Evaluating the Potential of Vegetable Powders as Nitrite Replacements in Cured Pork Sausages: Effects of Different Processing Methods to Produce Chinese Cabbage and Radish Powders.

This study investigated the potential of Chinese cabbage and radish powders as natural sources of nitrite in ground pork sausages. Four vegetable powders from Chinese cabbage and radish, depending on the processing method, were prepared for evaluation: filtered Chinese cabbage juice powder (FCJP), crushed Chinese cabbage powder (CCP), filtered radish juice powder (FRJP), and crushed radish powder (CRP). Both FCJP and FRJP from filtered juice of Chinese cabbages and radishes had higher total soluble solids and water soluble index compared to CCP and CRP from crushed Chinese cabbages and radishes. Additionally, FRJP and CRP showed a higher nitrate content than CCP and FCJP. The evaluation of vegetable powders against products containing sodium nitrite (control) or commercial vegetable powder in ground pork sausages showed that the use of FRJP and CRP resulted in similar levels of CIE a* compared to the control, whereas those cured with FCJP or CCP resulted in lower CIE a* values. However, regardless of the type and processing method of vegetables, all sausages treated with vegetable powders were similar in terms of cured pigment, total pigment, curing efficiency, and lipid oxidation compared with the control. Although lower hardness was observed in sausages treated with FRJP, no other treatments affected textural attributes. These results indicate that FRJP and CRP have great potential as natural curing agents for replacing nitrite in cured sausages. The use of powders obtained from filtered juices may provide extended utility as vegetable-based curing methods for other meat products.

Spin Hall-induced bilinear magnetoelectric resistance.

Magnetoresistance is a fundamental transport phenomenon that is essential for reading the magnetic states for various information storage, innovative computing and sensor devices. Recent studies have expanded the scope of magnetoresistances to the nonlinear regime, such as a bilinear magnetoelectric resistance (BMER), which is proportional to both electric field and magnetic field. Here we demonstrate that the BMER is a general phenomenon that arises even in three-dimensional systems without explicit momentum-space spin textures. Our theory suggests that the spin Hall effect enables the BMER provided that the magnitudes of spin accumulation at the top and bottom interfaces are not identical. The sign of the BMER follows the sign of the spin Hall effect of heavy metals, thereby evidencing that the BMER originates from the bulk spin Hall effect. Our observation suggests that the BMER serves as a general nonlinear transport characteristic in three-dimensional systems, especially playing a crucial role in antiferromagnetic spintronics.

Functional pathogenicity of ESRRB variant of uncertain significance contributes to hearing loss (DFNB35).

Advances in next-generation sequencing technologies have led to elucidation of sensorineural hearing loss genetics and associated clinical impacts. However, studies on the functional pathogenicity of variants of uncertain significance (VUS), despite their close association with clinical phenotypes, are lacking. Here we identified compound heterozygous variants in ESRRB transcription factor gene linked to DFNB35, specifically a novel splicing variant (NM_004452.4(ESRRB): c.397 + 2T>G) in trans with a missense variant (NM_004452.4(ESRRB): c.1144C>T p.(Arg382Cys)) whose pathogenicity remains unclear. The splicing variant (c.397 + 2T>G) caused exon 4 skipping, leading to premature stop codon formation and nonsense-mediated decay. The p.(Arg382Cys) variant was classified as a VUS due to its particularly higher allele frequency among East Asian population despite disease-causing in-silico predictions. However, functional assays showed that p.(Arg382Cys) variant disrupted key intramolecular interactions, leading to protein instability. This variant also reduced transcriptional activity and altered expression of downstream target genes essential for inner ear function, suggesting genetic contribution to disease phenotype. This study expanded the phenotypic and genotypic spectrum of ESRRB in DFNB35 and revealed molecular mechanisms underlying ESRRB-associated DFNB35. These findings suggest that variants with high allele frequencies can also possess functional pathogenicity, providing a breakthrough for cases where VUS, previously unexplored, could be reinterpreted by elucidating their functional roles and disease-causing characteristics.

Comparison of primary and secondary metabolites and antioxidant activities by solid-state fermentation of Apios americana Medikus with different fungi.

This study compared the nutritional components, isoflavones, and antioxidant activities by solid-sate fermentation of Apios americana Medikus (AAM) with seven different fungi. The total fatty acid contents increased from 120.5 mg/100 g (unfermented AAM, UFAAM) to 242.0 to 3167.5 mg/100 g (fermented AAM, FAAM) with all fungi. In particular, the values of total fatty acids were highest (26.3-fold increase) in the FAAM with Monascus purpureus. The amount of total free amino acids increased from 591.69 mg/100 g (UFAAM) to 664.38 to 1603.07 mg/100 g after fermentation except for Monascus pilosus and Lentinula edodes. The total mineral contents increased evidently after fermentation with M. purpureus, F. velutipes, and Tricholoma matsutake (347.36 â†’ 588.29, 576.59, and 453.32 mg/100 g, respectively). The UFAAM predominated isoflavone glycosides, whereas glycoside forms were converted into aglycone forms after fermentation by fungi. The bioconversion rates of glycoside to aglycone were excellent in the FAAM with M. pilosus, M. purpureus, F. velutipes, and T. matsutake (0.01 â†’ 0.69, 0.50, 0.27, and 0.31 mg/g, respectively). Furthermore, the total phenolic contents, total flavonoid contents, and antioxidant activities by the abovementioned FAAM were high except for L.edodes. This FAAM can be used as a potential food and pharmaceutical materials.

Comparisons of clinical outcomes between hypertensive and normotensive living kidney donors: a prospective, multicenter nationwide cohort study.

Background: Living kidney donors with hypertension are potential candidates for solving the donor shortages in renal transplantation. However, the safety of donors with hypertension after nephrectomy has not been sufficiently confirmed. Methods: A total of 642 hypertensive and 4,848 normotensive living kidney donors who were enrolled in the Korean Organ Transplantation Registry between May 2014 and December 2020 were included in this study. The study endpoints were a decreased estimated glomerular filtration rate (eGFR) and proteinuria. Results: In the entire cohort, donors with hypertension had a lower eGFR before nephrectomy in comparison to normotensive donors which remained lower after kidney transplantation. The incidence of proteinuria in hypertensive donors increased during follow-up. In propensity score-matched analysis, the risk of eGFR being <60 mL/min/1.73 m2 (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.50-1.19) or <45 mL/min/1.73 m2 (HR, 0.50; 95% CI, 0.06-4.03) was not significantly increased in donors with hypertension. However, hypertensive donors were found to have a significantly higher risk of proteinuria than normotensive donors (HR, 2.28; 95% CI, 1.05-4.94). Similar findings were also observed in the analysis of the entire cohort, indicating that hypertensive donors had a significantly higher risk of proteinuria (adjusted HR, 1.77; 95% CI, 1.10-2.85), without a substantial increase in the risk of decreased renal function. Conclusion: The risk of proteinuria after donation was substantially increased in donors with hypertension. These findings underscore the need for careful monitoring of proteinuria in hypertensive donors following donation.

Hospitalization among adults with chronic kidney disease: results from the KoreaN cohort study for Outcomes in patients With Chronic Kidney Disease (KNOW-CKD) study.

Background: Chronic kidney disease (CKD) patients are hospitalized for various conditions. Hospitalization increases the readmission rate and mortality rate, seriously deteriorating patients' quality of life. Consequently, it is crucial to analyze the reasons for hospitalization in CKD patients from a broader perspective according to CKD grade. Methods: This is a prospective cohort study of CKD patients entitled the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD). A total of 2,238 patients were examined, and the reasons for hospitalization were classified into 16 disease categories. The incidence rate ratio (IRR) according to CKD stage was compared using negative bimodal regression analysis. Results: The all-cause hospitalization incidence was 184.96 per 1,000 person-years. The most common reason for hospitalization was circulatory system disease, followed by infection and digestive system disease. Among hospitalizations for acute kidney injury, endocrine-nutrition-metabolic-related illness, blood-related disease, and diseases of the nervous system and sensory organs, IRR increased as CKD grade advanced. The incidence of ophthalmologic surgery during hospitalization increased according to the CKD stage. The IRR of KNOW-CKD patients was 6.19 (95% confidence interval, 5.92-6.48; p < 0.001) compared with the general population. Conclusion: This in-depth analysis of hospitalizations among CKD patients confirmed that CKD patients were hospitalized for various reasons, such as metabolic, ophthalmic, and hematologic diseases. Early detection and intervention regarding causative diseases of CKD are important to reduce the hospitalization burden and improve patients' quality of life.

Cardioprotective Effect of SGLT2 Inhibitor in Diabetic Kidney Transplant Recipients: A Multicenter Propensity Score Matched Study.

Introduction: Kidney transplantation (KT) improves the cardiovascular outcomes of patients with end-stage kidney disease. However, cardiovascular disease remains the leading cause of premature death and graft loss in KT recipients (KTRs) with diabetes. We evaluated the cardioprotective effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in KTRs with diabetes. Methods: A total of 750 KTRs with diabetes were enrolled from 6 tertiary hospitals. Among them, 129 patients (17.2%) were prescribed SGLT2i. The primary outcome was the incidence of major adverse cardiovascular events (MACE), which comprised myocardial infarction (MI), death from cardiovascular causes, hospitalization for heart failure, and stroke. Multivariable Cox regression analysis and propensity score matching were used to investigate the effect of SGLT2i on clinical outcomes. Results: In the matched cohort, MACE occurred in 5 patients (3.9%) in the SGLT2i group and 15 patients (11.8%) in the non-SGLT2i group, out of 127 patients in each group over 55.3 months. The incidence of MACE and MI was lower in the SGLT2i group than in the non-SGLT2i group (P = 0.036 and 0.008, respectively). In multivariate analysis, the SGLT2i group had a lower risk of MACE and MI than the non-SGLT2i group (adjusted hazard ratio [HR], 0.30 and 0.04; 95% confidence interval [CI], 0.10-0.88 and 0.004-0.40; P = 0.028 and 0.006, respectively). There was no difference in the incidence of urinary tract infection (UTI) between the 2 groups. Conclusion: SGLT2i significantly decreased the risk of cardiovascular events in KTRs with diabetes, particularly lowering the incidence of MI and death from cardiovascular causes. SGLT2i can be used to reduce the burden of cardiovascular disease in KTRs with diabetes.

Obstructive Sleep Apnea and Medical Comorbidities in the Asian Population: Evidence From a Nationwide Healthcare System Data in South Korea.

OBJECTIVE: Obstructive sleep apnea (OSA) is a breathing disorder characterized by recurrent airway obstruction during sleep. Previous western studies have investigated the link between medical disorders and the pathophysiology of OSA. The prevalence and comorbidity rates of OSA; however, vary across different countries and racial groups. This study aimed to delve into medical comorbidities in patients with OSA using a large nationwide healthcare database in Korea. METHODS: This nationwide study used the Korean National Health Insurance claims database (2010-2019). The effect of OSA on the incidence of medical disorders was estimated using the Cox proportional hazard ratio (HR) model. The results were reported as crude and adjusted HRs with 95% confidence intervals (CI). Subgroup analysis was conducted by sex and age. RESULTS: In total, 103,785 patients with OSA and 207,570 patients without OSA were included. OSA group had significantly higher HRs for ischemic heart disease and stroke even after adjusting for hypertension, dyslipidemia, and diabetes. The OSA group also showed an increased risk of metabolic syndrome-related diseases, chronic kidney disease, and gastroesophageal reflux disease. Female patients with OSA exhibited notably higher rates of comorbid liver cirrhosis, chronic obstructive pulmonary disease, and asthma. The cardiovascular burden of patients increased in accordance with the patients' age. CONCLUSION: Korean patients with OSA have a significantly increased risk of cardio-cerebrovascular diseases, which aligns with the previous studies conducted in the western countries. This result holds particular significance as it represents the first nationwide, population-based study conducted in Asia.

Impact of Arterial Calcification on Cardiovascular and Renal Outcomes in Kidney Transplant Patients.

Introduction: Coronary artery calcification score (CACS) and abdominal aortic calcification score (AACS) are both well-established markers of vascular stiffness, and previous studies have shown that a higher CACS is a risk factor for chronic kidney disease (CKD) progression. However, the impact of pretransplant CACS and AACS on cardiovascular and renal outcomes in kidney transplant patients has not been established. Methods: We included 944 kidney transplant recipients from the KoreaN cohort study for Outcome in patients With Kidney Transplantation (KNOW-KT) cohort and categorized them into three groups (low, medium, and high) according to baseline CACS (0, 0 < and ≤100, >100) and AACS (0, 1-4, >4). The low (0), medium (0 < and ≤ 100), and high (>100) CACS groups each consisted of 462, 213, and 225 patients, respectively. Similarly, the low (0), medium (1-4), and high (>4) AACS groups included 638, 159, and 147 patients, respectively. The primary outcome was the occurrence of cardiovascular events. The secondary outcomes were all-cause mortality and composite kidney outcomes, which comprised of >50% decline in the estimated glomerular filtration rate and graft loss. Cox regression analysis was used to investigate the association between baseline CACS/AACS and outcomes. Results: The high CACS group (N = 462) faced a significantly higher risk for cardiovascular outcomes (adjusted hazard ratio [aHR], 5.97; 95% confidence interval [CI], 2.01-17.7) and all-cause mortality (aHR, 2.74; 95% CI, 1.27-5.92) compared to the low CACS group (N = 225). Similarly, the high AACS group (N = 638) had an elevated risk for cardiovascular outcomes (aHR, 2.38; 95% CI, 1.16-4.88). Furthermore, the addition of CACS to prediction models improved prediction indices for cardiovascular outcomes. However, the risk of renal outcomes did not differ among CACS or AACS groups. Conclusion: Pretransplant arterial calcification, characterized by high CACS or AACS, is an independent risk factor for cardiovascular outcomes and mortality in kidney transplant patients.

Arterial calcification, accumulation of calcium in the arterial walls, vascular stiffness, and loss of elasticity of blood vessels can contribute to the development of cardiovascular diseases. Patients with chronic kidney disease and those undergoing dialysis have a considerably increased risk of vascular calcification. Even after kidney transplantation when kidney function has been restored, the prevalence of vascular calcification and subsequent cardiovascular disease remains high. Coronary artery calcification score and abdominal aortic calcification score are both well-established markers of vascular calcification. However, the impact of pretransplant vascular calcification scores on cardiovascular and renal outcomes in kidney transplant patients has not been established. When we analyzed 944 Korean kidney transplant patients, both vascular calcification scores were significantly associated with cardiovascular outcomes after kidney transplantation, but were not associated with renal outcomes. We also demonstrated that the addition of coronary artery calcification scores led to a modest improvement in the prediction performance for kidney transplant outcomes. Our findings suggest a potential role of pretransplant screening of coronary calcification scores and aortic calcification scores in risk stratification for post-kidney transplant outcomes.

Minimally Invasive Open Bilateral Total Thyroidectomy Using Unilateral Neck Incision in Thyroid Cancer: Preliminary Surgical and Quality of Life Outcomes.

PURPOSE: Thyroid cancer incidence has increased in recent decades, and thyroid surgery is continuously evolving in response to demands for postoperative comfort and cosmesis. This study aimed to introduce a new surgical method for minimally invasive open bilateral total thyroidectomy (MI-BTT) using a unilateral 2.5-3.0 cm neck incision. Furthermore, we reported the surgical outcomes and postoperative quality of life (QoL) using a validated Korean translated Dermatology Life Quality Index (DLQI) questionnaire. MATERIALS AND METHODS: We retrospectively evaluated 41 Asian patients who underwent MI-BTT for low-risk papillary thyroid cancer by a single surgeon from March 2019 to December 2021. RESULTS: A total of 4 male and 37 female patients were included. The mean age and body mass index were 46.2±10.1 years and 23.3±3.3 kg/m², respectively. The average tumor size was 1.1±0.6 cm, and 36 patients (87.8%) had bilateral cancer. Twenty-three (56.1%) patients had occult central lymph node (CLN) metastasis in the final pathologic report, with the mean number of dissected CLNs being 7.2±6.5. Gross capsular extension was found in 6 patients (14.6%). Moreover, 28 patients (68.3%) received additional treatment after surgery with low or high doses of radioactive iodine. The average serum-stimulated thyroglobulin value identified during treatment was 1.57±2.30 ng/mL. The mean operation time was 78.0±13.9 minutes, and postoperative complications included transient hypocalcemia (36.6%), transient hoarseness (24.4%), and seroma (2.4%). The mean total DLQI score was 2.73±0.78, indicating a small effect on QoL. CONCLUSION: MI-BTT is a novel, safe, and feasible technique to improve patient satisfaction for surgical scars and QoL.

Differences in Electroencephalography Power and Asymmetry at Frontal Region in Young Adults with Attention-deficit/hyperactivity Disorder: A Quantitative Electroencephalography Study.

Objective: : Diagnosing attention-deficit/hyperactivity disorder (ADHD) in adults is often hard. This study aimed to determine differences in absolute EEG power and frontal asymmetry between individuals with ADHD and non-ADHD in young adults aged 18-30 years. Methods: : Young adult (age: 18-30 years) outpatients (n = 103) including ADHD patients (n = 51) and non-ADHD patients (n = 52) were enrolled. QEEG was performed for both groups for each region of the brain. The absolute power of each frequency measured in three frontal regions (Lt., Mid., Rt.) of the scalp area was compared between the two groups. Differences between the two groups including theta/beta ratio were compared. Frontal asymmetries were also evaluated for prefrontal (Fp2-Fp1), middle frontal (F4-F3), lateral frontal (F8-F7) pairs at all frequencies. Correlation analysis was performed for absolute powers, frontal asymmetry, and Stroop tests. Results: : Demographic data, neuropsychological tests, and psychiatric symptoms were not significantly different between the two groups. Delta band was significantly increased while beta band was decreased in the middle frontal area of the ADHD group as compared with those of the non-ADHD group. For frontal asymmetries, all frequencies in the middle frontal area were more rightward in ADHD patients than in non-ADHD patients. Absolute powers in delta, beta band, and frontal asymmetry in all frequencies had correlations with Stroop tests. Conclusion: : This study revealed that ADHD patients had significant differences in absolute powers in delta, beta bands, and frontal asymmetries in all frequencies. Our findings suggest that QEEG can be a helpful tool for diagnosing ADHD in psychiatric patients.

Relationship between recurrence and age in the diffuse sclerosing variant of papillary thyroid carcinoma: clinical significance in pediatric patients.

Background: The diffuse sclerosing variant (DSV) is among the aggressive variants of papillary thyroid carcinoma (PTC) and is more prevalent in pediatric patients than in adult patients. Few studies have assessed its characteristics owing to its low incidence. We aimed to evaluate the relationship between recurrence and age in the DSV of PTC. Methods: We retrospectively reviewed patients diagnosed with the DSV or conventional PTC (cPTC) after surgery at a medical center between May 1988 and January 2019. We compared the clinico-pathological characteristics and surgical outcomes of the DSV and cPTC groups and between adult and pediatric patients with DSV. Results: Among the 24,626 patients, 202 had the DSV, and 24,424 were diagnosed with cPTC. The recurrence rate was significantly higher in the DSV group than in the cPTC group. In the DSV group, the recurrence rate was significantly higher in the pediatric patient group than in the adult patient group. Moreover, the association between recurrence and age group showed different patterns between the DSV and cPTC groups with restricted cubic splines (RCS). While both RCS curves showed a U-shaped distribution, the RCS curve tended to be located within the younger age group. Conclusions: This study demonstrated that pediatric patients with DSV are at a greater risk for recurrence compared with adult patients; moreover, the pattern of recurrence risk according to age is different from that of cPTC.

Association between age-adjusted Endothelial Activation and Stress Index and ICU mortality in patients with severe coronavirus disease-2019.

BACKGROUND: Endothelial Activation and Stress Index (EASIX) reflects endothelial dysfunction or damage. Because endothelial dysfunction is one of the key mechanisms, a few studies have shown the clinical usefulness of original and age-adjusted EASIX (age-EASIX) in patients with coronavirus disease-19 (COVID-19). We aimed to evaluate the clinical utility of age-EASIX in predicting ICU mortality in critically ill patients with COVID-19 in South Korea. METHODS: Secondary analysis was performed using clinical data retrospectively collected from 22 nationwide hospitals in South Korea between January 1, 2020, and August 31, 2021. Patients were at least 19 years old and admitted to the ICU for severe COVID-19, demanding at least high-flow nasal cannula oxygen therapy. EASIX [lactate dehydrogenase (U/L) × creatinine (mg/dl) /platelet count (109 cells/L)] and age-EASIX (EASIX × age) were calculated and log2-transformed. RESULTS: The mean age of 908 critically ill patients with COVID-19 was 67.4 years with 59.7% male sex. The mean log2 age-EASIX was 7.38 ± 1.45. Non-survivors (n=222, 24.4%) in the ICU had a significantly higher log2 age-EASIX than of survivors (8.2 ± 1.52 vs 7.1 ± 1.32, P<0.001). Log2 age-EASIX was significantly associated with ICU mortality (odds ratio, 1.541; 95% confidence interval, 1.322-1.796, P<0.001) and had a better area under the receiver operating characteristic curve than of the sequential organ failure assessment (SOFA) score in predicting ICU mortality (0.730 vs 0.660, P=0.001). CONCLUSION: Age-EASIX is significantly associated with ICU mortality and has better discriminatory ability than the SOFA score in predicting ICU mortality.

The Potential Substitution of Oyster Shell Powder for Phosphate in Pork Patties Cured with Chinese Cabbage and Radish Powder.

The use of natural ingredients in meat processing has recently gained considerable interest, as consumers are increasingly attracted to clean-label meat products. However, limited research has been conducted on the use of natural substitutes for synthetic phosphates in the production of clean-label meat products. Therefore, this study aimed to explore the potential of oyster shell powder as a substitute for synthetic phosphates in pork patties cured with Chinese cabbage or radish powders. Four different groups of patties were prepared using a combination of 0.3% or 0.6% oyster shell powder and 0.4% Chinese cabbage or radish powder, respectively. These were compared with a positive control group that contained added nitrite, phosphate, and ascorbate and a negative control group without these synthetic ingredients. The results showed that patties treated with oyster shell powder had lower (p<0.05) cooking loss, thickness and diameter shrinkage, and lipid oxidation than the negative control but had lower (p<0.05) residual nitrite content and curing efficiency than the positive control. However, the use of 0.6% oyster shell powder adversely affected the curing process, resulting in a decreased curing efficiency. The impact of the vegetable powder types tested in this study on the quality attributes of the cured pork patties was negligible. Consequently, this study suggests that 0.3% oyster shell powder could serve as a suitable replacement for synthetic phosphate in pork patties cured with Chinese cabbage or radish powders. Further research on the microbiological safety and sensory evaluation of clean-label patties during storage is required for practical applications.

CX3CR1+ macrophages interact with hepatic stellate cells to promote hepatocellular carcinoma through CD8+ T cell suppression.

BACKGROUND AND AIMS: Hepatic stellate cells (HSCs) contribute to hepatocellular carcinoma (HCC) progression by regulating multiple factors. However, the entire immunoregulatory functions of HSCs are still obscure. Here, we aim to investigate whether HSCs impose CX3CR1+ macrophages to pro-tumorigenic properties in the peritumoral area. APPROACH AND RESULTS: In single cell RNA-sequencing analysis of HCC patients, a subpopulation of macrophages specifically expressed Arg1 and Cx3cr1 in the peritumoral area, and were highly enriched with retinol metabolism-related genes. Flow cytometry analysis showed significantly increased frequencies of CD14+CD11b+HLA-DR‒ macrophages with CX3CR1 in the HCC adjacent region where α-SMA-expressing activated HSCs (aHSCs) showed co-localized expression of CX3CL1. Accordingly, in tumor-bearing mice, Cx3cl1 mRNA expression was notably increased in aHSCs within the adjacent HCC, where infiltration of CX3CR1+Ly6C+ macrophages was mostly observed with decreased CD8+ T cells. In adoptive transfer and in vitro co-culture of myeloid cells, we demonstrated that CX3CR1+Ly6C+ macrophages migrated and highly expressed arginase-1 by interacting with retinoid-enriched aHSCs in the adjacent HCC. Direct treatment of retinoids or co-culturing with retinol-storing mouse aHSCs or human LX-2 cells significantly increased arginase-1 expression in CX3CR1+Ly6C+ macrophages and human blood CD14+ cells, leading to the suppression of CD8+ T cell proliferation. Moreover, genetic deficiency of CX3CR1 in myeloid cells or pharmacological inhibition of retinol metabolism remarkably attenuated HCC development. CONCLUSION: We showed that CX3CR1+Ly6C+ macrophages migrate and interact with aHSCs in the peritumoral region where retinoids induce arginase-1 expression in CX3CR1+Ly6C+ macrophages, subsequently depriving CD8+ T cells of arginine and promoting HCC.

Chemical Compositions before and after Lactic Acid Fermentation of Isoflavone-Enriched Soybean Leaves and Their Anti-Obesity and Gut Microbiota Distribution Effects.

In this study, we prepared fermented products of isoflavone-enriched soybean leaves (IESLs) and analyzed their nutrients, isoflavones, anti-obesity efficacy, and effects on gut microbiota. Fermented IESLs (FIESLs) were found to be rich in nutrients, especially lauric acid, oleic acid, and linoleic acid. In addition, the concentrations of most essential free amino acids were increased compared to those of IESLs. The contents of bioactive compounds, such as total phenolic, total flavonoid, daidzein, and genistein, significantly increased as well. In addition, FIESLs administration in a high-fat diet (HFD) animal model improved the final body weight, epididymal fat, total lipid, triglyceride, total cholesterol, blood glucose, and leptin levels, as well as reverting microbiota dysbiosis. In conclusion, these findings indicate that FIESLs have the potential to inhibit obesity caused by HFDs and serve as a modulator of gut microbiota, offering the prevention of diet-induced gut dysbiosis and metabolite diseases associated with obesity.

Feasibility study for the development of multilayered solar cells for proton linear energy transfer depth profile measurement.

BACKGROUND: Previous study proposed a method to measure linear energy transfer (LET) at specific points using the quenching magnitude of thin film solar cells. This study was conducted to propose a more advanced method for measuring the LET distribution. PURPOSE: This study focuses on evaluating the feasibility of estimating the proton LET distribution in proton therapy. The feasibility of measuring the proton LET and dose distribution simultaneously using a single-channel configuration comprising two solar cells with distinct quenching constants is investigated with the objective of paving the way for enhanced proton therapy dosimetry. METHODS: Two solar cells with different quenching constants were used to estimate the proton LET distribution. Detector characteristics (e.g., dose linearity and dose-rate dependency) of the solar cells were evaluated to assess their suitability for dosimetry applications. First, using a reference beam condition, the quenching constants of the two solar cells were determined according to the modified Birks equation. The signal ratios of the two solar cells were then evaluated according to proton LET in relation to the estimated quenching constants. The proton LET distributions of six test beams were obtained by measuring the signal ratios of the two solar cells at each depth, and the ratios were evaluated by comparing them with those calculated by Monte Carlo simulation. RESULTS: The detector characterization of the two solar cells including dose linearity and dose-rate dependence affirmed their suitability for use in dosimetry applications. The maximum difference between the LET measured using the two solar cells and that calculated by Monte Carlo simulation was 2.34 keV/µm. In the case of the dose distribution measured using the method proposed in this study, the maximum difference between range measured using the proposed method and that measured using a multilayered ionization chamber was 0.7 mm. The expected accuracy of simultaneous LET and dose distribution measurement using the method proposed in this study were estimated to be 3.82%. The signal ratios of the two solar cells, which are related to quenching constants, demonstrated the feasibility of measuring LET and dose distribution simultaneously. CONCLUSION: The feasibility of measuring proton LET and dose distribution simultaneously using two solar cells with different quenching constants was demonstrated. Although the method proposed in this study was evaluated using a single channel by varying the measuring depth, the results suggest that the proton LET and dose distribution can be simultaneously measured if the detector is configured in a multichannel form. We believe that the results presented in this study provide the envisioned transition to a multichannel configuration, with the promise of substantially advancing proton therapy's accuracy and efficacy in cancer treatment.

Novel IL-4/HB-EGF-dependent crosstalk between eosinophils and macrophages controls liver regeneration after ischaemia and reperfusion injury.

OBJECTIVE: Previous studies indicate that eosinophils are recruited into the allograft following orthotopic liver transplantation and protect from ischaemia reperfusion (IR) injury. In the current studies, we aim to explore whether their protective function could outlast during liver repair. DESIGN: Eosinophil-deficient mice and adoptive transfer of bone marrow-derived eosinophils (bmEos) were employed to investigate the effects of eosinophils on tissue repair and regeneration after hepatic IR injury. Aside from exogenous cytokine or neutralising antibody treatments, mechanistic studies made use of a panel of mouse models of eosinophil-specific IL-4/IL-13-deletion, cell-specific IL-4rα-deletion in liver macrophages and hepatocytes and macrophage-specific deletion of heparin-binding epidermal growth factor-like growth factor (hb-egf). RESULT: We observed that eosinophils persisted over a week following hepatic IR injury. Their peak accumulation coincided with that of hepatocyte proliferation. Functional studies showed that eosinophil deficiency was associated with a dramatic delay in liver repair, which was normalised by the adoptive transfer of bmEos. Mechanistic studies demonstrated that eosinophil-derived IL-4, but not IL-13, was critically involved in the reparative function of these cells. The data further revealed a selective role of macrophage-dependent IL-4 signalling in liver regeneration. Eosinophil-derived IL-4 stimulated macrophages to produce HB-EGF. Moreover, macrophage-specific hb-egf deletion impaired hepatocyte regeneration after IR injury. CONCLUSION: Together, these studies uncovered an indispensable role of eosinophils in liver repair after acute injury and identified a novel crosstalk between eosinophils and macrophages through the IL-4/HB-EGF axis.

Inhibition of ribonucleotide reductase subunit M2 enhances the radiosensitivity of metastatic pancreatic neuroendocrine tumor.

Ribonucleotide Reductase (RNR) is a rate-limiting enzyme in the production of deoxyribonucleoside triphosphates (dNTPs), which are essential substrates for DNA repair after radiation damage. We explored the radiosensitization property of RNR and investigated a selective RRM2 inhibitor, 3-AP, as a radiosensitizer in the treatment of metastatic pNETs. We investigated the role of RNR subunit, RRM2, in pancreatic neuroendocrine (pNET) cells and responses to radiation in vitro. We also evaluated the selective RRM2 subunit inhibitor, 3-AP, as a radiosensitizer to treat pNET metastases in vivo. Knockdown of RNR subunits demonstrated that RRM1 and RRM2 subunits, but not p53R3, play significant roles in cell proliferation. RRM2 inhibition activated DDR pathways through phosphorylation of ATM and DNA-PK protein kinases but not ATR. RRM2 inhibition also induced Chk1 and Chk2 phosphorylation, resulting in G1/S phase cell cycle arrest. RRM2 inhibition sensitized pNET cells to radiotherapy and induced apoptosis in vitro. In vivo, we utilized pNET subcutaneous and lung metastasis models to examine the rationale for RNR-targeted therapy and 3-AP as a radiosensitizer in treating pNETs. Combination treatment significantly increased apoptosis of BON (human pNET) xenografts and significantly reduced the burden of lung metastases. Together, our results demonstrate that selective RRM2 inhibition induced radiosensitivity of metastatic pNETs both in vitro and in vivo. Therefore, treatment with the selective RRM2 inhibitor, 3-AP, is a promising radiosensitizer in the therapeutic armamentarium for metastatic pNETs.

Association between progression of coronary artery calcification and development of kidney failure with replacement therapy: Findings from KNOW-CKD study.

BACKGROUND AND AIMS: High coronary artery calcification (CAC) burden is a significant risk factor for adverse cardiovascular and kidney outcomes. However, it is unknown whether changes in the coronary atherosclerotic burden can accompany changes in kidney disease progression. Here, we evaluated the relationship between CAC progression and the risk of kidney failure with replacement therapy (KFRT). METHODS: We analyzed 1173 participants with chronic kidney disease (CKD) G1 to G5 without kidney replacement therapy from the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD). Participants were categorized into three groups according to the change in the CAC score between enrollment and year 4 (non-progressors, ≤0 AU; moderate progressors, 1-199 AU; and severe progressors, ≥200 AU). The primary outcome was the development of KFRT. RESULTS: During a follow-up period of 4690 person-years (median, 4.2 years), the primary outcome occurred in 230 (19.6 %) participants. The incidence of KFRT was 37.6, 54.3, and 80.9 per 1000 person-years in the non-, moderate, and severe progressors, respectively. In the multivariable cause-specific hazard model, the hazard ratios (HRs) for the moderate and severe progressors were 1.71 (95 % confidence interval [CI], 1.02-2.87) and 2.55 (95 % CI, 1.07-6.06), respectively, compared with non-progressors. A different definition of CAC progression with a threshold of 100 AU yielded similar results in a sensitivity analysis. CONCLUSIONS: CAC progression is associated with an increased risk of KFRT in patients with CKD. Our findings suggest that coronary atherosclerosis changes increase the risk of CKD progression.