A two-step electrochemical biosensor based on Tetrazyme for the detection of fibrin.

In this study, an electrochemical biosensor was constructed for the detection of fibrin, specifically by a simple two-step approach, with a novel artificial enzyme (Tetrazyme) based on the DNA tetrahedral framework as signal probe. The multichannel screen-printed electrode with the activated surface cannot only remove some biological impurities, but also serve as a carrier to immobilize a large number of antigen proteins. The DNA tetrahedral nanostructure was employed to ensure the high sensitivity of the probe for biological analysis. The hemin was chimeric into the G-quadruplex to constitute the complex with peroxidase catalytic activity (hemin/G4-DNAzyme), subsequently, Tetrazyme was formed through combining of this complex and DNA tetrahedral nucleic acid framework. The artificial enzyme signal probe formed by the covalent combination of the homing peptide (Cys-Arg-Glu-Lys-Ala, CREKA), which is the aptamer of fibrin and the new artificial enzyme is fixed on the surface of the multichannel carbon electrode by CREKA-specific recognition, so as to realize the sensitive detection of fibrin. The feasibility of sensing platform was validated by cyclic voltammetry (CV) and amperometric i-t curve (IT) methods. Effects of Tetrazyme concentration, CREKA concentrations and hybridization time on the sensor were explored. Under the best optimal conditions of 0.6 µmol/L Tetrazyme, 80 µmol/L CREKA, and 2.5 h reaction time, the immunosensor had two linear detection ranges, 10-40 nmol/L, with linear regression equation Y = 0.01487X - 0.011 (R2 = 0.992), and 50-100 nmol/L, with linear regression equation Y = 0.00137X + 0.6405 (R2 = 0.998), the detection limit was 9.4 nmol/L, S/N ≥ 3. The biosensor could provide a new method with great potential for the detection of fibrin with good selectivity, stability, and reproducibility.

DNA tetrahedron-based dual-signal fluorescence detection of apoE4 gene sites on a microplate reader.

As a neurodegenerative disorder, Alzheimer's disease (AD) is characterized by cognitive dysfunction and behavioral impairment. Among the various genetic risk factors for AD, apoE4 gene plays a pivotal role in the onset and progression of AD, and detection of apoE4 gene holds significance for prevention and early diagnosis of AD. Herein, dual-signal fluorescence detection of fragments associated with apoE ε4 allele near codon 112 (Tc1) and codon 158 (Tc2) was achieved using DNA tetrahedron nanostructure (DTN). The Förster resonance energy transfer (FRET) process in the DTN was initiated in which the nucleic acid intercalating dye thiazole orange (TO) served as the donor and the cyanine dyes of cyanine3 (Cy3) and cyanine5 (Cy5) at the two vertices of DTN served as the acceptors. In the presence of Tc1 and Tc2, the FRET process between TO and the cyanine dyes was hindered by the enzymatic cleavage reaction, which ensures the dual-signal fluorescence assay of apoE4 gene sites. The limit of detection for Tc1 and Tc2 was estimated to be 0.82 nM and 0.77 nM, respectively, and the whole assay was accomplished within 1 h on a microplate reader. The proposed method thus possesses the advantages of easy operation, short detection time, and high-throughput capability.

Improved Tumor Infiltration and Immunomodulation for Tumor Therapy: A Pathway Based on Tetrahedral Framework Nucleic Acids Coupled Bacterial Nanocells.

Growing evidence indicates that the tumor microenvironment (TME) can be combined with other therapeutic modalities, including cytotoxic chemotherapy and targeted therapies, to produce unanticipated results in oncology treatment. Here, we proposed a novel bacterial nanomaterial capable of targeting peritumoral biofilm and modulating TME. It was based on tetrahedral framework nucleic acids (T) that were chemically attached to aptamer AS1411 and 5-fluorouracil (AT5). Additionally, the oral pathogenic bacterium Streptococcus mutans (S.m) was employed as a biocarrier for synergetic biofilm targeting and immunomodulation. In this article, the effect of AT5-coupled S.m-derived nanocells (S.m-AT5) was investigated in vitro and in vivo. Due to bacteria aggregation in the tumor-specific biofilm, these nanocells released greater medication concentrations. Furthermore, they exerted an immunomodulatory effect by stimulating the maturation of dendritic cells (DCs) and regulation of T cells. This chemo-immunostimulation combination has a powerful antitumor impact. It may also be an advanced approach for boosting the survival rate of cancer patients.

Multipartite Entanglement: A Journey through Geometry.

Genuine multipartite entanglement is crucial for quantum information and related technologies, but quantifying it has been a long-standing challenge. Most proposed measures do not meet the "genuine" requirement, making them unsuitable for many applications. In this work, we propose a journey toward addressing this issue by introducing an unexpected relation between multipartite entanglement and hypervolume of geometric simplices, leading to a tetrahedron measure of quadripartite entanglement. By comparing the entanglement ranking of two highly entangled four-qubit states, we show that the tetrahedron measure relies on the degree of permutation invariance among parties within the quantum system. We demonstrate potential future applications of our measure in the context of quantum information scrambling within many-body systems.

Stabilizing Sulfur Sites in Tetraoxygen Tetrahedral Coordination Structure for Efficient Electrochemical Water Oxidation.

Ion regulation strategy is regarded as a promising pathway for designing transition metal oxide-based electrocatalysts for oxygen evolution reaction (OER) with improved activity and stability. Precise anion conditioning can accurately change the anionic environment so that the acid radical ions (SO4 2- , PO3 2- , SeO4 2- , etc.), regardless of their state (inside the catalyst, on the catalyst surface, or in the electrolyte), can optimize the electronic structure of the cationic active site and further increase the catalytic activity. Herein, we report a new approach to encapsulate S atoms at the tetrahedral sites of the NaCl-type oxide NiO to form a tetraoxo-tetrahedral coordination structure (S-O4 ) inside the NiO (S-NiO -I). Density functional theory (DFT) calculations and operando vibrational spectroscopy proves that this kind of unique structure could achieve the S-O4 and Ni-S stable structure in S-NiO-I. Combining mass spectroscopy characterization, it could be confirmed that the S-O4 structure is the key factor for triggering the lattice oxygen exchange to participate in the OER process. This work demonstrates that the formation of tetraoxygen tetrahedral structure is a generalized key for boosting the OER performances of transition metal oxides.

Three-in-One Strategy Constructing the First High-Performance Nonlinear Optical Sulfide Crystallizing with the P43 Space Group.

The balance between large nonlinear optical (NLO) effect and wide bandgap is the key scientific issue for the exploration of infrared NLO materials. Targeting this issue, two new pentanary chalcogenides KGaGe1.37 Sn0.63 S6 (1) and KGaGe1.37 Sn0.63 Se6 (2) are obtained by the three-in-one strategy, viz. three types of fourfold-coordinated metal elements co-occupying the same site. They crystallize in the tetragonal P43 (1) and monoclinic Cc (2) space group. Their structures can be evolved from benchmark AgGaS2 (AGS) by suitable substitution. Remarkably, 1 is the first NLO sulfide crystallizing with the P43 space group, representing a new structure-type NLO material. The structural relationship between 1 and 2 and the evolution from 1, 2 to AGS are also analyzed. Both 1 and 2 show balanced NLO properties. Specifically, 1 exhibits phase-matchable SHG response of 0.6 × AGS, a wide bandgap of 3.50 eV, and a high laser damage threshold of 6.24 × AGS. Theoretical calculation results suggest that the Ga/Ge/Sn element ratios of the co-occupied sites of 1 and 2 are the most appropriate for stabilizing the structures. The strategy adopted here will provide some inspiration for exploring new high-performance NLO materials.

Studying Wild Plant Pathosystems to Understand Crop Plant Pathosystems: Status, Gaps, Challenges, and Perspectives.

Phytopathology is a highly complex scientific discipline. Initially, its focus was on the study of plant-pathogen interactions in agricultural and forestry production systems. Host-pathogen interactions in natural plant communities were generally overlooked until the 1970s when plant pathologists and evolutionary biologists started to take an interest in these interactions, and their dynamics in natural plant populations, communities, and ecosystems. This article introduces the general principles of plant pathosystems, provides a basic critical overview of current knowledge of host-pathogen interactions in natural plant pathosystems, and shows how this knowledge is important for future developments in plant pathology especially as it applies in cropping systems, ecology, and evolutionary biology. Plant pathosystems can be further divided according to the structure and origin of control, as autonomous (wild plant pathosystems, WPPs) or deterministic (crop plant pathosystems, CPPs). WPPs are characterized by the disease triangle and closed-loop (feedback) controls, and CPPs are characterized by the disease tetrahedron and open-loop (non-feedback) controls. Basic general, ecological, genetic, and population structural and functional differences between WPPs and CPPs are described. It is evident that we lack a focus on long-term observations and research of diseases and their dynamics in natural plant populations, metapopulations, communities, ecosystems, and biomes, as well as their direct or indirect relationships to CPPs. Differences and connections between WPPs and CPPs, and why, and how, these are important for agriculture varies. WPP and CPP may be linked by strong biological interactions, especially where the pathogen is in common. This is demonstrated through a case study of lettuce (Lactuca spp., L. serriola and L. sativa) and lettuce downy mildew (Bremia lactucae). In other cases where there is no such direct biological linkage, the study of WPPs can provide a deeper understanding of how ecology and genetics interacts to drive disease through time. These studies provide insights into ways in which farming practices may be changed to limit disease development. Research on interactions between pathosystems, the "cross-talk" of WPPs and CPPs, is still very limited and, as shown in interactions between wild and cultivated Lactuca spp.-B. lactucae associations, can be highly complex. The implications and applications of this knowledge in plant breeding, crop management, and disease control measures are considered. This review concludes with a discussion of theoretical, general and specific aspects, challenges and limits of future WPP research, and application of their results in agriculture.

Determining the Cytosolic Stability of Small DNA Nanostructures In Cellula.

DNA nanostructures have proven potential in biomedicine. However, their intracellular interactions─especially cytosolic stability─remain mostly unknown and attempts to discern this are confounded by the complexities of endocytic uptake and entrapment. Here, we bypass the endocytic uptake and evaluate the DNA structural stability directly in live cells. Commonly used DNA structures─crosshairs and a tetrahedron─were labeled with a multistep Förster resonance energy transfer dye cascade and microinjected into the cytosol of transformed and primary cells. Energy transfer loss, as monitored by fluorescence microscopy, reported the structure's direct time-resolved breakdown in cellula. The results showed rapid degradation of the DNA crosshair within 20 min, while the tetrahedron remained consistently intact for at least 1 h postinjection. Nuclease assays in conjunction with a current understanding of the tetrahedron's torsional rigidity confirmed its higher stability. Such studies can inform design parameters for future DNA nanostructures where programmable degradation rates may be required.

The Effects of Mono- and Bivalent Linear Alkyl Interlayer Spacers on the Photobehavior of Mn(II)-Based Perovskites.

Mn(II)-based perovskite materials are being intensively explored for lighting applications; understanding the role of ligands regarding their photobehavior is fundamental for their development. Herein, we report on two Mn (II) bromide perovskites using monovalent (perovskite 1, P1) and bivalent (perovskite 2, P2) alkyl interlayer spacers. The perovskites were characterized with powder X-ray diffraction (PXRD), electron spin paramagnetic resonance (EPR), steady-state, and time-resolved emission spectroscopy. The EPR experiments suggest octahedral coordination in P1 and tetrahedral coordination for P2, while the PXRD results demonstrate the presence of a hydrated phase in P2 when exposed to ambient conditions. P1 exhibits an orange-red emission, while P2 shows a green photoluminescence, as a result of the different types of coordination of Mn(II) ions. Furthermore, the P2 photoluminescence quantum yield (26%) is significantly higher than that of P1 (3.6 %), which we explain in terms of different electron-phonon couplings and Mn-Mn interactions. The encapsulation of both perovskites into a PMMA film largely increases their stability against moisture, being more than 1000 h for P2. Upon increasing the temperature, the emission intensity of both perovskites decreases without a significant shift in the emission spectrum, which is explained in terms of an increase in the electron-phonon interactions. The photoluminescence decays fit two components in the microsecond regime-the shortest lifetime for hydrated phases and the longest one for non-hydrated phases. Our findings provide insights into the effects of linear mono- and bivalent organic interlayer spacer cations on the photophysics of these kinds of Mn (II)-based perovskites. The results will help in better designs of Mn(II)-perovskites, to increase their lighting performance.

[Intelligent co-design of material, process, and equipment for manufacturing high-quality traditional Chinese medicine preparations].

In the context of Pharma 4.0, the design tools that support the pharmaceutical Quality by Design(QbD) are iterating fast toward intelligent or smart design. The conventional development methods for traditional Chinese medicine(TCM) preparations have the limitations such as over dependence on experience, low dimensions for the designed experiment parameters, poor compatibility between the process and equipment, and high trial-and-error cost during process scale-up. Therefore, this paper innovatively proposed the intelligent co-design involving material, process, and equipment for manufacturing high-quality TCM preparations, and introduced the design philosophy, targets, tools, and applications with TCM oral solid dosage(OSD) as an example. In terms of design philosophy, the pharmaceutical design tetrahedron composed of critical material attributes, critical process parameters, critical equipment attributes, and critical quality attributes was developed. The design targets were put forward based on the product performance classification system. The design tools involve a design platform that contains several modules, such a as the iTCM material database, the processing route classification system, the system modeling and simulation, and reliability-based optimization. The roles of different modules in obtaining essential and universal design knowledge of the key common manufacturing units were introduced. At last, the applications of the co-design methodology involving material, process, and equipment in the high shear wet granulation process development and the improvement of the dissolving or dispersion capability of TCM formula granules are illustrated. The research on advanced pharmaceutical design theory and methodology will help enhance the efficiency and reliability of drug development, improve the product quality, and promote the innovation of high-end TCM products across the industry.

The Marriage of Sierpinski Triangles and Platonic Polyhedra.

Fractal structures with self-similarity are of fundamental importance in the fields of aesthetic, chemistry and mathematics. Here, by taking advantage of constructs the rational geometry-directed precursor design, we report the construction of two fascinating Platonic solids, the Sierpinski tetrahedron ST-T and the Sierpinski octahedron ST-O, in which each possesses a fractal Sierpinski triangle on their independent faces. These two discrete complexes are formed in near-quantitative yield from the multi-component self-assembly of truncated Sierpinski triangular kernel L1 with tribenzotriquinacene-based hexatopic and anthracene-based tetratopic terpyridine ligands (L3 and L4 ) in the presence of metal ions, respectively. The enhanced stabilities of the 3D discrete structures were investigated by gradient tandem mass spectrometry (gMS2 ). This work provides new constructs for the imitation of complex virus assemblies and for the molecular encapsulation of giant guest molecules.

Time-dependent density functional theory study of the optical properties of tetrahedral aluminum nanoparticles.

The plasmonic properties of tetrahedral aluminum nanoparticles have been investigated using time-dependent functional theory (TDDFT) calculations. The excitation energies are calculated for tetrahedral aluminum nanoparticles (Aln , n = 10-120) with different charge states. The BP86/DZ model is used to perform geometric optimization calculations for these clusters. The SAOP/DZ and LB94/DZ levels of theory have been used for the excitation energy calculations of these tetrahedral aluminum clusters. The absorption peaks are red-shifted upon increasing the size of the aluminum nanoparticles.

Differentiable Formation of Chiroptical Lanthanide Heterometallic Lnn Ln'4-n (L6 ) (n=0-4) Tetrahedra with C2 -Symmetrical Bis(tridentate) Ligands.

Construction of lanthanide heterometallic complex is important for engineering multifunction molecular containers. However, it remains a challenge because of the similar ionic radii of lanthanides. Herein we attempt to prepare chiral lanthanide heterometallic tetrahedra. Upon crystallization with a mixture of [Eu2 L3 ] and [Ln2 L3 ] (Ln=Gd, Tb and Dy) helicates, a mixture of heterometallic Eun Ln'4-n (L6 ) (n=0-4) tetrahedra was prepared. Selective formation of heterometallic tetrahedron was observed as MS deconvolution results deviated from statistical results. The formation of heterometallic tetrahedron was found to be sensitive to ionic radii as well as the ratio of the two helicates used in the crystallization.

Localized DNA tetrahedrons assisted catalytic hairpin assembly for the rapid and sensitive profiling of small extracellular vesicle-associated microRNAs.

The profiling of small extracellular vesicle-associated microRNAs (sEV-miRNAs) plays a vital role in cancer diagnosis and monitoring. However, detecting sEV-miRNAs with low expression in clinical samples remains challenging. Herein, we propose a novel electrochemical biosensor using localized DNA tetrahedron-assisted catalytic hairpin assembly (LDT-CHA) for sEV-miRNA determination. The LDT-CHA contained localized DNA tetrahedrons with CHA substrates, leveraging an efficient localized reaction to enable sensitive and rapid sEV-miRNA measurement. Based on the LDT-CHA, the proposed platform can quantitatively detect sEV-miRNA down to 25 aM in 30 min with outstanding specificity. For accurate diagnosis of gastric cancer patients, a combination of LDT-CHA and a panel of four sEV-miRNAs (sEV-miR-1246, sEV-miR-21, sEV-miR-183-5P, and sEV-miR-142-5P) was employed in a gastric cancer cohort. Compared with diagnosis with single sEV-miRNA, the proposed platform demonstrated a higher accuracy of 88.3% for early gastric tumor diagnoses with higher efficiency (AUC: 0.883) and great potential for treatment monitoring. Thus, this study provides a promising method for the bioanalysis and determination of the clinical applications of LDT-CHA.

A pH-engineering regenerative DNA tetrahedron ECL biosensor for the assay of SARS-CoV-2 RdRp gene based on CRISPR/Cas12a trans-activity.

In this work, we constructed an exonuclease III cleavage reaction-based isothermal amplification of nucleic acids with CRISPR/Cas12a-mediated pH-induced regenerative Electrochemiluminescence (ECL) biosensor for ultrasensitive and specific detection of SARS-CoV-2 nucleic acids for SARS-CoV-2 diagnosis. The triple-stranded nucleic acid in this biosensor has an extreme dependence on pH, which makes our constructed biosensor reproducible. This is essential for effective large-scale screening of SARS-CoV-2 in areas where resources are currently relatively scarce. Using this pH-induced regenerative biosensor, we detected the SARS-CoV-2 RdRp gene with a detection limit of 43.70 aM. In addition, the detection system has good stability and reproducibility, and we expect that this method may provide a potential platform for the diagnosis of COVID-19.

A novel measure to analyze protein structures: Aspect ratio in protein alpha shapes.

Proteins' three-dimensional (3D) structures are analyzed traditionally using geometric descriptors such as torsional angles and inter-atomic distances. In this study a measure that is borrowed from computational geometry, aspect ratio of each tetrahedron in alpha shapes of proteins, is utilized. This geometric descriptor differentiates alpha and beta structural classes of proteins when combined with principal components analysis. The method converts the structures of individual proteins, 3D coordinates of the atoms, to points on a plane. It has a high degree of accuracy in differentiating R and T structures of hemoglobin. Therefore, it is anticipated that the geometric measure can be used successfully in a method that is extended to solve classification problems in machine learning.

Emerging Yttrium Phosphides with Tetrahedron Phosphorus and Superconductivity under High Pressures.

Metal phosphides have triggered growing interest for their exotic structures and striking properties. Hence, within advanced structure search and first-principle calculations, several unprecedented Y-P compounds (e. g., Y3 P, Y2 P, Y3 P2 , Y2 P3 , YP2 , and YP3 ) were identified under compression. Interestingly, as phosphorus content increases, P atoms exhibit diverse behaviors corresponding to standalone anion, dumbbell, zigzag chain, planar sheet, crossing chain-like network, buckled layer, three-dimensional framework, and wrinkled layer. Particularly, Fd-3m YP2 can be viewed as assemblage of diamond-like Y structure and rare vertex-sharing tetrahedral P4  units. Impressively, electron-phonon coupling (EPC) calculations elucidate that Pm-3m Y3 P possesses the highest superconducting critical temperature Tc of 10.2 K among binary transition metal phosphides. Remarkably, the EPC of Pm-3m Y3 P mainly arises from the contribution of low-frequency soft phonon modes, whereas mid-frequency phonon modes of Fd-3m YP2 dominate. These results strengthen knowledge of metal phosphides and pave a way for seeking superconductive transition metal phosphides.

Case report: Fabrication of a dental implant guide based on tetrahedron positioning technology.

BACKGROUND: Conventional static computer-assisted implant surgery (s-CAIS) requires special equipment, such as 3D printers or computer numerical control (CNC) lathes. We present a low-cost workflow for manufacturing dental implant guides based on tetrahedron positioning technology (TPT). The aim of this case report was to use a surgical guide technique for dental implant placement using tetrahedron positioning technology. CASE PRESENTATION: A 28-year-old man consulted for the treatment of a missing right first mandibular molar by implant placement. The cone-beam computed tomography (CBCT) data were imported into medical image processing software for analysis, and the implant design was simulated. The implant design on CBCT was transferred to the mandibular model using TPT, and the implant surgical guide was made to guide the dental implant operation. CBCT was performed postoperatively and compared with the preoperative design to check the accuracy. The central deviation of the implant head was 0.31 mm, the central deviation of the implant apex was 0.93 mm, and the implant angular deviation was 2.45°. CONCLUSION: The use of tetrahedral positioning technology based on CBCT data is a new method for making implant guides. It is a promising technique offering a highly predictable outcome and lower risk of iatrogenic damage. However, these results should be interpreted with care since they are based on limited evidence from a case report. Larger population studies with longer follow-up periods and standardized experimental studies are required.

"Tell me about": a logbook of teachers' changes from face-to-face to distance mathematics education.

In 2020, the emergency due to the COVID-19 pandemic brought a drastic and sudden change in teaching practices, from the physical space of the classrooms to the virtual space of an e-environment. In this paper, through a qualitative analysis of 44 collected essays composed by Italian mathematics teachers from primary school to undergraduate level during the spring of 2020, we investigate how the Italian teachers perceived the changes due to the unexpected transition from a face-to-face setting to distance education. The analysis is carried out through a double theoretical lens, one concerning the whole didactic system where the knowledge at stake is mathematics and the other regarding affective aspects. The integration of the two theoretical perspectives allows us to identify key elements and their relations in the teachers' narratives and to analyze how teachers have experienced and perceived the dramatic, drastic, and sudden change. The analysis shows the process going from the disruption of the educational setting to the teachers' discovery of key aspects of the didactic system including the teacher's roles, a reflection on mathematics and its teaching, and the attempt to reconstruct the didactic system in a new way.

Tetrahedral DNA nanostructures as drug delivery and bioimaging platforms in cancer therapy.

Structural DNA nanotechnology enables DNA to be used as nanomaterials for novel nanostructure construction with unprecedented functionalities. Artificial DNA nanostructures can be designed and generated with precisely controlled features, resulting in its utility in bionanotechnological and biomedical applications. A tetrahedral DNA nanostructure (TDN), the most popular DNA nanostructure, with high stability and simple synthesis procedure, is a promising candidate as nanocarriers in drug delivery and bioimaging platforms, particularly in precision medicine as well as diagnosis for cancer therapy. Recent evidence collectively indicated that TDN successfully enhanced cancer therapeutic efficiency both in vitro and in vivo. Here, we summarize the development of TDN and highlight various aspects of TDN applications in cancer therapy based on previous reports, including anticancer drug loading, photodynamic therapy, therapeutic oligonucleotides, bioimaging platforms, and other molecules and discuss a perspective in opportunities and challenges for future TDN-based nanomedicine.