Association between Breakfast Consumption Frequency and Chronic Inflammation in Korean Adult Males: Korea National Health and Nutrition Examination Survey 2016-2018.

Background: Skipping breakfast is associated with an increased risk of chronic inflammatory diseases. This study aimed to examine the association between breakfast-eating habits and inflammation, using high-sensitivity C-reactive protein (hs-CRP) as a marker. Methods: A total of 4,000 Korean adult males with no history of myocardial infarction, angina, stroke, diabetes, rheumatoid arthritis, cancer, or current smoking were included. Data from the 2016-2018 Korea National Health and Nutrition Examination Survey were used for analysis. The frequency of breakfast consumption was assessed through a questionnaire item in the dietary survey section asking participants about their weekly breakfast consumption routines over the past year. Participants were categorized into two groups, namely "0-2 breakfasts per week" and "3-7 breakfasts per week"; hs-CRP concentrations were measured through blood tests. Results: Comparing between the "infrequent breakfast consumption (0-2 breakfasts per week)" and "frequent breakfast consumption (3-7 breakfasts per week)" groups, the mean hs-CRP was found to be significantly higher in the "infrequent breakfast consumption" group, even after adjusting for age, body mass index, physical activity, alcohol consumption, systolic blood pressure, blood pressure medication, fasting blood glucose, and triglycerides (mean hs-CRP: frequent breakfast consumption, 1.36±0.09 mg/L; infrequent breakfast consumption, 1.17±0.05 mg/L; P-value=0.036). Conclusion: Less frequent breakfast consumption was associated with elevated hs-CRP levels. Further large-scale studies incorporating adjusted measures of daily eating patterns as well as food quality and quantity are required for a deeper understanding of the role of breakfast in the primary prevention of chronic inflammatory diseases.

Deep learning model using stool pictures for predicting endoscopic mucosal inflammation in patients with ulcerative colitis.

OBJECTIVES: Stool characteristics may change depending on the endoscopic activity of ulcerative colitis (UC). We developed a deep learning model using stool photos of patients with UC (DLSUC) to predict endoscopic mucosal inflammation. METHODS: This was a prospective multicenter study conducted in six tertiary referral hospitals. Patients scheduled to undergo endoscopy for mucosal inflammation monitoring were asked to take photos of their stool using smartphones within 1 week before the day of endoscopy. DLSUC was developed using 2161 stool pictures from 306 patients and tested on 1047 stool images from 126 patients. The ulcerative colitis endoscopic index of severity (UCEIS) was used to define endoscopic activity. The performance of DLSUC in endoscopic activity prediction was compared with that of fecal calprotectin (Fcal). RESULTS: The area under the receiver operating characteristic curve (AUC) of DLSUC for predicting endoscopic activity was 0.801 (95% confidence interval [CI] 0.717-0.873), which was not statistically different from the AUC of Fcal (0.837 [95% CI, 0.767-0.899, DeLong's P=0.458]). When rectal sparing cases (23/126, 18.2%) were excluded, the AUC of DLSUC increased to 0.849 (95% CI, 0.760-0.919). The accuracy, sensitivity, and specificity of DLSUC in predicting endoscopic activity were 0.746, 0.662, and 0.877 in all patients and 0.845, 0.745, and 0.958 in patients without rectal sparing, respectively. Active patients classified by DLSUC were more likely to experience disease relapse during a median 8-month follow-up (log-rank test, P=0.002). CONCLUSIONS: DLSUC demonstrated a good discriminating power similar to that of Fcal in predicting endoscopic activity with improved accuracy in patients without rectal sparing. This study implies that stool photos are a useful monitoring tool for typical UC.

Neuron-Specific Enolase as a Predictor of Neurologic Outcomes in Extracorporeal Cardiopulmonary Resuscitation Patients.

Background: Neuron-specific enolase (NSE) has traditionally been used as a biomarker to predict neurologic outcomes after cardiac arrest. This study aimed to evaluate the utility of NSE in predicting neurologic outcomes in patients undergoing extracorporeal cardiopulmonary resuscitation (ECPR). Methods: This observational cohort study included 47 consecutive adult ECPR patients (median age, 59.0 years; 74.5% males) treated between January 2018 and December 2021 at a tertiary extracorporeal life support center. The primary outcome was a poor neurologic outcome, defined as a Cerebral Performance Category score of 3-5 at hospital discharge. Results: Twelve (25.5%) patients had abnormal findings on computed tomography of the brain. A poor neurologic outcome was demonstrated in 22 (46.8%) patients. The NSE level at 72 h after ECPR showed the best prediction power for a poor neurologic outcome compared with NSE at 24 and 48 h. A cutoff value exceeding 61.9 µg/L for NSE at 72 h yielded an area under the curve (AUC) of 0.791 for predicting poor neurologic outcomes and exceeding 62.1 µg/L with an AUC of 0.838 for 30-day mortality. Conclusions: NSE levels at 72 h after ECPR appear to be a reliable biomarker for predicting poor neurologic outcomes and 30-day mortality in ECPR patients.

Use of colloids and crystalloids for perioperative clinical infusion management in cardiac surgery patients and postoperative outcomes: a meta-analysis.

BACKGROUND: The optimal fluid management strategy for patients undergoing cardiac surgery was controversial regarding fluid volume and intraoperative fluid types. This study aimed to assess the correlation between colloids and crystalloids used for perioperative fluid therapy in cardiac surgery patients and postoperative prognosis. METHODS: The Ovid MEDLINE(R) ALL, Embase, and Cochrane Central Register of Controlled Trials databases were searched for eligible studies on fluid management strategies using colloids and crystalloids for cardiac surgery patients published before August 25th, 2023. RESULTS: Ten randomized controlled trials met the eligibility criteria. Compared to the use of crystalloids, the use of colloids, including hydroxyethyl starch (HES), albumin, and gelatine, did not show any differences in mortality, transfusion, acute kidney injury, and atrial fibrillation rates, postoperative blood loss, the length of hospital stay, or the length of intensive care unit (ICU) stay. The results of this meta-analysis showed that the crystalloid group had significantly reduced postoperative chest tube output compared to the colloid group. In the subgroup analysis, the amount of fresh frozen plasma (FFP) infused was significantly lower when using fluid management in the ICU and when using isotonic crystalloids compared to the colloids. In addition, when using fluid management in the ICU, patients in the colloid group had a significant increase in urine volume 24 h after surgery. However, other related factors, including the type of crystalloid solution, type of colloidal solution, and timing of liquid management, did not affect most outcomes. CONCLUSION: Both colloids and crystalloids could be used as alternatives for perioperative fluid management after cardiac surgery. The use of crystalloids significantly reduced the postoperative chest tube output, and the need for FFP infusion decreased significantly with the use of isotonic crystalloids or fluid management during the ICU stay. ICU patients in the colloid group had higher urine output 24 h after surgery. In addition, although the infusion method was not related to most outcomes, the rates of red blood cell and FFP transfusion and postoperative blood loss in the crystalloid group seemed to be lower, which needed to be further studied in high-quality and large-sample RCTs. TRIAL REGISTRATION: PROSPERO, CRD42023415234.

A review of 280 nasopharyngeal tuberculosis cases and the effectiveness of antituberculosis treatments.

Objectives: Nasopharyngeal tuberculosis is a rare form of tuberculosis in which Mycobacterium tuberculosis infects the nasopharyngeal tissue. In this study, we analyzed key clinical features to prevent misdiagnosis and to raise awareness of the condition, while recommending suitable treatments. We also report a case of nasopharyngeal tuberculosis presenting with nasal congestion and intermittent ear fullness, contributing valuable educational insight for diagnosis. Methods: Demographic and clinical data from patients with nasopharyngeal tuberculosis were collected from PubMed, Embase, Web of Science and the Cochrane Central Register of Controlled Trials up to September 2022. In total, 280 patients from 69 studies were analyzed. Results: Reports indicate that the incidence of nasopharyngeal tuberculosis has doubled every decade, particularly in Asia. Most patients are female, presenting with granulomatous pathology and findings such as masses, lymphoid hyperplasia, polypoid formations, or swelling on endoscopic examination. Common symptoms include nasal obstruction, hearing impairment, sore throat, and dysphagia, usually accompanied by cervical lymphadenopathy. The mean duration from symptom onset to diagnosis is ∼2.88 months, and the average time from the start of treatment to resolution of symptoms is âˆ¼ 4.90 months. The antituberculosis treatment regimen and duration are significantly associated with the time to resolution (r = -0.648, p = 0.003 and r = 0.584, p = 0.028, respectively). Conclusion: These results suggest that an extended regimen of antituberculosis drugs may expedite symptom relief. However, there is a need for more standardized data on patient outcomes and treatment efficacy due to the current lack of comprehensive data.

Efficacy and safety of antibody-drug conjugates in the treatment of urothelial cell carcinoma: a systematic review and meta-analysis of prospective clinical trials.

Introduction: Urothelial carcinoma (UC) is a refractory disease for which achieving satisfactory outcomes remains challenging with current surgical interventions. Antibody-drug conjugates (ADCs) are a novel class of targeted therapeutics that have demonstrated encouraging results for UC. Although there is a limited number of high-quality randomized control trials (RCTs) examining the use of ADCs in patients with UC, some prospective non-randomized studies of interventions (NRSIs) provide valuable insights and pertinent information. We aim to assess the efficacy and safety of ADCs in patients with UC, particularly those with locally advanced and metastatic diseases. Methods: A systematic search was conducted across PubMed, Embase, the Cochrane Library, and Web of Science databases to identify pertinent studies. Outcomes, such as the overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), adverse events (AEs), and treatment-related adverse events (TRAEs), were extracted for further analyses. Results: Twelve studies involving 1,311 patients were included in this meta-analysis. In terms of tumor responses, the pooled ORR and DCR were 40% and 74%, respectively. Regarding survival analysis, the pooled median PFS and OS were 5.66 months and 12.63 months, respectively. The pooled 6-month PFS and OS were 47% and 80%, while the pooled 1-year PFS and OS were 22% and 55%, respectively. The most common TRAEs of the ADCs were alopecia (all grades: 45%, grades ≥ III: 0%), decreased appetite (all grades: 34%, grades ≥ III: 3%), dysgeusia (all grades: 40%, grades ≥ III: 0%), fatigue (all grades: 39%, grades ≥ III: 5%), nausea (all grades: 45%, grades ≥ III: 2%), peripheral sensory neuropathy (all grades: 37%, grades ≥ III: 2%), and pruritus (all grades: 32%, grades ≥ III: 1%). Conclusion: The meta-analysis in this study demonstrates that ADCs have promising efficacies and safety for patients with advanced or metastatic UC. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42023460232.

Light-induced ß-hydroxy sulfone synthesis in DNA-encoded libraries.

We here describe a visible-light photooxidation of sulfinate salts with common alkenes to yield ß-hydroxy sulfones on DNA. This process demonstrates a broad substrate compatibility and achieves conversion rates ranging from moderate to excellent. Most importantly, it presents a straightforward, efficient, and metal-free approach for synthesizing Csp3-rich DNA-encoded libraries.

Non-Clinical Safety Evaluation of Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells in Cynomolgus Monkeys.

Purpose: In recent years, exosomes have been proved to be used to treat many diseases. However, due to the lack of uniform quality control standards for exosomes, the safety of exosomes is still a problem to be solved, especially now more and more exosomes are used in clinical trials, and its non-clinical safety evaluation is particularly important. However, there is no safety evaluation standard for exosomes at present. Therefore, this study will refer to the evaluation criteria of therapeutic biological products, adopt non-human primates to evaluate the non-clinical safety of human umbilical cord mesenchymal stem cell exosomes from the general pharmacology and immunotoxicity, aiming at establishing a safety evaluation system of exosomes and providing reference for the clinical application of exosomes in the future. Methods: 3.85 × 1012 exosomes derived from human umbilical cord mesenchymal stem cells were injected into cynomolgus monkeys intravenously. The changes of general clinical conditions, hematology, immunoglobulin, Th1/Th2 cytokines, T lymphocytes and B lymphocytes, and immune organs were observed before and within 14 days after injection. Results: The results showed that exosomes did not have obvious pathological effects on the general clinical conditions, blood, coagulation function, organ coefficient, immunoglobulin, Th1/Th2 cytokines, lymphocytes, major organs, and major immune organs (spleen, thymus, bone marrow) of cynomolgus monkeys. However, the number of granulocyte-macrophage colonies in exosomes group was significantly higher than that in control group. Conclusion: To sum up, the general pharmacological results and immunotoxicity results showed that the injection of 3.85 × 1012 exosomes may have no obvious adverse reactions to cynomolgus monkeys. This dose of exosomes is relatively safe for treatment, which provides basis research for non-clinical safety evaluation of exosomes and provides reliable research basis for future clinical application of exosomes.

Positional obstructive sleep apnea and periodic limb movement during sleep: A large multi-center study.

Objectives: The relationships among positional obstructive sleep apnea (POSA), obstructive sleep apnea (OSA), and periodic limb movement during sleep (PLMS) are unclear. We analyzed these relationships according to OSA severity and explored the underlying mechanisms. Methods: We retrospectively reviewed 6,140 eligible participants who underwent full-night diagnostic polysomnography in four clinical centers over a period of 5 years with eventsynchronized analysis. The PLMS index (PLMI) and periodic limb movements with arousal index (PLMAI) were evaluated. The effects of POSA on the PLMI, PLMAI, and PLMS were analyzed according to OSA severity. Results: The mean PLMI and PLMAI, as well as PLMS prevalence, were significantly lower in those with severe OSA than in those with mild and moderate OSA. The mean PLMI was higher in mild OSA group than in control group. The mean PLMI (4.80 ± 12.71 vs. 2.59 ± 9.82 events/h, p < 0.001) and PLMAI (0.89 ± 3.66 vs. 0.53 ± 3.33 events/h, p < 0.001), and the prevalence of PLMS (11% vs. 5.3%, p < 0.001) were higher in patients with POSA than patients with non-POSA. This trend was particularly marked in severe OSA group (OR 1.55, 95%CI [1.07-2.27]) and less so in mild (OR 0.56, 95%CI [0.30-1.03]) and moderate (OR 1.82, 95%CI [0.99-3.34]) OSA groups. Conclusion: The POSA group tended to have a higher prevalence of PLMS, particularly in those with severe OSA. If PLMS is prominent, diagnosis and treatment of POSA and OSA may be considered.

Innovative On-DNA Synthesis of Sulfides and Sulfoximines: Enriching the DEL Synthesis Toolbox.

DNA-encoded library (DEL) technologies enable the fast exploration of gigantic chemical space to identify ligands for the target protein of interest and have become a powerful hit finding tool for drug discovery projects. However, amenable DEL chemistry is restricted to a handful of reactions, limiting the creativity of drug hunters. Here, we describe a new on-DNA synthetic pathway to access sulfides and sulfoximines. These moieties, usually contemplated as challenging to achieve through alkylation and oxidation, can now be leveraged in routine DEL selection campaigns.

Self-screening questionnaire for perianal fistulizing disease in patients with Crohn's disease.

BACKGROUND/AIMS: A poor prognostic factor for Crohn's disease (CD) includes perianal fistulizing disease, including perianal fistula and/or perianal abscess. Currently, a tool to assess perianal symptoms in patients with CD remains nonexistent. This study aimed to develop a perianal fistulizing disease self-screening questionnaire for patients with CD. METHODS: This prospective pilot study was conducted at three tertiary referral centers between January 2019 and May 2020. We formulated questions on perianal symptoms, including tenesmus, anal discharge, bleeding, pain, and heat. A 4-point Likert scale was used to rate each question. Patients with CD completed a questionnaire and underwent pelvic magnetic resonance imaging (MRI). RESULTS: Overall, 93 patients were enrolled, with 51 (54.8%) diagnosed with perianal fistulizing disease, as determined by pelvic MRI. The Spearman correlation findings demonstrated that anal pain (p = 0.450, p < 0.001) and anal discharge (p = 0.556, p < 0.001) were the symptoms that most significantly correlated with perianal disease. For anal pain and discharge, the area under the receiver operating characteristic curve of the scores was significantly higher than that of the combined score for all five symptoms (0.855 vs. 0.794, DeLong's test p = 0.04). For the two symptoms combined, the sensitivity, specificity, and positive predictive and negative predictive values were 88.2, 73.8, 80.4, and 83.8%, respectively, with 81.7% accuracy for detecting perianal fistulizing disease. CONCLUSION: This study indicates that simple questions regarding anal pain and discharge can help accurately identify the presence of perianal fistulizing disease in patients with CD.

Antibody-Conjugated Nanogel with Two Immune Checkpoint Inhibitors for Enhanced Cancer Immunotherapy.

Cancer immunotherapy by immune checkpoint inhibitors (ICIs) acts on antitumor responses by stimulating the immune system to attack cancer cells. However, this powerful therapy is hampered by its high treatment cost and limited efficacy. Here, it is shown that the development of an antibody-conjugated nanogel (ANGel), consisting of N-isopropylacrylamide-co-acrylic acid and antibody-binding protein (protein A), potentiates the efficacy of two ICI monoclonal antibodies (mAbs) (cytotoxic-T-lymphocyte-associated antigen 4 and programmed death ligand-1 mAbs). Compared with mAb treatment alone, treatment with a bispecific ANGel surface-conjugated with the mAbs significantly decreases both the survival of Michigan Cancer Foundation-7 (MCF-7) and M D Anderson-Metastatic Breast-231 (MDA-MB-231) breast cancer cells in vitro and the burden of 4T1-luciferase-2-derived orthotopic syngeneic tumors in vivo. The bispecific ANGel is also more potent than the conventional treatment at prolonging survival in animals with triple-negative breast cancer. The advantage of the bispecific ANGel over other engineered bispecific antibodies arises not only from the adaptability to link multiple antibodies quickly and easily, but also from the capability to maintain the anticancer effect steadily at subcutaneously delivered tumor site. This finding has an important implication for cancer immunotherapy, opening a new paradigm to treat solid tumors.

Prevalence and Associations Between Metabolic Syndrome Components and Hyperuricemia by Race: Findings From US Population, 2011-2020.

OBJECTIVE: We explored the trend in prevalence of hyperuricemia and metabolic syndrome in US populations and investigated associations between components of metabolic syndrome and hyperuricemia by race. METHODS: We analyzed data from the four most recent National Health and Nutrition Examination Survey (NHANES) cycles (2011 to March 2020), comprising 10,175 participants. Hyperuricemia is defined as serum urate >7.0 mg/dL (men) or >5.7 mg/dL (women), following the NHANES-III guideline. The definition of metabolic syndrome follows the National Cholesterol Education Program's Adult Treatment Panel III guideline. We estimated the prevalence of metabolic syndrome and hyperuricemia in each cycle and performed subgroup analyses with logistic regression to investigate the patterns of associated components of metabolic syndrome with hyperuricemia. RESULTS: In the most recent cycle (2017 to March 2020), the prevalence of metabolic syndrome was 45.9% and that of hyperuricemia was 20.7%. Over the 2011 to 2020 period, a significant rise in metabolic syndrome prevalence was observed among Hispanic and Asian populations, and the prevalence of hyperuricemia has increased significantly only in the Hispanic population. After adjustment for confounding factors, patients with metabolic syndrome exhibited a higher hyperuricemia in women than in men. Elevated blood pressure was the strongest factor with hyperuricemia. The association was the weakest in the Asian population. Waist circumference was the only significant factor associated with hyperuricemia in the Asian population. CONCLUSION: The prevalence of metabolic syndrome has an increasing pattern, but there was no specific decadal trend in prevalence of hyperuricemia. There is an ethnicity-specific association of metabolic syndrome and hyperuricemia, especially among Asians.

Genetic interactions reveal distinct biological and therapeutic implications in breast cancer.

Co-occurrence and mutual exclusivity of genomic alterations may reflect the existence of genetic interactions, potentially shaping distinct biological phenotypes and impacting therapeutic response in breast cancer. However, our understanding of them remains limited. Herein, we investigate a large-scale multi-omics cohort (n = 873) and a real-world clinical sequencing cohort (n = 4,405) including several clinical trials with detailed treatment outcomes and perform functional validation in patient-derived organoids, tumor fragments, and in vivo models. Through this comprehensive approach, we construct a network comprising co-alterations and mutually exclusive events and characterize their therapeutic potential and underlying biological basis. Notably, we identify associations between TP53mut-AURKAamp and endocrine therapy resistance, germline BRCA1mut-MYCamp and improved sensitivity to PARP inhibitors, and TP53mut-MYBamp and immunotherapy resistance. Furthermore, we reveal that precision treatment strategies informed by co-alterations hold promise to improve patient outcomes. Our study highlights the significance of genetic interactions in guiding genome-informed treatment decisions beyond single driver alterations.

Mobile monitoring system detects the disease activity pattern and shows the association with clinical outcomes in patients with newly diagnosed Crohn's disease.

We aimed to determine whether Crohn's disease (CD) activity patterns assessed via a web-based symptom diary can help predict clinical outcomes in patients with newly diagnosed CD. Patients diagnosed with CD within the preceding 3 months were prospectively enrolled at four tertiary centers. All patients recorded their symptoms on a website using a smartphone at least once a week. The index outcomes were disease-related admission and surgery during follow-up. The disease activity from enrollment to outcome or last follow-up was reviewed for pattern analysis. Cox regression analysis was used to identify the predictors of disease outcomes. A total of 102 patients were enrolled. During a median follow-up period of 42 months, 25 (24.5%) and 6 (5.9%) patients required admission and surgery, respectively. Poor activity pattern was an independent predictor of disease-related hospitalization (adjusted hazard ratio [aHR], 3.96; 95% confidence interval [CI] 1.5-10.45; p = 0.005). A poor activity pattern (aHR, 19.48; 95% CI 1.86-203.95; p = 0.013) and female sex (aHR, 11.28; 95% CI 1.49-85.01; p = 0.018) were found to be independent predictors of bowel resection. CD disease activity patterns monitored through the mobile monitoring system may help predict clinical outcomes, such as disease-related hospitalization and surgery, in patients with newly diagnosed CD.

Effects of glossopharyngeal nerve block on pain control after tonsillectomy: a systemic review and meta-analysis.

BACKGROUND: We investigated the role of perioperative intraoral glossopharyngeal nerve block to minimize postoperative pain in patients undergoing tonsillectomy through a meta-analysis of the relevant literature. METHODS: We retrieved eight studies from PubMed, Scopus, Embase, Web of Science, and Cochrane databases up to August 2023. We compared perioperative glossopharyngeal nerve block with a control group, in order to examine postoperative pain, analgesic use, and other postoperative morbidities. RESULTS: Postoperative pain was significantly reduced at 1-4 h (SMD -1.26, 95% CI [-2.35; -0.17], I2 = 94.7%, P = 0.02) and 5-8 hours (SMD -1.40, 95% CI [-2.47; -0.34], I2 = 96.1%, p = 0.01) in the treatment groups compared to the control group. However, glossopharyngeal nerve block showed no efficacy in reducing pain or use of analgesic drugs after 12 h compared to the control group. The incidences of postoperative bleeding (OR 0.95, 95% CI [0.35; 2.52], I2 = 0.0%), local agent toxicity (OR 4.14, 95% CI [0.44; 38.63], I2 = 0.0%), nasal problems (OR 1.25, 95% CI [0.60; 2.61], I2 = 0.0%), postoperative nausea and vomiting (OR 1.35, 95% CI [0.78; 2.33], I2 = 0.0%), swallowing difficulty (OR 1.61, 95% CI [0.76; 3.42], I2 = 56.0%), and voice change (OR 3.11, 95% CI [0.31; 30.80], I2 = 0.0%) were not significantly different between the treatment and control groups. The treatment group showed higher prevalence of respiratory problems and dry mouth compared to control without statistical significance, but a significant increase in throat discomfort (p = 0.02). CONCLUSION: Intraoral glossopharyngeal nerve block for tonsillectomy did not significantly impact postoperative pain management and was associated with some adverse effects with increases in respiratory problems, dry mouth, and throat discomfort compared to controls.

p53 inhibitor or antioxidants reduce the severity of ethmoid plate deformities in zebrafish Type 3 Treacher Collins syndrome model.

Treacher Collins syndrome-3 (TCS-3) is a rare congenital craniofacial disorder attributed to variants in the RNA pol I subunit C (POLR1C). The pathogenesis of TCS-3 linked to polr1c involves the activation of apoptosis-dependent p53 pathways within neural crest cells (NCCs). This occurs due to disruptions in ribosome biogenesis, and the restoration of polr1c expression in early embryogenesis effectively rescues the observed craniofacial phenotype in polr1c-deficient zebrafish. Clinical variability in TCS patients suggests interactions between genes and factors like oxidative stress. Elevated production of reactive oxygen species (ROS) in epithelial cells may worsen phenotypic outcomes in TCS individuals. Our study confirmed excessive ROS production in facial regions, inducing apoptosis and altering p53 pathways. Deregulated cell-cycle and epithelial-to-mesenchymal transition (EMT) genes were also detected in the TCS-3 model. Utilizing p53 inhibitor (Pifithrin-α; PFT-α) or antioxidants (Glutathione; GSH and N-Acetyl-L-cysteine; NAC) effectively corrected migrated NCC distribution in the pharyngeal arch (PA), suppressed oxidative stress, prevented cell death, and modulated EMT inducers. Crucially, inhibiting p53 activation or applying antioxidants within a specific time window, notably within 30 h post-fertilization (hpf), successfully reversed phenotypic effects induced by polr1c MO.

Unlocking synergies: Harnessing the potential of biological methane sequestration through metabolic coupling between Methylomicrobium alcaliphilum 20Z and Chlorella sp. HS2.

A halotolerant consortium between microalgae and methanotrophic bacteria could effectively remediate in situ CH4 and CO2, particularly using saline wastewater sources. Herein, Methylomicrobium alcaliphilum 20Z was demonstrated to form a mutualistic association with Chlorella sp. HS2 at a salinity level above 3.0%. Co-culture significantly enhanced the growth of both microbes, independent of initial inoculum ratios. Additionally, increased methane provision in enclosed serum bottles led to saturated methane removal. Subsequent analyses suggested nearly an order of magnitude increase in the amount of carbon sequestered in biomass in methane-fed co-cultures, conditions that also maintained a suitable cultural pH suitable for methanotrophic growth. Collectively, these results suggest a robust metabolic coupling between the two microbes and the influence of the factors other than gaseous exchange on the assembled consortium. Therefore, multi-faceted investigations are needed to harness the significant methane removal potential of the identified halotolerant consortium under conditions relevant to real-world operation scenarios.

Antimicrobial Resistance Profiles and Molecular Characteristics of Salmonella enterica Serovar Agona Isolated from Food-Producing Animals During 2010-2020 in South Korea.

Multidrug-resistant (MDR) Salmonella enterica serovar Agona infections affect public health globally. This investigation aimed to ascertain the antimicrobial resistance profiles and molecular characteristics of Salmonella Agona isolates obtained from food-producing animals. A total of 209 Salmonella Agona isolates were recovered from mostly chickens (139 isolates), pigs (56 isolates), cattle (11 isolates), and ducks (3 isolates) between 2010 and 2020 in South Korea. In addition, these Salmonella Agona isolates were obtained from 25 slaughterhouses nationwide. Furthermore, this serotype suddenly increased in chickens in 2020. Salmonella Agona from chickens showed high resistance (69-83%) to ampicillin, streptomycin, tetracycline, trimethoprim/sulfamethoxazole, and chloramphenicol. Moreover, chicken/duck isolates (83.1%) showed significantly higher levels of MDR than cattle/pig isolates (1.5%). For molecular analysis by pulsed-field gel electrophoresis, infrared spectroscopy biotyping, and multilocus sequence typing in combination, a total of 23 types were observed. Especially two major types, P1-III-2-13 and P1-IV-2-13, comprised 59.3% of the total isolates spreading in most farms. Moreover, Salmonella Agona sequence type (ST)13 was predominant (96.7%) among three different STs (ST13, ST11, and ST292) widely detected in chickens (94.3%) in most farms located nationwide. Taken together, MDR Salmonella Agona in chickens might pose a potential risk to public health through direct contact or the food chain.

Antiseptic Functions of CGK012 against HMGB1-Mediated Septic Responses.

High mobility group box 1 (HMGB1), a protein with important functions, has been recognized as a potential therapeutic target for the treatment of sepsis. One possible mechanism for this is that inhibiting HMGB1 secretion can exert antiseptic effects, which can restore the integrity of the vascular barrier. (7S)-(+)-cyclopentyl carbamic acid 8,8-dimethyl-2-oxo-6,7-dihydro-2H,8H-pyrano[3,2-g]chromen-7-yl-ester (CGK012) is a newly synthesized pyranocoumarin compound that could function as a novel small-molecule inhibitor of the Wnt/ß-catenin signaling pathway. However, no studies have yet determined the effects of CGK012 on sepsis. We investigated the potential of CGK012 to attenuate the excessive permeability induced by HMGB1 and enhance survival rates in a mouse model of sepsis with reduced HMGB1 levels following lipopolysaccharide (LPS) treatment. In both LPS-stimulated human endothelial cells and a mouse model exhibiting septic symptoms due to cecal ligation and puncture (CLP), we assessed proinflammatory protein levels and tissue damage biomarkers as indicators of reduced vascular permeability. CGK012 was applied after induction in human endothelial cells exposed to LPS and the CLP-induced mouse model of sepsis. CGK012 effectively mitigated excessive permeability and suppressed HMGB1 release, resulting in improved vascular stability, decreased mortality, and enhanced histological conditions in the mouse model of CLP-induced sepsis. In conclusion, our findings indicate that CGK012 treatment in mice with CLP-induced sepsis diminished HMGB1 release and increased the survival rate, suggesting its potential as a pharmaceutical intervention for sepsis.