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Background: Different Traditional Chinese medicine (TCM) constitution types have different disease susceptibility and tendency, and TCM constitution identification is of great significance in TCM clinical practice. The TCM constitution identification method based on observation and consultation is subjective, and the objective identification technique opens up a new way to modernize TCM treatment. Our study aimed to build a TCM constitution identification model based on tongue feature data and machine learning algorithms, which provides a new fast and accurate method for TCM constitution identification.Methods: We use TFDA-1 tongue diagnostic instrument to collect standardized tongue images of people with Yang deficiency constitution, Yin deficiency constitution and balanced constitution. and use tongue image analysis software (TDAS) to quantitatively analyze tongue color, tongue texture and tongue coating area. Pearson correlation analysis was used to explore the correlation between tongue characteristics and TCM constitution. Four machine learning algorithms, including SVM, decision tree, random forest, and XGboost were used to build a TCM constitution identification model based on tongue features and evaluate the model's effectiveness.Results: The results show that XGboost has the highest accuracy rate among the four machine learning algorithms and the best performance in model evaluation. Pearson correlation analysis found a specific correlation between TCM constitution and tongue features. Significant correlations existed between the Yang deficiency constitution, Yin deficiency constitution, and the balanced constitution with 16 tongue features. In addition, the model's accuracy for the group 2 containing 16 tongue features was higher than that of the whole feature group (Group 1). XGboost was the most effective in this study for identifying TCM constitution, and the tongue features filtered by correlation analysis led to higher accuracy of TCM constitution identification.Conclusions: Tongue feature information can be an essential reference for TCM constitution identification. Machine learning provides a method for rapid identification of TCM constitution types. The XGboost TCM constitution identification model with good performance gives a new way for clinical " Identifying TCM Constitution by Tongue Image" implementation offers a reference and contributes to the performance of " Preventive Treatment of Disease" of TCM and individualized diagnosis and treatment and health preservation. In addition, Objective identification technology has opened up a new way to modernize TCM diagnosis and treatment.

BACKGROUND In previous studies, researchers only evaluated the scores and grades of TCM clinical randomized controlled works of literature from an overall level, which gave us a general understanding of the overall literature level. OBJECTIVE This study aims to establish a literature quality assessment system specialized for randomized controlled trial (RCT) literature in traditional Chinese medicine (TCM). METHODS We combined the general international standard and characteristics of TCM to form a checklist of literature content to be evaluated in terms of basic method information and intervention operations. Then, we established a literature information rating system to classify the focused contents into four categories in terms of varied degree of completeness and accuracy. RESULTS Based on this system, we systematically assessed the quality of 2,776 RCTs in six categories of diseases in TCM. For the basic method information in these RCTs, “outcome indicators” and “participants’ medical sources” were mentioned in most of cases, but they might be described in a vague way, with accurate rates of 60.73% and 74.52% among the cases mentioned these information; “TCM diagnosis and diagnostic basis”, “TCM syndromes”, “randomization methods”, and “blinding” were often missing, with missing rates ranging from 68.58% to 97.48%. For the intervention information in these RCTs, the complete and accurate information for the “treatment group intervention” was higher at 97.83%, compared to 82.68% for the “control group intervention”. Most of the inaccurate information occurred when only the name of an intervention operation or drug was given, but the operation’s specific contents or drug’s composition were not clearly expressed. CONCLUSIONS Our results suggested a serious concern that TCM-related concepts were often missing in trail designs for TCM RCTs, which might impede the development of TCM theories. Also, inaccurate trail designs and intervention descriptions indicated in this study can serve as negative examples for future RCT protocols or reports in TCM to avoid.

AimThe aim of this study was to assess the clinical efficacy and safety of Tripterygium-derived glycosides (TG) after 3-month and 6-month of treatments of diabetic nephropathy (DN) and to resolve the conflict between medicine guidance and clinical practice for TG application.MethodsWe conducted a systematic review and meta-analysis of randomized controlled trials involving TG application in treating DN. We extensively searched PubMed, Cochrane Library, CNKI, VIP, Wan-Fang, CBM, Chinese Clinical Trial Registry, and WHO International Clinical Trial Registration Platform till November 2020, along with grey literature for diabetes and all other relevant publications to gather eligible studies. Based on the preset inclusion and exclusion criteria, document screening, quality assessment of methodology, and data extraction was conducted by two researchers independently. The methodological quality was assessed by the Cochrane risk test from the Cochrane Handbook 5.2, and then analyses were performed by Review Manager 5.3 (Rev Man 5.3). The quality of output evidence was classified by GRADE.ResultsThirty-one eligible studies (2764 patients) were included for this meta-analysis. Our study results showed a comparable significant decrease in the 24 h-UTP and blood creatinine levels in DN patients from both 3-month and 6-month TG treatment groups, compared with the routine symptomatic treatment alone. To the contrary of the findings from the included studies, our results showed that the occurrence of serious adverse reaction events was significantly higher in the TG treated group with 6 months of treatment duration compared to that of 3 months of the treatment course. However, the total AR ratio was slightly varied while increasing the percent of severe adverse events. GRADE assessment indicated that the quality of evidence investigating TG-induced adverse reactions was moderate and that for 24 h-UTP and blood creatinine indicators were considerably low.ConclusionCombinatorial treatment regimen including TG can significantly decrease the pathological indicators for DN progression, while it can also simultaneously predispose the patient to a higher risk for developing severe adverse events, as the medicine guidance indicates. Notably, even in 3-month of course duration smaller percent of severe adverse events can get to a fatal high percent and is likely to increase proportionally as the TG treatment continues. This suggests that TG-mediated DN treatment duration should be optimized to even less than 3 continuous months to avoid adverse event onset-associated further medical complications in DN patients. In clinical practice, serious attention should be paid to these severe side-effects even in a course normally considered safe, and importantly more high-quality studies are urgently warranted to obtain detailed insights into the balance between the efficacy and safety profiles of TG application in treating DN.

Molecular knots represent one of the most extraordinary topological structures in biological polymers. Creating highly knotted nanostructures with well-defined and sophisticated geometries and topologies remains challenging. Here, we demonstrate a general strategy to design and construct highly knotted nucleic acid nanostructures, each weaved from a single-stranded DNA or RNA chain by hierarchical folding in a prescribed order. Sets of DNA and RNA knots of two- or three-dimensional shapes have been designed and constructed (ranging from 1700 to 7500 nucleotides), and they exhibit complex topological features, with high crossing numbers (from 9 up to 57). These single-stranded DNA/RNA knots can be replicated and amplified enzymatically in vitro and in vivo. This work establishes a general platform for constructing nucleic acid nanostructures with complex molecular topologies., Designing nucleic acid-based nanostructures with knots remains challenging. Here the authors present a general strategy to design and construct highly knotted 2D and 3D nanostructures from single-stranded DNA or RNA

Structural DNA nanotechnology combines branched DNA junctions with sticky-ended cohesion to create self-assembling macromolecular architectures. One of the key goals of structural DNA nanotechnology is to construct three-dimensional (3D) crystalline lattices. Here we present a new DNA motif and a strategy that has led to the assembly of a 3D lattice. We have determined the X-ray crystal structures of two related constructs to 3.1 Å resolution using bromine-derivatized crystals. The motif we used employs a five-nucleotide repeating sequence that weaves through a series of two-turn DNA duplexes. The duplexes are tied into a layered structure that is organized and dictated by a concert of four-arm junctions; these in turn assemble into continuous arrays facilitated by sequence-specific sticky-ended cohesion. The 3D X-ray structure of these DNA crystals holds promise for the design of new structural motifs to create programmable 3D DNA lattices with atomic spatial resolution. The two arrays differ by the use of four or six repeats of the five-nucleotide units in the repeating but statistically disordered central strand. In addition, we report a 2D rhombuslike array formed from similar components.

INTRODUCTION Self-folding of an information-carrying polymer into a compact particle with defined structure and function (for example, folding of a polypeptide into a protein) is foundational to biology and offers attractive potential as a synthetic strategy. Over the past three decades, nucleic acids have been used to create a variety of complex nanoscale shapes and devices. In particular, multiple DNA strands have been designed to self-assemble into user-specified structures, with or without the help of a long scaffold strand. In recent years, RNA has also emerged as a unique, programmable material, offering distinct advantages for molecular self-assembly. On the other hand, biological macromolecules, such as proteins (or protein domains), typically fold from a single polymer into a well-defined compact structure. The ability to fold de novo designed nucleic acid nanostructures in a similar manner would enable unimolecular folding instead of multistrand assembly and even replication of such structures. However, a general strategy to construct large [>1000 nucleotides (nt)] single-stranded origami (ssOrigami) remains to be demonstrated where a single-stranded nucleic acid folds into a user-specified shape. RATIONALE The key challenge for constructing a compact single-stranded structure is to achieve structural complexity, programmability, and generality while maintaining the topological simplicity of strand routing (to avoid putative kinetic traps imposed by knots) and hence ensuring smooth folding. The key innovation of our study is to use partially complemented double-stranded DNA or RNA and parallel crossover cohesion to construct such a structurally complex yet knot-free structure that can be folded smoothly from a single strand. RESULTS Here, we demonstrate a framework to design and synthesize a single DNA or RNA strand to efficiently self-fold into an unknotted compact ssOrigami structure that approximates an arbitrary user-prescribed target shape. The generality of the method was validated by the construction of 18 multikilobase DNA and 5 RNA ssOrigami, including a ~10,000-nt DNA structure (37 times larger than the previous largest discrete single-stranded DNA nanostructure) and a ~6000-nt RNA structure (10 times larger than the previous largest RNA structure). The raster-filling nature of ssOrigami permitted the experimental construction of programmable patterns of markers (for example, a “smiley” face) and cargoes on its surface, its single-strandedness enabled the demonstration of facile replication of the strand in vitro and in living cells, and its programmability allowed us to codify the design process and develop a web-based automated design tool. CONCLUSION The work here establishes that unimolecular DNA or RNA folding, similar to multicomponent self-assembly, is a fundamental, general, and practically tractable strategy for constructing user-specified and replicable nucleic acid nanostructures, and expands the design space and material scalability for bottom-up nanotechnology.

Since the origin of DNA nanotechnology over 30 years ago, branched DNA tiles have been developed to construct a variety of DNA nanostructures. Among the unique building blocks that have been demonstrated, rigid, antiparallel double-crossover (DX) tiles have had great significance as both the unit motif in the first two-dimensional DNA crystal reported and as the basic repeating unit in most DNA origami structures. In contrast, parallel DX tiles have yet to be developed, despite that they were initially reported more than 20 years ago, most likely because their assembly yields are not comparable to anti-parallel DX tiles. Herein we demonstrate construction of DNA origami architectures based on modified parallel DX tiles, in which a single-crossover linkage, rather than reciprocal crossovers, is present at each junction point between neighboring helices. The yields of these novel origami structures are similar to their counterparts that are constructed based on antiparallel DX tile units containing double-reciprocal crossovers at each junction point. We demonstrate that a unidirectional arrangement of the scaffold strand can be used in the assembly of a variety of 2D and 3D DNA origami. This new design will greatly expand the diversity of DNA origami achieved and enable their further assembly into larger structures. The DX tiles, defined by Fu and Seeman in 1993, each contain two independent crossover points that join two adjacent DNA helices to form a rigid tile with the axes of the helices between the crossovers arranged roughly coplanar. Five types of DX tiles were initially reported: two antiparallel and three parallel molecules that differed in the relative orientation of the helical domains, the arrangement of the constituent strands, and the distance between the crossover points. DAE and DAO molecules (double-crossover antiparallel molecules with an even number or odd number of half turns between crossover points along the same two helices) were later applied to DNA origami designs with great success, largely because these tiles contain two unperturbed DNA strands of opposing polarity that are easily linked to form a scaffold strand. In that case, the antiparallel scaffold is wound back and forth in a raster fill pattern to form a particular shape, through the use of hundreds of staple strands. In contrast, DPE (double-crossover parallel molecules with an even number of half turns between crossover points) molecules were not thoroughly explored for the construction of higher-order structures. Compared to antiparallel DX molecules, parallel DX molecules are generally regarded as less stable presumably because of stronger electrostatic repulsion between the opposing DNA backbones. Later, Sherman and co-workers reported that strand end-pinning and misfolding caused by the structural bias of nominally flexible junctions might affect the proper structural formation of parallel DX molecules. Breaking the continuity of one of the two strands that comprise each junction in a DPE tile at the junction point will produce parallel, double-helical units with single-crossover linkages between the helices. Such modified DPE tiles provide a direct solution to both the possible steric hindrance at the crossover points and the kinetic trap noted by Sherman and co-workers. Herein, we demonstrate that the unperturbed strands in these modified DPE tiles can be linked to form a long scaffold strand that is directed by a collection of staple strands to form DNA origami structures. The scaffold strand in adjacent helices possesses the same 5’–3’ polarity and we therefore refer to these structures as parallel helix (PH) origami. Assembling PH origami required that we develop unique, coiled-scaffold folding paths rather than the typical raster fill patterns adopted by the scaffold in DNA origami structures with antiparallel helices (AH). We also designed and assembled hybrid DNA origami structures that contain both parallel and antiparallel scaffold regions. The DAE, DPE, and modified DPE tiles are shown in Figure 1A–C for comparison. The single-stranded DNA (depicted in gray) remains unperturbed at all junction points and the relative polarities of these two strands determine whether the molecules are classified as antiparallel or parallel. The remaining DNA strands are shown in various colors and correspond to the staple strands that direct/hold the linear strands in a coplanar arrangement. The staple strands in the antiparallel tiles (Figure 1A) reverse direction at each crossover point while those in the parallel tiles (Figure 1B) do not. Note that the backbones of the strands at the crossover points in the parallel tiles are directly opposite one another, which imparts a certain degree of instability to the parallel tiles. Thus, in the modified DPE tiles (Figure 1C), a single-crossover linkage replaces the typical reciprocal [*] Dr. D. Han, S. Jiang, A. Samanta, Prof. Y. Liu, Prof. H. Yan The Biodesign Institute, Arizona State University Tempe, AZ 85287 (USA) E-mail: hao.yan@asu.edu

Self-assembling nucleic acid molecules have shown merit as versatile materials for organizing and constructing nanoscale structures with both 2D and 3D geometries. This chapter focuses on strategies in designing DNA gridiron nanostructures based on four-arm junction. This design strategies aims at controlling DNA self-assembly with a higher degree of spatial precision by depicting arbitrary 3D geometries with their wireframe outlines using DNA helices (for edges) and four-arm junctions (for vertices).

Self-assembling nucleic acid molecules have shown merit as versatile materials for organizing and constructing nanoscale structures with both 2D and 3D geometries. This chapter focuses on strategies in designing DNA gridiron nanostructures based on four-arm junction. This design strategies aims at controlling DNA self-assembly with a higher degree of spatial precision by depicting arbitrary 3D geometries with their wireframe outlines using DNA helices (for edges) and four-arm junctions (for vertices).

DNA molecules have been used to build a variety of nanoscale structures and devices over the past 30 years, and potential applications have begun to emerge. But the development of more advanced structures and applications will require a number of issues to be addressed, the most significant of which are the high cost of DNA and the high error rate of self-assembly. Here we examine the technical challenges in the field of structural DNA nanotechnology and outline some of the promising applications that could be developed if these hurdles can be overcome. In particular, we highlight the potential use of DNA nanostructures in molecular and cellular biophysics, as biomimetic systems, in energy transfer and photonics, and in diagnostics and therapeutics for human health.

Researchers have been using DNA for the rational design and construction of nanoscale objects for nearly 30 years. Recently, 'scaffolded DNA origami' has emerged as one of the most promising assembly techniques in DNA nanotechnology with a broad range of applications. In the past two years alone, DNA origami has been used to assemble water-soluble probe tiles for label-free RNA hybridization, to study single-molecule chemical reactions, to probe distance-dependent multivalent ligand-protein binding effects, and to organize a variety of relevant molecules including proteins, carbon nanotubes, and metal nanoparticles. This review will recount the origin, evolution, and current status of this extremely versatile assembly technique.

Engineering wireframe architectures and scaffolds of increasing complexity is one of the important challenges in nanotechnology. We present a design strategy to create gridiron-like DNA structures. A series of four-arm junctions are used as vertices within a network of double-helical DNA fragments. Deliberate distortion of the junctions from their most relaxed conformations ensures that a scaffold strand can traverse through individual vertices in multiple directions. DNA gridirons were assembled, ranging from two-dimensional arrays with reconfigurability to multilayer and three-dimensional structures and curved objects.

Scaffolded DNA origami is a widely used technology for self-assembling precisely structured nanoscale objects that contain a large number of addressable features. Typical scaffolds are long, single strands of DNA (ssDNA) that are folded into distinct shapes through the action of many, short ssDNA staples that are complementary to several different domains of the scaffold. However, sources of long single-stranded DNA are scarce, limiting the size and complexity of structures that can be assembled. Here we demonstrated that dsDNA (double-stranded DNA) scaffolds can be directly used to fabricate integrated DNA origami structures that incorporate both of the constituent ssDNA molecules. Two basic principles were employed in the design of scaffold folding paths: folding path asymmetry and periodic convergence of the two ssDNA scaffold strands. Asymmetry in the folding path minimizes unwanted complementarity between staples, and incorporating an offset between the folding paths of each ssDNA scaffold strand reduces the number of times that complementary portions of the strands are brought into close proximity with one another, both of which decrease the likelihood of dsDNA scaffold recovery. Meanwhile, the folding paths of the two ssDNA scaffold strands were designed to periodically converge to promote the assembly of a single, unified structure rather than two individual ones. Our results reveal that this basic strategy can be used to reliably assemble integrated DNA nanostructures from dsDNA scaffolds.

Here we report the colloidal synthesis of size-tunable SnS nanocrystals that have an unusual meta-stable cubic zinc-blende phase instead of the more stable layered orthorhombic phase. The single-crystalline zinc-blende SnS nanocrystals with sizes of 8 nm, 60 nm, and 700 nm were achieved by injecting the sulfur-oleylamine precursor into tin-oleylamine solution in the presence of hexamethyldisilazane (HMDS) at different temperatures. The morphology and structure of the SnS nanocrystals were studied by high-resolution electron microscopy techniques. The small SnS nanoparticles (∼8 nm and ∼60 nm) are nearly spherical and have the polyhedral shape. The large (∼700 nm) crystals display a unique crystal morphology that have T(d) symmetry with a truncated tetrahedron configuration, and the four truncated surfaces each outgrow to form a convex triangular pyramid corner. Careful structural analysis revealed that each of the crystal is enclosed by 4 low-index {111} hexangular facets and 12 high-index {220} triangular facets using a lift-out technique with a focused ion beam (FIB) and followed by high resolution electron microscope imaging. The direct band gaps of the different sized SnS nanocrystals range from 1.63 eV to 1.68 eV. These heavy-metal-free and low cost nanocrystals are highly efficient absorptive materials in the whole UV-visible range, suitable for applications in photovoltaic cells.

A conductive nanoporous antimony-doped tin oxide (ATO) powder has been prepared using the sol-gel method that contains three-dimensionally interconnected pores within the metal oxide and highly tunable pore sizes on the nanoscale. It is demonstrated that these porous materials possess the capability of hosting a tetrahedral-shaped DNA nanostructure of defined dimensions with high affinity. The tunability of pore size enables the porous substrate to selectively absorb the DNA nanostructures into the metal oxide cavities or exclude them from entering the surface layer. Both confocal fluorescence microscopy and solution FRET experiments revealed that the DNA nanostructures maintained their integrity upon the size-selective incorporation into the cavities of the porous materials. As DNA nanostructures can serve as a stable three-dimensional nanoscaffold for the coordination of electron transfer mediators, this work opens up new possibilities of incorporating functionalized DNA architectures as guest molecules to nanoporous conductive metal oxides for applications such as photovoltaics, sensors, and solar fuel cells.

We present a strategy to design and construct self-assembling DNA nanostructures that define intricate curved surfaces in three-dimensional (3D) space using the DNA origami folding technique. Double-helical DNA is bent to follow the rounded contours of the target object, and potential strand crossovers are subsequently identified. Concentric rings of DNA are used to generate in-plane curvature, constrained to 2D by rationally designed geometries and crossover networks. Out-of-plane curvature is introduced by adjusting the particular position and pattern of crossovers between adjacent DNA double helices, whose conformation often deviates from the natural, B-form twist density. A series of DNA nanostructures with high curvature--such as 2D arrangements of concentric rings and 3D spherical shells, ellipsoidal shells, and a nanoflask--were assembled.

Topology is the mathematical study of the spatial properties that are preserved through the deformation, twisting and stretching of objects. Topological architectures are common in nature and can be seen, for example, in DNA molecules that condense and relax during cellular events1. Synthetic topological nanostructures, such as catenanes and rotaxanes, have been engineered using supramolecular chemistry, but the fabrication of complex and reconfigurable structures remains challenging2. Here, we show that DNA origami3 can be used to assemble a Mobius strip, a topological ribbon-like structure that has only one side4,5,6. In addition, we show that the DNA Mobius strip can be reconfigured through strand displacement7 to create topological objects such as supercoiled ring and catenane structures. This DNA fold-and-cut strategy, analogous to Japanese kirigami8, may be used to create and reconfigure programmable topological structures that are unprecedented in molecular engineering. A Mobius strip — a ribbon-like structure with only one side — can be assembled from DNA origami and then reconfigured into various topologies by cutting along the length of the strip.