UCP2 is an uncoupling protein homolog to UCP1. Unlike UCP1, which participates in non-shivering thermogenesis by uncoupling oxidative phosphorylation (OXPHOS), UCP2 does not perform a canonical H⁺ leak, consuming the protonmotive force (Δp) through the inner mitochondrial membrane. The UCP2 biological role is elusive. It can counteract oxidative stress, acting with a “mild uncoupling” process to reduce ROS production, and, in fact, UCP2 activities are related to inflammatory processes, triggering pathological conditions. However, the Δp dissipation by UCP2 activity reduces the mitochondrial ATP production and rewires the bioenergetic metabolism of the cells. In all likelihood, UCP2 works as a carrier of metabolites with four carbon atoms (C4), reversing the anaerobic glycolysis-dependent catabolism to OXPHOS. Indeed, UCP2 can perform catalysis in dual mode: mild uncoupling of OXPHOS and metabolite C4 exchange of mitochondria. In vivo, the UCP2 features in the biology of mitochondria promote healthy ageing, increased lifespan, and can assure cerebro- and cardiovascular protection. However, the pathological conditions responsible for insulin secretion suppression are dependent on UCP2 activity. On balance, the uncertain biochemical mechanisms dependent on UCP2 do not allow us to depict the protective role in mitochondrial bioenergetics. Full article

Using semiochemicals collected from spotted lanternflies Lycorma delicatula (Hemiptera: Fulgoridae) (SLF) and deployed in the field with circle traps, we demonstrated that SLF responded to SLF pheromones: in particular, this was the case for males while seeking mates and for females while ovipositing. The attractants consisted of SLF body extract emitted from diffuser lures and SLF honeydew on burlap ribbons, collected from heavily infested locations. Traps with attractants were deployed in field sites with very light SLF infestations to avoid competing signals of pre-existing aggregations. The number of SLF equivalents emitted by each diffuser per trapping period was used in a dose–response analysis. Three trees per block received either (1) a control hexane lure and a clean ribbon, (2) a lure containing SLF extract and a clean ribbon, or (3) a lure containing SLF extract and a honeydew-laden ribbon. Ten blocks were sampled three times per week for twelve weeks. We found a significant positive dose–response by males to SLF body extract only in the presence of SLF honeydew, indicating a synergistic effect between honeydew volatiles and body volatiles. This dose–response occurred for five weeks after mating started, after which males no longer responded. Subsequently, females had a significant positive dose–response to SLF extract only in the presence of honeydew when oviposition was their primary activity, continuing for two weeks, suggesting that females may use pheromones to aggregate for oviposition. The extract in the absence of honeydew did not result in a positive dose–response, nor did the hexane control. These findings suggest that SLF respond synergistically to the combination of pheromones present in both SLF honeydew and SLF bodies. Thus, combining key components from both sources may aid the development of semiochemical lures for SLF. Full article

Whole-body vibration (WBV) is a widely used training method to increase muscle strength and power. However, its working mechanisms are still poorly understood, and studies investigating the effects of WBV on muscle stiffness are scant. Therefore, the aim of this study is to investigate the acute effects of WBV on stiffness and countermovement jump (CMJ). Twenty-four recreationally active males, on separate days and in random order, performed a static squat under two different conditions: with WBV (WBV) or without vibration (CC). Muscle stiffness was assessed through the Wartenberg pendulum test, and CMJ was recorded. RM-ANOVA was employed to test differences between conditions in the above-mentioned variables. In the CC condition, stiffness was significantly lower after the exposure to the static squat (p = 0.006), whereas no difference was observed after the exposure to WBV. WBV and CC did not affect CMJ. No significant correlation was observed between changes in CMJ and changes in stiffness. Our results show that WBV may mitigate the reduction in muscle stiffness observed after static squats. However, current results do not support the notion that WBV exposure may account for an increase in CMJ performance. Full article

Bridges are one of the most critical and costly structures on road networks. Thus, their integrity and operation must be preserved to prevent safety concerns and connectivity losses after seismic events. Recent large-magnitude earthquakes have revealed a series of vulnerabilities in multi-span highway bridges. In particular, skewed bridges have been severely damaged due to their susceptibility to developing excessive in-plane deck rotations and span unseating. Although seismic design codes have been updated to prescribe larger seating lengths and have incorporated unseating prevention devices, such as shear keys and cable restrainers, research on the seismic performance of skewed bridges with passive energy-dissipation devices is still limited. Therefore, this study focuses on assessing the effectiveness of implementing hysteretic dampers on skewed bridges. With that aim, dampers with and without recentering capabilities are designed and incorporated in representative Chilean skewed bridges to assess their contribution to seismic performance. Three-dimensional nonlinear finite element models, multiple-stripe analysis, and fragility curves are utilized to achieve this objective. The results show that incorporating bidirectional dampers can effectively improve the seismic performance of skewed bridges at different hazard levels by limiting in-plane deck rotations independently of their skew angle. Additionally, the influence of external shear keys and damper hysteretic behavior is analyzed, showing that these parameters have a low influence on bridge performance when bidirectional dampers are incorporated. Full article

Oxidative stress can damage tissues and cells, and their resilience or susceptibility depends on the robustness of their antioxidant mechanisms. The latter include small molecules, proteins, and enzymes, which are linked together in metabolic pathways. Red blood cells are particularly susceptible to oxidative stress due to their large number of hemoglobin molecules, which can undergo auto-oxidation. This yields reactive oxygen species that participate in Fenton chemistry, ultimately damaging their membranes and cytosolic constituents. Fortunately, red blood cells contain robust antioxidant systems to enable them to circulate and perform their physiological functions, particularly delivering oxygen and removing carbon dioxide. Nonetheless, if red blood cells have insufficient antioxidant reserves (e.g., due to genetics, diet, disease, or toxin exposure), this can induce hemolysis in vivo or enhance susceptibility to a “storage lesion” in vitro, when blood donations are refrigerator-stored for transfusion purposes. Ergothioneine, a small molecule not synthesized by mammals, is obtained only through the diet. It is absorbed from the gut and enters cells using a highly specific transporter (i.e., SLC22A4). Certain cells and tissues, particularly red blood cells, contain high ergothioneine levels. Although no deficiency-related disease has been identified, evidence suggests ergothioneine may be a beneficial “nutraceutical.” Given the requirements of red blood cells to resist oxidative stress and their high ergothioneine content, this review discusses ergothioneine’s potential importance in protecting these cells and identifies knowledge gaps regarding its relevance in enhancing red blood cell circulatory, storage, and transfusion quality. Full article

There is a growing concern about limited water supply and water scarcity in many river basins across the world. The agricultural sector is the largest user of freshwater on the planet, with a growing amount of water extracted for livestock systems. Here, we use data from the GLEAM model to advance previous studies that estimated livestock water footprints by quantifying water use for feed production, animal drinking water, and animal service water. We additionally account for the role of trade in accounting for feed water allocations to different animals in different countries and make use of a hydrologic model to estimate feed irrigation water requirements for individual crops at a high spatial resolution. Lastly, we estimate the contribution of livestock water abstractions to water stress at a small river basin scale for the entire globe. We find that feed production water accounts for the majority (>90%) of global livestock water withdrawals, though there is regional variation. Similarly, we find large regional variation in the water consumption per head by livestock species. Despite consuming >200 km³ of water per year, we find that reducing water use in the livestock system alone will rarely reduce water stress in high-stress basins. This study highlights the need for quantifying locally relevant water use and water stress metrics for individual livestock systems. Full article

Background/Objectives: We defined the value of a machine learning algorithm to distinguish between the EEG response to no light or any light stimulations, and between light stimulations with different brightnesses in awake volunteers with closed eyelids. This new method utilizing EEG analysis is visionary in the understanding of visual signal processing and will facilitate the deepening of our knowledge concerning anesthetic research. Methods: X-gradient boosting models were used to classify the cortical response to visual stimulation (no light vs. light stimulations and two lights with different brightnesses). For each of the two classifications, three scenarios were tested: training and prediction in all participants (all), training and prediction in one participant (individual), and training across all but one participant with prediction performed in the participant left out (one out). Results: Ninety-four Caucasian adults were included. The machine learning algorithm had a very high predictive value and accuracy in differentiating between no light and any light stimulations (AUCROC_all: 0.96; accuracy_all: 0.94; AUCROC_individual: 0.96 ± 0.05, accuracy_individual: 0.94 ± 0.05; AUCROC_oneout: 0.98 ± 0.04; accuracy_oneout: 0.96 ± 0.04). The machine learning algorithm was highly predictive and accurate in distinguishing between light stimulations with different brightnesses (AUCROC_all: 0.97; accuracy_all: 0.91; AUCROC_individual: 0.98 ± 0.04, accuracy_individual: 0.96 ± 0.04; AUCROC_oneout: 0.96 ± 0.05; accuracy_oneout: 0.93 ± 0.06). The predictive value and accuracy of both classification tasks was comparable between males and females. Conclusions: Machine learning algorithms could almost continuously and reliably differentiate between the cortical EEG responses to no light or light stimulations using visual evoked potentials in awake female and male volunteers with eyes closed. Our findings may open new possibilities for the use of visual evoked potentials in the clinical and intraoperative setting. Full article

The quality of cotton fiber plays a pivotal role for both producers and processors, influencing the market value and end-product quality. Certain cotton fiber properties, such as length, strength, micronaire, and uniformity index, are crucial determinants of cotton quality. Despite its prominence as a cotton-producing region, the Aegean region in Türkiye lacks comprehensive studies examining the quality of its cotton fiber across different subregions and seasonal variations. This study aimed to address this gap by investigating the variations in cotton fiber quality across different years and subregions within the Aegean. This study involved the evaluation of a total of 368,686 individual fiber quality analyses conducted over seven years across three subregions within the Aegean in Türkiye. The fiber samples collected from Bergama, Söke, and Menemen underwent high-volume instrument (HVI) analysis to evaluate the variations in cotton fiber quality across years and subregions, considering the phenological stages of cotton and climate conditions. The findings highlighted significant variations in the fiber quality traits among subregions, with environmental factors such as temperature and humidity playing crucial roles. Higher average daily temperatures during the flowering stage to boll formation contributed to higher strength values, while limitations on fiber length were observed due to prevalent high temperatures. Additionally, variations in micronaire values were linked to temperature and humidity conditions during boll development stages. This study underscores the importance of comprehensively considering climatic factors to understand their impacts on cotton fiber quality and suggests further research into the cotton plant’s phenology and specific climate conditions for a more thorough understanding of environmental effects on fiber quality. Full article

The nitrogen-stable isotopes of plants can be used to verify the source of fertilizers, but the fertilizer uptake patterns in tea (Camellia sinensis) plants are unclear. In this study, potted tea plants were treated with three types of organic fertilizers (OFs), urea, and a control. The tea leaves were sampled over seven months from the top, middle, and base of the plants and analyzed for the δ¹⁵N and nitrogen content, along with the corresponding soil samples. The top tea leaves treated with the rapeseed cake OF had the highest δ¹⁵N values (up to 6.6‰), followed by the chicken manure, the cow manure, the control, and the urea fertilizer (6.5‰, 4.1‰, 2.2‰, and 0.6‰, respectively). The soil treated with cow manure had the highest δ¹⁵N values (6.0‰), followed by the chicken manure, rapeseed cake, control, and urea fertilizer (4.8‰, 4.0‰, 2.5‰, and 1.9‰, respectively). The tea leaves fertilized with rapeseed cake showed only slight δ¹⁵N value changes in autumn but increased significantly in early spring and then decreased in late spring, consistent with the delivery of a slow-release fertilizer. Meanwhile, the δ¹⁵N values of the top, middle, and basal leaves from the tea plants treated with the rapeseed cake treatment were consistently higher in early spring and lower in autumn and late spring, respectively. The urea and control samples had lower tea leaf δ¹⁵N values than the rapeseed cake-treated tea and showed a generalized decrease in the tea leaf δ¹⁵N values over time. The results clarify the temporal nitrogen patterns and isotope compositions of tea leaves treated with different fertilizer types and ensure that the δ¹⁵N tea leaf values can be used to authenticate the organic fertilizer methods across different harvest periods and leaf locations. The present results based on a pot experiment require further exploration in open agricultural soils in terms of the various potential fertilizer effects on the different variations of nitrogen isotope ratios in tea plants. Full article

Background: This computational analysis investigated sequence complementarities between the TRIM33 gene and human noncoding (nc)RNAs and characterized their interactions in the context of paraneoplastic dermatomyositis. Methods: TRIM33 FASTA sequence (NCBI Reference Sequence: NC_000001.11) was used for BLASTN analysis against Human GRCh38 in the Ensembl.org database. Retrieved ncRNAs showing hits to TRIM33 were searched in the GeneCards.org database and further analyzed through RNAInter, QmRLFS-finder, Spliceator, and NcPath enrichment analysis. Results: A total of 100 hits were found, involving the lncRNAs NNT-AS1, MKLN1-AS, LINC01206, and PAXBP1-AS1, whose dysregulation has been reported in either cancer or dermatomyositis. Additionally, the lncRNAs NNT-AS1 and PAXBP1-AS1 may interact with microRNA-142-3p, reducing its expression and increasing that of TRIM33. Sequence complementarity affected only TRIM33 intron 1, possibly resulting in alternatively spliced isoforms of TIF1γ with increased immunogenicity. The results also revealed nucleotide alignment between TRIM33 and the gene regulatory elements of 28 ncRNA genes involved in immune pathways. Conclusions: This pivotal study demonstrates sequence complementarity between TRIM33 and human ncRNAs dysregulated in cancer and dermatomyositis. This scenario may lead to the overproduction of more immunogenic TIF1γ variants in tumors and the stimulation of autoimmunity. Further experimental analyses using targeted methods such as Western blot or Chip-Seq are required to confirm these data. Full article

Bamboo is a typical natural fiber-reinforced composite with excellent mechanical properties, which are determined by its special micro-structure. As the reinforcing phase, the vascular bundles play a central role in the control of the mechanical properties of bamboo macro-structure. To find the exact gradient variation of the mechanical properties of these continuously distributed vascular bundles within the bamboo culm, 4-year-old Moso bamboo was chosen to investigate the variation of locate-distribution, cross-section area, and mechanical properties of single vascular bundles along the longitudinal and radial directions with respect to their location from the base, middle, and top sections of bamboo culm, respectively. It shows that the spatial distribution of vascular bundles along the column is distributed exponentially from the inside to the outside of the culm. The cross-section area of the vascular bundles decreased exponentially from the inside to the outside along the radial direction. All the vascular bundles were then carefully separated from bamboo strips and tested via the tensile tests. Test results show that the longitudinal tensile strengths of vascular bundles ranged from 180.44 to 774.10 MPa, and the longitudinal Young’s modulus ranged from 9.00 to 44.76 GPa. The tensile strength of vascular bundles at the outer side was three times higher than that of the inner side, while Young’s modulus at the outer side was three to four times higher than that of the inner side. For all three height positions, the strengths and Young’s modulus of vascular bundles are all exponentially increased from the inner side to the outer side along the radial direction. This work will provide a basis for the highly processed product’s application of bamboo resources and a reference for further study on the trans-scale analysis of the mechanical properties of bamboo. Full article

Research has extensively studied adult attachment theory, a fundamental psychological framework, particularly regarding its implications for adult attachment and sexual dynamics. The previous literature has established relationships between adult attachment and various sexual behaviours as well as communication patterns. Specifically, individuals with secure attachment styles typically engage in open communication and cautious sexual behaviours, whereas individuals with anxious or avoidant attachment styles exhibit less sexual communication and engage in riskier sexual activities. That said, limited research has explored the relationship between adult attachment style and perceived knowledge regarding partner sex history. This study aimed to fill this gap by investigating how adult attachment style relates to perceived knowledge about partner sexual experiences. A sample of 237 undergraduate students completed surveys assessing attachment style and their perceived awareness of their partner’s sexual past. Attachment style was evaluated using the Revised Adult Attachment Scale (RAAS) and perceived knowledge was measured using the Partner Sexual History Scale (PSHS). The results indicated a significant correlation between adult attachment style and perceived knowledge of a partner’s sexual history. Specifically, individuals with secure and avoidant attachment styles demonstrated greater perceived awareness of their partner’s sexual experiences compared to those with an anxious attachment style. This research contributes to our comprehension of the complex interplay among adult attachment, sexual knowledge, sexual communication, and relationship dynamics in young adult populations. Full article

The increasing rate of minimally invasive procedures and the growing prevalence of cardiovascular disease have led to a demand for higher-quality guidance systems for catheter tracking. Traditional methods for catheter tracking, such as detection based on single points and applying masking techniques, have been limited in their ability to provide accurate pose information. In this paper, we propose a novel deep learning-based method for catheter tracking and pose detection. Our method uses a Yolov5 bounding box neural network with postprocessing to perform landmark detection in four regions of the catheter: the tip, radio-opaque marker, bend, and entry point. This allows us to track the catheter’s position and orientation in real time, without the need for additional masking or segmentation techniques. We evaluated our method on a dataset of fluoroscopic images from two distinct datasets and achieved state-of-the-art results in terms of accuracy and robustness. Our model was able to detect all four landmark features (tip, marker, bend, and entry) used to generate a pose for a catheter with 0.285 ± 0.143 mm, 0.261 ± 0.138 mm, 0.424 ± 0.361 mm, and 0.235 ± 0.085 mm accuracy. We believe that our method has the potential to significantly improve the accuracy and efficiency of catheter tracking in medical procedures that utilize bi-plane fluoroscopy guidance. Full article

The characteristics of gap plasmon formed by nanoparticle-on-mirror (NPOM) structures composed of metal nanoparticles (MNPs) and metal thin films have aroused interest for use in various optoelectronic devices. The resonance enhancement characteristics in the gap region of an NPOM structure composed of gold nanoparticles and gold thin films are simulated theoretically by the finite element method (FEM). The resonant spectrum obtained by the internal coupling effect of the gap can be flexibly controlled by the polarization of incident light and the thickness of the dielectric layer between the MNPs and the metal thin films. We study the resonance spectra of polarization-dependent gold ellipsoidal nanoparticles (GENPs) and gold thin films in the gap region of an NPOM structure. The GENPs and gold thin films are separated by a dielectric layer with a refractive index of 1.36. We observe that the intensity of the resonance electric field in the gap region is inversely proportional to the polarization angle. Similarly, the intensity of the local electric field resonance peak in the gap region is inversely proportional to the thickness of the dielectric layer. When the thickness of the dielectric layer is 0.3 nm and the polarization angle is 0°, the best resonant electric field intensity of 2200 V/m is obtained in the gap region of the NPOM structure (the power of incident light is 1 mW). Finally, the resonant peak wavelength of the electric field in the gap region of the NPOM structure is also controlled by the polarization angle of the incident light and the thickness of the dielectric layer. Full article

The undercutting process is a technique employed to initiate the caving of the ore mass in block caving, achieved by creating a basal cut on the block scheduled to be submerged. The effective execution of the undercutting process involves numerous variables, such as the undercut height and the vertical section’s undercut geometry, whose influence has often been overlooked. This research presents a methodology for determining the undercut height in a post-undercutting scenario, including variables such as the undercut level design, the extraction level design, and the air gap. Integral to this methodology is a parameterization that estimates the undercut height, from which design abacuses can be created to aid the assessment of present and future operations for any block/panel caving operation that employs the post-undercutting variant. Additionally, two examples demonstrate the application of this methodology, revealing how alterations in the dimensions of the crown pillar and drawbells significantly influence the undercut height. The calculation methodology outlined in this document delivers an undercutting height, providing an evaluation methodology for ongoing operations. Consequently, any height exceeding this suggests a conservative approach, potentially offering an opportunity for design improvement and alignment with the described parameters. Full article

Talaromyces, a filamentous fungus widely distributed across terrestrial and marine environments, can produce a diverse array of natural products, including alkaloids, polyketones, and polyketide-terpenoids. Among these, chrodrimanins represented a typical class of natural products. In this study, we isolated three previously undescribed pentaketide-sesquiterpenes, 8,9-epi-chrodrimanins (1–3), along with eight known compounds (4–11). The structures of compounds 1–3 were elucidated using nuclear magnetic resonance (NMR) and mass spectrometry (MS), while their absolute configurations were determined through X-ray crystallography and electronic circular dichroism (ECD) computations. The biosynthetic pathways of compounds 1–3 initiate with 6-hydroxymellein and involve multiple stages of isoprenylation, cyclization, oxidation, and acetylation. We selected four strains of gastrointestinal cancer cells for activity evaluation. We found that compound 3 selectively inhibited MKN-45, whereas compounds 1 and 2 exhibited no significant inhibitory activity against the four cell lines. These findings suggested that 8,9-epi-chrodrimanins could serve as scaffold compounds for further structural modifications, potentially leading to the development of targeted therapies for gastric cancer. Full article

The pawpaw (Asimina triloba) is a tropical-tasting fruit from a tree indigenous to North America’s temperate climates. Pawpaw has a sweet, sour, and often bitter taste, which is a combination of banana and mango flavor. Fresh fruits are rarely available for retail purchase other than at farm sales or farmers’ markets. Frozen pulp is commercially available but supply is often limited due to increased wholesale demand. The purpose of this paper is to analyze seven years of entries from the Pawpaw Cookoff at the Ohio Pawpaw Festival using case study methodology to provide a basis from which to track trends, make recommendations, and discuss gastronomic opportunities of the pawpaw. Analysis of the data indicates that pawpaw is a versatile fruit that has been incorporated into a wide variety of beverages, savories, sauces, condiments, sweets, and desserts. Pawpaw pairs well with both alcoholic and non-alcoholic beverages, especially certain ales, sour beers, innovative cocktails with rum, coffee and tea drinks, and smoothies. Pawpaw is easily incorporated directly into salsas, dips, salad dressings, and frozen desserts that do not require cooking. In cooked savory dishes, sauces, and condiments, pawpaw should be added at the end of preparation. Pawpaw can be used in a wide range of baked and fried sweets and desserts. Full article

Patellar fractures represent approximately 1% of all fractures and the pattern is influenced by the quality of the bone and the energy of the trauma. Transverse fractures are associated with extensor mechanism failure and interruption of joint congruence. Patellar fractures are generally fixed using tension band principles, through K-wires and metal cerclage. The tension band was conceived to transform the considerable tensile force applied to the patella into a compressive one to obtain a stable fixation. The use of metal implants might be associated with a significant discomfort, mostly related to the irritating action of K-wires and cerclage on the surrounding soft tissues, often leading to the need for implant removal. Therefore, we introduced an original technique for fix patellar fractures by using only a non-adsorbable braided polyblend suture. Postoperative care included progressive range of motion recovery using an articulated knee brace and a specific protocol. The suture-only tension band technique seems to be a useful technique in terms of complications and reoperation rate while allowing secure and early mobilization. Full article

Graphene superlattices have simple and controllable electronic band structures, which can also be electrostatically tuned. They have been widely studied for band engineering and strong correlated physics, and have led to the discovery of a variety of exciting phenomena. To experimentally study the physics of graphene superlattices in a systematic way, it is desirable to control the structure parameters, which barely exist at the moment, onsite. Here, a tunable superlattice with graphene and a deformable gating structure is demonstrated. The period and duty cycle of the nano-gating, and furthermore of the superlattice potential, can be tuned through altering the shape of the gating structure with piezo-actuators, offering a tunable band structure. The tuning of the electronic band structures of both a two-dimensional and a one-dimensional superlattice is demonstrated with numerical simulations, offering a new approach for tunable electronic and photonic devices. Full article

The evaluation of Information and Communication Technology (ICT) in Education (ICTE) has become a crucial aspect in educational management. While previous attempts have been made to develop evaluation frameworks for ICTE, many existing frameworks fail to include information from multiple sources and are thus not sufficiently accurate. This study aims to address this gap by identifying core dimensions and indicators from various stakeholders in ICTE practices. Accordingly, a set of guidelines for a more comprehensive evaluation of ICTE development is generated. By applying these guidelines, a Comprehensive Evaluation Framework for ICT in Education (CEF-ICTE) is developed and validated using the Delphi methodology. The results reveal that the most pertinent dimensions for ICTE evaluation are ICT infrastructure and digital resources, followed by ICT usage, personnel support, and ICT management. Key indicators identified include the average frequency of online services utilized by students per week and the percentage of schools implementing basic data applications for management purposes. These findings underscore the importance of prioritizing certain indicators in evaluating ICTE. The present study offers a valuable tool for comprehensively assessing ICTE development and may provide policymakers with essential support for setting priorities and allocating educational resources where they are most urgently needed. Full article

G-quadruplexes (G4s) are guanine-rich non-canonical secondary structures of nucleic acids that were identified in vitro almost half a century ago. Starting from the early 1980s, these structures were also observed in eukaryotic cells, first at the telomeric level and later in regulatory regions of cancer-related genes, in regulatory RNAs and within specific cell compartments such as lysosomes, mitochondria, and ribosomes. Because of the involvement of these structures in a large number of biological processes and in the pathogenesis of several diseases, including cancer, the interest in G4 targeting has exponentially increased in the last few years, and a great number of novel G4 ligands have been developed. Notably, G4 ligands represent a large family of heterogeneous molecules that can exert their functions by recognizing, binding, and stabilizing G4 structures in multiple ways. Regarding anti-cancer activity, the efficacy of G4 ligands was originally attributed to the capability of these molecules to inhibit the activity of telomerase, an enzyme that elongates telomeres and promotes endless replication in cancer cells. Thereafter, novel mechanisms through which G4 ligands exert their antitumoral activities have been defined, including the induction of DNA damage, control of gene expression, and regulation of metabolic pathways, among others. Here, we provided a perspective on the structure and function of G4 ligands with particular emphasis on their potential role as antitumoral agents. In particular, we critically examined the problems associated with the clinical translation of these molecules, trying to highlight the main aspects that should be taken into account during the phases of drug design and development. Indeed, taking advantage of the successes and failures, and the more recent technological progresses in the field, it would be possible to hypothesize the development of these molecules in the future that would represent a valid option for those cancers still missing effective therapies. Full article