Interplay of precision therapeutics and MD study: Calocybe indica's potentials against cervical cancer and its interaction with VEGF via octadecanoic acid.

The evolving landscape of personalized medicine necessitates a shift from traditional therapeutic interventions towards precision-driven approaches. Embracing this paradigm, our research probes the therapeutic efficacy of the aqueous crude extract (ACE) of Calocybe indica in cervical cancer treatment, merging botanical insights with advanced molecular research. We observed that ACE exerts significant influences on nuclear morphology and cell cycle modulation, further inducing early apoptosis and showcasing prebiotic attributes. Characterization of ACE have identified several phytochemicals including significant presence of octadeconoic acid. Simultaneously, utilizing advanced Molecular Dynamics (MD) simulations, we deciphered the intricate molecular interactions between Vascular Endothelial Growth Factor (VEGF) and Octadecanoic acid to establish C.indica's role as an anticancer agent. Our study delineates Octadecanoic acid's potential as a robust binding partner for VEGF, with comprehensive analyses from RMSD and RMSF profiles highlighting the stability and adaptability of the protein-ligand interactions. Further in-depth thermodynamic explorations via MM-GBSA calculations reveal the binding landscape of the VEGF-Octadecanoic acid complex. Emerging therapeutic innovations, encompassing proteolysis-targeting chimeras (PROTACs) and avant-garde nanocarriers, are discussed in the context of their synergy with compounds like Calocybe indica P&C. This convergence underscores the profound therapeutic potential awaiting clinical exploration. This study offers a holistic perspective on the promising therapeutic avenues facilitated by C. indica against cervical cancer, intricately woven with advanced molecular interactions and the prospective integration of precision therapeutics in modern oncology.

Molecular insights into phosphoethanolamine cellulose formation and secretion.

Phosphoethanolamine (pEtN) cellulose is a naturally occurring modified cellulose produced by several Enterobacteriaceae. The minimal components of the E. coli cellulose synthase complex include the catalytically active BcsA enzyme, an associated periplasmic semicircle of hexameric BcsB, as well as the outer membrane (OM)-integrated BcsC subunit containing periplasmic tetratricopeptide repeats (TPR). Additional subunits include BcsG, a membrane-anchored periplasmic pEtN transferase associated with BcsA, and BcsZ, a conserved periplasmic cellulase of unknown biological function. While events underlying the synthesis and translocation of cellulose by BcsA are well described, little is known about its pEtN modification and translocation across the cell envelope. We show that the N-terminal cytosolic domain of BcsA positions three copies of BcsG near the nascent cellulose polymer. Further, the terminal subunit of the BcsB semicircle tethers the N-terminus of a single BcsC protein to establish a trans-envelope secretion system. BcsC's TPR motifs bind a putative cello-oligosaccharide near the entrance to its OM pore. Additionally, we show that only the hydrolytic activity of BcsZ but not the subunit itself is necessary for cellulose secretion, suggesting a secretion mechanism based on enzymatic removal of mislocalized cellulose. Lastly, we introduce pEtN modification of cellulose in orthogonal cellulose biosynthetic systems by protein engineering.

Characterization of AICAR transformylase/IMP cyclohydrolase (ATIC) bifunctional enzyme from Candidatus Liberibacer asiaticus.

The bifunctional enzyme, 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) transformylase/inosine monophosphate (IMP) cyclohydrolase (ATIC) is involved in catalyzing penultimate and final steps of purine de novo biosynthetic pathway crucial for the survival of organisms. The present study reports the characterization of ATIC from Candidatus Liberibacer asiaticus (CLasATIC) along with the identification of potential inhibitor molecules and evaluation of cell proliferative activity. CLasATIC showed both the AICAR Transformylase (AICAR TFase) activity for substrates, 10-f-THF (Km, 146.6 µM and Vmax, 0.95 µmol/min/mg) and AICAR (Km, 34.81 µM and Vmax, 0.56 µmol/min/mg) and IMP cyclohydrolase (IMPCHase) activitiy (Km, 1.81 µM and Vmax, 2.87 µmol/min/mg). The optimum pH and temperature were also identified for the enzyme activity. In-silico study has been conducted to identify potential inhibitor molecules through virtual screening and MD simulations. Out of many compounds, HNBSA, diosbulbin A and lepidine D emerged as lead compounds, exhibiting higher binding energy and stability for CLasATIC than AICAR. ITC study reports higher binding affinities for HNBSA and diosbulbin A (Kd, 12.3 µM and 34.2 µM, respectively) compared to AICAR (Kd, 83.4 µM). Likewise, DSC studies showed enhanced thermal stability for CLasATIC in the presence of inhibitors. CD and Fluorescence studies revealed significant conformational changes in CLasATIC upon binding of the inhibitors. CLasATIC demonstrated potent cell proliferative, wound healing and ROS scavenging properties evaluated by cell-based bioassays using CHO cells. This study highlights CLasATIC as a promising drug target with potential inhibitors for managing CLas and its unique cell protective, wound-healing properties for future biotechnological applications.

Fenugreek derived diosgenin as an emerging source for diabetic therapy.

Diabetes is a chronic metabolic disease that endangers the entire body's tissues and organs. Diabetes impairs glucose and insulin regulation in the human body by causing pancreatic cell damage. Diabetes modifies pathways such as serine/threonine protein kinase (Akt) and Protein kinase C (PKC)/- glucose transporter 4 (GLUT4), peroxisome proliferator-activated receptor (PPAR) glucose absorption, and inhibits α-amylase and α-glucosidase, Sodium/glucose cotransporter 1 (SGLT-1), and Na+-K+-ATPase activity. Diabetes may also be caused by a decrease in the expression of sterol regulatory element binding protein 1 (SREBP-1) and its target genes, fatty acid synthase (FAS), stearoyl-CoA desaturase-1 (SCD-1), and acetyl-CoA carboxylase α (ACC), as well as a decrease in the levels of C/EBP homologous protein (CHOP), Caspase12, and Caspase3 proteins. Diabetes has long been linked to diseases of the cardiovascular, nervous, skeletal, reproductive, hepatic, ocular, and renal systems. Diosgenin, a steroidal compound derived from fenugreek, aids in the prevention of diabetes by altering cellular pathways in favor of healthy bodily functions. Diosgenin is a new nutraceutical on the market that claims to cure diabetes in particular. This article focuses on diosgenin extraction and purification, fenugreek bioactive compounds, pharmacological properties of diosgenin, mode of action of diosgenin to cure diabetes, and dosages.

Insights into substrate coordination and glycosyl transfer of poplar cellulose synthase-8.

Cellulose is an abundant cell wall component of land plants. It is synthesized from UDP-activated glucose molecules by cellulose synthase, a membrane-integrated processive glycosyltransferase. Cellulose synthase couples the elongation of the cellulose polymer with its translocation across the plasma membrane. Here, we present substrate- and product-bound cryogenic electron microscopy structures of the homotrimeric cellulose synthase isoform-8 (CesA8) from hybrid aspen (poplar). UDP-glucose binds to a conserved catalytic pocket adjacent to the entrance to a transmembrane channel. The substrate's glucosyl unit is coordinated by conserved residues of the glycosyltransferase domain and amphipathic interface helices. Site-directed mutagenesis of a conserved gating loop capping the active site reveals its critical function for catalytic activity. Molecular dynamics simulations reveal prolonged interactions of the gating loop with the substrate molecule, particularly across its central conserved region. These transient interactions likely facilitate the proper positioning of the substrate molecule for glycosyl transfer and cellulose translocation.

Insights into substrate coordination and glycosyl transfer of poplar cellulose synthase-8.

Cellulose is an abundant cell wall component of land plants. It is synthesized from UDP-activated glucose molecules by cellulose synthase, a membrane-integrated processive glycosyltransferase. Cellulose synthase couples the elongation of the cellulose polymer with its translocation across the plasma membrane. Here, we present substrate and product-bound cryogenic electron microscopy structures of the homotrimeric cellulose synthase isoform-8 (CesA8) from hybrid aspen (poplar). UDP-glucose binds to a conserved catalytic pocket adjacent to the entrance to a transmembrane channel. The substrate's glucosyl unit is coordinated by conserved residues of the glycosyltransferase domain and amphipathic interface helices. Site-directed mutagenesis of a conserved gating loop capping the active site reveals its critical function for catalytic activity. Molecular dynamics simulations reveal prolonged interactions of the gating loop with the substrate molecule, particularly across its central conserved region. These transient interactions likely facilitate the proper positioning of the substrate molecule for glycosyl transfer and cellulose translocation. Highlights: Cryo-EM structures of substrate and product bound poplar cellulose synthase provide insights into substrate selectivitySite directed mutagenesis signifies a critical function of the gating loop for catalysisMolecular dynamics simulations support persistent gating loop - substrate interactionsGating loop helps in positioning the substrate molecule to facilitate cellulose elongationConserved cellulose synthesis substrate binding mechanism across the kingdoms.

Expression profile of different classes of proteases in milk derived somatic cells across different lactation stages of indigenous cows (Bos indicus) and riverine buffaloes (Bubalus bubalis).

Proteases play a significant role in milk and its products by affecting flavor, texture and longevity. The expression of endogenous proteases varies across different stages of lactation. The study was conducted to understand the transcriptional pattern of different classes of protease-pathways associated genes (CTSB, CTSD, CTSH, CTSL, CTSK, CTSS, CTSZ, PLAU, PLAT) and potential protease inhibitors (SERPIN E2 and SERPIN F2) in 40 milk somatic cells (MSC) samples isolated during early, peak, mid and late lactation stages of Sahiwal cows and Murrah buffaloes - the two most important dairy breeds of India. In Sahiwal cows, except CTSK and PLAU, the expression of other proteases class was not affected significantly (p > 0.05) across lactation stages. However, in Murrah buffaloes, the expression of different proteases increased as the lactation progressed. Most of the proteases showed lower expression during early and peak lactation stages while their expression tends to increase during mid to late lactation stages. The overall trend was somewhat similar in both the dairy species albeit the level of expression was higher in buffalo MSC as compared to cow MSC. The study has provided valuable information on expression kinetics of different proteases in milk somatic cells of two major dairy breeds of India.

Selection of species specific panel of reference genes in peripheral blood mononuclear cells of native livestock species adapted to trans-Himalayan region of Leh-Ladakh.

The identification of appropriate references genes is an integral component of any gene expression-based study for getting accuracy and reliability in data interpretation. In this study, we evaluated the expression stability of 10 candidate reference genes (GAPDH, RPL4, EEF1A1, RPS9, HPRT1, UXT, RPS23, B2M, RPS15, ACTB) in peripheral blood mononuclear cells of livestock species that are adapted to high altitude hypoxia conditions of Leh-Ladakh. A total of 37 PBMCs samples from six native livestock species of Leh-Ladakh region such as Ladakhi cattle, Ladakhi yak, Ladakhi donkey, Chanthangi goat, Double hump cattle and Zanskar ponies were included in this study. The commonly used statistical algorithms such as geNorm, Normfinder, BestKeeper and RefFinder were employed to assess the stability of these RGs in all the livestock species. Our study has identified different panel of reference genes in each species; for example, EEF1A1, RPL4 in Ladakhi cattle; GAPDH, RPS9, ACTB in Ladakhi yak; HPRT1, B2M, ACTB in Ladakhi donkey; HPRT1, B2M, ACTB in Double hump camel, RPS9, HPRT1 in Changthangi goat, HPRT1 and ACTB in Zanskar ponies. To the best of our knowledge, this is the first systematic attempt to identify panel of RGs across different livestock species types adapted to high altitude hypoxia conditions. In future, the findings of the present study would be quite helpful in conducting any transcriptional studies to understand the molecular basis of high altitude adaptation of native livestock population of Leh-Ladakh.

In Silico Analysis of the Apoptotic and HPV Inhibitory Roles of Some Selected Phytochemicals Detected from the Rhizomes of Greater Cardamom.

Occurrence of cervical cancer, caused due to persistent human papilloma virus (HPV) infection, is common in women of developing countries. As the conventional treatments are expensive and associated with severe side effects, there is a need to find safer alternatives, which is affordable and less toxic to the healthy human cells. Present study aimed to evaluate the anti-HPV and apoptotic potential of four compounds from the greater cardamom (Amomum subulatum Roxb. var. Golsey), namely rhein, phytosphingosine, n-hexadecenoic acid and coronarin E. Their anti-HPV and apoptotic potential were studied against viral E6, E7 and few anti-apoptotic proteins of host cell (BCL2, XIAP, LIVIN) by in silico docking technique. Phytochemicals from the plant extract were analysed and identified by LC/MS and GC/MS. Involvement of the target proteins in various biological pathways was determined through KEGG. Structural optimization of the three-dimensional structures of the ligands (four phytochemicals and control drug) was done by Avogadro1.1. Receptor protein models were built using ProMod3 and other advanced tools. Pharmacophore modelling of the selected phytochemicals was performed in ZINCPharmer. Swiss ADME studies were undertaken to determine drug likeness. The ligands and proteins were digitally docked in DockThor docking program. Protein flexibility-molecular dynamic simulation helped to study protein-ligand stability in real time. Finally, the correlation of evaluated molecules was studied by the use of principal component analysis (PCA) based on the docking scores. All the ligands were found to possess apoptotic and anti-cancer activities and did not violate Lipinsky criteria. n-Hexadecanoic acid and its analogues showed maximum efficacy against the target proteins. All the protein-ligand interactions were found to be stable. The uncommon phytochemicals identified from rhizomes of greater cardamom have anti-cancer, apoptotic and HPV inhibitory potentials as analysed by docking and other in silico studies, which can be utilized in drug development after proper experimental validation.

SAXS Analysis and Characterization of Anticancer Activity of PNP-UDP Family Protein from Putranjiva roxburghii.

A class of plant defense and storage proteins, including Putranjiva roxburghii PNP protein (PRpnp), belongs to PNP-UDP family. The PRpnp and related plant proteins contain a disrupted PNP-UDP domain as revealed in previous studies. In PRpnp, the insert disrupting the domain contains the trypsin inhibitory site. In the present work, we analyzed native PRpnp (nPRpnp) complex formation with trypsin and inosine using SAXS experiments and established its dual functionality. Results indicated a relatively compact nPRpnp:Inosine structure, whereas trypsin complex showed conformational changes/flexibility. nPRpnp also exhibited a strong anti-cancer activity toward breast cancer (MCF-7), prostate cancer (DU-145) and hepatocellular carcinoma (HepG2) cell lines. MCF-7 and DU-145 were more sensitive to nPRpnp treatment as compared to HepG2. However, nPRpnp treatment showed no effect on the viability of HEK293 cells indicating that nPRpnp is specific for targeting the viability of only cancer cells. Further, acridine orange, DAPI and DNA fragmentation studies showed that cytotoxic effect of nPRpnp is mediated through induction of apoptosis as evident from the apoptosis-associated morphological changes and nuclear fragmentation observed after PRpnp treatment of cancer cells. These results suggest that PRpnp has the potential to be used as an anticancer agent. This is first report of anticancer activity as well as SAXS-based analysis for a PNP enzyme with trypsin inhibitory activity.

Independent and combined influences of physical activity, screen time, and sleep quality on adiposity indicators in Indian adolescents.

BACKGROUND: Inadequate physical activity (PA), excess screen time (ST), and sub-optimal sleep quality tend to co-occur during adolescence. Yet, little is known about the associations of these behaviors as a cluster with adiposity indicators in Indian adolescents. This study aimed to evaluate the independent and combined influences of PA, ST, and sleep quality on body mass index (BMI) and waist to height ratio (WHtR) in 10-15 years old adolescents in Mumbai, India. A secondary aim was to explore if these influences vary between sexes. METHODS: Cross-sectional study. Adolescents (n = 772, mean age 13.2 (1.4) years) reported frequency and duration of moderate to vigorous PA (MVPA) and time spent using screens on a previously validated instrument. Sleep quality was estimated using the Pittsburg Sleep Quality Index (PSQI). Weight, height, and waist circumference were measured. Mixed effect logistic regression analyses were performed to explore associations between adiposity indicators (BMI z scores > +1SD and WHtR > 0.5) and unhealthy behaviors (PA < 60 min/d, ST > 120 min/d and PSQI scores > 5), stratified by sex. RESULTS: The combined prevalence of overweight and obesity was 38.3%. Overall, 62.0 and 85.0% reported MVPA< 60 min/d and ST > 120 min/d respectively. Girls reported higher ST (218.21 (69.01) min/d) as compared to boys (165.3 (101.22) min/d, p < 0.001). Clustering of low PA and excess ST was observed in 69.2% and of all three unhealthy behaviors in 18.8%. Among girls, MVPA < 60 min/d (OR = 1.78, 95% CI 1.54-1.92, p < 0.001) and PSQI scores > 5 (OR = 2.01, 95% CI 1.78-2.25, p < 0.001) predicted increased BMI. The odds of overweight/obesity were 2.10 times higher in boys reporting low PA and 4.13 times higher in those with low PA+ ST > 120 min/d. Clustering of all three unhealthy behaviors increased prevalence of obesity in both sexes. CONCLUSIONS: The results indicated a co-existence of multiple unhealthy lifestyle factors of obesity and that clustering of these behaviors can further aggravate obesity risk as compared to their independent effects. Integrated interventions that leverage the cumulative benefits of being active, less sedentary and sufficient sleep are warranted to facilitate greater improvements in obesity risk behaviors.

Development and validation of a questionnaire measuring knowledge, attitudes, and practices (KAP) to healthy eating and activity patterns in school children (HEAPS).

BACKGROUND: Development of culturally appropriate and psychometrically sound instruments that measure knowledge and health behaviors of children will help to inform appropriate interventions. AIM: To develop and test the validity and reliability of a questionnaire measuring knowledge, attitudes, and practices to healthy eating and activity patterns in school children in India. METHODS: Review of literature, focus-group discussions, and theoretical constructs of the Health Belief Model guided the development of an item pool. Face and content validity were assessed by children and a panel of experts and the item content validity, item difficulty, and discrimination indices were calculated. Construct validity was determined using the principal axis method of exploratory factor analysis among a cross-sectional sample of children (n=252). Internal consistency (Cronbach α values >0.7) and test-retest reliability (intraclass correlation coefficient values >0.75) were estimated. RESULTS: Item content validity index for clarity and relevance were satisfactory (>0.80) and internal consistency for knowledge (Kuder-Richardson 20 = 0.832), attitude (Cronbach's α = 0.912), and practice items (Cronbach's α = 0.769) were good. Four factors (children's eating habits, family dietary practices, and consumption of healthy and unhealthy foods) and two factors (moderate to vigorous activities and sedentary activities) explained 67.7% and 48.2% of the total variance in practice items. Intraclass correlation coefficient estimates ranged from good to excellent (0.72-0.99). CONCLUSIONS: The results of the validity and reliability of the 84-item knowledge, attitudes, and practices to healthy eating and activity patterns in schoolchildren questionnaire were promising. The detailed description of the methodology employed may prove useful to researchers conducting similar studies in children.

Two species of Ulva inhibits the progression of cervical cancer cells SiHa by means of autophagic cell death induction.

Edible green algal seaweeds, namely Ulva intestinalis and Ulva lactuca constitute a significant repository of popular herbal medicines in the Traditional Chinese Medicinal system. The present study aimed to assess the anticancer potential of these algal members and its mode of action in cervical cancer cells SiHa. The algal samples primarily extracted in methanol was fractionated into hexane, chloroform, and aqueous algal fractions, which inhibited the proliferation of SiHa cells in a dose-dependent manner, with the algal chloroform fractions harbouring the lowest IC50 dose of 141.38 µg/ml in U. intestinalis and 445.278 µg/ml in U. lactuca. These algal chloroform fractions when studied for their in-depth mode of action, were found to damage and pulverise the nuclei, resulting in a concomitant increase in subG0-phase of SiHa cells, studied by flow cytometry. The algal treatment also caused an increase in the number of acidic vesicles and enhanced the expression of LC3BII, p62 and atg12 proteins, which together pointed out autophagy as the induced mode of cell death. Upregulated Bax and p53 expression along with decreased Bcl2 expression also correlated to autophagic cell death. Decreased expression of E6 viral oncogene was noted as a significant response to algal fractions. Lastly, these potent algal fractions when characterised pharmacologically through GC-MS analysis were found to be rich in unsaturated fatty acids, majorly palmitic acid. Hence, this study concludes that the two species of Ulva successfully decreased the proliferation of SiHa cervical cancer cells through autophagy, hinting at palmitic acid being the major responsible bioactive compound in both.

Impact of a behaviourally focused nutrition education intervention on attitudes and practices related to eating habits and activity levels in Indian adolescents.

OBJECTIVE: To evaluate the effectiveness of a behaviourally focused nutrition education (NE) intervention based on the Health Belief Model (HBM) to improve knowledge, attitudes and practices (KAP) related to eating habits and activity levels in 10­12-year-old adolescents in Mumbai, India. DESIGN: School-based cluster randomised controlled trial. The experimental group (EG) received weekly NE and three parent sessions over 12 weeks; no sessions were conducted for the control group (CG). The theoretical framework of HBM and focus group discussion results guided the development of behaviour change communication strategies and NE aids. KAP were measured using a validated survey instrument, administered at baseline and endline in EG and CG. Paired and independent t tests determined within-group and between-group changes in pre­post scores. SETTING: Two aided and two private schools that were randomly allocated to either an EG or CG. PARTICIPANTS: Adolescent boys and girls (n 498; EG n 292 and CG n 206). RESULTS: EG reported improvements in mean knowledge (39·3%), attitude (7·3 %), diet (9·6 %) and activity practice (9·4%) scores from pre to post intervention. No significant changes were observed in CG. Significant improvements in scores associated with perceived benefits, barriers and self-efficacy, breakfast and vegetable consumption, and moderate-to-vigorous activities were observed in EG. CONCLUSIONS: Integrating NE into the academic curriculum and adopting evidence-based lessons that entail targeted information delivery and participatory activities can improve knowledge, foster right attitudes and facilitate better eating and activity-related practices in Indian adolescents.

Identification of Internal Reference Genes in Peripheral Blood Mononuclear Cells of Cattle Populations Adapted to Hot Arid Normoxia and Cold Arid Hypoxia Environments.

To estimate gene expression in a reliable manner, quantitative real-time polymerase chain reaction data require normalisation using a panel of stably expressed reference genes (RGs). To date, information on an appropriate panel of RGs in cattle populations reared at cold arid high-altitude hypoxia and hot arid tropical normoxia environments is not available. Therefore, the present study was carried out to identify a panel of stably expressed RGs from 10 candidate genes (GAPDH, RPL4, EEF1A1, RPS9, HPRT1, UXT, HMBS, B2M, RPS15, and ACTB) in peripheral blood mononuclear cells (PBMCs) of cattle populations reared at cold arid high-altitude hypoxia and hot arid normoxia environments. Four different statistical algorithms: geNorm, NormFinder, BestKeeper, and RefFinder were used to assess the stability of these genes. A total of 30 blood samples were collected: six adult heifers each of Ladakhi (LAC) and Holstein Frisian crosses (HFX) and 4 Jersey (JYC) cows from cold arid high-altitude hypoxia environments (group I) and five adult heifers each of Sahiwal (SAC), Karan Fries (KFC), and Holstein Friesian (HFC) cows from hot arid normoxia environments (group II). Combined analysis of group I and group II resulted in identification of a panel of RGs like RPS9, RPS15, and GAPDH that could act as a useful resource to unravel the accurate transcriptional profile of PBMCs from diverse cattle populations adapted to distinct altitudes.

Effect of nitrogen (N) deposition on soil-N processes: a holistic approach.

Nitrogen (N) deposition is a serious environmental issue for soil fertility and human wellbeing. Studies on various terrestrial ecosystems yielded fragmented information on soil-N status (microbial biomass- and mineral-N) and dynamics (N-mineralization and -leaching) whereas the holistic view on this issue is relatively unknown. A complete understanding of soil-N status and dynamics in response to N deposition is essential for sustainable management of ecosystem structure and function as needed for human wellbeing. Therefore, we conducted an experiment in the N-limited tropical grassland to explore the question whether N-deposition weakens the soil-N status and dynamics; if yes, then what could be the optimum amount of deposited N and the related controlling mechanism? We undertook a 3-year (2013-2016) experimental N fertilization (control, 30, 60, 90, 120, and 150 kg N ha-1 year-1) study (using urea as a source of N deposition). The data from a total of 72, 1 × 1 m plots (six treatments with 12 replicates) were collected and properly analysed with statistical software. N deposition caused significant differences in the parameters of soil-N status and dynamics. The responses of microbial biomass-N, N-mineralization, and mineral-N to the N deposition were quadratic (maximum values were in N90) whereas N-leaching showed a linear response. Compared to control, N deposition (30-150 kg N) consistently enhanced (29-96%) leaching of N. As a mechanism, acidification induced aluminium toxicity, carbon to nitrogen ratio and litter decomposition governed the soil-N status and dynamics. N deposition over and above 90 kg ha-1 year-1 resulted in a negative feedback to soil N transformation and availability. Hence, N deposition below 90 kg ha-1 year-1 could be a limit for the sustainable functioning of the tropical or similar grasslands.

Oleogel-mediated transdermal delivery of white emitting NaYF4 conjugated with Rose Bengal for the generation of reactive oxygen species through NIR-upconversion.

The transdermal route for the delivery of therapeutic agents to the inner skin tissues for non-invasive photodynamic therapy; though constitutes a desired modality for treating skin cancer, the success has been limited due to the insurmountable nature of the stratum corneum (SC). In this context, for the first time we report the localization of photosensitizer-conjugated upconversion (UC) particles to the deeper dermal region by overcoming SC through an oleogel-mediated transport mechanism for NIR-induced photodynamic production of reactive oxygen species (ROS). We developed soybean oil and stearic acid based oleogels by incorporating photoluminescent white light emitting NaYF4 (WEN) upconversion (UC) particles conjugated with Rose Bengal (RB), termed as WEN-RB-G. Similarly, we fabricated another type of oleogel by incorporating Li+ doped WEN based UC particles (RB conjugated), with 10 times more photoluminescence intensity, termed as LiWEN-RB-G. Based on the skin permeation enhancing effect of the constituents of the oleogels, we demonstrated the permeation of these two types of conjugated particles in microgram scale through the full thickness of the pig ear skin model within 48 h. The localization of the conjugated particles throughout the skin tissue including dermal and epidermal region was confirmed by confocal microscopy. We also conducted a comparative assessment on WEN-RB-G and LiWEN-RB-G for the suitability of ROS generation and bioimaging under NIR activation. The 'proof of principle' concept reported here is expected to frame a gateway in future for NIR-induced photo-theranostics targeting skin cancer.

Novel fatty acid-thiadiazole derivatives as potential antimycobacterial agents.

The discovery of antibiotics around the middle twentieth century led to a decrease in the interest in antimycobacterial fatty acids. In order to re-establish the importance of naturally abundant fatty acid, a series of fatty acid-thiadiazole derivatives were designed and synthesized based on molecular hybridization approach. In vitro antimycobacterial potential was established by a screening of synthesized compounds against Mycobacterium tuberculosis H37Rv strain. Among them, compounds 5a, 5d, 5h, and 5j were the most active, with compound 5j exhibiting minimum inhibitory concentration of 2.34 µg/ml against M.tb H37Rv. Additionally, the compounds were docked to determine the probable binding interactions and understand the mechanism of action of most active molecules on enoyl-acyl carrier protein reductases (InhA), which is involved in the mycobacterium fatty acid biosynthetic pathway.

Determining the cutoff of rainfall for Plasmodium falciparum malaria outbreaks in India.

BACKGROUND: Malaria outbreaks due to Plasmodium falciparum have been reported from various parts of India. Rainfall is considered as one of the major determinants for malaria outbreaks, however, an estimate of rainfall threshold for malaria is not known. Owing to the vast geographic area, the present study was planned to determine the amount of rainfall required for malaria outbreaks and the lag period between outbreak and rainfall in different Indian climatic regions. METHODS: Simple statistical methods of overall mean and moving mean (case/mean ratio, CMR) were used to identify the districts with P. falciparum malaria outbreak due to rainfall and the amount of rainfall required for outbreaks. Of 120 districts reporting P. falciparum malaria outbreaks, 99 districts having substantially low number of cases (<100); <3 CMR in any year from 2009 to 2012 and districts having stable malaria transmission were excluded. Finally, analysis of outbreak month, lag period and the threshold of rainfall were determined in respect of 21 districts which represent different agro-climatic zones in the country. Whenever the moving mean of cases attained the value ≥3 in any month, that month was identified as P. falciparum malaria outbreak. The threshold amount of rainfall critical for malaria outbreak was calculated by the average mean of previous months (i.e., lag period). RESULTS: The rainfall cutoff ranged from >70 to >600mm in different districts. The month of outbreak varied with the climatic zones viz. arid, semi-arid, humid and per-humid districts. In humid and per-humid districts, outbreaks occurred during monsoon period whereas in arid and semi-arid regions outbreaks occurred during the post monsoon period. The lag period varied from 1-3 months; long lag period was observed in arid, semi-arid region, while short lag period in humid and per-humid regions. CONCLUSION: Malaria outbreaks can occur in post monsoon in arid and semi-arid region whereas in summer/monsoon in humid and per-humid regions. The lag period between rainfall and outbreak differs from one month with short lag (humid and per-humid) to long lag (arid and semi-arid). Based on the determined threshold of rainfall, the findings would be helpful in forewarning of imminent outbreak of malaria for the timely preparedness of malaria outbreaks not only in 21 studied districts, but also in several other districts of different climatic regions of India.

Responses of diversity, productivity, and stability to the nitrogen input in a tropical grassland.

Atmospheric nitrogen (N) deposition is a matter of serious concern for the structure and functioning of global ecosystems, but the effect of N application of species diversity (D), primary productivity (P), and stability (S) of tropical grassland ecosystems is not known. The present study reports the effects of different levels of N application on species composition, and the D, P, S, and their relationships in a tropical grassland. Within the experimental grassland, 72 1 × 1 m plots with 6 N-input levels and with 12 replicates, were established in 2013. For 3 yr, different doses of urea as a source of N were applied to the plots. Data on individuals and biomass of each species were recorded and statistically analyzed. The study revealed that the N applied caused variations in species composition, D, P, and S. Below the 90 kg N dose, D was positively related to P and S while, above this level, the relations were negative due to N-induced responses of species and functional group composition as well as biomass distribution among them. The optimum applied N levels for maximum D (50-60 kg N), P (120 kg N), and a positive relationship of S with D (up to 90 kg N treatment) suggested that the 90-kg N dose could be the maximum dose of N that the grassland can tolerate. Hence, N application should not exceed the 90-kg level for sustainability of the structure and functioning of tropical grassland ecosystems.