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Background and Aims: Non‐alcoholic fatty liver disease (NAFLD) has been linked to type 2 diabetes (T2D), but also to hypothyroidism. Nevertheless, the relationship between thyroid function and NAFLD in diabetes is less clear. This study investigated associations between free thyroxine (fT4) or thyroid‐stimulating hormone (TSH) and NAFLD in recent‐onset diabetes. Methods: Participants with recent‐onset type 1 diabetes (T1D, n = 358), T2D (n = 596) or without diabetes (CON, n = 175) of the German Diabetes Study (GDS), a prospective longitudinal cohort study, underwent Botnia clamp tests and assessment of fT4, TSH, fatty liver index (FLI) and in a representative subcohort 1H‐magnetic resonance spectroscopy. Results: First, fT4 levels were similar between T1D and T2D (p =.55), but higher than in CON (T1D: p <.01; T2D: p <.001), while TSH concentrations were not different between all groups. Next, fT4 correlated negatively with FLI and positively with insulin sensitivity only in T2D (ß = −.110, p <.01; ß =.126, p <.05), specifically in males (ß = −.117, p <.05; ß =.162; p <.01) upon adjustments for age, sex and BMI. However, correlations between fT4 and FLI lost statistical significance after adjustment for insulin sensitivity (T2D: ß = −.021, p = 0.67; males with T2D: ß = −.033; p =.56). TSH was associated positively with FLI only in male T2D before (ß =.116, p <.05), but not after adjustments for age and BMI (ß =.052; p =.30). Conclusions: Steatosis risk correlates with lower thyroid function in T2D, which is mediated by insulin resistance and body mass, specifically in men, whereas no such relationship is present in T1D. [ABSTRACT FROM AUTHOR]

Background: The high prevalence of virulence-associated genes observed in isolates underscores the pathogenic potential of this bacterium. The presence of these genes confers enhanced survival, evasion of host defenses, and increased virulence. In this study, we investigate the presence and distribution of genes associated with virulence and assess the antimicrobial susceptibility patterns in clinical isolates of .Materials and method: This research focused on examining the 5ulti-drugs resistant (MDR) strains that were included in this investigation. The identification of these strains was validated using Oxa-51. The presence of the and genes was determined through conventional PCR techniques.Results: The results derived from Oxa-51 PCR confirmed the identification of all 50 selected strains of . Additionally, both the and genes were successfully identified in 82% of the MDR strains.Conclusion: Moreover, the varying antibiotic resistance patterns highlight the challenge in treating infections effectively. Strategies such as combination therapy, antimicrobial stewardship, and infection control measures should be considered to combat this multidrug-resistant pathogen.

Background: The ability of skeletal muscle to respond adequately to changes in nutrient availability, known as metabolic flexibility, is essential for the maintenance of metabolic health and loss of flexibility contributes to the development of diabetes and obesity. The tumour suppressor protein, p53, has been linked to the control of energy metabolism. We assessed its role in the acute control of nutrient allocation in skeletal muscle in the context of limited nutrient availability., Methods: A mouse model with inducible deletion of the p53-encoding gene, Trp53, in skeletal muscle was generated using the Cre-loxP-system. A detailed analysis of nutrient metabolism in mice with control and knockout genotypes was performed under ad libitum fed and fasting conditions and in exercised mice., Results: Acute deletion of p53 in myofibres of mice activated catabolic nutrient usage pathways even under ad libitum fed conditions, resulting in significantly increased overall energy expenditure (+10.6%; P = 0.0385) and a severe nutrient deficit in muscle characterized by depleted intramuscular glucose and glycogen levels (-62,0%; P < 0.0001 and -52.7%; P < 0.0001, respectively). This was accompanied by changes in marker gene expression patterns of circadian rhythmicity and hyperactivity (+57.4%; P = 0.0068). These metabolic changes occurred acutely, within 2-3 days after deletion of Trp53 was initiated, suggesting a rapid adaptive response to loss of p53, which resulted in a transient increase in lactate release to the circulation (+46.6%; P = 0.0115) from non-exercised muscle as a result of elevated carbohydrate mobilization. Conversely, an impairment of proteostasis and amino acid metabolism was observed in knockout mice during fasting. During endurance exercise testing, mice with acute, muscle-specific Trp53 inactivation displayed an early exhaustion phenotype with a premature shift in fuel usage and reductions in multiple performance parameters, including a significantly reduced running time and distance (-13.8%; P = 0.049 and -22.2%; P = 0.0384, respectively)., Conclusions: These findings suggest that efficient nutrient conservation is a key element of normal metabolic homeostasis that is sustained by p53. The homeostatic state in metabolic tissues is actively maintained to coordinate efficient energy conservation and metabolic flexibility towards nutrient stress. The acute deletion of Trp53 unlocks mechanisms that suppress the activity of nutrient catabolic pathways, causing substantial loss of intramuscular energy stores, which contributes to a fasting-like state in muscle tissue. Altogether, these findings uncover a novel function of p53 in the short-term regulation of nutrient metabolism in skeletal muscle and show that p53 serves to maintain metabolic homeostasis and efficient energy conservation., (© 2024 The Author(s). Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Background and Purpose: Remote ischaemic preconditioning (rIPC) for cardioprotection is severely impaired in diabetes, and therapeutic options to restore it are lacking. The vascular endothelium plays a key role in rIPC. Given that the activity of endothelial nitric oxide synthase (eNOS) is inhibited by proline-rich tyrosine kinase 2 (Pyk2), we hypothesized that pharmacological Pyk2 inhibition could restore eNOS activity and thus restore remote cardioprotection in diabetes., Experimental Approach: New Zealand obese (NZO) mice that demonstrated key features of diabetes were studied. The consequence of Pyk2 inhibition on endothelial function, rIPC and infarct size after myocardial infarction were evaluated. The impact of plasma from mice and humans with or without diabetes was assessed in isolated buffer perfused murine hearts and aortic rings., Key Results: Plasma from nondiabetic mice and humans, both subjected to rIPC, caused remote tissue protection. Similar to diabetic humans, NZO mice demonstrated endothelial dysfunction. NZO mice had reduced circulating nitrite levels, elevated arterial blood pressure and a larger infarct size after ischaemia and reperfusion than BL6 mice. Pyk2 increased the phosphorylation of eNOS at its inhibitory site (Tyr656), limiting its activity in diabetes. The cardioprotective effects of rIPC were abolished in diabetic NZO mice. Pharmacological Pyk2 inhibition restored endothelial function and rescued cardioprotective effects of rIPC., Conclusion and Implications: Endothelial function and remote tissue protection are impaired in diabetes. Pyk2 is a novel target for treating endothelial dysfunction and restoring cardioprotection through rIPC in diabetes., (© 2024 The Author(s). British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

The Rab-GTPase-activating protein (RabGAP) TBC1D4 (AS160) represents a key component in the regulation of glucose transport into skeletal muscle and white adipose tissue (WAT) and is therefore crucial during the development of insulin resistance and type 2 diabetes. Increased daily activity has been shown to be associated with improved postprandial hyperglycemia in allele carriers of a loss-of-function variant in the human TBC1D4 gene. Using conventional Tbc1d4-deficient mice (D4KO) fed a high-fat diet, we show that moderate endurance exercise training leads to substantially improved glucose and insulin tolerance and enhanced expression levels of markers for mitochondrial activity and browning in WAT from D4KO animals. Importantly, in vivo and ex vivo analyses of glucose uptake revealed increased glucose clearance in interscapular brown adipose tissue and WAT from trained D4KO mice. Thus, chronic exercise is able to overcome the genetically induced insulin resistance caused by Tbc1d4 depletion. Gene variants in TBC1D4 may be relevant in future precision medicine as determinants of exercise response., (© 2024 by the American Diabetes Association.)

This study presents the phase analysis, microstructural characteristics, and mechanical property evaluation of the as-cast and quenched Ti-15Mo-xFe alloys with high iron content ranging from 4 to 12 weight percent. All the four alloys were produced in a vacuum-arc melting furnace. Heat treatment in the form of solution treatment was performed in a muffle furnace at a temperature of 1100 °C, with 1-h holding time and the samples were rapidly quenched in ice-brine. X-ray diffractometer (XRD) was used to analyses the phases present in each alloy whereas the optical microscope (OM) was employed to track the microstructural evolution and percentage porosity. The mechanical properties of the alloys were evaluated using a tensile test and compression test method while the micro-Vickers hardness measurements were conducted to evaluate hardness of the alloys. The XRD patterns of as-cast showed peaks belonging to the β and α″ phases and intermetallic B2 TiFe phases. The as quenched XRD peaks illustrated β phase only and Fe·Ti·O 2 phases. The as-cast OM micrographs revealed equiaxed β grains, substructures, dendritic structure, and pores forming around the grain boundaries. The quenched OM showed only β equiaxed grains with pores throughout the grain boundaries. The tensile properties such as ultimate tensile strength (UTS) and elastic modulus (E) of as-cast TMF0 were 264 MPa and 79 GPa respectively and these properties changed upon quenching to 411 MPa and 66 GPa respectively. The elastic modulus of TMF1 in as-cast condition was 74 GPa. The UTS and E of TMF1, TMF2, and TMF3 in as-cast and quenched conditions were not recorded due to the fragility of the samples that failed prior to yielding any useful data. The compressive strength in as-cast and in quenched condition decreased with an increase in Fe content. The micro-Vickers hardness in as-cast and quenched conditions showed a similar trend with hardness increasing slightly upon quenching for TMF0, TMF1, and TMF3 alloys but slightly decreased in the case of TMF2. The fracture surfaces of all the as-cast and quenched alloys were comprised of ductile and brittle fracture., (© 2024. The Author(s).)

Purpose: To identify frequently studied significant preoperative risk factors for meniscal allograft transplantation (MAT) failure., Methods: Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines were used to conduct this systematic review. The database analysis was performed in May 2022 and included PubMed, Embrace, and Cochrane. Studies between January 1, 2000, and January 1, 2021, were reviewed with search terms, including "meniscal," "meniscus," "transplantation," "transplant," and "allograft." Twenty-one full-text manuscripts met inclusion criteria of studies assessing preoperative risk factors for MAT failure defined as either clinical failure (Lysholm <65) or surgical failure (revision, removal, or conversion to knee arthroplasty)., Results: In total, 21 studies were included, comprising 47.6% with Level of Evidence III and 52.4% with Level of Evidence IV. The analysis involved 2,533 patients, and the mean final follow-up ranged from 2.2 to 20.0 years. The presence of high-grade cartilage defects was the only factor found predictive of MAT surgical failure in the majority of studies in which it was analyzed (5/7 studies, 71.4%). Four of the 5 studies that found high-grade cartilage defects to be a predictor of MAT surgical failure did not treat all cartilage lesions, whereas the 2 studies that found high-grade cartilage defects an insignificant predictor of MAT surgical failure treated all defects at the time of MAT. For clinical failure, no risk factors were predictive of MAT failure in the majority of studies, although smoking and concomitant ligamentous or realignment procedures were significant in 1 study., Conclusions: The presence of untreated high-grade cartilage appears to elevate the risk of surgical MAT failure; however, concomitant treatment of defects may mitigate their detrimental effect. There is no clear risk factor that consistently predicts clinical failure. Age, sex, body mass index, knee compartment, time from prior meniscectomy, femorotibial alignment (after correction), concomitant cartilage procedure, and laterality do not routinely influence MAT failure., Level of Evidence: Level IV, systematic review of Level III and IV studies., Competing Interests: Disclosures The authors report no conflicts of interest in the authorship and publication of this article. Full ICMJE author disclosure forms are available for this article online, as supplementary material., (Copyright © 2023 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Obesity is one of the diseases with severe health consequences and rapidly increasing worldwide prevalence. Understanding the complex network of food intake and energy balance regulation is an essential prerequisite for pharmacological intervention with obesity. G protein-coupled receptors (GPCRs) are among the main modulators of metabolism and energy balance. They, for instance, regulate appetite and satiety in certain hypothalamic neurons, as well as glucose and lipid metabolism and hormone secretion from adipocytes. Mutations in some GPCRs, such as the melanocortin receptor type 4 (MC4R), have been associated with early-onset obesity. Here, we identified the adhesion GPCR latrophilin 1 (ADGRL1/LPHN1) as a member of the regulating network governing food intake and the maintenance of energy balance. Deficiency of the highly conserved receptor in mice results in increased food consumption and severe obesity, accompanied by dysregulation of glucose homeostasis. Consistently, we identified a partially inactivating mutation in human ADGRL1/LPHN1 in a patient suffering from obesity. Therefore, we propose that LPHN1 dysfunction is a risk factor for obesity development., (© 2024. The Author(s).)

This paper illustrates a novel and cost-effective wireless monitoring system specifically developed for operational modal analysis of bridges. The system employs battery-powered wireless sensors based on MEMS accelerometers that dynamically balance power consumption with high processing features and a low-power, low-cost Wi-Fi module that ensures operation for at least five years. The paper focuses on the system's characteristics, stressing the challenges of wireless communication, such as data preprocessing, synchronization, system lifetime, and simple configurability, achieved through the integration of a user-friendly, web-based graphical user interface. The system's performance is validated by a lateral excitation test of a model structure, employing dynamic identification techniques, further verified through FEM modeling. Later, a system composed of 30 sensors was installed on a concrete arch bridge for continuous OMA to assess its behavior. Furthermore, emphasizing its versatility and effectiveness, displacement is estimated by employing conventional and an alternative strategy based on the Kalman filter.

Chronic stress episodes increase metabolic disease risk even after recovery. We propose that persistent stress detrimentally impacts hepatic metabolic reprogramming, particularly mitochondrial function. In male C57BL/6 mice chronic variable stress (Cvs) reduced energy expenditure (EE) and body mass despite increased energy intake versus controls. This coincided with decreased glucose metabolism and increased lipid β-oxidation, correlating with EE. After Cvs, mitochondrial function revealed increased thermodynamic efficiency (ƞ-opt) of complex CI, positively correlating with blood glucose and NEFA and inversely with EE. After Cvs recovery, the metabolic flexibility of hepatocytes was lost. Reduced CI-driving NAD + /NADH ratio, and diminished methylation-related one-carbon cycle components hinted at epigenetic regulation. Although initial DNA methylation differences were minimal after Cvs, they diverged during the recovery phase. Here, the altered enrichment of mitochondrial DNA methylation and linked transcriptional networks were observed. In conclusion, Cvs rapidly initiates the reprogramming of hepatic energy metabolism, supported by lasting epigenetic modifications., Competing Interests: The authors declare no competing interest., (© 2024 The Authors.)

Impaired skeletal muscle glucose uptake is a key feature in the development of insulin resistance and type 2 diabetes. Skeletal muscle glucose uptake can be enhanced by a variety of different stimuli, including insulin and contraction as the most prominent. In contrast to the clearance of glucose from the bloodstream in response to insulin stimulation, exercise-induced glucose uptake into skeletal muscle is unaffected during the progression of insulin resistance, placing physical activity at the center of prevention and treatment of metabolic diseases. The two Rab GTPase-activating proteins (RabGAPs), TBC1D1 and TBC1D4, represent critical nodes at the convergence of insulin- and exercise-stimulated signaling pathways, as phosphorylation of the two closely related signaling factors leads to enhanced translocation of glucose transporter 4 (GLUT4) to the plasma membrane, resulting in increased cellular glucose uptake. However, the full network of intracellular signaling pathways that control exercise-induced glucose uptake and that overlap with the insulin-stimulated pathway upstream of the RabGAPs is not fully understood. In this review, we discuss the current state of knowledge on exercise- and insulin-regulated kinases as well as hypoxia as stimulus that may be involved in the regulation of skeletal muscle glucose uptake.

Recently, we have shown that after partial hepatectomy (PHx), an increased hepatic blood flow initiates liver growth in mice by vasodilation and mechanically-triggered release of angiocrine signals. Here, we use mass spectrometry to identify a mechanically-induced angiocrine signal in human hepatic endothelial cells, that is, myeloid-derived growth factor (MYDGF). We show that it induces proliferation and promotes survival of primary human hepatocytes derived from different donors in two-dimensional cell culture, via activation of mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 3 (STAT3). MYDGF also enhances proliferation of human hepatocytes in three-dimensional organoids. In vivo, genetic deletion of MYDGF decreases hepatocyte proliferation in the regenerating mouse liver after PHx; conversely, adeno-associated viral delivery of MYDGF increases hepatocyte proliferation and MAPK signaling after PHx. We conclude that MYDGF represents a mechanically-induced angiocrine signal and that it triggers growth of, and provides protection to, primary mouse and human hepatocytes., (© 2024. The Author(s).)

MnPt's exceptional stability and extremely high Néel temperature have generated a lot of interest in data storage applications. Previously, it was reported experimentally that the MnPt alloy shows ferromagnetic (FM) behavior at room temperature. In this study, the effects of partial substitution of Pt with Pd, Au, and Ag on magnetic properties is investigated using density functional theory. The stability of Mn 50 Pt 50-x M x (M = Pd, Au, Ag, x = 6.25, 12.5, 18.75) alloys was assessed by determining their thermodynamic, magnetic, and mechanical properties. The calculated lattice constants of Mn 50 Pt 50 agree well with available theoretical results. The Mn 50 Pt 50-x M x alloys' formability was assessed by measuring the thermodynamic stability using the heat of formation. It was found that B2 Mn 50 Pt 50-x Pd x alloys (0 ≤ x ≤ 18.75) are thermodynamically stable due to the negative heat of formation close to that of a pristine MnPt alloy. Based on the elasticity results, the B2 Mn 50 Pt 50-x Pd x is most likely to undergo martensitic transformation for the entire considered composition range. From the calculated values of the Poisson's ratio, it is shown that an increase in Pd, Ag, and Au effectively improves the ductility of the B2 Mn 50 Pt 50-x M x compounds. It was revealed that ferromagnetism is maintained with Pd addition but significantly reduced in the case of Au and Ag. Thus, this work showed that density functional theory can be exploited to propose new possible compositions for future magnets in spintronic applications.

Aims: Exercise training induces white adipose tissue (WAT) beiging and improves glucose homeostasis and mitochondrial function in rodents. This could be relevant for type 2 diabetes in humans, but the effect of physical fitness on beiging of subcutaneous WAT (scWAT) remains unclear. This translational study investigates if beiging of scWAT associates with physical fitness in healthy humans and recent-onset type 2 diabetes and if a voluntary running wheel intervention is sufficient to induce beiging in mice., Materials and Methods: Gene expression levels of established beiging markers were measured in scWAT biopsies of humans with (n = 28) or without type 2 diabetes (n = 28), stratified by spiroergometry into low (L-FIT; n = 14 each) and high physical fitness (H-FIT; n = 14 each). High-fat diet-fed FVB/N mice underwent voluntary wheel running, treadmill training or no training (n = 8 each group). Following the training intervention, mitochondrial respiration and content of scWAT were assessed by high-resolution respirometry and citrate synthase activity, respectively., Results: Secreted CD137 antigen (Tnfrsf9/Cd137) expression was three-fold higher in glucose-tolerant H-FIT than in L-FIT, but not different between H-FIT and L-FIT with type 2 diabetes. In mice, both training modalities increased Cd137 expression and enhanced mitochondrial content without changing respiration in scWAT. Treadmill but not voluntary wheel running led to improved whole-body insulin sensitivity., Conclusions: Higher physical fitness and different exercise interventions associated with higher gene expression levels of the beiging marker CD137 in healthy humans and mice on a high-fat diet. Humans with recent-onset type 2 diabetes show an impaired adipose tissue-specific response to physical activity., (© 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)