Genome-wide analysis of maize PR-1 gene family and expression profiles induced by plant hormones and fungal phytopathogens.

OBJECTIVE: In order to find similarity of the protein X in maize with other species we performed a BLASTP search to identify the maize ZmPR-1 family genes. METHODS: We used a BLASTP search to identify the maize ZmPR-1 family genes that may show similarities between the protein X in maize and other species. RESULTS: A total of 17 ZmPR-1 genes were identified and these genes were unevenly distributed on 8 chromosomes of maize. All ZmPR-1 gene predicted proteins contained a conserved CAP domain, according to the results of multiple sequence alignment and gene structure analysis. Phylogenetic tree analysis of a total of 85 PR-1 protein sequences from maize, sorghum, rice and Arabidopsis showed that the PR-1 family proteins were divided into four categories, and the maize ZmPR-1 was closely related to sorghum PR-1. In the promoter of maize ZmPR-1 gene, hypothetical cis-elements related to fungal induction, defense stress response, plant hormones, low temperature and drought response were detected. Microarray data analysis showed that ZmPR-1 displayed a tissue-specific expression pattern at different developmental stages, and responded to the infections of five maize pathogens. In addition, we further verified that four ZmPR-1 genes (ZmPR-1-5, 12, 14 and 16) were not only significantly up-regulated after Setosphearia turcica infection, but also affected by exogenous cues such as SA, ABA, MeJA and H2O2. CONCLUSION: The ZmPR-1 family may be important in plant disease resistance. This study's data provide important clues for future research on the function of ZmPR-1 family genes.

Treatment effect of metformin combined with atorvastatin in reducing in-stent restenosis after percutaneous coronary intervention in coronary artery disease patients with type 2 diabetic patients.

To investigate the effectiveness of metformin and atorvastatin in preventing in-stent restenosis (ISR) on coronary patients with type 2 diabetes mellitus with percutaneous coronary intervention within 8 to 12 months after rapamycin-eluting stent implantation. A total of 1278 consecutive patients implanted with rapamycin-eluting stent from January 2012 to December 2019, who underwent coronary computed tomography or coronary angiography within 8 to 12 months. The patients were categorized into atorvastatin 20 mg, or atorvastatin 20 mg + metformin 1.5/d, or atorvastatin 40 mg + metformin 1.5/d groups. The clinical characteristics of the 3 groups were compared. The correlation between variables and ISR was analyzed. A total of 701 patients participated in the study. The ratio of ISR/nonstenosis (P = .039) and fasting blood sugar (P = .001) differed significantly in the 3 groups. Logistic regression showed that d, L, different therapeutic agents, and dosage groups were independent risk factors of ISR. The longer L and smaller d may increase ISR incidence with 8 to 12 months after percutaneous coronary intervention. Both metformin and atorvastatin are beneficial in reducing stent restenosis by a dose-dependent manner. An increasing dose of atorvastatin and a combination of metformin decreases the incidence of ISR in patients.

Genome-wide analysis of Dof transcription factors and their response to cold stress in rice (Oryza sativa L.).

BACKGROUND: Rice (Oryza sativa L.) is a food crop for humans worldwide. However, temperature has an effect during the vegetative and reproductive stages. In high-latitude regions where rice is cultivated, cold stress is a major cause of yield loss and plant death. Research has identified a group of plant-specific transcription factors, DNA binding with one zinc fingers (DOFs), with a diverse range of functions, including stress signaling and stress response during plant growth. The aim of this study was to identify Dof genes in two rice subspecies, indica and japonica, and screen for Dof genes that may be involved in cold tolerance during plant growth. RESULTS: A total of 30 rice Dofs (OsDofs) were identified using bioinformatics and genome-wide analyses and phylogenetically analyzed. The 30 OsDOFs were classified into six subfamilies, and 24 motifs were identified based on protein sequence alignment. The chromosome locations of OsDofs were determined and nine gene duplication events were identified. A joint phylogenetic analysis was performed on DOF protein sequences obtained from four monocotyledon species to examine the evolutionary relationship of DOF proteins. Expression profiling of OsDofs from two japonica cultivars (Longdao5, which is cold-tolerant, and Longjing11, which is cold-sensitive) revealed that OsDof1 and OsDof19 are cold-inducible genes. We examined the seed setting rates in OsDof1- and OsDof19-overexpression and RNAi lines and found that OsDof1 showed a response to cold stress. CONCLUSIONS: Our investigation identified OsDof1 as a potential target for genetic breeding of rice with enhanced cold tolerance.

Low-Density Lipoprotein Cholesterol 4: The Notable Risk Factor of Coronary Artery Disease Development.

Background: Coronary artery disease (CAD) is the leading cause of death worldwide, which has a long asymptomatic period of atherosclerosis. Thus, it is crucial to develop efficient strategies or biomarkers to assess the risk of CAD in asymptomatic individuals. Methods: A total of 356 consecutive CAD patients and 164 non-CAD controls diagnosed using coronary angiography were recruited. Blood lipids, other baseline characteristics, and clinical information were investigated in this study. In addition, low-density lipoprotein cholesterol (LDL-C) subfractions were classified and quantified using the Lipoprint system. Based on these data, we performed comprehensive analyses to investigate the risk factors for CAD development and to predict CAD risk. Results: Triglyceride, LDLC-3, LDLC-4, LDLC-5, LDLC-6, and total small and dense LDL-C were significantly higher in the CAD patients than those in the controls, whereas LDLC-1 and high-density lipoprotein cholesterol (HDL-C) had significantly lower levels in the CAD patients. Logistic regression analysis identified male [odds ratio (OR) = 2.875, P < 0.001], older age (OR = 1.018, P = 0.025), BMI (OR = 1.157, P < 0.001), smoking (OR = 4.554, P < 0.001), drinking (OR = 2.128, P < 0.016), hypertension (OR = 4.453, P < 0.001), and diabetes mellitus (OR = 8.776, P < 0.001) as clinical risk factors for CAD development. Among blood lipids, LDLC-3 (OR = 1.565, P < 0.001), LDLC-4 (OR = 3.566, P < 0.001), and LDLC-5 (OR = 6.866, P < 0.001) were identified as risk factors. To predict CAD risk, six machine learning models were constructed. The XGboost model showed the highest AUC score (0.945121), which could distinguish CAD patients from the controls with a high accuracy. LDLC-4 played the most important role in model construction. Conclusions: The established models showed good performance for CAD risk prediction, which can help screen high-risk CAD patients in asymptomatic population, so that further examination and prevention treatment might be taken before any sudden or serious event.

3D simulation of radiographic projections to test and reduce the effect of pelvic tilt on the accuracy of cross-table lateral radiography.

BACKGROUND: Cross-table lateral (CL) radiography is a convenient and feasible method to assess cup version angle (VA) after total hip arthroplasty; However, pelvic tilt (PT) may contribute to its measurement inaccuracy. How PT affects CL radiographic measurements have not been well studied. We sought (1) to determine the effect of the PT on cup version measurement on CL radiography and (2) to develop a method for reducing measurement errors caused by the PT. METHODS: We used 3D technique to construct standard model and capture CL radiography simulation. A linear regression model was created to analyze the relationship between PT and VA. CL radiography and computed tomography (CT) were performed for the enrolled patients after surgery. The consistency between CL and CT measurements were verified by intra-class correlation coefficient (ICC). RESULTS: There was a high correlation between the VA and PT. For each 1-degree increased in the PT, the VA decreased by 0.76° (R2 = 0.995, p < 0.001). Based on the data, we created a corrective formula to convert the radiographic measurements into values approximating the actual VA under a natural pelvic position. The VA measurements corrected by our equation was in high agreement with the CT-measured values with reference to the corresponding PT (ICC = 0.988, p < 0.001), which was in sharp contrast to that without PT control (ICC = 0.454, p = 0.203). CONCLUSIONS: The PT may contribute to cup version measurement inaccuracies on CL radiography. Our mathematical algorithm can serve as a reliable method to improve the accuracy of CL radiography.

Exosomal lncRNAs NONMMUT000375.2 and NONMMUT071578.2 derived from titanium particle treated RAW264.7 cells regulate osteogenic differentiation of MC3T3-E1 cells.

Periprosthetic osteolysis and the subsequent aseptic loosening can lead to the failure of joint replacement. Wear particles are well known to be the initiative cause inducing osteolysis through enhancing osteoclast-mediated bone resorption and reducing osteogenic differentiation. The purpose of this study was to investigate the effects of osteoclast-secreted exosomal long noncoding RNAs (lncRNAs) on osteogenesis in the process of particle-induced osteolysis. RAW264.7 cells were treated by titanium particles (TI). The inflammatory cytokines were increased, and expression of Receptor Activator of Nuclear Factor-κB and Nuclear factor of activated T cells c1 were also increased, indicating osteoclast differentiation occurred. The purified exosomes from RAW264.7 cells induced with TI inhibited osteogenic differentiation of MC3T3-E1 cells. RNA sequencing generated lncRNAs expression profiles (458 up-regulated and 1641 down-regulated) of the exosomes derived from RAW264.7 cells treated with TI. Based on the results of gene ontology/Kyoto Encyclopedia of Genes and Genomes analysis and quantitative real time polymerase chain reaction validation, we confirmed two candidate lncRNAs, NONMMUT000375.2 and NONMMUT071578.2. The regulation network presented that some vital genes involved in osteoclast differentiation, such as Bcl2, Wnt11, TGF-ß, and Pdk1, were under the regulation of NONMMUT000375.2 and NONMMUT071578.2. Taken together, exosomes derived from TI treated RAW264.7 cells inhibit the osteogenic activity of MC3T3-E1 cells. Exosomal lncRNAs, NONMMUT000375.2 and NONMMUT071578.2 may potentially play their roles in promoting osteoclast differentiation and suppressing osteogenesis, which aggravates the osteoclastogenesis/osteogenesis imbalance.

A meta-analysis of autologous transplantation for newly diagnosed multiple myeloma in the era of novel agents.

To evaluate the role of high-dose melphalan plus autologous stem-cell transplantation (ASCT) as consolidation therapy for patients with newly diagnosed multiple myeloma (NDMM) in the era of novel agents, we undertook this meta-analysis. Medline, Embase, the Cochrane controlled trials register, the SCI, ASH, EHA, and ASCO were searched for clinical trials including high-dose chemotherapy plus ASCT for patients with NDMM. Finally, we identified four RCTs of ASCT versus novel agents based consolidations, and 10 single-arm prospective trials of ASCT alone. Pooled analysis indicated that response quality improved further after ASCT in the era of novel agents (≥CR rates of 13% pre-ASCT versus 29% post-ASCT, p = .003). When compared to novel agents containing consolidation regimens, high-dose chemotherapy plus ASCT significantly improved progression-free survival (PFS) (HR =0.56, p < .001). No significant difference in overall survival (OS) was found between them (HR =0.66, p = .22). Of note, subgroup analysis indicated that ASCT could significantly improve OS (HR =0.49, p = .0004) when compared to alkylating agent-based regimens plus lenalidomide consolidation. In summary, response quality and PFS improved further over ASCT in the era of novel agents. ASCT could improve survival than alkylating agent-based regimens plus lenalidomide consolidations for patients with NDMM.

Wear particles enhance autophagy through up-regulation of CD147 to promote osteoclastogenesis.

OBJECTIVES: The study aimed to uncover the underlying mechanism linking wear particles to osteoclast differentiation, and we explored the effect of titanium particles of different sizes on CD147 expression and autophagy in macrophages. MATERIALS AND METHODS: Effects of titanium particles on CD147 and RANKL mRNA were detected by QPCR; protein level of CD147 and Beclin-1 were detected by Western blot; soluble RANKL were detected by ELISA. To determine the effect of CD147 and autophagy, KG-1a cells were transfected with siRNA-CD147 or treated with autophagy inhibitor CQ (chloroquine), and then co-cultured with different sizes of titanium particles. RESULTS: Our results showed that 0.2-1.2 µm and 1.2-10 µm titanium particles up-regulate CD147 to activate autophagy, which increase the level of soluble RANKL to promote osteoclastogenesis. Suppression of CD147 with siRNA could diminish particle-induced autophagy and soluble RANKL expression. In addition, CQ could dramatically reduce particle-induced soluble RANKL expression. CONCLUSION: Our findings suggested a possible mechanism underlying wear debris-induced osteolysis and identified CD147 as a potential therapeutic target in aseptic loosening.

An integrative analysis of DNA methylation in osteosarcoma.

BACKGROUND: The study aimed to analyze aberrantly methylated genes, relevant pathways and transcription factors (TFs) in osteosarcoma (OS) development. METHODS: Based on the DNA methylation microarray data GSE36002 that were downloaded from GEO database, the differentially methylated genes in promoter regions were identified between OS and normal samples. Pathway and function enrichment analyses of differentially methylated genes was performed. Subsequently, protein-protein interaction (PPI) network was constructed, followed by identification of cancer-associated differentially methylated genes and significant differentially methylated TFs. RESULTS: A total of 1379 hyper-methylation regions and 169 hypo-methylation regions in promoter regions were identified in OS samples compared to normal samples. The differentially hyper-methylated genes were significantly enriched in Neuroactive ligand-receptor interaction pathway, and Peroxisome proliferator activated receptor (PPAR) signaling pathway. The differentially hypo-methylated genes were significantly enriched in Toll-like receptor signaling pathway. In PPI network, signal transducers and activators of transcription (STAT3) had high degree (degree=21). MAX interactor 1, dimerization protein (MXI1), STAT3 and T-cell acute lymphocytic leukemia 1 (TAL1) were significant TFs enriched with target genes in OS samples. They were found to be cancer-associated and hyper-methylated in OS samples. CONCLUSION: Neuroactive ligand-receptor interaction, PPAR signaling, Toll-like receptor signaling pathways are implicated in OS. MXI1, STAT3, and TAL1 may be important TFs involved in OS development.

Neurological teratogenic effects of antiepileptic drugs during pregnancy.

Epilepsy is one of the few neurologic disorders that requires a constant treatment during pregnancy. Epilepsy affects 0.3-0.8% of pregnant women. Prescription of antiepileptic drugs (AEDs) to pregnant women with epilepsy requires monitoring and maintaining a balance between limiting seizures and decreasing fetal exposure to the potential teratogenic effects. AEDs are also commonly used for psychiatric disorders, pain disorders, and migraines. The types of malformations that can result in fetuses exposed to AEDs include minor anomalies, major congenital malformations, intrauterine growth retardation, cognitive dysfunction, low IQ, microcephaly, and infant mortality. In the present review, we analyzed and summarized the current understanding of neurological development in fetuses that are exposed to various AEDs administered to pregnant epileptic women.