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"Yu, Jun"
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Gut microbiota in colorectal cancer development and therapy
Colorectal cancer (CRC) is one of the commonest cancers globally. A unique aspect of CRC is its intimate association with the gut microbiota, which forms an essential part of the tumour microenvironment. Research over the past decade has established that dysbiosis of gut bacteria, fungi, viruses and Archaea accompanies colorectal tumorigenesis, and these changes might be causative. Data from mechanistic studies demonstrate the ability of the gut microbiota to interact with the colonic epithelia and immune cells of the host via the release of a diverse range of metabolites, proteins and macromolecules that regulate CRC development. Preclinical and some clinical evidence also underscores the role of the gut microbiota in modifying the therapeutic responses of patients with CRC to chemotherapy and immunotherapy. Herein, we summarize our current understanding of the role of gut microbiota in CRC and outline the potential translational and clinical implications for CRC diagnosis, prevention and treatment. Emphasis is placed on how the gut microbiota could now be better harnessed by developing targeted microbial therapeutics as chemopreventive agents against colorectal tumorigenesis, as adjuvants for chemotherapy and immunotherapy to boost drug efficacy and safety, and as non-invasive biomarkers for CRC screening and patient stratification. Finally, we highlight the hurdles and potential solutions to translating our knowledge of the gut microbiota into clinical practice.Emerging data indicate a central role for the microbiota in all aspects of colorectal cancer (CRC). Despite this general consensus, understanding the role of specific components of the microbiota in such a way that enables the development of clinical interventions or tools to inform clinical decision-making has thus far proved challenging. In this Review, the authors summarize the role of the microbiota in CRC, including in prevention, in interactions with treatment and as a source of novel biomarkers.
Journal Article
Broadband Solar Metamaterial Absorbers Empowered by Transformer‐Based Deep Learning
The research of metamaterial shows great potential in the field of solar energy harvesting. In the past decade, the design of broadband solar metamaterial absorber (SMA) has attracted a surge of interest. The conventional design typically requires brute‐force optimizations with a huge sampling space of structure parameters. Very recently, deep learning (DL) has provided a promising way in metamaterial design, but its application on SMA development is barely reported due to the complicated features of broadband spectrum. Here, this work develops the DL model based on metamaterial spectrum transformer (MST) for the powerful design of high‐performance SMAs. The MST divides the optical spectrum of metamaterial into N patches, which overcomes the severe problem of overfitting in traditional DL and boosts the learning capability significantly. A flexible design tool based on free customer definition is developed to facilitate the real‐time on‐demand design of metamaterials with various optical functions. The scheme is applied to the design and fabrication of SMAs with graded‐refractive‐index nanostructures. They demonstrate the high average absorptance of 94% in a broad solar spectrum and exhibit exceptional advantages over many state‐of‐the‐art counterparts. The outdoor testing implies the high‐efficiency energy collection of about 1061 kW h m−2 from solar radiation annually. This work paves a way for the rapid smart design of SMA, and will also provide a real‐time developing tool for many other metamaterials and metadevices. This work develops the deep learning model based on metamaterial spectrum transformer (MST) for the powerful design of high‐performance solar metamaterial absorbers. The MST divides the optical spectrum of metamaterial into N patches, which overcomes the severe problem of overfitting in traditional deep learning model and boosts the learning capability significantly.
Journal Article
Gut microbiota modulation: a novel strategy for prevention and treatment of colorectal cancer
Research about the role of gut microbiome in colorectal cancer (CRC) is a newly emerging field of study. Gut microbiota modulation, with the aim to reverse established microbial dysbiosis, is a novel strategy for prevention and treatment of CRC. Different strategies including probiotics, prebiotics, postbiotics, antibiotics, and fecal microbiota transplantation (FMT) have been employed. Although these strategies show promising results, mechanistically by correcting microbiota composition, modulating innate immune system, enhancing gut barrier function, preventing pathogen colonization and exerting selective cytotoxicity against tumor cells, it should be noted that they are accompanied by risks and controversies that can potentially introduce clinical complications. During bench-to-bedside translation, evaluation of risk-and-benefit ratio, as well as patient selection, should be carefully performed. In view of the individualized host response to gut microbiome intervention, developing personalized microbiome therapy may be the key to successful clinical treatment.
Journal Article
Gut microbiota in colorectal cancer: mechanisms of action and clinical applications
Colorectal cancer (CRC) accounts for about 10% of all new cancer cases globally. Located at close proximity to the colorectal epithelium, the gut microbiota comprises a large population of microorganisms that interact with host cells to regulate many physiological processes, such as energy harvest, metabolism and immune response. Sequencing studies have revealed microbial compositional and ecological changes in patients with CRC, whereas functional studies in animal models have pinpointed the roles of several bacteria in colorectal carcinogenesis, including Fusobacterium nucleatum and certain strains of Escherichia coli and Bacteroides fragilis. These findings give new opportunities to take advantage of our knowledge on the gut microbiota for clinical applications, such as gut microbiota analysis as screening, prognostic or predictive biomarkers, or modulating microorganisms to prevent cancer, augment therapies and reduce adverse effects of treatment. This Review aims to provide an overview and discussion of the gut microbiota in colorectal neoplasia, including relevant mechanisms in microbiota-related carcinogenesis, the potential of utilizing the microbiota as CRC biomarkers, and the prospect for modulating the microbiota for CRC prevention or treatment. These scientific findings will pave the way to clinically translate the use of gut microbiota for CRC in the near future.
Journal Article
Giant energy density and high efficiency achieved in bismuth ferrite-based film capacitors via domain engineering
Developing high-performance film dielectrics for capacitive energy storage has been a great challenge for modern electrical devices. Despite good results obtained in lead titanate-based dielectrics, lead-free alternatives are strongly desirable due to environmental concerns. Here we demonstrate that giant energy densities of ~70 J cm
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, together with high efficiency as well as excellent cycling and thermal stability, can be achieved in lead-free bismuth ferrite-strontium titanate solid-solution films through domain engineering. It is revealed that the incorporation of strontium titanate transforms the ferroelectric micro-domains of bismuth ferrite into highly-dynamic polar nano-regions, resulting in a ferroelectric to relaxor-ferroelectric transition with concurrently improved energy density and efficiency. Additionally, the introduction of strontium titanate greatly improves the electrical insulation and breakdown strength of the films by suppressing the formation of oxygen vacancies. This work opens up a feasible and propagable route, i.e., domain engineering, to systematically develop new lead-free dielectrics for energy storage.
Dielectrics with high capacitive energy storage density are essential for modern electrical devices and pulsed power systems. Here, the authors realised superior energy storage performance in lead-free bismuth ferrite-based relaxor ferroelectric films through domain engineering.
Journal Article
Two-dimensional non-Hermitian skin effect in an ultracold Fermi gas
The concept of non-Hermiticity has expanded the understanding of band topology, leading to the emergence of counter-intuitive phenomena. An example is the non-Hermitian skin effect (NHSE)
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, which involves the concentration of eigenstates at the boundary. However, despite the potential insights that can be gained from high-dimensional non-Hermitian quantum systems in areas such as curved space
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, the realization of this effect in high dimensions remains unexplored. Here we create a two-dimensional (2D) non-Hermitian topological band for ultracold fermions in spin–orbit-coupled optical lattices with tunable dissipation, which exhibits the NHSE. We first experimentally demonstrate pronounced nonzero spectral winding numbers in the complex energy plane with nonzero dissipation, which establishes the existence of 2D skin effect. Furthermore, we observe the real-space dynamical signature of NHSE in real space by monitoring the centre of mass motion of atoms. Finally, we also demonstrate that a pair of exceptional points are created in the momentum space, connected by an open-ended bulk Fermi arc, in contrast to closed loops found in Hermitian systems. The associated exceptional points emerge and shift with increasing dissipation, leading to the formation of the Fermi arc. Our work sets the stage for further investigation into simulating non-Hermitian physics in high dimensions and paves the way for understanding the interplay of quantum statistics with NHSE.
A two-dimensional non-Hermitian topological band is created in an ultracold system of fermions, which exhibits the non-Hermitian skin effect.
Journal Article
The association of diet, gut microbiota and colorectal cancer: what we eat may imply what we get
Despite the success of colonoscopy screening and recent advances in cancer treatment, colorectal cancer (CRC) still remains one of the most commonly diagnosed and deadly cancers, with a significantly increased incidence in developing countries where people are adapting to Western lifestyle. Diet has an important impact on risk of CRC. Multiple epidemiological studies have suggested that excessive animal protein and fat intake, especially red meat and processed meat, could increase the risk of developing CRC while fiber could protect against colorectal tumorigenesis. Mechanisms have been investigated by animal studies.Diet could re-shape the community structure of gut microbiota and influence its function by modulating the production of metabolites. Butyrate, one of the short-chain fatty acids (SCFAs), which act as a favorable source for colonocytes, could protect colonic epithelial cells from tumorigenesis via anti-inflammatory and antineoplastic properties through cell metabolism, microbiota homeostasis, antiproliferative, immunomodulatory and genetic/epigenetic regulation ways. In contrast, protein fermentation and bile acid deconjugation, which cause damage to colonic cells through proinflammatory and proneoplastic ways, lead to increasedriskofdevelopingCRC.In conclusion, abalanced diet with an increased abundance of fiber should be adopted to reduce the risk and prevent CRC.
Journal Article
Identification of a prefrontal cortex-to-amygdala pathway for chronic stress-induced anxiety
Dysregulated prefrontal control over amygdala is engaged in the pathogenesis of psychiatric diseases including depression and anxiety disorders. Here we show that, in a rodent anxiety model induced by chronic restraint stress (CRS), the dysregulation occurs in basolateral amygdala projection neurons receiving mono-directional inputs from dorsomedial prefrontal cortex (dmPFC→BLA PNs) rather than those reciprocally connected with dmPFC (dmPFC↔BLA PNs). Specifically, CRS shifts the dmPFC-driven excitatory-inhibitory balance towards excitation in the former, but not latter population. Such specificity is preferential to connections made by dmPFC, caused by enhanced presynaptic glutamate release, and highly correlated with the increased anxiety-like behavior in stressed mice. Importantly, low-frequency optogenetic stimulation of dmPFC afferents in BLA normalizes the enhanced prefrontal glutamate release onto dmPFC→BLA PNs and lastingly attenuates CRS-induced increase of anxiety-like behavior. Our findings thus reveal a target cell-based dysregulation of mPFC-to-amygdala transmission for stress-induced anxiety.
Dysregulated prefrontal control over amygdala has been implicated in the etiology of stress-related psychiatric disorders. Here, the authors show that the dysregulation preferentially occurs in amygdala neurons that are mono- but not bi-directionally connected with dorsomedial prefrontal cortex.
Journal Article