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Tumor-resident intracellular microbiota is an emerging tumor component that has been documented for a variety of cancer types with unclear biological functions. Here, we explored the functional significance of these intratumor bacteria, primarily using a murine spontaneous breast-tumor model MMTV-PyMT. We found that depletion of intratumor bacteria significantly reduced lung metastasis without affecting primary tumor growth. During metastatic colonization, intratumor bacteria carried by circulating tumor cells promoted host-cell survival by enhancing resistance to fluid shear stress by reorganizing actin cytoskeleton. We further showed that intratumor administration of selected bacteria strains isolated from tumor-resident microbiota promoted metastasis in two murine tumor models with significantly different levels of metastasis potential. Our findings suggest that tumor-resident microbiota, albeit at low biomass, play an important role in promoting cancer metastasis, intervention of which might therefore be worth exploring for advancing oncology care.
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Neoplasias de la Mama , Microbiota , Metástasis de la Neoplasia , Animales , Neoplasias de la Mama/microbiología , Neoplasias de la Mama/patología , Línea Celular Tumoral , Femenino , Humanos , Neoplasias Pulmonares/patología , Ratones , Células Neoplásicas Circulantes/patologíaRESUMEN
Rationally modulating the binding strength of reaction intermediates on surface sites of copper-based catalysts could facilitate C-C coupling to generate multicarbon products in an electrochemical CO2 reduction reaction. Herein, theoretical calculations reveal that cascade Ag-Cu dual sites could synergistically increase local CO coverage and lower the kinetic barrier for CO protonation, leading to enhanced asymmetric C-C coupling to generate C2H4. As a proof of concept, the Cu3N-Ag nanocubes (NCs) with Ag located in partial Cu sites and a Cu3N unit center are successfully synthesized. The Faraday efficiency and partial current density of C2H4 over Cu3N-Ag NCs are 7.8 and 9.0 times those of Cu3N NCs, respectively. In situ spectroscopies combined with theoretical calculations confirm that Ag sites produce CO and Cu sites promote asymmetric C-C coupling to *COCHO, significantly enhancing the generation of C2H4. Our work provides new insights into the cascade catalysis strategy at the atomic scale for boosting CO2 to multicarbon products.
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The search for highly active and selective catalysts with high precious metal atom utilization efficiency has attracted increasing interest in both the fundamental synthesis of materials and important industrial reactions. Here, we report the synthesis of Pd-Cu nanocubes with a Cu core and an ordered B2 intermetallic CuPd shell with controllable atomic layers on the surface (denoted as Cu/B2 CuPd), which can efficiently and robustly catalyze the selective hydrogenation of acetylene (C2H2) to ethylene (C2H4) under mild conditions. The optimized Cu/B2 CuPd with a Pd loading of 9.5 at. % exhibited outstanding performance in the C2H2 semi-hydrogenation with 100% C2H2 conversion and 95.2% C2H4 selectivity at 90 °C. We attributed this outstanding performance to the core/shell structure with a high surface density of active Pd sites isolated by Cu in the B2 intermetallic matrix, representing a structural motif of single-atom alloys (SAAs) on the surface. The combined experimental and computational studies further revealed that the electronic states of Pd and Cu are modulated by SAAs from the synergistic effect between Pd and Cu, leading to enhanced performance compared with pristine Pd and Cu catalysts. This study provides a new synthetic methodology for making single-atom catalysts with high precious metal atom utilization efficiency, enabling simultaneous tuning of both geometric and electronic structures of Pd active sites for enhanced catalysis.
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In-depth investigation of metal-metal oxide interactions and their corresponding evolution is of paramount importance to heterogeneous catalysis as it allows the understanding and maneuvering of the structure of catalytic motifs. Herein, using a series of core/shell metal/iron oxide (M/FeOx, M = Pd, Pt, Au) nanoparticles and through a combination of in situ and ex situ electron and X-ray investigations, we revealed anomalous and dissimilar M-FeOx interactions among different systems under reducing conditions. Pd interacts strongly with FeOx after high-temperature reductive treatment, featured by the formation of Pd single atoms in the FeOx matrix and increased Pd-Fe bonding, while Pt transforms into ordered PtFe intermetallics and Pt single atoms immediately upon the coating of FeOx. In contrast, Au does not manifest strong bonding with FeOx. As a proof of concept of tailoring metal-metal oxide interactions for catalysis, optimized Pd/FeOx demonstrates 100% conversion and 86.5% selectivity at 60 °C for acetylene semihydrogenation.
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BACKGROUND: Sterol-regulatory element binding protein 1 (SREBP1), an intracellular cholesterol sensor located in the endoplasmic reticulum, regulates the intracellular cholesterol by the Insig-Srebp-Scap pathway. Over-expression of SREBP1 can cause dyslipidemia. SREBP1 can regulate the metabolic pathway, and then promote the proliferation of tumor cells. However, there is no relevant research of metastasis and invasion in the field of colorectal cancer (CRC). METHODS: Expression of SREBP1 was manipulated in CRC cell lines with low and high level SREBP1 expression by transfectiong with plasmids containing the SREBP1 gene, or by shRNA. The effect of SREBP1 on cell migration was assayed. The expression of SREBP1, p65 and MMP7 were detected by western blot. Human umbilical vein endothelial cell was used for detection of angiogenesis by adding the culture supernatant from HT29 and SW620. The level of reactive oxygen species (ROS) was detected by Dihydroethidium (DHE) staining. NF-κB inhibitor SN50 was used to test the relationship of SREBP1, NF-κB pathway and MMP7. RESULTS: We found that the expression of SREBP1 in colon adenocarcinoma was significantly higher than that in noncancerous tissues, especially in the invasive tumor front including tumor budding. In vitro, SREBP1 over-expressed in colon cancer cell lines HT29 promoted angiogenesis in endothelial cells, increased ROS levels, phosphorylation of NF-κB-p65 and increases MMP7 expression. The effect of SREBP1 on expression of MMP7 was lost following treatment with the NF-κB inhibitor SN50. CONCLUSION: Our results suggest that SREBP1 can promote the invasion and metastasis of CRC cells by means of promoting the expression of MMP7 related to phosphorylation of p65.
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Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Regulación Neoplásica de la Expresión Génica , Metaloproteinasa 7 de la Matriz/genética , FN-kappa B/metabolismo , Transducción de Señal , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética , Adulto , Anciano , Línea Celular Tumoral , Movimiento Celular , Neoplasias Colorrectales/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Neovascularización Patológica/genética , Neovascularización Patológica/metabolismo , Fosforilación , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Two-dimensional (2D) van der Waals materials are increasingly seen as potential catalysts due to their unique structures and unmatched properties. However, achieving precise synthesis of these remarkable materials and regulating their atomic and electronic structures at the most fundamental level to enhance their catalytic performance remain a significant challenge. In this study, we synthesized single-crystal bulk PtTe crystals via chemical vapor transport and subsequently produced atomically thin, large PtTe nanosheets (NSs) through electrochemical cathode intercalation. These NSs are characterized by a significant presence of Te vacancy pairs, leading to undercoordinated Pt atoms on their basal planes. Experimental and theoretical studies together reveal that Te vacancy pairs effectively optimize and enhance the electronic properties (such as charge distribution, density of states near the Fermi level, and d-band center) of the resultant undercoordinated Pt atoms. This optimization results in a significantly higher percentage of dangling O-H water, a decreased energy barrier for water dissociation, and an increased binding affinity of these Pt atoms to active hydrogen intermediates. Consequently, PtTe NSs featuring exposed and undercoordinated Pt atoms demonstrate outstanding electrocatalytic activity in hydrogen evolution reactions, significantly surpassing the performance of standard commercial Pt/C catalysts.
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The structure engineering of metal-organic frameworks (MOFs) forms the cornerstone of their applications. Nonetheless, realizing the simultaneous versatile structure engineering of MOFs remains a significant challenge. Herein, a dynamically mediated synthesis strategy to simultaneously engineer the crystal structure, defect structure, and nanostructure of MOFs is proposed. These include amorphous Zr-ODB nanoparticles, crystalline Zr-ODB-hz (ODB = 4,4'-oxalyldibenzoate, hz = hydrazine) nanosheets, and defective d-Zr-ODB-hz nanosheets. Aberration-corrected scanning transmission electron microscopy combined with low-dose high-angle annular dark-field imaging technique vividly portrays these engineered structures. Concurrently, the introduced hydrazine moieties confer self-reduction properties to the respective MOF structures, allowing the in situ installation of catalytic Pd nanoparticles. Remarkably, in the hydrogenation of vanillin-like biomass derivatives, Pd/Zr-ODB-hz yields partially hydrogenated alcohols as the primary products, whereas Pd/d-Zr-ODB-hz exclusively produces fully hydrogenated alkanes. Density functional theory calculations, coupled with experimental evidence, uncover the catalytic selectivity switch triggered by the change in structure type. The proposed strategy of versatile structure engineering of MOFs introduces an innovative pathway for the development of high-performance MOF-based catalysts for various reactions.
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Cancer metastasis is the leading cause of mortality in patients with cancer. Theories have been developed to explain the causes and principles of metastasis. Metastasis is attributed to cancer cell-intrinsic properties and the extrinsic cellular environment. In recent years, the intratumor microbiota has been identified as an integral tumor component and may functionally regulate various aspects of metastasis. These novel discoveries in intratumor microbiota reshape the framework of our understanding of metastasis and reveal a new path for studies on cancer progression and clinical cancer management. Here, we summarize recent advances in the emerging roles of intratumor microbiota in cancer metastasis and discuss the challenges and implications for cancer treatment.
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Microbiota , Neoplasias , Humanos , Neoplasias/microbiología , Neoplasias/patología , Metástasis de la NeoplasiaRESUMEN
Spin-orbit torque (SOT)-induced switching of perpendicular magnetization in the absence of magnetic field is crucial for the application of SOT-based spintronic devices. Recent works have demonstrated that the low-symmetry crystal structure in CuPt/CoPt can give rise to an out-of-plane (OOP) spin torque and lead to deterministic magnetization switching without an external field. However, it is essential to improve OOP effective field for the efficient switching. In this work, the impact of interface oxidation on the generation of OOP effective field in a CuPt/ferromagnet heterostructure is systematically studied. By introducing an oxidized CuPt surface, it is found that the field-free switching performance shows remarkable improvement. OOP effective field measurement indicates that the oxidation treatment can enhance the OOP effective field by more than two times. It is also demonstrated that this oxidation-induced OOP SOT efficiency enhancement is independent of the device shapes, magnetic materials, or magnetization easy axis. This work contributes to improve the performance of SOT devices and provides an effective fabrication guidance for future spintronic devices that utilize OOP SOT.
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The aerobic oxidation of alcohols and aldehydes over supported heterogeneous catalysts can be considered as comprising two complementary and linked processes: dehydrogenation and oxygen reduction. Significant rate enhancements can be observed when these processes are catalyzed by independent active sites, coupled by electron transport between the two catalysts. This effect, termed cooperative redox enhancement (CORE), could significantly influence how researchers approach catalyst design, but a greater understanding of the factors which influence it is required. Herein, we demonstrate that the Au/Pd ratio used in physical mixtures of monometallic catalysts and phase-separated Au and Pd bimetallic catalysts dramatically influences the degree to which CORE effects can promote alcohol oxidation. Perhaps more interestingly, the roles of Au and Pd in this coupled system are determined to be interchangeable. Preliminarily, we hypothesize that this is attributed to the relative rates of the coupled reactions and demonstrate how physical properties can influence this. This deeper understanding of the factors which influence CORE is an important development in bimetallic catalysis.
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Due to its inversion-broken triple helix structure and the nature of Weyl semiconductor, 2D Tellurene (2D Te) is promising to possess a strong nonlinear optical response in the infrared region, which is rarely reported in 2D materials. Here, a giant nonlinear infrared response induced by large Berry curvature dipole (BCD) is demonstrated in the Weyl semiconductor 2D Te. Ultrahigh second-harmonic generation response is acquired from 2D Te with a large second-order nonlinear optical susceptibility (χ(2) ), which is up to 23.3 times higher than that of monolayer MoS2 in the range of 700-1500 nm. Notably, distinct from other 2D nonlinear semiconductors, χ(2) of 2D Te increases extraordinarily with increasing wavelength and reaches up to 5.58 nm V-1 at ≈2300 nm, which is the best infrared performance among the reported 2D nonlinear materials. Large χ(2) of 2D Te also enables the high-intensity sum-frequency generation with an ultralow continuous-wave (CW) pump power. Theoretical calculations reveal that the exceptional performance is attributed to the presence of large BCD located at the Weyl points of 2D Te. These results unravel a new linkage between Weyl semiconductor and strong optical nonlinear responses, rendering 2D Te a competitive candidate for highly efficient nonlinear 2D semiconductors in the infrared region.
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The recent COVID-19 virus has led to a rising interest in antimicrobial and antiviral coatings for frequently touched surfaces in public and healthcare settings. Such coatings may have the ability to kill a variety of microorganisms and bio-structures and reduce the risk of virus transmission. This paper proposes an extremely rapid method to introduce rare-earth doping nano-ZnO in polyamines for the preparation of the anti-microbial polyurea coatings. The nano-ZnO is prepared by wet chemical method, and the RE-doped nano-ZnO was obtained by mixing nano ZnO and RE-dopants with an appropriate amount of nitric acid. This rapidly fabricated polyurea coating can effectively reduce bacteria from enriching on the surface. Comparing with pure nano-ZnO group, all the polyurea coatings with four different rare-earth elements (La, Ce, Pr and Gd) doped nano-ZnO. The La-doped nano-ZnO formula group indicates the highest bactericidal rate over 85% to Escherichia coli (E. coli) and Pseudomonas aeruginosa (Pseudomonas). Followed by Ce/ZnO, the bactericidal rate may still remain as high as 83% at room temperature after 25-min UV-exposure. It is believed that the RE-doping process may greatly improve the photocatalytic response to UV light as well as environmental temperature due to its thermal catalytic enhancement. Through the surface characterizations and bioassays, the coatings have a durably high bactericidal rate even after repeated usage. As polyurea coating itself has high mechanical strength and adhesive force with most substrate materials without peel-off found, this rapid preparation method will also provide good prospects in practical applications.
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Antiinfecciosos , COVID-19 , Óxido de Zinc , Antiinfecciosos/farmacología , Escherichia coli , Humanos , Polímeros , SARS-CoV-2 , Óxido de Zinc/química , Óxido de Zinc/farmacologíaRESUMEN
The tissue-resident microbiota is an integral component of multiple tumor types, but it remains challenging to characterize its abundance and composition due to its low biomass. Here, we describe an optimized protocol for quantification and profiling of tissue-resident microbiota. The major optimized steps include DNA extraction, qPCR, 16S library construction, and bioinformatics analysis. This protocol enables robust and accurate characterization of the dynamics of normal and tumor tissue-resident microbiota at its physiological abundance from both mouse and human origins. For complete details on the use and execution of this protocol, please refer to Fu et al. (2022).
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Microbiota , Neoplasias , Humanos , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Biología ComputacionalRESUMEN
All-electric switching of perpendicular magnetization is a prerequisite for the integration of fast, high-density, and low-power magnetic memories and magnetic logic devices into electric circuits. To date, the field-free spin-orbit torque (SOT) switching of perpendicular magnetization has been observed in SOT bilayer and trilayer systems through various asymmetric designs, which mainly aim to break the mirror symmetry. Here, we report that the perpendicular magnetization of CoxPt100-x single layers within a special composition range (20 < x < 56) can be deterministically switched by electrical current in the absence of external magnetic field. Specifically, the Co30Pt70 shows the largest out-of-plane effective field efficiency and best switching performance. We demonstrate that this unique property arises from the cooperation of two structural mechanisms: the low crystal symmetry property at the Co platelet/Pt interfaces and the composition gradient along the thickness direction. Compared with that in bilayers or trilayers, the field-free switching in CoxPt100-x single layer greatly simplifies the SOT structure and avoids additional asymmetric designs.
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BACKGROUND: Escherichia coli are mostly commensals but also contain pathogenic lineages. It is largely unclear whether the commensal E. coli as the potential origins of pathogenic lineages may consist of monophyletic or polyphyletic populations, elucidation of which is expected to lead to novel insights into the associations of E. coli diversity with human health and diseases. METHODS: Using genomic sequencing and pulsed field gel electrophoresis (PFGE) techniques, we analyzed E. coli from the intestinal microbiota of three groups of healthy individuals, including preschool children, university students, and seniors of a longevity village, as well as colorectal cancer (CRC) patients, to probe the commensal E. coli populations for their diversity. RESULTS: We delineated the 2280 fresh E. coli isolates from 185 subjects into distinct genome types (genotypes) by PFGE. The genomic diversity of the sampled E. coli populations was so high that a given subject may have multiple genotypes of E. coli, with the general diversity within a host going up from preschool children through university students to seniors. Compared to the healthy subjects, the CRC patients had the lowest diversity level among their E. coli isolates. Notably, E. coli isolates from CRC patients could suppress the growth of E. coli bacteria isolated from healthy controls under nutrient-limited culture conditions. CONCLUSIONS: The coexistence of multiple E. coli lineages in a host may help create and maintain a microbial environment that is beneficial to the host. As such, the low diversity of E. coli bacteria may be associated with unhealthy microenvironment in the intestine and hence facilitate the pathogenesis of diseases such as CRC.
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Neoplasias Colorrectales/patología , ADN Bacteriano/análisis , Infecciones por Escherichia coli/complicaciones , Escherichia coli/clasificación , Escherichia coli/genética , Variación Genética , Adolescente , Adulto , Anciano , Niño , Preescolar , China/epidemiología , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/microbiología , ADN Bacteriano/genética , Infecciones por Escherichia coli/microbiología , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Filogenia , Microambiente Tumoral , Adulto JovenRESUMEN
Achieving controllable coherent and incoherent light sources is crucial to meet the requests of the constantly developing integrated optics, which, however, remains challenging for the existing semiconductor materials and techniques. All-inorganic lead halide perovskites (ILHPs) are emerging as the promising semiconductors, featuring the defect-tolerant nature and tunable band gap. Herein, an experimental design, based on the interaction between ILHPs and energetic ions, for achieving controllable light emitters and microlasers is reported. We reveal that the photoluminescence intensity from ILHPs can be modulated by more than 1 order of magnitude upon low-dose gallium ion (â¼1015 ions/cm2) irradiation, which can be attributed to the generation of vacancy/interstitial defects, metallic lead, and crystal-to-amorphization transition. Such ion-dependent light emission can be exploited to make the colorful photopatterns and in situ tailor the lasing behavior from CsPbBr3 microplates. Further, a strong sputtering effect is observed with the increase of the ion dose (â¼1017 ions/cm2), which enables the top-down fabrication of microlasers based on ILHPs. These findings represent a significant step toward controllable light sources leveraging on perovskite-ion interactions.
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BACKGROUND: The role of lipid metabolism played in cancer cell growth attracts more attention. SREBP1 is a common lipid regulatory factor. It has been reported that SREBP1 can promote tumor cell resistance. The aim of this study was to investigate its role in chemoresistance of colorectal cancer (CRC). METHODS: The expression of SREBP1 in CRC tissues was analyzed by immunohistochemistry. Using a viability assay, the sensitivity to 5-fluorouracil in two colon cancer cell lines (HT-29 and SW620) was measured and its correlation with different expression levels of SREBP1 protein by western blot was investigated. RESULTS: The protein expression of SREBP1 in CRC tissues was higher than that in normal colon tissues. We found that over-expression of SREBP1 through SREBP1 gene transfection enhances the resistant of CRC cell lines to 5-FU, and SREBP1 silencing through SREBP1 shRNA transfection can promote apoptosis in 5-FU treated SW620 cells. Further study indicated that SREBP1 could inhibit the expression of caspase7 and reduce PARP1 cleavage fragments. CONCLUSION: Our results suggest that SREBP1 protect the 5-FU treated CRC cells through caspase7 dependent PARP1 cleavage in apoptosis pathway and potentially provide a new target in the treatment of CRC.
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OBJECTIVES: Vancomycin resistance in Enterococcus spp., mediated mainly by the vanA resistance gene, has become a major health concern as it has spread worldwide. Therefore, a rapid method is urgently required to detect the vanA gene for timely and appropriate antimicrobial control of resistant Enterococcus infections. METHODS: The loop-mediated isothermal amplification (LAMP) assay was optimised for vanA detection in Enterococcus spp. isolates. RESULTS: The LAMP primer set designed in this study could reliably recognise seven distinct regions of the vanA gene and amplify the gene within 25min at an isothermal temperature of 65°C with high specificity. The sensitivity of the optimised assay was high, with a detection limit for vanA as low as 100pg/µL, which is 100-fold more sensitive than the PCR assay. A special advantage of this optimised LAMP method is that the vanA gene could be detected directly from clinical specimens. CONCLUSION: This optimised LAMP assay has great application potential for efficient detection of vanA in clinical diagnosis and epidemiological studies.
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Antibacterianos/farmacología , Proteínas Bacterianas/genética , Ligasas de Carbono-Oxígeno/genética , Enterococcus faecalis/efectos de los fármacos , Enterococcus faecalis/genética , Enterococcus faecium/efectos de los fármacos , Enterococcus faecium/genética , Técnicas de Amplificación de Ácido Nucleico , Adolescente , Adulto , Enterococcus faecalis/aislamiento & purificación , Enterococcus faecium/aislamiento & purificación , Femenino , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Sensibilidad y Especificidad , Temperatura , Resistencia a la Vancomicina/genética , Adulto JovenRESUMEN
Cancer as a large group of complex diseases is believed to result from the interactions of numerous genetic and environmental factors but may develop in people without any known genetic or environmental risks, suggesting the existence of other powerful factors to influence the carcinogenesis process. Much attention has been focused recently on particular members of the intestinal microbiota for their potential roles in promoting carcinogenesis. Here we report the identification and characterization of intestinal bacteria that exhibited potent anti-malignancy activities on a broad range of solid cancers and leukemia. We collected fecal specimens from healthy individuals of different age groups (preschool children and university students), inspected their effects on cancer cells, and obtained bacteria with potent anti-malignancy activities. The bacteria mostly belonged to Actinobacteria but also included lineages of other phyla such as Proteobacteria and Firmicutes. In animal cancer models, sterile culture supernatant from the bacteria highly effectively inhibited tumor growth. Remarkably, intra-tumor administration of the bacterial products prevented metastasis and even cleared cancer cells at remote locations from the tumor site. This work demonstrates the prevalent existence of potent malignancy-killers in the human intestinal microbiota, which may routinely clear malignant cells from the body before they form cancers.