Search Results (1,504)

Background: The causation of type 2 diabetes remains under debate, but evidence supports both abdominal lipid and ectopic lipid overspill into tissues including muscle as key. How these depots differentially alter cardiometabolic profile and change during body weight and fat loss is not known. Methods: Women with obesity scheduled to undergo bariatric surgery were assessed at baseline (BL, n = 28) and at 6-month follow-up (6m_FU, n = 26) after weight loss. Fasting plasma (Pla), subcutaneous thigh adipose (STA), subcutaneous abdominal adipose, (SAA), and thigh vastus lateralis muscle (VLM) samples were collected at BL through surgery and at 6m_FU using needle biopsy. An untargeted liquid chromatography mass spectrometry metabolomics platform was used. Pla and tissue-specific lipid and polar metabolite profiles were modelled as changes from BL and 6m_FU. Results: There was significant body weight (−24.5 kg) loss at 6m_FU (p < 0.05). BL vs. 6m_FU tissue metabolomics profiles showed the largest difference in lipid profiles in SAA tissue in response to surgery. Conversely, polar metabolites were more susceptible to change in STA and VLM. In Pla samples, both lipid and polar metabolite profiles showed significant differences between timepoints. Jaccard–Tanimoto coefficient t-tests identified a sub-group of gut microbiome and dietary-derived omega-3-fatty-acid-containing lipid species and core energy metabolism and adipose catabolism-associated polar metabolites that are trafficked between sample types in response to bariatric surgery. Conclusions: In this first report on channelling of lipids and polar metabolites to alternative tissues in bariatric-induced weight loss, adaptive shuttling of small molecules was identified, further promoting adipose processing and highlighting the dynamic and coordinated nature of post-surgical metabolic regulation. Full article

Transportation is often cited as a significant barrier to healthcare access by Veterans, particularly those from minority groups, who have disabilities, or live in rural areas. Autonomous shuttles (AS) offer a potential solution, yet limited research has explored Veterans’ experiences with this technology. This study qualitatively investigated Veterans’ lived experiences with AS through focus groups, enrolling participants aged 18+ from Gainesville, The Villages, and Lake Nona, Florida. Via a directed content analysis, six key themes were identified: Perceived Benefits, Safety, Experience with Autonomous Vehicles (AV), AS Experience, AV Adoption, and Perception Change. Among 26 participants (aged 30–85; 77% men; 88% urban residents), prominent themes included Safety (n = 161), Perceived Benefits (n = 153), and AS Experience (n = 118), with predominantly positive counts in all themes except AS Experience. Participants acknowledged safety advantages and multitasking potential of AS over human-operated vehicles while recommending improvements to the shuttle’s slow speed, availability and convenience. While the AS ride was positively received overall, some participants noted issues with comfort and braking, emphasizing the need for further technological enhancements. Real-world exposure to AS appeared to influence acceptance positively, offering insights for policymakers and industry stakeholders aiming to optimize AS deployment for mobility-vulnerable Veterans. Full article

This review surveys recent advances and emerging prospects in phase-transfer catalysis (PTC) for fuel desulfurization. In response to increasingly stringent environmental regulations, the removal of sulfur from transportation fuels has become imperative for curbing SO_x emissions. Conventional hydrodesulfurization (HDS) operates under severe temperature–pressure conditions and displays limited efficacy toward sterically hindered thiophenic compounds, motivating the exploration of non-hydrogen routes such as oxidative desulfurization (ODS). Within ODS, PTC offers distinctive benefits by shuttling reactants across immiscible phases, thereby enhancing reaction rates and selectivity. In particular, PTC enables efficient migration of organosulfur substrates from the hydrocarbon matrix into an aqueous phase where they are oxidized and subsequently extracted. The review first summarizes the deployment of classic PTC systems—quaternary ammonium salts, crown ethers, and related agents—in ODS operations and then delineates the underlying phase-transfer mechanisms, encompassing reaction-controlled, thermally triggered, photo-responsive, and pH-sensitive cycles. Attention is next directed to a new generation of catalysts, including quaternary-ammonium polyoxometalates, imidazolium-substituted polyoxometalates, and ionic-liquid-based hybrids. Their tailored architectures, catalytic performance, and mechanistic attributes are analyzed comprehensively. By incorporating multifunctional supports or rational structural modifications, these systems deliver superior desulfurization efficiency, product selectivity, and recyclability. Despite such progress, commercial deployment is hindered by the following outstanding issues: long-term catalyst durability, continuous-flow reactor design, and full life-cycle cost optimization. Future research should, therefore, focus on elucidating structure–performance relationships, translating batch protocols into robust continuous processes, and performing rigorous environmental and techno-economic assessments to accelerate the industrial adoption of PTC-enabled desulfurization. Full article

Methyl groups can be obtained either from the diet (labile methyl groups) or produced endogenously (methylneogenesis) via one-carbon (C1-) metabolism as S-adenosylmethionine (SAM). The essential nutrients folate and choline (through betaine) are metabolically entwined to feed their methyl groups into C1-metabolism. A choline-deficient diet in rats produces a 31–40% reduction in liver folate content, 50% lower hepatic SAM levels, and a doubling of plasma homocysteine. Similarly, folate deficiency results in decreased total hepatic choline. Thus, sufficient intakes of both folate and choline (or betaine) contribute to safeguarding the methyl balance in the body. A significant amount of choline (as phosphatidylcholine) is produced in the liver via the SAM-dependent phosphatidylethanolamine methyltransferase. Experimental studies using diets deficient in several methyl donors have shown that supplemental betaine was able to rescue not only plasma betaine but also plasma folate. Fasting plasma homocysteine concentrations are mainly determined by folate intake or status, while the effect of choline or betaine on fasting plasma homocysteine is minor. This appears to contradict the finding that approximately 50% of cellular SAM is provided via the betaine-homocysteine methyltransferase (BHMT) pathway, which uses dietary choline (after oxidation to betaine) or betaine to convert homocysteine to methionine and then to SAM. However, it has been shown that the relative contribution of choline and betaine to cellular methylation is better reflected by measuring plasma homocysteine after a methionine load test. Choline or betaine supplementation significantly lowers post-methionine load homocysteine, whereas folate supplementation has a minor effect on post-methionine load homocysteine concentrations. This review highlights the interactions between folate and choline and the essentiality of choline as a key player in C1-metabolism. We further address some areas of interest for future work. Full article

Alzheimer’s dementia (AD) is a disease of the ageing brain. It begins in the hippocampal region with the epicentre in the entorhinal cortex, then gradually extends into adjacent brain areas involved in memory and cognition. The events which initiate the damage are unknown and under intense investigation. Localization to the hippocampus can now be explained by anatomical features of the blood vessels supplying this region. Blood supply and hence oxygen delivery to the area are jeopardized by poor flow through narrowed arteries. In genomic and metabolomic studies, the respiratory chain and mitochondrial pathways which generate ATP were leading pathways associated with AD. This review explores the notion that ATP depletion resulting from hippocampal hypoperfusion has a prime role in initiating damage. Sections cover sensing of ATP depletion and protective responses, vulnerable processes with very heavy ATP consumption (the malate shuttle, the glutamate/glutamine/GABA (γ-aminobutyric acid) cycle, and axonal transport), phospholipid disturbances and peroxidation by reactive oxygen species, hippocampal perfusion and the effects of hypertension, chronic hypoxia, and arterial vasospasm, and an overview of recent relevant genomic studies. The findings demonstrate strong scientific arguments for the proposal with increasing supportive evidence. These lines of enquiry should be pursued. Full article

The four-way shuttle storage and retrieval system (FWSS/RS) is an advanced automated warehousing solution for achieving green and intelligent logistics, and task allocation is crucial to its logistics efficiency. However, current research on task allocation in three-dimensional storage environments is mostly conducted in the single-operation mode that handles inbound or outbound tasks individually, with limited attention paid to the more prevalent composite operation mode where inbound and outbound tasks coexist. To bridge this gap, this study investigates the task allocation problem in an FWSS/RS under the composite operation mode, and deep reinforcement learning (DRL) is introduced to solve it. Initially, the FWSS/RS operational workflows and equipment motion characteristics are analyzed, and a task allocation model with the total task completion time as the optimization objective is established. Furthermore, the task allocation problem is transformed into a partially observable Markov decision process corresponding to reinforcement learning. Each shuttle is regarded as an independent agent that receives localized observations, including shuttle position information and task completion status, as inputs, and a deep neural network is employed to fit value functions to output action selections. Correspondingly, all agents are trained within an independent deep Q-network (IDQN) framework that facilitates collaborative learning through experience sharing while maintaining decentralized decision-making based on individual observations. Moreover, to validate the efficiency and effectiveness of the proposed model and method, experiments were conducted across various problem scales and transport resource configurations. The experimental results demonstrate that the DRL-based approach outperforms conventional task allocation methods, including the auction algorithm and the genetic algorithm. Specifically, the proposed IDQN-based method reduces the task completion time by up to 12.88% compared to the auction algorithm, and up to 8.64% compared to the genetic algorithm across multiple scenarios. Moreover, task-related factors are found to have a more significant impact on the optimization objectives of task allocation than transport resource-related factors. Full article

This study investigated the effects of a single-night sleep extension protocol on physical performance and cognitive function in physically active university students across different times of day. Using a within-subjects, counterbalanced crossover design, 24 physically active university students (17 males, 7 females; age: 22.7 ± 1.6 years) completed performance assessments under normal-sleep and sleep-extension conditions. Participants’ sleep was monitored via wrist actigraphy, and a comprehensive assessment battery comprising vertical jumps, Y-Balance tests, medicine-ball throws, 5 m shuttle-run tests, reaction-time tests, and digit-cancellation tests was administered at baseline (8 PM), morning (8 AM), and afternoon (4 PM). Sleep extension increased total sleep time by approximately 55 min (531.3 ± 56.8 min vs. 476.5 ± 64.2 min; p < 0.001, d = 0.91). Significant improvements were observed in 5 m shuttle-run performance at 8 AM (best distance: 102.8 ± 11.9 m vs. 93.3 ± 8.5 m, p < 0.001, d = 0.93; fatigue index: 13.1 ± 8.3% vs. 21.2 ± 9.5%, p < 0.001, d = 0.90), squat-jump heights (28.2 ± 8.0 cm vs. 26.3 ± 7.2 cm, p = 0.005, d = 0.25), simple reaction time (252.8 ± 55.3 ms vs. 296.4 ± 75.2 ms, p < 0.001, d = 0.66), and digit-cancellation performance (67.6 ± 12.6 vs. 63.0 ± 10.0 targets, p = 0.006, d = 0.40). Sleep extension significantly enhances both physical and cognitive performance in physically active individuals, with effects more pronounced during morning hours, partially attenuating typical circadian performance decline and establishing sleep extension as an effective, non-pharmacological strategy for optimizing performance capabilities. Full article

Large-conductance, voltage- and calcium-activated potassium (BK) channels are crucial regulators of cellular excitability, influenced by various signaling molecules, including heme. The BK channel contains a heme-sensitive motif located at the sequence ⁶¹²CKACH⁶¹⁶, which is a conserved heme regulatory motif (HRM) found in the cytochrome c protein family. This motif is situated within a linker region of approximately 120 residues that connect the RCK1 and RCK2 domains, and it also includes terminal α-helices similar to those found in cytochrome c family proteins. However, much of this region has yet to be structurally defined. We conducted a sequence alignment of the BK linker region with mitochondrial cytochrome c and cytochrome c domains from various hemoproteins to better understand this functionally significant region. In addition to the HRM motif, we discovered that important structural and functional elements of cytochrome c proteins are conserved in the BK RCK1-RCK2 linker. Firstly, the part of the BK region that is resolved in available atomic structures shows similarities in secondary structural elements with cytochrome c domain proteins. Secondly, the Met80 residue in cytochrome c domains, which acts as the second axial ligand to the heme iron, aligns with the BK channel. Beyond its role in electron shuttling, cytochrome c domains exhibit various catalytic properties, including peroxidase activity—specifically, the oxidation of suitable substrates using peroxides. Our findings reveal that the linker region endows human BK channels with peroxidase activity, showing an apparent H₂O₂ affinity approximately 40-fold greater than that of mitochondrial cytochrome c under baseline conditions. This peroxidase activity was reduced when substitutions were made at ⁶¹²CKACH⁶¹⁶ and other relevant sites. These results indicate that the BK channel possesses a novel module similar to the cytochrome c domains of hemoproteins, which may give rise to unique physiological functions for these widespread ion channels. Full article

Class IIa histone deacetylases (HDACs) are pleiotropic regulators of various differentiation pathways and adaptive responses. They form complexes with other co-repressors and can bind to DNA by interacting with selected transcription factors, with members of the Myocyte Enhancer Factor-2 (MEF2) family being the best characterized. A notable feature of class IIa HDACs is the substitution of tyrosine for histidine in the catalytic site, which has occurred over the course of evolution and has a profound effect on the efficiency of catalysis against acetyl-lysine. Another distinctive feature of this family of “pseudoenzymes” is the regulated nucleus–cytoplasm shuttling associated with several non-histone proteins that have been identified as potential substrates, including proteins localized in the cytosol. Within the complexity of class IIa HDACs, several aspects deserve further investigation. In the following, I will discuss some of the recent advances in our knowledge of class IIa HDACs. Full article

Background/Objectives: The bidirectional selection of the Roman low- (RLA) and Roman high-avoidance (RHA) rat strains for extremely slow vs. very rapid acquisition of the two-way (shuttle-box) avoidance response has generated two divergent phenotypic profiles: RHA rats exhibit a behavioural pattern and gene expression profile in the frontal cortex and hippocampus (HPC) that are relevant to social and attentional/cognitive schizophrenia-linked symptoms; on the other hand, RLA rats display phenotypic traits linked to increased anxiety and sensitivity to stress-induced depression-like behaviours. The present studies aimed to evaluate the enduring and potentially positive effects of neonatal handling-stimulation (NH) on the traits differentiating these two strains of rats. Methods: We evaluated the effects of NH on anxious behaviour, prepulse inhibition of startle (PPI), spatial working memory, and hormone responses to stress in adult rats of both strains. Furthermore, given the proposed involvement of neuronal/synaptic plasticity and neurotrophic factors in the development of anxiety, stress, depression, and schizophrenia-related symptoms, using Western blot (WB) we assessed the effects of NH on the content of brain-derived neurotrophic factor (BDNF), its trkB receptor and Polysialilated-Neural Cell Adhesion Molecule (PSA-NCAM), in the prefrontal cortex (PFC), anterior cingulate cortex (ACg), ventral (vHPC), and dorsal (dHPC) hippocampus of adult rats from both strains. Results: NH increased novelty-induced exploration and reduced anxiety, particularly in RLA rats, attenuated the stress-induced increment in corticosterone and prolactin plasma levels, and improved PPI and spatial working memory in RHA rats. These effects correlated to long-lasting increases of BDNF and PSA-NCAM content in PFC, ACg, and vHPC. Conclusions: Collectively, these findings show enduring and distinct NH effects on neuroendocrine and behavioural and cognitive processes in both rat strains, which may be linked to neuroplastic and synaptic changes in the frontal cortex and/or hippocampus. Full article

Dunaliella salina, a unicellular and eukaryotic alga, has been found to be one of the most salt-tolerant eukaryotes with a wide range of practical applications. To elucidate the underlying molecular mechanisms of D. salina in response to salinity stress, we performed transcriptome sequencing on samples under different stress conditions. A total of 82,333 unigenes were generated, 4720, 1111 and 2611 differentially expressed genes (DEGs) were identified under high salt stress, oxidative stress and hypertonic stress, respectively. Our analysis revealed that D. salina responds to salinity stress through a complex network of molecular mechanisms. Under high salt stress, starch degradation is regulated by AMY (α-amylase) and PYG (glycogen phosphorylase) with alternative expression patterns. This process is hypothesized to be initially constrained by low ATP levels due to impaired photosynthesis. The clustering analysis of DEGs indicated that starch and sucrose metabolism, as well as glycerol metabolism, are specifically reprogrammed under high salt stress. Glycerol metabolism, particularly involving GPDHs, plays a crucial role in maintaining osmotic balance under salinity stress. Key glycerol metabolism genes were up-regulated under salinity conditions, indicating the importance of this pathway in osmotic regulation. The G3P shuttle, involving mitochondrial GPDHs (c25199_g1 and c23777_g1), contributes to redox imbalance management under high salt, oxidative and hypertonic stresses. Notably, c23777_g1 is involved in the G3P shuttle under high salt, oxidative and hypertonic stresses, while c25199_g1 is specifically induced by hypertonic stress. The R2R3-MYB gene (c23845_g1) may respond to different effects of salinity stress by regulating the transcription of ROS-related genes. Our study provides a detailed understanding of the molecular responses of D. salina to salinity stress. We reveal the critical roles of starch and sucrose metabolism, glycerol metabolism and transcription factors in the D. salina adaptation to salinity. Full article

In Korea, the Public Health Center Mobile Healthcare Project was implemented in 2016. This project utilizes Information and Communication Technology (ICT) and big data to establish a health-related service foundation and a healthcare service operation system. Equipment and methods: This study recruited 1261 adolescents (660 males (13.40 ± 1.14 years, 156.12 ± 10.59 cm) and 601 females (13.51 ± 1.23 years, 154.45 ± 7.48 cm)) from 22 public health centers nationwide. Smart bands were provided, and the ‘Future Health’ application (APP) was installed on personal smartphones to assess body composition, physical fitness, and physical activity. Results: A paired sample t-test revealed height, 20 m shuttle run, grip strength, and long jump scores significantly differed after 24 weeks in males. Females exhibited significant height, 20 m shuttle run, grip strength, sit-ups, and long jump differences. Moderate physical activity (MPA, p < 0.001), vigorous physical activity (VPA, p < 0.001), and moderate-to-vigorous physical activity (MVPA, p < 0.001) were significantly different after 24 weeks in adolescents. These results establish that an ICT-based health promotion service can provide adolescent students with individual information from a centralized organization to monitor health behaviors and receive feedback regardless of location in South Korea. Full article

Oxidative stress overwhelms cellular antioxidant defenses, causing DNA damage and pro-tumorigenic signaling that accelerate cancer initiation and progression. Electron shuttles (ESs) from phytocompounds offer precise redox control but lack quantitative benchmarks. This study aims to give a clearer definition to electron shuttles by characterizing mulberry’s electrochemical capabilities via the three defined ES criteria and deciphering its mechanism against oxidative stress-related cancer. Using double-chambered microbial-fuel-cell power metrics, cyclic voltammetry, and compartmental fermentation modeling, we show that anthocyanin shows a significant difference (p < 0.05) in power density at ≥500 µg/mL (maximum of 2.06-fold power-density increase) and reversible redox cycling (ratio = 1.65), retaining >90% activity over four fermentation cycles. Molecular docking implicates meta-dihydroxyl motifs within the core scaffold in receptor binding, overturning the view that only ortho- and para-substituents participate in bioactivity. In vitro, anthocyanins both inhibit nitric oxide release and reduce DU-145 cell viability dose-dependently. Overall, our findings establish mulberry anthocyanins as robust electron shuttles with potential for integration into large-scale bio-electrochemical platforms and targeted redox-based cancer therapies. Full article

Films of functionalised multiwalled carbon nanotubes (MWCNTs) were fabricated as interlayers (interfacial layers between the cathode and separator) in a lithium–sulfur battery (LSB). Phenylsulfonate functionalisation of commercial MWCNTs was achieved via diazotisation to attach lithium phenylsulfonate groups and was characterised by IR and XPS spectroscopies. SEM-EDX showed sulfur and oxygen colocations due to the sulfonate groups on the interlayer surface. However, CHNS elemental microstudies showed a low degree of functionalisation. Without an interlayer, the LSB produced stable cycling at a capacity of 600 mA h g⁻¹_sulfur at 0.05 C for 40 cycles. Using an unfunctionalised interlayer as a control gave a capacity of 1400 mA h g⁻¹_sulfur for the first cycle but rapidly decayed to the same 600 mA h g⁻¹_sulfur at the 40th cycle at 0.05 C, suggesting a high degree of polysulfide shuttling. Adding a lithium phenylsulfonated interlayer gave an initial capacity increase to 1100 mA h g⁻¹_sulfur that lowered to 800 mA h g⁻¹_sulfur at 0.05 C by the 40th cycle, showing an increase in charge storage (33%) relative to the other cells. This performance increase has been attributed to lessened polysulfide shuttling due to repulsion by the phenylsulfonate groups, increased conductivity at the separator-cathode interface and an increase in surface area. Full article

The zinc finger protein with KRAB and SCAN domains 3 (ZKSCAN3) has emerged as a critical regulator of diverse cellular processes, including autophagy, cell cycle progression, and tumorigenesis. Structurally, ZKSCAN3 is characterized by its conserved DNA-binding zinc finger motifs, a SCAN domain mediating protein–protein interaction, and a KRAB repression domain implicated in transcriptional regulation. Post-translational modifications, such as phosphorylation and ubiquitination, dynamically modulate its subcellular localization and activity, enabling context-dependent functional plasticity. Functionally, ZKSCAN3 acts as a master switch in autophagy by repressing the transcription of autophagy-related genes under nutrient-replete conditions, while its nuclear-cytoplasmic shuttling under stress conditions links metabolic reprogramming to cellular survival. Emerging evidence also underscores its paradoxical roles in cancer: it suppresses tumor initiation by maintaining genomic stability yet promotes metastasis through epithelial–mesenchymal transition induction. Furthermore, epigenetic mechanisms, including promoter methylation and non-coding RNA regulation, fine-tune ZKSCAN3 expression, contributing to tissue-specific outcomes. Despite these insights, gaps remain in understanding the structural determinants governing its interaction with chromatin-remodeling complexes and the therapeutic potential of targeting ZKSCAN3 in diseases. Future investigations should prioritize integrating multi-omics approaches to unravel context-specific regulatory networks and explore small-molecule modulators for translational applications. This comprehensive analysis provides a framework for advancing our mechanistic understanding of ZKSCAN3 and its implications in human health and disease. This review synthesizes recent advances in elucidating the regulatory networks and functional complexity of ZKSCAN3, highlighting its dual roles in physiological and pathological contexts. Full article