Hidradenitis suppurativa (HS) is a chronic inflammatory disease that is difficult to control, and its mechanism remains unclear. Hepatocyte GF (HGF) has been reported to be significantly upregulated in the serum and skin of patients with HS, especially in the lesions with tunnels. In this study, we examined the transcriptome of HGF-treated keratinocytes and compared it with genetic profiling of HS lesions. HGF was highly expressed in HS skin, especially in the deep dermis, compared with that in healthy controls, and its source was mainly fibroblasts. HGF upregulated more genes in keratinocytes than IL-17A or TNF-a, and these genes included multiple epithelial-mesenchymal transition-related genes. Differentially expressed genes in HGF-stimulated keratinocytes were involved in activation of epithelial-mesenchymal transition-related pathways. These HGF-induced genes were significantly upregulated in HS lesions compared with those in healthy skin and nonlesions and were more strongly associated with HS tunnels. In summary, HGF was highly expressed in HS and induced epithelial-mesenchymal transition-related genes in keratinocytes; HGF-induced genes were highly associated with gene profiling of HS with tunnels, suggesting that HGF may be involved in HS tunnel formation through epithelial-mesenchymal transition.

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: Shenfu decoction (SFD) is a classic Chinese medicine prescription that has a strong cardiotonic effect. The combination of ginseng (the dried root of Panax ginseng C. A. Meyer) and Fuzi (processed product of sub-root of Aconitum carmichaeli Debx), the main constituents of SFD, has been reported to improve the pharmacological effect of each other. Moreover, research has shown that the main active components of SFD, ginseng total saponins (GTS) and Fuzi total alkaloids (FTA), have antidepressant activity. However, the effects of these ingredients on depressive-like behavior induced by ovariectomy, a model of menopausal depression, have not been studied.
OBJECTIVE: Our research aims to elucidate the antidepressant-like effects of GTS and FTA compatibility (GF) in ovariectomized mice and the potential mechanisms.
METHODS: To elucidate the antidepressant-like effects of GF in mice in ovariectomy condition, behavioral tests were performed after 7 days of intragastric administration of different doses of GF. Underlying molecular mechanisms of CREB-BDNF, BDNF-mTORC1 and autophagy signaling were detected by western blotting, serum metabolites were examined by UPLC-QE plus-MS and dendritic spine density was determined by Golgi-Cox staining.
RESULTS: GF remarkably decreased the immobility time in the forced swim test. GF also increased levels of pCREB/CREB, BDNF, Akt, mTORC1 and p62 in the prefrontal cortex and hippocampus, as well as decreased LC3-II/LC3-I in the prefrontal cortex and hippocampus of ovariectomized mice. Furthermore, 15 serum differential metabolites (9 of which are lipids and lipid molecules) were identified by metabonomics. Next, the antidepressant-like effects of GF was blocked by rapamycin, an inhibitor of mTORC1. The antidepressant actions of GF on levels of pCREB, mTORC1, LC3-Ⅱ/LC3-Ⅰ and p62 in the prefrontal cortex and the levels of BDNF, Akt, mTORC1 and p62 in the hippocampus were inhibited by rapamycin, and the dendritic spines density was also regulated.
CONCLUSIONS: GF has antidepressant effects in ovariectomized mice, and like other antidepressants, these effects involve activation of BDNF-mTORC1, autophagy regulation and consequent effects on hippocampal synaptic plasticity. Moreover, metabolomic results suggest that GF also has effects on peripheral lipid profiles that may provide potential biomarkers for these antidepressant-like effects. These results indicate that GF is worthy of further exploration as a promising pharmaceutical treatment for depression. This study provides a new direction for the development of new indications for traditional Chinese medicine compounds.

In proliferating cells and tissues a number of checkpoints (G1/S and G2/M) preceding cell division (M-phase) require the signal provided by growth factors present in serum. IGFs (I and II) have been demonstrated to constitute key intrinsic components of the peptidic active fraction of mammalian serum. In vivo genetic ablation studies have shown that the cellular signal triggered by the IGFs through their cellular receptors represents a non-replaceable requirement for cell growth and cell cycle progression. Retroactive and current evaluation of published literature sheds light on the intracellular circuitry activated by these factors providing us with a better picture of the pleiotropic mechanistic actions by which IGFs regulate both cell size and mitogenesis under developmental growth as well as in malignant proliferation. The present work aims to summarize the cumulative knowledge learned from the IGF ligands/receptors and their intracellular signaling transducers towards control of cell size and cell-cycle with particular focus to their actionable circuits in human cancer. Furthermore, we bring novel perspectives on key functional discriminants of the IGF growth-mitogenic pathway allowing re-evaluation on some of its signal components based upon established evidences.

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.