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Beam energy, normalized emittance, and quantum efficiency are crucial parameters of the RF gun. In this study, we proposed a compact and low-cost method to measure the beam energy at the exit of the 120 MeV electron linac's RF gun. We utilized a solenoid magnetic field to rotate an elliptical beam and measured the rotation angle of the beam to calculate the energy. To generate an elliptical electron beam, we inserted a slit device after the laser beam shaping aperture (BSA) to produce a long strip of driving laser beam for the RF gun photocathode. During the measurement process, we employed the Maximally Stable Extremal Regions (MSER) detection algorithm to measure the beam spot angle, improving the accuracy and stability of the angle measurement. This method does not require any changes to the accelerator lattice, nor does it require additional space. It only requires inserting a slit device to measure the beam's energy. Our results indicated that the energy at the exit of the RF gun was 4-5 MeV, consistent with simulation calculations using ASTRA.

The underground logistics system is a relatively new concept for container transportation, which is designed to reduce the congestion and pollution on the road caused by the sharply growing number of collections and distributions of containers in the port cities. This paper considers a system where some underground logistics vehicles (ULVs) are marshaled and used to transport containers between two port terminals through a deep underground tunnel. Automated guided vehicles (AGVs) are used for horizontal transportation of containers in the above-ground yard of the terminals, and yard cranes (YCs) are used to transfer the containers vertically through a shaft linking the above-ground yard and the deep underground tunnel. To guarantee the efficiency of this system, a joint scheduling problem of the YCs and the ULVs is proposed and formulated as an integer programming model to minimize the total waiting time of the YCs and ULVs. Taking marshaling and congestion of the ULVs into consideration, a Genetic Algorithm is developed to solve the problem. Numerical experimental results prove the efficiency of the proposed algorithm, and different marshaling strategies are compared. Our research provides a scientific foundation for developing underground logistics systems in large port cities.

Stochastic and robust optimization approaches often result in sub-optimal solutions for the uncertain p-hub median problem when continuous design parameters are discretized to form different environmental scenarios. To solve this problem, this paper proposes a triangular fuzzy number model for the Non-Strict Uncapacitated Multi-Allocation p-hub Median Problem. To enhance the quality and the speed of optimization, a novel optimization approach, combining the triangular fuzzy number evaluation index with the Genetic-Tabu Search algorithm, is proposed. During the iterations of the Genetic-Tabu Search algorithm for finding the optimal solution, the fitness of fuzzy hub schemes is calculated by considering the relative positional relationships of triangular fuzzy number membership functions. This approach directly addresses the triangular fuzzy number model and ensures the integrity of information in the p-hub problem as much as possible. It is verified by the classic Civil Aeronautics Board and several self-constructed data sets. The results indicate that, compared to the traditional Genetic Algorithm and Tabu Search algorithm, the Genetic-Tabu Search algorithm reduces average computation time by 49.05% and 40.93%, respectively. Compared to traditional random, robust, and real-number-based optimization approaches, the proposed optimization approach reduces the total cost in uncertain environments by 1.47%, 2.80%, and 8.85%, respectively.

BackgroundThere are limited epidemiological investigations of blood metal levels related to hyperlipidemia, and results indicating the association between blood lead (Pb), cadmium (Cd) and selenium (Se), and lipid biomarkers have been conflicting.MethodsWe included populations for which NHANES collected complete data. Multivariate logistic regression and subgroup analyses were conducted to ascertain the relationship between blood Pb, Cd, and Se levels and hyperlipidemia. Nonlinear relationships were characterized by smoothed curve fitting and threshold effect analysis.Results5429 participants in all, with a mean age of 53.70 ± 16.63 years, were included; 47.1% of the subjects were male, and 3683 (67.8%) of them had hyperlipidemia. After modifying for variables with confounders in a multivariate logistic regression model, we discovered a positive correlation between blood Pb and Se levels and hyperlipidemia (Pb: OR:2.12, 95% CI:1.56-2.88; Se: OR:1.84, 95% CI:1.38-2.45). Gender, age, smoking status, alcohol use status, hypertension, diabetes, and body mass index were not significantly linked with this positive correlation, according to subgroup analysis and interaction test (P for interaction>0.05). Positive correlations between blood Pb, Cd, and Se levels and the risk of hyperlipidemia have been found using smooth curve fitting.ConclusionsThis study demonstrates that higher blood levels of Pb, Cd, and selenium are linked to an increased risk of hyperlipidemia.

The pursuit of drugs and methods to safeguard dopaminergic neurons holds paramount importance in Parkinson's disease (PD) research. Benfotiamine (BFT) has demonstrated neuroprotective properties, yet its precise mechanisms in PD remain elusive. This study investigated BFT's potential protective effects against dopamine neuron damage in a PD animal model and the underlying mechanisms. The PD mouse model was induced by 5 consecutive MPTP injections, followed by BFT intervention for 28 days. Motor deficits were assessed via pole test, hang test, gait analysis, and open field test, while dopaminergic neuron damage was evaluated through Immunofluorescence, Nissl staining, and Western blot analysis of Tyrosine Hydroxylase (TH) in the substantia nigra and striatum. High Performance Liquid Chromatography quantified dopamine (DA) levels and its metabolites. Genetic pathways were explored using RNA-seq and bioinformatics analysis on substantia nigra tissues, confirmed by qPCR. Activation of the Nrf2 pathway was examined through nuclear translocation and expression of downstream antioxidant enzymes HO-1, GCLM, and NQO1 at mRNA and protein levels. Additionally, measurements of MDA content, GSH activity, and SOD activity were taken in the substantia nigra and striatum. BFT administration improved motor function and protected against dopaminergic neuron degeneration in MPTP mice, with partial recovery in TH expression and DA levels. RNA-seq analysis revealed distinct effects of BFT and the NLRP3 inhibitor MCC950 on Parkinson-related pathways and genes. Control of Nrf2 proved crucial for BFT, as it facilitated Nrf2 movement to the nucleus, upregulating antioxidant genes and enzymes while mitigating oxidative damage. This study elucidates BFT's neuroprotective effects in a PD mouse model via Nrf2-mediated antioxidant mechanisms and gene expression modulation, underscoring its potential as a therapeutic agent for PD.

The interaction of PD-L1 with PD-1 is a major immune checkpoint that limits effector T cell function against cancer cells; monoclonal antibodies that block this pathway have been approved in multiple tumor indications. As a next generation therapy, small molecule inhibitors of PD-L1 have inherent drug properties that may be advantageous for certain patient populations compared to antibody therapies. In this report we present the pharmacology of the orally-available, small molecule PD-L1 inhibitor CCX559 for cancer immunotherapy. CCX559 potently and selectively inhibited PD-L1 binding to PD-1 and CD80 in vitro, and increased activation of primary human T cells in a T cell receptor-dependent fashion. Oral administration of CCX559 demonstrated anti-tumor activity similar to an anti-human PD-L1 antibody in two murine tumor models. Treatment of cells with CCX559 induced PD-L1 dimer formation and internalization, which prevented interaction with PD-1. Cell surface PD-L1 expression recovered in MC38 tumors upon CCX559 clearance post dosing. In a cynomolgus monkey pharmacodynamic study, CCX559 increased plasma levels of soluble PD-L1. These results support the clinical development of CCX559 for solid tumors; CCX559 is currently in a Phase 1, first in patient, multicenter, open-label, dose-escalation study (ACTRN12621001342808).

Amaranthus retroflexus L. is one of the malignant weeds which can cause a reduction in the soybean yield. We found a population of A. retroflexus (R-Q) resistant to fomesafen through the initial screening of whole-plant dose response bioassay in the research. The resistance index of the population (R-Q) was 183 times of the sensitive population (S-N). The resistant and sensitive populations were used as experimental materials in the paper. Strand-specific RNA-Seq analyses of R‒Q and S‒N populations obtained from herbicide-treated and mock-treated leaf samples after treatment were conducted to generate a full-length transcriptome database. We analyzed differentially expressed genes (DEGs) among the R-Q and S‒N A. retroflexus populations treated with recommended dose and mock-treated on the 1st (24 h) and 3rd (72 h) days to identify genes involved in fomesafen resistance. All 82,287 unigenes were annotated by Blastx search with E-value < 0.00001 from 7 databases. A total of 94,815 DEGs among the three group comparisons were identified. Two nuclear genes encoding PPO (PPX1 and PPX2) and five unigenes belonging to the AP2-EREBP, GRAS, NAC, bHLH and bZIP families exhibited different expression patterns between individuals of S‒N and R-Q populations. The A. retroflexus transcriptome and specific transcription factor families which can respond to fomesafen in resistant and susceptible genotypes were reported in this paper. The PPX1 and PPX2 genes of the target enzyme were identified. The study establishes the foundation for future research and provides opportunities to manage resistant weeds better.

With the rapid advancement of urbanization, the green space well-being (GSWB) of developing countries faces drastic changes and is increasingly threatened. Green and residential spaces are the core elements of GSWB; however, we know very little about the interaction and combination of the two in terms of their effect on GSWB. This study identified the spatiotemporal features of GSWB and critically examined how patterns of residential-green combinations affect GSWB. Based on land-use data for Jinan from 2006 to 2018, and using the spatial measurement tool GeoDa, we found that both green and residential space have increased significantly in central Jinan. At the macro level, the spatial correlation between the two decreased significantly; meanwhile, at the micro level, there are obvious differences in time and geography. This led to differences in the distribution of GSWB between regions with high value and those with low value. We revealed that the development, preservation, and demolition of residential and green spaces influence changes in GSWB. The positive effects on GSWB come from (1) mountain park development policy in built-up areas, (2) theme park development policy in new urban areas, and (3) urban renewal and demolition policy. The negative effects on GSWB come from (1) issues remaining from prior extensive urban development, (2) the replacement of central areas driven by urban branding, and (3) the lack of supervision of nearby facilities for new housing development. To better understand changes in GSWB, it is necessary to consider its internal residential-green spatial collaboration and propose targeted response strategies. This can help to better safeguard the quality of human settlements in the process of urbanization in developing countries.

As consumers' green awareness continues to grow, the level of a product's eco-friendliness and the quality of its marketing have become significant factors in shaping consumers' purchasing decisions. The power structures within the supply chain, as well as corresponding government subsidy policies, are also key elements influencing sustainable strategies for the green supply chain. In a green supply chain comprising one manufacturer and one e-commerce platform, two sales models exist within the online e-commerce platforms: reselling and agency selling. This paper establishes and analyzes three distinct Stackelberg game models, namely: manufacturer-led model without subsidy (bm), manufacturer-led model with subsidy (sm), and platform-led model with subsidy (sp). The results are shown as follows, with the rise of consumers' environmental awareness, more consumers opt for green products, inspiring the manufacturer to increase its optimal greenness and platform to enhance its optimal marketing efforts level. Notably, government subsidies provide a significant stimulus. An increase in the green technology cost coefficient leads to a decline in the manufacturer's profits across all three modes. Intriguingly, the manufacturer's profits are always highest in the sp mode. As the marketing efforts cost coefficient increases, the platform's profits decrease in the bm and sm modes. In contrast, in the sp mode, the platform's profits increase rather than a decrease. The choice of mode primarily depends on the platform's marketing efforts cost coefficient. When this coefficient exceeds a threshold, the platform chooses the sp mode. However, due to the relatively low marketing efficiency in this scenario, the manufacturer prefers the sm mode. For the government, the sp mode involves agency selling, serves as an effective mechanism to redistribute subsidies, thereby yielding the maximum social welfare benefits. Management insights are provided for the manufacturer and platform managers to make decisions about the degree of greenness and marketing efforts level, along with insights for governments to optimize subsidy policies.

The pore structure characteristics and thermal conductivity of foamed concrete (FC) reinforced with glass fibers (GF), polyvinyl alcohol fibers (PVAF) and polypropylene fibers (PPF) were investigated experimentally in this article. Firstly, GF, PVAF or PPF with different mass fractions (0%, 1%, 1.5% and 2%) were added to the Portland cement, fly ash and plant protein foaming agent to prepare the FC. Then, SEM tests, dry density tests, porosity tests, and thermal conductivity tests were carried out on FRFC. Later, the adhesion of GF, PVAF and FFF with different mass fractions to the cementitious base was investigated by SEM images of FRFC. The pore size distribution, shape factor and porosity of FRFC were analyzed using Photoshop software and Image Pro Plus (IPP) software. Finally, the effects of different mass fractions and lengths of three types of fibers on the thermal conductivity of FRFC were discussed. The results indicated that proper fiber mass fraction can play a role of refining small pores and separating large pores, improving the structural compactness, reducing the pore collapse phenomenon and optimizing the pore structure of FRFC. The three types of fibers can promote the optimization of cellular roundness and increase the proportion of pores with diameters below 400 μm. The FC with larger porosity had smaller dry density. As the fiber mass fraction increased, the thermal conductivity performed a phenomenon of first decrease and then increase. The three types of fibers with 1% mass fraction achieved relatively low thermal conductivity. Compared with the FC without fibers, the thermal conductivities of GF reinforced FC, PVAF reinforced FC and PPF reinforced FC with 1% mass fraction were decreased by 20.73%, 18.23% and 7.00%, respectively.

A popular subject of general interest is the connection between corporate social responsibility, research and development, tax policy, and the purchase of green bonds. To encourage the coordinated growth of the economy and a pollution-free environment, it is crucial to understand how they interact. The paper develops a theoretical framework based on the general equilibrium theory's multi-sector model to examine how tax competition affects environmental degradation. The existence of such an effect, which is a threshold effect resulting from corporate social responsibility (CSR), and how it is impacted by CSR are theoretically established. The study used Moroccan province panel data from 2000 to 2022 and the spatial panel threshold model. The empirical finding demonstrates the importance of the threshold impact of CSR since reduced tax competition tends to worsen environmental degradation when CSR is above the threshold value and to reduce it when CSR is below the threshold value. The study also reveals that the impact of tax competitiveness varies regionally. Several policy suggestions are then put out to assist Morocco in reducing environmental pollution through taxation.

An epidemic of Corona Virus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading worldwide. Moreover, the emergence of SARS-CoV-2 variants of concern, such as Delta and Omicron, has seriously challenged the application of current therapeutics including vaccination and drugs. Relying on interaction of spike protein with receptor angiotensin-converting enzymes 2 (ACE2), SARS-CoV-2 successfully invades to the host cells, which indicates a strategy that identification of small-molecular compounds to block the entry is of great significance for COVID-19 prevention. Our study evaluated the potential efficacy of natural compound oxalic acid (OA) as an inhibitory agent against SARS-CoV-2 invasion, particular on the interaction of the receptor binding domain (RBD) of Delta and Omicron variants to ACE2. By employing a competitive binding assay in vitro, OA significantly blocked the binding of RBDs from Delta B.1.617.2 and Omicron B.1.1.529 to ACE2, but has no effect on the wide-type SARS-CoV-2 strain. Furthermore, OA inhibited the entries of Delta and Omicron pseudovirus into ACE2 high expressing-HEK293T cells. By surface plasmon resonance (SPR) assay, the direct bindings of OA to RBD and ACE2 were analyzed and OA had both affinities with RBDs of B.1.617.2 and B.1.1.529 and with ACE2. Molecular docking predicted the binding sites on the RBD-ACE2 complex and it showed similar binding abilities to both complex of variant Delta or Omicron RBD and ACE2. In conclusion, we provided a promising novel small-molecule compound OA as an antiviral candidate by blocking the cellular entries of SARS-CoV-2 variants.

ObjectivesThis study intends to build and compare two kinds of forecasting models at different time scales for hemorrhagic fever incidence in China.MethodsAutoregressive Integrated Moving Average (ARIMA) and Long Short-Term Memory Neural Network (LSTM) were adopted to fit monthly, weekly and daily incidence of hemorrhagic fever in China from 2013 to 2018. The two models, combined and uncombined with rolling forecasts, were used to predict the incidence in 2019 to examine their stability and applicability.ResultsARIMA (2, 1, 1) (0, 1, 1)12, ARIMA (1, 1, 3) (1, 1, 1)52 and ARIMA (5, 0, 1) were selected as the best fitting ARIMA model for monthly, weekly and daily incidence series, respectively. The LSTM model with 64 neurons and Stochastic Gradient Descent (SGDM) for monthly incidence, 8 neurons and Adaptive Moment Estimation (Adam) for weekly incidence, and 64 neurons and Root Mean Square Prop (RMSprop) for daily incidence were selected as the best fitting LSTM models. The values of root mean square error (RMSE), mean absolute error (MAE) and mean absolute percentage error (MAPE) of the models combined with rolling forecasts in 2019 were lower than those of the direct forecasting models for both ARIMA and LSTM. It was shown from the forecasting performance in 2019 that ARIMA was better than LSTM for monthly and weekly forecasting while the LSTM was better than ARIMA for daily forecasting in rolling forecasting models.ConclusionsBoth ARIMA and LSTM could be used to build a prediction model for the incidence of hemorrhagic fever. Different models might be more suitable for the incidence prediction at different time scales. The findings can provide a good reference for future selection of prediction models and establishments of early warning systems for hemorrhagic fever.

We developed a human intracellular antibody based on the M1 protein from avian influenza virus H5N1 (A/meerkat/Shanghai/SH-1/2012) and then characterized the properties of this antibody. The M1 protein sequence was amplified by RT-PCR using the cDNA of the H5N1 virus as a template, expressed in bacterial expression system BL21 (DE3) and purified. A human strain, high affinity, and single chain antibody (HuScFv) against M1 protein was obtained by phage antibody library screening using M1 as an antigen. A recombinant TAT-HuScFv protein was expressed by fusion with the TAT protein transduction domain (PTD) gene of HIV to prepare a human intracellular antibody against avian influenza virus. Further analysis demonstrated that TAT-HuScFv could inhibit the hemagglutination activity of the 300 TCID50 H1N1 virus, thus providing preliminary validation of the universality of the antibody. After two rounds of M1 protein decomposition, the TAT-HuScFv antigen binding site was identified as Alanine (A) at position 239. Collectively, our data describe a recombinant antibody with high binding activity against the conserved sequences of avian influenza viruses. This intracellular recombinant antibody blocked the M1 protein that infected intracellular viruses, thus inhibiting the replication and reproduction of H5N1 viruses.

The current study aimed to explore the lncRNA-miRNA-mRNA networks associated with alcohol-related esophageal cancer (EC). RNA-sequencing and clinical data were downloaded from The Cancer Genome Atlas and the differentially expressed genes (DEGs), long non-coding RNAs (lncRNAs, DELs), and miRNAs (DEMs) in patients with alcohol-related and non-alcohol-related EC were identified. Prognostic RNAs were identified by performing Kaplan-Meier survival analyses. Weighted gene co-expression network analysis was employed to build the gene modules. The lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) networks were constructed based on our in silico analyses using data from miRcode, starBase, and miRTarBase databases. Functional enrichment analysis was performed for the genes in the identified ceRNA networks. A total of 906 DEGs, 40 DELs, and 52 DEMs were identified. There were eight lncRNAs and miRNAs each, including ST7-AS2 and miR-1269, which were significantly associated with the survival rate of patients with EC. Of the seven gene modules, the blue and turquoise modules were closely related to disease progression; the genes in this module were selected to construct the ceRNA networks. SNHG12-miR-1-ST6GAL1, SNHG3-miR-1-ST6GAL1, SPAG5-AS1-miR-133a-ST6GAL1, and SNHG12-hsa-miR-33a-ST6GA interactions, associated with the N-glycan biosynthesis pathway, may have key roles in alcohol-related EC. Thus, the identified biomarkers provide a novel insight into the molecular mechanism of alcohol-related EC.

Food production facilities are often routinely tested over time for the presence of foodborne pathogens (e.g., Listeria monocytogenes or Salmonella enterica subsp. enterica). Strains detected in a single sampling event can be classified as transient; positive findings of the same strain across multiple sampling events can be classified as resident pathogens. We analyzed whole-genome sequence (WGS) data from 4,758 isolates (L. monocytogenes = 3,685; Salmonella = 1,073) from environmental samples taken by FDA from 536 U.S. facilities. Our primary objective was to determine the frequency of transient or resident pathogens within food production facilities. Strains were defined as isolates from the same facility that are less than 50 SNP (single-nucleotide polymorphisms) different from one another. Resident pathogens were defined as strains that had more than one isolate collected >59 days apart and from the same facility. We found 1,076 strains (median = 1 and maximum = 21 strains per facility); 180 were resident pathogens, 659 were transient, and 237 came from facilities that had only been sampled once. As a result, 21% of strains (180/ 839) from facilities with positive findings and that were sampled multiple times were found to be resident pathogens; nearly 1 in 4 (23%) of L. monocytogenes strains were found to be resident pathogens compared to 1 in 6 (16%) of Salmonella strains. Our results emphasize the critical importance of preventing the colonization of food production environments by foodborne pathogens, since when colonization does occur, there is an appreciable chance it will become a resident pathogen that presents an ongoing potential to contaminate product.

The sensitivity of Hypsizygus marmoreus to environmental factors such as temperature, humidity, illumination and CO2 concentration varies greatly in different growth stages. In this paper, the effects of various environmental factors on the growth and development of H. marmoreus were investigated by measuring the enzyme activities of H. marmoreus at different growth stages under different microenvironment conditions in the mushroom room, so as to confirm the influence mechanism of environmental factors on the growth of H. marmoreus. The results showed that at budding stage xylanase and laccase were found significantly positively correlated with CO2 concentration and light intensity, and dramatically negatively correlated with humidity while carboxymethyl cellulose and manganese peroxidase were markedly positively correlated with humidity, and significantly negatively correlated with CO2 concentration and light intensity. On the other hand, in mature fruit bodies xylanase activity was found significantly positively correlated with CO2 concentration and light intensity, and dramatically negatively correlated with humidity while manganese peroxidase activities were found significantly positively correlated with humidity, and dramatically negatively correlated with light intensity. The activity of β-glucosidase in budding and mature fruiting bodies was markedly negatively correlated with CO2 concentration and significantly positively correlated with humidity.

ObjectiveWhen facing major emergency public accidents, men and women may react differently. Our research aimed to assess the influence of gender difference on social support, information preference, biological rhythm, psychological distress, and the possible interaction among these factors during the COVID-19 pandemic.MethodsIn this cross-sectional study, 3,237 respondents aged 12 years and older finished the online survey. Levels of social support, information preference, biological rhythm, and psychological distress were assessed using validated scales. A path analysis was conducted to explore possible associations among these variables.ResultsThe path analysis indicated that women with high levels of social support had a lower possibility of biological rhythm disorders and lower levels of somatization symptoms of psychological distress during the COVID-19 pandemic. The influence of social support on somatization symptoms was exerted via biological rhythm. Women tended to believe both negative and positive information, while men preferred more extreme information.ConclusionOur results highlighted gender difference in study variables during the COVID-19 pandemic and the importance of social support in alleviating psychological distress and biological rhythm disorders. Moreover, we confirmed that information preference differed significantly by somatization symptoms of psychological distress, suggesting extra efforts to provide more individualized epidemic information. Longitudinal research is required to further explore casual inferences.

Forest colors are important elements for public enjoying the scenery. So increasing attention has been acquired on forest color cognition. However researches on relationship between forest colors and public response are still insufficient, which cannot provide sufficient theoretical basis for the regulation of forest landscape in color. Therefore, We seek to examine the relationship between forest color and visual behavior based on eye tracking technology, and further interpret the visual indicators through the value of scenic beauty. This study researched Jiaozi Mountain in China by selecting 29 sampling points, counting up 116 photographs in 4 seasons by a mountainous region. On this basis, Matlab was performed to quantitatively extract color elements, while ArcGIS and Fragstats were applied to extract the spatial index of color patches. A total of 10 indicators were obtained to explain the color characteristics of each forest image. Through both visual behavior experiment and landscape preference evaluation, the results showed that people tend to have different visual behaviors and preference cognition when observing forest colors of different seasonal types. Based on the study of forest landscape color in all seasons, the subjects tend to judge the image in comparison to other seasonal forest landscape color photos to identify it more easily. For a single-season forest colors, diversified color information and abundant visual attention are important factors influencing the correlation between visual behavior, landscape preference, and forest color characteristics. This study aims to further reveal people's perceptions and psychological preference to forest colors, contribute to the establishment of a more quantitative and scientific scenery evaluation system, and provide a scientific basis for forest color planning and design.

Paratuberculosis a contagious and chronic disease in domestic and wild ruminants, is caused by Mycobacterium avium subspecies paratuberculosis (MAP). Typical clinical signs include intractable diarrhea, progressive emaciation, proliferative enteropathy, and mesenteric lymphadenitis. Paratuberculosis is endemic to many parts of the world and responsible for considerable economic losses. In this study, different types of paratuberculosis and MAP in sheep and goats were investigated in Inner Mongolia, a northern province in China contiguous with two countries and eight other provinces. A total of 4434 serum samples were collected from six cities in the western, central, and eastern regions of Inner Mongolia and analyzed using the ELISA test. In addition, tissue samples were collected from seven animals that were suspected to be infected with MAP. Finally, these tissues samples were analyzed by histopathological examination followed by polymerase chain reaction (PCR), IS1311 PCR-restriction enzyme analysis (PCR-REA), and a sequence analysis of five genes. Among all 4434 ruminant serum samples collected from the six cities in the western, central, and eastern regions of Inner Mongolia, 7.60% (337/4434) measured positive for the MAP antibody. The proportions of positive MAP antibody results for serum samples collected in the western, central, and eastern regions were 5.10% (105/2058), 6.63% (85/1282), and 13.44% (147/1094), respectively. For the seven suspected infected animals selected from the herd with the highest rate of positivity, the gross pathology and histopathology of the necropsied animals were found to be consistent with the pathological features of paratuberculosis. The PCR analysis further confirmed the diagnosis of paratuberculosis. The rest of the results demonstrated that herds of sheep and goats in Inner Mongolia were infected with both MAP type II and type III. To the best of our knowledge, this is the first study of the two subtypes of MAP strains in sheep and goats in Inner Mongolia.

IntroductionE-cigarette advertising has been shown to increase e-cigarette awareness and use. Although e-cigarette marketing in the early 2010s has been well-documented, little is known about how it has changed in recent years in response to the regulatory scrutiny from the FDA and the Congress to combat youth vaping epidemic. This study aims to examine the exposure to e-cigarette TV advertising among youth and adults in the U.S. from 2013 to 2019, overall and by media market and brand.MethodsQuarterly data on e-cigarette TV advertising exposure, measured by target rating points (TRPs), and expenditures from 2013 to 2019 were compiled from the StradegyTM of Kantar Media. Trends of quarterly e-cigarette advertising TRPs were reported by age group, market, and brand.ResultsOver the study period, overall exposure to e-cigarette TV advertising was higher among adults than among youth. E-cigarette advertising TRPs and expenditures were relatively stable, despite intermittent fluctuations, between 2013 Q1 and 2017 Q1 except for a one-time dip in 2015 Q3, followed by a sharp decline in 2017 Q2 and stayed low till the end of 2018. A resurgence of e-cigarette advertising TRPs occurred in 2019 Q1, led by the advertising from JUUL, Blu, and Vuse, which peaked in the third quarter of 2019, with quarterly TRPs reaching 316.8 for youth and 1,701.9 for adults, and quarterly advertising expenditure totaling $31 million.ConclusionsSignificant variations, both over time and across media markets and brands, were observed for e-cigarette televised advertising between 2013 and 2019. Following a lull in TV advertising in 2017/18, major e-cigarette companies have substantially increased advertising of their products on American television since early 2019, resulting in a surge in exposure to e-cigarette advertising among both youth and adults. Our findings highlighted the importance of continued monitoring of e-cigarette advertising in the U.S.

The small (18S) and large (28S) nuclear ribosomal DNA (rDNA) introns have been researched and sequenced in a variety of ectomycorrhizal fungal taxa in this study, it is found that both 18S and 28S rDNA would contain introns and display some degree variation in size, nucleotide sequences and insertion positions within the same fungi species (Meliniomyces). Under investigations among the tested isolates, 18S rDNA has four sites for intron insertions, 28S rDNA has two sites for intron insertions. Both 18S and 28S rDNA introns among the tested isolates belong to group I introns with a set of secondary structure elements designated P1-P10 helics and loops. We found a 12 nt nucleotide sequences TACCACAGGGAT at site 2 in the 3'-end of 28S rDNA, site 2 introns just insert the upstream or the downstream of the12 nt nucleotide sequences. Afters sequence analysis of all 18S and 28S rDNA introns from tested isolates, three high conserved regions around 30 nt nucleotides (conserved 1, conserved 2, conserved 3) and identical nucleotides can be found. Conserved 1, conserved 2 and conserved 3 regions have high GC content, GC percentage is almost more than 60%. From our results, it seems that the more convenient host sites, intron sequences and secondary structures, or isolates for 18S and 28S rDNA intron insertion and deletion, the more popular they are. No matter 18S rDNA introns or 18S rDNA introns among tested isolates, complementary base pairing at the splicing sites in P1-IGS-P10 tertiary helix around 5'-end introns and exons were weak.

BackgroundThe population in Jiamusi has been reported to have the highest prevalence of colorectal cancer (CRC) in China. The genetic causal-effect for this occurrence among the residents remains unclear. Given the long cold seasons with people wearing more clothes and reduced UV exposure, we aimed to study the association between the vitamin D metabolism-related gene CYP24A1 polymorphism and CRC susceptibility.MethodA case-control study was conducted that included 168 patients with CRC and 710 age-matched healthy individuals as the control group. Plausible susceptible variations were sought and clinical phenotypic-genotype association analysis was performed.ResultsOverall, two CYP24A1 polymorphisms, rs6013905 AX (P = 0.02, OR = 1.89, 95%CI: 1.09-3.29) and rs2762939 GX (P = 0.02, OR = 1.52, 95%CI: 1.08-2.13) were significantly associated with CRC in the Jiamusi population. In the female group, three CYP24A1 polymorphisms, rs6013905 AX (P = 0.04, OR = 2.59, 95%CI: 1.03-6.49), rs2762939 GX (P = 0.01, OR = 2.35, 95%CI: 1.25-4.42), and rs6068816 GG (P = 0.05, OR = 1.89, 95%CI: 0.99-3.59) carriers were significantly associated with CRC. In clinical phenotypic-genotype analysis, rs6013905 GG (P = 0.05, OR = 4.00, 95%CI: 0.92-17.48) and rs2762939 GX (P = 0.03, OR = 4.87, 95%CI: 1.00-23.69) carriers were significantly associated with poorly differentiated CRC, while CYP24A1 rs6068816 AX was significantly associated with the tumor type (P = 0.02, OR = 2.08, 95%CI: 1.10-3.96) and location (P = 0.04, OR = 2.24, 95%CI: 1.05-4.77).ConclusionCYP24A1 gene polymorphism may be a genetic risk factor attributable to the highest prevalence of CRC in Jiamusi people. Individuals with CYP24A1 gene polymorphism may have an increased barrier for vitamin D absorption, thus contributing to the risk of CRC development.

Lonicera macranthoides Hand.-Mazz (L. macranthoides) is a medicinal herb that is widely distributed in South China. The developmental stage and corolla dehiscence of the flower are the important factors affecting the quality of medicinal ingredients. However, neither the regulatory mechanism controlling chlorogenic acids biosynthesis in L. macranthoides nor the molecular basis of effect of corolla dehiscence on the quality of medicinal materials is fully understood. In this study, metabolomics and transcriptomics were used to analyze the metabolic and transcriptional differences of two different cultivars closed bud type (Bt), and flowering type (Ft), as well as the effect of jasmonic acid methyl ester (MeJA) on chlorogenic acids (CGAs) biosynthesis. In total, large number of differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs) were filtered among three lines of samples. Gene metabolite correlation analyses revealed a 'core set' of 30 genes and 54 genes that were strongly correlated with CGAs biosynthesis and regulating the flowering, respectively. Quantitative real-time polymerase chain reaction results proved the alterations in the expression levels of genes encoding the pathways involved in CGAs biosynthesis. The ion abundances of CGAs were most significantly increased, while some of the CGAs derived and Caffeoyl-CoA-derived substances showed the most largely reduced abundances in the closed bud type (Bt) compared to the flowering type (Ft). MeJA may leads to the activation of downstream genes in CGAs biosynthesis pathway. Overall, there were significant differences in the transcriptional and metabolic levels of CGAs biosynthesis pathway in flower buds of different flowering cultivars. The redirection of metabolic flux may contribute to increased accumulation of CGAs. However, whether MeJA and flowering have direct effects on the accumulation of CGAs needs further studied. These researches effectively expanded the functional genomic library and provide new insights into CGAs biosynthesis in L. macranthoides.

Autophagy is a conserved cellular process playing a role in maintenance of cellular homeostasis and response to changing nutrient conditions via degradation and recirculation of cellular redundant components. Autophagy-related proteins (Atg) play important function in autophagy pathway. Aedes albopictus mosquito is an effective vector transmitting multiple viruses which cause serious human diseases. Moreover, Aedes albopictus mosquito is becoming a serious threat to human health due to its widening distribution in recent years and thus worth of more research attention. It was reported that autophagy might play a role in viral infection in Aedes mosquito. To better understand the interaction between autophagy and arbovirus infection in mosquito system, it is necessary to identify autophagy pathway in the system. However, autophagy in Aedes albopictus mosquito is still poorly understood so far. We recently identified AaAtg8, the first Atg protein reported in Aedes albopictus mosquito. This work further identified twelve atg genes in Aedes albopictus mosquito. Sequence and phylogenetic analysis of the twelve atg genes were performed. Expression profiles of all the twelve Aaatg genes in different developmental stages and genders of Aedes albopictus mosquito were conducted. Effects of chemicals inhibiting or inducing autophagy on the levels of eight identified AaAtg proteins were examined. The function of two identified AaAtg proteins AaAtg6 and AaAtg16 and their response to arbovirus SINV infection were studied preliminarily. Taken together, this work systematically identified Aedes albopictus atg genes and provided basic information which might help to elucidate the autophagy pathway and the role of autophagy in arbovirus infection in Aedes mosquito system.

Reopening amid the COVID-19 pandemic has triggered a battle on social media. The supporters perceived that the lockdown policy could damage the economy and exacerbate social inequality. By contrast, the opponents believed it was necessary to contain the spread and ensure a safe environment for recovery. Anatomy into the battle is of importance to address public concerns, beliefs, and values, thereby enabling policymakers to determine the appropriate solutions to implement reopening policy. To this end, we investigated over 1.5 million related Twitter postings from April 17 to May 30, 2020. With the aid of natural language processing (NLP) techniques and machine learning classifiers, we classified each tweet into either a "supporting" or "opposing" class and then investigated the public perception from temporal and spatial perspectives. From the temporal dimension, we found that both political and scientific news that were extensively discussed on Twitter led to the perception of opposing reopening. Further, being the first mover with full reopen adversely affected the public reaction to reopening policy, while being the follower or late mover resulted in positive responses. From the spatial dimension, the correlation and regression analyses suggest that the state-level perception was very likely to be associated with political affiliation and health value.

Gardenia jasminoides Ellis (G. jasminoides) fruits are used as a resource for obtaining natural colorants and in traditional Chinese herbal medicine. However, G. jasminoides presents a relatively long flowering period and different ripening periods, so there are significant differences in the accumulation of metabolites in fruits of different colors. In addition, the complete metabolic pathways of iridoidsand crocins, which are used as medicinal composition of G. jasminoides, are poorly understood at present. In this research, we comprehensively compared the transcriptome and metabolites profiles of the developmental stages and locations of iridoid and crocin biosynthesis. A large number of differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs) were detected in four groups of samples, and clear variation in the pattern of metabolite abundance and gene expression were observed among different fruit colors and parts. Geniposide and gardenoside mainly accumulated in the sarcocarp of green fruit (GFS) and the sarcocarp of red fruit (FS), respectively. Crocin mainly accumulated in the peel and sarcocarp of red fruits. In the iridoid pathway, we hypothesized that there was a transport mechanism from the sarcocarp to the peel of G. jasminoides because of the inconsistent expression of G8O, 10-HGO and IS associated with differences in fruit ripening. UGTs play an important role in the biosynthesis of the active components of G. jasminoides. Combined transcriptome and metabonomics analysis showed a negative correlation between the biosynthesis of geniposide and crocin. The redirection of the metabolic flux and the regulation of key enzymes may be the main reasons for the changes in the biosynthesis of iridoid and crocin in G. jasminoides fruit. Our study expended valuable information for functional genomic library and provided new insights for metabolic engineering of secondary metabolite in G. Jasminoides.

BackgroundEthyl ferulate (EF) is a derivative of ferulic acid (FA), which is a monomeric component purified from the traditional medicinal herb Ferula, but its effects have not been clear yet. The purpose of this study was to evaluate whether EF can reduce inflammation levels in macrophages by regulating the Nrf2-HO-1 and NF-кB pathway.MethodsThe LPS-induced raw 264.7 macrophage cells model was used to determine the anti-inflammatory and anti-oxidative stress effects of EF. The levels of IL-1β, IL-6, TNF-α and PGE2 were analyzed by ELISA. The mRNA and protein of COX-2, iNOS, TNF-α, IL-6, HO-1 and Nrf2 were identified by RT-PCR analysis and western blotting. Intracellular ROS levels were assessed with DCFH oxidation staining. The expressions of NF-кB p-p65 and Nrf2 were analyzed by immunofluorescence assay. The inhibitory effect of Nrf2 inhibitor ML385 (2μM) on mediatation of antioxidant activity by raw 264.7 macrophage cells was evaluated. The effect of EF was confirmed in acute lung injury mice model.ResultsIn our research, EF reduced the expression of iNOS, COX2 and the production of PGE2. EF could inhibit the production of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) in lipopolysaccharide (LPS) stimulated macrophages and decreased expression of IL-6 and TNF-α in LPS stimulated macrophages. Furthermore, EF inhibited NF-кB p65 from transporting to the nucleus, decreased the expression of p-IкBα, significantly decreased the level of intracellular reactive oxygen species (ROS) and activated Nrf2/HO-1 pathways. EF could attenuate the degree of leukocyte infiltration, reduced MPO activity, mRNA levels and secretion of TNF-α and IL-6 in vivo. EF exhibited potent protective effects against LPS-induced acute lung injury in mice.ConclusionsCollectively, our data showed that EF relieved LPS-induced inflammatory responses by inhibiting NF-κB pathway and activating Nrf2/HO-1 pathway, known to be involved in the regulation of inflammatory responses by Nrf2.

Fangcang shelter hospitals were established in China during the coronavirus disease 2019 (COVID-19) pandemic as a countermeasure to stop the spread of the disease. To our knowledge, no research has been conducted on mental health problems among patients in Fangcang shelter hospitals. This study aimed to determine the prevalence and major influencing factors of anxiety and depressive symptoms among COVID-19 patients admitted to Fangcang shelter hospitals. From February 23, 2020, to February 26, 2020, we obtained sociodemographic and clinical characteristics information of COVID-19 patients in Jianghan Fangcang Shelter Hospital (Wuhan, China) and assessed their mental health status and sleep quality. Data were obtained with an online questionnaire. The questionnaire consisted of a set of items on demographic characteristics, a set of items on clinical characteristics, the Self-Rating Anxiety Scale, Self-Rating Depression Scale, and Pittsburgh Sleep Quality Index. Three hundred seven COVID-19 patients who were admitted to Jianghan Fangcang Shelter Hospital participated in this study. The prevalence of anxiety and depressive symptoms were 18.6% and 13.4%, respectively. Poor sleep quality and having ≥ two current physical symptoms were independent risk factors for anxiety symptoms. Female sex, having a family member with confirmed COVID-19, and having ≥ two current physical symptoms were independent risk factors for depressive symptoms. Anxiety and depressive symptoms were found to be common among COVID-19 patients in Fangcang Shelter Hospital, with some patients being at high risk.

This study aimed to investigate the associations of physical activity (PA) and screen time (ST) with physiological, psychological, and social health-particularly regarding effects on sleep quality-among Chinese college freshmen. A cross-sectional survey was conducted at Renmin University of China, in Beijing. A total of 5,233 students were surveyed in September 2015. Participants completed a self-report questionnaire on their demographic characteristics, tobacco and alcohol use, PA, ST, sleep quality, and health status. Multivariate logistic regression was performed to examine the independent and interactive associations between PA and ST with sleep quality and suboptimal health status. In total, 10.43%, 13.18%, and 13.26% of the 5,233 students had physiological, psychological, and social suboptimal health status, respectively. The prevalence of poor sleep quality was 37.94%. High ST and high PA were significantly associated with physiological suboptimal health status (aOR = 1.39, 95% CI: 1.16-1.68, and aOR = 0.55, 95% CI: 0.45-0.71), psychological suboptimal health status (aOR = 1.43, 95% CI: 1.21-1.69, and aOR = 0.57, 95% CI: 0.47-0.69), social suboptimal health status (aOR = 1.27, 95% CI: 1.08-1.50, and aOR = 0.63, 95% CI: 0.52-0.77), and poor sleep quality (aOR = 1.20, 95% CI: 1.03-1.39, and aOR = 0.64, 95% CI: 0.55-0.76). Additionally, low ST and high PA were interactively negatively associated with poor sleep quality (aOR = 0.56, 95% CI: 0.45-0.70), physiological suboptimal health status (aOR = 0.49, 95% CI: 0.40-0.59), psychological suboptimal health status (aOR = 0.48, 95% CI: 0.39-0.58), and social suboptimal health status (aOR = 0.49, 95% CI: 0.40-0.59). These findings suggested there are independent and interactive associations of low ST and high PA with poor sleep quality and suboptimal health status among Chinese college freshmen.

Citrus Huanglongbing (HLB), which is also known as citrus greening, is a destructive disease continuing to devastate citrus production worldwide. Although all citrus varieties can be infected with 'Candidatus Liberibacter asiaticus' (CaLas), a certain level of HLB tolerance of scion varieties can be conferred by some rootstocks. To understand the effects of rootstock varieties on orange fruit under CaLas stress, comparative iTRAQ proteomic profilings were conducted, using fruit from 'Valencia' sweet orange grafted on the sensitive ('Swingle') and tolerant rootstocks (a new selection called '46x20-04-48') infected by CaLas as experimental groups, and the same plant materials without CaLas infection as controls. The symptomatic fruit on 'Swingle' had 573 differentially-expressed (DE) proteins in comparison with their healthy fruit on the same rootstock, whereas the symptomatic fruit on '46x20-04-48' had 263 DE proteins. Many defense-associated proteins were down-regulated in the symptomatic fruit on 'Swingle' rootstock that were seldom detected in the symptomatic fruit on the '46x20-04-48' rootstock, especially the proteins involved in the jasmonate biosynthesis (AOC4), jasmonate signaling (ASK2, RUB1, SKP1, HSP70T-2, and HSP90.1), protein hydrolysis (RPN8A and RPT2a), and vesicle trafficking (SNAREs and Clathrin) pathways. Therefore, we predict that the down-regulated proteins involved in the jasmonate signaling pathway and vesicle trafficking are likely to be related to citrus sensitivity to the CaLas pathogen.

ObjectiveMature hair follicles represent an important stage of hair follicle development, which determines the stability of hair follicle structure and its ability to enter the hair cycle. Here, we used weighted gene co-expression network analysis (WGCNA) to identify hub genes of mature skin and hair follicles in Inner Mongolian cashmere goats.MethodsWe used transcriptome sequencing data for the skin of Inner Mongolian cashmere goats from fetal days 45-135 days, and divided the co expressed genes into different modules by WGCNA. Characteristic values were used to screen out modules that were highly expressed in mature skin follicles. Module hub genes were then selected based on the correlation coefficients between the gene and module eigenvalue, gene connectivity, and Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The results were confirmed by quantitative polymerase chain reaction (qPCR).ResultsTen modules were successfully defined, of which one, with a total of 3166 genes, was selected as a specific module through sample and gene expression pattern analyses. A total of 584 candidate hub genes in the module were screened by the correlation coefficients between the genes and module eigenvalue and gene connectivity. Finally, GO/KEGG functional enrichment analyses detected WNT10A as a key gene in the development and maturation of skin hair follicles in fetal Inner Mongolian cashmere goats. qPCR showed that the expression trends of 13 genes from seven fetal skin samples were consistent with the sequencing results, indicating that the sequencing results were reliable.n.

Houttuynia cordata (Saururaceae), an ancient and relic species, has been used as an important medicinal and edible plant in most parts of Asia. However, because of the lack of genome information and reliable molecular markers, studies on its population structure, or phylogenetic relationships with other related species are still rare. Here, we de novo assembled the complete chloroplast (cp) genome of H. cordata using the integration of the long PacBio and short Illumina reads. The cp genome of H. cordata showed a typical quadripartite cycle of 160,226 bp. This included a pair of inverted repeats (IRa and IRb) of 26,853 bp, separated by a large single-copy (LSC) region of 88,180 bp and a small single-copy (SSC) region of 18,340 bp. A total of 112 unique genes, including 79 protein-coding genes, 29 tRNA genes, and four rRNA genes, were identified in this cp genome. Eighty-one genes were located on the LSC region, 13 genes were located on the SSC region, and 17 two-copy genes were located on the IR region. Additionally, 48 repeat sequences and 86 SSR loci, which can be used as genomic markers for population structure analysis, were also detected. Phylogenetic analysis using 21 cp genomes of the Piperales family demonstrated that H. cordata had a close relationship with the species within the Aristolochia genus. Moreover, the results of mVISTA analysis and comparisons of IR regions demonstrated that the cp genome of H. cordata was conserved with that of the Aristolochia species. Our results provide valuable information for analyzing the genetic diversity and population structure of H. cordata, which can contribute to further its genetic improvement and breeding.

The identification of anammox bacteria is mostly relied on PCR with various marker genes. However, the community composition revealed by different marker genes and whether the marker genes influence the resulted community composition remain unclear. We compared the community structure of anammox bacteria in enriched and natural environments revealed by 16S rRNA and functional genes (hzo, hzsA and hzsB) from public database and published papers. The genus of Ca. Scalindua showed the lowest similarities with other genera, especially for the hzsA gene (66.9%-68.6%). The 16S rRNA gene is the most commonly used marker gene in natural habitats with 151 out 221 papers in total. The anammox bacterial community composition is distributed according to the source of habitat regardless the use of various marker genes. The role of marker gene is limited with explanatory of 5.4% for variance of community composition, versus 20.5% of habitat. The effect of marker gene is mainly acted on freshwater habitat, which shows significant different community composition revealed by 16S rRNA and hzo, with Ca. Brocadia and Ca. Jettenia as dominant genus, respectively.

Systematic interrogation of tumor-infiltrating immune cells (TIICs) is key to the prediction of clinical outcome and development of immunotherapies. However, little is known about the TIICs of hepatocellular carcinoma (HCC) and its impact on the prognosis of patients and potential for immunotherapy. We applied CIBERSORT of 1090 tumors to infer the infiltration of 22 subsets of TIICs using gene expression data. Unsupervised clustering analysis by 22 TIICs revealed 4 clusters of tumors, mainly defined by macrophages and T cells, with distinct prognosis and associations with immune checkpoint molecules, including PD-1, CD274, CTLA-4, LAG-3 and IFNG. We found tumors with decreased number of M1 macrophages or increased regulatory T cells were associated with poor prognosis. Based on the multivariate Cox analysis, a nomogram was also established for clinical application. In conclusion, composition of the TIICs in HCC was quite different, which is an important determinant of prognosis with great potential to identify candidates for immunotherapy.

The objective of this study was to elucidate the burden, risk factors, and prognosis of serious non-AIDS-defining events among admitted cART-naive AIDS patients in China. The evaluation of the burden, risk factors and prognosis of serious NADEs was carried out among 1309 cART-naive AIDS patients (median age: 38.2 years, range: 18-78 years) admitted in Beijing Ditan Hospital between January 2009 and December 2018. Among 1309 patients, 143 patients (10.9%) had at least one serious NADEs, including 49 (3.8%) with cerebrovascular diseases, 37 (2.8%) with non-AIDS-defining cancers, 28 (2.1%) with chronic kidney diseases, 26 (2.0%) with cardiovascular diseases, and 18 (1.4%) with liver cirrhosis. Serious NADEs distributed in different age and CD4 levels, especially with age ≥50 years and CD4 ≤350 cells/ul. Other traditional risk factors, including cigarette smoking (OR = 1.9, 95%CI = 1.3-2.8, p = 0.002), hypertension (OR = 2.5, 95%CI = 1.7-3.7, p

Hepatitis C virus (HCV) replication involves many viral and host factors. Host factor SPRY domain- and SOCS box-containing protein 2(SPSB2) belongs to SPSB family, and it recruits target proteins by the SPRY domain and forms E3 ubiquitin ligase complexes by the SOCS box. As an adaptor protein, it can regulate the host's response to infection, but little is known about whether SPSB2 plays a role in HCV replication. In the present study, we found that HCV infection significantly upregulated the mRNA and protein levels of SPSB2 in HCVcc-infected cells. Exogenous expression of SPSB2 in hepatoma cells decreased HCV RNA and protein levels which depended on the SOCS box, while knockdown of endogenous SPSB2 increased HCV RNA and protein levels. Additionally, we demonstrated that SPSB2 interacted with HCV structural protein E1 and nonstructural protein protein 5A (NS5A) via the C-terminal portion of the SPSB2 SPRY domain. Furthermore, SPSB2 induced NS5A ubiquitination and mediated NS5A degradation. Collectively, this study discovered host factor SPSB2 significantly inhibits HCV replication by interacting and degrading NS5A.

MiRNAs and proteins play important roles in different stages of breast tumor development and serve as biomarkers for the early diagnosis of breast cancer. A new algorithm that combines machine learning algorithms and multilayer complex network analysis is hereby proposed to explore the potential diagnostic values of miRNAs and proteins. XGBoost and random forest algorithms were employed to screen the most important miRNAs and proteins. Maximal information coefficient was applied to assess intralayer and interlayer connection. A multilayer complex network was constructed to identify miRNAs and proteins that could serve as biomarkers for breast cancer. Proteins and miRNAs that are nodes in the network were subsequently categorized into two network layers considering their distinct functions. The betweenness centrality was used as the first measurement of the importance of the nodes within each single layer. The degree of the nodes was chosen as the second measurement to map their signalling pathways. By combining these two measurements into one score and comparing the difference of the same candidate between normal tissue and cancer tissue, this novel multilayer network analysis could be applied to successfully identify molecules associated with breast cancer.

Tight junction barrier is critical to intestinal homeostasis. Applying antibiotics to treat infections is common in clinical practice, which may affect intestinal microbiota. Intestinal microbiota dysbiosis is involved in the occurrence of some gastrointestinal diseases. Therefore, this study was aimed to investigate the influence of antibiotics on intestinal tight junction barrier and the possible underlying mechanisms. Healthy adult female C57BL/6 mice were treated with a broad-spectrum antibiotic cocktail for 14 days. 16S rDNA Illumina sequencing and headspace gas chromatography-mass spectrometry (HS-GC/MS) were respectively used to analyze microbial community and to detect short-chain fatty acids (SCFAs) contents. In vivo intestinal paracellular permeability to fluorescein isothiocyanate-dextran (FITC-dextran) was measured. Protein expression was determined by immunoblotting. Immunofluoresence was applied to observe the distributions of ZO-1, LC3B and ASC. Antibiotics remarkably altered intestinal microbiota composition in healthy mice, accompanying reduced SCFAs' concentrations. In addition, the intestinal tight junction barrier was disrupted by antibiotic treatment, as evidenced by increased intestinal paracellular permeability to FITC-dextran, decreased tight junction protein expressions, and disrupted ZO-1 morphology. Furthermore, NLRP3 inflammasome and autophagy were activated by antibiotic treatment. In conclusion, intestinal epithelial tight junction barrier dysfunction induced by antibiotics is associated with intestinal microbiota dysbiosis, activated NLRP3 inflammasome and autophagy in mice.

Cyclocarya paliurus is a unique tree species of that grows in southern China. The tree contains distinctive saponins in the leaf that has hypoglycemic and hypolipidemic effects. It was aimed to detect localization of saponins and suitable time of harvest for medicinal uses. Histochemical, cytochemical localization and UV-spectrophotometry were carried out in C. paliurus plant. We found that in all organs, the saponins were primarily located in the parenchyma cells and the highest saponins accumulation was in the palisade tissue in leaves. Cytochemical localization results indicated that saponins were mainly distributed in the chloroplast, vesicle, and plasmalemma. On average, the total saponins content in leaves (20.57 mg·g-1) was two and three times greater than in root (10.19 mg·g-1) and shoot (6.20 mg·g-1), respectively. Moreover, the saponins content in the leaf and root exhibited fluctuations, which were highest in September. Considering saponins levels and biomass, we conclude that harvesting all leaves in September is an economical and effective strategy for medicinal use in C. paliurus.

[This corrects the article DOI: 10.1371/journal.pone.0099067.].

[This corrects the article DOI: 10.1371/journal.pone.0164646.].

Male mammals must simultaneously produce prodigious numbers of sperm and maintain an adequate reserve of stem cells to ensure continuous production of gametes throughout life. Failures in the mechanisms responsible for balancing germ cell differentiation and spermatogonial stem cell (SSC) self-renewal can result in infertility. We discovered a novel requirement for Ubiquitous Expressed Transcript (UXT) in spermatogenesis by developing the first knockout mouse model for this gene. Constitutive deletion of Uxt is embryonic lethal, while conditional knockout in the male germline results in a Sertoli cell-only phenotype during the first wave of spermatogenesis that does not recover in the adult. This phenotype begins to manifest between 6 and 7 days post-partum, just before meiotic entry. Gene expression analysis revealed that Uxt deletion downregulates the transcription of genes governing SSC self-renewal, differentiation, and meiosis, consistent with its previously defined role as a transcriptional co-factor. Our study has revealed the first in vivo function for UXT in the mammalian germline as a regulator of distinct transcriptional programs in SSCs and differentiating spermatogonia.