Miracle-dz/UniFAR-FTUs huggingface dataset:
Ginsenoside Compound K: Insights into Recent Studies on Pharmacokinetics and Health-Promoting Activities

Ginseng (Panax ginseng) is an herb popular for its medicinal and health properties. Compound K (CK) is a secondary ginsenoside biotransformed from major ginsenosides. Compound K is more bioavailable and soluble than its parent ginsenosides and hence of immense importance. The review summarizes health-promoting in vitro and in vivo studies of CK between 2015 and 2020, including hepatoprotective, anti-inflammatory, anti-atherosclerosis, anti-diabetic, anti-cancer, neuroprotective, anti-aging/skin protective, and others. Clinical trial data are minimal and are primarily based on CK-rich fermented ginseng. Besides, numerous preclinical and clinical studies indicating the pharmacokinetic behavior of CK, its parent compound (Rb1), and processed ginseng extracts are also summarized. With the limited evidence available from animal and clinical studies, it can be stated that CK is safe and well-tolerated. However, lower water solubility, membrane permeability, and efflux significantly diminish the efficacy of CK and restrict its clinical application. We found that the use of nanocarriers and cyclodextrin for CK delivery could overcome these limitations as well as improve the health benefits associated with them. However, these derivatives have not been clinically evaluated, thus requiring a safety assessment for human therapy application. Future studies should be aimed at investigating clinical evidence of CK.
Artificial Saliva in Diabetic Xerostomia (ASDIX): Double Blind Trial of Aldiamed® Versus Placebo

Xerostomia is a symptom frequently present in patients with type 1 (T1DM) and type 2 diabetes mellitus (T2DM). In the present trial, the activity of an artificial saliva (aldiamed® spray) in comparison to a placebo spray were used to evaluate the xerostomia and the saliva antioxidant capacity (SAT). Sixty patients of both genders with T1DM or T2DM were randomized into two groups of 30 subjects each. The experiment was a double-blind study approved by the Ethics Committee of the “G. d’Annunzio University” of Chieti and Pescara. Moreover, measurements of the stimulated saliva flow rate and the ultrasonography of the submandibular and parotid glands were performed at both the study time points. The results demonstrated statistically significant differences between the treatments in terms of the xerostomia average score. Specifically, the values were at baseline and after 30 days 2.9 ± 1.31 and 3.0 ± 1.44 and 1.4 ± 1.48 and 2.4 ± 0.99 for aldiamed® spray and the placebo, respectively. Meanwhile, no statistically significant differences were shown between the two groups for the other variables, such as the salivary flow rate, the antioxidant capacity of the saliva, and the ultrasonography of the major salivary glands.
Spectrum of Headaches Associated With SARS‐CoV‐2 Infection: Study of Healthcare Professionals

Background Series of patients with SARS‐CoV‐2 infection report headache in 6%‐15% of cases, although some data suggest that the actual frequency is higher, and that headache is not associated with fever. No study published to date has analyzed the characteristics of headache in these patients. Objective To analyze the characteristics of COVID‐19 related headaches. Methods We conducted a survey of Spaniard healthcare professionals who have been infected by SARS‐CoV‐2 and presented headache during the course of the disease. The survey addressed respondents’ medical history and headache characteristics, and we analyzed the association between both. Results We analyzed the responses of a sample of 112 healthcare professionals. History of migraine was reported by 20/112 (17.9%) of respondents, history of tension‐type headache by 8/112 (7.1%), and history of cluster headache was reported by a single respondent; 82/112(73.2%) of respondents had no history of headache. Headache presented independently of fever, around the third day after symptom onset. The previous history of migraine was associated with a higher frequency of pulsating headache (20% in patients with previous migraine vs 4.3% in those with no history of migraine, P = .013). Conclusion Headache is often holocranial, hemicranial, or occipital, pressing, and worsens with physical activity or head movements. Because the characteristics of the headache and the associated symptoms are heterogeneous in our survey, we suggest that several patterns with specific pathophysiological mechanisms may underlie the headache associated with COVID‐19.
The role of wood anatomy in phylogeny reconstruction of Ericales

The systematic significance of wood anatomical characters within Ericales is evaluated using separate and combined parsimony analyses including 23 wood characters and 3945 informative molecular characters. Analyses of wood features alone result in poorly resolved and conflicting topologies. However, when pedomorphic character states are coded as inapplicable, the combined bootstrap topology results in an increase of resolution and support at most deeper nodes compared with the molecular analyses. This suggests that phylogenetic information from the limited number of morphological characters is not completely swamped by an overwhelming amount of molecular data. Based on the morphology of vessels and fibers, and the distribution of axial parenchyma, two major wood types can be distinguished within Ericales: (i) a “primitive” type, nearly identical to the wood structure in the more basal outgroup Cornales, which is likely to have persisted in one major clade, and (ii) a “derived” type that must have evolved in at least two separate evolutionary lines. The occurrence of the first type is strongly correlated with shrubs to small trees growing in cold temperate or tropical montane regions, while the second type is common in tall trees of tropical lowlands. This favors the inclusion of ecologically adaptive features in phylogeny reconstruction.
Culturally Tailored Evidence-based Substance Use Disorder Treatments are Efficacious with an American Indian Southwest Tribe: An Open-label Pilot-feasibility Randomized Controlled Trial.

BACKGROUND AND AIMS Many evidence-based treatments (EBTs) for substance use disorder (SUD) exist, yet few are tailored to Indigenous patients. This trial tested the efficacy of a culturally tailored EBT that combined motivational interviewing and the Community Reinforcement Approach (MICRA) versus Treatment as Usual (TAU). DESIGN A mixed efficacy/effectiveness randomized controlled trial of MICRA (n=38) and TAU (n=41) using a parallel design with follow-up assessments at 4, 8, and 12 months post baseline. SETTING United States, reservation-based outpatient, addiction specialty care treatment program. PARTICIPANTS 79 (68% male) American Indian and Alaska Native (AI/AN) Tribal members meeting criteria for SUD and seeking SUD treatment. INTERVENTIONS MICRA (individual therapy sessions beginning with MI for 2 to 3 sessions) compared with TAU (individual and group counseling sessions in a didactic style with Twelve-Step philosophy and elements of relapse prevention). MEASURES Demographics, percent days abstinent (PDA; the primary outcome at 12 months assessed by Form 90D), Inventory of Drug Use Consequences, Alcohol and Drug Use Self-Efficacy Scale, Native American Spirituality Scale, and SCID-DSM-IV-TR. FINDINGS There was no evidence for the benefit of MICRA over TAU (MICRA PDA=72.63%, TAU=73.62%, treatment effect: B: -4.04 (SE=5.47); 95% CI: -14.941, 6.866; BF=3.44) in the primary outcome. Both groups showed improvements in PDA, SUD severity, and negative consequences from baseline to the 12-month follow-up. Neither self-efficacy nor spirituality were significant mediators of MICRA. CONCLUSIONS There were no treatment group differences between culturally tailored evidence-based treatments for substance use disorder and treatment as usual in this randomized controlled trial with American Indian and Alaska Native participants. Nonetheless, participants improved over time on several substance-related outcomes.
Inhibition of p90 ribosomal S6 kinase potentiates cisplatin activity in A549 human lung adenocarcinoma cells

Cisplatin is a standard treatment approach against lung adenocarcinoma. Resistance to cisplatin and the toxic side effects of cisplatin continue to remain a challenge. Combining drugs with different mechanisms is being investigated as a means to overcome these challenges. In ovarian cancer cells, the knockdown of RSK2 increased the sensitivity of cisplatin. RSK is a downstream mediator of the MAPK pathway that is responsible for cell survival, proliferation and migration.
OsNRAMP1 contributes to cadmium and manganese uptake in rice.

Rice is a major dietary source of the toxic metal cadmium (Cd). Previous studies reported that the rice OsNRAMP1 (Natural Resistance-Associated Macrophage Protein 1) could transport iron (Fe), Cd and arsenic (As) in heterologous yeast assays. However, the in planta function of OsNRAMP1 remains unknown. Here, we showed that OsNRAMP1 was able to transport Cd and manganese (Mn) when expressed in yeast, but did not transport Fe or As. OsNRAMP1 was mainly expressed in roots and leaves and encoded a plasma membrane-localized protein. OsNRAMP1 expression was induced by Cd treatment and Fe deficiency. Immunostaining showed that OsNRAMP1 was localized in all root cells except the central vasculature, and in leaf mesophyll cells. The knockout of OsNRAMP1 resulted in significant decreases in root uptake of Cd and Mn and their accumulation in rice shoots and grains, and increased sensitivity to Mn deficiency. The knockout of OsNRAMP1 had smaller effects on Cd and Mn uptake than knockout of OsNRAMP5, while knockout of both genes resulted in large decreases in the uptake of the two metals. Taken together, OsNRAMP1 contributes significantly to the uptake of Mn and Cd in rice and the functions of OsNRAMP1 and OsNRAMP5 are similar but not redundant. This article is protected by copyright. All rights reserved.
Effect of silicon and potassium on tomato anthracnose and on the postharvest quality of tomato fruit (Lycopersicon esculentum Mill.)

The resistance against anthracnose was investigated in tomato cutivars ‘Thilina’ and ‘Maheshi’ by soil application of silicon (Si) at 0 (control), 50 and 100 mg/L during the growth stage, flowering stage and both growth and flowering stages. It showed a reduction of lesions by 80 % in ‘Maheshi’ and 87 % in ‘Thilina’, respectively compared to the control irrespective of the cultivar and stage of the plant at which the treatment was given. Application of potassium (K) at twice (X2) and thrice (X3) the recommended dose to the plants reduced lesion size by over 30 % or 85 % in ‘Thilina’ and ‘Maheshi’ cultivars, respectively. In ‘Maheshi, Si applied at 50 and 100 mg/L at all stages showed a significantly higher (p ≤ 0.05) fruit size compared to the control. Plants treated with higher doses (X2 and X3) of K also showed significantly higher fruit sizes compared to the control. Fruit firmness significantly increased in ‘Maheshi’ treated with 50 and 100 mg/L Si applied at the growth or flowering stage. A significantly lower percentage of total acidity (TA %) was observed in ‘Thilina’ treated with 50 or 100 mg/L Si irrespective of the stage of plant. ‘Thilina’ treated with X2 or X3 doses of K showed significantly higher (p ≤ 0.05) total soluble solid (TSS). Also, the percentage number of appressoria formed (number of spores with appressoria/total number of spores × 100) on areas inoculated with the fungus were significantly higher in fruits treated with X3 K dose and all Si treated fruits compared to the control. J.Natn. Sci.Foundation Sri Lanka 2015 43 (3):273-280
Targeting tumor-associated macrophages and granulocytic-myeloid-derived suppressor cells augments pd-1 blockade in cholangiocarcinoma.

Immune checkpoint blockade (ICB) has revolutionized cancer therapeutics. Desmoplastic malignancies such as cholangiocarcinoma (CCA) have an abundant tumor immune microenvironment (TIME). However, to date ICB monotherapy in such malignancies has been ineffective. Herein, we identify that tumor-associated macrophages (TAMs) are the primary source of PD-L1 in human and murine CCA. In a murine model of CCA, recruited PD-L1+ TAMs facilitate CCA progression. However, TAM blockade failed to decrease tumor progression due to a compensatory emergence of granulocytic-myeloid-derived suppressor cells (G-MDSCs) that mediated immune escape by impairing T-cell response. Single-cell RNA sequencing (scRNA-seq) of murine tumor G-MDSCs highlighted a novel ApoE G-MDSC subset enriched with TAM blockade; further analysis of a human scRNA-seq dataset demonstrated the presence of a similar G-MDSC subset in human CCA. Finally, dual inhibition of TAMs and G-MDSCs potentiated ICB. In summary, our findings highlight the therapeutic potential of coupling ICB with immunotherapies targeting immunosuppressive myeloid cells in CCA.
Hantavirus infection in type I interferon receptor-deficient (A129) mice

Type I interferon receptor knockout mice (strain A129) were assessed as a disease model of hantavirus infection. A range of infection routes (intramuscular, intraperitoneal and intranasal) were assessed using minimally passaged Seoul virus (strain Humber). Dissemination of virus to the spleen, kidney and lung was observed at 5 days after intramuscular and intraperitoneal challenge, which was resolved by day 14. In contrast, intranasal challenge of A129 mice demonstrated virus tropism to the lung, which was maintained to day 14 post-challenge. These data support the use of the A129 mouse model for future infection studies and the in vivo evaluation of interventions.
The earliest known longhorn beetle (Cerambycidae: Prioninae) and implications for the early evolution of Chrysomeloidea

Mesozoic fossils of longhorn beetles, leaf beetles and other Chrysomeloidea are extremely rare, and little is known about the early evolutionary history of this extraordinarily diverse superfamily of beetles. Here we report the earliest known fossil cerambycid, Cretoprionus liutiaogouensis gen. et sp. nov., from the Lower Cretaceous Yixian Formation of China. C. liutiaogouensis bears several features characteristic of the extant subfamily Prioninae, including a large and robust body, absence of a stridulatory plate on the mesonotum, pseudotetramerous tarsi, mouthparts projecting forwards, and lateral carinae on the prothorax. It represents the only definite Mesozoic record of Cerambycidae, and extends the time of origin of the Prioninae as early as the Early Cretaceous. We incorporate two new calibration points as minimum constraints on the age of (1) Prioninae + Parandrinae and (2) Bruchinae using data from a recent molecular phylogenetic study of Chrysomeloidea, to reconstruct divergence times among the major lineages of Chrysomeloidea. Our analyses suggest that most chrysomeloid families appeared in the Jurassic and diversified over the course of the Cretaceous, a scenario consistent with the codiversification of Chrysomeloidea and their (predominantly) angiospermous hosts; however, the phylogeny of Chrysomeloidea remains incompletely resolved, and further elucidation of timing and patterns of chrysomeloid macroevolution will require additional study. http://zoobank.org/urn:lsid:zoobank.org:pub:0FF28F2E-026E-4408-9CF6-D61B6197548E
Macrophage Long Non-Coding RNAs in Pathogenesis of Cardiovascular Disease

Chronic inflammation is inextricably linked to cardiovascular disease (CVD). Macrophages themselves play important roles in atherosclerosis, as well as acute and chronic heart failure. Although the role of macrophages in CVD pathophysiology is well-recognized, little is known regarding the precise mechanisms influencing their function in these contexts. Long non-coding RNAs (lncRNAs) have emerged as significant regulators of macrophage function; as such, there is rising interest in understanding how these nucleic acids influence macrophage signaling, cell fate decisions, and activity in health and disease. In this review, we summarize current knowledge regarding lncRNAs in directing various aspects of macrophage function in CVD. These include foam cell formation, Toll-like receptor (TLR) and NF-kβ signaling, and macrophage phenotype switching. This review will provide a comprehensive understanding concerning previous, ongoing, and future studies of lncRNAs in macrophage functions and their importance in CVD.
Evaluation of left ventricular function in patients with acute ischaemic stroke using cine cardiovascular magnetic resonance imaging

Heart failure (HF) is frequent in patients with acute ischaemic stroke (AIS) and associated with higher morbidity and mortality. Assessment of cardiac function in AIS patients using cardiovascular MRI (CMR) may help to detect HF. We report the rate of systolic and diastolic dysfunction in a cohort of patients with AIS using CMR and compare cine real‐time (CRT) sequences with the reference of segmented cine steady‐state free precession sequences.
Rates of Cutaneous Evaporative Water Loss of Native Fijian Frogs

Abstract Rates of evaporative water loss (EWL) and cutaneous resistance (Rc) to water flux were measured for the two native frog species from the Fiji Islands: the Fiji Ground Frog, Platymantis vitianus, and the Fiji Tree Frog, Platymantis vitiensis (Anura: Ranidae). Surface area specific evaporative water loss was similar between the species: 10.2 (± 1.7) and 9.0 (± 1.7) mg cm−2 h−1 for P. vitiensis and P. vitianus, respectively. The total resistance (Rt) to water loss did not differ from estimates of similarly sized and shaped agar models (representative of a free water surface) for either species; thus, native Fijian frogs are “typical” anurans that have negligible cutaneous resistance (Rc) to EWL. Platymantis vitiensis is apparently able to exploit an arboreal habit, despite the concomitant increase in desiccating conditions, because of the humid environment of the Fiji Islands and by living near streams and rivers.
Nutritional enrichment increases courtship intensity and improves mating success in male spiders

The development of male sexual ornaments and the intensity of male courtship behavior are often used by females as criteria for mate choice and by other males to evaluate the strength of a rival. We tested the hypotheses that courtship intensity and mating success depend on the males' nutritional status (enriched or deficient) and that courtship intensity predicts mating success in males of the same nutritional status. We used wolf spiders, Pardosa prativaga, which have an elaborate display of courtship behaviors, including encircling, palp vibrations, abdomen vibrations, hopping, etc. Viability parameters indicated enhanced condition of enriched males. Mating success was higher for nutrient-enriched males in direct competition with deficient males. Enriched males had higher courtship intensity and were also larger (carapace width) but not heavier than deficient males. The statistical analysis indicated that diet effects on courtship intensity were indirect, through its effect on size. In competition tests between males of equal mass and the same diet treatment, the previously most active male (high levels of palp vibrating, abdomen vibrating, and hopping) had the highest mating success, though this result depended on male nutrient status. The widely used residual condition index (RCI) did not distinguish the treatments. It is suggested that the index is unsuitable in a situation of nutritional stress caused by nutrient imbalance. The results underscore the importance of nutrient balancing to all aspects of performance also in predatory animals. Copyright 2009, Oxford University Press.
Cervus and cucumis peptides combined umbilical cord mesenchymal stem cells therapy for rheumatoid arthritis

Abstract Cervus and cucumis peptides (Lugua polypeptides, LG) are traditional Chinese medicine, which are active components of polypeptide extracted from Sika deer bone and melon seed, and they contain bone induced polypeptide biological factors. Umbilical cord mesenchymal stem cell, (UC-MSC) have tissue repair multiple effects, anti-inflammatory, and immune regulation function, which become a very promising start in rheumatoid arthritis (RA) treatment. Hence, LG combined UC-MSC can significantly enhance the UC-MSC treatment of rheumatoid arthritis (RA). To explore the clinical curative effect and therapeutic mechanism of LG combined UC-MSC for treating RA. 119 patients were divided into control and treatment groups, and both groups were treated with methotrexate tablets, leflunomide, and UC-MSC. But, LG were added to the treatment group. In vitro, the effects of LG on UC-MSC cell secretion of anti-inflammatory factors were also performed. The Health Assessment Questionnaire; the 28 joint disease activity score; C reactive protein; the erythrocyte sedimentation rate; rheumatoid factor; and anti-cyclic citrullinated peptide antibody were significantly reduced in treatment group 1 year after treatment (P < .05). In vitro, compared with the control group, the number of hepatocyte growth factor (HGF), the secretion of prostaglandin E2 (PGE2) and tumor necrosis factor-inducible gene 6 protein (TSG6) increased significantly (P < .05). LG combined UC-MSCs can significantly improve the curative effect of RA patients, while LG may reduce inflammatory cytokines, regulate immunity, improve microcirculation, and are conducive to UC-MSCs migration and the repair of damaged tissue.
NCL Inhibition Exerts Antineoplastic Effects against Prostate Cancer Cells by Modulating Oncogenic MicroRNAs

Prostate cancer (PCa) is the most frequently diagnosed cancer in men and second most common cause of cancer-related deaths in the United States. Androgen deprivation therapy (ADT) is only temporarily effective for advanced-stage PCa, as the disease inevitably progresses to castration-resistant prostate cancer (CRPC). The protein nucleolin (NCL) is overexpressed in several types of human tumors where it is also mislocalized to the cell surface. We previously reported the identification of a single-chain fragment variable (scFv) immuno-agent that is able to bind NCL on the surface of breast cancer cells and inhibit proliferation both in vitro and in vivo. In the present study, we evaluated whether NCL could be a valid therapeutic target for PCa, utilizing DU145, PC3 (CRPC), and LNCaP (androgen-sensitive) cell lines. First, we interrogated the publicly available databases and noted that higher NCL mRNA levels are associated with higher Gleason Scores as well as with recurrent and metastatic tumors. Then, using our anti-NCL scFv, we demonstrated that NCL is expressed on the surface of all three tested cell lines and that NCL inhibition results in reduced proliferation and migration. We also measured the inhibitory effect of NCL targeting on the biogenesis of oncogenic microRNAs such as miR-21, -221 and -222, which was cell context dependent. Taken together, our data provide evidence that NCL targeting inhibits the key hallmarks of malignancy in PCa cells and may provide a novel therapeutic option for patients with advanced-stage PCa.