Novel 9-Methylanthracene Derivatives as p53 Activators for the Treatment of Glioblastoma Multiforme.

Glioblastoma multiforme, a highly aggressive and lethal brain tumor, is a substantial clinical challenge and a focus of increasing concern globally. Hematological toxicity and drug resistance of first-line drugs underscore the necessity for new anti-glioma drug development. Here, 43 anthracenyl skeleton compounds as p53 activator XI-011 analogs were designed, synthesized, and evaluated for their cytotoxic effects. Five compounds (13d, 13e, 14a, 14b, and 14n) exhibited good anti-glioma activity against U87 cells, with IC50 values lower than 2 µM. Notably, 13e showed the best anti-glioma activity, with an IC50 value up to 0.53 µM, providing a promising lead compound for new anti-glioma drug development. Mechanistic analyses showed that 13e suppressed the MDM4 protein expression, upregulated the p53 protein level, and induced cell cycle arrest at G2/M phase and apoptosis based on Western blot and flow cytometry assays.

Interface-Mediation-Enabled High-Performance Near-Infrared AgAuSe Quantum Dot Light-Emitting Diodes.

Near-infrared (NIR) quantum dot (QD) light-emitting diodes (LEDs) (NIR-QLEDs) for recognition and tracking applications underpin the future of night-vision technology. However, the performance of environmentally benign materials and devices has lagged far behind that of their Pb-containing counterparts. In this study, we demonstrate the superior performance of NIR-QLEDs based on efficient AgAuSe QDs with contact interface mediation. Consequently, we reveal that using cysteamine-treated QD film contact heterointerfaces can effectively eliminate contact defects in devices and preserve their excellent emissive properties. Additionally, the dipole moment orientation of the coordinated additives is inverse of the heterojunction potential difference, simultaneously blocking electrons and enhancing hole injection in operando, optimizing the LED charge injection balance. These devices exhibit a high external quantum efficiency (EQE) and a power conversion efficiency (PCE) of 15.8 and 12.7% at 1046 nm, respectively, a sub-band gap turn-on voltage of 0.9 V, and a low current density (over 10% of the EQE from 0.0017 to 0.31 mA cm-2). These are the highest EQE and PCE values ever reported for environmentally benign NIR-QLEDs. The results of this study can provide a general strategy for the practical application of QDs in electroluminescent devices.

Unveiling the energy transfer mechanism between aqueous colloidal NIR-II quantum dots and water.

Hydrophilic semiconductor quantum dots (QDs) with emission in the second near-infrared window (NIR-II) have been widely studied in bioimaging applications. In such cases, QDs are usually dispersed in water. As is known, water has strong absorbance in the NIR-II region. However, investigations on the interaction between NIR-II emitters and water molecules are ignored in previous studies. Herein, we synthesized a series of mercaptoundecanoic acid-coated silver sulfide (Ag2S/MUA) QDs with various emissions that partially or completely overlapped with the absorbance of water at 1200 nm. By constructing a hydrophobic interface of cetyltrimethylammonium bromide (CTAB) with MUA on the Ag2S QDs surface via forming an ionic bond, significant enhancement of Ag2S QDs photoluminescence (PL) intensity was observed, as well as a prolonged lifetime. These findings suggest that there is an energy transfer between Ag2S QDs and water in addition to the classical resonance absorption. Transient absorption and fluorescence spectra results revealed that the increased PL intensities and lifetime of Ag2S QDs originated from the suppressed energy transfer from Ag2S QDs to the water due to the CTAB bridged hydrophobic interfaces. This discovery is important for a deeper understanding of the photophysical mechanisms of QDs and their applications.

Activatable Rare Earth Near-Infrared-II Fluorescence Ratiometric Nanoprobes.

Rational design of efficient lanthanide-doped down-shifting nanoparticles (DSNPs) has attracted tremendous attention. However, energy loss was inevitable in the multiple Ln3+ doping systems owing to complex energy migration processes. Here, an efficient NaErF4@NaYF4@NaYF4:10%Nd@NaYF4 DSNP was tactfully designed, in which a buffer layer of NaYF4 was modulated to restrict the interionic energy migration between Er3+ and Nd3+; meanwhile, the surface defects were passivated by an outermost layer of NaYF4. Therefore, the as-prepared DSNPs exhibited two intensive near-infrared-II fluorescence emissions of 1525 nm from Er3+ and 1060 nm from doped Nd3+ under 808 nm excitation. Further, a novel ratiometric nanoprobe NaErF4@NaYF4@NaYF4:10%Nd@NaYF4@A1094 was fabricated by coupling an organic dye of A1094 onto the DSNP surface to quench the 1060 nm emission by the efficient Förster resonance energy transfer, while emission at 1525 nm retained. Thereafter, these activatable ratiometric nanoprobes were used for rapid and sensitive detection of peroxynitrite (ONOO-) in vivo.

Colloidal Alloyed Quantum Dots with Enhanced Photoluminescence Quantum Yield in the NIR-II Window.

Semiconductor quantum dots (QDs) with photoluminescence (PL) emission at 900-1700 nm (denoted as the second near-infrared window, NIR-II) exhibit much-depressed photon absorption and scattering, which has stimulated extensive researches in biomedical imaging and NIR devices. However, it is very challenging to develop NIR-II QDs with a high photoluminescence quantum yield (PLQY) and excellent biocompatibility. Herein, we designed and synthesized an alloyed silver gold selenide (AgAuSe) QD with a bright emission from 820 to 1170 nm and achieved a record absolute PLQY of 65.3% at 978 nm emission among NIR-II QDs without a toxic element and a long lifetime of 4.58 µs. It is proved that the high PLQY and long lifetime are mainly attributed to the prevented nonradiative transition of excitons, probably resulted from suppressing cation vacancies and crystal defects from the high mobility of Ag ions by alloying Au atoms. These high-PLQY QDs with nontoxic heavy metal exhibit great application potential in bioimaging, light emitting diodes (LEDs), and photovoltaic devices.

Pb-Doped Ag2 Se Quantum Dots with Enhanced Photoluminescence in the NIR-II Window.

Ag2 Se quantum dots (QDs) as an effective biological probe in the second near-infrared window (NIR-II, 1000-1700 nm) have been widely applied in bioimaging with high tissue penetration depth and high spatiotemporal resolution. However, the ions deficiency and crystal defects caused by the high Ag+ mobility in Ag2 Se crystals are mainly responsible for the inefficient photoluminescence (PL) of Ag2 Se QDs. Herein, a tailored route is reported to achieve controllable doping of Ag2 Se QDs in which Ag is exchanged by Pb via cation exchange (CE), which is unattainable by direct synthetic methods. The Pb-doped Ag2 Se QDs (denoted as Pb:Ag2 Se QDs) present fire-new optical features with significantly enhanced PL intensity of 4.2 folds. Photoelectron spectroscopy confirms that Pb acts as an n-type dopant for Ag2 Se QDs and therefore the electronic impurities provide additional carriers to fill the traps. Moreover, the general validity of this method is demonstrated to convert different sized Ag2 Se into Pb:Ag2 Se QDs, so that a wide range of NIR-II PL with high intensity is obtained. The bright NIR-II emission of Pb:Ag2 Se QDs is further successfully performed in lymphatic system mapping.

Antiosteoclastic bone resorption activity of osteoprotegerin via enhanced AKT/mTOR/ULK1-mediated autophagic pathway.

Autophagy plays a critical role in the maintenance of bone homeostasis. Osteoprotegerin (OPG) is an inhibitor of osteoclast-mediated bone resorption. However, whether autophagy is involved in the antiosteoclastogenic effects of OPG remains unclear. The present study aimed to investigate the potential mechanism of autophagy during OPG-induced bone resorption via inhibition of osteoclasts differentiated from bone marrow-derived macrophages in BALB/c mice. The results showed that after treatment with receptor activator of nuclear factor-κΒ ligand and macrophage colony-stimulating factor for 3 days, TRAP+ osteoclasts formed, representing the resting state of autophagy. These osteoclasts were treated with OPG and underwent autophagy, as demonstrated by LC3-II accumulation, acidic vesicular organelle formation, and the presence of autophagosomes. The levels of autophagy-related proteins, LC3-II increased and P62 decreased at 3 hr in OPG-treated osteoclasts. The viability, differentiation, and bone resorption activity of osteoclasts declined after OPG treatment. Treatment with OPG and chloroquine, an autophagy inhibitor, attenuated OPG-induced inhibition of osteoclastic bone resorption, whereas rapamycin (RAP), an autophagy inducer, enhanced OPG-induced inhibition of differentiation, survival, and bone resorption activity of osteoclasts. Furthermore, OPG reduced the amount of phosphorylated(p) protein kinase B (AKT) and pmTOR and increased the level of pULK, in a dose-dependant manner. LY294002, a phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/AKT pathway inhibitor, attenuated the decline in pAKT, but enhanced the decline in pmTOR and the increase in pULK1 following OPG treatment. RAP enhanced the OPG-induced increase in pULK1. The PI3K inhibitor 3-methyladenine partly blocked OPG-induced autophagy. Thus, the results revealed that OPG inhibits osteoclast bone resorption by inducing autophagy via the AKT/mTOR/ULK1 signaling pathway.

Controlled Synthesis of Ag2 Te@Ag2 S Core-Shell Quantum Dots with Enhanced and Tunable Fluorescence in the Second Near-Infrared Window.

Fluorescence in the second near-infrared window (NIR-II, 900-1700 nm) has drawn great interest for bioimaging, owing to its high tissue penetration depth and high spatiotemporal resolution. NIR-II fluorophores with high photoluminescence quantum yield (PLQY) and stability along with high biocompatibility are urgently pursued. In this work, a Ag-rich Ag2 Te quantum dots (QDs) surface with sulfur source is successfully engineered to prepare a larger bandgap of Ag2 S shell to passivate the Ag2 Te core via a facile colloidal route, which greatly enhances the PLQY of Ag2 Te QDs and significantly improves the stability of Ag2 Te QDs. This strategy works well with different sized core Ag2 Te QDs so that the NIR-II PL can be tuned in a wide range. In vivo imaging using the as-prepared Ag2 Te@Ag2 S QDs presents much higher spatial resolution images of organs and vascular structures as compared with the same dose of Ag2 Te nanoprobes administrated, suggesting the success of the core-shell synthetic strategy and the potential biomedical applications of core-shell NIR-II nanoprobes.

Osteoprotegerin inhibit osteoclast differentiation and bone resorption by enhancing autophagy via AMPK/mTOR/p70S6K signaling pathway in vitro.

Osteoclasts are highly differentiated terminal cells formed by fusion of hematopoietic stem cells. Previously, osteoprotegerin (OPG) inhibit osteoclast differentiation and bone resorption by blocking receptor activator of nuclear factor-κB ligand (RANKL) binding to RANK indirect mechanism. Furthermore, autophagy plays an important role during osteoclast differentiation and function. However, whether autophagy is involved in OPG-inhibited osteoclast formation and bone resorption is not known. To elucidate the role of autophagy in OPG-inhibited osteoclast differentiation and bone resorption, we used primary osteoclast derived from mice bone marrow monocytes/macrophages (BMM) by induced M-CSF and RANKL. The results showed that autophagy-related proteins expression were upregulated; tartrate-resistant acid phosphatase-positive osteoclast number and bone resorption activity were decreased; LC3 puncta and autophagosomes number were increased and activated AMPK/mTOR/p70S6K signaling pathway. In addition, chloroquine (as the autophagy/lysosome inhibitor, CQ) or rapamycin (as the autophagy/lysosome inhibitor, Rap) attenuated osteoclast differentiation and bone resorption activity by OPG treatment via AMPK/mTOR/p70S6K signaling pathway. Our data demonstrated that autophagy plays a critical role in OPG inhibiting osteoclast differentiation and bone resorption via AMPK/mTOR/p70S6K signaling pathway in vitro.

Photo- and Reduction-Responsive Polymersomes for Programmed Release of Small and Macromolecular Payloads.

We report on the preparation of photo- and reduction-responsive diblock copolymers through reversible addition-fragmentation chain transfer (RAFT) polymerization of a coumarin-based disulfide-containing monomer (i.e., CSSMA) using a poly(ethylene oxide) (PEO)-based macroRAFT agent. The resulting amphiphilic PEO- b-PCSSMA copolymers self-assembled into polymersomes with hydrophilic PEO shielding coronas and hydrophobic bilayer membranes. Upon irradiating the polymersomes with visible light (e.g., 430 nm), the coumarin moieties within the bilayer membranes were cleaved with the generation of primary amine groups, which spontaneously underwent inter/intrachain amidation reactions with the ester moieties, thereby tracelessly cross-linking and permeating the bilayer membranes. Notably, this process only gave rise to the release of small molecule payloads (e.g., doxorubicin hydrochloride, DOX) while large molecule encapsulants (e.g., Texas red-labeled dextran, TR-dextran) were retained within the cross-linked polymersomes due to the preservation of the integrity of the vesicular nanostructures. However, cross-linked polymersomes undergo further structural disintegration upon incubation with glutathione (GSH) due to the scission of disulfide linkages, resulting in the release of macromolecular payloads. Thus, dual-stimuli responsive polymersomes with tracelessly cross-linkable characteristics enable sequential release of payloads with spatiotemporal precision, which could be of promising applications in synergistic loading and programmed release of therapeutics.

[Study on Characteristics of Terahertz Spectra of Organic Functional Groups].

Fourier transform infrared (FTIR) was exploited to measure terahertz (THz) spectra in the wave number range of 30-300 cm(-1) for saturated straight chain organic molecules at room temperature. The results reveal that different organic functional groups exhibit different THz spectral characteristics. The absorption peaks of vibration modes of organic crystal lattice locate in high frequency range of THz, while those of vibration modes of intermolecular hydrogen (H) bonds appear in low frequency range of THz. Moreover, a typical absorption peak of intermolecular H bonds caused by saturated straight-chain monohydric alcohol hydroxyl functional groups locates at 57 cm(-1), while a characteristic absorption peak of intermolecular hydrogen bonds caused by triacontanoic acid carboxyl functional groups appears at 74 cm(-1). The intermolecular H bonds not only result in that the THz absorbing abilities of triacontanol and triacontanoic acid are significantly stronger than that of triacontane, but also cause regular red-shift and blue-shift of the THz absorption peaks of triacontanoic acid, as compared with those of triacontanol. In addition, density functional theory (DFT) B3LYP/6-311G(d,p) basis set was employed to simulate the THz spectra of saturated straight-chain alkane, alkanol and acid, respectively. The simulation results indicate that for the organic molecules with stronger intermolecular H bonds, lower consistent degree of the THz spectrum simulated from monomer molecule with the THz spectrum experimentally measured will occur. Moreover, the simulation results of dimer structures agree well with the measured spectra as compared to those simulated from monomer molecule structures. The results presented in this work are of great significance not only to the study of the THz spectral characteristics of other organic functional groups, but also to the clarification of the vibration modes of organic molecules. Particularly, our results are also helpful for clarifying the THz response theory of organics, and for exploiting the applications of organic materials in THz devices.

[Characterization and simulation of far-infrared spectroscopy for saturated monohydric alcohols].

Fourier transform infrared-attenuated total reflection (FTIR-ATR) was employed to measure the far-infrared (FIR) spectra in wavenumbers of 30-300 cm(-1) for six kinds of saturated monohydric alcohols, namely: methanol, ethanol, propanol, isopropanol, butanol and isobutanol. Further analysis of the FIR spectra for these monohydric alcohols with similar chemical structures reveals that absorption peaks are observed obviously for these alcohols in the 30-150 cm(-1) band, whereas not obvious peaks are measured in the 150-300 cm(-1) band. Moreover, it was found that the monohydric alcohols with higher hydroxy concentration possess lower average FIR transmission. In addition, the average FIR transmissions of linear chain monohydric alcohols are higher than those of the branched chain ones. Furthermore, the density functional theory (DFT) B3LYP/6-311G(d,p) basis set was employed to simulate the structures optimization and to calculate the responding frequencies of the methanol monomer and polymer. Simulation result indicates that no absorption peaks are found in the 30-150 cm(-1) band for the methanol monomer molecule, whereas there are obvious absorption peaks for the methanol polymers in the same band. In addition, the simulated absorption peak positions for the methanol polymers are in agreement with those experimentally measured. Both results indicate that the absorption of the methanol in Terahertz (THz) is attributed to the collective vibrations of different kinds of polymer, and that the polymer for methanol is mainly trimmer. This paper not only provides a new way to investigate the responding frequencies of organic molecule in THz band, but also is helpful for the FTIR-ATR study of other organic molecules.

Pathophysiology and Genetic Associations of Varicose Veins: A Narrative Review.

Varicose veins (VVs) have a high prevalence worldwide and have become a major medical burden. Their pathophysiology involves a complex interplay of inflammation and tissue remodeling, and current treatment is limited by its impact on the pathophysiological mechanisms. In addition, despite clear environmental factors, family history is an important risk factor, suggesting a genetic component to the risk of developing VVs. Our understanding of the pathogenesis of these diseases has benefited greatly from the expansion of population genetic studies, from pioneering family studies to large genome-wide association studies; we now find multiple risk loci for each venous disease. This review considers the pathophysiology of VVs, highlighting the current state of genetic knowledge. We also propose future directions for research.

Targeting G-rich sequence to regulate the transcription of murine double minute (MDM) genes in triple-negative breast cancers.

Murine double minute 2 (MDM2) and homologous protein murine double minute X (MDMX) are p53 negative regulators that perform significant driving effects in tumorigenesis, and targeting these oncoproteins has became an efficient strategy in treating cancers. However, the definite antitumor activity and significance ordering of each protein in MDM family is still unclear due to the similar structure and complicated regulation. Herein, we identified two G-rich sequences (G1 and G5) located in the promoter that could assemble the G-quadruplex to respectively inhibit and promote the transcription of the MDM2 and MDMX. Based on this target, we designed and synthesized a novel G-quadruplex ligand A3f and achieved the differentiated regulation of MDM protein. In triple-negative breast cancer (TNBC) cells, A3f could induce MDM2-dependent proliferation arrest and exhibit additive therapeutic effect with MDMX inhibitors. Overall, this study provided a novel strategy to regulate the transcription of MDM genes by targeting certain G-rich sequences, and discovered an active antitumor molecule for use in TNBC treatment.

Discovery of N-alkyl-N-benzyl thiazoles as novel TRPC antagonists for the treatment of glioblastoma multiforme.

Glioblastoma multiforme represents a substantial clinical challenge. Transient receptor potential channel (TRPC) antagonists might provide new therapeutic options for this aggressive cancer. In this study, a series of N-alkyl-N-benzoyl and N-alkyl-N-benzyl thiazoles were designed and prepared using a scaffold-hopping strategy and evaluated as TRPC6 antagonists. This resulted in the discovery of 15g, a potent TRPC antagonist that exhibited suitable inhibitory micromolar activities against TRPC3, TRPC4, TRPC5, TPRC6, and TRPC7 and displayed noteworthy anti-glioblastoma efficacy in vitro against U87 cell lines. In addition, 15g featured an acceptable pharmacokinetic profile and exhibited better in vivo potency (25 mg/kg/d) than the frontline therapeutic agent temozolomide (50 mg/kg/d) in xenograft models. Taken together, the TRPC antagonist 15g represents a promising lead compound for developing new anti-glioblastoma agents.

The CXCR4-CXCL12 pathway facilitates the progression of pancreatic cancer via induction of angiogenesis and lymphangiogenesis.

BACKGROUND: This study reports the influence of CXCL12 and its receptor CXCR4 on the progression of pancreatic cancer and illuminates the correlation between the CXCL12/CXCR4 axis and the angiogenesis and lymphangiogenesis of pancreatic adenocarcinoma (PAC). METHODS: A total of 30 patients with pancreatic cancer participated in the current study. The expression of CXCL12 and CXCR4 in cancerous tissues, paracancerous tissues, normal pancreas, and lymph nodes surrounding the pancreas were investigated using real-time PCR and immunohistochemistry, respectively. In addition, we assessed microvessel density (MVD) and microlymphatic vessel density (MLVD) in tumor tissues using immunohistochemistry. RESULTS: CXCL12 expression in tumor tissues was significantly lower than that of paracancerous tissues, normal pancreas, and lymph nodes. In contrast, CXCR4 expression in cancerous tissues was considerably higher than that of normal pancreas. Additionally, a significant correlation between the expression pattern of the CXCL12/CXCR4 axis and clinicopathologic features, such as lymph node metastasis, was identified. Furthermore, we found that CXCL12 expression was significantly associated with MVD but not significantly associated with MLVD, while CXCR4 expression was significantly associated with MLVD but not significantly associated with MVD. CONCLUSIONS: The chemotactic interaction between CXCR4 and its ligand CXCL12 may be a critical event during the progression of pancreatic cancer. The underlying mechanism may be the induction of angiogenesis and lymphangiogenesis regulated by the interaction of CXCL12 and CXCR4.

Au-Doped Ag2 Te Quantum Dots with Bright NIR-IIb Fluorescence for In Situ Monitoring of Angiogenesis and Arteriogenesis in a Hindlimb Ischemic Model.

Fluorescence located in 1500-1700 nm (denoted as the near-infrared IIb window, NIR-IIb) has drawn great interest for bioimaging, owing to its ultrahigh tissue penetration depth and spatiotemporal resolution. Therefore, NIR-IIb fluorescent probes with high photoluminescence quantum yield (PLQY) and stability along with high biocompatibility are urgently pursued. Herein, a novel NIR-IIb fluorescent probe of Au-doped Ag2 Te (Au:Ag2 Te) quantum dots (QDs) is developed via a facile cation exchange method. The Au dopant concentration in the Ag2 Te QDs is tunable from 0% to 10% by controlling the ratio of supplied Au precursor to Ag2 Te QDs, resulting in a wide range of PL emission in the NIR-IIb window and a much-enhanced PL intensity. After surface modification, the Au:Ag2 Te QDs possess bright NIR-IIb emission, high colloidal stability and photostability, and decent biocompatibility. Further, in vivo monitoring of the process of angiogenesis and arteriogenesis in an ischemic hindlimb is successfully performed.

Clinical value of circulating tumor cells for the diagnosis and prognosis of hepatocellular carcinoma (HCC): A systematic review and meta-analysis.

BACKGROUND: To evaluate the clinical value of circulating tumor cell (CTC) detection in peripheral blood for the diagnosis and prognosis of hepatocellular carcinoma (HCC). METHODS: Public databases were searched, and a meta-analysis was performed to determine the specificity, sensitivity, negative- likelihood ratio (NLR) and positive-likelihood ratio (PLR), and diagnostic odds ratio (dOR) of CTC detection for the diagnosis of HCC. Hazard ratios (HRs) and 95% confidence intervals (CIs) were analyzed for the association of CTC detection with overall survival (OS) and HCC recurrence. The Meta-DiSc 1.4 and Review Manager 5.2 software programs were used for statistical analysis. RESULTS: Meta-analysis of 20 studies including 1191 patients showed that the specificity, sensitivity, NLR, PLR, and dOR of CTC testing for HCC diagnosis were 0.60 (95% CI = 0.57-0.63), 0.95 (95%CI = 0.93-0.96), 0.36 (95%CI = 0.28-0.48), 11.64 (95%CI = 5.85-23.14), and 38.94 (95%CI = 18.33-82.75), respectively. Meta-analysis of 18 studies including 1466 patients indicated that the OS of CTC-positive HCC patients was less than that of CTC-negative patients (HR = 2.31; 95% CI = 1.55-3.42; P < .01). Meta-analysis of 5 studies including 339 patients revealed that the presence of CTCs in peripheral blood significantly increased the risk of HCC recurrence (HR = 3.03, 95% CI = 1.89-4.86; P < .01). CONCLUSION: CTCs in peripheral blood may be a useful marker for HCC diagnosis. In addition, the prognosis of CTC-positive HCC patients was significantly worse than that of CTC-negative HCC patients. Therefore, further studies are warranted to confirm the clinical potential of CTC detection in peripheral blood in patients with primary HCC.

Two Vanadium(V) Complexes Derived from Bromo and Chloro-Substituted Hydrazone Ligands: Syntheses, Crystal Structures and Antimicrobial Property.

Two vanadium(V) complexes derived from the bromo and chloro-substituted hydrazones N'-(4-bromo-2-hydroxybenzylidene)- 2-chlorobenzohydrazide (H2L1) and N'-(3-bromo-5-chloro-2-hydroxybenzylidene)-3-methylbenzohydrazide (H2L2) with the formula [VOL1(OCH3)(CH3OH)] (1) and [VOL2(OCH3)(CH3OH)] (2) were newly synthesized and characterized by IR, UV-Vis and 1H NMR spectroscopy. The structures of H2L1 and the complexes were further confirmed by single crystal X-ray diffraction. Both vanadium complexes are mononuclear, with the metal atoms coordinated by the hydrazone ligands, methanol ligands, and methanolate ligands, and the oxo groups, forming octahedral geometry. The hydrazones and the vanadium complexes were assayed for the antimicrobial activities on Bacillus subtilis, Staphylococcus aureus, Escherichia coli, and Pseudomonas fluorescence, and the fungi Candida albicans and Aspergillus niger. The existence of the bromo and chloro groups in the hydrazone ligands may improve the antimicrobial property.

Myeloid related protein 8/14 is a new candidate biomarker and therapeutic target for abdominal aortic aneurysm.

Open surgical or percutaneous endovascular (EVAR) intervention is the only approved treatment for abdominal aortic aneurysm (AAA). Novel targeted therapy and companion diagnostic are needed. Our study aimed to investigate the expression of myeloid related protein 8/14 (MRP8/14) in AAA and explore whether MRP8/14 can be a biomarker and therapeutic target for AAA. The serum levels of MRP8/14 and inflammatory factors including TNF-α, IL-1ß, and IL-6 were increased in 20 human AAA patients compared to healthy people by ELISA assay. The mRNA and protein expressions of MRPs in AAA tissues of AAA patient were significantly elevated when compared with the levels in adjacent non-aneurysmal aortic segments in AAA patients. through PCR and western blot analysis. Correlation analysis and receiver operating characteristic (ROC) curve analysis confirmed that MRP8/14 was secreted into the serum and possessed the potential diagnostic value. Rat AAA models established by perfusion porcine pancreatic elastase and murine macrophage RAW264.7 cells were used to evaluate the mechanisms of MRP8/14 after treatment with antibodies. Similarly, MRP8, MRP14, and MRP8/14 were highly expressed in rat AAA model, while the administrations of antibodies of MRPs significantly reversed the improvement expressions of MRP8 and MRP14. In RAW264.7 cells, MRPs especially for MRP8/14 obviously increased the levels of MMP-2 and MMP-9. Under MRP8/14 stimulation, the antibodies of MRPs recovered the expressions of MMP-2 and MMP-9. Anti MRP8/14 antibody exhibited the strongest effect in the experiments. Our results indicated that MRP8/14 was associated with AAA presence and progression and could be considered as a biomarker for AAA diagnose. Anti MRP8/14 can be a potential therapeutic target for treatment of AAA.