Myeloid neddylation targets IRF7 and promotes host innate immunity against RNA viruses.

Neddylation, an important type of post-translational modification, has been implicated in innate and adapted immunity. But the role of neddylation in innate immune response against RNA viruses remains elusive. Here we report that neddylation promotes RNA virus-induced type I IFN production, especially IFN-α. More importantly, myeloid deficiency of UBA3 or NEDD8 renders mice less resistant to RNA virus infection. Neddylation is essential for RNA virus-triggered activation of Ifna gene promoters. Further exploration has revealed that mammalian IRF7undergoes neddylation, which is enhanced after RNA virus infection. Even though neddylation blockade does not hinder RNA virus-triggered IRF7 expression, IRF7 mutant defective in neddylation exhibits reduced ability to activate Ifna gene promoters. Neddylation blockade impedes RNA virus-induced IRF7 nuclear translocation without hindering its phosphorylation and dimerization with IRF3. By contrast, IRF7 mutant defective in neddylation shows enhanced dimerization with IRF5, an Ifna repressor when interacting with IRF7. In conclusion, our data demonstrate that myeloid neddylation contributes to host anti-viral innate immunity through targeting IRF7 and promoting its transcriptional activity.

New Fields, New Opportunities and New Challenges: Circularly Polarized Multiple Resonance Thermally Activated Delayed Fluorescence Materials.

Circularly polarized luminescence (CPL) materials that concurrently exhibit high efficiency and narrowband emission are extremely promising applications in 3D and wide color gamut display. By merging the CPL optical property and multiple resonance (MR) induced thermally activated delayed fluorescence (TADF) characteristic into one molecule, a new strategy, namely CP-MR-TADF, is proposed to generate organic emitters with CPL activity, TADF and narrowband emission. High-performance red, green and blue CP-MR-TADF emitters have been developed following this strategy. Herein, the present status and progress of CP-MR-TADF materials in the field of organic light-emitting diodes (OLEDs) is summarized. Finally, for this rapidly growing new research field, the future opportunities are forecasted and the present challenges are discussed.

Associations among retrospective parenting styles, retrospective food parenting, and current eating behaviors in Chinese adults.

The current study explored the relationships between retrospective parenting styles and food parenting in childhood (≤ 12 years old) and Chinese adults' current maladaptive and adaptive eating behaviors. We recruited 501 Chinese adults (50.30% men, aged 19-46 years). A set of questionnaires were used to measure retrospective parenting styles (i.e., emotional warmth, rejection, and overprotection), food parenting (i.e., parental concern, monitoring, pressure to eat, and restriction), and current maladaptive (i.e., disordered eating) and adaptive (i.e., intuitive eating) eating behaviors. Correlation and mediation analyses were employed to analyze these data. Results revealed that retrospective parenting styles and food parenting were significantly related to current maladaptive and adaptive eating behaviors in both Chinese men and women. Mediation analyses showed that higher retrospective parental warmth was related to higher retrospective parental concern which, in turn, was related to higher current disordered eating in men (indirect effect = 0.14, 95% CI 0.08, 0.24). Furthermore, higher retrospective parental overprotection was related to higher retrospective parental pressure to eat which, in turn, was related to higher current disordered eating in men (indirect effect = 0.06, 95% CI 0.01, 0.14). For women, higher retrospective parental warmth was associated with higher retrospective parental concern which, in turn, was associated with lower current intuitive eating in women (indirect effect = -0.04, 95% CI = -0.10, -0.01). Furthermore, higher retrospective parental overprotection was associated with higher retrospective parental concern which, in turn, was associated with lower current intuitive eating in women (indirect effect = -0.03, 95% CI = -0.08, -0.004). The findings indicate the importance of including childhood parenting styles and food parenting in future research and intervention of adults' current maladaptive and adaptive eating behaviors.

The six-year biochar retention interacted with fertilizer addition alters the soil organic nitrogen supply capacity in bulk and rhizosphere soil.

Nitrogen fractions in soil, like organic nitrogen, mineral nitrogen, and free amino acids, are sensitive pointers to the soil nitrogen pools involved in nutrient cycling. As a potential improvement measure, biochar might improve soil fertility and nutrient availability. However, few studies have focused on the long-term effects of biochar retention on the soil nitrogen supply capacity of bulk and rhizosphere soil in brown earth. Therefore, a six-year field experiment was conducted in 2013, concentrating on the impact of biochar retention on soil nitrogen fractions. Four biochar rates were tested: no biochar amendment (CK); 15.75 t ha-1 of biochar (BC1); 31.5 t ha-1 of biochar (BC2); 47.25 t ha-1 of biochar (BC3). Our results showed that the elevated application rates significantly enhanced soil organic matter (SOM), and total nitrogen (TN), and improved pH in both bulk and rhizosphere soils. Acid-hydrolyzable nitrogen (AHN) content in biochar treatments was higher than that of CK in bulk and rhizosphere soil. The content of non-hydrolyzable nitrogen (NHN) was increased in 47.25 t ha-1 of biochar retention. Ammonium nitrogen (AN) and amino sugar nitrogen (ASN) contents were higher in bulk soil than in rhizosphere soil. Neutral amino acid contents were the highest both in bulk and rhizosphere soil. Principal component analysis (PCA) showed that soil organic nitrogen was significantly influenced by BC3 treatment in bulk soil, and largely influenced by other treatments in rhizosphere soil. Partial least square path modeling (PLSPM) revealed that NH4+-N was mainly derived from amino acid nitrogen (AAN) and AN in bulk soil and AAN and ASN in rhizosphere soil. These results indicate that different biochar retention rates contributed to improve soil nutrients. Amino acid nitrogen was the prominent nitrogen source of NH4+-N in bulk and rhizosphere soils.

Frontier Molecular Orbital Engineering: Constructing Highly Efficient Narrowband Organic Electroluminescent Materials.

It is of great strategic significance to develop highly efficient narrowband organic electroluminescent materials that can be utilized to manufacture ultra-high-definition (UHD) displays and meet or approach the requirements of Broadcast Television 2020 (B.T.2020) color gamut standards. This motif poses challenges for molecular design and synthesis, especially for developing generality, diversity, scalability, and robustness of molecular structures. The emergence of multiple resonance thermally activated delayed fluorescence (MR-TADF) emitters has ingeniously solved the problems and demonstrated bright application prospects in the field of UHD displays, sparking a research boom. This Minireview summarizes the research endeavors of narrowband organic electroluminescent materials, with emphasis on the tremendous contribution of frontier molecular orbital engineering (FMOE) strategy. It combines the outstanding advantages of MR framework and donor-acceptor (D-A) structure, and can achieve red-shift and narrowband emission simultaneously, which is of great significance in the development of long-wavelength narrowband emitters with emission maxima especially exceeding 500 nm. We hope that this Minireview would provide some inspiration for what could transpire in the future.

Precise Regulation of Emission Maxima and Construction of Highly Efficient Electroluminescent Materials with High Color Purity.

Advanced multiple resonance induced thermally activated delayed fluorescence (MR-TADF) emitters have emerged as a privileged motif for applications in organic light-emitting diodes (OLEDs), because they furnish highly tunable TADF characteristics and high color purity emission. Herein, based on the unique nitrogen-atom embedding molecular engineering (NEME) strategy, a series of compounds BN-TP-Nx (x=1, 2, 3, 4) have been customized. The nitrogen-atom anchored at different position of triphenylene hexagonal lattice entails varying degrees of perturbation to the electronic structure. The newly-constructed emitters have demonstrated the precise regulation of emission maxima of MR-TADF emitters to meet the actual industrial demand, and further enormously enriched the MR-TADF molecular reservoir. The BN-TP-N3-based OLED exhibits ultrapure green emission, with peak of 524 nm, full-width at half-maximum (FWHM) of 33 nm, Commission Internationale de L'Eclairage (CIE) coordinates of (0.23, 0.71), and maximum external quantum efficiency (EQE) of 37.3 %.

Relationships between retrospective parental feeding practices and Chinese university students' current appetitive traits, weight status, and satisfaction with food-related life.

Accumulating evidence suggests that parental feeding practices during childhood are related to adults' eating behaviors and weight status, but research exploring these relationships is largely conducted in Western contexts. However, China, a country that holds the largest world population, has distinct patterns of eating habits and food culture from Western countries. Therefore, the present study aimed to examine relationships between retrospective parental feeding practices (e.g., concern, monitoring, pressure to eat, and restriction) and current body mass index (BMI) and satisfaction with food-related life in a sample of 476 Chinese university students (195 men; Mage = 19.78 years, SD = 1.23). We also examined whether appetitive traits mediated these associations. Retrospective parental feeding practices were significantly related with participants' current BMI (concern: r = 0.26, p < .001; pressure to eat: r = -0.15, p < .001) and satisfaction with food-related life (concern: r = 0.15, p < .001; monitoring: r = 0.12, p = .009; pressure to eat: r = 0.13, p = .006; restriction: r = 0.16, p < .001). Relationships were partially mediated by young adults' current appetitive traits (e.g., enjoyment of food, emotional overeating, satiety responsiveness, slowness in eating). These findings suggest that retrospective parental feeding practices are important correlates of young adults' current weight status and satisfaction with food-related life, and that appetitive traits partially explain these relationships in the Chinese context.

Constructing Organic Electroluminescent Material with Very High Color Purity and Efficiency Based on Polycyclization of the Multiple Resonance Parent Core.

Multiple resonance thermally activated delayed fluorescence (MR-TADF) compounds have set off an upsurge of research because of their tremendous application prospects in the field of wide color gamut display. Herein, we propose a novel MR-TADF molecular construction paradigm based on polycyclization of the multiple resonance parent core, and construct a representative multiple resonance polycyclic aromatic hydrocarbon (MR-PAH) based on the para-alignment of boron and nitrogen atoms into a six-membered ring (p-BNR). Through the retrosynthesis analysis, a concise synthesis strategy with wide applicability has been proposed, encompassing programmed sequential boron esterification, Suzuki coupling and Scholl oxidative coupling. The target model molecule BN-TP shows green fluorescence with an emission peak at 523 nm and a narrow full-width at half-maximum (FWHM) of 34 nm. The organic light-emitting diode (OLED) employing BN-TP as an emitter exhibits ultrapure green emission with Commission Internationale de L'Eclairage (CIE) coordinates of (0.26, 0.70), and achieves a maximum external quantum efficiency (EQE) of 35.1 %.

Transcriptome and metabolome analysis of stress tolerance to aluminium in Vitis quinquangularis.

MAIN CONCLUSION: Transcriptional and metabolic regulation of aluminium tolerance of Chinese wild Vitis quinquangularis after Al treatment for 12 h: genes and pathways related to stress resistance are activated to cope with Al stress. The phytotoxicity of aluminium (Al) has become a major issue in inhibiting plant growth in acidic soils. Chinese wild Vitis species have excellent stress resistance. In this study, to explore the mechanism underlying Al tolerance in Chinese wild Vitis quinquangularis, we conducted a transcriptome analysis to understand the changes in gene expression and pathways in V. quinquangularis leaves after Al treatment for 12 h (Al_12 h). Compared with the control (CK) treatment, 2266 upregulated differentially expressed genes (DEGs) and 2943 downregulated DEGs were identified after Al treatment. We analysed the top 60 upregulated DEGs and found that these genes were related mostly to cell wall organization or biogenesis, transition metal ion binding, etc. Another analysis of all the upregulated DEGs showed that genes related to the ABC transport pathway, salicylic acid (SA), jasmonic acid (JA) and abscisic acid (ABA) hormone signalling pathway were expressed. Transcriptome and metabolome analysis revealed that genes and metabolites (phenylalanine, cinnamate and quercetin) related to the phenylalanine metabolic pathway were expressed. In summary, the results provide a new contribution to a better understanding of the metabolic changes that occur in grapes after Al stress as well as to research on improving the resistance of grape cultivars.

A novel Danshensu/tetramethylpyrazine protects against Myocardial Ischemia Reperfusion Injury in rats.

A new Danshensu/tetramethylpyrazine derivative (ADTM) with cardio-protection effects such as antioxidant, arterial relaxation, pro-angiogenesis and antiplatelet activities. Platelet activating factor receptor (PAFR) plays a key role in myocardial ischemia reperfusion (MIR) injury. This study aims to investigate the protective role of ADTM in MIR injury and clarify the potential role of PAFR. We measured the effects of ADTM on MIR injury in rats in vivo and hypoxia re-oxygenation (HR) injury in neonatal rat ventricular myocytes (NRVMs) in vitro. The results show that ADTM can significantly improve the IR-induced decline in heart function as increasing EF and FS, and restore the decreased cardiac hemodynamic parameters (LVSP, ± dp/dt max) and increased the level of LVEDP, decrease the infarct size of damaged myocardium and lactate dehydrogenase (LDH) activity in serum. Additionally, ADTM inhibits cardiomyocytes apoptosis, caspase-3 activity, and inflammatory response as well as down-regulates the MIR-induced IL-1ß and TNFα production. Next, PAFR expression was significantly down-regulated in cardiomyocytes of MIR model in vivo and in vitro after treated with ADTM compare to IR group. At the same time, ADTM and PAFR small interfering RNA (siRNA) could inhibit cardiomyocytes apoptosis and inflammation during HR, while PAF presents the opposite effect. Furthermore, the above effects of PAF in HR induced cardiomyocytes were reversed by co-treatment of ADTM. Our findings demonstrate for the first time that ADTM protects against MIR injury through inhibition of PAFR signaling, which provides a new treatment for MIR.

Access to and Reactivity of Fe0 , Fe-I , FeI , and FeII PCcarbene P Pincer Complexes.

Despite their promising metal-ligand cooperative reactivity, PCcarbene P pincer ligands are rarely reported for first-row transition-metal centres. Using a dehydration methodology, we report access to an Fe0 PCcarbene P pincer complex (1) that proceeds via an isolated α-hydroxylalkyl hydrido complex (3). Reversible carbonyl migration to the carbene position in 1 is found to allow coordination chemistry and E-H bond addition (E=H, B, Cl) across the iron-carbene linkage, representing a unique mechanism for metal-ligand cooperativity. The PCcarbene P pincer ligand is also found to stabilize formal FeII , FeI , and Fe-I oxidation states, as demonstrated with synthesis and characterization of the complexes [11-X][BArF 20 ] (X=Br, I), 12, and K[13]. Compound K[13] is found to be highly reactive, and abstracts hydrogen from a range of aliphatic C-H sources. Computational analysis by DFT suggests that the formal FeI and Fe-I complexes contain significant carbene radical character. The ability of the PCcarbene P ligand scaffold to partake in metal-ligand cooperativity and to support a range of iron oxidation states renders it as potentially useful in many catalytic applications.

The Effect of Transcription Factor MYB14 on Defense Mechanisms in Vitis quinquangularis-Pingyi.

In the current study, we identified a transcription factor, MYB14, from Chinese wild grape, Vitis quinquangularis-Pingyi (V. quinquangularis-PY), which could enhance the main stilbene contents and expression of stilbene biosynthesis genes (StSy/RS) by overexpression of VqMYB14. The promoter of VqMYB14 (pVqMYB14) was shown to be induced as part of both basal immunity (also called pathogen-associated molecular pattern (PAMP)-triggered immunity, PTI) and effector-triggered immunity (ETI), triggered by the elicitors flg22 and harpin, respectively. This was demonstrated by expression of pVqMYB14 in Nicotiana benthamiana and Vitis. We identified sequence differences, notably an 11 bp segment in pVqMYB14 that is important for the PTI/ETI, and particularly for the harpin-induced ETI response. In addition, we showed that activation of the MYB14 promoter correlates with differences in the expression of MYB14 and stilbene pattern induced by flg22 and harpin. An experimental model of upstream signaling in V. quinquangularis-PY is presented, where early defense responses triggered by flg22 and harpin partially overlap, but where the timing and levels differ. This translates into a qualitative difference with respect to patterns of stilbene accumulation.

Exergy Analysis of Two-Stage Organic Rankine Cycle Power Generation System.

Organic Rankine cycle (ORC) power generation is an effective way to convert medium and low temperature heat into high-grade electricity. In this paper, the subcritical saturated organic Rankine cycle system with a heat source temperature of 100~150 °C is studied with four different organic working fluids. The variations of the exergy efficiencies for the single-stage/two-stage systems, heaters, and condensers with the heat source temperature are analyzed. Based on the condition when the exergy efficiency is maximized for the two-stage system, the effects of the mass split ratio of the geothermal fluid flowing into the preheaters and the exergy efficiency of the heater are studied. The main conclusions include: The exergy efficiency of the two-stage system is affected by the evaporation temperatures of the organic working fluid in both the high temperature and low temperature cycles and has a maximum value. Under the same heat sink and heat source parameters, the exergy efficiency of the two-stage system is larger than that of the single-stage system. For example, when the heat source temperature is 130 °C, the exergy efficiency of the two-stage system is increased by 9.4% compared with the single-stage system. For the two-stage system, analysis of the four organic working fluids shows that R600a has the highest exergy efficiency, although R600a is only suitable for heat source temperature below 140 °C, while other working fluids can be used in systems with higher heat source temperatures. The mass split ratio of the fluid in the preheaters of the two-stage system depends on the working fluid and the heat source temperature. As the heat source temperature increases, the range of the split ratio becomes narrower, and the curves are in the shape of an isosceles triangle. Therefore, different working fluids are suitable for different heat source temperatures, and appropriate working fluid and split ratio should be determined based on the heat source parameters.

Constructing Charge-Transfer Excited States Based on Frontier Molecular Orbital Engineering: Narrowband Green Electroluminescence with High Color Purity and Efficiency.

The design and synthesis of organic materials with a narrow emission band in the longer wavelength region beyond 510 nm remain a great challenge. For constructing narrowband green emitters, we propose a unique molecular design strategy based on frontier molecular orbital engineering (FMOE), which can integrate the advantages of a twisted donor-acceptor (D-A) structure and a multiple resonance (MR) delayed fluorescence skeleton. Attaching an auxiliary donor to a MR skeleton leads to a novel molecule with twisted D-A and MR structure characteristics. Importantly, a remarkable red-shift of the emission maximum and a narrowband spectrum are achieved simultaneously. The target molecule has been employed as an emitter to fabricate green organic light-emitting diodes (OLEDs) with Commission Internationale de L'Eclairage (CIE) coordinates of (0.23, 0.69) and a maximum external quantum efficiency (EQE) of 27.0 %.

The transcription factor MYB15 is essential for basal immunity (PTI) in Chinese wild grape.

MAIN CONCLUSION: MYB15 promoter of Vitis quinquangularis has potential as a target for disease resistance breeding, and its involvement in PTI is associated with a range of defense mechanisms. China is a center of origin for Vitis and is home to diverse wild Vitis genotypes, some of which show superior pathogen resistance, although the underlying molecular basis for this has not yet been elucidated. In the current study, we identified a transcription factor, MYB15, from the Chinese wild grape, Vitis quinquangularis, whose promoter region (pVqMYB15) was shown to be induced by basal immunity (also called PAMP-triggered immunity, PTI) triggered by flg22, following heterologous expression in Nicotiana benthamiana and homologous expression in grapevine. By analyzing the promoter structure and activity, we identified a unique 283 bp sequence that plays a key role in the activation of basal immunity. In addition, we showed that activation of the MYB15 promoter correlates with differences in the expression of MYB15 and RESVERATROL SYNTHASE (RS) induced by the flg22 elicitor. We further tested whether the MYB15 induction triggered by flg22 was consistent with MYB15 and RS expression following inoculation with Plasmopara viticola in grape (V. quinquangularis and Vitis vinifera) leaves. Mapping upstream signals, we found that calcium influx, an RboH-dependent oxidative burst, an MAPK cascade, and jasmonate and salicylic acid co-contributed to flg22-triggered pVqMYB15 activation. Our data suggest that the MYB15 promoter has potential as a target for disease resistance breeding, and its involvement in PTI is associated with a range of defense mechanisms.

Leucine-rich repeat and sterile alpha motif containing 1 promotes the oncogenic growth of human hepatocellular carcinoma cells.

BACKGROUND: Hepatocellular carcinoma (HCC), the most common primary cancer of the liver, is one of the most common malignancies and the leading cause of cancer-related death worldwide. Leucine-rich repeat and sterile alpha motif containing 1 (LRSAM1) is an E3 ubiquitin ligase involved in diverse cellular activities, including the regulation of cargo sorting, cell adhesion and antibacterial autophagy. The role of LRSAM1 in HCC remains unknown. METHODS: In this study, we reviewed the TCGA database and then performed gain-of-function and loss-of-function analyses of LRSAM1 in HCC cell lines. RESULTS: We found that the mRNA expression level of LRSAM1 was significantly increased in clinical HCC tissues in the TCGA database. Transient LRSAM1 knockdown in several human HCC cell lines led to reduced growth in conventional culture conditions. Stable LRSAM1 knockdown in HepG2 cells led to impaired anchorage-independent growth whereas its stable ectopic overexpression yielded the opposite effects. LRSAM1 overexpression in HepG2 cells enhanced in vivo tumorigenicity, whereas LRSAM1 knockdown in this cell line significantly impaired tumor growth. CONCLUSIONS: Our data suggest that LRSAM1 promotes the oncogenic growth of human HCC cells, although the underlying mechanisms remain to be explored.

RACK1 deficiency synergizes with all-trans retinoic acid to induce apoptosis in human acute promyelocytic leukemia cells.

As a classic differentiation agent, all-trans retinoic acid (ATRA) has been widely used in the treatment of acute promyelocytic leukemia (APL). However, the clinical application of ATRA has strict limitations, for its severe side effects due to the accumulation of peripheral blood leukocytes. The scaffold protein RACK1 (Receptor for activated C kinase 1), which regulates multiple signaling pathways, has been proposed to contribute to the survival of leukemic progenitors. But it remains unclear whether it is also involved in the oncogenic growth of APL. In the present study, we demonstrate that silencing of endogenous RACK1 expression synergized with ATRA to promote the death of NB4 and HL-60 APL cells without effect on cell differentiation induced by ATRA. Interestingly, RACK1 knockdown combined with ATRA treatment mainly induces apoptosis. It is distinct to the necrotic cell death induced by idarubicin in combination with ATRA, a regimen extensively used in the clinic to prevent neutrophil accumulation. Further exploration revealed that the lysosome-autophagy pathway is likely to be responsible for the anti-apoptotic role of RACK1. Taken together, our findings indicate that RACK1 is essential in maintaining the malignant features of APL, and targeting RACK1 may have promising therapeutic implications in the treatment of APL.

Ultrahigh Flux Thin Film Boiling Heat Transfer Through Nanoporous Membranes.

Phase change heat transfer is fundamentally important for thermal energy conversion and management, such as in electronics with power density over 1 kW/cm2. The critical heat flux (CHF) of phase change heat transfer, either evaporation or boiling, is limited by vapor flux from the liquid-vapor interface, known as the upper limit of heat flux. This limit could in theory be greater than 1 kW/cm2 on a planar surface, but its experimental realization has remained elusive. Here, we utilized nanoporous membranes to realize a new "thin film boiling" regime that resulted in an unprecedentedly high CHF of over 1.2 kW/cm2 on a planar surface, which is within a factor of 4 of the theoretical limit, and can be increased to a higher value if mechanical strength of the membranes can be improved (demonstrated with 1.85 kW/cm2 CHF in this work). The liquid supply is achieved through a simple nanoporous membrane that supports the liquid film where its thickness automatically decreases as heat flux increases. The thin film configuration reduces the conductive thermal resistance, leads to high frequency bubble departure, and provides separate liquid-vapor pathways, therefore significantly enhances the heat transfer. Our work provides a new nanostructuring approach to achieve ultrahigh heat flux in phase change heat transfer and will benefit both theoretical understanding and application in thermal management of high power devices of boiling heat transfer.

Receptor for activated C kinase 1 promotes hepatocellular carcinoma growth by enhancing mitogen-activated protein kinase kinase 7 activity.

UNLABELLED: c-Jun N-terminal protein kinase (JNK) is a member of the mitogen-activated protein kinase (MAPK) superfamily. The activation of JNK is mediated by sequential protein phosphorylation through a MAPK module, namely, MAPK kinase kinase (MAP3K or MEKK) → MAPK kinase (MAP2K or MKK) → MAPK. Elevated levels of JNK activity have been frequently observed in hepatocellular carcinoma (HCC) and have been demonstrated to contribute to HCC growth by promoting HCC cell proliferation and resistance to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)- or Fas-mediated apoptosis. Chronic inflammation contributes to the up-regulation of JNK activity in HCC. However, it remains unknown whether aberrant JNK activity also results from some cell intrinsic defect(s). Here, we show that receptor for activated C kinase 1 (RACK1), an adaptor protein implicated in the regulation of multiple signaling pathways, could engage in a direct interaction with MKK7, the JNK-specific MAP2K, in human HCC cells. Levels of RACK1 protein show correlation with the activity of the JNK pathway in human HCC tissues and cell lines. RACK1 loss-of-function or gain-of-function analyses indicate that RACK1 enhances MKK7/JNK activity in human HCC cells. Further exploration reveals that the interaction of RACK1 with MKK7 is required for the enhancement of MKK7/JNK activity by RACK1. RACK1/MKK7 interaction facilitates the association of MKK7 with MAP3Ks, thereby enhancing MKK7 activity and promoting in vitro HCC cell proliferation and resistance to TRAIL- or Fas-mediated apoptosis as well as in vivo tumor growth. CONCLUSION: Overexpressed RACK1 augments JNK activity and thereby promotes HCC growth through directly binding to MKK7 and enhancing MKK7 activity.

Disruption of TAB1/p38α interaction using a cell-permeable peptide limits myocardial ischemia/reperfusion injury.

Targeting the adaptor protein (transforming growth factor-ß (TGF-ß)-activated protein kinase 1 (TAK1)-binding protein 1) (TAB1)-mediated non-canonical activation of p38α to limit ischemia/reperfusion (I/R) injury after an acute myocardial infarction seems to be attractive since TAB1/p38α interaction occurs specifically in very limited circumstances and possesses unique structural basis. However, so far no TAB1/p38α interaction inhibitor has been reported due to the limited knowledge about the interfaces. In this study, we sought to identify key amino acids essential for the unique mode of interaction with computer-guided molecular simulations and molecular docking. After validation of the predicted three-dimensional (3-D) structure of TAB1/p38α complex, we designed several peptides and evaluated whether they could block TAB1/p38α interaction with selectivity. We found that a cell-permeable peptide worked as a selective TAB1/p38α interaction inhibitor and decreased myocardial I/R injury. To our knowledge, this is the first TAB1/p38α interaction inhibitor.