Miracle-dz/UniFAR-FTUs huggingface dataset:
Endothelial cell‐derived oxysterol ablation attenuates experimental autoimmune encephalomyelitis

The vasculature is a key regulator of leukocyte trafficking into the central nervous system (CNS) during inflammatory diseases including multiple sclerosis (MS). However, the impact of endothelial‐derived factors on CNS immune responses remains unknown. Bioactive lipids, in particular oxysterols downstream of Cholesterol‐25‐hydroxylase (Ch25h), promote neuroinflammation but their functions in the CNS are not well‐understood. Using floxed‐reporter Ch25h knock‐in mice, we trace Ch25h expression to CNS endothelial cells (ECs) and myeloid cells and demonstrate that Ch25h ablation specifically from ECs attenuates experimental autoimmune encephalomyelitis (EAE). Mechanistically, inflamed Ch25h‐deficient CNS ECs display altered lipid metabolism favoring polymorphonuclear myeloid‐derived suppressor cell (PMN‐MDSC) expansion, which suppresses encephalitogenic T lymphocyte proliferation. Additionally, endothelial Ch25h‐deficiency combined with immature neutrophil mobilization into the blood circulation nearly completely protects mice from EAE. Our findings reveal a central role for CNS endothelial Ch25h in promoting neuroinflammation by inhibiting the expansion of immunosuppressive myeloid cell populations.
MODEL FOR ARTIFICIAL NIGHT-SKY ILLUMINATION.

A model has been constructed to allow calculation of the night-sky brightness caused by a city at its center and outside the city, and at arbitrary zenith distances. A circular city of uniform brightness is assumed, with the total brightness proportional to the population. Molecular scattering and aerosol scattering are included, with the amount of aerosols being an adjustable parameter, and different scale heights being adopted for molecules and aerosols. The reflectivity of the ground and the fraction of light radiated above the horizontal are taken as parameters. Applications are given to several cities, to the general population-distance relations, to brightness-distance relations, and to the city center brightness-population relations.
Role of Glucosamine and Chondroitin in the Prevention of Cancer: A Meta-Analysis

Abstract The anti-inflammatory properties of glucosamine and chondroitin suggest that they may have potential effects in cancer prevention. We performed this meta-analysis to assess the protective function of glucosamine and/or chondroitin intake against cancer risk. We searched the PubMed, Embase, Web of Science, and China National Knowledge Infrastructure (CNKI) databases. The odds ratio (OR), corresponding to the 95% confidence interval (95% CI), was used to assess the association between chondroitin and/or glucosamine intake and cancer risk. Thirteen studies met the inclusion criteria, with 1,690,918 participants and 55,045 cancer cases. Overall, chondroitin and/or glucosamine intake was associated with a lower risk of colorectal cancer (OR = 0.91, 95% CI, 0.87–0.94) and lung cancer (OR = 0.84, 95% CI, 0.79–0.89). Subgroup analysis supported the protective effect of different SYSADOAs (chondroitin and/or glucosamine) intake. However, the protective effect was not observed in the only chondroitin intake group and in the NSAIDs group. Our meta-analysis found that the intake of glucosamine and/or chondroitin decreased the risk of colorectal and lung cancers. Moreover, NSAIDs use may have a synergistic protective effect.
Open Surgery for Abdominal Aortic Aneurysm: 980 Consecutive Patient Outcomes from a High-Volume Centre in the United Kingdom

Background Controversy persists regarding the optimal treatment for large abdominal aortic aneurysm (AAA), highlighted by the publication of the National Institute for Health and Care Excellence (NICE) guideline (NG156) on March 2020. The pendulum of opinion swings once more from endovascular to open surgical treatment. We report our experience over the last 15 years in treating consecutive AAA by open surgery. Methods A retrospective review of a prospectively collected vascular database of all patients undergoing infra-renal open abdominal aortic aneurysm repair (OR) repair from 2004 to 2019 at the largest aneurysm centre in the United Kingdom. OR for elective and emergency (ruptured and symptomatic) outcomes included early morbidity and 30-day mortality, and long-term survival. Results 1017 patients underwent OR between 2004-2019, on application of our inclusion-criteria 994 patients formed our cohort for analysis (81.2% male) with a mean age 73.6 ± 7.8 years treated by OR for AAA. In that group 672 were elective and 308 were emergency (for ruptured or symptomatic). Overall 30 day mortality was 11.3%, elective 30 day mortality was 2.5%, and emergency 30 day mortality was 29.9%. 30 day re-intervention rate was 9.5%, (elective 7.0%, emergency 15.9%). Survival at 1000 days for elective repair was 72 v 46.7% for emergency and at 2000 days was 43.4% for elective v 25% for emergency. Conclusion Our data confirm that open surgery for AAA can be performed in large volume centres quite safely. Elective and Emergency surgery does affect early 30 day mortality but does not influence long-term outcome.
Expanded MutaT7 toolkit efficiently and simultaneously accesses all possible transition mutations in bacteria

Abstract Targeted mutagenesis mediated by nucleotide base deaminase–T7 RNA polymerase fusions has recently emerged as a novel and broadly useful strategy to power genetic diversification in the context of in vivo directed evolution campaigns. Here, we expand the utility of this approach by introducing a highly active adenosine deaminase–T7 RNA polymerase fusion protein (eMutaT7A→G), resulting in higher mutation frequencies to enable more rapid directed evolution. We also assess the benefits and potential downsides of using this more active mutator. We go on to show in Escherichia coli that adenosine deaminase-bearing mutators (MutaT7A→G or eMutaT7A→G) can be employed in tandem with a cytidine deaminase-bearing mutator (MutaT7C→T) to introduce all possible transition mutations simultaneously. We illustrate the efficacy of this in vivo mutagenesis approach by exploring mutational routes to antibacterial drug resistance. This work sets the stage for general application of optimized MutaT7 tools able to induce all types of transition mutations during in vivo directed evolution campaigns across diverse organisms.
Effect of Gene 33/Mig6/ERRFI1 on hexavalent chromium-induced transformation of human bronchial epithelial cells depends on the length of exposure

Abstract Hexavalent chromium (Cr(VI)) compounds are environmental and occupational lung carcinogens. The present study followed the chronic effect of Cr(VI) on the neoplastic transformation of BEAS-2B lung bronchial epithelial cells with or without deletion of Gene 33 (Mig6, EFFRI1), a multifunctional adaptor protein. We find that Gene 33-deleted cells exhibit increased anchorage-independent growth compared to control cells after transformed by 8-week but not 24-week Cr(VI) exposure. Gene 33-deleted cells show a higher level of cell proliferation and are more resistant to acute Cr(VI) toxicity compared to control cells after transformed by 8-week but not 24-week Cr(VI) exposure, despite that 24-week-transformed cells have increased resistance to acute Cr(VI) toxicity. However, Gene 33-deleted cells show increased migration after transformed by both 8-week and 24-week Cr(VI) exposures. Furthermore, only cells transformed by 24 weeks of Cr(VI) exposure can form subcutaneous tumors in nude mice. Although no significant difference in the size of tumors formed by the two cell types, there is a marked difference in the histological manifestation and more MMP3 expression in tumors from Gene 33-deleted cells. Our results demonstrate progressive neoplastic transformation of BEAS-2B cells and the adaptation of these cells to Gene 33 deletion during chronic exposure to Cr(VI).
Holding time has limited impact on constitutive innate immune function in a long-lived Antarctic seabird, the Adélie penguin: implications for field studies

ABSTRACT There is great interest in measuring immune function in wild animals. Yet, field conditions often have methodological challenges related to handling stress, which can alter physiology. Despite general consensus that immune function is influenced by handling stress, previous studies have provided equivocal results. Furthermore, few studies have focused on long-lived species, which may have different stress-immune trade-offs compared to short-lived species that have primarily been tested. Here, we investigate whether capture and handling duration impacts innate immune function in a long-lived seabird, the Adélie penguin (Pygoscelis adeliae). We found no evidence for changes in three commonly used parameters of innate immune function upon holding time of up to 2 h, suggesting that immune function in this species is more robust against handling than in other species. This opens up exciting possibilities for measuring immune function in species with similar life-histories even if samples cannot be taken directly after capture.
Caffeine-Supplemented Diet Prevents Fatigue-Like Behavior in Tumor-Bearing Mice

Abstract Caffeine is a widely consumed stimulant, known for its positive effects on physical and mental performance. These effects are potentially beneficial for ameliorating cancer-related fatigue, which affects the quality of life of patients with cancer. This study aimed to determine the anti-fatigue and antitumor effects of caffeine in tumor-bearing mice. BALB/c mice were intravenously injected with C26 colon carcinoma cells and fed with normal or 0.05% caffeine-supplemented diet. Fatigue-like behavior was assessed by running performance using a treadmill test. Lung, blood, liver, muscle, and epididymal adipose tissue samples were collected on day 13 and examined. The antitumor effect of caffeine was assessed using subcutaneous tumor-bearing mice fed with 0.05% caffeine-supplemented diet, and the tumor volume was measured. C26 tumor-bearing mice showed fatigue-like behavior associated with hypoglycemia, depleted liver glycogen and non-esterified fatty acid (NEFA) levels. C26 tumor-bearing mice fed with 0.05% caffeine-supplemented diet showed improved running performance associated with restored NEFA levels. However, exacerbated hypoglycemia and liver glycogen levels after caffeine consumption may be due to tumor-induced catabolic signals, as the tumor volume was not affected. Collectively, caffeine may exert anti-fatigue effects through enhanced lipolysis leading to restored NEFA levels, which can be used as an alternative energy source.
The relevance of familiarity in the context of self-related information processing

Humans are inclined to preferentially process self-related content, referred to as the “self-bias. ” Different paradigms have been used to study this effect. However, not all paradigms included a familiar other condition (but rather an unfamiliar other condition), needed to differentiate self-specific effects from the impact of familiarity. The primary goal of our study was to test the suitability for studying the self-bias of two paradigms that provide robust measures of salience effects—that is, the Repetition Blindness (RB) effect and the Emotional Stroop (ES) interference—while addressing the familiarity confound. We further explored whether self-bias effects were related to autism symptomatology, as a reduced self-bias in autism has been reported in previous research. In an online procedure, 82 adults performed an RB task and an ES task in a counterbalanced order, while being presented with both self- and familiar other-related stimuli. Results of both frequentist and Bayesian analyses did not provide evidence in favour of a specific self-bias on either task: we found no significant modulation of the RB effect, nor of the ES interference, for the own versus a close other’s name. Moreover, no link with autism symptomatology was found. Tackling a crucial shortcoming from earlier studies, our investigation raises awareness on the importance of accounting for familiarity when investigating self-related processing.
Interaction of panel flutter with inviscid boundary layer instability in supersonic flow

Abstract We investigate the stability of an elastic plate in supersonic gas flow. This problem has been studied in many papers regarding panel flutter, where uniform flow is usually considered. In this paper, we take the boundary layer on the plate into account and investigate its influence on plate stability. Three problem formulations are studied. First, we investigate the stability of travelling waves in an infinite-length plate. Second, the nature of the instability (absolute or convective instability) is examined. Finally, by using solutions of the first two problems, instability of a long finite-length plate is studied by using Kulikovskii’s global instability criterion. The following results are obtained. All the eigenmodes of a finite-length plate are split into two types, which we call subsonic and supersonic. The influence of the boundary layer on these eigenmodes can be of two kinds. First, for a generalized convex boundary layer profile (typical for accelerating flow), supersonic eigenmodes are stabilized by the boundary layer, whereas subsonic disturbances are destabilized. Second, for a profile with a generalized inflection point (typical for constant and decelerating flows), supersonic eigenmodes are destabilized in a thin boundary layer and stabilized in a thick layer; subsonic eigenmodes are damped. The correspondence between the influence of the boundary layer on panel flutter and the stability of the boundary layer over a rigid wall is established. Examples of stable boundary layer profiles of both types are given.
Light-sheet microscopy reveals dorsoventral asymmetric membrane dynamics of Amoeba proteus during pressure-driven locomotion

ABSTRACT Amoebae are found all around the world and play an essential role in the carbon cycle in the environment. Therefore, the behavior of amoebae is a crucial factor when considering the global environment. Amoebae change their distribution through amoeboid locomotion, which are classified into several modes. In the pressure-driven mode, intracellular hydrostatic pressure generated by the contraction of cellular cortex actomyosin causes the pseudopod to extend. During amoeboid locomotion, the cellular surface exhibits dynamic deformation. Therefore, to understand the mechanism of amoeboid locomotion, it is important to characterize cellular membrane dynamics. Here, to clarify membrane dynamics during pressure-driven amoeboid locomotion, we developed a polkadot membrane staining method and performed light-sheet microscopy in Amoeba proteus, which exhibits typical pressure-driven amoeboid locomotion. It was observed that the whole cell membrane moved in the direction of movement, and the dorsal cell membrane in the posterior part of the cell moved more slowly than the other membrane. In addition, membrane complexity varied depending on the focused characteristic size of the membrane structure, and in general, the dorsal side was more complex than the ventral side. In summary, the membrane dynamics of Amoeba proteus during pressure-driven locomotion are asymmetric between the dorsal and ventral sides. This article has an associated interview with the co-first authors of the paper.
WY14643 Increases Herpesvirus Replication and Inhibits IFNβ Production Independently of PPARα Expression

PPAR agonists are used clinically to treat both metabolic and inflammatory disorders. Because viruses are known to rewire host metabolism to their own benefit, the intersection of immunity, metabolism, and virology is an important research area. ABSTRACT Peroxisome proliferator activated receptor (PPAR) agonists are commonly used to treat metabolic disorders in humans because they regulate fatty acid oxidation and cholesterol metabolism. In addition to their roles in controlling metabolism, PPAR agonists also regulate inflammation and are immunosuppressive in models of autoimmunity. We aimed to test whether activation of PPARα with clinically relevant ligands could impact gammaherpesvirus infection using murine gammaherpesvirus-68 (MHV68, MuHV-4). We found that PPAR agonists WY14643 and fenofibrate increased herpesvirus replication in vitro. In vivo, WY14643 increased viral replication and caused lethality in mice. Unexpectedly, these effects proved independent of PPARα. We found that WY14643 suppressed production of type I interferon after MHV68 infection in vitro and in vivo. Taken together, our data indicate that caution should be employed when using PPARα agonists in immuno-metabolic studies, as they can have off-target effects on viral replication through the inhibition of type I interferon production. IMPORTANCE PPAR agonists are used clinically to treat both metabolic and inflammatory disorders. Because viruses are known to rewire host metabolism to their own benefit, the intersection of immunity, metabolism, and virology is an important research area. Our article is an important contribution to this field for two reasons. First, it shows a role for PPARα agonists in altering virus replication. Second, it shows that PPARα agonists can affect virus replication in a manner independent of their predicted target. This knowledge is valuable for anyone seeking to use PPARα agonists as a research tool.
Normal range CAG repeat size variations in the HTT gene are associated with an adverse lipoprotein profile partially mediated by body mass index

Abstract Tandem cytosine-adenine-guanine (CAG) repeat sizes of 36 or more in the huntingtin gene (HTT) cause Huntington's disease (HD). Apart from neuropsychiatric complications, the disease is also accompanied by metabolic dysregulation and weight loss, which contribute to a progressive functional decline. Recent studies also reported an association between repeats below the pathogenic threshold (<36) for HD and body mass index (BMI), suggesting that HTT repeat sizes in the non-pathogenic range are associated with metabolic dysregulation. In this study, we hypothesized that HTT repeat sizes < 36 are associated with metabolite levels, possibly mediated through reduced BMI. We pooled data from three European cohorts (n = 10 228) with genotyped HTT CAG repeat size and metabolomic measurements. All 145 metabolites were measured on the same targeted platform in all studies. Multilevel mixed-effects analysis using the CAG repeat size in HTT identified 67 repeat size metabolite associations. Overall, the metabolomic profile associated with larger CAG repeat sizes in HTT were unfavorable—similar to those of higher risk of coronary artery disease and type 2 diabetes—and included elevated levels of amino acids, fatty acids, low-density lipoprotein (LDL)-, very low-density lipoprotein- and intermediate density lipoprotein (IDL)-related metabolites while with decreased levels of very large high-density lipoprotein (HDL)-related metabolites. Furthermore, the associations of 50 metabolites, in particular, specific very large HDL-related metabolites, were mediated by lower BMI. However, no mediation effect was found for 17 metabolites related to LDL and IDL. In conclusion, our findings indicate that large non-pathogenic CAG repeat sizes in HTT are associated with an unfavorable metabolomic profile despite their association with a lower BMI.
Sliding control of non-linear systems containing time-varying uncertainties with unknown bounds

The sliding controller is very effective in dealing with system uncertainties defined in compact sets. If the bounds of the uncertainties are not available, the adaptive sliding controller might be designed. One restriction for the adaptive sliding scheme is that the unknown parameter should be constant, which is not always satisfied in practice. For a non-linear system with general uncertainties (i.e. time varying with unknown bounds), both the traditional sliding control and adaptive sliding control do not work properly. This paper proposes a new sliding control scheme for non-linear systems containing time-varying uncertainties with unknown bounds. The uncertainties are assumed to be piecewise continuous functions of time and satisfy the Dirichlet conditions. By representing these uncertainties in finite-term Fourier series, they can be estimated by updating the Fourier coefficients. Since the coefficients are time-invariant, update laws are easily obtained from the Lyapunov approach to guarantee output error convergence. Computer simulations are performed to show efficacy of the proposed schemes.
Feasibility and Clinical Outcomes of Resuscitative Endovascular Balloon Occlusion of the Aorta in Patients with Traumatic Shock: A Single-Center 5-Year Experience

Background Resuscitative endovascular balloon occlusion of the aorta (REBOA) has recently gained popularity as an adjunct to resuscitation of patients with traumatic shock. However, the effectiveness of REBOA is still debated because of inconsistent indications across centers and the lack of medical records. The purpose of this study was to investigate the effectiveness and feasibility of REBOA by analyzing clinical results from a single center. Methods This study included 96 patients who underwent REBOA between August 2016 and September 2021 at a regional trauma center according to the center’s treatment algorithm for traumatic shock. Medical records, including the time of the decision to conduct the REBOA procedure, time of operation, type of aortic occlusion, and clinical outcomes, were collected prospectively and analyzed retrospectively. Patients were classified by REBOA protocol (group 1, 2, or 3) and survival status (survivor or non-survivor) for analysis. Results The overall success rate of the procedure was 97.9%, and the survival rate was 32.6%. In survivors, blood pressure was higher than in non-survivors both before the REBOA procedure (p=0.002) and after aortic occlusion (p=0.03). The total aortic occlusion time was significantly shorter (p=0.001) and the proportion of partial aortic occlusion was significantly higher (p=0.014) among the survivors. The non-survivors had more acidosis (p<0.001) and higher lactate concentrations (p<0.001) than the survivors. Conclusion REBOA may be a feasible bridge therapy for resuscitation of patients with traumatic shock. Prompt and accurate decision-making to perform REBOA followed by damage control surgery could improve survival rates and clinical outcomes.