Multidrug resistance is a major reason for drug resistance in patients undergoing chemotherapy or other drug therapy. The overexpression of efflux proteins, such as multidrug resistance protein or P-glycoprotein (P-gp), has been recognized as a major cause of the drugs' efflux from the brain. P-gp expression is not only responsible for drug resistance, but underactivity leads to the accumulation of amyloid proteins and may become one of the reasons for Alzheimer disease. Hence, measuring the activity of the efflux proteins can indicate whether the candidate is suitable for chemotherapy. Therefore, several radiotracers have been developed to image P-gp activity. Positron emission tomography imaging can assess P-gp function and, therefore, plays a crucial role in informing clinicians' decisions to adjust treatment. This review article discusses advancements in radiopharmaceuticals for imaging P-gp function and expression, particularly at the blood-brain barrier. It highlights the significance of various radiolabeled tracers, including verapamil, metoclopramide, and MC225, in assessing P-gp-mediated drug delivery to the brain and its role in various neurodisorders. This article discusses the outcomes of various radiopharmaceuticals used in imaging P-gp expression and function. SIGNIFICANCE STATEMENT: This review article highlights the evolution of radiopharmaceuticals for imaging P-gp in various disorders, including drug resistance, Alzheimer disease, and epilepsy. P-gp imaging can play a crucial role in drug development and aid in identifying tumors that are responsive or resistant to chemotherapy. It may help clinicians decide whether a patient is suitable for chemotherapy. Positron emission tomography imaging can provide information on P-gp activity, which can be assessed before and during chemotherapy.

The gram-negative coccobacillus Acinetobacter baumannii, a WHO critical priority pathogen and member of ESKAPE pathogen panel, threatens global health due to its substantial association with hospital-acquired infections as well as resistance exhibited to last-resort antibiotics, such as colistin, tigecycline and carbapenems. Thus, urgent drug discovery and development is essential, targeting Acinetobacter baumannii, especially carbapenem-resistant Acinetobacter baumannii (CRAB). In this context, we report the design, synthesis and anti-bacterial evaluation of a new collection of 5-(phenyl)-N'-arylisoxazole-3-carbohydrazides for their effectiveness against various bacterial pathogen panels. Amongst the various compounds synthesised, 7j, 7l, 7n, 7o, 7p, and 16 exhibited significant antibacterial activity against CRAB, with minimum inhibitory concentrations (MIC) 0.5-2 μg/mL. Compound 7l demonstrated the highest antibacterial effectiveness, with a 0.5 μg/mL MIC. Additional testing revealed that these compounds were non-toxic to Vero cells and displayed high selectivity indices. Furthermore, they were effective against clinical isolates of multidrug-resistant Acinetobacter baumannii (MDR-AB), with compound 7l showing bactericidal effects when paired with Rifampicin, as supported by time-kill kinetic studies. 3D QSAR confirms 7ls increased activity comes from good steric fit, ideal electrostatics, strategic hydrophobic placement, and precise H-bond acceptor/donor positioning, and 7l complies with Lipinski's rule of five. The molecular target for these compounds is not known, though in silico α-fold modelling indicate that KatG may be the probable target. However in-depth mechanistic studies need to be done to validate these in silico predictions, based on which 7l may be further optimised as a promising candidate targeting CRAB.

The escalating prevalence of multidrug-resistant tuberculosis (MDR-TB) underscores the urgent need for new classes of antitubercular agents targeting novel pathways. Carbonic anhydrase, a ubiquitous metalloenzyme, catalyses the reversible hydration of carbon dioxide in the CO2 + H2O ⇋ HCO3 - + H+ reaction. Suppressing this enzymatic activity has recently been identified as a new pathway for the treatment of Mycobacterium tuberculosis. To address this, a series of isoxazole-sulphonamides was rationally designed, incorporating an isoxazole pharmacophore as the aromatic tail, amide as a linker, and sulphonamide as the zinc-binding group. These compounds were evaluated against Mycobacterium tuberculosis carbonic anhydrases (MtCA 1 and 3) and two human carbonic anhydrases (hCA I and II) to identify selective inhibitors of the bacterial enzymes. The findings indicated that molecules containing an isoxazole pharmacophore with amide-linked benzene-3-sulphonamide were significantly more selective for MtCA 3 than hCA I and II. Among these compounds, 12c, 12e, and 19b had the highest inhibition against the MtCA 3 with K i values between 0.08-0.09 μM compared to the standard acetazolamide with a K i value of 0.10 μM. Some of the best compounds exhibited potent and selective inhibition of MtCA 3 over hCA I and II, with the meta- and para-substituted derivatives demonstrating higher selectivity and stronger inhibition. Specifically, compound 19b proved to be 199 and 38 times more selective for MtCA 3 than hCA I and hCA II respectively, compared to the standard drug acetazolamide, which is a non-selective CA inhibitor. The potential of compound 19b as a promising antitubercular agent with a MIC value of 8 μg mL-1 against mc2 6230 was further strengthened by in silico ligand-target interaction studies. Thus, compound 19b is emphasised as a promising lead in the pursuit of new, selective agents targeting MtCA 3.

Dehydroepiandrosterone (DHEA), a neurosteroid synthesized in the brain, declines significantly with age, making neurons more vulnerable to neuromodulatory changes. This study aimed to evaluate the neuroprotective potential of DHEA by analyzing its effects on acetylcholinesterase (ACh), tyrosine hydroxylase (TyrH), monoamine oxidase B (MAO-B), glucose transporter 4 (GLUT4) expression, membrane fluidity, neurolipofuscin, superoxide dismutase (SOD) activity, and cognitive performance. Behavioral tests and molecular analyses were performed in male rats of three age groups: young (4 months), adult (14 months), and old (24 months). The study also investigated whether DHEA administration could restore these parameters to youthful levels. Aged rats (14 and 24 months old) were administered daily subcutaneous injections of DHEA (30 mg/kg body weight) for one month. After treatment, animals were sacrificed, and synaptosomes were isolated for biochemical and molecular analyses. Cognitive performance was assessed using the Morris water maze, while ultrastructural changes in brain regions were evaluated through MRI. Aging was associated with significant increases in MAO-B activity, lipid peroxidation, and neurolipofuscin accumulation, alongside decreases in SOD activity, TyrH and ACh levels, membrane polarization, and GLUT4 expression. DHEA treatment significantly improved cognitive performance and memory in aging rats and elevated synaptic proteins, such as synaptophysin and synapsin I. Ultrastructural examination of the frontal cortex revealed reductions in lipofuscin and lysosomal degradation following DHEA administration. Biochemical parameters also returned to near-normal levels in aged rats treated with DHEA. This study highlights the therapeutic potential of DHEA as a neuroprotective and anti-aging agent. DHEA effectively mitigates age-related molecular, behavioral, and biochemical changes, suggesting its role as a promising adjunct therapy for addressing age-associated neuronal decline. Further research is warranted to explore its clinical implications.

In this study, we have labeled methacetin with carbon-11 [11C] as a PET imaging radiotracer. The radiolabeling was carried out by reacting acetaminophen with [11C]methyl iodide in the presence of a base using [11C]methyl iodide. [11C]methacetin was synthesized via methylation at 70 °C for 5 min with a radiochemical purity of 99.3 ± 0.4

Urban forests face multiple human-mediated pressures leading to compromised ecosystem structure and functioning. Therefore, understanding ecosystem structure in response to ongoing pressures is crucial for sustaining ecological integrity and human well-being. We aim to assess the disturbance and its effects on the vegetation structure of urban forests in Chandigarh using a combination of remote sensing techniques and vegetation surveys. The disturbance was evaluated as a change in NDVI (Normalised Difference Vegetation Index) from 2001 to 2021 by applying the BFAST (Breaks For Additive Season and Trend) algorithm to the MODIS satellite imagery data. A vegetation survey was conducted to compare the species composition, taxonomic and phylogenetic diversity as measures of forest vegetational structure. While signals of disturbance were evident, the changes in vegetation structure were not well established from our study. Further, this analysis indicated no significant differences in vegetation composition due to disturbance (F1,12 = 0.91, p = 0.575). However, the phylogenetic diversity was substantially lower for disturbed plots than undisturbed plots, though the taxonomic diversity was similar among the disturbed and undisturbed plots. Our results confirmed that disturbance effects are more prominent on the phylogenetic than taxonomic diversity. These findings can be considered early signals of disturbance and its impact on the vegetation structure of urban forests and contribute to the knowledge base on urban ecosystems. Our study has implications for facilitating evidence-based decision-making and the development of sustainable management strategies for urban forest ecosystems.

Background:Fluorine-18 (18F) flumazenil (FMZ) has been synthesized using various precursors, and its role has been explored in imaging Gamma-aminobutyric acid-A receptors.Aim and Objective:The main objective was to synthesize (18F) FMZ using isotopic substitution.Materials and Methods:Around 18 +/- 2 GBq was added to the module, dried, and radiolabeling was standardized with 3.0 mg of the FMZ precursor at various temperatures (110 degrees C -160 degrees C) for 10-30 min. The product was finally eluted with 20% ethanol (in phosphate buffer). The final product was characterized by high-performance liquid chromatography (HPLC). The stability was evaluated in water, saline, and phosphate-buffered saline for 4 h.Results:The radiolabelling efficiency of cartridge-based purification was 16 +/- 4% (n = 10) with a radiochemical purity of 96.5 +/- 1.8%, whereas in HPLC-based purification, the yield was 10 +/- 4% (n = 5) with a radiochemical purity of 97.3 +/- 1.4%. The specific activity was 120 +/- 20 GBq/mu mol.Conclusions:(18F) FMZ was successfully synthesized using an isotopic approach and could be used as an alternative cheaper option for the synthesis.

The assessment of tree biomass and its carbon (C) stock at the local and regional level is considered a crucial criterion for understanding the impact of changing environments on the global carbon cycle. In this context, we selected three sites in the western Himalayas, covering parts of Himachal Pradesh and north-eastern Haryana. Each study site experiences distinct climatic conditions, vegetation types, and elevations. We seek to elucidate the determinants of tree biomass and carbon stock across different forest types in the Western Himalayas. We found that temperate forests contributed the most biomass and carbon stock, with Cedrus deodara attaining the highest values of 782.6 ± 107.9 Mg/ha and 360 ± 49.7 Mg C/ha. In contrast, Quercus leucotrichophora mixed temperate had the lowest 286.6 ± 57.2 and 128.9 ± 25.7 Mg/C ha, respectively. Only a few species, such as Abies pindrow, Cedrus deodara, Quercus floribunda, and Quercus semecarpifolia, accounted for significant biomass and carbon stock. The lower elevation subtropical forests had the highest species richness (8–12 species) and stem density (558.3 ± 62.9 to 866.6 ± 57.7 trees/ha). Furthermore, tree diameter, total basal cover, and height emerged as the strongest predictors of biomass and C stock. The remaining variables showed no significant associations, including species diversity, climatic attributes and elevation. Thus, our study extended the assertion that vegetation composition and structural attributes, apart from climatic and topographic factors, are equally important in determining biomass and C stock in forest ecosystems. Our study indicated that the temperate forests in the western Himalayas possess significant carbon storage and climate change mitigation potential.

Urbanisation has emerged as a formidable challenge for urban policymakers, reaching unparalleled heights and unsettling the ecological equilibrium of the cities. Urban areas now grapple with many issues encompassing climate change, resource depletion, population surges and increased pollution levels. Many planned cities have planted trees and other vegetation within the urban sectors to enhance air quality, mitigate climate effects and provide valuable ecosystem services. This study assessed tree species diversity and their potential for carbon sequestration in Panjab University Campus, Chandigarh. We established 188 plots, each comprising randomly selected quadrats measuring 10 m × 10 m, encompassing areas with varying levels of vegetation, ranging from low to moderate and high density. We used four different allometric equations to estimate tree biomass and carbon stock. Our findings revealed that 92 tree species belong to 72 genera and 35 families, with a total tree density of 975 ha−1. The total CO2 sequestration in form of carbon stock was 18,769.46 Mg C ha−1, with Manilkara hexandra (1239.20 Mg C ha−1), Ficus benghalensis (1072.24 Mg C ha−1), Kigelia pinnata (989.89 Mg C ha−1) and Lagerstroemia floribunda (716.88 Mg C ha−1) being the top contributors. Specifically, the equation of Chave et al. (2005) without tree height yielded the highest biomass and carbon stock estimates than other equations. The present study underscores the vital role of trees on the campus as potent carbon reservoirs meet to maintain an aesthetic sense for biotic components and alleviate rising levels of CO2 in the atmospheric environment. By emphasising the role of urban trees as potent carbon reservoirs, the study underscores the importance of integrating green infrastructure into urban planning strategies. Furthermore, it offers valuable guidance for urban planners. It suggests that strategic tree planting and maintenance can enhance green spaces, regulate temperatures and ultimately support regional and global climate change mitigation goals. Incorporating these findings into urban planning processes can aid policymakers in developing resilient, ecologically sustainable cities worldwide.

Introduction: Many studies have reported the role of P-glycoprotein (Pgp) in chemoresistance in various pathological conditions such as cancer and neurodegenerative diseases, such as Alzheimer's. In this study, we are reporting the high-performance liquid chromatography (HPLC)-based purification of fluorine-18 [F-18]AVT-011 and its preclinical evaluation. Methods: AVT-011 was labeled with F-18 using the nucleophilic substitution method by heating the reaction mixture at 110 degrees C for 10 min, followed by purification using preparative HPLC and C18ec cartridge. The in vitro cell uptake study was carried out in U87 cells with and without an inhibitor. The preclinical toxicity was carried out in CD1 mice in three groups, including control, AVT-011 treated, and [F-18]AVT-011 treated. The biodistribution study was done in CD1 mice (n = 12) after intravenous injection of 4-6 MBq [F-18]AVT-011, and mice were sacrificed at various time intervals. A dose of 3.7 +/- 0.7 MBq of [F-18]AVT-011 was injected intravenously in the healthy Swiss albino mice, and the whole-body micro-positron emission tomography was acquired at 0-, 30-, 60-, and 120-min postinjection. Results: The radiochemical purity of [F-18]AVT-011 was 97 +/- 1.5% as evaluated by radio-HPLC with a yield of 14 +/- 2% and was stable up to 95% under in vitro conditions in blood and in vivo conditions up to 4 h. The in vitro cell uptake study showed a significant difference in control (27.4 +/- 2.1%) and blocked U987 cells (73.2 +/- 3.2%) after incubation of 120 min. The tissue distribution in mice showed the highest uptake in the liver (17.3 +/- 2.4%), kidneys (16.6 +/- 3.1%), lungs (10.4 +/- 2.9%), and spleen (5.6 +/- 0.8%) at 15 min, and the activity was washed out with time. The radioactivity cleared through the hepatorenal pathway. The animal imaging study also demonstrates a similar biodistribution pattern. Conclusions: [F-18]AVT-011 showed higher specific activity than the cartridge-based method but showed similar biological activity.

Background: Parkinson’s disease (PD) is characterized by the degeneration of dopaminergic neurons in the substantia nigra. SPECT imaging using technetium-99m [99mTc] labeled trodat is the choice of imaging to differentiate PD from its other forms like drug-induced PD. Aims and Objectives: The main objective of our study was to prepare in-house sterile formulation of [99mTc]Tc-trodat and use in clinics. Materials and Methods: The labeling of trodat was standardized using glucoheptonate sodium salt (GHA), stannous chloride dihydrate (in 0.05 N HCl), and ethylenediaminetetraacetic acid (Na-EDTA). The preparation was mixed and autoclaved at 15 psi for 15 min. The standardised formulation was stored at 4°C, -20°C and -80°C and labeling with 99mTc was tested for up to 6 days. The radiochemical purity, chemical impurities, and endotoxin levels were tested. The frozen formulation was tested in swiss mice (n = 3) for biodistribution studies at 4 h. Around 18 ± 2 mCi was injected intravenously in each patient (n = 5) and the image was acquired at 4 h post-injection. Results: The radiochemical purity of the preparation was 98.3 ± 1.4% with a retention time of 16.8 ± 1.5 min as compared to 4.0 ± 0.5 min for free 99mTc. Animal distribution showed highest uptake in liver and dual excretion via hepatobiliary and renal system. [99mTc]Tc-trodat imaging was able to differentiate both caudate and putamen. Conclusions: In-house frozen preparation was advantageous, as it has decreased the chance of manual error as compared to daily make up formulations and economical as compared to commercially available kits.

BackgroundUnderstanding the patterns and processes of species distributions has long remained a central focus of biogeographical and ecological research. While the evidence for elevational patterns in species richness is widespread, our understanding of underlying causes and mechanisms remains limited. Therefore, this study aimed to entangle the influence of environmental variables on plant species richness along elevational gradients in the Western Himalayas.MethodsWe compiled elevational distribution for about 1150 vascular plants using the published literature and available database. The species richness was estimated in 100-m elevational bands using the range interpolation method. We used the generalised linear model and structural equation modelling (SEM) framework to identify the direct and indirect effects of climatic factors on species richness.ResultsOur results indicated that primary environmental correlates of species richness varied with elevational gradients. Climatic variables combined with energy and water availability were more important than the topographic heterogeneity. Further, the direct and interaction effects of climatic variables were more substantial than their indirect effects. The indirect effects of climate are more strongly mediated by water-energy dynamics than the energy alone.ConclusionsOverall, our findings emphasise the importance of considering direct effects and interactions among environmental variables while studying the underlying mechanisms governing elevational biodiversity gradients. Species richness appeared to be shaped by climatic tolerances rather than habitat heterogeneity at regional scales. This information can have implications for biodiversity dynamics under environmental change.

INTRODUCTION:Antibiotic resistance is a burden on the healthcare system. In present study, we have labeled an antibiotic named Colistimethate sodium (CMS) with technetium-99m (99mTc) to develop a SPECT based imaging tracer. METHODS:We standardised the labeling using 0.5-2 mg of CMS (in water) using stannous chloride dihydrate as a reducing agent followed by addition of 370 ± 74 MBq of 99mTc. A group of mice were injected intravenously (in tail vein) with 4-6 MBq of [99mTc]Tc-CMS diluted with saline and euthanized at various time intervals. microSPECT Imaging (ϒ-eye) was acquired to study the biodistribution in the healthy mice. RESULTS:We standardised the labeling using 0.5 mg of colistin in 0.5 ml of saline with addition of 30 μg stannous chloride dihydrate. The retention factor value was 0.1-0.3 as compared to 0.9-1.0 for free 99mTc by TLC and retention time was found to be 14.2 ± 1.3 min as evaluated by HPLC. The biodistribution data showed uptake in lungs, spleen, and liver at 30 min but the uptake decreased in lung at 60 min. The imaging data corroborated with the biodistribution data. CONCLUSIONS:We could successfully label [99mTc]Tc-CMS 99mTc and we could study its biodistribution in healthy mice.

11C-labelled L-methionine is a promising radiotracer for detecting brain tumors. In this study, we have devised a novel approach for [11C]methionine radiosynthesis and observed its impact on the final radiochemical yield. We found an increase of 20

Background:Differentiation between recurrence of brain tumor and radiation necrosis remains a challenge in current neuro-oncology practice despite recent advances in both radiological and nuclear medicine techniques.Purpose:The purpose of this study was to compare the diagnostic performance of dynamic susceptibility contrast (DSC) perfusion magnetic resonance imaging (MRI), apparent diffusion coefficient (ADC) derived from diffusion-weighted imaging, and F18-fluorodeoxyglucose-positron emission tomography (F18-FDG-PET) in the differentiation between the recurrence of a high-grade glioma and radiation necrosis.Materials and Methods:Patients with a diagnosis of high-grade glioma (WHO Grades III and IV) who had undergone surgical resection of the tumor followed by radiotherapy with or without chemotherapy were included in the study. DSC perfusion, diffusion-weighted MRI, and PET scan were acquired on a hybrid PET/MRI scanner. For each lesion, early and delayed tumor-to-brain ratio (TBR), early and delayed maximum standardized uptake value (SUVmax), normalized ADC ratio, and normalized relative cerebral blood volume (rCBV) ratio were calculated and the pattern of lesional enhancement was noted. The diagnosis was finalized with either histopathological examination or the characteristics on follow-up imaging. The statistical analysis using the receiver operator characteristic curves was done to determine the diagnostic performance of DSC perfusion, 18-F FDG-PET, and ADC in differentiation between tumor recurrence and radiation necrosis.Results:Fifty patients were included in the final analysis, 32 of them being men (64%). A cutoff value of early TBR >0.8 (sensitivity of 100% and specificity of 80%), delayed TBR >0.93 (sensitivity of 92.3% and specificity of 80%), early SUVmax >10.2 (sensitivity of 76.9% and specificity of 80%), delayed SUVmax >13.2 (sensitivity of 61.54% and specificity of 100%), normalized rCBV ratio >1.21 (sensitivity of 100% and specificity of 60%), normalized ADC ratio >1.66 (sensitivity of 38.5% and specificity of 80%), and Grade 3 enhancement (sensitivity of 100% and specificity of 60%) were found to differentiate recurrence from radiation necrosis. Early TBR had the highest accuracy (94.44%), while ADC ratio had the lowest accuracy (50%). A combination of early TBR (cutoff value of 0.8), late TBR (cutoff value of 0.93), and rCBV ratio (cutoff value of 1.21) showed a sensitivity of 100%, specificity of 92.3%, positive predictive value of 88.9%, negative predictive value of 93.7%, and an accuracy of 96.6% in discrimination between radiation necrosis and recurrence of tumor.Conclusion:F18-FDG-PET and DSC perfusion can reliably differentiate tumor recurrence from radiation necrosis, with early TBR showing the highest accuracy. ADC demonstrates a low sensitivity, specificity, and accuracy in differentiating radiation necrosis from recurrence. A combination of early TBR, delayed TBR, and rCBV may be more useful in discrimination between radiation necrosis and recurrence of glioma, with this combination showing a better diagnostic performance than individual parameters or any other combination of parameters.

Positron emission tomography (PET) using O-(2-[18 F]fluoroethyl)-L-tyrosine ([18 F]FET) has shown great success in differentiating tumor recurrence from necrosis. In this study, we are reporting the experience of synthesis [18 F]FET by varying the concentration of TET precursor in different chemistry modules. TET precursor (2-10 mg) was used for the synthesis of [18 F]FET in an automated (MX Tracerlab) module (n = 6) and semiautomated (FX2N Tracerlab) module (n = 19). The quality control was performed for all the preparations. For human imaging, 220 ± 50 MBq of [18 F]FET was briefly injected into the patient to acquire PET-MR images. The radiochemical purity was greater than 95% for the final product in both modules. The decay corrected average yield was 10.7 ± 4.7% (10 mg, n = 3) and 8.2 ± 2.6% (2 mg, n = 3) with automated chemistry module and 36.7 ± 7.3% (8-10 mg, n = 12), 26.4 ± 3.1% (5-7 mg, n = 4), and 35.1 ± 3.8% (2-4 mg, n = 3) with semiautomated chemistry modules. The PET imaging showed uptake at the lesion site (SUVmax  = 7.5 ± 2.6) and concordance with the MR image. The [18 F]FET was produced with a higher radiochemical yield with 2.0 mg of the precursor with substantial yield and is suitable for brain tumor imaging.

India is one of the global economies where the energy sector is primarily coal driven and ranks third in coal production after China and the USA. About seventy percent coal extraction in India is operated through open-cast mining, which is more devastating for vegetation and topsoil. As a result, the stored C in the soil is released back to the atmosphere and potentially contributes to global warming. Mine soils are pedogenically young soils but pedobiologically no sense, which is deprived of organic matter, acidic in nature, lack essential soil nutrients, thus, unable to support plant growth at initial state. However, ecological techniques for revegetation and proper soil management practices may augment soil organic matter accumulation and ecosystem development. In India, mine soils after revegetation are reported to sequester 3.64 t C ha−1 year−1. Reclaimed mine soils in the USA are estimated to offset 30 tera grams (Tg) of CO2 each year. Amendment of mine spoils by using organic wastes such as biosolids, manures, mulches, and biochar is influential application in alleviating soil's physical, chemical, and biological properties. However, further studies are warranted to understand the positive and negative aspects of organic soil amendment, because minesoil management accelerates ecosystem recovery and enhances sink size for the rising level of atmospheric CO2 in a changing environment.