KAT7 enhances the proliferation and metastasis of head and neck squamous carcinoma by promoting the acetylation level of LDHA.

Lysine acetyltransferase 7 (KAT7), a histone acetyltransferase, has recently been identified as an oncoprotein and has been implicated in the development of various malignancies. However, its specific role in head and neck squamous carcinoma (HNSCC) has not been fully elucidated. Our study revealed that high expression of KAT7 in HNSCC patients is associated with poor survival prognosis and silencing KAT7 inhibits the Warburg effect, leading to reduced proliferation, invasion, and metastatic potential of HNSCC. Further investigation uncovered a link between the high expression of KAT7 in HNSCC and tumor-specific glycolytic metabolism. Notably, KAT7 positively regulates Lactate dehydrogenase A (LDHA), a key enzyme in metabolism, to promote lactate production and create a conducive environment for tumor proliferation and metastasis. Additionally, KAT7 enhances LDHA activity and upregulates LDHA protein expression by acetylating the lysine 118 site of LDHA. Treatment with WM3835, a KAT7 inhibitor, effectively suppressed the growth of subcutaneously implanted HNSCC cells in mice. In conclusion, our findings suggest that KAT7 exerts pro-cancer effects in HNSCC by acetylating LDHA and may serve as a potential therapeutic target. Inhibiting KAT7 or LDHA expression holds promise as a therapeutic strategy to suppress the growth and progression of HNSCC.

The role of amino acid metabolism in autoimmune hepatitis.

Autoimmune hepatitis (AIH) is an inflammatory chronic liver disease with persistent and recurrent immune-mediated liver injury. The exact cause of AIH is still not fully understood, but it is believed to be primarily due to an abnormal activation of the immune system, leading to autoimmune injury caused by the breakdown of autoimmune tolerance. Although the pathogenesis of AIH remains unclear, recent studies have shown that abnormalities in amino acid metabolism play significant roles in its development. These abnormalities in amino acid metabolism can lead to remodeling of metabolic processes, activation of signaling pathways, and immune responses, which may present new opportunities for clinical intervention in AIH. In this paper, we first briefly outline the recent progress of clinically relevant research on AIH, focusing on the role of specific amino acid metabolism (including glutamine, cysteine, tryptophan, branched-chain amino acids, etc.) and their associated metabolites, as well as related pathways, in the development of AIH. Furthermore, we discuss the scientific issues that remain to be resolved regarding amino acid metabolism, AIH development and related clinical interventions, with the aim of contributing to the future development of amino acid metabolism-based as a new target for the clinical diagnosis and treatment of AIH.

Catalase (CAT) Gene Family in Oil Palm (Elaeis guineensis Jacq.): Genome-Wide Identification, Analysis, and Expression Profile in Response to Abiotic Stress.

Catalases (CATs) play crucial roles in scavenging H2O2 from reactive oxygen species, controlling the growth and development of plants. So far, genome-wide identification and characterization of CAT genes in oil palm have not been reported. In the present study, five EgCAT genes were obtained through a genome-wide identification approach. Phylogenetic analysis divided them into two subfamilies, with closer genes sharing similar structures. Gene structure and conserved motif analysis demonstrated the conserved nature of intron/exon organization and motifs among the EgCAT genes. Several cis-acting elements related to hormone, stress, and defense responses were identified in the promoter regions of EgCATs. Tissue-specific expression of EgCAT genes in five different tissues of oil palm was also revealed by heatmap analysis using the available transcriptome data. Stress-responsive expression analysis showed that five EgCAT genes were significantly expressed under cold, drought, and salinity stress conditions. Collectively, this study provided valuable information on the oil palm CAT gene family and the validated EgCAT genes can be used as potential candidates for improving abiotic stress tolerance in oil palm and other related crops.

The µ-opioid receptor-mediated Gi/o protein and ß-arrestin2 signaling pathways both contribute to morphine-induced side effects.

The µ-opioid receptor-biased agonist theory holds that Gio protein signaling mediates the analgesic effect of opioids and the related side effects via the ß-arrestin2 signaling pathway. A series of µ-opioid-biased agonists have been developed in accordance with this theory, and the FDA has approved TRV130 (as a representative of biased agonists) for marketing. However, several reports have raised the issue of opioid side effects associated with the use of agonists. In this study, five permeable peptides were designed to emulate 11 S/T phosphorylation sites at the µ-opioid receptor (MOR) carboxyl-terminal. In vitro experiments were performed to detect the activation level of G proteins from the cAMP inhibition assay and the ß-arrestin2 recruitment by the BRET assay. Designed peptides might effectively interfere with the activation of the Gio and ß-arrestin2 pathways when combined with morphine. The resulting morphine-induced tolerance, respiratory inhibition, and constipation in mice showed that the ß-arrestin2 pathway was responsible for morphine tolerance while the Gio signaling pathway was involved with respiratory depression and constipation and that these side effects were significantly related to phosphorylation sites S363 and T370. This study may provide new directions for the development of safer and more effective opioid analgesics, and the designed peptides may be an effective tool for exploring the mechanism by which µ-opioid receptors function, with the potential of reducing the side effects that are associated with clinical opioid treatment.

PA suppresses antitumor immunity of T cells by disturbing mitochondrial activity through Akt/mTOR-mediated Ca2+ flux.

Deciphering the mechanisms behind how T cells become exhausted and regulatory T cells (Tregs) differentiate in a tumor microenvironment (TME) will significantly benefit cancer immunotherapy. A common metabolic alteration feature in TME is lipid accumulation, associated with T cell exhaustion and Treg differentiation. However, the regulatory role of free fatty acids (FFA) on T cell antitumor immunity has yet to be clearly illustrated. Our study observed that palmitic acid (PA), the most abundant saturated FFA in mouse plasma, enhanced T cell exhaustion and Tregs population in TME and increased tumor growth. In contrast, oleic acid (OA), a monounsaturated FFA, rescued PA-induced T cell exhaustion, decreased Treg population, and ameliorated T cell antitumor immunity in an obese mouse model. Mechanistically, mitochondrial metabolic activity is critical in maintaining T cell function, which PA attenuated. PA-induced T cell exhaustion and Treg formation depended on CD36 and Akt/mTOR-mediated calcium signaling. The study described a new mechanism of PA-induced downregulation of antitumor immunity of T cells and the therapeutic potential behind its restoration by targeting PA.

Amplified Targeted Drug Delivery Independent of Target Number through Alternative Administration of Two Matched Nanoparticles.

Targeting nanoparticles (NPs) based on the specific binding of ligands with molecular targets provides a promising tool for tissue-selective drug delivery. However, the number of molecular targets on the cell surface is limited, hindering the number of NPs that can bind and, thus, limiting the therapeutic outcome. Although several strategies have been developed to enhance drug delivery, such as enhancing drug loading and circulation time or increasing the enhanced permeability and retention effect of nanocarriers, none have resolved this issue. Herein, we designed a simple method for amplified and targeted drug delivery using two matched NPs. One NP was aptamer-functionalized to specifically bind to target cells, while the other was aptamer-complementary DNA-functionalized to specifically bind to aptamer-NPs. Alternate administration of the two matched NPs enables their continuous accumulation in the disease site despite their limited molecular targets. As a proof of concept, the method was tested in a breast cancer model and significantly enhanced chemotherapy of tumor cells in vitro and in vivo. The potential applications of this method in a brain injury model were also demonstrated. Overall, the study describes a method for amplified targeted drug delivery independent of the target number.

Upregulated Mitochondrial Dynamics Is Responsible for the Procatabolic Changes of Chondrocyte Induced by α2-Adrenergic Signal Activation.

OBJECTIVE: Activation of sympathetic tone is important for cartilage degradation in osteoarthritis (OA). Recent studies reported that sympathetic signals can affect the mitochondrial function of target cells. It is unknown whether this effect exits in chondrocytes and affects chondrocyte catabolism. The contribution of mitochondrial dynamics in the activation of α2-adrenergic signal-mediated chondrocyte catabolism was investigated in this study. DESIGN: Primary chondrocytes were stimulated with norepinephrine (NE) alone, or pretreated with an α2-adrenergic receptor (Adra2) antagonist (yohimbine) and followed by stimulation with NE. Changes in chondrocyte metabolism and their mitochondrial dynamics were investigated. RESULTS: We demonstrated that NE stimulation induced increased gene and protein expressions of matrix metalloproteinase-3 and decreased level of aggrecan by chondrocytes. This was accompanied by upregulated mitochondriogenesis and the number of mitochondria, when compared with the vehicle-treated controls. Mitochondrial fusion and fission, and mitophagy also increased significantly in response to NE stimulation. Inhibition of Adra2 attenuated chondrocyte catabolism and mitochondrial dynamics induced by NE. CONCLUSIONS: The present findings indicate that upregulation of mitochondrial dynamics through mitochondriogenesis, fusion, fission, and mitophagy is responsible for activation of α2-adrenergic signal-mediated chondrocyte catabolism. The hypothesis that "α2-adrenergic signal activation promotes cartilage degeneration in temporomandibular joint osteoarthritis (TMJ-OA) by upregulating mitochondrial dynamics in chondrocytes" is validated. This represents a new regulatory mechanism in the chondrocytes of TMJ-OA that inhibits abnormal activation of mitochondrial fusion and fission is a potential regulator for improving mitochondrial function and inhibiting chondrocyte injury and contrives a potentially innovative therapeutic direction for the prevention of TMJ-OA.

Amino acid metabolism in tumor: New shine in the fog?

Alterations in amino acid metabolism is closely related to the occurrence of clinical diseases. The mechanism of tumorigenesis is complex, involving the complicated relationship between tumor cells and immune cells in local tumor microenvironment. A series of recent studies have shown that metabolic remodeling is intimately related to tumorigenesis. And amino acid metabolic reprogramming is one of the important characteristics of tumor metabolic remodeling, which participates in tumor cells growth, survival as well as the immune cell activation and function in the local tumor microenvironment, thereby affecting tumor immune escape. Recent studies have further shown that controlling the intake of specific amino acids can significantly improve the effect of clinical intervention in tumors, suggesting that amino acid metabolism is gradually becoming one of the new promising targets of clinical intervention in tumors. Therefore, developing new intervention strategies based on amino acid metabolism has broad prospects. In this article, we review the abnormal changes in the metabolism of some typical amino acids, including glutamine, serine, glycine, asparagine and so on in tumor cells and summarize the relationship among amino acid metabolism, tumor microenvironment and the function of T cells. In particular, we discuss the current issues that need to be addressed in the related fields of tumor amino acid metabolism, aiming to provide a theoretical basis for the development of new strategies for clinical interventions in tumors based on amino acid metabolism reprogramming.

Association of Tooth Loss and Diet Quality with Acceleration of Aging: Evidence from NHANES.

BACKGROUND: Although tooth loss is widely recognized as a typical sign of aging, whether it is associated with accelerated aging, and to what extent diet quality mediates this association are unknown. METHODS: Data were collected from the National Health and Nutrition Examination Survey. The missing tooth counts were recorded as the number of edentulous sites. Phenotypic accelerated aging was calculated using 9 routine clinical chemistry biomarkers and chronological age. Healthy Eating Index 2015 (HEI-2015) score was used to evaluate diet quality. Multivariate logistic regression and linear regression were used to analyze the association between tooth loss and accelerated aging. Mediation analyses were used to examine the mediation role of diet quality in the association. RESULTS: The association between tooth loss and accelerated aging was confirmed. The highest quartile of tooth loss showed a positive association with accelerated aging (ß=1.090; 95% confidence interval, 0.555 to 1.625; P < .001). Diet quality decreased with increase number of missing teeth and showed a negative association with accelerated aging. Mediation analysis suggested that the HEI-2015 score partially mediated the association between tooth loss and accelerated aging (proportion of mediation: 5.302%; 95% confidence interval, 3.422% to 7.182%; P < .001). Plant foods such as fruits and vegetables were considered the key mediating food. CONCLUSIONS: The association between tooth loss and accelerated aging, as well as the partially mediating role of dietary quality in this association was confirmed. These findings suggested that more attention should be paid to the population with severe tooth loss and the changes of their dietary quality.

BPOZ-2 is a negative regulator of the NLPR3 inflammasome contributing to SARS-CoV-2-induced hyperinflammation.

Introduction: Inflammation play important roles in the initiation and progression of acute lung injury (ALI), acute respiratory distress syndrome (ARDS), septic shock, clotting dysfunction, or even death associated with SARS-CoV-2 infection. However, the pathogenic mechanisms underlying SARS-CoV-2-induced hyperinflammation are still largely unknown. Methods: The animal model of septic shock and ALI was established after LPS intraperitoneal injection or intratracheal instillation. Bone marrow-derived macrophages (BMDMs) from WT and BPOZ-2 KO mouse strains were harvested from the femurs and tibias of mice. Immunohistology staining, ELISA assay, coimmunoprecipitation, and immunoblot analysis were used to detect the histopathological changes of lung tissues and the expression of inflammatory factors and protein interaction. Results and conclusions: We show a distinct mechanism by which the SARS-CoV-2 N (SARS-2-N) protein targets Bood POZ-containing gene type 2 (BPOZ-2), a scaffold protein for the E3 ubiquitin ligase Cullin 3 that we identified as a negative regulator of inflammatory responses, to promote NLRP3 inflammasome activation. We first demonstrated that BPOZ-2 knockout (BPOZ-2 KO) mice were more susceptible to lipopolysaccharide (LPS)-induced septic shock and ALI and showed increased serum IL-1ß levels. In addition, BMDMs isolated from BPOZ-2 KO mice showed increased IL-1ß production in response to NLRP3 stimuli. Mechanistically, BPOZ-2 interacted with NLRP3 and mediated its degradation by recruiting Cullin 3. In particular, the expression of BPOZ-2 was significantly reduced in lung tissues from mice infected with SARS-CoV-2 and in cells overexpressing SARS-2-N. Importantly, proinflammatory responses triggered by the SARS-2-N were significantly blocked by BPOZ-2 reintroduction. Thus, we concluded that BPOZ-2 is a negative regulator of the NLPR3 inflammasome that likely contributes to SARS-CoV-2-induced hyperinflammation.

Design and synthesis of novel GluN2A NMDAR positive allosteric modulators via scaffold hopping strategy as anti-stroke therapeutic agents.

NMDA receptor subunits have differential roles in mediating excitotoxic neuronal death both in vitro and in vivo . Activation of NR2A-containing NMDA receptors promotes neuronal survival and exerts a neuroprotective action, whereas over activating GluN2B-containing receptor results in excitotoxicity, increasing neuronal apoptosis. Our previous study has identified Npam 43 as a NMDAR positive allosteric modulators. However, the cis-trans isomerization impedes the development of Npam 43 as potential neuroprotective agents. To discover more potent and selective GluN2A NMDAR positive allosteric modulators, 38 derivatives were synthesized and evaluated their neuroprotective effect on glutamate-exposed PC-12 cells. The allosteric activities of compounds were evaluated using calcium imaging approaches. Among them, compound 5c exhibit GluN1/2A selectivity over GluN1/2B and show neuroprotective activity in vitro and in vivo. This study reported a series of GluN1/2A positive allosteric modulators as neuroprotective agents, and provided a potential opportunity to discover new drugs for stroke treatment.

The effectiveness of warming approaches in preventing perioperative hypothermia: Systematic review and meta-analysis.

AIM: To assess if experimental warming interventions are superior to routine warming interventions in preventing perioperative hypothermia. BACKGROUND: Perioperative hypothermia is a critical issue for the complications of surgery. There are various kinds of perioperative warming interventions, including experimental and routine warming interventions. METHODS: We performed a systematic literature review and meta-analysis for the randomized clinical trials of experimental warming interventions vs. routine warming interventions in the perioperative period. FINDINGS: A total of 15 studies were included with 983 participants allocated to experimental warming interventions and 939 controls with routine warming interventions, who were receiving a variety of surgeries. The focused outcome was the intraoperative and postoperative body temperature. All included studies were randomized clinical trials. Among the participants receiving operations, the meta-analysis showed that routine warming intervention groups experienced lower intraoperative and postoperative body temperatures compared to the experimental warming groups. The meta-analysis results included positive mean differences, significant tests for overall effect and significant heterogeneity in the random-effects model. CONCLUSIONS: In spite of significant heterogeneity, experimental warming interventions are likely to demonstrate superior warming effects when compared to routine warming interventions, as shown by the current meta-analysis results of randomized clinical trials.

Corrigendum: Glycemic Control Regimens in the Prevention of Surgical Site Infections: A Meta-Analysis of Randomized Clinical Trials.

[This corrects the article DOI: 10.3389/fsurg.2022.855409.].

Effective dose/duration of natural flavonoid quercetin for treatment of diabetic nephropathy: A systematic review and meta-analysis of rodent data.

BACKGROUND: Given the challenges on diabetic nephropathy (DN) treatment, research has been carried out progressively focusing on dietary nutrition and natural products as a novel option with the objective of enhancing curative effect and avoiding adverse reactions. As a representative, Quercetin (Qu) has proved to be of great value in current data. PURPOSE: We aimed to synthetize the evidence regarding the therapeutic effect and specific mechanism of quercetin on DN via systematically reviewing and performing meta-analysis. METHODS: Preclinical literature published prior to August 2021, was systematical retrieval and manually filtrated across four major databases including PubMed, Web of Science, EMBASE and Cochrane library. Pooled overall effect sizes of results were generated by STATA 16.0, and underlying mechanisms were summarized. Three-dimensional dose/time-effect analyses and radar maps were conducted to examine the dosage/time-response relations between Qu and DN. RESULTS: This paper pools all current available evidence in a comprehensive way, and shows the therapeutic benefits as well as potential action mechanisms of Qu in protecting the kidney against damage. A total of 304 potentially relevant citations were identified, of which 18 studies were enrolled into analysis. Methodological quality was calculated, resulting in an average score of 7.06/10. This paper provided the preliminary evidence that consumption of Qu could induce a statistical reduction in mesangial index, Scr, BUN, 24-h urinary protein, serum urea, BG, kidney index, TC, TG, LDL-C, AST, MDA, AGE, TNF-α, TGF-ß1, TGF-ß1 mRNA, CTGF and IL-1ß, whereas HDL-C, SOD, GSH, GSH-Px, CAT and smad-7 were significantly increased. Furthermore, Qu could remarkably improve the renal pathology. In terms of the mechanisms underlying therapy of DN, Qu exerts anti-diabetic nephropathy properties possibly through PI3K/PKB, AMPK-P38 MAPK, SCAP/SREBP2/LDLr, mtROS-TRX/TXNIP/NLRP3/IL-1ß, TGF-ß1/Smad, Nrf2/HO-1, Hippo, mTORC1/p70S6K and SHH pathways. Dose/time-response images predicted a modest association between Qu dosage consumption/administration length and therapeutic efficacy, with the optimal dosage at 90-150 mg/kg/d and administration length ranging from 8 weeks to 12 weeks. CONCLUSIONS: Quercetin exhibit highly pleiotropic actions, which simultaneously contributes to prevent fundamental progression of DN, such as hyperglycemia, dyslipidemia, inflammation, fibrotic lesions and oxidative stress. The therapeutic effect becomes stronger when Qu administration at higher dosages lasts for longer durations. Taken together, quercetin could be used in patients with DN as a promising agent, which has well-established safety profiles and nontoxicity according to existing literature.

Glycemic Control Regimens in the Prevention of Surgical Site Infections: A Meta-Analysis of Randomized Clinical Trials.

Background: Increased risk of surgical site infections (SSIs) caused by hyperglycemia makes it necessary to follow perioperative glucose lowering strategies to reduce postoperative complications. A meta-analysis was conducted to understand the efficacy of intensive vs. conventional blood glucose lowering regimens on the incidence of SSIs and hypoglycemia from various randomized controlled studies (RCTs). Materials and Methods: A systematic literature review was conducted using MEDLINE and Central databases for RCTs that involved intensive (lower blood glucose target levels) vs. conventional (higher blood glucose target levels) strategies in patients undergoing various types of surgeries. The primary outcomes were SSIs or postoperative wound infections. Hypoglycemia and mortality outcomes were also studied. A random-effects model was used to calculate the pooled risk ratio (RR), and subgroup analyses were performed. Results: A total of 29 RCTs were included in the meta-analysis with the information from 14,126 patients. A reduction in overall incidence of SSIs was found (RR 0.63, 0.50-0.80, p = 0.0002, I 2= 56%). Subgroup analyses showed that intensive insulin regimens decreased the risk of SSIs in patients with diabetes, in cardiac and abdominal surgical procedures, and during the intraoperative and postoperative phases of surgery. However, the risk of hypoglycemia and mortality was increased in the intensive group compared to the conventional group. Conclusion: The results of the meta-analysis provide support for the use of intensive insulin regimens during the perioperative phase for decreasing the incidence of SSIs in certain patient populations and surgical categories.

Robust, accurate, and improved measurement of structural deformation based on off-axis digital image correlation.

We propose a noncontact method for measuring structural deformation using off-axis digital image correlation. An efficient and high-precision algorithm that is insensitive to the accuracy of the initial guess is proposed and validated through numerical simulation. Image displacements in pixels are converted to physical displacements in millimeters using a calibration model based on a new method of measuring the objective distance. A new image-based structural deformation measurement system is proposed and validated using laboratory test results. The proposed method is easy to implement and accurate for structural deformation measurements.

Coevolution between Himalayan cuckoos and 2 sympatric Pycnonotidae hosts.

Selection due to cuckoo parasitism is responsible for the evolution of anti-parasitism defenses in hosts. Different host species breeding sympatrically with a single parasitic cuckoo may evolve different strategies to reduce the risk of counter cuckoo parasitism, resulting in different interactions between cuckoos and hosts in areas of sympatry. Here, we studied the coevolutionary interactions between Himalayan cuckoos Cuculus saturatus and 2 sympatric and closely related potential hosts belonging to the family Pycnonotidae, the brown-breasted bulbul Pycnonotus xanthorrhous and the collared finchbill Spizixos semitorques. We investigated parasitism rates and nest-site selection (nest height, nest cover, human disturbance, perch height, forest distance, and degree of concealment) related to parasitism risk, nest defense against a cuckoo dummy, and egg rejection against cuckoo model eggs. Bulbuls used specific nest sites that were further away from forests than those of finchbills, and they behaved more aggressively toward cuckoos than finchbills. In contrast, bulbuls possessed moderate egg rejection ability, whereas the finchbill rejected 100% of cuckoo model eggs. We suggest that selection of a nest site away from forests by the bulbul explains the absence of parasitism by Himalayan cuckoos. We suggest that these interspecific differences in nest-site selection and nest defense indicate alternative responses to selection due to cuckoos.

Impact of nest sanitation behavior on hosts' egg rejection: an empirical study and meta-analyses.

Egg rejection in birds is a specific adaptation toward avian brood parasitism, whereas nest sanitation is a general behavior for cleaning the nest and avoiding predation. However, both behaviors refer to the action of ejecting objects out of the nest, and nest sanitation has been proposed as a pre-adaptation for egg rejection. Here, we tested the eliciting effect of nest sanitation on egg rejection in the red-whiskered bulbul Pycnonotus jocosus, a potential host species that are sympatric with parasitic cuckoos. We conducted meta-analyses of previous studies on both nest sanitation and egg rejection, in order to evaluate the consistency of our conclusions. Our results showed that nest sanitation did not elicit egg rejection in P. jocosus. The conclusions concerning such an eliciting effect from previous studies were mixed, whereas the methodologies were inconsistent, making the studies unsuitable for comparisons. However, the ejection frequency of nest sanitation was consistently higher than the frequency of egg rejection across different host species or populations. These results suggest that nest sanitation, which is an ancient behavior, is more fundamental than egg rejection, but the effect of the former on the latter is complex and needs further study. Standardized methodologies and the integration of behavior, physiology, and modeling may provide better opportunities to explore the relationship between nest sanitation and egg rejection.

Scalable synthesis of multicomponent multifunctional inorganic core@mesoporous silica shell nanocomposites.

Integrating multiple materials with different functionalities in a single nanostructure enables advances in many scientific and technological applications. However, such highly sophisticated nanomaterials usually require complex synthesis processes that complicate their preparation in a sustainable and industrially feasible manner. Herein, we designed a simple general method to grow a mesoporous silica shell onto any combination of hydrophilic nanoparticle cores. The synthetic strategy, based on the adjustment of the key parameters of the sol-gel process for the silica shell formation, allows for the embedment of single, double, and triple inorganic nanoparticles within the same shell, as well as the size-control of the obtained nanocomposites. No additional interfacial adhesive layer is required on the nanoparticle surfaces for the embedding process. Adopting this approach, electrostatically stabilized, small-sized (from 4 to 15 nm) CeO2, Fe3O4, Gd2O3, NaYF4, Au, and Ag cores were used to test the methodology. The mean diameter of the resulting nanocomposites could be as low as 55 nm, with high monodispersity. These are very feasible sizes for biological intervention, and we further observed increased nanoparticle stability in physiological environments. As a demonstration of their increased activity as a result of this, the antioxidant activity of CeO2 cores was enhanced when in core-shell form. Remarkably, the method is conducted entirely at room temperature, atmospheric conditions, and in aqueous solvent with the use of ethanol as co-solvent. These facile and even "green" synthesis conditions favor scalability and easy preparation of multicomponent nanocomposite libraries with standard laboratory glassware and simple benchtop chemistry, through this sustainable and cost-effective fabrication process.

RHOV promotes lung adenocarcinoma cell growth and metastasis through JNK/c-Jun pathway.

Lung adenocarcinoma (LUAD) is a common type of lung cancer with high frequent metastasis and a high death rate. However, genes responsible for LUAD metastasis are still largely unknown. Here, we identify an important role of ras homolog family member V (RHOV) in LUAD metastasis using a combination of bioinformatic analysis and functional experiments. Bioinformatic analysis shows five hub LUAD metastasis driver genes (RHOV, ZIC5, CYP4B1, GPR18 and TCP10L2), among which RHOV is the most significant gene associated with LUAD metastasis. High RHOV expression predicted shorter overall survival in LUAD patients. RHOV overexpression promotes proliferation, migration, and invasion of LUAD cells, whereas RHOV knockdown inhibits these biological behaviors. Moreover, knockdown of RHOV suppresses LUAD tumor growth and metastasis in nude mice. Mechanistically, RHOV activates Jun N-terminal Kinase (JNK)/c-Jun signalling pathway, an important pathway in lung cancer development and progression, and regulates the expression of markers of epithelial-to-mesenchymal transition, a process involved in cancer cell migration, invasion and metastasis. RHOV-induced malignant biological behaviors are inhibited by pyrazolanthrone, a JNK inhibitor. Our findings indicate a critical role of RHOV in LUAD metastasis and may provide a biomarker for prognostic prediction and a target for LUAD therapy.