Diagnostic Performance of Insulin Resistance Indices for Identifying Metabolic Dysfunction-Associated Fatty Liver Disease.

Background/objectives: Insulin resistance (IR) plays an important role in metabolic dysfunction-associated fatty liver disease (MAFLD) pathogenesis. A modified triglyceride-glucose (TyG) index, including TyG-body mass index (TyG-BMI) and TyG-waist circumference (TyG-WC), has been introduced to represent IR. This study aimed to investigate the diagnostic abilities of IR indices in MAFLD, in which fatty liver was diagnosed using computed tomography (CT). Subjects/methods: We retrospectively analyzed the clinical data and images of 852 adults aged ≥19 years who underwent abdominal CT. MAFLD was diagnosed based on the appearance of fatty liver on CT alongside at least one of the following three criteria: being overweight or obese, at least two metabolic risk abnormalities, and/or diabetes mellitus. IR indices were calculated by examining the following variables: homeostasis model assessment-IR, TyG index, TyG-BMI, TyG-WC, and visceral adiposity index. The diagnostic accuracy was evaluated using the area under the receiver operating characteristic curve. Results: For all patients, the area under the curve (AUC) of the TyG index, TyG-BMI, and TyG-WC were 0.834, 0.938, and 0.942, respectively. In men, the AUC of the TyG index, TyG-BMI, and TyG-WC were 0.812, 0.928, and 0.934, respectively. In women, the AUC of the TyG index was 0.841, and TyG-BMI and TyG-WC were 0.940 and 0.953, respectively. The AUC values tended to increase in the following order: TyG index < TyG-BMI < TyG-WC. Women showed a higher AUC than men in all items, and the TyG-WC of women showed the highest value with AUC 0.953 (95% confidence interval [CI]: 0.892-1.000, P < 0.0001). The AUC of the TyG index was 0.858 (95% CI: 0.828-0.888, P < 0.0001). Conclusions: In conclusion, TyG-WC is a powerful surrogate marker for identifying MAFLD in clinical settings.

Genome-wide methylation landscape during somatic embryogenesis in Medicago truncatula reveals correlation between Tnt1 retrotransposition and hyperactive methylation regions.

Medicago truncatula is a model legume for fundamental research on legume biology and symbiotic nitrogen fixation. Tnt1, a retrotransposon from tobacco, was used to generate insertion mutants in M. truncatula R108. Approximately 21 000 insertion lines have been generated and publicly available. Tnt1 retro-transposition event occurs during somatic embryogenesis (SE), a pivotal process that triggers massive methylation changes. We studied the SE of M. truncatula R108 using leaf explants and explored the dynamic shifts in the methylation landscape from leaf explants to callus formation and finally embryogenesis. Higher cytosine methylation in all three contexts of CG, CHG, and CHH patterns was observed during SE compared to the controls. Higher methylation patterns were observed in assumed promoter regions (~2-kb upstream regions of transcription start site) of the genes, while lowest was recorded in the untranslated regions. Differentially methylated promoter region analysis showed a higher CHH methylation in embryogenesis tissue samples when compared to CG and CHG methylation. Strong correlation (89.71%) was identified between the differentially methylated regions (DMRs) and the site of Tnt1 insertions in M. truncatula R108 and stronger hypermethylation of genes correlated with higher number of Tnt1 insertions in all contexts of CG, CHG, and CHH methylation. Gene ontology enrichment and KEGG pathway enrichment analysis identified genes and pathways enriched in the signal peptide processing, ATP hydrolysis, RNA polymerase activity, transport, secondary metabolites, and nitrogen metabolism pathways. Combined gene expression analysis and methylation profiling showed an inverse relationship between methylation in the DMRs (regions spanning genes) and the expression of genes. Our results show that a dynamic shift in methylation happens during the SE process in the context of CG, CHH and CHG methylation, and the Tnt1 retrotransposition correlates with the hyperactive methylation regions.

The peptide GOLVEN10 alters root development and noduletaxis in Medicago truncatula.

The conservation of GOLVEN (GLV)/ROOT MERISTEM GROWTH FACTOR (RGF) peptide encoding genes across plant genomes capable of forming roots or root-like structures underscores their potential significance in the terrestrial adaptation of plants. This study investigates the function and role of GOLVEN peptide-coding genes in Medicago truncatula. Five out of fifteen GLV/RGF genes were notably upregulated during nodule organogenesis and were differentially responsive to nitrogen deficiency and auxin treatment. Specifically, the expression of MtGLV9 and MtGLV10 at nodule initiation sites was contingent upon the NODULE INCEPTION transcription factor. Overexpression of these five nodule-induced GLV genes in hairy roots of M. truncatula and application of their synthetic peptide analogues led to a decrease in nodule count by 25-50%. Uniquely, the GOLVEN10 peptide altered the positioning of the first formed lateral root and nodule on the primary root axis, an observation we term 'noduletaxis'; this decreased the length of the lateral organ formation zone on roots. Histological section of roots treated with synthetic GOLVEN10 peptide revealed an increased cell number within the root cortical cell layers without a corresponding increase in cell length, leading to an elongation of the root likely introducing a spatiotemporal delay in organ formation. At the transcription level, the GOLVEN10 peptide suppressed expression of microtubule-related genes and exerted its effects by changing expression of a large subset of Auxin responsive genes. These findings advance our understanding of the molecular mechanisms by which GOLVEN peptides modulate root morphology, nodule ontogeny, and interactions with key transcriptional pathways.

Precise sensorimotor control impacts reproductive fitness of C. elegans in 3D environments.

The ability of animals to sense and navigate towards relevant cues in complex and elaborate habitats is paramount for their survival and reproductive success. The nematode Caenorhabditis elegans uses a simple and elegant sensorimotor program to track odors in its environments. Whether this allows the worm to effectively navigate a complex environment and increase its evolutionary success has not been tested yet. We designed an assay to test whether C. elegans can track odors in a complex 3D environment. We then used a previously established 3D cultivation system to test whether defect in tracking odors to find food in a complex environment affected their brood size. We found that wild-type worms can accurately migrate toward a variety of odors in 3D. However, mutants of the muscarinic acetylcholine receptor GAR-3 which have a sensorimotor integration defect that results in a subtle navigational defect steering towards attractive odors, display decreased chemotaxis to the odor butanone not seen in the traditional 2D assay. We also show that the decreased ability to locate appetitive stimuli in 3D leads to reduced brood size not observed in the standard 2D culture conditions. Our study shows that mutations in genes previously overlooked in 2D conditions can have a significant impact in the natural habitat, and highlights the importance of considering the evolutionary selective pressures that have shaped the behavior, as well as the underlying genes and neural circuits.

Comparison of the Diagnostic Performance of Steatosis Indices for Discrimination of CT-Diagnosed Metabolic Dysfunction-Associated Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) was redefined as metabolic dysfunction-associated fatty liver disease (MAFLD) in 2020. Due to this, further validation of the non-invasive tests used in NAFLD diagnosis is required for MAFLD. There are five known steatosis indices for computed tomography (CT)-diagnosed MAFLD. These indices include the fatty liver index (FLI), the hepatic steatosis index (HSI), the lipid accumulation product (LAP), the visceral adiposity index (VAI), and the Zhejiang University index (ZJU). We aimed to analyze the diagnostic abilities of these five widely known steatosis indices for CT-diagnosed MAFLD. From March 2012 to October 2019, we retrospectively analyzed the clinical information and images of 1300 adults aged ≥19 years who underwent CT scans at our institution. To compare differences, the Chi-square test and independent t-test were used for categorical and continuous variables, respectively. The area under the receiver operating characteristic (AUROC) curve was used to validate the diagnostic accuracy of MAFLD. Of the five indices, FLI was the best at predicting MAFLD, with the highest AUROC (0.791). The sensitivity and specificity of FLI for diagnosing MAFLD were both 70.9%. The optimal cut-off value was 29.9. FLI is a useful surrogate index for screening MAFLD in clinical practice.

Anti-Obesity Effects of Traditional and Commercial Kochujang in Overweight and Obese Adults: A Randomized Controlled Trial.

Kochujang shows anti-obesity effects in cell and animal models. Kochujang is traditionally prepared via slow fermentation or commercially using Aspergillus oryzae. We analyze the anti-obesity effects of two types of Kochujang in overweight and obese adults. The analyses included the following groups: traditional Kochujang containing either a high-dose (HTK; n = 19), or a low-dose of beneficial microbes (LTK; n = 18), and commercial Kochujang (CK; n = 17). Waist circumference decreased significantly in the HTK and CK groups. Total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride levels decreased in the HTK and LTK groups. Visceral fat is significantly reduced in the HTK group. The population of beneficial microorganisms in stool samples increased in all groups. Consumption of Kochujang reduces visceral fat content and improves the lipid profile, which can be enhanced by enrichment with beneficial microbes. These results suggest that Kochujang has the potential for application in obesity prevention.

Evaluation of the Effectiveness of Fermented Soybean-Lettuce Powder for Improving Menopausal Symptoms.

Menopause syndrome causes a decline in the quality of life of postmenopausal women. Hormone therapy is recommended for the treatment of menopausal syndromes. However, it has several side effects. Soybean has been safely used to relieve the symptoms of menopause. Lettuce has antidiabetic and anti-inflammatory effects and improves sleep quality. Natural nitric oxide metabolites are produced through fermentation, which increases the effectiveness of the functional substances. This study assessed the alleviation of menopausal syndrome symptoms by natural nitric oxide-containing soybean lettuce extract using the Kupperman index. This study included adult women with menopausal syndrome and a Kupperman index of ≥15. After a four-week study with 40 participants, the final analysis included 39 participants in the experimental group (n = 19) and the placebo group (n = 20). Body mass index, waist circumference, and the total cholesterol, low-density and high-density lipoprotein cholesterol, and triglyceride levels were not altered before and after treatment in both groups. There was a significant decrease in the Kupperman index after treatment in the experimental group, but no significant change was observed in the placebo group. Soybean lettuce extract alleviates menopause syndrome without any special side effects.

Association of the Metabolic Dysfunction-Associated Fatty Liver Disease with Serum Uric Acid-to-Creatinine Ratio.

Background: No study has examined whether serum uric acid/creatinine (sUA/Cr) is associated with the newly defined metabolic-associated fatty liver disease (MAFLDs). Furthermore, studies on other factors influencing their relationship have not been conducted. Aim: To investigate the relationship between sUA/Cr and newly defined MAFLD, and to identify any factors that affect this relationship. Methods: We retrospectively reviewed the data of patients who underwent abdominal computed tomography (CT) at the Hospital Health Promotion Center. Participants were divided into the healthy (no evidence of liver disease; n = 707), MAFLD+non-heavy drinking (steatosis diagnosed by CT and drinking <140 and 70 grams/week for men and women, respectively; n = 291), and MAFLD+heavy drinking (fatty liver diagnosed by CT and drinking >140 and 70 grams/week for men and women, respectively; n = 61) groups. The relationship between sUA/Cr and MAFLD among the three groups were compared using multivariate logistic regression. Results: After adjusting for age, it was observed that when the sUA/Cr ratio increased by 1, the risk of MAFLD increased by 1.205 times the risk in the normal group. After adjusting for age, an increase by 1 in the sUA/Cr ratio increased the probability of non-heavy drinking+MAFLD and heavy drinking+MAFLD by 1.302 and 1.556 times, respectively, compared with healthy individuals. For those who smoked, the probability of heavy drinking+MAFLD was 9.901 times higher compared with healthy individuals. Conclusion: The newly defined MAFLD is related to sUA/Cr. The amount of alcohol consumption and smoking influenced the association between sUA/Cr and MAFLD.

Metabolic dysfunction associated fatty liver disease (MAFLD) and serum vitamin D concentration in South Korea.

BACKGROUND AND OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) has recently been renamed as metabolic dysfunction-associated fatty liver disease (MAFLD) by the Asian Pacific Association for the Study of the Liver (APASL) to reflect metabolic dysfunction. Vitamin D regulates free fatty acid flux from the periphery to the liver. The association MAFLD and vitamin D has been controversial. We investigated the association of MAFLD, nutrient intake, and vitamin D status in South Korean adults. METHODS AND STUDY DESIGN: We analyzed patient responses from the Korea National Health and Nutrition Examination survey (KNHANES) 2010-2011. The disease group was selected as per the latest guidelines. Steatosis was evaluated by the fatty liver index (FLI). Frequency analysis was performed on general characteristics. We compared differences in nutritional status using complex sample adjusted chi-square tests and generalized linear models. After adjusting for age, complex sample logistic regression analysis was used to examine the relationship between MAFLD and vitamin D. RESULTS: Aspartate aminotransferase (AST), alanine aminotransferase (ALT), LDL, triglyceride, creatinine, glucose, nutrient intake, and serum 25(OH)D concentrations were significantly elevated while HDL was reduced in the disease group than in the control group. The OR for 25(OH)D was 1.015 (95% CI: 1.004-1.026, p<0.0001). However, MAFLD presented no significant association with vitamin D concentration (OR 1.010, 95% CI: 0.985-1.037, p=0.431) after adjusting for age. CONCLUSIONS: We found no significant relationship between MAFLD and serum vitamin D concentration in South Korean adults.

Functional role of formate dehydrogenase 1 (FDH1) for host and nonhost disease resistance against bacterial pathogens.

Nonhost disease resistance is the most common type of plant defense mechanism against potential pathogens. In the present study, the metabolic enzyme formate dehydrogenase 1 (FDH1) was identified to associate with nonhost disease resistance in Nicotiana benthamiana and Arabidopsis thaliana. In Arabidopsis, AtFDH1 was highly upregulated in response to both host and nonhost bacterial pathogens. The Atfdh1 mutants were compromised in nonhost resistance, basal resistance, and gene-for-gene resistance. The expression patterns of salicylic acid (SA) and jasmonic acid (JA) marker genes after pathogen infections in Atfdh1 mutant indicated that both SA and JA are involved in the FDH1-mediated plant defense response to both host and nonhost bacterial pathogens. Previous studies reported that FDH1 localizes to mitochondria, or both mitochondria and chloroplasts. Our results showed that the AtFDH1 mainly localized to mitochondria, and the expression level of FDH1 was drastically increased upon infection with host or nonhost pathogens. Furthermore, we identified the potential co-localization of mitochondria expressing FDH1 with chloroplasts after the infection with nonhost pathogens in Arabidopsis. This finding suggests the possible role of FDH1 in mitochondria and chloroplasts during defense responses against bacterial pathogens in plants.

Overexpression of Arabidopsis nucleolar GTP-binding 1 (NOG1) proteins confers drought tolerance in rice.

As a major adverse environmental factor in most parts of the world, drought causes substantial crop yield losses. Rice (Oryza sativa) is one of the staple foods for more than one-half of the world's population. Rice plants are sensitive to even mild drought stress and need almost twice the amount of water compared to wheat (Triticum aestivum) or maize (Zea mays). Arabidopsis (Arabidopsis thaliana) small GTPase Nucleolar GTP-binding protein 1 (AtNOG1) plays a role in biotic stress tolerance. Here, we created transgenic rice lines constitutively overexpressing AtNOG1-1 or AtNOG1-2. We also developed rice RNA interference (RNAi) lines that show downregulation of OsNOG1. AtNOG1-1 and AtNOG1-2 overexpressors showed enhanced drought tolerance without compromising grain yield, whereas OsNOG1-RNAi was more susceptible to drought when compared to wild-type plants. Analysis of physiological parameters showed increased cell sap osmolality, relative water content, and abscisic acid (ABA) level, but decreased leaf water loss in AtNOG1-1 or AtNOG1-2 overexpressor lines compared to the control. We found upregulation of several genes involved in ABA and jasmonic acid (JA) signaling, stomata regulation, osmotic potential maintenance, stress protection, and disease resistance in AtNOG1-1 and AtNOG1-2 overexpressor lines compared to the control. We elucidated the role of NOG1-2 and NOG1-1 in regulation of silica body formation around stomata to prevent transpirational water loss. These results provide an avenue to confer drought tolerance in rice.

Differential release of extracellular vesicle tRNA from oxidative stressed renal cells and ischemic kidneys.

While urine-based liquid biopsy has expanded to the analyses of extracellular nucleic acids, the potential of transfer RNA (tRNA) encapsulated within extracellular vesicles has not been explored as a new class of urine biomarkers for kidney injury. Using rat kidney and mouse tubular cell injury models, we tested if extracellular vesicle-loaded tRNA and their m1A (N1-methyladenosine) modification reflect oxidative stress of kidney injury and determined the mechanism of tRNA packaging into extracellular vesicles. We determined a set of extracellular vesicle-loaded, isoaccepting tRNAs differentially released after ischemia-reperfusion injury and oxidative stress. Next, we found that m1A modification of extracellular vesicle tRNAs, despite an increase of the methylated tRNAs in intracellular vesicles, showed little or no change under oxidative stress. Mechanistically, oxidative stress decreases tRNA loading into intracellular vesicles while the tRNA-loaded vesicles are accumulated due to decreased release of the vesicles from the cell surface. Furthermore, Maf1-mediated transcriptional repression of the tRNAs decreases the cargo availability for extracellular vesicle release in response to oxidative stress. Taken together, our data support that release of extracellular vesicle tRNAs reflects oxidative stress of kidney tubules which might be useful to detect ischemic kidney injury and could lead to rebalance protein translation under oxidative stress.

Erratum: Interleukin-34 Limits the Therapeutic Effects of Immune Checkpoint Blockade.

[This corrects the article DOI: 10.1016/j.isci.2020.101584.].

Perceived Stress, Positive Resources and Their Interactions as Possible Related Factors for Depressive Symptoms.

OBJECTIVE: The present study aimed to explore how the patterns of interaction between stress and positive resources differ according to the severity of depression and which resources play the most important role among the various positive resources. METHODS: The study included 1,806 people who had visited a health screening center for a mental health check-up to evaluate the levels of perceived stress, positive resources, and depressive symptoms. The participants were divided into a depressive group (n=1,642, mean age 50.60, female 68%) and a non-depressive group (n=164, mean age 48.42, female 66.6%). We conducted hierarchical regression analyses and simple slope analyses to examine the interaction between perceived stress and positive resources. RESULTS: The interaction between perceived stress and optimism was significantly associated with depression in non-depressive groups. In depressive groups, the interactions between five types of positive resources (optimism, purpose in life, self-control, social support and care) and perceived stress were all significantly related to depression. CONCLUSION: Interventions that promote optimism can be helpful for preventing inevitable stress from leading to depression. A deficiency in positive resources may be a factor in aggravating depression in stressful situations for people reporting moderate to severe depressive symptoms.

A Novel Role of Salt- and Drought-Induced RING 1 Protein in Modulating Plant Defense Against Hemibiotrophic and Necrotrophic Pathogens.

Many plant-encoded E3 ligases are known to be involved in plant defense. Here, we report a novel role of E3 ligase SALT- AND DROUGHT-INDUCED RING FINGER1 (SDIR1) in plant immunity. Even though SDIR1 is reasonably well-characterized, its role in biotic stress response is not known. The silencing of SDIR1 in Nicotiana benthamiana reduced the multiplication of the virulent bacterial pathogen Pseudomonas syringae pv. tabaci. The Arabidopsis sdir1 mutant is resistant to virulent pathogens, whereas SDIR1 overexpression lines are susceptible to both host and nonhost hemibiotrophic bacterial pathogens. However, sdir1 mutant and SDIR1 overexpression lines showed hypersusceptibility and resistance, respectively, against the necrotrophic pathogen Erwinia carotovora. The mutant of SDIR1 target protein, i.e., SDIR-interacting protein 1 (SDIR1P1), also showed resistance to host and nonhost pathogens. In SDIR1 overexpression plants, transcripts of NAC transcription factors were less accumulated and the levels of jasmonic acid (JA) and abscisic acid were increased. In the sdir1 mutant, JA signaling genes JAZ7 and JAZ8 were downregulated. These data suggest that SDIR1 is a susceptibility factor and its activation or overexpression enhances disease caused by P. syringae pv. tomato DC3000 in Arabidopsis. Our results show a novel role of SDIR1 in modulating plant defense gene expression and plant immunity.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Antagonistic Regulation by CPN60A and CLPC1 of TRXL1 that Regulates MDH Activity Leading to Plant Disease Resistance and Thermotolerance.

Global warming and emerging plant diseases challenge agricultural food/feed production. We identify mechanism(s) regulating both plant thermotolerance and disease resistance. Using virus-induced gene silencing (VIGS)-based genetic screening, we identify a thioredoxin-like 1 (TRXL1) gene involved in plant nonhost disease resistance and thermotolerance. TRXL1 is reduced, partly degraded via proteases and proteasome, and alters its chloroplast localization during heat stress. TRXL1 interacts with more than 400 proteins, including chaperonin CPN60A, caseinolytic protease (CLPC1), and NADP-dependent malate dehydrogenase (NADP-MDH). Chaperonin 60A (CPN60A) guards TRXL1 from degradation, whereas CLPC1 degrades TRXL1 during heat stress. TRXL1 regulates NADP-MDH activity, leading to an increase in malate level and inhibition of superoxide radical formation. We show that CPN60A and NADP-MDH positively regulate nonhost resistance, and CPN60A positively and CLPC1 negatively regulate thermotolerance. This study shows an antagonistic post-translational regulation of TRXL1 by CPN60A and CLPC1 and regulation of MDH by TRXL1, leading to plant disease resistance and thermotolerance.

Interleukin-34 Limits the Therapeutic Effects of Immune Checkpoint Blockade.

Interleukin-34 (IL-34) is an alternative ligand to colony-stimulating factor-1 (CSF-1) for the CSF-1 receptor that acts as a key regulator of monocyte/macrophage lineage. In this study, we show that tumor-derived IL-34 mediates resistance to immune checkpoint blockade regardless of CSF-1 existence in various murine cancer models. Consistent with its immunosuppressive characteristics, the expression of IL-34 in tumors correlates with decreased frequencies of cellular (such as CD8+ and CD4+ T cells and M1-biased macrophages) and molecular (including various cytokines and chemokines) effectors at the tumor microenvironment. Then, a neutralizing antibody against IL-34 improved the therapeutic effects of the immune checkpoint blockade in combinatorial therapeutic models, including a patient-derived xenograft model. Collectively, we revealed that tumor-derived IL-34 inhibits the efficacy of immune checkpoint blockade and proposed the utility of IL-34 blockade as a new strategy for cancer therapy.

Iron-Sulfur Cluster Protein NITROGEN FIXATION S-LIKE1 and Its Interactor FRATAXIN Function in Plant Immunity.

Iron-sulfur (Fe-S) clusters are inorganic cofactors that are present in all kingdoms of life as part of a large number of proteins involved in several cellular processes, including DNA replication and metabolism. In this work, we demonstrate an additional role for two Fe-S cluster genes in biotic stress responses in plants. Eleven Fe-S cluster genes, including the NITROGEN FIXATION S-LIKE1 (NFS1) and its interactor FRATAXIN (FH), when silenced in Nicotiana benthamiana, compromised nonhost resistance to Pseudomonas syringae pv. tomato T1. NbNFS1 expression was induced by pathogens and salicylic acid. Arabidopsis (Arabidopsis thaliana) atnfs and atfh mutants, with reduced AtNFS1 or AtFH gene expression, respectively, showed increased susceptibility to both host and nonhost pathogen infection. Arabidopsis AtNFS1 and AtFH overexpressor lines displayed decreased susceptibility to infection by host pathogen P syringae pv. tomato DC3000. The AtNFS1 overexpression line exhibited constitutive upregulation of several defense-related genes and enrichment of gene ontology terms related to immunity and salicylic acid responses. Our results demonstrate that NFS1 and its interactor FH are involved not only in nonhost resistance but also in basal resistance, suggesting a new role of the Fe-S cluster pathway in plant immunity.

Ribosomal protein QM/RPL10 positively regulates defence and protein translation mechanisms during nonhost disease resistance.

Ribosomes play an integral part in plant growth, development, and defence responses. We report here the role of ribosomal protein large (RPL) subunit QM/RPL10 in nonhost disease resistance. The RPL10-silenced Nicotiana benthamiana plants showed compromised disease resistance against nonhost pathogen Pseudomonas syringae pv. tomato T1. The RNA-sequencing analysis revealed that many genes involved in defence and protein translation mechanisms were differentially affected due to silencing of NbRPL10. Arabidopsis AtRPL10 RNAi and rpl10 mutant lines showed compromised nonhost disease resistance to P. syringae pv. tomato T1 and P. syringae pv. tabaci. Overexpression of AtRPL10A in Arabidopsis resulted in reduced susceptibility against host pathogen P. syringae pv. tomato DC3000. RPL10 interacts with the RNA recognition motif protein and ribosomal proteins RPL30, RPL23, and RPS30 in the yeast two-hybrid assay. Silencing or mutants of genes encoding these RPL10-interacting proteins in N. benthamiana or Arabidopsis, respectively, also showed compromised disease resistance to nonhost pathogens. These results suggest that QM/RPL10 positively regulates the defence and translation-associated genes during nonhost pathogen infection.

PDX models of human lung squamous cell carcinoma: consideration of factors in preclinical and co-clinical applications.

BACKGROUND: Treatment of human lung squamous cell carcinoma (LUSC) using current targeted therapies is limited because of their diverse somatic mutations without any specific dominant driver mutations. These mutational diversities preventing the use of common targeted therapies or the combination of available therapeutic modalities would require a preclinical animal model of this tumor to acquire improved clinical responses. Patient-derived xenograft (PDX) models have been recognized as a potentially useful preclinical model for personalized precision medicine. However, whether the use of LUSC PDX models would be appropriate enough for clinical application is still controversial. METHODS: In the process of developing PDX models from Korean patients with LUSC, the authors investigated the factors influencing the successful initial engraftment of tumors in NOD scid gamma mice and the retainability of the pathological and genomic characteristics of the parental patient tumors in PDX tumors. CONCLUSIONS: The authors have developed 62 LUSC PDX models that retained the pathological and genomic features of parental patient tumors, which could be used in preclinical and co-clinical studies. Trial registration Tumor samples were obtained from 139 patients with LUSC between November 2014 and January 2019. All the patients provided signed informed consents. This study was approved by the institutional review board (IRB) of Samsung Medical Center (2018-03-110).