Intermittent Fasting and Vitamin E Supplementation Attenuates Hypothyroidism-Associated Ophthalmopathy.

Visualization is a complex-integrated procedure of the eyes and brain that allows to see this colorful world. Hypothyroidism-associated ophthalmopathy (HAO), often known as dry eyes, swelling around the eyes, blurred vision, glaucoma, and cataracts, are some eye-related issues caused by hypothyroidism. Yet there is no permanent cure for hypothyroidism; taking medicine throughout life is the only solution to keep its harmful effects under control. This study used intermittent fasting (IF) and vitamin E (Vit.E) supplementation to prevent hypothyroidism-associated ophthalmopathy. This study hypothesized that intermittent fasting-like diet regimens and vitamin supplementation should reduce the propagation of HAO by its antioxidant potential. In the present study, experimental animals are divided into five groups: normal, hypothyroidism control, dual, Vit. E, and IF. Hypothyroidism is generated in the experimental groups by taking propylthiouracil (PTU) for 24 days while also taking IF and Vit. E supplements. The hypothyroid-induced experimental animals demonstrated an increase in IOP and lipid peroxidation while thyroid hormone levels depicted a massive decline which is a clear denotation of the effects of the thyroid on eyes and lifestyle. Ancient Ayurveda inspires these proposed therapies and has successfully reduced all the damage to the thyroid gland and the eye.

Divergent Electrochemical Synthesis of Indoles through pKa Regulation of Amides: Synthetic and Mechanistic Insights.

A divergent synthetic approach to access highly substituted indole scaffolds is illustrated. By virtue of a tunable electrochemical strategy, distinct control over the C-3 substitution pattern was achieved by employing two analogous 2-styrylaniline precursors. The chemoselectivity is governed by the fine-tuning of the acidity of the amide proton, relying on the appropriate selection of N-protecting groups, and assisted by the reactivity of the electrogenerated intermediates. Detailed mechanistic investigations based on cyclic voltametric experiments and computational studies revealed the crucial role of water additive, which assists the proton-coupled electron transfer event for highly acidic amide precursors, followed by an energetically favorable intramolecular C-N coupling, causing exclusive fabrication of the C-3 unsubstituted indoles. Alternatively, the implementation of an electrogenerated cationic olefin activator delivers the C-3 substituted indoles through the preferential nucleophilic nature of the N-acyl amides. This electrochemical approach of judicious selection of N-protecting groups to regulate pKa/E° provides an expansion in the domain of switchable generation of heterocyclic derivatives in a sustainable fashion, with high regio- and chemoselectivity.

Elucidating the Role of Atomically Dilute Copper Centers Impregnating a Phosphamide Polymer for the Preferential Hydrogen Evolution Reaction over CO2 Reduction.

Organic polymers have attracted considerable interest in designing a multifunctional electrocatalyst. However, the inferior electro-conductivity of such metal-free polymers is often regarded as a shortcoming. Herein, a nitrogen- and phosphorus-rich polymer with phosphamide functionality (PAP) in the repeating unit has been synthesized from diaminopyridine (DAP) and phenylphosphonic dichloride (PPDC) precursors. The presence of phosphamide oxygen and pyridine nitrogen in the repeating unit of PAP leads to the coordination of the CuII ion and the incorporation of 3.29 wt % in the polymer matrix (Cu30@PAP) when copper salt is used to impregnate the polymer. Combined with a spectroscopic, microscopic, and DFT study, the coordination and geometry of copper in the PAP matrix has been established to be a distorted square planar CuII in a N2O2 ligand environment where phosphamide oxygen and pyridine nitrogen of the PAP coordinate to the metal center. The copper incorporation in the PAP modulates its electrocatalytic activity. On the glassy carbon electrode, PAP shows inferior activity toward the hydrogen evolution reaction (HER) in 0.5 M H2SO4 while 3 wt % copper incorporation (Cu30@PAP) significantly improves the HER performance with an overpotential of 114 mV at 10 mA cm-2. The notable electrochemical activity with Cu30@PAP occurs due to the impregnation of Cu(II) in PAP, improved electro-kinetics, and better charge transfer resistance (Rct). When changing the electrolyte from H2SO4 to CO2-saturated bicarbonate solution at nearly neutral pH, PAP shows HER as the dominant pathway along with the partial reduction of CO2 to formate. Moreover, the use of Cu30@PAP as an electrolcatalyst could not alter the predominant HER path, and only 20% Faradaic efficiency for the CO2 reduced products has been achieved. Post-chronoamperometric characterization of the recovered catalyst suggests an unaltered valence state of the copper ion and the intact chemical structure of PAP. DFT studies unraveled that the copper sites of Cu30@PAP promote water adsorption while phosphamide-NH of the PAP can weakly hold the CO2 adduct via a hydrogen bonding interaction. A detailed calculation has pointed out that the tetra-coordinated copper centers present in the PAP frame are the reactive sites and that the formation of the [CuI-H] intermediate is the rate-limiting step for both HER and its competitive side reaction, i.e., CO2 reduction to formate or CO formation. The high proton concentration in the electrolyte of pH < 7 leads to HER as the predominant pathway. This combined experimental and theoretical study has highlighted the crucial role of copper sites in electrocatalysis, emphasizing the plausible reason for electrocatalytic selectivity.

Mechanistic Insights into the Appel Reaction Mediated by a Poly-Phosphamide Material as a Heterogeneous Catalyst.

Due to notable thermochemical stability, polyphosphamides are often regarded as flame retardants, while molecular phosphamides can serve as versatile Lewis base to catalyze diverse organic transformations. Being chemically analogous to phosphine oxide, phosphamide can also be considered as a mediator for the phosphine-mediated reaction. Herein, an amorphous polymeric material consisting of phosphamide (-NH-P(O)) in the repeating unit (POP) has been prepared via condensation of tris(2-aminoethyl)amine (TREN) and phenyl phosphinic dichloride (PPDC). The POP is isolated as a metal-free and pure organic material which is made of a strong covalent bond and the phosphamide unit is deployed in the organic framework. The presence of phosphamide in the repeating unit of the isolated amorphous POP material can be confirmed by 31P CPMAS NMR, FTIR, and Raman studies. The core-level N 2p and P 2p X-ray photoelectron spectra are in accordance with the presence of tertiary amine nitrogen attached to carbon and secondary amine nitrogen attached to phosphorus. Elemental analyses have depicted approximately 19.7% of phosphorus content in the material, which is being utilized to study the catalytic Appel reaction with 76% conversion of alcohol to a corresponding halide and TON of 462. Quasi in situ Raman study has identified that amino phosphine formed via in situ reduction of the phosphamide unit of the POP catalyzes the halogenation of primary and secondary alcohols with wide substrate scope and functional group tolerance. Kinetic studies have established a first-order dependence with respect to alcohol, while deuterium labeling experiments emphasize that the deprotonation of alcohol is the rate-limiting step. High thermal stability of the material, scope of easy catalyst recyclability, and a cumulative TON of 1386 have led the POP as an emerging pure organic material to be explored further for other phosphine-mediated organocatalysis.

Correction: Identification of Lasiodiplodia species inciting stem rot of dragon fruit in India through polyphasic approach.

[This corrects the article DOI: 10.1007/s13205-023-03754-1.].

Identification of Lasiodiplodia species inciting stem rot of dragon fruit in India through polyphasic approach.

Lasiodiplodia species commonly thrive as endophytes, saprobes, and plant pathogens in tropical and subtropical regions. Association of Lasiodiplodia species causing stem rot in dragon fruit in the coastal belt of Odisha, eastern India, has been illustrated here. The stem rot disease was characterized by yellowing of the stem, followed by softening of the stem tissues with fungal fructifications of the pathogen in the affected tissues. On the basis of macro- and micromorphological characteristics, the four fungal isolates recovered from diseased stems were identified initially as Lasiodiplodia species. By comparing DNA sequences within the NCBI GenBank database as well as performing a multigene phylogenetic analysis involving the internal transcribed spacer region (ITS-rDNA), ß-tubulin (ß-tub), and elongation factor-alpha (EF1-α) genes, the identity of Lasiodiplodia isolates was determined. The isolate CHES-21-DFCA was identified as Lasiodiplodia iraniensis (syn: L. iranensis) and the remaining three isolates, namely CHES-22-DFCA-1, CHES-22-DFCA-2, and CHES-22-DFCA-3, as L. theobromae. Although pathogenicity studies confirmed both L. iraniensis and L. theobromae were responsible for stem rot in dragon fruit, L. iraniensis was more virulent than L. theobromae. This study established the association of Lasiodiplodia species with stem rot in dragon fruit using a polyphasic approach. Further investigations are required, particularly related to on host-pathogen-weather interaction and spatiotemporal distribution across the major dragon fruit-growing areas of the country to formulate prospective disease management strategies. This is the first report on these two species of Lasiodiplodia inflicting stem rot in Hylocereus species in India.

COVID-19 Antibody Response in Patients with Thalassemia.

Background The coronavirus disease 2019 (COVID-19) can severely affect people with comorbidities such as those with diabetes, hypertension, chronic lung disease, cancer, and hemoglobinopathies. Studies assessing the clinical characteristics and immune response to COVID-19 infection in patients with thalassemia are limited. Objectives The primary objective of the study was to study the clinical pattern and the immunoglobulin G (IgG) antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with transfusion-dependent thalassemia (TDT) compared to patients without thalassemia. The secondary objective wasto study the relationship of COVID-19 severity with IgG antibody titers. Setting, Design, and Participants This case-control study was conducted at a tertiary care hospital between January 2021 and August 2022. A total of 30 patients with TDT (mean age: 12.7 years, SD: 4.7) and 30 patients without thalassemia (mean age: 13.9 years, SD: 7) who tested positive for COVID-19 in the preceding six weeks were recruited. Methods Serum samples from the cases and controls were collected after 6, 12, and 24 weeks of COVID-19 infection for IgG antibody estimation using chemiluminescent immunoassay. Outcome variables The primary variable was comparative analysis of antibody levels and clinical profile of COVID-19 in cases and controls. The secondaryvariable was association of the severity of COVID-19 with the antibody titers produced. Results Symptomatic individuals among cases (n=12) were significantly lesser than controls (n=22) (p=0.009). The median IgG titers of cases and controls were comparable at six weeks (p=0.40), but the titers were significantly lower for cases at 12 weeks (p=0.011) and 24 weeks (p=0.006). There was significant fall in titers from 6 to 12 and 24 weeks in both the groups. The titers were not affected by COVID-19 severity and pre-existing comorbidities. Conclusion Patients with TDT manifest with mild or asymptomatic COVID-19 and mount a comparable IgG antibody response to COVID-19 akin to controls. However, this serological response could not sustain over three to six months advocating the need for protection through vaccination.

A lung sound recognition model to diagnoses the respiratory diseases by using transfer learning.

Respiratory disease is one of the leading causes of death in the world. Through advances in Artificial Intelligence, it appears possible for the days of misdiagnosis and treatment of respiratory disease symptoms rather than their root cause to move behind us. The traditional convolutional neural network cannot extract the temporal features of lung sounds. To solve the problem, a lung sounds recognition algorithm based on VGGish- stacked BiGRU is proposed which combines the VGGish network with the stacked bidirectional gated recurrent unit neural network. A lung Sound Recognition Algorithm Based on VGGish-Stacked BiGRU is used as a feature extractor which is a pre-trained model used for transfer learning. The target model is built with the same structure as the source model which is the VGGish model and parameter transfer is done from the source model to the target model. The multi-layer BiGRU stack is used to enhance the feature value and retain the model. While fine-tuning of the parameter of VGGish is frozen which successfully improves the model. The experimental results show that the proposed algorithm improves the recognition accuracy of lung sounds and the recognition accuracy of respiratory diseases.

Immobilization of Phosphamide on the TiO2 Surface for Heterogeneous Phase Catalytic Appel Reaction.

Global consumption of triphenylphosphine (Ph3P) for phosphorus-mediated organic synthesis and production of the dead-end triphenylphosphine oxide (Ph3PO) waste is exceptionally high. Recycling Ph3PO and/or use of it as a reaction mediator gained significant attention. On the other end, phosphamides, traditionally used as a flame redundant, are stable analogues to Ph3PO. Herein, via a low temperature condensation reaction of methyl 4-(aminomethyl)benzoate (AMB) and diphenyl phosphinic chloride (DPPC), methyl 4-((N,N-diphenylphosphinamido)methyl)benzoate (1) has been synthesized and hydrolysis of the ester functional group of 1 leads to a phosphamide with a carboxylate terminal, 4-((N,N-diphenylphosphinamido)methyl)benzoic acid (2). The presence of phosphamide functionality (NH─P═O) in 2 can be confirmed by its characteristic Raman vibration at 999 cm-1 with expected P-N and P═O bonds distances from the single-crystal X-ray structure. In-situ hydrolysis of [Ti(OiPr)4] in the presence of 2 followed by hydrothermal heating results in immobilization of 2 on a ca. 5 nm TiO2 surface (2@TiO2). The covalent attachment of 2 via coordination through the carboxylate terminal to the TiO2 nanocrystal's surface has been established via multiple spectroscopic and microscopic studies. 2@TiO2 is further used as the heterogeneous mediator for the catalytic Appel reaction, halogenation of alcohol (typically mediated by phosphine), with a fair catalytic conversion and a recorded TON up to 31. The major advantage of the heterogeneous approach studied herein is the recovery of used 2@TiO2 from the reaction mixture via centrifugation only leaving the organic product in the supernatant, which is limiting in Ph3P-mediated homogeneous catalysis. Time-resolved Raman spectroscopy confirms amino phosphine as the active species formed in-situ during the catalytic Appel reaction. Post-catalytic characterization of the material recovered after catalysis from the reaction mixture confirms the chemical integrity and that can further be utilized for another two catalytic runs. The developed reaction scheme showcases the use of a phosphamide as a reactive analogue to Ph3PO for an organic reaction in a heterogeneous approach, and the same strategy can be explored further as a general scheme for other phosphorus-mediated reactions.

RT-PCR based detection of Pepper mild mottle virus from capsicum seeds and seed transmission assay.

Pepper mild mottle virus (PMMoV), a Tobamovirus from Virgaviridae family, is highly contagious and transmitted by seeds as well as soil in nature. PMMoV has become a greater threat to capsicum cultivation worldwide. To develop an indigenous, rapid, and sensitive protocol for routine detection of PMMoV from seeds, the sensitivity of DAS-ELISA and RT-PCR was compared in the present study. The infected seeds of California Wonder were included in the study. Through DAS-ELISA the virus was successfully detected from 20 mg of seeds. However, using RT-PCR, we were able to detect the virus even from one infected seed with reproducibility. In the present study, vertical seed transmission of the test virus was investigated by employing a grow-out test under greenhouse conditions as well as directly through RT-PCR omitting the grow-out test in three capsicum cultivars. Based on symptoms observations in grow out test, seed transmission was observed in the 3 capsicum cultivars viz., California Wonder (63.04%), Yolo Wonder (33.80%) and Doux des LAndes (33.30%). Through RT-PCR it was estimated to be 55.56% (California Wonder), 28.96% (Yolo Wonder), and 40.64% (Doux des Landes), respectively. Thus, indicating 100% seed-to-seedling PMMoV transmission and reliability of RT-PCR in direct PMMoV detection from seeds. Even a small percentage of infected seed has the potential to greatly increase the PMMoV inoculum in the field and result in 100% plant infection. Therefore, we suggest using the established procedure for PMMoV detection right from the seed. Supplementary Information: The online version contains supplementary material available at 10.1007/s13337-023-00807-0.

Low-dose ultra-high-pitch computed tomography coronary angiography: identifying the optimum combination of iteration strength and radiation dose reduction strategies to achieve true submillisievert scans

PURPOSE: To identify the optimum strength of advanced modeled iterative reconstruction (ADMIRE) to achieve the best subjective and objective image quality when combining three-dose reduction strategies, ultra-high-pitch computed tomography coronary angiography (FLASH CTCA; with single-dose ivabradine to lower heart rate), low tube voltage, and ADMIRE. METHODS: Sixty consecutive patients underwent FLASH CTCA at 100 kVp in this single-center prospective study. Single-dose ivabradine was administered to patients whose heart rate was above 75 bpm. Images were reconstructed using the three highest strengths of ADMIRE (A3, A4, and A5). Objective and subjective image quality (using a Likert scale) were evaluated in the three datasets. RESULTS: The signal strength remained unchanged but mean noise significantly reduced across the increasing strengths of ADMIRE [signal: 513.78 ± 101.7 Hounsfield units (HU) at A3, 515.6 ± 100.5 HU at A4, and 519.7 ± 107.9 HU at A5; noise: 23.4 ± 4.5 HU at A3, 20.2 ± 3.6 HU at A4, and 17.2 ± 3.3 HU at A5]. Signal-to-noise and contrast-to-noise ratios were the highest at A5, and A5 offered significantly higher Likert scores in image noise, vessel sharpness, and overall image quality than A3 or A4. Additionally, A5 did not interfere with image interpretation in any patient. CONCLUSION: Using all three dose reduction strategies during FLASH CTCA along with single-dose ivabradine administration ensures minimal radiation exposure in daily practice. In this study, A5 datasets had the best overall subjective and objective image quality despite their "plastic appearance". In the future, enhanced dose reduction can be obtained by further lowering tube voltages.

Polymorphisms and haplotypes of TLR-4/9 associated with bacterial infection, gingival inflammation/recession and oral cancer.

BACKGROUND: The expression and SNPs of innate immunity genes TLR-4/9 for bacterial infection, gingival inflammation/gingival recession (GIGR), and oral squamous cell carcinoma (OSCC) are largely unknown. PATIENTS AND METHOD: 235 specimens (120 OSCC cases, among which 85 cases with either Porphyromonas gingivalis, Fusobacterium nucleatum or Treponema denticola infection and GIGR) and 115 healthy controls were used to know the expression and polymorphisms (TLR-4: N1:rs10759931, N2:rs11536889, N3:rs1927911, N4:rs4986790; TLR-9: N5:rs5743836, N6:rs352140, N7:rs187084 and N8:rs352139) of TLR-4/9 by western blot, RT-PCR, and allele-specific (AS)-PCR followed by sequencing. RESULTS: Increased TLR-4/9 mRNA/protein expression, bacterial infection (BI) and GIGR were associated with OSCC incidence. One of the three BI and GIGR was observed in 70.83% of OSCC cases, whereas all the HC used were free from any of these three BI/GIGR. The N3: CT-genotype (Odds Ratio hereafter as O.R.=1.811, p = 0.0338), TT-genotype (O.R.=3.094, p = 0.0124), 'T'-allele (O.R.=1.821, p = 0.003), N4: AG-genotype (O.R.=2.015, p = 0.0222) and 'G'-allele (O.R.=1.86, p = 0.018) of TLR-4 as well as the N5: CC-genotype (O.R.=3.939, p = 0.0017), 'C'-allele (O.R.=1.839, p = 0.0042), N6: AA-genotype (O.R.=2.195, p = 0.0234), 'A'-allele (O.R.=1.569, p = 0.0163), N7: TC-genotype (O.R.=2.083, p = 0.0136), CC-genotype (O.R.=2.984, p = 0.003) and 'C'-allele (O.R.=1.885, p = 0.0008) of TLR-9 were associated with increased OSCC risk. Similarly, the N2:'C'-allele (O.R.=1.615, p = 0.0382), N3: TT-genotype (O.R.=2.829, p = 0.0336), 'T'-allele (O.R.=1.742, p = 0.0115), N4: AG-genotype (O.R.=2.221, p = 0.0147) and 'G'-allele (O.R.=1.890, p = 0.0238) of TLR-4 as well as the N5: CC-genotype (O.R.=2.830, p = 0.031), N6: AA-genotype (O.R.=2.6, p = 0.0122) and 'A'-allele (O.R.=1.746, p = 0.0064), N7:CC-genotype (O.R.2.706, p = 0.0111) and 'C'-allele (O.R. 1.774, p = 0.0055) of TLR-9 were correlated with GIGR and BI. TLR-4 (N1-N2-N3-N4: A-C-T-A (O.R.=2.1, p = 0.0069) and TLR-9 (N5-N6-N7-N8: T-A-C-A (O.R.=2.019, p = 0.0263); C-A-C-A (O.R.=6.0, p = 0.0084); C-A-C-G (O.R.=4.957, p = 0.0452) haplotypes were linked with OSCC vulnerability, while the TLR-4 (N1-N2-N3-N4: G-C-C-A (O.R.=0.5752, p = 0.0131) and TLR-9 (N5-N6-N7-N8: T-G-T-A (O.R.=0.5438, p = 0.0314); T-G-T-G (O.R.=0.5241, p = 0.036) haplotypes offered protection. CONCLUSION: TLR-4/9 expression, polymorphisms, and BI-induced GIGR could increase OSCC risk. This may be used in pathogenesis and oral cancer prediction.

Visible-Light-Mediated Synthesis of Phenanthrenes through Successive Photosensitization and Photoredox by a Single Organocatalyst.

An efficient approach for the synthesis of phenanthrene scaffolds by utilizing the dual catalytic activity of an organo-photocatalyst is documented. The controlled cascade transformation proceeds via in situ diazotization followed by olefin isomerization and subsequent arene radical generation through photoreduction. The overall process demonstrates both the photosensitization and photoredox properties of a single organo-photocatalyst and facilitates the desired intramolecular annulation with high precision and efficacy. In this context, the underexplored organocatalyst acridine orange base is employed and the photophysical interactions between the catalyst and the substrates along with the detailed reaction kinetics are documented.

"Oxygen Pheriwala:" An innovative model for SARS-CoV-2 screening in resource-limited settings.

The second wave of SARS-CoV-2 infection came as a hypoxic emergency and situation became worse in rural India, where undiagnosed COVID-19 patients died without any diagnosis or intervention. The primary aim of this innovative model was the early diagnosis of suspected SARS-CoV-2 cases, providing empirical treatment and timely referral to appropriate COVID care facilities. Fever was measured with infrared thermometer and oxygen saturation level with pulse oximeter. A total of 8203 people were screened, of which 274 persons were febrile and 69 (25%) were hypoxic too. Sixty-four out of 69 (93%) patients turned COVID-19 positive on reverse transcription-polymerase chain reaction. At the end of 3 weeks, 48/64 (75%) patients were successfully discharged. This model can be easily implemented in resource-limited regions to identify and prioritize the patients not only in this pandemic but also in outbreak of other communicable diseases.

Impact of SARS-CoV-2 Pandemic on Glycaemic Control, Metabolic Status, Treatment Adherence, Quality of Life in Diabetes Mellitus Patients in Tertiary Care Hospital of Eastern India.

Introduction: Many medical and social challenges have been noticed during lockdowns and restrictions in the course of the COVID-19 pandemic. These restrictions had a profound impact on people's lifestyle and caused psychological distress. In the management of type 2 diabetes mellitus, lifestyle modifications, such as nutritional intervention and proper physical activity, are important aspects. Aims/objective:To study the effect of lockdown or self-imposed restrictions due to pandemic on glycaemic control in diabetes mellitus patients and the possible determinants, including diet, sleep, physical activity, psychological status and adherence to treatment. Materials and methods:A comparative analysis of the glycaemic status and metabolic parameters (such as random blood glucose, glycated haemoglobin, weight, hypoglycaemia and lipid profile), lifestyle and psychological changes and treatment adherence was done in 103 patients. Retrospective pre-lockdown data was collected from the clinical records and interviews (offline, online or by telephone). Prospective lockdown/restrictions data was questionnaire based. Chi-square test was used to analyse categorical data and ANOVA for continuous data. Results:The majority of patients were in the age group of 40-60 years. Most of them reported disturbance in their adherence to proper diet, physical activity, sleep and medication schedule. These differences of opinion were statistically significant (p <0.00001). There were more patients who reported stress and anxiety and this difference was statistically significant. Deterioration of glycaemic control and lipid profile was highly significant (p <0.00001). Mean body weight was increased by 6.67% at the end of the study and the difference was statistically significant. Conclusion:In patients with diabetes, pandemic-related restrictions had a profound impact on the glycaemic control, metabolic status, adherence to medication and quality of life. This highlights the need for a multidisciplinary approach in managing patients with diabetes, focusing on various issues, including prevalence of poor diet control, physical inactivity and psychological stress, via various awareness and counselling programs, preferably through online mode.

Identification of Epigenetically Modified Hub Genes and Altered Pathways Associated With Retinoblastoma.

Retinoblastoma (Rb) is the most common childhood malignancy initiated by biallelic mutation in RB1 gene and driven by various epigenetic events including DNA methylation and microRNA dysregulation. Hence, understanding the key genes that are critically modulated by epigenetic modifications in RB1 -/- cells is very important to identify prominent biomarkers and therapeutic targets of Rb. In this study, we for the first time have integrated various Rb microarray NCBI-GEO datasets including DNA Methylation (GSE57362), miRNA (GSE7072) and mRNA (GSE110811) to comprehensively investigate the epigenetic consequences of RB loss in retinoblastoma tumors and identify genes with the potential to serve as early diagnostic markers and therapeutic targets for Rb. Interestingly, the GEO2R and co-expression network analysis have identified three genes namely E2F3, ESR1, and UNC5D that are significantly deregulated by modified DNA methylation, mRNA and microRNA expression in Rb tumors. Due to their recognition in all epigenetic, transcriptomic, and miRNA datasets, we have termed these genes as "common genes". The results of our integrative bioinformatics analysis were validated in vitro by studying the gene and protein expression of these common genes in Y79, WERI-Rb-1, Rb cell lines and non-tumorigenic retinal pigment epithelial cell line (hTERT-RPE). The expression of E2F3 and UNC5D were up-regulated and that of ESR1 was down-regulated in Rb tumor cells when compared to that in non-tumorigenic hTERT-RPE cells. More importantly, UNC5D, a potent tumor suppressor gene in most cancers is significantly up-regulated in Y79 and Weri Rb1 cells, which, in turn, questions its anti-cancer properties. Together, our study shows that E2F3, ESR1, and UNC5D may be crucially involved in Rb tumorigenesis and possess the potential to act as early diagnostic biomarkers and therapeutic targets of Rb.