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Accurate identification of single nucleotide variants (SNVs) in key driver genes holds a significant value for disease diagnosis and treatment. Fluorescent probes exhibit tremendous potential in specific, high-resolution, and rapid detection of SNVs. However, additional steps are required in most post-PCR assays to convert double-stranded DNA (dsDNA) products into single-stranded DNA (ssDNA), enabling them to possess hybridization activity to trigger subsequent reactions. This process not only prolongs the complexity of the experiment but also introduces the risk of losing target information. In this study, we proposed two strategies for enriching active double-stranded DNA, involving PCR based on obstructive groups and cleavable units. Building upon this, we explored the impact of modified units on the strand displacement reaction (SDR) and assessed their discriminatory efficacy for mutations. The results showed that detection of low variant allele frequencies (VAF) as low as 0.1% can be achieved. The proposed strategy allowed orthogonal identification of 45 clinical colorectal cancer tissue samples with 100% specificity, and the results were generally consistent with sequencing results. Compared to existing methods for enriching active targets, our approach offers a more diverse set of enrichment strategies, characterized by the advantage of being simple and fast and preserving original information to the maximum extent. The objective of this study is to offer an effective solution for the swift and facile acquisition of active double-stranded DNA. We anticipate that our work will facilitate the practical applications of SDR based on dsDNA.

Stable isotope-assisted metabolomics (SIAM) is a powerful tool for discovering transformation products (TPs) of contaminants. Nevertheless, the high cost or lack of isotope-labeled analytes limits its application. In-house H/D (hydrogen/deuterium) exchange reactions enable direct 2H labeling to target analytes with favorable reaction conditions, providing intuitive and easy-to-handle approaches for environmentally relevant laboratories to obtain cost-effective 2H-labeled contaminants of emerging concern (CECs). We first combined the use of in-house H/D exchange and 2H-SIAM to discover potential TPs of 6PPD (N-1,3-dimethylbutyl-N′-phenyl-p-phenylenediamine), providing a new strategy for finding TPs of CECs. 6PPD-d9 was obtained by in-house H/D exchange with favorable reaction conditions, and the impurities were carefully studied. Incomplete deuteride, for instance, 6PPD-d8 in this study, constitutes a major part of the impurities. Nevertheless, it has few adverse effects on the 2H-SIAM pipeline in discovering TPs of 6PPD. The 2H-SIAM pipeline annotated 9 TPs of 6PPD, and commercial standards further confirmed the annotated 6PPDQ (2-anilino-5-(4-methylpentan-2-ylamino)cyclohexa-2,5-diene-1,4-dione) and PPPD (N-phenyl-p-phenylenediamine). Additionally, a possible new formation mechanism for 6PPDQ was proposed, highlighting the performance of the strategy. In summary, this study highlighted a new strategy for discovering the TPs of CECs and broadening the application of SIAM in environmental studies.

Calcareous sand is widely present in coastal areas around the world and is usually considered as a weak and unstable material due to its high compressibility and low strength. Microbial-induced calcium carbonate precipitation (MICP) is a promising technique for soil improvement. However, the commonly adopted bio-augmented MICP approach is in general less compatible with the natural soil environment. Thus, this study focuses on the bio-stimulated MICP approach, which is likely to enhance the dominance of ureolytic bacteria for longer period and thus is deemed more efficient. The main objective of this paper is to investigate the compressibility of calcareous sand treated by bio-stimulated MICP approach. In the current study, a series of one-dimension compression tests was conducted on bio-cemented sand prepared via bio-stimulation with different initial relative densities (Dr). Based on the obtained compression curves and particle size distribution (PSD) curves, the parameters including cementation content, the coefficient of compressibility (av), PSD, relative breakage (Br), and relative agglomeration (Ar) were discussed. The results showed that avdecreased with the increasing cementation content. The bio-cemented sand prepared with higher initial Drhad smaller (approximately 20%–70%) avvalues than that with lower initial Dr. The specimen with higher initial Drand higher cementation content resulted in smaller Brbut larger Ar. Finally, a conceptual framework featuring multiple contact and damage modes was proposed.

In this study, a 3D-prinited solution-flow type microdroplet cell (SF-MDC) is employed as a new technique for the fabrication of porous anodic aluminum oxide (AAO) layer using oxalic acid electrolyte on aluminum. The surface morphology of the porous AAO film was characterized by a scanning electron microscope. The aim of this study was to fabricate a through-hole porous alumina layer in a single step anodizing process and to investigate the influence of anodized voltages and scanning speeds on the thickness and pore structure of alumina layer. The results showed that the pore diameter and interpore distance were directly proportional to the anodizing voltage. The thicknesses of formed AAO films were found to be 35.5, 50.7, and 81.6 μm at scanning speeds of 10, 5, and 2.5 μms−1, respectively. Through-hole porous AAO was successfully fabricated at room temperature without chemical etching. The SF-MDC fabrication technique is proposed as an environmentally attractive and suitable process for the fabrication of porous AAO layers.

MicroRNA (miRNA) and apurinic/apyrimidinic endonuclease 1 (APE1) have been reported to be closely associated with cancers, making them potential crucial biomarkers and therapeutic targets. However, focusing on the detection of a single target is not conducive to the diagnosis and prognosis assessment of diseases. In this study, an AND logic-gate-based dual-locking hairpin-mediated catalytic hairpin assembly (DL-CHA) was developed for sensitive and specific detection of microRNA and APE1. By addition of a lock to each of the hairpins, with APE1 and microRNA serving as keys, fluorescence signals could only be detected in the presence of simultaneous stimulation by APE1 and miRNA-224. This indicated that the biosensor could operate as an AND logic gate. DL-CHA exhibited advantages such as a low background, rapid response, and high logic capability. Therefore, the biosensor serves as a novel approach to cancer diagnosis with significant potential applications.

Additive manufacturing (AM) of micro metallic structures by traditional manufacturing techniques has several limitations. Electrochemical additive manufacturing (ECAM) is a cost-effective, environmentally friendly process and highly applicable for the fabrication of crack and void-free three-dimensional (3D) dense micro and nanosized metallic structures. Several microstructure nanomaterials have been fabricated through layer-by-layer electrochemical deposition using microdevice tips. Mask-less localized electrochemical deposition is a recently developed and non-traditional microstructure AM technology that originated from electrochemical deposition. It fabricates a 3D freestanding metallic microstructure layer by layer at an atomic level. In this review, the achievability of mask-based and mask-less electrochemical deposition as a non-thermal microstructure AM process is summarized. Additionally, the additive fabrication of different metallic microstructures metals such as the electrochemical deposition of nickel, copper, and the deposition of metal on anodic aluminum films are explained. The technical competencies and drawbacks of mask-less and mask-based electrochemical deposition are described. The influences of electrochemical deposition parameters including deposition time, current density, interelectrode gap, electrolyte pH, and temperature are broadly discussed. Moreover, this paper explains the current development and challenges of AM along with its materials and applications.

This article deals with the non-permutation flow shop scheduling problems with non-availability intervals. Specifically, two kinds of unavailability constraints are investigated and the jobs are non-resumable in both cases. In the first case, the non-availability intervals are periodically fixed and known in advance. In the second case, the intervals are flexible and the machines’ continuous working time cannot exceed a maximum allowed time. Two mixed binary integer programming models are provided for deriving the optimal schedules, respectively. The problems of minimising makespan in such flow shops are proved Non-deterministic Polynomial-time hard in strong sense. Then a hybrid incremental genetic algorithm (HIGA) that combines an incremental evolution strategy framework, a local refinement and a population diversity supervision scheme is proposed to solve the large-sized problems efficiently. The numerical experiments under different problem parameters’ settings indicate that the HIGAcan achieve quite satisfactory performance compared with genetic algorithm and a constructive heuristic based on Nawaz, Enscore, Ham.

Based on the character of upward slicing backfilling mining and the condition of Gonggeyingzi coal mine in Inner Mongolia, this paper describes the studies of the strata behavior and the stress distribution in the process of backfilling mining in extra-thick coal seams. This was achieved by setting up and analyzing the elastic foundation beam model using the ABAQUS software. The results show that: (1) With the gradual mining of different slices, the roof appears to bend continuously but does not break. The vertical stress in the roof decreases and the decreasing amplitude reduces, while the tensile stress in the roof grows with the mining slices and the maximum tensile stress will not exceed the allowable tensile stress. (2) The front vertical stress at the working face exceeds the rear vertical stress and both show a trend of decrease with decreasing amplitude of decrease. (3) The slices mined early have more influence on the surrounding rock than the later ones. Similarly, the strata behavior experiences the same trend. The field measured data show that the roof does not break during the mining process, which is consistent with the conclusion.

AbstractIn this paper, a multilevel correction scheme is proposed to solve the Steklov eigenvalue problem by nonconforming finite element methods. With this new scheme, the accuracy of eigenpair approximations can be improved after each correction step which only needs to solve a source problem on finer finite element space and an Steklov eigenvalue problem on the coarsest finite element space. This correction scheme can increase the overall efficiency of solving eigenvalue problems by the nonconforming finite element method. Furthermore, as same as the direct eigenvalue solving by nonconforming finite element methods, this multilevel correction method can also produce the lower-bound approximations of the eigenvalues.

The naturally existing diffusive flow provides revisited values for the multiple flow direction (MFD) algorithm for digital elevation models. However, since the flow is uniformly distributed over a grid cell, existing MFD algorithms can hardly force the flow to propagate within a finite region without arbitrary dispersion. In this study, an improved Triangular Form‐based Multiple Flow Algorithm called iTFM is proposed to limit the arbitrary dispersion by considering the nonuniform flow domain in a cell. In the new algorithm, flow is routed between facets rather than cells and drained to at most two downstream facets, which forces the flow to propagate over partial subregions of a cell, so that different facets in the cell may have different contributing areas. In addition, two alternative strategies including vector split (VS) and area split (AS) are evaluated to determine the flow split ratio for the two downstream facets in this study. Then, the algorithms combining different split strategies (i.e., iTFM‐VS, iTFM‐AS) are compared with eight existing algorithms over four numerical terrains and one physical terrain. The visual and quantitative assessment results show that iTFM‐AS can provide accurate total contributing areas and predicted flow domains for numerical terrains with resolutions ranging from 1 to 20 m. Moreover, the flow domains predicted by iTFM‐AS are in high agreement with the observed domains over the physical terrain with practical resolutions. Therefore, it can be concluded that the iTFM‐AS algorithm can better and more robustly define the dispersive flow domain. A new multiple flow direction algorithm adopting the triangular facet division is developed to determine the dispersive flow domainsThe flow is drained to triangular facets in the cardinal direction considering the nonuniformly‐distributed flow domain over each gridiTFM‐AS algorithm can better define the dispersive flow domain with robustness in physical terrain A new multiple flow direction algorithm adopting the triangular facet division is developed to determine the dispersive flow domains The flow is drained to triangular facets in the cardinal direction considering the nonuniformly‐distributed flow domain over each grid iTFM‐AS algorithm can better define the dispersive flow domain with robustness in physical terrain

DNA strand displacement plays an essential role in the field of dynamic DNA nanotechnology. However, flexible regulation of strand displacement remains a significant challenge. Most previous regulatory tools focused on controllable activation of toehold and thus limited the design flexibility. Here, we introduce a regulatory tool termed cooperative branch migration (CBM), through which DNA strand displacement can be controlled by regulating the complementarity of branch migration domains. CBM shows perfect compatibility with the majority of existing regulatory tools, and when combined with forked toehold, it permits continuous fine-tuning of the strand displacement rate spanning 5 orders of magnitude. CBM manifests multifunctional regulation ability, including rate fine-tuning, continuous dynamic regulation, reaction resetting, and selective activation. To exemplify the powerful function, we also constructed a nested if-function signal processing system on the basis of cascading CBM reactions. We believe that the proposed regulatory strategy would effectively enrich the DNA strand displacement toolbox and ultimately promote the construction of DNA machines of higher complexity in nucleic acid research and biomedical applications.

Coral sand is widely encountered in coastal areas of tropical and subtropical regions. Compared with silica sand, it usually exhibits weaker performance from the perspective of engineering geology. To improve the geomechanical performance of coral sand and meet the requirement of foundation construction in coastal areas, a novel alkali activation-based sustainable binder was developed. The alkali-activated slag (AAS) binder material was composed of ground granulated blast-furnace slag (GGBS) and hydrated lime with the amendment of biochar, an agricultural waste-derived material. The biochar-amended AAS stabilized coral sand was subjected to a series of laboratory tests to determine its mechanical, physicochemical, and microstructural characteristics. Results show that adding a moderate amount of biochar in AAS could improve soil strength, elastic modulus, and water holding capacity by up to 20%, 70%, and 30%, respectively. Moreover, the addition of biochar in AAS had a marginal effect on the sulfate resistance of the stabilized sand, especially at high biochar content. However, the resistance of the AAS stabilized sand to wet-dry cycles slightly deteriorated with the addition of biochar. Based on these observations, a conceptual model showing biochar-AAS-sand interactions was proposed, in which biochar served as an internal curing agent, micro-reinforcer, and mechanically weak point.

The redistribution of hillslope soil water during and after rainstorms is affected by soil properties and topography. Therefore, understanding how soil‐terrain attributes affect the soil volumetric water content (VWC) distribution under various catchment storages is a prerequisite for accurate hydrological modeling. Herein, the relationships between soil‐terrain attributes and soil VWC were examined in a steep (average slope = 60%), forested, zero‐order catchment. Detailed topography, soil properties, and runoff, and high frequency (6‐min) soil moisture data observed from July 2016 to November 2017 were employed along with resampled VWC data in three time‐steps (daily, hourly, and 6‐min intervals) for correlation analysis between soil‐terrain attributes and measured VWC. The results showed that daily aggregated data overlooked the highly heterogeneous flow conditions under dry‐wet transitions, leading to a constantly high correlation between VWC and the topographic wetness index (TWI). In comparison, the 6‐min data captured short‐lived flow processes, highlighting that, in reality, VWC‐TWI correlations fluctuated frequently as a function of catchment storages and precipitation characteristics, with four wetting patterns identified. Under wet‐dry transitions, the VWC‐TWI correlations increased significantly (from 0.3 to 0.6) as the hillslope gradually drained of lateral subsurface water. Soil water behavior consists of diurnal oscillations superimposed on a declining trend, which demonstrates the existence of unsaturated flow and which contributed to the increase in the strength of the correlations. Finally, through correlation analysis of all drying (n= 4) and wetting (n= 45) periods, we found that soil‐terrain attributes and VWC correlations can be used to identify the dominant soil water processes in various catchment storages. The soil‐terrain attributes and soil moisture correlations were influenced by storage and precipitation inputs during wetting periodsSoil water behavior consists of diurnal oscillations superimposed on a declining trend during drying periodsTopography remains important in soil water redistribution during wet‐dry transitions The soil‐terrain attributes and soil moisture correlations were influenced by storage and precipitation inputs during wetting periods Soil water behavior consists of diurnal oscillations superimposed on a declining trend during drying periods Topography remains important in soil water redistribution during wet‐dry transitions

A new eight‐direction algorithm (iFAD8) for the simulation of drainage directions on grid digital elevation models (DEMs) is presented. In this algorithm, a flexible triangular facet construction technique (ND∞) is developed to provide local drainage directions ranging continuously from 0° to 360°. Subsequently, a flow aggregation technique using global deviations of local drainage directions is proposed to simplify the flow paths into a nondispersive format. Another algorithm (FAD8) accompanying the iFAD8 is also presented, which uses the D∞ directions as the local drainage directions. Then FAD8, iFAD8, and three existing algorithms are compared on 10 abstract terrains including nine basic terrains and a Himmelblau terrain. The algorithms are tested to reproduce exact slope lines and specific catchment areas derived from the terrain functions. The results show that iFAD8 has better performance than FAD8. Both iFAD8 and FAD8 outperform existing algorithms in most cases. The flow aggregation technique is shown to be an excellent choice for nondispersive drainage direction simulation based on infinite directions. The ND∞ direction based on flexible triangular facets is also an improvement to the local infinite direction of D∞. We conclude that the iFAD8 algorithm can provide better definitions of drainage directions. Overland movement of water and soil plays an important role in hydrological cycle and geomorphologic evolution. Analysis and modeling of these processes rely on drainage direction information. Through digitalizing and discretizing a continuous terrain into a mass of grid cells, drainage direction can be assigned to each cell. The accuracy of drainage directions may have a tremendous impact on the hydrologic and geomorphologic modeling. So an advanced algorithm for determination of drainage direction is required. Many algorithms have been proposed for this purpose. But there are some shortcomings in the existing algorithms. Here we present a new algorithm named iFAD8 to provide single drainage direction for each topographic cell. Two newly developed techniques are adopted in iFAD8 to improve both local drainage directions and global flow paths. iFAD8 partly optimizes the shortcomings of existing algorithms in theory and has a better performance on various terrains. Finally, iFAD8 will benefit hydrologic and geomorphologic modeling. A new nondispersive eight‐direction algorithm to simulate drainage directions is developedThe algorithm approximates theoretical drainage directions through flexible triangular facetsA flow aggregation technique iterating global deviations of local drainage directions is purposed