Aqueous Graphene Dispersion and Biofunctionalization via Enzymatic Oxidation of Tripeptides.

Graphene, a 2D carbon material, possesses extraordinary mechanical, electrical, and thermal properties, making it highly attractive for various biological applications such as biosensing, biotherapeutics, and tissue engineering. However, the tendency of graphene sheets to aggregate and restack hinders its dispersion in water, limiting these applications. Peptides, with their defined amino acid sequences and versatile functionalities, are compelling molecules with which to modify graphene-aromatic amino acids can strengthen interactions through π-stacking and charged groups can be chosen to make the sheets dispersible and stable in water. Here, a facile and green method for covalently functionalizing and dispersing graphene using amphiphilic tripeptides, facilitated by a tyrosine phenol side chain, through an aqueous enzymatic oxidation process is demonstrated. The presence of a second aromatic side chain group enhances this interaction through non-covalent support via π-π stacking with the graphene surface. Futhermore, the addition of charged moieties originating from either ionizable amino acids or terminal groups facilitates profound interactions with water, resulting in the dispersion of the newly functionalized graphene in aqueous solutions. This biofunctionalization method resulted in ≈56% peptide loading on the graphene surface, leading to graphene dispersions that remain stable for months in aqueous solutions outperforming currently used surfactants.

Molecular cloning, biophysical and in silico studies of Human papillomavirus 33 E2 DNA binding domain.

Human papillomavirus 33, a high-risk HPV strain, is mainly responsible for HPV infection and cervical cancer in Asian countries. The E2 protein of HPV 33 is a DNA-binding protein that plays a crucial role in viral replication and transcription. We have cloned, overexpressed, and purified the DNA binding domain of the E2 protein. Size exclusion chromatography results suggested that the protein exists in a homodimeric state in the native form. Circular dichroism data showed that the protein has a higher content of ß-sheet. The melting temperature obtained from differential scanning calorimetry is 52.59 °C, and the protein is stable at pH 8 and is in a dimeric form at basic pH. The protein is monomeric or unfolded at a very low pH. Chemical denaturation studies suggested that the protein denatured and dissociated simultaneously. The DNA binding activity of the protein was also confirmed and it showed binding affinity in the order of 106 M-1. The protein structure was modeled using homology modeling and other bioinformatic tools. The virtual screening and molecular dynamic simulation studies were performed to find compounds that can act as potent inhibitors against E2 DBD. This study expands the understanding of the conserved structural and binding properties of HPV33 E2 DBD and provides the first report on the characterization of the viral protein.Communicated by Ramaswamy H. Sarma.

Investigation, scaffold hopping of novel donepezil-based compounds as anti-Alzhiemer's agents: synthesis, in-silico and pharmacological evaluations.

Alzheimer's disease (AD) is a multifaceted neurodegenerative condition. The pathogenesis of AD is highly intricate and the disease is apparent in the aged population ~ 50-70 years old. Even after > 100 years of research, the root origin of AD and its pathogenesis is unclear, complex and multifaceted. Herein, we have designed and synthesized 9 novel molecules with three different heterocyclic scaffolds namely pyrrolidone-2-one, quinoline & indoline-2-one to imitate and explore the novel chemical space around donepezil. The synthesized molecules were evaluated for their potential as anti-Alzheimer's agents through in-vitro and in-vivo studies in appropriate animal models. To further understand their interaction with acetylcholinesterase enzyme (AChE), extra-precision docking, and molecular dynamics simulation studies were carried out. As the number of compounds was limited to thoroughly explore the structure-activity relationship, atom-based 3D-quantitative structure-activity relationships (QSAR) studies were carried out to get more insights. All the designed compounds were found to inhibit AChE with IC50 in the micromolar range. From pyrrolidone-2-one series, 6-chloro-N-(1-(1-(3,4-dimethoxybenzyl)-2-oxopyrrolidin-3-yl)piperidin-4-yl)pyridine-3-sulfonamide (9), 2-(1-benzylpiperidin-4-yl)-6,7-dimethoxy-4-(4-methoxyphenyl)quinoline (18) from quinoline series and N-(1-benzylpiperidin-4-yl)-2-(2-oxoindolin-3-yl)acetamide (23) from indolin-2-one series inhibited AChE with an IC50 value of 0.01 µM. Based on other biochemical studies like lipid peroxidation, reduced glutathione, superoxide dismutase, catalase, nitrite, and behavioural studies (Morris water maze), compound 9 was found to be a potent AChE inhibitor which can be further explored as a lead molecule to design more potent and effective anti-Alzheimer's agents.

Disrupted brain mitochondrial morphology after in vivo hydrogen sulfide exposure.

Changes in mitochondrial dynamics are often associated with dietary patterns, medical treatments, xenobiotics, and diseases. Toxic exposures to hydrogen sulfide (H2S) harm mitochondria by inhibiting Complex IV and via other mechanisms. However, changes in mitochondrial dynamics, including morphology following acute exposure to H2S, are not yet fully understood. This study followed mitochondrial morphology changes over time after a single acute LCt50 dose of H2S by examining electron microscopy thalami images of surviving mice. Our findings revealed that within the initial 48 h after H2S exposure, mitochondrial morphology was impaired by H2S, supported by the disruption and scarcity of the cristae, which are required to enhance the surface area for ATP production. At the 72-h mark point, a spectrum of morphological cellular changes was observed, and the disordered mitochondrial network, accompanied by the probable disruption of mitophagy, was tied to changes in mitochondrial shape. In summary, this study sheds light on how acute exposure to high levels of H2S triggers alterations in mitochondrial shape and structure as early as 24 h that become more evident at 72 h post-exposure. These findings underscore the impact of H2S on mitochondrial function and overall cellular health.

Insights into the mechanism of binding of doxorubicin and a chlorin compound with 22-mer c-Myc G quadruplex.

BACKGROUND: The interaction of small molecules with G quadruplexes is in focus due to its role in molecular recognition and therapeutic drug design. Stabilization of G-quadruplex structures in the promoter regions of oncogenes by small molecule binding has been demonstrated as a potential approach for cancer therapy. METHODS: In this study, electronic spectroscopy (ultraviolet-visible, fluorescence, circular dichroism), differential scanning calorimetry, and molecular modeling were employed to explore the interactions between the chemotherapy drug doxorubicin and a chlorin compound 5,10,15,20-tetraphenyl-[2,3]-[bis(carboxy)-methano]chlorin (H2TPC(DAC)), and the c-Myc 22-mer G quadruplex DNA. RESULTS: Spectroscopic studies indicated external binding of the compounds with partial stacking at the end quartets. Calorimetric studies and temperature dependent circular dichroism data displayed increased melting temperatures of G quadruplex structure on binding with the compounds. Circular dichroism spectra indicated that the G quadruplex structure is intact upon ligand binding. Both the compounds showed binding affinities of the order of 106 M-1. Fluorescence lifetime studies revealed static quenching as major mechanism for fluorescence quenching. Polymerase chain reaction stop assay hinted that binding of both ligands under study could inhibit the amplification of the DNA sequence. CONCLUSION: Results show that doxorubicin and H2TPC(DAC) bind to the 22-mer c-Myc quadruplex structure with good affinity and induce stability. SIGNIFICANCE: Doxorubicin and H2TPC(DAC) have demonstrated their affinity towards c-Myc G quadruplex DNA, stabilizing it and inhibiting expression and polymerization. The results can be of practical use in designing new analogs for the two compounds, which can become potent anti-cancer agents targeting the c-Myc GQ structure.

An optimized approach towards bio-capture and carbon dioxide sequestration with microalgae Phormidium valderianum using response surface methodology.

As carbon dioxide emissions rise, there's need for alternative strategies, including microorganisms, to capture and mitigate them. The present study investigated on the capability and tolerance of microalgal strain, Phormidium valderianum to capture gaseous CO2 at varying levels (5-30 %). A biomass productivity of 0.0216 ± 0.027 gL-1day-1 and rate of CO2 fixation of 0.035 gL-1day-1 was obtained for 25 % CO2 concentration. From this study, it is evident that higher CO2 levels led to elevated carbohydrate concentration. In addition, protein concentration doubled with the introduction of 25 % CO2. In optimization studies, pH 10, 25 % CO2, and 200 mg/L of Ca(OH)2 concentration was found to be optimal for biomass growth. A higher rate of CO2 fixation of 0.315 gL-1day-1 was achieved at these optimum conditions using response surface methodology. Furthermore, the study demonstrated that microalgae, Phormidium valderianum has the potential to serve as a promising alternative for capturing CO2 emissions.

Synthesis, characterization, and in silico studies of 1,8-naphthyridine derivatives as potential anti-Parkinson's agents.

1,8-Naphthyridine scaffold is a nitrogen-containing heterocyclic compound known for its versatile biological activities. The structure-activity relationship (SAR) has shown that modification at the 3rd position of the nucleus with various secondary amines enhances the binding efficiency and potency towards the Adenosine receptor (A2A type). In this paper, we have reported some newly synthesized derivatives of 1,8- Naphthyridine, and the prepared compounds were assessed for their potential to constrain A2A receptors through molecular docking. Based on the SAR studies, modifications were done at the 3rd position of the nucleus by incorporating secondary amines. The synthesized compounds were characterized by FT-IR, 1H and 13C NMR. All the synthesized compounds 10a-f and 13a-e showed good binding efficiency towards the A2A receptors and might act as an A2A receptor antagonist, as predicted by in-silico studies. 1-Ethyl-7-methyl-3-(pyrrolidine-1-carbonyl)-1,8-naphthyridine-4(1H)-one (10c) in first series showed the highest docking score of -8.407 and binding energy (MMGBSA dG bind) of -56.60 kcal/mol and N-(4-2-diethylaminoethoxyphenyl)-1-ethyl-7-methyl-4-oxo-1, 4, 4a, 8a- tetrahydro-1,8-naphthyridine-3-carboxamide (13b) showed the highest docking score of -8.562 and free binding energy (MMGBSA dG bind) score of -64.13 kcal/mol which was comparable to the bound ligand. MD simulations study also suggested that compounds 10c and 13b would form stable complex human A2A receptor. These findings need to be validated by further in vitro assays.Communicated by Ramaswamy H. Sarma.

Design, synthesis, extra-precision docking, and molecular dynamics simulation studies of pyrrolidin-2-one derivatives as potential acetylcholinesterase inhibitors.

Inhibition of acetylcholinesterase (AChE) has been widely explored to develop novel molecules for management of Alzheimer's disease. In past research finding reported molecule 3-(4-(4-fluorobenzoyl)piperidin-1-yl)-1-(4-methoxybenzyl)pyrrolidin-2-one displayed a spectrum of anti-Alzheimer's properties herein, we report a library of 18 novel molecules that were rationally designed and synthesized employing known literature to mimic and explore the novel chemical space around the lead compound 6e and donepezil. All the compounds were docked in extra-precision mode with AChE (PDB ID 4EY7) using the Glide module. Molecular dynamics (MD) simulation studies were carried out for 100 ns along with MM-PBSA studies of the trajectory frames generated post-MD simulations. Docking and MD simulation studies suggested that the synthesized compounds showed a good binding affinity with AChE. and might form stable complexes. 3-(4-(benzyl(methyl)amino)piperidin-1-yl)-1-(3,4-dimethoxybenzyl)pyrrolidin-2-one (14a; docking score: -18.59) and 1-(3,4-dimethoxybenzyl)-3-(4-(methyl(thiazol-2-ylmethyl)amino)piperidin-1-yl)pyrrolidin-2-one (14d; docking score: -18.057) showed higher docking score than donepezil (docking score: -17.257) while most of the compounds had docking score >-10.0. ADMET study predicted these compounds to be CNS active and most of the compounds were drug-like molecules with no HERG blockade and good to excellent oral absorption. We developed an atom-based 3 D-QSAR model with R^2 and Q^2 values of 0.9639 and 0.8779 to predict the activity of the synthesized compounds. The model predicted these compounds to be potent AChE inhibitors with IC50 values in the lower micromolar range. Based on the in silico findings, we report these newly synthesized compounds 3-(4-(benzyl(methyl)amino)piperidin-1-yl)-1-(3,4-dimethoxybenzyl)pyrrolidin-2-one (14a) and 7-(2,6-difluorobenzyl)-2-(4-methoxybenzyl)-2,7-diazaspiro[4.5]decan-1-one (20 b) as potential AChE inhibitors.Communicated by Ramaswamy H. Sarma.

An insight into the pharmacological and analytical potential of Andrographolide.

Andrographis paniculata is an annual medicinal herb from the family Acanthaceae. Andrographolide is generally considered an essential bioactive component of plant A. paniculata. Since ancient times, it has been widely recognized for its therapeutic qualities and has attracted the scientific and medical communities' attention. This review summarizes the molecular, clinical, and in vitro research of compound andrographolide and its mechanism of action. Andrographolide, when combined with other enhancing agents, offers a wide variety of health benefits. The therapeutic potential of andrographolide has been exemplified and exhibited by directly regulating genes and indirectly interacting with small molecules and different enzymes. This review compiles and consolidates the pharmacological action of andrographolide and its analogs and deciphers the gaps that have hindered its use in medicinal research.

Breakdown of Universal Scaling for Nanometer-Sized Bubbles in Graphene.

We report the formation of nanobubbles on graphene with a radius of the order of 1 nm, using ultralow energy implantation of noble gas ions (He, Ne, Ar) into graphene grown on a Pt(111) surface. We show that the universal scaling of the aspect ratio, which has previously been established for larger bubbles, breaks down when the bubble radius approaches 1 nm, resulting in much larger aspect ratios. Moreover, we observe that the bubble stability and aspect ratio depend on the substrate onto which the graphene is grown (bubbles are stable for Pt but not for Cu) and trapped element. We interpret these dependencies in terms of the atomic compressibility of the noble gas as well as of the adhesion energies between graphene, the substrate, and trapped atoms.

Comparison of the Efficacy of K-File, Canal Brush Technique, and Sonic Irrigation Technique in the Retrievability of Calcium Hydroxide and Metapex Intracanal Medicaments from Root Canals: An In vitro Cone-Beam Computed Tomography Analysis.

BACKGROUND AND OBJECTIVES: At present, none of the routinely used irrigating agents and activation techniques were able to completely remove the Ca(OH)2 intracanal medicament placed inside the root canal system during endodontic therapy. With this as the background, the aim of this study was to achieve complete removal of Ca(OH)2 when mixed with two different vehicles, using various irrigant activation techniques such as K-file, canal brush technique, and sonic irrigation technique, from the root canals of extracted human teeth. MATERIALS AND METHODS: Seventy-two mandibular premolar teeth with straight single root canal were selected and filled either with oil-based Metapex or calcium hydroxide powder mixed with distilled water and were activated using different activation techniques such as K-file, canal brush, and sonic MM1500 and NaOCl alone. Volumetric analysis was performed utilizing cone-beam computed tomography. RESULTS: None of the irrigants used were able to completely remove Ca(OH)2 from root canal. Sonic MM1500 showed significant removal efficacy than K-file, canal brush technique, and NaOCl for both aqueous-based and oil-based calcium hydroxide. CONCLUSION: Sonic MM1500 performed better than K-file, canal brush technique, and NaOCl in removing both Metapex and Ca(OH)2 powder. Regardless of the vehicles and agitation technique used, the remnants of Ca(OH)2 were present on all thirds of the canal walls.

Exploring the binding of resveratrol to a promoter DNA sequence d(CCAATTGG)2 through multispectroscopic, nuclear magnetic resonance and molecular dynamics studies.

We report the interaction of resveratrol with an octamer DNA sequence d(CCAATTGG)2, present in the promoter region of many oncogenes, using a combination of absorption, fluorescence, calorimetric and nuclear magnetic resonance techniques to probe the binding. Resveratrol binds to the duplex sequence with a binding constant 2.20 × 106 M-1 in absorption studies. A ligand-duplex stoichiometry of 2.2:1 was obtained with binding constant varying from 103 to 104 M-1 in fluorescence titration measurements. Spectral changes indicated external binding of resveratrol to duplex DNA. Circular dichroism data displayed minimal variation suggesting external binding. Melting temperatures of DNA and its 1:1 complex showed a difference of approximately 2.25 °C, supporting the external binding. Nuclear magnetic resonance data showed resveratrol binds to the minor groove region near the AT base pair from the nuclear Overhauser effect spectroscopic cross peaks. Distance restrained molecular dynamics was employed in explicit solvent condition to obtain the lowest energy structure. The complex was stable and retained the B DNA conformation. Findings in this study identify resveratrol as a minor groove binder to the AT region of DNA and pave the way for exploring resveratrol and its analogues as promising anticancer/antibacterial drug.

Doping Graphene with Substitutional Mn.

We report the incorporation of substitutional Mn atoms in high-quality, epitaxial graphene on Cu(111), using ultralow-energy ion implantation. We characterize in detail the atomic structure of substitutional Mn in a single carbon vacancy and quantify its concentration. In particular, we are able to determine the position of substitutional Mn atoms with respect to the Moiré superstructure (i.e., local graphene-Cu stacking symmetry) and to the carbon sublattice; in the out-of-plane direction, substitutional Mn atoms are found to be slightly displaced toward the Cu surface, that is, effectively underneath the graphene layer. Regarding electronic properties, we show that graphene doped with substitutional Mn to a concentration of the order of 0.04%, with negligible structural disorder (other than the Mn substitution), retains the Dirac-like band structure of pristine graphene on Cu(111), making it an ideal system in which to study the interplay between local magnetic moments and Dirac electrons. Our work also establishes that ultralow-energy ion implantation is suited for substitutional magnetic doping of graphene. Given the flexibility, reproducibility, and scalability inherent to ion implantation, our work creates numerous opportunities for research on magnetic functionalization of graphene and other two-dimensional materials.

Elucidating the Drug Repurposing Spectra of COVID-19 with its Analogues SARS and MERS.

Corona Virus Disease-2019 (COVID-19), caused by the SARS CoV-2 virus, has been announced as a pandemic by the World Health Organization. COVID-19 has affected people globally, infecting more than 39.8 million people and claiming up to 1.11 million lives, yet there is no effective treatment strategy to cure this disease. As vaccine development is a time-consuming process, currently, efforts are being made to develop alternative plans for the timely and effective management of this disease. Drug repurposing always fascinated researchers and can be utilized as the most acceptable alternative to develop the therapeutics for COVID-19 using the pre-approved drugs. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has shown resemblance with distinctive enzyme targets, such as 3CLpro/Mpro, RdRp, Cathepsin L, and TMPRSS2 present in SARS CoV and MERS CoV. Therefore, the drugs that have shown efficacy in these viruses can also be used for the treatment of COVID-19. This review focuses on why repurposing could provide a better alternative in COVID- 19 treatment. The similarity in the structure and progression of infection of SARS CoV and MERS viruses offers a direction and validation to evaluate the drugs approved for SARS and MERS against COVID-19. It has been indicated that multiple therapeutic options that demonstrate efficacy against SARS CoV 2 are available to mitigate the potential emergence of COVID-19 infection.

Deciphering the interaction of flavones with calf thymus DNA and octamer DNA sequence (CCAATTGG)2.

We investigated the interaction of three flavone compounds, baicalein, chrysin and flavone with calf thymus DNA and octamer DNA sequence (CCAATTGG)2. The binding mechanisms of the flavone compounds with both DNA were unveiled using biophysical, thermodynamic and molecular modelling techniques. Absorption and fluorescence titrations confirm the formation of the DNA complexes along with the extent of interaction. Absorption data proposed an intercalation mode of binding. Fluorescence displacement assays using ethidium bromide and Hoechst 33258 data supports a partial intercalation. Potassium iodide quenching substantiated this finding. Circular dichroism data revealed major structural changes on binding with flavones which can arise from intercalation partially or in a tilted arrangement. Analysis of the effect of ionic strength on complex formation eliminated the role of electrostatic interaction in the binding. Differential scanning calorimetric data showed substantial changes in the melting temperatures of complexes and predicted the DNA-baicalein complex as the most stable one. Molecular modelling showcased that the complexes are located near the AT rich region. Docking analysis with different sequences showed that the flavone compounds intercalated with base pairs only with d(CGATCG)2.

Molecular modeling, simulation and principal component analysis of binding of resveratrol and its analogues with DNA.

Structure-based drug designing has become a significant subject of research, and several clinically promising DNA binding compounds were evolved using this technique. The interaction of an octamer DNA sequence d(CCAATTGG)2 with a natural stilbene, resveratrol and its analogues have been studied using molecular docking method. Out of the ten compounds studied, seven compounds were found to bind to the minor groove of AATT segment of the sequence. Pterostilbene, a natural analogue of resveratrol, showed the lowest binding energy. Rhaponticin, a natural analogue of resveratrol and digalloylresveratrol, a synthetic ester of resveratrol bind to the major groove of the AATT segment while dihydroresveratrol binds to the minor groove of GC terminal base pair. ADMET (Absorption, distribution, metabolism, excretion and toxicity) study showed that all compounds obey Lipinski rule and are accepted as orally active drugs based on different physicochemical descriptors. Molecular dynamics simulations were performed for the complex with lowest binding energy and trajectory analysis were performed. Principal component analysis has been performed to underline the prominent motions in alone DNA and when it is bound to pterostilbene. AbbreviationsADMETAbsorption, distribution, metabolism, excretion and toxicityDIGDigalloyl resveratrolDNADeoxyribonucleic acidELElectrostatic energyENPOLARNonpolar solvation energyESURFSurface areaGBGeneralized BornHBAHydrogen bond acceptorsHBDHydrogen bond donorsLGALamarckian genetic algorithmMDMolecular dynamicsPBPoisson-BoltzmannPCAPrincipal component analysisPTPterostilbeneRMSDRoot mean square deviationSASimulated annealingTLX3T-cell leukemia homeobox 3VDWvan der WaalsCommunicated by Ramaswamy H. Sarma.

Pancreatic Cancer: An Emphasis on Current Perspectives in Immunotherapy.

Pancreatic cancer affects both male and female individuals with higher incidences and death rates among the male population. Detection of this malignancy is delayed due to the lack of symptoms in the early-stage cancer, which makes it extremely difficult to treat. Identifying effective strategies has been a challenge for improving the survival rates in pancreatic cancer patients. Resistance to chemotherapy is often developed in pancreatic cancer treatment. Although many strategies are under clinical trials to target certain markers associated with cancer, immunotherapeutic approaches are currently gaining importance. Immunotherapy for pancreatic cancer is in the limelight after preclinical research showed some promise. Immunotherapy approaches were tested along with other treatment options to enhance the treatment effect. Adoptive cell transfer and immune checkpoint inhibitors are currently in clinical trials. The Food and Drug Administration approved pembrolizumab in a fast-tracked review for advanced pancreatic cancer patients. Pembrolizumab blocks the checkpoint protein, programmed cell death protein 1 (PD-1), on T cells to boost the response of the immune system against cancer cells, thereby shrinking tumors. The recent developments in immunotherapy and the early success in other cancers are encouraging to further test immunotherapy in pancreatic cancer. The combination of pembrolizumab and pelareorep, an isolate of human reovirus, is in phase II clinical study in metastatic disease. Depending on the results of current clinical trials and testing, the strategies in the pipeline are expected to increase the use of immunotherapy in the clinical testing setting. Success in immunotherapy is urgently needed to address the side-effects, treating patients with advanced disease and reducing metastasis for increasing the survival rate in pancreatic cancer patients.

Ovarian cancer: Current status and strategies for improving therapeutic outcomes.

Of all the gynecologic tumors, ovarian cancer (OC) is known to be the deadliest. Advanced-stages of OC are linked with high morbidity and low survival rates despite the immense amount of research in the field. Shortage of promising screening tools for early-stage detection is one of the major challenges linked with the poor survival rate for patients with OC. In OC, therapeutic management is used with multidisciplinary approaches that includes debulking surgery, chemotherapy, and (rarely) radiotherapy. Recently, there is an increasing interest in using immunomodulation for treating OC. Relapse rates are high in this malignancy and averages around every 2-years. Further treatments after the relapse are more intense, increasing the toxicity, resistance to chemotherapy drugs, and financial burden to patients with poor quality-of-life. A procedure that has been studied to help reduce the morbidity rate involves pre-sensitizing cancer cells with standard therapy in order to produce optimal results with minimum dosage. Utilizing such an approach, platinum-based agents are effective due to their increased response to platinum-based chemotherapy in relapsed cases. These chemo-drugs also help address the issue of drug resistance. After conducting an extensive search with available literature and the resources for clinical trials, information is precisely documented on current research, biomarkers, options for treatment and clinical trials. Several schemes for enhancing the therapeutic responses for OC are discussed systematically in this review with an attempt in summarizing the recent developments in this exciting field of translational/clinical research.

An Institutional Coordinated Plan for Effective Partnerships to Achieve Health Equity and Biomedical Workforce Diversity.

The rapid growth and accumulation of specialized knowledge in today's biomedical fields, combined with entrenched and emerging health issues that persist among certain groups within the US population, emphasizes the significant need to diversify the nation's biomedical science workforce. The under-representation of minorities in science results in inadequate scientific input from divergent social or cultural perspectives and detracts from our nation's ability to resolve health disparities. The University of North Texas Health Science Center at Fort Worth has developed a coordinated approach with local, regional, and national partners to increase participation of underrepresented students along the career pathway from K-12 to faculty level. Career stage specific activities that include research, mentoring, networking, career development, grantsmanship and health disparities curriculum are provided for participants. Successful outcomes from our coordinated plan includes an increase in participant self-efficacy, research presentation awards, increase in grant awards and publications, and career advancement. Through partnerships within our institution, local school districts, and minority serving institutions nationwide, our coordinated plan provides mutually beneficial co-learning experiences to increase the number of under-represented individuals entering translational research focused on increasing the biomedical research workforce diversity and achieving health equity.