A resorcinarene for inhibition of Aβ fibrillation.

Amyloid-β peptides (Aβ) fibrillation is the hallmark of Alzheimer's disease (AD). However, it has been challenging to discover potent agents in order to inhibit Aβ fibrillation. Herein, we demonstrated the effect of resorcinarene on inhibiting Aβ fibrillation in vitro via experimental and computational methods. Aβ were incubated with different concentrations of resorcinarene so as to monitor the kinetics by using thioflavin T binding assay. The results, which were further confirmed by far-UV CD spectroscopy and atomic force microscopy, strongly indicated that the higher concentration of resorcinarene, the more effective the inhibition of Aβ fibrillation. A cytotoxicity study showed that when sea urchin embryos were exposed to the resorcinarene, the majority survived due to the resorcinarene low toxicity. In addition, when the resorcinarene was added, the formation of toxic Aβ 42 species was delayed. Computational studies of Aβ fibrillation, including docking simulations and MD simulations, illustrated that the interaction between inhibitor resorcinarene and Aβ is driven by the non-polar interactions. These studies display a novel strategy for the exploration of promising antiamyloiddogenic agents for AD treatments

Preparation and emulsifying properties of trace elements fortified gum arabic

Gum arabic was enriched with trace elements (Zn2+, Fe3+, Fe2+) by ion exchange against ZnCl2, FeCl3 and FeCl2. Trace elements content, molecular parameters and emulsifying properties of the gum arabic rich in trace elements (GARTE) were characterized by flame atomic absorption spectrometry (FAAS), gel permeation chromatography-multi angle laser light scattering (GPC-MALLS), interfacial rheometer, laser particle analyzer and zeta potentiometry. With trace elements, molecular weight and arabinogalactan protein (AGP) content of gum arabic have increased probably due to the high surface energy leading to the aggregation of protein. GARTE has good emulsion stability performance with increasing molecular weight and AGP content compared to the control gum arabic. GARTE can be applied as a natural functional ingredient for trace element fortification, where the ferric ions and zinc ions are chelated by the self-assembled polymer host

Effect of arabinogalactan protein complex content on emulsification performance of gum arabic

The emulsification properties of the standard (STD), matured (EM2 and EM10) and fractionated gum arabic samples via phase separation induced molecular fractionation were investigated to find out how the content of arabinogalactan protein (AGP) complex affects the resulting emulsion properties. Phase separation and the accompanying molecular fractionation were induced by mixing with different hydrocolloids including hyaluronan (HA), carboxymethyl cellulose (CMC), and maltodextrin (MD). Increase of AGP content from 11 to 28% resulted in the formation of emulsions with relatively smaller droplet sizes and better stability. Further increase in the AGP content to 41% resulted in the formation of emulsions with larger droplets. In spite of the larger droplets sizes, these emulsions were extremely stable. In addition, the emulsions prepared with GA higher AGP content better stability in the presence of ethanol. The results indicate that AGP content plays a vital role in emulsion stability and droplet size

The Local Brain Abnormalities in Patients With Transient Ischemic Attack: A Resting-State fMRI Study

Background: Transient ischemic attack (TIA) is an important risk factor for stroke. Despite the transient episodes of clinical symptoms, brain alterations are still observed in patients with TIA. However, the functional mechanism of transient ischemia is still unclear. Here, we employed resting-state functional magnetic resonance imaging (rs-fMRI) to explore the functional abnormalities in patients with TIA.Methods: 48 TIA patients and 41 age- and sex-matched healthy controls (HCs) were enrolled in the study. For each participant, we collected rs-fMRI data and clinical/physiological/biochemical data. Amplitude of low frequency fluctuation (ALFF), regional homogeneity (ReHo), and degree centrality (DC) were then calculated. Two sample t-tests were performed to compare the ALFF, ReHo, and DC maps between the two groups. Furthermore, a correlation analysis was performed to explore the relationship between local brain abnormalities and clinical/physiological/biochemical characteristics tests in TIA patients.Results: Compared with the HCs, the TIA patients exhibited decreased ALFF in the left middle temporal gyrus, decreased DC in the triangular part of right inferior frontal gyrus, and no significant statistical difference in ReHo. No correlation was found between local abnormalities and clinical/physiological/biochemical scores in the patients with TIA.Conclusion: Collectively, we found decreased ALFF and DC in patients with TIA which provide evidence for local brain dysfunctions and may help to understand the pathological mechanism for the disease

Small Language Model Meets with Reinforced Vision Vocabulary

Playing Large Vision Language Models (LVLMs) in 2023 is trendy among the AI community. However, the relatively large number of parameters (more than 7B) of popular LVLMs makes it difficult to train and deploy on consumer GPUs, discouraging many researchers with limited resources. Imagine how cool it would be to experience all the features of current LVLMs on an old GTX1080ti (our only game card). Accordingly, we present Vary-toy in this report, a small-size Vary along with Qwen-1.8B as the base ``large'' language model. In Vary-toy, we introduce an improved vision vocabulary, allowing the model to not only possess all features of Vary but also gather more generality. Specifically, we replace negative samples of natural images with positive sample data driven by object detection in the procedure of generating vision vocabulary, more sufficiently utilizing the capacity of the vocabulary network and enabling it to efficiently encode visual information corresponding to natural objects. For experiments, Vary-toy can achieve 65.6% ANLS on DocVQA, 59.1% accuracy on ChartQA, 88.1% accuracy on RefCOCO, and 29% on MMVet. The code will be publicly available on the homepage

Effectiveness of resistance training in modulating inflammatory biomarkers among Asian patients with sarcopenia: a systematic review and meta-analysis of randomized controlled trials

ObjectiveGiven the high incidence of sarcopenia among Asians, it is imperative to identify appropriate intervention methods. The International Clinical Practice Guidelines for Sarcopenia, developed by the International Conference on Sarcopenia and Frailty Research (ICFSR) task force, recommends resistance training (RT) as a primary treatment for managing sarcopenia. Inflammatory biomarkers serve as indicators of sarcopenia. However, there is currently insufficient conclusive evidence regarding the effectiveness of RT in modulating inflammatory biomarker levels among Asian participants with sarcopenia.Data sourcesFour databases were utilized for this study until October 9, 2023. This study focused on randomized controlled trials (RCTs) that examined the effects of RT on interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and interleukin-10 (IL-10) about sarcopenia. This study has been registered in the PROSPERO database (CRD42024501855).ResultsThe meta-analysis included six studies from Asians involving 278 participants. The results showed a significant decrease in RT for IL-6 (weighted mean difference (WMD) = -0.73, 95% confidence interval (CI) = -1.02 to -0.44; n=5). However, no significant differences were found for TNF-α (WMD = -1.00, 95% CI = -2.47 to 0.46; n=5), CRP (WMD = -0.45, 95% CI = -1.14 to 0.23; n=3), and IL-10 (WMD = 0.13, 95% CI = -3.99 to 4.25; n=2). Subgroup analysis revealed that factors including gender selection, intervention methods, frequency, period, and duration could have a particular effect on the part of inflammatory biomarkers.ConclusionRT has been shown to reduce part of the level of inflammatory markers, specifically IL-6, in Asian sarcopenia participants. However, other inflammatory factors, such as TNF-α, CRP, and IL-10, did not show significant changes. Further research should confirm the impact of RT on these indicators and explore the potential effects of various factors on different inflammatory markers, such as diet, body composition, and medications.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=501855, identifier CRD42024501855

Small RNA zippers lock miRNA molecules and block miRNA function in mammalian cells.

MicroRNAs (miRNAs) loss-of-function phenotypes are mainly induced by chemically modified antisense oligonucleotides. Here we develop an alternative inhibitor for miRNAs, termed \u27small RNA zipper\u27. It is designed to connect miRNA molecules end to end, forming a DNA-RNA duplex through a complementary interaction with high affinity, high specificity and high stability. Two miRNAs, miR-221 and miR-17, are tested in human breast cancer cell lines, demonstrating the 70∼90% knockdown of miRNA levels by 30-50 nM small RNA zippers. The miR-221 zipper shows capability in rescuing the expression of target genes of miR-221 and reversing the oncogenic function of miR-221 in breast cancer cells. In addition, we demonstrate that the miR-221 zipper attenuates doxorubicin resistance with higher efficiency than anti-miR-221 in human breast cancer cells. Taken together, small RNA zippers are a miRNA inhibitor, which can be used to induce miRNA loss-of-function phenotypes and validate miRNA target genes

Quality Improvement to Increase Breastfeeding in Preterm Infants: Systematic Review and Meta-Analysis

Background and Objective: Due to its numerous health benefits, breast milk (BM) is recommended for preterm infants. Despite such recommendations, the rates of breastfeeding in preterm infants are lower than that in term infants. Quality improvement (QI) bundles increase breastfeeding in preterm infants, but their replication in neonatal intensive care units has had inconsistent outcomes.Methods: We used the Population or Problem, Intervention, Comparison, and Outcomes (PICO) framework to develop our search strategy, and searched MEDLINE, Embase, and the Cochrane Library from inception through January 15, 2021. Studies describing any active QI intervention to increase BM use in preterm infants were included. The primary outcome measure was the rate of any breastfeeding or exclusive mother's own milk (MOM) at discharge or during hospitalization.Results: Sixteen studies were eligible for inclusion and showed an acceptable risk of bias, and included 1 interrupted time series, study 3 controlled before-and-after studies, and 12 uncontrolled before-and-after studies; of these, 3 studies were excluded due to insufficient dichotomous data, 13 were included in the meta-analysis. In the meta-analysis, the rate of any breastfeeding was significantly improved at discharge and during hospitalization after QI [risk ratio (RR) = 1.23, 95% confidence interval (CI): 1.14–1.32, P < 0.00001 and RR = 1.89, 95% CI: 1.09–3.29, P = 0.02, respectively]. The rate of exclusive MOM after QI was also significantly increased at discharge (RR = 1.51, 95% CI: 1.04–2.18, P = 0.03), but not during hospitalization (RR = 1.53, 95% CI: 0.78–2.98, P = 0.22). However, after sensitivity analysis, the comprehensive results still suggested that QI could significantly improve the rate of exclusive MOM during hospitalization (RR = 1.21, 95% CI: 1.08–1.35, P = 0.001). Funnel plots and Egger's test indicated publication bias in the rate of any BF at discharge. We corrected publication bias by trim and fill analysis, and corrected RR to 1.272, 95% CI: (1.175, 1.369), which was consistent with the results of the initial model.Conclusions: A QI bundle appears to be effective for promoting BM use in preterm infants at discharge or during hospitalization