Vertices with the Second Neighborhood Property in Eulerian Digraphs

The Second Neighborhood Conjecture states that every simple digraph has a vertex whose second out-neighborhood is at least as large as its first out-neighborhood, i.e. a vertex with the Second Neighborhood Property. A cycle intersection graph of an even graph is a new graph whose vertices are the cycles in a cycle decomposition of the original graph and whose edges represent vertex intersections of the cycles. By using a digraph variant of this concept, we prove that Eulerian digraphs which admit a simple dicycle intersection graph have not only adhere to the Second Neighborhood Conjecture, but have a vertex of minimum outdegree that has the Second Neighborhood Property.Comment: fixed an error in an earlier version and made structural change

Crystal structure of tubulin folding cofactor A from Arabidopsis thaliana and its β-tubulin binding characterization

AbstractMicrotubules are composed of polymerized α/β-tubulin heterodimers. Biogenesis of assembly-competent tubulin dimers is a complex multistep process that requires sequential actions of distinct molecular chaperones and cofactors. Tubulin folding cofactor A (TFCA), which captures β-tubulin during the folding pathway, has been identified in many organisms. Here, we report the crystal structure of Arabidopsis thaliana TFC A (KIESEL, KIS), which forms a monomeric three-helix bundle. The functional binding analysis demonstrated that KIS interacts with β-tubulin in plant. Furthermore, mutagenesis studies indicated that the α-helical regions of KIS participate in β-tubulin binding. Unlike the budding yeast TFC A, the two loop regions of KIS are not required for this interaction suggesting a distinct binding mechanism of TFC A to β-tubulin in plants.Structured summaryMINT-7968902, MINT-7968915, MINT-7968951, MINT-7968966: KIS (uniprotkb:O04350) physically interacts (MI:0915) with Tub9 (uniprotkb:P29517) by anti tag coimmunoprecipitation (MI:0007)MINT-7968928: KIS (uniprotkb:O04350) and Tub9 (uniprotkb:P29517) physically interact (MI:0915) by bimolecular fluorescence complementation (MI:0809

KMT2A promotes melanoma cell growth by targeting hTERT signaling pathway.

Melanoma is an aggressive cutaneous malignancy, illuminating the exact mechanisms and finding novel therapeutic targets are urgently needed. In this study, we identified KMT2A as a potential target, which promoted the growth of human melanoma cells. KMT2A knockdown significantly inhibited cell viability and cell migration and induced apoptosis, whereas KMT2A overexpression effectively promoted cell proliferation in various melanoma cell lines. Further study showed that KMT2A regulated melanoma cell growth by targeting the hTERT-dependent signal pathway. Knockdown of KMT2A markedly inhibited the promoter activity and expression of hTERT, and hTERT overexpression rescued the viability inhibition caused by KMT2A knockdown. Moreover, KMT2A knockdown suppressed tumorsphere formation and the expression of cancer stem cell markers, which was also reversed by hTERT overexpression. In addition, the results from a xenograft mouse model confirmed that KMT2A promoted melanoma growth via hTERT signaling. Finally, analyses of clinical samples demonstrated that the expression of KMT2A and hTERT were positively correlated in melanoma tumor tissues, and KMT2A high expression predicted poor prognosis in melanoma patients. Collectively, our results indicate that KMT2A promotes melanoma growth by activating the hTERT signaling, suggesting that the KMT2A/hTERT signaling pathway may be a potential therapeutic target for melanoma

The H 2

Aims. To examine the expression patterns of hydrogen sulphide- (H2S-) producing enzymes in ischaemic heart tissue and plasma levels of H2S after 2 weeks of NaHS treatment after myocardial infarction (MI) and to clarify the role of endogenous H2S in the MI process. Results. After MI surgery, 2 weeks of treatment with the H2S donor NaHS alleviated ischaemic injury. Meanwhile, in ischemia myocardium, three H2S-producing enzymes, cystathionine γ-lyase (CSE), cystathionine-β-synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (3-MST) significantly increased. Plasma H2S levels were also elevated. In vitro, NaHS treatment protected cardiomyocytes from hypoxic injury and raised CBS levels in a concentration-dependent manner. Different from in vivo results, however, CSE or 3-MST expression did not change. NaHS treatment increased the activity of CSE/CBS but not of 3-MST. When CSE was either knocked down (in vitro) or knocked out (in vivo), H2S levels significantly decreased, which subsequently exacerbated the ischaemic injury. Meanwhile, the expressions of CBS and 3-MST increased due to compensation. Conclusions. Exogenous H2S treatment changed the expressions of three H2S-producing enzymes and H2S levels after MI, suggesting a new and indirect regulatory mechanism for H2S production and its contribution to cardiac protection. Endogenous H2S plays an important role in protecting ischaemic tissue after MI

Influence of intermetallic Al-Mn particles on in-situ steam Mg-Al-LDH coating on AZ31 magnesium alloy

The influence of intermetallic Al-Mn particles on the corrosion behavior of in-situ formed Mg-Al layered double hydroxide (Mg-Al-CO32--LDH) steam coating on AZ31 Mg alloy was investigated. The alloy was pretreated with H3PO4, HCl, HNO3 or citric acid (CA), followed by hydrothermal treatment, for the fabrication of Mg-Al-LDH coating. The microstructure, composition and corrosion resistance of the coated samples were investigated. The results showed that the surface area fraction of Al-Mn phase exposed on the surface of the alloy was significantly increased after CA pretreatment, which promotes the growth of the Mg-Al-LDH steam coating. Further, the LDH-coated alloy pretreated with CA possessed the most compact surface and the maximum coating thickness among all the coatings. The corrosion current density of the coated alloy was decreased by three orders of magnitude as compared to that of the bare alloy

Corrosion resistance of Mg-Al-LDH steam coating on AZ80 Mg alloy: Effects of citric acid pretreatment and intermetallic compounds

In this study, the effects of intermetallic compounds (Mg17Al12 and Al8Mn5) on the Mg-Al layered double hydroxide (LDH) formation mechanism and corrosion behavior of an in-situ LDH/Mg(OH)2 steam coatings on AZ80 Mg alloy were investigated. Citric acid (CA) was used to activate the alloy surface during the pretreatment process. The alloy was first pretreated with CA and then subjected to a hydrothermal process using ultrapure water to produce Mg-Al-LDH/Mg(OH)2 steam coating. The effect of different time of acid pretreatment on the activation of the intermetallic compounds was investigated. The microstructure and elemental composition of the obtained coatings were analyzed using FE-SEM, EDS, XRD and FT-IR. The corrosion resistance of the coated samples was evaluated using different techniques, i.e., potentiodynamic polarization (PDP), electrochemical impedance spectrum (EIS) and hydrogen evolution test. The results indicated that the CA pretreatment significantly influenced the activity of the alloy surface by exposing the intermetallic compounds. The surface area fraction of Mg17Al12 and Al8Mn5 phases on the surface of the alloy was significantly higher after the CA pretreatment, and thus promoted the growth of the subsequent Mg-Al-LDH coatings. The CA pretreatment for 30 s resulted in a denser and thicker LDH coating. Increase in the CA pretreatment time significantly led to the improvement in corrosion resistance of the coated AZ80 alloy. The corrosion current density of the coated alloy was lower by three orders of magnitude as compared to the uncoated alloy

The genetic load for hereditary hearing impairment in Chinese population and its clinical implication

AbstractObjectiveTo understand the genetic load in the Chinese population for improvement in diagnosis, prevention and rehabilitation of deafness.MethodsDNA samples, immortalized cell lines as well as detailed clinical and audiometric data were collected through a national genetic resources collecting network. Two conventional genetic approaches were used in the studies. Linkage analysis in X chromosome and autosomes with microsatellite markers were performed in large families for gene mapping and positional cloning of novel genes. Candidate gene approach was used for screening themtDNA 12SrRNA, GJB2andSLC26A4mutations in population–based samples.ResultsA total of 2, 572 Chinese hearing loss families or sporadic cases were characterized in the reported studies, including seven X–linked, one Y–linked, 28 large and multiplex autosomal dominant hearing loss families, 607 simplex autosomal recessive hereditary hearing loss families, 100 mitochondrial inheritance families, 147GJB2induced hearing loss cases, 230 cases with enlarged vestibular aqueduct (EVA) syndrome, 169 sporadic cases with auditory neuropathy, and 1, 283 sporadic sensorineural hearing loss cases. Through linkage analysis or sequence analysis, two X–linked families were found transmitting two novel mutations in thePOU3F4gene, while another X–linked family was mapped onto a novel locus, nominated asAUNX1(auditory neuropathy, X–linked locus 1). The only Y–linked family was mapped onto theDFNY1locus (Y–linked locus 1,DFNY1). Eight of the 28 autosomal dominant families were linked to various autosomal loci. In population genetics studies, 2, 567 familial cases and sporadic patients were subjected to mutation screening for three common hearing loss genes:mtDNA 12S rRNA 1555G, GJB2andSLC26A4.The auditory neuropathy cases in our samples were screened forOTOFgene mutations.ConclusionsThese data show that the Chinese population has a genetic load on hereditary hearing loss. Establishing personalized surveillance and prevention models for hearing loss based on genetic research will provide the opportunity to decrease the prevalence of deafness in the Chinese population

In vitro degradation and biocompatibility of vitamin C loaded Ca-P coating on a magnesium alloy for bioimplant applications

Molecular recognition was utilized to fabricate bioinspired calcium phosphate (Ca-P) coating on bioabsorbable magnesium alloys through small biomolecules such as Vitamin C (VC). Ca-P and VC hybrid coating (Ca-PVC) was successfully fabricated on AZ31 Mg alloy. The surface morphology and chemical composition of the coatings were investigated using SEM, XRD, and FTIR together with XPS. The results showed that the Ca-PVC coating was composed of bamboo leaf-like Ca-P particles with a thickness of about three times that of the Ca-P coating. The surface roughness of the Ca-PVC coating (1.12 ± 0.12 µm) was lower than that (3.14 ± 1.93 µm) of Ca-P coating, suggesting the formation of refined Ca-P particles resulting from the VC addition. The corrosion resistance of the coated samples was characterized via electrochemical polarization, impedance spectroscopy, and immersion hydrogen evolution tests. The cell toxicity of the coated samples was evaluated utilizing mouse MC3T3-E1 pre-osteoblasts. The charge transfer resistance (Rct) of the Ca-PVC coated alloy increased as compared to the bare and Ca-P coated alloy samples. The Ca-PVC coated alloy exhibited minimal corrosion current density (1.36 × 10−6 A cm−2), which is one order of magnitude lower in comparison to that of the Ca-P coated alloy. These results confirm that VC addition greatly enhanced the coating resistance on AZ31 Mg alloy. It was also noticed that the Ca-PVC coated samples rapidly induced the formation of apatite after immersion in Hank's solution. VC was mainly transformed to L-Threonic acid, which facilitated the nucleation process of the Ca-PVC coating and significantly increased the thickness, density, and bonding strength of the coating. With enhanced corrosion resistance property and excellent biocompatibility, Ca-PVC coating has great potential for application in biodegradable Mg-based alloys

On-demand plerixafor added to high-dose cyclophosphamide and pegylated recombinant human granulocyte colony-stimulating factor in the mobilization of patients with multiple myeloma: a treatment with high effectiveness, convenient, and affordable cost

ObjectiveThe combination of high-dose cyclophosphamide (HD-Cy) (3g/m2) plus granulocyte colony-stimulating factor (G-CSF) and on-demand plerixafor (PXF) has been considered an effective mobilization regimen of patients with multiple myeloma(MM). However, the daily multi-injection regimen of G-CSF poses challenges. This study delves into the efficiency and cost implications of a novel approach, using HD-Cy alongside pegylated G-CSF (PEG G-CSF) and on-demand PXF. Unlike G-CSF, which necessitates daily injections, the half-life of PEG G-CSF extended allows for a single injection.MethodsA retrospective analysis was conducted on 350 MM patients, which were categorized based on their mobilization regimens: Cy+PEG G-CSF+/-PXF (n=66), Cy+PEG G-CSF (n=91), Cy+ G-CSF (n=169), and G-CSF+PXF (n=24).ResultsMobilization with Cy+PEG G-CSF+/-PXF(8.79)yielded a notably higher median CD34+ cell count compared to the other regimens: Cy+PEG G-CSF(4.96), Cy+G-CSF (4.65), and G-CSF+PXF (2.99) (P<0.001). The percentage of patients who achieved >6×106/kg CD34+ cells was significantly higher in the Cy+PEG G-CSF+/-PXF group (77.3%) than in the other mobilization regimens: Cy+PEG G-CSF (41.8%), Cy+ G-CSF (37.3%), and G-CSF+PXF (8.3%) (P<0.001). From a cost perspective, the Cy+PEG G-CSF+/-PXF approach was more economical than the G-CSF+PXF strategy but was marginally costlier than the other two methods. A multivariate assessment highlighted that the combination of Cy+PEG G-CSF with on-demand PXF had a superior potential to achieve the desired harvest (6×106/kg) compared to the Cy+PEG G-CSF protocol without PXF. The incremental cost-effectiveness ratio for each 1% increase in the probability of achieving a successful optimal harvest was $ 97.02 per patient. The incidence of neutropenic fever was 3.0% in the Cy+PEG G-CSF+/-PXF group.ConclusionThe combination of on-demand PXF with HD-Cy and PEG G-CSF offers a cost-effective approach with a high mobilization success rate, manageable side effects, and the convenience of fewer injections. It stands as a promising mobilization strategy for MM patients

Meta-Analysis on the Efficacy and Safety of Hyperbaric Oxygen as Adjunctive Therapy for Vascular Dementia

Background: Vascular dementia (VD) is a common type of disease in the elderly. Numerous clinical trials have suggested that hyperbaric oxygen is an effective and safe complementary therapy for aging-related disorders. However, there is no reliable systematic evidence regarding hyperbaric oxygen therapy (HBOT) for the treatment of VD. Therefore, we performed a meta-analysis to evaluate the clinical efficacy and safety of HBOT in treating VD.Methods: We methodically retrieved the clinical studies from eight databases (PubMed, Cochrane Library, Embase, Web of Science, Sino-Med, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and WanFang) from their inception to November 2018. RevMan 5.3.5 was used for quality assessment and data analysis. Stata 15.1 was employed for publication bias detection and sensitivity analysis.Results: Twenty-five randomized clinical trials (RCTs) involving 1,954 patients met our inclusion criteria. These articles researched the HBOT + oxiracetam + conventional therapy (CT) vs. oxiracetam + CT (n = 13), HBOT + butylphthalide +CT vs. butylphthalide + CT (n = 5), HBOT + donepezil + CT vs. donepezil + CT (n = 4), HBOT + nicergoline + CT vs. nicergoline + CT (n = 2) and HBOT + CT vs. CT (n = 1). The results indicated that additional HBOT strikingly improved the Mini-Mental State Examination (MMSE) (MD = 4.00; 95% CI = 3.28–4.73; P < 0.00001), activities of daily living (ADL) (MD = −5.91; 95% CI = −6.45, −5.36; P < 0.00001) and ADL by Barthel index (BADL) (MD = 13.86; 95% CI = 5.63–22.10; P = 0.001) and increased the total efficacy rate (TEF) (OR = 4.84, 95% CI = 3.19–7.33, P < 0.00001). The adverse events rates were not statistically significant between the HBOT and CT groups (OR = 0.85, 95% CI = 0.26–2.78, P = 0.79).Conclusion: In view of the effectiveness and safety of HBOT, the present meta-analysis suggested that HBOT can be recommended as an effective and safe complementary therapy for the treatment of VD.Protocol Registration: PROSPERO (ID: CRD42019117178). Available online at: http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42019117178