Search Results (41)

Climate change and anthropogenic impacts drastically affect the biogeochemical regime of the Black Sea, which contains the largest volume of sulphidic water in the world. The Sea’s oxygen inventory depends on vertical mixing that transports dissolved oxygen (DO) from the upper euphotic layer to deeper layers and on dissolved oxygen consumption for the oxidation of organic matter (OM) and reduced species of S, Fe, and Mn. Here we use a vertical one-dimensional transport model, 2DBP, forced by Copernicus data, that was coupled with the FABM-family N-P-Si-C-O-S-Mn-Fe Bottom RedOx Model BROM. The research objective of this study was to analyze the oxygen budget in the upper 350 m of the Sea and demonstrate the role of the parameterization of the acceleration of the sinking of particles covered by precipitated Mn(IV). The analysis of the oxygen budget revealed distinct patterns in oxygen consumption within different depths. In the oxic zone, the primary sink for DO is the mineralization of organic matter, whereas in the suboxic zone, dissolved Mn(II) oxidation becomes the predominant sink. The produced Mn(IV) sinks down and reacts with hydrogen sulphide several meters below, making possible the existence of the suboxic layer without detectable concentrations of DO and H₂S. Full article

Background and Objectives: Fertility tracking apps and devices are now currently available, but urinary hormone levels lack accuracy and sensitivity in timing the start of the 6-day fertile window and the precise 24 h interval of transition from ovulation to the luteal phase. We hypothesized the serum hormones estradiol (E2) and progesterone (P) might be better biomarkers for these major ovulatory cycle events, using appropriate mathematical tools. Materials and Methods: Four women provided daily blood samples for serum E2, P, and LH (luteinizing hormone) levels throughout their entire ovulatory cycles, which were indexed to the first day of dominant follicle (DF) collapse (defined as Day 0) determined by transvaginal sonography; therefore, ovulation occurred in the 24 h interval of Day −1 (last day of maximum diameter DF) to Day 0. For comparison, a Mira^TM fertility monitor was used to measure daily morning urinary LH (ULH), estrone-3-glucuronide (E3G), and pregnanediol-3-glucuronide (PDG) levels in three of these cycles. Results: There were more fluctuations in the Mira^TM hormone levels compared to the serum levels. Previously described methods, the Fertility Indicator Equation (FIE) and Area Under the Curve (AUC) algorithm, were tested for identifying the start of the fertile window and the ovulation/luteal transition point using the day-specific hormone levels. The FIE with E2 levels predicted the start of the 6-day fertile window on Day −7 (two cycles) and Day −5 (two cycles), whereas no identifying signal was found with E3G. However, both pairs of (E2, P) and (E3G, PDG) levels with the AUC algorithm signaled the Day −1 to Day 0 ovulation/luteal transition interval in all cycles. Conclusions: serum E2 and (E2, P) were better biomarkers for signaling the start of the 6-day fertile window, but both Mira^TM and serum hormone levels were successful in timing the [Day −1, Day 0] ovulatory/luteal transition interval. These results can presently be applied to urinary hormone monitors for fertility tracking and have implications for the direction of future fertility tracking technology. Full article

This paper focuses on the influence of the fractional-order (FO) resonant capacitor on the zero-voltage-switching quasi-resonant converter (ZVS QRC). The FO impedance model of the capacitor is introduced to the circuit model of the ZVS QRC; hence, a piecewise smooth FO model is developed for the converter. Numerical solutions of the converter are obtained by using both the fractional Adams–Bashforth–Moulton (F-ABM) method and Oustaloup’s rational approximation method. In addition, the analytical solution of the converter is obtained by the Grünwald–Letnikov (GL) definition, which reveals the influence of the FO resonant capacitor on the zero-crossing point (ZCP) and resonant state of the converter. An experimental platform was built to verify the results of the theoretical analysis and numerical calculation. Full article

We review the importance of monocytic differentiation and differentiation induction in non-APL (acute promyelocytic leukemia) variants of acute myeloid leukemia (AML), a malignancy characterized by proliferation of immature myeloid cells. Even though the cellular differentiation block is a fundamental characteristic, the AML cells can show limited signs of differentiation. According to the French–American–British (FAB-M4/M5 subset) and the World Health Organization (WHO) 2016 classifications, monocytic differentiation is characterized by morphological signs and the expression of specific molecular markers involved in cellular communication and adhesion. Furthermore, monocytic FAB-M4/M5 patients are heterogeneous with regards to cytogenetic and molecular genetic abnormalities, and monocytic differentiation does not have any major prognostic impact for these patients when receiving conventional intensive cytotoxic therapy. In contrast, FAB-M4/M5 patients have decreased susceptibility to the Bcl-2 inhibitor venetoclax, and this seems to be due to common molecular characteristics involving mitochondrial regulation of the cellular metabolism and survival, including decreased dependency on Bcl-2 compared to other AML patients. Thus, the susceptibility to Bcl-2 inhibition does not only depend on general resistance/susceptibility mechanisms known from conventional AML therapy but also specific mechanisms involving the molecular target itself or the molecular context of the target. AML cell differentiation status is also associated with susceptibility to other targeted therapies (e.g., CDK2/4/6 and bromodomain inhibition), and differentiation induction seems to be a part of the antileukemic effect for several targeted anti-AML therapies. Differentiation-associated molecular mechanisms may thus become important in the future implementation of targeted therapies in human AML. Full article

(1) Background: FABMs (fertility awareness-based methods) are methods that rely on the observation of clinical signs related to fertility found in women, the so-called fertility bioindicators. They can be a valuable tool for diagnosing monthly cycle disorders and infertility, for example, among patients with PCOS (polycystic ovary syndrome). Until now, it has been difficult for women with PCOS to use FABM, due to the difficulty of describing fertility bioindicators and their disorders due to the biology of the syndrome. The new InVivo sympto-thermal method with standardized cervical mucus assessment may provide a valuable diagnostic and therapeutic tool for observing the monthly cycle in this group of women. (2) Methods: The monthly cycle was evaluated in a group of 32 women of reproductive age. A total of 108 monthly cycle observation cards were analyzed: 35 monthly cycle cards were collected from 18 women with PCOS, and 73 monthly cycle cards collected from 14 healthy women. In addition, 32 pairs of macroscopic and microscopic images were evaluated: 17 pairs from the study group (four subjects) and 15 pairs from women in the control group (six subjects). (3) Results: We showed that in the group of patients with PCOS, menstruation was longer (p = 0.000814), the number of mucus peaks was statistically higher (p = 0.040747), and the interquartile range (IQR) of the duration of the follicular phase (calculated according to the BBT) was significantly higher (8 days) compared to women in the control group. We also observed that among all the women studied, the microscopic image of cervical mucus correlated with the cycle phase described in the observation card, as determined by reference to the BBT chart, provided that it showed the correct features. (4) Conclusions: Systematic maintenance of monthly cycle observation charts using the InVivo method can be an important supplement to the medical history, as it allows for a thorough assessment of, among others, the timing of monthly bleeding, cervical mucus symptoms, BBT changes, and the duration of the follicular and luteal phases among both healthy and PCOS women. Full article

Even though morphological signs of differentiation have a minimal impact on survival after intensive cytotoxic therapy for acute myeloid leukemia (AML), monocytic AML cell differentiation (i.e., classified as French/American/British (FAB) subtypes M4/M5) is associated with a different responsiveness both to Bcl-2 inhibition (decreased responsiveness) and possibly also bromodomain inhibition (increased responsiveness). FAB-M4/M5 patients are heterogeneous with regard to genetic abnormalities, even though monocytic differentiation is common for patients with Nucleophosmin 1 (NPM1) insertions/mutations; to further study the heterogeneity of FAB-M4/M5 patients we did a proteomic and phosphoproteomic comparison of FAB-M4/M5 patients with (n = 13) and without (n = 12) NPM1 mutations. The proteomic profile of NPM1-mutated FAB-M4/M5 patients was characterized by increased levels of proteins involved in the regulation of endocytosis/vesicle trafficking/organellar communication. In contrast, AML cells without NPM1 mutations were characterized by increased levels of several proteins involved in the regulation of cytoplasmic translation, including a large number of ribosomal proteins. The phosphoproteomic differences between the two groups were less extensive but reflected similar differences. To conclude, even though FAB classification/monocytic differentiation are associated with differences in responsiveness to new targeted therapies (e.g., Bcl-2 inhibition), our results shows that FAB-M4/M5 patients are heterogeneous with regard to important biological characteristics of the leukemic cells. Full article

AML is a highly aggressive and heterogeneous form of hematological cancer. Proteomics-based stratification of patients into more refined subgroups may contribute to a more precise characterization of the patient-derived AML cells. Here, we reanalyzed liquid chromatography-tandem mass spectrometry (LC-MS/MS) generated proteomic and phosphoproteomic data from 26 FAB-M4/M5 patients. The patients achieved complete hematological remission after induction therapy. Twelve of them later developed chemoresistant relapse (RELAPSE), and 14 patients were relapse-free (REL_FREE) long-term survivors. We considered not only the RELAPSE and REL_FREE characteristics but also integrated the French-American-British (FAB) classification, along with considering the presence of nucleophosmin 1 (NPM1) mutation and cytogenetically normal AML. We found a significant number of differentially enriched proteins (911) and phosphoproteins (257) between the various FAB subtypes in RELAPSE patients. Patients with the myeloblastic M1/M2 subtype showed higher levels of RNA processing-related routes and lower levels of signaling related to terms like translation and degranulation when compared with the M4/M5 subtype. Moreover, we found that a high abundance of proteins associated with mitochondrial translation and oxidative phosphorylation, particularly observed in the RELAPSE M4/M5 NPM1 mutated subgroup, distinguishes relapsing from non-relapsing AML patient cells with the FAB subtype M4/M5. Thus, the discovery of subtype-specific biomarkers through proteomic profiling may complement the existing classification system for AML and potentially aid in selecting personalized treatment strategies for individual patients. Full article

Due to their long half-life, polychlorinated biphenyls (PCBs) tend to contaminate not only coastal areas, but they travel over long distances, eventually reaching remote areas such the Arctic. The physical and biogeochemical features of every coastal area govern the main distribution patterns of freshly introduced PCBs into the marine system. Some of these processes are determined by chemical properties of the individual PCB congener. Thus, atmospheric influx along with ad/absorption on non-living organic material, photolytical and biological degradation processes vary from one PCB congener to another. For a detailed fate analysis of individual congeners, we developed a new chemical model, based on the GOTM-ECOSMO-FABM model framework. Here, we exemplarily present results for PCB₁₅₃ based on 1D simulations of four regions in the North-Baltic Sea. The study area is characterized by different hydrodynamic and biogeochemical conditions. We investigate the impact of resuspension, mixing and the biological pump, sea ice and tides on the final phasal distribution of PCB₁₅₃. Different combinations of these factors lead to the development of different areas of PCB₁₅₃ accumulation, with the formation of hotspot areas, and influence the total uptake and concentration of PCB₁₅₃ in the water column. As a result, two major dynamics determine the fate of PCB₁₅₃ in the coastal ocean: (i) Primary production leads to PCB₁₅₃ being adsorbed by organic material. Partitioning to organic material and sedimentation of organic particles removes dissolved PCB₁₅₃ from the surface ocean and increases atmospheric influx. (ii) Tidal-induced resuspension and mixing control the benthic–pelagic exchange of PCB₁₅₃ and its distribution in the water column. Depending on the resuspension regime and stratification, sediments can become a permanent (Gotland Deep, the Baltic Sea) or seasonal sink for PCB₁₅₃. In regions with seasonal stratification and high near bottom turbulence (Northern North Sea), resuspension events can lead to pronounced peaks in PCB₁₅₃ concentrations and can therefore have a major impact on bioaccumulation. Under the conditions of permanent mixing and high bottom turbulence (Southern North Sea, Bothnian Bay), pollutants are hardly accumulating in sediments. Full article

Stereocalpin B, a new cyclic depsipeptide (1), and a new dibenzofuran derivative (3), were isolated from the Antarctic lichen, Ramalina terebrata (Ramalinaceae), along with a known cyclic depsipeptide (2). The structures of new compounds were characterized by comprehensive spectrometric analyses; high-resolution fast atom bombardment mass spectrometry (HR-FABMS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Stereocalpin B (1) existed in a rotameric equilibrium, which was confirmed using nuclear Overhauser effect spectroscopy (NOESY)/exchange spectroscopy (EXSY) spectrum. Absolute configurations of the amino acid units in 1 were assigned using the advanced Marfey’s method and subsequent NOESY analysis of the 5-hydroxy-2,4-dimethyl-3-oxo-decanoic acid residue confirmed the complete stereochemistry of 1. Compounds 1-3 exhibited moderate antimicrobial activities against E. coli, with the IC₅₀ values ranging from 18–30 μg/mL. Compound 2 exhibited cell growth inhibition against HCT116 cell lines, with the IC₅₀ value of 20 ± 1.20 μM, and compounds 1 and 2 also showed potent anti-inflammatory activities against lipopolysaccharide (LPS)-induced RAW264.7 macrophages with the IC₅₀ values ranging from 5–7 μM. Full article

Gold(I) complexes with phosphine ligands—[Au(TrippyPhos)Cl] (1) (TrippyPhos = 1-[2-[bis(tert-butyl)phosphino]phenyl]-3,5-diphenyl-1H-pyrazole), [Au(BippyPhos)Cl]0.5CH₂Cl₂ (2) (BippyPhos = 5-(di-tert-butylphosphino)-1${}^{\prime }$, 3${}^{\prime }$, 5${}^{\prime }$-triphenyl-1${}^{\prime }$H-[1,4${}^{\prime }$]bipyrazole), and [Au(meCgPPh)Cl] (3) (meCgPPh = 1,3,5,7-tetramethyl-6-phenyl-2,4,8-trioxa-6-phosphaadamantane—were investigated as types of bioactive gold metallodrugs. Complexes (1)–(3) were characterized using IR, ¹H, ¹³C, ³¹P NMR spectroscopy, elemental analysis and mass spectrometry (FAB-MS). Complexes of (1) and (2) exhibited substantial in vitro cytotoxicity (IC₅₀ = 0.5–7.0 $\mathsf{\mu }$M) against both the cisplatin-sensitive and -resistant variants of the A2780 human ovarian carcinoma cell line, as well as against the A549 human lung carcinoma, K562 chronic myelogenous leukemia, and HeLa (human cervix carcinoma) cells. However, among the compounds studied, complex (2) showed the most promising biological properties: the highest stability in biologically relevant media, selectivity towards cancer cells over the non-cancer cells (HUVEC, human umbilical vein endothelial cells), and the highest inhibitory effect on cytosolic NADPH-dependent reductases in A2780 and A2780cis cells among the gold complexes under analysis. Full article

The fate of microplastics (MP) in seawater is heavily influenced by the biota: the density of MP particles can be changed due to biofouling, which affects sinking, or MP can be digested by zooplankton and transferred into fecal pellets with increased sinking rate. We hypothesize that seasonal production and degradation of organic matter, and corresponding changes in the plankton ecosystem affect the MP capacity for transportation and burying in sediments in different seasons. This is simulated with a coupled hydrodynamical-biogeochemical model that provides a baseline scenario of the seasonal changes in the planktonic ecosystem and changes in the availability of particulate and dissolved organic matter. In this work, we use a biogeochemical model OxyDep that simulates seasonal changes of phytoplankton (PHY), zooplankton (HET), dissolved organic matter (DOM) and detritus (POM). A specifically designed MP module considers MP particles as free particles ($M{P}_{free}$), particles with biofouling ($M{P}_{biof}$), particles consumed by zooplankton ($M{P}_{het}$) and particles in detritus, including fecal pellets ($M{P}_{det}).$ A 2D coupled benthic-pelagic vertical transport model 2DBP was applied to study the effect of seasonality on lateral transport of MP and its burying in the sediments. OxyDep and MP modules were coupled with 2DBP using Framework for Aquatic Biogeochemical Modelling (FABM). A depletion of MP from the surface water and acceleration of MP burying in summer period compared to the winter was simulated numerically. The calculations confirm the observations that the “biological pump” can be one of the important drivers controlling the quantity and the distribution of MP in the water column. Full article

The reaction of bidentate N-S-thione-Schiff base, (E)-benzyl 2-(1-(4-chlorophenyl)-ethylidene)hydrazinecarbodithioate, with Cu(NO₃)₂·3H₂O produced a cis-Cu(II) complex. The molecular structure was confirmed and characterized by CHN-EA, FAB-MS, IR, and UV-Vis analyses. The XRD supported cis-isomer of the bis anionic bidentate N (azomethine) and S (thiol) ligand coordination mode in tetrahedrally distorted square planar, rarely reported in the literature. The results of the XRD-bond lengths were in perfect agreement with the density functional theory (DFT) calculation. DFT-calculated angles around the Cu(II) center displayed slightly less distortion around the metal center from those of XRD. Additionally, the thermal stability of the complex was evaluated via thermal gravimetric analysis (TGA). Two-dimensional fingerprint (2D-FP), Hirshfeld surface analysis (HSA), and molecular electrostatic potential (MEP) support the XRD-packing results with the existence of the H⸱⸱⸱Cl and CH⸱⸱⸱π bonds as the main interactions in the crystal lattice of the desired complex. Full article

Cervical cancer is among the leading causes of death in women. Chemotherapy options available for cervical cancer include highly cytotoxic drugs such as taxol, cisplatin, 5-florouracil, and doxorubicin, which are not specific. In the current study, we have identified a new peptide conjugate (Fur⁴-2-Nal³-Ala²-Phe¹-CONH₂) (conjugate 4), from screening of a small library of tripeptide-conjugates of furan, as highly potent anticancer compound against human cervical cancer cells (HeLa cells) (IC₅₀ = 0.15 ± 0.05 µg/mL or 0.28 +/− 0.09 µM). Peptides were constructed on Rink amide resin from C- to N-terminus followed by capping by α-furoic acid moiety. The synthesized peptides were purified by recycling RP-HPLC, and structures of all the peptides were confirmed by using FABMS/ESIMS, ¹H- NMR, ¹³C-NMR, and HR-FABMS. Conjugate 4 was furthermore found to be specifically active against human cervical cancer cells since it did not inhibit the proliferation of other human normal cells (HUVEC (human umbilical vein endothelial cells) and IMR-90 (normal human fibroblasts)), and cancer cells tested (HUVEC, MCF-7, and MDA-MB-231 cells), as well as in mice 3T3 cells (normal fibroblasts). This study revealed a good structure activity relationship of various peptide conjugates. Conjugate 4 in branched forms (4a and 4b) were also synthesized and evaluated against HeLa cells, and results revealed that both were inactive. Atomic force microscopy (AFM) studies and staining with rhodamine 123 and propidium iodide (PI) revealed that conjugate 4 possesses a membranolytic effect and causes the loss of mitochondrial membrane potential. Full article

Climate extremes, which are steadily increasing in frequency, can have detrimental consequences for lake ecosystems. We used a state-of-the-art, one-dimensional, hydrodynamic-ecosystem model [General Ocean Turbulence Model (GOTM)-framework for aquatic biogeochemical models (FABM)-PCLake] to determine the influence of extreme climate events on a temperate and temporarily summer stratified lake (Lake Bryrup, Denmark). The model was calibrated (eight years data) and validated (two years data), and the modeled variables generally showed good agreement with observations. Then, a span of extreme warming scenarios was designed based on weather data from the heatwave seen over northern Europe in May–July 2018, mimicking situations of extreme warming returning every year, every three years, and every five years in summer and all year round, respectively. We found only modest impacts of the extreme climate events on nutrient levels, which in some scenarios decreased slightly when looking at the annual mean. The most significant impacts were found for phytoplankton, where summer average chlorophyll a concentrations and cyanobacteria biomass peaks were up to 39% and 58% higher than during baseline, respectively. As a result, the phytoplankton to nutrient ratios increased during the heat wave experiments, reflecting an increased productivity and an increased cycling of nutrients in the pelagic. The phytoplankton blooms occurred up to 15 days earlier and lasted for up to half a month longer during heat wave years relative to the baseline. Our extreme scenarios illustrated and quantified the large impacts of a past heat wave (observed 2018) and may be indicative of the future for many temperate lakes. Full article

Chemical investigation of Cordia millenii, Baker resulted in the isolation of a new depsidone, cordidepsine (1), along with twelve known compounds including cyclooctasulfur (2), lup-20(29)-en-3-triacontanoate (3), 1-(26-hydroxyhexacosanoyl)glycerol (4), glyceryl-1-hexacosanoate (5) betulinic acid (6), lupenone (7), β-amyrone (8), lupeol (9), β-amyrin (10), allantoin (11), 2′-(4-hydroxyphenyl)ethylpropanoate (12) and stigmasterol glycoside (13). Hemi-synthetic reactions were carried out on two isolated compounds (5 and 6) to afford two new derivatives, that is, cordicerol A (14) and cordicerol B (15), respectively. The chemical structures of all the compounds were established based on analysis and interpretation of spectroscopic data such as electron ionization mass spectrometry (EI–MS), high resolution electrospray ionization mass spectrometry (HR-ESI–MS), fast atom bombardment mass spectrometry (FAB–MS), one dimension and two dimension nuclear magnetic resonance (1D and 2D-NMR) spectral data as well as X-ray crystallography (XRC). Lupeol ester derivatives [Lup-20(29)-en-3-triacontanoate (3)], monoglycerol derivatives [1-(26-hydroxyhexacosanoyl)glycerol (4) and glyceryl-1 hexacosanoate (5)] were isolated for the first time from Cordia genus while sulfur allotrope [cyclooctasulfur (2)] was isolated for the first time from plant origin. Biological assays cordidepsine (1) exhibited significant anti-HIV integrase activity with IC₅₀ = 4.65 μM; EtOAc extract of stem barks, EtOAc fraction of roots and leaves were not toxic against 3T3 cells. Full article