Structures of DPAGT1 Explain Glycosylation Disease Mechanisms and Advance TB Antibiotic Design.

Protein N-glycosylation is a widespread post-translational modification. The first committed step in this process is catalysed by dolichyl-phosphate N-acetylglucosamine-phosphotransferase DPAGT1 (GPT/E.C. 2.7.8.15). Missense DPAGT1 variants cause congenital myasthenic syndrome and disorders of glycosylation. In addition, naturally-occurring bactericidal nucleoside analogues such as tunicamycin are toxic to eukaryotes due to DPAGT1 inhibition, preventing their clinical use. Our structures of DPAGT1 with the substrate UDP-GlcNAc and tunicamycin reveal substrate binding modes, suggest a mechanism of catalysis, provide an understanding of how mutations modulate activity (thus causing disease) and allow design of non-toxic "lipid-altered" tunicamycins. The structure-tuned activity of these analogues against several bacterial targets allowed the design of potent antibiotics for Mycobacterium tuberculosis, enabling treatment in vitro, in cellulo and in vivo, providing a promising new class of antimicrobial drug.

Agreement Between Maximal Lactate Steady State and Critical Power in Different Sports: A Systematic Review and Bayesian's Meta-Regression.

ABSTRACT: Borszcz, FK, de Aguiar, RA, Costa, VP, Denadai, BS, and de Lucas, RD. Agreement between maximal lactate steady state and critical power in different sports: A systematic review and Bayesian's meta-regression. J Strength Cond Res 38(6): e320-e339, 2024-This study aimed to systematically review the literature and perform a meta-regression to determine the level of agreement between maximal lactate steady state (MLSS) and critical power (CP). Considered eligible to include were peer-reviewed and "gray literature" studies in English, Spanish, and Portuguese languages in cyclical exercises. The last search was made on March 24, 2022, on PubMed, ScienceDirect, SciELO, and Google Scholar. The study's quality was evaluated using 4 criteria adapted from the COSMIN tool. The level of agreement was examined by 2 separate meta-regressions modeled under Bayesian's methods, the first for the mean differences and the second for the SD of differences. The searches yielded 455 studies, of which 36 studies were included. Quality scale revealed detailed methods and small samples used and that some studies lacked inclusion/exclusion criteria reporting. For MLSS and CP comparison, likely (i.e., coefficients with high probabilities) covariates that change the mean difference were the MLSS time frame and delta criteria of blood lactate concentration, MLSS number and duration of pauses, CP longest predictive trial duration, CP type of predictive trials, CP model fitting parameters, and exercise modality. Covariates for SD of the differences were the subject's maximal oxygen uptake, CP's longest predictive trial duration, and exercise modality. Traditional MLSS protocol and CP from 2- to 15-minute trials do not reflect equivalent exercise intensity levels; the proximity between MLSS and CP measures can differ depending on test design, and both MLSS and CP have inherent limitations. Therefore, comparisons between them should always consider these aspects.

Comparison of NIRS exercise intensity thresholds with maximal lactate steady state, critical power and rowing performance.

This study aimed to compare the intensity of deoxygenated haemoglobin concentration ([HHb]) and tissue saturation index (TSI) breakpoints ([HHb]-BP and TSI-BP) with maximal lactate steady state (MLSS) and critical power (CP), and to describe their association with 2000-m rowing ergometer performance. Fourteen male rowers performed on a rowing ergometer: I) a discontinuous incremental test with 3-min stages (INC3); II) a continuous incremental test with 1-min stages (INC1); III) constant workload tests to determine MLSS; and IV) performance tests of 500 m, 1000 m, 2000 m and 6000 m to determine CP.CP (257 ± 39 W; 3.79 ± 4.1 L · min-1) was higher than [HHb]-BP3 (205 ± 26 W; 3.48 ± 2.9 L · min-1), [HHb]-BP1 (207 ± 27 W; 3.27 ± 3.2 L · min-1), and TSI-BP3 (218 ± 31 W; 3.51 ± 3.0 L · min-1), but not higher than TSI-BP1 (222 ± 34 W; 3.43 ± 3.2 L · min-1). MLSS (187 ± 26 W; 3.33 ± 3.2 L · min-1) was lower than TSI-BP3 and TSI-BP1 for power output, but not different in any comparison for ⩒O2. The limits of agreement for power output and ⩒O2 suggest poor agreement among these thresholds. The low level of agreement compromises the use of [HHb]-BP and TSI-BP for estimating MLSS and CP; therefore, these thresholds should not be considered interchangeable.

Ketogenic diets, exercise performance, and training adaptations.

PURPOSE OF REVIEW: The ketogenic diet has been proposed as a nutritional strategy in sports. This review was undertaken to provide an overview of the recent literature concerning the effects of ketogenic diet on exercise performance and training adaptations. RECENT FINDINGS: Most recent literature on the ketogenic diet and exercise performance showed no beneficial effects, especially for trained individuals. During a period of intensified training, performance was clearly impaired during the ketogenic intervention, while a diet with high carbohydrates maintained physical performance. The main effect of the ketogenic diet resides in metabolic flexibility, inducing the metabolism to oxidize more fat for ATP resynthesis regardless of submaximal exercise intensities. SUMMARY: The ketogenic diet is not a reasonable nutritional strategy, as it has no advantage over normal/high carbohydrate-based diets on physical performance and training adaptations even when used only in a specific training/nutritional periodization stage.

Effects of the ketogenic diet on performance and body composition in athletes and trained adults: a systematic review and Bayesian multivariate multilevel meta-analysis and meta-regression.

This systematic review with meta-analysis aimed to determine the effects of the ketogenic diet (KD) against carbohydrate (CHO)-rich diets on physical performance and body composition in trained individuals. The MEDLINE, EMBASE, CINAHL, SPORTDiscus, and The Cochrane Library were searched. Randomized and non-randomized controlled trials in athletes/trained adults were included. Meta-analytic models were carried out using Bayesian multilevel models. Eighteen studies were included providing estimates on cyclic exercise modes and strength one-maximum repetition (1-RM) performances and for total, fat, and free-fat masses. There were more favorable effects for CHO-rich than KD on time-trial performance (mode [95% credible interval]; -3.3% [-8.5%, 1.7%]), 1-RM (-5.7% [-14.9%, 2.6%]), and free-fat mass (-0.8 [-3.4, 1.9] kg); effects were more favorable to KD on total (-2.4 [-6.2, 1.8] kg) and fat mass losses (-2.4 [-5.4, 0.2] kg). Likely modifying effects on cyclic performance were the subject's sex and VO2max, intervention and performance durations, and mode of exercise. The intervention duration and subjects' sex were likely to modify effects on total body mass. KD can be a useful strategy for total and fat body losses, but a small negative effect on free-fat mass was observed. KD was not suitable for enhancing strength 1-RM or high-intensity cyclic performances.

Synthesis and antimicrobial activity of aminoalkyl resveratrol derivatives inspired by cationic peptides.

Antimicrobial resistance is a global concern, far from being resolved. The need of new drugs against new targets is imminent. In this work, we present a family of aminoalkyl resveratrol derivatives with antibacterial activity inspired by the properties of cationic amphipathic antimicrobial peptides. Surprisingly, the newly designed molecules display modest activity against aerobically growing bacteria but show surprisingly good antimicrobial activity against anaerobic bacteria (Gram-negative and Gram-positive) suggesting specificity towards this bacterial group. Preliminary studies into the action mechanism suggest that activity takes place at the membrane level, while no cross-resistance with traditional antibiotics is observed. Actually, some good synergistic relations with existing antibiotics were found against Gram-negative pathogens. However, some cytotoxicity was observed, despite their low haemolytic activity. Our results show the importance of the balance between positively charged moieties and hydrophobicity to improve antimicrobial activity, setting the stage for the design of new drugs based on these molecules.

Association between internal training load and muscle injuries in Brazilian professional soccer players.

The training load is associated with injury risk in a variety of sports. This study aimed to evaluate the association between the internal training load and injury risk in Brazilian professional soccer players. The data were collected from 32 soccer players across two full seasons (2017 and 2018). The rating of perceived exertion (RPE) for every training/match session was used as an internal load variable. The cumulative training load from 3 and 4 weeks (C3 and C4) and the acute:chronic workload ratio (ACWR) were calculated. A generalized estimating equation analysis was applied to examine associations of non-contact muscle injuries with C3, C4 and ACWR. A total of 33 injuries were recorded across the two full seasons. A significant association was found between cumulative training load for three (C3, p = 0.003) and four weeks (C4, p = 0.023) and the occurrence of injuries. Players in the "high load" group presented greater injury risk in relation to the "moderate load" group (C4: OR = 4.5; IC 95% 1.5-13.3; C3: OR = 3.7; IC 95% 1.7-8.1). There was no association between ACWR and injury occurrence. The athletes exposed to a high cumulative load in a period of 3 to 4 weeks presented higher injury risk in comparison to those who had moderate cumulative training loads. Besides that, there was no association between ACWR and injury occurrence.

Chemically Tuning Resveratrol for the Effective Killing of Gram-Positive Pathogens.

In the era of antimicrobial resistance, the identification of new compounds with strong antimicrobial activity and the development of alternative therapies to fight drug-resistant bacteria are urgently needed. Here, we have used resveratrol, a safe and well-known plant-derived stilbene with poor antimicrobial properties, as a scaffold to design several new families of antimicrobials by adding different chemical entities at specific positions. We have characterized the mode of action of the most active compounds prepared and have examined their synergistic antibacterial activity in combination with traditional antibiotics. Some alkyl- and silyl-resveratrol derivatives show bactericidal activity against Gram-positive bacteria in the same low micromolar range of traditional antibiotics, with an original mechanism of action that combines membrane permeability activity with ionophore-related activities. No cross-resistance or antagonistic effect was observed with traditional antibiotics. Synergism was observed for some specific general-use antibiotics, such as aminoglycosides and cationic antimicrobial peptide antibiotics. No hemolytic activity was observed at the active concentrations or above, although some low toxicity against an MRC-5 cell line was noted.

Jiu-Jitsu-Specific Performance Test: Reliability Analysis and Construct Validity in Competitive Athletes.

ABSTRACT: da Silva Junior, JN, Kons, RL, de Lucas, RD, and Detanico, D. Jiu-jitsu-specific performance test: Reliability analysis and construct validity in competitive athletes. J Strength Cond Res 36(1): 174-179, 2022-The aim of this study was twofold: to analyze the test-retest reliability and sensitivity of Jiu-Jitsu "anaerobic" performance test (JJAPT) variables, and to determine the construct validity of JJAPT by comparing groups of athletes with different levels and technical profiles. Sixty Brazilian Jiu-Jitsu (BJJ) athletes participated in this study. The reliability analysis was performed with all athletes and the construct validity was tested in the group comparisons-novice vs. advanced level and guard versus pass fighters. From the JJAPT, the number of repetitions, rate of perceived exertion (RPE) and average heart rate were assessed over the 5 sets. The test-retest reliability was assessed by absolute and relative analysis for each variable. The construct validity was tested by comparison means and the receiving operator characteristic (ROC) curve was used with the level of significance set at 5%. The main results demonstrated excellent test-retest reliability for all but the RPE in the first sets, with good sensitivity and agreement. The maximal number of repetitions in the JJAPT showed good construct validity, as it showed sensitivity to discriminate the performance between the advanced and novice BJJ athletes (p < 0.001, ROC curve area of 0.95). However, no significant difference was found between the technical profile groups (p > 0.05). We concluded that the JJAPT presents excellent performance reliability as a specific-sport test. In addition, the test presented evidence of construct validity, because it discriminated the performance between the advanced and novice BJJ athletes.

What Do We Know about Frame Running? A Narrative Review.

ABSTRACT: This narrative review aims to provide a general overview of the literature about frame running, which is a recent modality of Para-Athletics. Frame running is practiced by using a tricycle without pedals called PETRA RaceRunner, by people with moderate to severe cerebral palsy and other lower limb functional limitations. Briefly, the movement pattern is very similar to walking and running. This review includes studies from scientific databases and content of official sports web sites by using the keywords "framerunning," "racerunning," and "petra racerunning." According to our search, this narrative review highlighted three themes involving the practice of frame running, namely health and quality of life, sports classification, and training and testing in the frame running context.

Determination of the speed-time relationship during handcycling in spinal cord injured athletes.

This study aimed to determine the critical speed (CS) and the work above CS (D') from three mathematical models of para-athletes during a treadmill handcycling exercise. Nine hand-cyclists with spinal cord injuries performed a maximal incremental handcycling test and three tests to exhaustion at a constant speed to determine the speed-time relationship. The three tests to exhaustion were performed at intensities between 90% and 105% of peak speed derived from the incremental test. Then, the determination of CS and D' was modelled by linear and hyperbolic models. CS and D' did not present any significant differences among the three mathematical models. Low values in the standard error of estimate for CS were found for the three models (Linear: Distance-time: 1.7 ± 0.5%; Linear: Speed-1/time: 3.0 ± 1.9% and Hyperbolic: 1.2 ± 0.6%). Based on the simplicity to calculate, the CS modelled by linear-distance-time can be a practical method for handcyclist coaches.

A novel treadmill protocol for uphill running assessment: the incline incremental running test (IIRT).

This study aimed to compare the maximal and submaximal aerobic parameters between two incremental running tests, one being horizontal and the other an incline-based test, namely the incline incremental running test (IIRT). Twenty endurance-trained trail runners completed two incremental treadmill tests, until exhaustion. The first test was performed using an incline of 1%, with speed increments. Then, the IIRT was performed with the speed set at 50% of the peak speed obtained during the previous test, and the incline was incremented. Cardiorespiratory measurements and blood lactate concentration ([La]) were assessed. The mean peak workload from the horizontal test was 17.6 ± 1.4 km.h-1 and peak workload from IIRT was 17.3 ± 1.3% of incline. The VO2peak and [La]peak were not significantly different between the protocols. However, the HRpeak was significantly lower at IIRT. In conclusion, most of the maximal and submaximal aerobic indices showed no differences between the incremental tests analysed. The exceptions were the HRpeak and HR at the lactate turnpoints, that were lower, and the peak O2 pulse that was greater for the IIRT. Taken together, these data support the validity of the IIRT as a specific test for the physiological assessment of runners involved with uphill performances.

Game Running Performance and Fitness in Women's Futsal.

The study aimed to verify possible associations between game-play running performance and outcomes derived from fitness (running) tests in female futsal players. Sixteen women professional elite futsal players from a 1st division league team (19.2±2 years-old, 4.3±2.1 years of experience) participated. Firstly, a graded incremental treadmill test was adopted to determine maximal oxygen uptake (VO2max). Following 72 h of laboratory protocol, players were asked to perform a repeated-sprint test on a court (8×40 m with two 180° change-of-directions). Twenty-four hours after, players participated in a one-off friendly game (two 20-min half-times). A computerized automatic image recognition software (DVIDEOW; 30 Hz) allowed to determine game running performance variables. Fatigue index and best time in the court test and VO2max and its attached speed derived from laboratory-based test showed significant moderate-to-moderately high correlations (r=- 0.59-0.76; p<0.05) with some game running performance outputs, notably related to high-intensity running. In conclusion, the present study provided initial evidence on associations between two fitness tests and one-off game running performance in female futsal. Information derived from the work potentially help conditioning professionals working with female futsal athletes gain awareness about some properties of common testing tools.

Predicting Maximal Lactate Steady State from Carminatti's Shuttle Run Test in Soccer Players.

The objective of the present study was to determine the validity of Carminatti's shuttle run incremental test-T-Car derived parameters in estimating the maximal lactate steady state determined in shuttle run format. Eighteen soccer players performed a T-Car test, and several trials to determine the maximal lactate steady state. From T-Car were derived the heart rate deflection point, peak speed, maximal heart rate and parameters resulting from percentage of peak measures. The validity was accessed by Bland-Altman plots, linear regressions, and two one-sided tests of equivalence analysis. The results showed the speed at 80.4% of T-Car peak speed, the heart rate deflection point and the 91.4% of maximal heart rate were equivalent to maximal lactate steady state (Mean difference; ±90% compatibility interval; -0.8; ±1.5%, -0.4; ±1.1%, and 0.0; ±2.7%, respectively). Additionally, peak speed during the T-Car test was a stronger predictor of maximal lactate steady state (MLSS [km/h]=2.57+0.65 × sPeak; r=0.82 [90% CI; 0.62-0.92], standard error of the estimate=3.6%; 90% CI ×/÷1.4). Therefore, soccer players can use the T-Car derived parameters as a noninvasive and practical alternative to estimate the specific maximal lactate steady state for soccer.

Effects of Caffeine Chewing Gum on Exercise Tolerance and Neuromuscular Responses in Well-Trained Runners.

ABSTRACT: Dittrich, N, Serpa, MC, Lemos, EC, De Lucas, RD, and Guglielmo, LGA. Effects of caffeine chewing gum on exercise tolerance and neuromuscular responses in well-trained runners. J Strength Cond Res 35(6): 1671-1676, 2021-This study aimed to investigate the effects of caffeinated chewing gum on endurance exercise, neuromuscular properties, and rate of perceived exertion on exercise tolerance. Twelve trained male runners (31.3 ± 6.4 years; 70.5 ± 6.6 kg; 175.2 ± 6.2 cm; 9.4 ± 2.7% body fat; and V̇o2max = 62.0 ± 4.2 ml·kg-1·min-1) took part of the study. The athletes performed an intermittent treadmill test to determine maximal aerobic speed and delta 50% (Δ50%) intensity. In the following visits, they performed 2 randomized time to exhaustion tests (15.4 ± 0.7 km·h-1) after the ingestion of 300 mg of caffeine in a double-blind, crossover, randomized design. Maximal voluntary contraction of the knee extensor associated to surface electromyographic recording and the twitch interpolation technique were assessed before and immediately after the tests to quantify neuromuscular fatigue of the knee extensor muscles. Caffeine significantly improved exercise tolerance by 18% (p < 0.01). Neuromuscular responses decreased similarly after time to exhaustion in both exercise conditions; however, athletes were able to run a longer distance in the caffeine condition. The performance improvement induced by caffeine seems to have a neuromuscular contribution because athletes were able to run a longer distance with the same neuromuscular impairment.

The Resveratrol Prodrug JC19 Delays Retinal Degeneration in rd10 Mice.

It has been reported that resveratrol (RES) has a therapeutic effect in different neurodegenerative and ocular diseases. However, RES is rapidly eliminated from the organism, and high doses need to be administered resulting in potential toxic side effects. We hypothesized that a RES prodrug such as 3,4'-diglucosyl resveratrol (JC19) would reduce RES metabolism to produce a neuroprotective effect. Here, we have examined the protective effect of JC19 in an experimental mouse model of autosomal recessive RP. Rd10 mice at postnatal day 13 (P13) were subretinally injected with vehicle and two different doses of JC19. Electroretinogram (ERG) and histological evaluation were performed 15 days after injections. The amplitude of a- and b-waves was quantified in ERG recordings, and the number of photoreceptor nuclei in the outer nuclear layer was counted. In addition, the mouse retinas were immunostained with anti-rhodopsin antibodies. JC19 treatment delayed the loss of rod photoreceptor in rd10 mice, maintaining the expression of rhodopsin and preserving their electrical responses to light stimuli. The exact mechanism by which RES delays retinal degeneration in rd10 mice remains to be elucidated, but Sirtuin 1 activation could be one of the key molecular pathways involved in its neuroprotective effect.

Nanostructured Chitosan-Based Biomaterials for Sustained and Colon-Specific Resveratrol Release.

In the present work, we demonstrate the preparation of chitosan-based composites as vehicles of the natural occurring multi-drug resveratrol (RES). Such systems are endowed with potential therapeutic effects on inflammatory bowel diseases (IBD), such as Crohn's disease (CD) and ulcerative colitis, through the sustained colonic release of RES from long-lasting mucoadhesive drug depots. The loading of RES into nanoparticles (NPs) was optimized regarding two independent variables: RES/polymer ratio, and temperature. Twenty experiments were carried out and a Box⁻Behnken experimental design was used to evaluate the significance of these independent variables related to encapsulation efficiency (EE). The enhanced RES EE values were achieved in 24 h at 39 °C and at RES/polymer ratio of 0.75:1 w/w. Sizes and polydispersities of the optimized NPs were studied by dynamic light scattering (DLS). Chitosan (CTS) dispersions containing the RES-loaded NPs were ionically gelled with tricarballylic acid to yield CTS-NPs composites. Macro- and microscopic features (morphology and porosity studied by SEM and spreadability), thermal stability (studied by TGA), and release kinetics of the RES-loaded CTS-NPs were investigated. Release patterns in simulated colon conditions for 48 h displayed significant differences between the NPs (final cumulative drug release: 79⁻81%), and the CTS-NPs composites (29⁻34%).

Comparative Effects of Two Interval Shuttle-Run Training Modes on Physiological and Performance Adaptations in Female Professional Futsal Players.

Teixeira, AS, Arins, FB, De Lucas, RD, Carminatti, LJ, Dittrich, N, Nakamura, FY, and Guglielmo, LGA. Comparative effects of two interval shuttle-run training modes on physiological and performance adaptations in female professional futsal players. J Strength Cond Res 33(5): 1416-1428, 2019-The purpose of this study was to analyze the effects of 2 shuttle-run interval training (SRIT) models with 1 and 3 directional changes per running bout on the aerobic and anaerobic performances of elite female futsal players. Sixteen players competing in the Brazilian National Division League took part in the study. The training protocols consisted of shuttle-run intervals organized in 4 sets of 4-minute bouts with 3 minutes of rest intervals between the sets. The SRIT models were composed of 1 (7.5 seconds running and 7.5 seconds pause [SRIT7.5×7.5]; n = 7) or 3 (15 seconds running and 15 seconds pause [SRIT15×15]; n = 9) directional changes. The athletes performed the following tests before and after a 5-week training period: incremental treadmill test (ITT), futsal intermittent endurance test (FIET) (with respective peak speeds [PSs]), and a repeated sprint ability (RSA) test. After the training period, PSFIET and speed at the second lactate turnpoint were very likely and almost certainly increased in both training regimens, respectively. SRIT15×15 induced possibly greater improvements in PSITT (+3.28%, 90% CL -0.16 to 6.82) and RSAmean (+1.17%, 90% CL -0.68 to 3.05) than SRIT7.5×7.5. In addition, SRIT15×15 resulted in a likely greater improvement in running economy (+4.33%, 90% CL -0.35 to 9.23) compared with SRIT7.5×7.5. In elite female futsal players, SRIT15×15 is a promising strategy to enhance performance-related physical fitness attributes in a short-term period (5 weeks) during the preseason, Because of its superior effects on these important aerobic and anaerobic qualities than a protocol with fewer directional changes.

Objectively measured daily-life physical activity of moderate-to-severe Brazilian asthmatic women in comparison to healthy controls: A cross-sectional study.

Considering the complex relationship between asthma symptoms and exercise, asthmatics are usually believed to be less active in daily life than healthy subjects. However, few studies have objectively assessed daily-life physical activity (DLPA) of asthmatic adults. OBJECTIVE: To objectively assess DLPA of a sample of Brazilian asthmatic women in comparison to healthy controls, and to investigate the associations between DLPA and asthma control, health-related quality of life, anxiety and depression levels, and the Six-minute walk test (6MWT) in this population. METHODS: Sixty-six women were included, 36 in the asthma group (AG) and 30 in the control group (CG). The AG was composed by clinically stable moderate-to-severe asthmatics. The CG was composed by apparently healthy volunteers. All subjects underwent DLPA assessment (considered as the average of steps taken during six consecutive days measured by a pedometer) and performed the 6MWT. Additionally, participants in the AG were assessed using the Asthma Control Questionnaire, the Asthma Quality of Life Questionnaire (AQLQ), and the Hospital Anxiety and Depression Scale. RESULTS: There was no difference between the AG and the CG regarding DLPA (7490.3 ± 3330.2 vs 6876.4 ± 3242.1 steps respectively, p = 0.45), even after adjustment for covariates. DLPA was significantly correlated to the activity limitation domain of the AQLQ among asthmatics (r = 0.43, p < 0.01). CONCLUSION: Despite the association between self-perceived activity limitation and DLPA among asthmatics, there were no differences regarding DLPA between a sample of moderate-to-severe Brazilian asthmatic women and apparently healthy controls.

Synthesis, Binding Properties, and Differences in Cell Uptake of†G-Quadruplex Ligands Based on Carbohydrate Naphthalene Diimide Conjugates.

The G-quadruplexes (G4s) are currently being explored as therapeutic targets in cancer and other pathologies. Six carbohydrate naphthalene diimide conjugates (carb-NDIs) have been synthesized as G4 ligands to investigate their potential selectivity in G4 binding and cell penetration. Carb-NDIs have shown certain selectivity for G4 structures against DNA duplexes, but different sugar moieties do not induce a preference for a specific G4 topology. Interestingly, when monosaccharides were attached through a short ethylene linker to the NDI scaffold, their cellular uptake was two- to threefold more efficient than that when the sugar was directly attached through its anomeric position. Moreover, a correlation between more efficient cell uptake of these carb-NDIs and their higher toxicity in cancerous cell lines has been observed. Carb-NDIs seem to be mainly translocated into cancer cells through glucose transporters (GLUT), of which GLUT4 plays a major role.