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Abstract Bacterial RNAP needs to form holoenzyme with σ factors to initiate transcription. While Staphylococcus aureus σA controls housekeeping functions, S. aureus σB regulates virulence, biofilm formation, persistence, cell internalization, membrane transport, and antimicrobial resistance. Besides the sequence difference, the spacers between the −35 element and −10 element of σB regulated promoters are shorter than those of σA regulated promoters. Therefore, how σB recognizes and initiates transcription from target promoters can not be inferred from that of the well studied σ. Here, we report the cryo-EM structures of S. aureus RNAP-promoter open complexes comprising σA and σB, respectively. Structural analyses, in combination with biochemical experiments, reveal the structural basis for the promoter specificity of S. aureus transcription. Although the −10 element of σA regulated promoters is recognized by domain σA 2 as single-stranded DNA, the −10 element of σB regulated promoters is co-recognized by domains σB 2 and σB 3 as double-stranded DNA, accounting for the short spacers of σB regulated promoters. S. aureus RNAP is a validated target of antibiotics, and our structures pave the way for rational drug design targeting S. aureus RNAP.

Biogenic volatile organic compounds (BVOCs) are responsible for the formation of ozone and secondary organic aerosols (SOAs). Our knowledge about how black carbon particles influence BVOC emissions from terrestrial ecosystems is limited; terrestrial vegetation captures black carbon particles as a sink. In this research, the BVOC emissions from the leaves of four terrestrial plants were measured using an RAE PGM-7300 BVOC analyzer. Then, the leaves from four types of trees were exposed to submicron carbon black for 24 h and 48 h in an ambient environment, respectively. Comparisons between the BVOC emissions before and after exposure to submicron carbon black were performed. Our results indicated that the emissions of BVOC from the leaves of four types of trees varied from 90 to 270 μg g−1 h−1 and depended on the species. The exposure to submicron black carbon particles had negligible impacts on the BVOC emissions from the leaves of four types of trees.

A new unimodal distribution family indexed via the mode and three other parameters is derived from a mixture of a Gumbel distribution for the maximum and a Gumbel distribution for the minimum. Properties of the proposed distribution are explored, including model identifiability and flexibility in capturing heavy-tailed data that exhibit different directions of skewness over a wide range. Both frequentist and Bayesian methods are developed to infer parameters in the new distribution. Simulation studies are conducted to demonstrate satisfactory performance of both methods. By fitting the proposed model to simulated data and data from an application in hydrology, it is shown that the proposed flexible distribution is especially suitable for data containing extreme values in either direction, with the mode being a location parameter of interest. Using the proposed unimodal distribution, one can easily formulate a regression model concerning the mode of a response given covariates. We apply this model to data from an application in criminology to reveal interesting data features that are obscured by outliers.

Pembrolizumab and other immunotherapies have become central in treating metastatic colon cancer, particularly effective in patients with mismatch repair deficiencies. We report a case involving a man who initially underwent radical surgery for sigmoid colon cancer on April 27, 2011, followed by hepatic tumor resection on September 21, 2017. Post-surgery, he received eight cycles of adjuvant chemotherapy with the CAPEOX regimen and was regularly monitored through CT and MRI scans. On August 24, 2022, liver metastases were detected, and he was diagnosed with Lynch syndrome (LS) due to germline mutation in the MSH2 and EPCAM genes. He commenced treatment with 200mg of pembrolizumab intravenously every three weeks on September 2, 2022, and demonstrated a sustained response. However, after 17 cycles, he developed a treatment related adverse event (TRAE) of pancreatic endocrine dysfunction, leading to type 1 diabetes, managed with subcutaneous insulin injections. After 30 cycles of treatment, no evidence of disease was observed. This case underscores the significant clinical benefits of first-line pembrolizumab in managing hepatic metastasis in colonic carcinoma associated with LS, despite the occurrence of TRAEs. It raises critical questions regarding the optimal duration of immunotherapy following a complete or partial response and whether treatment should be discontinued upon the emergency of TRAEs. Continued research and forthcoming clinical trials with checkpoint inhibitors are expected to refine treatment protocols for LS-associated carcinoma.

Background: Traditional dose selection for oncology registration trials typically employs a one- or two-step single maximum tolerated dose (MTD) approach. However, this approach may not be appropriate for molecularly targeted therapy, which tends to have toxicity profiles that are markedly different than cytotoxic agents. The US Food and Drug Administration launched Project Optimus to reform dose optimization in oncology drug development and has recently released a related guidance for industry. Methods: We propose a “three steps toward dose optimization” procedure, in response to these initiatives, and discuss the details in dose-optimization designs and analyses. The first step is dose escalation to identify the MTD or maximum administered dose with an efficient hybrid design, which can offer good overdose control and increases the likelihood of the recommended MTD being close to the true MTD. The second step is the selection of appropriate recommended doses for expansion (RDEs), based on all available data, including emerging safety, pharmacokinetics, pharmacodynamics, and other biomarker information. The third step is dose optimization, which uses data from a randomized fractional factorial design with multiple RDEs explored in multiple tumor cohorts during the expansion phase to ensure a feasible dose is selected for registration trials, and that the tumor type most sensitive to the investigative treatment is identified. Conclusion: We believe using this three-step approach can increase the likelihood of selecting an optimal dose for a registration trial that demonstrates a balanced safety profile while retaining much of the efficacy observed at the MTD.

In our previous study, the ultrasound-assisted enzymatic extract of Platanus acerifolia leaves (PAL) was confirmed as an efficient corrosion inhibitor of steel. In this study, a new strategy-ultrafiltration-was proposed to further enhance the corrosion inhibition effect of this green steel corrosion inhibitor. To pinpoint the main players in the corrosion-inhibiting performance, the active compounds of the treated PAL extract were further quantitatively characterized via high performance liquid chromatography (HPLC). Electrochemical approaches were employed to investigate the anti-corrosion behavior. The adsorption film and surface morphology of the steel surface were characterized via X-ray photoelectron spectroscopy (XPS) and scanning electron microscope with energy dispersive spectrometer (SEM-EDS), respectively. Furthermore, simulations were carried out to further explore the inhibition mechanisms of the active molecules. The results showed that ultrafiltration significantly removed the polysaccharide impurities, thereby further concentrating the inhibition constituents. Twelve flavonoids and their derivatives were quantitatively traced, among which the procyanidins was the most pronounced ingredient (220 ppm). Ultrafiltration can effectively improve the inhibition performance of the extract. In the presence of chloride ions, the inhibition efficiency of the 1.5 wt% two-step processed extract was equivalent to that of the 5 wt% primary extract. Plus, SEM-EDS observations confirmed that the two-step processed extract was able to effectively mitigate the corrosion degree. XPS and simulation analyses revealed that the flavonoids and their derivatives executed the corrosion inhibition performance by forming a protective carbon-containing organic film on the steel surface via chelation and surface physical adsorption.

Abstract Purpose Lung cancer has a high morbidity and mortality rate of all cancers worldwide. Therefore, there is an urgent need for reliable cancer markers for diagnosis and prognosis of patients with lung cancer. Methods In this study, we used the bioinformatics database to compare the expression of the TBX2 subfamily at the transcriptional and protein levels in non-small cell lung cancer. Then, to confirm our bioinformatics analysis above, we used western bloting to determine the expression of TBX2, TBX3, TBX4 and TBX5 in human lung squamous carcinoma cell lines. Besides, low expression of TBX2 subfamily predicted a poor prognosis of patients with lung cancer. Finally, The methylation database was used to explore the relationship between the low expression of TBX2 subfamily and methylation of gene promoter region. Results Our data showed a significant decrease of TBX2 subfamily expression in lung cancer tissues of several histological subtypes. Finally, the methylation of TBX2 subfamily members in the promoter region of NSCLC was significantly higher than that in normal tissues. Conclusion Our research provided sufficient evidence that TBX2 subfamily might play an inhibitory role in malignancy progression of lung cancer, which is promising to shed light on discovering a novel reliable cancer marker for prognosis of lung cancer patients.

Lattice structures, one type of mechanical metamaterials, exhibit excellent mechanical properties such as a high strength-to-weight ratio and energy absorption capacity. However, predicting the stress–strain relationship of lattice structures remains a challenge because the mechanical behaviors of additively manufactured lattices are affected by both the structure parameters of a lattice and process conditions. This study proposes a machine learning (ML)-based predictive modeling framework to predict the entire stress–strain curves, compressive modulus, and energy absorption of lattice structures with varying structure and process parameters. Feature engineering techniques are used to transform raw data into new data representations compatible with ML models, including artificial neural networks, long short-term memory (LSTM), and convolutional neural networks (CNN). Two novel feature representations, including polygons and colormaps, are developed to transform structure and process parameters from tabular format into image format for CNN. The LSTM model that predicts stress–strain curves achieves a minimum mean absolute percentage error (MAPE) of 0.147. The CNN (colormap) model achieves a minimum MAPE of 0.174 when predicting compressive modulus. The ANN and LSTM models achieve a minimum MAPE of 0.068 when predicting energy absorption. The training time to build these ML models is less than 6 min.

Summary: Innate lymphoid cells (ILCs), strategically positioned throughout the body, undergo population declines over time. A solution to counteract this problem is timely mobilization of multipotential progenitors from the bone marrow. It remains unknown what triggers the mobilization of bone marrow ILC progenitors (ILCPs). We report that ILCPs are regulated by the circadian clock to emigrate and generate mature ILCs in the periphery. We found that circadian-clock-defective ILCPs fail to normally emigrate and generate ILCs. We identified circadian-clock-controlled endocrine and cytokine cues that, respectively, regulate the retention and emigration of ILCPs at distinct times of each day. Activation of the stress-hormone-sensing glucocorticoid receptor upregulates CXCR4 on ILCPs for their retention in the bone marrow, while the interleukin-18 (IL-18) and RORα signals upregulate S1PR1 on ILCPs for their mobilization to the periphery. Our findings establish important roles of circadian signals for the homeostatic efflux of bone marrow (BM) ILCPs.

The United Nations proposed the Sustainable Development Goals with the aim to make human settlements in cities resilient and sustainable. The excessive discharge of urban waste including sludge and garden waste can pollute groundwater and lead to the emission of greenhouse gases (e.g., CH4). The proper recycling of urban waste is essential for responsible consumption and production, reducing environmental pollution and addressing climate change issues. This study aimed to prepare biochar with high adsorption amounts of iodine using urban sludge and peach wood from garden waste. The study was conducted to examine the variations in the mass ratio between urban sludge and peach wood (2/1, 1/1, and 1/2) as well as pyrolysis temperatures (300 °C, 500 °C, and 700 °C) on the carbon yield and adsorption capacities of biochar. Scanning electron microscopy, Brunauer–Emmett–Teller analysis, Fourier transform infrared spectrometry, powder X-ray diffraction, and elemental analysis were used to characterize the biochar produced at different pyrolysis temperatures and mass ratios. The results indicate that the carbon yield of biochar was found to be the highest (>60%) at a pyrolysis temperature of 300 °C across different pyrolysis temperatures. The absorbed amounts of iodine in the aqueous solution ranged from 86 to 223 mg g−1 at a mass ratio of 1:1 between urban sludge and peach wood, which were comparably higher than those observed in other mass ratios. This study advances water treatment by offering a cost-effective method by using biochar derived from the processing of urban sludge and garden waste.

Ventilation may lead to a deterioration in indoor air quality in urban environments located close to roads. Understanding the differences in the chemical compositions of size-resolved particulate matter (PM) in indoor air and outdoor air could aid in assessing the health impacts of air in these settings and establishing relevant regulation policies. In this study, indoor and outdoor size-resolved PM was collected from an office in Beijing in summer (between 5 and 25 July 2020) and winter (between 5 and 31 January 2021). Its chemical components, including sulfate, nitrate, ammonium, chlorine, organic matter (OM), elemental carbon (EC), crustal materials (CM), and heavy metals (HM), were analyzed. The mean levels of indoor and outdoor PM2.1 and PM9 were found to be much higher than those in the guidelines for PM2.5 and PM10 outlined by the National Ambient Air Quality Standard. Moreover, the levels of PM2.1 and PM2.1–9 mass were higher outdoors than they were indoors. The size distributions of mass concentrations were shown to be bimodal, peaking at 0.43–0.65 μm and 4.7–5.8 μm, respectively. The most abundant chemicals were OM, nitrate, and sulfate for PM2.1 and OM, CM, and nitrate for PM2.1–9. We found higher percentages of sulfate, nitrate, ammonium, EC, and HM in smaller-size fractions of PM. Additionally, positive matrix factorization showed that biomass burning, secondary inorganic aerosol, coal combustion, dust, traffic, and industrial pollution were the main sources of PM during the study period. The greatest non-carcinogenic and carcinogenic hazards were found at 0.43–0.65 μm in summer and 2.1–3.3 μm in winter. Our results indicate that size-resolved PM of ambient origin may infiltrate buildings near roads to varying degrees, resulting in negative health effects.

With the development of lightweight engineering, load-bearing structures such as synthetic fiber ropes are being increasingly used in engineering projects. During the process of repeated stretching or bending, abrasion occurs between the yarns of fiber assemblies like ropes. Fatigue failure caused by abrasion between yarns is one of the main reasons for the failure of such fiber assemblies. Different chain segments of fiber assemblies exhibit different properties. This study takes the four fibers of flexible chain fibers Ultra-high molecular weight polyethylene (UHMWPE), Polyethylene glycol terephthalate (PET) and rigid chain fibers Poly-p-phenylene terephthamide (PPTA) and Polyarylate (PAR), which are widely used in ropes and cables, as the research materials, and explores the influence of abrasion frequency and yarn tension on different chain segment fibers. To explore the failure and influencing factors of rigid chain and flexible chain fibers abrasion leads to fiber assemblies like those ropes. Based on the observation and analysis of the abrasion zone temperature, yarn state, and wear debris morphology of failed yarns, an abrasion failure mechanism is proposed, providing guidance for the design and application of fatigue-resistant products for ropes.

Microwaves have the advantage of penetrating vegetation and exhibit sensitivity to properties such as vegetation water content (VWC); yet, their potential utility in the fire domain is infrequently investigated. This study elucidates the different impacts of the microwave VWC index EDVI on fire radiative energy (FRE) across various biome types and the significant predictive power for high-severity fires (defined based on FRE) in mainland Southeast Asia. While EDVI exhibits lower predictive power for high severe fires compared to the commonly used fire weather indices (e.g., FWI), an enhancement is observed when these predictors are used in combination. Either by employing EDVI or fire weather indices, the predictability of fires is found to be highest over forests and lowest over croplands. Factors such as increasing human influence and fuel limitation in croplands are likely reducing the roles of VWC and weather on fires, contributing to the lower prediction skill of EDVI and fire weather. These results indicate the usefulness of microwave VWC index in fire studies. Although fire weather presents more considerable impacts on fires, the microwave VWC index seem to still provide some complementary information in fire danger assessment.

ObjectivesVeteran parents experiencing posttraumatic stress disorder (PTSD) may resort to harsh parenting. The indirect pathway from parental military-related PTSD to harsh parenting, and the moderating role of parents' pre-military trauma histories, has been less explored. Informed by mentalization theory, as well as trauma-sensitive and posttraumatic growth perspectives, we aim to explore the associations between veteran parents' military-related PTSD, mentalization, harsh parenting, and prior trauma before military service.MethodsData were collected from an online research panel of 509 veteran parents with children under 10. We employed Structural Equation Models to test indirect and moderating effects.ResultsWe identified an indirect effect of parental pre-mentalization from military PTSD to harsh parenting [corporal punishment: b = 0.35, p < 0.001, 95% CI (0.23, 0.46); psychological aggression: b = 0.14, p < 0.001, 95% CI (0.09, 0.19)]. Multi-group analysis on four parent groups (parents with only pre-military physical trauma, parents with only pre-military psychological trauma, parents with both pre-military physical and psychological trauma, and parents with no pre-military physical or psychological trauma) highlighted differences in these associations, particularly between parents with only pre-military physical trauma and those without any physical and psychological trauma. The military-related PTSD effects on psychological aggression, corporal punishment, and pre-mentalization were all significantly higher for parents without pre-military physical and psychological trauma.ConclusionModifying parents' interpretation of their child's mental states can potentially counteract the effects of veterans' military PTSD on harsh parenting. Family-based programs should be created considering veteran parents' pre-military trauma histories.

In order to provide insights into how various page views are influenced by public engagement with weather information and to shed light on the patterns of warning issuance across different seasons and regions, this study analyzes the multi-dimensional characteristics of city weather forecast page views and the spatiotemporal characteristics of early warning information in China, from 1 March 2020 to 31 August 2023. This is achieved by utilizing the daily page views of city weather forecasts and meteorological warning data, comparing the public’s attention to weather during holidays versus regular days, assessing the public’s attention to weather under different meteorological warning levels, and performing statistical analysis of the spatiotemporal scale of meteorological disasters. Our analysis shows that compared to weekends and holidays, the public pays more attention to the weather on weekdays, and the difference between weekdays and national statutory holidays is more significant. Due to the widespread impact of heat waves, typhoons, severe convective weather, and geological disasters caused by heavy rainfall, public awareness and participation in flood season weather forecasting have significantly increased. Under red alerts, flash floods, typhoons, and geological risks are the primary concerns. Orange alerts predominantly feature flash floods, rainstorms, typhoons, snowstorms, and cold waves, while sandstorms attract the most attention during yellow alerts. Droughts, however, receive relatively less attention regardless of the warning level. Seasonal patterns in the issuance of meteorological warnings reveal a peak in summer, particularly with typhoons and rainstorms being the main concerns in July, followed by high temperatures and additional typhoon warnings in August. Heavy sea surface wind warnings exhibit a strong seasonal trend, with the majority issued during the winter months. Regionally, southern China experiences the highest frequency of severe convection weather warnings, with provinces such as Jiangxi, Guangxi, and Hunan being the most affected.

To address the challenges associated with wind power integration, this paper analyzes the impact of distributed renewable energy on the voltage of the distribution network. Taking into account the fast control of photovoltaic inverters and the unique characteristics of photovoltaic arrays, we establish an active distribution network voltage reactive power-optimization model for planning the active distribution network. The model involves solving the original non-convex and non-linear power-flow-optimization problem. By introducing the second-order cone relaxation algorithm, we transform the model into a second-order cone programming model, making it easier to solve and yielding good results. The optimized parameters are then applied to the IEEE 33-node distribution system, where the phase angle of the node voltage is adjusted to optimize the reactive power of the entire power system, thereby demonstrating the effectiveness of utilizing a second-order cone programming algorithm for reactive power optimization in a comprehensive manner. Subsequently, active distribution network power quality control is implemented, resulting in a reduction in network loss from 0.41 MW to 0.02 MW. This reduces power loss rates, increases utilization efficiency by approximately 94%, optimizes power quality management, and ensures that users receive high-quality electrical energy.

The polycyclic aromatic hydrocarbons (PAHs) in size-resolved particles emitted from diverse sources are required for quantification to reduce the emissions in order to protect public health. Twenty-four PAHs in size-segregated particles in the roadside environment of Beijing were observed from 1 October 2021 to 30 September 2022. The size distributions of PAHs were bimodal, with peak concentrations ranging from size fractions of 0.43 to 0.65 μm and 4.7 to 5.8 μm in all four seasons, respectively. The highest concentration of PAHs in fine particles (PM2.1) was 35.3 ng m−3 in winter, followed by 16.0 ng m−3 in autumn, 15.3 ng m−3 in spring, and 6.5 ng m−3 in summer. Conversely, the concentration of PAHs in coarse particles (PM2.1–9) ranged from 6.8 ng m−3 (summer) to 20.5 ng m−3 (winter) from low to high. The size fractions of 0.43–2.1 μm PAHs increased most from clear to polluted days, which could be ascribed to the heterogeneous reactions. Source apportionment using positive matrix factorization showed that four sources, namely biomass combustion, coal combustion, diesel vehicles, and gasoline vehicles accounted for PAHs with the estimation of 17.4%, 22.1%, 26.4%, and 23.2% to PAHs in PM2.1; and 19.6%, 24.3%, 23.6%, and 20.1% in PM2.1–9, respectively. Furthermore, we used the human alveolar epithelial cell (BEAS-2B) to assess the toxicological effects of size-resolved atmospheric PAHs. The results showed that the cell survival rate caused by fine particles was lower than that of coarse particles with the same concentrations of PAHs, which is mainly related to the higher content of highly toxic PAHs in fine particles.

The overall oocyte quality declines with aging, and this effect is strongly associated with a higher reactive oxygen species (ROS) level and the resultant oxidative damage. C-type natriuretic peptide (CNP) is a well-characterized physiological meiotic inhibitor that has been successfully used to improve immature oocyte quality during in vitro maturation. However, the underlying roles of CNP in maternally aged oocytes have not been reported. Here, we found that the age-related reduction in the serum CNP concentration was highly correlated with decreased oocyte quality. Treatment with exogenous CNP promoted follicle growth and ovulation in aged mice and enhanced meiotic competency and fertilization ability. Interestingly, the cytoplasmic maturation of aged oocytes was thoroughly improved by CNP treatment, as assessed by spindle/chromosome morphology and redistribution of organelles (mitochondria, the endoplasmic reticulum, cortical granules, and the Golgi apparatus). CNP treatment also ameliorated DNA damage and apoptosis caused by ROS accumulation in aged oocytes. Importantly, oocyte RNA-seq revealed that the beneficial effect of CNP on aged oocytes was mediated by restoration of mitochondrial oxidative phosphorylation, eliminating excessive mitophagy. CNP reversed the defective phenotypes in aged oocytes by alleviating oxidative damage and suppressing excessive PINK1/Parkin-mediated mitophagy. Mechanistically, CNP functioned as a cAMP/PKA pathway modulator to decrease PINK1 stability and inhibit Parkin recruitment. In summary, our results demonstrated that CNP supplementation constitutes an alternative therapeutic approach for advanced maternal age-related oocyte deterioration and may improve the overall success rates of clinically assisted reproduction in older women.

ObjectiveTo promote the development and therapeutic application of new medications, it is crucial to conduct a thorough investigation into the mechanism by which the traditional Chinese herb pair of Haizao-Kunbu (HK) treats Graves’ disease (GD).Materials and methodsChemical ingredients of HK, putative target genes, and GD-associated genes were retrieved from online public databases. Using Cytoscape 3.9.1, a compound-gene target network was established to explore the association between prosperous ingredients and targets. STRING, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathway analyses visualized core targets and disease pathways. Additionally, we conducted a refined analysis of the binding interactions between active ingredients and their respective targets. To visualize these findings, we employed precise molecular docking techniques. Furthermore, we carried out molecular dynamics simulations to gain insights into the formation of more tightly bound complexes.ResultsWe found that there were nine key active ingredients in HK, which mainly acted on 21 targets. These targets primarily regulated several biological processes such as cell population proliferation, protein phosphorylation, and regulation of kinase activity, and acted on PI3K-AKT and MAPK pathways to treat GD. Analysis of the molecular interaction simulation under computer technology revealed that the key targets exhibited strong binding activity to active ingredients, and Fucosterol-AKT1 and Isofucosterol-AKT1 complexes were highly stable in humans.ConclusionThis study demonstrates that HK exerts therapeutic effects on GD in a multi-component, multi-target, and multi-pathway manner by regulating cell proliferation, differentiation, inflammation, and immunomodulatory-related targets. This study provides a theoretical foundation for further investigation into GD.

The financial condition of an enterprise is a critical factor in determining its viability and long-term prospects, and it also directly affects the interests of stakeholders such as investors and creditors. So extra attention is needed to evaluate and forecast the financial risk of an enterprise. This paper proposes a novel enterprise financial risk evaluation and prediction model integrating Synthetic Minority Over-sampling and Edited Nearest Neighbors (SMOTE-ENN) and Natural Gradient Boosting (NGBoost). The CRITIC-TOPSIS method is first employed to conduct a comprehensive evaluation of the financial risk of the listed companies based on their annual financial statements. Subsequently, the obtained evaluation results are subjected to a clustering analysis to categorize the companies into different levels of financial risk. To address the issue of imbalanced samples, the study introduces the SMOTE-ENN combined sampling method. This technique is applied to mitigate the imbalance in the number of samples across different categories. Lastly, NGBoost is utilized to develop a prediction model for corporate financial risk based on the clustered data. The analysis reveals that companies with low levels of financial risk typically exhibit a balanced financial profile, robust operational performance, and substantial growth potential. Conversely, companies with high levels of financial risk are characterized by weak profitability and debt-paying ability. The experimental findings show that the model has a 97.18% accuracy rate, thereby suggesting that the model is both reasonable and practicable.

Abstract Background Rheumatoid arthritis (RA) is an autoimmune disease characterized by destructive and symmetrical joint diseases and synovitis. This research attempted to explore the mechanisms involving ferroptosis in RA, and find the biological markers by integrated analysis. Methods Gene expression data (GSE55235 and GSE55457) of synovial tissues from healthy and RA individuals were downloaded. By filtering the differentially expressed genes (DEGs) and intersecting them with the 484 ferroptosis-related genes (FRGs), the overlapping genes were identified. After the enrichment analysis, the machine learning-based approaches were introduced to screen the potential biomarkers, which were further validated in other two datasets (GSE77298 and GSE93272) and cell samples. Besides, we also analyze the infiltrating immune cells in RA and their correlation with the biomarkers. Results With the criteria, 635 DEGs in RA were included, and 29 of them overlapped in the reported 484 FRGs. The enrichments of the 29 differentially expressed ferroptosis-related genes indicated that they may involve in the FoxO signaling pathway and inherited metabolic disorder. RRM2, validating by the external datasets and western blot, were identified as the biomarker with the high diagnostic value, whose associated immune cells, such as Neutrophils and Macrophages M1, were also further evaluated. Conclusion We preliminary explored the mechanisms between ferroptosis and RA. These results may help us better comprehend the pathophysiological changes of RA in basic research, and provide new evidences for the clinical transformation.

There is a need for monitoring air pollution associated with black carbon (BC) using a passive monitor is required in remote areas where the measurements are absent. In this pilot study, we developed a quantitative method to determine dry deposition submicron BC using dual-wavelength ultraviolet–visible spectroscopy. Furthermore, we measured the levels of dry deposition BC on plant leaves from 30 plant species located in urban Nanjing using the established method. The oxidative potential of BC on plant leaves as passive bio-monitoring samplers was assessed. The concentrations of black carbon (BC) on tree leaves varied from 0.01 to 1.6 mg m−2. Significant differences in levels of BC across leaves from different tree types were observed. The values of oxidative potential in deposited particles of leaf samples were observed to be in the range of 33–46 nmol min−1 mg−1 using the dithiothreitol (DTT) assay and 18–32 nmol min−1 mg−1 using the ascorbic acid (AA) assay, respectively. In comparison, the oxidative potential of BC-dominated mass in water extracts of leaf samples was in the range of 5–35 nmol min−1 mg−1 measured using the DTT assay and 2 to 12 nmol min−1 mg−1 using the AA assay, respectively. We found variations in the levels of OP across the leaves of different tree types were not large, while the levels of OP in terms of BC-dominated mass varied greatly. These results indicate that the established method with dual-wavelength ultraviolet–visible spectroscopy could provide a simple tool to determine submicron BC in plant leaves of the passive monitor.

With the continuous utilization of renewable energy, the number of onshore wind turbines is increasing. Small design improvements can save costs and facilitate the maintenance and repair of the wind turbine foundation. In this paper, an existing gravity expansion foundation with an anchor cage is improved. Our improvements further expand the space inside the foundation and reduce the length of the anchor bolt, which could reduce the costs and facilitate construction. To study the performance of the new foundation, a three-dimensional finite element model of the foundation–soil–anchor bolt was established via a finite element simulation. The damage evolution of the foundation was simulated with the concrete damage plasticity model (CDP). The separation ratio, foundation settlement, inclination ratio, reinforcement stress, foundation stress, and foundation damage of the new foundation under ultimate load conditions were analyzed. The influence of parameters h1 and b3 on the performance of the foundation was further studied. The finite element analysis results show that the tensile stress of concrete can be effectively reduced by appropriately increasing the corbel height and ring beam width of the foundation. The results also show that the improved wind turbine foundation force is reasonable and can meet the use of the actual project requirements on the level of finite element analysis.

Air pollution makes an impact on cardio-pulmonary health. Since people spend over 90% of their time indoors, exposures to the indoor environment make the most significant impact on health. Among indoor sources, cooking emits the most particles that disperse through the residential indoor environment and expose occupants. We use fully controlled simulated residential modules to conduct exposure experiments. In the pilot study, participants stayed in modules for 1 week, and in the main study, 14 participants will stay in the module for 4 weeks. One module is operated as a classical US house air supply recommendation. The second module has an advanced control system that, alongside the standard air supply, activates air quality interventions: stove hood, portable air cleaners, bathroom exhaust and air flush (increasing air supply ∼3 times) as a function of the PM2.5 levels in the space. Environmental sensors based on Internet of Things technology simultaneously monitored Particulate Matter (PM2.5), CO2, Total Volatile Organic Compounds Relative Humidity and air temperature in all spaces and operated air quality interventions. Participant’s scheduled activities include morning and evening tasks, Monday through Friday. Participants may leave the module during the day. They will be asked to cook breakfast and dinner using lab-provided recipes. We measured each participant’s blood pressure, heart rate, and heart rate variability. Blood and urine samples were collected 3 times per participant in the pilot and will be collected 2 times a week in the main study. Up to 20 ml of blood and a minimum of 30 ml of urine will be sampled per collection. Analysis of blood and urine was performed for 8-hydroxy-2-deoxyguanosine (8-OHdG, urine), von Willebrand Factor (vWF, blood plasma), high sensitivity C-Reactive Protein (hsCRP, blood serum), Interleukin-6 (blood plasma), CD11b (blood), Fibrinogen (blood plasma), and Myeloperoxidase (blood serum). We conducted a Pilot for 2 weeks with 3 participants to test the study protocol and data collection. We adjusted the protocol for the main study based on the pilot results. Results showed that the proposed study protocol could be completed, and the methodology adopted in this study will provide valuable insights into the relationship between exposure to cooking particles and occupants' health.Trial registration: Mayo Clinic IRB 20-007908.

Tardigrades, known colloquially as water bears or moss piglets, are diminutive animals capable of surviving many extreme environments, even been exposed to space in low Earth orbit. Recently termed tardigrade disordered proteins (TDPs) include three families as cytoplasmic-(CAHS), secreted-(SAHS), and mitochondrial-abundant heat soluble (MAHS) proteins. How these tiny animals survive these stresses has remained relatively mysterious. Cyanobacteria cast attention as a “microbial factory” to produce biofuels and high-value-added chemicals due to their ability to photosynthesis and CO2 sequestration. We explored a lot about biofuel stress and related mechanisms in Synechocystis sp. PCC 6803. The previous studies show that CAHS protein heterogenous expression in bacteria, yeast, and human cells increases desiccation tolerance in these hosts. In this study, the expression of three CAHS proteins in cyanobacterium was found to affect the tolerance to biofuels, while the tolerance to Cd2+ and Zn2+ were slightly affected in several mutants. A quantitative transcriptomics approach was applied to decipher response mechanisms at the transcriptional level further.

The leaves of plants can be recommended as a cheap and sustainable environmental protection tool to mitigate PAHs with high toxicity in the ambient environment because they can serve as a reactor to remove ambient PAHs. Although previous studies have demonstrated that PAHs exhibit toxicological features, our knowledge about how ambient PAHs influence the leaves of plants is limited regarding the leaves of plants reducing ambient PAHs as a reactor. In this study, 1-year-old Rosa chinensis Jacq. with good growth potential was selected as a model plant. The leaves of Rosa chinensis Jacq. were exposed to 16 types of PAHs in the environmental concentration exposure group (0.1 μg L−1) and high-concentration exposure group (5 μg L−1) for seven days. In comparison, the leaves of Rosa chinensis Jacq. were exposed to de-ionized water and were chosen as the control group. During the exposure periods, the physiological parameters of leaves including, chlorophyll value, water content, temperature and nitrogen, were monitored using a chlorophyll meter. After 7 days of exposure, the leaves in the control and exposure groups were collected and used for whole-transcriptome analysis. Our results demonstrate that significant differentially expressed genes were observed in the leaves of Rosa chinensis Jacq. exposed to individual PAHs at 5 μg L−1 compared to the control group. These differentially expressed genes were involved in seven main pathways using bioinformatic analyses. In contrast, the levels of PAHs at environmentally relevant concentrations had negligible impacts on the physiological parameters and the gene transcription levels of the leaves of Rosa chinensis Jacq. Our results may provide direct evidence to remove ambient PAHs using terrestrial trees without considering the risk of PAHs at environmentally relevant concentrations on the leaves of terrestrial plants.

Abstract Background Many studies on long chain non-coding RNAs (lncRNAs) are published in recent years. But the roles of lncRNAs in aortic dissection (AD) are still unclear and should be further examined. The present work focused on determining the molecular mechanisms underlying lncRNAs regulation in aortic dissection on the basis of the lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network. Methods This study collected the lncRNAs (GSE52093), mRNAs (GSE52093) and miRNAs (GSE92427) expression data within human tissue samples with aortic dissection group and normal group based on Gene Expression Omnibus (GEO) database. Results This study identified three differentially expressed lncRNAs (DELs), 19 differentially expressed miRNAs (DEmiRs) and 1046 differentially expressed mRNAs (DEGs) identified regarding aortic dissection. Furthermore, we constructed a lncRNA-miRNA-mRNA network through three lncRNAs (including two with up-regulation and one with down-regulation), five miRNAs (five with up-regulation), as well as 211 mRNAs (including 103 with up-regulation and 108 with down-regulation). Simultaneously, we conducted functional enrichment and pathway analyses on genes within the as-constructed ceRNA network. According to our PPI/ceRNA network and functional enrichment analysis results, four critical genes were found (E2F2, IGF1R, BDNF and PPP2R1B). In addition, E2F2 level was possibly modulated via lncRNA FAM87A-hsa-miR-31-5p/hsa-miR-7-5p or lncRNA C9orf106-hsa-miR-7-5p. The expression of IGF1R may be regulated by lncRNA FAM87A-hsa-miR-16-5p/hsa-miR-7-5p or lncRNA C9orf106-hsa-miR-7-5p. Conclusion In conclusion, the ceRNA interaction axis we identified is a potentially critical target for treating AD. Our results shed more lights on the possible pathogenic mechanism in AD using a lncRNA-associated ceRNA network.

ObjectiveMALT1 regulates immunity and inflammation in multiple ways, while its role in rheumatoid arthritis (RA) is obscure. This study aimed to investigate the relationship of MALT1 with disease features, treatment outcome, as well as its effect on Th1/2/17 cell differentiation and underlying molecule mechanism in RA.MethodsTotally 147 RA patients were enrolled. Then their blood Th1, Th2, and Th17 cells were detected by flow cytometry. Besides, PBMC MALT1 expression was detected before treatment (baseline), at week (W) 6, W12, and W24. PBMC MALT1 in 30 osteoarthritis patients and 30 health controls were also detected. Then, blood CD4+ T cells were isolated from RA patients, followed by MALT1 overexpression or knockdown lentivirus transfection and Th1/2/17 polarization assay. In addition, IMD 0354 (NF-κB antagonist) and SP600125 (JNK antagonist) were also added to treat CD4+ T cells.ResultsMALT1 was increased in RA patients compared to osteoarthritis patients and healthy controls. Meanwhile, MALT1 positively related to CRP, ESR, DAS28 score, Th17 cells, negatively linked with Th2 cells, but did not link with other features or Th1 cells in RA patients. Notably, MALT1 decreased longitudinally during treatment, whose decrement correlated with RA treatment outcome (treatment response, low disease activity, or disease remission). In addition, MALT1 overexpression promoted Th17 differentiation, inhibited Th2 differentiation, less affected Th1 differentiation, activated NF-κB and JNK pathways in RA CD4+ T cells; while MALT1 knockdown exhibited the opposite effect. Besides, IMD 0354 and SP600125 addition attenuated MALT1’s effect on Th2 and Th17 differentiation.ConclusionMALT1 regulates Th2 and Th17 differentiation via NF-κB and JNK pathways, as well as correlates with disease activity and treatment outcome in RA.

The engineering stress–strain curve of a material allows one to determine mechanical properties such as elastic modulus, strength, and toughness. While machine learning has recently been used to predict stress–strain curves, large volumes of experimental data are required to achieve high prediction accuracy. More importantly, conventional machine learning models are not generalizable from one material to another. To address this issue, a novel transfer learning approach is introduced to predict stress–strain curves across different fiber reinforced polymer (FRP) composites fabricated via additive manufacturing. Optimal transport (OT) is integrated with the transfer learning approach by mapping the source label space to the target label space, which further improves knowledge transferability across different FRP composites. The stress–strain curves of the additively manufactured FRP composites are generated under flexural loading conditions. Experimental results show that the OT-integrated transfer learning approach can predict the complex stress–strain curves of FRP composites with small training data. The predictive model achieved a mean absolute percentage error (MAPE) of less than 10%. The extracted modulus and strength from the predicted stress–strain curves achieved MAPEs of less than 5% and 10%, respectively. This work demonstrates that transfer learning has the potential to transform how stress–strain curves are generated.

Modern engineering applications require advanced materials that are stronger, tougher, and lighter. Nature offers various structural architectures to achieve superior mechanical properties. Inspired by bone with a spongy soft-core and a compact hard-shell, this study introduces architected multi-material lattices with tunable mechanical properties such as stiffness, strength, and energy absorption. The architected lattices are fabricated via multi-material fused filament fabrication. The hard polylactic acid (PLA) shell of the lattice struts maintains the stiffness, while the soft thermoplastic polyurethane (TPU) core enhances toughness and energy absorption capacity. The microstructural and mixed-mode fracture characteristics of the PLA-TPU interfaces were examined since the interfacial microstructure and adhesion are crucial to stress transfer in multi-phase composite materials. This study explores the flexural behavior of the multi-material struts and reveals two distinct failure modes depending on the volume fraction of the soft-core through 3-point bend tests. This study demonstrates the bio-inspired design on a hexagonal planar lattice with a strut thickness-to-length ratio of 0.3. Tunable stiffness, strength, and energy absorption are achieved by varying the core-to-strut thickness ratio. Compression test results show that the architected lattices exhibit an energy absorption capacity that is about 2–3 times greater than that of the constituent single-phase lattices.

Purpose: To development and validation of machine learning-based classifiers based on simple non-ocular metrics for detecting referable diabetic retinopathy (RDR) in a large-scale Chinese population–based survey.Methods: The 1,418 patients with diabetes mellitus from 8,952 rural residents screened in the population-based Dongguan Eye Study were used for model development and validation. Eight algorithms [extreme gradient boosting (XGBoost), random forest, naïve Bayes, k-nearest neighbor (KNN), AdaBoost, Light GBM, artificial neural network (ANN), and logistic regression] were used for modeling to detect RDR in individuals with diabetes. The area under the receiver operating characteristic curve (AUC) and their 95% confidential interval (95% CI) were estimated using five-fold cross-validation as well as an 80:20 ratio of training and validation.Results: The 10 most important features in machine learning models were duration of diabetes, HbA1c, systolic blood pressure, triglyceride, body mass index, serum creatine, age, educational level, duration of hypertension, and income level. Based on these top 10 variables, the XGBoost model achieved the best discriminative performance, with an AUC of 0.816 (95%CI: 0.812, 0.820). The AUCs for logistic regression, AdaBoost, naïve Bayes, and Random forest were 0.766 (95%CI: 0.756, 0.776), 0.754 (95%CI: 0.744, 0.764), 0.753 (95%CI: 0.743, 0.763), and 0.705 (95%CI: 0.697, 0.713), respectively.Conclusions: A machine learning–based classifier that used 10 easily obtained non-ocular variables was able to effectively detect RDR patients. The importance scores of the variables provide insight to prevent the occurrence of RDR. Screening RDR with machine learning provides a useful complementary tool for clinical practice in resource-poor areas with limited ophthalmic infrastructure.

Hot forging dies play an important role in metallurgy, automotive, aerospace and weapons industries. However, due to the high temperature and high pressure of hot forging die and the working environment of cyclic load, the friction and wear performance of hot forging die is poor and the service life is low. The use of traditional lubricants can prolong the life of the mold, but it will cause environmental pollution, harm to workers’ health and other problems. In this paper, 35Ni15Cr Fe-based self-lubricating die material was prepared by high energy ball milling and vacuum sintering. The wear properties of the materials were studied under ball-to-disc wear conditions at 600 °C. The results show that when CaF2 content is 8 wt%, the friction coefficient and wear rate of the material are the lowest, which are 0.3 and 0.9166 × 10−5 mm2 min−1, respectively. When the load increases, the friction coefficient first increases and then decreases, but the wear rate continues to increase. The wear mechanism mainly includes abrasive wear, adhesive wear, oxidation wear and fatigue wear. The friction reduction mechanism is that CaF2 is precipitated from the self-lubricating mold material and Fe and Ni are oxidized to the boss on the wear surface. The broken boss and lubricant form a lubricating film and accumulate into a glaze layer. The material can be used in high temperature forging environment without additional lubricant.

The method for the determination of 16 priority polycyclic aromatic hydrocarbons (PAHs) in plant leaves has been studied extensively, yet the quantitativemethod for measuring non-priority PAHs in plant leaves is limited. A method for the simultaneous determination of 31 polycyclic aromatic hydrocarbons (PAHs) in plant leaves was established using an ultrasonic extraction–gas chromatography–mass spectrometry–internal standard method. The samples of plant leaves were extracted with ultrasonic extraction and purified with solid-phase extraction columns. The PAHs were separated by using gas chromatography–mass spectrometry equipped with a DB-EUPAH capillary column (20 m × 0.18 mm × 0.14 μm) with a selective ion monitoring (SIM) detection mode, and quantified with an internal standard. The method had good linearity in the range of 0.005~1.0 μg/mL with correlation coefficients greater than 0.99, and the method detection limit and maximum quantitative detection limit were in the ranges of 0.2~0.7 μg/kg and 0.8~2.8 μg/kg, respectively. The method was verified with spiked recovery experiments. The average spiked recovery ranged from 71.0% to 97.6% and relative standard deviations (n = 6) were less than 14%. Herein, we established a quantitativemethod for the simultaneous determination of priority and non-priority PAHs in plant leaves using GC–MS. The method is highly sensitive and qualitatively accurate, and it is suitable for the determination of PAHs in plant leaves.

N6-methyladenosine (m6A) is the most abundant internal modification that widely participates in various immune and inflammatory responses; however, its regulatory mechanisms in the inflammation of liver induced by lipopolysaccharide in piglets remain largely unknown. In the present study, piglets were intraperitoneally injected with 80 μg/kg LPS or an equal dose of sterile saline. Results indicated that LPS administration increased activities of serum alanine aminotransferase (ALT), induced M1 macrophage polarization and promoted secretion of inflammatory cytokines, and finally led to hepatic lesions in piglets. The NOD1/NF-κB signaling pathway was activated in the livers of the LPS group. Moreover, the total m6A level was significantly elevated after LPS treatment. MeRIP-seq showed that 1166 and 1344 transcripts contained m6A methylation in control and LPS groups, respectively. The m6A methylation sites of these transcripts mainly distributes in the 5′ untranslated region (5′UTR), the coding sequence (CDS), and the 3′ untranslated region (3′UTR). Interestingly, these genes were mostly enriched in the NF-κB signaling pathway, and LPS treatment significantly changed the m6A modification in NOD1, RIPK2, NFKBIA, NFKBIB, and TNFAIP3 mRNAs. In addition, knockdown of METTL3 or overexpression of FTO both changed gene levels in the NOD1/NF-κB pathway, suggesting that activation of this pathway was regulated by m6A RNA methylation. Moreover, the alteration of m6A RNA methylation profile may be associated with the increase of reactive oxygen species (ROS), HIF-1α, and MAT2A. In conclusion, LPS activated the NOD1/NF-κB pathway at post-transcriptional regulation through changing m6A RNA methylation, and then promoted the overproduction of proinflammatory cytokines, ultimately resulting in liver inflammation and damage.

Cities around the Bohai Sea are one of the main population cluster areas in China, which are characterized by high levels of sustainability performance and human capital, as well as resource-intensive industries. In this study, levels of economic development metrics and emissions of air pollutants (BC, CO, NH3, NOx, OC, PM2.5, PM10, and SO2) and CO2 across eleven cities around the Bohai Sea from 2008 to 2017 were compared to illustrate the potential relationships between air pollutants/carbon emissions and socioeconomic developments. Meanwhile, the associations between the levels of economic development metrics (GDP per capita), emissions, and energy use per GDP have also been examined. Large differences across these 11 cities presenting different economic development levels and energy consumption characteristics have been observed. Cities with development dependable on the consumption of fossil fuels and the development of resource-intensive industries have emitted large amounts of air pollutants and CO2. Furthermore, the emissions and energy use per GDP for all the cities follow environmental Kuznets curves. The comparison results suggested that the developing cities dependable on resource-intensive industries around the Bohai Sea would obtain greater socioeconomic benefits owing to the interregional cooperation policies under top-down socioeconomic development plans and bottom-up technology development, accompanied by reduced emissions of air pollutants and CO2.

Undoubtedly, opioid drugs have been the most popular treatment for refractory pain since found, such as morphine. However, tolerance to the analgesic effects caused by repeated use is inevitable, which greatly limits the clinical application of these drugs. Nowadays, it has become the focus of the world that further development of non-opioid-based treatment along with efficient strategies to circumvent opioid tolerance are urgently needed clinically. Fortunately, electro-acupuncture (EA) provides an alternative to pharmaceutic treatment, remaining its potential mechanisms unclear although. This study was aimed to observe the effects of EA on morphine-induced tolerance in mice and discover its underlying mechanism. Tail-flick assay and hot-plate test were conducted to assess the development of tolerance to morphine-induced analgesia effect. As a result of repeated administration scheme (10 mg/kg, twice per day, for 7 days), approximately a two-fold increase was observed in the effective dose of 50% (ED50) of morphine-induced antinociceptive effect. Interestingly, by EA treatment (2/100Hz, 0.5, 1.0, and 1.5 mA, 30 min/day for 7 days) at the acupoints Zusanli (ST36) and Sanyinjiao (SP6), morphine ED50 curves was remarkably leftward shifted on day 8. In addition, the RNA sequencing strategy was used to reveal the potential mechanisms. Due to the well described relevance of cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), extracellular regulated protein kinases (ERK), and cAMP response element-binding (CREB) in brainstem (BS) to analgesia tolerance, the cAMP-PKA/ERK-CREB signaling was deeply concerned in this study. Based upon Enzyme-Linked Immunosorbent Assay, the up-regulation of the cAMP level was observed, whereas reversed with EA treatment. Similarly, western blot revealed the phosphorylation levels of PKA, ERK, and CREB were up-regulated in morphine tolerant mice, whereas the EA group showed a significantly reduced expression level instead. This study observed an attenuating effect of the EA at ST36 and SP6 on morphine tolerance in mice, and suggested several potential biological targets by RNA-seq, which include the cAMP-PKA/ERK-CREB signaling pathway, strongly supporting a useful treatment for combatting the opioid epidemic, and opioid-tolerant patients.

This study aimed to assess whether protective measures could reduce the health risks of air pollution in mice living in the chambers situated at a suburban site in Beijing. The living chambers of mice were divided into four groups: male mice with and without the high-efficiency particulate air (HEPA) filter (male group A and group B), as well as female mice with and without the HEPA filter (female group A and group B). The experiment was carried out from 1 December 2017 to 31 May 2018. Parameters of respiratory function during periods of clean air and air pollution were determined for all groups to evaluate the role of the indoor air filter (i.e., HEPA) in protection against respiratory health risks in mice. Significant differences in minute volumes were observed in male and female groups with versus without the HEPA. Additionally, respiratory health parameters including respiratory rate, duration of breaking, expiratory time, and relaxation time exhibited differences in female groups with HEPA versus without HEPA. Levels of inflammatory factors in the lungs were measured for all groups after 6months of exposure. Greater mean levels of IL-6 and TNF-α were found in the male groups without HEPA than in those with HEPA. Higher average concentrations of IL-6, T-AOC, SOD, GSH-Px, LDH, TNF-α, and TGF-β1 were found in the female group without HEPA than those without HEPA. Our study has proved the effective protection provided by indoor air filters (i.e., HEPA filters) in reducing respiratory health risks associated with PM2.5.

The Coronavirus Disease 2019 has resulted in a transition from physical education to online learning, leading to a collapse of the established educational order and a wisdom test for the education governance system. As a country seriously affected by the pandemic, the health of the Indian higher education system urgently requires assessment to achieve sustainable development and maximize educational externalities. This research systematically proposes a health assessment model from four perspectives, including educational volume, efficiency, equality, and sustainability, by employing the Technique for Order Preference by Similarity to an Ideal Solution Model, Principal Component Analysis, DEA-Tobit Model, and Augmented Solow Model. Empirical results demonstrate that India has high efficiency and an absolute health score in the higher education system through multiple comparisons between India and the other selected countries while having certain deficiencies in equality and sustainability. Additionally, single-target and multiple-target path are simultaneously proposed to enhance the Indian current education system. The multiple-target approach of the India-China-Japan-Europe-USA process is more feasible to achieve sustainable development, which would improve the overall health score from .351 to .716. This finding also reveals that the changes are relatively complex and would take 91.5 years considering the relationship between economic growth rates and crucial indicators. Four targeted policies are suggested for each catching-up period, including expanding and increasing the social funding sources, striving for government expenditure support to improve infrastructures, imposing gender equality in education, and accelerating the construction of high-quality teachers.

Intracellular transport relies on multiple kinesins, but it is poorly understood which kinesins are present on particular cargos, what their contributions are and whether they act simultaneously on the same cargo. Here, we show that Rab6-positive secretory vesicles are transported from the Golgi apparatus to the cell periphery by kinesin-1 KIF5B and kinesin-3 KIF13B, which determine the location of secretion events. KIF5B plays a dominant role, whereas KIF13B helps Rab6 vesicles to reach freshly polymerized microtubule ends, to which KIF5B binds poorly, likely because its cofactors, MAP7-family proteins, are slow in populating these ends. Sub-pixel localization demonstrated that during microtubule plus-end directed transport, both kinesins localize to the vesicle front and can be engaged on the same vesicle. When vesicles reverse direction, KIF13B relocates to the middle of the vesicle, while KIF5B shifts to the back, suggesting that KIF5B but not KIF13B undergoes a tug-of-war with a minus-end directed motor.

Abstract Background Border malaria, a shared phenomenon in the Greater Mekong Sub-region of Southeast Asia, is a major obstacle for regional malaria elimination. Along the China–Myanmar border, an additional problem arose as a result of the settlement of internally displaced people (IDP) in the border region. Since asymptomatic malaria significantly impacts transmission dynamics, assessment of the prevalence, dynamics and risk factors of asymptomatic malaria infections is necessary. Methods Cross-sectional surveys were carried out in 3 seasons (March and April, July and November) and 2 sites (villages and IDP camps) in 2015. A total of 1680 finger-prick blood samples were collected and used for parasite detection by microscopy and nested RT-PCR (nRT-PCR). Logistic regression models were used to explore the risk factors associated with asymptomatic malaria at individual and household levels. Results The prevalence of asymptomatic Plasmodium infections was 23.3% by nRT-PCR, significantly higher than that detected by microscopy (1.5%). The proportions of Plasmodium vivax, Plasmodium falciparum and mixed-species infections were 89.6, 8.1 and 2.3%, respectively. Asymptomatic infections showed obvious seasonality with higher prevalence in the rainy season. Logistic regression analysis identified males and school children (≤ 15 years) as the high-risk populations. Vector-based interventions, including bed net and indoor residual spray, were found to have significant impacts on asymptomatic Plasmodium infections, with non-users of these measures carrying much higher risks of infection. In addition, individuals living in poorly constructed households or farther away from clinics were more prone to asymptomatic infections. Conclusions Sub-microscopic Plasmodium infections were highly prevalent in the border human populations from IDP camps and surrounding villages. Both individual- and household-level risk factors were identified, which provides useful information for identifying the high-priority populations to implement targeted malaria control.

Air pollution and climate change are key global challenges for cities and both have large impacts on human health and economic development. Although there are many long term opportunities to address these issues with integrated policies, the immediate needs of addressing air pollution and climate change mitigation are not the same for all countries in the short run. We examined the relationships between greenhouse gases (GHG) emissions, outdoor air pollution, and levels of socioeconomic development to identify specific near-term mitigation policy responses to climate change and air pollution for countries with different levels of human development. Human development index, as defined by The United Nations Development Programme (UNDP) is a measure of achievement in the basic dimensions of human development across countries, which combines the gross national income index, an education index and a life expectancy index (http://hdr.undp.org/en/humandev). Country-level data were collected on indicators of socioeconomic development, emissions of GHG, and outdoor levels of fine particulate matter (PM2.5) from the World Bank, the UNDP, and the Task Force on Hemispheric Transport of Air Pollution. Differences in GHG emissions and air pollution concentrations, as well as socioeconomic development indicators, were assessed at national, sub-national, and global scales. Countries were divided into four categories based on CO2 emissions per capita and an estimation of outdoor PM2.5: Group A was characterized by high CO2 emissions per capita and low PM2.5 concentrations, Group B by high CO2 emissions per capita and high PM2.5 concentrations, Group C by low CO2 emissions per capita and low PM2.5 concentrations, and Group D by low CO2 emissions per capita and high PM2.5 concentration. Per-capita emissions of CO2 were strongly correlated with the level of socioeconomic development, while differences in non-CO2 greenhouse gas emissions per capita across the groups were not correlated. Atmospheric PM2.5 concentrations were not correlated with either CO2 emissions per capita or levels of socioeconomic development. Energy and environmental policies focused on CO2 emission reductions may not inherently lead to development pathways that sufficiently reduce population exposure to air pollution. Countries with low CO2 and high air pollution levels should pursue short-term policies to reduce air pollution and increase human development, beginning to address GHG emissions after critical human health and development needs are met.

Sexual reproduction is an essential process in the Plasmodium life cycle and a vulnerable step for blocking transmission from the human host to mosquitoes. In this study, we characterized the functions of a conserved cell membrane protein P115 in the rodent malaria parasite Plasmodium berghei ANKA. Pb115 was expressed in both asexual stages (schizonts) and sexual stages (gametocytes, gametes, and ookinetes), and was localized on the plasma membrane of gametes and ookinetes. In P. berghei, genetic deletion of Pb115 (Δpb115) did not affect asexual multiplication, nor did it affect gametocyte development or exflagellation of the male gametocytes. However, mosquitoes fed on Δpb115-infected mice showed 74% reduction in the prevalence of infection and 96.5% reduction in oocyst density compared to those fed on wild-type P. berghei-infected mice. The Δpb115 parasites showed significant defects in the interactions between the male and female gametes, and as a result, very few zygotes were formed in ookinete cultures. Cross fertilization with the male-defective Δpbs48/45 line and the female-defective Δpfs47 line further indicated that the fertilization defects of the Δpb115 lines were present in both male and female gametes. We evaluated the transmission-blocking potential of Pb115 by immunization of mice with a recombinant Pb115 fragment. In vivo mosquito feeding assay showed Pb115 immunization conferred modest, but significant transmission reducing activity with 44% reduction in infection prevalence and 39% reduction in oocyst density. Our results described functional characterization of a conserved membrane protein as a fertility factor in Plasmodium and demonstrated transmission-blocking potential of this antigen.

Research Findings: Research with older children and adults reliably demonstrates that individuals raised in poverty tend to evaluate concerns related to moral concerns (i.e., related to harm, welfare, and justice) differently than do wealthier individuals. However, little work has examined these patterns in young children. Children (N=214, Mage = 53.30 months, SD = 18.3 months) completed tasks regarding accidental and prototypic moral transgressions, and a standard verbal assessment. Parents reported family size and household income, which were used to compute individuals' income-to-needs ratio (INR) compared to federal standards. Using generalized linear mixed modeling (GLMM), a repeated-measure analysis, results indicate that children in low-income families (INR < 2.0) were more lenient in how they evaluate both accidental and prototypic issues, compared to more affluent children. Moreover, they were more likely to evaluate issues based on communal welfare (e.g., equitable resource distribution), whereas more affluent children were more likely to reference psychological harm. Practice or Policy: Practitioners and researchers of early childhood should be cognizant and sensitive to differences in children's social understanding. We encourage scholars to use a strength-based, adaptive approach in future research on children's cognition, particularly involving SES, class, and the like.

Neuronal differentiation is a multistep process that shapes and re-shapes neurons by progressing through several typical stages, including axon outgrowth, dendritogenesis, and synapse formation. To systematically profile proteome dynamics throughout neuronal differentiation, we took cultured rat hippocampal neurons at different developmental stages and monitored changes in protein abundance using a combination of stable isotope labeling and high-resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS). Almost one third of all 4,500 proteins quantified underwent a more than 2-fold expression change during neuronal differentiation, indicating extensive remodeling of the neuron proteome. To highlight the strength of our resource, we studied the neural-cell-adhesion molecule 1 (NCAM1) and found that it stimulates dendritic arbor development by promoting actin filament growth at the dendritic growth cone. We anticipate that our quantitative map of neuronal proteome dynamics is a rich resource for further analyses of the many identified proteins in various neurodevelopmental processes.

Corrosion inhibitors are one of the most effective anticorrosion techniques in reinforced concrete structures. Molecule dynamics (MD) was usually utilized to simulate the interaction between the inhibitor molecules and the surface of Fe to evaluate the inhibition effect, ignoring the influence of cement hydration products. In this paper, the adsorption characteristics of five types of common alkanol-amine inhibitors on C-S-H gel in the alkaline liquid environment were simulated via the MD and the grand canonical Monte Carlo (GCMC) methods. It is found that, in the MD system, the liquid phase environment had a certain impact on the adsorption configuration of compounds. According to the analysis of the energy, the binding ability of MEA on the surface of the C-S-H gel was the strongest. In the GCMC system, the adsorption of MEA was the largest at the same temperature. Furthermore, for the competitive adsorption in the GCMC system, the adsorption characteristics of the inhibitors on the C-S-H gel were to follow the order: MEA>DEA>TEA>NDE>DETA. Both MD and GCMC simulations confirmed that the C-S-H gel would adsorb the organic inhibitors to a different extent, which might have a considerable influence on the organic inhibitors to exert their inhibition effects.

Medium Mn steels have been considered as the next-generation materials for use in the automotive industry due to their excellent strength and ductility balance. To reduce the total weight and improve the safety of vehicles, medium Mn steels look forward to a highly promising future. However, hydrogen-induced delayed cracking is a concern for the use of high strength steels. This work is focused on the service characteristics of two kinds of medium Mn steels under different relative humidity conditions (40%, 60%, 80% and 100%). Under normal relative humidity (about 40%) at 25 °C, the hydrogen concentration in steel is 0.4 ppm. When exposed to higher relative humidity, the hydrogen concentration in steel increases slowly and reaches a stable value, about 0.8 ppm. In slow strain rate tensile tests under different relative humidity conditions, the tensile strength changed, the hydrogen concentration increased and the elongation decreased as well, thereby increasing the hydrogen embrittlement sensitivity. In other words, the smaller the tensile rate applied, the greater the hydrogen embrittlement sensitivity. In constant load tests under different relative humidity conditions, the threshold value of the delayed cracking of M7B (‘M’ referring to Mn, ‘7’ meaning the content of Mn, ‘B’ denoting batch annealing) steel maintains a steady value of 0.82 σb (tensile strength). The threshold value of the delayed cracking of M10B significantly changed along with relative humidity. When relative humidity increased from 60% to 80%, the threshold dropped sharply from 0.63 σb to 0.52 σb. We define 80% relative humidity as the ‘threshold humidity’ for M10B.

Microtubules are dynamic polymers that in cells can grow, shrink or pause, but the factors that promote pausing are poorly understood. Here, we show that the mammalian kinesin-4 KIF21B is a processive motor that can accumulate at microtubule plus ends and induce pausing. A few KIF21B molecules are sufficient to induce strong growth inhibition of a microtubule plus end in vitro. This property depends on non-motor microtubule-binding domains located in the stalk region and the C-terminal WD40 domain. The WD40-containing KIF21B tail displays preference for a GTP-type over a GDP-type microtubule lattice and contributes to the interaction of KIF21B with microtubule plus ends. KIF21B also contains a motor-inhibiting domain that does not fully block the interaction of the protein with microtubules, but rather enhances its pause-inducing activity by preventing KIF21B detachment from microtubule tips. Thus, KIF21B combines microtubule-binding and regulatory activities that together constitute an autonomous microtubule pausing factor.

Electrochemical chloride removal (ECR) from reinforced concrete can be considered as an environment-friendly technique since it can reduce the environmental issues arising from demolition and reconstruction. In this study, we used ultrasonic waves to promote the ECR efficiency without increasing the current density so as to shorten the overall power-on time, lowering the power consumption and electricity-induced material damage. Rebar-embedded cement mortar specimens were prepared and a set of ultrasonic-assisted ECR test devices was designed. For obtaining the optimal parameters, different ultrasonic frequencies and powers were adopted to conduct the ECR test. After that, the discharged and residual chloride ion amounts were detected to characterize the ECR efficiency. The corrosion behavior of rebar was characterized by electrochemical method. It was found that ultrasonic waves can not only promote the discharge of chloride ions, but also promote the passivation process of steel bar. For this investigation, the ultrasonic waves with a frequency of 40 Hz and a power of 60 W had the best auxiliary effect and could reduce the work time by 64%. It is considered that the ultrasound-assisted method has potential to promote the application possibilities of the ECR technique.

The addition of expansive agents could overcome the main disadvantages of raw concrete including high brittleness and low tensile strength. Few studies have investigated the early hydration kinetics of expansive cementitious binders, though the findings from the early hydration kinetics are helpful for understanding their technical performances. In this study, mixtures of 3CaO•3Al2O3•CaSO4 and CaSO4 (i.e., ZY-type™ expansive agent) with different proportions of mineral admixtures (e.g., fly ash and slag) were added into cement pastes to investigate the early hydration kinetics mechanism of expansive cementitious binders. Early hydration heat evolution rate and cumulative hydration heat were measured by isothermal calorimeter. Kinetic parameters were estimated based on the Krstulovic−Dabic model and Knudsen equations. Mechanical performances of expansive cementitious binders were tested in order to evaluate if they met the basic requirements of shrinkage-compensating materials in technical use. The early hydration heat released from cementitious binders containing ZY-type™ expansive agent was much greater than that released by pure cement, supporting the idea that addition of the expansive agent would improve the reaction of cement. The early hydration kinetic rates were decreased due to the reactions of the mineral admixture (e.g., fly ash or slag) and the ZY-type™ expansive agent in the cement system. The hydration reaction of cementitious binders containing ZY-type™ expansive agent obeyed the Krstulovic−Dabic model well. Three processes are involved in the hydration reaction of cementitious binders containing ZY-type™ expansive agent. These are nucleation and crystal growth (NG), interactions at phase boundaries (I), and diffusion (D). The 14-day expansion rates of cementitious binders containing ZY-type™ expansive agent are in the range of 2.0 × 10−4 to 3.5 × 10−4, which could meet the basic requirements of anti-cracking performances in technical use according to Chinese industry standard JGJ/T 178-2009. This study could provide an insight into understanding the effects of expansive agents on the hydration and mechanical performances of cementitious binders.