Hydrogeochemical characterization and geochemical modeling for the evaluation of groundwater quality and health risk assessment in the Varuna River basin, India.

This study focuses on determining significant controlling factors of chemical consequences, inverse geochemical modeling, water quality, and human health risk in the Varuna River basin of India. The study interprets that according to pH, total dissolved solids, and total hardness, the maximum number of groundwater samples are alkaline, fresh, and have substantial hardness. The abundance of major ions follows a pattern: Na > Ca > Mg > K, and HCO3 > Cl > SO4 > NO3 > F. Piper diagram shows that Ca-Mg-HCO3 facies are predominant during both seasons. Na-normalized molar ratios of HCO3/Na, Mg/Na, and Ca/Na are 0.62, 0.95, and 1.82 (pre-monsoon) and 0.69, 0.91, and 1.71 (post-monsoon), respectively, elucidating the coupled silicate and carbonate weathering (dolomite dissolution) sources. The Na/Cl molar ratio is 5.3 (pre-monsoon) and 3.2 (post-monsoon), indicating silicate alteration as the primary process rather than halite dissolution. The chloro-alkaline indices confirm the presence of reverse ion- exchange. Geochemical modeling using PHREEQC identifies the formation of secondary kaolinite minerals. The inverse geochemical modeling categorizes the groundwaters along the flow path from recharge area waters (Group I: Na-HCO3-Cl), transitional area waters (Group II: Na-Ca-HCO3), and discharge area waters (Group III: Na-Mg-HCO3). The model demonstrates the prepotency of water-rock interactions in pre-monsoon justified by the precipitation of Chalcedony and Ca-montmorillonite. The mixing analysis shows that in the alluvial plains, groundwater mixing is a significant hydrogeochemical process that affects groundwater quality. The Entropy Water Quality Index ranks 45% (pre-monsoon) and 50% (post-monsoon) of samples as an excellent category. However, the non-carcinogenic health risk assessment shows that children are more susceptible to fluoride and nitrate contamination.

Chelators of iron and their role in plant's iron management.

Proper transport of metal and their homeostasis is very crucial for the growth and development of plants. Plants root are the primary organs which comes in contact with the stress and thus few modifications occurs, often determining the nutrient efficiency or sometimes as a stress tolerance mechanism. Plant utilizes two strategies for the uptake of iron viz, strategy I-reduction based and strategy II-chelation based. In this review we attempted for a better understanding of how the chelators acts in the mechanism of iron uptake from soils to plants and how iron is distributed in the plants.

Recent advances in CAR T-cell engineering using synthetic biology: Paving the way for next-generation cancer treatment.

This book chapter highlights a comprehensive exploration of the transformative innovations in the field of cancer immunotherapy. CAR (Chimeric Antigen Receptor) T-cell therapy represents a groundbreaking approach to treat cancer by reprogramming a patient immune cells to recognize and destroy cancer cells. This chapter underscores the critical role of synthetic biology in enhancing the safety and effectiveness of CAR T-cell therapies. It begins by emphasizing the growing importance of personalized medicine in cancer treatment, emphasizing the shift from one-size-fits-all approaches to patient-specific solutions. Synthetic biology, a multidisciplinary field, has been instrumental in customizing CAR T-cell therapies, allowing for fine-tuned precision and minimizing unwanted side effects. The chapter highlights recent advances in gene editing, synthetic gene circuits, and molecular engineering, showcasing how these technologies are optimizing CAR T-cell function. In summary, this book chapter sheds light on the remarkable progress made in the development of CAR T-cell therapies using synthetic biology, providing hope for cancer patients and hinting at a future where highly personalized and effective cancer treatments are the norm.

Extracellular Vesicles in Malaria: Shedding Light on Pathogenic Depths.

Malaria, a life-threatening infectious disease caused by Plasmodium falciparum, remains a significant global health challenge, particularly in tropical and subtropical regions. The epidemiological data for 2021 revealed a staggering toll, with 247 million reported cases and 619,000 fatalities attributed to the disease. This formidable global health challenge continues to perplex researchers seeking a comprehensive understanding of its pathogenesis. Recent investigations have unveiled the pivotal role of extracellular vesicles (EVs) in this intricate landscape. These tiny, membrane-bound vesicles, secreted by diverse cells, emerge as pivotal communicators in malaria's pathogenic orchestra. This Review delves into the multifaceted roles of EVs in malaria pathogenesis, elucidating their impact on disease progression and immune modulation. Insights into EV involvement offer potential therapeutic and diagnostic strategies. Integrating this information identifies targets to mitigate malaria's global impact. Moreover, this Review explores the potential of EVs as diagnostic biomarkers and therapeutic targets in malaria. By deciphering the intricate dialogue facilitated by these vesicles, new avenues for intervention and novel strategies for disease management may emerge.

Unveiling Novel Drug Targets and Emerging Therapies for Rheumatoid Arthritis: A Comprehensive Review.

Rheumatoid arthritis (RA) is a chronic debilitating autoimmune disease, that causes joint damage, deformities, and decreased functionality. In addition, RA can also impact organs like the skin, lungs, eyes, and blood vessels. This autoimmune condition arises when the immune system erroneously targets the joint synovial membrane, resulting in synovitis, pannus formation, and cartilage damage. RA treatment is often holistic, integrating medication, physical therapy, and lifestyle modifications. Its main objective is to achieve remission or low disease activity by utilizing a "treat-to-target" approach that optimizes drug usage and dose adjustments based on clinical response and disease activity markers. The primary RA treatment uses disease-modifying antirheumatic drugs (DMARDs) that help to interrupt the inflammatory process. When there is an inadequate response, a combination of biologicals and DMARDs is recommended. Biological therapies target inflammatory pathways and have shown promising results in managing RA symptoms. Close monitoring for adverse effects and disease progression is critical to ensure optimal treatment outcomes. A deeper understanding of the pathways and mechanisms will allow new treatment strategies that minimize adverse effects and maintain quality of life. This review discusses the potential targets that can be used for designing and implementing precision medicine in RA treatment, spotlighting the latest breakthroughs in biologics, JAK inhibitors, IL-6 receptor antagonists, TNF blockers, and disease-modifying noncoding RNAs.

Investigation of Host-Guest Inclusion Complex of Mephenesin with α-Cyclodextrin for Innovative Application in Biological System.

The goal of this study was to use coevaporation to look into how polyether compounds like mephenesin (MEP) can be encapsulated into the host molecule α-cyclodextrin's nanohydrophobic cage. Fourier transform infrared spectroscopy (FT-IR) investigations, powder X-ray diffraction (PXRD), and 1H NMR were among the spectroscopic techniques used to describe the inclusion complex. Additionally, Job's plot has been utilized to illustrate how MEP is encapsulated with α-cyclodextrin (α-CD) at a 1:1 molar ratio. The thermal stability of MEP increased after encapsulation according to thermogravimetric analysis (TGA) and differential thermal analysis (DTA) experiments. Mephenesin fits into the cavity of α-cyclodextrin in a 1:1 ratio, as observed by molecular docking for the inclusion complex to find the most appropriate orientation. This observation is further supported by the Job plot. Furthermore, a comparison was carried out based on a cell viability study between the medication and its inclusion complex.

Transcriptomic Analysis Revealed Reactive Oxygen Species Scavenging Mechanisms Associated With Ferrous Iron Toxicity in Aromatic Keteki Joha Rice.

Lowland acidic soils with water-logged regions are often affected by ferrous iron (Fe2+) toxicity, a major yield-limiting factor of rice production. Under severe Fe2+ toxicity, reactive oxygen species (ROS) are crucial, although molecular mechanisms and associated ROS homeostasis genes are still unknown. In this study, a comparative RNA-Seq based transcriptome analysis was conducted to understand the Fe2+ toxicity tolerance mechanism in aromatic Keteki Joha. About 69 Fe homeostasis related genes and their homologs were identified, where most of the genes were downregulated. Under severe Fe2+ toxicity, the biosynthesis of amino acids, RNA degradation, and glutathione metabolism were induced, whereas phenylpropanoid biosynthesis, photosynthesis, and fatty acid elongation were inhibited. The mitochondrial iron transporter (OsMIT), vacuolar iron transporter 2 (OsVIT2), ferritin (OsFER), vacuolar mugineic acid transporter (OsVMT), phenolic efflux zero1 (OsPEZ1), root meander curling (OsRMC), and nicotianamine synthase (OsNAS3) were upregulated in different tissues, suggesting the importance of Fe retention and sequestration for detoxification. However, several antioxidants, ROS scavenging genes and abiotic stress-responsive transcription factors indicate ROS homeostasis as one of the most important defense mechanisms under severe Fe2+ toxicity. Catalase (CAT), glutathione (GSH), ascorbate peroxidase (APX), monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR), and glutathione reductase (GR) were upregulated. Moreover, abiotic stress-responsive transcription factors, no apical meristem (NAC), myeloblastosis (MYB), auxin response factor (ARF), basic helix-loop-helix (bZIP), WRKY, and C2H2-zinc finger protein (C2H2-ZFP) were also upregulated. Accordingly, ROS homeostasis has been proposed as an essential defense mechanism under such conditions. Thus, the current study may enrich the understanding of Fe-homeostasis in rice.

Physio-biochemical and molecular assessment of Iron (Fe2+) toxicity responses in contrasting indigenous aromatic Joha rice cultivars of Assam, India.

Iron (Fe) toxicity is one of the major abiotic stresses which limits the yield of lowland rice. This study aims to investigate the physiological, biochemical, and molecular aspects of two contrasting aromatic Joha rice, viz., Keteki and Kola Joha of Assam. Oxidative damage caused due to Fe2+ toxicity was quantitatively determined. Fe2+ toxicity in the growth medium increases the level of ROS and anti-oxidative enzyme activity. Along with the aforementioned damage caused due to Fe2+ toxicity, chlorophyll content decreases in both the rice varieties. Detection of Fe3+ and Fe2+ was also conducted by Perls' Prussian and Turnbull blue method, respectively. In addition, spectrophotometric quantification of Fe2+ was determined by 2, 2'-Bipyridyl (Bpy). Above 2.5 mM, Fe2+ toxicity was found to be lethal in rice seedlings affecting their total growth and biomass. Gene expression analysis of iron-regulated transporter 1 (OsIRT1), Yellow Stripe-Like 15 (OsYSL15), and ferritin 1 (OsFer1) revealed the differential gene expression over a time period of Fe2+ toxicity. Our study suggested that the different parameters which are considered here can be helpful for the better understanding of how aromatic Joha rice performed under Fe2+ toxicity which can also help to reveal broader aspects that how gene players are involved in the iron homeostasis mechanism in Joha rice in coming future.