Engineered endothelium-mimicking antithrombotic surfaces via combination of nitric oxide-generation with fibrinolysis strategies.

Thrombosis associated with implants can severely impact therapeutic outcomes and lead to increased morbidity and mortality. Thus, developing blood-contacting materials with superior anticoagulant properties is essential to prevent and mitigate device-related thrombosis. Herein, we propose a novel single-molecule multi-functional strategy for creating blood-compatible surfaces. The synthesized azide-modified Cu-DOTA-(Lys)3 molecule, which possesses both NO release and fibrinolysis functions, was immobilized on material surfaces via click chemistry. Due to the specificity, rapidity, and completeness of click chemistry, the firmly grafted Cu-DOTA-(Lys)3 endows the modified material with excellent antithrombotic properties of vascular endothelium and thrombolytic properties of fibrinolytic system. This surface effectively prevented thrombus formation in both in vitro and in vivo experiments, owing to the synergistic effect of anticoagulation and thrombolysis. Moreover, the modified material maintained its functional efficacy after one month of PBS immersion, demonstrating excellent stability. Overall, this single-molecule multifunctional strategy may become a promising surface engineering technique for blood-contacting materials.

Novel catalytic behavior of defective nanozymes with catalase-mimicking characteristics for the degradation of tetracycline.

Although nanozymes have shown significant potential in wastewater treatment, enhancing their degradation performance remains challenging. Herein, a novel catalytic behavior was revealed for defective nanozymes with catalase-mimicking characteristics that efficiently degraded tetracycline (TC) in wastewater. Hydroxyl groups adsorbed on defect sites facilitated the in-situ formation of vacancies during catalysis, thereby replenishing active sites. Additionally, electron transfer considerably enhanced the catalytic reaction. Consequently, numerous reactive oxygen species (ROS) were generated through these processes and subsequent radical reactions. The defective nanozymes, with their unique catalytic behavior, proved effective for the catalytic degradation of TC. Experimental results demonstrate that •OH, •O2-, 1O2 and e- were the primary contributors to the degradation process. In real wastewater samples, the normalized degradation rate constant for defective nanozymes reached 26.0 min-1 g-1 L, exceeding those of other catalysts. This study reveals the new catalytic behavior of defective nanozymes and provides an effective advanced oxidation process for the degradation of organic pollutants.

Combination of multivalent DR5 receptor clustering agonists and histone deacetylase inhibitors for treatment of colon cancer.

Death Receptor 5 (DR5) targeted therapies offer significant promise due to their pivotal role in mediating the extrinsic pathway of apoptosis. Despite DR5 overexpression in various malignancies and the potential of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), clinical implementations of anti-DR5 monoclonal antibodies (mAbs) have been hampered by suboptimal outcomes potentially due to lack of receptor clustering. To address the limitation, we developed N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-based conjugates integrating multiple copies of DR5-targeting peptide (cyclic WDCLDNRIGRRQCVKL; cDR5) to enhance receptor clustering and apoptosis. Three conjugates with variable number of cDR5 were prepared and denoted as PH-cDR5 (high valence), PM-cDR5 (medium valence) and PL-cDR5 (low valence). Our studies in TRAIL-sensitive and resistant cancer cell lines demonstrated that the HPMA copolymer-peptide conjugates (P-cDR5) significantly improved DR5 receptor clustering and induced apoptosis effectively. In TRAIL-sensitive colon cancer cells (COLO205, HCT-116), P-cDR5 showed efficacy comparable to anti-DR5 mAb Drozitumab (DRO), but P-cDR5 outperformed DRO in TRAIL-resistant cells (HT-29), highlighting the importance of efficient receptor clustering. In COLO205 cells PM-cDR5 exhibited an IC50 of 94 pM, while PH-cDR5 had an even lower IC50 of 15 pM (based on cDR5 equivalent concentration), indicating enhanced potency of the multivalent HPMA copolymer-based system with a flexible polymer backbone in comparison with the IC50 for TRAIL at 0.12 nM. Combining P-cDR5 with valproic acid, a histone deacetylase inhibitor, resulted in further enhancement of apoptosis inducing efficacy, along with destabilizing mitochondrial membranes and increased sensitivity of TRAIL-resistant cells. These findings suggest that attaching multiple cDR5 peptides to a flexible water-soluble polymer carrier not only overcomes the limitations of previous designs but also offers a promising avenue for treating resistant cancers, pointing toward the need for further preclinical exploration and validation of this innovative strategy.

A modular, human body-mimicking phantom with active thermoregulation capabilities for validation and verification of convective hyperthermia devices.

OBJECTIVES: This study aims to design and fabricate a modular phantom for hyperthermia applications, addressing interpatient variability in thermal regulation mechanisms like sweating rate, metabolic heat production, and blood redistribution. MATERIALS & METHODS: The phantom can be constructed in various weights and dimensions by connecting identical units. Each unit consists of an agar-based block, an ethyl cellulose-based top layer, a heat source, deep and superficial water circulation, and a sweating mechanism. Agar and ethyl cellulose gels mimic the thermal properties of human tissues and fat respectively. The blocks are wrapped in PVC foil to prevent water evaporation. A heating wire, coiled around an embedded aluminum tubing simulates metabolic heat production. A superficial water circulation mimics skin capillaries. A water pump ensures a steady flow rate throughout the tubing system. Sweat production is simulated using a water pump and perforated tubing. A programmed controller maintains core temperature in a normal operating mode and simulates an anesthetized patient in anesthesia mode. RESULTS: Temperature uniformity and regulation were assessed under varying environmental conditions. The phantom effectively regulated its core temperature at 37.0 °C +/- 0.7 °C with an ambient temperature ranging between 21 °C and 30 °C. Activating the water circulation reduced the maximum temperature gradient within the phantom from 4.70 °C to 1.92 °C. CONCLUSION: The versatile phantom successfully models heat exchange processes. Its thermal properties, dimensions, and heat exchange rates can be tuned to mimic different patient models. These are promising results as an effective tool for hyperthermia device validation and verification, representing human physiological responses.

Unraveling the in planta population dynamics of the plant pathogen Ralstonia pseudosolanacearum by mathematical modeling.

Ralstonia pseudosolanacearum, a plant pathogen responsible for bacterial wilt in numerous plant species, exhibits paradoxical growth in the host by achieving high bacterial densities in xylem sap, an environment traditionally considered nutrient-poor. This study combined in vitro experiments and mathematical modeling to elucidate the population dynamics of R. pseudosolanacearum within plants. To simulate the xylem environment, a tomato xylem-mimicking medium was developed. Then, a mathematical model was constructed using in vitro data and employed to simulate the dynamics of bacterial density and xylem sap composition during plant infection. The model accurately reproduced in planta experimental observations, including high bacterial densities and the depletion of glutamine and asparagine. Additionally, the model estimated the minimal number of bacteria required to initiate infection, the timing of infection post-inoculation, the bacterial mortality rate within the plant and the rate at which bacterial putrescine is assimilated by the plant. The findings demonstrate that xylem sap can sustain high bacterial densities, provides an explanatory framework for the presence of acetate, putrescine and 3-hydroxybutyrate in the sap of infected xylem and give clues as to the role of putrescine in the virulence of R. pseudosolanacearum.

Fast tailoring the ZIF-8 surface microenvironment at ambient temperature to boost glucose oxidase-like activity of AuNPs for biosensing.

Rational design and tailoring of the surface microenvironment surrounding the catalytic sites, such as noble metal nanoparticles, is an effective way to enhance the catalytic activity of mimicking enzymes. However, it remains on-going challenges to regulate the microenvironment of the catalytic sites due to the lack of tunable variability in structural precision of conventional solid catalysts. Herein, three types of zeolitic imidazolate framework-8 (ZIF-8) with different major crystal facet orientations, i.e., cubic with (100) facets (denoted ZIF-8c), truncated dodecahedral with (100), (110) facets (denoted ZIF-8tr), and dodecahedral with (110) facets (denoted ZIF-8r), were developed facilely using an electrochemical method by switching the potential at ambient temperature. Because the Zn2+ nodes were predominantly exposed on the (100) facets of ZIF-8, while the ligands were mainly exposed on the (110) facets. Hence, gold nanoparticles (AuNPs) showed differential glucose oxidase (GOx)-like activities when anchored in situ on different crystal facets of ZIF-8 and obeyed the following order ZIF-8c/Au>ZIF-8tr/Au>ZIF-8r/Au. Notably, both the metal nodes and aromatic linkers of ZIF-8 interacted with AuNPs through coordination and π-π interactions. The Zn2+ nodes facilitated the formation of the electron-deficient Au species. The electron transfer from AuNPs to Zn2+ sites effectively boosted the catalytic activity. It was known that directly tailoring the microenvironment at the supporting sites of noble metal catalysts to boost catalysis through a facile electrochemical method was not reported. Based on the favorable GOx-like activity and long-term stability of ZIF-8tr/Au, a highly sensitive electrochemical biosensing platform for assaying squamous cell carcinoma antigen (SCCA) was developed. It enabled fg-level detection of cancer marker.

Augmenting Protein Degradation Capacity of PROTAC through Energy Metabolism Regulation and Targeted Drug Delivery.

The ubiquitin-proteasome system (UPS) is responsible for degrading over 70-80% of cellular proteins. Consequently, proteolysis-targeting chimeras (PROTACs) are developed to induce the ubiquitination and subsequent degradation of proteins of interest (POIs) by the UPS. To amplify the therapeutic efficacy of PROTACs, energy metabolism regulation is first harnessed to boost UPS function in tumor cells. Proteomic and ubiquitinome analyzes reveal that total ubiquitinated proteins and proteasome activity are significantly increased in 143B and MDA-MB-231 tumor cells following fasting-mimicking diet (FMD) treatment. As a result, the degradation efficiency of PROTACs targeting focal adhesion kinase (FAK-P) or bromodomain-containing protein 4 (BRD4-P) is significantly enhanced in FMD-treated 143B and MDA-MB-231 tumor cells. Then, silica-coated iron oxide nanoparticles are developed modified with tumor cell membranes for targeted delivery of PROTACs. Magnetic resonance imaging (MRI) and fluorescence imaging confirm that nanocarriers significantly improve the delivery efficiency of PROTACs in FMD-treated 143B or MDA-MB-231 tumors. In vivo studies demonstrate that the antitumor efficacy of FAK-P and BRD4-P is greatly augmented when combined with targeted delivery and FMD treatment. Overall, this study presents a strategy to enhance the efficacy of PROTACs in cancer therapy.

Ectopic Cervical Thymic Tissue Mimicking Parathyroid Hyperplasia: A Rare Occurrence Linked to Graves Disease.

Thymic hyperplasia has occasionally been reported in patients with Graves disease (GD). However, ectopic cervical thymic hyperplasia in the setting of hyperthyroid GD is exceptionally rare. We describe a case of a 54-year-old Thai woman who presented with hyperthyroidism, diplopia, and pretibial myxedema. She underwent a total thyroidectomy because of diplopia caused by Graves ophthalmopathy. During the surgery, 3 macroscopically abnormal enlargements of parathyroid gland-like tissue were identified and removed. Histopathology revealed hyperplastic thymic tissue mixed with 1 normal-sized parathyroid gland at the location of the left upper parathyroid gland, and thymic tissue was found in the sample labeled as the right upper parathyroid gland. Notably, the sample labeled as the right lower parathyroid gland was actually determined to be a lymph node. Preoperative blood samples showed normal serum calcium and parathyroid hormone levels. Postoperatively, computed tomography of the chest showed thymic hyperplasia in the anterior mediastinum, which slightly regressed at the 9-month follow-up. The patient had transient hypoparathyroidism requiring oral calcium and active vitamin D supplements for 6 months postoperatively. Ectopic cervical thymic hyperplasia can be found in GD and might be indistinguishable from parathyroid hyperplasia. Biochemical evaluations are required to exclude concomitant hyperparathyroidism, and a conservative approach should be considered.

Bacteria-Mediated Tumor-Targeting Delivery of Multienzyme-Mimicking Covalent Organic Frameworks Promoting Pyroptosis for Combinatorial Sono-Catalytic Immunotherapy.

Pyroptosis, an inflammatory cell death, has attracted great attention for potentiating a strong immune response against tumor cells. However, developing powerful pyroptosis inducers and then activating specific pyroptosis still remains challenging. Herein, a PEG-CuP-COF@∆St nanosystem is rationally designed, consisting of PEG-CuP-COF nanozyme pyroptosis inducers and tumor-targeting bacteria of the Salmonella Typhimurium strain VNP20009 (ΔSt), with an affinity for the tumor hypoxic microenvironment. The PEG-CuP-COF nanozymes possessed excellent sonodynamic performance and multienzyme-mimicking activities to generate reactive oxygen species (ROS) and then induce potent pyroptosis. The superoxide dismutase- and peroxidase-mimicking activities of PEG-CuP-COF catalytically produced hydrogen peroxide (H2O2) and hydroxyl radicals (•OH) which have important value in triggering acute inflammatory responses and pyroptosis. Moreover, PEG-CuP-COF showed outstanding glutathione peroxidase-mimicking activities, impairing the antioxidant defense in tumor cells and enhancing sonodynamic efficiency by making them more vulnerable to ROS-induced damage. During in vivo studies, PEG-CuP-COF@∆St nanosystem with its self-driven property exhibited impressive tumor-targeting capability and activated Caspase-3/gasdermin E-dependent pyroptosis to inhibit tumor growth. More importantly, it induced a powerful immune memory effect to prevent bone metastasis. In summary, this study introduces an innovative approach for combinatorial sono-catalytic immunotherapy using bacteria-mediated tumor-targeting delivery of nanozymes as specific pyroptosis inducers.

A colorimetric platform using highly active Prussian blue composite nanocubes for the rapid determination of ascorbic acid and acid phosphatase.

Cobalt-doped Prussian blue composite nanocubes (Co-PB NCs) were synthesized, which can quickly convert O2 to O2•- and 1O2. Due to the presence of cobalt and iron transition metal redox electron pairs, Co-PB NCs with high oxidase mimetic activity can rapidly oxidize the substrate 3,3',5,5'-tetramethylbenzidine (TMB) to produce blue products (ox-TMB) without the assistance of unstable H2O2. Using ascorbic acid-2-phosphate trisodium salt (AAP) as a substrate, it can be converted to reduced ascorbic acid (AA) under acid phosphatase (ACP) hydrolysis, resulting in suppression of TMB oxidation. Therefore, an enzyme cascade signal amplification strategy for rapid colorimetric detection of AA/ACP was developed based on the high-efficiency oxidase-like activity of Co-PB NCs combined with the hydrolysis effect of ACP. The color changes at low concentrations of AA and ACP could be observed by the naked eye, and the detection limits of AA and ACP were 1.67 µM and 0.0266 U/L, respectively. The developed colorimetric method was applied to the determination of AA in beverages and ACP in human serum, and the RSDs were less than 3%, showing good reproducibility. This work provides a promising strategy for the use of metal-doped Prussian blue composite material for the construction of rapid colorimetric sensing platforms that avoid the use of unstable hydrogen peroxide.

Intermittent Fasting and Fasting-mimicking Diet: Promising Strategies in Cancer Management.

In the current review, we aim to elucidate the advancements concerning the roles and fundamental mechanisms of intermittent fasting (IF) and fasting-mimicking diet (FMD) in cancers. As a dietary intervention,IF and FMD potentially impede tumor growth by modulating multiple signaling pathways, such as AKT, Nrf2, and AMPK pathways.Moreover, IF and FMD have been reported to be associated with the tumor immune response by regulating various immune cells including tumor-associated macrophages (TAMs), monocytic myeloid-derived suppressor cells (MDSCs), T cells, and B cells.Additionally, IF and FMD can enhance the efficacy and tolerability of therapy, concurrently reducing therapy-induced side effects. Furthermore, several clinical trials have underscored the safety, feasibility, and positive impact on the quality of life associated with IF and FMD, thereby augmenting the effectiveness of conventional anti-- tumor therapies while ameliorating treatment-related side effects. This review provides a comprehensive synthesis of findings and elucidates the underlying mechanisms of IF and FMD in cancer progression and therapy.

Three in one: A multifunctional oxidase-mimicking Ag/Mn3O4 nanozyme for colorimetric determination, precise identification, and broad-spectrum inactivation of foodborne pathogenic bacteria.

A multifunctional oxidase-mimicking Ag/Mn3O4 was prepared, catalyzing the 3, 3', 5, 5'-tetramethylbenzidine (TMB) chromogenic reaction. Six foodborne pathogenic bacteria species, including Escherichia coli, Staphylococcus aureus, Salmonella enterica, Listeria monocytogenes, Bacillus cereus, and Cronobacter sakazakii, were observed to differentially inhibit its oxidase-like activity, resulting in decelerating the TMB chromogenic reaction. Owing to these properties, the following achievements were achieved: colorimetric determination of these bacteria with high sensitivity can be achieved using Ag/Mn3O4 + TMB reaction system; precise identification of these bacteria at different concentrations, including individual bacterium, binary mixtures, and even multivariate mixtures, can be effectively realized by combining the Ag/Mn3O4-based colorimetric sensor array with principal component analysis (PCA); broad-spectrum inactivation of these bacteria can be remarkably realized through catalyzation of Ag/Mn3O4 to generate superoxide anion free radicals. Therefore, our proposed Ag/Mn3O4 holds significant application potential in the colorimetric determination, precise identification, and broad-spectrum inactivation of foodborne pathogenic bacteria.

Novel lateral flow assay to detect H2O2 by utilizing self-biotinylation of G-quadruplex.

We herein describe a novel lateral flow assay (LFA) to detect H2O2 by utilizing self-biotinylation of G-quadruplex (G4). In this strategy, the G4 strand promotes the self-biotinylation of G4 itself in the presence of H2O2, which is then allowed to bind to the FAM-labeled complementary detector probe. The resulting biotin-labeled G4/FAM-detector probe complex is captured on the test line, producing a red-colored band during lateral flow readout. Based on this unique approach, we achieved the naked-eye detection of target H2O2 at concentrations as low as 1 µM, with reliable quantification down to 0.388 µM. This method also demonstrated exceptional specificity in distinguishing H2O2 from other non-target molecules. We further verified its versatile applicability by reliably identifying another biomolecule, choline, by coupling with choline oxidase, which generates H2O2 during oxidation. This novel LFA strategy holds great promise as a powerful point-of-care testing (POCT) platform for detecting a large spectrum of target biomolecules by employing their corresponding oxidases.

3D Printing Materials Mimicking Human Tissues after Uptake of Iodinated Contrast Agents for Anthropomorphic Radiology Phantoms.

(1) Background: 3D printable materials with accurately defined iodine content enable the development and production of radiological phantoms that simulate human tissues, including lesions after contrast administration in medical imaging with X-rays. These phantoms provide accurate, stable and reproducible models with defined iodine concentrations, and 3D printing allows maximum flexibility and minimal development and production time, allowing the simulation of anatomically correct anthropomorphic replication of lesions and the production of calibration and QA standards in a typical medical research facility. (2) Methods: Standard printing resins were doped with an iodine contrast agent and printed using a consumer 3D printer, both (resins and printer) available from major online marketplaces, to produce printed specimens with iodine contents ranging from 0 to 3.0% by weight, equivalent to 0 to 3.85% elemental iodine per volume, covering the typical levels found in patients. The printed samples were scanned in a micro-CT scanner to measure the properties of the materials in the range of the iodine concentrations used. (3) Results: Both mass density and attenuation show a linear dependence on iodine concentration (R2 = 1.00), allowing highly accurate, stable, and predictable results. (4) Conclusions: Standard 3D printing resins can be doped with liquids, avoiding the problem of sedimentation, resulting in perfectly homogeneous prints with accurate dopant content. Iodine contrast agents are perfectly suited to dope resins with appropriate iodine concentrations to radiologically mimic tissues after iodine uptake. In combination with computer-aided design, this can be used to produce printed objects with precisely defined iodine concentrations in the range of up to a few percent of elemental iodine, with high precision and anthropomorphic shapes. Applications include radiographic phantoms for detectability studies and calibration standards in projective X-ray imaging modalities, such as contrast-enhanced dual energy mammography (abbreviated CEDEM, CEDM, TICEM, or CESM depending on the equipment manufacturer), and 3-dimensional modalities like CT, including spectral and dual energy CT (DECT), and breast tomosynthesis.

[Analysis of RhC Antigen Weak Expression Combined with Mimicking Autoanti-Ce and Homologous Anti-Jkb Causing Mismatch].

OBJECTIVE: To investigate the reasons for the weak expression of RHCE gene in a patient whose mimicking anti-Ce combined with anti-Jkb caused cross-matching non-combination. METHODS: ABO, Rh, and Kidd blood group antigens were identified by test tube method and capillary centrifugation. Antibody screening and antibody specificity identification were performed using saline, polybrene and antiglobulin in tri-media association with multispectral cells. RHCE gene sequencing and haploid analysis were performed by multiplex PCR technique and RHCE protein modeling was performed using Swiss-Model. RESULTS: The serum of the patient contained anti-Ce mimicking autoantibodies along with anti-Jkb antibodies. c.48G>C, c.150C>T, c.178C>A, c.201A>G, c.203A>G, and c.307C>T mutations were detected in the RHCE triple-molecule sequencing. A 109 bp insertion sequence was found in intron 2, with fragment loss from intron 5-8. The Rh-group genotype was DCe/DCe , and phenotype was CCDee. CONCLUSION: Genotyping techniques can assist in deducing the molecular mechanisms of some weakly expressed RhC, c, E, and e in patients' sera to aid in the identification of difficult antibodies and thus ensure the safety of patients' blood transfusion.

Exploring the Impact of Fasting and Fasting-Mimicking Diets on Type 2 Diabetes Management in Adults: A Systematic Review.

Type 2 diabetes poses significant global health challenges, affecting both the quality of life and healthcare systems. This systematic review evaluates the efficacy of fasting and fasting-mimicking diets (FMD) in managing type 2 diabetes, with a focus on their effects on glycemic control, lipid profiles, and overall metabolic health in adult patients. A comprehensive search of PubMed and Cochrane Library databases identified several studies utilizing various fasting protocols, including intermittent fasting and FMD. Data synthesis and bias assessment were conducted using established methodologies, including the Cochrane Risk of Bias 2 (RoB 2) tool. The review found that fasting interventions significantly improve glycemic control and reduce body weight, with some protocols notably lowering HbA1c levels (p<0.05), highlighting the strong potential of fasting in diabetes management. However, the results varied, suggesting that individual differences in metabolic responses and adherence levels influence outcomes. In conclusion, while fasting and FMD show promise for improving metabolic health and managing diabetes, more standardized research is needed to understand the underlying mechanisms, optimize protocols, and confirm long-term benefits. Future research should prioritize larger sample sizes and extended follow-up periods to inform comprehensive clinical practice guidelines.

VP-net: an end-to-end deep learning network for elastic wave velocity prediction in human skin in vivo using optical coherence elastography.

Introduction: Acne vulgaris, one of the most common skin conditions, affects up to 85% of late adolescents, currently no universally accepted assessment system. The biomechanical properties of skin provide valuable information for the assessment and management of skin conditions. Wave-based optical coherence elastography (OCE) quantitatively assesses these properties of tissues by analyzing induced elastic wave velocities. However, velocity estimation methods require significant expertise and lengthy image processing times, limiting the clinical translation of OCE technology. Recent advances in machine learning offer promising solutions to simplify velocity estimation process. Methods: In this study, we proposed a novel end-to-end deep-learning model, named velocity prediction network (VP-Net), aiming to accurately predict elastic wave velocity from raw OCE data of in vivo healthy and abnormal human skin. A total of 16,424 raw phase slices from 1% to 5% agar-based tissue-mimicking phantoms, 28,270 slices from in vivo human skin sites including the palm, forearm, back of the hand from 16 participants, and 580 slices of facial closed comedones were acquired to train, validate, and test VP-Net. Results: VP-Net demonstrated highly accurate velocity prediction performance compared to other deep-learning-based methods, as evidenced by small evaluation metrics. Furthermore, VP-Net exhibited low model complexity and parameter requirements, enabling end-to-end velocity prediction from a single raw phase slice in 1.32 ms, enhancing processing speed by a factor of ∼100 compared to a conventional wave velocity estimation method. Additionally, we employed gradient-weighted class activation maps to showcase VP-Net's proficiency in discerning wave propagation patterns from raw phase slices. VP-Net predicted wave velocities that were consistent with the ground truth velocities in agar phantom, two age groups (20s and 30s) of multiple human skin sites and closed comedones datasets. Discussion: This study indicates that VP-Net could rapidly and accurately predict elastic wave velocities related to biomechanical properties of in vivo healthy and abnormal skin, offering potential clinical applications in characterizing skin aging, as well as assessing and managing the treatment of acne vulgaris.

Narrative review of tissue-mimicking materials for MRI phantoms: Composition, fabrication, and relaxation properties.

INTRODUCTION: Tissue-mimicking materials (TMMs) are now essential reference objects for quality control, development and training in all medical imaging modalities. This review aims to provide a comprehensive synthesis of materials used in the fabrication of TMMs for MRI phantoms, focusing on their composition, fabrication methods, and relaxation properties (T1 and T2). METHODS: A systematic review was conducted, covering articles published between 1980 and 2023. Inclusion criteria encompassed studies involving physical MRI phantoms with measured T1 and T2 relaxation times. Exclusion criteria filtered out non-MRI studies, and digital/computational models. RESULTS: The review identifies and categorizes TMMs based on their primary gelling agents: agar, carrageenan, gelatin, polyvinyl alcohol (PVA), and other less common gels. Agar emerged as the most frequently used gelling agent due to its versatility and favorable MRI signal properties. Carrageenans, noted for their strength and minimal impact on T2 values, are often used in combination with agar. Gelatin, PVA, and other materials like Polyvinyl chloride (PVC) and PolyvinylPyrrolidone (PVP) also demonstrate unique advantages for specific applications. The review also highlights the challenges in phantom stability and the impact of various additives on the relaxation properties. CONCLUSION: This synthesis provides a valuable guide for the fabrication of MRI phantoms tailored to desired T1 and T2 relaxation times, facilitating the development of more accurate and reliable imaging tools. Understanding the detailed properties of TMMs is fundamental to improve the quality control and educational applications of MRI technologies, especially with the advent of new magnetic field strengths and parametric imaging techniques. IMPLICATION FOR PRACTICE: As experts in MRI systems, radiographers, educators, and researchers need to understand TMM compositions and methods of fabrications to develop MRI phantoms for educational tools and research purposes. This review serves as a valuable resource to guide them in these efforts.

The Functional Dilemma of Nectar Mimic Staminodes in Parnassia wightiana (Celastraceae): Attracting Pollinators and Florivorous Beetles.

While floral signaling plays a central role in the reproductive success of all animal-pollinated plants, it may also attract herbivores eager to feed on flowers. False nectaries with glossy surfaces reflecting incident light may produce signals that attract floral visitors guiding their movements to and within the flower. Whether false nectaries also attract herbivores that lower the reproductive success of natural populations requires attention. In this study, we focus on Parnassia wightiana, a subalpine species with a whorl of staminodes that act as false nectaries attracting bees, flies, and herbivorous beetles. We tested the functions of staminodes using controlled manipulative experiments under field and lab conditions. We found a significant decrease in pollinator visits, and subsequent seed set, in flowers in which we removed staminodes or staminode apices confirming the function of these organs. In our natural populations, we found that a beetle, Nonarthra variabilis (Alticinae; Chrysomelidae), chews first on staminode apices, then it eats the entire staminodes and other flower parts, but rarely feeds on ovaries. Additional experiments suggested these beetles preferred staminodes to ovaries. Our results suggest this is a case of selective florivory, in which staminodes play a dual role, attracting pollinators and herbivores at the same time causing the attractive dilemma. Although selective florivory by beetles did not directly damage fruits, it influenced plant-pollinator interactions, decreasing reproductive success in plant populations. Our study highlights the importance of plant-pollinator-herbivore interactions in selecting floral traits.

Hypoxia-Mimicking Mediated Macrophage-Elimination of Erythrocytes Promotes Bone Regeneration via Regulating Integrin αvß3/Fe2+-Glycolysis-Inflammation.

Erythrocytes are the dominant component of a blood clot in terms of volume and number. However, longstanding compacted erythrocytes in blood clots form a physical barrier and make fibrin mesh more anti-fibrinolytic, thus impeding infiltration of mesenchymal stem cells. The necrosis or lysis of erythrocytes that are not removed timely can also lead to the release of pro-inflammatory toxic metabolites, interfering with bone regeneration. Proper bio-elimination of erythrocytes is essential for an undisturbed bone regeneration process. Here, hypoxia-mimicking is applied to enhance macrophage-elimination of erythrocytes. The effect of macrophage-elimination of erythrocytes on the macrophage intracellular reaction, bone regenerative microenvironment, and bone regeneration outcome is investigated. Results show that the hypoxia-mimicking agent dimethyloxalylglycine successfully enhances erythrophagocytosis by macrophages in a dose-dependent manner primarily by up-regulating the expression of integrin αvß3. Increased phagocytosed erythrocytes then regulate macrophage intracellular Fe2+-glycolysis-inflammation, creating an improved bone regenerative microenvironment characterized by loose fibrin meshes with down-regulated local inflammatory responses in vivo, thus effectively promoting early osteogenesis and ultimate bone generation. Modulating macrophage-elimination of erythrocytes can be a promising strategy for eradicating erythrocyte-caused bone regeneration hindrance and offers a new direction for advanced biomaterial development focusing on the bio-elimination of erythrocytes.