Search Results (49)

This study presents a novel mathematical model for bubble cavitation, demonstrating its application in the numerical simulation of steam bubble dynamics within hydrodynamic cavitation phenomena. While previous research has largely focused on the negative consequences of cavitation or its industrial applications, a key unresolved issue remains the physical mechanism of bubble destruction during collapse. This paper investigates the conditions leading to the instability of a spherical bubble’s surface, which in turn causes its irreversible collapse. The model is based on the hypothesis that a bubble is destroyed when its surface temperature exceeds a critical value (T_cr). The modified model, which accounts for heat and mass transfer processes at the bubble boundary, was used to analyse the behaviour of bubbles under different flow conditions. Our computational experiments show that the bubble collapses when the surface temperature surpasses the critical point, irrespective of its size. A comparison of theoretical and experimental data on bubble behaviour during hydrodynamic cavitation validates the proposed criterion. Specifically, the collapse of bubbles in the Venturi tube upon exceeding a critical temperature is shown, supported by experimental data with a maximum error of 6%.The results suggest that the hydraulic parameters of the flow are key factors determining the intensity of cavitation, and that the fulfillment of the condition T_s ≥ T_cr (T_cr = 647 K, p_cr = 22.5 MPa) can serve as a reliable criterion for bubble destruction. Full article

Fruit quality is crucial for nutrition and human health and requires emergent cautions in contemporary agricultural techniques. Ecological farming might not be as successful as conventional management systems; however, it may yield superior quality fruits due to reduced protection treatments. This research aimed to investigate the influence of ecological and conventional farming practices on the physicochemical properties (fruit color, weight, firmness, titratable acidity, total sugar, vitamin C), antioxidant activities, bioactive compounds (total polyphenols, anthocyanin and flavonoids), macroelements composition (N, P, K), and heavy metal concentration (Zn, Cd, Pb and Cu) of the Centenar plum variety soil system under the environmental conditions of Romania. The analysis revealed that ecological farming practice increased the total polyphenol content (3.26–4.52 mg GAE/g of dw) and antioxidant activity (19.53–21.70 µm Trolox/g of dw); however, ecological farming practice supported healthy soils and maintained or built soil organic carbon more substantially (56.68 Mg C ha⁻¹). Moreover, more consistent and vigorous fruit colors were provided by ecological farming practices where small fruits (41 g) were obtained compared to conventional farming (44 g). Among the metal content in plum fruit, Cu had the highest level (0.74–1.07 mg kg⁻¹), while Cd had the lowest (0.003–0.007 mg kg⁻¹). The potential health risk of heavy metals accumulation in orchard soils and their transfer in fruit (MTF) was also analyzed. Total carcinogenic risk (TCR) values for all metals were less than 1 (≤1), which is considered to be a safe level with no concern for human health. These results show that plum fruits under ecological farming received improved nutritional values and correspond to sustainable food production through limiting resource competition. Full article

Human core and skin temperature (T_cr and T_sk) are crucial indicators of human health and are commonly utilized in diagnosing various types of diseases. This study presents a deep learning model that combines a long-term series forecasting method with transfer learning techniques, capable of making precise, personalized predictions of T_cr and T_sk in high-temperature environments with only a small corpus of actual training data. To practically validate the model, field experiments were conducted in complex environments, and a thorough analysis of the effects of three diverse training strategies on the overall performance of the model was performed. The comparative analysis revealed that the optimized training method significantly improved prediction accuracy for forecasts extending up to 10 min into the future. Specifically, the approach of pretraining the model on in-distribution samples followed by fine-tuning markedly outperformed other methods in terms of prediction accuracy, with a prediction error for T_cr within ±0.14 °C and T_{sk, mean} within ±0.46 °C. This study provides a viable approach for the precise, real-time prediction of T_cr and T_sk, offering substantial support for advancing early warning research of human thermal health. Full article

Receptor–ligand interactions at cell interfaces initiate signaling cascades essential for cellular communication and effector functions. Specifically, T cell receptor (TCR) interactions with pathogen-derived peptides presented by the major histocompatibility complex (pMHC) molecules on antigen-presenting cells are crucial for T cell activation. The binding duration, or dwell time, of TCR–pMHC interactions correlates with downstream signaling efficacy, with strong agonists exhibiting longer lifetimes compared to weak agonists. Traditional surface plasmon resonance (SPR) methods quantify 3D affinity but lack cellular context and fail to account for factors like membrane fluctuations. In the recent years, single-molecule Förster resonance energy transfer (smFRET) has been applied to measure 2D binding kinetics of TCR–pMHC interactions in a cellular context. Here, we introduce a rigorous mathematical model based on survival analysis to determine exponentially distributed receptor–ligand interaction lifetimes, verified through simulated data. Additionally, we developed a comprehensive analysis pipeline to extract interaction lifetimes from raw microscopy images, demonstrating the model’s accuracy and robustness across multiple TCR–pMHC pairs. Our new software suite automates data processing to enhance throughput and reduce bias. This methodology provides a refined tool for investigating T cell activation mechanisms, offering insights into immune response modulation. Full article

Cholangiocarcinoma (CCA) is a rare disease characterized by malignant cells derived from the epithelial cells of the biliary duct system. Despite extensive treatments, the prognosis for CCA remains poor, emphasizing the critical need for the development of novel treatments. Considerable attention has been directed towards innate immune effector cells, which can recognize tumor cells independently of the major histocompatibility complex, laying the foundation for the development of off-the-shelf drugs. In this study, we cultured innate immune cells obtained from the peripheral blood of healthy adults and conducted a comparative analysis of the effector functions against CCA cell lines by Vδ2 γδ T cells and NK cells. This analysis was performed using standard short- and long-term cytotoxicity assays, as well as ELISA for IFN-γ. Vδ2 γδ T cells demonstrated cytotoxicity and IFN-γ production in response to CCA cells in a TCR-dependent manner, particularly in the presence of tetrakis-pivaloyloxymethyl 2-(thiazole-2-ylamino)ethylidene-1,1-bisphosphonate, a bisphosphonate prodrug. In contrast, direct killing and antibody-dependent cellular cytotoxicity were relatively slow and weak. Conversely, NK cells displayed potent, direct cytotoxicity against CCA cells. In summary, both Vδ2 γδ T cells and NK cells show promise as innate immune effector cells for adoptive transfer therapy in the context of CCA. Full article

The function of mucosal-associated invariant T (MAIT) cells, a burgeoning member of innate-like T cells abundant in humans and implicated in many diseases, remains obscure. To explore this, mice with a rearranged T cell receptor (TCR) α or β locus, specific for MAIT cells, were generated via induced pluripotent stem cells derived from MAIT cells and were designated Vα19 and Vβ8 mice, respectively. Both groups of mice expressed large numbers of MAIT cells. The MAIT cells from these mice were activated by cytokines and an agonist to produce IFN-γ and IL-17. While Vβ8 mice showed resistance in a cancer metastasis model, Vα19 mice did not. Adoptive transfer of MAIT cells from the latter into the control mice, however, recapitulated the resistance. These mice present an implication for understanding the role of MAIT cells in health and disease and in developing treatments for the plethora of diseases in which MAIT cells are implicated. Full article

The dual drive sliding feed system can obtain a uniform and stable resolution at extremely low speeds and significantly reduce the system’s nonlinear friction. However, the numerous thermal sources within the system and the multipoint sliding contact during transmission result in a significant temperature rise, leading to considerable thermal deformation and errors. Moreover, the responsive mechanism of the thermal characteristics needs to be clarified. Therefore, firstly, a frictional torque model of the engagement of the screw and nut is established, and the heat generation, heat transfer, and thermal contact resistance (TCR) are solved. Then, based on the solution, a finite element thermal simulation model of the dual drive sliding feed system is established, and experiments are performed for validation. The results show that the error in temperature at the measuring point is less than 2.1 °C, and the axial thermal elongation of the screw is less than 6.2 µm. Finally, the thermal characteristics of the feeding system under various operating conditions are analyzed. The results show that the established thermal simulated model can effectively describe the dynamic thermal characteristics of the dual drive sliding feed system during operation. The effects of the rotational speed and ambient temperature on the dynamic thermal characteristics of the dual drive sliding feed system are investigated separately. The temperature increase in each part of the screw during the operation is characterized. Full article

A significant share of allogeneic hematopoietic stem cell transplantations (allo-HSCT) results in the relapse of malignant disease. The T cell immune response to minor histocompatibility antigens (MiHAs) promotes a favorable graft-versus-leukemia response. The immunogenic MiHA HA-1 is a promising target for leukemia immunotherapy, as it is predominantly expressed in hematopoietic tissues and presented by the common HLA A*02:01 allele. Adoptive transfer of HA-1-specific modified CD8⁺ T cells could complement allo-HSCT from HA-1- donors to HA-1+ recipients. Using bioinformatic analysis and a reporter T cell line, we discovered 13 T cell receptors (TCRs) specific for HA-1. Their affinities were measured by the response of the TCR-transduced reporter cell lines to HA-1+ cells. The studied TCRs showed no cross-reactivity to the panel of donor peripheral mononuclear blood cells with 28 common HLA alleles. CD8⁺ T cells after endogenous TCR knock out and introduction of transgenic HA-1-specific TCR were able to lyse hematopoietic cells from HA-1+ patients with acute myeloid, T-, and B-cell lymphocytic leukemia (n = 15). No cytotoxic effect was observed on cells from HA-1- or HLA-A*02-negative donors (n = 10). The results support the use of HA-1 as a target for post-transplant T cell therapy. Full article

Gamma delta (γδ) T cells play a significant role in the prevention of viral infection and tumor surveillance in mammals. Although the involvement of γδ T cells in Marek’s disease virus (MDV) infection has been suggested, their detailed contribution to immunity against MDV or the progression of Marek’s disease (MD) remains unknown. In the current study, T cell receptor (TCR)γδ-activated peripheral blood mononuclear cells (PBMCs) were infused into recipient chickens and their effects were examined in the context of tumor formation by MDV and immunity against MDV. We demonstrated that the adoptive transfer of TCRγδ-activated PBMCs reduced virus replication in the lungs and tumor incidence in MDV-challenged chickens. Infusion of TCRγδ-activated PBMCs induced IFN-γ-producing γδ T cells at 10 days post-infection (dpi), and degranulation activity in circulating γδ T cell and CD8α⁺ γδ T cells at 10 and 21 dpi in MDV-challenged chickens. Additionally, the upregulation of IFN-γ and granzyme A gene expression at 10 dpi was significant in the spleen of the TCRγδ-activated PBMCs-infused and MDV-challenged group compared to the control group. Taken together, our results revealed that TCRγδ stimulation promotes the effector function of chicken γδ T cells, and these effector γδ T cells may be involved in protection against MD. Full article

The impressive clinical success of cancer immunotherapy has motivated the continued search for new targets that may serve to guide potent effector functions in an attempt to efficiently kill malignant cells. The intracellular proteome is an interesting source for such new targets, such as neo-antigens and others, with growing interest in their application for cell-based immunotherapies. These intracellular-derived targets are peptides presented by MHC class I molecules on the cell surface of malignant cells. These disease-specific class I HLA–peptide complexes can be targeted by specific TCRs or by antibodies that mimic TCR-specificity, termed TCR-like (TCRL) antibodies. Adoptive cell transfer of TCR engineered T cells and T-cell-receptor-like based CAR-T cells, targeted against a peptide-MHC of interest, are currently tested as cancer therapeutic agents in pre-clinical and clinical trials, along with soluble TCR- and TCRL-based agents, such as immunotoxins and bi-specific T cell engagers. Targeting the intracellular proteome using TCRL- and TCR-based molecules shows promising results in cancer immunotherapy, as exemplified by the success of the anti-gp100/HLA-A2 TCR-based T cell engager, recently approved by the FDA for the treatment of unresectable or metastatic uveal melanoma. This review is focused on the selection and isolation processes of TCR- and TCRL-based targeting moieties, with a spotlight on pre-clinical and clinical studies, examining peptide-MHC targeting agents in cancer immunotherapy. Full article

Ewing sarcoma (EwS) is a highly malignant sarcoma of bone and soft tissue with early metastatic spread and an age peak in early puberty. The prognosis in advanced stages is still dismal, and the long-term effects of established therapies are severe. Efficacious targeted therapies are urgently needed. Our previous work has provided preliminary safety and efficacy data utilizing T cell receptor (TCR) transgenic T cells, generated by retroviral gene transfer, targeting HLA-restricted peptides on the tumor cell derived from metastatic drivers. Here, we compared T cells engineered with either CRISPR/Cas9 or retroviral gene transfer. Firstly, we confirmed the feasibility of the orthotopic replacement of the endogenous TCR by CRISPR/Cas9 with a TCR targeting our canonical metastatic driver chondromodulin-1 (CHM1). CRISPR/Cas9-engineered T cell products specifically recognized and killed HLA-A*02:01+ EwS cell lines. The efficiency of retroviral transduction was higher compared to CRISPR/Cas9 gene editing. Both engineered T cell products specifically recognized tumor cells and elicited cytotoxicity, with CRISPR/Cas9 engineered T cells providing prolonged cytotoxic activity. In conclusion, T cells engineered with CRISPR/Cas9 could be feasible for immunotherapy of EwS and may have the advantage of more prolonged cytotoxic activity, as compared to T cells engineered with retroviral gene transfer. Full article

Aero-engine turbine stator blades are often used in harsh environments with high temperatures and high pressure and are prone to fatigue fractures. Real-time and accurate monitoring of blade surface stress and strain is critical to ensure safe operation. In this study, thin-film strain gauges (TFSGs) that can be used in high-temperature environments above 1000 °C were designed and fabricated using a PtRh6 thin film as the sensitive material. The hysteresis effect of the stress transfer upon establishing a thermo-mechanical coupling finite element model of the Inconel718 high-temperature nickel-based alloy equal-strength beam PtRh6 TFSGs was analyzed and the optimal combination of thin-film thickness and longitudinal grid length of wire-grid TFSGs was determined. In order to solve the problem of high-temperature insulation, the insulating properties of a single-layer Al₂O₃ insulating film, a single-layer ZrO₂ insulating film, a double-layer Al₂O₃/ZrO₂ composite insulating film, and a four-layer Al₂O₃/ZrO₂/Al₂O₃/ZrO₂ composite insulating film at high temperature were compared and studied using scanning electron microscopy to analyze the microscopic morphology and composition of the four insulating film structures. The results showed that the four-layer Al₂O₃/ZrO₂/Al₂O₃/ZrO₂ composite insulating film had the best insulating properties at high temperatures. On this basis, an Al₂O₃/ZrO₂/Al₂O₃/ZrO₂ composite insulating film, PtRh6 sensitive layer, and Al₂O₃ protective film were sequentially deposited on a high-temperature nickel-based alloy equal-strength beam using DC pulsed magnetron sputtering technology to obtain an Inconel718 high-temperature nickel-based alloy equal-strength beam PtRh6 TFSG. Its gauge factor (GF) and temperature coefficient of resistance (TCR) were calibrated, and the results showed that the sensor could be used in harsh environments of 1000 °C. The above results provide new ideas for measuring stress and strain in aerospace under high-temperature and high-pressure environments. Full article

T-cell-based cellular therapy was first approved in lymphoid malignancies (B-cell acute lymphoblastic leukemia and large B-cell lymphoma) and expanding its investigation and application both in hematological and non-hematological malignancies. Two anti-BCMA (B cell maturation antigen) CAR (Chimeric Antigen Receptor) T-cell therapies have been recently approved for relapsed and refractory multiple myeloma with excellent efficacy even in the heavily pre-treated patient population. This new therapeutic approach significantly changes our practice; however, there is still room for further investigation to optimize antigen receptor engineering, cell harvest/selection, treatment sequence, etc. They are also associated with unique adverse events, especially CRS (cytokine release syndrome) and ICANS (immune effector cell-associated neurotoxicity syndrome), which are not seen with other anti-myeloma therapies and require expertise for management and prevention. Other T-cell based therapies such as TCR (T Cell Receptor) engineered T-cells and non-genetically engineered adoptive T-cell transfers (Vγ9 Vδ2 T-cells and Marrow infiltrating lymphocytes) are also actively studied and worth attention. They can potentially overcome therapeutic challenges after the failure of CAR T-cell therapy through different mechanisms of action. This review aims to provide readers clinical data of T-cell-based therapies for multiple myeloma, management of unique toxicities and ongoing investigation in both clinical and pre-clinical settings. Full article

T cells are important players in the antitumor immune response. Over the past few years, the adoptive transfer of genetically modified, autologous T cells—specifically redirected toward the tumor by expressing either a T cell receptor (TCR) or a chimeric antigen receptor (CAR)—has been adopted for use in the clinic. At the moment, the therapeutic application of CD19- and, increasingly, BCMA-targeting-engineered CAR-T cells have been approved and have yielded partly impressive results in hematologic malignancies. However, employing transgenic T cells for the treatment of solid tumors remains more troublesome, and numerous hurdles within the highly immunosuppressive tumor microenvironment (TME) need to be overcome to achieve tumor control. In this review, we focused on the challenges that these therapies must face on three different levels: infiltrating the tumor, exerting efficient antitumor activity, and overcoming T cell exhaustion and dysfunction. We aimed to discuss different options to pave the way for potent transgenic T cell-mediated tumor rejection by engineering either the TME or the transgenic T cell itself, which responds to the environment. Full article

Celiac disease (CeD) manifests with autoimmune intestinal inflammation from gluten and genetic predisposition linked to human leukocyte antigen class-II (HLA-II) gene variants. Antigen-presenting cells facilitate gluten exposition through the interaction of their surface major histocompatibility complex (MHC) with the T cell receptor (TCR) on T lymphocytes. This fundamental mechanism of adaptive immunity has broadened upon recognition of extracellular exosomal MHC, raising awareness of an alternative means for antigen presentation. This study demonstrates that conditioned growth media (CGM) previously exposed to monocyte-derived dendritic cells from CeD significantly downregulates the CD3⁺ lineage marker of control T cells. Such increased activation was reflected in their elevated IL-2 secretion. Exosome localization motif identification and quantification within HLA-DQA1 and HLA-DQB1 transcripts highlighted their significant prevalence within HLA-DQB1 alleles associated with CeD susceptibility. Flow cytometry revealed the strong correlation between HLA-DQ and the CD63 exosomal marker in T cells exposed to CGM from MoDCs sourced from CeD patients. This resulted in lower concentrations of CD25⁺ CD127⁻ T cells, suggestive of their compromised induction to T-regulatory cells associated with CeD homeostasis. This foremost comparative study deciphered the genomic basis and extracellular exosomal effects of HLA transfer on T lymphocytes in the context of CeD, offering greater insight into this auto-immune disease. Full article