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In the present paper, agarose acetate (AGA) nanofibrous membranes containing different weight percentages of β-tricalcium phosphate (β-TCP) were successfully developed through electrospinning. The fibers in the nanofibrous membranes had a rough surface due to the β-TCP particles which were uniformly dispersed within or on the surface of AGA fibers. Rat-bone marrow-derived mesenchymal stem cells (rBMSCs) were cultured on the AGA based nanofibrous membranes while showed a good adhesion and proliferation. It was found that more rBMSCs were differentiated to osteoblast-like cells on the β-TCP containing nanofibrous membranes compared with the single AGA membrane, and more alkaline phosphatase (ALP) and mineralized matrix could be detected when rBMSCs were cultured on the β-TCP containing nanofibrous membranes. The nanofibrous membranes were implanted into Sprague-Dawley (SD) rats for biocompatibility test. Gross examination and histological analysis of the AGA based nanofibrous membranes results showed that there was less inflammatory response. All of experimental results suggested that the AGA based nanofibrous membranes had the great potential application in bone tissue engineering. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a common chronic autoimmune disease and eventually ends in severe disability and death. RA has no cure, but there are some treatments for decreasing the severity of various symptoms. For example, pain management of RA by non-steroidal anti-inflammatory drugs (NSAIDs), neutralization of the inflammatory cytokines (or block their functions) of RA by specific biologics. However, the clinical benefit is limited due to their low permeability and poor bioavailability. Meanwhile, the system toxicity for long-term use of NSAIDs is another focal issue. Herein, degradable biopolymer microneedle patch was designed and synthesized. In this dual drug delivery patch, NSAIDs were encapsulated by polymeric nanoparticles, which were coated by the neutrophil membrane, followed by loaded into the microneedle patch for local transdermal delivery. When applied to the murine models, the microneedle patch gradually dissolves and releases the contained nanoparticles. Coating of neutrophil membrane provides the nanosized NSAIDs with the capability of cytokine binding and inflammatory joint tropism. Based on inflammatory microenvironment regulation by cytokine absorption and cyclooxygenase-2 inhibition, the microneedle shows a significant local anti-inflammatory therapeutic effect on mouse model of collagen-induced arthritis and rat model of adjuvant-induced arthritis. Further development based on this advanced strategy may provide additional therapeutic options for RA treatment. [Display omitted] • A therapeutic nanoparticles-loaded microneedle patch was designed for anti-inflammatory treatment of rheumatoid arthritis. • The microneedle patch allows nonsteroidal anti-inflammatory drugs to be applied to the animals with less systemic toxicity. • Simultaneous delivery of neutrophil membrane enhances the inflammatory tropism and anti-inflammatory effects. • It may provide additional therapeutic options for rheumatoid arthritis treatment. [ABSTRACT FROM AUTHOR]

Nanomaterial-mediated photothermal therapy has shown great potential to fulfill the unmet medical needs for treatment of tumors. In this study, a rod-like gold nanoshell capsule, which can offer both photothermal therapy and chemotherapy, is synthesized and applied for the treatment of melanoma. This nano-platform is made by developing a gold nanoshell on rod-like mesoporous silica nanoparticles with different aspect ratios, and it was found that the aspect ratio significantly influenced the cellular uptake and tumor distribution of the nanoparticles. The gold nanoshell capsules with a moderate aspect ratio are found to be efficiently taken up by melanoma cells and are able to penetrate tumor tissues, resulting in the effective ablation of highly malignant melanomas when used along with mild laser irradiation and a single treatment. This study demonstrates that the optimization of the aspect ratio is indispensable to further development of this nanoplatform for antitumor therapy. From the Clinical Editor The combination of hyperthermia and chemotherapeutic agents has been investigated as a new approach for the treatment of malignant melanoma. It appears that the aspect ratio may play an important role in the treatment efficacy. In this article, the authors studied how the AR influenced the cellular uptake and the optimal AR for antitumor effects. [ABSTRACT FROM AUTHOR]

The imbalance of gut microbiota, such as dysbiotic expansion of Enterobacteriaceae, is strongly associated with the progress of inflammatory bowel disease (IBD) via exacerbating gut inflammation and disturbing intestinal mucosal barrier. Recently, a microbiota-based strategy is an attractive paradigm for IBD therapy. Here, we explored the therapeutic potential of tungsten oxide nanoparticles (WO 3 NPs) against DSS-induced acute colitis mice. WO 3 NPs (47.9 nm in diameter) significantly reduced intestinal inflammation, attenuated bacterial translocation, restored the colonic epithelium barriers, and remodeled gut microbiota homeostasis in inflamed colon, compared with the free tungsten (sodium tungstate). The element quantification and mapping results showed WO 3 NPs could increase the adherence of tungsten with Enterobacteriaceae in colonic mucus layer, which inhibited Enterobacteriaceae growth by microbial metabolic reprogramming and ameliorate colitis. This nano-enabled approach for tungsten reduced its deposition in the main organ except for the colon thereby improve the therapeutic efficacy with good biosafety. Together, our results provide insights into the potential nanotherapeutics of WO 3 NPs against the invasion processes of microbiota in the treatment of IBD. [Display omitted] • Reprogramming of microbial metabolism by tungsten oxide nanoparticles contributes to ameliorate IBD. • Tungsten oxide nanoparticles target intestinal microbial respiration and blunt the dysbiotic bloom of Enterobacteriaceae in acute colitis mice. • Tungsten oxide nanoparticles act as a microbe-based therapy against IBD by remodeling gut microbiota homeostasis and recovering intestinal mucosal immune barrier. [ABSTRACT FROM AUTHOR]

Abstracts A considerable amount of organic compounds could be released during coal utilization processes, and these compounds could have a significant detrimental effect on the environment and human health if freely discharged. In this study, we investigated the yields of two organic compounds (PAHs and phenols) released during the pyrolysis of coals with different ranks. And then, the formation mechanisms of PAHs and phenols are discussed by means of comparisons the correlation between release principles and coal structure. The results showed that the yields of PAHs and phenols depended to a large extent on coal structure. PAHs are formed not only by thermal breakdown of coal structure, but also by the combination of different low molecule weight compounds with each other. Monohydric phenolic carbon and aromatic ether carbon were likely to be the precursor structure of phenols. The formation of phenol, cresol and xylenol are closely related to the types of free radical (like H or CH 3 ) and the chemical structure of oxygenated aromatic carbon in coal during pyrolysis. [ABSTRACT FROM AUTHOR]

Highlights: [•] A novel application of Mo/HZSM-5 on improving BTEXN yield was investigated in situ. [•] The yield of BTEXN from coal pyrolysis was increased remarkably by HZSM-5 and Mo/HZSM-5. [•] The conditions and principle of Mo/HZSM-5 improving BTEXN yield were obtained. [ABSTRACT FROM AUTHOR]

Low chemosensitivity considerably restricts the therapeutic efficacy of gemcitabine (GEM) in pancreatic cancer treatment. Using immunohistochemical evaluation, we investigated that decreased expression of human equilibrative nucleoside transporter-1 (hENT1, which is the major GEM transporter across cell membranes) and increased expression of ribonucleotide reductase subunit 2 (RRM2, which decreases the cytotoxicity of GEM) was associated with low GEM chemosensitivity. To solve these problems, we employed a nanomedicine-based formulation of cationic liposomes for co-delivery of GEM along with siRNA targeting RRM2. Due to the specific endocytic uptake mechanism of nanocarriers and gene-silencing effect of RRM2 siRNA, this nanomedicine formulation significantly increased GEM chemosensitivity in tumor models of genetically engineered Panc1 cells with low hENT1 or high RRM2 expression. Moreover, in a series of patient-derived cancer cells, we demonstrated that the therapeutic benefits of the nanomedicine formulations were associated with the expression levels of hENT1 and RRM2. In summary, we found that the essential factors of GEM chemosensitivity were the expression levels of hENT1 and RRM2, and synthesized nanoformulations can overcome these problems. This unique design of nanomedicine not only provides a universal platform to enhance chemosensitivity but also contributes to the precision design and personalized treatment in nanomedicine. [ABSTRACT FROM AUTHOR]

Heavy metals have been reported to affect liver function. However, there is currently little and inconsistent knowledge about the effects of combined and individual urinary metals on specific parameters of liver function in the general population. Therefore, this study aimed to investigate their associations. This study involved 807 general population from the China National Human Biomonitoring of Zhejiang Province 2017–2018. Concentrations of urinary metals, including Chromium (Cr), Cobalt (Co), Nickle (Ni), Arsenic (As), Selenium (Se), Molybdenum (Mo), Cadmium (Cd), Thallium (Tl) and Lead (Pb) were measured. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein (TP), albumin (ALB), direct bilirubin (DBIL), total bilirubin (TBIL) as liver function biomarkers. Multivariable linear regression and weighted quantile sum (WQS) regression were employed to explore the associations of urinary metals with liver function biomarkers. Subgroup analysis stratified by gender and age, excluding smokers and drinkers for sensitivity analysis. Both statistical models indicated that urinary metals were positively associated with ALT and AST, while negatively with TP, ALB, DBIL and TBIL. In the WQS analysis, each quartile increase in the ln-transformed levels of metal mixtures was associated with 4.11 IU/L (95% CI: 1.07, 7.15) higher ALT and 3.00 IU/L (95% CI: 1.75, 4.25) higher AST, as well as, with 0.67 g/L (95% CI: 1.24, −0.11) lower TP, 0.74 g/L (95% CI: 1.09, −0.39) lower ALB, 0.38 μmol/L (95% CI: 0.67, −0.09) lower DBIL, and 1.56 μmol/L (95% CI: 2.22, −0.90) lower TBIL. The association between urinary metals and ALT was primarily driven by Cd (55.8%), Cr contributed the most to the association with AST (20.2%) and TBIL (45.2%), while the association with TP was primarily driven by Ni (38.2%), the association with ALB was primarily driven by As (32.8%), and the association with DBIL was primarily driven by Pb (30.9%). The associations between urinary metals and liver function might differ by sex and age. Urinary metals were significantly associated with liver function parameters. Further studies are required to clarify the relationship between heavy metals and liver function. [Display omitted] • Urinary metals were significantly associated with liver function biomarkers individually in the general population. • Both statistical models indicated that urinary metals were positively associated with ALT and AST, and negatively associated with TP, ALB, DBIL, and TBIL. • The associations between urinary metals and liver function might differ by sex and age. [ABSTRACT FROM AUTHOR]

Amifostine, an organic thiophosphate prodrug, has been clinically utilized for selective protection of normal tissues with high expression of alkaline phosphatase from oxidative damage elicited by chemotherapy or radiotherapy. However, the patients receiving amifostine suffer from severe dose-dependent adverse effects. Strategies for improvement of the protective efficacy and toxicity profile of amifostine are urgently required. Here we constructed a PEGylated amifostine (PEG-amifostine) through conjugation of amifostine to the 4-arm PEG (5000 Da) by a mild one-step reaction. The relatively large PEG-amifostine molecules clustered into spherical nanoparticles, resulting in distinct hydrolysis properties, cell uptake profile and antioxidative activity compared with the free small molecules. PEGylation prolonged the hydrolysis time of amifostine, providing sustained transformation to its functional metabolites. PEG-amifostine could be internalized into cells and translocated to acidic organelles in a time-dependent manner. The intrinsic cytotoxicity of amifostine, which is related to the reductive reactivity of its metabolites and their ability to diffuse readily, was attenuated after PEGylation. This modification impeded the interaction between free sulfhydryls and functional biomolecules, providing PEG-amifostine with an improved safety profile in vitro . Moreover, PEG-amifostine showed higher efficiency in the elimination of reactive oxygen species and prevention of cisplatin-induced cytotoxicity compared with free amifostine. Overall, our study for the first time developed a PEGylated form of amifostine which significantly improved the efficacy and decreased the adverse effects of this antioxidant in vitro with great promise for clinical translation. In vivo study is urgently needed to confirm and redeem the cytoprotective effects of the PEG-amifostine in chemotherapy. [ABSTRACT FROM AUTHOR]

Manufacturing facile and low-cost wound dressings that simultaneously meet the needs of the entire repair process remains the major challenge of effective wound healing. Herein, a series of curdlan-tannic acid hybrid hydrogels were successfully fabricated through the annealing technique. Notedly, when the mixing weigh ratio was 1:1, the hydrogel exhibited excellent physicochemical properties, including swellability, degradability, water retention, porosity, and rheology. Additionally, the hydrogel did not display significant cytotoxicity to fibroblasts and the hemolysis rate at 12 h was 3%. Interestingly, the hybrid hydrogel showed multifunctional properties, including remarkable antioxidant, antibacterial, and rapid hemostasis effects reduce blood loss by 0.35 g, that were achieved through the temperature-dependent release of tannic acid. Moreover, a full-thickness skin defect animal model was used to verify that the multifunctional hydrogel could accelerate wound healing in vivo. These results suggest that this hybrid hydrogel is a promising candidate for the clinical treatment of full-thickness wounds. [Display omitted] • A novel curdlan/tannic acid hydrogel was prepared by annealing technology. • Curdlan/tannic acid hydrogel performed adjustable physicochemical properties. • The developed hydrogel represented high safety features on mammalian cells. • The developed hydrogel showed an outstanding effect on wound healing progress. [ABSTRACT FROM AUTHOR]