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Context: Alpha-glucosidase enzyme is considered an important therapeutic target for controlling hyperglycemia associated with type 2 diabetes. Novel scaffolds identified as potential alpha-glucosidase inhibitors from the Maybridge library utilizing pharmacophore modeling, molecular docking and biological evaluation are reported in this manuscript., Method: A total of 51 xanthone series scaffolds previously reported as alpha-glucosidase inhibitors were collected and used as training and test sets. These sets were employed to develop and validate a pharmacophore-based 3D-QSAR model with statistically meaningful results using Schrodinger software. The model showed a high F value (F, 80.1) at five component partial least square factors, a high cross-validation coefficient (Q 2 , 0.66) and a good correlation coefficient (R 2 , 0.95). Pearson correlation coefficient (r) of 0.8400 indicated a greater degree of confidence in the model. Subsequently, virtual screening was performed with PHASE module of Schrodinger software using the above model to identify novel alpha-glucosidase inhibitors, and mapped compounds were evaluated for their interactions with the protein. The X-ray co-crystallised structure of the alpha-glucosidase protein in complex with acarbose (PDB Code: 5NN8) was used for molecular docking analysis using GLIDE module and a total of eight compounds were further selected for biological evaluation. Molecular dynamics analysis using GROMACS software was performed in the active site of alpha-glucosidase protein to gain insights into binding mechanism of the four active compounds which were finally found to exhibit inhibitory activity in the biological assay., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Several non-invasive technologies are nowadays available in the market which claim to determine the hemoglobin levels instantly without the requirement of the blood sample. But no study has shown the significance of such non-invasive devices on a routine basis for determining their impact on anemia reduction programs. This study is conducted to determine the impact of regular hemoglobin screening on the women population to determine its potential in reducing anemia, using a digitalized non-invasive device., Method: A cross-sectional study was conducted on 203 women of reproductive age group, residing in the Moradabad district. Repetitive readings were taken after a time interval of a minimum of 1 month for determining the impact of regular screening. The entire data collection process was carried out using the EzeCheck mobile app., Results: It was observed that the prevalence of anemia was reduced upon the second time screening and was accepted by the women population. Repetitive testing has a significant impact on reducing anemia prevalence. Also, the simplified non-invasive technology for estimating the hemoglobin values, makes the user more comfortable to take the test., Conclusion: Non-invasive devices should be used regularly to keep track of hemoglobin levels which will help in the effective treatment of anemia. The mobile app-based testing could help to easily evaluate the reports of the patients from any remote location with instant result interpretation and health assistance.

Introduction: Postpartum period is a critical period for a woman, where the body of the woman is in healing stage. In this situation, there arises the risk for developing anemia, if proper diet is not maintained. So, it is necessary to routinely determine the hemoglobin levels during this period to avoid chances of developing anemia and assist in early diagnosis., Methodology: A cross-sectional study was carried out at the maternity ward of Kalinga Institute of Medical Sciences Hospital, Bhubaneswar. The study was conducted for a period of 5-6 months by received approval from the concerned institutional committee. The study involved women participants having age above 18 years and who had recently undergone delivery. Written informed consent was taken from all the participants prior to their enrolment for this study., Results: A total of 670 women were involved in this study and more than 50% of the women were found to be affected by anemia. A Pearson's correlation of 0.87 was observed with sensitivity of 95.69% and specificity of 67.06% between the hematology analyzer and non-invasive EzeCheck device in determining anemia., Conclusion: Women often neglect their health situations and always prioritize their family's wellbeing and health over their own. This avoidance results in the development of a chronic disease which in the long run becomes difficult to be cured. So, in such situations, it is necessary to inculcate certain routine tests for the women during their healing period (such as postpartum stage) to keep an eye on their health status. Use of non-invasive devices can help in achieving this in a painless and much effective manner with instant reporting of the results., (© The Author(s) 2024. Published by Mary Ann Liebert, Inc.)

Rheumatoid Arthritis (RA) is a well-known autoimmune inflammatory disease, distressing roughly 1% of the adult population throughout the globe. Many studies have suggested that overexpression of TNF-α, a pro-inflammatory cytokine, is responsible for the progression of RA. Furthermore, inhibition of the shedding rate of TNF-α is regulated by the TACE (TNF-α converting enzyme) protein and, hence is considered as an important therapeutic target for the prevention of progressive synovial joint destruction in rheumatoid arthritis. In the present study, we have proposed a deep neural network (DNN)-based workflow for the virtual screening of compounds towards the identification of potential inhibitors against the TACE proteins. Subsequently, a set of compounds were shortlisted, based on the molecular docking and subjected to the biological evaluation to validate the inhibitory activities of the screened compounds, determine the practical applicability of the DNN-based model, and strengthen the hypothesis. Out of seven, three compounds (BTB10246, BTB10247, and BTB10245) showed significant inhibition at 10 µM and 0.1 µM concentration. These three compounds also showed a stable and significant interaction potential against the TACE protein as compared with the re-docked complex system and can serve as a novel scaffold for further design of new molecules with improved inhibitory activities against TACE.Communicated by Ramaswamy H. Sarma.

Anaemia is a major public health problem, especially in resource constrained settings. Dependency on assessment of blood hemoglobin (Hgb) concentration impedes anemia detection, risk stratification and intervention. Thus, valid, frugal and scalable technologies are needed. EzeCheck is a noninvasive portable device developed in India for predicting hemoglobin levels in human beings aged 4 years and above using a finger-tip biosensor. In this assessment, we aimed to: (i) evaluate EzeCheck's performance with an automated whole blood hemato-analyzer (Sysmex XN 1000) as the gold standard, and (ii) estimate EzeCheck's agreement with Sahli's method and HemoCue (Hb-301) in real-world primary and higher care facilities. Paired assessments were done at five sites across India i.e., Bhubaneshwar, Shimla, Solan and Mashobra and Ulhasnagar. Participants across all age groups (4 years and above) were assessed. We used a range of statistical tests to evaluate the performance of EzeCheck. It was found that EzeCheck performed well across age and gender categories with convincing validity, concordance, precision and accuracy, and acceptable bias. While comparing EzeCheck with Hemato-analyzer, no statistically significant systematic bias was found. However, EzeCheck showed significant systematic bias when compared to Sahli's method and HemoCue. We concluded that EzeCheck could detect anemia (as per WHO Hgb cut-offs) in 'real-world settings' and 'across age and gender categories', with high sensitivity, specificity and accuracy, and can serve as a replacement to traditional methods of hemoglobin assessment. Further, for countries with higher prevalence of anemia where universal screening may be mandated, the positive predictive value of EzeCheck will be higher. The likelihood ratios also indicated that the device had moderate-to-good utility. EzeCheck is suitable for embedment into program and out-patient health care settings in resource constrained contexts as a spot-check hemoglobinometer., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Das Mahapatra et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Cathepsin K is a type of cysteine proteinase that is primarily expressed in osteoclasts and has a key role in the breakdown of bone matrix protein during bone resorption. Many studies suggest that the deficiency of cathepsin K is concomitant with a suppression of osteoclast functioning, therefore rendering the resorptive properties of cathepsin K the most prominent target for osteoporosis. This innovative work has identified a novel anti-osteoporotic agent against Cathepsin K by using a comparison of machine learning and deep learning-based virtual screening followed by their biological evaluation. Out of ten shortlisted compounds, five of the compounds (JFD02945, JFD02944, RJC01981, KM08968 and SB01934) exhibit more than 50% inhibition of the Cathepsin K activity at 0.1 μM concentration and are considered to have a promising inhibitory effect against Cathepsin K. The comprehensive docking, MD simulation, and MM/PBSA investigations affirm the stable and effective interaction of these compounds with Cathepsin K to inhibit its function. Furthermore, the compounds RJC01981, KM08968 and SB01934 are represented to have promising anti-osteoporotic properties for the management of osteoporosis owing to their significantly well predicted ADMET properties., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Salt stress is a recognized annihilating abiotic stress that has a significant impact on agricultural and horticulture crop productivity. Plant development faces three distinct dangers as a result of salt stress: oxidative stress, osmotic stress, and ionic toxicity. It has been shown that plants can forecast diurnal patterns using the circadian clock; moreover, they can manage their defensive mechanism for the detoxification of reactive oxygen species (ROS). Circadian rhythmicity in gene expression assembles transcription and translation feedback networks to govern plant shape, physiology, cellular and molecular activities. Both external and internal variables influence the systemic rhythm via input routes. The Malav Jyoti (MJ) and Delhi Green (DG) genotypes of spinach (Spinacia oleracea) were grown in the plant growth chamber. The chamber had an optimized temperature of 25 °C and humidity of 65% containing light emitting diode (LED) having Red: Blue: white (one side) and White fluorescent (other side) under salinity stress. The samples were collected on the basis of 4 h intervals of circadian hours (0 h, 4 h, 8 h and 12 h) during Day-10 and Day-20 of salt treatments. Under salt stress, the circadian and light-emitting diode-based strategy had a substantial influence on spinach's anti-oxidative responses, stomatal movement, CO 2 assimilation, PS-I and II efficiency, phytochrome pigment efficiency, and photosynthesis. Based on the findings of the free radical scavenging enzyme tests, the photoperiodic hours for the proteome analysis were set to 11 am and 3 pm on Day-20. When compared to white fluorescent, this study found that LED has the capacity to influence the entrainment cues of the circadian clock in the cultivation of salt-sensitive spinach genotypes. According to our findings, changing the cellular scavenging mechanism and chloroplast proteome has increased the survival rate of spinach genotypes under LED when compared to white fluorescent., Competing Interests: Declaration of competing interest Authors declare no conflict of interest., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Aldose reductase (ALR2) is a notable enzyme of the polyol pathway responsible for aggravating diabetic neuropathy complications. The first step begins when it catalyzes the reduction of glucose to sorbitol with NADPH as a coenzyme. Elevated concentrations of sorbitol damage the tissues, leading to complications like neuropathy. Though considerable effort has been pushed toward the successful discovery of potent inhibitors, its discovery still remains an elusive task. To this end, we present a 3D convolutional neural network (3D-CNN) based ALR2 inhibitor classification technique by dealing with snapshots of images captured from 3D chemical structures with multiple rotations as input data. The CNN-based architecture was trained on the 360 sets of image data along each axis and further prediction on the Maybridge library by each of the models. Subjecting the retrieved hits to molecular docking leads to the identification of the top 10 molecules with high binding affinity. The hits displayed a better blood-brain barrier penetration (BBB) score (90% with more than four scores) as compared to standard inhibitors (38%), reflecting the superior BBB penetrating efficiency of the hits. Followed by molecular docking, the biological evaluation spotlighted five compounds as promising ALR2 inhibitors and can be considered as a likely prospect for further structural optimization with medicinal chemistry efforts to improve their inhibition efficacy and consolidate them as new ALR2 antagonists in the future. In addition, the study also demonstrated the usefulness of scaffold analysis of the molecules as a method for investigating the significance of structurally diverse compounds in data-driven studies. For reproducibility and accessibility purposes, all of the source codes used in our study are publicly available.

Navneet Kaur Background  Fatigue is one of the commonest sequelae of breast cancer treatment that adversely impacts quality of life (QOL) of breast cancer survivors (BCSs). However, very limited data are available about cancer-related fatigue in Indian patients. Hence, this study was planned with the objectives to study (1) prevalence of fatigue in short-, intermediate-, and long-term follow-up; (2) severity and characteristics of fatigue; (3) impact of fatigue on QOL; and (4) correlation of fatigue with other survivorship issues. Materials and Methods  The study was conducted on ( n  = 230) BCSs who had completed their primary treatment (surgery, radiotherapy, and chemotherapy) and were coming for follow-up. The prevalence of fatigue was noted from a screening tool, which comprised of 14 commonly reported survivorship issues. Assessment of fatigue was done by using survivorship fatigue assessment tool-1 score and QOL was assessed by functional assessment of cancer therapy-breast (FACT-B) questionnaires. To understand how fatigue evolved over time, survivors were divided into three groups according to the time elapsed since initial treatment: Group 1: <2 years ( n  = 105); Group 2: 2-5 years ( n  = 70); Group 3: >5 years ( n  = 55). Statistical Analysis  Data was analyzed by using simple descriptive statistics, one way analysis of variance followed by Tukey's test for comparison of quantitative data among the three groups, and Pearson correlation coefficients for association of fatigue with other survivorship issues. Results  Clinically significant fatigue (≥4) was noted in 38% of BCSs. However, high overall prevalence of fatigue (60%) was seen, which persisted in long-term survivors (51%) as well. Severity of fatigue was mostly mild (37.7%) to moderate (47.1%). Fatigue scores were significantly higher in short-term survivors ( 5.01 ± 2.06) than intermediate- (4.03 ± 1.42) and long-term BCSs (3.57 ± 1.37). The mean score on FACT-B was 90.07 ± 10.17 in survivors with fatigue and 104.73 ± 7.13 in those without fatigue ( p  = 0.000). Significant correlation of fatigue was seen with other survivorship issues like limb swelling, chronic pain, premature menopause, and its related symptoms and emotional distress. Conclusion  Fatigue is highly prevalent in BCSs. Survivorship care programs should include appropriate measures to evaluate and address fatigue., Competing Interests: Conflict of Interest None declared., (MedIntel Services Pvt Ltd. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Background: Defects in DNA repair pathway can lead to double-strand breaks leading to genomic instability. Earlier we have shown that S.pombe Drp1, a Rint1/Tip1 family protein is required for the recovery from DNA damage., Methods: Various truncations of Drp1 protein were constructed and their role in DNA damage response and interaction with Rad50 protein has been studied by co-immunoprecipitation and pull-down assays., Results: The structural and functional analysis of Drp1 protein revealed that the N-terminus region of Drp1 is indispensable for the survival. The C-terminus truncation mutants, drp1C1Δ and drp1C2Δ exhibit temperature sensitive phenotype and are hypersensitive against DNA damaging agents with elevated level of Rad52-YFP foci at non-permissive temperature indicating the impairment for DNA damage repair pathway. The essential N-terminus region of Drp1 interacts with the C-terminus region of Rad50 and might be involved in influencing the MRN/X function. Small-angle X-ray (SAXS) analysis revealed three-domain like shapes in Drp1 protein while the C-terminus region of Rad50 exhibit unusual bulges. Computational docking studies revealed the amino acid residues at the C-terminus region of Rad50 that are involved in the interaction with the residues present at the N-terminal region of Drp1 indicating the importance of the N-terminal region of Drp1 protein., Conclusions: We have identified the region of Drp1 and Rad50 proteins that are involved in the interaction and their role in the DNA damage response pathway has been analyzed., General Significance: The functional and structural aspects of fission yeast Drp1 protein and its interaction with Rad50 have been elucidated., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Molecular interaction of aromatic dyes with biological macromolecules are important for the development of minimally invasive disease diagnostic biotechnologies. In the present work, we have used Toluidine Blue (TB) as a model dye, which is a well-known staining agent for the diagnosis of oral cancer and have studied the interaction of various biological macromolecules (protein and DNA) with the dye at different pH. Our spectroscopic studies confirm that TB interacts with Human Serum Albumin (HSA), a model protein at very high pH conditions which is very hard to achieve physiologically. On the other hand, TB significantly interacts with the DNA at physiological pH value (7.4). Our molecular studies strengthen the understanding of the Toluidine Blue staining of cancer cells, where the relative ratio of the nucleic acids is higher than the normal intracellular content. We have also developed a non-invasive, non-contact spectroscopic technique to explore the possibility of quantitatively detecting oral cancer by exploiting the interaction of TB with DNA. We have also reported development of a prototype named "Oral-O-Scope" for the detection of Oral cancer and have carried out human studies using the prototype., (Copyright © 2020 Singh, Halder, Sinha, Chakrabarty, Chatterjee, Adhikari, Singh, Shikha, Ghosh, Banerjee, Das Mahapatra, Mandhar, Bhattacharyya, Bose, Ahmed, Alharbi, Hameed and Pal.)

Ultraviolet radiation, an effective sterilizing source, rapidly kills the causative organism (Mycobacterium leprae) of leprosy. But, the reasons behind this quick death are not clearly understood. Also, the impact of UV radiation on the antigen(s) which is/are responsible for the survival of this pathogen is still unknown. Many reports have revealed that M. leprae secrets a major immunodominant antigen, namely HSP18, whose chaperone function plays an important role in the growth and survival of this pathogen under various environmental insults. However, the effect of UV radiation on its structure and chaperone function is still unclear. Therefore, we have taken a thorough attempt to understand these two aspects of HSP18 under different UV radiations (UVA/UVB/UVC; doses: 1-50 J/cm 2 ). Our study revealed that its chaperone function is decreased significantly with increasing doses of various UV radiations. These different UV irradiations perturb only its tertiary structure and induce tryptophan and tyrosine photo-oxidation to N-formyl kynurenine, kynurenine and dityrosine. Such photo-oxidation promotes the subunit cross-linking within a HSP18 oligomer, lowers the surface hydrophobicity and thermostability of the protein. All these factors together damage/reduce the chaperone function of HSP18 which may be an important factor behind the rapid death of M. leprae under UV exposure., (Copyright © 2018 Elsevier B.V. All rights reserved.)