed only three IgH chain isotypes (IgM, IgA and IgY) and l light chains. The IgM and IgY constant domains are similar to their counterparts described in other vertebrates. Although conventional IgM, IgA and IgY cDNAs were identified in the ostrich, we also detected a transcript encoding a short membrane-bound form of IgA (lacking the last two CH exons) that was undetectable at the protein level. No IgD or k encoding genes were identified. The presence of a single leader peptide in the expressed heavy chain and light chain V regions indicates that gene conversion also plays a major role in the generation of antibody diversity in the ostrich. Because the ostrich is one of the most primitive living aves, this study suggests that the distinct features of the bird Ig genes appeared very early during the divergence of the avian species and are thus shared by most, if not all, avian species. [ABSTRACT FROM AUTHOR]

Background: The mammary gland is a conserved site of lipoprotein lipase expression across species and lipoprotein lipase attachment to the luminal surface of mammary gland vascular endothelial cells has been implicated in the direction of circulating triglycerides into milk synthesis during lactation. Principal Findings: Here we report generation of transgenic mice harboring a human lipoprotein lipase gene driven by a mammary gland-specific promoter. Lipoprotein lipase levels in transgenic milk was raised to 0.16 mg/ml, corresponding to an activity of 8772.95 mU/ml. High lipoprotein lipase activity led to a significant reduction of triglyceride concentration in milk, but other components were largely unchanged. Normal pups fed with transgenic milk showed inferior growth performances compared to those fed with normal milk. Conclusion: Our study suggests a possibility to reduce the triglyceride content of cow milk using transgenic technology. [ABSTRACT FROM AUTHOR]

Background: Genetic ancestry is known to impact outcomes of genotype-phenotype studies that are designed to identify risk for common diseases in human populations. Failure to control for population stratification due to genetic ancestry can significantly confound results of disease association studies. Moreover, ancestry is a critical factor in assessing lifetime risk of disease, and can play an important role in optimizing treatment. As modern medicine moves towards using personal genetic information for clinical applications, it is important to determine genetic ancestry in an accurate, cost-effective and efficient manner. Self-identified race is a common method used to track and control for population stratification; however, social constructs of race are not necessarily informative for genetic applications. The use of ancestry informative markers (AIMs) is a more accurate method for determining genetic ancestry for the purposes of population stratification. Methodology/Principal Findings: Here we introduce a novel panel of 36 microsatellite (MSAT) AIMs that determines continental admixture proportions. This panel, which we have named Continental Ancestry Informative Markers or CoAIMs, consists of MSAT AIMs that were chosen based upon their measure of genetic variance (Fst), allele frequencies and their suitability for efficient genotyping. Genotype analysis using CoAIMs along with a Bayesian clustering method (STRUCTURE) is able to discern continental origins including Europe/Middle East (Caucasians), East Asia, Africa, Native America, and Oceania. In addition to determining continental ancestry for individuals without significant admixture, we applied CoAIMs to ascertain admixture proportions of individuals of self declared race. Conclusion/Significance: CoAIMs can be used to efficiently and effectively determine continental admixture proportions in a sample set. The CoAIMs panel is a valuable resource for genetic researchers performing case-control genetic association studies, as it can control for the confounding effects of population stratification. The MSAT-based approach used here has potential for broad applicability as a cost effective tool toward determining admixture proportions. [ABSTRACT FROM AUTHOR]

Large-scale production of biopharmaceuticals by current bioreactor techniques is limited by low transgenic efficiency and low expression of foreign proteins. In general, a bacterial artificial chromosome (BAC) harboring most regulatory elements is capable of overcoming the limitations, but transferring BAC into donor cells is difficult. We describe here the use of cattle mammary bioreactor to produce functional recombinant human lactoferrin (rhLF) by a novel procedure of transgenic cloning, which employs microinjection to generate transgenic somatic cells as donor cells. Bovine fibroblast cells were co-microinjected for the first time with a 150-kb BAC carrying the human lactoferrin gene and a marker gene. The resulting transfection efficiency of up to 15.79±10-2 percent was notably higher than that of electroporation and lipofection. Following somatic cell nuclear transfer, we obtained two transgenic cows that secreted rhLF at high levels, 2.5 g/l and 3.4 g/l, respectively. The rhLF had a similar pattern of glycosylation and proteolytic susceptibility as the natural human counterpart. Biochemical analysis revealed that the iron-binding and releasing properties of rhLF were identical to that of native hLF. Importantly, an antibacterial experiment further demonstrated that rhLF was functional. Our results indicate that co-microinjection with a BAC and a marker gene into donor cells for somatic cell cloning indeed improves transgenic efficiency. Moreover, the cattle mammary bioreactors generated with this novel procedure produce functional rhLF on an industrial scale. [ABSTRACT FROM AUTHOR]

As a novel form of human machine interaction (HMI), hand gesture recognition (HGR) has garnered extensive attention and research. The majority of HGR studies are based on visual systems, inevitably encountering challenges such as depth and occlusion. On the contrary, data gloves can facilitate data collection with minimal interference in complex environments, thus becoming a research focus in fields such as medical simulation and virtual reality. To explore the application of data gloves in dynamic gesture recognition, this paper proposes a data glove-based dynamic gesture recognition model called the Attention-based CNN-BiLSTM Network (A-CBLN). In A-CBLN, the convolutional neural network (CNN) is employed to capture local features, while the bidirectional long short-term memory (BiLSTM) is used to extract contextual temporal features of gesture data. By utilizing attention mechanisms to allocate weights to gesture features, the model enhances its understanding of different gesture meanings, thereby improving recognition accuracy. We selected seven dynamic gestures as research targets and recruited 32 subjects for participation. Experimental results demonstrate that A-CBLN effectively addresses the challenge of dynamic gesture recognition, outperforming existing models and achieving optimal gesture recognition performance, with the accuracy of 95.05% and precision of 95.43% on the test dataset.

BackgroundNeurofilament light chain (NfL) is a novel biomarker for the assessment of neurological function after cardiac arrest (CA). Although meta-analysis has confirmed its predictive value, it has not conducted a more detailed analysis of its research. We conducted a meta-analysis to evaluate the relationship between serum NfL level and neurological prognosis in patients with spontaneous circulation recovery after CA, and subgroup analysis was conducted according to sample collection time, time to assess neurological function, study design, whether TTM was received, the method of specimen determination, and the presence of neurological disease in patients. To analyze the influence of these factors on the predictive value of serum NfL.MethodsPublished Cochrane reviews and an updated, extended search of MEDLINE, Cochrane Library, Embase, Scopus, ClinicalKey, CINAHL, and Web of Science for relevant studies until March 2022 were assessed through inclusion and exclusion criteria. The standard mean difference and 95% confidence interval were calculated using the random-effects model or fixed-effects model to assess the association between one variable factor NfL level and the outcome of CA patients. Subgroup analysis according to sample collection time was performed. The prognosis analysis and publication bias were also assessed using Egger's and Begg's tests.ResultsAmong 1209 related articles for screening, 6 studies (1360 patients) met the inclusion criteria and were selected for meta-analysis. The level of serum NfL in the good prognosis group (CPC1-2, CPC: cerebral performance category score) was significantly lower than that in the poor prognosis group (CPC3-5)SMD(standardized mean difference) = 0.553, 95%CI(confidence interval) = 0.418-0.687, I2 = 65.5% PConclusionNfL may play a potential neuroprognostication role in postcardiac arrest patients with spontaneous circulation, regardless of when the sample was collected after CA.

The present meta-analysis aimed to investigate the differences in the incidence of thrombosis and vascular compromise in arterial anastomosis between microvascular anastomotic devices and hand-sewn techniques during free tissue transfer in the head and neck. We searched for articles in PubMed/Medline, CNKI, WANFANG DATA, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Web of Science, from January 1, 1962 till April 1, 2020 that reported data of microvascular anastomosis during free tissue transfer in the head and neck. The incidence of arterial thrombosis or vascular compromise, or both was the primary outcome. The secondary outcome was anastomotic time. We also assessed the sensitivity and the risk of bias. This meta-analysis included 583 arterial anastomoses from six studies. The group using microvascular anastomotic devices tended to have an increased incidence of arterial thrombosis and vascular compromise (risk ratio (RR), 3.42; P = 0.38; 95% confidence interval (CI), 0.91-12.77). The hand-sewn technique took significantly longer to perform the anastomosis compared with that of the microvascular anastomotic devices (weighted mean difference, 15.26 min; P

Spent mushroom substrate is made from the waste remaining after the harvest of mushrooms. Here, we evaluated the potential of five spent edible fungi (Auricularia cornea, Lentinus edodes, Pleurotus eryngii, P. citrinopileatus and P. ostreatus) substrates as feed sources for Tenebrio molitor larvae. Young larvae did not survive on any substrate except the spent L. edodes substrate (36.7%). The survival rates in young larvae were similar among the different diets in which wheat bran or rice bran was replaced with 0, 20, 30, 40, 50, or 60% spent L. edodes substrate. The weights of the surviving larvae were decreased only when 70% of wheat bran and > 40% of rice bran was replaced with spent L. edodes substrate. In addition, the middle-aged larvae fed wheat bran only were significantly larger than those fed diets with 30~60% spent L. edodes substrate in dry feed, but the larvae of all treatments failed to pupate. Whereas the green feed was added in dry feed, there were no significant differences in pupal weight, pupation rate, pupal duration, adult emergence, or deformed adults among the three treatments in middle-aged larvae that were fed on diets containing 0, 30, or 40% spent L. edodes substrate. Collectively, these results suggest that spent L. edodes substrate has considerable potential to be used as a partial replacement (< 40%) of conventional feed for T. molitor, and spent mushroom substrate waste may be recycled as feed material for resource insects.

Microglial cells play a key role in brain homeostasis from development to adulthood. Here we show the involvement of a site-specific phosphorylation of Presenilin 1 (PS1) in microglial development. Profiles of microglia-specific transcripts in different temporal stages of development, combined with multiple systematic transcriptomic analysis and quantitative determination of microglia progenitors, indicate that the phosphorylation of PS1 at serine 367 is involved in the temporal dynamics of microglial development, specifically in the developing brain rudiment during embryonic microgliogenesis. We constructed a developing brain-specific microglial network to identify transcription factors linked to PS1 during development. Our data showed that PS1 functional connections appear through interaction hubs at Pu.1, Irf8 and Rela-p65 transcription factors. Finally, we showed that the total number of microglia progenitors was markedly reduced in the developing brain rudiment of embryos lacking PS1 phosphorylation compared to WT. Our work identifies a novel role for PS1 in microglial development.

The mesoscale eddies off the coast of Chile significantly impact the distribution of local chlorophyll and the development of marine ecosystem. Multiple processes, including eddy trapping, pumping, advection, Ekman-pumping, and submesoscale dynamics, exert their impacts simultaneously on transport of water masses at different distances with respect to the eddy center. The cyclonic (anticyclonic) eddies are generally characterized by upwelling (downwelling) within the eddy, which elevates (depresses) chlorophyll inside the eddy. Outside the eddy periphery, multiple processes are involved simultaneously, but their corresponding influences on chlorophyll are not well identified. In this study, the amplitudes of cyclonic and anticyclonic eddies are distinguished as positive and negative values, respectively. A linear regression method is applied to seek the connection between eddy's amplitude and chlorophyll distribution at different locations w.r.t. the eddy center. The regression slope between eddy amplitude and chlorophyll anomaly is found to be negative in the eddy interior and along the periphery, which gradually changes to positive away from the periphery. The location where the response of chlorophyll to an eddy switches its sign is defined as the transition zone. The location of the transition zone varies with offshore distance and is impacted by topography, such as the presence of islands, which can change the dynamics of eddies. Thus, the distance from eddy center and offshore distance from coast should be taken into consideration when investigating their influences on nutrient transport and chlorophyll distribution.

Pigs have experienced long-term selections, resulting in dramatic phenotypic changes. Structural variants (SVs) are reported to exert extensive impacts on phenotypic changes. We built a high resolution and informative SV map based on high-depth sequencing data from 66 Chinese domestic and wild pigs. We inferred the SV formation mechanisms in the pig genome and used SVs as materials to perform a population-level analysis. We detected the selection signals on chromosome X for northern Chinese domestic pigs, as well as the differentiated loci across the whole genome. Analysis showed that these loci differ between southern and northern Chinese domestic pigs. Our results based on SVs provide new insights into genetic differences in Chinese pigs.

The significance of maternal cholesterol transporting to the fetus under normal as well as pathological circumstances is less understood. The objective of this study was to observe the effects of maternal hypercholesterolemia on placental cholesterol transportation. Human full-time placenta, maternal and venous cord blood were sampled at delivery from the pregnant women with serum total cholesterol (TC) concentrations at third trimester higher than 7.25 mM (n = 19) and the pregnant women with normal TC concentrations (n = 19). Serum lipids and expression of genes related to cholesterol transportation were measured by western blot or real-time PCR. The results indicated that serum TC, high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C) levels were significantly increased, in pregnancies, but decreased in cord blood in hypercholesterolemic group compared to the matched control group. All the subjects were no-drinking, non-smoker, and gestational disease free. The mRNA expression of lipoprotein receptors, including LDLR and VLDLR were significantly increased, while the protein expression of PCSK9 was significantly increased in hypercholesterolemic placenta. In conclusion, maternal hypercholesterolemia might decrease the transportation of cholesterol from mother to fetus because of the high levels of PCSK9 protein expression.

Maternally-derived antibodies (MDAs) can protect offspring against influenza virus infection but may also inhibit active immune responses. To overcome MDA- mediated inhibition, active immunization of offspring with an inactivated H5N1 whole-virion vaccine under the influence of MDAs was explored in mice. Female mice were vaccinated twice via the intraperitoneal (IP) or intranasal (IN) route with the vaccine prior to mating. One week after birth, the offspring were immunized twice via the IP or IN route with the same vaccine and then challenged with a lethal dose of a highly homologous virus strain. The results showed that, no matter which immunization route (IP or IN) was used for mothers, the presence of MDAs severely interfered with the active immune response of the offspring when the offspring were immunized via the IP route. Only via the IN immunization route did the offspring overcome the MDA interference. These results suggest that intranasal immunization could be a suitable inoculation route for offspring to overcome MDA interference in the defense against highly pathogenic H5N1 virus infection. This study may provide references for human and animal vaccination to overcome MDA-induced inhibition.

The Sanjiang Plain has been experienced significant wetland loss due to expanded agricultural activities, and will be potentially restored by the China National Wetland Conservation Action Plan (NWCP) in future. The objective of this study is to evaluate the impact of future climate warming and wetland restoration on wetland CH4 emissions in northeast China. We used an atmosphere-vegetation interaction model (AVIM2) to drive a modified biogeophysical model (CH4MODwetland), and projected CH4 flux variations from the Sanjiang Plain wetlands under different Representative Concentration Pathway scenarios throughout the 21st century. Model validation showed that the regressions between the observed and simulated CH4 fluxes by the modified model produced an R2 of 0.49 with a slope of 0.87 (p

The antibacterial and anti-inflammatory activities, and protective effects of extracts (flavonoid glycosides) of Polygonum capitatum were investigated to detect the evidence for the utilization of the herb in the clinical therapy of gastritis caused by H. pylori. A mouse gastritis model was established using H. pylori. According to treating methods, model mice were random assigned into a model group (MG group), a triple antibiotics group (TG group, clarithromycin, omeprazole and amoxicillin), low/middle/high concentrations of flavonoid glycosides groups (LF, MF and HF groups) and low/middle/high concentrations of flavonoid glycosides and amoxicillin groups (LFA, MFA and HFA groups). A group with pathogen-free mice was regarded as a control group (CG group). The eradicate rates of H. pylori were 100%, 93%, 89% in TG, MFA and HF groups. The serum levels of IFN-gamma and gastrin were higher in a MG group than those from all other groups (P < 0.05). The serum levels of IFN-gamma and gastrin were reduced significantly in LF, MF and HF groups (P < 0.05) while little changes were observed in LFA, MFA and HFA groups. In contrast, the serum levels of IL-4 were lower and higher in MG and CG groups compared with other groups (P

HNF1A (Hepatocyte nuclear factor 1 alpha) is a transcription factor that is known to regulate pancreatic differentiation and maintain homeostasis of endocrine pancreas. Recently, genome-wide association studies have implicated HNF1A as a susceptibility gene for pancreatic cancer. However, the functional significance and molecular mechanism of HNF1A in pancreatic carcinogenesis remains unclear.Using RT-PCR, Western blot and immunohistochemistry methods, we examined HNF1A gene expression in eight pancreatic carcinoma cell lines and in paired tumor and normal tissue samples from patients with resected pancreatic ductal adenocarcinoma. We knocked down the HNF1A gene expression in two cancer cell lines using three siRNA sequences. The impacts on cell proliferation, apoptosis, and cell cycle as well as the phosphorylation of Akt signaling transduction proteins were examined using ATP assay, flow cytometry and Western blot.HNF1A was expressed in three out of eight pancreatic adenocarcinoma cell lines and the level of HNF1A mRNA and protein expression was significantly lower in tumors than in normal adjacent tissues by both RT-PCR and Western Blot analyses. Immunohistochemistry revealed that the level of HNF1A expression was significantly lower in tumor tissues than in non-tumor tissues. Selective blocking of HNF1A by specific siRNA conferred a 2-fold higher rate of cell proliferation, 20% increased S phase and G2 phase cells, and 30-40% reduced apoptosis in pancreatic cancer cell lines. We further demonstrated that HNF1A knockdown activated Akt and its downstream target, the mammalian target of rapamycin (mTOR) in pancreatic cancer cells.These observations provide experimental evidence supporting a possible tumor suppressor role of HNF1A in pancreatic cancer.

Endothelium-derived molecules may be predictive to organ injury. Heat shock protein (HSP) A12B is mainly located in endothelial cells, which can be detected in the plasma of septic patients. Whether it is correlated with prognosis of sepsis remains unclear.Extracellular HSPA12B (eHSPA12B) was determined in plasma of septic mice at 6 h, 12 h, 24 h and 48 h after cecal ligation and puncture (CLP). It was also detected in plasma of patients with severe sepsis, sepsis, systemic inflammatory response syndrome and healthy volunteers. The predictive value for prognosis of severe sepsis was assessed by receiver operating curve (ROC) and Cox regression analyses.eHSPA12B was elevated in plasma of CLP mice at 6 h and peaked at 24 h after surgery. A total of 118 subjects were included in the clinical section, including 66 patients with severe sepsis, 21 patients with sepsis, 16 patients with SIRS and 15 volunteers. Plasma eHSPA12B was significantly higher in patients with severe sepsis than in patients with sepsis, SIRS and volunteers. The level of eHSPA12B was also higher in non-survivals than survivals with severe sepsis. The area under the curve (AUC) of eHSPA12B in predicting death among patients with severe sepsis was 0.782 (0.654-0.909) in ROC analysis, much higher than that of IL-6 and IL-10. Cox regression analysis showed that cardiovascular diseases, IL-6 and eHSPA12B were risk factors for mortality in patients with severe sepsis. Survival curve demonstrated a strikingly significant difference between 28-day survival rates of patients with an eHSPA12B lower or not lower than 1.466 ng/ml.Plasma eHSPA12B is elevated in both septic mice and patients. It may be a good predictor for poor outcome in patients with severe sepsis.

Exposure to microgravity results in post-flight cardiovascular deconditioning and orthostatic intolerance in astronauts. Vascular oxidative stress injury and mitochondrial dysfunction have been indicated in this process. To elucidate the mechanism for this condition, we investigated whether mitochondria regulated NADPH oxidase in hindlimb unweighting (HU) rat cerebral and mesenteric arteries. Four-week HU was used to simulate microgravity in rats. Vascular superoxide generation, protein and mRNA levels of Nox2/Nox4, and the activity of NADPH oxidase were examined in the present study. Compared with control rats, the levels of superoxide increased in cerebral (P

SIRT1, a class III histone deacetylase, acts as a negative regulator for many transcription factors, and plays protective roles in inflammation and atherosclerosis. Transcription factor nuclear factor of activated T cells (NFAT) has been previously shown to play pro-inflammatory roles in endothelial cells. Inhibition of NFAT signaling may be an attractive target to regulate inflammation in atherosclerosis. However, whether NFAT transcriptional activity is suppressed by SIRT1 remains unknown. In this study, we found that SIRT1 suppressed NFAT-mediated transcriptional activity. SIRT1 interacted with NFAT, and the NHR and RHR domains of NFAT mediated the interaction with SIRT1. Moreover, we found that SIRT1 primarily deacetylated NFATc3. Adenoviral over-expression of SIRT1 suppressed PMA and calcium ionophore Ionomycin (PMA/Io)-induced COX-2 expression in human umbilical vein endothelial cells (HUVECs), while SIRT1 RNAi reversed the effects in HUVECs. Moreover, inhibition of COX-2 expression by SIRT1 in PMA/Io-treated HUVECs was largely abrogated by inhibiting NFAT activation. Furthermore, SIRT1 inhibited NFAT-induced COX-2 promoter activity, and reduced NFAT binding to the COX-2 promoter in PMA/Io-treated HUVECs. These results suggest that suppression of NFAT transcriptional activity is involved in SIRT1-mediated inhibition of COX-2 expression induced by PMA/Io, and that the negative regulatory mechanisms of NFAT by SIRT1 may contribute to its anti-inflammatory effects in atherosclerosis.