Characterization of Serotypes and Molecular Drug Resistance Patterns of Haemophilus influenzae in Kunming Children.

The present study aimed to determine the capsular serotype distribution and antimicrobial drug resistance patterns of Haemophilus influenzae from children in the Kunming region of China. This information could guide policymakers in clinical treatment. In the present study, H. influenzae isolates were tested for their serotypes, antimicrobial susceptibility pattern, and presence of ß-lactamases. One-hundred forty-eight H. influenzae strains isolated from children 0-2 years old were investigated for capsular types by glass slide agglutination and molecular methods, and biotyped by the biochemical reactions. The drug resistance-encoding genes TEM-1, ROB-1, and the ftsI gene mutations PBP3-3, and PBP3-BLN were detected with real-time quantitative polymerase chain reaction (qPCR). The prevalence of ß-lactamase-producing strains (60.3%) was significantly higher (p < 0.05) than non-enzyme-producing strains. ß-Lactamase-producing strains were multidrug resistant to various antibiotics such as ampicillin, tetracycline, sulfamethoxazole/trimethoprim, chloramphenicol, cefuroxime, and cefaclor. Among ß-lactamase-producing strains, the detection rates of the TEM-1, PBP3-BLN, PBP3-s, and ROB-1 were 54.1%, 18.9%, 11.8%, and 6.9%, respectively. The biotyping results show that most H. influenzae strains were of type II and III. Non-typeable H. influenzae (NTHi) accounted for 89.3% of the strains. NTHi strains were the most prevalent in this region; most belonged to biological types II and III. ß-Lactamase-positive ampi-cillin-resistant (BLPAR) strains were prevalent among H. influenzae isolates in this region.

Semiannual Breast US or MRI Screening in Patients with a Personal History of Breast Cancer.

Background The wide variability of screening imaging use in patients with a personal history of breast cancer (PHBC) warrants investigation of its comparative clinical effectiveness. While more intensive screening with US or MRI at an interval of less than 1 year could increase early-stage breast cancer detection, its benefit has not been established. Purpose To investigate the outcomes of semiannual multimodality screening in patients with PHBC. Materials and Methods An academic medical center database was retrospectively searched for patients diagnosed with breast cancer between January 2015 and June 2018 who had undergone annual mammography with either semiannual incidence US or MRI screening from July 2019 to December 2019 and three subsequent semiannual screenings over a 2-year period. The primary outcome was second breast cancers diagnosed during follow-up. Examination-level cancer detection and interval cancer rates were calculated. Screening performances were compared with χ2 or Fisher exact tests or a logistic model with generalized estimating equations. Results Our final cohort included 2758 asymptomatic women (median age, 53 years; range, 20-84 years). Among 5615 US and 1807 MRI examinations, 18 breast cancers were detected after negative findings on a prior semiannual incidence US screening examination; 44% (eight of 18) were stage 0 (three detected with MRI; five, with US), and 39% (seven of 18) were stage I (three detected with MRI; four, with US). MRI had a cancer detection rate up to 17.1 per 1000 examinations (eight of 467; 95% CI: 8.7, 33.4), and the overall cancer detection rates of US and MRI were 1.8 (10 of 5615; 95% CI: 1.0, 3.3) and 4.4 (eight of 1807; 95% CI: 2.2, 8.8) per 1000 examinations, respectively (P = .11). Conclusion Supplemental semiannual US or MRI screening depicted second breast cancers after negative findings at prior semiannual incidence US examination in patients with PHBC. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Berg in this issue.

Design, synthesis, and biological evaluation of acyl sulfonamide derivatives with spiro cycles as NaV1.7 inhibitors for antinociception.

Chronic pain, as an unmet medical need, severely impacts the quality of life. The voltage-gated sodium channel NaV1.7 preferentially expressed in sensory neurons of dorsal root ganglia (DRG) serves a promising target for pain therapy. Here, we report the design, synthesis, and evaluation of a series of acyl sulfonamide derivatives targeting Nav1.7 for their antinociceptive activities. Among the derivatives tested, the compound 36c was identified as a selective and potent NaV1.7 inhibitor in vitro and exhibited antinociceptive effects in vivo. The identification of 36c not only provides a new insight into the discovery of selective NaV1.7 inhibitors, but also may hold premise for pain therapy.

Identification and Prognostic Effect of Extramural Venous Invasion in Locally Advanced Esophageal Squamous Cell Carcinoma.

The role of extramural venous invasion (EMVI) in esophageal cancer is still unclear. This study aimed to identify EMVI and assess its impact on survival and recurrences in esophageal squamous cell carcinoma (ESCC). Retrospectively, we reviewed resection specimens of 147 locally advanced ESCC (pT3-T4aN0-3M0) patients who had a curative intended surgery alone at the Cancer Hospital of Shantou University from March 2009 to December 2013. After confirming pT≥3 in hematoxylin-eosin tumor slides, EMVI was evaluated by Verhoeff and Caldesmon staining. The impact of EMVI with other clinicopathological characteristics and survival were analyzed using the χ2 test, Cox regression, and Kaplan-Meier method. EMVI was present in 30.6% (45/147) of the P≥T3 ESCCs and associated with lymph-vascular invasion and poor differentiation grade (P<0.05). Disease-free survival and overall survival in patients with EMVI-absent tumors were about 2.0 times longer than in those with EMVI-present tumors. In pN0 patients, EMVI-presence was associated with poor overall survival (HR 4.829, 95% CI 1.434-16.26, P=0.003) and Disease-free Survival (HR 4.026, 95% CI 0.685-23.32, P=0.018). In pN1-3 patients, EMVI had no additional effect on survival. Conclusions EMVI has an independent adverse prognostic effect on survival in ESCC patients after surgery alone. EMVI should be included in pathology reports as it might contribute to identify high-risk patients for potential additional treatment.

Tat-RAN attenuates brain ischemic injury in hippocampal HT-22 cells and ischemia animal model.

Oxidative stress plays a key role in the pathogenesis of neuronal injury, including ischemia. Ras-related nuclear protein (RAN), a member of the Ras superfamily, involves in a variety of biological roles, such as cell division, proliferation, and signal transduction. Although RAN reveals antioxidant effect, its precise neuroprotective mechanisms are still unclear. Therefore, we investigated the effects of RAN on HT-22 cell which were exposed to H2O2-induced oxidative stress and ischemia animal model by using the cell permeable Tat-RAN fusion protein. We showed that Tat-RAN transduced into HT-22 cells, and markedly inhibited cell death, DNA fragmentation, and reactive oxygen species (ROS) generation under oxidative stress. This fusion protein also controlled cellular signaling pathways, including mitogen-activated protein kinases (MAPKs), NF-κB, and apoptosis (Caspase-3, p53, Bax and Bcl-2). In the cerebral forebrain ischemia animal model, Tat-RAN significantly inhibited both neuronal cell death, and astrocyte and microglia activation. These results indicate that RAN significantly protects against hippocampal neuronal cell death, suggesting Tat-RAN will help to develop the therapies for neuronal brain diseases including ischemic injury.

Effects of Dongchimi Powder as a Natural Nitrite Source on Quality Properties of Emulsion-Type Sausages.

The use of nitrite as a conventional curing agent is decreasing because of the negative consumer perception of synthetic compounds in foods. Therefore, this study was conducted to investigate the efficacy of dongchimi as an alternative to synthetic nitrite and its effect on the qualitative properties of emulsion-type sausages. Under all tested fermentation conditions, both nitrite and nitrate contents were the highest when dongchimi was fermented at 0°C for 1 wk. The fermented dongchimi was powdered and added to the sausages. Emulsion-type sausages were prepared with 0.25% (treatment 1), 0.35% (treatment 2), 0.45% (treatment 3), or 0.55% (treatment 4) dongchimi powder, with 0.01% sodium nitrite-treated (control 1) and 0.40% celery powder-treated (control 2) sausages as controls. There were not different (p>0.05) in the pH, cooking yield, CIE L*, and CIE a* between the control 1 and treatments 2, 3, and 4. CIE b* was significantly higher (p<0.05) in the control 2 and lower (p<0.05) in the control 1 than that in the other groups. Treatment 4 and control 1 had similar contents of residual nitrite, nitrosyl hemochrome, and total pigment. Additionally, treatment 4 exhibited a significantly better (p<0.05) curing efficiency than the control 1. However, naturally cured sausages showed higher (p<0.05) lipid oxidation than the control 1. This study suggests that the use of more than 0.35% dongchimi powder could replace sodium nitrite or celery powder as curing agents for emulsion-type sausages.

Role of Multimodality Imaging in Transcatheter Structural Interventions.

Cardiac imaging is the backbone for safe and optimal transcatheter structural interventions. Transthoracic echocardiogram is the initial modality to assess valvular disorders, while transesophageal echocardiogram is best to delineate the mechanism of valvular regurgitation, preprocedural assessment for transcatheter edge-to-edge repair, and for intraprocedural guidance. Cardiac computed tomography is the modality of choice for assessing calcifications, maneuvering multiplaner reconstruction of different cardiac structures, preprocedural planning for various transcatheter valve replacement, and assessing for hypoattenuated leaflet thickening and reduced leaflet motion. Cardiac magnetic resonance imaging is best known for most accurate volumetric assessment of valvular regurgitation and chamber size quantification. Cardiac positron emission tomography is the only modality that could assess active infection through using fluorine 18 fluorodeoxyglucose radiotracer.

Kaempferitrin, a major compound from ethanol extract of Chenopodium ambrosioides, exerts antitumour and hepatoprotective effects in the mice model of human liver cancer xenografts.

OBJECTIVES: This study aimed to investigate antitumour effect and possible toxicity of kaempferitrin, the major compound from ethanol extract of Chenopodium ambrosioides, in the mice model of human liver cancer xenografts. METHODS: Forty mice bearing SMMC-7721 cells xenografts were divided into control group (not treated) and three groups orally administered with ethanol extract of C. ambrosioides, kaempferol (positive control) and kaempferitrin for 30 days. Antitumour effect was evaluated by measurement of tumour growth, histological examinations of tumours, flow cytometry detection of splenic CD19+ B lymphocytes and CD161+ Natural Killer cells, biochemical measurements of serum levels of tumour necrosis factor-α, interleukin-6, interferon-γ, malonaldehyde, 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azinobis-(3-ethylbenz thiazoline-6-sulphonate) radicals. Toxicity was evaluated by histological examinations of livers and measurements of serum levels of aspartate transaminase, alanine transaminase, total bilirubin, direct bilirubin, malonaldehyde and hepatic malonaldehyde level. KEY FINDINGS: Kaempferitrin significantly (P < 0.05) decreased tumour volume, mass and cell number. Antitumour effect was due to induction of tumour cells necrosis and apoptosis, stimulation of splenic B lymphocytes, decreases of radicals and malonaldehyde. Kaempferitrin did not change liver structure, and decreased serum levels of transaminases, bilirubin, malonaldehyde and hepatic malonaldehyde level. CONCLUSIONS: Kaempferitrin exerts antitumour and hepatoprotective effects.

Intrahepatic cholelithiasis with gallbladder-like metaplasia of intrahepatic bile ducts associated with gallbladder agenesis in a wild boar.

An unknown-aged adult female wild boar (Sus scrofa) was brought to Kyungpook National University for postmortem examination. Gross examination revealed gallbladder agenesis. Histologically, the liver was cirrhotic and had intrahepatic cholelithiasis, the choleliths were yellow, brown, gray, and black, and had coffin-lid and pyramidal appearances. Fourier-transform infrared spectroscopy analysis revealed that the components were 80% struvite and 20% calcium oxalate monohydrate. Chronic inflammatory cell infiltration was observed, with hyperplastic hepatocellular nodules characterized by large nuclei, prominent nucleoli, and scant cytoplasm with frequent binucleation, surrounded by thick fibrous septa. The epithelium of intrahepatic bile ducts that contained choleliths had undergone gallbladder-like metaplasia, which might have been induced by chronic irritation from the stones or by the accompanying chronic bacterial infection that was observed in Gram stains.

Gene expression of Toll-like receptors, cytokines and a nuclear factor and cytokine secretion in DH82 canine macrophage cells infected with Brucella canis.

Canine brucellosis caused by Brucella canis infection occurs mainly in dogs, and is a zoonotic disease that also has the possibility of infection in humans. Many studies have been conducted to understand the immunopathological mechanism of B. canis infection. However, the precise immune mechanism remains to be elucidated because compared to other Brucella spp., B. canis has different immune evasion mechanisms. In this study, gene expression levels of Toll-like receptors (TLRs) and TLR-associated molecules and cytokine production were analyzed to figure out the roles of immune-related host factors in B. canis infection. Time-dependent gene expression of TLRs (1-10) and TLR-related molecules (TNF-α, IL-5, IL-23, CCL4, CD40 and NFκ-B) and release of Th1, Th2 and Th17-related cytokines (IFN-γ, IL-1ß, IL-4, IL-6, IL-10 and IL-17A) were investigated in DH82 canine macrophages infected with B. canis. Time-dependent induction of TLRs 3, 7 and 8 was observed, and TLR 7 had the highest expression level (p <0.05). The expression levels of all TLR-related genes were significantly increased after infection. In particular, the expression of the CCL4 and IL-23 genes was highly induced. The amounts of IL-1ß, IL-6 and IL-10 were significantly increased by B. canis infection, but the amounts of IL-4 and IL-17A were not. The production of IL-1ß and IL-6 was the highest at 24 hr after B. canis infection (p <0.05). This study demonstrates that TLRs 3, 7 and 8 are prominent sites of to immune response induction with the production of related cytokines and a nuclear factor in DH82 cells infected with B. canis. These results suggest a sequential immune mechanism of B. canis infection, involving TLRs, cytokines and their associated factors.

Using Real-Time Interaction Analysis to Explore Human-Robot Interaction.

Despite the increasing presence of social robots (SRs) in Human-Robot Interaction, there are few studies that quantify these interactions and explore children's attitudes by analyzing real-time data as they communicate with SRs. Therefore, we attempted to explore the interaction between pediatric patients and SRs by analyzing the interaction log collected from real-time. This study is a retrospective analysis of data collected in a prospective study conducted on 10 pediatric cancer patients at tertiary hospitals in Korea. Using the Wizard of Oz method, we collected the interaction log during the interaction between pediatric cancer patients and the robot. Out of the collected data, 955 sentences from the robot and 332 sentences from the children were available for analysis, except for the logs that were missing due to environmental errors. we analyzed the delay time from saving the interaction log and the sentence similarity of the interaction log. The interaction log delay time between robot and child was 5.01 seconds. And the child's delay time averaged 7.2 seconds, which was longer than the robot's delay time of 4.29 seconds. Additionally, as a result of analyzing the sentence similarity of the interaction log, the robot (97.2%) was higher than the children (46.2%). The results of the sentiment analysis of the patient's attitude toward the robot were 73% neutral, 13.59% positive, and 12.42% negative. The observational evaluations of pediatric psychological experts identified curiosity (n=7, 70.0%), activity (n=5, 50.0%), passivity (n=5, 50.0%), sympathy (n=7, 70.0%), concentration (n=6, 60.0%), high interest (n=5, 50.0%), positive attitude (n=9, 90.0%), and low interaction initiative (n=6, 60.0%). This study made it possible to explore the feasibility of interaction with SRs and to confirm differences in attitudes toward robots according to child characteristics. To increase the feasibility of human-robot interaction, measures such as improving the completeness of log records by enhancing the network environment are required.

E. urophylla × E. grandis high-quality genome and comparative genomics provide insights on evolution and diversification of eucalyptus.

BACKGROUND: Eucalyptus urophylla × Eucalyptus grandis, an economically important forest tree, provides important raw material for energy and reduces damage to native forests. However, the absence of a high-quality E. urophylla × E. grandis reference genome has significantly hindered its evolution and genetic analysis. RESULTS: We successfully presented a high-quality reference genome of E. urophylla × E. grandis (545.75 Mb; scaffold N50, 51.62 Mb) using a combination of the Illumina, PacBio HiFi, and Hi-C sequencing platforms. A total of 34,502 genes and 58.56% of the repetitive sequences in this genome were annotated. Using genome evolution analyses, we identified a recent whole-genome duplication (WGD) event in E. urophylla × E. grandis. We further found that gene families associated with starch and sucrose metabolism, flavonoid biosynthesis, and plant-pathogen interaction were significantly expanded in E. urophylla × E. grandis. Moreover, comparative genomic and evolutionary analyses showed large structural variations among the different chromosomes of the 34 Eucalyptus accessions, which were divided into six clades. CONCLUSIONS: Overall, our findings provide a valuable resource for expanding our understanding of the E. urophylla × E. grandis genome evolution, genetic improvement, and its comparative biology.

Study on the standard components of digital forensics laboratory.

Recently, digital forensics has become increasingly important as it is used by investigation agencies, corporate, and private sector. To supplement the limitations of evidence capacity and be recognized in court, it is essential to establish an environment that ensures the integrity of the entire process ranging from collecting and analyzing to submitting digital evidence to court. In this study, common elements were extracted by comparing and analyzing ISO/IEC 17025, 27001 standards and Interpol and Council of Europe (CoE) guidelines to derive the necessary components for building a digital forensic laboratory. Subsequently, based on 21 digital forensic experts in the field, Delphi survey and verifications were conducted in three rounds. As a result, 40 components from seven areas were derived. The research results are based on the establishment, operation, management, and authentication of a digital forensics laboratory suitable for the domestic environment, with added credibility through collection of the opinions of 21 experts in the field of digital forensics in Korea. This study can be referred to in establishing digital forensic laboratories in national, public, and private digital forensic organizations as well as for employing as competency measurement criteria in courts to evaluate the reliability of the analysis results.

High-Resolution Tactile-Sensation Diagnostic Imaging System for Thyroid Cancer.

In this study, we propose the direct diagnosis of thyroid cancer using a small probe. The probe can easily check the abnormalities of existing thyroid tissue without relying on experts, which reduces the cost of examining thyroid tissue and enables the initial self-examination of thyroid cancer with high accuracy. A multi-layer silicon-structured probe module is used to photograph light scattered by elastic changes in thyroid tissue under pressure to obtain a tactile image of the thyroid gland. In the thyroid tissue under pressure, light scatters to the outside depending on the presence of malignant and positive properties. A simple and easy-to-use tactile-sensation imaging system is developed by documenting the characteristics of the organization of tissues by using non-invasive technology for analyzing tactile images and judging the properties of abnormal tissues.

[Interpretation of Image-Guided Biopsy Results and Assessment]. / ì˜ìƒìœ ë„í•˜ 조직검사의 해석과 íŒì •.

The success of image-guided breast biopsy depends on the biopsy method, needle selection, and appropriate technique based on the accurate judgment by the radiologist at biopsy. However, insufficient or inappropriate sampling of specimens may result in false-negative results or pathologic underestimation. Therefore, image-pathology concordance assessments after biopsy are essential for appropriate patient management. Particularly, the assessment of image-pathology concordance can avoid false-negative reports of breast cancer as a benign pathology. Therefore, this study aimed to discuss factors that impact the accurate interpretation of image-guided breast biopsy along with the appropriate assessments.

Genetic investigation of 124 SNPs in a Myanmar population using the Precision ID Identity Panel and the Illumina MiSeq.

Single nucleotide polymorphisms (SNPs) have become popular in forensic genetics as an alternative to short tandem repeats (STRs). The Precision ID Identity Panel (Thermo Fisher Scientific), consisting of 90 autosomal SNPs and 34 Y-chromosomal SNPs, enabled human identification studies on global populations through next-generation sequencing (NGS). However, most previous studies on the panel have used the Ion Torrent platform, and there are few reports on the Southeast Asian population. Here, a total of 96 unrelated males from Myanmar (Yangon) were analyzed with the Precision ID Identity Panel on a MiSeq (Illumina) using an in-house TruSeq compatible universal adapter and a custom variant caller, Visual SNP. The sequencing performance evaluated by locus balance and heterozygote balance was comparable to that of the Ion Torrent platform. For 90 autosomal SNPs, the combined match probability (CMP) was 6.994 × 10-34, lower than that of 22 PowerPlex Fusion autosomal STRs (3.130 × 10-26). For 34 Y-SNPs, 14 Y-haplogroups (mostly O2 and O1b) were observed. We found 51 cryptic variations (42 haplotypes) around target SNPs, of which haplotypes corresponding to 33 autosomal SNPs decreased CMP. Interpopulation analysis revealed that the Myanmar population is genetically closer to the East and Southeast Asian populations. In conclusion, the Precision ID Identity Panel can be successfully analyzed on the Illumina MiSeq and provides high discrimination power for human identification in the Myanmar population. This study broadened the accessibility of the NGS-based SNP panel by expanding the available NGS platforms and adopting a robust NGS data analysis tool.

High FN1 expression is associated with poor survival in esophageal squamous cell carcinoma.

Esophageal cancer (EC) is a serious threat to human health. The expression of fibronectin 1 (FN1) in esophageal squamous cell carcinoma (ESCC) remains controversial. The purpose of this study was to elucidate the expression of FN1 in ESCC and to assess the value of FN1 in the prognosis of ESCC patients. 100 ESCC patients from January 2015 to March 2016 were recruited in this study. qRT-PCR and immunohistochemistry (IHC) were used to detect FN1 mRNA and protein expression. The correlation between FN1 expression levels and prognosis of ESCC patients was analyzed. The qRT-PCR results showed that the expression of FN1 mRNA was significantly higher in ESCC tumor tissues than in adjacent esophageal tissues (P < .01). IHC results showed that FN1 protein was expressed in both tumor cells and stroma. High expression of FN1 mRNA and FN1 protein in ESCC tumor tissues was significantly correlated with the depth of tumor invasion, lymph node metastasis and clinical stage of the tumor (P < .05). Survival analysis revealed that patients with higher FN1 mRNA and protein expression had significantly lower survival rates than those with lower FN1 mRNA or protein expression (P < .01). Multivariate cox regression analysis showed that high FN1 protein expression in ESCC tumor tissues was an independent risk factor for low survival in ESCC patients (P < .05). High expression of FN1 protein in ESCC tumor tissue is an independent poor prognostic factor. FN1 protein could be a potential target for the treatment of ESCC.

Use of imaging prediction model for omission of axillary surgery in early-stage breast cancer patients.

PURPOSE: To develop a prediction model incorporating clinicopathological information, US, and MRI to diagnose axillary lymph node (LN) metastasis with acceptable false negative rate (FNR) in patients with early stage, clinically node-negative breast cancers. METHODS: In this single center retrospective study, the inclusion criteria comprised women with clinical T1 or T2 and N0 breast cancers who underwent preoperative US and MRI between January 2017 and July 2018. Patients were temporally divided into the development and validation cohorts. Clinicopathological information, US, and MRI findings were collected. Two prediction models (US model and combined US and MRI model) were created using logistic regression analysis from the development cohort. FNRs of the two models were compared using the McNemar test. RESULTS: A total of 964 women comprised the development (603 women, 54 ± 11 years) and validation (361 women, 53 ± 10 years) cohorts with 107 (18%) and 77 (21%) axillary LN metastases in each cohort, respectively. The US model consisted of tumor size and morphology of LN on US. The combined US and MRI model consisted of asymmetry of LN number, long diameter of LN, tumor type, and multiplicity of breast cancers on MRI, in addition to tumor size and morphology of LN on US. The combined model showed significantly lower FNR than the US model in both development (5% vs. 32%, P < .001) and validation (9% vs. 35%, P < .001) cohorts. CONCLUSION: Our prediction model combining US and MRI characteristics of index cancer and LN lowered FNR compared to using US alone, and could potentially lead to avoid unnecessary SLNB in early stage, clinically node-negative breast cancers.

Pax6-induced proliferation and differentiation of bone marrow mesenchymal stem cells into limbal epithelial stem cells.

Corneal integrity, transparency, and visual acuity are maintained by corneal epithelial cells (CECs), which are continuously renewed by limbal epithelial stem cells (LESCs). The limbal stem cell deficiency (LSCD) is associated with ocular diseases. This study aimed to develop a novel method to differentiate bone marrow mesenchymal stem cells (BM-MSCs) into LESC-like cells using a culture medium and paired box 6 (Pax6) transfection. The LESC-like cells were confirmed using the LESC markers CK14 and p63 and CEC marker CK12. Pax6 induces BM-MSCs to differentiate into LESC-like cells in vitro. Mouse models of chemical corneal burn were obtained and treated with the LESC-like cells. The transplantation experiment indicated that Pax6-reprogramed BM-MSCs attached to and replenished the damaged cornea via the formation of stratified corneal epithelium. The proliferation and colony formation abilities of Pax6-overexpressing BM-MSCs were significantly enhanced. These findings provide evidence that BM-MSCs might serve as an excellent candidate for generating bioengineered corneal epithelium and provide a new strategy for the treatment of clinical corneal damage.

Axl alleviates DSS-induced colitis by preventing dysbiosis of gut microbiota.

Axl is a tyrosine kinase receptor, a negative regulator for innate immune responses and inflammatory bowel disease (IBD). The gut microbiota regulates intestinal immune homeostasis, but the role of Axl in the pathogenesis of IBD through the regulation of gut microbiota composition remains unresolved. In this study, mice with DSS-induced colitis showed increased Axl expression, which was almost entirely suppressed by depleting the gut microbiota with antibiotics. Axl-/- mice without DSS administration exhibited increased bacterial loads, especially the Proteobacteria abundant in patients with IBD, significantly consistent with DSS-induced colitis mice. Axl-/- mice also had an inflammatory intestinal microenvironment with reduced antimicrobial peptides and overexpression of inflammatory cytokines. The onset of DSS-induced colitis occurred faster with an abnormal expansion of Proteobacteria in Axl-/- mice than in WT mice. These findings suggest that a lack of Axl signaling exacerbates colitis by inducing aberrant compositions of the gut microbiota in conjunction with an inflammatory gut microenvironment. In conclusion, the data demonstrated that Axl signaling could ameliorate the pathogenesis of colitis by preventing dysbiosis of gut microbiota. Therefore, Axl may act as a potential novel biomarker for IBD and can be a potential candidate for the prophylactic or therapeutic target of diverse microbiota dysbiosis-related diseases.