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The interest in the antineoplastic and binding properties shown by the bis-maltol polyamine family, particularly Malten and Maltonis, prompted us to study the Pd 2+ complexes of these latter from both a biological and metallo-receptor point of view. The Malten-Pd 2+ complex can lodge hard species such as Sr 2+ in its coordination-driven preorganized pocket, as confirmed by X-ray diffraction. UV-Vis and NMR data showed that Malten-Pd 2+ forms even at acidic pH and exists in aqueous solution in a wide range of pH. The mononuclear complex is stable enough not to release Pd 2+ in solution for a long period of time (at least one week), thus Malten-Pd 2+ , similarly to Maltonis-Pd 2+ , is suitable to be tested in biological analyses. Studies on the U937 cell line revealed that the effect on cell survival reduction induced by Malten is partially lost in Malten-Pd 2+ , while no differences where monitored between the effects of Maltonis-Pd 2+ and Maltonis, suggesting that the availability of free maltol moieties, that is retained in Maltonis-Pd 2+ , but not in Malten-Pd 2+ , is crucial to guarantee the biological activity of these compounds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The main purpose of this longitudinal study was to investigate football players' recovery status, through hormonal response, in relation to accumulated workload at two comparable time points of the first (T1) and second half (T2) of the competitive season. Moreover, this study investigated athletes' hormonal response to a typical weekly conditioning session (5 days before match: MD-5), at T1 and T2, to detect changes in players' recovery capability over time. Salivary cortisol (sC) and testosterone (sT) of 24 professional players (27.8 ± 4.1 years of age) were collected before, after, and 24 hours following MD-5 in two comparable microcycles of T1 and T2. GPS training data (total and high-intensity distance) of the 7 and 28 days before sampling were used to obtain athletes' acute and chronic workloads. Results showed a pre-training significant decrease of sT and an increase of sC (p<0.05) in T2, compared to T1. Moreover, athletes showed high sC and low sT levels before, after and 24 hours following MD-5 in T2. Workload analysis revealed significant correlations of chronic load with sC (r = 0.45, p = 0.056) and T/C ratio (r = -0.59; p = 0.007). These results suggested that, in professional football, chronic workload has a greater impact on players' recovery time than acute workload over the sport season. Moreover, athletes' hormonal response to the weekly conditioning session at T2 revealed an altered anabolic/catabolic balance, highlighting the key role of continuous internal and external workload monitoring during the season., Competing Interests: The authors report there are no competing interests to declare., (Copyright: © 2024 Curzi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This paper examined the relationship among countermovement jump (CMJ), football category, chronological age, relative age, and pubertal development status to investigate which parameter could be better associated with jumping performance. We tested 259 young male football players (14.9 ± 1.8 yrs; 169.7 ± 9.8 cm; 60.6 ± 11.3 kg; 20.9 ± 2.6 kg m -2 ) belonging to elite football academies. One-sample chi-square tests were used to test the uniformity of distributions of the proportions of players in each year quarter (relative age effect, RAE) for the whole sample and stratified for each football age category (U14, U15, U17, and U19). One-way ANOVAs were used to test the associations among a) categories, RAE, and CMJ, and b) the pubertal status category and CMJ. Pearson's correlation assessed the relationship among variables. The birth distribution among the year's quarters significantly differed from the expected proportion of 25 % of participants each quarter ( χ 2  = 41.74; p  < 0.001), highlighting the presence of a relative age effect. Results indicate that age significantly influences CMJ ( F (6,231)  = 8.85, p  < 0.001, η 2 p  = 0.187), and a significant interaction effect (age × birth quarter) was found. Coaches, strength and conditioning trainers, and scouts should be aware of physical and biological players' maturation., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Abstract: Amatori, S, Helsen, WF, Baldari, C, Serra, T, Belli, A, Guidetti, L, Rocchi, MBL, Sisti, D, and Perroni, F. High-speed efforts of elite association football referees in national and international matches. J Strength Cond Res 38(8): e417-e422, 2024-Field referees (FRs) need to move throughout the pitch to identify any infringements of the game's laws. Their performance depends on technical, tactical, physical, physiological, and mental factors. This retrospective study aimed to examine and assess the physical and physiological parameters as a function of time in elite association football referees during official matches. Global positioning system (match time, distance in different intensity ranges [low-intensity, high-speed, very high-speed running, and sprinting], average and peak speed, distance in accelerations or decelerations) and heart rate (average and peak) data from 212 national and international football matches were analyzed. A linear mixed-model analysis was performed to assess the differences between halves and between the three 15-minute sections of each half-time for all the physical and physiological variables collected. A significant effect of match half was found for the game time (p < 0.001) and the standing time (p = 0.005), both higher in the second half, and for the average speed (p = 0.017), which was lower in the second half. Total distance (p < 0.001), low-intensity distance (p = 0.004), and average speed (p = 0.007) all showed a reduction as a function of time. More than 7.800 high-speed intervals were detected. Accelerative actions within 3 seconds characterized most of the high-speed efforts of an FR during a match. Significant differences emerged in the way the match intensity is distributed across the match, analyzed both in halves (first vs. second) and 15-minute intervals within each half. It is important to emphasize the importance of high-speed training with a focus on a faster transition from low- to high-speed running to keep up with the play to get into an appropriate position and subsequently make the correct decisions., (Copyright © 2024 National Strength and Conditioning Association.)

In the framework of the design, synthesis and testing of a library of copper complexes and nanostructured assemblies potentially endowed with antitumor and antiviral activity and useful for several applications, from drugs and related delivery systems to the development of biocidal nanomaterials, we present the detailed spectroscopic investigation of the molecular and electronic structure of copper-based coordination compounds and of a new conjugated system obtained by grafting Cu(I) complexes to gold nanorods. More in detail, the electronic and molecular structures of two Cu complexes and one AuNRs/Cu-complex adduct were investigated by X-ray photoelectron spectroscopy (XPS), synchrotron-induced XPS (SR-XPS) and near edge X-ray absorption spectroscopy (NEXAFS) in solid state, and the local structure around copper ion was assessed by X-ray absorption spectroscopy (XAS) both in solid state and water solution for the AuNRs/Cu-complex nanoparticles. The proposed multi-technique approach allowed to properly define the coordination geometry around the copper ion, as well as to ascertain the molecular structures of the coordination compounds, their stability and modifications upon interaction with gold nanoparticles, by comparing solid state and liquid phase data., (© 2024 Wiley-VCH GmbH.)

The new ligand L 2Ad , obtained by conjugating the bifunctional species bis(3,5-dimethylpyrazol-1-yl)-acetate and the drug amantadine, was used as a chelator for the synthesis of new Cu complexes 1 - 5 . Their structures were investigated by synchrotron radiation-induced X-ray photoelectron spectroscopy (SR-XPS), near-edge X-ray absorption fine structure (NEXAFS) spectroscopy, and by combining X-ray absorption fine structure (XAFS) spectroscopy techniques and DFT modeling. The structure of complex 3 was determined by single-crystal X-ray diffraction analysis. Tested on U87, T98, and U251 glioma cells, Cu(II) complex 3 and Cu(I) complex 5 decreased cell viability with IC 50 values significantly lower than cisplatin, affecting cell growth, proliferation, and death. Their effects were prevented by treatment with the Cu chelator tetrathiomolybdate, suggesting the involvement of copper in their cytotoxic activity. Both complexes were able to increase ROS production, leading to DNA damage and death. Interestingly, nontoxic doses of 3 or 5 enhanced the chemosensitivity to Temozolomide.

The influence of biological maturity status on talent identification and development in youth soccer has been debated extensively. Alternative methods have thus recently emerged to estimate maturity status, such as the Pubertal Development Scale (PDS), but their relationship with physical capabilities of young soccer players still needs to be determined. The present study investigated the relationships of different PDS-derived pubertal status measures, chronological age, and relative age with selected performance variables in youth soccer. Sixty-one male soccer players were assessed for physical capabilities using field tests for sprinting, vertical jumps (countermovement jump, CMJ), intermittent high-intensity endurance, and repeated sprint ability. Chronological age was defined as the number of days since birth, and relative age was defined in terms of age quarters. PDS-derived measures of puberal status, otherwise, were determined as an average PDS score, a PDS category score, and a pubertal category. Chronological age, relative age, and measures of pubertal status were scarcely related (p > 0.05) to selected measures of soccer performance. Significant correlations were only found between different measures of pubertal status and the variable "work" in the CMJ test (range r = 0.33-0.36; p < 0.01) and between chronological age and CMJ height (r = -0.297; p = 0.02). The present results suggest that physical performance of young soccer players is poorly related to chronological age, relative age, and pubertal status. Potential effects of biological maturity status on physical capabilities may not be easily identifiable in a group of young soccer players narrowed in terms of chronological age and training status., Competing Interests: The authors declare no conflict of interest., (Copyright: © Academy of Physical Education in Katowice.)

Introduction: Both mental and physical health of office workers had a positive relationship with their work engagement, with the latter relationship being driven by the association of a healthy diet and physical activity (PA). This observational study aimed to investigate the associations between PA levels, musculoskeletal disorders (MSDs), burnout, and work engagement, in a sample of white-collar employees., Methods: A total of 615 workers (age 42.2 ± 9.5 years) successfully completed an online questionnaire comprising work-related information and standardized questionnaires on PA, MSDs, burnout and work engagement., Results: 36.9% of the participants did not meet the PA guidelines, 19.0% adhered to them, and 44.1% exceeded them. A significant portion of participants reported suffering from MSDs, primarily neck/shoulder and/or low back/hip pain. Those exceeding PA guidelines had fewer MSDs compared to non-compliant participants and exhibited better mental health and work engagement. Compliance with PA guidelines was associated with a 38% reduced risk of emotional exhaustion, with an even greater reduction of 47% among those surpassing the guidelines., Discussion: PA could exert a positive effect on physical and mental health of employees, but only if performed above a certain amount. The study supports the need to identify workplaces as suitable for health-focused interventions and lifestyle changes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Amatori, Gobbi, Sisti, Pivato, Giombini, Rombaldoni, Calcagnini, Rocchi and Perroni.)

The histone deacetylase sirtuin 6 (SIRT6) has been endowed with anti-cancer capabilities in many tumor types. Here, we investigate the impact of SIRT6-overexpression (SIRT6-OE) in Delta16HER2 mice, which are a bona fide model of HER2-positive breast cancer. After an initial delay in the tumor onset, SIRT6-OE induces a more aggressive phenotype of Delta16HER2 tumors promoting the formation of higher number of tumor foci and metastases than controls. This phenotype of SIRT6-OE tumors is associated with cancer stem cell (CSC)-like features and tumor dormancy, and low senescence and oxidative DNA damage. Accordingly, a sub-set of HER2-positive breast cancer patients with concurrent SIRT6-OE has a significant poorer relapse-free survival (RFS) probability than patients with low expression of SIRT6. ChIP-seq, RNA-seq and RT-PCR experiments indicate that SIRT6-OE represses the expression of the T-box transcription factor 3 (Tbx3) by deacetylation of H3K9ac. Accordingly, loss-of-function mutations of TBX3 or low TBX3 expression levels are predictive of poor prognosis in HER2-positive breast cancer patients. Our work indicates that high levels of SIRT6 are indicative of poor prognosis and high risk of metastasis in HER2-positive breast cancer and suggests further investigation of TBX3 as a downstream target of SIRT6 and co-marker of poor-prognosis. Our results point to a breast cancer subtype-specific effect of SIRT6 and warrant future studies dissecting the mechanisms of SIRT6 regulation in different breast cancer subtypes., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: In haemodialysis is key to successfully obtaining cannulation of the arteriovenous fistula (AVF). The literature agrees that cannulation, failing in the initial maturation period, can lead to delayed dialysis, haematoma, scarring, needle phobia and loss of confidence in the cannulator. The introduction of plastic cannulae for haemodialysis has changed cannulation practice positively, preventing frequent complications such as infiltration or trauma. Despite that, most countries have continued to use metal cannulation, in particular in Europe. This study investigates the common use of plastic cannulae versus metal needles for cannulation in dialysis units and explores the implications of focusing on the side effects of cannulation., Methods: The study is a cross-sectional survey. A questionnaire was created by a team of experts from the European Dialysis Transplant Nurse Association/European Renal Care Association (EDTNA/ERCA) to address the study's aims and sent online to nurse members., Results: Data collected suggested a strong resistance towards using plastic cannulae, with few respondents claiming to use these cannulas. Most of the respondents were female (74%), Europeans, working in nephrology for more than 10 years and most worked in the public sector. There was a strong correlation between the use of plastic cannulae and fewer adverse events in elbow located AVF and newly created or fragile AVF., Conclusions: The results are in line with the current literature. Possible resistance to the use of the plastic device includes the difference in cost between the two devices in favour of metal needles. However, it should be considered that the lower number of adverse events, in particular infiltration and haematoma caused by the metal needle, involves a considerable saving both in money and in terms of time and distress for the patient., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Breast cancer (BC) is the second-leading cause of cancer-related death worldwide. This study aimed to investigate the effects of a 12-week home-based lifestyle intervention (based on nutrition and exercise) on gut microbial composition in twenty BC survivors of the MoviS clinical trial (protocol: NCT04818359)., Methods: Gut microbiota analysis through 16S rRNA gene sequencing, anthropometrics, Mediterranean Diet (MD) adherence, and cardiometabolic parameters were evaluated before (Pre) and after (Post) the lifestyle intervention (LI)., Results: Beneficial effects of the LI were observed on MD adherence, and cardiometabolic parameters (pre vs post). A robust reduction of Proteobacteria was observed after LI, which is able to reshape the gut microbiota by modulating microorganisms capable of decreasing inflammation and others involved in improving the lipid and glycemic assets of the host. A significant negative correlation between fasting glucose and Clostridia&#95;vadinBB60 (r = -0.62), insulin and homeostatic model assessment (HOMA) index and Butyricicoccus genera (r = -0.72 and -0.66, respectively), and HDL cholesterol and Escherichia/Shigella (r = -0.59) have been reported. Moreover, positive correlations were found between MD adherence and Lachnospiraceae&#95;ND3007 (r = 0.50), Faecalibacterium (r = 0.38) and Butyricimonas (r = 0.39)., Conclusion: These data suggest that adopting a healthy lifestyle, may contribute to ameliorate several biological parameters that could be involved in the prevention of cancer relapses through the modulation of gut microbiota., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that can be construed as a potential conflict of interest., (Copyright © 2023 Donati Zeppa, Natalucci, Agostini, Vallorani, Amatori, Sisti, Rocchi, Pazienza, Perri, Villani, Binda, Panebianco, Mencarelli, Ciuffreda, Ferri Marini, Annibalini, Lucertini, Bartolacci, Imperio, Virgili, Catalano, Piccoli, Stocchi, Emili and Barbieri.)

This study aimed to assess if, during incremental exercise, considering individual characteristics can make the relationship between the percentages of heart rate (HRR) and oxygen uptake ( V̇ O 2 R) reserve either 1:1 or more accurate. Cycle ergometer data of the maximal incremental exercise tests performed by 450 healthy and sedentary participants (17-66 years) of the HERITAGE Family Study, grouped for sex, ethnicity, age, body fat, resting HR, and V̇ O 2max , were used to calculate the individual linear regressions between %HRR and % V̇ O 2 R. The mean slope and intercept of the individual linear regressions of each subgroup were compared with 1 and 0 (identity line), respectively, using Hotelling tests followed by post-hoc one-sample t -tests. Two multiple linear regressions were also performed, using either the slopes or intercepts of the individual linear regressions as dependent variables and sex, age, resting HR, and V̇ O 2max as independent variables. The mean %HRR-% V̇ O 2 R relationships of all subgroups differed from the identity line. Moreover, individual linear regression intercepts (8.9 ± 16.0) and slopes (0.971 ± 0.190) changed ( p  < 0.001) after 20 weeks of aerobic training (13.1 ± 11.1 and 0.891 ± 0.122). The multiple linear regressions could explain only 3.8% and 1.3% of the variance in the intercepts and slopes, whose variability remained high (standard error of estimate of 15.8 and 0.189). In conclusion, the %HRR-% V̇ O 2 R relationship differs from the identity line regardless of individual characteristics and their difference increased after aerobic training. Moreover, due to the high interindividual variability, using a single equation for the whole population seems not suitable for representing the %HRR-% V̇ O 2 R relationship of a given subject, even when several individual characteristics are considered. Highlights The association between %HRR and % V̇ O 2 R is not 1:1 even when individuals are grouped by age, sex, ethnicity, body composition, HR rest , and V̇ O 2max .Using several subject characteristics to identify the individual's %HRR-% V̇ O 2 R relationship does not meaningfully increase its prediction accuracy or reduce the interindividual variability of %HRR-% V̇ O 2 R relationshipsUsing a single equation for the whole population is not suitable for representing the relationship of a given subject; hence, individual relationships should be preferred when prescribing the intensity of aerobic exercise.The individual %HRR-% V̇ O 2 R relationship should be periodically assessed due to the potential training induced changes in the relationship.

Abstract: Perroni, F, Castagna, C, Amatori, S, Gobbi, E, Vetrano, M, Visco, V, Guidetti, L, Baldari, C, Luigi Rocchi, MB, and Sisti, D. Use of exploratory factor analysis to assess the fitness performance of youth football players. J Strength Cond Res 37(7): e430-e437, 2023-Football performance involves several physical abilities that range in aerobic, anaerobic, and neuromuscular domains; however, little is known about their interplay in profiling individual physical attributes. This study aimed to profile physical performance in youth football players according to their training status. One hundred seven young male soccer players (age 13.5 ± 1.4 years; height 168 ± 7 cm; body mass 57.4 ± 9.6 kg; and body mass index 20.2 ± 2.1 kg·m -2 ) volunteered for this study. Players' physical performance was assessed with football-relevant field tests for sprinting (10 m sprint), vertical jump (countermovement jump), intermittent high-intensity endurance (Yo-Yo Intermittent Recovery Test Level 1, YYIRT1), and repeated sprint ability (RSA). The training status was assumed as testosterone and cortisol saliva concentrations; biological maturation was estimated using the Pubertal Development Scale. Exploratory factor analysis (EFA) revealed 3 main variables depicting anthropometric (D1, 24.9%), physical performance (D2, 18.8%), and training status (D3, 13.3%), accounting for 57.0% of total variance altogether. The level of significance was set at p ≤ 0.05. The RSA and YYIRT1 performances were largely associated with D2, suggesting the relevance of endurance in youth football. This study revealed that for youth football players, a 3-component model should be considered to evaluate youth soccer players. The EFA approach may help to disclose interindividual differences useful to talent identification and selection., (Copyright © 2023 National Strength and Conditioning Association.)

Low-energy electrons (Auger electrons) can be produced via the interaction of photons with gold atoms in gold nanorods (AuNRs). These electrons are similar to those emitted during the decay of technetium-99m ( 99m Tc), a radioactive nuclide widely used for diagnostics in nuclear medicine. Auger and internal conversion (IC) electron emitters appropriately targeted to the DNA of tumors cells may, therefore, represent a new radiotherapeutic approach. 99m Tc radiopharmaceuticals, which are used for diagnosis, could indeed be used in theragnostic fields when loaded on AuNRs and delivered to a tumor site. This work aims to provide a proof of concept (i) to evaluate AuNRs as carriers of 99m Tc-based radiopharmaceuticals, and (ii) to evaluate the efficacy of Auger electrons emitted by photon-irradiated AuNRs in inducing radio-induced damage in T98G cells, thus mimicking the effect of Auger electrons emitted during the decay of 99m Tc used in clinical settings. Data are presented on AuNRs' chemical characterization (with an aspect ratio of 3.2 and Surface Plasmon Resonance bands at 520 and 680 nm) and the loading of pharmaceuticals (after 99m Tc decay) on their surface. Spectroscopic characterizations, such as UV-Vis and synchrotron radiation-induced X-ray photoelectron (SR-XPS) spectroscopies, were performed to investigate the drug-AuNR interaction. Finally, preliminary radiobiological data on cell killing with AuNRs are presented.

Gold nanorods stabilized by binary ligand mixtures of cetyltrimethylammonium bromide (CTAB, primary ligand) and ascorbic acid or hydroquinone were investigated by complementary synchrotron radiation-induced spectroscopies and microscopies, with the aim to find evidence of the influence of the secondary ligand molecular and chemical structure on the nanorod shapes and size ratios. Indeed, as it is well known that the CTAB interaction with Ag(i) ions at the NR surface plays a key role in directing the anisotropic growth of nanorods, the possibility to finely control the NR shape and dimension by opportunely selecting the secondary ligands opens new perspectives in the design and synthesis of anisotropic nanoparticles., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Acute promyelocytic leukemia (APL) is an aggressive subtype of acute myeloid leukemia (AML) in which the PML/RARα fusion protein exerts oncogenic activities by recruiting repressive complexes to the promoter of specific target genes. Other epigenetic perturbations, as alterations of histone H3 lysine 9 trimethylation (H3K9me3), have been frequently found in AMLs and are associated with leukemogenesis and leukemia progression. Here, we characterized the epigenomic effects of maltonis, a novel maltol-derived molecule, in APL cells. We demonstrate that maltonis treatments induce a profound remodulation of the histone code, reducing global H3K9me3 signal and modulating other histone post-translational modifications. Transcriptomic and epigenomic analyses revealed that maltonis exposure induces changes of genes expression associated with a genomic redistribution of histone H3 lysine 4 trimethylation (H3K4me3) and lysine 27 acetylation (H3K27ac). Upregulation of interferon alpha and gamma response and downregulation of c-MYC target genes, in function of c-MYC reduced expression (monitored in all the hematopoietic neoplasms tested), represent the most significant modulated pathways. These data demonstrate the ability of maltonis to epigenetically reprogram the gene expression profile of APL cells, inducing an intriguing antiviral-like response, concomitantly with the downregulation of c-MYC-related pathways, thus making it an attractive candidate for antileukemic therapy., (© 2022. The Author(s).)

Numerous athletes compete at a high level without consuming animal products; although a well-planned vegan diet might be appropriate for all stages of the life cycle, a few elements need to be addressed to build a balanced plant-based diet for an athlete, particularly in bodybuilding, in which muscle growth should be maximised, as athletes are judged on their aesthetics. In this observational study, nutritional intakes were compared in a cohort of natural omnivorous and vegan bodybuilders, during two different phases of preparation. To this end, 18 male and female bodybuilders (8 vegans and 10 omnivores) completed a food diary for 5 days during the bulking and cutting phases of their preparation. A mixed-model analysis was used to compare macro- and micronutrient intakes between the groups in the two phases. Both vegans and omnivores behaved similarly regarding energy, carbohydrate, and fat intakes, but vegans decreased their protein intake during the cutting phase. Our results suggest that vegan bodybuilders may find difficulties in reaching protein needs while undergoing a caloric deficit, and they might benefit from nutritional professionals' assistance to bridge the gap between the assumed proteins and those needed to maintain muscle mass through better nutrition and supplementation planning.

Introduction: Upper respiratory tract infections (URTI) are the most common illnesses affecting athletes, causing absences from training and competition. Salivary immunoglobulin A (sIgA) is the main immune factor in saliva, and a consistent association between low concentrations of sIgA and an increased incidence of URTIs has been reported. The oral probiotic Streptococcus salivarius K12 has been suggested to have the potential to improve oral diseases and mucosal barrier function. However, the effects of this probiotic on active young subjects performing a high-intensity training (HIT) program have not been investigated., Methods: Active young students were randomised into a treated group ( S. salivarius K12) and a control (placebo) group and asked to take the product daily for 30 days. After this period, participants performed a graded exercise test and five HIT sessions, all within 3 days. They were also asked to complete the Wisconsin Upper Respiratory Symptom Survey daily to monitor URTI's presence. Before and after the 30 days, and at 0h, 24h and 72h after the last training session, saliva samples were collected to quantify sIgA level, secretion rate, and flow. The effect of S. salivarius K12 intake on these parameters was tested using an ANOVA for repeated measures., Results: Twenty (M = 14, F = 6) young subjects (23.5 ± 2.3 years old) participated in the study. The total accumulated training load (sRPE) in the supplementation period was similar in the two groups (treated: 4345 ± 3441 AU; control: 4969 ± 4165 AU; p > 0.05). Considering both sIgA level and secretion rate, significant time (F (4,15) = 3.38; p = 0.037; F (4,15) = 6.00; p = 0.004) and time×group interactions (F (4,15) = 2.49; p = 0.049; F (4,15) = 5.01; p = 0.009) were reported, with the treated group showing higher sIgA levels at 72h post-exercise and increased secretion rate both at 0h and 72h. The number of URTI episodes was similar in the treated and control groups (χ² = 1.83; p > 0.05)., Conclusion: This study demonstrates that relatively short-term S. salivarius K12 supplementation increased sIgA level and secretion in healthy subjects performing a demanding exercise-training programme composed of HIT sessions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor FDP declared a past collaboration with the author AB., (Copyright © 2023 Bertuccioli, Gervasi, Annibalini, Binato, Perroni, Rocchi, Sisti and Amatori.)

Methyl-CpG binding protein 2 (MeCP2) is a ubiquitous transcriptional regulator. The study of this protein has been mainly focused on the central nervous system because alterations of its expression are associated with neurological disorders such as Rett syndrome. However, young patients with Rett syndrome also suffer from osteoporosis, suggesting a role of MeCP2 in the differentiation of human bone marrow mesenchymal stromal cells (hBMSCs), the precursors of osteoblasts and adipocytes. Here, we report an in vitro downregulation of MeCP2 in hBMSCs undergoing adipogenic differentiation (AD) and in adipocytes of human and rat bone marrow tissue samples. This modulation does not depend on MeCP2 DNA methylation nor on mRNA levels but on differentially expressed miRNAs during AD. MiRNA profiling revealed that miR-422a and miR-483-5p are upregulated in hBMSC-derived adipocytes compared to their precursors. MiR-483-5p, but not miR-422a, is also up-regulated in hBMSC-derived osteoblasts, suggesting a specific role of the latter in the adipogenic process. Experimental modulation of intracellular levels of miR-422a and miR-483-5p affected MeCP2 expression through direct interaction with its 3' UTR elements, and the adipogenic process. Accordingly, the knockdown of MeCP2 in hBMSCs through MeCP2-targeting shRNA lentiviral vectors increased the levels of adipogenesis-related genes. Finally, since adipocytes released a higher amount of miR-422a in culture medium compared to hBMSCs we analyzed the levels of circulating miR-422a in patients with osteoporosis-a condition characterized by increased marrow adiposity-demonstrating that its levels are negatively correlated with T- and Z-scores. Overall, our findings suggest that miR-422a has a role in hBMSC adipogenesis by downregulating MeCP2 and its circulating levels are associated with bone mass loss in primary osteoporosis., (© 2023. The Author(s).)

Background: Recent research suggest that gut microbiome may play a fundamental role in athlete's health and performance. Interestingly, nutrition can affect athletic performance by influencing the gut microbiome composition. Among different dietary patterns, ketogenic diet represents an efficient nutritional approach to get adequate body composition in athletes, however, some concerns have been raised about its potential detrimental effect on gut microbiome. To the best of our knowledge, only one study investigated the effect of ketogenic diet on the gut microbiome in athletes (elite race walkers), whilst no studies are available in a model of mixed endurance/power sport such as soccer. This study aimed to investigate the influence of a ketogenic Mediterranean diet with phytoextracts (KEMEPHY) diet on gut microbiome composition in a cohort of semi-professional soccer players., Methods: 16 male soccer players were randomly assigned to KEMEPHY diet (KDP n = 8) or western diet (WD n = 8). Body composition, performance measurements and gut microbiome composition were measured before and after 30 days of intervention by 16S rRNA amplicon sequencing. Alpha-diversity measures and PERMANOVA was used to investigate pre-post differences in the relative abundance of all taxonomic levels (from phylum to genus) and Spearman's correlations was used to investigate associations between microbial composition and macronutrient intake. Linear discriminant analysis was also performed at the different taxonomic levels on the post-intervention data., Results: No differences were found between pre and post- dietary intervention for microbial community diversity: no significant effects of time ( p = 0.056, ES = 0.486 and p = 0.129, ES = 0.388, respectively for OTUs number and Shannon's ENS), group ( p = 0.317, ES = 0.180 and p = 0.809, ES = 0.047) or time × group ( p = 0.999, ES = 0.01 and p = 0.230, ES = 0.315). Post-hoc paired Wilcoxon test showed a significant time × group effect for Actinobacteriota ( p = 0.021, ES = 0.578), which increased in the WD group (median pre: 1.7%; median post: 2.3%) and decreased in the KEMEPHY group (median pre: 4.3%; median post: 1.7%). At genus level, the linear discriminant analysis in the post intervention differentiated the two groups for Bifidobacterium genus (pertaining to the Actinobacteria phylum), Butyricicoccus and Acidaminococcus genera, all more abundant in the WD group, and for Clostridia UCG-014 (order, family, and genus), Butyricimonas, Odoribacterter genera (pertaining to the Marinifilaceae family), and Ruminococcus genus, all more abundant in the KEMEPHY group., Conclusions: Our results demonstrate that 30 days of KEMEPHY intervention, in contrast with previous research on ketogenic diet and gut microbiome, do not modify the overall composition of gut microbiome in a cohort of athletes. KEMEPHY dietary pattern may represent an alternative and safety tool for maintaining and/or regulating the composition of gut microbiome in athletes practicing regular exercise. Due to the fact that not all ketogenic diets are equal, we hypothesized that each version of ketogenic diet, with different kind of nutrients or macronutrients partitioning, may differently affect the human gut microbiome., Competing Interests: Author AP has received a research grant from Gianluca Mech S.p.A. Asigliano Veneto, Vicenza, Italy. Author LC is a Ph.D. student currently supported by a grant from Gianluca Mech SpA, Asigliano Veneto, Vicenza, Italy. The company had no role in the study design, data collection, data analysis, data interpretation, or writing of the article. Authors ES and LB were employed by BMR Genomics srl. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mancin, Amatori, Caprio, Sattin, Bertoldi, Cenci, Sisti, Bianco and Paoli.)

Body composition assessment is a relevant element in the biomedical field, in research and daily practice in the medical and nutritional fields, and in the management of athletes. This paper aimed to operate in an Italian sample investigating the possibility of predicting the somatotype from bioimpedance analysis and comparing the predicted results with those obtained from anthropometric measurements. This observational study was conducted with retrospective data collected from 2827 subjects. The somatotype of each subject was calculated both with the Heath−Carter method and by a multiple regression model based on bioimpedance and anthropometric parameters. Somatotypes (endomorph, mesomorph, and ectomorph) were predicted with a high goodness of fit (R2 adjusted > 0.80). Two different somatocharts were obtained from anthropometric measures and bioimpedance parameters and subsequentially compared. Bland−Altman plots showed acceptable accuracy. This study could be a first step in developing a new approach that allows the detection of a subject’s somatotype via bioimpedance analysis, stratified according to sex, with a time-saving and more standardized procedure. It would allow, for example, during the COVID-19 pandemic, to minimize operator−patient contact in having measurements.

The endeavor to evaluate the linearity of myofibrillar structures and their potential deviation from a straight line is a fascinating problem in muscle tissue image analysis. In this Letter, we suggest two different strategies for solving the same challenge. The first strategy is based on an alignment index, which could be derived by comparing the sum of the lengths of the individual sarcomeres with the distance between the "head" of the first and the "tail" of the last sarcomere. The second strategy relies on circular statistics, which takes a cue from an already suggested method. Our proposed methods are alternatives: the former has the advantage of simplicity; the latter is certainly more elegant and gives greater substance to statistical analysis, but in contrast, it also has greater computational complexity.

Bis(pyrazol-1-yl)acetic acid (HC(pz) 2 COOH) and bis(3,5-dimethyl-pyrazol-1-yl)acetic acid (HC(pz Me2 ) 2 COOH) were converted into the methyl ester derivatives 1 (L OMe ) and 2 (L 2OMe ), respectively, and were used for the preparation of Cu(I) and Cu(II) complexes 3 - 10 . The copper(II) complexes were prepared by the reaction of CuCl 2 ·2H 2 O or CuBr 2 with ligands 1 and 2 in methanol solution. The copper(I) complexes were prepared by the reaction of Cu[(CH 3 CN) 4 ]PF 6 and 1,3,5-triaza-7-phosphaadamantane (PTA) or triphenylphosphine with L OMe and L 2OMe in acetonitrile solution. Synchrotron radiation-based complementary techniques (XPS, NEXAFS, and XAS) were used to investigate the electronic and molecular structures of the complexes and the local structure around copper ions in selected Cu(I) and Cu(II) coordination compounds. All Cu(I) and Cu(II) complexes showed a significant in vitro antitumor activity, proving to be more effective than the reference drug cisplatin in a panel of human cancer cell lines, and were able to overcome cisplatin resistance. Noticeably, Cu complexes appeared much more effective than cisplatin in 3D spheroid cultures. Mechanistic studies revealed that the antitumor potential did not correlate with cellular accumulation but was consistent with intracellular targeting of PDI, ER stress, and paraptotic cell death induction.

To detect the epigenetic drift of time passing, we determined the genome-wide distributions of mono- and tri-methylated lysine 4 and acetylated and tri-methylated lysine 27 of histone H3 in the livers of healthy 3, 6 and 12 months old C57BL/6 mice. The comparison of different age profiles of histone H3 marks revealed global redistribution of histone H3 modifications with time, in particular in intergenic regions and near transcription start sites, as well as altered correlation between the profiles of different histone modifications. Moreover, feeding mice with caloric restriction diet, a treatment known to retard aging, reduced the extent of changes occurring during the first year of life in these genomic regions.

Numerous factors, ranging from genetics, age, lifestyle, and dietary habits to local environments, contribute to the heterogeneity of the microbiota in humans. Understanding the variability of a "healthy microbiota" is a major challenge in scientific research. The gut microbiota profiles of 148 healthy Italian volunteers were examined by 16S rRNA gene sequencing to determine the range and diversity of taxonomic compositions in the gut microbiota of healthy populations. Possible driving factors were evaluated through a detailed anamnestic questionnaire. Microbiota reference intervals were also calculated. A "scaffold" of a healthy Italian gut microbiota composition was identified. Differences in relative quantitative ratios of microbiota composition were detected in two clusters: a bigger cluster (C 2 ), which included 124 subjects, was characterized by more people from the northern Italian regions, who habitually practised more physical activity and with fewer dietary restrictions. Species richness and diversity were significantly higher in this cluster (C 2 ) than in the other one (C 1 ) (C 1 : 146.67 ± 43.67; C 2 : 198.17 ± 48.47; F = 23.40; P < 0.001 and C 1 : 16.88 ± 8.66; C 2 : 35.01 ± 13.40; F = 40.50; P < 0.001, respectively). The main contribution of the present study was the identification of the existence of a primary healthy microbiological framework that is only marginally affected by variations. Taken together, our data help to contextualize studies on population-specific variations, including marginal aspects, in human microbiota composition. Such variations must be related to the primary framework of a healthy microbiota and providing this perspective could help scientists to better design experimental plans and develop strategies for precision tailored microbiota modulation., (© 2022. The Author(s).)