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Podocyte injury is a critical event in the pathogenesis of diabetic nephropathy (DN). Hyperglycemia, oxidative stress, inflammation, and other factors contribute to podocyte damage in DN. In this study, we demonstrate that signaling regulatory protein alpha (SIRPα) plays a pivotal role in regulating the metabolic and immune homeostasis of podocytes. Deletion of SIRPα in podocytes exacerbates, while transgenic overexpression of SIRPα alleviates, podocyte injury in experimental DN mice. Mechanistically, SIRPα downregulation promotes pyruvate kinase M2 (PKM2) phosphorylation, initiating a positive feedback loop that involves PKM2 nuclear translocation, NF-κB activation, and oxidative stress, ultimately impairing aerobic glycolysis. Consistent with this mechanism, shikonin ameliorates podocyte injury by reducing PKM2 nuclear translocation, preventing oxidative stress and NF-κB activation, thereby restoring aerobic glycolysis.

This study utilized multisource remote sensing data and advanced technology to investigate the potential driving factors of urban heat island (UHI) effects from the perspective of local climate zones (LCZs), including natural, social, and urban three-dimensional (3-D) structural factors. Using MODIS land surface temperature remote sensing data products and supplementary datasets, the simplified urban-extent algorithm was employed to identify UHI areas and quantify UHI Intensity (UHII). The stepwise multiple linear regression method and SHapley Additive exPlanations-explained eXtreme gradient boosting machine learning method were then applied to attribute UHII to 15 selected driving factors across 17 LCZ types in 369 Chinese cities. The findings indicate that large UHI areas are predominantly associated with low-rise LCZ types, where compact building arrangements intensify UHII, and increased building heights exacerbate this effect. During daytime, the UHI effects are largely driven by urban 3-D structures, particularly within LCZ 1-6 areas. Conversely, at night, the UHI effect is more significantly impacted by natural environmental factors. These insights offer a robust scientific foundation for urban planners to craft LCZ-specific strategies aimed at fostering the development of sustainable cities and communities.

Abstract Background Roxadustat is an oral hypoxia inducing factor-prolyl hydroxylase inhibitor (HIF-PHI) that regulates iron metabolism in patients with chronic kidney disease (CKD) primarily by reducing hepcidin levels and mobilizing internal iron stores. More data are needed to demonstrate the efficacy of roxadustat in regulating iron metabolism in patients with peritoneal dialysis (PD) compared with erythropoiesis stimulating agents (ESAs). Methods This prospective cohort study enrolled PD patients with a mean hemoglobin level of 60–100 g/L. All subjects were randomized into two groups at a ratio of 2:1 the roxadustat group (106 cases), and the ESA group (53 cases). The primary endpoint was the change in the iron biomarker levels and the proportion of patients with absolute iron deficiency and functional iron deficiency. Results Compared with ESAs, roxadustat significantly decreased hepcidin level (difference, − 20.09 ng/mL; 95% CI, − 30.26 to − 9.92), attenuated the increase in serum soluble transferrin receptor (sTFR) level (difference, − 7.87 nmol/L; 95% CI, − 12.11 to − 3.64), and reduced the proportion of patients with functional iron deficiency (roxadustat, 11.43%; ESA, 33.33%). There was no significant difference in safety of the two groups over the duration of the study. Conclusions Compared with ESA group, roxadustat group showed significant differences in all iron biomarker levels except serum ferritin (sFt) and transferrin saturation (TSAT). These results suggest that roxadustat was superior to ESAs as a therapy for iron metabolism in PD patients. Trial registration: This study completed Chinese Clinical Trial Registration on March 4, 2022 (registration number: ChiCTR2200057231). Graphical abstract

Abstract Background Somatic embryogenesis is a major process for plant regeneration. However, cell communication and the gene regulatory network responsible for cell reprogramming during somatic embryogenesis are still largely unclear. Recent advances in single-cell technologies enable us to explore the mechanism of plant regeneration at single-cell resolution. Results We generate a high-resolution single-cell transcriptomic landscape of hypocotyl tissue from the highly regenerable cotton genotype Jin668 and the recalcitrant TM-1. We identify nine putative cell clusters and 23 cluster-specific marker genes for both cultivars. We find that the primary vascular cell is the major cell type that undergoes cell fate transition in response to external stimulation. Further developmental trajectory and gene regulatory network analysis of these cell clusters reveals that a total of 41 hormone response-related genes, including LAX2, LAX1, and LOX3, exhibit different expression patterns in the primary xylem and cambium region of Jin668 and TM-1. We also identify novel genes, including CSEF, PIS1, AFB2, ATHB2, PLC2, and PLT3, that are involved in regeneration. We demonstrate that LAX2, LAX1 and LOX3 play important roles in callus proliferation and plant regeneration by CRISPR/Cas9 editing and overexpression assay. Conclusions This study provides novel insights on the role of the regulatory network in cell fate transition and reprogramming during plant regeneration driven by somatic embryogenesis.

Objective: To investigate the clinical efficacy of beraprost sodium (BPS) in the treatment of chronic kidney disease (CKD). Methods: In this single-centre, prospective, controlled, single-blind study, 252 patients diagnosed with CKD and treated at the Affiliated Hospital of Xuzhou Medical University were enrolled from September 2018 to June 2021. All participants were randomised into three groups: the control, BPS 40 μg, and BPS 20 μg groups. Both treatment groups were administered conventional therapy for 6 months. Renal function in the three groups was measured and compared 3 and 6 months post-treatment. Results: 1. Renal function in the BPS 20 μg and BPS 40 μg groups was better than that in the control group after 3 and 6 months of treatment. 2. After 3 months of treatment, the levels of serum creatinine (P = 0.043), cystatin C (P = 0.039), and 24 h urinary total protein (P = 0.041) in the BPS 40 μg group were significantly lower than those in the BPS 20 μg group, the eGFR (P = 0.046) level was higher than that in the BPS 20 μg group, and the index improvement rate was better than that in the BPS 20 μg group (P 0.05). Conclusion: BPS improved renal function, reduced urinary protein levels, and delayed CKD progression. The clinical efficacy of BPS in the 40 μg group was faster than that in the BPS 20 μg group. The long-term use of BPS is effective in patients with CKD.

Abstract Insects pose significant challenges in cotton‐producing regions. Here, they describe a high‐throughput CRISPR/Cas9‐mediated large‐scale mutagenesis library targeting endogenous insect‐resistance‐related genes in cotton. This library targeted 502 previously identified genes using 968 sgRNAs, generated ≈2000 T0 plants and achieved 97.29% genome editing with efficient heredity, reaching upto 84.78%. Several potential resistance‐related mutants (10% of 200 lines) their identified that may contribute to cotton‐insect molecular interaction. Among these, they selected 139 and 144 lines showing decreased resistance to pest infestation and targeting major latex‐like protein 423 (GhMLP423) for in‐depth study. Overexpression of GhMLP423 enhanced insect resistance by activating the plant systemic acquired resistance (SAR) of salicylic acid (SA) and pathogenesis‐related (PR) genes. This activation is induced by an elevation of cytosolic calcium [Ca2+]cyt flux eliciting reactive oxygen species (ROS), which their demoted in GhMLP423 knockout (CR) plants. Protein‐protein interaction assays revealed that GhMLP423 interacted with a human epidermal growth factor receptor substrate15 (EPS15) protein at the cell membrane. Together, they regulated the systemically propagating waves of Ca2+ and ROS, which in turn induced SAR. Collectively, this large‐scale mutagenesis library provides an efficient strategy for functional genomics research of polyploid plant species and serves as a solid platform for genetic engineering of insect resistance.

Currently, urban heat island (UHI) has evolved beyond being a homogeneous climate and environmental issue, it has emerged as a critical threat to the sustainable development of urban environment. This study highlights substantial spatio-temporal expansions of UHIs in China between 2005 and 2020. Notably, the UHI intensity (UHII) exhibited a more pronounced increase during nighttime than daytime, with land surface temperature rises of 0.46 °C and 0.17 °C, respectively. Analysis of 48 representative cities revealed that although most cities experienced a faster UHII growth rate in new UHIs compared with pre-existing ones, the significant initial disparity hinders the new UHIs in 2010 and 2015 from catching up with the UHII of pre-existing UHIs in the short term. However, by 2025, it is projected that the daytime UHII of new UHIs in 2015 will surpass that of new UHIs in 2010 in 21 cities, while the same trend is expected in 31 cities during nighttime. Furthermore, spatial gradient analysis unveiled individual variations in UHII within different buffer rings. These findings provide valuable insights into the spatial expansion and dynamics of UHIs in China, contributing to the understanding of UHI effects. Moreover, these findings can inform urban renewal strategies aimed at mitigating UHI's adverse impacts, enhancing urban resilience, and fostering the development of sustainable and livable cities.

Heart failure with preserved ejection fraction (HFpEF) is present in nearly half of patients with heart failure. The prevalence of heart failure with normal or near-normal ejection fractions increases more rapidly than in patients with reduced ejection fractions. Angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), aldosterone antagonist, β-blocker, and calcium channel blocker have not shown significant efficacy in HFpEF clinical trials. Sacubitril/Valsartan, combined angiotensin receptor blocker (Valsartan) with neprilysin inhibitor (Sacubitril), was the first-of-its-kind angiotensin receptor-neprilysin inhibitor (ARNI) to be developed. It has shown significant efficacy on HFpEF in recent studies. It is considered that most of the current Sacubitril/Valsartan studies are still concentrated in the field of heart failure, especially heart failure with reduced ejection fraction (HFrEF). This review discusses the latest advances in cardiovascular, renal, and metabolic aspects of Sacubitril/Valsartan, mainly in HFpEF, providing more evidence for further future research on Sacubitril/Valsartan and raising issues that should be paid attention. At the same time, this review will introduce the academic consensus on Sacubitril/Valsartan in treating HFpEF in China.

Carsharing scale has been increasing rapidly with sharing economy. However, many users are reluctant to rent cars any longer due to the low-quality of interactive experience and usability, especially in terms of the dashboard design. This challenge should be urgently addressed in order to maintain the sustainable development of car-sharing industry and its environmental benefits. This study aims to investigate the relationship between users' driving activities (e.g., searching time, reading time, eye movement, heart rate) and dashboard layout. This study was conducted based on the experimental investigation among 58 respondents who were required to complete driving tasks in four types of cars with different dashboard layouts. Afterwards, a prediction model was developed to predict users heart rate (HR) based on the long short-term memory model, and logistic models were used to examine the relationship between the occurrence probability of minimum HR and dashboard reading. The results showed that the system usability of a dashboard was related to the drivers' eye movement characteristics including fixation duration, fixation times and pupil diameter. Most indicators had significant effects (p < 0.05) on the system usability score of corresponding dashboard. The long short-term memory model network (RMSE = 1.105, MAE = 0.009) was capable of predicting heart rate (HR) that happened in the process of instrument reading, which presented a periodic pattern rather than a continuous increase or decrease. It reflected that the network could better fit the non-linear and time-sequential laws of HR data. Furthermore, the probability of the lowest heart rate occurrence during the interaction with four dashboards was influenced by the average searching time, reading time and reading accuracy that were related to a specific layout. Overall, this study provided a theoretical reference for uncovering users' adaptive behaviors with the central control screen and for the optimal choice of a suitable dashboard layout in interface design.

The study analyzed the drivers’ take-over behaviors in intelligent cars when driving on urban roads and tried to find reasonable dimensions of the human-machine interface. Firstly, the main driving assistance functions in the process of take-over were analyzed based on the entropy theory, and the weight values of each function for the consumer’s purchase intention were calculated. Secondly, we explored the perceived comfortable dimensions of the interactive components under typical interaction modes. By means of experiments using a within-subjects design, the initial population of the evolutionary computation was obtained. The evolutionary mechanism of dimensions driven by users’ perception was constructed with a genetic algorithm. After debugging the parameters of the model, we verified the rationality of the model and evolved appropriate dimensions. Finally, the validity of the evolved dimensions was proved by a controlled experiment and paired-sample t-test. The results indicated that the completion time of most take-over tasks under the HMI with the evolved dimensions was significantly shorter, which ensured the HMI could be more conducive to the take-over quality and traffic efficiency.

Abstract The gasdermin (GSDM) family has garnered significant attention for its pivotal role in immunity and disease as a key player in pyroptosis. This recently characterized class of pore-forming effector proteins is pivotal in orchestrating processes such as membrane permeabilization, pyroptosis, and the follow-up inflammatory response, which are crucial self-defense mechanisms against irritants and infections. GSDMs have been implicated in a range of diseases including, but not limited to, sepsis, viral infections, and cancer, either through involvement in pyroptosis or independently of this process. The regulation of GSDM-mediated pyroptosis is gaining recognition as a promising therapeutic strategy for the treatment of various diseases. Current strategies for inhibiting GSDMD primarily involve binding to GSDMD, blocking GSDMD cleavage or inhibiting GSDMD-N-terminal (NT) oligomerization, albeit with some off-target effects. In this review, we delve into the cutting-edge understanding of the interplay between GSDMs and pyroptosis, elucidate the activation mechanisms of GSDMs, explore their associations with a range of diseases, and discuss recent advancements and potential strategies for developing GSDMD inhibitors.

IntroductionThe prevalence of thyroid nodules and malignancies in the elderly is a growing concern. Thyroid nodules in this population have unique characteristics, requiring careful treatment strategies that balance risks and benefits. Oncocytic carcinoma of the thyroid (OCA) is a rare, aggressive subtype with diagnostic challenges.MethodsThis case features an 84-year-old patient who presented with a neck mass and symptoms of asphyxia. Clinical evaluation, imaging studies, and biopsy were conducted to assess the nature of the thyroid lesion. Molecular testing, including genetic analysis, was performed to identify specific mutations associated with OCA and guide treatment decisions.ResultsThe patient was diagnosed with oncocytic carcinoma of the thyroid. The molecular testing revealed specific genetic mutations indicative of OCA, confirming the diagnosis. The presence of these mutations guided the treatment plan, emphasizing the importance of molecular diagnostics in managing thyroid malignancies, especially in the elderly.DiscussionThis case illustrates the complexities of diagnosing and treating thyroid malignancies in the elderly. Biopsy and molecular testing provided diagnostic accuracy and informed treatment. Individualized approaches are essential for better outcomes, especially in aggressive subtypes, balancing the risks and benefits of intervention.

Kainoid synthases are key enzymes in the biosynthesis of kainoids. Kainoids, as represented by DA and KA, are a class of naturally occurring non-protein amino acids with strong neurotransmitter activity in the mammalian central nervous system. Marine algae kainoid synthases include PnDabC from diatoms, which synthesizes domoic acid (DA), and DsKabC and GfKabC from red algae, which synthesize kainic acid (KA). Elucidation of the catalytic mechanism of kainoid synthases is of great significance for the rational design of better biocatalysts to promote the industrial production of kainoids for use in new drugs. Through modeling, molecular docking, and molecular dynamics simulations, we investigated the conformational dynamics of kainoid synthases. We found that the kainoid synthase complexes showed different stability in the simulation, and the binding and catalytic processes showed significant conformational transformations of kainoid synthase. The residues involved in specific interactions with the substrate contributed to the binding energy throughout the simulation process. Binding energy, the relaxed active pocket, electrostatic potential energy of the active pocket, the number and rotation of aromatic residues interacting with substrates during catalysis, and the number and frequency of hydrogen bonds between the individual functional groups revealed the structure–activity relationships and affected the degree of promiscuity of kainoid synthases. Our research enriches the understanding of the conformational dynamics of kainoid synthases and has potential guiding significance for their rational design.

Investigating the impacts of climate change on soil desiccation in planted forests is of theoretical and practical importance for water resource management and ecological restoration in the Loess Plateau. In this study, field experiments were conducted in four planted forests (Platycladus orientalis plots) with tree ages of 5, 12, 25, and 35a (abbreviated as T5, T12, T25, and T35 plots, respectively). Based on which, Hydrus–1D models were calibrated and validated to simulate soil water dynamics under preset climate change scenarios. Then, the soil desiccation index (SDI) in different soil layers was calculated and evaluated. The results showed that under historical climate scenarios, soil desiccation levels were slight or medium in T5, T12, and T25 plots but were mainly medium or severe in T35 plots. Future warming and drying climate would greatly increase the SDI in all plots, and its impacts increased with tree ages in the upper soil layers (0–40 cm) but decreased with it in lower layers (40–100 cm). However, it only had limited influence on the responses of soil desiccation to the climate in different hydrological years. Precipitation and vapour pressure deficit dominated soil desiccation in the upper and lower layers, respectively, and both showed linear relationships (p

Rituximab is used to eliminate B cells as a chimeric monoclonal antibody directed against CD20, a B-cell antigen expressed on B cells. To explore the impact of rituximab administered before transplantation, we implemented a retrospective, monocentric study and utilized real-world data collected at our center between January 2018 and December 2020, and then followed until December 2021. Based on whether a dose of 375mg/m2 rituximab was used at least once within two weeks before transplantation, patients undergoing allo-HSCT were classified into two groups: rituximab (N=176) and non-rituximab (N=344) group. Amongst all the patients, the application of rituximab decreased EBV reactivation (P

Study region: A typical grassland (Medicago sativa plot) and a typical forest land (Robinia pseudoacacia plot) located in the semi-arid Loess Plateau, China. Study focus: Field observations and scenario simulation approaches were used to investigate the potential impact of future warming and drying climate on the whole water budget and to assess whether, how, and to what degree the highly recommended man–driven tree–to–grass conversion could alleviate the adverse impact of such climate change on soil water. New hydrological insights for the region: Differences of interception and transpiration between two plots resulted in their different soil water storage. Under the warming and drying future climate, interception and transpiration in two plots would experience significant reductions, especially transpiration, and M. sativa plot could maintain more water than R. pseudoacacia plot. When R. pseudoacacia was replaced by M. sativa, although interception would dramatically increase, the transpiration would significantly decrease, which made the soil water storage experience an insignificant change. Climate change and tree–to–grass conversion mainly exerted their influences in months with larger precipitation, and vegetation conversion would reduce monthly T/ET. Our study improves the understanding of the hydrological processes under climate change and vegetation conversion, and also provides valuable guidelines for the management of water resources and the restoration of ecological environment in the semi–arid Loess Plateau.

Along with China's national strategy "One Belt, One Road," an increasing number of Chinese construction companies has ventured or will venture into the global market. The choice of entry mode is crucial for companies when going abroad. The objectives of this study are to (1) establish a systematic classification of the entry modes used in the international engineering field, and (2) identify and analyze the factors that influence the entry-mode choices of Chinese international construction companies (ICCs). Based on a literature review and a survey of 264 cases, a two-dimensional (2D) taxonomy model of the entry modes was established, and six factors significantly impact the choice of entry mode for Chinese ICCs were identified. The findings may help Chinese ICCs learn more about the choices available to them, the factors that influence these choices, and the way these factors influence their choices when venturing abroad. [ABSTRACT FROM AUTHOR]

In recent years, there have been concerns raised about construction industrialization in China, which have initiated a wave of policy change in both governmental and industrial organizations in order to change the mode of conventional construction. However, the current development level of regional construction industrialization (RCI) in China has not been well-characterized. This study screened preliminary index systems in five dimensions: technical, economic, sustainable, enterprise development and development environment. Based on the data gathered from the questionnaire surveys and subsequently analyzed, twenty-two critical evaluation indicators were identified. Analytic Hierarchy Process (AHP) was then employed to determine the weighting of each indicator. The evaluation method of the development level was formulated on the basis of the evaluation criteria. Jiangsu Province was used as an example in this study, with the development level of this province being comprehensively examined using a combination of the index system and evaluation method. The results show that Jiangsu has a relatively high RCI development level. The data from analysis scores of five dimensions and twenty-two indicators show that the index system is feasible, with evaluation results being consistent with actual practice. These findings provide a good practical reference for making decisions about how best to guide the development of RCI. [ABSTRACT FROM AUTHOR]

Abstract Background Lymph node metastasis (LNM) occurs frequently in young papillary thyroid carcinoma (PTC) patients, though the mortality rates are low. We aimed to analyze the relationship between age at diagnosis and LNM in PTC at a population level to elucidate the clinical behavior of PTC. Methods Data of adult patients with surgically treated PTC and follicular thyroid carcinoma (FTC) were identified from the Surveillance, Epidemiology, and End Results (SEER) database (2004–2015) to investigate the relationship between age and clinical characteristics by curve estimation. The adjusted odds ratio of age and LNM rate were determined. Results A total of 50,347 PTC (48,166) and FTC (2181) (median age: 45 and 50 years, respectively) patients met the inclusion criteria; 44.5% of those with PTC (21,428) had LNM. Rank-sum test analysis indicated differences in distribution of age in LNM-positive and LNM-negative PTC. The relationship between age, tumor size and LNM showed a quadratic curve in PTC. The mean tumor diameter and LNM rate correlated linearly with age in 18–59-year-old patients. LNM rate decreased with age (R 2 = 0.932, P

Abstract A high‐throughput non‐viral intracellular delivery platform is introduced for the transfection of large cargos with dosage‐control. This platform, termed Acoustic‐Electric Shear Orbiting Poration (AESOP), optimizes the delivery of intended cargo sizes with poration of the cell membranes via mechanical shear followed by the modulated expansion of these nanopores via electric field. Furthermore, AESOP utilizes acoustic microstreaming vortices wherein up to millions of cells are trapped and mixed uniformly with exogenous cargos, enabling the delivery of cargos into cells with targeted dosages. Intracellular delivery of a wide range of molecule sizes (90%), cell viability (>80%), and uniform dosages (

Objective: To study the characteristics of the T cell receptor (TCR) repertoire in cancer tissue, peripheral blood and regional lymph nodes (LNs) from patients with papillary thyroid carcinoma (PTC).Methods: PTC tissue, peripheral blood mononuclear cells (PBMCs) and regional LNs of six patients with papillary thyroid carcinoma were harvested. T cell receptor beta-chain (TCRβ) profiling was performed though high-throughput sequencing (HTS), and IMonitor, MiXCR and VDJtools were used to analyze the characteristics of the TCR repertoire.Results: The results of IMonitor and those of MiXCR and VDJtools were very similar. The unique CDR3 of TCRβ from LNs was higher than that of PBMCs, and the CDR3 of TCRβ from LNs was higher than that of PTC tissue. Shannon's diversity index, D50, inverse Simpson index_mean and normalized Shannon's diversity index_mean of CDR3 from LNs were higher than those of PTCs and PBMCs. The HEC (high expansion clones) rate of CDR3 sequences at the amino acid level in PTC tissue was higher than that of PBMCs, which was higher than that of LNs. The V-J HEC rate of CDR3 was highest in PTC tissue, followed by PBMCs and LNs.Conclusion: TCR CDR3 profiling showed differences among and within the PBMCs, PTC tissues and regional LNs of PTC, including unique CDR3, CDR3 HEC at the amino acid level, CDR3 V-J HEC at the amino acid level, Shannon's diversity index and D50. The TCRβ repertoire of PTC tissue, peripheral blood and regional LNs of PTC provide a reference for further study of immunity mechanisms against PTC.

Background: Streptococcus equi ssp. zooepidemicus (S. zooepidemicus) is an important pathogen causing swine streptococcosis in China. Pathogenicity islands (PAIs) of S. zooepidemicus have been transferred among bacteria through horizontal gene transfer (HGT) and play important roles in the adaptation and increased virulence of S. zooepidemicus. The present study used comparative genomics to examine the different pathogenicities of S. zooepidemicus. Results: Genome of S. zooepidemicus ATCC35246 (Sz35246) comprises 2,167,264-bp of a single circular chromosome, with a GC content of 41.65%. Comparative genome analysis of Sz35246, S. zooepidemicus MGCS10565 (Sz10565), Streptococcus equi. ssp. equi. 4047 (Se4047) and S. zooepidemicus H70 (Sz70) identified 320 Sz35246- specific genes, clustered into three toxin-antitoxin (TA) systems PAIs and one restriction modification system (RM system) PAI. These four acquired PAIs encode proteins that may contribute to the overall pathogenic capacity and fitness of this bacterium to adapt to different hosts. Analysis of the in vivo and in vitro transcriptomes of this bacterium revealed differentially expressed PAI genes and non-PAI genes, suggesting that Sz35246 possess mechanisms for infecting animals and adapting to a wide range of host environments. Analysis of the genome identified potential Sz35246 virulence genes. Genes of the Fim III operon were presumed to be involved in breaking the host-restriction of Sz35246. Conclusion: Genome wide comparisons of Sz35246 with three other strains and transcriptome analysis revealed novel genes related to bacterial virulence and breaking the host-restriction. Four specific PAIs, which were judged to have been transferred into Sz35246 genome through HGT, were identified for the first time. Further analysis of the TA and RM systems in the PAIs will improve our understanding of the pathogenicity of this bacterium and could lead to the development of diagnostics and vaccines. [ABSTRACT FROM AUTHOR]