Spontaneous Migration Research Articles

Point and complex defects in monolayer PdSe2 : Evolution of electronic structure and emergence of magnetism

Layered transition-metal dichalcogenides (TMDs) constitute an emerging class of materials that provide researchers a platform to realize fundamental studies and to design promising optoelectronic devices. While defects are an almost unavoidable part of TMDs, they bring additional interesting properties absent in defect-free layers. Moreover, the controlled introduction of defects in TMDs makes it possible to tailor the electromagnetic properties of the materials. Here we report defect-induced properties of single-layer $\mathrm{Pd}{\mathrm{Se}}_{2}$ and demonstrate the emergence of magnetism at the nanoscale. Our first-principle calculations indicate that Se vacancies create in-gap defect states, which can be responsible for trapping of carriers. The complex square ${V}_{\mathrm{Pd}+4\mathrm{Se}}$ vacancy induces spin-polarized states with a total local magnetic moment of $2\phantom{\rule{0.16em}{0ex}}{\ensuremath{\mu}}_{\mathrm{B}}$ per defect, making it possible to introduce magnetization into $\mathrm{Pd}{\mathrm{Se}}_{2}$ and therefore expand the family of two-dimensional (2D) magnets. The defect formation energies are much lower compared to many other TMD materials that can explain the presence of a large number of Se defects after mechanical exfoliation of $\mathrm{Pd}{\mathrm{Se}}_{2}$ layers, while the central location of the Pd atoms preserves them from exfoliation-induced defect formation. The negatively charged vacancies are prone to form and in many cases demonstrate spin-polarized states. The small diffusion barrier of ${\mathrm{V}}_{\mathrm{Se}}$ in 2D $\mathrm{Pd}{\mathrm{Se}}_{2}$ leads to an easy room-temperature migration, while ${\mathrm{V}}_{\mathrm{Pd}}$ demonstrates a high diffusion barrier preventing its spontaneous migration. As a guide for experimentalists, we simulate and characterize scanning tunneling microscope images in valence and conduction states and estimate the electron-beam energy for a controllable production of various defect patterns. These intriguing findings make $\mathrm{Pd}{\mathrm{Se}}_{2}$ an ideal platform to study defect-induced phenomena.

Biochemical and immunological blood parameters in patients with inflammatory complications after spine screw fixation

As a result of screw fixation at the surgical treatment of patients with spinal diseases, certain complications may occur, of which soft tissues inflammation is frequent. Therefore, it is especially important to study the metabolic status of patients before surgery to determine the increased possibility of complications. Objective. To study the biochemical and immunological blood serum parameters and determine their diagnostic sensitivity in patients with the thoracic and lumbar spine diseases after screw fixation with postoperative inflammatory response. Methods. Comparisons of blood parame­ters were carried out in two groups of 20 patients in each group: the first one — patients at whom the postoperative period passed without complications, the second group — a soft tissues inflammation around the metal structure was observed in the postoperative period. Blood for the study was taken before the surgery on an empty stomach for determination of: C-reactive protein (CRP), sialic acid, alkaline phosphatase (ALP) activity, haptoglobin, content of total chondroitin sulfate (ChS), glycoproteins, circulating immune complexes (CIC), the rate of spontaneous lymphocyte mig­ration, the level of lymphocyte migration with antibodies to bone and cartilage antigens. For quantitative characterization of diagnostic reliability of laboratory test was used the criterion of diagnostic sensitivity. Results. In patients with postoperative soft tissue inflammation around the metal device before surgery, the following indicators were the most informative: the content of ChS (95 %), CRP (80 %), glycoproteins (95 %), haptoglobin (92 %), ALP activi­ty (80 %), sialic acid content (90 %), CIC concentration (70 %), the rate of spontaneous lymphocyte migration (65 %). Conclusions. The laboratory parameters complex with the highest diagnostic sensitivity can be recommended for the selection of preventive measures in the preoperative period, which will improve the results of surgical treatment, reduce its duration and costs.

Trained Immunity Confers Prolonged Protection From Listeriosis.

Trained immunity refers to the ability of the innate immune system exposed to a first challenge to provide an enhanced response to a secondary homologous or heterologous challenge. We reported that training induced with β-glucan one week before infection confers protection against a broad-spectrum of lethal bacterial infections. Whether this protection persists over time is unknown. To tackle this question, we analyzed the immune status and the response to Listeria monocytogenes (L. monocytogenes) of mice trained 9 weeks before analysis. The induction of trained immunity increased bone marrow myelopoiesis and blood counts of Ly6Chigh inflammatory monocytes and polymorphonuclear neutrophils (PMNs). Ex vivo, whole blood, PMNs and monocytes from trained mice produced increased levels of cytokines in response to microbial products and limited the growth of L. monocytogenes. In vivo, following challenge with L. monocytogenes, peripheral blood leukocytes were massively depleted in control mice but largely preserved in trained mice. PMNs were reduced also in the spleen from control mice, and increased in the spleen of trained mice. In transwell experiments, PMNs from trained mice showed increased spontaneous migration and CXCL2/MIP2α-induced chemotaxis, suggesting that training promotes the migration of PMNs in peripheral organs targeted by L. monocytogenes. Trained PMNs and monocytes had higher glycolytic activity and mitochondrial respiration than control cells when exposed to L. monocytogenes. Bacterial burden and dissemination in blood, spleen and liver as well as systemic cytokines and inflammation (multiplex bead assay and bioluminescence imaging) were reduced in trained mice. In full agreement with these results, mice trained 9 weeks before infection were powerfully protected from lethal listeriosis. Altogether, these data suggest that training increases the generation and the antimicrobial activity of PMNs and monocytes, which may confer prolonged protection from lethal bacterial infection.

The high rate of spontaneous migration of small size common bile duct stones may allow a significant reduction in unnecessary ERCP and related complications: results of a retrospective, multicenter study.

Common bile duct stones (CBDS) can spontaneously migrate through the duodenal papilla. In this case, ERCP could be unnecessary and a significant rate of complications could be avoided. In this study, we aim at retrospectively evaluating the rate of spontaneous stone passage in patients with an imaging diagnosis of CBDS and at analysing the factors associated to spontaneous stone migration. We conducted a retrospective multi-centre analysis of patients undergoing ERCP for CBDS in a 12-month period. 1016 patients with CBDS were analysed. In all patients CBDS was diagnosed with adequate imaging methods performed prior to ERCP. ERCPs with failed biliary cannulation were excluded. Data regarding patients' characteristics, imaging findings and ERCP procedure were analysed. 1016 patients with CBDS undergoing ERCP were analysed (male sex 43.3%; mean age 69.9 ± 16.5years). Diagnosis of CBDS was obtained by EUS in 415 patients (40.8%), MR in 343 (33.8%), CT in 220 (21.7%), and US in 38 (3.7%). No stones were found at ERCP in 179 patients (17.6%), in 14 (6.2%) when ERCP was performed within 6h from imaging study, in 114 (18.5%) between 7h and 7days, in 32 (24.6%) between 8 and 29days, and in 19 (43.2%) after 30days. The rate of unnecessary ERCP occurred significantly more frequently in patients in whom imaging methods demonstrated either sludge or ≤ 5mm CBDS (29.9 vs. 8.3%; p < 0.001). Spontaneous migration of small CBDS is a frequent event, and ≤ 5mm size and a delay in ERCP > 7days represent predictive factors for it. We suggest that CBDS ≤ 5mm should not undergo immediate removal and this fact would allow reducing the rate of unnecessary ERCP with their related complications. Prospective studies are needed to confirm these results and demonstrate the safety of a conservative management in this setting.

Long-term outcomes of fully covered self-expandable metal stents versus plastic stents in chronic pancreatitis

Chronic pancreatitis (CP) related main pancreatic duct (MPD) stricture has been a challenge for endoscopists. Fully covered self-expandable metal stents (FC-SEMS) has been tried in CP patients, but the efficacy and safety are still controversial. Thus, we aim to compare the long-term clinical efficacy of FC-SEMS vs. plastic stent placement in persistent MPD strictures secondary to CP. Between 2007 and 2018, 80 chronic pancreatitis patients (58 males, median age 49 years), who underwent endoscopic placement of FC-SEMS (n = 26) and plastic stent (n = 54) for persistent MPD strictures after at least 3 months of initial single plastic stenting, were retrospectively analyzed during a median follow-up duration of 33.7 months. As a result, MPD stricture resolution rate was statistically higher in FC-SEMS group (87.0% vs. 42.0%, p < 0.001). Although immediate complications occurred similarly (38.5% vs. 37.0%, p = 0.902), spontaneous migration (26.9%) and de novo strictures (23.1%) were pronounced delayed complications in FC-SEMS group. Pain relief during follow-up was significantly higher in FC-SEMS group (76.9% vs. 53.7%, p = 0.046). The total procedure cost was similar in both groups ($1,455.6 vs. $1,596.9, p = 0.486). In comparison with plastic stent, FC-SEMS placement for persistent MPD strictures had favorable long-term clinical efficacy, with its typical complications like spontaneous migration and de novo strictures.

Obesity enhances the recruitment of mesenchymal stem cells to visceral adipose tissue.

In obesity, high levels of TNF-α in the bone marrow microenvironment induce the bone marrow-mesenchymal stem cells (BM-MSCs) towards a pro-adipogenic phenotype. Here, we investigated the effect of obesity on the migratory potential of BM-MSCs and their fate towards the adipose tissues. BM-MSCs were isolated from male C57Bl/06 mice with high-fat diet-induced obesity. The migratory potential of the BM-MSCs, their presence in the subcutaneous (SAT) and the visceral adipose tissues (VAT), and the possible mechanisms involved were investigated. Obesity did not affect MSC content in the bone marrow but increased the frequency of MSCs in blood, SAT, and VAT. In these animals, the SAT adipocytes presented a larger area, without any changes in adipokine production or the Sdf-1α gene expression. In contrast, in VAT, obesity increased leptin and IL-10 levels but did not modify the size of the adipocytes. The BM-MSCs from obese animals presented increased spontaneous migratory activity. Despite the augmented expression of Cxcr4, these cells exhibited decreased migratory response towards SDF-1α, compared to that of BM-MSCs from lean mice. The PI3K-AKT pathway activation seems to mediate the migration of BM-MSCs from lean mice, but not from obese mice. Additionally, we observed an increase in the spontaneous migration of BM-MSCs from lean mice when they were co-cultured with BM-HCs from obese animals, suggesting a paracrine effect. We concluded that obesity increased the migratory potential of the BM-MSCs and induced their accumulation in VAT, which may represent an adaptive mechanism in response to chronic nutrient overload.

Discrete Modes of Migration Define Human NK Cell Development from Hematopoietic Stem Cells

Human innate lymphoid cells play a critical role in the control of infection and the shaping of the immune response. Furthermore, natural killer (NK) cells are the first reconstituting lymphocyte population after hematopoietic stem cell transplant and play a key role in shaping engraftment and moderating graft vs. leukemic effects. Relative to their adaptive immune counterparts, the molecular interactions that drive innate immune cell differentiation development are poorly understood. Human NK cells arise from bone marrow CD34+ hematopoietic stem cells (HSC) but undergo maturation in distal microenvironments, the best characterized of which is secondary lymphoid tissue. Human NK cells can also be derived in vitro from CD34+ HSC through co-culture with developmentally supportive stromal cells. Despite the requirement for direct stromal cell contact in NK cell maturation, the nature of these contacts is not known. We have previously shown that freshly isolated human NK cell developmental intermediates from in vitro culture, secondary lymphoid tissue or peripheral blood undergo spontaneous migration on the EL08.1D2 stromal cell line. We have further defined the NK cell ‘developmental synapse’, a site of productive and directional signaling in developmental intermediates arrested on stromal cells. Despite these interesting insights, the regulation of, and requirement for, NK cell migration during differentiation has not been defined.To determine the modes of migration associated with human NK cell differentiation, we performed highly resolved continuous live cell imaging of NK cells developing in vitro from CD34+ HSC over 28 days of culture. These analyses were performed in parallel with flow cytometry to monitor the progression of developmental intermediates towards a functionally mature NK cell phenotype. We found that while CD34+ HSC had constrained motility, progressive NK cell differentiation was associated with more directed migratory phenotype. NK cell maturation was associated with increased track length and velocity, and decreased frequency of time of cells spent in arrest on stromal cells. We further defined the acquisition of complex, Levy-walk behavior as has previously been described for mature T cells imaged within tissue. The consistency of these behaviors between in vitro derived cells and fresh ex vivo NK cells isolated from healthy human donors confirms that in vitro differentiation effectively recapitulates migratory phenotypes in addition to functional and cell surface phenotypes associated with NK cell maturation.Together, these data define distinct modes of migration that are acquired by human NK cells. We propose that this reflects a previously unappreciated requirement for cell migration that enables the functional maturation of human NK cells. Better defining the bidirectional signaling between developing NK cells and their microenvironment will enable a complete understanding of the signals that help shape the acquisition of key innate immune cell functions. This understanding is critical for better predicting and therapeutically enhancing lymphocyte reconstitution after transplant. DisclosuresNo relevant conflicts of interest to declare.

Shunt in scrotum: unusual shunt complication in an operated case of post TBM hydrocephalus

The role of shunt placement is to divert cerebrospinal fluid (CSF) from within the ventricles to an alternative location most commonly peritoneal space. Ventriculo Peritoneal Shunt (VPS) is associated with many complications viz over drainage, valve failure, breaking of catheter, catheter obstruction, coiling of catheter, spontaneous knot formation, infection and migration of distal catheter and all of them finally leading to obstructive hydrocephalus. One such complication is distal catheter migration to a rare but possible site i.e. scrotum. We reported a case of scrotal migration of shunt as a late complication of VPS insertion.

Facile bead-to-bead cell-transfer method for serial subculture and large-scale expansion of human mesenchymal stem cells in bioreactors.

The conventional planar culture of adherent cells is inefficient for large‐scale manufacturing of cell and gene therapy products. We developed a facile and efficient bead‐to‐bead cell‐transfer method for serial subculture and large‐scale expansion of human mesenchymal stem cells (hMSCs) with microcarriers in bioreactors. We first compared culture medium with and without nucleosides and found the former maintained the expression of surface markers of hMSCs during their prolonged culture and enabled faster cell proliferation. Subsequently, we developed our bead‐to‐bead cell transfer method to subculture hMSCs and found that intermittent agitation after adding fresh microcarriers to cell‐populated microcarriers could promote spontaneous cell migration to fresh microcarriers, reduce microcarrier aggregation, and improve cell yield. This method enabled serial subculture of hMSCs in spinner flasks from passage 4 to passage 9 without using proteolytic enzymes, which showed faster cell proliferation than the serial planar cultures undergoing multiple enzyme treatment. Finally, we used the medium containing nucleosides and our bead‐to‐bead cell transfer method for cell culture scale‐up from 4‐ to 50‐L cultures in single‐use bioreactors. We achieved a 242‐fold increase in the number of cells to 1.45 × 1010 after 27‐day culture and found that the cells harvested from the bioreactors maintained proliferation ability, expression of their surface markers, tri‐lineage differentiation potential and immunomodulatory property. This study shows the promotive effect of nucleosides on hMSC expansion and the potential of using our bead‐to‐bead transfer method for larger‐scale manufacturing of hMSCs for cell therapy.

Macrophage migration inhibitory factor promotes the migration of dendritic cells through CD74 and the activation of the Src/PI3K/myosin II pathway

Constitutively expressed by innate immune cells, the cytokine macrophage migration inhibitory factor (MIF) initiates host immune responses and drives pathogenic responses in infectious, inflammatory, and autoimmune diseases. Dendritic cells (DCs) express high levels of MIF, but the role of MIF in DC function remains poorly characterized. As migration is critical for DC immune surveillance, we investigated whether MIF promoted the migration of DCs. In classical transwell experiments, MIF-/- bone marrow-derived DCs (BMDCs) or MIF+/+ BMDCs treated with ISO-1, an inhibitor of MIF, showed markedly reduced spontaneous migration and chemotaxis. CD74-/- BMDCs that are deficient in the ligand-binding component of the cognate MIF receptor exhibited a migration defect similar to that of MIF-/- BMDCs. Adoptive transfer experiments of LPS-matured MIF+/+ and MIF-/- and of CD74+/+ and CD74-/- BMDCs injected into the hind footpads of homologous or heterologous mice showed that the autocrine and paracrine MIF activity acting via CD74 contributed to the recruitment of DCs to the draining lymph nodes. Mechanistically, MIF activated the Src/PI3K signaling pathway and myosin II complexes, which were required for the migration of BMDCs. Altogether, these data show that the cytokine MIF exerts chemokine-like activity for DC motility and trafficking.

Spontaneous migration induced Co nanokarstcave encapsulated in N-doped carbon hybrids for efficient oxygen electrocatalyst

Despite the extensive application of porous nanostructures as oxygen electrocatalysts, it is challenging to synthesize single-metal state materials with porous structures, especially the ultrasmall ones due to the uniform diffusion of the same metal. Herein, we pioneer demonstrate a new size effect-based controllable synthesis strategy for the homogeneous Co nanokarstcaves assisted by Co-CN hybrids (CCHs). The preferential migration of cobalt atoms on the surface of small size zeolitic imidazolate framework (ZIF) with high surface energy during pyrolysis is the key factor for the formation of nanokarstcave structure. Furthermore, graphene can act as a diffusion barrier to prevent the agglomeration of nanoparticles in the synthesis process, which also plays an important role in the formation of porous nanostructures. In alkali media, CCHs achieve overpotential of 287 mV (@10 mA·cm−2) for oxygen evolution reaction (OER) and a half wave potential of 0.86 V (vs. RHE) for oxygen reduction reaction (ORR).

Enhanced detectivity of PbS quantum dots infrared photodetector by introducing the tunneling effect of PMMA

With extremely high optical absorption coefficient in infrared regime, lead sulfide (PbS) quantum dots (QDs)-based photodetectors are promising for diverse applications. In recent years, synthesis of materials has made great progress, but the problem of low sensitivity of quantum dots photodetector still unresolved. In this work, the introduction of a tunneling organic layer effectively address this problem. The dark current is decreased by the appropriate thickness of polymethyl methacrylate (PMMA) barrier layer by suppressing the spontaneous migration of ions, and the photogenerated carriers are little effected, thereby the responsivity of the device is improved. As a result, the device exhibits a high responsivity of 3.73 × 105 mA W−1 and a giant specific detectivity of 4.01 × 1013 Jones at a low voltage of −1 V under 1064 nm illumination. In the self-powered mode, the responsivity reaches a value of 157.6 mA W−1, and the detectivity up to 5.9 × 1011 Jones. The performance of the photodetectors is obviously better than most of the reported QDs photodetectors. The design of this device structure provides a new solution to the problem of low sensitivity and high leakage current of quantum dots based infrared photodetectors.

Neutrophil dysfunction in cystic fibrosis

BackgroundExcessive neutrophil inflammation is the hallmark of cystic fibrosis (CF) airway disease. Novel technologies for characterizing neutrophil dysfunction may provide insight into the nature of these abnormalities, revealing a greater mechanistic understanding and new avenues for CF therapies that target these mechanisms. MethodsBlood was collected from individuals with CF in the outpatient clinic, CF individuals hospitalized for a pulmonary exacerbation, and non-CF controls. Using microfluidic assays and advanced imaging technologies, we characterized 1) spontaneous neutrophil migration using microfluidic motility mazes, 2) neutrophil migration to and phagocytosis of Staphylococcal aureus particles in a microfluidic arena, 3) neutrophil swarming on Candida albicans clusters, and 4) Pseudomonas aeruginosa-induced neutrophil transepithelial migration using micro-optical coherence technology (µOCT). ResultsParticipants included 44 individuals: 16 Outpatient CF, 13 Hospitalized CF, and 15 Non-CF individuals. While no differences were seen with spontaneous migration, CF neutrophils migrated towards S. aureus particles more quickly than non-CF neutrophils (p < 0.05). CF neutrophils, especially Hospitalized CF neutrophils, generated significantly larger aggregates around S. aureus particles over time. Hospitalized CF neutrophils were more likely to have dysfunctional swarming (p < 0.01) and less efficient clearing of C. albicans (p < 0.0001). When comparing trans-epithelial migration towards Pseudomonas aeruginosa epithelial infection, Outpatient CF neutrophils displayed an increase in the magnitude of transmigration and adherence to the epithelium (p < 0.05). ConclusionsAdvanced technologies for characterizing CF neutrophil function reveal significantly altered migratory responses, cell-to-cell clustering, and microbe containment. Future investigations will probe mechanistic basis for abnormal responses in CF to identify potential avenues for novel anti-inflammatory therapeutics.

Arhgef6 (alpha-PIX) cytoskeletal regulator signals to GTPases and Cofilin to couple T cell migration speed and persistence.

Immunity is governed by successful T cell migration, optimized to enable a T cell to fully scan its environment without wasted movement by balancing speed and turning. Here we report that the Arhgef6 RhoGEF (aka alpha-PIX; αPIX; Cool-2), an activator of small GTPases, is required to restrain cell migration speed and cell turning during spontaneous migration on 2D surfaces. In Arhgef6-/- T cells, expression of Arhgef7 (beta-PIX; βPIX; Cool-1), a homolog of Arhgef6, was increased and correlated with defective activation and localization of Rac1 and CDC42 GTPases, respectively. Downstream of Arhgef6, PAK2 (p21-activated kinase 2) and LIMK1 phosphorylation was reduced, leading to increased activation of Cofilin, the actin-severing factor. Consistent with defects in these signaling pathways, Arhgef6-/- T cells displayed abnormal bilobed lamellipodia and migrated faster, turned more, and arrested less than wild-type (WT) T cells. Using pharmacologic inhibition of LIMK1 (LIM domain kinase 1) to induce Cofilin activation in WT T cells, we observed increased migration speed but not increased cell turning. In contrast, inhibition of Cdc42 increased cell turning but not speed. These results suggested that the increased speed of the Arhgef6-/- T cells is due to hyperactive Cofilin while the increased turning may be due to abnormal GTPase activation and recruitment. Together, these findings reveal that Arhgef6 acts as a repressor of T cell speed and turning by limiting actin polymerization and lamellipodia formation.

Biophysical Informatics Approach For Quantifying Phenotypic Heterogeneity In Cancer Cell Migration In Confined Microenvironments.

Cancer cell heterogeneity can manifest genetically and phenotypically. Bioinformatics methods have been used to analyze complex genomics and transcriptomics data, but have not been well-established for analyzing biophysical data of phenotypically heterogeneous tumor cells. Here, we take an informatics approach to analyze the biophysical data of MDA-MB-231 cells, a widely used breast cancer cell line, during their spontaneous migration through confined environments. Experimentally, we vary the constriction microchannel geometries (wide channel, short constriction, and long constriction) and apply drug treatments. We find that cells in the short constriction are similar in morphology to the cells in the wide channel. However, their fluorescence profiles are comparable to those in the long constriction. We demonstrate that the cell migratory phenotype is correlated more to mitochondria in a non-confined environment and more to actin in a confined environment. We demonstrate that the cells' migratory phenotypes are altered by ciliobrevin D, a dynein inhibitor, in both confined and non-confined environments. Overall, our approach elucidates phenotypic heterogeneity in cancer cells under confined microenvironments at single-cell resolution. Here, we apply a bioinformatics approach to a single cell invasion assay. We demonstrate that this method can determine distinctions in morphology, cytoskeletal activities, and mitochondrial activities under various geometric constraints and for cells of different speeds. Our approach can be readily adapted to various heterogeneity studies for different types of input biophysical data. In addition, this approach can be applied to studies related to biophysical changes due to differences in external stimuli, such as treatment effects on cellular and subcellular activities, at single-cell resolution. Finally, as similar bioinformatics methods have been widely applied in studies of genetic heterogeneity, biophysical information extracted using this approach can be analyzed together with the genetic data to relate genetic and phenotypic heterogeneity. The data that support the findings of this study are available from the corresponding author upon reasonable request. Supplementary data are available at Bioinformatics online.

Droplet migration on conical fibers.

The spontaneous migration of droplets on conical fibers is studied experimentally by depositing silicone oil droplets onto conical glass fibers. Their motion is recorded using optical microscopy and analyzed to extract the relevant geometrical parameters of the system. The speed of the droplet can be predicted as a function of geometry and the fluid properties using a simple theoretical model, which balances viscous dissipation against the surface tension driving force. The experimental data are found to be in good agreement with the model.

Thrombopoietin Promotes Angiogenesis and Disease Progression in Patients with Multiple Myeloma

Multiple myeloma (MM) progression closely depends on bone marrow (BM) angiogenesis. Several factors sustain angiogenesis, including cytokines, growth factors, and cell-to-cell interactions. Herein, BM thrombopoietin (TPO) was shown to support angiogenesis and disease progression in MM. Patients with MM at different progression phases had higher levels of BM and circulating TPO than monoclonal gammopathy of undetermined significance/smoldering MM patients, suggesting that TPO correlates with disease progression and prognosis. Endothelial cells from patients with monoclonal gammopathy of undetermined significance (MGECs) and endothelial cells from MM (MMECs) expressed TPO receptor, and the TPO treatment triggered their angiogenic capabilities invitro. Indeed, TPO-treated MGECs and MMECs showed enhanced angiogenesis on Matrigel and spontaneous cell migration and chemotaxis by acting as a chemotactic agent. TPO also had an angiogenic activity invivo in the chorioallantoic membrane assay system. Finally, TPO treatment increased the release of active matrix metalloproteinase (MMP)-9 and MMP-2 in MGECs and of MMP-2 in MMECs and affected the balance between angiogenic/antiangiogenic factors in the MM BM. Our results support the angiogenic activity of TPO, and suggest that it may have a critical role in promoting the angiogenic switch during MM progression. Accordingly, TPO may be envisaged as a new angiogenic and prognostic factor in patients with MM.

Numerical analysis on the potential danger zone of compound hazard in gob under mining condition

For years, the methane (CH4) explosion accidents initiated by spontaneous coal combustion took hundreds of lives and destroyed billion possessions in the process of mining. This work developed a fully coupled model involving complex interactions between oxygen transport and airflow, coal spontaneous combustion, CH4 emission and migration. The aim was to analyze the potential danger zone of combined hazard posed by spontaneous coal combustion and CH4 build-up in mine. Unlike traditional fixed mesh that the working face and gob are fixedness, a moving mesh method was incorporated in the model to perform the dynamic gob as the advancing of working face. The moving mesh is modified by the algorithm of Laplace smoothing to avoid mesh distortion and advance the mesh quality. The dynamic distribution characteristics of the porosity, oxygen and CH4 concentration in the gob under mining condition were determined using numerical simulations. According to the theory of the compound hazard, the highest degree of compound hazard zone is identified. The results show that the zone representing the highest degree of compound hazard is located mainly in the middle of the strike directions of the working face, as well as a small part of it on the return airway side and closer to the working face. It was analyzed that the variations in location of potential danger zone under different ventilation flux, the advancing rate of the working face and the attenuation coefficient of CH4 release. Meanwhile, the governance methods for the compound hazard in the gob have been further discussed. This research can provide a guidance on the prediction and control of compound hazard represented by spontaneous coal combustion and methane emission, thus ensuring the safety production.

Clean Solid-Electrolyte/Electrode Interfaces Double the Capacity of Solid-State Lithium Batteries.

Solid-state lithium (Li) batteries using spinel-oxide electrode materials such as LiNi0.5Mn1.5O4 are promising power supplies for mobile devices and electric vehicles. Here, we demonstrate stable battery cycling between the Li0Ni0.5Mn1.5O4 and Li2Ni0.5Mn1.5O4 phases with working voltages of approximately 2.9 and 4.7 V versus Li/Li+ in solid-state Li batteries with contamination-free clean Li3PO4/LiNi0.5Mn1.5O4 interfaces. This clean interface has the effect of doubling the capacity of conventional battery cycling between the Li0Ni0.5Mn1.5O4 and Li1Ni0.5Mn1.5O4 phases. We also investigated the structural changes between the Li0Ni0.5Mn1.5O4 and Li2Ni0.5Mn1.5O4 phases during battery cycling. Furthermore, we found an inhomogeneous distribution of the Li2Ni0.5Mn1.5O4 phase in the LiNi0.5Mn1.5O4 electrode, induced by spontaneous Li migration after the formation of the Li3PO4/LiNi0.5Mn1.5O4 interface. These results indicate that the formation of a contamination-free clean Li3PO4/LiNi0.5Mn1.5O4 interface is key to increase the battery capacity.

Spontaneous Ion Migration via Mechanochemical Ultrasonication in Mixed Halide Perovskite Phase Formation: Experimental and Theoretical Insights.

We present a simple yet powerful synthesis process to prepare compound-phase perovskite nanoparticles (MAPbX3-nYn; MA = CH3NH3+ and X/Y = I, Br, or Cl). This is achieved by mixing two pure-phase perovskites (MAPbX3 and MAPbY3) by using ultrasonic vibration as a mechanochemical excitation. Unlike conventional methods, this procedure does not require any effort in designing a reaction or choosing any particular precursor. X-ray diffraction and TEM studies confirm compound-phase formation in all possible stoichiometries. The origin behind ultrasonic mixing lies in the generation of mechanical stress and high temperature arising from acoustic cavitation during reaction. Long-term experimental stability of the compound-phase is comprehended theoretically by simulating the temperature-dependent Gibbs free energy. Negative mixing entropy plays a crucial role during the synthesis which leads to better stabilization of the compound-phase perovskite over the pure-phase. The ease of synthesis and remarkable phase stability make this process effective and less cumbersome for perovskite nanoparticle synthesis.