Two-component macrophage model for active phagocytosis with pseudopod formation.

Macrophage phagocytosis is critical for the immune response, homeostasis regulation, and tissue repair. This intricate process involves complex changes in cell morphology, cytoskeletal reorganization, and various receptor-ligand interactions controlled by mechanical constraints. However, there is a lack of comprehensive theoretical and computational models that investigate the mechanical process of phagocytosis in the context of cytoskeletal rearrangement. To address this issue, we propose a novel coarse-grained mesoscopic model that integrates a fluid-like cell membrane and a cytoskeletal network to study the dynamic phagocytosis process. The growth of actin filaments results in the formation of long and thin pseudopods, and the initial cytoskeleton can be disassembled upon target entry and reconstructed after phagocytosis. Through dynamic changes in the cytoskeleton, our macrophage model achieves active phagocytosis by forming a phagocytic cup utilizing pseudopods in two distinct ways. We have developed a new algorithm for modifying membrane area to prevent membrane rupture and ensure sufficient surface area during phagocytosis. In addition, the bending modulus, shear stiffness, and cortical tension of the macrophage model are investigated through computation of the axial force for the tubular structure and micropipette aspiration. With this model, we simulate active phagocytosis at the cytoskeletal level and investigate the mechanical process during the dynamic interplay between macrophage and target particles.

A combined computational and experimental investigation of the filtration function of splenic macrophages in sickle cell disease.

Being the largest lymphatic organ in the body, the spleen also constantly controls the quality of red blood cells (RBCs) in circulation through its two major filtration components, namely interendothelial slits (IES) and red pulp macrophages. In contrast to the extensive studies in understanding the filtration function of IES, fewer works investigate how the splenic macrophages retain the aged and diseased RBCs, i.e., RBCs in sickle cell disease (SCD). Herein, we perform a computational study informed by companion experiments to quantify the dynamics of RBCs captured and retained by the macrophages. We first calibrate the parameters in the computational model based on microfluidic experimental measurements for sickle RBCs under normoxia and hypoxia, as those parameters are not available in the literature. Next, we quantify the impact of key factors expected to dictate the RBC retention by the macrophages in the spleen, namely, blood flow conditions, RBC aggregation, hematocrit, RBC morphology, and oxygen levels. Our simulation results show that hypoxic conditions could enhance the adhesion between the sickle RBCs and macrophages. This, in turn, increases the retention of RBCs by as much as four-fold, which could be a possible cause of RBC congestion in the spleen of patients with SCD. Our study on the impact of RBC aggregation illustrates a 'clustering effect', where multiple RBCs in one aggregate can make contact and adhere to the macrophages, leading to a higher retention rate than that resulting from RBC-macrophage pair interactions. Our simulations of sickle RBCs flowing past macrophages for a range of blood flow velocities indicate that the increased blood velocity could quickly attenuate the function of the red pulp macrophages on detaining aged or diseased RBCs, thereby providing a possible rationale for the slow blood flow in the open circulation of the spleen. Furthermore, we quantify the impact of RBC morphology on their tendency to be retained by the macrophages. We find that the sickle and granular-shaped RBCs are more likely to be filtered by macrophages in the spleen. This finding is consistent with the observation of low percentages of these two forms of sickle RBCs in the blood smear of SCD patients. Taken together, our experimental and simulation results aid in our quantitative understanding of the function of splenic macrophages in retaining the diseased RBCs and provide an opportunity to combine such knowledge with the current knowledge of the interaction between IES and traversing RBCs to apprehend the complete filtration function of the spleen in SCD.

Single-cell characterization of deformation and dynamics of mesenchymal stem cells in microfluidic systems: A computational study.

Understanding the homing dynamics of individual mesenchymal stem cells (MSCs) in physiologically relevant microenvironments is crucial for improving the efficacy of MSC-based therapies for therapeutic and targeting purposes. This study investigates the passive homing behavior of individual MSCs in micropores that mimic interendothelial clefts through predictive computational simulations informed by previous microfluidic experiments. Initially, we quantified the size-dependent behavior of MSCs in micropores and elucidated the underlying mechanisms. Subsequently, we analyzed the shape deformation and traversal dynamics of each MSC. In addition, we conducted a systematic investigation to understand how the mechanical properties of MSCs impact their traversal process. We considered geometric and mechanical parameters, such as reduced cell volume, cell-to-nucleus diameter ratio, and cytoskeletal prestress states. Furthermore, we quantified the changes in the MSC traversal process and identified the quantitative limits in their response to variations in micropore length. Taken together, the computational results indicate the complex dynamic behavior of individual MSCs in the confined microflow. This finding offers an objective way to evaluate the homing ability of MSCs in an interendothelial-slit-like microenvironment.

In silico and in vitro study of the adhesion dynamics of erythrophagocytosis in sickle cell disease.

Erythrophagocytosis occurring in the spleen is a critical process for removing senescent and diseased red blood cells (RBCs) from the microcirculation. Although some progress has been made in understanding how the biological signaling pathways mediate the phagocytic processes, the role of the biophysical interaction between RBCs and macrophages, particularly under pathological conditions such as sickle cell disease, has not been adequately studied. Here, we combine computational simulations with microfluidic experiments to quantify RBC-macrophage adhesion dynamics under flow conditions comparable to those in the red pulp of the spleen. We also investigate the RBC-macrophage interaction under normoxic and hypoxic conditions. First, we calibrate key model parameters in the adhesion model using microfluidic experiments for normal and sickle RBCs under normoxia and hypoxia. We then study the adhesion dynamics between the RBC and the macrophage. Our simulation illustrates three typical adhesion states, each characterized by a distinct dynamic motion of the RBCs, namely firm adhesion, flipping adhesion, and no adhesion (either due to no contact with macrophages or detachment from the macrophages). We also track the number of bonds formed when RBCs and macrophages are in contact, as well as the contact area between the two interacting cells, providing mechanistic explanations for the three adhesion states observed in the simulations and microfluidic experiments. Furthermore, we quantify, for the first time to our knowledge, the adhesive forces between RBCs (normal and sickle) and macrophages under different oxygenated conditions. Our results show that the adhesive forces between normal cells and macrophages under normoxia are in the range of 33-58 pN and 53-92 pN for sickle cells under normoxia and 155-170 pN for sickle cells under hypoxia. Taken together, our microfluidic and simulation results improve our understanding of the biophysical interaction between RBCs and macrophages in sickle cell disease and provide a solid foundation for investigating the filtration function of the splenic macrophages under physiological and pathological conditions.

Polycyclic Aromatic Hydrocarbons as a New Class of Promising Cathode Materials for Aluminum-Ion Batteries.

As an emerging post-lithium battery technology, aluminum ion batteries (AIBs) have the advantages of large Al reserves and high safety, and have great potential to be applied to power grid energy storage. But current graphite cathode materials are limited in charge storage capacity due to the formation of stage-4 graphite-intercalated compounds (GICs) in the fully charged state. Herein, we propose a new type of cathode materials for AIBs, namely polycyclic aromatic hydrocarbons (PAHs), which resemble graphite in terms of the large conjugated π bond, but do not form GICs in the charge process. Quantum chemistry calculations show that PAHs can bind AlCl4 - through the interaction between the conjugated π bond in the PAHs and AlCl4 - , forming on-plane interactions. The theoretical specific capacity of PAHs is negatively correlated with the number of benzene rings in the PAHs. Then, under the guidance of theoretical calculations, anthracene, a three-ring PAH, was evaluated as a cathode material for AIBs. Electrochemical measurements show that anthracene has a high specific capacity of 157 mAh g-1 (at 100 mA g-1 ) and still maintains a specific capacity of 130 mAh g-1 after 800 cycles. This work provides a feasible "theory guides practice" research model for the development of energy storage materials, and also provides a new class of promising cathode materials for AIBs.

Boosting the Cycling Stability of Aqueous Flexible Zn Batteries via F Doping in Nickel-Cobalt Carbonate Hydroxide Cathode.

Cathodes of rechargeable Zn batteries typically face the issues of irreversible phase transformation, structure collapse, and volume expansion during repeated charge/discharge cycles, which result in an increased transfer resistance and poor long-term cycling stability. Herein, a facile F doping strategy is developed to boost the cycling stability of nickel cobalt carbonate hydroxide (NiCo-CH) cathode. Benefiting from the extremely high electronegativity, the phase and morphology stabilities as well as the electrical conductivity of NiCo-CH are remarkably enhanced by F incorporation (NiCo-CH-F). Phase interface and amorphous microdomains are also introduced, which are favorable for the electrochemical performance of cathode. Benefiting from these features, NiCo-CH-F delivers a high capacity (245 mA h g-1 ), excellent rate capability (64% retention at 8 A g-1 ), and outstanding cycling stability (maintains 90% after 10 000 cycles). Moreover, the quasi-solid-state battery also manifests superior cycling stability (maintains 90% after 7200 cycles) and desirable flexibility. This work offers a general strategy to boost the cycling stability of cathode materials for aqueous Zn batteries.

Understanding the Twisted Structure of Amyloid Fibrils via Molecular Simulations.

Accumulation and aggregation of amyloid are associated with the pathogenesis of many human diseases, such as Alzheimer's disease and Type 2 diabetes mellitus. Therefore, a quantitative understanding of the molecular mechanisms causing different aggregated structures and biomechanical properties of amyloid fibrils could shed some light into the progression of these diseases. In this work, we develop coarse-grained molecular dynamics (CGMD) models to simulate the dynamic self-assembly of two types of amyloids (amylin and amyloid ß (Aß)). We investigate the structural and mechanical properties of different types of aggregated amyloid fibrils. Our simulations demonstrate that amyloid fibrils could result from longitudinal growth of protofilament bundles, confirming one of the hypotheses on the fibril formation. In addition, we find that the persistence length of amylin fibrils increases concurrently with their pitch length, suggesting that the bending stiffness of amylin fibrils becomes larger when the amylin fibrils are less twisted. Similar results are observed for Aß fibrils. These findings quantify the connection between the structural and the biomechanical properties of the fibrils. The CGMD models developed in this work can be potentially used to examine efficacy of anti-aggregation drugs, which could help in developing new treatments.

Electrostatic Self-Assembly of Sandwich-Like CoAl-LDH/Polypyrrole/Graphene Nanocomposites with Enhanced Capacitive Performance.

A novel sandwich-like composite with ultrathin CoAl-layered double hydroxide (LDH) nanoplates electrostatically assembled on both sides of two-dimensional polypyrrole/graphene (PG) substrate has been successfully fabricated using facile hydrothermal techniques. The PG not only serves as an excellent conductive and structural scaffold to enhance the transmission of electrons and prevent aggregation of CoAl-LDH nanoplates but also contributes to the enhancement of the specific capacitance. Owing to the homogeneous dispersion of CoAl-LDH nanoplates and its intimate interaction with PG substrate, the resulting CoAl-LDH/PG nanocomposite material exhibits excellent capacitive performance, for example, enhanced gravimetric specific capacitance (864 F g-1 at 1 A g-1 ), high rate performance (75% retention at 20 A g-1), and excellent cycle life (almost no degradation in supercapacitor performance after 5000 cycles) in aqueous KOH solution. Furthermore, the assembled asymmetric capacitor is able to deliver a superhigh energy density of 46.8 Wh kg-1 at 1.2 kW kg-1 and maintain 90.1% of its initial capacitance after 10 000 cycles. These results indicate a rational assembly strategy toward a high-performance pseudocapacitive electrode material with excellent rate performance, high specific capacitance, and outstanding cycle stability.

Functionalization of Petroleum Coke-Derived Carbon for Synergistically Enhanced Capacitive Performance.

Petroleum coke is a valuable and potential source for clean energy storage if it could be modified legitimately and facilely. In the present study, porous carbon with high surface area and abundant oxygen-containing groups was prepared from petroleum coke by chemical activation and modification processes. The as-prepared carbon exhibits a high surface area (1129 m(2) · g(-1)) and stable micrographic structure. It presents a high specific capacitance and excellent rate performance in KOH electrolyte. Even at an ultrahigh current density of 50 A · g(-1), the specific capacitance of the prepared carbon can still reach up to an unprecedented value of 261 F · g(-1) with a superhigh retention rate of 81 %. In addition, the energy density of this material in aqueous electrolyte can be as high as 13.9 Wh · kg(-1). The high energy density and excellent rate performance ensure its prosperous application in high-power energy storage system.

Ascitic fluid and serum from rats with acute pancreatitis injure rat pancreatic tissues and alter the expression of heat shock protein 60.

Acute pancreatitis (AP) is an inflammatory process in which cytokines and chemokines are involved. After onset, extrapancreatic stimuli can induce the expression of cytokines in pancreatic acinar cells, thereby amplifying this inflammatory loop. To further determine the role and mechanism of irritating agents in the pathogenesis of AP, rat pancreatic tissues were stimulated with ascitic fluid (APa) and serum (APs) from rats with AP or with lipopolysaccharide (LPS). In addition, the alteration of heat shock protein 60 (HSP60) expression was evaluated. Rat pancreas was removed and meticulously snipped to fragments. The snips were cultured for up to 48 h. During this period, the tissue viability as well as amylase and TNF-alpha levels in the supernatant and the HSP60 expression in the pancreatic tissue before and after stimulation by APa, APs, and LPS were assayed time-dependently. At different time-points during the culture, the viability and the amylase activity in the pancreatic tissue remained largely stable. After stimulation with APa, APs, or LPS for 1 h, the pancreatic tissues showed some damage, and this was followed by a sharp decrease in the viability accompanied by increased levels of amylase and TNF-alpha in the culture medium 2 or 4 h after stimulation (p < 0.05). In contrast, both the HSP60 mRNA and protein levels had a relatively high expression in the freshly prepared tissue fragments (0 h). As the culturing period was extended, the expression of HSP60 mRNA decreased only slightly; at the same time, the HSP60 protein levels decreased over a prolonged culture time, significantly so from 12 through 48 h (p < 0.05). After stimulation with APs, APa, or LPS, both the expression of HSP60 mRNA and protein in the tissue fragments increased slightly at 1 h and decreased significantly thereafter at 2 and 4 h (p < 0.05). APa, APs, or LPS induce injuries on isolated pancreatic tissues, accompanied by an altered HSP60 expression pattern in a time-dependent manner.

[Treatment of intra-articular calcaneal fractures using Kirschner's wire or calcaneal plate].

OBJECTIVE: To compare the effect and syndrome of treating intra-articular calcaneal fractures using Kirschner's wire or AO calcaneal plate. METHODS: From March 2003 to March 2006, 71 cases (86 feet) of intra-articular calcaneal fractures were treated with Kirschner's wire or AO calcaneal plate. Among them, 39 cases (48 feet) were treated using Kirschner's wire, male 34, female 5. The age ranged from 15 to 64 years old, 36 on average. The course of illness was from 4 hours to 10 days. There were 9 double side bone fractures and 30 one side bone fractures. Based on Sanders type, Type II were 40 feet, Type III were 7 feet and Type IV was 1 foot. The other 32 cases (38 feet) were treated using AO calcaneal plate, male 30, female 2. The age ranged from 18 to 55 years old, 33 on average. The course of illness was from 4 hours to 10 days. There were 6 double side bone fractures and 26 one side bone fractures. A total of 31 feet belonged to Sanders Type II, 5 to Type III, and 2 to Type IV. The 12-month follow-up, at least, was carried out in order to valuate the patients. The valuating items included: preoperative and postoperative Bohler's angle and Gissane's angle; heel bone height and width (contrast with the opposite side); to judge reposition circs by means of the CT scan and Borden's judgment; function valuation adopting the American Orthopedic Foot & Ankle Society (AOFAS) grade point system. RESULTS: Patients with Kirschner's wire fixed were followed up for 12 to 48 months, and AOFAS score ranged from 75 to 100 points, 90.6 on average. The excellent and good rate was 87.8%. The preoperative Bohler's angle was from 0 to 10 degrees, 7.8 degrees on average, and postoperative from 30 to 40 degrees, 33.2 degrees on average. The preoperation Gissane's angle was 75 to 95 degrees, 84 degrees on average; and postoperative from 115 to 135 degrees, 125 degrees on average. There was significant difference (P < 0.05). The postoperative complications were that 1 foot was the incision edge shallow putrescence and 1 foot was the needle way infection. Patients with AO calcaneal plate fixed were followed up for 12 to 48 months, and AOFAS score was from 49 to 100 points, 87.5 on average. The excellent and good rate was 81.6%. There was no significant difference between the two groups (P > 0.05). The preoperative Bohler's angle ranged from 0 to 15 degrees, 6.5 degrees on average, and postoperative from 25 to 40 degrees, 30.2 degrees on average. The preoperative Gissare's angle was 72 to 92 degrees, 80 degrees on average; and postoperative from 115 to 1300,1200 on average. There was significant difference (P < 0.05). The postoperative complications were that 5 feet were the incision edge shallow putrescence, 1 was the common peroneal nerve hurt, and 1 was the petrous muscle aponeurotic inflammation. CONCLUSION: There is no remarkable difference between the effects of treating intra-articular calcaneal fractures using plate or Kirschner's wire, but the treatment with Kirschner's wire is not only much easier and more economical, but has smaller wounds and fewer soft tissue problems.

Developing a coarse-grained force field for the diblock copolymer poly(styrene-b-butadiene) from atomistic simulation.

We have developed a coarse-grained force field for the poly(styrene-b-butadiene) diblock copolymer. We describe the computational methods and discuss how they were applied to develop a coarse-grained force field for this diblock copolymer from the atomistic simulation. The new force field contains three different bonds, four angles, five dihedral angles, and three nonbonded terms. We successfully tested this coarse-grained model against the chain properties, including static and dynamic properties, derived from the atomistic simulation; the results suggest that the coarse-grained force field is an effective model.