A variety of fascinating morphological patterns arise on surfaces of growing, developing or aging tissues, organs and microorganism colonies. These patterns can be classified into creases, wrinkles, ...folds, period-doubles, ridges and delaminated-buckles according to their distinctive topographical characteristics. One universal mechanism for the pattern formation has been long believed to be the mismatch strains between biological layers with different expanding or shrinking rates, which induce mechanical instabilities. However, a general model that accounts for the formation and evolution of these various surface-instability patterns still does not exist. Here, we take biological structures at their current states as thermodynamic systems, treat each instability pattern as a thermodynamic phase, and construct a unified phase diagram that can quantitatively predict various types of growth-induced surface instabilities. We further validate the phase diagram with our experiments on surface instabilities induced by mismatch strains as well as the reported data on growth-induced instabilities in various biological systems. The predicted wavelengths and amplitudes of various instability patterns match well with our experimental data. It is expected that the unified phase diagram will not only advance the understanding of biological morphogenesis, but also significantly facilitate the design of new materials and structures by rationally harnessing surface instabilities.
Currently, chemotherapy remains the standard treatment for first- and second-line management of small cell lung cancer (SCLC). Immunotherapy has made progress in the treatment of SCLC, and nivolumab, ...pembrolizumab, atezolizumab, and durvalumab have led to significant improvements in clinical outcomes of SCLC. Regarding options in other classes of therapy, the cytotoxic drug lurbinectedin was granted orphan drug status based on a remarkable objective response rate of 39.3%. In addition, an increase in progression-free survival (PFS) was achieved in a phase II study of anlotinib (ALTER 1202). Future prospects for even better outcomes in SCLC lie in novel ways to integrate immunotherapy and small-molecule TKI drugs. Innovative clinical trial designs are needed to efficiently explore the increasing number of options with new drugs and new combinations thereof for SCLC.
Biological surfaces display fascinating topographic patterns such as corrugated blood cells and wrinkled dog skin. These patterns have inspired an emerging technology in materials science and ...engineering to create self-organized surface patterns by harnessing mechanical instabilities. Compared with patterns generated by conventional lithography, surface instability patterns or so-called ruga patterns are low cost, are easy to fabricate, and can be dynamically controlled by tuning various physical stimuli—offering new opportunities in materials and device engineering across multiple length scales. This article provides a systematic review on the fundamental mechanisms and innovative functions of surface instability patterns by categorizing various modes of instabilities into a quantitatively defined thermodynamic phase diagram, and by highlighting their engineering and biological applications.
Dynamic polymer networks (DPNs) crosslinked by dynamic bonds have received intensive attention because of their special crack-healing capability. Diverse DPNs have been synthesized using a number of ...dynamic bonds, including dynamic covalent bond, hydrogen bond, ionic bond, metal-ligand coordination, hydrophobic interaction, and others. Despite the promising success in the polymer synthesis, the fundamental understanding of their self-healing mechanics is still at the very beginning. Especially, a general analytical model to understand the interfacial self-healing behaviors of DPNs has not been established. Here, we develop polymer-network based analytical theories that can mechanistically model the constitutive behaviors and interfacial self-healing behaviors of DPNs. We consider that the DPN is composed of interpenetrating networks crosslinked by dynamic bonds. The network chains follow inhomogeneous chain-length distributions and the dynamic bonds obey a force-dependent chemical kinetics. During the self-healing process, we consider the polymer chains diffuse across the interface to reform the dynamic bonds, being modeled by a diffusion-reaction theory. The theories can predict the stress-stretch behaviors of original and self-healed DPNs, as well as the healing strength in a function of healing time. We show that the theoretically predicted healing behaviors can consistently match the documented experimental results of DPNs with various dynamic bonds, including dynamic covalent bonds (diarylbibenzofuranone and olefin metathesis), hydrogen bonds, and ionic bonds. We expect our model to be a powerful tool for the self-healing community to invent, design, understand, and optimize self-healing DPNs with various dynamic bonds.
Diacylglycerol (DAG) and its primary target protein kinase C (PKC) regulate many important cellular responses, yet the molecular mechanisms that control the specificity of DAG and PKC signaling are ...not fully understood. As such, targeting the PKC pathway for therapeutic purposes has been challenging. Protein kinase D (PKD), a novel DAG receptor, has been the subject of intense investigation in recent years. DAG regulates the intracellular localization of PKD and also activates PKD through PKC by phosphorylation. The PKC–PKD signaling cascade is crucial to PKD function in cells. Important discoveries have been made regarding the roles of PKD in cell growth, gene expression, survival, motility, protein trafficking and lymphocyte biology. This kinase is implicated in pathological processes such as cardiac hypertrophy, tumor cell proliferation and metastasis. Thus, PKD represents a novel therapeutic target for the DAG–PKC signaling network.
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Nanoporous BiVO4/Bi2S3 nanosheets have been firstly fabricated through a two-step annealing followed by hydrothermal method using BiOI two-dimensional nanosheets as precursors, which ...could greatly improve the photoelectrochemical performances of BiVO4 due to the enhanced charge separation efficiency and the enlarged absorption range. The optimal content of Bi2S3 in the BiVO4/Bi2S3 nanocomposites has been explored by tuning the reaction time. In addition, it is found that loading co-catalysts FeOOH could further optimize the hole transfer pathway and thus enhance the photoelectrochemical water splitting ability.
Treatment of non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) activating mutation with EGFR-TKIs has achieved great success, yet faces the development of acquired ...resistance as the major obstacle to long-term disease remission in the clinic. MET (or c-MET) gene amplification has long been known as an important resistance mechanism to first- or second-generation EGFR-TKIs in addition to the appearance of T790 M mutation. Recent preclinical and clinical studies have suggested that MET amplification and/or protein hyperactivation is likely to be a key mechanism underlying acquired resistance to third-generation EGFR-TKIs such as osimertinib as well, particularly when used as a first-line therapy. EGFR-mutant NSCLCs that have relapsed from first-generation EGFR-TKI treatment and have MET amplification and/or protein hyperactivation should be insensitive to osimertinib monotherapy. Therefore, combinatorial therapy with osimertinib and a MET or even a MEK inhibitor should be considered for these patients with resistant NSCLC carrying MET amplification and/or protein hyperactivation.
Pyroptosis: A new frontier in cancer Fang, Yuan; Tian, Shengwang; Pan, Yutian ...
Biomedicine & pharmacotherapy,
January 2020, 2020-01-00, 20200101, 2020-01-01, Volume:
121
Journal Article
Peer reviewed
Open access
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•Pyroptosis, is a hot, caspase-1/4/5/11-dependent inflammatory cell death.•Pyroptosis is also an emerging hot spot in cancer.•Pyroptosis plays a crucial role in the proliferation and ...migration of cancer regulated by molecules like non-coding RNAs.•These molecules have guiding significance in prevention and treatment of cancer.
Pyroptosis is an inflammatory form of cell death triggered by certain inflammasomes, leading to the cleavage of gasdermin D (GSDMD) and activation of inactive cytokines like IL-18 and IL-1β. Pyroptosis has been reported to be closely associated to some diseases like atherosclerosis and diabetic nephropathy. Recently, some studies found that pyroptosis can influence the proliferation, invasion and metastasis of tumor, which regulated by some non-coding RNAs and other molecules. Hence, we provided an overview of morphological and molecular characteristics of pyroptosis. We also focus on mechanism of regulating pyroptosis in tumor cells as well as the potential roles of pyroptosis in cancer to explore potential diagnostic markers in cancers contributing to the prevention and treatment in cancers.
BRAF and KRAS are two key oncogenes in the RAS/RAF/MEK/MAPK signaling pathway. Concomitant mutations in both KRAS and BRAF genes have been identified in non-small cell lung cancer (NSCLC). They lead ...to the proliferation, differentiation, and apoptosis of tumor cells by activating the RAS/RAF/MEK/ERK signaling pathway. To date, agents that target RAS/RAF/MEK/ERK signaling pathway have been investigated in NSCLC patients harboring BRAF mutations. BRAF and MEK inhibitors have gained approval for the treatment of patients with NSCLC. According to the reported findings, the combination of MEK inhibitors with chemotherapy, immune checkpoint inhibitors, epidermal growth factor receptor-tyrosine kinase inhibitors or BRAF inhibitors is highly significant for improving clinical efficacy and causing delay in the occurrence of drug resistance. This review summarized the existing experimental results and presented ongoing clinical studies as well. However, further researches need to be conducted to indicate how we can combine other drugs with MEK inhibitors to significantly increase therapeutic effects on patients with lung cancer.
Cephalopods can display dazzling patterns of colours by selectively contracting muscles to reversibly activate chromatophores--pigment-containing cells under their skins. Inspired by this novel ...colouring strategy found in nature, we design an electro-mechano-chemically responsive elastomer system that can exhibit a wide variety of fluorescent patterns under the control of electric fields. We covalently couple a stretchable elastomer with mechanochromic molecules, which emit strong fluorescent signals if sufficiently deformed. We then use electric fields to induce various patterns of large deformation on the elastomer surface, which displays versatile fluorescent patterns including lines, circles and letters on demand. Theoretical models are further constructed to predict the electrically induced fluorescent patterns and to guide the design of this class of elastomers and devices. The material and method open promising avenues for creating flexible devices in soft/wet environments that combine deformation, colorimetric and fluorescent response with topological and chemical changes in response to a single remote signal.
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