The tumor premetastatic niche initiated by primary tumors is constructed by multiple molecular factors and cellular components and provides permissive condition that allows circulating tumor cells to ...successfully metastasize. Myeloid‐derived suppressor cells (MDSCs), a population of immature cells in pathological conditions, play a critical role in the formation of the premetastatic niche. However, few researches are focused on the function of monocytic MDSCs (mo‐MDSCs), a subtype of MDSCs, in the construction of the niche. Here, we show that the number of mo‐MDSCs is significantly increased in the premetastatic lungs of tumor‐bearing mice, thus promoting tumor cell arrest and metastasis. Before the arrival of tumor cells, the lung‐recruited mo‐MDSCs produced IL‐1β, thereby increasing E‐selectin expression and promoting tumor cell arrest on endothelial cells. Depletion of mo‐MDSCs in the premetastatic lungs decreased IL‐1β production, resulting in reduced E‐selectin expression. In addition, compared with alveolar macrophages and interstitial macrophages, mo‐MDSCs were the major source of IL‐1β expression in the premetastatic lungs. Cytokine array analyses and transwell experiments revealed that CCL12 recruits mo‐MDSCs to premetastatic lungs. CCL12 knockdown in tumor‐bearing mice significantly decreased mo‐MDSC infiltration into the premetastatic lungs, leading to reduced E‐selectin expression. Overall, the permissive conditions produced by the infiltrated mo‐MDSCs correlated with increased tumor cell arrest and metastasis. These results reveal a novel role of mo‐MDSCs in constructing the premetastatic niche. Thus, inhibition of mo‐MDSCs infiltration may change the premetastatic niche to normal condition and attenuate tumor metastasis.
What's new?
During premetastasis, the tissue microenvironment of distant metastatic target organs is altered to permit habitation for circulating tumor cells. Premetastatic niche formation is influenced by granulocytic myeloid‐derived suppressor cells (G‐MDSCs), but according to this study, the other major MDSC subtype, monocytic MDSCs (mo‐MDSCs), hitherto unknown factors in premetastatic niche construction, are also critical. In tumor‐bearing mice, mo‐MDSCs were greatly increased in premetastatic lung tissue, where they produced IL‐1β, thereby promoting E‐selectin expression and subsequent tumor cell adhesion to the vascular endothelium. Lung infiltration by mo‐MDSCs was significantly decreased via knockdown of chemokine (C‐C motif) ligand 12 (CCL12).
A novel double-network conductive hydrogel based on lithium acetate/gelatin/polyacrylamide (PAAM) was synthesized by heating–cooling and subsequent γ-ray radiation-induced polymerization and ...cross-linking. Owing to the hydrogen bonding interaction between lithium acetate, physical cross-linked gelatin, and chemical cross-linked PAAM, the resultant hydrogel exhibited high tensile strength (1260 kPa), high ionic conductivity (35.2 mS cm–1), notch-insensitivity (tensile strength 415 kPa, elongation at break 872% with transverse notch), and extensive strain monitoring range (0.15–800%) under optimum conditions. The lithium acetate/gelatin/polyacrylamide hydrogel strain sensor attached to the skin can sensitively monitor the subtle movements of the human body. The strain sensor based on the resultant hydrogel with transverse notch can still work for 1200 cycles, due to that the covalent-cross-linked PAAm chain bridges the cracks and stabilizes the deformation, while the physical-cross-linked gelatin was unzipped to make the blunting of notch. The conductive hydrogel with high-sensitivity and high stability is expected to be used as materials for the preparation of flexible strain sensors in the future.
Genetic sex determination by W and Z chromosomes has developed independently in different groups of organisms. To better understand the evolution of sex chromosomes and the plasticity of ...sex-determination mechanisms, we sequenced the whole genomes of a male (ZZ) and a female (ZW) half-smooth tongue sole (Cynoglossus semilaevis). In addition to insights into adaptation to a benthic lifestyle, we find that the sex chromosomes of these fish are derived from the same ancestral vertebrate protochromosome as the avian W and Z chromosomes. Notably, the same gene on the Z chromosome, dmrt1, which is the male-determining gene in birds, showed convergent evolution of features that are compatible with a similar function in tongue sole. Comparison of the relatively young tongue sole sex chromosomes with those of mammals and birds identified events that occurred during the early phase of sex-chromosome evolution. Pertinent to the current debate about heterogametic sex-chromosome decay, we find that massive gene loss occurred in the wake of sex-chromosome 'birth'.
A recent genetic linkage map was employed to detect quantitative trait loci (QTLs) associated with Vibrio anguillarum resistance in Japanese flounder. An F1 family established and challenged with V. ...anguillarum in 2009 was used for QTL mapping. Of the 221 simple sequence repeat (SSR) markers used to detect polymorphisms in the parents of F1, 170 were confirmed to be polymorphic. The average distance between the markers was 10.6 cM. Equal amounts of genomic DNA from 15 fry that died early and from 15 survivors were pooled separately to constitute susceptible bulk and resistance bulk DNA. Bulked segregant analysis and QTL mapping were combined to detect candidate SSR markers and regions associated with the disease. A genome scan identified four polymorphic SSR markers, two of which were significantly different between susceptible and resistance bulk (P = 0.008). These two markers were located in linkage group (LG) 7; therefore, all the SSR markers in LG7 were genotyped in all the challenged fry by single marker analysis. Using two different models, 11–17 SSR markers were detected with different levels of significance. To confirm the associations of these markers with the disease, composite interval mapping was employed to genotype all the challenged individuals. One and three QTLs, which explained more than 60 % of the phenotypic variance, were detected by the two models. Two of the QTLs were located at 48.6 cM. The common QTL may therefore be a major candidate region for disease resistance against V. anguillarum infection.
The tumor premetastatic niche initiated by primary tumors is constructed by multiple molecular factors and cellular components and provides permissive condition that allows circulating tumor cells to ...successfully metastasize. Myeloid-derived suppressor cells (MDSCs), a population of immature cells in pathological conditions, play a critical role in the formation of the premetastatic niche. However, few researches are focused on the function of monocytic MDSCs (mo-MDSCs), a subtype of MDSCs, in the construction of the niche. Here, we show that the number of mo-MDSCs is significantly increased in the premetastatic lungs of tumor-bearing mice, thus promoting tumor cell arrest and metastasis. Before the arrival of tumor cells, the lung-recruited mo-MDSCs produced IL-1beta, thereby increasing E-selectin expression and promoting tumor cell arrest on endothelial cells. Depletion of mo-MDSCs in the premetastatic lungs decreased IL-1beta production, resulting in reduced E-selectin expression. In addition, compared with alveolar macrophages and interstitial macrophages, mo-MDSCs were the major source of IL-1beta expression in the premetastatic lungs. Cytokine array analyses and transwell experiments revealed that CCL12 recruits mo-MDSCs to premetastatic lungs. CCL12 knockdown in tumor-bearing mice significantly decreased mo-MDSC infiltration into the premetastatic lungs, leading to reduced E-selectin expression. Overall, the permissive conditions produced by the infiltrated mo-MDSCs correlated with increased tumor cell arrest and metastasis. These results reveal a novel role of mo-MDSCs in constructing the premetastatic niche. Thus, inhibition of mo-MDSCs infiltration may change the premetastatic niche to normal condition and attenuate tumor metastasis. What's new? During premetastasis, the tissue microenvironment of distant metastatic target organs is altered to permit habitation for circulating tumor cells. Premetastatic niche formation is influenced by granulocytic myeloid-derived suppressor cells (G-MDSCs), but according to this study, the other major MDSC subtype, monocytic MDSCs (mo-MDSCs), hitherto unknown factors in premetastatic niche construction, are also critical. In tumor-bearing mice, mo-MDSCs were greatly increased in premetastatic lung tissue, where they produced IL-1beta, thereby promoting E-selectin expression and subsequent tumor cell adhesion to the vascular endothelium. Lung infiltration by mo-MDSCs was significantly decreased via knockdown of chemokine (C-C motif) ligand 12 (CCL12).
Anion-scavenging materials tailored for 99TcO4− trapping are urgently needed for both nuclear-related environmental remediation and management of spent nuclear fuel. For the first time, we report ...here an ultra-robust imidazolium-decorated covalent organic framework (COF) conjugate fabricated by an ionizing radiation strategy, for efficient capture of 99TcO4−. The charged imidazolium moieties are controllably anchored into the channel of the COF by simply adjusting the γ-ray dose, thereby leading to tunable ReO4− uptake up to 952 mg g−1 with high selectivity and fast kinetics. More importantly, the high porosity and ultra-robust nanofiber structure of the COFs make them ideal packing materials for dynamic column experiments. >99.98% ReO4−/TcO4− can be efficiently separated and re-collected, even after four adsorption-desorption cycles, ranking a new record of the elimination rate for ReO4− adsorption. The performance of these materials suggests attractive opportunities in practical applications for TcO4− removal from the environment and nuclear waste.
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•Robust imidazolium-decorated COFs were fabricated by an ionizing radiation strategy•The COFs exhibit tunable ReO4− uptake up to 952 mg g−1 with high selectivity•The COFs act as ideal packing materials for fast dynamic column separation of TcO4−
99Tc is one of the most problematic fission products in used nuclear fuel due to its high yield, radiation hazard, and high mobility of its typical species 99TcO4−. Anion-scavenging materials tailored for 99TcO4− trapping are, thus, urgently needed for both environmental remediation and management of spent nuclear fuel. Covalent organic frameworks (COFs) as a new class of porous crystalline materials represent one of the most promising adsorbents for TcO4−. Before their application, however, the rational construction of COF conjugates suitable for column tests is quite necessary but challenging.
By adopting the ionizing radiation strategy, we constructed ultra-robust imidazolium-decorated COF conjugates and achieved tunable TcO4− uptake with the emphasis on the advantages of the COFs in terms of column experiments. This work suggests attractive opportunities of the COFs in practical radionuclide separation and also contribute to solving the practical issues of MOF and COF applications.
Wang et al. report here an ultra-robust imidazolium-decorated covalent organic framework (COF) conjugate fabricated by an ionizing radiation strategy for efficient capture of 99TcO4−, where tunable ReO4− uptake up to 952 mg g−1 can be achieved by simply adjusting the γ-ray dose. The COFs feature high porosity, ultra-robust nanofiber structure, and fast adsorption kinetics, thus emphasizing their advantages in terms of column experiments.
Genetic sex determination by W and Z chromosomes has developed independently in different groups of organisms. To better understand the evolution of sex chromosomes and the plasticity of ...sex-determination mechanisms, we sequenced the whole genomes of a male (ZZ) and a female (ZW) half-smooth tongue sole (Cynoglossus semilaevis). In addition to insights into adaptation to a benthic lifestyle, we find that the sex chromosomes of these fish are derived from the same ancestral vertebrate protochromosome as the avian W and Z chromosomes. Notably, the same gene on the Z chromosome, dmrt1, which is the male-determining gene in birds, showed convergent evolution of features that are compatible with a similar function in tongue sole. Comparison of the relatively young tongue sole sex chromosomes with those of mammals and birds identified events that occurred during the early phase of sex-chromosome evolution. Pertinent to the current debate about heterogametic sex-chromosome decay, we find that massive gene loss occurred in the wake of sex-chromosome 'birth'.
Genetic sex determination by W and Z chromosomes has developed independently in different groups of organisms. To better understand the evolution of sex chromosomes and the plasticity of ...sex-determination mechanisms, we sequenced the whole genomes of a male (ZZ) and a female (ZW) half-smooth tongue sole (Cynoglossus semilaevis). In addition to insights into adaptation to a benthic lifestyle, we find that the sex chromosomes of these fish are derived from the same ancestral vertebrate protochromosome as the avian W and Z chromosomes. Notably, the same gene on the Z chromosome, dmrt1, which is the male-determining gene in birds, showed convergent evolution of features that are compatible with a similar function in tongue sole. Comparison of the relatively young tongue sole sex chromosomes with those of mammals and birds identified events that occurred during the early phase of sex-chromosome evolution. Pertinent to the current debate about heterogametic sex-chromosome decay, we find that massive gene loss occurred in the wake of sex-chromosome 'birth'.
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