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DNA-based neural networks are a type of DNA circuit capable of molecular pattern recognition tasks. Winner-take-all DNA networks have been developed to scale up the complexity of molecular pattern recognition with a simple molecular implementation. This simplicity was achieved by replacing negative weights in individual neurons with lateral inhibition and competition across neurons, eliminating the need for dual-rail representation. Here we introduce a new type of DNA circuit that is called loser-take-all: an output signal is ON if and only if the corresponding input has the smallest analog value among all inputs. We develop a DNA strand-displacement implementation of loser-take-all circuits that is cascadable without dual-rail representation, maintaining the simplicity desired for scalability. We characterize the impact of effective signal concentrations and reaction rates on the circuit performance, and derive solutions for compensating undesired signal loss and rate differences. Using these approaches, we successfully demonstrate a three-input loser-take-all circuit with nine unique input combinations. Complementary to winner-take-all, loser-take-all DNA circuits could be used for recognition of molecular patterns based on their least similarities to a set of memories, allowing classification decisions for patterns that are extremely noisy. Moreover, the design principle of loser-take-all could be more generally applied in other DNA circuit implementations including k-winner-take-all.

Gastric cancer is one of the most common malignancies worldwide and vasculogenic mimicry (VM) is considered to be the leading cause for the failure of anti-angiogenesis therapy in advanced gastric cancer patients. In the present study, we investigate the role of tenascin-c (TNC) in the formation of VM in gastric cancer and found that TNC was upregulated in gastric cancer tissue than in the corresponding adjacent tissues and correlated with VM and poor prognosis of gastric cancer. Furthermore, knockdown of TNC significantly inhibited VM formation and proliferation of gastric cancer cells in vitro and in vivo, with a reduction in cell migration and invasion. Mechanistically, TNC knockdown suppressed the phosphorylation of ERK and subsequently inhibited the process of EMT, both of which play an important role in VM formation. Our results indicated that TNC plays an important role in VM formation in gastric cancer. Combining inhibition of TNC and ERK may be a potential therapeutic approach to inhibit gastric cancer growth and metastasis and decrease antiangiogenic therapeutic resistance.

Molecular circuits capable of processing temporal information are essential for complex decision making in response to both the presence and history of a molecular environment. A particular type of temporal information that has been recognized to be important is the relative timing of signals. Here we demonstrate the strategy of temporal memory combined with logic computation in DNA strand-displacement circuits capable of making decisions based on specific combinations of inputs as well as their relative timing. The circuit encodes the timing information on inputs in a set of memory strands, which allows for the construction of logic gates that act on current and historical signals. We show that mismatches can be employed to reduce the complexity of circuit design and that shortening specific toeholds can be useful for improving the robustness of circuit behavior. We also show that a detailed model can provide critical insights for guiding certain aspects of experimental investigations that an abstract model cannot. We envision that the design principles explored in this study can be generalized to more complex temporal logic circuits and incorporated into other types of circuit architectures, including DNA-based neural networks, enabling the implementation of timing-dependent learning rules and opening up new opportunities for embedding intelligent behaviors into artificial molecular machines.

A Gram-positive, cellulose-degrading actinobacterium, designed strain NEAU-YM18T, was isolated from rhizosphere soil of wheat (Triticum aestivum L.) sampled in Langfang, Hebei Province, PR China. The novel strain was characterized using a polyphasic approach. Morphological and chemotaxonomic characteristics confirmed that strain NEAU-YM18T belonged to the genus Catellatospora . Cells of strain NEAU-YM18T were observed to contain meso- and 3-hydroxy-diaminopimelic acids as diagnostic cell-wall amino acids. The acyl type of the cell-wall muramic acid was glycolyl. The whole-cell hydrolysates were xylose, glucose and ribose. The phospholipids consisted of diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylinositol. The major fatty acids were iso-C15 : 0, iso-C16 : 0, C18 : 1 ω9c and summed feature 5 (anteiso-C18 : 0/C18 : 2 ω6,9c). The menaquinones were MK-9(H4), MK-9(H6) and MK-9(H2). The DNA G+C content was 71.1 %. The results of 16S rRNA gene sequence and phylogenetic analyses indicated that strain NEAU-YM18T was closely related to Catellatospora chokoriensis 2-25(1)T (98.4 % 16S rRNA gene sequence similarity), Catellatospora vulcania NEAU-JM1T (98.3%) and Catellatospora sichuanensis H14505T (98.3 %) and formed a branch with C. sichuanensis H14505T. Furthermore, the whole genome phylogeny of strain NEAU-YM18T showed that the strain formed an independent clade. The digital DNA–DNA hybridization results between NEAU-YM18T and C. chokoriensis 2-25(1)T, C. vulcania NEAU-JM1T and C. sichuanensis H14505T were 25.0, 24.7 and 24.7 %, respectively, and the whole-genome average nucleotide identity values between them were 81.5, 81.4 and 81.4 %, respectively. These genetic results and some phenotypic characteristics could distinguish strain NEAU-YM18T from its reference strains. In addition, genomic analysis confirmed that strain NEAU-YM18T had the potential to decompose cellulose and produce bioactive compounds. Therefore, strain NEAU-YM18T represents a novel species of the genus Catellatospora , for which the name Catellatospora tritici sp. nov. is proposed. The type strain is NEAU-YM18T (=CCTCC AA 2020040T=JCM 33977T).

A novel cellulase-producing actinobacterium, designated strain NEAU-L178T, was isolated from soil sample collected from Qiqihaer, Heilongjiang Province, PR China. A polyphasic study was carried out to determine the taxonomic status of the strain. On the basis of 16S rRNA gene sequence analysis, strain NEAU-L178T should be classified into the genus Nonomuraea and is closely related to Nonomuraea cavernae SYSU K10005T (99.31 % 16S rRNA gene sequence similarity), Nonomuraea glycinis NEAU-BB2C19T (98.75 %), Nonomuraea guangzhouensis NEAU-ZJ3T (98.75 %) and ‘Nonomuraea rhizosphaerae’ NEAU-mq18T (98.34 %). The digital DNA–DNA hybridization values between them are 27.1, 26.1, 42.0 and 30.9 %, and the whole-genome average nucleotide identity values between them are 83.1, 82.3, 90.3 and 85.8 %, respectively. The whole-cell hydrolysates contained glucose, ribose, arabinose and madurose. The menaquinones were identified as MK-9(H0), MK-9(H4) and MK-9(H2). The major fatty acids were C16 : 0, iso-C17 : 0 and C17 : 0 10-methyl. The detected polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, hydroxy-phosphatidylethanolamine, phosphatidylinositol and three unidentified phospholipids. The genomic DNA G+C content was 69.7 mol%. In addition, whole-genome analysis indicated that strain NEAU-L178T had the potential to degrade cellulose. Based on the phenotypic, genotypic, chemotaxonomic and phylogenetic data, strain NEAU-L178T can be differentiated from its close phylogenetic relatives and represents a novel species of the genus Nonomuraea , for which the name Nonomuraea aurantiaca sp. nov. is proposed. The type strain is NEAU-L178T (=JCM 34799T=CGMCC 4.7741T).

A novel actinobacterium, designated strain NEAU-7082T, was isolated from rhizosphere soil of wheat (Triticum aestivum L.) and characterized by using a polyphasic approach. Morphological and chemotaxonomic characteristics confirmed the affiliation of strain NEAU-7082T to the genus Glycomyces . 16S rRNA gene sequence analysis indicated that strain NEAU-7082T belonged to the genus Glycomyces and was closely related to Glycomyces mayteni JCM 16217T (99.0 % 16S rRNA gene sequence similarity), Glycomyces sambucus DSM 45047T (98.4 %), Glycomyces scopariae DSM 44968T (98.3 %), Glycomyces paridis DSM 102295T (98.1 %), Glycomyces artemisiae NBRC 109773T (98.0 %) and Glycomyces dulcitolivorans DSM 105121T (97.9 %). Phylogenetic analysis using the 16S rRNA gene sequence showed that the strain formed a stable clade with G. mayteni JCM 16217T and clustered with G. sambucus DSM 45047T, G. scopariae DSM 44968T, G. artemisiae NBRC 109773T and G. dulcitolivorans DSM 105121T in the genus Glycomyces . The cell wall contained meso-diaminopimelic acid and the whole-cell hydrolysates were glucose and xylose. The polar lipid profile consisted of diphosphatidylglycerol (DPG), phosphatidylglycerol (PG), glycolipid (GL), phosphatidylinositol mannoside (PIM) and an unidentified lipid (UL). The menaquinones were MK-11(H4), MK-11 and MK-10. Major fatty acids were anteiso-C15 : 0, iso-C16 : 0 and anteiso-C17 : 0. These chemotaxonomic data substantiated the affiliation of strain NEAU-7082T to the genus Glycomyces . The DNA G+C content was 71.3 mol%. A combination of DNA–DNA hybridization results and some phenotypic characteristics demonstrated that strain NEAU-7082T could be distinguished from its closest relatives. Therefore, strain NEAU-7082T is considered to represent a novel species of the genus Glycomyces , for which the name Glycomyces albidus sp. nov. is proposed. The type strain is NEAU-7082T (=CCTCC AA 2019045T=JCM 33458T).

Developmental self-assembly of DNA nanostructures provides an ideal platform for studying the power and programmability of kinetically controlled structural growth in engineered molecular systems. Triggered initiation and designated sequencing of assembly and disassembly steps have been demonstrated in structures with branches and loops. Here we introduce a new strategy for selectively activating distinct subroutines in a developmental self-assembly program, allowing structures with distinct properties to be created in response to various molecular signals. We demonstrate this strategy in triggered self-assembly of a DNA ring, the size and growth direction of which are responsive to a key molecule. We articulate that reversible assembly steps with slow kinetics at appropriate locations in a reaction pathway could enable multiple populations of structures with stimulus-responsive properties to be simultaneously created in one developmental program. These results open up a broad design space for the self-assembly of molecules with adaptive behaviors toward advanced control in synthetic materials and molecular motors.

Radiotherapy is a common treatment for lung cancer. However, radiation pneumonitis caused by radiotherapy can affect the quality of life and prognosis of lung cancer patients. miR-513a-3p has been found to sensitize human lung adenocarcinoma cells to chemotherapy by targeting glutathione S-transferase P1 (GSTP1). Here, we found that x-ray induced the apoptosis of BEAS-2B and miR-513a-3p expression in a dose- and time-dependent manner, and miR-513a-3p-mimic significantly increased x-ray induced apoptosis, while miR-513a-3p-inhibitor significantly decreased x-ray induced apoptosis. Dual luciferase gene reporter system showed that miR-513a-3p targeted to inhibit the expression of GSTP1 in BEAS-2B cells. Moreover, knockdown of GSTP1 significantly increased, while overexpression of GSTP1 decreased the apoptosis of BEAS-2B induced by x-ray. Importantly, overexpression of GSTP1 significantly reduced miR-513a-3p-mimic elevated x-ray -induced apoptosis in BEAS-2B cells. In conclusion, x-ray caused increased expression of miR-513a-3p, and miR-513a-3p promoted x-ray-induced apoptosis of human lung cells by inhibiting GSTP1.

On the basis of the existing test data of high temperature mechanical properties of 1860 grade steel strands, a regression model of high temperature performance of steel strands that can be used for theoretical analysis and numerical calculation is obtained. Based on the non-stationary temperature field model in the fire of tall and large space buildings, the non-linear finite element numerical analysis method considering the time integral effect is used to establish the fire resistance numerical model of the large-span prestressed steel structure. Through the fire-resistance calculation example of Beam String Structure, the influence of different fire source positions on the fire-resistance of prestressed steel structures is discussed.

DNA catalysts are fundamental building blocks for diverse molecular information-processing circuits. Allosteric control of DNA catalysts has been developed to activate desired catalytic pathways at desired times. Here we introduce a new type of DNA catalyst that we call a cooperative catalyst: a pair of reversible reactions are employed to drive a catalytic cycle in which two signal species, which can be interpreted as an activator and an input, both exhibit catalytic behavior for output production. We demonstrate the role of a dissociation toehold in controlling the kinetics of the reaction pathway and the significance of a wobble base pair in promoting the robustness of the activator. We show near-complete output production with input and activator concentrations that are 0.1 times the gate concentration. The system involves just a double-stranded gate species and a single-stranded fuel species, as simple as the seesaw DNA catalyst, which has no allosteric control. The simplicity and modularity of the design make the cooperative DNA catalyst an exciting addition to strand-displacement motifs for general-purpose computation and dynamics.

A novel actinobacterium, designated strain NEAU-THZ27T, was isolated from soil collected from the Cornel peak in Jiaozuo, Henan Province, PR China and characterized using a polyphasic approach. Morphological and chemotaxonomic characteristics of the strain coincided with those of members of the genus Kribbella . The results of 16S rRNA gene sequence analysis showed that strain NEAU-THZ27T belongs to the genus Kribbella and was most closely related to Kribbella podocarpi YPL1T (98.96 %), Kribbella karoonensis Q41T (98.89 %), Kribbella aluminosa HKI 0478T (98.86%) and Kribbella hippodromi S1.4T (98.85 %), similarities to other type strains of species of the genus Kribbella were found to be less than 98.7 %. Phylogenetic analyses using the 16S rRNA gene sequence and multilocus sequence analysis using the concatenated gene sequences of the gyrB, rpoB, recA, relA and atpD genes all showed that the strain formed a separate branch in the genus Kribbella . The cell wall contained ll-diaminopimelic acid as the major diamino acid and the whole-cell hydrolysates were ribose and glucose. The major polar lipids were diphosphatidylglycerol, phosphatidylcholine, phosphatidylglycerol and phosphatidylinositol. The predominant menaquinone was MK-9(H4). Major fatty acids were iso-C16 : 0, iso-C14 : 0 and anteiso-C15 : 0, these chemotaxonomic data supported the affiliation of strain NEAU-THZ27T to the genus Kribbella . The DNA G+C content was 68.0 mol%. Furthermore, the strain could be clearly distinguished by concatenated gene genetic distances, the combination of DNA–DNA hybridization results and some phenotypic characteristics. Therefore, it is proposed that strain NEAU-THZ27T represents a novel species of the genus Kribbella , for which the name Kribbella jiaozuonensis sp. nov. is proposed. The type strain is NEAU-THZ27T (=CGMCC 4.7504T=DSM 105535T).

A Gram-positive, aerobic, non-motile, non-spore-forming, short rod-shaped strain, NEAU-LLCT, was isolated from cow dung in Shangzhi city, Heilongjiang Province, northeast China and identified by a polyphasic taxonomic study. Colonies was light yellow, round, with entire margin. Strain NEAU-LLCT was grown at 15–45℃ and pH 6.0–10.0. NaCl concentration ranged from 0 to 5% (W/V). The 16S rRNA gene sequence of NEAU-LLCT showed the high similarities with Microbacterium kyungheense JCM 18735T (98.5%), Microbacterium trichothecenolyticum JCM 1358T (98.3%) and Microbacterium jejuense JCM 18734T (98.2%). The whole-cell sugars were glucose, rhamnose, and ribose. The menaquinones contained MK-12 and MK-13. Ornithine, glutamic acid, lysine, and a small amount of alanine and glycine were the amino acids in the hydrolyzed products of the cell wall. The major fatty acids were iso-C16:0, iso-C18:0, anteiso-C15:0 and anteiso-C17:0. The main polar lipids were diphosphatidylglycerol, phosphatidylglycerol and an unidentified glycolipid. The genome of NEAU-LLCT was 4,369,375 bp and G + C content is 70.28 mol%. A combination of DNA-DNA hybridization result and some phenotypic characteristics demonstrated that strain NEAU-LLCT could be distinguished from its closely related strains. Therefore, the strain NEAU-LLCT was considered to represent a novel specie and was named Microbacterium helvum sp. (Type strain NEAU-LLCT =CCTCC AA 2018026T = JCM 32661T).

DNA origami tilings provide methods for creating complex molecular patterns and shapes using flat DNA origami structures as building blocks. Square tiles have been developed to construct micrometer-scale arrays and to generate patterns using stochastic or deterministic strategies. Here we show triangular tiles as a complementary approach for enriching the design space of DNA tilings and for extending the shape of the self-assembled arrays from 2D to 3D. We introduce a computational approach for maximizing binding specificity in a fully symmetric tile design, with which we construct a 20-tile structure resembling a rhombic triacontahedron. We demonstrate controlled transition between 3D and 2D structures using simple methods including tile concentration, magnesium, and fold symmetry in tile edge design. Using these approaches, we construct 2D arrays with unbounded and designed sizes. The programmability of the edge design and the flexibility of the structure make the triangular DNA origami tile an ideal building block for complex self-assembly and reconfiguration in artificial molecular machines and fabricated nanodevices.

From bacteria following simple chemical gradients to the brain distinguishing complex odour information, the ability to recognize molecular patterns is essential for biological organisms. This type of information-processing function has been implemented using DNA-based neural networks, but has been limited to the recognition of a set of no more than four patterns, each composed of four distinct DNA molecules. Winner-take-all computation has been suggested as a potential strategy for enhancing the capability of DNA-based neural networks. Compared to the linear-threshold circuits and Hopfield networks used previously, winner-take-all circuits are computationally more powerful, allow simpler molecular implementation and are not constrained by the number of patterns and their complexity, so both a large number of simple patterns and a small number of complex patterns can be recognized. Here we report a systematic implementation of winner-take-all neural networks based on DNA-strand-displacement reactions. We use a previously developed seesaw DNA gate motif, extended to include a simple and robust component that facilitates the cooperative hybridization that is involved in the process of selecting a ‘winner’. We show that with this extended seesaw motif DNA-based neural networks can classify patterns into up to nine categories. Each of these patterns consists of 20 distinct DNA molecules chosen from the set of 100 that represents the 100 bits in 10 × 10 patterns, with the 20 DNA molecules selected tracing one of the handwritten digits ‘1’ to ‘9’. The network successfully classified test patterns with up to 30 of the 100 bits flipped relative to the digit patterns ‘remembered’ during training, suggesting that molecular circuits can robustly accomplish the sophisticated task of classifying highly complex and noisy information on the basis of similarity to a memory.