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Rock deformation modulus is one of the key parameters for the design and construction of underground rock engineering. Obtaining accurate rock deformation modulus is crucial for a comprehensive analysis of the deformation behavior of the surrounding rock in deep rock engineering. To achieve this goal, the commonly used methods for calculating rock deformation modulus are systematically sorted out and summarized. Furthermore, the rock deformation modulus is inverse-calculated by simulating in-situ tests using the finite element method, and the results are verified and analyzed by comparing them with the in-situ test results. For the actual project of deep shaft, a numerical calculation model is established to conduct an inversion analysis of rock deformation modulus of different lithologies in the deep strata. Additionally, a sensitivity analysis is performed on different strength criteria, Poisson's ratio and rock cohesion on rock deformation modulus. Finally, the numerical simulation inversion results are compared and discussed with the empirical formula calculation results. The results show that the values of rock deformation modulus obtained from numerical inversion using finite element method are in good agreement with those calculated based on the experimental rigid plate load test; While Poisson's ratio does have some influence on rock deformation modulus, the sensitivity of rock deformation modulus to Poisson's ratio is generally low; When the cohesion of the rock mass is small, the choice of strength criterion has a significant influence on the inversion results of deformation modulus, and vice versa; the sensitivity of the rock deformation modulus to the changes of the rock cohesion varies depending on the depth and lithology of the strata; the deformation modulus of the rock mass obtained by numerical inversion has a good correlation with some empirical equations. Therefore, the numerical simulation and empirical formulae are useful during planning, design and development of deep rock projects to perform the inversion calculation of rock deformation modulus, thereby ensuring greater safety and economy.

Abstract Background Nonalcoholic fatty liver disease (NAFLD) is a chronic disease with an increasing incidence, which can further develop into liver fibrosis and hepatocellular carcinoma at the end stage. Alantolactone (Ala), a sesquiterpene lactone isolated from Asteraceae, has shown anti-inflammatory effects in different models. However, the therapeutic effect of Ala on NAFLD is not clear. Methods C57BL/6 mice were fed a high-fat diet (HFD) to induce NAFLD. After 16 weeks, Ala was administered by gavage to observe its effect on NAFLD. RNA sequencing of liver tissues was performed to investigate the mechanism. In vitro, mouse cell line AML-12 was pretreated with Ala to resist palmitic acid (PA)-induced inflammation, oxidative stress and fibrosis. Results Ala significantly inhibited inflammation, fibrosis and oxidative stress in HFD-induced mice, as well as PA-induced AML-12 cells. Mechanistic studies showed that the effect of Ala was related to the induction of Nrf2 and the inhibition of NF-κB. Taken together, these findings suggested that Ala exerted a liver protective effect on NAFLD by blocking inflammation and oxidative stress. Conclusions The study found that Ala exerted a liver protective effect on NAFLD by blocking inflammation and oxidative stress, suggesting that Ala is an effective therapy for NAFLD.

This paper assessed the electromigration behavior of ethanolamine and its efficiency as a corrosion inhibitor of rebar during the realkalization. Cylindrical concrete specimen (diameter 45 mm, height 20 mm) with steel rebar (6 mm in diameter, 35 mm in length) were artificially carbonated and corroded in an accelerated manner with impressed anodic current. The specimens were realkalized in the electrolyte solution containing ethanolamine, while the steel rebars were connected to the cathodic current (200 mA·h, 1 A/m2). After 25 days of monitoring the repair process, experimental data revealed notable changes in electrochemical parameters. The corrosion potential increased from −627 mV to −236 mV, signifying a reduction in corrosion activity. The cathodic exchange current density decreased from 4.9 μA/cm2 to 2.3 μA/cm2, showing a decrease in the corrosion rate. Also, the pH value of the solution dropped to a comparatively lower level, the ethanolamine and potassium ion concentrations decreased from 22 to 30.54 g/L to 3.22 and 10.23 g/L, respectively. Moreover, nitrogen detection on the steel surface and varied levels of ethanolamine concentration at different depths in the concrete were also measured, both indicating a clear migration of inhibitor to the steel surface to form a passive film.

Abstract Background Severe bacterial infections can trigger acute lung injury (ALI) and acute respiratory distress syndrome, with bacterial pathogen‐associated molecular patterns (PAMPs) exacerbating the inflammatory response, particularly in COVID‐19 patients. Cyclic‐di‐GMP (CDG), one of the PAMPs, is synthesized by various Gram‐positve and Gram‐negative bacteria. Previous studies mainly focused on the inflammatory responses triggered by intracellular bacteria‐released CDG. However, how extracellular CDG, which is released by bacterial autolysis or rupture, activates the inflammatory response remains unclear. Methods The interaction between extracellular CDG and myeloid differentiation protein 2 (MD2) was investigated using in vivo and in vitro models. MD2 blockade was achieved using specific inhibitor and genetic knockout mice. Site‐directed mutagenesis, co‐immunoprecipitation, SPR and Bis‐ANS displacement assays were used to identify the potential binding sites of MD2 on CDG. Results Our data show that extracellular CDG directly interacts with MD2, leading to activation of the TLR4 signalling pathway and lung injury. Specific inhibitors or genetic knockout of MD2 in mice significantly alleviated CDG‐induced lung injury. Moreover, isoleucine residues at positions 80 and 94, along with phenylalanine at position 121, are essential for the binding of MD2 to CDG. Conclusion These results reveal that extracellular CDG induces lung injury through direct interaction with MD2 and activation of the TLR4 signalling pathway, providing valuable insights into bacteria‐induced ALI mechanisms and new therapeutic approaches for the treatment of bacterial co‐infection in COVID‐19 patients.

The issue of significant floor heave deformation in gob-side entry retaining has long been a challenging problem in the context of longwall mining. This paper studies the floor heave failure mechanism and control method for gob-side entry retaining with concrete blocks in Guizhou Faer Coal Mine in China. Based on Rankine’s earth pressure theory, the effective shear stress equation for the plastic slip of roadway floor is established. The deformation mechanism of floor heave in a retaining roadway with a block wall is revealed in this study. The new comprehensive control method is proposed, encompassing roof pre-splitting blasting for pressure relief, reinforcing cables for roof control, double directions control bolts for concrete block, and pliability cushion yielding pressure. FLAC3D numerical calculation model is established, which shows that the new method can effectively reduce the average vertical stress peak value of the entity coal floor by 34.6% and significantly reduce the pressure source causing the roadway floor heave. Besides, a multi-parameter real-time online monitoring system for mine pressure was designed, and field tests were carried out. The results show that the maximum value of roadway floor heave under the new method is 163 mm, reduced by 66.9%, and the roadway floor heave is effectively controlled. These research findings offer a fresh perspective and new ideas for controlling floor heave in mining operations.

Abstract Deprived urban areas, commonly referred to as ‘slums,’ are the consequence of unprecedented urbanisation. Previous studies have highlighted the potential of Artificial Intelligence (AI) and Earth Observation (EO) in capturing physical aspects of urban deprivation. However, little research has explored AI’s ability to predict how locals perceive deprivation. This research aims to develop a method to predict citizens’ perception of deprivation using satellite imagery, citizen science, and AI. A deprivation perception score was computed from slum-citizens’ votes. Then, AI was used to model this score, and results indicate that it can effectively predict perception, with deep learning outperforming conventional machine learning. By leveraging AI and EO, policymakers can comprehend the underlying patterns of urban deprivation, enabling targeted interventions based on citizens’ needs. As over a quarter of the global urban population resides in slums, this tool can help prioritise citizens’ requirements, providing evidence for implementing urban upgrading policies aligned with SDG-11.

Single Recovery Roadway (SRR) is a novel retraction technology in the non-pillars mining innovation system. In previous support withdrawing, single recovery roadway was usually replaced by a dual-recovery roadway or cut the coal wall before the support. This study is set against the background of the longwall panel at Duanshi Coal Mine, where a mechanical model based on the stress characteristics of a composite cantilever beam was constructed to analyze the failure of the main roof in a single recovery roadway. Through numerical analysis, the relationship between deformation failure of the recovery roadway and interlayer slippage structures was explored, as well as how mining-induced stress distribution and the evolution of key strata fractures impact the stability of the roadway. The results indicate that after the connection of the longwall panel and the recovery roadway, the overlying composite interlayered rock strata are affected by the interlayer slippage structures, leading to significant asymmetric deformation in the surrounding rocks. Additionally, borehole observation data support the theoretical calculations of the cantilever beam model. These research results enhance the understanding of the interlayer slip instability mechanism and provide important guidance for mine design under similar geological conditions.

Abstract The volume evolution behavior of rock fissures and the characteristics of acoustic emission under cyclic loading are critical for rock stability analysis. To study the volume change behavior of monzogranite fissures and the characteristics of acoustic emission signals under cyclic loading, we selected samples of monzogranite at − 1600 m from a gold mine located in the Jiaodong Peninsula at a depth of − 1600 m and investigated the samples using triaxial cyclic loading—unloading tests and acoustic emission monitoring. As the volume change behavior of the monzogranite fissures and acoustic emission signals were monitored and recorded, the calculated fracture volume strain ratio coefficient and acoustic emission entropy value were proposed to describe the evolution process of fissures inside the rock. The research results showed that the volume strain ratio curve of the rock fractures exhibited a logarithmic variation characteristic during the cyclic loading and unloading, and the fracture volume strain ratio better reflected the relative scale of the internal fracture strain in the rock to the total volume strain. The acoustic emission entropy value reflected the crack evolution behavior during the loading and failure processes, which was a rapid decline in the initial stage of loading and a rapid upward trend in the failure stage. The observed “V”-shaped change in the acoustic emission entropy can be used as an early warning for rock failure. The research results can provide theoretical guidance for rock stability analysis.

Increasing tenure security is essential for promoting safe and inclusive urban development and achieving Sustainable Development Goals. However, assessment of tenure security relies on conventional census and survey statistics, which often fail to capture the dimension of perceived tenure insecurity. This perceived tenure insecurity is crucial as it influences local engagement and the effectiveness of policies. In many regions, particularly in the Global South, these conventional methods lack the necessary data to adequately measure perceived tenure insecurity. This study first used household survey data to derive variations in perceived tenure insecurity and then explored the potential of Very-High Resolution (VHR) satellite imagery and spatial data to assess these variations in urban deprived areas. Focusing on the city of Kigali, Rwanda, the study collected household survey data, which were analysed using Multiple Correspondence Analysis to capture variations of perceived tenure insecurity. In addition, VHR satellite imagery and spatial datasets were analysed to characterize urban deprivation. Finally, a Random Forest regression model was used to assess the relationship between variations of perceived tenure insecurity and the spatial characteristics of urban deprived areas. The findings highlight the potential of geospatial information to estimate variations in perceived tenure insecurity within urban deprived contexts. These insights can inform evidence-based decision-making by municipalities and stakeholders in urban development initiatives.

Hypervirulent carbapenem-resistant Acinetobacter baumannii (hv-CRAB) has emerged in bloodstream infections (BSI). Cases of BSI caused by hv-CRAB (hv-CRAB-BSI) had posed a significant threat to hospitalized patients. In this study, 31 CRAB strains isolated from Chinese BSI patients were analyzed, of which 24 were identified as hv-CRAB-BSI and 7 as non-hv-CRAB-BSI, using the Galleria mellonella infection model. Patients with hv-CRAB-BSI had higher rates of septic shock (79.2% vs. 14.3%, p = 0.004) and mortality (66.7% vs. 14.3%, p = 0.028). All strains were resistant to most antibiotics but sensitive to colistin. Hv-CRAB-BSI showed lower resistance to minocycline than non-hv-CRAB-BSI (54.2% vs. 100%, p = 0.03). Whole-genome sequencing revealed that the detection rates of immune modulation genes ptk and epsA in hv-CRAB-BSI were significantly higher than in non-hv-CRAB-BSI (91.7% vs. 28.6%, p = 0.002). Additionally, all ST457 hv-CRAB-BSI lacked abaR, and all ST1486 non-hv-CRAB-BSI lacked adeG. The checkerboard dilution method assessed the efficacies of various antibiotic combinations, revealing that although synergism was rarely observed, the combination of colistin and minocycline showed the best efficacy for treating CRAB-BSI, regardless of whether the infections were hv-CRAB-BSI or non-hv-CRAB-BSI. These findings highlight the importance of analyzing molecular characteristics and exploring effective treatment strategies for hv-CRAB-BSI.

Operation strategy of the integrated wind-hydrogen system is the key to ameliorate the negative impacts of the fluctuated wind power on the hydrogen production capacity and durability of electrolyzer. However, the desalination system supplying pure water to electrolyzers was neglected previously, with which the practical operation strategy of the hybrid wind-hydrogen-desalination system has yet to be investigated. In this work, we proposed a novel control strategy named step-by-step start for wind-hydrogen-desalination system consisting of wind turbine, proton exchange membrane water electrolyzer (PEMWE), battery and batch reverse osmosis (BRO) desalination system, which can produce hydrogen and fresh water. Real-time wind data from Shenzhen, China were used as input to the integrated system. The results demonstrate the wind-hydrogen-desalination system with the proposed strategy can improve the hydrogen production by 17.55 %, the energy efficiency by 17.68 % in August, and increase hydrogen production by 10.29 %, the energy utilization efficiency by 10.44 % in December compared with traditional strategies. At low wind speeds, the switching times of PEMWE for this strategy is higher than the other strategies, while at high wind speeds, the switching times of PEMWE is significantly decreased. This work provides insights into the practical operation strategy for wind-hydrogen-desalination system depending on the real-time wind speed.

The concentration of antimicrobial agents in environments like water and food has increased rapidly, which led to a rapid increase in antimicrobial resistance levels in the environment. Monitoring of bacterial resistance levels is considered as a necessary means to control the bacterial resistance. Reference standards are critical for antimicrobial susceptibility testing. CLSI M45 A3 standard defines pathogenic microorganisms that cause infections less frequently than those covered by CLSI M02, M07, and M100 as Infrequently Isolated or Fastidious Bacteria and specifies antimicrobial susceptibility testing methods. Our study investigated the epidemiology and antimicrobial susceptibility testing data of Infrequently Isolated or Fastidious Bacteria strains isolated from blood specimens in 70 hospitals in Guangdong Province between 2017 and 2021. We defined testing methods other than those specified in CLSI M45 A3 as “Non-Standardized.” The proportion of standardized antimicrobial susceptibility testing for penicillin increased significantly (Corynebacterium spp. 17.4% vs. 50.0% p

β-AlFeSi is one of the most common and most damaging intermetallics in aluminum alloys containing silicon. The study of its growth behavior is crucial for alloy design. In this work, Al-8.1Si–5Fe and Al–13Si–3Fe alloys were cast to study the growth of β-AlFeSi. The skirt like β-AlFeSi clusters formed by splitting were discovered, and this phenomenon was found to be mainly caused by thermal stress. By micro to atomic scale electron microscopy studies, a layer-by-layer growth mode along the (001) crystal plane was proposed for β-AlFeSi. In addition, it is found that β-AlFeSi grows along the heat flow, and the preferred growth orientation is determined to be [100]/[010]. Other characteristics of β growth, such as stacking faults and inducing formation of pores, were also reported and discussed.

The durability of concrete is determined by its pore structure and permeability. The present work examines the effect of pore structure and porosity on the permeability of concrete after nearly a century natural carbonation. The samples were cored from a concrete building built in 1931. X-ray diffraction analysis, phenolphthalein dye test, Mercury Intrusion Porosimetry (MIP) were conducted to ascertain the composition, the carbonation depth, the permeability, the porosity and pore size distribution of samples. The experimental results revealed that the front of core samples was completely carbonated. The fractal dimension was calculated using the Mandelbrot model to characterize the pore structure. The combined harmless and less harmless pore proportions exhibited a linear correlation with the fractal dimension. A relationship between permeability and fractal dimension is established. The increase in the fractal dimension resulted in a gradual decrease in the oxygen diffusion coefficient. The diffusion coefficient tends to plateau when the fractal dimension exceeds a critical value of the combined pore proportion. While the pore proportion of concrete was higher than 14.64%, there was no significant effect on the permeability. The results of this study can serve for future assessments of concrete durability.

Abstract Objectives The present study aims to investigate the efficacy of utilizing three-dimensional (3D) printing technology in concert with Problem-Based Learning (PBL) and Case-Based Learning (CBL) pedagogical approaches in educating senior undergraduate clinical medical students on respiratory diseases. Methods A cohort of 422 fourth-year clinical medicical students of from Anhui Medical University, pursuing a five-year program, were arbitrarily segregated into two distinct groups. The experimental group was subjected to a combined pedagogical approach, which included 3D printing technology, PBL and CBL (referred to as DPC). Conversely, the control group was exposed to conventional teaching methodologies for respiratory disease education. The effectiveness of the teaching methods was subsequently appraised using both theoretical test scores and custom questionnaires. Results Post-quiz scores indicated a statistically significant improvement in the DPC group as compared to the traditional group (P 0.05). Conclusion The deployment of the DPC pedagogical approach may confer unique experiential learning opportunities for students, potentially enhancing theoretical test scores and promoting self-evaluation and satisfaction in the context of respiratory disease education. Hence, it may be instrumental in augmenting the overall teaching efficacy.

Abstract In longwall top coal caving (LTCC) mining methods, problems such as large deformations, loss of coal resources, and excavation relay out of balance are often encountered with the increased production in single mining panels. To address these problems, a novel non‐pillar coal mining technology in LTCC was used based on the equilibrium mining theory. This approach could cut off the stress transmission, eliminate the coal pillar, and retain the gob‐side entry. In this technology, the entry is first excavated along the roof of the coal, and then four techniques are applied to control the surrounding rock of the retained entry. The constant resistance and large deformation anchor cable are used to maintain the roof stability. The directional roof split blasting technique is adopted to separate the roof between the entry and gob. The blocking‐gangue support system (BGSS) is used to form the gangue rib lagging the mining panel. The temporary support system is applied to prevent the roadway from being affected by the dynamic pressure and prevented the BGSS from falling. Finally, the field monitoring results indicate that the surrounding rock of retained entry is stabilized at 200 m behind the working face. The deformation of retained entry is within a reasonable range at 180–190 m behind the mining panel. The results provide an important reference for the thick coal seam non‐pillar coal mining technology, specifically using this technology in LTCC panels.

Tidal flats are among the ecologically richest areas of the world where sediment composition (e.g. median grain size and silt content) and the macrozoobenthic presence play an important role in the health of the ecosystem. Regular monitoring of environmental and ecological variables is essential for sustainable management of the area. While monitoring based on field sampling is very time-consuming, the predictive performance of these variables using satellite images is low due to the spectral homogeneity over these regions. We tested a novel approach that uses features from a variational autoencoder (VAE) model to enhance the predictive performance of remote sensing images for environmental and ecological variables of tidal flats. The model was trained using the Sentinel-2 spectral bands to reproduce the input images, and during this process, the VAE model represents important information on the tidal flats within its layer structure. The information in the layers of the trained model was extracted to form features with identical spatial coverage to the spectral bands. The features and the spectral bands together form the input to random forest models to predict field observations of the sediment characteristics such as median grain size and silt content, as well as the macrozoobenthic biomass and species richness. The maximum prediction accuracy of feature-based maps was close to 62% for the sediment characteristics and 37% for benthic fauna indices. The encoded features improved the prediction accuracy of the random forest regressor model by 15% points on average in comparison to using just the spectral bands. Our method enhances the predictive performance of remote sensing, in particular the spatiotemporal dynamics in median grain size and silt content of the sediment thereby contributing to better-informed management of coastal ecosystems.

Objectives The objective of this study is to understand the characteristics and patterns of the first antibiotic prescriptions for children with acute respiratory infections (ARIs) in rural primary healthcare (PHC) in Guangdong province, China.Design Cross-sectional study.Setting and participants We used prescription data generated from the electronic medical record system of 37 township hospitals in two counties of Shaoguan City, Guangdong province. 46 699 first prescriptions for ARIs in children aged 0–18 years were screened from 444 979 outpatient prescriptions recorded between November 2017 and October 2018.Outcome measures Descriptive analyses were used to report sociodemographic characteristics and antibiotic prescribing profiles. χ2 analysis and binary logistic regression were used to analyse the factors associated with antibiotic prescriptions in children.Results Of the 46 699 sampled cases, 83.00% (n=38 759) received at least one antibiotic as part of their first prescription. Of the 38 759 sampled cases treated with antibiotics, 40.76% (n=15 799), 56.15% (n=21 762) and 31.59% (n=12 244) received parenteral antibiotics, broad-spectrum antibiotics and two or more kinds of antibiotics, respectively. Multivariable analysis showed that children aged ≤5 years were less likely to be prescribed with antibiotics than those aged 16–18 years (OR 0.545, p

This study introduces a machine learning-based framework for mapping street patterns in urban morphology, offering an objective, scalable approach that transcends traditional methodologies. Focusing on six diverse cities, the research employed supervised machine learning to classify street networks into gridiron, organic, hybrid, and cul-de-sac patterns with the street-based local area (SLA) as the unit of analysis. Utilising quantitative street metrics and GIS, the study analysed the urban form through the random forest method, which reveals the predictive features of urban patterns and enables a deeper understanding of the spatial structures of cities. The findings showed distinctive spatial structures, such as ring formations and urban cores, indicating stages of urban development and socioeconomic narratives. It also showed that the unit of analysis has a major impact on the identification and study of street patterns. Concluding that machine learning is a critical tool in urban morphology, the research suggests that future studies should expand this framework to include more cities and urban elements. This would enhance the predictive modelling of urban growth and inform sustainable, human-centric urban planning. The implications of this study are significant for policymakers and urban planners seeking to harness data-driven insights for the development of cities.

The structural, mechanical, and electronic properties of cubic Cr0.5-xAl0.5TMxN, doped with TM (transition metal) elements (TM = Ti, V, Y, Zr, Hf, and Ta) at low concentrations (x = 0.03 and 0.06), was investigated by first-principles calculations. The results of the structural properties calculations reveal that the addition of Ti, Y, Hf, Zr, and Ta expand the volume, while V has the opposite effect. All doped compounds are thermodynamically stable, and Cr0.5-xAl0.5TMxN with TM = Ti is energetically more favorable than other doped compounds. At the same doping concentration, Cr0.5-xAl0.5VxN possesses the highest stiffness, hardness, and resistance to external forces due to its greatest mechanical properties, and Cr0.5-xAl0.5TaxN possesses the highest elastic anisotropy and the lowest Young’s modulus. Substituting Cr atoms with TM atoms in a stepwise manner results in a decrease in the bulk modulus, shear modulus, Young’s modulus, and theoretical hardness of Cr0.5-xAl0.5TMxN, while increasing its toughness. Based on the calculation results of the total and partial density of states of Cr0.5Al0.5N and Cr0.47Al0.5TM0.03N, all compounds exhibit metallic behavior as indicated by the finite density of states at the Fermi level. The contribution of Ti-3d, V-3d, and Ta-3d orbitals at Fermi level is significantly higher than that of other TM atoms, resulting in a more pronounced metallic character for Cr0.47Al0.5Ti0.03N, Cr0.47Al0.5V0.03N, and Cr0.47Al0.5Ta0.03N.

The full-field strain of rock material under dynamic compression load was studied using the high-speed three dimensional digital image correlation (3D-DIC) method. The dynamic test was conducted on Laizhou granite using a split Hopkinson pressure bar (SHPB) method. Wave propagation, dispersion and radial inertial effect on the specimen were found by DIC results. A recovery of strain in the post-peak stage was detected on the specimen by DIC, which was unrevealed in the traditional one-dimensional theory method. It can be found that the strain measured by strain gauge was a calculated average one, whereas the strain measured by 3D-DIC could reflect more variation details. Specifically, the testing principle with impact loads and rock dynamic behavior was re-examined using stress wave propagation theory. The theoretical results showed that the specimen reached equilibrium after a series of wave reflections and transmissions and its stress was infinitely close to the initial value of 109.2 MPa. Moreover, the specimen had the calculated maximum strain of 0.52% and strain rate of 15.11 s−1, improving the reasonable agreement with the experimental results and requirements of rock mechanical properties measured by SHPB technology.

Traditional explosives have characteristics of high risk, large vibration, and poor directional fracturing. Consequently, an instantaneous expander with a single crack surface (IESCS), which is a novel non-explosive directional rock-breaking technique, has been developed. The directional roof-cutting mechanism of the IESCS method, driven by high-pressure gas, was theoretically analyzed. Laboratory experiments and numerical simulations proved the directional slitting effect of the IESCS method to be excellent. Compared with shaped-charge blasting, the charge of IESCS was reduced by 8.9%, but the crack rate increased by 9% in field tests. After IESCS pre-splitting, the roof directionally collapsed along the cutting line, and the gangue filled the goaf. Moreover, the directional roof cutting by the IESCS could decrease roadway stress. The average pressure of hydraulic supports on the cutting side of the roof was 31% lower than that on the non-cutting side of the roof after pre-splitting. After the self-formed roadway constructed by the IESCS was stabilized, the final relative displacement of the roof and floor was 157.3 mm, meeting the required standard of the next working face. Thus, the IESCS was effectively applied to directional roof pre-splitting. The results demonstrate the promising potential of IESCS in the mining and geotechnical fields.

Due to properties of reducing impact，improving uneven load，and lowering noise in the meshing process，the technology of tooth surface modified are very common in the wind power gear. As the last process of machining gear，form grinding determines the accuracy of gear directly. Therefore，solving geometry error of form grinding becomes vital for optimize grinding tool path and enhancing the machining precision. Thus，this paper builds a model of geometrical error. In order to solve the geometry error of form grinding， firstly， tooth surface model of gears combining the profile and axial modification （including drum and helix modification） is constructed. Then，based on the tooth surface parameter，the length of common perpendicular between axes of the gear and the wheel，the contacting curve between the gear and the wheel is solved. The form grinding tooth surface is constructed. Finally，the geometrical error of tooth surfuce form grinding is defined by using the theoretical tooth surface and form grinding tooth surface， the geometric error model of tooth surface form grinding is established， some suggestions are given to reduce the geometry error of form grinding.

This study investigates the establishment of the Yangtze River Delta Eco-Green Integrated Development Demonstration Zone (also known as Ecological Demonstration Zone). During the inspection and acceptance process of the higher-level government, the authors identified two distinct types of government cooperation between frontline environmental policy implementers and middle-level government, as well as the public. The new interaction emphasizes cooperation between implementers and the public, while the traditional interaction involves collaboration between implementers and the government. This research aims to comprehend the underlying reasons for the shift in the targeted interaction of frontline government in environmental governance. The study uses fuzzy-set qualitative comparative analysis to explore the cooperation dynamics in the implementation of environmental policies and to uncover that the power to promote the interaction of frontline governments in environmental governance comes from institutional change factors such as fuzzy task models and qualitative on-site inspections and acceptances by higher-level governments.

This article presents an integrated approach for theoretical analysis and numerical modeling to investigate the mechanism of roof presplitting and its reasonable parameters in the hard roof and longwall top-coal caving face. The test site is located in the city of Jinzhong, Shanxi Province, China. The theoretical analysis results indicated that when the presplitting angle remains constant, the tensile stress at the unpenetrated surface is approximately exponentially distributed with the presplitting height. When the presplitting height remains constant, the variation curve of tensile stress at the unpenetrated surface with the presplitting angle is parabolic. As the presplitting height increases, the presplitting angle required for the tensile stress at the unpenetrated face to exceed the ultimate tensile strength of limestone first increases and then decreases. The ground response of retained entry obtained with numerical modeling confirmed the theoretical analysis results. Meanwhile, numerical modeling results also showed that presplitting height affects the volume of the collapse gangues and the structure of the overlying strata above the retained entry. The presplitting angle is effective in reducing the frictional resistance between the collapse gangue and roof structure of retained entry. Moreover, based on the ground response of the retained entries, the reasonable parameters of the roof presplitting were determined at 17 m and 15°. The field application showed that reasonable roof presplitting parameters could achieve satisfactory effects at pressure relief and retained entry in the longwall top-coal caving panel. Furthermore, the proposed design principle of the roof presplitting technique can be applied to other projects.

In order to investigate the influence of sepiolite minerals on the normal force of magnetorheological grease (MRG), a mixed sample (ALCH) on the basis of preparing an aluminum–lithium-based magnetorheological grease (base sample ALC), containing sepiolite was further prepared. The field-dependent normal force of the two samples was tested using a rotational rheometer, considering conditions such as magnetic field, time, strain amplitude, frequency, and temperature, and the results were compared. The results indicate that sepiolite limits the field dependent normal force of the magnetorheological grease under steady state shear, and is unaffected by magnetic field, time, temperature, and shear rate. Sepiolite has minimal impact on the transient response of the magnetorheological grease. Under oscillatory shear, the magnetic field is an important factor influencing the field-dependent normal force response of the sepiolite-magnetorheological grease (ALCH). At low magnetic fields, the field-dependent normal force of the sepiolite-containing sample (ALCH) is greater than that of the base sample (ALC), while this relationship is reversed at high magnetic fields, unaffected by other factors. Under long-term shear conditions, both samples exhibit good shear stability, as well as consistency at different frequencies and strain amplitudes. However, an increase in shear rate reduces the normal force, and temperature also affects the field-dependent normal force. The patterns of variation in steady-state and oscillatory shear modes are not entirely the same, but both exhibit a characteristic decrease with increasing temperature under high magnetic field intensities. Sepiolite can reduce the temperature sensitivity of the normal force of the magnetorheological grease. In conclusion, the introduction of sepiolite is beneficial for the application of magnetorheology in high-precision devices.

Background: Studies have shown that glutathione S-transferase M1 (GSTM1) and. glutathione S-transferase T1 (GSTT1) null genotype may increase the risk of cervical cancer (CC) or ovarian cancer (OC), however, the results of published original studies and meta-analyses are inconsistent.Objectives: To investigate the association between GSTM1 present/null and GSTT1 present/null polymorphisms, with the risk of cervical cancer or ovarian cancer.Methods: The odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the association between GSTM1 present/null and GSTT1 present/null polymorphisms and the risk of cervical cancer or ovarian cancer. To assess the confidence of statistically significant associations, we applied false positive reporting probability (FPRP) and bayesian false discovery probability (BFDP) tests.Results: Overall analysis showed that GSTM1 null was associated with an increased risk of cervical cancer, and subgroup analysis showed a significant increase in cervical cancer risk in Indian and Chinese populations; GSTT1 was not found null genotype are significantly associated with cervical cancer. Overall analysis showed that GSTM1 and GSTT1 null were not associated with the risk of ovarian cancer, subgroup analysis showed that GSTM1 null was associated with an increased risk of OC in East Asia, and GSTT1 null was associated with an increased risk of OC in South America. However, when we used false positive reporting probability and bayesian false discovery probability to verify the confidence of a significant association, all positive results showed “low confidence” (FPRP > .2, BFDP > .8).Conclusion: Overall, this study strongly suggests that all positive results should be interpreted with caution and are likely a result of missing plausibility rather than a true association.

The very first influenza virus exposure in a human during infancy is known to imprint the host immune system. However, it is unclear how the memory B cells that first target virus epitopes affect antibody response to the stalk of hemagglutinin (HA) domain of influenza virus. Our study is designed to measure the cross-reactivity of antibodies induced by inactivated H7N9 virus using isolated human peripheral blood B cells. Most of the participants displayed higher levels of plasma IgG against the seasonal strains A/Vic11 and A/Cali09 than those binding to historical outbreak A/HK68 and A/PR8. H3 stalk-binding antibodies were detected in plasma at a 1:5000 dilution in 12 of 13 donors, H1 stalk-binding antibodies in all donors, indicating the existence of H3 and H1 stalk-reactive memory B cells. A moderate to high level of broadly cross-reactive antibodies was induced in memory B cells from all donors after in vitro stimulation of B cells with H7N9 virus. H3 stalk-binding antibodies were also detected in most subjects, with cross-reactivity to H1 and H7 stalk domains. The stalk-reactive antibodies bound to five H3 strains spanning 45 years and different H1, H2, H3, H5, H6, H7, H9 and B strains. Interestingly, H1- and H3-reactive IgG were much higher than H7-binding antibodies after 6 days of H7N9 stimulation. Our results demonstrate that HA stalk-reactive antibodies induced by H7N9 viruses more efficiently bound to yearly circulating both H3N2 and H1N1 strains than the boosting strain, indicating that HA stalk immunological imprint can be extended across currently circulating strains or vaccines.

In the mining of close coal seam, the stress concentration under the residual coal pillar in the upper coal seam leads to serious deformation to roadway surrounding rock in the lower coal seam. Hence, it poses a huge challenge to the maintenance of entry surrounding rock. Based on this, an approach of entry surrounding rock control technology, directional pre-splitting, and roof-cutting pressure relief, was applied. The stress and deformation of entry surrounding rock utilizing directional pre-splitting and roof-cutting pressure relief were studied by numerical simulation and field test The results indicated that the depth of stress concentration under the residual coal pillar achieve 44 m. With the application of the roof presplitting, the vertical stress of the entry roof decreased. Utilizing the roof presplitting with a height of 7 m and an angle of 15°, the gangue filled the goaf and supported the overlying strata. Meanwhile, the surrounding rock of entry was controlled with a constant resistance anchor cable (9 m length) and gangue prevention support structure. Through field test monitoring, the roof pressure and the deformation of surrounding rock increases rapidly at 30 ∼ 110 m behind the working face. From 110 ∼ 160 m, the increased rate of roof pressure and surrounding rock deformation gradually slows down and tends to be stable at 160 m behind the working face. The maximum displacement of the roof to the floor is 511 mm, and the maximum displacement of the gangue rock wall to coal wall is 421 mm. The remaining roadway meets the demand of the adjacent working face.

AbstractDynamic impact tests of negative Poisson’s ratio (NPR) and rebar bolts under different impact wavelengths were carried out using a self-developed NPR bolt tensile impact test system. Additionally, a field anti-impact test using blasting was performed to simulate rockburst, and the field anti-impact characteristics of the NPR and conventional cable were compared and analysed. The experimental test results revealed that the peak impact force of the NPR and rebar bolts was inversely proportional to the wavelength. The NPR bolt underwent only constant resistance structural deformation, and the rod body did not break. The rebar bolt body fractured and necked. Under the same impact wavelength, the impact force and elongation of the two bolt types were proportional to the impact velocity. Compared with the greater peak impact force of the rebar bolt, the NPR bolt output structure deformation reduced the peak impact force. At the same impact velocity, as the wavelength increased, the impact force of the NPR bolt decreased rapidly, and the number of peaks also decreased. The impact force peak value of the rebar bolt was high, the impact force-time curve had multipeak characteristics, and no apparent rapid attenuation occurred. The field test results indicated that the NPR cable could produce slip deformation under the action of an explosion impact force to absorb the impact energy and that it had special mechanical properties to maintain a constant resistance. Under the same equivalent blasting impact energy, the conventional cable test section collapsed completely. The NPR cable test section was stable overall, verifying that the NPR cable had better impact-resistance mechanical properties than conventional cable. The research results provide a reliable basis for the effectiveness of NPR bolts/cables in preventing rockbursts.

Uveal melanoma (UVM) is the most common primary intraocular malignancy tumor in adults. Almost 50% of UVM patients develop metastatic disease, and is usually fatal within 1 year. However, the mechanism of etiology remains unclear. The lack of prognostic, diagnostic and therapeutic biomarkers is a main limitation for clinical diagnosis and treatment. The transient receptor potential (TRP) channels play important roles in the occurrence and development of tumors, which may have the potential as a therapeutic target for UVM. This current study aimed to identify the potential effect and function of the TRPs that could provide survival prediction and new insight into therapy for UVM. Based on the transcriptome data and potential key genes of UVM were screened using the Cancer Genome Atlas (TCGA) databases, Gene expression analysis showed the expression of TRPM4, TRPV2 and other TRPs was high levels in UVM. Using survival analysis, we screened out that the high expression of TRPM4 and TRPV2 was negatively correlated with the prognosis of UVM patients. Cox regression analysis and functional enrichment analysis further indicated that TRPM4 and TRPV2 were the most convincing therapeutic targets of UVM, and the majority of genes involved in ferroptosis pathways in UVM showed positively correlated with the expression levels of TRPM4 and TRPV2. In conclusion, TRPM4 and TRPV2 were considered as two novel prognostic biomarkers and a promising targeted therapy in UVM.

Nanostructured Guinier–Preston (GP) zones are critical for the strength of Al-Mg-Si(-Cu) aluminum alloys. However, there are controversial reports about the structure and growth mechanism of GP zones. In this study, we construct several atomic configurations of GP zones according to the previous research. Then first-principles calculations based on density functional theory were used to investigate the relatively stable atomic structure and GP-zones growth mechanism. The results show that on the (100) plane, GP zones consist of {MgSi} atomic layers without Al atoms, and the size tends to grow up to 2 nm. Along the (100) growth direction, even numbers of {MgSi} atomic layers are more energetically favorable and there exist Al atomic layers to relieve the lattice strain. {MgSi}2Al4 is the most energetically favorable GP-zones configuration, and the substitution sequence of Cu atoms in {MgSi}2Al4 during the aging process is Al → Si → Mg. The growth of GP zones is accompanied by the increase in Mg and Si solute atoms and the decrease in Al atoms. Point defects, such as Cu atoms and vacancies, exhibit different occupation tendencies in GP zones: Cu atoms tend to segregate in the Al layer near the GP zones, while vacancies tend to be captured by the GP zones.

Abstract As the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to threaten public health worldwide, the development of effective interventions is urgently needed. Neutralizing antibodies (nAbs) have great potential for the prevention and treatment of SARS-CoV-2 infection. In this study, ten nAbs were isolated from two phage-display immune libraries constructed from the pooled PBMCs of eight COVID-19 convalescent patients. Eight of them, consisting of heavy chains encoded by the immunoglobulin heavy-chain gene-variable region (IGHV)3-66 or IGHV3-53 genes, recognized the same epitope on the receptor-binding domain (RBD), while the remaining two bound to different epitopes. Among the ten antibodies, 2B11 exhibited the highest affinity and neutralization potency against the original wild-type (WT) SARS-CoV-2 virus (KD = 4.76 nM for the S1 protein, IC50 = 6 ng/mL for pseudoviruses, and IC50 = 1 ng/mL for authentic viruses), and potent neutralizing ability against B.1.1.7 pseudoviruses. Furthermore, 1E10, targeting a distinct epitope on RBD, exhibited different neutralization efficiency against WT SARS-CoV-2 and its variants B.1.1.7, B.1.351, and P.1. The crystal structure of the 2B11–RBD complexes revealed that the epitope of 2B11 highly overlaps with the ACE2-binding site. The in vivo experiment of 2B11 using AdV5-hACE2-transduced mice showed encouraging therapeutic and prophylactic efficacy against SARS-CoV-2. Taken together, our results suggest that the highly potent SARS-CoV-2-neutralizing antibody, 2B11, could be used against the WT SARS-CoV-2 and B.1.1.7 variant, or in combination with a different epitope-targeted neutralizing antibody, such as 1E10, against SARS-CoV-2 variants.

Overuse and inappropriate use of antibiotics are important contributors to bacterial antimicrobial resistance (AMR), especially in ambulatory primary healthcare (PHC) settings in low- and middle-income countries. This study aimed to investigate antibiotic prescription patterns among patients with acute respiratory infections (ARIs) in rural PHC facilities in the Guangdong Province, China. A total of 444,979 outpatient prescriptions were extracted from the electronic medical record system of 35 township health centers (THCs) and 2 community health centers (CHCs) between November 2017 and October 2018. We used the chi-square test to analyze the antibiotic prescription patterns and binary logistic regression to explore patient-related factors associated with antibiotic prescriptions. Of the 162,742 ARI prescriptions, 85.57% (n = 139,259) included at least one antibiotic. Among the 139,259 prescriptions with antibiotics, 37.82% (n = 52,666) included two or more antibiotics, 55.29% (n = 76,993) included parenteral antibiotics, and 56.62% (n = 78,852) included Watch group antibiotics. The binary logistic regression indicated that (1) female patients were slightly less likely to be prescribed antibiotics than males (adjusted odds ratio (OR) = 0.954, 95% confidence interval [CI] [0.928–0.981]; p = 0.001); and (2) compared to patients aged ≤5 years, those who were 6–15 years old (adjusted OR = 1.907, 95% CI [1.840–1.978]; p < 0.001), 16–60 years old (adjusted OR = 1.849, 95% CI [1.785–1.916]; p < 0.001), and >60 years old (adjusted OR = 1.915, 95% CI [1.810–2.026]; p < 0.001) were more likely to be prescribed antibiotics. The overuse and irrational use of antibiotics in PHC settings remain major healthcare challenges in rural Guangdong. Thus, it is imperative to implement targeted antimicrobial stewardship (AMS) policies to address this problem.

Ceftazidime-avibactam (CAZ-AVI) shows promising activity against carbapenem-resistant Klebsiella pneumoniae (CRKP), however, CAZ-AVI resistance have emerged recently. Mutations in KPCs, porins OmpK35 and/or OmpK36, and PBPs are known to contribute to the resistance to CAZ-AVI in CRKP. To identify novel CAZ-AVI resistance mechanism, we generated 10 CAZ-AVI-resistant strains from 14 CAZ-AVI susceptible KPC-producing K. pneumoniae (KPC-Kp) strains through in vitro multipassage resistance selection using low concentrations of CAZ-AVI. Comparative genomic analysis for the original and derived mutants identified CAZ-AVI resistance-associated mutations in KPCs, PBP3 (encoded by ftsI), and LamB, an outer membrane maltoporin. CAZ-AVI susceptible KPC-Kp strains became resistant when complemented with mutated blaKPC genes. Complementation experiments also showed that a plasmid borne copy of wild-type lamB or ftsI gene reduced the MIC value of CAZ-AVI in the induced resistant strains. In addition, blaKPC expression level increased in four of the six CAZ-AVI-resistant strains without KPC mutations, indicating a probable association between increased blaKPC expression and increased resistance in these strains. In conclusion, we here identified a novel mechanism of CAZ-AVI resistance associated with mutations in porin LamB in KPC-Kp.

Ammonia is commonly produced via the Haber−Bosch process, which is energy intensive with emission of substantial greenhouse gases. As one alternative method, electrochemical nitrogen reduction reaction (NRR) can be driven by the renewable energy and realized at ambient conditions for sustainable NH3 synthesis. However, the reaction suffers from high overpotentials and low selectivity due to the potential overlap with competing proton reduction. As inspired by the natural nitrogenase enzymes, Mo sites are particularly investigated to exhibit the potential for catalyzing NRR. Herein, the recent progresses in modifying Mo‐based catalysts toward enhanced NRR performance are discussed. The modification strategies vary from tuning of metal cores, coordination spheres, and assembled structures. The modification strategies can both efficiently tune the chemisorption energy and geometry of N2, as well as hydrogenated N derivatives on the Mo sites.

AbstractRockbursts are common geological disasters in underground engineering, and rockburst proneness evaluation is an important research subject. In this study, a multidimensional cloud model was used to evaluate the rockburst proneness level, and the control variable method was used to establish 15 multidimensional cloud (MC) models. The key factors affecting the accuracy of multidimensional cloud model evaluation are numerical characteristics, weight, and normalization methods. The optimal numerical characteristics calculation method of a multidimensional cloud model was determined, and an improved CRITIC (IC) weight method was optimised by introducing the relative standard deviation and an improved quantisation coefficient. Six rockburst indexes were used as input for the multidimensional cloud model, including the elastic deformation energy index Wet, maximum tangential stress σθMPa of a cavern, uniaxial compressive strength σcMPa, uniaxial tensile strength στMPa, strength brittleness coefficient B1=σc/στ, and stress coefficient σθ/σc. The model was used to learn 271 groups of complete rockburst cases, and the MC-IC rockburst proneness evaluation method was established. The performance of the proposed MC-IC rockburst proneness method was verified by an 8-fold cross-validation and confusion matrix (precision, recall, F1). The method was tested to evaluate 20 groups of rockburst cases from the Jiangbian Hydropower Station, and the accuracy reaches 95%. The evaluation results were compared with three empirical criteria: four cloud-based methods, three unsupervised learning methods, and four supervised learning methods; the accuracy of the method established in this paper is 93.33%. The results showed that the MC-IC method had an excellent performance in evaluating rockburst proneness and can provide a practical basis for identifying rockburst hazard areas in deep engineering.

Hydrodynamic cavitation has been investigated extensively in the field of water treatment in the last decade and a well-designed hydrodynamic cavitation reactor is critical to the efficient removal of algal and large-scale application. In this paper, a jet pump cavitation reactor (JPCR) is developed for the removal of cyanobacteria Microcystis aeruginos in a pilot scale. The results demonstrate that the photosynthetic activity of M. aeruginosa is greatly inhibited immediately after treatment in the JPCR, and the growth is also hindered after 3 days culture. Moreover, a high cell disruptions of M. aeruginosa is detected after treated by JPCR. The release of chlorophyll-a indicates that the JPCR caused serious rupture to M. aeruginosa cells. The plausible cell disruption mechanisms are proposed in accordance with a fluorescence microscope and scanning electron microscope. Then, the optimization of cell disruption efficiency is also investigated for various operating conditions. The results showed that the algal cell disruption efficiency is improved at higher inlet pressure and the cavitation stage between the unstable limited operation cavitation stage and stable limited operation cavitation stage. The effect and optimization of JPCR on algal reduction are highlighted. The results of the study promote the application of hydrodynamic cavitation on algal removal and provide strong support for JPCR application in algal removal.

Abstract Background LncRNA WT1-AS is a recently identified potential tumor suppressor in gastric cancer. This study mainly explored the role of WT1-AS in non-small cell lung cancer (NSCLC). Methods WT1-AS and TGF-β1 mRNA in two types of tissues of 74 NSCLC patients were detected by performing RT-qPCR experiments. WT1-AS and TGF-β1 expression vectors were established using the pcDNA3.1 vector. Protein concentration was measured by BCA assay. Mean values in this study were calculated using the data of three biological replicates of each experiment. Results We found that WT1-AS was down-regulated, while TGF-β1 was upregulated in NSCLC tissues. Survival analysis showed that low levels of WT1-AS expression predicted poor survival of NSCLC patients. WT1-AS and TGF-β1 were inversely correlated in NSCLC tissues. Over-expression experiments revealed down-regulated TGF-β1 after WT1-AS over-expression, while TGF-β1 over-expression failed to affect WT1-AS. WT1-AS over-expression resulted in inhibited cancer cell stemness. TGF-β1 over-expression played an opposite role and attenuated the effects of TGF-β1 over-expression. Conclusion Therefore, WT1-AS over-expression may inhibit non-small cell lung cancer cell stemness by down-regulating TGF-β1. Trial registration The First Affiliated Hospital of Anhui Medical University Ethics committee approved this study (AHMU20101009).

Abstract Background Hypoxia is a potent molecular signal for cellular metabolism, mitochondrial function, and migration. Conditions of low oxygen tension trigger regulatory cascades mediated via the highly conserved HIF-1 α post-translational modification system. In the adaptive immune response, B cells (Bc) are activated and differentiate under hypoxic conditions within lymph node germinal centers, and subsequently migrate to other compartments. During migration, they traverse through changing oxygen levels, ranging from 1-5% in the lymph node to 5-13% in the peripheral blood. Interestingly, the calcineurin inhibitor cyclosporine A is known to stimulate prolyl hydroxylase activity, resulting in HIF-1 α destabilization and may alter Bc responses directly. Over 60% of patients taking calcineurin immunosuppressant medications have hypo-gammaglobulinemia and poor vaccine responses, putting them at high risk of infection with significantly increased morbidity and mortality. Results We demonstrate that O 2 tension is a previously unrecognized Bc regulatory switch, altering CXCR4 and CXCR5 chemokine receptor signaling in activated Bc through HIF-1 α expression, and controlling critical aspects of Bc migration. Our data demonstrate that calcineurin inhibition hinders this O 2 regulatory switch in primary human Bc. Conclusion This previously unrecognized effect of calcineurin inhibition directly on human Bc has significant and direct clinical implications.

The connectivity restoration has significance for Industrial IoTs (IIoTs). If the connectivity is compromised, mobile data collectors can be deployed to restore the connectivity. The aggregation ratio, which is the proportion of data successfully delivered to the sink over all data, is considered as a crucial index. However, previous works only consider the travel distance, the load balance, the latency and the energy cost over the aggregation ratio. In this paper, a machine learning based connectivity restoration strategy CRrbf, that utilizes a Radial Basis Function Neural Network (RBFNN) along with an Unscented Kalman Filter (UKF), is proposed to maximize the aggregation ratio meanwhile reduce the energy cost. The theoretical analysis and simulation results indicate that CRrbf outperforms both distance based strategies and terrain based strategies in the aggregation ratio, the network latency and the network throughput. And the energy cost of CRrbf is less than that of distance based strategies.

Many rigorous studies have shown that early childhood infections leave a lasting imprint on the immune system. The understanding of this phenomenon has expanded significantly since 1960, when Dr. Thomas Francis Jr first coined the term “original antigenic sin”, to account for all previous pathogen exposures, rather than only the first. Now more commonly referred to as “immune imprinting”, this effect most often focuses on how memory B-cell responses are shaped by prior antigen exposure, and the resultant antibodies produced after subsequent exposure to antigenically similar pathogens. Although imprinting was originally observed within the context of influenza viral infection, it has since been applied to the pandemic coronavirus SARS-CoV-2. To fully comprehend how imprinting affects the evolution of antibody responses, it is necessary to compare responses elicited by pathogenic strains that are both antigenically similar and dissimilar to strains encountered previously. To accomplish this, we must be able to measure the antigenic distance between strains, which can be easily accomplished using data from multidimensional immunological assays. The knowledge of imprinting, combined with antigenic distance measures, may allow for improvements in vaccine design and development for both influenza and SARS-CoV-2 viruses.

New Delhi metallo-β-lactamase (NDM)-carrying IncX3 plasmids is important in the transmission of carbapenem resistance in Escherichia coli. Fitness costs related to plasmid carriage are expected to limit gene exchange; however, the causes of these fitness costs are poorly understood. Compensatory mutations are believed to ameliorate plasmid fitness costs and enable the plasmid’s wide spread, suggesting that such costs are caused by specific plasmid–host genetic conflicts. By combining conjugation tests and experimental evolution with comparative genetic analysis, we showed here that the fitness costs related to ndm/IncX3 plasmids in E. coli C600 are caused by co-mutations of multiple host chromosomal genes related to sugar metabolism and cell membrane function. Adaptive evolution revealed that mutations in genes associated with oxidative stress, nucleotide and short-chain fatty acid metabolism, and cell membranes ameliorated the costs associated with plasmid carriage. Specific genetic conflicts associated with the ndm/IncX3 plasmid in E. coli C600 involve metabolism and cell-membrane-related genes, which could be ameliorated by compensatory mutations. Collectively, our findings could explain the wide spread of IncX3 plasmids in bacterial genomes, despite their potential cost.

Introduction: Recently, volumetric absorptive microsampling (VAMS) has been used for accurate sampling of a fixed peripheral blood volume (10 µL) on a volumetric swab, and long-term sample storage. The mPlex-Flu assay is a novel, high-throughput assay that simultaneously measures the concentration of antibodies against the hemagglutinin (HA) proteins from multiple influenza virus strains with ≤5 µL of serum. Here we describe combining these two methods to measure multidimensional anti-influenza IgG activity in whole blood samples collected by a finger stick and VAMS, with correction for serum volume based on simultaneous hemoglobin measurement. Methods: We compared capillary blood samples obtained from a finger stick using a VAMS device with serum samples collected by traditional phlebotomy from 20 subjects, with the influenza antibody profiles measured by the mPlex-Flu assay. Results: We found that results with the two sampling methods were highly correlated within subjects and across all influenza strains (mean R2 = 0.9470). Adjustment for serum volume, based on hemaglobin measurement, was used to estimate serum volume of samples and improved the accuracy. IgG measurements were stable over 3 weeks when VAMS samples were stored at room temperature or transported using a variety of shipping methods. Additionally, when volunteers performed finger-stick VAMS at-home by themselves, the comparison results of anti-HA antibody concentrations were highly consistent with sampling performed by study personnel on-site (R2 = 0.9496). Conclusions: This novel approach can provide a simple, accurate, and low-cost means for monitoring the IgG anti-influenza HA antibody responses in large population studies and clinical trials.

IncX3 plasmids are correlated with the dissemination and acquisition of carbapenem resistance in Enterobacteriaceae and have been prevalent in China over the last 10 years. Since the distribution characteristics of IncX3 plasmids across China as well as their evolutionary traits for 10 years remain unclear, here we conducted a retrospective literature review and in silico comparative analysis of IncX3 plasmids in publicly available IncX3 plasmid genomes. IncX3 plasmids distributed in 17 provinces or cities were extracted for analysis, which tend to be specifically associated with hospital-isolated Escherichia coli ST410 from phylogroup A. Although the backbones of IncX3 plasmids have remained highly conservative over the last 10 years, the blaNDM resistance genetic contexts on these plasmids could fall into five subtypes, among which AR_N1_I has been identified in Enterobacter cloacae174 chromosome and AR_N5_I was simultaneously located on IncF and IncA/C plasmids. This suggests that the blaNDM resistance gene environment can spread between different plasmids, between different bacterial genera, or between strains and plasmids, highlighting that it is imperative to adopt more stringent infection control measures targeting IncX3 plasmid spread.

Dengue fever is regarded as the most prevalent mosquito-borne viral disease in humans. However, information of dengue virus (DENV) infection in pregnant women and the influence factors remain unclear. In this study, we extracted information of 2,076 pregnant women from the Prenatal Environment and Offspring Health (PEOH) birth cohort conducted since 2016 in Guangzhou, China. Peripheral blood and clean midstream urine samples of participants were collected during their hospitalization for childbirth. Indirect enzyme-linked immunosorbent assay (ELISA) was used to detect immunoglobulin G (IgG) antibodies of DENV in serum samples, and inductively coupled plasma mass spectrometry (ICP-MS) was applied to determine the Fe concentrations in the urine samples, which were then adjusted for by urine creatinine and transformed by natural logarithm (ln-Fe). The seroprevalence of DENV IgG antibody in all included participants was 2.22% (46/2,076). We observed higher seroprevalence of IgG antibody in women aged ≥35 years (2.9%), education ≤ 12 years (2.5%), yearly income per capita

Antibody production following vaccination can provide protective immunity to subsequent infection by pathogens such as influenza viruses. However, circumstances where antibody formation is impaired after vaccination, such as in older people, require us to better understand the cellular and molecular mechanisms that underpin successful vaccination in order to improve vaccine design for at-risk groups. Here, by studying the breadth of anti-haemagglutinin (HA) IgG, serum cytokines, and B and T cell responses by flow cytometry before and after influenza vaccination, we show that formation of circulating T follicular helper (cTfh) cells was associated with high-titre antibody responses. Using Major Histocompatability Complex (MHC) class II tetramers, we demonstrate that HA-specific cTfh cells can derive from pre-existing memory CD4+ T cells and have a diverse T cell receptor (TCR) repertoire. In older people, the differentiation of HA-specific cells into cTfh cells was impaired. This age-dependent defect in cTfh cell formation was not due to a contraction of the TCR repertoire, but rather was linked with an increased inflammatory gene signature in cTfh cells. Together, this suggests that strategies that temporarily dampen inflammation at the time of vaccination may be a viable strategy to boost optimal antibody generation upon immunisation of older people.

In this paper, the effect of temperature on rheological properties of magnetorheological (MR) gel is investigated under rotational steady shear and oscillatory dynamic shear. A kind of fluid-like MR gel (MRG) was firstly synthesized by mixing carbonyl iron powder (CIP) with polymer matrix. Then, the relationship between yield stress, normal stress of MRG and shear rate under six temperatures and four magnetic field strengths were studied by rotational shear experiments. The results demonstrate that the dependence of shear stress on temperature displays an opposite tendency in comparison with that of normal stress on temperature. Moreover, maximum yield stress, one of the most important parameter of MR materials, decreases with the increment of temperature. Under oscillatory dynamic shear test, storage and loss moduli and normal stress of MRG all increase with temperature when a magnetic field is applied, which presents a contrary trend in the absence of a magnetic field. Related mechanisms about the alternation of microstructures of MRG were proposed to explain the above-mentioned phenomena. This paper is helpful in fabricating semi-active engineering devices using MR materials as a medium.