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Abstract Background Multiple vaccinations have received approval for the prevention of the coronavirus illness. Nevertheless, the sluggish vaccination rate is mostly attributed to the general population’s limited understanding and unwillingness to accept the use of vaccinations. Thus, it is important to investigate the Rwandan population’s knowledge, attitudes, and perceptions toward COVID-19 vaccines. Methods A cross-sectional survey was conducted among 370 participants from 11th to 17th February 2023. Demographic information was gathered, and knowledge, attitudes, and perceptions of COVID-19 vaccinations were assessed. A binary logistic regression analysis was undertaken to determine the parameters that determine the perception of COVID-19 vaccinations. Results This study included 370 participants. Among them, 85% had good knowledge about COVID-19 vaccines, and 84% had a positive attitude towards them. Additionally, the study had a diverse group, with half of the participants being female and nearly half falling between the ages of 30 and 39. Several key findings emerged through logistic regression analysis. Those aged 30–39 had 1.39 times higher odds of positive perception than 18–28 (OR = 1.39, 95% CI = 1.08–3.24). Participants with a university education were twice as likely to have a positive perception compared to those without an education level (OR = 2.43, 95% CI = 1.30–6.20). Additionally, single individuals were three times more likely to have a positive perception than their married counterparts (OR = 3.39, 95% CI = 1.28–9.09). Vaccinated individuals had twice the odds of positive perception than non-vaccinated individuals (OR = 2.89, 95% CI = 1.01–8.89). Those receiving information from government health institutions were three times more likely to have a positive perception than those who received the information from friends (OR = 3.19, 95% CI = 1.02–12.7). Moreover, employed participants were four times more likely to have a positive perception non-employed individuals (OR = 4.21, 95% CI = 1.48–13.6). Besides, gender and COVID-19 diagnosis did not significantly correlate with positive COVID-19 vaccine perception. Conclusion The results indicate that the general public in Rwanda has good knowledge, positive attitudes, and a positive perception toward the COVID-19 vaccination, however, some of the participants had some misconceptions towards COVID-19. The findings of this study will be valuable for policymakers and healthcare authorities working to improve vaccination rates.

Abstract Background Dysregulation of enhancer transcription occurs in multiple cancers. Enhancer RNAs (eRNAs) are transcribed products from enhancers that play critical roles in transcriptional control. Characterizing the genetic basis of eRNA expression may elucidate the molecular mechanisms underlying cancers. Methods Initially, a comprehensive analysis of eRNA quantitative trait loci (eRNAQTLs) was performed in The Cancer Genome Atlas (TCGA), and functional features were characterized using multi-omics data. To establish the first eRNAQTL profiles for colorectal cancer (CRC) in China, epigenomic data were used to define active enhancers, which were subsequently integrated with transcription and genotyping data from 154 paired CRC samples. Finally, large-scale case-control studies (34,585 cases and 69,544 controls) were conducted along with multipronged experiments to investigate the potential mechanisms by which candidate eRNAQTLs affect CRC risk. Results A total of 300,112 eRNAQTLs were identified across 30 different cancer types, which exert their influence on eRNA transcription by modulating chromatin status, binding affinity to transcription factors and RNA-binding proteins. These eRNAQTLs were found to be significantly enriched in cancer risk loci, explaining a substantial proportion of cancer heritability. Additionally, tumor-specific eRNAQTLs exhibited high responsiveness to the development of cancer. Moreover, the target genes of these eRNAs were associated with dysregulated signaling pathways and immune cell infiltration in cancer, highlighting their potential as therapeutic targets. Furthermore, multiple ethnic population studies have confirmed that an eRNAQTL rs3094296-T variant decreases the risk of CRC in populations from China (OR = 0.91, 95%CI 0.88–0.95, P = 2.92 × 10−7) and Europe (OR = 0.92, 95%CI 0.88–0.95, P = 4.61 × 10−6). Mechanistically, rs3094296 had an allele-specific effect on the transcription of the eRNA ENSR00000155786, which functioned as a transcriptional activator promoting the expression of its target gene SENP7. These two genes synergistically suppressed tumor cell proliferation. Our curated list of variants, genes, and drugs has been made available in CancereRNAQTL ( http://canernaqtl.whu.edu.cn/#/ ) to serve as an informative resource for advancing this field. Conclusion Our findings underscore the significance of eRNAQTLs in transcriptional regulation and disease heritability, pinpointing the potential of eRNA-based therapeutic strategies in cancers.

Background CDK4 is highly expressed and associated with poor prognosis and decreased survival in advanced neuroblastoma (NB). Targeting CDK4 degradation presents a potentially promising therapeutic strategy compared to conventional CDK4 inhibitors. However, the autophagic degradation of the CDK4 protein and its anti-proliferation effect in NB cells has not been mentioned.Results We identified autophagy as a new pathway for the degradation of CDK4. Firstly, autophagic degradation of CDK4 is critical for NVP-BEZ235-induced G0/G1 arrest, as demonstrated by the overexpression of CDK4, autophagy inhibition, and blockade of autophagy-related genes. Secondly, we present the first evidence that p62 binds to CDK4 and then enters the autophagy-lysosome to degrade CDK4 in a CTSB-dependent manner in NVP-BEZ235 treated NB cells. Similar results regarding the interaction between p62 and CDK4 were observed in the NVP-BEZ235 treated NB xenograft mouse model.Conclusions Autophagic degradation of CDK4 plays a pivotal role in G0/G1 cell cycle arrest in NB cells treated with NVP-BEZ235.

Abstract Background Haemaphysalis concinna, carrying multiple pathogens, has attracted increasing attention because of its expanded geographical range and significant role in disease transmission. This study aimed to identify the potential public health risks posed by H. concinna and H. concinna-associated pathogens. Methods A comprehensive database integrating a field survey, literature review, reference book, and relevant websites was developed. The geographical distribution of H. concinna and its associated pathogens was illustrated using ArcGIS. Meta-analysis was performed to estimate the prevalence of H. concinna-associated microbes. Phylogenetic and geographical methods were used to investigate the role of birds in the transmission of H. concinna-associated microbes. The potential global distribution of H. concinna was predicted by ecological niche modeling. Results Haemaphysalis concinna was distributed in 34 countries across the Eurasian continent, predominantly in China, Russia, and Central Europe. The tick species carried at least 40 human pathogens, including six species in the Anaplasmataceae family, five species of Babesia, four genospecies in the complex Borrelia burgdorferi sensu lato, ten species of spotted fever group rickettsiae, ten species of viruses, as well as Francisella, Coxiella, and other bacteria. Haemaphysalis concinna could parasitize 119 host species, with nearly half of them being birds, which played a crucial role in the long-distance transmission of tick-borne microbes. Our predictive modeling suggested that H. concinna could potentially survive in regions where the tick has never been previously recorded such as central North America, southern South America, southeast Oceania, and southern Africa. Conclusions Our study revealed the wide distribution, broad host range, and pathogen diversity of H. concinna. Authorities, healthcare professionals, and the entire community should address the growing threat of H. concinna and associated pathogens. Tick monitoring and control, pathogen identification, diagnostic tools, and continuous research should be enhanced. Graphical Abstract

Abstract Background Haemaphysalis longicornis is drawing attentions for its geographic invasion, extending population, and emerging disease threat. However, there are still substantial gaps in our knowledge of viral composition in relation to genetic diversity of H. longicornis and ecological factors, which are important for us to understand interactions between virus and vector, as well as between vector and ecological elements. Results We conducted the meta-transcriptomic sequencing of 136 pools of H. longicornis and identified 508 RNA viruses of 48 viral species, 22 of which have never been reported. Phylogenetic analysis of mitochondrion sequences divided the ticks into two genetic clades, each of which was geographically clustered and significantly associated with ecological factors, including altitude, precipitation, and normalized difference vegetation index. The two clades showed significant difference in virome diversity and shared about one fifth number of viral species that might have evolved to “generalists.” Notably, Bandavirus dabieense, the pathogen of severe fever with thrombocytopenia syndrome was only detected in ticks of clade 1, and half number of clade 2-specific viruses were aquatic-animal-associated. Conclusions These findings highlight that the virome diversity is shaped by internal genetic evolution and external ecological landscape of H. longicornis and provide the new foundation for promoting the studies on virus-vector-ecology interaction and eventually for evaluating the risk of H. longicornis for transmitting the viruses to humans and animals. Video Abstract

This paper addresses the critical challenge of effective resource allocation in emergency logistics distribution, particularly during disaster scenarios where demand is uncertain and traditional deterministic optimization methods are inadequate. We propose a novel multi-objective chance-constrained model that minimizes transportation deviation, creating a computationally feasible deterministic equivalent model using uncertainty theory. Furthermore, this paper introduces a hybrid of the Estimation of Distribution Algorithm and the Multi-Objective Snow Goose Algorithm (EDA-MOSGA), designed to efficiently navigate the solution space and identify near-optimal solutions. The EDA-MOSGA enhances Pareto front diversity with its adaptive population adjustment and specialized operator model, marking a significant advancement over existing methods. Validated through the Zitzler-Deb-Thiele (ZDT) and Deb-Thiele-Laumanns-Zitzler (DTLZ) multi-objective test suites, and a case study during the Coronavirus Disease 2020 (COVID) pandemic in Chengdu, the EDA-MOSGA demonstrates exceptional performance in real-world applications. The results of this study lay the foundation for the future integration of artificial intelligence technology to improve the scalability of logistics distribution in different emergency situations.

Abstract Background Malaria remains a significant public health concern in Niger, with the number of cases increasing from 592,334 in 2000 to 3,138,696 in 2010. In response, a concerted campaign against the disease has been initiated. However, the implementation of these malaria interventions and their association with epidemiological behaviour remains unclear. Methods A time-series study was conducted in Niger from 2010 to 2019. Multiple data sources concerning malaria were integrated, encompassing national surveillance data, Statistic Yearbook, targeted malaria control interventions, and meteorological data. Incidence rate, mortality rate, and case fatality ratio (CFR) by different regions and age groups were analysed. Joinpoint regression models were used to estimate annual changes in malaria. The changes in coverage of malaria interventions were evaluated. Results Between 2010 to 2019, the incidence rate of malaria decreased from 249.43 to 187.00 cases per 1,000 population in Niger. Niamey had a high annual mean incidence rate and the lowest CFR, while Agadez was on the contrary. Joinpoint regression analysis revealed a declining trend in malaria incidence for all age groups except the 10–24 years group, and the mortality rate and the CFR initially decreased followed by an increase in all age groups. Niger has implemented a series of malaria interventions, with the major ones being scaled up to larger populations during the study period. Conclusions The scale-up of multi-interventions in Niger has significantly reduced malaria incidence, but the rise in mortality rate and CFR addresses the challenges in malaria control and elimination. Malaria endemic countries should enhance surveillance of malaria cases and drug resistance in Plasmodium, improve diagnosis and treatment, expand the population coverage of insecticide-treated bed nets and seasonal malaria chemoprevention, and strengthen the management of severe malaria cases.

Abstract There has been increasing global concern about the spillover transmission of pangolin-associated microbes. To assess the risk of these microbes for emergence as human pathogens, we integrated data from multiple sources to describe the distribution and spectrum of microbes harbored by pangolins. Wild and trafficked pangolins have been mainly recorded in Asia and Africa, while captive pangolins have been reported in European and North American countries. A total of 128 microbes, including 92 viruses, 25 bacteria, eight protists, and three uncharacterized microbes, have been identified in five pangolin species. Out of 128 pangolin-associated microbes, 31 (including 13 viruses, 15 bacteria, and three protists) have been reported in humans, and 54 are animal-associated viruses. The phylogenetic analysis of human-associated viruses carried by pangolins reveals that they are genetically close to those naturally circulating among human populations in the world. Pangolins harbor diverse microbes, many of which have been previously reported in humans and animals. Abundant viruses initially detected in pangolins might exhibit risks for spillover transmission.

Anaplasma capra is an emerging tickborne human pathogen initially recognized in China in 2015; it has been reported in ticks and in a wide range of domestic and wild animals worldwide. We describe whole-genome sequences of 2 A. capra strains from metagenomic sequencing of purified erythrocytes from infected goats in China. The genome of A. capra was the smallest among members of the genus Anaplasma. The genomes of the 2 A. capra strains contained comparable G+C content and numbers of pseudogenes with intraerythrocytic Anaplasma species. The 2 A. capra strains had 54 unique genes. The prevalence of A. capra was high among goats in the 2 endemic areas. Phylogenetic analyses revealed that the A. capra strains detected in this study were basically classified into 2 subclusters with those previously detected in Asia. Our findings clarify details of the genomic characteristics of A. capra and shed light on its genetic diversity.

With the development of posterior chamber phakic intraocular lenses implantation and the constant improvement of the implantable collamer lens(ICL), ICL V4c implantation has become one of the main methods for correcting moderate and high myopia. Vault is an important indicator to evaluate the security of posterior chamber intraocular lens implantation. In recent years, optimizing surgical procedures to obtain the ideal vault in ICL V4c implantation surgery has become a research hotspot. This paper aims to provide help for improving surgical safety by summarizing and analyzing the optimized programs of ICL V4c implantation surgery. The focus will be on preoperative examination, intraoperative surgical design, and postoperative follow-up.

This paper proposes a multi-objective Gannet Optimization Algorithm (MOGOA) to address the issue of unbalanced train occupancy rates in railway train operation planning. MOGOA employs an adaptive multi-population co-evolutionary strategy to balance exploration and exploitation, utilizing a non-dominated sorting algorithm based on crowding distance to select parent and child samples. These samples serve as initial solutions for subsequent iterations. A novel maximin fitness function guides the iterative update of the global optimal position. MOGOA is applied to the train operation planning problem with dynamic passenger flow allocation feedback. It collaboratively optimizes the number of train operations, sections, and stops to reduce costs, balance occupancy rates, minimize travel time, and enhance travel satisfaction. The practical applicability of MOGOA in optimizing train operation plans based on dynamic passenger flow allocation is significant.

AIM:To observe the early variation trend of the vault after phakic posterior chamber implantable collamer lens/toric implantable collamer lens(ICL/TICL V4c)implantation and analyze the related influencing factors.METHODS:In this retrospective study, a total of 49 patients(98 eyes)who underwent ICL/TICL V4c implantation in the Lanzhou Huaxia Eye Hospital from October 2020 to March 2021 were enrolled. Preoperative ocular biometric parameters were collected, including spherical equivalent(SE), intraocular pressure, axial length, anterior chamber depth(ACD), lens thickness(LT), central corneal thickness, anterior chamber angle(ACA), anterior chamber volume(ACV), white to white corneal diameter(WTW), mean keratometry K1 and K2, and intraoperative implantation size of ICL. The vault was measured by anterior segment optical coherence tomography(AS-OCT)at 1, 3d, 1wk and 1mo after surgery. The patients were divided into insufficient vault group(750μm, 24 eyes)according to the vault at 1mo after surgery. The factors affecting the postoperative vault were analyzed.RESULTS:The mean vault values at 1 and 3d, 1wk and 1mo after surgery were 591.05±293.44, 599.62±309.78, 592.22±301.49 and 586.69±285.63μm, respectively. There were significant differences in WTW, ACA, ACV, ACD, ICL size and LT at 1mo after surgery(all P

For a hundred years the Saint Jacques area has been known to produce rich Oligocene vertebrate fossils, yet only a handful of previous studies have focused on this area. Since 2010, we have conducted 12 field expeditions to Saint Jacques, and here we report findings from our paleontological excavations and stratigraphical investigations. Twenty-two fossiliferous blocks across the area are recognized and a chronostratigraphic framework has been established to aid fossil collection. Fossil-mammal materials have been recovered in situ from 1635 localities and additionally from surface sediments. Fossiliferous blocks in the area are correlated by lithological similarity and lateral tracing. Lithologically, the area is mainly composed of reddish silty mudstone and muddy siltstone, with three distinctive layers of grayish white sandstone. The measured composite stratigraphic column spans 239 meters and are divided into 12 lithostratigraphic units. Contrary to previous knowledge that Saint Jacques contains two Oligocene mammalian assemblages, our preliminary biostratigraphic analysis of small mammals shows that the area documents successive faunal transition from the Eocene to possibly the early Miocene. The hyracodontid perissodactyl Ardynia, the ctenodactyloid rodent Gobiomys, and the basal Glires Gomphos from the bottom litho-units imply the presence of the Eocene–Oligocene boundary, while small mammal assemblage of the top units is similar to Miocene faunas in northern China and Mongolia. Thus, rock strata in Saint Jacques likely span the Eocene through the early Miocene, bracketing an entire Oligocene sequence within. In sum, our re-exploration of Saint Jacques has greatly expanded the chronostratigraphic and taxonomic coverage of the mammalian fossil collection from this area. This long, successive Oligocene sequence makes an important record for studying the Eocene–Oligocene Transition. Further study in this area will contribute to a range of paleontological and paleoenvironmental questions.

Abstract Background Dysregulation of T cells mediated immune responses is a hallmark in the development of systemic lupus erythematosus (SLE). Recent genome wide association study (GWAS) revealed the genetic contribution of variants located in the cytotoxic T lymphocyte-associated protein-4 (CTLA4)-inducible T cell co-stimulator (ICOS) intergenic region to SLE susceptibility. Our aim is to find a functional variant in this region. Methods The genetic association results in the CTLA4-ICOS region from previous GWAS were adopted to select the potential variant which was further replicated in two independent cohorts (Henan cohort 2053 SLE patients and 1845 healthy controls, Beijing cohort 2303 SLE patients and 19,262 healthy). In order to explore the functional significance in SLE, bioinformatics with validation experiments (including electrophoretic mobility shift assay and luciferase reporter assay) and mRNA expression analysis were also performed. Results A variant located in the CTLA4-ICOS intergenic region, rs17268364, was associated with susceptibility to SLE patients in Chinese populations (risk allele, p meta = 7.02×10−11, OR 1.19, 95%CI 1.13–1.26). The bioinformatics suggested that rs17268364 might affect the expression of CTLA4, not ICOS. The rs17268364 risk G allele containing sequence reduced the expression of the reporter gene by binding transcriptional repressor Ewing sarcoma breakpoint region 1 (EWSR1). Following genotype-mRNA expression, the analysis also showed the risk allele of rs17268364 was associated with low CTLA4 expression in lupus nephritis (LN) patients. Healthy individuals carrying rs17268364 risk G allele was significantly correlated with higher levels of IFN-α signature including increased lymphocyte antigen 6E (LY6E) (p=0.031), interferon-stimulated gene 15 (ISG15) (p=0.038), interferon regulatory factor 9 (IRF9) (p=0.028), and interferon regulatory factor 5 (IRF5) (p=0.040) mRNA expression. Conclusions The present study confirmed the functional role of rs17268364 in the CTLA4-ICOS intergenic region that increased SLE susceptibility in the Chinese population.

Culture in temporary immersion systems (TIS) is a valuable tool for the semi-automation of high frequency somatic embryogenesis of coffee. This system allows the intermittent exposure of explants to liquid medium in cycles of specific frequency and duration of immersion with renewal of the culture atmosphere in each cycle. TIS have revolutionized somatic embryogenesis of coffee plants as an alternative for scaling up and reducing costs associated with labor-intensive solid media culture. In Central America, somatic embryogenesis is employed on a commercial scale to produce F1 Coffea arabica hybrids. In Asia and Africa, somatic embryogenesis is used for the multiplication of selected genotypes of C. arabica and C.canephora. Somatic embryogenesis of coffee plants is considered a model system for woody species due to its biological versatility and low frequency of somaclonal variation. Nevertheless, the success of somatic embryogenesis for mass propagation of coffee plants depends on the development, optimization, and transfer of complementary technologies. Temporary immersion using the RITA® bioreactor is, so far, the best complementary tool for somatic embryogenesis of Arabica coffee for a single recipient with simple changes in liquid media. Likewise, high volume bioreactors, such as 10-L glass BIT® and 10-L flexible disposable plastic bags, have been successfully used for somatic embryogenesis of other coffee species. These bioreactors allow the manipulation of thousands of embryos under semi-automated conditions. The protocols, advantages, and benefits of this technology have been well documented for organogenesis and somatic embryogenesis pathways. However, adaptation in commercial laboratories requires technical and logistical adjustments based on the biological response of the cultures as well as the costs of implementation and production. This review presents the historical and present background of TIS and its commercial application and, in particular, pertinent information regarding temporary immersion culture for C. arabica somatic embryogenesis. The main limitations of this technology, such as hyperhydricity, asynchrony, and developmental abnormalities, are examined, and a critical analysis of current knowledge regarding physiological, biochemical, and molecular aspects of the plant response to temporary immersion is offered. Further, perspectives are provided for understanding and solving the morpho-physiological problems associated with temporary immersion culture of coffee plants.Systematic Review Registration:

Abstract Systemic lupus erythematosus (SLE) is a typical autoimmune disease with a strong genetic disposition. Genetic studies have revealed that single-nucleotide polymorphisms (SNPs) in zinc finger protein (ZNF)-coding genes are associated with susceptibility to autoimmune diseases, including SLE. The objective of the current study was to evaluate the correlation between ZNF76 gene polymorphisms and SLE risk in Chinese populations. A total of 2801 individuals (1493 cases and 1308 controls) of Chinese Han origin were included in this two-stage genetic association study. The expression of ZNF76 was evaluated, and integrated bioinformatic analysis was also conducted. The results showed that 28 SNPs were associated with SLE susceptibility in the GWAS cohort, and the association of rs10947540 was successfully replicated in the independent replication cohort (P replication = 1.60 × 10−2, OR 1.19, 95% CI 1.03–1.37). After meta-analysis, the association between rs10947540 and SLE was pronounced (P meta = 9.62 × 10−6, OR 1.29, 95% CI 1.15–1.44). Stratified analysis suggested that ZNF76 rs10947540 C carriers were more likely to develop relatively high levels of serum creatinine (Scr) than noncarriers (CC + CT vs. TT, p = 9.94 × 10−4). The bioinformatic analysis revealed that ZNF76 rs10947540 was annotated as an eQTL and that rs10947540 was correlated with decreased expression of ZNF76. Remarkably, significantly reduced expression of ZNF76 was confirmed by expression data from both our laboratory and an array-based expression database. Taken together, these results suggest that ZNF76 rs10947540 is a possible susceptibility factor associated with SLE susceptibility. The mechanism underlying the relationship between ZNF76 and SLE pathogenesis still requires further investigation.

Abstract Background Eimeria tenella is a highly pathogenic coccidian that causes avian coccidiosis. Both nitromezuril (NZL) and ethanamizuril (EZL) are novel triazine compounds with high anticoccidial activity, but the mechanisms of their action are still unclear. This study explored the response of E. tenella to NZL and EZL by the study of changes in protein composition of the second-generation merozoites. Methods Label-free quantification (LFQ) proteomics of the second-generation merozoites of E. tenella following NZL and EZL treatment were studied by LC-MS/MS to explore the mechanisms of action. The identified proteins were annotated and analyzed by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and protein-protein interaction (PPI) networks analysis. Results A total of 1430 proteins were identified by LC-MS/MS, of which 375 were considered as differential proteins in response to drug treatment (DPs). There were 26 only found in the NZL treatment group (N-group), 63 exclusive to the EZL treatment group (E-group), and 80 proteins were present in both drug groups. In addition, among the DPs, the abundant proteins with significantly altered expression in response to drug treatment (SDPs) were found compared with the C-group, of which 49 were upregulated and 51 were downregulated in the N-group, and 66 upregulated and 79 downregulated in the E-group. Many upregulated proteins after drug treatment were involved in transcription and protein metabolism, and surface antigen proteins (SAGs) were among the largest proportion of the downregulated SDPs. Results showed the top two enriched GO terms and the top one enriched pathway treated with EZL and NZL were related, which indicated that these two compounds had similar modes of action. Conclusions LFQ proteomic analysis is a feasible method for screening drug-related proteins. Drug treatment affected transcription and protein metabolism, and SAGs were also affected significantly. This study provided new insights into the effects of triazine anticoccidials against E. tenella.

Ethanamizuril (EZL) is a novel triazine anticoccidial compound that has high anticoccidial activity in chickens. In order to treat coccidiosis rationally in poultry, a detection method was developed for ethanamizuril in broiler plasma, and then the pharmacokinetics studies were performed in broilers after oral administration of different dose levels. Ethanamizuril was administered as single oral doses at low (0.67 mg kg−1 BW), medium (1.33 mg kg−1 BW) and high (6.67 mg kg−1 BW) levels in which the medium dose was that recommended in clinics. Plasma concentrations of ethanamizuril were determined using ultra-high performance liquid chromatography and the data were analyzed with a non-compartmental model. Peak plasma concentrations of ethanamizuril were (2.16±0.57), (3.91±0.71), and (23.71±5.02) mg L−1 at (5.17±1.80), (4.60±2.12), and (4.60±2.12) h, respectively. The terminal elimination half-lives (t1/2λz) for ethanamizuril were (10.84±2.59), (10.66±2.47), and (13.34±3.10) h after oral administration at low, medium and high doses, respectively. The areas under the concentration-time curve (AUC0–t) were (37.68±6.87), (73.19±9.18), and (485.76±125.10) mg L−1 h with mean residence times (MRT0–t) of (14.79±3.03), (15.57±3.69), and (20.22±4.01) h at the 3 dosages, respectively. Ethanamizuril was absorbed rapidly and eliminated slowly. A comparison across the dose range indicated that the time to reach peak plasma concentration (Tmax) values were similar while peak plasma concentration (Cmax) and AUC0–t were positively correlated with increasing dosages. This study of the pharmacokinetics of an ethanamizuril solution in chickens provides a theoretical basis for the rational use in the clinic.

A recent genome-wide association study (GWAS) of Asian ancestry reported that single nucleotide polymorphism (SNP) in TERT (telomerase reverse transcriptase) was associated with systemic lupus erythematosus (SLE). TERT has a critical role in maintaining the chromosomal stability and the length of telomere. Given that only a small portion of the genetic heritability of SLE has been explained so far, we aimed to identify novel loci in telomere-related genes responsible for SLE susceptibility in Chinese populations. We performed a comprehensive genetic association analysis of SLE with telomere-related genes. To identify functional significance, we analyzed the publicly available HaploReg v4.1 and RegulomeDB databases. Differential gene expression analysis was also performed using ArrayExpress. A novel signal of PINX1 rs6984094 was identified (Pdiscovery=4.13×10−2, OR=0.58, 95% CI 0.35-0.98) and successfully replicated (Preplication=5.73×10−3, OR=0.45, 95% CI 0.26-0.81). Multiple layers of functional analysis suggested that the PINX1 rs6984094 risk T allele exhibited increased nuclear protein binding. We also observed an increased expression of PINX1 mRNA in peripheral blood mononuclear cells from SLE patients compared with healthy controls. Overall, we observed a novel genetic association between PINX1 (encodes the PinX1 protein, an inhibitory telomerase enzyme that lengthens telomeres) and SLE susceptibility in Chinese populations.

Background. Systemic lupus erythematosus (SLE) is a complex autoimmune disease with strong genetic disposition with more than 100 susceptibility genes identified until now. However, our knowledge on SLE genetic background is still limited. The present study was aimed at evaluating the role of single nucleotide polymorphisms (SNPs) in SCUBE3, a TGF-β signaling activator, with SLE susceptibility in Chinese populations. Methods. A total of 2801 individuals (490 cases and 493 controls from GWAS cohort and 1003 cases and 815 controls from our cohort) were enrolled, and SNPs located 10 kb up- and downstream of SCUBE3 (chr6:35182190-35218609) were included in the genetic association study. Multiple layers of bioinformatics were conducted, and the levels of SCUBE3 expression were confirmed. Results. Of the 31 SNPs in SCUBE3 tested, 24 SNPs were significantly associated with SLE at p≤0.05. The top locus was rs1888822 with p=8.74∗10−6 in the discovery cohort and was confirmed by the replication cohort with p=0.012. Additionally, the levels of SCUBE3 mRNA expression were significantly lower in patients with SLE comparing with healthy controls (p=4.28∗10−4). Further expression data from ArrayExpress showed that the expression of SCUBE3 was also lower in CD3+ T cells and B cells from patients with SLE. Conclusions. Our research revealed that variants in SCUBE3, which encode SCUBE3 as a TGF-β signaling activator, can be considered as a new genetic susceptibility factor for systemic lupus erythematosus. And the reduced mRNA expression of SCUBE3 was first reported in patients with SLE.

The data in this paper are related to the research article entitled “Taxonomic status and phylogenetic relationship of tits based on mitogenomes and nuclear segments” (X.J. Li et al., 2016) [1]. The mitochondrial genomes and nuclear segments of tits were sequenced to analyze mitochondrial characteristics and phylogeny. In the data, the analyzed results are presented. The data holds the resulting files of mitochondrial characteristics, heterogeneity, best schemes, and trees.

Since more and more third-party Android applications integrate backup services, the security issues of mobile backup modules are critical. By studying how widely these backup services were being used in the Android applications, the differences of code security about four mainstream Android backup SDK were investigated. After analyzing and comparing the usages, protocols and API functions of these SDK. Based on the above findings and three reported security issues of mobile backup services, the countermeasures for third-party application developers were suggested to securely call the SDK of mobile backup services.

Abstract Objectives Interleukin‐33, a newly identified member of interleukin‐1 family, had been confirmed to play a crucial role in regulating inflammatory responses in various disease. However, the exact role of interleukin‐33 in the disease process of acute ischemic stroke still remains unclear. This study aims to demonstrate the relationship between interleukin‐33 levels and long‐term functional outcome as well as ischemic stroke recurrence. Methods Three hundred and four first‐ever acute ischemic stroke patients were recruited and basic information and history of all subjects taken within 72 hr on admission. The functional outcome was estimated by Barthel index. The multivariate logistic regression was used to analyze the prognosis, while the Cox proportional hazard model was applied to assess the recurrence risk. Results Out of 304 subjects, 259 patients successfully completed scheduled two‐year follow‐up. We found that higher interleukin‐33 levels correlated positively with better prognosis as compared with those with lower interleukin‐33 levels who presented with poorer outcome (62.45 ± 20.50 ng/ml vs. 51.58 ± 19.16 ng/ml, p

A rapid, sensitive and specific ultra-high-performance liquid chromatography tandem mass spectrometry (UPLC-MS) method was developed for the analysis of tetracycline antibiotics, including tetracycline (TC), oxytetracycline (OTC), chlortetracycline (CTC) and their 4-epimers (4-epiTCs) in agricultural soil fertilized with swine manure. Soil samples were extracted and cleaned-up with 10 mL EDTA-McIlvaine buffer solution (pH 4.0), then cleaned-up and pre-concentrated using the Oasis MAX cartridge and then eluted with 1 mL solution by mixing formic acid, methanol and water at a ratio of 2:15:83 (v/v/v). The purified samples were separated by an ACQUITY UPLC BEH C18 column using acetonitrile and water containing 0.1% formic acid mobile phase and detected by a single quadrupole MS. The limits of detection for the soil extraction method (LODsoil) ranged from 0.6-2.5 μg kg−1 with recoveries from 23.3-159.2%. Finally, the method was applied to an agricultural field in an area with intensive pig-fattening farming. Tetracyclines were detected in soil from 2.8 to 42.4 μg kg−1 soil. These results demonstrate that soil from swine farms can become severely contaminated with tetracycline antibiotics and their metabolites.

Five previously undescribed triterpenoid saponins (1–5), along with eight known ones (6–13), were isolated from the whole plants of Anemone rivularis var. flore-minore. Their structures were clarified by extensive spectroscopic data and chemical evidence. For the first time, the lupane-type saponins (3 and 12) were reported from the Anemone genus. The anti-proliferative activity of all isolated saponins was evaluated on hepatic stellate cells (HSC-T6). Saponins 12 and 13, which possess more monosaccharides than the others, displayed potent anti-proliferative activity, with IC50 values of 18.21 and 15.56 μM, respectively.