Interstitial Fluid Shear Stress Induces the Synthetic Phenotype Switching of VSMCs to Release Pro-calcified Extracellular Vesicles via EGFR-MAPK-KLF5 Pathway.

Phenotypic switching (from contractile to synthetic) of vascular smooth muscle cells (VSMCs) is essential in the progression of atherosclerosis. The damaged endothelium in the atherosclerotic artery exposes VSMCs to increased interstitial fluid shear stress (IFSS). However, the precise mechanisms by which increased IFSS influences VSMCs phenotypic switching are unrevealed. Here, we employed advanced numerical simulations to calculate IFSS values accurately based on parameters acquired from patient samples. We then carefully investigated the phenotypic switching and extracellular vesicles (EVs) secretion of VSMCs under various IFSS conditions. By employing a comprehensive set of approaches, we found that VSMCs exhibited synthetic phenotype upon atherosclerotic IFSS. This synthetic phenotype is the upstream regulator for the enhanced secretion of pro-calcified EVs. Mechanistically, as a mechanotransducer, the epidermal growth factor receptor (EGFR) initiates the flow-based mechanical cues to MAPK signaling pathway, facilitating the nuclear accumulation of the transcription factor krüppel-like factor 5 (KLF5). Furthermore, pharmacological inhibiting either EGFR or MAPK signaling pathway blocks the nuclear accumulation of KLF5 and finally results in the maintenance of contractile VSMCs even under increased IFSS stimulation. Collectively, targeting this signaling pathway holds potential as a novel therapeutic strategy to inhibit VSMCs phenotypic switching and mitigate the progression of atherosclerosis.

Reactive Oxygen Species-Responsive Nano-platform with Dual-Targeting and Fluorescent Lipid-Specific Imaging Capabilities for the management of Atherosclerotic Plaques.

Atherosclerosis (AS), a pathological cause of cardiovascular disease, results from endothelial injury, local progressive inflammation, and excessive lipid accumulation. AS plaques rich in foam cells are prone to rupture and form thrombus, which can cause life-threatening complications. Therefore, the assessment of atherosclerotic plaque vulnerability and early intervention are crucial in reducing the mortality rates associated with cardiovascular disease. In this work, A fluorescent probe FC-TPA was synthesized, which switches the fluorescence state between protonated and non-protonated, reducing background fluorescence and enhancing signal-to-noise ratio. On this basis, FC-TPA is loaded into cyclodextrin (CD) modified with phosphatidylserine targeting peptide (PTP) and coated with hyaluronic acid (HA) to construct the intelligent responsive diagnostic nanoplatform (HA@PCFT). HA@PCFT effectively targets atherosclerotic plaques, utilizing dual targeting mechanisms. HA binds strongly to CD44, while PTP binds to phosphatidylserine, enabling nanoparticle aggregation at the lesion site. ROS acts as a smart release switch for probes. Both in vitro and in vivo evaluations confirm impressive lipid-specific fluorescence imaging capabilities of HA@PCFT nanoparticles (NPs). The detection of lipid load in atherosclerotic plaque by fluorescence imaging will aid in assessing the vulnerability of atherosclerotic plaque. STATEMENT OF SIGNIFICANCE: Currently, numerous fluorescent probes have been developed for lipid imaging. However, some challenges including inadequate water solubility, nonspecific distribution patterns, and fluorescence background interference, have greatly limited their further applications in vivo. To overcome these limitations, a fluorescent molecule has been designed and synthesized, thoroughly investigating its photophysical properties through both theoretical and experimental approaches. Interestingly, this fluorescent molecule exhibits the reversible fluorescence switching capabilities, mediated by hydrogen bonds, which effectively mitigate background fluorescence interference. Additionally, the fluorescent molecules has been successfully loaded into nanocarriers functionalized with the active targeting abilities, which has significantly improved the solubility of the fluorescent molecules and reduced their nonspecific distribution in vivo for an efficient target imaging in atherosclerosis. This study provides a valuable reference for evaluating the performance of such fluorescent dyes, and offers a promising perspective on the design of the target delivery systems for atherosclerosis.

Impact of Probiotic Lactiplantibacillus plantarum ATCC 14917 on atherosclerotic plaque and its mechanism.

Atherosclerosis is viewed as not just as a problem of lipid build-up in blood vessels, but also as a chronic inflammatory disease involving both innate and acquired immunity. In atherosclerosis, the inflammation of the arterial walls is the key characteristic that significantly contributes to both the instability of plaque and the occlusion of arteries by blood clots. These events ultimately lead to stroke and acute coronary syndrome. Probiotics are living microorganisms that, when consumed in the right quantities, offer advantages for one's health. The primary objective of this study was to investigate the influence of Lactiplantibacillus plantarum ATCC 14917 (ATCC 14917) on the development of atherosclerotic plaques and its underlying mechanism in Apo lipoprotein E-knockout (Apoe-/- mice). In this study, Apoe-/- mice at approximately 8 weeks of age were randomly assigned to three groups: a Normal group that received a normal chow diet, a high fat diet group that received a gavage of PBS, and a Lactiplantibacillus plantarum ATCC 14917 group that received a high fat diet and a gavage of 0.2 ml ATCC 14917 (2 × 109 CFU/mL) per day for a duration of 12 weeks. Our strain effectively reduced the size of plaques in Apoe-/- mice by regulating the expression of inflammatory markers, immune cell markers, chemokines/chemokine receptors, and tight junction proteins (TJPs). Specifically, it decreased the levels of inflammatory markers (ICAM-1, CD-60 MCP-1, F4/80, ICAM-1, and VCAM-1) in the thoracic aorta, (Ccr7, cd11c, cd4, cd80, IL-1ß, TNF-α) in the colon, and increased the activity of ROS-scavenging enzymes (SOD-1 and SOD-2). It also influenced the expression of TJPs (occludin, ZO-1, claudin-3, and MUC-3). In addition, the treatment of ATCC 14917 significantly reduced the level of lipopolysaccharide in the mesenteric adipose tissue. The findings of our study demonstrated that our strain effectively decreased the size of atherosclerotic plaques by modulating inflammation, oxidative stress, intestinal integrity, and intestinal immunity.

Biomechanics-mediated endocytosis in atherosclerosis.

Biomechanical forces, including vascular shear stress, cyclic stretching, and extracellular matrix stiffness, which influence mechanosensitive channels in the plasma membrane, determine cell function in atherosclerosis. Being highly associated with the formation of atherosclerotic plaques, endocytosis is the key point in molecule and macromolecule trafficking, which plays an important role in lipid transportation. The process of endocytosis relies on the mobility and tension of the plasma membrane, which is sensitive to biomechanical forces. Several studies have advanced the signal transduction between endocytosis and biomechanics to elaborate the developmental role of atherosclerosis. Meanwhile, increased plaque growth also results in changes in the structure, composition and morphology of the coronary artery that contribute to the alteration of arterial biomechanics. These cross-links of biomechanics and endocytosis in atherosclerotic plaques play an important role in cell function, such as cell phenotype switching, foam cell formation, and lipoprotein transportation. We propose that biomechanical force activates the endocytosis of vascular cells and plays an important role in the development of atherosclerosis.

Preparation and characterization of chitosan/polyvinyl alcohol antibacterial sponge materials.

This study utilized the freeze-drying method to create a chitosan (CS) and polyvinyl alcohol (PVA) sponge. To enhance its antibacterial properties, curcumin and nano silver (Cur@Ag) were added for synergistic antibacterial. After adding curcumin and nano silver, the mechanical properties of the composite sponge dressing (CS-PVA-Cur@Ag) were improved. The porosity of the composite sponge dressing was closed to 80%, which was helpful for drug release, and it had good water absorption and water retention rate. The nano silver diameter was 50-80 nm, which was optimal for killing bacteria. Antibacterial tests usedEscherichia coliandStaphylococcus aureusdemonstrated that little nano silver was required to eliminate bacteria. Finally, in the rat full-thickness skin wound model, the composite sponge dressing can promote wound healing in a short time. In summary, CS-PVA-Cur@Ag wound dressing could protect from bacterial infection and accelerate wound healing. Thus, it had high potential application value for wound dressing.

Investigating the relationship between residual stress and micromechanical properties of blood vessels using atomic force microscopy.

The magnitude of vascular residual stress, an inherent characteristic exclusive to the vasculature, exhibits a strong correlation with vascular compliance, tensile resistance, vascular rigidity, and vascular remodeling subsequent to vascular transplantation. Vascular residual stress can be quantified by evaluating the magnitude of the opening angle within the vascular ring. For decellularized vessels, the vascular ring's opening angle diminishes, consequently reducing residual stress. The decellularization process induces a laxity in the vascular fiber structure within decellularized vessels. To investigate the interrelation between the magnitude of residual stress and the microstructure as well as mechanical properties of elastin and collagen within blood vessels, this study employed fresh blood vessels, stress-relieved vessels, and sections of decellularized blood vessels. Structural scanning and force map experiments on the surface of the sections were conducted using atomic force microscopy (AFM). The findings revealed well-organized arrangements of elastin and collagen within fresh vessels, wherein the regularity of collagen and elastin exhibited variability as residual stress declined. Furthermore, both stress-relieved and decellularized vessel sections exhibited a reduction in the mean Young's modulus to varying extents in comparison to fresh vessels. The validity of our experimental results was further corroborated through finite element simulations. Hence, residual stress assumes a crucial role in upholding the structural stability of blood vessels, and the intricate association between residual stress and the microstructural and micromechanical properties of blood vessels holds significant implications for comprehending the impact of vascular diseases on vascular structure and advancing the development of biomimetic artificial blood vessels that replicate residual stress. RESEARCH HIGHLIGHTS: In this inquiry, we scrutinized the interconnection amid vascular residual stress and the microscale and nanoscale aspects of vascular structure and mechanical function, employing AFM. We ascertained that residual stress assumes a pivotal role in upholding vascular microstructure and mechanical attributes. The experimental outcomes were subsequently validated through finite element simulation.

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Mechanobiology focuses on a series of important physiopathological processes, such as how cells perceive different mechanomechanical stimuli, the process of intracellular mechanotransduction, and how mechanical signals determine the behavior and fate of cells. From the initial stage of embryogenesis, to developmental biology and regenerative medicine, or even through the whole life process, mechanical signaling cascades and cellular mechanical responses in mechanobiology are of great significance in biomedical research. In recent years, research in the field of mechanobiology has undergone remarkable development. Several scientific consortia around the world have been analyzing mechanobiological processes from different perspectives, aiming to gain insights into the regulatory mechanisms by which mechanical factors affect cell fate determination. In this article, we summarized and reviewed the topics that have attracted more research interests in recent years in the field of mechanobiology, for example, arterial blood vessels, stem cell, and ion channel. We also discussed the potential trends that may emerge, such as nuclear deformation, fibrous extracellular matrix, tumor mechanobiology, cellular mechanotransduction, and piezo ion channels. In addition, we put forward new ideas concerning the limitations of mechanism research and the importance of big data analysis and mining in this field, thereby providing objective support and a systematic framework for grasping the hot research topics and exploring new research directions in the field of mechanobiology.

Hyaluronic acid-decorated curcumin-based coordination nanomedicine for enhancing the infected diabetic wound healing.

Persistent over-oxidation, inflammation and bacterial infection are the primary reasons for impaired wound repairing in diabetic patients. Therefore, crucial strategies to promote diabetic wound repairing involve suppressing the inflammatory response, inhibiting bacterial growth and decreasing reactive oxygen species (ROS) within the wound. In this work, we develop a multifunctional nanomedicine (HA@Cur/Cu) designed to facilitate the repairing process of diabetic wound. The findings demonstrated that the synthesized infinite coordination polymers (ICPs) was effective in enhancing the bioavailability of curcumin and improving the controlled drug release at the site of inflammation. Furthermore, in vitro and in vivo evaluation validate the capacity of HA@Cur/Cu to inhibit bacterial growth and remove excess ROS and inflammatory mediators, thereby significantly promoting the healing of diabetic wound in mice. These compelling findings strongly demonstrate the enormous promise of this multifunctional nanomedicine for the treatment of diabetic wound.

Analysis of bioprinting strategies for skin diseases and injuries through structural and temporal dynamics: historical perspectives, research hotspots, and emerging trends.

This study endeavors to investigate the progression, research focal points, and budding trends in the realm of skin bioprinting over the past decade from a structural and temporal dynamics standpoint. Scholarly articles on skin bioprinting were obtained from WoSCC. A series of bibliometric tools comprising R software, CiteSpace, HistCite, and an alluvial generator were employed to discern historical characteristics, evolution of active topics, and upcoming tendencies in the area of skin bioprinting. Over the past decade, there has been a consistent rise in research interest in skin bioprinting, accompanied by an extensive array of meaningful scientific collaborations. Concurrently, diverse dynamic topics have emerged during various periods, as substantiated by an aggregate of 22 disciplines, 74 keywords, and 187 references demonstrating citation bursts. Four burgeoning research subfields were discerned through keyword clustering-namely, #3 'in situbioprinting', #6 'vascular', #7 'xanthan gum', and #8 'collagen hydrogels'. The keyword alluvial map reveals that Module 1, including 'transplantation' etc, has primarily dominated the research module over the previous decade, maintaining enduring relevance despite annual shifts in keyword focus. Additionally, we mapped out the top six key modules from 2023 being 'silk fibroin nanofiber', 'system', 'ionic liquid', 'mechanism', and 'foot ulcer'. Three recent research subdivisions were identified via timeline visualization of references, particularly Clusters #0 'wound healing', #4 'situ mineralization', and #5 '3D bioprinter'. Insights derived from bibliometric analyses illustrate present conditions and trends in skin bioprinting research, potentially aiding researchers in pinpointing central themes and pioneering novel investigative approaches in this field.

Role of the intestinal microbiome and its therapeutic intervention in cardiovascular disorder.

The gut microbiome is a heterogeneous population of microbes comprising viruses, bacteria, fungi, and protozoa. Such a microbiome is essential for sustaining host equilibrium, and its impact on human health can be altered by a variety of factors such as external variables, social behavior, age, nutrition, and genetics. Gut microbes' imbalances are related to a variety of chronic diseases including cancer, obesity, and digestive disorders. Globally, recent findings show that intestinal microbes have a significant role in the formation of cardiovascular disease (CVD), which is still the primary cause of fatalities. Atherosclerosis, hypertension, diabetes, inflammation, and some inherited variables are all cardiovascular risk variables. However, studies found correlations between metabolism, intestinal flora, and dietary intake. Variations in the diversity of gut microbes and changes in their activity are thought to influence CVD etiology. Furthermore, the gut microbiota acts as an endocrine organ, producing bioactive metabolites such as TMA (trimethylamine)/TMAO (trimethylamine N-oxide), SCFA (short-chain fatty acids), and bile acids, which have a substantial impact on host wellness and disease by multiple mechanisms. The purpose of this overview is to compile current evidence highlighting the intricate links between gut microbiota, metabolites, and the development of CVD. It focuses on how intestinal dysbiosis promotes CVD risk factors such as heart failure, hypertension, and atherosclerosis. This review explores the normal physiology of intestinal microbes and potential techniques for targeting gut bacteria for CVD treatment using various microbial metabolites. It also examines the significance of gut bacteria in disease treatment, including supplements, prebiotics, probiotics, antibiotic therapies, and fecal transplantation, which is an innovative approach to the management of CVD. As a result, gut bacteria and metabolic pathways become increasingly attractive as potential targets for CVD intervention.

Mood and microbes: a comprehensive review of intestinal microbiota's impact on depression.

Depression is considered a multifaceted and intricate mental disorder of growing concern due to its significant impact on global health issues. The human gut microbiota, also known as the "second brain," has an important role in the CNS by regulating it through chemical, immunological, hormonal, and neurological processes. Various studies have found a significant bidirectional link between the brain and the gut, emphasizing the onset of depression therapies. The biological and molecular processes underlying depression and microbiota are required, as the bidirectional association may represent a novel study. However, profound insights into the stratification and diversity of the gut microbiota are still uncommon. This article investigates the emerging evidence of a bacterial relationship between the gut and the brain's neurological system and its potential pathogenicity and relevance. The interplay of microbiota, immune system, nervous system neurotransmitter synthesis, and neuroplasticity transitions is also widely studied. The consequences of stress, dietary fibers, probiotics, prebiotics, and antibiotics on the GB axis are being studied. Multiple studies revealed the processes underlying this axis and led to the development of effective microbiota-based drugs for both prevention and treatment. Therefore, the results support the hypothesis that gut microbiota influences depression and provide a promising area of research for an improved knowledge of the etiology of the disease and future therapies.

Fluid shear stress induced-endothelial phenotypic transition contributes to cerebral ischemia-reperfusion injury and repair.

Long-term ischemia leads to insufficient cerebral microvascular perfusion and dysfunction. Reperfusion restores physiological fluid shear stress (FSS) but leads to serious injury. The mechanism underlying FSS-induced endothelial injury in ischemia-reperfusion injury (IRI) remains poorly understood. In this study, a rat model of middle cerebral artery occlusion was constructed to explore cerebrovascular endothelial function and inflammation in vivo. Additionally, the rat brain microvascular endothelial cells (rBMECs) were exposed to a laminar FSS of 0.5 dyn/cm2 for 6 h and subsequently restored to physiological fluid shear stress level (2 dyn/cm2) for 2 and 12 h, respectively. We found that reperfusion induced endothelial-to-mesenchymal transition (EndMT) in endothelial cells, leading to serious blood-brain barrier dysfunction and endothelial inflammation, accompanied by the nuclear accumulation of Yes-associated protein (YAP). During the later stage of reperfusion, cerebral endothelium was restored to the endothelial phenotype with a distinct change in mesenchymal-to-endothelial transition (MEndT), while YAP was translocated and phosphorylated in the cytoplasm. Knockdown of YAP or inhibition of actin polymerization markedly impaired the EndMT in rBMECs. These findings suggest that ischemia-reperfusion increased intensity of FSS triggered an EndMT process and, thus, led to endothelial inflammation and tissue injury, whereas continuous FSS induced a time-dependent reversal MEndT event contributing to the endothelial repair. This study provides valuable insight for therapeutic strategies targeting IRI.

Structural and temporal dynamics analysis of zinc-based biomaterials: History, research hotspots and emerging trends.

Objectives: To examine the 16-year developmental history, research hotspots, and emerging trends of zinc-based biodegradable metallic materials from the perspective of structural and temporal dynamics. Methods: The literature on zinc-based biodegradable metallic materials in WoSCC was searched. Historical characteristics, the evolution of active topics and development trends in the field of zinc-based biodegradable metallic materials were analyzed using the bibliometric tools CiteSpace and HistCite. Results: Over the past 16 years, the field of zinc-based biodegradable metal materials has remained in a hotspot stage, with extensive scientific collaboration. In addition, there are 45 subject categories and 51 keywords in different research periods, and 80 papers experience citation bursts. Keyword clustering anchored 3 emerging research subfields, namely, #1 plastic deformation #4 additive manufacturing #5 surface modification. The keyword alluvial map shows that the longest-lasting research concepts in the field are mechanical property, microstructure, corrosion behavior, etc., and emerging keywords are additive manufacturing, surface modification, dynamic recrystallization, etc. The most recent research on reference clustering has six subfields. Namely, #0 microstructure, #2 sem, #3 additive manufacturing, #4 laser powder bed fusion, #5 implant, and #7 Zn-1Mg. Conclusion: The results of the bibliometric study provide the current status and trends of research on zinc-based biodegradable metallic materials, which can help researchers identify hot spots and explore new research directions in the field.

Porcine ß-Defensin 114: Creating a Dichotomous Response to Inflammation.

The immunity-related functions of defensins seem to be dependent on environmental stimuli, the cell type, and the concentration of peptides. However, the function and mechanism of porcine ß-defensin 114 (pBD114) in regulating the inflammatory response to macrophages are unclear. Therefore, the modulatory effects of porcine pBD114 on the inflammatory response were investigated by treating the mouse monocyte macrophage cell line RAW264.7 with different concentrations of pBD114 with or without lipopolysaccharide (LPS). RNA-seq analysis was performed to investigate the mechanisms underlying pBD114's regulation of inflammatory responses in macrophages. In addition, the inflammatory response-modulating effects of pBD114 were also further verified with a mouse assay. The results showed that 100 µg/mL of pBD114 significantly promoted the secretion of TNF-α and IL-10 in RAW264.7. However, the LPS-induced increase in TNFα in the RAW264.7 cell cultures was significantly decreased with 10 µg/mL of pBD114. These results suggest that pBD114 can exhibit pro-inflammatory activities under normal physiological conditions with 100 µg/mL of pBD114, and anti-inflammatory activities during an excessive inflammatory response with 10 µg/mL of pBD114. RNA-seq analysis was performed to gain further insights into the effects of pBD114 on the inflammatory response. Among the pBD114-promoting RAW264.7 pro-inflammatory responses, pBD114 significantly up-regulated 1170 genes and down-regulated 724 genes. KEGG enrichment showed that the differentially expressed genes (DEGs) were significantly enriched in the immune- and signal-transduction-related signaling pathways. Protein-Protein Interaction (PPI) and key driver analysis (KDA) analyses revealed that Bcl10 and Bcl3 were the key genes. In addition, pBD114 significantly up-regulated 12 genes and down-regulated 38 genes in the anti-inflammatory response. KEGG enrichment analysis revealed that the DEGs were mainly enriched in the "Cytokine-cytokine receptor interaction" signaling pathway, and PPI and KDA analyses showed that Stat1 and Csf2 were the key genes. The results of qRT-PCR verified those of RNA-seq. In vivo mouse tests also confirmed the pro- or anti-inflammatory activities of pBD114. Although the inflammatory response is a rapid and complex physiological reaction to noxious stimuli, this study found that pBD114 plays an essential role mainly by acting on the genes related to immunity, signal transduction, signaling molecules, and interactions. In conclusion, this study provides a certain theoretical basis for the research and application of defensins.

Recent advances of mechanosensitive genes in vascular endothelial cells for the formation and treatment of atherosclerosis.

Atherosclerotic cardiovascular disease and its complications are a high-incidence disease worldwide. Numerous studies have shown that blood flow shear has a huge impact on the function of vascular endothelial cells, and it plays an important role in gene regulation of pro-inflammatory, pro-thrombotic, pro-oxidative stress, and cell permeability. Many important endothelial cell mechanosensitive genes have been discovered, including KLK10, CCN gene family, NRP2, YAP, TAZ, HIF-1α, NF-κB, FOS, JUN, TFEB, KLF2/KLF4, NRF2, and ID1. Some of them have been intensively studied, whereas the relevant regulatory mechanism of other genes remains unclear. Focusing on these mechanosensitive genes will provide new strategies for therapeutic intervention in atherosclerotic vascular disease. Thus, this article reviews the mechanosensitive genes affecting vascular endothelial cells, including classical pathways and some newly screened genes, and summarizes the latest research progress on their roles in the pathogenesis of atherosclerosis to reveal effective therapeutic targets of drugs and provide new insights for anti-atherosclerosis.

Smartphone-Aided Fluorescence Detection of Cardiac Biomarker Myoglobin by a Ratiometric Fluorescent AuNCs-QDs Nanohybrids Probe with High Sensitivity.

Simple and sensitive detection of cardiac biomarkers is of great significance for early diagnosis and prevention of acute myocardial infarction (AMI). Here, a ratiometric fluorescent nanohybrids probe (AuNCs-QDs) was synthesized through the coupling of bovine serum albumin-functionalized gold nanoclusters (AuNCs) with CdSe/ZnS quantum dots (QDs) to realize simple and sensitive detection of cardiac biomarker myoglobin (Mb). The AuNCs-QDs probe shows pink fluorescence under UV light, with two emission peaks at 468 nm and 630 nm belonging to QDs and AuNCs, respectively. Importantly, the presence of Mb caused fluorescence quenching of the blue-emitting QDs, thereby inhibiting the fluorescence resonance energy transfer (FRET) process between QDs and AuNCs, and reducing the fluorescence intensity ratio (F468/F630) of AuNCs-QDs probe effectively. As the concentration of Mb increases, the ratiometric fluorescent probe also exhibits a visible fluorescence color change. The detection limit was as low as 4.99 µg/mL, and the response of the probe to Mb showed a good linear relationship up to 0.52 mg/mL. Moreover, the probe has excellent specificity for Mb. Besides, the AuNCs-QDs has been applied to detect Mb of urine samples. More importantly, we also developed an AuNCs-QDs probe modified smartphone-aided paper-based strip for on-site monitoring of Mb. As far as we know, this is the first report of a smartphone-aided paper-based strip for on-site quick monitoring of Mb, which provides a useful approach for AMI biomarker monitoring and may can be extended to other medical diagnostics.

Atomic force microscopy in disease-related studies: Exploring tissue and cell mechanics.

Despite significant progress in human medicine, certain diseases remain challenging to promptly diagnose and treat. Hence, the imperative lies in the development of more exhaustive criteria and tools. Tissue and cellular mechanics exhibit distinctive traits in both normal and pathological states, suggesting that "force" represents a promising and distinctive target for disease diagnosis and treatment. Atomic force microscopy (AFM) holds great promise as a prospective clinical medical device due to its capability to concurrently assess surface morphology and mechanical characteristics of biological specimens within a physiological setting. This review presents a comprehensive examination of the operational principles of AFM and diverse mechanical models, focusing on its applications in investigating tissue and cellular mechanics associated with prevalent diseases. The findings from these studies lay a solid groundwork for potential clinical implementations of AFM. RESEARCH HIGHLIGHTS: By examining the surface morphology and assessing tissue and cellular mechanics of biological specimens in a physiological setting, AFM shows promise as a clinical device to diagnose and treat challenging diseases.

Development and validation of a nomogram model for predicting the risk of venous thromboembolism in lymphoma patients undergoing chemotherapy: a prospective cohort study conducted in China.

BACKGROUND: The mechanism of Venous thromboembolism (VTE) is complicated and difficult to prevent due to factors such as bone marrow invasion, therapy, and immune-mediated effects. This study aims to establish a nomogram model for predicting the risk of thrombosis in lymphoma patients undergoing chemotherapy, which has been increasing over the past 30 years. METHODS: The data of lymphoma patients from the Affiliated Cancer Hospital of Chongqing University in China between 2018 and 2020 were analyzed. This included age, sex, body mass index, ECOG score, histological type, Ann Arbour Stage, white blood cells count, haemoglobin level, platelet count, D-dimer level, and chemotherapy cycle. Univariate and multivariate cox analysis was used to determine the risk factors for VTE. Characteristic variables were selected to construct a nomogram model which was then evaluated using ROC curve and calibration. RESULTS: Age, sex, PLT, D-dimer and chemotherapy cycle were considered as independent influencing factors of VTE. The mean (standard deviation) of the C index, AUC and Royston D statistics of 1000 cross-validations of the Nomogram model were 0.78 (0.01), 0.81 (0.01) and 1.61(0.07), respectively. It indicates a good calibration degree and applicability value as shown by the calibration curve. The DCA curve showed a rough threshold range of 0.05-0.60 with a good model. CONCLUSIONS: We have established and validated a nomogram model for predicting the risk of thrombosis in lymphoma patients. This model can assess the risk of thrombosis in each individual patient, enabling the identification of high-risk groups and targeted preventive treatment.

A Bioinspired Flexible Sensor for Electrochemical Probing of Dynamic Redox Disequilibrium in Cancer Cells.

Malignant tumors pose a serious risk to human health. Ascorbic acid (AA) has potential for tumor therapy; however, the mechanism underlying the ability of AA to selectively kill tumor cells remains unclear. AA can cause redox disequilibrium in tumor cells, resulting in the release of abundant reactive oxygen species, represented by hydrogen peroxide (H2 O2 ). Therefore, the detection of H2 O2 changes can provide insight into the selective killing mechanism of AA against tumor cells. In this work, inspired by the ion-exchange mechanism in coral formation, a flexible H2 O2 sensor (PtNFs/CoPi@CC) is constructed to monitor the dynamics of H2 O2 in the cell microenvironment, which exhibits excellent sensitivity and spatiotemporal resolution. Moreover, the findings suggest that dehydroascorbic acid (DHA), the oxidation product of AA, is highly possible the substance that actually acts on tumor cells in AA therapy. Additionally, the intracellular redox disequilibrium and H2 O2 release caused by DHA are positively correlated with the abundance and activity of glucose transporter 1 (GLUT1). In conclusion, this work has revealed the potential mechanism underlying the ability of AA to selectively kill tumor cells through the construction and use of PtNFs/CoPi@CC. The findings provide new insights into the clinical application of AA.