Chalcone-Based Synthesis of Tetrahydropyridazines via Cloke-Wilson-Type Rearrangement-Involved Tandem Reaction between Cyclopropyl Ketones and Hydrazines.

A facile and efficient approach for the synthesis of multisubstituted tetrahydropyridazines starting from cyclopropyl ketones and hydrazines has been developed. The transformation is chalcone-based and takes place via a Cloke-Wilson-type rearrangement-involved tandem reaction catalyzed by TfOH in HFIP.

Homogenization characteristics and regional effects in the diversity pattern of woody plants in 101 cities in China.

Influenced by the interplay of global climate change and urbanization, urban plants have become increasingly homogenized in China. However, regional effects of biotic homogenization cannot be clearly explained due to the lack of continuous large-scale data. Thus, we explored the characteristics and regional effects of biotic homogenization, which not only contributes to the improvement of urban biodiversity, but also has important value for human well-being. Here, we analyzed the woody plants of 101 cities in 8 major urban agglomerations in China. The diversity patterns and influencing factors were explored using generalized additive, geographically weighted regression, and structural equation models. The main results were as follows: (1) The issue of woody plant homogenization is primarily manifested in urban greening species in China. (2) The characteristics of woody plant homogenization exhibit notable regional effects at a large scale. (3) Latitude, urban area, altitude and climatic factors all impact the woody plant homogenization. Thus, we found that the homogenization characteristics of urban greening species exhibit regional variations, influenced by both natural and anthropogenic factors. Finally, we suggested that urban biodiversity management should be considered specific regional environmental, both to meet the needs of residents.

Synthesis of Phenolic Coumestans via a Sequential Dehydrogenation/Oxa-Michael Addition Reaction of 2',4'-Dihydroxyl-3-arylcoumarins.

A facile and practical approach for the synthesis of natural coumestans and derivatives starting from 2',4'-dihydroxyl-3-arylcoumarins has been developed. The process involved a seqential intramolecular dehydrogenation/oxa-Micheal reaction efficiently promoted by 1,8-diazabicyclo[5.4.0]undec-7-ene at 40 °C under metal- and ligand-free conditions with good functional group compatibility.

Annulation of ß-naphthols and 4-hydroxycoumarins with vinylsulfonium salts: synthesis of dihydrofuran derivatives.

A new synthetic approach to dihydrofuran derivatives via the annulation reaction of ß-naphthols and 4-hydroxycoumarins with vinylsulfonium salts has been developed. A variety of dihydrofuran derivatives were prepared in moderate to good yields under mild conditions. The products could be readily transformed to the corresponding furans via the dehydrogenation with DDQ.

[Analysis of the internal atmosphere of tableware disinfection cabinet].

OBJECTIVE: To analyze the internal atmosphere of tableware disinfection cabinet, determine the composition and sources of odor gas. METHODS: Analyze the internal atmosphere of tableware disinfection cabinet by solid phase microextraction (SPME) with gas chromatography-mass spectrometry (GC-MS), and study the relationship between organic gas and auxiliary materials by simulating sterilization conditions. RESULTS: The organic gas had been detected in tableware disinfection cabinet both before and after use of it. The paint film and the sealing strip produced 56 and 76 kinds of organic gaseous substances after one cycle of sterilizer work respectively. Both UV irradiation and heating processes made the sealing strip produce 56 kinds of organic gaseous substances. CONCLUSION: UV irradiation and heating will induce auxiliary mainly came from the auxiliary material.

Invasion stage and competition intensity co-drive reproductive strategies of native and invasive saltmarsh plants: Evidence from field data.

Biological invasion poses a significant threat to biodiversity conservation and also results in substantial economic loss including the excessive cost of management to control it. Still, its impact on plant sexual reproduction strategies remains underexplored in natural settings. We conducted a field experiment on native Phragmites australis and invasive Spartina alterniflora in Bohai Bay and assessed plant size (aboveground biomass and height) and sexual reproduction (ear biomass, reproductive allocation, etc.) in conjunction with water and soil properties. The results showed that during the early stage of invasion, the two species declined in size and sexual reproduction, with S. alterniflora showing a lesser decline than P. australis. However, in the late stage of invasion, S. alterniflora maintained its plant size by reducing its investment in sexual reproduction. Moreover, significant reproductive allometries were demonstrated by S. alterniflora under different competition intensities. P. australis displayed heightened sensitivity to water properties and soil non-resource conditions, while S. alterniflora adapted its inherent traits and environmental tolerance. S. alterniflora allocated more resources to thriving as an individual, while P. australis prioritized reproduction by increasing seed production. Overall, this study revealed the reproductive strategies that invasive and native species employ in response to competition and environmental factors, thereby offering crucial insights for conservation and management efforts.

Carbamoylation at C-8 position of natural 3-arylcoumarin scaffold for the discovery of novel PARP-1 inhibitors with potent anticancer activity.

Structural modification based on natural privileged scaffolds has proven to be an attractive approach to generate potential antitumor candidates with high potency and specific targeting. As a continuation of our efforts to identify potent PARP-1 inhibitors, natural 3-arylcoumarin scaffold was served as the starting point for the construction of novel structural unit for PARP-1 inhibition. Herein, a series of novel 8-carbamyl-3-arylcoumarin derivatives were designed and synthesized. The antiproliferative activities of target compounds against four BRCA-mutated cancer cells (SUM149PT, HCC1937, MDA-MB-436 and Capan-1) were evaluated. Among them, compound 9b exhibited excellent antiproliferative effects against SUM149PT, HCC1937 and Capan-1 cells with IC50 values of 0.62, 1.91 and 4.26 µM, respectively. Moreover, 9b could significantly inhibit the intracellular PARP-1/2 activity in SUM149PT cells with IC50 values of 2.53 nM and 6.45 nM, respectively. Further mechanism studies revealed that 9b could aggravate DNA double-strand breaks, increase ROS production, decrease mitochondrial membrane potential, arrest cell cycle at G2/M phase and ultimately induce apoptosis in SUM149PT cells. In addition, molecular docking study demonstrated that the binding mode of 9b with PARP-1 was similar to that of niraparib, forming multiple hydrogen bond interactions with the active site of PARP-1. Taken together, these findings suggest that 8-carbamyl-3-arylcoumarin scaffold could serve as an effective structural unit for PARP-1 inhibition and offer a valuable paradigm for the structural modification of natural products.

Origins of brain tissue elasticity under multiple loading modes by analyzing the microstructure-based models.

Constitutive behaviors and material properties of brain tissue play an essential role in accurately modeling its mechanical responses. However, the measured mechanical behaviors of brain tissue exhibit a large variability, and the reported elastic modulus can differ by orders of magnitude. Here we develop the micromechanical models based on the actual microstructure of the longitudinally anisotropic plane of brain tissue to investigate the microstructural origins of the large variability. Specifically, axonal fiber bundles with the specified configurations are distributed in an equivalent matrix. All micromechanical models are subjected to multiple loading modes, such as tensile, compressive, and shear loading, under periodic boundary conditions. The predicted results agree well with the experimental results. Furthermore, we investigate how brain tissue elasticity varies with its microstructural features. It is revealed that the large variability in brain tissue elasticity stems from the volume fraction of axonal fiber, the aspect ratio of axonal fiber, and the distribution of axonal fiber orientation. The volume fraction has the greatest impact on the mechanical behaviors of brain tissue, followed by the distribution of axonal fiber orientation, then the aspect ratio. This study provides critical insights for understanding the microstructural origins of the large variability in brain tissue elasticity.

Mechanical mechanism and indicator of diffuse axonal injury under blast-type acceleration.

Diffuse axonal injury (DAI) caused by acceleration is one of the most prominent forms of blast-induced Traumatic Brain Injury. However, the mechanical mechanism and indicator of axonal deformation-induced injury under blast-type acceleration with high peak and short duration are unclear. This study constructed a multilayer head model that can reflect the response characteristics of translational and rotational acceleration (the peak time of which is within 0.5 ms). Based on von Mises stress, axonal strain and axonal strain rate indicators, the physical process of axonal injury is studied, and the vulnerable area under blast-type acceleration load is given. In the short term (within 1.75 ms), dominated by sagittal rotational acceleration peaks, the constraint of falx and tentorium rapidly imposes the inertial load on the brain tissue, resulting in a high-rate deformation of axons (axonal strain rate of which exceed 100 s-1). For a long term (after 1.75 ms), fixed-point rotation of the brain following the head causes excessive distortion of brain tissue (von Mises stress of which exceeds 15 kPa), resulting in a large axonal stretch strain where the main axonal orientation coincides with the principal strain direction. It is found that the axonal strain rate can better indicate the pathological axonal injury area and coincides with external inertial loading in the risk areas, which suggests that DAI under blast-type acceleration overload is mainly caused by the rapid axonal deformation instead of by the excessive axonal strain. The research in this paper helps understand and diagnose blast-induced DAI.

A Bayesian method with nonlinear noise model to calibrate constitutive parameters of soft tissue.

The measured mechanical responses of soft tissue exhibit large variability and errors, especially for the softest brain tissue, while calibrating its constitutive parameters in a deterministic way remains a common practice. Here we implement a Bayesian method considering the nonlinear noise model to calibrate constitutive parameters of brain tissue. A probability model is first developed based on the measured experimental data, likelihood function, and prior function, from which the posterior distributions of model parameters are formulated. The likelihood function considers the nonlinear behaviors of the constitutive response and noise distribution of the experimentally measured data. Meanwhile, the prior predictive distribution is computed to check the probability model preliminarily. Secondly, the Markov Chain Monte Carlo (MCMC) method is used to compute the posterior distributions of model parameters, enabling assessment of parameter uncertainty, correlation, and model calibration error. Finally, the posterior predictive distributions of the overall response, constitutive response, and noise response are computed to validate the probabilistic model, all of which are consistent with the corresponding data. Furthermore, the effect of the prior distribution, experimental data, and noise model on posterior distribution is studied. Our study provides a general approach to calibrating constitutive parameters of soft tissue despite errors and large variability in experimental data.

Revealing the Effect of Skull Deformation on Intracranial Pressure Variation During the Direct Interaction Between Blast Wave and Surrogate Head.

Intracranial pressure (ICP) during the interaction between blast wave and the head is a crucial evaluation criterion for blast-induced traumatic brain injury (bTBI). ICP variation is mainly induced by the blast wave transmission and skull deformation. However, how the skull deformation influences the ICP remains unclear, which is meaningful for mitigating bTBI. In this study, both experimental and numerical models are developed to elucidate the effect of skull deformation on ICP variation. Firstly, we performed the shock tube experiment of the high-fidelity surrogate head to measure the ICP, the blast overpressure, and the skull surface strain of specific positions. The results show that the ICP profiles of all measured points show oscillations with positive and negative change, and the variation is consistent with the skull surface strain. Further numerical analysis reveals that when the blast wave reaches the measured point, the peak overpressure transmits directly through the skull to the brain, forming the local positive ICP peak, and the impulse induces the local inward deformation of the skull. As the peak overpressure passes through, the blast impulse impacts the nearby skull supported by the soft and incompressible brain tissue and extrudes the skull outward in the initial position. The inward and outward skull deformation leads to the oscillation of ICP. These numerical analyses agree with experimental results, which explain the appearance of negative and positive ICP peaks and the synchronization of negative ICP with surface strain. The study has implications for medical injury diagnosis and protective equipment design.

Dual-Signal Amplification Strategy for Sensitive MicroRNA Detection Based on Rolling Circle Amplification and Enzymatic Repairing Amplification.

MicroRNAs (miRNAs) play crucial regulatory roles as post-transcriptional regulators for gene expression and serve as promising biomarkers for diagnosis and prognosis of diseases. Herein, a dual-signal amplification method has been developed for sensitive and selective detection of miRNA based on rolling circle amplification (RCA) and enzymatic repairing amplification (ERA) with low nonspecific background. This strategy designs a padlock probe that can be cyclized in the presence of target miRNA to initiate the RCA reaction, after which the TaqMan probes that are complementary to the RCA products can be cyclically cleaved to produce obvious fluorescence signals with the help of endonuclease IV (Endo IV). Attributed to the dual-signal amplification procedure and the high fidelity of Endo IV, the RCA-ERA method allows quantitative detection of miR-21 in a dynamic range from 2 pM to 5 nM with a low background signal. Moreover, it has the ability to discriminate single-base difference between miRNAs and shows good performance for miRNA detection in complex biological samples. The results demonstrate that the RCA-ERA assay holds a great promise for miRNA-based diagnostics.

Copper-catalyzed intramolecular cross dehydrogenative coupling approach to coumestans from 2'-hydroxyl-3-arylcoumarins.

A copper-catalyzed intramolecular cross dehydrogenative C-O coupling reaction of 2'-hydroxyl-3-arylcoumarins was developed. This protocol provided a facile and efficient strategy for the construction of natural coumestans and derivatives in moderate to high yields. This transformation exhibited good functional group compatibility and was amenable to substrates with free phenolic hydroxyl groups.

Development of a validated HPLC method for the quantitative determination of trelagliptin succinate and its related substances in pharmaceutical dosage forms.

Trelagliptin succinate is a dipeptidyl peptidase IV (DPP-4) inhibitor which is used as a new long-acting drug for once-weekly treatment of type 2 diabetes mellitus (DM). In the present study, a rapid, sensitive and accurate high-performance liquid chromatography (HPLC) method was developed and validated for separation and determination of trelagliptin succinate and its eight potential process-related impurities. The chromatographic separation was achieved on a Waters Xselect CSH™ C18 (250mm×4.6mm, 5.0µm) column. The mobile phases comprised of 0.05% trifluoroacetic acid in water as well as acetonitrile containing 0.05% trifluoroacetic acid. The compounds of interest were monitored at 224nm and 275nm. The stability-indicating capability of this method was evaluated by performing stress test studies. Trelagliptin succinate was found to degrade significantly in acid, base, oxidative and thermal stress conditions and only stable in photolytic degradation condition. The degradation products were well resolved from the main peak and its impurities. In addition, the major degradation impurities formed under acid, base, oxidative and thermal stress conditions were characterized by ultra-high-performance liquid chromatography coupled with linear ion trap-Orbitrap tandem mass spectrometry (UHPLC-LTQ-Orbitrap). The method was validated to fulfill International Conference on Harmonisation (ICH) requirements and this validation included specificity, linearity, limit of detection (LOD), limit of quantification (LOQ), accuracy, precision and robustness. The developed method in this study could be applied for routine quality control analysis of trelagliptin succinate tablets, since there is no official monograph.

From tunneling to hopping: a comprehensive investigation of charge transport mechanism in molecular junctions based on oligo(p-phenylene ethynylene)s.

The charge transport mechanism of oligo(p-phenylene ethynylene)s with lengths ranging from 0.98 to 5.11 nm was investigated using modified scanning tunneling microscopy break junction and conducting probe atomic force microscopy methods. The methods were based on observing the length dependence of molecular resistance at single molecule level and the current-voltage characteristics in a wide length distribution. An intrinsic transition from tunneling to hopping charge transport mechanism was observed near 2.75 nm. A new transitional zone was observed in the long length molecular wires compared to short ones. This was not a simple transition between direct tunneling and field emission, which may provide new insights into transport mechanism investigations. Theoretical calculations provided an essential explanation for these phenomena in terms of molecular electronic structures.