Intraspecific and Intrageneric Genomic Variation across Three Sedum Species (Crassulaceae): A Plastomic Perspective.

Sedum is the largest succulent genus in Crassulaceae. Because of predominant maternal inheritance, little recombination, and slow evolution, plastomes can serve as powerful super barcodes for inter- or intra-species phylogenetic analyses. While previous research has focused on plastomes between Sedum species, intra-species studies are scarce. Here, we sequenced plastomes from three Sedum species (Sedum alfredii, Sedum plumbizincicola, and Sedum japonicum) to understand their evolutionary relationships and plastome structural evolution. Our analyses revealed minimal size and GC content variation across species. However, gene distribution at IR boundaries, repeat structures, and codon usage patterns showed diversity at both inter-specific and intra-specific levels. Notably, an rps19 gene expansion and a bias toward A/T-ending codons were observed. Codon aversion motifs also varied, potentially serving as markers for future studies. Phylogenetic analyses confirmed the non-monophyly of Sedum and divided the Acre clade into two groups. Individuals from the same species clustered together, with strong support for the relationships between S. alfredii, S. tricarpum, and S. plumbizincicola. Additionally, S. japonicum clearly affiliates with the Acre clade. This study provides valuable insights into both intra-specific and intra-generic plastome variation in Sedum, as well as overall plastome evolution within the genus.

Prediction of HER2 Expression in Gastric Adenocarcinoma Based On Preoperative Noninvasive Multimodal 18F-FDG PET/CT Imaging.

RATIONALE AND OBJECTIVES: This study aims to investigate the role of a flourine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) multimodal radiomics model in predicting the status of human epidermal growth factor receptor 2 (HER2) expression preoperatively in cases of gastric adenocarcinoma. MATERIALS AND METHODS: This retrospective study included 133 patients with gastric adenocarcinoma who were classified into training (n = 93) and validation (n = 40) cohorts in a ratio of 7:3. Features were selected using Least Absolute Shrinkage and Selection Operator and Extreme Gradient Boosting (XGBoost) methods; further, prediction models were constructed using logistic regression and XGBoost. These models were evaluated and validated using area under the curve (AUC), decision curves, and calibration curves to select the best-performing model. RESULTS: Six different models were established to predict HER2 expression. Among these, the comprehensive model, which integrates seven clinical features, one CT feature, and five PET features, demonstrated AUC values of 0.95 (95% confidence interval [CI]: 0.89-1.00) and 0.76 (95% CI: 0.52-1.00) in the training and validation cohorts, respectively. Compared with other models, this model exhibited a superior net benefit on the decision curve and demonstrated good alignment agreement with the observed values on the calibration curve. Based on these findings, we constructed a nomogram for visualizing the model, providing a noninvasive preoperative method for predicting HER2 expression. CONCLUSION: The preoperative 18F-FDG PET/CT multimodal radiomics model can effectively predict HER2 expression in patients with gastric adenocarcinoma, thereby guiding clinical decision-making and advancing the field of precision medicine.

Phylogenomics and plastomics offer new evolutionary perspectives on Kalanchoideae (Crassulaceae).

BACKGROUND AND AIMS: Kalanchoideae is one of three subfamilies within Crassulaceae and contains four genera. Despite previous efforts, the phylogeny of Kalanchoideae remains inadequately resolved with persistent issues including low support, unstructured topologies and polytomies. This study aimed to address two central objectives: (1) resolving the pending phylogenetic questions within Kalanchoideae by using organelle-scale 'barcodes' (plastomes) and nuclear data; and (2) investigating interspecific diversity patterns among Kalanchoideae plastomes. METHODS: To explore the plastome evolution in Kalanchoideae, we newly sequenced 38 plastomes representing all four constituent genera (Adromischus, Cotyledon, Kalanchoe and Tylecodon). We performed comparative analyses of plastomic features, including GC and gene contents, gene distributions at the IR (inverted repeat) boundaries, nucleotide divergence, plastomic tRNA (pttRNA) structures and codon aversions. Additionally, phylogenetic inferences were inferred using both the plastomic dataset (79 genes) and nuclear dataset (1054 genes). KEY RESULTS: Significant heterogeneities were observed in plastome lengths among Kalanchoideae, strongly correlated with LSC (large single copy) lengths. Informative diversities existed in the gene content at SSC/IRa (small single copy/inverted repeat a), with unique patterns individually identified in Adromischus leucophyllus and one major Kalanchoe clade. The ycf1 gene was assessed as a shared hypervariable region among all four genera, containing nine lineage-specific indels. Three pttRNAs exhibited unique structures specific to Kalanchoideae and the genera Adromischus and Kalanchoe. Moreover, 24 coding sequences revealed a total of 41 lineage-specific unused codons across all four constituent genera. The phyloplastomic inferences clearly depicted internal branching patterns in Kalanchoideae. Most notably, by both plastid- and nuclear-based phylogenies, our research offers the first evidence that Kalanchoe section Eukalanchoe is not monophyletic. CONCLUSIONS: This study conducted comprehensive analyses on 38 newly reported Kalanchoideae plastomes. Importantly, our results not only reconstructed well-resolved phylogenies within Kalanchoideae, but also identified highly informative unique markers at the subfamily, genus and species levels. These findings significantly enhance our understanding of the evolutionary history of Kalanchoideae.

Masked Conditional Variational Autoencoders for Chromosome Straightening.

Karyotyping is of importance for detecting chromosomal aberrations in human disease. However, chromosomes easily appear curved in microscopic images, which prevents cytogeneticists from analyzing chromosome types. To address this issue, we propose a framework for chromosome straightening, which comprises a preliminary processing algorithm and a generative model called masked conditional variational autoencoders (MC-VAE). The processing method utilizes patch rearrangement to address the difficulty in erasing low degrees of curvature, providing reasonable preliminary results for the MC-VAE. The MC-VAE further straightens the results by leveraging chromosome patches conditioned on their curvatures to learn the mapping between banding patterns and conditions. During model training, we apply a masking strategy with a high masking ratio to train the MC-VAE with eliminated redundancy. This yields a non-trivial reconstruction task, allowing the model to effectively preserve chromosome banding patterns and structure details in the reconstructed results. Extensive experiments on three public datasets with two stain styles show that our framework surpasses the performance of state-of-the-art methods in retaining banding patterns and structure details. Compared to using real-world bent chromosomes, the use of high-quality straightened chromosomes generated by our proposed method can improve the performance of various deep learning models for chromosome classification by a large margin. Such a straightening approach has the potential to be combined with other karyotyping systems to assist cytogeneticists in chromosome analysis.

Genome evolution of Buchnera aphidicola (Gammaproteobacteria): Insights into strand compositional asymmetry, codon usage bias, and phylogenetic implications.

Taxa of Buchnera aphidicola (hereafter "Buchnera") are mutualistic intracellular symbionts of aphids, known for their remarkable biological traits such as genome reduction, strand compositional asymmetry, and symbiont-host coevolution. With the growing availability of genomic data, we performed a comprehensive analysis of 103 genomes of Buchnera strains from 12 host subfamilies, focusing on the genomic characterizations, codon usage patterns, and phylogenetic implications. Our findings revealed consistent features among all genomes, including small genome sizes, low GC contents, and gene losses. We also identified strong strand compositional asymmetries in all strains at the genome level. Further investigation suggested that mutation pressure may have played a crucial role in shaping codon usage of Buchnera. Moreover, the genomic asymmetries were reflected in asymmetric codon usage preferences within chromosomal genes. Notably, the levels of these asymmetries were varied among strains and were significantly influenced by the degrees of genome shrinkages. Lastly, our phylogenetic analyses presented an alternative topology of Aphididae, based on the Buchnera symbionts, providing robust confirmation of the paraphylies of Eriosomatinae, and Macrosiphini. Our objectives are to further understand the strand compositional asymmetry and codon usage bias of Buchnera taxa, and provide new perspectives for phylogenetic studies of Aphididae.

[Preliminary study on the regulation of acute myeloid leukemia by FLT3 gene expression].

OBJECTIVE: To assess the influence of FLT3 expression on the prognosis of patients with acute myeloid leukemia (AML) by cell experiment and clinical data analysis. METHODS: Models for FLT3 over-expression and interference-expression in AML cells were constructed. The level of BAK gene expression and its protein product was determined, along with the proliferation and apoptosis of leukemia cells. FLT3 gene expression and FLT3-ITD variant were determined among patients with newly diagnosed AML. RESULTS: Compared with the interference-expression group, the level of BAK gene expression and its protein in FLT3 over-expression AML cells was significantly lower (P < 0.001), which also showed significantly faster proliferation (P < 0.001) and lower rate of apoptosis (P < 0.001). The expression level of FLT3 gene among patients with newly diagnosed AML was also significantly higher compared with the healthy controls (P < 0.001). The FLT3 gene expression of FLT3-ITD positive AML patients was higher than that of FLT3-WT patients (P = 0.002). Survival analysis showed that AML patients with high FLT3 expression in the medium-risk group had a lower complete remission rate and overall survival rate compared with those with a low FLT3 expression (P < 0.001). CONCLUSION: Over-expression of FLT3 may influence the course of AML by promoting the proliferation of leukemia cells and inhibiting their apoptosis, which in turn may affect the prognosis of patients and serve as a negative prognostic factor for AML.

In vitro comparative study of multimodal imaging nano-assembled microspheres with two clinical drug-eluting beads loaded with doxorubicin.

DC Beads and CalliSpheres are commonly used microspheres in clinical transcatheter arterial chemoembolization, but these microspheres cannot be visualized by themselves. Therefore, in our previous study, we developed multimodal imaging nano-assembled microspheres (NAMs), which are visualized under CT/MR and the location of embolic microspheres can be determined during postoperative review, facilitating the evaluation of embolic areas and guiding subsequent treatment. Moreover, the NAMs can be carried with positively and negatively charged drugs, increasing the choice of drugs. Systematic comparative analysis of the pharmacokinetics of NAMs with commercially available DC Bead and CalliSpheres microspheres is important for evaluating the clinical application of NAMs. In our study, we compared the similarities and differences between NAMs and two drug-eluting beads (DEBs) in respect to drug loading capacity, drug release profiles, diameter variation and morphological characteristics. The results indicate that NAMs had good drug delivery and release characteristics as well as DC Bead and CalliSpheres in vitro experimental stage. Therefore, NAMs have a good application prospect in transcatheter arterial chemoembolization treatment of hepatocellular carcinoma.

Ten Plastomes of Crassula (Crassulaceae) and Phylogenetic Implications.

The genus Crassula is the second-largest genus in the family Crassulaceae, with about 200 species. As an acknowledged super-barcode, plastomes have been extensively utilized for plant evolutionary studies. Here, we first report 10 new plastomes of Crassula. We further focused on the structural characterizations, codon usage, aversion patterns, and evolutionary rates of plastomes. The IR junction patterns-IRb had 110 bp expansion to rps19-were conservative among Crassula species. Interestingly, we found the codon usage patterns of matK gene in Crassula species are unique among Crassulaceae species with elevated ENC values. Furthermore, subgenus Crassula species have specific GC-biases in the matK gene. In addition, the codon aversion motifs from matK, pafI, and rpl22 contained phylogenetic implications within Crassula. The evolutionary rates analyses indicated all plastid genes of Crassulaceae were under the purifying selection. Among plastid genes, ycf1 and ycf2 were the most rapidly evolving genes, whereas psaC was the most conserved gene. Additionally, our phylogenetic analyses strongly supported that Crassula is sister to all other Crassulaceae species. Our findings will be useful for further evolutionary studies within the Crassula and Crassulaceae.

Structural Diversities and Phylogenetic Signals in Plastomes of the Early-Divergent Angiosperms: A Case Study in Saxifragales.

As representative of the early-divergent groups of angiosperms, Saxifragales is extremely divergent in morphology, comprising 15 families. Within this order, our previous case studies observed significant structural diversities among the plastomes of several lineages, suggesting a possible role in elucidating their deep phylogenetic relationships. Here, we collected 208 available plastomes from 11 constituent families to explore the evolutionary patterns among Saxifragales. With thorough comparisons, the losses of two genes and three introns were found in several groups. Notably, 432 indel events have been observed from the introns of all 17 plastomic intron-containing genes, which could well play an important role in family barcoding. Moreover, numerous heterogeneities and strong intrafamilial phylogenetic implications were revealed in pttRNA (plastomic tRNA) structures, and the unique structural patterns were also determined for five families. Most importantly, based on the well-supported phylogenetic trees, evident phylogenetic signals were detected in combinations with the identified pttRNAs features and intron indels, demonstrating abundant lineage-specific characteristics for Saxifragales. Collectively, the results reported here could not only provide a deeper understanding into the evolutionary patterns of Saxifragales, but also provide a case study for exploring the plastome evolution at a high taxonomic level of angiosperms.

The Mitogenome of Sedum plumbizincicola (Crassulaceae): Insights into RNA Editing, Lateral Gene Transfer, and Phylogenetic Implications.

As the largest family within the order Saxifragales, Crassulaceae contains about 34 genera with 1400 species. Mitochondria play a critical role in cellular energy production. Since the first land plant mitogenome was reported in Arabidopsis, more than 400 mitogenomic sequences have been deposited in a public database. However, no entire mitogenome data have been available for species of Crassulaceae to date. To better understand the evolutionary history of the organelles of Crassulaceae, we sequenced and performed comprehensive analyses on the mitogenome of Sedum plumbizincicola. The master mitogenomic circle is 212,159 bp in length, including 31 protein-coding genes (PCGs), 14 tRNA genes, and 3 rRNA genes. We further identified totally 508 RNA editing sites in PCGs, and demonstrated that the second codon positions of mitochondrial genes are most prone to RNA editing events. Notably, by neutrality plot analyses, we observed that the mitochondrial RNA editing events have large effects on the driving forces of plant evolution. Additionally, 4 MTPTs and 686 NUMTs were detected in the mitochondrial and nuclear genomes of S. plumbizincicola, respectively. Additionally, we conducted further analyses on gene transfer, secondary structures of mitochondrial RNAs, and phylogenetic implications. Therefore, the findings presented here will be helpful for future investigations on plant mitogenomes.

Mitogenomic Codon Usage Patterns of Superfamily Certhioidea (Aves, Passeriformes): Insights into Asymmetrical Bias and Phylogenetic Implications.

The superfamily Certhioidea currently comprises five families. Due to the rapid diversification, the phylogeny of Certhioidea is still controversial. The advent of next generation sequencing provides a unique opportunity for a mitogenome-wide study. Here, we first provided six new complete mitogenomes of Certhioidea (Certhia americana, C. familiaris, Salpornis spilonota, Cantorchilus leucotis, Pheugopedius coraya, and Pheugopedius genibarbis). We further paid attention to the genomic characteristics, codon usages, evolutionary rates, and phylogeny of the Certhioidea mitogenomes. All mitogenomes we analyzed displayed typical ancestral avian gene order with 13 protein-coding genes (PCGs), 22 tRNAs, 2 rRNAs, and one control region (CR). Our study indicated the strand-biased compositional asymmetry might shape codon usage preferences in mitochondrial genes. In addition, natural selection might be the main factor in shaping the codon usages of genes. Additionally, evolutionary rate analyses indicated all mitochondrial genes were under purifying selection. Moreover, MT-ATP8 and MT-CO1 were the most rapidly evolving gene and conserved genes, respectively. According to our mitophylogenetic analyses, the monophylies of Troglodytidae and Sittidae were strongly supported. Importantly, we suggest that Salpornis should be separated from Certhiidae and put into Salpornithidae to maintain the monophyly of Certhiidae. Our findings are useful for further evolutionary studies within Certhioidea.

MOOC Behavior Analysis and Academic Performance Prediction Based on Entropy.

In recent years, massive open online courses (MOOCs) have received widespread attention owing to their flexibility and free access, which has attracted millions of online learners to participate in courses. With the wide application of MOOCs in educational institutions, a large amount of learners' log data exist in the MOOCs platform, and this lays a solid data foundation for exploring learners' online learning behaviors. Using data mining techniques to process these log data and then analyze the relationship between learner behavior and academic performance has become a hot topic of research. Firstly, this paper summarizes the commonly used predictive models in the relevant research fields. Based on the behavior log data of learners participating in 12 courses in MOOCs, an entropy-based indicator quantifying behavior change trends is proposed, which explores the relationships between behavior change trends and learners' academic performance. Next, we build a set of behavioral features, which further analyze the relationships between behaviors and academic performance. The results demonstrate that entropy has a certain correlation with the corresponding behavior, which can effectively represent the change trends of behavior. Finally, to verify the effectiveness and importance of the predictive features, we choose four benchmark models to predict learners' academic performance and compare them with the previous relevant research results. The results show that the proposed feature selection-based model can effectively identify the key features and obtain good prediction performance. Furthermore, our prediction results are better than the related studies in the performance prediction based on the same Xuetang MOOC platform, which demonstrates that the combination of the selected learner-related features (behavioral features + behavior entropy) can lead to a much better prediction performance.

Age-related differences of genetic susceptibility to patients with acute lymphoblastic leukemia.

Inherited predispositions to acute lymphoblastic leukemia have been well investigated in pediatric patients, but studies on adults, particularly Chinese patients, are limited. In this study, we conducted a genome-wide association study in 466 all-age Chinese patients with Acute lymphoblastic leukemia (ALL) and 1,466 non-ALL controls to estimate the impact of age on ALL susceptibility in the Chinese population. Among the 17 reported loci, 8 have been validated in pediatric and 1 in adult patients. The strongest association signal was identified at ARID5B locus and gradually decreased with age, while the signal at GATA3 exhibited the opposite trend and significantly impact on adult patients. With genome-wide approaches, germline variants at 2q14.3 rank as the top inherited predisposition to adult patients (e.g., rs73956024, P = 4.3 × 10-5) and separate the genetic risk of pediatric vs. adult patients (P = 3.6 × 10-6), whereas variants at 15q25.3 (e.g., rs11638062) have a similar impact on patients in different age groups (overall P = 2.9 × 10-7). Our analysis highlights the impact of age on genetic susceptibility to ALL in Chinese patients.

Validations of Top and Novel Susceptibility Variants in All-Age Chinese Patients With Acute Lymphoblastic Leukemia.

Through genome-wide association studies (GWAS), multiple inherited predispositions to acute lymphoblastic leukemia (ALL) have been identified in children. Most recently, a novel susceptibility locus at ERG was localized, exhibiting Hispanic-specific manner. In this study, we conducted a replication study to in all-age Chinese patients (N = 451), not only validating the novel ERG locus, but also systematically determining the impact of age on association status of the top GWAS signals. We found that single nucleotide polymorphisms at ARID5B, IKZF1, CEBPE, PIP4K2A were only significantly associated with ALL susceptibility in childhood patients with no BCR-ABL fusion, while GATA3 signal exhibited its significance in adults no matter carrying BCR-ABL fusion or not. Moreover, the novel ERG SNP can be validated in pediatric patients without both BCR-ABL and ETV6-RUNX1 fusion. Our finding suggests the modifying effects of age on genetic predisposition to ALL, and highlights the impact of ERG SNP in Chinese patients.

ARID5B Genetic Polymorphisms Contribute to the Susceptibility and Prognosis of Male Acute Promyelocytic Leukemia.

This study was conducted using TagSNPs to systematically explore the relationship between ARID5B polymorphisms and the occurrence, clinical characterization, and prognosis of acute myeloid leukemia (AML). A total of 569 unrelated AML patients and 410 healthy individuals from West China were recruited, and ARID5B TagSNPs were genotyped using iMLDR® (improved multiplex ligation detection reaction). It was found that the association of ARID5B polymorphisms with AML was most significant in acute promyelocytic leukemia (APL), and exclusively in males, the mutant alleles of rs6415872, rs2393726, rs7073837, rs10821936, and rs7089424 were found to increase the risk of developing APL in men, the odds ratio (OR) were 1.36, 1.74, 1.45, 1.53, and 1.56 (all p < 0.05), respectively. Haplotype analysis revealed that haplotype [AACCG] increased the risk of male APL with an OR of 1.53 (95% confidence interval: 1.10-2.14, p = 0.012). Besides, there was a strong positive additive interaction between rs6415872 and rs10821936, rs7089424, respectively, and cases attributed to the interaction of rs6415872, rs10821936, and rs7089424 accounted for 100%. Furthermore, ARID5B single nucleotide polymorphisms were found associated with clinical features of AML, and rs6415872 was shown to be an independent prognosis factor in APL patients. Besides, dual luciferase report assay showed that rs6415872 may affect the binding activity of PPARG with ARID5B. ARID5B polymorphisms contribute to male APL risk, clinical feature, and prognosis, suggesting the importance of ARDI5B in AML pathogenesis and development, and the gender and subtype preference may prompt some specific mechanisms of ARID5B. Besides, ARID5B polymorphisms might be a potential prognosis biomarker.

Relationship between CXC chemokine receptor 4 expression and prognostic significance in acute myeloid leukemia.

CXC chemokine receptor 4 (CXCR4) expression on acute myeloid leukemia (AML) cells correlated with stromal cell derived factor-1α (SDF-1α) and retained hematopoietic progenitors and leukemia cells within the bone marrow microenvironment. Here, we examined CXCR4 expression in 134 de novo AML and 21 controls by flow cytometry, evaluated the relationship between CXCR4 expression and clinical characteristics, and elucidated the prognostic significance of CXCR4 expression in AML prospectively. We found that the CXCR4 expression was significantly higher in AML patients than controls (P = .000). One hundred thirty four cases of de novo AML patients were divided into 2 groups according to the median of CXCR4 relative fluorescence intensity (RFI). CXCR4 high group (RFI >4.23) had markedly shorter overall survival (OS) and disease-free survival (DFS) than CXCR4 low group (RFI ≤4.23) in 106 AML patients who received chemotherapy (P = .002; .026, respectively). Furthermore, in the 87 non-M3 patients who received induction therapy, there was a significant decrease for OS but not for DFS in the CXCR4 high group (P = .047 and .178, respectively). Moreover, high levels of CXCR4 expression independently increased the risk of relapse in both all AML and non-M3 patients who achieved complete remission (CR) after chemotherapy (odds ratio = 1.090, P = .010; odds ratio = 1.068, P = .048, respectively). Collectively, our data suggest that CXCR4 overexpression was an independent prognostic factor for disease relapse and poorer OS in both all AML and non-M3 patients. CXCR4 expression levels can be determined at disease presentation by the flow rapidly and easily. As such, CXCR4 could be used as a potential therapeutic target in AML patients with poor prognosis.

Combination of IKZF1 deletion and early molecular response show significant roles on prognostic stratification in Philadelphia chromosome-positive acute lymphoblastic leukemia patients.

We retrospectively analyzed the samples collected from 66 patients with Ph+ALL enrolled on ChiCTR-TNRC-09000309 clinical trial. CR rate was 95.5%, and estimated 2-year OS and DFS were 51.7 ± 11.7% and 26.9 ± 11.6%, 3-year OS and DFS were 31.6 ± 12.0% and 23.4 ± 11.6%. By combining IKZF1 deletion and early molecular responses, we redefined the patients as low, intermediate, and high risk 3 groups separately. Patients with double negative in IKZF1 and early molecular response experienced significant superior survival, while patients with double positive would have the worst outcome, and patients who were one or the other with IKZF1 deletion or MRD status had intermediate outcome. Significant differences were found among 3 groups in regard to both OS (p < .001) and DFS (p < .001). Our findings suggest that Ph+ALL is a heterogeneous group of diseases with significantly different prognosis. Combination of IKZF1 deletion and MRD status enable better risk stratification of patients for assignment to optimal therapeutic strategies.

Sequence variations of mitochondrial DNA D-loop region in patients with acute myeloid leukemia.

The aim of the present study was to explore variations of the displacement (D)-loop region in patients with acute myeloid leukemia (AML) and their possible associations with AML pathogenesis. Blood or bone marrow samples from 216 patients with AML (158 AML patients in the first stage, and 58 more patients with AML-M3 for further verification), and 146 healthy controls were collected. Sanger sequencing was performed for the D-loop region ranging between nucleotide (nt)15811 and nt 775. With the exception of mitochondrial microsatellite instability (mtMSI) variations, a total of 2,630 variations in 232 loci were identified with similar variation rates/person in patients with AML and controls when compared with the revised Cambridge reference sequence (8.54±2.14 vs. 8.77±2.15; P=0.366). A positive association between AML and variation-T152C was identified, which occurred more frequently in patients with AML compared with in controls [26.6 vs. 17.1%; P=0.048; odds ratio (OR), 1.752; 95% confidence interval (CI), 1.004-3.058]. Furthermore, T152C was identified to be associated with promyelocytic leukemia-retinoic acid receptor α(PML-RARα) and French-American-British AML subtypes, with a tendency to occur in patients with AML-M3. The AML-M3 sample size was extended by 58 cases, and it was identified that the T152C variation rate was significantly higher in patients with AML-M3 compared with that of controls (41.0 vs. 17.1%; P<0.001; OR, 3.228; 95% CI, 1.714-6.079). However, no association was identified between the T152C variation and clinical characteristics, or chemotherapy response in patients with AML-M3. In addition, the mtMSIs, including D310, mt514-523 (CA)n and T16189C, demonstrated no association with AML risk. Together, the results of the present study suggest that the mitochondrial DNA D-loop region is high variable, and that T152C is associated with AML risk, particularly regarding the M3 subtype. T152C mayparticipate in AML pathogenesis and may be a diagnostic biomarker; however further studies with larger sample sizes are required in order to verify its value.

Influence of SCARB1 gene SNPs on serum lipid levels and susceptibility to coronary heart disease and cerebral infarction in a Chinese population.

The SCARB1 gene encodes human scavenger receptor class B type I (SR-BI), the primary receptor for high-density lipoprotein (HDL)- cholesteryl ester uptake, and polymorphisms in this gene may influence SR-BI protein expression and serum lipid levels, modulating susceptibility to coronary heart disease (CHD) and cerebral infarction (CI). Therefore, we investigated the association between singlenucleotide polymorphisms (SNPs) in the SCARB1 gene and serum lipid levels as well as risk of CHD and CI in the Chinese Han population. Genotypes in 295 CHD patients, 302 CI patients and 312 healthy controls matched for age and gender were determined by high-resolution melting (HRM). Among the 5 SNPs investigated in this study, rs10846744 and rs2278986 were significantly associated with CHD risk. The frequency of the C allele for rs10846744 and that of the T allele for rs2278986 appeared to be significantly increased in the CHD group (OR: 1.416, 95%CI: 1.128-1.778, P=0.0058 and OR: 1.681, 95%CI: 1.327-2.130, P<0.0001, respectively). CHD patients with genotypes CC and CG for rs10846744 had a higher HDL-c level than those with genotype GG, and CHD patients with genotypes CC and CT for the rs2278986 SNP had a higher HDL-c level compared to those with the TT allele. The other 3 SNPs, rs5888, rs10744182 and rs838893, showed no significant association with serum lipid levels and CHD or CI risk in the Chinese population. The CCCTT and CCTTC haplotypes of rs5888, rs10846744, rs10744182, rs2278986 and rs838893 appear to significantly increase CHD risk, whereas the CGTTC, CCTCT and TGCTC haplotypes appear to significantly reduce risk. Overall, the CCTTC and TGTTC haplotypes acted as a significant risk for CI, with the CGCTC and CCCCT haplotypes conferring significantly reduced risk. These results suggest that SCARB1 gene polymorphisms may contribute to genetic susceptibility to CHD; in particular, the C allele of rs10846744 and the C allele of rs2278986 may serve as risk and protective factors for CHD, respectively.

Regulatory network of GATA3 in pediatric acute lymphoblastic leukemia.

GATA3 polymorphisms were reported to be significantly associated with susceptibility of pediatric B-lineage acute lymphoblastic leukemia (ALL), by impacting on GATA3 expression. We noticed that ALL-related GATA3 polymorphism located around in the tissue-specific enhancer, and significantly associated with GATA3 expression. Although the regulatory network of GATA3 has been well reported in T cells, the functional status of GATA3 is poorly understood in B-ALL. We thus conducted genome-wide gene expression association analyses to reveal expression associated genes and pathways in nine independent B-ALL patient cohorts. In B-ALL patients, 173 candidates were identified to be significantly associated with GATA3 expression, including some reported GATA3-related genes (e.g., ITM2A) and well-known tumor-related genes (e.g., STAT4). Some of the candidates exhibit tissue-specific and subtype-specific association with GATA3. Through overexpression and down-regulation of GATA3 in leukemia cell lines, several reported and novel GATA3 regulated genes were validated. Moreover, association of GATA3 expression and its targets can be impacted by SNPs (e.g., rs4894953), which locate in the potential GATA3 binding motif. Our findings suggest that GATA3 may be involved in multiple tumor-related pathways (e.g., STAT/JAK pathway) in B-ALL to impact leukemogenesis through epigenetic regulation.