Hypoxic preconditioning accelerates the healing of ischemic intestinal injury by activating HIF-1α/PPARα pathway-mediated fatty acid oxidation.

Hypoxic preconditioning (HPC) has been shown to improve organ tolerance to subsequent severe hypoxia or ischemia. However, its impact on intestinal ischemic injury has not been well studied. In this study, we evaluated the effects of HPC on intestinal ischemia in rats. Intestinal rehabilitation, levels of fatty acid oxidation (FAO) by-products, intestinal stem cells (ISCs), levels of hypoxia-inducible factor 1 subunit α (HIF-1α) and its downstream genes such as peroxisome proliferator-activated receptor α (PPARα), and carnitine palmitoyltransferase 1a (CPT1A) were assessed at distinct time intervals following intestinal ischemia with or without the interference of HIF-1α. Our data showed that HPC facilitates the restoration of the intestinal structure and enhances the FAO, by boosting intestinal stem cells. Additionally, HIF-1α, PPARα, and CPT1A mRNA and their protein levels were generally up-regulated in the small intestine of HPC rats as compared to the control group. Our vitro experiment also shows low-oxygen induces highly levels of HIF-1α and its downstream genes, with a concurrent increase in FAO products in IEC-6 cells. Furthermore, the above phenomenon could be reversed by silencing HIF-1α. In conclusion, we hypothesize that HPC can stimulate the activation of intestinal stem cells via HIF-1α/PPARα pathway-mediated FAO, thereby accelerating the healing process post ischemic intestinal injury.

GABPB1 plays a cancer-promoting role in non-small cell lung cancer.

BACKGROUND: GABPB1, the gene that encodes two isoforms of the beta subunit of GABP, has been identified as an oncogene in multiple malignant tumors. However, the role and mode of action of GABPB1 in malignant tumors, especially in lung cancer, are not well understood and need further research. METHODS: Our research focused on examining the biological function of GABPB1 in NSCLC (Non-Small Cell Lung Cancer). We analysed tumor data from public databases to assess the expression of GABPB1 in NSCLC  and its correlation with patient prognosis and investigated GABPB1 expression and methylation patterns in relation to the tumor microenvironment. In parallel, experiments were conducted using short hairpin RNA (shRNA) to suppress the GABPB1 gene in human lung cancer cells to evaluate the effects on cell proliferation, viability, and apoptosis. RESULTS: GABPB1 was widely expressed in various tissues of the human body. Compared to that in normal tissues, the expression of this gene was different in multiple tumor tissues. GABPB1 was highly expressed in lung cancer tissues and cell lines. Its expression was associated with molecular subtype and cellular signalling pathways, and a high level of GABPB1 expression was related to a poor prognosis in lung adenocarcinoma patients. The expression and methylation of GABPB1 affect the tumor microenvironment. After suppressing the expression of GABPB1 in both A549 and H1299 cells, we found a decrease in cell growth and expression, the formation of clones and an increase in the apoptosis rate. CONCLUSIONS: Our research verified that GABPB1 promotes the tumorigenesis of NSCLC and has an inhibitory effect on tumor immunity. The specific role of GABPB1 may vary among different pathological types of NSCLC. This molecule can serve as a prognostic indicator for lung adenocarcinoma, and its methylation may represent a potential breakthrough in treatment by altering the tumor immune microenvironment in lung squamous cell carcinoma. The role and mechanism of action of GABPB1 in NSCLC should be further explored.

Achyranthes bidentata polysaccharides improve cyclophosphamide-induced adverse reactions by regulating the balance of cytokines in helper T cells.

The manuscript aimed to study the immune function maintenance effect of Achyranthes bidentata polysaccharides (ABPs). The mice were divided into the control group, cyclophosphamide-induced (CTX) group, and ABPs-treated (ABP) group. The results showed that, compared with the CTX group, ABPs could significantly improve the spleen index and alleviate the pathological changes in immune organs. Ex vivo study of whole spleen cells, the levels of interleukin-2 (IL-2), interleukin-6 (IL-6), interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) were increased. The proliferation of lymphocytes and the proportion of CD3+CD4+ Th cells in peripheral blood mononuclear cells were increased. The transcription of GATA-3, Foxp3, and ROR γ t were decreased, while the transcription of T-bet was increased. The transcriptome sequencing analysis showed that the differentially expressed genes (DEGs) caused by ABPs-treated were mostly downregulated in CTX-induced mice. The Th2-related genes were significantly enriched in DEGs, with representative genes, including Il4, II13, Il9, etc., while increasing the expression of immune effector genes simultaneously, including Ccl3, Ccr5, and Il12rb2. It was suggested that ABPs possibly regulated the balance of cytokines in helper T cells to ameliorate the immune function of CTX-induced mice.

Looking for a Beam of Light to Heal Chronic Pain.

Chronic pain (CP) is a leading cause of disability and a potential factor that affects biological processes, family relationships, and self-esteem of patients. However, the need for treatment of CP is presently unmet. Current methods of pain management involve the use of drugs, but there are different degrees of concerning side effects. At present, the potential mechanisms underlying CP are not completely clear. As research progresses and novel therapeutic approaches are developed, the shortcomings of current pain treatment methods may be overcome. In this review, we discuss the retinal photoreceptors and brain regions associated with photoanalgesia, as well as the targets involved in photoanalgesia, shedding light on its potential underlying mechanisms. Our aim is to provide a foundation to understand the mechanisms underlying CP and develop light as a novel analgesic treatment has its biological regulation principle for CP. This approach may provide an opportunity to drive the field towards future translational, clinical studies and support pain drug development.

Superior energy storage properties in SrTiO3-based dielectric ceramics through all-scale hierarchical architecture.

The restricted energy density in dielectric ceramic capacitors is challenging for their integration with advanced electronic systems. Numerous strategies have been proposed to boost the energy density at different scales or combine those multiscale effects. Herein, guided by all-scale synergistic design, we fabricated Sr0.7Bi0.2TiO3 ceramics doped with (Bi0.5Na0.5)(Zr0.5Ti0.5)O3 by sintering the nanopowders by solution combustion synthesis, which demonstrate exceptional energy storage performance (ESP). Notably, an ultrahigh recoverable energy density of 11.33 J cm-3, accompanied by an impressive energy efficiency of 89.30%, was achieved at an extremely high critical electric field of 961 kV cm-1. These primary energy storage parameters outperform those of previously reported ceramic capacitors based on SrTiO3. Additionally, an excellent comprehensive performance is also realized, including a substantial power density of 156.21 MW cm-3 (at 300 kV cm-1), an extraordinarily short discharge time of 97 ns, a high Vickers hardness rating of approximately 8.23 GPa, and outstanding thermal and frequency stability. This enhancement can be attributed to the synergistic effect at all scales from atomic substitution, polar nano regions, submicrometer grain, and sample thickness. Consequently, this panoscopic approach has effectively demonstrated the potential to enhance the ESP of dielectric ceramics.

Gut Microbiome-Estrobolome Profile in Reproductive-Age Women with Endometriosis.

Microbiota is associated with our bodily functions and microenvironment. A healthy, balanced gut microbiome not only helps maintain mucosal integrity, prevents translocation of bacterial content, and contributes to immune status, but also associates with estrogen metabolism. Gut dysbiosis and estrobolome dysfunction have hence been linked to certain estrogen-dependent diseases, including endometriosis. While prior studies on microbiomes and endometriosis have shown conflicting results, most of the observed microbial differences are seen in the genital tract. This case-control study of reproductive-age women utilizes their fecal and urine samples for enzymatic, microbial, and metabolic studies to explore if patients with endometriosis have distinguishable gut microbiota or altered estrogen metabolism. While gut ß-glucuronidase activities, microbial diversity, and abundance did not vary significantly between patients with or without endometriosis, fecal samples of patients with endometriosis were more enriched by the Erysipelotrichia class and had higher folds of four estrogen/estrogen metabolites. Further studies are needed to elucidate what these results imply and whether there indeed is an association or causation between gut microbiota and endometriosis.

Overexpression of peanut (Arachis hypogaea L.) AhGRFi gene enhanced root growth inhibition under exogenous NAA treatment in Arabidopsis thaliana.

The 14-3-3 protein is a kind of evolutionary ubiquitous protein family highly conserved in eukaryotes. Initially, 14-3-3 proteins were reported in mammalian nervous tissues, but in the last decade, their role in various metabolic pathways in plants established the importance of 14-3-3 proteins. In the present study, a total of 22 14-3-3 genes, also called general regulatory factors (GRF), were identified in the peanut (Arachis hypogaea) genome, out of which 12 belonged to the ε group, whereas 10 of them belonged to the non- ε-group. Tissue-specific expression of identified 14-3-3 genes were studied using transcriptome analysis. The peanut AhGRFi gene was cloned and transformed into Arabidopsis thaliana. The investigation of subcellular localization indicated that AhGRFi is localized in the cytoplasm. Overexpression of the AhGRFi gene in transgenic Arabidopsis showed that under exogenous 1-naphthaleneacetic acid (NAA) treatment, root growth inhibition in transgenic plants was enhanced. Further analysis indicated that the expression of auxin-responsive genes IAA3, IAA7, IAA17, and SAUR-AC1 was upregulated and GH3.2 and GH3.3 were downregulated in transgenic plants, but the expression of GH3.2, GH3.3, and SAUR-AC1 showed opposite trends of change under NAA treatment. These results suggest that AhGRFi may be involved in auxin signaling during seedling root development. An in-depth study of the molecular mechanism of this process remains to be further explored.

Cytochemical and comparative transcriptome analyses elucidate the formation and ecological adaptation of three types of pollen coat in Zingiberaceae.

BACKGROUND: The pollen ornate surface of flowering plants has long fascinated and puzzled evolutionary biologists for their variety. Each pollen grain is contained within a pollen wall consisting of intine and exine, over which the lipoid pollen coat lies. The cytology and molecular biology of the development of the intine and exine components of the pollen wall are relatively well characterised. However, little is known about the pollen coat, which confers species specificity. We demonstrate three types of pollen coat in Zingiberaceae, a mucilage-like pollen coat and a gum-like pollen coat, along with a pollen coat more typical of angiosperms. The morphological differences between the three types of pollen coat and the related molecular mechanisms of their formation were studied using an integrative approach of cytology, RNA-seq and positive selection analysis. RESULTS: Contrary to the 'typical' pollen coat, in ginger species with a mucilage-like (Caulokaempferia coenobialis, Cco) or gum-like (Hornstedtia hainanensis, Hhn) pollen coat, anther locular fluid was still present at the bicellular pollen (BCP) stage of development. Nevertheless, there were marked differences between these species: there were much lower levels of anther locular fluid in Hhn at the BCP stage and it contained less polysaccharide, but more lipid, than the locular fluid of Cco. The set of specific highly-expressed (SHE) genes in Cco was enriched in the 'polysaccharide metabolic process' annotation term, while 'fatty acid degradation' and 'metabolism of terpenoids and polyketides' were significantly enriched in SHE-Hhn. CONCLUSIONS: Our cytological and comparative transcriptome analysis showed that different types of pollen coat depend on the residual amount and composition of anther locular fluid at the BCP stage. The genes involved in 'polysaccharide metabolism' and 'transport' in the development of a mucilage-like pollen coat and in 'lipid metabolism' and 'transport' in the development of a gum-like pollen coat probably evolved under positive selection in both cases. We suggest that the shift from a typical pollen coat to a gum-like or mucilage-like pollen coat in flowering plants is an adaptation to habitats with high humidity and scarcity of pollinators.

Carboxypeptidase E Regulates Activity-Dependent TrkB Neuronal Surface Insertion and Hippocampal Memory.

Activity-dependent insertion of the tropomyosin-related kinase B (TrkB) receptor into the plasma membrane can explain, in part, the preferential effect of brain-derived neurotrophic factor (BDNF) on active neurons and synapses; however, the underlying molecular mechanisms remain obscure. Here, we report a novel function for carboxypeptidase E (CPE) in controlling chemical long-term potentiation stimuli-induced TrkB surface delivery in hippocampal neurons. Total internal reflection fluorescence assays and line plot assays showed that CPE facilitates TrkB transport from dendritic shafts to the plasma membrane. The Box2 domain in the juxtamembrane region of TrkB and the C terminus of CPE are critical for the activity-dependent plasma membrane insertion of TrkB. Moreover, the transactivator of transcription TAT-CPE452-466, which could block the association between CPE and TrkB, significantly inhibited neuronal activity-enhanced BDNF signaling and dendritic spine morphologic plasticity in cultured hippocampal neurons. Microinfusion of TAT-CPE452-466 into the dorsal hippocampus of male C57BL/6 mice inhibited the endogenous interaction between TrkB and CPE and diminished fear-conditioning-induced TrkB phosphorylation, which might lead to an impairment in hippocampal memory acquisition and consolidation but not retrieval. These results suggest that CPE modulates activity-induced TrkB surface insertion and hippocampal-dependent memory and sheds light on our understanding of the role of CPE in TrkB-dependent synaptic plasticity and memory modulation.SIGNIFICANCE STATEMENT It is well known that BDNF acts preferentially on active neurons; however, the underlying molecular mechanism is not fully understood. In this study, we found that the cytoplasmic tail of CPE could interact with TrkB and facilitate the neuronal activity-dependent movement of TrkB vesicles to the plasma membrane. Blocking the association between CPE and TrkB decreased fear-conditioning-induced TrkB phosphorylation and led to hippocampal memory deficits. These findings provide novel insights into the role of CPE in TrkB intracellular trafficking as well as in mediating BDNF/TrkB function in synaptic plasticity and hippocampal memory.

Interleukin-1ß weakens paclitaxel sensitivity through regulating autophagy in the non-small cell lung cancer cell line A549.

Non-small cell lung cancer (NSCLC) poses a threat to human health and paclitaxel chemotherapy has been approved for the treatment of this type of cancer. However, resistance to treatment severely compromises the survival rate and prognosis of patients with NSCLC. The aim of the present study was to investigate the role of IL-1ß in paclitaxel sensitivity of NSCLC cells and elucidate the underlying mechanism. The expression of IL-1ß was found to be upregulated in NSCLC tissues and cells compared with healthy adjacent tissues and a normal epithelial cell line, respectively, as detected by reverse transcription-quantitative PCR and western blot analyses. Subsequently, Cell Counting Kit-8 assay and flow cytometry revealed that IL-1ß weakened the sensitivity of A549 cells to paclitaxel. It was subsequently demonstrated that IL-1ß induced A549 cell autophagy, while tunicamycin-induced autophagy increased the IL-1ß expression level and weakened paclitaxel sensitivity. Thus, the results revealed that IL-1ß reduced the sensitivity to paclitaxel in A549 cells by promoting autophagy and suggested that IL-1ß may be of value for improving the therapeutic efficacy of paclitaxel chemotherapy in NSCLC.

Coiled-coil domain-containing 68 promotes non-small cell lung cancer cell proliferation in vitro.

Coiled-coil domain-containing 68 (CCDC68) is a novel secretory protein that acts as a tumor suppressor gene in several types of malignant tumors. However, the role of CCDC68 in the development of lung cancer has not been extensively studied. In the present study, to explore the biological functions of CCDC68 in NSCLC, we performed cell proliferation, viability and apoptosis assays on human lung cancer cell lines upon CCDC68 gene silencing with short hairpin RNA. The results demonstrated that following knockdown of CCDC68 expression, cell proliferation was decreased and the apoptotic rates were increased in A549 and H1299 cells. The role and mechanism of CCDC68 in malignant tumors, particularly in lung cancer, should be further explored, and CCDC68 may serve as a novel target for treatment of lung cancer.

Ultrasound-guided bilateral pudendal nerve blocks of nulliparous women with epidural labour analgesia in the second stage of labour: a randomised, double-blind, controlled trial.

OBJECTIVE: To explore whether an ultrasound-guided pudendal nerve block (PNB) could decrease anaesthetic use, thereby shortening the length of the second stage of labour in women undergoing epidural analgesia. DESIGN: Prospective, single-centre, randomised, double-blind, controlled trial. SETTING: An obstetric centre in a general hospital in China. PARTICIPANTS: 72 nulliparous women were randomised, and 71 women completed the study. INTERVENTION: An ultrasound-guided bilateral PNB was administered to all study participants; the PNB group were given 0.25% ropivacaine 10 mL, while the control group were given 10 mL saline. MAIN OUTCOME MEASURE: The primary outcome measure was the duration of the second stage of labour. Secondary outcomes included additional bolus administration, total hourly bupivacaine consumption, difference in thickness between the contracted and relaxed rectus abdominis muscle before (DRAM1) and 30 min after (DRAM2) PNB, urge to defecate, maternal cooperation, preservation of the lower limb motor function, tightness of the perineum, and Numeric Rating Scale (NRS) score for pain. RESULTS: The duration of the second stage of labour was shorter in the PNB group than in the control group (difference of 33.8 min (95% CI 15.6 to 52.0), p<0.001). Additional bolus administration and total hourly bupivacaine consumption were lower in the PNB group than in the control group (p<0.001). DRAM2 was greater (p<0.001), rate of parturient women with the urge to defecate was higher (p=0.014), maternal cooperation was superior (p=0.002), and lower limb motor function preservation was greater (p=0.004) in the PNB group relative to the control group. Tightness of the perineum was eliminated from the results due to the inconsistent application of the criteria by the nursing staff. There was no significant difference in NRS scores between the groups. CONCLUSIONS: Nulliparous women with epidural analgesia who received an ultrasound-guided bilateral PNB may reduce their need for bupivacaine and consequently shorten the length of the second stage of labour, therein indicating that a bilateral PNB may serve as an additional effective adjunct method of labour analgesia. TRIAL REGISTRATION NUMBER: ChiCTR-IOR-16009121.

The Feasibility of All-Blastocyst-Culture and Single Blastocyst Transfer Strategy in Elderly Women: A Retrospective Analysis.

OBJECTIVE: To investigate the feasibility and clinical outcome of the all-blastocyst-culture and single blastocyst transfer strategy in women aged ≥35 years. METHODS: A retrospective analysis of patients aged ≥35 years undergoing IVF/ICSI was performed from January 2017 to April 2019 in the reproductive center of the Second Affiliated Hospital of Wenzhou Medical University. A total of 155 cases treated with ovarian hyperstimulation by prolonged protocol and implemented single (84 cases) or double (71 cases) blastocyst transfer were collected. Then, patients were further divided into <38 yr. group and ≥38 yr. group, and the laboratory and clinical outcomes were compared between the groups. RESULTS: The double-blastocyst-transfer (DBT) group showed higher clinical pregnancy rate and multiple pregnancy rate and lower neonatal birth weight than those in the single-blastocyst-transfer (SBT) group (P < 0.05). However, there were no statistically significant differences between the groups in the embryo implantation rate, biochemical pregnancy rate, miscarriage rate, preterm delivery rate, and term birth rate. For patients < 38 yr., SBT significantly reduced the multiple pregnancy rate and increased the neonate birth weight without significant reduction in the clinical pregnancy rate. While in the ≥38 yr. group, there are no differences in pregnancy outcomes between SBT and DBT. Logistic regression analysis showed that the number of MII oocytes was positively correlated with the live birth rate (OR = 1.18) and negatively correlated with the miscarriage rate (OR = 0.844), suggesting that elderly patients with relatively normal ovarian reserve would obtain better prospect in pregnancy. The number of fetal heart beat in pregnancy was negatively correlated with the live birth rate (OR = 0.322) and positively correlated with the preterm birth rate (OR = 7.16). CONCLUSION: The strategy of all-blastocyst-culture and single blastocyst transfer is feasible, safe, and effective for elderly patients with normal ovarian reserve, which would reduce the multiple pregnancy rate.

Hypoglycemic triterpenoid glycosides from Cyclocarya paliurus (Sweet Tea Tree).

Four new rarely occurred seco-dammarane triterpenoid glycosides (1-4) and four new dammarane triterpenoid glycosides (5-8), along with four known triterpenoids (9-12), were isolated from the 70% ethanol extract of the leaves of Cyclocarya paliurus (family Juglandaceae). Their structures were elucidated by extensive spectroscopic methods, including 1D/2D NMR and HRESIMS data, together with chemical analysis and DFT GIAO 13C NMR calculation. In bioassay, compounds 5-8 significantly increased glucose consumption in 3T3-L1 adipocytes, which could be the bioactive constituents for the anti-diabetes effect of the traditional usage of C. paliurus.

Fabrication, Investigation, and Application of Light-Responsive Self-Assembled Nanoparticles.

Light-responsive materials have attracted increasing interest in recent years on account of their adjustable on-off properties upon specific light. In consideration of reversible isomerization transition for azobenzene (AZO), it was designed as a light-responsive domain for nanoparticles in this research. At the same time, the interaction between AZO domain and ß-cyclodextrin (ß-CD) domain was designed as a driving force to assemble nanoparticles, which was fabricated by two polymers containing AZO domain and ß-CD domain, respectively. The formed nanoparticles were confirmed by Dynamic Light Scattering (DLS) results and Transmission Electron Microscope (TEM) images. An obvious two-phase structure was formed in which the outer layer of nanoparticles was composed of PCD polymer, as verified by 1HNMR spectroscopy. The efficient and effective light response of the nanoparticles, including quick responsive time, controllable and gradual recovered process and good fatigue resistance, was confirmed by UV-Vis spectroscopy. The size of the nanoparticle could be adjusted by polymer ratio and light irradiation, which was ascribed to its light-response property. Nanoparticles had irreversibly pH dependent characteristics. In order to explore its application as a nanocarrier, drug loading and in vitro release profile in different environment were investigated through control of stimuli including light or pH value. Folic acid (FA), as a kind of target fluorescent molecule with specific protein-binding property, was functionalized onto nanoparticles for precise delivery for anticancer drugs. Preliminary in vitro cell culture results confirmed efficient and effective curative effect for the nanocarrier on MCF-7 cells.

Genome-wide association and differential expression analysis of salt tolerance in Gossypium hirsutum L at the germination stage.

BACKGROUND: Salinity is a major abiotic stress seriously hindering crop yield. Development and utilization of tolerant varieties is the most economical way to address soil salinity. Upland cotton is a major fiber crop and pioneer plant on saline soil and thus its genetic architecture underlying salt tolerance should be extensively explored. RESULTS: In this study, genome-wide association analysis and RNA sequencing were employed to detect salt-tolerant qualitative-trait loci (QTLs) and candidate genes in 196 upland cotton genotypes at the germination stage. Using comprehensive evaluation values of salt tolerance in four environments, we identified 33 significant single-nucleotide polymorphisms (SNPs), including 17 and 7 SNPs under at least two and four environments, respectively. The 17 stable SNPs were located within or near 98 candidate genes in 13 QTLs, including 35 genes that were functionally annotated to be involved in salt stress responses. RNA-seq analysis indicated that among the 98 candidate genes, 13 were stably differentially expressed. Furthermore, 12 of the 13 candidate genes were verified by qRT-PCR. RNA-seq analysis detected 6640, 3878, and 6462 differentially expressed genes at three sampling time points, of which 869 were shared. CONCLUSIONS: These results, including the elite cotton accessions with accurate salt tolerance evaluation, the significant SNP markers, the candidate genes, and the salt-tolerant pathways, could improve our understanding of the molecular regulatory mechanisms under salt stress tolerance and genetic manipulation for cotton improvement.

Statistical Modelling Outcome of In Vitro Fertilization and Intracytoplasmic Sperm Injection: A Single Centre Study.

BACKGROUND: Assisted reproductive techniques (ART) have been extensively used to treat infertility. Inaccurate prediction of a couple's fertility often leads to lowered self-esteem for patients seeking ART treatment and causes fertility distress. OBJECTIVE: This prospective study aimed to statistically analyze patient data from a single reproductive medical center over a period of 18 months, and to establish mathematical models that might facilitate accurate prediction of successful pregnancy when ART are used. METHODS: In the present study, we analyzed clinical data prospectively collected from 760 infertile patients visiting the second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University between June 1, 2016 and December 31, 2017. Various advanced statistical methods, including broken-line regression, were employed to analyze the data. RESULTS: Age remained the most important factor affecting the outcome of IVF/ICSI. Using the broken-line regression model, the fastest clinical pregnancy declining age was between 25 and 32. Female infertility type was found to be a key predictor for the number of good-quality embryos and successful pregnancy, along with the antral follicle count (AFC), total number of embryos, recombinant follicle stimulating hormones (rFSH) dosage, estradiol (E2) on the trigger day, and total number of oocytes retrieved. rFSH dosage was also significantly associated with the number of oocytes retrieved and the number of frozen embryos. CONCLUSION: The fastest clinical pregnancy declining age is ranged between 25 and 32, and female infertility type is evidenced as another key predictive factor for the cumulative outcome of ART.

Modifying the mechanical properties of gold nanorods by copper doping and triggering their cytotoxicity with ultrasonic wave.

We proposed the use of copper (Cu) doping to modify the mechanical properties of gold nanorods (AuNRs) and demonstrated the triggering of the cytotoxicity of Cu-doped AuNRs with ultrasonic wave. The mechanical properties of Cu-doped AuNRs were analyzed theoretically by using the density-function calculation and it was found that Cu-Au bond is much weaker than Au-Au bond. In experiments, AuNRs without and with Cu doping were synthesized and they were found to be low cytotoxic to both human liver hepatocellular carcinoma (HepG2) cells and normal liver cells (L02). It was found that Cu-doped AuNRs can be broken into small gold nanoparticles (<5 nm) under high-power ultrasonic wave while undoped AuNRs were quite stable, although the amount of Cu doped into AuNRs was quite small (0.2%). The small gold nanoparticles are found to be with high toxicity to HepG2 cells. The cellular viability of the HepG2 cells dropped to nearly zero after being incubated with Cu-doped AuNRs (50 nM), which had been treated with a 300-W ultrasonic wave. Our findings suggest a novel method for modifying the mechanical properties of AuNRs and especially for triggering their cytotoxicity which is quite useful for in vitro therapy of cancer cells.

Layer-by-layer hyaluronic acid-chitosan coating promoted new collagen ingrowth into a poly(ethylene terephthalate) artificial ligament in a rabbit medical collateral ligament (MCL) reconstruction model.

The ideal artificial ligament graft should have favorable biocompatibility to facilitate cell adhesion, proliferation, and collagen regeneration. In this present study, surface modification was performed on a poly(ethylene terephthalate) (PET) artificial ligament graft by layer-by-layer (LBL) self-assembly coating of hyaluronic acid (HA) and chitosan (CS). The surface characterization of the ligament was examined using scanning electron microscopy, atomic force microscopy, and energy-dispersive X-ray spectroscopy. The results of in vitro culturing of human foreskin fibroblast cells supported the hypothesis that the LBL coating of CS-HA could promote the cell proliferation and adhesion on the sheets. A rabbit medical collateral ligament reconstruction model was used to evaluate the effect of this LBL coating in vivo. The final results proved that this LBL coating could significantly promote and enhance new collagen formation among the graft fibers. On the basis of these results, we conclude that such CS-HA assembly coating could enhance PET graft biocompatibility in vitro and in vivo, and a CS-HA-coated PET graft has considerable potential as a desirable substitute for ligament reconstruction.

The use of layer by layer self-assembled coatings of hyaluronic acid and cationized gelatin to improve the biocompatibility of poly(ethylene terephthalate) artificial ligaments for reconstruction of the anterior cruciate ligament.

In this study layer by layer (LBL) self-assembled coatings of hyaluronic acid (HA) and cationized gelatin (CG) were used to modify polyethylene terephthalate (PET) artificial ligament grafts. Changes in the surface properties were characterized by scanning electron microscopy, attenuated total reflection Fourier transform infrared spectroscopy, energy-dispersive X-ray spectroscopy, and contact angle and biomechanical measurements. The cell compatibility of this HA-CG coating was investigated in vitro on PET films seeded with human foreskin dermal fibroblasts over 7days. The results of our in vitro studies demonstrated that the HA-CG coating significantly enhanced cell adhesion, facilitated cell growth, and suppressed the expression of inflammation-related genes relative to a pure PET graft. Furthermore, rabbit and porcine anterior cruciate ligament reconstruction models were used to evaluate the effect of this LBL coating in vivo. The animal experiment results proved that this LBL coating significantly inhibited inflammatory cell infiltration and promoted new ligament tissue regeneration among the graft fibers. In addition, the formation of type I collagen in the HA-CG coating group was much higher than in the control group. Based on these results we conclude that PET grafts coated with HA-CG have considerable potential as substitutes for ligament reconstruction.