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Due to waning immunity and protection against infection with SARS-CoV-2, a third dose of a homologous or heterologous COVID-19 vaccine has been proposed by health agencies for individuals who were previously primed with two doses of an inactivated COVID-19 vaccine.We did a randomised, open-label, controlled trial to evaluate the safety and immunogenicity of heterologous boost immunisation with an orally administered aerosolised adenovirus type-5 vector-based COVID-19 vaccine (Ad5-nCoV) in Chinese adults (≥18 years old) who had previously received two doses of an inactivated SARS-CoV-2 vaccine-Sinovac CoronaVac. Eligible participants were randomly assigned (1:1:1) to receive a heterologous booster vaccination with a low dose (1·0 × 10Between Sept 14 and 16, 2021, 420 participants were enrolled: 140 (33%) participants per group. Adverse reactions were reported by 26 (19%) participants in the low dose group and 33 (24%) in the high dose group within 14 days after the booster vaccination, significantly less than the 54 (39%) participants in the CoronaVac group (p0·0001). The low dose group had a serum NAb GMT of 744·4 (95% CI 520·1-1065·6) and the high dose group had a GMT of 714·1 (479·4-1063·7) 14 days after booster dose, significantly higher than the GMT in the CoronaVac group (78·5 [60·5-101·7]; p0·0001).We found that a heterologous booster vaccine with an orally administered aerosolised Ad5-nCoV is safe and highly immunogenic in adults who have previously received two doses of CoronaVac as the primary series vaccination.National Natural Science Foundation of China and Jiangsu Provincial Key Research and Development Program.

Based on the lumped parameter theory, a nonlinear bending torsion coupling dynamic model of planetary gear transmission system was established by considering the backlash, support clearance, time-varying meshing stiffness, meshing damping, transmission error and external periodic excitation. The model was solved by the Runge–Kutta method, the dynamic response was analyzed by a time domain diagram and phase diagram, and the nonlinear vibration characteristics were studied by the response curve of the speed vibration displacement. The vibration test of the planetary gearbox was carried out to verify the correctness of frequency domain response characteristics. The results show that the vibration response in the planetary gear system changes from a multiple periodic response to a single periodic response with the increase in input speed. Under the action of the backlash, time-varying meshing stiffness and meshing damping, the speed vibration displacement response curves of internal and external meshing pairs appear to form a nonlinear jump phenomenon and have a unilateral impact area, and the system presents nonlinear characteristics. The nonlinear vibration of the system can be effectively suppressed by decreasing the mesh stiffness or increasing the mesh resistance, while the vibration response displacement of the system increases by increasing the external exciting force, and the nonlinear characteristics of the system remain basically unchanged. The backlash is the main factor affecting the nonlinear frequency response of the system, but it can restrain the resonance of the system in a certain range. The spectrum characteristics of the vibration displacement signal of the planetary gearbox at different speeds are similar to the simulation results, which proves the validity of the simulation analysis model and the simulation results. It can provide a theoretical basis for the system vibration and noise reduction and a dynamic structural stability design optimization.

The dynamic load-sharing characteristics of aircraft face gear dual-power split transmission system (FGDPSTS) are taken as the research object. Considering the factors of time-varying meshing stiffness, comprehensive error, backlash, support clearance, spline clearance, torsional stiffness, and support stiffness, the dynamic load-sharing model was constructed based on the lumped-parameter method. The loaded tooth contact analysis (LTCA) simulation method was used to calculate the time-varying meshing stiffness. The dynamic load-sharing coefficient (DLSC) is obtained by using Runge–Kutta method. The influences of errors, backlash, support clearance, spline clearance, torsional stiffness and support stiffness on DLSC were analyzed, and the biggest factors affecting dynamic load-sharing performance were found out. The results show that the influence of the backlash of the two-stage herringbone gear pair on the DLSC is more sensitive. The influence of support clearance on the DLSC is less. The load-sharing coefficient increases with the increase of the installation error and eccentricity error, and the influence of the error of the two-stage gears on the system load-sharing performance is the most sensitive. The torsional stiffness has little effect on the load-sharing coefficient of one stage but has great effect on the two-stage load-sharing coefficient. The influence of support stiffness on the DLSC of two-stage is stronger. It provided a theoretical basis for the dynamic stability optimization design of the system.

A series of alkyl gallates was synthesized by reacting gallic acid with the corresponding alcohols. Their structures were determined on the basis of spectroscopic data, including NMR and MS. The antifungal activities of these compounds against plant pathogenic fungi in vitro and in vivo were assessed.

Metastasis and malignant proliferation are major obstacles to the treatment of oesophageal squamous cell carcinoma (ESCC), and UTP14A is associated with poor prognosis in ESCC. However, its mechanisms have not been fully elucidated. The TCGA and GEO databases were used to identify candidate target genes and possible downstream targets. Then, the effects were determined in vitro and in vivo through knockdown and overexpression techniques, and the mechanism was explored. UTP14A was significantly higher in the tumour tissue of ESCC patients than in normal tissue. Knockdown of UTP14A significantly suppressed the migration and proliferation of ESCC cells. The PERK/eIF2a signalling pathway was positively regulated by UTP14A, and its tumour-promoting effect was further activated by overexpression of UTP14A. In conclusion, UTP14A might promote the proliferation and metastasis of ESCC cells by inducing PERK/eIF2a signalling pathway expression.

The extent to which the presence of pleural adhesions affects the surgical and oncological outcomes of patients undergoing McKeown minimally invasive esophagectomy (MIE) for esophageal cancer (EC) has not previously been studied.Data of consecutive EC patients undergoing McKeown MIE by a single surgeon in the Department of Thoracic Surgery at Daping Hospital from November 2015 to December 2020 were collected. Patients were grouped according to the presence or absence of pleural adhesions when entering the chest cavity. Propensity score matching (PSM) was used to reduce selection bias from confounding factors. Kaplan-Meier was used to assess the survival differences.A total of 617 consecutive EC patients underwent McKeown MIE were enrolled. There were 116 patients with pleural adhesions (Group A) and 501 patients without pleural adhesions (Group B). Patients in Group A were more likely to be older than those of patients in Group B: (66.26 vs. 63.27, P = 0.001). In addition, Group A had more patients with chronic obstructive pulmonary disease (COPD) (24.1% vs. 16.8%, P = 0.04). After propensity score matching (102 matched patients in Group A and 185 matched patients in Group B), these findings were no longer statistically significant. Postoperative pulmonary infection occurred in 57 patients in Group A and in 15 patients in Group B (53.9% vs. 13.0%, P 0.001). In addition, the presence of pleural adhesions was significantly associated with the prolonged operation time (232 min vs. 210 min, P .001), length of stay (12 days vs. 10 days, P = 0.001), and hydrothorax requiring drainage (12.7% vs. 5.4%, P = 0.04). However, the disease-specific survival and disease-free survival rates were comparable between the two groups (P = 0.40 and 0.13, respectively).The presence of pleural adhesions predicted an increased operation time, length of stay, postoperative pneumonia, and hydrothorax requiring drainage of EC patients undergoing McKeown MIE, but did not exert unfavourable effect on long-term survival.

The influence of microstructural characteristics on Luders strain and mechanical properties was explored by means of altering thermo-mechanical circumstances in an intercritical annealing (IA) medium-Mn Fe-11Mn-0.09C-0.25Si (wt.%) steel. By IA of cold-rolled samples with severe plastic deformation, exclusively equiaxed dual phases were obtained because of active recovery and recrystallization. The equiaxed austenite ( $$\upgamma_{\text E}$$ ) with a larger size and inadequate chemical concentration was more readily transformed into martensite, and subsequent transformation-induced plasticity (TRIP) effect was triggered actively at relatively higher IA temperature, lessening localized deformation. In addition, grown-in dislocations were prone to multiply and migrate around a broad mean free path for coarser equiaxed ferrite ( $$\upalpha_{\text E}$$ ) due to weakening dynamic recovery; therefore, it was the ensuing increased mobility of dislocations instead of reserving plentiful initial dislocation density that facilitated the propagation velocity of Luders bands and the accumulation of work hardening. In contrast, the bimodal-grained microstructure with lath-like and equiaxed austenite ( $$\upgamma_{\text L} + \upgamma_{\text E}$$ ) satisfactorily contributed to a smaller yield point elongation (YPE) without compromise of comprehensive mechanical properties on the grounds that austenitic gradient stability gave rise to discontinuous but sustainable TRIP effect and incremental work hardening. Hence, Luders strain is closely related to the absence of work hardening in the region which yields locally. It follows that the decreased stability of retained austenite, favorable mobility of dislocations and the bimodal-grained structure all prominently make up for the insufficiency of work hardening, thereof resulting in a limited YPE.

1000 MPa grade cold-rolled duplex steel with 5 component systems was trial-produced in the laboratory. After hot rolling, pickling and cold rolling, the test steel was simulated continuous annealing on Gleeble-3800 thermal simulator. The microstructure and properties of 5 kinds of experimental steels after simulated annealing were analyzed. The results show that C and Mn elements are the basic alloy systems of all duplex steels. In the case of low Si element, the C element content of the 1000 MPa grade dual phase steel should be 0.15 % or higher, and the Mn element content should be higher than 1.8 %. Si element increased to the A3 point, while the amount of austenite was less in the two-phase region during annealing, and the volume fractionof martensiteafter the rapid cooling is insufficient; Nb element is a high-efficiency fine-grain strengthening element, which greatly improvedthe uniformity of the steel species. The fine-grained martensite islands have enhance the tempering stability of martensite and thereby to reduce the adverse strength effect from over-aging temperature.

Herein, a binuclear ruthenium(II) complex modified by calix[4]arene group has been prepared. The complex as potential inducer and stabilizer of c-myc G-quadruplex DNA and antitumor reagent were studied. Observations revealed that the complex could bind to c-myc Pu27 and Pu22 DNA strongly with constants of 1.18 × 107 (Pu27) and 4.13 × 106 M-1 (Pu22) via groove mode as determined from absorption and luminescence titrations, as well as CD spectra. Results of continuous variation analysis confirmed that the complex interacted with c-myc G-quadruplex DNA through a 1:1 binding stoichiometry. As verified by PCR-stop assay, the replication of c-myc DNA was effectively blocked by the complex with the complete inhibition at the complex concentration of 4.0 μM both for Pu27 and Pu22, suggesting that the complex could efficiently induce the formation of c-myc G-quadruplex DNA. The appearance of blue TMB solution in the visual experiment also proved that the sequences of Pu27 and Pu22 could fold into G-quadruplex under the induction of the complex. Nevertheless, the complex was found to exhibit weak stabilization ability on c-myc G-quadruplex DNA according to FRET assay, which increased the melting point of c-myc DNA only 3-3.5 °C. The experiments on Topoisomerase inhibition and cytotoxicity of the complex showed that it acted as an inhibitor of TopoI and exhibited moderate anticancer activity against MCF-7 and Huh-7 tumor cells.

Carbon neutrality has been received extensive attention in the field of wastewater treatment. The optimal management of wastewater treatment plants (WWTPs) has great significance and urgency since the serious energy and materials waste. In this study, a full-view management method based on artificial neural networks (ANNs) for energy and material savings in WWTPs was established. More than 5 years of historical operating data from two typical plants (size 40,000 t/d and 10,000 t/d) located in Chongqing, China, were obtained, and public data in the service area of each plant were systematically collected from open channels. These abundant historical and public data were used to train two ANNs (GRA-CNN-LSTM model and PCA-BPNN model) to predict the inlets/outlets wastewater quality and quantity. The overall average prediction accuracy of inlets/outlets wastewater indicators are greater than 92.60% and 93.76%, respectively. By combining the two models, more appropriate process operation strategies can be obtained 2 weeks in advance, with more than 11.20% and 16.91% reduction of energy and material costs, respectively. This proposed method can provide full-view decision support for the optimal management of WWTPs and is also expected to support carbon emission control and carbon neutrality in the field of wastewater treatment.

Benefited from the massive filling bio-carriers, the packed cage rotating biological contactors (RBCs) have better performance and application potentiality in wastewater treatment. Investigating the effects mechanism of bio-carrier filling rate is crucial for such reactors management. In this study, the pollutants removal performance, biofilms physical characteristics, and microbial communities of the biofilms under a series of bio-carrier filling rates were analyzed. The results shown, the pollutant removal rate and amount were quite different under different filling rates, and biofilms structure and microbial composition were the main factors affecting the pollutants removal performance. With the increasing filling rates, the biofilms were more mass increased (dry weight from 0.066 to 0.148 g/per carrier), thicker (from 340.30 to 850.84 μm) and lower dense (from 0.068 to 0.060 g/cm

The implementation of McKeown minimally invasive esophagectomy (MIE) is associated with a steep learning curve. However, there is no consensus on the number of cases required before effective and safe McKeown MIE can be achieved.Data on consecutive patients with esophageal carcinoma who underwent esophagectomy performed by a single surgeon in the Department of Thoracic Surgery at Daping Hospital in Chongqing, China from September 2009 to June 2019 were collected. The cumulative sum learning curve was plotted on the basis of the learning associated parameters. Propensity score matching was used to reduce selection bias from confounding factors. The Kaplan-Meier method was used to assess the survival differences.The learning curve was divided into the ascending period (cases 1-197), the plateau period (198-314), and the descending period (315-onward). After 197 cases, significant improvements in operative time (300 minutes vs 210minutes; P.001), retrieved lymph nodes (17 vs 20; P = .004), hospital length of stay (18 days vs 13 days; P = .001), major postoperative complications (38.6% vs 32.5%; P.001), vocal cord palsy (6.1% vs 0.9%; P = .04), and pulmonary complications (31.5% vs 17.1%; P = .005) were observed. In addition, after 314 cases, significant decreases in blood loss (200 mL vs 100 mL; P.001), anastomotic leak (24.8% vs 14.8%; P = .02), and chylothorax (4.3% vs 0%; P = .001) were observed. After propensity score matching, the overall and disease-free survival rates were significantly improved during the experienced period (P = .02 and .03, respectively).The initial learning phase of McKeown MIE consisted of 197 procedures in 51 months. Moreover, the surgeon's experience did have a direct impact on the long-term outcomes in patients with esophageal carcinoma.

Lymphovascular invasion (LVI) is reported to be a potential prognostic predictor in esophageal squamous cell carcinoma (ESCC) patients.To investigate the prognostic value of LVI in ESCC node-negative patients after minimally invasive esophagectomy (MIE).1406 consecutive ESCC patients who underwent MIE were reviewed retrospectively. After exclusion, 880 patients were enrolled, and 298 node-negative patients were used for the further analysis. The Kaplan-Meier method was used to examine the survival difference. Univariate and multivariate analyses were performed to identify prognostic predictors.LVI was observed in 29.4% of all patients. Totally, the proportion of LVI was increased with advanced T (p0.01) and N (p0.01) stage and poor tumor differentiation (p0.01). In the node-negative patients, a similar result was obtained in T stage (p = 0.0252) and tumor differentiation (p = 0.0080). In survival analysis, the disease-specific survival (DSS) (p = 0.0146) rate was significantly lower in node-negative patients with LVI than in those without. The difference was absent when calculating disease-free survival (DFS) (p = 0.0796). Additionally, the presence of LVI was associated with lower DSS (p = 0.0187) but not DFS (p = 0.0785) in univariate analysis in node-negative patients. Moreover, in multivariate Cox regression analysis, the presence of LVI was identified as an independent prognostic factor only in DSS (p = 0.0496) but not in DFS (p = 0.5670) in node-negative patients.LVI is associated with shorter DSS and an independent prognostic factor in ESCC node-negative patients after MIE.

To solve the dynamic load distribution mechanism of the power split transmission system of spiral bevel gears, according to the characteristics of the closed loop of power flow, the deformation coordination condition is deduced. Through the gear teeth geometric contact analysis technique, the time-varying meshing stiffness conditions in the model are solved. The linear time-varying dynamic model of the torsional vibration of the bevel gear split transmission system is established by the lumped mass parameter method. Considering the influence of time-varying mesh stiffness excitation conditions and damping, the dynamic differential equations are treated in a dimensionless way. The dynamic load change and dynamic response characteristics of the system are obtained by numerical solution, and the influence of parameters such as speed and damping on dynamic power flow and dynamic characteristics of the system is revealed. The results show that with an increase of meshing damping ratio, dynamic power flow of each gear pair changes little, and the vibration acceleration and its root mean square value of each gear pair of the system are smaller. With an increase in speed, vibration acceleration and its average amplitude increase.

Power split two-stage five-branching star gearing drive system has been widely used in the aviation engine reducer and the helicopter’s main reducer. For the problem of load sharing characteristics of this system, a static load-sharing calculation model is established. According to the power flow closed loop characteristics of the whole system, the torque equilibrium condition and deformation compatibility condition of the system are established. The load sharing coefficient of the star gears and the system is calculated by using the principle of the integrated equivalent mesh error and the static equilibrium condition of the floating element. Further, the influence of manufacturing error, installation error and floating on load sharing coefficient is analyzed. When the load sharing characteristic is independently influenced by the error, the load sharing coefficient of each star gear changes periodically with time. Basic component floating can significantly improve the load sharing performance. The correctness of the theoretical algorithm is verified by experiments. A new algorithm is proposed for engineering application.

A polypyridyl ruthenium(II) complex with hydroxyquinoline-derived ligand has been synthesized and characterized. The ability to act as telomeric quadruplex inducer and stabilizer, and quadruplex-binding properties of the complex have been evaluated by absorption and emission analyses, fluorescent intercalator displacement (FID) titrations, circular dichroism (CD) spectroscopy, polymerase chain reaction (PCR) stop assay, color reaction studies, fluorescence resonance energy transfer (FRET) melting assay, Job plot, and molecular modeling. Observations revealed that the complex could well induce and stabilize the formation of antiparallel G-quadruplex of telomeric DNA in the presence or absence of metal cations, and showed superior G-quadruplex selectivity over duplex DNA with remarkable ΔTm value of 18.0 °C even at 50-fold excessive supplies of calf thymus (ct) DNA. The complex exhibited high interaction affinity of 2.56 × 106 M−1 with G-quadruplex DNA and evident luminescence enhancements of 3.1 and 4.2 times for quadruplex binding in Na+ and K+ buffer, respectively. In addition, the 1:1 [quadruplex]/[complex] binding mode ratio was determined. The results suggest that the complex can be developed as potential anticancer reagent through binding and stabilization of G-quadruplex DNA.

Background Several immune checkpoint inhibitors (ICIs), represented by programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) antibodies, have been approved for treatment of various malignant tumors (including advanced esophageal cancer) worldwide, and previous studies confirmed that they can significantly improve overall survival.1 However, there has been limited research on the use of ICIs as neoadjuvant therapy for patients with esophageal cancer. Toripalimab is a humanized IgG4 monoclonal antibody that targets PD-1. The objective of this study is to evaluate the efficacy and safety of toripalimab plus chemotherapy as a neoadjuvant therapy regimen for treatment of patients with locally advanced esophageal squamous cell carcinoma (ESCC). Methods This single-arm, single-center study enrolled patients with ESCC at clinical stage T2-T4/N0-N2/M0, who were eligible for radical resection and regional lymph node dissection. The patients received 2–3 cycles of toripalimab (240 mg d1, Q3W) in combination with nab-paclitaxel (260 mg/m2 d1, Q3W) and carboplatin (AUC=5 d1, Q3W) before surgery. Preoperative evaluation was performed within 4 weeks after the last administration of chemotherapy. The primary endpoints were pathologic complete response (PCR) and major pathologic response (MPR), and the secondary endpoints were safety and feasibility of the neoadjuvant immunotherapy. Results Seventeen patients diagnosed with ESCC at a pre-treatment clinical stage of T2-T4/N0-N2/M0 were included. After neoadjuvant therapy, 15 of 17 patients (88.2%) experienced downstaging and met the surgical criteria. Twelve patients (80.0%) underwent surgery without delay and 3 patients (20.0%) refused surgery. The tumors were completely removed in all 12 patients (R0 resection rate: 100%). Seven patients (58.3%) achieved MPR and 2 (16.7%) achieved PCR. The median post-surgical follow-up time was 4.5 months, and there were no recurrences. Treatment-related adverse events (TRAEs) of the neoadjuvant therapy were tolerable. Grade 3 or higher TRAEs occurred in 2 patients (11.8%), but these did not delay surgery. Conclusions Toripalimab in combination with chemotherapy as neoadjuvant therapy showed promising anti-tumor activity with acceptable tolerance for locally advanced ESCC, as demonstrated by reducing the tumor burden, improving the R0 resection rate, reducing the postoperative recurrence rate, and no delays in surgery. Acknowledgements N/A Ethics Approval This study was approved by the Ethics Board of the Army Medical center of the PLA, approval number 142(2018). Consent Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal. Reference Wu X, Gu Z, Chen Y, et al. Application of PD-1 blockade in cancer immunotherapy. Comput Struct Biotechnol J 2019;17:661–674.

Summary There is growing focus on the relationship between surgical start time and postoperative outcomes. However, the extent to which the operation start time affects the surgical and oncological outcomes of patients undergoing esophagectomy has not previously been studied. The purpose of this retrospective study was to investigate the potential effect of surgical start time on the short- and long-term outcomes for patients who underwent thoracoscopic–laparoscopic McKeown esophagectomy. From September 2009 to June 2019, a total of 700 consecutive patients suffering from esophageal cancer underwent thoracoscopic–laparoscopic McKeown esophagectomy in the Department of Thoracic Surgery at Daping Hospital. Among these patients, 166 esophagectomies were performed on the same day and were classified as the first- or second-start group. Patients in the first-start group were more likely to be older than those in the second-start group: (64.73 vs. 61.28, P = 0.002). In addition, patients with diabetes mellitus were more likely to be first-start cases (8.4 vs. 1.2%). After propensity score matching (52 matched patients in first-start cases and 52 matched patients in second-start cases), these findings were no longer statistically significant. There was no difference in the incidence rate of peri- or postoperative adverse events between the first- and second-start groups. The disease-specific survival rates and disease-free survival rates were comparable between the two groups (P = 0.236 and 0.292, respectively). On the basis of the present results, a later start time does not negatively affect the short- or long-term outcomes of patients undergoing minimally invasive McKeown esophagectomy.

Background Angiogenesis is a critical step in the growth of pancreatic neuroendocrine tumors (PNETs) and may be a selective target for PNET therapy. However, PNETs are robustly resistant to current anti-angiogenic therapies that primarily target the VEGFR pathway. Thus, the mechanism of PNET angiogenesis urgently needs to be clarified. Methods Dataset analysis was used to identify angiogenesis-related genes in PNETs. Immunohistochemistry was performed to determine the relationship among Neuropilin 2 (NRP2), VEGFR2 and CD31. Cell proliferation, wound-healing and tube formation assays were performed to clarify the function of NRP2 in angiogenesis. The mechanism involved in NRP2-induced angiogenesis was detected by constructing plasmids with mutant variants and performing Western blot, and immunofluorescence assays. A mouse model was used to evaluate the effect of the NRP2 antibody in vivo, and clinical data were collected from patient records to verify the association between NRP2 and patient prognosis. Results NRP2, a VEGFR2 co-receptor, was positively correlated with vascularity but not with VEGFR2 in PNET tissues. NRP2 promoted the migration of human umbilical vein endothelial cells (HUVECs) cultured in the presence of conditioned medium PNET cells via a VEGF/VEGFR2-independent pathway. Moreover, NRP2 induced F-actin polymerization by activating the actin-binding protein cofilin. Cofilin phosphatase slingshot-1 (SSH1) was highly expressed in NRP2-activating cofilin, and silencing SSH1 ameliorated NRP2-activated HUVEC migration and F-actin polymerization. Furthermore, blocking NRP2 in vivo suppressed PNET angiogenesis and tumor growth. Finally, elevated NRP2 expression was associated with poor prognosis in PNET patients. Conclusion Vascular NRP2 promotes PNET angiogenesis by activating the SSH1/cofilin/actin axis. Our findings demonstrate that NRP2 is an important regulator of angiogenesis and a potential therapeutic target of anti-angiogenesis therapy for PNET.

Background The COVID-19 pandemic has spread worldwide. However, the impact of lipid profile and lipid-lowering treatment on clinical endpoints in COVID-19 have not previously been investigated. Methods In this retrospective, multicenter cohort study, we consecutively enrolled 430 adult COVID-19 patients from two Chinese hospitals (one each in Chengdu and Wuhan) admitted during February 2020 and followed-up until April 30. Demographic, metabolic profile, laboratory, treatment and clinical endpoint data including in-hospital death and recurrence of COVID-19, were collected. Results In Chengdu patients, univariable and multivariable Cox regression showed that the low-density lipoprotein cholesterol (LDL-C) dyslipidemia on admission was associated with the recurrence of COVID-19 during the follow-up period. In Wuhan cohort, the patients with triglycerides hyperlipemia had an increased risk of in-hospital death. However, in both cohorts, statin therapy during COVID-19 course did not affect these clinical endpoints. Compared to the Chengdu cohort, the Wuhan patients tended to have more severe COVID-19 but, unexpectedly, had lower levels of serum lipid. It is of interesting to notice that the relationship between the observed biomarkers of inflammation and lipid do not match the relationship between the organ function measures and this lipid. Conclusions The baseline dyslipidemia should be considered as a risk factor for poor prognosis and recurrence of COVID-19. The lipid level may be altered during COVID-19 course, since lipidology may be distinctly affected by both inflammation and organic damage for SARS-CoV-2. Further investigation is needed on the role of use of lipid-lowering therapy among patients with COVID-19 infections.

Background Angiogenesis is a critical step in pancreatic neuroendocrine tumour (PNET) growth and may be a selective target for PNET therapy. However, PNET is robustly resistant to current antiangiogenic therapies which primarily target the VEGFR pathway. Thus, PNET angiogenesis mechanism was urgently to be clarified. Methods Dataset analysis was used to identify PNET angiogenesis related genes. Immunohistochemistry was performed to determine relation among Neuropilin 2 (NRP2), VEGFR2 and CD31. Cell proliferation, wound-healing and tube formation assay were investigated to clarify the function of NRP2 in angiogenesis. The mechanism involved in NRP2 inducing angiogenesis was detected by mutant construction, Western blot, and immunofluorescence assay. In vivo, mice model was performed to evaluate the effect of NRP2 antibody, and clinical data was recruited to verify association between NRP2 and patients prognosis. Results NRP2, a VEGFR2 co-receptor, positively correlated with vascularity rather than with VEGFR2 in PNET tissues. NRP2 promoted PNET cell medium-treated HUVEC cell migration via a VEGF/VEGFR2-independent pathway. Moreover, NRP2 induced F-actin polymerization by activating the actin-binding protein cofilin. Mechanistically, cofilin phosphatase slingshot-1 (SSH1) was highly expressed involved in NRP2-activating cofilin. Silencing SSH1 rescued NRP2-activated HUVEC cell migration and F-actin polymerization. Furthermore, blocking NRP2 in vivo suppressed PNET angiogenesis and tumour growth. High NRP2 expression was associated with poor prognosis in PNET patients. Conclusion Vascular NRP2 promotes PNET angiogenesis via activating SSH1/cofilin/actin axis. Our findings demonstrate NRP2 to be an important regulator of angiogenesis and potential therapeutic target of anti-angiogenesis therapy for PNET.

Inspired by a serious fire accident on the cable-stayed bridge, the characteristics of this type of cable fire were investigated pertinently with experiment. And some important parameters, such as temperature distribution and flame height, were measured. The behaviors of fire growth and fire propagation were analyzed; furthermore, fire spread rate was obtained. Additionally, the effectiveness of fire extinguishing methods used in such cable fires was also examined. The results show that the special cables layout and material composition seriously influenced fire behaviors. When internal steel strands were ignited, the polyethylene material on its surface would melt and drop at high temperature, causing that external burning drops penetrated into the interior, which could gradually ignite the unburned part and flaring up the fire. The HDPE sheath originally as a protected component, once ignited, would generate a large amount of burning molten drops, dramatically promoting the fire development to the underneath cable. As observed in fire extinguishing experiments, dry powder, one method recommended by NFPA, showed a re-ignition phenomenon. By comparison, water, one method deprecated in standard, contrarily brought about good effects in fire extinguishing due to an effective cooling effects for inner steel.

High-temperature plane-strain compression of a Ti-6Al-2Sn-4Zr-2Mo (Ti-6242) alloy with a lamellar structure was applied by a thermal simulation machine Gleeble 3800 at a temperature of 1223-1370 K and a strain rate of 0.01-10 s−1. Constitutive relations between the flow stress and strain at different temperatures and strain rates were constructed based on the Arrhenius equation. Processing maps based on the dynamic material model at strains of 0.5, 1.0, and 1.25 were also constructed to analyze the mechanism and instability of high-temperature deformation. Dynamic recrystallization was found to occur at 1223-1313 K and 0.01-0.1 s−1, with a peak efficiency of power dissipation of 70%. Observations of the microstructure demonstrated that α platelets and dynamic globularization were responsible for dynamic softening in the α + β phase field. Flow instability behaviors occurred at 1263-1343 K/1.78-10 s−1, 1233-1283 K/0.1-3.16 s−1, and 1353-1373 K/0.56-1.78 s−1, and adiabatic shear bands and microcracks were observed in these domains. Thus, for the lamellar Ti-6242 alloy, the recommended hot rolling parameters were 1243-1333 K and 0.01-0.1 s−1. Electron backscattered diffraction results revealed that the dynamic restoration mechanism in the β phase field was dynamic recovery when the strain rate was as high as 10 s−1.