Revelation of comprehensive cell profiling of primary and metastatic tumour ecosystems in oral squamous cell carcinoma by single-cell transcriptomic analysis.

Background: The analysis of single-cell transcriptome profiling of tumour tissue isolates helps to identify heterogeneous tumour cells, neighbouring stromal cells and immune cells. Local metastasis of lymph nodes is the most dominant and influential biological behaviors of oral squamous cell carcinoma (OSCC) in terms of treatment prognosis. Understanding metastasis initiation and progression is important for the discovery of new treatments for OSCC and prediction of clinical responses to immunotherapy. However, the identity of metastasis-initiating cells in human OSCC remains elusive, and whether metastases are hierarchically organized is unknown. Therefore, this study was conducted to understand the cellular origins and gene expression signature of OSCC at the single-cell level. Methods: Single-cell RNA sequencing (scRNA-seq) was used to analyze cells from tissue of para-carcinoma (PCA: adjacent normal tissue not less than 2 cm from the tumour), carcinoma (CA), lymph node metastasis (LNM) from patients with OSCC and PCA and CA tissue from patients with second primary OSCC (SPOSCC) after radiotherapy of nasopharyngeal carcinoma (NPC). The cell types and their underlying functions were classified. The comparisons were then conducted between the homology and heterogeneity from cell types and both conservative and heterogeneous aspects of evolution were identified. Immunohistochemistry was performed to verify the makers of cell clusters and the expression level of novel genes. Results: A single-cell transcriptomic map of OSCC was created, including 16 clusters of PCA cells, 17 clusters of CA cells, 14 clusters of left LNM cells, and 14 clusters of right LNM cells. We also discovered two novel types of cells including CD1C-CD141-dendritic cells and CD1C+_B dendritic cells. Most of the non-cancer cells are immune cells, with two distinct clusters of T lymphocytes, B lymphocytes, CD1C-CD141-dendritic cells+ and CD1C+_B dendritic cells. We also classified cells into 15 clusters for SPOSCC after radiotherapy of NPC. Determining the upregulated expression levels of IL1RN and C15orf48 as novel markers using immunohistochemistry facilitated the correct classification of OSCC including SPOSCC after radiotherapy of NPC and the prediction of their prognosis. Conclusions: The findings provided an unprecedented and valuable view of the functional states and heterogeneity of cell populations in LNM of OSCC and SPOSCC after radiotherapy of NPC at single-cell genomic resolution. Moreover, this transcriptomic map discovered new cell types in mouth, and novel tumour cell-specific markers/oncogene.

Microbial communities in crude oil phase and filter-graded aqueous phase from a Daqing oilfield after polymer flooding.

AIMS: The aim was to characterize indigenous micro-organisms in oil reservoirs after polymer flooding (RAPF). METHODS: The microbial communities in the crude oil phase (Oil) and in the filter-graded aqueous phases Aqu0.22 (>0.22 µm) and Aqu0.1 (0.1-0.22 µm) were investigated by 16S rRNA gene high-throughput sequencing. RESULTS: Indigenous micro-organisms related to hydrocarbon degradation prevailed in the three phases of each well. However, obvious differences in bacterial compositions were observed amongst the three phases of the same well and amongst the same phase of different wells. The crude oil and Aqu0.22 shared many dominant bacteria. Aqu0.1 contained a unique bacterial community in each well. Most bacteria in Aqu0.1 were affiliated to culturable genera, suggesting that they may adapt to the oil reservoir environment by reduction of cell size. Contrary to the bacterial genera, archaeal genera were similar in the three phases but varied in relative abundances. The observed microbial differences may be driven by specific environmental factors in each oil well. CONCLUSIONS: The results suggest an application potential of microbial enhanced oil recovery (MEOR) technology in RAPF. The crude oil and Aqu0.1 contain many different functional micro-organisms related to hydrocarbon degradation. Both should not be overlooked when investing and exploring the indigenous micro-organisms for MEOR. SIGNIFICANCE AND IMPACT OF THE STUDY: This work facilitates the understanding of microbial community structures in RAPF and provides information for microbial control in oil fields.

Comparison between direct use and PLGA nanocapsules containing drug of traditional Chinese medicine, Tiaojing Zhixue, in treatment of dysfunctional uterine bleeding.

Dysfunctional uterine bleeding is menstrual bleeding in abnormal volume, duration, or time, and it is a common problem in women. A wide range of drug therapies, with varying efficacy, is available for women with dysfunctional uterine bleeding. The use of herbal and traditional medicine is one of the ways to treat this disease, which has fewer side effects than chemical drugs. On the other hand, these medicines have less effect on treatment than chemical drugs. Therefore, increasing their effectiveness in the treatment of diseases has always been important. For this purpose, in this study, a comparison was done between direct use and PLGA nanocapsules containing Tiaojing Zhixue, in the treatment of dysfunctional uterine bleeding. First, PLGA nanocapsules containing Tiaojing Zhixue were synthesized by the electrospray technique. Then 80 women with dysfunctional uterine bleeding were treated with this medicine. These people were divided into two groups of 40 people. The first group was treated with 20mg of Tiaojing Zhixue and the other group was treated with PLGA nanocapsules containing Tiaojing Zhixue for eight months. The duration and frequency of bleeding from one month before the start of treatment and during the eight months after the start of treatment (second, fourth, and eighth month) were assessed in two groups. The two groups were homogeneous in terms of mean frequency of bleeding and mean duration of bleeding before starting treatment. The positive response in the PLGA nanocapsules treatment group (75%) was higher than the direct use drug treatment group (42.5%) (P < 0.01). The rate of side effects was the same in each group. Due to the effectiveness of PLGA nanocapsules in the treatment of dysfunctional uterine bleeding and the lack of side effects, it can be considered as an alternative medicine for the treatment of this disorder.

Photoluminescent coral-like carbon-branched polymers as nanoprobe for fluorometric determination of captopril.

The authors describe the synthesis of fluorescent coral-like carbon nano-branched polymers (PCNBPs) co-doped with nitrogen and phosphorus. Uric acid and phosphoric acid act as nitrogen and phosphorus sources, respectively. The PCNBPs have a coral-like branched structure, are cross-connected, and < 20 nm in skeleton diameter. Their blue fluorescence, best measured at excitation/emission wavelengths of 330/425 nm, is quenched by mercury (II) ions due to the specifically restricted rigid conformation caused by the interaction of phosphorus, nitrogen, and oxygen groups on the surface of the PCNBPs. Fluorescence is selectivity quenched by Hg(II) but restored in addition of the hypertension drug captopril (CAP) in the range 50 nM to 40 µM concentration range. Fluorescence recovery is attributed to the effectively specific interactions between the thiol group of CAP and Hg(II). The method was applied to the determination of the concentration of Cap in pharmaceutical samples, and recoveries were between 97.6 and 105.1%. Graphical abstract Fluorescent coral-like carbon nano-branched polymers (PCNBPs) co-doped with nitrogen and phosphorus are described. Their fluorescence is selectivity quenched by Hg(II) but restored in addition of the hypertension drug captopril (Cap) in the range 50 nM to 40 µM concentration range.

Mineralogical characterisation and magnetic separation of vanadium-bearing converter slag.

The recycling of metallic iron is commonly the first step to fully use the converter slag, which is the biggest waste discharge in the steelmaking process. This study presents a proposed improved process of separating metallic iron from vanadium-bearing converter slag more efficiently. The mineralogical and morphological characteristics of the converter slag were first investigated, and the results showed that most of the iron was incorporated in the spinel and olivine. Grinding, sieving and magnetic separation were combined to recover metallic iron from the converter slag, and yielded approximately 41.5% of iron in which the iron content was as high as 85%, and the non-magnetic concentrate contains 8.56% vanadium with a yield of 95.3% and 8.63% titanium with a yield of 85.3%. The magnetic part can be used as the raw materials in the steel making process, whereas the non-magnetic part can be used as the raw materials for the further extraction of vanadium.

Preparation of intravenous injection nanoformulation via co-assemble between cholesterylated gemcitabine and cholesterylated mPEG: enhanced cellular uptake and intracellular drug controlled release.

The objective of this study was to prepare the CHS-mPEG/CHS-dFdC nanoformulation could be administrated through intravenous injection in nude mice. Particularly, CHS-mPEG was selected to co-assemble with CHS-dFdC to improve the prodrug concentration and enhance the stability of nanoformulation. The nanoformulation could be prepared by codissolution-coprecipitation. All of the nanoformulations kept stable in PBS at 4 °C or simulative human plasma at 37 °C. As molar ratios of CHS-mPEG1900/CHS-dFdC increased from 0.1/1 to 2/1, the weight concentration of CHS-dFdC increased from 2.5 to 15 mg/mL. It was found the optimal CHS-mPEG1900/CHS-dFdC nanoformulation displayed controlled drug release in simulative lysosome condition. The amount of released dFdC reached up to 90% within 10 h. It also exhibited enhanced cellular uptake ability, 7-folds higher than that of dFdC during 2.5 h incubation. And it showed superior cytotoxicity resulted from the enhanced cellular uptake ability on BxPC-3 cells.

Enhanced Antiglioblastoma Efficacy of Neovasculature and Glioma Cells Dual Targeted Nanoparticles.

Combining treatment of anticancer cells and antiangiogenesis is considered to be a potential targeted strategy for brain glioblastoma therapy. In this study, by utilizing the overexpression of Interleukin 13 receptor α2 (IL-13Rα2) on the glioma cells and heparan sulfate on neovascular endothelial cells, we developed a paclitaxel (PTX) loaded Pep-1 and CGKRK peptide-modified PEG-PLGA nanoparticle (PC-NP-PTX) for glioma cells and neovasculature dual-targeted chemotherapy to enhance the antiglioma efficacy. There were significant differences both on the enhancement of cellular uptake in HUVEC and C6 cells and on the improvement of in vitro antiglioma activity in the respect of proliferation, tumor spheroid growth, tube formation, and migration between PC-NP-PTX and Taxol and NP-PTX. As for C6 cells, the IC50 were 3.59 ± 0.056, 2.37 ± 0.044, 1.38 ± 0.028, 1.82 ± 0.035, and 1.00 ± 0.016 µg/mL of Taxol, NP-PTX, Pep-NP-PTX, CGKRK-NP-PTX, and PC-NP-PTX, and for HUVEC cells, the IC50 were 0.44 ± 0.006, 0.33 ± 0.005, 0.25 ± 0.005, 0.19 ± 0.004, and 0.16 ± 0.004 µg/mL of Taxol, NP-PTX, Pep-NP-PTX, CGKRK-NP-PTX, and PC-NP-PTX, respectively. In vivo distribution assays confirmed that PC-NP-PTX targeted and accumulated effectively at glioma site. PC-NP-PTX showed a longer median survival time of 61 days when compared with Taxol (22 days), NP-PTX (24 days), Pep-NP-PTX (32 days), and CGKRK-NP-PTX (34 days). The in vivo antiglioma efficacy and safety evaluation showed PC-NP-PTX significantly enhanced the antiglioma efficacy and displayed negligible acute toxicity.

Application of Local Injection of Botulinum Toxin A in Cosmetic Patients with Congenital Drooping Mouth Corner.

OBJECTIVE: This study aimed to investigate the clinical application and efficacy of local injection of botulinum toxin A (BTX-A) at the depressor anguli oris in patients with congenital drooping mouth corner. METHODS: From September 2013 to March 2015, 36 cosmetic patients received local injections of botulinum toxin A at the depressor anguli oris, with 1-3 injection sites in the moving region of the depressor anguli oris on each side. At each injection site, 2-4 U of BTX-A was injected, and the total dose for any unilateral treatment did not exceed 8 U. The change in the degree of drooping of the mouth corner before and after the injection was analyzed using statistical methods. The clinical efficacy, preservation time, and adverse reactions were observed. RESULTS: The degree of drooping of the mouth corners of the cosmetic patients before the treatment was compared with that at 1 month after using a paired t test, and the difference was statistically significant, with P < 0.01. The treatment results were satisfactory, and the effect was preserved for 6-9 months. None of the 36 cosmetic patients had any complications of bruising, infection, dysfunction in opening and closing the mouth, smile asymmetry, drooling, or dysarthria after the injection. CONCLUSIONS: The local injection of BTX-A at the depressor anguli oris can effectively lift a drooping mouth corner, thereby improving the depressed, stern, and aged appearance of the face. The performance of this treatment is simple, safe, and easy to perform in clinical applications. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Infratemporal Fossa Metastasis of Non-Small-Cell Lung Adenocarcinoma: A Case Report and Literature Review.

Neoplasms in the infratemporal fossa (ITF) are rare and insidious lesions that cause various symptoms due to involvement of the temporomandibular joint (TMJ), paranasal sinuses, and orbit. Here, we report a case of metastatic non-small cell lung adenocarcinoma in the ITF. The patient presented with facial pain and limited mouth opening, which did not respond to treatment for TMJ disorder, and a neoplasm was discovered in the ITF through medical imaging. With an open biopsy, the diagnosis was finalized. This report suggested that the physician should consider lesions in the ITF when facial pain and limited mouth opening failed local treatment, and distant metastasis of malignant tumor should be alerted. We also reviewed the literature regarding metastatic cancer to the ITF.

Novel poly(lactic-co-glycolic acid) nanoliposome-encapsulated diclofenac sodium and celecoxib enable long-lasting synergistic treatment of osteoarthritis.

BACKGROUND: Diclofenac sodium (DS) and celecoxib (CEL) are primary anti-inflammatory agents used in the treatment of osteoarthritis (OA). Formulating these drugs into extended-release versions can effectively address the issue of multiple daily doses. In this study, we designed and synthesized a novel poly(lactic-co-glycolic acid) (PLGA) nanoliposome as a dual-drug delivery sustained-release formulation (PPLs-DS-CEL) to achieve long-lasting synergistic treatment of OA with both DS and CEL. METHODS: PPLs-DS-CEL was synthesized by the reverse evaporation method and evaluated for its physicochemical properties, encapsulation efficiency, drug release kinetics and biological properties. A rat OA model was established to assess the therapeutic efficacy and biosafety of PPLs-DS-CEL. RESULTS: The particle size of PPLs-DS-CEL was 218.36 ± 6.27 nm, with a potential of 32.56 ± 3.28 mv, indicating a homogeneous vesicle size. The encapsulation of DS and CEL by PPLs-DS-CEL was 95.18 ± 4.43% and 93.63 ± 5.11%, with drug loading of 9.56 ± 0.32% and 9.68 ± 0.34%, respectively. PPLs-DS-CEL exhibited low cytotoxicity and hemolysis, and was able to achieve long-lasting synergistic analgesic and anti-inflammatory therapeutic effects in OA through slow release of DS and CEL, demonstrating good biosafety properties. CONCLUSION: This study developed a novel sustained-release nanoliposomes formulation capable of co-loading two drugs for the long-acting synergistic treatment of OA. It offers a new and effective therapeutic strategy for OA treatment in the clinic settings and presents a promising approach for drug delivery systems.

Oral Microbiota and Porphyromonas gingivalis Kgp Genotypes Altered in Parkinson's Disease with Mild Cognitive Impairment.

Cognitive impairment (CI) is a common complication of the non-motor symptoms in Parkinson's disease (PD), including PD with mild cognitive impairment (PD-MCI) and PD dementia. Recent studies reported the oral dysbiosis in PD and CI, respectively. Porphyromonas gingivalis (P. gingivalis), a pathogen of oral dysbiosis, plays an important role in PD, whose lysine-gingipain (Kgp) could lead to AD-type pathologies. No previous study investigated the composition of oral microbiota and role of P. gingivalis in PD-MCI. This study aimed to investigate the differences of oral microbiota composition, P. gingivalis copy number, and Kgp genotypes among PD-MCI, PD with normal cognition (PD-NC) and periodontal status-matched control (PC) groups. The oral bacteria composition, the copy number of P. gingivalis, and the Kgp genotypes in gingival crevicular fluid from PD-MCI, PD-NC, and PC were analyzed using 16S ribosomal RNA sequencing, quantitative real-time PCR, and MseI restriction. We found that the structures of oral microbiota in PD-MCI group were significantly different compared to that in PD-NC and PC group. The relative abundances of Prevotella, Lactobacillus, Megasphaera, Atopobium, and Howardella were negatively correlated with cognitive score. Moreover, there was a significant difference of Kgp genotypes among the three groups. The predominant Kgp genotypes of P. gingivalis in the PD-MCI group were primarily Kgp II, whereas in the PD-NC group, it was mainly Kgp I. The Kgp II correlated with lower MMSE and MoCA scores, which suggested that Kgp genotypes II is related to cognitive impairment in PD.

Cellulose-ethylenediaminetetraacetic acid conjugates protect mammalian cells from bacterial cells.

Cellulose-ethylenediaminetetraacetic acid (EDTA) conjugates were synthesized by the esterification of cellulose with ethylenediaminetetraacetic dianhydride (EDTAD). The new materials provided potent antimicrobial activities against Staphylococcus aureus (S. aureus, Gram-positive bacteria) and Pseudomonas aeruginosa (P. aeruginosa, Gram-negative bacteria), and inhibited the formation of bacterial biofilms. The biocompatibility of the new cellulose-EDTA conjugates was evaluated with mouse skin fibroblasts for up to 14 days. SEM observation and DNA content analysis suggested that the new materials sustained the viability of fibroblast cells. Moreover, in mouse skin fibroblast-bacteria co-culture systems, the new cellulose-EDTA conjugates prevented bacterial biofilm formation and protected the mammalian cells from the bacterial cells for at least one day.

3D-fEA of stress levels and distributions for different bases under a Class I composite restoration.

PURPOSE: To investigate the level and distribution of stresses in composite-restored mandibular first molars with various combinations of base materials. METHODS: The finite element package Abaqus was used for the stress analysis. Several different base materials were evaluated [light-cured glass ionomer (LC-GI), chemically-cured calcium hydroxide (CC-CH), and light-cured calcium hydroxide (LC-CH)] in combination with light-cured composite (LC-CP). Four models of restored molars with Class I deep cavity preparations were simulated, including (1) LC-GI/LC-CP, (2) CC-CH/LC-CP, (3) CC-CH/LC-GI/LC-CP, and (4) LC-CH/LC-GI/LC-CP. A 250N static single-point load was applied vertically on the central fossa of the tooth to simulate physical loading conditions. RESULTS: In each case, the peak stresses were found to be concentrated mainly at the interfaces between the various materials and the dental tissues. In the residual tooth structures, the maximum Von Mises stresses were 20.01 MPa in model LC-GI/LC-CP, 23.85 MPa in model CC-CH/LC-CP, 23 MPa in model CC-CH/LC-GILC-CP and 21.83 MPa in model LC-CH/LC-GIILC-CP. In the LC-CP restorations, the maximum Von Mises stresses were 43.68 MPa in model LC-GILC-CP, 42.24 MPa in model CC-CH/LC-CP, 42.29 MPa in model CC-CH/LC-G/LC-CP and 42.55 MPa in model LC-CH/LC-GI/LC-CP. In the bases, the maximum Von Mises stresses were 5.71 MPa in model LC-GI/LC-CP, 0.85 MPa in model CC-CH/LC-CP, 4.69 MPa in model CC-CH/LC-GI/LC-CP, and 4.93 MPa in model LC-CH/LC-GILC-CP.

Tumor-Associated Neutrophil Extracellular Traps Regulating Nanocarrier-Enhanced Inhibition of Malignant Tumor Growth and Distant Metastasis.

Tumor-associated neutrophil extracellular traps (NETs) play a critical role in promoting tumor growth and assisting tumor metastasis. Herein, a smart nanocarrier (designated as mP-NPs-DNase/PTX) based on regulating tumor-associated NETs has been developed, which consists of a paclitaxel (PTX) prodrug nanoparticle core and a poly-l-lysine (PLL) conjugated with the matrix metalloproteinase 9 (MMP-9)-cleavable Tat-peptide-coupled deoxyribonuclease I (DNase I) shell. After accumulating at the site of the tumor tissue, the nanocarrier can release DNase I in response to MMP-9 to degrade the structure of NETs. Then, the remaining moiety can uptake the tumor cells via the mediation of exposed cell penetrating peptide, and the PTX prodrug nanoparticles will lyse in response to the high intracellular concentration of reduced glutathione to release PTX to exert a cytotoxic effect of tumor cells. Through in vitro and in vivo evaluations, it has been proven that mP-NPs-DNase/PTX could serve as potential NET-regulated nanocarrier for enhanced inhibition of malignant tumor growth and distant metastasis.

Clinical Characteristics and Surgical Outcomes of Sinonasal Lesions Associated With Tumor-Induced Osteomalacia.

OBJECTIVE: To investigate the clinical characteristics and surgical outcomes of sinonasal tumors associated with tumor-induced osteomalacia (TIO). STUDY DESIGN: Retrospective case series. SETTING: Single tertiary center. METHODS: We studied the clinical characteristics and surgical outcomes of 43 patients (22 male, 21 female) who had lesions in the nasal cavity and paranasal sinus associated with TIO and underwent surgery between August 2006 and November 2019. RESULTS: The mean ± SD duration between the onset of symptoms and surgery was 3.9 ± 2.6 years. The most common tumor site was the ethmoid sinus (76.7%), and the skull base was involved in 12 cases. Phosphaturic mesenchymal tumors were diagnosed in 41 patients, among whom there was 1 multifocal case. Another 2 cases involved odontogenic fibroma and hemangiofibroma, respectively. Serum phosphorus normalized in 39 cases within 4.4 ± 2.3 days, and serum fibroblastic growth factor 23 normalized within 1 day; clinical symptoms, however, gradually improved within several months after the first operation. There was no significant difference in the recovery rate between endoscopic and open surgery (P = 0.639). Two patients with recurrent cases and 2 with nonremission cases recovered after a sinonasal reoperation. The patient with a multifocal case recovered after the resection of the tumors in the ethmoid sinus and mandible. The overall recovery rate was 97.7%. CONCLUSION: Most sinonasal tumors associated with TIO are located in the ethmoid sinus, and the skull base is involved in some cases. Complete excision of the tumor leads to recovery, and endoscopic surgery could achieve recovery rates similar to those of open surgery.

Early Discrimination Between Tumor-Induced Rickets/Osteomalacia and X-Linked Hypophosphatemia in Chinese Children and Adolescents: A Retrospective Case-Control Study.

In children and adolescents, distinguishing tumor-induced rickets/osteomalacia (TIR/O) from hereditary hypophosphatemic rickets/osteomalacia (HR/O) is a medical challenge. We retrospectively studied 10 Chinese children and adolescents with TIR/O who underwent surgery at a mean age of 17.4 ± 2.1 years and compared their characteristics to 24 age- and sex-matched patients with X-linked hypophosphatemia (XLH). Positive family history of HR/O and dental problems, such as enamel hypoplasia and dental abscess, were reported in 8 (33.3%) and 5 (20.8%) patients with XLX, respectively, but not in patients with TIR/O. In addition, in comparison with XLH patients, TIR/O patients had an older disease onset age (150 versus 24 months, p < 0.001), a higher height standard deviation score (SDS; -1.2 ± 1.8 versus -4.0 ± 1.4, p < 0.001), a lower Z-score of bone mineral density (BMD) at lumbar spine (LS) (-3.9 [6.0] versus +1.8 [7.0], p < 0.001), and a higher serum intact fibroblast growth factor 23 (FGF23) level (500.27 ± 87.20 versus 121.71 ± 70.94 pg/mL, p < 0.001), corresponding to a lower serum phosphate level (0.52 ± 0.07 versus 0.64 ± 0.11 mmol/L, p = 0.005) and a higher serum alkaline phosphatase (ALP) level (557 [631] versus 305 [249] U/L, p = 0.005). We generated receiver operating characteristic (ROC) curves and calculated the area under the ROC curve (AUC). The AUCs of onset age, FGF23, and LS Z-score were equal to 1, suggesting that these are excellent indices for the differential diagnosis between TIR/O and XLH. In summary, our study furthers our understanding of the spectrum of clinical, biochemical, and pathologic findings associated with TIR/O. For children and adolescent patients with HR/O, a comprehensive and careful clinical and laboratory evaluation is of great importance, and we recommend enquiry of the family history, onset age, and dental problems, as well as measurement of serum FGF23 and BMD. © 2021 American Society for Bone and Mineral Research (ASBMR).

Ultrathin carbon nanotube-DNA hybrid membrane formation by simple physical adsorption onto a thin alumina substrate.

Ultrathin carbon nanotube membranes can be prepared on alumina substrates by a facile immersion-adsorption approach, which involves two steps, the first step DNA wrapping and the second step uniform adsorption of the DNA-wrapped nanotubes onto porous alumina. In this approach, DNA wrapping imparts a hydrophilic nature to the carbon nanotubes, which enhances the interaction between the nanotubes and hydrophilic porous alumina and results in the self-assembly formation of ultrathin nanotube membranes with well-controlled thickness, biocompatibility, conductivity and optical properties.

A new strategy for accurate targeted diagnosis and treatment of cutaneous malignant melanoma: dual-mode phase-change lipid nanodroplets as ultrasound contrast agents.

BACKGROUND: Currently, effective detection and treatment of cutaneous malignant melanoma (CMM) still face severe challenges. Ultrasound molecular imaging as a noninvasive and easy-to-operate method is expected to bring improvements for tumor detection. PURPOSE: The aim of this research is to prepare novel phase-change ultrasound contrast agents, Nds-IR780, which can perform not only dual-mode molecule-targeted imaging but also targeted photothermal therapy for CMM. METHODS: A double emulsion process was used to prepare the Nds-IR780. Then, the entrapment rate and drug loading of IR-780 iodide in Nds-IR780 were detected by high-performance liquid chromatography. The biocompatibility of Nds-IR780 was evaluated by a CCK-8 assay and the characteristics and stability of that were verified through the particle size analyzer, laser scanning confocal microscopy (LSCM) and transmission electron microscopy (TEM). The abilities of dual-mode molecule-targeted imaging and targeted photothermal therapy for Nds-IR780 were confirmed via the in vitro and in vivo experiments. RESULTS: Nds-IR780 had good size distribution, polydispersity index, stability and biosafety. The in vitro and in vivo experiments confirmed that Nds-IR780 were capable of targeting CMM cells with high affinity (22.4±3.2%) and facilitating dual-mode imaging to detect the primary lesion and sentinel lymph nodes (SLNs) of CMM. Furthermore, the photothermal ablation of CMM mediated by Nds-IR780 was very effective in vivo. CONCLUSION: The newly prepared Nds-IR780 were observed to be effective targeted theranostic probe for the precise detection and targeted treatment of CMM.

Bioengineered Boronic Ester Modified Dextran Polymer Nanoparticles as Reactive Oxygen Species Responsive Nanocarrier for Ischemic Stroke Treatment.

Ischemic stroke is a leading cause of long-term disability and death worldwide. Current drug delivery vehicles for the treatment of ischemic stroke are less than satisfactory, in large part due to their short circulation lives, lack of specific targeting to the ischemic site, and poor controllability of drug release. In light of the upregulation of reactive oxygen species (ROS) in the ischemic neuron, we herein developed a bioengineered ROS-responsive nanocarrier for stroke-specific delivery of a neuroprotective agent, NR2B9C, against ischemic brain damage. The nanocarrier is composed of a dextran polymer core modified with ROS-responsive boronic ester and a red blood cell (RBC) membrane shell with stroke homing peptide (SHp) inserted. These targeted "core-shell" nanoparticles (designated as SHp-RBC-NP) could thus have controlled release of NR2B9C triggered by high intracellular ROS in ischemic neurons after homing to ischemic brain tissues. The potential of the SHp-RBC-NP for ischemic stroke therapy was systematically evaluated in vitro and in rat models of middle cerebral artery occlusion (MCAO). In vitro results showed that the SHp-RBC-NP had great protective effects on glutamate-induced cytotoxicity in PC-12 cells. In vivo pharmacokinetic (PK) and pharmacodynamic (PD) testing further demonstrated that the bioengineered nanoparticles can drastically prolong the systemic circulation of NR2B9C, enhance the active targeting of the ischemic area in the MCAO rats, and reduce ischemic brain damage.

Microhoneycomb Monoliths Prepared by the Unidirectional Freeze-drying of Cellulose Nanofiber Based Sols: Method and Extensions.

Monolithic honeycomb structures have been attractive to multidisciplinary fields due to their high strength-to-weight ratio. Particularly, microhoneycomb monoliths (MHMs) with micrometer-scale channels are expected as efficient platforms for reactions and separations because of their large surface areas. Up to now, MHMs have been prepared by a unidirectional freeze-drying (UDF) method only from very limited precursors. Herein, we report a protocol from which a series of MHMs consisting of different components can be obtained. Recently, we found that cellulose nanofibers function as a distinct structure-directing agent towards the formation of MHMs through the UDF process. By mixing the cellulose nanofibers with water soluble substances which do not yield MHMs, a variety of composite MHMs can be prepared. This significantly enriches the chemical constitution of MHMs towards versatile applications.