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Xun Huang,1,2 Jiexiang He,2,3 Huan-tian Zhang,1 Kai Sun,2,3 Jie Yang,1 Huajun Wang,1 Hongxin Zhang,2,3 Zhenzhao Guo,2,3 Zhen-gang Zha,1 Changren Zhou2,31Department of Bone and Joint Surgery, The First Affiliated Hospital of Jinan University, 2Department of Materials Science and Engineering, Jinan University, 3Engineering Research Center of Artificial Organs and Materials, Ministry of Education, Guangzhou, ChinaAbstract: CD44 ligand–receptor interactions are known to be involved in regulating cell migration and tumor cell metastasis. High expression levels of CD44 correlate with a poor prognosis of melanoma patients. In order to understand not only the mechanistic basis for dacarbazine (DTIC)-based melanoma treatment but also the reason for the poor prognosis of melanoma patients treated with DTIC, dynamic force spectroscopy was used to structurally map single native CD44-coupled receptors on the surface of melanoma cells. The effect of DTIC treatment was quantified by the dynamic binding strength and the ligand-binding free-energy landscape. The results demonstrated no obvious effect of DTIC on the unbinding force between CD44 ligand and its receptor, even when the CD44 nanodomains were reduced significantly. However, DTIC did perturb the kinetic and thermodynamic interactions of the CD44 ligand–receptor, with a resultant greater dissociation rate, lower affinity, lower binding free energy, and a narrower energy valley for the free-energy landscape. For cells treated with 25 and 75 µg/mL DTIC for 24 hours, the dissociation constant for CD44 increased 9- and 70-fold, respectively. The CD44 ligand binding free energy decreased from 9.94 for untreated cells to 8.65 and 7.39 kcal/mol for DTIC-treated cells, which indicated that the CD44 ligand–receptor complexes on DTIC-treated melanoma cells were less stable than on untreated cells. However, affinity remained in the micromolar range, rather than the millimolar range associated with nonaffinity ligands. Hence, the CD44 receptor could still be activated, resulting in intracellular signaling that could trigger a cellular response. These results demonstrate DTIC perturbs, but not completely inhibits, the binding of CD44 ligand to membrane receptors, suggesting a basis for the poor prognosis associated with DTIC treatment of melanoma. Overall, atomic force microscopy-based nanoscopic methods offer thermodynamic and kinetic insight into the effect of DTIC on the CD44 ligand-binding process.Keywords: atomic force microscopy, tumor, dynamic force spectroscopy, kinetic and thermodynamic interactions, affinity, nanoindentation

The full mechanism of action of propofol, a commonly administered intravenous anesthetic drug in clinical practice, remains elusive. The focus of this study was the role of GABAergic neurons which are the main neuron group in the ventral pallidum (VP) closely associated with anesthetic effects in propofol anesthesia. The activity of VP GABAergic neurons following propofol anesthesia in Vgat-Cre mice was observed via detecting c-Fos immunoreactivity by immunofluorescence and western blotting. Subsequently, chemogenetic techniques were employed in Vgat-Cre mice to regulate the activity of VP GABAergic neurons. The role of VP GABAergic neurons in generating the effects of general anesthesia induced by intravenous propofol was further explored through behavioral tests of the righting reflex. The results revealed that c-Fos expression in VP GABAergic neurons in Vgat-Cre mice dramatically decreased after propofol injection. Further studies demonstrated that chemogenetic activation of VP GABAergic neurons during propofol anesthesia shortened the duration of anesthesia and promoted wakefulness. Conversely, the inhibition of VP GABAergic neurons extended the duration of anesthesia and facilitated the effects of anesthesia. The results obtained in this study suggested that regulating the activity of GABAergic neurons in the ventral pallidum altered the effect of propofol on general anesthesia., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024. Published by Elsevier Ltd.)

The basolateral amygdala (BLA) is the subregion of the amygdala located in the medial of the temporal lobe, which is connected with a wide range of brain regions to achieve diverse functions. Recently, an increasing number of studies have focused on the participation of the BLA in many neuropsychiatric disorders from the neural circuit perspective, aided by the rapid development of viral tracing methods and increasingly specific neural modulation technologies. However, how to translate this circuit-level preclinical intervention into clinical treatment using noninvasive or minor invasive manipulations to benefit patients struggling with neuropsychiatric disorders is still an inevitable question to be considered. In this review, we summarized the role of BLA-involved circuits in neuropsychiatric disorders including Alzheimer's disease, perioperative neurocognitive disorders, schizophrenia, anxiety disorders, depressive disorders, posttraumatic stress disorders, autism spectrum disorders, and pain-associative affective states and cognitive dysfunctions. Additionally, we provide insights into future directions and challenges for clinical translation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Pikas (Lagomorpha: Ochotonidae) are small mouse-like lagomorphs. To investigate their adaptation to different ecological environments during their dispersal from the Qinghai-Xizang (Tibet) Plateau (QTP), we collected 226 pikas and measured 20 morphological characteristics and recorded habitat information. We also sequenced the genome of 81 specimens, representing 27 putative pika species. The genome-wide tree based on 4 090 coding genes identified five subgenera, i.e., Alienauroa , Conothoa , Lagotona , Ochotona , and Pika , consistent with morphometric data. Morphologically, Alienauroa and Ochotona had similar traits, including smaller size and earlier divergence time compared to other pikas. Consistently, the habitats of Alienauroa and Ochotona differed from those of the remaining subgenera. Phylogenetic signal analysis detected 83 genes significantly related to morphological characteristics, including several visual and hearing-related genes. Analysis of shared amino acid substitutions and positively selected genes (PSGs) in Alienauroa and Ochotona identified two genes, i.e., mitochondrial function-related TSFM (p.Q155E) and low-light visual sensitivity-related PROM1 (p.H419Y). Functional experiments demonstrated that TSFM-155E significantly enhanced mitochondrial function compared to TSFM-155Q in other pikas, and PROM1-419Y decreased the modeling of dynamic intracellular chloride efflux upon calcium uptake. Alienauroa and Ochotona individuals mostly inhabit different environments (e.g., subtropical forests) than other pikas, suggesting that a shift from the larger ancestral type and changes in sensory acuity and energy enhancement may have been required in their new environments. This study increases our understanding of the evolutionary history of pikas.

Previous studies have reported that circular RNAs (circRNAs) play a key role in the pathogenesis and progression of various diseases. In the present study, we aimed to identify potential circRNAs associated with the progression of hepatocellular carcinoma (HCC) after insufficient radiofrequency ablation (IRFA). A xenograft mouse IRFA model was initially established, and immunohistochemical staining (IHC) and polymerase chain reaction (PCR) were performed to confirm the expression of programmed cell death-ligand 1 (PD-L1) and vascular endothelial growth factor receptor-1 (VEGFR-1). CircRNA expression alterations were screened by next-generation sequencing (RNA-seq). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to predict the function of genes coding differentially expressed circRNAs. The selected circRNAs were validated utilizing PCR and Sanger sequencing. The relationships between circRNAs, microRNAs, PD-L1, and VEGFR-1 were predicted by bioinformatics. Overall, a total of 612 circRNAs were differentially expressed in IRFA-treated subcutaneous tumorigenesis tissue. Among them, 435 circRNAs were significantly upregulated and 177 circRNAs were downregulated. GO and KEGG analyses were employed to predict the functions of these circRNAs. Thereafter, quantitative reverse transcription PCR (qRT-PCR) assays determined that these seven circRNAs were overexpressed in the IRFA group, which was consistent with the RNA-seq results. Based on the bioinformatic analysis, seven circRNAs confirmed by Sanger sequencing were predicted to likely regulate PD-L1 and VEGFR-1 expression levels by functioning as sponges for microRNAs (miRNAs) and forming a circRNA-miRNA-PD-L1/VEGFR-1 regulatory network. Finally, IHC and qRT-PCR of PD-L1 and VEGFR-1 confirmed the activation of this pathway. Taken together, we report that differentially expressed circRNAs might simultaneously regulate PD-L1 and VEGFR-1 in the IRFA tissues, which provides a novel view of circRNAs in HCC progression after the IRFA procedure.

DNA N6-methyladenine (6 mA) is a new type of DNA methylation identified in various eukaryotic cells. However, its alteration and genomic distribution features in hepatocellular carcinoma (HCC) remain elusive. In this study, we found that N6AMT1 overexpression increased HCC cell viability, suppressed apoptosis, and enhanced migration and invasion, whereas ALKBH1 overexpression induced the opposite effects. Further, 23,779 gain-of-6 mA regions and 11,240 loss-of-6 mA regions were differentially identified in HCC tissues. The differential gain and loss of 6 mA regions were considerably enriched in intergenic regions. Moreover, 7% of the differential 6 mA modifications were associated with tumors, with 60 associated with oncogenes and 57 with tumor suppressor genes (TSGs), and 17 were common to oncogenes and TSGs. The candidate genes affected by 6 mA were filtered by gene ontology (GO) and RNA-seq. Using quantitative polymerase chain reaction (qPCR), BCL2 and PARTICL were found to be correlated with DNA 6 mA in certain HCC processes., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Blood lead poisoning is a universal and severe health problem that greatly threatens human health in various industries. Elimination of blood lead relying on chelating agents and combination with hemoperfusion adsorbents has achieved considerable progress, but it is still suffering from the compromised selectivity of adsorbents as well as in absence of real time monitoring during treatment. Herein, we proposed a selective blood lead adsorbent integrated with real-time visualized/electrochemical bi-modal monitoring based on TMPyP-bound guanosine-borate (GB) supramolecular hydrogel as potential smart hemoperfusion device. The GB hydrogel possessed stability in physiological environment, self-healing ability resistant to fluid shear, blood compatibility, selective adsorption of lead ions superior to conventional adsorbents, anti-fouling performance to blood components and renewability. Benefiting from binding with TMPyP and the intrinsic conductivity, GB hydrogel was endowed with the ability to qualitatively diagnose the presence of blood lead via simple color change and quantitatively reflect the amount of adsorbed lead from blood accurately through electrochemical technique. This work puts forward an integrated treatment/monitoring hemoperfusion device with high selectivity, simple fabrication and low-cost, providing a paradigm for next generation design of intelligent, monitorable theranostic hemopurification system, which is also an extensible platform for the other research fields such as environmental monitoring and remediation., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The prevalence of colorectal cancer (CRC) and type 2 diabetes mellitus (T2DM) is increasing globally. It is rarely noticed that the incidence of CRC is higher in patients with T2DM. What needs to be mentioned is that metformin, a commonly used clinical drug for T2DM, attracts scholars' attention because of its benefits in lowering the risk of developing CRC. Hence, we try to find the common grounds of initiation of T2DM and CRC and the reason why metformin reduces the risk of CRC in patients with T2DM. We noticed consistent changes of gut microbiota, such as elevated Bacteroides, Prevotella and Bifidobacterium and depressed Firmicutes and Lactobacillus . Furthermore, many studies in recent years have proved that the efficacy of metformin, such as improving blood glucose, depends on the gut microbiota. Coincidentally, the progression of CRC is inseparable from the contributions of gut microbiota. Therefore, we first proposed the concept of the metformin-gut microbiota-CRC (in T2DM) axis to explain the effect of metformin in reducing CRC in patients with T2DM . In this review, we elaborated the new concept and its potential clinical application value., Competing Interests: Conflict-of-interest statement: There is no conflict of interest associated with any of the senior author or other coauthors contributed their efforts in this manuscript., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Increasing evidence confirms that exosome-mediated transfer of microRNAs can influence cancer progression including tumor cell invasion, cell proliferation, and drug resistance via cell-cell communication. However, the potential role of exosomal-miR-1260b in lung adenocarcinoma (LAC) remains poorly understood. Thus, this study focused on investigating the function of exosomal-miR-1260b on cell invasion. Exosomal-miR-1260b was found to be higher in plasma of patients with LAC than that of healthy persons via quantitative real-time polymerase chain reaction assay. The sensitivity and specificity of exosomal-miR-1260b (cutoff point: 2.027) were 72% and 86%, and area under the curve of 0.845 (95% CI = 0.772-0.922). Elevated expression of miR-1260b in LAC tissues was positively correlated with exosomal-miR-1260b in plasma (r = .642, p < .05). Furthermore, ceramide biosynthesis regulated exosomal-miR-1260b secretion. Exosome-mediated transfer of miR-1260b promoted A549 cell invasion and was still functional inside A549 cells. Moreover, exosomal-miR-1260b regulated Wnt/β-catenin signaling pathway by inhibiting sFRP1 and Smad4. This study identified a new regulation mechanism involving in cell invasion by exosome-mediated tumor-cell-to-tumor-cell communication. Targeting exosome-microRNAs may provide new insights into the diagnosis and treatment of LAC., (© 2020 Wiley Periodicals, Inc.)

Background: Culture is still the gold standard for the detection of genital mycoplasma which could cause urogenital infections in humans. Mycoplasma IST2 is a commercial kit widely used for the detection of M. hominis and Ureaplasma species. Its accuracy was partially impaired because clinical specimens are usually mixed with purulent or transparent mucus. We aimed to solve this problem through sample homogenization by N -acetylcysteine (NAC) treatment., Methods: Twenty-two endocervical swab samples were collected from 22 female patients with suspected mycoplasma infection, while 11 of these specimens were with purulent or transparent mucus. Mycoplasma IST2 testing kit was used for mycoplasma culture and AST for the control group and NAC-treated group., Results: Genital mycoplasma was detected in 15 of 22 samples for both groups. The colony number in 6 out of 11 purulent specimens (54.5%) was more than 10 4  CFU/ml of genital mycoplasma for the NAC-treated group, while only one of 11 (9.1%) for the control group. For the nonpurulent specimens, no significant difference had been found in colony counting of genital mycoplasma between the control group and NAC-treated group ( P > 0.05). The results of antimicrobial susceptibility testing for the NAC-treated group were highly similar to those for the control group., Conclusions: Our results demonstrate that NAC is helpful in sample homogenization and NAC treatment can improve the detection efficiency of mycoplasma with Mycoplasma IST2 testing., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Xin-Ru Mao et al.)

The deregulation of exosomal microRNAs (miRNAs) plays an important role in the progression of hepatocarcinogenesis. In this study, we highlight exosomes as mediators involved in modulating miRNA profiles in liver cancer cells after induction of the epithelial-mesenchymal transition (EMT) and metastasis. Initially, we induced EMT in a hepatocellular carcinoma cell (HCC) line (Hep3B) by stimulation with transforming growth factor-β (TGF-β) and confirmed by western blot detection of EMT markers such as vimentin and E-cadherin. Exosomes were then isolated from the cells and identified by nanoparticle tracking analysis (NTA). The isolated exosomal particles from unstimulated Hep3B cells (Hep3B exo) or TGF-β-stimulated EMT Hep3B cells (EMT-Hep3B exo) contained higher levels of exosome marker proteins, CD63 and TSG101. After incubation with EMT-Hep3B exo, Hep3B cell proliferation increased. EMT-Hep3B exo promoted the migration and invasion of Hep3B and 7721 cells. High-throughput sequencing of miRNAs and mRNA within the exosomes showed 119 upregulated and 186 downregulated miRNAs and 156 upregulated and 166 downregulated mRNA sequences in the EMT-Hep3B exo compared with the control Hep3B exo. The most differentially expressed miRNAs and target mRNA sequences were validated by RT-qPCR. Based on the known miRNA targets for specific mRNA sequences, we hypothesized that GADD45A was regulated by miR-374a-5p. Inhibition of miR-374a-5p in Hep3B cells resulted in exosomes that inhibited the proliferation, migration, and invasion of HCC cells. These results enhance our understanding of metastatic progression of liver cancer and provide a foundation for the future development of potential biomarkers for diagnosis and prognosis of hepatic cancer., Competing Interests: None., (AJTR Copyright © 2020.)

Objectives: To explore the feasibility of preoperative prediction of vascular invasion (VI) in breast cancer patients using nomogram based on multiparametric MRI and pathological reports., Methods: We retrospectively collected 200 patients with confirmed breast cancer between January 2016 and January 2018. All patients underwent MRI examinations before the surgery. VI was identified by postoperative pathology. The 200 patients were randomly divided into training (n = 100) and validation datasets (n = 100) at a ratio of 1:1. Least absolute shrinkage and selection operator (LASSO) regression was used to select predictors most associated with VI of breast cancer. A nomogram was constructed to calculate the area under the curve (AUC) of receiver operating characteristics, sensitivity, specificity, accuracy, positive prediction value (PPV) and negative prediction value (NPV). We bootstrapped the data for 2000 times without setting the random seed to obtain corrected results., Results: VI was observed in 79 patients (39.5%). LASSO selected 10 predictors associated with VI. In the training dataset, the AUC for nomogram was 0.94 (95% confidence interval [CI]: 0.89-0.99, the sensitivity was 78.9% (95%CI: 72.4%-89.1%), the specificity was 95.3% (95%CI: 89.1%-100.0%), the accuracy was 86.0% (95%CI: 82.0%-92.0%), the PPV was 95.7% (95%CI: 90.0%-100.0%), and the NPV was 77.4% (95%CI: 67.8%-87.0%). In the validation dataset, the AUC for nomogram was 0.89 (95%CI: 0.83-0.95), the sensitivity was 70.3% (95%CI: 60.7%-79.2%), the specificity was 88.9% (95%CI: 80.0%-97.1%), the accuracy was 77.0% (95%CI: 70.0%-83.0%), the PPV was 91.8% (95%CI: 85.3%-98.0%), and the NPV was 62.7% (95%CI: 51.7%-74.0%). The nomogram calibration curve shows good agreement between the predicted probability and the actual probability., Conclusion: The proposed nomogram could be used to predict VI in breast cancer patients, which was helpful for clinical decision-making., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Circular RNAs have recently been disclosed as potential biomarkers for human cancers. This study aimed to characterize the expression and function of a novel circular RNA, circCDK13, in liver cancer progression, as well as to elucide the underlying mechanisms. For this purpose, circCDK13 expression was quantitatively analyzed by RT-PCR in various liver cancer cell lines and human cancerous tissues. The migration, cell cycle progression, proliferation and invasion of liver cancer cells with an enhanced circCDK13 expression were evaluated by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay, flow cytometry and the Transwell culture system. Microarray and western blot analyses were performed to explore the underlying signaling mechanisms. The role of circCDK13 in liver cancer was finally examined by tumorigenicity assay using nude mice. The results revealed that circCDK13 expression was suppressed in various liver cancer lines and tissue samples from patients with liver cancer (hepatocellular carcinoma). The induced overexpression of circCDK13 in the liver cancer cells markedly inhibited their migration rates, altered cell cycle progression, and suppressed the cell migratory and invasive capacities. Microarray analysis also identified numerous downstream genes regulated by circCDK13, particularly those in the Janus tyrosine kinase (JAK)/signal transducer and activator of transcription (STAT) and phosphoinositide 3-kinase (PI3K)/AKT signaling pathways. The results of the tumorigenicity assay revealed that circCDK13 overexpression significantly inhibited liver cancer progression in nude mice. On the whole, the findings of this study indicate that circCDK13 is a novel circular RNA that suppresses liver cancer progression, and that these suppressive effects are possibly mediated via the JAK/STAT and PI3K/AKT signaling pathways.

This study explored the effects of mulching straw mat, agricultural carpet, transparent-plastic film and horticultural fabric on nitrification-denitrification, nitrate reductase (NR), nitrite reductase (NiR), ammonium, nitrate and nitrite nitrogen in root-zone soil grown with three-year old apple trees (Malus domestica cv. Starkrimson) during summer and autumn. Results showed that the four treatments decreased nitrification intensity in summer soil, NiR activity in summer-autumn soil and the variation coefficient of nitrification-denitrification intensity and NR in both summer and autumn soil. The treatments increased the denitrification intensity, NR activity, ammonium nitrogen contents in summer-autumn soil and ammonium nitrogen contents in autumn soil. Straw mat treatment increased denitrification intensity and nitrate nitrogen contents in both summer and autumn soil and decreased the activity of NR and NiR in summer soil. The coefficient of variation of nitrification-denitrification intensity and NR activity treated by mulching straw mat was lower than those in the other treatments in both summer and autumn soil. Agricultural carpet increased the NR and NiR activity in summer soil, the nitrate nitrogen contents in summer-autumn soil and the denitrification intensity in autumn soil and decreased denitrification intensity in summer soil. Transparent-plastic film increased the nitrite nitrogen contents in summer soil, the contents of nitrate nitrogen in summer-autumn soil, the nitrification intensity and NiR activity in autumn soil, and decreased nitrate nitrogen contents in summer soil. Horticultural fabric increased denitrification intensity in summer soil, nitrification intensity in summer-autumn and autumn soil and the nitrate nitrogen contents in autumn soil. The four mulching treatments all promoted plant growth. In the four mulching treatments, the new shoot and trunk thickening growth were more under straw mat and horticultural fabric treatments. The four mulching treatments had different effects on nitrate metabolism in summer and autumn soil, but they were able to stabilize the soil nitrate metabolism and transformation. Among the treatments, straw mat had the best stable effect.

The interaction between cells and biomaterials plays a key role in cell proliferation and differentiation in tissue engineering. However, a quantitative analysis of those interactions has been less well studied. The objective of this study was to quantitative recapitulate the difference of MC3T3-E1 cell adhesion, morphological and biomechanical properties on chitosan-collagen films in terms of chemical composition. Here, the unbinding force between MC3T3-E1 cell and a series of chitosan-collagen films was probed by a real-time and in situ atomic force microscopy-single cell force spectroscopy (AFM-SCFS). Meanwhile, changes in cell morphology and Young's modulus on different chitosan-collagen films were detected by AFM. The cell area and CCK-8 results showed that cell spreading and proliferation increased with increasing collagen content. AFM observations clearly showed cell height decreased and pseudopod fusion with the collagen content increased. Cell adhesive force increased from 0.76±0.17 nN to 1.70±0.19 nN. On the contrary, cells Young's modulus, which reflected biophysical changes of cells decreased from 11.94±3.19 kPa to 1.81±0.52 kPa, respectively. It suggested that stronger cell-substrate interactions benefit cell adhesion, and better cell flexibility improve cell spreading. The findings indicate that cell morphology, adhesive force and Young's modulus are significant affected by various chitosan-collagen substrates. Those methods and quantitative results have guiding significance for investigating the mechanism of chitosan and/or collagen based cell-targeting drug carrier and the preparation of chitosan-collagen composite biomaterials., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objective: To investigate the role of transient receptor potential melastatin 8 (TRPM8) channels in migraine mechanism in rats by measuring the changes in expression of TRPM8 in the trigeminal nerve of rats with migraine., Methods: Twenty male Sprague-Dawley rats were randomly and equally divided into a blank control group and a model group. Nitroglycerin (10 mg/kg) was injected subcutaneously in the back of the neck once a week for 5 weeks, to prepared a rat model of migraine without aura. Normal saline was injected subcutaneously instead of nitroglycerin in the control group. At 4 hours after the final injection, behavior scoring of all rats was performed, and then the trigeminal nerve ganglions of rats in both groups were collected for measurement of expression of N-methyl-D-aspartate receptor (NMDAR), protein kinase A (PKA), and TRPM8 using immunohistochemical staining, immunofluorescence, and Western blot, respectively., Results: The behavior score in each week during the rat model preparing was significantly higher in the model group than in the control group (P<0.05). The expression of NMDAR, PKA, and TRPM8 in the model group was significantly higher than in the control group (P<0.01). Both the behavior score and the expression of NMDAR were positively correlated with the expression of TRPM8 (r=0.822 and 0.794 respectively; P<0.01)., Conclusions: TRPM8 may be involved in migraine mechanism probably by activation of the NMDAR pathway.

Distraction osteogenesis after aggrieved bone segment resections is promising in the treatment of bone tumors and osteomyelitis. However, there is ambiguity with regard to the optimal choice of bone substitute, with biodegradability and excellent bone repair performance constituting key requirements. The purpose of this study was to develop a novel resorbable strontium-containing α-calcium sulfate hemihydrate (Sr-CaS) bone substitute to provide an alternative option for surgeons that better meets these requirements. The Sr-CaS was prepared using co-precipitation and hydrothermal methods and analyzed using x-ray diffraction (XRD), Fourier transform infrared (FTIR) scanning and thermogravimetric differential scanning calorimeter (TG-DSC) patterns. Cytotoxicity by tetrazolium bromide (MTT), sub-acute toxicity and hemolysis tests were performed to assess the initial biocompatibility of the new bone substitute. Radiographic analysis, micro-CT measurements and histological observation were used to evaluate the bone repair ability in rat tibia bone defects. The XRD and FTIR patterns of Sr-CaS were both very similar to CaS and the product had comparable characteristics similar to α-CaS as demonstrated by TG-DSC. Cytotoxicity of the substitute was class 1 (no cytotoxicity) and hemolysis was 4.3% (no hemolysis). Sub-acute toxicity was not seen after a 14 day evaluation. The substitute was radio-opaque. The empty group exhibited the lowest levels of both bone mineral densities (BMD) and bone volume/total volume (BV/TV) of the defects when compared to all other groups. The two Sr-CaS groups resulted in significantly greater BMDs and BV/TV of the defect compared to the CaS only group. However, there was no significant difference between the 5% and 10% Sr-CaS groups. The Sr-CaS was resorbable with satisfactory biocompatibility. The doped strontium ions enhanced the bone repair performance of CaS in a rat model and the new substitute demonstrated promising results for clinical use.

In order to improve the bonding between halloysite nanotubes (HNTs) and poly(L-lactide) (PLLA), and hence to increase the mechanical properties of HNTs/PLLA nano-composite, HNTs were surface-grafted with PLLA under microwave irradiation and then blended with PLLA matrix. The optimal conditions for grafting polymerization are: irradiation time of 30 min, microwave power of 30 W and reaction temperature of 130 degrees C. The structure and properties of the surface-grafted HNTs (g-HNTs) were characterized by Fourier transformation infrared (FTIR), thermal gravimetric analysis (TGA), X-ray diffraction (XRD) and dynamic light scattering (DLS). Nano-composites of g-HNTs/PLLA and non-grafted HNTs/PLLA were subsequently evaluated in terms of crystallinity, dispersion, interfacial interaction, mechanical performance and cytocompatibility by polarized optical microscopy (POM), field scanning electron microscope (FESM), tensile testing and cell culture experiment. Results show that the grafted PLLA chains on the surfaces of HNTs, as inter-tying molecules, played an important role in improving the adhesive strength between the nanotubes and the polymer matrix. The enhanced interaction among g-HNTs and PLLA matrix resulted in a better tensile strength and modulus compared to the pristine PLLA and HNTs/PLLA. Cell culture results indicated that g-HNTs promoted both adhesion and proliferation of M3T3 fibroblasts on the g-HNTs/PLLA composite film.

Biomimetic composites consisting of polymer and mineral components, resembling bone in structure and composition, were produced using a rapid prototyping technique for bone tissue engineering applications. Solid freeform fabrication, known as rapid prototyping (RP) technology, allows scaffolds to be designed with pre-defined and controlled external and internal architecture. Using the indirect RP technique, a three-component scaffold with a woodpile structure, consisting of poly-L-lactic acid (PLLA), chitosan and hydroxyapatite (HA) microspheres, was produced that had a macroporosity of more than 50% together with micropores induced by lyophilization. X-ray diffraction analysis indicated that the preparation and construction of the composite scaffold did not affect the phase composition of the HA. The compressive strength and elastic modulus (E) for the PLLA composites are 0.42 and 1.46 MPa, respectively, which are much higher than those of chitosan/HA composites and resemble the properties of cellular structure. These scaffolds showed excellent biocompatibility and ability for three-dimensional tissue growth of MC3T3-E1 pre-osteoblastic cells. The pre-osteoblastic cells cultured on these scaffolds formed a network on the HA microspheres and proliferated not only in the macropore channels but also in the micropores, as seen from the histological analysis and electron microscopy. The proliferating cells formed an extracellular matrix network and also differentiated into mature osteoblasts, as indicated by alkaline phosphatase enzyme activity. The properties of these scaffolds indicate that they can be used for non-load-bearing applications., (Copyright 2009 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Objective: To prepare morphine-loaded chitosan microspheres by emulsion ionic cross-linking and investigate the effect of initial morphine quantity and different cross-linking degrees on drug loading, encapsulation efficiency and in vitro drug release., Methods: Chitosan (with a relative molecular mass of 50,000 and deacetylation degree no less than 90%) at 100 mg and morphine at 20, 30, 40, or 50 mg were dissolved by 2% acetate and dripped slowly into 15 ml soy-bean oil containing 0.75 ml Span80. After full emulsification at 35 degrees C; for 1.5 h, the mixture was dripped slowly into sodium tripolyphosphate (10 mg/ml) at the mass ratio of 5:1, 7:1, or 9:1 to allow cross-linking for 2 h. The drug loading, encapsulation efficiency and in vitro drug release of the preparations were measured., Results: The drug loading in the microsphere increased while the encapsulation efficiency reduced with the increment of the initial morphine quantity. High cross-linking degree resulted in prolonged release time of the drug loaded in the preparations., Conclusion: The microspheres loaded with morphine allows sustained release of morphine.

The potential energy surface of the H(2)/S(2) system has been characterized at the full valence MRCI+Davidson/aug-cc-pV(Q+d)Z level of theory using geometries optimized at the MRCI/aug-cc-pVTZ level. The analysis includes channels occurring entirely on either the singlet or the triplet surface as well as those involving an intersystem crossing. RRKM-based multiple well calculations allow the prediction of rate constants in the temperature range of 300-2000 K between 0.1 and 10 bar. Of the SH recombined on the singlet surface, the stabilization of the rovibrationally excited adduct HSSH is at the low-pressure limit at 1 bar, but it has a rate comparable to that forming another major set of products H(2)S + S (via an intersystem crossing) at temperatures below 1000 K; at higher temperatures, HSS + H becomes the dominant product. For the reaction H(2)S + S, the presence of an intersystem crossing allows the formation of the singlet excited adduct H(2)SS, most of which rearranges and stabilizes as HSSH under atmospheric conditions. At high temperatures, the majority of excited HSSH dissociates to SH + SH and HSS + H. Compared to reported shock tube measurements of the reaction H(2)S + S, most of the S atom consumption can be described by the triplet abstraction route H(2)S + S --> SH + SH, especially at high temperatures, but inclusion of the singlet insertion channel provides a better description of the experimental data. The reaction HSS + H was found to proceed predominantly on the singlet surface without a chemical barrier. The formation of the major product channel SH + SH is very fast at room temperature (approximately 4 x 10(15) cm(3) mol(-1) s(-1)). While the formation of H(2)S + S or S(2) + H(2) via an isomerization or an intersystem crossing, respectively, are minor product channels, their rates are significantly higher than those of the corresponding direct triplet channels, except at elevated temperatures. Finally, due to the relatively shallow nature of its well, the stabilization of H(2)SS is negligible under conditions of likely interest.

Objective: To investigate the adsorption behavior of enamel matrix proteins (EMPs) on the enamel surface and study their effect on biomineralization of enamel using quartz crystal microbalance (QCM) technique., Methods and Results: The EMPs were adsorbed on the enamel surface to form a protein film, which was soaked in simulated body fluid solutions. After 30 days of biomimetic mineralization, the hydroxyapatite nucleation, growth and aggregation occurred with hydroxyapatite crystal formation on the enamel surface., Conclusion: The EMPs play a key role in regulating enamel mineralization.

The reaction of SH + O2 has been characterized using multireference methods, with geometries and vibrational frequencies determined at the CASSCF/cc-pVTZ level and single-point energies calculated at the MRCI/aug-cc-pV(Q+d)Z level. The dominant product channels are found to be SO + OH and HSO + O. Whereas the formation of SO + OH has a barrier of approximately 81 kJ mol-1, it is energetically more favorable than the formation of HSO + O, which is barrierless beyond the endothermicity of approximately 89 kJ mol-1 at 0 K. Thus, the reaction SH + O2 --> SO + OH is 2 orders of magnitude faster than the reaction SH + O2 --> HSO + O at room temperature, revealing that the atmospheric oxidation of SH leads directly to the formation of SO + OH with the rate coefficient of approximately 1.0 x 10(-2) cm3 mol-1 s-1. At temperatures above 1000 K, however, the rates of the two channels become comparable. This may be attributed to the entropy effects leading to the higher pre-exponential factor for the channel (forming HSO + O) via a more loose transition state than that (forming SO + OH) entailing a four-centered transition state. Whereas the hydrogen abstraction reaction producing S + HO2 is found to proceed on the quartet surface, the substantial barrier of approximately 165 kJ mol-1 means that it occurs as a minor product channel. Finally, the formation of possible products SO2 + H is prohibited due to the lack of a transition state for the direct sulfur insertion.

Biomimetic polymeric nanofibres are of great interest in tissue engineering and wound repair because of their structural similarity to extracellular matrix. In this work, biomimetic chitosan-based nanofibres with various diameters were prepared by ionically cross-linking with tripolyphosphate (TPP) in adipic acid medium and characterised using transmission electron microscopy, X-ray diffraction and Fourier-transform infrared spectroscopy. Using dexamethasone sodium phosphate (DMP) and bovine serum albumin (BSA) as low and high molecular-weight bioactive molecule models, respectively, drug loading and in vitro release behaviours of chitosan-TPP nanofibres were investigated. The drug-loaded chitosan-TPP nanofibres showed a prolonged release profile with three distinct stages in physiological conditions because of the complicated release mechanisms involving diffusion of the drug and degradation of the nanofibre, and BSA-loaded nanofibres showed a smaller release rate than DMP-loaded nanofibres. It is proposed that biomimetic chitosan-based nanofibres may be of use in tissue engineering for sustained release of bioactive agents.

Objective: To find the enamel matrix proteins on the impact of enamel mineralization through experiments., Methods: A combination of protein and beneficial carboxyl groups was grafted on the surface of enamel defects of rats through UV radiation then put into the enamel matrix proteins of calcium phosphate agar acetate solution systems, through scanning enamel surface with the electron microscopy to observe the morphological changes of enamel then analyse the regulation that enamel matrix proteins have done to the white hydroxyapatite crystals on the composition and morphology., Results: In the enamel matrix protein added gel system, we can see the growth of hydroxyapatite crystals, and crystal showed a good degree of crystallinity and contained a small amount of CO3(2-) substituted hydroxyapatite crystals., Conclusion: The temperature at 37 degrees C water bath, after adding the enamel matrix proteins to gel system, the new hydroxyapatite crystals were numerous which proved that enamel matrix proteins played an important role in nucleation and growth of hydroxyapatite crystal, so it could be indicated that enamel matrix proteins could induce the enamel remineralization.

Objective: To study the influence of various active groups grafted on the enamel surface by means of self assembly on enamel biomineralization., Methods: The enamel was prepared by immersing the bicuspid tooth into 1 mmol/L ethanolic solution of a omega-functionalized (omega=PO4H2, SO3H, COOH or OH) group and deionized water solution of HSCH2CH2SO3Na for 24 h at room temperature. The contact angles and infrared (IR) images were used to identify the morphological changes of the enamel with chemisorption of the functional groups., Results: The contact angles and IR images showed that the omega-functionalized (omega=-PO4H2, -SO3H, -COOH, -OH or -CH3) group was chemisorbed on the enamel surface., Conclusion: Self assembled monolayers with omega-functionalized (omega=-PO4H2, -SO3H, -COOH, -OH or -CH3) group can be successfully formed on the enamel surface by hydrolyzation.

The reaction of H2S + S has been characterized at the multireference configuration interaction level with the geometries optimized using the aug-cc-pVTZ basis set and the single-point energy calculated using the aug-cc-pV(Q+d)Z basis set. As in the analogous reaction of H2 + S, the presence of an intersystem crossing enables products (SH + SH) to be formed on the singlet surface through S insertion, which bypasses the triplet barrier (19.1 kJ mol-1 relative to SH + SH) of the H abstraction route. This provides theoretical evidence for SH + SH formation without barrier beyond endothermicity at sufficiently low temperatures. The H abstraction route, however, is expected to be competitive at higher temperatures due to a much higher Arrhenius pre-exponential factor (6.9 x 10(14) cm3 mol-1 s-1 derived from TST calculation) than that of S insertion channel (3.7 x 10(13) cm3 mol-1 s-1, derived by a least-squares fit to the measurements). With a slightly higher transition-state barrier than that of the H abstraction channel, the production of S2 + H2 is less favored due to proceeding via intersystem crossing and insertion. While the formation of HSS + H is energetically unfavorable relative to SH + SH, recombination channels producing H2SS or the more stable HSSH are expected to occur under collisional stabilization conditions at high pressures.

A series of polymer/cholesteryl liquid crystal (LC) composite membranes were prepared. Polyurethane and polyvinyl chloride, as a substrate, were blended with cholesteryl tetraethylene glycol carbonate to form composite membranes in an electric field under normal conditions. The blood compatibility of composite materials was identified by the dynamic blood-clotting test, haemolysis ratio measurement, platelet adhesion and SEM observation. The results showed that the content of LC, the ordered extent of LC domains embedded in composite materials and the type of substrate have greater effects on the blood compatibility of polymer/LC composite materials. When the LC domains were properly oriented, polymer/LC composite membranes had an excellent haemocompatibility, fewer platelets were adhered and spread and showed little distortion on the surface of materials.

Poly(D,L-lactide) films were surface-modified by grafting collagen via NH(3) plasma to improve cell affinity. The modified films were characterized by IR analysis, contact angle measurement, SEM analysis and collagen quantity determination. It was demonstrated that -NH(2) and collagen were incorporated into the surface of PDLLA films. The hydrophilicity of the PDLLA film increased after NH(3) plasma treatment, but decreased with further collagen modification. More collagen was incorporated into the PDLLA films by a grating method as compared to that with an anchorage treatment. L929 fibroblast cells were used to evaluate the cell affinity of the modified films and control. It was shown that PDLLA films surface-modified by grafting collagen via NH(3) plasma more efficiently enhanced the cells attachment and proliferation than those films modified by collagen anchorage or only NH(3) plasma treatment.

The objective of this study was to synthesize new types of cholesteric liquid crystal compounds and study the anticoagulative properties of their composite membranes. Three kinds of cholesteric liquid crystal compounds were synthesized and characterized by infrared spectroscopy, differential scanning calorimetry and optical polarizing microscope. The polysiloxane, as a substrate, was blended with three liquid crystal compounds and was then used as membranes. The anticoagulative property of different polysiloxane liquid crystal composite membranes was identified by the blood compatibility tests. Three cholesteryl liquid crystals synthesized in this work contained hydrophilic soft chains and presented iridescent texture owned by cholesteric liquid crystals in the range of their liquid crystal state temperature, but only cholesteryl acryloyl oxytetraethylene glycol carbonate was in the liquid crystal state at body temperature. When liquid crystals were blended with polysiloxane to form polysiloxane/liquid crystal composite membranes, the haemocompatibility of these membranes could be improved to some extent. The blood compatibility of composite membranes whose hydrophilic property was the best was more excellent than that of other composite membranes, fewer platelets adhered and spread, and showed little distortion on the surface of materials.

The glass-ceramic mainly containing fluorophlogopite is one of widely used dental ceramics. In the K2O-CaO-MgO-Al2O3-SiO2-F system, a new-type glass-ceramic containing fluorophlogopite Ca-mica has been synthesized. Its crystalline was studied by XRD and EDS. The fluorophlogopite whose formula postulated K(1 - X )Ca( X/2)Mg(3)AlSi(3)O(10)F(2) was its main crystalline. The microstructure of the glass-ceramic displayed typical machinable microstructure with lath like crystals isolated and interlocking with different aspect ratio. The material also showed better bending strength (228.11 +/- 7.55 MPa). It took less than 12 minutes to fabricate a whole crown by dental CAD/CAM system with the glass-ceramic.

Background: Damaged articular cartilage has very limited capacity for spontaneous healing. Tissue engineering provides a new hope for functional cartilage repair. Creation of an appropriate cell carrier is one of the critical steps for successful tissue engineering. With the supposition that a biomimetic construct might promise to generate better effects, we developed a novel composite scaffold and investigated its potential for cartilage tissue engineering., Methods: Chitosan of 88% deacetylation was prepared via a modified base reaction procedure. A freeze-drying process was employed to fabricate a three-dimensional composite scaffold consisting of chitosan and type II collagen. The scaffold was treated with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide. Ultrastructure and tensile strength of the matrix were carried out to assess its physico-chemical properties. After subcutaneous implantation in rabbits, its in vivo biocompatibility and degradability of the scaffold were determined. Its capacity to sustain chondrocyte growth and biosynthesis was evaluated through cell-scaffold co-culture in vitro., Results: The fabricated composite matrix was porous and sponge-like with interconnected pores measuring from 100-250 microm in diameter. After cross-linking, the scaffold displayed enhanced tensile strength. Subcutaneous implantation results indicated the composite matrix was biocompatible and biodegradable. In intro cell-scaffold culture showed the scaffold sustained chondrocyte proliferation and differentiation, and maintained the spheric chondrocytic phenotype. As indicated by immunohistochemical staining, the chondrocytes synthesized type II collagen., Conclusions: Chitosan and type II collagen can be well blended and developed into a porous 3-D biomimetic matrix. Results of physico-chemical and biological tests suggest the composite matrix satisfies the constraints specified for a tissue-engineered construct and may be used as a chondrocyte carrier for cartilage tissue engineering.

Objective: To evaluate the biocompatibility of chitosan-g-polyvinylpyrrolidone as a new scaffold material., Methods: The material was tested and measured for water absorption and contact angle, followed by evaluation of the biocompatibility by implantation into rabbits and in vitro cultured with the corneal epithelial cells., Results: The water absorption rate of the material reached 1 100% with contact angle of 83-86. The results of implantation revealed partial degradation of the material 3 months after implantation, and much collagen and numerous corneal stromal cells appeared on the material without obvious inflammation reactions. In vitro coculture with epithelial cells showed good adhesion of the cells to the material which induced no obvious cytotoxicity., Conclusion: The novel chitosan derivative has excellent biocompatibility and can be used as a tissue scaffold material.

Objective: To prepare a scaffold material with good biocompatibility and biodegradability by compounding polylactic acid (PLA) and chitin., Methods: After preparation of PLA from lactic acid, the compounding of PLA and chitin was carried out by dissolving these 2 materials in one solution for reaction. The composite material was obtained and molded after the solvent was evaporized, and the safety tests of this resultant material were conducted in guinea pigs and New Zealand rabbits, respectively., Results: In allergic test, the guinea pigs responded to the digestion solution of the composite material in almost the same manner as to normal saline (the latter serving as negative control), and no obvious allergic reaction was observed in the animals except those in positive control group. Pyrogenic test by injecting the digestion solution of the composite material in 6 rabbits found a raise in the body temperature less than 0.2 degrees Celsius, with the total increase (adding up the individual temperature raise) less than 1.0 degrees Celsius, to meet the accepted criteria for the pyrogenic test. In subsequent toxicity test, the rabbits showed no signs of agitation or inanimate behavior after injection., Conclusions: PLA/chitin composite material conforms to the ISO10993-1, and can be used as a basic scaffold material in tissue engineering.

Objective: To prepare a tissue-engineered scaffold material using collagen as the matrices and to study the blood compatibility and tissue biocompatibility of this material., Methods: Physical, chemical and physical/chemical methods were used for the crosslinking of the collagen., Results: Dynamic blood clotting tests indicated that the blood clotting index (BCI) of the crosslinked collagen materials prepared by different means decreased as their contact with the blood was prolonged, and the collagen material obtained after crosslink through 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide method showed the highest BCI after contact with the blood within certain length of time. Hemolysis ratios of all the crosslinked collagen materials were shown to be much lower than 5%, well conforming to the requirement of biomaterials. Scanning electron microscopy showed that the platelets attached to the surface of the crosslinked collagen materials, having a fairly small number, were not morphologically distorted., Conclusion: The collagen materials obtained by the 3 crosslink methods have good blood compatibility. The cells grow well on the surfaces of the materials, indicating their good biocompatibility.

Karyotypes were analyzed using directing method for chorionic villi chromosome preparation in 52 specimens from spontaneous abortions. A paralleled cytogenetic study of 51 specimens from induced abortions was carried out. Among 52 specimens from spontaneous abortions, 11 (21%) were chromosomally abnormal and 82% of these were found to have autosomal trisomies (3,14,16,19,20 and 21). Trisomy 16 was the most common abnormality accounting for 44% of trisomic abortuses. A double trisomic abortus with a 48, XX, +16, +20 karyotype was detected. These results showed that chromosome abnormality is an important cause of spontaneous abortion. The relationship between chromosomal abnormalities of spontaneous abortuses and the factors relevant to the abnormalities are discussed.