Opposite Roles Research Articles

Cryo-EM structure of histidyl-tRNA synthetase-like domain reveals activating crossed helices at the core of GCN2.

GCN2 is a conserved receptor kinase activating the integrated stress response (ISR) in eukaryotic cells. The ISR kinases detect accumulation of stress molecules and reprogram translation from basal tasks to preferred production of cytoprotective proteins. GCN2 stands out evolutionarily among all protein kinases due to the presence of a histidyl-tRNA synthetase-like (HRSL) domain, which arises only in GCN2 and is located next to the kinase domain (KD). How HRSL contributes to GCN2 signaling remains unknown. Here, we report a 3.2 Å cryo-EM structure of HRSL from thermotolerant yeast Kluyveromyces marxianus. This structure shows a constitutive symmetrical homodimer featuring a compact helical-bundle structure at the junction between HRSL and KDs, in the core of the receptor. Mutagenesis demonstrates that this junction structure activates GCN2 and indicates that our cryo-EM structure captures the active signaling state of HRSL. Based on these results, we put forward a GCN2 regulation mechanism, where HRSL drives the formation of activated kinase dimers. The remaining domains of GCN2 have the opposite role and in the absence of stress they help keep GCN2 basally inactive. This auto-inhibitory activity is relieved upon stress ligand binding. We propose that the opposing action of HRSL and additional GCN2 domains thus yields a regulated ISR receptor.

Competitive binding of small antagonistic peptides to the OsER1 receptor optimizes rice panicle architecture.

Rice panicle architecture is a pivotal trait that strongly contributes to grain yield. Small peptide ligands from the OsEPF/EPFL family synergistically control panicle architecture by recognition of the OsER1 receptor and subsequent activation of the OsMKKK10-OsMKK4-OsMPK6 cascade, indicating that specific ligand-receptor pairs orchestrate rice panicle development. However, how small homologous peptides fine-tune organ morphogenesis by targeting a common receptor remains elusive. Here, we report that the small peptide OsEPFL5 acts as a ligand of the OsER1 receptor that inactivates the OsMKKK10-OsMKK4-OsMPK6 cascade, suggesting that OsEPFL5 plays the opposite role to that of the OsEPFL6/7/8/9 subfamily in regulating spikelet number per panicle and grain size. Notably, OsEPFL5 competitively replaces the OsEPFL6, OsEPFL7, OsEPFL8, or OsEPFL9 binding to the OsER1 receptor, exposing antagonistic competition between small homologous peptides. Specifically enhancing expression of OsEPFL5 significantly improves grain yield by suppressing functions of the ligand-receptor pairs of OsEPFL6-OsER1, OsEPFL7-OsER1, OsEPFL8-OsER1, and OsEPFL9-OsER1, suggesting that competitive binding to the OsER1 receptor by small antagonistic peptides can optimize rice panicle architecture. Our findings elucidate how a receptor agonist and antagonist define inductive and inhibitory cues to shape rice panicle architecture, thus providing a new method of rationally breaking yield trait coupling by manipulating small antagonistic peptides.

The opposite roles of injustice and cruelty in the internalization of a devaluation: The humiliation paradox revisited.

Cruelty and its link to injustice in contexts of humiliation have not received to date due attention from experimental psychosocial research. Aiming at filling this gap, this paper presents three studies with increasing degrees of experimental control (Ntotal = 1098) that show a dual opponent-process response to being targeted by potentially humiliating actions: while targets appraising more injustice internalize less the devaluation underlying the humiliation experience (thus partially dissolving the so-called "paradox of humiliation", Fernández etal., 2015, Personality and Social Psychology Bulletin, 41, 976), targets appraising more cruelty internalize more a devalued self-view and feel more humiliated. The fine balance between these two closely connected but distinct appraisals is key to understand the internal/subjective experience of targets: seeing themselves mainly as victims of injustice or cruelty will prevent or favour, respectively, their internalization of the devaluation and their feeling humiliated. This opposite pattern also impacts victims' reaction: Both appraisals relate to aggressive responses via anger but while appraising cruelty also paradoxically leads to powerless inertia, appraising injustice (including importantly the injustice of cruelty itself) leads to less powerlessness and more assertive agency. The theoretical and applied implications of approaching the victims of humiliation as victims of both an injustice and a cruelty are discussed.

Gendered experience of military service in the Armed Forces of Ukraine (on the example of a military unit X 0000)

Over the past 10 years, the Ukrainian state has provided opportunities for women to serve in the army on an equal basis with men at the legislative level. Meanwhile, the army may still be identified as a maledominated institution, as Ukrainian servicewomen still face challenges during their service because of their sex.The empirical frame of the study was a case study (containing qualitative and quantitative components) of the experience of military service in the military unit X 0000. Based on the analysis of secondary sources and our own empirical research, we managed to identify gendered challenges specific to the experience of servicewomen in the Armed Forces, including during the Russian-Ukrainian war.The key gendered challenges of serving in the military unit X 0000 for women were vertical and horizontal gender segregation; the need to correspond with masculine standards and to combine the status of a military with the status of a woman, wife, and mother that sometimes have opposite role expectations, which can lead to role conflict; the need to combine childcare and household duties with work; stereotypes about servicewomen that exist within and outside the army; sexism and violence (psychological abuse and sexual harassment). The case study results allowed us to confirm empirically, illustrate with examples, and clarify the range of gendered challenges in the army, outlined in the analysis of secondary sources.The study highlights the special challenges for military women that arise during the period of Russia’s full-scale invasion of Ukraine. For example, women, unlike men, may be protected and prevented from working in ‘male’ positions. The article also shows that servicewomen may themselves uphold traditional gender roles, try to conform to patriarchal norms, and oppose gender equality. All this leads to the reproduction of gender inequality in the army.

Artificial selection of two antagonistic E3 ubiquitin ligases finetunes soybean photoperiod adaptation and grain yield

The precise control of flowering time is of utmost importance for crop adaptation to varying environmental conditions and consequently determines grain yield and plant fitness. Soybean E2, the homolog of Arabidopsis GIGANTEA, is a major locus contributing to high-latitude adaptation and is involved in photoperiod sensitivity. However, due to major effects of E2, additional genetic loci controlling soybean flowering and adaptation have historically been masked and difficult to identify. Here, by eliminating the effect of E2, we identified a Tof9 locus controlling flowering in which ZEITLUPE 2 (ZTL2) is the causal gene. ZTL2 encodes an F-box E3 ubiquitin ligase with homology to Arabidopsis ZEITLUPE and is shown to play a key role in the soybean photoperiodic flowering pathway. ZTL2 physically interacts with E2 to mediate its degradation. Intriguingly, ZTL2 and FKF1, both belong to the F-box-type E3 ubiquitin-ligase family, exhibit opposite roles in regulating soybean flowering. ZTL2 degrades E2, leading to early flowering, while FKF1 stabilizes E2, resulting in delayed flowering. The balance between ZTL2-mediated degradation and FKF1-mediated stabilization enables soybeans to finetune flowering time and maximize grain yield. Field-grown ztl2 mutants are taller, flower late, and have increased yield parameters. ZTL2 and FKF1b bear contrasting artificial-selection patterns to adapt to different latitudes. This antagonistic regulation is crucial for soybean adaptation to diverse ecological settings and allows plants to fine-tune their flowering time in response to photoperiod and latitudinal changes.

Influence of couple stress, radiation, and activation energy on MHD flow and entropy generation in Maxwell hybrid nanofluid flow over a flat plate

Countless engineering applications rely on heat and mass transportation technologies. Limitations in thermal conductivity and mass diffusivity are common in conventional fluids. Nanofluids, which are essentially base fluids with nanoparticles suspended in them, have superior thermal characteristics than base fluids without the nanoparticles. Maxwell hybrid nanofluids have the potential to improve mass and heat transport even further by combining the characteristics of two different types of nanoparticles. The magnetohydrodynamic (MHD) flow and heat transmission properties of a Maxwell hybrid nanofluid through a flat plate are investigated in this work. The novelty of this research lies in its exploration of the combined impressions of couple stress and activation energy on the flow behaviour. The equations governing the problem undergo transformation and are handled by means of the bvp4c solver. The vital discoveries disclose that the nanoparticle concentration and magnetic field strength act as opposing forces to fluid velocity. And also, it is detected that the friction coefficient rises by 2.68% as the value of volume fraction of copper nanoparticles ranges from 0 to 0.105. It is found that there is a decrement of 29.7% in the heat transmission rate when the values of Eckert number lie between 0 and 0.6. It is observed that the reaction rate and activation energy parameters play opposite roles against fluid concentration. It is discovered that the entropy generation increases with factors that enhance friction and heat dissipation (Maxwell and Brinkman parameters). The results show that the Sherwood number drops 4.4% when the activation energy parameter is set to values between 0 and 3.

The Synergistic and Opposing Roles of ω-Fatty Acid Hydroxylase (CYP4A11) and ω-1 Fatty Acid Hydroxylase (CYP2E1) in Chronic Liver Disease

Cytochrome P450 fatty acid hydroxylase consists of members of the CYP4 family that ω-hydroxylate fatty acids and the CYP2E1 that ω-1 hydroxylates fatty acids. Although ω and ω-1 hydroxylation of fatty acids have been thought to play a minor role in fatty acid metabolism (less than 20%), it plays a vital role in excess liver fatty acids overload seen in fasting, diabetes, metabolic disorder, and over-consumption of alcohol and high-fat diet. This pathway provides anabolic metabolites for gluconeogenesis, succinate, and acetate for lipogenesis. The CYP4A and CYP2E1 genes are activated in fasting and several metabolic disorders, suggesting a synergistic role in preventing fatty acid-induced lipotoxicity with the consequence of increased liver cholesterol and lipogenesis leading to increased Lipid Droplet (LD) deposition. During the progression of Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD), activation of Phospholipase A2 (PLA2) releases arachidonic acid that CYP4A11 and CYP2E1 P450s metabolize to produce 20-hydroxyeicosatetraenoic acid (20-HETE) and 19-HETE, respectively. These metabolites have opposing roles in the progression of MASLD and chronic liver disease (CLD). This report discusses the synergistic role of the CYP4A and CYP2E1 P450s in the metabolism of saturated and unsaturated fatty acids and their opposite physiological role in the metabolism of Arachidonic Acid (AA). We finally discuss the role of ethanol in disrupting the synergistic and opposing roles of the CYP4A and CYP2E1 genes in MASLD and CLD.

Internal radiation effect on semiconductor β-Ga2O3 crystals grown by the VB Method and anisotropic thermal stress

Gallium oxide crystals are semitransparent semiconductors with good optical and electrical properties, which allow their use for several technological applications. During the growth process of β-Ga2O3 crystals, internal radiation plays a crucial role that affects the growth process and then the crystal quality. In this work, the effect of the melt and the crystal transparency on the vertical Bridgman growth of β-Ga2O3 oxide is thoroughly studied. Using a global 2D/3D finite element model, temperature, melt flow, melt-crystal interface, and three-dimensional anisotropic thermal stress are computed at different growth stages. At each stage, four cases are considered, namely, opaque melt and crystal, semi-transparent melt and opaque crystal, semitransparent crystal and opaque melt, and finally semitransparent melt and crystal. The role of internal radiation in each case at different growth stages is then highlighted separately and then coupled together. It was found that the melt-crystal interface is shifted from a convex shape at the early stage to a nearly plane and then to a concave shape at the last stage. The melt flow is then changed from two rolls pattern at the beginning to a single-roll structure at the last stage. Thermal stress of the as-grown ingot is decreased during the growth due to the decrease of temperature non-linearities. Internal radiation inside the crystal acts to increase the melt-crystal interface convexity at the early and middle stages of the growth process and leads to a decrease in its concavity at the final stage. However, the melt transparency leads to the opposite effects, i.e., it decreases the interface convexity at the early stage and increases the interface concavity at the final stage. As a result, for semitransparent crystal and melt, the interface is between the two previous cases. The calculated thermal stresses are found to be more affected by the transparency of the crystal than the melt as the absorption coefficient of β-Ga2O3 crystal is smaller than that of the melt. At all stages, the thermal stresses are found to be larger for the opaque case due to the increase of temperature non-linearities in the crystal. Large values are found at the bottom and the lower part of the periphery. Furthermore, internal radiation inside the melt plays a major role during the early growth stage due to the large liquid volume. It reduces the melt flow intensity close to the free surface where the shear stress is combined with the buoyant force and leads to the flattening of the interface decreasing then the radial temperature gradients, which leads to small attenuation of the thermal stress. At the final stage, the transparency of the melt plays the opposite role due to the increase of the interface concavity which leads to an increase in both of the temperature gradients and the thermal stress inside the crystal. Due to the crystal anisotropy, and especially to the large thermal expansion coefficient in the [010] direction, the 3D thermal stress values are found to be larger in this direction, especially in the bottom part of the ingot. Comparisons with available experimental and numerical works are provided in this paper.

Antagonistic roles of tau and MAP6 in regulating neuronal development.

Association of tau (encoded by Mapt) with microtubules causes them to be labile, whereas association of MAP6 with microtubules causes them to be stable. As axons differentiate and grow, tau and MAP6 segregate from one another on individual microtubules, resulting in the formation of stable and labile domains. The functional significance of the yin-yang relationship between tau and MAP6 remains speculative, with one idea being that such a relationship assists in balancing morphological stability with plasticity. Here, using primary rodent neuronal cultures, we show that tau depletion has opposite effects compared to MAP6 depletion on the rate of neuronal development, the efficiency of growth cone turning, and the number of neuronal processes and axonal branches. Opposite effects to those seen with tau depletion were also observed on the rate of neuronal migration, in an in vivo assay, when MAP6 was depleted. When tau and MAP6 were depleted together from neuronal cultures, the morphological phenotypes negated one another. Although tau and MAP6 are multifunctional proteins, our results suggest that the observed effects on neuronal development are likely due to their opposite roles in regulating microtubule stability.

Myoblast-Derived Galectin 3 Impairs the Early Phases of Osteogenesis Affecting Notch and Akt Activity.

Galectin-3 (Gal-3) is a pleiotropic lectin produced by most cell types, which regulates multiple cellular processes in various tissues. In bone, depending on its cellular localization, Gal-3 has a dual and opposite role. If, on the one hand, intracellular Gal-3 promotes bone formation, on the other, its circulating form affects bone remodeling, antagonizing osteoblast differentiation and increasing osteoclast activity. From an analysis of the secretome of cultured differentiating myoblasts, we interestingly found the presence of Gal-3. After that, we confirmed that Gal-3 was expressed and released in the extracellular environment from myoblast cells during their differentiation into myotubes, as well as after mechanical strain. An in vivo analysis revealed that Gal-3 was triggered by trained exercise and was specifically produced by fast muscle fibers. Speculating a role for this peptide in the muscle-to-bone cross talk, a direct co-culture in vitro system, simultaneously combining media that were obtained from differentiated myoblasts and osteoblast cells, confirmed that Gal-3 is a mediator of osteoblast differentiation. Molecular and proteomic analyses revealed that the secreted Gal-3 modulated the biochemical processes occurring in the early phases of bone formation, in particular impairing the activity of the STAT3 and PDK1/Akt signaling pathways and, at the same time, triggering that one of Notch. Circulating Gal-3 also affected the expression of the most common factors involved in osteogenetic processes, including BMP-2, -6, and -7. Intriguingly, Gal-3 was able to interfere with the ability of differentiating osteoblasts to interact with the components of the extracellular bone matrix, a crucial condition required for a proper osteoblast differentiation. All in all, our evidence lays the foundation for further studies to present this lectin as a novel myokine involved in muscle-to-bone crosstalk.

Tunable Luminescent Properties and Multifunctional Imaging Applications of (Gd1-xRx)2O2S:Tb3+ (R = Y, La) Phosphor and Screen.

Gd2O2S:Tb3+ phosphor screens are widely used in image intensifiers, computed tomography, and neutron imaging. To improve the luminescent properties and thermal stability, (Gd1-xRx)2O2S:yTb3+ (R = Y, La) (x = 0, 0.05, 0.15, 0.25, and 0.35; y = 0.02, 0.04, 0.06, 0.08, and 0.10) phosphors were successfully prepared by the carbothermal reduction method. The luminescent spectra showed that the optimum concentrations of Tb3+ ions were 6 and 4 mol % when excited by 292 nm UV light and cathode ray, respectively. The emission wavelengths mainly peaked at 489 and 544 nm. It was found that the introduction of Y3+ ions could improve the luminescent intensity, and the luminescent intensity of (Gd1-xYx)2O2S:0.06Tb3+ was the highest at x = 0.25, while La3+ ions played the opposite role. Then, the thermal stability also improved, and the emission intensities of Gd2O2S:0.06Tb3+, (Gd0.75Y0.25)2O2S:0.06Tb3+, and (Gd0.75La0.25)2O2S:0.06Tb3+ phosphors at 423 K decreased to 66.22%, 68.23%, and 76.10% of the emission intensities at 303 K, respectively. Finally, the (Gd0.75Y0.25)2O2S:0.06Tb3+ phosphor screen was successfully prepared by the gravity deposition method and could be well imaged under UV light and cathode ray excitation with a CMOS camera. In summary, this study demonstrates that (Gd1-xRx)2O2S:Tb3+ (R = Y, La) is a phosphor with excellent luminescent and thermal stability properties and has great potential for application in the field of low-level-light night vision, nondestructive testing, and medical imaging.

Acetylation of TIR domains in the TLR4-Mal-MyD88 complex regulates immune responses in sepsis

Activation of the Toll-like receptor 4 (TLR4) by bacterial endotoxins in macrophages plays a crucial role in the pathogenesis of sepsis. However, the mechanism underlying TLR4 activation in macrophages is still not fully understood. Here, we reveal that upon lipopolysaccharide (LPS) stimulation, lysine acetyltransferase CBP is recruited to the TLR4 signalosome complex leading to increased acetylation of the TIR domains of the TLR4 signalosome. Acetylation of the TLR4 signalosome TIR domains significantly enhances signaling activation via NF-κB rather than IRF3 pathways. Induction of NF-κB signaling is responsible for gene expression changes leading to M1 macrophage polarization. In sepsis patients, significantly elevated TLR4-TIR acetylation is observed in CD16+ monocytes combined with elevated expression of M1 macrophage markers. Pharmacological inhibition of HDAC1, which deacetylates the TIR domains, or CBP play opposite roles in sepsis. Our findings highlight the important role of TLR4-TIR domain acetylation in the regulation of the immune responses in sepsis, and we propose this reversible acetylation of TLR4 signalosomes as a potential therapeutic target for M1 macrophages during the progression of sepsis.

OsNF-YB7 inactivates OsGLK1 to inhibit chlorophyll biosynthesis in rice embryo.

As a master regulator of seed development, Leafy Cotyledon 1 (LEC1) promotes chlorophyll (Chl) biosynthesis in Arabidopsis, but the mechanism underlying this remains poorly understood. Here, we found that loss of function of OsNF-YB7, a LEC1 homolog of rice, leads to chlorophyllous embryo, indicating that OsNF-YB7 plays an opposite role in Chl biosynthesis in rice compared with that in Arabidopsis. OsNF-YB7 regulates the expression of a group of genes responsible for Chl biosynthesis and photosynthesis by directly binding to their promoters. In addition, OsNF-YB7 interacts with Golden 2-Like 1 (OsGLK1) to inhibit the transactivation activity of OsGLK1, a key regulator of Chl biosynthesis. Moreover, OsNF-YB7 can directly repress OsGLK1 expression by recognizing its promoter in vivo, indicating the involvement of OsNF-YB7 in multiple regulatory layers of Chl biosynthesis in rice embryo. We propose that OsNF-YB7 functions as a transcriptional repressor to regulate Chl biosynthesis in rice embryo.

OsNF-YB7 inactivates OsGLK1 to inhibit chlorophyll biosynthesis in rice embryo

As a master regulator of seed development, Leafy Cotyledon 1 (LEC1) promotes chlorophyll (Chl) biosynthesis in Arabidopsis, but the mechanism underlying this remains poorly understood. Here, we found that loss of function of OsNF-YB7, a LEC1 homolog of rice, leads to chlorophyllous embryo, indicating that OsNF-YB7 plays an opposite role in Chl biosynthesis in rice compared with that in Arabidopsis. OsNF-YB7 regulates the expression of a group of genes responsible for Chl biosynthesis and photosynthesis by directly binding to their promoters. In addition, OsNF-YB7 interacts with Golden 2-Like 1 (OsGLK1) to inhibit the transactivation activity of OsGLK1, a key regulator of Chl biosynthesis. Moreover, OsNF-YB7 can directly repress OsGLK1 expression by recognizing its promoter in vivo, indicating the involvement of OsNF-YB7 in multiple regulatory layers of Chl biosynthesis in rice embryo. We propose that OsNF-YB7 functions as a transcriptional repressor to regulate Chl biosynthesis in rice embryo.

Activin A inhibits the migration of human lung adenocarcinoma A549 cells induced by EGF

Activin A, a member of the transforming growth factor β (TGF-β) superfamily, is involved in tumorigenesis and tumor progression. However, it remains unclear whether activin A can affect the migration of lung adenocarcinoma (LUAD) cells. In this study, the results of differentially expressed genes (DEGs) identification revealed that lung adenocarcinoma tissues exhibited lower expression of activin βA mRNA, but higher expression of epidermal growth factor (EGF) and MMP9 mRNA compared to nontumor tissues. Moreover, we found that activin A inhibited human LUAD A549 cell proliferation promoted by EGF. Additionally, EGF induced A549 cell migration in microfluidic device, while activin A attenuated EGF actions. Simultaneously, EGF increased the levels of migration-related proteins, but activin A played the opposite role. Furthermore, the study revealed that EGF upregulated the ratio of p-ERK/ERK in A549 cells, which was weakened by activin A, and A549 cell migration regulated by activin A was not related to calcium signaling. In addition, the inhibitory effect of activin A on EGF-induced A549 cell migration was attenuated by the ERK inhibitor FR180204. These findings demonstrate that activin A effectively hinders the migration of A549 cells induced by EGF through ERK1/2 signaling, suggesting that targeting activin A may hold promise in the treatment of EGF-dependent LUAD growth and metastasis.

OsWRKY70 Plays Opposite Roles in Blast Resistance and Cold Stress Tolerance in Rice

The transcription factor WRKYs play pivotal roles in the adapting to adverse environments in plants. Prior research has demonstrated the involvement of OsWRKY70 in resistance against herbivores and its response to abiotic stress. Here, we reported the functional analysis of OsWRKY70 in immunity against fungal diseases and cold tolerance. The results revealed that OsWRKY70 was induced by various Magnaporthe oryzae strains. Knock out mutants of OsWRKY70, which were generated by the CRISPR/Cas9 system, exhibited enhanced resistance to M. oryzae. This was consistent with fortifying the reactive oxygen species (ROS) burst after inoculation in the mutants, elevated transcript levels of defense-responsive genes (OsPR1b, OsPBZ1, OsPOX8.1 and OsPOX22.3) and the observation of the sluggish growth of invasive hyphae under fluorescence microscope. RNA sequencing (RNA-seq) and quantitative real-time PCR (qRT-PCR) validations demonstrated that differentially expressed genes were related to plant-pathogen interactions, hormone transduction and MAPK cascades. Notably, OsbHLH6, a key component of the JA signaling pathway, was down-regulated in the mutants compared to wild type plants. Further investigation confirmed that OsWRKY70 bound to the promoter of OsbHLH6 by semi-in vivo chromatin immunoprecipitation (ChIP). Additionally, the loss-function of OsWRKY70 impaired cold tolerance in rice. The enhanced susceptibility in the mutants characterized by excessive ROS production, elevated ion leakage rate and increased malondialdehyde content, as well as decreased activity of catalase (CAT) and peroxidase (POD) under low temperature stress was, which might be attributed to down-regulation of cold-responsive genes (OsLti6b and OsICE1). In conclusion, our findings indicate that OsWRKY70 negatively contributes to blast resistance but positively regulates cold tolerance in rice, providing a strategy for crop breeding with tolerance to stress.

Transcription factor Yin Yang 1 enhances epithelial-mesenchymal transition, migration, and stemness of non-small cell lung cancer cells by targeting sonic hedgehog.

Non-small cell lung cancer (NSCLC) is a frequent type of lung cancer. Transcription factor Yin Yang 1 (YY1), an endogenous transcription factor containing zinc finger structure, can accelerate NSCLC progression. However, the impact of YY1 on the stemness of NSCLC cells and the mechanism of promoting NSCLC cell progression is unclear. YY1 and Sonic hedgehog (Shh) expressions were monitored by RT-qPCR, western blot, and immunohistochemistry. Overall survival was tested through Kaplan-Meier analysis. The interaction between YY1 and Shh was confirmed. Then, cell migration, stemness, and epithelial-mesenchymal transition (EMT) were assessed with functional experiments in vitro and in vivo. YY1 and Shh were highly expressed in NSCLC tissues and positively correlated with the poor OS of NSCLC patients. Functional experiments denoted that YY1 or Shh overexpression could accelerate EMT, migration, and stemness of NSCLC cells, and YY1 or Shh knockdown played the opposite role to its overexpression. Mechanism analysis disclosed that Shh, as a target gene of YY1, was positively related to YY1. The rescued experiment manifested that Shh silencing could reverse the induction effect of YY1 overexpression on EMT, migration, and stemness of NSCLC cells. In vivo experiments also confirmed that YY1 could accelerate tumor growth and EMT and weaken apoptosis. YY1 promotes NSCLC EMT, migration, and stemness by Shh, which might be novel diagnostic markers and therapeutic targets for NSCLC therapy.

Selective hydrogenation of biphenyl to cyclohexylbenzene over Cu based catalysts

The Cu/Al2O3, Cu/MgAlO, Cu/MgO and Cu-Ni/MgAlO catalysts (60 wt%) were studied for the selective hydrogenation of biphenyl (BP) to cyclohexylbenzene (CHB). The results showed the relatively high dispersion but low reducibility of Cu in the Cu/Al2O3. The acidic surface of Al2O3 caused the electron-deficient Cu that enhanced the adsorption of aromatic rings and thus led to the higher intrinsic activity for the hydrogenation of aromatic rings over the Cu/Al2O3, while the basic surface of MgO played the just opposite roles. The Cu/MgAlO possessed the suitable surface acidity and basicity and thus the high density of surface Cu active sites. Thus, it exhibited the higher overall activity than the Cu/Al2O3 and Cu/MgO for the hydrogenation of BP. However, the heats for the adsorption of toluene and H2 were significantly lower on Cu than those on Ni, which accounted for that the Ni was much more active than Cu for the hydrogenation of BP and CHB. Further studies showed that the activation energies for the hydrogenation of BP and CHB on Cu were high and differ greatly, resulting in the high conversion of BP with high selectivity to CHB over the Cu catalysts. On the other hand, the activation energies were significantly lower and did not differ so much on Ni, leading to the high conversion of BP and CHB for the formation of bicyclohexyl. Finally, the addition of a small amount of Ni (1 wt%) into the Cu/MgAlO greatly increased the conversion of BP under relative lower temperature while maintained the high selectivity to CHB.

The different effects of four adenosine receptors in liver fibrosis.

The adenosine-adenosine receptor pathway plays important roles in the immune system and inflammation. Four adenosine receptors (i.e., A1R, A2AR, A2BR, and A3R) have been identified. However, the roles of these receptors were different in the disease progress and even play opposite roles in the same disease. This study aims to investigate the roles of A1R/A2AR/A2BR/A3R activation in liver fibrosis. Intraperitoneal injection of CCl4 into C57BL/6 mice was used to induce liver fibrosis in the models. Adenosine receptor agonists CCPA, CGS21680, BAY 60-6583, and namodenoson were used for A1R/A2AR/A2BR/A3R activation, respectively. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were used to evaluate the liver function. Hematoxylin and eosin (H&E) staining was used to investigate the pathological damage. Masson staining and Sirius Red staining were performed to evaluate the degree of collagen deposition. CCK8 and scratch assays were used to investigate the proliferation and migration ability of hepatic stellate cells (HSCs). By using liver fibrosis mouse models, we observed that the A1R and A2AR agonists aggravated liver fibrosis, characterized by increasing ALT and AST levels, more serious liver pathological damage, and collagen deposition. However, the A2BR and A3R agonists alleviated liver fibrosis. Moreover, the A1R and A2AR agonist treatment promotes the proliferation and migration of HSC line LX2, while A2BR and A3R agonist treatment inhibited LX2 proliferation and migration. Consistently, A1R and A2AR agonist treatment elevated the expression of α-SMA and Col1α1 in LX2, whereas A2BR and A3R agonist treatment inhibited the expression of α-SMA and Col1α1 in LX2 cells. Additionally, 5'-N-ethyl-carboxamidoadenosine (NECA), a metabolically stable adenosine analog, alleviated liver fibrosis and inhibited LX2 cell activity, proliferation, and migration. This study demonstrated the different roles of A1R/A2AR/A2BR/A3R during liver fibrosis development via regulating the HSC activity and proliferation.

TIPE2 inhibits the migration and invasion of epithelial ovarian cancer cells by targeting Smad2 to reverse TGF-β1-induced EMT.

Epithelial ovarian cancer is the deadliest gynecologic malignancy, characterized by high metastasis. Transforming growth factor-β1 (TGF-β1) drives epithelial- mesenchymal transformation (EMT), a key process in tumor metastasis. Tumor necrosis factor-α-induced protein 8 (TNFAIP8)-like 2 (TIPE2) acts as a negative regulator of innate and adaptive immunity and involves in various cancers. However, its relationship with TGF-β1 in ovarian cancer and its role in reversing TGF-β1-induced EMT remain unclear. This study examined TIPE2 mRNA and protein expression using quantitative RT-PCR (qRT-PCR), western blot and immunohistochemistry. The effects of TIPE2 overexpression and knockdown on the proliferation, migration and invasion of epithelial ovarian cancer cells were assessed through 5-ethynyl-2-deoxyuridine, colony-forming, transwell migration and invasion assays. The relationship between TIPE2 and TGF-β1 was investigated using qRT-PCR and enzyme-linked immunosorbent assay, while the interaction between TIPE2 and Smad2 was identified via co-immunoprecipitation. The results revealed that TIPE2 protein was significantly down-regulated in epithelial ovarian cancer tissues and correlated with the pathological type of tumor, patients' age, tumor differentiation degree and FIGO stage. TIPE2 and TGF-β1 appeared to play an opposite role to each other during the progression of human ovarian cancer cells. Furthermore, TIPE2 inhibited the metastasis and EMT of ovarian cancer cells by combining with Smad2 invitro or in an intraperitoneal metastasis model. Consequently, these findings suggest that TIPE2 plays a crucial inhibitory role in ovarian cancer metastasis by modulating the TGF-β1/Smad2/EMT signaling pathway and may serve as a potential target for ovarian cancer, providing important direction for future diagnostic and therapeutic strategies.