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Objective: The current systematic review and meta-analysis assessed the prevalence of central precocious puberty (CPP) throughout the novel coronavirus disease 2019 (COVID-19) pandemic., Design: A systematic review and meta-analysis were carried out following the principles outlined by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA, 2020)., Data Sources: PubMed, Embase, Web of Science, and WANFANG databases were searched from January 1, 2019, to March 30, 2023., Eligibility Criteria for Selecting Studies: (1) children and adolescents ≤ 15 years; (2) studies with the outcome of frequency of central precocious puberty, measured prior to and throughout the COVID-19 pandemic; (3) a novel CPP diagnosis was created depending on all of the following criteria: girls with a chronological age < 8 years and boys with a chronological age < 9 years at the onset of symptoms, basal luteinizing hormone (LH) levels > 0.3 UI/L, and/or GnRH-stimulated peak LH levels > 5 IU/L., Data Extraction and Synthesis: The process of extracting data and evaluating the likelihood of bias was carried out by two independent reviewers. The data were pooled employing the generic inverse-variance method and presented as mean differences (MDs) with 95% CIs. The evaluation of heterogeneity was conducted employing the Cochran Q statistic, and the degree of heterogeneity was measured employing the I 2 statistic., Results: This meta-analysis included 17 studies. In contrast to the same period prior to the COVID-19 pandemic, the occurrence of CPP elevated (OR = 2.57; 95% CI, 1.85-3.56). Moreover, body mass index standard deviation score (BMI SDS) differences between CPP patients prior to COVID-19 and throughout the pandemic follow-up was 0.12 (95% CI - 0.01 to 0.25 P = 0.06)., Conclusion: Overall, CPP frequency significantly elevated throughout the COVID-19 pandemic. Given the restricted number of cohort investigations in this meta-analysis, additional research may be conducted on larger groups of children in order to establish a correlation between the observed rise in precocious puberty and specific pathogenic factors., (© 2024. The Author(s).)

The therapeutic efficacy of oncolytic adenoviruses (OAs) relies on efficient viral transduction and replication. However, the limited expression of coxsackie-adenovirus receptors in many tumors, along with the intracellular antiviral signaling, poses significant obstacles to OA infection and oncolysis. Here, we present sonosensitizer-armed OAs (saOAs) that potentiate the antitumor efficacy of oncolytic virotherapy through sonodynamic therapy-augmented virus replication. The saOAs could not only efficiently infect tumor cells via transferrin receptor-mediated endocytosis but also exhibit enhanced viral replication and tumor oncolysis under ultrasound irradiation. We revealed that the sonosensitizer loaded on the viruses induced the generation of ROS within tumor cells, which triggered JNK-mediated autophagy, ultimately leading to the enhanced viral replication. In mouse models of malignant melanoma, the combination of saOAs and sonodynamic therapy elicited a robust antitumor immune response, resulting in significant inhibition of melanoma growth and improved host survival. This work highlights the potential of sonodynamic therapy in enhancing the effectiveness of OAs and provides a promising platform for fully exploiting the antitumor efficacy of oncolytic virotherapy.

DNA vaccines represent an innovative approach for the immunization of diverse diseases. However, their clinical trial outcomes are constrained by suboptimal transfection efficiency and immunogenicity. In this work, we present a universal methodology involving the codelivery of Toll-like receptor 7/8 agonists (TLR7/8a) and antigen gene using TLR7/8a-conjugated peptide-coated poly(β-amino ester) (PBAE) nanoparticles (NPs) to augment delivery efficiency and immune response. Peptide-TLR7/8a-coated PBAE NPs exhibit advantageous biophysical attributes, encompassing diminutive particle dimensions, nearly neutral ζ potential, and stability in the physiological environment. This synergistic approach not only ameliorates the stability of plasmid DNA (pDNA) and gene delivery efficacy but also facilitates subsequent antigen production. Furthermore, under optimal formulation conditions, the TLR7/8a-conjugated peptide coated PBAE NPs exhibit a potent capacity to induce robust immune responses. Collectively, this nanoparticulate gene delivery system demonstrates heightened transfection efficacy, stability, biodegradability, immunostimulatory effect, and low toxicity, making it a promising platform for the clinical advancement of DNA vaccines.

Supercritical pseudoboiling was proposed in the 1950s-1960s. Recently, evaporation-like and boiling-like heat transfer have been directly observed in macroscopic scales, and the contribution of pseudoboiling to the total heat transfer rate has been quantitatively characterized experimentally. Here, we explore the critical threshold to generate a bubble-like nucleus at supercritical pressure at the atomic scale, characterized by the total energy (Te = Ke + Pe, where Ke and Pe are kinetic energy and potential energy, respectively). Molecular dynamics simulations are performed, including an argon fluid box heated by a solid wall having its temperature above the fluid temperature. The fluid pressure is controlled by a movable piston wall opposite the heating wall. The effects of pressure, nonuniform heating, and surface wettability on pseudoboiling are investigated. It is found that the criterion Te > 0 should be satisfied for subcritical boiling, matching that reported previously. The criterion for supercritical pseudoboiling was newly obtained such that Te > 0.012 eV at 8 MPa for argon, but the threshold increases as pressure increases. Nonuniform heating and surface wettability do not affect the critical threshold of Te for bubble-like nucleation but affect the location of the initially generated bubble-like nucleus and the stabilized pseudofilm or pseudonucleate heat transfer modes, where the former is similar to (vapor) film boiling and the latter is similar to nucleate boiling at subcritical pressure. Because pseudoboiling occurs without surface tension at supercritical pressure, we observe that the bubble-like structure may not display a perfectly smooth gas-liquid interface but may display an irregular pattern instead. Our work explains pseudoboiling from the viewpoint of the competition between kinetic energy and potential energy and presents a link regarding boiling in the two domains of subcritical pressure and supercritical pressure.

Background: Psoriasis is a common chronic, recurrent, and inflammatory skin disease. Identifying novel and potential biomarkers is valuable in the treatment and diagnosis of psoriasis. The goal of this study was to identify novel key biomarkers of psoriasis and analyze the potential underlying mechanisms., Methods: Psoriasis-related datasets were downloaded from the Gene Expression Omnibus database to screen differential genes in the datasets. Functional and pathway enrichment analyses were performed on the differentially expressed genes (DEGs). Candidate biomarkers for psoriasis were identified from the GSE30999 and GSE6710 datasets using four machine learning algorithms, namely, random forest (RF), least absolute shrinkage and selection operator (LASSO) logistic regression, weighted gene co-expression network analysis (WGCNA), and support vector machine recursive feature elimination (SVM-RFE), and were validated using the GSE41662 dataset. Next, we used CIBERSORT and single-cell RNA analysis to explore the relationship between ADAM23 and immune cells. Finally, we validated the expression of the identified biomarkers expressions in human and mouse experiments., Results: A total of 709 overlapping DEGs were identified, including 426 upregulated and 283 downregulated genes. Enhanced by enrichment analysis, the differentially expressed genes (DEGs) were spatially arranged in relation to immune cell involvement, immune-activating processes, and inflammatory signals. Based on the enrichment analysis, the DEGs were mapped to immune cell involvement, immune-activating processes, and inflammatory signals. Four machine learning strategies and single-cell RNA sequencing analysis showed that ADAM23, a disintegrin and metalloprotease, may be a unique, critical biomarker with high diagnostic accuracy for psoriasis. Based on CIBERSORT analysis, ADAM23 was found to be associated with a variety of immune cells, such as macrophages and mast cells, and it was upregulated in the macrophages of psoriatic lesions in patients and mice., Conclusion: ADAM23 may be a potential biomarker in the diagnosis of psoriasis and may contribute to the pathogenesis by regulating immunological activity in psoriatic lesions., Competing Interests: The authors declare that there are no conflicts of interest., (© 2023 Yao et al.)

To increase the boiling heat transfer limit, we disrupted the previously nonevaporating region and increased the vaporization activity of "inert" liquid molecules by introducing nano ridges on the boiling surface. This solved the paradox of no heat transfer occurring through the thinnest liquid film in boiling bubbles; thus, the internal heat transfer limit of the bubbles was exceeded. We found that vigorous boiling occurred immediately once the nonevaporating region was activated, and the bubble frequency increased by an order of magnitude, reaching 1186 Hz, which has not been previously reported. With an increase in heat flux, the boiling curve exhibited a "return". We achieved an extremely high bubble frequency by experimentally quantifying the major influence of nonevaporating region disruption on boiling heat transfer. The mechanism behind the generation of the ultrahigh-frequency bubbles was discovered. This study also reveals a new mechanism for the reversed boiling curve.

Low-speed driving is an underestimated dangerous behavior that may cause safety issues, such as speed dispersion and traffic flow bottlenecks. To investigate the influence mechanism of low-speed driving behavior, this study constructed the low-speed specific model (LSSM) by extending theory of planned behavior (TPB). The LSSM incorporated two factors, namely, risk perception and behavior habit, into the standard TPB components (attitude, subjective norm, perceived behavioral control, and behavior intention). Web-based questionnaires were used to collect data from a valid sample of 374, of which males accounted for 50%. The participants were aged from 18 to 65 years (M = 35.40, SD = 0.88). The structural equation model was applied to calculate and validate the interrelationships among the components of LSSM. Results showed that the LSSM could explain the variance in low-speed driving behavior and behavior intention by 46% and 76%, respectively. Meanwhile, attitude (β = 0.52, p < 0.001) and behavior habit (β = 0.48, p < 0.001) had the strongest positive influence and prediction power over low-speed driving behavior, respectively, whereas subjective norm (β = 0.05, p > 0.01) and perceived behavioral control (β = -0.12, p > 0.01) showed few significant in influencing the intention. LSSM also showed that people who were sensitive to driving risk perception would avoid low-speed driving behaviors and attitudes. Our findings may provide theoretical support for interventions on low-speed driving behavior., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In emergency scenarios, lane changing can provide a considerable advantage over braking by aiding in the prevention of rear-end collisions. However, executing lane changes on horizontal curves might lead to rollover collisions. This study proposes a systematic methodology for quantifying the rollover safety margin during lane-changing maneuvers by encompassing the complex characteristics of vehicle-road interactions. Specifically, an enhanced six-degree-of-freedom vehicle dynamics model was developed for a tractor-semitrailer and integrates road superelevation. Using this model, the rollover safety margin reduction rate (fS) was calculated. The fS represents the ratio of the difference between the lateral load transfer ratio margins under both reference state and emergency lane change conditions to the lateral load transfer ratio margin in the reference state. The reference state corresponds to vehicles maintaining 80 km·h-1 on a 270 m radius curve, while the emergency condition is defined as lane change durations of less than 4 seconds. The results reveal that emergency lane change maneuvers and roadway alignment significantly affect rollover safety margin. Shorter lane change duration, higher speed, and smaller radius worsen the rollover safety margin; these effects are further amplified when the lane change direction is opposite to the curve's bending direction. When the tractor-semitrailer performs a lane change at 60 km·h-1 within a 4-second duration on a 600 m radius curve, the fS exceeds 100%, indicating an imminent rollover. Consequently, this study contributes valuable evidence to the development of more reliable and secure lane-change strategies., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Lv et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study investigates whether serum prolactin (PRL) is a key factor for nonalcoholic fatty liver disease (NAFLD) in children. A total of 691 obese childred participated in this study and were divided into a NAFLD group (n=366) and simple obesity (SOB) group (n=325) according to the hepatic ultrasound results. The two groups were matched for gender, age, pubertal development, and body mass index (BMI). All patients underwent an OGTT test, and fasting blood samples were collected to measure prolactin. Stepwise logistic regression was performed to identify significant predictors of NAFLD. Serum prolactin levels were significantly lower in NAFLD subjects than in the SOB subjects [82.4 (56.36, 118.70) vs. 99.78 (63.89, 153.82), p<0.001] (mIU/l). NAFLD was strongly associated with insulin resistance (HOMA-IR) and prolactin, with lower levels of prolactin increasing the risk of NAFLD (adjusted ORs=1.741; 95% CI: 1.059-2.860) across the prolactin concentration tertiles after adjustment for confounders. Low serum prolactin levels are associated with the presence of NAFLD; thus, increased circulating prolactin might be a compensatory response for obesity in children., Competing Interests: The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Carbon emission changes significantly when the vehicle is driving at a variable speed. Given that the rule of vehicle carbon emissions under different driving behaviors is underexplored, this study filled this research gap by establishing a theoretical carbon emission model when vehicles are driving at fluctuating speed. The model was established based on the law of conservation of mechanical energy, the first law of thermodynamics, the theory of vehicle dynamics. Two passenger cars and three trucks were selected as typical vehicles. A field test was carried out under different driving behaviors with uniform acceleration. The proposed model can forecast the carbon emissions of vehicles that fluctuate in speed during travel and showed strong accuracy in model validation. As the speed fluctuation increased, the influence of acceleration on carbon emissions became more apparent. Gradient has a more significant influence on vehicle carbon emissions, followed by acceleration. By controlling the driving behavior of the vehicle on the round trip, the same carbon emissions as driving on a flat route at a constant speed can be achieved. The findings of this study will provide a theoretical basis for low-carbon transportation., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Glioblastoma is the most common type of primary brain tumor, which has a high recurrence rate and a high mortality rate. Immunotherapy shows promise in cancer therapy due to its capacity to manipulate the immune system to attack tumor cells with less toxic and durable immune responses. However, the low immunogenicity and limited immune cell infiltration in a glioblastoma lead to a weakened antitumor immune response, resulting in suboptimal therapeutic efficacy. A compelling solution is provided by oncolytic adenovirus (OAs), which can selectively replicate within tumor cells while simultaneously promoting antitumor immunity. Herein, we constructed an oncolytic adenovirus reservoir (OAR) by shocking OA-loaded tumor cells in liquid nitrogen to eliminate proliferation and pathogenicity. OARs showed sustained OAs release and effectively lysed tumor cells in vitro and in vivo. In a mouse intracranial glioblastoma model, OARs could efficiently induce dendritic cells' maturation, facilitate the tumor recruitment, and promote the infiltration of cytotoxic effector T lymphocytes via a single treatment, resulting in specific antitumor immune responses and long-term animal survival. Taken together, these results demonstrated that OAR is a promising synergistic therapeutic strategy for treating glioblastoma.

Hypothesis: Nanostructured materials are widely used for solar energy harvesting and conversion due to their excellent photothermal properties. It is generally accepted that the better the light absorption ability, the better the photothermal conversion efficiency., Experiment: A series of experiments in solar evaporation of liquid marbles (LMs) by coating the droplets with Fe 3 O 4 , Ni nanoparticles (NPs) and carbon nanotubes (CNTs) are conducted., Findings: Conversely, we found that the surface roughness of solar absorber plays a significant role in solar evaporation rather than the light absorption. The results disclose that the Fe 3 O 4 NPs with the lowest absorptivity has the largest roughness on drop surface, while that of CNTs show the opposite properties. The evaporation dynamics of LMs are featured with dome or constant spherical collapse with different roughness. Such dynamic difference arises from the mechanical competition between the capillary force and interparticle interaction. Besides, the strong light-harvesting and near-field radiation enabled by the rough surfaces enhance the solar evaporation. The Fe 3 O 4 -LM shows the highest evaporation rate of 6.55 μg/s, which is 1.09 and 1.30 times larger than that of Ni-LM and CNT-LM, respectively. Numerical analysis reveals that the rough surface with stacking arrangement of NPs greatly enhances the light-induced electromagnetic field and heat concentration over the interface, leading to a plasmon-coupling boundary with high temperature for the fast evaporation. Uncovering these properties could be of much help for developments of heatable miniature evaporators or reactors and their counterparts, permitting a broad range of processes with precise temperature and kinetic control., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The extent to which drivers' collision avoidance maneuvers affect the safety margins of sideslip and rollover is not captured by road geometric design theory. To quantify the effects of drivers' collision avoidance maneuvers on the safety margins of sport utility vehicles (SUVs) on horizontal curve and grade combinations, a modified 8-degree-of-freedom multibody model based on SUVs was developed. The model was then used to calculate the design safety margins of sideslip and rollover for steady states and the actual safety margins for collision avoidance maneuvers. Subsequently, the design safety margin reduction rate (the difference between the design and actual safety margins divided by the design safety margin) was calculated and used to assess the safety margins. The results showed that the safety margins of SUVs were significantly reduced by braking, lane changing, and lane changing with braking. The marginal effects indicated that the greater the deceleration and the shorter the lane change duration, the greater the effect on the safety margins, particularly the sideslip safety margin. Furthermore, when the SUV was driven at 80 km·h -1 on grades with a horizontal curve radius of 270 m and 400 m, the sideslip safety margin with emergency braking (deceleration over -4.5 m·s -2 ) was reduced by 71% and 21%, and the rollover safety margin was reduced by 11% and 5%, respectively. Under these conditions, an emergency lane change (lane change duration less than 2 s) caused the SUV to sideslip and reduced the rollover safety margin by 47% (curve radius 270 m) and 45% (curve radius 400 m). Therefore, drivers' collision avoidance maneuvers are a factor that cannot be neglected in alignment design.

Roadway multi-fatality crashes have always been a vital issue for traffic safety. This study aims to explore the contributory factors and interdependent characteristics of multi-fatality crashes using a novel framework combining association rules mining and rules graph structures. A case study is conducted using data from 1068 severe fatal crashes in China from 2015 to 2020, and 1452 interesting rules are generated using an association rule mining approach. Several modular rules graph structures are constructed based on graph theory to reflect the interactions and patterns between different variables. The results indicate that multi-fatality crashes are highly associated with improper operations, passenger overload, fewer lanes, mountainous terrain, and run-off-the-road crashes, representing the key variables of factors concerning driver, vehicle, road, environment, and accident, respectively. Furthermore, crashes involving different severity levels, road categories, and terrain are verified to possess unique association rules and independent crash patterns. Moreover, the proportion of severe crashes caused by a combination of human-vehicle-road-environment factors (43%) is much higher than that of normal crashes (3%). This study reveals that the hidden associations between various factors contribute to the overrepresentation and severity of multi-fatality crashes. It also demonstrates that the crash mechanisms involving multi-fatality crashes and their interactions are more complex at the system level than those for normal crashes. The proposed framework can effectively map the intrinsic link between multiple crash factors and potential risks, providing transportation agencies with helpful insights for targeted safety measures and preventive strategies., Competing Interests: The authors have declared that no competing interests exist.

Aim: Non-alcoholic fatty liver disease (NAFLD) is currently the most prevalent liver disease in the world, increasing the risk of cirrhosis and hepatocellular carcinoma, and contributing to the development of type 2 diabetes, cardiovascular disease, and chronic kidney disease. This study aims to carry out a web-based continuum of a care intervention model to provide comprehensive care interventions for obese children with NAFLD, to improve the effectiveness of treatment of children with NAFLD., Design: A 1-year single-blinded randomized clinical trial in hospital in Zhejiang Province., Methods: Eighty subjects will implement the program in a randomized order. The interventions for the control group mainly consisted of the routine distribution of health education materials and health education by holding health-themed lectures, and the preliminary proposed interventions including establishing management teams, regularly delivering related health knowledge, daily uploading of health intervention records, regular supervision and mutual encouragement, home visiting and psychological guidance. The primary outcomes are serum biomarkers such as alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT), aspartate aminotransferase, and imaging (liver ultrasound and magnetic resonance imaging). Second outcomes are: BMI, waist-to-hip ratio and quality of life. In addition, socio-demographic characteristics such as age, gender and ethnicity will be recorded. Children aged 7-18 years old and diagnosed with NAFLD will be included, patients will be not eligible if they do not agree to participate or are participating in other health intervention programs. This study was registered on ClinicalTrials.gov (NCT05527938)., Results: Over the past 30 years, NAFLD has been recognized as one of the most common liver diseases in adults and children. The current studies have focused on promoting lifestyle changes in children with NASH by providing some education and advice to children and their families to improve the histological features of NASH and lose weight. Because of the convenience and efficiency of the internet can provide some new strategies and ways for lifestyle interventions for children with NAFLD. In addition, we have designed a high-quality RCT based on the SPIRIT guidelines, which also provides strong evidence in this area., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tian, Xu, Wang, Yu and Tang.)

Road traffic safety can be ensured by preventing and controlling the potential risks in road traffic operations. The relevant literature was systematically reviewed to identify the research context and status quo in the road traffic operation risk prevention and control field and identify the key study contents needing further research. As research material, the related English and Chinese literature published between 1996 and 2021 (as of 31st December 2021) was obtained through the Web of Science Core Collection and Chinese Science Citation Database. These research materials include 22,403 English and 7876 Chinese papers. Based on the bibliometrics, this study used CiteSpace software to conduct keyword co-occurrence analysis in the field. The results show that the relevant research topics mainly covered the risks of drivers, vehicles, roads, and the traffic environment. In the aspect of driver risks, the studies focused on driving behavior characteristics. In terms of vehicle risks, the related studies were mainly about the vehicle control system, driving assistance system, hazardous material transportation, automated driving technology, safe driving speed, and vehicle collision prediction. For the road risks, the safe driving guarantee of high-risk road sections, driving risks at intersections, and safe road alignment design were the three study hotspots. In terms of traffic environment risks, identifying traffic risk locations and driving safety guarantees under adverse weather conditions were the two main research highlights. Moreover, mathematical modeling was the main method for studying road traffic operation risk. Furthermore, the impact of environmental factors on drivers, the emergency rescue system for road traffic accidents, the connection between automated driving technology and safe driving theory, and the man-machine hybrid traffic flow characteristics are the subjects needing further research.

The friction coefficient between the tire and the road is one of the key parameters affecting road traffic safety. The purpose of this paper is to quantify the risk of skidding for the vehicles due to the friction evolution caused by the traffic polishing in the horizontal curve. Based on the reliability theory, an innovative dynamic risk assessment model is developed in the present study for passenger cars and trucks. The influence of two traffic characteristics for pavement friction is quantified: cumulative traffic volume (CTV) and annual average daily traffic of trucks (AADTT). The speed distribution on the horizontal curve of the motorway is obtained through field experiments as the basic parameter of the model. The Hasofer-Lind Method is adopted to solve the reliability and the risk probability of vehicle skidding. The results show that in the traffic characteristics, the AADTT has a significant impact on the pavement friction; When the AADTT on the road exceeds 2000 veh/d, the increasing CTV leads to friction decrease rapidly and therefore has a significant impact on the risk of horizontal curve. Especially for roads with more than 50 million vehicles of the CTV, the risk of the horizontal curve shows a sharp increase with CTV rising. The research results can provide reference for the road maintenance department to determine the timing of road maintenance., Competing Interests: The authors declare that they have no conflicts of interest.

The design hourly volume (DHV) of traffic based on the 30th highest hourly volume (30 HV) of the year has been widely applied in expressway design in various countries to balance the benefit and economy of expressway engineering. However, this design method has barely changed since it was first adopted in China, which may be contrary to the rapidly changing traffic macroenvironment. In this study, annual hourly traffic volume (HV) data pertaining to expressways in East China, Southwest China and Northwest China were collected. Based on the descending order of the obtained HV and HV factor data, the distribution patterns of the traffic demand throughout the year and peak hours were analyzed. The distribution characteristics of the HV, typicality of 30 HV and applicability of the DHV factor were investigated. It was found that severe polarization occurred in the HV distribution in China. The actual 30 HV factor is more than 0.5 times the recommended value in the specification. Continued use of the current DHV would result in more than 200 h of inefficient travel time, 5.7 times more than expected, with the DHV factor is currently no longer applicable in China. Furthermore, the annual 30 HV value loses its typical status. Depending on the level of local economic development, using 10 HV factor or 80 HV factor as the new DHV factor can better alleviate the congestion problem. This study determines the reasons for the widespread congestion issues in China from the perspective of expressway design, which is beneficial to adjust the basis of expressway design in China.

Blood-Brain Barrier (BBB) is one of the most important physiological barriers strictly restricting the substance exchange between blood and brain tissues. While the BBB protects the brain from infections and toxins and maintains brain homeostasis, it is also recognized as the main obstacle to the penetration of therapeutics and imaging agents into the brain. Due to high specificity and affinity, peptides are frequently exploited to decorate nanocarriers across the BBB for diagnosis and/or therapy purposes. However, there are still some challenges that restrict their clinical application, such as stability, safety and immunocompatibility. In this review, we summarize the biological and pathophysiological characteristics of the BBB, strategies across the BBB, and recent progress on peptide decorated nanocarriers for brain diseases diagnosis and therapy. The challenges and opportunities for their translation are also discussed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

According to recent research, the COVID-19 pandemic has impacted road traffic quality. This study aims to analyze the impacts of COVID-19 travel restriction policies on the traffic quality of the national and provincial trunk highway network (NPTHN) in Shaanxi Province. We collected the traffic data of the NPTHN for three consecutive years (from 2019 to 2021), before and after the COVID-19 outbreak, including weekly average daily traffic, weekly traffic interruption times, weekly traffic control time, weekly traffic accidents, weekly traffic injuries, and weekly traffic deaths. Using descriptive statistics and dynamic analysis methods, we studied the safety and service levels of the NPTHN. We set up an assessment model of the NPTHN operational orderliness through dissipative structure theory and entropy theory to study the operational orderliness of the NPTHN. Results show that in 2020, the service level, safety level, and operational orderliness of the NPTHN dropped to the lowest levels. The pandemic was gradually brought under control, and the travel restriction policies were gradually reduced and lifted. The adverse impacts on the operational orderliness of the NPTHN decreased, but the operational orderliness did not yet recover to the pre-pandemic level. Meanwhile, the service and safety levels of the NPTHN did not recover. Taken together, the COVID-19 travel restriction policies had adverse impacts on the traffic quality of the NPTHN in Shaanxi Province.

The robust attachment of particles at fluid interfaces is favorable for engineering new materials due to the large capillary energy, but it meets significant challenges when particle removal is a requirement. A previous study has shown that soap films can be utilized to achieve particle separation from liquid marbles. Here, we investigate the effects of particle size on the particle separation from liquid marbles using fast dynamics of drop impact on a soap film. Experimental observations disclose that the fast dynamics of the liquid marble involves coalescence, bouncing, stripping, or tunneling through the film by controlling the falling height and drop volume. More importantly, the active regime of the stripping mode can be selective-controlled by tuning the particle size, and the smaller stabilizing particles make a wider stripping regime. This is attributed to the smaller change of the surface energy resulting from the larger surface tension of LMs wrapped by smaller particles. Theoretical analysis reveals that the stripping thresholds are determined by the energy competition between kinetic energy, the increased surface energy and viscous dissipation, which offers important insights into particle separation by tuning the particle size. The present study provides guidelines for applications that involve phase separation.

The aim of this study was to quantify the effect of radius over horizontal curve sections on driving workload ( DW ). Twenty-five participants participated in the driving simulation experiments and completed five driving scenes. The NASA-TLX scale was used to measure the mental demand, physical demand, and temporal demand in various scenes, which were applied to assess subjective workload ( SW ). Objective workload ( OW ) assessment methods were divided into three types, in which the eye tracker was used to measure the blink frequency and pupil diameter, and the electrocardiograph (ECG) was used to measure the heart rate and the heart rate variability. Additionally, the simulator was used to measure the lateral position and the steering wheel angle. The results indicate that radius is negatively correlated with DW and SW , and the SW in a radius of 300 m is approximately twice that in a radius of 550 m. Compared with the ECG, the explanatory power of the OW can be increased to 0.974 by combining eye-movement, ECG, and driving performance. Moreover, the main source of the DW is the maneuver stage, which accounts for more than 50%. When the radius is over 550 m, the DW shows few differences in the maneuver stage. These findings may provide new avenues of research to harness the role of DW s in optimizing traffic safety.

Owing to the complicated geometric conditions and increasingly diversified driving environment, freeway curves have become a road section with frequent serious accidents. To ensure safe driving on curves, drivers must first perceive the movement condition and the vehicle's position, and accurately evaluate the characteristics of the road to make the right speed choice. In this process, the perception of speed plays a crucial role. The present study aims to investigate the driver's speed perception characteristics with respect to freeway curves to better understand the driver speed selection mechanism. We first construct six three-dimensional (3D) virtual highway models, which are consistent with the geometric lines and traffic engineering instruments of real freeways. A virtual simulation test is then conducted in a highly immersive environment. After the completion of the simulation experiment, we conduct a field verification experiment, test the actual driving speed and perceived speed of drivers in the same place as the simulation experiment, and verify the effectiveness of the simulation method. Finally, 25 3D curve models of four different types are constructed, and the influence of curve characteristics (e.g., curve radius, curve combination, tangent length between curves) on drivers' speed perception accuracy are tested on the simulation platform. The results show that the driver's perceived speed is lower than the real speed when driving on curves, and the tangent-to-spiral (TS) point is the section where the driver's speed is most underestimated. Radius was the most important factor affecting driver's speed perception, but the tangent length between curves also had a lesser influence. However, the curve combination had no effect on it. Our findings can help researchers and road designers understand the reasons for drivers' speed choice, thus promoting drivers' safety on freeway curves., Competing Interests: The authors have declared that no competing interests exist.

This study assessed the activity and community structure in different types of sludge to reveal the partition mechanism of anammox and nitrifiers in a full-scale partial nitrification-anammox plant. Batch experiments confirmed that suspended sludge had higher partial nitrification capacity, and biofilm sludge had higher anammox activity, 16.9 times higher than suspended sludge. qPCR analysis confirmed that the amoA gene was mainly present in suspended sludge, and the highest abundance of the Amx gene was observed in biofilm sludge, reaching 1.01 × 10 7 copies/ng DNA. High-throughput results revealed that Nitrosomonas was the main ammonia-oxidizing bacteria with high activity in suspended sludge, and Candidatus Brocadia had the highest abundance of 13.4% in biofilm sludge. This is the exploration of the microbial community of three different sludge types in the full-scale sidestream PN/A system for the first time, which can guide the construction and replication of full-scale PN/A plants., Competing Interests: QC was employed by the Shandong Electric Power Engineering Consulting Institute Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xu, Cui, Bu, Ismail and Ni.)

Aggressive driving behaviors due to drivers' underestimation of risks are one of the major causes of traffic accidents. Due to the complexity of factors influencing risk perception, the mechanism of risk underestimation remains unclear. In this study, the theory of planned behavior (TPB) was extended by adding a new variable, namely drivers' normlessness, forming an extended TPB (ETPB) framework to analyze the factors influencing risk underestimation and the extent of their influence. A total of 376 drivers' perceived characteristics of risk underestimation were collected through an online survey, and a structural equation model was applied to investigate the effects of normlessness, behavioral attitudes, subjective norm, and perceived behavioral control on the tendency to underestimate the risk. The results showed that the ETPB model can explain the variance in the underestimation risk behavior by 69%; perceptual behavior control, attitude, and subjective norm (in descending order) had significant positive effects on driver's tendency to underestimate risk; the normlessness variable can directly promote attitude and underestimated risk behavior; drivers with low annual mileage, complete insurance coverage, and no prior accident experience were more likely to underestimate driving risk. The study contributes to understanding of risk perception characteristics and provide theoretical basis for reducing underestimated risk behavior.

Particle separation from fluid interfaces is one of the major challenges due to the large capillary energy associated with particle adsorption. Previous approaches rely on physicochemical modification or tuning the electrostatic action. Here, we show experimentally that particle separation can be achieved by fast dynamics of drop impact on soap films. When a droplet wrapped with particles (liquid marble) collides with a soap film, it undergoes bouncing and coalescence, stripping and viscous separation, or tunneling through the film. Despite the violence of splashing events, the process robustly yields the stripping in a tunable range. This viscous separation is supported by the transfer front of dynamic contact among the film, particle crust, and drop and can be well controlled in a deterministic manner by selectable impact parameters. By extensive experiments, together with thermodynamic analysis, we disclose that the separation thresholds depend on the energy competition between the kinetic energy, the increased surface energy, and the viscous dissipation. The mechanical cracking of the particle crust arises from the complex coupling between interfacial stress and viscous forces. This study is of potential benefit in soft matter research and also permits the study of a drop with colloid and surface chemistry.

Truck rollover crashes on horizontal curves have been recognized as one of the most serious types of crashes. Driver's instantaneous emergency steering maneuvers (DIESM) play an important role in truck rollover crashes, but have not received much attention. In the present study, the radius of curvature of the actual vehicle travel path (AVTP) under DIESM was calculated based on the transient bicycle model. Rollover margins were used to evaluate the truck-rollover potential under DIESM. To calculate rollover margins, the lateral acceleration under DIESM was calculated based on the radius of the curvature of the AVTP. A rollover threshold formula was introduced to calculate vehicle's rollover thresholds by distinguishing two turning conditions. According to rollover margins, the maximum safe instantaneous input of the steering wheel against rollover for trucks was obtained. Moreover, theoretical results were verified by computer simulation. Results showed: (1) The maximum safe instantaneous inputs of the steering wheel were 259°, 212°, 182°, 162°and 147°, respectively, at speeds of 60 km/h, 70 km/h, 80 km, 90 km and 100 km when the superelevation rate was 0, and (2) superelevation significantly affected truck-rollover potential; the worst turning condition was turning from the inside to the outside of the curve. Due to the consideration of the wheelbase, the centroid position, the tire's cornering stiffness and the suspension roll gain, the prediction results were more accurate.

Icy bridge deck in winter has tremendous consequences for expressway traffic safety, which is closely related to the bridge pavement temperature. In this paper, the critical meteorological conditions of icy bridge deck were predicted by multiple linear regression and BP neural network respectively. Firstly, the main parameters affecting the bridge pavement temperature were determined by Pearson partial correlation analysis based on the three-year winter meteorological data of the traffic meteorological monitoring station on the bridge in Shandong province. Secondly, the bridge pavement temperature is selected as the dependent variable, while air temperature, wind speed, relative humidity, dew point temperature, wet bulb temperature and wind cold temperature were selected as independent variables, and the bridge pavement temperature prediction models of linear regression and 5-layer hidden layer classical BP neural network regression were established respectively based on whether the variables are linear or not. Finally, the prediction accuracy of the above models was compared by using the measured data. The results show that the linear regression model could be established only with air temperature, relative humidity and wind speed, owing to collinearity problem. Compared with multiple linear regression model, the predicted value of the BP neural network has a higher degree of fitting with the measured data, and the coefficient of determination reaches 0.7929. Using multiple linear regression and BP neural network, the critical meteorological conditions of bridge deck icing in winter can be effectively predicted even when the sample size is insufficient., Competing Interests: The authors have declared that no competing interests exist.

Under adverse weather conditions, visibility and the available pavement friction are reduced. The improper selection of speed on curved road sections leads to an unreasonable distribution of longitudinal and lateral friction, which is likely to cause rear-end collisions and lateral instability accidents. This study considers the combined braking and turning maneuvers to obtain the permitted vehicle speed under rainy conditions. First, a braking distance computation model was established by simplifying the relationship curve between brake pedal force, vehicle braking deceleration, and braking time. Different from the visibility commonly used in the meteorological field, this paper defines "driver's sight distance based on real road scenarios" as a threshold to measure the longitudinal safety of the vehicle. Furthermore, the lateral friction and rollover margin is defined to characterize the vehicle's lateral stability. The corresponding relationship between rainfall intensity-water film thickness-road friction is established to better predict the safe speed based on the information issued by the weather station. It should be noted that since the road friction factor of the wet pavement not only determined the safe vehicle speed but also be determined by the vehicle speed, so we adopt Ferrari's method to solve the quartic equation about permitted vehicle speed. Finally, the braking and turning maneuvers are considered comprehensively based on the principle of friction ellipse. The results of the TruckSim simulation show that for a single-unit truck, running at the computed permitted speed, both lateral and longitudinal stability meet the requirements. The proposed permitted vehicle speed model on horizontal curves can provide driving guidance for drivers on curves under rainy weather or as a decision-making basis for road managers., Competing Interests: The authors have declared that no competing interests exist. There are no patents, products in development or marketed products association with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Defensins are a family of cationic antimicrobial peptides active against a broad range of infectious microbes including bacteria, viruses and fungi, playing important roles as innate effectors and immune modulators in immunological control of microbial infection. Their antibacterial properties and unique mechanisms of action have garnered considerable interest in developing defensins into a novel class of natural antibiotic peptides to fend off pathogenic infection by bacteria, particularly those resistant to conventional antibiotics. However, serious pharmacological and technical obstacles, some of which are unique to defensins and others are common to peptide drugs in general, have hindered the development and clinical translation of defensins as anti-infective therapeutics. To overcome them, several technologies have been developed, aiming for improved functionality, prolonged circulation time, enhanced proteolytic stability and bioavailability, and efficient and controlled delivery and release of defensins to the site of infection. Additional challenges include the alleviation of potential toxicity of defensins and their cost-effective manufacturing. In this review, we briefly introduce defensin biology, focus on various transforming strategies and practical techniques developed for defensins and their derivatives as antibacterial therapeutics, and conclude with a summation of future challenges and possible solutions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Iron deficiency anemia (IDA) in pregnant women was associated with increased risks of both maternal and neonatal adverse outcomes. This study aimed to investigate the prevalence of IDA and identify the associated factors of IDA among pregnancy woman in Fuyang, China. The cross-sectional study was carried out in 789 pregnant women using simple random sampling method living in Fuyang, China from August 2017 to May 2018. Overall, the prevalence of IDA was 39.8%. 1-unit increment in maternal age was associated with a 5% increased risk of IDA, and 1-unit increased in BMI was associated with a 6% decreased risk of IDA (all P < .01). When compared with exercise for <30 minutes, 30-60 minutes of daily exercise was associated with a lower risk of IDA ( P = .02). Similarly, when compared with a low frequency intake of iron-rich food, intake≥once/week was associated with a lower risk of IDA ( P < .0001). However, vitamin C-rich food intake ≥twice/day was associated with a higher risk of IDA ( P = .01) and a normal or bad appetite increased the risk of IDA when compared with a good appetite ( P < .01). Our findings suggested that high frequency of iron-rich food intake, good appetite, and moderate physical activity were important for the prevention of IDA during pregnancy.

Truck rollover is a problem that seriously endangers the safety of human life. Under special conditions, when the driver takes a sharp turn, the truck is most prone to rollover. Speed seriously affects the driving stability of the truck in a sharp turn, but the calculation of the safe speed is not accurate enough at present. The aim of this paper is to develop a more accurate safe speed calculation method to avoid the truck rollover in a sharp turn. Firstly, the calculation formula of the rollover threshold was derived based on a theoretical model, then, the simulation tests were carried out. We selected a 4-axle truck with a total weight of 30t as the subject, simulated the dynamic process of the truck rollover in a sharp turn with TruckSim, evaluated the dynamic rollover risk levels of the truck during this process, and verified the accuracy of the simulation results by results of the theoretical model. Finally, by analyzing the steering principle of the vehicle, the safe speed threshold and the limit speed threshold of the truck in a sharp turn were calculated according to the lateral acceleration corresponding to the rollover risk levels. The results show that no matter what the loading condition of the truck is, when the rollover margin is reduced to about 0.15g, the truck just reaches the risk level of critical rollover; the result provides an accurate algorithm for speed thresholds of the truck when turning radius is less than 250 m. The research provides a calculation method for safe speed of trucks from a dynamic perspective. The research results can be applied to the speed warning system of trucks, which can make drivers better control the rollover risk of trucks in the process of driving and improve driving safety., Competing Interests: The authors have declared that no competing interests exist. There are no patents, products in development or marketed products association with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

The water film depth is a key variable that affects traffic safety under rainfall conditions. According to the Federal Highway Administration, approximately 5700 people are killed and more than 544 700 people are injured in crashes on wet pavements annually. While several studies have attempted to address water film depth issues by establishing prediction models, a few focused on the relationship among road geometric features, capacity of drainage facilities and water film depth. To ascertain the influence of the geometric features of road and facility drainage capacities on the water film depth, the road geometry features were first classified into four types, and the facility drainage capacities were considered from three aspects in this study. Furthermore, the concept of short-time rainfall grade was proposed according to the results of the field test. Finally, the theoretical prediction model for the water film depth was conceived, based on the geometric features of road and facility drainage capacities with different rainfall intensities. Compared with the traditional regression prediction models, the theoretical prediction model clearly shows the effects of the geometric features of road and facility drainage capacities. When the road drainage facilities have no drainage capacity, the water film depth increases rapidly with the rainfall intensity. This model can be used to predict the water film depth of road surfaces on rainy days, evaluate the effect of rainfall on the driving environment, and provide guidance for determining safety control measures on rainy days., Competing Interests: The authors have declared that no competing interests exist.

Pseudoboiling in supercritical fluid (SF) has been paid great attention in recent years. Available works mainly focus on thermodynamics analysis. Fewer studies were reported on the spatial time phase distribution. Here, SF is investigated in a multiphase fluid framework using molecular dynamics (MD) simulations. A simulation box contains 10 976 argon atoms, with periodic boundary conditions applied on all the box surfaces. Pressure and temperature are well controlled. Based on MD simulation results, an onset pseudoboiling temperature T^{-} and a termination pseudoboiling temperature T^{+} are defined using the neighboring molecules method, the radial distribution function method, and the two-body excess entropy method. The two transition temperatures divide the whole phase diagram into three regimes of liquidlike, two-phase-like (TPL), and gaslike, and the MD determined T^{-} and T^{+} well matched the thermodynamics-determined values. In the TPL regime, nanovoids are observed to have two distinct characteristics: (1) Particles are sparsely distributed to have gas density inside the void, but are densely populated to have liquid density outside the void. (2) Voids have a curved interface. These characteristics are very similar to bubble characteristics in subcritical pressure. Hence, voids in the supercritical state are called "bubblelike" in this paper. Nonlinear dynamics demonstrates chaotic behavior in the TPL regime, similar to the two-phase regime in the subcritical domain. The above findings give strong evidence that SF in the TPL regime consists of a mixture of bubblelike voids and surrounding liquids. Our work highlights the multiphase feature of a SF, hence, the well-established multiphase theory in subcritical pressures can be introduced to handle the complex SF.

Removal of oil from water is strongly desired due to environmental pollution, and related studies are mainly limited to the material itself. Here, we propose an oil-water separation device, called a floating well, which includes a container for oil collection and a modified mesh screen for oil separation. The mesh screen is superhydrophilic to oil and superhydrophobic to water. The oil removal experiment was performed in a basin. Under the calm surface condition, the oil collection efficiency is shown to be 42-69%. The inadequate oil collection is explained by the breakdown of a thin oil film above water to form an oil-free area, preventing direct contact between the separator and the oil. Sustained by a wave generator, we are surprised to find that with a low-frequency surface wave, the oil collection efficiency is increased to 98%, and the collection speed reaches 2.5 times that under the calm surface condition. The almost complete collection is due to the sustained contact between the separator and the oil, under which the surface wave continuously drives the oil film toward the separator from elsewhere, thus the oil-free area cannot be formed. Our work presents a new clue for large-scale in situ applications, in which the nature wave energy of river/sea can be the driving force for continuous oil separation and collection.

The contact angle of a nanodroplet on a surface may deviate from that of a macrodroplet on a surface. Even though there are many studies regarding line tension, it is not well understood. In this paper, molecular dynamics simulation is performed for nanodroplets on a concave solid wall. The Lennard-Jones (L-J) potential is directly used or modified to simulate the force interaction between argon atoms and between solid-liquid particles. The initial droplet radius is 4, 5, and 6 nm, respectively. The k coefficient is defined as the ratio of the initial droplet radius with respect to the curvature radius of concave walls, which is in the range of 0-0.9, in which k = 0 refers to a flat surface. We found that indeed the contact angle θ of a nanodroplet on a concave wall deviates from that of a macrodroplet on a flat surface. Contact angles display a two region distribution, in which θ increases with increasing k for k < 0.5 and decreases with increasing k for k > 0.5. The k coefficient influences the droplet morphology. With k in the range of 0-0.9, the vapor-liquid interface is switched from a convex shape to a flat shape and finally reaches a concave shape. The line tension generally behaves in an increasing trend with the increase of k but becomes constant when k is beyond 0.7. The liquid densities, radial distribution functions, and coordination numbers show that the liquid particles are more closely packed with each other with the increase of k . The line tension achieves a positive sign and on the magnitude of 10 -11 N, which has a linear increase with respect to the peak density of the first liquid layer.

Background: Neoadjuvant chemotherapy (NAC) and neoadjuvant chemoradiotherapy (NACR) are the standard treatments for esophageal squamous cell carcinoma (ESCC). However, the 5-year overall survival (OS) rate is still far from satisfactory. In recent years, immune checkpoint inhibitors (ICIs) have shown promising results in the treatment of ESCC. More than 20 phase II clinical trials have been launched to explore combinations of ICIs in the neoadjuvant setting for ESCC. Based on our phase II clinical trial, a two-arm phase III trial was launched in Henan Cancer Hospital. ICIs combined with NAC may usher in a new era and may benefit locally advanced, resectable ESCC patients., Methods: A two-arm phase III trial was launched in April 2020 in Henan Cancer Hospital. Patient recruitment will be completed within 18 months. The primary endpoint is event-free survival (EFS). The secondary endpoints include pathologic complete response (pCR), disease-free survival (DFS) rate, overall response rate (ORR), R0 resection rate, major pathologic response (MPR), adverse events (AEs), complication rate and quality of life (QOL). A biobank of pretreatment, resected tumor tissue and paired blood samples will be built for translational research in the future., Discussion: This RCT directly compares NAC with neoadjuvant toripalimab plus chemotherapy in terms of EFS for locally advanced ESCC. The results may usher in a new era of resectable ESCC treatment., Trial Registration: NCT04280822 (https://www.clinicaltrials.gov/ct2/show/NCT04280822). Registered title: "A Phase III, Randomized Controlled Study of Neo-adjuvant Toripalimab (JS001) in Combination with Chemotherapy versus Neo-adjuvant Chemotherapy for Resectable Esophageal Squamous Cell Carcinoma". Version 1.0/Nov. 21, 2019., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-5404). The authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

Organic Rankine cycle (ORC) power generation is an effective way to convert medium and low temperature heat into high-grade electricity. In this paper, the subcritical saturated organic Rankine cycle system with a heat source temperature of 100~150 °C is studied with four different organic working fluids. The variations of the exergy efficiencies for the single-stage/two-stage systems, heaters, and condensers with the heat source temperature are analyzed. Based on the condition when the exergy efficiency is maximized for the two-stage system, the effects of the mass split ratio of the geothermal fluid flowing into the preheaters and the exergy efficiency of the heater are studied. The main conclusions include: The exergy efficiency of the two-stage system is affected by the evaporation temperatures of the organic working fluid in both the high temperature and low temperature cycles and has a maximum value. Under the same heat sink and heat source parameters, the exergy efficiency of the two-stage system is larger than that of the single-stage system. For example, when the heat source temperature is 130 °C, the exergy efficiency of the two-stage system is increased by 9.4% compared with the single-stage system. For the two-stage system, analysis of the four organic working fluids shows that R600a has the highest exergy efficiency, although R600a is only suitable for heat source temperature below 140 °C, while other working fluids can be used in systems with higher heat source temperatures. The mass split ratio of the fluid in the preheaters of the two-stage system depends on the working fluid and the heat source temperature. As the heat source temperature increases, the range of the split ratio becomes narrower, and the curves are in the shape of an isosceles triangle. Therefore, different working fluids are suitable for different heat source temperatures, and appropriate working fluid and split ratio should be determined based on the heat source parameters.

The entrance and exit sections of a tunnel are the accident black-spots in an expressway. For a safe operation of road tunnels, it is necessary to understand a driver's physiological indices and driving performance when driving through tunnels. In this study, the UC-Win/Road simulation software was used to build 12 tunnel models of different lengths. A simulated driving experiment was carried out in a 6-DoF motion platform. The lateral position of vehicles characterizing the driving performance was measured using the motion platform. Electrocardiogram and eye movement data of 25 recruited drivers were collected simultaneously through the experiment. The spatial changes in a driver's heart rate (HR) growth rate, RMSSD, pupil diameter growth rate and vehicle lateral deviation within 300 m before and after the tunnel entrance and exit were analyzed to determine the variation rules in the different tunnels. The study identified the length range in the tunnel entrance and exit sections that influences the drivers. A quantitative analysis was further carried out to analyze the relationship between the physiological indices and the driving performance indicator. The results showed that a driver's heart rate fluctuates significantly 250 m before the tunnel entrance and 50 m before the exit. In this region, the pupil diameter increases gradually, and drivers tend to shift the vehicle to the left. At the tunnel exit, the HR and RMSSD are affected significantly by the tunnel length, and the variation is higher in longer tunnels. In comparison, the tunnel length has no significant effect on the physiological indicators and driving performance of the drivers at the entrance and exit., Competing Interests: The authors have read the journal’s policy and the authors of this manuscript have the following competing interests: KY is a paid employee of China Railway First Survey and Design Institute Group Company Limited. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketing products to declare.

Extracellular vesicles (EVs) are receiving increasing attention in recent years in the field of cancer treatment. EVs contain specific contents closely related to their donor cells, such as miRNAs, proteins and dsDNAs. As endogenous vesicles, EVs naturally have the characteristics of low toxicity and low immunogenicity and can stably pass through the circulatory system to reach the recipient cells, which make them good carriers to deliver therapeutic agents such as nucleic acid sequences and chemotherapeutics. In many preclinical studies and clinical trials, EVs have demonstrated their unlimited advantages in the field of cancer therapy. However, there are still some challenges that restrict their clinical application, such as yield, heterogeneity, safety, and specificity. In this review, we will focus on the latest breakthrough of EVs in the field of cancer treatment and discuss the challenges in the clinical translation of EVs.

The condensate flooding during dropwise condensation causes serious deterioration in heat transfer performance. In this study, the three-dimensional large-scale molecular dynamics simulation is carried out to investigate the droplet state transition from local flooding mode to Wenzel or from Wenzel to Cassie due to the droplet coalescence under the effect of nanostructure size. In particular, the effect of nanostructure breakage on droplet nucleation and growth is discussed to reveal the mechanism of dropwise condensation heat transfer deterioration. As a potential solution, the lubricant-impregnated surface is proposed to recover the preferred Cassie state by regulating the dynamic wetting characteristics of droplets, and thus the detrimental effect of nanostructure breakage could be effectively avoided.

Radiation pressure refers to the momentum transfer of photons during light "particles" impacting a surface. The force is too small to drive microengines. Different from the classical radiation pressure, the indirect radiation pressure (F m ) is introduced, coming from the momentum change of light-induced bubble expansion. F m is shown to obey F m ∼ (I·r b ) 2 , behaving faster growth of indirect radiation pressure versus light intensity I and bubble radius r b . An effective bubble size range is identified for F m to suppress other forces for bubble in liquid. The top laser irradiation on nanofluid is used in this experiment. A well-defined bubble pulsating flow, being a new principle of bubble piston engine, is demonstrated. During pulse on (≈ns scale), F m exceeding other forces generates an extremely large acceleration, which is three to four orders larger than the gravity acceleration, propelling the bubble traveling downward. During pulse off, the bubble is floating upward due to the nonexistence of F m . In such a way, the piston engine sustains the oscillating ranges of 38-347 µm for bubble diameters and 2.7-457.9 µm for traveling distances of piston. This work is useful to manipulate bubble dynamics in solar energy systems, and can find various applications in optofluidics., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Carbon emissions are the primary reason that contributes to global warming. The gradient has a significant impact on the carbon dioxide (CO2) emissions produced by trucks. The aim of the current paper is to propose a carbon emission quantification model for diesel trucks on longitudinal slope sections and investigate the influence of gradient on the carbon emissions of trucks for use in the low-carbon highway design. The law of conservation of mechanical energy, the first law of thermodynamics, and the vehicle longitudinal dynamics theory were adopted for deriving the carbon emission model of the trucks on the flat, uphill, downhill and round-trip longitudinal slope segments. Three kinds of common trucks were chosen to conduct the field test. Following the test data, the model demonstrates a high accuracy. The minimum gradient which is expected to impact carbon emissions of trucks on the round-trip longitudinal slope sections was the balance gradient as revealed. The gradient of the longitudinal slope is required to be avoided to be greater in comparison with the balance gradient for the achievement of the two-way traffic low carbon operation on a highway. The results of this study are valuable to researchers interested in low carbon road design and low carbon transportation control., Competing Interests: The authors have declared that no competing interests exist.

Sessile droplet evaporation is widely encountered in nature, and it has numerous applications in industrial and scientific communities; therefore, the accurate prediction of droplet evaporation has great significance in practical applications. In this paper, for the first time, a comprehensive theoretical model is built up for diffusion-controlled heat and mass transfer for sessile droplet evaporation on a curved substrate in toroidal coordinates. The evaporative mass transfer is coupled with the heat transfer across the gas-liquid droplet interface, as well as the heat transfer across the solid-liquid interface of the curved substrate. The effects of interfacial cooling and thermal conductivity of the droplet and substrate as well as their initial shapes on the droplet evaporation are provided in details. It is found that the evaporative flux usually increases sharply near the droplet edge due to the short distance for heat conduction from the substrate to the droplet; however, it can be reversed from sharp increasing to decreasing at a low thermal conductivity ratio k R < 0.3 of the substrate over droplet or large initial droplet contact angle θ > 30°. The interfacial evaporative cooling effect can always suppress the droplet evaporation. The lifetime of evaporative droplet can be prolonged with the decreasing thermal conductivity ratio, increasing evaporative cooling number, and increasing initial droplet contact angle or tangential angle of a curved substrate. These findings may be of great significance in the applications of droplet evaporation on the curved substrate.

Development of renewable and clean energy as well as bio-based fine chemicals technologies are the keys to overcome the problems such as fossil depletion, global warming, and environment pollution. To date, cultivation of microalgae using wastewater is regarded as a promising approach for simultaneous nutrients bioremediation and biofuels production due to their high photosynthesis efficiency and environmental benefits. However, the efficiency of nutrients removal and biomass production strongly depends on wastewater properties and microalgae species. Moreover, the high production cost is still the largest limitation to the commercialization of microalgae biofuels. In this review paper, the state-of-the-art algae species employed in livestock farm wastes have been summarized. Further, microalgae cultivation systems and impact factors in livestock wastewater to microalgae growth have been thoroughly discussed. In addition, technologies reported for microalgal biomass harvesting and CO 2 mass transfer enhancement in the coupling process were presented and discussed. Finally, this article discusses the potential benefits and challenges of coupling nutrient bioremediation, CO 2 capture, and microalgal production. Possible engineering measures for cost-effective nutrients removal, carbon fixation, microalgal biofuels and bioproducts production are also proposed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier B.V. All rights reserved.)

With increasing utilization of silver nanomaterials, growing concerns are raised on their deleterious effects to the environment. Once discharged in an aquatic environment, the interactions between silver nanowires (AgNWs) and proteins may significantly affect the environmental behaviors, fate, and toxicities of AgNWs. In the present study, three representative model proteins, including ovalbumin (OVA), bovine serum albumin (BSA), and lysozyme (LYZ), were applied to investigate the impacts of the interactions between proteins and AgNWs on the transformations (oxidative dissolution and sulfidation) of AgNWs in an aquatic environment. Fluorescence spectroscopy and isothermal titration calorimetry analyses indicated that there was very weak interaction between OVA or BSA and AgNWs, but there was a strong interaction between the positively charged LYZ and the negatively charged AgNWs. The presence of LYZ not only reversed the surface charge of AgNWs but also resulted in the breakup of the nanowire structure and increased the reactive surface area. The positively charged surface of AgNWs in the presence of LYZ favored the access of sulfide ions. As a consequence, the kinetics of oxidative dissolution and sulfidation of AgNWs were not affected by OVA and BSA but were significantly facilitated by LYZ. The results shed light on the important roles of electrostatic interactions between AgNWs and proteins, which may have important implications for evaluating the fate and effects of silver nanomaterials in complicated environments.

Context: Gonadotropin-releasing hormone analogues (GnRHa) and recombinant human growth hormone (rhGH) have been widely used to treat idiopathic central precocious puberty (CPP) or early and fast puberty (EFP). However, large-scale studies to evaluate the treatment effects on final adult height (FAH) are still lacking., Objective: To assess the effects of long-term treatment for CPP/EFP on FAH and its main influencing factors., Design and Setting: Retrospective, multicenter observational study from 1998 to 2017., Participants: Four hundred forty-eight Chinese girls with CPP/EFP received GnRHa and rhGH treatment (n = 118), GnRHa alone (n = 276), or no treatment (n = 54)., Main Outcome Measures: FAH, target height (Tht), and predictive adult height (PAH)., Results: The height gain (FAH-PAH) was significantly different among the GnRHa and rhGH treatment, GnRHa alone, and no treatment groups (P < 0.05; 9.51 ± 0.53, 8.07 ± 0.37, and 6.44 ± 0.91 cm, respectively). The genetic height gain (FAH-Tht) was 4.0 ± 0.5 cm for the GnRHa + rhGH group and 2.0 ± 0.27 cm for the GnRHa group, while the control group reached their Tht. In addition, 5 critical parameters derived from PAH, bone age, and Tht, showed excellent performance in predicting which patients could gain ≥5 cm (FAH-PAH), and this was further validated using an independent study., Conclusions: The overall beneficial effect of GnRHa + rhGH or GnRHa on FAH was significant. The control group also reached their genetic target height. Clinicians are recommended to consider both the potential gains in height and the cost of medication., (© Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Driven by nanoparticle plasmonic heating, sessile droplet evaporation presents challenges on the coupling mechanisms between time-spatial heat source distribution and flow/temperature fields in a droplet. Here, symmetric/asymmetric solar-driven droplet evaporation is investigated. An infrared camera captures droplet surface temperatures in the micrometer scale after correction. An optical three-dimensional profiler quantifies nanoparticle deposition in the nanoscale. We show that droplet surface temperatures do display a nonmonotonic variation trend. Based on measurements, we are able to decouple the droplet into a contact line region (CLR) and a bulk volume region (BVR). The CLR volume is two to three magnitudes smaller than the droplet volume. The temperature gradient is significant in CLR, but flat temperature exists in BVR. Radial flow in BVR transports nanoparticles from the droplet body to the contact line, while Marangoni flow in CLR stabilizes nanoparticles there. Light energy is also decoupled based on its wavelength band. It is found that CLR dominates the visible energy absorption, but BVR has a weak contribution. Top light heating causes symmetry temperatures and a coffee-ring profile along the circumference. However, side heating yields higher temperatures and more nanoparticles deposition on the sunny side than on the night side. The above findings are valid when the initial droplet volume and incident irradiation flux are changed on the hydrophilic wall. The hydrophilic wall and hydrophobic wall maintain the evaporation modes of constant contact diameter and "stick-slip", respectively. The present paper enhances the understanding of light-induced droplet evaporation from the multiscale point of view.

It is great significance to understand the mechanism of heat transfer deterioration of supercritical CO 2 for heat exchanger design and safe operation in the supercritical CO 2 Brayton cycle. Three-dimensional steady-state numerical simulation was performed to investigate the behavior of supercritical CO 2 heat transfer in heated vertical up-flow tube with inner diameter d i = 10 mm and heated length L h = 2000 mm. Based on the characteristics of inverted-annular film boiling at subcritical pressure, the heat transfer model of supercritical CO 2 flowing in the heated vertical tube was established in this paper. The mechanisms of heat transfer deterioration (HTD) and heat transfer recovery (HTR) for supercritical CO 2 were discussed. Numerical results demonstrate that HTD is affected by multiple factors, such as the thickness and property of vapor-like film near the wall, the turbulence intensity near the interface between liquid-like and vapor-like, and in the liquid-like core region as well as the distribution of radial velocity vector. Among the above factors, the change of turbulent kinetic energy caused by the buoyancy effect seems to be a more important contributor to HTD and HTR. Furthermore, the influences of heat flux and mass flux on the distribution of wall temperature were analyzed, respectively. The reasons for the difference in wall temperature at different heat fluxes and mass fluxes were explained by capturing detailed thermal physical properties and turbulence fields. The present investigation can provide valuable information for the design optimization and safe operation of a supercritical CO 2 heat exchanger.

Silver nanowires (AgNWs) are widely produced in many electronic and optical products, and could be inevitably discharged into the aquatic environments. Sulfidation is one of the most important transformation processes of AgNWs, and could significantly affect their fate and interactions with other pollutants in aquatic environment. In the present study, the sulfidation products of AgNWs with different atomic ratio of Ag and S were prepared under environmentally relevant conditions. The crystal structure, elemental composition, morphology and size of the sulfidation products were comprehensively characterized by powder X-ray diffraction, UV-vis spectroscopy, X-ray photoelectron spectroscopy and transmission electron microscope. The products were heterostructured nanowires and the Ag 2 S/Ag molar ratio increased with extension of the reaction time. The produced Ag 2 S-Ag nanowires displayed a good photocatalytic activity and facilitated the degradation of the copresent organic pollutant bisphenol A (BPA) under simulated sunlight irradiation. As sulfidation time increased, more Ag 2 S was generated and the Ag 2 S-Ag composites displayed high promotion effect on BPA degradation. This effect could be ascribed to the favorable synergistic effects between Ag 2 S and AgNWs, such as high electron-hole separation efficiency and low charge transfer resistance. The chemical scavenger experiments demonstrated that superoxide anion radicals and photogenerated holes in the sulfidation products of AgNWs could be the main reactive species for photocatalytic degradation., (Copyright © 2019 Elsevier Inc. All rights reserved.)