Structural Changes Research Articles

Real-Time Automated Geosteering Interpretation Combining Log Interpretation and 3D Horizon Tracking

Existing methods for estimating formation boundaries from well-log data only analyze the formation along the wellbore, failing to capture changes in the 3D formation structure around it. This paper presents a method for real-time 3D formation boundary interpretation using readily available well logs and seismic image data. In the proposed workflow, the mean formation boundary is estimated as a curve following the well path. 3D surfaces are then fitted through this boundary curve, aligning with the slopes and features in the seismic image data. The proposed method is tested on both synthetic and field datasets and illustrates the capabilities of accurate boundary estimation near the well path and precise representation of boundary shape changes further away from the well trajectory. With this fully automated geological interpretation workflow, human bias and interpretation uncertainty can be minimized. Subsurface conditions can be continually updated while drilling to optimize drilling decisions and further automate the geosteering process.

The structural change and determinants of global carbon footprint network embodied in international migration: A social network analysis

The carbon footprint embodied in international population mobility has a complex spatial correlation, which exacerbates the difficulty of global climate governance. However, the features, changing trends, and determinants of the carbon footprint flow embodied in global population migration are poorly understood. This study employed social network analysis and the exponential random graph model (ERGM) to investigate the structural changes and drivers of the carbon footprint network embodied in global migration from 1995 to 2015. The results showed that approximately 50% of carbon footprint flow embodied in international migration flowed from developing to developed countries. The spatial connections between countries in the network were becoming increasingly close, displaying a typical small-world structure, and showing low reciprocity and negative assortativity. Moreover, centrality analysis highlighted the United States and the European Union as being at the core of the network, whereas some emerging economies (e.g., China, India, and South Africa) were shown as having an increasing influence on the network. The determinants of network formation were divided into three effects. For node attribute effect, countries with developed economy, high proportion of industrial value added, urbanization and openness were becoming the destinations of carbon inflows from immigrants, while countries with high consumption of renewable energy and energy intensity had a trend of carbon outflows with emigrants over periods. As for exogenous network effect, the significance of economic integration on the formation of the network was strengthening, while that of geographical proximity and cultural similarity was declining. Additionally, the positive impact of self-organizational effect on the network was decreasing. This study provided guidance for countries to formulate policies to reduce the carbon emissions embodied in international migration.

Optical coherence tomography angiography for the assessment of retinal microvasculature characteristics in preterm-born children: A systematic review and meta-analysis.

This study aimed to evaluate the usefulness of optical coherence tomography angiography (OCTA) in assessing retinal microvascular structural changes in preterm-born children and compare them with those in term-born children. The Web of Science Library, Cochrane Library, PubMed, Embase, CNKI, Wanfang, VIP, and Sino Med databases were searched systematically to extract studies published till April 25, 2023. Two independent reviewers searched all the literature and completed the data extraction and quality assessment. Mean differences (MDs) with 95% confidence intervals (CIs) were used to assess the continuous estimates. STATA software (v15.1; StataCorp, College Station, TX) was used to analyze the data. Twelve published studies were eligible for inclusion in this study. The meta-analysis revealed that the foveal avascular zone (FAZ) area of preterm-born children was remarkably smaller than that of term-born children, with the laser photocoagulation (LP)-ROP group showing the most pronounced reduction. The foveal superficial capillary plexus vessel density (SCP-VD) and deep capillary plexus vessel density (DCP-VD) were remarkably higher in the preterm-born group than in the control group, with variations in subgroups (LP-ROP, anti-VEGF-ROP, SR-ROP, and Pre-T-ROP). The parafoveal SCP-VD was remarkably lower in preterm-born children compared to that of the controls, while no significant difference was identified in the parafoveal DCP-VD. Preterm-born children had a smaller FAZ area, higher foveal SCP-VD and DCP-VD, and lower parafoveal SCP-VD compared to their term-born counterparts. The parafoveal DCP-VD did not differ substantially between preterm- and term-born children. OCTA is an effective modality for assessing alterations in the retinal microvasculature in preterm children.

High-fidelity, hyper-accurate, and evolved mutants rewire atomic-level communication in CRISPR-Cas9.

The high-fidelity (HF1), hyper-accurate (Hypa), and evolved (Evo) variants of the CRISPR-associated protein 9 (Cas9) endonuclease are critical tools to mitigate off-target effects in the application of CRISPR-Cas9 technology. The mechanisms by which mutations in recognition subdomain 3 (Rec3) mediate specificity in these variants are poorly understood. Here, solution nuclear magnetic resonance and molecular dynamics simulations establish the structural and dynamic effects of high-specificity mutations in Rec3, and how they propagate the allosteric signal of Cas9. We reveal conserved structural changes and dynamic differences at regions of Rec3 that interface with the RNA:DNA hybrid, transducing chemical signals from Rec3 to the catalytic His-Asn-His (HNH) domain. The variants remodel the communication sourcing from the Rec3 α helix 37, previously shown to sense target DNA complementarity, either directly or allosterically. This mechanism increases communication between the DNA mismatch recognition helix and the HNH active site, shedding light on the structure and dynamics underlying Cas9 specificity and providing insight for future engineering principles.

Structural effects of water clusters on viscosity at high shear rates.

In this study, we use molecular dynamics simulations of liquid water to investigate how shear thinning affects the viscosity of liquid water by structural changes of the hydrogen bond network. The effect of shear on viscosity can be divided into two parts: shear-induced destruction of the hydrogen bond network and the influence of the water structure on shear viscosity. First, strong shear destroys tetrahedral structures and thus reduces the connectivity of the hydrogen bond network. It is mainly because shear deformation, characterized by compression and expansion axes, respectively, triggers the destruction and formation of hydrogen bonds, resulting in anisotropic effects on water structures. At the same time, shear destroys large clusters and enhances the formation of small ones, resulting in a decrease in average cluster sizes. Second, the change of viscosity obeys a power law relationship with the change of hydrogen bond structures, highlighting a one-to-one correspondence between structure and property. Meanwhile, in order to explain why the structure affects viscosity, we define hydrogen-bond viscosity and find that the cooperative motion of the water structures can promote momentum transfer in the form of aggregations. Hydrogen-bond viscosity accounts for 5%-50% of the total viscosity. Our results elucidate that water structures are the important structural units to explain the change of water properties.

Probe Substrate Dependencies in CYP3A4 Allosteric Inhibition: A Novel Molecular Mechanism Involving F-F' Loop Perturbations.

The biochemical basis for substrate dependences in apparent inhibition constant values (Ki) remains unknown. Our study aims to elucidate plausible structural determinants underpinning these observations. In vitro steady-state inhibition assays conducted using human recombinant CYP3A4 enzyme and testosterone substrate revealed that fibroblast growth factor receptor (FGFR) inhibitors erdafitinib and pemigatinib noncompetitively inhibited CYP3A4 with apparent Ki values of 10.2 ± 1.1 and 3.3 ± 0.9 μM, respectively. However, when rivaroxaban was adopted as the probe substrate, there were 2.0- and 3.2-fold decreases in its apparent Ki values. To glean mechanistic insights into this phenomenon, erdafitinib and pemigatinib were docked to allosteric sites in CYP3A4. Subsequently, molecular dynamics (MD) simulations of apo- and holo-CYP3A4 were conducted to investigate the structural changes induced. Comparative structural analyses of representative MD frames extracted by hierarchical clustering revealed that the allosteric inhibition of CYP3A4 by erdafitinib and pemigatinib did not substantially modulate its active site characteristics. In contrast, we discovered that allosteric binding of the FGFR inhibitors reduces the structural flexibility of the F-F' loop region, an important gating mechanism to regulate access of the substrate to the catalytic heme. We surmised that the increased rigidity of the F-F' loop engenders a more constrained entrance to the CYP3A4 active site, which in turn impedes access to the larger rivaroxaban molecule to a greater extent than testosterone and culminates in more potent inhibition of its CYP3A4-mediated metabolism. Our findings suggest a potential mechanism to rationalize probe substrate dependencies in Ki arising from the allosteric noncompetitive inhibition of CYP3A4.

Chitin‐Based Functional Films for the Colorimetric Detection of Ethylene Glycol

A new method is developed for producing large‐area color thin films for the colorimetric detection of ethylene glycol. This method is based on thermal evaporation of chitin. This process enables easy manipulation of the thickness and color patterns of the film by using shadow masks and repeated evaporation. This film is used to demonstrate a colorimetric sensor for the detection of ethylene glycol gas. The use of chitin allows the manufacture of inexpensive and environment‐friendly gas detectors. When the film is exposed to target gas, the film reacts with ethylene glycol and hydroxyl group on the chitin‐film by etherification. Then the films undergo both chemical and structural changes, resulting in color changes at low ppm concentrations. It is able to compare the sensor reaction to gases with and without the hydroxyl group. The selectivity of the sensor is confirmed by analyzing the gas containing the hydroxyl group through the linear discriminant analysis (LDA) method. It is expected that the results will be utilized to provide low‐cost and low‐power systems for gas monitoring.

Transforming Integrated Care Through Co-production: A Systematic Review Using Meta-ethnography.

There is a requirement for health and care systems and services to work on an equitable basis with people who use and provide integrated care. In response, co-production has become essential in the design and transformation of services. Globally, an array of approaches have been implemented to achieve this. This unique review explores multi-context and multi-method examples of co-production in integrated care using an exceptional combination of methods. To review and synthesise evidence that examines how co-production with service users, unpaid carers and members of staff can affect the design and transformation of integrated care services. Systematic review using meta-ethnography with input from a patient and public involvement (PPI) co-production advisory group. Meta-ethnography can generate theories by interpreting patterns between studies set in different contexts. Nine academic and four grey literature databases were searched for publications between 2012-2022. Data were extracted, analysed, translated and interpreted using the seven phases of meta-ethnography and PPI. A total of 2,097 studies were identified. 10 met the inclusion criteria. Studies demonstrated a variety of integrated care provisions for diverse populations. Co-production was most successful through person-centred design, innovative planning, and collaboration. Key impacts on service transformation were structural changes, accessibility, and acceptability of service delivery. The methods applied organically drew out new interpretations, namely a novel cyclic framework for application within integrated care. Effective co-production requires a process with a well-defined focus. Implementing co-delivery, with peer support, facilitates service user involvement to be embedded at a higher level on the 'ladder of co-production'. An additional step on the ladder is proposed; a cyclic co-delivery framework. This innovative and operational development has potential to enable better-sustained person-centred integrated care services.

Three-Dimensional Characterization of Dry Particle Coating Structures Originating from the Mechano-fusion Process.

Dry particle coating processes are of key importance for creating functionalized materials. By a change in surface structure, initiated during coating, a surface property change and thus functionalization can be achieved. This study introduces an innovative approach employing 3D X-ray micro-computed tomography (micro-CT) to characterize coated particles, consisting of spherical alumina particles (d50 = 45.64 μm), called hosts, surrounded by spherical polystyrene particles (d50 = 3.5 μm), called guests. The formed structures, hetero-aggregates, are generated by dry particle coating using mechano-fusion (MF). A deeper understanding of the influence of MF process parameters on the coating structures is a crucial step toward tailoring of coating structure, resulting surface property and functionalization. Therefore, the influence of rotational speed, process time, and total mechanical energy input during MF is explored. Leveraging micro-CT data, acquired of coated particles, enables non-stereologically biased and quantitative coating structure analysis. The guest's coating thickness is analyzed using the maximum inscribed sphere and ray method, two different local thickness measurement approaches. Particle-discrete information of the coating structure are available after a proper image processing workflow is implemented. Coating efficiency and guest's neighboring relations (nearest neighbor distance and number of neighbors inside search radius) are evaluated.

Successful Treatment of Recurrent Clostridioides difficile Infection Using a Novel, Drinkable, Oral Formulation of Fecal Microbiota.

Fecal microbiota transplants can be administered orally in encapsulated form or require invasive procedures to administer liquid formulations. There is a need for an oral liquid formulation of fecal microbiota for patients who are unable to swallow capsules, especially if they require multiple, repeated administrations. These studies were conducted to develop a protocol to manufacturean organoleptically acceptable powdered fecal microbiota formulation that can be suspended in a liquid carrier and used for fecal microbiota transplantation. Several processing steps were investigated, including extra washes of microbiota prior to lyophilization and an addition of a flavoring agent. The viability of bacteria in the transplant formulation was tested using live/dead microscopy staining and engraftment into antibiotic-treated mice. After development of a clinical protocol for suspension of the powdered microbiota, the new formulation was tested in three elderly patients with recurrent Clostridioides difficile infections and who have difficulties in swallowing capsules. Changes in the microbial community structure in one of the patients were characterized using 16S rRNA gene profiling and engraftment analysis. The processing steps used to produce an organoleptically acceptable suspension of powdered fecal microbiota did not result in loss of its viability. The powder could be easily suspended in a liquid carrier. The use of the new formulation was associated with abrogation of the cycle of C. difficile infection recurrences in the three patients. We developed a novel organoleptically acceptable liquid formulation of fecal microbiota that is suitable for use inclinical trials for patients with difficulties in swallowing capsules.

Apoptotic Vesicles Modulate Endothelial Metabolism and Ameliorate Ischemic Retinopathy via PD1/PDL1 Axis.

Pathological angiogenesis with subsequent disturbed microvascular remodeling is a major cause of irreversible blindness in a number of ischemic retinal diseases. The current anti-vascular endothelial growth factor therapy can effectively inhibit angiogenesis, but it also brings significant side effects. The emergence of stem cell derived extracellular vesicles provides a new underlining strategy for ischemic retinopathy. Apoptotic vesicles (apoVs) are extracted from stem cells from human exfoliated deciduous teeth (SHED). SHED-apoVs are delivered into the eyeballs of oxygen-induced retinopathy (a most common model of angiogenic retinal dieseases) mice through intravitreal injection. The retinal neovascularization and nonperfusion area, vascular structure, and density changes are observed during the neovascularization phase (P17) and vascular remodeling phase (P21), and visual function is measured. The expression of extracellular acidification rate and lactic acid testing are used to detect endothelial cells (ECs) glycolytic activity. Furthermore, lentivirus and neutralizing antibody are used to block PD1-PDL1 axis, investigating the effects of SHED-apoVs on glycolysis and angiogenic activities. This work shows that SHED-apoVs are taken up by ECs and modulate the ECs glycolysis, leading to the decrease of abnormal neovessels and vascular remodeling. Furthermore, it is found that, at the molecular level, apoVs-carried PD1 interacts with PDL1 on hypoxic ECs to regulate the angiogenic activation. SHED-apoVs inhibit pathological angiogenesis and promote vascular remodeling in ischemic retinopathy partially by modulating ECs glycolysis through PD1/PDL1 axis. This study provides a new potential strategy for the clinical treatment of pathological retinal neovascularization.

Optical and soft X-ray light-curve analysis during the 2022 eruption of U Scorpii: Structural changes in the accretion disk

Abstract We present our optical photometric observations of the 2022 eruption of the recurrent nova U Scorpii (U Sco) using 49152 data points over 70 d following the optical peak. We have also analyzed its soft X-ray (0.3–1 keV) light curve by the Neil Gehrels Swift Observatory. During the 2022 eruption, the optical plateau stage started 13.8–15.0 d and ended 23.8–25.0 d after the optical peak. The soft X-ray stage started 14.6–15.3 d and ended 38.7–39.5 d after the optical peak. Both stages started later and had shorter durations, and the soft X-ray light curve peaked earlier and was less luminous compared to those during the U Sco 2010 eruption. These points suggest that there were differences in the envelope mass between the different cycles of the nova eruption. Furthermore, we have analyzed the optical eclipses during the 2022 eruption. The primary eclipse was first observed 10.4–11.6 d after the optical peak, earlier than the beginning of the optical plateau stage. This sequence of events can be explained by the receding ejecta photosphere associated with the expanding nova ejecta. We have determined the ingress and egress phases of the primary eclipses and estimated the outer radius of the optical light source centered at the white dwarf (WD). During the optical plateau stage, the source radius remained ∼1.2 times larger than the Roche volume radius of the primary WD, being close to the L1 point. When the optical plateau stage ended, the source radius drastically shrank to the tidal truncation radius within a few orbital periods. This previously unresolved phenomenon can be interpreted as a structural change in U Sco where the temporarily expanded accretion disk due to the nova wind returned to a steady state.

Seasonal Variations in The Toughness of Leaves: A Case Study Using Griselinia Littoralis.

Potential effects of climate change include greater extremes of temperature and increased severity of storms. Many plants have evolved to resist the challenges of winter (freezing, dehydration, wind) in a process known as cold hardening. Sensing reducing temperatures, they make structural changes at the cellular level to increase their mechanical resistance and prevent damage. Previous work on this topic, though extensive, has been conducted under laboratory conditions rather than in the field and, whilst many workers have observed changes to cell wall thickness and composition, which imply increased mechanical strength, few have actually measured strength or any other parameter describing structural integrity. This paper describes experiments on a model system designed to measure the structural integrity of leaf laminae from plants growing naturally in the field over extended periods, allowing seasonal variations to be captured. Standard engineering properties-tensile strength and fracture toughness-were measured for leaves of Griselinia littoralis on nineteen separate occasions over a twelve-month period. Toughness (rather than strength) was found to be the controlling mechanical property. Toughness values were found to change significantly during the year, by more than a factor of two. Toughness correlated strongly with average daily soil temperature, but with a lag of about 1-2 weeks, suggesting that this is the time needed for structural adjustments to take place. Highest toughness values occurred in winter, confirming cold hardening. Increasing temperature in the spring was associated with decreasing toughness but in the summer when highest temperatures occurred, toughness increased again. This apparent "hot hardening" may be a response to dehydration. Results imply that a given leaf is able to both increase and decrease its toughness in response to temperature changes, demonstrating excellent plasticity of response. This case study of a single species establishes a method of reliably measuring changes in a plant's structural integrity due to cold hardening and other seasonal variations, which may be used to investigate the effects of climate change and other variables.

Microstructure of dendrimers functionalized with folic acid as studied by molecular dynamics simulations

Poly(amidoamine) dendrimers (PAMAM), due to their unique properties such as nanometric size and shape, monodispersity, and numerous modifiable surface groups, are promising nanocarriers in a wide range of biomedical applications. However, amine-terminated PAMAM dendrimers have been proven to be toxic at physiological pH, which limits their biomedical application. It has been approved that the binding of folic acid (FA) to dendrimer reduces nanocarrier toxicity. Also, it can selectively target cancer cells with folate receptors (FR-α) overexpression. In this study, we have explored the structural features of FA-functionalized PAMAM dendrimers using all-atom molecular dynamics (MD) simulations. To this end, third and fourth generations of PAMAM dendrimers were functionalized with FA, and MD simulations were performed for 100 ns at 310 K and 1 bar at neutral pH. We have examined the effect of FA functionalization on the molecular size, solvent accessible surface area, structural changes of amidoamine monomers, and the solvation of investigated dendrimers. Our results reveal that G4FA is the most suitable drug delivery system for cancer therapy among others.

Advanced Characterization Methodology to Unravel the Biodegradability of Metal-Organic Framework Nanoparticles in Extremely Diluted Conditions.

Porous iron(III) carboxylate metal-organic frameworks (MIL-100; MIL stands for Material of Institute Lavoisier) of submicronic size (nanoMOFs) have attracted a growing interest in the field of drug delivery due to their high drug payloads, excellent entrapment efficiencies, biodegradable character, and poor toxicity. However, only a few studies have dealt with the nanoMOF degradation mechanism, which is key to their biological applications. Complementary methods have been used here to investigate the degradation mechanism of Fe-based nanoMOFs under neutral or acidic conditions and in the presence of albumin. High-resolution STEM-HAADF coupled with energy-dispersive X-ray spectroscopy enabled the monitoring of the crystalline organization and elemental distribution during degradation. NanoMOFs were also deposited onto silicon substrates by dip-coating, forming stable thin films of high optical quality. The mean film thickness and structural changes were further monitored by IR ellipsometry, approaching the "sink conditions" occurring in vivo. This approach is essential for the successful design of biocompatible nano-vectors under extreme diluted conditions. It was revealed that while the presence of a protein coating layer did not impede the degradation process, the pH of the medium in contact with the nanoMOFs played a major role. The degradation of nanoMOFs occurred to a larger extent under neutral conditions, rapidly and homogeneously within the crystalline matrices, and was associated with the departure of their constitutive organic ligand. Remarkably, the nanoMOFs' particles maintained their global morphology during degradation.

A 6-week randomized-controlled field study: effect of isokinetic eccentric resistance training on strength, flexibility and muscle structure of the shoulder external rotators in male junior handball players.

Background: Team handball involves a tremendous amount of shoulder motion with high forces during repeated extended external range of motion. This causes shoulder complaints and overuse injuries. While eccentric training for the lower extremity shows preventive effects by improving strength, range of motion and fascicle length, there is a research gap for the shoulder joint and for advanced tissue characterization using diffusion tensor imaging. Objectives: To investigate the effects of 6-week eccentric isokinetic resistance training on strength, flexibility, and fiber architecture characteristics of the external rotators compared to an active control group in junior male handball players. Methods: 15 subjects were randomly assigned to the eccentric training group and 14 subjects to the active control group (conventional preventive training). Primary outcome measures were eccentric and concentric isokinetic strength of the external rotators, range of motion, and muscle fascicle length and fascicle volume. Results: The intervention group, showed significant changes in eccentric strength (+15%). The supraspinatus and infraspinatus muscles showed significant increases in fascicle length (+13% and +8%), and in fractional anisotropy (+9% and +6%), which were significantly different from the control group. Conclusion: Eccentric isokinetic training has a significant effect on the function and macroscopic structure of the shoulder external rotators in male junior handball players. While strength parameters and muscle structure improved, range of motion did not change. This research helps understanding the physiology of muscle and the role of eccentric training on shoulder function and muscle structure. Furthermore, DTI was found to be a promising tool for advanced tissue characterization, and the in vivo derived data can also serve as model input variables and as a possibility to extend existing ex-vivo muscle models. Future research is needed for functional and structural changes following convenient eccentric field exercises.

Neurodegeneration within the rostral spinal cord is associated with brain gray matter volume atrophy in the early stage of cervical spondylotic myelopathy.

Case-control study. Investigating the association between neurodegeneration within rostral spinal cord and brain gray matter volume (GMV) and assessing the relationship between remote neurodegenerative changes and clinical outcomes at the early phase of Cervical Spondylotic Myelopathy (CSM). University/hospital. Using Spinal Cord Toolbox, spinal cord morphometrics (cross-sectional area [CSA], gray matter area [GMA], white matter area [WMA]) of 40 patients with CSM and 28 healthy controls (HCs) were computed and compared using two-sample t test. Brain GMV of the two groups was analyzed using voxel-based morphometry approach. Pearson's correlation between spinal cord morphometrics and altered brain GMV and Spearman's relationship between remote neurodegenerations and clinical outcomes were conducted in CSM group. Compared to HCs, CSA and WMA at C2/3 and GMV in right postcentral gyrus (PoCG.R) and left supplementary motor area (SMA.L) were significantly decreased in patients with CSM. CSA and WMA at C2/3 were associated with GMV in SMA.L and MCG.R in patients with CSM. CSA at C2/3 and GMV in PoCG.R were related to modified Japanese Orthopedic Association score in patients with CSM. The associations between CSA and WMA at C2/3 and GMV in SMA.L and MCG.R suggest a concordant change pattern and adaptive mechanisms for neuronal plasticity underlying remote neurodegeneration in early CSM. The atrophy of CSA at C2/3 and GMV loss in PoCG.R can serve as potential neuroimaging biomarkers of early structural changes within spinal cord and brain preceding marked clinical disabilities in patients with CSM.

Condition of the cardiovascular system in Wistar rats with experimental renal dysfunction

The aim: to evaluate functional and structural changes in blood vessels and myocardium in Wistar rats at different stages of the formation of experimental kidney dysfunction.Materials and Methods. Four groups of animals were studied. The first two groups consisted of rats subjected to 5/6 nephrectomy (NE). The period after NE is 2 or 4 months. The third and fourth groups included sham-operated (SO) animals of a similar observation period. After the end of the experiment, blood pressure was measured in rats, the left ventricular mass index (LVMI) was calculated, a biochemical blood test, histological, immunohistochemical and electron microscopic examination of the myocardium were performed, and the contractile activity of the portal vein was recorded for a period of 2 months (in vitro).Results. 2 months after NE, an increase in blood pressure, LVMI, and a decrease in the autorhythmic contractile activity of the portal vein were detected in rats. At the histological level, thickening of cardiomyocytes and arterial vessel walls and the presence of perivascular fibrosis were noted. After 4 months, in rats with NE, the increase in blood pressure, cardiomyocyte hypertrophy and perivascular fibrosis progressed. The thickness of cardiomyocytes was 14.1±3.11 μm, which was significantly greater than in the group with NE for 2 months (12.5±1.5 μm; p=0.008). At this period of observation, electron microscopic examination revealed deintegration of myofibrils, disruption of myofibril stacking and z-disk structure, and changes in the shape of mitochondria. 2 months after NE, an increase in the area of open capillaries was detected in rats (1902.8±202.9 μm²) compared to the corresponding LO animals (730.4±58.2 μm²; p=0.000). As renal dysfunction develops, the capillary area tends to increase (2139.1±396.5 μm²; p =0.120).Conclusion. In Wistar rats with renal dysfunction, changes were detected not only in the level of blood pressure, but also in the functional activity of the intravenous fluid, as well as in the structural components of the myocardium – cardiomyocytes, stroma and blood vessels. The increase in myocardial mass at the histological level was manifested by a significant increase in the thickness of cardiomyocytes, the volume of connective tissue, and the thickness of the wall of arterial vessels, reaching a maximum value at a longer period after NE.

Synthesis of β-cyclodextrin derivatives substituted at larger or smaller rims via amine-catalyzed ring-opening oligomerization of ε-caprolactone

The involvement of cyclodextrins in transesterification reactions with active esters has been described to mimic enzyme-catalyzed reactions, making cyclodextrin molecules suitable as enzyme models. Cyclodextrin-catalyzed ring-opening of cyclic esters in bulk reaction conditions was considered to proceed similarly. However, the mechanism of activating cyclic esters through inclusion in the cyclodextrin cavity remains incompletely understood to date. The present research is focused on observing the transesterification of ε-caprolactone in the presence of β-cyclodextrin and additional amine organocatalysts within dimethyl sulfoxide solutions. The conducted experiments provide insights into the structural changes caused by various catalytic conditions in terms of the substitution pattern of the cyclodextrins. Our results are supported by a deep structural characterization through NMR and MALDI MS, which revealed the prospect of promoting rim-selective substitution of β-cyclodextrin at either secondary or primary hydroxyl groups using 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) organocatalysts. This offers the possibility to prepare cyclodextrin derivatives with specific substitution patterns. Based on the acquired structural information, the particular pathway in which β-cyclodextrin influences the ring-opening of ε-caprolactone is delineated as follows: monomer complexation, substitution at the larger rim, chain elongation, and intramolecular transfer toward the smaller rim.

Ercc1 DNA repair deficiency results in vascular aging characterized by VSMC phenotype switching, ECM remodeling, and an increased stress response.

Cardiovascular diseases are the number one cause of death globally. The most important determinant of cardiovascular health is a person's age. Aging results in structural changes and functional decline of the cardiovascular system. DNA damage is an important contributor to the aging process, and mice with a DNA repair defect caused by Ercc1 deficiency display hypertension, vascular stiffening, and loss of vasomotor control. To determine the underlying cause, we compared important hallmarks of vascular aging in aortas of both Ercc1Δ/- and age-matched wildtype mice. Additionally, we investigated vascular aging in 104 week old wildtype mice. Ercc1Δ/- aortas displayed arterial thickening, a loss of cells, and a discontinuous endothelial layer. Aortas of 24 week old Ercc1Δ/- mice showed phenotypical switching of vascular smooth muscle cells (VSMCs), characterized by a decrease in contractile markers and a decrease in synthetic markers at the RNA level. As well as an increase in osteogenic markers, microcalcification, and an increase in markers for damage induced stress response. This suggests that Ercc1Δ/- VSMCs undergo a stress-induced contractile-to-osteogenic phenotype switch. Ercc1Δ/- aortas showed increased MMP activity, elastin fragmentation, and proteoglycan deposition, characteristic of vascular aging and indicative of age-related extracellular matrix remodeling. The 104 week old WT mice showed loss of cells, VSMC dedifferentiation, and senescence. In conclusion, Ercc1Δ/- aortas rapidly display many characteristics of vascular aging, and thus the Ercc1Δ/- mouse is an excellent model to evaluate drugs that prevent vascular aging in a short time span at the functional, histological, and cellular level.