Miracle-dz/UniFAR-FTUs huggingface dataset:
Endocytosis gated by emergent properties of membrane-clathrin interactions

Clathrin-mediated endocytosis (CME), the major cellular entry pathway, starts when clathrin assembles on the plasma membrane into clathrin-coated pits (CCPs). Two populations of CCPs are detected within the same cell: ‘productive’ CCPs that invaginate and pinch off, forming clathrin-coated vesicles (CCVs) [1, 2], and ‘abortive’ CCPs [3, 4, 5] that prematurely disassemble. The mechanisms of gating between these two populations and their relations to the functions of dozens of early-acting endocytic accessory proteins (EAPs) [5, 6, 7, 8, 9] have remained elusive. Here, we use experimentally-guided modeling to integrate the clathrin machinery and membrane mechanics in a single dynamical system. We show that the split between the two populations is an emergent property of this system, in which a switch between an Open state and a Closed state follows from the competition between the chemical energy of the clathrin basket and the mechanical energy of membrane bending. In silico experiments revealed an abrupt transition between the two states that acutely depends on the strength of the clathrin basket. This critical strength is lowered by membrane-bending EAPs [10, 11, 12]. Thus, CME is poised to be shifted between abortive and productive events by small changes in membrane curvature and/or coat stability. This model clarifies the workings of a putative endocytic checkpoint whose existence was previously proposed based on statistical analyses of the lifetime distributions of CCPs [4, 13]. Overall, a mechanistic framework is established to elucidate the diverse and redundant functions of EAPs in regulating CME progression.
EXTRACELLULAR CIRP INHIBITS NEUTROPHIL APOPTOSIS TO PROMOTE ITS AGING BY UPREGULATING SERPINB2 IN SEPSIS

ABSTRACT Background: Sepsis reduces neutrophil apoptosis. As the result, neutrophils may become aged, exacerbating inflammation and tissue injury. Extracellular cold-inducible RNA-binding protein (eCIRP) acts as a damage-associated molecular pattern to promote inflammation and tissue injury in sepsis. SerpinB2, a serine protease inhibitor, has been shown to inhibit apoptosis. We hypothesize that eCIRP upregulates SerpinB2 to promote aged neutrophil subset by inhibiting apoptosis in sepsis. Methods: We stimulated bone marrow–derived neutrophils (BMDNs) of wild-type (WT) mice with 1 μg/mL of recombinant mouse CIRP (i.e., eCIRP) and assessed cleaved caspase-3 and SerpinB2 by western blotting. Apoptotic neutrophils were assessed by Annexin V/PI. Bone marrow–derived neutrophils were stimulated with 1 μg/mL eCIRP and treated with or without PAC-1 (caspase-3 activator) and aged neutrophils (CXCR4hiCD62Llo) were assessed by flow cytometry. To induce sepsis, we performed cecal ligation and puncture in WT or CIRP−/− mice. We determined the percentage of aged neutrophils and SerpinB2+ neutrophils in blood and spleen by flow cytometry. Results: We found that cleaved caspase-3 levels were increased at 4 h of PBS treatment compared with 0 h but decreased by eCIRP treatment. Extracellular cold-inducible RNA-binding protein reduced apoptotic cells after 20 h of treatment. Extracellular cold-inducible RNA-binding protein also increased the frequencies of aged neutrophils compared with PBS after 20 h, while PAC-1 treatment reduced aging in eCIRP-treated BMDNs. Extracellular cold-inducible RNA-binding protein significantly increased the expression of SerpinB2 at protein levels in BMDNs at 20 h. In WT mice, the frequencies of aged and SerpinB2+ neutrophils in blood and spleen were increased after 20 h of cecal ligation and puncture, while in CIRP−/− mice, aged and SerpinB2+ neutrophils were significantly decreased compared with WT mice. We also found that aged neutrophils expressed significantly higher levels of SerpinB2 compared with non-aged neutrophils. Conclusions: eCIRP inhibits neutrophil apoptosis to increase aged phenotype by increasing SerpinB2 expression in sepsis. Thus, targeting eCIRP could be a new therapeutic strategy to ameliorate inflammation caused by neutrophil aging in sepsis.
Effects of interpreting a dynamic geometric cue as gaze on attention allocation

Gaze is a powerful cue for directing attention. We investigate the interpretation of an abstract figure as gaze modulates its efficacy as an attentional cue. In each trial, two vertical lines on a central disk moved to one side (left or right). Independent of this “feature-cued” side, a target (black disk) subsequently appeared on one side. After 300 trials (phase 1), participants watched a video of a human avatar walking away. For one group, the avatar wore a helmet that visually matched the central disk and looked at black disks to either side. The other group's video was unrelated to the cueing task. After another 300 trials (phase 2), videos were swapped between groups; 300 further trials (phase 3) followed. In all phases, participants responded more quickly for targets appearing on the feature-cued side. There was a significant interaction between group and phase for reaction times: In phase 3, the group who had just watched the avatar with the helmet had a reduced advantage to the feature-cued side. Hence, interpreting the disk as a turning head seen from behind counteracts the cueing by the motion of the disk. This suggests that the mere perceptual interpretation of an abstract stimulus as gaze yields social cueing effects.
Full‐thickness skin rejuvenation by a novel dual‐length microneedle radiofrequency device: A proof‐of‐concept study using human skin

A novel dual‐length microneedle radiofrequency (DLMR) device has been developed to achieve full‐thickness skin rejuvenation by stimulating the papillary and reticular dermis simultaneously. This device's dual‐level targeting concept need to be validated on human skin, although its clinical efficacy has been demonstrated in a previous study.
Disclosing an autism diagnosis: A social identity approach

Autistic people face a difficult dilemma around whether or not to disclose their diagnosis because autistic people are a stigmatized social group. The central aim of this study was to examine if a social identity approach could be useful in understanding the factors that predict the likelihood of autistic adults disclosing their autism diagnosis in social settings, in the workplace, in educational settings and in the family. The social identity approach predicts that autistic people may cope with this dilemma by using an individualistic strategy to distance themselves from their autistic social identity. Alternatively, they may embrace their autistic social identity and use a collective strategy to resist stigma and advocate for autistic people. We present a survey based cross‐sectional study (n = 175) with autistic adults living in Ireland. Participants completed a series of measures; autism social identification, stigma consciousness, and individualistic and collective strategy use to assess disclosing in the four settings. The overall models in each of the four regressions were significant. Autism social identification positively predicted disclosure in social, workplace and educational settings, while stigma consciousness negatively predicted disclosure in the family and in the workplace. Interestingly, over and above these predictors individualistic strategy use negatively predicted disclosure in each of the four settings, while collective strategy use positively predicted disclosure in social, educational and family settings. Our novel social identity approach was useful for explaining autistic adults' strategies to cope with the complex disclosure dilemma. Strengths, limitations, and directions for future research are discussed.
Exploration of mRNA nanoparticles based on DOTAP through optimization of the helper lipids

Lipid nanoparticles (LNPs) are one of the most efficient carriers for RNA packaging and delivery, and vaccines based on mRNA‐LNPs have received substantial attention since the outbreak of the COVID‐19 pandemic. LNPs based on 1,2‐dioleoyl‐3‐trimethylammonium propane (DOTAP) have been widely used in preclinical and clinical settings. A novel non‐viral gene delivery system called LNP3 was previously developed, which was composed of DOTAP, 1,2‐dioleoyl‐sn‐glycero‐3‐phosphoethanolamine (DOPE), and cholesterol. One of the helper lipids in this carrier was DOPE, which belongs to phospholipids. Given that substituting DOPE with non‐phospholipids as helper lipids can increase the delivery efficiency of some LNPs, this study aimed to examine whether non‐phospholipids can be formulated with DOTAP as helper lipids. It was found that monoglycerides with C14:0, C16:0, C18:0, C18:1, and C18:2 mediated mRNA transfection, and the transfection efficiency varied between C18:0, C18:1, and C18:2. Furthermore, substituting of the glycerol with other moieties such as the cholesterol or the ethanolamine similarly mediated mRNA transfection. The introduction of cholesterol can further improve the transfection capacity of some DOTAP‐based LNPs. One of the best‐performing formulations, LNP3‐MO, was used to mediate luciferase‐mRNA expression in vivo, and the luminescence signal was found to be mainly enriched in the lung and spleen. In addition, the level of SARS‐CoV‐2 spike antibody in the serum increased after three doses of LNP3‐MO mediated SARS‐CoV‐2 spike mRNA. Altogether, this study demonstrates that non‐phospholipids are promising helper lipids that can be formulated with DOTAP to facilitate efficient delivery of mRNAs in vitro and in vivo with organ‐specific targeting.
CangFu Daotan decoction improves polycystic ovarian syndrome by downregulating FOXK1

Abstract Objective: Polycystic ovarian syndrome (PCOS) is a prevalent gynecologic disorder, often associated with abnormal follicular development. Cangfu Daotan decoction (CFD) is a traditional Chinese medicine formula that is effective in alleviating PCOS clinically, but the specific mechanism remains unclear. Forkhead box K1 (FOXK1) is associated with cellular function. This study aimed to explore the effects of CFD and FOXK1 on PCOS.Methods: High-fat diet and letrozole were combined to establish PCOS rat models. Next, primary GCs were extracted from those PCOS rats. Then, GC cells were transfected with si-FOXK1 or oe-FOXK1. CFD-contain serum was prepared, and experiments were conducted to investigate the regulation of FOXK1 by CFD.Results: FOXK1 was highly expressed in GCs of PCOS rats. Further investigation revealed that FOXK1 overexpression resulted in inhibition of proliferation and DNA synthesis, along with promotion of apoptosis and autophagy in GCs. Additionally, it was found that FOXK1 promoted the expressions of the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway-related proteins. Interestingly, treatment with CFD reversed all the effects of FOXK1 overexpression in GCs. Conclusion: This study demonstrated that CFD exerted a protective role in PCOS by inhibiting FOXK1, which provided a research basis for the application of CFD in PCOS, and suggested that FOXK1 is a novel therapeutic target in PCOS treatment.
Association with controlling nutritional status score and disease activity of ulcerative colitis

Objective To explore the association between the controlling nutritional status (CONUT) score and disease activity in patients with ulcerative colitis (UC). Methods This retrospective study enrolled patients with UC. Demographic, clinical and laboratory data were collected and compared. The CONUT score was obtained for each patient. The association between the CONUT score and laboratory parameters was analysed and the ability of the score to assess disease activity was evaluated. Results A total of 182 patients with UC were enrolled. Patients with active disease showed significantly increased inflammatory biomarkers and decreased nutritional biomarkers compared with patients in remission. Malnourished individuals had significantly elevated inflammatory biomarkers and significantly reduced haemoglobin, prealbumin and retinol-binding protein. The CONUT score was inversely correlated with haemoglobin, prealbumin, retinol-binding protein and was positively correlated with faecal calprotectin, C-reactive protein, erythrocyte sedimentation rate, neutrophil/lymphocyte ratio and platelet/lymphocyte ratio. The area under the receiver operating characteristic curve was 0.655 (95% confidence interval, 0.557–0.752). The optimal cut-off value was 1.5 points, with a sensitivity of 75.7% and a specificity of 50.0%. Conclusion The CONUT score may evaluate the inflammatory response and nutritional status of UC patients, so it could be a potential biomarker to assess disease activity in UC.
Vagal Nerve Therapy in the Management of Obesity: A Systematic Review and Meta-Analysis

Introduction: The vagus nerve has an important role in satiety, metabolism, and autonomic control in upper gastrointestinal function. However, the role and effects of vagal nerve therapy on weight loss remain controversial. This systematic review and meta-analysis assessed the effects of vagal nerve therapy on weight loss, body mass index (BMI), and obesity-related conditions. Methods: MEDLINE, EMBASE, and CINAHL databases were searched for studies up to April 2022 that reported on percentage excess weight loss (%EWL) or BMI at 12 months or remission of obesity-related conditions following vagal nerve therapy from January 2000 to April 2022. Weighted mean difference (WMD) was calculated, meta-analysis was performed using random-effects models, and between-study heterogeneity was assessed. Results: Fifteen studies, of which nine were randomised controlled trials, of 1,447 patients were included. Vagal nerve therapy led to some improvement in %EWL (WMD 17.19%; 95% confidence interval [CI]: 10.94–23.44; p < 0.001) and BMI (WMD −2.24 kg/m2; 95% CI: −4.07 to −0.42; p = 0.016). There was a general improvement found in HbA1c following vagal nerve therapy when compared to no treatment given. No major complications were reported. Conclusions: Vagal nerve therapy can safely result in a mild-to-moderate improvement in weight loss. However, further clinical trials are required to confirm these results and investigate the possibility of the long-term benefit of vagal nerve therapy as a dual therapy combined with standard surgical bariatric interventions.
Superconductivity near the Mott-Ioffe-Regel limit in the high-entropy alloy superconductor 
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Theoretical analysis of the electronic structure of the high-entropy-type superconductor (ScZrNb)$_{1-x}$(RhPd)$_x$, $x \in (0.35, 0.45)$ is presented. The studied material is a partially ordered CsCl-type structure, with two sublattices, randomly occupied by Sc, Zr, Nb (first sublattice) and Nb, Rh, and Pd (second sublattice). Calculations were done using the Korringa-Kohn-Rostoker method with the coherent potential approximation (KKR-CPA) and take into account the substitutional disorder. Our total energy calculations confirm the preference for the partially ordered structure over the fully random {\it bcc}-type one. Electronic densities of states $N(E)$, dispersion relations, and McMillan-Hopfield parameters $\eta$ (electronic contribution to electron-phonon coupling) are studied as a function of composition. The computed increasing trends in $N(E_F)$ and $\eta$ with $x$ are opposite to what we expected based on the experimental results, where the decrease in the critical temperature with increasing $x$ was found. Very strong electron scattering due to disorder is observed, as the electronic dispersion relations are strongly smeared. As a result, the computed electronic lifetimes $\tau$ are very short, leading to a small mean-free path of electrons of the order of interatomic distance, which puts (ScZrNb)$_{1-x}$(RhPd)$_x$ near the Mott-Ioffe-Regel limit. The trend in $\tau(x)$ is similar to the trend observed experimentally in $T_c(x)$, suggesting that disorder may be the factor that influences $T_c$ in this series of alloys.
Accelerated and Quantitative 3D Semisolid MT/CEST Imaging using a Generative Adversarial Network (GAN-CEST)

Purpose: To substantially shorten the acquisition time required for quantitative 3D chemical exchange saturation transfer (CEST) and semisolid magnetization transfer (MT) imaging and allow for rapid chemical exchange parameter map reconstruction. Methods: Three-dimensional CEST and MT magnetic resonance ﬁngerprinting (MRF) datasets of L-arginine phantoms, whole-brains, and calf muscles from healthy volunteers, cancer patients, and cardiac patients were acquired using 3T clinical scanners at 3 different sites, using 3 different scanner models and coils. A generative adversarial network supervised framework (GAN-CEST) was then designed and trained to learn the mapping from a reduced input data space to the quantitative exchange parameter space, while preserving perceptual and quantitative content. Results: The GAN-CEST 3D acquisition time was 42-52 seconds, 70% shorter than CEST-MRF. The quantitative reconstruction of the entire brain took 0.8 seconds. An excellent agreement was observed between the ground truth and GAN-based L-arginine concentration and pH values (Pearson's r > 0.97, NRMSE < 1.5%). GAN-CEST images from a brain-tumor subject yielded a semi-solid volume fraction and exchange rate NRMSE of 3.8 ± 1.3% and 4.6±1.3%, respectively, and SSIM of 96.3±1.6% and 95.0±2.4%, respectively. The mapping of the calf-muscle exchange parameters in a cardiac patient, yielded NRMSE < 7% and SSIM > 94% for the semi-solid exchange parameters. In regions with large susceptibility artifacts, GAN-CEST has demonstrated improved performance and reduced noise compared to MRF. Conclusion: GAN-CEST can substantially reduce the acquisition time for quantitative semisolid MT/CEST mapping, while retaining performance even when facing pathologies and scanner models that were not available during training.
Revisiting the rationale of mandatory masking

In this perspective, we review the evidence for the efficacy of face masks to reduce the transmission of respiratory viruses, specifically severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and consider the value of mandating universal mask wearing against the widespread negative impacts that have been associated with such measures. Before the SARS-CoV-2 pandemic, it was considered that there was little to no benefit in healthy people wearing masks as prophylaxis against becoming infected or as unwitting vectors of viral transmission. This accepted policy was hastily reversed early on in the pandemic, when districts and countries throughout the world imposed stringent masking mandates. Now, more than three years since the start of the pandemic, the amassed studies that have investigated the use of masks to reduce transmission of SARS-CoV-2 (or other pathogens) have led to conclusions that are largely inconsistent and contradictory. There is no statistically significant or unambiguous scientific evidence to justify mandatory masking for general, healthy populations with the intention of lessening the viral spread. Even if mask wearing could potentially reduce the transmission of SARS-CoV-2 in individual cases, this needs to be balanced against the physical, psychological and social harms associated with forced mask wearing, not to mention the negative impact of innumerable disposed masks entering our fragile environment. Given the lack of unequivocal scientific proof that masks have any effect on reducing transmission, together with the evident harms to people and the environment through the use of masks, it is our opinion that the mandatory use of face masks in the general population is unjustifiable and must be abandoned in future pandemic countermeasures policies.
dPASP: A Comprehensive Differentiable Probabilistic Answer Set Programming Environment For Neurosymbolic Learning and Reasoning

We present dPASP, a novel declarative probabilistic logic programming framework for differentiable neuro-symbolic reasoning. The framework allows for the specification of discrete probabilistic models with neural predicates, logic constraints and interval-valued probabilistic choices, thus supporting models that combine low-level perception (images, texts, etc), common-sense reasoning, and (vague) statistical knowledge. To support all such features, we discuss the several semantics for probabilistic logic programs that can express nondeterministic, contradictory, incomplete and/or statistical knowledge. We also discuss how gradient-based learning can be performed with neural predicates and probabilistic choices under selected semantics. We then describe an implemented package that supports inference and learning in the language, along with several example programs. The package requires minimal user knowledge of deep learning system's inner workings, while allowing end-to-end training of rather sophisticated models and loss functions.
An integrative analytical framework to identify healthy, impactful, and equitable foods: a case study on 100% orange juice

Abstract To identify healthy, impactful, and equitable foods, we combined health scores from six diverse nutrient profiling systems (NPS) into a meta-framework (meta-NPS) and paired this with dietary guideline adherence assessment via multilevel regression and poststratification. In a case-study format, a commonly debated beverage formulation – 100% orange juice (OJ) – was chosen to showcase the utility and depth of our framework, systematically scoring high across multiple food systems (i.e. a Meta-Score percentile = 93rd and Stability percentile = 75th) and leading to an expected increase of US dietary fruit guideline adherence by ∼10%. Moreover, the increased adherence varies across the 300 sociodemographic strata, with the benefit patterns being sensitive to absolute or relative quantification of the difference of adherence affected by OJ. In sum, the adaptable, integrative framework we established deepens the science of nutrient profiling and dietary guideline adherence assessment while shedding light on the nuances of defining equitable health effects. Graphical abstract We developed a meta-nutrient profiling system (meta-NPS) to establish a consensus healthfulness evaluation and paired these assessments with quantification of dietary impact and equity. Integrating individual NPS, the meta-NPS has two novel features – Meta Score (the average rank) and Stability (the relative rank certainty), shown via empirical cumulative distribution function curves. In terms of impact and equity, multiple modelling approaches were utilised to estimate fruit guideline adherence impacted by orange juice for 300 subpopulations. While the framework applies to any food, 100% orange juice was highlighted to advertise salient utility.