Objective: To evaluate the application of Ag-Cu NPs as quorum sensing (QS) inhibitors and attenuate virulence expression to overcome the global crisis of multidrug-resistant (MDR) P. aeruginosa. Methods: Ag-Cu NPs were synthesized by co-reduction of silver-nitrate and copper-nitrate (Ag:Cu = 1:1 0.75 μM). In this cross-sectional study, a total of eighty clinical strains of P. aeruginosa were collected from patients with burns. The antibacterial and resistance pattern of the clinical isolated was determined using the microdilution and Kirby Bauer disk methods. The effect of sub-MIC of Ag-Cu NPs on the expression of lasI, exoS and toxA in five clinical isolates of imipenem-resistant P. aeruginosa was performed using qRT-PCR. Results: The characterization methods confirm the formation of the Ag-Cu alloy NPs with agglomerated spherical morphology and particle sizes of about 30-40 nm. We observed that the MIC and MBC of Ag-Cu alloy NPs against MDR P. aeruginosa was found to be 2.5 and 5 μg ml-1, respectively. The effects of a sub-inhibitory concentration of Ag-Cu NPs on MDR P. aeruginosa QS and virulence-related genes showed that the expression level of QS regulatory and virulence genes significantly decreased in both MDR P. aeruginosa and reference strain under Ag-Cu sub-MIC treatment. Conclusion: Ag-Cu NPs could be potentially used as a promising QS inhibitor and anti-virulence compound against P. aeruginosa.

The given research revealed that the size of Fe₃O₄ magnetic nanoparticles (MNPs) could be controlled by varying the pre-mixing conditions in the solvothermal method. Scanning electron microscopy (SEM) showed that the size of the MNPs gradually increased with increasing the initial temperature at which reaction components were mixed while the reaction component's mixing time was kept constant. The smallest sized MNPs were achieved among the five treatments (25, 50, 75, 100, and 125 °C) when reaction components were mixed at 25 °C, while the larger sized MNPs were synthesized among the five treatments when reaction components were mixed at 125 °C. Then, Stöber method was followed for coating silica layer onto the MNPs. However, ammonium hydroxide was replaced with potassium hydroxide as a catalyst, which significantly increased the speed of silica coating onto MNPs. The Fourier transform infrared (FTIR) spectrometer revealed that the MNPs were successfully covered with silica in five minutes. FTIR spectra exhibited a peak about 1088.8 cm-1, which belonged to the asymmetry stretching vibration of Si-O-Si. Transmission electronic microscopy (TEM) analysis was conducted to confirm the presence of silica layer onto MNPs. Thus, potassium hydroxide was successfully employed as a catalyst for quick silica layer coating onto MNPs. Furthermore, these silica coated MNPs were used to extract high quality nucleic acids from blood sample.

In this study, a rapid and highly sensitive fluorescence-linked immunosorbent assay for puerarin determination was developed by the conjugation of quantum dots with an antibody against puerarin. The linear range and detection limit of the fluorescence-linked immunosorbent assay were validated. The detection curve (y = -1041ln(x)+5366, R² = 0.999) was linear in the range of 7.8-125 ng/mL. The 50% inhibitory concentration determined by fluorescence-linked immunosorbent assay was 33.8 ng/mL puerarin in water. The limit of detection for PUE was 6.1 ng/mL. To our knowledge, this is the first report on the quantitative detection of a natural product using quantum dots as fluorescent markers. Furthermore, the newly developed fluorescence-linked immunosorbent assay was successfully applied to determine puerarin in several commercial Gegen Qinlian tablets, with a higher sensitivity than that of conventional enzyme-linked immunosorbent assays.

In this study we evaluated the impact of topical application of bioactive glass fibers loaded PRP on a deep seconddegree thermal wound and its healing process sub-streaming molecular pathway of re-epithelialization. Wistar rats were randomly divided into four groups: normal control group, model group (deep second-degree thermal wound), PRP group, and PRP+nanobioactive glass fiber group. After treatment, the changes of wounds were observed daily. H&E staining was used to evaluate the pathological changes and also, qRT-PCR was used to detect the mRNA expression of KGF, IL-1, IL-6, IL-10, TGF-β, EGF, VEGF, HIF-1α, integrin α3 and integrin β1 in wound tissues. In the current study, we observed that PRP group and the PRP group basically re-epithelized on the 21st day. The wound healing rates of the PRP+nanobioactive glass fiber group and PRP group at each time point were higher than those in the model group, while there was no significant difference in wound healing rate between the PRP+nanobioactive glass fiber group and PRP group at each time point. H&E staining showed that the pathological scores of skin wound repairing in the PRP+nanobioactive glass fiber group on the 7th, 14th and 21st day were higher than that of in the model group. The qPCR results suggested the mRNA expression of IL-1, IL-6 and IL-10 in the PRP+nanobioactive glass fiber group and the PRP group were lower than those in the untreated group on the 14th day; the expression of VEGF and EGF mRNA were higher on the 3rd day; the mRNA expression of TGF-β, HIF-1α showed a tendency of increasing first and decreasing then; integrin β1 mRNA expression increased significantly, which was highest; integrin α3 mRNA expression was higher on day 3rd and 21th, respectively. The PRP+nanobioactive glass fibers and PRP can shorten the wound healing time and improve the healing quality mainly by promoting the wound epithelization through increasing the expression of EGF, VEGF, TGF-β, HIF-1α, Integrin α3, and meanwhile increasing the release of Integrin β1 and other mechanisms.

Gingival fibroblasts play an important role in the constitution of soft tissue attachment. This study aims to investigate whether porous zirconia coating has a positive effect on promoting human gingival fibroblast attachment. The porous zirconia coating was loaded on zirconia surface by the dip coating method, surface morphology and composition were confirmed by scanning electron microscope and energy dispersive spectrometer; Tested the tensile bond strength by universal testing machine; Tested the surface roughness by roughness analyzer; Human gingival fibroblast proliferation, integrin β1 and F-actin immunofluorescence staining explored the influence of porous zirconia on the adhesion and proliferation of human gingival fibroblast. Zirconia0.2 group showed spherical zirconia particles with diameters of 3-8 μm are distributed on the surface; The bonding strength of zirconia particle coating group reached 16.1±0.1 MPa, and the surface roughness was 0.715±0.091 μm; In comparison with control group (P < 0.01), the percentage of human gingival fibroblasts adhering to zirconia was markedly higher. In zirconia group, integrin-β1 and F-actin fluoresced more obvious than in control group. Porous zirconia coating can form a porous structure on the surface and the porous structure can promote the attachment and proliferation of human gingival fibroblast, it will be more beneficial for soft tissue early sealing.

Internal implants are widely used in most orthopedic surgeries, of which titanium and its alloys are most widely used owing to the excellent corrosiveness resistance, low elastic modulus and good biocompatibility. However, implant failure still occurs for that titanium and its alloys themselves do not own antibacterial and osteogenic properties. In this work, we successfully fabricated berberine-loaded graphene oxide (GO) on the surface of biomedical titanium and systematically investigated its capabilities of antibacteria and osteogenesis. In vitro results showed that berberine had low antibacterial activity, but GO loaded with berberine on titanium (Ber&GO@Ti) exhibited superior antibacterial activity against Staphylococcus aureus (S. aureus) with the synergistic effect of GO and berberine. Meanwhile, Ber&GO@Ti performed satisfactory cytocompatibility and was capable of promoting osteogenic differentiation of MC3T3-E1 cells. In the vivo experiment, Ber&GO@Ti showed excellent antibacterial properties and inflammatory cells e.g., neutrophils had seldom been found. No visceral toxicity had been found. This multifunctional coating showed great potential in orthopedic implants.

Although the development of safe and efficient cancer therapeutic agents is essential, this process remains challenging. In this study, a mitochondria-targeted degradable nanoplatform (PDA-MnO₂-IR780) for synergistic photothermal, photodynamic, and sonodynamic tumor treatment was investigated. PDA-MnO₂-IR780 exhibits superior photothermal properties owing to the integration of polydopamine, MnO₂, and IR780. IR780, a photosensitizer and sonosensitizer, was used for photodynamic therapy and sonodynamic therapy. When PDA-MnO₂-IR780 was delivered to the tumor site, MnO₂ was decomposed by hydrogen peroxide, producing Mn2+ and oxygen. Meanwhile, alleviating tumor hypoxia promoted the production of reactive oxygen species during photodynamic therapy and sonodynamic therapy. Moreover, large amounts of reactive oxygen species could reduce the expression of heat shock proteins and increase the heat sensitivity of tumor cells, thereby improving the photothermal treatment effect. In turn, hyperthermia caused by photothermal therapy accelerated the production of reactive oxygen species in photodynamic therapy. IR780 selectively accumulation in mitochondria also promoted tumor apoptosis. In this system, the mutual promotion of photothermal therapy and photodynamic therapy/sonodynamic therapy had an enhanced therapeutic effect. Moreover, the responsive degradable characteristic of PDA-MnO₂-IR780 in the tumor microenvironment ensured excellent biological safety. These results reveal a great potential of PDA-MnO₂-IR780 for safe and highly-efficiency synergistic therapy for cancer.

The nano-hydroxyapatite/polyamide 66 (n-HA/PA66) bionic bone column, as a high-performance tissue repair and replacement material, introduced as a high osteo-induction ability agent. Nanomaterial has significantly taken a place in orthopedic surgery, however, the efficacy of using n-HA/PA66 is yet to be established. In this regard, this study evaluated various sagittal parameters (such as imaging measurement) and clinical efficacy in postoperative patients, whom underwent cervical reconstruction surgery due to cervical spondylosis myelopathy (CSM). In this study, total 62 CSM cases were enrolled between October 2016 to March 2020, and were hospitalized for cervical reconstruction surgery. 31 cases were grafted with titanium mesh and 31 cases were grafted with n-HA/P66. The sagittal parameters such as cervical spine lateral radiographs (C0-2Coob, C2-7Coob, T1S, CSVA, and TIA) were taken before operation, after operation (within 1 week), 3, 6, and 9 months after operation. In order to evaluate the clinical efficacy, we used JOA scores before, after, 3 months, 6 months and 9 months after operation. Results showed that JOA scores after the re-examination in the two groups (titanium and n-HA/P66) were significantly higher than before the operation, suggesting a well postoperative functional recovery after surgery in both groups; however, there was no significant difference in JOA score and JOA improvement index between the two groups. In regard of angles measurement (C0-2Cobb, C2-7Cobb, T1S, CSVA, and TIA), we observed no significant difference between these two groups before and after the operation. In addition, we showed that C0-2Cobb and C2-7Cobb angle had a significant positive correlation; and C0-2Cobb angle is positively correlated with T1S, and negatively correlated with CSVA. Both titanium mesh and n-HA/PA66 can be well improved and maintained within 9 months after surgery with clinical efficacy, however, using n-HA/PA66 might have more benefits.

Gold nanorods (AuNRs) have unique optical properties and biological affinity and can be used to treat tumors when conjugated with other protein molecules. Our previous studies have shown that EGFR monoclonal antibody (EGFRmAb)-modified AuNRs exert strong antitumor activity in vitro by inducing apoptosis. In this study, we tested the effects of EGFRmAb-modified AuNRs on laryngeal squamous cell cancer (LSCC) in vitro and in vivo. The in vitro results showed that EGFRmAb-modified AuNRs inhibited NP-69, BEAS-2B and Hep-2 cell growth and induced mitochondria-dependent apoptosis. The mitochondrial membrane potential was reduced, leading to the release of cytochrome C (Cyt C) and consequent activation of the intrinsic mitochondrial apoptosis pathway. Moreover, we observed that the occurrence of mitochondrial apoptosis is related to the destruction of the lysosome-mitochondria axis. To verify the effects in vivo, we also established a laryngeal tumor model in nude mice by subcutaneous transplantation. In model mice treated with EGFRmAb-modified AuNRs and irradiated with an NIR laser, tumor cell apoptosis and tumor growth were inhibited. These results suggest that EGFRmAb-modified AuNRs induced apoptosis through the intrinsic mitochondrial apoptotic pathway and are a potential candidate for cancer therapy.

The novel multifunctional electrospun textiles were fabricated by incorporating sheet-like kaolinite and silver nanoparticles (AgNps) into a polyurethane (PU) textile by using electrostatic spinning to promote wound-healing process. Threedimensional network of PU electrospun textiles offered an appropriate framework for loading kaolinite nanosheets and AgNps. Moreover, the kaolinite nanosheets healed bleeding wounds by accelerating plasma absorption, increasing blood cell concentrations, and stimulating coagulation factors. Furthermore, the AgNps killed microbes by destroying the cell membrane, while the deleterious effects were controlled by incorporation into the electrospun textile. The therapeutic effects of multifunctional electrospun textile in treating full-thickness abdominal wall defect were explored. The wound healing process could be accelerated via the textile by restoring the abdominal physiological environment, reducing the inflammatory response, and promoting collagen deposition, angiogenesis, and epithelization.

As a severe neurological disease of trauma, traumatic brain injury (TBI) leads to other disorders, such as depression, dementia and epilepsy. This study investigated whether poly d,l-(lactic-co-glycolic) acid (PLGA) PEGylated isoliquiritigenin could alleviate TBI. One hundred and eighty-three patients with clinical brain trauma were divided into two groups with or without intracranial injury in magnetic resonance imaging. The clinical results showed that serum cyclooxygenase 2 (COX-2) levels were obviously increased in the TBI patients compared to the patients with head trauma only or healthy individuals. Intracranial injection of isoliquiritigenin in TBI rats reversed TBI induced increase of COX-2 level, significantly reduced water content and contusion volume. Our findings suggest that PLGA PEG nanoparticles loaded with isoliquiritigenin can achieve the same effects as intracranial administration of isoliquiritigenin in reducing serum COX-2 level.

The aim of this study was assessing the mechanism of nanometric bone pulp activated with double gene as bone morphogenetic protein 1 (BMP-1) and vascular endothelial growth factor (VEGF) in improving the strength of centrum in osteoporosis (OP). The model of nanometric bone pulp activated with BMP-1 and VEGF double gene was established and validated. Under maximum condition of load and collapsed fragments, the model was analyzed through biomechanical test. The conditions for ALP, BGP, MLL and BMD in the model were also analyzed, and three-dimensional structural transformation was analyzed. Western blot and qRT-PCR were used to detect the effect of adding or not adding dual gene activated nano-bone stickers on OC-specific protein and mRNA; ELISA kits were used to detect the changes of RANKL pathway RANKL, OPG and TRACP5b. The maximum conformed quality and condensed intensity were strengthened with the nanometric bone pulp activated with BMP-1 and VEGF double gene. The maximum load in centrum was extremely elevated in the model, and the condition of ALP and its effect on bone was partly improved in the model. The precision and efficiency in the quality of BMD were continuously decreased. The BMD and MLF were strengthened notably in the model, and their effect on the bone was extremely improved. There was tight displayed model of trabecular in centrum and porosity was also continuously reduced. After adding the double-gene activated nano-bone stickers, the results from qRTPCR and Western blot showed that the changes of osteoclast-related genes and protein expressions were significantly down-regulated. The nanometric bone pulp activated with BMP-1 and VEGF double gene was one of ideal filled criterion. The BMD and bone strength were also elevated.

How to develop near-infrared second window (NIR-II, 1000-1700 nm) fluorescent nanoprobes with a uniform size, strong fluorescence signal and good biosafety owns great clinical requirement. Herein we reported that a two photon fluorescent nanoprobe was developed via encapsulating NIR-II-fluorescent molecules into DSPE-PEG, which was effectively endocytosized by cancer cells, and achieved strong NIR-II fluorescence imaging in cancer cells and cancer cell-beard mice models. Prepared NIR-II-fluorescent nanoprobe exhibited rapid metabolism and excellent biocompatibility. In conclusion, the prepared two photon nanoprobe owns good biosafety, and clinical translational prospect in NIR-II fluorescent imaging of tumour in vivo in near future.

Two new coordination polymers, [Cu₂(5-MeO-Hip)₄(py)₄]n (1) and [Co(5-EtO-ip)(4,4'-bipy)]n·n(MeOH) (2) (5-MeO-H₂ip is 5-methoxyisophthalic acid, 5-EtO-H₂ip is 5-ethoxyisophthalic acid, py is pyridine, and 4,4'-bipy is 4,4'-bipyridine), were created via solvothermal self-assembly. The thermal steadiness and photocatalytic functions of 1 and 2 were detected, and their application values in gastric cancer and the related mechanism were discussed. CCK-8 assay was used to determine the inhibitory activity toward gastric cancer cells' viability, and real-time RT-PCR was employed to examine the gastric cancer cells' Notch signaling pathway activity.

This study investigated the impact of magnetic mesoporous silica nanoparticles (MMSN)-encapsulated X-linked inhibitor of apoptosis protein (XIAP) and miR-233 on tumor microenvironment in cervical cancer, to provide targeted treatment and strategy, to improve radio sensitization of cancer cells. Cervical cancer cells were treated with normal saline (control group), XIAP-loaded metallic mesoporous silica nanoparticles (MMSNs), and miR-233-targeted material (XIAP group, XIAP+miR-233 group). Proliferation, apoptosis and colony forming ability of cancer cells were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method, flow cytometry and colony formation experiments. In vivo experiments were established to observe the impact of XIAP-loaded MMSNs and miR-233 on tumor growth. Administration of XIAP-loaded MMSNs suppressed tumor growth of cervical cancer, and presence of miR-233 targeted material further decreased tumor volume, increasing radio sensitization of cancer cells. In vitro experiments confirmed that, combined treatment of XIAP and miR-233 suppressed cancer cell proliferation and invasion when inducing apoptosis. XIAP MMSNs characterized by large unit surface area, high dispersion and adhesion, and prolonged circulation time, improving drug delivery and treatment selectivity of chemotherapeutic drugs. This study suggests that XIAP MMSNs with miR-233 material suppress cervical cancer cell progression and tumor growth when augmenting radiosensitization of cancer cells, providing evidence for targeted therapy for the disease.

The major histocompatibility complex (MHC) in humans is a genetic region consisting of cell surface proteins located on the short arm of chromosome 6. This is also known as the human leukocyte antigen (HLA) region. The HLA region consists of genes that exhibit complex genetic polymorphisms, and are extensively involved in immune responses. Each individual has a unique set of HLAs. Donor-recipient HLA allele matching is an important factor for organ transplantation. Therefore, an established rapid and accurate HLA typing technology is instrumental to preventing graft-verses-host disease (GVHD) in organ recipients. As of recent, high-throughput sequencing has allowed for an increase read length and higher accuracy and throughput, thus achieving complete and high-resolution full-length typing. With more advanced nanotechnology used in high-throughput sequencing, HLA typing is more widely used in third-generation single-molecule sequencing. This review article summarizes some of the most widely used sequencing typing platforms and evaluates the latest developments in HLA typing kits and their clinical applications.

Laminectomy can cause the dura mater to adhere to the surrounding scar tissue, leading to soft spinal stenosis after surgery. Although artificial laminae are considered ideal substitutes, they present challenges such as insecure fixation and insufficient bionics. In this study, we fabricated a bionic titanium alloy artificial lamina using three-dimensional (3D)-printing technology and evaluated its adhesion prevention and stability after laminectomy in pigs. An in vitro biomechanical pull-out resistance test indicated that the pull-out strength of the artificial lamina was close to that of a single pedicle screw and was significantly higher than that of a cortical screw. In vivo animal implantation results indicated precise laminectomy and artificial lamina implantation, as well as a safe operation process with the assistance of guide plates. X-ray and computed tomography results indicated the well fixation of bionic titanium alloy artificial lamina and screws 10 weeks after laminectomy. The artificial lamina was not loosened after being removed from pigs (postoperative week 12), exhibiting good stability. Additionally, no adhesion was observed in the artificial lamina group, whereas a large amount of scar tissue in the spinal canal covered the dural surface in the control group. Thus, 3D-printed bionic titanium alloy artificial lamina can prevent epidural adhesion after laminectomy, while restoring the structural stability of the posterior complex, suggesting the potential of lamina substitutes for adhesion prevention after laminectomy.

Limited chemotherapeutic efficiency, drug resistance and side effect are primary obstacles for cancer treatment. The development of co-delivery system with synergistic treatment modes should be a promising strategy. Here, we fabricated a multi-functionalized nanocarrier with a combination of chemotherapeutic agent and gold nanoparticles (AuNPs), which could integrate chemo-photothermal therapy and improve entire anti-cancer index. Particularly, Paclitaxel nanocrystals (PTX NC) were first fabricated as a platform, on surface of which AuNPs were decorated and polydopamine (PDA) layer act as capping, stabilizing and hydrophilic agents for PTX NC, providing a bridge connecting AuNPs to PTX. These AuNPs decorated PTX NC exhibited good physico-chemical properties like optimal sizes, stability and photothermal efficiency. Compared to other PTX formulations, they displayed considerably improved biocompatibility, selectivity, intracellular uptake, cytotoxicity, apoptosis induction activity and P-glycoprotein (Pgp) inhibitory capability, owing to a synergistic/ cooperative effect from AuNPs, PTX and NIR treatment, photothermal-triggered drug release and nano-scaled structure. Mitochondria-mediated signaling pathway is underlying mechanism for cytotoxic and apoptotic effect from AuNPs decorated PTX NC, in terms of Mitochondria damage, a loss of Mitochondrial membrane potential, intensified oxidative stress, DNA breakage, Caspase 3 activation, up-regulated expression in pro-apoptotic genes like p53, Caspase 3 and Bax and down-regulated level in anti-apoptotic gene like Bcl-2.

PEGylated graphene oxide nanoparticle (PEG-nGO) has been commonly used as a carrier for therapeutic drugs and vaccines, because of its unique properties, such as high solubility, more stability and increased biocompatibility in physiological solutions. This study aimed to examine the DNA damage and neurotoxicity in young mice after up to 4 h of the treatment with PEG-nGO. A single dose (5 mg/kg) of intravenous injection was administered through the tail vein of adult mice. Total genomic DNA was isolated from the control and treated animals after 1 h, 2 h, and 4 h of treatments and examined for DNA damage by diphenyl assay, DNA fragmentation Assay, and FTIR (Fourier transform infrared) techniques. DNA damage studies indicated DNA fragmentation after 1 h and 2 h of treatments followed by recovery at 4 h. FTIR analysis further supported these results and showed a detailed molecular effect of the treatments that caused single and double-strand DNA breaks at 1 to 2 h after the treatments and indicated DNA damage response and recovery at 4 h. Histopathology showed neuronal apoptosis and lesions in the brain after 1 to 2 h and invasion of inflammatory response and chromatolysis after 4 h. PEG-nGO caused immediate DNA damage and cytotoxicity to the brain and its future use as a drug carrier should be considered with caution.

With the rapid development of nanotechnology, carrier-based nano-drug delivery systems (DDSs) have been widely studied due to their advantages in optimizing pharmacokinetic and distribution profiles. However, despite those merits, some carrier-related limitations, such as low drug-loading capacity, systematic toxicity and unclear metabolism, usually prevent their further clinical transformation. Carrier-free nanomedicines with non-therapeutic excipients, are considered as an excellent paradigm to overcome these obstacles, owing to their superiority in improving both drug delivery efficacy and safety concern. In recent years, carrier-free nanomedicines have opened new horizons for cancer immunotherapy, and have already made outstanding progress. Herein, in this review, we are focusing on making an integrated and exhaustive overview of lately reports about them. Firstly, the major synthetic strategies of carrier-free nanomedicines are introduced, such as nanocrystals, prodrug-, amphiphilic drug-drug conjugates (ADDCs)-, polymer-drug conjugates-, and peptide-drug conjugates (PepDCs)-assembled nanomedicines. Afterwards, the typical applications of carrier-free nanomedicines in cancer immunotherapy are well-discussed, including cancer vaccines, cytokine therapy, enhancing T-cell checkpoint inhibition, as well as modulating tumor microenvironment (TME). After that, both the advantages and the potential challenges, as well as the future prospects of carrier-free nanomedicines in cancer immunotherapy, were discussed. And we believe that it would be of great potential practiced and reference value to the relative fields.