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BackgroundIn previous observational studies and meta-analyses, childhood attention deficit hyperactivity disorder (ADHD) is found to have a significant association with screen time. However, the causal associations between them remain unclear.MethodThis study performed a bidirectional two-sample Mendelian randomization (MR) analysis to confirm the causality between screen time and childhood ADHD. Large-scale genome-wide association studies (GWAS) datasets derived from the Psychiatric Genomics Consortium (PGC) and the UK Biobank were used to identify single nucleotide polymorphisms (SNPs) associated with exposure and outcome. Four categories of datasets were selected to represent screen time. The SNPs that are significantly associated with exposure data (P < 5e-08) and have a strong correlation with the exposure in the F-statistic (F > 10) were selected as instrumental variables. This study also used the PhenoScanner V2 database and the LDlink webtool to exclude confounding factors, and the MR-PRESSO method (p < 0.05) was employed to eliminate outliers with bias. Five commonly used methods were employed to assess the interaction and the Inverse Variance Weighted (IVW) method was utilized as the primary basis for determining the MR estimates in this study.ResultsThe MR analysis revealed that the length of mobile phone use (OR, 1.848; 95% CI, 1.3360-2.5558; p=2.07e-4) and the time spent watching television (OR, 2.104; 95% CI, 1.3958-3.1703; p=3.8e-4) increased the risk of childhood ADHD. Although the causal relationships were exclusively identified through the IVW and weighted median methods, the results retained their statistical significance following correction. In the reverse analysis, no evidence was found to support an effect of childhood ADHD on screen time. The sensitivity analysis conducted on the significant findings revealed no evidence of horizontal pleiotropy or heterogeneity.ConclusionThis study provides some evidence for the causality of screen time and childhood ADHD. Given the limitations of our study, further research is required to comprehensively investigate this relationship.

Background: Cognitive decline among people living with HIV (PLWH) is growing concern as world populations become increasing older including higher proportions of PLWH. It is vitally important to understand psychosocial predictors of age-related cognitive decline men who have sex with men (MSM) living with HIV. Objectives: The current study seeks to examine psychosocial risk factors the contribute to the risk of age-related cognitive impairment as measured by Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) score in a racially diverse sample of MSM living with HIV. Design: The present analysis utilizes data from the baseline ( n = 196) and 6-month follow-up ( n = 135) time points of a longitudinal cohort study of PLWH. Methods: Using a self-report survey, we examine the associations between psychosocial predictors (e.g. trauma, mental health, chronic pain, sleep disturbance, etc.) and risk of dementia using the CAIDE risk score. Analyses include linear and logistic regression. Results: In adjusted model stress, chronic pain, Black racial identity, and having a sexual identity that is bisexual or another category are all positively associated with CAIDE scores. Childhood sexual abuse history was negatively associated with CAIDE scores indicating a protective effect. Sleep disorder has a positive association with CAIDE scores after adjusting for the baseline CAIDE scores. Conclusion: These results indicate modifiable correlates of cognitive risk (stress and chronic pain). Interventions should seek to address these comorbid factors including the consideration of minority stress and stigma. Interventions should seek to reach Black and bisexual men living with HIV, including possible cultural tailoring to interventions and messaging. Lastly, future research should examine the impact of variation within childhood sexual abuse histories to better understand their association with cognitive impairment later in life. This may include considering the nature, severity, and potential treatment of trauma symptoms.

Single-screw extruders and injection molding machines are essential equipment in polymer processing. It is of great importance for the optimization of operating parameters and the design of extrusion screw to predict the throughput of an extruder and the metering time of an injection molding machine according to the geometric parameters of the screw, operating parameters, and the rheological behavior of materials. Most polymer melts exhibit non-Newtonian behavior. The lattice Boltzmann method has many advantages in simulating the flow of non-Newtonian fluids. Herein, the dimensionless velocity profiles and dimensionless volumetric flow rate of generalized Newtonian fluids in a screw channel have been studied using the two-relaxation-time lattice Boltzmann method (TRT–LBM). The numerical results of power-law fluids are in good agreement with the analytical solutions, which verifies the validity of TRT–LBM. Through research, the change rule of the dimensionless volumetric flow rate of Bingham fluids with dimensionless pressure gradient has been obtained. It was found that the rheological properties of polymer melts and the dimensionless pressure gradient significantly affect the dimensionless velocity profiles and dimensionless volumetric flow rate. The dimensionless volume flow rate has some unexpected changes with the increase of the dimensionless pressure gradient. This study can provide theoretical guidance for the optimization of operating parameters and the design of extrusion screws.

Intracranial medulloepithelioma is a very rare and highly malignant tumor that is typically diagnosed in childhood and has an inferior prognosis. In the current report, we described a case of fetal intracranial medulloepithelioma that was detected during the third trimester by prenatal ultrasonography, which displayed homogenous echogenicity with well-circumscribed margins and abundant blood flow. On magnetic resonance imaging, it was hyperintense on both T1- and T2-weighted magnetic resonance imaging. The fetal intracranial tumor was progressive, with rapid expansion within 3 weeks. The report aimed to provide knowledge on the clinical characteristics of fetal intracranial medulloepithelioma in prenatal diagnosis, particularly the radiological features.

Verticillium wilt is one of the most crucial diseases caused by Verticillium dahliae that threatens the cotton industry. Statistical results showed that the return of cotton plants infected with V. dahliae to the field might be an essential cause of the continuous aggravation of cotton Verticillium wilt. The correlation among the cotton plants infected with V. dahliae returning to the field, the occurrence of Verticillium wilt, and the number of microsclerotia in rhizosphere soil need further investigation. A potted experiment was carried out to explore the effects of the direct return of cotton plants infected with Verticillium dahliae to the field on the subsequent growth and Verticillium wilt occurrence in cotton. As a risk response plan, we investigated the feasibility of returning dung-sand (i.e., insect excreta) to the field, the dung-sand was from the larvae of Protaetia brevitarsis (Coleoptera: Cetoniidea) that were fed with the V. dahliae–infected cotton plants. The results demonstrated that the return of the entire cotton plants to the field presented a promotional effect on the growth and development of cotton, whereas the return of a single root stubble or cotton stalks had an inhibitive effect. The return of cotton stalks and root stubble infected with V. dahliae increased the risk and degree of Verticillium wilt occurrence. The disease index of Verticillium wilt occurrence in cotton was positively correlated with the number of microsclerotia in the rhizosphere soil. The disease index increased by 20.00%, and the number of soil microsclerotia increased by 8.37 fold in the treatment of returning root stubble infected with V. dahliae to the field. No Verticillium wilt microsclerotia were detected in the feed prepared from cotton stalks and root stubble fermented for more than 5 days or in the transformed dung-sand. There was no risk of inoculation with Verticillium wilt microsclerotia when the dung-sand was returned to the field. The indirect return of cotton plants infected with V. dahliae to the field by microorganism–insect systems is worthy of further exploration plan of the green prevention and control for Verticillium wilt and the sustainable development of the cotton industry.

Objective: The study aimed to examine the dose–response associations between night-sleep duration and depression risk in middle-aged and older adults.Methods: We searched PubMed, Embase, Web of Science, CNKI, VIP, and the Wanfang data knowledge service platforms from inception to 31 July 2022. Cohort and case–control studies assessing the relationship between night-sleep duration and depression were selected. We used the Newcastle–Ottawa scale to assess the quality of the published research. Two researchers carried out data extraction and quality assessment. The restricted cubic spline function and generalized least squares method were used to establish dose–response relationships between sleep duration and depression. We aimed to analyze the estimated effect size presented as the risk ratio (RR) and its 95% confidence interval (CI) using Stata 12.0.Result: Six cohort studies with 33,595 participants were included in this meta-analysis. A U-shaped association between sleep duration and depression risk was revealed. On one hand, compared with 7-h of night sleep, both shorter and longer sleep duration were associated with an increased risk of depression (5 h: risk ratio = 1.09, 95% confidence interval = 1.07–1.12; 6 h: RR = 1.03, 95% CI = 1.02–1.04; 8 h: RR = 1.10, 95% CI = 1.05–1.15; 9 h: RR = 1.31, 95% CI = 1.17–1.47; 10 h: RR = 1.59, 95% CI = 1.31–1.92; non-linear test p < 0.05). On the other hand, an increased risk of depression with shorter sleep duration was observed in middle-aged and older people among the non-Asian population (5 h: RR = 1.09; 95% CI = 1.02–1.17), while both shorter and longer sleep duration can increase the risk of depression among an Asian population (5 h: RR = 1.10, 95% CI = 1.07–1.13; 6 h: RR = 1.04, 95% CI = 1.02–1.05; 8 h: RR = 1.09, 95% CI = 1.05–1.14; 9 h: RR = 1.35, 95% CI = 1.18–1.53; 10 h: RR = 1.70, 95% CI = 1.36–2.12).Conclusion: The lowest-risk onset of depression occurred among middle-aged and older people with 7 h of night sleep, which suggested that shorter and longer night-sleep duration might lead to an increased incidence of depression.Clinical Trial Registration:https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=344052, identifier 344052

Hypertension is the leading preventable risk factor for cardiovascular disease and all-cause mortality worldwide. However, studies have shown increased risk of mortality from heart disease and stroke even within the normal blood pressure (BP) range, starting at BPs above 110–115/70–75 mm Hg. Nutraceuticals, such as vitamins and minerals, have been studied extensively for their efficacy in lowering BP and may be of benefit to the general, normotensive population in achieving optimal BP. Our study investigated the effects of six nutraceuticals (Vitamins: C, D, E; Minerals: Calcium, Magnesium, Potassium) on both systolic blood pressure (SBP) and diastolic blood pressure (DBP) in this population. We performed a systematic review and pairwise meta-analysis for all six supplements versus placebo. Calcium and magnesium achieved significant reductions in both SBP and DBP of −1.37/−1.63 mm Hg and −2.79/−1.56 mm Hg, respectively. Vitamin E and potassium only yielded significant reductions in SBP with values of −1.76 mm Hg and −2.10 mm Hg, respectively. Vitamins C and D were not found to significantly lower either SBP or DBP. Future studies should determine optimal dosage and treatment length for these supplements in the general, normotensive population.

As vibrations caused by the coupling of carriers and tracks could affect the performance of braiding machines a lot, it is necessary to establish the carrier-track contact model and investigate its dynamic characteristics. Therefore, a dynamic model of carrier-track contact model has been developed. Based on the Hertz's law and Newton's law, the dynamical equations of carriers were established. The influence of contact related parameters to the carriers' dynamic characteristics were discussed. Besides, a comparison of contact parameters with different contact models was presented. The results show that although carriers keep a low contact speed, collisions still exist during carriers transferring between tracks. To avoid/decrease collisions and shocks, some methods were proposed, e.g. controlling the angular velocity of horn gears variable, changing the contact surface to have a higher coefficient of restitution and reducing the vibration of frame and tracks, which could be helpful to the design of braiding machines.

Intraductal papillary neoplasm of the bile duct (IPNB) is a rare bile duct tumor characterized by intraductal papillary or villous neoplasms covered by neoplastic epithelium with fine fibrovascular stalks in the dilated bile ducts (1). Its true etiology remains unknown. Herein, we report two cases of IPNB that underwent surgical resection. The first case was a 66-year-old male who complained of upper abdominal pain for three years. We found obstruction of the common bile duct and dilation of the intrahepatic and extrahepatic bile ducts after MRCP. Laparoscopic hepatic segmentectomy (S2, S3, S4), resection of the common bile duct, cholecystectomy, and hepaticojejunostomy were performed. The second case was a 67-year-old male with asymptomatic dilation of the intrahepatic duct. The patient underwent robot-assisted laparoscopic hepatic segmentectomy (S5, S6, S7, S8), resection of the common bile duct, hepaticojejunostomy and cholecystectomy.

Pulmonary atresia with ventricular septal defect (PA/VSD) is a rare congenital heart disease (CHD) characterized by a lack of luminal continuity and blood flow from either the right ventricle or the pulmonary artery, together with VSDs. The prevalence of PA/VSD is about 0.2% of live births and approximately 2% of CHDs. PA/VSD is similar to tetralogy of Fallot (TOF) in terms of structural and pathological characteristics. The pathogenesis of these two CHDs remains incompletely understood. It was previously reported that N‐myc downstream‐regulated gene (NDRG)4 is required for myocyte proliferation during early cardiac development. In the present study, we enrolled 80 unrelated patients with PA/VSD or TOF and identified a probably damaging variant p.T256M of NDRG4. The p.T256M variant impaired the proliferation ability of human cardiac myocytes (hCM). Furthermore, the p.T256M variant resulted in G1 and G2 arrest of hCM, followed by an increase in p27 and caspase‐9 expression. Our results provide evidence that the p.T256M variant in NDRG4 is a pathogenic variant associated with impaired hCM proliferation and cell‐cycle arrest and likely contributes towards the pathogenesis of PA/VSD and TOF.

Somatic mutations are recognized as an important prognostic factor in chronic myelomonocytic leukemia (CMML). However, limited data are available regarding their impact on outcomes after allogeneic hematopoietic cell transplantation (HCT). In this registry analysis conducted in collaboration with the Center for International Blood and Marrow Transplantation Registry database/sample repository, we identified 313 adult patients with CMML (median age: 64 years, range, 28- 77) who underwent allogeneic HCT during 2001-2017 and had an available biospecimen in the form of a peripheral blood sample obtained prior to the start of conditioning. In multivariate analysis, a CMML-specific prognostic scoring system (CPSS) score of intermediate-2 (HR=1.46, P=0.049) or high (HR=3.22, P=0.0004) correlated significantly with overall survival. When the molecularly informed CPSS-Mol prognostic model was applied, a high CPSS-Mol score (HR=2 P=0.0079) correlated significantly with overall survival. The most common somatic mutations were in ASXL1 (62%), TET2 (35%), KRAS/NRAS (33% combined), and SRSF2 (31%). DNMT3A and TP53 mutations were associated with decreased overall survival (HR=1.70 [95% CI: 1.11-2.60], P=0.0147 and HR=2.72 [95% CI: 1.37-5.39], P=0.0042, respectively) while DNMT3A, JAK2, and TP53 mutations were associated with decreased disease-free survival (HR=1.66 [95% CI: 1.11-2.49], P=0.0138, HR=1.79 [95% CI: 1.06-3.03], P=0.0293, and HR=2.94 [95% CI: 1.50-5.79], P=0.0018, respectively). The only mutation associated with increased relapse was TP53 (HR=2.94, P=0.0201). Nonetheless, the impact of TP53 mutations specifically should be interpreted cautiously given their rarity in CMML. We calculated the goodness of fit measured by Harrell’s C-index for both the CPSS and CPSS-Mol, which were very similar. In summary, via registry data we have determined the mutational landscape in patients with CMML who underwent allogeneic HCT, and demonstrated an association between CPSS-Mol and transplant outcomes although without major improvement in the risk prediction beyond that provided by the CPSS.

Abstract Background Conotruncal defects (CTDs) are a type of heterogeneous congenital heart diseases (CHDs), but little is known about their etiology. Increasing evidence has demonstrated that fibroblast growth factor (FGF) 8 and FGF10 may be involved in the pathogenesis of CTDs. Methods The variants of FGF8 and FGF10 in unrelated Chinese Han patients with CHDs (n = 585), and healthy controls (n = 319) were investigated. The expression and function of these patient-identified variants were detected to confirm the potential pathogenicity of the non-synonymous variants. The expression of FGF8 and FGF10 during the differentiation of human embryonic stem cells (hESCs) to cardiomyocytes and in Carnegie stage 13 human embryo was also identified. Results Two probable deleterious variants (p.C10Y, p.R184H) of FGF8 and one deletion mutant (p.23_24del) of FGF10 were identified in three patients with CTD. Immunofluorescence suggested that variants did not affect the intracellular localization, whereas ELISA showed that the p.C10Y and p.23_24del variants reduced the amount of secreted FGF8 and FGF10, respectively. Quantitative RT-PCR and western blotting showed that the expression of FGF8 and FGF10 variants was increased compared with wild-type; however, their functions were reduced. And we found that FGF8 and FGF10 were expressed in the outflow tract (OFT) during human embryonic development, and were dynamically expressed during the differentiation of hESCs into cardiomyocytes. Conclusion Our results provided evidence that damaging variants of FGF8 and FGF10 were likely contribute to the etiology of CTD. This discovery expanded the spectrum of FGF mutations and underscored the pathogenic correlation between FGF mutations and CTD.

BackgroundPulmonary atresia (PA) is a kind of congenital heart disease characterized by right ventricular outflow tract obstruction. It is divided into PA with intact ventricular septum (PA/IVS) whose favorable form is pulmonary valvular stenosis (PS), and PA with ventricular septal defect (PA/VSD) whose favorable form is tetralogy of Fallot (TOF). Due to limitations in genetics etiology, whole-exome sequencing (WES) was utilized to identify new variants associated with the diseases.MethodsThe data from PS-PA/IVS (n = 74), TOF-PA/VSD (n = 100), and 100 controls were obtained. The common sites between PS and PA/IVS, PA/VSD and TOF, were compared. The novel rare damage variants, and candidate genes were identified by gene-based burden analysis. Finally, the enrichment analysis of differential genes was conducted between case and control groups.ResultsSeventeen rare damage variants located in seven genes were predicted to be associated with the PS through burden analysis. Enrichment analysis identified that the Wnt and cadherin signaling pathways were relevant to PS-PA/IVS.ConclusionThis study put forth seven candidate genes (APC, PPP1R12A, PCK2, SOS2, TNR, MED13, and TIAM1), resulting in PS-PA/IVS. The Wnt and cadherin signaling pathways were identified to be related to PS-PA/IVS by enrichment analysis. This study provides new evidence for exploring the genetic mechanism of PS-PA/IVS.

This work studies the electromagnetic field of a radiofrequency (RF) antenna on 7-inch liquid crystal display (LCD) and presents a new approach where the RF antenna is designed on LCD. This approach takes the magnetic field effect of LCD as an input parameter when building and simulating antenna models using the software Ansoft HFSS. After obtaining the PCB of the antenna, place the antenna on LCD, so that the antenna and LCD overlap up and down and measure the equivalent physical parameters as a whole. Last, use the vector network analyzer and Smith circle graph to tune the antenna system for completing the impedance matching of the whole system. This method breaks through the limitation that the card swiping area and the display area cannot be in the same area due to electromagnetic interference. It has changed the appearance design concept of the mobile point of sale (POS), and the antenna size can be 20%–100% of the POS display area. A contactless card read-write experiment for the proposed method has been carried out. Results showed the return loss is less than −30 dB, and the effective read-write distance of the antenna can reach about 5 cm. This design method provides a broader application prospect for mobile POS.

Cotton stalks (CS) are a potential agricultural biomass resource. We investigated the use of CS as a feed for Proteatia brevitarsis Lewis larvae and the resulting frass (larvae dung-sand) as a fertilizer. Based on a three-factor experiment (decomposition inoculant, fermentation duration, and cattle manure ratio), the optimal parameters for the transformation of CS using P. brevitarsis larvae were determined as 40–50% of cattle manure, the use of VT inoculant and a fermentation duration of 25–30 days. Regarding the products of the transformation, the protein content of the larval body was as high as 52.49%, and the fat content was 11.7%, which is a suitable-quality insect protein source. The organic matter content of larvae dung-sand was 54.8%, and the content of total nitrogen, phosphorus, and potassium (TNPK) was 9.04%, which is twice more than that of the organic fertilizer standard (NY525-2021, Beijing, China, TNPK ≥ 4.0%), and larvae dung-sand has the potential of fertilizer application. Therefore, CS as a feed and fertilizer based on the transformation of P. brevitarsis larvae is feasible, and it is a highly efficient way to promote the utilization of both CS and cattle manure.

Arable land ecosystems are among the most important terrestrial systems. The issues of carbon sequestration and emission reductions in arable land ecosystems have received extensive attention. Countries around the world have actively issued policies to manage arable land ecosystems. At present, more than 100 countries have made carbon neutralization target commitments. Various arable land management measures and arable land planting strategies have important impacts on the carbon storage of arable land ecosystems. Research on arable land carbon is of great significance to global climate change. This study attempts to investigate the problems and deficiencies in the current research by summarizing a number of studies, including the main methods for the quantitative research of carbon sources and sinks as well as the influencing factors in these ecosystems. In this study, it is found that due to the differences of climate patterns, soil properties and management practices in arable land ecosystems, the factors affecting carbon sources and sinks are of great heterogeneity and complexity. Generally, variations in natural factors affect the carbon balance in different regions, while human management measures, such as irrigation, fertilization and the degree of agricultural mechanization, are the leading factors causing changes to carbon sources and sinks in these ecosystems. In addition, there are still great uncertainties in the evaluation of carbon sources and sinks in these ecosystems caused by different estimation models and methods. Therefore, emphasis should be placed on model parameter acquisition and method optimization in the future. This review provides a scientific basis for understanding carbon sources and sinks in arable land ecosystems, enhancing their carbon sink capacity and guiding low-carbon agriculture on arable land.

In this study, we attempt to analyze the influence of different excitation factors on the dynamic behavior of a gear transmission system in a braiding machine. In order to observe nonlinear characteristics, a mathematical model is established with a six-degrees-of-freedom gear system for consideration of multiple excitation factors. Iterative results are used to study the nonlinear characteristics of the gear system with respect to contact temperature, varying levels of friction, and disturbance of yarn tension using bifurcation diagrams, maximum Lyapunov exponents, phase diagrams, Poincare maps, and the power spectrum. The numerical results show that excitation factors such as temperature and surface friction, among others, have considerable influence on the nonlinear characteristics of the gear system in a braiding machine, and the model is evaluated to show the key regions of sensitivity. The analysis of associated parameters can be helpful in the design and control of braiding machines.

Aiming at the particularity of a multiple-stage closed-loop gear transmission system for 3D circular braiding machine, the model of gear transmission system in radial braiding machine was simplified. The non-linear dynamic equations of a n-elements closed-loop gear transmission system with symmetrical structure including static transmission error, the random disturbance of meshing damping and backlash were considered. For convenience of calculation n = 3, the equations were solved numerically by using Runge-Kutta. The dynamic transmission error(DTE) with different backlash, dynamic meshing forces with and without the random disturbance of meshing damping, the amplitude of dynamic transmission error at n = 1000 r/min and b = 2.65 × 10−5 m, root mean square(RMS) of DTE and the mean value of DTE of the first pair of gears were analyzed. The simulation results show that different backlash and the random disturbance of meshing damping have a great influence on the dynamic displacement error and meshing force of the gear pair, and RMS and the mean value of DTE changes at different rotational speeds. The results will provide a reference for realizing the smoothness of the closed-loop gear transmission system with symmetrical structure for 3D braiding machine and have great practical significance for improving the braiding quality.

Since neutralizing antibodies (NAb) targeting the human cytomegalovirus (HCMV) pentamer complex (PC) potently block HCMV host cell entry, anti-PC NAb induction is thought to be important for a vaccine formulation to prevent HCMV infection. By developing a vaccine strategy based on soluble PC protein and using a previously generated Modified Vaccinia Ankara vector co-expressing all five PC subunits (MVA-PC), we compared HCMV NAb induction by homologous immunization using prime-boost vaccine regimen employing only PC protein or MVA-PC and heterologous immunization using prime-boost combinations of PC protein and MVA-PC. Utilizing a recently isolated anti-PC NAb, we produced highly pure soluble PC protein that displayed conformational and linear neutralizing epitopes, interfered with HCMV entry, and was recognized by antibodies induced by HCMV during natural infection. Mice vaccinated by different immunization routes with the purified PC protein in combination with a clinically approved adjuvant formulation elicited high-titer and durable HCMV NAb. While MVA-PC and soluble PC protein either alone or in combination elicited robust HCMV NAb, significantly different potencies of these vaccine approaches were observed in dependence on immunization schedule. Using only two immunizations, vaccination with MVA-PC alone or prime-boost combinations of MVA-PC and PC protein was significantly more effective in stimulating HCMV NAb than immunization with PC protein alone. In contrast, with three immunizations, NAb induced by soluble PC protein either alone or combined with two boosts of MVA-PC increased to levels that exceeded NAb titer stimulated by MVA-PC alone. These results provide insights into the potency of soluble protein and MVA to elicit NAb by the HCMV PC via homologous and heterologous prime-boost immunization, which may contribute to develop clinically deployable vaccine strategies to prevent HCMV infection.

UnlabelledHuman cytomegalovirus (HCMV) elicits neutralizing antibodies (NAb) of various potencies and cell type specificities to prevent HCMV entry into fibroblasts (FB) and epithelial/endothelial cells (EpC/EnC). NAb targeting the major essential envelope glycoprotein complexes gB and gH/gL inhibit both FB and EpC/EnC entry. In contrast to FB infection, HCMV entry into EpC/EnC is additionally blocked by extremely potent NAb to conformational epitopes of the gH/gL/UL128/130/131A pentamer complex (PC). We recently developed a vaccine concept based on coexpression of all five PC subunits by a single modified vaccinia virus Ankara (MVA) vector, termed MVA-PC. Vaccination of mice and rhesus macaques with MVA-PC resulted in a high titer and sustained NAb that blocked EpC/EnC infection and lower-titer NAb that inhibited FB entry. However, antibody function responsible for the neutralizing activity induced by the MVA-PC vaccine is uncharacterized. Here, we demonstrate that MVA-PC elicits NAb with cell type-specific neutralization potency and antigen recognition pattern similar to human NAb targeting conformational and linear epitopes of the UL128/130/131A subunits or gH. In addition, we show that the vaccine-derived PC-specific NAb are significantly more potent than the anti-gH NAb to prevent HCMV spread in EpC and infection of human placental cytotrophoblasts, cell types thought to be of critical importance for HCMV transmission to the fetus. These findings further validate MVA-PC as a clinical vaccine candidate to elicit NAb that resembles those induced during HCMV infection and provide valuable insights into the potency of PC-specific NAb to interfere with HCMV cell-associated spread and infection of key placental cells.ImportanceAs a consequence of the leading role of human cytomegalovirus (HCMV) in causing permanent birth defects, developing a vaccine against HCMV has been assigned a major public health priority. We have recently introduced a vaccine strategy based on a widely used, safe, and well-characterized poxvirus vector platform to elicit potent and durable neutralizing antibody (NAb) responses targeting the HCMV envelope pentamer complex (PC), which has been suggested as a critical component for a vaccine to prevent congenital HCMV infection. With this work, we confirm that the NAb elicited by the vaccine vector have properties that are similar to those of human NAb isolated from individuals chronically infected with HCMV. In addition, we show that PC-specific NAb have potent ability to prevent infection of key placental cells that HCMV utilizes to cross the fetal-maternal interface, suggesting that NAb targeting the PC may be essential to prevent HCMV vertical transmission.

The proposition that "xungu tong yili" (an exegetical tradition leading to Confucian teachings) expresses the core idea of traditional Chinese philology, which threads throughout the Han and Song dynasties and reached its historical acme in the form of the Qian-Jia school. The overemphasis of scholars from this school on exegesis led to the division between Hanxue (Qing scholarship in the Han dynasty tradition) and Songxue (Qing scholarship in the Song dynasty tradition) and a disconnection between "xungu (Chinese exegetical tradition exegesis) and yili (Confucian teachings)." The modern "linguistized" shift has seen the slow death of the xunguxue tradition (the theory and practice of xungu as a discipline), under which "xungu tong yili." At the same time, modern xunguxue has clarified its own disciplinary orientation and has made great progress in both theory and practice, laying a reliable foundation for the renewed process of working out meanings through xungu. The heights of modern xunguxue allow the scholarly development of the meanings behind the classic texts in five respects: semantic verification, context representation, validation of themes, history of xungu interpretation, and pursuit of imagery. In the cross-disciplinary collision centered on Chinese hermeneutics, the modern approach to the proposition that "xungu tong yili" has shown abundant vitality. [ABSTRACT FROM AUTHOR]