Search Results (87)

The cellular slime mould Dictyostelium discoideum is a soil-dwelling eukaryotic organism that undergoes distinctive morphological changes during starvation, making it a promising candidate for bioassay development. In this study, we evaluated the effects of copper (Cu) exposure on the morphological transformation of D. discoideum and performed a comparative proteomic analysis. Copper exposure on agar media delayed aggregate formation by 3.5 h compared to the controls. Approximately 280 protein spots were detected using immobilised pH gradient two-dimensional gel electrophoresis followed by silver staining. Three spots disappeared upon exposure to Cu. Based on isoelectric point and molecular weight analyses, the proteins were predicted to be formin-1, a cytoplasmic regulator of adenylyl cyclase (CRAC), and a tetratricopeptide repeat (TPR)-containing protein. Formin-1 and CRAC are involved in aggregation processes. These findings suggest that Cu disrupts aggregation-related protein expression in D. discoideum and highlight the potential of D. discoideum-based bioassays using proteomic biomarkers for environmental monitoring. Full article

Hepatocyte nuclear factor 4α (HNF4α), a highly conserved member of the nuclear receptor superfamily of transcription factors, has been identified as a promising therapeutic candidate for colorectal adenocarcinoma (CRAC). This study was to investigate the significance of HNF4α in CRAC and mechanisms governing its function. The expression patterns and clinical relevance of HNF4α were evaluated in relation to nuclear factor kappa B (NF-κb), Yes-associated protein (YAP), and epithelial–mesenchymal transition markers. HNF4α exhibited upregulation during carcinogenesis compared to normal and precancerous lesions. The overexpression and inhibition of HNF4α were correlated with the modulation of CRAC cell migration and invasion, either promoting or suppressing these processes. Notably, levels of HNF4α were significantly diminished in metastatic and poorly differentiated CRAC relative to primary CRAC samples. Moreover, reduced HNF4α levels were associated with unfavorable prognostic factors. The inhibition of HNF4A induced a decrease in NF-κb protein levels, concomitant with an increase in YAP. Our results indicate a dual role of HNF4α in tumor progression, either as a promotor or inhibitor, depending on the pathologic condition of CRAC and the related signaling pathways. HNF4α exhibits a complex role, whereby its overexpression is linked to early carcinogenesis and reduced expression is associated with the progression and metastasis of CRAC. Full article

The present study investigated the acute effects of different stretching modalities applied within a warm-up on flexibility and vertical jump height. Thirty-seven young adults participated in four randomized experimental sessions, each corresponding to a different condition: static stretch (SS), dynamic stretch (DS), contract–relax with antagonist contraction (CRAC) or a control condition with no stretch (CTRL). Conditions were five min in total duration, including 2 × 15 s stretches for each muscle group (knee flexor, knee extensor, and plantar flexor muscles). Ten min and five min of cycling preceded and followed these procedures, respectively. Hamstring flexibility and a series of countermovement jump (CMJ) measurements were interspersed within this procedure. Except for CTRL, hamstring flexibility significantly increased (p < 0.01) after all experimental procedures (7.5 ± 6.6%, 4.1 ± 4.9%, and 2.7 ± 6.0% for CRA, SS, and DS, respectively). The relative increase was significantly greater for CRAC as compared CTRL (p < 0.001). Vertical jump height significantly decreased (p < 0.05) immediately after SS (−2.3 ± 3.9%), CTRL (−2.3 ± 3.5%), and CRAC (−3.2 ± 3.3%). Jump height was unchanged after DS (0.4 ± 4.5%). Whatever the condition, no additional jump height alteration was obtained after the re-warm-up. The main findings of the present study revealed that DS is more appropriate for maintaining vertical jump height. However, stretching has no major effect when performed within a warm-up. In contrast, if the main objective is to increase flexibility, CRAC is recommended. Full article

This study addresses the issue of excessive cooling in data center server rooms caused by the sparse deployment of server cabinets. A precise air-conditioning control strategy based on the working temperature response of target cabinets is proposed. CFD software is used to establish the server room model and set control objectives. The simulations reveal that, under the condition of ensuring normal operation and equipment safety in the data center, the supply air temperature of the CRAC (computer room air conditioner) system can be adjusted to provide more flexibility, thereby reducing energy consumption. Based on this strategy, the dynamic load of the server room is simulated to obtain the supply air temperature of the CRAC system, forming a simulation dataset. A graph structure is created based on the distribution characteristics of the servers, and a regression prediction model for the supply air temperature of the CRAC system is trained using graph neural networks. The results show that, in the test set, 95.8% of the predicted supply air temperature errors are less than 0.5 °C, meeting ASHRAE standards. The model can be used to optimize the parameter settings of CRAC systems under real load conditions, reducing local hotspots in the server room while achieving energy-saving effects. Full article

High-risk neuroblastoma (HRNB) is an extracranial solid pediatric cancer. Despite the plethora of treatments available for HRNB, up to 65% of patients are refractory or exhibit an initial response to treatment that transitions to therapy-resistant relapse, which is invariably fatal. A key feature that promotes HRNB progression is aberrant calcium (Ca²⁺) signaling. Ca²⁺ signaling is regulated by several druggable channel proteins, offering tremendous therapeutic potential. Unfortunately, many of the Ca²⁺ channels in HRNB also perform fundamental functions in normal healthy cells, hence targeting them increases the potential for adverse effects. To overcome this challenge, we sought to identify novel Ca²⁺ signaling pathways that are observed in HRNB but not normal non-cancerous cells with the hypothesis that these novel pathways may serve as potential therapeutic targets. One Ca²⁺ signaling pathway that is deregulated in HRNB is store-operated Ca²⁺ entry (SOCE). SOCE relays the release of Ca²⁺ from the endoplasmic reticulum (ER) and Ca²⁺ influx via the plasma membrane and promotes cancer drug resistance by regulating transcriptional programming and the induction of mitochondrial Ca²⁺ (mtCa²⁺)-dependent signaling. mtCa²⁺ signaling is critical for cellular metabolism, reactive oxygen production, cell cycle, and proliferation and has a key role in the regulation of cell death. Therefore, a dynamic interplay between ER, SOCE, and mitochondria tightly regulates cell survival and apoptosis. From a library of synthesized novel molecules, we identified two structurally related compounds that uniquely disrupt the dynamic interplay between SOCE, ER, and mitochondrial signaling pathways and induce cell death in HRNB. Our results revealed that compounds 248 and 249 activate distinct aberrant Ca²⁺ signals that are unique to relapsed HRNB and could be exploited to induce mtCa⁺ overload, a novel calcium influx current, and subsequent cell death. These findings establish a potential new pathway of calcium-mediated cell death; targeting this pathway could be critical for the treatment of refractory and relapsed HRNB. Full article

This study investigates the potential of cement-less recycled aggregate concrete (C.R.A.C.) as an eco-friendly alternative to traditional ordinary Portland cement (OPC) concrete, using industrial waste (fly ash) and construction and demolition waste (recycled coarse aggregates). This research explores the effects of mixes of varying sodium hydroxide (NH) molarities and percentage substitutions of natural coarse aggregates (N.C.As.) with recycled coarse aggregates (R.C.As.) on the mechanical properties of C.R.A.C. A total of eighteen ambient-cured C.R.A.C. mixes, using Thar Coal fly ash with varying NH molarities (12 M, 14 M, and 16 M), and percentage substitutions of N.C.As. with R.C.As. (0%, 20%, 40%, 60%, 80%, and 100%), were prepared and tested under axial compression and flexure. It was observed that the compressive strength increased by about 76% with an increasing NH molarity, whereas the compressive strength decreased by about 52.9% with an increasing percentage substitution of N.C.As. with R.C.As. The flexural strength increased by about 78.3% with an increasing NH molarity, whereas the flexural strength decreased by about 50.5% with an increasing percentage substitution of N.C.As. with R.C.As. The SEM analysis of the C.R.A.C. mixes highlighted the heterogeneous morphology of fly ash particles (e.g., irregular shape, rough surface texture, and porous regions), which negatively influenced the overall performance of the concrete matrix. The environmental assessment exhibited that the C.R.A.C. mixes exhibited about 45% lower CO₂ emissions than OPC concrete; however, the cost of the C.R.A.C. mixes was about 21% higher than that of OPC concrete mixes. Full article

Utilizing recycled aggregates (RAs) in concrete production represents a promising path toward sustainability; however, it often results in reduced physical and durability properties. The weak interfacial transition zone (ITZ) and the adhered mortar in recycled aggregate concrete (RAC) contribute to lower mechanical strength and limit its application in demanding environments. This study investigates an accelerated carbonation technique to enhance the mechanical and durability properties of RA and RAC. Recycled aggregates, with a particle size of 10–20 mm, were subjected to carbonation at 1 bar for 2 h in a controlled carbonation chamber. Results demonstrate substantial improvements in the compressive and split tensile strengths of the carbonated recycled aggregate concrete (CRAC), with increases of 30% and 42% compared to conventional RAC, respectively. The CRAC mix also exhibited a 1.5% increase in dry density and reduced water absorption (6%) compared to RAC (7.58%). After 90 days of acid exposure, compressive strength reductions of 48.85% and 37.9% were observed for RAC and CRAC mixes, respectively, from their 28-day strength, while weight loss in CRAC was limited to 5.4%, compared to 10.92% in RAC. In sulfate exposure tests over 150 days, RAC and CRAC showed compressive strength reductions of 31.4% and 19.7% and weight losses of 3.6% and 2.2%, respectively, indicating enhanced resistance of CRAC to harsh environments. However, CRAC blended with supplementary cementitious materials (SCMs) showed diminished mechanical properties, likely due to a reduced alkaline environment caused by rapid calcium hydroxide absorption in RA pores during carbonation. Overall, the findings highlight the practical potential of accelerated carbonation to improve the performance of RAC, offering a viable pathway for sustainable construction applications. Full article

Artificial peptides P4, A1 and A4 are homologous to amphipathic α-helical fragments of the influenza virus M1 protein. P4 and A4 contain the cholesterol recognition sequence CARC, which is absent in A1. As shown previously, P4 and A4 but not A1 have cytotoxic effects on some eukaryotic and bacterial cells. This might be caused by the dysfunction of cholesterol-dependent cellular structures, inhibition of the respiratory chain, or disruption of the membrane. Here, we analyzed the latter hypothesis by studying the uncoupling effect of the peptides on asolectin membranes. The influence of A4 on Δψ pre-formed either by the valinomycin-dependent K⁺ diffusion or by the activity of membrane-built cytochrome c oxidase (CcO) was studied on (proteo)liposomes. Also, we investigated the effect of P4, A1 and A4 on liposomes loaded with calcein. It is found that A4 in a submicromolar range causes an immediate and complete dissipation of diffusion Δψ across the liposomal membrane. Uncoupling of the CcO-containing proteoliposomes requires an order of magnitude of higher peptide concentration, which may indicate the sorption of A4 on the enzyme. The presence of cholesterol in the membrane significantly weakens the uncoupling. Submicromolar A4 and P4 cause the release of calcein from liposomes, indicating the formation of membrane pores. The process develops in minutes and is significantly decelerated by cholesterol. Micromolar A1 induces pore formation in a cholesterol-independent manner. We conclude that the peptides P4, A4 and, in higher concentrations, A1 form pores in the asolectin membrane. The CARC-mediated interaction of A4 and P4 with cholesterol impedes the peptide oligomerization necessary for pore formation. The rapid uncoupling effect of A4 is apparently caused by an increase in the proton conductivity of the membrane without pore formation. Full article

The influence of the carbonation of recycled coarse aggregates on the durability performance of the recycled aggregate concrete beams is still unclear. In this study, the corrosion characteristics and flexural performance of the carbonated recycled aggregate concrete (C-RAC) beams in corrosive environments were investigated. The results illustrated that the mass loss of the longitudinal tensile steel bars (LTSBs) in the corroded C-RAC beams decreased when the replacement ratio of the carbonated recycled coarse aggregate (CRCA) increased. Compared to the corroded non-carbonated recycled aggregate concrete (NC-RAC) beam, the mass loss of LTSBs in the corroded C-RAC beam was reduced by 37.91% when the CRCA replacement ratio was 100%. The average mass loss of the short limbs of the stirrups on the tensile side of the corroded C-RAC beam was lower than that of the corroded NC-RAC beam. As the CRCA replacement ratio increased, the flexural performance of the corroded C-RAC beams was enhanced. When the CRCA replacement ratio was 100%, the ultimate load and the displacement ductility coefficient of the corroded C-RAC beam increased by 14.04% and 25.82% compared to the corroded NC-RAC beam, respectively. During the service life, the concrete strains of the cross-section at the mid-span of the corroded C-RAC beams satisfied the assumption of plane section. The research results of this study can provide some reference for the durability design and engineering application of C-RAC beams. Full article

The durability of carbonated recycled aggregate concrete (C-RAC) beams is still unclear at present. In this paper, the characteristics of corrosion-induced cracks and the steel corrosion depth of C-RAC beams were investigated through the accelerated corrosion test. The results showed that when accelerating corrosion to the 40th day, compared to the non-carbonated recycled aggregate concrete (NC-RAC) beam, the corrosion-induced cracking area of the C-RAC beam with a 100% carbonated recycled coarse aggregate (C-RCA) replacement ratio decreased by 40.00%, while the total length of the corrosion-induced cracks (CCs) increased by 51.82%. The type of probability distribution for the width of the CCs on the tension side of the C-RAC beams was a lognormal distribution. Compared with the NC-RAC beam, the mean value of the width of the CCs of the C-RAC beam with a 100% C-RCA replacement ratio decreased by 66.67%, the crack width distribution was more concentrated, and the quartiles and median were all reduced. With an increase in the C-RCA replacement ratio, the fractal dimension and the scale coefficient of CCs on the tension side of the beams showed an approximate trend of first increasing and then decreasing. The distribution of the corrosion depth of longitudinal tensile steel bars in the C-RAC beams was a mainly normal distribution. When the C-RCA replacement ratio increased from 30% to 100%, the mean value of the corrosion depth of the longitudinal tensile steel bars decreased by 33.46%, and the trend of changes in the quartiles and medians was basically the same as the trend of changes in the mean value. The research results can provide some reference for promoting the engineering application of C-RAC beams. Full article

Ion channels of T cells (Kv1.3, KCa3.1, and CRAC) participate in the regulation of activation and effector functions via modulation of the Ca²⁺-dependent pathway. T cells expressing chimeric antigen receptors (CAR T cells) showed a remarkable role in anti-tumor therapy, especially in the treatment of chemotherapy-resistant liquid cancers. Nevertheless, many challenges remain to be overcome to improve the treatment for solid tumors. In this study, we assessed the expression and role of ion channels in CAR T cells. We found that HER2-specific CAR T cells had higher KCa3.1 conductance compared to the non-transduced (NT, control) cells, which was more prominent in the CD8⁺ population (CD4⁺ cell also showed elevation). Conversely, the Kv1.3 expression level was the same for all cell types (CD4⁺, CD8⁺, CAR, and NT). Single-cell Ca²⁺ imaging revealed that thapsigargin-induced SOCE via CRAC is suppressed in CD8⁺ CAR T cells, unlike for CD4⁺ and CD8⁺ NT cells. To dissect the functional role of Kv1.3 and KCa3.1, we used specific antagonists (Kv1.3: Vm24; KCa3.1: TRAM-34): the target cell elimination capacity of the CD8⁺ CAR T cells was improved either by blocking KCa3.1 or Kv1.3. These results imply that ion channels could be a target in CAR T cell immunotherapy elaboration. Full article

Gene therapy is the technique of inserting foreign genetic elements into host cells to achieve a therapeutic effect. Although gene therapy was initially formulated as a potential remedy for specific genetic problems, it currently offers solutions for many diseases with varying inheritance patterns and acquired diseases. There are two major groups of vectors for gene therapy: viral vector gene therapy and non-viral vector gene therapy. This review examines the role of a macromolecule’s chemical and physical architecture in non-viral gene delivery, including their design and synthesis. Polymers can boost circulation, improve delivery, and control cargo release through various methods. The prominent examples discussed include poly-L-lysine, polyethyleneimine, comb polymers, brush polymers, and star polymers, as well as hydrogels and natural polymers and their modifications. While significant progress has been made, challenges still exist in gene stabilization, targeting specificity, and cellular uptake. Overcoming cytotoxicity, improving delivery efficiency, and utilizing natural polymers and hybrid systems are vital factors for prospects. This comprehensive review provides an illuminating overview of the field, guiding the way toward innovative non-viral-based gene delivery solutions. Full article

Atopic dermatitis (AD) is a common allergic inflammatory skin condition marked by severe itching, skin lichenification, and chronic inflammation. AD results from a complex immune response, primarily driven by T lymphocytes and environmental triggers, leading to a disrupted epidermal barrier function. Traditional treatments, such as topical corticosteroids, have limitations due to long-term side effects, highlighting the need for safer alternatives. Here, we aimed to show that Agrimonia coreana extract (AC_ext) can be used in treating AD-related dermatologic symptoms. AC_ext could inhibit CRAC (Calcium Release-Activated Calcium) channel activity, reducing Orai1/CRAC currents and decreasing intracellular calcium signaling. This inhibition was further confirmed by the reduced IL-2 levels and T cell proliferation upon AC_ext treatment. In a mouse model of AD, AC_ext significantly ameliorates symptoms, improves histological parameters, and enhances skin barrier function, demonstrating its potential for treating AD. Full article

The rise in greenhouse gases, particularly carbon dioxide (CO₂) emissions, in the atmosphere is one of the major causes of global warming and climate change. The production of ordinary Portland cement (OPC) emits harmful CO₂ gases, which contribute to sporadic heatwaves, rapid melting of glaciers, flash flooding, and food shortages. To address global warming and climate change challenges, this research study explores the use of a cement-less recycled aggregate concrete, a sustainable approach for future constructions. This study uses fly ash, an industrial waste of coal power plants, as a 100% substitute for OPC. Moreover, this research study also uses recycled coarse aggregates (RCAs) as a partial to complete replacement for natural coarse aggregates (NCAs) to preserve natural resources for future generations. In this research investigation, a total of 60 pull-out specimens were prepared to investigate the influence of steel bar diameter (9.5 mm, 12.7 mm, and 19.1 mm), bar embedment length, $d_b$ (4$d_b$ and 6$d_b$), and percentage replacements of NCA with RCA (25%, 50%, 75%, and 100%) on the bond stress behavior of cement-less RA concrete. The test results exhibited that the bond stress of cement-less RCA concrete decreased by 6% with increasing steel bar diameter. Moreover, the bond stress decreased by 5.5% with increasing bar embedment length. Furthermore, the bond stress decreased by 7.6%, 7%, 8.8%, and 20.4%, respectively, with increasing percentage replacements (25%, 50%, 75%, and 100%) of NCA with RCA. An empirical model was developed correlating the bond strength to the mean compressive strength of cement-less RCA concrete, which matched well with the experimental test results and predictions of the CEB-FIP model for OPC. The CRAC mixes exhibited higher costs but significantly lower embodied CO₂ emissions than OPC concrete. Full article

Hydraulic fracturing is vital in recovering hydrocarbons from oil and gas reservoirs. It involves injecting a fluid under high pressure into reservoir rock. A significant part of fracturing fluids is the addition of polymers that become gels or gel-like under reservoir conditions. Polymers are employed as viscosifiers and friction reducers to provide proppants in fracturing fluids as a transport medium. There are numerous systems for fracturing fluids based on macromolecules. The employment of natural and man-made linear polymers, and also, to a lesser extent, synthetic hyperbranched polymers, as additives in fracturing fluids in the past one to two decades has shown great promise in enhancing the stability of fracturing fluids under various challenging reservoir conditions. Modern innovations demonstrate the importance of developing chemical structures and properties to improve performance. Key challenges include maintaining viscosity under reservoir conditions and achieving suitable shear-thinning behavior. The physical architecture of macromolecules and novel crosslinking processes are essential in addressing these issues. The effect of macromolecule interactions on reservoir conditions is very critical in regard to efficient fluid qualities and successful fracturing operations. In future, there is the potential for ongoing studies to produce specialized macromolecular solutions for increased efficiency and sustainability in oil and gas applications. Full article