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Understanding and analysis of antennas is crucial for the development of modern telecommunication technologies, like 5G or massive MIMO. Research in this area has the need for software to measure, analyze and test antenna systems. For instance, one needs a convenient way to transform large amounts of antenna measurement data into a concise representation. The herein described eadf package aims at providing this functionality. On top of that, it offers routines to interpolate the beam-pattern of an antenna as well as compressing it in spatial frequency domain. As such, it can be used for the development of high resolution parameter estimation algorithms and analysis of antenna beam-patterns. In summary, the package provides a flexible and extensible framework for dealing with antennas.

Conventional techniques for detecting Cd, such as [e.g., atomic absorption spectrometry (AAS), inductively coupled plasma-mass spectrometry (ICP-MS)], often require expensive equipment, extensive sample preparation or specialized expertise. This novel research demonstrates how to customize an effective optical biosensor to detect low Cadmium (Cd) ion levels in milk samples. Compared to the previous report's detection limit of 8.1 μg/L, this unique approach shows a lower limit of 4.8 μg/L. Such fabricated optical biosensor was designed to monitor urease activity to detect Cd ions in milk samples, where calibration was performed using UV–Vis spectroscopy and further validation was done using ICP-MS technology. In this process, the urease enzyme was extracted from the jack bean, which was further immobilized using EDC-NHS coupling for the functionalization, thus optimizing stability and reactivity. An activity assay was performed for immobilized urease at pH 7.5; the optimized enzyme was 67 % stable for up to four weeks of storage at 4 °C due to excellent crosslinking during functionalization and immobilization. The coefficient of determination (R2) was calculated to measure the proportion of biosensor readings with standard readings obtained by the ICP-MS readings. The proposed method obtained a moderate R2 value close to 1, i.e., 0.88674, indicating a moderate agreement between ICMP readings and the proposed biosensor readings. Remarkably, the optical biosensor exhibits great stability and efficiency in detecting Cd ions in milk as low as 4.8 μg/L. FESEM and FTIR spectroscopy were used to examine the morphological and structural properties of the immobilized enzyme. The findings imply that the intended optical biosensor can be employed for on-field detection.

Crystal orientation plays a crucial role in the performance of Sb2S3 thin-film solar cells (TFSCs). Among various deposition techniques, vapor transport deposition (VTD) stands out as a viable technique for producing scalable and uniformly deposited thin films, particularly in the solar industry. This study explores temperature-modulated VTD-Sb2S3 deposition to enable efficient carrier transport in photovoltaic cells. In the VTD process, the deposition temperature is altered between 480 °C and 540 °C. XRD, SEM, EDS, and AFM techniques are employed to obtain the characteristics of the Sb2S3 thin films at varying temperatures and evaluate critical features like crystal structure and orientation, surface morphology, composition, and roughness. The prominent crystal orientation changes from the (hk0) to the (hk1) plane after increasing the deposition temperature from 500 to 520 °C. The (211)- and (221)-planes become more prominent when the deposition temperature exceeds 520 °C. The device with the architecture SLG/Mo/Sb2S3/CdS/i-ZnO/AZO/Al, a substrate-configured TFSC, yields a maximum power conversion efficiency of 0.22% when the VTD-Sb2S3 absorber film is deposited at 520 °C. This study presents a promising approach to producing thin films with a preference for specific crystal orientations. The primary aim is to enhance the efficiency of solar cells that utilize VTD-Sb2S3 absorbers.

Rationale & Objective: Dialysis comes with a substantial treatment burden, so patients must select care plans that align with their preferences. We aimed to deepen the understanding of decisional regret with dialysis choices. Study Design: This study had a mixed-methods explanatory sequential design. Setting & Participants: All patients from a single academic medical center prescribed maintenance in-center hemodialysis or presenting for home hemodialysis or peritoneal dialysis check-up during 3 weeks were approached for survey. A total of 78 patients agreed to participate. Patients with the highest (15 patients) and lowest decisional regret (20 patients) were invited to semistructured interviews. Predictors: Decisional regret scale and illness intrusiveness scale were used in this study. Analytical Approach: Quantitatively, we examined correlations between the decision regret scale and illness intrusiveness scale and sorted patients into the highest and lowest decision regret scale quartiles for further interviews; then, we compared patient characteristics between those that consented to interview in high and low decisional regret. Qualitatively, we used an adapted grounded theory approach to examine differences between interviewed patients with high and low decisional regret. Results: Of patients invited to participate in the interviews, 21 patients (8 high regret, 13 low regret) agreed. We observed that patients with high decisional regret displayed resignation toward dialysis, disruption of their sense of self and social roles, and self-blame, whereas patients with low decisional regret demonstrated positivity, integration of dialysis into their identity, and self-compassion. Limitations: Patients with the highest levels of decisional regret may have already withdrawn from dialysis. Patients could complete interviews in any location (eg, home, dialysis unit, and clinical office), which may have influenced patient disclosure. Conclusions: Although all patients experienced disruption after dialysis initiation, patients’ approach to adversity differs between patients experiencing high versus low regret. This study identifies emotional responses to dialysis that may be modifiable through patient-support interventions. Plain-Language Summary: As part of a quality improvement initiative in our dialysis practice, a patient stated, “I wish I never started dialysis.” This quote served as the catalyst for embarking on a research project with the aim to understand why patients living with end-stage kidney disease have regret about starting and continuing dialysis, a lifesaving but time-intensive measure. We surveyed and interviewed patients on the topic and learned that patients experiencing regret had a disrupted sense of self and blamed themselves for their need of dialysis. Patients with little to no regret demonstrated positivity and self-compassion. These findings will help health care professionals as they work with patients considering dialysis or having newly started dialysis.

The COVID-19 pandemic has adversely affected the transportation sector, leading to a change in travel behavior. One of the most important responses of countries worldwide to slow the spread of the pandemic has been to restrict the movement of people, which has had a considerable effect on transport systems and is likely to affect the modal choices of commuters. The social and economic effects of the COVID-19 epidemic on public transportation encompass beyond service performance and health risks to social equity, financial viability, and sustainable mobility. To assess the likely nature of such a shift, this study attempts to understand mode choice based on the perception of commuters for their work and non-work trips after the lockdown phase due to COVID-19. The Multinomial Logit Model was used in this study to find the association of mode choice with health-related safety perceptions of commuters for private and public transport, and their socio-economic and travel characteristics. Mode choice for private transport was found for work trips, whereas non-motorized transport for non-work (shopping, leisure, etc.) trips up to a distance of 10 km. The model results showed that significant factors for the increase in the usage of private transport and non-motorized transport relative to public transport were physical distancing and hygiene. This study provides results for future transportation policies in the post-COVID period. The results, like emerging positive perceptions of non-motorized modes, are very useful for making better investments in the country to promote sustainable transportation and articulating solutions to address high-risk perceptions associated with public transport modes.

Background: Intracortical microstimulation (ICMS) of somatosensory cortex can partially restore the sense of touch. Though ICMS bypasses much of the neuraxis, prior studies have found that conscious detection of touch elicited by ICMS lags behind the detection of cutaneous vibration. These findings may have been influenced by mismatched stimulus intensities, which can impact temporal perception. Objective: Evaluate the relative latency at which intensity-matched vibration and ICMS are perceived by a human participant. Methods: One person implanted with microelectrode arrays in somatosensory cortex performed reaction time and temporal order judgment (TOJ) tasks. To measure reaction time, the participant reported when he perceived vibration or ICMS. In the TOJ task, vibration and ICMS were sequentially presented and the participant reported which stimulus occurred first. To verify that the participant could distinguish between stimuli, he also performed a modality discrimination task, in which he indicated if he felt vibration, ICMS, or both. Results: When vibration was matched in perceived intensity to high-amplitude ICMS, vibration was perceived, on average, 48 ms faster than ICMS. However, in the TOJ task, both sensations arose at comparable latencies, with points of subjective simultaneity not significantly different from zero. The participant could discriminate between tactile modalities above chance level but was more inclined to report feeling vibration than ICMS. Conclusions: The latencies of ICMS-evoked percepts are slower than their mechanical counterparts. However, differences in latencies are small, particularly when stimuli are matched for intensity, implying that ICMS-based somatosensory feedback is rapid enough to be effective in neuroprosthetic applications.

In India, auto rickshaws are the most convenient and cheapest mode of near-to-door transport in both rural and urban areas. Such vehicles powered with internal combustion engines (ICEs) are one of the main sources of pollutants on urban corridors. One way to minimize tail-pipe emissions is to use electric motors in place of ICE. To evaluate the vehicle performance, energy consumption, driving behavior, optimal design and management of such electric vehicles, driving cycle is an important tool. So far, only limited studies exist on the development of a driving cycle for e-rickshaw. Moreover, these studies are concentrated in urban traffic environment and research accounting rural and urban environment together remain unexplored. In this study, real world driving data for 100 trips of e-rickshaw are collected on a road stretch passing through rural and urban setting. A high-end GPS data logger was used to collect vehicle kinematics such as continuous speed profile, acceleration/deceleration, heading, and vehicle position coordinates. Nine different driving characteristics representing actual traffic conditions are identified and used for developing e-rickshaw driving cycle (ERDC). Two approaches, random selection and k-means clustering are explored to arrive at best representative ERDC using micro-trips technique. The analysis results revealed that k-means clustering outperforms the random selection method with additional benefit of accounting traffic conditions systematically. The insights from this study can be used to understand and model the performance of e-rickshaw, in terms of energy consumption and driving characteristics, compared to other fossil-fuel driven automobiles.

The outbreak of COVID-19 pandemic has resulted in change in both commute and personal travel patterns. Though, in India, lockdown was implemented from 25th March 2020, due to self-awareness and pandemic risk perception, change in commuter behavior was observed from the beginning of March 2020. The period from 15th to 24th March 2020 is considered as the transition phase of COVID-19 outbreak in India (i.e., between no lockdown and lockdown period). This study attempts to use a decision tree approach to investigate the modal preference of 1542 commuters in association with socio-economic and travel characteristics, and safety perceptions with respect to public and private modes during transition to lockdown due to COVID-19 in India. About 41% of commuters stopped traveling during the transition to lockdown phase, 51.3% were using the same mode of transport and 5.3% of commuters shifted from public to private mode. The study findings reported different interactions of factors influencing the decision to use public or private modes of transport for daily commuting during pandemic situations like COVID-19. Interestingly, safety perceptions (associated with personal health) of commuters did not play a significant role in their mode choice behavior during the transition phase. Though people perceived public transportation as unsafe over personal vehicle use, the actual commute patterns did not validate this due to a possible reason that commuters do not have enough alternative modes. Given the uncertainties in the decision making of the commuters regarding their travel behavior due to physical distancing, the insights from this study are important to policymakers and local transport authorities to understand the change in travel patterns.

Hugonia mystax Linn. a woody evergreen plant locally known as Modirakanni has been used in primary health care by tribals from Tiruvannamalai hills, Tamil Nadu, India. Ethnobotanically, the plant parts are used for rheumatism, skin diseases and inflammation. However, there is no data on active phytoconstituents in stem-bark and root mainly contributing to biological activities. In the present study an attempt has been made to quantify plant phenolics from aqueous, ethanolic and methanolic extracts of stem-bark and root of H. mystax. The extracts were also evaluated for their free radical scavenging potential. Quantitative determination of total phenolic content, total flavonoid content and DPPH free radical scavenging activity of plant extracts were carried out using colorimetric methods. Quantitative determination of individual phenolic compounds such as gallic acid, catechol, caffeic acid, vanillin, p-coumaric acid and ferulic acid in stem-bark and roots extracts were analyzed using RP-HPLC. The highest phenolic content was found in ethanol extract of root (262.2 ± 0.96 μg of gallic acid equivalent (GAE)/mg of dry plant material), whereas, the highest amount of flavonoids content was found in aqueous extract of root (18.06 ± 1.25 μg of quercetin equivalent (QE)/mg of dry plant material). Q. The highest amount of phenolic acid present was p-coumaric acid (3.775 mg/g of dry plant material) in methanol extract of stem-bark. All the solvent extracts of stem-bark and root have shown the presence of p-coumaric acid. Methanol extracts of stem-bark and root with IC50 values of 175.48 ± 2.14 μg/ml and 169.15 ± 1.10 μg/ml respectively, show potent free radical scavenging activity. In conclusion it can be said that, the plant is rich in phenolics and the major component p-coumaric acid may probably be responsible for the traditional claims of its biological activities. However, the mechanism of action of the active plant extracts needs to be investigated at the molecular level. Keywords: Hugonia mystax, Reverse phase-high performance liquid chromatography, Total phenolic content, Total flavonoid content

In the past decade, water scarcity has become major concern and is going to be reality in future too. At the same time textile is necessity which needs a billion liters of fresh water for its processing. Out of this 16 % of water is only used for dyeing of textile materials. In a quest to develop a sustainable approach to reduce water scarcity, an attempt has been made to minimize water consumption in textile wet processing. In this work, an eco-friendly glycerine based eutectic solvent (GES) was prepared by using choline chloride, urea and glycerin to reduce water consumption in polyester dyeing. The prepared solvent was characterized in terms of FTIR. Dyeing parameters like time, temperature and pH were optimized for dyeing of polyester using GES as a dyeing medium. The efficacy of dyeing was analyzed by colour strength and colour performance properties; sublimation, wash and light fastness. In comparison with conventional dyed polyester overall dyeing performance was found to be better without affecting tensile strength of polyester which remains almost same whereas thermal stability of solvent dyed polyester was slightly improved compared with aqueous dyed polyester. The results obtained from this study suggest that the GES as a polyester dyeing medium can be a green approach in dyeing of polyester.

Introduction: Mesenchymal stem cells (MSCs) possess endogenous reparative properties and may serve as an exogenous therapeutic intervention in patients with chronic kidney disease. Cardiovascular risk factors clustering in the metabolic syndrome (MetS) might adversely affect cellular properties. To test the hypothesis that Mets interferes with MSC characteristics, we performed comprehensive comparison of the mRNA, microRNA, and protein content of MSCs isolated from Lean and MetS pigs. Methods: Domestic pigs were fed a 16-week Lean or MetS diet (n = 4 each). Expression profiles of co-existing microRNAs, mRNAs, and proteins were obtained by high-throughput sequencing and liquid chromatography-mass spectrometry. TargetScan and ComiR were used to predict target genes of differentially expressed microRNAs, and DAVID 6.7 for functional annotation analysis to rank primary gene ontology categories for the microRNA target genes, mRNAs, and proteins. Results: Differential expression analysis revealed 12 microRNAs upregulated in MetS-MSCs compared to Lean-MSCs (fold change>1.4, p

Homogenates of some rat tissues, incubated in Tris-maleate buffer containing bovine serum albumin, olive oil emulsion, heparin, and serum, liberated free fatty acids. The total lipolytic activity in tissues of rats fed a low fat, 20% lard, or 20% corn oil diet for 6 wk was measured.Similar activities were found in all the livers, but there was a significant increase in the total lipolytic activity of the mucosa, epididymal fat, and mesenteric tissues after ingestion of an unsaturated fat diet as compared with that containing a more saturated fat. From measurements of the lipolytic activity in the presence of 1 m NaCl or 0.2 m NaF and in the absence and presence of heparin and serum, the conclusion is drawn that more lipoprotein lipase was present in adipose tissue of rats on unsaturated fat diets.An increase in available lipoprotein lipase after unsaturated fat diets may aid in clearing lipids from the blood of these rats and thus in producing the lower blood lipid levels obtained.

Frequent resuspension of sediments in the water column hampers photosynthesis in submerged aquatic vegetation due to decreased light, reduces gas exchange from sediment deposition and affects their anchoring ability. Remote sensing of light attenuation of the water column in form of diffuse attenuation coefficient of downwelling photosynthetically available radiation (K dPAR ) provides a spatial perspective to study light attenuation of water column. This study aims to use Sentinel-2 derived K dPAR to characterize light variation and test its significance in relation to occurrence of eelgrass (Zostera marina) at Horsens and Roskilde fjords located in coastal waters of Denmark. Areas with maximum of K dPAR (mean > 75 th percentile) coinciding with maximum and minimum variation (standard deviation >75 th and <25 th percentile respectively) were identified at the study sites. The standard deviation (SD) of K dPAR and fraction of surface irradiance reaching bottom (PAR Z ) was used to predict occurrences of eelgrass using Logistic regression (LR) and Support Vector Machine (SVM). The LR and SVM (linear kernel) could predict eelgrass presence-absence with 65 % overall accuracy and precision of 63 % and 62 % respectively on the test set (n = 238). SD correlation with eelgrss occurrences (Point-biserial correlation = -0.11, p = 0.002) and with predicted probabilities of logistic regression (Pearson's r = -0.46) indicates increased K dPAR variation reduces chances of eelgrass. The K dPAR for this study was derived using Quasi Analytical Algorithm Version-5 (QAA-V5) and Case-2 Regional Coast Colour (C2RCC) and validated against in-situ matched observations (n = 113) for duration of March to October of 2016-2018., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

Messenger RNA (mRNA) has gained marvelous attention for managing and preventing various conditions like cancer, Alzheimer's, infectious diseases, etc. Due to the quick development and success of the COVID-19 mRNA-based vaccines, mRNA has recently grown in prominence. A lot of products are in clinical trials and some are already FDA-approved. However, still improvements in line of optimizing stability and delivery, reducing immunogenicity, increasing efficiency, expanding therapeutic applications, scalability and manufacturing, and long-term safety monitoring are needed. The delivery of mRNA via a nanocarrier system gives a synergistic outcome for managing chronic and complicated conditions. The modified nanocarrier-loaded mRNA has excellent potential as a therapeutic strategy. This emerging platform covers a wide range of diseases, recently, several clinical studies are ongoing and numerous publications are coming out every year. Still, many unexplained physical, biological, and technical problems of mRNA for safer human consumption. These complications were addressed with various nanocarrier formulations. This review systematically summarizes the solved problems and applications of nanocarrier-based mRNA delivery. The modified nanocarrier mRNA meaningfully improved mRNA stability and abridged its immunogenicity issues. Furthermore, several strategies were discussed that can be an effective solution in the future for managing complicated diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: To compare COVID-19-associated pulmonary mucormycosis (CAPM) with COVID-19-associated rhino-orbital mucormycosis (CAROM), ascertain factors associated with CAPM among patients with COVID-19, and identify factors associated with 12-week mortality in CAPM., Methods: We performed a retrospective multicentre cohort study. All study participants had COVID-19. We enrolled CAPM, CAROM, and COVID-19 subjects without mucormycosis (controls; age-matched). We collected information on demography, predisposing factors, and details of COVID-19 illness. Univariable analysis was used to compare CAPM and CAROM. We used multivariable logistic regression to evaluate factors associated with CAPM (with hypoxemia during COVID-19 as the primary exposure) and at 12-week mortality., Results: We included 1724 cases (CAPM [n = 122], CAROM [n = 1602]) and 3911 controls. Male sex, renal transplantation, multimorbidity, neutrophil-lymphocyte ratio, intensive care admission, and cumulative glucocorticoid dose for COVID-19 were significantly higher in CAPM than in CAROM. On multivariable analysis, COVID-19-related hypoxemia (aOR, 2.384; 95% CI, 1.209-4.700), male sex, rural residence, diabetes mellitus, serum C-reactive protein, glucocorticoid, and zinc use during COVID-19 were independently associated with CAPM. CAPM reported a higher 12-week mortality than CAROM (56 of the 107 [52.3%] vs. 413 of the 1356 [30.5%]; p = 0.0001). Hypoxemia during COVID-19 (aOR [95% CI], 3.70 [1.34-10.25]) and Aspergillus co-infection (aOR [95% CI], 5.40 [1.23-23.64]) were independently associated with mortality in CAPM, whereas surgery was associated with better survival., Discussion: CAPM is a distinct entity with a higher mortality than CAROM. Hypoxemia during COVID-19 illness is associated with CAPM. COVID-19 hypoxemia and Aspergillus co-infection were associated with higher mortality in CAPM., (Copyright © 2023 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Croton tiglium Linn. (CT) which is commonly called Jaypal is used in Ayurvedic preparations like Ichhabhedi Ras, Asvakancuki Rasa. Due to its toxic contents, seeds of Croton tiglium are purified before use, by the process mentioned in classical Ayurvedic texts called Shodhana meaning purification., Objectives: The objective of the present study is to study the impact of Ayurvedic Purification process on cytotoxicity and genotoxicity of Croton tiglium Linn., Materials and Methods: Croton tiglium Linn. Seeds were processed for Shodhana by soaking in water, heating with milk (Snehan) and later grinding in Lemon Juice (Bhavana). Aqueous and Hydroalcoholic extracts were prepared before and after purification i.e. Shodhana. Cytotoxicity of the Croton tiglium was studied against Chinese Hamster Ovary cell line by MTT assay. Ames test was performed to study the mutagenicity of the extracts in Salmonella typhi TA 98, 100 and 102 strains. Phytoconstituents were studied by using LCMS analysis., Results: The results indicated decrease in cytotoxic concentration (IC 50 ) of Croton tiglium seeds after purificationa from 3.03 mg/mL to 0.99 mg/mL in aqueous extract and 18.56 mg/mL to 5.45 mg/mL. Genotoxicity study by Ames test indicated Croton tiglium Linn. Croton tiglium Linn. Seeds are non-genotoxic in strains like S. typhi, TA 98, 100 and 102. There was change in Phytochemical profile before and after shodhana., Conclusion: Although both the concentrations are practically non-toxic, the decrease in cytotoxic concentration indicates Purification process as described in classical ayurvedic texts i.e. Shodhana has definitely increased the potency of the seeds of Croton tiglium Linn., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Phosphoinositide 3-kinase (PI3K) pathway mediates key signaling events downstream to B-cell receptor (BCR) for survival of mature B-cells, and overexpression or overactivation of PI3Kδ is crucial for B-cell malignancies such as diffuse large B-cell lymphoma (DLBCL). Small molecule PI3Kδγ inhibitors, with a known potential to reduce activated B-cell (ABC)-DLBCL transformation, form an important class of therapeutics approved for follicular lymphoma (FL), chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL). In this study, we describe discovery of a potent, selective and efficacious dual PI3Kδγ inhibitor, LL-00084282, having a differentiated efficacy profile in human ABC- and germinal center B-cell (GCB)-DLBCL cell lines. LL-00084282 displayed high potency and superior PI3Kδγ engagement with excellent selectivity over other PI3K isoforms at both IC 50/90 concentrations in biochemical and cell-based assays. In contrast to selective PI3Kδ inhibitors, LL-00084282 showed superior and potent anticancer activity in both ABC- and GCB-DLBCL cell lines. LL-00084282 demonstrated in-vivo efficacy in OCI-Ly10 and SU-DHL-6 xenografts with good tolerability. Furthermore, LL-00084282 inhibited pro-inflammatory cytokine secretion and reduced basophil activation in human PBMCs, showing potential implications in immunoinflammatory conditions. Good pharmacokinetic properties in higher species and desirable efficacy profile highlights potential of this novel PI3Kδγ inhibitor for further clinical evaluation in DLBCL patients., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Manojkumar Ramprasad SHUKLA has patent #WO2016001855A1 issued to LUPIN LIMITED., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Outbreak of Corona Virus Disease in late 2019 (COVID-19) has become a pandemic global Public health emergency. Since there is no approved anti-viral drug or vaccine declared for the disease and investigating existing drugs against the COVID-19., Objective: AYUSH-64 is an Ayurvedic formulation, developed and patented by Central Council of Research in Ayurvedic Sciences, India, has been in clinical use as anti-malarial, anti-inflammatory, anti-pyretic drug for few decades. Thus, the present study was undertaken to evaluate AYUSH-64 compounds available in this drug against Severe Acute Respiratory Syndrome-Corona Virus (SARS-CoV-2) Main Protease (M pro ; PDB ID: 6LU7) via in silico techniques., Materials and Methods: Different molecular docking software's of Discovery studio and Auto Dock Vina were used for drugs from selected AYUSH-64 compounds against SARS-CoV-2. We also conducted 100 ns period of molecular dynamics simulations with Desmond and further MM/GBSA for the best complex of AYUSH-64 with M pro of SARS-CoV-2., Results: Among 36 compounds of four ingredients of AYUSH-64 screened, 35 observed to exhibits good binding energies than the published positive co-crystal compound of N3 pepetide. The best affinity and interactions of Akuammicine N-Oxide (from Alstonia scholaris ) towards the M pro with binding energy (AutoDock Vina) of -8.4 kcal/mol and Discovery studio of Libdock score of 147.92 kcal/mol. Further, molecular dynamics simulations with MM-GBSA were also performed for M pro - Akuammicine N-Oxide docked complex to identify the stability, specific interaction between the enzyme and the ligand. Akuammicine N-Oxide is strongly formed h-bonds with crucial M pro residues, Cys145, and His164., Conclusion: The results provide lead that, the presence of M pro - Akuammicine N-Oxide with highest M pro binding energy along with other 34 chemical compounds having similar activity as part of AYUSH-64 make it a suitable candidate for repurposing to management of COVID-19 by further validating through experimental, clinical studies., Competing Interests: None., (© 2021 The Authors.)

Aim: This in vitro study intend to compare the cleaning effectiveness of Protaper universal sequence with reciprocating F2 Protaper and single rotary file One shape., Materials and Method: 30 extracted human 1st mandibular molars were chosen for the analysis. Three NiTi file systems were used for mechanical preparation, ProTaper full sequence in rotary motion, single F2 Protaper file used in reciprocating motion, and One shape single file used in a circular motion. Irrigation was carried out after each instrument use using 5 ml of 5% NaOCl followed by normal saline. The root canal surface was evaluated at three different areas (coronal, middle and apical thirds) using Scanning Electron Microscopy. Debris and the Smear layer were evaluated. Data were analyzed statistically using the Friedman test and Kruskal-Wallis test (p ≤ 0.05)., Results: A statistically significant difference (p ≤ 0.05) was observed in the debris score of the Protaper universal group when the 3 thirds of the root were compared. Intergroup comparisons confirmed a statistically significant difference at the coronal and apical third of the roots when debris scores were evaluated. Intragroup comparison for the smear layer demonstrated a statistically significant difference (p ≤ 0.05) at all the 3 levels of the radicular canal for the 3 groups studied. Intergroup comparisons revealed a statistically significant difference (p ≤ 0.05) in the middle and apical 1/3rd when the smear layer was evaluated., Conclusion: The Protaper full sequence group provided better results than Single F2 ProTaper and One shape groups when debris and smear layer removal was investigated., Competing Interests: The authors declare that they have no Conflict of Interest., (© 2020 Craniofacial Research Foundation. Published by Elsevier B.V. All rights reserved.)

Adaptive cellular stress response confers stress tolerance against inflammatory and metabolic disorders. In response to metabolic stress, the key mediator of cellular adaptation and tolerance is a class of molecules called the molecular chaperones (MCs). MCs are highly conserved molecules that play critical role in maintaining protein stability and functionality. Hormesis in this context is a unique adaptation mechanism where a low dose of a stressor (which is toxic at high dose) confers a stress-resistant adaptive cellular phenotype. Hormesis can be observed at different level of biological organization at various measurable endpoints. The MCs are believed to play a key role in adaptation during hormesis. Several phytochemicals are known for their hormetic response and are called phytochemical hormetins. The role of phytochemical-mediated hormesis on the adaptive cellular processes is proposed as a potential therapeutic approach to target inflammation associated with metabolic syndrome. However, the screening of phytochemical hormetins would require a paradigm shift in the methods currently used in drug discovery., (Copyright © 2020. Published by Elsevier Ltd.)

Lysozyme (LYZ) is a model protein frequently employed to study interaction with drugs and to understand the crystallization process of protein due to its small size and rapid crystallization behavior. Studies related to drug interaction and complexation with proteins will be significantly benefited if a suitable drug-lysozyme crystal is available. This can further aid in the understanding of the mechanism of nucleation, growth and the formation of drug-lysozyme complex. In the present study, amlodipine (AMLD) complexation with LYZ has been monitored, along with its effect on lysozyme crystallization. Different spectroscopic methods have been employed to monitor the nature of complexation, binding mode and changes in helix after interaction with AMLD. The absorbance and fluorescence spectroscopic measurement indicated the probability of a ground state complex between LYZ and AMLD. Further, the temperature dependent fluorescence studies showed an increase in binding constant with temperature, suggesting the static quenching mechanism involved in complex formation due to hydrophobic interactions. CD, FTIR, DLS and DSC techniques confirm the probability of changes in the tertiary structure of protein. Molecular docking was applied to investigate the interaction of amino acid residues of LYZ with AMLD. It was found that the complex formation is spontaneous and the ΔG value obtained (-21. 76 kJ/mol) very well matched with temperature dependent fluorescence study (-24.91 kJ/mol). Crystallization of LYZ was performed with different concentration ranges of AMLD to get a clear picture of its interference on the process. The time required for crystallization of AMLD-LYZ complex and the observed structure of crystal indicates that AMLD influences lysozyme crystallization process by changing the nature of nucleation and rate of crystal growth., (Copyright © 2019 Elsevier B.V. All rights reserved.)

HIV-1 protease inhibitors are effective in HIV/AIDS therapy, although drug resistance is a severe problem. This study examines the effects of four investigational inhibitors against HIV-1 protease with drug resistant mutations of V32I, I47V and V82I (PR Tri ) that model the inhibitor-binding site of HIV-2 protease. These inhibitors contain diverse chemical modifications on the darunavir scaffold and form new interactions with wild type protease, however, the measured inhibition constants for PR Tri mutant range from 17 to 40 nM or significantly worse than picomolar values reported for wild type enzyme. The X-ray crystal structure of PR Tri mutant in complex with inhibitor 1 at 1.5 Å resolution shows minor changes in interactions with inhibitor compared with the corresponding wild type PR complex. Instead, the basic amine at P2 of inhibitor together with mutation V82I induces two alternate conformations for the side chain of Arg8 with new interactions with inhibitor and Leu10. Hence, inhibition is influenced by small coordinated changes in hydrophobic interactions., (Copyright © 2019 Elsevier Inc. All rights reserved.)

A huge surge of research is being conducted on combination therapy with anticancer compounds formulated in the form of nanoparticles (NPs). Numerous advantages like dose minimalization and synergism, reversal of multi drug resistance (MDRs), enhanced efficacy have emerged with nanoencapsulation of chemotherapeutic agents with chemo-sensitizing agent like curcumin. Within last couple of years various nano-sized formulations have been designed and tested both in vitro with cell lines for different types of cancers and in vivo with cancer types and drug resistance models. Despite the combinatorial models being advanced, translation to human trials has not been as smooth as one would have hoped, with as few as twenty ongoing clinical trials with curcumin combination, with less than 1/10th being nano-particulate formulations. Mass production of nano-formulation based on their physico-chemical and pharmacokinetics deficits poses as major hurdle up the ladder. Combination of these nano-sized dosage with poorly bioavailable drugs, unspecific target binding ability and naturally unstable curcumin further complicates the formulation aspects. Emphasis is now therefore being laid on altering natural forms of curcumin and usage of formulations like prodrug or coating of curcumin to overcome stability issues and focus more on enhancing the pharmaceutical and therapeutic ability of the nano-composites. Current studies and futuristic outlook in this direction are discussed in the review, which can serve as the basis for upcoming research which could boost commercial translational of improved nano-sized curcumin combination chemotherapy., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Introduction: Primary breast cancer in adolescents is extremely rare and thus is not widely studied. This study aimed to evaluate trends, characteristics, and outcomes among a cohort of adolescents with breast cancer., Patients and Methods: A total of 657,712 female patients with breast cancer from Surveillance Epidemiology and End Results (SEER) database (1973-2009) were analyzed, and 91 adolescents were identified. Three age groups (under 20 years, 20-50 years or premenopausal, and > 50 years or postmenopausal) were compared for tumor size, stage, receptor status, and outcomes. Categorical data were compared by chi-square (Fisher) test and continuous data with Student's t test., Results: Median age was 19 years (range, 10-20 years). A total of 52.7% (n = 48) and 5.5% (n = 5) of patients presented with invasive and in-situ cancers, respectively, and 37.3% (n = 34) with sarcomas. Median tumor size of invasive cancers was 3.2 cm (range, 0.1-12.5 cm). Sixty percent of patients presented with regional disease, and the majority (28%) of those tested were receptor negative. Mortality rates in adolescents were higher than pre- and postmenopausal patients in localized and regional stage. Overall median survival was 106 months., Conclusion: Although rare, breast cancer does occur in adolescent girls and must be considered in differential of breast masses in females under 20, especially with strong breast cancer family history. Prognosis maybe worse than in older patients; however, the sample size is small. Delay in diagnosis, aggressive tumor biology, and negative receptor status may affect prognosis. Routine breast examination in high-risk older adolescents may permit early identification and avoid delay in diagnosis and treatment., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: We have previously reported inactivation of p53 in 46% of Indian patients with oral cancer. Survivin, a p53 target gene and an inhibitor of apoptosis protein (IAP), is overexpressed in several cancers, including oral cancers. Studies assessing the role of survivin and its splice variants in oral cancers are, however, rare., Materials and Methods: The expression of 6 survivin isoforms in 4 oral cancer cell lines (AW8507, AW13516, UPCI-SCC040, UPCI-SCC029 B), a dysplastic oral cell line (DOK), 75 paired oral tumor and adjacent normal tissues, and 12 normal oral tissue samples from healthy individuals was analyzed by real-time PCR. The expression was correlated with clinicopathologic parameters, which included age, sex, tumor-node-metastasis (TNM) staging, tobacco and/or alcohol consumption, site, and differentiation status of tumor., Results: This is the first study to find overexpression of the 6 characterized survivin isoforms in oral cancers compared with normal tissues (P < .05). Additionally, a significant (P < .05) correlation among the fold changes of all 6 survivin isoforms was observed. Survivin wild type (wt) was the predominantly expressed isoform in oral cell lines and tumor tissues versus normal tissues (P < .05). Among the minor isoforms, survivin ΔEx3 and survivin 2 B were dominantly expressed, whereas survivin 2 α and survivin 3 α overexpression was found for the first time. Further high survivin 3 B expression exhibited a significant association (P < .05) with poorly differentiated tumors. Interestingly the combined expression of the antiapoptotic survivin isoforms, survivin wt, survivin ΔEx3, and survivin 3 B, exhibited a significant association with TNM staging of the tumor., Conclusions: Our studies thus indicate that oral cancers overexpress the antiapoptotic survivin variants, which exhibit an association with advanced tumor stage, implying a role for these variants in oral tumorigenesis., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Serovars of Salmonella enterica, namely Typhi and Typhimurium, reportedly, are the bacterial pathogens causing systemic infections like gastroenteritis and typhoid fever. To elucidate the role and importance in such infection, the proteins of the Type III secretion system of Salmonella pathogenicity islands and two component signal transduction systems, have been mainly focused. However, the most indispensable of these virulent ones and their hierarchical role has not yet been studied extensively., Results: We have adopted a theoretical approach to build an interactome comprising the proteins from the Salmonella pathogeneicity islands (SPI) and two component signal transduction systems. This interactome was then analyzed by using network parameters like centrality and k-core measures. An initial step to capture the fingerprint of the core network resulted in a set of proteins which are involved in the process of invasion and colonization, thereby becoming more important in the process of infection. These proteins pertained to the Inv, Org, Prg, Sip, Spa, Ssa and Sse operons along with chaperone protein SicA. Amongst them, SicA was figured out to be the most indispensable protein from different network parametric analyses. Subsequently, the gene expression levels of all these theoretically identified important proteins were confirmed by microarray data analysis. Finally, we have proposed a hierarchy of the proteins involved in the total infection process. This theoretical approach is the first of its kind to figure out potential virulence determinants encoded by SPI for therapeutic targets for enteric infection., Conclusions: A set of responsible virulent proteins was identified and the expression level of their genes was validated by using independent, published microarray data. The result was a targeted set of proteins that could serve as sensitive predictors and form the foundation for a series of trials in the wet-lab setting. Understanding these regulatory and virulent proteins would provide insight into conditions which are encountered by this intracellular enteric pathogen during the course of infection. This would further contribute in identifying novel targets for antimicrobial agents., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Cancer metastasis is a multi-step process in which tumor cells gain the ability to invade beyond the primary tumor and colonize distant sites. The mechanisms regulating the metastatic process confer changes to cell adhesion receptors including the integrin family of receptors. Our group previously discovered that the α6 integrin (ITGA6/CD49f) is post translationally modified by urokinase plasminogen activator (uPA) and its receptor, urokinase plasminogen activator receptor (uPAR), to form the variant ITGA6p. This variant of ITGA6 is a cleaved form of the receptor that lacks the ligand-binding domain. Although it is established that the uPA/uPAR axis drives ITGA6 cleavage, the mechanisms regulating cleavage have not been defined. Intracellular integrin dependent "inside-out" signaling is a major regulator of integrin function and the uPA/uPAR axis. We hypothesized that intracellular signaling molecules play a role in formation of ITGA6p to promote cell migration during cancer metastasis. In order to test our hypothesis, DU145 and PC3B1 prostate cancer and MDA-MB-231 breast cancer cell lines were treated with small interfering RNA targeting actin and the intracellular signaling regulators focal adhesion kinase (FAK), integrin linked kinase (ILK), and paxillin. The results demonstrated that inhibition of actin, FAK, and ILK expression resulted in significantly increased uPAR expression and ITGA6p production. Inhibition of actin increased ITGA6p, although inhibition of paxillin did not affect ITGA6p formation. Taken together, these results suggest that FAK and ILK dependent "inside-out" signaling, and actin dynamics regulate extracellular production of ITGA6p and the aggressive phenotype., (Copyright © 2014 Elsevier Inc. All rights reserved.)

At our laboratory, we recently observed cell cycle and apoptosis-related proteins Myeloid Cell Leukemia-1 (Mcl-1) and Proliferating Cell Nuclear Antigen (PCNA) to be altered in oral tumours/cell lines. The present study aimed to evaluate the above proteins for predicting response and outcome in oral cancer patients treated with definitive radiotherapy. Pre-treatment oral cancer biopsy samples from 39 patients were examined for Mcl-1 and PCNA proteins using immunohistochemistry and correlated with clinico-pathological variables using disease-free survival (DFS) as the primary endpoint. We observed high expression of Mcl-1 in older versus younger patients (p=0.013) and in tobacco chewers+/-alcohol versus smokers+/-alcohol (p=0.037); and PCNA in node-positive versus node-negative tumours (p=0.037). On univariate analysis, high PCNA (p=0.007), Mcl-1 (p=0.050), node positivity (p=0.040) and co-expression of PCNA and Mcl-1 (p=0.008), had a significant impact on DFS. On multivariate analysis, low PCNA/Mcl-1 (p=0.006) co-expressing tumours were associated with improved DFS. Thus our study suggests that in patients undergoing primary radiotherapy, PCNA could be of potential predictive value to identify patients with risk of nodal metastases and in combination with Mcl-1 may have potential prognostic value to differentiate patients with poor DFS. These markers may be used for future trial patients requiring radiotherapy for their treatment., (Copyright 2010 Elsevier Ltd. All rights reserved.)