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Abstract Respiratory disease caused by coronavirus infection remains a global health crisis. Although several SARS-CoV-2-specific vaccines and direct-acting antivirals are available, their efficacy on emerging coronaviruses in the future, including SARS-CoV-2 variants, might be compromised. Host-targeting antivirals provide preventive and therapeutic strategies to overcome resistance and manage future outbreak of emerging coronaviruses. Cathepsin L (CTSL) and calpain-1 (CAPN1) are host cysteine proteases which play crucial roles in coronaviral entrance into cells and infection-related immune response. Here, two peptidomimetic α-ketoamide compounds, 14a and 14b, were identified as potent dual target inhibitors against CTSL and CAPN1. The X-ray crystal structures of human CTSL and CAPN1 in complex with 14a and 14b revealed the covalent binding of α-ketoamide groups of 14a and 14b to C25 of CTSL and C115 of CAPN1. Both showed potent and broad-spectrum anticoronaviral activities in vitro, and it is worth noting that they exhibited low nanomolar potency against SARS-CoV-2 and its variants of concern (VOCs) with EC50 values ranging from 0.80 to 161.7 nM in various cells. Preliminary mechanistic exploration indicated that they exhibited anticoronaviral activity through blocking viral entrance. Moreover, 14a and 14b exhibited good oral pharmacokinetic properties in mice, rats and dogs, and favorable safety in mice. In addition, both 14a and 14b treatments demonstrated potent antiviral potency against SARS-CoV-2 XBB 1.16 variant infection in a K18-hACE2 transgenic mouse model. And 14b also showed effective antiviral activity against HCoV-OC43 infection in a mouse model with a final survival rate of 60%. Further evaluation showed that 14a and 14b exhibited excellent anti-inflammatory effects in Raw 264.7 mouse macrophages and in mice with acute pneumonia. Taken together, these results suggested that 14a and 14b are promising drug candidates, providing novel insight into developing pan-coronavirus inhibitors with antiviral and anti-inflammatory properties.

The quick and accurate characterization of commercial electrochemical double-layer capacitor (EDLC) cells, especially their capacitance and direct-current equivalent series internal resistance (DCESR), is of great significance for the design, maintenance, and monitoring of EDLCs used in areas of energy, sensors, electric power, construction machinery, rail transit, automobile transportation, and military. In this study, the capacitance and DCESR of three commercial EDLC cells with similar performance were determined and compared by following the three commonly-used standards of IEC 62391, Maxwell, and QC/T741-2014, which are significantly different in test procedures and calculation methods. The analysis of the test procedures and results demonstrated that the IEC 62391 standard has the disadvantages of a large testing current, long testing time, and a complex and inaccurate DCESR calculation, whereas the Maxwell standard has the disadvantages of a large testing current, a small capacitance, and large DCESR testing results, and furthermore the QC/T 741 standard has the disadvantages of a high resolution requirement for the equipment and small DCESR results. Therefore, an improved method was proposed to determine the capacitance and DCESR of EDLC cells by short-time constant voltage charging and discharging interruption methods, respectively, with the advantages of high accuracy, low equipment requirements, short testing time, and the easy calculation of DCESR over the original three standards.

The mechanisms underlying differential chemotherapeutic response to 5-fluorouracil are not fully known. Here, the authors show that ABDH5 regulates sensitivity to 5-fluorouracil in colorectal cancer by regulating lysosome function.

The state-of-health (SOH) is a critical parameter to determine the degradation degree of lithium-ion batteries, thus plays an important part in energy management problems of electric vehicles (EVs). Due to the estimation dispersion of health indicators, it is difficult to monitor conveniently and robustly the SOH of on-board batteries. In this paper, a health monitoring method for the application of battery management system (BMS) has been presented to solve this issue. First of all, the necessity of multiple indicators (MIs) is demonstrated through the analysis of estimation dispersion of single indicator (SI), and three health indicators are extracted from actual operating conditions of EVs. After that, the mixed membership function (MMF) according to fuzzy logic theory is applied to integrate the estimation effects of different health indicators. Then, the analytic hierarchy process (AHP) using dispersion information of health indicators is introduced to calculate the weight coefficient of each indicator. Finally, the performance and robustness of the proposed method have been verified by numerous experiments. The results indicate the average estimation errors of five tested batteries are less than 3%, and the influences of estimation dispersion are largely eliminated when compared with the SI-based and other MIs-based methods.

We, the authors, wish to make the following corrections to our paper [...]

The distributed attitude synchronization control problem for spacecraft formation flying subject to limited energy and computational resources is addressed based on event-triggered mechanism. Firstly, a distributed event-driven controller is designed to achieve attitude coordination with the limitation of energy and computing resources. Under the proposed control strategy, the controller is only updated at the event triggering instants, which effectively reduces the update frequency. Subsequently, an event-triggered strategy is developed to further decrease energy consumption and the amount of computation. The proposed event-triggered function only requires the latest state information about its neighbors, implying that the trigger threshold does not need to be calculated continuously. It is shown that the triggering interval between two successive events is strictly positive, showing that the control system has no Zeno phenomenon. Moreover, the update frequency of the proposed controller can be reduced by more than 90% compared to the update frequency of the corresponding time-driven controller with an update frequency of 10 Hz by choosing appropriate control parameters and the control system can still achieve high-precision convergence. Finally, the effectiveness of the constructed control scheme is verified by numerical simulations.

The target recognition and location based on the vision sensor is a kind of more intuitive and effective method. The paper designs a human mobile robot and the monocular PTZ camera fixed on the differential driver of the mobile robot for the target recognition and localization. The camera parameters are calibrated using the Zhang Zhengyou calibration method; target recognition is based on the combination of the color and the edge detection. First, the objects with the same color are extracted by the color recognition method (by setting an appropriate threshold value for the HSV color space of the acquired image). Then the target is further extracted by the edge detection (by Hough circle transformation); target location is based on the Similar Triangle Principle because the PTZ camera has pitch, tilt, and zoom characteristics and the monocular vision sensor of the camera with different pitching angles is used to measure the distance between the robot and the target. According to the characteristics of the monocular PTZ camera the mobile robot realizes the target localization and tracking. The simulation and experimental results demonstrate that the mobile robot shows better target recognition and localization in mobile tracking target process and proves the effectiveness of the method.

Objective: Qingzaojiufei decoction (QD) is an empirical herbal formula from traditional Chinese medicine that is used for the treatment of lung-related diseases. However, the effect of QD on the growth of lung tumor cells has not been investigated. The aim of this study was to examine the antitumor activity of QD in Lewis lung carcinomas (LLC) in vivo and in vitro, and to elucidate the underlying mechanisms. Methods: The LLC cells were used to assess the antitumor activity of QD by Cell Counting Kit-8 assay in vitro. In vivo, mice were randomly assigned to 5 groups (n = 10/group): the model control (MC) group was intragastrically administered physiological saline (0.9% NaCl) twice daily from day 2 after tumor implantation for 2 weeks. The QD groups were intragastrically administered QD twice daily from 2 weeks before to 2 weeks after tumor implantation for 4 weeks. The mRNA levels were detected by quantitative polymerase chain reaction, the proteins expression was determined by immunohistochemistry or western blotting. Results: Compared with the model group, QD showed inhibition of proliferation of LLC cells and reductions in tumor weight and proliferating cell nuclear antigen protein expression. Furthermore, QD up-regulated p53 mRNA expression, and downregulated c-myc and Bcl-2 mRNA expression, while MMP-9, VEGF, and VEGFR protein expression was suppressed. Phosphorylated ERK1/2 levels were also reduced by QD in a dose-dependent manner. Conclusion: Our findings suggest that QD inhibited lung tumor growth and proliferation, by activation of tumor suppressor genes, inactivation of oncogenes, suppressing the potential for invasion and metastasis, and attenuating angiogenesis. The ERK/VEGF/MMPs signaling pathways may play an important role in QD-induced inhibition of malignant tumor cell proliferation.

TW-37 is a novel, potent and non-peptide Bcl-2 small-molecule inhibitor. Its activity in colorectal cancer (CRC) cells is studied. In both HCT-116 cells and primary human colon cancer cells, treatment with TW-37 at only nM concentration efficiently inhibited cell survival and proliferation. TW-37 also induced caspase-3/9 and apoptosis activation in CRC cells. Feedback autophagy activation was observed in TW-37-treated CRC cells. Reversely pharmacological autophagy inhibition or Beclin-1 knockdown by targeted-shRNA potentiated TW-37-induced apoptosis and killing of CRC cells. In vivo, intravenous injection of TW-37 inhibited HCT-116 tumor growth in mice. TW-37's anti-tumor activity was further potentiated against Beclin-1-silenced HCT-116 tumors. Together, targeting Bcl-2 family protein by TW-37 efficiently inhibits CRC cell growth in vitro and in vivo. Inhibition of feedback autophagy activation could further sensitize TW-37.