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Epidemiological evidence of the association between migraines, severe headaches, and hypertension is contradictory. Hypertension is a critical risk factor for cardiovascular diseases. Migraine is a common neurological disease and a major cause of disability worldwide. Therefore, we aimed to investigate the relationship between migraine, severe headaches, and hypertension among US adults.Cross-sectional data from 5716 subjects were obtained from the National Health and Nutrition Examination Survey between 1999 and 2004. Weighted logistic regression models investigated the association between migraines, severe headaches, and hypertension. In total, 5716 subjects were enrolled in the present study, of whom 1134 (19.8%) had migraine or severe headaches. Participants with migraine were predominantly younger females and had a higher body mass index (BMI), lower educational level, lower dietary intake of potassium and calcium, lower serum levels of total cholesterol (TC), creatinine, and hemoglobin, as well as a higher estimated glomerular filtration rate (eGFR) (all P 0.05). After fully adjusting for potential confounders, migraine or severe headaches were positively associated with hypertension (OR 1.25, 95% CI: 1.03-1.53).Our study found a positive association between migraine, severe headaches, and hypertension. Further studies are needed to verify the causality of this association and elucidate the underlying mechanisms.

Sleep loss is often associated with cognitive dysfunction. Alterations in the structure and function of synapses in the hippocampus are thought to underlie memory storage. Paired immunoglobulin-like receptor B (PirB) plays a negative role in various neurological diseases by inhibiting axon regeneration and synaptic plasticity. However, the contributions of PirB to the mechanisms underlying the changes in synaptic plasticity after sleep loss that ultimately promote deficits in cognitive function have not been well elucidated. Here, we showed that chronic sleep restriction (CSR) mice displayed cognitive impairment and synaptic deficits accompanied by upregulation of PirB expression in the hippocampus. Mechanistically, PirB caused the dysregulation of actin through the RhoA/ROCK2/LIMK1/cofilin signalling pathway, leading to abnormal structural and functional plasticity, which in turn resulted in cognitive dysfunction. PirB knockdown alleviated synaptic deficits and cognitive impairment after CSR by inhibiting the RhoA/ROCK2/LIMK1/cofilin signalling pathway. Moreover, we found that fasudil, a widely used ROCK2 inhibitor, could mimic the beneficial effect of PirB knockdown and ameliorate synaptic deficits and cognitive impairment, further demonstrating that PirB induced cognitive dysfunction after CSR via the RhoA/ROCK2/LIMK1/cofilin signalling pathway. Our study sheds new light on the role of PirB as an important mediator in modulating the dysfunction of synaptic plasticity and cognitive function via the RhoA/ROCK2/LIMK1/cofilin signalling pathway, which indicated that hippocampal PirB is a promising therapeutic target for counteracting cognitive impairment after CSR. Graphical Abstract This illustration depicts the signalling pathway by PirB in mediating cognitive impairment and synaptic deficits in CSR mice. In the hippocampus of CSR mice, the expression level of PirB was significantly increased. In addition, CSR increases RhoA and ROCK2 levels and reduces levels of both LIMK1 and cofilin phosphorylation. PirB knockdown reverses cognitive impairment and synaptic plasticity disorders caused by CSR through the RhoA/ROCK2/LIMK1/cofilin signalling pathway

Traumatic haemorrhage (TH) is the leading cause of potentially preventable deaths that occur during the prehospital phase of care. No effective pharmacological therapeutics are available for critical TH patients yet. Here, we identify terminal complement activation (TCA) as a therapeutic target in combat casualties and evaluate the efficacy of a TCA inhibitor (nomacopan) on organ damage and survival in vivo.Complement activation products and cytokines were analysed in plasma from 54 combat casualties. The correlations between activated complement pathway(s) and the clinical outcomes in trauma patients were assessed. Nomacopan was administered to rats subjected to lethal TH (blast injury and haemorrhagic shock). Effects of nomacopan on TH were determined using survival rate, organ damage, physiological parameters, and laboratory profiles.Early TCA was associated with systemic inflammatory responses and clinical outcomes in this trauma cohort. Lethal TH in the untreated rats induced early TCA that correlated with the severity of tissue damage and mortality. The addition of nomacopan to a damage-control resuscitation (DCR) protocol significantly inhibited TCA, decreased local and systemic inflammatory responses, improved haemodynamics and metabolism, attenuated tissue and organ damage, and increased survival.Previous findings of our and other groups revealed that early TCA represents a rational therapeutic target for trauma patients. Nomacopan as a pro-survival and organ-protective drug, could emerge as a promising adjunct to DCR that may significantly reduce the morbidity and mortality in severe TH patients while awaiting transport to critical care facilities.

The gut microbiota seems to be a major modulator of cardiovascular diseases, such as myocardial infarction. Dapagliflozin, a sodium glucose cotransporter 2 inhibitor (SGLT2i), is an antidiabetic agent that was recently utilized in patients with cardiovascular diseases. This study aims to investigate the effects of dapagliflozin on the faecal microbiota of postinfarction non-diabetic mice. A total of 19 male mice were randomly divided into three groups, where two groups were enduced with myocardial infarction (MI) by left anterior descending ligation. One day after the surgery, each group was administered normal saline (15 mL/kg/day, 0.9%) or dapagliflozin (1.5 mg/kg/day) for 4 weeks. Echocardiography was obtained on day 28 post MI. Masson's trichrome staining was used to determine the degree of fibrosis. Faecal samples were collected to assess the microbiome by 16S ribosomal RNA gene sequencing. We found that dapagliflozin significantly improved cardiac function in the non-diabetic myocardial infarction mice model after the 28-day treatment, especially in ejection fraction and fractional shortening (p 0.01). Enterotypes were composed of Muribaculaceae and Lactobacillaceae after dapagliflozin treatment, while Muribaculaceae and Erysipelotrichaceae were the main enterotypes post-MI. Dapagliflozin increased the abundance of beneficial bacteria like Lactobacillaceae, while decreasing the abundance of beneficial bacteria like Bifidobacteriaceae. It was interesting to discover that Proteobacteria (especially Desulfovibrionaceae) were enriched after the dapagliflozin treatment for myocardial infarction. Dapagliflozin increased the abundance of the main beneficial bacteria. In post-myocardial infarction treatments, using dapagliflozin could positively contribute to the improvement of cardiac function and alter the structure of faecal microbiota.

Averaging amplitudes over consecutive time samples (i.e., time window) is widely used to calculate the peak amplitude of event-related potentials (ERPs). Cluster analysis of the spatio-temporal ERP data is a promising tool to determine the time window of an ERP of interest. However, determining an appropriate number of clusters to optimally represent ERPs is still challenging. Here, we develop a new method to estimate the optimal number of clusters utilizing consensus clustering. Various polarity dependent clustering methods, namely, k-means, hierarchical clustering, fuzzy c-means, self-organizing map, spectral clustering, and Gaussian mixture model, are used to configure consensus clustering after assessing them individually. When a range of clusters is applied many times, the optimal number of clusters should correspond to the expectation, which is the average of the obtained mean inner-similarities of estimated time windows across all conditions and groups converge in the satisfactory thresholds. In order to assess our method, the proposed method has been applied to simulated data and prospective memory experiment ERP data aimed to qualify N2 and P3, and N300 and prospective positivity components, respectively. The results of determining the optimal number of clusters meet at six cluster maps for both ERP data. In addition, our results revealed that the proposed method could be reliably applied to ERP data to determine the appropriate time window for the ERP of interest when the measurement interval is not accurately defined.

Paralytic ileus is common in patients with septic shock, causing high morbidity and mortality. Enteric neurons and enteric glial cells (EGCs) regulate intestinal motility. However, little is known about their interaction in endotoxemia. This study aimed to investigate whether reactive EGCs had harmful effects on enteric neurons and participated in intestinal motility disorder in mice during endotoxemia. Endotoxemia was induced by the intraperitoneal injection of lipopolysaccharide (LPS) in mice. Fluorocitrate (FC) was administered before LPS injection to inhibit the reactive EGCs. The effects of reactive EGCs on intestinal motility were analyzed by motility assays in vivo and colonic migrating motor complexes ex vivo. The number of enteric neurons was evaluated by immunofluorescent staining of HuCD, nNOS, and ChAT in vivo. In addition, we stimulated EGCs with IL-1β and TNF-α in vitro and cultured the primary enteric neurons in the conditioned medium, detecting the apoptosis and morphology of neurons through staining TUNEL, cleaved caspase-3 protein, and anti-β-III tubulin. Intestinal motility and peristaltic reflex were improved by inhibiting reactive EGCs in vivo. The density of the neuronal population in the colonic myenteric plexus increased significantly, while the reactive EGCs were inhibited, especially the nitrergic neurons. In vitro, the enteric neurons cultured in the conditioned medium of reactive EGCs had a considerably higher apoptotic rate, less dendritic complexity, and fewer primary neurites. Reactive enteric glial cells probably participated in paralytic ileus by damaging enteric neurons during endotoxemia. They might provide a novel therapeutic strategy for intestinal motility disorders during endotoxemia or sepsis.

Given that sexual behavior is usually pleasurable and highly rewarding, it is surprising that there is as yet no known research to empirically assess how premature ejaculation (PE) patients respond to the rewarding aspect of sexual behavior. This study was designed to address this issue by evaluating how these men respond to the anticipation and hedonic experience of sexual rewards in comparison to non-sexual rewards. Thirty lifelong PE patients and thirty healthy controls (HCs) performed the incentive delay task manipulating both erotic and monetary rewards. Compared to HCs, lifelong PE patients exhibited significantly faster RTs to erotic cues than to monetary cues during reward anticipation. Meanwhile, hedonic experience ratings after obtaining the actual reward showed that erotic rewards were rated as more pleasant than monetary rewards only by lifelong PE patients. These findings indicate the existence of dysfunctional reward processing in lifelong PE patients, which is characterized by increased incentive motivation elicited by sexual cues and enhanced hedonic impact of sexual rewards. This study may offer an insightful clue regarding how PE is related to the abnormal regulation of the rewarding aspect of sexual behavior.

Background Multiple lines of research suggests that dysregulation in the dopaminergic system may contribute to migraine pain. However, it is only in recent years that researchers have begun to investigate this by exploring how the system is dysregulated during incentive processing in migraineurs. Still little is known about the pathophysiological changes in incentive processing along the temporal scale in migraineurs. Therefore, the present study examined migraine-related changes in neural processing implicated in incentive anticipation and its delivery.Methods A total of 19 episodic migraine (EM) patients (mean age = 31.95 ± 1.42, 17 females) and 19 healthy controls (HCs) (mean age = 30.16 ± 0.98, 16 females) underwent a monetary incentive delay (MID) task, while event-related potentials (ERPs) were recorded in their brains.Results Electrophysiologically, during the incentive anticipation phase, both Cue-N2 and Cue-P3 amplitudes were of higher magnitude for the reward-anticipation and punishment-anticipation cues compared to the control cue across both groups. This indicates no significant differences in neural activity supporting incentive/no incentive cue evaluation between groups. During the outcome phase, the amplitude of the FRN, an ERP component related to performance evaluation, was significantly larger for punishing feedback than rewarding feedback across both groups. However, the Feedback-P3 amplitude, an ERP component related to attentional processing of motivational value of outcome feedback, was significantly larger for rewarding feedback than punishing feedback in HCs, but not in EM patients. Moreover, a negative correlation was observed between the Feedback-P3 amplitude difference for rewarding minus punishing feedback and subjective pain intensity measured by the VAS in EM patients. Finally, the amplitude of the Feedback-LPP, an ERP component related to attentional processing of the affective value of outcome feedback, was significantly larger for punishing feedback than rewarding feedback only in HCs, but not in EM patients.Conclusions Our findings suggest that pathophysiological changes in incentive processing may act as a core mechanism underlying migraine pathophysiology. This study may also provide sensitive and reliable biomarkers for evaluating the efficacy of migraine therapeutics.

Zhen Luo,1 Yansong Li,2 Xiaoqiang Li,1 Ren Liao1 1Department of Anesthesiology, Sichuan University West China Hospital, Chengdu, People’s Republic of China; 2Department of Anesthesiology, Center for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of ChinaCorrespondence: Xiaoqiang Li, Email 39006900@qq.comObjective: The optimal red blood cell transfusion strategy for children remains unclear. We developed an individualized red blood cell transfusion strategy for children and tested the hypothesis that transfusion guided by this strategy could reduce blood exposure, without increasing perioperative complications in children.Methods: In this randomized controlled clinical trial, 99 children undergoing noncardiac surgeries who had blood loss of more than 20% total blood volume were randomly assigned to an individualized-strategy group using Pediatric Perioperative-Transfusion-Trigger Score or a control group. The amount of transfused red blood cell was counted, and patients were followed up for postoperative complications within 30 days.Results: Twenty-six children (53.1%) in the individualized-strategy group received transfusion perioperatively, as compared with 37 children (74%) in the control group (p < 0.05). During surgery, children in the individualized-strategy group were exposed to fewer transfusions than in the control group (0.87± 1.03 vs 1.33± 1.20 Red-Blood-Cell units per patient, p = 0.02). The incidence of severe complications in the individualized-strategy group had a lower trend compared to the control group (8.2% vs 18%, p = 0.160). No significant difference was found in the other outcomes.Conclusion: This trial proved that red blood cell transfusion guided by the individualized strategy reduced perioperative blood exposure in children, without increasing the incidence of severe complications. This conclusion needs to be reaffirmed by larger-scale, multicenter clinical trials.Keywords: red blood cell, transfusion strategy, perioperative red blood cell transfusion, pediatrics, hemoglobin concentration

Non-spherical particles exhibit peculiar behaviour in non-Newtonian flows. In this paper, we numerically investigate the dynamics of a neutrally buoyant prolate spheroid immersed in viscoelastic shear flows at finite Reynolds numbers by means of the immersed boundary method. Our results show that the period of particle rotation changes monotonically with the solvent viscosity ratio but non-monotonically with the mobility factor. Furthermore, we find five rotation modes of the spheroid under the effects of fluid inertia and fluid rheology in the present flow configuration. With weak fluid inertia, the particle rotation rate is remarkably reduced by fluid elasticity, which also induces asymmetric rotational behaviour. While the particle tends to tumble in the shear plane with weak fluid elasticity and moderate fluid inertia. However, as the fluid elasticity increases, the particle rotates with a newly observed mode, named the asymmetric-kayaking mode, which is classified by two additional critical elastic numbers that differ from the earlier studies on Stokesian viscoelastic shear flows. The present findings imply the importance of fluid inertia and fluid elasticity on the particle dynamics and could be potentially used to control the particle orientations in viscoelastic fluid flows.

Mitochondrial redox imbalance has been recognized as a unifying cause for diabetic cognitive impairment. Currently, a robust method for the in vivo assessment of brain mitochondrial redox imbalance is still lacking. Here, we conducted a spectral study to assess brain mitochondrial redox imbalance in the process of diabetic cognitive impairment by using label-free resonance Raman spectroscopy (RRS). Our findings showed that mitochondrial redox imbalance in cultured neurons and organotypic cortical slices exposed to high glucose were quantified by the reduction of Raman peak area at 750 cm

The prevalence of diabetes-associated cognitive dysfunction (DACD) has increased to 13.5%. Dementia, as the most severe DACD, is the second leading cause of death in patients with diabetes mellitus. Hence, the potential mechanisms of DACD for slowing or halting its progression need to be urgently explored. Given that the sigma-1 receptor (Sig-1R), a chaperone protein located in the endoplasmic reticulum (ER)-mitochondrion contact membranes to regulate ER stress (ERS), is associated with cognitive outcomes in neurodegenerative diseases, this study aimed to investigate the role of astrocytic Sig-1R in DACD and its underlying mechanism. Here, we examined the levels of ERS and complement component 3/3a (C3/C3a) from primary astrocytes with different concentrations of glucose and treatment. Subsequently, HT22 neurons were cultured in different astrocyte-conditioned medium, and the expression of synaptic proteins was detected. We constructed type 1 diabetes mellitus (T1DM) model to evaluate the astrocytic Sig-1R mechanism on synapse and cognitive function changes. In vitro, high glucose concentration downregulated Sig-1R and aggravated ERS in astrocytes, resulting in synapse deficits. PRE-084, a high-affinity and selective Sig-1R agonist, inhibited astrocytic ERS and complement cascades and restored synaptic damage, while the Sig-1R antagonist displayed the opposite results. Moreover, C3a receptor antagonist (C3aRA) could mimic the effect of PRE-084 and exerted neuroprotective effects. In vivo, PRE-084 substantially reduced ER-mitochondrion contact, activation of ERS, and C3/C3a secretion in mice with T1DM. Additionally, the synaptic loss and neurobehavioral dysfunction of mice with T1DM were less pronounced in both the PRE-084 and C3aRA treatment groups. These findings demonstrated that Sig-1R activation reduced the astrocytic ER-mitochondrion contact, ERS activation, and complement-mediated synaptic damage in T1DM. This study suggested the mechanisms and potential therapeutic approaches for treating DACD.

Testosterone has been hypothesized to promote sexual motivation and behavior. However, experimental evidence in healthy humans is sparse and rarely establishes causality. The present study investigated how testosterone affects delay of gratification for sexual rewards. We administered a single dose of testosterone to healthy young males in a double-blind, placebo-controlled, between-participant design (N = 140). Participants underwent a sexual delay discounting task, in which they made a choice between a variable larger-later option (i.e., waiting longer to view a sexual picture for a longer duration) and a smaller-sooner option (i.e., waiting for a fixed shorter period of time to view the same picture for a shorter duration). We found that testosterone administration increased preference for the smaller-sooner option and induced steeper discounting for the delayed option. These findings provide direct experimental evidence that rapid testosterone elevations increase impulsivity for sexual rewards and represent an important step towards a better understanding of the neuroendocrine basis of sexual motivation in humans.

Objective To investigate the effect of brimonidine tartrate 0.2% ophthalmic solution on visual quality after phaco and EDOF IOLs implantation. Methods The prospective non-randomized study comprised 21 eyes of 21 age-related cataract patients who underwent phacoemulsification and EDOF IOLs implantation in the eye center of the Affiliated Hospital of Weifang Medical University from July 2020 to November 2021. The pseudophakic eye was administered topically with bromonidine tartrate 0.2% at 1 month follow up after EDOF IOL implantation. Before and 2 hours,4 hours after brimonidine tartrate drops was administered topically.Under mesopic conditions,OPD-ScanⅢ was used to measure the objective visual quality such as Strehl Ratio (SR),higher order aberrations (HOA),spherical aberration (SA),Coma and Trefoil. The pupil size and palpebral fissure height were evaluated under mesopic conditions. Uncorrected distance visual acuity (UDVA) and the best corrected distance visual acuity (CDVA) were measured using a high-contrast projected logMAR chart. The Visual Functioning-14 (VF-14) scale was used to assess visual functioning and vision-related functional impairment. Results After brimonidine tartrate 0.2% was administered topically,compared to baseline,there were significant differences in ocular HOA,SA and Trefoil, as well as in optical quality parameters (P 0.05).There were significant differences in the mesopic pupil size evaluated after 2 hours and 4 hours brimonidine administration compared to baseline (P 0.05). The VF-14 demonstrated that symptoms of glare or halos can be eliminated after brimonidine administration in 67% in pseudophakic eyes, be alleviated in 24% in pseudophakic eyes and not improved in 9% in pseudophakic eyes. Conclusion Brimonidine tartrate 0.2% ophthalmic solution had an antimydriatic effect under mesopic conditions in the patients with EDOF IOLs implantation. Brimonidine tartrate 0.2% may be used to improve night visual quality in pseudophakic eyes through reducing ocular HOA, SA and Trefoil,increasing SR,and alleviating symptoms of glare or halos in pseudophakic eyes.

The low-temperature growth of materials that support high-performance devices is crucial for advanced semiconductor technologies such as integrated circuits built using monolithic three-dimensional (3D) integration and flexible electronics. However, low growth temperature prohibits sufficient atomic diffusion and directly leads to poor material quality, imposing severe challenges that limit device performance. Here, we demonstrate superior quality growth of 3D semiconductors at growth temperatures reduced by200 °C by using two-dimensional (2D) materials as intermediate layers to optimize the potential energy barrier for adatom diffusion. We reveal the benefits of maintaining, but reducing, the potential field through the 2D layer, which coupled with the inert surface of the 2D material lowers the kinetic barriers, enabling long-distance atomic diffusion and enhanced material quality at lower growth temperatures. As model systems, GaN and ZnSe, grown using WSe

Cardiovascular diseases (CVD) are main public health concerns highly prevalent in industrialized societies where human health is threatened by a series of environmental pollutants, particularly heavy metal contaminants. We aimed to find out if blood heavy metals are associated with the 10-year risk of atherosclerotic cardiovascular disease (ASCVD) in a nationally representative sample of US adults. We analyzed the cross-sectional data on blood heavy metals of 3268 non-Hispanic white participants aged 40-79 years from the National Health and Nutrition Examination Survey (NHANES) 1999-2018. We introduced a risk estimation algorithm, namely the 2013 Pooled Cohort Equations (PCE), to assess the risk for ASCVD over a 10-year period. The 10-year risk for ASCVD was categorized as either reduced risk ( 7.5% risk) or elevated risk (≥ 7.5% risk). Blood lead, cadmium, and mercury were distributed into four quartiles. We used weighted multivariate logistic regression models and restricted cubic spline (RCS) regression to detect the association of blood heavy metal exposure with 10-year ASCVD risk. Following the adjustment of covariates, the adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for elevated 10-year ASCVD risk for participants from the highest quartiles were 4.50 (2.88-7.02), 2.59 (1.68-4.00), and 1.06 (0.66-1.71) for blood cadmium, lead, and mercury compared to the lowest quartiles, respectively. The RCS plot demonstrated that blood cadmium was linearly and positively associated with 10-year ASCVD risk (P for nonlinearity = 0.112). According to our findings, non-Hispanic whites aged 40-79 years had a greater 10-year ASCVD risk as their blood lead and cadmium levels increased. Consequently, when establishing approaches for ASCVD prevention, blood heavy metals should be considered.

Automatic action tendencies occur at behavioral and neurophysiological levels during task performance with the dominant right hand, with shorter reaction times (RTs) and higher excitability of the contralateral primary motor cortex (M1) during automatic vs. regulated behavior. However, effects associated with the non-dominant left-hand in approaching-avoiding behavior remain unclear. Here, we used transcranial magnetic stimulation during the performance by 18 participants of an approaching-avoiding task using the non-dominant left hand. Single-pulse transcranial magnetic stimulation was applied over left or right M1 at 150 and 300 ms after the onset of an emotional stimulus. RTs and motor-evoked potentials (MEPs) were recorded. Significant automatic action tendencies were observed at the behavioral level. Higher MEP amplitudes were detected 150 ms after stimulus onset from the right hand (non-task hand, corresponding to left M1) during regulated behavior compared with during automatic behavior. However, no significant modulation was found for MEP amplitudes from the left hand (task hand, corresponding to right M1). These findings suggested that left M1 may play a principal role in the early phase of mediating left-handed movement toward an emotional stimulus.

Platelets are increasingly recognized as key regulators of inflammatory and immune responses, through their interaction with endothelium and immune cells. Therefore they might have a role in transfusion-related acute lung injury (TRALI), in which endothelial cells and neutrophils are the key players. In this study, by a classic TRALI animal model, combining a custom-designed system for intravital confocal microscopy of pulmonary microvasculature and a platelet tracking technique, we found that thrombin-activated platelets transfusion aggravated TRALI while resting platelets transfusion alleviated TRALI. Promoting endogenous platelets activation also aggravated TRALI while inhibiting endogenous platelets activation alleviated TRALI. Activated platelets interfered with the stability of endothelial barrier function while resting platelets modulated the activation of neutrophils. Anti-thrombin could alleviate TRALI, which was not reproduced upon anti-GPIIbIIIa or anti-P-selectin In conclusion, platelets might play a dual role (protective and pathogenic) in TRALI, the balance between the two roles is highly dependent on whether platelets are activated by thrombin or not. This might explain the conflicting results of previous researches studying the contribution of platelets in TRALI by platelet depletion technology, in which the induction of TRALI and the condition of animals were different, hence the state of platelets during TRALI was different. Moreover, anti-platelet-activation (such as anti-thrombin) might be a better approach than anti-activated-platelets (such as anti-P-selectin) to search for potential therapies in TRALI. Considering the involvement of thrombin-activated platelets in TRALI, anti-thrombin might be needed when blood component transfusion is performed.

The study of moral judgements often centres on moral dilemmas in which options consistent with deontological perspectives (that is, emphasizing rules, individual rights and duties) are in conflict with options consistent with utilitarian judgements (that is, following the greater good based on consequences). Greene et al. (2009) showed that psychological and situational factors (for example, the intent of the agent or the presence of physical contact between the agent and the victim) can play an important role in moral dilemma judgements (for example, the trolley problem). Our knowledge is limited concerning both the universality of these effects outside the United States and the impact of culture on the situational and psychological factors affecting moral judgements. Thus, we empirically tested the universality of the effects of intent and personal force on moral dilemma judgements by replicating the experiments of Greene et al. in 45 countries from all inhabited continents. We found that personal force and its interaction with intention exert influence on moral judgements in the US and Western cultural clusters, replicating and expanding the original findings. Moreover, the personal force effect was present in all cultural clusters, suggesting it is culturally universal. The evidence for the cultural universality of the interaction effect was inconclusive in the Eastern and Southern cultural clusters (depending on exclusion criteria). We found no strong association between collectivism/individualism and moral dilemma judgements. Including participants from 45 countries, Bago et al. find that the situational factors that affect moral reasoning are shared across countries, with diminished observed cultural variation., Comunidad de Madrid [2016-T1/SOC-1395, 2020-5A/SOC-19723]; AEI [PSI2017-85159-P]; UE/FEDER; National Science Centre, Poland [2017/01/X/HS6/01332, 2015/19/D/HS6/00641, 2019/35/B/HS6/00528]; Aarhus University Research Foundation (AUFF) [AUFF-E-2019-9-4]; ANR [ANR-17-EURE-0010]; ANR Labex IAST; Australian Research Council [DP180102384]; CAPES [88887.364180/2019-00]; Carlsberg Foundation [CF16-0444]; Independent Research Fund Denmark [7024-00057B]; Germany's Excellence Strategy [EXC 2126/1-390838866]; FONDECYT, CONICYT [11190980]; German Research Foundation [FOR-2150, LA 3566/1-2]; JSPS [18K03010]; JSPS KAKENHI [16H03079, 17H00875, 18K12015, 20H04581, 17H06342, 20K03479, 20KK0054, 20J21976]; Natural Science Foundation of China (NSFC) [31530032]; Key Technological Projects of Guangdong Province [2018B030335001]; National Science Foundation Graduate Research Fellowship [DGE-1839285]; Polish National Science Center; DFG Beethoven [2016/23/G/HS6/01775]; Portuguese National Foundation for Science and Technology [SFRH/BD/126304/2016, UID/PSI/03125/2019]; PRIN 2017 (Italian Ministry of Education and Research) [20178293XT]; PSA 006 BRA 008 Data Collection in Support of PSADM 001 Measurement Invariance Project; Foundation for Polish Science (START); National Science Centre [2020/36/T/HS6/00256, 2019/33/N/HS6/00054]; Slovak Research and Development Agency [APVV-18-0140, APVV-17-0418, PRIMUS/20/HUM/009, APVV-17-0596]; Social Sciences and Humanities Research Council of Canada [950-224884]; Swedish Research Council [2016-06793]; Project of Philosophy and Social Science Research in Colleges and Universities in Jiangsu Province [2020SJA0017], M.A. Vadillo was supported by 2016-T1/SOC-1395 and 2020-5A/SOC-19723 from Comunidad de Madrid, PSI2017-85159-P from AEI and UE/FEDER. M.P.-C. was supported by 2017/01/X/HS6/01332 from the National Science Centre, Poland. P.M. was supported by Aarhus University Research Foundation (AUFF), starting grant: AUFF-E-2019-9-4. B. Bago was supported by ANR grant ANR-17-EURE-0010 (Investissements d'Avenir programme) and ANR Labex IAST. R.M.R. was supported by the Australian Research Council (DP180102384). N.B.D. was supported by CAPES grant no. 88887.364180/2019-00. C.S., K.A.. and I. Zettler were supported by the Carlsberg Foundation (CF16-0444) and the Independent Research Fund Denmark (7024-00057B). J.L. was supported by EXC 2126/1-390838866 under Germany's Excellence Strategy. K.B. was supported by the following grants from the National Science Centre, Poland: (1) while working on the data collection, no. 2015/19/D/HS6/00641, (2) while working on the final version of the paper, no. 2019/35/B/HS6/00528. A.W. was supported by FONDECYT 11190980, CONICYT. A. Fleischmann was supported by the German Research Foundation (research unit grant FOR-2150, LA 3566/1-2). H.Y. was supported by JSPS grant 18K03010. Y.Y. was supported by JSPS KAKENHI (16H03079, 17H00875, 18K12015 and 20H04581). K.Q. was supported by JSPS KAKENHI (17H06342, 20K03479 and 20KK0054). A. Ikeda was supported by JSPS KAKENHI (20J21976). K.M.K. was supported by National Natural Science Foundation of China (NSFC) grant no. 31530032 and Key Technological Projects of Guangdong Province grant no. 2018B030335001. J.B.C. was supported by National Science Foundation Graduate Research Fellowship grant no. DGE-1839285. M. Parzuchowski, K. Rybus and N.M.S. were supported by Polish National Science Center and DFG Beethoven grant 2016/23/G/HS6/01775. A.C.S. was supported by Portuguese National Foundation for Science and Technology grant no. SFRH/BD/126304/2016. L. Boncinelli was supported by PRIN 2017 grant no. 20178293XT (Italian Ministry of Education and Research). M.F.F.R. was supported by PSA 006 BRA 008 Data Collection in Support of PSADM 001 Measurement Invariance Project. M. Misiak was supported by a scholarship from the Foundation for Polish Science (START) and by a scholarship from the National Science Centre (2020/36/T/HS6/00256). P.B. was supported by Slovak Research and Development Agency project no. APVV-18-0140. M.A. was supported by Slovak Research and Development Agency project no. APVV-17-0418 and project PRIMUS/20/HUM/009. A. Findor and M.H. were supported by the Slovak Research and Development Agency under contract no. APVV-17-0596. T.G. was supported by the Social Sciences and Humanities Research Council of Canada (no. 950-224884). P.P. was supported by the Swedish Research Council (2016-06793). Y.L. was supported by The Project of Philosophy and Social Science Research in Colleges and Universities in Jiangsu Province (grant no. 2020SJA0017). M. Kowal was supported by a scholarship from the National Science Centre (2019/33/N/HS6/00054). P.A. was supported by UID/PSI/03125/2019 from the Portuguese National Foundation for Science and Technology. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

High-altitude polycythemia (HAPC) is characterized by excessive proliferation of erythrocytes, resulting from the hypobaric hypoxia condition in high altitude. The genetic variants and molecular mechanisms of HAPC remain unclear in highlanders. We recruited 141 Tibetan dwellers, including 70 HAPC patients and 71 healthy controls, to detect the possible genetic variants associated with the disease; and performed targeted sequencing on 529 genes associated with the oxygen metabolism and erythrocyte regulation, utilized unconditional logistic regression analysis and GO (gene ontology) analysis to investigate the genetic variations of HAPC. We identified 12 single nucleotide variants, harbored in 12 genes, associated with the risk of HAPC (4.7 ≤ odd ratios ≤ 13.6; 7.6E − 08 ≤ p-value ≤ 1E − 04). The pathway enrichment study of these genes indicated the three pathways, the PI3K-AKT pathway, JAK-STAT pathway, and HIF-1 pathway, are essential, which p-values as 3.70E − 08, 1.28 E − 07, and 3.98 E − 06, respectively. We are hopeful that our results will provide a reference for the etiology research of HAPC. However, additional genetic risk factors and functional investigations are necessary to confirm our results further.

Complementopathy, endotheliopathy, and coagulopathy following a traumatic injury are key pathophysiological mechanisms potentially associated with multiple-organ failure (MOF) and mortality. However, the heterogeneity in the responses of complementopathy, endotheliopathy, and coagulopathy to trauma, the nature and extent of their interplay, and their relationship to clinical outcomes remain unclear. Fifty-four poly-trauma patients were enrolled and divided into three subgroups based on their ISS. Biomarkers in blood plasma reflecting complement activation, endothelial damage, and coagulopathy were measured starting from admission to the emergency department and at 3, 6, 12, 24, and 120 hours after admission. Comparative analyses showed that severely injured patients (ISS>24) were associated with longer days on mechanical ventilation, in the intensive care unit and hospital stays, and a higher incidence of hyperglycemia, bacteremia, respiratory failure and pneumonia compared to mildly (ISS1.57 μg/ml, syndecan-1 >66.6 ng/ml or D-dimer >6 mg/L at admission were associated with a higher risk of MOF/mortality. After adjusting for ISS, each increase of the triadic score defined above (Bb>1.57 µg/ml/Syndecan-1>66.6 ng/ml/D-dimer>6.0mg/L) was associated with a 6-fold higher in the odds ratio of MOF/death [OR: 6.83 (1.04-44.96, P=0.046], and a 4-fold greater in the odds of infectious complications [OR: 4.12 (1.04-16.36), P=0.044]. These findings provide preliminary evidence of two human injury response endotypes (traumatized triad and non-traumatized triad) that align with clinical trajectory, suggesting a potential endotype defined by a high triadic score. Patients with this endotype may be considered for timely intervention to create a pro-survival/organ-protective phenotype and improve clinical outcomes.

International audience; The menopause transition arises mainly from a decline in ovarian function characterized by a decrease in levels of ovarian estrogens (estradiol) and progesterone in women. Menopausal hormone therapy (MHT) has been used to counteract menopause-associated symptoms in postmenopausal women. With the development of advanced brain imaging methods, understanding MHT-related effects on brain structures and functions could help advance our understanding of the biological consequence of MHT-related effects on behavior, thereby contributing to developing new strategies for optimizing brain health during the menopause transition. This review focuses on the human research related to the impact of MHT on structural and functional organization of the prefrontal cortex in postmenopausal women. Although such MHT-related effects on brain structures and functions have only begun to be understood, it may be useful to examine present findings to identify areas for future research.

Propofol and dexmedetomidine are popular used for sedation in ICU, however, inadequate attention has been paid to their effect on gastrointestinal tract (GIT) motility. Present study aimed to compare the effect of propofol and dexmedetomidine on GIT motility at parallel level of sedation and explore the possible mechanism. Male C57BL/6 mice (8–10 weeks) were randomly divided into control, propofol and dexmedetomidine group. After intraperitoneal injection of propofol or dexmedetomidine, comparable sedative level was confirmed by sedative score, physiological parameters and electroencephalogram (EEG). Different segments of GIT motility in vivo (gastric emptying, small intestine transit, distal colon bead expulsion, stool weight and number of fecal pellets, gastrointestinal transit and whole gut transit time) and colonic migrating motor complexes (CMMCs) pattern in vitro were evaluated. The Ca2+ response of primary enteric glia was examined under the treatment of propofol or dexmedetomidine. There is little difference in physiological parameters and composite permutation entropy index (CPEI) between administration of 50 mg/kg propofol and 40 μg/kg dexmedetomidine, indicated that parallel level of sedation was reached. Data showed that propofol and dexmedetomidine had significantly inhibitory effect on GIT motility while dexmedetomidine was stronger. Also, the amplitude (ΔF/F0) of Ca2+ response in primary enteric glia was attenuated after treated with the sedatives while the effect of dexmedetomidine was greater than propofol. These findings demonstrated that dexmedetomidine caused stronger inhibitory effects on GIT motility in sedative mice, which may involve impaired Ca2+ response in enteric glia. Hence, dexmedetomidine should be carefully applied especially for potential GIT dysmotility patient.