Generation of a human induced pluripotent stem cell line (YUCMi020-A) from peripheral blood mononuclear cells derived from a female with the Jr(a-) blood type.

The Jra antigen, the only antigen within the JR blood group system, is a high-prevalence red blood cell (RBC) antigen found in over 99 % of the global population. An induced pluripotent stem cell line (YUCMi020-A) was generated from peripheral blood drawn from a Jr(a-) phenotype individual, who was homozygous for a null mutation of ABCG2*01N.01 (rs72552713, c.376C>T; p.Gln126*). The generated line exhibited pluripotent characteristics and no chromosomal aberrations. This cell line will serve as a cell source, enabling us to produce RBCs with the Jr(a-) phenotype in vitro, which can be used for transfusing individuals with anti-Jra antibodies.

Multi-ancestry polygenic mechanisms of type 2 diabetes.

Type 2 diabetes (T2D) is a multifactorial disease with substantial genetic risk, for which the underlying biological mechanisms are not fully understood. In this study, we identified multi-ancestry T2D genetic clusters by analyzing genetic data from diverse populations in 37 published T2D genome-wide association studies representing more than 1.4 million individuals. We implemented soft clustering with 650 T2D-associated genetic variants and 110 T2D-related traits, capturing known and novel T2D clusters with distinct cardiometabolic trait associations across two independent biobanks representing diverse genetic ancestral populations (African, n = 21,906; Admixed American, n = 14,410; East Asian, n =2,422; European, n = 90,093; and South Asian, n = 1,262). The 12 genetic clusters were enriched for specific single-cell regulatory regions. Several of the polygenic scores derived from the clusters differed in distribution among ancestry groups, including a significantly higher proportion of lipodystrophy-related polygenic risk in East Asian ancestry. T2D risk was equivalent at a body mass index (BMI) of 30 kg m-2 in the European subpopulation and 24.2 (22.9-25.5) kg m-2 in the East Asian subpopulation; after adjusting for cluster-specific genetic risk, the equivalent BMI threshold increased to 28.5 (27.1-30.0) kg m-2 in the East Asian group. Thus, these multi-ancestry T2D genetic clusters encompass a broader range of biological mechanisms and provide preliminary insights to explain ancestry-associated differences in T2D risk profiles.

Child and adolescent participation measurement tools and their translations: A systematic review.

BACKGROUND: Numerous participation measurement tools targeting children and youth have been developed. Despite the translation of these tools into specific languages and cultures, the reliability and validity of the translated versions remain uncertain. To address this gap in knowledge, this study aims to identify tools for assessing the participation of children aged 5-18 years and to appraise the psychometric properties of their translated versions. METHODS: Four electronic databases were searched for peer-reviewed studies published in English. Preferred Reporting Items for Systematic Reviews guidelines was followed. Study titles and abstracts were screened by four independent reviewers. Data were extracted for both original and translated versions of eligible tools. Instrument quality assessments were performed using the Outcome Measures Rating Form Guidelines. Any discrepancies were resolved by consensus. RESULTS: Out of the 31 measurement tools examined, 18 tools had at least one translated version available, and among those original measurement tools, a total of 58 translated versions were identified. The most widely translated tool was the Physical Activity Questionnaire for Children (12 languages), and the most frequently translated language was Chinese (7 tools). Most translated versions verified internal consistency and content validity. Only three translated versions were verified inter-rater reliability, and seven translated versions were tested criterion validity with the gold standard tools assessing participation of children (e.g., accelerometer, Pediatric Evaluation of Disability Inventory and four 24-h recalls). None of the translated versions were tested for intra-rater reliability and responsiveness. CONCLUSIONS: These findings can support the selection of psychometrically sound tools for children with disabilities, given their culture and language, and tool quality.

Angiogenesis-on-a-chip coupled with single-cell RNA sequencing reveals spatially differential activations of autophagy along angiogenic sprouts.

Several functions of autophagy associated with proliferation, differentiation, and migration of endothelial cells have been reported. Due to lack of models recapitulating angiogenic sprouting, functional heterogeneity of autophagy in endothelial cells along angiogenic sprouts remains elusive. Here, we apply an angiogenesis-on-a-chip to reconstruct 3D sprouts with clear endpoints. We perform single-cell RNA sequencing of sprouting endothelial cells from our chip to reveal high activation of autophagy in two endothelial cell populations- proliferating endothelial cells in sprout basements and stalk-like endothelial cells near sprout endpoints- and further the reciprocal expression pattern of autophagy-related genes between stalk- and tip-like endothelial cells near sprout endpoints, implying an association of autophagy with tip-stalk cell specification. Our results suggest a model describing spatially differential roles of autophagy: quality control of proliferating endothelial cells in sprout basements for sprout elongation and tip-stalk cell specification near sprout endpoints, which may change strategies for developing autophagy-based anti-angiogenic therapeutics.

Polycystic Ovary Syndrome Physiologic Pathways Implicated Through Clustering of Genetic Loci.

CONTEXT: Polycystic ovary syndrome (PCOS) is a heterogeneous disorder, with disease loci identified from genome-wide association studies (GWAS) having largely unknown relationships to disease pathogenesis. OBJECTIVE: This work aimed to group PCOS GWAS loci into genetic clusters associated with disease pathophysiology. METHODS: Cluster analysis was performed for 60 PCOS-associated genetic variants and 49 traits using GWAS summary statistics. Cluster-specific PCOS partitioned polygenic scores (pPS) were generated and tested for association with clinical phenotypes in the Mass General Brigham Biobank (MGBB, N = 62 252). Associations with clinical outcomes (type 2 diabetes [T2D], coronary artery disease [CAD], and female reproductive traits) were assessed using both GWAS-based pPS (DIAMANTE, N = 898,130, CARDIOGRAM/UKBB, N = 547 261) and individual-level pPS in MGBB. RESULTS: Four PCOS genetic clusters were identified with top loci indicated as following: (i) cluster 1/obesity/insulin resistance (FTO); (ii) cluster 2/hormonal/menstrual cycle changes (FSHB); (iii) cluster 3/blood markers/inflammation (ATXN2/SH2B3); (iv) cluster 4/metabolic changes (MAF, SLC38A11). Cluster pPS were associated with distinct clinical traits: Cluster 1 with increased body mass index (P = 6.6 × 10-29); cluster 2 with increased age of menarche (P = 1.5 × 10-4); cluster 3 with multiple decreased blood markers, including mean platelet volume (P = 3.1 ×10-5); and cluster 4 with increased alkaline phosphatase (P = .007). PCOS genetic clusters GWAS-pPSs were also associated with disease outcomes: cluster 1 pPS with increased T2D (odds ratio [OR] 1.07; P = 7.3 × 10-50), with replication in MGBB all participants (OR 1.09, P = 2.7 × 10-7) and females only (OR 1.11, 4.8 × 10-5). CONCLUSION: Distinct genetic backgrounds in individuals with PCOS may underlie clinical heterogeneity and disease outcomes.

Five-Day Spacing of Two Fractionated Ablative Radiotherapies Enhances Antitumor Immunity.

PURPOSE: This study aimed to enhance tumor control and abscopal effects by applying diverse stereotactic ablative radiation therapy (SABR) schedules. METHODS AND MATERIALS: FSaII, CT-26, and 4T1 cells were used for tumor growth delay and lung metastases analysis after 1- or 5-day intervals radiation therapy (RT) with 40, 20, and 20 Gy, respectively. Immunodeficient BALB/c-nude, immunocompetent C3H, and BALB/c mouse models were used. For immune monitoring, FSaII tumors were analyzed using flow cytometry, immunofluorescence staining, and real-time quantitative reverse transcription polymerase chain reaction. The spleens were used for the ELISpot assay and flow cytometry to determine effector CD8 T cells. For abscopal effect analysis in CT-26 tumors, the volume of the nonirradiated secondary tumors was measured after primary tumors were irradiated with 1-day or 5-day intervals. RESULTS: Contrary to the high-dose 1-day interval RT, the 5-day interval RT significantly delayed tumor growth in immunocompetent mice, which was not observed in immunodeficient mice. In addition, the 5-day interval RT significantly reduced the number of lung metastases in FSaII and CT-26 tumors. Five-day spacing was more effective than 1-day interval in enhancing the antitumor immunity via increasing the secretion of tumor-specific IFN-γ, activating the CD8 T cells, and suppressing the monocytic myeloid-derived suppressor cells. The 5-day spacing inhibited nonirradiated secondary tumor growth more effectively than did the 1-day interval. CONCLUSIONS: Compared with the 1-day interval RT, the 5-day interval RT scheme demonstrated enhanced antitumor immunity of CD8 T cells associated with inhibition of myeloid-derived suppressor cells. Enhancing antitumor immunity leads to significant improvements in both primary tumor control and the abscopal effect.

Coupled adsorption-photocatalysis process for the removal of diclofenac using magnetite/reduced graphene oxide nanocomposite.

Diclofenac (DCF) is frequently detected in water bodies (ng/L to g/L) as it is not completely removed by conventional wastewater treatment plants. Adsorption and photocatalysis have been studied as promising methods for treating DCF; however, both processes have limitations. Thus, in this study, the removal efficiency of DCF is evaluated using a magnetite/reduced graphene oxide (Fe3O4/RGO) nanocomposite via a coupled adsorption-catalysis process. The Fe3O4/RGO nanocomposite was successfully synthesized using a microwave-assisted solvothermal method and exhibited a bandgap of 2.60 eV. The kinetic data best fitted the Elovich model (R2 = 0.994, χ2 = 0.29), indicating rapid adsorption. The maximum DCF adsorption capacity calculated using the Langmuir model was 80.33 mg/g. An ultraviolet C (UVC) light source and 0.1 g/L of Fe3O4/RGO nanocomposite were the optimum conditions for the removal of DCF (C0 = 30 mM) by a coupled adsorption-photocatalysis process (first-order rate constant (k) = 0.088/min), which was greater than the single adsorption (k = 0.029/min) and pre-adsorption and post-photocatalysis (k = 0.053/min) processes. This indicates that the adsorbed DCF did not hamper the photocatalytic reaction of the Fe3O4/RGO nanocomposite, but rather enhanced the coupled adsorption-photocatalytic reaction. DCF removal efficiency was higher at acidic conditions (pH 4.3-5.0), because high H+ promotes the generation of certain reactive oxygen species (ROS) and increases of electrostatic interaction. The presence of NaCl and CaCl2 (10 mM) did not notably affect the total DCF removal efficiency; however, Ca2+ affected the initial DCF adsorption affinity. Scavenger experiments demonstrated O2∙- and h+ play a key ROS than ·OH to degrade DCF. The acute toxicity of DCF towards Aliivibrio fischeri gradually decreased with increasing treatment time.

Activation of Lysosomal Function Ameliorates Amyloid-ß-Induced Tight Junction Disruption in the Retinal Pigment Epithelium.

Accumulation of pathogenic amyloid-ß disrupts the tight junction of retinal pigment epithelium (RPE), one of its senescence-like structural alterations. In the clearance of amyloid-ß, the autophagy-lysosome pathway plays the crucial role. In this context, mammalian target of rapamycin (mTOR) inhibits the process of autophagy and lysosomal degradation, acting as a potential therapeutic target for age-associated disorders. However, efficacy of targeting mTOR to treat age-related macular degeneration remains largely elusive. Here, we validated the therapeutic efficacy of the mTOR inhibitors, Torin and PP242, in clearing amyloid-ß by inducing the autophagy-lysosome pathway in a mouse model with pathogenic amyloid-ß with tight junction disruption of RPE, which is evident in dry age-related macular degeneration. High concentration of amyloid-ß oligomers induced autophagy-lysosome pathway impairment accompanied by the accumulation of p62 and decreased lysosomal activity in RPE cells. However, Torin and PP242 treatment restored the lysosomal activity via activation of LAMP2 and facilitated the clearance of amyloid-ß in vitro and in vivo. Furthermore, clearance of amyloid-ß by Torin and PP242 ameliorated the tight junction disruption of RPE in vivo. Overall, our findings suggest mTOR inhibition as a new therapeutic strategy for the restoration of tight junctions in age-related macular degeneration.

Heterogeneous effects on type 2 diabetes and cardiovascular outcomes of genetic variants and traits associated with fasting insulin.

Hyperinsulinemia is a complex and heterogeneous phenotype that characterizes molecular alterations that precede the development of type 2 diabetes (T2D). It results from a complex combination of molecular processes, including insulin secretion and insulin sensitivity, that differ between individuals. To better understand the physiology of hyperinsulinemia and ultimately T2D, we implemented a genetic approach grouping fasting insulin (FI)-associated genetic variants based on their molecular and phenotypic similarities. We identified seven distinctive genetic clusters representing different physiologic mechanisms leading to rising FI levels, ranging from clusters of variants with effects on increased FI, but without increased risk of T2D (non-diabetogenic hyperinsulinemia), to clusters of variants that increase FI and T2D risk with demonstrated strong effects on body fat distribution, liver, lipid, and inflammatory processes (diabetogenic hyperinsulinemia). We generated cluster-specific polygenic scores in 1,104,258 individuals from five multi-ancestry cohorts to show that the clusters differed in associations with cardiometabolic traits. Among clusters characterized by non-diabetogenic hyperinsulinemia, there was both increased and decreased risk of coronary artery disease despite the non-increased risk of T2D. Similarly, the clusters characterized by diabetogenic hyperinsulinemia were associated with an increased risk of T2D, yet had differing risks of cardiovascular conditions, including coronary artery disease, myocardial infarction, and stroke. The strongest cluster-T2D associations were observed with the same direction of effect in non-Hispanic Black, Hispanic, non-Hispanic White, and non-Hispanic East Asian populations. These genetic clusters provide important insights into granular metabolic processes underlying the physiology of hyperinsulinemia, notably highlighting specific processes that decouple increasing FI levels from T2D and cardiovascular risk. Our findings suggest that increasing FI levels are not invariably associated with adverse cardiometabolic outcomes.

Multi-ancestry Polygenic Mechanisms of Type 2 Diabetes Elucidate Disease Processes and Clinical Heterogeneity.

We identified genetic subtypes of type 2 diabetes (T2D) by analyzing genetic data from diverse groups, including non-European populations. We implemented soft clustering with 650 T2D-associated genetic variants, capturing known and novel T2D subtypes with distinct cardiometabolic trait associations. The twelve genetic clusters were distinctively enriched for single-cell regulatory regions. Polygenic scores derived from the clusters differed in distribution between ancestry groups, including a significantly higher proportion of lipodystrophy-related polygenic risk in East Asian ancestry. T2D risk was equivalent at a BMI of 30 kg/m2 in the European subpopulation and 24.2 (22.9-25.5) kg/m2 in the East Asian subpopulation; after adjusting for cluster-specific genetic risk, the equivalent BMI threshold increased to 28.5 (27.1-30.0) kg/m2 in the East Asian group, explaining about 75% of the difference in BMI thresholds. Thus, these multi-ancestry T2D genetic subtypes encompass a broader range of biological mechanisms and help explain ancestry-associated differences in T2D risk profiles.

Multi-ancestry Polygenic Mechanisms of Type 2 Diabetes Elucidate Disease Processes and Clinical Heterogeneity.

We identified genetic subtypes of type 2 diabetes (T2D) by analyzing genetic data from diverse groups, including non-European populations. We implemented soft clustering with 650 T2D-associated genetic variants, capturing known and novel T2D subtypes with distinct cardiometabolic trait associations. The twelve genetic clusters were distinctively enriched for single-cell regulatory regions. Polygenic scores derived from the clusters differed in distribution between ancestry groups, including a significantly higher proportion of lipodystrophy-related polygenic risk in East Asian ancestry. T2D risk was equivalent at a BMI of 30 kg/m2 in the European subpopulation and 24.2 (22.9-25.5) kg/m2 in the East Asian subpopulation; after adjusting for cluster-specific genetic risk, the equivalent BMI threshold increased to 28.5 (27.1-30.0) kg/m2 in the East Asian group, explaining about 75% of the difference in BMI thresholds. Thus, these multi-ancestry T2D genetic subtypes encompass a broader range of biological mechanisms and help explain ancestry-associated differences in T2D risk profiles.

Microlens array camera with variable apertures for single-shot high dynamic range (HDR) imaging.

We report a microlens array camera with variable apertures (MACVA) for high dynamic range (HDR) imaging by using microlens arrays with various sizes of apertures. The MACVA comprises variable apertures, microlens arrays, gap spacers, and a CMOS image sensor. The microlenses with variable apertures capture low dynamic range (LDR) images with different f-stops under single-shot exposure. The reconstructed HDR images clearly exhibit expanded dynamic ranges surpassing LDR images as well as high resolution without motion artifacts, comparable to the maximum MTF50 value observed among the LDR images. This compact camera provides, what we believe to be, a new perspective for various machine vision or mobile devices applications.

3D Porous Cu-Composites for Stable Li-Metal Battery Anodes.

Lithium (Li) metal is a promising anode material for lithium-ion batteries (LIBs) because of its high theoretical specific capacity of 3860 mAh g-1 and the low potential of -3.04 V versus the standard hydrogen electrode (SHE). However, these anodes rely on repeated plating and stripping of Li, which leads to consumption of Li inventory and the growth of dendrites that can lead to self-discharge and safety issues. To address these issues, as well as problems related to the volume change of these anodes, a number of different porous conductive scaffolds have been reported to create high surface area electrode on which Li can be plated reliably. While impressive results have been reported in literature, current processes typically rely on either expensive or poorly scalable techniques. Herein, we report a scalable fabrication method to create robust 3D Cu anodes using a one-step electrodeposition process. The areal loading, pore structure, and electrode thickness can be tuned by changing the electrodeposition parameters, and we show how standard mechanical calendering provides a way to further optimize electrode volume, capacity, and cycling stability. Optimized electrodes achieve high Coulombic efficiencies (CEs) of 99% during 800 cycles in half cells at a current density of 0.5 mA cm-2 with a total capacity of 0.5 mAh cm-2. To the best of our knowledge, this is the highest value ever reported for a host for Li-metal anodes using lithium bis(trifluoromethanesulfonyl)imide LITFSI based electrolyte.

Inhibition of protein arginine deiminase II suppresses retinoblastoma in orthotopic transplantation in mice.

Chemotherapies are used for treating retinoblastoma; however, numerous patients suffer from recurrence or symptoms due to chemotherapy, which emphasizes the need for alternative therapeutic strategies. The present study demonstrated that protein arginine deiminase Ⅱ (PADI2) was highly expressed in human and mouse retinoblastoma tissues due to the overexpression of E2 factor (E2F). By inhibiting PADI2 activity, the expression of phosphorylated AKT was reduced, and cleaved poly (ADP­ribose) polymerase level was increased, leading to induced apoptosis. Similar results were obtained in orthotopic mouse models with reduced tumor volumes. In addition, BB­Cl­amidine showed low toxicity in vivo. These results suggested that PADI2 inhibition has potential clinical translation. Furthermore, the present study highlights the potential of epigenetic approaches to target RB1­deficient mutations at the molecular level. The current findings provide new insights into the importance of retinoblastoma intervention by managing PADI2 activity according to the treatment of specific inhibitors and depletion approaches in vitro and in orthotopic mouse models.

PHGDH preserves one-carbon cycle to confer metabolic plasticity in chemoresistant gastric cancer during nutrient stress.

Molecular classification of gastric cancer (GC) identified a subgroup of patients showing chemoresistance and poor prognosis, termed SEM (Stem-like/Epithelial-to-mesenchymal transition/Mesenchymal) type in this study. Here, we show that SEM-type GC exhibits a distinct metabolic profile characterized by high glutaminase (GLS) levels. Unexpectedly, SEM-type GC cells are resistant to glutaminolysis inhibition. We show that under glutamine starvation, SEM-type GC cells up-regulate the 3 phosphoglycerate dehydrogenase (PHGDH)-mediated mitochondrial folate cycle pathway to produce NADPH as a reactive oxygen species scavenger for survival. This metabolic plasticity is associated with globally open chromatin structure in SEM-type GC cells, with ATF4/CEBPB identified as transcriptional drivers of the PHGDH-driven salvage pathway. Single-nucleus transcriptome analysis of patient-derived SEM-type GC organoids revealed intratumoral heterogeneity, with stemness-high subpopulations displaying high GLS expression, a resistance to GLS inhibition, and ATF4/CEBPB activation. Notably, coinhibition of GLS and PHGDH successfully eliminated stemness-high cancer cells. Together, these results provide insight into the metabolic plasticity of aggressive GC cells and suggest a treatment strategy for chemoresistant GC patients.

Feeding Behavior Comparison of Bean Bugs, Riptortus pedestris and Halyomorpha halys on Different Soybean Cultivars.

Riptortus pedestris (Fabricius) and Halyomorpha halys (Stål) are the major pests that feed on soybean pods, seeds, and fruits. Higher populations and damage occur during the soybean maturity stages (podding to harvest). To compare the feeding behavior of R. pedestris and H. halys, we used the six most cultivated cultivars (Daepung-2ho, Daechan, Pungsannamul, Daewon, Seonpung, and Seoritae) in Korea using the electropenetrography (EPG) technique. Both R. pedestris and H. halys, the NP (non-penetration), a non-probing waveform, was the shortest in the Pungsannamul (298 and 268 min) and the longest in the Daepung-2ho (334 and 339 min), respectively. The feeding waveforms Pb (phloem feeding: E1-Salivation and E2-Sap feeding) and G (xylem feeding) were the longest in Pungsannamul and the shortest in Daepung-2ho. In addition, as a result of investigating the damage rate by planting six cultivars of beans in the field, as expected, the proportions of damage types B and C were highest in Pungsannamul and lowest in Daepung-2ho. These results reveal that both bug species ingest xylem sap from leaflets and stems using a salivary sheath strategy to acquire water and nutrients from soybean pods/seeds with cell-rupture tactics. This study provides perceptive information to understand the feeding behavior, field occurrence, and damage patterns of R. pedestris and H. halys, which may have key implications for the management of hemipteran pests by determining the specificity and susceptibility of host plants.

In vitro erythrocyte production using human-induced pluripotent stem cells: determining the best hematopoietic stem cell sources.

BACKGROUND: Blood transfusion is an essential part of medicine. However, many countries have been facing a national blood crisis. To address this ongoing blood shortage issue, there have been efforts to generate red blood cells (RBCs) in vitro, especially from human-induced pluripotent stem cells (hiPSCs). However, the best source of hiPSCs for this purpose is yet to be determined. METHODS: In this study, hiPSCs were established from three different hematopoietic stem cell sources-peripheral blood (PB), cord blood (CB) and bone marrow (BM) aspirates (n = 3 for each source)-using episomal reprogramming vectors and differentiated into functional RBCs. Various time-course studies including immunofluorescence assay, quantitative real-time PCR, flow cytometry, karyotyping, morphological analysis, oxygen binding capacity analysis, and RNA sequencing were performed to examine and compare the characteristics of hiPSCs and hiPSC-differentiated erythroid cells. RESULTS: hiPSC lines were established from each of the three sources and were found to be pluripotent and have comparable characteristics. All hiPSCs differentiated into erythroid cells, but there were discrepancies in differentiation and maturation efficiencies: CB-derived hiPSCs matured into erythroid cells the fastest while PB-derived hiPSCs required a longer time for maturation but showed the highest degree of reproducibility. BM-derived hiPSCs gave rise to diverse types of cells and exhibited poor differentiation efficiency. Nonetheless, erythroid cells differentiated from all hiPSC lines mainly expressed fetal and/or embryonic hemoglobin, indicating that primitive erythropoiesis occurred. Their oxygen equilibrium curves were all left-shifted. CONCLUSIONS: Collectively, both PB- and CB-derived hiPSCs were favorably reliable sources for the clinical production of RBCs in vitro, despite several challenges that need to be overcome. However, owing to the limited availability and the large amount of CB required to produce hiPSCs, and the results of this study, the advantages of using PB-derived hiPSCs for RBC production in vitro may outweigh those of using CB-derived hiPSCs. We believe that our findings will facilitate the selection of optimal hiPSC lines for RBC production in vitro in the near future.

Epigenetic regulation of autophagy by histone-modifying enzymes under nutrient stress.

Autophagy is an evolutionarily conserved catabolic process that is induced in response to various stress factors in order to protect cells and maintain cellular homeostasis by degrading redundant components and dysfunctional organelles. Dysregulation of autophagy has been implicated in several conditions such as cancer, neurodegenerative diseases, and metabolic disorders. Although autophagy has been commonly considered as a cytoplasmic process, accumulating evidence has revealed that epigenetic regulation within the nucleus is also important for regulation of autophagy. In particular, when energy homeostasis is disrupted, for instance due to nutrient deprivation, cells increase autophagic activity at the transcriptional level, thereby also increasing the extent of overall autophagic flux. The transcription of genes associated with autophagy is strictly regulated by epigenetic factors through a network of histone-modifying enzymes along with histone modifications. A better understanding of the complex regulatory mechanisms of autophagy could reveal potential new therapeutic targets for autophagy-related diseases. In this review, we discuss the epigenetic regulation of autophagy in response to nutrient stress, focusing on histone-modifying enzymes and histone modifications.

Triglyceride induces DNA damage leading to monocyte death by activating caspase-2 and caspase-8.

Monocytes are peripheral leukocytes that function in innate immunity. Excessive triglyceride (TG) accumulation causes monocyte death and thus can compromise innate immunity. However, the mechanisms by which TG mediates monocyte death remain unclear to date. Thus, this study aimed to elucidate the mechanisms by which TG induces monocyte death. Results showed that TG induced monocyte death by activating caspase-3/7 and promoting poly (ADP-ribose) polymerase (PARP) cleavage. In addition, TG induced DNA damage and activated the ataxia telangiectasia mutated (ATM)/checkpoint kinase 2 and ATM-and Rad3-related (ATR)/checkpoint kinase 1 pathways, leading to the cell death. Furthermore, TG-induced DNA damage and monocyte death were mediated by caspase-2 and -8, and caspase-8 acted as an upstream molecule of caspase-2. Taken together, these results suggest that TG-induced monocyte death is mediated via the caspase-8/caspase-2/DNA damage/executioner caspase/PARP pathways. [BMB Reports 2023; 56(3): 166-171].