O-nitrobenzyl Caged Molecule Enables Photo-controlled Release of Thiabendazole.

Pesticides are essential in agricultural development. Controlled-release pesticides have attracted great attentions. Base on a principle of spatiotemporal selectivity, we extended the photoremovable protective group (PRPG) into agrochemical agents to achieve controllable release of active ingredients. Herein, we obtained NP-TBZ by covalently linking o-nitrobenzyl (NP) with thiabendazole (TBZ). Compound NP-TBZ can be controlled to release TBZ in dependent to light. The irradiated and unirradiated NP-TBZ showed significant differences on fungicidal activities both in vitro and in vivo. In addition, the irradiated NP-TBZ displayed similar antifungal activities to the directly-used TBZ, indicating a factual applicability in controllable release of TBZ. Furthermore, we explored the action mode and microcosmic variations by SEM analysis, and demonstrated that the irradiated NP-TBZ retained a same action mode with TBZ against mycelia growth.

Pharmacokinetic/Pharmacodynamic Assessment of the Structural Refinement of Clopidogrel Focusing on the Balance between Bioactivation and Deactivation.

The delicate balance between ischemic and bleeding risks is a critical factor in antiplatelet therapy administration. Clopidogrel and prasugrel, belonging to the thienopyridine class of antiplatelet drugs, are known for their variability in individual responsiveness and high incidence of bleeding events, respectively. The present study is centered on the development and assessment of a range of deuterated thienopyridine derivatives, leveraging insights from structure-pharmacokinetic relationships of clopidogrel and prasugrel. Our approaches were grounded in the molecular framework of clopidogrel and incorporated the C2-pharmacophore design from prasugrel. The selection of ester or carbamate substituents at the C2-position facilitated the generation of the 2-oxointermediate through hydrolysis, akin to prasugrel, thereby bypassing the issue of CYP2C19 dependency. The bulky C2-pharmacophore in our approach distinguishes itself from prasugrel's acetyloxy substituent by exhibiting a moderated hydrolysis rate, resulting in a more gradual formation of the active metabolite. Excessive and rapid release of the active metabolite, believed to be linked with an elevated risk of bleeding, is thus mitigated. Our proposed structural modification retains the hydrolysis-sensitive methyl ester of clopidogrel but substitutes it with a deuterated methyl group, shown to effectively reduce metabolic deactivation. Three promising compounds demonstrated a pharmacokinetic profile similar to that of clopidogrel at four times the dose, while also augmenting its antiplatelet activity. SIGNIFICANCE STATEMENT: Inspired by the structure-pharmacokinetic relationship of clopidogrel and prasugrel, a range of clopidogrel derivatives were designed, synthesized, and assessed. Among them, three promising compounds have been identified, striking a delicate balance between efficacy and safety for antiplatelet therapy. Additionally, the ozagrel prodrug conjugate was discovered to exert a synergistic therapeutic effect alongside clopidogrel.

Design, Synthesis, and Synergistic Activities of Eight-Membered Carbon Bridged Neonicotinoid Derivatives.

Insecticide synergists are an effective approach to increase the control efficacy and reduce active ingredient usage. In order to explore neonicotinoid-specific synergists with novel scaffolds and higher potency, a series of eight-membered carbon bridged neonicotinoid derivatives were designed and synthesized in accordance with our previous research. The synergistic effects of the target compounds on neonicotinoids in Aphis craccivora were evaluated, and the structure-activity relationships were summarized. The results indicated that most of the target compounds exhibited significant synergistic effects on imidacloprid in A. craccivora at low concentrations. In particular, compound 1 at a concentration of 1 mg/L reduced the LC50 value of imidacloprid from 0.856 mg/L to 0.170 mg/L. Meanwhile, compound 1 also increased the insecticidal activity of most neonicotinoid insecticides belonging to the Insecticide Resistance Action Committee (IRAC) 4 A subgroup against A. craccivora. The present study might be meaningful for directing the design of neonicotinoid-specific synergists.

CCDN-DETR: A Detection Transformer Based on Constrained Contrast Denoising for Multi-Class Synthetic Aperture Radar Object Detection.

The effectiveness of the SAR object detection technique based on Convolutional Neural Networks (CNNs) has been widely proven, and it is increasingly used in the recognition of ship targets. Recently, efforts have been made to integrate transformer structures into SAR detectors to achieve improved target localization. However, existing methods rarely design the transformer itself as a detector, failing to fully leverage the long-range modeling advantages of self-attention. Furthermore, there has been limited research into multi-class SAR target detection. To address these limitations, this study proposes a SAR detector named CCDN-DETR, which builds upon the framework of the detection transformer (DETR). To adapt to the multiscale characteristics of SAR data, cross-scale encoders were introduced to facilitate comprehensive information modeling and fusion across different scales. Simultaneously, we optimized the query selection scheme for the input decoder layers, employing IOU loss to assist in initializing object queries more effectively. Additionally, we introduced constrained contrastive denoising training at the decoder layers to enhance the model's convergence speed and improve the detection of different categories of SAR targets. In the benchmark evaluation on a joint dataset composed of SSDD, HRSID, and SAR-AIRcraft datasets, CCDN-DETR achieves a mean Average Precision (mAP) of 91.9%. Furthermore, it demonstrates significant competitiveness with 83.7% mAP on the multi-class MSAR dataset compared to CNN-based models.

Extra-High Mechanical and Phononic Anisotropy in Black Phosphorus Blisters.

Strain is an effective strategy to modulate the electrical, optical, and optoelectronic properties of 2D materials. Conventional circular blisters could generate a biaxial stretching of 2D membranes with notable strain gradients along the hoop direction. However, such a deformation mode cannot be utilized to investigate mechanical responses of in-plane anisotropic 2D materials, for example, black phosphorus (BP), due to its crystallographic orientation dependence. Here, a novel rectangular-shaped bulge device is developed to uniaxially stretch the membrane, and further provide a promising platform to detect orientation-dependent mechanical and optical properties of anisotropic 2D materials. Impressively, the derived anisotropic ratio of Young's modulus of BP flakes is much higher than the values obtained via the nanoindentation method. The extra-high strain-dependent phononic anisotropy in Raman modes along different crystalline orientations is also observed. The designed rectangular budge device expands the uniaxial deformation methods available, allowing to explore the mechanical, and strain-dependent physical properties of other anisotropic 2D materials more broadly.

Dual photo-controlled release system for fipronil and dinotefuran.

Development of controlled release system promises a huge impact on the pesticide delivery, which has raised attentions in improving efficacy of pesticides. Herein, the emerging photoremovable protecting group (PRPG), used in spatiotemporal delivery of drug by light, was introduced into agriculture. We obtained three TNB-insecticides and two of them exhibited excellent photophysicochemical properties. Our dual photo-controlled release system displayed more than sixfold insecticidal activity differences upon irradiation with UV light or sunlight. The dual release of DIN-TNB-DIN showed synergistic effect on mosquito larvae and armyworm larvae. Distribution of the fluorescence in body of dead/alive wigglers clearly illustrated the action mode, and visually demonstrated the precise and spatiotemporal delivery of insecticides in the living mosquito larvae. The new developed dual photo-controlled release system might widen the diversity in pesticide delivery, promoting the development in improving pesticide efficacy.

Vertical strain engineering of Van der Waals heterostructures.

Van der Waals materials and their interfaces play critical roles in defining electrical contacts for nanoelectronics and developing vehicles for mechanoelectrical energy conversion. In this work, we propose a vertical strain engineering approach by enforcing pressure across the heterostructures. First-principles calculations show that the in-plane band structures of 2D materials such as graphene, h-BN, and MoS2as well as the electronic coupling at their contacts can be significantly modified. For the graphene/h-BN contact, a band gap in graphene is opened, while at the graphene/MoS2interface, the band gap of MoS2and the Schottky barrier height at contact diminish. Changes and transitions in the nature of contacts are attributed to localized orbital coupling and analyzed through the redistribution of charge densities, the crystal orbital Hamilton population, and electron localization, which yield consistent measures. These findings offer key insights into the understanding of interfacial interaction between 2D materials as well as the efficiency of electronic transport and energy conversion processes.

Rolling circle transcription: A new system to produce RNA microspheres for improving RNAi efficiency in an agriculturally important lepidopteran pest (Mythimna separate).

We applied a new RNA interference (RNAi) system using rolling circle transcription (RCT) technology to generate RNA microspheres (RMS) for targeting two key chitin synthetic pathway genes [chitin synthase A (CHSA), chitin synthase B (CHSB)] in the larvae of the oriental armyworm (Mythimna separate), a RNAi-unsusceptible agriculturally important lepidopteran pest. Feeding the third-instar larvae with the RMS-CHSA- or RMS-CHSB-treated corn leaf discs suppressed the expression of CHSA by 81.7% or CHSB by 88.1%, respectively, at 72 h. The silencing of CHSA consequently affected the larval development, including the reduced body weight (54.0%) and length (41.3%), as evaluated on the 7th day, and caused significant larval mortalities (51.1%) as evaluated on the 14th day. Similar results were obtained with the larvae fed RMS-CHSB. We also compared RNAi efficiencies among different strategies: 1) two multi-target RMS [i.e., RMS-(CHSA + CHSB), RMS-CHSA + RMS-CHSB], and 2) multi-target RMS and single-target RMS (i.e., either RMS-CHSA or RMS-CHSB) and found no significant differences in RNAi efficiency. By using Cy3-labeled RMS, we confirmed that RMS can be rapidly internalized into Sf9 cells (<6 h). The rapid cellular uptake of RMS accompanied with significant RNAi efficiency through larval feeding suggests that the RCT-based RNAi system can be readily applied to study the gene functions and further developed as bio-pesticides for insect pest management. Additionally, our new RNAi system takes the advantage of the microRNA (miRNA)-mediated RNAi pathway using miRNA duplexes generated in vivo from the RMS by the target insect. The system can be used for RNAi in a wide range of insect species, including lepidopteran insects which often exhibit extremely low RNAi efficiency using other RNAi approaches.

Belief Propagation Optimization for Lossy Compression Based on Gaussian Source.

In the Internet of Things, sensor nodes collect environmental information and utilize lossy compression for saving storage space. To achieve this objective, high-efficiency compression of the continuous source should be studied. Different from existing schemes, lossy source coding is implemented based on the duality principle in this work. Referring to the duality principle between the lossy source coding and the channel decoding, the belief propagation (BP) algorithm is introduced to realize lossy compression based on a Gaussian source. In the BP algorithm, the log-likelihood ratios (LLRs) are iterated, and their iteration paths follow the connecting relation between the check nodes and the variable nodes in the protograph low-density parity-check (P-LDPC) code. During LLR iterations, the trapping set is the main factor that influences compression performance. We propose the optimized BP algorithms to weaken the impact of trapping sets. The simulation results indicate that the optimized BP algorithms obtain better distortion-rate performance.

Analysis and Optimization of a General Linking Matrix for JSCC Scheme Based on Double LDPC Codes.

A key component of the joint source-channel coding (JSCC) scheme based on double low-density parity-check (D-LDPC) codes is the introduction of a linking matrix between the source LDPC code and channel LDPC code, by which the decoding information including the source redundancy and channel state information can be transferred iteratively. However, the linking matrix is a fixed one-to-one mapping, i.e., an identity matrix in a conventional D-LDPC code system, which may not take full advantage of the decoding information. Therefore, this paper introduces a general linking matrix, i.e., a non-identity linking matrix, connecting the check nodes (CNs) of the source LDPC code and the variable nodes (VNs) of the channel LDPC code. Further, the encoding and decoding algorithms of the proposed D-LDPC coding system are generalized. A joint extrinsic information transfer (JEXIT) algorithm is derived for calculating the decoding threshold of the proposed system with a general linking matrix. In addition, several general linking matrices are optimized with the aid of the JEXIT algorithm. Finally, the simulation results demonstrate the superiority of the proposed D-LDPC coding system with general linking matrices.

High-strength scalable graphene sheets by freezing stretch-induced alignment.

ABSTRACCT: Efforts to obtain high-strength graphene sheets by near-room-temperature assembly have been frustrated by the misalignment of graphene layers, which degrades mechanical properties. While in-plane stretching can decrease this misalignment, it reappears when releasing the stretch. Here we use covalent and π-π inter-platelet bridging to permanently freeze stretch-induced alignment of graphene sheets, and thereby increase isotropic in-plane sheet strength to 1.55 GPa, in combination with a high Young's modulus, electrical conductivity and weight-normalized shielding efficiency. Moreover, the stretch-bridged graphene sheets are scalable and can be easily bonded together using a commercial resin without appreciably decreasing the performance, which establishes the potential for practical applications.

Anisotropic Fracture of Graphene Revealed by Surface Steps on Graphite.

The anisotropic fracture toughness G(θ) is an intrinsic feature of graphene and is fundamental for fabrication, functioning, and robustness of graphene-based devices. However, existing results show significant discrepancies on the anisotropic factor, i.e., the ratio between zigzag (ZZ) and armchair (AC) directions, G_{ZZ}/G_{AC}, both qualitatively and quantitatively. Here, we investigate the anisotropic fracture of graphene by atomic steps on cleaved graphite surfaces. Depending on the relation between the peeling direction and local lattice orientation, two categories of steps with different structures and behaviors are observed. In one category are straight steps well aligned with local ZZ directions, while in the other are steps consisting of nanoscale ZZ and AC segments. Combined with an analysis on fracture mechanics, the microscale morphology of steps and statistics of their directions provides a measurement on the anisotropic factor of G_{ZZ}/G_{AC}=0.971, suggesting that the ZZ direction has a slightly lower fracture toughness. The results provide an experimental benchmark for the widely scattered existing results, and offer constraints on future models of graphene fracture.

Study on the Interaction between Deuterium Clopidogrel and Omeprazole.

INTRODUCTION: Dual antiplatelet therapy with aspirin in combination with a P2Y12 receptor antagonist is a cornerstone for treating patients with acute coronary syndrome and in percutaneous coronary intervention. However, as this combination of antiplatelet therapy increases the risk of bleeding, proton pump inhibitors (PPIs) are currently recommended to prevent gastrointestinal ulcers and bleeding. The cytochrome P450 (CYP450) isoenzyme system metabolizes both clopidogrel (CLP) and PPIs. Unfortunately, omeprazole (OM) reduce the antiplatelet activity of CLP and increases the probability of recurrence of cardiovascular events by competitively inhibiting the CYP450 isoenzyme CYP2C19. METHODS: To address these abovementioned problems, we designed and synthesized deuterium CLP (D-CL) using selective deuterium technology. Our previous research results showed that D-CL had better pharmacokinetic and pharmacodynamic properties. Thus, the HPLC-MS/MS method, cocktail method, Born method, electro-stimulated thrombus generation, and thrombus elastography were used to detect the production of thiol active metabolites (AM), CYP450 enzyme activities, platelet aggregation, time and length of thrombus formation, and the maximum clot strength after combination therapy. We investigated the pharmacokinetics and pharmacodynamics properties of D-CL combined with OM. RESULTS: As compared to CLP, D-CL was less affected when combined with OM, which was reflected in lower inhibitory effects of CYP450 enzyme activities, a greater area under the curve of AM, and better antiplatelet and antithrombotic effects. CONCLUSION: D-CL may reduce drug-drug interactions and address the clinical disadvantages of CLP.

4-Oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-d]pyrimidine Derivatives: Design, Synthesis, Insecticidal Assay and Binding Mode Studies.

A series of 4-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-d]pyrimidine derivatives were designed and synthesized based on the fipronil low energy conformation by scaffold hopping strategy. Physicochemical properties calculation, insecticidal assay and binding mode studies were also performed. It was found that the target compounds displayed lower insecticidal activities than fipronil. The differences in binding modes between these compounds and fipronil may be the major reason for reduced insecticidal activities.

Pattern Development and Control of Strained Solitons in Graphene Bilayers.

Engineering strain and interlayer registry in 2D crystals have been demonstrated as effective controls of their properties. Separation of domains with different interlayer registries in graphene bilayer has been reported, but the pattern control of strained solitons has not yet been achieved. We show here that, by pulling a graphene bilayer apart, soliton structures with a regularly modulated interlayer registry arise from the competition between elastic deformation in monolayers and local slip at the van der Waals interfaces. The commensurate-incommensurate transition with strain localization is identified as the interlayer overlap exceeds a critical size, where the continuum description of load transfer through the tension-shear chain breaks down. Birth, development and annihilation processes of the strained solitons can be controlled by the loading conditions. The effects of lattice symmetry and mechanical constraints are also discussed, completing the picture for microstructural evolution processes in the homo- or heterostructures of 2D crystals.

Biomimetic Mechanically Enhanced Carbon Nanotube Fibers by Silk Fibroin Infiltration.

Natural materials, such as silk, nacre, and bone, possess superior mechanical properties which are derived from their unique hierarchical structures. Individual carbon nanotubes (CNTs) are considered as one of the strongest materials. However, macroscopic CNT fibers usually have breaking strength far below that of individual CNTs. In this work, by mimicking the structure of natural silk fibers, strong and stiff CNT fibers are prepared by infiltrating silk fibroin (SF) into CNT fibers. There are abundant hydrogen bonds in SF, contributing to the enhanced interactions between neighboring CNTs. Glycerol is selected to promote the formation of ß-sheet conformation in SF, leading to further enhanced strength and modulus. Remarkably, the SF infiltrated CNT fibers show breaking strength of 1023 MPa, toughness of 10.3 MJ m-3 , and Young's modulus of 81.3 GPa, which are 250%, 132%, and 442% of the pristine CNT fibers. The structure of the SF and the interactions between CNTs and SF are studied via Fourier transformed infrared spectroscopy and molecular dynamics simulation. Mimicking the hierarchical structures of natural silk fibers and enhance the interfacial load transfer by infiltrating SF are effective for reinforcing CNT fibers, which may be useful in the design and preparation of other structural materials.

Electronic excitation in graphene under single-particle irradiation.

Single-particle irradiation is a typical condition in space applications, which could be detrimental for electronic devices through processes such as single-event upset or latch-up. For functional devices made of few-atom-thick monolayers that are entirely exposed to the environment, the irradiation effects could be manifested through localized or delocalized electronic excitation, in addition to lattice defect creation. In this work, we explore the single-H irradiation effects on bare or coated graphene monolayers. Real-time time-dependent density functional theory-based first-principles calculation results elucidate the evolution of charge densities in the composite system, showing notable charge excitation but negligible charge deposition. A hexagonal boron nitride coating layer does not protect graphene from these processes. Principal component analysis demonstrates the dominance of localized excitation accompanied by nuclear motion, bond distortion and vibration, as well as a minor contribution from delocalized plasmonic excitation. The significance of coupled electron-ion dynamics in modulating the irradiation processes is identified from comparative studies on the spatial and temporal patterns of excitation for unconstrained and constrained lattices. The stopping power or energy deposition is also calculated, quantifying the dissipative nature of charge density excitation. This study offers fundamental understandings of the single-particle irradiation effects on optoelectronic devices constructed from low-dimensional materials, and inspires unconventional techniques to excite the electrons and ions in a controllable way.

Spatiotemporal Mobility Based Trajectory Privacy-Preserving Algorithm in Location-Based Services.

Recent years have seen the wide application of Location-Based Services (LBSs) in our daily life. Although users can enjoy many conveniences from the LBSs, they may lose their trajectory privacy when their location data are collected. Therefore, it is urgent to protect the user's trajectory privacy while providing high quality services. Trajectory k-anonymity is one of the most important technologies to protect the user's trajectory privacy. However, the user's attributes are rarely considered when constructing the k-anonymity set. It results in that the user's trajectories are especially vulnerable. To solve the problem, in this paper, a Spatiotemporal Mobility (SM) measurement is defined for calculating the relationship between the user's attributes and the anonymity set. Furthermore, a trajectory graph is designed to model the relationship between trajectories. Based on the user's attributes and the trajectory graph, the SM based trajectory privacy-preserving algorithm (MTPPA) is proposed. The optimal k-anonymity set is obtained by the simulated annealing algorithm. The experimental results show that the privacy disclosure probability of the anonymity set obtained by MTPPA is about 40% lower than those obtained by the existing algorithms while the same quality of services can be provided.

Nanoconfinement-Enforced Ion Correlation and Nanofluidic Ion Machinery.

Machines operating at the atomic level are of fundamental interests for information manipulation and communication. However, preparation of thermodynamically stable states and regulation of transitions between them at a low energy cost are challenging. We report that, by enforcing nanoconfinement and surface gating, one can control the configurations and dynamics of ions for computational tasks. The layered structures of water confined in nanochannels render the spatial and temporal correlation between ions, offering a number of distinct states with paired configurations. Free energy barriers for transitions between them are on the order of kBT, allowing modulation through external fields or surface charges at a low energy cost. Ionic switches, rectifiers, and logical gates are constructed following the physical rules elucidated at the molecular level, opening an avenue toward artificial nanofluidic functionalities such as efficient ionic machinery by configuring the ionic pairs and controlled mass/charge transport by tuning the strength of correlation.

How Universal Is the Wetting Aging in 2D Materials.

Previous studies indicate that 2D materials such as graphene, WS2, and MoS2 deposited on oxidized silicon substrate are susceptible to aging due to the adsorption of airborne contamination. As a result, their surfaces become more hydrophobic. However, it is not clear how ubiquitous such a hydrophobization is, and the interplay between the specific adsorbed species and resultant wetting aging remains elusive. Here, we report a pronounced and general hydrophilic-to-hydrophobic wetting aging on 2D InSe films, which is independent of the substrates to synthesize these films (silicon, glass, nickel, copper, aluminum oxide), though the extent of wetting aging is sensitive to the layer of films. Our findings are ascribed to the occurrence and enrichment of airborne contamination that contains alkyl chains. Our results also suggest that the wetting aging effect might be universal to a wide range of 2D materials.