A comprehensive in silico analysis of putative outer membrane and secretory hydrolases from the pathogenic Leptospira: Possible implications in pathogenesis.

Outer surface/membrane and virulent secretory proteins are primarily crucial for pathogenesis. Secreted and outer membrane hydrolases of many pathogens play an important role in attenuating the host immune system. Leptospira expresses many such proteins, and few have been characterized to display various roles, including host immune evasion. However, identification, classification, characterization, and elucidation of the possible role of Leptospira's outer membrane and secretory hydrolases have yet to be explored. In the present study, we used bioinformatics tools to predict exported proteins from the pathogenic Leptospira proteome. Moreover, we focused on secretory and outer membrane putative hydrolases from the exported proteins to generate a deeper understanding. Our analysis yielded four putative outer/secretory hydrolases, LIC_10995, LIC_11183, LIC_11463, and LIC_12988, containing α/ß hydrolase fold and displayed similarity with lipase motif. Moreover, their conservation analysis of the predicted hydrolases across the spectrum of different Leptospira species showed high clustering with the pathogenic species. Outer membrane and secretory proteins with lipolytic activity may have a role in pathogenesis. This is the first bioinformatics analysis of secretory and outer membrane α/ß hydrolases from leptospiral species. However, experimental studies are indeed required to unravel this possibility.

Trade-off analysis between gm/ID and fT of GNR-FETs with single-gate and double-gate device structure.

This study examines the operational parameters of field-effect transistors (FETs) using single-gate (SG) and double-gate (DG) graphene nanoribbons (GNRs) within the analog/RF domain. A detailed exploration is conducted through an atomistic pz orbital model, derived from the Hamiltonian of graphene nanoribbons, employing the nonequilibrium Green's function formalism (NEGF) for analysis. The atomic characteristics of the GNRFETs channel are accurately described by utilizing a tight-binding Hamiltonian with an atomistic pz orbital basis set. The primary focus of the analysis revolves around essential analog/RF parameters such as transconductance, transconductance generation factor (TGF), output resistance, early voltage, intrinsic gain, gate capacitance, cut-off frequency, and transit time. Furthermore, the study assesses the gain frequency product (GFP), transfer frequency product (TFP), and gain transfer frequency product (GTFP) to evaluate the balance between transistor efficiency, gain, and cut-off frequency. The research outcomes indicate that double-gate GNRFETs exhibit superior analog/RF performance in comparison to their single-gate counterparts. However, both types of devices demonstrate cut-off frequencies in the gigahertz range. The extensive data presented in this study provides valuable insights into the characteristics of SG and DG GNRFETs, particularly in terms of the figure-of-merit (FoM) for analog/RF performance, offering a comprehensive analysis of the trade-offs in analog applications. In addition, the analysis has been extended be performing a high-performance hybrid 6T static random-access memory (SRAM) to get the impact in their circuit level variation as well as improvement in their circuit performance.

Estimation of Ultrasonic Velocity, Density, Internal Pressure, and Thermophysical Parameters of Ionic Liquid Mixtures: Application of Flory's Statistical Theory.

Flory's statistical theory (FST) has been employed to estimate the ultrasonic velocity, density, internal pressure, and several important thermophysical parameters such as the energy of vaporization, the heat of vaporization, cohesive energy density, polarity index, and solubility for eight binary mixtures of ionic liquids and water within the temperature range of 288.15 to 308.15 K. The ionic liquids chosen for this investigation are [BMim][dca], [BMim][TfO], [BMpy][TfO], [BMpyr][dca], [BMpyr][TfO], [EEPy][ESO4], [HMim][dca], and [MPy][MSO4]. The predicted values of ultrasonic velocity and density show good agreement with the data reported in the literature. It endorses the applicability of FST to these binary mixtures. A comparative analysis of the internal pressure values (Pi) determined by using FST and the standard thermodynamic approach is also presented. The results obtained for Pi using both approaches show good agreement. Besides, for the mixtures under study, the correlation between ultrasonic velocity, density, and surface tension has also been examined. The variation of thermophysical parameters with concentration and temperature changes has been utilized to explore the nature and strength of the solute-solvent interactions prevalent in these mixtures. It is pointed out that A-A-type interactions dominate over A-B-type interactions in water-rich regions of the mixtures.

Statistical modeling, optimization and characterization of andrographolide loaded emulgel for its therapeutic application on skin cancer through enhancing its skin permeability.

Andrographolide is a natural diterpene lactone with multiple biological effects. In the present study, a total of 11 andrographolide-loaded emulgels (ANG 1- ANG 11) were prepared by emulsification and solvent evaporation method using flaxseed oil and xanthan gum in different ratios, as suggested by the Design-Expert software. A 2-factor-5-level design was employed with different responses including spreadability, extrudability, viscosity, and drug release after 1 h (h) and 24 h. Based on the Design-Expert software response, the optimized emulgel ANG 12 was formulated and evaluated. The 24 h In-vitro drug release was found to be 95.7 % following Higuchi kinetics. Ex-vivo skin retention of 784.78 ug/cm2 was observed during the study. MTT assay performed on Human epidermoid carcinoma (A-431) cells demonstrated cell growth arrest at G0/G1 and G2/M phase after 24 h of ANG 12 treatment (IC50: 11.5 µg/ml). The cellular permeability of ANG-12 was assessed by Fluorescein isothiocyanate (FITC) assay. Compared to untreated cells (0.54 % uptake) the ANG-12 treated cells had shown 87.17 % FITC permeation. The biocompatibility study performed on non-cancerous human dermal fibroblast cells (HDF cells) shows 91.54 % viability after 24 h of the treatment showing the non-toxic nature of ANG-12. Confocal imaging had shown a significant time-dependent increase in in-vivo cellular uptake with enhanced, progressive penetration of the emulgel into the skin. An in-vivo skin irritation study conducted on Swiss albino mice confirmed the safety aspects of the ANG 12. Hence, it can be concluded that nanoemulgel of andrographolide (ANG 12) could be a novel approach to treating skin cancer.

A first comprehensive analysis of Transcribed Ultra Conserved Regions uncovers important regulatory functions of novel non-coding transcripts in gliomas.

Transcribed Ultra-Conserved Regions (TUCRs) represent a severely understudied class of putative non-coding RNAs (ncRNAs) that are 100% conserved across multiple species. We performed the first-ever analysis of TUCRs in glioblastoma (GBM) and low-grade gliomas (LGG). We leveraged large human datasets to identify the genomic locations, chromatin accessibility, transcription, differential expression, correlation with survival, and predicted functions of all 481 TUCRs, and identified TUCRs that are relevant to glioma biology. Of these, we investigated the expression, function, and mechanism of action of the most highly upregulated intergenic TUCR, uc.110, identifying it as a new oncogene. Uc.110 was highly overexpressed in GBM and LGG, where it promoted malignancy and tumor growth. Uc.110 activated the WNT pathway by upregulating the expression of membrane frizzled-related protein (MFRP), by sponging the tumor suppressor microRNA miR-544. This pioneering study shows important roles for TUCRs in gliomas and provides an extensive database and novel methods for future TUCR research.

Phosphatidic acid-dependent recruitment of microtubule motors to spherical supported lipid bilayers for in vitro motility assays.

Motor proteins transport diverse membrane-bound vesicles along microtubules inside cells. How specific lipids, particularly rare lipids, on the membrane recruit and activate motors is poorly understood. To address this, we prepare spherical supported lipid bilayers (SSLBs) consisting of a latex bead enclosed within a membrane of desired lipid composition. SSLBs containing phosphatidic acid recruit dynein when incubated with Dictyostelium fractions but kinesin-1 when incubated with rat brain fractions. These SSLBs allow controlled biophysical investigation of membrane-bound motors along with their regulators at the single-cargo level in vitro. Optical trapping of single SSLBs reveals that motor-specific inhibitors can "lock" a motor to a microtubule, explaining the paradoxical arrest of overall cargo transport by such inhibitors. Increasing their size causes SSLBs to reverse direction more frequently, relevant to how large cargoes may navigate inside cells. These studies are relevant to understand how unidirectional or bidirectional motion of vesicles might be generated.

A Comprehensive Review on the Significance of Cysteine in Various Metabolic Disorders; Particularly CVD, Diabetes, Renal Dysfunction, and Ischemic Stroke.

Metabolic disorders have long been a challenge for medical professionals and are a leading cause of mortality in adults. Diabetes, cardiovascular disorders (CVD), renal dysfunction, and ischemic stroke are the most prevalent ailments contributing to a high mortality rate worldwide. Reactive oxygen species are one of the leading factors that act as a fundamental root cause of metabolic syndrome. All of these disorders have their respective treatments, which, to some degree, sabotage the pathological worsening of the disease and an inevitable death. However, they pose a perilous health hazard to humankind. Cysteine, a functional amino acid shows promise for the prevention and treatment of metabolic disorders, such as CVD, Diabetes mellitus, renal dysfunction, and ischemic stroke. In this review, we explored whether cysteine can eradicate reactive oxygen species and subsequently prevent and treat these diseases.

Protein coupled thionine acetate probed silica nanoparticles: An integrated laser-assisted therapeutic approach for treating cancer.

Herein, we report a multifaceted nanoformulation, developed by binding thionine acetate (TA) in silica matrix to form TA loaded silica nanoparticles (STA Nps), which were characterized using various physicochemical techniques. STA NPs were spherical shaped having size 40-50 nm and exhibited good heating efficiency, improved photostability and singlet oxygen production rate than TA alone. In PDT experiment, the rate of degradation for ABDMA was enhanced from 0.1367 min-1 for TA alone to 0.1774 min-1 for STA Nps, depicting an increase in the reactive oxygen species (ROS) generation ability of STA Nps. Further, the cytotoxicity of STA Nps was investigated by carrying out the biophysical studies with Calf thymus DNA (Ct-DNA) and Human Serum Albumin (HSA). The results indicated that the binding of STA Nps to Ct-DNA causes alterations in the double helix structure of DNA and as a result, STA Nps can impart chemotherapeutic effects via targeting DNA. STA Nps showed good binding affinity with HSA without compromising the structure of HSA, which is important for STA Nps sustainable biodistribution and pharmacokinetics. Based on this study, it is suggested that because of the synergistic effect of chemo and phototherapy, STA Nps can be extensively utilized as potential candidates for treating cancer.

Access denied: CMS' action hurts patients with cancer in rural America.

In 2020, cancer claimed more than 600,000 lives in the US. Cancer is an unyielding public health crisis. Cancer treatments typically involve multidisciplinary approaches, including surgery, radiation therapy, chemotherapy, and oral medications. For patients, especially those in rural areas, obtaining multiple oral medications can be inconvenient. The adoption of delivering cancer medications from medically integrated pharmacies (MIPs) has become popular in recent years. On May 12, 2023, CMS introduced guidelines restricting MIPs from delivering cancer-specific medications by mail or to oncology satellite offices and also requiring patients themselves to pick up the medications in person. This regulatory change has had a devastating impact on patients with cancer in rural and underserved communities, exacerbating existing health care disparities. This commentary explores the negative impacts of the policy change by CMS in rural America.

Recent Advances in the Treatment Strategies of Friedreich's Ataxia: A Review of Potential Drug Candidates and their Underlying Mechanisms.

BACKGROUND: Friedreich's ataxia (FRDA) is a rare hereditary neurodegenerative disorder characterized by progressive ataxia, cardiomyopathy, and diabetes. The disease is caused by a deficiency of frataxin, a mitochondrial protein involved in iron-sulfur cluster synthesis and iron metabolism. OBJECTIVE: This review aims to summarize recent advances in the development of treatment strategies for FRDA, with a focus on potential drug candidates and their mechanisms of action. METHODS: A comprehensive literature search was conducted using various authentic scientific databases to identify studies published in the last decade that investigated potential treatment strategies for FRDA. The search terms used included "Friedreich's ataxia," "treatment," "drug candidates," and "mechanisms of action." RESULTS: To date, only one drug got approval from US-FDA in the year 2023; however, significant developments were achieved in FRDA-related research focusing on diverse therapeutic interventions that could potentially alleviate the symptoms of this disease. Several promising drug candidates have been identified for the treatment of FRDA, which target various aspects of frataxin deficiency and aim to restore frataxin levels, reduce oxidative stress, and improve mitochondrial function. Clinical trials have shown varying degrees of success, with some drugs demonstrating significant improvements in neurological function and quality of life in FRDA patients. CONCLUSION: While there has been significant progress in the development of treatment strategies for FRDA, further research is needed to optimize these approaches and identify the most effective and safe treatment options for patients. The integration of multiple therapeutic strategies may be necessary to achieve the best outcomes in FRDA management.

Dual site reactivity of indole-3-Schiff bases with S/Se/Cl substituted ketenes for stereoselective C-4 substituted indole-ß-lactams, biological evaluations, magic chloro effect and molecular docking studies.

A convenient methodology for C-4 indole-ß-lactam hybrids with chloro, sulphur and seleno substitutions through dual site reactivity of indole-3-Schiff bases towards ketenes has been developed. The reaction proceeded in a stereospecific manner with the exclusive formation of trans-ß-lactams assigned with respect to C3-H and C4-H. The synthesized novel ß-lactams have been characterized with the help of elemental analysis (CHNS) and spectroscopic techniques viz.1H NMR, 13C NMR, DEPT 135, HSQC and IR. The trans configuration was further estabilished based on X-ray crystallographic data. Examination of antibacterial properties unveiled that only derivatives 5a and 5b, featuring chloro substitution, exhibited potent activities, underscoring the emergence of the recently coined term "magic chloro effect". Molecular docking analysis provided additional support for the observed in vitro antibacterial activities of compounds 5a-b.

Acute demyelinating encephalomyelitis in a child with pulmonary tuberculosis.

Tuberculosis is a leading cause of mortality in children worldwide. One of the greatest challenges in its management is the difficulty of diagnosis as the manifestations are non-specific and often mimic other illnesses. Neurological infection occurs in approximately 1% of patients diagnosed with tuberculosis, and usually takes the form of tuberculous meningitis or tuberculoma. An 11-year-old girl who was diagnosed with acute disseminated encephalomyelitis, a rare immunological manifestation of tuberculosis, is presented. She recovered completely after a course of high-dose systemic corticosteroids in addition to anti-tuberculosis treatment. Considering the immense burden of this infectious disease, recognition and understanding of the uncommon manifestations are important to enable appropriate and timely treatment.Abbreviations: ADEM: acute disseminated encephalomyelitis; ATT: anti-tuberculosis therapy; CBNAAT: cartridge-based nucleic acid amplification test; CNS: central nervous system; CSF: cerebrospinal fluid; CT: computed tomography; FLAIR: fluid attenuated inversion recovery; IFN: interferon; MRI: magnetic resonance imaging; MTB: Mycobacterium tuberculosis; TB: tuberculosis; TNF: tumour necrosis factor.

Epigenetic regulations in Mycobacterium tuberculosis infection.

Mycobacterium tuberculosis (Mtb) employs several sophisticated strategies to evade host immunity and facilitate its intracellular survival. One of them is the epigenetic manipulation of host chromatin by three strategies i.e., DNA methylation, histone modifications and miRNA involvement. A host-directed therapeutic can be an attractive approach that targets these host epigenetics or gene regulations and circumvent manipulation of host cell machinery by Mtb. Given the complexity of the nature of intracellular infection by Mtb, there are challenges in identifying the important host proteins, non-coding RNA or the secretory proteins of Mtb itself that directly or indirectly bring upon the epigenetic modifications in the host chromatin. Equally challenging is developing the methods of targeting these epigenetic factors through chemical or non-chemical approaches as host-directed therapeutics. The current review article briefly summarizes several of the epigenetic factors that serve to bring upon potential changes in the host transcriptional machinery and targets the immune system for immunosuppression and disease progression in Mtb infection.

Reaction Pattern and Mechanistic Aspects of Iodine and Iodine-Based Reagents in Selenylation of Aliphatic, Aromatic, and (Hetero)Cyclic Systems.

Organoselenium compounds have been the subject of extensive research since the discovery of the biologically active compound ebselen. Ebselen has recently been found to show activity against the main protease of the virus responsible for COVID-19. Other organoselenium compounds are also well-known for their diverse biological activities, with such compounds exhibiting interesting physical properties relevant to the fields of electronics, materials, and polymer chemistry. In addition, the incorporation of selenium into various organic molecules has garnered significant attention due to the potential of selenium to enhance the biological activity of these molecules, particularly in conjunction with bioactive heterocycles. Iodine and iodine-based reagents play a prominent role in the synthesis of organoselenium compounds, being valued for their cost-effectiveness, non-toxicity, and ease of handling. These reagents efficiently selenylate a broad range of organic substrates, encompassing alkenes, alkynes, and cyclic, aromatic, and heterocyclic molecules. They serve as catalysts, additives, inducers, and oxidizing agents, facilitating the introduction of different functional groups at alternate positions in the molecules, thereby allowing for regioselective and stereoselective approaches. Specific iodine reagents and their combinations can be tailored to follow the desired reaction pathways. Here, we present a comprehensive review of the progress in the selenylation of organic molecules using iodine reagents over the past decade, with a focus on reaction patterns, solvent effects, heating, microwave, and ultrasonic conditions. Detailed discussions on mechanistic aspects, such as electrophilic, nucleophilic, radical, electrochemical, and ring expansion reactions via selenylation, multiselenylation, and difunctionalization, are included. The review also highlights the formation of various cyclic, heterocyclic, and heteroarenes resulting from the in situ generation of selenium intermediates, encompassing cyclic ketones, cyclic ethers, cyclic lactones, selenophenes, chromones, pyrazolines, pyrrolidines, piperidines, indolines, oxazolines, isooxazolines, lactones, dihydrofurans, and isoxazolidines. To enhance the reader's interest, the review is structured into different sections covering the selenylation of aliphatic sp2/sp carbon and cyclic sp2 carbon, and then is further subdivided into various heterocyclic molecules.

A first comprehensive analysis of Transcribed Ultra Conserved Regions uncovers important regulatory functions of novel non-coding transcripts in gliomas.

Transcribed Ultra-Conserved Regions (TUCRs) represent a severely understudied class of putative non-coding RNAs (ncRNAs) that are 100% conserved across multiple species. We performed the first-ever analysis of TUCRs in glioblastoma (GBM) and low-grade gliomas (LGG). We leveraged large human datasets to identify the genomic locations, chromatin accessibility, transcription, differential expression, correlation with survival, and predicted functions of all 481 TUCRs, and identified TUCRs that are relevant to glioma biology. Of these, we investigated the expression, function, and mechanism of action of the most highly upregulated intergenic TUCR, uc.110, identifying it as a new oncogene. Uc.110 was highly overexpressed in GBM and LGG, where it promoted malignancy and tumor growth. Uc.110 activated the WNT pathway by upregulating the expression of membrane frizzled-related protein (MFRP), by sponging the tumor suppressor microRNA miR-544. This pioneering study shows important roles for TUCRs in gliomas and provides an extensive database and novel methods for future TUCR research.

Distinct orchid mycorrhizal fungal communities among co-occurring Vanilla species in Costa Rica: root substrate and population-based segregation.

Despite being the second largest family of flowering plants, orchids represent community structure variation in plant-microbial associations, contributes to niche partitioning in metacommunity assemblages. Yet, mycorrhizal communities and interactions remain unknown for orchids that are highly specialized or even obligated in their associations with their mycorrhizal partners. In this study, we sought to compare orchid mycorrhizal fungal (OMF) communities of three co-occurring hemiepiphytic Vanilla species (V. hartii, V. pompona, and V. trigonocarpa) in tropical forests of Costa Rica by addressing the identity of their OMF communities across species, root types, and populations, using high-throughput sequencing. Sequencing the nuclear ribosomal internal transcribed spacer (nrITS) yielded 299 fungal Operational Taxonomic Units (OTUs) from 193 root samples. We showed distinct segregation in the putative OMF (pOMF) communities of the three coexisting Vanilla hosts. We also found that mycorrhizal communities associated with the rare V. hartii varied among populations. Furthermore, we identified Tulasnellaceae and Ceratobasidiaceae as dominant pOMF families in terrestrial roots of the three Vanilla species. In contrast, the epiphytic roots were mainly dominated by OTUs belonging to the Atractiellales and Serendipitaceae. Furthermore, the pOMF communities differed significantly across populations of the widespread V. trigonocarpa and showed patterns of distance decay in similarity. This is the first report of different pOMF communities detected in roots of wild co-occurring Vanilla species using high-throughput sequencing, which provides evidence that three coexisting Vanilla species and their root types exhibited pOMF niche partitioning, and that the rare and widespread Vanilla hosts displayed diverse mycorrhizal preferences.

Comparative efficacy of family mediated intervention versus early intensive behavioural intervention on symptom domains in children with autism spectrum disorder: A randomized controlled trial.

BACKGROUND: Family Mediated Intervention (FMI) and Early Intensive Behavioural Intervention (EIBI) are found to be standard of care for children with Autism Spectrum Disorder (ASD). Comparison of their efficacy were assessed using ISAA as primary outcome measure. METHODS: This study was a parallel arm, open label, randomized active- controlled non-inferiority clinical trial. 50 Children diagnosed with ASD were randomized into FMI and EIBI groups. Clinical status was checked by using Indian scale for assessment of autism (ISAA), Oro- motor and sensory profile at baseline, after three and six months. RESULTS: Difference between change in mean ISAA score between FMI and EIBI group at the end of 6 months as per protocol (PP) analysis was -7.23 (CI=-18.41, 3.94), which was within pre-defined clinically relevant non-inferiority (NI) margin of - 24. FMI was found to be non-inferior to EIBI at the end of 6 months as the lower bound of 95% CI (-18.41) for ISAA score was higher than NI margin. ISAA scores were found to be statistically lower in both FMI and EIBI groups at the end point compared to baseline which indicated improvement in symptom severity. CONCLUSION: FMI was non-inferior to EIBI as therapy for children with ASD at the end of six months. Finding also indicated longer duration of treatment is required for FMI to be superior. FMI can be recommended for children with ASD in view of improved ISAA scores reported in our study. CLINICAL TRIAL REGISTRATION NUMBER: CTRI/2020/08/027099 (Registered with Clinical Trials Registry- India).

Radiological complexity of nuclear facilities: an information complexity approach to workplace monitoring.

Nuclear energy is crucial for achieving net-zero carbon emissions. A big challenge in the nuclear sector is ensuring the safety of radiation workers and the environment, while being cost-effective. Workplace monitoring is key to protecting workers from risks of ionising radiation. Traditional monitoring involves radiological surveillance via installed radiation monitors, continuously recording measurements like radiation fields and airborne particulate radioactivity concentrations, especially where sudden radiation changes could significantly impact workers. However, this approach struggles to detect incremental changes over a long period of time in the radiological measurements of the facility. To address this limitation, we propose abstracting a nuclear facility as a complex system. We then quantify the information complexity of the facility's radiological measurements using an entropic metric. Our findings indicate that the inferences and interpretations from our abstraction have a firm basis for interpretation and can enhance current workplace monitoring systems. We suggest the implementation of a radiological complexity-based alarm system to complement existing radiation level-based systems. The abstraction synthesized here is independent of the type of nuclear facility, and hence is a general approach to workplace monitoring at a nuclear facility.

Phyto-pharmacological Potential of Aegle marmelos (L.) for Neurological Disorders: Progress and Prospects.

BACKGROUND: Aegle marmelos, an Indian plant, has been extensively utilized by the people of the Indian subcontinent over about 5000 years. The leaves, bark, roots, and fruits, including seeds, are widely used to cure a variety of diseases in the Indian traditional system of medicine, Ayurveda, along with numerous folk medicines. By revealing the existence of significant bioactive chemicals, modern research has effectively substantiated the therapeutic effects of bael. OBJECTIVE: The objective of this study was to review the literature regarding A. marmelos geographical distribution, morphology, therapeutic benefits, and phytochemicals found in the bael leaves, fruits, and other parts of the plant that offer a wide range of pharmacological applications in neurological disorders. METHODOLOGY: A thorough literature search was conducted using five computerized databases, such as PubMed, Google Scholar, ScienceDirect, Elsevier, and Wiley Online Library (WOL), by using standard keywords "A. marmelos," "Geographical distribution," "Morphological description," "Ethnobotanical Uses," "Phytoconstituents" and "Neuroprotective activities" for review papers published between 1975 and 2023. A small number of earlier review articles focused on phyto-pharmacological potential of Aegle marmelos (L.) for neurological disorders. RESULTS: According to some research, Aegle marmelos extracts potentially have neuroprotective benefits. This is due to its capacity to alter cellular mechanisms that cause neuronal damage. CONCLUSION: Neurodegenerative illnesses usually induce permanent neuronal network loss overall the brain along with the spinal cord (CNS), resulting in chronic functional impairments. The review summarizes the multiple aspects and processes of A. marmelos extract and its components in several models of neurodegenerative diseases such as anxiety, epilepsy, depression, Parkinson's disease, Alzheimer's disease, and others. MDA, nitrite, TNF-, and IL-6 levels were dramatically elevated, whereas glutathione levels were significantly lowered in the hippocampus of STZ-treated rats. Furthermore, STZ-treated rats showed a substantial drop in catalase activity and an increase in AChE activity, indicating cholinergic hypofunction and neuronal injury. The neuroprotective ability of A. marmelos against STZ-induced oxidative stress and cognitive loss in rats suggests that it has therapeutic relevance in Alzheimer's disease (AD).

Health risk assessment of heavy metals in saffron (Crocus sativus L.) cultivated in domestic wastewater and lake water irrigated soils.

Irrigation of crops with domestic wastewater (DW) is a common practice in developing countries like India. However, domestic wastewater irrigation poses a risk of migration of toxic heavy metals to edible parts of crops, which requires serious measures to prevent their uptake. In this study, the effect of DW irrigation in comparison with Sarbal Lake water (SLW) and borewell water (BW) on soil characteristics and cultivated saffron (Crocus sativus L.) was investigated. For this purpose, samples of water, soil, and saffron (corm, petal, and stigma) were collected from the suburban area of Pampore, Srinagar district, Jammu and Kashmir, India. The results showed that DW irrigation had the maximum significant (p < 0.05) influence on the physico-chemical and nutrient characteristics of the soil, followed by SLW and BW irrigation, respectively. The growth and yield parameters of saffron were also significantly (p < 0.05) increased in the case of DW irrigation as compared to SLW and BW. The quality ranking of the cultivated saffron was found to be in accordance with the ISO standard (III: BW and II: DW and SLW). On the other hand, DW irrigation showed a significant increase in heavy metal contents (mg/kg) of saffron plant parts such as As (0.21-0.40), Cd (0.04-0.09), Cr (0.16-0.41), Cu (7.31-14. 75), Fe (142.38-303.15), Pb (0.18-0.31), Mn (15.26-22.81), Hg (0.18-0.25), Ni (0.74-1.18), Se (0.13-0.22), and Zn (3.44-4.59), followed by SLW and BW. However, the levels of heavy metals did not exceed the FAO/WHO safe limits. Bioaccumulation factor (BAF), dietary intake modeling (DIM<0.006496), health risk assessment (HRI<0.028571), and target hazard quotient (THQ<1) analyses showed no potential health hazard associated with the consumption of saffron irrigated with DW and SLW. Therefore, the results of this study provide valuable insights into the optimization of irrigation sources for saffron cultivation.