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Understanding the shear-induced dilatancy of rock fractures is important for assessing the permeability evolution and seismic hazard in shale and geothermal reservoirs. The displacement dependence of fracture dilation has been well studied, while the influence of slip velocity is poorly constrained. In this study, we combined displacement- and velocity-dependent aperture models to reproduce the transient shear-induced dilatancy of fractures in sandstone in 16 normal stress unloading tests. Our results show that the combined aperture model can describe the transient fracture aperture evolution during accelerating slip induced by normal stress unloading better than the model dependent only on slip displacement. Slip velocity could enhance the aperture increase on smoother fractures at lower normal stresses and higher slip velocities. Both the dilation factor and characteristic slip distance decrease with increasing normal stress and surface roughness, signifying reduced contribution of slip velocity to transient shear-induced dilatancy at higher normal stresses and surface roughness. The dilation angle increases with the increase of surface roughness, and this increase diminishes at higher normal stresses primarily attributable to more severe asperity wear. These findings highlight the importance of slip velocity in controlling the transient evolution of aperture and permeability of a rock fracture. Our study also provides constraints on the constitutive parameters in the combined aperture model for describing transient shear-induced fracture dilatancy. We suggest that it is crucial to incorporate the velocity-dependent aperture model to simulate the nonlinear evolution of fracture aperture in future analytical and numerical models involving coupled hydromechanical processes in geoenergy systems. [ABSTRACT FROM AUTHOR]

Red blood cell (RBC) transfusions facilitate many life-saving acute and chronic interventions. Transfusions are enabled through the gold-standard hypothermic storage of RBCs. Today, the demand for RBC units is unfulfilled, partially due to the limited storage time, 6 weeks, in hypothermic storage. This time limit stems from high metabolism-driven storage lesions at +1-6 °C. A recent and promising alternative to hypothermic storage is the supercooled storage of RBCs at subzero temperatures, pioneered by our group. Here, we report on long-term supercooled storage of human RBCs at physiological hematocrit levels for up to 23 weeks. Specifically, we assess hypothermic RBC additive solutions for their ability to sustain supercooled storage. We find that a commercially formulated next-generation solution (Erythro-Sol 5) enables the best storage performance and can form the basis for further improvements to supercooled storage. Our analyses indicate that oxidative stress is a prominent time- and temperature-dependent injury during supercooled storage. Thus, we report on improved supercooled storage of RBCs at −5 °C by supplementing Erythro-Sol 5 with the exogenous antioxidants, resveratrol, serotonin, melatonin, and Trolox. Overall, this study shows the long-term preservation potential of supercooled storage of RBCs and establishes a foundation for further improvement toward clinical translation. This study explores the premise of extended – up to 23 weeks – supercooled storage of human red blood cells in modern and traditional hypothermic additive solutions and the impact of antioxidant supplementation, in comparison to hypothermic storage. [ABSTRACT FROM AUTHOR]

Accurate mechanical measurements of cells has the potential to improve diagnostics, therapeutics and advance understanding of disease mechanisms, where high-resolution mechanical information can be measured by deforming individual cells. Here we evaluate recently developed techniques for measuring cell-scale stiffness properties; while many such techniques have been developed, much of the work examining single-cell stiffness is impacted by difficulties in standardization and comparability, giving rise to large variations in reported mechanical moduli. We highlight the role of underlying mechanical theories driving this variability, and note opportunities to develop novel mechanotyping devices and theoretical models that facilitate convenient and accurate mechanical characterisation. Moreover, many highthroughput approaches are confounded by factors including cell size, surface friction, natural population heterogeneity and convolution of elastic and viscous contributions to cell deformability. We nevertheless identify key approaches based on deformability cytometry as a promising direction for further development, where both high-throughput and accurate single-cell resolutions can be realized. [ABSTRACT FROM AUTHOR]

The deformability of red blood cells (RBCs), expressing their ability to change their shape as a function of flow-induced shear stress, allows them to optimize oxygen delivery to the tissues and minimize their resistance to flow, especially in microcirculation. During physiological aging and blood storage, or under external stimulations, RBCs undergo metabolic and structural alterations, one of which is hemoglobin (Hb) redistribution between the cytosol and the membrane. Consequently, part of the Hb may attach to the cell membrane, and although this process is reversible, the increase in membrane-bound Hb (MBHb) can affect the cell's mechanical properties and deformability in particular. In the present study, we examined the correlation between the MBHb levels, determined by mass spectroscopy, and the cell deformability, determined by image analysis. Six hemoglobin subunits were found attached to the RBC membranes. The cell deformability was negatively correlated with the level of four subunits, with a highly significant inter-correlation between them. These data suggest that the decrease in RBC deformability results from Hb redistribution between the cytosol and the cell membrane and the respective Hb interaction with the cell membrane. [ABSTRACT FROM AUTHOR]

Human pluripotent stem cell (hPSC)-derived red blood cells (RBCs) possess great potential for compensating shortages in transfusion medicine. For better RBC generation from hPSCs, we compared the cell seeding density in the embryoid body formation-based hPSC induction protocol. In the selection of low- and high-density inoculation conditions, we found that low-density culture performed better in the final RBC product with more cell output and increased average cellular hemoglobin content. An elaborate study using flow cytometry demonstrated that low inoculation density promoted endothelial-to-hematopoietic transition, followed by improved hematopoietic progenitor formation and erythrocyte generation. The improved transformation from glycolysis to mitochondrial oxidation and reduced apoptosis might be responsible for this effect. Hints from RNA sequencing suggested that molecules involved in microenvironment interaction and metabolic regulation might respond for the different developmental potential. The possible mediators between outer message and intracellular response could be the nutrition sensors FOXO, PRKAA1 (AMPK), and MTOR genes. It is possible that low inoculation density triggered metabolic regulation signals, promoted mitochondrial oxidation, and resulted in enhanced cell amplification and hematopoietic differentiation. The low cell culture density will improve RBC generation from hPSCs. [ABSTRACT FROM AUTHOR]

Our group generated two induced pluripotent stem cell (iPSC) lines for in vitro red blood cell (RBC) production from blood donors with extensively known erythrocyte antigen profiles. One line was intended to give rise to RBCs for transfusions in patients with sickle cell disease (SCD), while the other was developed to create RBC panel reagents. Two blood donors were selected based on their RBC phenotypes, further complemented by high-throughput DNA array analysis to obtain a more comprehensive erythrocyte antigen profile. Enriched erythroblast populations from the donors' peripheral blood mononuclear cells were reprogrammed into iPSCs using nonintegrative plasmid vectors. The iPSC lines were characterized and subsequently subjected to hematopoietic differentiation. iPSC PB02 and iPSC PB12 demonstrated in vitro and in vivo iPSC features and retained the genotype of each blood donor's RBC antigen profile. Colony-forming cell assays confirmed that iPSC PB02 and iPSC PB12 generated hematopoietic progenitors. These two iPSC lines were generated with defined erythrocyte antigen profiles, self-renewal capacity, and hematopoietic differentiation potential. With improvements in hematopoietic differentiation, these cells could potentially be more efficiently differentiated into RBCs in the future. They could serve as a complementary approach for obtaining donor-independent RBCs and addressing specific demands for blood transfusions. [ABSTRACT FROM AUTHOR]

α-Synuclein (α-Syn) is a protein related to synucleinopathies with high expression in the central nervous system and erythrocytes which are a major source of peripheral α-Syn. Recent reports have suggested the presence of α-Syn within extracellular vesicles (EVs) derived from erythrocytes, potentially contributing to the pathogenesis of synucleinopathies. While Lewy bodies, intracellular inclusions containing aggregated α-Syn, are prominently observed within the brain, their occurrence in peripheral neurons implies the dissemination of synucleinopathy pathology throughout the body via the propagation of α-Syn. In this study, we found erythrocytes and circulating EVs obtained from plasma contained α-Syn, which was separated into four major forms using high-resolution clear native-PAGE and isoelectric focusing. Notably, erythrocyte α-Syn was classified into full-length and C-terminal truncated forms, with truncation observed between Y133 and Q134 as determined by LC–MS/MS analysis. Our finding revealed that C-terminally truncated α-Syn, which was previously reported to exist solely within the brain, was also present in erythrocytes and circulating EVs obtained from plasma. [ABSTRACT FROM AUTHOR]

Fabric‐reinforced shape memory polymer composites are lightweight, strong, formable, controllable, and suitable for various engineering and innovative applications. This study aims to fabricate and characterize electrothermal dual drive shape memory polymer composite fabrics (SMPCFs) of different densities with three‐dimensional (3D) angle‐interlock structures. The tensile properties, electrothermal properties, recovery forces (both tensile and bending), and shape recovery properties of SMPCFs were evaluated. The SMPCFs exhibited a tensile elongation of over 20% at the transition temperature. SMPCFs can reach transition temperatures when loaded with 2 V. The recovery forces are up to 225 N in tensile recovery force and 3.6 N in bending recovery force. In the shape recovery test, the recovery ratio exceeded 97%. Finally, the demonstration of recovery properties can stimulate the possibilities of SMPCFs in innovation and applications. Highlights: Core‐shell structured composite filaments were prepared.3D angle‐interlock composite fabrics: high strength, electrothermal drive.Tensile recovery force of composite fabrics can be up to 225 N.Elongation at transition temperatures was up to 20%. [ABSTRACT FROM AUTHOR]

BACKGROUND: The triad "insulin resistance, prediabetes, diabetes" is three independent neologies with characteristic features and development. In addition, each are characterized by progression and the possibility of transition from one form to other. Due to the fact that diabetes is one of the common diseases associated with high rates of disability, it is necessary to improve diagnostic methods and educational regimens for successful prevention and treatment of the disease. OBJECTIVE: We investigated Band 3 protein (B3p) level, osmotic resistance of erythrocytes, the total antioxidant activity (TAA) of blood serum, level of HbA1 in group patients with insulin resistance (IR), prediabetes, and Type 2 Diabetes Mellitus (T2DM) and comparative with health control group. METHODS: We used original, accurate research methods that measure the essence of the studied quantities. RESULTS: Disruptions of glucose and insulin homeostasis ay lead to the initiation of oxidative stress (in our study demonstrated by a decrease of TAA of blood serum) increased redox-sensitive PTP activity and aberrant band 3 phosphorylation, potentially leading to reduced erythrocyte deformability. At the same time glycation of Hb during T2DM may affect its cross-link with membrane proteins, in particular with B3p, and although appears to limit its cross-linking and decrease its clusterization ability, induces alterations in the cytoskeletal matrix, and thereby decrease erythrocytes' osmotic resistance making them more susceptible to hemolysis. CONCLUSIONS: The osmotic resistance of the erythrocytes can be used as a sensitive marker for the detection of the early stages of hyperglycemia (prediabetes). This set of clinical trials will make it possible to identify diseases that make up the triad at an early stage. Early detection of disorders and continued research in this direction will help in the development of a diagnostic scheme for the prevention of such patients. Based on our data, research into anti-oxidation drugs is very important. With the help of the array of studies described in the article and antioxidant treatment, the likelihood of successful treatment will increase. [ABSTRACT FROM AUTHOR]

The current paper is aimed to investigate the deformability effects of the bearing surface on the lubrication performance of cylindrical journal bearing with finite length under turbulent conditions. The bush is coated with a thin resilient layer with a smooth surface, the radial distortions of which are of the same order of magnitude as the film thickness. The elastohydrodynamic problem is studied under elasticity conditions in accordance with the plain strain hypothesis (Winkler model). The modified Reynolds equation is carried out on the base of the turbulent lubrication model of Hirs (bulk flow model). The partial differential equation is solved numerically by successive over-relaxation technique on a finite difference grid, considering different values of coating materials, lubricant viscosity, and journal speed. Results for the performance characteristics of the bearing are given for several selected values of Reynolds number and elasticity parameters of the soft liner on the bush. [ABSTRACT FROM AUTHOR]

Measurements of neutron star mass and radius or tidal deformability deliver unique insight into the equation of state (EOS) of cold dense matter. EOS inference is very often done using generalized parametric or non-parametric models, which deliver no information on composition. In this paper, we consider a microscopic nuclear EOS model based on a field theoretical approach. We show that current measurements from NICER and gravitational wave observations constrain primarily the symmetric nuclear matter EOS. We then explore what could be delivered by measurements of mass and radius at the level anticipated for future large-area X-ray timing telescopes. These should be able to place very strong limits on the symmetric nuclear matter EOS, in addition to constraining the nuclear symmetry energy that determines the proton fraction inside the neutron star. [ABSTRACT FROM AUTHOR]

Cold water immersion (CWI) involves rapid cooling of the body, which, in healthy individuals, triggers a defence response to an extreme stimulus, to which the body reacts with stress. The aim of the study was to determine the effect of CWI on hemorheological blood indicators. The study group consisted of 13 young males. Blood samples were collected before and after CWI. The assessed parameters included the complete blood count, fibrinogen, hs-C-reactive protein (CRP), proteinogram, and blood rheology factors, such as erythrocyte elongation index (EI), half-time of total aggregation, and aggregation index. Additionally, the effect of reduced temperature on primary human vascular endothelium was investigated in vitro. CWI resulted in the decrease of body temperature to 31.55 ± 2.87 °C. After CWI, neutrophil count and mean corpuscular volume (MCV) were significantly increased in the study group, while lymphocyte count was significantly decreased. Significantly higher levels of total blood protein and albumin concentration were detected after the immersion. Among hemorheological characteristics, erythrocyte EIs at shear stress values ranging from 2.19 to 60.30 Pa were significantly lower after CWI. No significant changes in other rheological, morphological or biochemical parameters were observed. In vitro, human umbilical vein endothelial cells responded to 3 h of temperature decrease to 25 °C with unchanged viability, but increased recruitment of THP-1 monocytic cells and changes in cell morphology were observed. This was the first study to evaluate the effect of single CWI on rheological properties of blood in healthy young men. The results indicate that a single CWI may increase blood protein concentrations and worsen erythrocyte deformability parameters. [ABSTRACT FROM AUTHOR]

Introduction: Equations can calculate pulse wave velocity (ePWV) from blood pressure values (BP) and age. The ePWV predicts cardiovascular events beyond carotid-femoral PWV. We aimed to evaluate the correlation between four different equations to calculate ePWV. Methods: The ePWV was estimated utilizing mean BP (MBP) from office BP (MBPOBP) or 24-hour ambulatory BP (MBP24-hBP). We separated the whole sample into two groups: individuals with risk factors and healthy individuals. The e-PWV was calculated as follows: e 1 − P W V = 9.58748315543126 − 0.402467539733184 * age + 4.56020798207263 * 10 − 3 * age 2 − 2.6207705511664 * 10 − 5 *age 2 * MBP + 3.1762450559276 * 10 − 3 * age * MBP − 1.83215068503821 * 10 − 2 * MBP e 2 − P W V = 4.62 − 0.13 * age + 0.0018 * age 2 + 0.0006 * age * MBP + 0.0284 * MBP We calculated the concordance correlation coefficient (Pc) between e1-PWVOBP vs e2-PWVOBP, e1-PWV24-hBP vs e2-PWV24-hBP, and mean values of e1-PWVOBP, e2-PWVOBP, e1-PWV24-hBP and e2-PWV24-hBP. The multilevel regression model determined how much the ePWVs are influenced by age and MBP values. Results: We analyzed data from 1541 individuals; 1374 ones with risk factors and 167 healthy ones. The values are presented for the entire sample, for risk-factor patients and for healthy individuals respectively. The correlation between e1-PWVOBP with e2-PWVOBP and e1-PWV24-hBP with e2-PWV24-hBP was almost perfect. The Pc for e1-PWVOBP vs e2-PWVOBP was 0.996 (0.995–0.996), 0.996 (0.995–0.996), and 0.994 (0.992–0.995); furthermore, it was 0.994 (0.993–0.995), 0.994 (0.994–0.995), 0.987 (0.983–0.990) to the e1-PWV24-hBP vs e2-PWV24-hBP. There were no significant differences between mean values (m/s) for e1-PWVOBP vs e2-PWVOBP 8.98±1.9 vs 8.97±1.8; p = 0.88, 9.14±1.8 vs 9.13±1.8; p = 0.88, and 7.57±1.3 vs 7.65±1.3; p = 0.5; mean values are also similar for e1-PWV24-hBP vs e2-PWV24-hBP, 8.36±1.7 vs 8.46±1.6; p = 0.09, 8.50±1.7 vs 8.58±1.7; p = 0.21 and 7.26±1.3 vs 7.39±1.2; p = 0.34. The multiple linear regression showed that age, MBP, and age2 predicted more than 99.5% of all four e-PWV. Conclusion: Our data presents a nearly perfect correlation between the values of two equations to calculate the estimated PWV, whether utilizing office or ambulatory blood pressure. [ABSTRACT FROM AUTHOR]

SCD is a hereditary disorder caused by genetic mutation in the beta-globin gene, resulting in abnormal hemoglobin, HbS that forms sickle-shaped erythrocytes under hypoxia. Patients with SCD have endocrine disorders and it was described that 7% of these patients have clinical hypothyroidism. Recent studies have shown that mature erythrocytes possess TSH receptors. Thus, we aimed to assess the effects of TSH on SCD erythrocytes. The experiments were conducted using different concentrations of TSH (1, 2, 3, and 5 mIU/L). In HbS polymerization assay, erythrocytes were exposed to TSH in hypoxia to induce polymerization, and measurements were taken for 30 minutes. The deformability assay was made using Sephacryl-S 500 columns to separate deformable from nondeformable cells. Static adhesion test utilized thrombospondin to assess erythrocyte adhesion in the presence of TSH. TSH at all contractions were able to reduce polymerization of HbS and increase deformability. The static adhesion of erythrocytes at the lowest concentrations of 1 and 2 mIU/L were increased, but at higher contractions of 3 and 5 mIU/L, static adhesion was not modulated. The results suggest that TSH has potential involvement in the pathophysiology of sickle cell disease by inhibiting HbS polymerization, positively modulating deformability and impacting static adhesion to thrombospondin. [ABSTRACT FROM AUTHOR]

In severe cases, SARS-CoV-2 infection leads to severe respiratory failure. Although angiotensin-converting enzyme 2 (ACE2) receptors are not expressed in red blood cells, SARS-CoV-2 can interact with red blood cells (RBCs) via several receptors or auxiliary membrane proteins. Recent data show that viral infection causes significant damage to the RBCs, altering their morphology, deformability, and aggregability. Loss of RBC deformability and/or increased aggregability favors the development of thrombotic processes in the microcirculation, as has been described to occur in COVID-19 patients. In addition, many patients also develop systemic endotheliitis associated with generalized coagulopathy. This manifests itself clinically as obstructive microthrombi in the area of the medium and smallest vessels, which can affect all internal organs. It is thought that such changes in the RBCs may contribute to the microangiopathy/microthrombosis associated with COVID-19 and may result in impaired capillary blood flow and tissue oxygenation. [ABSTRACT FROM AUTHOR]

Absorption spectra of red blood cell (RBC) suspensions are investigated in an osmolarity range in the medium from 200 mOsm to 900 mOsm. Three spectral parameters are used to characterize the process of swelling or shrinkage of RBC—the absorbance at 700 nm, the Soret peak height relative to the spectrum background, and the Soret peak wavelength. We show that with an increase in the osmolarity, the absorbance at 700 nm increases and the Soret peak relative height decreases. These changes are related to the changes in the RBC volume and the resulting increase in the hemoglobin intracellular concentration and index of refraction. Confocal microscopy and flow cytometry measurements supported these conclusions. The maximum wavelength of the Soret peak increases with increasing osmolarity due to changes in the oxygenation state of hemoglobin. Using these spectrum parameters, the process of osmosis in RBCs can be followed in real time, but it can also be applied to various processes, leading to changes in the volume and shape of RBCs. Therefore, we conclude that UV–Vis absorption spectrophotometry offers a convenient, easily accessible, and cost-effective method to monitor changes in RBC, which can find applications in the field of drug discovery and diagnostics of RBC and hemoglobin disorders. [ABSTRACT FROM AUTHOR]

Toxicity caused by carbon tetrachloride (CCl4) can lead to serious liver injury. The aim of the study is to investigate the protective effects of oregano oil (Origanum minutiflorum extract oil) against CCl4‐induced liver injury. Two doses of oregano oil were used in the experiment: a low dose (LD; 20 mg/kg) and a high dose (HD; 60 mg/kg) during 2 weeks. CCl4 caused severe liver damage, nucleolus destruction in hepatocytes and cytogenetic changes in the nucleus. Indirectly, CCl4 causes decreased protein synthesis and significantly high creatinine and urea values. Hematological disorders have been recorded, such as decreased RBC and hemoglobin concentration, increased WBC and deformability of the erythrocyte membrane. Both doses of oregano oil had protective effects. Improved protein synthesis and high globulins level, creatinine and urea were found in both groups. Cytogenetic changes in the nucleus of hepatocytes were reduced. A high dose of oregano oil had maximal protective effects for RBC, but a very weak effect on hemoglobin synthesis. Also, WBC and lymphocyte values were low. Origanum stimulates protein synthesis and recovery of hepatocytes after liver injury, reduces the deformability of the erythrocyte membrane. High doses of oregano oil decreased WBC and lymphocytes which may lead to a weakening of the immune response. However, high doses are more effective against severe platelet aggregation than low doses, suggesting an effective treatment against thrombocytosis. Significance statement: Oregano oil extract is a powerful antioxidant and is hepatoprotective. High doses had strong effects against carbon tetrachloride‐induced thrombocytosis, but significantly lowered leukocytes and lymphocytes, which can lead to weakened immunity. For the maximum effect of oreiganum oil, it is necessary to determine the optimal doses and daily intake. This study will contribute to the literature in terms of the discovery of possible effects of oregano oil treatment in pathology related to liver injury and hematological disorders. [ABSTRACT FROM AUTHOR]

In this paper, Polyethylene Terephthalate Glycol (PETG) has been used as a novel thermoplastic thermo-responsive Shape Memory Polymer (SMP) with biocompatibility, excellent printability, cost efficiency, and transparency for the 3D/4D printing of porous structures by material extrusion. The high deformability of PETG allows for programming without an increase in temperature or the need for additional operations. This enabled the use of PETG for the Cold Programming (CP) of ordered porous shape memory structures, made possible by material extrusion printing technology. The porous samples were printed employing three patterns and two porosity percentages. The programming operation was performed at ambient temperature by applying different amounts of pre-strains under constrained and unconstrained compression modes. The constrained test was conducted using a mandrel and a matrix for exerting pure volume reduction (pure packing). The shape recovery test was accomplished above the glass transition temperature (Tg), and the fixity and recovery ratios were recorded. Employing 3D printing provided the ability to manufacture porous thermoplastic SMP structures with highly controllable pores geometry and sizes for different porosity percentages. The results showed that the combination of the uniform strain distribution in the porous structures with the help of the 3D printing process and CP on the new PETG SMP makes it possible to achieve high deformation in the glassy region, resulting in a complete shape recovery for two lozenge and vertical patterns. Among all specimens, constrained specimens by horizontal pattern had the highest fixity ratio of 90.7%. However, low fixity ratios in CP can be justified considering the existence of two stages of spring-back and structural relaxation after unloading, resulting from the elastic and viscoelastic behavior. Increasing Infill Density (ID) along with the constrained test (pure packing) improved the shape fixity. The existence of higher mechanical constraints and harsher localized deformation are speculated to be the case for this observation. Applying higher deformations (40 to 80%), for both designed tests, brought about a weakness in the shape memory performance, while it improved for 100% volume reduction. [ABSTRACT FROM AUTHOR]

Lipid bilayer membranes such as liposomes have been utilized as platforms for bioinspired artificial photosynthesis. Embedding functional compounds, including chromophores and catalysts, into two‐dimensional lipid membranes allows their high local concentration and proximity, resulting in enhanced reactivity compared to that of homogeneous solutions. The control of photoreactions by the physical and chemical properties of membranes, such as fluidity and phase separation, has also been well studied in recent years. In contrast, it remains difficult to control chemical reactions via dynamic membrane deformation. Here, we report on the control of excitation energy transfer using red blood cell ghosts (RBCGs) as scaffolds, relying on their asymmetric lipid membranes and inherent and unique deformability. RBCGs, in which donor and acceptor molecules were chemically conjugated to a two‐dimensional cytoskeleton located beneath the inner membrane, exhibited energy transfer, and their efficiency varied depending on the amount and ratio of donor and acceptor modifications, as confirmed by experimental and theoretical analysis. Furthermore, the KCl concentration‐induced RBCG shrinkage enhanced the energy transfer efficiency. Our proposed method is expected to facilitate the construction of photoreaction systems that can be controlled via membrane deformation. [ABSTRACT FROM AUTHOR]

Exposure to both oxidative and shear stress, a condition that the red blood cell (RBC) continuously experiences in the circulation in vivo can be mimicked in a Couette type viscometer and monitored by ektacytometry. RBCs maintain their deformation and orientation under shear stress and oxidative stress until a threshold is reached at which these conditions appear to overwhelm the elaborate and complex pathways that maintain a proper redox environment in the cell. Oxidative stress under shear alters the ability of the cell to deform, changes cell morphology, its orientation in the shear stress field, and appears to alter intracellular and membrane characteristics. The application of the RoxyScan technology allows the comparison of oxidant effects and the role of antioxidant systems. This provides the opportunity to study the ability of RBC to deal with oxidative stress in various conditions, including RBC disorders such as sickle cell disease (SCD). [ABSTRACT FROM AUTHOR]

Intracellular signaling mechanisms in red blood cells (RBCs) involve various protein kinases and phosphatases and enable rapid adaptive responses to hypoxia, metabolic requirements, oxidative stress, or shear stress by regulating the physiological properties of the cell. Protein phosphorylation is a ubiquitous mechanism for intracellular signal transduction, volume regulation, and cytoskeletal organization in RBCs. Spectrin‐based cytoskeleton connects integral membrane proteins, band 3 and glycophorin C to junctional proteins, ankyrin and Protein 4.1. Phosphorylation leads to a conformational change in the protein structure, weakening the interactions between proteins in the cytoskeletal network that confers a more flexible nature for the RBC membrane. The structural organization of the membrane and the cytoskeleton determines RBC deformability that allows cells to change their ability to deform under shear stress to pass through narrow capillaries. The shear stress sensing mechanisms and oxygenation‐deoxygenation transitions regulate cell volume and mechanical properties of the membrane through the activation of ion transporters and specific phosphorylation events mediated by signal transduction. In this review, we summarize the roles of Protein kinase C, cAMP‐Protein kinase A, cGMP‐nitric oxide, RhoGTPase, and MAP/ERK pathways in the modulation of RBC deformability in both healthy and disease states. We emphasize that targeting signaling elements may be a therapeutic strategy for the treatment of hemoglobinopathies or channelopathies. We expect the present review will provide additional insights into RBC responses to shear stress and hypoxia via signaling mechanisms and shed light on the current and novel treatment options for pathophysiological conditions. [ABSTRACT FROM AUTHOR]

The ability to change shape is essential for the proper functioning of red blood cells (RBCs) within the microvasculature. The shape of RBCs significantly influences blood flow and has been employed in microfluidic lab-on-a-chip devices, serving as a diagnostic biomarker for specific pathologies and enabling the assessment of RBC deformability. While external flow conditions, such as the vessel size and the flow velocity, are known to impact microscale RBC flow, our comprehensive understanding of how their shape-adapting ability is influenced by channel confinement in biomedical applications remains incomplete. This study explores the impact of various rectangular and square channels, each with different confinement and aspect ratios, on the in vitro RBC flow behavior and characteristic shapes. We demonstrate that rectangular microchannels, with a height similar to the RBC diameter in combination with a confinement ratio exceeding 0.9, are required to generate distinctive well-defined croissant and slipper-like RBC shapes. These shapes are characterized by their equilibrium positions in the channel cross section, and we observe a strong elongation of both stable shapes in response to the shear rate across the different channels. Less confined channel configurations lead to the emergence of unstable other shape types that display rich shape dynamics. Our work establishes an experimental framework to understand the influence of channel size on the single-cell flow behavior of RBCs, providing valuable insights for the design of biomicrofluidic single-cell analysis applications. [ABSTRACT FROM AUTHOR]

Combined radiation with hemorrhage (combined injury, CI) exacerbates hematopoietic acute radiation syndrome and mortality compared to radiation alone (RI). We evaluated the effects of RI or CI on blood cell depletion as a biomarker to differentiate the two. Male CD2F1 mice were exposed to 8.75 Gy γ-radiation (60Co). Within 2 h of RI, animals were bled under anesthesia 0% (RI) or 20% (CI) of total blood volume. Blood samples were collected at 4–5 h and days 1, 2, 3, 7, and 15 after RI. CI decreased WBC at 4–5 h and continued to decrease it until day 3; counts then stayed at the nadir up to day 15. CI decreased neutrophils, lymphocytes, monocytes, eosinophils, and basophils more than RI on day 1 or day 2. CI decreased RBCs, hemoglobin, and hematocrit on days 7 and 15 more than RI, whereas hemorrhage alone returned to the baseline on days 7 and 15. RBCs depleted after CI faster than post-RI. Hemorrhage alone increased platelet counts on days 2, 3, and 7, which returned to the baseline on day 15. Our data suggest that WBC depletion may be a potential biomarker within 2 days post-RI and post-CI and RBC depletion after 3 days post-RI and post-CI. For hemorrhage alone, neutrophil counts at 4–5 h and platelets for day 2 through day 7 can be used as a tool for confirmation. [ABSTRACT FROM AUTHOR]

Plant-derived chemicals are promising substances to control arthropod pests, although synthetic ones are still the most frequently used. Thus, comparative toxicological studies are needed to determine if natural substances are safe alternatives to replace the use of synthetic chemicals. This study aimed to compare the toxicity of carvacrol (natural origin), acetylcarvacrol (semi-synthetic) and a fipronil-based pesticide (synthetic). We assessed the effects of these chemicals on hemolytic activity, erythrocytes morphology and leucocyte viability using whole blood from human subjects. Additionally, DNA damage was evaluated through comet and DNA fragmentation assays. Fipronil and carvacrol caused hemolysis at concentrations ranging from 0.5 to 2.0%, whereas acetylcarvacrol did not cause hemolysis at 0.5 and 0.75%. Fipronil and carvacrol caused severe alterations in erythrocytes' morphology at 2%, such as ghost erythrocytes, elliptocyte-like shape and rouleau-like shape, presenting only 3.3 and 8.3% normal cells, respectively, at this concentration. However, 73.3% erythrocytes incubated with 2% acetylcarvacrol exhibited normal morphology. Fipronil considerably reduced leucocytes viability, decreasing it to 78% at 2%. Carvacrol and acetylcarvacrol showed no differences in leucocyte viability for 0.5 to 1.0%, but a decrease was observed for 2% carvacrol. The comet assay showed similar DNA damage for fipronil and carvacrol, but it was significantly lower for 1 and 2% acetylcarvacrol. Incubation with genomic DNA showed that only fipronil caused fragmentation of this molecule. Thus, we conclude that carvacrol and fipronil can present similar toxicity at higher concentrations. However, acetylation of carvacrol significantly reduced its toxicity to human blood cells compared with the other chemicals. [ABSTRACT FROM AUTHOR]

BACKGROUND: Sand therapy is a non-pharmacological physiotherapy method that uses the natural environment and resources of Xinjiang to treat through the heat transfer and magnetic effects of sand. OBJECTIVE: Employing the two-phase flow-Casson blood flow model, we investigate the mechanism of atherosclerosis prevention via sand therapy, offering a biomechanical theoretical rationale for the prevention of atherosclerosis through sand therapy via the prism of computational fluid dynamics (CFD). METHODS: Sand therapy experiments were conducted to obtain popliteal artery blood flow velocity, and blood was considered as a two-phase flow composed of plasma and red blood cells, and CFD method was applied to analyze the hemodynamic effects of Casson's blood viscosity model before and after sand therapy. RESULTS: (1) The blood flow velocity increased by 0.24 m/s and 0.04 m/s at peak systolic and diastolic phases, respectively, after sand therapy; the axial velocity of blood vessels increased by 28.56% after sand therapy. (2) The average red blood cell viscosity decreased by 0.00014 Pa ⋅ s after sand therapy. (3) The low wall shear stress increased by 1.09 Pa and the high wall shear stress reached 41.47 Pa after sand therapy. (4) The time-averaged wall shear stress, shear oscillation index and relative retention time were reduced after sand therapy. CONCLUSION: The increase of blood flow velocity after sand therapy can reduce the excessive deposition of cholesterol and other substances, the decrease of erythrocyte viscosity is beneficial to the migration of erythrocytes to the vascular center, the increase of low wall shear stress has a positive effect on the prevention of atherosclerosis, and the decrease of time-averaged wall shear stress, shear oscillation index and relative retention time can reduce the occurrence of thrombosis. [ABSTRACT FROM AUTHOR]

Rosetting, the formation of red blood cell aggregates, is a life-threatening condition in malaria tropica and not yet fully understood. We study rosette stability using a set of microfluidic stenotic channels, with varied narrowing angle and erythrocytes of blood groups O and A. We find reduced ability of a rosette to pass a stenosis without disruption, the longer the tapered part of the constriction and the narrower the stenosis is. In general, this ability increases with rosette size and is 5–15% higher in blood group A. The experimental results are substantiated by equivalent experiments using lectin-induced red blood cell aggregates and a simulation of the underlying protein binding kinetics. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is considered to be one of the hematological malignancies formed by excessive and abnormal proliferation of plasmocytes. Among other parameters, several blood tests are used to diagnose multiple myeloma. The hemorheological profile in multiple myeloma is not widely studied. Hemorheology includes the study of measuring the deformability and aggregation of erythrocytes, blood viscosity, and sedimentation rate. The degree of deformability of blood cells is necessary to maintain proper vital functions. Proper deformability of red blood cells ensures proper blood circulation, tissue oxidation and carbon dioxide uptake. The aim of the study was to compare morphology and blood rheology parameters in patients with MM and healthy individuals. The study included 33 patients with MM, and 33 healthy subjects of the same age. The hematological blood parameters were evaluated using ABX MICROS 60 hematology analyzer. The LORCA Analyzer to study erythrocyte aggregation and deformability. Patients with MM had lower red blood cells count (RBC) (9.11%) (p < 0.001) and half time of total aggregation (T1/2) (94.29%) (p < 0.001) values and higher mean corpuscular volume (MCV) (5.50%) (p < 0.001), aggregation index (AI) (68.60%) (p < 0.001), total extent of aggregation (AMP) (87.92%) (p < 0.001) values than the healthy control group. Aggregation in patients with MM is different compared to healthy individuals. It was observed that the percentage of cell aggregation is almost 50% higher than in the control group. The study of morphology, aggregation and deformability of erythrocytes in patients with suspected MM may be helpful in making clinical decisions. [ABSTRACT FROM AUTHOR]

This document is an editorial introducing a special issue on advances in red blood cell research. The collection of articles covers a range of topics, including molecular mechanisms of pathologies, novel diagnostic approaches, case studies, epidemiological studies, and transfusion medicine. The articles explore factors influencing red blood cell production, rheological properties of red blood cells, and the use of red blood cells as biomarkers for various diseases. The document also discusses the potential for functional tests and technological advancements in red blood cell research. Additionally, it highlights the importance of in vitro culturing and preservation of red blood cells for transfusion purposes. The authors express their satisfaction with the completion of the issue and look forward to future developments in the field. [Extracted from the article]

Plasmodium parasites need to find red blood cells (RBCs) that, on the one hand, expose receptors for the pathogen ligands and, on the other hand, maintain the right geometry to facilitate merozoite attachment and entry into the red blood cell. Both characteristics change with the maturation of erythrocytes. Some Plasmodia prefer younger vs. older erythrocytes. How does the life evolution of the RBC affect the invasion of the parasite? What happens when the RBC ages? In this review, we present what is known up until now. [ABSTRACT FROM AUTHOR]

The protein 4.1R is an essential component of the erythrocyte membrane skeleton, serving as a key structural element and contributing to the regulation of the membrane's physical properties, including mechanical stability and deformability, through its interaction with spectrin–actin. Recent research has uncovered additional roles of 4.1R beyond its function as a linker between the plasma membrane and the membrane skeleton. It has been found to play a crucial role in various biological processes, such as cell fate determination, cell cycle regulation, cell proliferation, and cell motility. Additionally, 4.1R has been implicated in cancer, with numerous studies demonstrating its potential as a diagnostic and prognostic biomarker for tumors. In this review, we provide an updated overview of the gene and protein structure of 4.1R, as well as its cellular functions in both physiological and pathological contexts. [ABSTRACT FROM AUTHOR]

In this study, we numerically investigate the collision dynamics of core–shell compound droplet pairs under confined shear flow conditions. We focus on three collision modes: pass-over, coalescence, and reverse-back motions, analyzing their motion trajectories and morphological evolution. Notably, the coalescence mode exhibits significant dynamic behavior during evolution. However, the coalescence behavior of compound droplet pairs, as well as the impact of geometric parameters, including the initial vertical offset of droplets and the degree of confinement, on their dynamic behaviors, remains largely unexplored and unquantified. Our simulation results reveal that core droplets have little effect on the trajectory of droplet pairs during their pass-over and reverse-back motions, yet they significantly affect the dynamics in the coalescence mode. Additionally, we have addressed how the interplay between the core-shell size ratio, initial offset, and wall confinement affects the transition between collision modes, morphology, trajectory, and final state of the droplet pairs. Our findings show that an increase in the core–shell size ratios restricts the deformability of the shell droplets. Furthermore, in the coalescence mode, larger core droplets coalesce more rapidly due to spatial adjustment, expediting the stabilization of the newly formed compound droplet. While the size of the core droplets does not alter the transition boundary from coalescence to reverse-back mode based on initial vertical offset, they significantly influence the transition from coalescence to pass-over mode. Moreover, by analyzing confinement as another crucial geometric factor, we demonstrate the coupling effects of confinement and initial vertical offset on the transition between different collision modes. [ABSTRACT FROM AUTHOR]

Since the discovery of physical peculiarities around transcription start sites (TSSs) and a site corresponding to the TATA box, research has revealed only the average features of these sites. Unsettled enigmas include the individual genes with these features and whether they relate to gene function. Herein, using 10 physical properties of DNA, including duplex DNA free energy, base stacking energy, protein-induced deformability, and stabilizing energy of Z-DNA, we clarified for the first time that approximately 97% of the promoters of 21,056 human protein-coding genes have distinctive physical properties around the TSS and/or position −27; of these, nearly 65% exhibited such properties at both sites. Furthermore, about 55% of the 21,056 genes had a minimum value of regional duplex DNA free energy within TSS-centered ±300 bp regions. Notably, distinctive physical properties within the promoters and free energies of the surrounding regions separated human protein-coding genes into five groups; each contained specific gene ontology (GO) terms. The group represented by immune response genes differed distinctly from the other four regarding the parameter of the free energies of the surrounding regions. A vital suggestion from this study is that physical-feature-based analyses of genomes may reveal new aspects of the organization and regulation of genes. [ABSTRACT FROM AUTHOR]

Hemorheological parameters have been reported to be altered in cardiovascular disease. Major depression has been associated with increased risk of cardiovascular disease. Our hypothesis is that hemorheological parameters are disturbed in major depressive disorder. Major depressive disorder and control groups consisted of 50 subjects. Plasma viscosity, erythrocyte aggregation, erythrocyte deformability, hematological parameters and hematological parameters were examined. Plasma viscosity was statistically significantly higher, erythrocyte elongation index at 0.53 Pa and 0.95 Pa was lower, and MCV, MCH, and MCHC values were also lower in the major depression group (P <  0.05). Elongation index and plasma viscosity were correlated with depressive symptomatology. The increased plasma viscosity and decreased elongation index of erythrocytes indicate an unfavorable hemorheological situation in patients with major depressive disorder compared with healthy controls. The results of this study confirm the findings of studies finding a potential threat to cardiovascular health from major depressive disorder. Increased plasma viscosity and decreased erythrocyte elongation index in depressed patients may be risk factors for cardiovascular events and provide data on the causality of the association between depression and cardiovascular disease. [ABSTRACT FROM AUTHOR]

In this study, Trifluralin (TRF) co-loaded with Miltefosine (MTF) in nano transfersomes (NTs) were prepared aiming their enhanced penetration topically with improved macrophage targeting and antileishmanial effects. Formulations were optimized in a series of experiments based on their particle size, polydispersity index (PDI), drug incorporation and deformability index. TEM analysis was performed to check morphology of NTs. TRF-MTF co-loaded NTs were further incorporated into chitosan gel to obtain better retention. In vitro release and Ex vivo permeation studies of the optimized TRF-MTF co-loaded NTs were conducted to check dissolution behavior and skin permeation of the developed formulation as compared to the drug solutions and TRF-MTF co-loaded NTs gel. Macrophage uptake and antileishmanial efficacy of the developed formulation was also investigated. The optimized formulation had a particle size of 188.5 nm with rounded morphology, PDI of 0.101, and deformability index of 0.987. The drug incorporation of TRF and MTF were respectively found as 91% and 88%. Controlled and significantly enhanced drug release and augmented skin penetration was observed from the TRF-MTF co-loaded NTs as compared to pure drugs. Significant uptake of the TRF-MTF co-loaded NTs by the macrophage proved greater intracellular infiltration via the skin barriers. In vitro anti-leishmanial study exhibited 6-folds and 5-folds decrease in the respective IC50 values of TRF-MTF co-loaded NTs when used against Leishmania (L.) tropica amastigotes and promastigotes. This study exhibited the efficacy of NTs when loaded with dual drugs for enhanced skin penetration and macrophage localization. [ABSTRACT FROM AUTHOR]

Background: Regular exercise elicits adaptive changes in several organs and physiological processes, including erythrocyte properties. Methods: In a group of 79 subjects (62 men and 17 women; mean age 31.37 ± 10.19 years) who trained several times a week as they practiced amateur sports, we evaluated the elongation index, markers of erythrocyte deformability, red blood cell distribution width (RDW), indicators of erythrocyte anisocytosis, hematocrit, hemoglobin, and the main erythrocyte indices (MCV, MCH, MCHC) in basal conditions. Results: In comparison with a group of healthy, but not training, volunteers, the values of the elongation index, and not the RDW, are increased, and this datum is accompanied by an increase in MCV and MCHC, likely related to an increased presence of circulating young erythrocytes in training subjects. We also divided the same group according to the median of the VO2max, observing that the subgroup above the median shows both an increase in the elongation index values and a decrease in MCH and MCHC. Conclusions: In trained subjects, there is no correlation between the values of the elongation index and the RDW, while the interrelations among the elongation index, RDW, and main erythrocyte indices appear to be of particular interest and of a certain complexity. [ABSTRACT FROM AUTHOR]

The manipulation and control of microparticles through non-intrusive methods is pivotal in biomedical applications such as cell sorting and cell focusing. Although several experimental and numerical studies have been dedicated to single suspended particles or clusters of rigid spheres, analogous cases with deformable particles have not been as thoroughly studied, especially when the suspending liquid exhibits relevant viscoelastic properties. With the goal of expanding the current knowledge concerning these systems, we perform a computational study on the hydrodynamic interactions between two neutrally buoyant initially spherical elastic particles suspended in Newtonian and shear-thinning viscoelastic matrices subjected to pressure-driven flow in a cylindrical microchannel. Due to the well-known focusing mechanism induced by both particle deformability and fluid elasticity, the two particles are assumed to flow at the axis of the tube. The rheological behavior of the viscoelastic continuous phase is modeled via the Giesekus constitutive equation, whereas the particles are assumed to behave as neo-Hookean solids. The problem is tackled by employing a mixed finite-element method. The effects of particle deformability, fluid elasticity, confinement ratio, and initial interparticle separation distance on the pair dynamics are investigated. The main outcome of this study is a quantitative indication of the flow conditions and spatial configurations (initial distances) under which the particles will spontaneously form organized structures. Such results are helpful to design efficient microfluidic devices with the aim of promoting particle ordering. [ABSTRACT FROM AUTHOR]

Medical planning for space exploration is based on the "floating" blood bank model to store life-saving red blood cells (RBCs) for emergencies. The "floating" blood bank approach is not sufficient in cases where multiple crewmembers are affected by space anemia. In these situations, long-term preserved RBCs will be vital to guarantee the health and safety of crew members. Transfusable RBC units can only be refrigerated for 42 days or frozen at −80 °C. However, storing frozen RBCs at −80 °C is challenging during the confined condition of long-duration space flight. Freeze-dried, viable RBCs would be an appropriate alternative because they can be stored without cooling, are predicted to have a shelf-life of years, and could be transfused immediately after rehydration. This study explores if freeze-dried RBCs can be rehydrated and transfused in reduced gravity with similar outcomes in recovery as observed at Earth gravity. Experiments analyzing freeze-dried RBC recoveries, rehydration fluid dynamics, and transfusion flow rates were analyzed utilizing an experimental glovebox in simulated 0 g during parabolic flights. RBC recoveries and rehydration fluid dynamics for volumes of 5 mL and 10 mL were the same in simulated 0 g compared to results obtained at 1 g. A clinically acceptable range of flow rates for slow intravenous infusion and rapid fluid resuscitation was possible with the simple augmentation of a hand-pumped clinical pressure bag around a unit of rehydrated RBCs. The results demonstrate the potential feasibility of using freeze-dried cells for healthcare during deep-space exploration. • Rehydration of freeze-dried biologicals is feasible during simulated reduced gravity. • Freeze-dried red blood cells recovered in microgravity remain morphologically intact. • A syringe-based rehydration system minimized changes in fluid dynamics in reduced gravity. • Pressure sleeves generate clinically acceptable ranges of flow rates for transfusions in 0 g. [ABSTRACT FROM AUTHOR]

Human activity changes multiple factors in the environment, which can have positive or negative synergistic effects on organisms. However, few studies have explored the causal effects of multiple anthropogenic factors, such as urbanization and invasive species, on animals and the mechanisms that mediate these interactions. This study examines the influence of urbanization on the detrimental effect of invasive avian vampire flies (Philornis downsi) on endemic Darwin's finches in the Galápagos Islands. We experimentally manipulated nest fly abundance in urban and non‐urban locations and then characterized nestling health, fledging success, diet, and gene expression patterns related to host defense. Fledging success of non‐parasitized nestlings from urban (79%) and non‐urban (75%) nests did not differ significantly. However, parasitized, non‐urban nestlings lost more blood, and fewer nestlings survived (8%) compared to urban nestlings (50%). Stable isotopic values (δ15N) from urban nestling feces were higher than those from non‐urban nestlings, suggesting that urban nestlings are consuming more protein. δ15N values correlated negatively with parasite abundance, which suggests that diet might influence host defenses (e.g., tolerance and resistance). Parasitized, urban nestlings differentially expressed genes within pathways associated with red blood cell production (tolerance) and pro‐inflammatory response (innate immunological resistance), compared to parasitized, non‐urban nestlings. In contrast, parasitized non‐urban nestlings differentially expressed genes within pathways associated with immunoglobulin production (adaptive immunological resistance). Our results suggest that urban nestlings are investing more in pro‐inflammatory responses to resist parasites but also recovering more blood cells to tolerate blood loss. Although non‐urban nestlings are mounting an adaptive immune response, it is likely a last effort by the immune system rather than an effective defense against avian vampire flies since few nestlings survived. [ABSTRACT FROM AUTHOR]

High temperature and humidity affect the tribological performance of nitrile butadiene rubber (NBR) seals, which affects the precise positioning of cylinder systems. Therefore, it is crucial to study the effect of hydrothermal aging on the tribological performance of the NBR seals. In this study, the changes in the tribological performance of the NBR seals under hydrothermal aging conditions were investigated. The results show that the volatilization of additives and the increase in crosslink density of the NBR seals occurs in the hydrothermal aging environment, leading to the deterioration of their surface quality, elastic deformability, and tribological performance. The formation of surface micropores due to additive volatilization is the main factor in the degradation of tribological performance. [ABSTRACT FROM AUTHOR]

Sickle cell disease causes the deformation of erythrocytes into sickle cells. The study of this process using digital images of peripheral blood smears can help specialists to quantify the number of deformed cells in order to gauge the severity of the illness. A new method for classifying red blood cells into three categories: healthy, sickle cell disease, and other deformations is proposed. This method does not require obtaining the contour of each cell but instead utilizes information obtained from a small number of points, obtained through appropriate geometric sampling and the use of stereological formulas. The parameters utilized for classification are the bending energy times length (E) and the circular shape factor (F). In normal cells, which exhibit an almost circular shape, these parameters typically have values close to (1,1). To assess the effectiveness of classification using the parameters (E,F), a synthetic curve dataset and a dataset of red blood cells are employed, applying various supervised and unsupervised classification methods. [ABSTRACT FROM AUTHOR]

Mutations of the bridge-like lipid transport protein VPS13A and the lipid scramblase XK result in Chorea Acanthocytosis (ChAc) and McLeod syndrome (MLS), respectively, two similar conditions involving neurodegeneration and deformed erythrocytes (acanthocytes). VPS13A binds XK, suggesting a model in which VPS13A forms a lipid transport bridge between the endoplasmic reticulum (ER) and the plasma membrane (PM), where XK resides. However, studies of VPS13A in HeLa and COS7 cells showed that this protein localizes primarily at contacts of the ER with mitochondria. Overexpression of XK in these cells redistributed VPS13A to the biosynthetic XK pool in the ER but not to PM-localized XK. Colocalization of VPS13A with XK at the PM was only observed if overexpressed XK harbored mutations that disengaged its VPS13A-binding site from an intramolecular interaction. As the acanthocytosis phenotype of ChAc and MLS suggests a role of the two proteins in cells of the erythroid lineage, we explored their localization in K562 cells, which differentiate into erythroblasts upon hemin addition. When tagged VPS13A was overexpressed in hemin-treated K562 cells, robust formation of ER–PM contacts positive for VPS13A was observed and their formation was abolished in XK KO cells. ER–PM contacts positive for VPS13A were seldom observed in undifferentiated K562 cells, despite the presence of XK in these cells at concentrations similar to those observed after differentiation. These findings reveal that the interaction of VPS13A with XK at ER–PM contacts requires a permissive state which depends upon cell type and/or functional state of the cell. [ABSTRACT FROM AUTHOR]

The hematological effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important in COVID-19 pathophysiology. However, the interactions of SARS-CoV-2 with platelets and red blood cells are still poorly understood. There are conflicting data regarding the mechanisms and significance of these interactions. The aim of this review is to put together available data and discuss hypotheses, the known and suspected effects of the virus on these blood cells, their pathophysiological and diagnostic significance, and the potential role of platelets and red blood cells in the virus's transport, propagation, and clearance by the immune system. We pay particular attention to the mutual activation of platelets, the immune system, the endothelium, and blood coagulation and how this changes with the evolution of SARS-CoV-2. There is now convincing evidence that platelets, along with platelet and erythroid precursors (but not mature erythrocytes), are frequently infected by SARS-CoV-2 and functionally changed. The mechanisms of infection of these cells and their role are not yet entirely clear. Still, the changes in platelets and red blood cells in COVID-19 are significantly associated with disease severity and are likely to have prognostic and pathophysiological significance in the development of thrombotic and pulmonary complications. [ABSTRACT FROM AUTHOR]

A critical step in how malaria parasites invade red blood cells (RBCs) is the wrapping of the membrane around the egg-shaped merozoites. Recent experiments have revealed that RBCs can be protected from malaria invasion by high membrane tension. While cellular and biochemical aspects of parasite actomyosin motor forces during the malaria invasion have been well studied, the important role of the biophysical forces induced by the RBC membrane-cytoskeleton composite has not yet been fully understood. In this study, we use a theoretical model for lipid bilayer mechanics, cytoskeleton deformation, and membrane-merozoite interactions to systematically investigate the influence of effective RBC membrane tension, which includes contributions from the lipid bilayer tension, spontaneous tension, interfacial tension, and the resistance of cytoskeleton against shear deformation on the progression of membrane wrapping during the process of malaria invasion. Our model reveals that this effective membrane tension creates a wrapping energy barrier for a complete merozoite entry. We calculate the tension threshold required to impede the malaria invasion. We find that the tension threshold is a nonmonotonic function of spontaneous tension and undergoes a sharp transition from large to small values as the magnitude of interfacial tension increases. We also predict that the physical properties of the RBC cytoskeleton layer—particularly the resting length of the cytoskeleton—play key roles in specifying the degree of the membrane wrapping. We also found that the shear energy of cytoskeleton deformation diverges at the full wrapping state, suggesting the local disassembly of the cytoskeleton is required to complete the merozoite entry. Additionally, using our theoretical framework, we predict the landscape of myosin-mediated forces and the physical properties of the RBC membrane in regulating successful malaria invasion. Our findings on the crucial role of RBC membrane tension in inhibiting malaria invasion can have implications for developing novel antimalarial therapeutic or vaccine-based strategies. Author summary: RBC membrane tension plays an important role in regulating RBC shape and functionality. In particular, recent experimental studies have shown that elevated RBC membrane tension protects against severe malaria infection. In this study, we sought to identify how different contributions to the effective membrane tension can contribute to this mechanically driven protection against malaria invasion. Using a mathematical model, we derived a relationship between the effective tension of the RBC membrane—comprising a lipid bilayer and a cytoskeleton layer– and the degree of membrane wrapping during malaria invasion. Our model shows that the shear resistance of the RBC cytoskeleton plays an important role in inhibiting malaria invasion. Our findings can be generalized to the role of cell membrane mechanics in many wrapping phenomena providing insight into the crucial contributions of the host-cell membrane in protection against severe infections. [ABSTRACT FROM AUTHOR]

The proper regeneration of vessel anastomoses in microvascular surgery is crucial for surgical safety. Pituitary adenylate cyclase-activating polypeptide (PACAP) can aid healing by decreasing inflammation, apoptosis and oxidative stress. In addition to hematological and hemorheological tests, we examined the biomechanical and histological features of vascular anastomoses with or without PACAP addition and/or using a hemostatic sponge (HS). End-to-end anastomoses were established on the right femoral arteries of rats. On the 21st postoperative day, femoral arteries were surgically removed for evaluation of tensile strength and for histological and molecular biological examination. Effects of PACAP were also investigated in tissue culture in vitro to avoid the effects of PACAP degrading enzymes. Surgical trauma and PACAP absorption altered laboratory parameters; most notably, the erythrocyte deformability decreased. Arterial wall thickness showed a reduction in the presence of HS, which was compensated by PACAP in both the tunica media and adventitia in vivo. The administration of PACAP elevated these parameters in vitro. In conclusion, the application of the neuropeptide augmented elastin expression while HS reduced it, but no significant alterations were detected in collagen type I expression. Elasticity and tensile strength increased in the PACAP group, while it decreased in the HS decreased. Their combined use was beneficial for vascular regeneration. [ABSTRACT FROM AUTHOR]

Epigenetic modifications, particularly DNA methylation, have emerged as regulators of gene expression and are implicated in various biological processes and disease states. Understanding the factors influencing the epigenome is essential for unraveling its complexity. In this study, we aimed to identify how the methylome of buccal epithelial cells, a noninvasive and easily accessible tissue, is associated with demographic and health-related variables commonly used in clinical settings, such as age, sex, blood immune composition, hemoglobin levels, and others. We developed a model to assess the association of multiple factors with the human methylome and identify the genomic loci significantly impacted by each trait. We demonstrated that DNA methylation variation is accurately modeled by several factors. We confirmed the well-known impact of age and sex and unveiled novel clinical factors associated with DNA methylation, such as blood neutrophils, hemoglobin, red blood cell distribution width, highdensity lipoprotein cholesterol, and urea. Genomic regions significantly associated with these traits were enriched in relevant transcription factors, drugs, and diseases. Among our findings, we showed that neutrophil-impacted loci were involved in neutrophil functionality and maturation. Similarly, hemoglobin-influenced sites were associated with several diseases, including aplastic anemia, and the genomic loci affected by urea were related to congenital anomalies of the kidney and urinary tract. Our findings contribute to a better understanding of the human methylome plasticity and provide insights into novel factors shaping DNA methylation patterns, highlighting their potential clinical implications as biomarkers and the importance of considering these physiological traits in future medical epigenomic investigations. NEW & NOTEWORTHY We have developed a quantitative model to assess how the human methylome is associated with several factors and to identify the genomic loci significantly impacted by each trait. We reported novel health-related factors driving DNA methylation patterns and new site-specific regulations that further elucidate methylome dynamics. Our study contributes to a better understanding of the plasticity of the human methylome and unveils novel physiological traits with a potential role in future medical epigenomic investigations. [ABSTRACT FROM AUTHOR]

Nitrate poisoning due to the consumption of cabbages was diagnosed in a small goat flock, in Qena city, Egypt. The methylene blue 1% antidote (1 mg/kg BW) was given intravenously to the poisoned goats. Nitrate poisoning was confirmed in blood plasma, saliva, urine, and cabbage dry matter samples. The dark brown blood and methemoglobin fraction were 47.25 ± 0.58%. Green cabbage containing 7.1% nitrate on dried materials was fed to the goats. The nitrate concentration in the saliva was (59.50 ± 4.67), compared to the healthy goats reared in the same area and tested positive in the plasma and urine of intoxicated goats. Intoxication induced a significant decline in the Red Blood Cells count, hemoglobin concentration, and HCT % (P < 0.001), while the WBC count (P < 0.001), neutrophils (P < 0.001), and monocyte percentage were elevated (P < 0.002) in intoxicated goats, while the lymphocyte % (P < 0.01) significantly decreased when compared to the control. For the oxidative stress in the red blood cells, nitrate toxicity caused a significant elevation in the concentration of Malondialdehyde, (P < 0.001) while Superoxide Dismutase, Glutathione, and Glutathione S-Transferase levels were significantly reduced (P < 0.001) compared to the control. In this current report, the ingestion of goat to cabbage containing a high level of nitrate exhibited nitrate-nitrite intoxication. [ABSTRACT FROM AUTHOR]

Gravitational waves from compact binary coalescences are valuable for testing theories of gravity in the strong field regime. By measuring neutron star tidal deformability using gravitational waves from binary neutron stars, stringent constraints were placed on the equation of state of matter at extreme densities. Tidal Love numbers in alternative theories of gravity may differ significantly from their general relativistic counterparts. Understanding exactly how the tidal Love numbers change will enable scientists to untangle physics beyond general relativity from the uncertainty in the equation of state measurement. In this work, we explicitly calculate the fully relativistic l ≥ 2 tidal Love numbers for neutron stars in scalar-tensor theories of gravitation. We use several realistic equations of state to explore how the mass, radius, and tidal deformability relations differ from those of general relativity. We find that tidal Love numbers and tidal deformabilities can differ significantly from those in general relativity in certain regimes. The electric tidal deformability can differ by ∼200%, and the magnetic tidal deformability differs by ∼300%. These deviations occur at large compactnesses (C = M / r ≳ 0.2) and vary slightly depending on the equation of state. This difference suggests that using the tidal Love numbers from general relativity could lead to significant errors in tests of general relativity using the gravitational waves from binary neutron star and neutron star black hole mergers. [ABSTRACT FROM AUTHOR]

The periparturient period in small ruminants is considered crucial due to major endocrine, metabolic, and behavioral changes. These physiological variations can affect the normal hematological values of the animal, as well as the number and morphology of erythrocytes. The aim of this study was to determine the different morphological changes of erythrocytes that can occur in ewes during late pregnancy and their influence on erythrocytic index values. Our experimental study included 100 Rembi ewes during late pregnancy that were apparently healthy. Blood samples were collected in an EDTA tube for each studied subject for hematological analysis and blood smear preparation. Nine distinct erythrocyte morphological anomalies were found in our data. The most frequent anomalies were anemia, acanthocytes, and hemoglobin crystallization, with prevalence rates of 17%, 16%, and 15%, respectively. We recorded 12% of ewes with Heinz bodies and 4% with blood parasites and anemia. Besides, the erythrocyte shape of 22% of the study subjects remained unchanged. Red blood cells (RBCs) and hematocrit (Ht) values in anemic ewes with blood parasites were significantly (P 0.05) lower than those with no alterations in erythrocyte morphology. In contrast, a non-significant difference in hemoglobin (Hb) and mean corpuscular hemoglobin concentration (MCHC) values was seen in our results in response to changes in erythrocyte morphology. Hence, the end of pregnancy in prolific ewes affects the hematological profile causing different changes in erythrocyte morphology. These changes can be used as a reliable tool to assess ewes' health status during this period. [ABSTRACT FROM AUTHOR]

The dissemination of cancer cells is one of the main reasons for treatment failure. During the process of establishing distant metastases, cancer cells must migrate through narrow environments, such as intercellular junctions, extracellular matrix, and basement membranes. The deformability of the cell nucleus is a limiting factor for migration through narrow environments; therefore, as the largest and hardest organelle, the nucleus is a key factor in crossing restrictive spaces. Nesprin-1/2 provides mechanical linkage between the nucleus and the cytoskeleton, but the specific mechanism by Nesprin-1/2 regulating tumor cell nuclear deformation is unclear. Our study found that knocking down Nesprin-1/2 significantly weakens cell migration ability, and knocking down Nesprin-1/2 makes the nucleus becoming more easily deformed. Meanwhile, the knockdown of Nesprin-1/2 leads to a decrease in Lamin A/C levels. To explore whether Lamin A/C protein undergoes degradation, we treated cells with caspase-6 inhibitor Z-VEID-FMK, autophagy inhibitor 3-methyladenine (3-MA), or broad-spectrum proteasome inhibitor MG132, and found that knockdown of Nesprin-1/2 led to the degradation of Lamin A/C via the proteasome pathway. Through immunofluorescence experiments, we observed F-actin distribution in the process of pore migration, and found that knockdown of Nesprin-1/2 weakened the pushing force of the nuclear tail, making it unable to propel the nucleus forward. In conclusion, this study demonstrates that Nesprin-1/2 regulates nuclear deformation and reorganizes the cytoskeleton, which together affects cell pore migration and provides a theoretical reference for the study of nuclear deformation mechanisms. [ABSTRACT FROM AUTHOR]

The effects of endothelin-1 (ET-1) on erythrocytes from sickle cell disease (SCD) patients have been described, but mechanisms of ET-1 regarding primary erythrocyte functions remain unknown. ET-1 is a vasoconstrictor peptide produced by endothelial cells, and the expression of ET-1 is increased in SCD. The present study used ex vivo experiments with sickle cell erythrocytes, ET-1, and bosentan, a dual antagonist of ETA and ETB receptors. We performed a hemoglobin S (HbS) polymerization assay with three concentrations of ET-1 (1, 20, and 50 pg/mL) and bosentan (100 nmol/L). ET-1 increased HbS polymerization at all concentrations, and this effect was suppressed by bosentan. For the deformability assay, red blood cells (RBCs) were incubated on a Sephacryl column with the same concentrations of ET-1 and bosentan. ET-1 decreased deformability, and this effect was reversed by bosentan. To observe erythrocyte adhesion, ET-1 and bosentan were incubated with RBCs in thrombospondin-coated 96-well plate, which demonstrated that ET-1 decreased adhesion but that bosentan enhanced adhesion. We also assessed erythrocyte apoptosis and observed decreased eryptosis induced by ET-1, and these effects were inhibited bosentan. Thus, these findings demonstrated that ET-1 modulates HbS polymerization, erythrocyte deformability, adhesion to thrombospondin, and eryptosis, and these effects were suppressed or enhanced by bosentan. [ABSTRACT FROM AUTHOR]