In this paper, we evaluate the impacts of historic strong El Niño events on the coastal Mississippi-Alabama (MS-AL) hydroclimate. The normal physical association is that the increase in soil moisture, as a result of greater precipitation, is also associated with increased streamflow. When compared to the historic (1960–2015) long-term average, January through August streamflow volumes for five unimpaired streamflow gages located in coastal MS-AL exhibit an average increase of ~20% following a strong El Niño event. This overall increase was due to above-average precipitation during the winter-spring (January through April) season, with the corresponding average increase in streamflow volume for the five gages ~32%. In evaluating the temporal (monthly) variability of streamflow, we observe that the summer (June through August) season was dry following strong El Niño events, with streamflow volumes for the five gages decreasing by an average of ~21%. The agricultural industry in coastal MS-AL produces a variety of crops including cotton and peanuts. The typical planting season for these crops ends in mid-June with harvesting occurring in early September. Thus, the primary growing season for these crops is June–August. Given the lack of impoundments and irrigated lands in coastal MS-AL, the agricultural sector would be severely impacted by an El Niño driven drier summer. When evaluating the influence of the 2015–2016 El Niño on January through August 2016 streamflow, a similar pattern was observed in which high winter–spring streamflow was followed by diminished summer streamflow. Full article

The electrical and optical properties of semiconducting transition metal dichalcogenides (TMDs) can be tuned by controlling their composition and the number of layers they have. Among various TMDs, the monolayer WSe₂ has a direct bandgap of 1.65 eV and exhibits p-type or bipolar behavior, depending on the type of contact metal. Despite these promising properties, a lack of efficient large-area production methods for high-quality, uniform WSe₂ hinders its practical device applications. Various methods have been investigated for the synthesis of large-area monolayer WSe₂, but the difficulty of precisely controlling solid-state TMD precursors (WO₃, MoO₃, Se, and S powders) is a major obstacle to the synthesis of uniform TMD layers. In this work, we outline our success in growing large-area, high-quality, monolayered WSe₂ by utilizing methane (CH₄) gas with precisely controlled pressure as a promoter. When compared to the catalytic growth of monolayered WSe₂ without a gas-phase promoter, the catalytic growth of the monolayered WSe₂ with a CH₄ promoter reduced the nucleation density to 1/1000 and increased the grain size of monolayer WSe₂ up to 100 μm. The significant improvement in the optical properties of the resulting WSe₂ indicates that CH₄ is a suitable candidate as a promoter for the synthesis of TMD materials, because it allows accurate gas control. Full article

MicroRNAs (miRNAs) are endogenous non-coding small RNAs that downregulate target gene expression by imperfect base-pairing with the 3′ untranslated regions (3′UTRs) of target gene mRNAs. MiRNAs play important roles in regulating cancer cell proliferation, stemness maintenance, tumorigenesis, cancer metastasis, and cancer therapeutic resistance. While studies have shown that dysregulation of miRNA-205-5p (miR-205) expression is controversial in different types of human cancers, it is generally observed that miR-205-5p expression level is downregulated in breast cancer and that miR-205-5p exhibits a tumor suppressive function in breast cancer. This review focuses on the role of miR-205-5p dysregulation in different subtypes of breast cancer, with discussions on the effects of miR-205-5p on breast cancer cell proliferation, epithelial–mesenchymal transition (EMT), metastasis, stemness and therapy-resistance, as well as genetic and epigenetic mechanisms that regulate miR-205-5p expression in breast cancer. In addition, the potential diagnostic and therapeutic value of miR-205-5p in breast cancer is also discussed. A comprehensive list of validated miR-205-5p direct targets is presented. It is concluded that miR-205-5p is an important tumor suppressive miRNA capable of inhibiting the growth and metastasis of human breast cancer, especially triple negative breast cancer. MiR-205-5p might be both a potential diagnostic biomarker and a therapeutic target for metastatic breast cancer. Full article

The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has shown strong and explicit cancer cell-selectivity, which results in little toxicity toward normal tissues, and has been recognized as a potential, relatively safe anticancer agent. However, several cancers are resistant to the apoptosis induced by TRAIL. A recent study found that shikonin b (alkannin, 5,8-dihydroxy-2-[(1S)-1-hydroxy-4-methylpent-3-en-1-yl]naphthalene-1,4-dione) might induce apoptosis in TRAIL-resistant cholangiocarcinoma cells through reactive oxygen species (ROS)-mediated caspases activation. However, the strong cytotoxic activity has limited its potential as an anticancer drug. Thus, the current study intends to discover novel shikonin derivatives which can sensitize the liver cancer cell to TRAIL-induced apoptosis while exhibiting little toxicity toward the normal hepatic cell. The trypan blue exclusion assay, western blot assay, 4′,6-diamidino-2-phenylindole (DAPI) staining and the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay as well as the ‘comet’ assay, were used to study the underlying mechanisms of cell death and to search for any mechanisms of an enhancement of TRAIL-mediated apoptosis in the presence of ASH. Herein, we demonstrated that non-cytotoxic doses of acetylshikonin (ASH), one of the shikonin derivatives, in combination with TRAIL, could promote apoptosis in HepG2 cells. Further studies showed that application of ASH in a non-cytotoxic dose (2.5 μM) could increase intracellular ROS production and induce DNA damage, which might trigger a cell intrinsic apoptosis pathway in the TRAIL-resistant HepG2 cell. Combination treatment with a non-cytotoxic dose of ASH and TRAIL activated caspase and increased the cleavage of PARP-1 in the HepG2 cell. However, when intracellular ROS production was suppressed by N-acetyl-l-cysteine (NAC), the synergistic effects of ASH and TRAIL on hepatocellular carcinoma (HCC) cell apoptosis was abolished. Furthermore, NAC could alleviate p53 and the p53 upregulated modulator of apoptosis (PUMA) expression induced by TRAIL and ASH. Small (or short) interfering RNA (siRNA) targeting PUMA or p53 significantly reversed ASH-mediated sensitization to TRAIL-induced apoptosis. In addition, Bax gene deficiency also abolished ASH-induced TRAIL sensitization. An orthotopical HCC implantation mice model further confirmed that co-treated ASH overcomes TRAIL resistance in HCC cells without exhibiting potent toxicity in vivo. In conclusion, the above data suggested that ROS could induce DNA damage and activating p53/PUMA/Bax signaling, and thus, this resulted in the permeabilization of mitochondrial outer membrane and activating caspases as well as sensitizing the HCC cell to apoptosis induced by TRAIL and ASH treatment. Full article

The title compound 1-octyl-3-(3-(1-methylpyrrolidiniumyl)propyl)imidazolium bis(trifluoromethane)sulfonimide was prepared in three steps. This asymmetrical dicationic ionic liquid (ADIL) is composed of two different positively charged head groups (1-octylimidazolium and methylpyrrolidinium cations), which are linked through a propyl alkyl chain and by two bis(trifluoromethane)sulfonimide anions. The final ADIL was obtained by a simple metathesis reaction of the corresponding dibromide ionic liquid, in turn prepared by alkylation of 3-(3-bromopropyl)-1-propylimidazolium bromide. The ADIL structure and those of its precursors were confirmed through NMR and infrared spectroscopy, and the thermal properties of all compounds were evaluated by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). Density, solubility, and viscosity were measured for the prepared compounds. Full article

We introduce a class consisting of what we call quasi-periodic limit functions and then establish the relation between quasi-periodic limit functions and asymptotically quasi-periodic functions. At last, these quasi-periodic limit functions are applied to study the existence of asymptotically quasi-periodic solutions of abstract Cauchy problems. Full article

Cancer cells rely on aberrant transcription for growth and survival. Cyclin-dependent kinases (CDKs) play critical roles in regulating gene transcription by modulating the activity of RNA polymerase II (RNAPII). THZ1, a selective covalent inhibitor of CDK7, has antitumor effects in several human cancers. In this study, we investigated the role and therapeutic potential of CDK7 in regulating the angiogenic activity of endothelial cells and human renal cell carcinoma (RCC). Our results revealed that vascular endothelial growth factor (VEGF), a critical activator of angiogenesis, upregulated the expression of CDK7 and RNAPII, and the phosphorylation of RNAPII at serine 5 and 7 in human umbilical vein endothelial cells (HUVECs), indicating the transcriptional activity of CDK7 may be involved in VEGF-activated angiogenic activity of endothelium. Furthermore, through suppressing CDK7 activity, THZ1 suppressed VEGF-activated proliferation and migration, as well as enhanced apoptosis of HUVECs. Moreover, THZ1 inhibited VEGF-activated capillary tube formation and CDK7 knockdown consistently diminished tube formation in HUVECs. Additionally, THZ1 reduced VEGF expression in human RCC cells (786-O and Caki-2), and THZ1 treatment inhibited tumor growth, vascularity, and angiogenic marker (CD31) expression in RCC xenografts. Our results demonstrated that CDK7-mediated transcription was involved in the angiogenic activity of endothelium and human RCC. THZ1 suppressed VEGF-mediated VEGFR2 downstream activation of angiogenesis, providing a new perspective for antitumor therapy in RCC patients. Full article

A number of new symmetrically and asymmetrically 2,3-disubstituted quinoxalines were synthesized through functionalization of 2,3-dichloroquinoxaline (2,3-DCQ) with a variety of sulfur and/or nitrogen nucleophiles. The structures of the obtained compounds were established based on their spectral data and elemental analysis. The antimicrobial activity for the prepared compounds was investigated against four bacterial species and two fungal strains. The symmetrically disubstituted quinoxalines 2, 3, 4, and 5 displayed the most significant antibacterial activity, while compounds 6a, 6b, and the pentacyclic compound 10 showed considerable antifungal activity. Furthermore, compounds 3f, 6b showed broad antimicrobial spectrum against most of the tested strains. Full article

The dorsal striatum is important for the development of drug addiction; however, the role of dopamine D1 receptor (D1R) expressing medium-sized spiny striatonigral (direct pathway) neurons (D1-MSNs) in regulating excessive methamphetamine intake remains elusive. Here we seek to determine if modulating D1-MSNs in the dorsal striatum alters methamphetamine self-administration in animals that have demonstrated escalation of self-administration. A viral vector-mediated approach was used to induce expression of the inhibitory (G_i coupled-hM₄D) or stimulatory (G_s coupled-rM₃D) designer receptors exclusively activated by designer drugs (DREADDs) engineered to specifically respond to the exogenous ligand clozapine-N-oxide (CNO) selectively in D1-MSNs in the dorsal striatum. CNO in animals expressing hM₄D increased responding for methamphetamine compared to vehicle in a within subject treatment paradigm. CNO in animals that did not express DREADDs (DREADD naïve-CNO) or expressed rM₃D did not alter responding for methamphetamine, demonstrating specificity for hM₄D-CNO interaction in increasing self-administration. Postmortem tissue analysis reveals that hM₄D-CNO animals had reduced Fos immunoreactivity in the dorsal striatum compared to rM₃D-CNO animals and DREADD naïve-CNO animals. Cellular mechanisms in the dorsal striatum in hM₄D-CNO animals reveal enhanced expression of D1R and Ca²⁺/calmodulin-dependent kinase II (CaMKII). Conversely, rM₃D-CNO animals had enhanced activity of extracellular signal-regulated kinase (Erk1/2) and Akt in the dorsal striatum, supporting rM₃D-CNO interaction in these animals compared with drug naïve controls, DREADD naïve-CNO and hM₄D-CNO animals. Our studies indicate that transient inhibition of D1-MSNs-mediated strengthening of methamphetamine addiction-like behavior is associated with cellular adaptations that support dysfunctional dopamine signaling in the dorsal striatum. Full article

Redox imbalance is an adverse on-going phenomenon in renal transplant recipients (RTR). Vitamin E has important antioxidant properties that counterbalance its deleterious effects. However, plasma vitamin E affinity with lipids challenges interpretation of its levels. To test the hypothesis that erythrocyte membranes represent a lipids-independent specimen to estimate vitamin E status, we performed a cross-sectional study in a cohort of adult RTR (n = 113) recruited in a university setting (2015–2018). We compared crude and total lipids-standardized linear regression-derived coefficients of plasma and erythrocyte tocopherol species in relation to clinical and laboratory parameters. Strongly positive associations of fasting lipids with plasma tocopherol became inverse, rather than absent, in total lipids-standardized analyses, indicating potential overadjustment. Whilst, no variables from the lipids domain were associated with the tocopherol species measured from erythrocyte specimens. In relation to inflammatory status and clinical parameters with antioxidant activity, we found associations in directions that are consistent with either beneficial or adverse effects concerning α- or γ-tocopherol, respectively. In conclusion, erythrocytes offer a lipids-independent alternative to estimate vitamin E status and investigate its relationship with parameters over other biological domains. In RTR, α- and γ-tocopherol may serve as biomarkers of relatively lower or higher vulnerability to oxidative stress and inflammation, noticeably in opposite directions. Full article

Previous studies have suggested that in the first decade of this century the incidence of gestational diabetes (GDM) in pregnancy rose worldwide. In the Cambridge Baby Growth Study cohort we observed that this temporal trend was associated with an index of multiple deprivation and reductions in indices of insulin secretion. Deprivation level was not directly associated with GDM, suggesting that the temporal trend may relate more to other factors linked to it, such as dietary composition. In this study we investigated temporal trends in perceived food intake frequencies, derived from a qualitative, short questionnaire, in 865 pregnant Cambridge Baby Growth Study (CBGS) recruits. A number of food frequency ranks showed both temporal trends and associations with GDM, but of note is the frequency of egg consumption (negative temporal trend p = 0.03, slope = −6.2 ranks/year; negative association with GDM p = 3.0 × 10⁻⁸, slope = −0.002 increased risk/rank) as it was also positively associated with the insulin disposition index (p = 1.17 × 10⁻³, slope = 0.42 ranks. L/mmoL). These results are consistent with a potential protective effect of factors related to the frequency of egg consumption in pregnancy. Such factors may have contributed to the observed temporal trend in GDM risk but the overall detectable effect appears to have been small. Full article

Ninety German cities exceeded the European threshold on NO₂ in 2016, 65 of those cities developed countermeasures and strategies that were published in Green City Plans (GCP). In the scope of this study, 55 publicly available GCPs were evaluated in order to assess their potential for traffic turnaround at a municipal level. All GCPs were analyzed to determine in which of the mentioned five to seven fields of action the respective city had planned measures and which fields of action were prioritized. A more in-depth qualitative analysis of the main topics: Electric mobility, public transport, and mobility concepts was carried out. To get a better understanding of the potential impact of the measures elaborated in the GCPs, complementary information on municipal fleet vehicle stocks, requirements of charging infrastructure for public buses and results of the European roadmap on mobility concepts are given. The evaluation of the GCPs showed that to this day, city administrations mainly optimize the current system by measures of electrification and digitization. Electrification of municipal fleets, car-sharing fleets, and public transport buses is in the focus of the strategies. Instruments to increase non-motorised transport, sustainable commercial transport, and/or mobility concepts are mentioned, but play a minor role. However, there still has been no system change in Germany. Therefore, a substantial turnaround of the transport system (“Verkehrswende”) is necessary. This applies to integrated urban and transport planning, flexible, strong, fast PT, non-motorised and flexible operating systems. Full article

Ruminant fats are characterized by different levels of conjugated linoleic acid (CLA) and α-linolenic acid (18:3n-3, ALA), according to animal diet. Tissue fatty acids and their N-acylethanolamides were analyzed in male obese Zucker rats fed diets containing lamb meat fat with different fatty acid profiles: (A) enriched in CLA; (B) enriched in ALA and low in CLA; (C) low in ALA and CLA; and one containing a mixture of olive and corn oils: (D) high in linoleic acid (18:2n-6, LA) and ALA, in order to evaluate early lipid metabolism markers. No changes in body and liver weights were observed. CLA and ALA were incorporated into most tissues, mirroring the dietary content; eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) increased according to dietary ALA, which was strongly influenced by CLA. The n-3 highly-unsaturated fatty acid (HUFA) score, biomarker of the n-3/n-6 fatty acid ratio, was increased in tissues of rats fed animal fats high in CLA and/or ALA compared to those fed vegetable fat. DHA and CLA were associated with a significant increase in oleoylethanolamide and decrease in anandamide in subcutaneous fat. The results showed that meat fat nutritional values are strongly influenced by their CLA and ALA contents, modulating the tissue n-3 HUFA score. Full article