Experimental demonstration of the mechanism of steady-state microbunching.

The use of particle accelerators as photon sources has enabled advances in science and technology1. Currently the workhorses of such sources are storage-ring-based synchrotron radiation facilities2-4 and linear-accelerator-based free-electron lasers5-14. Synchrotron radiation facilities deliver photons with high repetition rates but relatively low power, owing to their temporally incoherent nature. Free-electron lasers produce radiation with high peak brightness, but their repetition rate is limited by the driving sources. The steady-state microbunching15-22 (SSMB) mechanism has been proposed to generate high-repetition, high-power radiation at wavelengths ranging from the terahertz scale to the extreme ultraviolet. This is accomplished by using microbunching-enabled multiparticle coherent enhancement of the radiation in an electron storage ring on a steady-state turn-by-turn basis. A crucial step in unveiling the potential of SSMB as a future photon source is the demonstration of its mechanism in a real machine. Here we report an experimental demonstration of the SSMB mechanism. We show that electron bunches stored in a quasi-isochronous ring can yield sub-micrometre microbunching and coherent radiation, one complete revolution after energy modulation induced by a 1,064-nanometre-wavelength laser. Our results verify that the optical phases of electrons can be correlated turn by turn at a precision of sub-laser wavelengths. On the basis of this phase correlation, we expect that SSMB will be realized by applying a phase-locked laser that interacts with the electrons turn by turn. This demonstration represents a milestone towards the implementation of an SSMB-based high-repetition, high-power photon source.

Safety, Tolerability, Pharmacokinetics, and Immunogenicity of a Monoclonal Antibody (SCTA01) Targeting SARS-CoV-2 in Healthy Adults: a Randomized, Double-Blind, Placebo-Controlled, Phase I Study.

SCTA01 is a novel monoclonal antibody with promising prophylactic and therapeutic potential for COVID-19. This study aimed to evaluate the safety, tolerability, pharmacokinetics (PK) and immunogenicity of SCTA01 in healthy adults. This was a randomized, double-blind, placebo-controlled, dose escalation phase I clinical trial. Healthy adults were randomly assigned to cohort 1 (n = 5; 3:2), cohort 2 (n = 8; 6:2), cohort 3, or cohort 4 (both n = 10; 8:2) to receive SCTA01 (5, 15, 30, and 50 mg/kg, respectively) versus placebo. All participants were followed up for clinical, laboratory, PK, and immunogenicity assessments for 84 days. The primary outcomes were the dose-limiting toxicity (DLT) and maximal tolerable dose (MTD), and the secondary outcomes included PK parameters, immunogenicity, and adverse events (AE). Of the 33 participants, 18 experienced treatment-related AEs; the frequency was 52.0% (13/25) in participants receiving SCTA01 and 62.5% (5/8) in those receiving placebo. All AEs were mild. There was no serious AE or death. No DLT was reported, and the MTD of SCTA01 was not reached. SCTA01 with a dose range of 5 to 50 mg/kg had nearly linear dose-proportional increases in Cmax and AUC parameters. An antidrug antibody response was detected in four (16.0%) participants receiving SCTA01, with low titers, between the baseline and day 28, but all became negative later. In conclusion, SCTA01 up to 50 mg/kg was safe and well-tolerated in healthy participants. Its PK parameters were nearly linear dose-proportional. (This study has been registered at ClinicalTrials.gov under identifier NCT04483375.).

Efficient generation of a high-field terahertz pulse train in bulk lithium niobate crystals by optical rectification.

We demonstrate a highly efficient method for the generation of a high-field terahertz (THz) pulse train via optical rectification (OR) in congruent lithium niobate (LN) crystals driven by temporally shaped laser pulses. A narrowband THz pulse has been successfully achieved with sub-percent level conversion efficiency and multi MV/cm peak field at 0.26 THz. For the single-cycle THz generation, we achieved a THz pulse with 373-µJ energy in a LN crystal excited by a 100-mJ laser pulse at room temperature. The conversion efficiency is further improved to 0.77 % pumped by a 20-mJ laser pulse with a smaller pump beam size (6 mm in horizontal and 15 mm in vertical). This method holds great potential for generating mJ-level narrow-band THz pulse trains, which may have a major impact in mJ-scale applications like terahertz-based accelerators and light sources.

Regulation of social behaviors by p-Stat3 via oxytocin and its receptor in the nucleus accumbens of male Brandt's voles (Lasiopodomys brandtii).

Social behavior plays a significant role in the formation of social structure and population regulation in both animals and humans. Oxytocin (OXT) and its receptor (OXTR) are well known for regulating social behaviors, but their upstream regulating factors are rarely investigated. We hypothesized that the phosphorylation of the signal transducer and activator of transcription 3 (p-Stat3) may regulate social and aggressive behaviors via the OXT system in the nucleus accumbens (NAc). To test this hypothesis, OXT, p-Stat3 inhibitor, OXTR antagonist, and OXT plus p-Stat3 inhibitor were infused, respectively, into the NAc in the brain of male Brandt's voles (Lasiopodomys brandtii) - a social rodent species in grassland of Inner Mongolia, China. Our data showed that blockage of p-Stat3-Tyr705 signaling pathway in the NAc not only increased aggressive behavior but also impaired social recognition of male Brandt's voles via its effects on the expression of local OXT and OXTR. These results have illustrated a novel signaling pathway of p-Stat3-Tyr705 in regulating social behaviors via the OXT system.

Prior-damage dynamics in a high-finesse optical enhancement cavity.

An observation of prior-damage behavior inside a high-finesse optical resonator is reported. Intra-cavity average power drops appeared with magnitude and time scale depending on the power level. Increasing further the incident laser beam power led to irreversible damage of the cavity coupling mirror surface. The origin of this phenomenon is investigated with post mortem mirror surface imaging and analysis of the signals reflected and transmitted by the enhancement cavity. Scattering losses induced by surface deformation due to a hot-spot surface contaminant is found to be most likely the dominant physics process behind this phenomenon.

The PHOSPHATE1 genes participate in salt and Pi signaling pathways and play adaptive roles during soybean evolution.

BACKGROUND: The PHOSPHATE1 (PHO1) gene family plays diverse roles in inorganic phosphate (Pi) transfer and signal transduction, and plant development. However, the functions and diversification of soybean PHO1 family are poorly understood. RESULTS: Cultivated soybean (Glycine max) was domesticated from wild soybean (Glycine soja). To illuminate their roles in this evolutionary process, we comparatively investigated the G. max PHO1 genes (GmPHO1) in Suinong 14 (SN14) and G. soja PHO1 genes (GsPHO1) in ZYD00006 (ZYD6). The sequences of the orthologous Gm-GsPHO1 pairs were grouped into two Classes. The expression of Class I in both SN14 and ZYD6 was widely but relatively high in developing fruits, whereas Class II was predominantly expressed in the roots. The whole family displayed diverse response patterns to salt stresses and Pi-starvation in roots. Between SN14 and ZYD6, most PHO1 genes responded similarly to salinity stresses, and half had sharp contrasts in response to Pi-starvation, which corroborated the differential response capacities to salinity and low-Pi stress between SN14 and ZYD6. Furthermore, in transgenic Arabidopsis plants, most Class II members and GmPHO1;H9 from Class I could enhance salt tolerance, while only two Class II genes (GmPHO1;H4 and GmPHO1;H8) differently altered sensitivity to Pi-starvation. The expression of critical genes was accordingly altered in either salt or Pi signaling pathways in transgenic Arabidopsis plants. CONCLUSIONS: Our work identifies some PHO1 genes as promising genetic materials for soybean improvement, and suggests that expression variation is decisive to functional divergence of the orthologous Gm-GsPHO1 pairs, which plays an adaptive role during soybean evolution.

Linearly polarized laser beam with generalized boundary condition and non-paraxial corrections.

Linearly polarized Gaussian beams, under the slowly varying envelope approximation, tightly focused by a perfect parabola modeled with the integral formalism of Ignatovsky are found to be well approximated with a generalized Lax series expansion beyond the paraxial approximation. This allows obtaining simple analytic formulas of the electromagnetic field in both the direct and momentum spaces. It significantly reduces computing time, especially when dealing with the problem of simulating direct laser acceleration. The series expansion formulation depends on integration constants that are linked to boundary conditions. They are found to depend significantly on the region of space over which the integral formulation is fit. Consequently, the net acceleration of electrons initially at rest is extremely sensitive to the chosen set of initial parameters due to the extreme focusing investigated here. This suggests avoiding too tight focusing schemes in order to obtain reliable predictions when the process of interest is sensitive mainly to the field and not the intensity.

MMP-2 and MMP-9 contribute to the angiogenic effect produced by hypoxia/15-HETE in pulmonary endothelial cells.

Matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) are the predominant gelatinases in the developing lung. Studies have shown that the expression of MMP-2 and MMP-9 is upregulated in hypoxic fibroblasts, 15-hydroxyeicosatetraenoic acid (15-HETE) regulated fibroblasts migration via modulating MMP-2 or MMP-9, and that hypoxia/15-HETE is a predominant contributor to the development of pulmonary arterial hypertension (PAH) through increased angiogenesis. However, the roles of MMP-2 and MMP-9 in pulmonary arterial endothelial cells (PAECs) angiogenesis as well as the molecular mechanism of hypoxia-regulated MMP-2 and MMP-9 expression have not been identified. The aim of this study was to investigate the role of MMP-2 and MMP-9 in PAEC proliferation and vascular angiogenesis and to determine the effects of hypoxia-induced 15-HETE on the expression of MMP-2 and MMP-9. Western blot, immunofluorescence, and real-time PCR were used to measure the expression of MMP-2 and MMP-9 in hypoxic PAECs. Immunohistochemical staining, flow cytometry, and tube formation as well as cell proliferation, viability, scratch-wound, and Boyden chamber migration assays were used to identify the roles and relationships between MMP-2, MMP-9, and 15-HETE in hypoxic PAECs. We found that hypoxia increased MMP-2 and MMP-9 expression in pulmonary artery endothelium both in vivo and in vitro in a time-dependent pattern. Moreover, administration of the MMP-2 and MMP-9 inhibitor MMI-166 significantly reversed hypoxia-induced increases in right ventricular systemic pressure (RVSP), right ventricular function, and thickening of the tunica media. Furthermore, up-regulation of MMP-2 and MMP-9 expression was induced by 15-HETE, which regulates PAEC proliferation, migration, and cell cycle transition that eventually leads to angiogenesis. Our study demonstrated that hypoxia increases the expression of MMP-2 and MMP-9 through the 15-lipoxygenase/15-HETE pathway, and that MMP-2 and MMP-9 promote PAEC angiogenesis. These findings suggest that MMP-2 and MMP-9 may serve as new potential therapeutic targets for the treatment of PAH.

Bone morphogenetic protein-7 inhibits endothelial-mesenchymal transition in pulmonary artery endothelial cell under hypoxia.

Pulmonary artery hypertension (PAH) is characterized by structural changes in pulmonary arteries. Increased numbers of cells expressing α-smooth muscle actin (α-SMA) is a nearly universal finding in the remodeled artery. It has been confirmed endothelial-to-mesenchymal transition (EndoMT) may be a source of those α-SMA-expressing cells. In addition, the EndoMT is reversible. Here, we show that under hypoxia, the expression of bone morphogenetic protein 7 (BMP-7) was decreased both in vivo and in vitro. We also found that under normoxia, BMP-7 deficiency induced spontaneous EndoMT and cell migration. The hypoxia-induced EndoMT and cell migration were markedly attenuated after pretreatment with rh-BMP-7. Moreover, m-TOR phosphorylation was involved in EndoMT and BMP-7 suppressed hypoxia-induced m-TORC1 phosphorylation in pulmonary artery endothelial cells. Our results demonstrate that BMP-7 attenuates the hypoxia-induced EndoMT and cell migration by suppressing the m-TORC1 signaling pathway. Our study revealed a novel mechanism underlying the hypoxia-induced EndoMT in pulmonary artery endothelial cells and suggested a new therapeutic strategy targeting EndoMT for the treatment of pulmonary arterial hypertension.

Experimental feasibility of dual-energy computed tomography based on the Thomson scattering X-ray source.

Unlike large-scale and expensive synchrotron radiation facilities, the Thomson scattering X-ray source can provide quasi-monochromatic, energy-tunable and high-brightness X-ray pulses with a small footprint and moderate cost, making it an excellent candidate for dual-energy and multi-energy imaging at laboratories and hospitals. Here, the first feasibility study on dual-energy computed tomography (CT) based on this type of light source is reported, and the effective atomic number and electron-density distribution of a standard phantom consisting of polytetrafluoroethylene, water and aluminium is derived. The experiment was carried out at the Tsinghua Thomson scattering X-ray source with peak energies of 29 keV and 68 keV. Both the reconstructed effective atomic numbers and the retrieved electron densities of the three materials were compared with their theoretical values. It was found that these values were in agreement by 0.68% and 2.60% on average for effective atomic number and electron density, respectively. These results have verified the feasibility of dual-energy CT based on the Thomson scattering X-ray source and will further expand the scope of X-ray imaging using this type of light source.

Andrographolide Induces Autophagic Cell Death and Inhibits Invasion and Metastasis of Human Osteosarcoma Cells in An Autophagy-Dependent Manner.

BACKGROUND/AIMS: Osteosarcoma (OS) is the most common primary malignant tumor of bone tissue. Although treatment effectiveness has improved, the OS survival rate has fluctuated in recent years. Andrographolide (AG) has been reported to have antitumor activity against a variety of tumors. Our aim was to investigate the effects and potential mechanisms of AG in human osteosarcoma. METHODS: Cell viability and morphological changes were assessed by MTT and live/dead assays. Apoptosis was detected using Annexin V-FITC/PI double staining, DAPI, and caspase-3 assays. Autophagy was detected with mRFP-GFP-LC3 adenovirus transfection and western blot. Cell migration and invasion were detected by wound healing assay and Transwell® experiments. RESULTS: AG dose-dependently reduced the viability of osteosarcoma cells. No increase in apoptosis was detected in AG-treated human OS MG-63 and U-2OS cells, and the pan-caspase inhibitor z-VAD did not attenuate AG-induced cell death. However, AG induced autophagy by suppressing PI3K/Akt/mTOR and enhancing JNK signaling pathways. 3-MA and Beclin-1 siRNA could reverse the cytotoxic effects of AG. In addition, AG inhibited the invasion and metastasis of OS, and this effect could be reversed with Beclin-1 siRNA. CONCLUSION: AG inhibits viability and induces autophagic death in OS cells. AG-induced autophagy inhibits the invasion and metastasis of OS.

Tunable High-Intensity Electron Bunch Train Production Based on Nonlinear Longitudinal Space Charge Oscillation.

High-intensity trains of electron bunches with tunable picosecond spacing are produced and measured experimentally with the goal of generating terahertz (THz) radiation. By imposing an initial density modulation on a relativistic electron beam and controlling the charge density over the beam propagation, density spikes of several-hundred-ampere peak current in the temporal profile, which are several times higher than the initial amplitudes, have been observed for the first time. We also demonstrate that the periodic spacing of the bunch train can be varied continuously either by tuning launching phase of a radio-frequency gun or by tuning the compression of a downstream magnetic chicane. Narrow-band coherent THz radiation from the bunch train was also measured with µJ-level energies and tunable central frequency of the spectrum in the range of ∼0.5 to 1.6 THz. Our results pave the way towards generating mJ-level narrow-band coherent THz radiation and driving high-gradient wakefield-based acceleration.

Hazardous Traffic Event Detection Using Markov Blanket and Sequential Minimal Optimization (MB-SMO).

The ability to identify hazardous traffic events is already considered as one of the most effective solutions for reducing the occurrence of crashes. Only certain particular hazardous traffic events have been studied in previous studies, which were mainly based on dedicated video stream data and GPS data. The objective of this study is twofold: (1) the Markov blanket (MB) algorithm is employed to extract the main factors associated with hazardous traffic events; (2) a model is developed to identify hazardous traffic event using driving characteristics, vehicle trajectory, and vehicle position data. Twenty-two licensed drivers were recruited to carry out a natural driving experiment in Wuhan, China, and multi-sensor information data were collected for different types of traffic events. The results indicated that a vehicle's speed, the standard deviation of speed, the standard deviation of skin conductance, the standard deviation of brake pressure, turn signal, the acceleration of steering, the standard deviation of acceleration, and the acceleration in Z (G) have significant influences on hazardous traffic events. The sequential minimal optimization (SMO) algorithm was adopted to build the identification model, and the accuracy of prediction was higher than 86%. Moreover, compared with other detection algorithms, the MB-SMO algorithm was ranked best in terms of the prediction accuracy. The conclusions can provide reference evidence for the development of dangerous situation warning products and the design of intelligent vehicles.

Demonstration of nonlinear-energy-spread compensation in relativistic electron bunches with corrugated structures.

High quality electron beams with flat distributions in both energy and current are critical for many accelerator-based scientific facilities such as free-electron lasers and MeV ultrafast electron diffraction and microscopes. In this Letter, we report on using corrugated structures to compensate for the beam nonlinear energy chirp imprinted by the curvature of the radio-frequency field, leading to a significant reduction in beam energy spread. By using a pair of corrugated structures with orthogonal orientations, we show that the quadrupole wakefields, which, otherwise, increase beam emittance, can be effectively canceled. This work also extends the applications of corrugated structures to the low beam charge (a few pC) and low beam energy (a few MeV) regime and may have a strong impact in many accelerator-based facilities.

[Extraction and purification technologies of total flavonoids from Aconitum tanguticum].

OBJECTIVE: To optimize the extraction and purification technologies of total flavonoids from Aconitum tanguticum whole plant. METHODS: With the content of total flavonoids as index, the optimum extraction conditions for the concentration, volume of alcohol, extracting time and times were selected by orthogonal optimized; Comparing the adsorption quantity (mg/g) and resolution (%), four kinds of macroporous adsorption resins including D101, AB-8, X-5 and XAD-16 were investigated for the enrichment ability of total flavonoids from Aconitum tanguticum; Concentration and pH value of sample, sampling amount, elution solvent and loading and elution velocity for the optimum adsorption resin were determined. RESULTS: The content of total flavonoids in Aconitum tanguticum was about 4.39%; The optimum extraction technique was 70% alcohol reflux extraction for three times,each time for one hour, the ratio of material and liquid was 1:10 (w/v); The optimum purification technology was: using XAD-16 macroporous resin, the initial concentration of total flavonoids of Aconitum tanguticum was 8 mg/mL, the sampling amount was 112 mg/g dry resin, the pH value was 5, the loading velocity was 3 mL/min, the elution solvent was 70% ethanol and the elution velocity was 5 mL/min. Under the optimum conditions, the average content of total flavonoids was raised from 4.39% to 46.19%. CONCLUSION: The optimum extraction and purification technologies for total flavonoids of Aconitum tanguticum were suitable for industrial production for its simplicity and responsibility.

Taxi drivers' traffic violations detection using random forest algorithm: A case study in China.

OBJECTIVE: To effectively explore the impacts of several key factors on taxi drivers' traffic violations and provide traffic management departments with scientific decisions to reduce traffic fatalities and injuries. METHODS: 43,458 electronic enforcement data about taxi drivers' traffic violations in Nanchang City, Jiangxi Province, China, from July 1, 2020, to June 30, 2021, were utilized to explore the characteristics of traffic violations. A random forest algorithm was used to predict the severity of taxi drivers' traffic violations and 11 factors affecting traffic violations, including time, road conditions, environment, and taxi companies were analyzed using the Shapley Additionality Explanation (SHAP) framework. RESULTS: Firstly, the ensemble method Balanced Bagging Classifier (BBC) was applied to balance the dataset. The results showed that the imbalance ratio (IR) of the original imbalanced dataset reduced from 6.61% to 2.60%. Moreover, a prediction model for the severity of taxi drivers' traffic violations was established by using the Random Forest, and the results showed that accuracy, m_F1, m_G-mean, m_AUC, and m_AP obtained 0.877, 0.849, 0.599, 0.976, and 0.957, respectively. Compared with the algorithms of Decision Tree, XG Boost, Ada Boost, and Neural Network, the performance measures of the prediction model based on Random Forest were the best. Finally, the SHAP framework was used to improve the interpretability of the model and identify important factors affecting taxi drivers' traffic violations. The results showed that functional districts, location of the violation, and road grade were found to have a high impact on the probability of traffic violations; their mean SHAP values were 0.39, 0.36, and 0.26, respectively. CONCLUSIONS: Findings of this paper may help to discover the relationship between the influencing factors and the severity of traffic violations, and provide a theoretical basis for reducing the traffic violations of taxi drivers and improving the road safety management.

Safety and immunogenicity of a bivalent SARS-CoV-2 protein booster vaccine, SCTV01C, in adults previously vaccinated with mRNA vaccine: a randomized, double-blind, placebo-controlled phase 1/2 clinical trial.

BACKGROUND: Booster vaccination is an efficient way to address the waning protection of vaccines and immune escape of SARS-CoV-2 variants. We aimed to assess the safety and immunogenicity of SCTV01C, a novel bivalent protein vaccine as a booster for people who previously received two doses of mRNA vaccine. METHODS: In this randomized, phase 1/2 trial, adults fully vaccinated with mRNA vaccines 3-24 month earlier were enrolled. Participants received SCTV01C at 20 µg, 40 µg or placebo. The primary endpoints were adverse reactions within 7 days and immunogenicity on Day 28 after vaccination. This trial was registered with ClinicalTrials.gov (NCT05043311). FINDINGS: Between January 27 and April 28, 2022, 234 adults were randomly assigned to receive SCTV01C or placebo. The most common solicited adverse events (AEs) were Grade 1 injection-site pain (10.7%) and pyrexia (6.3%). There were no reports of Grade 3 or above solicited AE, serious AEs or AEs of special interests. On Day 28 post the booster, the geometric mean concentrations (GMCs) of the specific binding IgG antibodies to spike protein for placebo, 20 µg and 40 µg SCTV01C were 1649, 4153 and 5354 BAU/mL, with fold of increase from baseline of 1.0, 2.8 and 3.4-fold, respectively. GMTs of neutralizing antibodies against live Delta variant were 1280, 3542, and 4112, with fold of increase of 1.1, 3.9 and 4.1-fold, respectively; GMTs of neutralizing antibodies against live Omicron variant were 218, 640, and 1083, with fold of increase of 1.1, 4.4 and 5.1-fold, respectively. Participants with low neutralizing antibody titers at baseline (below the lower limit of quantitation) had 64.0 and 49.4-fold of increase in GMTs for Delta and Omicron, respectively. INTERPRETATION: The heterologous booster of SCTV01C was safe, and induced uniformly high cross-neutralization antibody responses against Delta and Omicron variants. FUNDING: Beijing Science and Technology Plan Project (Z221100007922012) and the National Key Research and Development Program of China (2022YFC0870600) supported this study.

Safety and immunogenicity of multivalent SARS-CoV-2 protein vaccines: a randomized phase 3 trial.

Background: COVID-19 vaccines that offer broad-spectrum protection are needed. We aimed to evaluate the safety and immunogenicity of multivalent vaccines, SCTV01E and SCTV01C, and compare them with an inactivated vaccine. Methods: In the phase 3 trial (ClinicalTrials.gov: NCT05323461), adult participants previously vaccinated with Sinopharm's inactivated SARS-CoV-2 vaccine (BBBIP-CorV) were assigned to receive one booster dose of BBBIP-CorV, 20 µg SCTV01C, or 30 µg SCTV01E. The primary endpoint was to evaluate the geometric mean titers (GMT) of neutralizing antibody (nAb) against the Delta and Omicron BA.1 variants on day 28 after injection. Additional endpoints included GMTs of nAb against Delta (B.1.617.2) and Omicron BA.1 variants on day 180, GMTs against BA.5 on day 28, as well as solicited adverse events (AEs) within seven days, unsolicited AEs within 28 days, and serious AEs, AEs of special interest within 180 days after vaccination. Findings: Between May 30, 2022 and October 28, 2022, a total of 1351 participants were randomized to BBBIP-CorV, SCTV01C, or SCTV01E in a 1:1:1 ratio, with immunogenicity assessments performed on the first 300 participants. For BBBIP-CorV, SCTV01C, and SCTV01E groups, the day 28 GMTs of neutralizing antibody against Omicron BA.1 were a 2.38-, 19.37-, and 28.06-fold increase from baseline; the GMTs against Omicron BA.5 were 2.07-, 15.89- and 21.11-fold increases; the GMTs against Delta variants were 1.97-, 12.76-, and 15.88-fold increases, respectively. The day 28 geometric mean ratio (GMR) of SCTV01C/BBIBP-CorV for Omicron BA.1 was 6.49 (95% CI: 4.75, 8.88), while the GMR of SCTV01E/BBIBP-CorV was 9.56 (95% CI: 6.85, 13.33). For the Delta variant, the day 28 GMR of SCTV01C/BBIBP-CorV was 6.26 (95% CI: 4.78, 8.19), and the day 28 GMR of SCTV01E/BBIBP-CorV was 7.26 (95% CI: 5.51, 9.56). On Day 180, the GMTs against Omicron BA.1 were 2.80-, 9.51-, and 15.56-fold increase from baseline, while those against Delta were 1.58-, 5.49-, and 6.63-fold for BBBIP-CorV, SCTV01C, and SCTV01E groups, respectively. Subgroup analyses showed that SCTV01C and SCTV01E induced uniformly high GMTs against both BA.1 and BA.5, demonstrating its superiority over BBIBP-CorV, regardless of baseline GMT levels. Safety and reactogenicity were similar among the three vaccines. Most AEs were Grade 1 or 2. There were 15 ≥Grade 3 AEs: 6 in the BBIBP-CorV group, 4 in the SCTV01C group and 5 in the SCTV01E group. No SAE was reported and one grade 1 AESI (Bell's palsy) was observed in SCTV01C group. Interpretation: A booster dose of the tetravalent vaccine SCTV01E consistently induced high neutralizing antibody responses against Omicron BA.1, BA.5, and Delta variants, demonstrating superiority over inactivated vaccine. There is evidence to suggest that SCTV01E may have GMT superiority over bivalent vaccine SCTV01C against Delta, BA.1 and BA.5 variants. Funding: This study was sponsored by Sinocelltech Ltd., and funded by the Beijing Science and Technology Planning Project [Z221100007922012] and the National Key Research and Development Program of China [2022YFC0870600].

Visualization and Analysis of Mapping Knowledge Domain of Heterogeneous Traffic Flow.

Mapping knowledge domain (MKD) is an important application in bibliometrics, which is a method of visually presenting and explaining newly developed interdisciplinary scientific fields using data mining, information analysis, scientific measurement, and graphic rendering. This study combines applied mathematics, visual analysis technology, information science, and scientometrics to systematically analyze the development status, research distribution, and future trend of the heterogeneous traffic flow by using the MKD software tools VOSviewer and CiteSpace. Based on the MKD and Bibliometrics approaches, 4709 articles have been studied, which were published by Science Citation Index Expanded (SCIE) and Social Sciences Citation Index (SSCI) from 2004 to 2021 in the field of heterogeneous traffic flows. Firstly, this paper presents the annual numbers of articles, origin countries, main research organizations, and groups as well as the source journals on heterogeneous traffic flow studies. Then, cocitation analysis is used to divide heterogeneous traffic flow into three main research directions, which include "heterogeneous traffic flow model," "traffic flow capacity analysis," and "traffic flow stability analysis." The keyword cooccurrence analysis is applied to identify five dominant clusters: "modeling and optimization methods," "traffic flow characteristics analysis," "driving behavior analysis," "simulation experiment," and "policies and barriers." Finally, burst keywords were studied according to the publication date to present more clearly the change of research focus and direction over time.

Visualization and Analysis of Global Vision Zero Studies and Policy Orientation in China.

As a policy that is widely used worldwide, Vision Zero is a long-term strategic goal for road safety in China. The aim of this paper is to examine the literature in the field of Vision Zero retrieved by the Web of Science (WOS) Core Collection database from 1997 to 2021 based on mapping knowledge domain (MKD) and bibliometric methods. In this paper, we analyzed the overall development level of Vision Zero at different stages using the statistical analysis of the distribution of literature years. Based on the analysis, four major research directions of Vision Zero are obtained through keywords co-occurrence analysis, including "Vision Zero in road safety", "vulnerable road users' risks", "effect of speed on severity", and "responsibility management for crashes". Furthermore, we explore the influence and development potential of each country and region of Vision Zero based on the number and citation frequency of the literature, and the distribution of time dimensions. Among the research topics, all countries and regions are clustered into four clusters, and the current status of Vision Zero for countries in the most influential clusters, which include Sweden, the United States, Australia, China, and Norway, have been presented. Finally, an analysis of road safety in China is carried out, which includes displaying the changes in the number of road accidents, fatalities, and serious injuries in China between 2009 and 2018, comparing the fatalities per 10,000 vehicles and the fatalities per 100,000 people between China and other countries, and describing China's strategic routes toward Vision Zero.