A comparative survey between cascade correlation neural network (CCNN) and feedforward neural network (FFNN) machine learning models for forecasting suspended sediment concentration.

Suspended sediment concentration prediction is critical for the design of reservoirs, dams, rivers ecosystems, various operations of aquatic resource structure, environmental safety, and water management. In this study, two different machine models, namely the cascade correlation neural network (CCNN) and feedforward neural network (FFNN) were applied to predict daily-suspended sediment concentration (SSC) at Simga and Jondhara stations in Sheonath basin, India. Daily-suspended sediment concentration and discharge data from 2010 to 2015 were collected and used to develop the model to predict suspended sediment concentration. The developed models were evaluated using statistical indices like Nash and Sutcliffe efficiency coefficient (NES), root mean square error (RMSE), Willmott's index of agreement (WI), and Legates-McCabe's index (LM), supplemented by a scatter plot, density plots, histograms and Taylor diagram for graphical representation. The developed model was evaluated and compared with CCNN and FFNN. Nine input combinations were explored using different lag-times for discharge (Qt-n) and suspended sediment concentration (St-n) as input variables, with the current suspended sediment concentration as the desired output, to develop CCNN and FFNN models. The CCNN4 model with 4 lagged inputs (St-1, St-2, St-3, St-4) outperformed the other developed models with the lowest RMSE = 95.02 mg/l and the highest NES = 0.0.662, WI = 0.890 and LM = 0.668 for the Jondhara Station while the same CCNN4 model secure as the best with the lowest RMSE = 53.71 mg/l and the highest NES = 0.785, WI = 0.936 and LM = 0.788 for the Simga Station. The result shows the CCNN model was better than the FFNN model for predicting daily-suspended sediment at both stations in the Sheonath basin, India. Overall, CCNN showed better forecasting potential for suspended sediment concentration compared to FFNN at both stations, demonstrating their applicability for hydrological forecasting with complex relationships.

The Labyrinthine Journey: Unveiling Obstacles in addressing Mental Health Challenges in Prisons and its Confluence with Medico-Legal and Pharmacological Perspectives.

This paper delves into the intricate realm of mental health issues within prisons including other correctional facilities, the intersectionality with legal and medical aspects, and the potential of pharmacology as a viable treatment modality. The prevalence and diverse array of mental disorders among incarcerated individuals are thoroughly examined, underscoring the imperative for all-encompassing interventions. The legal structure, hurdles encountered in delivering mental healthcare, and the indispensability of interdisciplinary cooperation are scrutinized. Furthermore, the effectiveness and moral implications of pharmaceutical interventions in correctional environments are deliberated upon. Conclusive suggestions are put forth to enhance mental healthcare provisions in prisons. The research paper endeavors to penetrate the labyrinthine complexities of mental health predicaments within correctional institutions, with a specific emphasis on the convergence of medico-legal facets and the plausible impact of pharmacological interventions. The study strives to elucidate the intricate nature of mental health challenges among incarcerated populations, considering the intricate interplay of socio-cultural, environmental, and psychological factors that contribute to their pervasiveness. By delving into these interconnected dimensions, the research aims to unlock prospective remedies capable of efficaciously meeting the mental health requisites of incarcerated individuals.

Fish cell line: depositories, web resources and future applications.

Cell lines are important bioresources to study the key biological processes in the areas like virology, pathology, immunology, toxicology, biotechnology, endocrinology and developmental biology. Cell lines developed from fish organs are utilized as a model in vitro system in disease surveillance programs, pharmacology, drug screening and resolving cases of metabolic abnormalities. During last decade, there were consistent efforts made globally to develop new fish cell lines from different organs like brain, eye muscles, fin, gill, heart, kidney, liver, skin, spleen, swim bladder, testes, vertebra etc. This increased use and development of cell lines necessitated the establishment of cell line depositories to store/preserve them and assure their availability to the researchers. These depositories are a source of authenticated and characterized cell lines with set protocols for material transfer agreements, maintenance and shipping as well as logistics enabling cellular research. Hence, it is important to cryopreserve and maintain cell lines in depositories and make them available to the research community. The present article reviews the current status of the fish cell lines available in different depositories across the world, along with the prominent role of cell lines in conservation of life on land or below water. Supplementary Information: The online version contains supplementary material available at 10.1007/s10616-023-00601-2.

Influence of Select Dietary Trace Minerals and their Levels on Growth Performance, Nutrient Utilization and Minerals Balance in Male Goats.

A study was conducted on eighteen male goats to evaluate the effect of incremental levels of select dietary trace minerals on growth performance, nutrient utilization and minerals balance. Animals (16.65 ± 0.53 kg average BW) were randomly divided into three groups and fed a basal diet to meet the requirement of all the nutrients except select trace minerals for 60 days. Groups were T1 (0.204 ppm Se, 35.29 ppm Zn, 7.37 ppm Cu, 39.79 ppm Mn), T2 (0.504 ppm Se, 55.29 ppm Zn, 17.37 ppm Cu, 59.79 ppm Mn), and T3 (0.804 ppm Se, 75.29 ppm Zn, 27.37 ppm Cu, 79.79 ppm Mn). Daily dry matter intake (DMI) (% BW) was lower (P < 0.05) in T3 as compared to other groups however, average daily gain (ADG) in body weight (P = 0.113) and feed: gain ratio (P = 0.102) showed subtle improvement in T2 and T3 groups. Feeding of higher levels of select trace minerals did not affect the intake and digestibility of nutrients, or plane of nutrition, however, the digestibility of non-fiber carbohydrates (NFC) increased (P = 0.004) in T2 and T3 groups than T1. The balance of N, Ca, P and Cu did not differ among the groups but balance of Zn, Mn and Se increased in T2 and T3 groups than T1 group. It is concluded that feeding higher levels of Zn (75.29 ppm), Cu (27.37 ppm), Mn (79.79 ppm) and Se (0.804 ppm) in combination, improved NFC digestibility, retention of Zn, Mn and Se and had subtle beneficial effects on the growth performance of male goats.

Optimal Cut-Off Values for Body Mass Index and Fat Mass Index Based on Age in Physically Active Males Using Receiver Operating Characteristic Curve.

This study aims to redefine obesity cut-off points for body mass index (BMI) and fat mass index (FMI) according to the different age groups of physically active males. Healthy physically active volunteers (N = 1442) aged 18-57 years (y), with a mean BMI = 22.7 ± 2.8 kg/m2, and mean FMI = 4.3 ± 1.7 kg/m2 were recruited from various fitness centers. BMI was calculated and individuals were categorized according to the Asia-Pacific BMI criterion of ≤22.9 kg/m2 and the previous WHO-guided BMI criterion of ≤24.9 kg/m2. FMI was also calculated for the study participants with a cut-off of 6.6 kg/m2. Redefining of BMI and FMI cut-off values was carried out based on different age groups categorized with a difference of 10 y and 5 y using the receiver operating characteristic (ROC) curve and Youden's index. For the entire study population, BMI redefined cut-off points for overweight and obesity were 23.7 kg/m2 and 24.5 kg/m2, respectively, while FMI redefined cut-off points for overweight and obesity were 4.6 kg/m2 and 5.7 kg/m2, respectively. With 10 y of age group difference, a constant BMI and FMI values were observed, while with 5 y of age group difference, a constant increase in the BMI cut-offs was observed as the age group increased, i.e., from 23.3 kg/m2 in 20-24 y to 26.6 kg/m2 in ≥45 y and a similar trend was seen in FMI cut-offs. To conclude, our study suggests that age-dependent BMI and FMI cut-off points may provide appropriate measurements for physically active males as the age group increases.

Development and validation of a reliable rabbit model of limbal stem cell deficiency by mechanical debridement using an ophthalmic burr.

A simple and reproducible method is necessary to generate reliable animal models of limbal stem cell deficiency (LSCD) for assessing the safety and efficacy of new therapeutic modalities. This study aimed to develop and validate a rabbit model of LSCD through mechanical injury. The corneal and limbal epithelium of New Zealand White rabbits (n = 18) were mechanically debrided using an ophthalmic burr (Algerbrush II) with a 1.0-mm rotating head after 360° conjunctival peritomy. The debrided eyes were serially evaluated for changes in corneal opacity, neo-vascularization, epithelial defect and corneal thickness using clinical photography, slit lamp imaging, fluorescein staining, and anterior segment optical coherence tomography scanning (AS-OCT). Following this, an assessment of histopathology and phenotypic marker expression of the excised corneas was conducted. The experimental eyes were grouped as mild (n = 4), moderate (n = 10), and severe (n = 4) based on the grade of LSCD. The moderate group exhibited abnormal epithelium, cellular infiltration in the stroma, and vascularization in the central, peripheral, and limbal regions of the cornea. The severe group demonstrated central epithelial edema, peripheral epithelial thinning with sparse goblet cell population, extensive cellular infiltration in the stroma, and dense vascularization in the limbal region of the cornea. A significant decrease in the expression of K12 and p63 (p < 0.0001) was observed, indicating the loss of corneal epithelium and limbal epithelial stem cells in the LSCD cornea. This study demonstrates that the Alger brush-induced mechanical debridement model provides a reliable model of LSCD with comprehensive clinic-pathological features and that is well suited for evaluating novel therapeutic and regenerative approaches.

Shear bond strengths of bur or Er:YAG laser prepared dentine to composite resin with or without low-level laser conditioning: an in vitro study.

This study aims to compare the different modes of cavity preparation while evaluating the effect of low-level laser therapy (LLLT) on dentine before bonding in terms of shear bond strength between composite resin and dentine. Fifty human molar teeth were mounted on acrylic blocks and dentine specimen were prepared after which they were randomized into four equal groups. Cavity preparation mode differed in respective groups. After etching, bonding; composite resin was placed and polymerized on the prepared dentine surfaces. The specimens were kept in an environment simulating oral cavity and then shear tested in a universal testing machine. The failure surfaces of the specimen teeth were subjected to SEM micrographic evaluation. The cavity prepared with diamond abrasive points had a higher shearing load at failure that was statistically significantly different from the ones prepared with laser. That with diamond abrasive points followed by LLLT of the cavity surface with Nd:YAG laser had a higher bond strength than the ones prepared with just Er:YAG laser and there was no statistically significant difference between these and the ones prepared with diamond abrasive points alone. SEM analysis of the failure mode in bur-cut dentine showed the presence of a hybrid layer at the interface. Surface conditioning of the same with Nd:YAG laser before etching suggested a recrystallisation of dentine due to the heat produced. Cavity preparation with Er:YAG laser leads to reduced shear bond strength to adhesive restorative materials when compared with that using burs and high-speed handpiece.

Comparison of traditional essay questions versus case based modified essay questions in biochemistry.

Adult learning involves the analysis and synthesis of knowledge to become competent, which cannot be assessed only by traditional assessment tool and didactic learning methods. Stimulation of higher domains of cognitive learning needs to be inculcated to reach a better understanding of the subject rather than traditional assessment tools that relies primarily on rote learning. So, there is need for an alternative assessment tool. Hence, we conducted a study where we used case-based examination methodology. This study was conducted on 226 Ist year MBBS students in Maulana Azad Medical College, New Delhi (India). Based on their compiled internal assessment marks according to monthly formative assessment, students were categorized into 3 groups (I: 0-7; II: 8-14; III: 15-20) marks out of 20 marks respectively. Two sets of question papers were set by three examiners, on the same topics carrying 50 marks each. The first set was based on traditional assessment tool (Paper-A) with recall questions and second set on case-based assessment method (Paper-B). Out of 226 students, 146 were males and 80 were females. For all groups, marks (mean ± SD) in Paper B were found to be higher (18.40 ± 4.29, 30.01 ± 4.12, and 40.33 ± 1.15) as compared to paper A (10.88 ± 4.34, 21.96 ± 7.34, and 31.50 ± 6.94) respectively. However, we found that there was significant (p < 0.001) difference in group I & II, whereas with group III, difference was found to be insignificant. Hence, we concluded that students performed better in case-based assessment rather than traditional method due to their direct involvement. Thus, for better memory and deeper learning the subjects can be assessed by case-based assessment method.

Utilization of Chemometric-Aided UV Spectrophotometric Methods for Concurrent Assessment of Emtricitabine, Tenofovir Disoproxil Fumarate, Elvitegravir, and Cobicistat in Tablet Formulation.

BACKGROUND: Emtricitabine (ETC), tenofovir disoproxil fumarate (TNF), elvitegravir (EVG), and cobicistat (CBS) are antiviral drugs used to treat human immunodeficiency virus (HIV) infections. OBJECTIVE: To develop chemometric-aided UV spectrophotometric methods for concurrent estimation of the aforementioned drugs used to treat HIV. This method can be used to reduce modification of the calibration model by assessing the absorbance at various points in the zero-order spectra within the selected wavelength range. Additionally, it eliminates interfering signals and provides sufficient resolution in multi-component systems. METHODS: Two chemometric-assisted UV spectrophotometric methods, namely, partial least-squares (PLS) and principal component regression (PCR) models, were established for the concurrent assessment of EVG, CBS, TNF, and ETC in tablet formulations. The proposed methods were applied to decrease complexity of overlapped spectra and to achieve maximum sensitivity and the lowest error. These approaches were performed in accordance with International Council on Harmonization (ICH) criteria and compared to the reported HPLC method. RESULTS: The proposed methods were used to assess EVG, CBS, TNF, and ETC in the ranges of 5-30, 5-30 , 5-50, and 5-50 µg/mL, respectively, with an excellent correlation coefficient (r2 ≥ 0.998). The accuracy and precision results were found to be within the acceptable limits. No statistical difference was observed between the proposed and reported studies. CONCLUSION: The chemometric-aided UV spectrophotometric approaches could be considered as alternatives to chromatographic procedures in the pharmaceutical industry for routine analysis and testing of readily accessible commercial formulations. HIGHLIGHTS: Novel chemometric-assisted UV spectrophotometric techniques were developed for assessment of multicomponent antiviral combinations in single-tablet formulations. The proposed methods were performed without using harmful solvents, tedious preparation, or expensive instruments. The proposed methods were compared statistically with a reported HPLC method. Assessment of EVG, CBS, TNF, and ETC was performed without interference from excipients in their multicomponent formulations.

Erratum: [Corrigendum] Differential regulation of mitochondrial complex I and oxidative stress based on metastatic potential of colorectal cancer cells.

[This corrects the article DOI: 10.3892/ol.2020.12176.].

Modulatory role of BV6 and chloroquine on the regulation of apoptosis and autophagy in non-small cell lung cancer cells.

Aims: Non-small cell lung cancer (NSCLC) is one of the aggressive tumors mostly diagnosed in the advanced stage. Therapeutic failure and drug resistance pose a major problem in NSCLC treatment primarily due to alterations in autophagy and loss of apoptosis. Therefore, the present study aimed to investigate the importance of the second mitochondria-derived activator of caspase mimetic BV6 and autophagy inhibitor chloroquine (CQ) on the regulation of apoptosis and autophagy, respectively. Subjects and Methods: Study was conducted on NCI-H23 and NCI-H522 cell lines to evaluate the effect of BV6 and CQ on the transcription and translation level of LC3-II, caspase-3, and caspase-9 genes by quantitative real-time-polymerase chain reaction and western blotting techniques. Results: In NCI-H23 cell line, BV6 and CQ treatments showed increased mRNA and protein expression of caspase-3, and caspase-9 compared to its untreated counterpart. BV6 and CQ treatments also caused downregulation of LC3-II protein expression compared to its counterpart. In NCI-H522 cell line, BV6 treatment showed a significantly increased expression of caspase-3 and caspase-9 mRNA and protein expression levels whereas BV6 treatment downregulated the expression level of LC3-II protein. A similar pattern was also observed in CQ treatment when compared with the respective controls. Both BV6 and CQ modulated in vitro expression of caspases and LC3-II which have critical regulatory roles in apoptosis and autophagy, respectively. Conclusions: Our findings suggest that BV6 and CQ could be promising candidates in NSCLC treatment and there is a need to explore them in vivo and in clinical applications.

Inhibition of miR-214 expression by small molecules alleviates head and neck cancer metastasis by targeting ALCAM/TFAP2 signaling.

Predominantly, head and neck cancer (HNC) is considered a regional disease and develops in the nasal cavity, oral cavity, tongue, pharynx, and larynx. In the advanced stage, the HNC spread into distant organs. By the time head and neck cancer diagnosed, the estimated metastasis is occurred in 10-40% cases. The most important vital organs affected by distant metastasis are the lungs, bones, and liver. Despite several advancements in chemotherapies, no significant changes are observed as 5-year survival rate remains the same. Therefore, it is crucial to decipher molecular mechanisms contributing to the metastatic dissemination of head and neck cancer. Here, we tested a novel ALCAM/TFAP2 signaling by targeting multidisciplinary miR-214 expression in head and cancer cells. Our results revealed that HNC cell lines (CAL27, SCC-9, SCC-4, and SCC-25) exhibit higher expression of miR-214 compared with normal human bronchial epithelial (NHBE) cells. Higher expression of miR-214 drives the invasive potential of these cell lines. Down-regulation of miR-214 in CAL27 and SCC-9 cells either using an anti-miR-214 inhibitor (50nM) or a small molecule of green tea (EGCG) inhibited cell invasion. Treating CAL27 and SCC-9 cells with EGCG also reduces ALCAM expression, a key activated leukocyte cell adhesion molecule, potentially blocking mesenchymal phenotype. Dietary administration of EGCG significantly inhibits distant metastasis of SCC-9 cells into the lungs, liver, and kidneys. Our results also demonstrate that the reduction of miR-214 expression influences in vitro cell movement and extravasation, as evident by reduced CD31 expression, a neovascularization marker. Together, these studies suggest that identifying bioactive molecules that can inhibit distant metastasis regulated by the miRNAs may provide potent interventional approaches and a better understanding of the complex functions of miRNAs and their therapeutic targets for clinical application.

Optimization and evaluation of tear protein elution from Schirmer's strips in dry eye disease.

PURPOSE: Extraction of tear protein from Schirmer's strip is a prerequisite for the proper identification and screening of biomarkers in dry eye disease. The study compares different methods of extraction of tear proteins from the Schirmer's strip. METHODS: Reflex tear was collected from healthy controls (HC; n = 12), Stevens-Johnson syndrome (SJS; n = 3) and dry eye disease (DED; n = 3) patients using capillary tube. This tear was used to measure the volume absorbed by Schirmer's strip per microliter. Different buffers (6) were used to compare the protein yield from the Schirmer's strip in four different conditions. The tear proteins extracted using the highest protein yield buffer were analyzed by mass spectrometry. RESULTS: A linear relationship between the tear volume and wetting length was observed (r = 0.0.997, n = 6). The highest yield was observed after incubation of the Schirmer's strip in 100 mM ammonium bicarbonate (ABC) with 0.25% Nonidet P-40(NP-40) at 4°C for an hour (P < 0.00005). The in-solution digestion of tear eluted in the above condition 100 Mm ABC + 0.25% NP-40 with one-hour incubation yielded a total of 2119 proteins in HC, SJS, and DED. The unique protein observed in SJS and DED was 0.6% and 17.9%, respectively. The significantly expressed proteins are associated with innate immune response, proteolysis, wound healing, and defense response. CONCLUSION: A method for extraction of protein from Schirmer's strip was optimized for increase in protein yield from the tear sample. SJS and DED tear samples have unique protein signature. The study will aid in better design of tear protein-based experimental study.

Differentially deregulated microRNAs contribute to ultraviolet radiation-induced photocarcinogenesis through immunomodulation: An-analysis of microRNAs expression profiling.

MicroRNAs (miRNAs) are short non-coding RNA molecules (18-25 nucleotides) that regulate several fundamental biological processes. Emerging evidence has shown more than 1500 miRNAs functions in the cell cycle, proliferation, apoptosis, oxidative stress, immune response, DNA damage, and epigenetics alterations. miRNAs are bidirectionally in nature and act as a tumor suppressor and as an oncogene through crosstalk between tumor cells and immune cells. Although the roles of miRNAs in several cancers are well studied, little is known about ultraviolet B (UVB) radiation-induced skin cancer. Here, we performed a comprehensive screening of 1281 miRNAs in tumor tissues and compared their expression with normal skin. Our results demonstrate that the expression levels of 587 miRNAs were altered in tumor tissues compared to their expression in normal skin. The expression of 337 miRNAs was upregulated from 1.5-12 folds, while the expression of 250 miRNAs was downregulated up to 1.5-10 folds in tumors. Further, intraperitoneal injection of a mimic of down-regulated miR-15b (30nM) and an inhibitor of upregulated miR-133a (20nM) protect UVB-induced suppression of contact hypersensitivity (CHS) response. In conclusion, we identified a network of altered miRNAs in tumors that can serve as prognostic biomarkers and therapeutic targets to manage photocarcinogenesis effectively.

Template Entrance Channel as Possible Allosteric Inhibition and Resistance Site for Quinolines Tricyclic Derivatives in RNA Dependent RNA Polymerase of Bovine Viral Diarrhea Virus.

The development of potent non-nucleoside inhibitors (NNIs) could be an alternate strategy to combating infectious bovine viral diarrhea virus (BVDV), other than the traditional vaccination. RNA-dependent RNA polymerase (RdRp) is an essential enzyme for viral replication; therefore, it is one of the primary targets for countermeasures against infectious diseases. The reported NNIs, belonging to the classes of quinolines (2h: imidazo[4,5-g]quinolines and 5m: pyrido[2,3-g] quinoxalines), displayed activity in cell-based and enzyme-based assays. Nevertheless, the RdRp binding site and microscopic mechanistic action are still elusive, and can be explored at a molecular level. Here, we employed a varied computational arsenal, including conventional and accelerated methods, to identify quinoline compounds' most likely binding sites. Our study revealed A392 and I261 as the mutations that can render RdRp resistant against quinoline compounds. In particular, for ligand 2h, mutation of A392E is the most probable mutation. The loop L1 and linker of the fingertip is recognized as a pivotal structural determinant for the stability and escape of quinoline compounds. Overall, this work demonstrates that the quinoline inhibitors bind at the template entrance channel, which is governed by conformational dynamics of interactions with loops and linker residues, and reveals structural and mechanistic insights into inhibition phenomena, for the discovery of improved antivirals.

Epigallocatechin Gallate (EGCG), an Active Phenolic Compound of Green Tea, Inhibits Tumor Growth of Head and Neck Cancer Cells by Targeting DNA Hypermethylation.

Head and neck cancers are among the deadliest cancers, ranked sixth globally in rates of high mortality and poor patient prognoses. The prevalence of head and neck squamous cell carcinoma (HNSCC) is associated with smoking and excessive alcohol consumption. Despite several advances in diagnostic and interventional methods, the morbidity of subjects with HNSCC has remained unchanged over the last 30 years. Epigenetic alterations, such as DNA hypermethylation, are commonly associated with several cancers, including HNSCC. Thus, epigenetic changes are considered promising therapeutic targets for chemoprevention. Here, we investigated the effect of EGCG on DNA hypermethylation and the growth of HNSCC. First, we assessed the expression levels of global DNA methylation in HNSCC cells (FaDu and SCC-1) and observed enhanced methylation levels compared with normal human bronchial epithelial cells (NHBE). Treatment of EGCG to HNSCC cells significantly inhibited global DNA hypermethylation by up to 70-80% after 6 days. Inhibition of DNA hypermethylation in HNSCC cells was confirmed by the conversion of 5-methylcytosine (5-mc) into 5-hydroxy methylcytosine (5hmC). DNA methyltransferases regulate DNA methylation. Next, we checked the effect of EGCG on the expression levels of DNA methyltransferases (DNMTs) and DNMT activity. Treatment of EGCG to HNSCC cells significantly reduced DNMT activity to 60% in SCC-1 and 80% in FaDu cells. The protein levels of DNMT3a and DNMT3b were downregulated in both cell lines after EGCG treatment. EGCG treatment to HNSCC cells reactivated tumor suppressors and caused decreased cell proliferation. Our in vivo study demonstrated that administration of EGCG (0.5%, w/w) as a supplement within an AIN76A diet resulted in inhibition of tumor growth in FaDu xenografts in nude mice (80%; p < 0.01) compared with non-EGCG-treated controls. The growth inhibitory effect of dietary EGCG on the HNSCC xenograft tumors was associated with the inhibition of DNMTs and reactivation of silenced tumor suppressors. Together, our study provides evidence that EGCG acts as a DNA demethylating agent and can reactivate epigenetically silenced tumor suppressors to inhibit the growth of HNSCC cells.

LCN2-Fungal siderophore-iron binding and uptake leads to oxidative stress and cell death in hepatocellular carcinoma cell line HepG2.

Microorganisms produce non-ribosomal peptides called siderophores for the purpose of iron acquisition. Mammalian immune system is well-known for producing small secretory proteins called lipocalins upon bacterial infection. These proteins sequester siderophores produced by invading bacterial pathogens rendering them unable to acquire iron from the host. However, this is not their sole function. In addition to transferrin and lactoferrin, lipocalins are also known to transport siderophore-bound iron to the host cells. While binding of bacterial siderophores with human lipocalin is well studied, binding of the fungal counterpart is still not confirmed and fully understood. Apart from pathogen-affected cells, developing cancerous cells also show varying expression level of different proteins including those involved in iron transport. The possibility of exogenous fungal siderophore-mediated iron transport via lipocalin and its receptor in mammalian cells has not yet been explored much. In present investigation we have checked differential expression of human lipocalin, LCN2 in hepatocellular carcinoma cell lines HepG2 as well as its normal counterpart WRL-68 and computationally determined the feasibility of LCN2 binding with fungal siderophore. Further in case of a stable complex being formed, whether this complex has the ability to transport iron through its specific receptor was assessed. Also, we have tried to explore possible mechanism of fungal-siderophore mediated oxidative stress leading to significant cell death in cancerous cells. This study will thus be useful towards finding a new way of treating hepatocellular carcinoma via inducing siderophore-mediated cell death in cancerous cells.Communicated by Ramaswamy H. Sarma.

Impact of climate change induced future rainfall variation on dynamics of arid-humid zone transition in the western province of India.

The transition of the Earth's climate from one zone to another is one of the major causes behind biodiversity loss, rural-urban migration, and increasing food crises. The rising rate of arid-humid zone transition due to climate change has been substantially visible in the last few decades. However, the precise quantification of the climate change-induced rainfall variation on the climate zone transition still remained a challenge. To solve the issue, the Representative Grid Location-Multivariate Adaptive Regression Spline (RGL-MARS) downscaling algorithm was coupled with the Koppen climate classification scheme to project future changes in various climate zones for the study area. It was observed that the performance of the model was better for the humid clusters compared to the arid clusters. It was noticed that, by the end of the 21st century, the arid region would increase marginally and the humid region would rise by 24.28-36.09% for the western province of India. In contrast, the area of the semi-arid and semi-humid regions would decline for the study area. It was observed that there would be an extensive conversion of semi-humid to humid zone in the peripheral region of the Arabian sea due to the strengthening of land-sea thermal contrast caused by climate change. Similarly, semi-arid to arid zone conversion would also increase due to the inflow of dry air from the Arabian region. The current research would be helpful for the researchers and policymakers to take appropriate measures to reduce the rate of climate zone transition, thereby developing the socioeconomic status of the rural and urban populations.

In silico analysis of comparative affinity of phytosiderophore and bacillibactin for iron uptake by YSL15 and YSL18 receptors of Oryza sativa.

Iron is an important micronutrient for plant growth and development. In the case of Oryza sativa, iron is made available primarily with the help of iron chelators called phytosiderophores i.e. variants of deoxymugineic acid (DMA). They bind with ferric ions and get internalized through Yellow Stripe Like transporters viz. YSL15 and YSL18. However, due to low amount of secretion of phytosiderophores, rice suffers from iron deficiency. Alternatively, siderophores of plant growth promoting rhizobacteria may support iron uptake and make it available to plants via transporting ferric ions possibly through the same transporters. Present study aims to assess comparative binding of DMA and a xenosiderophore (siderophores used by organisms other than the ones producing them) of rhizobacteria i.e. bacillibactin with Fe3+ ion and subsequent transporters of rice. Protein-protein interaction and gene expression analysis predicts uptake of Fe3+ by YSL15 from the rhizosphere region and further distribution through YSL18 with the help of various predicted functional partners. Docking studies confirm the thermodynamically more favourable structure of bacillibactin-Fe3+ complex than DMA-Fe3+ complex. Molecular modelling of YSL15 and YSL18 was done through ab initio method and their evaluation by Ramachandran plot, ProSA, ERRAT value and verify 3 D score revealed a good quality models. Comparative binding assessment through docking and molecular dynamics simulation suggests better binding energies of YSL transporters with bacillibactin-Fe3+ complex as compared to DMA-Fe3+ complex. The current study suggests possible application of xenosiderophores of PGPR origin in supporting plant growth via iron uptake and distribution in rice.Communicated by Ramaswamy H. Sarma.

Neuroprotective effect of phytoconstituents via nanotechnology for treatment of Alzheimer diseases.

Alzheimer's disease (AD) is a neurological condition characterised by cognitive and behavioural dysfunction. The presence of the blood brain barrier (BBB), which prevents medications from entering the brain, makes treating AD difficult. Currently, existing therapeutic modalities provide symptomatic alleviation while also being unsafe. Phytoconstituents are gaining popularity due to their neuroprotective properties and ability to target many pathogenic pathways involved with AD. However, because to their lower BBB permeability, poor solubility, and low bioavailability, they have failed to reduce disease progression and treat Alzheimer's disease. Nanotechnology is an emerging tool for overcoming these obstacles in brain drug delivery. Thus, the development of phytochemical-loaded nanocarrier systems can reduce these barriers while improving neuroprotective benefits. In this review, we summarised prospective targets, methodologies for brain drug delivery, phytoconstituents, and their nanocarrier system developed for the management and treatment of AD. Researchers looking for an alternate method to treat AD were given new insight by emphasising obstacles and future prospects.