Titanium alloys are difficult to machine using conventional methods, therefore, nonconventional processes are often chosen in many applications. Electrical discharge machining (EDM) is one of those nonconventional processes that is used frequently for shaping titanium alloys with their respective pros and cons. However, a good understanding of this process is very difficult to achieve as research results are not properly connected and presented. Therefore, this study investigates different types of EDM processes such as, wire EDM, die-sink EDM, EDM drill and hybrid EDM used to machine titanium alloys. Machining mechanism, tool electrode, dielectric, materials removal rate (MRR), and surface integrity of all these processes are critically analysed and correlated based on the evidence accessible in literature. Machining process suffer from lower material removal rate and high tool wear while applied on titanium alloys. Formation of recast layer, heat affected zone and tool wear is common in all types of EDM processes. Additional challenge in wire EDM of titanium alloys is wire breakage under severe machining conditions. The formation of TiC and TiO2 are noticed in recast layer depending on the type of dielectrics. Removal of debris from small holes during EDM drilling is a challenge. All these restricts the applications EDMed titanium alloys in high-tech applications such as, aerospace and biomedical areas. Most of these challenges come up due to extraordinary properties such as, low thermal conductivity, high melting point and high hardness, of titanium alloys. Though hybrid EDM has been introduced and there is some work on simulation of EDM process, further developments in EDM of this alloy is required for widening the application of this methods.
Lipidic nanoparticles have undergone extensive research toward the exploration of their diverse therapeutic applications. Although several liposomal formulations are in the clinic (e.g., DOXIL) for cancer therapy, there are many challenges associated with traditional liposomes. To address these issues, modifications in liposomal structure and further functionalization are desirable, leading to the emergence of solid lipid nanoparticles and the more recent liquid lipid nanoparticles. In this context, "cubosomes", third-generation lipidic nanocarriers, have attracted significant attention due to their numerous advantages, including their porous structure, structural adaptability, high encapsulation efficiency resulting from their extensive internal surface area, enhanced stability, and biocompatibility. Cubosomes offer the potential for both enhanced cellular uptake and controlled release of encapsulated payloads. Beyond cancer therapy, cubosomes have demonstrated effectiveness in wound healing, antibacterial treatments, and various dermatological applications. In this review, the authors provide an overview of the evolution of lipidic nanocarriers, spanning from conventional liposomes to solid lipid nanoparticles, with a special emphasis on the development and application of cubosomes. Additionally, it delves into recent applications and preclinical trials associated with cubosome formulations, which could be of significant interest to readers from backgrounds in nanomedicine and clinicians.
In the present research work, an effort has been made to explore the potential of using the adhesive tapes while drilling CFRPs. The input parameters, such as drill bit diameter, point angle, Scotch tape layers, spindle speed, and feed rate have been studied in response to thrust force, torque, circularity, diameter error, surface roughness, and delamination occurring during drilling. It has been found that the increase in point angle increased the delamination, while increase in Scotch tape layers reduced delamination. The surface roughness decreased with the increase in drill diameter and point angle, while it increased with the speed, feed rate, and tape layer. The best low roughness was obtained at 6 mm diameter, 130° point angle, 0.11 mm/rev feed rate, and 2250 rpm speed at three layers of Scotch tape. The circularity error initially increased with drill bit diameter and point angle, but then decreased sharply with further increase in the drill bit diameter. Further, the circularity error has non-linear behavior with the speed, feed rate, and tape layer. Low circularity error has been obtained at 4 mm diameter, 118° point angle, 0.1 mm/rev feed rate, and 2500 RPM speed at three layers of Scotch tape. The low diameter error has been obtained at 6 mm diameter, 130° point angle, 0.12 mm/rev feed rate, and 2500 rpm speed at three layer Scotch tape. From the optical micro-graphs of drilled holes, it has been found that the point angle is one of the most effective process parameters that significantly affects the delamination mechanism, followed by Scotch tape layers as compared to other parameters such as drill bit diameter, spindle speed, and feed rate.
In this investigation, biodegradable composites were fabricated with polycaprolactone (PCL) matrix reinforced with pine cone powder (15%, 30%, and 45% by weight) and compatibilized with graphite powder (0%, 5%, 10%, and 15% by weight) in polycaprolactone matrix by compression molding technique. The samples were prepared as per ASTM standard and tested for dimensional stability, biodegradability, and fracture energy with scanning electron micrographs. Water-absorption and thickness-swelling were performed to examine the dimensional stability and tests were performed at 23 °C and 50% humidity. Results revealed that the composites with 15 wt % of pine cone powder (PCP) have shown higher dimensional stability as compared to other composites. Bio-composites containing 15-45 wt % of PCP with low graphite content have shown higher disintegration rate than neat PCL. Fracture energy for crack initiation in bio-composites was increased by 68% with 30% PCP. Scanning electron microscopy (SEM) of the composites have shown evenly-distributed PCP particles throughout PCL-matrix at significantly high-degrees or quantities of reinforcing.
Nanomedicines, while having been approved for cancer therapy, present many challenges such as low stability, rapid clearance, and nonspecificity leading to off-target toxicity. Cubosomes are porous lyotropic liquid crystalline nanoparticles that have shown great premise as drug delivery vehicles; however, their behavior in vivo is largely underexplored, hindering clinical translation. Here, we have engineered cubosomes based on the space group Im3m that are loaded with copper acetylacetonate as a model drug, and their surfaces are functionalized for the first time with Affimer proteins via copper-free click chemistry to actively target overexpressed carcinoembryonic antigens on LS174T colorectal cancer cells. Unlike nontargeted cubosomes, Affimer tagged cubosomes showed preferential accumulation in cancer cells compared to normal cells not only in vitro (2D monolayer cell culture and 3D spheroid models) but also in vivo in colorectal cancer mouse xenografts, while exhibiting low nonspecific absorption and toxicity in other vital organs. Cancerous spheroids had maximum cell death compared to noncancerous cells upon targeted delivery. Xenografts subjected to targeted drug-loaded cubosomes showed a 5-7-fold higher drug accumulation in the tumor tissue compared to the liver, kidneys, and other vital organs, a significant decrease in tumor growth, and an increased survival rate compared to the nontargeted group. This work encompasses the first thorough preclinical investigation of Affimer targeted cubosomes as a cancer therapeutic.
Cancer is a group of diseases marked by unchecked cell proliferation and the ability for the disease to metastasize to different body areas. Enhancements in treatment and early detection are crucial for improved outcomes. LncRNAs are RNA molecules that encode proteins and have a length of more than 200 nucleotides. LncRNAs are crucial for chromatin architecture, gene regulation, and other cellular activities that impact both normal growth & pathological processes, even though they are unable to code for proteins. LncRNAs have emerged as significant regulators in the study of cancer biology, with a focus on their intricate function in the Notch signaling pathway. The imbalance of this pathway is often linked to a variety of malignancies. Notch signaling is essential for cellular functions like proliferation, differentiation, and death. The cellular response is shaped by these lncRNAs through their modulation of essential Notch pathway constituents such as receptors, ligands, and downstream effectors around it. Furthermore, a variety of cancer types exhibit irregular expression of Notch-related lncRNAs, underscoring their potential use as therapeutic targets and diagnostic markers. Gaining an understanding of the molecular processes behind the interaction between the Notch pathway and lncRNAs will help you better understand the intricate regulatory networks that control the development of cancer. This can open up new possibilities for individualized treatment plans and focused therapeutic interventions. The intricate relationships between lncRNAs & the Notch pathway in cancer are examined in this review.
Theranostic nanoparticles hold promise for simultaneous imaging and therapy in colorectal cancer. Carcinoembryonic antigen can be used as a target for these nanoparticles because it is overexpressed in most colorectal cancers. Affimer reagents are synthetic proteins capable of binding specific targets, with additional advantages over antibodies for targeting. We fabricated silica nanoparticles using a water-in-oil microemulsion technique, loaded them with the photosensitiser Foslip, and functionalised the surface with anti-CEA Affimers to facilitate fluorescence imaging and photodynamic therapy of colorectal cancer. CEA-specific fluorescence imaging and phototoxicity were quantified in colorectal cancer cell lines and a LS174T murine xenograft colorectal cancer model. Anti-CEA targeted nanoparticles exhibited CEA-specific fluorescence in the LoVo, LS174T and HCT116 cell lines when compared to control particles (p < 0.0001). No toxicity was observed in LS174T cancer mouse xenografts or other organs. Following photo-irradiation, the anti-CEA targeted particles caused significant cell death in LoVo (60%), LS174T (90%) and HCT116 (70%) compared to controls (p < 0.0001). Photodynamic therapy (PDT) at 24 h in vivo showed a 4-fold reduction in tumour volume compared to control mouse xenografts (p < 0.0001). This study demonstrates the efficacy of targeted fluorescence imaging and PDT using Foslip nanoparticles conjugated to anti-CEA Affimer nanoparticles in in vitro and in vivo colorectal cancer models.