Macrophages modulate stiffness-related foreign body responses through plasma membrane deformation.

Implants are widely used in medical applications and yet macrophage-mediated foreign body reactions caused by implants severely impact their therapeutic effects. Although the extensive use of multiple surface modifications has been introduced to provide some mitigation of fibrosis, little is known about how macrophages recognize the stiffness of the implant and thus influence cell behaviors. Here, we demonstrated that macrophage stiffness sensing leads to differential inflammatory activation, resulting in different degrees of fibrosis. The potential mechanism for macrophage stiffness sensing in the early adhesion stages tends to involve cell membrane deformations on substrates with different stiffnesses. Combining theory and experiments, we show that macrophages exert traction stress on the substrate through adhesion and altered membrane curvature, leading to the uneven distribution of the curvature-sensing protein Baiap2, resulting in cytoskeleton remodeling and inflammation inhibition. This study introduces a physical model feedback mechanism for early cellular stiffness sensing based on cell membrane deformation, offering perspectives for future material design and targeted therapies.

Altered white matter functional pathways in Alzheimer's disease.

Alzheimer's disease (AD) is associated with functional disruption in gray matter (GM) and structural damage to white matter (WM), but the relationship to functional signal in WM is unknown. We performed the functional connectivity (FC) and graph theory analysis to investigate abnormalities of WM and GM functional networks and corpus callosum among different stages of AD from a publicly available dataset. Compared to the controls, AD group showed significantly decreased FC between the deep WM functional network (WM-FN) and the splenium of corpus callosum, between the sensorimotor/occipital WM-FN and GM visual network, but increased FC between the deep WM-FN and the GM sensorimotor network. In the clinical groups, the global assortativity, modular interaction between occipital WM-FN and visual network, nodal betweenness centrality, degree centrality, and nodal clustering coefficient in WM- and GM-FNs were reduced. However, modular interaction between deep WM-FN and sensorimotor network, and participation coefficients of deep WM-FN and splenium of corpus callosum were increased. These findings revealed the abnormal integration of functional networks in different stages of AD from a novel WM-FNs perspective. The abnormalities of WM functional pathways connect downward to the corpus callosum and upward to the GM are correlated with AD.

Corticostriatal causality analysis in children and adolescents with attention-deficit/hyperactivity disorder.

AIM: The effective connectivity between the striatum and cerebral cortex has not been fully investigated in attention-deficit/hyperactivity disorder (ADHD). Our objective was to explore the interaction effects between diagnosis and age on disrupted corticostriatal effective connectivity and to represent the modulation function of altered connectivity pathways in children and adolescents with ADHD. METHODS: We performed Granger causality analysis on 300 participants from a publicly available Attention-Deficit/Hyperactivity Disorder-200 dataset. By computing the correlation coefficients between causal connections between striatal subregions and other cortical regions, we estimated the striatal inflow and outflow connection to represent intermodulation mechanisms in corticostriatal pathways. RESULTS: Interactions between diagnosis and age were detected in the superior occipital gyrus within the visual network, medial prefrontal cortex, posterior cingulate gyrus, and inferior parietal lobule within the default mode network, which is positively correlated with hyperactivity/impulsivity severity in ADHD. Main effect of diagnosis exhibited a general higher cortico-striatal causal connectivity involving default mode network, frontoparietal network and somatomotor network in ADHD compared with comparisons. Results from high-order effective connectivity exhibited a disrupted information pathway involving the default mode-striatum-somatomotor-striatum-frontoparietal networks in ADHD. CONCLUSION: The interactions detected in the visual-striatum-default mode networks pathway appears to be related to the potential distraction caused by long-term abnormal information input from the retina in ADHD. Higher causal connectivity and weakened intermodulation may indicate the pathophysiological process that distractions lead to the impairment of motion planning function and the inhibition/control of this unplanned motion signals in ADHD.

The Effects Analysis of Contact Stiffness of Double-Row Tapered Roller Bearing under Composite Loads.

Double-row tapered roller bearings have been widely used in various equipment recently due to their compact structure and ability to withstand large loads. The dynamic stiffness is composed of contact stiffness, oil film stiffness and support stiffness, and the contact stiffness has the most significant influence on the dynamic performance of the bearing. There are few studies on the contact stiffness of double-row tapered roller bearings. Firstly, the contact mechanics calculation model of double-row tapered roller bearing under composite loads has been established. On this basis, the influence of load distribution of double-row tapered roller bearing is analyzed, and the calculation model of contact stiffness of double-row tapered roller bearing is obtained according to the relationship between overall stiffness and local stiffness of bearing. Based on the established stiffness model, the influence of different working conditions on the contact stiffness of the bearing is simulated and analyzed, and the effects of radial load, axial load, bending moment load, speed, preload, and deflection angle on the contact stiffness of double row tapered roller bearings have been revealed. Finally, by comparing the results with Adams simulation results, the error is within 8%, which verifies the validity and accuracy of the proposed model and method. The research content of this paper provides theoretical support for the design of double-row tapered roller bearings and the identification of bearing performance parameters under complex loads.

Mediation of JA signalling in glandular trichomes by the woolly/SlMYC1 regulatory module improves pest resistance in tomato.

Almost all plants form trichomes, which protect them against insect herbivores by forming a physical barrier and releasing chemical repellents. Glandular trichomes produce a variety of specialized defensive metabolites, including volatile terpenes. Previous studies have shown that the defence hormone jasmonic acid (JA) affects trichome development and induces terpene synthases (TPSs) but the underlying molecular mechanisms remain unclear. Here, we characterized a loss-of-function allele of the HD-ZIP IV transcription factor woolly (wo) and analysed its role in mediating JA signalling in tomato. We showed that knockout of wo led to extensive trichome defects, including structural and functional changes in type VI glandular trichomes, and a dramatic reduction in terpene levels. We further found that wo directly binds to TPS gene promoters to recruit SlMYC1, a JA signalling modulator, and that together these transcription factors promote terpene biosynthesis in tomato trichomes. The wo/SlMYC1 regulatory module is inhibited by SlJAZ2 through a competitive binding mechanism, resulting in a fine-tuned JA response in tomato trichomes. Enhanced expression of SlMYC1 substantially increased terpene levels and improved tomato resistance to spider mites. Interestingly, we also found that SlMYC1 plays an additional role in glandular cell division and expansion in type VI trichomes, independent of JA. Together, our results reveal a novel, JA-mediated regulatory mechanism that promotes insect resistance in tomato.

Pickering emulsions stabilized by metal-organic frameworks, graphitic carbon nitride and graphene oxide.

Pickering emulsion is a heterogeneous system consisting of at least two immiscible liquids, which are stabilized by solid particles, in which organic solvent or water is dispersed into other phase in form of micrometre-sized droplets. Compared to traditional emulsions stabilized by surfactant, solids are cheap and can be easily separated and recycled by centrifugation or filtration after use. Moreover, the properties of Pickering emulsions can be adjusted by using different types of solid particles. Up to now, Pickering emulsions have been applied in a wide range of areas such as material science and catalysis. Here we review recent studies on Pickering emulsions stabilized by metal-organic framework, graphitic carbon nitride and graphene oxide.

Highly Electrocatalytic Ethylene Production from CO2 on Nanodefective Cu Nanosheets.

The electrochemical synthesis of chemicals from carbon dioxide, which is an easily available and renewable carbon resource, is of great importance. However, to achieve high product selectivity for desirable C2 products like ethylene is a big challenge. Here we design Cu nanosheets with nanoscaled defects (2-14 nm) for the electrochemical production of ethylene from carbon dioxide. A high ethylene Faradaic efficiency of 83.2% is achieved. It is proved that the nanoscaled defects can enrich the reaction intermediates and hydroxyl ions on the electrocatalyst, thus promoting C-C coupling for ethylene formation.

Converting Metal-Organic Framework Particles from Hydrophilic to Hydrophobic by an Interfacial Assembling Route.

Here, we propose to modify the hydrophilicity of metal-organic framework (MOF) particles by an interfacial assembling route, which is based on the surface-active nature of MOF particles. It was found that hydrophilic UiO-66-NH2 particles can be converted to hydrophobic particles through an oil-water interfacial assembling route. The underlying mechanism for the conversion of UiO-66-NH2 was investigated by X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy. It was revealed that the close assembly of UiO-66-NH2 particles at the oil-water interface strengthens the coordination between organic ligands and metal ions, which results in a decrease in the proportion of hydrophilic groups on UiO-66-NH2 particle surfaces. Hydrophobic UiO-66-NH2 particles show improved adsorption capacity for dyes in organic solvents compared with pristine UiO-66-NH2 particles. It is expected that the interfacial assembling route can be applied to the synthesis of different kinds of MOF materials with tunable hydrophilicity or hydrophobicity required for diverse applications.

Pickering emulsions stabilized by a metal-organic framework (MOF) and graphene oxide (GO) for producing MOF/GO composites.

Herein we demonstrate the formation of a novel kind of Pickering emulsion that is stabilized by a Zr-based metal-organic framework (Zr-MOF) and graphene oxide (GO). It was found that the Zr-BDC-NO2 and GO solids assembling at the oil/water interface can effectively stabilize the oil droplets that are dispersed in the water phase. Such a Pickering emulsion offers a facile route for fabricating Zr-MOF/GO composite materials. After removing water and oil by freeze drying from Pickering emulsions, the Zr-MOF/GO composites were obtained and their morphologies, structures and interaction properties were characterized by scanning electron microscopy, transmission electron microscopy, X-ray diffraction and Fourier transform infrared spectrometry, respectively. The influences of the concentration of GO and Zr-MOF on the emulsion microstructures and the properties of the MOF/GO composites were studied. Based on experimental results, the mechanisms for the emulsion formation by Zr-MOF and GO and the as-synthesized superstructures of the Zr-MOF/GO composite were proposed. It is expected that this facile and tunable route can be applied to the synthesis of different kinds of MOF-based or GO-based composite materials.

Interfacial assembly and hydrolysis for synthesizing a TiO2/metal-organic framework composite.

Herein we propose an interfacial assembly and hydrolysis route for fabricating TiO2/UiO-67 composites. The UiO-67 assembles at the water-oil interface serving as a stabilizer of the emulsion. TiO2 nanoparticles are loaded on UiO-67 by hydrolysis of the precursor TBT (tetra-n-butyl titanate) at the water-oil interface. By such a strategy, hollow capsules structured by UiO-67 and decorated by ultra-small TiO2 nanoparticles were produced. The newly-constructed composite combines the CO2 adsorption properties of UiO-67 and the photocatalytic activity of TiO2, showing high activity for the photocatalytic reduction of CO2 to formic acid. Such a composite with a novel structure provides a promising route for the preparation of new compound materials.

Autophagic degradation of DHCR7 activates AKT3 and promotes sevoflurane-induced hippocampal neuroinflammation in neonatal mice.

Repeated sevoflurane exposure in neonatal mice triggers neuroinflammation with detrimental effects on cognitive function. Yet, the mechanism of the sevoflurane-induced cytokine response is largely unknown. In this study, we reveal that 3-MA, an autophagy inhibitor, attenuated the sevoflurane-induced neuroinflammation and cognitive dysfunction, including the decreased freezing time and fewer platform crossings, in the neonate mice. 3-Methyladenine (3-MA) suppressed sevoflurane-induced expression of interleukin-6 and tumor necrosis factor-alpha in vitro. Moreover, sevoflurane activates IRF3, facilitating cytokine transcription in an AKT3-dependent manner. Mechanistically, sevoflurane-induced autophagic degradation of dehydrocholesterol-reductase-7 (DHCR7) resulted in accumulations of its substrate 7-dehydrocholesterol (7-DHC), mimicking the effect of sevoflurane on AKT3 activation and IRF3-driven cytokine expression. 3-MA significantly reversed sevoflurane-induced DHCR7 degradation, AKT phosphorylation, IRF3 activation, and the accumulation of 7-DHC in the hippocampal CA1 region. These findings pave the way for additional investigations aimed at developing novel strategies to mitigate postoperative cognitive impairment in pediatric patients.

Bcl-xL mediates interferon-beta secretion by protease-activated receptor 2 deficiency through the mitochondrial permeability transition pore in colorectal cancer metastasis.

Cellular plasticity and immune escape are synergistic drivers of tumor colonization in metastatic organs. Activation of protease-activated receptor 2 (PAR2) signaling promotes metastasis of colorectal carcinoma (CRC). The role of PAR2 in regulating the immune microenvironment and cancer progression remains unclear. We demonstrated that the regulation of liver metastasis by PAR2 requires a competent immune system. PAR2 knockdown enhanced liver infiltration of activated CD8+ T cells prior to metastatic foci formation in an interferon receptor-dependent manner. PAR2 depletion increased interferon (IFN)-ß production via the cGAS-STING and RIG-1 pathways. PAR2 inhibition increased mitochondrial permeability and cytosolic accumulation of mitochondrial DNA, which was reversed by Bcl-xL expression. Strikingly, shRNA against PAR2 with an immune checkpoint blocker (ICB) acted synergistically to suppress liver metastasis. Analysis of single-cell sequence data and 24 paired samples confirmed the regulatory effect of PAR2 on the metastatic immune environment in human CRC. Therefore, PAR2 signaling is involved in stabilizing the mitochondrial membrane and regulating the immune microenvironment through IFN-ß during liver metastasis in CRC. The synergistic effect of the PAR2 inhibitor and ICB provides a potential therapeutic strategy for metastatic CRC treatment.

Whole-brain structure-function coupling abnormalities in mild cognitive impairment: a study combining amplitude of low-frequency fluctuations and voxel-based morphometry.

Alzheimer's disease (AD), one of the leading diseases of the nervous system, is accompanied by symptoms such as loss of memory, thinking and language skills. Both mild cognitive impairment (MCI) and very mild cognitive impairment (VMCI) are the transitional pathological stages between normal aging and AD. While the changes in whole-brain structural and functional information have been extensively investigated in AD, The impaired structure-function coupling remains unknown. The current study employed the OASIS-3 dataset, which includes 53 MCI, 90 VMCI, and 100 Age-, gender-, and education-matched normal controls (NC). Several structural and functional parameters, such as the amplitude of low-frequency fluctuations (ALFF), voxel-based morphometry (VBM), and The ALFF/VBM ratio, were used To estimate The whole-brain neuroimaging changes In MCI, VMCI, and NC. As disease symptoms became more severe, these regions, distributed in the frontal-inf-orb, putamen, and paracentral lobule in the white matter (WM), exhibited progressively increasing ALFF (ALFFNC < ALFFVMCI < ALFFMCI), which was similar to the tendency for The cerebellum and putamen in the gray matter (GM). Additionally, as symptoms worsened in AD, the cuneus/frontal lobe in the WM and the parahippocampal gyrus/hippocampus in the GM showed progressively decreasing structure-function coupling. As the typical focal areas in AD, The parahippocampal gyrus and hippocampus showed significant positive correlations with the severity of cognitive impairment, suggesting the important applications of the ALFF/VBM ratio in brain disorders. On the other hand, these findings from WM functional signals provided a novel perspective for understanding the pathophysiological mechanisms involved In cognitive decline in AD.

Ultrasound-Induced Gold Nanoparticle United with Acoustic Reprogramming of Macrophages for Enhanced Cancer Therapy.

Sonodynamic therapy (SDT) has considerable potential in cancer treatment and exhibits high tissue penetration with minimal damage to healthy tissues. The efficiency of SDT is constrained by the complex immunological environment and tumor treatment resistance. Herein, a specific acoustic-actuated tumor-targeted nanomachine is proposed to generate mechanical damage to lysosomes for cancer SDT. The hybrid nanomachine was assembled with gold nanoparticles (GNPs) as the core and encapsulated with macrophage exosomes modified by AS1411 aptamers (GNP@EXO-APs) to optimize the pharmacokinetics and tumor aggregation. GNP@EXO-APs could be specifically transferred to the lysosomes of tumor cells. After induction with ultrasound, GNP@EXO-APs generated strong mechanical stress to produce lysosomal-dependent cell death in cancer cells. Notably, tumor-associated macrophages were reprogrammed in the ultrasound environment to an antitumor phenotype. Enhanced mechanical destruction via GNP@EXO-APs and immunotherapy of cancer cells were verified both in vitro and in vivo under SDT. This study provides a new direction for inside-out killing effects on tumor cells for cancer treatment.

Oxidation of metallic Cu by supercritical CO2 and control synthesis of amorphous nano-metal catalysts for CO2 electroreduction.

Amorphous nano-metal catalysts often exhibit appealing catalytic properties, because the intrinsic linear scaling relationship can be broken. However, accurate control synthesis of amorphous nano-metal catalysts with desired size and morphology is a challenge. In this work, we discover that Cu(0) could be oxidized to amorphous CuxO species by supercritical CO2. The formation process of the amorphous CuxO is elucidated with the aid of machine learning. Based on this finding, a method to prepare Cu nanoparticles with an amorphous shell is proposed by supercritical CO2 treatment followed by electroreduction. The unique feature of this method is that the size of the particles with amorphous shell can be easily controlled because their size depends on that of the original crystal Cu nanoparticles. Moreover, the thickness of the amorphous shell can be easily controlled by CO2 pressure and/or treatment time. The obtained amorphous Cu shell exhibits high selectivity for C2+ products with the Faradaic efficiency of 84% and current density of 320 mA cm-2. Especially, the FE of C2+ oxygenates can reach up to 65.3 %, which is different obviously from the crystalline Cu catalysts.

The Willingness of the Elderly to Choose Nursing Care: Evidence From in China.

With the accelerating aging of the population and the worsening psychological conditions of older people, the traditional mode of family support for the elderly in China does not always meet the physical and psychological needs of the elderly, and more social support modes for the elderly are needed. Based on 3,513 valid questionnaires on the long-term care and protection needs of Chinese residents, this paper uses a logit regression model to analyze the factors influencing the willingness of the elderly to choose nursing care. The results show that intergenerational family support for the elderly is a significant psychological driver on the willingness of the elderly to choose nursing care. Compared with the elderly living with family, empty nesters or older people living alone are more inclined to select nursing care when they have difficulties taking care of themselves. The physical health of the elderly affects their willingness to choose nursing care, and elderly individuals with more hospitalizations are less likely to select nursing care. In addition, elderly females who are relatively young, have a high level of education, have a high income, have a nursing home near the residence, and are already covered by medical insurance are more willing to choose nursing care. The results of this study are of great importance for improving the medical services and aging care services for the elderly and providing theoretical support for alleviating the psychological and social pressure brought by population aging.

Low Surface Accessible Area NanoCoral TiO2 for the Reduction of Foreign Body Reaction During Implantation.

The entry of implants triggers the secretion of damage associated molecular patterns (DAMPs) that recruit dendritic cells (DCs) and results in subsequent foreign body reaction (FBR). Though several studies have illustrated that the surface accessible area (SAA) of implants plays a key role in the process of DAMPs release and absorption, the effect of SAA on the immune reaction still remains unknown. Here, a series of TiO2 plates with different SAA is fabricated to investigate the relationship between SAA and FBR. Compared with larger SAA surface, the aggregation of DC is significantly inhibited by lower SAA surface. Total internal reflection microscopy (TIRFM) and molecular dynamic (MD) simulation show that although high mobility group box 1 (HMGB1) is adsorbed more on plates with lower SAA, the exposure ratio of cysteine (CYS) residue in HMGB1 is significantly decreased in lower SAA group. The lower exposure of CYS reduces the activation of Toll-like receptors 4 (TLR4), which down-regulates the expression of myeloid differentiation factor (Myd88)-TNF receptor associated factor 6 (TRAF6) to inhibit nuclear factor kappa B (NF-κB) signaling. Generally, this study reveals the mechanism of how SAA, a nanoscale property, affects FBR from perspective of DAMPs, and provides a new direction for designing better biocompatible implants.

Oxygen Ion Implantation Improving Cell Adhesion on Titanium Surfaces through Increased Attraction of Fibronectin PHSRN Domain.

Mechanistic understanding of fibronectin (FN) adsorption which determines cell adhesion on cell-implant interfaces is significant for improving the osteoconduction and soft-tissue healing of implants. Here, it is shown that the adsorption behavior of FN on the titanium oxide surface (TiO2 ) is highly relative to its Pro-His-Ser-Arg-Asn (PHSRN) peptide. FN lacking PHSRN fails to bind to surfaces, resulting in inhibited cell adhesion and spreading. Molecular dynamics simulation shows higher affinity and greater adsorption energy of PHSRN peptide with TiO2 surface due to the stronger hydrogen bonds formed by the serine and arginine residues with O ion of the substrate. Finally, by increasing O content in TiO2 surfaces through O ion-beam implantation, improving the cell adhesion, cell differentiation, and the subsequent biomineralization on titanium implant is realized. This study reveals the vital role of PHSRN in FN-mediated cell adhesion on implant surfaces, providing a promising new target for further tissue integration and implant success.

Regional homogeneity abnormalities of resting state brain activities in children with growth hormone deficiency.

Growth hormone deficiency (GHD) is a common developmental disorder in children characterized by low levels of growth hormone secretion, short stature, and multiple cognitive and behavioral problems, including hyperactivity, anxiety, and depression. However, the pathophysiology of this disorder remains unclear. In order to investigate abnormalities of brain functioning in children with GHD, we preformed functional magnetic resonance imaging and regional homogeneity (ReHo) analysis in 26 children with GHD and 15 age- and sex-matched healthy controls (HCs) in a resting state. Compared with HCs, children with GHD exhibited increased ReHo in the left putamen and decreased ReHo in the right precentral gyrus, reflecting a dysfunction of inhibitory control. Decreased ReHo was also identified in the orbital parts of the bilateral superior frontal gyrus and the medial part of the left superior frontal gyrus, a finding that correlated with the inappropriate anxiety and depression that are observed in this patient population. Our results provide imaging evidence of potential pathophysiologic mechanisms for the cognitive and behavioral abnormalities of children with GHD.

Mutation of SlARC6 leads to tissue-specific defects in chloroplast development in tomato.

The proliferation and development of chloroplasts are important for maintaining the normal chloroplast population in plant tissues. Most studies have focused on chloroplast maintenance in leaves. In this study, we identified a spontaneous mutation in a tomato mutant named suffulta (su), in which the stems appeared albinic while the leaves remained normal. Map-based cloning showed that Su encodes a DnaJ heat shock protein that is a homolog of the Arabidopsis gene AtARC6, which is involved in chloroplast division. Knockdown and knockout of SlARC6 in wild-type tomato inhibit chloroplast division, indicating the conserved function of SlARC6. In su mutants, most mesophyll cells contain only one or two giant chloroplasts, while no chloroplasts are visible in 60% of stem cells, resulting in the albinic phenotype. Compared with mature tissues, the meristem of su mutants suggested that chloroplasts could partially divide in meristematic cells, suggesting the existence of an alternative mechanism in those dividing cells. Interestingly, the adaxial petiole cells of su mutants contain more chloroplasts than the abaxial cells. In addition, prolonged lighting can partially rescue the albinic phenotypes in su mutants, implying that light may promote SlACR6-independent chloroplast development. Our results verify the role of SlACR6 in chloroplast division in tomato and uncover the tissue-specific regulation of chloroplast development.