High-throughput diagnostic markers for foliar fungal disease resistance and high oleic acid content in groundnut.

BACKGROUND: Foliar diseases namely late leaf spot (LLS) and leaf rust (LR) reduce yield and deteriorate fodder quality in groundnut. Also the high oleic acid content has emerged as one of the most important traits for industries and consumers due to its increased shelf life and health benefits. RESULTS: Genetic mapping combined with pooled sequencing approaches identified candidate resistance genes (LLSR1 and LLSR2 for LLS and LR1 for LR) for both foliar fungal diseases. The LLS-A02 locus housed LLSR1 gene for LLS resistance, while, LLS-A03 housed LLSR2 and LR1 genes for LLS and LR resistance, respectively. A total of 49 KASPs markers were developed from the genomic regions of important disease resistance genes, such as NBS-LRR, purple acid phosphatase, pentatricopeptide repeat-containing protein, and serine/threonine-protein phosphatase. Among the 49 KASP markers, 41 KASPs were validated successfully on a validation panel of contrasting germplasm and breeding lines. Of the 41 validated KASPs, 39 KASPs were designed for rust and LLS resistance, while two KASPs were developed using fatty acid desaturase (FAD) genes to control high oleic acid levels. These validated KASP markers have been extensively used by various groundnut breeding programs across the world which led to development of thousands of advanced breeding lines and few of them also released for commercial cultivation. CONCLUSION: In this study, high-throughput and cost-effective KASP assays were developed, validated and successfully deployed to improve the resistance against foliar fungal diseases and oleic acid in groundnut. So far deployment of allele-specific and KASP diagnostic markers facilitated development and release of two rust- and LLS-resistant varieties and five high-oleic acid groundnut varieties in India. These validated markers provide opportunities for routine deployment in groundnut breeding programs.

Carotenoid Extraction from Plant Tissues.

Carotenoids are the natural pigments available in nature and exhibit different colors such as yellow, red, and orange. These are a class of phytonutrients that have anti-cancer, anti-inflammatory, anti-oxidant, immune-modulatory, and anti-aging properties. These were used in food, pharmaceutical, nutraceutical, and cosmetic industries. They are divided into two classes: carotenes and xanthophylls. The carotenes are non-oxygenated derivatives and xanthophylls are oxygenated derivatives. The major source of carotenoids are vegetables, fruits, and tissues. Carotenoids also perform the roles of photoprotection and photosynthesis. In addition to the roles mentioned above, they are also involved and act as precursor molecules for the biosynthesis of phytohormones such as strigolactone and abscisic acid. This chapter briefly introduces carotenoids and their extraction method from plant tissue. Proposed protocol describes the extraction of carotenoid using solvents chloroform and dichloromethane. Reverse-phase HPLC can be performed with C30 columns using gradient elution. The column C30 is preferred to the C18 column because the C30 column has salient features, which include selective nature in the separation of structural isomers and hydrophobic, long-chain compounds, and shows the best compatibility with highly aqueous mobile phases. A complete pipeline for the extraction of carotenoids from plant tissue is given in the present protocol.

Sample Preparation from Plant Tissue for Gas Chromatography-Mass Spectrometry (GC-MS)we.

Metabolites are intermediate products formed during metabolism. Metabolites play different roles, including providing energy, supporting structure, transmitting signals, catalyzing reactions, enhancing defense, and interacting with other species. Plant metabolomics research aims to detect precisely all metabolites found within tissues of plants through GC-MS. This chapter primarily focuses on extracting metabolites using chemicals such as methanol, chloroform, ribitol, MSTFA, and TMCS. The metabolic analysis method is frequently used according to the specific kind of sample or matrix being investigated and the analysis objective. Chromatography (LC, GC, and CE) with mass spectrometry and NMR spectroscopy is used in modern metabolomics to analyze metabolites from plant samples. The most frequently used method for metabolites analysis is the GC-MS. It is a powerful technique that combines gas chromatography's separation capabilities with mass spectrometry, offering detailed information, including structural identification of each metabolite. This chapter contains an easy-to-follow guide to extract plant-based metabolites. The current protocol provides all the information needed for extracting metabolites from a plant, precautions, and troubleshooting.

Genome-Wide Mapping of Quantitative Trait Loci for Yield-Attributing Traits of Peanut.

Peanuts (Arachis hypogaea L.) are important high-protein and oil-containing legume crops adapted to arid to semi-arid regions. The yield and quality of peanuts are complex quantitative traits that show high environmental influence. In this study, a recombinant inbred line population (RIL) (Valencia-C × JUG-03) was developed and phenotyped for nine traits under two environments. A genetic map was constructed using 1323 SNP markers spanning a map distance of 2003.13 cM. Quantitative trait loci (QTL) analysis using this genetic map and phenotyping data identified seventeen QTLs for nine traits. Intriguingly, a total of four QTLs, two each for 100-seed weight (HSW) and shelling percentage (SP), showed major and consistent effects, explaining 10.98% to 14.65% phenotypic variation. The major QTLs for HSW and SP harbored genes associated with seed and pod development such as the seed maturation protein-encoding gene, serine-threonine phosphatase gene, TIR-NBS-LRR gene, protein kinase superfamily gene, bHLH transcription factor-encoding gene, isopentyl transferase gene, ethylene-responsive transcription factor-encoding gene and cytochrome P450 superfamily gene. Additionally, the identification of 76 major epistatic QTLs, with PVE ranging from 11.63% to 72.61%, highlighted their significant role in determining the yield- and quality-related traits. The significant G × E interaction revealed the existence of the major role of the environment in determining the phenotype of yield-attributing traits. Notably, the seed maturation protein-coding gene in the vicinity of major QTLs for HSW can be further investigated to develop a diagnostic marker for HSW in peanut breeding. This study provides understanding of the genetic factor governing peanut traits and valuable insights for future breeding efforts aimed at improving yield and quality.

Evaluating the in vitro wettability and coefficient of friction of a novel and contemporary reusable silicone hydrogel contact lens materials using an in vitro blink model.

PURPOSE: To evaluate the in vitro wettability and coefficient of friction of a novel amphiphilic polymeric surfactant (APS), poly(oxyethylene)-co-poly(oxybutylene) (PEO-PBO) releasing silicone hydrogel (SiHy) contact lens material (serafilcon A), compared to other reusable SiHy lens materials. METHODS: The release of fluorescently-labelled nitrobenzoxadiazole (NBD)-PEO-PBO was evaluated from serafilcon A over 7 days in a vial. The wettability and coefficient of friction of serafilcon A and three contemporary SiHy contact lens materials (senofilcon A; samfilcon A; comfilcon A) were evaluated using an in vitro blink model over their recommended wearing period; t = 0, 1, 7, 14 days for all lens types and t = 30 days for samfilcon A and comfilcon A (n = 4). Sessile drop contact angles were determined and in vitro non-invasive keratographic break-up time (NIKBUT) measurements were assessed on a blink model via the OCULUS Keratograph 5 M. The coefficient of friction was measured using a nano tribometer. RESULTS: The relative fluorescence of NBD-PEO-PBO decreased in serafilcon A by approximately 18 % after 7 days. The amount of NBD-PEO-PBO released on day 7 was 50 % less than the amount released on day 1 (6.5±1.0 vs 3.4±0.5 µg/lens). The reduction in PEO-PBO in the lens also coincided with an increase in contact angles for serafilcon A after 7 days (p < 0.05), although there were no changes in NIKBUT or coefficient of friction (p > 0.05). The other contact lens materials had stable contact angles and NIKBUT over their recommended wearing period (p > 0.05), with the exception of samfilcon A, which had an increase in contact angle after 14 days as compared to t = 0 (p < 0.05). Senofilcon A and samfilcon A also showed an increase in coefficient of friction at 14 and 30 days, respectively, compared to their blister pack values (p < 0.05). CONCLUSION: The results indicate that serafilcon A gradually depletes its reserve of PEO-PBO over 1 week, but this decrease did not significantly change the lens performance in vitro during this time frame.

Computational Study of Antimicrobial Peptides for Promising Therapeutic Applications Against Methicillin-resistant Staphylococcus Aureus.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a causative agent for multiple drug-resistant diseases and is a prime health concern. Currently, antibiotics like vancomycin, daptomycin, fluoroquinolones, linezolid, fifth-generation cephalosporin and others are available in the market for the treatment of MRSA infection. METHODS: With the increasing prevalence of drug-resistant cases, researchers are actively investigating alternative strategies to combat MRSA, including the exploration of peptide therapeutics. This study employed computational methods to prospect for potential Antimicrobial Peptides (AMPs). RESULTS: A total of One hundred and fifty antimicrobial peptides were explored based on physicochemical properties. The results showed that Clavanin B was the most appropriate candidate. Molecular Docking and Molecular Dynamics Simulation results showed the protein-peptide interaction of the MRSA target proteins, Penicillin Binding Protein 2a and Panton-Valentine Leukocidin Toxin, with the Antimicrobial Peptide Clavanin B. CONCLUSION: Currently, the antimicrobial peptide database highlights Clavanin B's role as an anti-HIV peptide. Moreover, this investigation proposes Clavanin B as a viable repurposed drug for treating MRSA, underscoring its potential deployment in the management of MRSA infections.

Reversible Reactions of Nitric Oxide with a Binuclear Iron(III) Nitrophorin Mimic.

Construction of functional synthetic systems that can reversibly bind and transport the most biologically important gaseous molecules, oxygen and nitric oxide (NO), remains a contemporary challenge. Myoglobin and nitrophorin perform these respective tasks employing a protein-embedded heme center where one axial iron site is occupied by a histidine residue and the other is available for small molecule ligation, structural features that are extremely difficult to mimic in protein-free environments. Indeed, the hitherto reported designs rely on sophisticated multistep syntheses for limiting access to one of the two axial coordination sites in small molecules. We have shown previously that binuclear Ga(III) and Al(III) corroles have available axial sites, and now report a redox-active binuclear Fe(III) corrole, (1-Fe)2 , in which each (corrolato)Fe(III) center is 5-coordinate, with one axial site occupied by an imidazole from the other corrole. The binuclear structure is further stabilized by attractive forces between the corrole π systems. Reaction of NO with (1-Fe)2 affords mononuclear iron nitrosyls, and of functional relevance, the reaction is reversible: nitric oxide is released upon purging the nitrosyls with inert gases, thereby restoring (1-Fe)2 in solutions or films.

Dental caries in children in Ireland: A systematic review.

BACKGROUND: Dental caries is the most common childhood disease worldwide. In the mid-1960s, mandatory Community Water Fluoridation (CWF) was introduced in the Republic of Ireland (RoI) aimed at reducing the prevalence and severity of dental caries in the population. In 2017, approximately, 71% of the Irish population was supplied with fluoridated drinking water. OBJECTIVES: To review all children's dental health surveys at National, Regional and County-levels conducted in the Republic of Ireland from 1950 to 2021 and describe trends in dental caries prevalence. The secondary objective was to compare dental caries experience in children living in areas with and without CWF. METHODS: Seven databases (Embase, Medline Ovid, PubMed, Cochrane, Web of Science, Scopus and Lenus Ireland) were systematically searched followed by lateral searches from reference lists. Studies reporting the caries experience of Irish children were eligible for inclusion. Two authors independently evaluated the quality of included studies using the Joanna Briggs Institute Critical Appraisal Checklist. RESULTS: Thirty-one studies were included. Over the last 70 years, at National, Regional and County levels, mean dmft/DMFT (decayed, missing and filled teeth) scores have decreased and the percentage of caries-free children has increased in 5, 8, 12, and 15-year-olds. The decline in dental caries indices observed throughout the country was greater in children living in areas with CWF. Between the 1960s and 2002, the mean dmft scores for 5-year-olds living in the RoI were reduced by approximately 82% and 69% for the fluoridated and non-fluoridated groups respectively. Reduction in the mean DMFT scores for the 12-year-olds were 75% and 71%, respectively, for the fluoridated and non-fluoridated groups. Between 1961 and 2014, reductions in the mean dmft/DMFT scores among 5 and 12-years-olds living in County Dublin were approximately 88% and 90% respectively. These results should be interpreted in the context of widespread use of fluoridated toothpaste in the RoI. CONCLUSIONS: Large reductions in the prevalence of dental caries in Irish children have been observed over the last seven decades. Greater dental caries reductions have been reported among children living in areas with CWF compared to those without CWF.

Enhancing climate change resilience in agricultural crops.

Climate change threatens global food and nutritional security through negative effects on crop growth and agricultural productivity. Many countries have adopted ambitious climate change mitigation and adaptation targets that will exacerbate the problem, as they require significant changes in current agri-food systems. In this review, we provide a roadmap for improved crop production that encompasses the effective transfer of current knowledge into plant breeding and crop management strategies that will underpin sustainable agriculture intensification and climate resilience. We identify the main problem areas and highlight outstanding questions and potential solutions that can be applied to mitigate the impacts of climate change on crop growth and productivity. Although translation of scientific advances into crop production lags far behind current scientific knowledge and technology, we consider that a holistic approach, combining disciplines in collaborative efforts, can drive better connections between research, policy, and the needs of society.

Novel combination approaches to locoregional and systemic therapy in the management of primary and metastatic liver tumors.

Several pathways and mutations must develop or be in place for the onset of cancer. Therefore, therapies should ideally target as many of these pathways as possible to improve outcomes. Combining several agents has proven to be more effective than the use of monotherapy in the treatment of renal cell carcinoma, hepatocellular carcinoma, and other cancers. Combination therapy can also include locoregional therapies such as ablation and embolization with systemic agents for synergistic effects. This review article discusses the current literature and clinical trials covering these multifactorial combination therapies in primary and metastatic liver tumors.

Genome-wide dissection of AT-hook motif nuclear-localized gene family and their expression profiling for drought and salt stress in rice (Oryza sativa).

AT-hook motif nuclear localized (AHL) genes are functionally very less explored, but their nature is very diverse. In the present study, we identified 20 AHL genes in rice. Phylogenetic analyses and evolutionary classification of AHL genes showed that they are conserved in plants, but the number of genes is still expanding in different crops and regulating new biological functions. Gene structure analysis showed that OsAHLs are with and without intron types of genes, suggesting that AHL genes added intron during evolution for neofunctionalization. The cis analysis of OsAHL genes suggested its motif diversity. In order to understand the function, 19 transcriptomes were identified from various tissues and different developmental stages of rice, and they were divided into eight groups by different temporal and spatial expression. Through co-expression analysis, 11 OsAHLs and 13 novel genes with intricate networks that control many biological pathways in rice were identified. The interactions of OsAHL proteins showed that they co-regulate important processes including flowering, reproductive organ development, and photosynthesis activity. The functionality of all 20 genes of OsAHL for drought and salt stress in leaf tissues of two contrasting genotypes (IR64 and NL44) of rice was studied using qRT-PCR. The result clearly showed significant upregulation of OsAHL genes under drought and salt conditions over the control. The differential expression between IR64 and NL44 showed a significant upregulation of OsAHL genes in NL44 as compared to the IR64 genotype under drought and salt stress. Overall, the result indicates that AHL genes might be involved in mediating drought and salt-signaling transduction pathways. The drought- and salt-tolerant nature of NL44 was also confirmed by expression profiling.

Visible light mediated synthesis of 1,3-diarylated imidazo[1,5-a]pyridines via oxidative amination of C-H catalyzed by graphitic carbon nitride.

Graphitic carbon nitride (g-C3N4) as a novel heterogeneous catalyst is employed for the visible light-mediated synthesis of the imidazo[1,5-a]pyridines via the oxidative amination of C-H bond at room temperature without the need for any additional solvent. Extensive characterization of the catalyst was performed using techniques such as FT-IR, PXRD, TGA, SEM and EDX analysis. The optimized conditions enabled the successful and expeditious conversion of a wide range of substrates to imidazo[1,5-a]pyridines in good yields; a notable advantage of this catalyst being recyclability, as it can be reused for up to five cycles without significant loss of activity. This feature makes it suitable for gram-scale synthesis of imidazo[1,5-a]pyridines. Additionally, this approach offers several benefits from a green chemistry perspective as affirmed by its favorable green chemistry metrics (GCM), including low process mass intensity (PMI), low E-factor, high atom economy (AE), and good reaction mass efficiency (RME) relative to existing protocols. In addition, chemical yield (CY), mass intensity (MI), mass productivity (MP) and optimum efficiency were also calculated. This environmentally friendly method offers multiple advantages and represents a significant advancement in the synthesis of imidazo[1,5-a]pyridines.

High confidence QTLs and key genes identified using Meta-QTL analysis for enhancing heat tolerance in chickpea (Cicer arietinum L.).

The rising global temperatures seriously threaten sustainable crop production, particularly the productivity and production of heat-sensitive crops like chickpeas. Multiple QTLs have been identified to enhance the heat stress tolerance in chickpeas, but their successful use in breeding programs remains limited. Towards this direction, we constructed a high-density genetic map spanning 2233.5 cM with 1069 markers. Using 138 QTLs reported earlier, we identified six Meta-QTL regions for heat tolerance whose confidence interval was reduced by 2.7-folds compared to the reported QTLs. Meta-QTLs identified on CaLG01 and CaLG06 harbor QTLs for important traits, including days to 50% flowering, days to maturity, days to flower initiation, days to pod initiation, number of filled pods, visual score, seed yield per plant, biological yield per plant, chlorophyll content, and harvest index. In addition, key genes identified in Meta-QTL regions like Pollen receptor-like kinase 3 (CaPRK3), Flowering-promoting factor 1 (CaFPF1), Flowering Locus C (CaFLC), Heat stress transcription factor A-5 (CaHsfsA5), and Pollen-specific leucine-rich repeat extensins (CaLRXs) play an important role in regulating the flowering time, pollen germination, and growth. The consensus genomic regions, and the key genes reported in this study can be used in genomics-assisted breeding for enhancing heat tolerance and developing heat-resilient chickpea cultivars.

Efficacy and safety of cosibelimab, an anti-PD-L1 antibody, in metastatic cutaneous squamous cell carcinoma.

BACKGROUND: Programmed cell death receptor-1 (PD-1)-blocking antibodies are approved to treat metastatic or locally advanced cutaneous squamous cell carcinoma (CSCC) cases ineligible for curative surgery or radiation. Notwithstanding, some patients experience inadequate responses or severe immune-related adverse events (AEs), indicating the need for improved therapies. Cosibelimab is a high-affinity programmed cell death-ligand 1 (PD-L1)-blocking antibody that activates innate and adaptive immunity by blocking PD-L1 interaction with PD-1 and B7-1 receptors. It is an unmodified immunoglobulin G1 subtype with a functional Fc domain capable of inducing antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. Here, we present results of the pivotal study of patients with metastatic CSCC from an open-label, multicenter, multiregional, multicohort, phase 1 trial of cosibelimab. METHODS: In this trial, participants with metastatic CSCC received cosibelimab 800 mg intravenously every 2 weeks. Primary endpoint was objective response rate (ORR) by independent central review using Response Evaluation Criteria in Solid Tumors, V.1.1. Secondary endpoints included duration of response (DOR) and safety. RESULTS: Objective response was observed in 37 of 78 participants (47.4% (95% CI: 36.0% to 59.1%)), with median follow-up of 15.4 months (range: 0.4 to 40.5) as of data cut-off. Median DOR was not reached (range: 1.4+ to 34.1+ months), with response ongoing in 73.0% of participants. Common treatment-emergent AEs (≥15%) were fatigue (26.9%), rash (16.7%), and anemia (15.4%). Eighteen participants (23.1%) experienced immune-related AEs (grade 3: n=2 (2.6%); no grade 4/5). No treatment-related deaths were reported. CONCLUSIONS: Cosibelimab demonstrated clinically meaningful ORR and DOR and was associated with a manageable safety profile. TRIAL REGISTRATION NUMBER: NCT03212404.

The discovery, structure, and function of 5-HTR1E serotonin receptor.

Serotonin (5-hydroxytryptamine, 5-HT) is a unique neurotransmitter which can regulate various biological processes by activating thirteen different receptors. These serotonin receptors are divided into seven different classes based on their structure and functions. Since these receptors co-express in various tissue and cell types and share the same ligand (5-HT), it has been a challenge for the researchers to define specific pathway and separate physiological role for each of these serotonin receptors. Though the evidence of operational diversity of these receptors is continuously emerging, much work remains to be done. 5-HTR1E is a member of 5-HT1 receptor family which belongs to G-protein coupled receptors (GPCRs). Even after three decades since its discovery, 5-HTR1E remains the least explored serotonin receptor. Very high similarity with another family member (5-HTR1F) and its non-existence in mice or rats makes 5-HTR1E a difficult target to study. Despite these challenges, recent findings on the role of 5-HTR1E in neuroprotection and diseases such as cancer, have excited many researchers to explore this receptor in detail. Here, we provide the first review of 5-HTR1E, since its discovery in 1989 to 2023. We highlight the structural and functional characteristics of this important serotonin receptor in detail and propose future directions in developing 5-HTR1E as a drug target. Video Abstract.

A Case That Will Take Your Breath Away: Acquired Methemoglobinemia Related to Trimethoprim-Sulfamethoxazole and Phenazopyridine Ingestion for Treatment of Urinary Tract Infection.

Trimethoprim-sulfamethoxazole (TMP-SMX) and phenazopyridine are individually associated with methemoglobinemia through a series of altered reduction-oxidation reactions. We report a case of methemoglobinemia associated with concurrent use of TMP/SMX and phenazopyridine in a 70-year-old woman with recurrent urinary tract infections. She presented to the emergency department for worsening back pain in the setting of recurrent urinary tract infections, concerning for pyelonephritis. During her workup, she became acutely hypoxic. The emergency department provider suspected the presence of abnormal hemoglobin. An arterial blood gas showing elevated levels of methemoglobinemia confirmed the suspicion. The combined use of TMP/SMX and phenazopyridine was thought to be the likely etiology of hypoxia. This case highlights the importance of medication management in the geriatric population, as well as the judicious use of antibiotics for urinary tract infections-a common chief complaint in the primary care setting.

Red emissive carbon dots: a promising next-generation material with intracellular applicability.

The accidental discovery of carbon dots (CDs) back in 2004 has led to their widespread use in the biomedical field. CDs have demonstrated their effectiveness in reporting 3D structures of biological specimens, identifying normal and cancer cells, and even detecting analytes within cells. However, the limitations of blue-green emitting CDs, such as their shallow penetration, photodamage, and auto-fluorescence, have hindered their practical applications. To overcome these limitations, red emissive CDs (RCDs) have been developed, which have deep tissue penetration, minimal photo-damage, low auto-fluorescence, and high imaging contrast. In this article, we present a thorough review on the use of RCDs in biomedical applications, including in vivo and in vitro bioimaging, photoacoustic imaging, monitoring temperature and polarity changes in living cells, tumour therapy, and drug delivery. With the rapid progress being made in the development of RCDs for intracellular applications, their clinical application is expected to become a reality in the near future.

Genetic mapping identified major main-effect and three co-localized quantitative trait loci controlling high iron and zinc content in groundnut.

Malnutrition is a major challenge globally, and groundnut is a highly nutritious self-pollinated legume crop blessed with ample genomic resources, including the routine deployment of genomic-assisted breeding. This study aimed to identify genomic regions and candidate genes for high iron (Fe) and zinc (Zn) content, utilizing a biparental mapping population (ICGV 00440 × ICGV 06040;). Genetic mapping and quantitative trait locus (QTL) analysis (474 mapped single-nucleotide polymorphism loci; 1536.33 cM) using 2 seasons of phenotypic data together with genotypic data identified 5 major main-effect QTLs for Fe content. These QTLs exhibited log-of-odds (LOD) scores ranging from 6.5 to 7.4, explaining phenotypic variation (PVE) ranging from 22% (qFe-Ah01) to 30.0% (qFe-Ah14). Likewise, four major main effect QTLs were identified for Zn content, with LOD score ranging from 4.4 to 6.8 and PVE ranging from 21.8% (qZn-Ah01) to 32.8% (qZn-Ah08). Interestingly, three co-localized major and main effect QTLs (qFe-Ah01, qZn-Ah03, and qFe-Ah11) were identified for both Fe and Zn contents. These genomic regions harbored key candidate genes, including zinc/iron permease transporter, bZIP transcription factor, and vacuolar iron transporter which likely play pivotal roles in the accumulation of Fe and Zn contents in seeds. The findings of this study hold potential for fine mapping and diagnostic marker development for high Fe and Zn contents in groundnut.

Hippocampal delivery of neurotrophic factor-α1/carboxypeptidase E gene prevents neurodegeneration, amyloidosis, memory loss in Alzheimer's Disease male mice.

Alzheimer's Disease (AD) is a prevalent neurodegenerative disease characterized by tau hyperphosphorylation, Aß1-42 aggregation and cognitive dysfunction. Therapeutic agents directed at mitigating tau aggregation and clearing Aß1-42, and delivery of growth factor genes (BDNF, FGF2), have ameliorated cognitive deficits, but these approaches did not prevent or stop AD progression. Here we report that viral-(AAV) delivery of Neurotrophic Factor-α1/Carboxypeptidase E (NF-α1/CPE) gene in hippocampus at an early age prevented later development of cognitive deficits as assessed by Morris water maze and novel object recognition assays, neurodegeneration, and tau hyperphosphorylation in male 3xTg-AD mice. Additionally, amyloid precursor protein (APP) expression was reduced to near non-AD levels, and insoluble Aß1-42 was reduced significantly. Pro-survival proteins: mitochondrial Bcl2 and Serpina3g were increased; and mitophagy inhibitor Plin4 and pro-inflammatory protein Card14 were decreased in AAV-NF-α1/CPE treated versus untreated AD mice. Thus NF-α1/CPE gene therapy targets many regulatory components to prevent cognitive deficits in 3xTg-AD mice and has implications as a new therapy to prevent AD progression by promoting cell survival, inhibiting APP overexpression and tau hyperphosphorylation.