Efficient identification of QTL for agronomic traits in foxtail millet (Setaria italica) using RTM- and MLM-GWAS.

KEY MESSAGE: Eleven QTLs for agronomic traits were identified by RTM- and MLM-GWAS, putative candidate genes were predicted and two markers for grain weight were developed and validated. Foxtail millet (Setaria italica), the second most cultivated millet crop after pearl millet, is an important grain crop in arid regions. Seven agronomic traits of 408 diverse foxtail millet accessions from 15 provinces in China were evaluated in three environments. They were clustered into two divergent groups based on genotypic data using ADMIXTURE, which was highly consistent with their geographical distribution. Two models for genome-wide association studies (GWAS), namely restricted two-stage multi-locus multi-allele (RTM)-GWAS and mixed linear model (MLM)-GWAS, were used to dissect the genetic architecture of the agronomic traits based on 13,723 SNPs. Eleven quantitative trait loci (QTLs) for seven traits were identified using two models (RTM- and MLM-GWAS). Among them, five were considered stable QTLs that were identified in at least two environments using MLM-GWAS. One putative candidate gene (SETIT_006045mg, Chr4: 744,701-746,852) that can enhance grain weight per panicle was identified based on homologous gene comparison and gene expression analysis and was validated by haplotype analysis of 330 accessions with high-depth (10×) resequencing data (unpublished). In addition, homologous gene comparison and haplotype analysis identified one putative foxtail millet ortholog (SETIT_032906mg, Chr2: 5,020,600-5,029,771) with rice affecting the target traits. Two markers (cGWP6045 and kTGW2906) were developed and validated and can be used for marker-assisted selection of foxtail millet with high grain weight. The results provide a fundamental resource for foxtail millet genetic research and breeding and demonstrate the power of integrating RTM- and MLM-GWAS approaches as a complementary strategy for investigating complex traits in foxtail millet.

Correlation between the changes of brain amplitude of low-frequency fluctuation and cognitive impairment in patients with neuropsychiatric lupus.

PURPOSE: To explore the relationship between brain function changes and clinical serological indicators and behavioral cognitive assessment in patients with neuropsychiatric systemic lupus erythematosus (NPSLE), and understand the pathogenesis of NPSLE from the perspective of imaging. METHODS: The resting-state functional imaging data, clinical serological, and behavioral cognitive assessment scores of 28 patients with NPSLE and 22 healthy controls (HC) were prospectively collected. The resting-state amplitude of low-frequency fluctuation (ALFF) values obtained from the analysis and processing were correlated with the serological data and behavioral cognitive assessment scores to determine the relationship between these data. RESULTS: The average age of the patients of the NPSLE group was older than that of the HC group; significant differences in education level, Auditory Verbal Learning Test Hua Shan Version (AVLT-H), and Trail Making Test scores were observed between the two groups. The NPSLE group demonstrated increased brain activity in the insula, precentral gyrus, and superior temporal gyrus, and decreased brain activity in the superior parietal gyrus. The ALFF value of the insula positively correlated with the Anti-ß2gp1 antibody and negatively correlated with the anti-nucleosome antibody and the AVL-recall (RC) score. The ALFF of the precentral gyrus negatively correlated with the AVL-immediate recall (I). The ALFF value of the superior temporal gyrus negatively correlated with the AVL-RC score. The left superior parietal gyrus positively correlated with the c-reactive protein. The right superior parietal gyrus positively correlated with the System Lupus Erythematosus Disease Activity Index and negatively correlated with the AVL-I score. CONCLUSION: Patients with NPSLE show different brain activity changes in different brain regions, and the abnormal brain regions are correlated with certain lupus antibodies, inflammatory factors, and cognitive assessment, thereby suggesting that the correlation between the three could provide novel insights into the pathogenesis of NPSLE.

Integrating GWAS and TWAS to elucidate the genetic architecture of maize leaf cuticular conductance.

The cuticle, a hydrophobic layer of cutin and waxes synthesized by plant epidermal cells, is the major barrier to water loss when stomata are closed. Dissecting the genetic architecture of natural variation for maize (Zea mays L.) leaf cuticular conductance (gc) is important for identifying genes relevant to improving crop productivity in drought-prone environments. To this end, we performed an integrated genome- and transcriptome-wide association studies (GWAS and TWAS) to identify candidate genes putatively regulating variation in leaf gc. Of the 22 plausible candidate genes identified, 4 were predicted to be involved in cuticle precursor biosynthesis and export, 2 in cell wall modification, 9 in intracellular membrane trafficking, and 7 in the regulation of cuticle development. A gene encoding an INCREASED SALT TOLERANCE1-LIKE1 (ISTL1) protein putatively involved in intracellular protein and membrane trafficking was identified in GWAS and TWAS as the strongest candidate causal gene. A set of maize nested near-isogenic lines that harbor the ISTL1 genomic region from eight donor parents were evaluated for gc, confirming the association between gc and ISTL1 in a haplotype-based association analysis. The findings of this study provide insights into the role of regulatory variation in the development of the maize leaf cuticle and will ultimately assist breeders to develop drought-tolerant maize for target environments.

Transcriptomic network analyses shed light on the regulation of cuticle development in maize leaves.

Plant cuticles are composed of wax and cutin and evolved in the land plants as a hydrophobic boundary that reduces water loss from the plant epidermis. The expanding maize adult leaf displays a dynamic, proximodistal gradient of cuticle development, from the leaf base to the tip. Laser microdissection RNA Sequencing (LM-RNAseq) was performed along this proximodistal gradient, and complementary network analyses identified potential regulators of cuticle biosynthesis and deposition. A weighted gene coexpression network (WGCN) analysis suggested a previously undescribed function for PHYTOCHROME-mediated light signaling during the regulation of cuticular wax deposition. Genetic analyses reveal that phyB1 phyB2 double mutants of maize exhibit abnormal cuticle composition, supporting the predictions of our coexpression analysis. Reverse genetic analyses also show that phy mutants of the moss Physcomitrella patens exhibit abnormal cuticle composition, suggesting an ancestral role for PHYTOCHROME-mediated, light-stimulated regulation of cuticle development during plant evolution.

Constructing functional cuticles: analysis of relationships between cuticle lipid composition, ultrastructure and water barrier function in developing adult maize leaves.

BACKGROUND AND AIMS: Prior work has examined cuticle function, composition and ultrastructure in many plant species, but much remains to be learned about how these features are related. This study aims to elucidate relationships between these features via analysis of cuticle development in adult maize (Zea mays L.) leaves, while also providing the most comprehensive investigation to date of the composition and ultrastructure of adult leaf cuticles in this important crop plant. METHODS: We examined water permeability, wax and cutin composition via gas chromatography, and ultrastructure via transmission electron microscopy, along the developmental gradient of partially expanded adult maize leaves, and analysed the relationships between these features. KEY RESULTS: The water barrier property of the adult maize leaf cuticle is acquired at the cessation of cell expansion. Wax types and chain lengths accumulate asynchronously over the course of development, while overall wax load does not vary. Cutin begins to accumulate prior to establishment of the water barrier and continues thereafter. Ultrastructurally, pavement cell cuticles consist of an epicuticular layer, and a thin cuticle proper that acquires an inner, osmiophilic layer during development. CONCLUSIONS: Cuticular waxes of the adult maize leaf are dominated by alkanes and alkyl esters. Unexpectedly, these are localized mainly in the epicuticular layer. Establishment of the water barrier during development coincides with a switch from alkanes to esters as the major wax type, and the emergence of an osmiophilic (likely cutin-rich) layer of the cuticle proper. Thus, alkyl esters and the deposition of the cutin polyester are implicated as key components of the water barrier property of adult maize leaf cuticles.

Resonant-antiresonant coupled cavity VCSELs.

The wavelength tuning range of a tunable vertical-cavity surface-emitting laser (VCSEL) is strongly influenced by the design of the interface between the semiconductor cavity and the air cavity. A simplified model is used to investigate the origin of the dramatic differences in free spectral range (FSR) and tuning slope observed in semiconductor cavity dominant, extended cavity, and air cavity dominant VCSELs. The differences arise from the positioning of the resonant and antiresonant wavelengths of the semiconductor cavity with respect to the center wavelength. The air cavity dominant design is realized by designing an antiresonant semiconductor cavity, resulting in a larger tuning slope near the center of the tuning range and a wider FSR toward the edges of the tuning range. The findings from the simplified model are confirmed with the simulation of a full VCSEL structure. Using an air cavity dominant design, an electrically pumped laser with a tuning range of 68.38 nm centered at 1056.7 nm at a 550 kHz sweep rate is demonstrated with continuous wave emission at room temperature. This epitaxial design rule can be used to increase the tuning range of tunable VCSELs, making them more applicable in swept-source optical coherence tomography and frequency-modulated continuous-wave LIDAR systems.

Evaluation and application of donors with primary central nervous system tumors.

BACKGROUND: This study aimed to explore the safety of donors with primary central nervous system tumors for kidney and liver transplantations. METHODOLOGY: Clinical data of 29 donors with primary CNS tumors in January 2007 to December 2017, as well as the follow-up data of 16 liver transplant recipients and 46 kidney transplant recipients, were analyzed. According to the risk factors, the high-risk group was classified as Group 1, the low-risk factors were classified as Group 2, and the unknown risk group was classified as Group 3. The incidence of donor-transmitted CNS tumors was calculated and compared. RESULTS: The duration from the diagnosis of 29 donors to donation was 5.67 ± 6.36 months. None of the liver and kidney transplant recipients who were followed up had tumor metastasis. Although the mean survival time of Group 1 was lower than that of Group 2 and Group 3, the Kaplan-Meier curve showed no significant difference in survival time. CONCLUSION: No obvious difference was observed between high-risk and low-risk and unknown risk CNS tumors in terms of the survival rate of transplants and tumor metastasis rate. High-risk CNS tumor donors can be used with the informed consent of recipients after a full evaluation.

Differential study of DCE-MRI parameters in spinal metastatic tumors, brucellar spondylitis and spinal tuberculosis.

OBJECTIVE: In the present study, spinal metastatic tumors, brucellar spondylitis and spinal tuberculosis were quantitatively analyzed using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to assess the value of DCE-MRI in the differential diagnosis of these diseases. METHODS: Patients with brucellar spondylitis, spinal tuberculosis or a spinal metastatic tumor (30 cases of each) received conventional MRI and DCE-MRI examination. The volume transfer constant (Ktrans), rate constant (Kep), extravascular extracellular volume fraction (Ve) and plasma volume fraction (Vp) of the diseased vertebral bodies were measured on the perfusion parameter map, and the differences in these parameters between the patients were compared. RESULTS: For pathological vertebrae in cases of spinal metastatic tumor, brucellar spondylitis and spinal tuberculosis, respectively, the Ktrans values (median ± quartile pitch) were 0.989±0.014, 0.720±0.011 and 0.317±0.005 min-1; the Kep values were 2.898±0.055, 1.327±0.017 and 0.748±0.006 min-1; the Ve values were 0.339±0.008, 0.542±0.013 and 0.428±0.018; the Vp values were 0.048±0.008, 0.035±0.004 and 0.028±0.009; the corresponding H values were 50.25 (for Ktrans), 52.47 (for Kep), 48.33 (for Ve) and 46.56 (for Vp), and all differences were statistically significant (two-sided P<0.05). CONCLUSIONS: The quantitative analysis of DCE-MRI has a certain value in the differential diagnosis of spinal metastatic tumor, brucellar spondylitis and spinal tuberculosis.

Widely tunable 1060-nm VCSEL with high-contrast grating mirror.

We report tunable VCSELs emitting around 1060 nm, enabled by high-contrast grating (HCG) mirror. Single-mode continuous-wave (CW) operation up to 110 °C is demonstrated, with room-temperature single-mode output power >1.3 mW at a very low threshold of ~300 µA. The obtained thermal resistance of 0.88 °C/mW is low for VCSELs with an oxide-confined laser aperture. A wide, continuous tuning range up to 40 nm was achieved with electrostatic and thermal tuning, at a fast tuning speed up to 1.15 MHz. In addition, we developed transverse-mode control designs of HCGs to greatly improve the single-mode yield of oxidized VCSELs. The cost-effective, wafer-scale fabrication makes these VCSELs promising as tunable light sources for swept-source optical coherent tomography (SS-OCT) and LiDAR applications.

MEMS-tunable VCSELs using 2D high-contrast gratings.

We demonstrate the room-temperature operation of a two-dimensional (2D) high-contrast grating (HCG) vertical-cavity surface-emitting laser (VCSEL) at 1080 nm. To the best of our knowledge, this is the first tunable electrically pumped surface-emitting laser using a 2D HCG. Our theory successfully explains the mechanism of broadband ultrahigh reflection of 2D HCGs. Our monolithic integrated laser exhibits single-mode output power above 0.68 mW under continuous-wave operation. Wavelength tunability is demonstrated via microelectromechanical system-controlled voltage.

Resting-State fMRI findings in patients with first-Episode idiopathic epilepsy before and after treatment.

OBJECTIVE: To detect resting-state functional MRI (rsfMRI) changes and their relationships with the clinical curative effect of anti-epileptic drugs (AEDs) for complex partial seizures (CPS) in epilepsy patients using the fractional amplitude of low frequency fluctuation (fALFF). METHODS: rfMRI data from 14 CPS patients enrolled between June 2015 and June 2016 in Department of Neurology, Affiliated Hospital of Inner Mongolia Medical University were retrospectively investigated and compared with findings from 14 healthy age-, gender-, handedness-, and education-matched subjects. The patients were treated with first-line antiepileptic drugs for 12 weeks before undergoing a second rfMRI scan. fALFF data were processed using REST and SPM8 software. Whole-brain data were compared between the 2 groups. RESULTS: The abnormal findings in CPS patients significantly decreased or disappeared after AED treatment. CONCLUSION: Measuring fALFF is useful for identifying brain functional changes in patients with first-episode epilepsy before and after treatment. Performing rfMRI is useful for evaluating treatment responses and may provide new insight into the pathophysiological mechanisms of epilepsy.

Theory and design of two-dimensional high-contrast-grating phased arrays.

Optical properties of two-dimensional (2D) high-contrast gratings are investigated. We analyze the mechanisms for high-contrast gratings to function as various high-performance optical components. Our top-down design procedure allows us to efficiently obtain initial structural parameters and engineer them for a wide range of applications, such as reflectors, filters, resonators, waveplates, and even 2D phase plates. Simulation results of our designed structures show ultra-high power efficiency, and excellent agreement with our predicted functionalities.

Heterogeneously integrated long-wavelength VCSEL using silicon high contrast grating on an SOI substrate.

We report an electrically pumped hybrid cavity AlGaInAs-silicon long-wavelength VCSEL using a high contrast grating (HCG) reflector on a silicon-on-insulator (SOI) substrate. The VCSEL operates at silicon transparent wavelengths ~1.57 µm with >1 mW CW power outcoupled from the semiconductor DBR, and single-mode operation up to 65 °C. The thermal resistance of our device is measured to be 1.46 K/mW. We demonstrate >2.5 GHz 3-dB direct modulation bandwidth, and show error-free transmission over 2.5 km single mode fiber under 5 Gb/s direct modulation. We show a theoretical design of SOI-HCG serving both as a VCSEL reflector as well as waveguide coupler for an in-plane SOI waveguide, facilitating integration of VCSEL with in-plane silicon photonic circuits. The novel HCG-VCSEL design, which employs scalable flip-chip eutectic bonding, may enable low cost light sources for integrated optical links.

microRNA-34a inhibits epithelial mesenchymal transition in human cholangiocarcinoma by targeting Smad4 through transforming growth factor-beta/Smad pathway.

BACKGROUND: Extrahepatic Cholangiocarcinoma (EHCC) is one of the uncommon malignancies in the digestive system which is characterized by a poor prognosis. Aberrations of miRNAs have been shown involved in the progression of this disease. In this study, we evaluated the expression and effects of miR-34a on EHCC. METHODS: miR-34a expression levels were detected in EHCC tissues, adjacent non-tumor tissues, normal bile duct (NBD) specimens of patients and cholangiocarcinoma (CC) cell lines by quantitative real-time polymerase chain reaction (qRT-PCR). Relationships between miR-34a with clinical characteristics of EHCC patients were further analyzed. Computational search, functional luciferase assay and western blot were further used to demonstrate the downstream target of miR-34a in CC cells. Immunohistochemistry was carried on to identify the downstream target gene of miR-34a in EHCC patients. Cell morphology, invasion and migration assays were further applied to confirm the anti-carcinogenic effects of miR-34a through the downstream target. RESULTS: miR-34a expression was significantly decreased in human EHCC tissues and CC cell lines when compared with the adjacent non-tumor tissues and normal bile duct tissues. miR-34a was found correlated with the migration and invasion in EHCC patients. Smad4 was over-expressed in most of the EHCC patients and was further demonstrated as one of the downstream targets of miR-34a, which was involved in the progression of EHCC. Moreover, activation of miR-34a suppressed invasion and migration through TGF-beta/Smad4 signaling pathway by epithelial-mesenchymal transition (EMT) in vitro. CONCLUSIONS: Taken together, our results suggest that miR-34a inhibits invasion and migration by targeting Smad4 to suppress EMT through TGF- beta/Smad signaling pathway in human EHCC.

Comprehensive model of 1550 nm MEMS-tunable high-contrast-grating VCSELs.

A comprehensive theoretical model for the long-wavelength micro-electro-mechanical-tunable high-contrast-grating vertical-cavity surface-emitting lasers is presented. Our band structure model calculates the optical gain and spontaneous emission of the InGaAlAs quantum well active region. The grating reflectivity and the cavity resonance condition are investigated through optical modeling. Correlating the results with the electrostatic model for the micro-electro-mechanical system, we accurately predict the measurements on the voltage-contolled lasing wavelength. Furthermore, our calculated temperature-dependent wavelength-tunable light output vs. current (L-I) curves show excellent agreement with experiment.

Clinical characteristics, treatment patterns and survival outcome of hepatocellular carcinoma patients aged 70 years or older: a single-center retrospective study from China.

BACKGROUND AND AIMS: The information about clinical presentation and outcome of elderly hepatocellular carcinoma (HCC) patients is limited. We performed this study to assess the impact of age on potential differences in clinical characteristics, treatment patterns and outcome in HCC patients. METHODS: Clinical data of 164 "elderly" (≥70 years old) and 531 "younger" (<70 years old) HCC patients treated at a Chinese tertiary university-affiliated medical center between April 2004 and April 2012 were collected and compared using various parameters. RESULTS: Compared with younger patients, the elderly patients had a higher proportion of females (32.9 % vs. 18.1 %, p < 0.001), less hepatitis B virus (HBV) infection (40.9 % vs. 76.6 %, p < 0.001), more hepatitis C virus (HCV) infection (23.8 % vs. 5.6 %, p < 0.001), less liver cirrhosis (68.3 % vs. 76.8 %, p = 0.03) and massive tumors (12.8 % vs. 21.8 %, p = 0.01). There was no significant difference between the two groups in Child-Pugh class and tumor stages. The elderly patients received less surgical resection (14.6 % vs. 29.6 %, p < 0.001) and more supportive care (48.8 % vs. 37.9 %, p = 0.01) than younger patients. The overall survival was not significantly different between the two groups (26.2 mo. vs. 28.3 mo., p = 0.75). CONCLUSION: Characteristics that distinguish elderly from younger HCC patients included more female, less HBV infection, more HCV infection, less liver cirrhosis and massive tumors. Significant differences were observed in therapeutic strategies utilized with the two groups, but the overall survival was not significantly different.

Theory and experiment of submonolayer quantum-dot metal-cavity surface-emitting microlasers.

We present a theoretical model for metal-cavity submonolayer quantum-dot surface-emitting microlasers, which operate at room temperature under electrical injection. Size-dependent lasing characteristics are investigated experimentally and theoretically with device radius ranging from 5 µm to 0.5 µm. The quantum dot emission and cavity optical properties are used in a rate-equation model to study the laser light output power vs. current behavior. Our theory explains the observed size-dependent physics and provides a guide for future device size reduction.

The causal effect of serum micronutrients on malignant kidney neoplasm in European descent.

Purpose: Observational studies have revealed that serum minerals and vitamins are associated with cancer. However, the causal relationships between serum minerals and vitamins and renal malignancies remain unclear. Methods: Mendelian randomization (MR) was used for causal estimation. Single nucleotide polymorphisms (SNPs) for serum minerals and vitamins were obtained from published genome-wide association studies (GWAS). GWAS for malignant kidney neoplasm was obtained from the FinnGen consortium. Methods of inverse variance weighted (IVW), MR-Egger, and weighted median were carried out for causal inference. F-statistic was calculated to ensure a robust instrumental variable. Cochran's Q statistics was applied to calculate heterogeneity. MR-Egger regression, MR-pleiotropy residual sum and outlier methods (MR-PRESSO) methods were used to perform pleiotropy analysis. Meanwhile, confounding factors were considered to determine whether causal inference would be biased. Results: Eight different micronutrients were included (zinc, iron, magnesium, calcium, copper, selenium, phosphate, and vitamin B12). After MR analysis, we found a protective effect of serum zinc against malignant kidney neoplasm (IVW: odds ratios (ORs), 0.86; 95% confidence interval (95% CI), 0.78-0.94; p, 0.0016; MR-Egger: OR, 0.80; 95% CI, 0.64-0.97; p, 0.052; weighted median: OR, 0.85; 95% CI, 0.75-0.96; p, 0.011). Causal relationships between other micronutrients and malignant kidney neoplasm were not obtained. No heterogeneity and pleiotropy were detected, while causality was not biased by confounding factors. Conclusion: We considered that serum zinc exerted a protective effect against malignant kidney neoplasm. In clinical practice, for people with high malignant kidney neoplasm risk, an oral zinc supplementation might play a role in a potential therapeutic target.

Application of tumoroids derived from advanced colorectal cancer patients to predict individual response to chemotherapy.

Therapeutic approaches of advanced colorectal cancer are more complex, here we present a living biobank of patient-derived tumoroids from advanced colorectal cancer patients and show examples of how these tumoroids can be used to to simulate cancer behavior ex vivo and provide more evidence for tumoroids could be utilized as a predictive platform during chemotherapy treatment to identify the chemotherapy response. Morphological, histological and genomic characterization analysis of colorectal cancer tumoroids was conducted. Further, we treated colorectal cancer tumoroids with different drugs to detect cellular activities to evaluate drug sensitivity using CellTiter-Glo 3 D cell viability assay. Then the drug sensitivity of tumoroids was compared with clinical outcomes. Our results implied that tumoroids recapitulated the histological features of the original tumours and genotypic profiling of tumoroids showed a high-level of similarity to the matched primary tumours. Dose-response curves, area under the curve and tumour inhibitory rate of each therapeutic profiling calculations in tumoroids demonstrated a great diversity and we gained 88.24% match ratio between the sensitivity data of tumoroids with their paired patients' clinical outcomes. tumour inhibitory rate of each treatment parameters in tumoroids performed positive correlation with progression-free survival while area under the curve of each treatment parameters performed negative correlation with progression-free survival of the corresponding patients. In summary, We presented a living biobank of tumoroids from advanced colorectal cancer patients and show tumoroids got great potential for predicting clinical responses to chemotherapy treatment of advanced colorectal cancer.

Genomic Island-Encoded Histidine Kinase and Response Regulator Coordinate Mannose Utilization with Virulence in Enterohemorrhagic Escherichia coli.

Enterohemorrhagic Escherichia coli (EHEC) is a highly adaptive pathogen and has acquired diverse genetic elements, such as genomic islands and prophages, via horizontal gene transfer to promote fitness in vivo. Two-component signaling systems (TCSs) allow bacteria to sense, respond to, and adapt to various environments. This study identified a putative two-component signaling system composed of the histidine kinase EDL5436 (renamed LmvK) and the response regulator EDL5428 (renamed LmvR) in EHEC. lmvK and lmvR along with EDL5429 to EDL5434 (EDL5429-5434) between them constitute the OI167 genomic island and are highly associated with the EHEC pathotype. EDL5429-5434 encode transporters and metabolic enzymes that contribute to growth on mannose and are directly upregulated by LmvK/LmvR in the presence of mannose, as revealed by quantitative PCR (qPCR) and DNase I footprint assays. Moreover, LmvR directly activates the expression of the type III secretion system in response to mannose and promotes the formation of attaching and effacing lesions on HeLa cells. Using human colonoid and mouse infection models, we show that lmvK and lmvR contributed greatly to adherence and microcolony (MC) formation ex vivo and colonization in vivo. Finally, RNA sequencing and chromatin immunoprecipitation coupled with sequencing analyses identified additional direct targets of LmvR, most of which are involved in metabolism. Given that mannose is a mucus-derived sugar that induces virulence and is preferentially used by EHEC during infection, our data revealed a previously unknown mechanism by which EHEC recognizes the host metabolic landscape and regulates virulence expression accordingly. Our findings provide insights into how pathogenic bacteria evolve by acquiring genetic elements horizontally to adapt to host environments. IMPORTANCE The gastrointestinal tract represents a complex and challenging environment for enterohemorrhagic Escherichia coli (EHEC). However, EHEC is a highly adaptable pathogen, requiring only 10 to 100 CFUs to cause infection. This ability was achieved partially by acquiring mobile genetic elements, such as genomic islands, that promote overall fitness. Mannose is an intestinal mucus-derived sugar that stimulates virulence and is preferentially used by EHEC during infection. Here, we characterize the OI167 genomic island of EHEC, which encodes a novel two-component signaling system (TCS) and transporters and metabolic enzymes (EDL5429-5434) involved in mannose utilization. The TCS directly upregulates EDL5429-5434 and genes encoding the type III secretion system in the presence of mannose. Moreover, the TCS contributes greatly to EHEC virulence ex vivo and in vivo. Our data demonstrate an elegant example in which EHEC strains evolve by acquiring genetic elements horizontally to recognize the host metabolic landscape and regulate virulence expression accordingly, leading to successful infections.