Iron accumulation induced by hepcidin1 knockout accelerates the progression of aging osteoporosis.

OBJECTIVE: Iron accumulation is associated with osteoporosis. This study aims to explore the effect of chronic iron accumulation induced by hepcidin1 deficiency on aging osteoporosis. METHODS: Iron accumulation in hepcidin1 knockout aging mice was assessed by atomic absorption spectroscopy and Perl's staining. Bone microarchitecture was observed using Micro-CT. Hepcidin, ferritin, oxidative stress, and markers of bone turnover in serum were detected by enzyme-linked immunosorbent assay. Bone formation and resorption markers were measured by real-time quantitative PCR. Cell aging was induced by D-galactose treatment. CCK-8, flow cytometry, EdU assays, and Alizarin red staining were performed to reveal the role of hepcidin1 knockout in cell model. Iron Colorimetric Assay Kit and western blot were applied to detect iron and ferritin levels in cells, respectively. RESULTS: In hepcidin1-knockout mice, the ferritin and iron contents in liver and tibia were significantly increased. Iron accumulation induced by hepcidin1 knockout caused a phenotype of low bone mass and deteriorated bone microarchitecture. Osteogenic marker was decreased and osteoclast marker was increased in mice, accompanied by increased oxidative stress level. The mRNA expression levels of osteoclast differentiation markers (RANKL, Mmp9, OPG, Trap, and CTSK) were up-regulated, while bone formation markers (OCN, ALP, Runx2, SP7, and Col-1) were down-regulated in model group, compared to wild type mice. In vitro, hepcidin1 knockdown inhibited proliferation and osteogenic differentiation, while promoted apoptosis, with increased levels of iron and ferritin. CONCLUSION: Iron accumulation induced by hepcidin1 deficiency aggravates the progression of aging osteoporosis via inhibiting osteogenesis and promoting osteoclast genesis.

Inducing Circularly Polarized Luminescence by Confined Synthesis of Ultrasmall Chiral Carbon Nanodot Arrays in Pyrene-Based MOF Thin Film.

Combining the features of the host-guest system and chirality is an efficient strategy to achieve circularly polarized luminescence (CPL). Herein, well-defined chiral carbon nanodot (chirCND) arrays were confined-synthesized by low-temperature calcination of a chiral amino acid loaded metal-organic framework (MOF) to induce high CPL. An achiral porous pyrene-based MOF NU-1000 thin film as the host template was prepared by a liquid-phase epitaxial layer-by-layer fashion, and chiral amino acids as the carbon sources could be confined in the porous MOF and carbonized to homogeneous and ultrasmall chirCND arrays, resulting in a chirCNDs@NU-1000 thin film (l-CNDsx@NU-1000; x = l-cysteine (cys), l-serine, l-histidine, l-glutamic acid, and l-pyroglutamic acid). The results show the pristine chirCNDs by directly carbonizing chiral amino acids hardly endow them with a CPL property. By contrast, benefiting from the arrayed confinement and coordination interaction between chirCNDs and NU-1000, the chirality transfer on the excited state of chirCNDs@NU-1000 is enabled, leading to strong CPL performance (a high luminescence dissymmetry factor glum of l-CNDscys@NU-1000 thin film reached 1.74 × 10-2). This study of chirCNDs encapsulated in fluorescent MOF thin films provides a strategy for developing uniform chiral carbon nanoarrays and offers chiral host-guest thin-film materials for optical applications.

Blapstin, a Diapause-Specific Peptide-Like Peptide from the Chinese Medicinal Beetle Blaps rhynchopetera, Has Antifungal Function.

Drug resistance against bacteria and fungi has become common in recent years, and it is urgent to discover novel antimicrobial peptides to manage this problem. Many antimicrobial peptides from insects have been reported to have antifungal activity and are candidate molecules in the treatment of human diseases. In the present study, we characterized an antifungal peptide named blapstin that was isolated from the Chinese medicinal beetle Blaps rhynchopetera used in folk medicine. The complete coding sequence was cloned from the cDNA library prepared from the midgut of B. rhynchopetera. It is a 41-amino-acid diapause-specific peptide (DSP)-like peptide stabilized by three disulfide bridges and shows antifungal activity against Candida albicans and Trichophyton rubrum with MICs of 7 µM and 5.3 µM, respectively. The C. albicans and T. rubrum treated with blapstin showed irregular and shrunken cell membranes. In addition, blapstin inhibited the activity of C. albicans biofilm and showed little hemolytic or toxic activity on human cells and it is highly expressed in the fat body, followed by the hemolymph, midgut, muscle, and defensive glands. These results indicate that blapstin may help insects fight against fungi and showed a potential application in the development of antifungal reagents. IMPORTANCE Candida albicans is one of the conditional pathogenic fungi causing severe nosocomial infections. Trichophyton rubrum and other skin fungi are the main pathogens of superficial cutaneous fungal diseases, especially in children and the elderly. At present, antibiotics such as amphotericin B, ketoconazole, and fluconazole are the main drugs for the clinical treatment of C. albicans and T. rubrum infections. However, these drugs have certain acute toxicity. Long-term use can increase kidney damage and other side effects. Therefore, obtaining broad-spectrum antifungal drugs with high efficiency and low toxicity for the treatment of C. albicans and T. rubrum infections is a top priority. Blapstin is an antifungal peptide which shows activity against C. albicans and T. rubrum. The discovery of blapstin provides a novel clue for our understanding of the innate immunity of Blaps rhynchopetera and provides a template for designing antifungal drugs.

Iron Porphyrin as a Cytochrome P450 Model for the Degradation of Dye.

Organic dyes are widely used in the textile, biological, medical and other fields. However, a serious environmental problem has appeared because of the presence of organic dyes in industrial aqueous effluents. Thus, the efficient treatment of organic dyes in industrial wastewaters is currently in real demand. The current study investigated the oxidative degradation of the organic dye gentian violet by meso-tetra(carboxyphenyl) porphyriniron(III), [FeIII(TCPP)] as a cytochrome P450 model and iodosylbenzene (PhIO) as an oxidant at room temperature. The degradation reaction was monitored by UV-vis absorption spectroscopy via the observation of UV-vis spectral changes of the gentian violet. The results showed that the efficiency of catalyzed degradation reached more than 90% in 1 h, indicating the remarkable oxidative degradation capacity of the [FeIII(TCPP)]/PhIO system, which provided an efficient approach for the treatment of dyeing wastewater.

Whole-Genome Sequencing Identified KCNJ12 and SLC25A5 Mutations in Port-Wine Stains.

Port-wine stains (PWSs) are a congenital capillary malformed disorder and are caused by a number of somatic mutations that disrupt vascular development. However, the underlying genetic mutations in the pathogenesis of PWS have not yet been fully elucidated. To understand PWS genetic variations and investigate novel genetic mutations, we extracted genomic DNA from four sporadic PWS patients and then performed whole-genome sequencing (WGS). Using Sorting Intolerant from Tolerant (SIFT), PolyPhen2, Mutation Assessor, MetaSVM to identify candidate genetic mutations and whole-exome sequencing (WES) to confirm the identified variants. We found a previously reported G protein subunit alpha q (GNAQ) mutation c.548G > A, p.Arg183Gln in one case, whereas no such mutation was found in the other three samples. Moreover, six novel somatic mutations in three genes, including KCNJ12, SLC25A5, POTEE, were found in these four samples. Importantly, WES also verified the KCNJ12 (c.433G > A, p.Gly145Ser) and SLC25A5 (c.413G > A, p.Arg138His) mutations in other five sporadic PWS patients, with the frequency of 60% (3 of 5) and 40% (2 of 5), respectively. Thus, we reveal in this study two novel somatic mutations, KCNJ12 and SLC25A5, in the sporadic PWS patients for the first time. These findings highlight the genetic polymorphism of PWS and provide potential clinical prediction targets for this disease.

Anionic Porous Zn-Metalated Porphyrin Metal-Organic Framework with PtS Topology for Gas-Phase Photocatalytic CO2 Reduction.

Presented here are the synthesis and gas-phase photocatalytic CO2 reduction of an anionic porous Zn-metalated porphyrin metal-organic framework (MOF) induced by an ionic liquid. The desired CO2 affinity and deep conduction band position of the MOF catalyst provide strong kinetic and thermodynamic advantages for photocatalytic CO2 to CH4 conversion with high selectivity (∼70%) in H2O vapor.

In Situ Synthesis of Surface-Mounted Novel Nickel(II) Trimer-Based MOF on Nickel Oxide Hydroxide Heterostructures for Enhanced Methanol Electro-Oxidation.

Engineering the heterogeneous interface fusing MOFs and inorganic active component is an effective strategy to improve the electrochemical performance. Herein, we report a new Ni3-based MOF (denoted as CTGU-24) with an infrequent two-fold interpenetrating 3D (3,8)-connected network constructed from Ni(II) trimer and mixed tripodal tectonics for the electrocatalytic methanol oxidation reaction (MOR). In order to improve its stability and activities, the heterogeneous hybrid CTGU-24@NiOOH has been fabricated successfully via the first preparation of the NiOOH nanosphere and then in situ formation of CTGU-24 decorated on the NiOOH surface. Moreover, the integration of CTGU-24@NiOOH and different additives [acetylene black (AB) and ketjen black (KB)], resulting in the optimized hybrid sample AB&CTGU-24@NiOOH (4:4). It attains better MOR performance with an area-specific peak current density of 34.53 mA·cm-2 than pure CTGU-24 (14.99 mA·cm-2) and improved durability in an alkali medium. The new findings indicate that the CTGU-24@NiOOH heterostructure formed in situ and the integration of moderate additives are critical to optimizing and improving electrocatalytic activity of pure MOF crystalline material.

[Clinical observation of different surgical methods for metaphyseal sequelae of ulna].

OBJECTIVE: To investigate the effect and safety of ulnar osteochondroma resection, ulnar minimally invasive osteotomy, external fixation and ulnar lengthening in the treatment of forearm deformity of metaphyseal extension of ulna. METHODS: From August 2005 to December 2013, there were 20 cases of ulnar metaphyseal sequelae, including 15 males and 5 females, aged from 7 to 13(10.00±2.34) years, the course of disease ranged for 6 to 11(8.10±1.52) months. The clinical manifestations were shortening of the affected forearm and bending to the ulnar side. The postoperative evaluation included pain, activities of daily living, orthopedic effect and the range of motion of wrist, elbow and forearm. The radiological evaluation included ulnar length, radial joint inclination angle and wrist epiphysis growth. RESULTS: All patients healed without infection. The only operation related to complications was ulnar lengthening, including 1 case of nonunion, 2 cases of ulnar lengthening callus fracture and 1 case of temporary radial nerve palsy. All patients were followed up for 4 to 7.5 years, with an average of (6.03±1.33) years. There were statistically significant differences in changes of wrist radial deviation, ulnar deviation, forearm pronation and supination in all cases (P<0.05). Radiological evaluation parameters (ulnar variance, radial joint angle, wrist slip) were improved, and the differences were statistically significant(P<0.05). The modified Green and O'Brien wrist function scores at the last follow-up were significantly different from those before operation (P<0.05). The clinical effect of wrist joint was significantly different from that before operation (P<0.05). The Mayo elbow function scoreat the latest follow-up was significantly different from that before operation (P<0.05). The clinical effect of elbow joint was significantly different from that before operation (P<0.05). CONCLUSION: Ulnar lengthening is not beneficial to prevent the development of long-term deformity. Simple resection of osteochondroma of distal ulna is beneficial to prevent the development of deformity. Patients with limited rotation of wrist joint and forearm and strong demand for improvement of appearance can be actively treated.

Common Strategy: Mounting the Rod-like Ni-Based MOF on Hydrangea-Shaped Nickel Hydroxide for Superior Electrocatalytic Methanol Oxidation Reaction.

Developing efficient metal-organic framework (MOF)-based electrocatalysts with improvable activity and persistence toward the methanol oxidation reaction (MOR) is attracting great research attention but still remains an enormous challenge. Herein, a facile strategy, hydrangea-shaped nickel hydroxide template-directed synthesis of the hierarchically structured Ni-MOF on the Ni(OH)2 heterocomposite (denoted as Ni-Ni) for efficient MOR, is developed. The unique hierarchical structure and synergistic effect of the heterocomposite afford more exposed active sites, a facile ion diffusion path, and improved conductivity, favorable for improving MOR catalytic performance. Remarkably, the optimized Ni-Ni-2 material delivers an excellent activity with a high peak current density (24.6 mA cm-2). Furthermore, to prove the universality of this strategy, NixCu1-x(OH)2 isometallic hydroxide was used as the precursor, and a series of MOF-74/CuxNi1-x(OH)2 (denoted as Ni-NiCu) heterogeneous materials have been prepared and could be used as an effective electrocatalyst to catalyze MOR. The results indicate that this strategy can be used in the synthesis of other new composite materials with specific hierarchical structures for a more efficient electrocatalytic system.

Modified hemispherectomy for infantile hemiparesis and epilepsy.

OBJECTIVE: To investigate the effect and medical imaging of modified hemispherectomy on patients with infantile hemiparesis and medically refractory epilepsy. PATIENTS AND METHODS: Forty-three patients with infantile hemiparesis and refractory epilepsy who underwent hemispherectomy were enrolled. The treatment effect and medical imaging were analyzed. RESULTS: Anatomical hemispherectomy was successfully performed in all patients (100%). In all patients, the muscular tension decreased and the contracted limbs relaxed. In the pathological examination of the resected brain tissue, secondary cicatricial gyri with concomitant cortical dysplasia was present in 36 cases and polycerebellar gyrus malformation and porencephalia in the other 7 cases. Followed up for 7-15 years (mean 11.3), all patients were alive without a long-term sequela. Epilepsy was satisfactorily controlled, with complete seizure relief in 39 cases (91%) classified as Engel I and basic control in the other 4 (9%) defined as Engel II. The posthemispherectomy medical imaging demonstrated that the intracranial space on the operative side shrank, and the healthy cerebral hemisphere shifted markedly toward the hemispherectomy side, with expanded lateral ventricle on the healthy side and thickened skull and enlarged frontal sinus on the operative side. After 4-5 years, the intracranial space on the operative side disappeared in 75% of the patients, demonstrating enlarged cerebral peduncle on the healthy side. CONCLUSION: Further modified hemispherectomy in patients with infantile hemiparesis and medically refractory epilepsy demonstrated markedly ameliorated effects on epilepsy control and the prevention of superficial cerebral hemosiderosis in the long-term follow-up.

PTEN-silencing combined with ChABC-overexpression in adipose-derived stem cells promotes functional recovery of spinal cord injury in rats.

The efficiency of cell therapy after spinal cord injury (SCI) depend on the survival of transplanted cells. However, sterile microenvironment and glial scar hyperplasia extremely reduce their numbers. Our previous study found overexpression of ChABC gene is positively correlated to migration ability. Expression of PTEN gene is closely associated with proliferation. However, whether manipulation of PTEN and ChABC on adipose-derived mesenchymal stem cells (ADSCs) promote motor recovery is unknown. This study aimed to promote hindlimb function recovery in SCI rats by enhancing proliferation and migration ability of ADSCs, transiently silencing expression of PTEN following overexpression of ChABC (double-gene modified ADSCs, DG-ADSCs). After PTEN silencing, we observed strong proliferation and accelerated G1-S transition in DG-ADSCs using CCK8 assay and flow cytometry. In addition, we demonstrated that migration numbers of DG-ADSCs were higher than control group using Transwell assay. The protein and mRNA levels of MAP2 and ßⅢ-tubulin in DG-ADSCs were increased compared with ADSCs. These results were further confirmed in SCI rats. Increased survival cells and reduction of glial scars were quantitatively analyzed in DG-ADSCs groups, which is definitely correlated to function recovery. Recovery of motor function was observed in DG-ADSCs treatment rats using BBB score, which emphasized that improved viability of transplanted cells and reduction of glial scars were an effective strategy for enhancing recovery of neurological function after SCI.

Investigation on the Component Evolution of a Tetranuclear Nickel-Cluster-Based Metal-Organic Framework in an Electrochemical Oxidation Reaction.

Understanding the active species derived from metal-organic frameworks (MOFs) plays a vital role in the fabrication of highly efficient and stable oxygen evolution reaction (OER) electrocatalysts. Herein, a new alkaline-stable 3D nickel metal-organic framework (Ni-MOF), containing a 1D rod-packing chain structure fused with a tetranuclear nickel cluster [Ni4(µ3-OH)2], is used as a target material to explore its OER properties. The electrocatalytic activities of pure Ni-MOF and hybrid materials made from Ni-MOF with different acetylene black loaded electrodes, such as glassy carbon, fluorine-doped tin oxide, and nickel foam, have been evaluated. Further analysis unravels that the enhanced OER performance might be attributed to the synergistic interactions of two catalytic active species between in situ formed ß-Ni(OH)2 and a tetranuclear Ni4(µ3-OH)2 cluster in Ni-MOF. The findings will shed fresh light on the fabrication of MOF-derived catalysts for efficient electrochemical energy conversion.

Nuclear FAM289-Galectin-1 interaction controls FAM289-mediated tumor promotion in malignant glioma.

BACKGROUND: FAM92A1-289(abbreviated FAM289) is recognized as one of the newly-discovered putative oncogenes. However, its role and molecular mechanisms in promoting cancer progression has not yet been elucidated. This study was performed to reveal its oncogenic functions and molecular mechanisms in human glioblastoma multiforme (GBM) cell models with knockdown or overexpression of FAM289 in vitro and in vivo. METHODS: To elucidate the molecular mechanisms underlying FAM289-mediated tumor progression, the protein-protein interaction between FAM289 and Galectin-1 was verified by co-immunoprecipitation, followed by an analysis of the expression and activity of Galectin-1-associated signaling molecules. Knockdown and overexpression of FAM289 in glioma cells were applied for investigating the effects of FAM289 on cell growth, migration and invasion. The determination of FAM289 expression was performed in specimens from various stages of human gliomas. RESULTS: FAM289-galectin-1 interaction and concomitant activation of the extracellular signal-regulated kinase (ERK) pathway participated in FAM289-mediated tumor-promoting function. Since the expression of DNA methyl transferase 1 (DNMT1) and DNA methyl transferase 3B (DNMT3B) was regulated by FAM289 in U251 and U87-MG glioma cells, Galectin-1 interaction with FAM289 may promote FAM289 protein into the cell nucleus and activate the ERK pathway, thereby upregulating DNMTs expression. Drug resistance tests indicated that FAM289-mediated TMZ resistance was through stem-like property acquisition by activating the ERK pathway. The correlation between FAM289, Galectin-1 expression and the clinical stage of gliomas was also verified in tissue samples from glioblastoma patients. CONCLUSIONS: Our results suggest that high expression of FAM289 in GBM tissues correlated with poor prognosis. FAM289 contributes to tumor progression in malignant glioma by interacting with Galectin-1 thereby promoting FAM289 protein translocation into the cell nucleus. FAM289 in the nucleus activated the ERK pathway, up regulated DNMTs expression and induced stem-like property gene expression which affects drug resistance of glioma cells to TMZ. This study provided functional evidence for FAM289 to be developed as a therapeutic target for cancer treatment.

Comparison of biological characteristics of mesenchymal stem cells derived from the human umbilical cord and decidua parietalis.

Mesenchymal stem cells (MSCs) are derived from the mesoderm and have the self­renewal capacity and multi­directional differentiation potential of adult stem cells. Stem cells from different sources have different molecular and growth characteristics; therefore, the mechanisms and effects of stem cell­mediated repair and tissue regeneration may be different. The aim of the present study was to compare the biological characteristics of MSCs derived from the umbilical cord (UC­MSCs) and MSCs derived from the decidua parietalis (DP­MSCs), and to provide new evidence for the selection of seed cells in regenerative medicine. Growth curves, cell doubling times, colony formation rates, immunophenotypes, differentiation capacities and secretion­factor levels of MSCs derived from the two sources were analysed. UC­MSCs and DP­MSCs exhibited similar properties with regards to morphology, spiral growth, immunophenotype, and potential to differentiate into osteoblasts and adipocytes. For each cell type, the positive rates of the cell surface markers CD73, CD90 and CD105 were >95%, whereas CD34 and CD45 positive rates were <1%. Analyses of in vitro growth kinetics revealed shorter cell­doubling times, and higher proliferative rates and colony formation rates of UC­MSCs compared with DP­MSCs (P<0.05). The concentration of basic fibroblast growth factor in the supernatant from UC­MSCs was higher compared with that from DP­MSCs (P<0.05). However, UC­MSC supernatants exhibited lower levels of of keratinocyte growth factor, vascular endothelial growth factor and stem cell factor compared with DP­MSCs (P<0.05). In conclusion, in vitro characterization of MSCs from these tissue sources revealed a number of common biological properties. However, the results also demonstrated clear biological distinctions and suggested that UC­MSCs may have more effective application prospects.

Multivariate analysis of incision infection after posterior lumbar surgery in diabetic patients: A single-center retrospective analysis.

BACKGROUND: Patients requiring posterior lumbar surgery have increased annually. Incision infection after lumbar surgery has serious consequences for patients. However, data on the related factors of incision infection after lumbar surgery in diabetic patients are limited. Therefore, this study aimed to analyze diabetic patients who underwent lumbar surgery and to explore the risk factors of perioperative incision infection to provide a scientific basis for perioperative intervention of lumbar spine surgery and reduce risk of incision infection in such patients. METHODS: We retrospectively reviewed data of diabetic patients who underwent posterior lumbar surgery from 2011 to 2016. A total of 523 diabetic patients undergoing posterior lumbar surgery were analyzed for the influence of various risk factors on postoperative incision infection. Univariate and multivariate logistic regression was performed. The test level was α=.05, and P < .05 was considered statistically significant. RESULTS: In the past 6 years, among the 523 diabetic patients, the incidence of incision infection after posterior lumbar surgery was approximately 7.1%, of which the shallow incision infection rate was 4.2% and the deep incision infection rate was 2.9%. Incision infection of posterior lumbar surgery in diabetic patients is related to smoking, preoperative glycosylated hemoglobin A1c, postoperative albumin (Alb), surgical segment, operation time, and intraoperative blood loss, especially on postoperative fasting blood glucose, postoperative postprandial blood glucose, local subcutaneous fat thickness, and operation sequence (odds ratio >5.00). Meanwhile, sex, age, body mass index (BMI), preoperative Alb, and newly diagnosed diabetes were not highly correlated with incision infection after posterior lumbar surgery. CONCLUSION: Local subcutaneous fat thickness is a better indicator for predicting incision infection compared with BMI. In diabetic patients undergoing lumbar surgery, actively controlling blood glucose fluctuations, restoring normal diet early after surgery, and optimizing surgical procedures to reduce trauma and operative time can effectively reduce the risk of infection after posterior lumbar surgery.

Characterization of biosurfactant lipopeptide and its performance evaluation for oil-spill remediation.

Biosurfactant lipopeptide is a promising dispersant over varieties of chemical ones in oil-spill remediation. The toxicity, biodegradability and performance of the biosurfactant lipopeptide are studied in this paper.