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Abstract Objective To assess the immunization efficacy and incidence of adverse reactions after hepatitis B vaccination in children with thalassemia based on data from real-world studies. Methods A total of 625 children were recruited into this cross-sectional study. Subgroup analyses of different thalassemia types were performed using binary logistic regression, the factors affecting HBsAb levels were identified using multiple linear regression, and the dose-response relationship between the duration of immunization and seroconversion was explored using the restricted cubic spline (RCS) model to further assess the protective duration of the hepatitis B vaccine. Results HBsAb positivity in enrolled children was 87.3% in the thalassemia group and 81.4% in the control group. Multifactorial analysis revealed that the duration of immunization, age at completion of vaccination, and whether the first dose was delayed were significant factors influencing HBsAb levels in children (P

Abstract Faults play a crucial role in shaping the formation and damage patterns of landslides in the mountainous region, particularly in Qinling-Daba (Qinba) area in China. On 6 October 2022, following a 4-day rainfall event totaling 221.5 mm, a landslide occurred in Hanwang Town, Shaanxi Province. The left boundary of the landslide coincided with a fault, which influence the formation and movement development of the landslide. To further understand and quantified the formation process and damage mechanism of the landslide, a comprehensive study was conducted, incorporating field investigations, local rainfall data, and various methods including unmanned aerial vehicles (UAVs), numerical simulations, and laboratory test. The results indicate that fault dictate the formation of the Lijiaping landslide by influencing the mechanical strength of the rock mass and the catchment topography in the landslide area. Due to fault, the rock mass in the landslide area is high fragmentation, with a softening coefficient of about 0.52. Weathering resulted in numerous residual and slope sediments in the landslide area, providing ample material for the landslide. Meanwhile, the fault activity led to a wedge-shaped topography in the landslide area, with an average Terrain Wetness Index (TWI) of 3.43, significantly higher than the Hanwang Township average of 1.47. This creates a hydrogeological structure favorable for landslides. Numerical simulations revealed that the maximum velocity of the landslide reached 5.05 m/s and the maximum displacement was 53.18 m, both occurring in the central part of the landslide. These findings offer crucial scientific insights for understanding and preventing similar geological hazards.

ABSTRACTThis open-label, randomized, phase 3 study in China (V260-074; NCT04481191) evaluated the immunogenicity and safety of concomitant and staggered administration of three doses of an oral, live, pentavalent rotavirus vaccine (RV5) and three doses of an intramuscular, inactivated poliomyelitis vaccine (IPV) in 400 healthy infants. The primary objective was the non-inferiority of neutralizing antibody (nAb) responses in the concomitant- versus the staggered-use groups. Antibody responses were measured at baseline and 1-month post-dose 3 (PD3). Parents/legal guardians recorded adverse events for 30 or 15 d after study vaccinations in the concomitant-use or staggered-use groups, respectively. At PD3, >98% of participants seroconverted to all three poliovirus types, and the primary objective was met as lower bounds of the two-sided 95% CI for between-group difference in nAb seroconversion percentages ranged from − 4.3% to − 1.6%, for all poliovirus types, p

This study aimed to provide evidence for co-administration of the COVID-19 and EV71 vaccines in children aged 3 to 5 years. We conducted a phase 4, open-label, randomized, and controlled study. A total of 520 children were randomly allocated to two groups: Group C received the COVID-19 and EV71 vaccines simultaneously, while Group N received the two vaccines separately. The primary immunogenicity endpoints were the seroconversion rates of anti-SARS-CoV-2 and anti-EV71 antibodies 28 days after the second dose of each respective vaccine. Before vaccination, none of the participants was seropositive for anti-SARS-CoV-2 antibodies, and the baseline seropositivity for anti-EV71 antibodies was low (Group C: 14.86%; Group N: 17.83%). After completing full vaccination, the seroconversion rate of anti-SARS-CoV-2 antibodies reached 100% in both groups, while for anti-EV71 antibodies, the seroconversion rates were 97.99% in Group C and 98.70% in Group N. The lower limit of the 95% confidence interval for the difference in seroconversion rates between the two groups for both COVID-19 and EV71 vaccines met the predefined non-inferiority criteria. Six months post-vaccination, the antibody levels remained high for both vaccines, with the seropositive rates of anti-SARS-CoV-2 antibodies at 91.21% in Group C and 92.77% in Group N, and the seropositive rates of anti-EV71 antibodies at 99.16% in Group C and 99.15% in Group N. Safety analysis revealed a lower incidence of adverse reactions in Group C compared to Group N (28.85% vs 45.56%), primarily solicited. Co-administration of the COVID-19 and EV71 vaccines demonstrated a positive safety profile and non-inferior immune responses.Trial registration Number NCT04993365 (ClinicalTrials.gov).

Cattle farming is an important part of the global livestock industry, and cattle body size is the key indicator of livestock growth. However, traditional manual methods for measuring body sizes are not only time-consuming and labor-intensive but also incur significant costs. Meanwhile, automatic measurement techniques are prone to being affected by environmental conditions and the standing postures of livestock. To overcome these challenges, this study proposes a multi-view fusion-driven automatic measurement system for full-attitude cattle body measurements. Outdoors in natural light, three Zed2 cameras were installed covering different views of the channel. Multiple images, including RGB images, depth images, and point clouds, were automatically acquired from multiple views using the YOLOv8n algorithm. The point clouds from different views undergo multiple denoising to become local point clouds of the cattle body. The local point clouds are coarsely and finely aligned to become a complete point cloud of the cattle body. After detecting the 2D key points on the RGB image created by the YOLOv8x-pose algorithm, the 2D key points are mapped onto the 3D cattle body by combining the internal parameters of the camera and the depth values of the corresponding pixels of the depth map. Based on the mapped 3D key points, the body sizes of cows in different poses are automatically measured, including height, length, abdominal circumference, and chest circumference. In addition, support vector machines and Bézier curves are employed to rectify the missing and deformed circumference body sizes caused by environmental effects. The automatic body measurement system measured the height, length, abdominal circumference, and chest circumference of 47 Huaxi Beef Cattle, a breed native to China, and compared the results with manual measurements. The average relative errors were 2.32%, 2.27%, 3.67%, and 5.22%, respectively, when compared with manual measurements, demonstrating the feasibility and accuracy of the system.

The geological hazards of landslides in Hanwang Town, Ziyang County, Ankang City, Shaanxi Province, have emerged. Yet, the current understanding of the spatial distribution characteristics and influencing factors of landslides in this area remains unclear. Combining the results of remote sensing interpretation and field investigation, seven influencing factors, namely, elevation, slope direction, slope gradient, distance from rivers, distance from faults, engineering geologic lithology, and distance from roads, are selected for the study. The distribution characteristics of landslides in each influencing factor and the influence of the resolution of the Digital Elevation Model (DEM) on the results are statistically and analytically analyzed. Furthermore, two high-risk landslides within the study area were subjected to comprehensive analysis, integrating the findings from drilling and other field investigations in order to examine their deformation mechanisms. Based on this analysis, the following conclusions were derived: (1) 34 landslides in the study area, mainly small earth landslides, with a distribution density of 0.42/km2, threatening 414 people and property of about 55.87 million Yuan. (2)The landslides in the study area easily occur in the

To monitor the moisture content of agricultural products in the drying process in real time, this study applied a model combining multi-sensor fusion and convolutional neural network (CNN) to moisture content online detection. This study built a multi-sensor data acquisition platform and established a CNN prediction model with the raw monitoring data of load sensor, air velocity sensor, temperature sensor, and the tray position as input and the weight of the material as output. The model’s predictive performance was compared with that of the linear partial least squares regression (PLSR) and nonlinear support vector machine (SVM) models. A moisture content online detection system was established based on this model. Results of the model performance comparison showed that the CNN prediction model had the optimal prediction effect, with the determination coefficient (R2) and root mean square error (RMSE) of 0.9989 and 6.9, respectively, which were significantly better than those of the other two models. Results of validation experiments showed that the detection system met the requirements of moisture content online detection in the drying process of agricultural products. The R2 and RMSE were 0.9901 and 1.47, respectively, indicating the good performance of the model combining multi-sensor fusion and CNN in moisture content online detection for agricultural products in the drying process. The moisture content online detection system established in this study is of great significance for researching new drying processes and realizing the intelligent development of drying equipment. It also provides a reference for online detection of other indexes in the drying process of agricultural products.

High-temperature wireless sensing is crucial for monitoring combustion chambers and turbine stators in aeroengines, where surface temperatures can reach up to 1200 °C. Surface Acoustic Wave (SAW) temperature sensors are an excellent choice for these measurements. However, at extreme temperatures, they face issues such as agglomeration and recrystallization of electrodes, leading to loss of conductivity and reduced quality factor, hindering effective wireless signal transmission. This study develops an LGS SAW sensor with a Pt-10%Rh/Zr/Pt-10%Rh/Zr/Pt-10%Rh/Zr multilayer composite electrode structure to address these challenges. We demonstrate that the sensor can achieve wireless temperature measurements from room temperature to 1200 °C with an accuracy of 1.59%. The composite electrodes excite a quasi-shear wave on the LGS substrate, maintaining a Q-factor of 3526 at room temperature, providing an initial assurance for the strength of the wireless interrogation echo signal. The sensor operates stably for 2.18 h at 1200 °C before adhesion loss between the composite electrode and the substrate causes a sudden increase in resonant frequency. This study highlights the durability of the proposed electrode materials and structure at extreme temperatures and suggests future research to improve adhesion and extend the sensor’s lifespan, thereby enhancing the reliability and effectiveness of high-temperature wireless sensing in aerospace applications.

A Kalman filter fusion algorithm was proposed, and an online monitoring system was developed for real-time monitoring of the moisture content of materials in an air-impingement dryer. The Kalman filter algorithm was used to estimate the optimal state of the original detection values of the weighting sensor and air velocity sensor. A backpropagation (BP) neural network fusion model was established, where the weight detection value, elastic substrate temperature, air velocity, and impingement distance were considered inputs and the real weight of the material was the output. The optimal topology of the BP neural network was selected, and the initial weights and thresholds of the BP neural network were optimized using a genetic algorithm. The coefficient of determination (R2) and root mean square error (RMSE) of the optimized BP neural network fusion model were 0.9995 and 4.9, respectively. The Kalman filter fusion algorithm, which can realize online monitoring of moisture content, was established using the Kalman filter algorithm and fusion model. Moreover, an online monitoring system for material moisture content was developed, validation experiments were carried out, and the R2 and RMSE of the nine sets of validation experiments were 0.9963 and 0.78, respectively. The monitoring system satisfied the requirements of material moisture content detection accuracy in the drying process. The developed monitoring system is greatly important for improving the automation level of the drying equipment for fruits and vegetables. The proposed Kalman filter fusion algorithm also provides a reference for other multifactor fusion detection.

ABSTRACT Host innate immunity is an important defense line against virus infection and is precisely regulated by various factors. Studying the mechanism of virus-host interaction is essential to developing novel antivirals. Being one of the key host natural antiviral responses, host small non-coding RNAs (miRNAs) possess promising antiviral potential worthy of study. Herein, we found that miR-26a exerted broad-spectrum antiviral effect against multiple viruses, e.g., Hepatitis E virus, Vesicular Stomatitis Virus, and Sendai Virus. Mechanistically, miR-26a specifically targets 3′UTR of mRNA to inhibit USP15 expression. USP15 interacted directly with RIG-I to deubiquitinate K63-linked RIG-I, thus negatively regulating type I interferon (IFN) signaling. Consequently, miR-26a, by downregulating USP15, promotes K63 ubiquitination of RIG-I to enhance type I IFN responses, resulting in an active antiviral state against virus infection. Intriguingly, the activation of type I IFN responses could suppress miR-26a expression, serving as an intrinsic negative feedback loop to avoid dysregulated signal activation. Hence, the broad-spectrum antiviral effects of miR-26a and its mode-of-action enriched the interaction networks between miRNAs and innate immunity, providing insights for the development of broad-spectrum antivirals against viral infection. IMPORTANCE miR-26a serves as a potent positive regulator of type I interferon (IFN) responses. By inhibiting USP15 expression, miR-26a promotes RIG-I K63-ubiquitination to enhance type I IFN responses, resulting in an active antiviral state against viruses. Being an intricate regulatory network, the activation of type I IFN responses could in turn suppress miR-26a expression to avoid the disordered activation that might result in the so-called “type I interferonopathy.” The knowledge gained would be essential for the development of novel antiviral strategies against viral infection.

Background As pregnant women are excluded from clinical trials of inactivated SARS-CoV-2 vaccines, it is important to assess the immune response in women receiving the vaccination while unknowingly pregnant. Methods In a multicenter cross-sectional study, we enrolled 873 pregnant women aged 18-45 years. Serum antibody levels induced by inactivated vaccines were determined. Adverse events were collected by self-reported survey after vaccination. Logistic regression model and restricted cubic spline model were used to investigate the association of factors with antibody positivity. Results As the doses of the vaccine increase, neutralizing antibody (NAb) positivity was 98.3%, 39.5%, and 9.5% in pregnant women, respectively. The dose of vaccine and duration since vaccination were associated with NAb positivity. The OR of two and three doses of vaccines were 7.20 and 458.33 (P

Low velocity impacts may cause damages to the composite material. Piezoelectric transducers can be mounted onto the plate surface to monitor the impact by recording the impact induced guided waves. In this study, an impact localization algorithm based on 1D convolutional neural network is proposed. To test the effectiveness of the proposed algorithm, 4 PZTs were glued to a composite plate to monitor a region of 200 mm × 200 mm, and an impact experiment was conducted by dropping a glass ball at 117 different locations on the plate. The time-domain guided wave signals obtained by 4 PZTs were used as input to the 1D convolutional neural network. The output of the network was the coordinates of impact. The trained network was afterwards applied to locate impacts at unseen locations, and the mean localization error is 15.2 mm.

Continuous monitoring of vital signs based on advanced sensing technologies has attracted extensive attention due to the ravages of COVID-19. A maintenance-free and low-cost passive wireless sensing system based on surface acoustic wave (SAW) device can be used to continuously monitor temperature. However, the current SAW-based passive sensing system is mostly designed at a low frequency around 433 MHz, which leads to the relatively large size of SAW devices and antenna, hindering their application in wearable devices. In this paper, SAW devices with a resonant frequency distributed in the 870 MHz to 960 MHz range are rationally designed and fabricated. Based on the finite-element method (FEM) and coupling-of-modes (COM) model, the device parameters, including interdigital transducer (IDT) pairs, aperture size, and reflector pairs, are systematically optimized, and the theoretical and experimental results show high consistency. Finally, SAW temperature sensors with a quality factor greater than 2200 are obtained for real-time temperature monitoring ranging from 20 to 50 °C. Benefitting from the higher operating frequency, the size of the sensing system can be reduced for human body temperature monitoring, showing its potential to be used as a wearable monitoring device in the future.

In this paper, the effects on drying time (Y1), the color difference (Y2), unit energy consumption (Y3), polysaccharide content (Y4), rehydration ratio (Y5), and allantoin content (Y6) of yam slices were investigated under different drying temperatures (50–70 °C), slice thicknesses (2–10 mm), and radiation distances (80–160 mm). The optimal drying conditions were determined by applying the BP neural network wolf algorithm (GWO) model based on response surface methodology (RMS). All the above indices were significantly affected by drying conditions (p < 0.05). The drying rate and effective water diffusion coefficient of yam slices accelerated with increasing temperature and decreasing slice thickness and radiation distance. The selection of lower temperature and slice thickness helped reduce the energy consumption and color difference. The polysaccharide content increased and then decreased with drying temperature, slice thickness, and radiation distance, and it was highest at 60 °C, 6 mm, and 120 mm. At 60 °C, lower slice thickness and radiation distance favored the retention of allantoin content. Under the given constraints (minimization of drying time, unit energy consumption, color difference, and maximization of rehydration ratio, polysaccharide content, and allantoin content), BP-GWO was found to have higher coefficients of determination (R2 = 0.9919 to 0.9983) and lower RMSEs (reduced by 61.34% to 80.03%) than RMS. Multi-objective optimization of BP-GWO was carried out to obtain the optimal drying conditions, as follows: temperature 63.57 °C, slice thickness 4.27 mm, radiation distance 91.39 mm, corresponding to the optimal indices, as follows: Y1 = 133.71 min, Y2 = 7.26, Y3 = 8.54 kJ·h·kg−1, Y4 = 20.73 mg/g, Y5 = 2.84 kg/kg, and Y6 = 3.69 μg/g. In the experimental verification of the prediction results, the relative error between the actual and predicted values was less than 5%, proving the model’s reliability for other materials in the drying technology process research to provide a reference.

To control seasonal influenza epidemics in elders, a quadrivalent, inactivated, split-virion influenza vaccine (IIV4) comprising A and B lineages is produced for young individuals and adults aged ≥60 years. In this phase III, randomized, double-blind, active-controlled trial, we compared safety and immunogenicity of IIV4 with a licensed quadrivalent inactivated vaccine (IIV4-HL) produced by Hualan Biological Engineering during the 2019 influenza season. Participants were randomly assigned to receive IIV4 (n = 959) or IIV4-HL (n = 959). Compared to IIV4-HL, geometric mean titers (GMT) of hemagglutination inhibition (HAI) titers and seroconversion rate (SCR) of IIV4 demonstrated better antibody responses in A lineages (H1N1 and H3N2) (P .01) in both age groups. After immunization, IIV4 provided a satisfactory SCR and seroprotection rate (SPR) in elders. No discernible variation in immunogenicity was observed between the two age cohorts. In both age groups, IIV4 and IIV4-HL recipients experienced similar levels of solicited and unsolicited adverse events (AEs), and the incidence of AEs was low in both vaccine groups. Most AEs were of mild-to-moderate severity and no grade 3 AEs in IIV4 group, but AEs in adults aged 60–65 were little higher than in adults over 65 years in IIV4 and IIV4-HL groups (IIV4: 14.66% vs. 10.36%; IIV4-HL:14.67% vs. 11.43%). Totally, IIV4 was generally well tolerated and induced high antibody titers against all four influenza strains in elderly, making it a compelling alternative for the elderly aged ≥60 years. Trial registration: Clinical Trials.gov: 2015L00649-2.

Surface acoustic wave (SAW) can be used as passive wireless sensors in high temperature environments. For such applications, protective layers are crucial and important for the SAW sensors. In this paper, ultra-thin Al2O3 layers prepared by atomic layer deposition (ALD) and RF magnetron sputtering were used to protect SAW devices with platinum (Pt) electrodes and their temperature stability was studied systematically. The devices were thermally treated up to 1150 °C in air, the real-time resistance of Pt resistive tracks with a sputtering Al2O3 protective layer showed much better and improved thermal stability than those without or with an ALD Al2O3 protective layer. Microstructure characterizations showed that the superior temperature stability is attributed to its mixture of amorphous and nano-crystalline nature of the Al2O3 layer deposited by sputtering and full recrystallization at high temperatures. SAW devices with a sputtering Al2O3 protective layer after 1150 °C treatment maintained almost unchanged properties, while those with an ALD Al2O3 protective layer failed to work. Investigation also indicated there exists an optimal thickness for the sputtering Al2O3 layer to achieve best performance and thermal-stability for the SAW devices. Besides, the deposition rate of Al2O3 layer by sputtering is 10 times faster than that by ALD. All the results demonstrate that the sputtering Al2O3 protective layer is more suitable for high temperature SAW device applications owing to its lower cost, higher deposition rate and temperature stability.

Using hot air drying (HAD) and combined infrared hot air drying (IR-HAD) test devices, the drying kinetics, unit energy consumption, color difference values, rehydration rate, microstructure, and changes in polysaccharide and allantoin contents of yam slices were examined at various temperatures (50 °C, 55 °C, 60 °C, 65 °C, and 70 °C). The findings demonstrated that each of the aforementioned parameters was significantly impacted by the drying temperature. IR-HAD dries quicker and takes less time to dry than HAD. The Deff of IR-HAD is higher than that of HAD at the same temperature and increases with the increase in temperature. The activation energy required for IR-HAD (26.35 kJ/mol) is lower than that required for HAD (32.53 kJ/mol). HAD uses more energy per unit than IR-HAD by a factor of greater than 1.3. Yam slices treated with IR-HAD had higher microscopic porosity, better rehydration, lower color difference values, and higher polysaccharide and allantoin levels than HAD-treated yam slices. The IR-HAD at 60 °C had the greatest comprehensive rating after a thorough analysis of the dried yam slices using the coefficient of variation method. Three statistical indicators were used to evaluate six thin-layer drying models, and the Weibull model was most applicable to describe the variation of drying characteristics of yam slices.

A drying temperature precision control system was studied to provide technical support for developing and further proving the superiority of the variable-temperature drying process. In this study, an improved neural network (INN) proportional–integral–derivative (PID) controller (INN-PID) was designed. The dynamic performance of the PID, neural network PID (NN-PID) and INN-PID controllers was simulated with unit step signals as an input in MATLAB software. A drying temperature precision control system was set up in an air impingement dryer, and the drying temperature control experiment was carried out to verify the performance of the three controllers. Linear variable-temperature (LVT) and constant-temperature drying experiments of cantaloupe slices were carried out based on the system. Moreover, the experimental results were evaluated comprehensively with the brightness (L value), colour difference (ΔE), vitamin C content, chewiness, drying time and energy consumption (EC) as evaluation indexes. The simulation results show that the INN-PID controller outperforms the other two controllers in terms of control accuracy and regulation time. In the drying temperature control experiment at 50 °C–55 °C, the peak time of the INN-PID controller is 237.37 s, the regulation time is 134.91 s and the maximum overshoot is 4.74%. The INN-PID controller can quickly and effectively regulate the temperature of the inner chamber of the air impingement dryer. Compared with constant-temperature drying, LVT is a more effective drying mode as it ensures the quality of the material and reduces the drying time and EC. The drying temperature precision control system based on the INN-PID controller meets the temperature control requirements of the variable-temperature drying process. This system provides practical and effective technical support for the variable-temperature drying process and lays the foundation for further research. The LVT drying experiments of cantaloupe slices also show that variable-temperature drying is a better process than constant-temperature drying and is worthy of further study to be applied in production.

This study combined an artificial neural network (ANN) with a genetic algorithm (GA) to obtain the model and optimal process parameters of drying-assisted walnut breaking. Walnuts were dried at different IR temperatures (40 °C, 45 °C, 50 °C, and 55 °C) and air velocities (1, 2, 3, and 4 m/s) to different moisture contents (10%, 15%, 20%, and 25%) by using air-impingement technology. Subsequently, the dried walnuts were broken in different loading directions (sutural, longitudinal, and vertical). The drying time (DT), specific energy consumption (SEC), high kernel rate (HR), whole kernel rate (WR), and shell-breaking rate (SR) were determined as response variables. An ANN optimized by a GA was applied to simulate the influence of IR temperature, air velocity, moisture content, and loading direction on the five response variables, from which the objective functions of DT, SEC, HR, WR, and SR were developed. A GA was applied for the simultaneous maximization of HR, WR, and SR and minimization of DT and SEC to determine the optimized process parameters. The ANN model had a satisfactory prediction ability, with the coefficients of determination of 0.996, 0.998, 0.990, 0.991, and 0.993 for DT, SEC, HR, WR, and SR, respectively. The optimized process parameters were found to be 54.9 °C of IR temperature, 3.66 m/s of air velocity, 10.9% of moisture content, and vertical loading direction. The model combining an ANN and a GA was proven to be an effective method for predicting and optimizing the process parameters of walnut breaking. The predicted values under optimized process parameters fitted the experimental data well, with a low relative error value of 2.51–3.96%. This study can help improve the quality of walnut breaking, processing efficiency, and energy conservation. The ANN modeling and GA multiobjective optimization method developed in this study provide references for the process optimization of walnut and other similar commodities.

Safe and effective vaccines are still urgently needed to cope with the ongoing COVID-19 pandemic. Recently, we developed a recombinant COVID-19 vaccine (V-01) containing fusion protein (IFN-PADRE-RBD-Fc dimer) as antigen verified to induce protective immunity against SARS-CoV-2 challenge in pre-clinical study, which supported progression to Phase I clinical trials in humans. A Randomized, double-blind, placebo-controlled Phase I clinical trial was initiated at the Guangdong Provincial Center for Disease Control and Prevention (Gaozhou, China) in February 2021. Healthy adults aged between 18 and 59 years and over 60 years were sequentially enrolled and randomly allocated into three subgroups (1:1:1) either to receive the vaccine (10, 25, and 50 μg) or placebo (V-01: Placebo = 4:1) intramuscularly with a 21-day interval by a sentinel and dose escalation design. The data showed a promising safety profile with approximately 25% vaccine-related overall adverse events (AEs) within 30 days and no grade 3 or worse AEs. Besides, V-01 provoked rapid and strong immune responses, elicited substantially high-titre neutralizing antibodies and anti-RBD IgG peaked at day 35 or 49 after first dose, presented with encouraging immunogenicity at low dose (10 μg) subgroup and elderly participants, which showed great promise to be used as all-aged (18 and above) vaccine against COVID-19. Taken together, our preliminary findings indicate that V-01 is safe and well tolerated, capable of inducing rapid and strong immune responses, and warrants further testing in Phase II/III clinical trials.

Abstract Low-voltage-triggered silicon-controlled rectifier (LVTSCR) is expected to provide an electrostatic discharge (ESD) protection for a low-voltage integrated circuit. However, it is normally vulnerable to the latch-up effect due to its extremely low holding voltage. In this paper, a novel LVTSCR embedded with an extra p-type MOSFET called EP-LVTSCR has been proposed and verified in a 28-nm CMOS technology. The proposed device possesses a lower trigger voltage of ~ 6.2 V and a significantly higher holding voltage of ~ 5.5 V with only 23% degradation of the failure current under the transmission line pulse test. It is also shown that the EP-LVTSCR operates with a lower turn-on resistance of ~ 1.8 Ω as well as a reliable leakage current of ~ 1.8 nA measured at 3.63 V, making it suitable for ESD protections in 2.5 V/3.3 V CMOS processes. Moreover, the triggering mechanism and conduction characteristics of the proposed device were explored and demonstrated with TCAD simulation.

We identified SARS-CoV-2 specific antigen epitopes by HLA-A2 binding affinity analysis and characterized their ability to activate T cells. As the pandemic continues, variations in SARS-CoV-2 virus strains have been found in many countries. In this study, we directly assess the immune response to SARS-CoV-2 epitope variants. We first predicted potential HLA-A*02:01-restricted CD8+ T-cell epitopes of SARS-CoV-2. Using the T2 cell model, HLA-A*02:01-restricted T-cell epitopes were screened for their binding affinity and ability to activate T cells. Subsequently, we examined the identified epitope variations and analyzed their impact on immune response. Here, we identified specific HLA-A2-restricted T-cell epitopes in the spike protein of SARS-CoV-2. Seven epitope peptides were confirmed to bind with HLA-A*02:01 and potentially be presented by antigen-presenting cells to induce host immune responses. Tetramers containing these peptides could interact with specific CD8+ T cells from convalescent COVID-19 patients, and one dominant epitope (n-Sp1) was defined. These epitopes could activate and generate epitope-specific T cells in vitro, and those activated T cells showed cytolytic activity toward target cells. Meanwhile, n-Sp1 epitope variant 5L>F significantly decreased the proportion of specific T-cell activation; n-Sp1 epitope 8L>V variant showed significantly reduced binding to HLA-A*02:01 and decreased proportion of n-Sp1-specific CD8+ T cell, which potentially contributes to the immune escape of SARS-CoV-2. Our data indicate that the variation of a dominant epitope will cause the deficiency of HLA-A*02:01 binding and T-cell activation, which subsequently requires the formation of a new CD8+ T-cell immune response in COVID-19 patients.

A highly sensitive and precise Love wave mode surface acoustic wave (SAW) immunosensor based on an ST-cut 90°X quartz substrate and an SiO2 wave-guiding layer was developed to detect cancer-related biomarkers of carcinoembryonic antigens (CEAs). A delay line structure of the SAW device with a resonant frequency of 196 MHz was designed/fabricated, and its surface was functionalized through CEA antibody immobilization. The CEA antibodies were bound with gold nanoparticles and CEA antibodies to form a sandwich structure, which significantly amplified the mass loading effect and enhanced the maximum responses by 30 times. The center frequency of the Love wave immunosensor showed a linear response as a function of the CEA concentration in the range of 0.2–5 ng/mL. It showed a limit of detection of 0.2 ng/mL, and its coefficient of determination was 0.983. The sensor also showed minimal interference from nonspecific adsorptions, thus demonstrating its promise for point-of-care applications for cancer biomarkers.

This paper proposes a displacement sensing method based on magnetic flux measurement. A bridge-structured magnetic circuit, formed by permanent magnets and two ferromagnetic cores, is designed and discussed. The analyses of the equivalent magnetic circuit and three-dimensional finite element simulations showed that the magnetic flux density changes linearly with the reciprocal of the sum of a constant and the displacement. A prototype sensor of the bridge structure is developed that consists of four permanent magnets as excitation, a Hall sensor as reception, and two ferromagnetic cores as the connection. Experiments have validated the feasibility of this method. The measured results show a good linearity between the sensor’s output and the reciprocal of the sum of a constant and the displacement, with a correlation coefficient greater than 0.9995 across different measurement ranges. Additionally, the measured results significantly indicate that the proposed sensor is compatible with different ferromagnetic materials with a worst-case error of less than 5%. The proposed sensor has the advantages of low cost and good linearity; however, the test object is limited to ferromagnetic materials.

Insights into the potential candidate hub genes may facilitate the generation of safe and effective immunity against seasonal influenza as well as the development of personalized influenza vaccines for the elderly at high risk of influenza virus infection. This study aimed to identify the potential hub genes related to the immune induction process of the 2018/19 seasonal quadrivalent inactivated influenza vaccines (QIVs) in the elderly ≥60 years by using weighted gene co-expression network analysis (WGCNA). From 63 whole blood samples from16 elderly individuals, a total of 13,345 genes were obtained and divided into eight co-expression modules, with two modules being significantly correlated with vaccine-induced immune responses. After functional enrichment analysis, genes under GO terms of vaccine-associated immunity were used to construct the sub-network for identification and functional validation of hub genes. MCEMP1 and SPARC were confirmed as the hub genes with an obvious effect on QIVs-induced immunity. The MCEMP1 expression was shown to be negatively correlated with the QIVs-associated reactogenicity within 7 days after vaccination, which could be suppressed by the CXCL 8/IL-8 and exacerbated by the Granzyme-B cytotoxic mediator. Meanwhile, the SPARC expression was found to increase the immune responses to the QIVs and contribute to the persistence of protective humoral antibody titers. These two genes can be used to predict QIVs-induced adverse reaction, the intensity of immune responses, and the persistence of humoral antibody against influenza. This work has shed light on further research on the development of personalized QIVs with appropriate immune responses and long-lasting immunity against the forthcoming seasonal influenza.

Feline calicivirus (FCV) belongs to the Caliciviridae, which comprises small RNA viruses of both medical and veterinary importance. Once infection has occurred, FCV can persist in the cat population, but the molecular mechanism of how it escapes the innate immune response is still unknown. In this study, we found FCV strain 2280 to be relatively resistant to treatment with IFN-β. FCV 2280 infection inhibited IFN-induced activation of the ISRE (Interferon-stimulated response element) promoter and transcription of ISGs (Interferon-stimulated genes). The mechanistic analysis showed that the expression of IFNAR1, but not IFNAR2, was markedly reduced in FCV 2280-infected cells by inducing the degradation of IFNAR1 mRNA, which inhibited the phosphorylation of downstream adaptors. Further, overexpression of the FCV 2280 nonstructural protein p30, but not p30 of the attenuated strain F9, downregulated the expression of IFNAR1 mRNA. His-p30 fusion proteins were produced in Escherichia coli and purified, and an in vitro digestion assay was performed. The results showed that 2280 His-p30 could directly degrade IFNAR1 RNA but not IFNAR2 RNA. Moreover, the 5'UTR of IFNAR1 mRNA renders it directly susceptible to cleavage by 2280 p30. Next, we constructed two chimeric viruses: rFCV 2280-F9 p30 and rFCV F9-2280 p30. Compared to infection with the parental virus, rFCV 2280-F9 p30 infection displayed attenuated activities in reducing the level of IFNAR1 and inhibiting the phosphorylation of STAT1 and STAT2, whereas rFCV F9-2280 p30 displayed enhanced activities. Animal experiments showed that the virulence of rFCV 2280-F9 p30 infection was attenuated but that the virulence of rFCV F9-2280 p30 was increased compared to that of the parental viruses. Collectively, these data show that FCV 2280 p30 could directly and selectively degrade IFNAR1 mRNA, thus blocking the type I interferon-induced activation of the JAK-STAT signalling pathway, which may contribute to the pathogenesis of FCV infection.

This study aimed to evaluate enterovirus 71 (EV-A71) vaccine candidate strains, including their genotypes, immunogenicity and cross-neutralization capacity. From clinical samples, EV-A71 strains were separated by using Vero cells. Six strains were chosen for vaccine candidates, and the sequences were analyzed. To detect the immunogenicity of the strains, we used them to immunize NIH mice at 0 and 14 days. Cytopathic effects (CPE) were examined to determine the EV-A71 neutralizing antibody (NTAb) titer 14 d after the first and second inoculations. To evaluate the cross-neutralizing capacity of the EV-A71 vaccine candidate strains, we tested serum immunized mice with ten EV-A71 genotype strains. Six EV-A71 vaccine candidate strains were identified, all belonging to sub-genotype C4, the prevalent genotype in China. The sequence similarity of the VP1 regions of the six candidate vaccine strains and three approved inactivated vaccines was 97.58%–97.77%, and the VP1 amino acid similarity was 98.65%–99.33%. Experiments were performed to evaluate the immunogenicity and cross-neutralizing activity of the EV-A71 vaccine candidate strains. The strains had good immunogenicity 14 d after two immunizations, inducing an NTAb titer ranging from 1:94 to 1:346. The NTAb seroconversion rates 14 d after one immunization were above 80% (except HB0007), and significantly increased immunogenicity of EV-A71 strains was observed post-inoculation. Furthermore, our candidate vaccine strains had broad cross-neutralizing activity after challenge with ten sub-genotypes of EV-A71. The highest NTAb titer/lowest NTAb titer ratios of sera against EV-A71 sub-genotypes were 8.0 (JS0002), 8.0 (JS0005), 21.3 (HB0005), 21.3 (HB0007), 10.7 (HB0040) and 8.0 (GD0002), respectively. Our EV-A71 strains had good immunogenicity and cross-neutralization activity, and have the potential to serve as vaccine strains for multivalent hand, foot and mouth disease vaccines.

The melt content is significant characteristic for the low velocity layer, so it is very necessary to set up the quantitative relationship between the low velocity anomaly and the melt fraction. We describe the computational methods for melt volume fractions and discussed the parameter selections for the theoretical computations. • We discuss the seismic wave velocity characteristics and the equilibrium geometry model in the partial melting system. • Equations for computing the elastic properties atop the LVL are presented. • Parameter selection of the equilibrium geometry model is shown.

Bluetongue virus (BTV) is an important pathogen of wild and domestic ruminants. Despite extensive study in recent decades, the interplay between BTV and host cells is not clearly understood. Autophagy as a cellular adaptive response plays a part in many viral infections. In our study, we found that BTV1 infection triggers the complete autophagic process in host cells, as demonstrated by the appearance of obvious double-membrane autophagosome-like vesicles, GFP-LC3 dots accumulation, the conversion of LC3-I to LC3-II and increased levels of autophagic flux in BSR cells (baby hamster kidney cell clones) and primary lamb lingual epithelial cells upon BTV1 infection. Moreover, the results of a UV-inactivated BTV1 infection assay suggested that the induction of autophagy was dependent on BTV1 replication. Therefore, we investigated the role of autophagy in BTV1 replication. The inhibition of autophagy by pharmacological inhibitors (3-MA, CQ) and RNA interference (siBeclin1) significantly decreased viral protein synthesis and virus yields. In contrast, treating BSR cells with rapamycin, an inducer of autophagy, promoted viral protein expression and the production of infectious BTV1. These findings lead us to conclude that autophagy is activated by BTV1 and contributes to its replication, and provide novel insights into BTV-host interactions.

Feline infectious peritonitis (FIP), caused by virulent feline coronavirus, is the leading infectious cause of death in cats. The type I interferon (type I IFN)-mediated immune responses provide host protection from infectious diseases. Several coronaviruses have been reported to evolve diverse strategies to evade host IFN response. However, whether feline infectious peritonitis virus (FIPV) antagonizes the type I IFN signaling remains unclear. In this study, we demonstrated that FIPV strain DF2 infection not only failed to induce interferon-β (IFN-β) and interferon-stimulated gene (ISG) production, but also inhibited Sendai virus (SEV) or polyinosinic-polycytidylic acid (poly(I:C))-induced IFN-β production. Subsequently, we found that one of the non-structural proteins encoded by the FIPV genome, nsp5, interrupted type I IFN signaling in a protease-dependent manner by cleaving the nuclear factor κB (NF-κB) essential modulator (NEMO) at three sites—glutamine132 (Q132), Q205, and Q231. Further investigation revealed that the cleavage products of NEMO lost the ability to activate the IFN-β promoter. Mechanistically, the nsp5-mediated NEMO cleavage disrupted the recruitment of the TRAF family member-associated NF-κB activator (TANK) to NEMO, which reduced the phosphorylation of interferon regulatory factor 3 (IRF3), leading to the inhibition of type I IFN production. Our research provides new insights into the mechanism for FIPV to counteract host innate immune response.

Classically, all hepatitis E virus (HEV) variants causing human infection belong to the genus Paslahepevirus (HEV-A). However, the increasing cases of rat HEV infection in humans since 2018 challenged this dogma, posing increasing health threats. Herein, we investigated the underlying mechanisms dictating the zoonotic potentials of different HEV species and their possible cross-protection relationships. We found that rat HEV virus-like particles (HEVVLPs) bound to human liver and intestinal cells/tissues with high efficiency. Moreover, rat HEVVLPs and infectious rat HEV particles penetrated the cell membrane and entered human target cells postbinding. In contrast, ferret HEVVLPs showed marginal cell binding and entry ability, bat HEVVLPs and avian HEVVLPs exhibited no binding and entry potency. Structure-based three-dimensional mapping identified that the surface spike domain of rat HEV is crucial for cell binding. Antigenic cartography indicated that rat HEV exhibited partial cross-reaction with HEV-A. Intriguingly, sera of HEV-A infected patients or human HEV vaccine Hecolin® immunized individuals provided partial cross-protection against the binding of rat HEVVLPs to human target cells. In summary, the interactions between the viral capsid and cellular receptor(s) regulate the distinct zoonotic potentials of different HEV species. The systematic characterization of antigenic cartography and serological cross-reactivity of different HEV species provide valuable insights for the development of species-specific diagnosis and protective vaccines against zoonotic HEV infection. [ABSTRACT FROM AUTHOR]

Formation of bacterial films on structural surfaces often leads to severe contamination of medical devices, hospital equipment, implant materials, etc., and antimicrobial resistance of microorganisms has indeed become a global health issue. Therefore, effective therapies for controlling infectious and pathogenic bacteria are urgently needed. Being a promising active method for this purpose, surface acoustic waves (SAWs) have merits such as nanoscale earthquake-like vibration/agitation/radiation, acoustic streaming induced circulations, and localised acoustic heating effect in liquids. However, only a few studies have explored controlling bacterial growth and inactivation behaviour using SAWs. In this study, we proposed utilising piezoelectric thin film-based SAW devices on a silicon substrate for controlling bacterial growth and inactivation with and without using ZnO micro/nanostructures. Effects of SAW powers on bacterial growth for two types of bacteria, i.e., E. coli and S. aureus, were evaluated. Varied concentrations of ZnO tetrapods were also added into the bacterial culture to study their effects and the combined antimicrobial effects along with SAW agitation. Our results showed that when the SAW power was below a threshold (e.g., about 2.55 W in this study), the bacterial growth was apparently enhanced, whereas the further increase of SAW power to a high power caused inactivation of bacteria. Combination of thin film SAWs with ZnO tetrapods led to significantly decreased growth or inactivation for both E. coli and S. aureus, revealing their effectiveness for antimicrobial treatment. Mechanisms and effects of SAW interactions with bacterial solutions and ZnO tetrapods have been systematically discussed. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) infection can cause severe complications and high mortality, particularly in pregnant women, organ transplant recipients, individuals with pre-existing liver disease and immunosuppressed patients. However, there are still unmet needs for treating chronic HEV infections. Herein, we screened a best-in-class drug repurposing library consisting of 262 drugs/compounds. Upon screening, we identified vidofludimus calcium and pyrazofurin as novel anti-HEV entities. Vidofludimus calcium is the next-generation dihydroorotate dehydrogenase (DHODH) inhibitor in the phase 3 pipeline to treat autoimmune diseases or SARS-CoV-2 infection. Pyrazofurin selectively targets uridine monophosphate synthetase (UMPS). Their anti-HEV effects were further investigated in a range of cell culture models and human liver organoids models with wild type HEV strains and ribavirin treatment failure-associated HEV strains. Encouragingly, both drugs exhibited a sizeable therapeutic window against HEV. For instance, the IC50 value of vidofludimus calcium is 4.6-7.6-fold lower than the current therapeutic doses in patients. Mechanistically, their anti-HEV mode of action depends on the blockage of pyrimidine synthesis. Notably, two drugs robustly inhibited ribavirin treatment failure-associated HEV mutants (Y1320H, G1634R). Their combination with IFN-a resulted in synergistic antiviral activity. In conclusion, we identified vidofludimus calcium and pyrazofurin as potent candidates for the treatment of HEV infections. Based on their antiviral potency, and also the favorable safety profile identified in clinical studies, our study supports the initiation of clinical studies to repurpose these drugs for treating chronic hepatitis E. [ABSTRACT FROM AUTHOR]