On the numerical corroboration of an obstacle problem for linearly elastic flexural shells.

In this article, we study the numerical corroboration of a variational model governed by a fourth-order elliptic operator that describes the deformation of a linearly elastic flexural shell subjected not to cross a prescribed flat obstacle. The problem under consideration is modelled by means of a set of variational inequalities posed over a non-empty, closed and convex subset of a suitable Sobolev space and is known to admit a unique solution. Qualitative and quantitative numerical experiments corroborating the validity of the model and its asymptotic similarity with Koiter's model are also presented.This article is part of the theme issue 'Non-smooth variational problems with applications in mechanics'.

Dysregulation of the Suprachiasmatic Nucleus Disturbs the Circadian Rhythm and Aggravates Epileptic Seizures by Inducing Hippocampal GABAergic Dysfunction in C57BL/6 Mice.

The interplay between circadian rhythms and epilepsy has gained increasing attention. The suprachiasmatic nucleus (SCN), which acts as the master circadian pacemaker, regulates physiological and behavioral rhythms through its complex neural networks. However, the exact role of the SCN and its Bmal1 gene in the development of epilepsy remains unclear. In this study, we utilized a lithium-pilocarpine model to induce epilepsy in mice and simulated circadian disturbances by creating lesions in the SCN and specifically knocking out the Bmal1 gene in the SCN neurons. We observed that the pilocarpine-induced epileptic mice experienced increased daytime seizure frequency, irregular oscillations in core body temperature, and circadian gene alterations in both the SCN and the hippocampus. Additionally, there was enhanced activation of GABAergic projections from the SCN to the hippocampus. Notably, SCN lesions intensified seizure activity, concomitant with hippocampal neuronal damage and GABAergic signaling impairment. Further analyses using the Gene Expression Omnibus database and gene set enrichment analysis indicated reduced Bmal1 expression in patients with medial temporal lobe epilepsy, potentially affecting GABA receptor pathways. Targeted deletion of Bmal1 in SCN neurons exacerbated seizures and pathology in epilepsy, as well as diminished hippocampal GABAergic efficacy. These results underscore the crucial role of the SCN in modulating circadian rhythms and GABAergic function in the hippocampus, aggravating the severity of seizures. This study provides significant insights into how circadian rhythm disturbances can influence neuronal dysfunction and epilepsy, highlighting the therapeutic potential of targeting SCN and the Bmal1 gene within it in epilepsy management.

Poling-assisted hydrofluoric acid wet etching of thin-film lithium niobate.

Thin-film lithium niobate (TFLN) has been extensively investigated for a wide range of applications due to continuous advancements in its fabrication methods. The recent emergence of high-fidelity ferroelectric domain poling of TFLN provides an opportunity for achieving a precise pattern control of ferroelectric domains and a subsequent pattern transfer to the TFLN layer using hydrofluoric acid (HF). In this work, we present, to the best of our knowledge, the first demonstration of z-cut TFLN microdisks using a poling-assisted HF wet etching approach. By applying intense electric fields, we are able to induce a domain inversion in the TFLN with a designed microdisk pattern. A HF solution is subsequently utilized to transfer the inverted domain pattern to the TFLN layer with the selective etching of -z LN, ultimately revealing the microdisks.

Rapid Construction of Vinyl Indomorphans by Rhenium Catalysis.

Here, an efficient route for accessing the vinylindomorphan skeleton is achieved by rhenium(I) catalysis. This transformation involves the condensation of indoles and alkyne-linked cyclohexanones, followed by intramolecular annulation to build the [3.3.1] bicyclic structure. This protocol complements the synthesis of the structurally complex heterocycles bearing a vinyl indole moiety. In addition, the selected products exhibited moderate cytotoxicity toward human A549 cells.

Mechanism of E2F1 in the proliferation, migration, and invasion of endometrial carcinoma cells via the regulation of BMI1 transcription.

BACKGROUND: Endometrial carcinoma (EC) is the most prevalent gynecological cancer. Transcription factor (TF) regulates a large number of downstream target genes and is a key determinant of all physiological activities, including cell proliferation, differentiation, apoptosis, and cell cycle. The transcription factor E2F1 shows prominent roles in EC. BMI1 is a member of Polycomb suppressor Complex 1 (PRC1) and has been shown to be associated with EC invasiveness. It is currently unclear whether E2F1 can participate in the proliferation, migration, and invasion processes of EC cells by regulating BMI1 transcription. OBJECTIVE: We investigated whether E2F1 could participate in the proliferation, migration, and invasion processes of EC cells by regulating BMI1 transcription, in order to further clarify the pathogenesis and etiology of EC, and provide reference for identifying potential therapeutic targets and developing effective prevention and treatment strategies for this disease. METHODS: Human endometrial epithelial cells (hEECs) and human EC cell lines were selected. E2F1 expression was assessed by Western blot. E2F1 was silenced in AN3CA or overexpressed in HEC-1 by transfections, or E2F1 was silenced and BMI1 was overexpressed in AN3CA by cotransfection. Cell proliferation, migration, and invasion were detected by MTT, wound healing, and Transwell assays. The binding sites between E2F1 and BMI1 promoters were predicted through JASPAR website, and the targeted binding was verified by dual-luciferase report and ChIP assays. RESULTS: E2F1 was up-regulated in human EC cell lines, with its expression highest in AN3CA, and lowest in HEC-1. AN3CA invasion, migration, and proliferation were repressed by E2F1 knockdown, while those of HEC-1 cells were promoted by E2F1 overexpression. E2F1 overexpression increased the activity of wild type BMI1 reporter vector promoter, while this promotion was weakened after mutation of the predicted binding site in the BMI1 promoter. In the precipitated E2F1, BMI1 promoter site level was higher than that of IgG immunoprecipitant. BMI1 silencing suppressed AN3CA cell growth. BMI1 overexpression partially abrogated E2F1 silencing-inhibited EC cell growth. CONCLUSION: E2F1 promoted EC cell proliferation, invasion, and migration by promoting the transcription of BMI1.

Hydrophobic Silica Microcavities with Sustainable Nonlinear Photonic Performance.

Ultrahigh quality factor (Q) microcavities have been emerging as appealing compact photonic platforms for various applications. The Q factor plays a critical role in determining the nonlinear optical performance of a microcavity. However, a silica microcavity suffers from severe degradation of its Q value over time during storage or use in air due to the accumulating surface absorption loss, which would deteriorate their nonlinear photonic performance. Here, we report a new type of ultrahigh Q silica microcavity that effectively prevents Q degradation over time. The Q values of the devices remain unchanged over time under storage in air. Optical frequency combs are generated with sustainable ultralow threshold performance over the course of time from the devices in open air. This approach would greatly facilitate ultrahigh Q silica-based photonic devices for next generation photonic applications.

Europium chelate-anionic exchange functionalized covalent organic frameworks for the sensing of aristolochic acid a in humans and sulfamethoxazole/trimethoprim in surface water.

The application of covalent organic frameworks (COFs) in fluorescence detection is of great interest. Herein, we have synthesized the ionic covalent organic framework TGH+·PD: Eu(TTA)4 with the characteristic emission of lanthanides by a straightforward ion-exchange method. This is the first time that aristolochic acid A (AA), a key biomarker for absorption and metabolism in the body for early diagnosis of diseases, has been detected by using COF as a fluorescent probe, which exhibits a good linear correlation with the AA concentration over a range from 5.0 to 1000 µM with a detection limit of 0.0808 µM. In addition, the selective response to sulfamethoxazole (SMZ)/trimethoprim (TMP) is achieved by varying the excitation wavelength with detection lines of 30.2 nM and 2.898 µM, respectively. It is worth mentioning that BNPP has been developed for the accurate determination of SMZ in uncertain samples. In a word, the prepared TGH+·PD: Eu(TTA)4-based sensor can be used for the quantitative detection of AA and SMZ/TMP, separately, effectively extending the application of COFs in the field of fluorescence sensing.

Human umbilical cord mesenchymal stem cell-derived extracellular vesicles improve ovarian function in rats with primary ovarian insufficiency by carrying miR-145-5p.

OBJECTIVE: Stem cell/exosome therapy is a novel strategy for primary ovarian insufficiency (POI). This paper is to examine the role of human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hUCMSC-EVs) in POI. METHODS: hUCMSC-EVs were extracted and identified. POI rats were induced by cyclophosphamide for 15 days and treated with EV or GW4869 every 5 days and euthanized 28 days later. Vaginal smears were observed for 21 days. Serum hormone levels (FSH/E2/AMH) were measured by ELISA. Ovarian morphology, follicle numbers, and granulosa cell (GC) apoptosis were observed by HE and TUNEL staining. GCs extracted from Swiss albino rats were cyclophosphamide-induced to establish the POI cell model, followed by oxidative injury and apoptosis evaluation with the help of DCF-DA fluorescence, ELISA, and flow cytometry. The relation between miR-145-5p and XBP1 was predicted on StarBase and validated by dual-luciferase assay. miR-145-5p and XBP1 levels were measured by RT-qPCR and Western blot. RESULTS: EV treatment reduced irregular estrus cycle incidence since day 7, increased E2 and AMH levels and all-stage follicle numbers, reduced FSH level, GC apoptosis, and atretic follicle numbers in POI rats. EV treatment diminished GC oxidative injury and apoptosis in vitro. miR-145-5p knockdown in hUCMSC-EVs partly abolished hUCMSC-EV-mediated effects on GCs and ovarian function in vivo and on GC oxidative injury and apoptosis in vitro. Silencing XBP1 partially negated miR-145-5p knockdown-exerted effects on GCs in vitro. CONCLUSION: miR-145-5p carried by hUCMSC-EVs attenuates GC oxidative injury and apoptosis and thus extenuates ovarian injury and improves ovarian function in POI rats.

In-situ growth of low-dimensional perovskite-based insular nanocrystals for highly efficient light emitting diodes.

Regulation of perovskite growth plays a critical role in the development of high-performance optoelectronic devices. However, judicious control of the grain growth for perovskite light emitting diodes is elusive due to its multiple requirements in terms of morphology, composition, and defect. Herein, we demonstrate a supramolecular dynamic coordination strategy to regulate perovskite crystallization. The combined use of crown ether and sodium trifluoroacetate can coordinate with A site and B site cations in ABX3 perovskite, respectively. The formation of supramolecular structure retard perovskite nucleation, while the transformation of supramolecular intermediate structure enables the release of components for slow perovskite growth. This judicious control enables a segmented growth, inducing the growth of insular nanocrystal consist of low-dimensional structure. Light emitting diode based on this perovskite film eventually brings a peak external quantum efficiency up to 23.9%, ranking among the highest efficiency achieved. The homogeneous nano-island structure also enables high-efficiency large area (1 cm2) device up to 21.6%, and a record high value of 13.6% for highly semi-transparent ones.

Hydrogel platform capable of molecularly resolved pulling on cells for mechanotransduction.

The active forces exerted from the extracellular matrix (ECM) to mechanoreceptors have crucial impact on many cell functions and disease development. However, our understanding of the underlying mechanisms is held back due to the lack of ECM mimicking platform able to apply molecularly resolved forces to cells. Herein, we present novel hydrogel platform capable of generate pN range forces to specific cellular receptors, at molecular scale. This capability was achieved through near-infrared (NIR) light regulated macromolecular actuators functionalized within the platform. This platform enables us to reveal cell responses to molecularly resolved forces under controlled magnitude (150-400 â€‹pN) and frequency (up to 100 â€‹Hz) on matrix with varied stiffness. We find the stiffness of the matrix has a large influence on the applied force transduction to cells. This versatile platform holds the potential for establishing correlation between receptor signaling pathways and cellular responses closer to physiological conditions.

Research on the function of the Cend1 regulatory mechanism on p75NTR signaling in spinal cord injury.

How to use NSC repair mechanisms, minimize the loss of neurons, and recover the damaged spinal cord functions are hotspots and difficulties in spinal cord injury research. Studies have shown that Cend1 signaling is involved in regulating the NSC differentiation, that p75NTR signaling is involved in the regulation of mature neuronal apoptosis and that NSC differentiation decreases mature neuron apoptosis. Our research group found an interaction between Cend1 and p75NTR, and there was a correlation with spinal cord injury. Therefore, we speculate that Cend1 regulates p75NTR signals and promotes the differentiation of NSCs, and inhibits neuronal apoptosis. Therefore, this study first analyzed the expression of p75NTR and Cend1 in spinal cord injury and its relationship with NSCs and neurons and then analyzed the regulatory mechanism and the mechanism of survival on neuronal apoptosis and differentiation of NSCs. Finally, we analyzed the effect of p75NTR and the regulation of Cend1 damage on functional recovery of the spinal cord with overall intervention. The completion of the subject will minimize the loss of neurons, innovative use of NSC repair mechanisms, and open up a new perspective for the treatment of spinal cord injury.

A palladium-catalyzed ring-expansion reaction of cyclobutanols with 2-haloanilines leading to benzazepines and quinolines.

A general synthesis of 2-aryl benzazepines has been developed through palladium-catalyzed ring-expansion reactions of cyclobutanols with 2-haloanilines; the further oxidative rearrangement reaction of benzazepines provided an efficient synthesis of 2-acyl quinolines. These transformations feature the efficient construction of six- and seven-membered N-containing heterocycles from easily obtained materials with excellent functional group tolerance.

Copper-Catalyzed Selective Defluorinative Sulfuration of Trifluoropropanamides Leading to α-Fluorothioacrylamides.

A practical and efficient method for the synthesis of α-fluorothioacrylamide was developed from selective defluorinative sulfuration of trifluoropropanamides with disulfides. The N-chelation-assisted copper-catalyzed defluorination and sulfurization reactions feature excellent functional group tolerance and incorporation of both sulfur atoms of disulfides into acrylamides.

Bioactive Properties of Peptides and Polysaccharides Derived from Peanut Worms: A Review.

Peanut worms (Sipunculids) are unsegmented marine worms that usually inhabit shallow waters. Peanut worms are good source of bioactive compounds including peptides and polysaccharides. Many recent studies have investigated the bioactive properties of peptides and polysaccharides derived from peanut worms in order to enhance their applications in food and pharmaceutical industries. The peptides and polysaccharides isolated from peanut worms have been reported to possess anti-hypertensive, anti-oxidant, immunomodulatory, anti-inflammatory, anti-cancer, anti-hypoxia and wound healing activities through the modulation of various molecular mechanisms. Most researchers used in vitro, cell culture and animal models for the determination of bioactivities of peanut worm derived compounds. However, studies in humans have not been performed considerably. Therefore, it is important to conduct more human studies for better utilization of marine bioactive compounds (peptides and polysaccharides) derived from peanut worms. This review mainly focuses on the bioactive properties of peptides and polysaccharides of peanut worms and their molecular mechanisms.

Numerical methods for static shallow shells lying over an obstacle.

In this paper, a finite element analysis to approximate the solution of an obstacle problem for a static shallow shell confined in a half space is presented. To begin with, we establish, by relying on the properties of enriching operators, an estimate for the approximate bilinear form associated with the problem under consideration. Then, we conduct an error analysis and we prove the convergence of the proposed numerical scheme.

Microcavity Nonlinear Optics with an Organically Functionalized Surface.

We report enhanced optical nonlinear effects at the surface of an ultrahigh-Q silica microcavity functionalized by a thin layer of organic molecules. The maximal conversion efficiency of third harmonic generation reaches ∼1680%/W^{2} and an absolute efficiency of 0.0144% at pump power of ∼2.90 mW, which is approximately 4 orders of magnitude higher than that in a reported silica microcavity. Further analysis clarifies the elusive dependence of the third harmonic signal on the pump power in previous literature. Molecule-functionalized microcavities may find promising applications in high-efficiency broadband optical frequency conversion and offer potential in sensitive surface analysis.

Gold nanorod enhanced conjugated polymer/photosensitizer composite nanoparticles for simultaneous two-photon excitation fluorescence imaging and photodynamic therapy.

Two-photon photodynamic therapy (2P-PDT) is a novel minimal invasive cancer treatment method with advantages of deep penetration and intrinsic three-dimensionally localized activation to precisely target cancerous tissues. However, the therapeutic efficacy of 2P-PDT is limited by small two-photon absorption cross sections of conventional organic photosensitizers. In addition, traditional photosensitizers generally exhibit weak emission and lack imaging modality. In this work, conjugated polymers and gold nanorods (Au NRs) were integrated to fabricate nano-sized photosensitizers to improve the performance of molecular photosensitizers for 2P-PDT. A molecular photosensitizer, tetraphenylporphyrin, was encapsulated into the conjugated polymer PFV to form conjugated polymer nanoparticles (CPNs), which were then covalently linked to silica coated Au NRs. In these integrated nanoparticles, the two-photon optical properties of tetraphenylporphyrin were first enhanced by fluorescence resonance energy transfer from PFV, then further enhanced by Au NRs through plasmon resonance. A silica shell was utilized as the spacer between Au NRs and CPNs to optimize the enhancement effects. Through the combined enhancement effects of energy transfer and plasmon resonance, two-photon excitation fluorescence and two-photon induced singlet oxygen generation of tetraphenylporphyrin were enhanced by up to 980- and 792-fold, respectively, at a silica spacer thickness of 9 nm. The application of these nanoparticles as photosensitizers for simultaneous two-photon imaging and 2P-PDT treatment have been demonstrated on HeLa cancer cells with high brightness and significantly enhanced cancer cell killing efficiency. These nanoparticles can act as promising nano-photosensitizers for 2P-PDT with simultaneous imaging modality.

Some Effects of Different Constitutive Laws on FSI Simulation for the Mitral Valve.

In this paper, three different constitutive laws for mitral leaflets and two laws for chordae tendineae are selected to study their effects on mitral valve dynamics with fluid-structure interaction. We first fit these three mitral leaflet constitutive laws and two chordae tendineae laws with experimental data. The fluid-structure interaction is implemented in an immersed boundary framework with finite element extension for solid, that is the hybrid immersed boundary/finite element(IB/FE) method. We specifically compare the fluid-structure results of different constitutive laws since fluid-structure interaction is the physiological loading environment. This allows us to look at the peak jet velocity, the closure regurgitation volume, and the orifice area. Our numerical results show that different constitutive laws can affect mitral valve dynamics, such as the transvalvular flow rate, closure regurgitation and the orifice area, while the differences in fiber strain and stress are insignificant because all leaflet constitutive laws are fitted to the same set of experimental data. In addition, when an exponential constitutive law of chordae tendineae is used, a lower closure regurgitation flow is observed compared to that of a linear material model. In conclusion, combining numerical dynamic simulations and static experimental tests, we are able to identify suitable constitutive laws for dynamic behaviour of mitral leaflets and chordae under physiological conditions.

Properties of Love Waves in Functional Graded Saturated Material.

In the present study, the propagation of Love waves is investigated in a layered structure with two different homogeneity saturated materials based on Biot's theory. The upper layer is a transversely isotropic functional graded saturated layer, and the substrate is a saturated semi-space. The inhomogeneity of the functional graded layer is taken into account. Furthermore, the gradient coefficient is employed as the representation of the relation with the layer thickness and the material parameters, and the power series method is applied to solve the variable coefficients governing the equations. In this regard, the influence of the gradient coefficients of saturated material on the dispersion relations, and the attenuation of Love waves in this structure are explored, and the results of the present study can provide theoretical guidance for the non-destructive evaluation of functional graded saturated material.

A geometric model for the human pulmonary valve in its fully open case.

The human pulmonary valve, one of the key cardiac structures, plays an important role in circulatory system. However, there are few mathematical models to accurately simulate it. In this paper, we establish a geometric model of the normal human pulmonary valve from a mathematical perspective in the fully opening case. Based on the statistical data of the human pulmonary valves, we assume that the motions of the three cusps are symmetrical in the cardiac cycle. Thus, we first propose that each cusp is a part of the cylindrical shell according to its structure and physiological feature. The parameters for the pulmonary valve cusps in three-dimensional space are obtained by the fitting functions. We verify the accuracy of our results by comparing the areas of the pulmonary valve and pulmonary valve flap.