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Objective The loss of neural ability leading to subsequent diminishing of motor function and the impairment below the location of the injury is a result of the SCI (Spinal Cord Injury). Among the many therapeutic agents for SCI, the exosomes considered as extracellular vesicles seem to be the most promising. Sonic Hedgehog (Shh) is an exosome-carrying protein. This Study's purpose was to identify whether Shh is required for exosomes from BMSCs (mesenchymal stem cells of the bone) and plays a protective effect on SCI. Methods Spinal cord injection with shRNA Shh-adeno associated virus (sh-Shh-AAV) were used to silence Shh. Exosomes were extracted from BMSCs. Rats that had suffered SCI were given intravenous injections of exosomes through the veins of the tail. Immunohistochemistry was used to identify the expression of Shh glycoprotein molecule as well as the expression of Gli-1 (glioma-associated oncogene homolog 1) in the rat spinal cord tissues. Western blot was performed to measure the levels of growth associated protein-43 (GAP-43). The BBB (Basso Beattie Bresnahan) score was used to assess the motor functions of the hind legs. In the same manner, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling or TUNEL and Nissl Staining was deployed to assess the level of regeneration of neurons and assess the level of histopathological damage in the tissues of the Spinal Cord. Results In the case of the rats with SCI, the levels of display of Gli-1 and Shh showed dramatic improvement after the BMSCs exosome injections. In comparison to rats with SCI, the subjects of BMSCs exosomes group showed an improvement in their SCI, including a higher BBB score and Nissl body count, increasing GAP-43 expression, along with a much-decreased number of cells that suffered apoptosis. While the exosome effect on Spinal Cord Injury was completely ineffective in rats that had Shh silencing. Conclusions Exosomes secreted from BMSCs showed great effectiveness in the SCI healing with a vital involvement of Shh in this repair.

Diaporisoindole B (DPB), an isoprenylisoindole alkaloid isolated from the mangrove endophytic fungus

This study used litchi (Heiye) wine and distilled spirit as raw experimental materials to analyze the volatile aroma compounds. Qualitative and quantitative determination of aromatic components was studied using stir bar sportive extraction (SBSE) and gas chromatography coupled to mass spectrometry (GC/MS). Results indicated that a total of 128 different types of aroma compounds were observed, which belonged to six chemical groups, including 39 esters, 16 alcohols, 16 acids, 22 terpenes, 17 aldehydes and ketones, and 18 other compounds. In particular, esters were the highest among all six categories and represented approximately 52% of the total flavor component content in litchi distilled spirit. The odor activity values (OAVs) revealed 22 types of aroma compounds with OAVs >1 in this test. It is possible that the produced litchi distilled spirit had a stronger varietal character due to the increased concentrations and OAVs of β‐damascenone, linalool, ethyl butyrate, ethyl isovalerate, ethyl caproate, trans‐rose oxide, and cis‐rose oxide. Taking the OAVs into account, we evaluated the characteristic aromas for litchi wine and litchi distilled spirit., It is possible that the produced litchi distilled spirit had a stronger varietal character due to the increased concentrations and OAVs of β‐damascenone, linalool, ethyl isovalerate, ethyl butyrate, ethyl caproate, trans‐rose oxide, and cis‐rose oxide since these compounds are known to play a decisive fruit and flower aroma in the distilled spirit.

Background Spinal cord injuries (SCIs) can cause a loss of neurons and associated sensory and motor functionality below the injured site. No approaches to treating SCIs in humans have been developed to date. Exosomes are extracellular vesicles that hold promise as a potential therapeutic modality when treating such injuries. The present study was thus designed to determine whether sonic hedgehog (Shh)-overexpressing bone mesenchymal stem cell (BMSC)-derived exosomes were protective in the context of SCIs. Methods Exosomes were extracted from control or Shh lentivirus-transduced BMSCs, yielding respective BMSC-Exo and BMSC-Shh-Exo preparations which were intravenously injected into SCI model rats. Shh expression in spinal cord tissues in these animals was then assessed via immunohistochemical staining, while Basso-Beattie-Bresnahan (BBB) scores were utilized to measure high limb motor function. Neuronal damage and regeneration within the spinal cord were additionally evaluated via terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), Nissl, hematoxylin and eosin, and immunofluorescent staining. Results Both BMSC-Exo and BMSC-Shh-Exo preparations significantly increased Shh expression in the spinal cord of SCI model rats and improved BBB scores in these treated animals, while also increasing the frequencies of Nissl- and NeuN-positive neurons are reducing the numbers of apoptotic and GFAP-positive neurons. While both treatments yielded some degree of benefit to treated animals relative to untreated controls, BMSC-Shh-Exos were more beneficial than were control BMSC-Exos. Conclusions Shh-overexpressing BMSC-derived exosomes represent an effective treatment that can facilitate SCI repair in rats.

Multidrug-resistance (MDR) featuring complicated and poorly defined mechanisms is a major obstacle to the success of cancer chemotherapy in the clinic. Compound nanoparticles comprising multiple cytostatics with different mechanisms of action are commonly developed to tackle the multifaceted nature of clinical MDR. However, the different pharmacokinetics and release profiles of various drugs result in inconsistent drug internalization and suboptimal drug synergy at the tumor sites. In the present study, a type of self-targeting hyaluronate (HA) nanogels (CDDPHANG/DOX) to reverse drug resistance through the synchronized pharmacokinetics, intratumoral distribution, and intracellular release of topoisomerase II inhibitor doxorubicin (DOX) and DNA-crosslinking agent cisplatin (CDDP) is developed. With prolonged circulation time and enhanced intratumoral accumulation in vivo, CDDPHANG/DOX shows efficient drug delivery into the drug-resistant MCF-7/ADR breast cancer cells and enhanced antitumor activity. Besides, fluorescence imaging of DOX combined with the micro-computed tomography (micro-CT) imaging of CDDP facilitates the visualization of this combination tumor chemotherapy. With visualizable synchronized drug delivery, the self-targeting in situ crosslinked nanoplatform may hold good potential in future clinical therapy of advanced cancers.

The species of Camellia nitidissima Chi (CC) and C. euphlebia Merr. ex Sealy (CE) are two most important plant sources for commercialized herbal tea (Jinhuacha) worldwide. However, some other species of camellia genus are also sold as alternatives in market due to the great commercial value. In this study, the similarity and difference of CC and CE as well as C.insularis (CI) are comprehensively compared both in chemistry and pharmacology. Based on the ultraperformance liquid chromatography coupled with a hybrid quadrupole orthogonal time-of-flight mass spectrometer(UPLC-QTOF-MS) analysis, a sequential-optimization based new statistical model has been developed by combining the untargeted metabolomics and fingerprint analyses, and successfully applied for chemical pattern recognition and discrimination of three yellow camellias species. The results indicated that CC, CE and CI could be well discriminated with the optimized chemical combination including quercetin-3-O-rhamnoside (C2), okicamelliaside (C4), Kaempferol 7-O-rhamnoside (C6), Corymboside (C9), asiatic acid-glc-rha-xyl (C11) and 3'-methy-4'-glucoside-ellagic acid (C14). Moreover, the 30 % ethanolic extracts of yellow camellias species presented the optimal activities on anti-inflammation/anti-oxidation in LPS-stimulated Raw264.7 macrophages dose-dependently. The averaged 50 % inhibitory concentrations (IC50) on NO production were 754.68 ± 50.96, 1182.39 ± 22.10, 1527.83 ± 106.24 μg(herb)/mL, and ROS production were 311.70 ± 26.57, 332.64 ± 25.46, 917.60 ± 41.36 μg(herb)/mL for CC, CE and CI, respectively. The results indicated a certain similarity of CC and CE, as well as their significant difference from CI.

Perioperative risk factors, including the choice of anesthetics, may influence ovarian cancer recurrence after surgery. Inhalational anesthetic sevoflurane and intravenous agent propofol might affect cancer cell metabolism and signaling, which, in turn, may influence the malignancy of ovarian cancer cells. The different effects between sevoflurane and propofol on ovarian cancer cell biology and underlying mechanisms were studied. Cultured ovarian cancer cells were exposed to 2.5% sevoflurane, 4 μg/mL propofol, or sham condition as the control for 2 h followed by 24-h recovery. Glucose transporter 1 (GLUT1), mitochondrial pyruvate carrier 1 (MPC1), glutamate dehydrogenase 1 (GLUD1), pigment epithelium-derived factor (PEDF), p-Erk1/2, and hypoxia-inducible factor 1-alpha (HIF-1α) expressions were determined with immunostaining and/or Western blot. Cultured media were collected for

Oenococcus oeni and Lactiplantibacillus plantarum are major wine-associated lactic acid bacteria that positively influence wine by carrying out malolactic fermentation. O. oeni is the most widely used commercial starter in winemaking because of its fast and efficient malate metabolism capacity under harsh wine conditions. To date, very little is known about the specific molecular mechanism underlying the differences in malate metabolism between O. oeni and L. plantarum under harsh wine conditions. Therefore, in this study, the functions of genes encoding malic enzyme (ME) and malolactic enzyme (MLE) under acid stress in O. oeni and L. plantarum, previously described to have the ability to direct malate metabolism, were comparatively verified through genetic manipulation in L. plantarum. Results showed that the MLE was the only enzyme responsible for direct malate metabolism under acid stress in O. oeni and L. plantarum. In addition, the MLEs in O. oeni and L. plantarum were positively related to acid tolerance by metabolizing malate and increasing the medium pH. Furthermore, the MLE in O. oeni exhibited significantly higher malate metabolism activity than that in L. plantarum under acid stress.

Ordered lamellar superstructured zirconia (OLSZ) was successfully synthesized via a reflux-hydrothermal method. ZrOCl2, NaOH and methanol were used as zirconium source, precipitant and template, respectively. Methanol induced and directed the hierarchical structures: 0.57-nm thick ultrathin crystal framework, 1.14-nm periodic lamellar superstructure, several nanometers thick petal-like multilayered nanosheets, and flowers-like higher-level structure. OLSZ presented outstanding hierarchical thermostabilities up to 800 °C. The synthetic mechanism was proposed based on Gibbs theory and calculations. Compared with surfactant method, methanol template route presents many advantages, such as green, facile, efficient and low-cost, moreover the template is very easy to remove. This novel small molecule template strategy will be of great significance for the synthesis of other superstructured materials.

Background Acid stress is one of the most important environmental stresses that adversely affect the growth of lactic acid bacteria (LAB), such as Oenococcus oeni which was isolated from grape-berries and mainly used in wine fermentation. The aim of this paper is to comprehensively characterize the mechanisms of acid stress regulation in O. oeni and to provide a viable theoretical basis for breed and improvement of existing LAB. Method First, six O. oeni mutants with acid-sensitive (strains b2, a1, c2) and acid-tolerant (strains b1, a3, c1) phenotypes were screened from three wild-type O. oeni, and then their genome (sequencing), transcriptome and metabolome (LC-MS/MS) were examined. Results A total of 459 genes were identified with one or more intragenic single nucleotide polymorphisms (SNPs) in these mutants, and were extensively involved in metabolism and cellular functions with a high mutation rates in purine (46%) and pyrimidine (48%) metabolic pathways. There were 210 mutated genes that cause significant changes in expression levels. In addition, 446 differentially accumulated metabolites were detected, and they were consistently detected at relatively high levels in the acid-tolerant O. oeni mutant. The levels of intracellular differentially expressed genes and differential metabolites changed with increasing culture time. Conclusion The integrative pathways analysis showed that the intracellular response associated with acid regulation differed significantly between acid-sensitive and acid-tolerant O. oeni mutants, and also changed at different growth stages.

Background and Purpose: Surgery remains the first-line treatment of ovarian cancer. However, perioperative risk factors including the choice of anaesthetics may influence its recurrence after surgery. In the current study, it was hypothesised that inhalational anaesthetic sevoflurane and intravenous anaesthetic propofol might affect cancer cellular metabolism and signalling, which might interfere the malignancy of ovarian cancer cells. Experimental Approach: Cultured ovarian cancer cells were exposed to 2.5% sevoflurane or administered with 4 μg/mL propofol for 2 hours followed by 24 hours recovery. Their cell viability, proliferation, migration and invasion were assessed using cell counting kit-8, Ki-67 staining, wound healing and Transwell assay. Cellular signalling biomarkers were measured using immunofluorescent staining and/or Western blot. Cultured media were collected for 1H-NMR spectroscopy-based metabolomics analysis. Key Results: The cell viability, proliferation, migration, and invasion of ovarian cancer cells were enhanced by sevoflurane but suppressed by propofol. Sevoflurane increased the GLUT1, MPC1, GLUD1, p-Erk1/2, and HIF-1α expressions but decreased the PEDF expression. In contrast to the sevoflurane treatment, the “mirror changes” of these cellular markers were observed with propofol. Sevoflurane increased levels of isopropanol but decreased glucose and glutamine levels in the media, but the opposite changes of those metabolites were found after propofol treatment. Conclusion and Implications: These data indicated that unlike propofol, sevoflurane enhanced ovarian cancer cell metabolism and activated PEDF/Erk/HIF-1α cellular signalling pathway, suggesting that sevoflurane might have pro-tumour property but propofol might afford an anti-tumour property. The translational value of this work warrants further study.

To determine the short-term clinical outcomes of single-segment cervical spondylotic radiculopathy treated with posterior percutaneous endoscopic cervical discectomy (PPECD). Data of a total of 24 patients who underwent PPECD and local anesthesia for single-level segmental cervical spondylotic radiculopathy between March 2016 and December 2017 were reviewed. The Japanese Orthopaedic Association, visual analog scale (VAS), and neck disability index scores at preoperative 1 day, postoperative 1 day, 1 week, 1 month, 3 months, 6 months, and 1 year were recorded. The modified MacNab criteria at the last follow-up were re-recorded for the evaluation of clinical effectiveness. All operations were successfully completed under endoscopic guidance. No patient showed spinal cord, nerve root, vascular injuries, dural tears or other complications. The postoperative VAS scores of the arm and neck were significantly reduced compared with the preoperative VAS scores (P

Despite the great achievements of nanomedicines made in cancer chemotherapy, precise tumor targeting and deep penetration are still major challenges. Many nanomedicines can only passively accumulate near leaky site of tumor vessels through the enhanced permeability and retention (EPR) effect and cannot reach the deep region of tumor. To improve the tumor targeting, penetration and retention efficiency, an iRGD-mediated and enzyme-induced precise targeting gold nanoparticles system (iRGD/AuNPs-A&C) was developed by simply coadministering a tumor-homing penetration peptide iRGD (CRGDKGPDC) with a legumain responsive aggregable gold nanoparticle (AuNPs-A&C). In vitro, iRGD/AuNPs-A&C showed a consistent increase rate in size with AuNPs-A&C, suggesting that iRGD/AuNPs-A&C could also aggregate in the presence of legumain, which was in favor of the enhanced retention in tumor microenvironment. Meanwhile, iRGD/AuNPs-A&C showed higher 4T1 cells cellular uptake in vitro and presented higher penetration and accumulation in breast tumor in vivo than AuNPs-A&C, leading to enhanced tumor imaging efficacy and the improved chemotherapeutic effect to 4T1-bearing mice. These results suggested that the iRGD-mediated and enzyme-induced dual-functional nanoplatform was promising for the 4T1 tumor imaging and treatment.

BACKGROUND This study aimed to investigate the association between range of motion of the cervical vertebrae and various C5/C6 intervertebral space distraction heights. MATERIAL AND METHODS The cervical vertebrae from 6 fresh adult human cadavers were used to prepare the models. Changes in C4/C5 and C6/C7 intervertebral disk pressures, articular process pressure, and range of motion of the cervical vertebrae before and after the distraction of the C5/C6 intervertebral space at benchmark heights of 100%, 120%, 140%, and 160% were tested under different exercise loads. RESULTS The pressure on the adjacent intervertebral disks was highest with the standing upright position before distraction, varied with different positions of the specimens and distraction heights after distraction, and was closest to that before distraction at a distraction height of 120% (P

Hydrogels have been widely studied in various biomedical applications, such as tissue engineering, cell culture, immunotherapy and vaccines, and drug delivery. Peptide-based nanofibers represent a promising new strategy for current drug delivery approaches and cell carriers for tissue engineering. This review focuses on the recent advances in the use of self-assembling engineered β-sheet peptide assemblies for biomedical applications. The applications of peptide nanofibers in biomedical fields, such as drug delivery, tissue engineering, immunotherapy, and vaccines, are highlighted. The current challenges and future perspectives for self-assembling peptide nanofibers in biomedical applications are discussed.

A novel surface patterning nanorod (hydroxyapatite nano labyrinth, HANL), covered with labyrinthine nanogrooves on surface, was successfully synthesized with the assistance of tetrahydrofuran (THF). THF as the sole organic molecule not only promoted HA crystal growth, but also induced and stabilized the hierarchical nanorod. XRD results indicated that HANLs were of high phase purity and were well crystallized. SEM and TEM images showed that HANLs were of the length of 75–425 nm and the width of 20–85 nm, and were of 1-9-nm wide grooves covering over the surface which were also confirmed by the N2 adsorption analysis. The synthetic mechanism was proposed and explained in thermodynamics combined with theoretic calculations. This novel hierarchical HANLs may have great potential applications in bone replacement materials, composites, adsorbents, carriers, etc. This THF assisted synthetic strategy is green, low-cost, efficiently and surfactant-free, and may be useful in surface patterning other functional materials.

OBJECTIVES: To investigate the primary clinical value of atlantoaxial pedicle screw placement assisted by a modified 3D-printed navigation template. METHODS: We retrospectively analyzed the cases of 17 patients treated from June 2015 to September 2016 with atlantoaxial pedicle screw placement assisted by a modified 3D-printed navigation template. All procedures were performed prior to surgery, including thin-slice CT scanning, medical image sampling and computerized 3D modeling of the atlantoaxial joint, optimal pedicle screw trajectory determination, and anatomical trait acquisition for the atlantoaxial pedicle, spinous process of the axis, vertebral lamina and posterior lateral mass, and design of a reverse template. During surgery, a navigation template was tightly attached to the atlantoaxial joint to assist in pedicle screw placement. Surgeons subsequently used an electric drill to remove the template through a guide channel and then placed the atlantoaxial pedicle screw. Observed indexes included the VAS score, JOA improvement rate, surgery duration, and blood loss. RESULTS: Surgery was successful in all 17 patients, with an average operation duration of 106±25 min and an average blood loss of 220±125 ml. Three days postoperatively, the VAS score decreased from 6.42±2.21 to 3.15±1.26. Six months postoperatively, the score decreased to 2.05±1.56. The postoperative JOA score increased significantly from 7.68±2.51 to 11.65±2.72 3 d after surgery and to 13.65±2.57 after 6 months. Sixty-eight pedicle screws were inserted successfully, with 34 in the atlas and 34 in the axis. According to the Kawaguchi standard, 66 screws were in grade 0 (97.06%), and 2 were in grade 1 (2.94%). The pre- and postoperative transverse and sagittal screw angles showed no significant differences. CONCLUSIONS: Atlantoaxial pedicle screw placement assisted by a modified 3D-printed navigation template is worth recommending due to the improved accuracy in screw placement, improved patient safety and beneficial clinical effects.

Platinum(iv) prodrugs of clinically used cisplatin and oxaliplatin with two axial long lipid chains were developed for nanoparticle delivery to combat cisplatin resistance.

Carbon nanodots (CDs) have been exhibiting increasing applications owing to their luminescence properties and biocompatibility as imaging probes in diagnosis. However, poor tumor targeting and penetration of CDs is still the biggest challenge limiting their tumor imaging efficacy. To improve the tumor targeting and penetration efficiency of CDs, we developed an active tumor targeting imaging system by simply fabricating a tumor-homing penetration peptide iRGD (CRGDKGPDC) to red shift emissive CDs (iRGD-CDs) with a physical method. Particularly, iRGD-CDs showed a small size and red shift fluorescence signals as CDs, which made iRGD-CDs suitable for in vivo fluorescence imaging. iRGD-CDs showed higher cellular uptake in vitro, while presented higher penetration and accumulation in tumor tissue in vivo, leading to better tumor imaging efficacy. In conclusion, decoration with iRGD could significantly increase the permeability of CDs in tumor vessels and tumor tissue, generating more CDs leaking out from tumor vasculature, consequently improving the sensitivity of tumor imaging.

Sustained-release systems made by biodegradable polymers for protein and peptide drug delivery have received considerable attention by academic researchers and major pharmaceutical companies around the world. Various types of biodegradable materials, including natural and synthetic polymers, have been applied to form protein and peptide drug carriers. Among these material candidates, poly lactic acid (PLA) and poly lactic-co-glycolic acid (PLGA) are the most commonly used biodegradable materials in the development of protein and peptide microspheres. In addition, many microsphere preparation technologies, including spray drying, coacervation, multiple emulsion solvent evaporation method and microporous membrane emulsification have been developed for microspheres preparation. In this review, we particularly summarize and briefly introduce the materials and methods that are used to fabricate microspheres as protein delivery systems. The existing opportunities and challenges for successful protein delivery are also discussed.

Boron, an essential plant micronutrient, was effective in the form of potassium tetraborate for control of postharvest gray mold caused by Botrytis cinerea on table grapes stored at room temperature or at 0 degrees C. The inhibition of fruit decay was closely correlated with boron concentrations and partially influenced by pH value of the solution. Boron strongly inhibited spore germination, germ tube elongation, and mycelial spread of B. cinerea in the culture medium. Application of boron at 1% caused the appearance of abnormal spores (disrupted) in some cases. By using propidium iodide fluorescent staining, loss of membrane integrity in B. cinerea was observed after boron treatment. Furthermore, boron led to the leakage of cellular constituents (soluble proteins and carbohydrates) from hyphae of B. cinerea. These data suggest that the mechanisms by which boron decreased gray mold decay of table grapes may be directly related to the disruption effect of boron on cell membrane of the fungal pathogen that resulted in the breakdown of the cell membrane and loss of cytoplasmic materials from the hyphae.

This paper propose a method to deal with the complex nonlinear characteristics, which was caused by the uncertainty of the unknown. As the received signal strength is low in Non line-of-sight environment, the proposed algorithm can be used to process and predict the unknown nodes position by maximum likelihood estimation method. Furthermore, experimental results show that the mobile target tracking error can be less than 1m when we use the method mentioned above, thus meeting the requirements of smart space mobile targeting.