New Ethylated Derivatives of Sulfur- and Nitrogen-Containing Artifacts from Tenodera sinensis Egg Pod and Their Anti-Renal Fibrosis.

Three pairs of enantiomers and one achiral molecule that are new ethylated derivatives of sulfur and nitrogen-containing compounds named mantidisamides E-H (1-4), along with twenty known ones (5-24), were derived from the ethanol extract of Tenodera sinensis Saussure. The structures of these new compounds and their absolute configurations were assigned on the basis of spectroscopic analyses and computational methods. The assessment of activities in NRK-52e cells induced by TGF-ß1 demonstrated that the previously undescribed compounds 1 and 2 exhibited a significant capacity to inhibit the expression of proteins (fibronectin, collagen I, and α-SMA). Moreover, the biological activity of these compounds was found to increase with rising concentrations. Notably, compounds 1-4 should be artifacts; however, undescribed compounds 1 and 2, which possessed obvious biological activity, might be attractive for chemists and biologists due to the potential for more detailed exploration of their properties. It is worth mentioning that compounds 1 and 2 remain novel structures even in the absence of the ethoxy group.

Anti-Jamming Resource-Allocation Method in the EH-CIoT Network through LWDDPG Algorithm.

In the Energy-Harvesting (EH) Cognitive Internet of Things (EH-CIoT) network, due to the broadcast nature of wireless communication, the EH-CIoT network is susceptible to jamming attacks, which leads to a serious decrease in throughput. Therefore, this paper investigates an anti-jamming resource-allocation method, aiming to maximize the Long-Term Throughput (LTT) of the EH-CIoT network. Specifically, the resource-allocation problem is modeled as a Markov Decision Process (MDP) without prior knowledge. On this basis, this paper carefully designs a two-dimensional reward function that includes throughput and energy rewards. On the one hand, the Agent Base Station (ABS) intuitively evaluates the effectiveness of its actions through throughput rewards to maximize the LTT. On the other hand, considering the EH characteristics and battery capacity limitations, this paper proposes energy rewards to guide the ABS to reasonably allocate channels for Secondary Users (SUs) with insufficient power to harvest more energy for transmission, which can indirectly improve the LTT. In the case where the activity states of Primary Users (PUs), channel information and the jamming strategies of the jammer are not available in advance, this paper proposes a Linearly Weighted Deep Deterministic Policy Gradient (LWDDPG) algorithm to maximize the LTT. The LWDDPG is extended from DDPG to adapt to the design of the two-dimensional reward function, which enables the ABS to reasonably allocate transmission channels, continuous power and work modes to the SUs, and to let the SUs not only transmit on unjammed channels, but also harvest more RF energy to supplement the battery power. Finally, the simulation results demonstrate the validity and superiority of the proposed method compared with traditional methods under multiple jamming attacks.

Modeling and Performance Analysis of LBT-Based RF-Powered NR-U Network for IoT.

Energy harvesting combined with spectrum sharing offers a promising solution to the growing demand for spectrum while keeping energy costs low. New Radio Unlicensed (NR-U) technology enables telecom operators to utilize unlicensed spectrum in addition to the licensed spectrum already in use. Along with this, the energy demands for the Internet of Things (IoT) can be met through energy harvesting. In this regard, the ubiquity and ease of implementation make the RF-powered NR-U network a sustainable solution for cellular IoT. Using a Markov chain, we model the NR-U network with nodes powered by the base station (BS). We derive closed-form expressions for the normalized saturated throughput of nodes and the BS, along with the mean packet delay at the node. Additionally, we compute the transmit outage probability of the node. These quality of service (QoS) parameters are analyzed for different values of congestion window size, TXOP parameter, maximum energy level, and energy threshold of the node. Additionally, the effect of network density on collision, transmission, and energy harvesting probabilities is observed. We validate our model through simulations.

Evidence of synergistic mechanisms of hepatoprotective botanical herbal preparation of Pueraria montana var. lobata and Schisandra sphenanthera.

Background: Pueraria montana var. lobata (Willd.) Maesen & S.M.Almeida ex Sanjappa & Predeep (syn. Pueraria lobata (Willd.) Ohwi) and Schisandra sphenanthera Rehder & E.H. Wilson are traditional edible and medicinal hepatoprotective botanical drugs. Studies have shown that the combination of two botanical drugs enhanced the effects of treating acute liver injury (ALI), but the synergistic effect and its action mechanisms remain unclear. This study aimed to investigate the synergistic effect and its mechanism of the combination of Pueraria montana var. lobata (Willd.) Maesen & S.M.Almeida ex Sanjappa & Predeep (syn. Pueraria lobata (Willd.) Ohwi) (PM) and Schisandra sphenanthera Rehder & E.H. Wilson (SS) in the treatment of ALI. Methods: High performance liquid chromatography (HPLC) were utilized to conduct the chemical interaction analysis. Then the synergistic effects of botanical hybrid preparation of PM-SS (BHP PM-SS) against ALI were comprehensively evaluated by the CCl4 induced ALI mice model. Afterwards, symptom-oriented network pharmacology, transcriptomics and metabolomics were applied to reveal the underlying mechanism of action. Finally, the key target genes were experimentally by RT-qPCR. Results: Chemical analysis and pharmacodynamic experiments revealed that BHP PM-SS was superior to the single botanical drug, especially at 2:3 ratio, with a better dissolution rate of active ingredients and synergistic anti-ALI effect. Integrated symptom-oriented network pharmacology combined with transcriptomics and metabolomics analyses showed that the active ingredients of BHP PM-SS could regulate Glutathione metabolism, Pyrimidine metabolism, Arginine biosynthesis and Amino acid sugar and nucleotide sugar metabolism, by acting on the targets of AKT1, TNF, EGFR, JUN, HSP90AA1 and STAT3, which could be responsible for the PI3K-AKT signaling pathway, MAPK signaling pathway and Pathway in cancer to against ALI. Conclusion: Our study has provided compelling evidence for the synergistic effect and its mechanism of the combination of BHP PM-SS, and has contributed to the development and utilization of BHP PM-SS dietary supplements.

Alteration of soil pH induced by submerging/drainage and application of peanut straw biochar and its impact on Cd(II) availability in an acidic soil to indica-japonica rice varieties.

The effects of soil pH variations induced by submergence/drainage and biochar application on soil cadmium (Cd) availability to different rice (Oryza sativa L.) varieties are not well understood. This study aims to investigate the possible reasons for available Cd(II) reduction in paddy soil as influenced by biochar and to determine Cd(II) absorption and translocation rates in different parts of various rice varieties. A pot experiment in a greenhouse using four japonica and four indica rice varieties was conducted in Cd(II) contaminated paddy soil with peanut straw biochar. The results indicated that the submerging led to an increase in soil pH due to the consumption of protons (H+) by the reduction reactions of iron/manganese (Fe/Mn) oxides and sulfate (SO42-) and thus the decrease in soil available Cd(II) contents. However, the drainage decreased soil pH due to the release of protons during the oxidation of Fe2+, Mn2+, and S2- and thus the increase in soil available Cd(II) contents. Application of the biochar increased soil pH during soil submerging and inhibited the decline in soil pH during soil drainage, and thus decreased soil available Cd(II) contents under both submerging and drainage conditions. The indica rice varieties absorbed more Cd(II) in their roots and accumulated higher amounts of Cd(II) in their shoots and grains than the japonica rice varieties. The Cd(II) sensitive varieties exhibited a greater absorption and translocation rate of Cd(II) compared to the tolerant varieties of both indica and japonica rice. Biochar inhibited the absorption and accumulation of Cd(II) in the rice varieties, which ultimately lowered the Cd(II) contents in rice grains below the national food safety limit (0.2 mg kg-1). Overall, planting japonica rice varieties in Cd(II) polluted paddy soils combined with the use of biochar can effectively reduce Cd(II) content in rice grains which protects human health against Cd(II) toxicity.

Synergy effect of silicate fertilizer and iron slag: A sustainable approach for mitigating methane emission in rice farming.

Although silicate fertilizer has been recently recognized for its ability to suppress methane (CH4) emissions in paddy fields, the effects of its consecutive application during the rice farming period are still a subject of debate. Moreover, while it was known that silicate fertilizer can mitigate CH4 emissions through several electron acceptors, the effect of additional application of electron acceptors have not been extensively studied. This study evaluated the effect of silicate fertilizer with varying concentrations of iron slag on CH4 emissions and rice yield over the 3 years rice farming period. Seasonal CH4 fluxes exhibited a significant decrease with the application of silicate fertilizer, with the treatment containing 2.5 % iron slag showing the maximum reduction of 35 % in 2020. Additionally, in 2021 and 2022, the application of silicate fertilizer with 2.5 % iron slag resulted in a decrease of total seasonal CH4 emission by 22 % and 23 %, respectively. Rice grain yield exhibited a significant increase with the inclusion of iron slag in the silicate fertilizer, which resulted in a 37 % and 16 % higher yield compared to no-silicate fertilization and no­iron slag silicate fertilization, respectively. Therefore, iron slag-based silicate fertilizer could be a beneficial soil amendment to mitigate CH4 emissions in rice paddy fields and improve rice productivity without negative effects on the atmospheric and soil ecosystem.

The EH domain-containing protein, EdeA, is involved in endocytosis, cell wall integrity, and pathogenicity in Aspergillus fumigatus.

Endocytosis has been extensively studied in yeasts, where it plays crucial roles in growth, signaling regulation, and cell-surface receptor internalization. However, the biological functions of endocytosis in pathogenic filamentous fungi remain largely unexplored. In this study, we aimed to functionally characterize the roles of EdeA, an ortholog of the Saccharomyces cerevisiae endocytic protein Ede1, in Aspergillus fumigatus. EdeA was observed to be distributed as patches on the plasma membrane and concentrated in the subapical collar of hyphae, a localization characteristic of endocytic proteins. Loss of edeA caused defective hyphal polarity, reduced conidial production, and fewer sites of endocytosis initiations than that of the parental wild type. Notably, the edeA null mutant exhibited increased sensitivity to cell wall-disrupting agents, indicating a role for EdeA in maintaining cell wall integrity in A. fumigatus. This observation was further supported by the evidence showing that the thickness of the cell wall in the ΔedeA mutant increased, accompanied by abnormal activation of MpkA, a key component in the cell wall integrity pathway. Additionally, the ΔedeA mutant displayed increased pathogenicity in the Galleria mellonella wax moth infection model, possibly due to alterations in cell wall morphology. Site-directed mutagenesis identified the conserved residue E348 within the third EH (Eps15 homology) domain of EdeA as crucial for its subcellular localization and functions. In conclusion, our results highlight the involvement of EdeA in endocytosis, hyphal polarity, cell wall integrity, and pathogenicity in A. fumigatus. IMPORTANCE: Aspergillus fumigatus is a significant human pathogenic fungus known to cause invasive aspergillosis, a disease with a high mortality rate. Understanding the basic principles of A. fumigatus pathogenicity is crucial for developing effective strategies against this pathogen. Previous research has underscored the importance of endocytosis in the infection capacity of pathogenic yeasts; however, its biological function in pathogenic mold remains largely unexplored. Our characterization of EdeA in A. fumigatus sheds light on the role of endocytosis in the development, stress response, and pathogenicity of pathogenic molds. These findings suggest that the components of the endocytosis process may serve as potential targets for antifungal therapy.

Effect of Halomonas titanicae on fluctuating water-line corrosion of EH40 steel.

The fluctuating water-line corrosion of EH40 steel in sterile and biotic media was investigated with a wire beam electrode. When the coupons were partially immersed in the sterile medium, the position of the low water-line acted as the cathodic zone and the area below the low water-line constantly served as the main anodic zone. The thin electrolyte layers with uneven thickness promoted the galvanic current of the region below the low water-line. Different from the sterile environment, the metabolism of Halomonas titanica with oxygen as the final electron acceptor reduced the dissolved oxygen concentration, which resulted in the position of the low water-line acting as the anodic zone.

Performance analysis of urine formed element analyzer EH-2090 was found to have good accuracy in detecting RBCs and WBCs when compared to manual microscopic.

Background: EH-2090 is Mindray's new-generation fully automatic urine formed element analyzer (hereinafter referred to as EH-2090). Currently, there are no studies on EH-2090, so we evaluated the analytical and clinical performance of this instrument to verify that it can meet daily clinical needs, and used manual microscopy as a reference method. Methods: The analytical performance of the EH-2090 was first evaluated for repeatability, linearity, reproducibility, and carryover. We collected urine samples from outpatient and inpatient departments of Peking University Shenzhen Hospital. Uncentrifuged urine was compared with the EH-2090 using the Fuchs-Rosenthal counting method-a quantitative reference method for microscopy-for comparative studies in terms of red blood cell (RBC) and white blood cell (WBC) counting accuracy. Passing-Bablok regression analysis was performed for RBC and WBC counts. Two laboratory technicians performed centrifugation and manual analysis (microscopy) to evaluate its performance at detecting RBCs, WBCs, and casts, sensitivities and specificities were calculated. Results: The EH-2090's between-run reproducibility, within-day reproducibility, between-day reproducibility, and within-laboratory reproducibility for formed components of urine all met the laboratory requirements. There was a good correlation between the counting accuracy of RBCs (r=0.965, P<0.0001) and WBCs (r=0.894, P<0.0001) by the EH-2090 and the Fuchs-Rosenthal method. The positive coincidence rates of RBC and manual microscopy were 86.08% and 92.41%, respectively, and the negative coincidence rates were 88.39% and 85.81%, respectively. The positive coincidence rates before and after the WBC review were 89.33% and 92.00%, respectively, whereas the negative ones were 77.64% and 83.23%, respectively. The positive coincidence rates before and after cast review were 77.78% and 82.05%, respectively, and the negative ones were 97.09% and 93.60%, respectively. Conclusions: The EH-2090 has good analytical and clinical performance. Its RBC and WBC counting accuracy correlates well with the quantitative reference method of microscopy.

Short- and Long-Term Storage of Non-Domesticated European Mouflon (Ovis aries musimon) Cumulus-Oocyte Complexes Recovered in Field Conditions.

Reproductive biotechnologies can be used as a supporting tool, through gamete conservation and in vitro embryo production, in the preservation of invaluable and irreplaceable animal genetic resources. In the present study, immature mouflon cumulus-oocyte complexes (COCs) collected from ovariectomized female ovaries underwent short- or long-term conservation (24 h maintained in Earle's/Hank's (EH) medium or vitrification) under field conditions and afterwards transported to the laboratory where they were cultured for in vitro maturation (IVM) and assessed for oocyte meiotic competence and bioenergetic-oxidative status. Utilization of both storage techniques led to COC morphology preservation, as well as cumulus expansion and oocyte meiotic resumption after the IVM procedure. Quantitative bioenergetic-oxidative parameters were reduced in vitrified oocytes compared with EH ones. Immature COC storage needs to be optimized in both domesticated and non-domesticated sheep as a part of the strategy to avoid the loss of valuable genotypes of these animal species.

Cancer-Related Mutations in the Sam Domains of EphA2 Receptor and Ship2 Lipid Phosphatase: A Computational Study.

The lipid phosphatase Ship2 interacts with the EphA2 receptor by forming a heterotypic Sam (sterile alpha motif)-Sam complex. Ship2 works as a negative regulator of receptor endocytosis and consequent degradation, and anti-oncogenic effects in cancer cells should be induced by hindering its association with EphA2. Herein, a computational approach is presented to investigate the relationship between Ship2-Sam/EphA2-Sam interaction and cancer onset and further progression. A search was first conducted through the COSMIC (Catalogue of Somatic Mutations in Cancer) database to identify cancer-related missense mutations positioned inside or close to the EphA2-Sam and Ship2-Sam reciprocal binding interfaces. Next, potential differences in the chemical-physical properties of mutant and wild-type Sam domains were evaluated by bioinformatics tools based on analyses of primary sequences. Three-dimensional (3D) structural models of mutated EphA2-Sam and Ship2-Sam domains were built as well and deeply analysed with diverse computational instruments, including molecular dynamics, to classify potentially stabilizing and destabilizing mutations. In the end, the influence of mutations on the EphA2-Sam/Ship2-Sam interaction was studied through docking techniques. This in silico approach contributes to understanding, at the molecular level, the mutation/cancer relationship by predicting if amino acid substitutions could modulate EphA2 receptor endocytosis.

Maternally Inherited Essential Hypertension May Be Associated with the Mutations in Mitochondrial tRNAGlu Gene.

Background: Mitochondrial DNA (mtDNA) mutations are associated with essential hypertension (EH), but the molecular mechanism remains largely unknown. Objective: The aim of this study is to explore the association between mtDNA mutations and EH. Methods: Two maternally inherited families with EH are underwent clinical, genetic and biochemical assessments. mtDNA mutations are screened by PCR-Sanger sequencing and phylogenetic, and bioinformatics analyses are performed to evaluate the pathogenicity of mtDNA mutations. We also generate cytoplasmic hybrid (cybrid) cell lines to analysis mitochondrial functions. Results: Matrilineal relatives exhibit variable degree of clinical phenotypes. Molecular analysis reveals the presence of m.A14693G and m.A14696G mutations in two pedigrees. Notably, the m.A14693G mutation occurs at position 54 in the TψC loop of tRNAGlu, a position which is critical for post-transcriptionally modification of tRNAGlu. While the m.A14696G mutation creates a novel base-pairing (51C-64G). Bioinformatic analysis shows that these mutations alter tRNAGlu secondary structure. Additionally, patients with tRNAGlu mutations exhibit markedly decreased in mtDNA copy number, mitochondrial membrane potential (MMP) and ATP, whereas the levels of reactive oxygen species (ROS) increase significantly. Conclusion: The m.A14696G and m.A14693G mutations lead to failure in tRNAGlu metabolism and cause mitochondrial dysfunction that is responsible for EH.

Peripheral blood lymphocytes differ in DNA damage response after exposure to X-rays with different physical properties.

Introduction: In radiology, low X-ray energies (<140 keV) are used to obtain an optimal image while in radiotherapy, higher X-ray energies (MeV) are used to eradicate tumor tissue. In radiation research, both these X-ray energies being used to extrapolate in vitro research to clinical practice. However, the energy deposition of X-rays depends on their energy spectrum, which might lead to changes in biological response. Therefore, this study compared the DNA damage response (DDR) in peripheral blood lymphocytes (PBLs) exposed to X-rays with varying beam quality, mean photon energy (MPE) and dose rate.Methods: The DDR was evaluated in peripheral blood lymphocytes (PBLs) by the É£-H2AX foci assay, the cytokinesis-block micronucleus assay and an SYTOX-based cell death assay, combined with specific cell death inhibitors. Cell cultures were irradiated with a 220 kV X-ray research cabinet (SARRP, X-Strahl) or a 6 MV X-ray linear accelerator (Elekta Synergy). Three main physical parameters were investigated: beam quality (V), MPE (eV) and dose rate (Gy/min). Additional copper (Cu) filtration caused variation in the MPE (78 keV, 94 keV, 118 keV) at SARRP; dose rates were varied by adjusting tube current for 220 kV X-rays (0.33-3 Gy/min) or water-phantom depth in the 6 MV set-up (3-6 Gy/min).Results: The induction of chromosomal damage and initial (30 min) DNA double-stranded breaks (DSBs) were significantly higher for 220 kV X-rays compared to 6 MV X-rays, while cell death induction was similar. Specific cell death inhibitors for apoptosis, necroptosis and ferroptosis were not capable of blocking cell death after irradiation using low or high-energy X-rays. Additional Cu filtration increased the MPE, which significantly decreased the amount of chromosomal damage and DSBs. Within the tested ranges no specific effects of dose rate variation were observed.Conclusion: The DDR in PBLs is influenced by the beam quality and MPE. This study reinforces the need for consideration and inclusion of all physical parameters in radiation-related studies.

Association of coffee and caffeine consumption with risk and prognosis of endometrial cancer and its subgroups: a Mendelian randomization.

Background: Previous studies have not established potential causal associations between coffee and caffeine consumption in endometrial cancer (EC) and its subgroups. Therefore, we used a two-sample MR method to assess the causal association between coffee and caffeine consumption and EC risk. We also evaluated the association between these genetically predicted exposures and EC prognosis. Materials and methods: This study used 12 and two independent single-nucleotide polymorphisms (SNPs) associated with coffee and caffeine consumption as instrumental variables at a genome-wide significance level of p < 5 × 10-8. The EC Association Consortium (ECAC) performed a genome-wide association study (GWAS) analysis of 12,906 cases and 108,979 controls. FinnGen Consortium performed a GWAS analysis of 1,967 EC cases and 167,189 controls. The primary technique we employed was inverse-variance weighted, followed by the weighted median, MR-Egger regression, and MR robust adjusted profile score methods. We used the MR pleiotropy residual sum, Outlier test, and MR-Egger regression to assess Outlier and pleiotropic variants. We also conducted a sensitivity analysis through the leave-one-out method. Results: Genetically predicted coffee consumption was not associated with EC and its subgroups in the ECAC, and the association was consistent in the FinnGen consortium. After excluding eight SNPs with confounding factors, the study performed sensitivity analyses, delivering consistent results. We also observed that caffeine consumption was not correlated with EC risk. As confirmed by MR analysis, selected SNPs determined that most do not significantly impact the likelihood of developing EC. Conclusion: Our study indicated no convincing evidence supports coffee and caffeine consumption causing EC or impacting its prognosis. More studies are needed to validate the results.

Negative Photoresponse Switching via Electron-Hole Recombination at The Type III Junction of MoTe2 Channel/SnS2 Top Layer.

Extensive study on 2D van der Waals (vdW) heterojunctions has primarily focused on PN diodes for fast-switching photodetection, while achieving the same from 2D channel phototransistors is rare despite their other advantages. Here, a high-speed phototransistor featuring a type III junction between p-MoTe2 channel and n-SnS2 top layer is designed. The photodetecting device operates with a basis of negative photoresponse (NPR), which originates from the recombination of photoexcited electrons in n-SnS2 and accumulated holes in the p-MoTe2 channel. For the NPR to occur, high-energy photons capable of exciting SnS2 (band gap ≈2.2 eV) are found to be effective because lower-energy photons simply penetrate the SnS2 top layer only to excite MoTe2 , leading to normal positive photoresponse (PPR) which is known to be slow due to the photogating effects. The NPR transistor showcases 0.5 ms fast photoresponses and a high responsivity over 5000 A W-1 . More essentially, such carrier recombination mechanism is clarified with three experimental evidences. The phototransistor is finally modified with Au contact on n-SnS2 , to be a more practical device displaying voltage output. Three different photo-logic states under blue, near infrared (NIR), and blue-NIR mixed photons are demonstrated using the voltage signals.

[Multiple, eruptive epithelioid hemangiomas of the scalp]. / Multiple, eruptive epitheloide Hämangiome der Kopfhaut.

Epithelioid hemangioma is a benign vascular neoplasm with a characteristic histological and immunohistochemical pattern, characterized by a lymphocytic inflammatory infiltrate with admixed eosinophils and FOS­B expression. The correct diagnosis is of particular relevance, since malignant vascular tumors with differentiated epithelioid cells can also be considered in the differential diagnosis. We present a patient with multiple epithelioid hemangiomas of the scalp accompanied by severe pain and itching. The long history of multiple therapeutic attempts illustrates the limited success of currently available treatment options.

Community- and genome-based evidence for a shaping influence of redox potential on bacterial protein evolution.

Despite deep interest in how environments shape microbial communities, whether redox conditions influence the sequence composition of genomes is not well known. We predicted that the carbon oxidation state (ZC) of protein sequences would be positively correlated with redox potential (Eh). To test this prediction, we used taxonomic classifications for 68 publicly available 16S rRNA gene sequence data sets to estimate the abundances of archaeal and bacterial genomes in river & seawater, lake & pond, geothermal, hyperalkaline, groundwater, sediment, and soil environments. Locally, ZC of community reference proteomes (i.e., all the protein sequences in each genome, weighted by taxonomic abundances but not by protein abundances) is positively correlated with Eh corrected to pH 7 (Eh7) for the majority of data sets for bacterial communities in each type of environment, and global-scale correlations are positive for bacterial communities in all environments. In contrast, archaeal communities show approximately equal frequencies of positive and negative correlations in individual data sets, and a positive pan-environmental correlation for archaea only emerges after limiting the analysis to samples with reported oxygen concentrations. These results provide empirical evidence that geochemistry modulates genome evolution and may have distinct effects on bacteria and archaea. IMPORTANCE The identification of environmental factors that influence the elemental composition of proteins has implications for understanding microbial evolution and biogeography. Millions of years of genome evolution may provide a route for protein sequences to attain incomplete equilibrium with their chemical environment. We developed new tests of this chemical adaptation hypothesis by analyzing trends of the carbon oxidation state of community reference proteomes for microbial communities in local- and global-scale redox gradients. The results provide evidence for widespread environmental shaping of the elemental composition of protein sequences at the community level and establish a rationale for using thermodynamic models as a window into geochemical effects on microbial community assembly and evolution.

Selective Induction of DNA Damage and Cell Cycle Arrest Mediated by Chromone-Triazole Dyads Derivatives: Effects on Breast and Prostate Cancer Cells.

Chromones and triazoles are groups of heterocyclic compounds widely known to exhibit a broad spectrum of biological activities. The combination of these two pharmacophores could result in multiple mechanisms of action to increase the potency of anticancer drugs and reduce their side effects. The in vitro antitumor effect of eight chromone-based compounds was evaluated in breast (T-47D and MDA-MB-231) and prostate (PC3) cancer cell lines, and in non-cancerous human mammary epithelial cells (HuMEC) using a resazurin-based method. Flow cytometry was used to evaluate the cell cycle and cell death, and É£-H2AX detection to identify DNA damage. The compounds showed selective cytotoxicity against cancer cell lines, with (E)-2-(2-(5-(4-methoxyphenyl)-2H-1,2,3-triazol-4-yl)vinyl)-4H-chromen-4-one (compound 2 a) being more potent in non-metastatic T-47D cells (IC50 0.65 µM). Replacing the hydrogen by a methyl group on the triazole ring in compound 2 b enhanced the cytotoxic activity up to IC50 0.24 µM in PC3, 0.32 µM in MDA-MB-231 and 0.52 µM in T-47D. Compound 2 b was 3-fold more potent than doxorubicin in PC3 (IC50 0.73 µM) and 4-fold in MDA-MB-231 (IC50 1.51 µM). The addition of tetrahydroisoindole-1,3-dione moiety in compound 5 did not improve its effectiveness in any of the cell lines but it exerted the lowest cytotoxic effect in HuMEC (IC50 221.35 µM). The compounds revealed different cytotoxic mechanisms: 2 a and 2 b induced G2/M arrest, and compound 5 did not affect the cell cycle.

cAMP-Epac1 signaling is activated in DDAVP-induced endolymphatic hydrops of guinea pigs

Abstract Objective To explore whether Cyclic Adenosine Monophosphate (cAMP)-Epac1 signaling is activated in 1-Desamino-8-D-arginine-Vasopressin-induced Endolymphatic Hydrops (DDAVP-induced EH) and to provide new insight for further in-depth study of DDAVP-induced EH. Methods Eighteen healthy, red-eyed guinea pigs (36 ears) weighing 200-350 g were randomly divided into three groups: the control group, which received intraperitoneal injection of sterile saline (same volume as that in the other two groups) for 7 consecutive days; the DDAVP-7d group, which received intraperitoneal injection of 10 mg/mL/kg DDAVP for 7 consecutive days; and the DDAVP-14d group, which received intraperitoneal injection of 10 μg/mL/kg DDAVP for 14 consecutive days. After successful modeling, all animals were sacrificed, and cochlea tissues were collected to detect the mRNA and protein expression of the exchange protein directly activated by cAMP-1 and 2 (Epac1, Epac2), and Repressor Activator Protein-1 (Rap1) by Reverse Transcription (RT)-PCR and western blotting, respectively. Results Compared to the control group, the relative mRNA expression of Epac1, Epac2, Rap1A, and Rap1B in the cochlea tissue of the DDAVP-7d group was significantly higher (p< 0.05), while no significant difference in Rap1 GTPase activating protein (Rap1gap) mRNA expression was found between the two groups. The relative mRNA expression of Epac1, Rap1A, Rap1B, and Rap1gap in the cochlea tissue of the DDAVP-14d group was significantly higher than that of the control group (p< 0.05), while no significant difference in Epac2 mRNA expression was found between the DDAVP-14d and control groups. Comparison between the DDAVP-14d and DDAVP-7d groups showed that the DDAVP-14d group had significantly lower Epac2 and Rap1A (p< 0.05) and higher Rap1gap (p < 0.05) mRNA expression in the cochlea tissue than that of the DDAVP-7d group, while no significant differences in Epac1 and Rap1B mRNA expression were found between the two groups. Western blotting showed that Epac1 protein expression in the cochlea tissue was the highest in the DDAVP-14d group, followed by that in the DDAVP-7d group, and was the lowest in the control group, showing significant differences between groups (p< 0.05); Rap1 protein expression in the cochlea tissue was the highest in the DDAVP-7d group, followed by the DDAVP-14d group, and was the lowest in the control group, showing significant differences between groups (p< 0.05); no significant differences in Epac2 protein expression in the cochlea tissue were found among the three groups. Conclusion DDAVP upregulated Epac1 protein expression in the guinea pig cochlea, leading to activation of the inner ear cAMP-Epac1 signaling pathway. This may be an important mechanism by which DDAVP regulates endolymphatic metabolism to induce EH and affect inner ear function. Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence Level 5.

Multiband Microstrip Rectenna Using ZnO-Based Planar Schottky Diode for RF Energy Harvesting Applications.

This paper presents a single-substrate microstrip rectenna for dedicated radio frequency energy harvesting applications. The proposed configuration of the rectenna circuit is composed of a clipart moon-shaped cut in order to improve the antenna impedance bandwidth. The curvature of the ground plane is modified with a simple U-shaped slot etched into it to improve the antenna bandwidth by changing the current distribution; therefore, this affects the inductance and capacitance embedded into the ground plane. The linear polarized ultra-wide bandwidth (UWB) antenna is achieved by using 50 Ω microstrip line and build on Roger 3003 substrate with an area of 32 × 31 mm2. The operating bandwidth of the proposed UWB antenna extended from 3 GHz to 25 GHz at -6 dB reflection coefficient (VSWR ≤ 3) and extended from both 3.5 to 12 GHz, from 16 up to 22 GHz at -10 dB impedance bandwidth (VSWR ≤ 2). This was used to harvest RF energy from most of the wireless communication bands. In addition, the proposed antenna integrates with the rectifier circuit to create the rectenna system. Moreover, to implement the shunt half-wave rectifier (SHWR) circuit, a planar Ag/ZnO Schottky diode uses a diode area of 1 × 1 mm2. The proposed diode is investigated and designed, and its S-parameter is measured for use in the circuit rectifier design. The proposed rectifier has a total area of 40 × 9 mm2 and operates at different resonant frequencies, namely 3.5 GHz, 6 GHz, 8 GHz, 10 GHz and 18 GHz, with a good agreement between simulation and measurement. The maximum measured output DC voltage of the rectenna circuit is 600 mV with a maximum measured efficiency of 25% at 3.5 GHz, with an input power level of 0 dBm at a rectifier load of 300 Ω.