Effects of layer number and initial pressure on continuum-based buckling analysis of multi-walled carbon nanotubes accounting for van der Waals interaction

The structural instability of multi-walled carbon nanotubes(MWCNTs) has captured extensive attention due to the unique characteristic of extremely thin hollow cylinder structure. The previous studies usually focus on the buckling behavior without considering the effects of the wall number and initial pressure. In this paper, the axial buckling behavior of MWCNTs with the length-to-outermost radius ratio less than 20 is investigated within the framework of the Donnell shell theory. The governing equations for the infinitesimal buckling of MWCNTs are established, accounting for the van der Waals(vd W) interaction between layers. The effects of the wall number, initial pressure prior to buckling, and aspect ratio on the critical buckling mode, buckling load, and buckling strain are discussed, respectively. Specially, the four-walled and twenty-walled CNTs are studied in detail, indicating the fact that the buckling instability may occur in other layers besides the outermost layer. The obtained results extend the buckling analysis of the continuum-based model, and provide theoretical support for the application of CNTs.

China's climate socialization and renewable energy coalition building

Against the backdrop of a heavy carbon lock-in energy structure,China has made considerable progress in renewable energy(RE)development and become a world leader in this area within a decade.Although existing research suggests that rapid RE growth is mainly due to the convergence of economic growth,green industry competition,and energy security concerns under a unique state-led model,they oversimplify the difficulty inherent in RE policy shifting supported by formerly weak pro-RE actors in China's historical trajectory of a low-carbon transition.By exploring the interaction between international and domestic actors by means of a socialization-based coalition-building framework,this paper aims at analyzing how the capacity building of the RE coalition gets enhanced via institutional anchoring and resource reallocation in the climate socialization process and how the strengthened RE coalition has spurred transformation in China's RE policy and the challenges they are confronted with.

An intravascular needle coated by ZnO nanoflowers for in vivo elimination of circulating tumor cells

Circulating tumor cells(CTCs)are recognized as the main source of tumor recurrence and metastasis.Eliminating the CTCs in peripheral blood provides a new strategy to reduce the probability of recurrence or metastasis.Here,we proposed a concept to eliminate CTCs by inserting a needle in the superficial blood vessel.Using the property of ZnO and the structure of nanoflowers,we designed a medical needle coated with ZnO nanoflowers(ZNFs),which killed about 90%of captured CTCs in vitro and prevented the injecting CTCs from spreading to lung tissue in BABL/c mouse model.Results in vitro and in vivo demonstrated that the CTCs not only were captured and killed,but also detached from the needle surface after dead,enabling the ZNFs needle continually eliminate CTCs.Furthermore,a theoretical model was presented to explain the penetration mechanism of cells by nanostructures,which indicated that nanoflowers structure can puncture CTCs more easily than vertical nanowire structure.The concept of inserting an intravascular needle provides a potential strategy to lower the concentration of CTCs in blood and reduce the probability of tumor recurrence or metastasis.

PEP06 polypeptide 30 is a novel clusterdissociating agent inhibiting αv integrin/FAK/Src signaling in oral squamous cell carcinoma cells

Collectively migrating tumor cells have been recently implicated in enhanced metastasis of epithelial malignancies.In oral squamous cell carcinoma(OSCC),av integrin is a crucial mediator of multicellular clustering and collective movement in vitro;however,its contribution to metastatic spread remains to be addressed.According to the emerging therapeutic concept,dissociation of tumor clusters into single cells could significantly suppress metastasis-seeding ability of carcinomas.This study aimed to investigate the anti-OSCC potential of novel endostatin-derived polypeptide PEP06 as a clusterdissociating therapeutic agent in vitro.Firstly,we found marked enrichment ofαv integrin in collectivelyinvading multicellular clusters in human OSCCs.Our study revealed that metastatic progression of OSCC was associated with augmented immunostaining of av integrin in cancerous lesions.Following PEP06treatment,cell clustering on fibronectin,migration,multicellular aggregation,anchorage-independent survival and colony formation of OSCC were significantly inhibited.Moreover,PEP06 suppressed av integrin/FAK/Sre signaling in OSCC cells.PEP06-induced loss of active Src and E-cadherin from cell-cell contacts contributed to diminished collective migration of OSCC in vitro.Overall,these results suggest that PEP06 polypeptide 30 inhibiting av integrin/FAK/Src signaling and disrupting E-cadherin-based intercellular junctions possesses anti-metastatic potential in OSCC by acting as a cluster-dissociating therapeutic agent.

S1P/S1PR1 signaling differentially regulates the allogeneic response of CD4 and CD8 T cells by modulating mitochondrial fission

Graft-versus-host disease (GVHD) significantly contributes to patient morbidity and mortality after allogeneic hematopoietic cell transplantation (allo-HSCT). Sphingosine-1-phosphate (S1P) signaling is involved in the biogenetic processes of different immune cells. In the current study, we demonstrated that recipient sphingosine kinase 1 (Sphk1), but not Sphk2, was required for optimal S1PR1-dependent donor T-cell allogeneic responses by secreting S1P. Using genetic and pharmacologic approaches, we demonstrated that inhibition of Sphk1 or S1PR1 substantially attenuated acute GVHD (aGVHD) while retaining the graft-versus-leukemia (GVL) effect. At the cellular level, the Sphk1/S1P/S1PR1 pathway differentially modulated the alloreactivity of CD4+ and CD8+ T cells;it facilitated T-cell differentiation into Th1/Th17 cells but not Tregs and promoted CD4+ T-cell infiltration into GVHD target organs but was dispensable for the CTL activity of allogeneic CD8+ T cells. At the molecular level, the Sphk1/S1P/S1PR1 pathway augmented mitochondrial fission and increased mitochondrial mass in allogeneic CD4+ but not CD8+ T cells by activating the AMPK/AKT/mTOR/Drp1 pathway, providing a mechanistic basis for GVL maintenance when S1P signaling was inhibited. For translational purposes, we detected the regulatory efficacy of pharmacologic inhibitors of Sphk1 and S1PR1 in GVHD induced by human T cells in a xenograft model. Our study provides novel mechanistic insight into how the Sphk1/S1P/S1PR1 pathway modulates T-cell alloreactivity and validates Sphk1 or S1PR1 as a therapeutic target for the prevention of GVHD and leukemia relapse. This novel strategy may be readily translated into the clinic to benefit patients with hematologic malignancies and disorders.

Reverse effect of Semaphorin-3F on rituximab resistance in diffuse large B-cell lymphoma via the Hippo pathway

Background:Exploring the underlying mechanism of rituximab resistance is critical to improve the outcomes of patients with diffuse large B-cell lymphoma(DLBCL).Here,we tried to identify the effects of the axon guidance factor semaphorin-3F(SEMA3F)on rituximab resistance as well as its therapeutic value in DLBCL.Methods:The effects of SEMA3F on the treatment response to rituximab were investigated by gain-or loss-of-function experiments.The role of the Hippo pathway in SEMA3F-mediated activity was explored.A xenograft mouse model generated by SEMA3F knockdown in cells was used to evaluate rituximab sensitivity and combined therapeutic effects.The prognostic value of SEMA3F and TAZ(WW domain-containing transcription regulator protein 1)was examined in the Gene Expression Omnibus(GEO)database and human DLBCL specimens.Results:We found that loss of SEMA3F was related to a poor prognosis in patients who received rituximab-based immunochemotherapy instead of chemotherapy regimen.Knockdown of SEMA3F significantly repressed the expression of CD20 and reduced the proapoptotic activity and complement-dependent cytotoxicity(CDC)activity induced by rituximab.We further demonstrated that the Hippo pathway was involved in the SEMA3F-mediated regulation of CD20.Knockdown of SEMA3F expression induced the nuclear accumulation of TAZ and inhibited CD20 transcriptional levels via direct binding of the transcription factor TEAD2 and the CD20 promoter.Moreover,in patients with DLBCL,SEMA3F expression was negatively correlated with TAZ,and patients with SEMA3F^(low)TAZ^(high)had a limited benefit from a rituximab-based strategy.Specifically,treatment of DLBCL cells with rituximab and a YAP/TAZ inhibitor showed promising therapeutic effects in vitro and in vivo.Conclusion:Our study thus defined a previously unknown mechanism of SEMA3F-mediated rituximab resistance through TAZ activation in DLBCL and identified potential therapeutic targets in patients.

Mg对原位自生TiB_(2)/Al-4.5Cu复合材料微观组织及力学性能的影响

采用Al-K2TiF6-KBF4混合盐原位自生反应法,制备了不同Mg质量分数的3wt%TiB2/Al-4.5Cu复合材料。采用SEM、TEM、HM硬度测试和室温拉伸等方法研究了Mg含量和多级热处理对3wt%TiB2/Al-4.5Cu复合材料微观组织和力学性能的影响。微观组织观察发现:Mg质量分数为3wt%时,经过多级热处理后,TiB2颗粒的团聚现象明显改善,反应生成的TiB2颗粒平均尺寸约为130 nm,基体内伴随有大量弥散分布的纳米级颗粒,且α-Al的晶粒尺寸也明显减小。力学测试结果表明:多级热处理后,3wt%TiB2/Al-4.5Cu复合材料的硬度和抗拉强度随Mg含量的增加而提高,但过量的Mg (≥4wt%)会造成TiB2颗粒细化效果下降。分析表明:Mg的加入能够降低TiB2/α-Al界面能,减少脆性相Al3Ti、 Al2B的生成,并通过反应生成的MgAl2O4使界面结构变成TiB2/MgAl2O4/α-Al,从而有效抑制了TiB2的团聚,改善了TiB2颗粒与Al液界面的润湿性,提高了形核率,进一步细化了α-Al晶粒尺寸。