Abstract
Spin-valley locking in monolayer transition metal dichalcogenides has attracted enormous interest, since it offers potential for valleytronic and optoelectronic applications. Such an exotic ...electronic state has sparsely been seen in bulk materials. Here, we report spin-valley locking in a Dirac semimetal BaMnSb
2
. This is revealed by comprehensive studies using first principles calculations, tight-binding and effective model analyses, angle-resolved photoemission spectroscopy measurements. Moreover, this material also exhibits a stacked quantum Hall effect (QHE). The spin-valley degeneracy extracted from the QHE is close to 2. This result, together with the Landau level spin splitting, further confirms the spin-valley locking picture. In the extreme quantum limit, we also observed a plateau in the
z
-axis resistance, suggestive of a two-dimensional chiral surface state present in the quantum Hall state. These findings establish BaMnSb
2
as a rare platform for exploring coupled spin and valley physics in bulk single crystals and accessing 3D interacting topological states.
Clostridium sporogenes ATCC 3584 is an obligate anaerobe that has been reported to possess excellent tumour‐targeting capacity. Here, we use Cl. sporogenes as a vector to deliver IL‐12, a potent ...antitumour cytokine that bears numerous antitumour properties but that has limited clinical applications due to its strong toxicity when delivered systemically. In this study, Cl. sporogenes was genetically engineered to secrete murine IL‐12, and its antitumour efficacy and toxicity were investigated in a murine EMT6 mammary carcinoma model. After intravenous injection, Cl. sporogenes was able to selectively settle and reproduce in the tumours without encroaching on normal tissues, resulting in a clear delay of tumour growth and a 14·3% cure rate. Importantly, the mice showed no obvious toxicity‐associated side effects, such as diarrhoea and weight loss, during the treatment process. The significant antitumour efficacy and low toxicity of this treatment may be explained by the selective tumour‐targeting properties of Cl. sporogenes and by the sustained release of IL‐12 accompanying bacterial proliferation. This moderate local IL‐12 concentration would not induce the severe response in the entire body, that is inevitable when IL‐12 is administered directly. SIGNIFICANCE AND IMPACT OF THE STUDY: Interleukin‐12 (IL‐12) is a potent antitumour cytokine, but it is toxic when administrated systemically. This study demonstrates that murine IL‐12 can be systemically delivered to hypoxic sites in solid tumours by Clostridium sporogenes, producing a clear delay in tumour growth and a 14·3% cure rate in a mouse tumour model. Importantly, there is no obvious toxicity associated with IL‐12 during the treatment process. This result may be accounted for by the excellent tumour‐targeting capacity of Cl. sporogenes, targeting IL‐12 directly to the tumour site instead of to the entire body.
Deregulation of Shp2, a non-receptor tyrosine phosphatase, causes hyperactivation of extracellular signal-regulated kinase (ERK), leading to growth abnormality. Here, we show that inhibition of ...RhoA-Dia is sufficient to upregulate ERK activation in epithelial cells. Oncogenic Shp2 expression attenuates RhoA-Dia signaling, by which microtubule (MT) is destabilized with reduced level of acetylation. Either MT stabilization, silencing of histone deacetylase 6 (HDAC6) or enforcing RhoA-Dia signal prevents oncogenic Shp2-induced ERK hyperactivation. We provide evidence that downregulation of RhoA-Dia-EB1 pathway by oncogenic Shp2 leads to HDAC6-mediated reduction in MT acetylation, in turn affecting ERK regulation. In response to serum stimulation, cells expressing wild-type Shp2 display transient ERK activation. In contrast, cells expressing oncogenic Shp2 have prolonged ERK activation. HDAC6 inhibition diminishes sustained activation of ERK and slows down the growth of these cells. Likewise, in human cancer cells, blocking Shp2 increases MT acetylation and decreases ERK phosphorylation, which are reversed by inhibition of Dia. As such, HDAC6 inhibition in these cells also reduces ERK activity. Our findings link MT regulation by HDAC6 to oncogenic Shp2 and ERK regulation, implicating the therapeutic potential of HDAC6 inhibitor in diseases involving Shp2 deregulation.
Evaluate the activity of everolimus (RAD001) in combination with octreotide long-acting repeatable (LAR) in patients with advanced low- to intermediate-grade neuroendocrine tumors.
Treatment ...consisted of RAD001 5 mg/d (30 patients) or 10 mg/d (30 patients) and octreotide LAR 30 mg every 28 days. Thirty carcinoid and 30 islet cell patients were enrolled.
Intent-to-treat response rate was 20%. Per protocol, there were 13 with partial responses (22%), 42 with stable disease (SD; 70%), and five patients with progressive disease (8%). Overall median progression-free survival (PFS) was 60 weeks. Median PFS for patients with known SD at entry was longer than for those who had progressive disease (74 v 50 weeks; P < .01). Median overall survival has not been reached. One-, 2-, and 3-year survival rates were 83%, 81%, and 78%, respectively. Among 37 patients with elevated chromogranin A, 26 (70%) achieved normalization or more than 50% reduction. Most common toxicity was mild aphthous ulceration. Grade 3/4 toxicities occurring in >or= 10% of patients included hypophosphatemia (11%), fatigue (11%), and diarrhea (11%). Treatment was associated with a dose-dependent rise in lactate dehydrogenase (LDH). Those with lower than 109 U/L rise in LDH at week 4 had shorter PFS (38 v 69 weeks; P = .01). Treatment was also associated with a decrease in proliferation marker Ki-67 among patients who underwent optional paired pre- and post-treatment biopsy (P = .04).
RAD001 at 5 or 10 mg/d was well tolerated in combination with octreotide LAR, with promising antitumor activity. Confirmatory studies are ongoing.
A porous membrane of carboxymethyl cellulose (CMC) from natural macromolecule as a host of a gel polymer electrolyte for lithium ion batteries is reported. It is prepared, for the first time, by a ...simple non-solvent evaporation method and its porous structure is fine-adjusted by varying the composition ratio of the solvent and non-solvent mixture. The electrolyte uptake of the porous membrane based on CMC is 75.9%. The ionic conductivity of the as-prepared gel membrane saturated with 1 mol L−1 LiPF6 electrolyte at room temperature can be up to 0.48 mS cm−1. Moreover, the lithium ion transference in the gel membrane at room temperature is as high as 0.46, much higher than 0.27 for the commercial separator Celgard 2730. When evaluated by using LiFePO4 cathode, the prepared gel membrane exhibits very good electrochemical performance including higher reversible capacity, better rate capability and good cycling behaviour. The obtained results suggest that this porous polymer membrane shows great attraction to the lithium ion batteries requiring high safety, low cost and environmental friendliness.
•A porous membrane of carboxyl methyl cellulose is prepared by a simple non-solvent evaporation method.•The porous membrane is used as a host of a gel polymer electrolyte for lithium ion batteries.•The lithium ion transference in the gel membrane at room temperature is as high as 0.46.•The prepared gel membrane exhibits very good electrochemical performance.•This porous polymer membrane shows great attraction to the lithium ion batteries.
Tumor cells preferentially adopt aerobic glycolysis for their energy supply, a phenomenon known as the Warburg effect. It remains a matter of debate as to how the Warburg effect is regulated during ...tumor progression. Here, we show that CHIP (carboxyl terminus of Hsc70-interacting protein), a U-box E3 ligase, suppresses tumor progression in ovarian carcinomas by inhibiting aerobic glycolysis. While CHIP is downregulated in ovarian carcinoma, induced expression of CHIP results in significant inhibition of the tumor growth examined by in vitro and in vivo experiments. Reciprocally, depletion of CHIP leads to promotion of tumor growth. By a SiLAD proteomics analysis, we identified pyruvate kinase isoenzyme M2 (PKM2), a critical regulator of glycolysis in tumors, as a target that CHIP mediated for degradation. Accordingly, we show that CHIP regulates PKM2 protein stability and thereafter the energy metabolic processes. Depletion or knockout of CHIP increased the glycolytic products in both tumor and mouse embryonic fibroblast cells. Simultaneously, we observed that CHIP expression inversely correlated with PKM2 levels in human ovarian carcinomas. This study reveals a mechanism that the Warburg effect is regulated by CHIP through its function as an E3 ligase, which mediates the degradation of PKM2 during tumor progression. Our findings shed new light into understanding of ovarian carcinomas and may provide a new therapeutic strategy for ovarian cancer.
A dense instead of porous gel polymer electrolyte for lithium ion batteries is reported for the first time. Its host is a renewable and environment friendly polymer, hydroxyethyl cellulose (HEC). The ...preparation of HEC membrane is very simple. The membrane is stable up to 280°C, much higher than the melting points of those commercial separators based on polyolefin. The evaporation temperature of the organic electrolyte in the prepared gel polymer electrolytes is up to 75°C. In addition, the gel polymer electrolyte shows good electrochemical performance including high ionic conductivity at room temperature, and a high lithium ion transference number. When tested as separator and electrolyte, a LiFePO4 positive electrode displays satisfactory electrochemical properties including high discharge capacity and stable cycling. These results indicate a very promising direction for a low cost and renewable gel polymer electrolyte for lithium ion batteries.
A dense instead of a porous gel polymer electrolyte with high transference number of Li+ ions and good safety. Display omitted
•A renewable and environment friendly cellulose is used to prepare gel polymer electrolyte.•The preparation process is simple.•The prepared polymer membrane is nonporous and dense instead of porous.•The prepared gel polymer electrolyte shows good electrochemical performance.
We present X-ray timing results of the new black hole candidate MAXI J1535−571 during its 2017 outburst from Hard X-ray Modulation Telescope (Insight-HXMT) observations taken from 2017 September 6 to ...23. Following the definitions given by Belloni, we find that the source exhibits transitions from the low/hard state to the hard intermediate state, and eventually to the soft intermediate state. Quasi-periodic oscillations (QPOs) are found in the intermediate states, which suggest different types of QPOs. With the large effective area of Insight-HXMT at high energies, we are able to present the energy dependence of the QPO amplitude and centroid frequency up to 100 keV, which has rarely been explored by previous satellites. We also find that the phase lag at the type-C QPOs centroid frequency is negative (soft lag) and strongly correlated with the centroid frequency. Assuming a geometrical origin of type-C QPOs, the source is consistent with being a high-inclination system.
Aim
To assess the connection between mitophagy and hypoxia‐induced apoptosis in osteoblasts and whether simvastatin alleviates bone resorption in apical periodontitis through modulation of ...mitophagy‐related apoptosis.
Methodology
Hypoxia‐induced generation of reactive oxygen species in mitochondria and changes in mitochondrial membrane potential were evaluated, respectively, by MitoSOX and JC‐1 fluorescence dye signalling. Accumulation of mitophagy markers PTEN‐induced putative kinase 1 (PINK1) and Parkin in mitochondria was examined by Western blotting and immunofluorescence microscopy. Osteoblast apoptosis was assessed by Western analysis of cleaved‐poly (adenosine diphosphate ribose) polymerase (PARP). In a rat model of induced apical periodontitis, the therapeutic effect of simvastatin and its action on osteoblast mitophagy and apoptosis were examined. anova, Fisher's and Student's t‐test were used for data analysis.
Results
Hypoxia‐induced mitochondrial dysfunction and stimulated mitophagy in osteoblasts. Hypoxia also provoked apoptosis in osteoblasts and inhibition of mitophagy decreased hypoxia‐augmented apoptotic activity. Simvastatin alleviated hypoxia‐induced mitochondrial dysfunction, mitophagy and apoptosis. The protective action of simvastatin against apoptosis was related to its antimitophagy activity. Experiments in the rat model of induced apical periodontitis supported the laboratory findings. Simvastatin treatment mitigated periapical bone loss and reduced the activities of apoptosis and mitophagy in regional osteoblasts.
Conclusions
The results suggest that modulation of osteoblast mitophagy may help diminish bone loss associated with inflammation and has potential as an auxiliary therapy for apical periodontitis.
Co-published with What are the institutional politics associated with fostering trans* inclusive policies? When formalizing a policy, what unanticipated challenges may emerge? How are students, ...particularly trans* students, influenced by the implementation of gender-inclusive housing practices and policies? Also, what are campus administrators and practitioners learning from their involvement with the development of trans* work on campus? Housing and Residence Life (HRL) plays an important role in the safety, well-being, and sense of belonging for college students, but gender-inclusive policies and practices in HRL are largely under-explored in student affairs and higher education publications. There are five key objectives that guide this book: 1. To promote and challenge student affairs and higher education staff knowledge about trans* students' identities and experiences; 2. To support and celebrate the accomplishments of educators and professionals in their strides to promote trans* inclusive policies and practices; 3. To highlight the unique role that housing and residence life plays in creating institutional change and serving trans* student populations; 4. To demonstrate the value and use of scholarly personal narratives, particularly for narrating experiences related to implementing trans* inclusive policies in housing and residence life; and 5. To create a strong partnership between scholarship and student affairs practice by developing an avenue for practitioner-scholars to publish their experiences related to gender-inclusive policies in housing and residence life and for others to use these stories to improve their practice. Administrators, educators, and student affairs staff will find this book useful at any stage in the process of creating gender-inclusive housing policies on their campuses.
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