Cascade encapsulation of antimicrobial peptides, exosomes and antibiotics in fibrin-gel for first-aid hemostasis and infected wound healing.

Wounding is one of the most common healthcare problems. Bioactive hydrogels have attracted much attention in first-aid hemostasis and wound healing due to their excellent biocompatibility, antibacterial properties, and pro-healing bioactivity. However, their applications are limited by inadequate mechanical properties. In this study, we first prepared edible rose-derived exosome-like nanoparticles (ELNs) and used them to encapsulate antimicrobial peptides (AMP), abbreviated as ELNs(AMP). ELNs(AMP) showed superior intracellular antibacterial activity, 2.5 times greater than AMP, in in vitro cell infection assays. We then prepared and tested an FDA-approved fibrin-gel of fibrinogen and thrombin encapsulating ELNs(AMP) and novobiocin sodium salt (NB) (ELNs(AMP)/NB-fibrin-gels). The fibrin gel showed a sustained release of ELNs(AMP) and NB over the eight days of testing. After spraying onto the skin, the formulation underwent in situ gelation and developed a stable patch with excellent hemostatic performance in a mouse liver injury model with hemostasis in 31 s, only 35.6 % of the PBS group. The fibrin gel exhibited pro-wound healing properties in the mouse-infected skin defect model. The thickness of granulation tissue and collagen of the ELNs(AMP)/NB-fibrin-gels group was 4.00, 6.32 times greater than that of the PBS group. In addition, the ELNs(AMP)/NB-fibrin-gels reduced inflammation (decreased mRNA levels of TNF-α, IL-1ß, IL6, MCP1, and CXCL1) at the wound sites and demonstrated a biocompatible and biosafe profile. Thus, we have developed a hydrogel system with excellent hemostatic, antibacterial, and pro-wound healing properties, which may be a candidate for next-generation tissue regeneration with a wide clinical application for first-aid hemostasis and infected wound healing.

Asparagine starvation suppresses histone demethylation through iron depletion.

Intracellular α-ketoglutarate is an indispensable substrate for the Jumonji family of histone demethylases (JHDMs) mediating most of the histone demethylation reactions. Since α-ketoglutarate is an intermediate of the tricarboxylic acid cycle and a product of transamination, its availability is governed by the metabolism of several amino acids. Here, we show that asparagine starvation suppresses global histone demethylation. This process is neither due to the change of expression of histone-modifying enzymes nor due to the change of intracellular levels of α-ketoglutarate. Rather, asparagine starvation reduces the intracellular pool of labile iron, a key co-factor for the JHDMs to function. Mechanistically, asparagine starvation suppresses the expression of the transferrin receptor to limit iron uptake. Furthermore, iron supplementation to the culture medium restores histone demethylation and alters gene expression to accelerate cell death upon asparagine depletion. These results suggest that suppressing iron-dependent histone demethylation is part of the cellular adaptive response to asparagine starvation.

Asparagine bioavailability regulates the translation of MYC oncogene.

Amino acid restriction has recently emerged as a compelling strategy to inhibit tumor growth. Recent work suggests that amino acids can regulate cellular signaling in addition to their role as biosynthetic substrates. Using lymphoid cancer cells as a model, we found that asparagine depletion acutely reduces the expression of c-MYC protein without changing its mRNA expression. Furthermore, asparagine depletion inhibits the translation of MYC mRNA without altering the rate of MYC protein degradation. Of interest, the inhibitory effect on MYC mRNA translation during asparagine depletion is not due to the activation of the general controlled nonderepressible 2 (GCN2) pathway and is not a consequence of the inhibition of global protein synthesis. In addition, both the 5' and 3' untranslated regions (UTRs) of MYC mRNA are not required for this inhibitory effect. Finally, using a MYC-driven mouse B cell lymphoma model, we found that shRNA inhibition of asparagine synthetase (ASNS) or pharmacological inhibition of asparagine production can significantly reduce the MYC protein expression and tumor growth when environmental asparagine becomes limiting. Since MYC is a critical oncogene, our results uncover a molecular connection between MYC mRNA translation and asparagine bioavailability and shed light on a potential to target MYC oncogene post-transcriptionally through asparagine restriction.

Machine learning and BP neural network revealed abnormal B cell infiltration predicts the survival of lung cancer patients.

FAM83A gene is related to the invasion and metastasis of various tumors. However, the abnormal immune cell infiltration associated with the gene is poorly understood in the pathogenesis and prognosis of NSCLC. Based on the TCGA and GEO databases, we used COX regression and machine learning algorithms (CIBERSORT, random forest, and back propagation neural network) to study the prognostic value of FAM83A and immune infiltration characteristics in NSCLC. High FAM83A expression was significantly associated with poor prognosis of NSCLC patients (p = 0.00016), and had excellent prognostic independence. At the same time, the expression level of FAM83A is significantly related to the T, N, and Stage. Subsequently, based on machine learing strategies, we found that the infiltration level of naive B cells was negatively correlated with the expression of FAM83A. The low infiltration of naive B cells was significantly related to the poor overall survival rate of NSCLC (p = 0.0072). In addition, Cox regression confirmed that FAM83A and naive B cells are risk factors for the prognosis of NSCLC patients. The nomogram combining FAM83A and naive B cells (C-index = 0.748) has a more accurate prognostic ability than the Stage (C-index = 0.651) system. Our analysis shows that abnormal infiltration of naive B cells associated with FAM83A is a key factor in the prognostic prediction of NSCLC patients.

Effects of corticospinal tract integrity on upper limb motor function recovery in stroke patients treated with repetitive transcranial magnetic stimulation.

BACKGROUND: The bimodal balance-recovery model predicts that corticospinal tract (CST) integrity in the affected hemisphere influences the partterns of brain recovery after stroke. Repetitive transcranial magnetic stimulation (rTMS) has been used to promote functional recovery of stroke patients by modulating motor cortical excitability and inducing reorganization of neural networks. This study aimed to explore how to optimize the efficiency of repetitive transcranial magnetic stimulation to promote upper limb functional recovery after stroke according to bimodal balance-recovery model. METHODS: 60 patients who met the inclusion criteria were enrolled to high CST integrity group (n = 30) or low CST integrity group (n = 30), and further assigned randomly to receive high-frequency rTMS (HF-rTMS), low-frequency rTMS (LF-rTMS) or sham rTMS in addition to routine rehabilitation, with 10 patients in each group. Outcome measures included Fugl-Meyer scale for upper extremity (FMA-UE), Wolf Motor Function (WMFT) scale and Modified Barthel Index (MBI) scale which were evaluated at baseline and after 21 days of treatment. RESULTS: For patients with high CST integrity, the LF group achieved higher FMA-UE, WMFT and MBI scores improvements after treatment when compared to the HF group and sham group. For patients with low CST integrity, after 21 days treatment, only the HF group showed significant improvements in FMA-UE and WMFT scores. For MBI assessment, the HF group revealed significantly better improvements than the LF group and sham group. CONCLUSIONS: For stroke patients with high CST integrity, low-frequency rTMS is superior to high-frequency rTMS in promoting upper limb motor function recovery. However, only high-frequency rTMS can improve upper limb motor function of stroke patients with low CST integrity.

Promoter demethylation of the asparagine synthetase gene is required for ATF4-dependent adaptation to asparagine depletion.

Tumor cells adapt to nutrient-limited environments by inducing gene expression that ensures adequate nutrients to sustain metabolic demands. For example, during amino acid limitations, ATF4 in the amino acid response induces expression of asparagine synthetase (ASNS), which provides for asparagine biosynthesis. Acute lymphoblastic leukemia (ALL) cells are sensitive to asparagine depletion, and administration of the asparagine depletion enzyme l-asparaginase is an important therapy option. ASNS expression can counterbalance l-asparaginase treatment by mitigating nutrient stress. Therefore, understanding the mechanisms regulating ASNS expression is important to define the adaptive processes underlying tumor progression and treatment. Here we show that DNA hypermethylation at the ASNS promoter prevents its transcriptional expression following asparagine depletion. Insufficient expression of ASNS leads to asparagine deficiency, which facilitates ATF4-independent induction of CCAAT-enhancer-binding protein homologous protein (CHOP), which triggers apoptosis. We conclude that chromatin accessibility is critical for ATF4 activity at the ASNS promoter, which can switch ALL cells from an ATF4-dependent adaptive response to ATF4-independent apoptosis during asparagine depletion. This work may also help explain why ALL cells are most sensitive to l-asparaginase treatment compared with other cancers.

Endothelial retinoblastoma protein reduces abdominal aortic aneurysm development via promoting DHFR/NO pathway-mediated vasoprotection.

Cardiovascular disease (CVD) is a major cause of global mortality. The proper functioning of the endothelial layer of arteries is crucial to cardiovascular health. Retinoblastoma protein (Rb), encoded by the Rb1 gene, has been shown to offer vasoprotective effects. Herein, we investigated endothelial Rb's effects on arterial function using an endothelial-specific conditional Rb1 knockout (Rb cKO) mouse model. We found that Rb deficiency reduced dihydrofolate reductase (DHFR) activity and downstream NO production in mouse aortic endothelial cells and blocked arterial vasodilation in an endothelial DHFR-dependent manner. Rb deficiency also increased phenylephrine-triggered arterial vasoconstriction, BP levels, and pathological aortic remodeling without significantly affecting prostanoid synthesis. Employing an angiotensin II (AngII)-stimulated apolipoprotein E knockout (apoE -/-) mice fed a standard, non-atherogenic diet, Rb deficiency increased aortic diameter, stimulated abdominal aortic aneurysm (AAA) development, and reduced survival. These pathological responses to Rb deficiency in AngII-stimulated apoE-/- mice were rescued by DHFR overexpression. Cumulatively, our findings reveal that endothelial Rb positively impacts arterial function by supporting vasoprotective endothelial DHFR/NO pathway activity, leading to reduced AAA development.

Induction of cell death by pyropheophorbide-α methyl ester-mediated photodynamic therapy in lung cancer A549 cells.

Pyropheophorbide-α methyl ester (MPPa) was a promising photosensitizer with stable chemical structure, strong absorption, higher tissue selectivity and longer activation wavelengths. The present study investigated the effect of MPPa-mediated photodynamic treatment on lung cancer A549 cells as well as the underlying mechanisms. Cell Counting Kit-8 was employed for cell viability assessment. Reactive oxygen species levels were determined by fluorescence microscopy and flow cytometry. Cell morphology was evaluated by Hoechst staining and transmission electron microscopy. Mitochondrial membrane potential, cellular apoptosis and cell cycle distribution were evaluated flow-cytometrically. The protein levels of apoptotic effectors were examined by Western blot. We found that the photocytotoxicity of MPPa showed both drug- and light- dose dependent characteristics in A549 cells. Additionally, MPPa-PDT caused cell apoptosis by reducing mitochondrial membrane potential, increasing reactive oxygen species (ROS) production, inducing caspase-9/caspase-3 signaling activation as well as cell cycle arrest at G0 /G1 phase. These results suggested that MPPa-PDT mainly kills cells by apoptotic mechanisms, with overt curative effects, indicating that MPPa should be considered a potent photosensitizer for lung carcinoma treatment.

Identification of Angiotensin I-Converting Enzyme Inhibitory Peptides Derived from Enzymatic Hydrolysates of Razor Clam Sinonovacula constricta.

Angiotensin I-converting enzyme (ACE) inhibitory activity of razor clam hydrolysates produced using five proteases, namely, pepsin, trypsin, alcalase, flavourzyme and proteases from Actinomucor elegans T3 was investigated. Flavourzyme hydrolysate showed the highest level of degree of hydrolysis (DH) (45.87%) followed by A. elegans T3 proteases hydrolysate (37.84%) and alcalase (30.55%). The A. elegans T3 proteases was observed to be more effective in generating small peptides with ACE-inhibitory activity. The 3 kDa membrane permeate of A. elegans T3 proteases hydrolysate showed the highest ACE-inhibitory activity with an IC50 of 0.79 mg/mL. After chromatographic separation by Sephadex G-15 gel filtration and reverse phase-high performance liquid chromatography, the potent fraction was subjected to MALDI/TOF-TOF MS/MS for identification. A novel ACE-inhibitory peptide (VQY) was identified exhibiting an IC50 of 9.8 µM. The inhibitory kinetics investigation by Lineweaver-Burk plots demonstrated that the peptide acts as a competitive ACE inhibitor. The razor clam hydrolysate obtained by A. elegans T3 proteases could serve as a source of functional peptides with ACE-inhibitory activity for physiological benefits.

Sample injection and electrophoretic separation on a simple laminated paper based analytical device.

We described a strategy to perform multistep operations on a simple laminated paper-based separation device by using electrokinetic flow to manipulate the fluids. A laminated crossed-channel paper-based separation device was fabricated by cutting a filter paper sheet followed by lamination. Multiple function units including sample loading, sample injection, and electrophoretic separation were integrated on a single paper based analytical device for the first time, by applying potential at different reservoirs for sample, sample waste, buffer, and buffer waste. As a proof-of-concept demonstration, mixed sample solution containing carmine and sunset yellow were loaded in the sampling channel, and then injected into separation channel followed by electrophoretic separation, by adjusting the potentials applied at the four terminals of sampling and separation channel. The effects of buffer pH, buffer concentration, channel width, and separation time on resolution of electrophoretic separation were studied. This strategy may be used to perform multistep operations such as reagent dilution, sample injection, mixing, reaction, and separation on a single microfluidic paper based analytical device, which is very attractive for building micro total analysis systems on microfluidic paper based analytical devices.

Intestinal Barrier Dysfunction: A Novel Therapeutic Target for Inflammatory Response in Acute Stanford Type A Aortic Dissection.

BACKGROUND: Intestinal barrier dysfunction would lead to a rigorous inflammatory reaction due to the translocation of intestinal lumen-derived bacteria and endotoxins. The aim of the present study was to investigate whether intestinal barrier dysfunction occurs in patients with acute Stanford type A aortic dissection (ATAAD) and to determine its potential relationship with the plasma levels of several inflammatory biomarkers in the progression of ATAAD. DESIGN AND METHODS: Serum samples from a total of 46 patients with ATAAD and 36 healthy volunteers were prospectively collected and analyzed. The serum levels of diamine oxidase (DAO), lactate dehydrogenase (LDH), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and C-reactive protein (CRP) were measured using colorimetric assay, enzyme-linked immunosorbent assay, and immunoturbidimetric assay. RESULTS: Serum levels of DAO, LDH, IL-6, TNF-α, and CRP in patients with ATAAD were significantly higher than those in healthy participants. A significantly positive correlation between DAO activity and IL-6 (r = .56, P < .001), TNF-α (r = .63, P < .001), and CRP (r = .53, P < .001) was observed. Moreover, the activity of DAO correlated negatively with the Pao 2/fraction of inspired oxygen (Fio 2) ratio (r = -.39, P = .007). CONCLUSIONS: Intestinal barrier dysfunction, reflected by an increased level of serum DAO, may play an important role in the development of systemic inflammatory responses in patients with ATAAD. Therefore, strategies of preserving a normal intestinal barrier function may open new horizons in the treatment of inflammation-related adverse events in the setting of ATAAD.

[Proximal Aorta Reconstruction for Type A Aortic Dissection Patients without Intimal Tear in Aortic Arch: the Early and Mid-outcomes].

OBJECTIVE: To evaluate the early and mid-outcomes of proximal aorta reconstruction for type A aortic dissection (AAD) patients without intimal tear in aortic arch, and assess the safety and efficacy of this surgical strategy. METHODS: From January 2010 to February 2013, there were 23 AAD patients without intimal tear in the aortic arch received proximal aorta reconstruction surgery. Clinical data of these patients were analyzed retrospectively, the mean age was (48.04 ± 12.37) years old (21-73 yr.). Twelve cases were acute aortic dissection, the others were chronic dissection. Bentall surgery was performed for 13 cases, Cabrol surgery for 2 cases, Wheat surgery for 1 case, ascending aorta replacement and aortic valve repair was employed for 1 patient, simple ascending aorta replacement for 6 cases. The patients received follow-up every 3 to 6 months after the surgery. RESULTS: The duration of CPB time was (182.83 ± 36.98) min, cardiac arrest time was (111.87 ± 18.82) min, circulatory arrest time was (24.22 ± 6.38) min. The complications were lung infection (4 cases, 17.4%), tracheotomy (2 cases), peritoneal dialysis (1 case), 2 cases suffered transient neurological dysfunction. None stroke, paralysis, and permanent neurological dysfunction occurred. All the patients were discharged. Mean time of follow-up was (38.35 ± 11.95) months (18-56 months). All patients were alive and return to normal life, the proportion of false lumen closure was 65.22% (15 cases). None patients need secondary surgery. CONCLUSION: Proximal aorta reconstruction is safe and effective for AAD patient without intimal tear in aortic arch, the operation strategy can be used individually.

[Preparation and chromatographic performance of a eugenol-bonded silica gel stationary phase for high performance liquid chromatography].

A eugenol-bonded silica gel stationary phase (EGSP) for high performance liquid chromatography ( HPLC) has been synthesized by the solid-liquid successive reaction method. The preparation process included two steps: firstly, γ-glycidoxypropyltrimethoxy-silane (KH-560) was covalently attached to the surface of spherical silica gel. Then the bonded silica gel continued to react with eugenol ligand, which was a plant active component, and obtained EGSP. The structure of EGSP was characterized by elemental analysis, thermogravimetric analysis and Fourier transform infrared spectroscopy. Using naphthalene as a probe, the column efficiency was tested under the mobile phase of acetonitrile-water (35:65, v/v) at a flow rate of 0.8 mL/min. The chromatographic properties and the retention mechanism of EGSP were evaluated by using neutral, basic and acidic analytes as solute probes. Meanwhile, the comparative study with C18 column and phenyl column was also carried out under the same chromatographic conditions. The result showed that the eugenol ligand was successfully bonded to the surface of silica gel with a 0.28 mmol/g of bonded amount, and the theoretical plate number of EGSP column was about 24 707 N/m. The EGSP appeared to be a kind of excellent reversed-phase stationary phase with suitable hydrophobicity and various synergistic sites. The eugenol ligand bonded on silica gel could first provide π-π interaction sites for different analytes because of its benzene ring and alkenyl. In addition, the methoxy groups of eugenol were responsible for dipole-dipole and hydrogen-bonding interactions between the ligand and solutes in the effective separation process. Comparing with traditional C18 column and phenyl column, EGSP has an advantage in the fast separation of polar compounds under simple experimental conditions.

Defining microchannels and valves on a hydrophobic paper by low-cost inkjet printing of aqueous or weak organic solutions.

We describe a simple and cost-effective strategy for rapid fabrication of microfluidic paper-based analytical devices and valves by inkjet printing. NaOH aqueous solution was printed onto a hydrophobic filter paper, which was previously obtained by soaking in a trimethoxyoctadecylsilane-heptane solution, allowing selective wet etching of hydrophobic cellulose to create hydrophilic-hydrophobic contrast with a relatively good resolution. Hexadecyltrimethylammonium bromide (CTMAB)-ethanol solution was printed onto hydrophobic paper to fabricate temperature-controlled valves. At low temperature, CTMAB deposited on the paper is insoluble in aqueous fluid, thus the paper remains hydrophobic. At high temperature, CTMAB becomes soluble so the CTMAB-deposited channel becomes hydrophilic, allowing the wicking of aqueous solution through the valve. We believe that this strategy will be very attractive for the development of simple micro analytical devices for point-of-care applications, including diagnostic testing, food safety control, and environmental monitoring.

[Clinical significances of plasma interleukin-6,C-reaction protein and tumor necrosis factor-alpha in patients with aortic dissection].

OBJECTIVE: To investigate the clinical significances of plasma IL-6, CRP and TNF-alpha concentration changes in aortic dissection. METHODS: Plasma concentrations of IL-6, TNF-alpha and CRP were determined in 68 aortic dissection patients,50 patients with essential hypertensionand 50 healthy volunteers. The changes of plasma IL-6, CRP and TNF-alpha concentration were analyzed in aortic group along with the progression of the disease which was divided into 9 differenttime courses. RESULTS: Compared with essential hypertension and healthy control group, significantly elevated CRP, IL-6 and TNF-alpha concentrations were detected in aortic dissection patients (P<0.05, respectively). All the concentrations of CRP, IL-6 and TNF-alpha reached the peak in acute phase of aortic dissection and then gradually declined in subacute and chronic phase. CONCLUSION: Increased plasma inflammatory factors were significantly associated with aortic dissection.

Time-dependent changes of plasma inflammatory biomarkers in type A aortic dissection patients without optimal medical management.

OBJECTIVES: To investigate the time-dependent changes in plasma levels of interleukin-6, C-reactive protein, and tumor necrosis factor-α in patients with type A aortic dissection (TAAD) who received unoptimal medical management since the onset of dissections. DESIGN AND METHODS: Plasma levels of interleukin-6, C-reactive protein, and tumor necrosis factor-α were detected by ELISA and immuno-turbidimetric assay in 92 TAAD patients at hospital admission. Blood samples from 78 patients with uncontrolled hypertension and 82 healthy volunteers were also analyzed as controls. The occurrence of TAAD-related complication and its relationship with the plasma levels of these inflammatory biomarkers was also investigated. RESULTS: The concentrations of inflammatory mediators were significant higher in TAAD than those in the uncontrolled hypertension and the healthy group. The time to peak plasma level of IL-6.and TNF-α was shorter than that of CRP in TAAD group. In the TAAD group, 51 patients suffered TAAD-related complications, and their plasma level of CRP was significantly higher than that in patients without TAAD-related complications (94.5 ± 58.8 mg/L versus 47.4 ± 47.8 mg/L, p < 0.001). Also, CRP levels strongly correlated with the value of PaO2/FiO2 ratio (r = -0.69, p < 0.001) and creatinine (r = 0.60, p < 0.001). The time to the peak level of CRP was shorter and the duration of persistently high CRP level was longer in the complication group than those in the complication-free group. CONCLUSIONS: Elevated and persistently high levels of plasma CRP, IL-6 and TNF-α were associated with progressively development of the TAAD. The changing pattern of CRP might be a marker for diagnosis and prophylactic treatment of complications. Our findings suggested a critical role of the inflammation in the progression of dissection and TAAD-related complications.

Fabrication of a microfluidic paper-based analytical device by silanization of filter cellulose using a paper mask for glucose assay.

We developed a novel, low-cost and simple method for the fabrication of microfluidic paper-based analytical devices (µPADs) by silanization of filter cellulose using a paper mask having a specific pattern. The paper mask was penetrated with trimethoxyoctadecylsilane (TMOS) by immersing into TMOS-heptane solution. By heating the filter paper sandwiched between the paper mask and glass slides, TMOS was immobilized onto the filter cellulose via the reaction between cellulose OH and TMOS, while the hydrophilic area was not silanized because it was not in contact with the paper mask penetrated with TMOS. The effects of some factors including TMOS concentration, heating temperature and time on the fabrication of µPADs were studied. This method is free of any expensive equipment and metal masks, and could be performed by untrained personnel. These features are very attractive for the fabrication and applications of µPADs in developing countries or resource-limited settings. A flower-shaped µPAD was fabricated and used to determine glucose in human serum samples. The contents determined by this method agreed well with those determined by a standard method.

[Analysis of cytogenetic characteristics in patients with myelodysplastic syndrome].

This study was aimed to investigate the distribution of chromosomal aberrational karyotype in myelodysplastic syndrome (MDS) subgroups, the characterizations of numerical and structural aberration. The chromosome was prepared with simple culture of bone marrow, and the karyotype was analysed by G banding technique. The results showed tht 54 out of 127 patients (42.5%) had clonal chromosome aberrations, and the abnormal rates were different in subgroups: 30% (3/10) in MDS-RA, 35.9% (23/64) in MDS-RCMD, 22.2% (2/9) in MDS-RAS, 45% (9/20) in MDS-RAEB-I, 66.7% (14/21) in MDS-RAEB-II, 100% (3/3) in 5q-syndrome, respectively. Among 54 abnormal chromosome patients, 21 patients showed numerical aberration, 14 patients showed structural aberration, and the other 19 patients showed both numerical and structural aberration. The order of frequent aberrations was as follows complex karyotype (11.02%, 14/127), single +8 (10.24%, 13/127), -7/7q- (3.9%, 5/127), 1q+ (3.15%, 4/127), -X/-Y (3.15%, 4/127), 20q- (2.36%, 3/127), 5q- (2.36%, 3/127). The frequency of complex karyotype in MDS-RAEB (including RAEB-I and RAEB-II) was higher than that in non MDS-RAEB (including RA, RCMD, RAS, 5q-syndrome) (P < 0.05), and the frequency of balanced translocation was lower than that in non-balanced translocation (P < 0.05), and both of the two balanced translocation patients were found in MDS-RAEB. It is concluded that MDS is highly heterogeneous clonal disorder, a great majority of cytogenetic changes can be detected and most of which are recurrent aberrations, balanced translocations are rare, and only found in MDS-RAEB. The frequency of complex karyotype in MDS-RAEB is higher, and the patients with dup (1) (q21q32) recurrent abnormality is common in this study.

[6-(4-Bromo-phen-yl)-2,2'-bipyridine-κN,N']bis-(triphenyl-phosphane-κP)copper(I) tetra-fluoridoborate.

The title compound, [Cu(C(16)H(11)BrN(2))(C(18)H(15)P)(2)]BF(4), is composed of one Cu(I) atom, one 6-(4-bromo-phen-yl)-2,2'-bipyridine (L) ligand, two triphenyl-phosphane mol-ecules and one tetra-fluoridoborate anion. The Cu(I) ion is four-coordinated in a distorted tetra-hedral configuration by two N atoms from L and two P atoms from triphenyl-phosphane ligands. In the L ligand, the two pyridine rings are not coplanar; the mean planes making a dihedral angle of 15.3 (5)°. In the crystal, the ions are linked by weak C-H⋯F inter-actions.