Advanced Maturation Research Articles

Mutating alfalfa COUMARATE 3-HYDROXYLASE using multiplex CRISPR/Cas9 leads to reduced lignin deposition and improved forage quality.

Alfalfa (Medicago sativa L.) forage quality is adversely affected by lignin deposition in cell walls at advanced maturity stages. Reducing lignin content through RNA interference or antisense approaches has been shown to improve alfalfa forage quality and digestibility. We employed a multiplex CRISPR/Cas9-mediated gene-editing system to reduce lignin content and alter lignin composition in alfalfa by targeting the COUMARATE 3-HYDROXYLASE (MsC3H) gene, which encodes a key enzyme in lignin biosynthesis. Four guide RNAs (gRNAs) targeting the first exon of MsC3H were designed and clustered into a tRNA-gRNA polycistronic system and introduced into tetraploid alfalfa via Agrobacterium-mediated transformation. Out of 130 transgenic lines, at least 73 lines were confirmed to contain gene-editing events in one or more alleles of MsC3H. Fifty-five lines were selected for lignin content/composition analysis. Amongst these lines, three independent tetra-allelic homozygous lines (Msc3h-013, Msc3h-121, and Msc3h-158) with different mutation events in MsC3H were characterized in detail. Homozygous mutation of MsC3H in these three lines significantly reduced the lignin content and altered lignin composition in stems. Moreover, these lines had significantly lower levels of acid detergent fiber and neutral detergent fiber as well as higher levels of total digestible nutrients, relative feed values, and in vitro true dry matter digestibility. Taken together, these results showed that CRISPR/Cas9-mediated editing of MsC3H successfully reduced shoot lignin content, improved digestibility, and nutritional values without sacrificing plant growth and biomass yield. These lines could be used in alfalfa breeding programs to generate elite transgene-free alfalfa cultivars with reduced lignin and improved forage quality.

UREA TREATMENT OF MATURE WHOLE-CROP CEREAL MIXTURES AS SALVAGE FORAGE FOR SMALL-SCALE DAIRY SYSTEMS IN THE DRY SEASON

<p><strong>Background:</strong> Forage from small-grain cereals is an option to diversify feeding strategies in small-scale dairy systems (SSDS), due to their short cycle and ample adaptation. Mixtures of cereal species may have synergic advantages; however, grazing or ensiling is not always possible due to climatic factors, so forage crops are left to mature and lose quality. Urea treatment of whole-crop mature cereal mixtures may be an option to salvage forage that could not be grazed or ensiled. <strong>Objective:</strong> To evaluate the performance of dairy cows fed urea-treated mature whole-crop forage mixtures of triticale (TRT), rye (RYE), and barley (BLY), in the dry season for SSDS. <strong>Methodology</strong>: Treatment mixtures were TRT+RYE, TRT-BLY, and RYE+BLY. Fully mature cereal mixture crops were treated with 4 - 6% granular urea (plus water) on a fresh basis. Forage variables were analysed with a split-plot design. Whole-crop forage yields were 3.4 ton/ha, with highest yields for RYE-BLY. Crude protein content increased two-fold in treated forages, and dry matter digestibility was moderate with a mean estimated ME content of 7.9 MJ ME/kg DM. Performance was evaluated by an on-farm 3x3 Latin square experimental design repeated 3 times with nine Holstein cows, experimental periods were 14 days, of which 10 days were for adaptation to feeding and 4 days for sampling. Cows were offered daily 9.0 kg DM of urea-treated forage; complemented with 4.4 kg DM of concentrate, day-grazing, and 1.5 kg of cut pasture. <strong>Results: </strong>There were no statistical differences (P>0.05) for any of the animal variables. Urea treatment of whole-crop mature cereal mixtures resulted in a complementary moderate quality salvage forage for the dry season. <strong>Implications:</strong> The present study is presented as an alternative when the crops are in a state of advanced maturation and it is intended to modify the nutritional quality of the forages. <strong>Conclusion:</strong> The use of urea can be an alternative to improve the nutritional quality of forages.</p>

Advances and Challenges in Cerebral Organoids Research

Cerebral organoids are three‐dimensional (3D) aggregates with a more advanced composition, maturation, and architecture. It has emerged as a novel and sophisticated model system for studying neurodevelopment and neurological disorders, in comparison to conventional two‐dimensional (2D) cell cultures. However, due to the extraordinarily complex nature of brain development, current cerebral organoids are not as functional and mature as brains. The development of cerebral organoids requires a culture system with sufficient developmental patterning factors, essential cell components, and vasculature. In this review, the critical factors and events that contribute to the development of cerebral organoids are focused on. The advanced design, fabrication techniques, and technologies are also discussed to enhance the application potential of cerebral organoid technology.

Who Reaches the NHL? A 20-Year Retrospective Analysis of Junior and Adult Ice Hockey Success in Relation to Biological Maturation in Male Swedish Players

ObjectivesThis study investigated the relationship between biological maturation and success in adolescence and adulthood in male Swedish ice hockey players.MethodsAnthropometric records of players in certified ice hockey high schools between 1998 and 2017 were retrieved (n = 4787). The database was complemented with records of Swedish junior national teams (U16, U18, U20) and National Hockey League (NHL) appearances. Biological maturation was recorded as a percentage of adult height (%AH), and selection probabilities were estimated using a generalised linear mixed effects model. Biological age was determined by comparing players with age-matched growth reference values. Categories of %AH, standard deviation z-scores and biological age offset describing early, on-time and late maturation were created.ResultsA total of 217 players had played on the U16 national team (junior success), and 96 reached the NHL (adult success). The difference [95% confidence interval (CI)] in baseline %AH between players with junior versus adult success was − 0.75 (− 0.39, − 1.11). Looking at age-offset categories in junior success, 30% of players were early maturing and 19% of players were late maturing, showing a bias towards early maturation (p < 0.01). In contrast, more late-maturing players (40%) achieved adult success than early-maturing players (25%), and NHL players had significantly later maturation [%AH: − 0.48 (− 0.80, − 0.16)] than non-NHL players.ConclusionThis unique 20-year analysis shows that junior success in male ice hockey is positively related to early maturation, while adult success is inversely related to advanced maturation. Ice hockey organisations should implement maturation assessments to optimise the development of both late- and early-matured players.

Ontogenetic changes in the tyrosine hydroxylase immunoreactive preoptic area in the small-spotted catshark Scyliorhinus canicula (L., 1758) females: catecholaminergic involvement in sexual maturation.

The catecholaminergic component of the brain-pituitary-gonadal axis, which mediates the influence of external and internal stimuli on the central nervous system and gonad development in vertebrates, is largely unexplored in Chondrichthyes. We considered Scyliorhinus canicula (L., 1758) females as a model for this vertebrate's class, to assess the involvement of the catecholaminergic system of the brain in its reproduction. Along the S. canicula reproductive cycle, we characterized and evaluated differences in somata morphometry and the number of putative catecholaminergic neurons in two brain nuclei: the periventricular preoptic nucleus, hypothesized to be a positive control for ovarian development, and the suprachiasmatic nucleus, examined as a negative control. 16 S. canicula wild females were sampled and grouped in maturity stages (immature, maturing, mature, and mature egg-laying). The ovary was histologically processed for the qualitative description of maturity stages. Anti-tyrosine hydroxylase immunofluorescence was performed on the diencephalic brain sections. The immunoreactive somata were investigated for morphometry and counted using the optical fractionator method, throughout the confocal microscopy. Qualitative and quantitative research confirmed two separate populations of immunoreactive neurons. The modifications detected in the preoptic nucleus revealed that somata were more numerous, significantly smaller in size, and more excitable during the maturing phase but decreased, becoming slightly bigger and less excitable in the egg-laying stage. This may indicate that the catecholaminergic preoptic nucleus is involved in the control of reproduction, regulating both the onset of puberty and the imminent spawning. In contrast, somata in the suprachiasmatic nucleus grew in size and underwent turnover in morphometry, increasing the total number from the immature-virgin to maturing stage, with similar values in the more advanced maturity stages. These changes were not linked to a reproductive role. These findings provide new valuable information on Chondrichthyes, suggesting the existence of an additional brain system implicated in the integration of internal and environmental cues for reproduction.

Reflective groundcovers promote anthocyanin content and advance fruit maturity of 'Evercrisp' apples grown in the Mid-Atlantic US.

Enhanced skin blush is critical in many apple cultivars to ensure crop profitability and acceptability. Anthocyanin content is a crucial determinant of apple skin blush. Reflective groundcovers are a preharvest management strategy that can improve apple skin blush, but integrative studies assessing its effects at the environmental, physiological, gene, and metabolite levels are lacking. In the present study, we assessed the impact of reflective groundcovers on light environment, preharvest fruit drop, internal ethylene concentration (IEC), fruit-quality-related physicochemical parameters, skin coloration, expression levels of important anthocyanin biosynthesis-related structural genes and transcription factors, and total anthocyanin content of 'Evercrisp' fruit located in the canopy's lower third during on-the-tree ripening, for 2 years, under mid-Atlantic US conditions. Fruit treated with reflective groundcovers displayed an enhanced red skin coloration, reaching >60% blush 1 week before commercial harvest and 2 weeks earlier than control fruit. This resulted from a significantly increased transcript accumulation of anthocyanin biosynthesis-assessed genes, which was promoted by an increased light reflectance (>5-25 times greater than control), which also led to a correspondingly higher total anthocyanin content. Additionally, reflective groundcover-treated 'Evercrisp' fruit also exhibited an increased IEC and an advanced maturity, but without differences in fruit drop, as compared to control fruit, during on-the-tree ripening. Reflective groundcovers deployment would allow for an earlier harvest (of at least one week) of 'Evercrisp' fruit, which would be packing out in the premium grades as compared to control, thus increasing fruit crop value.

Digital Maturity as a Strategy for Advancing Patient Experience in US Hospitals.

Patient experience is globally recognized as an important indicator of health system performance, linked to health system quality and improving patient outcomes. Post COVID-19, health systems have embraced digital health and advanced digital transformation efforts; however, the relationship between digital health and patient experience outcomes is not well-documented. Using HCAHPS hospital survey data to measure patient experience, and HIMSS EMRAM Maturity Model data to measure digital maturity, a cross-sectional design using multivariate analyses examined the impact of digital maturity on patient experience in US hospitals. Our analysis shows that advanced digital maturity in US hospitals is associated with stronger patient experience outcomes, particularly relative to communication with nurses, doctors, and communication about medicines and therapies. The findings suggest that there are significant differences in patient experience associated with teaching versus nonteaching hospitals, urban versus rural hospitals. As hospitals advance and progress digital transformation initiatives, evidence to inform how transformation efforts can engage and advance patient experience will contribute to health system performance well into the future.

Secular changes in dental development of Korean children aged 4 to 16 years over a 10-year period.

This study evaluated 10-year secular changes in dental maturity and dental development among Korean children. A retrospective analysis of panoramic radiograph samples from Korean children (4-16 years old) taken in 2010 and 2020 was conducted. The 2010 group consisted of 3491 radiographs (1970 boys and 1521 girls), and the 2020 group included 5133 radiographs (2825 boys and 2308 girls). Using Demirjian's method, dental maturity scores and dental developmental stages were assessed. For intra-observer reliability, Weighted Cohen's kappa was used, and Mann-Whitney U tests were performed to compare the 2020 and 2010 groups. A slight acceleration in dental maturity was observed in both boys and girls, with the difference being more noticeable in boys at an earlier age. Statistically significant differences were noted at ages 4, 5 and 7 for boys, and at age 6 for girls. Despite these differences, the individual dental development stages of 2020 and 2010 showed inconsistent trends with limited differences. Generally, girls demonstrate more advanced dental maturity than boys. A slight acceleration in Korean children's dental maturity was observed over a 10-year period when comparing the 2020 groups to the 2010 groups.

Ages at peak height velocity in male soccer players 11-16 years: relationships with skeletal age and comparisons among longitudinal studies.

Estimated ages at take-off (TO) and at peak height velocity (PHV) based on two models and maturity status based upon age at PHV and skeletal age (SA) were compared in a longitudinal sample of male soccer players. In addition, estimated ages at PHV in 13 longitudinal samples of soccer players were compared. The longitudinal height records of 58 players of European ancestry, measured annually on four or five occasions between 11 and 16 years, were modeled with Superimposition by Translation and Rotation (SITAR) and Functional Principal Component Analysis (FPCA) to estimate ages at TO and PHV. SAs were assessed with the Fels method. Ages at PHV in 13 longitudinal samples of soccer players (Europe 7, Japan 6) were evaluated with meta-analysis. Estimated ages at TO, 11.2 ± 0.8 (SITAR) and 11.0 ± 0.8 (FCPA) years, and at PHV, 13.6 ± 0.9 (SITAR) and 13.7 ± 0.0 (FCPA) years, were similar. An earlier age at PHV was associated with advanced skeletal maturity status (rho = -0.77 at ~14 years). Ages at PHV among European players indicated a north (later) - south (earlier) gradient, and were later than ages at PHV among Japanese players. In summary, ages at TO and PHV were similar with SITAR and FPCA, and ages at PHV were most strongly correlated with SA at ~14 years. Mean ages at PHV showed a north-south gradient among European samples, and were later compared to Japanese samples.

Growth, body composition, and endocrine-metabolic profiles of individuals with Kleefstra syndrome provide directions for clinical management and translational studies.

Mendelian neurodevelopmental disorders caused by variants in genes encoding chromatin modification can be categorized as Mendelian disorders of the epigenetic machinery (MDEMs). These disorders have significant overlap in molecular pathways and phenotypes including intellectual disability, short stature, and obesity. Among the MDEMs is Kleefstra syndrome (KLFS), which is caused by haploinsufficiency of EHMT1. Preclinical studies have identified metabolic dysregulation and obesity in KLFS models, but proper clinical translation lacks. In this study, we aim to delineate growth, body composition, and endocrine-metabolic characteristics in a total of 62 individuals with KLFS. Our results revealed a high prevalence of childhood-onset overweight/obesity (60%; 28/47) with disproportionately high body fat percentage, which aligns perfectly with previous preclinical studies. Short stature was common (33%), likely due to advanced skeletal maturation. Endocrine-metabolic investigations showed thyroid dysregulation (22%; 9/41), elevated triglycerides, and decreased blood ammonia levels. Moreover, hand radiographs identified decreased bone mineralization (57%; 8/14) and negative ulnar variance (71%; 10/14). Our findings indicate a high (cardio)metabolic risk in KLFS. Therefore, we recommend monitoring of weight and endocrine-metabolic profile. Supporting a healthy lifestyle and screening of bone mineralization is advised. Our comprehensive results support translational research and contribute to a better understanding of MDEM-associated phenotypes.

Usability Evaluation and Enhancement of the AI-Powered Smart-Campus Framework: A User-Centred Approach

This study employs a user-centred approach to improving the user experience and maximizing the system functionality of an AI-powered smart-campus framework. The study aims to conduct the usability evaluation of the framework and identify areas for improvement. The focus areas include AI-powered features, user interactions, and design concepts. The study used Likert scale evaluations to measure user satisfaction and perceived usability. The identification and application of improvement measures resulted in positive outcomes. The feedback integration technique involves collecting and analyzing user feedback to identify areas for improvement. This feedback is then used to make iterative improvements to the framework. The study found that the feedback integration technique increased user happiness through iterative improvements. The redesign valve interface strategy involves redesigning the valve interface to make it more user-friendly. The study found that the redesign valve interface strategy raised perceived usability. Workflow optimization involves streamlining the workflow to make it more efficient. The study found that workflow optimization reduced completion times. The study used the UMM to evaluate the planning, design, implementation, and feedback aspects of the AI-powered smart-campus framework. The study found that the framework had advanced design maturity, indicating good integration of user personas and workflows. The framework also showed intermediate maturity in planning, with consistency in implementation but space for improvement. The study also highlighted the theoretical connections between UMM dimensions and quantitative metrics. This alignment between qualitative principles and quantitative measures is important for demonstrating the value of user-centred design.

Non-specific and ski-specific performance development in peri-pubertal cross-country skiers.

To evaluate non-specific and ski-specific performance development in male (M) and female (F) peri-pubertal cross-country skiers and to evaluate their relationship with cross-country skiing (XCS) performance and biological maturation within each age category and sex. Twenty-one and 19 athletes under 14 and 16years old, respectively (U14 and U16), were tested for biological maturation; non-specific speed, agility, strength, endurance, and balance; ski-specific speed, agility, and endurance. XCS index was considered as average percentage time-gap from the winner in four official races. Sex and age-category effects were verified and a model predicting XCS index was extrapolated for each group. Performance capacities raised across age categories (p < 0.05) except for non-specific speed, agility, balance, and relative arm strength (p > 0.05). F showed advanced biological maturation and greater balance than M (p < 0.05), while M showed higher performance capacities (p < 0.05). XCS index was not related to biological maturation within each group (p > 0.05); its variance was explained by non-specific speed and ski-specific upper-body endurance in M-U14 (p = 0.014), lower-limb strength and ski-specific agility in M-U16 and F-U14 (both p = 0.001), ski-specific upper-body endurance in F-U16 (p = 0.002). Ski-specific performance capacities still develop during peri-puberty, with peri-pubertal M overperforming with respect to F of comparable performance level. XCS index was not influenced by biological maturation withing each age category, but it was rather explained by specific parameters that commonly undergo the "adolescent spurts", accordingly to the average biological maturation level of M and F athletes of each age category.

Scaffolded spheroids as building blocks for bottom-up cartilage tissue engineering show enhanced bioassembly dynamics

Due to the capability of cell spheroids (SPH) to assemble into large high cell density constructs, their use as building blocks attracted a lot of attention in the field of biofabrication. Nevertheless, upon maturation, the composition along with the size of such building blocks change, affecting their fusiogenic ability to form a cohesive tissue construct of controllable size. This natural phenomenon remains a limitation for the standardization of spheroid-based therapies in the clinical setting.We recently showed that scaffolded spheroids (S-SPH) can be produced by forming spheroids directly within porous PCL-based microscaffolds fabricated using multiphoton lithography (MPL). In this new study, we compare the bioassembly potential of conventional SPHs versus S-SPHs depending on their degree of maturation. Doublets of both types of building blocks were cultured and their fusiogenicity was compared by measuring the intersphere angle, the length of the fusing spheroid pairs (referred to as doublet length) as well as their spreading behaviour. Finally, the possibility to fabricate macro-sized tissue constructs (i.e. cartilage-like) from both chondrogenic S-SPHs and SPHs was analyzed.This study revealed that, in contrast to conventional SPHs, S-SPHs exhibit robust and stable fusiogenicity, independently from their degree of maturation. In order to understand this behavior, we further analyze the intersection area of doublets, looking at the kinetic of cell migration and at the mechanical stability of the formed tissue using dissection measurements. Our findings indicate that the presence of microscaffolds enhances the ability of spheroids to be used as building blocks for bottom-up tissue engineering, which is an important advantage compared to conventional spheroid-based therapy approaches. Statement of significanceThe approach of using SPHs as building blocks for bottom-up tissue engineering offers a variety of advantages. At the same time the self-assembly of large tissues remains challenging due to several intrinsic properties of SPHs, such as for instance the shrinkage of tissues assembled from SPHs, or the reduced fusiogenicity commonly observed with mature SPHs. In this work, we demonstrate the capability of scaffolded spheroids (S-SPH) to fuse and recreate cartilage-like tissue constructs despite their advanced maturation stage. In this regard, the presence of microscaffolds compensates for some of the intrinsic limitations of SPHs and can help to overcome current limitations of spheroid-based tissue engineering.

Tangle and neuritic burden from neurofibrillary tangle maturity markers in the hippocampus are differentially correlated to tau‐PET, MRI, and cognitive measures

AbstractBackgroundThere is a gap in knowledge concerning which tangle maturity levels (Moloney, Alzheimers Dement, 2021) are associated with antemortem measures (tau‐PET, MRI, cognitive testing). We hypothesized antemortem measures would be more strongly correlated with markers recognizing middling to advanced tangle maturity. We additionally sought to assess the strength of the relationship with tangle and neuritic pathology recognized by tangle maturity markers.MethodPosterior hippocampi from n = 30 cases with antemortem measures ≤3 years prior to death were cut (5µm) and immunostained with tau antibodies to evaluate early (AT8), middling (PHF‐1), or advanced (2E9) tangle maturity. GENIE (pattern recognition software) separated tangle from neuritic burden (Figure). Hippocampus, parahippocampus, and fusiform were analyzed to correlate digital pathology with flortaucipir tau‐PET standard uptake value ratio (SUVr, cerebellar crus normalization), MRI volume/thickness, and cognitive measures which included Auditory Verbal Learning Test (AVLT) delayed recall, Mini‐Mental State Exam (MMSE), and Clinical Dementia Rating (CDR).ResultThe strongest relationships observed with flortaucipir were with PHF‐1 and 2E9 burden (Table). AT8 tangle and neuritic burden correlations with flortaucipir were relatively similar in the hippocampus but were stronger with neuritic pathology in parahippocampus and fusiform. PHF‐1 tangle and neuritic burden correlations were relatively similar with flortaucipir. 2E9 correlations were stronger with neuritic pathology in hippocampus. MRI measures were more strongly correlated with PHF‐1 and 2E9 burden. AT8 tangle and neuritic burden were correlated with fusiform thickness. The correlations between MRI measures and 2E9 tangle and neuritic burden were similar. Correlations between cognitive measures were similar between tangle maturity markers. AVLT delayed recall correlated with all tangle maturity markers, but neuritic burden was stronger for AT8 and 2E9 in hippocampus compared to tangle burden. MMSE correlated with neuritic burden for all tangle maturity markers. CDR remained statistically non‐significant.ConclusionInterpretation of the strength of the relationship between tau burden and antemortem measures differed across tangle maturity markers. Neuroimaging measures may be more sensitive to middle/advanced maturity markers with limited differences between tangle and neuritic pathology. These findings may be biologically relevant and imply either a limited recognition of tangles depending on antibody epitope, and/or may represent the clinicoradiologic impact of increasing neuritic burden.

Biofloc technology application in Nile tilapia (Oreochromis niloticus, L.) hatcheries: effect on the reproductive performance, offspring quality, growth performance, and physiological parameters of fry

ABSTRACT This study evaluated the potential of applying biofloc technology (BFT) in Nile tilapia (Oreochromis niloticus) hatcheries. The first experiment was conducted to determine the effect of maintaining tilapia broodstock in BFT system in terms of reproductive performance and offspring quality as compared with the conventional clear-water system. A total of 45-tilapia broodstock were reared for 2 months in each treatment. Females at advanced maturation were transferred to four spawning tanks (800 L) at a density of eight individuals per tank (3:1 female:male sex ratio). Two tanks were assigned to each of the two treatments (BFT and control). Reproduction took place over the course of 2 months, with all females being inspected weekly to verify the presence of eggs. The second trial (43 days) analyzed the effect of BFT system on growth performance, feed utilization, digestive enzymes activity, and antioxidant status in the early fry stages. A total of 540 larvae (8.7 ± 0.7 mg) were assigned to six glass aquariums (60 L capacity). One experimental group was reared using a BFT system with daily sugar addition at a C/N ratio of 15/1, in comparison to a control group reared in clear water. Fish were fed commercial pellets three times a day at various feeding ratios (6–9% of the fish body weight). The fecundity of tilapia, hatching rate, egg and larval size, and larval resistance to stress tests presented no significant differences among treatments (P > .05). After 20 days of larval rearing, the daily weight gain was 29% higher in BFT fish as compared to the control treatment. The BFT system had better feed conversion ratio than control treatment. The larvae reared in BFT system had significantly higher alpha-amylase and catalase activities than control (P < .05). Overall, these results suggest that the BFT system can be used in tilapia hatcheries for broodstock rearing without negative effects on reproductive performance. The better growth performances of larvae reared in BFT treatment justified the application of this system during nursery phase.

How pubertal timing and self-regulation predict adolescent sexual activity in resource-poor environments.

Studies found support for a link between pubertal timing and self-regulation in low-resource environments. This link could potentially explain a link between pubertal timing and early risk behavior. This study builds on this body of research by examining the mediated effect of pubertal timing on sexual activity through self-regulation in 728 adolescents and their families in a group with poor resources and a group with adequate resources. Income-to-Needs (ITN) was measured at age 7.5 to establish two groups (low-ITN and Medium/High-ITN). Pubertal timing was measured at age 10.5, self-regulation was assessed at age 14 and operationalized with effortful control, and sexual activity was assessed at age 16. Structural equation modeling was employed to test the hypothesized model in both groups. The link between pubertal timing and sexual activity mediated by effortful control was only significant in the low-ITN group. Specifically, more advanced pubertal maturity was associated with lower levels of adolescents' effortful control, which in turn was associated with more sexual activity at age 16. Findings were partially replicated with a drug use index replacing sexual activity. This study shows a different operating link from pubertal timing to effortful control and subsequent risk behavior in resource-poor environments. Implications are discussed.

Role of muscle mass in the association between handgrip strength and blood pressure in children and adolescents.

Studies have reported conflicting results on the association between handgrip strength (HGS) and blood pressure during childhood and adolescence. High multicollinearity involving somatic components that influence both HGS and blood pressure might be an important source of bias. This study sought to investigate the independent effects of HGS and muscle mass on blood pressure levels in children and adolescents. Muscle mass and fat mass (Multifrequency Electrical Bioimpedance) and systolic (SBP) and diastolic (DBP) blood pressure (Automatic oscillometric device) were assessed in 833 volunteers aged 6-18 years, of both sexes. Handgrip strength-for-age quartiles were calculated and participants were assigned to groups by HGS quartiles. Analysis of covariance was conducted to address the linear association between HGS and SBP adjusted for height, muscle mass, and fat mass. To test for linear trend, contrast analysis was conducted. Partial eta-squared was used to confirm or rule out a small significant effect of the independent variables on SBP. The effect size of HGS on SBP was not significant in both sexes. In girls, 1.7% of the between-groups variance in SBP was accounted for by muscle mass (P = 0.016). In boys, 2.3% and 1.8% of the between-groups variance in SBP was accounted for by muscle mass (P = 0.001) and height (P = 0.005), respectively. In conclusion, children with a more advanced physical maturity for their age, that is, who are taller, stronger, and have greater fat-free mass, may be nearly reaching the physiological parameters of adulthood, and consequently have higher systolic blood pressure.

Deciphering the implications of mitophagy-related signatures in clinical outcomes and microenvironment heterogeneity of clear cell renal cell carcinoma.

The role of mitophagy in various cancer-associated biological processes is well recognized. Nonetheless, the comprehensive implications of mitophagy in clear cell renal cell carcinoma (ccRCC) necessitate further exploration. Based on the transcriptomic data encompassing 25 mitophagy-related genes (MRGs), we identified the distinct mitophage patterns in 763 ccRCC samples. Subsequently, a mitophage-related predictive signature with machine learning algorithms was constructed, designated as RiskScore, to quantify the individual mitophagy status in ccRCC patients. Employing multispectral immunofluorescence (mIF) and immunohistochemistry (IHC) staining, we detected the effect of PTEN-induced putative kinase 1 (PINK1) in the prognosis and immune microenvironment of ccRCC. Our analysis initially encompassed a comprehensive assessment of the expression profiling, genomic variations, and interactions among the 25 MRGs in ccRCC. Subsequently, the consensus clustering algorithm was applied to stratify ccRCC patients into three clusters with distinct prognostic outcomes, tumor microenvironment (TME) characteristics, and underlying biological pathways. We screened eight pivotal genes (CLIC4, PTPRB, SLC16A12, ENPP5, FLRT3, HRH2, PDK4, and SCD5) to construct a mitophagy-related predictive signature, which showed excellent prognostic value for ccRCC patients. Moreover, patient subgroups divided by the RiskScore showed contrasting expression levels of immune checkpoints (ICPs), abundance of immune cells, and immunotherapy response. Additionally, a nomogram was established with robust predictive power integrating the RiskScore and clinical features. Notably, we observed that PINK1 expression markedly correlated with favorable treatment response and advanced maturation stages of tertiary lymphoid structures, which potentially shed light on enhancing anti-tumor immunity of ccRCC. Collectively, this study initially developed a signature associated with mitophagy, which demonstrated an excellent ability to predict the clinical prognosis, TME characterization, and responsiveness to targeted therapy and immunotherapy for ccRCC patients. Of particular note is the pivotal role of PINK1 in mediating the treatment response and immune microenvironment for ccRCC patients.

The Intercultural Experience Project: A practical tool leveraging multiple intercultural experiences at home to foster student intercultural competence

ABSTRACT This paper reports on an Intercultural Experience Project that higher education institutions could implement to foster student intercultural competence (ICC) without the need for cross-border mobility. The project requires students to engage in multiple, direct and indirect, interpersonal and non-personal experiences with a foreign culture while keeping a journal of their interactions. It guides students in writing a cultural essay, analysing both their own and the foreign culture as well as the distance between them, then a reflective essay on their ICC learning. Analysis of student journals and essays corroborates that the project fostered student ICC attitudes, skills, knowledge, and awareness, even leading some students to advanced intercultural maturity levels. The multiplicity of intercultural interactions enhanced the meaningfulness and depth of students’ experience, emboldened them to engage in various types of interactions, and helped them develop advanced ICC skills related to comparative, critical, and systemic thinking.

TRANSCENDING BORDERS DIGITALLY: HOW REGIONAL POLICIES SUPPORTING SOCIAL ENTREPRENEURSHIP MEDIATE EXPORT RESILIENCE?

This study investigates the complex relationship between digital transformation, regional policies, and export resilience, with a specific focus on how social entrepreneurship factors into this dynamic. The research aimed to determine how these elements collectively shape a region’s adaptability and competitiveness in the global export market. Key findings indicate that digital transformation significantly enhances export resilience, as regions with advanced digital maturity exhibit greater agility and competitiveness during market disruptions. Moreover, regional policies play a pivotal mediating role by creating an environment conducive for businesses to adopt digital technologies and promote collaboration and innovation. The study also revealed that social entrepreneurship represents a valuable means of improving export resilience through digital transformation, as social enterprises can leverage technologies to expand opportunities while generating social impact. However, realizing this potential requires regional policies aimed at supporting social entrepreneurs with resources for digital skills development and technology adoption. Overall, the research underscores the need for a comprehensive strategy integrating technology adoption, supportive policies, and promotion of social entrepreneurship to reinforce a region’s capability to successfully navigate market disruptions and achieve resilient, sustainable export growth.