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Zhao-Hua Wang,1,* Chang Shu,2,* Xiao Ran,1 Cui-Hong Xie,1 Lei Zhang2 1Department of Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of China; 2Department of Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lei ZhangDepartment of Surgery, Tongji Hospital, 1095 Jiefang Avenue, Wuhan 430030, People’s Republic of ChinaTel +86-27-83665312Email zhangl@tjh.tjmu.edu.cnBackground: Coronavirus disease 2019 (COVID-19) is a worldwide pandemic outbreak with a high mortality. Prognostic factors of critically ill patients with COVID-19 have not been fully elucidated yet.Methods: In the present study, 59 patients with COVID-19 from the intensive care unit of the Caidian Branch of Tongji Hospital were enrolled. Epidemiological, demographic, clinical, laboratory, radiological, treatment data, and clinical outcomes were collected. Prognostic factors were statistically defined.Results: Of the 59 patients studied (67.4± 11.3 years), 38 patients were male, 51 had underlying diseases, and 41 patients died during admission. Compared with the survivors, the deceased patients were of older age, had more smoking history, severer fatigue, and diarrhea, a higher incidence of multiple organ injuries, more deteriorative lymphopenia and thrombocytopenia, remarkably impaired cellular immune response, and strengthened cytokine release. Age higher than 70 (OR=2.76, 95% CI=1.45– 5.23), arrhythmia (OR=4.76, 95% CI=1.59– 14.25), and a Sequential Organ Failure Assessment (SOFA) score above 4 (OR=5.16, 95% CI=1.29– 20.55) were identified as risk factors for mortality of patients.Conclusion: Critically ill COVID-19 patients aged higher than 70, arrhythmia, or a SOFA score above 4 have a high risk of mortality, and need prior medical intervention.Keywords: severe acute respiratory coronavirus 2, pneumonia, critically ill, mortality, prognostic factor

Si Wen,1,* Zhao-Hua Wang,2,* Cong-Xiao Zhang,1 Ying Yang,1 Qiu-Ling Fan1 1Department of Nephrology, First Hospital of China Medical University, Shenyang, People’s Republic of China; 2Affiliated Dalian Friendship Hospital of Dalian Medical University, Dalian, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qiu-Ling FanDepartment of Nephrology, First Hospital of China Medical University, No. 155 Nanjing Bei Street, Shenyang 110001, People’s Republic of ChinaTel +86 13904012680Email cmufql@163.comBackground: Apoptosis has been repeatedly linked with diabetic kidney disease (DKD), which is a programmed cell death mediated by effector caspases-3, 6 and 7, targeting > 600 substrates. However, the pathophysiologic correlations of this process remain obscure. As a putative tumor suppressor, gasdermin E (GSDME) was recently reported to be cleaved by caspase-3 to produce a GSDME-N fragment which targets the plasma membrane to switch apoptosis to secondary necrosis. However, it remains elusive whether GSDME is involved in the regulation of DKD.Methods: To evaluate the therapeutic potential of caspase-3 inhibition in DKD, we administered caspase-3 inhibitor Z-DEVD-FMK to STZ-induced diabetic mice for eight weeks. Albuminuria, renal function, pathological changes, and indicators of secondary necrosis and fibrosis were evaluated. In vitro, human tubule epithelial cells (HK-2 cells) were subjected to high-glucose treatment. Secondary necrosis was determined by LDH release, GSDME cleavage, and morphological feature under confocal microscopy. Z-DEVD-FMK and GSDME inhibition by shRNA were administered to suppress the cleavage and expression of GSDME. Flow cytometry, cytotoxicity assay and immunoblot were used to assess cell death and fibrogenesis.Results: Caspase-3 inhibition by Z-DEVD-FMK ameliorated albuminuria, renal function, and tubulointerstitial fibrosis in diabetic mice. The nephroprotection mediated by Z-DEVD-FMK was potentially associated with inhibition of GSDME. In vitro, molecular and morphological features of secondary necrosis were observed in glucose-stressed HK-2 cells, evidenced by active GSDME cleavage, ballooning of the cell membrane, and release of cellular contents. Here we showed that caspase-3 inhibition prevented GSDME activation and cell death in glucose-treated tubular cells. Specifically, knocking down GSDME directly inhibited secondary necrosis and fibrogenesis.Conclusion: These data suggest GSDME-dependent secondary necrosis plays a crucial role in renal injury, and provides a new insight into the pathogenesis of DKD and a promising target for its treatment.Keywords: GSDME, DFNA5, secondary necrosis, diabetic kidney disease, Z-DEVD-FMK

Objective: To investigate the potential molecular mechanism of Xin Hui Tong Formula (XHTF) in the treatment of coronary heart disease (CHD) by using network pharmacology and bioinformatics. Methods: The targets network of CHD was constructed through Therapeutic Targets Database (TTD) and Drugbank database; The XHTF pharmacodynamic molecule-targets network and the XHTF pharmacodynamic molecule-CHD targets network were explored by the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP). And the multi-targets mechanism and molecular regulation network of XHTF in the treatment of CHD were explored from multiple perspectives by Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) database pathway enrichment analysis. Results: A total of 88 CHD targets were screened out through the Therapeutic Targets and the Drugbank database. 393 compounds and corresponding 205 drug targets of XHTF were retrieved from TCMSP. A total of 13 known targets directly related to the development of CHD were retrieved from the disease-related databases: TP53, MAPK14, NFKB1, HSPA5, PLG, PTGS2, ADRB1, NOS2, CYP3A4, GRIA2, CYP2A6, GRIA1, PTGS1. XHTF also contained 118 drug targets that directly interact with CHD targets. GO enrichment analysis showed that the biological processes of 13 direct targets proteins were found to be mainly enriched in response to drug, cellular response to biotic stimulus, long-chain fatty acid metabolic process, fatty acid metabolic process and regulation of blood pressure. KEGG pathway enrichment analysis found that XHTF participated in the CHD pathological process mainly through retrograde endocannabinoid signaling, regulation of lipolysis in adipocytes, cAMP signaling pathway, chemical carcinogenesis and other pathways. Conclusions: XHTF plays a role in the treatment of CHD through multiple targets and multiple pathways, and provides a scientific basis for the theory of “virtual standard” in the treatment of CHD. Keywords: Xin Hui Tong Formula (XHTF), Coronary heart disease, Network pharmacology, Network analysis, Bioinformatics

Picosecond laser with high-repetition-rate and high pulse energy is widely favorite in many scientific and industrial applications. Some nonlinear crystals can be used to efficiently convert a near-infrared laser into a green laser or an ultraviolet laser which has a higher photon energy and a smaller focal area. Especially for high-quality and high-speed transparent hard material fabrication, green or ultraviolet picosecond laser has been found to possess unique advantages. In this paper, the experiments on high-efficiency second-harmonic-generation (SHG) and third-harmonic-generation (THG) by using a home-made all-solid-state picosecond laser amplifier and an LBO crystal are reported. The picosecond laser amplifier consists of a seed source, a regenerative amplifier and a two-stage single-pass amplifier. The seed source is a commercial all-solid-state picosecond oscillator with a pulse duration of 8.3 ps and a repetition rate of 68 MHz. The repetition rate is reduced from 68 MHz to 500 kHz by an electro-optic Pockels cell (PC), and the period doubling bifurcation is minimized by reducing the duration of high voltage in PC. Both the regenerative amplifier and the two-stage single-pass amplifier are pumped by three 30-W continuous-wave fiber-coupled laser diodes. After the regenerative amplifier, the seed laser is amplified to 4.86 W with a repetition rate of 500 kHz at 1064 nm. Then the laser power is increased to 23.2 W by a two-stage single-pass amplifier, and the M2 value of the amplified laser in the X direction and in the Y direction are 1.330 and 1.235, respectively. The final pulse duration is 13.4 ps, which is slightly stretched in the amplification chain compared with the seed pulse duration (8.3 ps). For high-efficiency SHG and THG from near-infrared to green and ultraviolet, we carefully study the optical characteristics of some nonlinear crystals, such as LBO, BBO, BIBO, CLBO, etc., and we find that the LBO crystal, which has a high damage threshold, small walk-off and high nonlinear coefficient, is the best choice for both SHG and THG. Then the parameters of the two crystals for SHG and THG are specially designed according to the phase matching condition, the walk-off and the laser parameter. As a result, a 4-mm-long type-I phase matching LBO with cutting angle of θ = 90° and φ = 11.6° is used for SHG, and a 3-mm-long type-II phase matching LBO with cutting angle of θ = 42.2° and φ = 90° is used for THG. Finally, we realize high-efficiency frequency conversion with SHG power of 12.7 W at 532 nm and THG power of 9.25 W at 355 nm. The corresponding optical-optical conversion efficiencies reach 54.7% and 39.6%, respectively.

Based on the principle of quantum coherence and quantum spatial positioning,the experimental scheme of the quantum spatial positioning is designed.The spectrum characteristics of the entanglement photons with spontaneous type-II parametric down-conversion pumped by a broadband frequency pulse laser are discussed.The characteristics of the second-order coherent function and the impact of the phase matching conditions on the quantum spatial positioning are analyzed.It is shown that awith the increase of the pump band-width,the coherence of entangled biphoton is diminished,and the measuring accuracy of the quantum spatial positioning is also reduced.

This paper demonstrates the triggering and guiding of the stationary high voltage (HV) discharges at 5–40 kV by using plasma filaments generated by femtosecond laser pulses in air. A significant reduction of the breakdown voltage threshold due to the pre-ionization of the air gap by laser filamentation is observed. The discharge experiments are performed by using laser pulses with different energy from 15–60 mJ. The electron density of filaments is detected by sonography method. The influence of the electron density of laser filaments on the triggering and guiding HV discharge is experimentally investigated. The results have shown that the behaviour of plasma filaments can strongly affect the efficiency of triggering and guiding HV discharge.

A novel reflected terahertz-emission microscopy is proposed and developed for improving the spatial resolution of THz imaging. When attaching a bow-tie antenna directly onto a thin generation crystal, the reflected THz waves can be collected and detected by a photoconductive antenna, and the spatial resolution is decided by the diameter of focused pump beam. In this way, the detected resolution can be largely improved and tunable. The configuration and characteristics of this microscopy are described in detail.

The characteristics of hot electrons produced by p-polarized femtosecond laser-solid interactions are studied. The experimental results show that the outgoing electrons are mainly emitted in three directions: along the target surface, the normal direction and the laser backward direction. The electrons flowing along the target surface are due to the confinement of the electrostatic field and the surface magnetic field, while the electrons in the normal direction due to the resonant absorption.

We investigate the effects of confined laser ablation on laser plasma propulsion. Compared with planar ablation, the cavity ablation provides an effective way to obtain a large target momentum and a high coupling coefficient. When laser pulses are focused into a cavity with 1 mm diameter and 2 mm depth, a high coupling coefficient is obtained. By using a glass layer to cover the cavity, the coupling coefficient is enhanced by 10 times. Meanwhile, it is found that with the increase of the target surface size, the target momentum presents a linear increase.