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It’s critically important to construct arbitrary inorganic features with high resolution. As an inorganic photoresist, hydrogen silsesquioxane (HSQ) has been patterned by irradiation sources with short wavelength, such as EUV and electron beam. However, the fabrication of three- dimensional nanoscale HSQ features utilizing infrared light sources is still challenging. Here, we demonstrate femtosecond laser direct writing (FsLDW) of HSQ through multi-photon absorption process. 26 nm feature size is achieved by using 780 nm fs laser, indicating super-diffraction limit photolithography of λ/30 for HSQ. HSQ microstructures by FsLDW possess nanoscale resolution, smooth surface, and thermal stability up to 600 °C. Furthermore, we perform FsLDW of HSQ to construct structural colour and Fresnel lens with desirable optical properties, thermal and chemical resistance. This study demonstrates that inorganic features can be flexibly achieved by FsLDW of HSQ, which would be prospective for fabricating micro-nano devices requiring nanoscale resolution, thermal and chemical resistance. Stereolithography has progressed over the years but resolution and feature size is still limited by the properties of materials and resins. Here, the authors demonstrate femtosecond laser direct writing of a hydrogen silsesquioxane photoresist using a 780 nm femtosecond laser demonstrating feature sizes of 26 nm.

miR‐372/373, a cluster of stem cell‐specific microRNAs transactivated by the Wnt pathway, has been reported to be dysregulated in various cancers, particularly colorectal cancer (CRC); however, the unique role of these microRNAs in cancer remains to be discovered. In the present study, we characterized the upregulation in expression of miR‐372/373 in CRC tissues from The Cancer Genome Atlas data, and then showed that overexpression of miR‐372/373 enhanced the stemness of CRC cells by enriching the CD26/CD24‐positive cell population and promoting self‐renewal, chemotherapy resistance and the invasive potential of CRC cells. To clarify the mechanism underlying microRNA‐induced stemness, we profiled 45 cell signaling pathways in CRC cells overexpressing miR‐372/373 and found that stemness‐related pathways, such as Nanog and Hedgehog, were upregulated. Instead, differentiation‐related pathways, such as NFκB, MAPK/Erk and VDR, were markedly repressed by miR‐372/373. Numerous new targets of miR‐372/373 were identified, including SPOP, VDR and SETD7, all of which are factors important for cell differentiation. Furthermore, in contrast to the increase in miR‐372/373 expression in CRC tissues, the expression levels of SPOP and VDR mRNA were significantly downregulated in these tissues, indicative of the poor differentiation status of CRC. Taken together, our findings suggest that miR‐372/373 enhance CRC cell stemness by repressing the expression of differentiation genes. These results provide new insights for understanding the function and mechanisms of stem cell‐specific microRNAs in the development of metastasis and drug resistance in CRC. The miR‐372/373 cluster can induce cancer stem cell phenotypes in colorectal cancer. Over‐expression of miR‐372/373 repress developmental pathways, including NFκB, and enhance key stemness‐related pathways, such as Nanog. A series of differentiation‐related genes, including SPOP, VDR and SETD7, were identified as targets of miR‐372/373, which were shown to be responsible for the transition from cancer cell to cancer stem‐cell phenotype.

Two independent observers made a retrospective analysis of the dermoscopic images and assessed the presence of dermoscopic features included (1) multiple blue-gray globules, (2) large blue-gray ovoid nests, (3) spoke-wheel areas, (4) maple leaf-like areas, (5) concentric structures, (6) blue-gray dots, (7) arborizing vessels, (8) superficial fine telangiectasia, (9) shiny white-red structureless areas, (10) short white streaks/chrysalis, (11) multiple small erosions, (12) ulceration, and (13) large blue-gray structureless areas. According to the literature, 98 cases of BCCs were categorized according to the size of BCC as small (<1 cm) and large (≥1 cm). BCC <1 cm BCC ≥1 cm Dermoscopic features <30.0% (n = 15) 30.0%–70.0% (n = 20) >70.0% (n = 13) Total (n = 48) <30.0% (n = 16) 30.0%–70.0% (n = 20) >70.0% (n = 14) Total (n = 50) Blue-gray globules 40.0 55.0 53.8 50.0 50.0 60.0 42.9 52.0 Blue-gray ovoid nests 26.7 55.0 76.9∗ 52.1 43.8 65.0 78.6 62.0 Maple-leaf like structure 13.3 40.0 30.8 25.0 31.3 15.0 28.6 28.0 Spoke wheel-like structures 13.3 25.0 0 14.6 25.0 5.0 0 10.0 Concentric structure 13.3 20.0 15.4 16.7 18.8 10.0 7.1 12.0 Gray-blue dot 33.3 50.0 38.5 41.7 68.8 75.0 50.0 66.0|| Arborizing vessels 40.0 45.0 46.2 43.8 31.3 80.0‡ 78.6 64.0|| SFT 53.3 10.0∗ 23.1 27.1 62.5 30.0 21.4† 38.0 Shiny white-red structureless areas 20.0 20.0 0 14.6 25.0 10.0 0 12.0 Short white streaks/chrysalis 20.0 45.0 15.4 29.2 50.0 45.0 85.7‡ 58.0§ Erosion 26.7 20.0 15.4 20.8 25.0 35.0 42.9 34.0 Ulcer 33.3 20.0 15.4 22.9 50.0 45.0 78.6‡ 56.0§ Big blue-gray structureless areas 6.7 20.0 30.8 18.8 18.8 65.0†,‡ 85.7†,‡ 56.0§ ∗P values for comparison of statistical difference with <30% pigmented group for <1 cm BCCs (P < 0.05). †The P values for comparison of statistical difference with <30% pigmented group for ≥1 cm BCCs (P < 0.05). ‡The P values for comparison of statistical difference for the same extension of pigmentation between <1 and ≥1 cm BCC (P < 0.05). §The P values for comparison of statistical difference for the total individual dermoscopy character between <1 and ≥1 cm BCC (P < 0.001). ||The P values for comparison of statistical difference for the total individual dermoscopy character between <1 and ≥1 cm BCC (P < 0.05). [...]arborizing vessels, ulceration, short white streaks/chrysalis, blue-gray dots, and large blue-gray structureless areas were statistically more frequent in the large group BCCs. [...]with the growth of the tumor, tumor size affected several dermoscopic features of pigmented and heavily pigmented BCC to different degrees.

Immunosuppressive molecules are extremely valuable prognostic biomarkers across different cancer types. However, the diversity of different immunosuppressive molecules makes it very difficult to accurately predict clinical outcomes based only on a single immunosuppressive molecule. Here, we establish a comprehensive immune scoring system (ISS GC ) based on 6 immunosuppressive ligands (NECTIN2, CEACAM1, HMGB1, SIGLEC6, CD44, and CD155) using the LASSO method to improve prognostic accuracy and provide an additional selection strategy for adjuvant chemotherapy of gastric cancer (GC). The results show that ISS GC is an independent prognostic factor and a supplement of TNM stage for GC patients, and it can improve their prognosis prediction accuracy; in addition, it can distinguish GC patients with better prognosis from those with high prognostic nutritional index score; furthermore, ISS GC can also be used as a tool to select GC patients who would benefit from adjuvant chemotherapy independent of their TNM stages, MSI status and EBV status. Expression patterns of immune checkpoints in patients with gastric cancer remain poorly characterized. Here the authors propose an immune scoring system based on the expression of six immunosuppressive ligands to improve the prognostic accuracy in gastric cancer patients and drive the selection of candidates for adjuvant chemotherapy.

In this paper we investigate the shear viscoelasticity and the hydrodynamic modes in a holographic solid model with several sets of axions that all break the translations spontaneously on boundary. Comparing with the single-axion model, the shear modulus is enhanced at high temperatures and the shear viscosity is always suppressed in the presence of additional axions. However, the different sets of axions exhibit competitive relationship in determining the shear modulus at low temperatures. Furthermore, by calculating the black hole quasi-normal modes, it is found that adding more axions only increases the amount of diffusive modes. The number of the sound modes always remains unchanged.

This protocol demonstrates how to establish primary epithelial cell cultures in vitro from healthy human tissue and human cancer samples using ROCK inhibitor and irradiated feeder cells. Historically, it has been difficult to propagate cells in vitro that are derived directly from human tumors or healthy tissue. However, in vitro preclinical models are essential tools for both the study of basic cancer biology and the promotion of translational research, including drug discovery and drug target identification. This protocol describes conditional reprogramming (CR), which involves coculture of irradiated mouse fibroblast feeder cells with normal and tumor human epithelial cells in the presence of a Rho kinase inhibitor (Y-27632). CR cells can be used for various applications, including regenerative medicine, drug sensitivity testing, gene expression profiling and xenograft studies. The method requires a pathologist to differentiate healthy tissue from tumor tissue, and basic tissue culture skills. The protocol can be used with cells derived from both fresh and cryopreserved tissue samples. As approximately 1 million cells can be generated in 7 d, the technique is directly applicable to diagnostic and predictive medicine. Moreover, the epithelial cells can be propagated indefinitely in vitro , yet retain the capacity to become fully differentiated when placed into conditions that mimic their natural environment.

Skeletal muscle differentiation is controlled by multiple cell signaling pathways, however, the JNK/MAPK signaling pathway dominating this process has not been fully elucidated. Here, we report that the JNK/MAPK pathway was significantly downregulated in the late stages of myogenesis, and in contrast to P38/MAPK pathway, it negatively regulated skeletal muscle differentiation. Based on the PAR-CLIP-seq analysis, we identified six elevated miRNAs (miR-1a-3p, miR-133a-3p, miR-133b-3p, miR-206-3p, miR-128-3p, miR-351-5p), namely myogenesis-associated miRNAs (mamiRs), negatively controlled the JNK/MAPK pathway by repressing multiple factors for the phosphorylation of the JNK/MAPK pathway, including MEKK1, MEKK2, MKK7, and c-Jun but not JNK protein itself, and as a result, expression of transcriptional factor MyoD and mamiRs were further promoted. Our study revealed a novel double-negative feedback regulatory pattern of cell-specific miRNAs by targeting phosphorylation kinase signaling cascade responsible for skeletal muscle development.

In order to assess potential associations between autism spectrum disorder (ASD) phenotype, functional GI disorders and fecal microbiota, we recruited simplex families, which had only a single ASD proband and neurotypical (NT) siblings, through the Simons Simplex Community at the Interactive Autism Network (SSC@IAN). Fecal samples and metadata related to functional GI disorders and diet were collected from ASD probands and NT siblings of ASD probands (age 7-14). Functional gastrointestinal disorders (FGID) were assessed using the parent-completed ROME III questionnaire for pediatric FGIDs, and problem behaviors were assessed using the Child Behavior Check List (CBCL). Targeted quantitative polymerase chain reaction (qPCR) assays were conducted on selected taxa implicated in ASD, including Sutterella spp., Bacteroidetes spp. and Prevotella spp. Illumina sequencing of the V1V2 and the V1V3 regions of the bacterial 16S rRNA genes from fecal DNA was performed to an average depth of 208,000 and 107,000 high-quality reads respectively. Twenty-five of 59 ASD children and 13 of 44 NT siblings met ROME III criteria for at least one FGID. Functional constipation was more prevalent in ASD (17 of 59) compared to NT siblings (6 of 44, P = 0.035). The mean CBCL scores in NT siblings with FGID, ASD children with FGID and ASD without FGID were comparably higher (58-62 vs. 44, P < 0.0001) when compared to NT children without FGID. There was no significant difference in macronutrient intake between ASD and NT siblings. There was no significant difference in ASD severity scores between ASD children with and without FGID. No significant difference in diversity or overall microbial composition was detected between ASD children with NT siblings. Exploratory analysis of the 16S rRNA sequencing data, however, identified several low abundance taxa binned at the genus level that were associated with ASD and/or first order ASD*FGID interactions (FDR <0.1).

The energy-velocity relation of a dark soliton is usually derived by its exact solution, which has been used to explain the kinetic motion of the dark soliton widely in many-body physical systems. We perform a variational method to re-derive the dispersion relation, with the consideration that the number of particles of the dark soliton could be conserved. The re-derived dispersion relation is completely different from that given by the exact dark soliton solution. The validity of these two dispersion relations is tested by observing the motion of the dark soliton when we drive impurity atoms that coupled with the soliton. The results suggest that the dispersion relation given by the exact solution usually works better than the one with particle number conservation. This motivates us to reveal that density waves (carrying particle transport) are generated during the acceleration process of a dark soliton, in addition to the previously known sound waves (only carrying energy transport). We further show that the density wave emissions of dark solitons can be inhibited by increasing the impurity atom number, which is trapped by the dark soliton through nonlinear coupling. The discussion is meaningful for investigating and understanding the kinetic motion of dark solitons in many different circumstances.

Background Phosphonates are the main components in the global phosphorus redox cycle. Little is known about phosphonate metabolism in freshwater ecosystems, although rapid consumption of phosphonates has been observed frequently. Cyanobacteria are often the dominant primary producers in freshwaters; yet, only a few strains of cyanobacteria encode phosphonate-degrading (C-P lyase) gene clusters. The phycosphere is defined as the microenvironment in which extensive phytoplankton and heterotrophic bacteria interactions occur. It has been demonstrated that phytoplankton may recruit phycospheric bacteria based on their own needs. Therefore, the establishment of a phycospheric community rich in phosphonate-degrading-bacteria likely facilitates cyanobacterial proliferation, especially in waters with scarce phosphorus. We characterized the distribution of heterotrophic phosphonate-degrading bacteria in field Microcystis bloom samples and in laboratory cyanobacteria “phycospheres” by qPCR and metagenomic analyses. The role of phosphonate-degrading phycospheric bacteria in cyanobacterial proliferation was determined through coculturing of heterotrophic bacteria with an axenic Microcystis aeruginosa strain and by metatranscriptomic analysis using field Microcystis aggregate samples . Results Abundant bacteria that carry C-P lyase clusters were identified in plankton samples from freshwater Lakes Dianchi and Taihu during Microcystis bloom periods. Metagenomic analysis of 162 non-axenic laboratory strains of cyanobacteria (consortia cultures containing heterotrophic bacteria) showed that 20% (128/647) of high-quality bins from eighty of these consortia encode intact C-P lyase clusters, with an abundance ranging up to nearly 13%. Phycospheric bacterial phosphonate catabolism genes were expressed continually across bloom seasons, as demonstrated through metatranscriptomic analysis using sixteen field Microcystis aggregate samples. Coculturing experiments revealed that although Microcystis cultures did not catabolize methylphosphonate when axenic, they demonstrated sustained growth when cocultured with phosphonate-utilizing phycospheric bacteria in medium containing methylphosphonate as the sole source of phosphorus. Conclusions The recruitment of heterotrophic phosphonate-degrading phycospheric bacteria by cyanobacteria is a hedge against phosphorus scarcity by facilitating phosphonate availability. Cyanobacterial consortia are likely primary contributors to aquatic phosphonate mineralization, thereby facilitating sustained cyanobacterial growth, and even bloom maintenance, in phosphate-deficient waters. CDjGUzfe77vQSL5wxbu5DE Video Abstract