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.