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The presence of multiple immunosuppressive targets and insufficient activation and infiltration of cytotoxic T lymphocytes (CTLs) allow tumor cells to escape immune surveillance and disable anti-PD-1/PD-L1 immunotherapy. Nanobiotechnology-engineered autologous tumor vaccines (ATVs) that were camouflaged by tumor cell membrane (TCM) were designed to activate and facilitate CTLs infiltration for killing the unprotected lung tumor cells, consequently realizing the sequential immunotherapy. PDE5 was firstly screened out as a new immunosuppressive target of lung cancer in clinical practice. Immediately afterwards, phosphodiesterase-5 (PDE5) and programmed cell death 1 ligand 1 (PD-L1) dual-target co-inhibition was proposed to unfreeze the immunosuppressive microenvironment of NSCLC. Systematic studies validated that this ATVs-unlocked sequential immunotherapy after co-encapsulating PDE5 inhibitor and NO donor (i.e., l -arginine) exerted robust anti-tumor effects through increasing inducible nitric oxide synthase (iNOS) expression, blockading PDE5 pathway and activating systematic immune responses, which synergistically eradicated local and abscopal lung cancers in either orthotopic or subcutaneous models. The pluripotent ATVs that enable PDE5 inhibition and sequential immunotherapy provide a new avenue to mitigate immunosuppressive microenvironment and magnify anti-PD-1/PD-L1 immunotherapy.

Background: Macrophages play an important role in renal ischemia reperfusion injury, but the functional changes of macrophages under hypoxia/reoxygenation and the related mechanism are unclear and need to be further clarified. Methods: The effects of hypoxia/reoxygenation on functional characteristics of RAW264.7 macrophages were analyzed through the protein expression detection of pro-inflammatory factors TNF-α and CD80, anti-inflammatory factors ARG-1 and CD206. The functional implications of C-X3-C motif chemokine receptor 1(CX3CR1) down-regulation in hypoxic macrophages were explored using small interfering RNA technology. Significance was assessed by the parametric t-test or nonparametric Mann–Whitney test for two group comparisons, and a one-way ANOVA or the Kruskal–Wallis test for multiple group comparisons. Results: Hypoxia/reoxygenation significantly increased the protein expression of M1-related pro-inflammatory factors TNF-α, CD80 and chemokine C-X3-C motif chemokine ligand 1 (CX3CL1)/CX3CR1 and inhibited the protein expression of M2-related anti-inflammatory factors ARG-1 and CD206 in a time-dependent manner in RAW264.7 cells. However, the silencing of CX3CR1 in RAW264.7 cells using specific CX3CR1-siRNA, significantly attenuated the increase in protein expression of TNF-α (P

With the growing prominence of privacy protection issues in big data, artificial intelligence and blockchain, secure multi-party computation has become a research hotspot. Confidentially computing the set problem is an important branch of secure multi-party computation. The relationship between an integer and an interval is the most basic problem in the study of computing set problems. At present, there are many research solutions for secure multi-party computation against malicious adversaries. In this paper, we analyze some possible malicious attacks in the protocol of determining an integer and an interval relationship under the semi-honest model. By using the Goldwasser–Micali encryption scheme, Paillier encryption algorithm, zero-knowledge proof and cut-choose method, we design the secret judgment protocol of an integer and an interval relationship under the malicious model. Finally, an ideal-practical example proof method is used to prove that the protocol is secure under the malicious model. Compared with the existing schemes, it not only keeps good efficiency, but also can resist the attack of malicious opponents, and the protocol is more fair. The scheme has a wide application prospect.

Pressure relief borehole is one of the most effective methods to treat coal burst in deep-buried coal seams. However, due to the large amount of randomly distributed fractures in the coal body and the varying stress environments in underground coal mines, there is no practical method to assess relief boreholes by far, which brings problems for borehole design and construction. This study focuses on the assessment of relief boreholes in a single driving entry wherein the impact of mining panels on relief boreholes is eliminated. A practical method, focusing on field monitoring of borehole deformation with a new device, is developed to evaluate the single driving entry’s relief boreholes. This method is applied to a Chinese coal mine. The application results showed that the convergence process of the boreholes showed a three-phase characteristic. Phase one involves the fastest deformation, reaching up to 8% in the first 3 to 4 days. Phase two lasts longer and converges more, reaching up to 30% in 4 months. Phase three stays balanced until the excavating face moves. The three-phase characteristic indicates that a large diameter of the borehole ensures relief efficiency because the borehole provides adequate space for deformation throughout its life span. In addition, it is verified that long boreholes and slow footage improve relief efficiency by providing adequate time for the boreholes to work. The application proposes that boreholes in the test coal mine need to be drilled larger and longer for optimization.

Quantifying the aggregation patterns of urban population, economic activities, and land use are essential for understanding compact development, but little is known about the difference among the distribution characteristics and how the built environment influences urban aggregation. In this study, five elements are collected in Wuhan, China, namely population density, floor area ratio, business POIs, road network and built-up area as the representative of urban population, economic activities and land use. An inverse S-shape function is employed to fit the elements’ macro distribution. An aggregation degree index is proposed to measure the aggregation level of urban elements. The kernel density estimation is used to identify the aggregation patterns. The spatial regression model is used to identify the built environment factors influencing the spatial distribution of urban elements. Results indicates that all urban elements decay outward from the city center in an inverse S-shape manner. The business Point-of-Interest (POI) density and population density are highly aggregated; floor area ratio and road density are moderately aggregated, whereas the built-up density is poorly aggregated. Three types of spatial aggregation patterns are identified: a point-shaped pattern, an axial pattern and a planar pattern. The spatial regression modeling shows that the built environment is associated with the distribution of the urban population, economic activities and land use. Destination accessibility factors, transit accessibility factors and land use diversity factors shape the distribution of the business POI density, floor area ratio and road density. Design factors are positively associated with population density, floor area ratio and built-up density. Future planning should consider the varying spatial concentration of urban population, economic activities and land use as well as their relationships with built environment attributes. Results of this study will provide a systematic understanding of aggregation of urban land use, population, and economic activities in megacities as well as some suggestions for planning and compact development.

BACKGROUND Respiratory tract infections in the elderly are difficult to cure and can easily recur, thereby posing a great threat to patient prognosis and quality of life. AIM To investigate the therapeutic effects of different antibiotics in elderly patients with respiratory tract infection. METHODS Seventy-four elderly patients with respiratory tract infection were randomly allocated to a study (n = 37; treated with cefoperazone sodium/sulbactam sodium) or control (n = 37; treated with piperacillin sodium/tazobactam sodium on the basis of routine symptomatic support) group. Both groups were treated for 7 d. Time to symptom relief (leukocyte recovery; body temperature recovery; cough and sputum disappearance; and rale disappearance time), treatment effect, and laboratory indexes [procalcitonin (PCT), C-reactive protein (CRP), white blood cell count (WBC), and neutrophil percentage (NE)] before and 7 d after treatment and the incidence of adverse reactions were assessed. RESULTS In the study group, the time to WBC normalization (6.79 ± 2.09 d), time to body temperature normalization (4.15 ± 1.08 d), time to disappearance of cough and sputum (6.19 ± 1.56 d), and time to disappearance of rales (6.68 ± 1.43 d) were shorter than those of the control group (8.89 ± 2.32 d, 5.81 ± 1.33 d, 8.77 ± 2.11 d, and 8.69 ± 2.12 d, respectively; P = 0.000). Total effective rate was higher in the study group (94.59% vs 75.68%, P = 0.022). Serum PCT (12.89 ± 3.96 μg/L), CRP (19.62 ± 6.44 mg/L), WBC (20.61 ± 6.38 × 109/L), and NE (86.14 ± 7.21%) levels of the study group before treatment were similar to those of the control group (14.05 ± 4.11 μg/L, 18.79 ± 5.96 mg/L, 21.21 ± 5.59 × 109/L, and 84.39 ± 6.95%, respectively) with no significant differences (P = 0.220, 0.567, 0.668, and 0.291, respectively). After 7 d of treatment, serum PCT, CRP, WBC, and NE levels in the two groups were lower than those before treatment. Serum PCT (2.01 ± 0.56 μg/L), CRP (3.11 ± 1.02 mg/L), WBC (5.10 ± 1.83 × 109/L), and NE (56.35 ± 7.17%) levels were lower in the study group than in the control group (3.29 ± 0.64 μg/L, 5.67 ± 1.23 mg/L, 8.13 ± 3.01 × 109/L, and 64.22 ± 8.08%, respectively; P = 0.000). There was no significant difference in the incidence of adverse reactions between the groups (7.50% vs 12.50%, P = 0.708). CONCLUSION Piperacillin sodium/tazobactam sodium is superior to cefoperazone sodium/ sulbactam sodium in the treatment of elderly patients with respiratory tract infection with a similar safety profile.

It is convenient to use the inelastic displacement ratio spectra and residual displacement ratio spectra to predict the maximum inelastic displacement and residual displacement of building structures based on linear elastic analysis directly. The prestressed concrete wall system with friction devices (PCW-FD system) can be simulated by single-degree-of-freedom (SDOF) model with self-centering behavior. To investigate the seismic performance of PCW-FD system, the SDOF models with fully and non-fully self-centering behavior are analyzed firstly, and it is concluded that the hysteresis parameters (strength reduction coefficient, post-yield stiffness coefficient, energy dissipation coefficient, and period) have significant influence on the seismic responses (such as constant relative strength inelastic displacement ratio, constant relative strength residual displacement ratio, maximum absolute acceleration, the hysteretic energy, and site classifications) during short period, and the trends of the seismic responses are similar at different site classifications. Then a large amount of the result data is summarized, and the constant relative strength inelastic displacement ratio spectra and the constant relative strength residual displacement ratio spectra with enough precision (the correlation coefficients are 0.957 and 0.947, respectively) are established by conducting regression analysis. Finally, the direct displacement–based seismic design method is improved and verified to be suitable for PCW-FD system.

This paper proposes an organic photodiode (OPD) image sensor based on indium zinc oxide (IZO) thin-film transistors (TFTs). The sensor array has a $256\times256$ pixel format with a $50~\mu \text{m}$ pixel size. The continuous OPD fabricated by the solution process is stacked vertically on the top of the IZO TFT backplane. A measurement system is built based on the readout IC driven by the field programmable gate array (FPGA). It is shown that the optical image can be successfully detected by the sensor array with good clarity and high quality. With a leakage current of the IZO TFT as low as $5\times 10^{\vphantom {D^{l}}-14}$ A and a dark current of OPD as low as $10^{-13}$ A, the total electronic noise is less than 683 e−.

The production of electricity is important, suitable and secure for human living, yet electricity is actually generated mainly from fossil fuels and nuclear energy, calling for renewable energies such as solar, wind and tidal renewable energies such as solar, wind and tidal. Solar energy is broadly harvested by various types of solar cells. Three-dimensional perovskite solar cell exhibits high power conversion efficiency of 25.2% with low stability, whereas two-dimensional perovskite solar cell exhibits better stability with moderate power conversion efficiency. Hence, we review two-dimensional perovskite solar cells fabricated with varying numbers of hybrid two-dimensional perovskite layers, organic cations, deposition techniques, the addition of additives and capping layers to improve power conversion efficiency with long-term better stability.

Objectives Cephalic arch stenosis (CAS) is a common cause that leads to the failure of hemodialysis arteriovenous fistulas (AVFs). Patients with CAS are primarily treated with fluoroscopy-guided angioplasty. Here, seven patients with de novo cephalic arch stenosis who underwent office-based UG-PTA were. Methods Retrospectively analyzed the total of 321 patients with AVF dysfunction in the nephrology departmnet between July 2017 and October 2018. Among them, seven patients with de novo CAS were included in this study and followed up every 2 months for more than a year. Results No significant complications were seen from the operations, and the primary patency rates at 6 and 12 months were found to be 100% and 42.8%, respectively. Conclusions The office-based UG-PTA is probably safe, effective, and feasible in the management of CAS and can be used as a substitute for fluoroscopy-guided PTA.

Introduction Secondhand smoke (SHS) exposure affects tobacco related health behaviors during adolescence and persists into adulthood. This study aimed to investigate the influence of SHS exposure on tobacco use among adolescents stratified by school and gender, and provide recommendations for controlling tobacco use in youth. Methods Through stratified random cluster sampling, 12278 selected students (aged 13-18 years) from schools in China were administered questionnaires. Multiple logistic regression was used to analyze whether SHS exposure would increase the smoking risk and susceptibility of adolescents. Results The prevalence of SHS exposure among the participating students was 74.8%. Adolescents exposed to SHS were at higher odds of being susceptible and currently smoking. Students with SHS exposure at both home and public places accounted for 36.6%, greatly increasing the current smoking risk and smoking susceptibility. Home SHS exposure had greater impact on the current tobacco use of boys (OR=2.13; 95% CI: 1.50-3.03) and junior school students (OR=4.67; 95% CI: 2.41-9.06). Exposure from public places increased the risk of current smoking in boys (OR=4.20; 95% CI: 2.31-7.65) and smoking susceptibility of vocational school students (OR=1.51; 95% CI: 1.07-2.15). Students with highlevel exposure to SHS had 2.25 times higher odds of e-cigarette use. Conclusions The prevalence of SHS exposure is still high among adolescents in China and is associated with increased risk for tobacco use regardless of gender and school level. Effective smoke-free strategies should be developed and strictly implemented. Boys and junior school students constitute vulnerable populations exposed to SHS at home.

In recent years, much interest in the study of Van der Waals heterostructures (vdWhs) has arisen. This has led to a significant amount of fundamental research being produced, from which novel optoelectronic applications have been established. By using first principles, we analyze the electronic structure of silicane/SnSe2 vdWhs in the response to an externally applied electric field and a normal strain. The results show that the silicane/SnSe2 vdWh acts as an indirect semiconductor when it is subjected to an applied electric field between −1 and 0.1 V/Å and becomes a metal in the 0.2 to 1 V/Å range. Significantly, the electronic band alignments of the silicane/SnSe2 vdWhs are modified from a type-II to a type-I when a field of −0.7 V/Å is applied. Furthermore, it is determined that the silicane/SnSe2 vdWhs appears to have a semiconductor-metal phase transition at a strain of −5%. Our results indicate that the silicane/SnSe2 vdWhs have the potential for applications in novel high-performance optoelectronic devices.

This study evaluates the impact of the anti-corruption campaign launched by President Xi since 2013 on coal mine mortality in China. Combining several unique provincial-level datasets on coal mines from 2004 to 2017, we find evidence that provinces with stronger exposure to the anti-corruption campaign have experienced a significantly larger decrease in coalmine death rates. This effect survives a vast array of robustness checks and also displays great heterogeneity. Further evidence suggests the campaign has led to fewer safety violations, more fixed investments and a decrease in profits accompanied by an increase in the costs of principal business in the coal mining industry. The above findings are most consistent with the interpretation that the campaign has made coal mining firms less likely to shirk on safety by curbing collusion between coal mines and local officials. We also rule out other channels such as intensified inspection and the change of employment composition in the industry.

Despite the great appeal of two-dimensional semiconductors for electronics and optoelectronics, to achieve the required charge carrier concentrations by means of chemical doping remains a challenge due to large defect ionization energies (IEs). Here, by decomposing the defect IEs into three parts based on ionization process, we propose a conceptual picture that the large defect IEs are caused by two effects of reduced dimensionality. While the quantum confinement effect makes the neutral single-electron point defect levels deep, the reduced screening effect leads to high energy cost for the electronic relaxation. The first-principles calculations for black phosphorus and MoS2 do demonstrate the general trend. Using BP monolayer either embedded into dielectric continuum or encapsulated between two hBN layers, we demonstrate the feasibility of increasing the screening to reduce the defect IEs. Our analysis is expected to help achieve effective carrier doping and open ways toward more extensive applications of 2D semiconductors.

Background The prognosis of patients with colorectal cancer and peritoneal metastasis (CRC-PM) after incomplete cytoreductive surgery (CRS) or palliative surgery is poor. Novel and effective therapies are urgently needed. This study aimed to assess the effects of palliative postoperative hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with CRC-PM. Methods This retrospective study included patients with CRC-PM at the First Affiliated Hospital of Xi’an Jiaotong University in 05/2014–05/2019. Observation indicators included overall survival (OS), ascites-free survival, peritoneal cancer index (PCI), and completeness of cytoreduction (CC). Kaplan-Meier survival curves and multivariable Cox regression models were used to determine the factors associated with OS and ascites-free survival. The ascites-specific quality of life (QoL) was measured using the Functional Assessment of Chronic Illness Therapy-Ascites Index (FACIT-AI). Results Eighty-two patients were included, including 37 and 45 in the HIPEC and non-HIPEC groups, respectively. Mean OS was 10.3±3.7 (95% CI 9.5–11.2) months. Multivariable Cox proportional hazard regression suggested that PCI (HR=6.086, 95% CI 3.187–11.620, P < 0.0001) was independently associated with OS. The degree of ascites (HR=2.059, 95% CI 1.412–3.005, P < 0.0001), PCI (HR=6.504, 95% CI 2.844–14.875, P < 0.0001), and HIPEC (HR=0.328, 95% CI 0.191–0.562, P < 0.0001) were independently associated with ascites-free survival. In patients with survival >6 months, postoperative ascites-specific QoL was significantly improved after HIPEC compared with the non-HIPEC group (P < 0.001). Oxaliplatin-based HIPEC significantly increased the rates of neutropenia and peripheral neurotoxicity (both P < 0.05). Conclusion These data indicate that postoperative oxaliplatin-based HIPEC might help increase ascites-free survival in CRC-PM patients after incomplete CRS or palliative surgery, with improved QoL after 6 months of follow-up.

Background Synovial sarcoma is an aggressive but chemosensitive soft-tissue tumor. We retrospectively analyzed the efficacy of perioperative chemotherapy for synovial sarcoma with data from the nationwide database, Bone and Soft Tissue Tumor Registry in Japan. Methods This study included 316 patients diagnosed with synovial sarcoma between 2006 and 2012. Oncologic outcomes were analyzed using a Cox-hazard regression model. Moreover, the effects of perioperative chemotherapy on outcomes were evaluated using a matched-pair analysis. The oncologic outcomes of patients who did or did not receive chemotherapy were compared (cx + and cx-). Results Multivariate analysis revealed significant correlations of age (over 40, hazard ratio [HR] = 0.61, p = 0.043), margin status (marginal resection, HR = 0.18, p p = 0.013 versus wide resection) with overall survival; surgical margin type (marginal resection, HR = 0.14, p = 0.001 and intralesional resection, HR = 0.09, p = 0.035 versus wide resection) with local recurrence; and postoperative local recurrence (HR = 0.30, p = 0.027) and surgical margin (marginal resection, HR = 0.31, p = 0.023 versus wide resection) with distant relapse-free survival. Before propensity score matching, perioperative chemotherapy was mainly administered for young patients and patients with deeper tumor locations, larger tumors, more advanced-stage disease, and trunk location. The 3-year overall survival, local control, and distant relapse-free survival rates were 79.8%/89.3% (HR = 0.64, p = 0.114), 89.6%/93.0% (HR = 0.37, p = 0.171) and 71.4%/84.5% (HR = 0.60, p = 0.089) in the cx+/cx- groups, respectively. After propensity score matching, 152 patients were selected such that the patient demographics were nearly identical in both groups. The 3-year overall survival, local control, and distant relapse-free survival rates were 71.5%/86.0% (HR = 0.48, p = 0.055), 92.5%/93.3% (HR = 0.51, p = 0.436) and 68.4%/83.9% (HR = 0.47, p = 0.046) in the cx+/cx- groups, respectively. Conclusion This large-sample study indicated that the margin status and postoperative disease control were associated directly or indirectly with improved oncologic outcomes. However, the efficacy of perioperative chemotherapy for survival outcomes in synovial sarcoma patients was not proven in this Japanese database analysis.

Understanding the scaling characteristics in China is critical for perceiving the development process of rapidly urbanising countries. This paper conducts a comprehensive scaling analysis with quantitative assessment of a large number of diverse urban indicators of 275 Chinese cities. Our findings confirm that urban scaling laws can also be applied to rapidly urbanising China but demonstrate some unique features echoing its distinct urbanisation. Chinese urban population agglomeration results in more effective economic production but the economies of scale for infrastructure are less obvious. Some urban indicators associated with infrastructure and living facilities surprisingly scale super-linearly with urban population size, contrary to expected sublinear scaling behaviours. In developing countries, different-sized cities have diverse agglomeration, industrial and resource allocation advantages, which can be reflected by scaling exponents. We characterise these unique features in detail, exploring the spatial disparities and temporal evolution of scaling exponents ( β). Strong regional variations and differences are particularly pronounced in Northeast China and the Beijing-Tianjin-Hebei Urban Agglomeration. Scaling exponent variations over time reflect the temporal evolution of the urban system and measure the coordination and balance of urbanisation. Economic output was most efficient in 2009 and β of GDP was slightly greater than 1.15 in recent years. Urban land expansion has been accelerating since 2000 with β remaining around 0.85–0.90. The study of urban scaling in China is enlightening in elaborating the uniqueness and coordination of urban development in rapidly urbanising countries and provides support in formulating differentiated urban planning for different-sized cities to promote coordinated development.

This paper studies trajectory tracking control problem of quadrotor in the presence of external disturbances. A new control scheme integrating adaptive sliding mode disturbance observer (ASMDO) with backstepping funnel control is designed in both position loop and attitude loop. Adaptive sliding mode disturbance observer is utilized to estimate and compensate the external disturbances of quadrotor system, which relaxed the upper bound requirement in conventional sliding mode disturbance observer (SMDO) whilst adapting the gain of discontinuous term to a level as small as possible for consideration of chattering mitigation. The modified funnel function not only guarantees the dynamic quality in the tracking process but also avoids derivative operation of Euclidian norm of tracking error in the backstepping design. To guarantee stabilization of closed‐loop system, Lyapunov stability criterion is utilized in the overall controller design process. Finally, the effectiveness and superiority of the proposed scheme are illustrated by simulation results.

To study the hydrodynamic characteristics of a floating horizontal-axis tidal turbine (HATT) with rotation and surging motion under the condition of the free surface, a numerical simulation method based on CFD is established. The axial load coefficient and energy utilization ratio at different blade tip-immersion depths, surge periods and surge amplitudes were analyzed. The results show that the instantaneous values of the axial load coefficient and energy utilization ratio have obvious periodic fluctuations, and the fluctuation amplitude increases with the increase of the frequency and amplitude of surging. On this basis, the hydrodynamic load is divided into the hydrodynamic load in case of rotation only, the damping force and the additional mass force. The damping and additional mass coefficients are obtained based on the least square method. The damping coefficient of axial load coefficient changes little with the increase of surge frequency and amplitude, but increases with the increase of the blade tip-immersion depth. The damping coefficient of energy utilization ratio fluctuates periodically, and the fluctuation period is equal to the surge period. The research findings can provide relevant data for studying the coupling motion of floating tidal current energy device and control design of the output electricity.

The endocrine-disrupting activities of UV filters and synthetic progestin have raised concerns about their adverse risks. In this study, 208 urine samples were collected from Shanghai residents for the determination of seven benzophenones (BPs) and six synthetic progestins. The highest median concentration (6.21ng g-1 Cr) was observed in young adults (21-50 years), followed by a concentration of 3.86 ng g-1 Cr in elderly adults (over 50 years old), and the lowest median concentration (1.32 ng g-1 Cr) was found in children (8-11 years old). The detection rates of BP-3 and EE2 in adults were 97% and 82%, and in children were 31% and 24%, respectively. Synthetic progestin levels in Shanghai, China, were relatively low compared to other countries. And the urinary BPs level showed an increasing trend in Chinese in the past 5 years. The principal component analysis suggested that adults' exposure to BP-1 and BP-3 was related, which occurs through food or dermal absorption of these chemicals present in cosmetic products and coatings. And diet was an important exposure pathway for children exposed to BPs. Despite relatively high levels of synthetic progestin for female and obese, the total estimated daily intake (EDI) was still lower than acceptable daily intake adopted by America. In the Monte-Carlo analysis, the 95th percentile of hazard quotients (HQs) was 0.83, which indicated that potential health risks were appreciated in the studied population.

Electronic medical records (EMRs) are the most critical data in human health management. As in traditional centralized healthcare service systems (HSSs), user privacy security, EMRs data leakage, tampering, and island are some significant problems. However, blockchain is a promising technology to protect the privacy and realize cross-institutional data sharing for solving these problems. In this article, a novel peer-to-peer EMRs data management and trading system called healthchain has been proposed based on consortium blockchain technology. Through this distributed system, the patient can access their EMRs in different institutions freely, and the EMRs can be traded among different users conveniently. Then, to balance EMRs data supply and demand, we establish a Stackelberg pricing model to evaluate EMRs data providers and consumers’ interactions. The optimal unit price and data amounts can be found by applying the backward induction method, and the maximizing benefits of the participants can be obtained by achieving the Nash equilibrium in the proposed game. Moreover, security analysis shows the healthchain can provide secure EMRs management and trading, and the simulation results show that the proposed pricing model can help the healthchain achieve social welfare maximization.

Introduction: Although gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) with liver metastasis encompass a wide variety of clinical conditions with various prognosis, no statistical model for predicting the prognosis of these patients has been established. We sought to establish a more elaborative and individualized nomogram to predict survival of patients with liver-limited metastatic GEP-NENs. In addition, this nomogram was validated by both the Surveillance, Epidemiology, and End Results (SEER) database and a Chinese multicenter cohort. Methods: Patients diagnosed with GEP-NENs with liver-limited metastasis between 2010 and 2016 were identified from the SEER database. Kaplan-Meier survival analysis was performed to analyze survival outcomes. A nomogram was established based on the independent prognostic variables identified from univariate and multivariate Cox regression analyses. The nomogram was evaluated in both an internal validation SEER dataset and an external validation dataset composed of patients from the Chinese multicenter cohort. Results: A total of 1,474 patients from the SEER database and 192 patients from the multicenter cohort were included. Age, tumor size, differentiation, primary tumor resection, and liver metastasis resection were identified as independent prognostic factors by univariate and multivariate Cox analyses and were verified by Kaplan-Meier survival analysis (all p < 0.0001). A nomogram was developed and validated by calibration curves and areas under the curve of the external validation cohort, which showed good consistency and veracity in predicting overall survival. Conclusion: A nomogram was developed for the first time to predict the survival of patients with liver-limited metastases from GEP-NENs. Both internal and external validation demonstrated excellent discrimination and calibration of our nomogram. Based on this prognostic model, clinicians could develop more personalized treatment strategies and surveillance protocols.

CH₄–CO₂ replacement technology has broad application prospects in reducing CO₂ emission and developing natural gas hydrate (NGH) resources. It is of great significance to study the mechanism of CH₄–CO₂ replacement. In this paper, the effect of H₂O on CH₄–CO₂ displacement behavior is studied by molecular dynamics (MD) simulation and quantum mechanics calculation. The interactions between the host and guest in cages of CH₄ hydrate are calculated using the symmetry-adapted perturbation theory method. The contribution of physical components of binding energy can be determined. The result indicates that the electrostatic interaction of H₂O–H₂O and H₂O–gas is a key factor of the CH₄–CO₂ replacement mechanism. Additionally, the microconfigurations and microstructure properties are analyzed by MD simulation in the systems containing a gas layer (CO₂ or CH₄) and a CH₄ hydrate layer. The results showed that the movement and the arrangement of H₂O molecules influence the hydrate structure due to the interaction of H₂O–gas during the replacement process. The molecular simulation suggests that the change of electrostatic interaction with H₂O molecules could improve the CH₄–CO₂ replacement efficiency, which can be favorable for the investigation of CH₄ replacement technology in NGH with CO₂ injection.

A high-sensitivity and small-size pressure sensor based on dual fiber Bragg grating (FBG), a diaphragm and hinge-lever structure is proposed. Its measurement principle is described and simulation analysis is conducted. We compensate for temperature cross-sensitivity by using an additional FBG to accurately measure the ambient temperature. Sensing experiments indicate that the pressure sensitivity is 5.227 pm/kPa within the range of 0–1.0 MPa, which is three times greater than that of a single-diaphragm pressure sensor without a flexible hinge lever. The sensor is suitable for accurate and stable pressure measurement in oil and gas pipelines and similar environments.

The construction of hydrophobic nanochannel with hydrophilic sites for bionic devices to proximally mimick real bio-system is still challenging. Taking the advantages of MOF chemistry, a highly oriented CuTCPP thin film has been successfully reconstructed with ultra-thin nanosheets to produce abundant two-dimensional interstitial hydrophobic nanochannels with hydrophilic sites. Different from the classical active-layer material with proton transport in bulk, CuTCPP thin film represents a new type of active-layer with proton transport in nanochannel for bionic proton field-effect transistor (H+ -FETs). The resultant device can reversibly modulate the proton transport by varying the voltage on its gate electrode. Meanwhile, it shows the highest proton mobility of ≈9.5×10-3 cm2 V-1 s-1 and highest on-off ratio of 4.1 among all of the reported H+ -FETs. Our result demonstrates a powerful material design strategy for proximally mimicking the structure and properties of bio-systems and constructing bionic electrical devices.

AIMS Glomerular complement 3 (C3) deposition is often observed in renal biopsies of patients with IgA nephropathy (IgAN); however, the relationship between the intensity of C3 deposition and the long-term prognosis of IgAN has rarely been reported. In this retrospective study, we aimed to evaluate the prognostic value of glomerular C3 deposition for IgAN progression. METHODS AND RESULTS From June 2009 to June 2010, a total of 136 adult patients with IgAN were enrolled in the study. According to the intensity of glomerular C3 deposition, patients were divided into a glomerular C3high group (34 patients) and a glomerular C3low group (102 patients). The levels of clinical parameters, glomerular immune complexes, histopathological features, and serum cytokines of the two groups were compared. On the basis of an average of 105 months of follow-up, the predictive value of glomerular C3 deposition for IgAN progression was also investigated. Patients in the C3high group had more severe glomerular IgA, IgG, IgM, and complement factor H deposition, a higher percentage of mesangial hypercellularity (M1), and higher levels of segmental glomerulosclerosis (S1), tubular atrophy/interstitial fibrosis (T2), and crescents (C2) than those in the C3low group. Renal biopsies in the C3high group showed higher densities of interstitial inflammatory cells and higher levels of serum interferon-γ than those in the C3low group. Multivariate Cox regression analysis revealed that a higher intensity of glomerular C3 deposition remained as an independent predictor of serum creatinine doubling and end-stage renal disease. CONCLUSIONS A high intensity of glomerular C3 deposition is associated with the severity of renal lesions, and predicts long-term poor renal survival for IgAN patients.

A new external retrofitting sub-structure is proposed, namely, self-centering precast bolt-connected steel-plate reinforced concrete buckling-restrained-brace-frame (SC-PBSPC BRBF). Based on the 3D...

Metal-doping is an effective method to adjust the physical and chemical properties of semiconductor metal oxides. This work adopts a simple solvothermal method to synthesize Mo-doped tungsten oxide nanoparticles. The high-performance electrochromic films can be homogenously formed on ITO glass without post-annealing. Compared with pure WO3 films, the optimized Mo-doped WO3 films show improved electrochromic properties with significant optical contrast (68.3% at 633 nm), the short response time (6.3 s and 3.9 s for coloring and bleaching, respectively), and excellent coloration efficiency (107.2 cm2 C−1). The improved electrochromic behavior is mainly due to the increasing diffusion rate of Li+ in Mo-doped WO3 films (increased 20% than that of pure WO3 films). The porous surface of Mo-doped WO3 film shortens the diffusion path of Li+. Besides, Mo doping reduces the resistance and improves conductivity. Furthermore, 2at% Mo-doped WO3 films indicate satisfactory energy-storage properties (the specific capacitance is 73.8 F g−1), resulting from the enhanced electrochemical activity and fast electrical conductivity. This work presents a practical and economical way of developing high-performance active materials for bifunctional electrochromic devices.

Atopic dermatitis (AD) is a common disease clinically characterized by chronic recurrent eczematous lesions, dry skin, and pruritus. AD can negatively impact patients’ quality of life. The prevalence of AD in China has been increasing during the past few decades. Based on the most recent advances in the treatment of AD, we updated the 2014 version of the Guidelines for Diagnosis and Treatment of Atopic Dermatitis in China regarding the definition, epidemiology, pathogenesis, clinical classification, diagnosis, prevention, and treatment of AD.

Summary The relationship between gut microbial dysbiosis and acute or chronic kidney disease (CKD) is still unclear. Here, we show that oral administration of the probiotic Lactobacillus casei Zhang (L. casei Zhang) corrected bilateral renal ischemia-reperfusion (I/R)-induced gut microbial dysbiosis, alleviated kidney injury, and delayed its progression to CKD in mice. L. casei Zhang elevated the levels of short-chain fatty acids (SCFAs) and nicotinamide in the serum and kidney, resulting in reduced renal inflammation and damage to renal tubular epithelial cells. We also performed a 1-year phase 1 placebo-controlled study of oral L. casei Zhang use (Chinese clinical trial registry, ChiCTR-INR-17013952), which was well tolerated and slowed the decline of kidney function in individuals with stage 3–5 CKD. These results show that oral administration of L. casei Zhang, by altering SCFAs and nicotinamide metabolism, is a potential therapy to mitigate kidney injury and slow the progression of renal decline.

Aims/Introduction β‐Cell dysfunction is a hallmark of type 2 diabetes. In a previous pilot study, we identified an association between genetic variants within the human DACH1 gene and young‐onset type 2 diabetes. Here, we characterized the function of dachb, the only dach homologue to be expressed in the pancreas, in developing zebrafish embryos. Materials and Methods We injected one‐cell stage embryos with a dachb‐morpholino (MO) or with the dachb‐MO and dachb messenger ribonucleic acid, and determined the effect on the development of the pancreatic islet. We also carried out quantitative polymerase chain reaction and ribonucleic acid sequencing on the dachb‐MO group to determine the effect of dachb knockdown on gene expression. Results MO‐mediated dachb knockdown resulted in impaired islet cell development, with a significant decrease in both the β‐cell and islet cell numbers. This islet developmental defect was rescued when embryos were co‐injected with dachb‐MO and dachb messenger ribonucleic acid. Knockdown of dachb was associated with a significant downregulation of the β‐cell specific marker gene, insa, and the somatostatin cell marker, sst2, as well as regulators of pancreas development, ptf1a, neuroD, pax6a and nkx6.1, and the cell cycle gene, insm1a. Furthermore, ribonucleic sequencing analysis showed an upregulation of genes enriched in the forkhead box O and mitogen‐activated protein kinase signaling pathways in the dachb‐MO group, when compared with the control groups. Conclusions Together, our results suggest the possible role of dachb in islet development in zebrafish., Morpholino (MO)‐mediated knock‐down of dachb resulted in impaired islet cell development, with a significant decrease in both the β‐cell and islet cell numbers in zebrafish. Embryos co‐injected with dachb mRNA and dachb‐MO expressed a similar phenotype as the uninjected control groups, indicating rescue of the islet developmental defect. The studies highlight the role of dachb in islet development in zebrafish.

The urgent requirement of monitoring air pollution worldwide evokes intensive research interest in developing chemiresistive gas sensing techniques. To overcome the limits in sensitivity and selectivity of room temperature (RT) chemiresistive sensing materials, a new strategy using single-atom catalysts (SACs) via surface coordination is proposed. As a proof-of-concept, single Pd atoms on TiO2 (Pd1-TiO2) possess high efficiency in generating adsorbed O2- as well as high activity and selectivity in catalyzing CO oxidation at RT. As a result, Pd1-TiO2 shows record high sensitivity among the reported RT sensing materials, which is even comparable to those of the best materials working at high temperature. It also provides an approximately 1 order of magnitude lower limit of detection than the best CO sensing materials. Moreover, Pd1-TiO2 presents high selectivity toward 12 kinds of interference gases. This work not only paves a way to design high-performance RT gas sensing materials but also extends the application of SACs.

The original article has been corrected. It was written: Acknowledgments This work was supported by National Science and Technology Major Project (Project No. 2017-III-0007 and No. 2017-III-0002) and Youth Innovation Promotion Association, Chinese Academy of Science (No. 2019147). It is written: Acknowledgments This work was supported by National Science and Technology Major Project (Project No. 2017-III-0007-0032 and No. 2017-III-0002-0026) and Youth Innovation Promotion Association, Chinese Academy of Science (No. 2019147).

本工作通过溶剂热法制备了一种超稳定二维层状铜(I)富勒 烯配位聚合物材料. Cu-(η2-C60)配位作用和层间凹凸π⋅⋅⋅π相互作用 支撑C60分子排列形成倾斜六方面堆积((i-hfp))特点, 显著地改善了 材料的化学稳定性. 该材料表现出高性能可见光探测功能. 密度泛 函计算表明, 与六方紧密堆积和立方堆积的C60纳米材料类似, 其优 异的光探测功能主要来源于C60分子本身, 但是铜(I)的配位显著增 强了其对可见光的吸收效率, 改善了材料的可见光探测功能. 该工 作对于拓展富勒烯光电功能材料的种类具有重要意义.

Background South Asian (SA) individuals are more likely to develop end-stage renal disease (ESRD), but how chronic kidney disease (CKD) differs in relation to demographics, comorbidities and outcomes has not been studied. We aimed to study differences in SA individuals with CKD compared with White individuals. Methods This was an observational CKD cohort comparing SA with White individuals. Inclusion criteria were ≥18 years of age and two or more Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFRs 3 months apart. Individuals with ESRD at baseline were excluded. Baseline characteristics, including eGFR formulae [CKD-EPI and CKD-EPI-Pakistan (CKD-EPI-PK)], were compared. Analysis using competing risk regression for cardiovascular (CV) and ESRD events and Cox proportional hazard model for mortality was performed. Results From an adult population of 277 248 individuals, 17 248 individuals had CKD, of whom 1990 (11.5%) were of SA ethnicity. Age-adjusted prevalence of CKD was similar between ethnicities. SA individuals were more likely to be male, younger and socioeconomically deprived, and to have diabetes mellitus, CV disease and advanced CKD. Mean CKD-EPI-PK eGFR was 6.5 mL/min/1.73 m2 lower (41.1 versus 47.6, 95% confidence interval for difference 6.47–6.56) than for CKD-EPI. During 5 years of follow-up, 5109 (29.6%) individuals died, 2072 (12.0%) had a CV and 156 (0.90%) an ESRD event. Risk for SA individuals was higher for ESRD, similar to CV events and lower for mortality. Each 1 mL/min/1.73 m2 decrease in CKD-EPI-PK was associated with a 13.1% increased ESRD risk (adjusted subdistribution hazard ratio 0.869, 95% confidence interval 0.841–0.898). Conclusions SA individuals with CKD were younger and had more advanced disease than White individuals. Risk of ESRD was higher and CKD-EPI-PK was associated with ESRD risk in SA individuals. Specific CKD interventions, including the use of CKD-EPI-PK, should be considered in SA populations.

An opportunistic network is a special type of wireless mobile ad hoc network that does not require any infrastructure, does not have stable links between nodes, and relies on node encounters to complete data forwarding. The unbalanced energy consumption of ferry nodes in an opportunistic network leads to a sharp decline in network performance. Therefore, identifying the ferry node group plays an important role in improving the performance of the opportunistic network and extending its life. Existing research studies have been unable to accurately identify ferry node clusters in opportunistic networks. In order to solve this problem, the concepts of k-core and structural holes have been combined, and a new evaluation indicator, namely, ferry importance rank, has been proposed in this study for analyzing the dynamic importance of nodes in a network. Based on this, a ferry cluster identification model has been designed for accurately identifying the ferry node clusters. The results of the simulations conducted for verifying the performance of the proposed model show that the accuracy of the model to identify the ferry node clusters is 100%.

InP quantum dots (QDs) are considered as the most promising alternative to Cd-based QDs with lower toxicity, and emission spectrum tunability ranging from the visible to near-infrared region. Although high-quality fluorescent InP QDs have been successfully synthesized by several groups, the rigorous synthesis conditions hinder its practical use in display devices. In this work, for the first time, we introduce Zn2+ into the growth stage of the InP QDs to prepare an InP–In(Zn)P core, and then the as-grown InP–In(Zn)P cores were consecutively coated with typical double shells of inner ZnSe and outer ZnS. The final InP–In(Zn)P/ZnSe/ZnS core/shell/shell QDs exhibited a maximum photoluminescence (PL) quantum yield (QY) of 94.3% and have tunable emissions from yellow (569 nm) to red (630 nm), showing a potential application in display devices. Above all, compared with other related studies, the excellent PL properties were obtained in relatively milder conditions (ultimate vacuum level of 400 mTorr). The results of this study provide guidance for the commercial application of InP QDs as a viable alternative to Cd-based QDs.

Global warming has become an issue of increasing worldwide concern. At present, the most direct way to solve this problem is to control carbon emissions. In our paper, carbon tax policy is injected into a two-stage supply chain consisting of one manufacturer and two retailers. We establish six game models according to the relationship (competitive or cooperative) between the retailers and three power structures (manufacturer Stackelberg (MS), retailer Stackelberg (RS), and vertical Nash (VN)) between the two retailers and the manufacturer. We then adopt the inverse induction method to derive optimal pricing decisions for each model. Optimal profits for supply chain members are obtained. Finally, we analyse: i) the effects of competition and cooperation between the two retailers on equilibrium results; ii) the effects of the three possible power structures existing between the manufacturer and the two retailers on equilibrium results; and especially iii) the effect of the carbon tax rate on pricing decision and the profits of the supply chain. We find that the different power structure and the horizontal relationship between the two retailers have important influence on equilibrium results. Further, the change of carbon tax rate have different influence on pricing under the different power structure and the horizontal relationship between the two retailers. When the government adjusts the carbon tax rate, it should fully consider the different power structure and the horizontal relationship for two-stage supply chain consisting of one manufacturer and two retailers. Although the implementation of the carbon tax policy reduces the corporate profits, it reduces the total carbon emission. The carbon tax policy is helpful to build an environment-friendly and resource-conserving society.

Background: Tremendous progress has been made in the treatment of colorectal cancer liver metastasis (CRCLM) in recent decades, and thousands of papers have been published. Therefore, we conducted a bibliometric analysis of articles related to CRCLM treatment to explore its evolution. Materials and Methods: The Clarivate Analytics Web of Science (WOS) Core Collection database was searched through June 2020 using terms related to CRCLM treatment. We analyzed the bibliographic information of the literature related to CRCLM treatment and explored the research topics to understand its evolution over time. Results: We identified 3436 records related to CRCLM treatment in the WOS database. The total number of times these documents were cited ranged 0-2352, and the years of publication spanned 1976-2020. The greatest numbers of articles were published in the United States, Japan, and France. Among institutions, Memorial Sloan-Kettering Cancer Center, MD Anderson Cancer Center, and Oslo University Hospital published the most articles. Regarding authors, Jarnagin WR, Adam R, Vauthey JN published the most articles. The research topics of these articles included systemic chemotherapy, molecular targeted therapy, the outcome of liver resection, prognosis prediction, hepatic artery infusion, radiofrequency ablation, and two-stage hepatectomy. Conclusion: Bibliometric analysis of studies related to CRCLM treatment can help doctors and researchers quickly understand the development trend in this field. These data emphasize the current management of patients with CRCLM, and they can potentially guide the direction of future research.

Introduction: Over the past 4 decades, the management of hepatocellular carcinoma (HCC) has changed dramatically. The publications that have had the most significant impact on HCC management have not been quantitatively analyzed. In this article, we analyzed the 100 most influential articles over the past 4 decades using bibliometric citation analysis to characterize the evolution in HCC treatment. Methods: The top-cited publications were identified and analyzed from the Clarivate Analytics Web of Science Core Collection database. Results: The 100 most cited articles were identified with an average of 738 citations (range: 349–6,799). There was an increase in the number of influential articles in the late 1990s, which was paralleled by an increase in reports focused on locoregional treatment of HCC. Most top 100 articles came from the USA (n = 35), followed by Italy (n = 28), mainland China (n = 26), and Japan (n = 24). The surgical management was the most studied topic (n = 33). The Annals of Surgery published the highest number of papers (n = 26) with 13,978 citations. While other 3 topics (surgical management, locoregional treatment, and outcome prediction) declined among publications beginning in the 2000s, there was an emergence of highly cited papers on targeted drugs and immune checkpoint inhibitors with a concomitant increase in the number of publications on systemic therapy. Conclusions: Based on bibliometric analysis of the literature over the last 40 years, a comprehensive analysis of the most historically significant HCC management articles highlighted the key contributions made to the evolution and advancement of this specialist field. The data should provide clinicians and researchers insight into future directions relative to the advancement of HCC management.

Background: Tertiary lymphoid organs (TLOs) occur after multiple chronic kidney injuries. interleukin-17A (IL-17A) has been reported to associate with the development of TLOs in inflammatory diseases. However, regulation of the renal TLOs and its clinical significance to the pathogenesis of chronic kidney injury are unknown. Methods: To evaluate the clinical significance and regulation of renal TLOs, we analyzed the progression of patients with kidney damage based on the existence and absence of TLOs in a larger multicenter cohort. We also blocked the recruitment of lymphocyte cells into the kidney by FTY720 (fingolimod) in vivo. Besides, we used aged IL-17A genetic knocked out mice and IL-17A-neutralizing antibody to explore the role of IL-17A in renal TLOs formation. Results: We demonstrated that renal TLOs of IgA nephropathy patients were associated with disease severity and were independent risk factors for renal progression after adjustment for age, sex, mean arterial pressure, proteinuria and, baseline eGFR and MEST-C score, especially in the early stage. Plasma levels of TLO-related chemokines CXCL13, CCL19, and CCL21 were higher in patients with renal TLOs. Inhibiting the formation of renal TLOs by FTY720 could reduce the intrarenal inflammation and fibrosis, and early intervention was found to be more effective. IL-17A was increased in renal TLOs models, and genetic depletion of IL-17A or treatment with anti-IL-17A antibody resulted in a marked reduction of the TLOs formation as well as alleviation of renal inflammation and fibrosis. Conclusion: These results indicate that TLOs are associated with the progression of kidney damage and regulated by IL-17A and may be effective targets for the treatment of kidney damage.

Background/Aims: Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease (NAFLD) characterized by hepatic steatosis, inflammation, hepatocellular injury, and fibrosis. We aimed to investigate the usefulness of a key biomarker, lipocalin-2 (LCN2), for the detection of NASH progression.Methods: A mouse NASH model was established using a high-fat diet and a high-sugar drinking water. Gene expression profile of the NASH model was analyzed using RNA sequencing. Moreover, 360 NAFLD patients (steatosis, 83; NASH, 277), 40 healthy individuals, and 87 patients with alcoholic fatty liver disease were recruited.Results: Inflammatory infiltration, focal necrosis in the leaflets, steatosis, and fibrosis were documented in the mouse liver. In total, 504 genes were differentially expressed in the livers of NASH mice, and showed significant functional enrichment in the inflammation-related category. Upregulated liver LCN2 was found to be significantly interactive with various interleukins and toll-like receptors. Serum LCN2 levels were significantly increased in NAFLD patients. Serum LCN2 levels were correlated with steatosis, intralobular inflammation, semiquantitative fibrosis score, and nonalcoholic fatty liver disease activity score. The area under the curve of serum LCN2 was 0.987 with a specificity of 100% and a sensitivity of 93.5% for NASH diagnosis, and 0.977 with almost the same specificity and sensitivity for steatosis.Conclusions: LCN2 might be involved in the transition from NAFL to NASH by mediating inflammation. Serum LCN2 levels might be a novel biomarker for the diagnosis of NASH.

Introduction: High risk of early death, especially contributed to cardiovascular disease, exists in patients who have chronic kidney disease (CKD). And the burden of cardiovascular disease is able to be lightened by an increase in omega-3 polyunsaturated fatty acid (omega-3 PUFA). A diet high in omega-3 PUFA in the general population is protective, although it is inconclusive about its beneficial role in the CKD population. Methods: From the 1999 to 2014 National Health and Nutrition Examination Surveys (NHANES), we can collect 2,990 participants who suffered from CKD, who were classified into 4 groups: Results: Over 8 years of a median follow-up, 864 deaths were recorded. The adjusted hazard ratios (95% confidence interval) for all-cause mortality of the diseased people with CKD in the 2nd (0.87–1.30 g/day), 3rd (0.87–1.30 g/day), and 4th (1.93–9.65 g/day) quartiles of dietary omega-3 PUFA were 0.94 (0.72, 1.23), 0.74 (0.54, 1.02), and 0.67 (0.48, 0.93), respectively, versus those with the lowest quartile of dietary omega-3 PUFA intake (p for trend = 0.011). Conclusion: There may be a inverse relation of dietary omega-3 PUFA intake and all-cause mortality in patients with CKD. Therefore, an increase of dietary omega-3 PUFA may be encouraged to be used clinically in patients with CKD.

Context As the terpenoid oxide extracted from Eucalyptus L. Herit (Myrtaceae), eucalyptol (EUC) has anti-inflammatory and antioxidant effects. Objective To evaluate the neuroprotective role of EUC in subarachnoid haemorrhage (SAH). Materials and methods Sprague-Dawley rats were divided into 4 groups: sham group, SAH group, SAH + vehicle group, and SAH + EUC group. SAH was induced by endovascular perforation. In SAH + EUC group, 100 mg/kg EUC was administrated intraperitoneally at 1 h before SAH and 30 min after SAH, respectively. Neurological deficits were examined by modified Neurological Severity Scores (mNSS). The brain edoema was evaluated by wet-dry method. Neuronal apoptosis was detected by Nissl staining. The expression of Bcl-2, cleaved caspase-3, phospho-NF-κB p65, ionised calcium-binding adapter molecule-1 (Iba-1), nuclear factor erythroid-2 (Nrf-2), and haem oxygenase 1 (HO-1) were measured by Western blot. Expression of pro-inflammatory cytokines was detected by qRT-PCR. Oxidative stress markers were also measured. Results EUC markedly relieved brain edoema (from 81.22% to 78.33%) and neurological deficits [from 16.28 to 9.28 (24 h); from 12.50 to 7.58 (48 h)]. EUC reduced neuronal apoptosis, microglial activation, and oxidative stress. EUC increased the expression of HO-1 (1.15-fold), Nrf2 (1.34-fold) and Bcl-2 (1.17-fold) in the rats’ brain tissue, and down-regulated the expressions of cleaved caspase-3 (41.09%), phospho-NF-κB p65 (14.38%) and pro-inflammatory cytokines [TNF-α (34.33%), IL-1β (50.40%) and IL-6 (59.13%)]. Discussion and Conclusion For the first time, this study confirms that EUC has neuroprotective effects against early brain injury after experimental SAH in rats.

Network pruning is a significant way to improve the practicability of convolution neural networks (CNNs) by removing the redundant structure of the network model. However, in most of the existing network pruning methods l1 or l2 regularisation is applied to parameter matrices and the manual selection of pruning threshold is difficult and labor‐intensive. A novel CNNs network pruning method via l0 regularisation is proposed, which adopts l0 regularisation to expand the saliency gap between neurons. A half‐quadratic splitting (HQS) based iterative algorithm is put forward to calculate the approximation solution of l0 regularisation, which makes the joint optimisation problem of regularisation term and training loss function can be solved by various gradient‐based algorithms. Meanwhile, a hyperparameters selection method is designed to make most of the hyperparameters in the algorithm can be determined by examining the pre‐trained model. The results of experiments on MNIST, Fashion‐MNIST and CIFAR100 show that the proposed method can provide a much clearer pruning threshold by widening the saliency gap, and achieve a similar or even better compression performance, compared with the state‐of‐the‐art studies.

Background Acute kidney injury (AKI) is an important complication of coronavirus disease 2019 (COVID-19), which could be caused by both systematic responses from multi-organ dysfunction and direct virus infection. While advanced evidence is needed regarding its clinical features and mechanisms. We aimed to describe two phenotypes of AKI as well as their risk factors and the association with mortality. Methods Consecutive hospitalized patients with COVID-19 in tertiary hospitals in Wuhan, China from 1 January 2020 to 23 March 2020 were included. Patients with AKI were classified as AKI-early and AKI-late according to the sequence of organ dysfunction (kidney as the first dysfunctional organ or not). Demographic and clinical features were compared between two AKI groups. Their risk factors and the associations with in-hospital mortality were analyzed. Results A total of 4020 cases with laboratory-confirmed COVID-19 were included and 285 (7.09%) of them were identified as AKI. Compared with patients with AKI-early, patients with AKI-late had significantly higher levels of systemic inflammatory markers. Both AKIs were associated with an increased risk of in-hospital mortality, with similar fully adjusted hazard ratios of 2.46 [95% confidence interval (CI) 1.35–4.49] for AKI-early and 3.09 (95% CI 2.17–4.40) for AKI-late. Only hypertension was independently associated with the risk of AKI-early. While age, history of chronic kidney disease and the levels of inflammatory biomarkers were associated with the risk of AKI-late. Conclusions AKI among patients with COVID-19 has two clinical phenotypes, which could be due to different mechanisms. Considering the increased risk for mortality for both phenotypes, monitoring for AKI should be emphasized during COVID-19.