Search Results (170)

Background: Hyaluronic acid (HA) hydrogels are the most widely used injectable fillers for facial rejuvenation. A new generation of HA fillers crosslinked with poly(ethylene glycol) diglycidyl ether (PEGDE) has been developed to enhance cohesiveness, tissue integration, stability, and longevity while minimizing swelling and immunogenicity. Owing to their distinct viscoelastic properties, PEGDE-crosslinked HA fillers may require product-specific selection and adapted injection techniques. Objective: The objective of this study is to provide practical, expert-based recommendations for the safe and effective use of PEGDE-crosslinked HA hydrogels in facial aesthetic treatments. Methods: A multidisciplinary panel of nine Italian experts in aesthetic medicine, each with more than 15 years of experience using HA fillers, developed consensus recommendations based on clinical practice and available evidence. A pre-meeting questionnaire informed structured discussions during a face-to-face meeting held in Paris in January 2024. The nominal group technique was applied, with consensus defined as agreement by at least 80% of panel members. Results: Consensus was reached on product selection, injection planes, delivery devices, techniques, and typical treatment volumes for PEGDE-HA hydrogels across multiple facial regions, including the forehead, temples, midface, nasolabial folds, chin, jawline, and lips. Recommended injection techniques included microbolus, macrobolus, and retrograde linear threading, with placement ranging from superficial subcutaneous to supraperiosteal planes depending on the anatomical area and clinical indication. Typical injection volumes generally ranged from 0.1 to 0.5 mL per side. Optional ultrasound mapping was considered beneficial in selected high-risk or superficial procedures to improve anatomical safety. Conclusions: These expert consensus recommendations provide practical guidance for clinicians using PEGDE-crosslinked HA hydrogels in facial rejuvenation. Tailoring product characteristics to injection depth, technique, and regional anatomy may help optimize clinical outcomes and procedural safety. Future research priorities include prospective comparative studies with other crosslinking technologies, standardized reporting of adverse events, long-term outcome registries, and further evaluation of ultrasound-guided injection strategies. Full article

A new spiral nematode species, Scutellonema curcumae sp. n., was identified from the rhizosphere of turmeric (Curcuma longa L.) in the Western Highlands of Vietnam. Integrative taxonomical analysis, combining detailed morphology and molecular characterization (ITS, 28S D2–D3 rDNA, and COI mtDNA), confirmed its distinctiveness. Scutellonema curcumae sp. n. is characterized by a unique combination of a spiral body, a hemispherical lip region with four annuli, a robust stylet, and a rounded tail with a prominent scutellum, forming a highly divergent lineage within the genus. Beyond its description, this study reveals a significant inverse correlation between nematode population density and the phytochemical quality of the host. High infestation levels were associated with a marked decline in total curcuminoid content. Notably, lower nematode density favored a specific shift in the curcuminoid profile, with bisdemethoxycurcumin levels increasing by up to 250%. These phytochemical alterations directly influenced the therapeutic potential of the rhizomes: lower infestation levels resulted in significantly enhanced antioxidant capacity (lower SC₅₀ values) and cytotoxic activity (lower IC₅₀ against HepG2 and A549 cell lines). This work represents the first report of a Scutellonema species associated with turmeric in Vietnam and underscores its detrimental impact on the medicinal and nutraceutical value of the crop. Our findings suggest that effective nematode management is crucial not only for yield protection but as a strategic intervention in precision agriculture to optimize the secondary metabolite profiles of medicinal plants. Full article

Immune checkpoint inhibitors (ICIs), particularly PD-1/PD-L1 antibodies, have significantly improved outcomes in a variety of solid tumors, including urothelial carcinoma. However, their use is frequently associated with immune-related adverse events (irAEs) which frequently affect the skin and mucous membranes. Among these, plasma-cell-rich infiltrates are exceptionally rare. Circumorificial plasmacytosis (COP) is a rare, predominantly reactive condition typically involving mucosal transition zones, with histologic features characterized by dense, polyclonal plasma cell infiltrates and a benign clinical course. Only two case reports have described COP in association with ICI therapy and, to date, transformation or overlap with lymphoproliferative disorders such as marginal zone lymphoma has not been documented. We report the case of an 86-year-old male with urothelial carcinoma who developed a progressive, ulcerated, bleeding lesion of the lower lip during adjuvant nivolumab therapy. Histologic examination revealed a dense subepithelial infiltrate of mature plasma cells and lymphocytes. Direct and indirect immunofluorescence studies were negative, excluding autoimmune blistering disorders. Immunohistochemistry showed a predominance of CD138-positive plasma cells with a moderate kappa light-chain shift, CD19 expression, and absence of CD56, Cyclin-D1, and CD117, arguing against a plasma cell neoplasm. Molecular analysis via multiplex PCR revealed a clonal B-cell population with distinct IgH rearrangements, and some EBV-positive cells were also identified by EBER in situ hybridization. The histopathologic and molecular findings suggested a marginal zone lymphoma-like, plasmacytic proliferation arising in the setting of COP. This case illustrates a rare and diagnostically challenging constellation at the intersection of reactive and clonal B-cell proliferations in the context of ICI therapy. Although the lesion demonstrated features of clonality, the overall low B-cell content, indolent clinical course, and lack of systemic involvement support a reactive, immunodeficiency-associated lymphoproliferation rather than overt lymphoma. This case expands the known spectrum of mucocutaneous irAEs and highlights the need for careful clinicopathologic correlation, including immunophenotyping and molecular diagnostics. Awareness of such rare presentations is essential to avoid overdiagnosis and unnecessary systemic treatment in patients with otherwise indolent lesions. Full article

The pilot flame serves as the primary anchor for global flame stabilization in a centrally staged combustor. In engineering practice, it typically operates in the diffusion mode. The fuel non-uniformity and diffusion kinetics of the pilot flame may have a significant impact on the flow and flames within the combustor. The flame structure and flame–flow interaction in a centrally staged burner featuring a diffusion pilot flame are investigated in the present paper, using high-frequency CH₂O planar laser-induced fluorescence (CH₂O-PLIF), CH^* chemiluminescence, and particle image velocimetry (PIV) measurements. The stratified flame (S-flame) and the lifted flame (L-flame) are identified under two-stage conditions. The S-flame and L-flame correspond to the separated flow and the merged flow of the two stages, respectively. Significant radial oscillation of the pilot stage airflow is also found. Extensive tests demonstrate that the pilot equivalence ratio (Φp) plays an important role in flame mode switching. Silicone droplets with extremely fine sizes are introduced into the pilot fuel to trace its transportation. When the oscillating pilot stage airflow rushes towards the lip in an instant, it can entrain the pilot fuel to reach the inner side of the main stage outlet. With a low pilot fuel supply and relatively low injection velocity, the pilot fuel and the hot radicals are more likely to be entrained and accumulate in larger amounts at the inner side of the main stage outlet. Consequently, the main stage premixed mixture can be ignited at the main stage outlet, forming the S-flame. The flame mode switches from S- to L-flame when the equivalence ratio increases to the point where the corresponding velocity ratio of pilot fuel to air (V_fp/V_ap) approaches 1.0, with a reduced entrainment of the pilot fuel and radicals. Simultaneous CH₂O-PLIF and flow field results show that when the main stage is ignited downstream, hot products cannot recirculate to the pilot stage outlet, causing the extinction of the pilot flame root. This paper reveals that the fuel diffusion characteristics of the pilot stage can dramatically change the flame structure. To achieve the ideal designed flame shape, the interaction between the pilot fuel and pilot air requires very careful treatment in practical centrally staged combustors. Full article

Resveratrol (RES), a naturally occurring polyphenolic compound with well-documented anticancer potential, is limited in clinical application due to its poor aqueous solubility and low bioavailability. This study aimed to develop RES-loaded liposomes coated sequentially with chitosan (CS) and hyaluronic acid-chitosan (HA) (RES-HA-CS-Lip) to enhance RES stability, delivery, and anticancer efficacy in breast cancer cells. HA-CS-coated liposomes were prepared using a thin-film hydration technique. Their physicochemical characteristics were thoroughly investigated through dynamic light scattering, transmission electron microscopy, Fourier transform infrared spectroscopy, and differential scanning calorimetry. The optimized RES-HA-CS-Lip exhibited spherical morphology with an average particle size of 212 nm, a narrow polydispersity index (<0.4), a zeta potential of +9.04 ± 1.0 mV, and high entrapment efficiency of 82.16%. Stability studies demonstrated superior retention of size, surface charge, and encapsulation efficiency over 28 days at both 4 °C and 25 °C. In vitro release profiles at physiological and acidic pH revealed sustained drug release, with enhanced release under acidic conditions mimicking the tumor microenvironment. Antioxidant activity, assessed via DPPH and ABTS radical-scavenging assays, indicated that RES retained its radical-scavenging potential upon encapsulation. Cytotoxicity assays demonstrated markedly improved anticancer activity against MCF-7 breast cancer cells, with an IC₅₀ of 13.08 μg/mL at 48 h, while maintaining high biocompatibility toward normal HaCaT keratinocytes. RES-HA-CS-Lip demonstrated excellent stability against degradation and aggregation. Overall, these findings highlight HA-CS-coated liposomes as a promising polysaccharide-based nanocarrier that enhances stability, bioactivity, and therapeutic efficacy of RES, representing a potential strategy for targeted breast cancer therapy. Full article

Radiation-induced intestinal injury (RIII), a severe complication of abdominopelvic radiotherapy, causes intestinal ischemia, ulcers, and necrosis, severely impacting patients’ quality of life. Currently, effective treatments are limited, and a specific cure remains elusive. Our previous research showed that lactoferrin (LF) can promote intestinal stem cell (ISC) proliferation and tissue repair; however, its oral administration is limited by rapid degradation in the gastric environment. In this study, we developed LF-loaded liposomal nanoparticles (Lip-LF) using a simple ethanol injection method. The optimal formulation (cholesterol/egg yolk lecithin ratio 2:8, LF concentration 12.5 mg/mL) achieved a drug-loading capacity of 6.8% and a narrow size distribution (0.2 < PDI < 0.4). In vitro experiments demonstrated that Lip-LF protected LF from pepsin degradation in simulated gastric fluid (SGF), retaining over 80% integrity after 120 min, while releasing in simulated intestinal fluid (SIF). In vivo imaging revealed prolonged gastrointestinal retention of Lip-LF compared to free LF. In a murine model of RIII (12 Gy whole-body irradiation), Lip-LF significantly restored villus counts, increased crypt height, and promoted goblet-cell regeneration. Immunohistochemical and qPCR analyses revealed enhanced ISCs proliferation and upregulation of repair-associated genes, including Pcna and Olfm4. These findings demonstrate that Lip-LF protects LF from gastric degradation and enhances its targeted delivery to the intestine, improving its therapeutic efficacy in repairing RIII. Lip-LF thus offers a promising strategy for managing RIII. Full article

Background/Objectives: The bird cherry-oat aphid, Rhopalosiphum padi, is a major global pest of cereal crops and exhibits wing polyphenism, producing both winged (dispersive) and wingless (reproductive) morphs. Methods: To identify potential RNAi targets that could specifically disrupt the migratory winged morph, we conducted a comparative transcriptomic analysis of adult aphids. Differentially expressed genes (DEGs) were identified, annotated for their functions, and analyzed for their involvement in metabolic pathways. Results: Significant differences were observed in 121 genes between morphs: 13 were upregulated in the winged morph, while 108 were downregulated. Most DEGs were enriched in lipid metabolism and circadian rhythm pathways, suggesting that wing polymorphism may be adaptively linked to energy resource allocation strategies. Conclusions: This study firstly reveals the adult-stage-specific regulatory roles of lipid metabolism and circadian rhythm pathways in wing polyphenism, identifying six candidate genes (BCORL1, AMP-L, Pfl, Lip3L, HLFL(X7), and HLFL(X4)) for RNAi-based biocontrol strategies targeting migratory morphs. Full article

White-lipped tree frogs, Polypedates braueri, are currently included in the list of terrestrial wildlife with important ecological, scientific, and social value in China. Understanding the structure and characteristics of the mitochondrial genome provides essential information for resource conservation and phylogenetic analyses of P. braueri. While the complete mitochondrial genomes serve as important molecular markers for phylogenetic and genetic studies, the mitochondrial genome of P. braueri has received little attention. In this paper, we analyzed the characterization of the mitochondrial genome of P. braueri and investigated the phylogenetic relationships of Rhacophoridae. The complete mitochondrial genome of P. braueri was 20,254 bp in length, containing thirty-six genes (twelve protein-coding genes (PCGs), two ribosomal RNA genes (rRNAs), twenty-two transfer RNA genes (tRNAs)), three non-coding regions for the origin of light strand (O_L), and two control regions (CR). There were six overlapping regions and seventeen intergenic spacer regions in the mitogenome. The mitogenome also showed a bias towards A + T content (61.87%) and had negative AT-skew (−0.039) and GC-skew (−0.209). All the PCGs employed the ATG, ATA, or ATT as the start codon and TAA, TAG, AGG, or single T as the stop codon. Additionally, all of the tRNAs displayed a typical cloverleaf secondary structure, except trnS1, which lacked the D arm. The phylogenetic analysis, based on the maximum likelihood (ML) and Bayesian inference (BI) methods, revealed that Rhacophoridae could be classified into four monophyletic genera. The phylogenetic status of P. braueri was closely related to that of Polypedates megacephalus and Polypedates leucomystax. Additionally, selective pressure analysis suggested that COX1 and ND1 were highly efficient for discriminating closely related species in the genus Polypedates, while ND4L was the most appropriate marker for population-level genetic analyses. The diversification of the Polypedates commenced during the Late Oligocene and extended into the Miocene. The present study provides valuable genomic information on P. braueri and new insights into the phylogenetic relationships of Rhacophoridae. Full article

Background: Based on our previous study, Celastrol-based proteolysis-targeting chimeras (Celastrol-PROTACs) were shown to induce apoptosis in 4T1 cells by selectively degrading GRP94 and CDK1/4 through the endogenous ubiquitin–proteasome system. However, their clinical translation is limited by poor solubility, low targeting efficiency, and liver and kidney toxicity. Methods: To address these limitations, we developed a pegylated liposomal formulation of Celastrol-PROTACs (Lip-Celastrol-PROTACs) and evaluated its therapeutic efficacy and safety profile. Results: The tumor volume of the mice in the Celastrol-PROTACs solution group (286 ± 79 mm³) was significantly larger than that of those in the Lip-Celastrol-PROTACs group (229 ± 49 mm³) on day 18 after intravenous administration (p < 0.01). This difference between the two groups was statistically significant (p < 0.01). Notably, the Celastrol-PROTACs group exhibited significantly greater weight loss compared to the Lip-Celastrol-PROTACs group (p < 0.001). In vivo toxicity assessments revealed that the levels of AST and BUN in the Celastrol-PROTACs group were 27.93 ± 4.88 U/L and 12.36 ± 1.33 μmol/L, respectively, whereas those in the Lip-Celastrol-PROTACs group were found to be 7.92 ± 0.94 U/L and 8.19 ± 0.67 μmol/L, respectively. These findings indicate a statistically significant difference between the two formulations (p < 0.01). Conclusions: Our research demonstrated that pegylated liposomes could improve the targeting efficiency and minimize the toxicity of PROTACs, thereby improving overall therapeutic efficacy. These findings indicated that Lip-Celastrol-PROTACs represent a promising strategy for future clinical applications. Full article

Guinea pigs (Cavia porcellus) are bred as livestock in South American countries from the Andean region, including Ecuador. Despite their importance for the local rural economy, no public health management guidelines have ever been implemented for guinea pig farming. Moreover, several reports have shown the carriage of diverse zoonotic pathogens in livestock guinea pigs, including respiratory and enteric pathogens, or Toxoplasma gondii. Leptospirosis, a zoonotic disease caused by bacteria from Leptospira genus, is endemic in Ecuador and has multiple animal reservoirs, with rodents considered to be the main vector for transmission to humans. However, the role of livestock guinea pigs in the epidemiology of leptospirosis is poorly understood. In this study, the prevalence of antibodies against Leptospira in guinea pigs from Ecuador was analyzed with the Microaglutiantion Test (MAT). Moreover, the shedding of Leptospira by backyard livestock guinea pigs was also addressed, analyzing fecal and urine samples by qPCR for lipL32, secY and rrs genes. From the 118 guinea pigs analyzed by MAT, 61.9% were positive for 19 different pathogenic serovars, with Icterohaemorrhagiae, Pomona, Castellonis and Bataviae being the most prevalent ones. From the 231 urine samples and 225 fecal samples collected, 27.7% and 78.7% were positive for Leptospira by qPCR, respectively. Our results highlight the role of livestock guinea pigs as a reservoir for leptospirosis. Moreover, this study underscores the zoonotic threat associated with the shedding of Leptospira within households in rural communities where guinea pigs are bred as livestock. Animal and public health guidelines from a One Health perspective must be implemented to prevent leptospirosis transmission from guinea pigs in Ecuador and other countries in the Andean Region where the breeding of backyard livestock guinea pigs is common. Full article

This exploratory study investigates the usability of performance metrics for generative adversarial network (GAN)-based models for speech-driven facial animation. These models focus on the transfer of speech information from an audio file to a still image to generate talking-head videos in a small-scale “everyday usage” setting. Two models, LipGAN and a custom implementation of a Wasserstein GAN with gradient penalty (L1WGAN-GP), are examined for their visual performance and scoring according to commonly used metrics: Quantitative comparisons using FID, SSIM, and PSNR metrics on the GRIDTest dataset show mixed results, and metrics fail to capture local artifacts crucial for lip synchronization, pointing to limitations in their applicability for video animation tasks. The study points towards the inadequacy of current quantitative measures and emphasizes the continued necessity of human qualitative assessment for evaluating talking-head video quality. Full article

Background: Children affected by unilateral cleft lip and palate (UCLP) represent a therapeutic challenge requiring the development of novel therapies, such as the implant of a bioengineered tissue—BIOCLEFT—or the use of nasoalveolar molding (NAM). The objective of this work was to evaluate the effects of NAM on the surgical and aesthetic outcomes of children with UCLP. Methods: A total of 36 children with UCLP treated at a craniofacial malformations management unit were evaluated, including 23 patients treated with presurgical NAM followed by palate surgical correction (NAM group) and 13 patients treated surgically without previous NAM (non-NAM group). Measurements were obtained from each patient immediately before palate surgery, including four linear measurements: nasal ala projection length (NAPL), nasal dome height (NDH), superoinferior alar groove position (S-I AGP), and nasal dome position (M-L NDP), and two angular measurements: columellar deviation (CD) and nasal bridge deviation (NBD). Results: When NAM was used, a significant improvement of the basilar view linear measurements of the patient’s nose was found, including the NAPL and NDH, and the frontal view linear measurement M-L NDP, but not S-I AGP. Significant improvements were also observed in the angular measurements of nasal symmetry CD and NBD. All these variables, except the S-I AGP, significantly correlated with the treatment group, and two variables—NAPL and CD—significantly contributed to generate a predictive model developed using binary logistic regression. Conclusions: These findings support the use of NAM to efficiently improve the nasal symmetry and the presurgical outcomes of patients with UCLP. Full article

Background: The present study investigated the relation between dental inclination, colorimetric variation, and aesthetic perception according to the modification of incisor inclination. Smile aesthetics, shaped by morphological factors and patient perception, are vital for social attractiveness and treatment success. This study aimed to assess the effect of varying head tilt on the perceived colour of upper central incisors by simulating changes in torque of the tooth, as well as evaluate factors influencing the perception of an aesthetic smile, including morphological characteristics and gingival aesthetic parameters. Methods: The study was comprised of three stages: colour analysis, evaluation of micro- and mini-aesthetic smile features, and an image-based assessment to determine evaluator perceptions and overall smile attractiveness. A sample of 50 students with complete, lesion-free anterior dentition was analysed. To simulate the effect of orthodontic torque changes during colour analysis, subjects tilted their heads downward and upward, representing palatal and buccal crown torque, respectively. Standardized macro-intraoral photographs were captured under controlled lighting conditions using a DSLR camera stabilized on a tripod in the different positions: the neutral head position (p0), 15° upward (p + 15), and 15° downward (p − 15). Digital colour analysis was conducted in the CIELAB colour space (L*, a*, b*). In the next stage, focusing on micro- and mini-aesthetic evaluation, an additional 50 smiles were generated using artificial intelligence via the SmileCloud program—one digitally enhanced smile per subject—complementing the initial set of 50 spontaneous smiles. These 100 smile images were evaluated by 50 laypersons and 50 dentists using a visual analogue scale via an online questionnaire, in order to assess perceptions, determine smile attractiveness, and quantify gingival aesthetic parameters. Results: The statistically significant regression results are as follows: those for the L* values in all three head inclinations: downward (−15 degrees), upward (+15 degrees), and total tilting (−15 to +15 degrees), as well as for the a* values for downward tilting and the b* values for total tilting. When the head is tilted downwards, the central incisors are positioned retrusively, and the L* b* values reveal a darker and more yellowish appearance, whereas, with the head tilted upwards, the central incisors protrude, and L* a* values indicate a brighter and more greenish appear. In the evaluation stage of the smile aesthetics study, no significant differences were observed in the judgments between laypersons and dentists or between males and females. Smiles with a high or average anterior line, parallel arc, upward lip curvature, visible first/second premolars, a smile index of 5.08–5.87, and symmetry score of 1.04 were rated as more attractive. Significant asymmetries were observed between upper dental hemi-quadrants in gingival contour and interdental papilla height, highlighting subtle morphological variations relevant to smile aesthetics. Conclusions: Aesthetic assessment revealed that the findings suggest a measurable impact of head position on dental colour perception and aesthetic evaluation. Evaluator variables including profession and gender exerted negligible effects on aesthetic perception, whereas smile attractiveness features and gingival aesthetic parameters demonstrate significant clinical applicability in patient management. Full article

Adenosine signaling plays protective roles in gingival mitochondrial health and inflammation control, with the ectoenzyme CD73 implicated in periodontitis. Here, we investigated the effects of selective adenosine A2a receptor (A2aR) stimulation using the agonist CGS21680 in a mouse model of ligature-induced periodontitis (LIP) and in gingival fibroblast mitochondrial function. Mature C57Bl/6 mice underwent LIP and received daily intraperitoneal injections of CGS21680 (0.1 mg/Kg) or saline. After 8 days, gingival tissues and maxillae were analyzed for alveolar bone loss and Il-1β levels. In parallel, murine gingival fibroblasts (mGFs) were treated with Tnf-α (5 ng/mL) ± CGS21680 (10 µM) to assess mitochondrial function, morphology, and quality control. A2aR activation significantly reduced alveolar bone loss and Il-1β expression in vivo. In vitro, CGS21680 suppressed Tnf-α-induced Cxcl10 and Cxcl12 expressions and enhanced Vegf production. Mitochondrial analysis revealed increased mitochondrial complex levels, membrane potential, and mass, alongside reduced reactive oxygen species (ROS), proton leak, and mitochondrial stress. Ultrastructural studies showed elongated, healthier mitochondria and increased pro-fusion markers, indicating enhanced mitochondrial quality control. Overall, A2aR stimulation attenuates periodontal inflammation and confers mitoprotective effects on gingival fibroblasts, supporting its potential as a therapeutic strategy to both mitigate periodontitis progression and preserve tissue bioenergetics supporting cellular resilience. Full article

The optimization of bioactive compound mixtures is critical for enhancing pharmacological efficacy. This study investigates, for the first time, the combined effects of eugenol, camphor, and terpineol, focusing on their half-maximal inhibitory concentrations (IC₅₀) across multiple biological responses related to diabetes management. Using a mixture design approach, the objective was to determine the optimal formulation that maximizes bioactivity and validate the findings experimentally. A simplex-centroid design was applied to evaluate the combined effects of eugenol, camphor, and terpineol on AAI _IC50, AGI _IC50, LIP _IC50, and ALR _IC50 responses. The desirability function was used to determine the ideal composition. The optimized formulation was experimentally validated using in vitro assays, and IC50 values were measured for each response using standard protocols. Results: The optimal formulation identified was 44% eugenol, 0.19% camphor, and 37% terpineol, yielding IC₅₀ values of 10.38 µg/mL (AAI), 62.22 µg/mL (AGI), 3.42 µg/mL (LIP), and 49.58 µg/mL (ALR). The desirability score (0.99) confirmed the effectiveness of the optimized blend. Experimental validation of the optimal mixture resulted in IC₅₀ values of 11.02 µg/mL (AAI), 60.85 µg/mL (AGI), 3.75 µg/mL (LIP), and 50.12 µg/mL (ALR), showing less than 10% deviation from predicted values, indicating high model accuracy. This study confirms the combined potential of eugenol, camphor, and terpineol, with eugenol and terpineol significantly enhancing bioactivity. The validated formulation demonstrates potential for pharmaceutical and cosmeceutical applications. Future research should explore mechanistic interactions, bioavailability, and in vivo efficacy to support the development of optimized natural compound-based therapies. Full article