Integrative transcriptomic and genomic analyses unveil the IFI16 variants and expression as MASLD progression markers.

BACKGROUND AND AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses a broad and continuous spectrum of liver diseases ranging from fatty liver to steatohepatitis. The intricate interactions of genetic, epigenetic, and environmental factors in the development and progression of MASLD remain elusive. Here, we aimed to achieve an integrative understanding of the genomic and transcriptomic alterations throughout the progression of MASLD. APPROACH AND RESULTS: RNA-Seq profiling (n = 146) and whole-exome sequencing (n = 132) of MASLD liver tissue samples identified 3 transcriptomic subtypes (G1-G3) of MASLD, which were characterized by stepwise pathological and molecular progression of the disease. Macrophage-driven inflammatory activities were identified as a key feature for differentiating these subtypes. This subtype-discriminating macrophage interplay was significantly associated with both the expression and genetic variation of the dsDNA sensor IFI16 (rs6940, A>T, T779S), establishing it as a fundamental molecular factor in MASLD progression. The in vitro dsDNA-IFI16 binding experiments and structural modeling revealed that the IFI16 variant exhibited increased stability and stronger dsDNA binding affinity compared to the wild-type. Further downstream investigation suggested that the IFI16 variant exacerbated DNA sensing-mediated inflammatory signals through mitochondrial dysfunction-related signaling of the IFI16-PYCARD-CASP1 pathway. CONCLUSIONS: This study unveils a comprehensive understanding of MASLD progression through transcriptomic classification, highlighting the crucial roles of IFI16 variants. Targeting the IFI16-PYCARD-CASP1 pathway may pave the way for the development of novel diagnostics and therapeutics for MASLD.

Role of the CCL20/CCR6 axis in tubular epithelial cell injury: Kidney-specific translational insights from acute kidney injury to chronic kidney disease.

This study investigated the role of the axis involving chemokine receptor 6 (CCR6) and its ligand chemokine (C-C motif) ligand 20 (CCL20) in acute kidney disease (AKD) using an ischemia-reperfusion injury (IRI) model. The model was established by clamping the unilateral renal artery pedicle of C57BL/6 mice for 30 min, followed by evaluation of CCL20/CCR6 expression at 4 weeks post-IRI. In vitro studies were conducted to examine the effects of hypoxia and H2 O2 -induced oxidative stress on CCL20/CCR6 expression in kidney tissues of patients with AKD and chronic kidney disease (CKD). Tubular epithelial cell apoptosis was more severe in C57BL/6 mice than in CCL20 antibody-treated mice, and CCR6, NGAL mRNA, and IL-8 levels were higher under hypoxic conditions. CCL20 blockade ameliorated apoptotic damage in a dose-dependent manner under hypoxia and reactive oxygen species injury. CCR6 expression in IRI mice indicated that the disease severity was similar to that in patients with the AKD phenotype. Morphometry of CCL20/CCR6 expression revealed a higher likelihood of CCR6+ cell presence in CKD stage 3 patients than in stage 1-2 patients. Kidney tissues of patients with CKD frequently contained CCL20+ cells, which were positively correlated with interstitial inflammation. CCL20/CCR6 levels were increased in fibrotic kidneys at 4 and 8 weeks after 5/6 nephrectomy. These findings suggest that modulating the CCL20/CCR6 pathway is a potential therapeutic strategy for managing the progression of AKD to CKD.

Anti-Inflammatory Response of New Postbiotics in TNF-α/IFN-γ-Induced Atopic Dermatitis-like HaCaT Keratinocytes.

This study examines the synergistic interaction between the immunomodulatory functions of lactic acid bacteria postbiotics and the anti-inflammatory properties of Smilax china L. extract through a combined fermentation process. Using atopic dermatitis (AD) as a model, characterized by an immune imbalance that leads to skin inflammation, we developed a fermented product, MB-2006, and compared its effects to those of the heat-killed probiotics Lactobacillus acidophilus (LAC) and Lactobacillus rhamnosus (LRH). Our experiments focused on elucidating the mechanism of action of MB-2006 in AD-like HaCaT keratinocyte cells, particularly its impact on the NF-κB pathway, a pivotal regulator of inflammation. MB-2006 proved more effective in reducing inflammation markers, such as IL-4 and thymic stromal lymphopoietin (TSLP), and in inhibiting NF-κB activation compared to LAC and LRH. Significantly, MB-2006 also reduced the expression of thymus- and activation-regulated chemokine (TARC), highlighting a synergistic effect that enhances its therapeutic potential. These results suggest that the combined fermentation of Smilax china L. extract with lactic acid bacteria enhanced both the anti-inflammatory and immunomodulatory effects, presenting a promising integrative approach to treating conditions like AD. Further studies are needed to validate these results in clinical settings and fully explore the potential of this synergistic fermentation process.

Inflammatory chemokine (C-C motif) ligand 8 inhibition ameliorates peritoneal fibrosis.

Peritoneal fibrosis (PF) is an irreversible complication of peritoneal dialysis (PD) that leads to loss of peritoneal membrane function. We investigated PD effluent and serum levels and the tissue expression of chemokine (C-C motif) ligand 8 (CCL8) in patients with PD. Additionally, we investigated their association with PF in a mouse model. Eighty-two end-stage renal disease (ESRD) patients with PD were examined. CCL8 levels were measured via enzyme-linked immunosorbent assays in PD effluents and serum and analyzed with peritoneal transport parameters. Human peritoneal mesothelial cells (hPMCs) were obtained from the PD effluents of 20 patients. Primary cultured hPMCs were treated with recombinant (r) transforming growth factor (TGF)-ß, and CCL8 expression was assessed via western blotting. As the duration of PD increased, the concentration of CCL8 in PD effluents significantly increased. Correlations between peritoneal transport parameters and dialysate CCL8 levels were observed. Western blotting analysis showed that CCL8 was upregulated via rTGF-ß treatment, accompanied by increases in markers of inflammation, fibrosis, senescence, and apoptosis in hPMCs after induction of fibrosis with rTGF-ß. Anti-CCL8 monoclonal antibody (mAb) treatment suppressed the rTGF-ß-induced increase in all analyzed markers. Immunohistochemical analysis revealed that CCL8 along with fibrosis- and inflammation-related markers were significantly increased in the PF mouse model. Functional blockade of CCL8 using a CCR8 inhibitor (R243) abrogated peritoneal inflammation and fibrosis in vivo. In conclusion, high CCL8 levels in PD effluents may be associated with an increased risk of PD failure, and the CCL8 pathway is associated with PF. CCL8 blockade can ameliorate peritoneal inflammation and fibrosis.

Cutting Edge: Bispecific γδ T Cell Engager Containing Heterodimeric BTN2A1 and BTN3A1 Promotes Targeted Activation of Vγ9Vδ2+ T Cells in the Presence of Costimulation by CD28 or NKG2D.

Vγ9Vδ2+ T cell-targeted immunotherapy is of interest to harness its MHC-independent cytotoxic potential against a variety of cancers. Recent studies have identified heterodimeric butyrophilin (BTN) 2A1 and BTN3A1 as the molecular entity providing "signal 1" to the Vγ9Vδ2 TCR, but "signal 2" costimulatory requirements remain unclear. Using a tumor cell-free assay, we demonstrated that a BTN2A1/3A1 heterodimeric fusion protein activated human Vγ9Vδ2+ T cells, but only in the presence of costimulatory signal via CD28 or NK group 2 member D. Nonetheless, addition of a bispecific γδ T cell engager BTN2A1/3A1-Fc-CD19scFv alone enhanced granzyme B-mediated killing of human CD19+ lymphoma cells when cocultured with Vγ9Vδ2+ T cells, suggesting expression of costimulatory ligand(s) on tumor cells is sufficient to satisfy the "signal 2" requirement. These results highlight the parallels of signal 1 and signal 2 requirements in αß and γδ T cell activation and demonstrate the utility of heterodimeric BTNs to promote targeted activation of γδ T cells.

LIGHT (TNFSF14) Costimulation Enhances Myeloid Cell Activation and Antitumor Immunity in the Setting of PD-1/PD-L1 and TIGIT Checkpoint Blockade.

Coinhibition of TIGIT (T cell immunoreceptor with Ig and ITIM domains) and PD-1/PD-L1 (PD-1/L1) may improve response rates compared with monotherapy PD-1/L1 blockade in checkpoint naive non-small cell lung cancer with PD-L1 expression >50%. TIGIT mAbs with an effector-competent Fc can induce myeloid cell activation, and some have demonstrated effector T cell depletion, which carries a clinical liability of unknown significance. TIGIT Ab blockade translates to antitumor activity by enabling PVR signaling through CD226 (DNAM-1), which can be directly inhibited by PD-1. Furthermore, DNAM-1 is downregulated on tumor-infiltrating lymphocytes (TILs) in advanced and checkpoint inhibition-resistant cancers. Therefore, broadening clinical responses from TIGIT blockade into PD-L1low or checkpoint inhibition-resistant tumors, may be induced by immune costimulation that operates independently from PD-1/L1 inhibition. TNFSF14 (LIGHT) was identified through genomic screens, in vitro functional analysis, and immune profiling of TILs as a TNF ligand that could provide broad immune activation. Accordingly, murine and human bifunctional fusion proteins were engineered linking the extracellular domain of TIGIT to the extracellular domain of LIGHT, yielding TIGIT-Fc-LIGHT. TIGIT competitively inhibited binding to all PVR ligands. LIGHT directly activated myeloid cells through interactions with LTßR (lymphotoxin ß receptor), without the requirement for a competent Fc domain to engage Fcγ receptors. LIGHT costimulated CD8+ T and NK cells through HVEM (herpes virus entry mediator A). Importantly, HVEM was more widely expressed than DNAM-1 on T memory stem cells and TILs across a range of tumor types. Taken together, the mechanisms of TIGIT-Fc-LIGHT promoted strong antitumor activity in preclinical tumor models of primary and acquired resistance to PD-1 blockade, suggesting that immune costimulation mediated by LIGHT may broaden the clinical utility of TIGIT blockade.

Production of light olefins and monocyclic aromatic hydrocarbons from the pyrolysis of waste plastic straws over high-silica zeolite-based catalysts.

Owing to the ever-increasing generation of plastic waste, the need to develop environmentally friendly disposal methods has increased. This study explored the potential of waste plastic straw to generate valuable light olefins and monocyclic aromatic hydrocarbons (MAHs) via catalytic pyrolysis using high-silica zeolite-based catalysts. HZSM-5 (SiO2/Al2O3:200) exhibited superior performance, yielding more light olefins (49.8 wt%) and a higher MAH content than Hbeta (300). This was attributed to the increased acidity and proper shape selectivity. HZSM-5 displayed better coking resistance (0.7 wt%) than Hbeta (4.4 wt%) by impeding secondary reactions, limiting coke precursor formation. The use of HZSM-5 (80) resulted in higher MAHs and lower light olefins than HZSM-5 (200) because of its higher acidity. Incorporation of Co into HZSM-5 (200) marginally lowered light olefin yield (to 44.0 wt%) while notably enhancing MAH production and boosting propene selectivity within the olefin composition. These observations are attributed to the well-balanced coexistence of Lewis and Brønsted acid sites, which stimulated the carbonium ion mechanism and induced H-transfer, cyclization, Diels-alder, and dehydrogenation reactions. The catalytic pyrolysis of plastic straw over high-silica and metal-loaded HZSM-5 catalysts has been suggested as an efficient and sustainable method for transforming plastic waste materials into valuable light olefins and MAHs.

The prognostic value of the phosphate-to-albumin ratio in patients with OHCA: A multicenter observational study.

PURPOSE: In patients with out-of-hospital cardiac arrest (OHCA), early and accurate outcome prediction is crucial for making treatment decisions and informing their relatives. A previous study reported an association between high phosphate levels and unfavorable neurological outcomes after return of spontaneous circulation (ROSC); however, its prognostic value was insufficient when used independently. Therefore, this study aimed to validate the usefulness of the phosphate-to-albumin ratio (PAR) in predicting neurological outcomes and in-hospital mortality by incorporating albumin, another known prognostic indicator. MATERIALS AND METHODS: This multicenter observational study included adult OHCA survivors from October 2015 to June 2021. The primary endpoint was an unfavorable neurological outcome at hospital discharge, defined as a cerebral performance category score of 3-5. The in-hospital mortality rates were also evaluated. RESULTS: Of the 2397 adult OHCA survivors, PAR differed significantly between the unfavorable and favorable neurological outcome groups, as well as between the non-survival and survival to hospital discharge groups (2.4 vs 1.4, 2.5 vs 1.6, respectively). The area under the receiver operating characteristic curve (AUROC) value of the PAR for predicting unfavorable neurological outcome was 0.81 (95% confidence interval [CI], 0.79-0.83), and the AUROC value for predicting in-hospital mortality was 0.76 (95% CI, 0.74-0.78). In multivariable analysis, the PAR was independently associated with unfavorable neurological outcome (odds ratio [OR] 1.30, 95% CI 1.15-1.37; p < 0.001) and in-hospital mortality (OR 1.24, 95% CI 1.12-1.38; p < 0.001). CONCLUSION: The PAR is a readily obtainable and independent prognostic indicator for patients with ROSC after OHCA, helping healthcare providers in predicting outcomes.

The usefulness of lactate/albumin ratio, C-reactive protein/albumin ratio, procalcitonin/albumin ratio, SOFA, and qSOFA in predicting the prognosis of patients with sepsis who presented to EDs.

PURPOSE: Early identification of sepsis with a poor prognosis in the emergency department (ED) is crucial for prompt management and improved outcomes. This study aimed to examine the predictive value of sequential organ failure assessment (SOFA), quick SOFA (qSOFA), lactate to albumin ratio (LAR), C-reactive protein to albumin ratio (CAR), and procalcitonin to albumin ratio (PAR), obtained in the ED, as predictors for 28-day mortality in patients with sepsis and septic shock. MATERIALS AND METHODS: We included 3499 patients (aged ≥19 years) from multicenter registry of the Korean Shock Society between October 2015 and December 2019. The SOFA score, qSOFA score, and lactate level at the time of registry enrollment were used. Albumin, C-reactive protein, and procalcitonin levels were obtained from the initial laboratory results measured upon ED arrival. We evaluated the predictive accuracy for 28-day mortality using the area under the receiver operating characteristic (AUROC) curve. A multivariable logistic regression analysis of the independent predictors of 28-day mortality was performed. The SOFA score, LAR, CAR, and PAR were converted to categorical variables using Youden's index and analyzed. Adjusting for confounding factors such as age, sex, comorbidities, and infection focus, adjusted odds ratios (aOR) were calculated. RESULTS: Of the 3499 patients, 2707 (77.4%) were survivors, whereas 792 (22.6%) were non-survivors. The median age of the patients was 70 (25th-75th percentiles, 61-78), and 2042 (58.4%) were male. LAR for predicting 28-day mortality had the highest AUROC, followed by the SOFA score (0.715; 95% confidence interval (CI): 0.69-0.74 and 0.669; 95% CI: 0.65-0.69, respectively). The multivariable logistic regression analysis revealed that the aOR of LAR >1.52 was 3.75 (95% CI: 3.16-4.45), and the aOR, of SOFA score at enrollment >7.5 was 2.67 (95% CI: 2.25-3.17). CONCLUSION: The results of this study showed that LAR is a relatively strong predictor of sepsis prognosis in the ED setting, indicating its potential as a straightforward and practical prognostic factor. This finding may assist healthcare providers in the ED by providing them with tools to risk-stratify patients and predict their mortality.

Targeting DNA polymerase to DNA double-strand breaks reduces DNA deletion size and increases templated insertions generated by CRISPR/Cas9.

Most insertions or deletions generated by CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9) endonucleases are short (<25 bp), but unpredictable on-target long DNA deletions (>500 bp) can be observed. The possibility of generating long on-target DNA deletions poses safety risks to somatic genome editing and makes the outcomes of genome editing less predictable. Methods for generating refined mutations are desirable but currently unavailable. Here, we show that fusing Escherichia coli DNA polymerase I or the Klenow fragment to Cas9 greatly increases the frequencies of 1-bp deletions and decreases >1-bp deletions or insertions. Importantly, doing so also greatly decreases the generation of long deletions, including those >2 kb. In addition, templated insertions (the insertion of the nucleotide 4 nt upstream of the protospacer adjacent motif) were increased relative to other insertions. Counteracting DNA resection was one of the mechanisms perturbing deletion sizes. Targeting DNA polymerase to double-strand breaks did not increase off-targets or base substitution rates around the cleavage sites, yet increased editing efficiency in primary cells. Our strategy makes it possible to generate refined DNA mutations for improved safety without sacrificing efficiency of genome editing.

Relationship Between High-Density Lipoprotein Cholesterol and Mortality in Elderly Hemodialysis Patients: Data From the Korean Society of Geriatric Nephrology Retrospective Cohort.

OBJECTIVES: The association between high-density lipoprotein (HDL) cholesterol levels and mortality in elderly patients undergoing hemodialysis is not well established. Thus, this study investigated HDL levels and mortality in elderly Korean patients undergoing hemodialysis. METHODS: We recruited 1860 incident hemodialysis patients aged greater than 70 years from a retrospective cohort of the Korean Society of Geriatric Nephrology. The primary outcome measure was all-cause mortality. RESULTS: The mean age of the cohort was 77.8 years, and 1049 (56.4%) were men. When we grouped the patients into HDL cholesterol tertiles, the T1 group (HDL level <30 mg/dL in men and <33 mg/dL in women) had a higher proportion of patients with end-stage kidney disease due to diabetic nephropathy. During the median follow-up period of 3.1 years, 1109 (59.7%) deaths occurred. In a multivariable Cox regression model, the T1 group had a significantly higher risk of mortality (hazard ratio [HR], 1.28; 95% confidence interval, 1.10-1.50; P = .002) compared to the T3 group. A nonlinear analysis using a restrictive spline curve showed that low HDL cholesterol levels were associated with increased HR when HDL cholesterol levels were <40 mg/dL; however, there was no association between HDL cholesterol and mortality when HDL cholesterol levels were >40 mg/dL. Triglyceride/HDL ratio was not significantly associated with the risk of mortality (HR per 1 log increase, 1.08; 95% confidence interval, 0.99-1.18; P = .069). CONCLUSIONS: Low HDL cholesterol levels are associated with an increased risk of mortality in elderly patients undergoing hemodialysis. However, there was no significant relationship between HDL cholesterol levels and mortality when levels were below 40 mg/dL. Therefore, low HDL cholesterol levels may be a useful risk factor for predicting mortality in elderly patients undergoing hemodialysis.

Early Cranioplasty in an Apert's Syndrome Infant With Occipital Encephalocele.

Apert's syndrome (AS) is a rare congenital malformation characterized by distinctive clinical manifestations such as syndactyly of the extremities and midface retrusion, which set it apart from other syndromes. This condition often presents with craniosynostosis and, less commonly, central nervous system abnormalities like encephalocele. In this report, we present a typical case of Apert syndrome with an occipital encephalocele. The infant had plagio-brachycephaly due to craniosynostosis and required urgent repair of the occipital encephalocele. At 1 month of age, we performed both the encephalocele repair and early cranioplasty for autologous bone grafting. This case underscores the importance of early diagnosis and surgical interventions in Apert's syndrome cases with encephalocele.

Hint from an Enzymatic Reaction: Superoxide Dismutase Models Efficiently Suppress Colorectal Cancer Cell Proliferation.

Superoxide dismutases (SODs) are essential antioxidant enzymes that prevent massive superoxide radical production and thus protect cells from damage induced by free radicals. However, this concept has rarely been applied to directly impede the function of driver oncogenes, thus far. Here, leveraging efforts from SOD model complexes, we report the novel finding of biomimetic copper complexes that efficiently scavenge intracellularly generated free radicals and, thereby, directly access the core consequence of colorectal cancer suppression. We conceived four structurally different SOD-mimicking copper complexes that showed distinct disproportionation reaction rates of intracellular superoxide radical anions. By replenishing SOD models, we observed a dramatic reduction of intracellular reactive oxygen species (ROS) and adenine 5'-triphosphate (ATP) concentrations that led to cell cycle arrest at the G2/M stage and induced apoptosis in vitro and in vivo. Our results showcase how nature-mimicking models can be designed and fine-tuned to serve as a viable chemotherapeutic strategy for cancer treatment.

Metformin Use and Long-term Clinical Outcomes in Kidney Transplant Recipients.

RATIONALE & OBJECTIVE: Metformin has been recommended for some patients with advanced chronic kidney disease. However, the value of metformin in kidney transplant recipients (KTRs) with pretransplant diabetes mellitus (DM) or posttransplant DM is uncertain. We investigated the clinical effects of metformin in KTRs. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: A total of 1,995 KTRs with diabetes from 6 tertiary referral centers in the Republic of Korea. EXPOSURE: Metformin usage was defined as the use of metformin for>90 days after kidney transplantation; 1,193 KTRs were metformin users, and 802 KTRs did not use metformin. Changing usage of metformin among those exposed for >90 days was also characterized. OUTCOME: Primary outcomes were all-cause mortality and death-censored graft failure (DCGF). Secondary outcomes were biopsy-proven acute rejection (BPAR) and lactic acidosis events. ANALYTICAL APPROACH: Survival analyses were conducted using multivariable Cox regression and competing risk analyses using Fine and Gray models. Changes in metformin use over time were modeled using a time-varying covariate. Metformin usage, mean daily dose, and hemoglobin A1c (HbA1c) changes were considered in the landmark analysis to address time-varying confounding. RESULTS: Metformin use was associated with a lower risk of DCGF (adjusted hazard ratio [AHR], 0.47 [95% CI, 0.23-0.96], P=0.038); there was no significant association with all-cause mortality (AHR, 0.94 [95% CI, 0.32-2.76], P=0.915) or BPAR (AHR 0.98 [95% CI, 0.62-1.54], P=0.942). In the subgroup analysis, metformin usage was associated with a reduced risk of all-cause mortality and a lower risk of DCGF for both pretransplantation DM and posttransplant DM groups. Metformin usage was associated with a lower risk of BPAR in the posttransplant DM group, although it was less effective in the pretransplantation DM group. There was no confirmed case of metformin-associated lactic acidosis (MALA) in the present cohort. A higher dose of metformin was correlated with lower risks of DCGF and BPAR. LIMITATIONS: Data on newer antidiabetic drugs such as SGLT2 inhibitors are limited, and there is potential limited generalizability to other populations. CONCLUSIONS: Metformin usage may benefit KTRs, as evidenced by its association with a reduced risk of DCGF and the absence of MALA events. Randomized controlled trials are needed to validate these observational findings.

Spin Dynamics Dominated by Resonant Tunneling into Molecular States.

Optical lattices and Feshbach resonances are two of the most ubiquitously used tools in atomic physics, allowing for the precise control, discrete confinement, and broad tunability of interacting atomic systems. Using a quantum simulator of lithium-7 atoms in an optical lattice, we investigate Heisenberg spin dynamics near a Feshbach resonance. We find novel resonance features in spin-spin interactions that can be explained only by lattice-induced resonances, which have never been observed before. We use these resonances to adiabatically convert atoms into molecules in excited bands. Lattice-induced resonances should be of general importance for studying strongly interacting quantum many-body systems in optical lattices.

Polymer-Lipid Hybrid Materials.

Hierarchic self-assembly underpins much of the form and function seen in synthetic or biological soft materials. Lipids are paramount examples, building themselves in nature or synthetically in a variety of meso/nanostructures. Synthetic block copolymers capture many of lipid's structural and functional properties. Lipids are typically biocompatible and high molecular weight polymers are mechanically robust and chemically versatile. The development of new materials for applications like controlled drug/gene/protein delivery, biosensors, and artificial cells often requires the combination of lipids and polymers. The emergent composite material, a "polymer-lipid hybrid membrane", displays synergistic properties not seen in pure components. Specific examples include the observation that hybrid membranes undergo lateral phase separation that can correlate in registry across multiple layers into a three-dimensional phase-separated system with enhanced permeability of encapsulated drugs. It is timely to underpin these emergent properties in several categories of hybrid systems ranging from colloidal suspensions to supported hybrid films. In this review, we discuss the form and function of a vast number of polymer-lipid hybrid systems published to date. We rationalize the results to raise new fundamental understanding of hybrid self-assembling soft materials as well as to enable the design of new supramolecular systems and applications.

Attenuation of Methane Oxidation by Nitrogen Availability in Arctic Tundra Soils.

CH4 emission in the Arctic has large uncertainty due to the lack of mechanistic understanding of the processes. CH4 oxidation in Arctic soil plays a critical role in the process, whereby removal of up to 90% of CH4 produced in soils by methanotrophs can occur before it reaches the atmosphere. Previous studies have reported on the importance of rising temperatures in CH4 oxidation, but because the Arctic is typically an N-limited system, fewer studies on the effects of inorganic nitrogen (N) have been reported. However, climate change and an increase of available N caused by anthropogenic activities have recently been reported, which may cause a drastic change in CH4 oxidation in Arctic soils. In this study, we demonstrate that excessive levels of available N in soil cause an increase in net CH4 emissions via the reduction of CH4 oxidation in surface soil in the Arctic tundra. In vitro experiments suggested that N in the form of NO3- is responsible for the decrease in CH4 oxidation via influencing soil bacterial and methanotrophic communities. The findings of our meta-analysis suggest that CH4 oxidation in the boreal biome is more susceptible to the addition of N than in other biomes. We provide evidence that CH4 emissions in Arctic tundra can be enhanced by an increase of available N, with profound implications for modeling CH4 dynamics in Arctic regions.

Association between food insecurity and risk of chronic diseases affecting the kidney in older Korean patients.

AIMS: This study aimed to examine the association between food insecurity and the prevalence of chronic diseases among older adults in South Korea and to compare the findings with data from the United States (US). MATERIALS AND METHODS: We analyzed data from the Korea National Health and Nutrition Examination Survey (KNHANES) V (2010 - 2012) and VI (2013 - 2015) and 4 years (2012 - 2015) of food security questionnaire data. The data of 46,189 National Health and Nutrition Examination Survey participants (1999 - 2016) were subjected to propensity score-matched (PSM) analysis. RESULTS: We included 7,914 individuals from the KNHANES. In the older group (age > 65 years), no differences were observed in the prevalence of hypertension, diabetes, chronic kidney disease (CKD), and metabolic syndrome across the income groups. Income, education, and food security had no impact on hypertension, diabetes, and CKD prevalence in the multivariate logistic analysis after PSM. CKD was not associated with food insecurity (odds ratio (OR), 1.26; 95% confidence interval (CI), 0.94 - 1.26) in the final model using the KNHANES data; however, the U.S. NHANES data showed that an increased risk of hypertension was associated with food insecurity (OR, 1.27; 95% CI, 1.04 - 1.55). CONCLUSION: As per the U.S. NHANES data, food insecurity was associated with a high prevalence of hypertension, while as per the South Korean KNHANES data, food insecurity was not found to be associated with CKD, indicating divergent relationships between food insecurity and chronic diseases in the two countries. Further research is needed to explore these differences.

Multisample Mass Spectrometry-Based Approach for Discovering Injury Markers in Chronic Kidney Disease.

Urinary proteomics studies have primarily focused on identifying markers of chronic kidney disease (CKD) progression. Here, we aimed to determine urinary markers of CKD renal parenchymal injury through proteomics analysis in animal kidney tissues and cells and in the urine of patients with CKD. Label-free quantitative proteomics analysis based on liquid chromatography-tandem mass spectrometry was performed on urine samples obtained from 6 normal controls and 9, 11, and 10 patients with CKD stages 1, 3, and 5, respectively, and on kidney tissue samples from a rat CKD model by 5/6 nephrectomy. Tandem mass tag-based quantitative proteomics analysis was performed for glomerular endothelial cells (GECs) and proximal tubular epithelial cells (PTECs) before and after inducing 24-h hypoxia injury. Upon hierarchical clustering, out of 858 differentially expressed proteins (DEPs) in the urine of CKD patients, the levels of 416 decreased and 403 increased sequentially according to the disease stage, respectively. Among 2965 DEPs across 5/6 nephrectomized and sham-operated rat kidney tissues, 86 DEPs showed same expression patterns in the urine and kidney tissue. After cross-validation with two external animal proteome data sets, 38 DEPs were organized; only ten DEPs, including serotransferrin, gelsolin, poly ADP-ribose polymerase 1, neuroblast differentiation-associated protein AHNAK, microtubule-associated protein 4, galectin-1, protein S, thymosin beta-4, myristoylated alanine-rich C-kinase substrate, and vimentin, were finalized by screening human GECs and PTECs data. Among these ten potential candidates for universal CKD marker, validation analyses for protein S and galectin-1 were conducted. Galectin-1 was observed to have a significant inverse correlation with renal function as well as higher expression in glomerulus with chronic injury than protein S. This constitutes the first multisample proteomics study for identifying key renal-expressed proteins associated with CKD progression. The discovered proteins represent potential markers of chronic renal cell and tissue damage and candidate contributors to CKD pathophysiology.

Diagnostic performance of rapid antigen tests for SARS-CoV-2 transmission risk based on cycle threshold values in the emergency department.

BACKGROUND: This study aimed to investigate the diagnostic performance of the rapid antigen test (RAT) for screening patients with cycle threshold (Ct) values of SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) in the emergency department. Previous studies have shown that Ct values could be used as indicators of infectiousness. Therefore, we considered the Ct value an indicator of potential infectiousness. METHODS: This single-center retrospective observational study was conducted between January 1, 2020, and March 31, 2022. Patients who underwent both RT-PCR and RAT for the diagnosis of COVID-19 were included. Patients with negative RT-PCR results were excluded. Patients with Ct values lower than 26 and 30 were considered potentially infectious for COVID-19. RESULT: A total of 386 patients were analyzed. At Ct value cutoffs of 26 and 30, the result of the RAT showed a sensitivity of 82% and 74%, specificity of 84% and 89%, and area under the curve (AUC) of 0.829 and 0.813, respectively, in the receiver operating characteristic curve. However, the NPV was relatively low at 55% and 25%. CONCLUSION: The RAT might be a rapid screening tool for detecting patients with the infectiousness of SARS-CoV-2. However, considering the low NPV, it is challenging to depend only on a negative test result from an antigen test to terminate quarantine. Clinicians should consider additional factors, such as the duration of symptoms and the immunocompromised state, for SARS-CoV-2 transmission.