Background: Malaria remains one of the major health concerns, especially in tropical countries. Although drugs such as artemisinin-based combinations are efficient for treating Plasmodium falciparum, the growing threat from multi-drug resistance has become a major challenge. Thus, there is a constant need to identify and validate new combinations to sustain current disease control strategies to overcome the challenge of drug resistance in the malaria parasites. To meet this demand, liquiritigenin (LTG) has been found to positively interact in combination with the existing clinically used drug chloroquine (CQ), which has become unfunctional due to acquired drug resistance. Purpose: To evaluate the best interaction between LTG and CQ against CQ-resistant strain of P. falciparum. Furthermore, the in vivo antimalarial efficacy and possible mechanism of action of the best combination was also assessed. Methods: The in vitro anti-plasmodial potential of LTG against CQ-resistant strain K1 of P. falciparum was tested using Giemsa staining method. The behaviour of the combinations was evaluated using the fix ratio method and evaluated the interaction of LTG and CQ by calculating the fractional inhibitory concentration index (FICI). Oral toxicity study was carried out in a mice model. In vivo antimalarial efficacy of LTG alone and in combination with CQ was evaluated using a four-day suppression test in a mouse model. The effect of LTG on CQ accumulation was measured using HPLC and the rate of alkalinization of the digestive vacuole. Cytosolic Ca2+ level, mitochondrial membrane potential, caspase-like activity, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, and Annexin V Apoptosis assay to assess anti-plasmodial potential. Proteomics analysis was evaluated by LC-MS/MS analysis. Results: LTG possesses anti-plasmodial activity on its own and it showed to be an adjuvant of CQ. In in vitro studies, LTG showed synergy with CQ only in the ratio (CQ: LTG-1:4) against CQ-resistant strain (K1) of P. falciparum. Interestingly, in vivo studies, LTG in combination with CQ showed higher chemo-suppression and enhanced mean survival time at much lower concentrations compared to individual doses of LTG and CQ against CQ-resistant strain (N67) of Plasmodium yoelli nigeriensis. LTG was found to increase the CQ accumulation into digestive vacuole, reducing the rate of alkalinization, in turn increasing cytosolic Ca2+ level, loss of mitochon-drial potential, caspase-3 activity, DNA damage and externalization of phosphatidylserine of the membrane (in vitro). These observations indicate the involvement of apoptosis-like death of P. falciparum that might be due to the accumulation of CQ. Conclusion: LTG showed synergy with CQ in the ratio LTG: CQ, 4:1) in vitro and was able to curtail the IC50 of CQ and LTG. Interestingly, in vivo in combination with CQ, LTG showed higher chemo-suppression as well as enhanced mean survival time at a much lower concentrations of both the partners as compared to an individual dose of CQ and LTG. Thus, synergistic drug combination offers the possibility to enhance CQ efficacy in chemotherapy.
Malaria remains one of the major health concerns due to the resistance of Plasmodium species toward the existing drugs warranting an urgent need for new antimalarials. Thymol derivatives were known to exhibit enhanced antimicrobial activities; however, no reports were found against Plasmodium spp. In the present study, the antiplasmodial activity of thymol derivatives was evaluated against chloroquine-sensitive (NF-54) and -resistant (K1) strains of Plasmodium falciparum. Among the thymol derivatives tested, 4-chlorothymol showed potential activity against sensitive and resistant strains of P. falciparum. 4-Chlorothymol was found to increase the reactive oxygen species and reactive nitrogen species level. Furthermore, 4-chlorothymol could perturb the redox balance by modulating the enzyme activity of GST and GR. 4-Chlorothymol also showed synergy with chloroquine against chloroquine-resistant P. falciparum. 4-Chlorothymol was found to significantly suppress the parasitemia and increase the mean survival time in in vivo assays. Interestingly, in in vivo assay, 4-chlorothymol in combination with chloroquine showed higher chemosuppression as well as enhanced mean survival time at a much lower concentration as compared to individual doses of chloroquine and 4-chlorothymol. These observations clearly indicate the potential use of 4-chlorothymol as an antimalarial agent, which may also be effective in combination with the existing antiplasmodial drugs against chloroquine-resistant P. falciparum infection. In vitro cytotoxicity/hemolytic assay evidently suggests that 4-chlorothymol is safe for further exploration of its therapeutic properties.
4-chloro eugenol (4CE), a semisynthetic analog of phytomolecule eugenol exhibited potent antiplasmodial activity with IC50 in the range of 1.5–5 μM against sensitive as well as drug resistant strain of P. falciparum. This analog also showed synergy with a clinically used antimalarial drug artesunate and was able to curtail the IC50 of artesunate up to 4–5 folds. Although, 4CE did not show any effect on heme polymerization, the most common drug target in the malaria parasite, it could increase the level of reactive oxygen species (ROS) and reactive nitrogen species (RNS) alone as well as in combination with artesunate. Further, 4CE induced oxidative stress was observed to affect the macromolecules in terms of DNA damage, protein carbonylation and lipid peroxidation. At the physiological level, cellular organelles like mitochondria and endoplasmic reticulum were observed to be get affected by 4CE in terms of membrane depolarization and calcium ion leakage respectively. These observations could be validated by expression analysis of oxidative stress responsive genes and proteins. Further, in in vivo assay, 4CE showed significant chemo-suppression of parasitemia as well as an increase in mean survival time in the murine malaria model. Interestingly, in combination with artesunate, 4CE showed higher chemo-suppression as well as enhanced mean survival time at a much lower concentrations of both the partners as compared to an individual dose of artesunate and 4CE. A combination of 4CE and artesunate was also observed to attenuate cerebral malaria pathogenesis.
Malaria eradication is still a major global health problem in developing countries, which has been of more concern ever since the malaria parasite has developed resistance against frontline antimalarial drugs. Historical evidence proves that the plants possess a major resource for the development of novel anti-malarial drugs. In the present study, the bioactivity guided fractionation of the oleogum-resin of Boswellia serrata Roxb. yielded the optimum activity in the ethyl acetate fraction with an IC50 of 22 ± 3.9 μg/mL and 26.5 ± 4.5 μg/mL against chloroquine sensitive (NF54) and resistant (K1) strains of Plasmodium falciparum respectively. Further, upon fractionation, the ethyl acetate fraction yielded four major compounds, of which 3-Hydroxy-11-keto-β-boswellic acid (KBA) was found to be the most potent with IC50 values 4.5 ± 0.60 µg/mL and 6.25 ± 1.02 μg/mL against sensitive and resistant strains respectively. KBA was found to inhibit heme detoxification pathways, one of the most common therapeutic targets, which probably lead to an increase in reactive oxygen species (ROS) and nitric oxide (NO) detrimental to P. falciparum. Further, the induced intracellular oxidative stress affected the macromolecules in terms of DNA damage, increased lipid peroxidation, protein carbonylation as well as loss of mitochondrial membrane potential. However, it did not exhibit any cytotoxic effect in VERO cells. Under in vivo conditions, KBA exhibited a significant reduction in parasitemia, retarding the development of anaemia, resulting in an enhancement of the mean survival time in Plasmodium yoelii nigeriensis (chloroquine-resistant) infected mice. Further, KBA did not exhibit any abnormality in serum biochemistry of animals that underwent acute oral toxicity studies at 2000 mg/kg body weight.
Background: The experimental knowledge of nuclear reaction data and decay properties plays a vital role in searching for novel and exotic radioisotopes, prompting us to widen the experimental study of heavy-ion induced reactions.Purpose: The aim is to study the production of mass separated (i.e., separation of different masses of residues, where each mass group consists of isobaric nuclei) evaporation residues (ERs) populated in $^{32}\mathrm{S}+^{70}\mathrm{Zn}$ and $^{32}\mathrm{S}+^{68}\mathrm{Zn}$ reactions within 115--135 and 130--150 MeV incident energy ranges, respectively, and optimization of masses 97 and 95 u that consist of $^{97}\mathrm{Pd}$, $^{97}\mathrm{Rh}$, $^{97}\mathrm{Ru}$, and $^{95}\mathrm{Pd}$, $^{95}\mathrm{Rh}$, $^{95}\mathrm{Ru}$, $^{95}\mathrm{Tc}$ isobaric residues, respectively.Method: Mass separation of ERs has been achieved at the focal plane of the Heavy Ion Reaction Analyser (HIRA) at the 15 UD Pelletron facility, IUAC, India. The residues were detected at the focal plane of HIRA using a multiwire proportional counter (MWPC).Results: Competing production of masses 97 and 95 u through the fusion of $^{32}\mathrm{S}$ ions with $^{70}\mathrm{Zn}$ and $^{68}\mathrm{Zn}$, respectively, have been observed in comparison to their neighboring masses within the measured energy range. The maximum cumulative production of $^{97}\mathrm{Ru}$ has been found to be $\ensuremath{\approx}99\ifmmode\pm\else\textpm\fi{}9.9$ $\mathrm{Bq}/\mathrm{h}\phantom{\rule{0.16em}{0ex}}\mathrm{pnA}(\mathrm{mg}/{\mathrm{cm}}^{2}$) at 125 MeV, while for $^{95}\mathrm{Ru}$ it is $\ensuremath{\approx}69\ifmmode\pm\else\textpm\fi{}6.9$ $\mathrm{Bq}/\mathrm{h}\phantom{\rule{0.16em}{0ex}}\mathrm{pnA}(\mathrm{mg}/{\mathrm{cm}}^{2}$) at 135 MeV. Comparisons of experimental results with the theoretical calculations indicate that the residues are mainly populated through the compound reaction mechanism.Conclusions: As anticipated from theory, significant yields of $^{97}\mathrm{Ru}$ and $^{95}\mathrm{Ru}$ in reactions $^{32}\mathrm{S}+^{70}\mathrm{Zn}$ and $^{32}\mathrm{S}+^{68}\mathrm{Zn}$ have been achieved via cumulative production of different isobars of mass 97 and 95 u, respectively. Cumulative yield of $^{97}\mathrm{Ru}$ has been found to be equivalent, i.e., the same order of magnitude [viz., $\ensuremath{\approx}{10}^{7}$ nuclei/h pnA(mg/${\mathrm{cm}}^{2}$)], compared to its independent production through $^{11}\mathrm{B}$ and $^{7}\mathrm{Li}$ projectile induced reactions.
We investigate the low temperature magnetic properties of a S=5/2 Heisenberg kagome antiferromagnet, the layered monodiphosphate Li_{9}Fe_{3}(P_{2}O_{7})_{3}(PO_{4})_{2}, using magnetization measurements and ^{31}P nuclear magnetic resonance. An antiferromagnetic-type order sets in at T_{N}=1.3 K and a characteristic magnetization plateau is observed at 1/3 of the saturation magnetization below T^{*}∼5 K. A moderate ^{31}P NMR line broadening reveals the development of anisotropic short-range correlations concomitantly with a gapless spin-lattice relaxation time T_{1}∼k_{B}T/ℏS, which may point to the presence of a semiclassical nematic spin-liquid state predicted for the Heisenberg kagome antiferromagnetic model or to the persistence of the zero-energy modes of the kagome lattice under large magnetic fields.
Introduction: Total pancreatectomy (TP) is indicated for multi focal PNETs. The complexity of this surgery, and morbidity related to brittle diabetes and exocrine insufficiency have prevented TP from gaining popularity in India. This report highlights the use of the 'artery first' approach to TP and subsequent outcomes in patients with multifocal PNETs at a tertiary care centre in India. Methods: A retrospective analysis of all records was done for the patients who underwent TP and they were followed up to assess the present status. Results: TP was performed in 3 patients (2 males; 22, 42, 46 years) with MEN 1 who presented with hypercalcemia and episodes of hypoglycemia for a duration between 8 - 192 months. Following multidisciplinary assessment, parathyroidectomy and thymectomy was done to achieve normocalcemia before undertaking TP. Intraoperative ultrasound was used to confirm multifocality (2-6 tumors). Pancreatic resection was approached by identifying the SMA as the first step and the pancreata were removed en bloc with the spleens. The mean duration of surgery was 430 minutes with blood loss ranging between 750 - 1800 ml. A prolonged postoperative stay (23, 35 and 40 days) was required to establish glycemic control. All 3 patients are asymptomatic on follow up (at 2, 4 and 21 months). They are on pancreatic enzyme supplements, and are euglycemic with an insulin requirement of 15, 33 and 49 units respectively. Conclusions: The 'artery first' approach is a safe and effective technique to achieve en bloc total pancreatetctomy in patients with multifocal NETs.
Security of our data is very important in current time, so to provide the security of our data should be on first priority. To conceal confidential information is very important in the present era. Steganography provides the features to conceal our confidential information into the cover medium. In this paper I used the LSB embedding technique to hide the data and also try to improve the quality of stego image with increased payload capacity. Here I am trying to provide authenticity, confidentiality, and integrity.
Steganography allows us to conceal any form of confidential data inside any cover file without getting noticed by an unknown person and not make significant changes to the cover object. Steganography is a process to hide your confidential data into a cover medium (text/image/audio/video file). In research, it is a very good area in the current years having numerous applications. This paper presents text data hiding inside a file (video) taking as a concealment vehicle by using LSB steganography with the XOR methodology. This paper presents a comparison between the basic LSB technique and the XOR methodology in a different form. The comparative analysis is done on the performance of the quality parameters MSE, PSNR, and SNR of steganography.
Steganography is a science and art of concealing the secret data using a cover medium. Cover medium can be of any type like (Text file, Audio File, Image file, and Video File) we can take any one of them to hide our secret data. Several techniques comes under the Steganography which have different pattern to hide the data. Whereas Cryptography is also an art to provide the security of your secret data by various encryption techniques. Several techniques comes under the Cryptography which have also used different methods to provide the security of data. In this paper, I am survey the combined technique used under Steganography and Cryptography through which we can prove more security to our secret data. Combination of both (Steganography and Cryptography) called metamorphic cryptography which provide a sealed and make more secure your confidential data to decrypt by the attackers.
The synthesis of 5-benzylidene bis-rhodanine derivatives are reported from bis-rhodanine (III) and different aromatic aldehydes (IV) via Knoevenagel condensation reactions. All the Derivatives (V) and (Va-m) were deep-rooted by NMR spectroscopic techniques and elemental analysis. The antiproliferative study of the compounds on HeLa human cervical cancer cell line, K562 leukemic cell line and MDAMB231 breast cancer cell line were performed by MTT assay. Docking studies were carried out against the protein HPV 16E2 present in the HeLa cell line. It show good docking scores. The results indicate that the bis-rhodanine derivatives could serve as potential molecules for the development of new anticancer agents.
A quantitative mercuric detection is very important in the environmental and biological systems. In this paper, we report a novel bis-rhodanine derived fluorescent chemosensor for recognition of Hg2+ ion in DMSO-H2O (1:1) medium. The ‘turn-on’ fluorescence response was exhibited specifically toward Hg2+ over other metal ions by receptor R2 at 410 nm, which could be ascribed to the restriction of photo-induced electron transfer (PET) process and chelation-enhanced fluorescence (CHEF) effect upon the complexation with mercury ions. The complexing stoichiometry of receptor R2 to Hg2+ was estimated to be 1:1 according to Job’s plot experiments. The limit of detection was calculated to be 7.33 × 10−7 M based on the concentration dependent emission changes with good association constant of 8.97 × 104 M−1. As a result, we express that receptor R2 is a promising candidate for Hg2+ recognition without any significant interference of other co-existing cations. The receptor R2 was successfully applied to molecular logic and keypad lock applications and real water samples to determine its potential applications.
Here we present the structural and magnetic properties of the new honeycomb material Ag3LiMn2O6. The system Ag[Li1/3Mn2/3]O-2 belongs to a quaternary 3R-delafossite family and crystallizes in a monoclinic symmetry with space group C 2/m, and the magnetic Mn4+ (S = 3/2) ions form a honeycomb network in the ab plane. An anomaly around 50 K and the presence of antiferromagnetic (AFM) coupling (Curie-Weiss temperature theta(cw) similar to -51 K) were inferred from our magnetic susceptibility data. The magnetic specific heat clearly manifests the onset of magnetic ordering in the vicinity of 48 K, and the recovered magnetic entropy, above the ordering temperature, falls short of the expected value, implying the presence of short-range magnetic correlations. An asymmetric Bragg peak (characteristic of two-dimensional order), seen in neutron diffraction, gains intensity even above the ordering temperature, thus showing the existence of short-range spin correlations. Our electron spin resonance (ESR) experiments corroborate the bulk magnetic data. Additionally, the ESR line broadening upon approaching the ordering temperature T-N could be described in terms of a BerezinskiiKosterlitz-Thouless scenario with T-KT = 40(1) K. The Li-7 NMR line shift probed as a function of temperature tracks the static susceptibility (K-iso) of magnetically coupled Mn4+ ions. The Li-7 spin-lattice relaxation rate (1/T-1) exhibits a sharp decrease below about 50 K. A critical divergence is absent at the ordering temperature perhaps because of the filtering out of the antiferromagnetic fluctuations at the Li site, i.e., at the centers of the hexagons in the honeycomb network. Combining our bulk and local probe measurements, we establish the presence of an ordered ground state for the honeycomb system Ag3LiMn2O6. Our ab initio electronic structure calculations suggest that in the ab plane, the nearest-neighbor (NN) exchange interaction is strong and AFM, while the next-NN and the third-NN exchange interactions are FM and AFM, respectively. The interplanar exchange interaction is found to be relatively small. In the absence of any frustration the system is expected to exhibit long-range, AFM order, in agreement with experiment.
It is an amplifier in which the difference between 2 input voltages is amplified, but any common voltage is suppressed. It is a most versatile building block that is used in designing of analog circuits. Highly compatible with Integrated circuit technologies, it also is serves as the input stage in a large number of operational amplifiers. In this report, current mirror load differential amplifiers of various configurations are considered. A detailed analysis of three different layouts of a differential amplifier in order to obtain better performance characteristics are shown here. The major applications of differential amplifier are as analog to digital converter & digital to analog converter. And these converters are playing an important role in computer science applications in the real world for e.g. Interfacing, implementation of computer modules etc.
We have investigated the thermodynamic and local magnetic properties of the Mott insulating system Ag3LiRu2O6 containing Ru4+ (4d(4)) for novel magnetism. The material crystallizes in a monoclinic C2/m structure with RuO6 octahedra forming an edge-shared two-dimensional honeycomb lattice with limited stacking order along the c direction. The large negative Curie-Weiss temperature (theta(CW) = -57 K) suggests antiferromagnetic interactions among Ru4+ ions, though magnetic susceptibility and heat capacity show no indication of magnetic long-range order down to 1.8 and 0.4 K, respectively. Li-7 nuclear magnetic resonance (NMR) shift follows the bulk susceptibility between 120 and 300 K and levels off below 120 K. Together with a power-law behavior in the temperature-dependent spin-lattice relaxation rate between 0.2 and 2 K, it suggest dynamic spin correlations with gapless excitations. Electronic structure calculations suggest an S = 1 description of the Ru moments and the possible importance of further neighbor interactions as well as biquadratic and ring-exchange terms in determining the magnetic properties. Analysis of our muon spin rotation data indicates spin freezing below 5 K, but the spins remain on the borderline between static and dynamic magnetism even at 20 mK.
Declining productivity of rice-wheat system in Indo–Gangetic Plains poses risk to conventional practices because of high production cost and low input use efficiency. Four crop establishment methods (CEM) and four weed management practices (WMP) were compared in a 2–year study to determine the productivity and profitability of rice-wheat system. Growth, yield traits and yields of rice was uninfluenced by CEM. Zero tillage rice (ZTR)–zero tillage wheat (ZTW) exhibited highest improvement in mean wheat yield, system productivity and profitability by 7.5%, 4.0% and 16.0%, respectively over conventional tillage rice (CTR)–conventional tillage wheat (CTW). CTR–ZTW recorded minimum total weed density and biomass in system. Post emergence application of bispyribac 25 g ha-1 + azimsulfuron 35 g ha-1 (bis + azim) in rice at 20 days after sowing (DAS)/days after transplanting (DAT); clodinofop 60 g ha-1 + carfentrazone 20 g ha-1 (clod + carf) in wheat at 30–35 DAS minimized total weed density and biomass, increased growth, productivity and profitability of the system. Results suggest that higher growth, productivity and profitability of rice–wheat system may be achieved by adoption of ZTR–ZTW with application of bis + azim in rice and clod + carf in wheat.
introduction: Diabetes mellitus is a common chronic metabolic disorder which affects millions of people. The prevalence of diabetes for all age groups worldwide was estimated to be 2.8% in 2000 and may reach 4.4% by 2030. The objective of my study was to evaluate and compare thesalivary and serum glucose levels in diabetes mellitus individuals. Material and methods: Study included 200 subjects, out of these 100 subjects were of diagnosed diabetes & 100 nondiabetic subjects were as controls group. 2ml of patient’s intra venous blood was obtained from the median cephalic vein of the forearm, by using 5 ml disposable syringe. The blood sample was transferred in a fluoride tube. Results: Glucose was present in saliva of both diabetic and non diabetic subjects. Glucose level was increased in diabetic patients. Conclusion: Concentration of glucose in saliva increases with the increase in serum glucose concentration. A significant correlation was seen between salivary and serum glucose level in diabetic as well as non diabetic subjects.
In the present work, docking studies was performed for 32 selected rhodanine derivatives and it was evaluated their binding affinity to cancer proteins (PBD ID: 2V7A and 1DTO). Molecular docking was carried out using AutoDock 4.2.2 version and the visualization result using Chimera 1.10 and Discovery Studio 4.5. Among the 32 Compounds, T3151 Abl mutant protein (PDB ID: 2V7A) Showed a better Docking Score of compounds 1a, 1l and 2h. In HPV 16 protein (PDB ID: 1DTO) compounds 1e, 2f and 2g Showed better Docking Score. Overall, among all the 32 ligands the compound 2h Showed high docking score of -9 kcal/mol against protein.
The experimental material consisting of forty advance genotypes including two checks (Rachna and Shikha) was evaluated in Randomized Block Design with three replications for eleven characters by using Mahalanobis’s D2 statistic. The clustering pattern of genotypes showed no definite relationship between genetic divergence and geographical distribution of genotypes. The genotypes were grouped into seven clusters. The maximum ten lines were put cluster IV, it had maximum intra-cluster distance while inter-cluster distance was highest between I and II. Cluster means indicated that none of the clusters was superior for all the characters studies; however hybridization between genotypes belonging to different cluster (viz. Ist and IInd) is suggested for development of superior genotypes in field pea.