Exploring the Magnetic Interactions in Two Novel Cyanide-bridged Homo- and Heterometallic Hexadecanuclear Complexes.

Two novel isostructural cyanide-bridged hexadecanuclear complexes with the general formula {[Fe(CN)6]6[M{en(Bn)py}]10}2+ [M = Fe (12+), Ni (22+)] have been synthesized. The structural analyses disclose the presence of multivalent Fe centres with different spin states in complex 12+ whereas all the Fe centres share a conserved oxidation state in complex 22+. The DC magnetic study revealed antiferromagnetic interactions between the adjacent metal centres and ferrimagnetic behaviour in 12+. On the other hand, ferromagnetic interactions were observed in complex 22+ due to nearly orthogonal orientation of the interacting orbitals and poor spatial overlap as observed in BS-DFT calculations.

Er3+-activated Ba2V2O7 upconversion nanosheets for dual-mode temperature sensing.

So far, there has been substantial research on non-contact luminescence thermometry approaches that rely on luminescence intensity ratio (LIR) technology. However, there is limited availability of phosphors doped with Er3+ ions that exhibit on-par luminescence and high sensitivity. In this work, samples of Ba2V2O7:Er3+ were synthesized using a sol-gel method aided by citric acid. The luminescence properties of these samples, including upconversion and down-shifting, were investigated using both ultraviolet and 980 nm laser stimulation. When subjected to ultraviolet (UV) light, the sample exhibits a distinct broadband emission that appears pale green. This emission is a distinguishing property of the sample and is attributed to the presence of V2O72- ions. Upon being stimulated by a 980 nm laser, the sample exhibits standard green up-conversion Er3+ emission bands. Concurrently, an assessment was conducted on the phosphor's ability to measure temperature by analysing the LIR between the thermally coupled 2H11/2, 4S3/2 energy levels (TCELs) and the non-thermally coupled 2H11/2, 4F9/2 energy levels (NTCELs) of the Er3+ ion. The corresponding highest sensitivity of temperature for TCELs and NTCELs can position Ba2V2O7:Er3+ nanosheets as a capable option for materials utilized in temperature-sensing applications.

Recent updates on remediation approaches of environmentally occurring pollutants using visible light-active nano-photocatalysts.

Photocatalysis emerges as a potential remedy for the issue of an unreliable light source. Recognized as the most dependable and potent energy source sustaining life on Earth, sunlight offers a promising solution. Sunlight is abundant and free, operational costs associated with running photocatalytic system using nanoparticles are often lower compared to system relying on artificial light source. The escalating problem of water pollution, particularly in highly industrialized nations, necessitates effective wastewater treatment methods. These methods aim to combat elevated pollution levels, encompassing pharmaceuticals, dyes, flame retardants, and pesticide components. Advanced oxidation processes within photocatalytic wastewater treatment exhibit substantial promise for removing complex organic pollutants. Doped nanomaterials, with their enhanced properties, enable efficient utilization of light. Coupled nanomaterials present significant potential in addressing both water and energy challenges by proficiently eliminating persistent pollutants from environment. Photocatalysis when exposed to sunlight can absorb photons and generate e- h + pairs. This discussion briefly outlines the wastewater treatment facilitated by interconnected nanomaterials, emphasizing their role in water-energy nexus. In exploring the capabilities of components within a functional photocatalyst, a comprehensive analysis of both simple photocatalysts and integrated photocatalytic systems is undertaken. Review aims to provide detailed explanation of the impact of light source on photon generation and significance of solar light on reaction kinetics, considering various parameters such as catalyst dosage, pH, temperature, and types of oxidants. By shedding light on these aspects, this review seeks to enhance our understanding of intricate processes involved in photocatalysis and its potential applications in addressing contemporary environmental challenges.

Empagliflozin-A Sodium Glucose Co-transporter-2 Inhibitor: Overview of Its Chemistry, Pharmacology, and Toxicology.

BACKGROUND: Empagliflozin is a sodium glucose co-transporter-2 (SGLT2) inhibitor that has gained significant attention in the treatment of type 2 diabetes mellitus. Understanding its chemistry, pharmacology, and toxicology is crucial for the safe and effective use of this medication. OBJECTIVE: This review aims to provide a comprehensive overview of the chemistry, pharmacology, and toxicology of empagliflozin, synthesizing the available literature to present a concise summary of its properties and implications for clinical practice. METHODS: A systematic search of relevant databases was conducted to identify studies and articles related to the chemistry, pharmacology, and toxicology of empagliflozin. Data from preclinical and clinical studies, as well as post-marketing surveillance reports, were reviewed to provide a comprehensive understanding of the topic. RESULTS: Empagliflozin is a selective SGLT2 inhibitor that works by constraining glucose reabsorption in the kidneys, causing increased urinary glucose elimination. Its unique mechanism of action provides glycemic control, weight reduction, and blood pressure reduction. The drug's chemistry is characterized by its chemical structure, solubility, and stability. Pharmacologically, empagliflozin exhibits favorable pharmacokinetic properties with rapid absorption, extensive protein binding, and renal elimination. Clinical studies have demonstrated its efficacy in improving glycemic control, reducing cardiovascular risks, and preserving renal function. However, adverse effects, for instance, urinary tract infections, genital infections, and diabetic ketoacidosis have been reported. Toxicological studies indicate low potential for organ toxicity, mutagenicity, or carcinogenicity. CONCLUSION: Empagliflozin is a promising SGLT2 inhibitor that offers an innovative approach to the treatment of type 2 diabetes mellitus. Its unique action mechanism and favorable pharmacokinetic profile contribute to its efficacy in improving glycemic control and reducing cardiovascular risks. While the drug's safety profile is generally favorable, clinicians should be aware of potential adverse effects and monitor patients closely. More study is required to determine the longterm safety and explore potential benefits in other patient populations. Overall, empagliflozin represents a valuable addition to the armamentarium of antidiabetic medications, offering significant benefits to patients suffering from type 2 diabetes mellitus. This study covers all aspects of empagliflozin, including its history, chemistry, pharmacology, and various clinical studies, case reports, and case series.

Is Atopic Dermatitis a Risk Factor for Thyroid Autoimmunity? - A Cross-Sectional Study from a Tertiary Care Center in India.

Background: Because of the counter-regulation of Th1 and Th2 cells, Th1-type autoimmune diseases like thyroid autoimmunity and Th2-mediated allergic diseases like atopic dermatitis (AD) should occur in mutually exclusive populations. However, thyroid autoimmunity has been associated with chronic urticaria, and atopy is considered a cause of both AD and urticaria. Objectives: To assess the frequency of thyroid autoimmunity in children with AD and to study the correlation between the clinical severity of AD using the SCORing Atopic Dermatitis (SCORAD) score, and biochemical parameters of serum immunoglobulin E (IgE), absolute eosinophil count, and vitamin D levels. Materials and Methods: A hospital-based cross-sectional study was conducted, recruiting children (0-18 years) with AD. Patients on drugs affecting thyroid dysfunction and those with sick euthyroid syndrome or an immunodeficiency disorder were excluded. Clinical severity was assessed using SCORAD, and the thyroid profile, anti-thyroid peroxidase antibodies, antinuclear antibody (ANA), absolute eosinophil count, serum IgE, and vitamin D levels were measured. Results: Thyroid autoimmunity was diagnosed in 18.9% (10/53) of children. There was a significant correlation between SCORAD and serum IgE (r = 0.432, P = 0.002) and absolute eosinophil count (r = 0.575, P = <0.001). There was a negative correlation between SCORAD and vitamin D levels (r = -0.373, P = 0.006). Conclusions: Thyroid autoimmunity may be associated with AD, and a high index of suspicion is essential. Vitamin D also should be supplemented in children with AD as it is frequently found to be low, especially in severe cases. Multi-center case-control studies are required to determine the prevalence of thyroid autoimmunity in children with AD.

Developmental stage-specific proteome analysis of the legume pod borer Maruca vitrata provides insights on relevant proteins.

The spotted pod borer, Maruca vitrata (Lepidoptera: Crambidae) is a destructive insect pest that inflicts significant productivity losses on important leguminous crops. Unravelling insect proteomes is vital to comprehend their fundamental molecular mechanisms. This research delved into the proteome profiles of four distinct stages -three larval and pupa of M. vitrata, utilizing LC-MS/MS label-free quantification-based methods. Employing comprehensive proteome analysis with fractionated datasets, we mapped 75 % of 3459 Drosophila protein orthologues out of which 2695 were identified across all developmental stages while, 137 and 94 were exclusive to larval and pupal stages respectively. Cluster analysis of 2248 protein orthologues derived from MaxQuant quantitative dataset depicted six clusters based on expression pattern similarity across stages. Consequently, gene ontology and protein-protein interaction network analyses using STRING database identified cluster 1 (58 proteins) and cluster 6 (25 proteins) associated with insect immune system and lipid metabolism. Furthermore, qRT-PCR-based expression analyses of ten selected proteins-coding genes authenticated the proteome data. Subsequently, functional validation of these chosen genes through gene silencing reduced their transcript abundance accompanied by a marked increase in mortality among dsRNA-injected larvae. Overall, this is a pioneering study to effectively develop a proteome atlas of M. vitrata as a potential resource for crop protection programs.

Genome-wide transcriptomic and biochemical profiling of major depressive disorder: Unravelling association with susceptibility, severity, and antidepressant response.

Identifying biomarkers for diagnosing Major Depressive Disorder (MDD), assessing its severity, and guiding treatment is crucial. We conducted whole genome transcriptomic study in North Indian population, and analyzed biochemical parameters. Our longitudinal study investigated gene-expression profiles from 72 drug-free MDD patients and 50 healthy controls(HCs) at baseline and 24 patients after 12-weeks of treatment. Gene expression analyses identified differentially expressed genes(DEGs) associated with MDD susceptibility, symptom severity and treatment response, independently validated by qPCR. Hierarchical clustering revealed distinct expression patterns between MDD and HCs, also between mild and severe cases. Enrichment analyses of significant DEGs revealed inflammatory, apoptosis, and immune-related pathways in MDD susceptibility, severity, and treatment response. Simultaneously, we assessed thirty biochemical parameters in the same cohort, showed significant differences between MDD and HCs in 13 parameters with monocytes, eosinophils, creatinine, SGPT, and total protein remained independent predictors of MDD in a multivariate-regression model. Our study supports the role of altered immune/inflammatory signaling in MDD pathophysiology, offering clinically relevant biochemical parameters and insights into transcriptomic gene regulation in MDD pathogenesis and treatment response.

Modulation of single-chain magnet behaviour in a heterometallic Fe2Co cyanide-bridged 2D sheet.

A cyanide-bridged Fe2Co 2D sheet exhibiting electron transfer coupled spin transition (ETCST) with co-existence of magnetic ordering below 50 K is reported. The complex exhibits single-chain magnet behaviour where the uncoordinated water molecules act as an exchange-breaking impurity by allowing only a fraction of the molecule to undergo a spin state change. The paramagnetic centres prevail throughout the chain on desolvation, thereby increasing the number of correlated units in the chain.

Tailored mesoporous γ-WO3 nanoplates: unraveling their potential for highly sensitive NH3 detection and efficient photocatalysis.

Herein, the monoclinic phase of tungsten oxide (γ-WO3) was successfully obtained after annealing hydrothermally synthesised WO3 powder at 500 °C. As per the result obtained from the N2 adsorption-desorption isotherm, the material has been identified as mesoporous with a specific surface area of 3.71 m2 g-1 from BET (Brunauer-Emmett-Teller) analysis. Moreover, the average pore size (49.52 nm) and volume (0.050 cm3 g-1) were also determined by the BJH (Barrett-Joyner-Halenda) method. FE-SEM (field emission scanning electron microscopy) and HR-TEM (high resolution transmission electron microscopy) have confirmed the formation of nanoplates with an average diameter of approximately 274 nm. Raman spectroscopy has shown peaks at the lower wavenumber region (270 cm-1 and 326 cm-1) and the higher wavenumber region (713 cm-1 and 806 cm-1) for O-W-O bending modes and stretching modes, respectively. The combined effect of relative humidity (RH-11%-RH-95%-RH-11%) and NH3 (150 ppm, 300 ppm, 450 ppm, 600 ppm, 700 ppm, and 800 ppm) was investigated in this reported work. The synthesised γ-WO3 has shown highly responsive behaviour for humidity of 96.5% (RH-11%-95%) and NH3 sensing (under humidity) of 97.4% (RH-11%-95% with 800 ppm NH3). The response and recovery time were calculated as 15 s and 52 s, and 16 s and 54 s for humidity, and NH3 under humidity, respectively. The experimental findings demonstrated that the resistance of the sensor depends on the concentration of NH3 and humidity. Moreover, γ-WO3 has been investigated as a promising catalyst for the dye degradation of methylene blue (MB) with a degradation efficiency of 72.82% and methyl orange (MO) with a degradation efficiency of 53.84% under visible light exposure. This dye degradation occurred within 160 min in the presence of a catalyst under visible light irradiation.

Implementation research: Road map from research to practice.

The challenge today is to make sure that the evidence available gets implemented for betterment of human wellbeing. The research which is closely associated with implementation, challenges and outcome of evidence in real life scenario is Implementation research (IR). The current prespective explains why there is a focus on IR by all icluding researchers, practitioners and policy makers. The approaches and study designs commonly used in the IR have been described. The IR is multi-disciplinary, multilevel and contextual in nature. The outcomes in IR are proximal. The article further describes the ethical issue and the way forward for IR. We need to do capacity building of practitioners, researchers and policymakers in IR.

Granulomatous Vulvitis: A Rare Case of Chronic Inflammatory Hypertrophy of Vulvar Labia Related to Ulcerative Colitis.

Granulomatous vulvitis (GV) is an idiopathic entity typically presenting with chronic, painless swelling of the genitals with histologic evidence of granulomatous inflammation. Granulomatous vulvitis can typically start as an acute inflammatory condition, which gradually transforms into a chronic disease with a relapsing and remitting course leading to swollen, indurated, and distorted external genitalia. Association of GV with Crohn's disease is being increasingly recognized. However, the association of GV with ulcerative colitis is unreported. Here, we report a rare case of GV in a middle-aged Indian female with characteristic gastrointestinal involvement suggestive of ulcerative colitis. We hope to contribute to an earlier recognition and a better management of the vulvar and gastrointestinal lesions of ulcerative colitis.

Metronomic Administration of Topotecan Alone and in Combination with Docetaxel Inhibits Epithelial-mesenchymal Transition in Aggressive Variant Prostate Cancers.

Prostate cancer is the second leading cause of noncutaneous cancer-related deaths in American men. Androgen deprivation therapy (ADT), radical prostatectomy, and radiotherapy remain the primary treatment for patients with early-stage prostate cancer (castration-sensitive prostate cancer). Following ADT, many patients ultimately develop metastatic castration-resistant prostate cancer (mCRPC). Standard chemotherapy options for CRPC are docetaxel (DTX) and cabazitaxel, which increase median survival, although the development of resistance is common. Cancer stem-like cells possess mesenchymal phenotypes [epithelial-to-mesenchymal transition (EMT)] and play crucial roles in tumor initiation and progression of mCRPC. We have shown that low-dose continuous administration of topotecan (METRO-TOPO) inhibits prostate cancer growth by interfering with key cancer pathway genes. This study utilized bulk and single-cell or whole-transcriptome analysis [(RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq)], and we observed greater expression of several EMT markers, including Vimentin, hyaluronan synthase-3, S100 calcium binding protein A6, TGFB1, CD44, CD55, and CD109 in European American and African American aggressive variant prostate cancer (AVPC) subtypes-mCRPC, neuroendocrine variant (NEPC), and taxane-resistant. The taxane-resistant gene FSCN1 was also expressed highly in single-cell subclonal populations in mCRPC. Furthermore, metronomic-topotecan single agent and combinations with DTX downregulated these EMT markers as well as CD44+ and CD44+/CD133+ "stem-like" cell populations. A microfluidic chip-based cell invasion assay revealed that METRO-TOPO treatment as a single agent or in combination with DTX was potentially effective against invasive prostate cancer spread. Our RNA-seq and scRNA-seq analysis were supported by in silico and in vitro studies, suggesting METRO-TOPO combined with DTX may inhibit oncogenic progression by reducing cancer stemness in AVPC through the inhibition of EMT markers and multiple oncogenic factors/pathways. Significance: The utilization of metronomic-like dosing regimens of topotecan alone and in combination with DTX resulted in the suppression of makers associated with EMT and stem-like cell populations in AVPC models. The identification of molecular signatures and their potential to serve as novel biomarkers for monitoring treatment efficacy and disease progression response to treatment efficacy and disease progression were achieved using bulk RNA-seq and single-cell-omics methodologies.

Efficient photo-adsorptive eradication of endocrine disrupting pesticides by chitosan co- decorated metal oxide bio-nanocomposite.

Extensive consumption, toxicity and bioaccumulation of malathion (MLT) and lindane (γ-HCH) pesticides collectively attract the world's attention. Herein, the nanocomposite of chitosan wrapped NiO@ZnO was synthesized by a green methodology using Azadirachta indica leaves extract. Structural and morphological analysis of chitosan-NiO@ZnO showed hollow sphere-flake shaped image adsorbed on a solid chitosan surface with a large surface area of 73 m2g-1. A decrease in values of lattice strain, dislocation density and crystallite size described the imperfection in crystal geometry and new peaks in FT-IR spectra at 698 cm-1 and 448 cm-1 of Ni-N and Zn-N, which respectively confirm the coupling. Chitosan-NiO@ZnO and individual nanoparticles (NiO and ZnO) were well-characterized and utilized for degradation MLT and γ-HCH under direct sunlight and dark conditions. The highest degradation of pesticides (above 94%) resulted with 2 mg L-1 and 10 mg L-1 of MLT (π-π) and γ-HCH, respectively with a 20 mg catalyst dose, and pH of ~ 7 under daylight exposure (5 h). Chitosan-NiO@ZnO substantially suppressed the half-life of the targeted pesticides (MLT: 0.48 h; HCH 0.51 h) and demonstrated the first-order kinetics with a high adsorption capacity, Xm (MLT: 14.5 mg g-1 and γ-HCH 20.7 mg g-1), which also confirmed the strong binding with the pesticides, followed by their conversion into safer and smaller metabolites. The charge separation mechanism was elucidated by UV reflectance and photoluminescence data. Hydroxyl radicals were most frequently responsible for the degradation of pesticides as confirmed by scavenger analysis. The synthesized green-nano photocatalyst showed high reusability (up to 10th cycles), sensitivity and stability within the degradation process, presumably making it suitable for industrial applications.

Piperazine-1,2,3-triazole scaffolds: design, synthesis, anticancer and antimicrobial evaluation.

Aim: The objective of the present study is to design and synthesize diverse piperazine-1,2,3-triazole scaffolds as key pharmacophores possessing antimicrobial/anticancer activities. Materials & methods: Twenty-four scaffolds were synthesized via a click-inspired synthetic protocol and were assayed for anticancer activity using the methyl thiazolyl tetrazolium assay and for antimicrobial potency by serial dilution. Results: Among all the tested 1,2,3-triazole scaffolds, compounds 7i (IC50: 5.22 ± 0.05 µM) and 7a (IC50: 5.34 ± 0.13 µM) exhibited good anticancer activity, and 7x also showed notable antimicrobial activity. Molecular docking studies of potent analogs 7i and 7a were performed to provide an insight into their binding interactions. Conclusion: Compound 7x is considered a valuable lead compound for further optimization of anticancer and antimicrobial agents.

Synthesis of plant-based, self-adjuvanted, dual antigen specific to Mycobacterium tuberculosis as a novel tuberculosis subunit vaccine that elicits immunogenicity in rabbit.

OBJECTIVES: The only approved vaccine, Bacillus Calmette Guérin (BCG) used in global tuberculosis (TB) immunization programmes has been very effective in childhood TB but not in adult pulmonary and latent TB. Moreover, the emergence of multi-drug resistance-TB cases demands either to increase efficiency of BCG or replace it with the one with improved efficacy. RESULTS: A novel combination of two most effective secreted protein antigens specific for Mycobacterium tuberculosis (Mtb), ESAT-6 and MPT-64 (but not present in BCG strains) fused with a cholera toxin B subunit (CTB) and tagged with 6xHis was expressed for the first time in Escherichia coli as well as in transgenic cucumber plants developed using Agrobacterium tumefaciens-mediated transformation. The recombinant fusion protein (His6x.CTB-ESAT6-MPT64) expressed in E. coli was purified by a single-step affinity chromatography and used to produce polyclonal antibodies in rabbit. The transgenic cucumber lines were confirmed by polymerase chain reaction (PCR), Southern blot hybridization, reverse transcriptase PCR (RT-PCR), real-time PCR (qRT-PCR) and expression of recombinant fusion protein by western blot analysis and its quantification by enzyme-linked immunosorbent assay (ELISA). A maximum value of the fusion protein, 478 ng.g-1 (0.030% of the total soluble protein) was obtained in a transgenic cucumber line. Rabbit immunized orally showed a significant increase in serum IgG levels against the fusion protein as compared to the non-immunized rabbit. CONCLUSIONS: Stable expression of Mtb antigens with CTB in edible cucumber plants (whose fruits are eaten raw) in sufficient amount possibly would facilitate development of a safe, affordable and orally delivered self-adjuvanted, novel dual antigen based subunit vaccine against TB.

Phytoremediation of PAH compounds by microbial communities in sodic soil.

The PAH degrading microbial consortium was collected from sodic soil of the nursery of Guru Jambheshwar University of Science and Technology, Hisar, Haryana (India). And the soil was artificially amended with phenanthrene and naphthalene to isolate the PAHs degrading microbial consortium. The diversity of microbial consortium was analyzed using the NGS (Next Generation Sequencing) based metagenomic approach. The result of diversity analysis showed species Tepidanaerobacter syntrophicus, Sphingomonas oliophenolica, Arthrobacter psychrochitinipnius, Bifidobacterium bombi, Nocardiodies islandensis, Rhodovibrio sodomensis, Thiorhodococus pfennigii, Aeromicrobium ponti, Steroidobacter dentrificans, Actinomaduria maheshkhaliensis, Dactylosporangium maewongense, Pelotomaculum isophthalicicum, and Nocardioides islandensis were present in the consortium. Moreover, Sphingomonas, Arthrobacter, Sphingobium, Azospirillium, Thirohodococcus, and Pelotomaculum were the prominent pollutant degrader genera in the microbial consortium. Since the bioremediation of these pollutants occurs with a significant reduction in toxicity, the study's perspective is to use this type of consortium for bioremediation of specifically contaminated soil.

The present work's novelty was to find the helpful microbial consortium for the bioremediation of toxic compounds such as naphthalene and phenanthrene. In this study, the degradation of such compounds was done by the various communities of genera like Bifidobacterium, Conexibacter, Sterodobacter, Rhodovibrio, Arthrobacter, Actinomadura, and Euzebya, which are rarely described in the earlier researches. Therefore, this study will enhance the quality of future research.

Genetic Landscape of Major Depressive Disorder: Assessment of Potential Diagnostic and Antidepressant Response Markers.

BACKGROUND: The clinical heterogeneity in major depressive disorder (MDD), variable treatment response, and conflicting findings limit the ability of genomics toward the discovery of evidence-based diagnosis and treatment regimen. This study attempts to curate all genetic association findings to evaluate potential variants for clinical translation. METHODS: We systematically reviewed all candidates and genome-wide association studies for both MDD susceptibility and antidepressant response, independently, using MEDLINE, particularly to identify replicated findings. These variants were evaluated for functional consequences using different in silico tools and further estimated their diagnostic predictability by calculating positive predictive values. RESULTS: A total of 217 significantly associated studies comprising 1200 variants across 545 genes and 128 studies including 921 variants across 412 genes were included with MDD susceptibility and antidepressant response, respectively. Although the majority of associations were confirmed by a single study, we identified 31 and 18 replicated variants (in at least 2 studies) for MDD and antidepressant response. Functional annotation of these 31 variants predicted 20% coding variants as deleterious/damaging and 80.6% variants with regulatory effect. Similarly, the response-related 18 variants revealed 25% coding variant as damaging and 88.2% with substantial regulatory potential. Finally, we could calculate the diagnostic predictability of 19 and 5 variants whose positive predictive values ranges from 0.49 to 0.66 for MDD and 0.36 to 0.66 for response. CONCLUSIONS: The replicated variants presented in our data are promising for disease diagnosis and improved response outcomes. Although these quantitative assessment measures are solely directive of available observational evidence, robust homogenous validation studies are required to strengthen these variants for molecular diagnostic application.

Host-delivered RNAi-mediated silencing using fusion cassettes of different functional groups of genes precludes Meloidogyne incognita multiplication in Nicotiana tabacum.

KEY MESSAGE: This study demonstrates multi-gene silencing approach for simultaneous silencing of several functional genes through a fusion gene strategy for protecting plants against root-knot nematode, Meloidogyne incognita. The ability of root-knot nematode (RKN), Meloidogyne incognita, to cause extensive yield decline in a wide range of cultivated crops is well-documented. Due to the inadequacies of current management approaches, the alternatively employed contemporary RNA interference (RNAi)-based host-delivered gene silencing (HD-RNAi) strategy targeting different functional effectors/genes has shown substantial potential to combat RKNs. In this direction, we have explored the possibility of simultaneous silencing of four esophageal gland genes, six plant cell-wall modifying enzymes (PCWMEs) and a serine protease gene of M. incognita using the fusion approach. In vitro RNAi showed that combinatorial gene silencing is the most effective in affecting nematode behavior in terms of reduced attraction, penetration, development, and reproduction in tomato and adzuki beans. In addition, qRT-PCR analysis of M. incognita J2s soaked in fusion-dsRNA showed perturbed expression of all the genes comprising the fusion construct confirming successful dsRNA processing which is also supported by increased mRNA abundance of five key-RNAi pathway genes. In addition, hairpin RNA expressing constructs of multi-gene fusion cassettes were developed and used for generation of Nicotiana tabacum transgenic plants. The integration of gene constructs and expression of siRNAs in transgenic events were confirmed by Southern and Northern blot analyses. Besides, bio-efficacy analyses of transgenic events, conferred up to 87% reduction in M. incognita multiplication. Correspondingly, reduced transcript accumulation of the target genes in the M. incognita females extracted from transgenic events confirmed successful gene silencing.