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Given the significant decline in vaccine efficacy against Omicron, the development of novel vaccines with specific or broad-spectrum effectiveness is paramount. In this study, we formulated four monovalent vaccines based on recombinant spike trimer proteins, along with three bivalent vaccines, and five monovalent vaccines based on recombinant spike proteins. We evaluated the efficacy of different vaccination regimens in eliciting neutralizing antibodies in mice through pseudovirus neutralization assays. Following two doses of primary immunization with D614G, mice received subsequent immunizations with Omicron (BA.1, BA.2, BA.4/5) boosters individually, which led to the generation of broader and more potent cross-neutralizing activity compared to D614G boosters. Notably, the BA.4/5 booster exhibited superior efficacy. Following two doses of primary immunization with Omicron (BA.1, BA.2, BA.4/5), mice were subsequently immunized with one dose of D614G booster which resulted in broader neutralizing activity compared to one dose of Omicron (BA.1, BA.2, or BA.4/5). In unvaccinated mice, full-course immunization with different bivalent vaccines induced broad neutralizing activity against Omicron and pre-Omicron variants, with D614G&BA.4/5 demonstrating superior efficacy. However, compared to other variants, the neutralizing activity against XBB.1.5/1.9.1 is notably reduced. This observation emphasizes the necessity of timely updates to the vaccine antigen composition. Based on these findings and existing studies, we propose a vaccination strategy aimed at preserving the epitope repertoire to its maximum potential: (1) Individuals previously vaccinated or infected with pre-Omicron variants should inoculate a monovalent vaccine containing Omicron components; (2) Individuals who have only been vaccinated or infected with Omicron should be inoculated a monovalent vaccine containing pre-Omicron variants components; (3) Individuals without SARS-CoV-2 infection and vaccination should inoculate a bivalent vaccine comprising both pre-Omicron and Omicron components for primary immunization. Additionally, through cross-inoculation of SARS-CoV-2 D614G spike trimer protein and SARS-CoV-1 spike protein in mice, we preliminarily demonstrated the possibility of cross-reaction between different coronavirus vaccines to produce resistance to the pan-coronavirus.

According to the latest report by the WHO, cardiovascular disease claims approximately 17.9 million lives annually, making it one of the leading causes of mortality. Hence, early screening and detection of cardiovascular diseases are important for their prevention. Heart sound signals contain a wealth of information on cardiac function and health status. Researchers have recently utilized deep learning methods to detect abnormal features in heart sound signals, thereby facilitating disease diagnosis. Currently, existing heart sound datasets suffer from imbalanced data proportions, complex feature types, and low discriminative power between systolic and diastolic murmurs, resulting in the suboptimal performance of deep learning algorithms in detection. Therefore, we propose a heart sound abnormality detection algorithm based on the Swin Transformer architecture. Firstly, we enhance the ability to extract local texture features of heart sound signals by introducing a convolutional embedding module into the positional encoding layer of the backbone network. Second, we augmented the model’s capability to extract the frequency-domain features of heart-sound signals by incorporating a discrete convolutional mapping structure. This structure utilizes discrete cosine transformation in conjunction with convolutional projection to acquire feature matrices, thereby improving classification accuracy. Finally, we employed a Focal Loss function to prioritize abnormal heart-sound samples, enhancing the generalization ability of the model and evaluating the proposed algorithm using the PhysionNet/CinC 2016 public dataset. The results demonstrated an Accuracy of 93.4%, a Specificity of 90.4% and a Sensitivity of 95.7%.

The emergence and spread of the mobile colistin-resistance gene, mcr-1, and its variants pose a challenge to the use of colistin, a last-resort antibiotic used to treat severe infections caused by extensively drug-resistant (XDR) Gram-negative pathogens. Antibiotic adjuvants are a promising strategy to enhance the efficacy of colistin against colistin-resistant pathogens; however, few studies have considered the effects of adjuvants on limiting resistance-gene transmission. We found that chelerythrine (4 mg∙L−1) derived from Macleaya cordata extract, which is used as an animal feed additive, reduced the minimal inhibitory concentration (MIC) of colistin against an mcr-1 positive Escherichia coli (E. coli) strain by 16-fold (from 2.000 to 0.125 mg∙L−1), eliminated approximately 104 colony-forming units (CFUs) of an mcr-1-carrying strain in a murine intestinal infection model, and inhibited the conjugation of an mcr-1-bearing plasmid in vitro (by > 100-fold) and in a mouse model (by up to 5-fold). A detailed analysis revealed that chelerythrine binds to phospholipids on bacterial membranes and increases cytoplasmic membrane fluidity, thereby impairing respiration, disrupting proton motive force (PMF), generating reactive oxygen species (ROS), and decreasing intracellular adenosine triphosphate (ATP) levels, which subsequently downregulates mcr-1 and conjugation-associated genes. These dual effects of chelerythrine can expand the use of antibiotic adjuvants and may provide a new strategy for circumventing mobile colistin resistance.

Abstract Aiming at the problem of easy misdetection and omission of small targets of long-distance vehicles in detecting vehicles in traffic scenes, an improved YOLOX_S detection model is proposed. Firstly, the redundant part of the original YOLOX_S network structure is clipped using the model compression strategy, which improves the model inference speed while maintaining the detection accuracy; secondly, the Resunit_CA structure is constructed by incorporating the coordinate attention module in the residual structure, which reduces the loss of feature information and improves the attention to the small target features; thirdly, in order to obtain richer small target features, the PAFPN structure tail to add an adaptive feature fusion module, which improves the model detection accuracy; finally, the loss function is optimized in the decoupled head structure, and the Focal Loss loss function is used to alleviate the problem of uneven distribution of positive and negative samples. The experimental results show that compared with the original YOLOX_S model, the improved model proposed in this paper achieves an average detection accuracy of 77.19% on this experimental dataset. However, the detection speed decreases to 29.73 fps, which is still a large room for improvement in detection in real-time. According to the visualization experimental results, it can be seen that the improved model effectively alleviates the problems of small-target missed detection and multi-target occlusion.

Abstract This paper describes an image processing-based technique used to measure the volume of residual water in the drinking water bottle for the laboratory mouse. This technique uses a camera to capture the bottle's image and then processes the image to calculate the volume of water in the bottle. Firstly, the Grabcut method separates the foreground and background to avoid the influence of background on image feature extraction. Then Canny operator was used to detect the edge of the water bottle and the edge of the liquid surface. The cumulative probability Hough detection identified the water bottle edge line segment and the liquid surface line segment from the edge image. Finally, the spatial coordinate system is constructed, and the length of each line segment on the water bottle is calculated by using plane analytical geometry. Then the volume of water is calculated. By comparing image processing time, the pixel number of liquid level, and other indexes, the optimal illuminance and water bottle color were obtained. The experimental results show that the average deviation rate of this method is less than 5%, which significantly improves the accuracy and efficiency of measurement compared with traditional manual measurement.

An embedded core fiber sensor based on surface plasmon resonance (SPR) principle is developed. In the structure of optical fiber, the middle of the optical fiber cladding is hollowed out. The hollowed-out part is then filled with a temperature-sensitive layer. For the temperature sensitive layer, polydimethylsiloxane(PDMS) is chosen. A metal layer is placed outside the cladding of the optical fiber to detect changes in the external environment and stimulate the SPR effect.The gold metal(Au) layer is also placed between the cladding and the PDMS to stimulate the SPR effect.The refractive index of seawater varies with salinity and temperature through COMSOL Multiphysics finite element simulation. We can measure the two parameters of salinity and temperature at the same time based on the SPR principle. The sensitivity of salinity and temperature calculated by this sensor is 0.193 nm/%, 0.397 nm/°C. Fiber optic sensors use the SPR principle to detect dynamic, real-time, continuous processes. The measurement range is very wide, and the brightness is also very high.Compared with single-channel measurement of single parameter, this sensor can greatly improve the efficiency of two-parameter measurement. The sensor has the advantages of simple structure, low production cost and high sensitivity, which can realize the simultaneous measurement of two parameters and avoid the crosstalk between parameters. It has great research significance.

Abstract The volume detection of medical mice feed is crucial to understand the food intake requirements of mice at different growth stages and to grasp their growth, development, and health status. Aiming at the problem of volume calculation in the way of feed bulk in mice, a method for detecting the bulk volume of feed in mice based on binocular stereo vision was proposed. Firstly, the three-dimensional point coordinates of the feed's surface were calculated using the binocular stereo vision three-dimensional reconstruction technology. The coordinates of these dense points formed a point cloud, and then the projection method was used to calculate the volume of the point cloud; and finally, the volume of the mice feed was obtained. We use the stereo matching data set provided by the Middlebury evaluation platform to conduct experimental verification. The results show that our method effectively improves the matching degree of stereo matching and makes the three-dimensional point coordinates of the obtained feed's surface more accurate. The point cloud is then denoised and Delaunay triangulated, and the volume of the tetrahedron obtained after the triangulation is calculated and summed to obtain the total volume. We used different sizes of wood instead of feed for multiple volume calculations, and the average error between the calculated volume and the real volume was 7.12%. The experimental results show that the volume of the remaining feed of mice can be calculated by binocular stereo vision.

An optical fiber sensor for the simultaneous measurement of microdisplacement and temperature based on balloon-shaped single-mode fibers cascaded with a fiber Bragg grating with two core-offset joints is proposed. The interference between the core mode and cladding mode is caused by the stimulation of the cladding mode by the core-offset joints’ structure. The cladding of the core has a distinct refractive index, which causes optical path differences and interference. The balloon-shaped structure realizes mode selection by bending. As the displacement increases, the radius of the balloon-shaped interferometer changes, resulting in a change in the interference fringes of the interferometer, while the Bragg wavelength of the fiber grating remains unchanged. Temperature changes will cause the interference fringes of the interferometer and the Bragg wavelength of the fiber grating to shift. The proposed optical fiber sensor allows for the simultaneous measurement of microdisplacement and temperature. The results of the experiment indicate that the sensitivity of the interferometer to microdisplacement is 0.306 nm/µm in the sensing range of 0 to 200 μm and that the temperature sensitivity is 0.165 nm/°C, respectively. The proposed curvature sensor has the advantages of a compact structure, extensive spectrum of dynamic measurement, high sensitivity, and simple preparation, and has a wide range of potential applications in the fields of structural safety monitoring, aviation industry, and resource exploration.

The study of rockburst criterion is the key to predict the occurrence of rockburst. Based on the energy principle, a new multi-parameter rockburst criterion (RPC) were established. The accuracy and applicability of some typical rockburst engineering examples in China were verified by using some classical rockburst criteria and the newly proposed RPC. The research results show that: RPC comprehensively considers the various stress states of the surrounding rock mass unit, and reflects the integrity factors, mechanical factors, brittleness factors and energy storage factors in the process of rockburst inoculation. Three rockburst classification thresholds (2, 11 and 110) for four grades of none, weak, moderate and severe rockburst were proposed. The prediction and evaluation of rockburst by RPC is basically consistent with the actual situation of rockburst, which can better reflect the overall trend of rockburst failure in deep tunnels.

Investigating the thermal decomposition characteristics and mechanisms of nano- and submicron-aluminized 1,3,5-trinitro-1,3,5-triazine (RDX) is essential to optimize the formulations and improve combustion/detonation efficiencies. However, no research has focused on the microscopic scale of a single aluminized RDX particle. We demonstrate an all-fiber probing method for the violent thermal decomposition of a single nano-aluminized micron-RDX particle, which we address as micro-explosion in this paper. We believe studying micro-explosion will be beneficial to the research of thermal decomposition. In experiments, we first characterize the micro-explosion as a three-step process, i.e., melting, first decomposition, and second decomposition. Then, we measure micro-explosion properties, i.e., shockwave-like flow velocity, initiation energy threshold, and shockwave-like flow pressure. Among the aluminized RDX particles with 0%, 5%, 10%, 15%, 20%, 25%, and 30% surface coverage ratios (SCRs), the sample with 20% surface coverage ratio shows the highest flow velocity and force, which are about 69.9 mm/s and 39.4 μN, respectively. Moreover, the threshold decreases with rising surface coverage ratios, and the mean threshold of 30% surface coverage ratio is 75 μJ. The experimental results prove that the all-fiber micro-explosion probing method is feasible, safe, and robust.

BackgroundOptimizing adjuvant is one of the critical methods to improve the vaccine. 3M-052, a novel TLR7/8 agonist which was designed for slow dissemination at the injection site, has a potential as adjuvant, but its performance as a vaccine adjuvant for SARS-CoV-2 (B.1.617.2) spike protein has not been studied. The present study aimed to evaluate the effect of Alum-3M-052 as an adjuvant to improve mice serum antibody titers and pseudovirus neutralization efficiency.MethodFemale Balb/c mice were immunized 3 times at day 0, 7 and 21 intramuscularly with SARS-CoV-2 (B.1.617.2) spike protein and adjuvant (Alum or Alum-3M-052). Mice serum was collected weekly since day 7. Antibody titers of mice serum anti-SARS-CoV-2 (B.1.617.2) IgG and IgM were detected by ELISA. Inhibition rates of mice serum blocking SARS-CoV-2 (B.1.617.2) spike protein binding to ACE2 were detected by SARS-CoV-2 (B.1.617.2) Inhibitor Screening Kit. Neutralization efficiencies of mice serum against both SARS-CoV-2 (BA.2.12.1) pseudovirus and SARS-CoV-2 (B.1.617.2) pseudovirus were detected by pseudovirus neutralizing assay.ResultSerum of mice immunized by SARS-CoV-2 (B.1.617.2) spike protein adjuvanted with Alum-3M-052 had highest antibody titers and higher neutralization efficiency against both SARS-CoV-2 (BA.2.12.1) pseudovirus and SARS-CoV-2 (B.1.617.2) pseudovirus. Besides, neutralization efficiency of anti-SARS-CoV-2 (B.1.617.2) spike protein antibody against SARS-CoV-2 (BA.2.12.1) pseudovirus was lower than that of SARS-CoV-2 (B.1.617.2) pseudovirus.ConclusionAlum-3M-052 rapidly increased the titer of anti-SARS-CoV-2 (B.1.617.2) spike protein neutralizing antibodies and enhanced the neutralization ability against pseudoviruses and variants. This study provided evidence for the application of Alum-3M-052 as an adjuvant in COVID-19 vaccines production.

PurposeRecent neuroimaging reports have shown the microstructural changes in coronary artery disease (CAD) and its correlation with cognitive dysfunction while little is known about the functional characteristics of CAD. We hypothesize that functional characteristics may give clues to underlying pathology in CAD and its link with cognitive dysfunction. Degree centrality (DC), a graph-based assessment of network organization was performed to explore the neural connectivity changes in CAD patients compared with healthy controls and their correlation with cognitive measures.MethodsThirty CAD patients and 36 healthy controls were included in our study. All participants underwent functional magnetic resonance imaging (fMRI) of the brain. We performed DC analysis to identify voxels that showed changes in whole-brain functional connectivity with other voxels. DC was measured by the fMRI graph method and comparisons between the two groups were done. All participants underwent neuropsychological assessment (Montreal Cognitive Assessment, MoCA and Mini-Mental State Examination, MMSE).ResultsOur data analysis included 30 CAD patients (59.90 ± 7.53 years) and 36 HCs (61.61 ± 6.19 years). CAD patients showed a greater prevalence of white matter lesions using the Fazekas score than healthy controls (P < 0.001). Importantly, CAD patients showed significantly lower (P < 0.001) MoCA and MMSE scores compared with healthy controls. CAD patients showed significantly decreased DC value (P < 0.001) in the right hippocampus (hippocampus_R), right lingual gyrus (lingual_R), and significantly increased DC value (P < 0.001) in the left middle frontal gyrus (Frontal_Mid_L) when compared with healthy controls respectively. DC value in the hippocampus_R significantly correlated (P < 0.00) with MMSE and MoCA scores in CAD patients. Fazekas scores in CAD patients showed a significant correlation (P < 0.001) with the DC value in the hippocampus_R.ConclusionThese findings suggest that reduced cerebral neural connectivity in CAD may contribute to their cognitive impairment and white matter microstructural damage.

Abstract The SARS‐CoV‐2 Omicron BA.1 variant of concern contains more than 30 mutations in the spike protein, with half of these mutations localized in the receptor‐binding domain (RBD). Emerging evidence suggests that these large number of mutations impact the neutralizing efficacy of vaccines and monoclonal antibodies. We investigated the relative contributions of spike protein and RBD mutations in Omicron BA.1 variants on infectivity, cell–cell fusion, and their sensitivity to neutralization by monoclonal antibodies or vaccinated sera from individuals who received homologous (CoronaVac, SinoPharm) or heterologous (CoronaVac—BNT162b2, BioNTech) and nonhuman primates that received a recombinant RBD protein vaccine. Our data overall reveal that the mutations in the spike protein reduced infectivity and cell–cell fusion compared to the D614G variant. The impaired infectivity and cell–cell fusion were dependent on non‐RBD mutations. We also find reduced sensitivity to neutralization by monoclonal antibodies and vaccinated sera. However, our results also show that nonhuman primates receiving a recombinant RBD protein vaccine show substantial neutralization activity. Our study sheds light on the molecular differences in neutralizing antibody escape by the Omicron BA.1 variant, and highlights the promise of recombinant RBD vaccines in neutralizing the threat posed by the Omicron BA.1 variant.

Although many studies exist on mobile robot path planning, the disadvantages of complex algorithms and many path nodes in logistics warehouses and manufacturing workshops are obvious, mainly due to the inconsistency of map environment construction and pathfinding strategies. In this study, to improve the efficiency of mobile robot path planning, the Delaunay triangulation algorithm was used to process complex obstacles and generate Voronoi points as pathfinding priority nodes. The concept of the grid was used to extract obstacle edges to provide obstacle avoidance strategies for robot pathfinding. Subsequently, the search for priority and regular path nodes used the improved A-star (A*) algorithm. The dynamic fusion pathfinding algorithm (DFPA), based on Delaunay triangulation and improved A*, was designed, which realizes the path planning of mobile robots. MATLAB 2016a was used as the simulation software, to firstly verify the correctness of the DFPA, and then to compare the algorithm with other methods. The results show that under the experimental environment with the same start point, goal point, and number of obstacles, the map construction method and pathfinding strategy proposed in this paper reduce the planned path length of the mobile robot, the number of path nodes, and the cost of overall turn consumption, and increase the success rate of obtaining a path. The new dynamic map construction method and pathfinding strategy have important reference significance for processing chaotic maps, promoting intelligent navigation, and site selection planning.

BackgroundPheochromocytoma-induced cardiomyopathy is a rare but potentially life-threatening complication of pheochromocytoma. It mimics the patterns of stress-induced cardiomyopathy. In severe cases, patients can develop refractory cardiogenic shock, which might require mechanical circulatory support.Case PresentationWe presented a case of 54-year-old female who developed refractory cardiogenic shock, following an elective orthopaedic surgery complicated by cardiac arrest, requiring veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support. After urgent coronary catheterisation revealed normal coronary arteries, further evaluation of the aetiology of cardiogenic shock revealed pheochromocytoma. With a diagnosis of pheochromocytoma-induced cardiomyopathy, the patient had accelerated preoperative alpha adrenergic blockade preparation for a total of 6 days and subsequently had the tumour removed under VA-ECMO support. Postoperatively, the patient recovered well and was off ECMO support and extubated a few days later.The optimal management of pheochromocytoma-induced cardiomyopathy, especially for severe cases, is still unclear. Indeed, some cases will require mechanical circulatory support to allow left ventricular function recovery. But our case also showed that it was possible to introduce alpha blockade safely whilst the patient is on VA-ECMO and has the pheochromocytoma removed with VA-ECMO support after accelerated preoperative preparation.

Growth factors are multi-functional signaling molecules that coordinate multi-stage process of wound healing. During wound healing, growth factors are transmitted to wound environment in a positive and physiologically related way, therefore, there is a broad prospect for studying the mediated healing process through growth factors. However, growth factors (GFs) themselves have disadvantages of instability, short life, rapid inactivation of physiological conditions, low safety and easy degradation, which hinder the clinical use of GFs. Rapid development of delivery strategies for GFs has been trying to solve the instability and insecurity of GFs. Particularly, in recent years, GFs delivered by scaffolds based on biomaterials have become a hotspot in this filed. This review introduces various delivery strategies for growth factors based on new biodegradable materials, especially polysaccharides, which could provide guidance for the development of the delivery strategies for growth factors in clinic.

The objective of this study was to understand the diversity characteristics of ESBL-producing Escherichia coli (ESBL-EC) in chicken, pig, and cattle. A high prevalence of ESBL-EC (260/344) was observed in all food animals with prevalence rates of 78.6% (110/140) for chicken, 70.7% (58/82) for cattle, and 75.4% (92/122) for swine. However, the resistance rates presented significant differences in different animal origin ESBL-EC, where resistance to CTX, GEN, IMP, NEO, and OFL was the highest in chicken ESBL-EC, then in cattle, and the lowest in swine. Seriously, most ESBL-EC harbor multidrug resistance to antibiotics (MDR, ≥3 antibiotic categories), and the MDR rates of ESBL-EC were the highest in chicken (98.18%), followed by swine (93.48%), and the lowest in cow (58.62%), while the same trend also was observed in MDR of ≥5 antibiotic categories. This high prevalence and resistance can be partly interpreted by the high carriage rates of the β-lactamases CTX-M (n = 89), OXA (n = 59), SHV (n = 7), and TEM (n = 259). A significant difference of β-lactamase genes also presented in different animal species isolates, where the chicken origin ESBL-EC possessed higher carriage rates of almost all genes tested than cattle and swine. Notably, eight chicken origin ESBL-EC carried transferable plasmid-mediated blaNDM-1 or blaNDM-5, especially, of which four ESBL-EC also contained the colistin resistance gene mcr-1, as confirmed by genomic analysis. More interestingly, two deletion events with a 500-bp deletion in ΔISAba125 and a 180-bp deletion in dsbC were observed in three blaNDM-5 IncX3 plasmids, which, as far as we know, is the first discovery. This showed the instability and horizontal transfer of blaNDM genetic context, suggesting that blaNDM is evolving to “pack light” to facilitate rapid and stable horizontal transfer. Sequence types (STs) and PFGE showed diversity patterns. The most prevalent STs were ST48 (n = 5), ST189 (n = 5), ST206 (n = 4), ST6396 (n = 3), ST10 (n = 3), and ST155 (n = 3), where ST48 ESBL-EC originated from three food animal species. The STs of all blaNDM-positive ESBL-EC were attributed to three STs, namely, ST6396 (n = 2), ST206 (n = 2), and ST189 (n = 4), where ST189 was also the unique type for four mcr-1-carrying ESBL-EC. In conclusion, we suggest that the three animal species ESBL-EC show similar high prevalence, diversity in isolate lineages, and significant discrepancies in antibiotic resistance and resistance genes. This suggests that monitoring and anti-infection of different food animal origin ESBL-EC need different designs, which deserves more attention and further surveillance.

Abstract Mobile colistin resistance enzyme MCR‐3 is a phosphoethanolamine transferase modifying lipid A in Gram‐negative bacteria. MCR‐3 generally mediates low‐level (≤8 mg L−1) colistin resistance among Enterobacteriaceae, but occasionally confers high‐level (>128 mg L−1) resistance in aeromonads. Herein, it is determined that MCR‐3, together with another lipid A modification mediated by the arnBCADTEF operon, may be responsible for high‐level colistin resistance in aeromonads. Lipid A is the critical site of pathogens for Toll‐like receptor 4 recognizing. However, it is unknown whether or how MCR‐3‐mediated lipid A modification affects the host immune response. Compared with the wild‐type strains, increased mortality is observed in mice intraperitoneally‐infected with mcr‐3‐positive Aeromonas salmonicida and Escherichia coli strains, along with sepsis symptoms. Further, mcr‐3‐positive strains show decreased clearance rates than wild‐type strains, leading to bacterial accumulation in organs. The increased mortality is tightly associated with the increased tissue hypoxia, injury, and post‐inflammation. MCR‐3 expression also impairs phagocytosis efficiency both in vivo and in vitro, contributing to the increased persistence of mcr‐3‐positive bacteria in tissues compared with parental strains. This study, for the first time, reveals a dual function of MCR‐3 in bacterial resistance and pathogenicity, which calls for caution in treating the infections caused by mcr‐positive pathogens.

Organic–inorganic halide two-dimensional (2D) layered perovskites have been demonstrated to have better environmental stability than conventional three-dimensional perovskites. In this study, we investigate the fabrication of electron transport layer (ETL)-free Ruddlesden–Popper 2D perovskite solar cells (PSCs) by tuning the work function of a fluorine-doped tin oxide (FTO) electrode. With the deposition of polyethylenimine (PEIE) onto its surface, the work function of the FTO electrode could be raised from −4.72 to −4.08 eV, which is more suitable for electron extraction from the perovskite absorber. Using this technique, the ETL-free 2D PSCs exhibited an excellent power conversion efficiency (PCE) of 12.7% (on average), which is substantially higher than that of PSCs fabricated on a pristine FTO electrode (9.6%). Compared with the PSCs using TiO2, the ETL-free PSCs could be fabricated under a low processing temperature of 100 °C with excellent long-term stability. After 15 days, the FTO/PEIE-based ETL-free PSCs showed a PCE degradation of 16%, which is significantly lower than that of the TiO2-based case (29%). The best-performing PSC using a FTO/PEIE cathode showed a high PCE of 13.0%, with a small hysteresis degree of 2.3%.

There are various forms of clearance at the connection of various parts of the hydraulic support. However, the influence of clearance has been ignored in various related research studies of the hydraulic support. In order to clearly grasp the accurate impact contact response law between coal gangue and the hydraulic support, the radial clearance in the pin shaft connection structure of the tail beam is considered for the first time in this paper. By constructing the theoretical contact model of the pin shaft connection, the difficulty of studying the interaction between coal gangue and the hydraulic support through theoretical solution is proved. On this basis, the finite element contact simulation analysis method is proposed to study the impact contact behavior between coal gangue and the tail beam. This paper constructed the finite element impacting simulation model between coal gangue and the radial clearance-contained tail beam structure and carried out impact contact simulation between coal gangue and the multiple clearance-contained tail beam structure as well as the changing clearance-contained tail beam structure, respectively, and contact responses of the tail beam structure such as the spring stress, the pin shaft test point stress, acceleration, and velocity of the tail beam test point under different working conditions are obtained. The influence law of clearance on different contact responses is studied, and the differences of contact responses after coal gangue impact between two clearance-contained tail beam structures and three clearance-contained tail beam structures are compared and analyzed. Research results show that, in the condition of multiclearance, the amplitude of each contact response when gangue is impacted is greater than that of coal. When the radial clearance of the connection unit increases from 0 to 0.25 mm, the overall fluctuation amplitude of the contact responses decreases. In 3-clearance state, increase of the radial clearance size of the connection unit will lead to the increase of the spring stress, the stress of the pin shaft test point, and the velocity of the tail beam test point gradually and the decrease of the acceleration of the tail beam test point. Throughout the research, the vibration response of the pin shaft can be taken as coal gangue recognition parameter. The work provides a theoretical basis for the study of the influence law of clearance on hydraulic support and provides a reference for the study of contact behavior between coal gangue and the hydraulic support.

While carbapenem use is prohibited in the poultry production chain and carbapenem-resistant Enterobacteriaceae (CRE) are absent from hatchery farms, New Delhi metallo-β-lactamase-producing CRE contamination of commercial broiler chicken farms (grow-out farms) can occur via living hosts such as flies. However, it is not known whether the inanimate factors from in-house environment play a role in the persistence of CRE on commercial farms. Herein, we monitored one typical broiler house in Hebei Province, China, from January 2017 to April 2018. We collected 350 cloacal samples from four broiler batches along with 582 environmental samples (194 in the raising period and 388 in the vacancy period) from sites including the surfaces of drooping boards, feeding troughs, nipple drinkers, corridor floors, sewage trenches, and air. All samples were screened for blaNDM and cultured for NDM-producing isolates. The resistance profiles, genotypes, and genetic context of blaNDM in CRE isolates were further characterized. Results showed that 1-day-old broilers, which were transferred from a hatchery farm and negative for CRE, acquired blaNDM within 24 h of transfer (2 days of age), with a detection rate of up to 18.6%. High blaNDM detection rates (26.8%–31.4%) were obtained among all environmental samples except air after standard cleaning and disinfection during the vacancy period. blaNDM carriage rates (52.9%–72.9%) within the flocks remain stable and high across the next three broiler batches. Overall, 279 NDM-producing bacteria, including 259 Enterobacteriaceae (8 species), 14 Morganellaceae (3 species), three Alcaligenes faecalis and three Pseudomonas putida isolates, were recovered from 85 (24.3%) cloacal and 101 (17.4%) environmental samples. Three NDM variants, including NDM-5 (n = 181), NDM-1 (n = 92), and NDM-9 (n = 3), and a novel NDM-like-metallo-β-lactamase (NLM, n = 3) were identified among the samples. The predominant NDM-producing CRE species among the samples were Klebsiella pneumoniae (CRKP; 32.6%, n = 91) and Escherichia coli (CREC; 27.2%, n = 76). Both clonal and horizontal transmission of blaNDM and an overlap of sequence types (STs) were observed in both CREC and CRKP from chicken and environmental samples. Notably, ST6751 CREC and ST37 CRKP persisted throughout the 16-month surveillance period. IncX3 (n = 197, 7 species), IncA/C2 (n = 41, 5 species), and IncFII (n = 8, E. coli) were the three major blaNDM-carrying plasmid types among the isolates. Although routine cleaning and disinfection procedures and “all-in/all-out” management were performed, once introduced to the farm environment, a diverse range of NDM-positive isolates may survive and persist, becoming an important reservoir of NDM-positive CRE for broiler chickens. Therefore, cleaning and disinfection procedures should be improved on poultry farms to avoid cross-contamination of NDM-producing bacteria between different batches of chickens, as well as further downstream in the poultry production chain.

Conical pick wear is an urgent problem in the roadway excavation caused by hard rock difficult to break. The traditional method of increasing cutting power to improve cutting performance of conical pick significantly increases pick wear. In the paper, a saw blade and conical pick combined cutting method is proposed based on increased free surface. To research the fracture morphology and cutting force of rock plate, theoretical, numerical, and experimental methods are used. By theoretical research, the bending mechanical model of rock plate bending is established. The cutting position and the junction between the free sides and fixed sides are preferentially broken. A numerical model combining the erosion and damage constitutive model is built, and the cutting process of rock plate was presented. According to rock plate experiment, the peak cutting force increases with the increasing uniaxial compressive strength, thickness of rock plate, and cutting depth of conical pick and decreases with the increasing width and height of rock plate. Exponential relationships exist between peak cutting force and thickness, width and height of rock plate, and cutting depth of conical pick. Linear relationship exists between peak cutting force and uniaxial compressive strength. The size of rock fragments increases with uniaxial compressive strength, width, and height of rock plate.

We investigated antimicrobial resistance trends and characteristics of ESBL-producing Escherichia coli isolates from pets and whether this correlates with antibiotic usage in the clinic. Clinical samples containing E. coli from diseased cats and dogs were screened for antibiotic sensitivity and associated genotypic features. We identified 127 E. coli isolates from 1886 samples from dogs (n = 1565) and cats (n = 321) with the majority from urinary tract infections (n = 108, 85%). High rates of resistance were observed for β-lactams and fluoroquinolones and resistance to > 3 antibiotic classes (MDR) increased from 67% in 2012 to 75% in 2017 (P < 0.0001). This was especially true for strains resistant to 6–9 antibiotics that increased from 26.67 to 60.71%. Increased rates in β-lactam use for clinical treatment accompanied these increasing resistance rates. Accordingly, the most frequently encountered subtypes were blaCTX–M (n = 44, 34.65%), blaCTX–M–65 (n = 19) and blaCTX–M–15 (n = 18) and qnrB (n = 119, 93.70%). The blaCTX–M-isolates possessed 36 unique pulsed field electrophoretic types (PFGEs) and 28 different sequence types (STs) in ST405 (7, 15.9%), ST131 (3, 6.8%), ST73, ST101, ST372, and ST827 (2, 4.5% each) were the most prevalent. This data demonstrated a high level of diversity for the blaCTX–M-positive E. coli isolates. Additionally, blaNDM–5 was detected in three isolates (n = 3, 2.36%), comprised of two ST101 and one ST405 isolates, and mcr-1 was also observed in three colistin-resistant E. coli with three different STs (ST6316, ST405, and ST46). Our study demonstrates an increasing trend in MDR and ESBL-producing E. coli and this correlated with β-lactam antibiotic usage for treatment of these animals. This data indicates that there is significant risk for the spread of resistant bacteria from pets to humans and antibiotic use for pets should be more strictly regulated.

Carbapenem-resistant pathogens mediated by metallo-beta-lactamases (MBLs) have spread worldwide, where NDM-1 is a typical and key MBL. Here, we firstly discussed the distribution characterization of NDM-1, which produces multidrug-resistant Proteus mirabilis among broilers in China. From January to April 2019, 40 (18.1%, 40/221) blaNDM-1-carrying P. mirabilis strains were recovered from commercial broilers in slaughterhouse B in China. All the isolates were resistant to imipenem, meropenem and other β-lactams. These isolates belong to five clusters identified via pulsed field gel electrophoresis (PFGE). Further studies on twenty representative strains revealed that seven blaNDM-1 genes were located on plasmids with sizes of 104.5–138.9 kb. Notably, only three strains (PB72, PB96 and PB109) were successfully transferred to Escherichia coli J53, while the other four isolates were located in nontransferable plasmids. The rest were harbored in chromosomes. Ulteriorly, based on whole genome sequencing (WGS), these twenty isolates showed four typical phylogenetic clades according to single nucleotide polymorphisms (SNPs) of a core genome and presented four main genomic backbone profiles, in which type II/III strains shared a similar genetic context. All of the above is evidence of blaNDM-1 transmission and evolution in P. mirabilis, suggesting that the prevalence may be more diverse in broiler farms. Accordingly, as intestinal and environmental symbiotic pathogens, blaNDM-1-positive P. mirabilis will pose greater threats to the environment and public health.

Since the first report of the plasmid-mediated, colistin-resistant gene, mcr-1, nine mcr genes and their subvariants have been identified. The spreading scope of mcr-1~10 varies greatly, suggesting that mcr-1~10 may have different evolutionary advantages. Depending on MCR family phylogeny, mcr-6 is highly similar to mcr-1 and -2, and mcr-7~10 are highly similar to mcr-3 and -4. We compared the expression effects of MCR-1~5 on bacteria of common physiological background. The MCR-1-expressing strain showed better growth than did MCR-2~5-expressing strains in the presence of colistin. LIVE/DEAD staining analysis revealed that MCR-3~5 expression exerted more severe fitness burdens on bacteria than did MCR-1 and -2. Bacteria expressing MCRs except MCR-2 showed enhanced virulence with increased epithelial penetration ability determined by trans-well model (p < 0.05). Enhanced virulence was also observed in the Galleria mellonella model, which may have resulted from bacterial membrane damage and different levels of lipopolysaccharide (LPS) release due to MCR expression. Collectively, MCR-1-expressing strain showed the best survival advantage of MCR-1~5-expressing strains, which may partly explain the worldwide distribution of mcr-1. Our results suggested that MCR expression may cause increased bacterial virulence, which is alarming, and further attention will be needed to focus on the control of infectious diseases caused by mcr-carrying pathogens.

Abstract Background In structure-based drug design, binding affinity prediction remains as a challenging goal for current scoring functions. Development of target-biased scoring functions provides a new possibility for tackling this problem, but this approach is also associated with certain technical difficulties. We previously reported the Knowledge-Guided Scoring (KGS) method as an alternative approach (BMC Bioinformatics, 2010, 11, 193–208). The key idea is to compute the binding affinity of a given protein-ligand complex based on the known binding data of an appropriate reference complex, so the error in binding affinity prediction can be reduced effectively. Results In this study, we have developed an upgraded version, i.e. KGS2, by employing 3D protein-ligand interaction fingerprints in reference selection. KGS2 was evaluated in combination with four scoring functions (X-Score, ChemPLP, ASP, and GoldScore) on five drug targets (HIV-1 protease, carbonic anhydrase 2, beta-secretase 1, beta-trypsin, and checkpoint kinase 1). In the in situ scoring test, considerable improvements were observed in most cases after application of KGS2. Besides, the performance of KGS2 was always better than KGS in all cases. In the more challenging molecular docking test, application of KGS2 also led to improved structure-activity relationship in some cases. Conclusions KGS2 can be applied as a convenient “add-on” to current scoring functions without the need to re-engineer them, and its application is not limited to certain target proteins as customized scoring functions. As an interpolation method, its accuracy in principle can be improved further with the increasing knowledge of protein-ligand complex structures and binding affinity data. We expect that KGS2 will become a practical tool for enhancing the performance of current scoring functions in binding affinity prediction. The KGS2 software is available upon contacting the authors.

A closed-loop dispersion measurement framework (CLDM) is proposed. Carrying out dispersion compensation with an arbitrary trial dispersion on the interferogram under test, and using a criterion function as feedback to adjust the trial dispersion until the optimum is reached the trial dispersion is the measured result. The CLDM framework is not only noise-robust but can also cope with the case of multiple peaks that provides high resolution. We use it to measure the distributed birefringence dispersion (BD) chromatic dispersion difference of the two polarized modes of polarization maintaining fibers (PMFs). In this regime, the optimum of dispersion compensation is that the signal energy of every peak in the interferogram is concentrated. Thus, we present a criterion function to evaluate the signal energy concentration. Theoretical and experimental demonstration of this method is implemented. In addition, the spatial resolution (-4 ps/nm/km and 2 × 10-4 ps/nm2/km, respectively.

Lead(II)-acetate (Pb(Ac)2) is a promising lead source for the preparation of organolead trihalide perovskite materials, which avoids the use of inconvenient anti-solvent treatment. In this study, we investigated the effect of cesium doping on the performance of Pb(Ac)2-based perovskite solar cells (PSCs). We demonstrate that the quality of the CH3NH3PbI3 perovskite film was improved with increased crystallinity and reduced pinholes by doping the perovskite with 5 mol% cesium. As a result, the power conversion efficiency (PCE) of the PSCs was improved from 14.1% to 15.57% (on average), which was mainly induced by the significant enhancements in short-circuit current density and fill factor. A PCE of 18.02% was achieved for the champion device of cesium-doped Pb(Ac)2-based PSCs with negligible hysteresis and a stable output. Our results indicate that cesium doping is an effective approach for improving the performance of Pb(Ac)2-based PSCs.

The poor loading performance of shearer drums restricts the development and production efficiency of coal in thin coal seams. Changing operation and structural parameters can improve the drum’s loading performance to some extent, but the effect is not obvious. A two-segment differential rotational speed drum (TDRSD) was proposed after analyzing the drum’s influence mechanism on coal particles. To further reveal the drum’s coal loading principle, the velocity, particles distribution, and loading rate were analyzed. The effect of the matching relationship of the rotational speed and helix angle between the front and rear drum are also discussed. The results show that a lower front drum rotational speed had a positive impact on improving the loading performance, and the loading rate first increases and then decreases with the increase in rear drum rotational speed. The optimal loading performance was obtained in the range 60–67.5 rpm. The front drum’s helix angle had no evident effect on loading performance, and the loading rate increase with the increase in the rear drum’s helix angle. The results provide a reference and guidance for operation parameters selection, structure design, and drum optimization.

The spread of carbapenem-resistant Enterobacteriaceae (CRE) mediated by New Delhi metallo-β-lactamase (NDM) poses a serious challenge to clinicians and has become a major public health concern. NDM has been evolving into variants that possess different hydrolysis activity toward antibiotics, so as to affect treatment strategy. In addition, very few studies on NDM variants have focused on animal-derived bacterial isolates. Our study reports a novel NDM variant, NDM-20, in an isolate of Escherichia coli CCD1 recovered from the food animal swine in China. The isolate that was assigned to ST1114, exhibited high level resistance to all β-lactams tested, including aztreonam and carbapenems. The gene of blaNDM-20 was located on an IncX3-type plasmid, surrounded by multiple insertion sequences. Sequencing analysis demonstrated that blaNDM-20 contained three point mutations at positions 262 (G→T), 460 (A→C), and 809 (G→A), compared with blaNDM-1, and just one point mutation at position 809 (G→A), relative to blaNDM-5. Functional analysis revealed that the blaNDM-20 transformant, DH5α+pHSG398/NDM-20, exhibited a higher resistance to ertapenem than that of blaNDM-1 transformant DH5α+pHSG398/NDM-1. Kinetic parameter analysis showed that NDM-20 had increased enzymatic activity against some penicillins and cephalosporins but decreased carbapenemase activity relative to NDM-5. The identification of NDM-20 further confirms the evolution and prevalence of NDM variants in bacteria of food-animal origin.

In this work, we used acetic acid as an additive for the preparation of ZnO layers and improved the performance of poly{4,8-bis[(2-ethylhexyl)-oxy]benzo[1,2-b:4,5-b’] dithiophene-2,6-diyl-alt-3-fluoro-2-[(2-ethylhexyl)carbonyl]thieno[3,4-b]thiophene- 4,6-diyl} (PTB7)-based inverted organic solar cells. The addition of acetic acid to the ZnO precursor solution improved the transparency and conductivity of the sol-gel-synthesized ZnO film, by increasing the grain size of the film. Accordingly, the power conversion efficiency (PCE) of the organic solar cells was improved from 6.42% to 7.55%, which was mainly caused by the enhanced current density and fill factor. The best sample demonstrated a high PCE of 7.85% with negligible hysteresis and good stability. Our results indicate that using acetic acid as an additive for the preparation of ZnO is a simple and effective way of fabricating high-performance inverted organic solar cells.

ABSTRACT The mobile colistin resistance gene mcr-1 has attracted global attention, as it heralds the breach of polymyxins, one of the last-resort antibiotics for the treatment of severe clinical infections caused by multidrug-resistant Gram-negative bacteria. To date, six slightly different variants of mcr-1, and a second mobile colistin resistance gene, mcr-2, have been reported or annotated in the GenBank database. Here, we characterized a third mobile colistin resistance gene, mcr-3. The gene coexisted with 18 additional resistance determinants in the 261-kb IncHI2-type plasmid pWJ1 from porcine Escherichia coli. mcr-3 showed 45.0% and 47.0% nucleotide sequence identity to mcr-1 and mcr-2, respectively, while the deduced amino acid sequence of MCR-3 showed 99.8 to 100% and 75.6 to 94.8% identity to phosphoethanolamine transferases found in other Enterobacteriaceae species and in 10 Aeromonas species, respectively. pWJ1 was mobilized to an E. coli recipient by conjugation and contained a plasmid backbone similar to those of other mcr-1-carrying plasmids, such as pHNSHP45-2 from the original mcr-1-harboring E. coli strain. Moreover, a truncated transposon element, TnAs2, which was characterized only in Aeromonas salmonicida, was located upstream of mcr-3 in pWJ1. This ΔTnAs2-mcr-3 element was also identified in a shotgun genome sequence of a porcine E. coli isolate from Malaysia, a human Klebsiella pneumoniae isolate from Thailand, and a human Salmonella enterica serovar Typhimurium isolate from the United States. These results suggest the likelihood of a wide dissemination of the novel mobile colistin resistance gene mcr-3 among Enterobacteriaceae and aeromonads; the latter may act as a potential reservoir for mcr-3. IMPORTANCE The emergence of the plasmid-mediated colistin resistance gene mcr-1 has attracted substantial attention worldwide. Here, we examined a colistin-resistant Escherichia coli isolate that was negative for both mcr-1 and mcr-2 and discovered a novel mobile colistin resistance gene, mcr-3. The amino acid sequence of MCR-3 aligned closely with phosphoethanolamine transferases from Enterobacteriaceae and Aeromonas species originating from both clinical infections and environmental samples collected in 12 countries on four continents. Due to the ubiquitous profile of aeromonads in the environment and the potential transfer of mcr-3 between Enterobacteriaceae and Aeromonas species, the wide spread of mcr-3 may be largely underestimated. As colistin has been and still is widely used in veterinary medicine and used at increasing frequencies in human medicine, the continuous monitoring of mobile colistin resistance determinants in colistin-resistant Gram-negative bacteria is imperative for understanding and tackling the dissemination of mcr genes in both the agricultural and health care sectors.

The New Delhi metallo-β-lactamase-1 (NDM-1) is a typical carbapenemase and plays a crucial role in antibiotic-resistance bacterial infection. Phylogenetic analysis, performed on known NDM-variants, classified NDM enzymes in seven clusters. Three of them include a major number of NDM-variants. In this study, we evaluated the role of the V88L substitution in NDM-24 by kinetical and structural analysis. Functional results showed that V88L did not significantly increase the resistance level in the NDM-24 transformant toward penicillins, cephalosporins, meropenem, and imipenem. Concerning ertapenem, E. coli DH5α/NDM-24 showed a MIC value 4-fold higher than that of E. coli DH5α/NDM-1. The determination of the kcat, Km, and kcat/Km values for NDM-24, compared with NDM-1 and NDM-5, demonstrated an increase of the substrate hydrolysis compared to all the β-lactams tested, except penicillins. The thermostability testing revealed that V88L generated a destabilized effect on NDM-24. The V88L substitution occurred in the β-strand and low β-sheet content in the secondary structure, as evidenced by the CD analysis data. In conclusion, the V88L substitution increases the enzyme activity and decreases the protein stability. This study characterizes the role of the V88L substitution in NDM-24 and provides insight about the NDM variants evolution.

The local electronic states around a single As (Te, Se) vacancy are investigated in order to shed light on the role of ligands in a series of iron-based superconductors. Such a vacancy can produce a local hopping correction ranging from −0.22 to 0.12 eV and always induce two in-gap resonance peaks in the local density of states (LDOS) at the fixed symmetrical bias voltages, which are rather robust and irrelevant to the phase of superconducting order parameter. The LDOS images near the defect predominantly possess 0° and 45° stripes. These energy-dependent charge modulations created by quasiparticle interference are originated in the nesting effect between the inner (outer) hole Fermi surface around Γ point and the inner (outer) electron Fermi surface around M point.

By combining a polymer-clad optic fiber and a vitreous-clad optic fiber, we proposed and fabricated a novel optic fiber surface plasmon resonance (SPR) sensor to conduct two-channel sensing at the same detection area. The traditional optic fiber SPR sensor has many disadvantages; for example, removing the cladding requires corrosion, operating it is dangerous, adjusting the dynamic response range is hard, and producing different resonance wavelengths in the sensing area to realize a multi-channel measurement is difficult. Therefore, in this paper, we skillfully used bare fiber grinding technology and reverse symmetry welding technology to remove the cladding in a multi-mode fiber and expose the evanescent field. On the basis of investigating the effect of the grinding angle on the dynamic range change of the SPR resonance valley wavelength and sensitivity, we combined polymer-clad fiber and vitreous-clad fiber by a smart design structure to realize at a single point a two-channel measurement fiber SPR sensor. In this paper, we obtained a beautiful spectral curve from a multi-mode fiber two-channel SPR sensor. In the detection range of the refractive rate between 1.333 RIU and 1.385 RIU, the resonance valley wavelength of channel Ⅰ shifted from 622 nm to 724 nm with a mean average sensitivity of 1961 nm/RIU and the resonance valley wavelength of channel Ⅱ shifted from 741 nm to 976 nm with a mean average sensitivity of 4519 nm/RIU.