Loss of cancer-associated fibroblast-derived exosomal DACT3-AS1 promotes malignant transformation and ferroptosis-mediated oxaliplatin resistance in gastric cancer.

AIMS: Long non-coding RNAs (lncRNAs), as one of the components of exosomes derived from cancer-associated fibroblasts (CAFs), exhibit a crucial role in the pathogenesis and chemoresistance of gastric cancer (GC). Herein, we investigated the role and mechanism of a novel lncRNA disheveled binding antagonist of beta catenin3 antisense1 (DACT3-AS1) and its involvement in GC. METHODS: DACT3-AS1 was identified by RNA-sequencing and verified by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The functional role of DACT3-AS1 in GC was evaluated using in vitro and in vivo experiments including Transwell assay, 5-Ethynyl-2'-deoxyuridine (EdU) assay, immunoblotting, and xenograft tumor mouse model. Dual-luciferase reporter assay was performed to assess the association between genes. RESULTS: DACT3-AS1 was downregulated and involved in poor prognosis of patients with GC. The results from both in vitro and in vivo experiments showed that DACT3-AS1 suppressed cell proliferation, migration, and invasion through targeting miR-181a-5p/sirtuin 1 (SIRT1) axis. Additionally, DACT3-AS1 was transmitted from CAFs to GC cells mainly via exosomes. Exosomal DACT3-AS1 alleviated xenograft tumor growth. DACT3-AS1 conferred sensitivity of cancer cells to oxaliplatin through SIRT1-mediated ferroptosis both in vitro and in vivo. CONCLUSIONS: CAFs-derived exosomal DACT3-AS1 is a suppressive regulator in malignant transformation and oxaliplatin resistance. DACT3-AS1 could be used for diagnosis and treatment of GC.

Hollow Core-Shelled Na4Fe2.4Ni0.6(PO4)2P2O7 with Tiny-Void Space Capable Fast-Charge and Low-Temperature Sodium Storage.

Iron-based mixed polyanion phosphate Na4Fe3(PO4)2P2O7 (NFPP) is recognized as a promising cathode for Sodium-ion Batteries (SIBs) due to its low cost and environmental friendliness. However, its inherent low conductivity and sluggish Na+ diffusion limit fast charge and low-temperature sodium storage. This study pioneers a scalable synthesis of hollow core-shelled Na4Fe2.4Ni0.6(PO4)2P2O7 with tiny-void space (THoCS-0.6Ni) via a one-step spray-drying combined with calcination process due to the different viscosity, coordination ability, molar ratios, and shrinkage rates between citric acid and polyvinylpyrrolidone. This unique structure with interconnected carbon networks ensures rapid electron transport and fast Na+ diffusion, as well as efficient space utilization for relieve volume expansion. Incorporating regulation of lattice structure by doping Ni heteroatom to effectively improve intrinsic electron and Na+ diffusion path and energy barrier, which achieves fast charge and low-temperature sodium storage. As a result, THoCS-0.6Ni exhibits superior rate capability (86.4 mAh g-1 at 25 C). Notably, THoCS-0.6Ni demonstrates exceptional cycling stability at -20 °C with a capacity of 43.6 mAh g-1 after 2500 cycles at 5 C. This work provides a universal strategy to design the hollow core-shelled structure with tiny-void space cathode materials for reversible batteries with fast-charge and low-temperature storage features.

Zwitterionic Targeting Doxorubicin -Loaded Micelles Assembled by Amphiphilic Dendrimers with Enhanced Antitumor Performance.

Chemotherapy is the main method of treating malignant tumors in clinical treatment. However, the commonly used chemotherapeutic drugs have the disadvantages of high biological toxicity, poor water solubility, low targeting ability, and high side effects. Zwitterionic micelles assembled by amphiphilic dendrimers modified with zwitterionic groups and targeting ligand should largely overcome these shortcomings. Herein, the zwitterionic group and targeting peptide c(RGDfC) were modified on the surface of generation 2 poly(propylene imine) dendrimers (G2 PPI), which was conjugated with hydrophobic N-(2-mercaptoethyl) oleamide to form amphiphilic dendrimers (PPIMYRC). PPIMYRC self-assembled into micelles with doxorubicin (DOX) loaded in the interior of micelles to prepare DOX-loaded micelles (PPIMYRC-DOX micelles). The PPIMYRC-DOX micelles had great stability in fibrinogen and pH-responsive drug release. Furthermore, PPIMYRC-DOX micelles had higher cellular uptake rates than free DOX, resulting in higher cytotoxicity of PPIMYRC-DOX micelles than that of free DOX. More importantly, PPIMYRC-DOX micelles inhibited tumors much better than free DOX. The tumor inhibition rate of PPIMYRC-DOX micelles was as high as 93%. Taken together, PPIMYRC-DOX micelles were assembled by amphiphilic dendrimers with the zwitterionic and targeting groups, which enhanced the therapeutic effect of DOX and reduced its side effects. The prepared targeting nanodrug has great potential for further application in antitumor therapy.

Development of an Ultrasmall and Biocompatible Platinum Nanozyme Encapsulated by Zwitterionic Dendrimer for Highly Sensitive Detection of Glucose.

Many kinds of noble metal nanoparticles can mimic the peroxidase-like function of horseradish peroxidase, which results in their wide applications in bio-related detection and drug delivery. However, those metal nanoparticles usually have low stability and reduced catalytic activity in biological complex medium. Herein, a zwitterionic peroxidase-like enzyme has been developed, which has high stability in fibrinogen solutions and high sensitivity for glucose detection. Maleic anhydride, cysteamine, and zwitterionic peptide EKEKC (EK-5) were used to modify generation 5 poly(amido amine) dendrimers (G5 PAMAM) to prepare zwitterionic dendrimer G5MEKnC with nonfouling properties. Finally, the G5MEKnC-encapsulated platinum nanoparticles (Ptn-G5MEK50C) were prepared by entrapping the platinum nanoparticles (1.40 nm) in the catalytic centers in the interior of G5MEK50C. Pt55-G5MEK50C showed high stability in the buffer solution and the fibrinogen solution within 4 days. They also displayed high biocompatibility toward HeLa cells based on cytotoxicity results and morphological observations. Furthermore, the catalytic oxidation of 3,3',5,5'-tetramethylbenzidine with H2O2 by Pt55-G5MEK50C followed the Michaelis-Menten equation, which confirmed their peroxidase-like properties. The catalytic mechanism was due to the generation of •OH from H2O2. More importantly, the peroxidase-like ability of Pt55-G5MEK50C was successfully used to establish a method for the determination of glucose concentration with a broad linear range of 1-2000 µM and a low detection limit of 0.1 µM. This method was highly accurate for the determination of glucose concentration in plasma. The zwitterionic dendrimer template enhanced the properties of Pt55-G5MEK50C. Taken together, a new kind of biocompatible nanozyme has been developed and successfully used for the sensitive detection of glucose in bio-related medium.

Heat Shock Protein 27 Enhances SUMOylation of Heat Shock Protein B8 to Accelerate the Progression of Breast Cancer.

Heat shock proteins (HSPs) are emerging as valuable potential molecular targets in breast cancer therapy owing to their diverse functions in cancer cells. This study investigated the potential role of heat shock protein 27 (HSP27, also known as HSPB1) in breast cancer through heat shock protein B8 (HSPB8). The correlation between HSP27 and HSPB8 was identified by using co-immunoprecipitation, immunoprecipitation, and SUMOylation assays. Through gain- and loss-of-function approaches in MCF-7 cells, the effect of HSP27 on HSPB8 expression, SUMOylation level, and protein stability of HSPB8, as well as on cell proliferation, migration, and stemness, was elucidated. A mouse xenograft model of breast cancer cells was established to verify the function of HSP27 in vivo. Results indicate that HSP27 and HSPB8 were highly expressed in breast cancer tissues and MCF-7 cells. HSP27 was also found to induce the SUMOylation of HSPB8 at the 106 locus and subsequently increased its protein stability, which resulted in accelerated proliferation, migration, and stemness of breast cancer cells in vitro along with increased tumor metastasis of breast cancer in vivo. However, these results could be reversed by the knockdown of HSPB8. Overall, HSP27 induces SUMOylation of HSPB8 to promote HSPB8 expression, thereby endorsing proliferation and metastasis of breast cancer cells. This study may provide insight for the development of new targets for breast cancer.

Development of an Integrated High Serum Stability Zwitterionic Polypeptide-Based Nanodrug with Both Rapid Internalization and Endocellular Drug Releasing for Efficient Targeted Chemotherapy.

Chemotherapeutic nanodrugs have to penetrate through many biological barriers before reaching the tumor cells. Thus, high stability of the nanocarrier before reaching tumor cells and fast release of the carried drugs in targeted tumor cells are required. In this work, inspired by the intrinsic zwitterionic surface property, mainly formed by glutamic acid and lysine residues, of the plasma protein surface, the zwitterionic poly(glutamyl lysine-co-aspartic acid-co-cysteine) peptide (P(EK-D-C)) was synthesized for conjugating n-mercaptoalkanoic acid (MA) with different chain lengths on cysteine residues through a disulfide linkage to load hydrophobic doxorubicin (DOX). The results showed that the slightly negative-biased zwitterionic nanodrugs were very stable in both resistance to nonspecific plasma protein adsorption and prevention of premature DOX release at physiological pH 7.4 due to the zwitterionic polypeptide shell and the sharp contrast in polarity between the shell and DOX-loaded core, while they can quickly release the loaded DOX through responding to both low pH values in the endosome/lysosome and high glutathione concentrations in the tumor cell cytoplasm. Furthermore, the enhanced internalization of these nanodrugs led to about 60% higher in vitro cytotoxicity against MCF-7 cells at pH 6.7 than at pH 7.4, whereas the in vitro cytotoxicity of DOX·HCl at pH 6.7 was only 75% of the value at pH 7.4. In vivo results revealed that the stable nanodrugs conjugated with the long hydrophobic 12-mercaptododecanoic acid had higher tumor inhibition rate and lower systematic toxicity on MCF-7 tumor-bearing mice than the less stable nanodrugs conjugated with the short 8-mercaptooctaoic acid and were significantly superior to DOX·HCl. These results indicate that the combination of high stability in circulation and fast release in tumor cells of nanodrugs can enhance high efficacy targeted chemotherapy. This pH/redox-sensitive zwitterionic polypeptide nanocarrier might provide an excellent vehicle for solid tumor treatment.

Peroxidase-Like Platinum Clusters Synthesized by Ganoderma lucidum Polysaccharide for Sensitively Colorimetric Detection of Dopamine.

The sensitive and selective detection of dopamine (DA) is very important for the early diagnosis of DA-related diseases. In this study, we reported the colorimetric detection of DA using Ganoderma lucidum polysaccharide (GLP) stabilized platinum nanoclusters (Ptn-GLP NCs). When Pt600-GLP NCs was added, 3,3',5,5'-tetramethylbenzidine (TMB) was rapidly catalyzed and oxidized to blue oxTMB, indicating the peroxidase-like activity of Pt600-GLP NCs. The catalytic reaction on the substrate TMB followed the Michaelis-Menton kinetics with the ping-pong mechanism. The mechanism of the colorimetric reaction was mainly due to the formation of hydroxyl radical (•OH). Furthermore, the catalytic reaction of Pt600-GLP NCs was used in the colorimetric detection of DA. The linear range for DA was 1-100 µM and the detection limit was 0.66 µM. The sensitive detection of DA using Pt-GLP NCs with peroxidase-like activity offers a simple and practical method that may have great potential applications in the biotechnology field.

Application of trauma time axis management in the treatment of severe trauma patients.

PURPOSE: This study aimed at exploring the application of trauma time axis management in the treatment of severe trauma patients by using the Medicalsystem trauma system. METHODS: We performed a retrospective cohort study involving patients with severe trauma. Patients who were admitted before the application of the Medicalsystem trauma system were divided into before system group; patients who were admitted after the application of the system were divided into after system group. Comparison was made between the two groups. For normally distributed data, means were reported along with standard deviation, and comparisons were made using the independent samples t test. Categorical data were compared using the Chi-square test. The Mann-Whitney U test was used to compare nonparametric variables. RESULTS: There were 528 patients admitted to the study during the study period. There was no significant statistical difference in the time from the start of trauma team to arrive at the resuscitation room between the two groups. The time from arrival at hospital to endotracheal intubation, to ventilator therapy, to blood transfusion, to completion of CT scan, to completion of closed thoracic drainage, to the start of operation, as well as the length of stay in resuscitation room and hospital were significantly lower after the application of the Medicalsystem trauma system. The mortality was decreased by 8.6% in the after system group compared with that in the before system group, but there was no statistical difference. CONCLUSION: The Medicalsystem trauma system can optimize diagnosis and treatment process for trauma patients, and accordingly improve the treatment efficiency and shorten the treatment time. Therefore, the Medicalsystem trauma system deserves further popularization and promotion.

Ce-doped CoP nanoparticles embedded in carbon nanotubes as an efficient and durable catalyst for hydrogen evolution.

In this work, a cerium doped CoP nanoparticles (NPs) embedded in carbon nanotubes (CNTs) for efficient and durable hydrogen evolution was developed. The detailed preparation process was described as the followings. First, cerium was introduced into ZIF-67 to form Ce-doped ZIF-67 by a joint nucleation method. Then, the Ce-doped Co-CNTs was synthesized by carbonization of Ce-doped ZIF-67. During the process, the Co2+ was reduced to form Co NPs and the elegant nanostructure of CNTs was formed by the catalytic effect of Co NPs. Finally, by using Ce-doped Co-CNTs as the precursor, the target catalyst (Ce0.05-doped CoP CNTs) was obtained through a chemical vapour deposition (CVD) process in the presence of NaH2PO2. Results of the transmission electron microscopy (TEM) and scanning electron microscopy (SEM) showed that the target catalyst maintained the original rhombic dodecahedron morphology of ZIF-67 and the CoP NPs were embedded in CNTs and distributed uniformly throughout the catalyst. In electrochemical measurements, the catalyst showed the best performance for HER in 0.5 M H2SO4 solution. The onset potential, Tafel slope, electron transfer resistance (R ct) and double-layer capacitance (C dl) of the target catalyst was 49 mV, 78 mV dec-1, 19.2 Ω and 10.5 mF cm-2, respectively. Meanwhile, the catalyst yielded a current density of 10 mA cm-2 merely at an overpotential of 146 mV. Furthermore, it maintained 90% of the original current density in a chronoamperometry measurement and showed no obvious decay even after 2000 cycles scans in a long-term durability test.

Ultra-small biocompatible jujube polysaccharide stabilized platinum nanoclusters for glucose detection.

The development of noble ultra-small biocompatible Pt nanoclusters (Pt NCs) for glucose detection has been drawing great attention. Herein, ultra-small biocompatible jujube polysaccharide (JP) stabilized platinum nanoclusters (Ptn-JP NCs) are prepared using natural JP as a reducing and solubilizing agent. Ptn-JP NCs were studied for the colorimetric detection of glucose. Ptn-JP NCs (n = 50, 200 and 400) had an average particle diameter of 1-2 nm. Particularly, the measurements of hydrodynamic sizes of Ptn-JP NCs indicated that they maintained good stability in solution for one week. Pt200-JP NCs showed good biocompatibility, and were not toxic against HeLa cells at a high concentration of 400 µg mL-1. Furthermore, Pt200-JP NCs catalyzed the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) with H2O2 to produce blue oxidized TMB (oxTMB). This reaction followed typical Michaelis-Menten kinetics. More importantly, the glucose concentration could be sensitively detected by the color change, and this process was not interfered by other sugars. The linear range for glucose concentration was from 0.01 to 1 mM with a detection limit of 5.47 µM. The glucose concentrations of real samples of serum using Pt200-JP NCs were 9.2, 4.9 and 6.5 mM, respectively. The prepared Ptn-JP NCs have great potential in various biomedical detection methods.

Gold nanoshell-based betulinic acid liposomes for synergistic chemo-photothermal therapy.

A novel synthesis approach is first developed to fabricate a multifunctional smart nanodrug delivery system: gold nanoshell-coated betulinic acid liposomes (AuNS-BA-Lips) mediated by a glutathione. The AuNS-BA-Lips exhibited good size distribution (149.4±2.4nm), preferable photothermal conversion ability and synergistic chemo-photothermal therapy. Additionally, the absorption wavelength of AuNS-BA-Lips showed a significantly red-shifted to near infrared (NIR) region, which can strongly absorbed NIR laser and efficiently convert it into localized heat, thus providing controlled drug release and antitumor thermotherapy. Moreover, the nanocarriers excited by NIR light significantly promoted cell uptake compared to those without irradiation, resulting in an enhanced intracellular drug accumulation. Upon NIR irradiation, the AuNS-BA-Lips showed highly efficient antitumor effects on tumor-bearing mice with an inhibition rate of 83.02%, thus demonstrating a remarkable synergistic therapeutic effect of chemotherapy and thermotherapy. Therefore, this work provides new insight into developing a multifunctional antitumor drug.

Aortic Valve Myxoma in a Young Man: A Case Report and Review of Literature.

Myxoma is the most commonly found cardiac primary tumor. The left atrium is the most common localization of myxoma, followed by the right atrium. However, it is rare in the left and right ventricles. Myxoma originating from cardiac valves is extremely rare. This article presents a case of a 17-year-old male who was admitted due to heart murmur for one year. Transthoracic echocardiography indicated a 1.9 cm round solid mass in the left ventricular outflow tract. Excision surgery and aortic valve replacement were performed in this patient. Histopathology revealed the mass as a myxoma. The aortic valve remains a very rare myxoma localization position. Echocardiography can provide a precise method for myxoma diagnosis. Early excision associated with valve replacement can provide good curative effects.

[Expression of osteopontin splice variant and its clinical significance in gastric cancer].

OBJECTIVE: To investigate the expression of osteopontin (OPN) splice variant mRNA, including the three isoforms OPN-A, OPN-B, and OPN-C, to explore its correlation with clinicopathologic features in gastric cancer, and to elucidate their role in tumor invasion and distant metastasis of gastric cancer. METHODS: The expression of OPN-A, OPN-B and OPN-C mRNA were detected by real-time reverse transcriptase-polymerase chain reaction in 66 gastric cancer tissues. The relationship between the expression of OPN-A, OPN-B and OPN-C mRNA and clinicopathologic features of gastric cancer was analyzed. RESULTS: The expression of OPN-C mRNA in the gastric cancer tissue was 3.21-fold higher than that in peritumoral mucosal tissue, showing a significant difference between them (P < 0.001). OPN-C mRNA expression was correlated with the depth of tumor invasion, tumor diameter, lymph node meatastasis, distant meatastasis and had no correlation with differentiation grades. The low expression of OPN-C mRNA was correlated with long survival benefit (P = 0.03). The expression of OPN-A and OPN-B mRNA had no significant relationship with clinicopathologic features of gastric cancer. CONCLUSIONS: One of the isoform of osteopontin (OPN) OPN-C mRNA is overexpressed in gastric cancer. The overexpression of OPN-C mRNA may reflect the progression and is associated with the prognosis of gastric cancer. OPN-C mRNA may have value as a prognostic biomarker in gastric cancer. However, the expression of OPN-A and OPN-B are not correlated with the progression and metastasis of gastric cancer.

Sodium alginate/gelatin hydrogel spheres loaded with Fructus Ligustri Lucidi essential oil: Preparation, characterization and biological activity.

The application of plant essential oils in the food industry is often hindered by their poor water solubility and high volatilize. Encapsulation has emerged as an effective solution to this problem. This study focuses on the preparation of Fructus Ligustri Lucidi essential oil gel spheres (FEOH) based sodium alginate and gelatin. The optimum formulation for FEOH was established by Box-Behnken Design response surface testing, resulting in a composition of 10 % FEO, 5 % TW20 and 2 % CaCl2. This formulation achieved an encapsulation efficiency of 85.56 %. FTIR and SEM results indicated the successful encapsulation of FEO within the gel spheres. Furthermore, DSC and TGA results showed that encapsulation enhanced the thermal stability of the essential oil. At room temperature, the water content of FEOH exceeded 90 %, and it showed the highest swelling ratio of 62.5 % in an alkaline medium at different pH conditions. The in vitro release behavior showed that FEOH was released up to 85.28 % in oil-based food simulants within 2 h. FEOH showed strong antibacterial activity, with a Minimum Inhibitory Concentration (MIC) of 128 mg/mL against Staphylococcus aureus and 256 mg/mL against Escherichia coli. The gel spheres obtained in this research show significant potential as food preservatives in food matrices.

Acyltransferase zinc finger DHHC-type containing 2 aggravates gastric carcinoma growth by targeting Nrf2 signaling: A mechanism-based multicombination bionic nano-drug therapy.

The significant regulatory role of palmitoylation modification in cancer-related targets has been demonstrated previously. However, the biological functions of Nrf2 in stomach cancer and whether the presence of Nrf2 palmitoylation affects gastric cancer (GC) progression and its treatment have not been reported. Several public datasets were used to look into the possible link between the amount of palmitoylated Nrf2 and the progression and its outcome of GC in patients. The palmitoylated Nrf2 levels in tumoral and peritumoral tissues from GC patients were also evaluated. Both loss-of-function and gain-of-function via transgenic experiments were performed to study the effects of palmitoylated Nrf2 on carcinogenesis and the pharmacological function of 2-bromopalmitate (2-BP) on the suppression of GC progression in vitro and in vitro. We discovered that Nrf2 was palmitoylated in the cytoplasmic domain, and this lipid posttranslational modification causes Nrf2 stabilization by inhibiting ubiquitination, delaying Nrf2 destruction via the proteasome and boosting nuclear translocation. Importantly, we also identify palmitoyltransferase zinc finger DHHC-type palmitoyltransferase 2 (DHHC2) as the primary acetyltransferase required for the palmitoylated Nrf2 and indicate that the suppression of Nrf2 palmitoylation via 2-bromopalmitate (2-BP), or the knockdown of DHHC2, promotes anti-cancer immunity in vitro and in mice model-bearing xenografts. Of note, based on the antineoplastic mechanism of 2-BP, a novel anti-tumor drug delivery system ground 2-BP and oxaliplatin (OXA) dual-loading gold nanorods (GNRs) with tumor cell membrane coating biomimetic nanoparticles (CM@GNRs-BO) was established. In situ photothermal therapy is done using near-infrared (NIR) laser irradiation to help release high-temperature-triggered drugs from the CM@GNRs-BO reservoir when needed. This is done to achieve photothermal/chemical synergistic therapy. Our findings show the influence and linkage of palmitoylated Nrf2 with tumoral and peritumoral tissues in GC patients, the underlying mechanism of palmitoylated Nrf2 in GC progression, and novel possible techniques for addressing Nrf2-associated immune evasion in cancer growth. Furthermore, the bionic nanomedicine developed by us has the characteristics of dual drugs delivery, homologous tumor targeting, and photothermal and chemical synergistic therapy, and is expected to become a potential platform for cancer treatment.

Silver-palladium bimetallic nanoparticles stabilized by elm pod polysaccharide with peroxidase-like properties for glutathione detection and photothermal anti-tumor ability.

Noble metal nanoparticles show good application prospects in biosensors and anti-tumor drug research. Herein, the near-spherical silver­palladium bimetallic nanoparticles supported by elm pod polysaccharide (EPP-AgPd1.5 NPs) were prepared by using the elm pod polysaccharide (EPP). EPP acts as a stabilizer and reducing agent due to its water solubility and weak reducing ability. The particle size of EPP-AgPd1.5 NPs was 33.6 ± 5.5 nm. In addition, EPP-AgPd1.5 NPs had peroxidase-like activity to catalyze 3,3',5,5'-tetramethylbenzidine (TMB) to oxidized TMB by catalyzing H2O2 to OH. Based on the peroxidase-like activity of EPP-AgPd1.5 NPs, a method for detecting glutathione was established, and the detection limit and linear range of glutathione concentration were 0.279 µM and 0-400 µM, respectively. More importantly, the photothermal conversion efficiency of EPP-AgPd1.5 NPs reached 39.7 %, and their inhibition rate in HeLa cells reached 69.9 %. Silver­palladium bimetallic nanoparticles stabilized by EPP had good performance in glutathione detection and anti-tumor drugs.

KBTBD2 promotes proliferation and migration of gastric cancer via activating EGFR signaling pathway.

BACKGROUND: To explore the role of Kelch repeat and BTB (POZ) domain containing 2 (KBTBD2) in Gastric cancer(GC) via studying the level of KBTBD2 and its impact on GC cells and mice model. METHODS: Expression of KBTBD2 in GC was analyzed by analysis of TCGA data, Western blotting and Real-time quantitative polymerasechain reaction (RT-qPCR). The role of KBTBD2 on GC cells proliferation, viability, invasion, migration and apoptosis in vitro were assessed by using western blotting，RT-qPCR，CCK-8, EDU, Colony Formation Assay, Wound healing assay, Transwell, JC-1 mitochondrial membrane potential and flow cytometry assay, respectively. And levels of Bcl-2, BAX, PARP, E-cadherin, Vimentin, N-cadherin, EGFR, SOS1, NROS, BRAF,ERK1/2 and GAPDH were tested by western blotting. Relation of KBTBD2 and epidermal growth factor receptor (EGFR) was predicted by KEGG analysis. KBTBD2 gene GSEA enrichment was analyzed by using R language. Moreover, CCK-8, western blotting, and wound healing assays were used to verify the correlation of KBTBD2 and EGFR pathway. Finally, tumor growth in mice was also investigated. Cells proliferation, migration and apoptosis were detected by Ki67 staining, Tunnel staining and mouse lung metastasis model. RESULTS: KBTBD2 was highly expressed in GC, and was related to poor prognosis. Moreover, silencing KBTBD2 suppressed GC cell proliferation, migration and invasion, while also inhibited the EMT, but promoted apoptosis. At the same time, KBTBD2 overexpression showed opposite results. In addition, KBTBD2 regulated the EGFR pathway. Further, silencing KBTBD2 inhibited tumor growth, cell proliferation and migration but promoted apoptosis in vivo, and KBTBD2 overexpression showed opposite results. CONCLUSIONS: KBTBD2 was highly expressed in GC. KBTBD2 promotes the progress of GC by activating EGFR signal pathway. KBTBD2 may thus be a novel target for treating GC.

Reducing the cytotoxity of poly(amidoamine) dendrimers by modification of a single layer of carboxybetaine.

The surface primary amines of generation five poly(amido amine) (G5 PAMAM) dendrimer were modified by different amounts of carboxybetaine acrylamide (CBAA). As a result, the fully modified molecules (CBAA-PAMAM-20, obtained from the 20:1 molar ratio of CBAA molecules to amino groups in modification solution) show excellent compatibility with protein and cells. CBAA-PAMAM-20 and fibrinogen (Fg) could coexist in solution without forming aggregation, indicating very weak interaction force between CBAA-PAMAM-20 and fibrinogen. CBAA-PAMAM-20 exhibits almost undetectable hemolytic activity, while other partially modified ones cause severe hemolysis and fibrinogen aggregation. Furthermore, the membrane of human umbilical vascular endothelial cell (HUVEC) remains intact after 24 h incubation with CBAA-PAMAM-20. The cytotoxicity assay of HUVEC cells and KB cells also showed that the CBAA-PAMAM-20 was not cytotoxic up to a 2 mg/mL concentration (>90% cell viability). In short, a thin compact layer of zwitterionic carboxybetaine could reduce the cytotoxicity of PAMAM through minimizing the interaction with protein and cell membranes, which suggest that the carboxybetaine-coated PAMAM could be a useful platform for biocompatible carriers to load contrast agents and drugs.

Pd nanoparticles stabilized by bitter gourd polysaccharide with peroxidase properties for H2O2 detection.

The development of nanozymes using noble metal nanoparticles to replace natural peroxidase in bio-related detection has been gain great interest. Noble metal nanoparticles with small size have large specific surface area. However, small noble metal nanoparticles tend to aggregate without stabilizer. In this paper, small Pd nanoparticles (3-6 nm) stabilized by bitter gourd polysaccharide (Pdn-BGP NPs) were prepared by using bitter gourd polysaccharide as reducing agent and stabilizing agent. Pd25-BGP NPs had peroxidase-like catalytic property. And the catalytic kinetics of Pd25-BGP NPs towards substrates conformed to the Michaelis-Menten equation. Furthermore, a method was established to detect H2O2 using Pd25-BGP NPs. The linear range and detection limit of this method was 20-320 µM and 2.04 µM, respectively. Finally, Pd25-BGP NPs had good biocompatibility when the concentration was less than 80 µg/mL. The prepared Pd nanoparticles with high stability showed their good prospect in H2O2 detection.

Biocompatible Palladium Nanoparticles Prepared Using Vancomycin for Colorimetric Detection of Hydroquinone.

Hydroquinone poses a major threat to human health and is refractory to degradation, so it is important to establish a convenient detection method. In this paper, we present a novel colorimetric method for the detection of hydroquinone based on a peroxidase-like Pd nanozyme. The vancomycin-stabilized palladium nanoparticles (Van-Pdn NPs, n = 0.5, 1, 2) were prepared using vancomycin as a biological template. The successful synthesis of Van-Pdn NPs (n = 0.5, 1, 2) was demonstrated by UV-vis spectrophotometry, transmission electron microscopy, and X-ray diffraction. The sizes of Pd nanoparticles inside Van-Pd0.5 NPs, Van-Pd1 NPs, and Van-Pd2 NPs were 2.6 ± 0.5 nm, 2.9 ± 0.6 nm, and 4.3 ± 0.5 nm, respectively. Furthermore, Van-Pd2 NPs exhibited excellent biocompatibility based on the MTT assay. More importantly, Van-Pd2 NPs had good peroxidase-like activity. A reliable hydroquinone detection method was established based on the peroxidase-like activity of Van-Pd2 NPs, and the detection limit was as low as 0.323 µM. Therefore, vancomycin improved the peroxidase-like activity and biocompatibility of Van-Pd2 NPs. Van-Pd2 NPs have good application prospects in the colorimetric detection of hydroquinone.