Search

Abstract Background This paper investigated the link between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and diabetic kidney disease (DKD) in adult diabetic patients and identified the optimal NHHR value for impacting DKD. Methods This cross-sectional research made use of records from the National Health and Nutrition Examination Survey (NHANES) executed between 2005 and 2016. The link of NHHR to DKD risk was analyzed by logistic regression and restricted cubic spline (RCS) models. The stability and reliability of the results were assessed by subgroup analysis and sensitivity analysis. Results In total, 4,177 participants were involved. As a continuous variable, NHHR was markedly connected to an increased risk of DKD (OR 1.07, 95% CI 1.02, 1.12, P

Abstract Background Accurate prediction of subject recruitment, which is critical to the success of a study, remains an ongoing challenge. Previous prediction models often rely on parametric assumptions which are not always met or may be difficult to implement. We aim to develop a novel method that is less sensitive to model assumptions and relatively easy to implement. Methods We create a weighted resampling-based approach to predict enrollment in year two based on recruitment data from year one of the completed GRIPS and PACE clinical trials. Different weight functions accounted for a range of potential enrollment trajectory patterns. Prediction accuracy was measured by Euclidean distance for enrollment sequence in year two, total enrollment over time, and total weeks to enroll a fixed number of subjects, against the actual year two enrollment data. We compare the performance of the proposed method with an existing Bayesian method. Results Weighted resampling using GRIPS data resulted in closer prediction evidenced by better coverage of observed enrollment with the prediction intervals and smaller Euclidean distance from actual enrollment in year 2, especially when enrollment gaps were filled prior to the weighted resampling. These scenarios also produced more accurate predictions for total enrollment and number of weeks to enroll 50 participants. These same scenarios outperformed an existing Bayesian method for all 3 accuracy measures. In PACE data, using a reduced year 1 enrollment resulted in closer prediction evidenced by better coverage of observed enrollment with the prediction intervals and smaller Euclidean distance from actual enrollment in year 2, with the weighted resampling scenarios better reflecting the seasonal variation seen in year (1) The reduced enrollment scenarios resulted in closer prediction for total enrollment over 6 and 12 months into year (2) These same scenarios also outperformed an existing Bayesian method for relevant accuracy measures. Conclusion The results demonstrate the feasibility and flexibility for a resampling-based, non-parametric approach for prediction of clinical trial recruitment with limited early enrollment data. Application to a wider setting and long-term prediction accuracy require further investigation.

Abstract Background Bracts are important for ornamental plants, and their developmental regulation process is complex; however, relatively little research has been conducted on bracts. In this study, physiological, biochemical and morphological changes in Bougainvillea glabra leaves, leaf buds and bracts during seven developmental periods were systematically investigated. Moreover, transcriptomic data of B. glabra bracts were obtained using PacBio and Illumina sequencing technologies, and key genes regulating their development were screened. Results Scanning electron microscopy revealed that the bracts develop via a process involving regression of hairs and a color change from green to white. Transcriptome sequencing revealed 79,130,973 bp of transcript sequences and 45,788 transcripts. Differential gene expression analysis revealed 50 expression patterns across seven developmental periods, with significant variability in transcription factors such as BgAP1, BgFULL, BgCMB1, BgSPL16, BgSPL8, BgDEFA, BgEIL1, and BgBH305. KEGG and GO analyses of growth and development showed the involvement of chlorophyll metabolism and hormone-related metabolic pathways. The chlorophyll metabolism genes included BgPORA, BgSGR, BgPPH, BgPAO and BgRCCR. The growth hormone and abscisic acid signaling pathways involved 44 and 23 homologous genes, and coexpression network analyses revealed that the screened genes BgAPRR5 and BgEXLA1 are involved in the regulation of bract development. Conclusions These findings improve the understanding of the molecular mechanism of plant bract development and provide important guidance for the molecular regulation and genetic improvement of the growth and development of ornamental plants, mainly ornamental bracts.

Abstract Background While cervical cancer incidence rates (IR) in the United States have dropped in the last 20 years, non‐cervical human papillomavirus (HPV) associated cancers increased. Many people in Texas (TX) live in medically underserved areas and have higher risk of developing HPV‐associated cancers. Since previous studies of these regions focused on cervical cancer, we included other HPV‐associated cancers in our analysis of IR in East TX and the TX‐Mexico Border compared to other TX regions. Methods Cancer data from 2006 to 2019 were obtained from the TX Cancer Registry. Cases of HPV‐associated cervical, vaginal, vulvar, penile, anal, and oropharyngeal cancers and corresponding patient‐level demographic data were included. We calculated IR per 100,000 and drew heat maps to visualize cancer IR by county. To control potential confounders, we added county‐level risk factors: rates for smoking, excessive drinking, obesity, STIs, primary care provider availability and dentist availability, from the County Health Rankings and Roadmaps program. We reported IRs by region and time and estimated unadjusted and adjusted risk ratio (RR) for association of each type of cancer and region. Lastly, we created adjusted models for each cancer by period to see time trends of regional differences. Results Risk of anal, cervical, and oropharyngeal cancer was lower at parts of the Border than in the rest of TX in the adjusted model. We also observed increasing anal and oropharyngeal cancer risk and decreasing cervical and vaginal cancer risk over time. Conclusion Patient sociodemographics, behavioral risk factors, and access to care may contribute to some observed differences in cancer IR across regions. This indicates that targeted prevention efforts towards these regions, especially in low socioeconomic status communities, may benefit future generations.

Summary: Dysregulated host immune responses contribute to disease severity and worsened prognosis in COVID-19 infection and the underlying mechanisms are not fully understood. In this study, we observed that IL-33, a damage-associated molecular pattern molecule, is significantly increased in COVID-19 patients and in SARS-CoV-2-infected mice. Using IL-33−/− mice, we demonstrated that IL-33 deficiency resulted in significant decreases in bodyweight loss, tissue viral burdens, and lung pathology. These improved outcomes in IL-33−/− mice also correlated with a reduction in innate immune cell infiltrates, i.e., neutrophils, macrophages, natural killer cells, and activated T cells in inflamed lungs. Lung RNA-seq results revealed that IL-33 signaling enhances activation of inflammatory pathways, including interferon signaling, pathogen phagocytosis, macrophage activation, and cytokine/chemokine signals. Overall, these findings demonstrate that the alarmin IL-33 plays a pathogenic role in SARS-CoV-2 infection and provides new insights that will inform the development of effective therapeutic strategies for COVID-19.

Salmonella enterica serovar Gallinarum (S. gallinarum) is an important host-specific pathogen that causes fowl typhoid, a severe systemic, septicemic, and fatal infection, in chickens. S. gallinarum causes high morbidity and mortality in chickens and poses a significant burden and economic losses to the poultry industry in many developing countries. However, the virulence factors and mechanisms of S. gallinarum-induced systemic infection in chickens remain poorly understood. In this study, we constructed a Salmonella pathogenicity island-14 (SPI-14) mutant strain (mSPI-14) of S. gallinarum and evaluated the pathogenicity of mSPI-14 in the chicken systemic infection model. The mSPI-14 exhibited the same level of bacterial growth and morphological characteristics but significantly reduced resistance to bile acids compared with the wild-type (WT) strain in vitro. The virulence of mSPI-14 was significantly attenuated in the chicken oral infection model in vivo. Chickens infected with WT showed typical clinical symptoms of fowl typhoid, with all birds succumbing to the infection within 6 to 9 days post-inoculation, and substantial increases in bacterial counts and significant pathological changes in the liver and spleen were observed. In contrast, all mSPI-14-infected chickens survived, the bacterial counts in the organs were significantly lower, and no significant pathological changes were observed in the liver and spleen. The expression of interleukin (IL)-1β, IL-12, CXCLi1, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ in the liver of mSPI-14-infected chickens were significantly lower than those in the WT-infected chickens. These results indicate that SPI-14 is a crucial virulence factor in systemic infection of chickens, and avirulent mSPI-14 could be used to develop a new attenuated live vaccine to prevent S. gallinarum infection in chickens.

Viral variant is one known risk factor associated with post-acute sequelae of COVID-19 (PASC), yet the pathogenesis is largely unknown. Here, we studied SARS-CoV-2 Delta variant-induced PASC in K18-hACE2 mice. The virus replicated productively, induced robust inflammatory responses in lung and brain tissues, and caused weight loss and mortality during the acute infection. Longitudinal behavior studies in surviving mice up to 4 months post-acute infection revealed persistent abnormalities in neuropsychiatric state and motor behaviors, while reflex and sensory functions recovered over time. In the brain, no detectable viral RNA and minimal residential immune cell activation was observed in the surviving mice post-acute infection. Transcriptome analysis revealed persistent activation of immune pathways, including humoral responses, complement, and phagocytosis, and gene expression levels associated with ataxia telangiectasia, impaired cognitive function and memory recall, and neuronal dysfunction and degeneration. Furthermore, surviving mice maintained potent systemic T helper 1 prone cellular immune responses and strong sera neutralizing antibodies against Delta and Omicron variants months post-acute infection. Overall, our findings suggest that infection in K18-hACE2 mice recapitulates the persistent clinical symptoms reported in long-COVID patients and provides new insights into the role of systemic and brain residential immune factors in PASC pathogenesis.

The high temperature generated by the DC pantograph-catenary arc of urban rail systems will aggravate the wear of the pantograph-catenary system. When the ablation intensifies, it will lead to disconnection accidents on the contact line. In this paper, through the establishment of a pantograph-catenary arc model and contact line arc ablation model, considering the flow of the molten pool, it is reported that the temperature distribution of the pantograph-catenary arc is axisymmetric. With the increase in the arcing time, the maximum temperature of the arc increases. The heat flux density of the arc injection contact line presents a Gaussian distribution and is positively correlated with the arcing time. The high-temperature area of the contact line and the distribution of the molten pool show an approximate arc shape. The velocity of the molten pool shows a symmetrical distribution about the center of the electrode. The area, depth, and radius of the molten pool of the contact line increase with an increase in the arcing time, and the radius of the molten pool is always greater than the depth of the molten pool. The work presented in this paper is helpful to further our understanding of the basic physical process of pantograph-catenary arc ablation of contact lines.

Salmonella enterica serovar Gallinarum biovar Gallinarum (SG) causes fowl typhoid, a notifiable infectious disease in poultry. However, the pathogenic mechanism of SG-induced systemic infection in chickens remains unclear. Thioredoxin reductase (TrxB) is a redox protein crucial for regulating various enzyme activities in Salmonella serovar, but the role in SG-induced chicken systemic infection has yet to be determined. Here, we constructed a mutant SG strain lacking the trxB gene (trxB::Cm) and used chicken embryo inoculation and chicken oral infection to investigate the role of trxB gene in the pathogenicity of SG. Our results showed that trxB::Cm exhibited no apparent differences in colony morphology and growth conditions but exhibited reduced tolerance to H2O2 and increased resistance to bile acids. In the chicken embryo inoculation model, there was no significant difference in the pathogenicity of trxB::Cm and wild-type (WT) strains. In the chicken oral infection, the WT-infected group exhibited typical clinical symptoms of fowl typhoid, with complete mortality between days 6 and 9 post infection. In contrast, the trxB::Cm group showed a 100% survival rate, with no apparent clinical symptoms or pathological changes observed. The viable bacterial counts in the liver and spleen of the trxB::Cm-infected group were significantly reduced, accompanied by decreased expression of cytokines and chemokines (IL-1β, IL-6, IL-12, CXCLi1, TNF-α, and IFN-γ), which were significantly lower than those in the WT group. These results show that the pathogenicity of the trxB-deficient strain was significantly attenuated, indicating that the trxB gene is a crucial virulence factor in SG-induced systemic infection in chickens, suggesting that trxB may become a potentially effective target for controlling and preventing SG infection in chickens.

Scrub typhus is a leading cause of febrile illness in endemic countries due to infection with Orientia tsutsugamushi (Ot), a seriously understudied intracellular bacterium. Pulmonary involvement associated with vascular parasitism in patients is common and can develop into life threatening interstitial pneumonia. The diverse antigenicity of Ot genotypes and inter-strain differences in genome content are connected to varied virulence and clinical outcomes; however, detailed studies of strain-related pulmonary immune responses in human patients or small animal models of infection are lacking. In this study, we have used two clinically prevalent bacterial strains (Karp and Gilliam) to reveal cellular immune responses in inflamed lungs and potential biomarkers of disease severity. The results demonstrate that outbred CD-1 mice are highly susceptible to both Karp and Gilliam strains; however, C57BL/6 (B6) mice were susceptible to Karp, but resistant to Gilliam (with self-limiting infection), corresponding to their tissue bacterial burdens and lung pathological changes. Multicolor flow cytometric analyses of perfused B6 mouse lungs revealed robust and sustained influx and activation of innate immune cells (macrophages, neutrophils, and NK cells), followed by CD4+ and CD8+ T cells, during Karp infection, but such responses were greatly attenuated during Gilliam infection. The robust cellular responses in Karp-infected B6 mice positively correlated with significantly early and high levels of serum cytokine/chemokine protein levels (CXCL1, CCL2/3/5, and G-CSF), as well as pulmonary gene expression (Cxcl1/2, Ccl2/3/4, and Ifng). In vitro infection of B6 mouse-derived primary macrophages also revealed bacterial strain-dependent immune gene expression profiles. This study provided the lines of evidence that highlighted differential tissue cellular responses against Karp vs. Gilliam infection, offering a framework for future investigation of Ot strain-related mechanisms of disease pathogenesis vs. infection control.

Summary: Monoclonal antibodies against the Ebola virus (EBOV) surface glycoprotein are effective treatments for EBOV disease. Antibodies targeting the EBOV glycoprotein (GP) head epitope have potent neutralization and Fc effector function activity and thus are of high interest as therapeutics and for vaccine design. Here we focus on the head-binding antibodies 1A2 and 1D5, which have been identified previously in a longitudinal study of survivors of EBOV infection. 1A2 and 1D5 have the same heavy- and light-chain germlines despite being isolated from different individuals and at different time points after recovery from infection. Cryoelectron microscopy analysis of each antibody in complex with the EBOV surface GP reveals key amino acid substitutions in 1A2 that contribute to greater affinity, improved neutralization potency, and enhanced breadth as well as two strategies for antibody evolution from a common site.

Abstract Background Loropetalum chinense var. rubrum (L. chinense var. rubrum) is a precious, coloured-leaf native ornamental plant in the Hunan Province. We found an L. chinense var. rubrum tree with three different leaf colours: GL (green leaf), ML (mosaic leaf), and PL (purple leaf). The mechanism of leaf coloration in this plant is still unclear. Therefore, this study aimed to identify the metabolites and genes involved in determining the colour composition of L. chinense var. rubrum leaves, using phenotypic/anatomic observations, pigment content detection, and comparative metabolomics and transcriptomics. Results We observed that the mesophyll cells in PL were purple, while those in GL were green and those in ML were a mix of purple-green. The contents of chlorophyll a, b, carotenoids, and total chlorophyll in PL and ML were significantly lower than those in GL. While the anthocyanin content in PL and ML was significantly higher than that in GL. The metabolomics results showed the differences in the content of cyanidin 3-O-glucoside, delphinidin 3-O-glucoside, cyanidin 3,5-O-diglucoside, pelargonidin, and petunidin 3,5-diglucoside in ML, GL, and PL were significant. Considering that the change trend of anthocyanin content change was consistent with the leaf colour difference, we speculated that these compounds might influence the colour of L. chinense var. rubrum leaves. Using transcriptomics, we finally identified nine differentially expressed structural genes (one ANR (ANR1217); four CYP75As (CYP75A1815, CYP75A2846, CYP75A2909, and CYP75A1716); four UFGTs (UFGT1876, UFGT1649, UFGT1839, and UFGT3273) and nine transcription factors (two MYBs (MYB1057 and MYB1211), one MADS-box (MADS1235), two AP2-likes (AP2-like1779 and AP2-like2234), one bZIP (bZIP3720), two WD40s (WD2173 and WD1867) and one bHLH (bHLH1631) that might be related to flavonoid biosynthesis and then impacted the appearance of colour in L. chinense var. rubrum leaves. Conclusion This study revealed potential molecular mechanisms associated with leaf coloration in L. chinense var. rubrum by analyzing differential metabolites and genes related to the anthocyanin biosynthesis pathway. It also provided a reference for research on leaf colour variation in other ornamental plants.

With the increasing speed of urban rail trains, the vibration between the pantograph collector strip and the contact wire intensifies, and the pantograph-catenary arc occurs frequently, which severely wear the surface materials of the pantograph-catenary. The arc burning strength and arc extinguishing characteristics of the pantograph-catenary arc are affected by the arc temperature parameters. Based on the theory of magnetohydrodynamics, this paper establishes a mathematical model with multi-physical field coupling. According to the mathematical model, apply COMSOL finite element software to establish a simulation model for the arc of the urban rail pantograph-catenary, and simulate and analyze the temperature field about the arc. Use an experimental platform to simulate experiments and verify the feasibility of the simulation model. Based on the simulation model, the surface temperature distribution of different collector strip materials under the action of urban rail pantograph-catenary arc is studied. The research results indicate that there is a positive connection between the arc duration of urban rail pantograph-catenary and the maximum arc temperature; Although the collector strip materials are different, the surface temperature distribution of the collector strip is the same; The surface temperature of the collector strip decreases with the increase of the thermal conductivity of the collector strip material.

Background Non-alcoholic fatty liver disease (NAFLD) has been increasing in association with the epidemic of obesity and diabetes. Peroxisomes are single membrane-enclosed organelles that play a role in the metabolism of lipid and reactive oxygen species. The present study examined the role of peroxisomes in high-fat diet (HFD)-induced NAFLD using fenofibrate, a peroxisome proliferator-activated receptor α (PPARα) agonist. Methods Eight-week-old male C57BL/6J mice were fed either a normal diet or HFD for 12 weeks, and fenofibrate (50 mg/kg/day) was orally administered along with the initiation of HFD. Results HFD-induced liver injury as measured by increased alanine aminotransferase, inflammation, oxidative stress, and lipid accumulation was effectively prevented by fenofibrate. Fenofibrate significantly increased the expression of peroxisomal genes and proteins involved in peroxisomal biogenesis and function. HFD-induced attenuation of peroxisomal fatty acid oxidation was also significantly restored by fenofibrate, demonstrating the functional significance of peroxisomal fatty acid oxidation. In Ppara deficient mice, fenofibrate failed to maintain peroxisomal biogenesis and function in HFD-induced liver injury. Conclusion The present data highlight the importance of PPARα-mediated peroxisomal fitness in the protective effect of fenofibrate against NAFLD.

Objective: To measure the association between housing insecurity and foregone medication due to cost among Medicare beneficiaries aged 65+ during the Recession. Methods: Data came from Medicare beneficiaries aged 65+ years from the 2006–2012 waves of the Health and Retirement Study (HRS). Two-wave housing insecurity changes are evaluated as follows: (i) No insecurity, (ii) Persistent insecurity, (iii) Onset insecurity, and (iv) Onset security. We implemented a series of four weighted longitudinal General Estimating Equation (GEE) models, two minimally adjusted and two fully adjusted models, to estimate the probability of foregone medications due to cost between 2008 and 2012. Results: Our study sample was restricted to non-proxy interviews of non-institutionalized Medicare beneficiaries aged 65+ in the 2006 wave (n = 9936) and their follow up visits (n = 8753; in 2008; n = 7464 in 2010; and n = 6594 in 2012). Results from our fully adjusted model indicated that the odds of foregone medication was 64% higher among individuals experiencing Onset insecurity versus No insecurity in 2008, and also generally larger for individuals experiencing Onset Insecurity versus Persistent Insecurity. Odds of foregone medication was also larger among females, minority versus non-Hispanic white adults, those reporting a chronic condition, those with higher medical expenditures, and those living in the South versus Northeast. Conclusion: This study drew from nationally representative data to elucidate the disparate health and financial impacts of a crisis on Medicare beneficiaries who, despite health insurance coverage, displayed variability in foregone medication patterns. Our findings suggest that the onset of housing insecurity is most closely linked with unexpected acute economic shocks leading households with little time to adapt and forcing trade-offs in their prescription and other needs purchases. Both housing and healthcare policy implications exist from these findings including expansion of low-income housing units and rent relief post-recession as well as wider prescription drug coverage for Medicare adults.

Background: Persons with HIV (PWH) have both more frequent depression and higher levels of plasma inflammatory biomarkers compared to persons without HIV (PWoH). Inflammation and depressive symptoms are linked, including in PWH; however, it is unclear whether these associations differ by HIV serostatus and biological sex. Methods: Six plasma inflammatory biomarkers were assessed using samples from PWH and PWoH who participated in six NIH-funded studies through the UCSD HIV Neurobehavioral Research Program (HNRP) from 2011 to 2019. Factor analysis was performed to identify intercorrelated groups of biomarkers. Factors and their components were then examined for relationships with Beck Depression Inventory-II (BDI-II) and modifying effects of sex or HIV serostatus using multivariable linear regression, adjusting for demographics, substance use diagnoses, and relevant co-morbidities. Results: Participants included 150 PWH (age = 48.3 ± 13.1 yr; 88% biologically male) and 138 PWoH (age = 46.3 ± 15.9; 56% male). Two inflammatory factors were identified: Factor 1 loaded on interleukin-6 (IL-6), C-reactive protein (CRP), and D-dimer; Factor 2 loaded on interleukin-8, chemokine C–C ligand 2 (CCL2), and chemokine C-X-C ligand 10 (CXCL10). Sex modified the effect of Factor 1 on BDI-II, with a more positive association for men than women (p = 0.04). No significant association between Factor 2 and BDI-II was found. Of the biomarkers in Factor 1, only IL-6 was significantly associated with BDI-II and was modified by sex (p = 0.003). In sex-stratified analysis, a positive association was found for men (β = 5.42; 95% confidence interval = [1.32, 9.52]) but not women (β = −3.88; 95% C.I. = [-11.02, 3.26]). No HIV-related interactions were detected. Interpretation: We identified a depression-associated inflammatory factor present in both PWH and PWoH, consistent with prior studies of PWH only. The association was driven by a correlation between IL-6 and depression exclusively in men, suggesting that the depression-inflammation link differs by sex. Future studies of depression etiology or treatment, including those on persons with HIV, should consider the impact of biological sex in both design and analysis.

Adversity stress is the main environmental factor limiting plant growth and development, including salt and other stress factors. This study delves into the adaptability and salt tolerance mechanisms of Machilus faberi Hemsl, a species with potential for cultivation in salinized areas. We subjected the plants to various salt concentrations to observe their growth responses and to assess key physiological and biochemical indicators. The results revealed that under high salt concentrations (500 and 700 mmol−1/L), symptoms such as leaf yellowing, wilting, and eventual death were observed. Notably, plant height and shoot growth ceased on the 14th day of exposure. Chlorophyll content (a, b, total a + b, and the a/b ratio) initially increased but subsequently decreased under varying levels of salt stress. Similarly, the net photosynthetic rate, stomatal conductance, leaf water content, and root activity significantly declined under these conditions. Moreover, we observed an increase in malondialdehyde levels and relative conductivity, indicative of cellular damage and stress. The activity of superoxide dismutase and ascorbate peroxidase initially increased and then diminished with prolonged stress, whereas peroxidase activity consistently increased. Levels of proline and soluble protein exhibited an upward trend, contrasting with the fluctuating pattern of soluble sugars, which decreased initially but increased subsequently. In conclusion, M. faberi exhibits a degree of tolerance to salt stress, albeit with growth limitations when concentrations exceed 300 mmol−1/L. These results shed light on the plant’s mechanisms of responding to salt stress and provide a theoretical foundation for its cultivation and application in salt-affected regions.

Site-specific N-, O-, and C-linked glycans are characterized in the ebolavirus envelope glycoprotein GP using mass spectrometry-based glycoproteomics.

Genes associated with increased susceptibility to multiple sclerosis (MS) have been identified, but their functions are incompletely understood. One of these genes codes for the RNA helicase DExD/H-Box Polypeptide 39B (DDX39B), which shows genetic and functional epistasis with interleukin-7 receptor-α gene (IL7R) in MS-risk. Based on evolutionary and functional arguments, we postulated that DDX39B enhances immune tolerance thereby decreasing MS risk. Consistent with such a role we show that DDX39B controls the expression of many MS susceptibility genes and important immune-related genes. Among these we identified Forkhead Box P3 (FOXP3), which codes for the master transcriptional factor in CD4+/CD25+ T regulatory cells. DDX39B knockdown led to loss of immune-regulatory and gain of immune-effector expression signatures. Splicing of FOXP3 introns, which belong to a previously unrecognized type of introns with C-rich polypyrimidine tracts, was exquisitely sensitive to DDX39B levels. Given the importance of FOXP3 in autoimmunity, this work cements DDX39B as an important guardian of immune tolerance.

Summary: Therapeutic antibodies are an important tool in the arsenal against coronavirus infection. However, most antibodies developed early in the pandemic have lost most or all efficacy against newly emergent strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), particularly those of the Omicron lineage. Here, we report the identification of a panel of vaccinee-derived antibodies that have broad-spectrum neutralization activity. Structural and biochemical characterization of the three broadest-spectrum antibodies reveal complementary footprints and differing requirements for avidity to overcome variant-associated mutations in their binding footprints. In the K18 mouse model of infection, these three antibodies exhibit protective efficacy against BA.1 and BA.2 infection. This study highlights the resilience and vulnerabilities of SARS-CoV-2 antibodies and provides road maps for further development of broad-spectrum therapeutics.

Abstract Background Breast cancer survivors have a unique risk for negative health outcomes. Engaging in routine physical activity (PA) can reduce these risks. However, PA levels are low among this population. Narrative visualization (NV) is a technique that uses drawings, photographs, and text to contextualize data, which may increase integrated regulation, or motivation related to personal values and identity. A PA intervention targeting breast cancer survivors using an NV strategy may improve PA behavior. The purpose of this study was to determine whether scrapbooking activities could successfully be used as an NV strategy for older (55+) breast cancer survivors. Methods Breast cancer survivors were given workbooks, wearable electronic activity monitors, instant cameras, and art supplies including a variety of stickers (e.g., emojis, affirmations). Participants were instructed to use these materials for 7 days. The workbook pages prompted participants to re-draw their daily activity graphs from the wearable’s mobile app, then annotate them with text, photographs, stickers, etc. to reflect what the data meant to them. Hybrid thematic analysis was used to analyze the photographs, drawings, and written content to identify emergent themes. Content analysis was also used to investigate use of stickers and photographs. Results Of the 20 consented women (mean age 67 ± 5 years, 45% non-Hispanic white), 3 participants were lost to follow-up or unable to complete the procedures. The NV procedures were successfully utilized by the remaining 17 participants, who collectively used 945 stickers over 7 days, most of which were emojis. Emojis were both positively and negatively valanced. Participants took a mean of 9 photos over 7 days and completed workbook questions regarding current PA and PA goals. Themes within the photos included family, specific locations, everyday objects, religion, and friends. Themes within the written portions of the workbook included family, chores and obligations, health, personal reflection, hobbies, and shopping. Conclusions The materials provided allowed breast cancer survivors to successfully use NV techniques to reflect on their PA data and behavior. These techniques show promise for promoting integrated regulation in activity monitoring interventions. Trial registration This study was funded by the National Cancer Institute ( R21CA218543 ) beginning July 1, 2018.

This research mainly focused on the leaf color change and photosystem function differentiation between Loropetalum chinense and its variety L. chinense var. rubrum under heat stress, which were tightly concerned about their ornamental traits and growth. L. chinense ‘Xiangnong Xiangyun’ (X) and L. chinense var. rubrum ‘Xiangnong Fendai’ (F) and L. chinense var. rubrum ‘Hei Zhenzhu’ (H) were chosen to be experimented on to investigate whether leaf color morphology and pigment composition could influence the adaptability of plants to high temperature in order to select foliage plants which posses stable leaf color and better adaptability for hot regions. The plants were cultured in hot environment (40 °C/33 °C, day/night) and normal environment (25 °C/18 °C, day/night). Phenotype and anatomic observation of three cultivars were made and leaf color indices and pigment contents were measured. During the experiment, H and F gradually turned green, total anthocyanins contents significantly decreased in them, however, chlorophyll b contents increased in all three cultivars. In addition, the initial fluorescence (Fo) decreased in X, while increased in H and F. For the maximum fluorescence (Fm) and maximum photochemical efficiency of PSII (Fv/Fm), they only increased in H and decreased in both F and X. The non-photochemical chlorophyll fluorescence quenching (NPQ) also increased in H and decreased in F. For X, it increased at first then gradually decreased. The coefficient of photochemical quenching all increased at first then gradually decreased. Correlation analysis between showed that there was relatively strong connection between anthocyanins, flavonoids and chlorophyll fluorescence parameters, especially NPQ, proved anthocyanins and flavonoids might not only involved in enriching leaf color, but also interfered with the protection of photosystem. Generally speaking, we found higher anthocyanin and flavonoids content level not only dramatically enriched the leaf color of L. chinense var. rubrum cultivars, but also offered more potential antioxidant to keep their normal growth when encountered heat stress.

Summary: The SARS-CoV-2 Omicron variant of concern (VoC) and its sublineages contain 31–36 mutations in spike and escape neutralization by most therapeutic antibodies. In a pseudovirus neutralization assay, 66 of the nearly 400 candidate therapeutics in the Coronavirus Immunotherapeutic Consortium (CoVIC) panel neutralize Omicron and multiple Omicron sublineages. Among natural immunoglobulin Gs (IgGs), especially those in the receptor-binding domain (RBD)-2 epitope community, nearly all Omicron neutralizers recognize spike bivalently, with both antigen-binding fragments (Fabs) simultaneously engaging adjacent RBDs on the same spike. Most IgGs that do not neutralize Omicron bind either entirely monovalently or have some (22%–50%) monovalent occupancy. Cleavage of bivalent-binding IgGs to Fabs abolishes neutralization and binding affinity, with disproportionate loss of activity against Omicron pseudovirus and spike. These results suggest that VoC-resistant antibodies overcome mutagenic substitution via avidity. Hence, vaccine strategies targeting future SARS-CoV-2 variants should consider epitope display with spacing and organization identical to trimeric spike.

Background: Intimate partner violence (IPV) is associated with suboptimal HIV treatment outcomes, but its distribution and risk factors among certain subpopulations of people living with HIV in resource-limited settings are not well known. We examined the prevalence, incidence, and recurrence of IPV and its association with adverse childhood experiences (ACEs) among pregnant/breastfeeding women living with HIV in Malawi. Methods: This study used longitudinal data for 455 pregnant women living with HIV continuously enrolled in the VITAL Start trial. IPV was assessed at baseline and months 1, 6, and 12 using the widely validated WHO IPV survey. Forms of IPV assessed were physical IPV, emotional IPV, and sexual IPV measured as prevalence, incidence, and recurrence. ACE histories were assessed using WHO’s ACE International Questionnaire (ACE-IQ) tool. Logistic and log-binomial regressions were used in multivariable analyses that controlled for factors such as depression and alcohol use. Results: Participants’ mean age was 27.6 ± 5.7 years. Forty-three percent (43%) reported IPV prevalence, 13% reported IPV incidence, and another 13% reported IPV recurrence, with emotional IPV being the most commonly reported IPV type. Over 96% reported experiencing ⩾1 ACE. In regression analysis, cumulative ACE scores were significantly associated with IPV prevalence and IPV recurrence and in both cases, the magnitude of association was greatest for sexual IPV compared with physical IPV and emotional IPV. ACE scores were not significantly associated with IPV incidence. Conclusions: IPV is highly prevalent among pregnant women living with HIV and continues to occur throughout the pregnancy and postpartum period; its graded relationship with ACEs is a concern in resource-limited settings where HIV/AIDS remains a public health concern. Strategies aimed to address the needs of pregnant/breastfeeding women living with HIV may benefit from the regular screening of this population for IPV and ACE, including in antenatal care clinics.

IntroductionLoropetalum chinense var. rubrum blooms 2-3 times a year, among which the autumn flowering period has great potential for exploitation, but the number of flowers in the autumn flowering period is much smaller than that in the spring flowering period.MethodsUsing ‘Hei Zhenzhu’ and ‘Xiangnong Xiangyun’ as experimental materials, the winter growth environment of L. chinense var. rubrum in Changsha, Hunan Province was simulated by setting a low temperature of 6-10°C in an artificial climate chamber to investigate the effect of winter low temperature on the flowering traits and related gene expression of L. chinense var. rubrum.ResultsThe results showed that after 45 days of low temperature culture and a subsequent period of 25°C greenhouse culture, flower buds and flowers started to appear on days 24 and 33 of 25°C greenhouse culture for ‘Hei Zhenzhu’, and flower buds and flowers started to appear on days 21 and 33 of 25°C greenhouse culture for ‘Xiangnong Xiangyun’. The absolute growth rate of buds showed a ‘Up-Down’ pattern during the 7-28 days of low temperature culture; the chlorophyll fluorescence decay rate (Rfd) of both materials showed a ‘Down-Up-Down’ pattern during this period. The non-photochemical quenching coefficient (NPQ) showed the same trend as Rfd, and the photochemical quenching coefficient (QP) fluctuated above and below 0.05. The expression of AP1 and FT similar genes of L. chinense var. rubrum gradually increased after the beginning of low temperature culture, reaching the highest expression on day 14 and day 28, respectively, and the expression of both in the experimental group was higher than that in the control group. The expressions of FLC, SVP and TFL1 similar genes all decreased gradually with low temperature culture, among which the expressions of FLC similar genes and TFL1 similar genes in the experimental group were extremely significantly lower than those in the control group; in the experimental group, the expressions of GA3 similar genes were all extremely significantly higher than those in the control group, and the expressions all increased with the increase of low temperature culture time.DiscussionWe found that the high expression of gibberellin genes may play an important role in the process of low temperature promotion of L. chinense var. rubrum flowering, and in the future, it may be possible to regulate L. chinense var. rubrum flowering by simply spraying exogenous gibberellin instead of the promotion effect of low temperature.

The basic helix–loop–helix (bHLH) transcription factor family is the second-largest transcription factor family in plants. Members of this family are involved in the processes of growth and development, secondary metabolic biosynthesis, signal transduction, and plant resistance. Loropetalum chinense var. rubrum is a critical woody plant with higher ornamental and economic values, which has been used as ornamental architecture and traditional Chinese herbal medicine plants. However, the bHLH transcription factors in Loropetalum chinense var. rubrum (L. chinense var. rubrum) have not yet been systematically demonstrated, and their role in the biosynthesis of anthocyanin is still unclear. Here, we identified 165 potential LcbHLHs genes by using two methods, and they were unequally distributed on chromosomes 1 to 12 of the genome of L. chinense var. rubrum. Based on an evolutionary comparison with proteins from Arabidopsis and Oryza sativa, these bHLH proteins were categorized into 21 subfamilies. Most LcbHLHs in a particular subfamily had similar gene structures and conserved motifs. The Gene Ontology annotation and Cis-elements predicted that LcbHLHs had many molecular functions and were involved in processes of plant growth, including the biosynthesis of flavonoids and anthocyanins. Transcriptomic analysis revealed different expression patterns among different tissues and cultivars of L. chinense var. rubrum. Many LcbHLHs were expressed in the leaves, and only a few genes were highly expressed in the flowers. Six LcbHLHs candidate genes were identified by bioinformatics analysis and expression analysis. Further Real-time quantitative PCR analysis and protein interaction network analysis showed that LcbHLH156, which is one of the candidate proteins belonging to the IIIf subfamily, could interact with proteins related to anthocyanin synthesis. Therefore, LcbHLH156 was transiently expressed in L. chinense var. rubrum to verify its function in regulating anthocyanin synthesis. Compared with the control group, red pigment accumulation appeared at the wound after injection, and the total anthocyanin content increased at the wound of leaves. These results lay a foundation for the research of the regulation mechanism of leaf colors in L. chinense var. rubrum and also provide a basis for the function of the LcbHLH family.

For farmers, the more fragile the state of the ecology becomes, the more their awareness of the need for environmental protection grows. China’s Grain for Green Project (G.G.P.) policy of returning farmland to forests and grassland, as an external shock to the environment, has sparked people’s ecological aspirations. Many people have noticed the phenomenon of ecosystem degradation and overlapping poverty. Analyzing the environmental and income changes brought about by the G.G.P., and this study considers farmers’ self-selection problems due to their lack of subjective thinking regarding this initiative. Our study aims to fill this gap by using a forest–grass model to assess the level of farmers’ ecological aspirations in ecologically vulnerable areas of Xinjiang, China. This article is based on aspiration theory and a theoretical model assessing the economic impact of ecological aspiration on the G.G.P. in China. The results show that farmers’ ecological aspirations can increase their enthusiasm to participate in the G.G.P. Under counterfactual conditions, participation in the G.G.P. initially reduces farmers’ total income to a certain extent; however, in the long run, it can significantly increase the total income of farmers. When the intermediary effect is used to analyze the economic effect of ecological aspiration on returning farmland to forest, it is found that farmers’ ecological aspirations affect household income by influencing income expectations. Our findings have essential practical implications and provide an important reference for consolidating poverty alleviation efforts and effectively promoting rural revitalization. In addition, the results suggest a way to achieve the goals of carbon peak and carbon neutrality, and it is necessary for building environmental-friendly regions.

The local rise in urban temperature is increasingly exacerbated due to the combined effect of urban heat islands and global climate change. Numerous studies have shown that green roofs (GRs) have great potential for facilitating urban heat mitigation. However, little is known about whether such cooling effects can be achieved under extreme heat conditions. With the expected occurrence of more extreme heat events under climate change, such understanding is crucially important for the effective design of heat mitigation. This study aims to fill this gap by investigating the pedestrian-level cooling effect of GR under two weather conditions (i.e., typical summer weather conditions and extreme heat conditions). This research employed a three-dimensional simulation model, ENVI-met, to simulate pedestrian-level air temperature for three typical residential areas with different roof heights in Beijing. We conducted the simulations in two different roof scenarios, conventional roofs versus green roofs. The results showed that green roofs could provide large cooling exceeding 0.2°C on downwind sides and in the daytime, although the average cooling intensity was small. The pedestrian-level cooling intensity of GR decreased significantly under extreme heat conditions compared to typical summer weather conditions. It varied diurnally following an inverted W-shape for both weather conditions. Results also showed that the pedestrian-level cooling intensity of GR decreased with the increase in roof height in a nonlinear way and became 0 when roof height reached ∼50 m for both weather conditions. The results of our research can provide important insights for cooling-oriented urban design in the future, as we are expecting such extreme weather conditions nowadays may be the new normal in the future.

The WRKY gene family plays important roles in plant growth and development, as well as in the responses to biotic and abiotic stresses. Loropetalum chinense var. rubrum has high ornamental and medicinal value. However, few WRKY genes have been reported in this plant, and their functions remain unknown. To explore the roles that the WRKY genes play in L. chinense var. rubrum, we identified and characterized 79 LcWRKYs through BLAST homology analysis and renamed them (as LcWRKY1–79) based on their distribution on the chromosomes of L. chinense var. rubrum. In this way, according to their structural characteristics and phylogenetic analysis, they were divided into three groups containing 16 (Group I), 52 (Group II), and 11 (Group III) WRKYs, respectively. LcWRKYs in the same group have similar motifs and gene structures; for instance, Motifs 1, 2, 3, 4, and 10 constitute the WRKY domain and zinc-finger structure. The LcWRKY promoter region contains light response elements (ACE, G-box), stress response elements (TC-rich repeats), hormone response elements (TATC-box, TCA-element), and MYB binding sites (MBS, MBSI). Synteny analysis of LcWRKYs allowed us to establish orthologous relationships among the WRKY gene families of Arabidopsis thaliana, Oryza sativa, Solanum lycopersicum L., Vitis vinifera L., Oryza sativa L., and Zea mays L.; furthermore, analysis of the transcriptomes of mature leaves and flowers from different cultivars demonstrated the cultivar-specific LcWRKY gene expression. The expression levels of certain LcWRKY genes also presented responsive changes from young to mature leaves, based on an analysis of the transcriptome in leaves at different developmental stages. White light treatment led to a significant decrease in the expression of LcWRKY6, 18, 24, 34, 36, 44, 48, 61, 62, and 77 and a significant increase in the expression of LcWRKY41, blue light treatment led to a significant decrease in the expression of LcWRKY18, 34, 50, and 77 and a significant increase in the expression of LcWRKY36 and 48. These results enable a better understanding of LcWRKYs, facilitating the further exploration of their genetic functions and the molecular breeding of L. chinense var. rubrum.

Light quality is a vital environmental signal used to trigger growth and to develop structural differentiation in plants, and it influences morphological, physiological, and biochemical metabolites. In previous studies, different light qualities were found to regulate the synthesis of anthocyanin. However, the mechanism of the synthesis and accumulation of anthocyanins in leaves in response to light quality remains unclear. In this study, the Loropetalum chinense var. rubrum “Xiangnong Fendai” plant was treated with white light (WL), blue light (BL), ultraviolet-A light (UL), and blue light plus ultraviolet-A light (BL + UL), respectively. Under BL, the leaves were described as increasing in redness from “olive green” to “reddish-brown”. The chlorophyll, carotenoid, anthocyanin, and total flavonoid content were significantly higher at 7 d than at 0 d. In addition, BL treatment also significantly increased the accumulation of soluble sugar and soluble protein. In contrast to BL, ultraviolet-A light increased the malondialdehyde (MDA) content and the activities of three antioxidant enzymes in the leaves, including catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD), in varying degrees over time. Moreover, we also found that the CRY-like gene, HY5-like gene, BBX-like gene, MYB-like gene, CHS-like gene, DFR-like gene, ANS-like gene, and UFGT-like gene were significantly upregulated. Furthermore, the SOD-like, POD-like, and CAT-like gene expressions related to antioxidase synthesis were found under ultraviolet-A light conditions. In summary, BL is more conducive to reddening the leaves of “Xiangnong Fendai” and will not lead to excessive photooxidation. This provides an effective ecological strategy for light-induced leaf-color changes, thereby promoting the ornamental and economic value of L. chinense var. rubrum.

The Loropetalum chinense and Loropetalum chinense var. rubrum are typical as well as traditional ornamental and Chinese herbal medicines in Asia; however, more information is needed on the mechanisms underlying their flower coloring. Here, we profiled the flavonoid metabolome and carried out full-length sequencing in addition to transcriptome analyses to investigate the flavonoid biosynthesis and global transcriptome changes among different petal coloring cultivars of L. chinense and L. chinense var. rubrum. The total anthocyanins in addition to the RHSCC values and CIE 1976 L*a*b* values of petals were highly consistent with petal color. Moreover, a total of 207 flavonoid components were identified. Of these, 13 flavonoid compounds were considered significantly different expression compounds highly consistent with color information in the 4 samples. Meanwhile, the first reference full-length transcriptome of L. chinense var. rubrum was built, which had 171,783 high-quality nonredundant transcripts with correcting with next-generation sequencing (NGS). Among them, 52,851 transcripts were annotated in the seven databases of NR, KOG, GO, NT, Pfam, Swiss-Port, and KEGG. Combined with NGS analyses, the DETs involved in flavonoids and anthocyanins contributed greatest to the flower coloring. Additionally, the different expressions of eight LcDFRs and four LcANS genes were positively correlated with flavonoid biosynthesis, and the four LcBZ1 as well as one Lc3Mat1 were positively correlated with the content of seven anthocyanins revealed by coupling with metabolomics and transcriptomics analyses. Together, these results were used to mine candidate genes by analyzing flower coloring changes at comprehensive metabolic and transcriptomic levels in L. chinense and L. chinense var. rubrum.

“Pruning” is a simple and efficient way to control the flowering period, but it is rarely used in perennial woody ornamental plants. In this paper, Loropetalum chinense var. rubrum was pruned in different degrees, and the relationship between pruning intensity and flowering number, and flowering time and chlorophyll fluorescence parameters were compared. After statistics, it was found that pruning could advance blossoms of L. chinense var. rubrum; also, light and heavy cutting could both obtain a larger number of flowers. In addition, through correlation analysis, it was found that during the flowering period, the Rfd parameter of the unpruned treatment had a very significant positive correlation with the number of flowers FN, which was 0.81. In other pruning treatment groups, Rfd and FN also presented a certain positive correlation, indicating that the Rfd parameter can be used to predict the number of flowers during the flowering process of L. chinense var. rubrum. The research results provided a new idea for the regulation of the flowering period of L. chinense var. rubrum and other woody ornamental plants and laid the foundation for the diversified application of L. chinense var. rubrum.

Salmonella enterica serovar Gallinarum (S. Gallinarum) is a host-specific pathogen causing fowl typhoid, a severe systemic infection in poultry, which leads to substantial economic losses due to high morbidity and mortality in many developing countries. However, less is known about the pathogenic characteristics and mechanism of S. Gallinarum-induced systemic infection in chickens. In this study, we deleted the S. Gallinarum UDP-N-acetylglucosamine-1-phosphate transferase gene, which contributes to the biosynthesis of enterobacterial common antigen (ECA), and studied the pathogenicity of this wecB::Cm strain in a chicken model of systemic infection. The wecB::Cm mutant strain showed comparable growth but lower resistance to bile acid and nalidixic acid than the wild-type strain in vitro. In the oral infection model of chickens, the virulence of the wecB::Cm strain was significantly attenuated in vivo. Chickens infected with wild-type strain showed typical clinical signs and pathological changes of fowl typhoid and died between 6 and 9 days post-infection, and the bacteria rapidly disseminated to systemic organs and increased in the livers and spleens. In contrast, the wecB::Cm mutant strain did not cause chicken death, there were no significant clinical changes, and the bacterial numbers in the liver and spleen of the chickens were significantly lower than those of the chickens infected with the wild-type strain. In addition, the expression of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and CXCLi1 in the livers of wecB::Cm-infected chickens was significantly lower than that of the chickens infected with the wild-type strain. Furthermore, the attenuated wecB::Cm strain could persistently colonize the liver and spleen at low levels for up to 25 days post-infection and could induce a protective immune response in the chickens. These results indicate that the wecB gene is an important virulence factor of S. Gallinarum in the chicken model of systemic infection, and the avirulent wecB::Cm mutant could possibly be used as a live-attenuated vaccine strain for controlling fowl typhoid.

Abstract Background Improving maternal antiretroviral therapy (ART) retention and adherence is a critical challenge facing prevention of mother-to-child transmission (PMTCT) of HIV programs. There is an urgent need for evidence-based, cost-effective, and scalable interventions to improve maternal adherence and retention that can be feasibly implemented in overburdened health systems. Brief video-based interventions are a promising but underutilized approach to this crisis. We describe a trial protocol to evaluate the effectiveness and implementation of a standardized educational video-based intervention targeting HIV-infected pregnant women that seeks to optimize their ART retention and adherence by providing a VITAL Start (Video intervention to Inspire Treatment Adherence for Life) before committing to lifelong ART. Methods This study is a multisite parallel group, randomized controlled trial assessing the effectiveness of a brief facility-based video intervention to optimize retention and adherence to ART among pregnant women living with HIV in Malawi. A total of 892 pregnant women living with HIV and not yet on ART will be randomized to standard-of-care pre-ART counseling or VITAL Start. The primary outcome is a composite of retention and adherence (viral load

According to the solar-blind characteristic of the pantograph arc spectrum distribution, an arc detection method based on the photoelectric conversion mechanism for urban rail was proposed, and the design of each part of the arcing detection system was completed. Through the analysis of arc spectral distribution, the 275-285 nm band was determined as the detection characteristic waveband. The optical acquisition system located on the roof of the train collects the arc characteristic light and transmits it to the photoelectric conversion module, which converts the received optical signal into the corresponding current signal linearly. After amplification, comparison and screening in this module, the optical signal is sent to the data processing module for output display. Finally, a field test conducted on an urban rail transit line shows that this arc detection system can effectively detect the pantograph arc phenomenon and reflect the arc intensity linearly avoiding the influence from natural light, train load and train running direction.

Biochar is increasingly being used for soil improvement, but the effects on microbial diversity in soil are still ambiguous due to contrasting results reported in the literature. We conducted a meta-analysis to clarify the effect of biochar addition on soil bacterial and fungal diversity with an increase in Shannon or Chao1 index as the outcome. Different experimental setups, quantitative levels of biochar addition, various biochar source materials and preparation temperatures, and the effect of natural precipitation in field experiments were the investigated variables. From a total of 95 publications identified for analysis, 384 datasets for Shannon index and 277 datasets for Chao1 index were extracted that described the bacterial diversity in the soils, of which field experiments and locations in China dominated. The application of biochar in soil significantly increased the diversity of soil bacteria but it had no significant effect on the diversity of fungi. Of the different experimental setups, the largest increase in bacterial diversity was seen for field experiments, followed by pot experiments, but laboratory and greenhouse settings did not report a significant increase. In field experiments, natural precipitation had a strong effect, and biochar increased bacterial diversity most in humid conditions (mean annual precipitation, MAP > 800 mm), followed by semi-arid conditions (MAP 200–400 mm). Biochar prepared from herbaceous materials was more effective to increase bacterial diversity than other raw materials and the optimal pyrolysis temperature was 350–550 °C. Addition of biochar at various levels produced inconclusive data for Chao1 and Shannon indices, and its effect was less strong than that of the other assessed variables.

The pantograph–catenary arc of urban rail has the characteristic of high temperature, which directly acts on the surface of the pantograph–catenary system, will seriously ablate pantograph and contact line, and affect the flow of the pantograph–catenary system. In this paper, based on MHD, a mathematical model of the arcing of urban rail pantograph–catenary system is established. COMSOL finite element software was used to simulate the arc temperature field of the pantograph–catenary arc. Through the temperature distribution cloud diagram and related images, the relationship between the arc central temperature, the duration, and the gap of the pantograph arc were studied. It is found that the arc temperature increases with the increase in arc duration when the arc gap is fixed. When the arc duration is fixed, the arc center temperature changes inversely with the increase in the arc gap. The feasibility of the simulation model is verified by the pantograph–catenary arc experiment platform. The research conclusion of this paper can provide a certain basis for the research of arc erosion on the surface of the pantograph–catenary system.

Loropetalum chinense var. rubrum is a common landscape plant. Because of the preference for the ‘red leaf’ trait, the ‘flower color’ trait was ignored in breeding, and the genetic diversity of L. chinense var. rubrum was replaced by a few genotypes. Therefore, the potential value of flower color traits was affected, and the genetic diversity was not fully exploited. In this study, we utilized a cultivar with mosaic-colored flowers and leaves and observed 15 phenotypic traits in its flower organs and its progeny, as well as a total of 60 different flower color materials. We analyzed the variation characteristics and diversity of flower colors, and qualitatively described and preliminarily classified flower colors using the ISCC-NBS and CIELab systems to explore the correlation with the flower color phenotype from the distribution and content of anthocyanins. The phenotypic diversity of the flower organs was enriched, and genetic differences in flower color were significant for the L.chinense var. rubrum, with most of the 15 phenotypic traits showing significant positive correlations, and the most critical phenotypes are sepal, petal and nectary color, as well as petal length. According to the CIELab color system and anthocyanin content and distribution characteristics, it is considered more accurate and convenient to classify the color phenotypes of L. chinense var. rubrum flowers into five categories. In this study, for the first time, the flower organ phenotype of L. chinense var. rubrum has been systematically analyzed, and it is explored as a reference method for breeding new cultivars of a diverse range of colors in L. chinense var. rubrum.

Background: Recurrent implantation failure (RIF) remains a critical and challenging problem in assisted reproductive technology mainly due to impaired decidualization. The endocytic and transcytotic activity in the endometrium are crucial for decidualization. The most representative endocytic gene is the C-terminal Eps15 homology domain-containing 1 (EHD1), but whether EHD1-mediated endocytic function is responsible for embryo implantation during decidualization remains unclear. Methods: A transcriptomic analysis was performed to evaluate the differentially expressed genes between the fertile control and RIF group. The expression and location of EHD1 in endometrial tissues were further examined by IHC, qRT-PCR and Western blotting. The transduction of an EHD1 recombinant adenovirus into human endometrial stromal cells was performed to investigate relevant decidualization marker genes. Additionally, a microarray analysis following the adenovirus-mediated overexpression of EHD1 was conducted to identify EHD1-related changes in HESCs, and the potential molecular mechanisms were further confirmed through immunofluorescence and coimmunoprecipitation analyses. Findings: An RNA-seq analysis demonstrated that EHD1 expression was significantly higher in the mid-secretory endometrium of the RIF group than in that of the fertile control group. The analysis of the menstrual cycle showed that expression of EHD1 increased in the mid-proliferative phase and showed a gradual decrease in the mid-secretory and decidual phases. Furthermore, EHD1 overexpression impaired decidualization by suppressing the expression of prolactin and insulin-like growth factor binding protein-1 and the formation of the cytoskeleton. The mechanistic analysis revealed the EHD1 regulated LRP5/6 protein function through the endocytic pathway, and subsequently suppressed the Wnt4/β-catenin pathway during decidualization. In addition, a Wnt4 agonist improved an impaired decidualization process. Interpretation: Regulation of the EHD1-Wnt4 pathway might serve as a promising therapeutic strategy for improving endometrial receptivity in RIF women. Keywords: EHD1, Decidualization, RIF, Wnt4

Dendrobium officinale Kimura et Migo, a highly valued Chinese herbal medicine, is on the verge of extinction in the wild, and is not cultivated efficiently. In this study, we explored the possibility that orchid mycorrhizal fungi (OMF) might improve the growth and cultivation of D. officinale. Serendipita sp., Tulasnella calospora and Tulasnella asymmetrica isolated from three different orchids were co-cultured with sterile seedlings of D. officinale. The seedlings were found to stably coexist with fungi after 60 days of co-culture. The co-culture of T. calospora with plants upregulated the activity of antioxidant enzymes, stimulated the production of osmoregulatory substances and reduced electrical conductivity. Plants with T. calospora had longer roots (141.2%), thicker leaves (58.3%), increased root number (71.4%) and leaf number (11.1%), and increased weight (155.2%) and photosynthetic pigment content (99.6%), relative to controls. The content of total medicinal polysaccharides increased by 42.69 % due to the addition of T. calospora. T. asymmetrica was less effective, followed by Serendipita sp. When T. calospora established a symbiotic relationship with D. officinale, resistance indicators increased. The content of functional components was significantly increased. This study contributes to the protection and commercial reproduction of endangered orchid plants with mycorrhizal technology.

Objective: Randomized clinical trials (RCTs) examining the effects of resveratrol supplementation on liver enzymes in non-alcoholic fatty liver disease (NAFLD) have reported conflicting results. The aim of this systematic review was to summarize evidence of the effects of resveratrol supplementation on alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels in patients with NAFLD by performing a meta-analysis of RCTs. Methods: PubMed, Cochrane Library, Scopus, and Web of Science databases were electronically explored from inception to August 2020 for all relevant studies. Random effect models were used to estimate liver enzymes changes between resveratrol supplementation and control groups by evaluating the weighted mean differences (WMD) with 95 % confidence intervals (CIs). Results: Five trials with a total of 216 patients were included in the meta-analysis. The pooled results showed that resveratrol supplementation did not result in significant changes in serum ALT (WMD= -2.48 IU/L; 95 % CI: -12.30, 7.34; P = 0.62), and AST (WMD = -2.90 IU/L; 95 % CI: -9.77, 3.98; P = 0.40) concentrations. Subgroup analysis revealed a significant reduction in serum ALT and AST concentrations in the participants with mean age 12 weeks and participants with BMI

The filoviruses, including ebolaviruses and marburgviruses, are among the world’s deadliest pathogens. As the only surface-exposed protein on mature virions, their glycoprotein GP is the focus of current therapeutic monoclonal antibody discovery efforts. With recent technological developments, potent antibodies have been identified from immunized animals and human survivors of virus infections and have been characterized functionally and structurally. Structural insight into how the most successful antibodies target GP further guides vaccine development. Here we review the recent developments in the identification and characterization of neutralizing antibodies and cocktail immunotherapies.

Urban community gardens (UCGs), greenspace cultivated and managed for vegetables by local communities, provide substantial ecosystem services (ES) and are warmly welcomed by residents. However, they also have many ecosystem disservices (EDS) and are almost always refused by the decision-makers of the government, especially in China. Better understanding the residents’ perceived ES and EDS and the impact on the behavioral intention (BI) toward UCGs is of great value to solve the conflicts between residents and the government concerning UCGs and to develop sustainable UCGs. Following the theory of planned behavior (TPB), we measured perceived ES/EDS, attitudes (ATT), perceived behavioral control (PBC), subjective norm (SN), and BI of 1142 residents in Changsha, China, and investigated their direct and indirect causal relationships using structural equation modeling (SEM). The results showed that: (1) ATT, PBC, and SN significantly and positively impact the BI of UCGs and together explained 54% of the variation of BI. (2) The extended TPB model with additional components of perceived ED/EDS improved the explanatory ability of the model, explaining 65% of the variance of BI. Perceived ES and perceived EDS showed significant direct positive and negative impacts on UCGs, respectively. They also indirectly impacted BI by influencing ATT, PBC, and SN. The findings of this study can extend our understanding of residents’ attitudes, behavior, and driving mechanism toward UCGs, and can help decision makers to design better policies for UCG planning and management.

Abstract Background Hepatocellular carcinoma (HCC) has limited treatment options in patients with advanced stage disease and early detection of HCC through surveillance programs is a key component towards reducing mortality. The current practice guidelines recommend that high-risk cirrhosis patients are screened every six months with ultrasonography but these are done in local hospitals with variable quality leading to disagreement about the benefit of HCC surveillance. The well-established diagnostic biomarker α-Fetoprotein (AFP) is used widely in screening but the reported performance varies widely across studies. We evaluate two biomarker screening approaches, a six-month risk prediction model and a parametric empirical Bayes (PEB) algorithm, in terms of their ability to improve the likelihood of early detection of HCC compared to current AFP alone when applied prospectively in a future study. Methods We used electronic medical records from the Department of Veterans Affairs Hepatitis C Clinical Case Registry to construct our analysis cohort, which consists of serial AFP tests in 11,222 cirrhosis control patients and 902 HCC cases prior to their HCC diagnosis. The six-month risk prediction model incorporates routinely measured laboratory tests, age, the rate of change in AFP over the past year with the current AFP. The PEB algorithm incorporates prior AFP screening values to identify patients with a significant elevated level of AFP at their current screen. We split the analysis cohort into independent training and validation datasets. All model fitting and parameter estimation was performed using the training data and the algorithm performance was assessed by applying each approach to patients in the validation dataset. Results When the screening-level false positive rate was set at 10%, the patient-level true positive rate using current AFP alone was 53.88% while the patient-level true positive rate for the six-month risk prediction model was 58.09% (4.21% increase) and PEB approach was 63.64% (9.76% increase). Both screening approaches identify a greater proportion of HCC cases earlier than using AFP alone. Conclusions The two approaches show greater potential to improve early detection of HCC compared to using the current AFP only and are worthy of further study.

Lavandin, as an important cash crop, is cultivated in Kunming, Yun-Gui Plateau of China. For the special growing environment, Lavandin was grown here and used to investigate the changes in the yield and chemical compositions of essential oils extracted from the flowers in different seasons. The essential oils were extracted by hydro-distillation and analysis by gas chromatography-mass spectrometry (GC-MS). Results indicated great changes in chemical composition depending on the season of harvesting. The yields of essential oils ranged from 2.0% to 3.8% among the seasons, and the highest yield was in the summer. Chemical composition data showed that the extracted oils were rich in oxygenated monoterpenes (55.4–81.4%), eucalyptol (38.7–49.8%), camphor (8.41–14.26%), α-bisabolol (6.6–25.5%), and linalool (4.6–12.5%). The contents of eucalyptol and α-bisabolol changed in a contrary trend with seasonal variations. The results provided new insight for Chinese Lavandin germplasm to be used in application and development, and reference to the researcher, the farmer, and investor for sustainable industrialization of the plant grown in the Yun-Gui Plateau of China, but also the similar plateau area of the sustainable developments.

Abstract Background Extracts of plants have been considered as sources of natural antioxidant agents. In this study, we aimed to explore the antioxidant capacity of the aqueous root extract of Asparagus cochinchinensis (Lour.) Merr. Methods Using vitamin C (Vc) as a positive control, we analyzed the aqueous root extract of A. cochinchinensis free radical scavenging ability in vitro. We also established a mouse aging model using D-galactose and then treated it with aqueous root extract or Vc. The blood cell count and superoxide dismutase (SOD), catalase (CAT), and nitric oxide synthase (NOS) activities as well as malondialdehyde (MDA) and nitric oxide (NO) contents were measured; pathological examination of tissues was performed; and SOD, glutathione peroxidase (GPX), and NOS expression levels in the serum, liver, and brain tissues were investigated. Results In vitro, compared with the antioxidant Vc, the aqueous root extract showed similar 1,1-Diphenyl-2-picrylhydrazyl radical and 3-ethylbenzothiazoline-6-sulfonic·scavenging activities and even significantly increased superoxide anion (p < 0.05) and hydroxyl radical (OH) (p < 0.01) scavenging activities. The aqueous extract significantly increased the white blood cell count as well as enhanced SOD, CAT, and NOS activities (p < 0.01) in aging mice. In addition, the aqueous extract increased the NO content (p < 0.05) and reduced the MDA content (p < 0.05). Conclusions The aqueous root extract of A. cochinchinensis showed as strong antioxidant ability as Vc and might prevent aging by reducing radicals.

An algorithm to predict train wheel diameter based on Gaussian process regression (GPR) optimized using a fast simulated annealing algorithm (FSA-GPR) is proposed in this study to address the problem of dynamic decrease in wheel diameter with increase in mileage, which affects the measurement accuracy of train speed and location, as well as the hyper-parameter problem of the GPR in the traditional conjugate gradient algorithm. The algorithm proposed as well as other popular algorithms in the field, such as the traditional GPR algorithm, and GPR algorithms optimized using the artificial bee colony algorithm (ABC-GPR) or genetic algorithm (GA-GPR), were used to predict the wheel diameter of a DF11 train in a section of a railway during a period of major repairs. The results predicted by FSA-GPR was compared with other three algorithms as well as the real measured data from RMSE, MAE, R2 and Residual value. And the comparisons showed that the predictions obtained from the GPR optimized using FSA algorithm were more accurate than those based on the others. Therefore, this algorithm can be incorporated into the vehicle-mounted speed measurement module to automatically update the value of wheel diameter, thereby substantially reducing the manual work entailed therein and improving the effectiveness of measuring the speed and position of the train.

ContextHigh rates of burnout have been reported in low and medium income countries and can detrimentally impact healthcare delivery. Understanding factors associated with burnout amongst health care workers providing HIV care may help develop interventions to prevent/treat burnout.ObjectivesWe sought to understand factors associated with burnout amongst health care workers providing HIV care in Malawi.MethodsThis was a sub-study of a larger cross-sectional study measuring burnout prevalence amongst a convenience sample of healthcare workers providing HIV care in 89 health facilities in eight districts in Malawi. Burnout was measured using the Maslach Burnout Inventory. Anonymously administered surveys included questions about sociodemographics, work characteristics (work load, supervisor support, team interactions), depression, life stressors, assessment of type D personality, and career satisfaction. We performed univariable and multivariable regression analyses to explore associations between variables and burnout.ResultsWe received 535 responses (response rate 99%). Factors associated with higher rates of burnout on multivariable regression analyses included individual level factors: male gender (OR 1.75 [CI 1.17, 2.63]; p = 0.007), marital status (widowed or divorced) (OR 3.24 [CI 1.32, 7.98]; p = 0.011), depression (OR 3.32 [CI 1.21, 9.10]; p = 0.020), type D personality type (OR 2.77 [CI 1.50, 5.12]; p = 0.001) as well as work related factors: working at a health center vs. a rural hospital (OR 2.02 [CI 1.19, 3.40]; p = 0.009); lack of a very supportive supervisor (OR 2.38 [CI 1.32, 4.29]; p = 0.004), dissatisfaction with work/team interaction (OR 1.76 [CI 1.17, 2.66]; p = 0.007), and career dissatisfaction (OR 0.76 [CI 0.60, 0.96]; p = 0.020).ConclusionThis study identified several individual level vulnerabilities as well as work related modifiable factors. Improving the supervisory capacity of health facility managers and creating conditions for improved team dynamics may help reduce burnout amongst healthcare workers proving HIV care in Malawi.

Summary: Synthetically engineered DNA-encoded monoclonal antibodies (DMAbs) are an in vivo platform for evaluation and delivery of human mAb to control against infectious disease. Here, we engineer DMAbs encoding potent anti-Zaire ebolavirus (EBOV) glycoprotein (GP) mAbs isolated from Ebola virus disease survivors. We demonstrate the development of a human IgG1 DMAb platform for in vivo EBOV-GP mAb delivery and evaluation in a mouse model. Using this approach, we show that DMAb-11 and DMAb-34 exhibit functional and molecular profiles comparable to recombinant mAb, have a wide window of expression, and provide rapid protection against lethal mouse-adapted EBOV challenge. The DMAb platform represents a simple, rapid, and reproducible approach for evaluating the activity of mAb during clinical development. DMAbs have the potential to be a mAb delivery system, which may be advantageous for protection against highly pathogenic infectious diseases, like EBOV, in resource-limited and other challenging settings. : Monoclonal antibodies are an important approach for emerging infectious disease prevention. Patel et al. demonstrate engineering and in vivo delivery of DNA-encoded monoclonal antibodies (DMAbs) targeting the Zaire ebolavirus (EBOV) glycoprotein. DMAbs protect against lethal mouse-adapted EBOV and are useful for rapid evaluation of fully human mAbs in live animal models. Keywords: DNA-encoded monoclonal antibody, DMAb, monoclonal antibody, Zaire ebolavirus, EBOV, Ebola virus disease, glycoprotein, immunoprophylaxis, DNA, electroporation