Notes

Intestinal tract Microbiota, Obesity and also Prebiotics.
To evaluate the distribution of circulating immune cell subsets in peripheral blood of patients with sarcoidosis and investigate if there is an association with an underlying cardiac involvement.

Eighty-five newly diagnosed treatment-naïve patients with sarcoidosis (50 women) were included in the study. All patients underwent a thorough cardiac investigation, including cardiac magnetic resonance imaging (CMR). Of all patients, 19 (23.53%) had myocardial involvement, and the NK subpopulation in these patients in peripheral blood was significantly decreased compared to patients without (n=63, p=0.001 and p=0.003 respectively). The absolute number of NKT cells (CD3+CD16/56
) in patients with cardiac involvement was highly correlated with T2map increased values in MRI (r=-686, p=0.041) showing that low NKT cell count correlates with the inflammatory process of the heart. No difference in CD19, CD3, CD4, CD8 and CD3
NK cell counts was found between groups. Lung severity was not found to correlate with the number of NK cells.

We found that low NK cell count in peripheral blood of patients with sarcoidosis is associated with cardiac involvement, and the number of NK-T cells correlates with CMR findings indicative of myocardial inflammation. This finding might have a potential clinical application in detecting clinically silent cardiac involvement in sarcoidosis and may also suggest potential targets for therapeutic interventions.
We found that low NK cell count in peripheral blood of patients with sarcoidosis is associated with cardiac involvement, and the number of NK-T cells correlates with CMR findings indicative of myocardial inflammation. This finding might have a potential clinical application in detecting clinically silent cardiac involvement in sarcoidosis and may also suggest potential targets for therapeutic interventions.Decline in immune function during aging increases susceptibility to different aging-related diseases. However, the underlying molecular mechanisms, especially the genetic factors contributing to imbalance of naïve/memory T-cell subpopulations, still remain largely elusive. Here, we show that loss of DJ-1 encoded by PARK7/DJ-1, causing early-onset familial Parkinson's disease (PD), unexpectedly diminished signs of immunoaging in T-cell compartments of both human and mice. Compared with two gender-matched unaffected siblings of similar ages, the index PD patient with DJ-1 deficiency showed a decline in many critical immunoaging features, including almost doubled non-senescent T cells. The observation was further consolidated by the results in 45-week-old DJ-1 knockout mice. Our data demonstrated that DJ-1 regulates several immunoaging features via hematopoietic-intrinsic and naïve-CD8-intrinsic mechanisms. Mechanistically, DJ-1 depletion reduced oxidative phosphorylation (OXPHOS) and impaired TCR sensitivity in naïve CD8 T cells at a young age, accumulatively leading to a reduced aging process in T-cell compartments in older mice. Our finding suggests an unrecognized critical role of DJ-1 in regulating immunoaging, discovering a potent target to interfere with immunoaging- and aging-associated diseases.
The desire-goal motivational conflict helps explain endurance performance; however, the physiological concomitants are unknown. The present study examined disturbances in desire to reduce effort and performance goal value across moderate, heavy, and severe exercise intensity domains, demarcated by the first (LT1) and second (LT2) lactate thresholds. In addition, the within-person relationships among blood lactate concentration, heart rate, and desire-goal conflict were examined.

Thirty participants (53% female, M
=21.03years; SD=2.06years) completed an incremental cycling exercise test, in which work rate was increased by 25 watts every four minutes, until voluntary exhaustion or sufficient data from the severe intensity domain had been collected. Desire to reduce effort, performance goal value, blood lactate concentration (for determination of LT1 and LT2), and heart rate were measured at the end of each stage and analyzed using multilevel models.

The desire to reduce effort increased over the exercie influential for motivation, compared with heart rate.People typically have a strong bias in attention toward faces to help them understand social interactions. Nonetheless some people, like incarcerated offenders and psychopaths, exhibit deficits in "face reading," which may impair their interpretations, especially in case of attribution allocation in harmful events. In these cases, the ascription of intentionality is key in understanding the allocation of blame and structuring social information processing. Consequently, in the current study, in addition to typically studied intentionality and blame ascription levels (subfactors of hostile attributions), we also propose a new indicator of hostile attributions intentionality/blame isomorphism, indicating reduced differentiation between those two factors. Violent prison inmates (N = 63) and community-based adults without previous history of incarceration (N = 63) took part in an eye-tracking study. In line with our hypotheses, offenders exhibited reduced attention orienting to faces as well as greater intentionality/blame isomorphism. In the case of both groups, people looked longer at the faces of the harm doer compared with the harm receiver. Additionally, greater intentionality/blame isomorphism predicted reduced attention to faces; however, when group status was included in the model, it became the only significant predictor of the attention to faces. Future studies should examine the origins of these gaze and attribution patterns and investigate consequences related to social perception and interactions of people prone to violence.Compounds bearing aliphatic amines can be emissive under appropriate conditions. However, their ionized counterparts, namely, quaternary ammonium salts (QASs), which are widely used as phase-transfer catalysts, ionic liquids, disinfectants, and surfactants, are known as luminescence quenchers and considered nonemissive. Herein, unprecedented intrinsic fluorescence/phosphorescence dual emissions from various QASs are reported, which can be finely regulated by changing the excitation wavelength, alkyl chain length, counterion, and mechanical stimuli. The bright photoluminescence along with distinct afterglow and tunable multicolor emissions enables the application of QAS solids in advanced multimode anticounterfeiting. This finding refreshes the understanding of QASs and may inspire emerging applications based on the utilization of the intrinsic luminescences of QASs. Furthermore, it opens opportunities for the investigation of QAS-related processes and functions via a photophysical approach and affords strong implications for the fabrication of novel nonconventional luminophores.
This study investigates the effects of PRAX-562 on sodium current (I
), intrinsic neuronal excitability, and protection from evoked seizures to determine whether a preferential persistent I
inhibitor would exhibit improved preclinical efficacy and tolerability compared to two standard voltage-gated sodium channel (Na
) blockers.

Inhibition of I
was characterized using patch clamp analysis. The effect on intrinsic excitability was measured using evoked action potentials recorded from hippocampal CA1 pyramidal neurons in mouse brain slices. Anticonvulsant activity was evaluated using the maximal electroshock seizure (MES) model, and tolerability was assessed by measuring spontaneous locomotor activity (sLMA).

PRAX-562 potently and preferentially inhibited persistent I
induced by ATX-II or the SCN8A mutation N1768D (half-maximal inhibitory concentration [IC
] = 141 and 75nmol·L
, respectively) relative to peak I
tonic/resting block (60× preference). PRAX-562 also exhibited potent use-dependNa
blockers (CBZ and LTG), potentially due to the preference for persistent I
. Preferential targeting of persistent I
may represent a differentiated therapeutic option for diseases of hyperexcitability, where standard Na
blockers have demonstrated efficacy but poor tolerability.
PRAX-562 demonstrated robust preclinical anticonvulsant activity similar to CBZ but improved compared to LTG. PRAX-562 exhibited significantly improved preclinical tolerability compared with standard NaV blockers (CBZ and LTG), potentially due to the preference for persistent INa . Preferential targeting of persistent INa may represent a differentiated therapeutic option for diseases of hyperexcitability, where standard NaV blockers have demonstrated efficacy but poor tolerability.Accurate age-at-death estimation is important for both paleodemographic studies and forensic casework. Although the auricular surface of the ilium is a well-validated skeletal indicator for aging studies, problems persist with identifying features that estimate age accurately in older individuals. This study tests the utility of one method, developed by Igarashi et al. (2005), which claims to estimate age more accurately in older individuals using a presence/absence scoring system for 13 auricular surface traits. Four hundred (400) individuals, aged 16-93 years, from the Hamann-Todd Collection were examined to test the performance of Igarashi et al.'s method in a North American sample. Pearson's product-moment correlation tests were performed for both the overall method and individual traits to assess correlation with chronological age. Eleven of the 13 traits showed statically significant correlations with chronological age, and nine were found to have higher correlations than originally reported. The method showed a tendency toward negative bias (i.e., a tendency to under-age individuals, particularly in the older age range). Models for both males and females and full and reduced models developed by Igarashi et al. were tested; the sex-pooled full model performed best, and the female full model performed most poorly. Although this method did not have significantly higher accuracy rates in a North American sample than other auricular surface methods, unique traits identified by Igarashi et al. did correlate with chronological age. In future studies, these traits should be investigated using different scoring systems (e.g., character states), as they show utility for aging research.Transition metal-based electrocatalysts will undergo surface reconstruction to form active oxyhydroxide-based hybrids, which are regarded as the "true-catalysts" for the oxygen evolution reaction (OER). Much effort has been devoted to understanding the surface reconstruction, but little on identifying the origin of the enhanced performance derived from the substrate effect. Herein, we report the electrochemical synthesis of amorphous CoOOH layers on the surface of various cobalt sulfides (CoSα ), and identify that the reduced intermolecular energy gap (Δinter ) between the valence band maximum (VBM) of CoOOH and the conduction band minimum (CBM) of CoSα can accelerate the formation of OER-active high-valent Co4+ species. The combination of electrochemical and in situ spectroscopic approaches, including cyclic voltammetry (CV), operando electron paramagnetic resonance (EPR) and Raman, reveals that Co species in the CoOOH/Co9 S8 are more readily oxidized to CoO2 /Co9 S8 than in CoOOH and other CoOOH/CoSα . This work provides a new design principle for transition metal-based OER electrocatalysts.
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