Comprehensive analysis of INTS family related to expression, prognosis, diagnosis and immune features in hepatocellular carcinoma.

Purpose: The integrator subunit (INTS) family, a group exclusive to metazoans, participates in various biologic processes. However, their roles in hepatocellular carcinoma (HCC) remain largely unexplored. Methods: Public databases were utilized to investigate the transcriptional and protein expression, and clinical relevance of the INTS family in HCC. Meanwhile, the effects of INTS13 knockdown and overexpression on cell proliferation and apoptosis were studied using HCC cell lines. Results: The mRNA expression of most INTSs were higher in tumor than normal tissues. Higher expression of INTS1/2/3/4/7/8/9/11/12/13 were correlated with poorer overall survival (OS) in Kaplan-Meier Survival Analysis. Multivariate analysis revealed higher level of INTS13 was an independent prognostic factor for shorter OS. Furthermore, genetic alteration of INTS3/6/7/8/9/10 were found in HCC patients and was associated with shorter disease-free survival and progression-free survival. INTS1/2/3/5/7/11/13/14 were associated with activation of tumor-induced immune response and immune infiltration in HCC. Knockdown of INTS13 inhibited cell proliferation and induced apoptosis in HCC cell lines, while overexpression of INTS13 had the opposite effect. Conclusion: Our results indicate that INTS13 is an independent prognostic biomarker in HCC. Furthermore, INTS13 enhances cell proliferation and decreases cell apoptosis in HCC cell lines leading to a poorer OS in HCC patients.

Black soldier fly larvae bioconversion and subsequent composting promote larval frass quality during pig and chicken manure transformation process.

This research systematically assessed the changes in carbon, nitrogen and microbial profiling during pig and chicken manure transformation by black soldier fly larvae (BSFL) and subsequent composting process. BSFL had higher conversion efficiency for chicken manure. The pH, phosphorus and potassium contents in fresh BSFL frass increased than raw manure, but conductivity, total-/nitrate-/ammonium-nitrogen decreased. After BSFL conversion, pig manure had a larger nitrogen loss (25 %) while chicken manure had a larger carbon loss (32 %). During subsequent composting, the indicator changes (e.g. humus, ammonium nitrogen) in frass composts basically remained stable after 20-30 days. Compared to natural composts, frass composts had higher humification degree, cellulase activities, and more cellulose-degrading bacteria. Subsequent composting further reduced potential pathogens (reduced by 98.9 %-99.7 % than raw manure), and elevated the aromaticity and humification of frass. The findings gave an insight into the maturation management of manure-sourced insect frass.

A novel anoikis-related signature predicts prognosis risk and treatment responsiveness in diffuse large B-cell lymphoma.

BACKGROUND: Although anoikis plays a role in cancer metastasis and aggressiveness, it has rarely been reported in diffuse large B cell lymphoma (DLBCL). METHODS: We obtained RNA sequencing data and matched clinical data from the GEO database. An anoikis-related genes (ARGs)-based risk signature was developed in GSE10846 training cohort and validated in three other cohorts. Additionally, we predicted half-maximal inhibitory concentration (IC50) of drugs based on bioinformatics method and obtained the actual IC50 to some chemotherapy drugs via cytotoxicity assay. RESULTS: The high-risk group, as determined by our signature, was associated with worse prognosis and an immunosuppressive environment in DLBCL. Meanwhile, the nomogram based on eight variables had more accurate ability in forecasting the prognosis than the international prognostic index in DLBCL. The prediction of IC50 indicated that DLBCL patients in the high-risk group were more sensitive to doxorubicin, IPA-3, lenalidomide, gemcitabine, and CEP.701, while patients in the low-risk group were sensitive to cisplatin and dasatinib. Consistent with the prediction, cytotoxicity assay suggested the higher sensitivity to doxorubicin and gemcitabine and the lower sensitivity to dasatinib in the high-risk group in DLBCL. CONCLUSION: The ARG-based signature may provide a promising direction for prognosis prediction and treatment optimization for DLBCL patients.

Downregulation of RCN1 inhibits esophageal squamous cell carcinoma progression and M2 macrophage polarization.

Reticulocalbin 1 (RCN1) is a calcium-binding protein involved in the regulation of calcium homeostasis in the endoplasmic reticulum. The aim of this study was to explore the clinical value and biological role of RCN1 in esophageal squamous cell carcinoma (ESCC). In addition, we investigated the effect of RCN1 on the polarization of tumor-associated macrophages (TAMs). The GSE53625 dataset from the Gene Expression Omnibus database was used to analyze the expression of RCN1 mRNA and its relationship with clinical value and immune cell infiltration. Immunohistochemistry was used to validate the expression of RCN1 and its correlation with clinicopathological characteristics. Subsequently, transwell and cell scratch assays were conducted to evaluate the migration and invasion abilities of ESCC cells. The expression levels of epithelial-mesenchymal transition (EMT)-related proteins were evaluated by western blot, while apoptosis was detected by flow cytometry and western blot. Additionally, qRT‒PCR was utilized to evaluate the role of RCN1 in macrophage polarization. RCN1 was significantly upregulated in ESCC tissues and was closely associated with lymphatic metastasis and a poor prognosis, and was an independent prognostic factor for ESCC in patients. Knockdown of RCN1 significantly inhibited the migration, invasion, and EMT of ESCC cells, and promoted cell apoptosis. In addition, RCN1 downregulation inhibited M2 polarization. RCN1 is upregulated in ESCC patients and is negatively correlated with patient prognosis. Knocking down RCN1 inhibits ESCC progression and M2 polarization. RCN1 can serve as a potential diagnostic and prognostic indicator for ESCC, and targeting RCN1 is a very promising therapeutic strategy.

DDX58 variant triggers IFN-ß-induced autophagy in trabecular meshwork and influences intraocular pressure.

Singleton-Merten syndrome (SMS) is a rare immunogenetic disorder affecting multiple systems, characterized by dental dysplasia, aortic calcification, glaucoma, skeletal abnormalities, and psoriasis. Glaucoma, a key feature of both classical and atypical SMS, remains poorly understood in terms of its molecular mechanism caused by DDX58 mutation. This study presented a novel DDX58 variant (c.1649A>C [p.Asp550Ala]) in a family with childhood glaucoma. Functional analysis showed that DDX58 variant caused an increase in IFN-stimulated gene expression and high IFN-ß-based type-I IFN. As the trabecular meshwork (TM) is responsible for controlling intraocular pressure (IOP), we examine the effect of IFN-ß on TM cells. Our study is the first to demonstrate that IFN-ß significantly reduced TM cell viability and function by activating autophagy. In addition, anterior chamber injection of IFN-ß remarkably increased IOP level in mice, which can be attenuated by treatments with autophagy inhibitor chloroquine. To uncover the specific mechanism underlying IFN-ß-induced autophagy in TM cells, we performed microarray analysis in IFN-ß-treated and DDX58 p.Asp550Ala TM cells. It showed that RSAD2 is necessary for IFN-ß-induced autophagy. Knockdown of RSAD2 by siRNA significantly decreased autophagy flux induced by IFN-ß. Our findings suggest that DDX58 mutation leads to the overproduction of IFN-ß, which elevates IOP by modulating autophagy through RSAD2 in TM cells.

Tibetan Mesenchymal Stem Cell-derived Exosomes Alleviate Pulmonary Vascular Remodeling in Hypoxic Pulmonary Hypertension Rats.

Hypoxic pulmonary hypertension (HPH) is characterized by progressive pulmonary vasoconstriction, vascular remodeling, and right ventricular hypertrophy, causing right heart failure. This study aimed to investigate the therapeutic effects of exosomes from Tibetan umbilical cord mesenchymal stem cells on HPH via the TGF-ß1/Smad2/3 pathway, comparing them with exosomes from Han Chinese individuals. An HPH rat model was established in vivo, and a hypoxia-induced injury in the rat pulmonary artery smooth muscle cells (rPASMCs) was simulated in vitro. Exosomes from human umbilical cord mesenchymal stem cells were administered to HPH model rats or added to cultured rPASMCs. The therapeutic effects of Tibetan-mesenchymal stem cell-derived exosomes (Tibetan-MSC-exo) and Han-mesenchymal stem cell-derived exosomes (Han-MSC-exo) on HPH were investigated through immunohistochemistry, Western blotting, EdU, and Transwell assays. The results showed that Tibetan-MSC-exo significantly attenuated pulmonary vascular remodeling and right ventricular hypertrophy in HPH rats compared with Han-MSC-exo. Tibetan-MSC-exo demonstrated better inhibition of hypoxia-induced rPASMCs proliferation and migration. Transcriptome sequencing revealed upregulated genes (Nbl1, Id2, Smad6, and Ltbp1) related to the TGFß pathway. Nbl1 knockdown enhanced hypoxia-induced rPASMCs proliferation and migration, reversing Tibetan-MSC-exo-induced downregulation of TGFß1 and p-Smad2/3. Furthermore, TGFß1 overexpression hindered the therapeutic effects of Tibetan-MSC-exo and Han-MSC-exo on hypoxic injury. These findings suggest that Tibetan-MSC-exo favors HPH treatment better than Han-MSC-exo, possibly through the modulation of the TGFß1/Smad2/3 pathway via Nbl1.

Droplet Energy Harvesting System Based on Total-Current Nanogenerator.

The droplet-based nanogenerator (DNG) is a highly promising technology for harvesting high-entropy water energy in the era of the Internet of Things. Yet, despite the exciting progress made in recent years, challenges have emerged unexpectedly for the AC-type DNG-based energy system as it transitions from laboratory demonstrations to real-world applications. In this work, we propose a high-performance DNG system based on the total-current nanogenerator concept to address these challenges. This system utilizes the water-charge-shuttle architecture for easy scale-up, employs the field effect to boost charge density of the triboelectric layer, adopts an on-solar-panel design to improve compatibility with solar energy, and is equipped with a novel DC-DC buck converter as power management circuit. These features allow the proposed system to overcome the existing bottlenecks of DNG and empower the system with superior performances compared with previous ones. Notably, with the core architecture measuring only 15 cm × 12.5 cm × 0.3 cm in physical dimensions, this system reaches a record-high open-circuit voltage of 4200 V, capable of illuminating 1440 LEDs, and can charge a 4.7 mF capacitor to 4.5 V in less than 24 min. In addition, the practical potential of the proposed DNG system is further demonstrated through a self-powered, smart greenhouse application scenario. These demonstrations include the continuous operation of a thermohygrometer, the operation of a Bluetooth plant monitor, and the all-weather energy harvesting capability. This work will provide valuable inspiration and guidance for the systematic design of next-generation DNG to unlock the sustainable potential of distributed water energy for real-world applications.

Elevated circulating BMP9 aggravates pulmonary angiogenesis in hepatopulmonary syndrome rats through ALK1-Endoglin-Smad1/5/9 signalling.

BACKGROUND: Bone morphogenetic protein 9 (BMP9) is a hepatokine that plays a pivotal role in the progression of liver diseases. Moreover, an increasing number of studies have shown that BMP9 is associated with hepatopulmonary syndrome (HPS), but its role in HPS is unclear. Here, we evaluated the influence of CBDL on BMP9 expression and investigated potential mechanisms of BMP9 signalling in HPS. METHODS: We profiled the circulating BMP9 levels in common bile duct ligation-induced HPS rat model, and then investigated the effects and mechanisms of HPS rat serum on pulmonary vascular endothelial dysfunction in rat model, as well as in primarily cultured rat pulmonary microvascular endothelial cells. RESULTS: Our data revealed that circulating BMP9 levels were significantly increased in the HPS rats compared to control group. Besides, the elevated BMP9 in HPS rat serum was not only crucial for promoting endothelial cell proliferation and tube formation through the activin receptor-like kinase1 (ALK1)-Endoglin-Smad1/5/9 pathway, but also important for accumulation of monocytes. Treatments with ALK1-Fc or silencing ALK1 expression to inhibit the BMP9 signalling pathway effectively eliminated these effects. In agreement with these observations, increased circulating BMP9 was associated with an increase in lung vessel density and accumulation of pro-angiogenic monocytes in the microvasculature in HPS rats. CONCLUSIONS: This study provided evidence that elevated circulating BMP9, secreted from the liver, promote pulmonary angiogenesis in HPS rats via ALK1-Endoglin-Smad1/5/9 pathway. In addition, BMP9-regulated pathways are also involved in accumulation of pro-angiogenic monocytes in the pulmonary microvasculature in HPS rats.

Different effects of TCBPA exposure on liver cancer cells and liver cells: two sides of the coin.

Tetrachlorobisphenol A (TCBPA), widely used as a substitute for tetrabromobisphenol A (TBBPA), has been detected in various environmental media. Therefore, a detailed evaluation of the toxicological properties of TCBPA is necessary. In this study, we used hepatoma and normal liver cell models in vitro to investigate the effects of TCBPA. Our findings indicate that TCBPA promotes the proliferation of liver cancer cells, as evidenced by MTT and EdU assays, and enhances the expression levels of molecules related to hepatoma proliferation. Further investigation into the molecular mechanism revealed that TCBPA-induced hepatoma proliferation is regulated by an NLRP3-mediated inflammatory process. Additionally, TCBPA was found to promote the epithelial-mesenchymal transition (EMT) process in liver cancer cells. Conversely, TCBPA inhibited the proliferation of normal liver cells. Mechanistic studies showed that TCBPA induced cell pyroptosis in normal liver cells by evaluating a series of related markers, including NLRP3, IL-1ß, ASC, GASDMD, and Caspase 1. In vivo models further showed that TCBPA causes liver tissue damage. In summary, this study demonstrates that TCBPA has a dual effect: promoting the occurrence and development of liver tumor cells in vitro, while inhibiting the proliferation of normal liver cells, like two sides of a coin. These opposite cellular outcomes are regulated by NLRP3-mediated inflammatory processes, providing valuable insights for evaluating the potential health impacts of TCBPA.

An effective strategy for assembling the sex-limited chromosome.

BACKGROUND: Most currently available reference genomes lack the sequence map of sex-limited (such as Y and W) chromosomes, which results in incomplete assemblies that hinder further research on sex chromosomes. Recent advancements in long-read sequencing and population sequencing have provided the opportunity to assemble sex-limited chromosomes without the traditional complicated experimental efforts. FINDINGS: We introduce the first computational method, Sorting long Reads of Y or other sex-limited chromosome (SRY), which achieves improved assembly results compared to flow sorting. Specifically, SRY outperforms in the heterochromatic region and demonstrates comparable performance in other regions. Furthermore, SRY enhances the capabilities of the hybrid assembly software, resulting in improved continuity and accuracy. CONCLUSIONS: Our method enables true complete genome assembly and facilitates downstream research of sex-limited chromosomes.

A general pattern of plant traits and their relationships with environmental factors and microbial life-history strategies.

The trait-based unidimensional plant economics spectrum provides a valuable framework for understanding plant adaptation strategies to the environment. However, it is still uncertain whether there is a general multidimensionality of how variation of both leaf and fine root traits are influenced by environmental factors, and how these relate to microbial resource strategies. Here, we examined the coordination patterns of four pairs of similar leaf and fine root traits of herbaceous plants in an alpine meadow at the community-level, and their environmental driving patterns. We then assessed their correlation with microbial life-history strategies, as these exhibit analogous resource strategies with plants in terms of growth and resource utilization efficiency. Results exhibited an analogous multidimensionality of the economics spectrum for leaf and fine root traits: the first dimension, collaboration gradient, primarily represented a tradeoff between lifespan and resource foraging efficiency; the second dimension, conservation gradient, primarily represented a tradeoff between conservation and acquisition in resource uptake. Climate variables had a stronger impact on both dimensions for leaf and fine root traits than soil variables did; whereas, the primary drivers were more complex for fine root traits than for leaf traits. The collaboration gradient of leaf and fine root traits exhibited consistent relationships with soil microbial life-history strategies, both showed negative and positive correlation with bacterial and fungal strategies, respectively. Our findings suggest that both leaves and fine roots have general multidimensional strategies for adapting to new environments and provide a solid basis for further understanding the relationships between the adaptive strategies of plants and microbes.

Contemporary strategies and approaches for characterizing composition and enhancing biofilm penetration targeting bacterial extracellular polymeric substances.

Extracellular polymeric substances (EPS) constitutes crucial elements within bacterial biofilms, facilitating accelerated antimicrobial resistance and conferring defense against the host's immune cells. Developing precise and effective antibiofilm approaches and strategies, tailored to the specific characteristics of EPS composition, can offer valuable insights for the creation of novel antimicrobial drugs. This, in turn, holds the potential to mitigate the alarming issue of bacterial drug resistance. Current analysis of EPS compositions relies heavily on colorimetric approaches with a significant bias, which is likely due to the selection of a standard compound and the cross-interference of various EPS compounds. Considering the pivotal role of EPS in biofilm functionality, it is imperative for EPS research to delve deeper into the analysis of intricate compositions, moving beyond the current focus on polymeric materials. This necessitates a shift from heavy reliance on colorimetric analytic methods to more comprehensive and nuanced analytical approaches. In this study, we have provided a comprehensive summary of existing analytical methods utilized in the characterization of EPS compositions. Additionally, novel strategies aimed at targeting EPS to enhance biofilm penetration were explored, with a specific focus on highlighting the limitations associated with colorimetric methods. Furthermore, we have outlined the challenges faced in identifying additional components of EPS and propose a prospective research plan to address these challenges. This review has the potential to guide future researchers in the search for novel compounds capable of suppressing EPS, thereby inhibiting biofilm formation. This insight opens up a new avenue for exploration within this research domain.

Basal actomyosin pulses expand epithelium coordinating cell flattening and tissue elongation.

Actomyosin networks constrict cell area and junctions to alter cell and tissue shape. However, during cell expansion under mechanical stress, actomyosin networks are strengthened and polarized to relax stress. Thus, cells face a conflicting situation between the enhanced actomyosin contractile properties and the expansion behaviour of the cell or tissue. To address this paradoxical situation, we study late Drosophila oogenesis and reveal an unusual epithelial expansion wave behaviour. Mechanistically, Rac1 and Rho1 integrate basal pulsatile actomyosin networks with ruffles and focal adhesions to increase and then stabilize basal area of epithelial cells allowing their flattening and elongation. This epithelial expansion behaviour bridges cell changes to oocyte growth and extension, while oocyte growth in turn deforms the epithelium to drive cell spreading. Basal pulsatile actomyosin networks exhibit non-contractile mechanics, non-linear structures and F-actin/Myosin-II spatiotemporal signal separation, implicating unreported expanding properties. Biophysical modelling incorporating these expanding properties well simulates epithelial cell expansion waves. Our work thus highlights actomyosin expanding properties as a key mechanism driving tissue morphogenesis.

Activation of farnesoid X receptor enhances the efficacy of normothermic machine perfusion in ameliorating liver ischemia-reperfusion injury.

The shortage of transplant organs remains a severe global issue. Normothermic machine perfusion (NMP) has the potential to increase organ availability, yet its efficacy is hampered by the inflammatory response during machine perfusion. Mouse liver ischemia-reperfusion injury (IRI) models, discarded human liver models, and porcine marginal liver transplantation models were utilized to investigate whether farnesoid X receptor (FXR) activation could mitigate inflammation-induced liver damage. FXR expression levels before and after reperfusion were measured. Gene editing and coimmunoprecipitation techniques were employed to explore the regulatory mechanism of FXR in inflammation inhibition. The expression of FXR correlates with the extent of liver damage after reperfusion. Activation of FXR significantly suppressed the inflammatory response triggered by IRI, diminished the release of proinflammatory cytokines, and improved liver function recovery during NMP, assisting discarded human livers to reach transplant standards. Mechanistically, FXR disrupts the interaction between p65 and p300, thus inhibiting modulating the nuclear factor kappa-B signaling pathway, a key instigator of inflammation. Our research across multiple species confirms that activating FXR can optimize NMP by attenuating IRI-related liver damage, thereby improving the utilization of marginal livers for transplantation.

Study of the changes in the microstructures and properties of grease using ball milling to simulate a bearing shear zone on grease.

The effects of shear degradation on the microstructures and properties of grease were investigated using a planetary ball mill to simulate a bearing shear zone on grease. The microstructure, cone penetration, colloidal stability, rheological properties noise properties, water washout characteristics and low-temperature torque of lithium grease were characterized. The microstructure of the initial lithium grease is a three-dimensional network structure formed by the uniform fibers. The entanglement level is high. As the ball milling shear time increases, the network structure of lithium grease is destroyed and the fibers are sheared to become short. Eventually all of them become short fibers. The performance test of lithium grease reveal that the cone penetration increases, colloidal stability, structural strength, noise properties, water washout characteristics of lithium grease gradually decreased with the increase of ball milling shear time. Additionally, the low-temperature starting torque and running torque of the grease gradually decrease. This phenomenon occurs due to changes in the microstructure of lithium grease. The shear degradation of lithium grease was mainly divided into two stages: the rapid stage was the destruction of the thickener network structure and the fibers being shortened by shearing. The slow stage was the process in which short fibers were sheared into shorter fibers.

Generation and characterization of the iPS cell line (SYSUSHi001-A) derived from the peripheral blood mononuclear cells (PBMCs) of a 33-year-old patient with acute myeloid leukemia (AML).

We successfully developed an induced pluripotent stem cell (iPSC) line, SYSUSHi001-A, from the peripheral blood mononuclear cells (PBMC) of a patient with Acute Myeloid Leukemia, harboring two genetic mutations (XPO1: c.591-4_591-3dupTT; PALB2: c.3296C > T; p.T1099M). This iPSC line was facilitated through the use of episomal plasmids encoding OCT4, SOX2, KLF4, L-MYC, and human miR-302. The SYSUSHi001-A iPSC line exhibited characteristic embryonic stem cell-like morphology, maintained the XPO1 and PALB2 mutations, expressed key pluripotency markers, preserved a normal karyotype (46, XY), and demonstrated the ability to differentiate into cells from all three germ layers in vitro.

Deciphering and predicting changes in antibiotic resistance genes during pig manure aerobic composting via machine learning model.

Livestock manure is one of the most important pools of antibiotic resistance genes (ARGs) in the environment. Aerobic composting can effectively reduce the spread of antibiotic resistance risk in livestock manure. Understanding the effect of aerobic composting process parameters on manure-sourced ARGs is important to control their spreading risk. In this study, the effects of process parameters on ARGs during aerobic composting of pig manure were explored through data mining based on 191 valid data collected from literature. Machine learning (ML) models (XGBoost and Random Forest) were utilized to predict the rate of ARGs changes during pig manure composting. The model evaluation index of the XGBoost model (R2 = 0.651) was higher than that of the Random Forest (R2 = 0.490), indicating that XGBoost had better prediction performance. Feature importance was further calculated for the XGBoost model, and the XGBoost black box model was interpreted by Shapley additive explanations analysis. Results indicated that the influencing factors on the ARGs variation in pig manure were sequentially divided into thermophilic period, total composting period, composting real time, and thermophilic stage average temperature. The findings gave an insight into the application of ML models to predict and decipher the ARG changes during manure composting and provided suggestions for better composting manipulation and optimization of process parameters.

5G Indoor Positioning Error Correction Based on 5G-PECNN.

With the development of the mobile network communication industry, 5G has been widely used in the consumer market, and the application of 5G technology for indoor positioning has emerged. Like most indoor positioning techniques, the propagation of 5G signals in indoor spaces is affected by noise, multipath propagation interference, installation errors, and other factors, leading to errors in 5G indoor positioning. This paper aims to address these issues by first constructing a 5G indoor positioning dataset and analyzing the characteristics of 5G positioning errors. Subsequently, we propose a 5G Positioning Error Correction Neural Network (5G-PECNN) based on neural networks. This network employs a multi-level fusion network structure designed to adapt to the error characteristics of 5G through adaptive gradient descent. Experimental validation demonstrates that the algorithm proposed in this paper achieves superior error correction within the error region, significantly outperforming traditional neural networks.

Genomic insights into the origin and evolution of spelt (Triticum spelta L.) as a valuable gene pool for modern wheat breeding.

Spelt (Triticum aestivum ssp. spelta) is an important wheat subspecies mainly cultivated in Europe before the 20th century that has contributed to modern wheat breeding as a valuable genetic resource. However, relatively little is known about the origins and maintenance of spelt populations. Here, using resequencing data from 416 worldwide wheat accessions, including representative spelt wheat, we demonstrate that European spelt emerged when primitive hexaploid wheat spread to the west and hybridized with pre-settled domesticated emmer, the putative maternal donor. Genomic introgression regions from domesticated emmer confer spelt's primitive morphological characters used for species taxonomy, such as tenacious glumes and later flowering. We propose a haplotype-based "spelt index" to identify spelt-type wheat varieties and to quantify utilization of the spelt gene pool in modern wheat cultivars. This study reveals the genetic basis for the establishment of the spelt wheat subspecies in a specific ecological niche and the vital role of the spelt gene pool as a unique germplasm resource in modern wheat breeding.

Comparison of the safety and efficacy of the wild-type and lpxL/lpxM mutant inactivated vaccine against the avian pathogenic Escherichia coli O1, O2, and O78 challenge.

Avian pathogenic Escherichia coli (APEC) is primarily responsible for causing septicemia, pneumonitis, peritonitis, swollen head syndrome, and salpingitis in poultry, leading to significant losses in the poultry sector, particularly within the broiler industry. The removal of the lpxL and lpxM genes led to an eightfold decrease in the endotoxin levels of wild APEC strains. In this study, mutant strains of lpxL/lpxM and their O1, O2, and O78 wild-type strains were developed for an inactivated vaccine (referred to as the mutant vaccine and the wild-type vaccine, respectively), and the safety and effectiveness of these two prototype vaccines were assessed in white Leghorn chickens. Findings indicated that chickens immunized with the mutant vaccine showed a return of appetite sooner post-immunization and experienced earlier disappearance of nodules at the injection site compared to those immunized with the wild-type vaccine. Pathological examinations revealed that lesions were still present in the liver, lung, and injection site in chickens vaccinated with the wild-type vaccine 14 days post-vaccination (dpv), whereas no lesions were found in chickens vaccinated with the mutant vaccine at 14 dpv. There were no significant differences in antibody levels on the challenge day or in mortality or lesion scores between challenged birds immunized with either the mutant vaccine or the wild-type vaccine at the same dose. In this study, the safety of a single dose or overdose of the mutant vaccine and its efficacy at one dose were evaluated in broilers, and the results showed that the mutant vaccine had no adverse effects on or protected vaccinated broilers from challenge with the APEC O1, O2, or O78 strains. These results demonstrated that the mutant polyvalent inactivated vaccine is a competitive candidate against APEC O1, O2, and O78 infection compared to the wild-type vaccine.