Ultrasensitive and Rapid Circulating Tumor DNA Liquid Biopsy Using Surface-Confined Gene Amplification on Dispersible Magnetic Nano-Electrodes.

Circulating tumor DNA (ctDNA) detection has been acknowledged as a promising liquid biopsy approach for cancer diagnosis, with various ctDNA assays used for early detection and treatment monitoring. Dispersible magnetic nanoparticle-based electrochemical detection methods have been proposed as promising candidates for ctDNA detection based on the detection performance and features of the platform material. This study proposes a nanoparticle surface-localized genetic amplification approach by integrating Fe3O4-Au core-shell nanoparticles into polymerase chain reactions (PCR). These highly dispersible and magnetically responsive superparamagnetic nanoparticles act as nano-electrodes that amplify and accumulate target ctDNA in situ on the nanoparticle surface upon PCR amplification. These nanoparticles are subsequently captured and subjected to repetitive electrochemical measurements to induce reconfiguration-mediated signal amplification for ultrasensitive (∼3 aM) and rapid (∼7 min) metastatic breast cancer ctDNA detection in vitro. The detection platform can also detect metastatic biomarkers from in vivo samples, highlighting the potential for clinical applications and further expansion to rapid and ultrasensitive multiplex detection of various cancers.

Disrupted Rotational Perception During Simultaneous Stimulation of Rotation and Inertia.

Two vestibular signals, rotational and inertial cues, converge for the perception of complex motion. However, how vestibular perception is built on neuronal behaviors and decision-making processes, especially during the simultaneous presentation of rotational and inertial cues, has yet to be elucidated in humans. In this study, we analyzed the perceptual responses of 20 participants after pairwise rotational experiments, comprised of four control and four test sessions. In both control and test sessions, participants underwent clockwise and counterclockwise rotations in head-down and head-up positions. The difference between the control and test sessions was the head re-orientation relative to gravity after rotations, thereby providing only rotational cues in the control sessions and both rotational and inertial cues in the test sessions. The accuracy of perceptual responses was calculated by comparing the direction of rotational and inertial cues acquired from participants with that predicted by the velocity-storage model. The results showed that the accuracy of rotational perception ranged from 80 to 95% in the four control sessions but significantly decreased to 35 to 75% in the four test sessions. The accuracy of inertial perception in the test sessions ranged from 50 to 70%. The accuracy of rotational perception improved with repetitive exposure to the simultaneous presentation of both rotational and inertial cues, while the accuracy of inertial perception remained steady. The results suggested a significant interaction between rotational and inertial perception and implied that vestibular perception acquired in patients with vestibular disorders are potentially inaccurate.

Factors influencing the development of artificial intelligence in orthodontics.

OBJECTIVES: Since developing AI procedures demands significant computing resources and time, the implementation of a careful experimental design is essential. The purpose of this study was to investigate factors influencing the development of AI in orthodontics. MATERIALS AND METHODS: A total of 162 AI models were developed, with various combinations of sample sizes (170, 340, 679), input variables (40, 80, 160), output variables (38, 76, 154), training sessions (100, 500, 1000), and computer specifications (new vs. old). The TabNet deep-learning algorithm was used to develop these AI models, and leave-one-out cross-validation was applied in training. The goodness-of-fit of the regression models was compared using the adjusted coefficient of determination values, and the best-fit model was selected accordingly. Multiple linear regression analyses were employed to investigate the relationship between the influencing factors. RESULTS: Increasing the number of training sessions enhanced the effectiveness of the AI models. The best-fit regression model for predicting the computational time of AI, which included logarithmic transformation of time, sample size, and training session variables, demonstrated an adjusted coefficient of determination of 0.99. CONCLUSION: The study results show that estimating the time required for AI development may be possible using logarithmic transformations of time, sample size, and training session variables, followed by applying coefficients estimated through several pilot studies with reduced sample sizes and reduced training sessions.

Effectiveness of calcipotriol/betamethasone dipropionate aerosol foam in patients with small versus large plaque psoriasis in routine practice in South Korea.

Small plaque psoriasis is the typical form of chronic plaque psoriasis affecting adults in South Korea. The effectiveness of calcipotriol/betamethasone dipropionate (Cal/BD) aerosol foam for large and small psoriasis plaques has not previously been examined. We performed a post hoc analysis of a recent, 4-week observational study of Cal/BD aerosol foam use in routine clinical practice in South Korea. Investigator Global Assessment response ([IGA] 0/1 at week 4), Patient Global Assessment response ([PaGA] 0/1 at week 4), change in Psoriasis Area and Severity Index (PASI), changes in psoriasis symptom scores, change in the Dermatology Life Quality Index (DLQI), and the proportion of patients achieving DLQI ≤5 were analyzed for patients with small (≤5 cm; n = 131) or large (>5 cm; n = 35) baseline plaque size. IGA response rates were similar for patients with small and large plaques (59.5% and 51.4% respectively). Similarly, there was no significant difference between the small and large groups in mean change in PASI (-2.20 vs -3.34), the proportions of patients with DLQI ≤5 (62.3% vs 54.3%) or PaGA 0/1 (29.2% vs 40.0%). Mean improvements in DLQI (-4.04 vs -6.20) and in psoriasis symptoms including itching (-1.50 vs -2.83), sleep loss (-0.67 vs -1.89), dryness (-1.57 vs -2.97), scaling (-1.21 vs -3.57), and redness (-1.17 vs -3.11) were greater in patients with large plaques than those with small plaques. Itching and DLQI differences were not statistically significant after adjustment for baseline characteristics. Stratification by body surface area affected eliminated statistically significant differences between the groups for most outcomes. In conclusion, this analysis suggests that Cal/BD aerosol foam is an effective, well-accepted treatment for adult patients with the small plaques typical of chronic plaque psoriasis in South Korea, as well as for those with large plaques.

Longitudinal Comparative Analysis of Circulating Tumor DNA and Matched Tumor Tissue DNA in Patients with Metastatic Colorectal Cancer Receiving Palliative First-Line Systemic Anti-Cancer Therapy.

Purpose: This study aimed to compare tumor tissue DNA (ttDNA) and circulating tumor DNA (ctDNA) to explore the clinical applicability of ctDNA and to better understand clonal evolution in patients with metastatic colorectal cancer undergoing palliative first-line systemic therapy. Materials and Methods: We performed targeted sequencing analysis of 88 cancer-associated genes using germline DNA, ctDNA at baseline (baseline-ctDNA), and ctDNA at progressive disease (PD-ctDNA). The results were compared with ttDNA data. Results: Among 208 consecutively enrolled patients, we selected 84 (41 males; median age 59, range 35 to 90) with all four sample types available. A total of 202 driver mutations were found in 34 genes. ttDNA exhibited the highest mutation frequency (n=232), followed by baseline-ctDNA (n=155) and PD-ctDNA (n=117). Sequencing ctDNA alongside ttDNA revealed additional mutations in 40 patients (47.6%). PD-ctDNA detected 13 novel mutations in 10 patients (11.9%) compared to ttDNA and baseline-ctDNA. Notably, 7 mutations in 5 patients (6.0%) were missense or nonsense mutations in APC, TP53, SMAD4, and CDH1 genes. In baseline-ctDNA, higher maximal variant allele frequency (VAF) values (p=0.010) and higher VAF values of APC (p=0.012), TP53 (p=0.012), and KRAS (p=0.005) mutations were significantly associated with worse overall survival. Conclusion: While ttDNA remains more sensitive than ctDNA, our ctDNA platform demonstrated validity and potential value when ttDNA was unavailable. Post-treatment analysis of PD-ctDNA unveiled new pathogenic mutations, signifying cancer's clonal evolution. Additionally, baseline-ctDNA's VAF values were prognostic after treatment.

Reprogramming anchorage dependency to develop cell lines for recombinant protein expression.

As the biopharmaceutical industry continues to mature in its cost-effectiveness and productivity, many companies have begun employing larger-scale biomanufacturing and bioprocessing protocols. While many of these protocols require cells with anchorage-independent growth, it remains challenging to induce the necessary suspension adaptations in many different cell types. In addition, although transfection efficiency is an important consideration for all cells, especially for therapeutic protein production, cells in suspension are generally more difficult to transfect than adherent cells. Thus, much of the biomanufacturing industry is focused on the development of new human cell lines with properties that can support more efficient biopharmaceutical production. With this in mind, we identified a set of "Adherent-to-Suspension Transition" (AST) factors, IKZF1, BTG2 and KLF1, the expression of which induces adherent cells to acquire anchorage-independent growth. Working from the HEK293A cell line, we established 293-AST cells and 293-AST-TetR cells for inducible and reversible reprogramming of anchorage dependency. Surprisingly, we found that the AST-TetR system induces the necessary suspension adaptations with an accompanying increase in transfection efficiency and protein expression rate. Our AST-TetR system therefore represents a novel technological platform for the development of cell lines used for generating therapeutic proteins.

HSPA5 and FGFR1 genes in the mesenchymal subtype of glioblastoma can improve a treatment efficacy.

Tyrosine kinase inhibitors (TKIs) have emerged as a potential treatment strategy for glioblastoma multiforme (GBM). However, their efficacy is limited by various drug resistance mechanisms. To devise more effective treatments for GBM, genetic characteristics must be considered in addition to pre-existing treatments. We performed an integrative analysis with heterogeneous GBM datasets of genomic, transcriptomic, and proteomic data from DepMap, TCGA and CPTAC. We found that poor prognosis was induced by co-upregulation of heat shock protein family A member 5 (HSPA5) and fibroblast growth factor receptor 1 (FGFR1). Co-up regulation of these two genes could regulate the PI3K/AKT pathway. GBM cell lines with co-upregulation of these two genes showed higher drug sensitivity to PI3K inhibitors. In the mesenchymal subtype, the co-upregulation of FGFR1 and HSPA5 resulted in the most malignant subtype of GBM. Furthermore, we found this newly discovered subtype was correlated with homologous recombination deficiency (HRD) In conclusion, we discovered novel druggable candidates within the group exhibiting co-upregulation of these two genes in GBM, suggest potential strategies for combination therapy.

Airway management of a patient with Mounier-Kuhn syndrome during general anesthesia - A case report.

BACKGROUND: Mounier-Kuhn syndrome (MKS) is a rare disorder characterized by abnormal dilation of the trachea and main bronchi. MKS can be easily missed on chest X-rays, making diagnosis difficult. Under general anesthesia, challenges such as airway leakage or collapse during mechanical ventilation may complicate the achievement of adequate tidal volumes. CASES: A 94-year-old woman requiring emergency hemiarthroplasty of the hip under general anesthesia was admitted. Preoperative chest X-rays revealed dilation of the trachea and main bronchi, but the patient exhibited no respiratory symptoms. We diagnosed her with MKS and opted for an 8.0-mm-inner-diameter reinforced tracheal tube. We positioned the cuff in the subglottic area, inflating it while monitoring for air leakage. Throughout the surgery, adequate tidal volume was maintained. CONCLUSIONS: Anesthesiologists must conduct a comprehensive evaluation of patients with MKS, including a review of chest radiographs, and establish a meticulous anesthesia plan prior to surgery.

Differential predictors of early- and delayed-onset post-traumatic stress disorder following physical injury: a two-year longitudinal study.

Objectives: This study aimed to investigate the predictors of both early- and delayed-onset PTSD over a 2-year period following physical injuries. Methods: Patients were recruited from a trauma center at a university hospital in South Korea (June 2015 ~ January 2021). At baseline, 1142 patients underwent comprehensive assessments including socio-demographic, pre-trauma, trauma-related, and peri-trauma evaluations. Diagnoses of acute stress disorder (ASD) and subthreshold ASD were also determined using the Clinician-administered PTSD Scale (CAPS). Follow-up assessments at three months included diagnoses of PTSD and subthreshold PTSD using CAPS, and stressful life events (SLEs), with additional evaluations at 6, 12, and 24 months. The analyzed sample comprised 1014 patients followed up at least once after the baseline and 3-month evaluations. PTSD diagnoses were categorized into early-onset (within the first six months after trauma) and delayed-onset (more than six months after trauma). Logistic regression models identified predictors for each group. Results: Early-onset and delayed-onset PTSD were diagnosed in 79 and 35 patients, respectively. Early-onset PTSD was predicted by previous psychiatric disorders, previous traumatic events, ASD and subthreshold ASD diagnoses, and higher anxiety levels. In contrast, delayed-onset PTSD was linked to higher education, higher injury severity, and subthreshold PTSD and SLEs at 3-month follow-up. Conclusion: Distinct predictors were found for early-onset and delayed-onset PTSD. The findings underscore the heterogeneous factors influencing the temporal development of PTSD post-trauma, and may provide valuable guidance for more targeted interventions and improved patient outcomes.

Mitigating substrate effects of van der Waals semiconductors using perfluoropolyether self-assembled monolayers.

The properties of transition metal dichalcogenides (TMDCs) are critically dependent on the dielectric constant of substrates, which significantly limits their application. To address this issue, we used a perfluorinated polyether (PFPE) self-assembled monolayer (SAM) with low surface energy to increase the van der Waals (vdW) gap between TMDCs and the substrate, thereby reducing the interaction between them. This resulted in a reduction in the subthreshold swing value, an increase in the photoluminescence intensity of excitons, and a decrease in the doping effect by the substrate. This work will provide a new way to control the TMDC/dielectric interface and contribute to expanding the applicability of TMDCs.

Medication-related incidents in acute care hospitals among different age groups: An analysis of national patient safety report data.

PURPOSE: This study aimed to perform a nationwide analysis of medication errors (MEs) from hospitals using national reporting system data and to compare the ME patterns among different age groups. METHODS: We analyzed medication-related incidents in acute care hospitals reported to the Korean Patient Safety Reporting and Learning System (KOPS), which is a patient safety reporting system, from July 2016 to December 2020. The stages of the medication use process, type of errors, medication class involved in MEs, and degree of harm were analyzed. RESULTS: Among a total of 5071 medication-related incidents, 37.7% (1911 cases) were incidents that caused patient harm and 1.2% caused long-term, permanent, and fatal harm. The proportion of medication-related incidents that resulted in harm was the highest among the <1-year-old age group (67 cases, 51.5%), followed by the elderly (≥ 65 years) (828 cases, 40.9%). The cases leading to patient death were most frequently reported in patients aged ≥65 years. Medication-related incidents occurred mainly in the administration stage (2954 cases, 58.3%), and wrong dose was the most frequently reported ME type. The most prevalent medication class occurring in the 20-64-year age group (256 cases, 11.7%) was 'antibacterials for systemic use', whereas 'contrast media' (236 cases, 11.6%) and 'blood substitutes and perfusion solutions' (98 cases, 19.3%) were the most prevalent drug classes in the ≥65- and <20-year-old age groups, respectively. CONCLUSIONS: It is necessary to establish guidelines for the prevention of medication-related incidents according to the medication use process and patient age group.

The use of the internal transcribed spacer region for phylogenetic analysis of the microsporidian parasite Enterocytozoon hepatopenaei infecting whiteleg shrimp (Penaeus vannamei) and for the development of a nested PCR as its diagnostic tool.

The increasing economic losses associated with growth retardation caused by Enterocytozoon hepatopenaei (EHP), a microsporidian parasite infecting penaeid shrimp, require effective monitoring. The internal transcribed spacer (ITS)-1 region, the non-coding region of ribosomal clusters between 18S and 5.8S rRNA genes, is widely used in phylogenetic studies due to its high variability. In this study, the ITS-1 region sequence (~600-bp) of EHP was first identified, and primers for a polymerase chain reaction (PCR) assay targeting that sequence were designed. A newly developed nested-PCR method successfully detected the EHP in various shrimp (Penaeus vannamei and P. monodon) and related samples, including water and feces collected from Indonesia, Thailand, South Korea, India, and Malaysia. The primers did not cross-react with other hosts and pathogens, and this PCR assay is more sensitive than existing PCR detection methods targeting the small subunit ribosomal RNA (SSU rRNA) and spore wall protein (SWP) genes. Phylogenetic analysis based on the ITS-1 sequences indicated that the Indonesian strain was distinct (86.2%) from other strains collected from Thailand and South Korea, and also showed the internal diversity among Thailand (N = 7, divided into four branches) and South Korean (N = 5, divided into two branches) samples. The results revealed the ability of the ITS-1 region to determine the genetic diversity of EHP from different geographical origins.

Distinct effects of rosuvastatin and rosuvastatin/ezetimibe on senescence markers of CD8+ T cells in patients with type 2 diabetes mellitus: a randomized controlled trial.

Objectives: Chronic low-grade inflammation is widely recognized as a pathophysiological defect contributing to ß-cell failure in type 2 diabetes mellitus (T2DM). Statin therapy is known to ameliorate CD8+ T cell senescence, a mediator of chronic inflammation. However, the additional immunomodulatory roles of ezetimibe are not fully understood. Therefore, we investigated the effect of statin or statin/ezetimibe combination treatment on T cell senescence markers. Methods: In this two-group parallel and randomized controlled trial, we enrolled 149 patients with T2DM whose low-density lipoprotein cholesterol (LDL-C) was 100 mg/dL or higher. Patients were randomly assigned to either the rosuvastatin group (N=74) or the rosuvastatin/ezetimibe group (N=75). The immunophenotype of peripheral blood mononuclear cells and metabolic profiles were analyzed using samples from baseline and post-12 weeks of medication. Results: The fractions of CD8+CD57+ (senescent CD8+ T cells) and CD4+FoxP3+ (Treg) significantly decreased after intervention in the rosuvastatin/ezetimibe group (-4.5 ± 14.1% and -1.2 ± 2.3%, respectively), while these fractions showed minimal change in the rosuvastatin group (2.8 ± 9.4% and 1.4 ± 1.5%, respectively). The degree of LDL-C reduction was correlated with an improvement in HbA1c (R=0.193, p=0.021). Changes in the CD8+CD57+ fraction positively correlated with patient age (R=0.538, p=0.026). Notably, the fraction change in senescent CD8+ T cells showed no significant relationship with changes in either HbA1c (p=0.314) or LDL-C (p=0.592). Finally, the ratio of naïve to memory CD8+ T cells increased in the rosuvastatin/ezetimibe group (p=0.011), but not in the rosuvastatin group (p=0.339). Conclusions: We observed a reduction in senescent CD8+ T cells and an increase in the ratio of naive to memory CD8+ T cells with rosuvastatin/ezetimibe treatment. Our results demonstrate the immunomodulatory roles of ezetimibe in combination with statins, independent of improvements in lipid or HbA1c levels.

Exploratory Clinical Trial of a Depression Diagnostic Software That Integrates Stress Biomarkers and Composite Psychometrics.

OBJECTIVE: This study evaluated the clinical effectiveness of Minds.NAVI, a depression screening kit combining psychometric measures and stress hormone biomarkers, in a prospective clinical trial. The objective was to assess its potential as a depression screening tool and investigate the associations between psychological assessments, salivary hormone staging, and depression severity. METHODS: Thirty-five participants with major depressive disorder and 12 healthy controls (HCs) were included. The Minds.NAVI software, utilizing the PROtective and Vulnerable factors battEry Test (PROVE) and salivary cortisol/dehydroepiandrosterone (DHEA) analysis, was employed. The PROVE test is a comprehensive self-report questionnaire that assesses depressive symptoms, suicide risk, attachment style, adverse childhood experiences, mentalization capacity, and resilience. In addition, salivary cortisol and DHEA levels were measured to evaluate the functional stage of the hypothalamic-pituitary-adrenal (HPA) axis. RESULTS: Minds.NAVI exhibited 100% sensitivity, 91.7% specificity, and 97.9% accuracy in distinguishing depression from HCs within an exploratory small group. Salivary stress hormone phases showed changes with depression stage (p=0.030), and the proportion of patients with "adrenal exhaustion stage" was higher in the moderate/severe depression group (p=0.038). Protective/vulnerable factors differed significantly between controls and depressed groups (p<0.001). Cortisol awakening response inversely correlated with depressive symptom severity (r=-0.31, p=0.034). CONCLUSION: This study suggested possible clinical effectiveness of Minds.NAVI, a depression screening tool that integrates psychometric measures and stress hormone biomarkers. The findings support the potential association between depression, chronic stress, and HPA axis hyporesponsiveness.

How to Safely Use the Perforator-based Keystone Island Flap in the Scalp: Basal Cell Carcinoma of the Scalp With Local Invasion to Calvarium.

Scalp reconstruction has always been a challenging problem for even the most experienced surgeon to provide good aesthetic and functional results. This is mainly because the scalp is less mobile and tight, requiring a much larger dissection for the size of the original defect. We hypothesized that the omega variant perforator-based keystone island flap at the subgaleal plane provides a versatile and easily reproducible reconstructive option for scalp reconstruction after wide skin cancer excision. We reviewed all patients who underwent reconstruction with the keystone flap or its modification to repair scalp defects following wide resection of skin cancer in the scalp abutting calvarium from May 2021 to July 2023. We designed the flap width 50% wider than original keystone flap design first introduced by Dr. Behan. We reconstructed medium- to large-sized scalp defects ranging from 2×2 to 5×5 cm2 using an omega variant perforator-based keystone island flap. All patients were satisfied with the aesthetic outcomes without complications. Keystone flaps are a versatile option for reconstructing the scalp after cancer resection. This strategy obviates the need for skin grafting, myocutaneous flap or free flap after cancer removal in the scalp.

Antibiotic resistance in livestock, environment and humans: One Health perspective.

Antibiotic resistance (AR) is a complex, multifaceted global health issue that poses a serious threat to livestock, humans, and the surrounding environment. It entails several elements and numerous potential transmission routes and vehicles that contribute to its development and spread, making it a challenging issue to address. AR is regarded as an One Health issue, as it has been found that livestock, human, and environmental components, all three domains are interconnected, opening up channels for transmission of antibiotic resistant bacteria (ARB). AR has turned out to be a critical problem mainly because of the overuse and misuse of antibiotics, with the anticipation of 10 million annual AR-associated deaths by 2050. The fact that infectious diseases induced by ARB are no longer treatable with antibiotics foreshadows an uncertain future in the context of health care. Hence, the One Health approach should be emphasized to reduce the impact of AR on livestock, humans, and the environment, ensuring the longevity of the efficacy of both current and prospective antibiotics.

Complete genome sequence of Enterococcus faecium strain AK_C_05 with potential characteristics applicable in livestock industry.

The Enterococcus faecium (E. faecium) strain AK_C_05 was isolated from cheonggukjang, the Korean traditional food, collected from a local market in South Korea. In this report, we presented the complete genome sequence of E. faecium strain AK_C_05. The genome of E. faecium strain AK_C_05 genome consisted of one circular chromosome (2,691,319 bp) with a guanine + cytosine (GC) content of 38.3% and one circular plasmid (177,732 bp) with a GC content of 35.48%. The Annotation results revealed 2,827 protein-coding sequences (CDSs), 18 rRNAs, and 68 tRNA genes. It possesses genes, which encodes enzymes such as alpha-galactosidase (EC 3.2.1.22), beta-glucosidase (EC 3.2.1.21) and alpha-L-arabinofuranosidase (EC 3.2.1.55) enabling efficient utilization of carbohydrates. Based on Clusters of Orthologous Groups analysis, E. faecium strain AK_C_05 showed specialization in carbohydrate transport and metabolism indicating the ability to generate energy using a variety of carbohydrates.

Moderating role of functioning level on the association between suicidal ideation and delayed-onset post-traumatic stress disorder.

OBJECTIVES: This study aimed to investigate the relationship between suicidal ideation at baseline and the development of post-traumatic stress disorder (PTSD) in individuals who have experienced physical injuries, with a specific focus on how this relationship is moderated by the patient's functioning level. METHODS: Participants were consecutively recruited from a trauma center and prospectively followed for two years. At baseline, suicidal ideation was assessed using the Brief Psychiatric Rating Scale, and functioning level was evaluated using the Social and Occupational Functioning Assessment Scale. During the follow-up, PTSD diagnosis was established using the Clinician-Administered PTSD Scale for DSM-5. Binary and multinomial logistic regression analyses were employed to examine the associations between suicidal ideation, functioning level, and PTSD. RESULTS: Of the 1014 participants analyzed, 114 (11.2%) developed PTSD, with early-onset observed in 79 (7.8%) and delayed-onset in 35 (3.5%) cases. Suicidal ideation at baseline was significantly associated with both early- and delayed-onset PTSD. Notably, higher functioning individuals with baseline suicidal ideation had an increased likelihood of developing delayed-onset PTSD, while this association was not significant in lower functioning individuals, with significant interaction terms. Additionally, suicidal ideation was a consistent predictor of early-onset PTSD across all functioning levels. CONCLUSION: The impact of baseline suicidal ideation on PTSD varies depending on the individual's functioning level, with higher functioning individuals being more vulnerable to delayed-onset PTSD. These findings underscore the importance of considering functional status in the assessment and intervention of PTSD following physical trauma.

Investigating ischemia and reperfusion-induced organ damage in severe cardiac arrest: A comprehensive proteomics perspective.

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Novel microbiota Mesosutterella faecium sp. nov. has a protective effect against inflammatory bowel disease.

A novel Gram-negative, obligate anaerobe, non-motile, flagella-lacking, catalase- and oxidase-negative, coccobacilli-shaped bacterial strain designated AGMB02718T was isolated from swine feces. The 16S rRNA gene analysis indicated that strain AGMB02718T belonged to the genus Mesosutterella with the highest similarity to M. multiformis 4NBBH2T (= DSM 106860T) (sequence similarity of 96.2%), forming a distinct phylogenetic lineage. Its growth occurred at 25-45°C (optimal 37°C) and in 0.5-1% NaCl (optimal 0.5%). Strain AGMB02718T was asaccharolytic and contained menaquinone 6 (MK-6) and methylmenaquinone 6 (MMK-6) as the predominant respiratory quinones. The major cellular fatty acids in the isolate were C18:1ω9c and C16:0. Based on the whole-genome sequencing analysis, strain AGMB02718T had a 2,606,253 bp circular chromosome with a G + C content of 62.2%. The average nucleotide identity value between strain AGMB02718T and M. multiformis 4NBBH2T was 72.1%, while the digital DNA-DNA hybridization value was 20.9%. Interestingly, genome analysis suggested that strain AGMB02718T possessed a low-toxicity lipopolysaccharide (LPS) because the genome of the isolate does not include lpxJ and lpxM genes for Kdo2-Lipid A (KLA) assembly, which confers high toxicity to LPS. Moreover, in vitro macrophage stimulation assay confirmed that AGMB02718T produced LPS with low toxicity. Because the low-toxicity LPS produced by the Sutterellaceae family is involved in regulating host immunity and low-toxicity LPS-producing strains can help maintain host immune homeostasis, we evaluated the anti-inflammatory activity of strain AGMB02718T against inflammatory bowel disease (IBD). As a result, strain AGMB02718T was able to prevent the inflammatory response in a dextran sulfate sodium (DSS)-induced colitis model. Therefore, this strain represents a novel species of Mesosutterella that has a protective effect against DSS-induced colitis, and the proposed name is Mesosutterella faecium sp. nov. The type strain is AGMB02718T (=GDMCC 1.2717T = KCTC 25541T).