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A Two-Step Perturbation Method in Nonlinear Analysis of Beams, Plates and Shells
The capability to predict the nonlinear response of beams, plates and shells when subjected to thermal and mechanical loads is of prime interest to structural analysis. In fact, many structures are subjected to high load levels that may result in nonlinear load-deflection relationships due to large deformations. One of the important problems deserving special attention is the study of their nonlinear response to large deflection, postbuckling and nonlinear vibration. A two-step perturbation method is firstly proposed by Shen and Zhang (1988) for postbuckling analysis of isotropic plates. This approach gives parametrical analytical expressions of the variables in the postbuckling range and has been generalized to other plate postbuckling situations. This approach is then successfully used in solving many nonlinear bending, postbuckling, and nonlinear vibration problems of composite laminated plates and shells, in particular for some difficult tasks, for example, shear deformable plates with four free edges resting on elastic foundations, contact postbuckling of laminated plates and shells, nonlinear vibration of anisotropic cylindrical shells. This approach may be found its more extensive applications in nonlinear analysis of nano-scale structures.
eBook
Applications of Inorganic Nanomaterials in Photothermal Therapy Based on Combinational Cancer Treatment
Cancer is one of the major causes of death and is difficult to cure using existing clinical therapies. Clinical cancer treatments [such as surgery, chemotherapy (CHT), radiotherapy (RT) and immunotherapy (IT)] are widely used but they have limited therapeutic effects and unavoidable side effects. Recently, the development of novel nanomaterials offers a platform for combinational therapy (meaning a combination of two or more therapeutic agents) which is a promising approach for cancer therapy. Recent studies have demonstrated several types of nanomaterials suitable for photothermal therapy (PTT) based on a near-infrared (NIR) light-responsive system. PTT possesses favorable properties such as being low in cost, and having high temporospatial control with minimal invasiveness. However, short NIR light penetration depth limits its functions.
In this review, due to their promise, we focus on inorganic nanomaterials [such as hollow mesoporous silica nanoparticles (HMSNs), tungsten sulfide quantum dots (WS
QDs), and gold nanorods (AuNRs)] combining PTT with CHT, RT or IT in one treatment, aiming to provide a comprehensive understanding of PTT-based combinational cancer therapy.
This review found much evidence for the use of inorganic nanoparticles for PTT-based combinational cancer therapy.
Under synergistic effects, inorganic nanomaterial-based combinational treatments exhibit enhanced therapeutic effects compared to PTT, CHT, RT, IT or PDT alone and should be further investigated in the cancer field.
Journal Article
Human gut microbiome impacts skeletal muscle mass via gut microbial synthesis of the short‐chain fatty acid butyrate among healthy menopausal women
Background Increasing evidence suggests that human gut microbiome plays an important role in variation of skeletal muscle mass (SMM). However, specific causal mechanistic relationship of human gut microbiome with SMM remains largely unresolved. Understanding the causal mechanistic relationship may provide a basis for novel interventions for loss of SMM. This study investigated whether human gut microbiome has a causal effect on SMM among Chinese community‐dwelling healthy menopausal women. Methods Estimated SMM was derived from whole‐body dual‐energy X‐ray absorptiometry. We performed integrated analyses on whole‐genome sequencing, shotgun metagenomic sequencing, and serum short‐chain fatty acids (SCFAs), as well as available host SMM measurements among community‐dwelling healthy menopausal women (N = 482). We combined the results with summary statistics from genome‐wide association analyses for human gut microbiome (N = 952) and SMM traits (N = 28 330). As a prerequisite for causality, we used a computational protocol that was proposed to measure correlations among gut metagenome, metabolome, and the host trait to investigate the relationship between human gut microbiome and SMM. Causal inference methods were applied to assess the potential causal effects of gut microbial features on SMM, through one‐sample and two‐sample Mendelian randomization (MR) analyses, respectively. Results In metagenomic association analyses, the increased capacity for gut microbial synthesis of the SCFA butyrate was significantly associated with serum butyrate levels [Spearman correlation coefficient (SCC) = 0.13, P = 0.02] and skeletal muscle index (SCC = 0.084, P = 0.002). Of interest was the finding that two main butyrate‐producing bacterial species were both positively associated with the increased capacity for gut microbial synthesis of butyrate [Faecalibacterium prausnitzii (SCC = 0.25, P = 6.6 × 10−7) and Butyricimonas virosa (SCC = 0.15, P = 0.001)] and for skeletal muscle index [F. prausnitzii (SCC = 0.16, P = 6.2 × 10−4) and B. virosa (SCC = 0.17, P = 2.4 × 10−4)]. One‐sample MR results showed a causal effect between gut microbial synthesis of the SCFA butyrate and appendicular lean mass (β = 0.04, 95% confidence interval 0.029 to 0.051, P = 0.003). Two‐sample MR results further confirmed the causal effect between gut microbial synthesis of the SCFA butyrate and appendicular lean mass (β = 0.06, 95% confidence interval 0 to 0.13, P = 0.06). Conclusions Our results may help the future development of novel intervention approaches for preventing or alleviating loss of SMM.
Journal Article
The politics of magic : DEFA fairy-tale films
From Paul Verhoeven's The Cold Heart in 1950 to Konrad Petzold's The Story of the Goose Princess and Her Loyal Horse Falada in 1989, East Germany's state-sponsored film company, DEFA (Deutsche Film-Aktiengesellschaft), produced over forty feature-length, live-action fairy-tale films based on nineteenth-century folk and literary tales. While many of these films were popular successes and paved the way for the studio's other films to enter the global market, DEFA's fairy-tale corpus has not been studied in its entirety. In The Politics of Magic: DEFA Fairy-Tale Films, Qinna Shen fills this gap by analyzing the films on thematic and formal levels and examining their embedded agendas in relation to the cultural politics of the German Democratic Republic.--Provided by publisher
Book
Identification and mechanism of G protein-biased ligands for chemokine receptor CCR1
Biased signaling of G protein-coupled receptors describes an ability of different ligands that preferentially activate an alternative downstream signaling pathway. In this work, we identified and characterized different N-terminal truncations of endogenous chemokine CCL15 as balanced or biased agonists targeting CCR1, and presented three cryogenic-electron microscopy structures of the CCR1–Gi complex in the ligand-free form or bound to different CCL15 truncations with a resolution of 2.6–2.9 Å, illustrating the structural basis of natural biased signaling that initiates an inflammation response. Complemented with pharmacological and computational studies, these structures revealed it was the conformational change of Tyr291 (Y2917.43) in CCR1 that triggered its polar network rearrangement in the orthosteric binding pocket and allosterically regulated the activation of β-arrestin signaling. Our structure of CCL15-bound CCR1 also exhibited a critical site for ligand binding distinct from many other chemokine–receptor complexes, providing new insights into the mode of chemokine recognition.Cryo-EM structures of the CCR1–Gi complex with N-terminal truncations of the endogenous chemokine CCL15 revealed that the conformational change of Tyr291 in CCR1 regulates β-arrestin signaling.
Journal Article
Public discourses of contemporary China : the narration of the nation in popular literatures, film, and television
\"This book explores the ways the narration of the nation in popular literatures, film, and television gives rise to various public discourses of contemporary China, and defines social subjects such as intellectuals, netizens, media elites, and state-sponsored filmmakers. It argues that these subjects have, to varying degrees, transformed the state project of modernization into their own through mass aestheticization of the nation, whereby postsocialist politics is contingent upon and performative through national aesthetics. By analyzing cultural products from a wide range of media, including the Internet, this book sheds light on the historical significance of nationalism for mass imagination and identification in the less-than-democratic system of China for the past three decades. \"-- Provided by publisher.
Book
Gasdermin-E-mediated pyroptosis drives immune checkpoint inhibitor-associated myocarditis via cGAS-STING activation
Immune checkpoint inhibitor (ICI)-induced myocarditis involves intensive immune/inflammation activation; however, its molecular basis is unclear. Here, we show that gasdermin-E (GSDME), a gasdermin family member, drives ICI-induced myocarditis. Pyroptosis mediated by GSDME, but not the canonical GSDMD, is activated in myocardial tissue of mice and cancer patients with ICI-induced myocarditis. Deficiency of GSDME in male mice alleviates ICI-induced cardiac infiltration of T cells, macrophages, and monocytes, as well as mitochondrial damage and inflammation. Restoration of GSDME expression specifically in cardiomyocytes, rather than myeloid cells, in GSDME-deficient mice reproduces ICI-induced myocarditis. Mechanistically, quantitative proteomics reveal that GSDME-dependent pyroptosis promotes cell death and mitochondrial DNA release, which in turn activates cGAS-STING signaling, triggering a robust interferon response and myocardial immune/inflammation activation. Pharmacological blockade of GSDME attenuates ICI-induced myocarditis and improves long-term survival in mice. Our findings may advance the understanding of ICI-induced myocarditis and suggest that targeting the GSDME-cGAS-STING-interferon axis may help prevent and manage ICI-associated myocarditis.
One-sentence summary
GSDME inflames ICI-associated myocarditis.
ICI-induced myocarditis is fatal, but its mechanism is unclear. Here, the authors identify GSDME as a key driver by promoting cGAS-STING signaling, enhancing our understanding of its pathogenesis.
Journal Article