Re-wiring and gene expression changes of AC025034.1 and ATP2B1 play complex roles in early-to-late breast cancer progression

Background Elucidating the dynamic topological changes across different stages of breast cancer, called stage re-wiring, could lead to identifying key latent regulatory signatures involved in cancer progression. Such dynamic regulators and their functions are mostly unknown. Here, we reconstructed differential co-expression networks for four stages of breast cancer to assess the dynamic patterns of cancer progression. A new computational approach was applied to identify stage-specific subnetworks for each stage. Next, prognostic traits of genes and the efficiency of stage-related groups were evaluated and validated, using the Log-Rank test, SVM classifier, and sample clustering. Furthermore, by conducting the stepwise VIF-feature selection method, a Cox-PH model was developed to predict patients’ risk. Finally, the re-wiring network for prognostic signatures was reconstructed and assessed across stages to detect gain/loss, positive/negative interactions as well as rewired-hub nodes contributing to dynamic cancer progression. Results After having implemented our new approach, we could identify four stage-specific core biological pathways. We could also detect an essential non-coding RNA, AC025034.1, which is not the only antisense to ATP2B1 (cell proliferation regulator), but also revealed a statistically significant stage-descending pattern; Moreover, AC025034.1 revealed both a dynamic topological pattern across stages and prognostic trait. We also identified a high-performance Overall-Survival-Risk model, including 12 re-wired genes to predict patients’ risk (c-index = 0.89). Finally, breast cancer-specific prognostic biomarkers of LINC01612, AC092142.1, and AC008969.1 were identified. Conclusions In summary new scoring method highlighted stage-specific core pathways for early-to-late progressions. Moreover, detecting the significant re-wired hub nodes indicated stage-associated traits, which reflects the importance of such regulators from different perspectives.

Exposure of thermoplastics to methanol–gasoline blends: A material compatibility study

Alcohols are increasingly being looked upon as the most viable alternative to the conventional sources of energy. Methanol is the first member of the alcohol family and can be easily synthesized from syngas. It is an attractive blend to gasoline due to its advantageous properties. There is a necessity to make sure that the infrastructure is ready to adapt these alternative fuels. Hence, the aim of this study is to assess the degradation of widely used thermoplastics in fuel tanks, pipes, and the fuel injection system, namely, polytetrafluoroethylene (PTFE), polyethyleneterephthalate (PET), and high density polyethylene (HDPE) post exposure to methanol–gasoline blends (P100, M15, and M30) for a period of 4, 10, and 30 days. The effects of the exposure were examined by comparing changes in gain/loss of mass, hardness, elongation, and tensile strength. The surface morphology changes of the polymeric coupons were characterized by scanning electron microscopy and their elemental analysis was done by energy dispersive X-ray spectroscopy. The studied materials were found to gain mass in the order HDPE > PTFE >PET. The decrease in hardness was found to be more in HDPE followed by PTFE and PET. PTFE and PET showed reduction in strength but an increase in tensile strength was observed for HDPE post exposure to fuel blend. Highest change in elongation was found in HDPE followed by PTFE and PET. The changes were found to be the least in P100 followed by M15 and maximum in M30 blends for all immersion periods.

An investigation of PT -symmetry breaking in tight-binding chains

We consider non-Hermitian PT -symmetric tight-binding chains where gain/loss optical potentials of equal magnitudes ±iγ are arbitrarily distributed over all sites. The main focus is on the threshold γ c beyond which PT -symmetry is broken. This threshold generically falls off as a power of the chain length, whose exponent depends on the configuration of optical potentials, ranging between 1 (for balanced periodic chains) and 2 (for unbalanced periodic chains, where each half of the chain experiences a non-zero mean potential). For random sequences of optical potentials with zero average and finite variance, the threshold is itself a random variable, whose mean value decays with exponent 3/2 and whose fluctuations have a universal distribution. The chains yielding the most robust PT -symmetric phase, i.e. the highest threshold at fixed chain length, are obtained by exact enumeration up to 48 sites. This optimal threshold exhibits an irregular dependence on the chain length, presumably decaying asymptotically with exponent 1, up to logarithmic corrections.

ZC3H13 Inhibits the Progression of Hepatocellular Carcinoma through m6A-PKM2-Mediated Glycolysis and Enhances Chemosensitivity

Objective. N6-Methyladenosine (m6A) is the most prevalent RNA epigenetic modulation in eukaryotic cells, which serves a critical role in diverse physiological processes. Emerging evidences indicate the prognostic significance of m6A regulator ZC3H13 in hepatocellular carcinoma (HCC). Herein, this study was conducted for revealing biological functions and mechanisms of ZC3H13 in HCC. Methods. Expression of ZC3H13 was examined in collected HCC and normal tissues, and its prognostic significance was investigated in a public database. Gain/loss of functional assays were presented for defining the roles of ZC3H13 in HCC progression. The specific interactions of ZC3H13 with PKM2 were validated in HCC cells via mRNA stability, RNA immunoprecipitation, and luciferase reporter and MeRIP‐qPCR assays. Moreover, rescue experiments were carried out for uncovering the mechanisms. Results. ZC3H13 expression was downregulated in HCC, and its loss was in relation to dismal survival outcomes. Functionally, overexpressed ZC3H13 suppressed proliferation, migration, and invasion and elevated apoptotic levels of HCC cells. Moreover, ZC3H13 overexpression sensitized to cisplatin and weakened metabolism reprogramming of HCC cells. Mechanically, ZC3H13-induced m6A modified patterns substantially abolished PKM2 mRNA stability. ZC3H13 facilitated malignant behaviors of HCC cells through PKM2-dependent glycolytic signaling. Conclusion. Collectively, ZC3H13 suppressed the progression of HCC through m6A-PKM2-mediated glycolysis and sensitized HCC cells to cisplatin, which offered a fresh insight into HCC therapy.

Downregulated Expression of miRNA-130a-5p Aggravates Hepatoma Progression via Targeting PTP4A2

Background. Hepatoma is a leading cause of death worldwide, with high metastasis and recurrence rates. The aberrant expression of miRNA-130a-5p is involved in the development and progression of various cancers. However, there are no studies investigating the role of miRNA-130a-5p in hepatoma. The present study is aimed at clarifying the functional role of miRNA-130a-5p in hepatoma progression. Methods. The expression levels of miRNA-130a-5p in hepatoma tissues and cell lines were detected by qRT-PCR assays. Bioinformatic analysis, gain-/loss-of-function experiments, and luciferase activity assays were conducted to verify whether miRNA-130a-5p is targeted by protein tyrosine phosphatase 4A2 (PTP4A2). The functions of miRNA-130a-5p and PTP4A2 in hepatoma were determined by cell proliferation assays. Results. The expression of miRNA-130a-5p was downregulated in hepatoma tissues and was related to poor prognosis. However, the expression level of PTP4A2 was contradictory to that of miRNA-130a-5p, and PTP4A2 upregulation could aggravate hepatoma progression. The ectopic overexpression of PTP4A2 promoted hepatoma cell proliferation in vitro, which could be reversed by miRNA-130a-5p. Conclusions. Our study implies that miRNA-130a-5p, which is downregulated in hepatoma tissues, can suppress hepatoma cell proliferation via targeting PTP4A2.

Retrospective Analysis of INRG Clinical and Genomic Factors for 605 Neuroblastomas in Japan: A Report from the Japan Children’s Cancer Group Neuroblastoma Committee (JCCG-JNBSG)

Neuroblastomas (NBs) exhibit broad and divergent clinical behaviors and tumor risk classification at diagnosis is crucial for the selection of an appropriate therapeutic strategy for each patient. The present study aimed to validate the clinical relevance of International Neuroblastoma Risk Group (INRG) prognostic and genomic markers in a Japanese NB cohort using a retrospective analysis. Follow-up data based on 30 common INRG queries in 605 NB cases diagnosed in Japan between 1990 and 2014 were collected and the genome signature of each tumor sample was integrated. As previously indicated, age, tumor stage, MYCN, DNA ploidy, the adrenals as the primary tumor site, serum ferritin and lactate dehydrogenase (LDH) levels, segmental chromosome aberrations, and the number of chromosome breakpoints (BP) correlated with lower survival rates, while the thorax as the primary tumor site and numerical chromosome aberrations correlated with a favorable prognosis. In the patient group with stage 4, MYCN non-amplified tumors (n = 225), one of the challenging subsets for risk stratification, age ≥ 18 months, LDH ≥ 1400 U/L, and BP ≥ 7 correlated with lower overall and event-free survival rates (p < 0.05). The genome subgroup GG-P2s (partial chromosome gain/loss type with 1p/11q losses and 17q gain, n = 30) was strongly associated with a lower overall survival rate (5-year survival rate: 34%, p < 0.05). Therefore, the combination of the tumor genomic pattern (GG-P2s and BP ≥ 7) with age at diagnosis and LDH will be a promising predictor for MYCN-non-amplified high-risk NBs in patient subsets, in accordance with previous findings from the INRG project.

Comparative Genomics and Gene Pool Analysis Reveal the Decrease of Genome Diversity and Gene Number in Rice Blast Fungi by Stable Adaption with Rice

Magnaporthe oryzae caused huge losses in rice and wheat production worldwide. Comparing to long-term co-evolution history with rice, wheat-infecting isolates were new-emerging. To reveal the genetic differences between rice and wheat blast on global genomic scale, 109 whole-genome sequences of M. oryzae from rice, wheat, and other hosts were reanalyzed in this study. We found that the rice lineage had gone through stronger selective sweep and fewer conserved genes than those of Triticum and Lolium lineages, which indicated that rice blast fungi adapted to rice by gene loss and rapid evolution of specific loci. Furthermore, 228 genes associated with host adaptation of M. oryzae were found by presence/absence variation (PAV) analyses. The functional annotation of these genes found that the fine turning of genes gain/loss involved with transport and transcription factor, thiol metabolism, and nucleotide metabolism respectively are major mechanisms for rice adaption. This result implies that genetic base of specific host plant may lead to gene gain/loss variation of pathogens, so as to enhance their adaptability to host. Further characterization of these specific loci and their roles in adaption and evaluation of the fungi may eventually lead to understanding of interaction mechanism and develop new strategies of the disease management.

Vocational and Educational Attitudes of Young People in the Context of the Migration Outflow of the Population of the Arctic Territories (on the Example of the Murmansk Oblast)

The article deals with the peculiarities of the regional context of socialization of the youth of the subjects of the AZRF in the field of implementation of vocational and educational attitudes. The paper presents a summary analysis of statistical indicators of migration gain (loss) in the AZRF, including the structure by age groups, as well as data on the dynamics of the number of students studying at different types of ed-ucational institutions from 2005 to 2020. Statistical indicators of migration gain (loss) have revealed a trend of a sharp decrease in the outflow of population in the Russian Arctic. The obvious reasons for this situation were the consequences of the COVID-19 pandemic, which significantly increased the changes in the logic of the reproduction of the social structures, in particular, there was a migration turn towards provincial subjects, as the most favorable for life, in contrast to megacities and large cities. It actualizes and problematizes the possibilities of the environment of remote regions for the optimal socialization of young people. The authors of the article focus on environmental factors that contribute to the formation and implementation of professional and educational attitudes of young people in the region. The purpose of the article is to study the professional and educational attitudes of young people in the conditions of the migration outflow of the population. The object of the research is young people studying in the Murmansk Oblast. The choice of a specific subject of the Russian Arctic (Murmansk Oblast) is due to a number of reasons: intensive migration loss of population; significant reduction in the number of educational institutions; reduction in the number of students in comparison with other subjects of the Russian Arctic. The empirical basis of the article was formed by the results of a sociological study conducted in April–May 2021 in the Murmansk Oblast using the online survey method among graduates of educational institutions of secondary general (523 people), secondary vocational (519 people) and higher education (bachelor level) (283 people).

Measuring happiness under interpersonal comparison: An advanced theoretical framework and implications

The origin of happiness arouses people’s curiosity for a long time. Recent research introduces a utility theory for measuring subjective happiness in a social context. The past recent monetary conditions influence the present subjective happiness through two distinct channels: interpersonal comparison and self-adaptation. In this paper, we develop this theory to analyze behavioral patterns. Together with prospect theory’s gain-loss utility function, we exploit the theory in predicting psychological phenomena of craving. We explore the relationships between happiness and earnings. Under certain conditions, a high payoff disappoints you immediately and even leads to continuous disappointment across periods. We extend the explanations of the scenarios of New York cabdrivers’ labor-supply decisions. The effect of social comparisons may trigger workers’ behaviors of quit-working, which deepen related understandings of the literature.