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The given text is a study published in the Blood Cancer Journal that explores the phenomenon of lineage switch in leukemia, where cells change from one lineage to another. The study includes 33 cases of acute leukemia that underwent lineage switch and provides valuable insights into the clinicopathological features and genetic drivers of this event. The findings suggest that certain risk factors, such as specific genetic abnormalities and the presence of a previous chronic myeloid malignancy, may increase the likelihood of lineage switch. The study emphasizes the importance of early detection and potential benefits of early allogeneic stem cell transplant in these cases, while also highlighting the need for further research to develop preventive and therapeutic strategies. [Extracted from the article]

Genomic imprinting is an epigenetic regulation mechanism in mammals resulting in the parentally dependent monoallelic expression of genes. Imprinting disorders in humans are associated with several congenital syndromes and cancers and remain the focus of many medical studies. Cattle is a better model organism for investigating human embryo development than mice. Imprinted genes usually cluster on chromosomes and are regulated by different methylation regions (DMRs) located in imprinting control regions that control gene expression in cis. There is an imprinted locus on human chromosome 16q24.1 associated with congenital lethal developmental lung disease in newborns. However, genomic imprinting on bovine chromosome 18, which is homologous with human chromosome 16 has not been systematically studied. The aim of this study was to analyze the allelic expressions of eight genes (CDH13, ATP2C2, TLDC1, COTL1, CRISPLD2, ZDHHC7, KIAA0513, and GSE1) on bovine chromosome 18 and to search the DMRs associated gene allelic expression. Three transcript variants of the ZDHHC7 gene (X1, X2, and X5) showed maternal imprinting in bovine placentas. In addition, the monoallelic expression of X2 and X5 was tissue-specific. Five transcripts of the KIAA0513 gene showed tissue- and isoform-specific monoallelic expression. The CDH13, ATP2C2, and TLDC1 genes exhibited tissue-specific imprinting, however, COTL1, CRISLPLD2, and GSE1 escaped imprinting. Four DMRs, established after fertilization, were found in this region. Two DMRs were located between the ZDHHC7 and KIAA0513 genes, and two were in exon 1 of the CDH13 and ATP2C2 genes, respectively. The results from this study support future studies on the molecular mechanism to regulate the imprinting of candidate genes on bovine chromosome 18. [ABSTRACT FROM AUTHOR]

Approximately 15–25% pregnant women end with miscarriage in the world. Environmental BaP (benzo(a)pyrene) and its terminal metabolite BPDE (benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide) may result in the dysfunctions of trophoblast cells, which might further lead to RM (recurrent miscarriage). However, potential mechanisms remain unelucidated. In this work, we identified a novel lnc-HZ05 highly expressed and a novel miR-hz05 lowly expressed in both trophoblast cells exposed to BPDE and human RM tissues. MiR-hz05 reduces FOXO3a mRNA level by weakening its mRNA stability. Lnc-HZ05 increases the expression of FOXO3a by acting as a ceRNA for miR-hz05, and then increases P21 level and reduces CDK2 level. Thus, cell cycle is arrested at G0/G1 phase and trophoblast proliferation is inhibited. Lnc-HZ05 harboring wild-type binding site for miR-hz05, but not its mutant site, could upregulate FOXO3a expression. In normal trophoblast cells, relatively less lnc-HZ05 and more miR-hz05 activate FOXO3a/P21/CDK2 pathway and promote trophoblast proliferation, giving normal pregnancy. In RM tissues and BPDE-treated human trophoblast cells, lnc-HZ05 is increased and miR-hz05 is reduced, both of which suppress this pathway and inhibit cell proliferation, and finally lead to miscarriage. Thus, lnc-HZ05 and miR-hz05 simultaneously regulate cell cycle and proliferation of BPDE-exposed trophoblast cells and miscarriage, providing new perspectives and clinical understandings in the occurrence of unexplained miscarriage. [ABSTRACT FROM AUTHOR]

Increasing evidences have shown that pregnant women might miscarry after exposure with environmental BaP (benzo(a)pyrene). Additionally, BPDE (benzo(a)pyren-7,8-dihydrodiol-9,10-epoxide), the ultimate metabolite of BaP, could induce dysfunctions of human trophoblast cells. However, it is rarely correlated between miscarriage and trophoblast dysfunctions. Moreover, their underlying mechanisms are still largely unidentified. In this study, a novel lncRNA (long non-coding RNA), lnc-HZ08, was identified to be highly expressed in human recurrent miscarriage (RM) tissues and in BPDE-treated human trophoblast cells. Lnc-HZ08 acts as a RNA scaffold to interact with both PI3K and its ubiquitin ligase CBL (Cbl proto-oncogene), enhances their protein interactions, and promotes PI3K ubiquitin degradation. In RM tissues and BPDE-treated trophoblast cells, DNA methylation level in lnc-HZ08 promoter region was reduced, which promotes estrogen receptor 1 (ER)–mediated lnc-HZ08 transcription. Subsequently, this upregulated lnc-HZ08 downregulated PI3K level, suppressed PI3K/p-AKT/p-P21/CDK2 pathway, and thus weakened proliferation, migration, and invasion of human trophoblast cells, which further induces miscarriage. These results may provide novel scientific and clinical insights in the occurrence of unexplained miscarriage. [ABSTRACT FROM AUTHOR]

For the airborne pod strapdown inertial navigation system, it is necessary to use the host aircraft's inertial navigation system for the transfer alignment as quickly and accurately as possible in the flight process of the aircraft. The purpose of this paper is to propose an adaptive transfer alignment method based on the observability analysis for the strapdown inertial navigation system, which is able to meet the practical need of maintaining the navigation accuracy of the airborne pod. The observability of each state variable is obtained by observability analysis of system state variables. According to the weight of the observability, a transfer alignment filter algorithm based on adaptive adjustment factor is constructed to reduce the influence of weak observability state variables on the whole filter, which can improve the estimation accuracy of transfer alignment. Simulations and experiment tests of the airborne pod and the master strapdown inertial navigation systems show that the adaptive transfer alignment method based on the observability analysis can overcome the shortage of the weak observability state variables, so as to improve the alignment and the navigation performance in practical applications, thus improving the adaptability of the airborne pod. [ABSTRACT FROM AUTHOR]

The AXL protein is a receptor tyrosine kinase and is often implicated in proliferation, migration and therapy resistance in various cancers. The AXL gene in humans is maternally expressed and paternally imprinted with differentially methylated regions (DMR) surrounding the promoter region. However, the imprinting status and epigenetic regulation of AXL gene in cattle remain unclear. Therefore, we explored the molecular structure along with the patterns of allelic expression and DNA methylation of the bovine AXL gene. First, the complete cDNA sequence of bovine AXL was gathered by Sanger method, from transcripts obtained from RT-PCR, 5′ and 3′ -RACE. In silico BLAST alignments showed that the longest mRNA sequence of bovine AXL consists of 19 exons and encodes a protein of 887 amino acids. We further analyzed the allelic expression of bovine AXL by employing single-nucleotide polymorphism (SNP)-based sequencing method. A SNP site (GenBank Accession no: rs210020651) found in exon 7 allowed us to distinguish the two parental alleles. Monoallelic expression of AXL was observed in four adult bovine tissues (heart, liver, spleen and fat), while biallelic expression was found in the other adult tissues such as the lung, kidney, muscle, brain and placenta. To determine whether the DNA methylation played a role in the tissue-specific imprinting of bovine AXL, we performed bisulfite sequencing of two regions: region 1 was a CpG island (CGI) in AXL promoter, mapping to 643 bp upstream of the transcription start site of AXL 5′-v1 transcripts, while region two was homologous to the region of human AXL DMR, with 10 CpG sites overlapping the first translation start site (TSS1) of bovine AXL. In region 2, DNA from both monoallelic and biallelic expressed tissues were mostly found to be completely unmethylated. However, tissue-specific differential methylation patterns were found in monoallelic expressed tissues such as the heart and liver while hypomethylation was noted in the promoter CpG island in biallelic expressed tissues such as the lung. These observations demonstrated that the tissue-specific monoallelic expression of bovine AXL is dependent on the DNA methylation of its promoter region. [ABSTRACT FROM AUTHOR]

Purpose of Review: Minimal or measurable residual disease (MRD) detected by multiparameter flow cytometry (MFC) is an independent prognostic indicator in acute leukemia. However, the predictive value of MFC MRD is affected by technical challenges, interpretive complexities, and inadequate standardization, particularly in acute myeloid leukemia (AML). Here, we critically review the methodological principles of the MFC MRD assay and discuss clinical implications of MRD.Recent Findings: Key components of MFC MRD assays to be discussed include the principles of MFC, panel selection, analysis approaches, level of quantifiable MRD and calculation, reporting, and areas of improvements. Key components of clinical implications include context-dependent detection threshold and the integral role of MRD assessment by MFC in the era of ever-expanding molecular testing.Summary: With advancements in technology and standardization, MFC along with molecular assays will continue to play an important role in MRD assessment to evaluate treatment response and risk stratification. [ABSTRACT FROM AUTHOR]

Imprinted genes are characterized by monoallelic expression that is dependent on parental origin. Comparative analysis of imprinted genes between species is a powerful tool for understanding the biological significance of genomic imprinting. The slc38a4 gene encodes a neutral amino acid transporter and is identified as imprinted in mice. In this study, the imprinting status of SLC38A4 was assessed in bovine adult tissues and placenta using a polymorphism-based approach. Results indicate that SLC38A4 is not imprinted in eight adult bovine tissues including heart, liver, spleen, lung, kidney, muscle, fat, and brain. It was interesting to note that SLC38A4 showed polymorphic status in five heterogeneous placentas, with three exhibiting paternal monoallelic expression and two exhibiting biallelic expression. Monoallelic expression of imprinted genes is generally associated with allele-specific differentially methylation regions (DMRs) of CpG islands (CGIs)-encompassed promoter; therefore, the DNA methylation statuses of three CGIs in the SLC38A4 promoter and exon 1 region were tested in three placentas (two exhibiting paternal monoallelic and one showing biallelic expression of SLC38A4) and their corresponding paternal sperms. Unexpectedly, extreme hypomethylation (< 3%) of the DNA was observed in all the three detected placentas and their corresponding paternal sperms. The absence of DMR in bovine SLC38A4 promoter region implied that DNA methylation of these three CGIs does not directly or indirectly affect the polymorphic imprinting of SLC38A4 in bovine placenta. This suggested other epigenetic features other than DNA methylation are needed in regulating the imprinting of bovine SLC38A4, which is different from that of mouse with respect to a DMR existence at the mouse’s slc38a4 promoter region. Although further work is needed, this first characterization of polymorphic imprinting status of SLC38A4 in cattle placenta provides valuable information on investigating the genomic imprinting phenomenon itself. [ABSTRACT FROM AUTHOR]

Immune checkpoint blockade therapy has been successful in treating some types of cancer but has not shown clinical benefits for treating leukaemia1. This result suggests that leukaemia uses unique mechanisms to evade this therapy. Certain immune inhibitory receptors that are expressed by normal immune cells are also present on leukaemia cells. Whether these receptors can initiate immune-related primary signalling in tumour cells remains unknown. Here we use mouse models and human cells to show that LILRB4, an immunoreceptor tyrosine-based inhibition motif-containing receptor and a marker of monocytic leukaemia, supports tumour cell infiltration into tissues and suppresses T cell activity via a signalling pathway that involves APOE, LILRB4, SHP-2, uPAR and ARG1 in acute myeloid leukaemia (AML) cells. Deletion of LILRB4 or the use of antibodies to block LILRB4 signalling impeded AML development. Thus, LILRB4 orchestrates tumour invasion pathways in monocytic leukaemia cells by creating an immunosuppressive microenvironment. LILRB4 represents a compelling target for the treatment of monocytic AML. The receptor LILRB4 on monocytic leukaemia cells suppresses T cell activity and support the infiltration of tumour cells into tissues. [ABSTRACT FROM AUTHOR]

In patients with hematologic malignancies, multiparameter flow cytometry (FCM) offers greater sensitivity than cytology in detecting malignant cells in the initial cerebrospinal fluid (CSF) specimen. However, the role of FCM in assessment of subsequent specimens is unclear. We developed an algorithm to reduce the number of low-yield FCM tests without significant impact on clinically meaningful results. Patients with hematologic malignancies were studied in a derivation cohort, and the following algorithm was developed: (1) cytology and FCM on all initial samples, (2) cytology on all subsequent samples, and (3) FCM on subsequent samples only if previous FCM was positive. A separate population served as the validation cohort. The derivation cohort included 197 patients representing 1157 cytology and 543 FCM samples. Common malignancies were B-Cell ALL (25.3%), diffuse large B cell lymphoma (29.4%), and Burkitt lymphoma (7.7%). In the derivation cohort, the algorithm yielded a sensitivity of 90.0% (95% CI, 81.2-95.6%) and a specificity of 100% (95% CI, 98.9-100.0%). The validation cohort included 132 patients with 563 cytology and 602 FCM samples. In the validation cohort, the testing algorithm yielded a sensitivity of 87.5% (95% CI, 75.9-94.8%) and a specificity of 100% (95% CI, 99.1-100.0%). Of the 15 samples that were missed by the algorithm, FCM findings did not impact patients' management because of known CNS disease (seven patients) or they were responding to treatment (eight patients). CSF testing in hematologic malignancies using the proposed algorithm presents an evidence-based approach to reduce the number of unnecessary FCM tests of CSF without compromising patient care. [ABSTRACT FROM AUTHOR]

Stem-cell fate can be influenced by metabolite levels in culture, but it is not known whether physiological variations in metabolite levels in normal tissues regulate stem-cell function in vivo. Here we describe a metabolomics method for the analysis of rare cell populations isolated directly from tissues and use it to compare mouse haematopoietic stem cells (HSCs) to restricted haematopoietic progenitors. Each haematopoietic cell type had a distinct metabolic signature. Human and mouse HSCs had unusually high levels of ascorbate, which decreased with differentiation. Systemic ascorbate depletion in mice increased HSC frequency and function, in part by reducing the function of Tet2, a dioxygenase tumour suppressor. Ascorbate depletion cooperated with Flt3 internal tandem duplication (Flt3ITD) leukaemic mutations to accelerate leukaemogenesis, through cell-autonomous and possibly non-cell-autonomous mechanisms, in a manner that was reversed by dietary ascorbate. Ascorbate acted cell-autonomously to negatively regulate HSC function and myelopoiesis through Tet2-dependent and Tet2-independent mechanisms. Ascorbate therefore accumulates within HSCs to promote Tet activity in vivo, limiting HSC frequency and suppressing leukaemogenesis. [ABSTRACT FROM AUTHOR]

The Dlk1- Dio3 imprinted domain is located on the cattle chromosome 21 and contains three paternally expressed protein-coding genes and a number of maternally expressed short or long noncoding RNA genes. We have previously obtained two maternally expressed long noncoding RNA genes, Meg8 and Meg9, from the cattle. In this study, we identified a novel noncoding RNA located between Meg8 and Meg9 known as LINC24061 according to the GENCODE annotated bibliography. Two alternatively spliced transcripts ( LINC24061- v1 and LINC24061- v2) were obtained using RT-PCR and RACE, and the expression pattern of LINC24061- v1 and LINC24061- v2 was shown to be tissue-specific. The LINC24061- v1 splice variant was expressed in only three types of tissues: heart, kidney and muscle; in contrast, LINC24061- v2 was expressed in all eight tissues examined, including heart, liver, spleen, lung, kidney, skeletal muscle, subcutaneous fat, and brain of adult cattle. The allele-specific expression of LINC24061 was identified based on a single nucleotide polymorphism (SNP) in exon 2 of LINC24061. The results showed that LINC24061 exhibited monoallelic expression in all the examined cattle tissues. [ABSTRACT FROM AUTHOR]

Sarcoidosis and Crohns disease have been associated with increased long term risk of lymphoproliferative disorders, including lymphomas. Newly developed lymphadenopathy in a patient with these disorders should prompt pathological evaluation. Castleman's disease is a lymphoproliferative disorder characterized by enlarged hyperplastic lymph nodes with regressed follicles surrounded by expanded mantle zones of small lymphocytes, and interfollicular vascular proliferation in the hyaline-vascular type. Similar to sarcoidosis and Crohns disease, its etiology is incompletely understood, although immune dysregulation, genetic factors and infectious and environmental factors are thought to play a role in all three diseases. Interleukin-6 is a possible pathological common factor between these three disease processed. Unicentric, hyaline-vascular type Castleman's disease can be treated successfully with complete surgical resection. We report a patient with long history of sarcoidosis and Crohns disease with newly developed lymphadenopathy which was found to be due to Castleman's disease. [ABSTRACT FROM AUTHOR]

(CaSr)ZrO ceramics were prepared using solid-state reaction process, which were sintered at 1,480 °C for different sintering time (2, 4, 6, 8, 10, 12 h, respectively), their structures were characterized by X-ray diffraction (XRD), scanning electron microscopy, transmission electron microscopy and Raman spectroscopy. Rietveld refinement for the (CaSr)ZrO sintered for 10 h was carried out by powder XRD at room temperature and it crystallizes in orthorhombic space group Pnma [ a = 5.77341(4) Å, b = 8.05569(6) Å, c = 5.63318(4) Å and V = 261.9920(30) Å, Z = 4]. The (CaSr)ZrO ceramics sintered at 1,480 °C for 2-12 h possessed a dielectric constant ( ε) of 23.6-27.9, a quality factor ( Q × f) of 2,160-21,460 GHz and a temperature coefficient of resonant frequency ( τ) from −14 to +13.6 ppm/°C. The Arrhenius plot of the dc electrical conductivity changed significantly with increasing sintering time. [ABSTRACT FROM AUTHOR]

The original article can be found online at https://doi.org/10.1038/s41598-021-04732-4. Correction to: I Scientific Reports i https://doi.org/10.1038/s41598-021-04732-4, published online 18 January 2022 In the original version of this Article, Zhong Yang was omitted as a corresponding author. [Extracted from the article]

The Thermomyces lanuginosus lipase (TLLs) was successfully immobilized within a novel hydrogel matrix through a two-step crosslinking method. TLLs were initially crosslinked through the Schiff base reaction by oxidized carboxymethyl cellulose (OCMC). The water-soluble OCMC@TLLs complex was subsequently crosslinked by carboxymethyl chitosan (CMCSH) in a microfluidic apparatus to form the CMCHS/OCMC@TLLs microspheres. The CD (Circular Dichroism, CD) and FT-IR (Fourier Transform infrared spectroscopy, FT-IR) spectra demonstrated that the crosslinking of TLLs with OCMC resulted in a less significant impact on their structure compared to that with glutaraldehyde. CMCHS/OCMC@TLLs showed decreased catalytic performance due to the mass transfer resistance, while its thermal stability was greatly improved. The CMCHS/OCMC@TLLs were used to catalyze the lauroylation of arbutin in tetrahydrofuran. After 12 h of reaction under optimal conditions, the yield of 6′-O-lauryl arbutin reached an impressive 92.12%. The prepared 6′-O-lauryl arbutin has high lipophilicity and exhibits similar tyrosinase inhibitory activity and higher antioxidant activity compared to its parent compound. [ABSTRACT FROM AUTHOR]

In this way, this issue features twelve selected papers with high quality, aiming at three sections: image based information recognition, image based information processing, and pattern recognition using other kind of information. Mobile Networks and Applications. https://doi.org/10.1007/s11036-021-01905-3 16 Chen X, Zhang X, Zhu M, et al A novel calibration method for tri-axial magnetometers based on an expanded error model and a two-step total least square algorithm. Mobile Networks and Applications. https://doi.org/10.1007/s11036-021-01897-0 7 Bi S, Li X, Ma L, et al Apple internal quality fusion prediction by multi-pattern recognition technology and evidence theory. [Extracted from the article]

The ε4 allele of the APOE gene is thought to increase risk from amnestic mild cognitive impairment (aMCI) to Alzheimer's disease. Cognitive decline in the condition is increasingly considered to worsen functional disconnections in brain network composed of gray matter and white matter. Nevertheless, Whether APOEε4 targets specific white matter functional connectivity in patients with aMCI remains mostly unexplored, mainly due to the challenges of detecting BOLD signals in white matter. Here, we applied a novel approach to investigate APOEε4-related specific bundles and cortical area alterations in aMCI subjects, in order to characterize white matter-gray matter functional connectivity differences throughout the brain. We analyzed 75 patients with aMCI and 76 demographically matched normal controls. The aMCI APOEε4 carriers showed decreased functional connectivity located at left corticospinal tract, bilateral posterior limb of internal capsule, and right temporopolaris, which was different from the regions of aMCI-related changes. We further found that recognition scores were positively associated with the right temporopolaris in aMCI APOEε4 carriers. Collectively, the data provide new evidence that APOEε4 genotype exerts a negative impact on neural activity in both gray and white matter in aMCI, which potentially contributes to functional disconnection and memory decline. A novel method provides full-scale measuring effect of disease conditions on functional architecture throughout the brain. Trial registration: https://www.ClinicalTrials.gov (Identifier: NCT02225964). Registered January 2014. [ABSTRACT FROM AUTHOR]

Background and aims: Artificial liver support systems (ALSS) have been shown to significantly reduce mortality in patients with acute-on-chronic liver failure (ACLF). However, the characteristics of patients who would benefit most from ALSS treatment are poorly understood. This study aimed to delineate the indicators for ALSS and evaluate the effectiveness of plasma perfusion combined with plasma exchange (PP + PE) in patients with hepatitis B virus-related ACLF (HBV-ACLF). Methods: A total of 898 patients with HBV-ACLF in a single center were enrolled retrospectively. Propensity score matching (PSM) was used in case-paired analysis. Hepatic or extra-hepatic organ failures were defined by Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) criteria. Complications included ascites, infection, hepatopulmonary syndrome, hepatorenal syndrome, hepatic encephalopathy and upper gastrointestinal bleeding. Numbers of organ failures or complications were used for risk stratification. Results: Among all patients, 418 patients received standard medical therapy (SMT) and 480 received PP + PE plus SMT. After one-to-one paired PSM within the two groups without risk stratification, 293 pairs were enrolled. The PP + PE group displayed significantly lower mortality risk in both 28- and 90-day observation durations. When stratified, patients with two or more organ failures or complications from the PP + PE group showed greater decrease in mortality risk. Moreover, PP + PE treatment significantly increased the resolution of organ failures and complications and ameliorated the development of new organ failures and complications. Conclusions: PP + PE treatment significantly reversed organ failures and ameliorated the development of new organ failures and complications, thus reducing mortality risk of patients with HBV-ACLF. [ABSTRACT FROM AUTHOR]

Aim: The purpose of this study was to investigate the association of dietary patterns with the risk of insulin resistance (IR), diabetes mellitus (DM), and central obesity in China. Methods: We performed a cross-sectional study on 1432 participants, aged 40–65 years in Hangzhou, Zhejiang province, China. Dietary intake was assessed using a semi-quantitative food frequency questionnaire. Results: Factor analysis extracted four major dietary patterns: vegetable-fruits, rice–meat, seafood–eggs, and sweet–fast. The vegetable-fruits pattern was inversely associated with HOMA-IR (p < 0.001 in both genders), while sweet–fast food pattern was significantly associated with higher HOMA-IR (p = 0.002 in male, and p < 0.001 in female). The vegetables–fruits pattern was inversely correlated with visceral fat area (VFA) (p = 0.029 in males, and p = 0.017 in females), while sweet–fast food pattern presented a significant direct association (p < 0.001 in male) with VFA in males. There was no association observed between the rice–meat pattern or the seafood–eggs pattern and HOMA-IR or VFA. After adjustment for potential confounding factors, participants in the highest tertile of vegetable-fruits pattern showed a significantly lower risk of DM in both males and females (OR: 0.30, 95% CI: 0.13–0.70 in male, and OR: 0.28, 95% CI: 0.11–0.72 in female), and lower risk of central obesity was observed in males (OR: 0.50, 95% CI: 0.29–0.86 in male). Conversely, participants in the highest tertile of sweet–fast food pattern had higher risk of DM (OR: 2.58, 95% CI: 1.23–5.88 in male), and central obesity (OR: 2.85, 95% CI: 1.67–4.86 in male) only in male. While neither the rice–meat pattern nor the seafood–eggs pattern showed significant association with DM or central obesity in both genders. Conclusions: Our findings indicated low risk of IR, DM, and central obesity with vegetable-fruits pattern while inverse relation with sweet–fast food pattern. [ABSTRACT FROM AUTHOR]

Cancer is a complex disease with a fatal outcome. Early detection of cancer, by monitoring appropriate molecular markers is very important for its therapeutic management. In this regard, the short non-coding RNA molecules, microRNAs (miRNAs) have shown great promise due to their availability in circulating fluids facilitating non-invasive detection of cancer. In this study, an in silico comparative analysis was performed to identify specific signature miRNAs dysregulated across multiple carcinomas and simultaneously identify unique miRNAs for each cancer type as well. The miRNA-seq data of cancer patient was obtained from GDC portal and their differential expressions along with the pathways regulated by both common and unique miRNAs were analyzed. Our studies show twelve miRNAs commonly dysregulated across seven different cancer types. Interestingly, four of those miRNAs (hsa-mir-210, hsa-mir-19a, hsa-mir-7 and hsa-mir-3662) are already reported as circulatory miRNAs (circRNAs); while, the miR-183 cluster along with hsa-mir-93 have been found to be incorporated in exosomes signifying the importance of the identified miRNAs for their use as prospective, non-invasive biomarkers. Further, the target mRNAs and pathways regulated by both common and unique miRNAs were analyzed, which interestingly had significant commonality. This suggests that miRNAs that are commonly de-regulated and specifically altered in multiple cancers might regulate similar pathways to promote cancer. Our data is of significance because we not only identify a set of common and unique miRNAs for multiple cancers but also highlight the pathways regulated by them, which might facilitate the development of future non-invasive biomarkers conducive for early detection of cancers. [ABSTRACT FROM AUTHOR]

Collaboration of c-KIT mutations with AML1–ETO (AE) has been demonstrated to induce t(8; 21) acute myeloid leukemia (AML). Targeted therapies designed to eliminate AE and c-KIT oncoproteins may facilitate effective treatment of t(8; 21) AML. Homoharringtonine (HHT) features activity against tumor cells harboring c-KIT mutations, whereas oridonin can induce t(8; 21) AML cell apoptosis and AE cleavage. Therefore, studies should explore the efficacy of combination therapy with oridonin and HHT in t(8; 21) AML. In this study, we investigated the synergistic effects and mechanism of oridonin combined with HHT in t(8; 21) AML cell line and mouse model. The two drugs synergistically inhibited cell viability and induced significant mitochondrial membrane potential loss and apoptosis. Oridonin and HHT induced significant downregulation of c-KIT and its downstream signaling pathways and promoted AE cleavage. HHT increased intracellular oridonin concentration by modulating the expressions of MRP1 and MDR1, thus enhancing the effects of oridonin. The combination of oridonin and HHT prolonged t(8; 21) leukemia mouse survival. In conclusion, oridonin and HHTexert synergistic effects against t(8; 21) leukemia in vivo and in vitro, thereby indicating that their combination may be an effective therapy for t(8; 21) leukemia. [ABSTRACT FROM AUTHOR]

A detailed theoretical study on the thermal decomposition and isomerization of 1-heptyl radical at the CBS-QB3, BH&HLYP, B3PW91, BLYP, MPW1PW91, and M06-2X levels of theory is done. The result shows that the pyrolysis mechanism of 1-heptyl radical mainly includes the isomerization, the C-C, and C-H bond scission reactions. The standard reaction enthalpies for each elementary reaction involved in this system are estimated at several density functional theory methods together with cc-pVDZ basis set and the high-level ab initio CBS-QB3 approach. The theoretical rate coefficients of conventional transition state theory with Eckart tunneling correction (TST/Eckart) for individual elementary reaction involved in the above reaction system are evaluated over the temperature range of 500-2,500 K. The calculated values are in good agreement with available experimental measurements and previous theoretical reports. Furthermore, the isomerization and decomposition reactions are selected to compare their relative importance at different temperatures. It is found that the isomerization process is more pronounced when the temperature is below 1,200 K. Product distribution of 1-heptyl radical pyrolysis is predicted based on the steady-state approximation, and the eventual products are ethylene (CH), propylene (CH), 1-butylene (CH), 1-pentene (CH), and 1-butylethylene (CH). [ABSTRACT FROM AUTHOR]

The ZrO/TiO pillared laponite (Ti-Zr-lap) photocatalysts were prepared with intercalation reaction by supercritical fluid drying (SCFD), and characterized by XRD,TEM, SEM and BET surface area analysis, and the photocatalytic properties of Ti-Zr-lap were investigated by degradation of azo dye acid red B (ARB). The results showed that the ZrO/TiO pillared structures in laponite could be formed, with the mass fraction of (Zr+Ti)/laponite ( X) increasing, the basal spacing and the BET surface area of Ti-Zr-lap significantly increased. The Ti-Zr-lap used as photocatalyst had the advantages of stable and porous layered structure, large surface area with the anatase type TiO. Compared with the Ti-Zr-lap dried by air drying, the Ti-Zr-lap dried by SCFD showed better photocatalytic property which was very close to that of P25 TiO. Using the Ti-Zr-lap as photocatalyst with the optimum X of 0.16 and the calcination temperature of 500 °C, under the conditions of the initial concentration of ARB 20 mg/L, photocatalyst concentration of 1.5 g/L and irradiation time 60 min, the decoloring rate of ARB could achieve 98.3%, indicating that the Ti-Zr-lap had excellent photocatalytic property. [ABSTRACT FROM AUTHOR]