Latest ArticlesSepsis is the leading cause of death in intensive care unit (ICU), which is caused by deregulated immune responses to pathogens infection. Clinically, sepsis treatment is limited to antibiotics and supportive care, while there still lacks of specific molecular therapy. As a type of immune dysfunction disease, macrophages have been recognized as the key immune cells precipitating in the whole process of sepsis, which is activated into M1-like to trigger various inflammatory responses at early stage whereas polarized into M2-like to cause immunosuppression in later stage. Therefore, great attention has been paid on the design of nanomedicines to regulate the functions of macrophages for etiological treatment of sepsis, by virtue of the unique advantages of nano-drug delivery systems, such as enhanced drug bioavailability, targetability, reduced side-effects. This critical review aims to summarize the recent progress of macrophages-regulating nanoparticles for sepsis therapy. First, the essential roles of macrophages in the development and progression of sepsis have been introduced, including the positive roles of macrophages to combat infections and dysfunction of macrophages to cause body damages. We then focus our main attention to discuss the nanomedicines with different therapeutic mechanisms corresponding to each stage of sepsis, such as infection blockage, inflammation inhibition, immune functions recovery, as well as multifunctional nanomedicines. Finally, a few limitations of current nanomedicines are highlighted, and future perspective are speculated for potential clinical translation, which might pave the way for the development of macrophages-centered nanomedicines for more effective sepsis therapy.
Trauma and neurosurgery often result in dural defects and are followed by serious complications or even death, finding suitable dural replacement materials to repair the defective dura has important clinical significance. Porcine peritoneal acellular matrix (PPAM) is a promising alternative material, but its poor stability makes it difficult to meet the various needs of dural reconstruction. In this work, we developed a novel antibacterial cross-linking agent oxidized quaternized guar gum (OQGG) and used it for the first time to stabilize PPAM to construct a dural mater substitute (OQGG-PPAM). The results showed that 1.5% OQGG-PPAM presented suitable mechanical property as well as good thermal stability and resistance to enzymatic degradation. It also exhibited good antibacterial activity and good anti-leakage ability. Furthermore, 1.5% OQGG-PPAM not only exhibited excellent cell compatibility but also significantly stimulated the secretion of bFGF and VEGF from seeded cells which was convenient for dural remodeling. In vivo experiment, it also exhibited the excellent histocompatibility and good anti-adhesion property. This study showed that OQGG can be used as a novel antibacterial cross-linking reagent for crosslinking natural tissues and 1.5% OQGG-PPAM was a potential candidate material for dura mater substitute.
Rational design of electrode meterials with unique core-shell nanostructures is of great significance for improving the electrochemical performance of supercapacitors. In this work, we prepare several CuCo2O4@Ni-Co-S composite electrodes by a controllable hydrothermal and electrodeposition route. One-dimensional nanowires can shorten the ions transport path, while two-dimensional nanosheets expose many active sites. This enables three-dimensional structured composite with high electrochemical activity. The as-prepared heterostructured materials show a specific of 1048 C/g at 1 A/g. It still maintains 75.6% of initial capacity after 20000 cycles at 10 A/g. The device delivers an energy density of 79.2 Wh/kg when the power density reaches to 2280 W/kg. Moreover, it possesses an excellent mechanical stability after repeated folding at different angles
Berberine (BBR) is the primary alkaloid compound of the heat-clearing traditional Chinese medicine Huanglian (Coptis chinensis) and exerts regulatory effects on energy metabolism. However, the specific targets and molecular mechanisms are not clear. In this paper, the BBR-affected energy metabolism pathway was screened by nontargeted metabolomics, and a BBR-derived photoaffinity labeled (PAL) probe was designed to identify potential targets via a chemical proteomics approach. NDUFV1, a subunit of complex Ⅰ on mitochondria, was identified as a potential target of BBR. In the respiratory chain, BBR suppressed the activity of complex Ⅰ, reduced the electrochemical potential in the mitochondrial intermembrane and inhibited the generation of ATP and heat via competitive binding with NDUFV1. The results illustrated the underlying mechanism of BBR in the downregulation of energy metabolism.
Cancer is the leading cause that threatens human life expectancy due to the lack of effective therapies. Cancer immunotherapy has been explored to improve the body's immune system against cancer and accompanied by promising results in recent years. Interleukin 15 (IL-15), a pleiotropic immunomodulator, is critical for immune cells development and displays great anti-tumor potential in both preclinical and clinical trials. In this study, superagonist IL-15 plasmid (psIL-15) consisting of IL-15Rα-sushi-linker-IL-15 was constructed in order to secret superagonist IL-15 (sIL-15) in tumor site. A gene delivery system through self-assembly by methylated polyethylene glycol-b-polylactic acid-b-methylated polyethylene glycol (mPEG-PLA-mPEG) and 1, 2-dioleoyl-3-trimethylammonium-propane (DOTAP), named DMAM, was designed to deliver psIL-15. Further study showed that DMAM/psIL-15 could successfully deliver psIL-15 to tumor cells and the supernatants of the tumor cells could further stimulate lymphocytes proliferation as well as activation in vitro. Local delivery of DMAM/psIL-15 in animal models demonstrated significant tumor inhibition through enhancing immune cells responses, reducing angiogenesis, promoting tumor cell apoptosis and inhibiting proliferation, with no evidence of system toxicities. These results indicate that DMAM/psIL-15 may be a promising strategy for cancer immunotherapy.
Fluorescence image for accurate tumor label still faces challenges in cancer detection and diagnostics. Emerging evidence is indicating that glucose-regulated protein 78 (GRP78), a stress-inducible protein chaperone, is a great potential biomarker and therapeutic target for cancer. However, currently available probe for image tumor based on GRP78 has not been reported, owning to no obvious strategy in probe design towards this protein. In this paper, a hairpin-shaped peptidyl probe (pepFAM) conjugated with a 5-FAM fluorophore and a dabcyl quencher at both ends was developed, respectively. The probe was designed by performing a traditional fluorescence resonance energy transfer mechanism and employing a GRP78 specifically-binding peptide. Furthermore, the probe was used to specifically image cancer cells, and accurately image xenograft tumors in mice models. The novel fluorescent probe is expected to be a useful tool for the diagnostics of cancer.
A series of α-MnO2 catalysts with various Mn valence states were treated by hydrogen reduction for different periods of time. Their catalytic capacity for formaldehyde (HCHO) oxidation was evaluated. The results indicated that hydrogen reduction dramatically improves the catalytic performance of α-MnO2 in HCHO oxidation. The α-MnO2 sample reduced by hydrogen for 2 h possessed superior activity and could completely oxidize 150 ppm HCHO to CO2 and H2O at 70 ℃. Multiple characterization results illustrated that hydrogen reduction contributed to the production of more oxygen vacancies. The oxygen vacancies on the catalyst surface enhanced the adsorption, activation and mobility of O2 molecules, and thereby enhanced HCHO catalytic oxidation. This study provides novel insight into the design of outstanding MnOx catalysts for HCHO oxidation at low temperature.
In this work, a series of chiral phenethylamine synergistic tricarboxylic acid modified β-cyclodextrin bonded stationary phase for high performance liquid chromatography (HPLC) were synthesized via a simple one-pot synthesis approach. Various racemates (aryl alcohols, flavanones, triazoles, benzoin, etc.) were well separated on the tricarboxylic acid modified chiral stationary phases in both normal and reversed modes with good reproducibility and stability, and the influence of mobile phase composition on resolution (Rs) were deeply investigated. The RSD values of Rs for repeatability and column-to-column were below 1.28% and 3.05%, respectively. Hence, the fabrication of tricarboxylic acid modified chiral stationary phase (CSPs) is a new efficient strategy to improve the application of β-cyclodextrin as CSPs in the field of chromatography.
Efficient determination of tumor exosomes using portable devices is crucial for the establishment of facile and convenient early cancer diagnostic methods. However, it is still challenging to effectively amplify the detection signal to achieve tumor exosomes detection with high sensitivity by portable devices. To address this issue, we developed a portable multi-amplified temperature sensing strategy for highly sensitive detecting tumor exosomes based on multifunctional manganese dioxide/IR780 nanosheets (MnO2/IR780 NSs) nanozyme with high oxidase-like activity and enhanced photothermal performance. Inspiringly, MnO2/IR780 NSs were synthesized via a facile one-step method with mild experimental conditions, which not only exhibited a stronger photothermal effect than that of MnO2 but also showed excellent oxidase-like activity that can catalyze the oxidation of 3, 3′, 5, 5′-tetramethylbenzidine (TMB) to generate TMB oxide (oxTMB) with a robust photothermal property, thus conjoining with MnO2/IR780 NSs to further enhance the temperature signal. The present assay enables highly sensitive determination of tumor exosomes with the detection limit down to 5.1 × 103 particles/mL, which was comparable or superior to those of the most previously reported sensors. Furthermore, detection of tumor exosomes spiked in biological samples was successfully realized. More importantly, our method showed the recommendable portability, robust applicability, and easy manipulation. By taking advantages of these features, this high-performance photothermal sensor offered a promising alternative means for nondestructive early cancer diagnosis and treatment efficacy evaluation.
Palladium-catalyzed non-directed CH functionalization provides an efficient approach for direct functionalization of arenes, but it usually suffers from poor site selectivity, limiting its wide application. Herein, it is reported for the first time that the carboxylic acid ligand of 3, 5-dimethyladamantane-1-carboxylic acid (1-DMAdCO2H) can affect the site selectivity during the CH activation step in palladium-catalyzed non-directed CH functionalization, leading to highly para-selective CH olefination of TIPS-protected phenols. This transformation displayed good generality in realizing various other para-selective CH functionalization reactions such as halogenation, and allylation reactions. A wide variety of phenol derivatives including bioactive molecules of triclosan, thymol, and propofol, were compatible substrates, leading to the corresponding para-selective products in moderate to good yields. A preliminary mechanism study revealed that the spatial repulsion factor between carboxylic acid ligand and bulky protecting group resulted in the selective CH activation at the less sterically hindered para-position. This new model non-directed para-selective CH functionalization can provide a straightforward route for remote site-selective CH activations.
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