Intestinal Tissue, Digestive Enzyme, and Antioxidant Enzyme Activities in the Early Development Stage of Endangered Brachymystax tsinlingensis.

This work explores the digestive system characteristics of Brachymystax tsinlingensis during early developmental stages and aims to solve the problem of high lethality of fry during the transgression period, which is crucial for the artificial propagation and population conservation of endangered fishes. This study was carried out on intestinal tissue, digestive enzymes, and antioxidant enzyme activities in the early development stage of Brachymystax tsinlingensis. Ten random samples during endogenous nutrition (7, 10, and 11 days after hatching), mixed nutrition (13 and 19 DAH), and exogenous nutrition (31, 33, 39, 45, and 73 DAH) were collected by histological and biochemical analysis methods. The results showed that the intestine of Brachymystax tsinlingensis already has four layers initially at 7 DAH, and the intestinal gland tissue is evident at 73 DAH. The contents of total protein (TP) and the activities of lipase (LPS) and trypsin (TPS) were maximal at 39 DAH, and the activities were 3.20 ± 0.26 mg/mL, 2.52 ± 0.69 U/g, and 2717.45 ± 295.26 U/mg, respectively. Catalase (CAT) and glutathione peroxidase (GSH-PX) activities both showed the lowest values at 39 DAH, which were 0.57 ± 0.11 U/mg and 3.35 ± 0.94 U/mg, respectively. The activity of amylase (AMS) and the content of malonaldehyde (MDA) increased, and the highest values were reached at 45 DAH (1.32 ± 0.41 U/mg) and 73 DAH (1.29 ± 0.43 nmoL/mg), respectively. Superoxide dismutase (SOD) and GSH-PX activities both showed a peak value at 7 DAH (126.58 ± 20.13 U/mg and 6.47 ± 1.86 U/mg). Overall, the changes in intestinal tissue, digestive enzymes, and antioxidant enzyme activities at 39 DAH of Brachymystax tsinlingensis are inseparable from different vegetative stages during the developmental period, and these results can provide a reference for the proliferation and cultivation of Brachymystax tsinlingensis resources.

Interfering Josephson diode effect in Ta2Pd3Te5 asymmetric edge interferometer.

Edge states in topological systems have attracted great interest due to their robustness and linear dispersions. Here a superconducting-proximitized edge interferometer is engineered on a topological insulator Ta2Pd3Te5 with asymmetric edges to realize the interfering Josephson diode effect (JDE), which hosts many advantages, such as the high efficiency as much as 73% at tiny applied magnetic fields with an ultra-low switching power around picowatt. As an important element to induce such JDE, the second-order harmonic in the current-phase relation is also experimentally confirmed by half-integer Shapiro steps. The interfering JDE is also accompanied by the antisymmetric second harmonic transport, which indicates the corresponding asymmetry in the interferometer, as well as the polarity of JDE. This edge interferometer offers an effective method to enhance the performance of JDE, and boosts great potential applications for future superconducting quantum devices.

Comparative study on CeO2 catalysts with different morphologies and exposed facets for catalytic ozonation: performance, key factor and mechanism insight.

Morphology and facet effects of metal oxides in heterogeneous catalytic ozonation (HCO) are attracting increasing interests. In this paper, the different HCO performances for degradation and mineralization of phenol of seven ceria (CeO2) catalysts, including four with different morphologies (nanorod, nanocube, nanooctahedron and nanopolyhedron) and three with the same nanorod morphology but different exposed facets, are comparatively studied. CeO2 nanorods with (110) and (100) facets exposed show the best performance, much better than that of single ozonation, while CeO2 nanocubes and nanooctahedra show performances close to single ozonation. The underlying reason for their different HCO performances is revealed using various experimental and density functional theory (DFT) calculation results and the possible catalytic reaction mechanism is proposed. The oxygen vacancy (OV) is found to be pivotal for the HCO performance of the different CeO2 catalysts regardless of their morphology or exposed facet. A linear correlation is discerned between the rate of catalytic decomposition of dissolved ozone (O3) and the density of Frenkel-type OV. DFT calculations and in-situ spectroscopic studies ascertain that the existence of OV can boost O3 activation on both the hydroxyl (OH) and Ce sites of CeO2. Conversely, various facets without OV exhibit similar O3 adsorption energies. The OH group plays an important role in activating O3 to produce hydroxyl radical (∙OH) for improved mineralization. This work may offer valuable insights for designing Facet- and OV-regulated catalysts in HCO for the abatement of refractory organic pollutants.

Nucleobase-Coupled Xanthones with Anti-ROS Effects from Marine-Derived Fungus Aspergillus sydowii.

A MS/MS-based molecular networking approach compared to the Global Natural Product Social Molecular Networking library, in association with genomic annotation of natural product biosynthetic gene clusters within a marine-derived fungus, Aspergillus sydowii, identified a suite of xanthone metabolites. Chromatographic techniques applied to the cultured fungus led to the isolation of 11 xanthone-based alkaloids, dubbed sydoxanthones F-M. The structures of these alkaloids were elucidated using extensive spectroscopic data, including electronic circular dichroism and single-crystal X-ray diffraction data for configurational assignments. Among these analogues, sydoxanthones F-K exhibit structure features typical of nucleobase-coupled xanthones, with sydoxanthone H being an N-bonded xanthone dimer. Notably, (±)sydoxanthones F (1a/1b), (±)sydoxanthones H (3b/3a), and (±)sydoxanthones J (5b/5a) are enantiomeric pairs, while sydoxanthones G (2), I (4), and K (6) are stereoisomers of 1, 3, and 5, respectively. Furthermore, (+)sydoxanthone H (3a) demonstrated significant rescue of cell viability in H2O2-injuried SH-SY5Y cells by inhibiting reactive oxygen species production, suggesting its potential for neuroprotection.

Parental Burnout, Negative Parenting Style, and Adolescents' Development.

Research on parental burnout has focused more on its antecedents than on its consequences. Burned-out parents may experience a series of behavioral changes, negatively affecting their children's physical and mental development. This study examined the effects of primary caregivers' parental burnout on adolescents' development and the mediating role of negative parenting styles. This study used a time-lagged design, and data were collected at three different time points. Adolescents were asked to identify their primary caregivers, and parents were asked whether they were the primary caregivers of their children. Thereafter, paired data from the children and primary caregivers were collected. A total of 317 junior middle school students (178 boys, Mage = 14.20 ± 0.8 years) and primary caregivers (71 fathers, Mage = 42.20 ± 4.53 years) from Henan province participated. Primary caregivers' parental burnout was positively associated with negative parenting styles, and negative parenting styles mediated the relationship between parental burnout and adolescent development. From the perspective of prevention-focused interventions, it is necessary to focus on preventing the occurrence of parental burnout. Further, parents should try to avoid using abusive behaviors toward their children and neglecting them.

Toxicity of common biocides used in aquaculture to embryos and larvae of Brachymystax tsinlingensis Li.

Brachymystax tsinlingensis Li is a threatened fish species endemic to China. With the problems of environmental factors and seeding breeding diseases, it is important to further improve the efficiency of seeding breeding and the basis of resource protection. This study investigated the acute toxicity of copper, zinc and methylene blue (MB) on hatching, survival, morphology, heart rate (HR) and stress behaviour of B. tsinlingensis. Eggs (diameter: 3.86 ± 0.07 mm, weight: 0.032 ± 0.004 g) of B. tsinlingensis were selected randomly from artificial propagation and developed from eye-pigmentation-stage embryos to yolk-sac stage larvae (length: 12.40 ± 0.02 mm, weight: 0.03 ± 0.001 g) and exposed to different concentrations of Cu, Zn and MB for 144 h in a series of semi-static toxicity tests. The acute toxicity tests indicated that the 96-h median lethal concentration (LC50 ) values of the embryos and larvae were 1.71 and 0.22 mg l-1 for copper and 2.57 and 2.72 mg l-1 for zinc, respectively, whereas the MB LC50 after 144-h exposure for embryos and larvae were 67.88 and 17.81 mg l-1 , respectively. The safe concentrations of copper, zinc and MB were 0.17, 0.77 and 6.79 mg l-1 for embryos and 0.03, 0.03 and 1.78 mg l-1 for larvae, respectively. Copper, zinc and MB treatments with concentrations greater than 1.60, 2.00 and 60.00 mg l-1 , respectively, led to a significantly low hatching rate and significantly high embryo mortality (P < 0.05), and copper and MB treatments with concentrations greater than 0.2 and 20 mg l-1 led to significantly high larvae mortality (P < 0.05). Exposure to copper, zinc and MB resulted in developmental defects, including spinal curvature, tail deformity, vascular system anomalies and discolouration. Moreover, copper exposure significantly reduced the HR of larvae (P < 0.05). The embryos exhibited an obvious change in behaviour, converting from the normal behaviour of emerging from the membrane head first to emerging tail first, with probabilities of 34.82%, 14.81% and 49.07% under copper, zinc and MB treatments, respectively. The results demonstrated that the sensitivity of yolk-sac larvae to copper and MB was significantly higher than that of embryos (P < 0.05) and that B. tsinlingensis embryos or larvae might be more resistant to copper, zinc and MB than other members of the Salmonidae family, which benefits their resource protection and restoration.

A robust and tunable Luttinger liquid in correlated edge of transition-metal second-order topological insulator Ta2Pd3Te5.

The interplay between topology and interaction always plays an important role in condensed matter physics and induces many exotic quantum phases, while rare transition metal layered material (TMLM) has been proved to possess both. Here we report a TMLM Ta2Pd3Te5 has the two-dimensional second-order topology (also a quadrupole topological insulator) with correlated edge states - Luttinger liquid. It is ascribed to the unconventional nature of the mismatch between charge- and atomic- centers induced by a remarkable double-band inversion. This one-dimensional protected edge state preserves the Luttinger liquid behavior with robustness and universality in scale from micro- to macro- size, leading to a significant anisotropic electrical transport through two-dimensional sides of bulk materials. Moreover, the bulk gap can be modulated by the thickness, resulting in an extensive-range phase diagram for Luttinger liquid. These provide an attractive model to study the interaction and quantum phases in correlated topological systems.

Indoloquinazoline alkaloids suppress angiogenesis and inhibit metastasis of melanoma cells.

Metastasis is the leading cause of cancer-related mortality, targeting angiogenesis emerges as a therapeutic strategy for the treatment of melanoma metastasis. Discovery of new antiangiogenic compounds with specific mechanism of action is still desired. In present study, a bioassay-guidance uncovers the EtOAc extract of a marine-derived fungus Aspergillus clavutus LZD32-24 with significant inhibitory activity against the angiogenesis in Tg (fli1a: EGFP) zebrafish model. Extensive chromatographic fractionation led to the isolation of 48 indoloquinazoline alkaloids, including 21 new analogues namely clavutoines A-U (1-21). Their structures were determined by the spectroscopic data, including the ECD, single crystal X-ray diffraction and quantum chemical calculation for the configurational assignments. Among the bioactive analogues, quinadoline B (QB) showed the most efficacy to suppress the zebrafish vascular outgrowth in zebrafish embryos. QB markedly inhibited the migration, invasion and tube formation with weak cytotoxicity in human umbilical vein endothelial cells (HUVECs). Investigation of the mode of action revealed QB suppressed the ROCK/MYPT1/MLC2/coffin and FAK /Src signaling pathways, and subsequently disrupted actin cytoskeletal organization. In addition, QB reduced the number of new vessels sprouting from the ex vivo chick chorioallantoic membrane (CAM), and inhibited the metastasis of B16F10 melanoma cells in lung of C57BL/6 mice through suppressing angiogenesis. These findings suggest that QB is a potential lead for the development of new antiangiogenic agent to inhibit melanoma metastasis.

Insight into Polishing Slurry and Material Removal Mechanism of Photoassisted Chemical Mechanical Polishing of YAG Crystals.

Yttrium aluminum garnet (YAG) crystals are an important gain medium in thin-sheet solid-state lasers, and their processing quality directly affects the performance of solid-state lasers. But it is difficult to achieve high efficiency and high quality of YAG crystals by traditional chemical mechanical polishing (CMP). In this study, we developed a new polishing slurry for photoassisted chemical mechanical polishing (PCMP) of YAG crystals. The polishing slurry is composed of peroxymonosulfate (PMS), manganese ferrite (MnFe2O4), alumina (Al2O3) abrasives, and deionized water. PCMP is conducted in an ultraviolet (UV) light environment. When employing this polishing slurry for PCMP processing of YAG crystals, the material removal rate (MRR) achieved 250 nm/min and the surface roughness achieved 0.35 nm Sa. The experiments verified that both UV light and MnFe2O4 can effectively activate PMS to produce active free radicals and further enhance the chemical action of the polishing slurry. X-ray photoelectron spectroscopy (XPS) analysis results indicated that active radicals reacted with the surface structure of the crystal and removed the aluminum-oxygen octahedron in large quantities from it. The structural defects reduced the surface hardness of the crystal, which means that active free radicals can modify the crystal surface materials.

Extraction, structural characterization, and antioxidant activity of polysaccharides derived from Arctium lappa L.

Introduction: Arctium lappa L. root has high nutritional and medicinal values and has been identified as a healthy food raw material by the Ministry of Health of the People's Republic of China. Methods: In the present study, an aqueous two-phase system (ATPS) of polyethylene glycol (PEG)-(NH4)2SO4 was used to extract Arctium lappa L. polysaccharides (ALPs) from the Arctium lappa L. roots, the optimal extraction conditions of crude ALPs were optimized by using the single-factor experiment and response surface methodology. The structure and composition of ALPs were determined by fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and high-performance liquid chromatography (HPLC). At the same time, the antioxidant activity of ALPs was investigated by in vitro antioxidant experiment. Results: The optimized extraction parameters for extraction ALPs were as follows: the PEG relative molecular weight of 6,000, a quality fraction of PEG 25%, a quality fraction of (NH4)2SO4 18%, and an extraction temperature of 80°C. Under these conditions, the extraction rate of ALPs could reach 28.83%. FTIR, SEM and HPLC results showed that ALPs were typical acidic heteropolysaccharides and had uneven particle size distribution, an irregular shape, and a rough surface. The ALPs were chiefly composed of glucose, rhamnose, arabinose, and galactose with a molar ratio of 70.19:10.95:11.16:6.90. In addition, the ALPs had intense antioxidant activity in vitro with IC50 values in the ·OH radical (1.732 mg/ml), DPPH radical (0.29 mg/ml), and superoxide anion (0.15 mg/ml) scavenging abilities. Discussion: The results showed that ATPS was an efficient method to extract polysaccharides and could be used for the extraction of other polysaccharides. These results indicated that ALPs had great prospects as a functional food and could be exploited in multiple fields.

Responses of Micropterus salmoides under Ammonia Stress and the Effects of a Potential Ammonia Antidote.

Ammonia is a common environmental limiting factor in aquaculture. To investigate the effects of ammonia stress and explore the protective effect of N-carbamylglutamate (NCG) on Micropterus salmoides (M. salmoides), tissue sections and parameters related to oxidative stress and the inflammatory response in M. salmoides were carried out during the ammonia stress test and feeding test. The results demonstrated that the LC50 for 24 h, 48 h, 72 h, and 96 h under ammonia stress in M. salmoides were 25.78 mg/L, 24.40 mg/L, 21.90 mg/L, and 19.61 mg/L, respectively. Under ammonia stress, the structures of the tissues were damaged, and the GSH content decreased, while the MDA content increased with the increase in stress time and ammonia concentration. The NO content fluctuated significantly after the ammonia nitrogen stress. In the 15-day feeding test, with the increased NCG addition amount and feeding time, the GSH content increased while the MDA and NO contents decreased gradually in the NCG addition groups (NL group: 150 mg/kg; NM group: 450 mg/kg; NH group: 750 mg/kg) when compared with their control group (CK group: 0 mg/kg). In the ammonia toxicology test after feeding, the damage to each tissue was alleviated in the NL, NM, and NH groups, and the contents of GSH, MDA, and NO in most tissues of the NH group were significantly different from those in the CK group. The results suggested that ammonia stress caused tissue damage in M. salmoides, provoking oxidative stress and inflammatory response. The addition of NCG to the feed enhances the anti-ammonia ability of M. salmoides. Moreover, the gill and liver might be the target organs of ammonia toxicity, and the brain and kidney might be the primary sites where NCG exerts its effects. Our findings could help us to find feasible ways to solve the existing problem of environmental stress in M. salmoides culture.

Concise Biosynthesis of Tropone-Containing Spiromaterpenes by a Sesquiterpene Cyclase and a Multifunctional P450 from a Deep-Sea-Derived Spiromastix sp. Fungus.

Spiromaterpenes are a group of rare tropone-containing sesquiterpenes with antineuroinflammatory activity. Herein, we elucidate their biosynthetic pathway in a deep-sea-derived Spiromastix sp. fungus by heterologous expression, biochemical characterization, and incubation experiments. The sesquiterpene cyclase SptA was first characterized to catalyze the production of guaia-1(5),6-diene, and a multifunctional cytochrome P450 catalyzed the tropone ring formation. These results provide important clues for the rational mining of bioactive guaiane-type sesquiterpenes and expand the repertoire of P450 activities to synthesize unique building blocks of natural products.

Mechanical and Acoustic Emission Characteristics of Coal-like Rock Specimens under Static Direct Shear and Dynamic Normal Load.

In underground engineering, shear failure is a common failure type in coal-rock mass under medium and low strain-rate disturbance loads. Analyzing the shear failure mechanical properties of coal-rock mass under dynamic normal load is significant. In order to reveal the influence of disturbance load on the shear mechanical properties of coal rock, a dynamic and static load coupling electro-hydraulic servo testing machine was used to conduct the shear tests of coal-like rock materials under dynamic and constant normal load. The amplitude of dynamic load is 10 kN and the frequency is 5 Hz. The damage process of the specimens was detected by the acoustic emission (AE) detection system. The results imply that the shear failure process of coal-like rock materials under constant normal load can be divided into four stages. The normal disturbance decreased the shear strength of the specimens and increased the shear modulus of the specimens. With the increase in normal load, the influence of disturbance on the shear strength of the specimen decreased. By analyzing the AE parameters, it was found that the dynamic load made the internal damage of the specimen more severe during the shear failure process. The damage variable was calculated by AE cumulative energy, and the damage evolution was divided into three stages. The shear failure mechanism of the specimen was judged by RA (rise time/amplitude) and AF (average frequency). It was found that from the elastic deformation stage to the unstable development fracture stage, the proportion of shear fracture increased. When the dynamic normal load was 10 kN and 30 kN, the fracture was mainly shear fracture; When the dynamic normal load was 50 kN, the fracture was mainly tensile or mixed fracture. The dynamic normal load affects the shear strength and failure mechanism. Therefore, the influence of disturbance load on coal-rock mass strength cannot be ignored in underground engineering.

Study on Mechanical Properties and Weakening Mechanism of Acid Corrosion Lamprophyre.

In order to study the weakening mechanism and mechanical behaviors of hard lamprophyre of Carboniferous Permian coal-bearing strata in China's mining area, lamprophyre samples were subjected to static rock dissolution experiments with pH values of 0, 2, and 4. The acid corrosion mechanism of lamprophyre was revealed from the weight changes of samples, characteristics of solution ion concentration, and macro-mechanical properties. The experimental results show that reaction occurred between lamprophyre and acid solution. With the increasing concentration of H+, the reaction was more intense, the degree of acid etching was higher, and the weight loss was greater. The internal damage induced by acid etching results in the slow extension of the compaction stage of stress-strain curve of uniaxial compression, and the obvious deterioration of mechanical properties of the lamprophyre. The uniaxial compressive strength of the lamprophyre in the dry state is 132 MPa, which decreased to 39 MPa under the acid etching condition, showing significant mudding characteristics. Dolomite (CaMg(CO3)2 with 19.63%) and orthoclase (KAlSi3O8 with 31.4%) in lamprophyre are the major minerals constituents involved in acidification reaction. Photomicrograph recorded from SEM studies reveals that the dissolution effect was directly related to the concentration of H+ in the solution. The dissolution effect was from the surface to the inside. The small dissolution pores became larger and continuously expanded, then finally formed a skeleton structure dominated by quartz. The content of K+, Ca2+, and Mg2+ in the solution after acid etching reaction indicates that the acidified product of orthoclase is colloidal H2SiO3, which adhered to the surface of samples during acid etching and hinders the further acidification of minerals. The dissolution of dolomite and orthoclase under acidic conditions directly leads to the damage of their structure and further promotes the water-rock interaction, which is the fundamental reason for the weakening of the mechanical properties of lamprophyre.

Kir2.1-mediated membrane potential promotes nutrient acquisition and inflammation through regulation of nutrient transporters.

Immunometabolism contributes to inflammation, but how activated macrophages acquire extracellular nutrients to fuel inflammation is largely unknown. Here, we show that the plasma membrane potential (Vm) of macrophages mediated by Kir2.1, an inwardly-rectifying K+ channel, is an important determinant of nutrient acquisition and subsequent metabolic reprogramming promoting inflammation. In the absence of Kir2.1 activity, depolarized macrophage Vm lead to a caloric restriction state by limiting nutrient uptake and concomitant adaptations in nutrient conservation inducing autophagy, AMPK (Adenosine 5'-monophosphate-activated protein kinase), and GCN2 (General control nonderepressible 2), which subsequently depletes epigenetic substrates feeding histone methylation at loci of a cluster of metabolism-responsive inflammatory genes, thereby suppressing their transcription. Kir2.1-mediated Vm supports nutrient uptake by facilitating cell-surface retention of nutrient transporters such as 4F2hc and GLUT1 by its modulation of plasma membrane phospholipid dynamics. Pharmacological targeting of Kir2.1 alleviated inflammation triggered by LPS or bacterial infection in a sepsis model and sterile inflammation in human samples. These findings identify an ionic control of macrophage activation and advance our understanding of the immunomodulatory properties of Vm that links nutrient inputs to inflammatory diseases.

Ubiquitination of NLRP3 by gp78/Insig-1 restrains NLRP3 inflammasome activation.

The NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) inflammasome plays a pivotal role in defending the host against infection as well as sterile inflammation. Activation of the NLRP3 inflammasome is critically regulated by a de-ubiquitination mechanism, but little is known about how ubiquitination restrains NLRP3 activity. Here, we showed that the membrane-bound E3 ubiquitin ligase gp78 mediated mixed ubiquitination of NLRP3, which inhibited NLRP3 inflammasome activation by suppressing the oligomerization and subcellular translocation of NLRP3. In addition, the endoplasmic reticulum membrane protein insulin-induced gene 1 (Insig-1) was required for this gp78-NLRP3 interaction and gp78-mediated NLRP3 ubiquitination. gp78 or Insig-1 deficiency in myeloid cells led to exacerbated NLRP3 inflammasome-dependent inflammation in vivo, including lipopolysaccharide-induced systemic inflammation and alum-induced peritonitis. Taken together, our study identifies gp78-mediated NLRP3 ubiquitination as a regulatory mechanism that restrains inflammasome activation and highlights NLRP3 ubiquitination as a potential therapeutic target for inflammatory diseases.

Epithelial Gasdermin D shapes the host-microbial interface by driving mucus layer formation.

Goblet cells and their main secretory product, mucus, play crucial roles in orchestrating the colonic host-microbe interactions that help maintain gut homeostasis. However, the precise intracellular machinery underlying this goblet cell-induced mucus secretion remains poorly understood. Gasdermin D (GSDMD) is a recently identified pore-forming effector protein that causes pyroptosis, a lytic proinflammatory type of cell death occurring during various pathophysiological conditions. Here, we reveal an unexpected function of GSDMD in goblet cell mucin secretion and mucus layer formation. Specific deletion of Gsdmd in intestinal epithelial cells (ΔIEC) led to abrogated mucus secretion with a concomitant loss of the mucus layer. This impaired colonic mucus layer in GsdmdΔIEC mice featured a disturbed host-microbial interface and inefficient clearance of enteric pathogens from the mucosal surface. Mechanistically, stimulation of goblet cells activates caspases to process GSDMD via reactive oxygen species production; in turn, this activated GSDMD drives mucin secretion through calcium ion-dependent scinderin-mediated cortical F-actin disassembly, which is a key step in granule exocytosis. This study links epithelial GSDMD to the secretory granule exocytotic pathway and highlights its physiological nonpyroptotic role in shaping mucosal homeostasis in the gut.

MKRN2 inhibits the proliferation of gastric cancer by downregulating PKM2.

Cumulative evidence suggests that dysfunction of ubiquitinating enzymes is responsible for multiple types of diseases including cancer. However, what role the ubiquitinating enzyme plays in gastric cancer remains unknown. In this study, using bioinformatics analysis and a series of experimental analyses, we found that an E3 ubiquitin-protein, MKRN2 was down-regulated in gastric cancer tissues. Kaplan-Meier survival analysis showed the low MKRN2 expression significantly indicated poor prognosis. Overexpression of MKRN2 notably inhibited cell proliferation in vitro and in vivo. Conversely, knockdown of MKRN2 had the opposite effects in vitro. Additionally, the mechanical analysis indicated that MKRN2 promoted ubiquitination-mediated degradation of PKM2 and attenuated its effect on ERK. Overall, the present study suggests that MKRN2 may be a potential therapeutic target for gastric cancer.

AKT controls NLRP3 inflammasome activation by inducing DDX3X phosphorylation.

The NLRP3 inflammasome, a critical component of the innate immune system, induces caspase-1 activation and interleukin-1ß maturation and drives cell fate toward pyroptosis. However, the mechanism of NLRP3 inflammasome activation still remains elusive. Here we provide evidence that AKT regulates NLRP3 inflammasome activation. Upon NLRP3 activation, AKT activity is inhibited by second stimulus-induced reactive oxygen species. In contrast, AKT activation leads to NLRP3 inhibition and improved mitochondrial fitness. Mechanistically, AKT induces the phosphorylation of the DDX3X (DEAD-box helicase 3, X-linked), a recently identified NLRP3 inflammasome component, and impairs the interaction between DDX3X and NLRP3. Furthermore, an AKT agonist reduces NLRP3-dependent inflammation in two in vivo models of LPS-induced sepsis and Alum-induced peritonitis. Altogether, our study highlights an important role of AKT in controlling NLRP3 inflammasome activation.