Miracle-dz/UniFAR-FTUs huggingface dataset:
Seed dispersal and hoarding of three species by rodents in the Mt. Taihangshan Area, Jiyuan,China

Seed hoarders, such as small rodents, may adopt different eating and hoarding strategies for seeds of different plant species, and resulting in different plant seed dispersal patterns. At here, we tracked the seeds of three sympatric tree species: Quercus variabilis, Prunus armeniaca, Prunus persica, dispersed by small rodents in the Yugong State-owned Forestry Station, Jiyuan, Henan Province, Mt.Taihangshan area from September 10th to November 8th in 2011.We aimed to determine differences in harvest rates, seed fates, dispersal distances, cache sites and cache size among these seeds and understand the influence of rodents on seed dispersal of these sympatric tree species.The results showed that:1) Apodemus peninsulae and Sciurotamias davidianus were mainly responsible for the consumption and hoarding of the tested seeds; 2) Seed harvest rates varied significantly among different seed species, Q.variabilis (median survival times (MST): 8.6 d)P.armeniaca (MST: 20.9 d) P.persica (MST: 37.5 d); 3) A total of 55.0 % of Q.variabilis acorns were consumed, 62.0 % of P.armeniaca seeds were scatter-hoarded (buried in soil), whereas almost all of P.persica seeds (99.0 %) remained in situ; 4) Majorities seeds of P.armeniaca (88.6%) and Q.variabilis (78.9%) were hoarded either under shrubs, near the tree stems or near rock edges, whereas a few seeds of P.armeniaca (4.3%) and Q.variabilis (9.1%) were hoarded in the microhabitat of bare ground; 5) P.armeniaca seeds were dispersed farther from the seed sources (3.4±2.1 m, mean±SE, n=63) than were Q.variabilis acorns (2.5±2.4 m,n=57). These results suggest that small rodents are likely to adopt different hoarding strategies for sympatric plant seeds, and subsequently result in different plant seed dispersal patterns.
Application of the MSAP Technique to Evaluate Epigenetic Changes in Plant Conservation

Epigenetic variation, and particularly DNA methylation, is involved in plasticity and responses to changes in the environment. Conservation biology studies have focused on the measurement of this variation to establish demographic parameters, diversity levels and population structure to design the appropriate conservation strategies. However, in ex situ conservation approaches, the main objective is to guarantee the characteristics of the conserved material (phenotype and epi-genetic). We review the use of the Methylation Sensitive Amplified Polymorphism (MSAP) technique to detect changes in the DNA methylation patterns of plant material conserved by the main ex situ plant conservation methods: seed banks, in vitro slow growth and cryopreservation. Comparison of DNA methylation patterns before and after conservation is a useful tool to check the fidelity of the regenerated plants, and, at the same time, may be related with other genetic variations that might appear during the conservation process (i.e., somaclonal variation). Analyses of MSAP profiles can be useful in the management of ex situ plant conservation but differs in the approach used in the in situ conservation. Likewise, an easy-to-use methodology is necessary for a rapid interpretation of data, in order to be readily implemented by conservation managers.
The Dual Role of Glutamatergic Neurotransmission in Alzheimer’s Disease: From Pathophysiology to Pharmacotherapy

Alzheimer’s disease (AD) is an age-related dementia and neurodegenerative disorder, characterized by Aβ and tau protein deposition impairing learning, memory and suppressing synaptic plasticity of neurons. Increasing evidence suggests that there is a link between the glucose and glutamate alterations with age that down-regulates glucose utilization reducing glutamate levels in AD patients. Deviations in brain energy metabolism reinforce the development of AD by hampering glutamate levels in the brain. Glutamate is a nonessential amino acid and the major excitatory neurotransmitter synthesized from glucose. Alterations in cerebral glucose and glutamate levels precede the deposition of Aβ plaques. In the brain, over 40% of neuronal synapses are glutamatergic and disturbances in glutamatergic function have been implicated in pathophysiology of AD. Nevertheless, targeting the glutamatergic system seems to be a promising strategy to develop novel, improved therapeutics for AD. Here, we review data supporting the involvement of the glutamatergic system in AD pathophysiology as well as the efficacy of glutamatergic agents in this neurodegenerative disorder. We also discuss exciting new prospects for the development of improved therapeutics for this devastating disorder.
Defining the role of 17β‐estradiol in human endometrial stem cells differentiation into neuron‐like cells

Human endometrial stem cells (hEnSCs) that can be differentiated into various neural cell types have been regarded as a suitable cell population for neural tissue engineering and regenerative medicine. Considering different interactions between hormones, growth factors, and other factors in the neural system, several differentiation protocols have been proposed to direct hEnSCs towards specific neural cells. The 17β‐estradiol plays important roles in the processes of development, maturation, and function of nervous system. In the present research, the impact of 17β‐estradiol (estrogen, E2) on the neural differentiation of hEnSCs was examined for the first time, based on the expression levels of neural genes and proteins. In this regard, hEnSCs were differentiated into neuron‐like cells after exposure to retinoic acid (RA), epidermal growth factor (EGF), and also fibroblast growth factor‐2 (FGF2) in the absence or presence of 17β‐estradiol. The majority of cells showed a multipolar morphology. In all groups, the expression levels of nestin, Tuj‐1 and NF‐H (neurofilament heavy polypeptide) (as neural‐specific markers) increased during 14 days. According to the outcomes of immunofluorescence (IF) and real‐time PCR analyses, the neuron‐specific markers were more expressed in the estrogen‐treated groups, in comparison with the estrogen‐free ones. These findings suggest that 17β‐estradiol along with other growth factors can stimulate and upregulate the expression of neural markers during the neuronal differentiation of hEnSCs. Moreover, our findings confirm that hEnSCs can be an appropriate cell source for cell therapy of neurodegenerative diseases and neural tissue engineering.
Endoplasmic Reticulum Stress Affects Cholesterol Homeostasis by Inhibiting LXRα Expression in Hepatocytes and Macrophages

Atherosclerosis (AS) is the most common cardiovascular disease, and reverse cholesterol transport (RCT) plays an important role in maintaining cholesterol homeostasis. Both endoplasmic reticulum (ER) stress and LXRα can affect the metabolism of cholesterol. However, whether ER stress can modulate cholesterol metabolism by LXRα in hepatocytes and macrophages remains unclear. Therefore, in this study, we aimed to explore the relationship between ER stress induced by tunicamycin and LXRα in hepatocytes and macrophages and clarify their possible mechanisms and roles in AS. C57BL/6 mice and Huh-7 and THP-1 cells were treated with tunicamycin and LXR-623 (an agonist of LXRα) alone or in combination. Tunicamycin-induced ER stress caused liver injury; promoted the accumulation of cholesterol and triglycerides; inhibited the expression of LXRα, ABCA1 and ABCG1 in the livers of mice, thus reducing serum high-density lipoprotein (HDL)-C, low-density lipoprotein (LDL)-C, total cholesterol and triglyceride levels; however, LXR-623 could attenuate ER stress and reverse these changes. We also obtained the same results in Huh-7 and THP-1 cells. ER stress induced by tunicamycin could clearly be reversed by activating LXRα because it promoted cholesterol efflux by enhancing the expression of ABCA1 and ABCG1 in hepatocytes and macrophages, contributing to attenuation of the development of AS.
Characterization of the expression and prognostic value of 14-3-3 isoforms in breast cancer

The tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation proteins (14-3-3) participate in the tumorigenesis and progression of numerous malignances, but their precise prognostic values in breast cancer (BrCa) remain unknown. Here, we investigated the expression profiles and prognostic roles of 14-3-3 isoforms by employing multiple online databases. The transcriptional levels of most 14-3-3 isoforms in BrCa tissues were significantly higher than those in normal tissues. High mRNA expression of 14-3-3 beta/sigma/theta/zeta was significantly associated with poor overall survival (OS) in BrCa patients, while high mRNA expression of 14-3-3 epsilon was notably related to favorable OS. High mRNA expression of 14-3-3 beta/gamma/sigma/theta/zeta was significantly associated with poor relapse-free survival (RFS) in BrCa patients. A high mutation rate of 14-3-3 was determined to be associated with poor clinical outcomes. In addition, 14-3-3 expression was correlated with the infiltration of specific immune cells types. Analysis of the breast-specific protein-protein interaction (PPI) network suggested that 14-3-3 proteins were involved in several potential oncogenic mechanisms in BrCa. Finally, we performed experimentally validated their oncogenic roles in BrCa. Overall, our findings systematically elucidate the expression and distinct prognostic value of 14-3-3 isoforms in BrCa, which may provide potential therapeutic targets and prognostic biomarkers for BrCa.
Chloroplast Genome Analysis of Two Medicinal Coelogyne spp. (Orchidaceae) Shed Light on the Genetic Information, Comparative Genomics, and Species Identification

Although the medicinal properties of Coelogyne spp. have been previously studied, there is little genomic information providing a valuable tool for the plant taxonomy, conservation, and utilization of this genus. This study used the next-generation MiSeq sequencing platform to characterize the chloroplast (cp) genomes of Coelogyne fimbriata and Coelogyne ovalis. The Maximum Likelihood (ML) and Bayesian (BI) methods were employed to confirm the phylogenetic position of two Coelogyne species based on the whole chloroplast genome sequences. Additionally, we developed eight new primers based on the two cp genomes’ medium variable regions and evaluated the transferability to another 16 Coelogyne species. We constructed phylogenetic trees including 18 Coelogyne species and four outgroup species using the chloroplast fragments with the ML method. Our results showed that the cp genomes of C. fimbriata and C. ovalis contained a small single-copy region (18,839 and 18,851 bp, respectively) and a large single-copy region (87,606 and 87,759 bp, respectively), separated by two same-length inverted-repeat regions (26,675 bp in C. fimbriata and 26,715 bp C. ovalis, respectively). They all contained 86 protein-coding genes, 38 tRNA genes, and eight rRNA genes, revealing strong structure and gene content similarities. The phylogenetic analysis indicated a close relationship between the genera Coelogyne and Pleione. The newly developed primers revealed good transferability among the Coelogyne taxa and provided enough variable sites to distinguish C. fimbriata and C. ovalis. The two complete cp genomes and the eight new primers of Coelogyne provide new genomic data for further studies on phylogenomics, population genetics, and evolutionary history of Coelogyne taxa.
Regulation of microRNA‐221, ‐222, ‐21 and ‐27 in articular cartilage subjected to abnormal compressive forces

microRNAs (miRs) are small non‐coding molecules that regulate post‐transcriptional target gene expression. miRs are involved in regulating cellular activities in response to mechanical loading in all physiological systems, although it is largely unknown whether this response differs with increasing magnitudes of load. miR‐221, miR‐222, miR‐21‐5p and miR‐27a‐5p were significantly increased in ex vivo cartilage explants subjected to increasing load magnitude and in in vivo joint cartilage exposed to abnormal loading. TIMP3 and CPEB3 are putative miR targets in chondrocytes Identification of mechanically regulated miRs that have potential to impact on tissue homeostasis provides a mechanism by which load‐induced tissue behaviour is regulated, in both health and pathology, in all physiological systems.
Beneficial Role of Replacing Dietary Saturated Fatty Acids with Polyunsaturated Fatty Acids in the Prevention of Sarcopenia: Findings from the NU-AGE Cohort

Dietary fat subtypes may play an important role in the regulation of muscle mass and function during ageing. The aim of the present study was to determine the impact of isocaloric macronutrient substitutions, including different fat subtypes, on sarcopenia risk in older men and women, while accounting for physical activity (PA) and metabolic risk. A total of 986 participants, aged 65–79 years, completed a 7-day food record and wore an accelerometer for a week. A continuous sex-specific sarcopenia risk score (SRS), including skeletal muscle mass assessed by dual-energy X-ray absorptiometry (DXA) and handgrip strength, was derived. The impact of the isocaloric replacement of saturated fatty acids (SFAs) by either mono- (MUFAs) or poly-unsaturated (PUFAs) fatty acids on SRS was determined using regression analysis based on the whole sample and stratified by adherence to a recommended protein intake (1.1 g/BW). Isocaloric reduction of SFAs for the benefit of PUFAs was associated with a lower SRS in the whole population, and in those with a protein intake below 1.1 g/BW, after accounting for age, smoking habits, metabolic disturbances, and adherence to PA guidelines. The present study highlighted the potential of promoting healthy diets with optimised fat subtype distribution in the prevention of sarcopenia in older adults.
Evolution of Carotenoid Content, Antioxidant Activity and Volatiles Compounds in Dried Mango Fruits (Mangifera Indica L.)

The aim of this research was to study the evolution of carotenoid compounds, antioxidant β-ctivity, volatiles and sensory quality in two mango cultivars dried at 50, 60 and 70 °C. Total carotenoids in fresh samples were about 12 and 6 mg/100 g (dry basis) in Keitt and Osteen samples, respectively. β-carotene was the main carotenoid, representing about 50% of total carotenoids. In both cultivars, carotenoids were more susceptible to drying at 60 °C. Total phenols and metal reduction activity were higher in Osteen than in Keitt, which had higher values in radical scavenging capacity. The antioxidant activities were best preserved with drying temperatures at 50 °C in Keitt and 60 °C in Osteen fruits. Fresh Osteen mango fruits had a volatile compound content of about 37.1, while Keitt of about 5.2 mg/kg (dry basis). All the compounds with odorous impact were significantly reduced after drying. As regards organoleptic characteristics through sensory analysis, Keitt dried mangoes were quite similar to the fresh product, compared to Osteen.
The Encapsulation of Febuxostat into Emulsomes Strongly Enhances the Cytotoxic Potential of the Drug on HCT 116 Colon Cancer Cells

Febuxostat (FBX) is a drug able to inhibit xanthine oxidase and reduce uric acid production commonly used for the treatment of hyperuricemia in subjects suffering from gout. Several studies have also been directed at its use as anti-cancer drug during the last years, opening a window for its off-label use. In the present study, an optimized formulation in terms of vesicle size and drug release, obtained by encapsulation of FBX into the emulsomes (FBX-EMLs), was evaluated for its cytotoxic potential in human colorectal carcinoma (HCT 116) cells. The optimized FBX-EMLs formula had an improved half maximal inhibitory concentration (IC50), about 4-fold lower, compared to the free drug. The cell cycle analysis showed a significant inhibition of the HCT 116 cells proliferation following FBX-EMLs treatment compared to all the other conditions, with a higher number of cells accumulating on G2/M and pre-G1 phases, paralleled by a significant reduction of cells in G0/G1 and S phases. The optimized formula was also able to significantly increase the percentage of cell population in both early and late stages of apoptosis, characterized by a higher intracellular caspase-3 concentration, as well as percentage of necrotic cells. Lastly, the FBX ability to decrease the mitochondrial membrane potential was enhanced when the drug was delivered into the EMLs. In conclusion, the new formulation of FBX into EMLs improved all the parameters related to the anti-proliferative activity and the toxic potential of the drug towards colorectal cancer cells.
Late-life reproduction in an insect: terminal investment, reproductive restraint or senescence.

1. The Terminal Investment, Reproductive Restraint or Senescence theories may explain individual late-life patterns of reproduction. The terminal investment hypothesis predicts that individuals increase reproductive allocation late in life as prospects for future survival decrease. The other two hypotheses predict reduced reproduction late in life, but for different reasons. Under the Reproductive Restraint hypothesis, individuals restrain their reproductive effort to sustain future survival and gain more time for reproducing, whereas under the Senescence process, reproduction is constrained because of somatic deterioration. While these hypotheses imply that reproduction is costly, they should have contrasted implications in terms of survival after late reproduction and somatic maintenance. 2. Testing these hypotheses requires proper consideration of the effects of age-dependent reproductive effort on post-reproduction survival and age-related somatic functions. We experimentally tested these three hypotheses in females of the mealworm beetle, Tenebrio molitor, an iteroparous and income breeder insect. We manipulated their age-specific allocation into reproduction and observed the effects of this manipulation on their late life- fecundity, post-reproduction survival and immunocompetence as a measurement of somatic protection. 3. We found that females exhibit age-related declines in fecundity and that this reproductive senescence is accelerated by a cost of early reproduction. The cost of reproduction had no significant effect on female longevity and their ability to survive a bacterial infection, despite that some immune cells were depleted by reproduction. We found that female post-infection survival deteriorated with age, which could be partly explained by a decline in some immune parameters. Importantly, females did not increase their reproductive effort late in life at the expense of their late-life post-reproduction survival. 4. Late-life reproduction in T. molitor females is senescing and not consistent with a terminal investment strategy. Rather, our results suggest that females allocate resources according to a priority scheme favouring longevity at the expense of reproduction, which is in line with the reproductive restraint hypothesis. 5. Such a priority scheme also shows that a relatively short-lived insect can evolve life history strategies hitherto known only in long-lived animals. This puts in perspective the role of longevity in the evolution of life history strategies.
Deubiquitinase USP18 promotes the progression of pancreatic cancer via enhancing the Notch1-c-Myc axis

The dysregulation of deubiquitinating enzymes (DUBs), which regulate the stability of most cellular proteins, has been implicated in many human diseases, including cancers. Thus, DUBs can be considered potential therapeutic targets for many cancers. However, the role of deubiquitinase ubiquitin-specific protease 18 (USP18) in pancreatic cancer remains unknown. Here, we found that the deubiquitinase ubiquitin-specific protease 18 (USP18) is significantly upregulated in pancreatic cancer and is correlated with a shorter median overall and relapse-free survival. A functional assay demonstrated that overexpression of USP18 resulted in increased proliferation of pancreatic cancer cells. Conversely, these phenomena were reversed after USP18 was silenced in pancreatic cancer cells. Further investigation revealed that USP18 promoted cell progression by increasing c-Myc expression, which has been reported to control pancreatic cancer progression, and our data demonstrated that c-Myc is key for USP18-mediated pancreatic cancer cell progression in vitro and in vivo. Moreover, we found that USP18 promoted pancreatic cancer progression via upregulation of Notch-1-dependent c-Myc. Mechanistically, USP18 interacts with and removes K48-linked ubiquitin chains from Notch1, thereby stabilizing Notch1 and promoting the Notch1-c-Myc pathway. Our work identifies and validates USP18 as a pancreatic cancer oncogene and provides a potential druggable target for this intractable disease.
Social-Emotional Profile of Children with and without Learning Disabilities: The Relationships with Perceived Loneliness, Self-Efficacy and Well-Being

The current study examined whether perceived social support mediated the effects of loneliness and self-efficacy on well-being among students with or without a learning disability (LD). Participants included 834 elementary, middle, and high school students from Israel (29.6% students with LDs) who completed self-report questionnaires. The results of structural equation modeling indicate that social support mediates the indirect effects of age, gender, loneliness and self-efficacy on well-being. In addition, the results show differences between groups, as non-LD girls noted a higher self-efficacy and well-being than boys, and well-being had indirect effects in the non-LD group than in the LD group. These results indicate students with LDs have a unique social-emotional profile that affects their well-being. The study highlights the importance of enhancing self-efficacy and reducing loneliness in order to increase social support, thus predicting positive well-being. Effective and practical educational programs are needed for both groups across age and gender.
Immunotherapy in gastroesophageal cancers: Current state and future directions

While gastroesophageal (GE) cancers are one of the most common cancers worldwide, unfortunately, the mortality remains high. Commonly used treatment options include surgical resection, chemotherapy, radiotherapy, and molecular targeted therapy, which improve survival only minimally; thus, affirming the dire need for exploring alternative strategies to improve patient outcomes. Immunotherapy, which has revolutionized the world of oncology, has somewhat lagged behind in GE malignancies. Tumor-associated microenvironment and regulatory T cells, alongside cell cycle checkpoints, have been proposed by various studies as the mediators of carcinogenesis in GE cancers. Thus, inhibition of each of these could serve as a possible target of treatment. While the approval of pembrolizumab has provided some hope, it is not enough to override the dismal prognosis that this disease confers. Herein, we discuss the prospects of immunotherapy in this variety of cancer.