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The tumor microenvironment induces immunosuppression via recruiting and expanding suppressive immune cells such as regulatory T cells (Treg) to promote cancer progression. In this study, we documented that tumor-infiltrating CD73+ γδTregs were the predominant Tregs in human breast cancer and exerted more potent immunosuppressive activity than CD4+ or CD8+ Tregs. We further demonstrated that cancer-associated fibroblast (CAF)–derived IL6, rather than TGFβ1, induced CD73+ γδTreg differentiation from paired normal breast tissues via the IL6/STAT3 pathway to produce more adenosine and become potent immunosuppressive T cells. CD73+ γδTregs could in turn promote IL6 secretion by CAFs through adenosine/A2BR/p38MAPK signaling, thereby forming an IL6–adenosine positive feedback loop. CD73+ γδTreg infiltration also impaired the tumoricidal functions of CD8+ T cells and significantly correlated with worse prognosis of patients. The data indicate that the IL6–adenosine loop between CD73+ γδTregs and CAFs is important to promote immunosuppression and tumor progression in human breast cancer, which may be critical for tumor immunotherapy.

Supplemental Figures 1-12 and Supplementary Tables 1-3

In this paper, an approach to solve the normal contact forces of viscoelastic particles with the finite element method is presented. A viscoelastic constitutive model is deduced and established for the finite element solution, where the stress tensors of the Zener-type model expressed as partial differential equations are obtained by applying the generalized Hooke’s law, and the incremental equations are further deduced with the backward difference method. An iterative matrix of the viscoelastic constitutive model that depends on the current strain, current stress and strain increment is derived; a user material subroutine is programed based on the iterative matrix to implement the viscoelastic constitutive model in the displacement-based finite element modeling. The validity of the finite element solution to the normal contact forces of elastic particles is validated with the Hertz contact force model, and that of the solution to the normal contact forces of viscoelastic particles is verified by the experimental data. The results obtained by the proposed solution agree well with those predicted by the Prony series, and the computational efficiency of this solution is higher for different values of the shear viscosity.

The tumor microenvironment induces immunosuppression via recruiting and expanding suppressive immune cells such as regulatory T cells (Treg) to promote cancer progression. In this study, we documented that tumor-infiltrating CD73+ γδTregs were the predominant Tregs in human breast cancer and exerted more potent immunosuppressive activity than CD4+ or CD8+ Tregs. We further demonstrated that cancer-associated fibroblast (CAF)–derived IL6, rather than TGFβ1, induced CD73+ γδTreg differentiation from paired normal breast tissues via the IL6/STAT3 pathway to produce more adenosine and become potent immunosuppressive T cells. CD73+ γδTregs could in turn promote IL6 secretion by CAFs through adenosine/A2BR/p38MAPK signaling, thereby forming an IL6–adenosine positive feedback loop. CD73+ γδTreg infiltration also impaired the tumoricidal functions of CD8+ T cells and significantly correlated with worse prognosis of patients. The data indicate that the IL6–adenosine loop between CD73+ γδTregs and CAFs is important to promote immunosuppression and tumor progression in human breast cancer, which may be critical for tumor immunotherapy.

The efficacy of cellular immunotherapy plus chemotherapy in treatment of gastric cancer (GC) remains inconsistent even controversial. Hence, we performed a meta-analysis to better comprehend the clinical value of cellular immunotherapy plus chemotherapy for GC patients. We searched PubMed, Embase and EBSCO databases to identify the studies evaluating the association of cellular immunotherapy plus chemotherapy and overall survival (OS) and/or disease-free survival (DFS) in patients with GC, and then combined relevant data into hazard ratios (HRs) for OS, DFS and clinicopathological features such as TNM stage, etc. with STATA 12.0. Eleven studies with 1244 patients were included in this meta-analysis. We found that cellular immunotherapy plus chemotherapy remarkably improved overall survival (OS) and diseases-free survival (DFS) as compared to the chemotherapy for GC patients. In subgroup analyses, pooled data showed that the combined therapy was significantly associated with better 3-year and 5-year survival rate, but not with 1-year survival rate of patients; the application of cellular immunotherapy based on either CIK or DC-CIK cells could enhance survival as well as NK, γδT and CIK cells-based immunotherapy. More importantly, the addition of cellular immunotherapy considerably improved OS and DFS only in patients with stage III rather than stage II. In addition, we also discovered that the combined therapy did not cause intolerable side effects to patients. Cellular immunotherapy plus chemotherapy ameliorates survival in GC, especially in patients with stage III, implicating that it is a valuable therapeutic strategy for these patients.

To reveal the structure-property relation of nanoporous graphene (NPG) membranes, molecular dynamics simulations are performed to study the mechanical properties of materials in uniaxial and biaxial tension, emphasizing the effects of neck width, relative density, pore size and shape. The structural evolution, crack initiation and propagation, brittle failure, Young’s modulus, strength, toughness, fracture strain are addressed. For all tensile cases, the crack initiates on the pore edge with high stress and preferably propagates along the zigzag directions of graphene. The NPG in biaxial tension shows higher modulus than those in uniaxial tension. Relative density tends to be the dominant characteristic parameter to determine the mechanical properties. With constrained geometries, “smaller is stronger”, and “smaller is tougher” are observed in the size effect of neck width. Pore shape affects the stress distribution and concentration, leading to varied mechanical responses. Particularly, the stress concentration in the tensile direction significantly reduces the mechanical performances. The scaling laws for the mechanical properties as functions of relative density and neck width are developed and presented for predicting the mechanical properties of NPG. The investigation further highlights the mechanical behaviors and potentially accelerates the promising applications of NPG membranes.

This paper presents a comparative investigation into behaviors of different damping terms of viscoelastic contact models, and introduces a novel damping term with dimensional reasoning analysis and by considering the effect of relaxation time of viscoelastic spheres. Behaviors of different contact models are compared in terms of predictions of non-dimensional variables, where the influence of damping parameters on behaviors of viscoelastic models is analyzed and the relationship between non-dimensional damping parameters and the coefficient of restitution is discussed. The damping parameter related to relaxation time is found to affect behaviors of the current viscoelastic contact model significantly. Viscoelastic models of different damping terms exhibit different behaviors, especially for a heavily damped case. Comparison between simulation and free fall impact test of viscoelastic balls demonstrates that the current contact model involving relaxation time fits experimental results better than other contact models.

The increased diversity of microstructure of nanoporous materials can be expected to greatly expand their functional application in more industries. By incorporating nanoporous metals into cold-welding technology, we report an approach to directly forming the nanoporous materials with various microstructure inside. Nanoporous gold (Au) with ideal bi-continuous nanoporous structures was modeled using spinodal decomposition. Understanding the mechanical properties is the primary step to improve the reliability on the operational performance of nanoporous structures. After the process of cold-welding manufacture, the well-interconnected nanoporous Au was successfully fabricated and the mechanical properties of cold-welded structures were studied. Molecular dynamic simulations on samples with ligament diameter ranging from 3.264 to 6.528 nm and relative density ranging from 0.30 to 0.45 were also carried out to study how these factors affect the assembly process. These results are believed to facilitate the bottom-up nanofabrication and nanoassembly of composite structures for better mechanical performance.

This paper presents a normal contact force approach for viscoelastic spheres of the same material based on the theory of viscoelasticity. The approach treats the normal contact force as an elastic component superposed with a dissipative component based on which to derive a reduced expression, and is numerically analyzed for the viscoelastic spheres modelled by the standard linear solid with the sinusoidal displacement history. The influences of relaxation time and viscosity upon the approach are discussed. An application of the approach with the collinear impact of viscoelastic balls is carried out and its adequacy to reality is validated by the comparison of the numerical solution against the impact experiment of Golf and Superball, to conclude that the suggested approach is applicable to build the kinematic equation describing the normal contact of viscoelastic bodies.

Integrating a polymer into the nanoporous metals (NPMs) could efficiently reduce the density change during plastic flow with better ductilization, which widens great potential applications of nanocomposites . In this work, a finite element model of stochastic bicontinuous nanoporous structure is generated for the first time. A nanocomposite material is generated by fitting a polymer into the pore space of NPMs, and the mechanical behaviors of the composite of nanoporous gold (npg) and epoxy under uniaxial compression are investigated via finite element analysis . Results show that the stress is mainly concentrated at the ligament necks rather than junctions of the npg constitute phase and the epoxy constitute phase during deformation. In analogy to npg, the Young’s modulus of npg-epoxy composite as a function of metal volume fraction displays a power-law relation and the yield stress has an approximately linear relation. It is worth noticing that the Young’s modulus and the yield stress of nanocomposite exceeds that of each of its constituent phases and are higher than the sum of two pure phases. The present study provides new insights into the mechanical behaviors of npg-epoxy composite, as well as a practical guide for designing a new class of strong and ductile nanocomposites.

BackgroundSystemic inflammatory response (SIR) plays important roles in initiation, promotion and progression of tumor. However, the prognostic role of baseline circulating platelet–to–lymphocyte ratio (PLR) (known as a marker of SIR) in human stage Ⅳ gastric cancer (GC) remains controversial. Hence, we performed this meta-analysis to assess the value of it in prognosis prediction for stage Ⅳ GC patients. MethodsWe searched PubMed, Embase and EBSCO to identify the studies and computed extracted data with STATA 12.0. ResultsA total of 2721 patients with stage Ⅳ GC from 12 published studies were incorporated into this meta-analysis. We found that elevated baseline circulating PLR was significantly associated with decreased overall survival (OS), but not with progression–free survival (PFS) in stage Ⅳ GC patients. However, in stratified analyses, high PLR was remarkably associated with worse 1-year OS, but not with 2-year, 3-year, 4-year or 5-year OS; In addition, it was considerably related with reduced 6-month PFS, but not with 1-year or 2-year PFS. Moreover, high PLR markedly correlated with peritoneal metastasis of patients. Conclusionelevated baseline circulating PLR decreased 1-year OS and 6-month PFS in stage Ⅳ GC patients, implicating that it is a valuable prognostic index for these patients and modifying the inflammatory responses may have a potential for effective treatment.

Fibroblasts are a highly heterogeneous population in tumor microenvironment. PDGFR-β+ fibroblasts, a subpopulation of activated fibroblasts, have proven to correlate with cancer progression through multiple of mechanisms including inducing angiogenesis and immune evasion. However, the prognostic role of these cells in solid tumors is still not conclusive. Herein, we carried out a meta-analysis including 24 published studies with 6752 patients searched from PubMed, Embase and EBSCO to better comprehend the value of such subpopulation in prognosis prediction for solid tumors. We noted that elevated density of intratumoral PDGFR-β+ fibroblasts was remarkably associated with worse overall survival (OS) and disease-free survival (DFS) of patients. In subgroup analyses, the data showed that PDGFR-β+ fibroblast infiltration considerably decreased OS in non-small cell lung cancer (NSCLC), breast and pancreatic cancer, and reduced DFS in breast cancer. In addition, increased number of PDGFR-β+ fibroblasts appreciably correlated with advanced TNM stage of patients. In conclusion, PDGFR-β+ fibroblast infiltration deteriorates survival in human solid tumors especially in NSCLC, breast and pancreatic cancer. Hence, they may offer a practicable prognostic biomarker and a potential therapeutic strategy for these patients.

Background Activated eosinophils have been deemed to affect carcinogenesis and tumor progression via various mechanisms in tumor microenvironment. However, the prognostic role of tumor-associated tissue eosinophilia (TATE) in human cancers remains controversial. Therefore, we conducted this meta-analysis to better comprehend the association between TATE and clinical outcomes of patients. Methods We searched PubMed, Embase and EBSCO to determine the researches assessing the association between TATE and overall survival (OS) and/or disease-free survival (DFS) in patients with cancer, then combined relevant data into hazard ratios (HRs) or odds ratio (OR) for OS, DFS and clinicopathological features including lymph node metastasis etc. with STATA 12.0. Results Twenty six researches with 6384 patients were included in this meta-analysis. We found that the presence of TATE was significantly associated with improved OS, but not with DFS in all types of cancers. In stratified analyses based on cancer types, pooled results manifested that the infiltration of eosinophils was remarkably associated with better OS in esophageal carcinoma and colorectal cancer. In addition, TATE significantly inversely correlated with lymph node metastasis, tumor stage and lymphatic invasion of cancer. Conclusion TATE promotes survival in cancer patients, suggesting that it is a valuable prognostic biomarker and clinical application of biological response modifiers or agonists promoting TATE may be the novel therapeutic strategy for patients.

Additional file 1: Figure S1. Flow chart diagram of study selection. Figure S2. Plots describing the influence of individual studies on the overall HRs for OS (A) and DFS (B) in human cancers. Figure S3. Funnel plots displayed the potential publication bias between TATE and OS (A) or DFS (B) in patients. Table S1. Characteristics of the included studies for OR analysis of clinicopathological features.

Guoming Hu,1 Kefang Zhong,1 Wei Chen,1 Shimin Wang,2 Liming Huang1 1Department of General Surgery (Breast and Thyroid Surgery), 2Department of Nephrology, Shaoxing People’s Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Zhejiang, China Background: Cancer-associated fibroblasts (CAFs) are a heterogeneous population, and different subpopulations play differential roles in tumor microenvironment. However, the prognostic role of podoplanin-positive CAFs in human lung cancer still remains controversial. Methods: Herein, we performed a meta-analysis including 12 published studies with 1,802 patients identified from PubMed and EBSCO to assess the prognostic impact of podoplanin-positive CAFs in lung cancer patients. Results: We found that podoplanin+ fibroblast infiltration significantly decreased overall survival (OS), disease-free survival (DFS), and progression-free survival in patients. In stratified analyses, podoplanin+ fibroblast infiltration was significantly associated with worse OS and DFS in both squamous cell carcinoma and adenocarcinoma of lung. In addition, high density of podoplanin-positive CAFs significantly correlated with unfavorable clinicopathological features such as lymph node metastasis, and lymphatic, vascular, and pleural invasion of patients. Conclusion: Podoplanin+ fibroblast infiltration leads to worse clinical outcome in lung cancer patients, implicating that it is a valuable prognostic biomarker and targeting it may have a potential for effective treatment. Keywords: podoplanin-positive cancer-associated fibroblasts, worse outcome, lung cancer, meta-analysis

A series of large-scale molecular dynamics (MD) simulations has been performed to study the effects of grain size and ligament diameter on the mechanical properties of nanocrystalline nanoporous gold. Such simulations indicate that the principal deformation mechanism is a combination of grain boundary sliding, grain rotation and dislocation movement. The results of uniaxial tensile tests reveal the presence of a reverse Hall-Petch relation between strength and nominal grain size, rather than the conventional Hall-Petch relationship in the present range of nominal grain size (7.9–52.7 nm). An increase of flow stress may possibly attribute to the lower total proportion of grain boundary sliding and grain rotation in the deformation of samples with larger grain size. The Young’s modulus shows a linear relation with the reciprocal of nominal grain size, which depends largely on the volume fraction of grain boundaries and thus decreasing grain size leads to relatively lower Young’s modulus. MD simulations on samples with ligament diameter ranging from 4.07 to 8.10 nm are also carried out and results show that the increasing ligament diameter resulted in decreased flow stress and increased Young’s modulus.

Purpose: Activated tumor-infiltrating fibroblasts were significantly associated with survival of cancer patients. However, they are heterogeneous population, and the prognostic role of these cells in human breast cancer still remains controversial. Herein, we performed the meta-analysis to better understand the role of these cells in prognosis prediction for breast cancer patients. Methods: We searched PubMed and EBSCO to identify the studies evaluating the association of intratumoral activated fibroblast density detected by immunohistochemical (IHC) method and overall survival (OS) and/or disease-free survival (DFS) in breast cancer patients, then computed extracted data into hazard ratios (HRs) for OS, DFS and clinicopathological features such as lymph node metastasis, TNM stage with STATA 12.0. Results: A total of 3680 patients with breast cancer from 15 published studies were incorporated into this meta-analysis. We found that the infiltration of activated fibroblasts significantly decreased overall survival (OS) and disease-free survival (DFS) in patients. In stratified analyses, high density of FSP-1+ or podoplanin+ fibroblasts was significantly associated with worse OS; while α-SMA+ or podoplanin+ fibroblast infiltration was associated with worse DFS in breast cancer. In addition, elevated number of activated tumor-infiltrating fibroblasts significantly correlated with lymph node metastasis and poor tumor differentiation of patients. Conclusion: The infiltration of activated fibroblasts, especially the FSP-1+ or podoplanin+ fibroblasts leads to worse clinical outcome in breast cancer patients, implicating that it is a valuable prognostic biomarker and targeting it may have a potential for effective treatment.

The prognostic role of tumor-infiltrating tryptase+ mast cells in human solid tumors remains controversial. Herein, we conducted a meta-analysis including 28 published studies with 4224 patients identified from PubMed and EBSCO to assess the prognostic impact of tumor-infiltrating tryptase+ mast cells in human solid tumors. We found that tryptase+ mast cell infiltration significantly decreased overall survival (OS) and disease-free survival (DFS) in all types of solid tumors. In stratified analyses, tryptase+ mast cell infiltration was significantly associated with worse OS in non-small cell lung cancer, hepatocellular carcinoma and 5-year survival in colorectal cancer. And these cells were inversely associated with DFS in hepatocellular and colorectal cancer. In addition, high density of intratumoral tryptase+ mast cells significantly correlated with lymph node metastasis of solid tumor. In conclusion, Tryptase+ mast cell infiltration leads to an unfavorable clinical outcome in solid tumors, implicating that it is a valuable biomarker for prognostic prediction for human solid malignances and targeting it may have a potential for effective treatment.

Lobular carcinoma in situ (LCIS) represents 5.3% of in situ specimens, and is thought to carry a low risk for developing to the invasive lobular breast cancer (ILC). There is still no standard care approach for patients with LCIS. We aimed to define the impacts of surgical and radiation intervention on survival outcomes of LCIS. LCIS cases from 2004 to 2013 of the recent Surveillance, Epidemiology, and End Results (SEER) database were analyzed. Clinicopathologic features were analyzed in 16002 patients between 2004 and 2013. Treatment modalities included no surgery (NS), lumpectomy alone (LA), lumpectomy with radiation treatment (LRT), mastectomy alone (MA) and mastectomy with radiation treatment (MRT). The overall survival (OS) was calculated by the Kaplan-Meier method. Univariate and multivariate analyses were performed using the variables of treatment, race, hormone receptor status, grade and age. Among 16002 patients, median follow-up was 54 months. Patients treated with LA had superior OS for NS (P = 0.001), MA (P < 0.001) and MRT P = 0.018). LRT only had superior OS for MRT (P = 0.009). There was no statistically significance between LA and LRT (P = 0.317). Improved OS was also correlated with younger age (P < 0.001), progesterone receptor positive (P = 0.001). Black patients had the worst OS (P < 0.001). There was no obvious survival difference among grade groups (P = 0.536). The LCIS patients treated with LA or LRT had better survival comparing with other groups. Considering the medical expense and the risk of radiotherapy, LA may be the most appropriate therapy for patients with LCIS.

The prognostic role of tumor-infiltrating CD45RO+ memory T lymphocytes (CD45RO+ T cells) in human solid tumors remains controversial. Herein, we conducted a meta-analysis including 25 published studies with 4720 patients identified from PubMed and EBSCO to assess the prognostic impact of tumor-infiltrating CD45RO+ T cells in human solid tumors. We found that CD45RO+ T cell infiltration was significantly associated with improved overall survival (OS) and disease-free survival (DFS) in all types of solid tumors. In stratified analyses, CD45RO+ T cell infiltration significantly improved 1-year, 3-year and 5-year OS in colorectal, gastric and esophageal cancer, but only 5-year OS in hepatocellular carcinoma. And these cells were positively associated with 1-year, 3-year and 5-year DFS in hepatocellular, colorectal and esophageal cancer. In addition, high density of intratumoral CD45RO+ T cells inversely correlated with TNM stage of solid tumor. In conclusion, CD45RO+ memory T lymphocyte infiltration leads to a favorable clinical outcome in solid tumors, implicating that it is a valuable biomarker for prognostic prediction for human solid malignances.

FoxP3+ regulatory T cells (FoxP3+ Tregs) are considered to be a key mediator in immune escape and tumor progression. However, the role of FoxP3+ Tregs in human colorectal cancer (CRC) remains controversial. Herein, we conducted a meta-analysis including 17 published studies with 3811 patients identified from PubMed and EBSCO to assess the prognostic impact of tumor-infiltrating FoxP3+ Tregs in human CRC. We found FoxP3+ Tregs infiltrating into both intraepithelium and stroma within tumor were significantly positively correlated with 1, 3, 5 and 10-year overall survival (OS), but not with 1, 3, 5-year disease-free survival (DFS) of patients. Interestingly, in stratified analyses by compartments within tumor FoxP3+ Tregs infiltrating into, FoxP3+ Tregs invading stromal compartment significantly improved 3 and 5-year OS, yet OS wasn't improved when FoxP3+ Tregs infiltrated into intraepithelium only. Furthermore, FoxP3+ Tregs invading both intraepithelium and stroma significantly inversely correlated with TNM stage of CRC. In conclusion, High density of FoxP3+ Tregs within tumor especially at stromal compartment leads to a favorable outcome in CRC, implicating FoxP3+ Tregs are one of valuable indexes for prognostic prediction in human CRC.

The synthesis of composite nanowires has recently emerged to be an important topic in the field of low-dimension nanostructures, and molecular dynamics (MD) simulation proves an effective way to figure out their mechanical properties and is thus adopted to explore the cold welding process of gold nanowires with single-crystalline, fivefold twinned and particularly polycrystalline structure. Four samples of nanowires were successfully welded through limited loadings with similar stress-time responses toward cold welding. The stress shows a low average value during welding with oscillations, indicating the existence of relaxation stages. Herein, the number of defects in the welded nanowires could be controlled by varying the loading time. These findings are expected to open an avenue towards the use of cold welding technology, including welding between materials with various properties, for the bottom-up nanofabrication and nanoassembly techniques without introducing defects.

The tumor microenvironment induces immunosuppression via recruiting and expanding suppressive immune cells such as regulatory T cells (Treg) to promote cancer progression. In this study, we documented that tumor-infiltrating CD73

Background: Activated eosinophils have been deemed to affect carcinogenesis and tumor progression via various mechanisms in tumor microenvironment. However, the prognostic role of tumor-associated tissue eosinophilia (TATE) in human cancers still remains controversial. Therefore, we performed the meta-analysis to better understand the role of TATE in prognosis prediction for cancer patients. Methods: We searched PubMed and EBSCO to identify the studies evaluating the association of TATE and overall survival (OS) and/or disease-free survival (DFS) in cancer patients, then computed extracted data into hazard ratios (HRs) for OS, DFS and clinicopathological features such as lymph node metastasis etc with STATA 12.0. Results: A total of 6125 patients from 25 published studies were incorporated into this meta-analysis. We found that the presence of TATE significantly improved OS and 5-year DFS in all types of cancers. In stratified analyses based on cancer types, pooled results indicated that eosinophils infiltrating into tumor tissue was significantly associated with better OS in oral cancer, esophageal carcinoma and colorectal cancer. In addition, TATE was significantly inversely correlated with lymph node metastasis, tumor stage and lymphatic invasion of cancer. Conclusion: TATE leads to a favorable clinical outcome in cancer patients, implicating that it is a valuable biomarker for prognostic prediction for human cancers and clinical application of biological response modifiers or agonists promoting TATE may be the novel therapeutic strategy for patients.

By using molecular dynamics simulations, we investigate the tensile response of nanoporous (NP) Cu50Zr50 metallic glasses (MGs) with 3D gyroidal structure. Similar to nanoporous crystalline metals, NP–MGs fail by the plastic necking of ligaments, but shear bandings (SBs) prevail in those thick–ligament specimens. Particularly, with ligament diameter decreasing to 2.34 nm, SBs are hardly observed due to the limit of translation from shear transformation zones, resulting in superior strength and ductility of NP–MGs. The critical ligament size to suppress the formation of SBs is much smaller than those calculated value in MGs. The observations reveal a design strategy that a concurrent high strength and ductility of MGs could be obtained by designing 3D nanoporous structure with supra–nano size. The scaling laws for Young's modulus and strength as functions of relative density and ligament diameters are addressed, consistent with those in nanoporous crystalline materials.

Using the finite element analysis, we investigate the shock response, deformation behavior and energy–absorbing characteristics of stochastic bicontinuous nanoporous gold computationally, considering the effects of impact speed and relative density of materials. Three deformation modes during shocking, quasi–static compression, transition state and dynamic compression, are observed with the increasing impact speeds and the corresponding internal deformation mechanisms are demonstrated. The shock response under low–speed loading is similar to the R–LHP–L materials model, and it is more inclined to the R–S–H model as the impact speed rises. The peak stress, plateau stress, densification strain, energy, specific energy absorption (per unit volume) are assessed quantitatively. The peak stress shows a monotonous increase with impact speed, due to the enhanced inertial effect. The plateau stress and energy–absorbing efficiency are insensitive to low impact velocity, but significantly enhanced under high–speed loading. Remarkably, the results show that the energy absorption efficiency of nanoporous gold is better than conventional foam materials and nanofluidic energy absorption and dissipation system. The research not only further clarifies the shock responses and associated mechanisms of NPG, but also promotes its industrial application as an energy–absorbing material.

Zhen Wang,1 Pin Wu,1,2 Dang Wu,1 Zhigang Zhang,3 Guoming Hu,1 Shuai Zhao,1 Yucheng Lai,1 Jian Huang1,41Cancer Institute, Key Laboratory of Cancer Prevention and Intervention, Key Laboratory of Molecular Biology in Medical Sciences, China National Ministry of Education, 2Department of Thoracic Surgery, 3Department of Gynecology, 4Department of Surgical Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of ChinaPurpose: Interleukin-6 (IL-6) plays an important role in human colorectal cancer (CRC) development. However, the exact clinical and prognostic significance of IL-6 in CRC is still unclear. Here, we conducted this meta-analysis to explore this issue in detail.Methods: A meta-analysis was performed to clarify the association between serum IL-6 expression and clinical outcomes in articles published up to June 2015. Weighted mean difference (WMD) and its corresponding 95% confidence interval (CI) were used to assess the association between serum IL-6 expression and the clinicopathological characteristics of CRC. Hazard ratio (HR) with 95% CI was used to quantify the predictive value of IL-6 on CRC prognosis.Results: Fourteen studies comprising 1,245 patients were included. Analysis of these data showed that serum IL-6 expression was highly correlated with poor 5-year overall survival (OS) rate (HR =0.43, 95% CI: 0.31–0.59, P=0.755). Simultaneously, we also found that serum IL-6 expression was associated with certain clinical parameters of CRC, such as tumor invasion (T category: T0–T2, T3–T4) (WMD =3.15, 95% CI: 1.92–4.39, P=0.816), distant metastasis (M category: M0, M1) (WMD =4.69, 95% CI: 3.33–6.06, P=0.377), and tumor stage (I–II, III–IV) (WMD =2.65, 95% CI: 1.09–4.21, P=0.066).Conclusion: A high serum IL-6 expression is associated with adverse OS in CRC. The IL-6 expression can be an important supplement in establishing prognostic score for clinical decision.Keywords: interleukin-6, colorectal cancer, prognosis, meta-analysis

An ordered bimetallic nanoporous structure might be preferable and promising for catalytic applications due to the decreased Pt loading and the enhanced stability. Understanding the mechanical behaviors is the prerequisite for enhancing and prolonging the durability performance of catalysts. Herein, nanoporous (NP) Pt–Co alloys with three–dimensional stochastic bi–continuous structures are created by simulating the spinodal evolution. Molecular dynamics (MD) simulations have been utilized to research the mechanical behaviors of structurally ordered nanoporous Pt–Co alloys ( NP - Pt 3 Co , NP - PtCo 3 and NP - PtCo ) under uniaxial tension. The mechanical properties of three tested nanoporous Pt–Co alloys are significantly enhanced compared with NP–Pt, and NP - Pt 3 Co behaves with the superior mechanical properties due to its unique atomic arrangements. The dominating plastic deformation in the ligaments of nanoporous Pt–Co alloys is the axial yielding, and materials primarily fail through plastic necking and rupture of those ligaments in the loading direction, similar to that of NP–Au. Not only the modulus but also the strength scales a linear or exponential relation with relative density. The present results will provide insights for the mechanical optimization of nanoporous alloys as well as a new design strategy for more stable catalysts. Subjectareas material science, computational material.

This paper is aimed at investigating the mechanical properties and deformation mechanisms of nanocrystalline copper under nanoindentation. The Voronoi tessellation method is adopted to generate nanocrystalline structures with stochastic grain orientations that mimic those in experiments. Grain-size effect is studied and discussed via molecular dynamics simulations. The results reveal the inversion of Hall-Petch relation about hardness at a grain size of 15.1 nm, which agrees well with previous works in tension. Below the critical grain size, grain boundary sliding, grain growth and grain rotation are easily observed. Grain boundary motion is the dominant deformation with smaller grain size below 15.1 nm while dislocation motion dominates above the critical value. It is noteworthy that the elastic recovery in indentation direction, increases with larger grain size and monocrystalline copper behaves with the strongest elastic recovery. The study further reveals the deformation mechanism of nanocrystalline copper under nanoindentation and accelerates the functional applications of nanocrystalline materials. Subject areas Material science; computational material.

Systemic inflammatory response (SIR) plays important roles in initiation, promotion and progression of tumor. However, the prognostic role of preoperative circulating neutrophil–lymphocyte ratio (NLR) (known as a marker of SIR) in human primary bladder cancer (BC) undergoing radical cystectomy (RC) remains controversial. Hence, we performed this meta-analysis to better understand the role of preoperative circulating NLR in prognosis prediction for primary BC patients undergoing RC. We searched PubMed, Embase and EBSCO to identify the studies and computed extracted data with STATA 12.0. A total of 11,945 patients with BC from 18 published studies were incorporated into this meta-analysis. We found that elevated NLR was significantly associated with decreased 3-year and 5-year overall survival (OS), 1-year, 3-year and 5-year recurrence-free survival (RFS), but not with 1-year or 10-year OS, or 10-year RFS in primary BC patients who underwent RC. The results also showed that neoadjuvant chemotherapy (NAC) had a significant impact on the negative prognostic effect of NLR. In addition, high NLR significantly correlated with unfavorable clinicopathological features of BC. Elevated preoperative circulating NLR leads to an unfavorable outcome in primary BC undergoing RC, especially in patients without NAC, implicating that it might be a valuable prognostic index for these patients.

Background/Aims: Tumor-infiltrating fibroblasts are a heterogeneous population, and different subpopulations play differential roles in tumor microenvironment. However, the prognostic role of podoplanin+ fibroblasts in human solid tumors still remains controversial. Therefore, we performed the meta-analysis to better understand the role of this subpopulation in prognosis prediction for patients with solid tumor. Methods: We searched PubMed and EBSCO to identify the studies evaluating the association of intratumoral podoplanin+ fibroblast density detected by immunohistochemical method and overall survival (OS) and/or disease-free survival (DFS) in patients with solid tumor, then computed extracted data into hazard ratios for OS, DFS and clinicopathological features with STATA 12.0. Results: A total of 4883 patients from 29 published studies were incorporated into this meta-analysis. We found that podoplanin+ fibroblast infiltration significantly decreased OS and DFS in all types of solid tumors. In stratified analyses, podoplanin+ fibroblast infiltration was significantly associated with worse OS in cholangiocarcinoma, breast, lung and pancreatic cancer. And these cells were inversely associated with DFS in breast, lung and pancreatic cancer. In addition, high density of these cells significantly correlated with unfavorable clinicopathological features such as lymph node metastasis, TNM stage, lymphatic and vascular invasion of solid tumor. Conclusion: Podoplanin+ fibroblast infiltration leads to worse clinical outcome in solid tumors, implicating that it is a valuable prognostic biomarker and targeting it may have a potential for effective treatment.

Nanoporous metals are a class of novel nanomaterials with potential applications in many fields. Herein, we demonstrate the cold-welding mechanism of nanoporous metals with various combinations using molecular dynamics simulations. This study shows that it is possible to cold-weld two nanoporous metals to form a novel composite material. The influence of temperature, in the range of 300-900 K, on the mechanical properties of the resultant composite material was investigated. With an increase in temperature, the weld stress and the mechanical strength of the nanoporous structures significantly decreased as an increase in disorder magnitude was observed. These results could lead to bottom-up nanofabrication and nanoassembly of combined nanoporous metals for high mechanical performance.

The prognostic role of tumor-infiltrating CD57-positive lymphocytes (CD57+ lymphocytes) in human solid tumors remains controversial. Herein, we conducted a meta-analysis including 26 published studies with 7656 patients identified from PubMed and EBSCO to assess the prognostic impact of tumor-infiltrating CD57+ lymphocytes in human solid tumors. We found that CD57+ lymphocyte infiltration significantly improved overall survival (OS) including 1 - year, 3 - year and 5 - year survival, and disease - free survival (DFS) in all types of solid tumors. In stratified analyses, CD57+ lymphocyte infiltration was significantly associated with better OS in hepatocellular, esophageal, head and neck carcinoma, non-small cell lung cancer, 5 - year survival in colorectal cancer, and 3 - year and 5 - year survival in gastric cancer, but not with 1 - year survival in gastric cancer, or 1 - year or 3 - year survival in colorectal cancer. In addition, high density of intratumoral CD57+ lymphocytes was significantly inversely correlated with lymph node metastasis and TNM stage of solid tumor. In conclusion, CD57+ lymphocyte infiltration leads to a favorable clinical outcome in solid tumors, implicating that it is a useful biomarker for prognosis and adoptive immunotherapy based on these cells may be a promising choice for treatment.

Breast cancer is a heterogeneous group of diseases with diverse clinicopathological and molecular features. At present, chemo-resistance still poses a major obstacle to successful treatment of HER-2 negative breast cancer. Reliable biomarkers are urgently needed to accurately predict the therapeutic sensitivity and prognosis of such patients. In this study, we identified 3145 distant relapse-free survival (DRFS) associated genes in 310 patients with HER-2 negative breast cancer receiving taxane and anthracycline-based chemotherapy in the GSE25055 dataset using univariate survival analysis. Four genes (SRPK1, PCCA, PRLR and FBP1) were further selected by a robust likelihood-based survival model. A risk score model was then constructed with the regression coefficients of the four signature genes. Patients in the training set were successfully divided into high- and low-risk groups with significant differences in DRFS between the two groups. The predictive value was further validated in GSE25065 dataset and similar results were observed. Moreover, the 4-gene signature was proved to have superior prognostic power compared with several clinical signatures such as tumor size, lymph node invasion, TNM stage and PAM50 signature. Our findings indicated that the 4-gene signature was a robust prognostic marker with a good prospect of clinical application for HER-2 negative breast cancer patients receiving taxane-anthracycline combination therapy.

The prognostic role of tumor-infiltrating tryptase