BACKGROUND: Gentiana macrophylla Pall. is a traditional Tibetan medicinal herb possessing antinociceptive and anti-inflammatory activities. Circular RNAs (circRNAs) have been identified to be involved in the tumorigenesis of non-small cell lung cancer (NSCLC). Here, this study focused on investigating the function and mechanism of Gentiana macrophylla flavonoids (GF) and circ_0059665 in NSCLC progression.
METHODS: The contents of mRNA and protein were detected using qRT-PCR and western blotting analysis. Cell proliferative and invasive abilities were evaluated by cell counting kit-8, EdU, colony formation and transwell assays, respectively. M2 macrophage polarization was analyzed by flow cytometry.
RESULTS: GF treatment suppressed NSCLC cell proliferation, invasion and M2 macrophage polarization under hypoxic conditions. Circ_0059665 was highly expressed in NSCLC tissues and cells. Its expression was increased under hypoxic conditions but was reduced following GF treatment. Furthermore, circ_0059665 overexpression reversed the anticancer effects of GF on NSCLC cells under hypoxic conditions. Mechanistically, circ_0059665 acted as a sponge for miR-512-5p to regulate NOVA2 expression. Hypoxia decreased miR-512-5p levels, and increased NOVA2 levels in NSCLC cells, while these tendencies were abolished after GF treatment. Circ_0059665 silencing inhibited NSCLC cell proliferation, invasion and M2 macrophage polarization in hypoxic environments, which were counteracted by NOVA2 overexpression. Moreover, NOVA2 upregulation reversed the suppressive effects of GF on NSCLC cells with hypoxia treatment. In addition, GF impeded NSCLC tumor growth in vivo via suppressing circ_0059665.
CONCLUSIONS: GF treatment in hypoxic environments suppressed NSCLC cell proliferation, invasion and M2 macrophage polarization via the circ_0059665/miR-512-5p/NOVA2 axis.

Recently published work provide the first known evidence of a malignancy-associated regulatory mechanism, functionally connecting a phospho-regulated degron domain embedded in a receptor tyrosine kinase (RTK), with its ectopic expression in cancer, conditional to a specific autocrine growth factor signal. Mechanistically, the growth factor-triggered phosphorylation inhibits the degron domain present in the regulated RTK, blocking access to a specific degradation complex. This ultimately rescues the RTK from rapid ubiquitin-proteasome-system-mediated degradation and, most importantly, causes its cellular overexpression. This mechanism, which has been here assigned the new functional name \"Over-Expression by Degradation Rescue\" (OEDR), provides an additional layer and potentially preferential tool for the control of RTKs expression in cancer, in addition to other mechanisms acting at the transcriptional and messenger transcript stabilization levels. We propose this newly defined phosphorylation/ubiquitination switch-dependent signal to bear wider unexploited relevance in cell biology and human pathophysiology. The recently identified mechanism underlying an OEDR-regulated RTK is discussed herein in the context of physiological endocrine circuits and cancer.

BACKGROUND: Finding a suitable pharmacological substance and a surgical method for improving cartilage graft preparation are necessary. This present study was planned to evaluate the effects of PLGF and graft preparation methods on cartilage graft survival.
METHODS: This controlled, experimental study was performed in Kerman University of Medical Science, Kerman, Iran during 2016- 2017 on two groups of rabbits. Group 1 received PLGF (PLGF +) while Group 2 did not receive any PLGF (PLGF -). In each group, three carilage graft preparation methods including Block Cartilage Graft (BCG), Diced Cartilage Graft (DCG), and Crashed Cartilage Graft (CCG) were used. Three months after the intervention, the grafts were re-assessed and weighed. A specimen from each graft was taken for inflammation, fibrosis, necrosis, and viable chondrocyte.
RESULTS: The CCG method had the maximum ossification percentage (OS%) and no change occurred by PLGF. The BCG method had the greatest viable chondrocyte number, attenuated by PLGF. The BCG method had the highest amount of fibrosis, without any change by PLGF. Additionally, the inflammation percentage and necrosis in the PLGF + group were greater than the PLGF - group.
CONCLUSIONS: The most important effecting factor on the properties of cartilage graft is the method of graft preparation and PLGF only attenuates the methods properties without changing them.

We present Graph Mapping - a simple and effective computerized test of fluid intelligence (reasoning ability). The test requires structure mapping - a key component of the reasoning process. Participants are asked to map a pair of corresponding nodes across two mathematically isomorphic but visually different graphs. The test difficulty can be easily manipulated - the more complex structurally and dissimilar visually the graphs, the higher response error rate. Graph Mapping offers high flexibility in item generation, ranging from trivial to extremally difficult items, supporting progressive item sequences suitable for correlational studies. It also allows multiple item instances (clones) at a fixed difficulty level as well as full item randomization, both particularly suitable for within-subject experimental designs, longitudinal studies, and adaptive testing. The test has short administration times and is unfamiliar to participants, yielding practical advantages. Graph Mapping has excellent psychometric properties: Its convergent validity and reliability is comparable to the three leading traditional fluid reasoning tests. The convenient software allows a researcher to design the optimal test variant for a given study and sample. Graph Mapping can be downloaded from: https://osf.io/wh7zv/.

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The COVID-19 pandemic resulted in more than 4.3 million confirmed cases and more than 2,90,000 deaths worldwide. It has also given rise to fears of an imminent economic crisis and recession. Social distance, self-isolation, and travel restrictions have led to a reduction in the workforce across all economical sectors and have led to a loss of many jobs. Schools have closed down, and the need for commodities and manufactured goods has decreased. On the other hand, the need for medical supplies has increased significantly. The food sector is also facing increased demand as a result of panic buying and storing food products. In response to this global outbreak, we summarize the socioeconomic effects of COVID-19 on the various aspects of the world economy. In Malaysia, the COVID-19 epidemic has checked the resilience of the agriculture sector. Especially the Malaysian paddy industry as country imports 30% of its overall consumption from different parts of the world. The real price of rice triplicating for the consumers, which was alarming for nations in this pandemic situation. The Government of Malaysia introduced the National Agrofood Policy 2011-2020 (NAP4) in 2010 as a guidance document for the implementation of agricultural sector development programs and projects in Malaysia. The NAP4 \'s 10-year term is to be finished by the end of 2020. Several sectors demonstrate substantial success after approximately 8 years of introduction, while the other classes often lag behind the goal and progress quite slowly. Agricultural sector performance is affected by many problems and challenges. In acknowledgment of the poor success of this field, the Ministry of Agriculture and Agri-Based Industry has launched new approaches, policies, and programs that can change the agricultural sector more rapidly. The new direction is aimed at ensuring national food security and boosting farm and revenues. The authorized government agency needs to revise the policy formulation where Malaysia needs to set stages to revolutionize and modernize the rice farming to address the problem faced by the paddy sector in this pandemic situation to adopt GF. In this study, the researcher focuses on the improvisation of the policy to increase the paddy production sustainably.

Ewing sarcoma is a highly aggressive round cell mesenchymal neoplasm, most often occurring in children and young adults. At the molecular level, it is characterized by the presence of recurrent chromosomal translocations. In the last years, next-generation technologies have contributed to a more accurate diagnosis and a refined classification. Moreover, the application of these novel technologies has highlighted the relevance of intertumoral and intratumoral molecular heterogeneity and secondary genetic alterations. Furthermore, they have shown evidence that genomic features can change as the tumor disseminates and are influenced by treatment as well. Similarly, next-generation technologies applied to liquid biopsies will significantly impact patient management by allowing the early detection of relapse and monitoring response to treatment. Finally, the use of these novel technologies has provided data of great value in order to discover new druggable pathways. Thus, this review provides concise updates on the latest progress of these breakthrough technologies, underscoring their importance in the generation of key knowledge, prognosis, and potential treatment of Ewing Sarcoma.

The validity of studies investigating interventions to enhance fluid intelligence (Gf) depends on the adequacy of the Gf measures administered. Such studies have yielded mixed results, with a suggestion that Gf measurement issues may be partly responsible. The purpose of this study was to develop a Gf test battery comprising tests meeting the following criteria: (a) strong construct validity evidence, based on prior research; (b) reliable and sensitive to change; (c) varying in item types and content; (d) producing parallel tests, so that pretest-posttest comparisons could be made; (e) appropriate time limits; (f) unidimensional, to facilitate interpretation; and (g) appropriate in difficulty for a high-ability population, to detect change. A battery comprising letter, number, and figure series and figural matrix item types was developed and evaluated in three large-N studies (N = 3,067, 2,511, and 801, respectively). Items were generated algorithmically on the basis of proven item models from the literature, to achieve high reliability at the targeted difficulty levels. An item response theory approach was used to calibrate the items in the first two studies and to establish conditional reliability targets for the tests and the battery. On the basis of those calibrations, fixed parallel forms were assembled for the third study, using linear programming methods. Analyses showed that the tests and test battery achieved the proposed criteria. We suggest that the battery as constructed is a promising tool for measuring the effectiveness of cognitive enhancement interventions, and that its algorithmic item construction enables tailoring the battery to different difficulty targets, for even wider applications.

Approval of antisense oligonucleotide eteplirsen highlights the promise of exon-skipping therapeutics for Duchenne muscular dystrophy patients. However, the limited efficacy of eteplirsen underscores the importance to improve systemic delivery and efficacy. Recently, we demonstrated that a glucose and fructose (GF) delivery formulation effectively potentiates phosphorodiamidate morpholino oligomer (PMO). Considering the clinical potential of GF, it is important to determine the long-term compatibility and efficacy with PMO in mdx mice prior to clinical translation. Here, we report that yearlong administration of a clinically applicable PMO dose (50 mg/kg/week for 3 weeks followed by 50 mg/kg/month for 11 months) with GF elicited sustainably high levels of dystrophin expression in mdx mice, with up to 45% of the normal level of dystrophin restored in most peripheral muscles without any detectable toxicity. Importantly, PMO-GF resulted in phenotypical rescue and mitochondrial biogenesis with functional improvement. Carbohydrate metabolites measurements revealed improved metabolic and energetic conditions after PMO-GF treatment in mdx mice without metabolic anomaly. Collectively, our study shows PMO-GF\'s ability to elicit long-lasting therapeutic effects with tolerable toxicity and represents a new treatment modality for Duchenne muscular dystrophy, and provides guidelines for antisense oligonucleotides with GF in clinical use.

Understanding the neural and metabolic correlates of fluid intelligence not only aids scientists in characterizing cognitive processes involved in intelligence, but it also offers insight into intervention methods to improve fluid intelligence. Here we use magnetic resonance spectroscopic imaging (MRSI) to measure N-acetyl aspartate (NAA), a biochemical marker of neural energy production and efficiency. We use principal components analysis (PCA) to examine how the distribution of NAA in the frontal and parietal lobes relates to fluid intelligence. We find that a left lateralized frontal-parietal component predicts fluid intelligence, and it does so independently of brain size, another significant predictor of fluid intelligence. These results suggest that the left motor regions play a key role in the visualization and planning necessary for spatial cognition and reasoning, and we discuss these findings in the context of the Parieto-Frontal Integration Theory of intelligence.