A non-canonical role for a small nucleolar RNA in ribosome biogenesis and senescence.

Cellular senescence is an irreversible state of cell-cycle arrest induced by various stresses, including aberrant oncogene activation, telomere shortening, and DNA damage. Through a genome-wide screen, we discovered a conserved small nucleolar RNA (snoRNA), SNORA13, that is required for multiple forms of senescence in human cells and mice. Although SNORA13 guides the pseudouridylation of a conserved nucleotide in the ribosomal decoding center, loss of this snoRNA minimally impacts translation. Instead, we found that SNORA13 negatively regulates ribosome biogenesis. Senescence-inducing stress perturbs ribosome biogenesis, resulting in the accumulation of free ribosomal proteins (RPs) that trigger p53 activation. SNORA13 interacts directly with RPL23, decreasing its incorporation into maturing 60S subunits and, consequently, increasing the pool of free RPs, thereby promoting p53-mediated senescence. Thus, SNORA13 regulates ribosome biogenesis and the p53 pathway through a non-canonical mechanism distinct from its role in guiding RNA modification. These findings expand our understanding of snoRNA functions and their roles in cellular signaling.

MTF1 genetic variants are associated with lung cancer risk in the Chinese Han population.

BACKGROUND: Metal-regulatory transcription factor 1 (MTF1), a conserved metal-binding transcription factor in eukaryotes, regulates the proliferation of cancer cells by activating downstream target genes and then participates in the formation and progression of tumors, including lung cancer (LC). The expression level of MTF1 is down-regulated in LC, and high expression of MTF1 is associated with a good prognosis of LC. However, the association between MTF1 polymorphism and LC risk has not been explored. METHODS: The genotyping of MTF1 Single nucleotide polymorphisms (SNPs) including rs473279, rs28411034, rs28411352, and rs3748682 was identified by the Agena MassARRAY system among 670 healthy controls and 670 patients with LC. The odds ratio (OR) and 95% confidence intervals (CI) were calculated by logistics regression to assess the association of these SNPs with LC risk. RESULTS: MTF1 rs28411034 (OR 1.22, 95% CI 1.03-1.45, p = 0.024) and rs3748682 (OR 1.24, 95% CI 1.04-1.47, p = 0.014) were associated with higher LC susceptibility overall. Moreover, the effect of rs28411034 and rs3748682 on LC susceptibility was observed in males, subjects with body mass index (BMI) ≥ 24 kg/m2, smokers, drinkers, and patients with lung squamous carcinoma (OR and 95% CI > 1, p < 0.05). Besides, rs28411352 (OR 0.73, 95% CI 0.55-0.97, p = 0.028,) showed protective effect for reduced LC risk in drinkers. CONCLUSIONS: We were first who reported that rs28411034 and rs3748682 tended to be relevant to increased LC susceptibility among the Chinese Han population. These results of this study could help to recognize the pathogenic mechanisms of the MTF1 gene in LC progress.

Multiple machine-learning tools identifying prognostic biomarkers for acute Myeloid Leukemia.

BACKGROUND: Acute Myeloid Leukemia (AML) generally has a relatively low survival rate after treatment. There is an urgent need to find new biomarkers that may improve the survival prognosis of patients. Machine-learning tools are more and more widely used in the screening of biomarkers. METHODS: Least Absolute Shrinkage and Selection Operator (LASSO), Support Vector Machine-Recursive Feature Elimination (SVM-RFE), Random Forest (RF), eXtreme Gradient Boosting (XGBoost), lrFuncs, IdaProfile, caretFuncs, and nbFuncs models were used to screen key genes closely associated with AML. Then, based on the Cancer Genome Atlas (TCGA), pan-cancer analysis was performed to determine the correlation between important genes and AML or other cancers. Finally, the diagnostic value of important genes for AML was verified in different data sets. RESULTS: The survival analysis results of the training set showed 26 genes with survival differences. After the intersection of the results of each machine learning method, DNM1, MEIS1, and SUSD3 were selected as key genes for subsequent analysis. The results of the pan-cancer analysis showed that MEIS1 and DNM1 were significantly highly expressed in AML; MEIS1 and SUSD3 are potential risk factors for the prognosis of AML, and DNM1 is a potential protective factor. Three key genes were significantly associated with AML immune subtypes and multiple immune checkpoints in AML. The results of the verification analysis show that DNM1, MEIS1, and SUSD3 have potential diagnostic value for AML. CONCLUSION: Multiple machine learning methods identified DNM1, MEIS1, and SUSD3 can be regarded as prognostic biomarkers for AML.

Insights into Stereoselectivity Switch in Michael Addition-Initiated Tandem Mannich Cyclizations and Their Extension from Enamines to Vinyl Ethers.

Both cis- and trans- tetracyclic spiroindolines are the core of many important biologically active indole alkaloids, but the divergent synthesis of these important motifs is largely hampered by the limited stereoselectivity control. A facile stereoinversion protocol is reported here in Michael addition-initiated tandem Mannich cyclizations for constructing tetracyclic spiroindolines, providing an easy access to two diastereoisomeric cores of monoterpene indole alkaloids with high selectivity. The mechanistic studies including in situ NMR experiments, control experiments, and DFT calculations reveal that the reaction undergoes a unique retro-Mannich/re-Mannich rearrangement including a C-C bond cleavage that is very rare for a saturated six-membered carbocycle. Insights into the stereoinversion process have been uncovered, and the major effects were determined to be the electronic properties of N-protecting groups of the indole with the aid of Lewis acid catalysts. By understanding these insights, the stereoselectivity switching strategy is also smoothly applied from enamine substrates to vinyl ether substrates, which are enriched greatly for the divergent synthesis and stereocontrol of monoterpene indole alkaloids. The current reaction also proves to be very practical and was successfully applied to the gram-scale total synthesis of strychnine and deethylibophyllidine in short routes.

Prognostic implication of serum glycated albumin for patients with non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention.

BACKGROUND: It has been demonstrated that glycated albumin (GA) is significantly associated with diabetes complications and mortality. However, among patients diagnosed with non-ST-elevation acute coronary syndrome (NSTE-ACS) administered percutaneous coronary intervention (PCI), the predictive value of GA for poor prognosis is unclear. METHODS: This study eventually included 2247 NSTE-ACS patients in Beijing Anzhen Hospital, Capital Medical University in January-December 2015 who received PCI. All patients were followed up until death or for 48 months post-discharge. The primary endpoint was major adverse cardio-cerebral events (MACCEs), including all-cause death, non-fatal myocardial infarction, ischemia-induced revascularization and non-fatal ischemic stroke. RESULTS: In total, 547 (24.3%) MACCEs were recorded during the follow-up period. Upon adjusting for potential confounders, GA remained an important risk predictor of MACCEs (As nominal variate: hazard ratio [HR] 1.527, 95% confidence interval [CI] 1.236-1.886, P < 0.001; As continuous variate: HR 1.053, 95% CI 1.027-1.079, P < 0.001). GA addition significantly enhanced the predictive ability of the traditional risk model (Harrell's C-index, GA vs. Baseline model, 0.694 vs. 0.684, comparison P = 0.002; continuous net reclassification improvement (continuous-NRI) 0.085, P = 0.053; integrated discrimination improvement (IDI) 0.007, P = 0.020). CONCLUSION: GA is highly correlated with poor prognosis in NSTE-ACS patients undergoing PCI, suggesting that it may be a major predictive factor of adverse events among these individuals.

Association of CYP19A1 rs28757157 polymorphism with lung cancer risk in the Chinese Han population.

BACKGROUND: Lung cancer is the leading cause of cancer death globally. Recent studies have revealed that CYP19A1 gene plays a crucial role in cancer initiation and development. The aim of this study was to assess the association of CYP19A1 genetic polymorphisms with the risk of lung cancer in the Chinese Han population. METHODS: This study randomly recruited 489 lung cancer patients and 467 healthy controls. The genotypes of four single nucleotide polymorphisms (SNPs) of the CYP19A1 gene were identified by the Agena MassARRY technique. Genetic model analysis was used to assess the association between genetic variations and lung cancer risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the effect of four selected SNPs on lung cancer risk. RESULTS: CYP19A1 rs28757157 might contribute to an increased risk of lung cancer (p = 0.025, OR = 1.30, 95% CI 1.03-1.64). In stratified analysis, rs28757157 was associated with an increased cancer risk in the population aged under 60 years, females, smokers, and drinkers. Besides, rs3751592 and rs59429575 were also identified as risk biomarkers in the population under 60 years and drinkers. Meanwhile, a relationship between an enhanced risk of squamous cell carcinoma and rs28757157 was found, while the rs3751592 CC genotype was identified as a risk factor for lung adenocarcinoma development. CONCLUSIONS: This study has identified revealed that the three SNPs (rs28757157, rs3751592, and rs59429575) of CYP19A1 are associated with lung cancer in the Chinese Han population. These findings will provide theoretical support for further functional studies of CYP19A1 in lung cancer.

Comparison of various insulin resistance surrogates on prognostic prediction and stratification following percutaneous coronary intervention in patients with and without type 2 diabetes mellitus.

BACKGROUND: Insulin resistance (IR), evaluation of which is difficult and complex, is closely associated with cardiovascular disease. Recently, various IR surrogates have been proposed and proved to be highly correlated with IR assessed by the gold standard. It remains indistinct whether different IR surrogates perform equivalently on prognostic prediction and stratification following percutaneous coronary intervention (PCI) in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients with and without type 2 diabetes mellitus (T2DM). METHODS: The present study recruited patients who were diagnosed with NSTE-ACS and successfully underwent PCI. IR surrogates evaluated in the current study included triglyceride-glucose (TyG) index, visceral adiposity index, Chinese visceral adiposity index, lipid accumulation product, and triglyceride-to-high density lipoprotein cholesterol ratio, calculations of which were conformed to previous studies. The observational endpoint was defined as the major adverse cardiovascular and cerebrovascular events (MACCE), including cardiac death, non-fatal myocardial infarction, and non-fatal ischemic stroke. RESULTS: 2107 patients (60.02 ± 9.03 years, 28.0% female) were ultimately enrolled in the present study. A total of 187 (8.9%) MACCEs were documented during the 24-month follow-up. Despite regarding the lower median as reference [hazard ratio (HR) 3.805, 95% confidence interval (CI) 2.581-5.608, P < 0.001] or evaluating 1 normalized unit increase (HR 1.847, 95% CI 1.564-2.181, P < 0.001), the TyG index remained the strongest risk predictor for MACCE, independent of confounding factors. The TyG index showed the most powerful diagnostic value for MACCE with the highest area under the receiver operating characteristic curve of 0.715. The addition of the TyG index, compared with other IR surrogates, exhibited the maximum enhancement on risk stratification for MACCE on the basis of a baseline model (Harrell's C-index: 0.708 for baseline model vs. 0.758 for baseline model + TyG index, P < 0.001; continuous net reclassification improvement: 0.255, P < 0.001; integrated discrimination improvement: 0.033, P < 0.001). The results were consistent in subgroup analysis where similar analyses were performed in patients with and without T2DM, respectively. CONCLUSION: The TyG index, which is most strongly associated with the risk of MACCE, can be served as the most valuable IR surrogate for risk prediction and stratification in NSTE-ACS patients receiving PCI, with and without T2DM.

Triglyceride glucose index for predicting cardiovascular outcomes after percutaneous coronary intervention in patients with type 2 diabetes mellitus and acute coronary syndrome.

BACKGROUND: The triglyceride glucose (TyG) index, a simple surrogate estimate of insulin resistance, has been demonstrated to predict cardiovascular (CV) disease morbidity and mortality in the general population and many patient cohorts. However, to our knowledge, the prognostic usefulness of the TyG index after percutaneous coronary intervention (PCI) in patients with type 2 diabetes mellitus (T2DM) and acute coronary syndrome (ACS) has not been determined. This study aimed to evaluate the association of the TyG index with adverse CV outcomes in patients with T2DM and ACS who underwent PCI. METHODS: The TyG index was calculated using the formula ln[fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. The primary endpoint was the composite of all-cause mortality, non-fatal stroke, non-fatal myocardial infarction, or unplanned repeat revascularization. The association between the TyG index and adverse CV outcomes was assessed by Cox proportional hazards regression analysis. RESULTS: In total, 776 patients with T2DM and ACS who underwent PCI (mean age, 61 ± 10 years; men, 72.2%) were included in the final analysis. Over a median follow-up of 30 months, 188 patients (24.2%) had at least 1 primary endpoint event. The follow-up incidence of the primary endpoint rose with increasing TyG index tertiles. The multivariate Cox proportional hazards regression analysis adjusted for multiple confounders revealed a hazard ratio for the primary endpoint of 2.17 (95% CI 1.45-3.24; P for trend = 0.001) when the highest and lowest TyG index tertiles were compared. CONCLUSIONS: The TyG index was significantly and positively associated with adverse CV outcomes, suggesting that the TyG index may be a valuable predictor of adverse CV outcomes after PCI in patients with T2DM and ACS.

Impacts of triglyceride-glucose index on prognosis of patients with type 2 diabetes mellitus and non-ST-segment elevation acute coronary syndrome: results from an observational cohort study in China.

BACKGROUND: The relationship between triglyceride-glucose index (TyG index) and the prevalence and prognosis of cardiovascular disease has been confirmed by former studies. However, it remains uncertain whether TyG index has a prognostic impact in patients with type 2 diabetes mellitus (T2DM) and non-ST-segment elevation acute coronary syndrome (NSTE-ACS) undergoing percutaneous coronary intervention (PCI). METHODS: The study retrospectively enrolled 798 patients (mean age: 60.9 ± 8.3 years; 68.3% men) with T2DM and NSTE-ACS who underwent PCI at Beijing Anzhen Hospital from January to December 2015. TyG index was calculated as previously reported: ln [fasting TGs (mg/dL) * FBG (mg/dL)/2]. The primary endpoint was a composite of adverse events as follows: all-cause death, non-fatal myocardial infarction (MI) and ischemia-driven revascularization. RESULTS: TyG index was significantly higher in patients with a primary endpoint event compared with those without. Multivariate Cox proportional hazards analysis showed that 1-unit increase of TyG index was independently associated with higher risk of primary endpoint, independent of other risk factors [hazard ratio (HR) 3.208 per 1-unit increase, 95% confidence interval (CI) 2.400-4.289, P < 0.001]. The addition of TyG index to a baseline risk model had an incremental effect on the predictive value for adverse prognosis [AUC: baseline risk model, 0.800 vs. baseline risk model + TyG index, 0.856, P for comparison < 0.001; category-free net reclassification improvement (NRI) 0.346, P < 0.001; integrated discrimination improvement (IDI) 0.087, P < 0.001]. CONCLUSIONS: Increased TyG index is a significant predictor of adverse prognosis in patients with T2DM and NSTE-ACS undergoing PCI. Further studies need to be performed to determine whether interventions for TyG index have a positive impact on improving clinical prognosis.

Impacts of geriatric nutritional risk index on prognosis of patients with non-ST-segment elevation acute coronary syndrome: Results from an observational cohort study in China.

BACKGROUND AND AIMS: It is recognized that malnutrition increases risk of worse prognosis in patients with various diseases. The present study investigated if poor nutritional status predicts adverse outcomes in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: The study enrolled 2299 patients (mean age: 60.01 ± 8.95 years; 71.8% male) with NSTE-ACS who underwent PCI at Beijing Anzhen Hospital from January to December 2015. The entire cohort was divided into training set (n = 1519) and testing set (n = 780) at a ratio of approximate 2 : 1. Nutritional status was assessed by geriatric nutritional risk index (GNRI). The primary endpoint was a composite of adverse events as follows: all-cause death, non-fatal myocardial infarction (MI) and any revascularization. Multivariate Cox analysis showed that GNRI significantly associated with primary endpoint, independent of other risk factors [hazard ratio (HR) 1.159 per 1-point decrease of GNRI, 95% confidence interval (CI) 1.130-1.189, p < 0.001]. The addition of GNRI to a baseline model had an incremental effect on the predictive value for adverse prognosis in training set [AUC: from 0.821 to 0.873, p < 0.001; category-free net reclassification improvement (NRI): 0.313, p < 0.001; integrated discrimination improvement (IDI): 0.108, p < 0.001]. The incremental effect of GNRI was further validated and confirmed in testing set. CONCLUSION: Lower GNRI is a significant predictor of adverse prognosis in patients with NSTE-ACS undergoing PCI. Further studies need to be performed to determine whether nutritional interventions have a positive impact on improving clinical prognosis.

Prognostic impact of estimated remnant-like particle cholesterol in patients with differing glycometabolic status: an observational cohort study from China.

BACKGROUND: It is uncertain whether estimated remnant-like particle cholesterol (RLP-C) could predict residual risk in patients with different glycometabolic status. This study aimed to evaluate the relationship between estimated RLP-C and adverse prognosis in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) treated with percutaneous coronary intervention (PCI) and to identify the potential impact of glycometabolism on the predictive value of estimated RLP-C. METHODS: The study assessed 2419 participants with NSTE-ACS undergoing PCI at Beijing Anzhen Hospital from January to December 2015. Estimated RLP-C was calculated as follows: total cholesterol (TC) minus low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). The adverse events included all-cause death, non-fatal myocardial infarction (MI), and ischemia-driven revascularization. RESULTS: Estimated RLP-C was prominently associated with adverse prognosis in the total population [hazard ratio (HR) 1.291 per 1-SD increase, 95% confidence interval (CI) 1.119-1.490, P <  0.001], independent of confounding risk factors. However, subgroup analysis showed that increasing estimated RLP-C was related to a higher risk of adverse events in the diabetic population only [HR 1.385 per 1-SD increase, 95% CI 1.183-1.620, P <  0.001]. Estimated RLP-C failed to be a significant determinant of adverse prognosis in non-diabetic and pre-diabetic subgroups. The addition of estimated RLP-C to a baseline model including traditional risk factors enhanced the predictive performance both in total and diabetic populations. CONCLUSIONS: High estimated RLP-C level is a significant predictor for recurrent adverse events in patients with diabetes and NSTE-ACS treated with PCI.

Prognostic impact of the atherogenic index of plasma in type 2 diabetes mellitus patients with acute coronary syndrome undergoing percutaneous coronary intervention.

BACKGROUND: The association of the atherogenic index of plasma (AIP), an emerging lipid index that can predict the risk for cardiovascular disease, with adverse outcomes in type 2 diabetes mellitus (T2DM) patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) has not been determined. Therefore, the aim of this study was to investigate whether the AIP could independently predict adverse cardiovascular events in T2DM patients with ACS undergoing PCI. METHODS: This study was a retrospective analysis of a single-centre prospective registry involving 826 consecutive T2DM patients who underwent primary or elective PCI for ACS from June 2016 to November 2017. This study ultimately included 798 patients (age, 61 ± 10 years; male, 72.7%). The AIP was calculated as the base 10 logarithm of the ratio of the plasma concentration of triglycerides to high-density lipoprotein-cholesterol (HDL-C). All the patients were divided into 4 groups based on the AIP quartiles. The primary endpoint was a composite of death from any cause, non-fatal spontaneous myocardial infarction (MI), non-fatal ischaemic stroke, and unplanned repeat revascularization. The key secondary endpoint was a composite of cardiovascular death, non-fatal MI, and non-fatal ischaemic stroke. RESULTS: During a median follow-up period of 927 days, 198 patients developed at least one event. An unadjusted Kaplan-Meier analysis showed that the incidence of the primary endpoint increased gradually with rising AIP quartiles (log-rank test, P = 0.001). A multivariate Cox proportional hazards analysis revealed that compared with the lowest AIP quartile, the top AIP quartile was associated with significantly increased risk for the primary and key secondary endpoints (hazard ratio [HR]: 2.249, 95% confidence interval [CI]: 1.438 to 3.517, P < 0.001; and HR: 2.571, 95% CI: 1.027 to 6.440, P = 0.044, respectively). CONCLUSIONS: A higher AIP value on admission was independently and strongly associated with adverse cardiovascular events in T2DM patients with ACS undergoing PCI.

Biological and Chemical Diversity of Marine Sponge-Derived Microorganisms over the Last Two Decades from 1998 to 2017.

Marine sponges are well known as rich sources of biologically natural products. Growing evidence indicates that sponges harbor a wealth of microorganisms in their bodies, which are likely to be the true producers of bioactive secondary metabolites. In order to promote the study of natural product chemistry and explore the relationship between microorganisms and their sponge hosts, in this review, we give a comprehensive overview of the structures, sources, and activities of the 774 new marine natural products from sponge-derived microorganisms described over the last two decades from 1998 to 2017.

TNIP1 Polymorphisms with the Risk of Hepatocellular Carcinoma Based on Chronic Hepatitis B Infection in Chinese Han Population.

Chronic hepatitis B virus (HBV) infection is an important etiology for the development of hepatocellular carcinoma (HCC). Tumor necrosis factor-α-induced protein 3-interacting protein 1 (TNIP1) is linked to specific inflammatory diseases as a novel type of endogenous inflammatory regulator. However, presently, rare information is found about the association between TNIP1 polymorphisms and HBV-induced HCC risk. In this case control study, we genotyped four single nucleotide polymorphisms (SNPs) in TNIP1 gene in 248 HCC patients and 242 chronic HBV carriers using Sequenom Mass-ARRAY technology. Genetic model and haplotype analysis were performed to evaluate the association between candidate SNPs polymorphisms and HBV-induced HCC susceptibility using Pearson's χ2 test and unconditional logistic regression analysis. Overall, we found two risk alleles in TNIP1 for HBV-induced HCC in patients: the allele "G" of rs7708392 by genotype model ("G/C" vs. "C/C": OR 1.88, 95% CI 1.17-3, P = 0.009) and dominant model ("G/C-G/G" vs. "C/C": OR 1.69, 95% CI 1.08-2.65, P = 0.023), and the allele "C" of rs10036748 by genotype model ("C/T" vs. "T/T": OR 1.83, 95% CI 1.14-2.92, P = 0.012) and dominant model ("C/T-C/C" vs. "T/T": OR 1.65, 95% CI 1.05-2.59, P = 0.03). However, rs3792792 and rs4958881 polymorphisms didn't significantly correlate with the risk of HBV-induced HCC. Haplotype analysis showed no significant association between haplotypes and the HCC risk in HBV carriers. This study provides evidence for HBV-induced HCC susceptibility gene TNIP1 in the Chinese Han population.

Combined linkage and association mapping reveal candidate loci for kernel size and weight in maize.

Yield improvement is a top priority for maize breeding. Kernel size and weight are important determinants of maize grain yield. In this study, a recombinant inbred line (RIL) population and an association panel were used to identify quantitative trait loci (QTLs) for four maize kernel-related traits: kernel length, width, thickness and 100-kernel weight. Twenty-seven QTLs were identified for kernel-related traits across three environments and the best linear unbiased predictions (BLUPs) of each trait by linkage analysis, and four QTLs were stably detected in more than two environments. Additionally, 29 single nucleotide polymorphisms (SNPs) were identified as significantly associated with the four kernel-related traits and BLUPs by genome-wide association study, and two loci could be stably detected in both environments. In total, four QTLs/SNPs were co-associated with various traits in both populations. Using combined-linkage analysis and association mapping, PZE-101066560 on chromosome 1, associated with kernel width and with 100-kernel weight in the association panel, was co-localized within the QTL interval of qKW1-3 for kernel width in the RILs. Two annotated genes in the candidate region were considered as potential candidate genes. The QTLs and candidate genes identified here will facilitate molecular breeding for grain yield improvement in maize.

Highly Efficient Formal [2+2+2] Strategy for the Rapid Construction of Polycyclic Spiroindolines: A Concise Synthesis of 11-Demethoxy-16-epi-myrtoidine.

A novel formal [2+2+2] strategy for the stereoselective elaboration of polycyclic indole alkaloids is described. Upon treatment with the catalyst InCl3 (5 mol %), tryptamine-derived enamides reacted readily with methylene malonate, thus enabling rapid and gram-scale access to versatile tetracyclic spiroindolines with excellent diastereoselectivity (21 examples, up to 95 % yield, up to d.r.>95:5). This strategy provides a concise approach to alkaloids isolated from Strychnos myrtoides, as demonstrated by a short synthesis of 11-demethoxy-16-epi-myrtoidine.

Identification of Single Nucleotide Polymorphic Loci and Candidate Genes for Seed Germination Percentage in Okra under Salt and No-Salt Stresses by Genome-Wide Association Study.

Excessive soil salinity is a major stressor inhibiting crops' growth, development, and yield. Seed germination is a critical stage of crop growth and development, as well as one of the most salt-sensitive stages. Salt stress has a significant inhibitory effect on seed germination. Okra is a nutritious vegetable, but its seed germination percentage (GP) is low, whether under salt stress conditions or suitable conditions. In this study, we used 180 okra accessions and conducted a genome-wide association study (GWAS) on the germination percentage using 20,133,859 single nucleotide polymorphic (SNP) markers under 0 (CK, diluted water), 70 (treatment 1, T1), and 140 mmol/L (treatment 2, T2) NaCl conditions. Using the mixed linear model (MLM) in Efficient Mixed-model Association eXpedated (EMMAX) and Genome-wide Efficient Mixed Model Association (GEMMA) software, 511 SNP loci were significantly associated during germination, of which 167 SNP loci were detected simultaneously by both programs. Among the 167 SNPs, SNP2619493 on chromosome 59 and SNP2692266 on chromosome 44 were detected simultaneously under the CK, T1, and T2 conditions, and were key SNP loci regulating the GP of okra seeds. Linkage disequilibrium block analysis revealed that nsSNP2626294 (C/T) in Ae59G004900 was near SNP2619493, and the amino acid changes caused by nsSNP2626294 led to an increase in the phenotypic values in some okra accessions. There was an nsSNP2688406 (A/G) in Ae44G005470 near SNP2692266, and the amino acid change caused by nsSNP2688406 led to a decrease in phenotypic values in some okra accessions. These results indicate that Ae59G004900 and Ae44G005470 regulate the GP of okra seeds under salt and no-salt stresses. The gene expression analysis further demonstrated these results. The SNP markers and genes that were identified in this study will provide reference for further research on the GP of okra, as well as new genetic markers and candidate genes for cultivating new okra varieties with high GPs under salt and no-salt stress conditions.

The role of the Gas6/TAM signal pathway in the LPS-induced pulmonary epithelial cells injury.

BACKGROUND: Acute lung injury (ALI) is an acute inflammatory respiratory disease. The interaction between growth arrest-specific 6 (Gas6) and tyrosine kinases of the Tyro3, Axl, Mer (TAM) family plays an important role in a variety of physiological and pathological processes, including inflammation. In this study, we mainly clarified the mechanism of the Gas6/TAM signal pathway in lipopolysaccharide (LPS)-induced pulmonary epithelial cells (BEAS-2B cells) injury. METHODS: We cultured BEAS-2B cells in vitro and established a LPS-induced BEAS-2B cells injury model. Then, the siRNA sequence (siGas6-2) was transfected into cells. The expression of Gas6/TAM was measured based on quantitative reverse transcription polymerase chain reaction (qRT-RCR) and western blot (WB). Cell proliferation and apoptosis were measured by cell counting Kit-8 (CCK-8) and flow cytometry. The expression of pro-inflammatory factors was measured by qRT-RCR and WB. RESULTS: Our study showed that when the 40 µg/mL LPS-induced BEAS-2B cells injury model was established, cell viability was significantly reduced, but the Gas6/TAM signal pathway was activated. When transfection with siGas6-2, low expression of Gas6 directly reduced the expression of downstream TAM receptors. Furthermore, the inhibition of the Gas6/TAM signal pathway significantly reduced the occurrence of cell apoptosis and the expression of inflammatory factors, and promoted cell proliferation. CONCLUSION: Our research indicated that Gas6/TAM played an important role in cell proliferation, apoptosis, and inflammatory response in the LPS-induced BEAS-2B cells injury, and Gas6/TAM may be a new target in the treatment of ALI in the future.

Pan-cancer analysis of the PDE4DIP gene with potential prognostic and immunotherapeutic values in multiple cancers including acute myeloid leukemia.

Phosphodiesterase 4D interacting protein (PDE4DIP) interacts with cAMP-specific phosphodiesterase 4D and its abnormal expression promotes the development of hematological malignancies, breast cancer, and pineal cell carcinoma. However, there is currently no systematic pan-cancer analysis of the association between PDE4DIP and various cancers. Thus, this study aimed to elucidate the potential functions of PDE4DIP in various cancers. Based on the multiple public databases and online websites, we conducted comprehensive analyses for PDE4DIP in various cancers, including differential expression, prognosis, genetic variation, DNA methylation, and immunity. We thoroughly analyzed the specific role of PDE4DIP in acute myeloid leukemia (LAML). The results indicated that there were differences in PDE4DIP expression in cancers, and in kidney chromophobe, LAML, pheochromocytoma and paraganglioma, thymoma, and uveal melanoma, PDE4DIP had potential prognostic value. PDE4DIP expression was also correlated with genetic variation, DNA methylation, immune cell infiltration, and immune-related genes in cancers. Functional enrichment analysis showed that PDE4DIP was mainly related to immune-related pathways in cancers, and in LAML, PDE4DIP was mainly related to immunoglobulin complexes, T-cell receptor complexes, and immune response regulatory signaling pathways. Our study systematically revealed for the first time the potential prognostic and immunotherapeutic value of PDE4DIP in various cancers, including LAML.

IL1RL1 polymorphisms rs12479210 and rs1420101 are associated with increased lung cancer risk in the Chinese Han population.

Background: Lung cancer is one of the most common human malignant diseases. In this study, we aimed to explore the association between IL1RL1 genetic polymorphisms and lung cancer risk in the Chinese Han population. Methods: We selected and genotyped six SNPs in the IL1RL1 gene using the Agena MassARRAY system in 507 lung cancer patients and 507 healthy controls. The association between IL1RL1 variants and lung cancer risk was assessed using logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Multi-factor dimensionality reduction (MDR) was used to analyze the impact of SNP-SNP interactions on the risk of lung cancer. Results: The results of overall analysis indicated that rs12479210 (T vs. C: OR = 1.42, FDR-p = 0.002; TC vs. CC: OR = 1.70, FDR-p < 0.0001; TT vs. CC: OR = 1.77, FDR-p = 0.032; TT-TC vs. CC: OR = 1.71, FDR-p = 0.001; additive: OR = 1.44, FDR-p = 0.001) and rs1420101 (T vs. C: OR = 1.31, FDR-p = 0.036; TT-TC vs. CC: OR = 1.42, FDR-p = 0.031; additive: OR = 1.30, FDR-p = 0.030) were associated with an increased the risk of lung cancer among the Chinese Han population. Stratified analysis also found the association between these two SNPs and lung cancer risk. However, there were no significant association observed between the other four SNPs (rs3771180, rs3771175, rs10208293, and rs10197862) in IL1RL1 and lung cancer risk. Furthermore, MDR analysis showed that rs12479210 was the best single model with the highest testing accuracy (0.566) and perfect CVC (10/10) for predicting lung cancer risk. The expression level of the IL1RL1 gene is lower in lung cancer tissue than normal tissue, and there are significant differences in the expression levels of IL1RL1 between rs12479210 and rs1420101 genetypes in lung cancer tissue (p < 0.05). Conclusion: Our findings suggest that IL1RL1 genetic variants (rs12479210 and rs1420101) are associated with an increased lung cancer risk in the Chinese Han population. These risk variants may serve as biomarkers for the prevention and treatment of lung cancer.