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Abstract Background Lung cancer remains a leading cancer type, but current chemotherapy is limited by issues including poor drug delivery, toxicity, and resistance. To address these challenges, we developed a novel PLGA-PEG-LHRH (PPL) nanoconjugate system for improved drug delivery. Curcumin, known for its anticancer and P-gp inhibition properties, was co-loaded with bcl2siRNA (bclsR) to inhibit the bcl2 protein, thus overcoming both resistance mechanisms. Results The PPL conjugate was successfully synthesized and characterized using FTIR, 1H NMR, XRD, XPS and BCA assay. Curcumin and bclsR-loaded PLGA nanoemulsions were prepared by double emulsion solvent evaporation method and characterized. The optimized nanoconjugate had size of 179 ± 16 nm, favorable zeta potential, high drug entrapment, and was confirmed via TEM. Controlled release studies indicated 83% drug release within 24 h. In vitro studies revealed significant cytotoxicity against A549 lung cancer cells, with the nanoconjugate showing IC50 of 8.24 µg/mL compared to 21.26 µg/mL for plain curcumin. Enhanced cellular uptake and effective targeting of A549 cells were observed. Molecular analyses demonstrated significant downregulation of MDR1 and Bcl2 RNA and protein expression, highlighting the nanoconjugates' ability to suppress resistance mechanisms. Pharmacokinetic studies in Wistar rats showed superior plasma drug concentrations, half-life, and AUC for the nanoconjugate versus pure drug suspension. Biodistribution studies showed increased drug accumulation in the lungs. In vivo efficacy studies in Balb/c mice demonstrated higher tumor inhibition ratios for CUR-siRNA PPL NPs (66.89%) and CUR-PPL NPs (59.84%) which was further confirmed with TNFα and p53 levels in blood. Histopathological studies showed good healing in the CUR-siRNA PPL NP- and CUR-PPL NP-treated mice compared to suspension. Conclusion From the study, it may be concluded that the PPL nanoconjugate system, loaded with curcumin and bcsR, can be potentially effective, multifunctional targeted approach for lung cancer therapy. Graphical Abstract

North Eastern Region (NER) of India comprising of eight states considered to be most unique and one of the most challenging regions to govern due to its unique physiographic condition, rich biodiversity, disaster prone and diverse socio-economic characteristics. Operational Remote Sensing services increased manifolds in the region with the establishment of North Eastern Space Applications Centre (NESAC) in the year 2000. Since inception, NESAC has been providing remote sensing services in generating inventory, planning and developmental activities, and management of natural resources, disasters and dissemination of information and services through geo-web services for NER. The operational remote sensing services provided by NESAC can be broadly divided into three categories viz. natural resource planning and developmental services, disaster risk reduction and early warning services and information dissemination through geo-portal services. As a apart of natural resources planning and developmental services NESAC supports the state forest departments in preparing the forest working plans by providing geospatial inputs covering entire NER, identifying the suitable culturable wastelands for cultivation of silkworm food plants, mapping of natural resources such as land use/land cover, wastelands, land degradation etc. on temporal basis. In the area of disaster risk reduction, NESAC has initiated operational services for early warning and post disaster assessment inputs for flood early warning system (FLEWS) using satellite remote sensing, numerical weather prediction, hydrological modeling etc.; forest fire alert system with actionable attribute information; Japanese Encephalitis Early Warning System (JEWS) based on mosquito vector abundance, pig population and historical disease intensity and agriculture drought monitoring for the region. The large volumes of geo-spatial databases generated as part of operational services are made available to the administrators and local government bodies for better management, preparing prospective planning, and sustainable use of available resources. The knowledge dissemination is being done through online web portals wherever the internet access is available and as well as offline space based information kiosks, where the internet access is not available or having limited bandwidth availability. This paper presents a systematic and comprehensive study on the remote sensing services operational in NER of India for natural resources management, disaster risk reduction and dissemination of information and services, in addition to outlining future areas and direction of space applications for the region.

Background and Aims: There is limited data on the effects of norepinephrine on neonatal outcomes and maternal complications relative to other vasopressors. The study aimed to compare neonatal outcomes and maternal complications after bolus intravenous doses of phenylephrine and norepinephrine for post-spinal hypotension in elective caesarean section women. Methods: This randomised study was done on 100 elective caesarean section women under spinal anaesthesia. Block randomisation divided women into two groups to receive intravenous phenylephrine 50 μg bolus (Group A) or norepinephrine 5 μg bolus (Group B) following post-spinal hypotension. Groups were evaluated and compared for umbilical arterial blood gas analysis, birth weight, APGAR (appearance, pulse, grimace, activity, and respiration) score, maternal haemodynamics, and complications. Kolmogorov-Smirnov and Shapiro-Wilk tests were used to verify data normality. Independent samples t-test or Mann-Whitney U test was employed to compare continuous variables based on data normality, and the Chi-square test was used to determine categorical variable associations. Results: Demographic characteristics of women were found to be comparable between groups. Umbilical arterial potential of hydrogen, partial pressure of oxygen, partial pressure of carbon dioxide, base excess, bicarbonate, birth weight, and APGAR scores were comparable across groups, showing no significant differences (P > 0.05). Groups had similar maternal haemodynamic characteristics and episodes of nausea, vomiting, and chest pain across groups without statistical significance (P > 0.05). Conclusion: No notable distinction was found between neonatal outcomes and maternal complications between phenylephrine and norepinephrine bolus regimens. Norepinephrine can be used as an alternative to phenylephrine post-spinal hypotension in women undergoing elective caesarean section. Keywords: APGAR score, caesarean section, hypotension, norepinephrine, phenylephrine, pregnancy, spinal anaesthesia, umbilical arterial blood gas analysis, Author(s): Prerona Saha (corresponding author) [1]; Chandita Konwar [1]; Aditya Pandey [2]; Prabal Bharali [3] INTRODUCTION Phenylephrine has been identified as a potential vasopressor that has been preferred for the [...]

Abstract Background Carbon dots (CDs) derived from Citrus aurantifolia represent a promising platform for advanced cancer therapy and diagnostics (theranostics). These CDs are synthesized through a sustainable and cost-effective hydrothermal method, utilizing fruit juice as a green carbon source. Despite the potential, research on the synthesis of citrus-based CDs, especially regarding their red fluorescence emission, which is crucial for enhanced tissue penetration and biomedical efficacy, remains limited. Results In this study, CDs were successfully synthesized from C. aurantifolia fruit, yielding nanoparticles below 5 nm in size (PDI 0.231 ± 0.04). Characterization revealed favorable optical properties, including excitation-dependent fluorescent behavior with prominent red emission under higher excitation wavelengths, a quantum yield of 8.17%, and stable photoluminescence. Chemical composition analysis using XPS, FTIR, and XRD confirmed the purity and structure of the CDs. To explore their biomedical application, CDs were co-loaded with curcumin into liposomes. The formulations had a mean size of 177.2 ± 3.6 nm (PDI 0.270 ± 0.012), demonstrated efficient drug entrapment (60.32 ± 2.24%), and exhibited rapid release kinetics, with 90.21 ± 2.16% of the drug release within 8 h. In vitro studies using A549 lung cancer cells demonstrated superior cellular uptake and cytotoxicity of Cur-CD-loaded liposomes compared to curcumin alone (Cur-Suspension), achieving IC50 values of 0.093 ± 0.011 µg/ml and 0.016 ± 0.006 µg/ml, respectively. Conclusion This research underscores C. aurantifolia as a viable natural source for green CD synthesis. The obtained CDs with red fluorescence emission, optimized through reaction conditions and excitation wavelengths, hold promise for enhanced biological applications, particularly in the realm of lung cancer therapy. The findings advocate for further exploration and refinement of citrus-based CDs as versatile theranostic agents, capitalizing on their sustainable origins and potent biomedical properties. The combination of citrus-derived CDs with curcumin loaded into liposomal formulations represents a potent theranostic strategy for lung cancer treatment, leveraging the unique properties of CDs and their potential for targeted and effective therapy. Graphical abstract

IntroductionWastewater-based surveillance (WBS) is an emerging tool for monitoring the spread of infectious diseases, such as SARS-CoV-2, in community settings. Environmental factors, including water quality parameters and seasonal variations, may influence the prevalence of viral particles in wastewater. This study aims to explore the relationships between these factors and the incidence of SARS-CoV-2 across 28 monitoring sites, spanning different seasons and water strata.MethodsSamples were collected from 28 sites, accounting for seasonal and spatial (surface and intermediate water layers) variations. Key physicochemical parameters, heavy metals, and minerals were measured, and viral presence was detected using RT-qPCR. After data preprocessing, correlation analyses identified 19 relevant environmental parameters. Unsupervised learning algorithms, including K-means and K-medoid clustering, were employed to categorize the data into four distinct clusters, revealing patterns of viral positivity and environmental conditions.ResultsCluster analysis indicated that seasonal variations and water quality characteristics significantly influenced SARS-CoV-2 positivity rates. The four clusters demonstrated distinct associations between environmental factors and viral prevalence, with certain clusters correlating with higher viral loads in specific seasons. The clustering patterns varied across sample sites, reflecting the diverse environmental conditions and their influence on viral detection.DiscussionThe findings underscore the critical role of environmental factors, such as water quality and seasonality, in shaping the dynamics of SARS-CoV-2 prevalence in wastewater. These insights provide a deeper understanding of the complex interplay between environmental contexts and disease spread. By utilizing WBS and advanced data analysis techniques, this study offers a robust framework for future research aimed at enhancing public health surveillance and interventions.

Winter fog and severe aerosol loading in the boundary layer over northern India, particularly in the Indo-Gangetic Plain (IGP), disrupt the daily lives of millions of people in the region. To better understand the role of aerosol–radiation (AR) feedback on the occurrence, spatial extent, and persistence of winter fog, as well as the associated aqueous chemistry in fog in the IGP, several model simulations have been performed using the Weather Research and Forecasting model coupled with Chemistry (WRF-Chem). While WRF-Chem was able to represent the fog formation for the 23–24 December 2017 fog event over the central IGP in comparison to station and satellite observations, the model underestimated PM2.5 concentrations compared to the Central Pollution Control Board (CPCB) of India monitoring network. While evaluating aerosol composition for fog events in the IGP, we found that the WRF-Chem aerosol composition was quite different from measurements obtained during the Winter Fog Experiment (WiFEX) in Delhi, with secondary aerosols, particularly the chloride aerosol fraction, being strongly underpredicted (∼ 66.6 %). Missing emission sources (e.g., industry and residential burning of cow dung and trash) and aerosol and chemistry processes need to be investigated to improve model–observation agreement. By investigating a fog event on 23–24 December 2017 over the central IGP, we found that the aerosol–radiation feedback weakens turbulence, lowers the boundary layer height, and increases PM2.5 concentrations and relative humidity (RH) within the boundary layer. Factors affecting the feedback include loss of aerosols through deposition of cloud droplets and internal mixing of absorbing and scattering aerosols. Aqueous-phase chemistry increases the PM2.5 concentrations, which subsequently affect the aerosol–radiation feedback by both increased mass concentrations and aerosol sizes. With aerosol–radiation interaction and aqueous-phase chemistry, fog formation began 1–2 h earlier and caused a longer fog duration than when these processes were not included in the WRF-Chem simulation. The increase in RH in both experiments was found to be important for fog formation as it promoted the growth of aerosol size through water uptake, increasing the fog water content over the IGP. The results from this study suggest that the aerosol–radiation feedback and secondary aerosol formation play an important role in the air quality and the intensity and lifetime of fog over the IGP, yet other feedbacks, such as aerosol–cloud interactions, need to be quantified.