Roles of Integrin in Cardiovascular Diseases: From Basic Research to Clinical Implications.

Cardiovascular diseases (CVDs) pose a significant global health threat due to their complex pathogenesis and high incidence, imposing a substantial burden on global healthcare systems. Integrins, a group of heterodimers consisting of α and ß subunits that are located on the cell membrane, have emerged as key players in mediating the occurrence and progression of CVDs by regulating the physiological activities of endothelial cells, vascular smooth muscle cells, platelets, fibroblasts, cardiomyocytes, and various immune cells. The crucial role of integrins in the progression of CVDs has valuable implications for targeted therapies. In this context, the development and application of various integrin antibodies and antagonists have been explored for antiplatelet therapy and anti-inflammatory-mediated tissue damage. Additionally, the rise of nanomedicine has enhanced the specificity and bioavailability of precision therapy targeting integrins. Nevertheless, the complexity of the pathogenesis of CVDs presents tremendous challenges for monoclonal targeted treatment. This paper reviews the mechanisms of integrins in the development of atherosclerosis, cardiac fibrosis, hypertension, and arrhythmias, which may pave the way for future innovations in the diagnosis and treatment of CVDs.

Uncertainty and Irreproducibility of Triboelectricity Based on Interface Mechanochemistry.

Triboelectrification mechanism is still not understood, despite centuries of investigations. Here, we propose a model showing that mechanochemistry is key to elucidate triboelectrification fundamental properties. Studying contact between gold and silicate glasses, we observe that the experimental triboelectric output is subject to large variations and polarity inversions. First principles analysis shows that electronic transfer is activated by mechanochemistry and the tribopolarity is determined by the termination exposed to contact, depending on the material composition, which can result in different charging at the macroscale. The electron transfer mechanism is driven by the interface barrier dynamics, regulated by mechanical forces. The model provides a unified framework to explain several experimental observations, including the systematic variations in the triboelectric output and the mixed positive-negative "mosaic" charging patterns, and paves the way to the theoretical prediction of the triboelectric properties.

Biomaterial scaffolds regulate macrophage activity to accelerate bone regeneration.

Bones are important for maintaining motor function and providing support for internal organs. Bone diseases can impose a heavy burden on individuals and society. Although bone has a certain ability to repair itself, it is often difficult to repair itself alone when faced with critical-sized defects, such as severe trauma, surgery, or tumors. There is still a heavy reliance on metal implants and autologous or allogeneic bone grafts for bone defects that are difficult to self-heal. However, these grafts still have problems that are difficult to circumvent, such as metal implants that may require secondary surgical removal, lack of bone graft donors, and immune rejection. The rapid advance in tissue engineering and a better comprehension of the physiological mechanisms of bone regeneration have led to a new focus on promoting endogenous bone self-regeneration through the use of biomaterials as the medium. Although bone regeneration involves a variety of cells and signaling factors, and these complex signaling pathways and mechanisms of interaction have not been fully understood, macrophages undoubtedly play an essential role in bone regeneration. This review summarizes the design strategies that need to be considered for biomaterials to regulate macrophage function in bone regeneration. Subsequently, this review provides an overview of therapeutic strategies for biomaterials to intervene in all stages of bone regeneration by regulating macrophages.

Physical Origin of the Mechanochemical Coupling at Interfaces.

We used density functional theory calculations to investigate the physical origin of the mechanochemical response of material interfaces. Our results show that the mechanochemical response can be decomposed into the contribution from the interface itself (deformation of interfacial bonds) and a contribution from the underlying solid. The relative contributions depend on the stiffness of these regions and the contact geometry, which affects the stress distribution within the bulk region. We demonstrate that, contrary to what is commonly assumed, the contribution to the activation volume from the elastic deformation of the surrounding bulk is significant and, in some case, may be dominant. We also show that the activation volume and the mechanochemical response of interfaces should be finite due to the effects on the stiffness and stress distribution within the near-surface bulk region. Our results indicate that the large range of activation volumes measured in the previous experiments even for the same material system might originate from the different degrees of contributions probed from the bulk vs interface.

Soil heavy metal pollution and food safety in China: Effects, sources and removing technology.

Soil plays a fundamental role in food safety and the adverse effects of contaminants like heavy metal (loid)s on crop quality have threatened human health. Therefore, it is important to focus on the food safety and agricultural soil pollution by heavy metals, especially for China where the demand for food production is increasing. This review comprehensively introduced the current status of agricultural soil pollution by heavy metals in China, analyzed the main sources of contaminants, including the applications of pesticides and fertilizers, atmospheric deposition related to vehicle emissions and coal combustion, sewage irrigation and mining. Food safety and agricultural soil pollution by heavy metals, the removal technologies for soil remediation such as soil amendments, phytoremediation and foliar sprays were also introduced. The review can provide significant insights for policymakers, environmental engineers, and agro-technicians regarding soil contamination control and management strategies and technologies.

Linear Aging Behavior at Short Timescales in Nanoscale Contacts.

Nanoscale silica-silica contacts were recently found to exhibit logarithmic aging for times ranging from 0.1 to 100 s, consistent with the macroscopic rate and state friction laws and several other aging processes. Nanoscale aging in this system is attributed to progressive formation of interfacial siloxane bonds between surface silanol groups. However, understanding or even data for contact behavior for aging times <0.1 s, before the onset of logarithmic aging, is limited. Using a combination of atomic force microscopy experiments and kinetic Monte Carlo simulations, we find that aging is nearly linear with aging time at short timescales between ∼ 5 and 90 ms. We demonstrate that aging at these timescales requires the existence of a particular range of reaction energy barriers for interfacial bonding. Specifically, linear aging behavior consistent with experiments requires a narrow peak close to the upper bound of this range of barriers. These new insights into the reaction kinetics of interfacial bonding in nanoscale aging advance the development of physically based rate and state friction laws for nanoscale contacts.

Memory Distance for Interfacial Chemical Bond-Induced Friction at the Nanoscale.

Macroscale rate and state friction (RSF) laws include a memory distance, Dc, which is considered to be the distance required for a population of frictional contacts to renew itself via slip, counteracting the effects of aging in slow or static contact. This concept connects static friction and kinetic friction. Here, we use atomic force microscopy to study interfacial chemical bond-induced kinetic friction and the memory distance at the nanoscale for single silica-silica nanocontacts. We observe a logarithmic trend of decreasing friction with sliding velocity (i.e., velocity-weakening) at low velocities and a transition to increasing friction with velocity at higher velocities (i.e., velocity-strengthening). We propose a physically based kinetic model for the nanoscale memory effect, the "activation-passivation loop" model, which accounts for the activation and passivation of chemical reaction sites and the formation of new chemical bonds from dangling bonds during sliding. In the model, we define the memory distance to be the average sliding distance that accrues before an activated reaction site becomes passivated. Results from numerical simulations based on this model match experimental friction data well in the velocity-weakening regime and show that Dc is sensitive to the surface chemistry, and nearly independent of sliding velocity. The simulations also show values of Dc that are consistent with those obtained from the experiments. We propose a semiquantitative physical explanation of the observed logarithmic velocity-weakening behavior based on the conservation of the number of interfacial bonds during sliding. We also extract from the experimental data physically reasonable values of the energy barriers to the activation of reaction sites. Our results provide one possible physical mechanism for the nanoscale memory distance.

Inhibiting c-Jun N-terminal kinase (JNK)-mediated apoptotic signaling pathway in PC12 cells by a polysaccharide (CCP) from Coptis chinensis against Amyloid-ß (Aß)-induced neurotoxicity.

In this study, we investigated the protective effect and possible mechanism of a polysaccharide (CCP) from Coptis chinensis against Amyloid-ß protein (Aß)-induced toxicity in PC12 cells. The results showed pretreatment with CCP significantly protected PC12 cells from Aß25-35 induced cell death, lactate dehydrogenase (LDH) release, nuclear fragmentation, mitochondrial dysfunction and cytochrome c release from mitochondria. Furthermore, CCP (100 µg/ml) significantly inhibited Aß25-35 induced c-Jun N-terminal kinase (JNK) phosphorylation, but not influence signal-regulated kinase (ERK) and P38 mitogen-activated protein kinase (p38MAPK) pathway, and interestingly, the promoting effect of CCP on PC12 cell survival was only blocked by pre-treatment with a SP600125 (JNK inhibitor). In addition, Aß25-35-induced increase of Bax and cleaved caspase-3, as well as decrease of Bcl-2 protein expression was markedly reversed by CCP or SP600125. Thus, our results indicate that the neuroprotective effect of CCP is associated with JNK-dependent apoptotic pathway.

Chemical aging of large-scale randomly rough frictional contacts.

It has been shown that contact aging due to chemical reactions in single asperity contacts can have a significant effect on friction. However, it is currently unknown how chemically induced contact aging of friction depends on roughness that is typically encountered in macroscopic rough contacts. Here we develop an approach that brings together a kinetic Monte Carlo model of chemical aging with a contact mechanics model of rough surfaces based on the boundary element method to determine the magnitude of chemical aging in silica-silica contacts with random roughness. Our multiscale model predicts that chemical aging for randomly rough contacts has a logarithmic dependence on time. It also shows that friction aging switches from a linear to a nonlinear dependence on the applied load as the load increase. We discover that surface roughness affects the aging behavior primarily by modifying the real contact area and the local contact pressure, whereas the effect of contact morphology is relatively small. Our results demonstrate how understanding of chemical aging can be translated from studies of single asperity contacts to macroscopic rough contacts.

Neuroprotective effects of Coptis chinensis Franch polysaccharide on amyloid-beta (Aß)-induced toxicity in a transgenic Caenorhabditis elegans model of Alzheimer's disease (AD).

This study aims to investigate the neuroprotective effects of Coptis chinensis Franch polysaccharide (CCP) on Aß1-42 transgenic CL4176 Caenorhabditis elegans, as well as its mechanism of action. The results in life span experiment showed that CCP could significantly increase the lifespan of C. elegans and the effect is in the descending order of 100mg/L>500mg/L>200mg/L. The behavioral experiments also demonstrated that CCP at the concentration of 100mg/L could delay the paralysis rate of C. elegans, which was significantly different from the control group. In terms of Aß toxicity in C. elegans, morphological observation using Thioflavin S staining method indicated that the deposition of Aß protein in the head area of the untreated C. elegans was much more than those in the CCP (100mg/L)-treated CL4176. In line with this finding, fluorogenic quantitative real-time PCR confirmed that the transcriptional levels of HSP16.2 (Y46H3A.D) and HSP16.41 (Y46H3A.E) in C. elegans was 21 times and 79 times higher than those in untreated control. Thus, these data demonstrate that CCP could reduce Aß-induced toxicity by delaying the aging, decreasing the rate of paralysis, inhibiting the deposition of Aß, and increasing the expression levels of HSP genes in transgenic C. elegans.