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Abstract Derangements in protein homeostasis and associated proteotoxicity mark acute, chronic, and drug-induced hepatocellular injury. Metabolic dysfunction-associated proteasomal inhibition and the use of proteasome inhibitors often underlie such pathological hepatic proteotoxicity. In this study, we sought to identify a candidate deubiquitinating enzyme (DUB) responsible for reversing the proteotoxic damage. To this end, we performed a siRNA screening wherein 96 DUBs were individually knocked down in HepG2 cells under proteasomal inhibitor-induced stress for dual readouts, apoptosis, and cell viability. Among the putative hits, we chose JOSD1, a member of the Machado-Josephin family of DUBs that reciprocally increased cell viability and decreased cell death under proteotoxicity. JOSD1-mediated mitigation of proteotoxicity was further validated in primary mouse hepatocytes by gain and loss of function studies. Marked plasma membrane accumulation of monoubiquitinated JOSD1 in proteotoxic conditions is a prerequisite for its protective role, while the enzymatically inactive JOSD1 C36A mutant was conversely polyubiquitinated, does not have membrane localisation and fails to reverse proteotoxicity. Mechanistically, JOSD1 physically interacts with the suppressor of cytokine signalling 1 (SOCS1), deubiquitinates it and enhances its stability under proteotoxic stress. Indeed, SOCS1 expression is necessary and sufficient for the hepatoprotective function of JOSD1 under proteasomal inhibition. In vivo, adenovirus-mediated ectopic expression or depletion of JOSD1 in mice liver respectively protects or aggravates hepatic injury when challenged with proteasome blocker Bortezomib. Our study thus unveils JOSD1 as a potential candidate for ameliorating hepatocellular damage in liver diseases.

Abstract Coronavirus with intact infectivity attached to PPE surfaces pose significant threat to the spread of COVID-19. We tested the hypothesis that an electroceutical fabric, generating weak potential difference of 0.5 V, disrupts the infectivity of coronavirus upon contact by destabilizing the electrokinetic properties of the virion. Porcine respiratory coronavirus AR310 particles (105) were placed in direct contact with the fabric for 1 or 5 min. Following one minute of contact, zeta potential of the porcine coronavirus was significantly lowered indicating destabilization of its electrokinetic properties. Size-distribution plot showed appearance of aggregation of the virus. Testing of the cytopathic effects of the virus showed eradication of infectivity as quantitatively assessed by PI-calcein and MTT cell viability tests. This work provides the rationale to consider the studied electroceutical fabric, or other materials with comparable property, as material of choice for the development of PPE in the fight against COVID-19.

In recent days, the utilization of lightweight alloys for various applications has been increased massively. Starting from the automobile industry, aerospace industry, and even in the biomedical field, there is a need for dissimilar precise joining of steel to other light alloys (magnesium alloy, aluminum alloy, titanium alloy). However, those alloys are characterized by different melting temperatures, machinability, strength, thermal conductivity, and oxygen reactivity. Considering this welding to challenge ongoing laser welding efforts to improve laser welding quality by altering the welding techniques, modes, proper use of shielding gasses, using suitable process parameters, and even proper joint and surface preparations are discussed. The feasibility of implementing all those things in the industrial setup can be understood only after analyzing recent works. Changes in microstructure and the defects (solidification cracking, intermetallic components formation, porosity) arrived during and after laser welding of these materials are reviewed. The paper also highlights the effect of shielding gas, welding speed, laser power, defocusing position, etc. during laser welding of lightweight materials. The critical issues related to dissimilar laser welding of these combinations and some remedial measures are discussed. The purpose of this review is to emphasize and understand the recent trends of dissimilar laser welding and explore the scope of industry level applications.

Aims: Obesity associated prolonged hyperinsulinemia followed by β-cell failure is well established as the pathology behind type 2 diabetes mellitus (T2DM). However, studies on nonobese T2DM have reported it to be a distinct clinical entity with predominant insulin secretory defect. We, therefore, hypothesized that compensatory hyperinsulinemia in response to weight gain is impaired in nonobese subjects. Methods: This was a cross-sectional study from a community-based metabolic health screening program. Adiposity parameters including body mass index (BMI), waist circumference (WC), body fat percentage, plasma leptin concentration and metabolic parameters namely fasting insulin, glucose, total cholesterol, and triglycerides were measured in 650 individuals (73% healthy, 62% nonobese with a BMI

Distribution of temperature during the welding process is essential for predicting and realizing some important welding features such as microstructure of the welds, heat-affected zone (HAZ), residual stresses, and their effects. In this paper, a numerical model was developed using COMSOL Multiphysics of dissimilar laser welding (butt joint) of AISI 316L and Ti6Al4V thin sheet of 2.5 mm thickness. A continuous mode (CW) fiber laser heat source of 300 W laser power was used for the present study. A time-dependent prediction of temperature distributions was attempted. The heat source was assumed as a Hermit–Gaussian analytical function with a moving velocity of 120 mm/min. Both convective and radiant heat loss and phase change of the materials were considered for the analysis. In addition, variation of temperature-dependent material properties was also considered. The maximum and minimum temperature for the two materials at different times and the temperature in the different penetration depths were also predicted. It was found that the average temperature that can be achieved in the bottom-most surface near the weld line was more than 2400 K, which justifies the penetration. Averages of maximum temperatures on the weld line at different times at the laser spot irradiation were identified near 3000 K.The temperature fluctuation near the weld line was minimal and decreased more in the traverse direction. Scanning with a displaced laser relative to the interface toward the Ti6Al4V side reduces the maximum temperature at the interface and the HAZ of the 316L side. All of these predictions agree well with the experimental results reported in current literature studies.

Background: Antibiotic resistance in healthcare system is a widespread and inevitable problem which is mainly due to their inappropriate and indiscriminate prescribing or use. The misuse of antibiotics which is having substantial detrimental consequences is under the influence of clinicians’ education, existing beliefs, incentives offered by the pharmaceutical manufacturers, hospital’s sales profit and usual trend among the prescribers to use antimicrobials haphazardly. Objectives: The objective of the study was to determine the pattern of bacterial culture sensitivity and antimicrobials prescribing. Material and Methods: The study was a retrospective cross-sectional analysis of culture sensitivity reports for duration of 5 months (May to September 2010) at the laboratory of department of microbiology, Nobel Medical College and Research Centre, Biratnagar Nepal. Data was collected through a self designed and pre-piloted questionnaire. The questionnaire contained information on patient’s particulars, diagnosis, specimen, culture sensitivity and antimicrobials prescribed before performing culture sensitivity tests. Patient’s names and hospital Identification number were noted from the register and their respective prescriptions were investigated from medical record department of the hospital. The prescriptions were analyzed for the antimicrobials prescribed before carrying out culture sensitivity tests. The data was coded, verified, entered and analyzed using Statistical Package for Social Sciences version 11.5 Chicago, Inc. Results: Majority (71%) of the patients were below the age of 30 years. Diagnosis of the disease was not mentioned in majority (88%) of the reports. Staphylococcus aureus and Escherichia coli were the most commonly occurring bacteria (78%). Treating infectious complications with single antimicrobial agent was predominant (68%). Furthermore, third generation cephalosporins (47%) particularly ceftriaxone and cefotaxime were the most commonly prescribed agents, but culture sensitivity was not performed against them. There was a striking practice of prescribing antimicrobials against the bacteria which were either resistant or culture sensitivity was not performed. Conclusion: Bacterial resistance and inappropriate prescribing of antimicrobials are important issues at Nobel teaching hospital which entails expanding antimicrobial susceptibility testing to commonly used or prescribed antimicrobials

Introduction: The soil-transmitted helminthiases (STH) are important neglected tropical diseases (NTD) as they are often ignored for their chronic disease outcome. However, they continue to be diseases of public health importance globally. Aim & Objectives: To analyze the epidemiology and distribution trend of STH infections from stool samples received in a tertiary care hospital in eastern India in the last decade. Material & Methods: A retrospective observational cross-sectional study was conducted based on stool examination findings from patients attending Calcutta School of Tropical Medicine which is a referral centre of excellence for HIV-AIDS between January 2012 and July 2022. These samples were subjected to direct microscopic examination following formol-ether concentration method, modified Ziehl-Neelsen and Trichrome staining techniques and were subsequently followed by culture by Harada-Mori technique.The data collected were subsequently analysed. Results: Out of 5821 stool samples, 736 (12.64%) revealed at least one STH and the most common STH detected was Trichuris trichiura (289 samples). The annual distribution revealed that 220 out of 811 (27.13%) samples obtained in 2012 had STH, while in 2021, 18 out of 1358 (1.33%) samples had STH, thereby reflecting a declining trend over the last decade. Conclusion: Trichuris trichiura was the most common STH infection in our study. There has been a sharp decline in STH infections in eastern India in the past decade, thereby reflecting successful therapeutic and preventive interventions. However, strict vigil through intensive laboratory diagnosis is needed to keep the prevalence of STH, a disease of public health importance, under control.

Introduction: Although the prevalence of intercarpal ligament injuries with distal radius fractures ranges from 0.5 to 75 percent, these injuries are often missed by the untrained eye. Currently, wrist arthroscopy is considered gold standard for diagnosis and treatment, but in Indian setting it is an impractical proposition. Scapho-lunate and luno-triquetral injuries can be identified on X rays easily by Gilula’s arc, scapholunate distance and angle, carpal height ratio etc. The aim of this study is to estimate the prevalence of intercarpal ligament injuries in distal radius (DER) fractures and determine their functional outcome at one year. Material and methods: The study was conducted over 18 months at VMMC and Safdarjung Hospital. Patients with distal radius fractures were subjected to wrist X rays in 100% magnification and earlier mentioned parameters were measured. Patients who needed surgery were operated for fracture DER. Immediate post-operative X rays and X rays at 1 year were compared with that of the contralateral wrist. Patients’ clinical outcomes like range of motion, grip strength, quick DASH score and pain on VAS were measured at one year to assess the clinical outcome. Results: The study population was of 103 patients. Prevalence of intercarpal injuries in patients with DER fractures was 11.7%. Out of these 12 patients, 50% had broken Gilula’s arc, 66.6% had increased scapho-lunate distance and 42% had increased scapho-lunate angle. Carpal height ratio was significantly less in patients with intercarpal ligament injuries at one year. Similarly, functional outcome was worse in these patients at one year. Conclusion: Intercarpal injuries are associated with worse outcomes in patients with fracture DER. These injuries can reliably diagnosed on X rays using the parameters mentioned. Since the prevalence is quite high, we should learn to diagnose them early, so that patients can be explained about the prognosis of their injury.

Human mobility contributes to the fast spatiotemporal propagation of infectious diseases. During an outbreak, monitoring the infection on either side of an international border is crucial as cross-border migration increases the risk of disease importation. Due to the unavailability of cross-border mobility data, mainly during pandemics, it becomes difficult to propose reliable, model-based strategies. In this study, we propose a method for estimating commuting-type cross-border mobility flux between any pair of regions that share an international border from the observed difference in their infection peak timings. Assuming the underlying disease dynamics are governed by a Susceptible–Infected–Recovered (SIR) model, we employ stochastic simulations to obtain the maximum likelihood cross-border mobility estimate for any pair of regions. We then investigate how the estimate of cross-border mobility flux varies depending on the transmission rate. We further show that the uncertainty in the estimates decreases for higher transmission rates and larger observed differences in peak timing. Finally, as a case study, we apply the method to some selected regions along the Poland–Germany border that are directly connected through multiple modes of transportation and quantify the cross-border fluxes from the COVID-19 cases data from 20 February to 20 June 2021.

Rhizopus oryzae is one of the major causative agents of mucormycosis. The disease has a poor prognosis with a high mortality rate, and resistance towards current antifungal drugs poses additional concern. The disease treatment is complicated with antifungals; therefore, surgical approach is preferred in many cases. A comprehensive understanding of the pathogenicity-associated virulence factors of R. oryzae is essential to develop new antifungals against this fungus. Virulence factors in R. oryzae include cell wall proteins, spore germination proteins and enzymes that evade host immunity. The spore coat protein (CotH3) and high-affinity iron permease (FTR1) have been identified as promising therapeutic targets in R. oryzae. In-silico screening is a preferred approach to identify hit molecules for further in-vitro studies. In the present study, twelve bioactive molecules were docked within the active site of CotH3 and FTR1. Further, molecular dynamics simulation analysis of best-docked protein-ligand structures revealed the dynamics information of their stability in the biological system. Eugenol and isoeugenol exhibited significant binding scores with both the protein targets of R. oryzae and followed the Lipinski rule of drug-likeness. To corroborate the in-silico results, in-vitro studies were conducted using bioactive compounds eugenol, isoeugenol, and myristicin against R. oryzae isolated from the soil sample. Eugenol, isoeugenol exhibited antifungal activity at 156 µg/mL whereas myristicin at 312 µg/mL. Hence, the study suggested that eugenol and isoeugenol could be explored further as potential antifungal molecules against R. oryzae.

BackgroundLong-term care facilities have been widely affected by the COVID-19 pandemic. Empirical evidence demonstrated that older people are the most impacted and are at higher risk of mortality after being infected. Regularly testing care facility residents is a practical approach to detecting infections proactively. In many cases, the care staff must perform the tests on the residents while also providing essential care, which in turn causes imbalances in their working time. Once an outbreak occurs, suppressing the spread of the virus in retirement homes (RHs) is challenging because the residents are in contact with each other, and isolation measures cannot be widely enforced. Regular testing strategies, on the other hand, have been shown to effectively prevent outbreaks in RHs. However, high-frequency testing may consume substantial staff working time, which results in a trade-off between the time invested in testing and the time spent providing essential care to residents. ObjectiveWe developed a web application (Retirement Home Testing Optimizer) to assist RH managers in identifying effective testing schedules for residents. The outcome of the app, called the “testing strategy,” is based on dividing facility residents into groups and then testing no more than 1 group per day. MethodsWe created the web application by incorporating influential factors such as the number of residents and staff, the average rate of contacts, the amount of time spent to test, and constraints on the test interval and size of groups. We developed mixed integer nonlinear programming models for balancing staff workload in long-term care facilities while minimizing the expected detection time of a probable infection inside the facility. Additionally, by leveraging symmetries in the problem, we proposed a fast and efficient local search method to find the optimal solution. ResultsConsidering the number of residents and staff and other practical constraints of the facilities, the proposed application computes the optimal trade-off testing strategy and suggests the corresponding grouping and testing schedule for residents. The current version of the application is deployed on the server of the Where2Test project and is accessible on their website. The application is open source, and all contents are offered in English and German. We provide comprehensive instructions and guidelines for easy use and understanding of the application’s functionalities. The application was launched in July 2022, and it is currently being tested in RHs in Saxony, Germany. ConclusionsRecommended testing strategies by our application are tailored to each RH and the goals set by the managers. We advise the users of the application that the proposed model and approach focus on the expected scenarios, that is, the expected risk of infection, and they do not guarantee the avoidance of worst-case scenarios.

During pandemics like COVID-19, both the quality and quantity of services offered by businesses and organizations have been severely impacted. They often have applied a hybrid home office setup to overcome this problem, although in some situations, working from home lowers employee productivity. So, increasing the rate of presence in the office is frequently desired from the manager's standpoint. On the other hand, as the virus spreads through interpersonal contact, the risk of infection increases when workplace occupancy rises. Motivated by this trade-off, in this paper, we model this problem as a bi-objective optimization problem and propose a practical approach to find the trade-off solutions. We present a new probabilistic framework to compute the expected number of infected employees for a setting of the influential parameters, such as the incidence level in the neighborhood of the company, transmission rate of the virus, number of employees, rate of vaccination, testing frequency, and rate of contacts among the employees. The results show a wide range of trade-offs between the expected number of infections and productivity, for example, from 1 to 6 weekly infections in 100 employees and a productivity level of 65% to 85%. This depends on the configuration of influential parameters and the occupancy level. We implement the model and the algorithm and perform several experiments with different settings of the parameters. Moreover, we developed an online application based on the result in this paper which can be used as a recommender for the optimal rate of occupancy in companies/workplaces.

Curvuluria lunata is a melanized fungus pathogenic to both plants and animals including humans, causing from mild, febrile to life-threatening illness if not well treated. In humans, it is an etiological agent of keratomycosis, sinusitis, and onychomycosis in immunocompromised and immunocompetent patients. The development of multiple-drug-resistant strains poses a critical treatment issue as well as public health problem. Natural products are attractive prototypes for drug discovery due to their broad-spectrum efficacy and lower side effects. The present study explores possible targets of natural antifungal compounds (α-pinene, eugenol, berberine, and curcumin) against C. lunata via gene expression analysis, molecular docking interaction, and molecular dynamics (MD) studies. Curcumin, berberine, eugenol, and α-pinene exhibited in vitro antifungal activity at 78 μg/ml, 156 μg/ml, 156 μg/ml, and 1250 μg/ml, respectively. In addition, treatment by these compounds led to the complete inhibition of conidial germination and hindered the adherence when observed on onion epidermis. Several pathogenic factors of fungi are crucial for their survival inside the host including those involved in melanin biosynthesis, hyphal growth, sporulation, and mitogen-activated protein kinase (MAPK) signalling. Relative gene expression of velB, brn1, clm1, and pks18 responsible for conidiation, melanin, and cell wall integrity was down-regulated significantly. Results of molecular docking possessed good binding affinity of compounds and have confirmed their potential targets as THR and VelB proteins. The docked structures, having good binding affinity among all, were further refined, and rescored from their docked poses through 100-ns long MD simulations. The MDS study revealed that curcumin formed a stable and energetically stabilized complex with the target protein. Therefore, the study concludes that the antifungal compounds possess significant efficacy to inhibit C. lunata growth targeting virulence proteins/genes involved in spore formation and melanin biosynthesis.

Retroperitoneal nonfunctional extraadrenal paragangliomas are uncommon neoplasms arising from the aorticosympathetic chain of paraganglia. Biopsy of these tumors shows diverse cytomorphological features which can pose a significant diagnostic challenge to the histopathologist. We report a case of a 36-year-old male presenting with abdominal pain and a retroperitoneal mass anterior to the left kidney observed on ultrasound and computed tomography (CT) scan. CT-guided needle core biopsy was carried out which revealed varied cytological features suggesting a wide spectrum of differential diagnosis. Knowledge of the histological features along with immunohistochemistry helped us to diagnose this case. Since surgical excision is the preferred treatment of choice, early and accurate diagnosis is of utmost importance.

Early flowering, maturity, and plant height are important traits for linseed to fit in rice fallows, for rainfed agriculture, and for economically viable cultivation. Here, Multi-Locus Genome-Wide Association Study (ML-GWAS) was undertaken in an association mapping panel of 131 accessions, genotyped using 68,925 SNPs identified by genotyping by sequencing approach. Phenotypic evaluation data of five environments comprising 3 years and two locations were used. GWAS was performed for three flowering time traits including days to 5%, 50%, and 95% flowering, days to maturity, and plant height by employing five ML-GWAS methods: FASTmrEMMA, FASTmrMLM, ISIS EM-BLASSO, mrMLM, and pLARmEB. A total of 335 unique QTNs have been identified for five traits across five environments. 109 QTNs were stable as observed in ≥2 methods and/or environments, explaining up to 36.6% phenotypic variance. For three flowering time traits, days to maturity, and plant height, 53, 30, and 27 stable QTNs, respectively, were identified. Candidate genes having roles in flower, pollen, embryo, seed and fruit development, and xylem/phloem histogenesis have been identified. Gene expression of candidate genes for flowering and plant height were studied using transcriptome of an early maturing variety Sharda (IC0523807). The present study unravels QTNs/candidate genes underlying complex flowering, days to maturity, and plant height traits in linseed.

S1PR3 is a G protein coupled receptor, that has a role in inflammation. Here the authors show that in the CNS, S1PR3 may contribute to resilience to stressful experiences; resilient rodents show elevated S1pr3, and knockdown results in greater susceptibility to stress.

Vitiligo is a disease of mysterious origins in the context of its occurrence and pathogenesis. The autoinflammatory theory is perhaps the most widely accepted theory that discusses the occurrence of Vitiligo. The theory elaborates the clinical association of vitiligo with autoimmune disorders such as Psoriasis, Multiple Sclerosis and Rheumatoid Arthritis and Diabetes. In the present work, we discuss the comprehensive set of differentially co-expressed genes involved in the crosstalk events between Vitiligo and associated autoimmune disorders (Psoriasis, Multiple Sclerosis and Rheumatoid Arthritis). We progress our previous tool, Vitiligo Information Resource (VIRdb), and incorporate into it a compendium of Vitiligo-related multi-omics datasets and present it as VIRdb 2.0. It is available as a web-resource consisting of statistically sound and manually curated information. VIRdb 2.0 is an integrative database as its datasets are connected to KEGG, STRING, GeneCards, SwissProt, NPASS. Through the present study, we communicate the major updates and expansions in the VIRdb and deliver the new version as VIRdb 2.0. VIRdb 2.0 offers the maximum user interactivity along with ease of navigation. We envision that VIRdb 2.0 will be pertinent for the researchers and clinicians engaged in drug development for vitiligo.

In many cases of inherited retinal degenerations, ganglion cells are spared despite photoreceptor cell death, making it possible to stimulate them to restore visual function. Several studies have shown that it is possible to express an optogenetic protein in ganglion cells and make them light sensitive, a promising strategy to restore vision. However the spatial resolution of optogenetically-reactivated retinas has rarely been measured, especially in the primate. Since the optogenetic protein is also expressed in axons, it is unclear if these neurons will only be sensitive to the stimulation of a small region covering their somas and dendrites, or if they will also respond to any stimulation overlapping with their axon, dramatically impairing spatial resolution. Here we recorded responses of mouse and macaque retinas to random checkerboard patterns following an in vivo optogenetic therapy. We show that optogenetically activated ganglion cells are each sensitive to a small region of visual space. A simple model based on this small receptive field predicted accurately their responses to complex stimuli. From this model, we simulated how the entire population of light sensitive ganglion cells would respond to letters of different sizes. We then estimated the maximal acuity expected by a patient, assuming it could make an optimal use of the information delivered by this reactivated retina. The obtained acuity is above the limit of legal blindness. Our model also makes interesting predictions on how acuity might vary upon changing the therapeutic strategy, assuming an optimal use of the information present in the retinal activity. Optogenetic therapy could thus potentially lead to high resolution vision, under conditions that our model helps to determinine.

Vitiligo is a chronic asymptomatic disorder affecting melanocytes from the basal layer of the epidermis which leads to a patchy loss of skin color. Even though it is one of the neglected disease conditions, people suffering from vitiligo are more prone to psychological disorders. As of now, various studies have been done in order to project auto-immune implications as the root cause. To understand the complexity of vitiligo, we propose the Vitiligo Information Resource (VIRdb) that integrates both the drug-target and systems approach to produce a comprehensive repository entirely devoted to vitiligo, along with curated information at both protein level and gene level along with potential therapeutics leads. These 25,041 natural compounds are curated from Natural Product Activity and Species Source Database. VIRdb is an attempt to accelerate the drug discovery process and laboratory trials for vitiligo through the computationally derived potential drugs. It is an exhaustive resource consisting of 129 differentially expressed genes, which are validated through gene ontology and pathway enrichment analysis. We also report 22 genes through enrichment analysis which are involved in the regulation of epithelial cell differentiation. At the protein level, 40 curated protein target molecules along with their natural hits that are derived through virtual screening. We also demonstrate the utility of the VIRdb by exploring the Protein–Protein Interaction Network and Gene–Gene Interaction Network of the target proteins and differentially expressed genes. For maintaining the quality and standard of the data in the VIRdb, the gold standard in bioinformatics toolkits like Cytoscape, Schrödinger’s GLIDE, along with the server installation of MATLAB, are used for generating results. VIRdb can be accessed through “http://www.vitiligoinfores.com/”.

Abstract Targeting the photosensitive ion channel channelrhodopsin‐2 (ChR2) to the retinal circuitry downstream of photoreceptors holds promise in treating vision loss caused by retinal degeneration. However, the high intensity of blue light necessary to activate channelrhodopsin‐2 exceeds the safety threshold of retinal illumination because of its strong potential to induce photochemical damage. In contrast, the damage potential of red‐shifted light is vastly lower than that of blue light. Here, we show that a red‐shifted channelrhodopsin (ReaChR), delivered by AAV injections in blind rd1 mice, enables restoration of light responses at the retinal, cortical, and behavioral levels, using orange light at intensities below the safety threshold for the human retina. We further show that postmortem macaque retinae infected with AAV‐ReaChR can respond with spike trains to orange light at safe intensities. Finally, to directly address the question of translatability to human subjects, we demonstrate for the first time, AAV‐ and lentivirus‐mediated optogenetic spike responses in ganglion cells of the postmortem human retina.

HEPNet is an electronic representation of metabolic reactions occurring within human cellular organization focusing on inflow and outflow of the energy currency ATP, GTP and other energy associated moieties. The backbone of HEPNet consists of primary bio-molecules such as carbohydrates, proteins and fats which ultimately constitute the chief source for the synthesis and obliteration of energy currencies in a cell. A series of biochemical pathways and reactions constituting the catabolism and anabolism of various metabolites are portrayed through cellular compartmentalization. The depicted pathways function synchronously toward an overarching goal of producing ATP and other energy associated moieties to bring into play a variety of cellular functions. HEPNet is manually curated with raw data from experiments and is also connected to KEGG and Reactome databases. This model has been validated by simulating it with physiological states like fasting, starvation, exercise and disease conditions like glycaemia, uremia and dihydrolipoamide dehydrogenase deficiency (DLDD). The results clearly indicate that ATP is the master regulator under different metabolic conditions and physiological states. The results also highlight that energy currencies play a minor role. However, the moiety creatine phosphate has a unique character, since it is a ready-made source of phosphoryl groups for the rapid synthesis of ATP from ADP. HEPNet provides a framework for further expanding the network diverse age groups of both the sexes, followed by the understanding of energetics in more complex metabolic pathways that are related to human disorders.