MoS2/S@g-CN Composite Electrode for L-Tryptophan Sensing.

L-tryptophan (L-TRP) is an essential amino acid responsible for the establishment and maintenance of a positive nitrogen equilibrium in the nutrition of human beings. Therefore, it is vital to quantify the amount of L-tryptophan in our body. Herein, we report the MoS2/S@g-CN-modified glassy carbon electrode for the electrochemical detection of L-tryptophan (L-TRP). The MoS2/S@g-CN composite was successfully synthesized using an efficient and cost-effective hydrothermal method. The physical and chemical properties of the synthesized composite were analyzed using powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and energy-dispersive X-ray analysis (EDX). The crystallite size of the composite was calculated as 39.4 nm, with porous balls of MoS2 decorated over the S@g-CN surface. The XPS spectrum confirmed the presence of Mo, S, O, C, and N elements in the sample. The synthesized nanocomposite was further used to modify the glassy carbon (GC) electrode (MoS2/S@g-CN/GC). This MoS2/S@g-CN/GC was used for the electrochemical detection of L-TRP using cyclic voltammetry (CV) and differential pulse voltammetry (DPV) techniques. For the purpose of comparison, the effects of the scanning rate and the concentration of L-TRP on the current response for the bare GC, S@g-CN/GC, MoS2/GC, and MoS2/S@g-CN/GC were studied in detail. The MoS2/S@g-CN-modified GC electrode exhibited a rational limit of detection (LoD) of 0.03 µM and a sensitivity of 1.74 µA/ µMcm2, with excellent stability, efficient repeatability, and high selectivity for L-TRP detection.

Titanium Carbide (Ti3C2Tx) MXene as Efficient Electron/Hole Transport Material for Perovskite Solar Cells and Electrode Material for Electrochemical Biosensors/Non-Biosensors Applications.

Recently, two-dimensional (2D) MXenes materials have received enormous attention because of their excellent physiochemical properties such as high carrier mobility, metallic electrical conductivity, mechanical properties, transparency, and tunable work function. MXenes play a significant role as additives, charge transfer layers, and conductive electrodes for optoelectronic applications. Particularly, titanium carbide (Ti3C2Tx) MXene demonstrates excellent optoelectronic features, tunable work function, good electron affinity, and high conductivity. The Ti3C2Tx has been widely used as electron transport (ETL) or hole transport layers (HTL) in the development of perovskite solar cells (PSCs). Additionally, Ti3C2Tx has excellent electrochemical properties and has been widely explored as sensing material for the development of electrochemical biosensors. In this review article, we have summarized the recent advances in the development of the PSCs using Ti3C2Tx MXene as ETL and HTL. We have also compiled the recent progress in the fabrication of biosensors using Ti3C2Tx-based electrode materials. We believed that the present mini review article would be useful to provide a deep understanding, and comprehensive insight into the research status.

Transcriptional factors targeting in cancer stem cells for tumor modulation.

Cancer Stem Cells (CSCs) are now considered the primary "seeds" for the onset, development, metastasis, and recurrence of tumors. Despite therapeutic breakthroughs, cancer remains the leading cause of death worldwide. This is because the tumor microenvironment contains a key population of cells known as CSCs, which promote tumor aggression. CSCs are self-renewing cells that aid tumor recurrence by promoting tumor growth and persisting in patients after many traditional cancer treatments. According to reports, numerous transcription factors (TF) play a key role in maintaining CSC pluripotency and its self-renewal property. The understanding of the functions, structures, and interactional dynamics of these transcription factors with DNA has modified the hypothesis, paving the way for novel transcription factor-targeted therapies. These TFs, which are crucial and are required by cancer cells, play a vital function in the etiology of human cancer. Such CSC TFs will help with gene expression profiling, which provides crucial data for predicting the prognosis of patients. To overcome anti-cancer medication resistance and completely eradicate cancer, a potent therapy combining TFs-based CSC targets with traditional chemotherapy may be developed. In order to develop therapies that could eliminate CSCs, we here concentrated on the effect of TFs and other components of signalling pathways on cancer stemness.

Wetland health, water quality, and resident perceptions of declining ecosystem services: a case study of Mount Abu, Rajasthan, India.

Ecosystem services provided by wetlands are essential for communities living near wetlands, especially in an underdeveloped semi-arid landscape. The land use land cover changes and ecosystem degradation and water quality change over the past few decades have had immense effects on declining wetland ecosystem services. With the degradation, it is exerting superfluous effects on wetland communities including loss of livelihood, and decline in other wetland services like fishing, aquaculture, fuelwood, fodder, and many more. The present study attempts to assess the changing nature of wetland health, water quality, and declining ecosystem services of Mount Abu wetlands in Rajasthan, India. For assessing the change of wetland extent, we have used the remote sensing-based data for preparation of land use land cover change from 1992 to 2020. The water samples have been collected from the wetland, and different biophysical parameters of the water have been tested in the laboratory. A questionnaire-based household survey has been conducted to understand the perception of the wetland communities on the loss of ecosystem services over three decades. Further, a correlation and cluster assessment has been conducted to understand the degradation of wetland health in the selected wetlands. The study results indicated deteriorating conditions of wetland health and declining ecosystem services in the study area over the time periods. The land use land cover change analysis indicated a decrease in the spatial extent of the wetlands in the study area. Wetland communities are being affected due to the degradation of wetland health. The study recommended executing a wetland management plan for long-term conservation and livelihood management for the Mount Abu wetlands and communities.

Combinatorial Effect of Arsenic and Herbal Compounds in Telomerase-Mediated Apoptosis Induction in Liver Cancer.

Tumour illness and its resistance against existing anticancer therapies pose a serious health concern globally despite the progressive advancement of therapeutic options. The prevailing treatment of HCC using numerous antitumor agents has inflated long-lived complete remissions, but a percentage of individuals still die due to disease recurrence, indicating a need for further exploration of possible anti-tumour regimes. We aim to boost the effectiveness of the HCC treatment by conducting current investigations evaluating the effect of arsenic trioxide (ATO) with different herbal compounds like quercetin and aloe-emodin against liver tumour via inhibition of telomerase, a pro-cancer enzyme. The anticancer activity of ATO with herbal compounds was investigated in human control liver cell line (Wrl-68) and cancer liver cell line (HepG2) at different time intervals. Viability and cytotoxicity in response to combinatorial drugs were assessed in vitro by trypan blue dye exclusion assay and MTT and WST assay. Apoptosis was analysed by annexin V/PI assay, and the expression of telomerase and apoptosis-regulating proteins was evaluated by immunoblotting and qRT-PCR. Arsenic trioxide in combination with quercetin and aloe-emodin reduced cell viability in cancerous cells compared to normal cells by inducing apoptosis, downregulating telomerase and Bcl-2 (anti-apoptotic protein) and upregulating the expression of Bax (pro-apoptotic protein). ATO exhibited significant anticancer effects due to the synergistic effects of quercetin and aloe-emodin in liver tumour cells. The current study data collectively suggest that a successful inhibition of cancer growth by the combination of ATO and tested herbal medicines against liver tumour growth is via the inhibition of telomerase activity.

Fabrication of CeO2/GCE for Electrochemical Sensing of Hydroquinone.

Hydroquinone is a widely used derivative of phenol which has a negative influence on human beings and the environment. The determination of the accurate amount of hydroquinone is of great importance. Recently, the fabrication of an electrochemical sensing device has received enormous attention. In this study, we reported on the facile synthesis of cerium dioxide (CeO2) nanoparticles (NPs). The CeO2 NPs were synthesized using cerium nitrate hexahydrate as a precursor. For determining the physicochemical properties of synthesized CeO2 NPs, various advanced techniques, viz., powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), and X-ray photoelectron spectroscopy (XPS), were studied. Further, these synthesized CeO2 NPs were used for the modification of a glassy carbon electrode (CeO2/GCE), which was utilized for the sensing of hydroquinone (HQ). A decent detection limit of 0.9 µM with a sensitivity of 0.41 µA/µM cm2 was exhibited by the modified electrode (CeO2/GCE). The CeO2/GCE also exhibited good stability, selectivity, and repeatability towards the determination of HQ.

Induction of Iron Stress in Hepatocellular Carcinoma Cell Lines by Siderophore of Aspergillus nidulans Towards Promising Anticancer Effect.

Hepatocellular carcinoma is among the leading causes of cancer-related deaths worldwide and needs efficient and feasible approach of treatment. Present study focuses on exploring the anticancer activity of a secondary metabolite called siderophore of Aspergillus nidulans against hepatocellular carcinoma cell line HepG2. These small peptides are produced by microorganisms including fungi for scavenging iron from its surroundings. Fungi including Aspergillus spp. are known to produce siderophores under iron-limited conditions. Siderophores have high affinity towards iron and are classified into various types. In the present study, siderophore isolated and purified from fungal cultures was confirmed to be of hydroxamate type by chrome azurol sulfonate and Atkin's assay. HPLC analysis confirmed purity while LC-ESI-MS revealed that the siderophore is triacetyl fusigen. Cancerous cells, HepG2, grown under siderophore treatment showed inhibition in growth and proliferation in a dose- and time-dependent manner. Reduction in viability and metabolic activity was evident upon treatment as seen in trypan blue, MTT and WST assay. Fluorescent staining using PI and DAPI confirmed the same while DCFDA staining revealed increased reactive oxygen species production which might have led to cell death and deterioration. Such increase in ROS has been correlated with iron accumulation by assessing intracellular iron level through ICP-MS. To assess the effect of siderophore treatment on normal cells, WRL-68, same assays were carried out but the effect was mostly non-significant up to 48 h. Thus, present work suggests that an optimum dose of siderophore purified from A. nidulans culture might prove a useful anticancer agent.

Serial profile of flow-mediated dilatation in primigravida for prediction of preeclampsia and gestational hypertension.

OBJECTIVE: Assessment of endothelial dysfunction for prediction of gestational hypertension/preeclampsia (GH/PE). METHODS: Serial assessment of flow-mediated vasodilatation (FMD) of brachial artery was done in first, second, and third trimesters, and within 6 weeks of delivery in primigravida (n = 654). Logistic regression was used to assess the predictive value of FMD for the development of GH/PE. RESULTS: Significant fall in FMD was observed from first trimester to third trimester but decrease in FMD in GH/PE group (57%) was more marked as compared to normal (39%) (p < 0.01). FMD (third trimester) was able to predict the development of GH/PE (OR = 1.303; 95% CI 1.088-1.562; p = 0.004). CONCLUSIONS: FMD can be used as a non-invasive marker to predict the development of GH/PE.

Immunomodulatory Role of Arsenic in Regulatory T Cells.

BACKGROUND AND OBJECTIVE: Chronic Arsenic (As) exposure continued to be a cause of major problem associated with different kind of diseases including skin problem and different types of cancer. As exposure leads to numerous other pathological conditions that affect millions of people worldwide on a regular basis. It was recently established that As toxicity affects immune system and modulates the function and survival of cells involved in immune regulation. Arsenic trioxide (As2O3) was reported to be an effective apoptosis inducer in a variety of cell types. Despite intensive research, the exact immune-modulatory role of As is poorly understood till now. METHODS: We reviewed the immunological imbalance caused due to As exposure and focused on regulatory T cells (Tregs cells). In this review, we mainly focused on role of As and its potential mechanisms in the induction and modulation of Tregs cells. CONCLUSION: The multiple effects of As on immune system tend to decrease the immune surveillance system and increase the rate of infection, autoimmune disease, cancer and other immune mediated problems. As exposed individuals showed induction of oxidative stress, inflammation and impaired lymphocytes activation. The effect of As on T cell population is mainly attributed to altered expression of key immune regulator molecules impaired T cell functions, cytokines production, induction of apoptosis, and oxidative stress induction in T cells.

Population Pharmacokinetics of LY2623091 in Patients With Hypertension and Chronic Kidney Disease.

LY2623091 is a selective, orally active, nonsteroidal, competitive mineralocorticoid receptor antagonist that blocks the actions of aldosterone and other mineralocorticoid receptor ligands at the receptor level. The aim of this work was to explore and establish a population pharmacokinetic model, quantify the degree of interindividual variability, and identify significant disease-, patient-, and study-specific covariates that alter the disposition of LY2623091. The data included concentrations from 294 healthy subjects and patients with hypertension and/or chronic kidney disease (CKD), sampled in 5 phase 1 and 2 studies. The pharmacokinetics of LY2623091 was well described by a 2-compartment model with first-order absorption and elimination. Formulation (on oral bioavailability) as well as weight and age (both on apparent central volume of distribution) were found to be significant covariates. The relative bioavailability of the capsule formulation was 68.4% compared to that of the solution. Hypertension and CKD status were not significant covariates. The pharmacokinetic model suggests that given the same dose, patients with hypertension and/or CKD would receive a similar exposure compared to subjects without these disease conditions.

Lack of pharmacokinetic drug-drug interaction between ramucirumab and irinotecan in patients with advanced solid tumors.

PURPOSE: The objective of this phase II study was to evaluate the potential of pharmacokinetic (PK) drug-drug interactions between ramucirumab and irinotecan or its metabolite, SN-38, when administered with folinic acid and 5-fluorouracil (FOLFIRI). METHODS: Patients received intravenous infusions of FOLFIRI and ramucirumab 8 mg/kg on Day 1 of a 2-week cycle. FOLFIRI was administered alone in Cycle 1; ramucirumab followed by FOLFIRI was administered in all subsequent cycles. Blood was collected at regular intervals after infusions in Cycles 1 and 2 to determine irinotecan, SN-38, and ramucirumab concentrations. PK parameters were derived by noncompartmental analysis. RESULTS: Twenty-nine patients received treatment. The dose-normalized area under the concentration versus time curve from zero to infinity [AUC(0-∞)] and the maximum observed concentration (C max) of irinotecan and SN-38 were comparable between Cycle 1 (FOLFIRI alone) and Cycle 2 (ramucirumab + FOLFIRI). The ratios of geometric least squares (LS) means for irinotecan were 0.93 (90 % CI 0.83-1.05) for AUC(0-∞) and 1.04 (90 % CI 0.97-1.12) for C max. The ratios of geometric LS means for SN-38 were 0.95 (90 % CI 0.88-1.04) for AUC(0-∞) and 0.97 (90 % CI 0.85-1.12) for C max. The most common treatment-emergent adverse events, regardless of grade, were fatigue (19 patients, 65.5 %), diarrhea, (16 patients, 55.2 %), and neutropenia (15 patients, 51.7 %). Grade ≥3 neutropenia was reported in 7 (24.1 %) patients. CONCLUSIONS: There was no PK drug-drug interaction between ramucirumab and irinotecan or its metabolite, SN-38. Ramucirumab with FOLFIRI was well tolerated in this study, with no new safety concerns.

Lack of pharmacokinetic drug-drug interaction between ramucirumab and paclitaxel in a phase II study of patients with advanced malignant solid tumors.

PURPOSE: The objective of this phase II study was to evaluate pharmacokinetic interaction potential between ramucirumab and paclitaxel in patients with advanced cancer. METHODS: This study was designed to assess 2-way pharmacokinetic drug-drug interactions between ramucirumab and paclitaxel. Twenty-four patients participated in Part A, which consisted of a 2-week monotherapy period in which paclitaxel 80 mg/m(2) was administered on day 1, followed by a 4-week cycle of combination treatment with ramucirumab (8 mg/kg on days 1 and 15; paclitaxel on days 1, 8, and 15). Patients could continue to receive combination therapy with ramucirumab and paclitaxel. In 16 patients in Part B, ramucirumab monotherapy was administered on day 1 of a 3-week cycle. Patients could continue to receive ramucirumab monotherapy or combination therapy with paclitaxel. RESULTS: Concomitant administration of ramucirumab had no effect on pharmacokinetics of paclitaxel, with ratios of geometric least squares (LS) means (with ramucirumab vs. alone) of 1.09 (90 % confidence interval [CI] 0.93, 1.29) for AUC(0-∞) and 0.97 (90 % CI 0.83, 1.13) for C max. In addition, similar ramucirumab pharmacokinetic characteristics were observed with or without paclitaxel administration. The ratios of geometric LS means of AUC(0-∞) and C max of ramucirumab (with paclitaxel vs. alone) were 1.00 (90 % CI 0.84, 1.19) for AUC(0-∞) and 1.07 (90 % CI 0.93, 1.24) for C max, respectively. CONCLUSIONS: Concomitant paclitaxel administration is unlikely to affect the pharmacokinetics of ramucirumab, and vice versa. The incidence and severity of adverse events were consistent with the known safety profiles of paclitaxel and ramucirumab.

Evaluation of the effect of necitumumab on the corrected QT interval in patients with advanced solid tumors.

PURPOSE: Necitumumab is a second-generation, recombinant, human immunoglobulin G1 monoclonal antibody that blocks the ligand binding site of the epidermal growth factor receptor. The primary objective of this phase 2 study, conducted in accordance with International Conference on Harmonisation E14 guidance, was to determine the effect of necitumumab treatment on QT/QTc interval in patients with advanced solid tumors. METHODS: Patients received necitumumab monotherapy at an absolute dose of 800 mg, once per week for each 6-week cycle. Triplicate electrocardiogram readings were taken at pretreatment (baseline) and then weekly at multiple timepoints that were time-matched with blood samples to determine necitumumab concentrations. RESULTS: Seventy-five patients received treatment. Overall, the upper bound of the two-sided 90 % confidence interval for mean change from baseline in QTc in cycle 1 did not exceed 10 ms. No patients had a mean QTcF interval >500 ms, and no patients had an increase of >60 ms. Necitumumab concentration-QTc analysis also showed that necitumumab is unlikely to cause QTc prolongation. CONCLUSIONS: The results demonstrate lack of effect of necitumumab on the QTc interval in heavily pretreated patients with advanced solid tumors, suggesting that QT prolongation is not a major safety concern for necitumumab at the recommended therapeutic dose. The safety profile was consistent with the known safety profile of necitumumab.

Isolation of a metastable intermediate in a heterometallic Cu(II)-Hg(II) 1D polymeric chain: synthesis, crystal structure, and photophysical properties.

A metastable heterometallic intermediate, [Cu2(bpy)2(DIPSA)2Hg2(OAc)4(DIPSA)2]n (1, where OAc = CH3COO(-), bpy = bipyridine, and DIPSA = diisopropylsalicylic acid), has been isolated and characterized during the synthesis of 1D polymer [Cu2(bpy)2(DIPSA)2(CH3CN)2Hg2(OAc)2(DIPSA)4]n (2) at ambient temperature in acetonitrile. Moreover, recrystallization of 2 in methanol results in monomeric [Cu(DIPSA)(bpy)(CH3OH)]·CH3OH (3). Complexes 1-3 have been characterized by elemental analysis, Fourier transform infrared, and UV-vis spectroscopy as well as by their single-crystal X-ray structures. The photophysical study suggests the quenching of fluorescence of DIPSA upon complexation.

Molecular precursors for the preparation of homogenous zirconia-silica materials by hydrolytic sol-gel process in organic media. Crystal structures of [Zr{OSi(O(t)Bu)3}4(H2O)2]·2H2O and [Ti(O(t)Bu){OSi(O(t)Bu)3}3].

[Zr(OPr(i))(4)·Pr(i)OH] reacts with [HOSi(O(t)Bu)(3)] in anhydrous benzene in 1:1 and 1:2 molar ratios to afford alkoxy zirconosiloxane precursors of the types [Zr(OPr(i))(3){OSi(O(t)Bu)(3)}] (A) and [Zr(OPr(i))(2){OSi(O(t)Bu)(3)}(2)] (B), respectively. Further reactions of A or B with glycols in 1:1 molar ratio afforded six chemically modified precursors of the types [Zr(OPr(i))(OGO){OSi(O(t)Bu)(3)}] (1A-3A) and [Zr(OGO){OSi(O(t)Bu)(3)}(2)] (1B-3B), respectively [where G = (-CH(2)-)(2) (1A, 1B); (-CH(2)-)(3) (2A, 2B) and (-CH(2)CH(2)CH(CH(3)-)} (3A, 3B)]. The precursors A and B are viscous liquids, which solidify on ageing whereas the other products are all solids, soluble in common organic solvents. These were characterized by elemental analyses, molecular weight measurements, FAB mass, FTIR, (1)H, (13)C and (29)Si-NMR studies. Cryoscopic molecular weight measurements of all the products, as well as the FAB mass studies of 3A and 3B, indicate their monomeric nature. However, FAB mass spectrum of the solidified B suggests that it exists in dimeric form. Single crystal structure analysis of [Zr{OSi(O(t)Bu)(3)}(4)(H(2)O)(2)]·2H(2)O (3b) (R(fac) = 11.9%) as well as that of corresponding better quality crystals of [Ti(O(t)Bu){OSi(O(t)Bu)(3)}(3)] (4) (R(fac) = 5.97%) indicate the presence of a M-O-Si bond. TG analyses of 3A, B, and 3B indicate the formation of zirconia-silica materials of the type ZrO(2)·SiO(2) from 3A and ZrO(2)·2SiO(2) from B or 3B at low decomposition temperatures (≤200 °C). The desired homogenous nano-sized zirconia-silica materials [ZrO(2)·nSiO(2)] have been obtained easily from the precursors A and B as well as from the glycol modified precursors 3A and 3B by hydrolytic sol-gel process in organic media without using any acid or base catalyst, and these were characterized by powder XRD patterns, SEM images, EDX analyses and IR spectroscopy.

Wettability of Y2O3: A Relative Analysis of Thermally Oxidized, Reactively Sputtered and Template Assisted Nanostructured Coatings.

The wettability of reactively sputtered Y2O3, thermally oxidized Y-Y2O3 and Cd-CdO template assisted Y2O3 coatings has been studied. The wettability of as-deposited Y2O3 coatings was determined by contact angle measurements. The water contact angles for reactively sputtered, thermally oxidized and template assisted Y2O3 nanostructured coatings were 99°, 117° and 155°, respectively. The average surface roughness values of reactively sputtered, thermally oxidized and template assisted Y2O3 coatings were determined by using atomic force microscopy and the corresponding values were 3, 11 and 180 nm, respectively. The low contact angle of the sputter deposited Y2O3 and thermally oxidized Y-Y2O3 coatings is attributed to a densely packed nano-grain like microstructure without any void space, leading to low surface roughness. A water droplet on such surfaces is mostly in contact with a solid surface relative to a void space, leading to a hydrophobic surface (low contact angle). Surface roughness is a crucial factor for the fabrication of a superhydrophobic surface. For Y2O3 coatings, the surface roughness was improved by depositing a thin film of Y2O3 on the Cd-CdO template (average roughness = 178 nm), which resulted in a contact angle greater than 150°. The work of adhesion of water was very high for the reactively sputtered Y2O3 (54 mJ/m²) and thermally oxidized Y-Y2O3 coatings (43 mJ/m²) compared to the Cd-CdO template assisted Y2O3 coating (7 mJ/m²).

Disposition and metabolism of semagacestat, a {gamma}-secretase inhibitor, in humans.

Semagacestat is a functional gamma-secretase inhibitor that has been shown to reduce the rate of formation of amyloid-beta in vitro and in vivo. This study was conducted to characterize the disposition of semagacestat in humans. After a single 140-mg dose of [(14)C]semagacestat administered as an oral solution to six healthy male subjects, semagacestat was rapidly absorbed (T(max) approximately 0.5 h) and eliminated from the systemic circulation (terminal t(1/2) approximately 2.4 h). The major circulating metabolites of semagacestat, M2 (hydrolysis of the amide bond proximal to the benzazepine ring) and M3 (benzylic hydroxylation of the benzazepine ring), accounted for approximately 27 and 10% of total radioactivity exposure, respectively, as calculated from relative area under the plasma concentration versus time curve from 0 to 24 h derived from the plasma radiochromatograms. The radioactive dose was almost completely recovered after 7 days postdose, with 87% of the dose in urine and 8% in feces. Unchanged [(14)C]semagacestat in urine accounted for approximately 44% of the dose, which indicates that renal excretion played an important role in elimination. Metabolites M2 and M3, with their related secondary metabolites, each accounted for approximately 20% of the dose in excreta. In vitro data indicate the formation of M3 is primarily mediated by CYP3A, with cDNA-expressed CYP3A5 approximately 2 times more efficient than CYP3A4 in forming M3. Thus, the relative content of CYP3A4 and CYP3A5 in humans will likely determine the formation clearance of M3 after exposure to semagacestat.