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COVID-19 infection is associated with a variety of vascular occlusive morbidities. However, a comprehensive understanding of how this virus can induce vascular complications remains lacking. Here, we show that a peptide fragment of SARS-CoV-2 spike protein, S192 (sequence 192-211), is capable of forming amyloid-like aggregates that can induce agglutination of red blood cells, which was not observed with low- and non-aggregated S192 peptide. We subsequently screened eight amyloid-binding molecules and identified BAM1-EG6, a benzothiazole amphiphile, as a promising candidate capable of binding to aggregated S192 and partially inhibiting its agglutination activity. These results provide new insight into a potential molecular mechanism for the capability of spike protein metabolites to contribute to COVID-19-related blood complications and suggest a new therapeutic approach for combating microvascular morbidities in COVID-19 patients.

It is important to understand the dynamics of red blood cells (RBCs) in blood flow. This requires the formulation of coarse-grained RBC models that reproduce the hydrodynamic properties of blood accurately. One of the models that successfully reproduces the rheology and morphology of blood has been proposed by Fedosov et al. [Comput. Methods Appl. Mech. Eng. 199, 1937–1948 (2010)]. The proposed RBC model contains several parameters whose values are determined by either various experiments or physical requirements. In this study, we developed a new method of determining parameter values precisely from the fluctuations of the RBC membrane. Specifically, we studied the relationship between the spectra of the fluctuations and model parameters. Characteristic peaks were observed in the spectra, whose peak frequencies were dependent on the parameter values. In addition, we investigated the spectra of the radius of gyration. We identified the peaks originating from the spring potential and the volume-conserving potential appearing in the spectra. These results lead to the precise experimental determination of the parameters used in the RBC model. [ABSTRACT FROM AUTHOR]

This study aims to investigate the effects of hypoxically stored Red Blood Cells (RBCs) in a rat model of traumatic brain injury followed by severe hemorrhagic shock (HS) and resuscitation. RBCs were made hypoxic using an O2 depletion system (Hemanext Inc. Lexington, MA) and stored for 3 weeks. Experimental animals underwent craniotomy and blunt brain injury followed by severe HS. Rats were resuscitated with either fresh RBCs (FRBCs), 3-week-old hypoxically stored RBCs (HRBCs), or 3-week-old conventionally stored RBCs (CRBCs). Resuscitation was provided via RBCs transfusion equivalent to 70 % of the shed blood and animals were followed for 2 h. The control group was comprised of healthy animals that were not instrumented or injured. Post-resuscitation hemodynamics and lactate levels were improved with FRBCs and HRBCs, and markers of organ injury in the liver (Aspartate aminotransferase [AST]), lung (chemokine ligand 1 [CXCL-1] and Leukocytes count), and heart (cardiac troponin, Interleukin- 6 [IL-6] and Tumor Necrosis Factor Alpha[TNF-α]) were lower with FRBCs and HRBCs resuscitation compared to CRBCs. Following reperfusion, biomarkers for oxidative stress, lipid peroxidation, and RNA/DNA injury were assessed. Superoxide dismutase [SOD] levels in the HRBCs group were similar to the FRBCs group and levels in both groups were significantly higher than CRBCs. Catalase levels were not different than control values in the FRBCs and HRBCs groups but significantly lower with CRBCs. Thiobarbituric acid reactive substances [Tbars] levels were higher for both CRBCs and HRBCs. Hypoxically stored RBCs show few differences from fresh RBCs in resuscitation from TBI + HS and decreased organ injury and oxidative stress compared to conventionally stored RBCs.

Red blood cell (RBC) metabolic reprogramming upon exposure to high altitude contributes to physiological human adaptations to hypoxia, a multifaceted process critical to health and disease. To delve into the molecular underpinnings of this phenomenon, first, we performed a multi-omics analysis of RBCs from six lowlanders after exposure to high-altitude hypoxia, with longitudinal sampling at baseline, upon ascent to 5,100 m and descent to sea level. Results highlighted an association between erythrocyte levels of 2,3-bisphosphoglycerate (BPG), an allosteric regulator of hemoglobin that favors oxygen off-loading in the face of hypoxia, and expression levels of the Rhesus blood group RHCE protein. We then expanded on these findings by measuring BPG in RBCs from 13,091 blood donors from the Recipient Epidemiology and Donor Evaluation Study. These data informed a genome-wide association study using BPG levels as a quantitative trait, which identified genetic polymorphisms in the region coding for the Rhesus blood group RHCE as critical determinants of BPG levels in erythrocytes from healthy human volunteers. Mechanistically, we suggest that the Rh group complex, which participates in the exchange of ammonium with the extracellular compartment, may contribute to intracellular alkalinization, thus favoring BPG mutase activity.

BACKGROUND: Mechanical thrombectomy (MT) has become the gold standard care for treating acute ischemic stroke (AIS) due to large vessel occlusion. Emerging evidence suggests that understanding the composition of clots prior to intervention could be useful for the selection of neuroendovascular techniques, potentially improving the efficacy of treatments. However, current imaging modalities lack the ability to distinguish clot composition accurately and reliably. Since water content can influence signal intensity on CT and MRI scans, its assessment may provide indirect clues about clot composition. This study aimed to elucidate the correlation between water content and clot composition using human clots retrieved from stroke patients and experimentally generated ovine clots. MATERIALS AND METHODS: This study involved an analysis of ten clots retrieved from patients with AIS undergoing MT. Additionally, we created ten red blood cells (RBC)-rich and ten fibrin-rich ovine blood clots, which were placed in a human intracranial vascular model under realistic flow conditions. The water content and compositions of these clots were evaluated, and linear regression analyses were performed to determine the relationship between clot composition and water content. RESULTS: The regression analysis in human stroke clots revealed a significant negative association between RBC concentration and water content. We also observed a positive correlation between water content and both fibrin and platelets in ovine blood clots. Conclusion.

Spleen marginal zone (MZ) B cells are important for antibody responses against blood-borne antigens. The signals they use to detect exposure to blood are not well defined. Here, using intravital two-photon microscopy in mice, we observe transient contacts between MZ B cells and red blood cells that are in flow. We show that MZ B cells use adhesion G-protein-coupled receptor ADGRE5 (CD97) for retention in the spleen. CD97 function in MZ B cells depends on its ability to undergo autoproteolytic cleavage and signaling via Gα13 and ARHGEF1. Red blood cell expression of the CD97 ligand CD55 is required for MZ B cell homeostasis. Applying a pulling force on CD97-transfected cells using an optical C-trap and CD55+ beads leads to accumulation of active RhoA and membrane retraction. Finally, we show that CD97 deficiency leads to a reduced T cell-independent IgM response. Thus, our studies provide evidence that MZ B cells use mechanosensing to position in a manner that enhances antibody responses against blood-borne antigens.

Introduction Battlefield trauma necessitates prompt hemostatic intervention to mitigate fatalities resulting from critical blood loss. Insights from Operation Enduring Freedom and Operation Iraqi Freedom emphasize the limitations of conventional methods, such as tourniquets, especially in noncompressible torso hemorrhage. Despite advancements in hemostatic agents, the evolving dynamics of multidomain operations necessitate novel, lightweight strategies for hemorrhage control. This study investigates the Silicone-Based Polymer (SBP) Universal Combat Matrix (UCM) by SiOxMed, a multimodal matrix exhibiting efficacy in lethal hemorrhage models. The study evaluates UCM's multiday hemostatic capabilities in a noncompressible torso hemorrhage model, offering pivotal insights for potential deployment in battlefield trauma. Materials and Methods This research was performed under Institutional Animal Care and Use Committee approval and was designed to replicate austere conditions in an off-site enclosed facility. Yorkshire Hampshire swine underwent baseline assessments and anesthesia induction (n  = 3). A Grade IV liver injury was made by incising X-shaped lesions, each measuring 4 cm × 2.5 cm, into the diaphragmatic surface of the left and right middle lobes using a scalpel blade, resulting in a lesion region of approximately 3 cm × 6 cm × 3 cm, followed by 30 seconds of uncontrolled bleeding. The injuries were then treated with SBP. Intensive care unit monitoring for 1 hour ensured sustained hemostasis, followed by 48 hours of postanesthesia monitoring and then a return to the operating table to visualize sustained hemostasis. Posteuthanasia, liver tissue underwent histological assessments to evaluate the hemorrhagic interface and liver tissue reactivity. Results The average time to hemostatic control was 247.3 ± 71.3 seconds. Stable heart rate (81.3 ± 10.0) and respiratory rate (31.7 ± 16.5) were maintained during intensive care unit monitoring. All swine survived the 1-hour anesthesia monitoring period and the subsequent 48-hour monitoring (average survival time, 48.0 hours ± 0.0, n  = 3). Visualization of the abdominal cavity at 48 hours revealed no hemorrhage. Histological assessment demonstrated aligned red blood cells and stratified layers of fibrin at the hemorrhagic interface. Masson's Trichrome analysis demonstrated a reactive and regenerative scenario 48 hours postinjury, with a collagen membrane demarcating uninjured and exposed liver regions, along with a comprehensive stromal response. Conclusions In conclusion, our investigation into the SBP UCM hemostatic efficacy in a grade IV liver laceration model demonstrates its rapid and reliable action in controlling bleeding, showcasing practicality with an average mass of 4.0 ± 1.0 g. Silicone-Based Polymer sustained hemostasis without adverse physiological effects, as evidenced by stable parameters and the survival of all swine during and after anesthesia. Macroscopic examination at 48 hours revealed durable adherence with no indications of hemorrhage. Histological evaluations highlighted SBP's role in stable clot formation, fibrinogenesis, and tissue regeneration, indicating its potential as a multimodal wound dressing. Although promising, the study has limitations, emphasizing the need for future research with larger samples and controls. This work sets the stage for exploring SBP's clinical implications, particularly in scenarios where lightweight, multimodal technologies are crucial for addressing traumatic injuries and enhancing military medical capabilities. [ABSTRACT FROM AUTHOR]

The hybrid of female white crucian carp (Carassius auratus cuvieri, WCC) × male red crucian carp (Carassius auratus red var. RCC) (WR), combines desirable characteristics of both parents, including tender meat, rapid growth rate, and strong resistance. To test the hypoxia tolerance of WR, an experiment of exposure to hypoxic conditions was conducted on WR, RCC, and WCC. The results showed that WR and RCC exhibited stronger hypoxia tolerance capacity compared to WCC. The strong resistance to hypoxia of WR and RCC was manifested by the absence of damage to the hepatopancreas after hypoxia, and the fish can adapt to the hypoxic environment by enhancing the hematopoietic function of hematopoietic tissue, remodeling gill morphology, and activating the antioxidant system. By contrast, after hypoxia, the number of red blood cells and the concentration of hemoglobin in the blood of WCC decreased, and the hepatopancreas was seriously damaged, indicating that the WCC is not as tolerant to low oxygen conditions as RCC and WR. [ABSTRACT FROM AUTHOR]

Several diseases like Sickle Cell Anemia, Thalassemia, Hereditary Spherocytosis, Malaria, and Micro-angiopathic Hemolytic Anemia can alter the normal shape of red blood cells (RBCs). The objective of this study is to gain insight into how a change in RBC deformability can affect blood heat transfer. The heat sink effect in a bifurcated vessel with two asymptotic cases (case 1: deformable and case 2: nondeformable RBCs) is being studied during hyperthermia treatment in a three-dimensional bifurcated vessel, whose wall is being subjected to constant heat flux boundary condition. Euler–Euler multiphase method along with the granular model and Kinetic theory is used to include the particle nature of RBCs during blood flow in the current model. To enhance the efficiency of the numerical model, user-defined functions (UDFs) are imported into the model from the C++ interface. The numerical model used is verified with the experimental results from (Carr and Tiruvaloor, 1989, “Enhancement of Heat Transfer in Red Cell Suspensions In Vitro Experiments,” ASME J. Biomech. Eng., 111(2), pp. 152–156; Yeleswarapu et al. 1998, “The Flow of Blood in Tubes: Theory and Experiment,” Mech. Res. Commun., 25(3), pp. 257–262). The results indicate that the deformability of RBCs can change both the flow dynamics and heat sink effect in a bifurcated vessel, which subsequently affects the efficacy and efficiency of the thermal ablation procedure. Both spatial and transient Nusselt numbers of blood flow with deformable RBCs are slightly higher compared to the one with nondeformable RBCs. [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. A dysregulated inflammatory response contributes to the occurrence of disorders in cows during the transition period from pregnancy to lactation. However, a detailed characterization of clinically healthy cows that exhibit an enhanced inflammatory response during this critical period remains incomplete. In this experiment, a total of 99 individual transition dairy cows and 109 observations (18 cows monitored in 2 consecutive lactations), submitted to similar transition management were involved to evaluate the relationship between elevated an inflammatory response and metabolic and oxidative status, as well as transition outcomes. Blood was taken at −7, 3, 6, 9, and 21 DIM, and concentrations of metabolic parameters (glucose, β-hydroxybutyric acid, nonesterified fatty acids [NEFA], insulin, IGF-1, and fructosamine) were analyzed. Additionally, oxidative parameters (proportion of oxidized glutathione to total glutathione in red blood cells, the activity of glutathione peroxidase [GPx] and superoxide dismutase, concentrations of malondialdehyde, and oxygen radical absorbance capacity) and acute phase proteins (APP) including haptoglobin (Hp), serum amyloid A (SAA) and albumin-to-globulin ratio (A:G) were determined in the blood at 21 DIM. The 3 APP parameters were used to group clinically healthy cows into 2 categories through k -medoids clustering (i.e., a group showing an acute phase response, APR; n = 39) and a group not showing such a response (i.e., non-APR; n = 50). Diseased cases (n = 20) were handled in a separate group. Lower SAA and Hp concentrations as well as higher A:G were observed in the non-APR group, although for Hp, differences were observed from the APR group and not from the diseased group. Only 1 of the 5 oxidative parameters differed between the groups, with the non-APR group exhibiting lower GPx activity compared with the diseased group. The non-APR group showed the highest IGF-1 levels among the 3 groups and and lower NEFA concentrations compared with the diseased groups. Cows in the diseased group also showed reduced dry matter intake and milk yield compared with clinically healthy cows, regardless of their inflammatory status. Moreover, the APR group exhibited temporarily lower activity levels compared with the non-APR group. These findings highlight that cows with a lower inflammatory status after 21 DIM exhibited better metabolic health characteristics and productive performance, as well as activity levels. Nevertheless, the detrimental effects of a higher inflammatory status in the absence of clinical symptoms are still relatively limited. [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. In countries with pasture-based dairy systems and relatively cold winters, such as New Zealand, it is common to manage pregnant, nonlactating cows on forage crop paddocks rather than pasture, due to slow pasture growth rates. Wintering dairy cattle on grazed crops can compromise welfare if wet and muddy underfoot conditions occur, which can reduce lying. This study investigated behavioral and physiological indicators of welfare of cows under 2 wintering practices: cows managed on and grazed kale crop (Brassica oleracea), and cows managed on pasture with baled hay. Following dry-off (d 0), 80 cows were randomly assigned to 1 of the 2 wintering practices (40 cows/practice) and monitored between d 4 and 32 (phase 1). During this period, lying and stepping behavior was continuously recorded using leg-based accelerometers. Blood samples were obtained at d 0 and 32 for measurements of thyroxine (T4), nonesterified fatty acids (NEFA), white blood cells (WBC), and red blood cells. All data for phase 1 were presented descriptively due to the lack of treatment replication. Daily mean air temperature during this period was 5.2°C (range: 0.0–10.7°C), and rainfall was 1.1 mm/d (range: 0–5.6mm/d). Between d 4 and 32, cows in both groups spent similar amounts of time lying (pasture with hay cows: 8.9 h/24 h ± 2.57, kale crop cows: 8.7 h/24 h ± 3.06, mean ± SEM). Both groups reduced their lying on wet and cold days, and there was evidence of rebound lying once unfavorable weather conditions stopped. Cows on kale crop had numerically higher NEFA and lower WBC compared with cows managed on pasture, although most physiological values were within normal ranges. In a second phase of the study (d 34 and 35), cows were managed under controlled, replicated conditions in the 2 wintering practices using typical on-farm stocking rates (2 or 4 cows per group in the pasture with hay and kale crop treatments, respectively; n = 10 groups/treatment). During this period, cow behavior, skin and surface temperatures, hygiene scores, feed intakes, and ground conditions were measured. Weather conditions during the 48-h exposure were mostly cold and dry (mean air temperature: 7.8°C, range: −2.2 to 20.5°C). Cows managed on pasture with hay spent more time lying down on the first day of exposure; however, this was likely due to less space being available to kale cows on this day. Cows managed on pasture with hay ruminated more than cows on kale crop on both days of observations (d 1: 37.9% vs. 30.9% of observations, d 2: 36.8% vs. 28.7% of observations for pasture with hay and kale crop groups, respectively) and were lying more often in postures indicative of greater thermal comfort. Cows managed on pasture with hay had higher skin and surface temperatures compared with cows on kale crop, whereas cows on kale crop had dirtier coats. Results suggest that opportunities for thermal comfort were greater for cows managed on pasture with hay bales, which may be due to increased rumination activities and more insulated lying areas. [ABSTRACT FROM AUTHOR]

Background: Intracellular methotrexate polyglutamates (MTX‐PGs) concentrations are measurable in red blood cells (RBCs) during MTX treatment. MTX‐PG3 concentrations correlate with efficacy in patients with Crohn's disease (CD). Since RBCs are not involved in pathogenesis of CD and lack extended MTX metabolism, we determined MTX‐PGs accumulation in peripheral blood mononuclear cells (PBMCs: effector cells) and intestinal mucosa (target cells) and compared those with RBCs as a potential more precise biomarker. Methods: In a multicentre prospective cohort study, blood samples of patients with CD were collected during the first year of MTX therapy. Mucosal biopsies were obtained from non‐inflamed rectum and/or inflamed intestine. MTX‐PGs concentrations in mucosa, PBMCs and RBCs were measured by liquid chromatography–tandem mass spectrometry. Results: From 80 patients with CD, a total of 27 mucosal biopsies, 9 PBMC and 212 RBC samples were collected. From 12 weeks of MTX therapy onwards, MTX‐PG3 was the most predominant species (33%) in RBCs. In PBMCs, the distribution was skewed towards MTX‐PG1 (48%), which accounted for an 18 times higher concentration than in RBCs. Long‐chain MTX‐PGs were highly present in mucosa: 21% of MTX‐PGtotal was MTX‐PG5. MTX‐PG6 was measurable in all biopsies. Conclusions: MTX‐PG patterns differ between mucosa, PBMCs and RBCs of patients with CD. [ABSTRACT FROM AUTHOR]

Background: High mechanical shear stress (HMSS) generated by blood pumps during mechanical circulatory support induces blood damage (or function alteration) not only of blood cell components but also of plasma proteins. Methods: In the present study, fresh, healthy human blood was used to prime a blood circuit assisted by a CentriMag centrifugal pump at a flow rate of 4.5 L/min under three pump pressure heads (75, 150, and 350 mm Hg) for 4 h. Blood samples were collected for analyses of plasma‐free hemoglobin (PFH), von Willebrand factor (VWF) degradation and platelet glycoprotein (GP) IIb/IIIa receptor shedding. Results: The extent of all investigated aspects of blood damage increased with increasing cross‐pump pressure and duration. Loss of high‐molecular‐weight multimers (HMWM)‐VWF in Loop 2 and Loop 3 significantly increased after 2 h. PFH, loss of HMWM‐VWF, and platelet GPIIb/IIIa receptor shedding showed a good linear correlation with mean shear stress corresponding to the three pump pressure heads. Conclusions: HMSS could damage red blood cells, cause pathological VWF degradation, and induce platelet activation and platelet receptor shedding. Different blood components can be damaged to different degrees by HMSS; VWF and VWF‐enhanced platelet activation may be more susceptible to HMSS. [ABSTRACT FROM AUTHOR]

Hypertension (HT) is a common chronic disease that often causes target-organ damage and severe complications, contributing to cardiovascular morbidity and mortality worldwide. Accumulating evidence suggests that inflammation plays a prominent role in the initiation and progression of HT. Multiple inflammatory biomarkers have been proposed to predict HT. Several new hematological parameters can reflect the inflammatory response and platelet activation. The major advantage of hematological parameters over conventional inflammatory markers is that they are relatively inexpensive and easily obtained from routine blood tests. Numerous studies have investigated several hematological parameters for their utility as predictive biomarkers for the diagnosis and prognosis of HT. Among them, the neutrophil to lymphocyte ratio (NLR), monocyte to high density lipoprotein cholesterol ratio (MHR), red cell distribution width (RDW), platelet to lymphocyte ratio (PLR), mean platelet volume (MPV), platelet distribution width (PDW), and systemic immune-inflammation index (SII) have recently received attention. We searched PubMed and Embase databases (up to September 18, 2022) to assess the relationships between hematological parameters and HT. This review discusses the diagnostic and prognostic value of these hematological parameters in HT, providing an important basis for early screening, risk stratification, and optimal management of hypertensive patients. [ABSTRACT FROM AUTHOR]

Although transcatheter aortic valve replacement (TAVR) is safe and effective, mortality and bleeding events post procedure are important. The present study investigated the changes in hematologic parameters to evaluate whether they predict mortality or major bleeding. We enrolled 248 consecutive patients (44.8% male; mean age 79.0 ± 6.4 years) undergoing TAVR. In addition to demographic and clinical examination, blood parameters were recorded before TAVR, at discharge, 1 month and 1 year. Hemoglobin levels before TAVR 12.1 ± 1.8 g/dL, 10.8 ± 1.7 g/dL at discharge, 11.7 ± 1.7 g/dL at first month, 11.8 ± 1.4 g/dL at first year (Hemoglobin values compared with pre-TAVR, P <.001, P =.019, P =.047, respectively). Mean platelet volume (MPV) before TAVR 8.72 ± 1.71 fL, 8.16 ± 1.46 fL at discharge, 8.09 ± 1.44 fL at first month, 7.94 ± 1.18 fL at first year (MPV values compared with pre-TAVR, P <.001, P <.001, P <.001, respectively). Other hematologic parameters were also evaluated. Hemoglobin, platelet count, MPV, and red cell distribution width before the procedure, at discharge, and at the first year did not predict mortality and major bleeding in receiver operating characteristic analysis. After multivariate Cox regression analysis, hematologic parameters were not independent predictors of in-hospital mortality, major bleeding, and death at 1 year after TAVR. [ABSTRACT FROM AUTHOR]

Millions of people around the world have iron deficiency, which is one of several important nutritional disorders. Despite recent advances in the prevention and treatment of these deficiencies, it is estimated that over two billion individuals worldwide are at risk for vitamin A, iodine, and/or iron insufficiency. Many major health concerns can result from micronutrient deficits. Lack of iron, folate, B12, and A may cause anemia. Anemia causes weariness, weakness, breathlessness, and disorientation due to low red blood cell or hemoglobin levels. Biofortification, a way to make staple foods with more micronutrients, could help lower malnutrition. Plant growth-promoting rhizobacteria (PGPR) can boost the amount of iron in edible plant tissues by making it easier for iron to get to those tissues. A pot experiment was conducted at ISES, University of Agriculture, Faisalabad, to evaluate the impact of well-characterized rhizobacterial strains (Acinetobacter calcoaceticus and Bacillus simplex) alone and in combination with L-tryptophan (a plant growth regulator (PGR)) on agronomic, tuber, and nutritional attributes of potato. Results revealed that inoculation significantly enhanced the iron content of potato tubers compared to control plants. When rhizobacteria, L-tryptophan, and iron were added to the soil, the number of tubers grew by 68.24% compared to the control plants where neither PGPR nor PGR was applied. Biofortifying potatoes with microbes can help people get more micronutrients, especially in countries with few resources. These results showed that PGPR can help plants get more Fe from the soil if more Fe is added to the soil. These results provide support for the hypothesis that microbial aided biofortification in crops might reduce human micronutrient insufficiency, particularly in areas with little resources. [ABSTRACT FROM AUTHOR]

BACKGROUND: Oyster polypeptide (OP) is a mixture of oligopeptides extracted from oysters through enzyme lysis, separation, and purification. It is associated with immunomodulatory effects, but the underlying mechanisms are not known. This study therefore combined proton nuclear magnetic resonance (1H‐NMR) urinary metabolomics and 16S rRNA gene sequencing of the gut microbiome to determine the immunoprotective mechanisms of OP in rats subjected to cyclophosphamide‐induced immunosuppression. RESULTS: Oyster polypeptide restored the body weight and the structure of spleen and thymus in rats with cyclophosphamide‐induced immunosuppression. It upregulated the levels of white blood cells (WBCs), hemoglobin (HGB), platelets (PLT), red blood cells (RBCs), immunoglobulin G (IgG), immunoglobulin M (IgM), cytokines such as interleukin‑6 (IL‐6) and tumor necrosis factor‐α (TNF‐α), and increased the numbers of CD3+ and CD4+ T cells in the immunosuppressed rats. The 1H‐NMR metabolomics results showed that OP significantly reversed the levels of ten metabolites in urine, including 2‐oxoglutarate, citrate, dimethylamine, taurine, N‐phenylacetylglycine, alanine, betaine, creatinine, uracil, and benzoate. The 16S rRNA gene sequencing results showed that OP restored the gut microbiome homeostasis by increasing the abundance of beneficial bacteria and reducing the abundance of pathogenic bacteria. Finally, a combination of metabolomics and microbiomics found that the metabolism of taurine and hypotaurine, and the metabolism of alanine, aspartate, and glutamate were disturbed, but these metabolic pathways were restored by OP. CONCLUSION: This study demonstrated that OP had immunoprotective effects in rats with cyclophosphamide‐induced immunosuppression by restoring key metabolic pathways and the gut microbiome homeostasis. Our findings provide a framework for further research into the immunoregulatory mechanisms of OP and its potential use in drugs and nutritional supplements. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

The study aimed to evaluate the ameliorative potential of Nigella sativa oil (N.s) against the adverse effects induced by atrazine (ATZ) in mice. Four groups were divided into: Control group (untreated); N.s group (N. sativa oil, 2 mL/kg/BW); ATZ group (atrazine 200 mg/kg/BW); ATZ+N.s group (atrazine 200 mL/kg/BW; and N. sativa oil, 2 mL/kg/BW). All doses were administered by gavage once daily for 4 weeks. The atrazine-administered group showed a significant increase in total leukocytes, granulocytes, and agranulocytes and a decrease in red blood cells, hemoglobin, mean corpuscular volume, and packed cell volume. Serum concentrations of aspartate aminotransferase, alanine transaminase, and alkaline phosphatase were high in the ATZ group. Atrazine exposure reduced serum albumin and total protein levels in the blood. A significantly higher concentration of bilirubin, urea, and creatinine was also found in the ATZ group. The simultaneous administration of atrazine and N. sativa led to improvements in all the parameters studied above. Thus, this study revealed that atrazine exposure has toxic effects on hematological parameters, liver, and kidney function, and that N. sativa oil reduces these toxic effects of atrazine in male mice. [ABSTRACT FROM AUTHOR]

• A computational frame was proposed to predict diabetes that collected from hospitals and health center by leveraging blood routine data. • The contributions of different blood routine indicators for diabetes were identified by our frame. • A nomogram was constructed for assessing the influence of blood routine indicators on prediction outcomes. Diabetes stands as one of the most prevalent chronic diseases globally. The conventional methods for diagnosing diabetes are frequently overlooked until individuals manifest noticeable symptoms of the condition. This study aimed to address this gap by collecting comprehensive datasets, including 1000 instances of blood routine data from diabetes patients and an equivalent dataset from healthy individuals. To differentiate diabetes patients from their healthy counterparts, a computational framework was established, encompassing eXtreme Gradient Boosting (XGBoost), random forest, support vector machine, and elastic net algorithms. Notably, the XGBoost model emerged as the most effective, exhibiting superior predictive results with an area under the receiver operating characteristic curve (AUC) of 99.90% in the training set and 98.51% in the testing set. Moreover, the model showcased commendable performance during external validation, achieving an overall accuracy of 81.54%. The probability generated by the model serves as a risk score for diabetes susceptibility. Further interpretability was achieved through the utilization of the Shapley additive explanations (SHAP) algorithm, identifying pivotal indicators such as mean corpuscular hemoglobin concentration (MCHC), lymphocyte ratio (LY%), standard deviation of red blood cell distribution width (RDW-SD), and mean corpuscular hemoglobin (MCH). This enhances our understanding of the predictive mechanisms underlying diabetes. To facilitate the application in clinical and real-life settings, a nomogram was created based on the logistic regression algorithm, which can provide a preliminary assessment of the likelihood of an individual having diabetes. Overall, this research contributes valuable insights into the predictive modeling of diabetes, offering potential applications in clinical practice for more effective and timely diagnoses. [ABSTRACT FROM AUTHOR]

Red blood cells (RBCs) are the most abundant human blood cells. RBC aggregation and deformation strongly determine blood viscosity which impacts hemorheology and microcirculation. In turn, RBC properties depend on different endogenous and exogenous factors. One such factor is nitric oxide (NO), which is mainly produced by endothelial cells (EC) from L-arginine amino acid in the circulatory system. Since the mechanisms of the RBC-endothelium interplay are not clear up to date and considering its possible clinical importance, the aims of this study are to investigate in vitro: (1) The effect of L-arginine induced NO on RBC aggregation and adhesion to endothelium; (2) the NO effect on RBC aggregation and deformation induced by L-arginine and sodium nitroprusside without the presence of endothelium in the samples. The RBC aggregation and adhesion to a monolayer of EC were studied using optical tweezers (OT). The RBC deformability and aggregation without endothelium in the samples were studied using the flow chamber method and Myrenne aggregometer. We confirmed that NO increases deformability and decreases aggregation of RBCs. We showed that the soluble guanylate cyclase pathway appears to be the only NO signaling pathway involved. In the samples with the endothelium, the "bell-shaped" dependence of RBC aggregation force on L-arginine concentration was observed, which improves our knowledge about the process of NO production by endothelium. Additionally, data related to L-arginine accumulation by endothelium were obtained: Necessity of the presence of extracellular L-arginine stated by other authors was put under question. In our study, NO decreased the RBC-endothelium adhesion, however, the tendency appeared to be weak and was not confirmed in another set of experiments. To our knowledge, this is the first attempt to measure the forces of RBC adhesion to endothelium monolayer with OT. [ABSTRACT FROM AUTHOR]

In-vivo flow cytometry is a noninvasive real-time diagnostic technique that facilitates continuous monitoring of cells without perturbing their natural biological environment, which renders it a valuable tool for both scientific research and clinical applications. However, the conventional approach for improving classification accuracy often involves labeling cells with fluorescence, which can lead to potential phototoxicity. This study proposes a label-free in-vivo flow cytometry technique, called dynamic YOLOv4 (D-YOLOv4), which improves classification accuracy by integrating absorption intensity fluctuation modulation (AIFM) into YOLOv4 to demodulate the temporal features of moving red blood cells (RBCs) and platelets. Using zebrafish as an experimental model, the D-YOLOv4 method achieved average precisions (APs) of 0.90 for RBCs and 0.64 for thrombocytes (similar to platelets in mammals), resulting in an overall AP of 0.77. These scores notably surpass those attained by alternative network models, thereby demonstrating that the combination of physical models with neural networks provides an innovative approach toward developing label-free in-vivo flow cytometry, which holds promise for diverse in-vivo cell classification applications. [ABSTRACT FROM AUTHOR]

Red blood cell (RBC) aggregation as well as their deformation significantly affects blood microrheology. These processes depend on various factors, one of which is concentration of the nitric oxide, one of the main signaling molecule in the bloodstream. The purpose of this study was to investigate the effect of nitric oxide on the microrheological properties of red blood cells (RBCs) in RBC samples of various media after the addition of nitric oxide donor sodium nitroprusside in vitro. Microrheological properties were measured using laser aggregometer and ektacytometer based on diffuse light scattering and diffraction of laser light on a suspension of RBCs, respectively. The study found that heparin-stabilized blood showed increased RBC aggregation and deformation with sodium nitroprusside concentrations of 100, and 200 μ M, while EDTA-stabilized blood showed slightly decreased aggregation and unchanged deformation. With washed RBCs in dextran solution, the addition of sodium nitroprusside (in the concentrations of 100, and 200 μ M) resulted in decreased aggregation and increased deformation. These findings aid in our understanding of nitric oxide's effect on RBC microrheological properties. [ABSTRACT FROM AUTHOR]

The aim of this work is to investigate the entropy generation and thermal characteristics of couple stress blood nanofluid on the peristaltic flow of gold nanoparticles being conveyed through an asymmetric channel through a porous medium. The distinctive characteristics of the nanoparticles such as their inspiring thermal conductivity make them a vital aspect of contemporary heat exchangers and nanotechnology. To create contrast-enhanced tracers intended for dynamic X-ray imaging of blood flows, gold nanoparticles have been incorporated into human red blood cells. The possibility for dynamic imaging with X-rays of blood flows provided by red blood cells in combination with gold nanoparticles has the potential to be advantageous for clinical applications. The main investigation focuses on the current situation of peristaltic motion with gyrotactic microorganisms in which the effects of Brownian motin, thermophoresis, thermal radiations, convective boundary conditions, wall slip, magnetic field, viscous dissipation and Joule heating are present. Lubrication approximations are implicit for interpreting the controlled partial differential equations. Numerical results were obtained using an effective Runge–Kutta method was developed using MATLAB software. This technique is commonly used to solve these problems since it is affordable, effective, and accurate to fourth order. Graphical interpretations are also used to calculate the effects of different physical parameters on temperature, concentration, velocity, dynamics of gyrotactic microorganisms, entropy generation, and Bejan number. Additionally, heat and mass characteristics of blood pumping were studied. According to certain results, entropy generation rises with the couple stress parameter. Furthermore, tables and bar charts are included to illustrate how certain data categories compare to earlier model-related research The findings indicated that gold nanoparticles are effective for drug transport as well as delivery systems due to their ability to control velocity using the thermophoresis and Brownian motion parameters. Gold nanoparticles additionally improve temperature dispersion, allowing it to damage cancer cells. In addition, the validity of findings is assured by reaching an agreement with earlier investigations. Flow, heat, and mass distributions are represented by streamlines, concentrations, and microorganisms. A graphical representation of the average Nusslet number and Sherwood number is also included. It is anticipated to provide a novel concept for improving the performance of controlling energy loss and improving the fluid's thermal performance are both critical in varied engineering applications. [ABSTRACT FROM AUTHOR]

Background Cedrol (CRL) is a sesquiterpene alcohol present in the essential oils of coniferous trees including Cupressus and Juniperus genera. CRL has shown potent anticancer activity by virtue of apoptosis. Red blood cells (RBCs), although devoid of mitochondria and nucleus, can undergo hemolysis and eryptosis which contribute to chemotherapy-induced anemia (CIA). In this work, we explored the hemolytic and eryptotic potential of CRL in human RBCs as a safety assessment of the sesquiterpene as an anticancer agent. Methods RBCs from healthy donors were treated with anticancer concentrations of CRL for 24 h at 37°C with varying experimental manipulations. Hemolysis was photometrically assessed by measuring hemoglobin release whereas flow cytometry was employed to detect phosphatidylserine (PS) exposure by annexin-V-FITC, intracellular Ca2+ by Fluo4/AM, cell volume by forward scatter (FSC), and oxidative stress by 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA). Results Significant, concentration-responsive hemolysis was noted upon CRL exposure with concomitant K+, LDH, and AST leakage. CRL also significantly increased annexin-V-positive cells and Fluo4 fluorescence and reduced FSC. Moreover, the cytotoxicity of CRL was significantly ameliorated in the presence of L-NAME, D4476, and PEG 8,000 but was aggravated by urea and sucrose. Conclusion CRL stimulates hemolysis and eryptosis characterized by PS exposure, Ca2+ overload, and cell shrinkage. The hemolytic activity of CRL was mediated through nitric oxide synthase and casein kinase 1a. Blocking either enzyme may attenuate the toxicity of CRL to RBCs and prevent undesirable side effects associated with its anticancer applications. [ABSTRACT FROM AUTHOR]

Background: Millions of patients undergo cardiac surgery each year. The red blood cell distribution width (RDW) could help predict the prognosis of patients who undergo percutaneous coronary intervention or coronary artery bypass surgery. We investigated whether the RDW has robust predictive value for the 30-day mortality among patients in an intensive care unit (ICU) after undergoing cardiac surgery. Methods: Using the Medical Information Mart for Intensive Care-IV Database, we retrieved data for 11,634 patients who underwent cardiac surgery in an ICU. We performed multivariate Cox regression analysis to model the association between the RDW and 30-day mortality and plotted Kaplan-Meier curves. Subgroup analyses were stratified using relevant covariates. Receiver operating characteristic (ROC) curves were used to determine the predictive value of the RDWs. Results: The total 30-day mortality rate was 4.2% (485/11,502). The elevated-RDW group had a higher 30-day mortality rate than the normal-RDW group (P <0.001). The robustness of our data analysis was confirmed by performing subgroup analyses. Each unit increase in the RDW was associated with a 17% increase in 30-day mortality when the RDW was used as a continuous variable (adjusted hazard ratio=1.17, 95% confidence interval, 1.10-1.25). Our ROC results showed the predictive value of the RDW. Conclusions: An elevated RDW was associated with a higher 30-day mortality in patients after undergoing cardiac surgery in an ICU setting. The RDW can serve as an efficient and accessible method for predicting the mortality of patients in ICUs following cardiac surgery. [ABSTRACT FROM AUTHOR]

Background: The Jra antigen is a high-prevalence red blood cell (RBC) antigen. Reports on cases of fatal hemolytic disease of the fetus and newborn and acute hemolytic transfusion reactions suggest that antibodies against Jra (anti-Jra) have potential clinical significance. Identifying anti-Jra is challenging owing to a lack of commercially available antisera. We developed an alternative approach to rapidly predict the presence of anti-Jra using the Taq-Man single-nucleotide polymorphism (SNP)-genotyping method. Methods: Residual peripheral blood samples from 10 patients suspected of having the anti-Jra were collected. Two samples with confirmed Jr(a-) RBCs and anti-Jra were used to validate the TaqMan genotyping assay by comparing the genotyping results with direct sequencing. The accuracy of the assay in predicting the presence of anti-Jra was verified through crossmatching with in-house Jr(a-) O+ RBCs. Results: The TaqMan-genotyping method was validated with two Jr(a-) RBC- and anti-Jraconfirmed samples that showed concordant Jra genotyping and direct sequencing results. Jra genotyping for the remaining samples and crossmatching the serum samples with inhouse Jr(a-) O+ RBCs showed consistent results. Conclusions: We validated a rapid, simple, accurate, and cost-effective method for predicting the presence of anti-Jra using a TaqMan-based SNP-genotyping assay. Implementing this method in routine practice in clinical laboratories will assist in solving difficult problems regarding alloantibodies to high-prevalence RBC antigens and ultimately aid in providing safe and timely transfusions and proper patient care. [ABSTRACT FROM AUTHOR]

During infection, the host employs nutritional immunity to restrict access to iron. Staphylococcus lugdunensis has been recognized for its ability to utilize host‐derived heme to overcome iron restriction. However, the mechanism behind this process involves the release of hemoglobin from erythrocytes, and the hemolytic factors of S. lugdunensis remain poorly understood. S. lugdunensis encodes four phenol‐soluble modulins (PSMs), short peptides with hemolytic activity. The peptides SLUSH A, SLUSH B, and SLUSH C are β‐type PSMs, and OrfX is an α‐type PSM. Our study shows the SLUSH locus to be essential for the hemolytic phenotype of S. lugdunensis. All four peptides individually exhibited hemolytic activity against human and sheep erythrocytes, but synergism with sphingomyelinase was observed exclusively against sheep erythrocytes. Furthermore, our findings demonstrate that SLUSH is crucial for allowing the utilization of erythrocytes as the sole source of nutritional iron and confirm the transcriptional regulation of SLUSH by Agr. Additionally, our study reveals that SLUSH peptides stimulate the human immune system. Our analysis identifies SLUSH as a pivotal hemolytic factor of S. lugdunensis and demonstrates its concerted action with heme acquisition systems to overcome iron limitation in the presence of host erythrocytes. [ABSTRACT FROM AUTHOR]

Ethnomedicinal plants are thought to have better prospects of harboring endophytes that produce natural products with pharmacological activities. This study aimed to investigate the antiplasmodial and anticancer properties of secondary metabolites of endophytic fungi from three medicinal plants. The endophytic fungi included Lasiodiplodia theobromae isolated from Cola acuminata, Curvularia lunata Bv4 isolated from Bambusa vulgaris, and Curvularia lunata Eg7 isolated from Elaeis guineensis. The identification of the fungi was based on the internal transcribed spacer (ITS-rDNA) sequence. The fungi were subjected to solid-state fermentation and the secondary metabolites were extracted with ethyl acetate. In vitro antiplasmodial screening of extracts was performed using the SYBR green I-based fluorescence assay on the chloroquine-resistant Plasmodium falciparum strain DD2. The cytotoxicity of the extracts on human red blood cells and Jurkat (leukemia) cells was assessed using the tetrazolium-based colorimetric MTT assay. Gas chromatography-mass spectrometry (GC–MS) analysis was used to identify the constituents of the fungal extracts. The extract of L. theobromae showed the best antiplasmodial activity against chloroquine-resistant P. falciparum (IC50 = 5.4 µg/mL) and was not harmful to erythrocytes (CC50 > 100 µg/mL). All three fungal extracts showed a weak cytotoxic effect against Jukart cell lines (CC50 > 100 µg/mL). GC–MS analysis of the three endophytic fungal extracts revealed the presence of forty major bioactive compounds, including: oxalic acid, isobutyl nonyl ester, 2,4-di-tert-butylphenol, and hexadecanoic acid, among others. The endophytic fungi from the medicinal plants in this study were promising sources of bioactive compounds that could be further evaluated as novel drugs for the treatment of malaria caused by P. falciparum-resistant strains. [ABSTRACT FROM AUTHOR]

Background: Feeding milk substitutes with low iron content or whole milk without iron supplementation is considered a major factor in developing iron-deficiency anemia in neonatal dairy calves. Young calves are often supplemented with iron dextran injections on the first day of life to prevent anemia. However, the effects of preventive treatment and the presence of disease on serum iron (Fe) concentrations, serum ferritin levels, and hematological blood parameters during the early neonatal stages have not been examined in detail. Therefore, we examined and evaluated the effects of iron dextran injections and health status on the development of hematocrit (Ht), red blood cells (RBC), hemoglobin concentration (Hb), erythrocyte indices (mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration), Fe, and serum ferritin concentrations in dairy calves within the first 10 days of life. The suitability of serum ferritin as a reliable indicator of anemia in very young calves was evaluated by correlating ferritin concentrations with known laboratory diagnostic parameters of anemia. Results: Iron supplementation significantly increased Fe levels (P = 0.048) but did not affect serum ferritin levels in neonatal calves. Fe concentrations were significantly lower in diseased than healthy calves (P = 0.0417). Iron supplementation significantly affected the health status, as observed in Ht (Ptreat=0.0057; Phealth=0.0097), RBC (Ptreat=0.0342; Phealth=0.0243), and Hb (Ptreat=0.0170; Phealth=0.0168). Serum ferritin levels did not significantly correlate with Fe levels. Both groups showed marked differences in ferritin levels, with the highest levels measured on day 2. Fe concentrations showed weak negative correlations with Hb and Ht levels on day 3 (ρ=-0.45; P = 0.0034 and ρ=-0.045; P = 0.0032, respectively). RBC count showed strong positive correlations with Hb and Ht levels (ρ = 0.91 and ρ = 0.93; P < 0.001). Conclusion: Iron dextran injections increased Fe concentrations but reduced Ht level, RBC count, and Hb level. The presence of diseases led to a reduction in Fe and higher values of Ht, RBC, and Hb in moderate disease than in severe disease. Due to physiological fluctuations during the first 3 days of life, serum ferritin level seems unuseful for evaluating iron storage before day 4 of life. [ABSTRACT FROM AUTHOR]

Background Methods Results Discussion Normothermic regional perfusion (NRP) and normothermic machine perfusion (NMP) are organ procurement and transport techniques that can improve organ quality, facilitate longer transport, and reduce postoperative complications, increasing organ availability and improving outcomes. NRP and NMP often require allogeneic red blood cells (RBCs). Our academic transfusion service began providing RBCs to support NRP and NMP for adult heart transplant (HT), orthotopic liver transplant (OLT), and multiorgan transplant (MOT) in August 2020.This single‐center, retrospective study describes the implementation process and analyzes the characteristics of RBC support during the first 3 years of the perfusion programs. Timing and quantity of units issued and used, organ recipient demographics, and transplant outcomes were obtained from transfusion service and electronic medical records.From 2020 to 2023, the transfusion service received 233 requests to support NRP and NMP perfusion cases. Of these, 105 cases resulted in RBC use, and units were returned or discarded in 112 cases. A total of 131 patients received perfusion‐facilitated transplants (92 HT, 27 OLT, and 12 MOT). The majority of perfusion‐facilitated HTs utilized NRP (81/92, 88%), whereas most perfusion‐facilitated OLTs utilized NMP (21/27, 78%). Across all 233 requests, a total of 381 RBC units were used to facilitate 131 transplants, averaging 2.91 units/transplant.Provision of RBCs for NRP and NMP techniques represents a novel method for transfusion services to support and facilitate life‐saving organ transplants with only modest product use, about three RBC units per organ transplant in this single‐center study. [ABSTRACT FROM AUTHOR]

Background: Circulatory shock, defined as decreased tissue perfusion, leading to inadequate oxygen delivery to meet cellular metabolic demands, remains a common condition with high morbidity and mortality. Rapid restitution and restoration of adequate tissue perfusion are the main treatment goals. To achieve this, current hemodynamic strategies focus on adjusting global physiological variables such as cardiac output (CO), hemoglobin (Hb) concentration, and arterial hemoglobin oxygen saturation (SaO2). However, it remains a challenge to identify optimal targets for these global variables that best support microcirculatory function. Weighting up the risks and benefits is especially difficult for choosing the amount of oxygen supplementation in critically ill patients. This review assesses the physiological basis for oxygen delivery to the tissue and provides an overview of the relevant literature to emphasize the importance of considering risks and benefits and support decision making at the bedside. Physiological premises: Oxygen must reach the tissue to enable oxidative phosphorylation. The human body timely detects hypoxia via different mechanisms aiming to maintain adequate tissue oxygenation. In contrast to the pulmonary circulation, where the main response to hypoxia is arteriolar vasoconstriction, the regulatory mechanisms of the systemic circulation aim to optimize oxygen availability in the tissues. This is achieved by increasing the capillary density in the microcirculation and the capillary hematocrit thereby increasing the capacity of oxygen diffusion from the red blood cells to the tissue. Hyperoxia, on the other hand, is associated with oxygen radical production, promoting cell death. Current state of research: Clinical trials in critically ill patients have primarily focused on comparing macrocirculatory endpoints and outcomes based on stroke volume and oxygenation targets. Some earlier studies have indicated potential benefits of conservative oxygenation. Recent trials show contradictory results regarding mortality, organ dysfunction, and ventilatory-free days. Empirical studies comparing various targets for SaO2, or partial pressure of oxygen indicate a U-shaped curve balancing positive and negative effects of oxygen supplementation. Conclusion and future directions: To optimize risk–benefit ratio of resuscitation measures in critically ill patients with circulatory shock in addition to individual targets for CO and Hb concentration, a primary aim should be to restore tissue perfusion and avoid hyperoxia. In the future, an individualized approach with microcirculatory targets will become increasingly relevant. Further studies are needed to define optimal targets. [ABSTRACT FROM AUTHOR]

Background: The effect of a liberal transfusion strategy as compared with a restrictive strategy on outcomes in critically ill patients with traumatic brain injury is unclear. Methods: We randomly assigned adults with moderate or severe traumatic brain injury and anemia to receive transfusion of red cells according to a liberal strategy (transfusions initiated at a hemoglobin level of =10 g per deciliter) or a restrictive strategy (transfusions initiated at =7 g per deciliter). The primary outcome was an unfavorable outcome as assessed by the score on the Glasgow Outcome Scale-Extended at 6 months, which we categorized with the use of a sliding dichotomy that was based on the prognosis of each patient at baseline. Secondary outcomes included mortality, functional independence, quality of life, and depression at 6 months. Results: A total of 742 patients underwent randomization, with 371 assigned to each group. The analysis of the primary outcome included 722 patients. The median hemoglobin level in the intensive care unit was 10.8 g per deciliter in the group assigned to the liberal strategy and 8.8 g per deciliter in the group assigned to the restrictive strategy. An unfavorable outcome occurred in 249 of 364 patients (68.4%) in the liberal-strategy group and in 263 of 358 (73.5%) in the restrictive-strategy group (adjusted absolute difference, restrictive strategy vs. liberal strategy, 5.4 percentage points; 95% confidence interval, -2.9 to 13.7). Among survivors, a liberal strategy was associated with higher scores on some but not all the scales assessing functional independence and quality of life. No association was observed between the transfusion strategy and mortality or depression. Venous thromboembolic events occurred in 8.4% of the patients in each group, and acute respiratory distress syndrome occurred in 3.3% and 0.8% of patients in the liberal-strategy and restrictive-strategy groups, respectively. Conclusions: In critically ill patients with traumatic brain injury and anemia, a liberal transfusion strategy did not reduce the risk of an unfavorable neurologic outcome at 6 months. (Funded by the Canadian Institutes of Health Research and others; HEMOTION ClinicalTrials.gov number, NCT03260478.). [ABSTRACT FROM AUTHOR]

The band 3 transporter is a critical integral membrane protein of the red blood cell (RBC), as it is responsible for catalyzing the exchange of bicarbonate and chloride anions across the plasma membrane. To elucidate the structural mechanism of the band 3 transporter, detergent solubilized human ghost membrane reconstituted in nanodiscs was applied to a cryo-EM holey carbon grid to define its composition. With this approach, we identified and determined structural information of the human band 3 transporter. Here, we present 5 different cryo-EM structures of the transmembrane domain of dimeric band 3, either alone or bound with chloride or bicarbonate. Interestingly, we observed that human band 3 can form both symmetric and asymmetric dimers with a different combination of outward-facing (OF) and inward-facing (IF) states. These structures also allow us to obtain the first model of a human band 3 molecule at the IF conformation. Based on the structural data of these dimers, we propose a model of ion transport that is in favor of the elevator-type mechanism. Previous studies have solved the high-resolution structures of the dimeric band 3 transporter, but the ion transport mechanism has not yet been fully elucidated. This study solves several cryo-EM structures of band 3 in different conformations indicating that the ion transport mechanism involves the concerted movement of chloride and bicarbonate ions. [ABSTRACT FROM AUTHOR]

Haematological investigation is an important component of stress and immune response assessment and holds great potential for evaluating amphibian welfare. The olm (Proteus anguinus) is a neotenic, cave-dwelling salamander endemic to the Dinaric Karst and classified as a vulnerable species by the IUCN. The aim of the present study was to gain basic knowledge about the haematology of this endangered species and to establish reference values of leucocyte differential counts. Blood smears were obtained from recently captured animals and compared to smears from the same animals in long-term captivity (up to five years). The elongated erythrocytes are nucleated and are among the largest in vertebrates, which is also reflected in their lower concentration per millilitre of blood. The circulating blood can contain mitotically active, immature erythrocytes (erythroblasts), indicating that erythrocytes of the olm can undergo proliferation and maturation in circulating blood. Olms show a typical urodele leucocyte profile, with lymphocytes predominating, followed by neutrophils, although the proportion of lymphocytes is higher than in other urodeles. Eosinophil and monocyte counts were relatively low, while basophils were nearly absent. We found no statistically significant differences in leucocyte counts or in neutrophil to lymphocyte ratio neither between recently captured olms and same animals during captivity nor between the sexes, except for lower neutrophil count in captive females. Thus, no differences in stress levels between recently captured olms and captive olms were detected via haematological investigations. The significance of these results is discussed in the context of detecting stress and immune responses in olms. [ABSTRACT FROM AUTHOR]

Background and Objectives Materials and Methods Results Conclusion Preoperative red blood cell (RBC) transfusions increase post‐operative venous thromboembolic (VTE) events. Erythropoietin‐stimulating agents (ESAs) increase VTE risk in cancer patients; we aimed to assess ESA versus RBC‐associated VTE risks in a broad population of surgical patients.We queried TriNetX Diamond Network from 2006 to 2023, comparing patients with anaemia within 3 months preoperatively who received preoperative ESAs with or without intravenous (IV) iron to patients who received preoperative RBCs. Sub‐analyses included (1) all surgeries and (2) cardiovascular surgeries.We propensity score matched for demographics, comorbidities, medical services, post‐treatment haemoglobin (g/dL) and, for all‐surgery comparisons, surgery type. Outcomes included 30‐day post‐operative mortality, VTE, pulmonary embolism (PE), disseminated intravascular coagulation (DIC) and haemoglobin.In our 19,548‐patient cohorts, compared with preoperative RBC transfusion, ESAs without IV iron were associated with lower mortality (relative risk [RR] = 0.51 [95% confidence interval (CI), 0.45–0.59]), VTE (RR = 0.57 [0.50–0.65]) and PE (RR = 0.67 [0.54–0.84]). Post‐operative haemoglobin was higher in the ESA without IV iron cohort compared with the transfusion cohort (10.0 ± 1.4 vs. 9.4 ± 1.8 g/dL, p = 0.002). Cardiac surgical patients receiving ESAs with or without IV iron had lower risk for post‐operative mortality, VTE and PE (p < 0.001) than those receiving RBCs. Post‐operative haemoglobin differed between patients receiving ESAs with IV iron versus RBCs (10.1 ± 1.5 vs. 9.4 ± 1.9 g/dL, p = 0.0009).Compared with surgical patients who were transfused RBCs, ESA recipients had reduced 30‐day post‐operative risk of mortality, VTE, PE and DIC and increased haemoglobin levels. IV iron given with ESAs improved mortality. [ABSTRACT FROM AUTHOR]

This article presents a case report of a patient with immune-mediated thrombotic thrombocytopenic purpura (iTTP), a potentially life-threatening blood clotting disorder. The patient experienced a stroke before developing low platelet count and abnormal red blood cell breakdown. The article emphasizes the importance of early diagnosis and treatment to prevent further organ damage. The patient was successfully treated with therapeutic plasma exchange, prednisolone, and caplacizumab, which improved platelet count and resolved the abnormal red blood cell breakdown. The article also discusses how this case challenges the typical presentation of the disorder and suggests a potential mechanism for organ damage in iTTP. The study received funding from the Ministry of Health, Labour and Welfare of Japan. [Extracted from the article]

Objective: Patients with mild oral and maxillofacial space infection (OMSI) usually need only antimicrobial therapy. However, surgical intervention is eventually needed after using antibiotics for a period. The objective of this study was to explore the risk factors for drug therapy failure in OMSI. Subjects and methods: A retrospective case‒control study was designed. From August 2020 to September 2022, patients at Shanghai Jiao Tong University Affiliated Ninth People's Hospital who were diagnosed with OMSI were retrospectively reviewed. The outcome variable was surgical intervention after the use of antibiotics. We collected common biological factors, including demographic characteristics, routine blood test results, C-reactive protein (CRP) levels and composite indicators, such as neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR). The χ2 test and binary logistic regression were used to examine the association between biological factors and the outcome variable. Results: Forty-six patients were included in this study. Further surgical intervention was needed in 20 patients (43.5%). The NLR showed a significant association with further surgical drainage (p = 0.01). A binary logistic regression equation was found by using stepwise regression based on the Akaike information criterion (R2 = 0.443), which was associated with sex (odds ratio [OR], 0.216; p = 0.092), NLR (OR, 1.258; p = 0.045), red blood cell (RBC) count (OR, 4.372; p = 0.103) and monocyte (MONO) count (OR, 9.528, p = 0.023). Receiver operating characteristic analysis produced an area under the curve for NLR of 0.725 (p = 0.01) and for the binary logistic regression model of 0.8365 (p < 0.001). Conclusion: Surgical interventions are needed in some mild OMSI patients when antimicrobial therapy fails to stop the formation of abscesses. The binary logistic regression model shows that NLR can be used as an ideal prognostic factor to predict the outcome of antimicrobial therapy and the possibility of requiring surgical intervention. Statement of clinical relevance: Using simple, inexpensive, and easily achieved biological parameters (such as routine blood test results) and composite indicators calculated by them (such as NLR) to predict whether surgical intervention is needed in the future provides a reference for clinical doctors and enables more cost-effective and efficient diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Malnutrition is linked to adverse outcomes in post-cardiac surgery patients. This study investigates the correlation between the Geriatric Nutritional Risk Index (GNRI) and adverse hospital outcomes in patients following cardiac surgery. This retrospective study included elderly patients with heart disease who were admitted to the Department of Cardiology, Fujian Medical University Union Hospital from January 2020 to December 2022. Patients were divided into two groups based on the cut-off value (98 g/dL). Data from 407 patients were assessed, with 278 (68.3%) classified as having nutritional risk and 129 (31.7%) as having no nutritional risk. Notable distinctions were observed in body weight, BMI, and left ventricular ejection fraction (P < 0.05). Laboratory indicators indicated lower levels of serum albumin, lymphocytes, red blood cells, hemoglobin, admission blood glucose, and admission triglyceride in the nutritional risk group (P < 0.05). Neutrophils and serum creatinine were higher in the nutritional risk group (P < 0.05). Poor prognosis was prevalent in the nutrition risk group (64.7%), with higher incidences of adverse outcomes (P < 0.05). Univariate and multivariate studies showed that GNRI < 98 g/dL was an independent predictor of postoperative cardiac surgery. Nutritional risk was an important predictor of adverse hospital outcomes after the surgery. [ABSTRACT FROM AUTHOR]

To explore preoperative and operative risk factors for red blood cell (RBC) transfusion requirements during liver transplantation (LT) and up to 24 h afterwards. We evaluated the associations between risk factors and units of RBC transfused in 176 LT patients using a log-binomial regression model. Relative risk was adjusted for age, sex, and the model for end-stage liver disease score (MELD) (adjustment 1) and baseline hemoglobin concentration (adjustment 2). Forty-six patients (26.14%) did not receive transfusion. Grafts from cardiac-death donors were used in 32.61% and 31.54% of non-transfused and transfused patients, respectively. The transfused group required more reoperation for bleeding (P = 0.035), longer mechanical ventilation after LT (P < 0.001), and longer ICU length of stay (P < 0.001). MELD and hemoglobin concentrations determined RBC requirements. For each unit of increase in the MELD score, 2% more RBC units were transfused, and non-transfusion was 0.83-fold less likely. For each 10-g/L higher hemoglobin concentration at baseline, 16% less RBC transfused, and non-transfusion was 1.95-fold more likely. Ascites was associated with 26% more RBC transfusions. With an increase of 2 mm from the baseline in the A10Fibtem measurement of maximum clot firmness, non-transfusion was 1.14-fold more likely. A 10-min longer cold ischemia time was associated with 1% more RBC units transfused, and the presence of post-reperfusion syndrome with 45% more RBC units. We conclude that preoperative correction of anemia should be included in LT. An intervention to prevent severe hypotension and fibrinolysis during graft reperfusion should be explored. Trial register: European Clinical Trials Database (EudraCT 2018–002,510-13) and ClinicalTrials.gov (NCT01539057). [ABSTRACT FROM AUTHOR]

The main objective of this work is to synthesize multifunctional nanodendritic structural molecules that can effectively encapsulate hydrophilic as well as hydrophobic therapeutic agents. Four different types of fourth-generation lysine-citric acid based dendrimer have been synthesized in this work: PE-MC-Lys-CA-PEG, TMP-MC-Lys-CA-PEG, PE-MS-Lys-CA-PEG, and TMP-MS-Lys-CA-PEG. The antibacterial drug cefotaxime (CFTX) was further conjugated to these dendrimers. The dendrimer and drug-dendrimer conjugate structures were characterized with the help of FTIR,1H-NMR, and 13C-NMR spectroscopy. Zeta sizer, AFM, and HR-TEM techniques were used to investigate the particle size, surface topography, and structural characteristics of drug-dendrimer conjugates. In vitro drug release was then investigated using dialysis method. Various kinetic drug release models were examined to evaluate the type of kinetic drug release mechanism of the formulations. Cytotoxicity study revealed that the dendrimers encapsulated with CFTX exhibited 2-3% toxicity against healthy epithelial cells, indicating their safe use. Plain dendrimers show 10-15% hemolytic toxicity against red blood cells (RBC), and the toxicity was reduced to 2-3% when CFTX was conjugated to the same dendrimers. The 3rd and 4th generation synthesized drug-dendrimer conjugates exhibit a significantly effective zone of inhibition (ZOI) against both Gram-positive and Gram-negative bacteria. For Gram-positive bacteria, the lower concentration of 0.1 mg/mL showed more than 98% inhibition of drug-dendrimer conjugate samples against B. subtilis and more than 50% inhibition against S. aureus using 0.2 mg/mL, respectively. Moreover, samples with concentrations of 0.5 and 1.0 mg/mL exhibited more than 50% inhibition against S. typhimurium and E. coli, respectively. [ABSTRACT FROM AUTHOR]

Objectives: Experimental and acute exposure studies imply that manganese affects red blood cell production. Nevertheless, the association between environmental exposure and red blood cell distribution width (RDW) has yet to be explored. This research sought to assess the correlation between blood manganese levels and RDW within the general population of the United States. Materials and methods: Employing weighted multiple linear regression models, data from the 2011–2018 National Health and Nutrition Examination Survey (NHANES) were utilized to assess the correlation between manganese levels in the blood and RDW. Restricted cubic spline plots and two-piecewise linear regression models were also employed. Result: The analysis included a total of 15882 participants in which we determined an independent positive relationship between blood manganese levels and RDW among participants(β = 0.079, P<0.001). Moreover, we identified a J-shaped association between blood manganese levels and RDW in total participants (inflection point for blood manganese: 7.32 ug/L) and distinct subgroups following adjusted covariates. Women exhibited a more pronounced association, even after controlling for adjusted covariates. Conclusions: We determined a J-shaped relationship between blood manganese levels and RDW with an inflection point at 7.32 ug/L for blood manganese. Nevertheless, fundamental research and large sample prospective studies are needed to determine the extent to which blood manganese levels correlate with RDW. [ABSTRACT FROM AUTHOR]

Non-coding RNA expression has shown to have cell type-specificity. The regulatory characteristics of these molecules are impacted by changes in their expression levels. We performed next-generation sequencing and examined small RNA-seq data obtained from 6 different types of blood cells separated by fluorescence-activated cell sorting of severe COVID−19 patients and healthy control donors. In addition to examining the behavior of piRNA in the blood cells of severe SARS-CoV−2 infected patients, our aim was to present a distinct piRNA differential expression portrait for each separate cell type. We observed that depending on the type of cell, different sorted control cells (erythrocytes, monocytes, lymphocytes, eosinophils, basophils, and neutrophils) have altering piRNA expression patterns. After analyzing the expression of piRNAs in each set of sorted cells from patients with severe COVID−19, we observed 3 significantly elevated piRNAs - piR−33,123, piR−34,765, piR−43,768 and 9 downregulated piRNAs in erythrocytes. In lymphocytes, all 19 piRNAs were upregulated. Monocytes were presented with a larger amount of statistically significant piRNA, 5 upregulated (piR−49039 piR−31623, piR−37213, piR−44721, piR−44720) and 35 downregulated. It has been previously shown that piR−31,623 has been associated with respiratory syncytial virus infection, and taking in account the major role of piRNA in transposon silencing, we presume that the differential expression patterns which we observed could be a signal of indirect antiviral activity or a specific antiviral cell state. Additionally, in lymphocytes, all 19 piRNAs were upregulated. [ABSTRACT FROM AUTHOR]

Background: Sirolimus is increasingly utilized in treating diseases associated with mTOR pathway overactivation. Despite its potential, the lack of evidence regarding its long-term safety across all age groups, particularly in pediatric patients, has limited its further application. This study aims to assess the long-term safety of sirolimus, with a specific focus on its impact on growth patterns in pediatric patients. Methods: This pooled analysis inlcudes two prospective cohort studies spanning 10 years, including 1,738 participants (aged 5 days to 69 years) diagnosed with tuberous sclerosis and/or lymphangioleiomyomatosis. All participants were mTOR inhibitor-naive and received 1 mg/m²/day of sirolimus, with dose adjustments during a two-week titration period to maintain trough blood concentrations between 5 and 10 ng/ml (maximum dose 2 mg). Indicators of physical growth, hematopoietic, liver, renal function, and blood lipid levels were all primary outcomes and were analyzed. The adverse events and related management were also recorded. Results: Sirolimus administration did not lead to deviations from normal growth ranges, but higher doses exhibited a positive association with Z-scores exceeding 2 SD in height, weight, and BMI. Transient elevations in red blood cell and white blood cell counts, along with hyperlipidemia, were primarily observed within the first year of treatment. Other measured parameters remained largely unchanged, displaying only weak correlations with drug use. Stomatitis is the most common adverse event (920/1738, 52.9%). In adult females, menstrual disorders were observed in 48.5% (112/217). Conclusions: Sirolimus's long-term administration is not associated with adverse effects on children's physical growth pattern, nor significant alterations in hematopoietic, liver, renal function, or lipid levels. A potential dose-dependent influence on growth merits further exploration. Trial registration: Pediatric patients: Chinese clinical trial registry, No. ChiCTR-OOB-15,006,535. Adult patients: ClinicalTrials, No. NCT03193892. [ABSTRACT FROM AUTHOR]

This correction notice addresses an error in the publication of an article titled "Antimicrobial resistance among indicator Enterococcus faecium and Escherichia coli in Swedish pig farms." The correction pertains to the incorrect presentation of Figures 1 and 2 in the original article. The corrected versions of the figures are provided, and the original article has been updated accordingly. The correction notice concludes with a statement from the publisher, Springer Nature, emphasizing their neutrality in relation to jurisdictional claims and institutional affiliations. The authors of the article are Valeriia Ladyhina, Susanna Sternberg-Lewerin, Linus Andersson, and Elisabeth Rajala. [Extracted from the article]

Staphylococcus epidermidis is a particular concern due to its high resistance to most antibiotics. We designed and synthesised a series of nitrofuran derivatives based on the chemical structure of nitrofurantoin. Among these derivatives, compared to nitrofurantoin, the nitrofuran derivatives with n‐alkyl groups did not effectively inhibit S. aureus with minimum inhibitory concentrations (MIC) values ranging from 16 to >128 μM, while these with benzyl groups displayed potent antibacterial activity against S. aureus with MIC values ranging from 4 to 16 μM. It suggests benzyl groups play an important role in the nitrofuran derivatives against S. aureus. The nitrofuran derivatives with benzyl groups also displayed potent antibacterial activity against S. epidermidis with MIC values ranging from 2 to 8 μM. Especially, compound 20 exhibited MIC 2 μM (0.814 μg/mL) against S. epidermidis. The CC50s of compound 20 in 293 T cells and LX‐2 cells were 3.131 μg/mL and 30.51 μg/mL, respectively. While at 128 μg/mL of compound 20, no obvious red blood cell rupture was observed. It showed minimal cytotoxicity and hemolytic activity. These findings suggest that compound 20 could function as a potential antibacterial agent for treating Urinary tract infections (UTIs) caused by S. epidermidis. [ABSTRACT FROM AUTHOR]

Introduction: Oligomeric alpha-synuclein in red blood cells (RBC-o-α-Syn) has been shown to be increased in patients with Parkinson's disease (PD). However, factors that affect RBC-o-α-Syn levels remain to be elucidated. The aim of this study is to analyze the correlations between RBC-o-α-Syn levels and the age, sex and different clinical variables of patients with PD. Methods: 167 patients with PD and 119 healthy controls (HC) were enrolled in this study. The patients with PD were diagnosed based on the MDS clinical diagnostic criteria for PD. All participants were evaluated for their clinical characteristics. Western blot analysis was used to examine the molecular sizes of RBC-o-α-Syn. A newly established chemiluminescent immunoassay was used to measure RBC-o-α-Syn levels. Results: Higher RBC-o-α-Syn levels were detected in PD patients than in HC subjects. The receiver operating characteristic (ROC) curve indicated that a cut off value of 55.29 ng/mg discriminated well between PD patients and HC subjects, with a sensitivity of 67.66% (95% CI: 60.24-74.29%), a specificity of 88.24% (95% CI: 81.22-92.86%), and an area under the curve (AUC) of 0.857. The levels of RBC-o-α-Syn were higher in female than male patients (p = 0.033). For different subtypes, the levels of RBC-o-α-Syn were higher in the MIX subtype than the tremor-dominant (TD) PD. In addition, the levels of RBC-o-α-Syn were higher in patients with than without cognitive impairment (p = 0.016), and negatively correlated with Mini-Mental State Examination (MMSE) scores (r = -0.156, p = 0.044). Conclusion: Our study demonstrates that RBC-o-α-Syn levels in patients with PD are higher than those in HC subjects and affected by the sex and the severity of cognitive impairment. [ABSTRACT FROM AUTHOR]

This review focuses on the role of human red blood cells (RBCs) as drug carriers. First, a general introduction about RBC physiology is provided, followed by the presentation of several cases in which RBCs act as natural carriers of drugs. This is due to the presence of several binding sites within the same RBCs and is regulated by the diffusion of selected compounds through the RBC membrane and by the presence of influx and efflux transporters. The balance between the influx/efflux and the affinity for these binding sites will finally affect drug partitioning. Thereafter, a brief mention of the pharmacokinetic profile of drugs with such a partitioning is given. Finally, some examples in which these natural features of human RBCs can be further exploited to engineer RBCs by the encapsulation of drugs, metabolites, or target proteins are reported. For instance, metabolic pathways can be powered by increasing key metabolites (i.e., 2,3-bisphosphoglycerate) that affect oxygen release potentially useful in transfusion medicine. On the other hand, the RBC pre-loading of recombinant immunophilins permits increasing the binding and transport of immunosuppressive drugs. In conclusion, RBCs are natural carriers for different kinds of metabolites and several drugs. However, they can be opportunely further modified to optimize and improve their ability to perform as drug vehicles. [ABSTRACT FROM AUTHOR]