Treatment of multiple myeloma: What is the impact on T-cell function?

Treatment of multiple myeloma (MM) has evolved remarkably over the past few decades. Autologous stem cell transplantation, as well as proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies, has substantially improved the prognosis of patients with MM. Novel therapies, including chimeric antigen receptor-T cells, bispecific T-cell engagers, antibody-drug conjugates, histone deacetylase inhibitors, and nuclear export inhibitors, have provided more options. However, MM remains incurable. T cells are the principal weapons of antitumor immunity, but T cells display a broad spectrum of dysfunctional states during MM. The promising clinical results of T-cell-directed immunotherapies emphasize the significance of enhancing T-cell function in antimyeloma treatment. This review summarizes the potential effects of these antimyeloma agents on T-cell function and discusses possible optimized strategies for MM management by boosting T-cell immunity.

Preparation of Ceramic Fiber Threads with Enhanced Abrasion Resistance Performance.

Ceramic fiber thread is one of the key components in flexible external thermal insulation blankets, and it has been applied in various fields as a flexible ceramic fibrous material with excellent deformability and high-temperature resistance. However, ceramic fiber threads are often subjected to reciprocating friction motion at specific bending angles, making them highly susceptible to abrade and fracture. Enhancing the abrasion resistance performance of ceramic fiber threads under bending conditions is the future trend and remains a significant challenge. Hence, we design and construct a novel polyurethane-modified coating on the ceramic fiber threads to improve their abrasion resistance performance. The effects of the types and concentrations of modifiers on the microstructure, abrasion resistance property, and tensile property of ceramic fiber threads are systematically investigated. The ceramic fiber threads, after modification with hexamethylene diisocyanate waterborne polyurethane (HDI-WPU) with a concentration of 3%, exhibit excellent abrasion resistance properties. The number of friction cycles at fracture of the modified ceramic fiber thread is more than three times, and the tensile strength is more than one and a half times, that of the original ceramic fiber thread, demonstrating the great potential of the HDI-WPU modifier for enhancing the abrasion resistance performance of ceramic fiber threads.

Triterpene esters of cirsium setosum and their anti-inflammatory activity.

Two new triterpene fatty acid esters, 3ß-palmityloxy-12,27-cyclofriedoolean-14-en-11α-ol (1) and 3ß-palmityloxy-19α-hydroxyursane (2), together with 3ß-hydroxy-11-oxo-olean-12-enyl palmitate (3) were isolated from the potent anti-inflammatory active fraction of the petroleum ether-soluble part of Cirsium setosum ethanol extract. Compound 1 was found to be a rare 12,27-cyclopropane triterpenoid. Their structures were determined through spectral data analysis combined with literature reports. Furthermore, in vitro experiment, compounds 1-3 exhibited significant inhibitory effects on nitric oxide production in lipopolysaccharide-activated mouse RAW264.7 macrophages.

Structural elucidation and complete NMR spectral assignments of Monascus monacolin analogues.

Three new monacolin analogues, 3,6-dihydroxy-monacolin P (1), 6-methoxy monacolin S (2), and 6-methoxy dehydromonacolin S (3), were isolated from a fraction that strongly inhibited 3-hydroxy-3-methylglutaryl-CoA reductase from the ethyl acetate portion of red yeast rice ethanol extract. Their structures were determined through a combination of 1D and 2D NMR experiments, mass spectrometry analysis, and known literature reports.

GHITM regulates malignant phenotype and sensitivity to PD-1 blockade of renal cancer cells via Notch signalling.

Growth hormone inducible transmembrane protein (GHITM), one member of Bax inhibitory protein-like family, has been rarely studied, and the clinical importance and biological functions of GHITM in kidney renal clear cell carcinoma (KIRC) still remain unknown. In the present study, we found that GHITM was downregulated in KIRC. Aberrant GHITM downregulation related to clinicopathological feature and unfavourable prognosis of KIRC patients. GHITM overexpression inhibited KIRC cell proliferation, migration and invasion in vitro and in vivo. Mechanistically, GHITM overexpression could induce the downregulation of Notch1, which acts as an oncogene in KIRC. Overexpression of Notch1 effectively rescued the inhibitory effect induced by GHITM upregulation. More importantly, GHITM could regulate PD-L1 protein abundance and ectopic overexpression of GHITM enhanced the antitumour efficiency of PD-1 blockade in KIRC, which provided new insights into antitumour therapy. Furthermore, we also showed that YY1 could decrease GHITM level via binding to its promoter. Taken together, our study revealed that GHITM was a promising therapeutic target for KIRC, which could modulate malignant phenotype and sensitivity to PD-1 blockade of renal cancer cells via Notch signalling pathway.

NRhFluors: Quantitative Revealing the Interaction between Protein Homeostasis and Mitochondria Dysfunction via Fluorescence Lifetime Imaging.

Degenerative diseases are closely related to the changes of protein conformation beyond the steady state. The development of feasible tools for quantitative detection of changes in the cellular environment is crucial for investigating the process of protein conformational variations. Here, we have developed a near-infrared AIE probe based on the rhodamine fluorophore, which exhibits dual responses of fluorescence intensity and lifetime to local viscosity changes. Notably, computational analysis reveals that NRhFluors fluorescence activation is due to inhibition of the RACI mechanism in viscous environment. In the chemical regulation of rhodamine fluorophores, we found that variations of electron density distribution can effectively regulate CI states and achieve fluorescence sensitivity of NRhFluors. In addition, combined with the AggTag method, the lifetime of probe A9-Halo exhibits a positive correlation with viscosity changes. This analytical capacity allows us to quantitatively monitor protein conformational changes using fluorescence lifetime imaging (FLIM) and demonstrate that mitochondrial dysfunction leads to reduced protein expression in HEK293 cells. In summary, this work developed a set of near-infrared AIE probes activated by the RACI mechanism, which can quantitatively detect cell viscosity and protein aggregation formation, providing a versatile tool for exploring disease-related biological processes and therapeutic approaches.

Hydrologic cycle weakening in hothouse climates.

The hydrologic cycle has wide impacts on the ocean salinity and circulation, carbon and nitrogen cycles, and the ecosystem. Under anthropogenic global warming, previous studies showed that the intensification of the hydrologic cycle is a robust feature. Whether this trend persists in hothouse climates, however, is unknown. Here, we show in climate models that mean precipitation first increases with rising surface temperature, but the precipitation trend reverses when the surface is hotter than ~320 to 330 kelvin. This nonmonotonic phenomenon is robust to the cause of warming, convection scheme, ocean dynamics, atmospheric mass, planetary rotation, gravity, and stellar spectrum. The weakening occurs because of the existence of an upper limitation of outgoing longwave emission and the continuously increasing shortwave absorption by H2O and is consistent with atmospheric dynamics featuring the strong increase of atmospheric stratification and marked reduction of convective mass flux. These results have wide implications for the climate evolutions of Earth, Venus, and potentially habitable exoplanets.

Hybrid transformer convolutional neural network-based radiomics models for osteoporosis screening in routine CT.

OBJECTIVE: Early diagnosis of osteoporosis is crucial to prevent osteoporotic vertebral fracture and complications of spine surgery. We aimed to conduct a hybrid transformer convolutional neural network (HTCNN)-based radiomics model for osteoporosis screening in routine CT. METHODS: To investigate the HTCNN algorithm for vertebrae and trabecular segmentation, 92 training subjects and 45 test subjects were employed. Furthermore, we included 283 vertebral bodies and randomly divided them into the training cohort (n = 204) and test cohort (n = 79) for radiomics analysis. Area receiver operating characteristic curves (AUCs) and decision curve analysis (DCA) were applied to compare the performance and clinical value between radiomics models and Hounsfield Unit (HU) values to detect dual-energy X-ray absorptiometry (DXA) based osteoporosis. RESULTS: HTCNN algorithm revealed high precision for the segmentation of the vertebral body and trabecular compartment. In test sets, the mean dice scores reach 0.968 and 0.961. 12 features from the trabecular compartment and 15 features from the entire vertebral body were used to calculate the radiomics score (rad score). Compared with HU values and trabecular rad-score, the vertebrae rad-score suggested the best efficacy for osteoporosis and non-osteoporosis discrimination (training group: AUC = 0.95, 95%CI 0.91-0.99; test group: AUC = 0.97, 95%CI 0.93-1.00) and the differences were significant in test group according to the DeLong test (p < 0.05). CONCLUSIONS: This retrospective study demonstrated the superiority of the HTCNN-based vertebrae radiomics model for osteoporosis discrimination in routine CT.

Light pulse storage in Pr:YSO crystal based on the revival of silenced echo protocol.

We report on the light pulse storage in Pr3+:Y2SiO5 crystal based on the revival of silenced echo protocol, which has the advantage of being immune from the spontaneous emission noise. We optimized the echo retrieval efficiency of the light pulse by employing complex hyperbolic secant rephasing pulses and by finely tuning the optical depth in the inhomogeneous broadening of the crystal. An echo retrieval efficiency of 24.4% was demonstrated, and an optical coherence time of 34.6 µs was extracted from the measured decay dynamics of the echo retrieval efficiency at a cryogenic temperature of 3.4 K. These results could be useful for potential applications in quantum memory and related applications.

Epiberberine inhibits bone metastatic breast cancer-induced osteolysis.

ETHNOPHARMACOLOGICAL RELEVANCE: The anti-tumor related diseases of Coptidis Rhizoma (Huanglian) were correlated with its traditional use of removing damp-heat, clearing internal fire, and counteracting toxicity. In the recent years, Coptidis Rhizoma and its components have drawn extensive attention toward their anti-tumor related diseases. Besides, Coptidis Rhizoma is traditionally used as an anti-inflammatory herb. Epiberberine (EPI) is a significant alkaloid isolated from Coptidis Rhizoma, and exhibits multiple pharmacological activities including anti-inflammatory. However, the effect of epiberberine on breast cancer and the inflammatory factors of metastatic breast cancer-induced osteolysis has not been demonstrated clearly. AIM OF THE STUDY: Bone metastatic breast cancer can lead to osteolysis via inflammatory factors-induced osteoclast differentiation and function. In this study, we try to analyze the effect of epiberberine on breast cancer and the inflammatory factors of metastatic breast cancer-induced osteolysis. METHODS: To evaluate whether epiberberine could suppress bone metastatic breast cancer-induced osteolytic damage, healthy female Balb/c mice were intratibially injected with murine triple-negative breast cancer 4T1 cells. Then, we examined the inhibitory effect and underlying mechanism of epiberberine on breast cancer-induced osteoclastogenesis in vitro. Xenograft assay was used to study the effect of epiberberine on breast cancer cells in vivo. Moreover, we also studied the inhibitory effects and underlying mechanisms of epiberberine on RANKL-induced osteoclast differentiation and function in vitro. RESULTS: The results show that epiberberine displayed potential therapeutic effects on breast cancer-induced osteolytic damage. Besides, our results show that epiberberine inhibited breast cancer cells-induced osteoclast differentiation and function by inhibiting secreted inflammatory cytokines such as IL-8. Importantly, we found that epiberberine directly inhibited RANKL-induced differentiation and function of osteoclast without cytotoxicity. Mechanistically, epiberberine inhibited RANKL-induced osteoclastogensis via Akt/c-Fos signaling pathway. Furthermore, epiberberine combined with docetaxel effectively protected against bone loss induced by metastatic breast cancer cells. CONCLUSIONS: Our findings suggested that epiberberine may be a promising natural compound for treating bone metastatic breast cancer-induced osteolytic damage by inhibiting IL-8 and is worthy of further exploration in preclinical and clinical trials.

The role of Tetraspanins in digestive system tumor development: update and emerging evidence.

Digestive system malignancies, including cancers of the esophagus, pancreas, stomach, liver, and colorectum, are the leading causes of cancer-related deaths worldwide due to their high morbidity and poor prognosis. The lack of effective early diagnosis methods is a significant factor contributing to the poor prognosis for these malignancies. Tetraspanins (Tspans) are a superfamily of 4-transmembrane proteins (TM4SF), classified as low-molecular-weight glycoproteins, with 33 Tspan family members identified in humans to date. They interact with other membrane proteins or TM4SF members to form a functional platform on the cytoplasmic membrane called Tspan-enriched microdomain and serve multiple functions including cell adhesion, migration, propagation and signal transduction. In this review, we summarize the various roles of Tspans in the progression of digestive system tumors and the underlying molecular mechanisms in recent years. Generally, the expression of CD9, CD151, Tspan1, Tspan5, Tspan8, Tspan12, Tspan15, and Tspan31 are upregulated, facilitating the migration and invasion of digestive system cancer cells. Conversely, Tspan7, CD82, CD63, Tspan7, and Tspan9 are downregulated, suppressing digestive system tumor cell metastasis. Furthermore, the connection between Tspans and the metastasis of malignant bone tumors is reviewed. We also summarize the potential role of Tspans as novel immunotherapy targets and as an approach to overcome drug resistance. Finally, we discuss the potential clinical value and therapeutic targets of Tspans in the treatments of digestive system malignancies and provide some guidance for future research.

Identification of TACSTD2 as novel therapeutic targets for cisplatin-induced acute kidney injury by multi-omics data integration.

Cisplatin-induced acute kidney injury (CP-AKI) is a common complication in cancer patients. Although ferroptosis is believed to contribute to the progression of CP-AKI, its mechanisms remain incompletely understood. In this study, after initially processed individual omics datasets, we integrated multi-omics data to construct a ferroptosis network in the kidney, resulting in the identification of the key driver TACSTD2. In vitro and in vivo results showed that TACSTD2 was notably upregulated in cisplatin-treated kidneys and BUMPT cells. Overexpression of TACSTD2 accelerated ferroptosis, while its gene disruption decelerated ferroptosis, likely mediated by its potential downstream targets HMGB1, IRF6, and LCN2. Drug prediction and molecular docking were further used to propose that drugs targeting TACSTD2 may have therapeutic potential in CP-AKI, such as parthenolide, progesterone, premarin, estradiol and rosiglitazone. Our findings suggest a significant association between ferroptosis and the development of CP-AKI, with TACSTD2 playing a crucial role in modulating ferroptosis, which provides novel perspectives on the pathogenesis and treatment of CP-AKI.

Involucrasin B Inhibits the Proliferation of Caco-2 Cells by Regulating the TGFß/SMAD2-3-4 Pathway.

(1) Background: Colorectal cancer (CRC) is the third most common malignant tumor worldwide and the second most common cause of cancer death. However, effective anti-CRC drugs are still lacking in clinical settings. This article investigated the anti-proliferative effect of involucrasin B on CRC Caco-2 cells. (2) Methods: This study employed a sulforhodamine B (SRB) method, colony formation experiments, flow cytometry, FastFUCCI assay, dual luciferase assay, and Western blot analysis for the investigation. (3) Results: The SRB method and colony formation experiments showed that involucrasin B exhibited an inhibitory effect on the Caco-2 cells cultured in vitro. Subsequently, the flow cytometry, FastFUCCI assay, and Western blotting results showed that involucrasin B induced cell cycle arrest in the G1 phase dose-dependently. Involucrasin B significantly enhanced the TGFß RII protein level and SMAD3 phosphorylation, thus inhibiting the expression of CDK4 and cyclin D1 and causing G1 cell cycle arrest. (4) Conclusion: This study shows that involucrasin B exerts its anti-proliferative effect by regulating the TGFß/SMAD2-3-4 pathway to cause G1 cycle arrest in Caco-2 cells.

A double-crack structure for bionic wearable strain sensors with ultra-high sensitivity and a wide sensing range.

Flexible strain sensors are crucial in fully monitoring human motion, and they should have a wide sensing range and ultra-high sensitivity. Herein, inspired by lyriform organs, a flexible strain sensor based on the double-crack structure is designed. An MXene layer and an Au layer with cracks are constructed on both sides of the insulated polydimethylsiloxane (PDMS) film, forming an equivalent parallel circuit that guarantees the integrity of the conductive path under a large strain. The rapid disconnection of the crack junctions causes a significant change in the resistance value. Due to the effect of cracks on the conductive path, the sensitivity of the sensor is largely improved. Benefiting from the double-crack structure, the as-obtained sensor shows ultra-high sensitivity (maximum gauge factor of up to 14 373.6), a wide working range (up to 21%), a fast response time (183 ms) and excellent dynamical stability (almost no performance loss after 1000 stretching cycles and different frequency cycles). In practical applications, the sensor is applied to different parts of the human body to sense the deformation of the skin, demonstrating its great potential application value in human physiological detection and the human-machine interaction. This study can provide new ideas for preparing high-performance flexible strain sensors.

LumVertCancNet: A novel 3D lumbar vertebral body cancellous bone location and segmentation method based on hybrid Swin-transformer.

Lumbar vertebral body cancellous bone location and segmentation is crucial in an automated lumbar spine processing pipeline. Accurate and reliable analysis of lumbar spine image is expected to advantage practical medical diagnosis and population-based analysis of bone strength. However, the design of automated algorithms for lumbar spine processing is demanding due to significant anatomical variations and scarcity of publicly available data. In recent years, convolutional neural network (CNN) and vision transformers (Vits) have been the de facto standard in medical image segmentation. Although adept at capturing global features, the inherent bias of locality and weight sharing of CNN constrains its capacity to model long-range dependency. In contrast, Vits excel at long-range dependency modeling, but they may not generalize well with limited datasets due to the lack of inductive biases inherent to CNN. In this paper, we propose a deep learning-based two-stage coarse-to-fine solution to address the problem of automatic location and segmentation of lumbar vertebral body cancellous bone. Specifically, in the first stage, a Swin-transformer based model is applied to predict the heatmap of lumbar vertebral body centroids. Considering the characteristic anatomical structure of lumbar spine, we propose a novel loss function called LumAnatomy loss, which enforces the order and bend of the predicted vertebral body centroids. To inherit the excellence of CNN and Vits while preventing their respective limitations, in the second stage, we propose an encoder-decoder network to segment the identified lumbar vertebral body cancellous bone, which consists of two parallel encoders, i.e., a Swin-transformer encoder and a CNN encoder. To enhance the combination of CNNs and Vits, we propose a novel multi-scale attention feature fusion module (MSA-FFM), which address issues that arise when fusing features given at different encoders. To tackle the issue of lack of data, we raise the first large-scale lumbar vertebral body cancellous bone segmentation dataset called LumVBCanSeg containing a total of 185 CT scans annotated at voxel level by 3 physicians. Extensive experimental results on the LumVBCanSeg dataset demonstrate the proposed algorithm outperform other state-of-the-art medical image segmentation methods. The data is publicly available at: https://zenodo.org/record/8181250. The implementation of the proposed method is available at: https://github.com/sia405yd/LumVertCancNet.

Seco-nortriterpenoids from Cirsium setosum and their anti-inflammatory activity.

Five unusual seco-nortriterpenoids, 3ß-hydroxy-20,21-seco-30-nortaraxastan-20,21-dioic acid (1), 3ß-hydroxy-20,21-seco-30-nortaraxastan-20-oic-21-oate (2), 3ß-hydroxy-20-oxo-21,22-seco-30-nortaraxastan-22-oic acid (3), 3ß-hydroxy-19-oxo-20,21-seco-29,30-nortaraxastan-21-oic acid (4) and 3ß-hydroxy-19-oxo-20,21-seco-19-norlupan-21-oic acid (5) were isolated and elucidated from the anti-inflammatory activity fraction of the ethanol extract of Cirsium setosum. The structures of these compounds were established through spectroscopic methods. Preliminary biological assays showed that compounds 1-5 had significant inhibitory effect on NO production on lipopolysaccharide-stimulated RAW 264.7 cells, and compound 1 showed the strongest anti-inflammatory activity. This type of ring-opening compound is the first seco-triterpenoid structure discovered from the genus of Cirsium.

A new modified MR dual precision positioning of thin-slice oblique sagittal fat suppression proton density weighted imaging: its diagnostic accuracy in anterior cruciate ligament injury.

To evaluate the diagnostic accuracy of a new modified MR dual precision positioning of thin-slice oblique sagittal fat suppression proton density-weighted imaging (DPP-TSO-Sag-FS-PDWI) sequence in detecting ACL injuries and its grades compared to standard sequences using arthroscopy as the standard reference. 42 patients enrolled in this retrospective study received the 1.5-T MRI with standard sequences and the new modified DPP-TSO-Sag-FS-PDWI sequence, and their arthroscopy results was recorded. The Mc Nemer-Bowker and weighted Kappa was performed to compare the consistency of MRI diagnosis with arthroscopic results. Finally, the diagnostic accuracy was calculated based on the true positive, true negative, false negative and false positive values. The diagnostic consistency of the DPP-TSO-Sag-FS-PDWI were higher than standard sequences for both reader 1 (K = 0.876 vs. 0.620) and reader 2 (K = 0.833 vs. 0.683) with good diagnostic repeatability (K = 0.794 vs. 0.598). Furthermore, the DPP-TSO-Sag-FS-PDWI can classify and diagnose three grades of ACL injury [the sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value were more than 84%], especially for grade II injury as the PPV was superior for reader 1 (92.3% vs. 53.9%) and reader 2 (84.6% vs. 69.2%). The new modified DPP-TSO-Sag-FS-PDWI sequence can display the ACL injury on one or continuous levels by maximizing the acquisition of complete ligament shape and true anatomical images, and excluding the influence of anatomical differences between individuals. It can improve the diagnostic accuracy with good repeatability and classify three grades of the ACL injury.

Ultrahigh Degree of Cationic Disorder, Configurational Entropy in New Type of High-Entropy Pseudobrookite Phase.

High-entropy ceramics exhibit various excellent properties owing to their high configurational entropy, which is caused by multi-principal elements sharing one lattice site. The configurational entropy will further increase significantly if multi-principal elements randomly share two different lattice sites. For this purpose, pseudobrookite phase containing two cationic lattice sites (A and B sites) is selected, and corresponding high-entropy pseudobrookite (M2+ 0.4 M3+ 1.2 )Ti1.4 O5 is synthesized. Herein, the distribution of the 2-valent and 3-valent cations in the A and B sites are analysed in depth. The distance between the A and B sites in the crystal structure models which are constructed by the Rietveld analysis is calculated and defined as distance d. Meanwhile, the atomic column positions in the STEM images are quantified by a model-based mathematical algorithm, and the corresponding distance d are calculated. By comparing the distance d, it is determine that the 2-valent and 3-valent cations are jointly and disorderly distributed in the A and B sites in high-entropy (M2+ 0.4 M3+ 1.2 )Ti1.4 O5 . The density functional theory (DFT) simulations also demonstrate that this type of crystal structure is more thermodynamically stable. The higher degree of cationic disorder leads to a higher configurational entropy in high-entropy (M2+ 0.4 M3+ 1.2 )Ti1.4 O5 , and endows high-entropy (M2+ 0.4 M3+ 1.2 )Ti1.4 O5 with very low thermal conductivity (1.187-1.249 W m-1  K-1 ).

The Effect of Different Diluents and Curing Agents on the Performance of Epoxy Resin-Based Intumescent Flame-Retardant Coatings.

The epoxy resin-based (ESB) intumescent flame-retardant coatings were modified with 1,4-butanediol diglycidyl ether (14BDDE) and butyl glycidyl ether (BGE) as diluents and T403 and 4,4'-diaminodiphenylmethane (DDM) as curing agents, respectively. The effects of different diluents and curing agents on the flame-retardant and mechanical properties, as well as the composition evolution of the coatings, were investigated by using large-plate combustion, the limiting oxygen index (LOI), vertical combustion, a cone calorimeter, X-ray diffraction, FTIR analysis, a N2 adsorption and desorption test, a scanning electron microscope (SEM), a tensile strength test, and a viscosity test. The results showed that the addition of 14BBDE and T403 promoted the oxidation of B4C and the formation of boron-containing glass or ceramics, increased the residual mass of char, densified the surface char layer, and increased the specific surface area of porous residual char. When their dosage was 30%, ESB-1T-3 coating exhibited the most excellent flame-retardant properties. During the 2 h large-plate combustion test, the backside temperature was only 138.72 °C, without any melting pits. In addition, the peak heat release rate (PHRR), total heat release rate (THR), total smoke production (TSP), and peak smoke production (PSPR) were reduced by 13.15%, 13.9%, 5.48%, and 17.45%, respectively, compared to the blank ESB coating. The LOI value reached 33.4%, and the vertical combustion grade was V-0. In addition, the tensile strength of the ESB-1T-3 sample was increased by 10.94% compared to ESB. In contrast, the addition of BGE and DDM promoted the combustion of the coating, affected the ceramic process of the coating, seriously affected the formation of borosilicate glass, and exhibited poor flame retardancy. The backside temperature reached 190.93 °C after 2 h combustion. A unified rule is that as the amount of diluent and curing agent increases, the flame retardancy improves while the mechanical properties decrease. This work provides data support for the preparation and process optimization of resin-based coatings.