Miracle-dz/UniFAR-FTUs huggingface dataset:
Dynamic Regulation of the Molecular Mechanisms of Regulatory T Cell Migration in Inflamed Skin

The presence of regulatory T cells (Tregs) in skin is important in controlling inflammatory responses in this peripheral tissue. Uninflamed skin contains a population of relatively immotile Tregs often located in clusters around hair follicles. Inflammation induces a significant increase both in the abundance of Tregs within the dermis, and in the proportion of Tregs that are highly migratory. The molecular mechanisms underpinning Treg migration in the dermis are unclear. In this study we used multiphoton intravital microscopy to examine the role of RGD-binding integrins and signalling through phosphoinositide 3-kinase P110δ (PI3K p110δ) in intradermal Treg migration in resting and inflamed skin. We found that inflammation induced Treg migration was dependent on RGD-binding integrins in a context-dependent manner. αv integrin was important for Treg migration 24 hours after induction of inflammation, but contributed to Treg retention at 48 hours, while β1 integrin played a role in Treg retention at the later time point but not during the peak of inflammation. In contrast, inhibition of signalling through PI3K p110δ reduced Treg migration throughout the entire inflammatory response, and also in the absence of inflammation. Together these observations demonstrate that the molecular mechanisms controlling intradermal Treg migration vary markedly according to the phase of the inflammatory response.
Of Time Gals and Mega Men: Empirical Findings on Gender Differences in Digital Game Genre Preferences and the Accuracy of Respective Gender Stereotypes

We investigated the accuracy of gender stereotypes regarding digital game genre preferences. In Study 1, 484 female and male participants rated their preference for 17 game genres (gender differences). In Study 2, another sample of 226 participants rated the extent to which the same genres were presumably preferred by women or men (gender stereotypes). We then compared the results of both studies in order to determine the accuracy of the gender stereotypes. Study 1 revealed actual gender differences for most genres—mostly of moderate size. Study 2 revealed substantial gender stereotypes about genre preferences. When comparing the results from both studies, we found that gender stereotypes were accurate in direction for most genres. However, they were, to some degree, inaccurate in size: For most genres, gender stereotypes overestimated the actual gender difference with a moderate mean effect size.
Racial Ingroup Bias and Efficiency Consideration Influence Distributive Decisions: A Dynamic Analysis of Time Domain and Time Frequency

Although previous studies have demonstrated that identity had effect on justice norms and behavioral decisions, the neural mechanism of that effect remains unclear. In this study, the subjects made their distributive decisions on the trade-off between equity and efficiency among Chinese and foreign children and their scalp potentials were recorded. Behavioral results showed that efficiency consideration played an important part in the distribution task. Meanwhile, participants gave preferential treatment to same-race children. Relative to the distribution within ingroup children, the distribution involving outgroup children induced higher N170 amplitude. The distribution involving outgroup children also elicited weakened P300 amplitude and enhanced delta response than the distribution within ingroup children when subjects are facing the conflict between equality and efficiency. In other words, ingroup bias affected the neural process of the trade-off between equality and efficiency. The combination of time-domain and time-frequency analyses provided spatiotemporal and spectral results for a better understanding of racial ingroup favoritism on distributive justice.
Molecular Mechanics Study of Flow and Surface Influence in Ligand–Protein Association

Ligand–protein association is the first and critical step for many biological and chemical processes. This study investigated the molecular association processes under different environments. In biology, cells have different compartments where ligand–protein binding may occur on a membrane. In experiments involving ligand–protein binding, such as the surface plasmon resonance and continuous flow biosynthesis, a substrate flow and surface are required in experimental settings. As compared with a simple binding condition, which includes only the ligand, protein, and solvent, the association rate and processes may be affected by additional ligand transporting forces and other intermolecular interactions between the ligand and environmental objects. We evaluated these environmental factors by using a ligand xk263 binding to HIV protease (HIVp) with atomistic details. Using Brownian dynamics simulations, we modeled xk263 and HIVp association time and probability when a system has xk263 diffusion flux and a non-polar self-assembled monolayer surface. We also examined different protein orientations and accessible surfaces for xk263. To allow xk263 to access to the dimer interface of immobilized HIVp, we simulated the system by placing the protein 20Å above the surface because immobilizing HIVp on a surface prevented xk263 from contacting with the interface. The non-specific interactions increased the binding probability while the association time remained unchanged. When the xk263 diffusion flux increased, the effective xk263 concentration around HIVp, xk263–HIVp association time and binding probability decreased non-linearly regardless of interacting with the self-assembled monolayer surface or not. The work sheds light on the effects of the solvent flow and surface environment on ligand–protein associations and provides a perspective on experimental design.
Does Chronic Intestinal Inflammation Promote Atrial Fibrillation: A Mendelian Randomization Study With Populations of European Ancestry

Background: Inflammatory bowel disease (IBD), comprising ulcerative colitis (UC), and Crohn's disease (CD), has been reported to be associated with an increased risk of atrial fibrillation (AF). However, the causal role of the chronic intestinal inflammation (CII) in the development of AF remains controversial. We use Mendelian randomization (MR) analysis to explore the causal inference of CII on AF. Methods: A two-sample MR analysis was performed to estimate the potential causal effect of CII on AF. Statistical summaries for the associations between single nucleotide polymorphisms (SNPs) and phenotypes of CII were obtained from genome-wide association studies (GWAS) with cohorts of CD (n = 51,874), UC (n = 47,745), and IBD (n = 65,642) of European descent. The GWAS of 1,030,836 people of European ancestry, including 60,620 AF cases and 970,216 controls was collected to identify genetic variants underlying AF. The causal inference was estimated using the multiplicative random effects inverse-variance weighted method (IVW). The methods of MR-Egger, simple median, and weighted median were also employed to avoid the bias of pleiotropy effects. Results: Using three sets of SNPs (75 SNPs of CD, 60 SNPs of UC, and 95 SNPs of IBD), multiplicative random-effect IVW model estimated a universal null effect of CII on AF (CD: OR = 1.0059, 95% CI: 0.9900, 1.0220, p = 0.47; UC: OR = 1.0087, 95% CI: 0.9896, 1.0281, p = 0.38; IBD: OR = 1.0080, 95% CI: 0.9908, 1.0255, p = 0.37). Similar results were observed using the MR-Egger, simple median, weighted median methods. Conclusion: As opposing to the traditional observational studies, our two-sample MR analysis did not find enough evidence to support a causal role of either CD or UC in the development of AF.
Circulating Proprotein Convertase Subtilisin/Kexin Type 9 Levels and Cardiometabolic Risk Factors: A Population-Based Cohort Study

Aims: To evaluate the prospective association of circulating PCSK9 levels with the cardiometabolic risk profiles (high LDL-cholesterol, high triglycerides, low HDL-cholesterol, hypertension, type 2 diabetes, and metabolic syndrome). Methods: A population-based prospective study was conducted among 7,104 Chinese individuals (age 56.2 ± 7.5 years; 32.0% men). Circulating PCSK9 levels were measured using ELISA. Results: Circulating PCSK9 levels were higher in women than men (286.7 ± 90.1 vs. 276.1 ± 86.4 ng/ml, p < 0.001). And circulating PCSK9 was positively correlated with LDL-cholesterol, total cholesterol, and triglycerides both in men and women (all p < 0.001). The positive correlation between PCSK9 and waist circumference, fasting glucose, insulin resistance, systolic blood pressure, diastolic blood pressure and C-reactive protein (all p < 0.01) was observed in women only. According to Cox regression analysis, circulating PCSK9 was positively associated with incidence of high LDL-cholesterol both in men (HR 1.33, 95% CI 1.09–1.65, p < 0.001) and women (HR 1.36, 95% CI 1.12–1.69, p < 0.001). Moreover, PCSK9 was significantly associated with incident high triglycerides (HR 1.31, 95% CI 1.13–1.72, p < 0.001), hypertension (HR 1.28, 95% CI 1.08–1.53, p = 0.011), type 2 diabetes (HR 1.34, 95% CI 1.09–1.76, p = 0.005), and metabolic syndrome (HR 1.30, 95% CI 1.11–1.65, p = 0.009) per SD change in women only. No statistically significant association was observed between circulating PCSK9 and incidence of low HDL-cholesterol (p > 0.1). Conclusions: Elevated circulating PCSK9 was significantly associated with cardiometabolic risk factors and independently contributed to the prediction of cardiometabolic risks in women.
Resilience as the Mediating Factor in the Relationship Between Sleep Disturbance and Post-stroke Depression of Stroke Patients in China: A Structural Equation Modeling Analysis

Background: Stroke patients may suffer from a variety of symptoms which can result in sleep disturbance and post-stroke depression (PSD). Whereas, resilience can alleviate sleep disturbance and help maintain well-being after stroke. Objective: The aim of this study is to explore whether resilience plays a mediating role in the relationship between sleep disturbance and PSD of stroke patients in China. Methods: A cross-sectional study with a multi-stage sampling was carried out in Liaoning Rehabilitation Center and the Third People's Hospital of Chongqing in China from May to September 2019. A total of 353 stroke patients were enrolled in this study. Structural equation model (SEM) was used to test the mediating effect of resilience on the relationship between sleep disturbance and PSD. Results: The prevalence of PSD of stroke patients was 34.56%. Sleep disturbance contributed most to the variance of PSD and had a significantly positive association with PSD among stroke patients (P < 0.01). Resilience was negatively associated with PSD, and acted as a mediator between sleep disturbance and PSD (a * b = 0.201, BCa 95% CI: 0.156~0.254). Conclusions: The prevalence of PSD was high among the Chinese stroke patients. Sleep disturbance was highly associated with PSD, resulting in the increased risk of PSD. Furthermore, resilience has a mediating effect on the relationship between sleep disturbance and PSD, and could reduce the negative effect of sleep disturbance on the development of PSD.
Effects of Psychosomatic Mutual Aid Treatment on Anxiety and Depression in Turner Syndrome

Background: Turner syndrome (TS) affects approximately one out of 2,500 females. Previous research indicates that girls with TS experience psychosocial impairment in addition to their physical health issues. However, there is no current data demonstrating whether reducing the clinical symptoms of girls or women with TS through hormone replacement therapy (HRT) combined with psychological interventions, referred to as psychosomatic mutual aid treatment (PMAT), improves physical and psychological self-identification, so that psychological problems such as anxiety, depression, low self-esteem, social loneliness, and psychological resilience are improved. Therefore, the objective of this research was to assess the efficacy of PMAT on anxiety and depression in girls and women with TS. Methods: Twenty-six girls and women with TS aged 11–29 years (17.5 ± 4.2 years) were recruited. Anxiety and depression were assessed using Hamilton Anxiety Rating Scale (HAMA) and Zung Self-Rating Depression Scale (SDS) questionnaires, respectively. The 26 TS patients were surveyed for anxiety and depression before the beginning of PMAT and again in January 2020. In addition, 20 healthy volunteer women aged 16–39 years (23.1 ± 5.7 years) were selected as the control group and filled in the questionnaire. Results: Pre-therapy (pre-HRT and Pre-PMAT) there were significant differences between the TS patients (n = 26) and healthy controls (n = 20). In particular, the TS patients had higher anxiety status (P = 0.04) and severity (P = 0.03) (HAMA score), as well as depression status (P = 0.002) and severity (P < 0.001) (SDS score). Post-therapy there was no longer any difference in depression scores, but TS patients still had higher levels of anxiety post-therapy compared with healthy control women (psychic symptoms score, P = 0.03; anxiety status score, P = 0.04; anxiety severity score, P = 0.04). In the TS patients, there was an improvement in depression scores (SDS score P < 0.001; depression severity score, P = 0.005) after therapy but no change in levels of anxiety. Conclusions: PMAT significantly improves depression status, but not anxiety, in girls and women with TS. Clinical Trial Registration: http://www.chictr. org.cn/showproj.aspx? proj=124736, identifier: ChiCTR2100045230.
Combining 68Ga-PSMA-PET/CT-Directed and Elective Radiation Therapy Improves Outcome in Oligorecurrent Prostate Cancer: A Retrospective Multicenter Study

Background In case of oligo-recurrent prostate cancer (PC) following prostatectomy, 68Ga-PSMA-PET/CT can be used to detect a specific site of recurrence and to initiate metastasis-directed radiation therapy (MDT). However, large heterogeneities exist concerning doses, treatment fields and radiation techniques, with some studies reporting focal radiotherapy (RT) to PSMA-PET/CT positive lesions only and other studies using elective RT strategies. We aimed to compare oncological outcomes and toxicity between PET/CT-directed RT (PDRT) and PDRT plus elective RT (eRT; i.e. prostate bed, pelvic or paraaortal nodes) in a large retrospective multicenter study. Methods Data of 394 patients with oligo-recurrent 68Ga-PSMA-PET/CT-positive PC treated between 04/2013 and 01/2018 in six different academic institutions were evaluated. Primary endpoint was biochemical-recurrence-free survival (bRFS). bRFS was analyzed using Kaplan–Meier survival curves and log rank testing. Uni- and multivariate analyses were performed to determine influence of treatment parameters. Results In 204 patients (51.8%) RT was directed only to lesions seen on 68Ga-PSMA-PET/CT (PDRT), 190 patients (48.2%) received PDRT plus eRT. PDRT plus eRT was associated with a significantly improved 3-year bRFS compared to PDRT alone (53 vs. 37%; p = 0.001) and remained an independent factor in multivariate analysis (p = 0.006, HR 0.29, 95% CI 0.12–0.68). This effect was more pronounced in the subgroup of patients who were treated with PDRT and elective prostate bed radiotherapy (ePBRT) with a 3-year bRFS of 61% versus 22% (p <0.001). Acute and late toxicity grade ≥3 was 0.8% and 3% after PDRT plus eRT versus no toxicity grade ≥3 after PDRT alone. Conclusions In this large cohort of patients with oligo-recurrent prostate cancer, elective irradiation of the pelvic lymphatics and the prostatic bed significantly improved bRFS when added to 68Ga-PSMA-PET/CT-guided focal radiotherapy. These findings need to be evaluated in a randomized controlled trial.
A NIST Kinetic Data Base for PAH Reaction and Soot Particle Inception During Combusion

Abstract : A gas-phase chemical kinetics database was developed that describes the transformation of fuel molecules to their desired end products of carbon dioxide and water, as well as to the undesired polycyclic aromatic hydrocarbons (PAH), and a quantitative soot particle inception model based on experiments was developed. Surrogate real fuel molecules studied included heptane as a representative of the aliphatic constituents of real fuel and butylbenzene as a representative of the aromatic component. Existing data was compiled, evaluated and updated using NIST CHEMRATE, a user friendly reaction rate theory program, to determine which kinetic rates would be measured. Rates for fuel cracking and reactions involving PAH with three or fewer rings using a shock tube were identified. A particle inception model was developed based on experiments performed in diffusion flames and in a well-stirred reactor.
Spatial Distribution and Provenance of Detrital Minerals of Surface Sediment in the Okhotsk Sea

The Okhotsk Sea is a distinctive marginal sea in the northwestern Pacific Ocean, which is characterized by the prevalence of seasonal sea ice in winter. Sediment is sourced from the around region through sea ice transportation, rivers input, and volcanic eruptions. Surface sediments of the Okhotsk Sea shelf vary greatly in grain size, and the sand content is generally high, which is conducive to source-to-sink studies using ice-rafted detritus (IRD),detrital minerals and single mineral geochemistry methods. In this paper, the 63–125 μm grain size fraction was selected for the detrital minerals analysis of surface sediments (top 0–10 cm) from 58 sediment stations and 15 stations samples has been chosen for garnet chemistry. These stations are mainly located in the south central Okhotsk Sea. The distribution and composition of the heavy minerals are influenced by material derived from the Amur River, the north shelf (Okhotsk-Chukotka volcanic belt), Sakhalin Island, the Kamchatka Peninsula, and the Kuril Islands. The detrital mineral results show that hornblende, epidote and garnet are terrigenous material indicators. High contents of fresh hypersthene can be used as an indicator of volcanic eruption materials. And high content of abraded hypersthene can be used as an indicator of Okhotsk-Chukotka volcanic materials. In the northern Okhotsk Sea, the southward moving sea ice produced in Sakhalin Bay collides with the sea ice produced off the east coast of Sakhalin Island, which causes the sea ice to accumulate to the southeast. This results in the deposited ice-rafted debris having a southeastward facing fan shape, and the geochemical analysis of the garnet supports this conclusion. From west to east, the amount of material from Sakhalin Island gradually decreases, while the amount of material from the Amur River and Chukchi-Kamchatka increases.
The Characteristics, Prevalence, and Risk Factors of Drug-Induced Liver Injury Among Brucellosis Inpatients in Xinjiang, China

Background: We investigated the prevalence, demographic and clinical features, and risk factors associated with drug-induced liver injury (DILI) during the treatment of brucellosis inpatients in a retrospective study. Methods: We collected the clinical data of 782 brucellosis inpatients admitted at the Shawan County People’s Hospital, Xinjiang, from 2015–2019. All cases were re-evaluated using the international consensus of DILI criteria and RUCAM rating scale. 71 patients were confirmed as DILI cases and compared with 523 other patients with normal liver function. Results: It was indicated that DILI occurred with a prevalence of about 9.08% among brucellosis inpatients receiving drug therapy. Hepatocellular injury was the most common type of DILI (61.97%, 95% confidence interval [CI] 50.34–72.37), followed by mixed (23.94%, 95% CI 15.52–35.04) and cholestatic types (14.08%, 95% CI 7.83–24.02). In addition, 13.64% of the hepatocellular DILI cases fulfilled Hy’s law criteria and only two cases (2.82%) progressed to severe DILI. Most patients adopted the combination of rifampicin, antipyretic analgesics, anti-infective agents, and traditional Chinese medicine for the treatment of brucellosis, with all the 71 patients taking rifampicin as the drug of choice. Multivariable logistic regression analyses indicated that obesity, regular alcohol intake, and decreased serum albumin were the independent risk factors of DILI in patients with brucellosis after adjusting for gender, age, and ethnicity. Conclusion: DILI occurred in a minority of inpatients diagnosed with brucellosis receiving rifampicin-based therapeutic regimen. In addition, obesity, alcohol abuse, and decreased serum albumin were valuable predictors of the risk of DILI in patients with brucellosis.
Born With Bristles: New Insights on the Kölliker’s Organs of Octopus Skin

The entire skin surface of octopus embryos, hatchlings and juveniles bears scattered tufts of tiny chitinous setae within small pockets, from which they can be everted and retracted. Known as Kölliker’s organs (KO), they disappear before the subadult stage. The function of these structures during the early life of the octopus is unknown, despite having been first described nearly two centuries ago. To investigate these organs further, general trends in size of KO distribution and density were analyzed in hatchlings and juveniles of 17 octopod species from all oceans, representing holobenthic, holopelagic and meropelagic modes of life. The size of the KO is fairly constant across species, unrelated to mode of life or hatchling size. The density of KO is similar on ventral and dorsal body surfaces, but hatchlings of smaller size tend to have a higher density of KO on the aboral surface of the arms. Analysis of a series of post-hatching Octopus vulgaris shows KO size to be constant throughout ontogeny; it is therefore a consistent structure during the octopus early life from planktonic hatchling to benthic juvenile. New KO are generated on the skin of the arm tips during the planktonic period and initial benthic lives of juveniles. Their density, on both the mantle and arms, gradually decreases as the octopus grows. In older benthic juveniles, the KO degrades, losing its setae and the base of its follicle becomes exposed as a nearly circular stump of muscle. It is estimated that fully everted KO increase the body surface area by around two-thirds compared to when the KO are retracted. This modular mechanism of body surface extension and roughness probably influences flow-related forces such as drag and propulsion of the moving surface of the young octopus while it is of small size with a relatively large surface area. In addition, the distribution of these organs on the aboral surface of the arms of the octopus and their birefringent properties suggest a role in camouflage. Further research is needed to test these hypotheses of KO function in live animals.
Investigating the Mechanism of Sodium Binding to SERT Using Direct Simulations

The serotonin transporter (SERT) terminates neurotransmission by transporting serotonin from the synapse into the pre-synaptic nerve terminal. Altered SERT function leads to several neurological diseases including depression, anxiety, mood disorders, and attention deficit hyperactivity disorders (ADHD). Accordingly SERT is the target for their pharmacological treatments, but also targeted by multiple drugs of abuse. Transport of serotonin by SERT is energized by the transmembrane electrochemical gradient of sodium. We used extensive molecular dynamics simulations to investigate the process of sodium binding to SERT, which is the first step in the transport cycle that leads to serotonin uptake. Comparing data from 51 independent simulations, we find a remarkably well-defined path for sodium entry and could identify two transient binding sites, while observing binding kinetics that are comparable to experimental data. Importantly, the structure and dynamics of the sodium binding sites indicate that sodium binding is accompanied by an induced-fit mechanism that leads to new conformations and reduces local dynamics.