Search Results (53,416)

Chimeric antigen receptor (CAR) T-cell therapy has been proven to be an effective strategy for the treatment of hematological malignancies. At present, how to prepare CAR-T cells efficiently, quickly, and safely is one of the urgent problems to be solved. The durability and activity of engineered T cells in solid tumors need to be further improved, and the strategy of T cells penetrating the tumor microenvironment also needs to be improved. In addition, although the problems mainly caused by T-cell biology are being solved, the manufacturing mode and process still need to be improved to ensure that CAR-T cell therapy can be widely used. This paper summarizes some strategies that can improve the efficacy of CAR-T cells. Full article

In this study, we proposed a fast and accurate PatchMixer-based framework (Patch-TS). After the data were processed, which included missing values and normalization, the environmental factors were selected via the Pearson correlation coefficient method. Then, the newly developed sap flow prediction model was trained. The resulting data demonstrated that the coefficient of determination (R²), mean squared error (MSE), and mean absolute error (MAE) are 0.921, 0.00824, and 0.0497, respectively. The R² of Patch-TS further improved to 0.929 after 7 factors were extracted via the Pearson correlation method. Furthermore, we comparatively analyse the mitigating effects of RevIn (Reversible Instance Normalization) and Dish-TS on data drift. In addition to the predictive performance of the models under different prediction windows, Patch-TS outperforms the other models. The results demonstrate that the model developed in this paper is an effective tool for accurately predicting sap flow, which is a valuable contribution to the practical management of trees and forests. Full article

Background/Objectives: This paper deals with quality of life (QoL), mental well-being (WB), anxiousness, and stress vulnerability in women with tetany syndrome (TS) in comparison with the population without the syndrome. The aim is to investigate the individual or combined effects of anxiousness, stress vulnerability, and tetany syndrome diagnosis on quality of life and well-being in women. Methods: The research sample was composed of 144 female (in terms of sex) respondents with a diagnosis of tetany syndrome and 123 females without the syndrome (comparative group). The questionnaire battery was used for data collection (WHOQoL-BREF, Warwick–Edinburgh mental well-being scale, STAI (X-2), and Stress Vulnerability Scale). In processing, comparisons, correlations, and MANCOVA analyses were used. Results: The group with tetany syndrome showed significantly lower levels of quality of life (all domains) and well-being and significantly higher anxiousness compared to the group without the syndrome. In vulnerability to stress, a significant difference between groups was not shown. Multivariate testing showed a small interaction effect of tetany syndrome, anxiousness, and stress vulnerability on well-being and quality of life, while anxiousness still had the largest independent effect. Conclusions: Lifestyle aspects seem to be a possible intervening factor that, in interaction with anxiety, contributes to a worse quality of life and well-being in individuals with tetany syndrome. The results contribute to the perception of psychological intervention, in terms of stress management and support for a healthy lifestyle, as important in addition to mineral supplementation or medication treatment. Full article

Microtubule-actin cross-linking factor 1 (MACF1), also known as actin cross-linking family protein 7 (ACF7), is a giant cytolinker protein with multiple conserved domains that can orchestrate cytoskeletal networks of actin and microtubules. MACF1 is involved in various biological processes, including cell polarity, cell–cell connection, cell proliferation, migration, vesicle transport, signal transduction, and neuronal development. In this review, we updated the physiological and pathological roles of MACF1, highlighting the components and signaling pathways involved. Novel evidence showed that MACF1 is involved in diverse human diseases, including multiple neuronal diseases, congenital myasthenic syndrome, premature ovarian insufficiency, spectraplakinopathy, osteoporosis, proliferative diabetic retinopathy, and various types of cancer. We also reviewed the physiological roles of MACF1, including its involvement in adhesome formation, bone formation, neuronal aging, and tooth development. In addition, MACF1 plays other roles, functioning as a biomarker for the prediction of infections in patients with burns and as a marker for genome selection breeding. These studies reinforce the idea that MACF1 is a bona fide versatile, multifaceted giant protein. Identifying additional MACF1 functions would finally help with the treatment of diseases caused by MACF1 defects. Full article

Temperature is a key environmental factor that influences mosquito phenotypic traits and the effectiveness of vector control strategies. Bacillus velezensis (Bv) has shown promise as a microbial biocontrol agent due to its insecticidal properties; however, its effects on mosquitoes under different environmental conditions are still unexplored. This study investigated the effects of Bv (strain WHk23) exposure on the life history traits of Culex quinquefasciatus at two temperature conditions (20 °C and 30 °C), focusing on development, longevity, and reproductive fitness. Results showed that temperature significantly affected mosquito development and longevity, with faster development and shorter adult longevity observed at 30 °C compared to 20 °C. Exposure to Bv further accelerated larval development and reduced adult emergence, with the effects being more pronounced at 30 °C than at 20 °C. Exposure to Bv reduced adult longevity regardless of temperature. In addition, Bv-exposed females had larger body sizes but lower fecundity and fertility, suggesting that Bv exposure may cause physiological stress that disrupts reproductive processes. These findings highlight the importance of considering environmental factors in mosquito control programs while reinforcing the efficacy of Bv as a sustainable biocontrol agent under a variety of environmental conditions. Full article

Diabetic retinopathy (DR) is a significant microvascular consequence of diabetes mellitus (DM), resulting in visual impairment and blindness. Controlling hyperglycemia is essential for avoiding and alleviating diabetic retinopathy. Nutrients and natural compounds possessing hypoglycemic characteristics present promising supplementary approaches to conventional therapies. This review assesses the influence of nutrients and natural substances on glycemic regulation and their possible effects on diabetic retinopathy. Goal: To investigate and consolidate knowledge about nutrients and natural compounds exhibiting hypoglycemic properties and their processes in the prevention and management of diabetic retinopathy. Approaches: Extensive reviews were conducted on pertinent studies from databases including PubMed, Scopus, and Web of Science. Selection criteria encompassed papers that examined natural substances, nutrients, or dietary supplements exhibiting effects on blood glucose levels and pathways associated to diabetic retinopathy. Principal findings were encapsulated according to their mechanisms, efficacy, and safety. Outcomes: Numerous foods, including omega-3 fatty acids, vitamin D, and polyphenols (e.g., curcumin, resveratrol), have hypoglycemic properties by improving insulin sensitivity and diminishing oxidative stress. Natural substances like berberine, quercetin, and flavonoids demonstrate analogous effects, influencing pathways associated with inflammation, advanced glycation end products (AGEs), and angiogenesis, which are critical factors in the evolution of diabetic retinopathy (DR). The synergistic benefits of integrating natural medicines with conventional antidiabetic medications may enhance glycemic control and reduce retinal damage. The safety profiles of these therapies are predominantly positive; nonetheless, clinical trials are still constrained in both breadth and scale. Conclusions: Nutrients and natural compounds are promising supplementary approaches for glycemic regulation and the therapy of diabetic retinopathy. Additional research, encompassing extensive clinical studies, is required to substantiate their efficacy, determine optimal dose, and verify long-term safety. The use of these natural substances into clinical practice may improve comprehensive management of diabetes and associated consequences. Full article

In this study, an adaptive impact-time-control cooperative guidance law based on deep reinforcement learning considering field-of-view (FOV) constraints is proposed for high-speed UAVs with time-varying velocity. Firstly, a reinforcement learning framework for the high-speed UAVs’ guidance problem is established. The optimization objective is to maximize the impact velocity; and the constraints for impact time, dive attacking, and FOV are considered simultaneously. The time-to-go estimation method is improved so that it can be applied to high-speed UAVs with time-varying velocity. Then, in order to improve the applicability and robustness of the agent, environmental uncertainties, including aerodynamic parameter errors, observation noise, and target random maneuvers, are incorporated into the training process. Furthermore, inspired by the RL${}^2$ algorithm, the recurrent layer is introduced into both the policy and value network. In this way, the agent can automatically adapt to different mission scenarios by updating the hidden states of the recurrent layer. In addition, a compound reward function is designed to train the agent to satisfy the requirements of impact-time control and dive attack simultaneously. Finally, the effectiveness and robustness of the proposed guidance law are validated through numerical simulations conducted across a wide range of scenarios. Full article

Real-time parametric interpolation plays a crucial role in achieving high-speed and high-precision multi-axis CNC machining. In the interpolation cycle, the position of the next interpolation point is required to be calculated in real-time to guide the action of the machining process. Due to the existence of the positioning error of the interpolation point, it is extremely difficult to eliminate the feedrate fluctuation, which may lead to dramatic decreases in machining quality and the driving capabilities’ saturation of each axis. A computationally efficient and precise feedrate fluctuation minimization method is proposed for the NURBS tool path interpolation in the CNC milling process. The model for the arc length and curvature, with respect to the parameter of the NURBS tool path, is established to reduce the calculation amount required by interpolation points determination. The deviation between the theoretical and actual interpolation step length is decreased by the proposed arc length compensation method to minimize the feedrate fluctuation. In addition, the interpolation points derived from the arc length compensation process are further corrected by performing the Newton iteration to restrict the feedrate fluctuation within the preset accuracy threshold. The effectiveness and superiorities of the proposed feedrate fluctuation minimization method are verified by simulation and milling experiments. Full article

According to recent global public health studies, chronic kidney disease (CKD) is becoming more and more recognized as a serious health risk as many people are suffering from this disease. Machine learning techniques have demonstrated high efficiency in identifying CKD, but their opaque decision-making processes limit their adoption in clinical settings. To address this, this study employs a generative adversarial network (GAN) to handle missing values in CKD datasets and utilizes few-shot learning techniques, such as prototypical networks and model-agnostic meta-learning (MAML), combined with explainable machine learning to predict CKD. Additionally, traditional machine learning models, including support vector machines (SVM), logistic regression (LR), decision trees (DT), random forests (RF), and voting ensemble learning (VEL), are applied for comparison. To unravel the “black box” nature of machine learning predictions, various techniques of explainable AI, such as SHapley Additive exPlanations (SHAP) and local interpretable model-agnostic explanations (LIME), are applied to understand the predictions made by the model, thereby contributing to the decision-making process and identifying significant parameters in the diagnosis of CKD. Model performance is evaluated using predefined metrics, and the results indicate that few-shot learning models integrated with GANs significantly outperform traditional machine learning techniques. Prototypical networks with GANs achieve the highest accuracy of 99.99%, while MAML reaches 99.92%. Furthermore, prototypical networks attain F1-score, recall, precision, and Matthews correlation coefficient (MCC) values of 99.89%, 99.9%, 99.9%, and 100%, respectively, on the raw dataset. As a result, the experimental results clearly demonstrate the effectiveness of the suggested method, offering a reliable and trustworthy model to classify CKD. This framework supports the objectives of the Medical Internet of Things (MIoT) by enhancing smart medical applications and services, enabling accurate prediction and detection of CKD, and facilitating optimal medical decision making. Full article

This study explored the enhancement of antioxidant properties in bread by incorporating ginger powder while reducing wheat flour utilisation through partial replacement with cassava flour, addressing the issue that bread produced from refined wheat flour is low in antioxidants due to the removal of the aleurone layer during processing. The study investigated the effect of cassava flour and ginger powder addition on physicochemical properties (moisture content, water activity, firmness, crumb structure, density, volume, specific volume, and colour), antioxidant capacity (AC) using Ferric reducing antioxidant potential (FRAP), and total phenolic content (TPC) (by using the Folin Ciocalteu method) of bread. Seven bread samples were produced using the Chorleywood method (220 ± 1 °C at 25 min) using cassava flour (10 and 40%) only and with the combination of ginger powder (1 and 3%). The volume, specific volume, and firmness of the bread with 10% cassava flour and ginger powder were similar to the control (100% wheat flour). Breads containing 40% cassava flour had reduced volume and specific volume and increased firmness and density. The TPC and AC increased significantly (p < 0.05) with ginger powder addition. The study showed that 10% cassava flour and 3% ginger powder could be added to bread formulations to improve their phenolic content and antioxidant capacity without significantly affecting their quality. Full article

Directed Energy Deposition-Laser Beam (DED-LB) is an ideal Additive Manufacturing (AM) process to obtain very complex geometries, which can be important for several applications in industries such as aerospace and biomedical engineering. The present study aims to determine optimized DED-LB parameters for printing 17-7 PH stainless steel, a semi-austenitic precipitation-hardening alloy renowned for its exceptional combination of high yield strength, toughness, and corrosion resistance. The experimental work used different combinations of laser power, scanning speed, and powder feed rate to investigate the effects on the morphology, surface roughness, and microstructure of the deposited material. The results indicated that a powder feed rate of 4.7 g/min yielded uniform beads, reduced surface roughness, and increased substrate dilution, enhancing the metallurgical bond between the bead and substrate. Conversely, higher feed rates, such as a rate of 9.2 g/min, resulted in increased surface irregularities due to an excessive amount of partially melted powder particles. Microstructural analysis, supported by thermodynamic calculations, confirmed a ferritic–austenitic solidification mode. The austenite and ferrite fractions varied significantly, depending mainly on the substrate dilution due to the decrease in aluminum content. The combination of 400 W laser power and a 2000 mm/min scanning speed resulted in the optimal set of parameters, with an approximately 30% dilution and 80% austenite. Full article

The increasing use of computed tomography (CT) has led to a rise in cumulative radiation dose due to medical imaging, raising concerns about potential long-term adverse effects. Large-scale epidemiological studies indicate a higher tumor incidence associated with CT examinations, but the underlying biological mechanisms remain largely unexplained. To gain further insights into the cellular response triggered by routine CT diagnostics, we investigated CT-induced changes of gene expression in peripheral blood cells using whole transcriptome sequencing. RNA was isolated from peripheral blood cells of 40 male patients with asymptomatic microhematuria, sampled before and after multi-phase abdominal CT (CTDIvol: 3.75–26.95 mGy, median: 6.55 mGy). On average, 22.11 million sequence reads (SD 5.71) per sample were generated to identify differentially expressed genes 6 h post-exposure by means of DESeq2. To assess the dose dependency of CT-induced effects, we additionally divided samples into three categories: low exposure (≤6.55 mGy, n = 20), medium exposure (>6.55 mGy and <12 mGy, n = 16), and high exposure (≥12 mGy, n = 4), and repeated gene expression analysis for each subset and their corresponding prae-exposure sample. CT exposure caused consistent and dose-dependent upregulation of six genes (EDA2R, AEN, FDXR, DDB2, PHLDA3, and MIR34AHG; padj < 0.1). These genes share several functional commonalities, including regulation by TP53 and involvement in the DNA damage response. The biological pathways highlighted by Gene Set Enrichment Analysis (GSEA) suggest a dose-dependent increase of cellular damage and metabolic particularities in the low-exposure subset, which may be related to a potential adaptive cellular response to low-dose irradiation. Irrespective of applied dose, AEN emerged as the most robust biomarker for CT exposure among all genes. Routine abdominal CT scans cause dose-dependent gene deregulation in association with DNA damage in peripheral blood cells after in vivo exposure. Regarding risk assessment of CT, our results support the commonly applied “As Low–As –Reasonably Achievable (ALARA)” principle. Evidence of additional gene expression changes associated with metabolic processes indicates a rather complex molecular response beyond DNA damage after CT exposure, and emphasizes the need for further targeted investigations. Full article

Si₃N₄ ceramics and composites stand out for their exceptional mechanical and thermal properties. Compared with conventional ceramic forming processes, 3D printing via vat photopolymerization not only ensures high geometric precision but also improves the forming efficiency and strength of green body. Nevertheless, the grayish appearance of Si₃N₄ and its relatively high refractive index can adversely affect the photocuring behavior in ceramic slurries. The primary objectives focus on enhancing the curing performance and rheological properties of slurries, minimizing defects during post-processing, and improving the relative density and mechanical properties of Si₃N₄ ceramics. Key advancements include slurry optimization via refractive index matching, biomodal particle gradation and surface modification, while the integration of whisker/fiber additions or polymer-derived ceramic strategies enhances mechanical properties. In addition, controlling the atmosphere and heating rate of the post-processing innovations can achieve a relative density of more than 95%. This paper introduces the mechanisms of vat photopolymerization and then summarizes the strategies for improving Si₃N₄ ceramic slurries as well as controlling the printing and debinding/sintering processes. It further highlights the ways in which different approaches can be used to enhance the properties of Si₃N₄ slurries and ceramic parts. Finally, applications of Si₃N₄ ceramics and composites via vat photopolymerization in various fields such as aviation, aerospace, energy, electronics, chemical processes, and biomedical implants are also presented to point out future opportunities and challenges. Full article

This study investigates the potential of Spirulina biomass as a lubricating additive for drilling fluid formulations. In this work, this waste protein is evaluated as a lubricant alternative that may decrease the coefficient of friction while improving the rheological profiles and/or reducing fluid loss via permeation in drilling fluids. A processed and dried Arthrospira platensis (Spirulina) biomass is incorporated into drilling fluid formulations and compared to standard lubricant additives for the drilling fluid properties of lubricity, rheology, and fluid loss. Rheological characterization includes the determination of yield stress, gel strength, and viscosity measurements. The major findings of this study include a friction value reduction of up to 30% and a fluid loss reduction of up to 51% by using 3 vol.% Spirulina. Parameters were fit to two rheological models (Bingham plastic and Herschel–Bulkley). After experimentation and analyzing the data gathered, it was determined that Spirulina and the Spirulina–Coastalube mixture in drilling fluids are good potential candidates as more environmentally benign and cost-effective alternative technologies for drilling fluids for decreasing the coefficient of friction, which results in increasing the lubrication performance of the drilling fluids. Full article

In milk, casein proteins orientate themselves into spherical micellar structures with hydrophobic casein subtypes concentrated in the core, while hydrophilic casein subtypes populate the exterior. Previous research demonstrated that milk with the addition of emulsifying salts coupled with high-pressure homogenization induced an unprecedented amount of casein micelle dissociation. This research aims to quantify the extent of casein micelle dissociation in diluted skim milk and evaluate the functionality of these proteins following emulsifying salt treatment coupled with high-pressure homogenization. To evaluate the extent of micellar dissociation, dilute skim milk solutions (20% v/v) were prepared with a varying amount of treatment: no processing (control), just emulsifying salts (Treatment E, 100 mM sodium hexametaphosphate), just high-pressure homogenization (Treatment H, at 300 MPa), and EH (a combination of E and H treatments). Samples were then put through varying filter sizes (0.22 µm, 0.05 µm), and the permeates were analyzed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In the control group (20% skim milk), 9.35% ± 2.53% casein protein permeated through a 0.05 µm filter. Alternatively, 93.2% ± 7.71% casein protein was present in EH samples post-filtration through a 0.05 µm filter, demonstrating a significant processing-induced dissociation of casein micelles. A potential benefit to this casein micelle size reduction is the exposure of highly functional hydrophobic subunits from the core of the micelle. In agreement, compared to the control samples, the EH samples had higher foam expansion index values (138.3% ± 12.58% vs. 33.33% ± 14.43% at 0 h), foam stability (113.3% ± 5.774% vs. 21.67% ± 2.887% after 8 h), emulsifying activity (ca. two-fold higher), and interaction with caffeine. These data demonstrate that E, coupled with H, enhances skim milk system functionality, and these changes are likely due to micellar dissociation and protein conformational changes. This work has direct applications in dairy systems (e.g., dairy foams, dairy ingredients) as well as implications for potential processing strategies for other protein-rich systems. Full article