ENGOT-en11/GOG-3053/KEYNOTE-B21: A Randomised, Double-Blind, Phase 3 Study of Pembrolizumab or Placebo Plus Adjuvant Chemotherapy With or Without Radiotherapy in Patients With Newly Diagnosed, High-Risk Endometrial Cancer.

BACKGROUND: Pembrolizumab plus chemotherapy provides clinically meaningful benefit as first-line therapy for advanced (locoregional extension and residual disease after surgery)/metastatic/recurrent pMMR and dMMR endometrial cancer (EC), with greater magnitude of benefit in the dMMR phenotype. We evaluated addition of pembrolizumab to adjuvant chemotherapy (with/without radiation therapy) among patients with newly-diagnosed, high-risk EC without any residual macroscopic disease following curative-intent surgery. METHODS: Patients with histologically confirmed high-risk (FIGO stage I/II of non-endometrioid histology or endometrioid histology with p53/TP53 abnormality, or stage III/IVA of any histology) EC following surgery with curative intent and no evidence of disease postoperatively, with no prior radiotherapy or systemic therapy. Patients were randomised to pembrolizumab 200mg or placebo Q3W for 6 cycles added to carboplatin-paclitaxel followed by pembrolizumab 400mg or placebo Q6W for 6 cycles per treatment assignment. Radiotherapy was at the investigator's discretion. Primary endpoints were investigator-assessed disease-free survival (DFS) and overall survival in the intention-to-treat population. RESULTS: 1095 patients were randomised (pembrolizumab, n=545; placebo, n=550). At this interim analysis (data cutoff, 4-March2024), 119 (22%) DFS events occurred in the pembrolizumab group and 121 (22%) occurred in the placebo group (hazard ratio, 1.02 [95% CI, 0.79‒1.32]; P=0.570). Kaplan-Meier estimates of 2-year DFS rates were 75% and 76% in the pembrolizumab and placebo groups, respectively. The hazard ratio for DFS was 0.31 (95% CI, 0.14‒0.69) in the dMMR population (n=281) and 1.20 (95% CI, 0.91‒1.57) in the pMMR population (n=814). Grade ≥3 adverse events (AEs) occurred in 386 of 543 (71%) and 348 of 549 (63%) patients in the pembrolizumab and placebo groups, respectively. No treatment-related grade 5 AEs occurred. CONCLUSION: Adjuvant pembrolizumab plus chemotherapy did not improve DFS in patients with newly-diagnosed, high-risk, all-comer EC. Preplanned subgroup analyses for stratification factors suggests pembrolizumab plus chemotherapy improved DFS in patients with dMMR tumours. Safety was manageable.

The ancestral environment of teosinte populations shapes their root microbiome.

BACKGROUND: The composition of the root microbiome affects the host's growth, with variation in the host genome associated with microbiome variation. However, it is not known whether this intra-specific variation of root microbiomes is a consequence of plants performing targeted manipulations of them to adapt to their local environment or varying passively with other traits. To explore the relationship between the genome, environment and microbiome, we sampled seeds from teosinte populations across its native range in Mexico. We then grew teosinte accessions alongside two modern maize lines in a common garden experiment. Metabarcoding was performed using universal bacterial and fungal primers to profile their root microbiomes. RESULTS: The root microbiome varied between the two modern maize lines and the teosinte accessions. We further found that variation of the teosinte genome, the ancestral environment (temperature/elevation) and root microbiome were all correlated. Multiple microbial groups significantly varied in relative abundance with temperature/elevation, with an increased abundance of bacteria associated with cold tolerance found in teosinte accessions taken from high elevations. CONCLUSIONS: Our results suggest that variation in the root microbiome is pre-conditioned by the genome for the local environment (i.e. non-random). Ultimately, these claims would be strengthened by confirming that these differences in the root microbiome impact host phenotype, for example, by confirming that the root microbiomes of high-elevation teosinte populations enhance cold tolerance.

Hereditary haemochromatosis: Prevalence and characterization of the disease in a tertiary hospital in Aragon.

BACKGROUND: The main genetic cause of iron overload is haemochromatosis (HC). In recent years, the study of non-HFE genes (HFE2, HJV, HAMP, TRF2, SLC40A1, and BMP6) has become relevant thanks to next-generation sequencing (NGS) and multiplex ligation-dependent probe amplification (MLPA) techniques. Our objectives were to estimate the prevalence of both HFE (C282Y/HY63D variants) and non-HFE variants attending a tertiary hospital in Aragón, to predict the effect of the variants on the protein, and to establish a genotype-phenotype correlation evaluating with the clinical context. METHODS: Retrospective descriptive study from 2006 to 2020 of patients attended at genetic consultation in a reference hospital for HC in Aragon. We calculated prevalence of HFE and non-HFE variants. We analysed non-HFE genes (HFE2, HJV, HAMP, TRF2, SLC40A1, and BMP6), used bioinformatics tools, consulted different databases and measured clinical parameters (laboratory and imaging). RESULTS: The prevalence of C282Y homozygous was 5.95% respect the total of cases and 0.025% respect our population. The prevalence of non-HFE HC variants was 1.94% respect the total of cases and 0.008% respect our population. We found 27 variants in non-HFE genes and 4 in HFE gene, of which 6 were classified as variant of uncertain clinical significance (VUS), or likely pathogenic or pathogenic according to the ACMG classification criteria. CONCLUSION: Our prevalence results are as expected, and similar to those obtained by other studies. Although some of the genetic findings explain the clinical symptoms of some of our patients, we remain have a high number of patients without a clear molecular diagnosis.

Generation of functional neurons from adult human mucosal olfactory ensheathing glia by direct lineage conversion.

A recent approach to promote central nervous system (CNS) regeneration after injury or disease is direct conversion of somatic cells to neurons. This is achieved by transduction of viral vectors that express neurogenic transcription factors. In this work we propose adult human mucosal olfactory ensheathing glia (hmOEG) as a candidate for direct reprogramming to neurons due to its accessibility and to its well-characterized neuroregenerative capacity. After induction of hmOEG with the single neurogenic transcription factor NEUROD1, the cells under study exhibited morphological and immunolabeling neuronal features, fired action potentials and expressed glutamatergic and GABAergic markers. In addition, after engraftment of transduced hmOEG cells in the mouse hippocampus, these cells showed specific neuronal labeling. Thereby, if we add to the neuroregenerative capacity of hmOEG cultures the conversion to neurons of a fraction of their population through reprogramming techniques, the engraftment of hmOEG and hmOEG-induced neurons could be a procedure to enhance neural repair after central nervous system injury.

Intestinal Fatty Acid Binding Protein as a Predictor of Early Mesenteric Injury Preceding Clinical Presentation: A Case Report.

Introduction: Diagnosing non-occlusive mesenteric ischaemia (NOMI) in patients is complicated, due to poor signs and symptoms and non-specific laboratory tests, leading to a high mortality rate. This case study presents the rare case of a patient who developed mesenteric ischaemia after an emergency thoracic endovascular aneurysm repair (TEVAR) for a type B aortic dissection (TBAD) and peri-operative cardiogenic shock. Study outcomes revealed that intestinal fatty acid binding protein (I-FABP) identified early mucosal damage two days before the clinical presentation. Report: A 43 year old male patient was admitted to the emergency department with an acute TBAD and a dissection of the superior mesenteric artery (SMA), for which TEVAR was performed with additional stent placement in the SMA. Peri-operatively, the patient went into cardiogenic shock with a sustained period of hypotension. Post-operatively, the plasma I-FABP levels were measured prospectively, revealing an initial increase on post-operative day five (551.1 pg/mL), which continued beyond day six (610.3 pg/mL). On post-operative day seven, the patient developed a fever and demonstrated signs of peritonitis and bowel perforation. He underwent an emergency laparotomy, followed by an ileocaecal resection (<100 cm) with a transverse ileostomy. Pathological analysis confirmed the diagnosis of mesenteric ischaemia. Discussion: The diagnosis of NOMI in critically ill patients is often complicated, and the currently available diagnostic markers lack the specificity and sensitivity to detect early intestinal injury. This case report highlights that elevated I-FABP in plasma levels may indicate the presence of early mesenteric injury. Further research needs to be conducted before I-FABP can be applied in daily practice.

Physical separation and reduction of contact duration with sexually hyperactive bucks decrease testosterone concentrations and sexual behaviour in bucks in sexual rest.

Sexually hyperactive bucks are more efficient than sexually hypoactive bucks in stimulating testosterone secretion and sexual behaviour in other bucks in seasonal sexual rest by the phenomenon that we called the "buck-to-buck effect". Here, we determined whether physical separation and reduction of the duration of contact with the sexually hyperactive bucks would modify those parameters in sexually hypoactive bucks exposed to the "buck-to-buck effect". Bucks were subjected to natural day length throughout the study; this was the sexually hypoactive group. Other bucks were subjected to artificial long days (16 h of light per day) from 15 November to 15 January followed by exposure to natural day length to stimulate their sexual activity during the rest season; this was the sexually hyperactive group. In Experiment 1, we determined testosterone concentrations and sexual behaviour of six sexually hypoactive bucks separated 1.5 m from six sexually hyperactive bucks for 60 days by a metal open work fence, while a control group of six sexually hypoactive bucks was in permanent contact with six sexually hyperactive bucks. In Experiment 2, the duration of contact with sexually hyperactive males was reduced from 31 days (contact group, six bucks) to 10 days (withdraw group, seven bucks). In experiments 1 and 2, there was an effect of time (P < 0.01) and an interaction between time and groups (P < 0.05). In Experiment 1, testosterone plasma concentrations were greater in bucks in contact with sexually hyperactive bucks than in those separated from bucks at 20 and 30 days after the introduction of sexually hyperactive bucks (P < 0.01). The bucks from the contact group also displayed more nudging than bucks from the separated group from 0 to 30 days (P < 0.001). In Experiment 2, testosterone concentrations were greater in the contact group than in those from the withdraw group from 19 to 31 days after the introduction of sexually hyperactive bucks (P < 0.05). Bucks from the withdraw group displayed more nudging than the contact group 7 days after the introduction of the sexually hyperactive bucks (P < 0.05). Afterwards, bucks from the contact group displayed more nudging than the withdraw group 14, 21 and 28 days after the introduction of the sexually hyperactive bucks. We concluded that physical separation and reduction of the duration of contact with the sexually hyperactive bucks decrease testosterone concentrations and sexual behaviour of bucks in sexual rest exposed to the "buck-to-buck effect".

The Diagnostic Value of Biomarkers in Acute Mesenteric Ischaemia Is Insufficiently Substantiated: A Systematic Review.

OBJECTIVE: There is an urgent need for accurate biomarkers to support timely diagnosis of acute mesenteric ischaemia (AMI) and thereby improve clinical outcomes. With this systematic review, the aim was to substantiate the potential diagnostic value of biomarkers for arterial occlusive AMI. DATA SOURCES: The Pubmed, Embase, and the Cochrane Library electronic databases were searched. REVIEW METHODS: A systematic review of the literature has been conducted to define the potential diagnostic value of biomarkers for arterial occlusive AMI. All studies including ≥ 10 patients describing biomarkers for macrovascular occlusive AMI between 1950 and 17 February 2023 were identified within the Pubmed, Embase, and the Cochrane Library electronic databases. There were no restrictions to any particular study design, but letters and editorials were excluded. The QUADAS-2 tool was used for the critical appraisal of quality. The study protocol was registered on Prospero (CRD42021254970). RESULTS: Fifty of 4334 studies were eligible for inclusion in this review. Ninety per cent of studies were of low quality. A total of 60 biomarkers were identified, with 24 in two or more studies and 15 in five or more studies. There was variation in reported units, normal range, and cut off values. Meta-analysis was not possible due to study heterogeneity. Biomarkers currently recommended by the European Journal of Vascular and Endovascular Surgery, European Society for Trauma and Emergency Surgery 2016, and World Society of Emergency Surgery 2017 guidelines also had heterogeneous low quality data for use in the diagnosis of AMI. CONCLUSION: This systematic review demonstrates high heterogeneity and low quality of the available evidence on biomarkers for arterial occlusive AMI. No clinical conclusions can be drawn on a biomarker or combination of biomarkers for patients suspected of arterial occlusive AMI. Restraint is advised when rejecting or determining AMI solely based on biomarkers.

"They Protect us as if they were our Mom" Masking Attitudes from Freelist Survey Data and Qualitative Interviews in San Diego School Communities.

BACKGROUND: Despite being disproportionately impacted by COVID-19 due to a lack of structural support, marginalized communities have been largely ignored in the politically polarized debate over school masking. In response to this, we sought to explore masking attitudes by centering the voices of parents and children at historically marginalized, predominantly Hispanic schools in southern California. METHODS: We conducted a mixed-methods study with parents and children attending 26 low-income predominantly Hispanic-serving elementary schools. A random sample of parents was asked to provide a freelist of words they associate with masking. A subset of parents with children aged 4-6 was recruited from these surveys to participate in parent-child interviews (PCI). We calculated Smith's salience index for all unique items, stratifying by language (English/Spanish). Item salience guided PCI thematic analysis for additional context and meaning. RESULTS: 648 participants provided 1118 unique freelist items in English and Spanish. 19 parent-child pairs were interviewed, 11 in Spanish and 8 in English. The most salient words were "safety"(0.37), "protection"(0.12), "prevention"(0.05), "health"(0.04), "good"(0.03), "can't breathe"(0.03), "necessary"(0.02), "care"(0.02), "precaution"(0.02), and "unnecessary"(0.02). Spanish speakers had a more favorable view of masking than English speakers, particularly regarding "protection" (0.20 vs 0.08) and "prevention" (0.10 vs 0.02). DISCUSSION: Masking is an affordable individual-level risk mitigation that protects the communities that have inequitably shouldered the burdens of the COVID-19 pandemic. We recommend that policymakers prioritize the views of those most impacted when deciding on risk mitigation policies like school masking.

Evaluation of online learning readiness in the new distance learning normality.

The COVID-19 pandemic influenced teaching and learning in higher education. The transformation towards digital education challenged Faculty and students. This research examines the online learning readiness of students in a Higher Education Institution in Mexico. Specifically, we investigated how much prior digital skills, as well as having used the digital resources available by the university, influenced their academic achievement in distance learning settings. Seven dimensions of online learning readiness were selected to evaluate the student's preparation for the online learning process. Questionnaires were applied before the start and at the end of digital courses. Follow-up tools were offered to support the student, and two groups were observed, users and non-users of the digital devices. It was observed that students who used the support developed significantly better critical thinking, problem-solving, and time organization skills than non-users. On the other hand, although the evaluations were not significantly different, the lowest averages were found in the non-user group. Our results indicate that prior training in the use of digital tools is essential for the success of online education; in the same way, a timely follow-up with technical and pedagogical assistance is necessary for developing competencies. Training more autonomous and independent students capable of distance learning in a global world demands experts in digital education urgently. Educational institutions must embrace new technologies and teaching methods to meet the ever-changing needs of students. This research is expected to play a crucial role in promoting constructive discussions and facilitating informed decisions concerning the creation of future educational models.

Influence of plasma kinetic energy during the pulsed laser deposition of borophene films on silicon (100).

Developing borophene films with good structural stability on non-metallic substrates to maximize their potential in photosensitivity, gas detection, photothermia, energy storage, and deformation detection, among others has been challenging in recent years. Herein, we succeeded in the pulsed laser deposition of multilayered borophene films on Si (100) with ß12 or χ3 bonding by tuning the mean kinetic energy in the plasma during the deposition process. Raman and X-ray photoelectron spectroscopies confirm ß12 and χ3 bonding in the films. Borophene films with ß12 bonding were obtained by tuning a high mean kinetic energy in the plasma, while borophene with χ3 bonding required a relatively low mean kinetic energy. Atomic force microscopy (AFM) micrographs revealed a granular and directional growth of the multilayered borophene films following the linear atomic terraces from the (100) silicon substrate. AFM nanofriction was used to access the borophene surfaces and to reveal the pull-off force and friction coefficient of the films where the surface oxide showed a significant contribution. To summarize, we show that it is possible to deposit multilayered borophene thin films with different bondings by tuning the mean kinetic energy during pulsed laser deposition. The characterization of the plasma during borophene deposition accompanies our findings, providing support for the changes in kinetic energy.

Mycorrhizal status and host genotype interact to shape plant nutrition in field grown maize (Zea mays ssp. mays).

Arbuscular mycorrhizal fungi (AMF) establish symbioses with the major cereal crops, providing plants with increased access to nutrients while enhancing their tolerance to toxic heavy metals. However, not all plant varieties benefit equally from this association. In this study, we used quantitative trait loci (QTL) mapping to evaluate the combined effect of host genotypic variation (G) and AMF across 141 genotypes on the concentration of 20 mineral elements in the leaves and grain of field grown maize (Zea mays spp. mays). Our mapping design included selective incorporation of a castor AMF-incompatibility mutation, allowing estimation of AMF, QTL and QTLxAMF effects by comparison of mycorrhizal and non-mycorrhizal plants. Overall, AMF compatibility was associated with higher concentrations of boron (B), copper (Cu), molybdenum (Mo), phosphorus (P), selenium (Se) and zinc (Zn) and lower concentrations of arsenic (As), iron (Fe), magnesium (Mg), manganese (Mn), potassium (K) and strontium (Sr). In addition to effects on individual elements, pairwise correlation matrices for element concentration differed between mycorrhizal and non-mycorrhizal plants. We mapped 22 element QTLs, including 18 associated with QTLxAMF effects that indicate plant genotype-specific differences in the impact of AMF on the host ionome. Although there is considerable interest in AMF as biofertilizers, it remains challenging to estimate the impact of AMF in the field. Our design illustrates an effective approach for field evaluation of AMF effects. Furthermore, we demonstrate the capacity of the ionome to reveal host genotype-specific variation in the impact of AMF on plant nutrition.

Nicotinamide, an acetylcholinesterase uncompetitive inhibitor, protects the blood‒brain barrier and improves cognitive function in rats fed a hypercaloric diet.

Oxidative stress and inflammation induced by abundant consumption of high-energy foods and caloric overload are implicated in the dysfunction of the blood‒brain barrier (BBB), cognitive impairment, and overactivation of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). These enzymes hydrolyse acetylcholine, affecting anti-inflammatory cholinergic signalling. Our aim was to evaluate whether nicotinamide (NAM) attenuates the impairment of the BBB and cognitive function, improving cholinergic signalling. Forty male rats were distributed into five groups: one group was fed a standard diet, and the remaining groups were fed a high-fat diet and a beverage with 40% sucrose (HFS; high-fat sucrose). In three of the HFS groups, the carbohydrate was replaced by drinking water containing different concentrations of NAM for 5 h every morning for 12 weeks. The biochemical profile, levels of stress and inflammation markers, cholinesterase activities, BBB permeability, and cognitive capacity were evaluated. The results showed that the HFS diet disturbed the metabolism of carbohydrates and lipids, causing insulin resistance. Simultaneously, AChE and BChE activities, levels of proinflammatory cytokines, oxidation of proteins and lipoperoxidation increased along with decreased antioxidant capacity in serum. In the hippocampus, increased activity of cholinesterases, protein carbonylation and lipoperoxidation were associated with decreased antioxidant capacity. Systemic and hippocampal changes were reflected in increased BBB permeability and cognitive impairment. In contrast, NAM attenuated the above changes by reducing oxidative stress and inflammation through decreasing cholinesterase activities, especially by uncompetitive inhibition. NAM may be a potential systemic and neuroprotective agent to mitigate cognitive damage due to hypercaloric diets.

Conocimiento de las puérperas sobre los efectos perinatales del tabaquismo materno y factores sociodemográficos asociados al consumo / Knowledge of puerperal women about the effects rates of maternal smoking and factors sociodemographics associated with consumption

Objetivo. El tabaquismo materno es un factor de riesgo conductual, evitable y cuyos efectos perjudiciales alcanzan todo el ciclo vital del niño. El objetivo es valorar el conocimiento de una población de puérperas atendidas en el Hospital de la Línea de la Concepción, sobre los efectos perinatales del tabaquismo materno. Material y métodos. Estudio exploratorio, transversal (septiembre a noviembre de 2022). Muestreo consecutivo y aplicación de encuesta a 151 puérperas/ expedientes de neonatos, para recolectar información sociodemográfica, clínica obstétrica y del neonato, de consumo de tabaco y de conocimiento sobre efectos perinatales del tabaquismo materno con preguntas cerradas. Estadísticas descriptivas y comparación de grupos independientes con las pruebas t de Student y chi-cuadrado. Resultados. El consumo de tabaco previo al embarazo distinguió un 32% (48/151) de fumadoras. Se obtuvo un nivel global de aciertos entre el 45% y el 76,8%; mayor proporción de aciertos entre no fumadoras (rango 45,6-79,6%) que entre fumadoras (rango 37,5-72,9%). Para cada enunciado, el nivel de aciertos resultó sin diferencias (p>0,05) entre ambos grupos. Conclusiones. El nivel de conocimientos registrado no mostró diferencias entre fumadoras y no fumadoras. Se discuten alternativas para profundizar en la investigación y acciones integrales orientadas a reducir y eliminar el consumo de tabaco por la población femenina general y las mujeres embarazadas. (AU)

Objective. Maternal smoking is an avoidable behavioral risk factor whose harmful effects reach the entire life cycle of the child. The objective is to evaluate the knowledge of a population of puerperal women treated at the Hospital de la Linea de la Concepción (Cádiz, Spain), about the perinatal effects of maternal smoking. Material and methods. Exploratory, cross-sectional study –September to November 2022. Consecutive sampling and survey application to 151 puerperal women/newborn records, to collect sociodemographic, obstetric, and neonatal clinic information on tobacco use and knowledge about the perinatal effects of maternal smoking with closed questions. Descriptive statistics and comparison of independent groups with Student’s t and chi-square tests. Results . Tobacco use prior to pregnancy distinguished 32% (48/151) smokers. A level global of hits between45% and 76.8% was obtained; higher proportion of correct answers among non-smokers (range 45.6%-79.6%) than among smokers (range 37.5%-72.9%). For each statement, the level of correct answers was not different between both groups (p>0.05). Conclusions. The level of knowledge registered did not show differences between smokers and non-smokers. Alternatives are discussed to deepen the research and integral actions aimed at reducing and eliminating tobacco use by the general female population and pregnant women. (AU)

First steps to study the demography of vascular epiphytes in cities.

Urban ecosystems could jeopardize the existence of vascular epiphytes (VE) given that their occurrence is linked to phorophyte availability and particular climatic conditions. Despite reports of VE in cities, nothing is known about their demography. A first step in this direction is to describe their population structures (PS). We established the PS of VE present in urban parks in Oaxaca City (Mexico), addressing the following questions: 1) what is their demographic status? and 2) are there differences in the structure of populations growing in native versus exotic phorophytes? During 2021, we censused all the trees in six urban parks, recording their origin (native or exotic), the epiphytic species found on them and the development stages present in each VE population. Overall, five VE species were documented: Tillandsia ionantha, T. makoyana, T. sp., T. schiedeana and T. recurvata (Bromeliaceae); the first three with only one individual and the latter two with 95 and 5,694, respectively. A MANOVA test indicated significant differences in PS between T. recurvata (type I structure, suggesting a growing population) and T. schiedeana (type III structure, suggesting a senile population) (Wilkes' λ= 0.821, F-Radio= 11.96 P<0.001). PS showed no differences related to tree origin. Our results indicate that it is necessary to conduct demographic studies to have a more accurate idea of the current condition of vascular epiphytes in cities. For instance, even though we found five VS species, only one of them seems to have viable populations in Oaxaca city.

Concurrent optical inspection to boost characterization of plastic cortical bone under mechanical deformation.

The simultaneous surface and internal measurements from a chemically modified cortical bovine bone suffering a plastic range deformation are presented. Since the bone is an anisotropic structure, its mechanical response could be modified if its organic or inorganic phases change. The latter could result in high plastic deformations, where the interferometrical signal from an optical analysis is easily de-correlated. In this work, digital holography interferometry (DHI) and Fourier domain optical coherence tomography (FD-OCT) are used to analyze the plastic range deformation of the bone under compression. The simultaneous use of these two optical methods gives information even when one of them de-correlates. The surface results retrieved with DHI show the high anisotropy of the bone as a continuously increasing displacement field map. Meanwhile, the internal information obtained with FD-OCT records larger deformations at different depths. Due to the optical phase, it is possible to complement the measurements of these two methods during the plastic deformation.

Structural and functional properties of the Kunitz-type and C-terminal domains of Amblyomin-X supporting its antitumor activity.

Amblyomin-X is a Kunitz-type FXa inhibitor identified through the transcriptome analysis of the salivary gland from Amblyomma sculptum tick. This protein consists of two domains of equivalent size, triggers apoptosis in different tumor cell lines, and promotes regression of tumor growth, and reduction of metastasis. To study the structural properties and functional roles of the N-terminal (N-ter) and C-terminal (C-ter) domains of Amblyomin-X, we synthesized them by solid-phase peptide synthesis, solved the X-Ray crystallographic structure of the N-ter domain, confirming its Kunitz-type signature, and studied their biological properties. We show here that the C-ter domain is responsible for the uptake of Amblyomin-X by tumor cells and highlight the ability of this domain to deliver intracellular cargo by the strong enhancement of the intracellular detection of molecules with low cellular-uptake efficiency (p15) after their coupling with the C-ter domain. In contrast, the N-ter Kunitz domain of Amblyomin-X is not capable of crossing through the cell membrane but is associated with tumor cell cytotoxicity when it is microinjected into the cells or fused to TAT cell-penetrating peptide. Additionally, we identify the minimum length C-terminal domain named F2C able to enter in the SK-MEL-28 cells and induces dynein chains gene expression modulation, a molecular motor that plays a role in the uptake and intracellular trafficking of Amblyomin-X.