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Figure S1. PF-03084014 selective inhibits high Notch1 expression HCC cells and does not suppress normal hepatocytes proliferation; Figure S2. Intermittent dosing of PF-03084014 reduced gastrointestinal toxicity; Figure S3. Antitumor effect of PF-03084014 on HCC monolayer cell derived orthotopic tumor; Figure S4. Pretreatment with PF-03084014 in vitro decreased HCC sphere's tumorigenicity in vivo; Figure S5. PF-03084014 inhibits mRNA levels of Notch1, HEY1 and Dll1. mRNA levels of Notch1, HEY1, and DLL1 in 97H spheres treated with PF-03084014 versus DMSO.

Table S1: Primer sequences; Table S2. The association of clinicopathological parameters or Notch1 expression with HCC overall survival and disease-free survival using univariate and multivariate analysis

Supplementary figure legends

Background China has been using inactivated coronavirus disease 2019 (COVID-19) vaccines as primary series and booster doses to protect the population from severe to fatal COVID-19. We evaluated primary and booster vaccine effectiveness (VE) against Omicron BA.2 infection outcomes. Methods This was a 13-province retrospective cohort study of quarantined close contacts of BA.2-infected individuals. Outcomes were BA.2 infection, COVID-19 pneumonia or worse, and severe/critical COVID-19. Absolute VE was estimated by comparison with an unvaccinated group. Results There were 289 427 close contacts ≥3 years old exposed to Omicron BA.2 cases; 31 831 turned nucleic acid amplification test–positive during quarantine, 97.2% with mild or asymptomatic infection, 2.6% with COVID-19 pneumonia, and 0.15% with severe/critical COVID-19. None died. Adjusted VE (aVE) against any infection was 17% for primary series and 22% when boosted. Primary series aVE in adults >18 years was 66% against COVID-19 pneumonia or worse and 91% against severe/critical COVID-19. Booster dose aVE was 74% against pneumonia or worse, and 93% against severe/critical COVID-19. Conclusions Inactivated COVID-19 vaccines provided modest protection from infection, very good protection against pneumonia, and excellent protection against severe/critical COVID-19. Booster doses are necessary to provide strongest protection.

Supplementary Figure Legends 1-4 from Suppression of Epidermal Growth Factor Receptor Signaling by Protein Kinase C-α Activation Requires CD82, Caveolin-1, and Ganglioside

Supplementary Figure 3 from Suppression of Epidermal Growth Factor Receptor Signaling by Protein Kinase C-α Activation Requires CD82, Caveolin-1, and Ganglioside

Supplementary Figure 4 from Suppression of Epidermal Growth Factor Receptor Signaling by Protein Kinase C-α Activation Requires CD82, Caveolin-1, and Ganglioside

Supplementary Figure 1 from Suppression of Epidermal Growth Factor Receptor Signaling by Protein Kinase C-α Activation Requires CD82, Caveolin-1, and Ganglioside

Supplementary Figure 2 from Suppression of Epidermal Growth Factor Receptor Signaling by Protein Kinase C-α Activation Requires CD82, Caveolin-1, and Ganglioside

Purpose Gastric cancer (GC) is a malignant tumour with high mortality, and liver metastasis is one of the main causes of poor prognosis. SLIT- and NTRK-like family member 4 (SLITRK4) plays an important role in the nervous system, such as synapse formation. Our study aimed to explore the functional role of SLITRK4 in GC and liver metastasis. Methods The mRNA level of SLITRK4 was evaluated using publicly available transcriptome GEO datasets and Renji cohort. The protein level of SLITRK4 in the tissue microarray of GC was observed using immunohistochemistry. Cell Counting Kit-8, colony formation, transwell migration assays in vitro and mouse model of liver metastatasis in vivo were performed to investigate the functional roles of SLITRK4 in GC. Bioinformatics predictions and Co-IP experiments were applied to screen and identify SLITRK4-binding proteins. Western blot was performed to detect TrkB-related signaling molecules. Results By comparing primary and liver metastases from GC, SLITRK4 was found to be upregulated in tissues of GC with liver metastasis and to be closely related to poor clinical prognosis. SLITRK4 knockdown significantly abrogated the growth, invasion, and metastasis of GC in vitro and in vivo. Further study revealed that SLITRK4 could interact with Canopy FGF Signalling Regulator 3 (CNPY3), thus enhancing TrkB-related signaling by promoting the endocytosis and recycling of the TrkB receptor. Conclusion In conclusion, the CNPY3-SLITRK axis contributes to liver metastasis of GC according to the TrkB-related signaling pathway. which may be a therapeutic target for the treatment of GC with liver metastasis.

BACKGROUND Hypotension after the induction of anesthesia is known to be associated with various adverse events. The involvement of a series of factors makes the prediction of hypotension during anesthesia quite challenging. AIM To explore the ability and effectiveness of a random forest (RF) model in the prediction of post-induction hypotension (PIH) in patients undergoing cardiac surgery. METHODS Patient information was obtained from the electronic health records of the Second Affiliated Hospital of Hainan Medical University. The study included patients, ≥ 18 years of age, who underwent cardiac surgery from December 2007 to January 2018. An RF algorithm, which is a supervised machine learning technique, was employed to predict PIH. Model performance was assessed by the area under the curve (AUC) of the receiver operating characteristic. Mean decrease in the Gini index was used to rank various features based on their importance. RESULTS Of the 3030 patients included in the study, 1578 (52.1%) experienced hypotension after the induction of anesthesia. The RF model performed effectively, with an AUC of 0.843 (0.808-0.877) and identified mean blood pressure as the most important predictor of PIH after anesthesia. Age and body mass index also had a significant impact. CONCLUSION The generated RF model had high discrimination ability for the identification of individuals at high risk for a hypotensive event during cardiac surgery. The study results highlighted that machine learning tools confer unique advantages for the prediction of adverse post-anesthesia events.

The oriental armyworm, Mythimna separata (Walker) is a serious pest of agriculture that does particular damage to Gramineae crops in Asia, Europe, and Oceania. Metamorphosis is a key developmental stage in insects, although the genes underlying the metamorphic transition in M. separata remain largely unknown. Here, we sequenced the transcriptomes of five stages; mature larvae (ML), wandering (W), and pupation (1, 5, and 10 days after pupation, designated P1, P5, and P10) to identify transition-associated genes. Four libraries were generated, with 22,884, 23,534, 26,643, and 33,238 differentially expressed genes (DEGs) for the ML-vs-W, W-vs-P1, P1-vs-P5, and P5-vs-P10, respectively. Gene ontology enrichment analysis of DEGs showed that genes regulating the biosynthesis of the membrane and integral components of the membrane, which includes the cuticular protein (CP), 20-hydroxyecdysone (20E), and juvenile hormone (JH) biosynthesis, were enriched. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that DEGs were enriched in the metabolic pathways. Of these DEGs, thirty CP, seventeen 20E, and seven JH genes were differentially expressed across the developmental stages. For transcriptome validation, ten CP, 20E, and JH-related genes were selected and verified by real-time PCR quantitative. Collectively, our results provided a basis for further studies of the molecular mechanism of metamorphosis in M. separata.

The pollution characteristics of surface ozone and its response to meteorological factors were studied based on monitoring in July 2019 in Shijiazhuang City, China. Furthermore, the WRF-CMAQ model coupled with O

Melanoma is an aggressive malignancy with a high mortality rate. Signal transducer and activator of transcription 3 (STAT3), an oncoprotein, is considered as an effective target for treating melanoma. Chrysoeriol is a flavonoid compound, and possesses anti-tumor activity in lung cancer, breast cancer and multiple myeloma; while whether it has anti-melanoma effects is still not known. Chrysoeriol has been shown to restrain STAT3 signaling in an inflammation mouse model.In this study, the anti-melanoma effects of chrysoeriol and the involvement of STAT3 signaling in these effects were investigated.CCK8 assays, 5-ethynyl-2'-deoxyuridine (EdU) staining, Annexin V-FITC/PI staining, Western blot analyses of cleaved caspase-9 and wound healing assays were used to study the anti-melanoma effects of chrysoeriol in cell models. A B16F10 melanoma bearing mouse model was used to evaluate the in vivo anti-melanoma effects of chrysoeriol. Indicators of cell proliferation, cell apoptosis and angiogeneis in melanoma tissues were detected by immunohistochemistry (IHC) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. Immune cells in melanoma tissues were analyzed by flow cytometry. STAT3-overactivated cell models were used to investigate the involvement of STAT3 signaling in the anti-melanoma effects of chrysoeriol. Molecular dynamics (MD) simulations and surface plasmon resonance (SPR) assays were conducted to determine whether chrysoeriol binds to Src, an upstream kinase of STAT3.The results of cell experiments showed that chrysoeriol dose-dependently inhibited viability, proliferation and migration of, and induced apoptosis in, A375 and B16F10 melanoma cells. Chrysoeriol inhibited the phosphorylation of STAT3, and downregulated the expression of STAT3-target genes involved in melanoma growth and metastasis. Mouse studies showed that chrysoeriol restrained melanoma growth and tumor-related angiogenesis, and altered compositions of immune cells in melanoma microenvironment. Chrysoeriol also inhibited STAT3 signaling in B16F10 allografts. Chrysoeriol's viability-inhibiting effects were attenuated by over-activating STAT3 in A375 cells. Furthermore, chrysoeriol bound to the protein kinase domain of Src, and suppressed Src phosphorylation in melanoma cells and tissues.This study, for the first time, demonstrates that chrysoeriol has anti-melanoma effects, and these effects are partially due to inhibiting STAT3 signaling. Our findings indicate that chrysoeriol has the potential to be developed into an anti-melanoma agent.

Cadmium (Cd) is a heavy metal that is of great concern in the agroecosystem, because of its toxicity to plants and herbivores. Previous research has suggested that populations of herbivorous insects can be affected by Cd, via disrupting tri-trophic interactions comprising plants, herbivores, and predators. However, there is less understanding of the direct effects of dietary Cd on the life history traits and the detoxification or antioxidant enzyme systems of insects. Here we show that the life history traits of the herbivorous oriental armyworm, Mythimna separata (Walker), can be impacted by Cd. The body mass of larvae was decreased under an artificial diet containing a low (0.15 mg kg -1 ) Cd concentration, but was increased by intermediate (0.30 mg kg -1 ) and high (0.60 mg kg -1 ) concentrations of Cd. In contrast, pupal weight declined under intermediate and high concentrations of Cd compared to either low Cd concentration or the control. When Cd concentrations increased, larvae survival rate and fecundity decreased and the pupation rate and pupal deformity rate increased. Low and intermediate concentrations of Cd extended the length of the larval stage while high concentrations of Cd shortened the larval period. Dietary Cd inhibited the activity of antioxidant enzyme polyphenol oxidase (PPO), but increased acetylcholinesterase (AChE) activity and the activities of detoxifying enzymes carboxylesterase (CarE) and glutathione S -transferase (GST) of third-instar larvae. Overall, our results indicate that for Cd concentration there is a physiological trade-off between its adverse effects on life history traits and elevated detoxification, acetylcholinesterase sensitivity and antioxidation of M. separata , thus representing a potential adaptation strategy.

Background Fibroblast-like synoviocytes (FLS) have cancer cell-like characteristics, such as abnormal proliferation and resistance to apoptosis, and play a pathogenic role in rheumatoid arthritis (RA). Hyperproliferation of RA-FLS that can be triggered by the activation of interleukin-6/signal transducer and activator of transcription 3 (IL-6/STAT3) signaling destructs cartilage and bone in RA patients. Chrysoeriol is a flavone found in medicinal herbs such as Chrysanthemi Indici Flos (the dried capitulum of Chrysanthemum indicum L.). These herbs are commonly used in treating RA. Chrysoeriol has been shown to exert anti-inflammatory effects and inhibit STAT3 signaling in our previous studies. This study aimed to determine whether chrysoeriol inhibits hyperproliferation of RA-FLS, and whether inhibiting STAT3 signaling is one of the underlying mechanisms. Methods IL-6/soluble IL-6 receptor (IL-6/sIL-6R)-stimulated RA-FLS were used to evaluate the effects of chrysoeriol. CCK-8 assay and crystal violet staining were used to examine cell proliferation. Annexin V-FITC/PI double staining was used to detect cell apoptosis. Western blotting was employed to determine protein levels. Results Chrysoeriol suppressed hyperproliferation of, and evoked apoptosis in, IL-6/sIL-6R-stimulated RA-FLS. The apoptotic effect of chrysoeriol was verified by its ability to cleave caspase-3 and caspase-9. Mechanistic studies revealed that chrysoeriol inhibited activation/phosphorylation of Janus kinase 2 (JAK2, Tyr1007/1008) and STAT3 (Tyr705); decreased STAT3 nuclear level and down-regulated protein levels of Bcl-2 and Mcl-1 that are transcriptionally regulated by STAT3. Over-activation of STAT3 significantly diminished anti-proliferative effects of chrysoeriol in IL-6/sIL-6R-stimulated RA-FLS. Conclusions We for the first time demonstrated that chrysoeriol suppresses hyperproliferation of RA-FLS, and suppression of JAK2/STAT3 signaling contributes to the underlying mechanisms. This study provides pharmacological and chemical justifications for the traditional use of chrysoeriol-containing herbs in treating RA, and provides a pharmacological basis for developing chrysoeriol into a novel anti-RA agent.

Angiogenesis plays an important role in the growth and metastasis of solid tumors including melanoma. Inhibiting tumor-associated angiogenesis is a tactic in treating melanoma. Dioscin restrains angiogenesis in colon tumor and has anti-melanoma effects in cell and animal models. In a previous study, we found that dioscin inhibits Src/STAT3 signaling in melanoma cells. Activation of the Src/STAT3 pathway has been shown to promote tumor angiogenesis. This study aimed to determine whether dioscin's anti-melanoma effects is related to inhibiting Src/STAT3 signaling-mediated angiogenesis. In a B16F10 allograft mouse model, we found that dioscin inhibited melanoma growth and angiogenesis. To exclude the impact of tumor growth on angiogenesis, a chicken chorioallantoic membrane (CAM) model was used to verify the anti-angiogenic effect of dioscin. Results showed that dioscin suppressed vessel formation in CAM. To determine if tumor secreted pro-angiogenic cytokines are involved in the anti-angiogenic effect of dioscin, conditioned media from dioscin-treated A375 melanoma cells were used to culture human umbilical vein endothelial cells (HUVECs), and tube formation was monitored. It was observed that the tube formation of HUVECs was inhibited. Mechanistic studies revealed that dioscin inhibited the activation of Src and STAT3, and lowered mRNA and protein levels of STAT3 transcriptionally-regulated genes, in B16F10 melanomas. ELISA assays showed that dioscin decreased the secretion of MMP-2, MMP-9 and VEGF from A375 cells. Over-activation of STAT3 lessened the effects of dioscin in decreasing the secretion of pro-angiogenic cytokines from melanoma cells, and in inhibiting tube formation of HUVECs cultured with conditioned media from melanoma cell cultures. In summary, we for the first time demonstrated that inhibiting Src/STAT3 signaling-mediated angiogenesis is involved in the anti-melanoma effects of dioscin. This study provides further pharmacological groundwork for developing dioscin as an anti-melanoma agent.

Hexanol is a major compound contributing to the off-flavors (the bean-like odor) of soybean derived soymilk. The most effective way to reduce the off-flavors of soymilk is the screening and utilization of soybean cultivars with improved hexanol content. However, no genome-wide genetic analysis for this particular trait has been conducted to date. The objective of the present study was to dissect the genetic basis of hexanol content in soybean seed through genome-wide association analysis (GWAS). A total of 105 soybean accessions were analyzed for hexanol content in a three-year experiments and genotyped by sequencing using the specific locus amplified fragment sequencing (SLAF-seq) approach. A total of 25 724 single nucleotide polymorphisms (SNPs) were obtained with minor allele frequencies (MAF)>5%. GWAS showed that 25 quantitative trait nucleotides (QTNs) were significantly associated with the hexanol concentration in soybean seed. These identified QTNs distributed on different genomic regions of the 15 chromosomes. A total of 91 genes were predicted as candidate genes underlying the seed hexanol level and six candidates were predicted possibly underlying the seed hexanol by gene based association. In this study, GWAS has been proven to be an effective way to dissect the genetic basis of the hexanol concentration in multiple genetic backgrounds. The identified beneficial alleles and candidate genes might be valuable for the improvement of marker-assisted breeding efficiency for low hexanol level and help to explore possible molecular mechanisms underlying hexanol content in soybean seed.

Background: Irritable bowel syndrome (IBS) is reported associated with the alteration of gut microbial composition termed as dysbiosis. However, the pathogenic mechanism of IBS remains unclear, while the studies of Chinese individuals are scarce. This study aimed to understand the concept of dysbiosis among patients with Chinese diarrhea-predominant IBS (IBS-D), as a degree of variance between the gut microbiomes of IBS-D population and that of a healthy population. Methods: The patients with IBS-D were recruited (assessed according to the Rome III criteria, by IBS symptom severity score) from the Outpatient Department of Gastroenterology of Peking University Third Hospital, and volunteers as healthy controls (HCs) were enrolled, during 2013. The 16S rRNA sequences were extracted from fecal samples. Ribosomal database project resources, basic local alignment search tool, and SparCC software were used to obtain the phylotype composition of samples and the internal interactions of the microbial community. Herein, the non-parametric test, Wilcoxon rank-sum test was carried out to find the statistical significance between HC and IBS-D groups. All the P values were adjusted to q values to decrease the error rate. Results: The study characterized the gut microbiomes of Chinese patients with IBS-D, and demonstrated that the dysbiosis could be characterized as directed alteration of the microbiome composition leading to greater disparity between relative abundance of two phyla, Bacteroidetes (Z = 4.77, q = 1.59 × 10-5) and Firmicutes (Z = -3.87, q = 5.83 × 10-4). Moreover, it indicated that the IBS symptom features were associated with the dysbiosis of whole gut microbiome, instead of one or several certain genera even they were dominating. Two genera, Bacteroides and Lachnospiracea incertae sedis, were identified as the core genera, meanwhile, the non-core genera contribute to a larger pan-microbiome of the gut microbiome. Furthermore, the dysbiosis in patients with IBS-D was associated with a reduction of network complexity of the interacted microbial community (HC vs. IBS-D: 639 vs. 154). The disordered metabolic functions of patients with IBS-D were identified as the potential influence of gut microbiome on the host (significant difference with q < 0.01 between HC and IBS-D). Conclusions: This study supported the view of the potential influence of gut microbiome on the symptom of Chinese patients with IBS-D, and further characterized dysbiosis in Chinese patients with IBS-D, thus provided more pathological evidences for IBS-D with the further understanding of dysbiosis. Key words: Irritable bowel syndrome; Gut microbiome; Dysbiosis; Microbial diversity; Community network complexity

We investigate the Aharonov-Bohm (AB) effect in the parallel double-quantum-dot structure, by introducing an additional s-wave superconductor to couple to the quantum dots. It is found that the AB oscillation of the electron tunneling is different from the superconductor-absent result. Meawhile, the local and crossed Andreev reflections exhibit their special oscillation behaviors, with the change of the local magnetic flux. This means that the AB effect plays an important role in manipulating the complicated quantum transport through this system. We believe that this work can be helpful for understanding the AB oscillation in the presence of Andreev reflection processes.

This study used sampling analysis and a CAMx-PSAT coupling model to analyze the components, transmission, and source apportionment of PM

Melanoma is the leading cause of cutaneous malignancy death. BRAF inhibitors (BRAFis) have been developed as target therapies because nearly half of patients with melanoma have activating alterations in the BRAF oncogene. However, the fast-developed resistance to BRAFis limits their treatment efficacy. Understanding the molecular mechanism of resistance is vital to increase the success of clinical treatment. We searched three datasets (GSE42872, GSE52882, and GSE106321) from the Gene Expression Omnibus database, which analyzed the mRNA expression profile of melanoma cells under BRAFis treatment, and the differentially expressed genes were identified. Among all the differentially expressed genes, the increased expression of IRF9 and STAT2 was prominent and verified to be upregulated in BRAFis-treated melanoma cells. Furthermore, IRF9 or STAT2 overexpression led to less sensitivity, whereas IRF9 or STAT2 knockdown increased sensitivity to BRAFis treatment. In a subcutaneous xenograft tumor model, we showed that IRF9 or STAT2 overexpression slowed BRAFis-induced tumor shrinking, but IRF9 or STAT2 knockdown led to BRAFis-induced tumor shrinking more quickly. Interestingly, we discovered that IRF9-STAT2 signaling controlled GSDME-dependent pyroptosis by restoring GSDME transcription. These results suggest that targeting IRF9/STAT2 may lead to more promising effective treatments to prevent melanoma resistance to BRAFis by inducing pyroptosis.

In this paper, a regional emissions inventory of anthropogenic VOCs was established based on the traditional emissions factor method for the Beijing-Tianjin-Hebei (BTH) region, followed by a multidimensional calibration study based on regional satellite remote sensing information for formaldehyde and typical urban ground VOCs. Inventory calculations showed that the VOCs emissions in BTH in 2013, 2015, and 2017 were 2026700, 2073400, and 1934200 tons, respectively, comprising alkanes (29.83% to 30.72%), unsaturated hydrocarbons (16.54% to 17.68%), aromatic hydrocarbons (27.14% to 27.51%), aldehydes (8.75% to 9.52%), ketones (8.13% to 9.04%), and aldehydes and ketones lipids (5.13% to 6.60%). During 2013-2017, the emission of VOCs in Zhangjiakou, Qinhuangdao, and Hengshui increased slightly (1.10% to 1.66% per year); emissions in Xingtai and Handan decreased slightly (-1.46% to -1.12% per year); and emissions in Chengde, Tangshan, Baoding, and Cangzhou were stable. There trends were consistent with the inter-annual trend of satellite-derived HCHO column concentrations. However, in Beijing, Tianjin, Langfang, and Shijiazhuang, annual variations in VOCs emissions (-6.51%, -3.30%, 2.16%, and 0.11% per year) and HCHO column concentrations (-1.17%, 7.19%, -0.24%, and 6.68% per year) were observed, respectively. In the regional VOCs inventory, a good linear correlation (

Objective: Nuclear technology has been widely used in military and civilian fields, and radiotherapy is an effective and common form of treatment for cancer. However, acute radiation disease caused by high doses of radiation is a serious complication. The aim of this study was to investigate the chance of mitigating radiation-triggered hematopoiesis failure using human umbilical cord mesenchymal stem cell (HUCMSC) transplantation. Methods: Umbilical cords were obtained from three full-term female neonatus through cesarean section at Xinqiao Hospital. Bone marrow mesenchymal stem cells (BMSCs) were cultivated as depicted before. Briefly, monocytes were collected from bone marrow blood by means of density separation columns. An acute radiation disease mouse model was established to compare the restoration effect of HUCMSCs and BMSCs transplanted via the tail vein. The hematopoietic stem cell transplantation (HSCT) mouse model was obtained through bone marrow cell transplantation (BMCT) from C57BL/6 mice (H-2b, donor) to female CB6F1 mice (H-2b×d, recipient) after irradiation. The mice were divided into five groups, including control (saline), irradiated (radiation), bone marrow (HSCT, transplanted 1×10(6) BM cells), HUCMSC (transplanted a mixture of 1×10(6) HUCMSCs and 1×10(6) BM cells), and BMSC group (transplanted a mixture of 1×10(6) BMSCs and 1×10(6) BM cells). The blood condition results were used to test the radiation-induced inflammatory reaction, and bone marrow pathological staining (H&E) was used to determine the radiation-induced bone marrow hematopoiesis failure. Results: After radiation, HUCMSC transplantation significantly improved the survival rate. By analyzing the blood condition test, colony formation, and bone marrow pathology, it was found that the HUCMSC group demonstrated significant functional improvements in terms of the recovery from hematopoiesis failure and reduction of inflammatory reaction. Conclusions: HUCMSCs have more advantages over BMSCs in restoring and promoting the recovery of radiation-induced hematopoietic damage, thus having a new therapeutic potential for patients with acute radiation disease.

Based on atmospheric monitoring data and the WRF-CAMx model, this study analyzed the characteristics of air pollution and performed a quantitative assessment of PM

Abnormal scarring is a consequence of dysregulation in the wound healing process, with limited options for effective and noninvasive therapies. Given the ability of spherical nucleic acids (SNAs) to penetrate skin and regulate gene expression within, we investigated whether gold-core SNAs (AuSNAs) and liposome-core SNAs (LSNAs) bearing antisense oligonucleotides targeting transforming growth factor beta 1 (TGF-β1) can function as a topical therapy for scarring. Importantly, both SNA constructs appreciably downregulated TGF-β1 protein expression in primary hypertrophic and keloid scar fibroblasts in vitro. In vivo, topically applied AuSNAs and LSNAs downregulated TGF-β1 protein expression levels and improved scar histology as determined by the scar elevation index. These data underscore the potential of SNAs as a localized, self-manageable treatment for skin-related diseases and disorders that are driven by increased gene expression.

Gastritis can lead to ulcers and the development of gastric cancer. The rhizome of Atractylodes macrocephala Koidz. (Asteraceae), a traditional Chinese medicinal herb, is prescribed for the treatment of gastric disorders, hepatitis and rheumatism. Its bio-active compounds are considered to be particularly effective in this regard. However, the molecular processes of the herb's anti-inflammatory activity remain obscure. This study elucidates a mechanism upon which an ethanolic extract of this herb (Am-EE) exerts anti-inflammation effects in RAW264.7 macrophage cells (RAW cells) stimulated by lipopolysaccharide (LPS) treatment and HCl Ethanol-stimulated gastritis rats.To investigate the anti-gastritis activities of Am-EE and explore the mode of action.Ethanol (95%) was used to prepare Am-EE. The quality of the extract was monitored by HPLC analysis. The in vivo effects of this extract were examined in an HCl Ethanol-stimulated gastritis rat model, while LPS-stimulated RAW cells were used for in vitro assays. Cell viability and nitric oxide (NO) production were observed by MTT and Griess assays. Real-time PCR was used to examine mRNA expression. The PGEHPLC analysis indicates that Am-EE contains atractylenolide-1 (AT-1, 1.33%, w/w) and atractylenolide-2 (AT-2, 1.25%, w/w) (Additional Figure. A1). Gastric tissue damage (induced by HCl Ethanol) was significantly decreased in SD rats following intra-gastric application of 35 mg/kg Am-EE. Indistinguishable to the anti-inflammation effects of 35 mg/kg ranitidine (gastric medication). Am-EE treatment also reduced LPS-mediated nitric oxide (NO) and prostaglandin EOur study illustrates that Am-EE suppresses the Akt/IκBα/NF-κB pathway and exerts an anti-inflammatory effect. These novel conclusions provide a pharmacological basis for the clinical use of the A. macrocephala rhizome in the treatment and prevention of gastritis and gastric cancer.