Miracle-dz/UniFAR-FTUs huggingface dataset:
Improved Antitumor Efficacy of Combined Vaccine Based on the Induced HUVECs and DC-CT26 Against Colorectal Carcinoma

Angiogenesis is essential for the development, growth, and metastasis of solid tumors. Vaccination with viable human umbilical vein endothelial cells (HUVECs) has been used for antitumor angiogenesis. However, the limited immune response induced by HUVECs hinders their clinical application. In the present study, we found that HUVECs induced by a tumor microenvironment using the supernatant of murine CT26 colorectal cancer cells exerted a better antiangiogenic effect than HUVECs themselves. The inhibitory effect on tumor growth in the induced HUVEC group was significantly better than that of the HUVEC group, and the induced HUVEC group showed a strong inhibition in CD31-positive microvessel density in the tumor tissues. Moreover, the level of anti-induced HUVEC membrane protein antibody in mouse serum was profoundly higher in the induced HUVEC group than in the HUVEC group. Based on this, the antitumor effect of a vaccine with a combination of induced HUVECs and dendritic cell-loading CT26 antigen (DC-CT26) was evaluated. Notably, the microvessel density of tumor specimens was significantly lower in the combined vaccine group than in the control groups. Furthermore, the spleen index, the killing effect of cytotoxic T lymphocytes (CTLs), and the concentration of interferon-γ in the serum were enhanced in the combined vaccine group. Based on these results, the combined vaccine targeting both tumor angiogenesis and tumor cells may be an attractive and effective cancer immunotherapy strategy.
Fexofenadine and Rosuvastatin Pharmacokinetics in Mice with Targeted Disruption of Organic Anion Transporting Polypeptide 2B1

Organic anion transporting polypeptide 2B1 (OATP2B1) is a widely expressed membrane transporter with diverse substrate specificity. In vitro and clinical studies suggest a role for intestinal OATP2B1 in the oral absorption of medications. Moreover, OATP2B1 is highly expressed in hepatocytes where it is thought to promote liver drug clearance. However, until now, a shortcoming of studies implicating OATP2B1 in drug disposition has been a lack of in vivo models. Here, we report the development of a knockout (KO) mouse model with targeted, global disruption of the Slco2b1 gene to examine the disposition of two confirmed mOATP2B1 substrates, namely, fexofenadine and rosuvastatin. The plasma pharmacokinetics of intravenously administered fexofenadine was not different between KO and wild-type (WT) mice. However, after oral fexofenadine administration, KO mice had 70% and 41% lower maximal plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC0–last) than WT mice, respectively. In WT mice, coadministration of fexofenadine with grapefruit juice (GFJ) or apple juice (AJ) was associated with reduced Cmax by 80% and 88%, respectively, while the AUC0–last values were lower by 35% and 70%, respectively. In KO mice, AJ coadministration reduced oral fexofenadine Cmax and AUC0–last values by 67% and 59%, respectively, while GFJ had no effects. Intravenous and oral rosuvastatin pharmacokinetics were similar among WT and KO mice. We conclude that intestinal OATP2B1 is a determinant of oral fexofenadine absorption, as well as a target for fruit juice interactions. OATP2B1 does not significantly influence rosuvastatin disposition in mice. Significance Statement A novel mouse model with targeted disruption of the Slco2b1 gene revealed that OATP2B1 is a determinant of oral absorption but not systemic disposition of fexofenadine, as well as a target of fruit juice interactions. Rosuvastatin oral and intravenous pharmacokinetics were not dependent on OATP2B1. These findings support the utility of the Slco2b1 KO mouse model for defining mechanisms of drug disposition at the intersection of in vitro and clinical pharmacology.
Quercetin protect cigarette smoke extracts induced inflammation and apoptosis in RPE cells

Abstract Background Age-related macular degeneration (AMD) is the leading cause of blindness in elderly population in the developed world. Dysfunction of retinal pigment epithelium (RPE) likely triggers early AMD stages. The effect of Quercetin on the early AMD in-vitro model remained unclear. Methods The effect of Quercetin in the cell viability was detected with CCK8 methods in control, CSE treated, and CSE with Quercetin treatment group. The apoptotic status in each group was detected with tunnel assay. The oxidative and inflammation biomarkers were detected by ELISA. The expression levels of Keap1/Nrf2/ARE in RPE cells were measured by western blot after pretreatment of Quercetin followed by CSE treatment. Results It was found that Quercetin could improve the cell viability and decrease cellular apoptotic rate in the CSE treated RPE group. The expressions of inflammatory and apoptotic biomarkers were significantly decreased in Quercetin treatment group. Furthermore, Quercetin exerts protective effects via activation Keap1/Nrf2/ARE pathway in CSE treated RPE cells. Conclusions Quercetin demonstrated significant protective effects in an in-vitro model of early AMD and it might be a new therapeutic strategy for the management of early AMD.
Tryptophan-related dipeptides in fermented dairy products suppress microglial activation and prevent cognitive decline

The rapid growth in aging populations has made prevention of age-related memory decline and dementia a high priority. Several epidemiological and clinical studies have concluded that fermented dairy products can help prevent cognitive decline; furthermore, intake of Camembert cheese prevents microglial inflammation and Alzheimer’s pathology in mouse models. To elucidate the molecular mechanisms underlying the preventive effects of fermented dairy products, we screened peptides from digested milk protein for their potential to regulate the activation of microglia. We identified dipeptides of tryptophan–tyrosine (WY) and tryptophan–methionine that suppressed the microglial inflammatory response and enhanced the phagocytosis of amyloid-β (Aβ). Various fermented dairy products and food materials contain the WY peptide. Orally administered WY peptide was smoothly absorbed into blood, delivered to the brain, and improved the cognitive decline induced by lipopolysaccharide via the suppression of inflammation. Intake of the WY peptide prevented microglial inflammation, hippocampal long-term potential deficit, and memory impairment in aged mice. In an Alzheimer’s model using 5×FAD mice, intake of the WY peptide also suppressed microglial inflammation and accumulation of Aβ, which improved cognitive decline. The identified dipeptides regulating microglial activity could potentially be used to prevent cognitive decline and dementia related to inflammation.
Association of high birth weight with overweight and obesity in Chinese students aged 6–18 years: a national, cross-sectional study in China

Background The prevalence of childhood overweight and obesity in China has drastically increased 57 times over the past 30 years, and to control birth weight is an effective way to reduce the risk of overweight and obesity across the life course. Objective This paper aimed to evaluate the association of high birth weight (HBW) with overweight and obesity in Chinese students aged 6–18 years. Methods All students with HBW (n=4981) aged 6–18 years were selected from a cross-sectional survey from seven provinces of China, and 4981 other students with normal birth weight (NBW) were randomly sampled with matched gender, age and province. Anthropometric parameters were measured and characteristics were collected by questionnaires. Multiple logistic regression was used to estimate the OR of overweight and obesity with HBW, unadjusted and adjusted for confounding factors. Results Participants with HBW revealed higher body mass index in childhood. The prevalence of overweight and obesity was significantly higher in the HBW group than in the NBW group (overweight 15.3% vs 13.1%, p<0.05; obesity 16.9% vs 10.6%, p<0.05), and the results were similar for overweight in all age groups except age 6–7, age 14–15 and age 16–18. Additionally, HBW was positively associated with overweight (OR=1.230; 95% CI 1.056 to 1.432) and obesity (OR=1.611; 95% CI 1.368 to 1.897) after adjustment for covariates. Conclusions HBW leads to an increased risk of overweight and obesity in childhood; thus, measures to control birth weight, such as controlling gestational weight gain, should be taken from the earliest beginning of life. Trial registration number NCT02343588; Post-results.
Structure from Motion Multisource Application for Landslide Characterization and Monitoring: The Champlas du Col Case Study, Sestriere, North-Western Italy

Structure from Motion (SfM) is a powerful tool to provide 3D point clouds from a sequence of images taken from different remote sensing technologies. The use of this approach for processing images captured from both Remotely Piloted Aerial Vehicles (RPAS), historical aerial photograms, and smartphones, constitutes a valuable solution for the identification and characterization of active landslides. We applied SfM to process all the acquired and available images for the study of the Champlas du Col landslide, a complex slope instability reactivated in spring 2018 in the Piemonte Region (north-western Italy). This last reactivation of the slide, principally due to snow melting at the end of the winter season, interrupted the main road used to reach Sestriere, one of the most famous ski resorts in north-western Italy. We tested how SfM can be applied to process high-resolution multisource datasets by processing: (i) historical aerial photograms collected from five diverse regional flights, (ii) RGB and multi-spectral images acquired by two RPAS, taken in different moments, and (iii) terrestrial sequences of the most representative kinematic elements due to the evolution of the landslide. In addition, we obtained an overall framework of the historical development of the area of interest, and distinguished several generations of landslides. Moreover, an in-depth geomorphological characterization of the Champlas du Col landslide reactivation was done, by testing a cost-effective and rapid methodology based on SfM principles, which is easily repeatable to characterize and investigate active landslides.
Feasibility of GPS-based warning system for roadside workers

Roadside workers and emergency responders, such as police and emergency medical technicians, are at significant risk of being struck by vehicular traffic while performing their duties. While recent work has examined active and passive systems to reduce pedestrian collisions, current approaches require line of sight using either laser, infrared, or vision based systems. We address this problem by developing a GPS-based solution that equips roadside workers and vehicles with GPS units to estimate the trajectory of oncoming traffic, and estimate whether worker strike is imminent. The results of our study show that our approach is 91% accurate in alerting the worker and vehicle of collisions and near misses. Furthermore, accurate warnings can be provided 5-6 seconds before any potential collision, allowing time for mitigating solutions.
Physician-Patient Relations: No More Models

Currently, the common theoretical models of "preferred" decision-making relationships do not correspond well with clinical experience. This interview study of congestive heart failure (CHF) patients documents the variety of patient preferences for decision-making, and the necessity for attention to family involvement. In addition, these findings illustrate the confusion as to the designation of surrogate decision-makers and physicians in charge. We conclude that no single model of physician-patient decision-making should be preferred, and that physicians should first ask patients how they want medical information and decision-making to be handled.
The Transcription Factor INDUCER OF CBF EXPRESSION1 Interacts with ABSCISIC ACID INSENSITIVE5 and DELLA Proteins to Fine-Tune Abscisic Acid Signaling during Seed Germination in Arabidopsis

A transcriptional complex involving ABSCISIC ACID INSENSITIVE5 and its interacting partners maintains the appropriate level of abscisic acid signaling during seed germination. ABSCISIC ACID INSENSITIVE5 (ABI5) is a crucial regulator of abscisic acid (ABA) signaling pathways involved in repressing seed germination and postgerminative growth in Arabidopsis (Arabidopsis thaliana). ABI5 is precisely modulated at the posttranslational level; however, the transcriptional regulatory mechanisms underlying ABI5 and its interacting transcription factors remain largely unknown. Here, we found that INDUCER OF CBF EXPRESSION1 (ICE1) physically associates with ABI5. ICE1 negatively regulates ABA responses during seed germination and directly suppresses ABA-responsive LATE EMBRYOGENESIS ABUNDANT6 (EM6) and EM1 expression. Genetic analysis demonstrated that the ABA-hypersensitive phenotype of the ice1 mutant requires ABI5. ICE1 interferes with the transcriptional activity of ABI5 to mediate downstream regulons. Importantly, ICE1 also interacts with DELLA proteins, which stimulate ABI5 during ABA signaling. Disruption of ICE1 partially restored the ABA-hyposensitive phenotype of the della mutant, gai-t6 rga-t2 rgl1-1 rgl2-1, indicating that ICE1 functions antagonistically with DELLA in ABA signaling. Consistently, DELLA proteins repress ICE1’s transcriptional function and the antagonistic effect of ICE1 on ABI5. Collectively, our study demonstrates that ICE1 antagonizes ABI5 and DELLA activity to maintain the appropriate level of ABA signaling during seed germination, providing a mechanistic understanding of how ABA signaling is fine-tuned by a transcriptional complex involving ABI5 and its interacting partners.
Molecular events occurring behind ultraviolet-induced skin inflammation

We reviewed a recent advance in the studies of the molecular mechanisms for ‘ultraviolet responses’, paying special attention to two transcription factors, nuclear factor kappa B and p53, and to a balance noted between an anti-apoptotic phosphatidylinositol 3-kinase-Akt pathway and its inhibitory ceramide-caveolin-1 pathway. These studies were mostly carried out using in vitro or animal models. On the basis of these results, we determined that phase by phase molecular events clarified in these studies correspond well with the three phases of ultraviolet-induced inflammation observed, i.e. the early vasodilatory phase, the second inflammatory phase in which many inflammatory cells such as neutrophils and T cells accumulate in the skin, and the last regressive phase based on several anti-inflammatory events.
A Stabilizing Model Predictive Control for Linear Systems with Input Saturation

A stabilizing model predictive control (MPC) strategy is proposed for linear systems with input saturation. A saturated linear feedback controller is selected as the local stabilizing controller. The terminal constraint set and terminal cost function can be computed by solving a corresponding semi-definite programming (SDP) problem. Then the control action is obtained by solving a second order cone programming (SOCP) problem on-line. Feasibility of SOCP problem implies the stability of the closed-loop system. Simulation shows that the proposed algorithm has a larger region of attraction than existed stabilizing MPC algorithms
Production, characterization, and in vivo half-life extension of polymeric IgA molecules in mice

ABSTRACT IgA antibodies have broad potential as a novel therapeutic platform based on their superior receptor-mediated cytotoxic activity, potent neutralization of pathogens, and ability to transcytose across mucosal barriers via polymeric immunoglobulin receptor (pIgR)-mediated transport, compared to traditional IgG-based drugs. However, the transition of IgA into clinical development has been challenged by complex expression and characterization, as well as rapid serum clearance that is thought to be mediated by glycan receptor scavenging of recombinantly produced IgA monomer bearing incompletely sialylated N-linked glycans. Here, we present a comprehensive biochemical, biophysical, and structural characterization of recombinantly produced monomeric, dimeric and polymeric human IgA. We further explore two strategies to overcome the rapid serum clearance of polymeric IgA: removal of all N-linked glycosylation sites creating an aglycosylated polymeric IgA and engineering in FcRn binding with the generation of a polymeric IgG-IgA Fc fusion. While previous reports and the results presented in this study indicate that glycan-mediated clearance plays a major role for monomeric IgA, systemic clearance of polymeric IgA in mice is predominantly controlled by mechanisms other than glycan receptor clearance, such as pIgR-mediated transcytosis. The developed IgA platform now provides the potential to specifically target pIgR expressing tissues, while maintaining low systemic exposure.
Geometric morphometric analysis of the effect of temperature on wing size and shape in Aedes albopictus

Wing geometry helps to identify mosquito species, even cryptic ones. On the other hand, temperature has a well‐known effect on insect metric properties. Can such effects blur the taxonomic signal embedded in the wing? Two strains of Aedes albopictus (laboratory and field strain) were examined under three different rearing temperatures (26, 30 and 33 °C) using landmark‐ and outline‐based morphometric approaches. The wings of each experimental line were compared with Aedes aegypti. Both approaches indicated similar associations between wing size and temperature. For the laboratory strain, the wing size significantly decreased as the temperature increased. For the field strain, the largest wings were observed at the intermediate temperature. The two morphometric approaches describing shape showed different sensibilities to temperature. For both strains and sexes, the landmark‐based approach disclosed significant wing shape changes with temperature changes. The outline‐based approach showed lesser effects, detecting significant changes only in laboratory females and in field males. Despite the size and shape changes induced by temperature, the two strains of Ae. albopictus were always distinguished from Ae. aegypti. The present study confirms the lability of size. However, it also suggests that, despite environmentally‐induced variation, the architecture of the wing still provides a strong taxonomic signal.
Analysis of the clinical effect of olfactory training on olfactory dysfunction after upper respiratory tract infection

Abstract Background: Olfactory dysfunction is a common symptom during otolaryngology outpatient service. Objective: To explore the clinical effect of olfactory training on olfactory dysfunction after upper respiratory tract infection (URTI), and its influence factors. Material and methods: A total of 60 confirmed cases of URTI-induced olfactory dysfunction were enrolled into the present study. The olfactory training lasted for 24 weeks. These patients were tested using Sniffin’ Sticks and threshold-discrimination-identification (TDI) composite scoring before treatment, and at 1, 3 and 6 months after treatment. Results: It was found that URTI-induced olfactory dysfunction patients had more evident deterioration in odor identification ability. The effective rates of olfactory training on olfactory dysfunction at 1, 3 and 6 months after treatment were 1.67%, 26.67% and 41.67%, respectively. The TDI scores at the 3rd and 6th months, but not at the 1st month, were significantly higher, when compared to those before treatment. The course of diseases was a significant influence factor on the therapeutic effect of olfactory training (OR = 0.805, 95% CI: 0.696–0.931). Conclusions: Olfactory training can efficiently cure URTI-induced olfactory dysfunction, and in particular, significantly improve the odor discrimination ability and odor identification ability. Significance: Providing useful data for further research regarding olfactory dysfunction.
Synchronization of complex networks of identical and nonidentical chaotic systems via model-matching control

In this work, a synchronization scheme for networks of complex systems is presented. The proposed synchronization scheme uses a control law obtained with some definitions from graph theory and solving the Model-Matching Problem for complex networks. In particular, Rössler, Chen, Lorenz and Lü chaotic systems are used as complex chaotic systems into complex networks. Particular cases with regular and irregular networks of six identical chaotic systems are implemented, with some well-known topologies as star and ring small-world, and tree topologies. Highlighting, the obtained control law is applied to synchronize an irregular network of six different chaotic systems in a tree topology. The usefulness and advantages of the proposed synchronization scheme are highlighted performing numerical simulations of the chaotic complex networks.
Development, Reliability, and Validity of the Multiple Errands Test Home Version (MET-Home) in Adults With Stroke.

OBJECTIVE Our objective was to perform initial psychometric analysis of the Multiple Errands Test Home Version (MET-Home), which was designed to assess the influence of poststroke executive dysfunction on in-home task performance. METHOD We examined the reliability and validity of the MET-Home in adults with stroke (n = 23) and individually matched control participants (n = 23). All participants completed a series of assessments during a single in-home visit. RESULTS Notable differences in MET-Home subscores were discovered between participants with stroke and control participants. Participants with stroke omitted more tasks, broke more rules, passed by tasks more often, and were less efficient than matched control participants. The MET-Home demonstrated evidence of adequate internal consistency, excellent interrater reliability, and significant moderate associations with several tests. CONCLUSION This preliminary study suggests that the MET-Home differentiates between adults with stroke and matched control participants. The MET-Home provides evidence of initial reliability and validity among adults with stroke.
Metamorphic HEMT technology for low-noise applications

Different noise sources in HEMTs are discussed, and state-of-the-art low-noise amplifiers based on the Fraunhofer IAF 100 nm and 50 nm gate length metamorphic HEMT (mHEMT) process are presented. These mHEMT technology feature an extrinsic ƒT of 220 / 375 GHz and an extrinsic transconduction gm, max of 1300 / 1800 mS/mm. By using the 50 nm technology several low-noise amplifier MMICs were realized. A small signal gain of 21 dB and a noise figure of 1.9 dB was measured in the frequency range between 80 and 100 GHz at ambient temperature. To investigate the low temperature behaviour of the 100 nm technology, single 4 * 40 µm mHEMTs were integrated in hybrid 4 – 8 GHz (Chalmers) and 16 – 26 GHz (Yebes) amplifiers. At cryogenic temperatures noise temperatures of 3 K at 5 GHz and 12 K at 22 GHz were achieved.
TRP Channels as Lower Urinary Tract Sensory Targets

Several members of the transient receptor potential (TRP) superfamily, including TRPV1, TRPV2, TRPV4, TRM4, TRPM8 and TRPA1, are expressed in the lower urinary tract (LUT), not only in neuronal fibers innervating the bladder and urethra, but also in the urothelial and muscular layers of the bladder and urethral walls. In the LUT, TRP channels are mainly involved in nociception and mechanosensory transduction. Animal studies have suggested the therapeutic potential of several TRP channels for the treatment of both bladder over- and underactivity and bladder pain disorders,; however translation of this finding to clinical application has been slow and the involvement of these channels in normal human bladder function, and in various pathologic states have not been established. The development of selective TRP channel agonists and antagonists is ongoing and the use of such agents can be expected to offer new and important information concerning both normal physiological functions and possible therapeutic applications.