When antibiotic-resistant pathogenic bacteria pose a high threat to human health, bacterial multidrug efflux pumps become major contributors to the high-level antibiotic resistance in most ...microorganisms. Since traditional antibiotics are still indispensable currently, we report a dual drug delivery system to maximize the antibacterial efficacy of antibiotics by inhibiting efflux pumps in bacteria before their exposure to antibiotics. In this research, a microsphere/hydrogel composite was constructed from ciprofloxacin (Cip)-loaded poly (lactic-co-glycolic acid) (PLGA) microspheres and ginsenoside Rh2 (G-Rh2) dispersed thermo-sensitive hydrogel to treat skin infections. In vitro drug release studies indicated that while G-Rh2 in hydrogel presented a faster and short-term release manner to rapidly inhibit the NorA efflux pumps, Cip showed a sustained and long-term release behavior to provide a local high concentration gradient for facilitating drug percutaneous penetration. The combination of Cip and G-Rh2 demonstrated a high degree of synergism against both methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA), hence significantly improving their in vitro antibacterial activity and efficiency. Moreover, the antibacterial performance of the microsphere/hydrogel composite with a sequential release profile is superior to that of other formulations in mouse model of MRSA skin infections, indicating its great potential to treat antibiotic-resistant skin infections.
Instability and low transdermal permeability of protein antioxidants are major obstacles to resist oxidative stress in transdermal drug delivery system. To overcome these shortcomings, cubosomes were ...developed as an advanced transdermal delivery system to improve stability and transdermal absorption of the model antioxidant phycocyanin in this study. Glyceryl monooleate and poloxamer 407 (P407) were used to prepare cubosomes as carrier matrix and stabilizer, respectively. Phycocyanin loaded cubosomes (PC-cubosomes) were prepared by the emulsification and homogenization method. A 3 3 full factorial design was used to optimize the cubosome formulations. The final optimal PC-cubosomes possessed an average particle size of 183.2 ± 0.5 nm and a negative surface charge as well as achieved a high encapsulation efficiency of 87.2% ± 2.7%. PC-cubosomes appeared as nano-sized and well-shaped spheres with highly ordered cubical structures. The residual amount of phycocyanin in PC-cubosomes was 3-fold higher than that in the free drug solution after 10 days ultraviolet radiation exposure. In vitro release kinetics of phycocyanin from PC-cubosomes fitted to the Higuchi kinetic model, indicating that phycocyanin released from cubosomes mainly attributed to drug diffusion and dissolution. PC-cubosomes also exhibited higher permeability (39.79 μg⋅cm −2 ⋅hour −1 ) across the rat skin than phycocyanin solution (16.33 μg⋅cm −2 ⋅hour −1 ). Furthermore, PC-cubosomes were easily taken up by keratinocytes, thereby achieving a prolonged anti-oxidative stress effect. These results therefore suggested that cubosomes could be a promising transdermal delivery system to improve the stability and transdermal permeability of phycocyanin.
The emergence of multidrug resistance (MDR) is the leading cause of mortality in patients with breast cancer. Overexpressed P-glycoprotein (P-gp) that can pump out chemotherapeutics from ...multidrug-resistant cancer cells is the main cause of chemotherapy failure. P-gp inhibitors are hence increasingly used to sensitize chemotherapy to breast cancer with MDR by reducing the efflux of drugs. However, representative P-gp inhibitors usually have severe side effects and the effect of their release behavior on chemotherapy are neglected in current studies. We constructed a nano-in-thermogel delivery system with the sequential release of ginsenoside Rh2 (GRh2) and a chemotherapeutic drug in the tumor microenvironment as a drug compounding "reservoir" to combat MDR in breast cancer. Briefly, paclitaxel (PTX) and GRh2 were encapsulated in solid lipid nanoparticles (SLNs) and dispersed in a poloxamer-based thermogel (SLNs-Gel). GRh2 was used as an innovative and safe P-gp inhibitor to lower P-gp expression and cellular adenosine triphosphate context, thereby sensitizing PTX-resistant breast cancer cells (MCF-7/PTX) to PTX. Pharmacodynamic and in vivo safety studies confirmed that intratumoral injection of SLNs-Gel significantly suppressed the proliferation of PTX-resistant breast cancer and alleviated the PTX-induced hematotoxicity. The GRh2-irrigated nano-in-thermogel delivery system shows great potential in combating multidrug-resistant cancer.
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•Highly dispersed Ni/CeO2 catalysts were synthesized via hydrothermal method.•The optimum hydroliquefaction reaction condition was obtained.•Ni/CeO2 exhibited higher catalytic ...performance than CeO2 and no catalyst.•Ni/CeO2 promoted the formation of more hydrocarbons in bio-oil.•Mechanism for catalytic hydroliquefaction of rice straw over Ni/CeO2 was proposed.
A series of Ni/CeO2 catalysts were synthesized via a simple one-pot hydrothermal method and characterized by XRD, SEM, TEM, EDX, EDX mapping, Raman, H2-TPR, BET, XPS, TGA and ICP-MS. Their catalytic performances were systematically evaluated in hydroliquefaction of rice straw. The impact of reaction temperature, reaction time, H2 pressure and Ni/Ce molar ratios on product yields and distribution was also investigated. The conversion (89.08%) of rice straw and bio-oil yield (66.7%) obtained over Ni/CeO2 catalyst with a Ni/Ce molar ratio of 2/10 are superior to those over no catalyst (conversion of 73.65%, bio-oil yield of 47.96%) and pure CeO2 catalyst (conversion of 77.79%, bio-oil yield of 56.67%) under the optimum condition (290 °C, 1.0 h, and 2.0 MPa H2 pressure). GC–MS results show that the main components of bio-oil are phenols, which are high-value-added, important and useful chemicals in transportation and chemical industries. It is worth noting that the highly dispersed Ni nanoparticles and their stronger interaction between Ni and CeO2 with more oxygen vacancies facilitate high conversion of rice straw and bio-oil yield. In addition, a possible catalytic mechanism of Ni/CeO2 catalyst for hydrogenation of rice straw is accordingly proposed. This work thus offers an effective approach to improve the conversion of rice straw and bio-oil yield over Ni/CeO2 catalysts.
Severe acute respiratory syndrome-coronavirus (SARS-CoV) and SARS-like coronavirus are a potential threat to global health. However, reviews of the long-term effects of clinical treatments in SARS ...patients are lacking. Here a total of 25 recovered SARS patients were recruited 12 years after infection. Clinical questionnaire responses and examination findings indicated that the patients had experienced various diseases, including lung susceptibility to infections, tumors, cardiovascular disorders, and abnormal glucose metabolism. As compared to healthy controls, metabolomic analyses identified significant differences in the serum metabolomes of SARS survivors. The most significant metabolic disruptions were the comprehensive increase of phosphatidylinositol and lysophospha tidylinositol levels in recovered SARS patients, which coincided with the effect of methylprednisolone administration investigated further in the steroid treated non-SARS patients with severe pneumonia. These results suggested that high-dose pulses of methylprednisolone might cause long-term systemic damage associated with serum metabolic alterations. The present study provided information for an improved understanding of coronavirus-associated pathologies, which might permit further optimization of clinical treatments.
Two homologous covalent triazine frameworks (CTFs) have been developed for the first time as anode materials for high performance K-ion batteries (KIBs). The two-dimensional sheet-like structure as ...well as the regular channels in CTFs enable the process of intercalation/deintercalation of K-ions into/from the CTF interlayers reversibly. Particularly, a size effect of the porous structure is found to dominate the K-ion storage behavior. CTF-0 with a smaller pore size displays a higher K-ion storage capacity than CTF-1. Molecular simulations reveal the operation mechanism, showing that the depotassiation process in CTF-0 is exothermic while the depotassiation in CTF-1 is endothermic, which makes the deintercalation of K-ions from CTF-0 more feasible than from CTF-1 and contributes to the higher reversible capacity of CTF-0. This work provides a promising strategy for rational design of high-performance organic anode materials by structural modulation at the molecular scale.
Pore-size dominated K-ion storage behaviour in covalent triazine frameworks.
•A biomimetic brush-like polymer with a catechol structure (ADD) was designed and developed.•The Ca3(PO4)2 was deposited on soy flour and mixed with ADD to develop a biomineralized adhesive.•The dry ...and wet shear strength of resultant plywood increased by 118.8% and 750%, respectively.•The adhesive has outstanding coating performance, mildew resistance, flame retardancy.
The development of a formaldehyde-free soy flour adhesive with good coating ability, mildew resistance, and flame retardancy while maintaining high bond strength, is urgent but presents a challenge. Inspired by the strong adhesive performance derived from the brush-like structure of gecko toes, a brush-like polymer with a catechol group was synthesized to improve the adhesive behavior of soy flour adhesives. Prompted by the high strength derived from the biomineralized structure of oysters, Ca3(PO4)2 was sedimented on soy protein and combined with the brush-like polymer to construct a biomineralized structure, which endowed the resultant adhesive with mildew resistance and flame retardancy while maintaining high bond strength. The dry and wet shear strengths of the bonded plywood by the resultant adhesive increased by 118.8 % and 750 % relative to those of the unmodified adhesive. Moreover, the resultant adhesive possessed outstanding coating performance, superior mildew resistance (no mildew for 7 d), and high toughness (4.05 J of the work of adhesion). The limiting oxygen index of the resultant adhesive was increased from 26.4 % to 30.1 %. Thus, developing a system combined with a bioinspired biomineralized strategy and a brush-like polymer can potentially offer a template for the fabrication of hydrogels, functionalized surfaces, and composite materials.
Despite long being considered as "junk", transposable elements (TEs) are now accepted as catalysts of evolution. One example is Mutator-like elements (MULEs, one type of terminal inverted repeat DNA ...TEs, or TIR TEs) capturing sequences as Pack-MULEs in plants. However, their origination mechanism remains perplexing, and whether TIR TEs mediate duplication in animals is almost unexplored. Here we identify 370 Pack-TIRs in 100 animal reference genomes and one Pack-TIR (Ssk-FB4) family in fly populations. We find that single-copy Pack-TIRs are mostly generated via transposition-independent gap filling, and multicopy Pack-TIRs are likely generated by transposition after replication fork switching. We show that a proportion of Pack-TIRs are transcribed and often form chimeras with hosts. We also find that Ssk-FB4s represent a young protein family, as supported by proteomics and signatures of positive selection. Thus, TIR TEs catalyze new gene structures and new genes in animals via both transposition-independent and -dependent mechanisms.
Ischemic stroke is still the major cause of disability worldwide. Although vascular endothelial growth factor (VEGF) is able to promote both angiogenesis and functional recovery, its use is limited ...by needle-induced injury, nonhomogenous VEGF distribution, and limited VEGF retention in the brain after intracranial or intravenous injection. Here, we first present a gelatin methacryloyl (GelMA) microneedle (MN)-based platform for the sustained and controlled local delivery of an adeno-associated virus (AAV) expressing human VEGF (AAV-VEGF) that achieves homogenous distribution and high transfection efficiency in ischemic brains. An ischemic stroke model was established in adult rats, and MNs loaded with AAV-VEGF were epicortically inserted into both the ischemic core and penumbra of these rats one day after the onset of ischemia. One week later, the inflammatory response and microneedle biocompatibility were assessed by enzyme-linked immunosorbent assay (ELISA) and immunofluorescence. Eight weeks later, angiogenesis and neural stem cell proliferation and migration were assessed. GelMA MN implantation did not elicit an obvious inflammatory response and had good biocompatibility in the brain. AAV–green fluorescent protein (GFP)-loaded MNs could achieve successful transfection and homogeneous distribution in the brain cortex three weeks postoperatively. MNs loaded with AAV-VEGF increased VEGF expression and enhanced functional angiogenesis and neurogenesis. In summary, MNs might emerge as a promising platform for delivering various therapeutics to treat ischemic stroke and repair other neurologically diseased tissues.
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•Microneedle-based platform can achieve sustained and controlled drug release with homogenous distribution.•GelMA Microneedles loaded with AAV-VEGF significantly stimulate angiogenesis and maturation in infarct area.•GelMA Microneedles loaded with AAV-VEGF promote the proliferation, migration and differentiation of NSCs after stroke.•GelMA Microneedles loaded with AAV-VEGF enhance long-term neurological recovery after stroke.
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