MLNAS: Meta-learning based neural architecture search for automated generation of deep neural networks for plant disease detection tasks.

Plant diseases pose a significant threat to agricultural productivity worldwide. Convolutional neural networks (CNNs) have achieved state-of-the-art performances on several plant disease detection tasks. However, the manual development of CNN models using an exhaustive approach is a resource-intensive task. Neural Architecture Search (NAS) has emerged as an innovative paradigm that seeks to automate model generation procedures without human intervention. However, the application of NAS in plant disease detection has received limited attention. In this work, we propose a two-stage meta-learning-based neural architecture search system (ML NAS) to automate the generation of CNN models for unseen plant disease detection tasks. The first stage recommends the most suitable benchmark models for unseen plant disease detection tasks based on the prior evaluations of benchmark models on existing plant disease datasets. In the second stage, the proposed NAS operators are employed to optimize the recommended model for the target task. The experimental results showed that the MLNAS system's model outperformed state-of-the-art models on the fruit disease dataset, achieving an accuracy of 99.61%. Furthermore, the MLNAS-generated model outperformed the Progressive NAS model on the 8-class plant disease dataset, achieving an accuracy of 99.8%. Hence, the proposed MLNAS system facilitates faster model development with reduced computational costs.

Emergence of microgreens as a valuable food, current understanding of their market and consumer perception: A review.

Green leafy vegetables, especially microgreens are gaining popularity due to their high nutritional profiles, rich phytochemical content, and intense flavors. This review explores the growing commercial market for microgreens, especially in upscale dining and premium grocery outlets, highlighting consumer perceptions and their effect on market dynamics. Apart from these, the effect of modern agricultural methods that maximize the growth of microgreens is also examined. The value is anticipated to increase significantly, according to market predictions, from $1.7 billion in 2022 to $2.61 billion by 2029. Positive consumer views on microgreens health benefits drive this growth, although challenges such as varying levels of consumer awareness and income disparities affect sales. The review underscores the need for targeted research and strategic initiatives to enhance consumer understanding and improve cultivation methods to support market expansion in upcoming years.

Process optimization, growth kinetics, and antioxidant activity of germinated buckwheat and amaranth-based yogurt mimic.

This study aimed to investigate the integration of cereal and germinated pseudocereals into set-type yogurt mimic, resulting in a novel and nutritious product. Four groups of yogurts mimic, namely CPY-1, CPY-2, CPY-3, and CPY-4, were prepared using different probiotic cultures, including L. acidophilus 21, L. plantarum 14, and L. rhamnosus 296 along with starter cultures. Notably, CPY-2 cultured with L. plantarum and L. rhamnosus and incubated for 12 h exhibited the most desirable attributes. The resulting yogurt demonstrated an acidity of 0.65%, pH of 4.37 and a probiotic count of 6.38 log CFU/mL. The logistic growth model fit revealed maximum growth rates (k, 1/h) and maximum bacterial counts (Nm log CFU/mL) for each CPY variant. The results revealed that CPY-2 significantly improved protein, dietary fiber, phenols and antioxidant capacities compared to the control. Scanning electron microscopy showed more structured and compact casein network in CPY-2, highlighting its superior textural characteristics. Overall, this study demonstrates the incorporation of cereal and germinated pseudocereals into set-type yogurt mimic offers health benefits through increased dietary fiber and ß-glucan.

Antiproliferative effect of indeno[1,2-d]thiazolo[3,2-a]pyrimidine analogues on IL-6 mediated STAT3 and role of the apoptotic pathway in albino Wistar rats of ethyl carbamate-induced lung carcinoma: In-silico, In-vitro, and In-vivo study.

Lung cancer (LC) ranks second most prevalent cancer in females after breast cancer and second in males after prostate cancer. Based on the GLOBOCAN 2020 report, India represented 5.9% of LC cases and 8.1% of deaths caused by the disease. Several clinical studies have shown that LC occurs because of biological and morphological abnormalities and the involvement of altered level of antioxidants, cytokines, and apoptotic markers. In the present study, we explored the antiproliferative activity of indeno[1,2-d]thiazolo[3,2-a]pyrimidine analogues against LC using in-vitro, in-silico, and in-vivo models. In-vitro screening against A549 cells revealed compounds 9B (8-methoxy-5-(3,4,5-trimethoxyphenyl)-5,6-dihydroindeno[1,2-d]thiazolo[3,2-a]pyrimidine) and 12B (5-(4-chlorophenyl)-5,6-dihydroindeno[1,2-d]thiazolo[3,2-a]pyrimidine) as potential pyrimidine analogues against LC. Compounds 9B and 12B were docked with different molecular targets IL-6, Cyt-C, Caspase9, and Caspase3 using AutoDock Vina 4.1 to evaluate the binding affinity. Subsequently, in-vivo studies were conducted in albino Wistar rats through ethyl-carbamate (EC)- induced LC. 9B and 12B imparted significant effects on physiological (weight variation), and biochemical (anti-oxidant [TBAR's, SOD, ProC, and GSH), lipid (TC, TG, LDL, VLDL, and HDL)], and cytokine (IL-2, IL-6, IL-10, and IL-1ß) markers in EC-induced LC in albino Wistar rats. Morphological examination (SEM and H&E) and western blotting (IL-6, STAT3, Cyt-C, BAX, Bcl-2, Caspase3, and caspase9) showed that compounds 9B and 12B had antiproliferative effects. Accordingly, from the in-vitro, in-silico, and in-vivo experimental findings, we concluded that 9B and 12B have significant antiproliferative potential and are potential candidates for further evaluation to meet the requirements of investigation of new drug application.

Antiproliferative, apoptotic and anti-inflammatory potential of 5H-benzo[h]thiazolo[2,3-b]quinazoline analogues: Novel series of anticancer compounds.

Lung cancer (LC) is the most common cancer in males. As per GLOBOCAN 2020, 8.1 % of deaths and 5.9 % of cases of LC were reported in India. Our laboratory has previously reported the significant anticancer potential of 5H-benzo[h]thiazolo[2,3-b]quinazoline analogues. In this study, we have explored the anticancer potential of 7A {4-(6,7-dihydro-5H-benzo[h]thiazolo[2,3-b]quinazolin-7-yl)phenol} and 9A {7-(4-chlorophenyl)-9-methyl-6,7-dihydro-5H-benzo[h]thiazolo[2,3-b]quinazoline}by using in-vitro and in-vivo models of LC. In this study, we investigated the antiproliferative potential of quinazoline analogues using A549 cell line to identify the best compound of the series. The in-vitro and molecular docking studies revealed 7A and 9A compounds as potential analogues. We also performed acute toxicity study to determine the dose. After that, in-vivo studies using urethane-induced LC in male albino Wistar rats carried out further physiological, biochemical, and morphological evaluation (SEM and H&E) of the lung tissue. We have also evaluated the antioxidant level, inflammatory, and apoptotic marker expressions. 7A and 9A did not demonstrate any signs of acute toxicity. Animals treated with urethane showed a significant upregulation of oxidative stress. However, treatment with 7A and 9A restored antioxidant markers near-normal levels. SEM and H&E staining of the lung tissue demonstrated recovered architecture after treatment with 7A and 9A. Both analogues significantly restore inflammatory markers to normal level and upregulate the intrinsic apoptosis protein expression in the lung tissue. These experimental findings demonstrated the antiproliferative potential of the synthetic analogues 7A and 9A, potentially due to their anti-inflammatory and apoptotic properties.

Whole genome sequence analysis of shallot virus X from India reveals it to be a natural recombinant with positive selection pressure.

BACKGROUND: Shallots are infected by various viruses like Onion yellow dwarf virus (OYDV), Leek yellow stripe virus (LYSV), Shallot latent virus (SLV) and Shallot virus X (ShVX). In India, they have been found to be persistently infected by ShVX. ShVX also infects onion and garlic in combination with other carlaviruses and potyviruses. ShVX is a member of genus Allexivirus of family Alphaflexiviridae. ShVX has a monopartite genome, which is represented by positive sense single-stranded RNA. Globally, only six complete and 3 nearly complete genome sequences of ShV X are reported to date. This number is insufficient to measure a taxon's true molecular diversity. Moreover, the complete genome sequence of ShVX from Asia has not been reported as yet. Therefore, this study was undertaken to generate a complete genome sequence of ShVX from India. RESULTS: Shallot virus X (ShVX) is one of the significant threats to Allium crop production. In this study, we report the first complete genome sequence of the ShVX from India through Next-generation sequencing (NGS). The complete genome of the ShVX (Accession No. OK104171), from this study comprised 8911 nucleotides. In-silico analysis of the sequence revealed variability between this isolate and isolates from other countries. The dissimilarities are spread all over the genome specifically some non-coding intergenic regions. Statistical analysis of individual genes for site-specific selection indicates a positive selection in NABP region. The presence of a recombination event was detected in coat protein region. The sequence similarity percentage and phylogenetic analysis indicate ShVX Indian isolate is a distinctly different isolate. Recombination and site-specific selection may have a function in the evolution of this isolate. This is the first detailed study of the ShVX complete genome sequence from Southeast Asia. CONCLUSION: This study presents the first report of the entire genome sequence of an Indian isolate of ShVX along with an in-depth exploration of its evolutionary traits. The findings highlight the Indian variant as a naturally occurring recombinant, emphasizing the substantial role of recombination in the evolution of this viral species. This insight into the molecular diversity of strains within a specific geographical region holds immense significance for comprehending and forecasting potential epidemics. Consequently, the insights garnered from this research hold practical value for shaping ShVX management strategies and providing a foundation for forthcoming studies delving into its evolutionary trajectory.

Efficacy of Ab Interno Revision for Trabeculectomy Bleb Failure using a Minimally Invasive Approach: A Prospective Study.

PRCIS: Ab interno bleb revision using the Grover and Fellman spatula offers potential benefits in improved intraocular pressure control and spare the conjunctiva for enhanced bleb management. PURPOSE: This study aimed to evaluate the safety and effectiveness of Ab-Interno Bleb Revision (AIBR) for treating failed trabeculectomy blebs. METHODS: This non-comparative case series enrolled glaucoma patients with failed trabeculectomy blebs, who underwent AIBR and were followed up for one year. Eligible patients received subconjunctival Mitomycin C 0.1 mL of 0.2 mg/mL (20 µg) five days before the AIBR, performed using the Grover and Fellman spatula. The primary outcome measures were intraocular pressure (IOP) and the usage of IOP-lowering medications one year after the procedure. Secondary outcomes included the procedure's failure rate and complications. Complete success was defined as achieving an IOP between 5-21 mmHg without medication, while qualified success required additional medical treatment. RESULTS: The study comprised 23 eyes from 23 patients, having a mean age of 59.66±14.93 years. Preoperatively, the mean IOP was 23.54±10.7 mmHg, and the mean anti-glaucoma medication requirement was 3.99±0.65, both significantly reduced to 15.7±6.9 mm Hg (P=0.009) and 1.26±1.2 (P <0.001) at one year, respectively. Overall, 19 eyes (82.6%) achieved success (Complete success: 39.2%, Qualified success: 43.4%), while in 4 (17.4%) patients the procedure failed (IOP >21 mmHg). 5 patients had transient hyphema, but there were no sight-threatening complications such as hypotony or choroidal detachment. CONCLUSION: Ab-Interno Bleb Revision (AIBR) is a safe, effective, and minimally invasive intervention for managing failed trabeculectomy blebs. By eliminating the need to reopen the conjunctiva, this technique offers a promising alternative for the treatment of this challenging condition.

Liquisolid Technique: A Novel Technique with Remarkable Applications in Pharmaceutics.

Recently, it has been observed that newly developed drugs are lipophilic and have low aqueous solubility issues, which results in a lower dissolution rate and bioavailability of the drugs. To overcome these issues, the liquisolid technique, an innovative and advanced approach, comes into play. This technique involves the conversion of the drug into liquid form by dissolving it in non-volatile solvent and then converting the liquid medication into dry, free-flowing, and compressible form by the addition of carrier and coating material. It offers advantages like low cost of production, easy method of preparation, and compactable with thermo labile and hygroscopic drugs. It has been widely applied for BCS II drugs to enhance dissolution profile. Improving bioavailability, providing sustained release, minimizing pH influence on drug dissolution, and improving drug photostability are some of the other promising applications of this technology. This review article presents an overview of the liquisolid technique and its applications in formulation development.

Improvement in Electrochemical Performance of Waste Sugarcane Bagasse-Derived Carbon via Hybridization with SiO2 Nanospheres.

Sugar industries generate substantial quantities of waste biomass after the extraction of sugar water from sugarcane stems, while biomass-derived porous carbon has currently received huge research attention for its sustainable application in energy storage systems. Hence, we have investigated waste sugarcane bagasse (WSB) as a cheap and potential source of porous carbon for supercapacitors. The electrochemical capacitive performance of WSB-derived carbon was further enhanced through hybridization with silicon dioxide (SiO2) as a cost-effective pseudocapacitance material. Porous WSB-C/SiO2 nanocomposites were prepared via the in situ pyrolysis of tetraethyl orthosilicate (TEOS)-modified WSB biomass. The morphological analysis confirms the pyrolytic growth of SiO2 nanospheres on WSB-C. The electrochemical performance of WSB-C/SiO2 nanocomposites was optimized by varying the SiO2 content, using two different electrolytes. The capacitance of activated WSB-C was remarkably enhanced upon hybridization with SiO2, while the nanocomposite electrode demonstrated superior specific capacitance in 6 M KOH electrolyte compared to neutral Na2SO4 electrolyte. A maximum specific capacitance of 362.3 F/g at 0.25 A/g was achieved for the WSB-C/SiO2 105 nanocomposite. The capacitance retention was slightly lower in nanocomposite electrodes (91.7-86.9%) than in pure WSB-C (97.4%) but still satisfactory. A symmetric WSB-C/SiO2 105//WSB-C/SiO2 105 supercapacitor was fabricated and achieved an energy density of 50.3 Wh kg-1 at a power density of 250 W kg-1, which is substantially higher than the WSB-C//WSB-C supercapacitor (22.1 Wh kg-1).

Regulation of Notch signaling by non-muscle myosin II Zipper in Drosophila.

The Notch pathway is an evolutionarily conserved signaling system that is intricately regulated at multiple levels and it influences different aspects of development. In an effort to identify novel components involved in Notch signaling and its regulation, we carried out protein interaction screens which identified non-muscle myosin II Zipper (Zip) as an interacting partner of Notch. Physical interaction between Notch and Zip was further validated by co-immunoprecipitation studies. Immunocytochemical analyses revealed that Notch and Zip co-localize within same cytoplasmic compartment. Different alleles of zip also showed strong genetic interactions with Notch pathway components. Downregulation of Zip resulted in wing phenotypes that were reminiscent of Notch loss-of-function phenotypes and a perturbed expression of Notch downstream targets, Cut and Deadpan. Further, synergistic interaction between Notch and Zip resulted in highly ectopic expression of these Notch targets. Activated Notch-induced tumorous phenotype of larval tissues was enhanced by over-expression of Zip. Notch-Zip synergy resulted in the activation of JNK pathway that consequently lead to MMP activation and proliferation. Taken together, our results suggest that Zip may play an important role in regulation of Notch signaling.

Clinico-Etiopathogenesis of Vitamin B12, Folic Acid and Iron Deficiency in Severe Acute Malnutrition Children: A Tertiary Care Hospital Experience from Central India.

In severe acute malnutrition, micronutrient deficiency as well as protein energy malnutrition is a major obstacle to growth & development. Iron deficiency dominates the spectrum of nutritional anemia. After taking informed consent, 211 SAM children and 211 age-and sex-matched healthy children with normal nutritional status were enrolled for the study. MUAC was used to diagnose SAM. A 5-part automated hematoanalyzer was used to measure the complete blood count and red cell indices, and the peripheral smear method to determine the red cell morphology. We measured serum ferritin, Vitamin B12, and folic acid using the ELISA method. Compared to controls, children with SAM had significantly lower red cell indices, platelet counts, and white cell counts. The most common clinical symptoms seen in SAM children were diarrhea, pneumonia, acute gastroenteritis, and acute respiratory infection. Children with SAM are more likely to suffer from iron deficiency and B12 deficiency. Severe vitamin B12 deficiency was more frequently associated with severe anemia. The severe anemia in SAM children constantly changes the body's defense mechanism, affecting the haematopoiesis. In this study, haematological indices are recommended for predicting severity of anemia, and hematopoietic changes are described, in order to improve anticipatory care and outcome in children with SAM.

A Rare Entanglement: Self-Knotting of a Nasogastric Tube.

While nasogastric intubation is a commonplace procedure characterized by its utility in enteral feeding and gastrointestinal decompression, instances of unexpected complications are relatively infrequent. Herein, we describe an unusual and rare complication, knot formation, that surfaced during routine patient care. This unique case prompts a re-evaluation of the potential complications associated with nasogastric tube insertion and offers insights into the challenges faced in its management. Through this report, we aim to contribute to the understanding of rare complications in enteral feeding practices.

Dandelion (Taraxacum officinale): A Promising Source of Nutritional and Therapeutic Compounds.

BACKGROUND: Taraxacum officinale, commonly referred to as dandelion, is a selfgrowing plant/ weed in various parts of India and the rest of the world (particularly the northern hemisphere). The plant's chemical composition, including sesquiterpene lactones, saponins, flavonoids, phenols, and many other compounds, contributes positively to the human body, promoting overall health. AIM: This review aims to shed light on the therapeutic potential of dandelion by summarizing its nutritional benefits, phytochemical constituents, and effectiveness in addressing health conditions like diabetes, inflammation, and cancer. It also provides insights into the applications of this plant beyond the food industry to gain researchers' attention to unravel the unexplored aspects of this therapeutic plant. It will further help in laying specific considerations, which are required to be taken into account before the development of functional foods incorporated with dandelion. Scope and approach: Being rich in essential vitamins, minerals, and other phytoconstituents, dandelion is a natural remedy for various ailments. Whether consumed raw or cooked, the plant's inclusion in the diet poses potential therapeutic effects on conditions such as diabetes, inflammation, liver disease, and tumors. It also aids in immune system modulation and fights infections by targeting microbes at their root. Researchers have developed various value-added food products by incorporating different parts of dandelion. CONCLUSION: This review highlights the therapeutic potential of dandelion, emphasizing its effectiveness against various health conditions. Insights into dosage, toxicity, and diverse applications further underscore its role as a versatile and promising natural remedy.

Nanoinformatics based insights into the interaction of blood plasma proteins with carbon based nanomaterials: Implications for biomedical applications.

In the past three decades, interest in using carbon-based nanomaterials (CBNs) in biomedical application has witnessed remarkable growth. Despite the rapid advancement, the translation of laboratory experimentation to clinical applications of nanomaterials is one of the major challenges. This might be attributed to poor understanding of bio-nano interface. Arguably, the most significant barrier is the complexity that arises by interplay of several factors like properties of nanomaterial (shape, size, surface chemistry), its interaction with suspending media (surface hydration and dehydration, surface reconstruction and release of free surface energy) and the interaction with biomolecules (conformational change in biomolecules, interaction with membrane and receptor). Tailoring a nanomaterial that minimally interacts with protein and lipids in the medium while effectively acts on target site in biological milieu has been very difficult. Computational methods and artificial intelligence techniques have displayed potential in effectively addressing this problem. Through predictive modelling and deep learning, computer-based methods have demonstrated the capability to create accurate models of interactions between nanoparticles and cell membranes, as well as the uptake of nanomaterials by cells. Computer-based simulations techniques enable these computational models to forecast how making particular alterations to a material's physical and chemical properties could enhance functional aspects, such as the retention of drugs, the process of cellular uptake and biocompatibility. We review the most recent progress regarding the bio-nano interface studies between the plasma proteins and CBNs with a special focus on computational simulations based on molecular dynamics and density functional theory.

Comprehensive antifungal investigation of green synthesized silver nanoformulation against four agriculturally significant fungi and its cytotoxic applications.

The present study reports the green synthesis of silver nanoparticles (AgNPs) in powder form using the leaf extract of Azadirachta indica. The synthesis of AgNPs was confirmed by UV-vis spectroscopy, FTIR, XRD, FESEM, and EDX. The synthesized AgNPs were in a powdered state and dispersed completely in 5% polyethylene glycol (PEG) and demonstrated prolonged shelf life and enhanced bioavailability over a year without any aggregation. The resulting silver nanoformulation demonstrated complete inhibition against Sclerotinia sclerotiorum and Colletotrichum falcatum and 68% to 80% inhibition against Colletotrichum gloeosporioides and Rhizoctonia solani respectively, at 2000 ppm. The EC50 values determined through a statistical analysis were 66.42, 157.7, 19.06, and 33.30 ppm for S. sclerotiorum, C. falcatum, C. gloeosporioides, and R. solani respectively. The silver nanoformulation also established significant cytotoxicity, with a 74.96% inhibition rate against the human glioblastoma cell line U87MG at 250 ppm. The IC50 value for the cancerous cell lines was determined to be 56.87 ppm through statistical analysis. The proposed silver nanoformulation may be used as a next-generation fungicide in crop improvement and may also find application in anticancer investigations. To the best of our knowledge, this is also the first report of silver nanoformulation demonstrating complete inhibition against the economically significant phytopathogen C. falcatum.

Classification of Lung Diseases Using an Attention-Based Modified DenseNet Model.

Lung diseases represent a significant global health threat, impacting both well-being and mortality rates. Diagnostic procedures such as Computed Tomography (CT) scans and X-ray imaging play a pivotal role in identifying these conditions. X-rays, due to their easy accessibility and affordability, serve as a convenient and cost-effective option for diagnosing lung diseases. Our proposed method utilized the Contrast-Limited Adaptive Histogram Equalization (CLAHE) enhancement technique on X-ray images to highlight the key feature maps related to lung diseases using DenseNet201. We have augmented the existing Densenet201 model with a hybrid pooling and channel attention mechanism. The experimental results demonstrate the superiority of our model over well-known pre-trained models, such as VGG16, VGG19, InceptionV3, Xception, ResNet50, ResNet152, ResNet50V2, ResNet152V2, MobileNetV2, DenseNet121, DenseNet169, and DenseNet201. Our model achieves impressive accuracy, precision, recall, and F1-scores of 95.34%, 97%, 96%, and 96%, respectively. We also provide visual insights into our model's decision-making process using Gradient-weighted Class Activation Mapping (Grad-CAM) to identify normal, pneumothorax, and atelectasis cases. The experimental results of our model in terms of heatmap may help radiologists improve their diagnostic abilities and labelling processes.

Prebiotically plausible chemoselective pantetheine synthesis in water.

Coenzyme A (CoA) is essential to all life on Earth, and its functional subunit, pantetheine, is important in many origin-of-life scenarios, but how pantetheine emerged on the early Earth remains a mystery. Earlier attempts to selectively synthesize pantetheine failed, leading to suggestions that "simpler" thiols must have preceded pantetheine at the origin of life. In this work, we report high-yielding and selective prebiotic syntheses of pantetheine in water. Chemoselective multicomponent aldol, iminolactone, and aminonitrile reactions delivered spontaneous differentiation of pantoic acid and proteinogenic amino acid syntheses, as well as the dihydroxyl, gem-dimethyl, and ß-alanine-amide moieties of pantetheine in dilute water. Our results are consistent with a role for canonical pantetheine at the outset of life on Earth.

Enhanced translocation of TRIM32 to mitochondria sensitizes dopaminergic neuronal cells to apoptosis during stress conditions in Parkinson's disease.

Parkinson's disease (PD) is a chronic neurodegenerative disease characterized by progressive loss of dopamine-producing neurons from the substantia nigra region of the brain. Mitochondrial dysfunction is one of the major causes of oxidative stress and neuronal cell death in PD. E3 ubiquitin ligases such as Parkin (PRKN) modulate mitochondrial quality control in PD; however, the role of other E3 ligases associated with mitochondria in the regulation of neuronal cell death in PD has not been explored. The current study investigated the role of TRIM32, RING E3 ligase, in sensitization to oxidative stress-induced neuronal apoptosis. The expression of TRIM32 sensitizes SH-SY5Y dopaminergic cells to rotenone and 6-OHDA-induced neuronal death, whereas the knockdown increased cell viability under PD stress conditions. The turnover of TRIM32 is enhanced under PD stress conditions and is mediated by autophagy. TRIM32 translocation to mitochondria is enhanced under PD stress conditions and localizes on the outer mitochondrial membrane. TRIM32 decreases complex-I assembly and activity as well as mitochondrial reactive oxygen species (ROS) and ATP levels under PD stress. Deletion of the RING domain of TRIM32 enhanced complex I activity and rescued ROS levels and neuronal viability under PD stress conditions. TRIM32 decreases the level of XIAP, and co-expression of XIAP with TRIM32 rescued the PD stress-induced cell death and mitochondrial ROS level. In conclusion, turnover of TRIM32 increases during stress conditions and translocation to mitochondria is enhanced, regulating mitochondrial functions and neuronal apoptosis by modulating the level of XIAP in PD.

Neuronal exosomal miRNAs modulate mitochondrial functions and cell death in bystander neuronal cells under Parkinson's disease stress conditions.

Parkinson's Disease (PD) is a chronic neurodegenerative disorder characterized by progressive loss of midbrain dopaminergic neurons in the substantia nigra part of the brain. Pathology spread to numerous brain regions and cell types suggests that intercellular communication is essential to PD progression. Exosomes mediate intercellular communication between neurons, glia, and other cell types throughout PD-relevant brain regions. However, the mechanism remains unclear, and its implication in PD pathology, is not well understood. In the current study, we explored the role of exosomes in modulating the response to PD-relevant toxicants. In cellular models of PD, neuronal cell-derived exosomes are readily internalized by recipient neuronal cells as intact vesicles. Internalized exosomes in bystander neuronal cells localize to mitochondria and dysregulate mitochondrial functions, leading to cell death under PD stress conditions. NGS analysis of exosomes released by neuronal cells subjected to PD stress conditions showed that levels of specific miRNAs were altered in exosomes under PD stress conditions. Bioinformatic analysis of the miRNA targets revealed enriched pathways related to neuronal processes and morphogenesis, apoptosis and ageing. Levels of two miRNAs, hsa-miR-30a-5p and hsa-miR-181c-5p, were downregulated in exosomes under PD stress conditions. Expression of the identified miRNAs in neuronal cells led to their enrichment in exosomes, and exosome uptake in neuronal cells ameliorated mitochondrial dysfunction induced by PD stress conditions and rescued cell death. In conclusion, loss of enrichment of specific miRNAs, including miR-30a-5p and miR-181c-5p, under PD stress conditions causes mitochondrial dysfunction and neuronal death, and hence may lead to progression of PD.