Sex differences in LDL-C reduction response to evolocumab: A propensity score matching analysis.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) have been shown to improve cardiovascular outcomes by reducing low-density lipoprotein cholesterol (LDL-C). However, sex differences in the efficacy of evolocumab remain unclear. This study aimed to investigate sex differences in the efficacy of evolocumab using real-world data. METHOD: Data were collected from the First Affiliated Hospital of Guangxi Medical University. A total of 416 eligible patients were selected from 1463 patients treated with evolocumab for secondary prevention. Clinical data, including individual characteristics and lipids profiles, were recorded. Propensity score matching (PSM) was used to control for potential confounders, with covariates including age, body mass index, smoking status, and diabetes. All eligible participants were propensity-matched 1:1 for female versus male with a match tolerance of 0.02. The efficacy of evolocumab in females and males was compared by PSM-adjusted analysis. RESULTS: In the PSM analysis, a significant difference was found in the relative percentage reduction of LDL-C between females and males (-42.7% vs. -54.4%, p < 0.001). In addition, the absolute LDL-C reduction was lower in females compared to males (interquartile range: -1.5 [-2.2, -0.8] mmol/L vs. -1.9 [-2.5, -1.0] mmol/L, p = 0.018). The rate of target LDL-C attainment was lower in females than in males after treatment with evolocumab (21.6% vs. 39.8%, p = 0.009). CONCLUSION: These results suggest that males have a better response to evolocumab in term of LDL-C reduction compared to females.

Digital-Twin Predictive Control of Nonlinear Systems With Time Delays, Unknown Dynamics, and Communication Delays.

With the advancement of computing technology and big data technology, digital twins have gradually been applied in various fields, such as manufacturing, energy, and healthcare. This article studies the predictive control of nonlinear dynamic systems using digital twins. Based on a digital-twin control system framework, predictive control is discussed for three different nonlinear systems with time delays: 1) known nonlinear systems; 2) unknown nonlinear systems; and 3) unknown nonlinear cyber-physical systems. Both a digital-twin predictive control strategy and a digital-twin control predictor are proposed to compensate for time delays and communication delays actively. With the strategy and predictor, the digital-twin controller of a time-delay nonlinear system can be designed to achieve the desired performance based on the nonlinear system without time delays, which vastly simplifies the controller design procedure. A digital model is constructed using data to deal with unknown nonlinear dynamics. The three different closed-loop digital-twin predictive control systems are analyzed to derive a unified stability criterion. The simulation results show how the proposed digital-twin predictive control method performs well for nonlinear systems with time delays, unknown dynamics, and/or communication delays.

A Lanthanide-Incorporated Phospho(III)tungstate Aggregate Constructed from [HPIIIW8O31]10- and [W11O39]12- Building Blocks and Its Nanocomposite with CdS for Ultrasensitive Photoelectrochemical Detection of Oxytetracycline.

A novel tartronic acid decorated hexa-CeIII-incorporated phospho(III)tungstate aggregate (C4H12NO)6Na18H2[(HPW8O31)2[W11O39]2(H2TAD)4(H2O)4W4Ce6H2P2O14]·84H2O (1, H3TAD = tartronic acid) was synthesized by a one-step assembly strategy. Its main skeleton is constructed from two [W11O39]12- fragments, two [HPIIIW8O31]10- segments and one H2TAD--ornamented dodecanuclear heterometallic [W4Ce6H2PIII2O14(H2TAD)4(H2O)4]18+ cluster. In the structure, the [HPIIIO3]2- groups not only work as the heteroatom template to induce the formation of lacunary [HPIIIW8O31]10- segments but also function as the connector to bridge Ce3+ cations. With the help of a reaction strategy of combining ultrasonication treatment with the continuous ion layer adsorption method, the 1/CdS composite was constructed and exhibits prominent photoelectrochemical activity. The 1/CdS composite was used as a photoelectrochemical sensor for oxytetracycline detection at 0 V (vs Ag/AgCl), which displays excellent properties with quick response and low limit of detection (0.042 nM). This work can provide some helpful references in the construction of novel PIII-induced polyoxometalates consisting of different building blocks and can extend the applications of polyoxometalate-based nanocomposites into photoelectrochemical detection for antibiotics as well as biomolecules.

Annexin A2: A Double-Edged Sword in Pathogen Infection.

Annexin A2 (ANXA2) is a multifunctional calcium- and phospholipid-binding protein that plays an important role in various cells. During pathogen infections, ANXA2 modulates the nuclear factor kappa-B (NF-κB) and cell apoptosis signaling pathways and guides the chemotaxis of inflammatory cells toward inflammation sites, thereby protecting the host organism through the modulation of the inflammatory response. In addition, ANXA2 can regulate immune responses, and in certain pathogen infections, it can interact with pathogen proteins to facilitate their invasion and proliferation. This review provides an overview of the research progress on how ANXA2 regulates pathogen infections.

Nitazoxanide synergizes polymyxin B against Escherichia coli by depleting cellular energy.

The rapid expansion of antibiotic-resistant bacterial diseases is a global burden on public health. It makes sense to repurpose and reposition already-approved medications for use as supplementary agents in synergistic combinations with existing antibiotics. Here, we demonstrate that the anthelmintic drug nitazoxanide (NTZ) synergistically enhances the effectiveness of the lipopeptide antibiotic polymyxin B in inhibiting gram-negative bacteria, including those resistant to polymyxin B. Mechanistic investigations revealed that nitazoxanide inhibited calcium influx and cell membrane depolarization, enhanced the affinity between polymyxin B and the extracellular membrane, and promoted intracellular ATP depletion and an increase in reactive oxygen species (ROS), thus enhancing the penetration and disruption of the Escherichia coli cell membrane by polymyxin B. The transcriptomic analysis revealed that the combination resulted in energy depletion by inhibiting both aerobic and anaerobic respiration patterns in bacterial cells. The increased bactericidal effect of polymyxin B on the E. coli ∆nuoC strain further indicates that NuoC could be a promising target for nitazoxanide. Furthermore, the combination of nitazoxanide and polymyxin B showed promising therapeutic effects in a mouse infection model infected with E. coli. Taken together, these results demonstrate the potential of nitazoxanide as a novel adjuvant to polymyxin B, to overcome antibiotic resistance and improve therapeutic outcomes in refractory infections.IMPORTANCEThe rapid spread of antibiotic-resistant bacteria poses a serious threat to public health. The search for potential compounds that can increase the antibacterial activity of existing antibiotics is a promising strategy for addressing this issue. Here, the synergistic activity of the FDA-approved agent nitazoxanide (NTZ) combined with polymyxin B was investigated in vitro using checkerboard assays and time-kill curves. The synergistic mechanisms of the combination of nitazoxanide and polymyxin B were explored by fluorescent dye, transmission electron microscopy (TEM), and transcriptomic analysis. The synergistic efficacy was evaluated in vivo by the Escherichia coli and mouse sepsis models. These results suggested that nitazoxanide, as a promising antibiotic adjuvant, can effectively enhance polymyxin B activity, providing a potential strategy for treating multidrug-resistant bacteria.

Mechanistic study on the promotion of Ca2+ leaching in steel slag through high-temperature solid waste modification.

Indirect carbonation of steel slag is an effective method for CO2 storage, reducing emissions, and promoting cleaner production in the steel industry. However, challenges remain, such as low Ca2+ leaching rates and slag management complexities arising from variations in mineral compositions. To address this, a high-temperature modification process is proposed to alter the mineral composition and facilitate the synergistic utilization of calcium and iron. This study delves into the effects of various solid waste modifications on the leaching of Ca2+ and the total iron content within steel slag. Results show that high-basicity modified slag forms Ca2(Al, Fe)2O5, reducing calcium leaching. Low-alkalinity modified slag produces calcium-rich aluminum minerals and also reduces the leaching of Ca2+ ions. At a basicity of 2.5, coal gangue, fly ash, and blast slag achieve maximum Ca2+ leaching rates of 88.93%, 89.46%, and 90.17%, respectively, with corresponding total iron contents of 41.46%, 37.72%, and 35.29%. Upgraded coal gangue exhibits a 50.02% increase in calcium leaching and a 15.58% increase in total iron content compared to the original slag. This enhances CO2 fixation and iron resource utilization. Overall, the proposed indirect carbonation and iron enrichment modification offer a novel approach for the resource utilization and environmental stability of steel slag.

Data-Driven Distributed Predictive Control for Voltage Regulation and Current Sharing in DC Microgrids With Communication Constraints.

The use of nonideal communication networks makes communication constraints become a topical issue in the research of dc microgrids. How to design a distributed secondary control scheme for voltage recovery and accurate current sharing in islanded dc microgrids subject to communication constraints is of interest in this article. In order to restore the bus voltage to the rated value, a nonlinear element is first introduced into the primary control layer. Then, the closed-loop system of primary control is modeled as a data-driven time-varying linear system. Based on the established model, considering communication constraints, a distributed secondary predictive control strategy is developed to achieve accurate current sharing. While actively compensating for network delays and packet losses, the proposed method renders mathematical physical models unnecessary for the traditional predictive control, and simultaneously completes the multitask in dc microgrids. Finally, several case studies are conducted on a hardware microgrid experimental platform, which not only verifies the effectiveness of the designed data-driven predictive control strategy but also tests microgrid properties such as the plug-and-play ability.

2,5-Thiophenedicarboxylic Acid Bridging Hexameric CeIII-Substituted Selenotungstate and Its Application for Detecting Mucin 1.

The development of polyoxometalate chemistry not only is derived from the continuous discovery of novel polyoxometalates (POMs) but also stems from the exploitation of their new functionalities. In this work, we obtained a rigid sulfur-containing heterocyclic ligand-linking aggregate [N(CH3)4]10Na6H6[Ce8(H2O)26W8(HTDA)2(TDA)2O20][SeW4O18]2[SeW9O33]4·112H2O (1) (H2TDA = 2,5-thiophenedicarboxylic acid). Its polyanionic unit consists of one [Ce4(H2O)13W4O10(HTDA)(TDA)O10]18+ cluster and two kinds of Keggin-type [SeW4O18] and [SeW9O33] segments. It is noteworthy that H2TDA ligands not only work as connectors to link two symmetrical {[Ce4(H2O)13W4(HTDA)(TDA)O10][SeW4O18][SeW9O33]2}11- units but also function as ornaments to graft to the polyanionic backbone. Furthermore, 1 and 3,4-ethylenedioxythiophene (EDOT) were deposited on the glassy carbon electrode (GCE) by the electropolymerization (EPM) method, resulting in a 1-poly(3,4-ethylenedioxythiophene) (1-PEDOT) composite film, which can provide sufficient binding sites to immobilize Au nanoparticles (Au NPs). Hereafter, the Au NPs-immobilized 1-PEDOT modified electrode (Au/1-PEDOT/GCE) was used to construct an electrochemical aptasensor to detect mucin 1, showing a low detection limit of 29.5 fM in the Tris solution. This work not only demonstrates that rigid heterocyclic ligands are beneficial for the creation of novel rare-earth-substituted selenotungstate hybrids but also provides more enlightenment for POM-based materials used for electrochemical detection of cancer markers.

ERK signaling expands mammalian cortical radial glial cells and extends the neurogenic period.

The molecular basis for cortical expansion during evolution remains largely unknown. Here, we report that fibroblast growth factor (FGF)-extracellular signal-regulated kinase (ERK) signaling promotes the self-renewal and expansion of cortical radial glial (RG) cells. Furthermore, FGF-ERK signaling induces bone morphogenic protein 7 (Bmp7) expression in cortical RG cells, which increases the length of the neurogenic period. We demonstrate that ERK signaling and Sonic Hedgehog (SHH) signaling mutually inhibit each other in cortical RG cells. We provide evidence that ERK signaling is elevated in cortical RG cells during development and evolution. We propose that the expansion of the mammalian cortex, notably in human, is driven by the ERK-BMP7-GLI3R signaling pathway in cortical RG cells, which participates in a positive feedback loop through antagonizing SHH signaling. We also propose that the relatively short cortical neurogenic period in mice is partly due to mouse cortical RG cells receiving higher SHH signaling that antagonizes ERK signaling.

Robust Cooperative Control for Heterogeneous Uncertain Nonlinear High-Order Fully Actuated Multiagent Systems.

This research is intended to address a robust cooperative control problem of heterogeneous uncertain nonlinear high-order fully actuated multiagent systems (HUN-HOFAMASs). A nonlinear HOFA system model is used to describe the multiagent systems (MASs) with heterogeneous uncertain nonlinear dynamics, which is called the HUN-HOFAMASs. A predictive terminal sliding-mode control-based robust cooperative control scheme is presented to address this problem. In this scheme, heterogeneous nonlinear dynamics of original system are offset to establish a linear constant HOFA system with the help of full actuation feature. Then, a terminal sliding-mode variable for enhancing the system robustness is introduced to handle the uncertainties. Furthermore, a linear incremental prediction model is developed in a HOFA form by means of a Diophantine equation. According to this model, the multistep terminal sliding-mode predictions are yielded to optimize the robust cooperative control performance and compensate for the network-induced communication constraints in the feedback and forward channels. Based on a linear matrix inequality (LMI) method, a necessary and sufficient criterion is derived to discuss the simultaneous consensus and stability of closed-loop HUN-HOFAMASs. The simulation and comparison results of cooperative flying around of multiple spacecraft system are shown to illustrate the capability and advantage of the presented predictive terminal sliding-mode control for robust cooperative control.

A Two Phases Multiobjective Trajectory Optimization Scheme for Multi-UGVs in the Sight of the First Aid Scenario.

Timely delivery of first aid supplies is significant to saving lives when an accident happens. Among the promising solutions provided for such scenarios, the application of unmanned vehicles has attracted ever more attention. However, such scenarios are often very complex, while the existing studies have not fully addressed the trajectory optimization problem of multiple unmanned ground vehicles (multi-UGVs) against the scenario. This study focuses on multi-UGVs trajectory optimization in the sight of first aid supply delivery tasks in mass accidents. A two-stage completely decoupling fuzzy multiobjective optimization strategy is designed. On the first stage, with the proposed timescale involved tridimensional tunneled collision-free trajectory (TITTCT) algorithm, collision-free coarse tunnels are build within a tridimensional coordinate system, respectively, for the UGVs as the corresponding configuration space for a further multiobjective optimization. On the second stage, a fuzzy multiobjective transcription method is designed to solve the decoupled optimal control problem (OCP) within the configuration space with the consideration of priority constrains. Following the two-stage design, the computational time is significantly reduced when achieving an optimal solution of the multi-UGV trajectory planning, which is crucial in a first aid task. In addition, other objectives are optimized with the aspiration level reflected. Simulation studies and experiments have been curried out to testify the effectiveness and the improved computational performance of the proposed design.

Consensus-based secondary control for DC microgrids with communication delays via a networked predictive control strategy.

In today's cyber-physical microgrid systems, the consensus-based secondary control is generally utilized to settle the voltage deviation and rough current allocation issues at the primary control level. However, time delays follow inevitably the introduction of sparse communication networks, and most existing works adopt passive tolerance approaches. To actively alleviate the unavoidable delay effect in microgrids' communication networks, a networked predictive control (NPC) strategy is proposed for an islanded DC microgrid subject to time delays in this paper. Firstly, the predictive approaches for both voltage and current are developed based on the cyber-physical microgrid model. Unlike the practice of passively tolerating time delays, the NPC strategy is proposed to actively compensate for the effect of communication delays by estimating real-time voltage and current values using the previously obtained prediction models. Moreover, to prove the generality of the developed method, the microgrid systems' stability can be derived from the Schur stability of the closed-loop system, thus the DC microgrid can achieve voltage regulation and proportional current sharing simultaneously. Finally, the performance of our method against the time delay effect is validated by extensive experiments on an islanded 48-V DC microgrid system, in terms of its feasibility, delay tolerance ability, and robustness to load changes and communication faults. Experimental results demonstrate the effectiveness and superiority of the NPC strategy.

Mathematically Improved XGBoost Algorithm for Truck Hoisting Detection in Container Unloading.

Truck hoisting detection constitutes a key focus in port security, for which no optimal resolution has been identified. To address the issues of high costs, susceptibility to weather conditions, and low accuracy in conventional methods for truck hoisting detection, a non-intrusive detection approach is proposed in this paper. The proposed approach utilizes a mathematical model and an extreme gradient boosting (XGBoost) model. Electrical signals, including voltage and current, collected by Hall sensors are processed by the mathematical model, which augments their physical information. Subsequently, the dataset filtered by the mathematical model is used to train the XGBoost model, enabling the XGBoost model to effectively identify abnormal hoists. Improvements were observed in the performance of the XGBoost model as utilized in this paper. Finally, experiments were conducted at several stations. The overall false positive rate did not exceed 0.7% and no false negatives occurred in the experiments. The experimental results demonstrated the excellent performance of the proposed approach, which can reduce the costs and improve the accuracy of detection in container hoisting.

Observer-based HOFA predictive cooperative control for networked multi-agent systems under time-variant communication constraints.

This research focuses on a cooperative control problem for networked multi-agent systems (NMASs) under time-variant communication constraints (containing time-variant communication delays and time-variant data losses) in the forward and feedback channels. From the perspective of high-order fully actuated (HOFA) system theory, a HOFA system model is adopted to describe the NMAS, which is called the networked HOFA multi-agent system (NHOFAMAS). Because of complicated working scenarios over the network, the states of NMASs are immeasurable and the communication constraints are always present, such that an observer-based HOFA predictive control (OB-HOFAPC) method is designed to implement the cooperative control when existing the immeasurable states and time-variant communication constraints. In this method, a HOFA observer is established to estimate the immeasurable states for constructing a consensus control protocol. Then, an incremental prediction model (IPM) in a HOFA form is developed via a Diophantine equation to take the place of a reduced-order prediction model. Through this IPM, multi-step output ahead predictions are derived to optimize the cooperative control performance and compensate for time-variant communication constraints in real-time. The depth discussion gives a sufficient and necessary criterion to analyze the simultaneous consensus and stability for closed-loop NHOFAMASs. The capability and advantage of OB-HOFAPC method are illustrated via numerical simulation and experimental verification on a cooperative flying-around task of three air-bearing spacecraft simulators.

Secure Predictive Coordinated Control of High-Order Fully Actuated Networked Multiagent Systems Under Random DoS Attacks.

This research addresses a coordinated control problem for high-order fully actuated networked multiagent systems (HOFANMASs) under random denial-of-service (DoS) attacks. A type of Bernoulli processes is exploited to denote the successful rate of launching random DoS attacks happened to the forward and feedback channels. When acting these attacks successfully, random data losses and disorders are caused in the forward and feedback channels. A high-order fully actuated (HOFA) secure predictive coordinated control scheme is provided to achieve the security coordination. In this scheme, a dynamic model of networked multiagent system is established with the help of a HOFA system model, which is called the HOFANMAS. Then, a prediction model in an incremental HOFA (IHOFA) form is developed by means of a Diophantine equation, which aims at constructing the multistep ahead output predictions for the optimization of coordinated control performance and the compensation of random data losses and disorders. Furthermore, a necessary and sufficient condition is proposed to analyze the consensus and stability of closed-loop HOFANMASs. The effectiveness and superiority of HOFA secure predictive control scheme can be demonstrated via simulated and experimental results of formation control for three air-bearing spacecraft (ABS) simulators.

Gut microbiota and serum metabolome reveal the mechanism by which TCM polysaccharides alleviate salpingitis in laying hens challenged by bacteria.

This paper aimed to evaluate the effect of 3 kinds of TCM polysaccharides instead of antibiotics in preventing salpingitis in laying hens. After feeding the laying hens with Lotus leaf polysaccharide, Poria polysaccharide, and Epimedium polysaccharide, mixed bacteria (E. coli and Staphylococcus aureus) were used to infect the oviduct to establish an inflammation model. Changes in antioxidant, serum immunity, anti-inflammatory, gut microbiota, and serum metabolites were evaluated. The results showed that the 3 TCM polysaccharides could increase the expression of antioxidant markers SOD, GSH, and CAT, and reduce the accumulation of MDA in the liver; the contents of IgA and IgM in serum were increased. Decreased the mRNA expression of TLR4, NFκB, TNF-α, IFN-γ, IL1ß, IL6, and IL8, and increased the mRNA expression of anti-inflammatory factor IL5 in oviduct tissue. 16sRNA high-throughput sequencing revealed that the 3 TCM polysaccharides improved the intestinal flora disturbance caused by bacterial infection, increased the abundance of beneficial bacteria such as Bacteroides and Actinobacillus, and decreased the abundance of harmful bacteria such as Romboutsia, Turicibacter, and Streptococcus. Metabolomics showed that the 3 TCM polysaccharides could increase the content of metabolites such as 3-hydroxybutyric acid and isobutyl-L-carnitine, and these results could alleviate the further development of salpingitis. In conclusion, the present study has found that using TCM polysaccharides instead of antibiotics was a feasible way to prevent bacterial salpingitis in laying hens, which might make preventing this disease no longer an issue for breeding laying hens.

Zero-Strain Na3 V2 (PO4 )2 F3 @Rgo/CNT Composite as a Wide-Temperature-Tolerance Cathode for Na-Ion Batteries with Ultrahigh-Rate Performance.

Sodium-ion batteries (SIBs) are widely considered a hopeful alternative to lithium-ion battery technology. However, they still face challenges, such as low rate capability, unsatisfactory cycling stability, and inferior variable-temperature performance. In this study, a hierarchical Na3 V2 (PO4 )2 F3 (NVPF) @reduced graphene oxide (rGO)/carbon nanotube (CNT) composite (NVPF@rGO/CNT) is successfully constructed. This composite features 0D Na3 V2 (PO4 )2 F3 nanoparticles are coated by a cross-linked 3D conductive network composed of 2D rGO and 1D CNT. Furthermore, the intrinsic Na+ storage mechanism of NVPF@rGO/CNT through comprehensive characterizations is unveiled. The synthesized NVPF@rGO/CNT exhibits fast ionic/electronic transport and excellent structural stability within wide working temperatures (-40-50 °C), owing to the zero-strain NVPF and the coated rGO/CNT conductive network that reduces diffusion distance for ions and electrons. Moreover, the stable integration between NVPF and rGO/CNT enables outstanding structural stability to alleviate strain and stress induced during the cycle. Additionally, a practice full cell is assembled employing a hard carbon anode paired with an NVPF@rGO/CNT cathode, which provides a decent capacity of 105.2 mAh g-1 at 0.2 C, thereby attaining an ideal energy density of 242.7 Wh kg-1 . This work provides valuable insights into developing high-energy and power-density cathode materials for SIBs.

BMP7 expression in mammalian cortical radial glial cells increases the length of the neurogenic period.

The seat of human intelligence is the human cerebral cortex, which is responsible for our exceptional cognitive abilities. Identifying principles that lead to the development of the large-sized human cerebral cortex will shed light on what makes the human brain and species so special. The remarkable increase in the number of human cortical pyramidal neurons and the size of the human cerebral cortex is mainly because human cortical radial glial cells, primary neural stem cells in the cortex, generate cortical pyramidal neurons for more than 130 days, whereas the same process takes only about 7 days in mice. The molecular mechanisms underlying this difference are largely unknown. Here, we found that bone morphogenic protein 7 (BMP7) is expressed by increasing the number of cortical radial glial cells during mammalian evolution (mouse, ferret, monkey, and human). BMP7 expression in cortical radial glial cells promotes neurogenesis, inhibits gliogenesis, and thereby increases the length of the neurogenic period, whereas Sonic Hedgehog (SHH) signaling promotes cortical gliogenesis. We demonstrate that BMP7 signaling and SHH signaling mutually inhibit each other through regulation of GLI3 repressor formation. We propose that BMP7 drives the evolutionary expansion of the mammalian cortex by increasing the length of the neurogenic period.

Feeding behavior and hormoligosis associated with imidacloprid resistance in Asian citrus psyllid, Diaphorina citri.

Imidacloprid is a neonicotinoid insecticide used for managing the Asian citrus psyllid, Diaphorina citri Kuwayama, which serves as vector of phytopathogens causing citrus greening. However, development of resistance to neonicotinoids among populations of D. citri has coincided with occasional control failures in the field. The objectives of this research were to (1) survey current levels of imidacloprid resistance in Florida citrus; (2) compare feeding behavior between imidacloprid-resistant and susceptible D. citri using electrical penetration graph recordings, and (3) investigate the possible amplification of insecticide hormoligosis associated with resistance. Field surveys confirmed that the susceptibility of D. citri populations to imidacloprid has decreased in commercial Florida citrus groves compared with a laboratory-susceptible population. Following 12 generations of selection, resistance to imidacloprid increased by 438 fold compared with the susceptible strain. Imidacloprid-susceptible D. citri feeding on citrus exhibited significantly more bouts associated with intercellular pathway (C), phloem penetration (D), phloem salivation (E1), and nonprobing (Np) activities than imidacloprid-resistant counterparts. However, there were no differences observed in the frequency or duration of phloem ingestion or xylem feeding between susceptible and resistant D. citri. There was no statistical difference in fecundity between resistant and susceptible strains. However, the fecundity of imidacloprid-susceptible female D. citri treated with a sublethal concentration of imidacloprid (LC25 ) increased significantly compared with controls, while such hormoligosis was less pronounced among imidacloprid-resistant psyllids. Our results suggest that imidacloprid-resistant psyllids may cease feeding sooner than susceptible counterparts following sublethal exposure to this insecticide, indicative of a behavioral resistance mechanism.

C500 variants conveying complete mucosal immunity against fatal infections of pigs with Salmonella enterica serovar Choleraesuis C78-1 or F18+ Shiga toxin-producing Escherichia coli.

Salmonella enterica serovar Choleraesuis (S. Choleraesuis) C500 strain is a live, attenuated vaccine strain that has been used in China for over 40 years to prevent piglet paratyphoid. However, this vaccine is limited by its toxicity and does not offer protection against diseases caused by F18+ Shiga toxin-producing Escherichia coli (STEC), which accounts for substantial economic losses in the swine industry. We recently generated a less toxic derivative of C500 strain with both asd and crp deletion (S. Choleraesuis C520) and assessed its efficacy in mice. In addition, we demonstrate that C520 is also less toxic in pigs and is effective in protecting pigs against S. Choleraesuis when administered orally. To develop a vaccine with a broader range of protection, we prepared a variant of C520 (S. Choleraesuis C522), which expresses rSF, a fusion protein comprised of the fimbriae adhesin domain FedF and the Shiga toxin-producing IIe B domain antigen. For comparison, we also prepared a control vector strain (S. Choleraesuis C521). After oral vaccination of pigs, these strains contributed to persistent colonization of the intestinal mucosa and lymphoid tissues and elicited both cytokine expression and humoral immune responses. Furthermore, oral immunization with C522 elicited both S. Choleraesuis and rSF-specific immunoglobulin G (IgG) and IgA antibodies in the sera and gut mucosa, respectively. To further evaluate the feasibility and efficacy of these strains as mucosal delivery vectors via oral vaccination, we evaluated their protective efficacy against fatal infection with S. Choleraesuis C78-1, as well as the F18+ Shiga toxin-producing Escherichia coli field strain Ee, which elicits acute edema disease. C521 conferred complete protection against fatal infection with C78-1; and C522 conferred complete protection against fatal infection with both C78-1 and Ee. Our results suggest that C520, C521, and C522 are competent to provide complete mucosal immune protection against fatal infection with S. Choleraesuis in swine and that C522 equally qualifies as an oral vaccine vector for protection against F18+ Shiga toxin-producing Escherichia coli.