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Engineering design optimization poses a significant challenge, usually requiring human expertise to discover superior solutions. Although various search techniques have been employed to generate diverse designs, their effectiveness is often limited by problem-specific parameter tuning, making them less generalizable and scalable. This article introduces a framework inspired by evolutionary and developmental (evo-devo) concepts, aiming to automate the evolution of structural engineering designs. In biological systems, evo-devo governs the growth of single-cell organisms into multicellular organisms through the use of gene regulatory networks (GRNs). GRNs are inherently complex and highly nonlinear, and this article explores the use of neural networks and genetic programming as artificial representations of GRNs to emulate such behaviors. To evolve a wide range of Pareto fronts for artificial GRNs, this article introduces a new technique, a real value-encoded neuroevolutionary method termed real-encoded NEAT (RNEAT). The performance of RNEAT is compared with that of two well-known evolutionary search techniques across different 2-D and 3-D problems. The experimental results demonstrate two key findings. First, the proposed framework effectively generates a population of GRNs that can produce diverse structures for both 2-D and 3-D problems. Second, the proposed RNEAT algorithm outperforms its competitors on more than 50% of the problems examined. These results validate the proof of concept underlying the proposed evo-devo-based engineering design evolution., (© 2024 Massachusetts Institute of Technology.)

Cyclin-dependent kinases (CDKs) constitute a vital family of protein-serine kinases, pivotal in regulating various cellular processes such as the cell cycle, metabolism, proteolysis, and neural functions. Dysregulation or overexpression of CDK kinases is directly linked to the development of cancer. However, the currently approved CDK inhibitors by the US FDA, such as palbociclib, ribociclib, Trilaciclib, Abemaciclib, etc., although effective, exhibit limited specificity and often lead to undesirable adverse effects. First and second-generation CDK inhibitors have not gained significant clinical interaction due to their high toxicity and lack of specificity. To address these challenges, a combined approach is being employed in the quest for newer CDK inhibitors aimed at mitigating toxicity and side effects associated with CDKIs. The discovery of therapeutic agents selectively targeting tumorous cells, such as CDK inhibitors, has demonstrated promise in treating various cancers, including breast cancer. Extensive literature reviews have facilitated the development of novel CDK inhibitors by combining medicinally preferred pyrimidine derivatives with other heterocyclic rings. Pyrimidine derivatives substituted with pyrazole, imidazole, benzamide, benzene sulfonamide, indole carbohydrazide, and other privileged heterocyclic rings have shown encouraging efficacy in inhibiting cyclin-dependent kinase activity. This review provides comprehensive data, including structure-activity relationship (SAR), anticancer activity, and kinetics studies of potent compounds. Additionally, molecular docking studies with compounds under clinical trial and patents filed on pyrimidine based CDK inhibitors in cancer treatment are included. This review serves as a valuable resource for further development of CDK kinase inhibitors for cancer treatment, offering insights into their efficacy, specificity, and potential clinical applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: PIM Kinases (PIM-1, PIM-2, and PIM-3) have been reported to play crucial role in signaling cascades that govern cell survival, proliferation, and differentiation. Over-expression of these kinases leads to hematological malignancies such as diffuse large B cell lymphomas (DLBCL), multiple myeloma, leukemia, lymphoma and prostate cancer etc. PIM kinases as biomarkers and potential therapeutic targets have shown promise toward precision cancer therapy. The selective PIM-1, PIM-2, and/or PIM-3 isoform inhibitors have shown significant results in patients with advanced stages of cancer including relapsed/refractory cancer., Areas Covered: A comprehensive literature review of PIM Kinases (PIM-1, PIM-2, and PIM-3) in oncogenesis, the patented PIM kinase inhibitors (2016-Present), and their pharmacological and structural insights have been highlighted., Expert Opinion: Recently, PIM kinases viz. PIM-1, PIM-2, and PIM-3 (members of the serine/threonine protein kinase family) as therapeutic targets have attracted considerable interest in oncology especially in hematological malignancies. The patented PIM kinase inhibitors comprised of heterocyclic (fused)ring structure(s) like indole, pyridine, pyrazine, pyrazole, pyridazine, piperazine, thiazole, oxadiazole, quinoline, triazolo-pyridine, pyrazolo-pyridine, imidazo-pyridazine, oxadiazole-thione, pyrazolo-pyrimidine, triazolo-pyridazine, imidazo-pyridazine, pyrazolo-quinazoline and pyrazolo-pyridine etc. showed promising results in cancer chemotherapy.

One of the most perilous illnesses in the world is cancer. The cancer may be associated with the mutation of different genes inside the body. The PIM kinase, also known as the serine/threonine kinase, plays a critical role in the biology of different kinds of cancer. They are widely distributed and associated with several biological processes, including cell division, proliferation, and death. Aberration of PIM-1 kinase is found in varieties of cancer. Prostate cancer and leukemia can both be effectively treated with PIM-1 kinase inhibitors. There are several potent compounds that have been explored in this review based on heterocyclic compounds for the treatment of prostate cancer and leukemia that have strong effects on the suppression of PIM-1 kinase. The present review summarizes the PIM-1 kinase pathway, their inhibitors under clinical trial, related patents, and SAR studies of several monocyclic, bicyclic, and polycyclic compounds. The study related to their molecular interactions with receptors is also included in the present manuscript. The study may be beneficial to scientists for the development of novel compounds as PIM-1 inhibitors in the treatment of prostate cancer and leukemia., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The conventional one-drug-one-disease theory has lost its sheen in multigenic diseases such as Alzheimer's disease (AD). Propolis, a honeybee-derived product has ethnopharmacological evidence of antioxidant, anti-inflammatory, antimicrobial and neuroprotective properties. However, the chemical composition is complex and highly variable geographically. So, to leverage the potential of propolis as an effective treatment modality, it is essential to understand the role of each phytochemical in the AD pathophysiology. Therefore, the present study was aimed at investigating the anti-Alzheimer effect of bioactive in Indian propolis (IP) by combining LC-MS/MS fingerprinting, with network-based analysis and experimental validation. First, phytoconstituents in IP extract were identified using an in-house LC-MS/MS method. The drug likeness and toxicity were assessed, followed by identification of AD targets. The constituent-target-gene network was then constructed along with protein-protein interactions, gene pathway, ontology, and enrichment analysis. LC-MS/MS analysis identified 16 known metabolites with druggable properties except for luteolin-5-methyl ether. The network pharmacology-based analysis revealed that the hit propolis constituents were majorly flavonoids, whereas the main AD-associated targets were MAOB, ESR1, BACE1, AChE, CDK5, GSK3β, and PTGS2. A total of 18 gene pathways were identified to be associated, with the pathways related to AD among the topmost enriched. Molecular docking analysis against top AD targets resulted in suitable binding interactions at the active site of target proteins. Further, the protective role of IP in AD was confirmed with cell-line studies on PC-12, in situ AChE inhibition, and antioxidant assays., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Cancer stands as one of the deadliest diseases, ranking second in terms of its global impact. Despite the presence of numerous compelling theories concerning its origins, none have succeeded in fully elucidating the intricate nature of this ailment. Among the prevailing concerns in today's world, breast cancer proliferation remains a significant issue, particularly affecting females. The abnormal proliferation of the PI3K pathway emerges as a prominent driver of breast cancer, underscoring its role in cellular survival and proliferation. Consequently, targeting this pathway has emerged as a leading strategy in breast cancer therapeutics. Within this context, the present article explores the current landscape of anti-tumour drug development, focusing on structural activity relationships (SAR) in PI3K targeting breast cancer treatment. Notably, certain moieties like triazines, pyrimidine, quinazoline, quinoline, and pyridoxine have been explored as potential PI3K inhibitors for combating breast cancer. Various heterocyclic small molecules are undergoing clinical trials, such as Alpelisib, the first orally available FDA-approved drug targeting PI3K; others include buparlisib, pictilisib, and taselisib, which inhibit class I PI3K. These drugs are used for the treatment of breast cancer but still have various side effects with their high cost. Therefore, the primary goal of this review is to include all current advances in the development of anticancer medicines that target PI3K over-activation in the treatment of breast cancer., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr Vivek Asati reports was provided by ISF College of Pharmacy. Dr Vivek Asati reports a relationship with ISF College of Pharmacy that includes: employment. Dr Vivek Asati has patent Novel indole clubbed triazole derivatives as α-glucosidase inhibitors, their synthesis and uses thereof pending to Assignee. No., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Non-small cell Lung cancer (NSCLC) is the most common type of lung cancer, which is caused by high consumption of tobacco and smoking. It is an epithelial lung cancer that affects about 2.2 million people across the globe, according to International Agency for Research on Cancer (IARC). Non-small cell lung cancer is a malignant tumor caused by EGFR mutation that occurs in the in-frame deletion of exon 19 and L858R point mutation in exon 21. Presently, clinically available inhibitors of EGFR (including erlotinib, lapatinib, gefitinib, selumetinib, etc.) are not specific and responsible for undesirable adverse effects. Moreover, to solve this problem search for newer EGFR inhibitors is the utmost need for the treatment and/or management of increasing lung cancer burden. The discovery of therapeutic agents that inhibit the specific target in tumorous cells, such as EGFR, is one of the successful strategies in treating many cancer therapies, including lung cancer. The exhaustive literature survey (2018-2023) has shown the importance of medicinally privileged pyrimidine derivatives together, fused and/or clubbed with other heterocyclic rings to design and develop novel EGFR inhibitors. Pyrimidine derivatives substituted with phenylamine, indole, pyrrole, piperazine, pyrazole, thiophene, pyridine and quinazoline derivatives substituted with phenylamine, pyrimidine, morpholine, pyrrole, dioxane, acrylamide, indole, pyridine, furan, pyrimidine, pyrazole etc. are privileged heterocyclic rings shown promising activity by inhibiting EGFR and TKIs. The present review summarizes the structure-activity relationship (SAR) and enzyme inhibitory activity, including IC 50 values, percentage inhibition, and kinetic studies of potential compounds from various literature. The review also includes various aspects of molecular docking studies with compounds under clinical trials and patents filed on pyrimidine-based EGFR inhibitors in treating non-small cell lung cancer. The present review may benefit the medicinal chemist for developing novel compounds such as EGFR inhibitors., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Royal jelly is an anti-inflammatory, antioxidant, and neuroprotective bee product. There are several sources for royal jelly and one of them is Indian Royal Jelly (IRJ). However, the neuroprotective actions of IRJ and the underlying molecular mechanisms involved are not well known., Objective: To evaluate the neuroprotective effect of IRJ in the okadaic acid (OKA)-induced Alzheimer's disease (AD) model in rats., Methods: In male Wistar rats, OKA was intracerebroventricularly (ICV) administered, and from day 7, they were treated orally with IRJ or memantine for 21 days. Spatial and recognition learning and memory were evaluated from days 27-34; employing the Morris water maze (MWM) and the novel object recognition tests (NORT), respectively. In vitro biochemical measurements were taken of the cholinergic system and oxidative stress markers. In silico docking was used to find the role of tau protein kinase and phosphatase in the pharmacological action., Results: In OKA-induced rats, IRJ decreased the escape latency and path length in MWM and increased the exploration time for novel objects and the discrimination index in NORT. ICV-OKA rats had higher free radicals and cytokines that caused inflammation and their level of free radical scavengers was back to normal with IRJ treatment. IRJ increased the level of acetylcholine and inhibited acetylcholinesterase. Moreover, the in silico docking study revealed the strong binding affinity of 10-hydroxy-2-decenoic acid (10-HDA), a bioactive constituent of IR, to the tau protein kinases and phosphatases., Conclusion: IRJ may serve as a nootropic agent in the treatment of dementia, and owing to its capacity to prevent oxidative stress and neuroinflammation, and increase cholinergic tone; it has the potential to be explored as a novel strategy for the treatment of dementia and AD. More studies may be needed to develop 10-HDA as a novel drug entity for AD., Competing Interests: Rahul N. Dubey, Sathiyanarayanan L, Sandeep Sankaran and Arulmozhi S declare that they have no conflict interests to declare that are relevant to the work reported in this manuscript., (© 2023 Center for Food and Biomolecules, National Taiwan University. Production and hosting by Elsevier Taiwan LLC.)

Diabetes Mellitus (DM) is the globe's common leading disease which is caused by high consumption of glucose. DM compiles groups of metabolic disorders which are characterized by inadequate secretion of insulin from pancreas, resulting in hyperglycemia condition. Many enzymes play a vital role in the metabolism of carbohydrate known as α-amylase and α-glucosidase which is calcium metalloenzyme that leads to breakdown of complex polysaccharides into glucose. To tackle this problem, search for newer antidiabetic drugs is the utmost need for the treatment and/or management of increasing diabetic burden. The inhibition of α-amylase and α-glucosidase is one of the effective therapeutic approaches for the development of antidiabetic therapeutics. The exhaustive literature survey has shown the importance of medicinally privileged triazole specifically 1,2,3-triazol and 1,2,4-triazoles scaffold tethered, fused and/or clubbed with other heterocyclic rings structures as promising agents for designing and development of novel antidiabetic therapeutics. Molecular hybrids namely pyridazine-triazole, pyrazoline-triazole, benzothiazole-triazole, benzimidazole-triazole, curcumin-triazole, (bis)coumarin-triazole, acridine-9-carboxamide linked triazole, quinazolinone-triazole, xanthone-triazole, thiazolo-triazole, thiosemicarbazide-triazole, and indole clubbed-triazole are few examples which have shown promising antidiabetic activity by inhibiting α-amylase and/or α-glucosidase. The present review summarizes the structure-activity relationship (SAR), enzyme inhibitory activity including IC 50 values, percentage inhibition, kinetic studies, molecular docking studies, and patents filed of the both scaffolds as alpha-amylase and alpha-glucosidase inhibitors, which may be used for further development of potent inhibitors against both enzymes., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

A 3D-supramolecular nickel integrated Ni-SDZ complex was synthesized using sodium salt of sulfadiazine as the ligand and nickel(II) acetate as the metal salt using a condensation process and slow evaporation approach to growing the single crystal. The metal complex was characterized for its composition, functional groups, surface morphology as well as complex 3D structure, by resorting to various analytical techniques. The interacting surface and stability as well as reactivity of the complex were carried out using the DFT platform. From ADMET parameters, human Intestinal Absorbance data revealed that the compound has the potential to be well absorbed, and also Ni-SDZ complex cannot cross the blood-brain barrier (BBB). Additionally, the complex's DNA binding affinity and in-vivo and in-vitro cytotoxic studies were explored utilizing UV-Vis absorbance titration, viscosity measurements, and S. pombe cells and brine shrimp lethality tests. In visible light radiation, the Ni-SDZ complex displayed exceptional photo-degradation characteristics of approximately 70.19% within 70 min against methylene blue (MB)., (© 2023. Springer Nature Limited.)

The novel discovered disease coronavirus popularly known as COVID-19 is caused due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and declared a pandemic by the World Health Organization (WHO). An early-stage detection of COVID-19 is crucial for the containment of the pandemic it has caused. In this study, a transfer learning-based COVID-19 screening technique is proposed. The motivation of this study is to design an automated system that can assist medical staff especially in areas where trained staff are outnumbered. The study investigates the potential of transfer learning-based models for automatically diagnosing diseases like COVID-19 to assist the medical force, especially in times of an outbreak. In the proposed work, a deep learning model, i.e., truncated VGG16 (Visual Geometry Group from Oxford) is implemented to screen COVID-19 CT scans. The VGG16 architecture is fine-tuned and used to extract features from CT scan images. Further principal component analysis (PCA) is used for feature selection. For the final classification, four different classifiers, namely deep convolutional neural network (DCNN), extreme learning machine (ELM), online sequential ELM, and bagging ensemble with support vector machine (SVM) are compared. The best performing classifier bagging ensemble with SVM within 385 ms achieved an accuracy of 95.7%, the precision of 95.8%, area under curve (AUC) of 0.958, and an F1 score of 95.3% on 208 test images. The results obtained on diverse datasets prove the superiority and robustness of the proposed work. A pre-processing technique has also been proposed for radiological data. The study further compares pre-trained CNN architectures and classification models against the proposed technique.

Canine parvovirus-2 (CPV-2), which emerged in 1978, is considered as the major viral enteric pathogen of the canine population. With the emergence of new antigenic variants and incidences of vaccine failure, CPV has become one of the dreaded diseases of the canines worldwide. The present study was undertaken in an organized kennel from North India to ascertain the molecular basis of the CPV outbreaks in the vaccinated dogs. 415 samples were collected over a 5year period (2008-2012). The outbreak of the disease was more severe in 2012 with high incidence of mortality in pups with pronounced clinical symptoms. Molecular typing based on the VP2 gene was carried out with the 11 isolates from different years and compared with the CPV prototype and the vaccine strains. All the isolates in the study were either new CPV-2a (2012 isolates) or new CPV-2b (2008 and 2011 isolates). There were amino acid mutations at the Tyr324Ile and at the Thr440Ala position in five isolates from 2012 indicating new CPV mutants spreading in India. The CPV vaccines used in the present study failed to generate protective antibody titer against heterogeneous CPV antigenic types. The findings were confirmed when the affected pups were treated with hyper-immune heterogeneous purified immunoglobulin's against CPV in dogs of different antigenic types., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: To assess the efficacy of 'Judders' as a technique reflecting adequacy of removal of ophthalmic viscoelastic device in cataract surgery., Design: Prospective, consecutive, single surgeon study., Participants: Cohort of 223 patients undergoing phacoemulsification., Methods: 'Judders' are periodic, abrupt, horizontal displacements of the intraocular lens causing balanced salt solution to displace retropseudophakic ophthalmic viscoelastic device. The number of 'Judders' was correlated with axial length, anterior chamber depth, and preoperative and postoperative intraocular pressure., Main Outcome Measures: Number of 'Judders', axial length, anterior chamber depth, day 1 postoperative intraocular pressure., Results: The mean number of 'Judders' was 3.2. There was a positive association between the number of 'Judders' and axial length, but not between number of 'Judders' and anterior chamber depth. Mean preoperative intraocular pressure was 14.5 mmHg; mean day 1 postoperative intraocular pressure was 15.6 mmHg. Intraocular pressure rose in 47% of cases. In six cases (5%), intraocular pressure rose greater than 10 mmHg (range 11-23 mmHg) from the preoperative level., Conclusions: Aspirating ophthalmic viscoelastic device with the irrigation/aspiration tip posterior to the intraocular lens may be associated with the risk of a posterior capsule tear. Maintaining the irrigation/aspiration tip anterior to the intraocular lens may offer a significant safety advantage. The number of 'Judders', usually 3-4, appears to be a safe and reliable end-point of complete ophthalmic viscoelastic device removal. There were significantly more 'Judders' in eyes with a longer axial length. The safety and efficacy of 'Judders' are reflected by the stable mean postoperative intraocular pressure., (© 2012 The Authors. Clinical and Experimental Ophthalmology © 2012 Royal Australian and New Zealand College of Ophthalmologists.)

Objective: To investigate the ideal correction of intraocular lens (IOL) power for sulcus implantation., Design: Retrospective, comparative case series., Participants: The records of 679 patients undergoing cataract surgery from June 2007 to June 2008 were reviewed., Intervention: Eyes in this series underwent phacoemulsification and IOL implantation with local anesthesia. Patients in our study population had their IOL power reduced by 0.5 or 1 diopter (D) from that calculated by the SRK-T formula for in-the-bag implantation. The IOL implanted was the foldable 3-piece acrylic Acrysof MA60AC (Alcon Laboratories Inc., Fort Worth, TX)., Main Outcome Measures: In each case, the difference between actual spherical equivalent (SE) refraction and that predicted by biometry using the SRK-T formula was calculated., Results: Posterior capsule tears requiring implantation of IOL in the ciliary sulcus occurred in 36 eyes. When comparing eyes in which the power was reduced by 0.5 D with those in which the reduction was 1.0 D, those with a power reduction of 1.0 D had significantly less unexpected error (0.49 vs. 1.01 D SE). After stratifying eyes by axial length (AL), we found higher unexpected refractive error in short eyes (<22 mm AL). Likewise, eyes with a predicted IOL power >25 D had a greater postoperative refractive error., Conclusions: This is the first comparative clinical review examining adjustment of power of the sulcus-implanted IOL. We found that the IOL power should be adjusted according to the measured AL and predicted IOL power. For patients with a predicted IOL power from 18 to 25 D, power should be reduced by at least 1 D; for lenses >25 D, power should be reduced by 1.5 to 2 D., (Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)