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Abstract The Traveling Salesman Problem (TSP) is a classic problem in combinatorial optimization, aiming to find the shortest path that traverses all cities and eventually returns to the starting point. The ant colony optimization algorithm has achieved significant results, but when the number of cities increases, the ant colony algorithm is prone to fall into local optimal solutions, making it difficult to obtain the global optimal path. To overcome this limitation, this paper proposes an innovative hybrid ant colony algorithm. Our main motivation is to introduce other optimization strategies to improve the global search ability and convergence speed of the ant colony algorithm in solving TSP problems. We first incorporate the iterative solution of the sparrow search algorithm (SSA) into the ant colony algorithm to provide a better initial pheromone distribution. Second, we improve the pheromone update method to enhance the algorithm’s diversity during the search process and reduce the risk of falling into local optima. Finally, we define a dynamic pheromone evaporation factor to adjust the pheromone evaporation rate according to real-time changes in the search process. Through simulation tests on large-scale TSP problems and practical applications, we find that the hybrid ant colony algorithm outperforms the ant colony algorithm in both accuracy and running time. In Eg.2, the average accuracy of ISSA-ACO is improved by 12%, and the average running time is reduced by 45.6%. This study not only provides a new and effective method for solving large-scale TSP problems but also provides valuable references and insights for the application of ant colony algorithms in solving other complex optimization problems. At the same time, our research further verifies the effectiveness of improving heuristic algorithms by fusing different optimization strategies, providing new ideas and directions for future algorithm design and optimization.

Infections caused by intracellular bacterial pathogens are difficult to treat since most antibiotics have low cell permeability and undergo rapid degradation within cells. The rapid development and dissemination of antimicrobial–resistant strains have exacerbated this dilemma. With the increasing knowledge of host–pathogen interactions, especially bacterial strategies for survival and proliferation within host cells, host-directed therapy (HDT) has attracted increased interest and has emerged as a promising anti-infection method for treating intracellular infection. Herein, we applied a cell-based screening approach to a US Food and Drug Administration (FDA)-approved drug library to identify compounds that can inhibit the intracellular replication of Salmonella Typhimurium (S. Typhimurium). This screening allowed us to identify the antidiarrheal agent loperamide (LPD) as a potent inhibitor of S. Typhimurium intracellular proliferation. LPD treatment of infected cells markedly promoted the host autophagic response and lysosomal activity. A mechanistic study revealed that the increase in host autophagy and elimination of intracellular bacteria were dependent on the high expression of glycoprotein nonmetastatic melanoma protein B (GPNMB) induced by LPD. In addition, LPD treatment effectively protected against S. Typhimurium infection in Galleria mellonella and mouse models. Thus, our study suggested that LPD may be useful for the treatment of diseases caused by intracellular bacterial pathogens. Moreover, LPD may serve as a promising lead compound for the development of anti-infection drugs based on the HDT strategy.

The overuse of antibiotics has caused the emergence of antibiotic-resistant strains, such as multidrug-resistant, extensively drug-resistant, and pandrug-resistant bacteria. The treatment of infections caused by such strains has become a formidable challenge. In the post-antibiotic era, phage therapy is an attractive solution for this problem and some successful phase 1 and 2 studies have demonstrated the efficacy and safety of phage therapy over the last decade. It is a form of evolutionary medicine, phages exhibit immunomodulatory and anti-inflammatory properties. However, phage therapy is limited by factors, such as the narrow spectrum of host strains, the special pharmacokinetics and pharmacodynamics in vivo, immune responses, and the development of phage resistance. The aim of this minireview was to compare the potencies of lytic phages and chemical antibiotics to treat bacterial infections. The advantages of phage therapy has fewer side effects, self-replication, evolution, bacterial biofilms eradication, immunomodulatory and anti-inflammatory properties compared with chemical antibiotics. Meanwhile, the disadvantages of phage therapy include the narrow spectrum of available host strains, the special pharmacokinetics and pharmacodynamics in vivo, immune responses, and phage resistance hurdles. Recently, some researchers continue to make efforts to overcome these limitations of phage therapy. Phage therapy will be a welcome addition to the gamut of options available for treating antibiotic-resistant bacterial infections. We focus on the advantages and limitations of phage therapy with the intention of exploiting the advantages and overcoming the limitations.

Introduction It is encouraged to estimate the effectiveness of components within the enhanced recovery after surgery (ERAS) protocol through patient-reported outcomes, alongside doctor-reported outcomes and length of hospital stay. At present, studies on the contributions of optimal anaesthetic drugs within the ERAS protocol to patient-reported and doctor-reported outcomes are limited. Therefore, this study aims to pragmatically evaluate the effectiveness and safety of general anaesthesia (GA) with remimazolam tosilate within the ERAS protocol on intraoperative haemodynamics and postoperative recovery in adults undergoing elective surgeries, compared with propofol.Methods and analysis This study is a single-centre, randomised, blinded, positive-controlled, pragmatic clinical trial. A total of 900 patients, aged ≥18 years old, scheduled for an elective surgical procedure under GA will be included. Patients will be randomised in a 1:1 ratio to the remimazolam group (the GA with remimazolam tosilate within the ERAS protocol group) or propofol group (the GA with propofol within the ERAS protocol group), stratified by general surgery, thoracic surgery and other surgeries (including urological surgery and otolaryngology surgery). The primary outcomes include the 24-hour postoperative quality of recovery-40 score and the rate of intraoperative hypotension. Secondary endpoints include the rate of sedative hypotension requiring treatment, the haemodynamic profiles, the 72-hour postoperative quality of recovery-40 score, the functional anaesthetic capability, adverse events and complications, quality of life within 3 months as well as economic health outcomes.Ethics and dissemination This study protocol has been approved by the ethics committee of Guangdong Provincial People’s Hospital (KY-H-2022-005-03-08). Dissemination plans will be presented at scientific meetings and in scientific publications.Trial registration number ChiCTR2200062520

ABSTRACT Salmonella enterica is an important zoonotic intracellular bacterial pathogen that is capable of causing infections ranging from localized gastroenteritis to fatal systemic infection in humans and food-producing animals. The increasing antibiotic resistance in Salmonella isolates, especially the emergence of MDR and newer XDR strains, has compromised the efficacy of conventional antimicrobial therapy for Salmonella infections. Hence, it is desirable to develop alternative therapeutic means to tackle the antimicrobial resistance crisis. In this study, we screened plant-derived compounds to identify inhibitors of Salmonella invasion of host cells. These efforts identified fisetin as a possible protector against infection. Further mechanistic studies revealed that fisetin suppressed the function of type III secretion system 1 (T3SS-1), the virulence determinant critical for Salmonella invasion. Fisetin appears to interfere with the interaction between HilD and its relevant promoters, thereby decreasing the transcription of hilA, the central transcriptional regulator that functions to activate the expression of T3SS-1 effector proteins and structural elements. In addition, administration of fisetin in the Salmonella murine infection model resulted in reduced bacterial colonization, alleviation of histopathological destruction, and decreased proinflammatory cytokine levels. Taken together, our study establishes that the natural compound fisetin can be used as a lead compound for the development of anti-Salmonella drugs targeting T3SS-1. IMPORTANCE Salmonella spp. remains a major worldwide health concern that causes significant morbidity and mortality in both humans and animals. The spread of antimicrobial resistant strains has declined the efficacy of conventional chemotherapy. Thus, novel anti-infection drugs or strategies are needed. Anti-virulence strategy represents one of the promising means for the treatment of bacterial infections. In this study, we found that the natural compound fisetin could inhibit Salmonella invasion of host cells by targeting SPI-1 regulation. Fisetin treatment impaired the interaction of the regulatory protein HilD with the promoters of its target genes, thereby suppressing the expression of T3SS-1 effectors as well as structural proteins. Moreover, fisetin treatment could reduce pathology in the Salmonella murine infection model. Collectively, our results suggest that fisetin may serve as a promising lead compound for the development of anti-Salmonella drugs.

ABSTRACTResistance of bacteria to antibiotics is a major concern in medicine and veterinary science. The bacterial biofilm structures not only prevent the penetration of drugs into cells within the biofilm’s interior but also aid in evasion of the host immune system. Hence, there is an urgent need to develop novel therapeutic approaches against bacterial biofilms. One potential strategy to counter biofilms is to use phage depolymerases that degrade the matrix structure of the bacteria and enable access to bacterial cells. This review mainly discusses the methods by which phage depolymerases enhance the efficacy of the human immune system and the therapeutic applications of some phage depolymerases, such as single phage depolymerase application, combined therapy with phage depolymerase and antibiotics, and phage depolymerase cocktails, for treating bacterial biofilms. This review also summarizes the relationship between bacterial biofilms and antibiotic resistance.

ABSTRACT Hypervirulent Klebsiella pneumoniae with capsular polysaccharides (CPSs) causes severe nosocomial- and community-acquired infections. Phage-derived depolymerases can degrade CPSs from K. pneumoniae to attenuate bacterial virulence, but their antimicrobial mechanisms and clinical potential are not well understood. In the present study, Klebsiella phage GH-K3-derived depolymerase Depo32 (encoded by gene gp32) was identified to exhibit high efficiency in specifically degrading the CPSs of K2 serotype K. pneumoniae. The cryo-electron microscopy structure of trimeric Depo32 at a resolution up to 2.32 Å revealed potential catalytic centers in the cleft of each of the two adjacent subunits. K. pneumoniae subjected to Depo32 became more sensitive to phagocytosis by RAW264.7 cells and activated the cells by the mitogen-activated protein kinase signaling pathway. In addition, intranasal inoculation with Depo32 (a single dose of 200 µg, 20 µg daily for 3 days, or in combination with gentamicin) rescued all C57BL/6J mice infected with a lethal dose of K. pneumoniae K7 without interference from its neutralizing antibody. In summary, this work elaborates on the mechanism by which Depo32 targets the degradation of K2 serotype CPSs and its potential as an antivirulence agent. IMPORTANCE Depolymerases specific to more than 20 serotypes of Klebsiella spp. have been identified, but most studies only evaluated the single-dose treatment of depolymerases with relatively simple clinical evaluation indices and did not reveal the anti-infection mechanism of these depolymerases in depth. On the basis of determining the biological characteristics, the structure of Depo32 was analyzed by cryo-electron microscopy, and the potential active center was further identified. In addition, the effects of Depo32 on macrophage phagocytosis, signaling pathway activation, and serum killing were revealed, and the efficacy of the depolymerase (single treatment, multiple treatments, or in combination with gentamicin) against acute pneumonia caused by Klebsiella pneumoniae was evaluated. Moreover, the roles of the active sites of Depo32 were also elucidated in the in vitro and in vivo studies. Therefore, through structural biology, cell biology, and in vivo experiments, this study demonstrated the mechanism by which Depo32 targets K2 serotype K. pneumoniae infection.

Abstract In order to solve the problem that the conventional tracker is not adapted to the abrupt motion, a tracking algorithm based on the improved salp swarm algorithm (ISSA) was proposed. Visual tracking is considered to be a process of locating the optimal position through the interaction between leaders and followers in successive images. Firstly, the adaptive mechanism of leader and follower is introduced into the original salp swarm algorithm (SSA) to balance the exploitation and exploration of the algorithm. This method can improve the accuracy and effect of tracking. Secondly, the golden‐sine algorithm was used to update the position of followers, considering that the SSA had a single spatial search mode for followers and was easy to fall into the local optimum. By comparing with 19 classical tracking algorithms, qualitative and quantitative analysis is carried out to verify the tracking effect of the proposed method. A large number of experimental results show that the algorithm proposed here has good performance in visual tracking, especially for mutation motion tracking.

Abstract: The development of electronics and software has resulted in the ability of twin agents to act as digital counterparts for the optimization, control, and monitoring of real power grids. When increasing regulation resources are connected to the power grid, is challenging for independent system operators to use a centralized controller to achieve power tracking and balance. Therefore, the present study applied device-level-based digital twins to monitor physical signals for computer-aided design for power tracking. Moreover, a consensus control-based distributed power tracking system is proposed for the physical-model simulation of the power grid. A communication network was also designed for realistic signal exchange. The combination of the proposed distributed power tracking method and communication network can accelerate computational efficiency and protect the privacy of the regulation resources. Finally, the performance of the proposed distributed power tracking method is validated in a simulation system with 10 regulation resources.

Abstract The maximum delivery pressure and the maximum rotational speed determine the power density of axial piston pumps. However, increasing the speed beyond the limit always accompanies cavitation, leading to the decrease of the volumetric efficiency. The pressure loss in the suction duct is considered a significant reason for the cavitation. Therefore, this paper proposes a methodology to optimize the shape of the suction duct aiming at reducing the intensity of cavitation and increasing the speed limit. At first, a computational fluid dynamics (CFD) model based on the full cavitation model (FCM) is developed to simulate the fluid field of the axial piston pump and a test rig is set to validate the model. Then the topology optimization is conducted for obtaining the minimum pressure loss in the suction duct. Comparing the original suction duct with the optimized one in the simulation model, the pressure loss in the suction duct gets considerable reduction, which eases the cavitation intensity a lot. The simulation results prove that the speed limit can increase under several different inlet pressures.

ABSTRACT Mobile colistin resistance (mcr) genes mediated by plasmids have widely disseminated throughout the world. Recently, 10 mcr genes (mcr-1 to mcr-10) and a large number of variants have been identified in more than 60 countries. However, only a few instances of Enterobacter cloacae complex (ECC) bearing mcr-10 from animal origin have been reported globally. The aim of this study was to fill a knowledge gap in mcr-10-positive ECC of animal origin and analyze the potential transmission trend and different characteristics between human and companion animal isolates. The mcr-10 gene was identified on a self-transmissible plasmid in the human isolate and non-transmissible plasmids in other three animal strains. mcr-10 was adjacent to a XerC-type tyrosine recombinase-gene, and various insertion sequences were located on the downstream of core conservative structure xerC-mcr-10, thus indicating this region might be a candidate for insertions of mobile genetic elements and mcr-10 might be mobilized by IS-mediated mechanisms. Moreover, phylogenetic analysis found that mcr-10-positive isolates were mainly distributed in the clade of Enterobacter roggenkampii, exhibiting significant species specificity. These findings indicated that mcr-10 has emerged among Enterobacter spp. within humans and companion animals, highlighting that the importance of taking effective control measures to monitor the dissemination and evolution of mcr genes. IMPORTANCE Colistin was considered as the last-resort drug against severe clinical infections caused by multidrug-resistant Gram-negative pathogens. Mobile colistin resistance (mcr) genes and its variants carried by plasmids have been reported in diverse niches in recent years, and yet few studies reported carriage of mcr-10 in ECC strains of companion animal origin. How plasmid-borne mcr-10 transmitted in opportunistic pathogens and different characteristics of mcr-10-bearing strains isolated from humans and companion animals are not well understood. In this study, we discovered mcr-10-harboring strains in multidrug-resistant ECC isolates of companion animal origin for the first time and conducted a comprehensive analysis of the genetic environment of mcr-10 from multiple countries around the world, providing the potential basis for formulating control measures to slow down the spread of colistin resistance.

Background: Oral microbiota reported to be associated with pancreatic diseases, including pancreatic cancer. However, the association of oral microbiome and pancreatic cancer has not been reviewed systematically. Objectives: To systematically investigate the association between the oral microbiome and pancreatic cancer risk. Design: A systematic review and meta-analysis. Data Sources and Methods: Systemic searches were conducted using PubMed, Medline, Cochrane Library, and Embase databases without any language restriction from conception to August 29, 2020. The studies that evaluated the association of oral microbiome and pancreatic cancer risk were included in this meta-analysis. Results: The six included studies encompassed a total of 863 pancreatic cancer cases and 906 controls. Four studies reported the overall oral microbiome in pancreatic cancer cases. A total of 12–17 species/clusters were correlated with pancreatic cancer. Three studies reported the odds ratios (ORs) or relative abundance of several oral microbiomes pieces/clusters, and the majority were associated with pancreatic cancer. Conclusions: Overall, this study supports the hypothesis of associations of variations of patients’ oral microbiota to pancreatic cancer. Nonetheless, due to all included studies were conducted in USA or Europe, additional original studies and meta-analysis particular studies from other countries are essential for an in-depth investigation into the role of oral bacteria in pancreatic cancer.

Energy cooperation is the forerunner and main engine of the Belt and Road Initiative. In the past ten years, hundreds of oil and gas cooperation projects have been operated in the countries along the Belt and Road and other countries by Chinese petroleum companies, with fruitful results achieved. The technical service and engineering construction is an important part of the cooperation. As the most important content for construction of oil and gas pipeline, hydrostatic testing is a most common method for verification of pipeline integrity. Based on the design experience of gathering pipelines in the oil and gas fields of the cooperation projects in Middle East and Africa, the 13 hydrostatic testing standards of the international organizations and petroleum corporations such as ASME, API, ISO, BSI, IPS, Saudi Aramco, ADNOC, Shell, Total and BP were sorted out, and the requirements for the test pressure and pressure holding time of the water quality test, strength test and tightness test were compared and analyzed. The research results are expected to provide reference for the design and construction of gathering pipelines in oversea oil and gas fields.

Citrobacter braakii is an opportunistic pathogen that induces aquatic infections in fish and turtles. In this study, a bacteriophage that infects C. braakii, named vB_CbrM_HP1, was isolated from sewage. This phage belongs to Myoviridae family, Ounavirinae subfamily, Mooglevirus genus. We also used the phage to treat crucian carp infection caused by C. braakii for the first time. vB_CbrM_HP1 was relatively stable at temperatures ranging from 4 to 60°C and pH values ranging from 3 to 11 but float slightly. When the multiplicities of infection (MOI) was 0.0001, the titer reached a maximum of 4.20 × 1010 PFU/ml. As revealed from the results of whole genomic sequence analysis, the total length of vB_CbrM_HP1 was 89335 bp, encoding 135 ORFs, 9 of which were

Salmonella enterica serovar Typhimurium (S. Typhimurium) is a zoonotic pathogen that can cause food poisoning and diarrhea in both humans and animals worldwide. The Salmonella pathogenicity island (SPI) genes encoded type III secretion system (T3SS) is important for S. Typhimurium invasion and replication in host cells. Due to the increasing problem of antibiotic resistance, antibiotic treatment for clinical Salmonella infection has gradually been limited. Anti-virulence inhibitors are a promising alternative to antibiotics because they do not easily induce bacterial antibiotic resistance. Here, we systematically evaluated the therapeutic effect of tannic acid (TA) on Salmonella-infected mice and elucidated its anti-infection mechanism. TA treatment improved the survival rate of S. Typhimurium-infected mice and alleviated cecum pathological lesions. In addition, TA inhibited S. Typhimurium invasion to HeLa cells without affecting their growth. Further studies showed that TA could inhibit the expression of sipA and sipB. This inhibition may be implemented by inhibiting the transcription of key regulatory and structural genes of the T3SS. This study provides an alternative anti-virulence strategy for Salmonella infection treatment.

Deep learning has brought revolutionary progress to computer vision, so intelligent inspection equipment based on computer vision has developed rapidly. However, due to the large number of existing deep features, it is difficult to deploy it on mobile devices to achieve real-time tracking speed. This paper presents a target-aware deep feature compression for power intelligent inspection tracking. First, a negative balance loss function is designed to mine channel features suitable for the current inspection scene by shrinking the contribution of pure background negative samples and enhancing the impact of difficult negative samples. Based on this, the deep feature compression model is combined with Siamese tracking framework to achieve real-time and robust tracking. Finally, we evaluate the proposed method on real application scenarios and general data to prove the practicability of the proposed method.

With the wide use of renewable energy sources and the requirement for energy storage technology, the field of power systems is facing the need for further technological innovation. This paper proposes a wide-area distributed energy model based on digital twins. This model was constructed to more fully optimize the coordination of wide-area distributed energy in order to rationally deploy and utilize new energy units. Moreover, the minimization of the power deviation between the dispatch command and the actual power regulation output was also taken into account. In contrast to previous dispatch research, the cooperative game co-optimization algorithm was applied to this model, enabling a distributed approach that can quickly obtain a high-quality power command scheduling scheme. Finally, the simulation and comparison experiments using this algorithm with the wide-area distributed energy (WDE) model showed that it had the advantages of significantly reducing the tracking error, average error, and total error and effectively improving the tracking accuracy. The proposed method can help reduce total power deviations by about 61.1%, 55.7%, 53.1%, and 74.8%.

Hydrogen (H2) energy is an ideal non-polluting renewable energy and can achieve long-term energy storage, which can effectively regulate the intermittence and seasonal fluctuation of solar energy. Solid oxide fuel cells (SOFC) can generate electricity from H2 with only outputs of water, waste heat, and almost no pollution. To solve the power generation instability and discontinuity of solar photovoltaic (PV) systems, a hybrid PV-SOFC power generation system has become one feasible solution. The “digital twin”, which integrates physical systems and information technology, offers a new view to deal with the current problems encountered during smart energy development. In particular, an accurate and reliable system model is the basis for achieving this vision. As core components, the reliable modelling of the PV cells and fuel cells (FCs) is crucial to the whole hybrid PV-SOFC power generation system’s optimal and reliable operation, which is based on the reliable identification of unknown model parameters. Hence, in this study, an artificial rabbits optimization (ARO)-based parameter identification strategy was proposed for the accurate modelling of PV cells and SOFCs, which was then validated on the PV double diode model (DDM) and SOFC electrochemical model under various operation scenarios. The simulation results demonstrated that ARO shows a more desirable performance in optimization accuracy and stability compared to other algorithms. For instance, the root mean square error (RMSE) obtained by ARO are 1.81% and 13.11% smaller than that obtained by ABC and WOA algorithms under the DDM of a PV cell. Meanwhile, for SOFC electrochemical model parameter identification under the 5 kW cell stack dataset, the RMSE obtained by ARO was only 2.72% and 4.88% to that of PSO for the (1 atm, 1173 K) and (3 atm, 1273 K) conditions, respectively. By establishing a digital twin model for PV cells and SOFCs, intelligent operation and management of both can be further achieved.

Background and Objectives: At present, the management of comminuted distal femur fractures remains challenging for orthopedic surgeons. The aim of this study is to report a surgical treatment for comminuted distal femur fractures using supplementary medial cortical bone plate allografts in conjunction with the lateral less invasive stabilization system (LISS) plates. Materials and Methods: From January 2009 to January 2014, the records of thirty-three patients who underwent supplementary medial cortical bone plate allografts combined with lateral LISS plates fixation were reviewed. Clinical and radiographic data were collected during regular postoperative follow-up visits. Functional outcomes were determined according to the special surgery knee rating scale (HSS) used at the hospital. Results: Thirty patients were followed for 13 to 73 months after surgery, with an average follow-up time of 31.3 months. The mean time to bone union was 5.4 months (range of 3–12 months) and the mean range of knee flexion was 105.6° (range of 80–130°). Of the remaining patients, 10 had a score of “Excellent”, while 10 had a score of “Good”. Three patients had superficial or deep infections, one patient had nonunion that required bone grafting, and one patient had post-traumatic knee arthritis. Conclusions: Based on these promising results, we propose that supplementary medial cortical bone plate allografts combined with lateral LISS plate fixation may be a good treatment option for comminuted distal femur fractures. This treatment choice not only resulted in markedly improved stability on the medial side of the femur, but also satisfactory outcomes for distal femoral fractures.

Trueperella pyogenes (T. pyogenes) is an important opportunistic animal pathogen that causes huge economic losses to the animal husbandry industry. The emergence of bacterial resistance and the unsatisfactory effect of the vaccine have prompted investigators to explore alternative strategies for controlling T. pyogenes infection. Due to the ability of phages to kill multidrug-resistant bacteria, the use of phage therapy to combat multidrug-resistant bacterial infections has attracted attention. In this study, a T. pyogenes phage, vB-ApyS-JF1 (JF1), was isolated from sewage samples, and its whole genome and biological characteristics were elucidated. Moreover, the protective effect of phage JF1 on a mouse bacteremic model caused by T. pyogenes was studied. JF1 harbors a double-stranded DNA genome with a length of 90,130 bp (30.57% G + C). The genome of JF1 lacked bacterial virulence–, antibiotic resistance– and lysogenesis-related genes. Moreover, the genome sequence of JF1 exhibited low coverage (

Rust of transmission line fittings is a major hidden risk to transmission safety. Since the fittings located at high altitude are inconvenient to detect and maintain, machine vision techniques have been introduced to realize the intelligent rust detection with the help of unmanned aerial vehicles (UAV). Due to the small size of fittings and disturbance of complex environmental background, however, there are often cases of missing detection and false detection. To improve the detection reliability and robustness, this paper proposes a new robust Faster R-CNN model with feature enhancement mechanism for the rust detection of transmission line fitting. Different from current methods that improve feature representation in front end, this paper adopts an idea of back-end feature enhancement. First, the residual network ResNet-101 is introduced as the backbone network to extract rich discriminative information from the UAV images. Second, a new feature enhancement mechanism is added after the region of interest (ROI) pooling layer. Through calculating the similarity between each region proposal and the others, the feature weights of the region proposals containing target object can be enhanced via the overlaying of the object’s representation. The weight of the disturbance terms can then be relatively reduced. Empirical evaluation is conducted on some real-world UAV monitoring images. The comparative results demonstrate the effectiveness of the proposed model in terms of detection precision and recall rate, with the average precision of rust detection 97.07%, indicating that the proposed method can provide an reliable and robust solution for the rust detection.

The Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) pandemic has challenged public health systems worldwide. Therefore, large-scale testing capacity is extremely important diagnosis and exclusion diagnosis. However, fixed laboratories are limited or far away from remote areas. Fortunately, MBS-Lab is characterized by high mobility and rapid on-site detection of SARS-CoV-2 nucleic acid. MBS-Lab was first used in northern Australia during a melioidosis outbreak in 1997. The MBS-Lab and a well-trained diagnostic team were dispatched to Dongchang District, Tonghua City, Jilin Province, China to assist the SARS-CoV-2 virus screening and diagnosis on January 17, 2021. Altogether, 93,952 oropharyngeal swabs samples were collected and tested among the high-risk groups and the general population in Dongchang District. Two single samples were identified as positive in the second turn screening. In the second turn screening, 3 mixed samples (10 in 1) were identified as positive; 10 mixed samples were identified as positive in the third turn screening. By resampling again, one and four cases were identified as positive, respectively. The positive cases were properly isolated and treated in hospital and avoided to visit family members, friends, colleagues and any other persons. Through this way of large-scale screening, human-human spread of SARS-CoV-2 can be effectively avoided. In addition, all staff members strictly executed multiple safety precautions and reduce exposure risks. In the end, none of the staffs was infected with SARS-CoV-2 virus or other pathogens. As an emergency facility for infectious disease control, the MBS-Lab satisfies the requirements of ports and other remote areas far from fixed laboratories and supplements the capabilities of fixed laboratories.

Clostridium perfringens (C. perfringens) is an important foodborne pathogen that can cause diseases such as gas gangrene and necrotizing enteritis in a variety of economic animals, seriously affecting public health and the economic benefits and healthy development of the livestock and poultry breeding industry. Perfringolysin O (PFO) is an important virulence factor of C. perfringens and plays critical roles in necrotic enteritis and gas gangrene, rendering it an ideal target for developing new drugs against infections caused by this pathogen. In this study, based on biological activity inhibition assays, oligomerization tests and computational biology assays, we found that the foodborne natural component piceatannol reduced pore-forming activity with an inhibitory ratio of 83.84% in the concentration of 16 µg/mL (IC50 = 7.83 µg/mL) by binding with PFO directly and changing some of its secondary structures, including 3-Helix, A-helix, bend, and in turn, ultimately affecting oligomer formation. Furthermore, we confirmed that piceatannol protected human intestinal epithelial cells from the damage induced by PFO with LDH release reduced by 38.44% at 16 µg/mL, based on a cytotoxicity test. By performing an animal experiment, we found the C. perfringens clones showed an approximate 10-fold reduction in infected mice. These results suggest that piceatannol may be a candidate for anti-C. perfringens drug development.

Klebsiella pneumoniae (K. pneumoniae) is an important nosocomial and community acquired opportunistic pathogen which causes various infections. The emergence of multi-drug resistant (MDR) K. pneumoniae and carbapenem-resistant hypervirulent K. pneumoniae (CR-hvKP) has brought more severe challenge to the treatment of K. pneumoniae infection. In this study, a novel bacteriophage that specifically infects K. pneumoniae was isolated and named as vB_KpnM_P-KP2 (abbreviated as P-KP2). The biological characteristics of P-KP2 and the bioinformatics of its genome were analyzed, and then the therapeutic effect of P-KP2 was tested by animal experiments. P-KP2 presents high lysis efficiency in vitro. The genome of P-KP2 shows homology with nine phages which belong to “KP15 virus” family and its genome comprises 172,138 bp and 264 ORFs. Besides, P-KP2 was comparable to gentamicin in the treatment of lethal pneumonia caused by K. pneumoniae W-KP2 (K47 serotype). Furthermore, the combined treatment of P-KP2 and gentamicin completely rescued the infected mice. Therefore, this study not only introduces a new member to the phage therapeutic library, but also serves as a reference for other phage-antibiotic combinations to combat MDR pathogens.

Bovine mastitis, an inflammatory disease that occurs frequently in early lactation or the dry period, is primarily caused by bacterial infections. There is growing evidence that Aerococcus viridans (A. viridans) is becoming an important cause of bovine mastitis. The treatment of bovine mastitis is primarily based on antibiotics, which not only leads to a large economic burden but also the development of antibiotic resistance. On the other hand, bacteriophages present a promising alternative treatment strategy. The object of this study was to evaluate the potential of a previously isolated A. viridans phage vB_AviM_AVP (AVP) as an anti-mastitis agent in an experimental A. viridans-induced murine mastitis model. A. viridans N14 was isolated from the milk of clinical bovine mastitis and used to establish a mastitis model in mice. We demonstrated that administration of phage AVP significantly reduced colony formation by A. viridans and alleviated damage to breast tissue. In addition, reduced inflammation was indicated by decreased levels of inflammatory cytokines (TNF-α, IL-1β, and IL-6) and myeloperoxidase (MPO) activity in the phage-treated group compared to those in the phosphate buffered saline (PBS)-treated group. To the best of our knowledge, this report is the first to show the potential use of phages as a treatment for A. viridans-induced mastitis.

Yersinia enterocolitica is generally considered an important food-borne pathogen worldwide, especially in the European Union. A lytic Yersinia phage X1 (Viruses; dsDNA viruses, no RNA stage; Caudovirales; and Myoviridae) was isolated. Phage X1 showed a broad host range and could effectively lyse 27/51 Y. enterocolitica strains covering various serotypes that cause yersiniosis in humans and animals (such as serotype O3 and serotype O8). The genome of this phage was sequenced and analyzed. No toxin, antibiotic-resistance or lysogeny related modules were found in the genome of phage X1. Studies of phage stability confirmed that X1 had a high tolerance toward a broad range of temperatures (4–60°C) and pH values (4–11) for 1 h. The ability to resist harsh acidic conditions and enzymatic degradation in vitro demonstrated that phage X1 is suitable for oral administration, and in particular, that this phage can pass the stomach barrier and efficiently reach the intestine in vivo without losing infectious ability. The potential of this phage against Y. enterocolitica infection in vitro was studied. In animal experiments, a single oral administration of phage X1 at 6 h post infection was sufficient to eliminate Y. enterocolitica in 33.3% of mice (15/45). In addition, the number of Y. enterocolitica strains in the mice was also dramatically reduced to approximately 103 CFU/g after 18 h compared with 107 CFU/g in the mice without phage treatment. Treatment with phage X1 showed significant improvement by intestinal histopathologic observations. Moreover, proinflammatory cytokine levels (IL-6, TNF-α, and IL-1β) were significantly reduced (P < 0.05). These results indicate that phage X1 is a promising candidate to control infection by Y. enterocolitica in vivo.

Infections caused by antibiotic-resistant Escherichia coli are a threat to human and animal health globally. Phage therapy has made great progress for the treatment of drug-resistant infections, but it is still unclear whether E. coli resistance to antibiotics could change the lysis ability of phages. In this study, we demonstrate that over expression of AmpC, an important β-lactamase for ampicillin resistance, promotes lysis of E. coli by phage utilizing OmpA as a receptor. E. coli strains expressing more AmpC showed higher levels of OmpA, an E. coli outer membrane protein known to serve as a receptor for T-even phages, which resulted in increased adsorption and lysis by the phage tested in this study. These data demonstrate that increased ampicillin resistance can increase the sensitivity of E. coli to some lytic phage, which provides evidence for the feasibility of synergistic application of phage and antibiotics.

Abstract Distal tibiofibular syndesmosis (DTS) has wide anatomic variability in depth of incisura fibularis and shape of tibial tubercles. We designed a 3-year prospective cohort study of 300 young physical training soldiers in an Army Physical Fitness School. Ankle computed tomography (CT) scans showed that 56% of the incisura fibularis were a “C” shape, 25% were a “1” shape, and 19% were a “Г” shape. Furthermore, we invited a randomly selected subcohort of 6 participants in each shape of DTS to undergo a three-dimensional (3D) laser scanning. The “1” shape group showed widest displacement range of the DTS in the y-axis, along with the range of motion (ROM) on the position more than 20° of the ankle dorsiflexion, inversion and eversion. During the 3-year study period, 23 participants experienced recurrent lateral ankle sprains. 7 cases of the incisura fibularis were “C” shape, 13 cases were “1” shape, and 3 cases were “Г” shape. The “1” shape showed highest risk among the three shapes in incident recurrent lateral ankle sprains. We propose that it is possible to classify shapes of DTS according to the shapes of incisura fibularis, and people with “1” shape may have more risk of recurrent lateral ankle sprains.

Klebsiella pneumoniae (K. pneumoniae) spp. are important nosocomial and community-acquired opportunistic pathogens, which cause various infections. We observed that K. pneumoniae strain K7 abruptly mutates to rough-type phage-resistant phenotype upon treatment with phage GH-K3. In the present study, the rough-type phage-resistant mutant named K7RR showed much lower virulence than K7. Liquid chromatography-tandem mass spectrometry (LC-MS-MS) analysis indicated that WcaJ and two undefined glycosyltransferases (GTs)- named GT-1, GT-2- were found to be down-regulated drastically in K7RR as compared to K7 strain. GT-1, GT-2, and wcaJ are all located in the gene cluster of capsular polysaccharide (CPS). Upon deletion, even of single component, of GT-1, GT-2, and wcaJ resulted clearly in significant decline of CPS synthesis with concomitant development of GH-K3 resistance and decline of virulence of K. pneumoniae, indicating that all these three GTs are more likely involved in maintenance of phage sensitivity and bacterial virulence. Additionally, K7RR and GT-deficient strains were found sensitive to endocytosis of macrophages. Mitogen-activated protein kinase (MAPK) signaling pathway of macrophages was significantly activated by K7RR and GT-deficient strains comparing with that of K7. Interestingly, in the presence of macromolecular CPS residues (>250 KD), K7(ΔGT-1) and K7(ΔwcaJ) could still be bounded by GH-K3, though with a modest adsorption efficiency, and showed minor virulence, suggesting that the CPS residues accumulated upon deletion of GT-1 or wcaJ did retain phage binding sites as well maintain mild virulence. In brief, our study defines, for the first time, the potential roles of GT-1, GT-2, and WcaJ in K. pneumoniae in bacterial virulence and generation of rough-type mutation under the pressure of bacteriophage.

By using electrochemical deposition method, and assisted with additions of PEG-400 and EDA, well-aligned ZnO nanorods and hierarchical ZnO micro-nanostructure are fabricated directly on indium doped tin oxide coated conducting glass (ITO) substrate. The shell-core Sb2S3/ZnO nanorod structure and the shell-core hierarchical Sb2S3/ZnO micro-nanostructure are prepared by chemical bath deposition method. SEM, XRD, UV-Vis and photocurrent test are used to characterize the morphology, nanostructures and their photoelectrochemical properties. The studies show that the photocurrent on the array membranes with shell-core hierarchical Sb2S3/ZnO micro-nanostructure is apparently higher than that with shell-core Sb2S3/ZnO nanorods array.

Biofilm formation, one of the most important virulence factors of pathogenic bacteria, protects bacteria against desiccation, antibiotics, phages and host immune responses. However, phage-derived depolymerases show antibiofilm activity and demonstrate great potential to treat infections caused by biofilm-forming bacteria. In this study, the Escherichia coli phage vB_EcoM_ECOO78 was isolated and characterised, and we observed its ability to lyse five out of 34 tested E. coli clinical isolates. The highest phage titre was observed at a multiplicity of infection of 10-5 and a burst size of approximately 74 plaque forming units (PFU)/infection. Electron micrographs indicated that vB_EcoM_ECOO78 belongs to the family Myoviridae. The presence of increasing halos surrounding the lysis plaques formed by vB_EcoM_ECOO78 indicated that this phage may encode a depolymerase. Based on a sequencing analysis, the complete genome of vB_EcoM_ECOO78 was found to be 41,289 bp in size, with a GC content of 53.07%. Additionally, vB_EcoM_ECOO78 has 56 predicted open reading frames, 51 (91.07%) of which are assumed to be functional. A BLAST analysis indicated that ORF42 of vB_EcoM_ECOO78 (Dpo42) has low identity with other reported phage-associated depolymerases. Dpo42 was expressed and purified as a soluble protein using E. coli BL21. The biofilm formation ability of E. coli isolates and the antibiofilm activity of Dpo42 were tested by performing spot assays and using a 96-well micro-titre plate method. Dpo42 degraded the capsular polysaccharides surrounding E. coli and exhibited dose-dependent biofilm-formation prevention activity. Based on these results, Dpo42 appears to be a novel phage-derived depolymerase that represents a new potential strategy for preventing E. coli biofilm formation.

Enterococcus faecalis is becoming an increasingly important opportunistic pathogen worldwide, especially because it can cause life-threatening nosocomial infections. Treating E. faecalis infections has become increasingly difficult because of the prevalence of multidrug-resistant E. faecalis strains. Because bacteriophages show specificity for their bacterial hosts, there has been a growth in interest in using phage therapies to combat the rising incidence of multidrug-resistant bacterial infections. In this study, we isolated a new lytic phage, EF-P29, which showed high efficiency and a broad host range against E. faecalis strains, including vancomycin-resistant strains. The EF-P29 genome contains 58,984 bp (39.97% G+C), including 101 open reading frames, and lacks known putative virulence factors, integration-related proteins or antibiotic resistance determinants. In murine experiments, the administration of a single intraperitoneal injection of EF-P29 (4 × 105 PFU) at 1 h after challenge was sufficient to protect all mice against bacteremia caused by infection with a vancomycin-resistant E. faecalis strain (2 × 109 CFU/mouse). E. faecalis colony counts were more quickly eliminated in the blood of EF-P29-protected mice than in unprotected mice. We also found that exogenous E. faecalis challenge resulted in enrichment of members of the genus Enterococcus (family Enterococcaceae) in the guts of the mice, suggesting that it can enter the gut and colonize there. The phage EF-P29 reduced the number of colonies of genus Enterococcus and alleviated the gut microbiota imbalance that was caused by E. faecalis challenge. These data indicate that the phage EF-P29 shows great potential as a therapeutic treatment for systemic VREF infection. Thus, phage therapies that are aimed at treating opportunistic pathogens are also feasible. The dose of phage should be controlled and used at the appropriate level to avoid causing imbalance in the gut microbiota.

An optimal sizing model of the battery energy storage system (BESS) for large-scale wind farm adapting to the scheduling plan is proposed in this paper. Based on the analysis of the variability and uncertainty of wind output, the cost of auxiliary services of systems that are eased by BESS is quantized and the constraints of BESS accounting for the effect of wind power on system dispatching are proposed. Aiming to maximum the benefits of wind-storage union system, an optimal capacity model considering BESS investment costs, wind curtailment saving, and auxiliary services compensation is established. What’s more, the effect of irregular charge/discharge process on the life cycle of BESS is considered into the optimal model by introducing an equivalent loss of the cycle life. Finally, based on the typical data of a systems, results show that auxiliary services compensation can encourage wind farm configuration BESS effectively. Various sensitivity analyses are performed to assess the effect of the auxiliary services compensation, on-grid price of wind power, investment cost of BESS, cycle life of BESS, and wind uncertainty reserve level of BESS on this optimal capacity.

Chronic hepatitis B infection (CHB) is characterized by sub-optimal T cell responses to viral antigens. A therapeutic vaccine capable of restoring these immune responses could potentially improve HBsAg seroconversion rates in the setting of direct acting antiviral therapies. A yeast-based immunotherapy (Tarmogen) platform was used to make a vaccine candidate expressing hepatitis B virus (HBV) X, surface (S), and Core antigens (X-S-Core). Murine and human immunogenicity models were used to evaluate the type and magnitude of HBV-Ag specific T cell responses elicited by the vaccine. C57BL/6J, BALB/c, and HLA-A*0201 transgenic mice immunized with yeast expressing X-S-Core showed T cell responses to X, S and Core when evaluated by lymphocyte proliferation assay, ELISpot, intracellular cytokine staining (ICS), or tumor challenge assays. Both CD4+ and CD8+ T cell responses were observed. Human T cells transduced with HBc18-27 and HBs183-91 specific T cell receptors (TCRs) produced interferon gamma (IFNγ following incubation with X-S-Core-pulsed dendritic cells (DCs). Furthermore, stimulation of peripheral blood mononuclear cells (PBMCs) isolated from CHB patients or from HBV vaccine recipients with autologous DCs pulsed with X-S-Core or a related product (S-Core) resulted in pronounced expansions of HBV Ag-specific T cells possessing a cytolytic phenotype. These data indicate that X-S-Core-expressing yeast elicit functional adaptive immune responses and supports the ongoing evaluation of this therapeutic vaccine in patients with CHB to enhance the induction of HBV-specific T cell responses.