A nature-inspired multifunctional adhesive for cartilage tissue-biomaterial integration.

Surgical adhesives play a crucial role in tissue integration and repair, yet their application in wet conditions has been severely limited by inadequate adhesive strength and subpar biocompatibility. Furthermore, tissue adhesives have rarely been reported in cartilage tissue repair. In this study, a three-armed dopamine-modified hyaluronic acid derivative adhesive was prepared to function as a bio-inspired adhesive in moist environments. To meet the clinical requirements for cartilage tissue adhesion, we studied its chemical structure, including microscopic morphology, adhesion properties with materials and tissues, in vivo degradation rules, and biological evaluation. The OGMHA8-DOPA adhesive with the optimal aldehyde substitution degree and dopamine-grafting rate was determined by analyzing the experimental conditions. SEM results revealed that the cartilage tissue adhered to a porous interconnected structure. The excellent biocompatibility of the material not only facilitated chondrocyte adhesion but also supported their proliferation on its surface. Animal experiments have demonstrated that this material has no observable inflammatory response or incidence of fibrous capsule formation. The degradation timeline of the material extends beyond the duration of two weeks. The dopamine-modified adhesive exhibited a tight interfacial binding force between the biomaterial and cartilage tissue and excellent biocompatibility in watery tissue, revealing its potential for application in cartilage tissue repair and minimally invasive surgery.

Purification, identification and characterization of an esterase with high enantioselectivity to (S)-ethyl indoline-2-carboxylate.

OBJECTIVE: To purify an esterase which can selectively hydrolyze (R,S)-ethyl indoline-2-carboxylate to produce (S)-indoline-2-carboxylic acid and characterize its enzymatic properties. RESULTS: An intracellular esterase from Bacillus aryabhattai B8W22 was isolated and the purified protein was identified as a carboxylesterase by MALDI-TOF mass spectrometry. The enzyme (named BaCE) was 59.03-fold purification determined to be of approximately 35 kDa. Its specific activity was 0.574 U/mL with 20% yield. The enzyme showed maximum activity at pH 8.5 and 30 °C and was stable at 20-30 °C using pNPB as the substrate. The Km, Vmax, kcat and kcat/Km of the esterase were 0.52 mM, 6.39 µM/min, 26.87 min-1 and 51.67 mM/min, respectively. The esterase demonstrated high enantioselectivity toward (S)-ethyl indoline-2-carboxylate with 96.55% e.e.p at 44.39% conversion, corresponding to an E value of 133.45. CONCLUSIONS: In this study, a new esterase BaCE with an apparent molecular mass of 35 kDa was purified to homogeneity for the first time. The esterase from Bacillus aryabhattai B8W22 was isolated with a purification more than 59-fold and a yield of 20% by anion exchange chromatography and hydrophobic interaction chromatography. And its biochemical characterization were described in detail with pNPB as substrate. It displayed high enantioselectivity toward (S)-ethyl indoline-2-carboxylate. We next plan to highly express esterase BaCE in Escherichia coli, and apply it to industrial production of (S)-indoline-2-carboxylic acid.

A peptide nanofibrous indicator for eye-detectable cancer cell identification.

A unique peptide nanofibrous indicator (NFI) is fabricated by mixing a borono-peptide with alizarin red S, followed by subsequent binding and self-assembly. The NFI thus obtained exhibits an intense response to sialyl Lewis X tetrasaccharide, which is overexpressed in human hepatocellular carcinoma cell lines. Importantly, this NFI has the capability of specifically recognizing human hepatocellular liver carcinoma (HepG2) cells through the eye-detectable color change resulting from strong binding-induced displacement. This novel technique for cancer cell identification through direct unaided eye judgment will open up an innovative platform for cancer cell detection.

Interferon regulatory factor-7 is required for hair cell development during zebrafish embryogenesis.

Interferon regulatory factor-7 (IRF7) is an essential regulator of both innate and adaptive immunity. It is also expressed in the otic vesicle of zebrafish embryos. However, any role for irf7 in hair cell development was uncharacterized. Does it work as a potential deaf gene to regulate hair cell development? We used whole-mount in situ hybridization (WISH) assay and morpholino-mediated gene knockdown method to investigate the role of irf7 in the development of otic vesicle hair cells during zebrafish embryogenesis. We performed RNA sequencing to gain a detailed insight into the molecules/genes which are altered upon downregulation of irf7. Compared to the wild-type siblings, knockdown of irf7 resulted in severe developmental retardation in zebrafish embryos as well as loss of neuromasts and damage to hair cells at an early stage (within 3 days post fertilization). Coinjection of zebrafish irf7 mRNA could partially rescued the defects of the morphants. atp1b2b mRNA injection can also partially rescue the phenotype induced by irf7 gene deficiency. Loss of hair cells in irf7-morphants does not result from cell apoptosis. Gene expression profiles show that, compared to wild-type, knockdown of irf7 can lead to 2053 and 2678 genes being upregulated and downregulated, respectively. Among them, 18 genes were annotated to hair cell (HC) development or posterior lateral line (PLL) development. All results suggest that irf7 plays an essential role in hair cell development in zebrafish, indicating that irf7 may be a member of deafness gene family.

Validation of the G.LAB MD41A0 upper arm blood pressure monitor in patients with diabetes mellitus according to the AAMI/ESH/ISO 81060-2:2018 Universal Standard.

OBJECTIVE: The objective of this study is to determine the accuracy of the G.LAB MD41A0 upper-arm oscillometric blood pressure (BP) monitor for self/home BP measurement in patients with diabetes according to the Association for the Advancement of Medical Instrumentation /European Society of Hypertension /International Organization for Standardization (AAMI/ESH/ISO) Universal Standard (ISO 81060-2:2018). METHODS: Patients with diabetes were recruited according to AAMI/ESH/ISO Universal Standard using the same arm sequential BP measurement method. The standard cuff of the test device was used for arm circumference 22-44 cm. RESULTS: A total of 92 patients with diabetes were recruited and 85 were analyzed with an average age of 55.1 ± 17.7 years, 48 men, and arm circumference of 32.0 ± 6.0 cm. For the validation Criterion 1, the mean ± SD of the differences between the test device and reference BP readings was 0.89 ± 6.04/-0.84 ± 5.11 mmHg (systolic/diastolic). For Criterion 2, the SD of the averaged BP differences between the test device and reference BP per subject was 4.23/4.19 mmHg (systolic/diastolic). CONCLUSION: The G.LAB MD41A0 upper arm BP monitor fulfilled all the requirements of the AAMI/ESH/ISO Universal Standard (ISO 81060-2:2018) in patients with diabetes and can be recommended for self/home use.

Facile construction of nanofibers as a functional template for surface boron coordination reaction.

A facile strategy to perform the boron coordination reaction on a template of nanofibers is developed. Peptides with phenylboronic acid tails (peptidyl boronic acids) are designed and prepared as building blocks that can self-assemble into nanofibers. After the addition of vicinal diol structural motifs to the self-assembling system, matrix-assisted laser desorption-ionization time-of-flight mass spectrometry indicates that the boron coordination reaction occurs on the template of nanofibers, which results in the increase of the width and roughness of the nanofibers as demonstrated by transmission electron microscopy and atomic force microscopy measurements. Because the surface-bound vicinal diol structural motifs have an ability to form hydrogen bonds with the peptide segments on the nanofibers, which restrain and disturb the hydrogen-bonding interaction among the nanofibers, the network structure formed based on the entanglement of nanofibers via hydrogen-bonding interaction is destroyed, which leads to a gel-sol transition. The novel concept of post-self-assembly modification demonstrated here could lead to a new technique for using self-assembled nanostructures in the emerging fields of nanoscience and nanotechnology.

Supramolecular architectures self-assembled from asymmetrical hetero cyclopeptides.

In this study, two asymmetrical cyclopeptides (CP1 and CP2) were designed and synthesized. The self-assembly behaviors of the asymmetrical cyclopeptides at varying pHs were investigated in terms of transmission electron microscopy (TEM), circular dichroism (CD), and Fourier transform infrared (FT-IR) spectroscopy. It was found that the self-assembly of CP1 resulted in the formation of nanofibers with α-helix conformation, while CP2 self-assembled into well-ordered nanorods with anti-parallel ß-sheet conformation. The strategy demonstrated here presents great potential for preparation of well-defined nanostructures via rationally designing the molecular structures of cyclopeptides.

A preliminary anatomical study on the association of condylar and occlusal asymmetry.

The aim of this study was to test the hypothesis that condylar and occlusion asymmetry are not associated. For each of 22 skulls, the asymmetry of condyles was graded by one examiner and the asymmetry of occlusion by another examiner, both blinded to each other's evaluation, as 0 = symmetrical, 1 = mild asymmetrical and 2 = severe asymmetrical. There were 18 condyles graded the same as to their occlusion, but in four, the grades differed by one degree. Nine were graded symmetrical, seven were mild, and six were graded severely asymmetrical condyles. The corresponding figures for occlusion were: 10 were graded symmetrical, seven were graded mildly asymmetrical, and five were graded severely asymmetrical occlusion. The relation between occlusion and condylar asymmetry was tested using Goodman-Kruskal's gamma and was found to be 0.970 (p < 0.001). The null hypothesis was not supported. The results indicate that asymmetry of occlusion and condyles are associated, which indicates the need for further studies on larger samples, and in vivo studies.

Silk fibroin/chitosan/TGF-ß1-loaded microsphere scaffolds for cartilage reparation.

BACKGROUND: Transforming growth factor-ß1 (TGF-ß1) plays an important role in chondrocyte growth and the synthesis of extracellular matrix (ECM). Due to the rapid metabolism, controlled release systems for TGF-ß1 have attracted increasing interest recently. OBJECTIVE: In this study, a silk fibroin (SF)/chitosan (CS) scaffold incorporated with TGF-ß1-loaded microspheres (MSs) was created for cartilage reparation. METHOD: The optimal proportion of the SF/CS composite scaffold was determined by evaluating their micromorphology and the proliferation rate of fibroblasts on the surface. Then, SF/CS/TGF-ß1-loaded MS scaffolds were prepared by the adsorption method. TGF-ß1 release capacity, degradation patterns, cytocompatibility and in vivo implantation were evaluted. RESULTS: The SF/CS/TGF-ß1-loaded MS scaffold showed good TGF-ß1 release over more than 16 days, which could sequentially stimulate chondrocyte synthetic activity. In vitro cell proliferation experiments showed the SF/CS/TGF-ß1-loaded MS scaffold could promote chondrocytes adhesion, growth, proliferation and maintained the cellular morphology. An in vivo study demonstrated that a low inflammatory response was observed in rats and that the materials exhibited good biocompatibility. CONCLUSION: the results indicated that our SF/CS/TGF-ß1-loaded MS scaffold constitute a promising therapeutic option for cartilage reparation.

Proangiogenic Peptide Nanofiber Hydrogels for Wound Healing.

Rapid vascularization is vital for dermal regeneration, nutrient and nutrition transfer, metabolic waste removal, and prevention of infection. This study reports on a series of proangiogenic peptides designed to undergo self-assembly and promote angiogenesis and hence skin regeneration. The proangiogenic peptides comprised an angiogenic peptide segment, GEETEVTVEGLEPG, and a ß-sheet structural peptide sequence. These peptides dissolved easily in ultrapure water and rapidly self-assembled into hydrogels in a pH-dependent manner, creating three-dimensional fibril network structures and nanofibers as revealed by a scanning microscope and a transmission electron microscope. In vitro experiments showed that the peptide hydrogels favored adhesion and proliferation of mouse fibroblasts (L929) and human umbilical vein endothelial cells (HUVECs). In particular, many connected tubes were formed in the HUVECs after 8 h of culture on the peptide hydrogels. In vivo experiments demonstrated that new blood vessels grew into the proangiogenic peptide hydrogels within 2 weeks after subcutaneous implantation in mice. Moreover, the proangiogenic-combined hydrogels exhibited faster repair cycles and better healing of skin defects. Collectively, the results indicate that the proangiogenic peptide hydrogels are a promising therapeutic option for skin regeneration.

Nanofibers Self-assembled from Structural Complementary Borono-decapeptides.

A series of structural complementary decapeptides with phenyl boronic acid tails or borono-decapeptides (BPs) were designed and synthesized for supramolecular self-assembly. After dissolving these borono-decapeptides in deionized (DI) water, well-defined nanofibers were formed in BP1 (B(OH)(2) VEKELVKEKL-OH) and BP3 (B(OH)(2) AELELARARL-OH). It was found that the self-assembled borono-decapeptide BP1 and BP3 have a parallel ß-sheet conformation in the formed nanofibers. The strategy demonstrated here shows a great prospect in preparation of well-ordered nanofibers via rationally designing the molecular structures of peptides.

The response of Pyropia haitanensis to inorganic arsenic under laboratory culture.

Up to now, complicated organoarsenicals were mainly identified in marine organisms, suggesting that these organisms play a critical role in arsenic biogeochemical cycling because of low phosphate and relatively high arsenic concentration in the marine environment. However, the response of marine macroalgae to inorganic arsenic remains unknown. In this study, Pyropia haitanensis were exposed to arsenate [As(V)] (0.1, 1, 10, 100 µM) or arsenite [As(III)] (0.1, 1, 10 µM) under laboratory conditions for 3 d. The species of water-soluble arsenic, the total concentration of lipid-soluble and cell residue arsenic of the algae cells was analyzed. As(V) was mainly transformed into oxo-arsenosugar-phosphate, with other arsenic compounds such as monomethylated, As(III), demethylated arsenic and oxo-arsenosugar-glycerol being likely the intermediates of arsenosugar synthesis. When high concentration of As(III) was toxic to P. haitanensis, As(III) entered into the cells and was transformed into less toxic organoarsenicals and As(V). Transcriptome results showed genes involved in DNA replication, mismatch repair, base excision repair, and nucleotide excision repair were up-regulated in the algae cells exposed to 10 µM As(V), and multiple genes involved in glutathione metabolism and photosynthetic were up-regulated by 1 µM As(III). A large number of ABC transporters were down-regulated by As(V) while ten genes related to ABC transporters were up-regulated by As(III), indicating that ABC transporters were involved in transporting As(III) to vacuoles in algae cells. These results indicated that P. haitanensis detoxifies inorganic arsenic via transforming them into organoarsenicals and enhancing the isolation of highly toxic As(III) in vacuoles.

Dual targeting of a thermosensitive nanogel conjugated with transferrin and RGD-containing peptide for effective cell uptake and drug release.

In this paper, both arginine-glycine-aspartic acid (RGD)-containing peptide and transferrin (Tf) were conjugated to the thermosensitive poly(N-isopropylacrylamide-co-propyl acrylic acid) (poly(NIPAAm-co-PAAc)) nanogel to prepare a dual-targeting drug carrier. The obtained nanogel was characterized in terms of fluorescence spectroscopy, UV-vis spectroscopy, dynamic light scattering (DLS) and transmission electron microscopy (TEM). In order to track the dual-ligand conjugated nanogel, fluorescein isothiocyanate (FITC) was further conjugated to the nanogel. A cell internalization experiment showed that the dual-ligand conjugated nanogel exhibited obviously enhanced endocytosis by HeLa cells as compared with non-tumorous cells (COS-7 cells). The drug-loaded dual-ligand conjugated nanogel could be transported efficiently into the target tumor cells and the anti-tumor effect was enhanced significantly, suggesting that the dual-ligand conjugated nanogel has great potential as a tumor targeting drug carrier.

Spatial analysis of tuberculosis cases in migrants and permanent residents, Beijing, 2000-2006.

To determine the role of the migrant population in the transmission of tuberculosis (TB), we investigated the distribution and magnitude of TB in permanent residents and migrant populations of Beijing, People's Republic of China, from 2000 through 2006. An exploratory spatial data analysis was applied to detect the "hot spots" of TB among the 2 populations. Results, using the data obtained from 2004-2006, showed that people who migrated from the western, middle, and eastern zones of China had a significantly higher risk of having TB than did permanent residents. These findings indicate that population fluctuations have affected the rate of TB prevalence in Beijing, and interventions to control TB should include the migrant population.

Three-Dimensionally Printed Silk-Sericin-Based Hydrogel Scaffold: A Promising Visualized Dressing Material for Real-Time Monitoring of Wounds.

A wound dressing which can be convenient for real-time monitoring of wounds is particularly attractive and user-friendly. In this study, a nature-originated silk-sericin-based (SS-based) transparent hydrogel scaffold was prepared and evaluated for the visualization of wound care. The scaffold was fabricated from a hybrid interpenetrating-network (IPN) hydrogel composed of SS and methacrylic-anhydride-modified gelatin (GelMA) by 3D printing. The scaffold transformed into a highly transparent hydrogel upon swelling in PBS, and thus, anything underneath could be easily read. The scaffold had a high degree of swelling and presented a regularly macroporous structure with pores around 400 µm × 400 µm, which can help maintain the moist and apinoid environment for wound healing. Meanwhile, the scaffolds were conducive to adhesion and proliferation of L929 cells. A coculture of HaCaT and HSF cells on the scaffold showed centralized proliferation of the two cells in distributed layers, respectively, denoting a promising comfortable environment for re-epithelialization. Moreover, in vivo studies demonstrated that the scaffold showed no excessive inflammatory reaction. In short, this work presented an SS-based transparent hydrogel scaffold with steerable physical properties and excellent biocompatibility through 3D printing, pioneering promising applications in the visualization of wound care and drug delivery.

Effect of a New Annular Incision on Biomechanical Properties of the Intervertebral Disc.

OBJECTIVE: To compare the biomechanical properties of a novel annular incision technique, an oblique incision made approximately 60° to the spinal column, with the traditional transverse and longitudinal annular slit incision in an ex vivo sheep lumbar spine model. METHODS: Sixteen sheep lumbar spines were used for the current ex vivo biomechanical comparative study. Functional spine unit (FSU) specimens composed of two vertebrae and one disc in the middle was cut from the whole lumbar spine. Annular slit incisions of 5 mm were made in different directions with a 15-blade knife at the intervertebral disc, following which partial discectomy was performed to produce the following groups: control with no incision, transverse slit, longitudinal slit and oblique slit groups. The specimens were then subjected to flexion-extension, lateral bending, axial rotation and compression tests. RESULTS: As expected, the control group showed the least range of motion (ROM) in the flexion-extension test. The oblique slit group showed a trend toward a smaller ROM than the transverse and longitudinal groups in 1, 2, 3 and 5 Nm flexion-extension tests; these differences were not statistically significant (P > 0.05). In addition, the transverse (5.80° ± 0.20°), longitudinal (5.77° ± 0.67°) and oblique (5.47° ± 0.43°) slit groups showed a significantly larger ROM than the control group (3.22° ± 0.28°) in 2 Nm lateral bending tests (P < 0.05). Compared with the transverse and longitudinal groups, the oblique group also showed a trend toward a smaller ROM in lateral bending tests (P > 0.05). Following increments in the axial torsion force, the ROM was greater in all four experimental groups than the ROM with 1 Nm axial torsion. Furthermore, a significantly smaller axial rotational ROM was found in the oblique than the transverse group for 1 and 5 Nm force (P < 0.05). With increase in the axial force to 5 Nm, the ROM in the oblique slit group (4.71° ± 0.52°) was significantly smaller than that in the transverse group (7.25° ± 0.46°, P < 0.05), but not significantly different from that of the longitudinal slit group (5.84° ± 0.23°, P > 0.05). Comparable ultimate loads to failure were found in the oblique, transverse and longitudinal groups; the highest ultimate load to failure being in the control group (P > 0.05). CONCLUSION: The novel oblique slit annular incision to the intervertebral disc showed a trend toward better biomechanical properties than the traditional transverse and longitudinal slit incisions.

[Effect of shengmai injection on TRAIL death receptor of patients with congestive heart failure].

OBJECTIVE: To explore the levels of DR4 and DR5, the death receptor of soluble tumor necrosis factor-related apoptosis inducing ligand (TRAIL) in the patients with congestive heart failure (CHF) and the effect of shengmai injection (SI) on them. METHODS: Sixty-four CHF patients were randomized into two groups, the SI group treated by SI and the control group treated with conventional treatment. Another 30 healthy persons were enrolled as the healthy control group. The serum levels of sDR4 and sDR5 were determined by sandwich ELISA before and after treatment. RESULTS: The serum levels of sDR4 and sDR5 were obviously higher in CHF patients than in the healthy control subjects (P < 0.01), showing a rising trend with the aggravation of the degree of cardiac function impairment. Levels of sDR4 and sDR5 were lowered in the two treated groups after treatment, with better effects gotten in the SI group. CONCLUSION: Close relationship presents between cardiac function status and levels of DR4 and DR5 in patients with CHF. DR4 and DR5 might play an important role in the occurrence and progression of myocardial cell apoptosis in patients with CHF, and SI may acts vitally to slow down the progress of CHF and improve patients' heart function by decreasing the levels of sDR4 and sDR5.

Malignant triton tumor of the cervical spine: report of one case and review of the literature.

Malignant triton tumor (MTT) is a highly aggressive malignant neoplasm, classified as a variant of malignant peripheral nerve sheath tumor with rhabdomyoblastic differentiation. MTT is rarely reported in children, and its true prevalence may be underestimated. We herein report such a case in an 8-year-old boy who presented with a mass over the trapezius muscle. He was previously diagnosed with neurofibromatosis in the same area. Four years later, a follow-up magnetic resonance imaging revealed an intradural tumor recurrence at the level of C1-C7. An immunohistochemical test result was positive for S-100 protein and desmin, which confirmed the diagnosis. The patient outcome was fatal despite multimodal therapy. The possibility of this rare but devastating tumor must always be considered when patients present with new compressive spinal symptoms.

A coumarin derivative as a fluorogenic glycoproteomic probe for biological imaging.

Fluorescence imaging in living cells is typically carried out using a functionalized fluorescent dye. But it often causes strong background noise under many conditions where washing is not applicable. Here, we report on a coumarin based fluorogenic probe, which can be used as a bioorthogonal-labeling tool for glycoproteins. The results indicated that the probe was able to image glycoproteins in living cells and it may also be suitable for intracellular imaging.

Photo-switched self-assembly of a gemini α-helical peptide into supramolecular architectures.

An azobenzene-linked symmetrical gemini α-helical peptide was designed and prepared to realize the light-switched self-assembly. With the reversible molecular structure transition between Z- and U-structures, the morphology of the self-assembled gemini α-helical peptide can reversibly change between nanofibers and nanospheres in acidic medium, and between nanospheres and vesicles in basic medium.