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In order to study the effect of reflow process parameters on the copper-tin biphase interface structure of hot dip tinned electronic copper strip, heat treatment of C14415 hot dip tinned electronic copper strip was carried out. Electron backscattering diffraction (EBSD) and transmission electron microscopy (TEM) were used to collect and analyze the microcosmic characteristics of the copper-tin biphase interface of hot dip tin-coated electronic copper strip after reflux. The results show that Cu6Sn5 and Cu3Sn are formed at the Cu–Sn biphase interface during reflow welding, and Cu6Sn5 is first formed at the Cu–Sn biphase interface, and Cu3Sn is gradually formed at the bottom of Cu6Sn5 when the Cu–Sn biphase interface forms a high temperature and stable environment. During the growth of Cu and Sn and its series of compounds, different reflow welding processes have no obvious effect on the distribution of interphase orientation difference. The competitive growth process of the multiphase interface during reflow welding was reconstructed through the distribution state of the multiphase interface under different reflow welding processes. The optimal process parameters of reflow welding were 290°C-heat preservation for 3min-air cooling.

As the grade of copper concentrate decreases and its composition becomes increasingly complex, the silver content in the anode plate casting after fire refining increases. This leads to a high silver content in the copper cathode during electrorefining and a substantial loss of precious metals. This study investigated the effect of 1-aminopropyl-3-methylimidazolium bromide (APMImBr) ionic liquid on the migration of silver during high-silver anode plate electrorefining. The results show that APMImBr is adsorbed on the anode surface by reacting with Ag+ released from the anode to form AgBr precipitates, thereby preventing Ag+ ions from entering the electrolyte. Simultaneously, agglomerates of fine Ag–Se compounds and AgBr particles form, resulting in anode slime particles that are sufficiently large to settle quickly to the bottom of the cell, thus inhibiting fine silver-containing particles from adhering to the cathode. Furthermore, APMImBr adsorbs onto the cathode surface, forming CuBr intermediates and inhibiting Cu2+ electrodeposition. This facilitates the refinement of the surface grains and flattens the copper cathode surface. The Ag content of the cathode decreased continuously as the concentration of APMImBr increased. The Ag content of the cathode decreased by 41.67% from 6.0 ppm (no additives) to 3.5 ppm upon the addition of the optimal concentration of 300 mg/L of APMImBr.

The proton therapy system has significant clinical advantages over traditional tumor radiation treatment equipment and is also far more complex in terms of system architecture. However, due to the large size and complexity of these devices, electromagnetic compatibility testing faces considerable challenges. To address these challenges, this paper studies the electromagnetic characteristics and working principles of various components in the proton therapy system, combines them with corresponding standard requirements, and delves into the difficulties and testing methods of electromagnetic compatibility immunity detection through actual repeated tests. Furthermore, the paper proposes testing key points for beam quality tests and provides references for the selection of emission sources and distance settings in radio frequency electromagnetic field radiation immunity testing. The paper also supplements and improves the descriptions of alternative methods in the standards and offers solutions and testing suggestions for issues such as the excessive thickness of cables in the proton therapy system and the lack of suitable fixtures in conducted anti-interference tests. The provision of these solutions offers more effective references for related staff during testing, helps address difficulties encountered in practical operations, and thus more effectively ensures the safety and effectiveness of proton therapy systems.

ABSTRACT Introduction Divided narratives pose long‐standing difficulties in physician and patient communication. In decision‐making on cancer treatment, divided narratives between physicians and patients hinder mutual understanding and agreement over the illness and its treatment. For effective decision‐making on treatments, it is necessary to investigate the similarities and differences in these divided narratives. Methods This study adopted a qualitative research design of narrative inquiry to examine the data, which included interviews with 32 cancer patients and 16 paired physicians in two hospitals in China. Data analysis was conducted using grounded theory to generate findings. Results Both physicians and patients were concerned about goals and obstacles to their decision‐making on cancer treatment. Four common aspects of goal setting were identified from the divided narratives: decision pools, treatment goals, identity practice and preferred identity. Four common obstacles were identified: pains and trust, communication gap, financial issues and complex family. However, the meanings attached to these eight aspects differed between physicians and patients. Conclusion Cancer treatment decision‐making is an encounter of the scientific world and lifeworld. A divided narrative approach can identify the similarities and differences in the decision‐making on cancer treatment between physicians and patients. Physicians generally adopt a rational decision‐making approach, whereas patients generally adopt a relational decision‐making approach. Despite the common concerns in their goals and obstacles, physicians and patients differed in their contextualized interpretations, which demonstrates the physicians' and the patients' pursuit of preferred identities in decision‐making. The results of this study provide a new perspective to treatment decision‐making, emphasizing the importance of narrative integration in reaching mutual agreement. Patient and Public Contribution The findings were shared with 15 cancer patients and caregivers for feedback and advice in June 2024. This study was also presented at the international conferences of COMET (International and Interdisciplinary Conference on Communication, Medicine, and Ethics) and ICCH (International Conference on Communication in Healthcare) 2023 for continuous feedback and comments.

Raptors can change the shape and area of their wings to an exceptional degree in a fast and efficient manner, surpassing other birds, insects, or bats. Some researchers have focused on the functional properties of muscle skeletons, mechanics, and flapping robot design. However, the wing motion of the birds of prey has not been measured quantitatively, and synthetic bionic wings with morphing abilities similar to raptors are far from reality. Therefore, in the current study, a 3D suspension system for holding bird carcasses was designed and fabricated to fasten the wings of Falco Peregrinus with a series of morphing postures. Subsequently, the wing skeleton of the falcon was scanned during extending motions using the computed tomography (CT) approach to obtain three consecutive poses. Subsequently, the skeleton was reconstructed to identify the contribution of the forelimb bones to the extending/folding motions. Inspired by these findings, we propose a simple mechanical model with four bones to form a wing-morphing mechanism using the proposed pose optimisation method. Finally, a bionic wing mechanism was implemented to imitate the motion of the falcon wing—divided into inner and outer wings with folding and twisting motions. The results show that the proposed four-bar mechanism can track bone motion paths with high fidelity.

This study compared the performance of extracted asphalt and laboratory aged asphalt. The five-year service asphalt mixtures were used for extraction in this study. The laboratory aged asphalt experienced the Rolling thin film oven (RTFO) aging the Pressure aging vessel (PAV) aging with variable duration (5, 10, 15, 20, and 25 hours). By comparing the softening point, viscosity, and rheological properties of both, an aging simulation protocol was established. For laboratory aged asphalt binder, the softening point increases by 3.56 %, 5.68 %, 7.43 %, 8.16 %, and 8.74 % at PAV aging times of 5 h, 10 h, 15 h, 20 h, and 25 h, respectively. The rutting index and viscosity of the aged asphalt gradually increases with the PAV duration. There is a substantial increase in creep recovery rate and a significant decrease in non-recoverable creep compliance for aged asphalt. The rheological aging index demonstrates a linear increasing trend. The sulfoxide (SO) and aromatic (CO) aging indexes of the laboratory-simulated aged asphalt progressively rise with prolonged PAV aging time. The SO and CO aging indexes of the extracted asphalt consistent with RTFO aged asphalt experienced PAV aging 20 and 25 hours. The extracted asphalt can be simulated in the laboratory under standard RTFO conditions and a 22.26 hours PAV duration at a pressure of 2.1 MPa ± 0.1 MPa. This study introduces a methodology for simulating asphalt aging in an authentic service environment by adjusting the laboratory aging test conditions.

The purpose of this study is to further investigate the strength size effect and failure mechanism of asphalt mixtures and clarify the strength parameter conversion relationship between standard and non-standard size samples. The article established an improved microscopic model for uniaxial compression and indirect tensile testing of asphalt mixtures based on laboratory and discrete element simulation tests. The effects of thickness and gradation on the uniaxial compressive strength (UCS) and indirect tensile strength (ITS) of asphalt mixtures were studied. The loading rates of the UCS and ITS tests were set at 2 mm/min and 50 mm/min, respectively. Additionally, the tensile-compressive stress distribution, crack propagation, and strength contribution rates of different contact types within the sample were investigated during the virtual model loading process. The reliability of the model was validated through laboratory test results. Finally, the strength parameter conversion relationship between standard and non-standard size samples was investigated. The study found that the UCS of asphalt mixtures decreases with increasing thickness, while the ITS increases with increasing thickness, with average reduction and increase rates of 70.69 % and 24.18 %, respectively. The contact fracture ratio and the strength contribution rate of the aggregate-asphalt mortar contacts both exceed 50 %, indicating that the fracture of these contacts is the primary cause of asphalt mixture failure. The use of small-sized samples instead of standard samples in practical applications is promising. These research work outcomes can serve as a theoretical basis for designing asphalt pavement materials and acquiring existing asphalt pavement material parameters.

Predicting the strength of asphalt mixtures with different specifications under various conditions was a highly challenging task. The standard strength test lacked consideration of multiple factors, resulting in an inability to accurately characterize the properties of the pavement. This paper proposed a strength prediction approach based on influence factor analysis using the back-propagation neural network (BPNN) and support vector machine (SVM). The strength dataset was processed to realize the physical analysis of factors influencing asphalt mixture strength. Stress state (Direct tensile with250mm×50mm×50mm, Uniaxial compression with 100mm×Φ100mm, Indirect tensile with63.5mm×Φ100mm,Four-point bending with 380mm×63.5mm×50mm), temperatures (35 ̊C, 25 ̊C, 15 ̊C, 0 ̊C, −15 ̊C, −25 ̊C), and load rates (0.02 MPa/s, 0.05 MPa/s, 0.1 MPa/s, 0.5 MPa/s) were selected as input features to train the BPNN and SVM. The strength prediction model for asphalt mixture under complex conditions was established by optimizing the parameters of algorithms. The performance of the BPNN and SVM was evaluated and compared by the root mean square error, determination coefficient, and mean absolute percentage deviation. The results show that the asphalt mixture specimen with different specifications under various stress states presents significant discrepancies. The maximum compressive strength is followed by the bending strength, then comes the indirect tensile strength, and the smallest is the direct tensile strength. The difference in the role of asphalt or aggregate is the main reason for the diversity in strength. The increase in temperature leads to asphalt softening, which reduces the strength of the asphalt mixture. The increased loading rate meant the loading time was short cause the strength increased. In addition, the predictive value of the strength under various conditions was consistent with the results of the experiments. The hidden neurons in the BPNN were set to 9, achieving the prediction accuracy is high (R2=0.99). The penalty coefficient of the SVM was set to 500 and the kernel function parameter was set to 300, resulting in the error within 0.02 %. When comparing the performance metrics of BPNN and SVM, it becomes evident that SVM outperforms BPNN in terms of prediction accuracy. Specifically, SVM exhibits a coefficient of determination of 0.9983, a root mean square error of 0.208, and a mean absolute percentage deviation of 0.145, whereas BPNN demonstrates respective values of 0.9979, 0.233, and 0.067. This study lays a theoretical foundation for the digital and intelligent road construction.

Millions of women worldwide are infertile due to gynecological disorders, including premature ovarian insufficiency, polycystic ovary syndrome, Asherman syndrome, endometrial atrophy, and fallopian tube obstruction. These conditions frequently lead to infertility and have a substantial impact on the quality of life of the affected couples, primarily because of their psychological implications and high financial costs. Recently, using platelets to stimulate cell proliferation and tissue differentiation has emerged as a promising approach in regenerative medicine. Platelet-rich plasma (PRP) shows considerable potential for promoting endometrial hypertrophy and follicle development, making it a promising therapeutic option for tissue repair or replacement. This review provides an overview of the recent advancements and underlying mechanisms of PRP therapy for various female reproductive diseases and presents new therapeutic options for addressing female infertility.

Optimizing the structure of the carbon metabolic network is essential for enhancing network performance. However, a knowledge gap remains in systematically evaluating the network structure and comprehensively identifying the key nodes and paths, particularly in a carbon metabolism system that involves the frequent transition of carbon element across the air, water, and soil mediums. Hence, taking Guangzhou, China, as a case study, we constructed a cross-media metabolism network model based on material flow analysis. Subsequently, the general structural characteristics and key nodes/paths of the network were investigated through the integration of trophic structure analysis, contribution analysis, and stability analysis in ecological network analysis. The results primarily suggest that the connections among nodes in the carbon metabolism network have become looser, and the metabolic system structure was in a medium state with some defects from 2010 to 2020. Sectors of construction and transportation, as well as carbon flows from the agriculture sector to the construction sector and the energy conversion sector to the transportation sector, were identified as the key nodes and paths influencing the structural characteristics. Subsequently, twenty-one optimization scenarios were developed, with the results suggesting the advantage of collaborative regulation of key nodes/paths (e.g., increasing the carbon flows both from the agriculture sector to the construction sector and from the energy conversion sector to the transportation sector by 50%). This work may provide useful guidance for the structure optimization of the carbon metabolism system.

This study normalized the mixture's fatigue behavior at various temperatures, and the strength and fatigue tests of the mixture were conducted. The stress state of the asphalt mixture includes direct tensile, uniaxial compression, and indirect tensile. The Desai yield surface and fatigue path were proposed. And a normalized fatigue characteristics model of the mixture was established. The following conclusions were obtained. With the increases in the loading rate, the strength of the asphalt mixture increased. As the temperature increases, the strength of the mixture is reduced. At various temperatures and rates, the strength forms a closed curved surface. The Desai strength yield surface was established, which forms a closed curved surface. When the loading rate and temperature are below a certain critical line, the asphalt mixture will not undergo strength damage. At a fixed stress state, the fatigue damage path of the mixture was determined. The stress ratio was determined considering the influence of the loading rate. In this way, a normalized model can be described to express the asphalt mixture fatigue properties at various temperatures and stress levels. For the asphalt mixture in an indirect tensile state, the normalized fatigue equation parameter is 4.09. This model is more suitable for reflecting the viscous-elastic behavior of the mixtures than the fatigue equation determined by the notional stress ratio.

In cold regions with high daily temperature gradients (>20 °C), the durability of cement-stabilized macadam (CSM) base materials is poor and prone to cracking. To effectively reduce the cracking of semi-rigid base layers in cold regions with high daily temperature gradients and extend fatigue life, this study focused on cracking and fatigue characteristics of CSM with a 10% commercial early strength agent (ESA) added by the external mixing method under different curing conditions. The ESA was manufactured by Jiangsu Subote New Materials Co., Ltd. (Nanjing, China). The curing conditions were divided into variable temperature (0–20 °C) and standard temperature (20 °C). CSM curing was carried out through a programmable curing box. The research results indicated that the variable temperature curing conditions reduced the strength and fatigue resistance of CSM and accelerated the modulus attenuation rate of CSM. At the same time, the drying shrinkage of CSM was greater. The temperature shrinkage coefficient and strain of CSM under variable temperature conditions were smaller than those under standard temperature conditions. The effect of variable temperature conditions on the cracking and durability of CSM could not be ignored in cold regions. Compared to standard temperature curing conditions, the indirect tensile strength of CSM reduced by 31.04% under variable temperature conditions, the coefficient of variation increased by 2.97 times, and the discrete type significantly increased. Compared with CSM without ESA, the dry and temperature shrinkage strains of CSM with 10% ESA were reduced by 24.65% and 26.10%, respectively. At a stress level of 0.6, compared to standard temperature curing conditions, the fatigue life of CSM decreased by 97.19% under variable temperature conditions. Under variable temperature conditions, the fatigue life of CSM with 10% ESA increased by 196 times compared to 0% ESA. Adding ESA enhanced the anti-shrinkage cracking, strength, and durability of CSM under variable temperatures. ESA incorporation effectively compensated for the weakened characteristics of CSM under variable temperature conditions. The study proposed a practical approach for boosting the durability of CSM in cold environments.

Abstract Although VEGF-B was discovered as a VEGF-A homolog a long time ago, the angiogenic effect of VEGF-B remains poorly understood with limited and diverse findings from different groups. Notwithstanding, drugs that inhibit VEGF-B together with other VEGF family members are being used to treat patients with various neovascular diseases. It is therefore critical to have a better understanding of the angiogenic effect of VEGF-B and the underlying mechanisms. Using comprehensive in vitro and in vivo methods and models, we reveal here for the first time an unexpected and surprising function of VEGF-B as an endogenous inhibitor of angiogenesis by inhibiting the FGF2/FGFR1 pathway when the latter is abundantly expressed. Mechanistically, we unveil that VEGF-B binds to FGFR1, induces FGFR1/VEGFR1 complex formation, and suppresses FGF2-induced Erk activation, and inhibits FGF2-driven angiogenesis and tumor growth. Our work uncovers a previously unrecognized novel function of VEGF-B in tethering the FGF2/FGFR1 pathway. Given the anti-angiogenic nature of VEGF-B under conditions of high FGF2/FGFR1 levels, caution is warranted when modulating VEGF-B activity to treat neovascular diseases.

The modulus is a crucial material parameter reflecting stiffness characteristics of asphalt mixture in the elastic stage. Under specific conditions such as identical temperatures, loading velocities, and stress amplitudes, the moduli under the same stress state are theoretically identical. However, the moduli were artificially divided into dynamic moduli and static moduli based on loading methods during test, which brought uncertainties and disunity for estimating the stiffness performance of asphalt mixture. In this study, the dynamic and static moduli under distinct temperatures, loading velocities, and stress states were measured. The relationship between dynamic and static moduli was established by applying loading velocities as independent variable and moduli as the dependent variable. Through Sigmoidal function and WLF function fitting, the uniform characterization master curves of dynamic and static moduli under distinct temperatures, loading velocities, and stress states were established. The moduli of asphalt mixture under distinct test temperatures, loading velocities, and stress states can be obtained by the models, which provide material parameters for mechanical response analysis of asphalt pavements under distinct service environments. This resolves the issue of inconsistent moduli parameter selection.

The aging degree of reclaimed asphalt pavement (RAP) is complex and diverse, and the current utilization rate of RAP is far from meeting the needs of green cycle development. To explore the effect of Styreneic Methyl Copolymer (SMC) rejuvenator of aging asphalt and the performance of SMC regenerated asphalt mixture containing 50% and 60% RAP, this study used SMC rejuvenator to regenerate SBS-modified asphalt with different aging degrees. The high and low-temperature rheological properties of regenerated asphalt were evaluated by temperature sweep test, multi stress creep recovery test, and bending beam rheometer test. Then, the recommended content of the SMC rejuvenator was obtained by using Matlab to establish the corresponding model. Finally, the road performance of the regenerated mixture with high-content RAP was verified. The test results showed that the recommended content range of the SMC rejuvenator for the aging asphalt with PAV (Pressurized Aging Vessel) 0 h, PAV5h, PAV10h, PAV15h, PAV20h were 1.56∼2.31%, 3.03∼3.36%, 4.269∼4.48%, 5.23∼5.66%, 5.95∼6.91%, respectively. The road performance of the SMC regenerated asphalt mixture with 50% and 60% RAP content met the specification requirements. SMC rejuvenator had no significant negative impact on high-temperature performance, significantly improving low-temperature cracking resistance. SMC regenerator had a positive significance in improving regeneration efficiency.

The objective of this research is to enhance the high-temperature antirutting and antiaging characteristics of bioasphalt. In this study, silica fume (SF) was selected to modify bioasphalt. The dosage of bio-oil in bioasphalt was 5%, and the dosage of SF was 2%, 4%, 6%, 8%, and 10% of bioasphalt. The high- and low-temperature characteristics, aging resistance, and temperature sensitivity of Bio + SF were evaluated by temperature sweep (TS), the multiple stress creep recovery (MSCR) test, the bending beam rheology (BBR) test, and the viscosity test. Meanwhile, the road behavior of the Bio + SF mixture was evaluated using the rutting test, low-temperature bending beam test, freeze–thaw splitting test, and fatigue test. The experimental results showed that the dosage of SF could enhance the high-temperature rutting resistance, aging resistance, and temperature stability of bioasphalt. The higher the dosage of SF, the more significant the enhancement effect. However, incorporating SF weakened bioasphalt’s low-temperature cracking resistance properties. When the SF dosage was less than 8%, the low-temperature cracking resistance of Bio + SF was still superior to that of matrix asphalt. Compared with matrix asphalt mixtures, the dynamic stability, destructive strain, freeze–thaw splitting strength ratio, and fatigue life of 5%Bio + 8%SF mixtures increased by 38.4%, 49.1%, 5.9%, and 68.9%, respectively. This study demonstrates that the development of SF-modified bioasphalt could meet the technical requirements of highway engineering. Using SF and bio-oil could decrease the consumption of natural resources and positively reduce environmental pollution.

Objective To explore the effects of home-based telerehabilitation (TR) on dynamic alterations in regional intrinsic neural activity and degree centrality in stroke patients by resting-state functional MRI (fMRI) methods. Methods The neuroimaging data of 52 stroke patients were analyzed. Dynamic regional spontaneous neural activity (dynamic amplitude of low-frequency fluctuations, dALFF; and dynamic regional homogeneity, dReHo) and dynamic degree centrality (dDC) were compared between the TR and conventional rehabilitation (CR) groups. A flexible factorial model was employed to investigate the expected effects. Results The patients in the TR group showed increased dALFF in the right precuneus and bilateral precentral gyrus (PreCG) and reduced dALFF in the right inferior parietal lobule by the analysis of main effects. Significant differences between groups were detected in the right precuneus, right fusiform gyrus and left middle frontal gyrus for dReHo and in the left cingulate gyrus, right middle temporal gyrus and left precuneus for dDC. A significant correlation was found in the TR group between the changed dALFF in the left PreCG and the changed Fugl-Meyer assessment (FMA) scores from baseline to postrehabilitation. Conclusions This study implied that home-based TR training can alter the patterns of dynamic spontaneous brain activity and functional connectivity in certain brain regions. The identification of key brain regions by neuroimaging indicators such as dynamic regional brain activity and degree centrality in the recovery process would provide a theoretical basis for noninvasive brain stimulation technology and strategies for formulating targeted rehabilitation programs for stroke patients with motor dysfunction.

As a vital component of urban green infrastructures, urban green space (UGS) provides essential ecological, recreational, and social-cultural services to urban residents. Ensuring adequate and equitable accessibility to UGS for all urban residents has become an integral aspect of promoting social justice. However, studies that comprehensively investigate the long-term changes in urban green space accessibility (UGSA) and its equity under rapid urbanization are scarce, thereby limiting the potential guidance for implementing nature-based solutions to enhance ecosystem services that benefit urban residents. In this study, taking Guangzhou, China, as the empirical study area, the UGSA and its equity during 2000–2015 were evaluated at the district level by combining the Gaussian-based two-step floating catchment area method (Gaussian-based 2SFCA) and the Gini coefficient. Meanwhile, the changes in land cover and land use (LULC) were also investigated to reveal the dynamics of the UGS. Moreover, the long-term synchronous changes between UGSA and its equity were explored through a grouping analysis based on the four-quadrant method. The results revealed spatial heterogeneity in UGSA, with peri-urban districts having more accessibility to UGS compared to core-urban districts. The equity of UGSA exhibited an uneven spatial pattern, with most districts displaying consistently low levels of equality. The results of grouping analysis underscored the significance of considering both the improvements of UGSA and its equity in policy-making, leading to specific policy implications for each district. Our study provides valuable insights that can inform future urban spatial greening strategies and contribute to the promotion of sustainable urban development.

Background The association of adverse childhood experiences (ACEs) with chronic disease prevalence among middle-aged and elderly people has become a research hot spot, but the association between ACEs and self-rated health in older people is still unclear, and relevant studies in Chinese population are especially rare. Objective To explore self-rated health in Chinese elderly people, and its association with ACEs. Methods The study was conducted in October 2021. Data about ACEs and self-rated health were acquired by applying from the 2014 and 2018 waves of CHARLS conducted by Peking University, involving 7 579 older people (≥ 60 years old) . The ACEs were stratified into three groups by the times of ACEs events (10 kinds in total) : high-risk (4 or more) , low-risk (1-3) , and reference (zero) . The self-rated health was divided into three levels: good, fair and poor. Ordinal logistic regression was used to analyze the correlation of self-rated health with the number and types of ACEs events. Results Among the participants, the prevalence of good, fair and poor self-rated health was 22.06% (1 672/7 579) , 59.03% (4 474/7 579) , and 18.91% (1 433/7 579) , respectively, and the prevalence of experiencing ≥4, 1-3 and no ACEs events was 25.36% (1 922/7 579) , 69.71% (5 283/7 579) , and 4.93% (374/7 579) , respectively. The self-rated health differed significantly by age, gender, place of living, and types of ACEs (parental divorce, parental violence, parental depression, parental disability, living in an unsafe neighborhood, childhood loneliness, childhood famishment, bullying) (P

Buton rock asphalt (BRA)-modified asphalt has been extensively applied in the pavement because of its excellent aging resistance and high-temperature stability. The research on the overall behavior of BRA-modified asphalt has been relatively comprehensive. However, the main components in rock asphalt contain not only pure asphalt but also a large amount of ash. Their respective roles in asphalt modification still need to be clarified. This study analyzed rock asphalt's morphological changes and dissolution characteristics after heating. Then, the road performance of BRA ash-modified asphalt and BRA-modified asphalt was revealed. Finally, the contribution of pure asphalt and BRA ash to neat asphalt for elevated temperature properties was analyzed quantitatively. The microstructure of BRA and BRA ash was observed. Furthermore, the Fourier transform infrared spectroscopy (FTIR) results of pure asphalt, BRA and BRA-modified asphalt was analyzed. The test consequences demonstrate that the pure asphalt in BRA is not directly compatible with the neat asphalt. The appearance of BRA is soft honeycomb, and pure asphalt is tightly wrapped in mineral particles. BRA is mainly modified by physical miscibility, thus significantly improving the elevated temperature property of neat asphalt. But it will weaken the cryogenic property of neat asphalt. With the increase in BRA content, this effect is more pronounced. Both ash and pure asphalt play a vital role in modifying neat asphalt. With the temperature rise, the weight of ash in conversion gradually increases, and the weight of pure asphalt gradually declines. The weight of ash enhanced with the rise of BRA content, and the weight of pure aspahlt also increased gradually. The average contribution rate of ash to improve the rutting index is 45.57%, and the average contribution rate of neat asphalt to the rutting index advancement is 54.43%.

PurposeThis study aimed to investigate the relationship among changes in corneal topography, retinal vascular density, and retinal thickness in myopic children who underwent orthokeratology for 3 months.MethodThirty children with myopia wore orthokeratology lenses for 3 months. Using optical coherence tomography angiography (OCTA), the retina was imaged as 6 × 6 mm en-face images at baseline and 3 months after orthokeratology. Cornea data was acquired by topography and analyzed by customer MATLAB software. The cornea was divided into 3 zones and 9 sectors. The relative corneal refractive power shift (RCRPS) was used in this study. Changes in retinal vascular density (RVDC) and retinal thickness change (RTC) were associated with RCRPS by using spearman test. Statistical significance was set at p 0.05) were observed at any regions.ConclusionThe correlation between the cornea and the retina was observed after orthokeratology. Cornea changes may affect regional retinal responses accordingly，which may explain how orthokeratology delays myopia progression partially.

ObjectiveThis study aimed to test the inter-examiner and intra-examiner reliability of macular vascular density (VD) measurement of retinal and choriocapillaris plexuses in healthy children using optical coherence tomography angiography (OCTA).Materials and methodsNinety-two school children were prospectively recruited. Macular OCTA images (6 × 6 mm2) were obtained thrice by two examiners using the RTVue-XR Avanti OCT system. The coefficient of variation (COV), intraclass correlation coefficient (ICC), and Bland–Altman plots were used to evaluate the repeatability and reproducibility.ResultsNinety participants aged 6–15 years were enrolled; two participants were excluded because of low-quality images. In the retina, the reproducibility and repeatability of VD became poorer from superficial to deep retinal capillary plexus (superficial: COV = 4.61–11.11%; intermediate: COV = 7.73–14.15%; deep: COV = 14.60–32.28%). For both reproducibility and repeatability, the ICC ranged from moderate to high (superficial plexus: ICC = 0.570–0.976; intermediate plexus: ICC = 0.720–0.968; deep plexus: ICC = 0.628–0.954). In the choroid, the inter-examiner reproducibility and intra-examiner repeatability of the VD measurement of choriocapillaris were excellent in the macula, fovea, parafovea, and perifovea (COV = 1.00–6.10%; ICC = 0.856–0.950). The parameters of the foveal avascular zone (FAZ) also showed significant reproducibility and repeatability (COV = 0.01–0.21%; ICC = 0.743–0.994).ConclusionThe VD measurements of the choriocapillaris and FAZ parameters using OCTA showed excellent inter-examiner and intra-examiner reliability in school children. The reproducibility and repeatability of the VD of three retinal capillary plexuses depended on the depth of the retinal capillary plexus.

Urban flooding can seriously threaten urban ecological security and human life, and therefore urban flood resilience (UFR) is important for urban safety and stability. To comprehensively evaluate urban system performance during the entire process of rainfall, runoff, flooding, and drainage, we developed a systematic framework for UFR assessment covering runoff simulation, flood estimation, and resilience assessment, which broadly corresponded to the phases of resistance, adaptation, and recovery. The UFR in the phases of resistance, adaptation, and recovery was simulated and assessed using a system performance curve (SPC) and technically combining with the hybrid flood model while mainly considering the total simulation time and inundated urban proportion in SPC. Because the extent of urban flooding can be influenced by climate change and the rate of urbanization, we chose the corresponding representative factors of precipitation and infiltration rate and considered 21 simulation scenarios (seven rainfall return periods and three infiltration rates) for which UFR was quantified according to urban system performance. The effectiveness of this framework was demonstrated in application to a typical highly urbanized area (i.e., Dongguan, China). The following results were derived: (1) The inundated area under the pessimistic scenario (i.e., S19) would be nearly four times greater than that under the optimistic scenario (i.e., S3); (2) The values of UFR in Dongguan were 0.9494–0.9863, locating at the high and very high level; (3) The lowest UFR value was 0.6552 in the Shuixiang New City district; and (4) The rainfall return period was the main factor influencing UFR under relatively short rainfall return periods (i.e., S1–S9), while infiltration rate was the principal influencing factor under relatively long rainfall return periods (i.e., S10–S21). The proposed systematic framework could be applied in other cities and large-scale regions like urban agglomerations and provinces.

PurposeTo assess changes in optical quality and visual function in children after 3 months of wearing orthokeratology (OK) lenses.MethodsA total of 25 myopic children aged 8–12 years were recruited and completed the follow-up study. Optical quality, visual function and corneal morphology were assessed at baseline and at follow-ups 1 and 3 months after wearing OK lenses. Optical quality parameters mainly included the modulation transfer function (MTF) cutoff, objective scattering index (OSI), Strehl ratio (SR) and the predicted visual acuities (PVAs). Visual function was assessed by visual acuity, monocular contrast sensitivity function (CSF) across five spatial frequencies and the area under the log contrast sensitivity function (AULCSF) that was also computed as an index for overall CSF.ResultsThe MTF cutoff and SR values both increased after 1 month of wearing the OK lenses (baseline vs. 1 month: PMTF = 0.008 and PSR = 0.049); this improvement plateaued after 3 months of lens wear (1 month vs. 3 months: PMTF = 0.626, PSR = 0.428). The corneal morphology also showed the similar change trend. The OSI showed the opposite change trend (baseline vs. 1 month: POSI 0.05).ConclusionAfter 3 months of wearing OK lenses, the subjects exhibited a decrease in optical quality, similar to corneal morphology, whereas their visual function remained largely unchanged. Thus, the optical quality was more susceptible to OK lenses than visual function in children. The initial month of OK treatment of children is a key period to be paid close attention to deterioration of optical quality and visual function.

ImportanceOptical coherence tomography angiography (OCTA) has been widely applied into children, however, few studies have assessed the repeatability and reproducibility of papillary and peripapillary VD in healthy children.ObjectiveTo assess the precision of papillary and peripapillary vascular density (VD) measurements using optical coherence tomography angiography (OCTA) and analyze the effects of the signal strength index (SSI) and axial length (AL) on precision estimates.Design, setting, and participantsThis was a prospective observational study. Seventy-eight children aged 6–16 years underwent 4.5 × 4.5 mm OCTA (RTVue XR Avanti) disc scans: two scans by one examiner (repeatability) and two additional scans by another examiner (reproducibility). Within-subject standard deviation (Sw), test-retest reproducibility (TRT), within-subject coefficient of variation (CoV), intraclass correlation coefficient (ICC), and Bland–Altman analysis were performed.Main outcomes and measuresIn repeatability measurement, the fluctuation ranges (minimum to maximum) of VD between intraexaminer A/B in Sw, TRT, CoV, and ICC were (1.05–2.17)% / (1.16–2.32)%, (2.9–6)% / (3.21–6.44)%, (1.9–4.47)% / (2.08–5)%, and (0.588–0.783)% / (0.633–0.803)%, respectively. In reproducibility measurement, the fluctuation ranges of VD in Sw, TRT, CoV, and ICC were 1.11–2.13%, 3.07–5.91%, 1.99–4.41%, and 0.644–0.777%, respectively. VD was negatively correlated with SSI in most sectors of the peripapillary (e.g., inferior nasal, temporal inferior, temporal superior, superior temporal, and superior nasal). AL was positively correlated with inferior temporal VD and negatively correlated with superior nasal VD.Conclusion and relevanceOptical coherence tomography angiography showed moderate-to-good repeatability and reproducibility for papillary and peripapillary perfusion measurements in healthy children. The SSI value affects most of the peripapillary VD, while AL affects only the temporal inferior and nasal superior peripapillary VD.

Epidemiological and clinical characteristics of patients with COVID-19 have been reported in the last two years. A few studies reported clinical course of illness of median 22 days, including viral shedding of median 20 days, but there are several cases with a longer time of viral shedding. In this study, we included four cases with a longer illness course of more than 40 days who had been discharged or still in hospital by March 15, 2020. Demographic, clinical treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records. We described the epidemiological and clinical characteristics and the course of viral shedding. Two patients had comorbidity, one with hypertension and the other with diabetes. We found smoking was not an independent risk factor. D-dimer maybe related to the severity of illness but not to the course of the illness. Nucleic acid detection suggested that maybe more sampling sites represented more virus replication sites and longer course of illness. In this study we found some non-critical severe relatively young patients whose character was different from former studies described to provide a basis for reference to assess the risk of transmission and the isolation duration of patients.

Highlights 1. PRP enhances cell viability and osteogenic differentiation of hPDLSCs. 2. Activated PRP dose-dependently increases cell autophagy. 3. Inhibition of autophagy abrogates PRP-induced osteogenic differentiation of hPDLSCs.

Objective To evaluate the immunogenicity, safety and lot-to-lot consistency of an inactivated enterovirus 71 (EV71) vaccine cultured in bioreactors with different specifications after full immunization. Methods A randomized, double-blind trial was performed in 3,000 children aged 6 ~ 35 months with six vaccine batches, which were prepared in 40 L and 150 L bioreactors for three consecutive batches respectively. Children were immunized on day 0 and 28, serum samples were collected on day 0 and 56, and neutralizing antibody titers were determined by the microcytopathic method. Immediate reactions were recorded within 30 min, local and systemic symptoms were recorded within 0 ~ 28 days, and serious adverse events were recorded within 6 months. Results After immunization with two doses of the inactivated EV71 vaccine, the neutralizing antibody GMT was 825.52 ± 4.09, and the positive conversion rate was 96.18%, with no significant difference. The 95% CI of the serum neutralizing antibody GMT ratio between the two groups after immunization with the three vaccine batches produced in the 150 L and 40 L bioreactors ranged from .67 ~ 1.5. The overall incidence of adverse reactions, mainly grade 1 reactions, for all 6 batches from 0 to 28 days after vaccination was 49.62%, with no significant difference (p = .8736). The incidence of systemic adverse reactions, primarily fever and diarrhea, was 45.14%; the incidence of local adverse reactions, primarily erythema and tenderness, was 9.43%. Conclusion The EV71 vaccine was highly immunogenic and safe in children aged 6–35 months, and 6 consecutive batches produced by the two bioreactors with different specifications were consistent.

Summary: Background: The enterovirus 71 (EV71) vaccine produced by Wuhan Institute of Biological Products Co., Ltd. (WIBP) (B-EV71) has been given to children aged 6-35 months, and it has shown good safety, immunogenicity and efficacy. However, the administration of EV71 vaccine in children aged 36-71 months, which is another target population, needs further exploration. Methods: We conducted a double-blind, randomised, controlled, non-inferiority phase III clinical trial in children aged 36-71 months, with a further comparison group of children aged 6-35 months in China. Children aged 6-71 months with no history of hand, foot and mouth disease or prior-vaccination of EV71 vaccine were eligible and recruited. Eligible participants aged 36-71 months were randomly assigned (1:1) to receive two doses of the B-EV71 vaccine (Older-B group) or the control EV71 vaccine (C-EV71 vaccine, produced by Institute of Medical Biology, Chinese Academy of Medical Sciences) (Older-C group), administered at a 30-day interval. Eligible participants aged 6-35 months were enrolled consecutively to receive two doses of the B-EV71 vaccine (Younger-B group) at a 30-day interval. Participants, investigators and those assessing outcomes were masked to the vaccine received. Non-inferiority analyses were conducted to compare the immunogenicity of EV71 vaccine in the Older-B group with that in the Older-C and Younger-B groups. Non-inferiority margins were 10% for seroconversion rate differences and 0.5 for geometric mean titre (GMT) ratios. The primary endpoints were the GMT level and seroconversion rate of anti-EV71 neutralising antibody 30 days after the second dose of vaccination. The primary analysis was performed in the per-protocol population. Safety analyses were conducted amongst participants receiving at least one dose of vaccine. This trial was registered at Chinadrugtrials.org.cn (#CTR20192345). Findings: Between June 3 and June 30, 2020, 1600 participants were enrolled and assigned, including 625 participants in the Older-B group, 625 participants in the Older-C group and 350 participants in the Younger-B group. The seroconversion rate of anti-EV71 neutralising antibody in the Older-B group (99.66%; 95% CI: 99.18%–100.00%) was non-inferior to that of the Older-C (99.32%; 95% CI: 98.65%–99.98%) and Younger-B groups (100.00%; 95% CI: 100.00%–100.00%). The differences in seroconversion rates in the Older-B group to those in the Older-C and Younger-B groups were 0.34% (95%CI: -2.17%–2.86%) and -0.34% (95%CI: -2.78%–2.09%). The GMT of the anti-EV71 neutralising antibody in the Older-B group (693.87) was also non-inferior to that in the Older-C (289.37) and Younger-B groups (634.80). The ratios of GMTs in the Older-B group to those in the Older-C and Younger-B groups were 2.67 (95%CI: 2.00–3.00) and 1.00 (95%CI: 0.75–1.00), respectively. The incidence of any adverse event (AE) related to vaccination was similar amongst the three groups (34/625 [5.44%] in the Older-B group, 32/623 [5.14%] in the Older-C group, and 26/349 [7.45%] in the Younger-B group), with only 2 (0.57%) participants having grade 3 AEs in the Younger-B group. Fifteen (0.94%) participants from these three groups had reported serious AEs (SAEs), all of which were unrelated to vaccines. Interpretation: EV71 vaccine produced by WIBP could extend to be administered to children aged 36-71 months against EV71 infection. However, the persistence of vaccine-induced immunities needs to be further investigated. Funding: Hubei Province's young medical talent program (20191229), Hubei Province's young talent program (2021), Hubei Province's young public health talent program (2021); and the Wuhan Institute of Biological Products Co., Ltd.

Cyanobacterial crusts, sensitive to changes in the moisture content, are widely distributed in the Ulan Buh Desert. Changes in precipitation patterns due to global climate change are expected to influence the carbon emission and photosynthetic carbon fixation of soil in areas covered with cyanobacterial crusts. We assessed how changes in precipitation amount and frequency affect carbon processes of Cyanobacterial Crusts. Taking average precipitation amount and frequency in August during the past 30 years as control, we established nine precipitation patterns (three amounts × three frequencies). The net carbon flux (NCF) and dark respiration rate (DRR) of cyanobacterial crusts and underlying soil were investigated. Precipitation could stimulate NCF and DRR immediately. With increasing water application times, the peak values of NCF, DRR and 12 h cumulative carbon emissions gradually decreased. Both precipitation amount and frequency significantly affected cumulative carbon emissions but without an interactive effect. Under the same frequency, cumulative carbon emissions increased with increasing precipitation amounts. Under the same total precipitation amount, cumulative carbon emissions caused by high-frequency events were the highest, followed by those of low-frequency precipitation and the control. However, such changes, against the background of a changing global climate, will result in increased carbon emissions of cyanobacterial crusts and underlying Soil, suggesting that cyanobacteria should be considered in projections of the future carbon budget.

This study aimed to explore the influence of material design parameters on the physical and mechanical properties of recycled asphalt. A Box–Behnken design was employed to determine the optimal preparation scheme for 17 groups of recycled asphalt. The effects of styreneic methyl copolymer (SMC) regenerant content, styrene–butadiene–styrene (SBS)-modified asphalt content, and shear temperature on the mechanical properties of recycled asphalt were analyzed using conventional and high/low-temperature rheological tests. The optimal processing parameters were determined by a response surface model based on multiple response indexes. The results revealed that the SBS-modified asphalt content had the most significant effect on the penetration of recycled asphalt. An increase in SMC regenerant content led to a gradual decrease in the rutting factor, while SBS-modified asphalt content had the opposite effect. The usage of SMC regenerant helped to reduce non-recoverable creep compliance by adjusting the proportion of viscoelastic–plastic components in recycled asphalt. Furthermore, the stiffness modulus results indicated that the addition of SMC regenerant improved the recovery performance of recycled asphalt at a low temperature. The recommended contents of SMC regenerant and SBS-modified asphalt are 7.88% and 150%, respectively, with a shear temperature of 157.7 °C.

PurposeTo evaluate the long-term effect of two different degrees of blue-light blocking (BB) spectacle lenses on adults’ contrast perception under various lighting conditions.MethodsIn total, 144 healthy adults aged 24.70 (±4.32 years) were recruited to this randomized controlled trial. The participants were randomly divided into three groups and used three different spectacle lenses (15% BB: 15% blue-blocking spectacle lenses; 30% BB: 30% blue-blocking spectacle lenses; RC: regular clear lenses serving as control). Contrast sensitivity under four light conditions (scotopic and photopic, both with/without glare) was measured using standard clinical tests at baseline, 1 month, 3 months and 6 months of use. The area under the log contrast sensitivity function (AULCSF) was also computed as an index for their overall contrast sensitivity across spatial frequencies.ResultsThere was no significant difference in AULCSFs among the three types of spectacle lenses under any light condition (all P > 0.81). No statistical difference was found in the AULSCF among the four time points (all P > 0.39), with no interaction between the effects of group and time (all P > 0.42).ConclusionWearing blue-light blocking lens had no clinically significant effect on adults’ long-term contrast perception under scotopic or photopic conditions, or with glare.

Stable carbon isotopes (δ13C) are a useful technique to partition the net ecosystem–atmosphere exchange (NEE) of carbon dioxide (CO2) into gross primary productivity (GPP) and respiratory (R) components. The acquisition of ecosystem flux is usually performed using the eddy covariance (EC) technique, but this method is limited under complex terrain conditions and stable atmospheric conditions. Here, we try to develop the flux partitioning theory of mountain forest ecosystem by combining isotope technology and soil respiration. We used a full growing season of isotopic profile data and soil respiration data from a temperate deciduous forest on Jiufeng Mountain to demonstrate the method and quantify its uncertainties. We found that the assessable systematic uncertainty was ± 29.97% for NEE, ±24.87% for GPP, and ± 36.82% for R. The factors that most strongly affected the uncertainties of GPP and R were canopy CO2 stomatal conductance (gco2), calculated by the Köstner model, and the carbon isotope value of the total respiration in the ecosystem at night (δ13Cn-eco), calculated by the Keeling plot method. The advantage of isotopic methods is not only the relief of terrain restrictions but also the stable atmospheric conditions. The method provides an innovative vision for the partitioning of flux in forest ecosystems, especially for mountain forests.

This study aimed to analyze the impact of different additions (0–1.25%) of yam bean powder (YBP) on myofibrillar protein (MP) gel characteristics such as the structure, water-holding capacity (WHC), chemical interaction strength of grass carp MP, and texture. The results showed that the YBP exhibited a strong water absorption capacity and filled in the protein heat-induced polymerization gel network well, which enabled the gel network to capture and retain water effectively, resulting in MP gels containing YBP with excellent WHC and gel strength (0.75%). In addition, YBP induced the formation of hydrogen and disulfide bonds in proteins and inhibited the conversion of α-helices to β-sheets and β-turn structures, facilitating the formation of high-strength gel networks (p < 0.05). In conclusion, YBP can significantly improve the thermally induced gelling properties of grass carp MP. In particular, the addition of 0.75% YBP had the best effect in terms of filling the gel network of grass carp MP, resulting in the formation of a continuous and dense protein network, leading to the composite gel with the best WHC and texture.

BackgroundLung cancer is a leading cause of death worldwide, and its incidence shows an upward trend. A study of the long-term changes in the premature death rate in lung cancer in a developed region of China has great exploratory significance to further clarify the effectiveness of intervention measures. ObjectiveThis study examined long-term changes in premature lung cancer death rates in order to understand the changes in mortality and to design future prevention plans in Pudong New Area (PNA), Shanghai, China. MethodsCancer death data were collected from the Mortality Registration System of PNA. We analyzed the crude mortality rate (CMR), age-standardized mortality rate by Segi’s world standard population (ASMRW), and years of life lost (YLL) of patients with lung cancer from 1973 to 2019. Temporal trends in the CMR, ASMRW, and YLL rate were calculated by joinpoint regression expressed as an average annual percentage change (AAPC) with the corresponding 95% CI. ResultsAll registered permanent residents in PNA (80,543,137 person-years) from 1973 to 2019 were enrolled in this study. There were 42,229 deaths from lung cancer. The CMR and ASMRW were 52.43/105 and 27.79/105 person-years, respectively. The YLL due to premature death from lung cancer was 481779.14 years, and the YLL rate was 598.16/105 person-years. The CMR and YLL rate showed significantly increasing trends in men, women, and the total population (P

PurposeThis study aimed to compare the efficacy and safety of corneal refractive therapy (CRT) lenses and vision shaping treatment (VST) lenses for myopia control in children.MethodsMedical records of 1,001 children (2,002 eyes) who had been fitted with orthokeratology lenses for over 1.5 years were retrospectively reviewed. We collected the clinical data of four types of orthokeratology (OK) lenses available: one CRT lens (brand: CRT) and three VST lenses (brands: Euclid, Alpha, and Hiline) over 1.5 years. Results were compared and analyzed using a one-way ANOVA and Pearson's chi-square test.ResultsAxial length elongation in the CRT lens group was 0.13 ± 0.02 mm faster than that in the Euclid lens, 0.1 ± 0.02 mm faster in the Alpha lens, and 0.08 ± 0.02 mm faster in the Hiline lens over the 1.5-year period (all P < 0.05). Among the subjects, 37.3% of them using the CRT lens experienced more than 1 D of refractive growth, compared with 20.2–30.8% of subjects wearing the three groups of VST lenses (all P < 0.05). A lower incidence of total adverse events was found with the CRT lenses compared with the VST lenses (P < 0.05), especially corneal staining. No difference was found in axial length elongation, refraction growth, and incidence of adverse events among the three types of VST lenses (all P > 0.05).ConclusionsCompared with the VST lenses, CRT lenses demonstrated a weaker effect on myopia control but with a better safety profile. Different types of VST lenses had similar efficacy and safety in the context of controlling myopia progression.

Epithelial mesenchymal transition (EMT) is a contributing factor in remodeling events of chronic obstructive pulmonary disease (COPD). Hydrogen sulfide (H2S) has been implicated in the pathogenesis of COPD, but the effect of H2S in regulating EMT and the underlying mechanisms is not clear. In this study, we assessed endoplasmic reticulum (ER) stress markers, EMT markers and associated signal molecules in rat lungs, bronchial epithelial cells, and human peripheral lung tissues to investigate the effect of H2S in regulating EMT and the underlying mechanisms. We found that EMT and ER stress occurred in lung epithelial cells, especially in the bronchial epithelial cells of smokers and COPD patients. In cigarette smoke (CS)-exposed rats, intraperitoneal injection of NaHS significantly alleviated CS-induced lung tissue damage, small airway fibrosis, ER stress, and EMT, while intraperitoneal injection of propargylglycine (cystathionine-gamma-lyase inhibitor) aggravated these effects induced by CS. In the nicotine-exposed 16HBE cells, an appropriate concentration of H2S donor not only inhibited nicotine-induced ER stress, but also inhibited nicotine-induced enhancement of cell migration ability and EMT. ER stress nonspecific inhibitors taurine and 4-phenyl butyric acid also inhibited nicotine-induced enhancement of cell migration ability and EMT. Both H2S and inositol-requiring enzyme 1 (IRE1) activation inhibitor 4μ8C inhibited nicotine-induced activation of IRE1, Smad2/3 and EMT. These results suggest that H2S inhibits CS- or nicotine-induced ER stress and EMT in bronchial epithelial cells and alleviates CS-induced lung tissue damage and small airway fibrosis. The IRE1 signal pathway and Smad2/3 may be responsible for the inhibitory effect of H2S.

Abstract Background Since December 2019, the outbreak of COVID-19 caused a large number of hospital admissions in China. Many patients with COVID-19 have symptoms of acute respiratory distress syndrome, even are in danger of death. This is the first study to evaluate dynamic changes of D-Dimer and Neutrophil-Lymphocyte Count Ratio (NLR) as a prognostic utility in patients with COVID-19 for clinical use. Methods In a retrospective study, we collected data from 349 hospitalized patients who diagnosed as the infection of the COVID-19 in Wuhan Pulmonary Hospital. We used ROC curves and Cox regression analysis to explore critical value (optimal cut-off point associated with Youden index) and prognostic role of dynamic changes of D-Dimer and NLR. Results Three hundred forty-nine participants were enrolled in this study and the mortality rate of the patients with laboratory diagnosed COVID-19 was 14.9%. The initial and peak value of D-Dimer and NLR in deceased patients were higher statistically compared with survivors (P

The pregnane X receptor (PXR) is a nuclear receptor that can be activated by numerous drugs and xenobiotic chemicals. PXR thereby functions as a xenobiotic sensor to coordinately regulate host responses to xenobiotics by transcriptionally regulating many genes involved in xenobiotic metabolism. We have previously reported that PXR has pro-atherogenic effects in animal models, but how PXR contributes to atherosclerosis development in different tissues or cell types remains elusive. In this study, we generated an LDL receptor-deficient mouse model with myeloid-specific PXR deficiency (PXRΔMyeLDLR−/−) to elucidate the role of macrophage PXR signaling in atherogenesis. The myeloid PXR deficiency did not affect metabolic phenotypes and plasma lipid profiles, but PXRΔMyeLDLR−/− mice had significantly decreased atherosclerosis at both aortic root and brachiocephalic arteries compared with control littermates. Interestingly, the PXR deletion did not affect macrophage adhesion and migration properties, but reduced lipid accumulation and foam cell formation in the macrophages. PXR deficiency also led to decreased expression of the scavenger receptor CD36 and impaired lipid uptake in macrophages of the PXRΔMyeLDLR−/− mice. Further, RNA-Seq analysis indicated that treatment with a prototypical PXR ligand affects the expression of many atherosclerosis-related genes in macrophages in vitro. These findings reveal a pivotal role of myeloid PXR signaling in atherosclerosis development and suggest that PXR may be a potential therapeutic target in atherosclerosis management.

Cardiac inflammation and fibrosis contribute significantly to hypertension-related adverse cardiac remodeling. IκB kinase β (IKK-β), a central coordinator of inflammation through activation of NF-κB, has been demonstrated as a key molecular link between inflammation and cardiovascular disease. However, the cell-specific contribution of IKK-β signaling toward adverse cardiac remodeling remains elusive. Cardiac fibroblasts are one of the most populous nonmyocyte cell types in the heart that play a key role in mediating cardiac fibrosis and remodeling. To investigate the function of fibroblast IKK-β, we generated inducible fibroblast-specific IKK-β–deficient mice. Here, we report an important role of IKK-β in the regulation of fibroblast functions and cardiac remodeling. Fibroblast-specific IKK-β–deficient male mice were protected from angiotensin II–induced cardiac hypertrophy, fibrosis, and macrophage infiltration. Ablation of fibroblast IKK-β inhibited angiotensin II–stimulated fibroblast proinflammatory and profibrogenic responses, leading to ameliorated cardiac remodeling and improved cardiac function in IKK-β–deficient mice. Findings from this study establish fibroblast IKK-β as a key factor regulating cardiac fibrosis and function in hypertension-related cardiac remodeling.

It is an objective reality that deaf-mute people have difficulty seeking medical treatment. Due to the lack of sign language interpreters, most hospitals in China currently do not have the ability to interpret sign language. Normal medical treatment is a luxury for deaf people. In this paper, we propose a sign language recognition system: Heart-Speaker. Heart-Speaker is applied to a deaf-mute consultation scenario. The system provides a low-cost solution for the difficult problem of treating deaf-mute patients. The doctor only needs to point the Heart-Speaker at the deaf patient and the system automatically captures the sign language movements and translates the sign language semantics. When a doctor issues a diagnosis or asks a patient a question, the system displays the corresponding sign language video and subtitles to meet the needs of two-way communication between doctors and patients. The system uses the MobileNet-YOLOv3 model to recognize sign language. It meets the needs of running on embedded terminals and provides favorable recognition accuracy. We performed experiments to verify the accuracy of the measurements. The experimental results show that the accuracy rate of Heart-Speaker in recognizing sign language can reach 90.77%.

Background: COVID-19 has been quickly spreading, making it a serious public health threat. It is important to identify phenotypes to predict the severity of disease and design an individualized treatment.Methods: We collected data from 213 COVID-19 patients in Wuhan Pulmonary Hospital from January 1 to March 30, 2020. Principal component analysis (PCA) and cluster analysis were used to classify patients.Results: We identified three distinct subgroups of COVID-19. Cluster 1 was the largest group (52.6%) and characterized by oldest age, lowest cellular immune function, and albumin levels. 38.5% of subjects were grouped into Cluster 2. Most of the lab results in Cluster 2 fell between those of Clusters 1 and 3. Cluster 3 was the smallest cluster (8.9%), characterized by youngest age and highest cellular immune function. The incidence of respiratory failure, acute respiratory distress syndrome (ARDS), heart failure, and usage of non-invasive mechanical ventilation in Cluster 1 was significantly higher than others (P < 0.05). Cluster 1 had the highest death rate of 30.4% (P = 0.005). Although there were significant differences in age between Clusters 2 and 3 (P < 0.001), we found that there was no difference in demand for medical resources.Conclusions: We identified three distinct clusters of the COVID-19 patients. The results show that age alone could not be used to assess a patient's condition. Specifically, management of albumin, and immune function are important in reducing the severity of disease.

AMD3100 is a small-molecule inhibitor of the C-X-C motif chemokine ligand 12/C-X-C chemokine receptor type 4 (CXCL12/CXCR4) axis, while its role in aggrecan metabolism is unclear. We hypothesized that the AMD3100 modulates the transforming growth factor-β1 (TGF-β1)-induced expression of tissue inhibitor of metalloproteinase-3 (TIMP-3) in chondrocytes. We evaluated expression of CXCL12/CXCR4 and TIMP-3 in the knee joints of rats with and without osteoarthritis (OA) by immunohistochemistry, immunofluorescence, Western blotting, and enzyme-linked immunosorbent assay (ELISA). The rats were divided into sham control, destabilization of the medial meniscus/AMD3100-treated (DMM/AMD3100-treated), and DMM/phosphate-buffered saline (PBS)-treated groups. After 6 weeks, the rats were euthanized and subjected to histological and immunohistochemical analyses. Also, interleukin (IL)-1-pretreated primary chondrocytes were cultured in the presence of empty control (−, −), CXCL12a (+,−), CXCL12a + small interfering RNA (siRNA) CXCR4 (+,+), or CXCL12a + siNC (+NC), and the expression levels of target markers were evaluated by Western blotting and real-time reverse transcription PCR (RT-PCR). The CXCL12/CXCR4 levels were higher, and the expression of TIMP-3 was lower, in the OA rats compared to the healthy control rats. The rats in the DMM/AMD3100-treated group revealed a markedly decreased immunological response and mild pathology. Treatment with CXCL12a increased expression of aggrecan and disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5) and suppressed that of TIMP-3 in IL-1-pretreated primary chondrocytes. TGF-β1 increased expression of TIMP-3, and this increase was reversed by CXCL12a via the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Moreover, these effects were inhibited by the CXCR4 antagonist AMD3100 and the PI3K inhibitor LY303511. In conclusion, inhibition of the CXCL12a/CXCR4 signaling axis maintained TIMP-3 expression via the PI3K/Akt pathway. Our findings provide insight into the mechanism by which AMD3100 prevents OA.

Climate change and human activities have profoundly affected the world with extreme precipitation, heat waves, water scarcity, frequent floods and intense droughts. It is acknowledged that climate change will persist and perhaps intensify in the future, and it is thus meaningful to explore the quantitative impacts of these changes on hydrological regimes. The Jiulong River basin serves as an important watershed on the southeast coast of China. However, future hydrological changes under the combined impacts of climate change and land use change have been barely investigated. In this study, the climate outputs from five general circulation models (GCMs) under the Coupled Model Intercomparison Project Phase 6 (CMIP6) were corrected and spatially downscaled by a statistical downscaling method combining quantile mapping and machine learning. The future high-resolution land use maps were projected by the CA–Markov model with land use changes from the Land-Use Harmonization 2 (LUH2) as constraints. The future dynamic vegetation process was projected by the Biome-GBC model, and then, the future hydrological process under four representative concentration pathways and shared socioeconomic pathways (RCP–SSP) combined scenarios was simulated by a distributed hydrological model. Based on the copula method, the flood frequency and corresponding return periods were derived. The results demonstrated that future precipitation and air temperature would continue to rise, and future land use changes would have different developing pathways determined by the designs in various SSP–RCPs. Under the combined impacts of climate and land use change, the total available water resources will increase due to increasing precipitation, and the high flow and low flow will both increase at three stations under the four SSP–RCPs. The annual 1-day maximum discharge is projected to increase by 67–133% in the last decade of the 21st century, and the annual 7-day minimum discharge is projected to increase by 19–39%. The flood frequency analysis showed that the Jiulong River basin would face more frequent floods in the future. By the end of the 21st century, the station-average frequency of a historical 100-year flood will increase by 122% under the most optimistic scenario (SSP126) and increase by 213% under the scenario of greatest regional rivalry (SSP370). We demonstrated that climate change would be the major cause for the increase in future high flows and that land use change would dominate future changes in low flows. Finally, we recommend integrated and sustainable water management systems to tackle future challenges in this coastal basin.

In coastal areas of southeastern China, multiple flood drivers such as river flow, precipitation and coastal water level can lead to compound flooding which is often much greater than flooding simulated by one flood driver in isolation. Bivariate probability distributions accounting for compound flooding from river discharge and sea level were constructed based on MvCAT (Multivariate Copula Analysis Toolbox) combined with goodness of fit tests in 15 coastal-estuarine regions of Southeastern China. Flood typing-based bivariate probability distributions considering multiple flood-generating mechanisms were also built. Our results indicated that the performance of flood typing-based bivariate distribution was not significantly better than the bivariate probability distribution in coastal-estuarine regions based on the Mann–Whitney U test; the compounding effects of river discharge and sea level had limited impact on bivariate return periods, but had greater impact on coastal flooding risk in terms of design values. Ignoring compounding effects of river discharge and sea level leads to significant underestimation of design values. The results suggest that the compounding effect of river discharge and sea level should be considered when calculating design values in coastal flood risk assessment.

Neutralizing antibodies (NTAbs) is a major criterion for evaluation the immunogenicity of many vaccines, for example, poliovirus and EV71 vaccine. Here, we firstly discovered that polyclonal antibodies induced by inactivated CVA16 vaccine and lived CVA16 virus have poor ability to neutralize circulating CVA16 strains in vitro. However, the passive transfer of poorly neutralizing polyclonal antibodies can protect suckling mice from lethally challenged with circulating strains in vivo. In addition, the obvious dose response was found between the titer of antibodies and the survival rate. Interestingly, poorly neutralizing polyclonal antibodies against circulating CVA16 strains, have good ability to neutralize prototype strain G10 in vitro. Between G10 and circulating CVA16 strains, there are total 47 variant sites in capsid, which are near the interface of VP1, VP2, and VP3, and close to 2-fold axis. Based on the structure of CVA16, the obvious structural changes were observed in residue 213 of VP1 GH loop, residue 139 of VP2 EF loop, and residues 59, 182 and 183 of VP3 GH loop. What we found may provide a new sight for the development of CVA16 vaccine.

Heat stress (HS) is a major stressor for laying hens. It causes enormous financial losses worldwide annually. The purpose of this study was to investigate the effect and mechanism of a probiotic mixture of Bacillus subtilis and Enterococcus faecium on the performance of laying hens under HS. Eight hundred and fifty-six commercial laying hens (Hy-Line Brown, aged 40 weeks) were randomly allocated to three groups, Group C (26 °C), Group H (33 °C) and Group H + PM (33 °C + probiotic mixture), respectively. The trial lasted for 20 days. Compared with Group H, we demonstrated that treatment with the probiotic mixture significantly increased the egg production rate, average daily feed intake (ADFI), and egg weight of laying hens under HS (p

Background Obesity‐associated chronic inflammation has been known to contribute to atherosclerosis development, but the underlying mechanisms remain elusive. Recent studies have revealed novel functions of IKKβ (inhibitor of NF‐κB [nuclear factor κB] kinase β), a key coordinator of inflammation through activation of NF‐κB, in atherosclerosis and adipose tissue development. However, it is not clear whether IKKβ signaling in adipocytes can also affect atherogenesis. This study aims to investigate the impact of adipocyte IKKβ expression on atherosclerosis development in lean and obese LDLR (low‐density lipoprotein receptor)–deficient (LDLR−/−) mice. Methods and Results To define the role of adipocyte IKKβ in atherogenesis, we generated adipocyte‐specific IKKβ‐deficient LDLR−/− (IKKβΔAdLDLR−/−) mice. Targeted deletion of IKKβ in adipocytes did not affect adiposity and atherosclerosis in lean LDLR−/− mice when fed a low‐fat diet. In response to high‐fat feeding, however, IKKβΔAdLDLR−/− mice had defective adipose remodeling and increased adipose tissue and systemic inflammation. Deficiency of adipocyte IKKβ did not affect atherosclerotic lesion sizes but resulted in enhanced lesional inflammation and increased plaque vulnerability in obese IKKβΔAdLDLR−/− mice. Conclusions These data demonstrate that adipocyte IKKβ signaling affects the evolution of atherosclerosis plaque vulnerability in obese LDLR−/− mice. This study suggests that the functions of IKKβ signaling in atherogenesis are complex, and IKKβ in different cell types or tissues may have different effects on atherosclerosis development.

Chicken mitochondrial DNA is a circular molecule comprising ~16.8 kb. In this study, we used next-generation sequencing to investigate mitochondrial heteroplasmy in the whole chicken mitochondrial genome. Based on heteroplasmic detection thresholds at the 0.5% level, 178 cases of heteroplasmy were identified in the chicken mitochondrial genome, where 83% were due to nucleotide transitions. D-loop regionwas hot spot region for mtDNA heteroplasmy in the chicken since 130 cases of heteroplasmy were located in these regions. Heteroplasmy varied among intraindividual tissues with allele-specific, position-specific, and tissue-specific features. Skeletal muscle had the highest abundance of heteroplasmy. Cases of heteroplasmy at mt.G8682A and mt.G16121A were validated by PCR-restriction fragment length polymorphism analysis, which showed that both had low ratios of heteroplasmy occurrence in five natural breeds. Polymorphic sites were easy to distinguish. Based on NGS data for crureus tissues, mitochondrial mutation/heteroplasmy exhibited clear maternal inheritance features at the whole mitochondrial genomic level. Further investigations of the heterogeneity of the mt.A5694T and mt.T5718G transitions between generations using pyrosequencing based on pedigree information indicated that the degree of heteroplasmy and the occurrence ratio of heteroplasmy decreased greatly from the F0 to F1 generations in the mt.A5694T and mt.T5718G site. Thus, the intergenerational transmission of heteroplasmy in chicken mtDNA exhibited a rapid shift toward homoplasmy within a single generation. Our findings indicate that heteroplasmy is a widespread phenomenon in chicken mitochondrial genome, in which most sites exhibit low heteroplasmy and the allele frequency at heteroplasmic sites changes significantly during transmission events. It suggests that heteroplasmy may be under negative selection to some degree in the chicken.

In the context of climate change, natural gas is becoming increasingly important for low-carbon development in China. The gap between the demand and supply of natural gas, domestically, and China’s high dependence on foreign sources, highlights the importance of ensuring a secure system for supplying natural gas in the country. This study applied ecological network analysis, a powerful systems-oriented method, to simulate interactions between different nodes of the natural gas supply system and to evaluate the system’s security level. Two network models were constructed at the regional and national layers, respectively, by dividing external natural gas suppliers into multiple regions and countries. These models were used to evaluate the overall security level and related characteristics of China’s natural gas supply system from 2000 to 2012. The results showed stable improvement in the system’s security during this period. With the exceptions of some specific indicators (e.g., the mutualism index (MI)), analyses of network information and structure yielded the mostly similar results for the two models. In conclusion, a regional layer (RL) network model is considered more economical than a national layer (NL) model for evaluating the overall security of China’s natural gas supply system, especially when available data are limited.