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.

Improved mammalian family phylogeny using gap-rare multiple sequence alignment: A timetree of extant placentals and marsupials.

The timing of mammalian diversification in relation to the Cretaceous-Paleogene (KPg) mass extinction continues to be a subject of substantial debate. Previous studies have either focused on limited taxonomic samples with available whole-genome data or relied on short sequence alignments coupled with extensive species samples. In the present study, we improved an existing dataset from the landmark study of Meredith et al. (2011) by filling in missing fragments and further generated another dataset containing 120 taxa and 98 exonic markers. Using these two datasets, we then constructed phylogenies for extant mammalian families, providing improved resolution of many conflicting relationships. Moreover, the timetrees generated, which were calibrated using appropriate molecular clock models and multiple fossil records, indicated that the interordinal diversification of placental mammals initiated before the Late Cretaceous period. Additionally, intraordinal diversification of both extant placental and marsupial lineages accelerated after the KPg boundary, supporting the hypothesis that the availability of numerous vacant ecological niches subsequent to the mass extinction event facilitated rapid diversification. Thus, our results support a scenario of placental radiation characterized by both basal cladogenesis and active interordinal divergences spanning from the Late Cretaceous into the Paleogene.

Nucleic Acid Amplification by Template-Dominated Click Chemistry for Ultrasensitive DNA/RNA Detection on an Electrochemical Readout Platform.

As an enzyme-free exponential nucleic acid amplification method, the click chemistry-mediated ligation chain reaction (ccLCR) has shown great prospects in the molecular diagnosis. However, the current optics-based ccLCR is challenged by remarkable nonspecific amplification, severely hindering its future application. This study demonstrated that the severe nonspecific amplification was generated probably due to high random collision in the high DNA probe concentration (µM level). To solve this hurdle, a nucleic acid template-dominated ccLCR was constructed using nM-level DNA probes and read on an electrochemical platform (cc-eLCR). Under the optimal conditions, the proposed cc-eLCR detected a low-level nucleic acid target (1 fM) with a single-base resolution. Furthermore, this assay was applied to detect the target of interest in cell extracts with a satisfactory result. The proposed cc-eLCR offers huge possibility for click chemistry-mediated enzyme-free exponential nucleic acid amplification in the application of medical diagnosis and biomedical research.

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.

A Rare Case of Hb H Disease and Systemic Lupus Erythematosus.

Anemia is common in patients with systemic lupus erythematosus (SLE). The association between thalassemia and SLE is rare. In this study, we report the first patient who was found to have a severe hemolytic anemia caused by combination of SLE and Hb H disease. The patient had a more severe presentation in the hematological system. Our case indicates that for a patient who was diagnosed with SLE and developed deterioration in her hematological cell lines, investigation of other possible coexisting causes would be warranted.

Effectiveness of High Tibial Osteotomy with or without Other Procedures for Medial Compartment Osteoarthritis of Knee: An Update Meta-Analysis.

To improve the long-term outcomes of high tibial osteotomy (HTO) for gonarthritis, many cartilage repair procedures appeared, but their effects were controversial. To evaluate the efficacy of cartilage repair procedures during HTO for gonarthritis, we performed this update meta-analysis. We performed the system retrieval for clinical trials using various databases and then pooled the outcomes of the included studies. Fifteen studies were involved. The pooled results indicated that there were no significant differences in Kellgren and Lawrence (KL) scale (mean difference [MD] = 0.02, 95% confidence interval [CI] = -0.01 to 0.06, p = 0.24), the femorotibial angle (MD = 0.06, 95% CI = -0.04 to 0.16, p = 0.22), and magnetic resonance imaging (MRI) outcomes (MD = 12.53, 95% CI = -2.26 to 27.32, p = 0.10) of patients in experimental group than control. The subgroup analysis showed that the clinical outcomes of abrasion arthroplasty (AA) were worse than control group (standardized mean difference [SMD] -2.65, 95% CI = -3.67 to -1.63, p < 0.001), while mesenchymal stem cells (MSCs) injection improved the clinical outcomes (SMD = 2.37, 95% CI = 1.25-3.50, p < 0.001). There were significant differences between the two groups in arthroscopic (SMD = 1.38, 95% CI = 0.82-1.94, p < 0.001) and histologic results (relative risk [RR] = 1.77, 95% CI = 1.36-2.29, p < 0.001). The pain relief (MD = 0.17, 95% CI = -3.26 to 3.61, p = 0.92) and operative complications (RR = 1.42, 95% CI = 0.83-2.42; p = 0.19) of the two groups had no significant differences. Our analysis supports that concurrent cartilage repair procedures might improve arthroscopic and histologic outcomes, but they have no beneficial effect on clinical outcomes, radiograph, MRI, and pain relief. The concurrent procedures do not increase the risk of operative complication. Furthermore, MSC has some beneficial effects on clinical outcomes, while AA might play an opposite role.

Configurationally Stable Platinahelicene Enantiomers for Efficient Circularly Polarized Phosphorescent Organic Light-Emitting Diodes.

Chiral materials with circularly polarized luminescence (CPL) are potentially applicable for 3D displays. In this study, by decorating the pyridinyl-helicene ligands with -CF3 and -F groups, the platinahelicene enantiomers featured superior configurational stability, as well as high sublimation yield (>90 %) and clear CPPL properties, with dissymmetry factors (|gPL |) of approximately 3.7×10-3 in solution and about 4.1×10-3 in doped film. The evaporated circularly polarized phosphorescent organic light-emitting diodes (CP-PhOLEDs) with two enantiomers as emitters exhibited symmetric CPEL signals with |gEL | of (1.1-1.6)×10-3 and decent device performances, achieving a maximum brightness of 11 590 cd m-2 , a maximum external quantum efficiency up to 18.81 %, which are the highest values among the reported devices based on chiral phosphorescent PtII complexes. To suppress the effect of reverse CPEL signal from the cathode reflection, the further implementation of semitransparent aluminum/silver cathode successfully boosts up the |gEL | by over three times to 5.1×10-3 .

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.

Prenatal diagnosis of hemivertebrae--A likely association with 7q deletion.

OBJECTIVE: This study aims to investigate the possible cause of a prenatal case of hemivertebrae with a 7q terminal deletion. CASE REPORT: This case describes a fetus with hemivertebrae in thoracic vertebrae as the sole antenatal sonographic finding. Genetic testing was performed in order to find more information after the abnormal ultrasound finding. The array-based comparative genomic hybridization results showed that the fetus had approximately 6.4 Mb deletion of 7q36. We discussed the two genes (SHH and HLXB9) that may be associated with hemivertebrae in the deletion region and reviewed several literatures about 7q36 deletion. CONCLUSION: Our results suggest that the phenotype of hemivertebra in our case may be related to the deletion of 7q36.

Genetic Evaluation of Copy Number Variations, Loss of Heterozygosity, and Single-Nucleotide Variant Levels in Human Embryonic Stem Cells With or Without Skewed X Chromosome Inactivation.

Human embryonic stem cells (hESCs) exhibiting skewed X chromosome inactivation (XCI) have been reported. The copy number variations (CNVs), loss of heterozygosity (LOH), or single-nucleotide variant (SNV) events in those epigenetically distinct cells remain unknown, and whether such genetic abnormalities will influence the XCI status of hESCs is unclear. In this study, three hESCs with skewed XCI, three with random XCI, and two male hESC lines at different passages were analyzed for CNVs and LOH levels using a high-resolution genotyping microarray. Whole-exome sequencing was used to investigate the potentially damaging SNVs. On average, 17.6 CNVs and 5.3 cases of LOH were identified in the skewed hESCs, which were similar to the rates observed in random hESCs. Five recurrent CNV regions were uniquely identified in the skewed hESCs, but all of them were considered polymorphisms. With the exception of a nongenic CNV, no additional CNVs were detected on the X chromosome in the skewed hESCs. Although the XCI status in two hESC lines was observed to be changed from random to skewed, no significant CNV difference was identified before and after the XCI change. SNV analysis indicated that normal alleles are maintained for most genes within copy-neutral LOH regions. Three types of expression patterns were observed in heterozygous alleles, and the damaging SNVs in skewed hESCs favored the expression of the wild-type alleles. In conclusion, in the present study, we did not find genetic differences in the CNV and LOH levels between hESCs with and without skewed XCI. Wild-type allele expression in the presence of damaging SNVs on the X chromosome in skewed hESCs might alleviate adverse effects in those hESCs.

[Analysis of de novo copy number variations in a family affected with autism spectrum disorders using high-resolution array-based comparative genomic hybridization].

OBJECTIVE: To analyze de novo copy number variations (CNVs) in a Chinese family affected with autism spectrum disorders (ASD). METHODS: Affymetrix Cytogenetics Whole Genome 2.7M Array assay was performed to identify potential CNVs in four members from the family. RESULTS: A total of 89 de novo CNV regions were identified in the autistic siblings. The CNV regions in total have exceeded 1/1000 of the lengths of chromosomes 5, 11 and 14. In addition, de novo CNV regions were also identified at 3p26.1, 4q22.2, and 5p15.2, which encompassed 10 genes associated with nerve development including GRM7, GRID2 and CTNND2. CONCLUSION: A number of nerve development associated genes were at the de novo CNV sites, which may provide new clues for genetic research of ASD. High-resolution array-comparative genomic hybridization is an effective method for detecting submicroscopic chromosomal imbalances.

Degradation of pyridine by one Rhodococcus strain in the presence of chromium (VI) or phenol.

A Rhodococcus strain, Chr-9, which has the ability to degrade pyridine and phenol and reduce chromium (VI) (Cr (VI)) was isolated. The strain could grow with pyridine as the sole carbon and nitrogen source, and its pyridine-degradation capability was enhanced by 100 mg l(-1) phenol; however, the degradation of pyridine was inhibited when the phenol concentration was greater than 400 mg l(-1). The hydroxylation of pyridine suggested that the stimulation and inhibition of phenol to the pyridine degradation may be attributed to competition of phenol and pyridine for the hydroxylase gene. Strain Chr-9 was also able to reduce Cr (VI) when glucose and LB was used as the carbon source; however, the Cr (VI) reduction did not occur when pyridine was the sole carbon and energy source. In addition, strain Chr-9 could reduce Cr (VI) and simultaneously degrade pyridine in the presence of glucose. To the best of our knowledge, strain Chr-9 is the first Rhodococcus strain reported to degrade pyridine in the presence of Cr (VI), and the first strain with the pyridine degradation being stimulated by low concentrations of phenol.

Effect of mini-tyrosyl-tRNA synthetase/mini-tryptophanyl-tRNA synthetase on ischemic angiogenesis in rats: proliferation and migration of endothelial cells.

The purpose of this study was to determine the mechanism of mini-tyrosyl-tRNA synthetase/mini-tryptophanyl-tRNA synthetase (mini-TyrRS/mini-TrpRS) on ischemic angiogenesis in rats with acute myocardial infarction and proliferation, migration, potential signaling pathways of rat coronary venular endothelial cells (RCVECs). The effects of mini-TyrRS/mini-TrpRS on RCVECs proliferation were evaluated using the MTT colorimetric assay. Cell migration was assayed using a modified Boyden chamber technique. The potential involvement of Erk and PI3K signaling pathways was explored using selective chemical inhibitor or Western-blot analysis. Left coronary artery ligation was used to establish the model of acute myocardial infarction in rats (Sprague-Dawley male rats, 200-250 g, 2-3 months old), 20 µl of mini-TyrRS, mini-TrpRS, or PBS (vehicle) was injected subcutaneously every 12 h. The rats were randomly divided into four experimental groups: sham operated group; coronary artery ligation (CAL); CAL + mini-TyrRS (20 µl, twice daily, 600 µg kg(-1) day(-1)); and CAL + mini-TrpRS (20 µl, twice daily, 600 µg kg(-1) day(-1)). The experiment was carried out at four time points on the 3rd, 7th, 14th, and 28th day after ligation. To determine whether mini-TyrRS/mini-TrpRS affected the angiogenesis activity of rats with myocardial infarction, we measured the myocardial infarction size by TTC staining, and microvessel density (MVD) was determined by CD34 staining. The results show that proliferation and migration in RCVECs could be promoted by mini-TyrRS at concentrations of 1-100 µg/ml, and inhibited by mini-TrpRS. Phospho-PI3-kinase and Erk expression increased significantly when mini-TyrRS was added, but could be attenuated by mini-TrpRS. Compared to the CAL group, the myocardial infarction size of the mini-TyrRS group at the 3rd, 7th, 14th, and 28th day were decreased, while mini-TrpRS increased, but only in days 14 and 28 was there a significant difference. Except that, the microvessel density of RCVECs was promoted in mini-TyrRS group but inhibited in the mini-TrpRS group. These results indicated that angiogenesis could be either stimulated by mini-TyrRS or inhibited by mini-TrpRS.

Different angiogenesis effect of mini-TyrRS/mini-TrpRS by systemic administration of modified siRNAs in rats with acute myocardial infarction.

We aimed to clarify the different angiogenesis effects of mini-tyrosyl-tRNA synthetase (TyrRS)/minitryptophanyl-tRNA synthetase (TrpRS) in rodent primates with acute myocardial infarction, by delivering small interfering RNAs (siRNAs) systemically in a liposomal formulation. Left coronary artery ligation was used to establish the model of acute myocardial infarction in rats; mini-TyrRS/mini-TrpRS-specific siRNAs were encapsulated in stable nucleic acid lipid particles (SNALP), and administered by intravenous injection to rats. Rats were divided into four experiment groups: sham operated group (no left anterior descending artery [LAD] occlusion); negative control group (LAD occlusion + saline injection); mock transfection group (LAD occlusion + mock transfected injection); experiment group (LAD occlusion + mini-TyrRS/mini-TrpRS-specific siRNAs injection). Silencing efficiency was assayed by Western blotting. To determine whether mini-TyrRS/mini-TrpRS affected the angiogenesis activity of rats with myocardial infarction, we measured the myocardial infarction size by TTC staining, and the capillary density using immunohistochemistry staining, to investigate the expression of factor VIII. The myocardial infarction size and the capillary density of mini-TyrRS-siRNA group were respectively 18.89% and 8.64/0.1 mm(2) 1 month after ligation, while in the mini-TrpRS-siRNA group these values were 7.33% and 17.32/0.1 mm(2), significantly different compared with the mock transfection group (14.19%; 13.56/0.1 mm(2)) and negative control group (14.28%; 13.89/0.1 mm(2)), P < 0.05. There were no significant changes between the mock transfection group and the negative control group, P > 0.05. These results indicated that angiogenesis is either stimulated by mini-TyrRS or inhibited by mini-TrpRS in rat models with acute myocardial infarction.

Rupture of splenic artery aneurysm in pregnancy: a review of the literature and report of two cases.

BACKGROUND: Splenic artery aneurysms are an uncommon form of vascular disease, which have a significant potential for rupture, most commonly associated with pregnancy, typically presents as sudden, unexpected death. As a consequence, the initial recognition and diagnosis of splenic artery aneurysm rupture take place only at autopsy. CLINICAL CASES: This report presents 2 cases of sudden death resulting from splenic artery aneurysm in a pregnant woman and a postpartum woman, respectively. The former splenic artery aneurysm were measuring 1 cm in diameter and the latter splenic artery aneurysm 5.5 x 5 x 2 cm in size. Histologic examination of the both vessels wall showed severe morphologic changes of degeneration together with an attenuation of arterial internal elastica. CONCLUSIONS: To our knowledge, splenic artery aneurysm in pregnant woman is unusual vital disease. It is essential that obstetricians are alert to the prodromal and catastrophic symptoms of splenic artery aneurysm. Early recognition and prompt management, including early resected electively, are vital to the survival of both mother and fetus.

[The biomechanical study and clinical application of monosegmental pedicle instrumentation by endplate method in the fracture vertebrae for thoracolumbar fracture].

OBJECTIVE: To evaluate the biomechanical and clinical effect of the treatment of thoracolumbar fracture with monosegmental pedicle instrumentation in the fracture vertebrae by endplate method. METHODS: Twenty-four porcine thoracolumbal spinal model, divided into four groups randomly, compared the stability of these four groups through pull-out testing. Retrospective study of 49 patients with thoracolumbar fracture who were treated with this technique, to observe the fusion of bone graft, the height of the anterior and posterior range, the angle of kyphosis and the volume of spinal canal, the loss of rectification, low back pain, and the limitation of activity of lumbar. RESULTS: The endplate method group is more stability than the parallel method group, and the pedicle screw in the fracture vertebrae can get enough stability. After operation all 49 cases achieved satisfactory reduction, strong bone fusion, no reduction loss, no refractoriness low back pain, limitation of motion of lumbar et al. CONCLUSION: Monosegmental pedicle instrumentation by endplate method in the fracture vertebrae for thoracolumbar fracture can get enough extraction stability, and get satisfied clinical effect.

[Estradiol promote myocardial angiogenesis in a rat model of acute myocardial infarction through estrogen receptors].

OBJECTIVE: To study the influence of estradiol on myocardial angiogenesis and the expression of estrogen receptors in a rat model of myocardial infarction. METHODS: Acute myocardial infaction (AMI) model was established by ligation of left anterior descending coronary in ovariectomized SD rats, which then were treated with different doses of estradiol Benzoate. Estradiol concentration in serum was measured by Radioimmunoassay before AMI and 4 weeks later, microvascular density in myocardium was evaluated with detection of expression of VIII factor by Immunohistochemistry, and estrogen receptor alpha and beta protein in the myocardium were detected with Western blot at 28 d after AMI. RESULTS: Estradiol levels in serum significantly degraded after ovariectomized, but increased after the treatment of different doses of estradiol. Microvascular density in myocardium 4 weeks after AMI in ovariectomized group was obviously lower than that of acute myocardial infarction group and estrogen therapy groups. Estrogen replacement therapy group had the highest microvascular density. The expression of estrogen receptor alpha and beta protein in the myocardium showed significant different, which was the highest in estrogen replacement therapy group and the lowest in ovariectomized group. CONCLUSION: Estrogen improves myocardial angiogenesis in rats after AMI, this effect may be related to the expression of estrogen receptor a and beta in myocardium.

Primary lymphoblastic B-cell lymphoma of the stomach: a case report.

Primary stomach lymphoblastic B-cell lymphoma (B-LBL) is a rare tumor. We describe a primary stomach B-LBL in a 38 years old female who presented with nonspecific complaints of fatigue and vomiting for 2 mo. Gastrofiberscopy revealed a large gastric ulcer, which was successfully resected. Pathology showed a lymphoblastic cell lymphoma arising from the stomach, and there was no evidence of disease at any extrastomach site. Immunohistochemical staining and gene rearrangement studies supported that the stomach tumor was a clonal B-cell lymphoma. Therefore, the diagnosis of B-LBL was made based on the stomach specimen.

Regional expression of the hypoxia-inducible factor (HIF) system and association with cardiomyocyte cell cycle re-entry after myocardial infarction in rats.

Hypoxia-inducible factor (HIF)-1alpha and-2alpha have diverse actions on the myocardium, but the importance of direct effects on cardiac myocytes is unclear. To define their regional accumulation and association with cardiomyocyte cell cycle change after myocardial infarction (MI), a rat MI model was established by occluding the coronary arteries. To further prove a causative relationship between HIF and cell cycle regulation, cultured cardiomyocytes were transfected with adenoviral vectors carrying HIF-1alpha and HIF-2alpha. Two weeks after MI, both HIF-1alpha and HIF-2alpha mRNA were moderately increased in the infarcted left ventricle and noninfarcted left ventricle; HIF-2alpha amplification was also detected in areas of the interventricular septum and the right ventricle. In concordance with the changes in mRNA levels, immunohistochemistry signals of HIF-1alpha and HIF-2alpha were characterized by different regional distributions. In the myocardium adjacent to the infarcted tissue, a significant correlation between HIF-1alpha or HIF-2alpha and Ki-67 labeling index was observed (P < 0.001). Immunohistochemical double staining showed that HIF positive cardiomyocytes underwent DNA synthesis. Cardiomyocytes treated with HIF-1alpha or -2alpha expressed Ki-67, phosphohistone H3, and bromodeoxyuridine effectively in vitro. In conclusion, HIF-1alpha and HIF-2alpha had a distinct spatial expression pattern in a rat model of ischemic heart disease. Both HIF subunits might be potent stimuli for cardiomyocytes to re-enter the cell cycle and initiate DNA synthesis.