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Alternative splicing (AS), a critical post-transcriptional regulatory mechanism, expands gene expression patterns, thereby leading to increased protein diversity. Indeed, more than 95% of human genes undergo alternative splicing events (ASEs). In this study, we drew an all-around AS profile of thyroid cancer cells based on RNA-seq data. In total, there were 45,150 AS in 10,446 thyroid cancer cell genes derived from 506 patients, suggesting that ASEs is a common process in TC. Moreover, 1819 AS signatures were found to be significantly associated with the overall survival (OS) of TC patients. Kaplan–Meier survival analyses suggested that seven types of ASEs were associated with poor prognosis of TC (P < 0.05). Among them, exon skipping (ES) was the most common, with alternate promoter (AP) and alternate terminator (AT) coming second and third, respectively. Our results indicated that acceptor sites (AA) (AUC: 0.937), alternate donor sites (AD) (AUC: 0.965), AT (AUC: 0.964), ES (AUC: 0.999), mutually exclusive exons (ME) (AUC: 0.999), and retained intron (RI) (AUC: 0.837) exhibited an AUC greater than 0.6. In addition, age and risk score (All) were risk factors for TC patients. We also evaluated whether TC-ASEs are regulated by various splicing factors (SFs). We found that the expression of 90 SFs was associated with 469 ASEs and OS of TC patients. Our findings provide an insight into the role of spliceosomes in TC, which may offer novel perspectives in tumor research. [ABSTRACT FROM AUTHOR]

Guanylate binding proteins (GBPs) belongs to the interferons (IFNs) induced guanylate-binding protein family (Guanosine triphosphatases, GTPases) consisting of seven homologous members, termed GBP1 to GBP7. We used multidimensional survey ways to explore GBPs expression, regulation, mutations, immune infiltration and functional networks in head and neck squamous cell carcinoma (HNSCC) patient data based on various open databases. The study provides staggered evidence for the significance of GBPs in HNSCC and its potential role as a novel biomarker. Our results showed that over expressions of 7 GBPs members and multivariate analysis suggested that N-stage, high expressions of GBP1 and low expression of GBP6/7 were linked to shorter OS in HNSCC patients. In addition, B cells of immune infiltrates stimulant the prognosis and might have a medical prognostic significance linked to GBPs in HNSCC. We assume that GBPs play a synergistic role in the viral related HNSCC. Our results show that data mining efficiently reveals information about GBPs expression in HNSCC and more importance lays a foundation for further research on the role of GBPs in cancers. [ABSTRACT FROM AUTHOR]

Empirical kinetic models such as the Monod equation have been widely applied to relate the cell growth with substrate availability. The Monod equation shares a similar form with the mechanistically-based Michaelis-Menten kinetics for enzymatic processes, which has provoked long-standing and un-concluded conjectures on their relationship. In this work, we integrated proteome allocation principles into a Flux Balance Analysis (FBA) model of Escherichia coli, which quantitatively revealed potential mechanisms that underpin the phenomenological Monod parameters: the maximum specific growth rate could be dictated by the abundance of growth-controlling proteome and growth-pertinent proteome cost; more importantly, the Monod constant (Ks) was shown to relate to the Michaelis constant for substrate transport (Km,g), with the link being dependent on the cell's metabolic strategy. Besides, the proposed model was able to predict glucose uptake rate at given external glucose concentration through the size of available proteome resource for substrate transport and its enzymatic cost, while growth rate and acetate overflow were accurately simulated for two E. coli strains. Bridging the enzymatic kinetics of substrate intake and overall growth phenotypes, this work offers a mechanistic interpretation to the empirical Monod law, and demonstrates the potential of coupling local and global cellular constrains in predictive modelling. [ABSTRACT FROM AUTHOR]

Inhibin subunit beta A(INHBA) encodes an individual from the TGF-β superfamily of proteins and the ligand could be further homo-dimerized to shape activin A or hetero-dimerized to frame inhibin with inhibin beta B. We studied INHBA expression, mutations, regulation, function networks and immune infiltrates in data from patients with Head and neck squamous cell carcinoma (HNSCC) based on different open databases by utilizing multi-dimensional investigation techniques. This study gives staggered evidence for the significance of INHBA in head and neck squamous cell carcinoma and its potential role as a novel biomarker. Our outcomes propose that INHBA overexpression in HNSCC has profound impacts in the center hub of post-transcriptional regulation, which is firmly identified with protein translation. Meanwhile, we also examine the function of the identified miRNAs that were related to INHBA and molecular function of these miRNAs were mainly enhanced in transcription factor activity, transcription regulator activity. In addition, B cells of immune infiltrates affecting the prognosis and might have a prognostic significance related to INHBA in HNSCC. Our outcomes show that data mining efficiently uncovers information about INHBA expression in HNSCC and more importance establishing a foundation for further investigation of the role of INHBA in carcinogenesis. [ABSTRACT FROM AUTHOR]

Recently, perinatal outcomes and cumulative live birth rate (CLBR) have widely been utilized to assess the fertility outcomes and safety of assisted reproductive technology (ART), but more robust research is needed to address the success rates of live-healthy births resulting from this procedure, particularly for patients with low prognosis. This study aims to assess and comparative perinatal outcomes and CLBR per cycle of in vitro fertilization/Intracytoplasmic sperm injection (IVF/ICSI) between four groups of low prognosis characterized by POSEIDON criteria. A retrospective assessment was done among infertile women with a low prognosis undergoing IVF/ICSI at a reproductive center in China. Data were collected between January 2011 and December 2015 with a follow-up of at least two years, and censoring was defined by three-cycle completion, discontinuation, or having a live birth. Participants were grouped into 4 groups according to the POSEIDON classification (POSEIDON1, POSEIDON2, POSEIDON3, and POSEIDON4). The main outcomes were perinatal and obstetric outcomes with CLBR per cycle after IVF/ICSI procedure. And IVF/ICSI-technique outcomes as a secondary outcome. Statistical analyses were performed by SPSS, and a p value of < 0.05 was considered significant. A total of 461 eligible participants underwent a total of 825 IVF/ICSI cycles. POSEIDON1 had the best perinatal outcomes in terms of live births (≥ 28w) (54.8%). POSEIDON4 had a higher risk for perinatal and obstetric complications with abortion rate (9.8%); LBW (11.7%), PTD (23.5%), PROM (11.7%), and gestational diabetes (17.6%). POSEIDON2 had a high rate for malpresentation (14.2%), and cesarean delivery(57.2%), while POSEIDON3 was much associated with the occurrences of placenta previa (9.3%) compared to other groups (p value = 0.001). After adjusting odds ratio by age and BMI, POSEIDON4 had the least odds for biochemical pregnancy (p value = 0.019); and the least odds for clinical pregnancy (p value = 0.001) of the four groups. CLBR per cycle was better in POSEIDON1 and increased with an increasing number of cycles in all groups during the three cycles. Conservative CLBR after three complete cycles were 77.27%, 42.52%, 51.4% and 22.34%, while optimistic CLBR were 79.01%, 51.19%, 58.59% and 34.46% in POSEIDON1 to POSEIDON4, respectively. Younger women with low prognosis and normal ovarian reserve have a higher probability for live births and better perinatal outcomes compared with older women with poor or normal ovarian reserve. Besides, young women with low prognosis, despite ovarian reserve status, can increase their probability of conception and get relatively higher CLBR by undergoing multiple cycles of IVF/ICSI. Age is therefore considered as a critical parameter in predicting the perinatal outcome and CLBR. [ABSTRACT FROM AUTHOR]

Mutant RAS genes play an important role in regulating tumors through lysine residue 104 to impair GEF-induced nucleotide exchange, but the regulatory role of KRAS K104 modification on the KRASG12D mutant remains unclear. Therefore, we simulated the acetylation site on the KRASG12D three-dimensional protein structure, including KRASG12D, KRASG12D/K104A and KRASG12D/K104Q, and determined their trajectories and binding free energy with GEF. KRASG12D/K104Q induced structural changes in the α2- and α3-helices, promoted KRAS instability and hampered GEF binding (ΔΔG = 6.14 kJ/mol). We found decreased binding to the Raf1 RBD by KRASG12D/K104Q and reduced cell growth, invasion and migration. Based on whole-genome cDNA microarray analysis, KRASG12D/K104Q decreased expression of NPIPA2, DUSP1 and IL6 in lung and ovarian cancer cells. This study reports computational and experimental analyses of Lys104 of KRASG12D and GEF, and the findings provide a target for exploration for future treatment. [ABSTRACT FROM AUTHOR]

Recently, metal phosphides have been investigated as potential anode materials because of higher specific capacity compared with those of carbonaceous materials. However, the rapid capacity fade upon cycling leads to poor durability and short cycle life, which cannot meet the need of lithium-ion batteries with high energy density. Herein, we report a layer-structured GeP3/C nanocomposite anode material with high performance prepared by a facial and large-scale ball milling method via in-situ mechanical reaction. The P-O-C bonds are formed in the composite, leading to close contact between GeP3 and carbon. As a result, the GeP3/C anode displays excellent lithium storage performance with a high reversible capacity up to 1109 mA h g−1 after 130 cycles at a current density of 0.1 A g−1. Even at high current densities of 2 and 5 A g−1, the reversible capacities are still as high as 590 and 425 mA h g−1, respectively. This suggests that the GeP3/C composite is promising to achieve high-energy lithium-ion batteries and the mechanical milling is an efficient method to fabricate such composite electrode materials especially for large-scale application. [ABSTRACT FROM AUTHOR]