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The crustal structure of Mercury's large impact basins provides valuable insights into the planet's geological history. For a warm crust, a post‐impact basin structure will viscously relax with inward flow of crustal materials toward the basin center. This effect drastically diminishes the crustal thickness contrasts and associated Bouguer gravity contrasts between the basin center and its surroundings. Here, we analyze Bouguer contrasts of 36 basins (diameter > ${ >} $300 km) located in the northern hemisphere as a proxy for viscoelastic relaxation. Thermal evolution models, assuming the present 3:2 spin‐orbit configuration, are used to predict crustal temperatures. Our analysis reveals that the expected correlation between zones of warm crust and low Bouguer contrast from relaxation is not observed in the available data. This suggests that crustal temperatures have changed in the past, potentially due to a change in Mercury's orbit or to a major volcanic event associated with smooth plain formation. Plain Language Summary: Mercury's impact basins and their crustal structure provide important clues about the planet's geological past and present‐day state. We study Mercury's crust at large impact basins by using information from gravity measurements and temperature estimates from thermal evolution models that consider the surface temperature pattern caused by Mercury's present‐day orbit. In regions with warm interior, the crustal structure of large basins is expected to relax more readily compared to colder regions. Here, we examine 36 large basins (diameter > ${ >} $300 km) in the northern hemisphere, where the gravity data is well resolved, to investigate this process. Our results show no correlation between gravity data at basins' location, modeled local temperature, and expected impact basin relaxation. This suggests that crustal temperatures have changed in the past, potentially due to a change in Mercury's orbit or to a major volcanic event associated with smooth plain formation. Key Points: Observed Bouguer anomaly contrasts and predicted crustal temperatures are used to investigate viscoelastic relaxation of Mercury's basinsOur findings do not indicate the anticipated pattern where basins exhibiting greater relaxation are situated in areas with hotter crustCrustal temperatures varied over time, likely due to rotation state changes or major volcanic events linked to smooth plain formation [ABSTRACT FROM AUTHOR]

Sustained androgen receptor (AR) signaling during relapse is a central driver of metastatic castration-resistant prostate cancer (mCRPC). Current AR antagonists, such as enzalutamide, fail to provide long-term benefit for the mCRPC patients who have dramatic increases in AR expression. Here, we report AR antagonists with efficacy in AR-overexpressing models. These molecules bind to the ligand-binding domain of the AR, promote AR localization to the nucleus, yet potently and selectively down-regulate AR-target genes. The molecules BG-15a and the pharmacokinetically optimized BG-15n elicit a decrease in cell and tumor growth in vitro and in vivo in models of mCRPC. BG-15a/n treatment causes the collapse of chromatin loops between enhancers and promoters at key genes in the AR-driven epigenome. AR binding in the promoter, as well as 3D chromatin clustering, is needed for genes to respond. BG-15a/n represent promising agents for treating patients with relapsed AR-driven mCRPC tumors. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a kind of neurodegenerative diseases characterized by beta-amyloid deposition and neurofibrillary tangles and is also the main cause of dementia. According to statistics, the incidence of AD is constantly increasing, bringing a great burden to individuals and society. Nonetheless, there is no cure for AD, and the available drugs are very limited apart from cholinesterase inhibitors and N-Methyl-D-aspartic acid (NMDA) antagonists, which merely alleviate symptoms without delaying the progression of the disease. Therefore, there is an urgent need to develop a medicine that can delay the progression of AD or cure it. In recent years, increasing evidence suggests that metal complexes have the enormous potential to treat AD through inhibiting the aggregation and cytotoxicity of A β , interfering with the congregation and hyperphosphorylation of tau, regulating dysfunctional synaptic and unbalanced neurotransmitters, etc. In this review, we summarize the current metal complexes and their mechanisms of action for treating AD, including ruthenium, platinum, zinc, vanadium, copper, magnesium, and other complexes. [ABSTRACT FROM AUTHOR]

Background: Hypertension is a major cause of mortality worldwide. The kidneys play a crucial role in regulating blood pressure and fluid volume. The relationship between the kidneys and hypertension is complex, involving factors such as the renin–angiotensin system, oxidative stress, and inflammation. This study aims to assess the levels of inflammatory markers, oxidative stress, and metabolic factors in the kidneys, focusing on their potential role in early renal damage and their association with the development of hypertension. Methods: This study was designed to compare the levels of selected inflammatory markers, e.g., interleukins, tumor necrosis factor-α (TNF-α), transforming growth factor, and serine/threonine-protein (mTOR); oxidative stress markers such as malondialdehyde, sulfhydryl group, and glucose (GLC); and metabolic markers among other enzymes, such as alanine transaminase (ALT), aspartate transaminase (AST), hexokinase II (HK-II), and hypoxia-inducible factor-1α (HIF-1α), as well as creatinine in the kidneys of spontaneously hypertensive rats (SHR/NCrl, n = 12) and Wistar Kyoto rats (WKY/NCrl, n = 12). Both juvenile (5 weeks old) and maturing (10 weeks old) specimens were examined using spectrophotometric methods, e.g., ELISA. Results: Juvenile SHRs exhibited reduced renal levels of all studied cytokines and chemokines, with lower oxidative stress and deficits in the mTOR and HK-II levels compared to the age-matched WKYs. Maturing SHRs showed increased renal levels of interleukin-1β (IL-1β), IL-6, IL-18, and TNF-α, alongside elevated carbonyl stress and increased HIF-1α as opposed to their control peers. The levels of all other studied markers were normalized in these animals, except for ALT (increased), ALP, and GLC (both reduced). Conclusions: This study underscores the significant impact of inflammatory, oxidative stress, and metabolic marker changes on renal function. Juvenile SHRs display lower marker levels, indicating an immature immune response and potential subclinical kidney damage that may contribute to hypertension development. In contrast, mature SHRs exhibit chronic inflammation, oxidative dysregulation, and metabolic disturbances, suggesting cellular damage. These changes create a feedback loop that worsens kidney function and accelerates hypertension progression, highlighting the kidneys' crucial role in both initiating and exacerbating this condition. [ABSTRACT FROM AUTHOR]

Radiative transfer models of vegetation play a crucial role in the development of remote sensing methods by providing a theoretical framework to explain how electromagnetic radiation interacts with vegetation in different spectral regions. A limiting factor in model development has been the lack of sufficiently detailed ground reference data on both the structural and spectral characteristics of forests needed for testing and validating the models. In this data description paper, we present a dataset on the structural and spectral properties of 58 stands in temperate, hemiboreal, and boreal European forests. It is specifically designed for the development and validation of radiative transfer models for forests but can also be utilized in other remote sensing studies. It comprises detailed data on forest structure based on forest inventory measurements, terrestrial and airborne laser scanning, and digital hemispherical photography. Furthermore, the data include spectral properties of the same forests at multiple scales: reflectance spectra of tree leaves and needles (based on laboratory measurements), the forest floor (based on in situ measurements), and entire stands (based on airborne measurements), as well as transmittance spectra of tree leaves and needles and entire tree canopies (based on laboratory and in situ measurements, respectively). We anticipate that these data will have wide use in testing and validating radiative transfer models for forests and in the development of remote sensing methods for vegetation. The data can be accessed at Hovi et al. (2024a, 10.23729/9a8d90cd-73e2-438d-9230-94e10e61adc9) (for laboratory and field data) and Hovi et al. (2024b, 10.23729/c6da63dd-f527-4ec9-8401-57c14f77d19f) (for airborne data). [ABSTRACT FROM AUTHOR]

To investigate how clinicians correct patient misconceptions, we analyzed 23 video recordings of primary care visits. Analysis focused on operationalizing, identifying, and characterizing clinician corrections, integrating two inductive approaches: microanalysis of clinical interaction and conversation analysis. According to our definition, patient misconception-clinician correction episodes met three essential criteria: (1) the clinician refuted something the patient had said, (2) which the patient had presented without uncertainty, and (3) which contained a proposition that was factually incorrect. We identified 59 such episodes; the patient misconceptions most commonly related to medication issues; fewer than half had foreseeable implications for patients' future actions. We identified seven clinician correction practices: Three direct practices (displaying surprise, marking disagreement, contradicting the patient) and four indirect practices (presenting the correct proposition, providing explanations, invoking an outside authority, demonstrating with evidence). We found an almost equal distribution of these direct and indirect practices. [ABSTRACT FROM AUTHOR]

Pine wilt disease, caused by the pine wood nematode (Bursaphelenchus xylophilus), poses a serious threat to forests in Korea. In this study, we investigated the resistance of Pinus densiflora to B. xylophilus following treatment with a fungal elicitor derived from Penicillium chrysogenum through trunk injection and soil drenching. Soil drenching with the fungal elicitor led to increased accumulation of two key defensive compounds: pinosylvin monomethyl ether (PME) and dihydropinosylvin monomethyl ether (DPME) in the needles. In untreated control plants inoculated with B. xylophilus, 67.9% died within five months, whereas only 33.3% of plants pretreated with the elicitor succumbed. Trunk injection of the fungal elicitor also significantly enhanced PME production. The PME concentration in the needles peaked at 155.4 µg/g dry weight (DW) four weeks post-elicitor injection. To assess the impact of elicitor treatment on nematode resistance, we monitored the downward movement of B. xylophilus in plants two months post-injection of fungal elicitor. Nematodes were introduced at the upper internodal segments of branches, and their mobility to the lower segments was measured. In elicitor-treated trees, the movement and population of B. xylophilus were significantly reduced, highlighting the effectiveness of the treatment. These results demonstrate that fungal elicitor treatments, through soil drenching or trunk injection, can enhance the resistance of P. densiflora to B. xylophilus. This eco-friendly approach offers a promising strategy for managing pine wilt disease in susceptible pine species. [ABSTRACT FROM AUTHOR]

Recent studies have suggested that injection of solid particles such as alumina and calcite particles for stratospheric aerosol injection (SAI) instead of sulfur-based injections could reduce some of the adverse side effects of SAI such as ozone depletion and stratospheric heating. Here, we present a version of the global aerosol–chemistry–climate model SOCOL-AERv2 and the Earth system model (ESM) SOCOLv4 which incorporate a solid-particle microphysics scheme for assessment of SAI of solid particles. Microphysical interactions of the solid particle with the stratospheric sulfur cycle were interactively coupled to the heterogeneous chemistry scheme and the radiative transfer code (RTC) for the first time within an ESM. Therefore, the model allows simulation of heterogeneous chemistry at the particle surface as well as feedbacks between microphysics, chemistry, radiation and climate. We show that sulfur-based SAI results in a doubling of the stratospheric aerosol burden compared to the same mass injection rate of calcite and alumina particles with a radius of 240 nm. Most of the sulfuric acid aerosol mass resulting from SO2 injection does not need to be lifted to the stratosphere but is formed after in situ oxidation and subsequent water uptake in the stratosphere. Therefore, to achieve the same radiative forcing, larger injection rates are needed for calcite and alumina particle injection than for sulfur-based SAI. The stratospheric sulfur cycle would be significantly perturbed, with a reduction in stratospheric sulfuric acid burden by 53 %, when injecting 5 Mtyr-1 (megatons per year) of alumina or calcite particles of 240 nm radius. We show that alumina particles will acquire a sulfuric acid coating equivalent to about 10 nm thickness if the sulfuric acid is equally distributed over the whole available particle surface area in the lower stratosphere. However, due to the steep contact angle of sulfuric acid on alumina particles, the sulfuric acid coating would likely not cover the entire alumina surface, which would result in available surface for heterogeneous reactions other than the ones on sulfuric acid. When applying realistic uptake coefficients of 1.0, 10-5 and 10-4 for H2SO4 , HCl and HNO3 , respectively, the same scenario with injections of calcite particles results in 94 % of the particle mass remaining in the form of CaCO3. This likely keeps the optical properties of the calcite particles intact but could significantly alter the heterogeneous reactions occurring on the particle surfaces. The major process uncertainties of solid-particle SAI are (1) the solid-particle microphysics in the injection plume and degree of agglomeration of solid particles on the sub-ESM grid scale, (2) the scattering properties of the resulting agglomerates, (3) heterogeneous chemistry on the particle surface, and (4) aerosol–cloud interactions. These uncertainties can only be addressed with extensive, coordinated experimental and modelling research efforts. The model presented in this work offers a useful tool for sensitivity studies and incorporating new experimental results on SAI of solid particles. [ABSTRACT FROM AUTHOR]

Background and Aims: As a biomarker of insulin resistance (IR) in patients with acute myocardial infarction (AMI), the triglyceride‐glucose index (TyG index) has received significant attention. However, most research on AMI has focused on male patients, as it is traditionally believed to primarily affect males. Therefore, this study was conducted on a female population with AMI to investigate the potential correlation between the TyG index and their outcomes. Methods: A total of 320 women who were admitted to Fujian Provincial Hospital for AMI between January 2017 and December 2019 were included in this study. The TyG index was calculated using the following formula: ln [fasting triglycerides (TG) (mg/dL) × fasting plasma glucose (FPG) (mg/dL)/2]. The primary endpoint of the study was the occurrence of major adverse cardiovascular and cerebrovascular events (MACCEs), which included all‐cause mortality, myocardial infarction, repeat revascularization, rehospitalization for heart failure and stroke. The association between the TyG index and unfavorable outcomes in female patients was investigated using the Cox proportional hazards regression model. Results: It was ultimately estimated that 111 patients developed MACCEs. Females with high TyG indices had a higher prevalence of diabetes, elevated heart rates, and hemoglobin A1c, as well as a higher likelihood of undergoing thrombus aspiration and stent placement. The TyG index was found to be positively correlated with the prevalence of hypertension, diabetes, low‐density lipoprotein cholesterol, hemoglobin A1c, and damaged vessels. However, this correlation was modest, yet statistically significant. Furthermore, after adjusting for conventional risk factors, the TyG index (HR: 4.292, 95% CI: 2.784–6.616, p < 0.001) was independently associated with MACCEs. Conclusion: As an independent risk predictor, the TyG index has the potential to enhance clinical outcomes for women with AMI. [ABSTRACT FROM AUTHOR]

This narrative review examines the relationship between dopamine-related genetic polymorphisms, personality traits, and athletic success. Advances in sports genetics have identified specific single nucleotide polymorphisms (SNPs) in dopamine-related genes linked to personality traits crucial for athletic performance, such as motivation, cognitive function, and emotional resilience. This review clarifies how genetic variations can influence athletic predisposition through dopaminergic pathways and environmental interactions. Key findings reveal associations between specific SNPs and enhanced performance in various sports. For example, polymorphisms such as COMT Val158Met rs4680 and BDNF Val66Met rs6265 are associated with traits that could benefit performance, such as increased focus, stress resilience and conscientiousness, especially in martial arts. DRD3 rs167771 is associated with higher agreeableness, benefiting teamwork in sports like football. This synthesis underscores the multidimensional role of genetics in shaping athletic ability and advocates for integrating genetic profiling into personalized training to optimize performance and well-being. However, research gaps remain, including the need for standardized training protocols and exploring gene–environment interactions in diverse populations. Future studies should focus on how genetic and epigenetic factors can inform tailored interventions to enhance both physical and psychological aspects of athletic performance. By bridging genetics, personality psychology, and exercise science, this review paves the way for innovative training and performance optimization strategies. [ABSTRACT FROM AUTHOR]

Opioid-seeking behaviors depend on glutamatergic plasticity in the nucleus accumbens core (NAcc). Here we investigated whether the behavioral and synaptic effects of opioids are influenced by acid-sensing ion channel 1A (ASIC1A). We tested the effects of ASIC1A on responses to several opioids and found that Asic1a−/− mice had elevated behavioral responses to acute opioid administration as well as opioid seeking behavior in conditioned place preference (CPP). Region-restricted restoration of ASIC1A in NAcc was sufficient to reduce opioid CPP, suggesting NAcc is an important site of action. We next tested the effects of oxycodone withdrawal on dendritic spines in NAcc. We found effects of oxycodone and ASIC1A that contrasted with changes previously described following cocaine withdrawal. Finally, we examined α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated and N-methyl-D-aspartic acid (NMDA) receptor-mediated synaptic currents in NAcc. Oxycodone withdrawal, like morphine withdrawal, increased the AMPAR/NMDAR ratio in Asic1a+/+ mice, whereas oxycodone withdrawal reduced the AMPAR/NMDAR ratio in Asic1a−/− mice. A single dose of oxycodone was sufficient to induce this paradoxical effect in Asic1a−/− mice, suggesting an increased sensitivity to oxycodone. We conclude that ASIC1A plays an important role in the behavioral and synaptic effects of opioids and may constitute a potential future target for developing novel therapies. [ABSTRACT FROM AUTHOR]

Background: Inflammation is characterized by a metabolic switch promoting glycolysis and lactate production. Hexokinases (HK) catalyze the first reaction of glycolysis and inhibition of epithelial HK2 protected from colitis in mice. HK2 expression has been described as elevated in patients with intestinal inflammation; however, there is conflicting data from few cohorts especially with severely inflamed individuals; thus, systematic studies linking disease activity with HK2 levels are needed. Methods: We examined the relationship between HK2 expression and inflammation severity using bulk transcriptome data derived from the mucosa of thoroughly phenotyped inflammatory bowel disease (IBD) patients of two independent cohorts including both subtypes Crohn's disease (CD) and ulcerative colitis (UC). Publicly available single-cell RNA sequencing data were analyzed, and immunofluorescence staining on colonic biopsies of unrelated patients with intestinal inflammation was performed to confirm the RNA-based findings on cellular and protein level. Results: HK2 expression gradually increased from mild to intermediate inflammation, yet strongly declined at high inflammation scores. Expression of epithelial marker genes also declined at high inflammation scores, whereas that of candidate immune marker genes increased, indicating a cellular remodeling of the mucosa during inflammation with an infiltration of HK2-negative immune cells and a loss of terminal differentiated epithelial cells in the apical epithelium—the main site of HK2 expression. Normalizing for the enterocyte loss clearly identified epithelial HK2 expression as gradually increasing with disease activity and remaining elevated at high inflammation scores. HK2 protein expression was mostly restricted to brush border enterocytes, and these cells along with HK2 levels vanished with increasing disease severity. Conclusions: Our findings clearly define dysregulated epithelial HK2 expression as an indicator of disease activity in intestinal inflammation and suggest targeted HK2-inhibition as a potential therapeutic avenue. [ABSTRACT FROM AUTHOR]

Background: Coffee and tea consumption account for most caffeine intake and 2–3 billion cups are taken daily around the world. Caffeine dependence is a widespread but under recognized problem. Objectives: To conduct a systematic review on the genetic susceptibility factors affecting caffeine metabolism and caffeine reward and their association with caffeine intake. Methodology: We conducted PubMed and Embase searches using the terms "caffeine", "reward", "gene", "polymorphism", "addiction", "dependence" and "habit" from inception till 2024. The demographics, genetic and clinical data from included studies were extracted and analyzed. Only case-control studies on habitual caffeine drinkers with at least 100 in each arm were included. Results: A total of 2552 studies were screened and 26 studies involving 1,851,428 individuals were included. Several genes that were involved with caffeine metabolism such as CYP1A2, ADORA2A, AHR, POR, ABCG2, CYP2A6, PDSS2 and HECTD4 rs2074356 (A allele specific to East Asians and monomorphic in Europeans, Africans and Americans) were associated with habitual caffeine consumption with effect size difference of 3% to 32% in number of cups of caffeinated drink per day per effect allele. In addition, ALDH2 was linked to the Japanese population. Genes associated with caffeine reward included BDNF, SLC6A4, GCKR, MLXIPL and dopaminergic genes such as DRD2 and DAT1 which had around 2–5% effect size difference in number of cups of caffeinated drink for each allele per day. Conclusion: Several genes that were involved in caffeine metabolism and reward were associated with up to 30% effect size difference in number of cups of caffeinated drink per day, and some associations were specific to certain ethnicities. Identification of at-risk caffeine dependence individuals can lead to early diagnosis and stratification of at-risk vulnerable individuals such as pregnant women and children, and can potentially lead to development of drug targets for dependence to caffeine. [ABSTRACT FROM AUTHOR]

Phospholipids are the main building components of cell membranes and are also used for cell signaling and as energy storages. Cancer cells alter their lipid metabolism, which ultimately leads to an increase in phospholipids in cancer tissue. Surgical energy instruments use electrical or vibrational energy to heat tissues, which causes intra- and extracellular water to expand rapidly and degrade cell structures, bursting the cells, which causes the formation of a tissue aerosol or smoke depending on the amount of energy used. This gas phase analyte can then be analyzed via gas analysis methods. Differential mobility spectrometry (DMS) is a method that can be used to differentiate malignant tissue from benign tissues in real time via the analysis of surgical smoke produced by energy instruments. Previously, the DMS identification of cancer tissue was based on a 'black box method' by differentiating the 2D dispersion plots of samples. This study sets out to find datapoints from the DMS dispersion plots that represent relevant target molecules. We studied the ability of DMS to differentiate three subclasses of phospholipids (phosphatidylcholine, phosphatidylinositol, and phosphatidylethanolamine) from a control sample using a bovine skeletal muscle matrix with a 5 mg addition of each phospholipid subclass to the sample matrix. We trained binary classifiers using linear discriminant analysis (LDA) and support vector machines (SVM) for sample classification. We were able to identify phosphatidylcholine, -inositol, and -ethanolamine with SVM binary classification accuracies of 91%, 73%, and 66% and with LDA binary classification accuracies of 82%, 74%, and 72%, respectively. Phosphatidylcholine was detected with a reliable classification accuracy, but ion separation setups should be adjusted in future studies to reliably detect other relevant phospholipids such as phosphatidylinositol and phosphatidylethanolamine and improve DMS as a microanalysis method and identify other phospholipids relevant to cancer tissue. [ABSTRACT FROM AUTHOR]

Background: The possible role of the insulinemic potential of diet in the etiology of type 2 diabetes (T2D) has recently received significant attention in observational studies. This meta-analysis aimed to synthesize available evidence and quantify the potential association between the empirical dietary index for hyperinsulinemia (EDIH) score and T2D risk. Methods: Various electronic databases, including Scopus, PubMed, and Web of Science, were comprehensively searched up to January 2024 using related keywords to identify relevant studies. The hazard ratios (HR) or odds ratios were extracted from eligible cohort studies, and a random-effects model with an inverse variance weighting method was used to calculate the pooled effect size, which was expressed as HR. Results: The analysis included six cohort studies (four publications), with sample sizes ranging from 3,732 to 90,786 individuals aged 20 to 79 years. During follow-up periods of 5 to over 20 years, 31,284 T2D incidents were identified. The pooled results showed that a higher EDIH score was associated with an increased risk of T2D incidence (HR: 1.47; 95%CI 1.21–1.77; I2 = 91.3%). Significant publication bias was observed in the present meta-analysis (P = 0.020). Geographical region and follow-up period can be as sources of heterogeneity (Pheterogeneity <0.001). Conclusion: Our meta-analysis of observational studies suggested that a diet with a higher EDIH score may be associated with an increased risk of incidence of T2D. [ABSTRACT FROM AUTHOR]

Increased plasma creatine concentrations are associated with the risk of type 2 diabetes, but whether this alteration is associated with or causal for impairments in metabolism remains unexplored. Because skeletal muscle is the main disposal site of both creatine and glucose, we investigated the role of intramuscular creatine metabolism in the pathophysiology of insulin resistance in type 2 diabetes. In men with type 2 diabetes, plasma creatine concentrations were increased, and intramuscular phosphocreatine content was reduced. These alterations were coupled to reduced expression of sarcomeric mitochondrial creatine kinase 2 (CKMT2). In C57BL/6 mice fed a high-fat diet, neither supplementation with creatine for 2 weeks nor treatment with the creatine analog β-GPA for 1 week induced changes in glucose tolerance, suggesting that increased circulating creatine was associated with insulin resistance rather than causing it. In C2C12 myotubes, silencing Ckmt2 using small interfering RNA reduced mitochondrial respiration, membrane potential, and glucose oxidation. Electroporation-mediated overexpression of Ckmt2 in skeletal muscle of high-fat diet–fed male mice increased mitochondrial respiration, independent of creatine availability. Given that overexpression of Ckmt2 improved mitochondrial function, we explored whether exercise regulates CKMT2 expression. Analysis of public data revealed that CKMT2 content was up-regulated by exercise training in both humans and mice. We reveal a previously underappreciated role of CKMT2 in mitochondrial homeostasis beyond its function for creatine phosphorylation, independent of insulin action. Collectively, our data provide functional evidence for how CKMT2 mediates mitochondrial dysfunction associated with type 2 diabetes. Editor's summary: Increased plasma creatine is associated with type 2 diabetes, but causation has not been established. Rizo-Roca et al. show that men with type 2 diabetes had increased plasma creatine and decreased muscle phosphocreatine, which was associated with poor glucose handling. In myotubes in vitro, silencing the mitochondria-associated sarcomeric mitochondrial creatine kinase 2 (Ckmt2) gene resulted in impaired mitochondrial functions. In mice fed a high-fat diet, creatine supplementation had no effect on glucose handling, but overexpression of Ckmt2 in muscle improved mitochondrial functions. Data from humans and mice showed that exercise increased CKMT2 and metrics of mitochondrial functions. These results suggest that creatine changes are a consequence rather than a cause of insulin resistance in type 2 diabetes. —Brandon Berry [ABSTRACT FROM AUTHOR]

New particle formation (NPF) involving organic compounds has been identified as an important process affecting aerosol particle number concentrations in the global atmosphere. Laboratory studies have shown that highly oxygenated organic molecules (HOMs) can make a substantial contribution to NPF, but there is a lack of global model studies of NPF with detailed HOM chemistry. Here, we incorporate a state-of-the-art biogenic HOM chemistry scheme with 96 chemical reactions to a global chemistry–climate model and quantify the contribution to global aerosols through HOM-driven NPF. The updated model captures the frequency of NPF events observed at continental surface sites (normalized mean bias changes from - 96 % to - 15 %) and shows reasonable agreement with measured rates of NPF and sub-20 nm particle growth. Sensitivity simulations show that compared to turning off the organic nucleation rate, turning off organic initial growth results in a more substantial decrease in aerosol number concentrations. Globally, organics contribute around 45 % of the annual mean vertically integrated nucleation rate (at 1.7 nm) and 25 % of the vertically averaged growth rate. The inclusion of HOM-related processes leads to a 39 % increase in the global annual mean aerosol number burden and a 33 % increase in cloud condensation nuclei (CCN) burden at 0.5 % supersaturation compared to a simulation with only inorganic nucleation. Our work predicts a greater contribution of organic nucleation to NPF than previous studies due to the semi-explicit HOM mechanism and an updated inorganic NPF scheme. The large contribution of biogenic HOMs to NPF on a global scale could make aerosol sensitive to changes in biogenic emissions. [ABSTRACT FROM AUTHOR]

This case report presents a 38‐year‐old male patient who, after a febrile infection, developed super‐refractory status epilepticus and multiorgan failure, and died in 2 weeks despite the best possible intensive care. Autopsy revealed findings suggestive of hemophagocytic lymphohistiocytosis (HLH). This case shows that a rare immunological cause such as HLH may cause febrile infection‐related epilepsy syndrome (FIRES), and complications of intensive care can mask the physiological and laboratory changes in HLH. Plain Language Summary: This case report presents a 38‐year‐old man who, after a febrile infection, developed intractable epileptic activity requiring intensive care treatment. During the intensive care, the patient showed signs of multiple organ damage and died in 2 weeks despite the best possible treatment. Autopsy revealed findings suggestive of hemophagocytic lymphohistiocytosis (HLH), which is a rare immune system regulation disorder leading to persistent inflammatory state and organ damages. This case shows that an immunological disorder like HLH may underlie treatment resistant fever‐related epileptic seizures. [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation technique to activate or inhibit the activity of neurons, and thereby regulate their excitability. This technique has demonstrated potential in the treatment of neuropsychiatric disorders, such as depression. However, the effect of TMS on neurons with different severity of depression is still unclear, limiting the development of efficient and personalized clinical application parameters. In this study, a multi-scale computational model was developed to investigate and quantify the differences in neuronal responses to TMS with different degrees of depression. The microscale neuronal models we constructed represent the hippocampal CA1 region in rats under normal conditions and with varying severities of depression (mild, moderate, and major depressive disorder). These models were then coupled to a macroscopic TMS-induced E-Fields model of a rat head comprising multiple types of tissue. Our results demonstrate alterations in neuronal membrane potential and calcium concentration across varying levels of depression severity. As depression severity increases, the peak membrane potential and polarization degree of neuronal soma and dendrites gradually decline, while the peak calcium concentration decreases and the peak arrival time prolongs. Concurrently, the electric fields thresholds and amplification coefficient gradually rise, indicating an increasing difficulty in activating neurons with depression. This study offers novel insights into the mechanisms of magnetic stimulation in depression treatment using multi-scale computational models. It underscores the importance of considering depression severity in treatment strategies, promising to optimize TMS therapeutic approaches. [ABSTRACT FROM AUTHOR]

3 years of age is challenging. Among early risk factors, research has focused on having a positive familial history (FH+) for language or literacy problems and on late language emergence, that is, late-talker (LT) status. The interaction between these two risk factors and their cumulative effect is still debated. Here, we (a) investigate the effect of FH+ on 24-month language development, (b) test for cumulative effects of FH+ status and early language delay on 36-month language outcomes, and (c) disentangle the direct and indirect effects of familial history (FH) on the language outcome. Method: One hundred eighty-five Italian children were followed up longitudinally between 24 and 36 months of age (64 FH+ and 121 FH-) through parental questionnaires and direct child assessment. Results: At the age of 24 months, the FH+ group showed worse expressive vocabulary and higher prevalence of LT. At the age of 36 months, main effects of LT and FH were identified on lexical and phonological performances, respectively. Interestingly, significant interaction effects were identified on expressive vocabulary and phonological processing. Path analysis highlights that FH had a direct effect on later measures of phonology, whereas its effect on 36-month lexical abilities was indirect, via measures of expressive vocabulary at 24 months. Conclusions: The study suggests specific predictive roles of FH and LT status on language development. Interestingly, FH+ seems to represent an additive risk for LT children. The use of cumulative risk measures is confirmed as a powerful approach to identify those children with the highest probability of developing persistent language difficulties. [ABSTRACT FROM AUTHOR]

Background: The glucose transporter 2 (GLUT2) is constitutively expressed in pancreatic beta cells and hepatocytes of mice. It is the most important receptor in glucose-stimulated insulin release and hepatic glucose transport. The Sema4D is a signalin receptor on cell membranes. The correlation between Sema4D and GLUT2 has not been reported previously. We investigated whether knockdown of Sema4D could exert a hypoglycemic effect based on the increased GLUT2 expression in Sema4D -/- mice hepatocytes. Methods: The glucose tolerance test and insulin tolerance test in sema4D -/- and sema4D +/+ mice were compared before and after streptozotocin (STZ) injection; the expression of GLUT2 content on the membrane surface of both groups was verified by Western blot. Then, the levels of insulin and C-peptide in the serum of the two groups of mice after STZ injection were measured by ELISA; the differentially expressed mRNAs in the liver of the two groups of mice were analyzed by transcriptomic analysis; then the differences in the expression of GLUT2, glycogen, insulin and glucagon in the two groups of mice were compared by tissue section staining. Finally, metabolomics analysis was performed to analyze the metabolites differentially expressed in the two groups of mice. Key findings: First, Sema4D -/- male mice exhibited significantly greater glucose tolerance than wild-type mice in a hyperglycemic environment. Secondly, Sema4D -/- mice had more retained GLUT2 in liver membranes after STZ injection according to an immunofluorescence assay. After STZ injection, Sema4D -/- male mice did not exhibit fasting hyperinsulinemia like wild-type mice. Finally, analysis of metabolomic and immunohistochemical data also revealed that Sema4D -/- mice produce hypoglycemic effects by enhancing the pentose phosphate pathway, but not glycogen synthesis. Conclusions: Thus, Sema4D may play an important role in the regulation of glucose homeostasis by affecting GLUT2 synthesis. [ABSTRACT FROM AUTHOR]

Cistrome‐wide association studies (CWAS) are pivotal for identifying genetic determinants of diseases by correlating genetically regulated cistrome states with phenotypes. Traditional CWAS typically develops a model based on cistrome and genotype data to associate predicted cistrome states with phenotypes. The random effect cistrome‐wide association study (RECWAS), reevaluates the necessity of cistrome state prediction in CWAS. RECWAS utilizes either a linear model or marginal effect for initial feature selection, followed by kernel‐based feature aggregation for association testing is introduced. Through simulations and analysis of prostate cancer data, a thorough evaluation of CWAS and RECWAS is conducted. The results suggest that RECWAS offers improved power compared to traditional CWAS, identifying additional genomic regions associated with prostate cancer. CWAS identified 102 significant regions, while RECWAS found 50 additional significant regions compared to CWAS, many of which are validated. Validation encompassed a range of biological evidence, including risk signals from the GWAS catalog, susceptibility genes from the DisGeNET database, and enhancer‐domain scores. RECWAS consistently demonstrated improved performance over traditional CWAS in identifying genomic regions associated with prostate cancer. These findings demonstrate the benefits of incorporating kernel methods into CWAS and provide new insights for genetic discovery in complex diseases. [ABSTRACT FROM AUTHOR]

Cerebral aneurysms are abnormal dilations of blood vessels in the brain that have the potential to rupture, leading to subarachnoid hemorrhage and other serious complications. Early detection and prediction of aneurysm rupture are crucial for effective management and prevention of rupture-related morbidities and mortalities. This review aims to summarize the current knowledge on risk factors and predictive indicators of rupture in cerebral aneurysms. Morphological characteristics such as aneurysm size, shape, and location, as well as hemodynamic factors including blood flow patterns and wall shear stress, have been identified as important factors influencing aneurysm stability and rupture risk. In addition to these traditional factors, emerging evidence suggests that biological and genetic factors, such as inflammation, extracellular matrix remodeling, and genetic polymorphisms, may also play significant roles in aneurysm rupture. Furthermore, advancements in computational fluid dynamics and machine learning algorithms have enabled the development of novel predictive models for rupture risk assessment. However, challenges remain in accurately predicting aneurysm rupture, and further research is needed to validate these predictors and integrate them into clinical practice. By elucidating and identifying the various risk factors and predictive indicators associated with aneurysm rupture, we can enhance personalized risk assessment and optimize treatment strategies for patients with cerebral aneurysms. [ABSTRACT FROM AUTHOR]

Air ions are electrically charged particles in air. They are ubiquitous in the natural environment and affect the Earth's radiation budget by accelerating the formation and growth of new aerosol particles. Despite this, few datasets exist exploring these effects in the urban environment. A neutral cluster and air ion spectrometer was deployed in Leipzig, Germany, to measure the number size distribution of charged particles from 0.8 to 42 nm, between 27 July and 25 August 2022. Following previous analyses, charged particles were classified into small (0.8–1.6 nm), intermediate (1.6–7.5 nm), and large (7.5–22 nm) fractions by mass diameter, and their mean concentrations (sum of positive and negative polarities) during the campaign were 405, 71.6, and 415 cm -3 , respectively. The largest peaks in intermediate and large ions were explained by new particle formation (NPF), with intermediate ions correlating well with sulfuric acid dimer. Smaller morning and evening peaks were coincident with black carbon concentrations and attributed to primary emissions. NPF events, observed on 30 % of days, coincided with intense solar radiation and elevated sulfuric acid dimer. Small charged particles were primarily associated with radioactive decay and highest during the early hours, and they are unrelated to primary emissions or NPF. The apparent contributions of charged particles to 3 and 7.5 nm particle formation rates were 5.7 % and 12.7 %, respectively, with mean growth rates of 4.0 nm h -1 between 3–7.5 nm and 5.2 nm h -1 between 7.5 and 22 nm. The ratio of charged to total particle formation rates at 3 nm suggests a minor role for charged particles in NPF. We conclude that NPF is a primary source of > 3 nm ions in our data, with primary emissions being the major source in the absence of NPF. [ABSTRACT FROM AUTHOR]

Bioaerosols, including airborne bacteria, are significant pollutants affecting both indoor and outdoor air quality, with implications for human health. Despite extensive research on indoor air quality, there is a notable lack of comprehensive data on ambient bacterial concentrations and their interactions with pollutants and meteorological factors. This review focuses on bacterial aerosols in the atmosphere, measured using the culture-based method, considered the "gold standard" for microorganism detection and identification. Studies reveal significant variability in bacterial concentrations across different environments and seasons, influenced by factors such as temperature, humidity, wind speed, solar radiation, and precipitation, underscoring the need for further research and monitoring to enhance health risk assessments and mitigation strategies. The presence of air pollutants such as particulate matter (PM) and ozone (O3) further complicates these dynamics. The authors emphasize the need for more extensive research on outdoor bacterial aerosols and recommend that future studies prioritize detailed bioaerosol characterization to establish comprehensive exposure standards in ambient air, thereby improving public health protection and environmental management practices. [ABSTRACT FROM AUTHOR]

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Stereotactic radiosurgery (SRS) is an effective treatment strategy for cerebral arteriovenous malformations (AVMs). Aggressive treatment achieving complete obliteration is necessary to prevent further intracranial hemorrhage and neurological deficits. However, SRS treatment of large AVMs (>10 cm3) is challenging. To prevent toxicity in the normal brain tissue, it is imperative to reduce the radiation dose as the lesion volume increases; however, this also reduces the rate of obliteration. In this study, we review the various radiosurgical approaches for treating large AVMs and their outcomes, and suggest ways to improve treatment outcomes during SRS for large AVMs. [ABSTRACT FROM AUTHOR]

Assessing physical activity and cardiometabolic risk in masters athletes as an example of very high physical activity at old age. Forty-three men were studied in full factorial design, either as sprint or jump-trained masters athletes (MA, n=10, age 60–75 years), as young sprint or jump-trained athletes (YA, n=10, age 20–35 years), older control participants (OC, n=11, age 60–75 years) or as young control participants (AC, n=12, age 20–35 years). We performed bio-electrical impedance analysis and assessed serum markers of lipids and glucose metabolism and C-reactive protein, structured training hours, and habitual activity via mobile actimetry. Body fat was greater in OC than in MA (23.9 [SD 4.2] % vs. 14.0 [SD 5.7] %, p<0.001), and also greater than in YA and YC (both p<0.001). Weekly training hours were comparable between MA and YA (7.9 [SD3.3] hours vs. 11.1 [SD 4.8] hours, p=0.69). Habitual walking distance was greater in MA than in OC (7,387 [SD 4,923] m/day vs. 4,110 [SD 1,772] m/day, p=0.039), and so was habitual running distance (667 [SD690] m/day vs. 132 [427] m/day, p<0.001). HOMA-index was greater in OC than in MA (2.07 [SD 1.39] vs. 0.80 [SD 0.41], p=0.0039), and so was C-reactive protein (1.35 [SD 1.74] mg/l vs. 0.58 [SD 0.27] mg/ml, p=0.018), whereas serum lipids showed only moderate or no effect (all p between 0.036 and 0.07). Improved body composition and physical activity levels in MA are associated with lower cardiometabolic risk, which seems more pronounced for insulin sensitivity and inflammaging than for lipid metabolism. [ABSTRACT FROM AUTHOR]

The regulation of emotions is a crucial facet of well‐being and social adaptability, with explicit strategies receiving primary attention in prior research. Recent studies, however, emphasize the role of implicit emotion regulation, particularly implicating the ventromedial prefrontal cortex (VMPFC) in association with its implementation. This study delves into the nuanced role of the VMPFC through focality‐optimized multichannel transcranial direct current stimulation (tDCS), shedding light on its causal involvement in implicit reappraisal. The primary goal was to evaluate the effectiveness of VMFPC‐targeted tDCS and elucidate its role in individuals with high trait anxiety. Participants engaged in implicit and explicit emotion regulation tasks during multichannel tDCS targeting the VMPFC. The outcome measures encompassed negative emotion ratings, pupillary diameter, and saccade count, providing a comprehensive evaluation of emotion regulation efficiency. The intervention exhibited a notable impact, resulting in significant reductions in negative emotion ratings and pupillary reactions during implicit reappraisal, highlighting the indispensable role of the VMPFC in modulating emotional responses. Notably, these effects demonstrated sustained efficacy up to 1 day postintervention. This study underscores the potency of VMPFC‐targeted multichannel tDCS in augmenting implicit emotion regulation. This not only contributes insights into the neural mechanisms of emotion regulation but also suggests innovative therapeutic avenues for anxiety disorders. The findings present a promising trajectory for future mood disorder interventions, bridging the gap between implicit emotion regulation and neural stimulation techniques. [ABSTRACT FROM AUTHOR]

Alpha-1 adrenergic receptor (α1-AR) antagonists are commonly used for management of benign prostatic hyperplasia or hypertension. Some studies have shown a potential link between α1-AR antagonist use and cognitive impairment. Given the conflicting data surrounding α1-AR antagonists association with cognitive dysfunction, we aim to systematically review the association of cognitive dysfunction with α1-AR antagonist use to aid clinician decision both with medication initiation and continuation. A systematic review was performed following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. We searched Ovid Cochrane, Ovid Embase, Ovid MEDLINE, Scopus, and Web of Science on March 7, 2023, with an update run on January 22, 2024. The primary outcome was cognitive dysfunction. We used Cochrane risk of bias for randomized controlled trials (RCTs) and MINORS (Methodological Index for Non-Randomized Studies) criteria for non-RCTs to evaluate study quality. This study was registered with PROSPERO (CRD42024505751). We identified 7 studies for our systematic review (3 RCTs, 4 non-RCTs). Tamsulosin was the most studied medication (6 of 7 studies). Tamsulosin was associated with no cognitive dysfunction in 2 RCTs, increased risk for dementia in 2 non-RCTs, no change in cognition in 1 non-RCT, and decreased risk for dementia in 1 non-RCT. Among 3 non-RCTs analyzing alfuzosin, it was associated with decreased risk of or no association with dementia in 2 studies and increased risk for dementia in 1 study. Doxazosin, prazosin, and terazosin were neutral or showed a negative risk for dementia. Our systematic review did not show a convincing causal association between α1-AR antagonists, including tamsulosin, and cognitive dysfunction. Considering the existing literature, it is appropriate to use α1-AR antagonists without concern for cognitive dysfunction. Future research, through robust study designs considering the multifactorial nature of cognitive dysfunction, is required to further evaluate this association. [ABSTRACT FROM AUTHOR]

Salvia elegans Vahl is a plant commonly used in Mexico as a remedy for nervous disorders, inflammatory diseases, and "ringing in the ears"; the latter can be associated with arteriosclerotic conditions and arterial hypertension. Therefore, based on medicinal use, this work aimed to evaluate the hydroalcoholic extract (SeHA, 100 mg/kg) of this plant and two fractions, ethyl acetate (SeFAc, 50 mg/kg), and obtained from SeFAc fractionation denominated SeF3 (10 mg/kg), on several alterations derived from metabolic syndrome (MetS) derived from the ingestion of a high-calorie diet (high-fat diet), in ICR (Institute of Cancer Research) mice, leading to chronic inflammation that results in neurological damage such as depression. Therefore, several MetS-related parameters, such as forced swim tests, hypertension, serum corticosterone levels, glucose, triglycerides, cholesterol, adiposity index, and insulin resistance, will be evaluated. Additionally, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-10 levels were measured in kidneys, fat tissue, brains, and spleens. It was proven that all those S. elegans-derived treatments reversed the damage, showing antidepressant, antihypertensive, antihyperglycemic, and antidyslipidemic effects and decreased adiposity, insulin resistance, and serum corticosterone. They induced a modulatory response by modifying the levels of TNF-α, IL-1β, IL-6, and IL-10 in different organs. High-performance liquid chromatography (HPLC) analysis of the acetate of ethyl fraction from S. elegans (SeFAc) fraction revealed the presence of rosmarinic and caffeic acids as well as flavonoids, while the fraction from SeFAc called SeF3 Was identified by gas mass as methyl glucose, glycerol, and known sterols, among others. Thus, it was concluded that S. elegans protects against the harmful effects of MetS. [ABSTRACT FROM AUTHOR]