Miracle-dz/UniFAR-FTUs huggingface dataset:
The untapped potential of macrofossils in ancient plant DNA research

Summary The rapid development of ancient DNA analysis in the last decades has induced a paradigm shift in ecology and evolution. Driven by a combination of breakthroughs in DNA isolation techniques, high‐throughput sequencing, and bioinformatics, ancient genome‐scale data for a rapidly growing variety of taxa are now available, allowing researchers to directly observe demographic and evolutionary processes over time. However, the vast majority of paleogenomic studies still focus on human or animal remains. In this article, we make the case for a vast untapped resource of ancient plant material that is ideally suited for paleogenomic analyses: plant remains, such as needles, leaves, wood, seeds, or fruits, that are deposited in natural archives, such as lake sediments, permafrost, or even ice caves. Such plant remains are commonly found in large numbers and in stratigraphic sequence through time and have so far been used primarily to reconstruct past local species presences and abundances. However, they are also unique repositories of genetic information with the potential to revolutionize the fields of ecology and evolution by directly studying microevolutionary processes over time. Here, we give an overview of the current state‐of‐the‐art, address important challenges, and highlight new research avenues to inspire future research.
Improvement of sleep by resistant dextrin prebiotic in type 2 diabetic women coincides with attenuation of metabolic endotoxemia: Involvement of gut-brain axis.

BACKGROUND Resistant dextrin, as a prebiotic and functional food, may possess favorable effects in type 2 diabetes. This study was conducted to assess whether supplementation with resistant dextrin can improve sleep and quality of life in obese type 2 diabetic women. RESULTS In this randomized controlled trial, female obese type 2 diabetic patients (n=76) were randomly assigned into intervention group (n=38) and placebo group (n=38), and received 10g/d of resistant dextrin or maltodextrin for a period of 8 weeks, respectively. Sleep quality and quality of life (QOL) were assessed by Pittsburgh Sleep Quality Index (PSQI) and SF-36 health survey, respectively. Fasting blood samples were driven to measure serum bacterial endotoxin, fasting blood sugar, glycosylated hemoglobin (HbA1c), pro-inflammatory/anti-inflammatory biomarkers (IL-18, IL-6, IL-10, TNF-α), and biomarkers of hypothalamicpituitary-adrenal axis function [tryptophan (TRP), adrenocorticotropic hormone (ACTH), kynurenine (KYN), cortisol]. Supplementation with resistant dextrin improved sleep (p<0.001) and QOL (p<0.001) significantly. It also caused a significant decrease in levels of endotoxin, HbA1c, IL-18, IL-6, TNF-α and a significant increase in IL-10 levels. Significant and positive correlations were found between endotoxin (r=0.488, p=0.003), IL-6 (r=0.436, p=0.008), IL-18 (r=0.475, p=0.003), cortisol (r=0.545, p=0.048), KYN/TRP (r=0.527, p=0.001), and PSQI scores. CONCLUSIONS It is concluded that resistant dextrin improves sleep and quality of life in obese women with type 2 diabetes. Its beneficial effects may be attributed in part to modulation of glycemia, metabolic endotoxemia and subsequently a decrease in biomarkers of inflammation, and hypothalamic-pituitary- adrenal axis activity. This article is protected by copyright. All rights reserved.
Theoretical Study on a Large Radius Coaxial Cavity Terahertz Gyrotron

In order to develop high power Terahertz sources,a large radius coaxial cavity gyrotron has been studied in this paper.The results of theoretical calculation show that in a coaxial cavity the cutoff frequency of TE0n mode is almost proportional to n and in inverse proportion to the distance between inner and outer conductor.According to these characteristics a large radius coaxial cavity 0.3THz TE04 mode gyrotron is designed.The results of numerical calculation and PIC simulation show the large radius coaxial gyrotrons have a lot of advantages compared with the waveguide gyrotrons:the size of coaxial cavity is comparatively larger and outpwt power can be increased.The interval between TE0n and TEmn mode is increased which has improved mode competition greatly.
The multifaceted role of cytochrome P450-Derived arachidonic acid metabolites in diabetes and diabetic cardiomyopathy

Abstract Understanding lipid metabolism is a critical key to understanding the pathogenesis of Diabetes Mellitus (DM). It is known that 60–90% of DM patients are obese or used to be obese. The incidence of obesity is rising owing to the modern sedentary lifestyle that leads to insulin resistance and increased levels of free fatty acids, predisposing tissues to utilize more lipids with less glucose uptake. However, the exact mechanism is not yet fully elucidated. Diabetic cardiomyopathy seems to be associated with these alterations in lipid metabolism. Arachidonic acid (AA) is an important fatty acid that is metabolized to several bioactive compounds by cyclooxygenases, lipoxygenases, and the more recently discovered, cytochrome P450 (P450) enzymes. P450 metabolizes AA to either epoxy-AA (EETs) or hydroxy-AA (HETEs). Studies showed that EETs could have cardioprotective effects and beneficial effects in reversing abnormalities in glucose and insulin homeostasis. Conversely, HETEs, most importantly 12-HETE and 20-HETE, were found to interfere with normal glucose and insulin homeostasis and thus, might be involved in diabetic cardiomyopathy. In this review, we highlight the role of P450-derived AA metabolites in the context of DM and diabetic cardiomyopathy and their potential use as a target for developing new treatments for DM and diabetic cardiomyopathy.
The Addition of United States Census-Tract Data Does Not Improve the Prediction of Substance Misuse

Predictors from the structured data in the electronic health record (EHR) have previously been used for case-identification in substance misuse. We aim to examine the added benefit from census-tract data, a proxy for socioeconomic status, to improve identification. A cohort of 186,611 hospitalizations was derived between 2007 and 2017. Reference labels included alcohol misuse only, opioid misuse only, and both alcohol and opioid misuse. Baseline models were created using 24 EHR variables, and enhanced models were created with the addition of 48 census-tract variables from the United States American Community Survey. The absolute net reclassification index (NRI) was applied to measure the benefit in adding census-tract variables to baseline models. The baseline models already had good calibration and discrimination. Adding census-tract variables provided negligible improvement to sensitivity and specificity and NRI was less than 1% across substance groups. Our results show the census-tract added minimal value to prediction models.
Environmental overlap influences goal‐oriented coding of spatial sequences differently along the long‐axis of hippocampus

When navigating our world we often first plan or retrieve a route to our goal, avoiding alternative paths to other destinations. Inspired by computational and animal models, we have recently demonstrated evidence that the human hippocampus supports prospective spatial coding, mediated by interactions with the prefrontal cortex. But the relationship between such signals and the need to discriminate possible routes based on their goal remains unclear. In the current study, we combined human fMRI, multi‐voxel pattern analysis, and an established paradigm for contrasting memories of nonoverlapping routes with those of routes that cross paths and must be disambiguated. By classifying goal‐oriented representations at the initiation of a navigational route, we demonstrate that environmental overlap modulates goal‐oriented representations in the hippocampus. This modulation manifest through representational shifts from posterior to anterior components of the right hippocampus. Moreover, declines in goal‐oriented decoding due to overlapping memories were predicted by the strength of the alternative memory, suggesting co‐expression and competition between alternatives in the hippocampus during prospective thought. Moreover, exploratory whole‐brain analyses revealed that a region of frontopolar cortex, which we have previously tied to prospective route planning, represented goal‐states in new overlapping routes. Together, our findings provide insight into the influences of contextual overlap on the long‐axis of the hippocampus and a broader memory and planning network that we have long‐associated with such navigation tasks.
DIABETES MELLITUS TYPE 1 IN ADOLESCENTS: IMPACT OF VITAMIN D STATUS.

OBJECTIVE The aim: To evaluate the effect of vitamin D deficiency or insufficiency on the compensation of the disease in adolescents with diabetes mellitus type 1. PATIENTS AND METHODS Materials and methods: 124 patients were examined, among them: 33 from the control group, 91 adolescents with type 1 diabetes mellitus. All patients were between 10-18 years old and were residents of the Podillya region of Ukraine. RESULTS Results: According to the results of the study Vitamin D levels in adolescents with type 1 diabetes mellitus are significantly lower, comparing with healthy adolescents of the same age group. Vitamin D levels among boys with type 1 diabetes mellitus were significantly lower comparing to girls of the same group. The boys of the control group had significantly higher levels of vitamin D in the blood comparing to boys with type 1 diabetes mellitus, p <0.001. CONCLUSION Conclusions: The majority of adolescents aged 13-18 years with type 1 diabetes mellitus have vitamin D deficiency or insufficiency regardless of the state of glycemic control of the disease.
Carbon starvation, senescence and specific mitochondrial stresses, but not nitrogen starvation and general stresses, are major triggers for mitophagy in Arabidopsis

ABSTRACT Selective degradation of mitochondria by autophagy (mitophagy) is thought to play an important role in mitochondrial quality control, but our understanding of which conditions induce mitophagy in plants is limited. Here, we developed novel reporter lines to monitor mitophagy in plants and surveyed the rate of mitophagy under a wide range of stresses and developmental conditions. Especially carbon starvation induced by dark-incubation causes a dramatic increase in mitophagy within a few hours, further increasing as dark-induced senescence progresses. Natural senescence was also a strong trigger of mitophagy, peaking when leaf yellowing became prominent. In contrast, nitrogen starvation, a trigger of general autophagy, does not induce strong increases in mitophagy. Similarly, general stresses such as hydrogen peroxide, heat, UV-B and hypoxia did not appear to trigger substantial mitophagy in plants. Additionally, we exposed plants to inhibitors of the mitochondrial electron transport chain, mitochondrial translation and protein import. Although short-term treatments did not induce high mitophagy rates, longer term exposures to uncoupling agent and inhibitors of mitochondrial protein import/translation could clearly increase mitophagic flux. These findings could further be confirmed using confocal microscopy. To validate that mitophagy is mediated by the autophagy pathway, we showed that mitophagic flux is abolished or strongly decreased in atg5/AuTophaGy 5 and atg11 mutants, respectively. Finally, we observed high rates of mitophagy in etiolated seedlings, which remarkably was completely repressed within 6 h after light exposure. In conclusion, we propose that dark-induced carbon starvation, natural senescence and specific mitochondrial stresses are key triggers of mitophagy in plants. Abbreviations: AA: antimycin A; ATG: AuToPhagy related; ConA: concanamycin A; DIS: dark-induced senescence; Dox: doxycycline; FCCP: carbonyl cyanide-p-trifluoromethoxyphenylhydrazone; GFP: green fluorescent protein; IDH1: isocitrate dehydrogenase 1; MB: MitoBlock-6; Mito-GFP: transgenic Arabidopsis line expressing a mitochondrially targeted protein fused to GFP; mtETC: mitochondrial electron transport chain; OXPHOS: oxidative phosphorylation; PQC: protein quality control; TOM20: Translocase of Outer Membrane 20
Gelsemium elegans cyclic peptide induces human cervical carcinoma cells apoptosis through intrinsic and extrinsic pathways

Four novel Gelsemium elegans cyclic peptides (GEPs) were isolated in an antihuman cervical carcinoma activity tracking method, and their amino acid sequences were identified. The GEP‐1 cyclic‐(Trp‐Leu‐His‐Val)‐peptide inhibited HeLa cell proliferation in a dose‐ and time‐dependent manner. GEP‐1 induced intracellular reactive oxygen species (ROS) overproduction and induced HeLa cells apoptosis in a caspase‐dependent manner. GEP‐1 also induced collapse of the mitochondrial membrane potential and promoted the mitochondrial release of cytochrome c (cyt c), apoptosis‐inducing factor (AIF), and endonuclease G (Endo G) in HeLa cells. Furthermore, GEP‐1 triggered the extrinsic death receptor‐dependent pathway, which was characterized by activating Fas and FADD. Notably, GEP‐1 is a potential antihuman cervical carcinoma peptide.
Controversial Trials First: Identifying Disagreement Between Clinical Guidelines and New Evidence

Clinical guidelines integrate latest evidence to support clinical decision-making. As new research findings are published at an increasing rate, it would be helpful to detect when such results disagree with current guideline recommendations. In this work, we describe a software system for the automatic identification of disagreement between clinical guidelines and published research. A critical feature of the system is the extraction and cross-lingual normalization of information through natural language processing. The initial version focuses on the detection of cancer treatments in clinical trial reports that are not addressed in oncology guidelines. We evaluate the relevance of trials retrieved by our system retrospectively by comparison with historic guideline updates and also prospectively through manual evaluation by guideline experts. The system improves precision over state-of-the-art literature research strategies while maintaining near-total recall. Detailed error analysis highlights challenges for fine-grained clinical information extraction, in particular when extracting population definitions for tumor-agnostic therapies.
Sea level rise and climate change acting as interactive stressors on development and dynamics of tropical peatlands in coastal Sumatra and South Borneo since the Last Glacial Maximum

Southeast Asian peatlands, along with their various important ecosystem services, are mainly distributed in the coastal areas of Sumatra and Borneo. These ecosystems are threatened by coastal development, global warming and sea level rise (SLR). Despite receiving growing attention for their biodiversity and as massive carbon stores, there is still a lack of knowledge on how they initiated and evolved over time, and how they responded to past environmental change, that is, precipitation, sea level and early anthropogenic activities. To improve our understanding thereof, we conducted multi‐proxy paleoecological studies in the Kampar Peninsula and Katingan peatlands in the coastal area of Riau and Central Kalimantan, Indonesia. The results indicate that the initiation timing and environment of both peatlands are very distinct, suggesting that peat could form under various vegetation as soon as there is sufficient moisture to limit organic matter decomposition. The past dynamics of both peatlands were mainly attributable to natural drivers, while anthropogenic activities were hardly relevant. Changes in precipitation and sea level led to shifts in peat swamp forest vegetation, peat accumulation rates and fire regimes at both sites. We infer that the simultaneous occurrence of El Niño‐Southern Oscillation (ENSO) events and SLR resulted in synergistic effects which led to the occurrence of severe fires in a pristine coastal peatland ecosystem; however, it did not interrupt peat accretion. In the future, SLR, combined with the projected increase in frequency and intensity of ENSO, can potentially amplify the negative effects of anthropogenic peatland fires. This prospectively stimulates massive carbon release, thus could, in turn, contribute to worsening the global climate crisis especially once an as yet unknown threshold is crossed and peat accretion is halted, that is, peatlands lose their carbon sink function. Given the current rapid SLR, coastal peatland managements should start develop fire risk reduction or mitigation strategies.
Chemodiversity, Biological Activities and Molecular Docking Studies of Leptadenia pyrotechnica (Forssk.) Decne: A Comprehensive Approach to Validate Its Medicinal Use.

Leptadenia pyrotechnica (Forssk.) Decne is growing in Cholistan desert, and is known for its laxative, analgesic, anabolic and astringent, antioxidant, anti‐inflammatory, antibacterial, antitumor, hypolipidemic and antiatherosclerotic properties. The present study disclosed the metabolic picture of L. pyrotechnica and validates its folk uses. LP‐H fraction constitute 25.79±0.11 mgGAE/g extract and 20.64±0.33 mgRE/g extract of phenolic and flavonoid content, respectively, followed by LP‐E (23.15±0.33 mgGAE/g extract and 19.40±0.13 mgRE/g extract), however, LP‐E exhibited the highest free radical scavenging (DPPH: 21.05±0.45mgTE/g and ABTS: 68.12±0.53 mgTE/g) and metal reducing (FRAP: 44.93±1.66, CUPRAC: 117.42±1.28 mgTE/g, respectively) activities. The total antioxidant capacity in Phosphomolybdenum assay (1.52±0.14 mmolTE/g) and ferrous ion chelating (11.57±0.29 mgEDTAE/g) activities were observed highest for LP‐H extract. In cholinesterase's inhibitory assays, the LP‐E and LP‐W extracts exhibited inhibitory values as 2.43 and 2.40±0.07 mgGALAE/g extract, respectively against AChE, while against BChE the LP‐H displayed the highest value as 5.98±0.44 mgGALAE/g extract. The LP‐H fraction also showed the highest inhibition potential (7.72±0.14 mmol ACAE/g and 0.55±0.01 mmol ACAE/g, respectively) against α‐glucosidase and α‐amylase enzymes, while, in tyrosinase inhibitory assay, all the fractions exhibited significant activities in the range of 59.35±0.29 to 55.18±0.49 mgKAE/g extract. RP‐UHPLC/MS analysis of LP‐M disclosed the presence of 57 metabolites of various classes. A multivariate analysis and molecular docking study was also carried out to establish relationships between the metabolites and the biological activities, which finally validate the use of L. pyrotechnica as herbal medicine or component nutraceutical, food and cosmetic industry.
The Prognostic Utility of Electroencephalography in Stroke Recovery: A Systematic Review and Meta-Analysis

Background Improved ability to predict patient recovery would guide post-stroke care by helping clinicians personalize treatment and maximize outcomes. Electroencephalography (EEG) provides a direct measure of the functional neuroelectric activity in the brain that forms the basis for neuroplasticity and recovery, and thus may increase prognostic ability. Objective To examine evidence for the prognostic utility of EEG in stroke recovery via systematic review/meta-analysis. Methods Peer-reviewed journal articles that examined the relationship between EEG and subsequent clinical outcome(s) in stroke were searched using electronic databases. Two independent researchers extracted data for synthesis. Linear meta-regressions were performed across subsets of papers with common outcome measures to quantify the association between EEG and outcome. Results 75 papers were included. Association between EEG and clinical outcomes was seen not only early post-stroke, but more than 6 months post-stroke. The most studied prognostic potential of EEG was in predicting independence and stroke severity in the standard acute stroke care setting. The meta-analysis showed that EEG was associated with subsequent clinical outcomes measured by the Modified Rankin Scale, National Institutes of Health Stroke Scale, and Fugl-Meyer Upper Extremity Assessment (r = .72, .70, and .53 from 8, 13, and 12 papers, respectively). EEG improved prognostic abilities beyond prediction afforded by standard clinical assessments. However, the EEG variables examined were highly variable across studies and did not converge. Conclusions EEG shows potential to predict post-stroke recovery outcomes. However, evidence is largely explorative, primarily due to the lack of a definitive set of EEG measures to be used for prognosis.
Overexpression of Tetraspanin31 contributes to malignant potential and poor outcomes in gastric cancer

Tetraspanin has important functions in many cancers by aggregating with various proteins that interact with intracellular signaling proteins. The molecular function of Tetraspanin31 (TSPAN31), located in the 12q14 amplified region in various cancers, remains unclear in gastric cancer (GC). We tested whether TSPAN31 acts as a cancer‐promoting gene through its activation or overexpression in GC. We analyzed seven GC cell lines and 189 primary tumors, which were curatively resected in our hospital between 2011 and 2013. Overexpression of the TSPAN31 protein was frequently detected in three GC cell lines (42.9%) and 62 primary GC specimens (32.8%). Overexpression of TSPAN31 was significantly correlated with lymphatic invasion, venous invasion, more advanced pT and pN stages, and a higher recurrence rate. Moreover, TSPAN31 positivity was an independent factor predicting worse patient outcomes (p = 0.0283, hazard ratio 3.97). Ectopic overexpression of TSPAN31 facilitated cell proliferation of GC cells, and knockdown of TSPAN31 inhibited cell proliferation, migration, invasion, and epithelial–mesenchymal transition of GC cells through the PI3K‐Akt pathway and increased cell apoptosis in a TP53 mutation‐independent manner. In vivo analysis also revealed knockdown of TSPAN31 suppressed tumor progression. In addition, knockdown of TSPAN31 improved chemosensitivity to cisplatin through the suppression of ABCC2. These findings suggest that TSPAN31 plays a crucial role in tumor‐malignant potential through overexpression, highlighting its utility as a prognostic factor and a potential therapeutic target in GC.
P2RY14 cAMP signaling regulates Schwann cell precursor self-renewal, proliferation, and nerve tumor initiation in a mouse model of neurofibromatosis

Neurofibromatosis type 1 (NF1) is characterized by nerve tumors called neurofibromas, in which Schwann cells (SCs) show deregulated RAS signaling. NF1 is also implicated in regulation of cAMP. We identified the G-protein-coupled receptor (GPCR) P2ry14 in human neurofibromas, neurofibroma-derived SC precursors (SCPs), mature SCs, and mouse SCPs. Mouse Nf1-/- SCP self-renewal was reduced by genetic or pharmacological inhibition of P2ry14. In a mouse model of NF1, genetic deletion of P2ry14 rescued low cAMP signaling, increased mouse survival, delayed neurofibroma initiation, and improved SC Remak bundles. P2ry14 signals via Gi to increase intracellular cAMP, implicating P2ry14 as a key upstream regulator of cAMP. We found that elevation of cAMP by either blocking the degradation of cAMP or by using a P2ry14 inhibitor diminished NF1-/- SCP self-renewal in vitro and neurofibroma SC proliferation in in vivo. These studies identify P2ry14 as a critical regulator of SCP self-renewal, SC proliferation, and neurofibroma initiation.