Miracle-dz/UniFAR-FTUs huggingface dataset:
Pien-tze-huang promotes wound healing in streptozotocin-induced diabetes models associated with improving oxidative stress via the Nrf2/ARE pathway

Diabetic foot ulcers are a serious complication of diabetes, with high mortality and a lack of effective clinical treatment, which leads to a considerable financial burden. Pien-Tze-Huang (PZH) is a Chinese traditional medicine with a long history that has been found to be an effective and convenient treatment for inflammatory diseases such as skin abscesses and ulcers. In this study, we assessed the effects of PZH on diabetic wounds and the underlying mechanisms. The wounds were established on the backs of streptozotocin-induced type 1 diabetic rats and type 2 diabetic mouse models. We found that PZH treatment used locally or by gavage significantly promoted wound healing, accelerated re-epithelialization and vasculature in the wound tissue, upregulated the expression of the growth factors VEGF-A, PDGF, and EGF, and activated the Nrf2/ARE pathway in the wound tissue. In vitro assays showed that PZH improved the proliferation, migration and angiogenic function of human umbilical vein endothelial cells (HUVECs) cultured in palmitic acid, reduced the expression of the apoptotic proteins p53, Bax, and cleaved-caspase3, and activated Nrf2/ARE signaling; however, these protective effects were abrogated after Nrf2 was knocked down by specific siRNA. In addition, the levels of the serum inflammatory cytokines IL-1β, TNF-α, and IL-6 were reduced after PZH gavage treatment. In conclusion, the positive role of PZH in diabetic wound healing might be related to the activation of the Nrf2/ARE pathway to regulate the level of oxidative stress in vivo and increase the expression of growth factors to improve angiogenesis.
Field-enhanced emission rate and electronic properties of a defect introduced in n-GaN by 5.4 MeV He-ion irradiation

A deep level defect ER3, introduced in n-GaN by high energy (5.4 MeV) He ions, was characterized by deep level transient spectroscopy (DLTS). This defect, 0.196±0.004 eV below the conduction band, with an apparent capture cross-section of 3.5±1×10−15 cm2, is introduced uniformly in the region profiled by DLTS at a rate of 3270±200 cm−1. The emission rate of this defect depends on the electric field strength in the space-charge region. This emission rate is modeled according to the Poole–Frenkel distortion of a square well with a radius of 20±2 A or alternatively, a Gaussian well with a characteristic width of 6.0±1 A. Hence, we conclude that ER3 is a point defect which has a field dependence not explained by the classical Poole–Frenkel enhancement.
Resting state network mapping in individuals using deep learning

Introduction Resting state functional MRI (RS-fMRI) is currently used in numerous clinical and research settings. The localization of resting state networks (RSNs) has been utilized in applications ranging from group analysis of neurodegenerative diseases to individual network mapping for pre-surgical planning of tumor resections. Reproducibility of these results has been shown to require a substantial amount of high-quality data, which is not often available in clinical or research settings. Methods In this work, we report voxelwise mapping of a standard set of RSNs using a novel deep 3D convolutional neural network (3DCNN). The 3DCNN was trained on publicly available functional MRI data acquired in n = 2010 healthy participants. After training, maps that represent the probability of a voxel belonging to a particular RSN were generated for each participant, and then used to calculate mean and standard deviation (STD) probability maps, which are made publicly available. Further, we compared our results to previously published resting state and task-based functional mappings. Results Our results indicate this method can be applied in individual subjects and is highly resistant to both noisy data and fewer RS-fMRI time points than are typically acquired. Further, our results show core regions within each network that exhibit high average probability and low STD. Discussion The 3DCNN algorithm can generate individual RSN localization maps, which are necessary for clinical applications. The similarity between 3DCNN mapping results and task-based fMRI responses supports the association of specific functional tasks with RSNs.
Graphs of protein-water hydrogen bond networks to dissect structural movies of ion-transfer microbial rhodopsins

Microbial rhodopsins are membrane proteins that use the energy absorbed by the covalently bound retinal chromophore to initiate reaction cycles resulting in ion transport or signal transduction. Thousands of distinct microbial rhodopsins are known and, for many rhodopsins, three-dimensional structures have been solved with structural biology, including as entire sets of structures solved with serial femtosecond crystallography. This sets the stage for comprehensive studies of large datasets of static protein structures to dissect structural elements that provide functional specificity to the various microbial rhodopsins. A challenge, however, is how to analyze efficiently intra-molecular interactions based on large datasets of static protein structures. Our perspective discusses the usefulness of graph-based approaches to dissect structural movies of microbial rhodopsins solved with time-resolved crystallography.
Efficacy and safety of transarterial chemoembolization plus sorafenib in patients with recurrent hepatocellular carcinoma after liver transplantation

Objectives To explore the benefit and safety of transarterial chemoembolization (TACE) in combination with sorafenib in patients with recurrent hepatocellular carcinoma (HCC) after orthotopic liver transplantation (OLT). Methods In this multi-center retrospective study, 106 patients with recurrent HCC after OLT were included. Fifty-two patients were treated with TACE plus sorafenib (TS group) and 54 were treated with TACE alone (TC group). Primary and secondary endpoints including overall survival (OS) and progression-free survival (PFS), and safety were assessed. Results The median OS (17 vs 10 months, P=0.035) and PFS (12 vs 6 months, P=0.004) in the TS group were longer than those in the TC group. On multivariate analysis, BCLC stage (HR [hazard ratio]=0.73 [95% CI, 0.27–0.99], P=0.036) and sorafenib medication (HR=2.26 [95% CI, 1.35–3.69], P=0.01) were identified as independent prognostic risk factors for OS. No severe adverse events related to sorafenib were noted in the TS group. Four patients discontinued sorafenib due to intolerance. Conclusion TACE in combination with sorafenib is a feasible regimen to improve the survival with mild toxicity in patients with recurrent HCC after OLT.
Three levels at which the user's cognition can be represented in artificial intelligence

Artificial intelligence (AI) plays an important role in modern society. AI applications are omnipresent and assist many decisions we make in daily life. A common and important feature of such AI applications are user models. These models allow an AI application to adapt to a specific user. Here, we argue that user models in AI can be optimized by modeling these user models more closely to models of human cognition. We identify three levels at which insights from human cognition can be—and have been—integrated in user models. Such integration can be very loose with user models only being inspired by general knowledge of human cognition or very tight with user models implementing specific cognitive processes. Using AI-based applications in the context of education as a case study, we demonstrate that user models that are more deeply rooted in models of cognition offer more valid and more fine-grained adaptations to an individual user. We propose that such user models can also advance the development of explainable AI.
Editorial: The medial septum as a smart clock: New aspects of its function beyond pacemaking

COPYRIGHT © 2023 Hangya and Varga. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Editorial: The medial septum as a smart clock: New aspects of its function beyond pacemaking
Comprehensive genome-scale metabolic model of the human pathogen Cryptococcus neoformans: A platform for understanding pathogen metabolism and identifying new drug targets

Introduction: The fungal priority pathogen Cryptococcus neoformans causes cryptococcal meningoencephalitis in immunocompromised individuals and leads to hundreds of thousands of deaths per year. The undesirable side effects of existing treatments, the need for long application times to prevent the disease from recurring, the lack of resources for these treatment methods to spread over all continents necessitate the search for new treatment methods. Methods: Genome-scale models have been shown to be valuable in studying the metabolism of many organisms. Here we present the first genome-scale metabolic model for C. neoformans, iCryptococcus. This comprehensive model consists of 1,270 reactions, 1,143 metabolites, 649 genes, and eight compartments. The model was validated, proving accurate when predicting the capability of utilizing different carbon and nitrogen sources and growth rate in comparison to experimental data. Results and Discussion: The compatibility of the in silico Cryptococcus metabolism under infection conditions was assessed. The steroid and amino acid metabolisms found in the essentiality analyses have the potential to be drug targets for the therapeutic strategies to be developed against Cryptococcus species. iCryptococcus model can be applied to explore new targets for antifungal drugs along with essential gene, metabolite and reaction analyses and provides a promising platform for elucidation of pathogen metabolism.
Molecular mechanism of LIP05 derived from Monascus purpureus YJX-8 for synthesizing fatty acid ethyl esters under aqueous phase

Fatty acid ethyl esters are important flavor chemicals in strong-flavor Baijiu. Monascus purpureus YJX-8 is recognized as an important microorganism for ester synthesis in the fermentation process. Enzyme LIP05 from YJX-8 can efficiently catalyze the synthesis of fatty acid ethyl esters under aqueous phase, but the key catalytic sites affecting esterification were unclear. The present work combined homology modeling, molecular dynamics simulation, molecular docking and site-directed mutation to analyze the catalytic mechanism of LIP05. Protein structure modeling indicated LIP05 belonged to α/β fold hydrolase, contained a lid domain and a core catalytic pocket with conserved catalytic triad Ser150-His215-Asp202, and the oxyanion hole composed of Gly73 and Thr74. Ile30 and Leu37 of the lid domain were found to affect substrate specificity. The π-bond stacking between Tyr116 and Tyr149 played an important role in stabilizing the catalytic active center of LIP05. Tyr116 and Ile204 determined the substrate spectrum by composing the substrate-entrance channel. Residues Leu83, Ile204, Ile211 and Leu216 were involved in forming the hydrophobic substrate-binding pocket through steric hindrance and hydrophobic interaction. The catalytic mechanism for esterification in aqueous phase of LIP05 was proposed and provided a reference for clarifying the synthesis of fatty acid ethyl esters during the fermentation process of strong-flavor Baijiu.
Does integument arise de novo or from pre-existing structures? ── Insights from the key regulatory genes controlling integument development

The origin of seeds is one of the key innovations in land plant evolution. Ovules are the developmental precursors of seeds. The integument is the envelope structure surrounding the nucellus within the ovule and developing into the seed coat when ovules mature upon fertilization. The question of whether the integument arise de novo or evolve from elaboration of pre-existing structures has caused much debate. By exploring the origin and evolution of the key regulatory genes controlling integument development and their functions during both individual and historical developmental processes, we showed the widespread presence of the homologs of ANT, CUC, BEL1, SPL, C3HDZ, INO, ATS, and ETT in seedless plant genomes. All of these genes have undergone duplication-divergence events in their evolutionary history, with most of the descendant paralogous suffering motif gain and/or loss in the coding regions. Expression and functional characterization have shown that these genes are key components of the genetic program that patterns leaf-like lateral organs. Serial homology can thus be postulated between integuments and other lateral organs in terms of the shared master regulatory genes. Given that the genetic program patterning leaf-like lateral organs formed in seedless plants, and was reused during seed origin, the integument is unlikely to arise de novo but evolved from the stem segment-specific modification of pre-existing serially homologous structures. The master ‘switches’ trigging the modification to specify the integument identity remain unclear. We propose a successive transformation model of integument origin.
A detection model of scaling attacks considering consumption pattern diversity in AMI

As an important branch of the Internet of Things, the smart grid has become a crucial field of modern information technology. It realizes the two-way information flow and power flow by integrating the advanced metering infrastructure (AMI) and distributed energy resources, which greatly improves users’ participation. However, owing to smart meters, the most critical components of AMI, are deployed in an open network environment, AMI is a potential target for data integrity attacks. Among various attack types, the scaling attack is the most typical one, because it can be used as a general expression for most of other ones. By launching a scaling attack, adversaries can randomly reduce hourly reported values in smart meters, thereby causing economic losses. A number of research efforts have been devoted to detecting data integrity attacks. Nonetheless, most of the existing investigations focus on all attack types, and little attention has been paid to a detection strategy specially designed for scaling attacks. Our contribution addresses this issue in this paper and hence, developing a detection model of scaling attacks considering consumption pattern diversity (SA2CPD), to ensure that scaling attacks can be effectively detected when users have multiple consumption patterns. To be specific, we leverage Kmeans to distinguish different consumption patterns, and then the consumption intervals can be extracted to binarize the data. We divide time periods in every day into two categories based on the binarization values, and use one of them with the greatest information gain to construct a decision tree for judgment. Both theoretical and simulation results based on the GEFCom2012 dataset show that our SA2CPD model has a higher F1 score than the decision tree model without considering consumption pattern diversity, the KNN model and the Naive Bayes model.
Effect of increased protein intake and exogenous ketosis on body composition, energy expenditure and exercise capacity during a hypocaloric diet in recreational female athletes

Introduction: Since low body weight is an important determinant of success in many sports such as gymnastics, martial arts and figure skating, athletes can benefit from effective weight loss strategies that preserve muscle mass and athletic performance. The present study investigates the effects of increased protein intake and exogenous ketosis on body composition, energy expenditure, exercise capacity, and perceptions of appetite and well-being during a hypocaloric diet in females. Methods: Thirty-two female recreational athletes (age: 22.2 ± .5 years; body weight: 58.3 ± .8 kg; BMI: 20.8 ± .2 kg·m−2) underwent 4 weeks of 30% caloric restriction and were randomized to receive either an increased daily amount of dietary protein (PROT, ∼2.0–2.2 g protein·kg−1·day−1), 3 × 20 g·day−1 of a ketone ester (KE), or an isocaloric placebo (PLA). Body composition was measured by DXA, resting energy expenditure (REE) by indirect calorimetry, exercise capacity during a VO2max test, appetite hormones were measured in serum, and perceptions of general well-being were evaluated via questionnaires. Results: The hypocaloric diet reduced body weight by 3.8 ± . 3 kg in PLA, 3.2 ± . 3 kg in KE and 2.4 ± . 2 kg in PROT (Ptime<.0001). The drop in fat mass was similar between treatments (average: 2.6 ± .1 kg, Ptime<.0001), while muscle mass was only reduced in PLA and KE (average: .8 ± .2 kg, Ptime<.05), and remained preserved in PROT (Pinteraction<.01). REE [adjusted for lean mass] was reduced after caloric restriction in PLA (pre: 32.7 ± .5, post: 28.5 ± .6 kcal·day−1·kg−1) and PROT (pre: 32.9 ± 1.0, post: 28.4 ± 1.0 kcal·day−1·kg−1), but not in KE (pre: 31.8 ± .9, post: 30.4 ± .8 kcal·day−1·kg−1) (Pinteraction<.005). Furthermore, time to exhaustion during the VO2max test decreased in PLA (by 2.5 ± .7%, p < .05) but not in KE and PROT (Pinteraction<.05). Lastly, the perception of overall stress increased in PLA and PROT (p < .05), but not in KE (Pinteraction<.05). Conclusion: Increased protein intake effectively prevented muscle wasting and maintained exercise capacity during a period of caloric restriction in female recreational athletes. Furthermore, exogenous ketosis did not affect body composition, but showed its potential in weight management by preserving a drop in exercise capacity and REE and by improving overall stress parameters during a period of caloric restriction.
An assessment of enhanced biosecurity interventions and their impact on porcine reproductive and respiratory syndrome virus outbreaks within a managed group of farrow-to-wean farms, 2020–2021

Introduction Porcine reproductive and respiratory syndrome virus (PRRSV) has been a challenge for the U.S. swine industry for over 30 years, costing producers more than $600 million annually through reproductive disease in sows and respiratory disease in growing pigs. In this study, the impact of enhanced biosecurity practices of site location, air filtration, and feed mitigation was assessed on farrow-to-wean sites managed by a large swine production management company in the Midwest United States. Those three factors varied in the system that otherwise had implemented a stringent biosecurity protocol on farrow-to-wean sites. The routine biosecurity followed commonplace activities for farrow-to-wean sites that included but were not limited to visitor registration, transport disinfection, shower-in/shower-out procedures, and decontamination and disinfection of delivered items and were audited. Methods Logistic regression was used to evaluate PRRSV infection by site based on the state where the site is located and air filtration use while controlling for other variables such as vaccine status, herd size, and pen vs. stall. A descriptive analysis was used to evaluate the impact of feed mitigation stratified by air filtration use. Results Sites that used feed mitigates as additives in the diets, air filtration of barns, and that were in less swine-dense areas appeared to experience fewer outbreaks associated with PRRSV infection. Specifically, 23.1% of farms that utilized a feed mitigation program experienced PRRSV outbreaks, in contrast to 100% of those that did not. Sites that did not use air filtration had 20 times greater odds of having a PRRSV outbreak. The strongest protective effect was found when both air filtration and feed mitigation were used. Locations outside of Minnesota and Iowa had 98.5–99% lesser odds of infection as well. Discussion Enhanced biosecurity practices may yield significant protective effects and should be considered for producers in swine-dense areas or when the site contains valuable genetics or many pigs.
Audiological and psychological assessment of tinnitus patients with normal hearing

Introduction This study was performed to assess identifiable abnormalities in tinnitus patients with normal hearing. Methods The medical records of subjective non-pulsatile tinnitus patients with normal hearing confirmed by conventional pure-tone audiometry who visited our tinnitus clinic between March 2020 and May 2022 were reviewed. The loudness discomfort level (LDL), extended high-frequency hearing loss (EHFHL), summating potential (SP)/action potential (AP) ratio, distortion product otoacoustic emission (DPOAE), thresholds of auditory brainstem response (ABR) wave V, somatic modulation, and psychiatric symptoms, such as anxiety, depression, and stress were evaluated by questionnaires. Results Decreased LDL (n = 48, 59.8%) was the most frequent finding, followed by EHFHL (n = 29, 35.4%), increased SP/AP ratio (n = 27, 32.9%), psychiatric symptoms (n = 24, 29.3%), decreased DPOAE (n = 17, 20.7%), somatic modulation (n = 8, 9.8%), and increased ABR threshold (n = 3, 3.7%); 75.6% of patients had one or more of these findings. The presence of psychiatric symptoms was independently associated with the Tinnitus Handicap Inventory (THI) score. Conclusion Tinnitus in patients with normal hearing may be accompanied by a combination of various subclinical abnormal audiological findings. However, the presence of psychiatric symptoms alone was independently associated with tinnitus distress.
Transcriptomic comparison of seeds and silique walls from two rapeseed genotypes with contrasting seed oil content

Silique walls play pivotal roles in contributing photoassimilates and nutrients to fuel seed growth. However, the interaction between seeds and silique walls impacting oil biosynthesis is not clear during silique development. Changes in sugar, fatty acid and gene expression during Brassica napus silique development of L192 with high oil content and A260 with low oil content were investigated to identify key factors affecting difference of their seed oil content. During the silique development, silique walls contained more hexose and less sucrose than seeds, and glucose and fructose contents in seeds and silique walls of L192 were higher than that of A260 at 15 DAF, and sucrose content in the silique walls of L192 were lower than that of A260 at three time points. Genes related to fatty acid biosynthesis were activated over time, and differences on fatty acid content between the two genotypes occurred after 25 DAF. Genes related to photosynthesis expressed more highly in silique walls than in contemporaneous seeds, and were inhibited over time. Gene set enrichment analysis suggested photosynthesis were activated in L192 at 25 and 35 DAF in silique walls and at both 15 and 35 DAF in the seed. Expressions of sugar transporter genes in L192 was higher than that in A260, especially at 35 DAF. Expressions of genes related to fatty acid biosynthesis, such as BCCP2s, bZIP67 and LEC1s were higher in L192 than in A260, especially at 35 DAF. Meanwhile, genes related to oil body proteins were expressed at much lower levels in L192 than in A260. According to the WGCNA results, hub modules, such as ME.turquoise relative to photosynthesis, ME.green relative to embryo development and ME.yellow relative to lipid biosynthesis, were identified and synergistically regulated seed development and oil accumulation. Our results are helpful for understanding the mechanism of oil accumulation of seeds in oilseed rape for seed oil content improvement.