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Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small-cell lung cancer (NSCLC) is the most common type accounting for 84% of all lung cancers. Paclitaxel (PAC) is a widely used drug in the treatment of a broad spectrum of human cancers, including lung. While efficacious, PAC generally is not well tolerated and its limitations include low aqueous solubility, and significant toxicity. To overcome the dose-related toxicity of solvent-based PAC, we utilized bovine colostrum-derived exosomes as a delivery vehicle for PAC for the treatment of lung cancer. Colostrum provided higher yield of exosomes and could be loaded with higher amount of PAC compared to mature milk. Exosomal formulation of PAC (ExoPAC) showed higher antiproliferative activity and inhibition of colony formation against A549 cells compared with PAC alone, and also showed antiproliferative activity against a drug-resistant variant of A549. To further enhance its efficacy, exosomes were attached with a tumor-targeting ligand, folic acid (FA). FA-ExoPAC given orally showed significant inhibition (>50%) of subcutaneous tumor xenograft while similar doses of PAC showed insignificant inhibition. In the orthotopic lung cancer model, oral dosing of FA-ExoPAC achieved greater efficacy (55% growth inhibition) than traditional i.v. PAC (24–32% growth inhibition) and similar efficacy as i.v. Abraxane (59% growth inhibition). The FA-ExoPAC given i.v. exceeded the therapeutic efficacy of Abraxane (76% growth inhibition). Finally, wild-type animals treated with p.o. ExoPAC did not show gross, systemic or immunotoxicity. Solvent-based PAC caused immunotoxicity which was either reduced or completely mitigated by its exosomal formulations. These studies show that a tumor-targeted oral formulation of PAC (FA-ExoPAC) significantly improved the overall efficacy and safety profile while providing a user-friendly, cost-effective alternative to bolus i.v. PAC and i.v. Abraxane.

This study investigated the human risk of infection due to inadvertent ingestion of water during swimming in a river that receives SARS-CoV-2-containing effluent from a wastewater treatment plant (WWTP). A quantitative microbial risk assessment (QMRA) approach was applied for risk estimation using dose-response models (DRM) of different surrogate coronaviruses (SARS-CoV-1, MERS-CoV) and the virus responsible for most infectious respiratory illnesses (i.e., influenza A H5N1) due to the unavailability of DRM for SARS-CoV-2. The ratio of infectious concentration to genomic copies of SARS-CoV-2 is unknown and also unavailable for other coronaviruses. Therefore, literature-based information on enteric viruses was used for formulating the ratio used for QMRA, although it is acknowledged that identifying this information for SARS-CoV-2 is a priority, and in the absence of information specific to SARS-CoV-2, another coronavirus would be a preferable surrogate to the enteric viruses used here. The calculated concentration of ingested SARS-CoV-2 ranged between 4.6 × 10 − 7 and 80.5 genomic copies/dip (one swim = 32 mL). The risk of infection (> 9 × 10 − 12 to 5.8 × 10 − 1 ) was found to be > 1/10,000 annual risk of infection. Moreover, the study revealed that the risk estimation was largely dependent on the value of the molecular concentration of SARS-CoV-2 (gc/mL). Overall immediate attention is required for obtaining information on the (i) ratio of infectious virus to genomic copies, (ii) DRM for SARS-CoV-2, and (iii) virus reduction rate after treatment in the WWTPs. The QMRA structure used in present findings is helpful in analyzing and prioritizing upcoming health risks due to swimming performed in contaminated rivers during the COVID-19 outbreak. Graphical abstract

This study aimed to assess heavy metals in the surface sediments of the Bharalu river, India. Metal concentrations ranged from 6.65−54.6 mg/kg for Ni, 25.2−250.0 mg/kg for Zn, 83.3−139.1 mg/kg for Pb, and 11940.0−31250.0 mg/kg for Fe. The level of metal contamination was assessed using sediment quality guidelines, geo-accumulation index (I geo ), enrichment factor (EF), pollution Load Index (PLI),Nemerow’s pollution index (PIN), and potential ecological risk index. Pb exceeded the sediment quality guidelines at all sites indicating a potential threat to the river ecosystem. (I geo ) and EF also showed moderate to severe enrichment for Pb. Potential ecological risk (RI) showed low risk in the sediments, and Pb is the major contributor to ecological risk. Overall, pollution indices revealed comparably higher contamination of the sediments in the downstream sites than in the upstream site. PCA and correlation matrix analysis indicated both anthropogenic and natural origins for metals. Among anthropogenic sources, urban discharges and waste dumping could be mainly attributed to metal contamination in the river sediments. These findings may aid in developing future river management methods explicitly aimed at tackling heavy metal pollution to prevent further damage to the river ecosystem.

Swarm Intelligence (SI) has become a strong paradigm for numerical optimization, which has inspired a wide range of metaheuristic algorithms. This paper presents the Hybrid Mating Optimization (HMO), a novel bio-inspired algorithm that synergically merges four mating and communication behaviors of nature: butterfly pheromone navigation (global exploration), honeybee foraging (local exploitation), red deer dominance selection (adaptive hierarchy), and woodpecker rhythmic perturbation (diversity preservation). This hybrid mechanism is able to find a dynamic balance between exploration and exploitation, without causing premature convergence. Extensive experiments on the CEC-2017 benchmark suite show that HMO can converge faster and obtain higher accuracy than state-of-the-art algorithms such as PSO, DE, EHO, and CMA-ES. The statistical significance is further verified using Wilcoxon signed-rank tests and t-tests. HMO also has scalability both in unimodal and multimodal environments. Furthermore, a real-world case study of an engineering problem on pressure vessel design validates the effectiveness of HMO in constrained optimization problems.

In the emerging field of nanomedicine, nanoparticles have been widely considered as drug carriers and are now used in various clinically approved products. Therefore, in this study, we synthesized superparamagnetic iron-oxide nanoparticles (SPIONs) via green chemistry, and the SPIONs were further coated with tamoxifen-conjugated bovine serum albumin (BSA-SPIONs-TMX). The BSA-SPIONs-TMX were within the nanometric hydrodynamic size (117 ± 4 nm), with a small poly dispersity index (0.28 ± 0.02) and zeta potential of −30.2 ± 0.09 mV. FTIR, DSC, X-RD, and elemental analysis confirmed that BSA-SPIONs-TMX were successfully prepared. The saturation magnetization (Ms) of BSA-SPIONs-TMX was found to be ~8.31 emu/g, indicating that BSA-SPIONs-TMX possess superparamagnetic properties for theragnostic applications. In addition, BSA-SPIONs-TMX were efficiently internalized into breast cancer cell lines (MCF-7 and T47D) and were effective in reducing cell proliferation of breast cancer cells, with IC50 values of 4.97 ± 0.42 μM and 6.29 ± 0.21 μM in MCF-7 and T47D cells, respectively. Furthermore, an acute toxicity study on rats confirmed that these BSA-SPIONs-TMX are safe for use in drug delivery systems. In conclusion, green synthesized superparamagnetic iron-oxide nanoparticles have the potential to be used as drug delivery carriers and may also have diagnostic applications.

The use of wireless and Internet of Things (IoT) devices is growing rapidly. Because of this expansion, nowadays, mobile apps are integrated into low-cost, low-power platforms. Low-power, inexpensive sensor nodes are used to facilitate this integration. Given that they self-organize, these systems qualify as IoT-based wireless sensor networks. WSNs have gained tremendous popularity in recent years, but they are also subject to security breaches from multiple entities. WSNs pose various challenges, such as the possibility of numerous attacks, their innate power, and their unfeasibility for use in standard security solutions. In this paper, to overcome these issues, we propose the secure encryption random permutation pseudo algorithm (SERPPA) for achieving network security and energy consumption. SERPPA contains a major entity known as a cluster head responsible for backing up and monitoring the activities of the nodes in the network. The proposed work performance is compared with other work based on secure IoT devices. The calculation metrics taken for consideration are energy, overheads, computation cost, and time consumption. The obtained results show that the proposed SERPPA is very significant in comparison to the existing works, such as GKA (Group Key Agreement) and MPKE (Multipath Key Establishment), in terms of data transfer rate, energy consumption and throughput.

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Arsenic decontamination is a major worldwide concern as prolonged exposure to arsenic (>10 µg L -1 ) through drinking water causes serious health hazards in human beings. The selection of significant, cost-effective, and affordable processes for arsenic removal is the need of the hour. For the last decades, iron-oxide nanomaterials (either in the magnetite or bimetallic form) based adsorptive process gained attention owing to their high arsenic removal efficiency and high regenerative capacity as well as low yield of harmful by-products. In the current state-of-the-art, a comprehensive literature review was conducted focused on the applicability of iron-based nanomaterials for arsenic removal by considering three main factors: (a) compilation of arsenic removal efficiency, (b) identifying factors that are majorly affecting the process of arsenic adsorption and needs further investigation, and (c) regeneration capacity of adsorbents without affecting the removal process. The results revealed that magnetite and bimetallic nanomaterials are more effective for removing Arsenic (III) and Arsenic (V). Further, magnetite-based nanomaterials could be used up to five to six reuse cycles, whereas this value varied from three to six reuse cycles for bimetallic ones. However, most of the literature was based on laboratory findings using decided protocols and sophisticated instruments. It cannot be replicated under natural aquatic settings in the occurrence of organic contents, fluctuating pH and temperature, and interfering compounds. The primary rationale behind this study is to provide a comparative picture of arsenic removal through different iron-oxide nanomaterials (last twelve yearsof published literature) and insights into future research directions.

The importance of parental involvement in the care and management decisions made for children hospitalized in the pediatric intensive care unit (PICU) is examined in this editorial. Initial days and weeks in a PICU can be challenging for the child and family due to the emotional intensity and medical complexity of the therapy a child receives. Regardless of the result, families may feel uncertain and anxious that their child may die or have a terrible outcome. The majority of pediatric patient deaths in hospitals happen in the PICU. Recognizing and supporting the crucial role of parents or caretakers in informed decision-making and management of their child's condition is essential for advancing prevention, detection, and treatment efforts.

Glutaric aciduria type 1 (GA1) is an organic aciduria inherited in an autosomal recessive pattern, with an occurrence rate of one in 100,000. It is caused by a deficiency of the enzyme glutaryl-CoA dehydrogenase (GCDH), encoded by the gene on chromosome 19. It is an important enzyme in the catabolism of amino acids such as tryptophan, lysine, and hydroxylysine. Its deficiency leads to the accumulation of organic acids such as glutaric acid and 3-hydroxyglutaric acid, which interfere with cerebral energy metabolism and cause neurological symptoms. Here, we discuss the case of a six-month-old male child who presented with status epilepticus following an eight-day history of fever. The child was started on anti-epileptics. Initially, the child was on non-invasive ventilation and was later intubated and taken on a mechanical ventilator. A magnetic resonance imaging (MRI) scan of the brain was performed, and the findings suggested GA1. The child was started on carnitine after samples were sent for tandem mass spectrometry (TMS) and urine gas chromatography-mass spectrometry (GC/MS), which came out to be positive for GA1. Despite the timely intervention, the child did not survive. Most cases exhibit movement disorders, with many presenting in acute encephalitic crises. Additionally, a significant portion of patients experience an insidious onset of the disease. An MRI of the brain shows widened Sylvian fissures in the majority of cases. Treatment of GA1 includes dietary modifications, including a low-lysine diet and administering carnitine. Early diagnosis and management result in decreased mortality and morbidity, which underscores the need for newborn screening.