Miracle-dz/UniFAR-FTUs huggingface dataset:
The Possible Role of Non-Structural Carbohydrates in the Regulation of Tree Hydraulics

The xylem is a complex system that includes a network of dead conduits ensuring long-distance water transport in plants. Under ongoing climate changes, xylem embolism is a major and recurrent cause of drought-induced tree mortality. Non-structural carbohydrates (NSC) play key roles in plant responses to drought and frost stress, and several studies putatively suggest their involvement in the regulation of xylem water transport. However, a clear picture on the roles of NSCs in plant hydraulics has not been drawn to date. We summarize the current knowledge on the involvement of NSCs during embolism formation and subsequent hydraulic recovery. Under drought, sugars are generally accumulated in xylem parenchyma and in xylem sap. At drought-relief, xylem functionality is putatively restored in an osmotically driven process involving wood parenchyma, xylem sap and phloem compartments. By analyzing the published data on stem hydraulics and NSC contents under drought/frost stress and subsequent stress relief, we found that embolism build-up positively correlated to stem NSC depletion, and that the magnitude of post-stress hydraulic recovery positively correlated to consumption of soluble sugars. These findings suggest a close relationship between hydraulics and carbohydrate dynamics. We call for more experiments on hydraulic and NSC dynamics in controlled and field conditions.
The use of back propagation neural networks and 18F-Florbetapir PET for early detection of Alzheimer’s disease using Alzheimer’s Disease Neuroimaging Initiative database

Amyloid beta (Aβ) plaques aggregation is considered as the “start” of the degenerative process that manifests years before the clinical symptoms appear in Alzheimer’s Disease (AD). The aim of this study is to use back propagation neural networks (BPNNs) in 18F-florbetapir PET data for automated classification of four patient groups including AD, late mild cognitive impairment (LMCI), early mild cognitive impairment (EMCI), and significant memory concern (SMC), versus normal control (NC) for early AD detection. Five hundred images for AD, LMCI, EMCI, SMC, and NC, i.e., 100 images for each group, were used from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. The results showed that the automated classification of NC/AD produced a high accuracy of 87.9%, while the results for the prodromal stages of the disease were 66.4%, 60.0%, and 52.9% for NC/LCMI, NC/EMCI and NC/SMC, respectively. The proposed method together with the image preparation steps can be used for early AD detection and classification with high accuracy using Aβ PET dataset.
Sub-Bandgap Photonic Gated-Diode Method for Extracting the Distribution of Hot-Carrier-Induced Interface States in MOSFETs

A sub-bandgap photonic gated-diode method was applied to comparatively extract the energydependent, spatial distributions of traps at the SiO2/Si heterojunction interface in MOSFETs before and after electrical stress. The sub-bandgap photonic gated-diode method was also applied to investigate the interface states (Dit, Nit) and the oxide (Qox) trap distributions caused by the channel’s hot carrier injection with electrical overstress in an n-MOSFET. An optical source with a sub-bandgap energy less than the silicon bandgap energy (Eph = 0.95 eV < Eg = 1.12 eV) was employed for the photonic characterization of the interface states (Eit) distributed within the photo-responsive energy band (EC 0.95 ≤ Eit ≤ EC) in MOS systems. We obtained Dit,max = 2.5 × 10 [1/(cmeV)], Nit,max = 1.65 × 10 [1/cm], and Qox,max = 1.18 × 10 [q/cm]. Through experimental observations with electrical overstress for hot-carrier injection, we observed that the reliability of MOSFETs was dominated more by the interface states than by the oxide trapped charges.
On ATG4B as Drug Target for Treatment of Solid Tumours—The Knowns and the Unknowns

Autophagy is an evolutionary conserved stress survival pathway that has been shown to play an important role in the initiation, progression, and metastasis of multiple cancers; however, little progress has been made to date in translation of basic research to clinical application. This is partially due to an incomplete understanding of the role of autophagy in the different stages of cancer, and also to an incomplete assessment of potential drug targets in the autophagy pathway. While drug discovery efforts are on-going to target enzymes involved in the initiation phase of the autophagosome, e.g., unc51-like autophagy activating kinase (ULK)1/2, vacuolar protein sorting 34 (Vps34), and autophagy-related (ATG)7, we propose that the cysteine protease ATG4B is a bona fide drug target for the development of anti-cancer treatments. In this review, we highlight some of the recent advances in our understanding of the role of ATG4B in autophagy and its relevance to cancer, and perform a critical evaluation of ATG4B as a druggable cancer target.
HHV-6A Infection and Systemic Sclerosis: Clues of a Possible Association

Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, excessive extracellular matrix deposition, and fibrosis of the skin and internal organs. Several infectious agents, including human herpesvirus-6 (HHV-6), have been suggested as possible triggering factors, but a direct association is still missing. We characterized 26 SSc patients for the presence of HHV-6 in tissues and blood, the anti-HHV-6 response, HLA-G plasma levels, and KIR typing. Given the prominent role of endothelial cells (EC) in SSc pathogenesis, along with HHV-6 tropism for EC, we also investigated the expression of pro-fibrosis factors in HHV-6 infected EC. Results showed the presence of HHV-6A in skin biopsies, and an increased virus load was associated with disease severity and poor natural killer (NK) response against the virus, particularly in subjects exhibiting a KIR2 phenotype. HLA-G plasma levels were significantly higher in HHV-6A/B-KIR2 positive SSc patients and in vitro HHV-6A infection-induced pro-fibrosis factors expression in EC, supporting its role in the development of the fibrosing process. Our data suggest an association between virus infection/reactivation and disease, opening the way to future studies to understand the mechanisms by which HHV-6A might contribute to the multifactorial pathogenesis of SSc.
Diet of the brown bear in Himalaya: Combining classical and molecular genetic techniques

The ecological requirements of brown bears are poorly known in the Himalaya region, which complicates conservation efforts. We documented the diet of the Himalayan brown bear (Ursus arctos isabellinus) by combining classical scat analysis and a newly developed molecular genetic technique (the trnL approach), in Deosai National Park, Pakistan. Brown bears consumed over 50 plant species, invertebrates, ungulates, and several rodents. Eight plant families; Poaceae, Polygonaceae, Cyperaceae, Apiaceae, Asteraceae, Caryophyllaceae, Lamiaceae, and Rubiaceae were commonly eaten with graminoids comprising the bulk of the diet. Golden marmots comprised the major mammalian biomass in the park, and were also the main meat source for bears. Animal matter, making 36% of dietary content, contributed half of the digestible energy, due to its higher nutritious value. We did not find a significant temporal pattern in diet, perhaps because the availability of the major diet (graminoids) did not change over the foraging period. Male brown bears were more carnivorous than females, probably because of their larger size, which requires higher energy and also makes them more efficient in capturing marmots. Frequencies of three plant species were also significantly higher in male brown bears; Bistorta affinis, Carex diluta, and Carex sp. Diet of the brown bear differed significantly between the park and surrounding valleys. In valleys, diet consisted predominantly of graminoids and crops, whereas the park provided more nutritious and diverse foodThe estimated digestible energy available to brown bears in Deosai was the lowest documented among brown bear populations, due to the lack of fruits and a relatively lower meat content. The low nutritious diet and high cost of metabolism in a high-altitude environment, probably explains the very low reproductive potential of this population.
Anticancer Effect of Metformin in Herceptin-Conjugated Liposome for Breast Cancer

Metformin (MET) is an anti-diabetic drug effective against breast cancer, targeting breast cancer stem cells (BCSCs). MET-encapsulating liposome (LP-MET) and Herceptin-conjugated LP-MET (Her-LP-MET) were evaluated for their anti-cancer effect in vitro and in vivo. Size and zeta potentials of LP-MET and Her-LP-MET were suitable for enhanced permeability and retention effects. Her-LP-MET yielded greater inhibition of BCSC proliferation in vitro than free MET or LP-MET, as well as a dose-dependent long-term anti-proliferation effect. Further, the anti-migration effect of Her-LP-MET on BCSCs was superior to that of MET or LP-MET, and was enhanced when used in concert with doxorubicin (DOX). In a mouse model, Her-LP-MET combined with free DOX was more effective than free MET, free DOX, or Her-LP-MET. Moreover, Her-LP-MET combined with free DOX yielded tumor remission, whereas free DOX alone resulted in metastasis or death. As such, Her-LP-MET formulation is expected to provide a new therapeutic modality targeting BCSCs.
Rac1 Inhibition Via Srgap2 Restrains Inflammatory Osteoclastogenesis and Limits the Clastokine, SLIT3

The Rac1‐specific guanosine triphosphatase (GTPase)‐activating protein Slit‐Robo GAP2 (Srgap2) is dramatically upregulated during RANKL‐induced osteoclastogenesis. Srgap2 interacts with the cell membrane to locally inhibit activity of Rac1. In this study, we determined the role of Srgap2 in the myeloid lineage on bone homeostasis and the osteoclastic response to TNFα treatment. The bone phenotype of mice specifically lacking Srgap2 in the myeloid lineage (Srgap2 f/f:LysM‐Cre; Srgap2 conditional knockout [cKO]) was investigated using histomorphometric analysis, in vitro cultures and Western blot analysis. Similar methods were used to determine the impact of TNFα challenge on osteoclast formation in Srgap2 cKO mice. Bone parameters in male Srgap2 cKO mice were unaffected. However, female cKO mice displayed higher trabecular bone volume due to increased osteoblast surface and bone formation rate, whereas osteoclastic parameters were unaltered. In vitro, cells from Srgap2 cKO had strongly enhanced Rac1 activation, but RANKL‐induced osteoclast formation was unaffected. In contrast, conditioned medium from Srgap2 cKO osteoclasts promoted osteoblast differentiation and had increased levels of the bone anabolic clastokine SLIT3, providing a possible mechanism for increased bone formation in vivo. Rac1 is rapidly activated by the inflammatory cytokine TNFα. Supracalvarial injection of TNFα caused an augmented osteoclastic response in Srgap2 cKO mice. In vitro, cells from Srgap2 cKO mice displayed increased osteoclast formation in response to TNFα. We conclude that Srgap2 plays a prominent role in limiting osteoclastogenesis during inflammation through Rac1, and restricts expression of the paracrine clastokine SLIT3, a positive regulator of bone formation. © 2019 American Society for Bone and Mineral Research.
Earth's Impact Events Through Geologic Time: A List of Recommended Ages for Terrestrial Impact Structures and Deposits

This article presents a current (as of September 2019) list of recommended ages for proven terrestrial impact structures (n = 200) and deposits (n = 46) sourced from the primary literature. High-precision impact ages can be used to (1) reconstruct and quantify the impact flux in the inner Solar System and, in particular, the Earth–Moon system, thereby placing constraints on the delivery of extraterrestrial mass accreted on Earth through geologic time; (2) utilize impact ejecta as event markers in the stratigraphic record and to refine bio- and magneto-stratigraphy; (3) test models and hypotheses of synchronous double or multiple impact events in the terrestrial record; (4) assess the potential link between large impacts, mass extinctions, and diversification events in the biosphere; and (5) constrain the duration of melt sheet crystallization in large impact basins and the lifetime of hydrothermal systems in cooling impact craters, which may have served as habitats for microbial life on the early Earth and, possibly, Mars.
An Ustilago maydis chassis for itaconic acid production without by‐products

Ustilago maydis is a promising yeast for the production of a range of valuable metabolites, including itaconate, malate, glycolipids and triacylglycerols. However, wild‐type strains generally produce a potpourri of all of these metabolites, which hinders efficient production of single target chemicals. In this study, the diverse by‐product spectrum of U. maydis was reduced through strain engineering using CRISPR/Cas9 and FLP/FRT, greatly increasing the metabolic flux into the targeted itaconate biosynthesis pathway. With this strategy, a marker‐free chassis strain could be engineered, which produces itaconate from glucose with significantly enhanced titre, rate and yield. The lack of by‐product formation not only benefited itaconate production, it also increases the efficiency of downstream processing improving cell handling and product purity.
Influence of Climate and Local Habitat Characteristics on Carabid Beetle Abundance and Diversity in Northern Chinese Steppes

Carabids are an important insect group in grassland ecosystems and are involved in numerous ecosystem services. Steppes are the most widespread ecosystems in China, but they are under increasing degradation. Despite their importance, little is known about the relationships between environmental variables and carabid community structure in Chinese steppes. We studied the effects of fine-scale factors (soil and vegetation) and coarse-scale factors (climate) on carabid community parameters (abundance, richness, diversity, dominance, and evenness) in three types of steppes (desert, typical, and meadow steppes) in northern China. Carabid communities responded to environmental factors in different ways according to the type of steppe. Climate factors were the most important drivers of community structure, whereas the effects of soil and vegetation were less important. Desert steppe showed the lowest carabid abundance, richness, diversity, and evenness, and the highest dominance. This community is relatively simple and strongly dominated by a few species adapted to the severe conditions of this environment. Typical and meadow steppes showed carabid communities with a more complex structure. As expected on the basis of environmental severity, the most severe ecosystem (i.e., the desert) was only influenced by climatic factors, whereas a certain influence of biotic factors emerged in the other ecosystems.
Efficacy of Recombinant Human Epidermal Growth Factor (Regen-D 150) in Healing Diabetic Foot Ulcers: A Hospital-Based Randomized Controlled Trial

To validate the efficacy of recombinant human epidermal growth factor (hEGH) in healing diabetic foot ulcers (DFUs) at biochemical and molecular levels. A total of 50 noninfected DFU subjects were recruited for the study and divided into 2 groups based on the treatment application on the subjects. Group 1: DFU subjects treated with hEGH gel-based product called Regen-D 150 (n = 27) and group 2: DFU subjects treated with alternative placebo as the control group (n = 23). Patients were observed for 30 days and punch biopsy was taken at days 0 and 14. Histologic analysis was done to study the matrix alignment, cellular infiltration, and differentiation of epithelial layers. Biochemical analysis was done to quantitatively estimate the amount of collagen and proteoglycans regenerated in the wound area. Complete healing of ulcers was observed in 21 (78%) subjects in group 1, whereas only 12 (52%) subjects among group 2 reported of complete healing of ulcer after completion of the study period of 30 days. Collagen and fibroblasts were significantly developed in group 1 when observed in the follow-up samples. Healing time of the wound among the group 1 subjects was significantly less than the group 2 subjects (45 ± 12 vs 72 ± 18 days, P < .0001) and even showed a better blood glucose level. Early and regular application of the hEGH on DFUs will lead to prevention of leg amputations and would serve to act as a major treatment therapy for healing of chronic wounds.
Multidisciplinary Care for Cystic Fibrosis Liver Disease: Where Does the Adult Hepatologist Fit In?

Cystic fibrosis (CF) is the most common inherited genetic disorder in Caucasians and is caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CF is a multisystem disease, and an estimated 9.5% of patients with CF have hepatobiliary complications. Improved care for the pulmonary manifestations of the disease has improved life expectancy dramatically from a median predicted survival age of 30 years in 1986 to 46.2 years in 2017. In light of this increasing life span, cystic fibrosis–related liver disease (CFLD) is increasingly recognized and is now the third most common cause of mortality in this patient population. Even though CFLD most commonly presents in childhood and progresses into adulthood, adult-onset CFLD has recently been described. Multidisciplinary team–based care for patients with CF at dedicated CF centers is considered standard of care. CF centers are directed by a physician with considerable CF experience supported by dedicated CF nurses, psychologists, social workers, pharmacists, and dieticians. It is also recommended that CF centers have close links to other consultants, including those specializing in gastroenterology and hepatology. Taking this one step further, European CF guidelines recommend annual screening and evaluation for CFLD by a gastroenterologist. In the United States, the Cystic Fibrosis Foundation has recognized the growing demand for physicians focusing on the gastrointestinal and hepatobiliary manifestations of the disease, and has created the Developing Innovative Gastroenterology Specialty Training program to encourage specialty training and research in the field. Although a number of CF centers include a gastroenterologist and/or hepatologist among their multidisciplinary staff, data assessing the effects of
Graphene Quantum Dot-Based Electrochemical Immunosensors for Biomedical Applications

In the area of biomedicine, research for designing electrochemical sensors has evolved over the past decade, since it is crucial to selectively quantify biomarkers or pathogens in clinical samples for the efficacious diagnosis and/or treatment of various diseases. To fulfil the demand of rapid, specific, economic, and easy detection of such biomolecules in ultralow amounts, numerous nanomaterials have been explored to effectively enhance the sensitivity, selectivity, and reproducibility of immunosensors. Graphene quantum dots (GQDs) have garnered tremendous attention in immunosensor development, owing to their special attributes such as large surface area, excellent biocompatibility, quantum confinement, edge effects, and abundant sites for chemical modification. Besides these distinct features, GQDs acquire peroxidase (POD)-mimicking electro-catalytic activity, and hence, they can replace horseradish peroxidase (HRP)-based systems to conduct facile, quick, and inexpensive label-free immunoassays. The chief motive of this review article is to summarize and focus on the recent advances in GQD-based electrochemical immunosensors for the early and rapid detection of cancer, cardiovascular disorders, and pathogenic diseases. Moreover, the underlying principles of electrochemical immunosensing techniques are also highlighted. These GQD immunosensors are ubiquitous in biomedical diagnosis and conducive for miniaturization, encouraging low-cost disease diagnostics in developing nations using point-of-care testing (POCT) and similar allusive techniques.
Phenolic Profile, Antioxidant and Anti-Proliferative Activities of Methanolic Extracts from Asclepias linaria Cav. Leaves

Asclepias linaria Cav. (Apocynaceae) is a shrubby plant endemic of Mexico which has been used in traditional medicine. However, the bioactive potential of this plant remains unexplored. In this study, the phenolic composition, antioxidant, and cytotoxic activities of A. linaria leaves were determined. In order to estimate the phenolic composition of the leaves, the total phenolic, flavonoid, and condensed tannins contents were determined. Furthermore, the antioxidant activity was measured by the scavenging activity of the 2,2-diphenyl-1-picrylhydrazyl (DPPH•) and 2,2′-azino-bis[3-ethylbenzothiazoline-6-sulphonic acid] (ABTS•+) radicals and the total antioxidant capacity. The phenolic compounds identified in the A. linaria leaves by ultra-performance liquid chromatography coupled to mass spectrometry (UPLC-MS) include phenolic acids, such as p-coumaric and ferulic acid, as well as flavonoids, such as rutin and quercetin. The leaves’ extracts of A. linaria showed a high scavenging activity of DPPH• and ABTS•+ radicals (IC50 0.12 ± 0.001 and 0.51 ± 0.003 µg/mL, respectively), high total antioxidant capacity values (99.77 ± 4.32 mg of ascorbic acid equivalents/g of dry tissue), and had a cytotoxic effect against K562 and HL60 hematologic neoplasia cells lines, but no toxicity towards the normal mononuclear cell line was observed. These results highlight the potential of A. linaria and could be considered as a possible alternative source of anticancer compounds.
Awareness of treatment: A source of bias in subjective grading of ocular complications

Purpose Bias has been described as one important obstacle in scientific research. The aim of this study was to explore “awareness of treatment” as a possible source of bias in subjective grading of ocular complications. Methods Thirty subjects with similar, basic experience with grading scales participated in the study. The Efron grading scales were used to grade 24 images of three different ocular conditions (eight images each of bulbar hyperaemia, limbal vascularization and corneal staining). Three consecutive, two weeks apart, grading sessions were scheduled, in which the same images were graded, although in the third session images were deceptively labelled as either “treated” or “untreated”. Grading results from the first and second sessions were compared to determine grading reliability and discrepancies with the third session informed of grading bias originating from “awareness of treatment”. Results Moderate to good test-retest reliability was found for all conditions, with median intraclass correlation values of 0.80 (0.62–0.84) for bulbar hyperaemia, 0.68 (0.65–0.77) for limbal vascularization and 0.68 (0.66–0.74) for corneal staining. Grading values from the first and third sessions evidenced negative and positive systematic errors (bias) for “treated” and “untreated” conditions, respectively. Statistically significant differences were found between the average grading discrepancies of session 1 and session 2 and those of session 1 and session 3 (all p<0.001). Conclusions “Awareness of treatment” may be considered a source of bias of subjective grading of ocular complications, although the actual effect of bias is unlikely to be of clinical significance.