Miracle-dz/UniFAR-FTUs huggingface dataset:
The Characteristics of Mercury Flux at the Interfaces between Two Typical Plants and the Air in Leymus chinensis Grasslands

Mercury is a global pollutant. The mercury exchanges between vegetation and the atmosphere are important for the global mercury cycle. Grassland ecosystems occupy more than 25% of the global land area and have different succession processes and ecological functions. The current research regarding mercury exchanges between forests and the atmosphere have attracted much attention, but the research regarding grasslands tends to be rare. To reveal the characteristics of mercury exchanges in grasslands, this study conducted field in-situ monitoring experiments in a Leymus meadow grassland regions of the Songnen Plains in northeastern China. The exchange flux values of the GEM (gaseous element mercury) between the plants and the atmosphere were measured using a dynamic flux bag method (DFB). The experiments were conducted for the purpose of assessing the mercury flux levels between the vegetation and the atmosphere in a typical Leymus chinensis meadow. The goal was to further the understanding of the change characteristics and influential factors and to describe the source and sink actions and dynamics between the grassland vegetation and the atmosphere. The diurnal variation characteristics were as follows: High during the day and low at night, with peaks generally appearing at noon. The growing period was characterized by absorption peaks of atmospheric mercury by the plants. The breeding period was characterized by the peak release of atmospheric mercury by the plants. The change characteristics were as follows: During the growing period, the duration of the plants in a mercury absorption state exceeded 96.5%, which was represented as the net sink of the atmospheric mercury. During the breeding period, the time of mercury release ranged between 46.4% and 66.8%, making the breeding period the net source of atmospheric mercury. The results of this study’s analysis indicated that each environmental factor was correlated with the mercury flux, and the environmental factors had different effects on the mercury flux during the different stages of plant growth. The atmospheric mercury concentration levels were the main factor during the growing period. Atmospheric humidity was the main factor during the breeding period. Solar radiation was the decisive factor during the entire experimental period.
Increased Risk of Chronic Kidney Disease Associated With Weight Gain in Healthy Adults: Insight From Metabolic Profiles and Body Composition

Objective: Obesity is an established risk factor for kidney damage. In this study, we explored the long-term association of changes in body mass index (BMI) over time with incident chronic kidney disease (CKD). Methods: For this analysis, 5,393 middle-aged adults without comorbidities in the Korean Genome and Epidemiology Study (KoGES) were included. Group-based trajectory modeling was used to determine the patterns of BMI change (decreasing, stable, and increasing BMI) between baseline and year 4. The primary outcome was the subsequent development of CKD from year 4. A multivariable Cox proportional hazards model was constructed to determine the risk of incident CKD according to BMI trajectories. Results: During 55,327 person-years, incident CKD occurred in 354 (6.5%) participants; 6.0, 6.1, and 7.8 per 1,000 person-years across the trajectories, respectively (P = 0.005). In the multivariable-adjusted Cox proportional hazards model, the increasing BMI trajectory was associated with a 1.4-fold [hazard ratio (HR), 1.41; 95% CI, 1.06–1.87] a higher risk of incident CKD compared with stable BMI trajectory. This association was stronger for overweight and obese individuals. The HRs for CKD development in these two groups were 1.6 (95% CI, 1.06–1.87) and 2.2 (95% CI, 1.40–3.48), respectively. While the increasing BMI group was gaining weight, there were concomitant increases in blood pressure, insulin resistance, serum concentrations of total cholesterol, triglyceride, and high-sensitivity C-reactive protein (hs-CRP), and fat mass, but high-density lipoprotein (HDL)-cholesterol level and muscle-to-fat (MF) ratio decreased. Conclusion: Weight gain is associated with an increased risk of incident CKD in healthy adults. This association is attributed to worsening metabolic profiles and increasing fat mass.
Bile-Acid-Appended Triazolyl Aryl Ketones: Design, Synthesis, In Vitro Anticancer Activity and Pharmacokinetics in Rats

A library of bile-acid-appended triazolyl aryl ketones was synthesized and characterized by detailed spectroscopic techniques such as 1H and 13C NMR, HRMS and HPLC. All the synthesized conjugates were evaluated for their cytotoxicity at 10 µM against MCF-7 (human breast adenocarcinoma) and 4T1 (mouse mammary carcinoma) cells. In vitro cytotoxicity studies on the synthesized conjugates against MCF-7 and 4T1 cells indicated one of the conjugate 6cf to be most active against both cancer cell lines, with IC50 values of 5.71 µM and 8.71 µM, respectively, as compared to the reference drug docetaxel, possessing IC50 values of 9.46 µM and 13.85 µM, respectively. Interestingly, another compound 6af (IC50 = 2.61 µM) was found to possess pronounced anticancer activity as compared to the reference drug docetaxel (IC50 = 9.46 µM) against MCF-7. In addition, the potent compounds (6cf and 6af) were found to be non-toxic to normal human embryonic kidney cell line (HEK 293), as evident from their cell viability of greater than 86%. Compound 6cf induces higher apoptosis in comparison to 6af (46.09% vs. 33.89%) in MCF-7 cells, while similar apoptotic potential was observed for 6cf and 6af in 4T1 cells. The pharmacokinetics of 6cf in Wistar rats showed an MRT of 8.47 h with a half-life of 5.63 h. Clearly, these results suggest 6cf to be a potential candidate for the development of anticancer agents.
Comparative metabolomics reveals differences in primary and secondary metabolites between “Shixia” and “Chuliang” longan (Dimocarpus longan Lour.) pulp

Abstract Longan was a characteristic fruit for both medicine and food in China, which was rich in primary and secondary metabolites. Comprehensive high‐throughput identification and comparison of metabolites in longan pulp among different varieties were still lacked. “Shixia” (SX) and “Chuliang” (CL) were the biggest major cultivars of longan in China. In this study, the content of total soluble solid, total flavonoid, and total phenolics indicated the difference of sweetness and bioactive compound content between the SX and CL pulp. Through a widely targeted metabolome, a total of 514 metabolites were identified and categorized into 23 groups mainly including flavonoids, amino acids & derivatives, lipids, phenolic acids, nucleotides & derivatives, alkaloids, organic acids and sugars & derivatives. A total of 89 metabolites with significantly differential accumulation (variable importance in projection (VIP) value ≧1, p‐value <. 05) over 1.2 fold were found between SX and CL, which were mainly enriched into pathways including flavone and flavonol biosynthesis, glycolysis/gluconeogenesis, and arginine and proline metabolism. Higher leveled hexose and hexose‐phosphate (i.e., β‐D‐glucose, D(+)‐glucose, glucose‐1‐phosphate and glucose‐6‐phosphate), dominant organic acids (i.e., citric acid, succinic acid, D‐malic acid, and citramalate), and essential amino acids (L‐threonine, L‐valine, L‐isoleucine, L‐leucine, L‐phenylalanine and L‐lysine) in SX pulp might be contributed to the taste and flavor difference between SX and CL. Moreover, the greatly differential accumulated secondary metabolites especially flavonoids and phenolic acids might result in different medicinal and nutritional characteristic between SX and CL. In conclusion, this study provided a systemic metabolic basis for understanding the nutritional differences between SX and CL and would help deepen the molecular biology and pharmacology research on characteristic metabolites in longan pulp.
Cholecystokinin Receptor Antagonist Improves Efficacy of Chemotherapy in Murine Models of Pancreatic Cancer by Altering the Tumor Microenvironment

Simple Summary Our research team has identified the cholecystokinin-B receptor (or CCK-BR) as a novel target for treatment of pancreatic cancer. CCK-BRs are over-expressed in pancreatic cancer and activation stimulates growth in cell culture and in animal models. CCK-BRs are also expressed on pancreatic stellate cells—or the fibroblasts that are responsible for the dense fibrosis in the tumor microenvironment that impedes the penetration of chemotherapy. We show strong evidence that treatment with a CCK receptor antagonist, proglumide, decreases fibrosis in the pancreatic tumor microenvironment and increases the influx of T-cells rendering chemotherapy-resistant cancer, sensitive to gemcitabine. Mice treated with the combination therapy had fewer metastases and greater survival. Tumors from these mice had higher gemcitabine levels and novel differentially expressed genes by RNA-Seq. Proglumide is an older drug that was developed many years ago for peptic ulcer disease but is no longer in use. Repurposing this older drug may improve survival from this recalcitrant malignancy. Abstract Pancreatic cancer is resistant to chemotherapy in part due to the dense desmoplastic fibrosis surrounding the tumor, the immunosuppressive cells in the tumor microenvironment (TME), and the early rate of metastases. In this study, we examined the effects of a CCK receptor antagonist, proglumide, alone and in combination with gemcitabine in murine models of pancreatic cancer. Tumor growth rate, metastases, and survival were assessed in mice bearing syngeneic murine or human pancreatic tumors treated with PBS (control), gemcitabine, proglumide, or the combination of gemcitabine and proglumide. Excised tumors were evaluated histologically for fibrosis, immune cells, molecular markers, and uptake of chemotherapy by mass spectroscopy. Peripheral blood was analyzed with a microRNAs biomarker panel associated with fibrosis and oncogenesis. Differentially expressed genes between tumors of mice treated with gemcitabine monotherapy and combination therapy were compared by RNAseq. When given in combination the two compounds exhibited inhibitory effects by decreasing tumor growth rate by 70%, metastases, and prolonging survival. Proglumide monotherapy altered the TME by decreasing fibrosis, increasing intratumoral CD8+ T-cells, and decreasing arginase-positive cells, thus rendering the tumor sensitive to chemotherapy. Proglumide altered the expression of genes involved in fibrosis, epithelial–mesenchymal transition, and invasion. CCK-receptor antagonism with proglumide renders pancreatic cancer susceptible to chemotherapy.
Diffusion–Based Virtual MR Elastography of the Liver: Can It Be Extended beyond Liver Fibrosis?

Background: Strong correlation has been reported between tissue water diffusivity and tissue elasticity in the liver. The purpose of this study is to explore the capability of diffusion–based virtual MR elastography (VMRE) in the characterization of liver tumors by extending beyond liver fibrosis assessments. Methods: Fifty-four patients (56 liver tumors: hepatocellular carcinoma (HCC), 31; metastases, 25) who underwent MRE, diffusion-weighted imaging (DWI) (b: 0, 800 s/mm2), and VMRE (b: 200, 1500 s/mm2) were enrolled. The MRE shear modulus (µMRE), apparent diffusion coefficient (ADC), and shifted ADC (sADC) were obtained. Virtual stiffness (µdiff) was estimated from the relationship between µMRE and sADC. A linear discriminant analysis combining VMRE and MRE to classify HCC and metastases was performed in a training cohort (thirty-two patients) to estimate a classifier (C), and evaluate its accuracy in a testing cohort (twenty-two patients). Pearson’s correlations between µMRE, sADC, and ADC were evaluated. In addition to the discriminant analysis, a receiver operating characteristic (ROC) curve was used to assess the discrimination capability between HCC and metastases. Results: The correlations between µMRE and sADC were significant for liver, HCC, and metastases (r = 0.91, 0.68, 0.71; all p < 0.05). Those between µMRE and ADC were weaker and significant only for metastases (r = 0.17, 0.20, 0.55). µdiff values were not significantly different between HCC and metastases (p = 0.56). Areas under the curves (AUC) to differentiate HCC from metastases were as follows: VMRE, 0.46; MRE alone, 0.89; MRE + VMRE, 0.96. The classifier C also provided better performance than MRE alone, in terms of sensitivity (100 vs. 93.5%, respectively) and specificity (92 vs. 76%, respectively, p = 0.046). Conclusions: The correlation between sADC and µMRE was strong both in the liver and in tumors. However, VMRE alone could not classify HCC and metastases. The combination of MRE and VMRE, however, allowed discriminant performance between HCC and metastases.
Inflammation and Oxidative Stress in Diabetic Kidney Disease: The Targets for SGLT2 Inhibitors and GLP-1 Receptor Agonists

The incidence of type 2 diabetes (T2D) has been increasing worldwide, and diabetic kidney disease (DKD) remains one of the leading long-term complications of T2D. Several lines of evidence indicate that glucose-lowering agents prevent the onset and progression of DKD in its early stages but are of limited efficacy in later stages of DKD. However, sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor (GLP-1R) agonists were shown to exert nephroprotective effects in patients with established DKD, i.e., those who had a reduced glomerular filtration rate. These effects cannot be solely attributed to the improved metabolic control of diabetes. In our review, we attempted to discuss the interactions of both groups of agents with inflammation and oxidative stress—the key pathways contributing to organ damage in the course of diabetes. SGLT2i and GLP-1R agonists attenuate inflammation and oxidative stress in experimental in vitro and in vivo models of DKD in several ways. In addition, we have described experiments showing the same protective mechanisms as found in DKD in non-diabetic kidney injury models as well as in some tissues and organs other than the kidney. The interaction between both drug groups, inflammation and oxidative stress appears to have a universal mechanism of organ protection in diabetes and other diseases.
Porphyrin–Schiff Base Conjugates Bearing Basic Amino Groups as Antimicrobial Phototherapeutic Agents

New porphyrin–Schiff base conjugates bearing one (6) and two (7) basic amino groups were synthesized by condensation between tetrapyrrolic macrocycle-containing amine functions and 4-(3-(N,N-dimethylamino)propoxy)benzaldehyde. This approach allowed us to easily obtain porphyrins substituted by positive charge precursor groups in aqueous media. These compounds showed the typical Soret and four Q absorption bands with red fluorescence emission (ΦF ~ 0.12) in N,N-dimethylformamide. Porphyrins 6 and 7 photosensitized the generation of O2(1Δg) (ΦΔ ~ 0.44) and the photo-oxidation of L-tryptophan. The decomposition of this amino acid was mainly mediated by a type II photoprocess. Moreover, the addition of KI strongly quenched the photodynamic action through a reaction with O2(1Δg) to produce iodine. The photodynamic inactivation capacity induced by porphyrins 6 and 7 was evaluated in Staphylococcus aureus, Escherichia coli, and Candida albicans. Furthermore, the photoinactivation of these microorganisms was improved using potentiation with iodide anions. These porphyrins containing basic aliphatic amino groups can be protonated in biological systems, which provides an amphiphilic character to the tetrapyrrolic macrocycle. This effect allows one to increase the interaction with the cell wall, thus improving photocytotoxic activity against microorganisms.
Crystalline-Induced Arthropathy Following Total Knee Replacement

Gout rarely occurs in the setting of prior total joint replacement. It can present as an acute or chronic painful joint that may mimic prosthetic joint infection with further similarities found on physical examination and initial workup. Elevated leukocyte count, erythrocyte sedimentation rate, and C-reactive protein are common to both conditions. The confirmatory test to distinguish infection versus inflammatory arthropathy is joint aspiration with crystal or micro-organism identification microscopically. Establishing proper diagnosis is important in guiding appropriate treatment, which may prevent the unnecessary removal of implants. The current study includes a review of the literature and presents a case of bilateral gouty arthropathy after total knee arthroplasty.
MEIS2 Is an Adrenergic Core Regulatory Transcription Factor Involved in Early Initiation of TH-MYCN-Driven Neuroblastoma Formation

Simple Summary Neuroblastoma is a pediatric tumor originating from the sympathetic nervous system responsible for 10–15% of all childhood cancer deaths. Half of all neuroblastoma patients present with high-risk disease, of which nearly 50% relapse and die of their disease. In addition, standard therapies cause serious lifelong side effects and increased risk for secondary tumors. Further research is crucial to better understand the molecular basis of neuroblastomas and to identify novel druggable targets. Neuroblastoma tumorigenesis has to this end been modeled in both mice and zebrafish. Here, we present a detailed dissection of the gene expression patterns that underlie tumor formation in the murine TH-MYCN-driven neuroblastoma model. We identified key factors that are putatively important for neuroblastoma tumor initiation versus tumor progression, pinpointed crucial regulators of the observed expression patterns during neuroblastoma development and scrutinized which factors could be innovative and vulnerable nodes for therapeutic intervention. Abstract Roughly half of all high-risk neuroblastoma patients present with MYCN amplification. The molecular consequences of MYCN overexpression in this aggressive pediatric tumor have been studied for decades, but thus far, our understanding of the early initiating steps of MYCN-driven tumor formation is still enigmatic. We performed a detailed transcriptome landscaping during murine TH-MYCN-driven neuroblastoma tumor formation at different time points. The neuroblastoma dependency factor MEIS2, together with ASCL1, was identified as a candidate tumor-initiating factor and shown to be a novel core regulatory circuit member in adrenergic neuroblastomas. Of further interest, we found a KEOPS complex member (gm6890), implicated in homologous double-strand break repair and telomere maintenance, to be strongly upregulated during tumor formation, as well as the checkpoint adaptor Claspin (CLSPN) and three chromosome 17q loci CBX2, GJC1 and LIMD2. Finally, cross-species master regulator analysis identified FOXM1, together with additional hubs controlling transcriptome profiles of MYCN-driven neuroblastoma. In conclusion, time-resolved transcriptome analysis of early hyperplastic lesions and full-blown MYCN-driven neuroblastomas yielded novel components implicated in both tumor initiation and maintenance, providing putative novel drug targets for MYCN-driven neuroblastoma.
3D-Printed vs. Heat-Polymerizing and Autopolymerizing Denture Base Acrylic Resins

The aim of this work was to investigate the effect of two post-curing methods on the mechanical properties of a 3D-printed denture base material. Additionally, to compare the mechanical properties of that 3D-printed material with those of conventional autopolymerizing and a heat-cured denture base material. A resin for 3D-printing denture base (Imprimo®), a heat-polymerizing acrylic resin (Paladon® 65), and an autopolymerizing acrylic resin (Palapress®) were investigated. Flexural strength, elastic modulus, fracture toughness, work of fracture, water sorption, and water solubility were evaluated. The 3D-printed test specimens were post-cured using two different units (Imprimo Cure® and Form Cure®). The tests were carried out after both dry and 30 days water storage. Data were collected and statistically analyzed. Resin type had a significant effect on the flexural strength, elastic modulus, fracture toughness, and work of fracture (p < 0.001). The flexural strength and elastic modulus for the heat-cured polymer were significantly the highest among all investigated groups regardless of the storage condition (p < 0.001). The fracture toughness and work of fracture of the 3D-printed material were significantly the lowest (p < 0.001). The heat-cured polymer had the lowest significant water solubility (p < 0.001). The post-curing method had an impact on the flexural strength of the investigated 3D-printed denture base material. The flexural strength, elastic modulus, fracture toughness, work of fracture of the 3D-printed material were inferior to those of the heat-cured one. Increased post-curing temperature may enhance the flexural properties of resin monomers used for 3D-printing dental appliances.
Synthetic Retinoids as Potential Therapeutics in Prostate Cancer—An Update of the Last Decade of Research: A Review

Prostate cancer (PC) is the second most common tumor in males. The search for appropriate therapeutic options against advanced PC has been in process for several decades. Especially after cessation of the effectiveness of hormonal therapy (i.e., emergence of castration-resistant PC), PC management options have become scarce and the prognosis is poor. To overcome this stage of disease, an array of natural and synthetic substances underwent investigation. An interesting and promising class of compounds constitutes the derivatives of natural retinoids. Synthesized on the basis of the structure of retinoic acid, they present unique and remarkable properties that warrant their investigation as antitumor drugs. However, there is no up-to-date compilation that consecutively summarizes the current state of knowledge about synthetic retinoids with regard to PC. Therefore, in this review, we present the results of the experimental studies on synthetic retinoids conducted within the last decade. Our primary aim is to highlight the molecular targets of these compounds and to identify their potential promise in the treatment of PC.
Hyperglycemia Altered DNA Methylation Status and Impaired Pancreatic Differentiation from Embryonic Stem Cells

The prevalence of type 2 diabetes (T2D) is rapidly increasing across the globe. Fetal exposure to maternal diabetes was correlated with higher prevalence of impaired glucose tolerance and T2D later in life. Previous studies showed aberrant DNA methylation patterns in pancreas of T2D patients. However, the underlying mechanisms remained largely unknown. We utilized human embryonic stem cells (hESC) as the in vitro model for studying the effects of hyperglycemia on DNA methylome and early pancreatic differentiation. Culture in hyperglycemic conditions disturbed the pancreatic lineage potential of hESC, leading to the downregulation of expression of pancreatic markers PDX1, NKX6−1 and NKX6−2 after in vitro differentiation. Genome-wide DNA methylome profiling revealed over 2000 differentially methylated CpG sites in hESC cultured in hyperglycemic condition when compared with those in control glucose condition. Gene ontology analysis also revealed that the hypermethylated genes were enriched in cell fate commitment. Among them, NKX6−2 was validated and its hypermethylation status was maintained upon differentiation into pancreatic progenitor cells. We also established mouse ESC lines at both physiological glucose level (PG-mESC) and conventional hyperglycemia glucose level (HG-mESC). Concordantly, DNA methylome analysis revealed the enrichment of hypermethylated genes related to cell differentiation in HG-mESC, including Nkx6−1. Our results suggested that hyperglycemia dysregulated the epigenome at early fetal development, possibly leading to impaired pancreatic development.