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Alzheimer's disease (AD) is a neurodegenerative disorder marked by significant loss of central cholinergic neurons. This progressive deterioration leads to cognitive dysfunction and impaired motor activity, culminating in the brain cell's death at the later stages of the disease. The approved drugs for AD are limited to providing symptomatic relief for an initial period due to the multifaceted etiology of the disease. Several studies have demonstrated that rivastigmine (RIV) is a selectively potent inhibitor of butyrylcholinesterase and devoid of antioxidant, Aβ, and tau protein aggregation inhibition and anti-inflammatory properties. Therefore, to address these issues associated with RIV, novel rivastigmine-based molecules were rationally designed, synthesized, and evaluated in various in-vitro and in-vivo AD models. In in-vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition studies revealed that 3q & 6e as promising leads (AChE, IC 50 1.72 ± 0.15, 0.91 ± 0.016 μM, BChE, IC 50 6.69 ± 0.28 μM, 1.19 ± 0.026 μM, for 3q & 6e, respectively). The computational studies (molecular docking and dynamics) further corroborated the in-vitro studies. Further, 3q and 6e were found to be potent antioxidants in the DPPH assay (IC 50 16.15 ± 1.05 & 15.17 ± 0.07 μM, for 3q & 6e, respectively). Interestingly, 3q, and 6e could effectively inhibit self-induced full-length tau and Aβ 1-42 aggregation. Treatment with 3q & 6e inhibited microglial activation by attenuating ROS release and mitochondrial damage. Further, 3q & 6e also suppressed NLRP3 inflammasome and NF-κB expression levels in microglial cells and halted the release of pro-inflammatory cytokines in human microglial cells. Finally, 3q & 6e were found to be efficacious in reversing the scopolamine-induced memory impairment in the Morris water maze test. The expression of various neuroprotection markers, such as BDNF and TRKB, was significantly overexpressed compared to the disease control group., 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 Elsevier Masson SAS. All rights reserved.)

Contemporary research evidence has corroborated a gradual loss of central cholinergic neurons in Alzheimer's Disease (AD). This progressive deterioration leads to cognitive dysfunction and impaired motor activity, culminating in the brain cell's death in the disease. The approved drugs for AD treatment can only offer relief from symptoms without addressing the underlying pathological hallmarks of the disease. To address the limitations associated with rivastigmine (RIV), a marketed drug for AD, a series of tryptamine derivatives was designed, synthesized, and evaluated in various in-vitro and in-vivo AD models. Enzyme inhibition studies identified compounds 6d and 6e as the lead molecules with potent inhibitors against AChE (6d, IC 50 : 0.99 ± 0.009 nM and 6e IC 50 : 7.97 ± 0.016 nM and BChE (6d, IC 50 : 27.79 ± 0.21 nM and 6e, IC 50 : 0.79 ± 0.005 nM), compared to the marketed drug Riv (AChE, IC 50 : 6630 ± 0.76 nM, BChE IC 50  = 91 ± 0.40 nM). The molecular docking and dynamics studies corroborated the enzyme inhibition studies. The PAMPA assay strongly suggested the BBB crossing ability of the lead molecules. Further, 6d and 6e demonstrated the capability to counteract oxidative stress and Aβ 1-42 in various in-vitro studies. Compound 6e exhibited remarkable radical scavenging activity in the DPPH assay (IC 50 : 22.91 ± 1.73 μM) compared to rivastigmine (% radical scavenging activity: 3.71 ± 0.09 at 200 μM). Interestingly, 6d and 6e exhibited promising activity in the AD Drosophila model by protecting eye phenotypes from degeneration induced by Aβ 1-42 toxicity and reduced mitochondrial and cellular oxidative stress in this model. Furthermore, upon oral administration, 6d and 6e could reverse scopolamine-induced amnesia by improving spatial and cognitive memory in mice at 0.3 and 0.5 mg/kg compared to rivastigmine at 3 mg/kg and were found to have potent ex-vivo anti-ChEs properties, which are correlated with the observed pro-cognitive effects in the Morris Water Maze, likely mediated through the inhibition of both cholinesterases. The expression of various neuroprotection markers, such as BDNF and TRKB, was significantly overexpressed compared to the disease control group., 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 Elsevier Masson SAS. All rights reserved.)

Objective This study aims to evaluate the MRI morphology of corpus callosum malformations and the associated anomalies frequently observed in a tertiary care center in northern India. Methods We conducted a retrospective cross-sectional study using MRI reports, images, and clinical records from January 2020 to July 2024. A total of 19 patients with corpus callosum agenesis or hypoplasia were identified, with 17 patients included after excluding those with incomplete records. We analyzed MRI findings for agenesis type (complete or partial), commissural abnormalities, midline anomalies, cortical abnormalities, and posterior fossa abnormalities. Statistical analysis was performed using chi-square tests to compare associations between complete and partial agenesis. Results Of the 17 patients, 52.9% had complete agenesis and 47.1% had partial agenesis. Complete agenesis was associated with higher rates of commissural involvement (44.4% vs. 12.5%), midline anomalies (22.2% vs. 0%), and Probst bundle formation (88.9% vs. 37.5%). Ventricular distortion was more common in complete agenesis (88.9% vs. 40%), and cortical malformations were also more prevalent (44.4% vs. 12.5%). Other anomalies included holoprosencephaly, Dandy-Walker malformation, and hypoxic-ischemic encephalopathy changes. Conclusion Complete agenesis of the corpus callosum is significantly associated with other commissural abnormalities, midline cysts, Probst bundle formation, ventricular distortions, and cortical malformations compared to partial agenesis. This study highlights the varied imaging presentations of corpus callosum malformations and their associated anomalies., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Saurya et al.)

Oxadiazoles an important heterocyclic scaffold of medicinal importance in the field of drug discovery. In the study, a library of oxadiazole based compounds was selected for screening against STAT-3 as anti-cancer target. STAT3 is a potential target of interest in cancer therapy. A total of 544 screened library of compounds was subjected to molecular docking against STAT-3 (6NJS and 6NQU). The compounds with good dock score and binding interations were further subjected to in-silico ADME analysis followed by toxicity estimation. A total of 141 hits were selected against 6NJS and 50 hits against 6NQU and further screened for kinetic properties and drug likeliness. The compounds were screened on the basis of physico-chemical properties, solubility, gastrointestinal absorption, BBB permeability, synthetic accessibility, Lipinski and other violations. Best compounds obtained after ADME analysis were further subjected for toxicity analysis. Carcinogenecity, mutagenicity, Ames and other important parameters were considered for toxicity based screening. The best leads thus obtained (compound 114 and 40) were further subjected to molecular dynamics against the respective target proteins. MD simulations were run to access the stability of C-114 and C-40 along with the dynamic behaviour of both complexes for about 100 ns and shows good stability with the proteins., Competing Interests: Conflict of interestThe authors declare no competing interests., (© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Type 2 diabetes, obesity, and several other metabolic diseases are all largely attributed to the problem known as insulin resistance. Diagnosing insulin resistance promptly and accurately is essential for adequately managing and intervening in metabolic disorders. Several diagnostic methods have been developed to assess insulin resistance. However, each method has advantages and disadvantages. The most precise test is the hyperinsulinemic-euglycemic clamp, which examines the direct impact of insulin on glucose uptake by tissues. However, it is primarily utilized in research due to its complexity and intrusiveness. Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and the Quantitative Insulin Sensitivity Check Index (QUICKI) are the second most used Insulin resistance tests in the clinical setup. These tests are based on measuring the fasting glucose and insulin levels. The Oral Glucose Tolerance Test (OGTT), Insulin tolerance test, and the Matsuda Index are further diagnostic procedures that shed light on insulin sensitivity. The improved techniques, such as the insulin suppression test and the minimal model analysis, provide substitutes for unique clinical circumstances. Additionally, including extra measurements with these tests, like waist circumference, lipid profiles, and inflammatory markers, can improve the evaluation of insulin resistance. In summary, identifying insulin resistance is essential for the early detection and treatment of various metabolic illnesses. To make educated judgments and improve patient care, healthcare workers should be aware of the different available diagnostic tests and how they are used in each situation. Insulin resistance detection and monitoring will require further study to improve current diagnostic approaches and create novel, less invasive techniques., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Fruits produce a wide variety of secondary metabolites of great economic value. Analytical measurement of the metabolites is tedious, time-consuming, and expensive. Additionally, metabolite concentrations vary greatly from tree to tree, making it difficult to choose trees for fruit collection. The current study tested whether deep learning-based models can be developed using fruit and leaf images alone to predict a metabolite's concentration class (high or low). We collected fruits and leaves (n = 1045) from neem trees grown in the wild across 0.6 million sq km, imaged them, and measured concentration of five metabolites (azadirachtin, deacetyl-salannin, salannin, nimbin and nimbolide) using high-performance liquid chromatography. We used the data to train deep learning models for metabolite class prediction. The best model out of the seven tested (YOLOv5, GoogLeNet, InceptionNet, EfficientNet_B0, Resnext_50, Resnet18, and SqueezeNet) provided a validation F1 score of 0.93 and a test F1 score of 0.88. The sensitivity and specificity of the fruit model alone in the test set were 83.52 ± 6.19 and 82.35 ± 5.96, and 79.40 ± 8.50 and 85.64 ± 6.21, for the low and the high classes, respectively. The sensitivity was further boosted to 92.67± 5.25 for the low class and 88.11 ± 9.17 for the high class, and the specificity to 100% for both classes, using a multi-analyte framework. We incorporated the multi-analyte model in an Android mobile App Fruit-In-Sight that uses fruit and leaf images to decide whether to 'pick' or 'not pick' the fruits from a specific tree based on the metabolite concentration class. Our study provides evidence that images of fruits and leaves alone can predict the concentration class of a secondary metabolite without using expensive laboratory equipment and cumbersome analytical procedures, thus simplifying the process of choosing the right tree for fruit collection., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Krishnan 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.)

Alzheimer's disease (AD) is the most prevalent cause of dementia and is characterized by low levels of acetyl and butyrylcholine, increased oxidative stress, inflammation, accumulation of metals, and aggregations of Aβ and tau proteins. Current treatments for AD provide only symptomatic relief without impacting the pathological hallmarks of the disease. In our ongoing efforts to develop naturally inspired novel multitarget molecules for AD, through extensive medicinal chemistry efforts, we have developed 13a , harboring the key functional groups to provide not only symptomatic relief but also targeting oxidative stress, able to chelate iron, inhibiting NLRP3, and Aβ 1-42 aggregation in various AD models. 13a exhibited promising anticholinesterase activity against AChE (IC 50 = 0.59 ± 0.19 μM) and BChE (IC 50 = 5.02 ± 0.14 μM) with excellent antioxidant properties in DPPH assay (IC 50 = 5.88 ± 0.21 μM) over ferulic acid (56.49 ± 0.62 μM). The molecular docking and dynamic simulations further corroborated the enzyme inhibition studies and confirmed the stability of these complexes. Importantly, in the PAMPA-BBB assay, 13a turned out to be a promising molecule that can efficiently cross the blood-brain barrier. Notably, 13a also exhibited iron-chelating properties. Furthermore, 13a effectively inhibited self- and metal-induced Aβ 1-42 aggregation. It is worth mentioning that 13a demonstrated no symptom of cytotoxicity up to 30 μM concentration in PC-12 cells. Additionally, 13a inhibited the NLRP3 inflammasome and mitigated mitochondrial-induced reactive oxygen species and mitochondrial membrane potential damage triggered by LPS and ATP in HMC-3 cells. 13a could effectively reduce mitochondrial and cellular reactive oxygen species (ROS) in the Drosophila model of AD. Finally, 13a was found to be efficacious in reversing memory impairment in a scopolamine-induced AD mouse model in the in vivo studies. In ex vivo assessments, 13a notably modulates the levels of superoxide, catalase, and malondialdehyde along with AChE and BChE. These findings revealed that 13a holds promise as a potential candidate for further development in AD management.

Chronic kidney disease-induced secondary hyperparathyroidism (CKD-SHPT) heightens fracture risk through impaired mineral homeostasis and elevated levels of uremic toxins (UTs), which in turn enhance bone remodeling. Etelcalcetide (Etel), a calcium-sensing receptor (CaSR) agonist, suppresses parathyroid hormone (PTH) in hyperparathyroidism to reduce excessive bone resorption, leading to increased bone mass. However, Etel's effect on bone quality, chemical composition, and strength is not well understood. To address these gaps, we established a CKD-SHPT rat model and administered Etel at a human-equivalent dose concurrently with disease induction. The effects on bone and mineral homeostasis were compared with a CKD-SHPT (vehicle-treated group) and a control group (rats without SHPT). Compared with vehicle-treated CKD-SHPT rats, Etel treatment improved renal function, reduced circulating UT levels, improved mineral homeostasis parameters, decreased PTH levels, and prevented mineralization defects. The upregulation of mineralization-promoting genes by Etel in CKD-SHPT rats might explain its ability to prevent mineralization defects. Etel preserved both trabecular and cortical bones with attendant suppression of osteoclast function, besides increasing mineralization. Etel maintained the number of viable osteocytes to the control level, which could also contribute to its beneficial effects on bone. CKD-SHPT rats displayed increased carbonate substitution of matrix and mineral, decreased crystallinity, mineral-to-matrix ratio, and collagen maturity, and these changes were mitigated by Etel. Further, Etel treatment prevented CKD-SHPT-induced deterioration in bone strength and mechanical behavior. Based on these findings, we conclude that in CKD-SHPT rats, Etel has multiscale beneficial effects on bone that involve remodeling suppression, mineralization gene upregulation, and preservation of osteocytes., Competing Interests: Declaration of competing interest There is no known conflict of interest related to this research work and no competing financial interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Alzheimer's disease (AD) is a neurodegenerative disease characterized by Aβ plaques and neurofibrillary tangles. Chronic inflammation and synaptic dysfunction lead to disease progression and cognitive decline. Small extracellular vesicles (sEVs) are implicated in AD progression by facilitating the spread of pathological proteins and inflammatory cytokines. This study investigates synaptic dysfunction and neuroinflammation protein markers in plasma-derived sEVs (PsEVs), their association with Amyloid-β and tau pathologies, and their correlation with AD progression., Methods: A total of 90 [AD = 35, mild cognitive impairment (MCI) = 25, and healthy age-matched controls (AMC) = 30] participants were recruited. PsEVs were isolated using a chemical precipitation method, and their morphology was characterized by transmission electron microscopy. Using nanoparticle tracking analysis, the size and concentration of PsEVs were determined. Antibody-based validation of PsEVs was done using CD63, CD81, TSG101, and L1CAM antibodies. Synaptic dysfunction and neuroinflammation were evaluated with synaptophysin, TNF-α, IL-1β, and GFAP antibodies. AD-specific markers, amyloid-β (1-42), and p-Tau were examined within PsEVs using Western blot and ELISA., Results: Our findings reveal higher concentrations of PsEVs in AD and MCI compared to AMC (p < 0.0001). Amyloid-β (1-42) expression within PsEVs is significantly elevated in MCI and AD compared to AMC. We could also differentiate between the amyloid-β (1-42) expression in AD and MCI. Similarly, PsEVs-derived p-Tau exhibited elevated expression in MCI compared with AMC, which is further increased in AD. Synaptophysin exhibited downregulated expression in PsEVs from MCI to AD (p = 0.047) compared to AMC, whereas IL-1β, TNF-α, and GFAP showed increased expression in MCI and AD compared to AMC. The correlation between the neuropsychological tests and PsEVs-derived proteins (which included markers for synaptic integrity, neuroinflammation, and disease pathology) was also performed in our study. The increased number of PsEVs correlates with disease pathological markers, synaptic dysfunction, and neuroinflammation., Conclusions: Elevated PsEVs, upregulated amyloid-β (1-42), and p-Tau expression show high diagnostic accuracy in AD. The downregulated synaptophysin expression and upregulated neuroinflammatory markers in AD and MCI patients suggest potential synaptic degeneration and neuroinflammation. These findings support the potential of PsEV-associated biomarkers for AD diagnosis and highlight synaptic dysfunction and neuroinflammation in disease progression., (© 2024. The Author(s).)

Breast cancer, a leading cause of female mortality due to delayed detection owing to asymptomatic nature and limited early diagnostic tools, was investigated using a multi-modal approach. Plasma-derived small EVs from breast cancer patients (BrCa, n = 74) and healthy controls (HC, n = 30) were analyzed. Small EVs (n = 104), isolated through chemical precipitation, underwent characterization via transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). Validation involved antibody-based tests (TSG101, CD9, CD81, CD63). Infrared spectra of small EVs were obtained, revealing significant differences in lipid acyl chains, particularly in the C-H stretching of CH3. The study focused on the lipid region (3050-2900 cm -1 ), identifying peaks (3015 cm -1 , 2960 cm -1 , 2929 cm -1 ) as distinctive lipid characteristics. Spectroscopic lipid-to-lipid ratios [(I3015/I2929), (I2960/I2929)] emerged as prominent breast cancer markers. Exploration of protein, nucleic acid, and carbohydrate ratios indicated variations in alpha helices, asymmetric C-H stretching vibrations, and C-O stretching at 1033 cm -1 . Principal component analysis (PCA) successfully differentiated BrCa and HC small EVs, and heatmap analysis and receiver operating characteristic (ROC) curve evaluations underscored the discriminatory power of lipid ratios. Notably, (I2960/I2929) exhibited 100% sensitivity and specificity, highlighting its potential as a robust BrCa sEV marker for breast cancer detection., (© 2024. The Author(s).)

Alzheimer's disease (AD) is the most common cause of dementia, which arises due to low levels of acetyl and butyrylcholines, an increase in oxidative stress, inflammation, metal dyshomeostasis, Aβ and tau aggregations. The currently available drugs for AD treatment can provide only symptomatic relief without interfering with pathological hallmarks of the disease. In our ongoing efforts to develop naturally inspired novel multifunctional molecules for AD, systematic SAR studies on EJMC-4e were caried out to improve its multifunctional properties. The rigorous medicinal efforts led to the development of 12o , which displayed a 15-fold enhancement in antioxidant properties and a 2-fold increase in the activity against AChE and BChE over EJMC-4e . Molecular docking and dynamics studies revealed the binding sites and stability of the complex of 12o with AChE and BChE. The PAMPA-BBB assay clearly demonstrated that 12o can easily cross the blood-brain barrier. Interestingly, 12o also expresses promising metal chelation activity, while EJMC-4e was found to be devoid of this property. Further, 12o inhibited metal-induced or self Aβ 1-42 aggregation. Observing the neuroprotection ability of 12o against H 2 O 2 -induced oxidative stress in the PC-12 cell line is noteworthy. Furthermore, 12o also inhibited NLRP3 inflammasome activation and attenuated mitochondrial-induced ROS and MMP damage caused by LPS and ATP in HMC-3 cells. In addition, 12o is able to effectively reduce mitochondrial and cellular oxidative stress in the AD Drosophila model. Finally, 12o could reverse memory impairment in the scopolamine-induced AD mice model, as evident through in vivo and ex vivo studies. These findings suggest that this compound may act as a promising candidate for further improvement in the management of AD.

The survival rate over a five-year period for rare pancreatic neuroendocrine tumors (PanNET) is notably lower compared to other neuroendocrine tumors due to late-stage detection, which is a consequence of the absence of suitable diagnostic markers; therefore, there exists a critical need for an early-stage biomarker-specific to PanNETs. This study introduces a novel approach, investigating the impact of small extracellular vesicles (sEV) in PanNET growth and metastasis. As proof of concept, this study shows a correlation between sEV concentration in controls and PanNET. Notably, higher sEV concentrations were observed in PanNETs than in controls (p < 0.0001) with a sensitivity of 100%. Further, apparent differences were observed in the sEV concentrations between controls and grades 1 PanNET (p = 0.005). The expression of sEV markers was confirmed using CD63, TSG101, CD9, Flotillin-1, and GAD65 antibodies. Additionally, the expression of cancer marker BIRC2/cIAP1 (p = 0.002) and autophagy marker Beclin-1 (p = 0.02) were observed in plasma-derived sEVs and PanNET tissue. This study represents the first to indicate the increased secretion of sEV in PanNET patients' blood plasma, proposing potential function of sEV as a new biomarker for early-stage PanNET detection., Competing Interests: 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., (© 2024 The Authors. Published by Elsevier Ltd.)

Vascular dysfunction contributes to the development of osteopenia in hypertensive patients, as decreased blood supply to bones results in tissue damage and dysfunction. The effect of anti-hypertensive medicines on bone mass in hypertensive individuals is inconclusive because of the varied mechanism of their action, and suggests that reducing blood pressure (BP) alone is insufficient to enhance bone mass in hypertension. Pentoxifylline (PTX), a hemorheological drug, improves blood flow by reducing blood viscosity and angiogenesis, also has an osteogenic effect. We hypothesized that improving vascular function is critical to increasing bone mass in hypertension. To test this, we screened various anti-hypertensive drugs for their in vitro osteogenic effect, from which timolol and hydralazine were selected. In adult female spontaneously hypertensive rats (SHRs), timolol and hydralazine did not improve vascular function and bone mass, but PTX improved both. In female SHR animals, PTX restored bone mass, strength and mineralization, up to the level of normotensive control rats. In addition, we observed lower blood vasculature in the femur of adult SHR animals, and PTX restored them. PTX also restored the bone vascular and angiogenesis parameters that had been impaired in OVX SHR compared to sham SHR. This study demonstrates the importance of vascular function in addition to increased bone mass for improving bone health as achieved by PTX without affecting BP, and suggests a promising treatment option for osteoporosis in hypertensive patients, particularly at-risk postmenopausal women., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Urinary small extracellular vesicles or exosomes (uEVs) source could be an emerging trove of biomarkers in coronary artery disease (CAD). It is a chronic inflammatory disease having a long asymptomatic phase of fatty-fibrous development in arteries leading to angina, myocardial infarction, and death. Our study was aimed at identifying differential protein expression profiling of uEVs in CAD. We collected urine samples of CAD patients (n = 41) age 18-65 years and gender matched healthy controls (n = 41). We isolated uEVs using differential ultracentrifugation. Further, uEV samples were characterized by western blotting exosome markers (Flotillin, TSG, CD63, and CD9), nano tracking analysis, and transmission and scanning electron microscopy. A total of 508 proteins were identified by iTRAQ-based mass spectrometry. We observed protein expression levels of AZGP1, SEMG1/2, ORM1, IGL, SERPINA5, HSPG2, prosaposin, gelsolin, and CD59 were upregulated, and UMOD, KNG1, AMBP, prothrombin, and TF were downregulated. Protein-protein interactions, gene ontology and pathway analysis were performed to functionally annotate identified uEVs proteins. A novel uEVs differential protein signature is shown. On validating UMOD protein by ELISA in two clinically different CAD, stable-CAD patients had lower levels than healthy controls whereas recent myocardial infarction patients had lowest. Our findings suggest UMOD importance as early diagnostic biomarker. SIGNIFICANCE: Coronary artery disease is a chronic inflammatory disease caused by gradual deposition of cholesterol and fat along with other proteins to develop plaque inside arteries. This further leads to blockage of artery, heart attack and death. There are no identifiable early biomarkers to diagnose this. For the first time, we have identified the differentially expressed proteins isolated from non-invasive uEV of CAD patients compared to healthy controls by using MS Orbitrap and iTRAQ labelling of peptides. We have identified decreased levels of UMOD protein in CAD. These findings have been confirmed by ELISA. Furthermore, the levels of UMOD were observed as more highly decreased in recent myocardial infarction CAD patients, indicating the importance of this protein as an early diagnostic biomarker. Conclusively, our study represents a non-invasive urinary EVs trove of differentially expressed proteins in CAD. This will form a groundwork for understanding the pathophysiology of CAD and will help in future translational research utilizing uEVs., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2023. Published by Elsevier B.V.)

The process of ferroptosis, a recently identified form of regulated cell death (RCD) is associated with the overloading of iron species and lipid-derived ROS accumulation. Ferroptosis is induced by various mechanisms such as inhibiting system Xc, glutathione depletion, targeting excess iron, and directly inhibiting GPX4 enzyme. Also, ferroptosis inhibition is achieved by blocking excessive lipid peroxidation by targeting different pathways. These mechanisms are often related to the pathophysiology and pathogenesis of diseases like cancer and Alzheimer's. Fundamentally distinct from other forms of cell death, such as necrosis and apoptosis, ferroptosis differs in terms of biochemistry, functions, and morphology. The mechanism by which ferroptosis acts as a regulatory factor in many diseases remains elusive. Studying the activation and inhibition of ferroptosis as a means to mitigate the progression of various diseases is a highly intriguing and actively researched topic. It has emerged as a focal point in etiological research and treatment strategies. This review systematically summarizes the different mechanisms involved in the inhibition and induction of ferroptosis. We have extensively explored different agents that can induce or inhibit ferroptosis. This review offers current perspectives on recent developments in ferroptosis research, highlighting the disease's etiology and presenting references to enhance its understanding. It also explores new targets for the treatment of cancer and Alzheimer's disease., 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 © 2023 Elsevier Ltd. All rights reserved.)

Pancreatic Neuroendocrine tumors (PanNET) are challenging to diagnose and often detected at advanced stages due to a lack of specific and sensitive biomarkers. This study utilized proteomics as a valuable approach for cancer biomarker discovery; therefore, mass spectrometry-based proteomic profiling was conducted on plasma samples from 12 subjects (3 controls; 5 Grade I, 4 Grade II PanNET patients) to identify potential proteins capable of effectively distinguishing PanNET from healthy controls. Data are available via ProteomeXchange with the identifier PXD045045. 13.2% of proteins were uniquely identified in PanNET, while 60% were commonly expressed in PanNET and controls. 17 proteins exhibiting significant differential expression between PanNET and controls were identified with downstream analysis. Further, 5 proteins (C1QA, COMP, HSP90B1, ITGA2B, and FN1) were selected by pathway analysis and were validated using Western blot analysis. Significant downregulation of C1QA (p = 0.001: within groups, 0.03: control vs. grade I, 0.0013: grade I vs. grade II) and COMP (p = 0.011: within groups, 0.019: control vs grade I) were observed in PanNET Grade I & II than in controls. Subsequently, ELISA on 38 samples revealed significant downregulation of C1QA and COMP with increasing disease severity. This study shows the potential of C1QA and COMP in the early detection of PanNET, highlighting their role in the search for early-stage (Grade-I and Grade-II) diagnostic markers and therapeutic targets for PanNET., (© 2023. The Author(s).)

Background: Parkinson's disease (PD) is an increasingly common neurodegenerative condition, which causes movement dysfunction and a broad range of non-motor symptoms. There is no molecular or biochemical diagnosis test for PD. The miRNAs are a class of small non-coding RNAs and are extensively studied owing to their altered expression in pathological states and facile harvesting and analysis techniques., Methods: A total of 48 samples (16 each of PD, aged-matched, and young controls) were recruited. The small extracellular vesicles (sEVs) were isolated and validated using Western blot, transmission electron microscope, and nanoparticle tracking analysis. Small RNA isolation, library preparation, and small RNA sequencing followed by differential expression and targeted prediction of miRNA were performed. The real-time PCR was performed with the targeted miRNA on PD, age-matched, and young healthy control of plasma and plasma-derived sEVs to demonstrate their potential as a diagnostic biomarker., Results: In RNA sequencing, we identified 14.89% upregulated (fold change 1.11 to 11.04, p < 0.05) and 16.54% downregulated (fold change -1.04 to -7.28, p < 0.05) miRNAs in PD and controls. Four differentially expressed miRNAs (miR-23b-3p, miR-29a-3p, miR-19b-3p, and miR-150-3p) were selected. The expression of miR-23b-3p was "upregulated" ( p = 0.002) in plasma, whereas "downregulated" ( p = 0.0284) in plasma-derived sEVs in PD than age-matched controls. The ROC analysis of miR-23b-3p revealed better AUC values in plasma (AUC = 0.8086, p = 0.0029) and plasma-derived sEVs (AUC = 0.7278, p = 0.0483) of PD and age-matched controls., Conclusion: We observed an opposite expression profile of miR-23b-3p in PD and age-matched healthy control in plasma and plasma-derived sEV fractions, where the expression of miR-23b-3p is increased in PD plasma while decreased in plasma-derived sEV fractions. We further observed the different miR-23b-3p expression profiles in young and age-matched healthy control., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Rai, Bharti, Singh, Rastogi, Rani, Sharma, Gorai, Rani, Verma, Reddy, Modi, Inampudi, Pandey, Yadav, Rajan, Nikolajeff and Kumar.)

Lake sediments can provide valuable insights into anthropogenic disturbances such as intensive aquaculture and land use changes. These disturbances often manifest as elevated levels of nutrients and elements within the sediments. This paper uses several analytical techniques, i.e., FTIR (Fourier-transform infrared spectroscopy), XRD (X-ray diffraction), EDS (energy-dispersive X-ray spectroscopy), and SEM (scanning electron microscopy), to examine the elemental constituents of lake sediments, along with their relative mineral abundances and surface morphology. The selected freshwater lakes are from the Central Gangetic Plain. The analysis provides a "fingerprint" of geogenic and biogenic mineral constituents of the sediments. Physicochemical, mineralogical, and elemental analysis shows that intensive aquaculture activities in lake alter the sediment chemistry as evidenced by the increase in pH, organic carbon, organic matter, and total phosphorus which is not observed in the lake where aquaculture is prohibited. Freshwater lake sediment is characterized by a high content of biogenic silica and carbonate minerals. The variations in sediment nutrients and mineral fluxes of the selected lakes are mainly attributed to diverse anthropogenic pressures, differences in lake productivity, and the overall ecological condition of the lakes. In the selected three lakes, major variation was reported in the autochthonous sediments in comparison to the allochthonous sediments. The study concludes that catchment and biotic deposit variations in the lakes cannot be evened out by in-lake mixing mechanisms due to variations in the terrigenous and pelagic deposits of the lake. The results highlight the importance of studying annual fluctuations and spatial variations in geogenic and biogenic mineral particle fluxes in lakes. Such investigations provide valuable insights into the annual dynamics of minerals within lakes, contributing to a more comprehensive understanding of their behavior and distribution., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Parkinson's disease is generally asymptomatic at earlier stages. At an early stage, there is an extensive progression in the neuropathological hallmarks, although, at this stage, diagnosis is not possible with currently available diagnostic methods. Therefore, the pressing need is for susceptibility risk biomarkers that can aid in better diagnosis and therapeutics as well can objectively serve to measure the endpoint of disease progression. The role of small extracellular vesicles (sEV) in the progression of neurodegenerative diseases could be potent in playing a revolutionary role in biomarker discovery., Methods: In our study, the salivary sEV were efficiently isolated by chemical precipitation combined with ultrafiltration from subjects (PD = 70, healthy controls = 26, and prodromal PD = 08), followed by antibody-based validation with CD63, CD9, GAPDH, Flotillin-1, and L1CAM. Morphological characterization of the isolated sEV through transmission electron microscopy. The quantification of sEV was achieved by fluorescence (lipid-binding dye-labeled) nanoparticle tracking analysis and antibody-based (CD63 Alexa fluor 488 tagged sEV) nanoparticle tracking analysis. The total alpha-synuclein (α-syn Total ) in salivary sEVs cargo was quantified by ELISA. The disease severity staging confirmation for n = 18 clinically diagnosed Parkinson's disease patients was done by 99m Tc-TRODAT-single-photon emission computed tomography., Results: We observed a significant increase in total sEVs concentration in PD patients than in the healthy control (HC), where fluorescence lipid-binding dye-tagged sEV were observed to be higher in PD (p = 0.0001) than in the HC using NTA with a sensitivity of 94.34%. In the prodromal PD cases, the fluorescence lipid-binding dye-tagged sEV concentration was found to be higher (p = 0.008) than in HC. This result was validated through anti-CD63 tagged sEV (p = 0.0006) with similar sensitivity of 94.12%. We further validated our findings with the ELISA based on α-syn Total concentration in sEV, where it was observed to be higher in PD (p = 0.004) with a sensitivity of 88.24%. The caudate binding ratios in 99m Tc-TRODAT-SPECT represent a positive correlation with sEV concentration (r = 0.8117 with p = 0.0112)., Conclusions: In this study, for the first time, we have found that the fluorescence-tagged sEV has the potential to screen the progression of disease with clinically acceptable sensitivity and can be a potent early detection method for PD., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Introduction: We investigated the effects of hormonal and non-hormonal oral contraceptives (OCs) on bone mass, mineralization, composition, mechanical properties, and metabolites in pubertal female SD rats., Methods: OCs were given for 3-, and 7 months at human equivalent doses. The combined hormonal contraceptive (CHC) was ethinyl estradiol and progestin, whereas the non-hormonal contraceptive (NHC) was ormeloxifene. MicroCT was used to assess bone microarchitecture and BMD. Bone formation and mineralization were assessed by static and dynamic histomorphometry. The 3-point bending test, nanoindentation, FTIR, and cyclic reference point indentation (cRPI) measured the changes in bone strength and material composition. Bone and serum metabolomes were studied to identify potential biomarkers of drug efficacy and safety and gain insight into the underlying mechanisms of action of the OCs., Results: NHC increased bone mass in the femur metaphysis after 3 months, but the gain was lost after 7 months. After 7 months, both OCs decreased bone mass and deteriorated trabecular microarchitecture in the femur metaphysis and lumbar spine. Also, both OCs decreased the mineral: matrix ratio and increased the unmineralized matrix after 7 months. After 3 months, the OCs increased carbonate: phosphate and carbonate: amide I ratios, indicating a disordered hydroxyapatite crystal structure susceptible to resorption, but these changes mostly reversed after 7 months, indicating that the early changes contributed to demineralization at the later time. In the femur 3-point bending test, CHC reduced energy storage, resilience, and ultimate stress, indicating increased susceptibility to micro-damage and fracture, while NHC only decreased energy storage. In the cyclic loading test, both OCs decreased creep indentation distance, but CHC increased the average unloading slope, implying decreased microdamage risk and improved deformation resistance by the OCs. Thus, reduced bone mineralization by the OCs appears to affect bone mechanical properties under static loading, but not its cyclic loading ability. When compared to an age-matched control, after 7 months, CHC affected 24 metabolic pathways in bone and 9 in serum, whereas NHC altered 17 in bone and none in serum. 6 metabolites were common between the serum and bone of CHC rats, suggesting their potential as biomarkers of bone health in women taking CHC., Conclusion: Both OCs have adverse effects on various skeletal parameters, with CHC having a greater negative impact on bone strength., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Porwal, Sharma, Kumar, Tomar, Sadhukhan, Rajput, Kulkarni, Shrivastava, Kumar and Chattopadhyay.)

Lung cancer is one of the most common and deadly types of cancer worldwide, and the epidermal growth factor receptor (EGFR) has emerged as a promising therapeutic target for the treatment of this disease. In this study, we designed a library of 1840 benzofuran-1,2,3-triazole hybrids and conducted pharmacophore-based screening to identify potential EGFR inhibitors. The 20 identified compounds were further evaluated using molecular docking and molecular dynamics simulations to understand their binding interactions with the EGFR receptor. In-silico ADME and toxicity studies were also performed to assess their drug-likeness and safety profiles. The results of this study showed the benzofuran-1,2,3-triazole hybrids BENZ-0454, BENZ-0143, BENZ-1292, BENZ-0335, BENZ-0332, and BENZ-1070 dock score of - 10.2, - 10, - 9.9, - 9.8, - 9.7, - 9.6, while reference molecule - 7.9 kcal/mol for EGFR (PDB ID: 4HJO) respectively. The molecular docking and molecular dynamics simulations revealed that the identified compounds formed stable interactions with the active site of the receptor, indicating their potential as inhibitors. The in-silico ADME and toxicity studies suggested that the compounds had good pharmacokinetic and safety profiles, further supporting their potential as therapeutic agents. Finally, performed DFT studies on the best-selected ligands to gain further insights into their electronic properties. The findings of this study provide important insights into the potential of benzofuran-1,2,3-triazole hybrids as promising EGFR inhibitors for the treatment of lung cancer. Overall, this study provides a valuable starting point for the development of novel EGFR inhibitors with improved efficacy and safety profiles., Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-023-00157-1., Competing Interests: Conflict of interestThe authors confirm that there are no known conflicts of interest associated with this publication and no significant financial support for this work that could have influenced its outcome., (© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Through comparative analyses using BLASTp and BLASTn of the 25 target sequences, our research identified two unique post-transcriptional modifiers, Rv1509 and Rv2231A, which serve as distinctive and characteristic proteins of M.tb - the Signature Proteins. Here, we have characterized these two signature proteins associated with pathophysiology of M.tb which may prove to be therapeutically important targets. Dynamic Light Scattering and Analytical Gel Filtration Chromatography exhibited that Rv1509 exists as a monomer while Rv2231A as a dimer in solution. Secondary structures were determined using Circular Dichroism and further validated through Fourier Transform Infrared spectroscopy. Both the proteins are capable of withstanding a wide range of temperature and pH variations. Fluorescence spectroscopy based binding affinity experiments showed that Rv1509 binds to iron and may promote organism growth by chelating iron. In the case of Rv2231A, a high affinity for its substrate RNA was observed, which is facilitated in presence of Mg 2+ suggesting it might have RNAse activity, supporting the prediction through in-silico studies. This is the first study on biophysical characterization of these two therapeutically important proteins, Rv1509 and Rv2231A, providing important insights into their structure -function correlations which are crucial for development of new drugs/ early diagnostics tools targeting these proteins., Competing Interests: Declaration of competing interest The authors declare that they have NO conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Mesenchymal stem/stromal cell (MSC) spheroids generated in a three-dimensional (3D) culture system serve as a surrogate model that maintain stem cell characteristics since these mimic the in vivo behavior of cells and tissue more closely. Our study involved a detailed characterization of the spheroids generated in ultra-low attachment flasks. The spheroids were evaluated and compared for their morphology, structural integrity, viability, proliferation, biocomponents, stem cell phenotype and differentiation abilities with monolayer culture derived cells (2D culture). The in-vivo therapeutic efficacy of DPSCs derived from 2D and 3D culture was also assessed by transplanting them in an animal model of the critical-sized calvarial defect. DPSCs formed compact and well-organized multicellular spheroids when cultured in ultra-low attachment condition with superior stemness, differentiation, and regenerative abilities than monolayer cells. They maintained lower proliferative state and showed marked difference in the cellular biocomponents such as lipid, amide and nucleic acid between DPSCs from 2D and 3D cultures. The scaffold-free 3D culture efficiently preserves DPSCs intrinsic properties and functionality by maintaining them in the state close to the native tissues. The scaffold free 3D culture methods allow easy collection of a large number of multicellular spheroids of DPSCs and therefore, this can be adopted as a feasible and efficient method of generating robust spheroids for various in-vitro and in-vivo therapeutic 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 © 2023 Elsevier Ltd. All rights reserved.)

The autonomous robot has been the attraction point among robotic researchers since the last decade by virtue of increasing demand of automation in defence and intelligent industries. In the current research, a modified flow direction optimization algorithm (MFDA) and firefly algorithm (FA) are hybridized and implemented on wheeled robots to encounter multi-target trajectory optimization with smooth navigation by negotiating obstacles present within the workspace. Here, a hybrid algorithm is adopted for designing the controller with consideration of navigational parameters. A Petri-Net controller is also aided with the developed controller to resolve any conflict during navigation. The developed controller has been investigated on WEBOTS and MATLAB simulation environments coupled with real-time experiments by considering Khepera-II robot as wheeled robot. Single robot- multi-target, multiple robot single target and multiple robots-multiple target problems are tackled during the investigation. The outcomes of simulation are verified through real-time experimental outcomes by comparing results. Further, the proposed algorithm is tested for its suitability, precision, and stability. Finally, the developed controller is tested against existing techniques for authentication of proposed technique, and significant improvements of an average 34.2% is observed in trajectory optimization and 70.6% in time consumption., 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 © 2023 ISA. Published by Elsevier Ltd. All rights reserved.)

Cancer is a cause of high deaths worldwide and also a huge burden for the health system. Cancer cells have unique properties such as a high rate of proliferation, self-renewal, metastasis, and treatment resistance, therefore, the development of novel diagnoses of cancers is a tedious task. Exosomes are secreted by virtually all cell types and have the ability to carry a multitude of biomolecules crucial for intercellular communication, hence, contributing a crucial part in the onset and spread of cancer. These exosomal components can be utilized in the development of markers for diagnostic and prognostic purposes for various cancers. This review emphasized primarily the following topics: exosomes structure and functions, isolation and characterization strategies of exosomes, the role of exosomal contents in cancer with a focus in particular on noncoding RNA and protein, exosomes, and the cancer microenvironment interactions, cancer stem cells, and tumor diagnosis and prognosis based on exosomes., 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 © 2023. Published by Elsevier B.V.)

Introduction: The study evaluates the levels of matrix metalloprotease-8 (MMP-8), and Cathepsin-K (CatK) in peri-implant crevicular fluid (PICF) among patients with immediate loaded (IL) and delayed-loaded (DL) implants at different time points to know the inflammation and osteogenic status., Methods: The study population consisted of two groups (n = 25, each group) with a mean age of 28.7 ± 3.5 years, and PICF was collected. MMP-8 and CatK levels were quantified through ELISA., Results: We observed the concentrations of inflammatory markers (MMP-8 and CatK) at three time points in the IL and DL groups. The mean concentration of MMP-8 in the IL group was 9468 ± 1230 pg/mL, 5547 ± 1088 pg/mL, and 7248 ± 1396 pg/mL at 2 weeks, 3 months, and 12 months, respectively; while in the DL group was 10 816 ± 779.7 pg/mL, 9531 ± 1245 pg/mL, and 9132 ± 1265 pg/mL at 2 weeks, 3 and 12 months, respectively. The mean concentration of Cat-K in the IL group was observed at 422.1 ± 36.46 pg/mL, 242.9 ± 25.87 pg/mL, and 469 ± 75.38 pg/mL at 2 weeks, 3, and 12 months, whereas in the DL group was 654.6 ± 152.9 pg/mL, 314.7 ± 28.29 pg/mL, and 539.8 ± 115.1 pg/mL at 2 weeks, 3 months and 12 months, respectively., Conclusion: In this study, the levels of CatK and MMP-8 levels decline at 12 months in both groups, and the IL group shows lower values compared to the DL group; however, no significant changes were observed after analyses were adjusted for multiple comparisons (p > 0.025). Therefore, there is not much difference observed in the inflammation process between immediate and delayed loading. (Clinical trial identifier: CTRI/2017/09/009668)., (© 2023 The Authors. Clinical Implant Dentistry and Related Research published by Wiley Periodicals LLC.)

Introduction: In obese humans, Coleus forskohlii root extract (CF) protects against weight gain owing to the presence of forskolin, an adenylate cyclase (AC) activator. As AC increases intracellular cyclic adenosine monophosphate (cAMP) levels in osteoblasts that has an osteogenic effect, we thus tested the skeletal effects of a standardized CF (CFE) in rats., Methods: Concentrations of forskolin and isoforskolin were measured in CFE by HPLC. CFE and forskolin (the most abundant compound present in CFE) were studied for their osteogenic efficacy in vitro by alkaline phosphatase (ALP), cAMP and cyclic guanosine monophosphate (cGMP) assays. Femur osteotomy model was used to determine the osteogenic dose of CFE. In growing rats, CFE was tested for its osteogenic effect in intact bone. In adult ovariectomized (OVX) rats, we assessed the effect of CFE on bone mass, strength and material. The effect of forskolin was assessed in vivo by measuring the expression of osteogenic genes in the calvarium of rat pups., Results: Forskolin content in CFE was 20.969%. CFE increased osteoblast differentiation and intracellular cAMP and cGMP levels in rat calvarial osteoblasts. At 25 mg/kg (half of human equivalent dose), CFE significantly enhanced calcein deposition at the osteotomy site. In growing rats, CFE promoted modeling-directed bone formation. In OVX rats, CFE maintained bone mass and microarchitecture to the level of sham-operated rats. Moreover, surface-referent bone formation in CFE treated rats was significantly increased over the OVX group and was comparable with the sham group. CFE also increased the pro-collagen type-I N-terminal propeptide: cross-linked C-telopeptide of type-I collagen (PINP : CTX-1) ratio over the OVX rats, and maintained it to the sham level. CFE treatment decreased the OVX-induced increases in the carbonate-to-phosphate, and carbonate-to-amide-I ratios. CFE also prevented the OVX-mediated decrease in mineral crystallinity. Nanoindentation parameters, including modulus and hardness, were decreased by OVX but CFE maintained these to the sham levels. Forskolin stimulated ALP, cAMP and cGMP in vitro and upregulated osteogenic genes in vivo ., Conclusion: CFE, likely due to the presence of forskolin displayed a bone-conserving effect via osteogenic and anti-resorptive mechanisms resulting in the maintenance of bone mass, microarchitecture, material, and strength., Competing Interests: Authors AG and LH were employed by Pharmanza Herbal Pvt. Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kulkarni, Sharma, Porwal, Rajput, Sadhukhan, Singh, Singh, Baranwal, Kumar, Girme, Pandey, Singh, Sashidhara, Kumar, Hingorani and Chattopadhyay.)

Neurodegenerative diseases are a set of progressive and currently incurable diseases that are primarily caused by neuron degeneration. Neurodegenerative diseases often lead to cognitive impairment and dyskinesias. It is now well recognized that molecular events precede the onset of clinical symptoms by years. Over the past decade, intensive research attempts have been aimed at the early diagnosis of these diseases. Recently, exosomes have been shown to play a pivotal role in the occurrence and progression of many diseases including cancer and neurodegenerative diseases. Additionally, because exosomes can cross the blood-brain barrier, they may serve as a diagnostic tool for neural dysfunction. In this review, we detail the mechanisms and current challenges of these diseases, briefly review the role of exosomes in the progression of neurodegenerative diseases, and propose a novel strategy based on salivary neuronal exosomes and nanoparticle tracking analysis that could be employed for screening the early onset of neurodegenerative diseases., (© 2023. The Author(s).)

Trypanosoma evansi, a hemoflagellate protozoan, leads to wasting disease, surra in livestock animals causing huge economic losses. Currently, the preferred assay for surra diagnosis is whole cell lysate (WCL) based ELISA, which requires the use of rodents for WCL preparation. To avoid use of laboratory animals, we used recombinant DNA technology to express T. evansi invariable surface glycoprotein (ISG) in E. coli. The potential of recombinant ISG65 (rISG65) as a diagnostic antigen was investigated in immunoblot and indirect ELISA using experimentally infected equine serum samples from 0 to 84 days post infection. The results indicated that rISG65 reacted with horse T. evansi positive serum giving two bands of approximately 48 kDa and 96 kDa. T. evansi-specific antibodies were detected as early as 10 and 14 days post infection using immunoblot and indirect ELISA, respectively using rISG65 antigen. No cross-reactivity was observed in ELISA and immunoblot with different serum samples of equines positive for Equine herpesvirus 1, Burkholderia mallei, and Theileria equi infections. Several immunoreactive regions were observed between 30 and 100 kDa in T. evansi isolate of horse origin indicating the existence of multiple copies of ISG protein in a single trypanosome. The recombinant ISG has proven to be good candidate antigen to be used in ELISA for serodiagnosis of T. evansi infection in different animals., Competing Interests: Competing interests The authors declare that they have no competing interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The discharge of untreated wastewater as a result of various developmental activities such as urbanization, industrialization and changes in lifestyle poses great threats to aquatic ecosystems as well as humans. Currently, ∼380 billion m 3 (380 trillion liters) of wastewater is generated globally every year. Around 70% of freshwater withdrawals are used for agricultural production throughout the world. The wastewater generated through agricultural run-off further pollutes freshwater resources. However, only 24% of the total wastewater generated from households and industries is treated before its disposal in rivers or reused in agriculture. The most problematic contaminants associated with ecological toxicity are heavy metals such as Cd, Cr, Cu, Ni, Zn, Fe, Pb, Hg, As and Mn. One of the most important issues linked with wastewater generation is the residual presence of pathogenic microorganisms which pose potential health hazards to consumers when they enter into the food chain. It is estimated that in India almost USD 600 million (48.60 billion INR) is spent per year to tackle waterborne diseases (WBD). In light of this, immediate action is needed to effectively treat wastewater and develop safer reuse prospects. Various wastewater treatment technologies have been established and they work well to provide an alternative water source to meet the growing demand. The main concern towards treating wastewater is to eliminate inorganic and organic substances and lower the nutrient concentration, total solids, and microbial pathogens to prevent freshwater pollution and health risks., 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 © 2022 Elsevier Ltd. All rights reserved.)

Autism spectrum disorder (ASD) is considered a complicated neurodevelopment disorder with rising prevalence globally. ASD is characterized by a series of events including varying degrees of defects in communication, learning, and social interaction which is accompanied by stereotypical behavioral patterns. Despite extensive research, the current diagnosis for ASD is complex and almost solely based on the behavioral assessments of the suspected individuals. The multifactorial etiopathology of this disease along with the diversity of symptoms among different individuals adds to the current intricacies for accurate prognosis of ASD. Hence, there exists a dire need for biologically relevant biomarkers for an early diagnosis and for tracking the efficacy of therapeutic interventions. Until recently, among various biofluids, saliva has gained increasing interest for biomarker identification, the advantages include the non-invasive nature and ease of sample handling. This mini-review aims to provide a succinct summary of recent literature on saliva-based diagnostic modalities for ASD, examine various studies that highlight the potential use of proteomic and/or RNA-based biomarkers. Finally, some conclusive perspectives of using the salivary system for ASD mechanistic details and diagnosis are also discussed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sharma, Choudhury, Kumar and Nikolajeff.)

The continuous exposure to pharmaceuticals and personal care products can lead to a series of individual antagonistic and synergistic effects and long-lasting toxicity to humans and aquatic lives. This may also lead to developing antibiotic resistance, teratogenic, carcinogenic, and endocrine-disrupting effects. However, several PPCPs are also considered biologically active for non-target aquatic organisms, such as mosquito fish, goldfish, and the algae Pseudokirchneriella subcapitata. Various physicochemical methods such as ozonation, photolysis, and membrane separation are recognized for the effective removal of PPCPs. However, the high operation and maintenance costs and associated ecological impacts have limited their further use. Constructed wetlands are considered eco-friendly and sustainable for the removal of pharmaceuticals and personal care products together with antibiotic resistance genes. Several mechanisms such as sorption, biodegradation, oxidation, photodegradation, volatilization, and hydrolysis are occurring during the phytoremediation of PPCPs. During these processes, more than 50% of PPCPs can be eliminated through constructed wetlands. They also offer several additional benefits as obtained macrophytic biomass may be used as raw material in pulp and paper industries and a source for second-generation biofuel production. In this study, we have discussed the origin and impacts of PPCPs together with their treatment methods. We have also investigated the strengths, weaknesses, opportunities, and threats associated with constructed wetlands during the treatment of wastewater laden with pharmaceutical and personal care products., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Serodiagnosis of surra, caused by Trypanosoma evansi, is still based on native antigens purified from bloodstream form of T. evansi grown in rodents. In order to investigate prospective diagnostic possibilities as an alternative for native antigens, we cloned, expressed 26 kDa calflagin protein containing 218 amino acids from T. evansi (Indian Strain) in Escherichia coli. The potential of recombinant calflagin (rCLF) protein as diagnostic antigen was evaluated in immunoblot and indirect ELISA using experimentally infected equine serum samples from 0 to 84 days post infection. The antibodies against T. evansi were detected with rCLF antigen in serum samples of experimentally infected equines as early as 10 days and 14 days post infection, using immunoblot and ELISA respectively. No cross-reactivity was observed with rCLF antigen in ELISA with different serum samples of equines positive for Equine herpesvirus 1, Burkholderia mallei, and Theileria equi infections. Several immunoreactive regions ranging from 10 to 28 kDa were detected using distinct T. evansi isolates (pony, cattle, donkey and camel origin) indicating presence of multiple calflagin family members in a single trypanosome. Indirect immunofluorescence antibody test with anti-CLF rabbit hyperimmune serum showed localisation of native immunogenic protein near attachment of flagellum. The rCLF protein was found to be a potential diagnostic candidate for distinguishing T. evansi positive and negative equine serum sample, suggesting that it could be used for serological surveys in animals for surra. In addition, it could be used with other potential diagnostic candidates to improve the diagnostic efficiency., Competing Interests: Conflict of interest statement The corresponding author on behalf of all authors of the manuscript declare that they have no competing interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)

A person suspected of having Alzheimer's disease (AD) is clinically diagnosed for the presence of principal biomarkers, especially misfolded amyloid-beta (Aβ) and tau proteins in the brain regions. Existing radiotracer diagnostic tools, such as PET imaging, are expensive and have limited availability for primary patient screening and pre-clinical animal studies. To change the status quo, small-molecular near-infrared (NIR) probes have been rapidly developed, which may serve as an inexpensive, handy imaging tool to comprehend the dynamics of pathogenic progression in AD and assess therapeutic efficacy in vivo . This Perspective summarizes the biochemistry of Aβ and tau proteins and then focuses on structurally diverse NIR probes with coverages of their spectroscopic properties, binding affinity toward Aβ and tau species, and theranostic effectiveness. With the summarized information and perspective discussions, we hope that this paper may serve as a guiding tool for designing novel in vivo imaging fluoroprobes with theranostic capabilities in the future.

Introduction: Enzyme-linked immunosorbent assay (ELISA) is a key bio-analytical technique used for the detection of a large array of antigenic substances of scientific, clinical, food safety, and environmental importance. The assay primarily involves capturing and detecting target analytes using specific antigen-antibody interactions. The wide usage of ELISA results from its high specificity and reproducibility. Notwithstanding, the conventional microwell plate-based format of ELISA has some major drawbacks, such as long assay time (4-18 h), large sample volumes requirement (100-200 μL), lack of multiplicity, and burdensome procedures that limit its utility in rapid and affordable diagnostics., Areas Covered: Here, we reviewed microfluidic-ELISA, paper-ELISA, aptamer-ELISA, and those based on novel incubation such as heat-ELISA, pressure-ELISA, microwave-ELISA, and sound-ELISA. Further, the current trends and future prospects of these ELISA protocols in clinical diagnostics are discussed., Expert Opinion: The reviewed non-conventional ELISA formats are relatively rapid, require low reagent volumes, are multiplexable, and could be performed in a low-cost setup. In our opinion, these non-conventional variants of ELISA are on a par with the conventional format for clinical diagnostics and fundamental biological research and hold added clinical translational potential for quick, inexpensive, and convenient measurements.

Parkinson's disease (PD) is a neurological disorder that affects the movement of the human body. It is primarily characterized by reduced dopamine levels in the brain. The causative agent of PD is still unclear but it is generally accepted that α-synuclein has a central role to play. It is also known that gap-junctions and associated connexins are complicated structures that play critical roles in nervous system signaling and associated misfunctioning. Thus, our current article emphasizes how, alongside α-synuclein, ion-channels, gap-junctions, and related connexins, all play vital roles in influencing multiple metabolic activities of the brain during PD. It also highlights that ion-channel and gap-junction disruptions, which are primarily mediated by their structural-functional changes and alterations, have a role in PD. Furthermore, we discussed available drugs and advanced therapeutic interventions that target Parkinson's pathogenesis. In conclusion, it warrants creating better treatments for PD patients. Although, dopaminergic replenishment therapy is useful in treating neurological problems, such therapies are, however, unable to control the degeneration that underpins the disease, thereby declining their overall efficacy. This creates an additional challenge and an untapped scope for neurologists to adopt treatments for PD by targeting the ion-channels and gap-junctions, which is well-reviewed in the present article., (© 2022. The Author(s).)

The pandemic caused by SARS-CoV-2 (SCoV-2) has impacted the world in many ways and the virus continues to evolve and produce novel variants with the ability to cause frequent global outbreaks. Although the advent of the vaccines abated the global burden, they were not effective against all the variants of SCoV-2. This trend warrants shifting the focus on the development of small molecules targeting the crucial proteins of the viral replication machinery as effective therapeutic solutions. The PLpro is a crucial enzyme having multiple roles during the viral life cycle and is a well-established drug target. In this study, we identified 12 potential inhibitors of PLpro through virtual screening of the FDA-approved drug library. Docking and molecular dynamics simulation studies suggested that these molecules bind to the PLpro through multiple interactions. Further, IC 50 values obtained from enzyme-inhibition assays affirm the stronger affinities of the identified molecules for the PLpro. Also, we demonstrated high structural conservation in the catalytic site of PLpro between SCoV-2 and Human Coronavirus 229E (HCoV-229E) through molecular modelling studies. Based on these similarities in PLpro structures and the resemblance in various signalling pathways for the two viruses, we propose that HCoV-229E is a suitable surrogate for SCoV-2 in drug-discovery studies. Validating our hypothesis, Mefloquine, which was effective against HCoV-229E, was found to be effective against SCoV-2 as well in cell-based assays. Overall, the present study demonstrated Mefloquine as a potential inhibitor of SCoV-2 PLpro and its antiviral activity against SCoV-2. Corroborating our findings, based on the in vitro virus inhibition assays, a recent study reported a prophylactic role for Mefloquine against SCoV-2. Accordingly, Mefloquine may further be investigated for its potential as a drug candidate for the treatment of COVID., Competing Interests: MA and SKa were commercial employed by Srikara Biologicals Private Limited, Tirupati. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest., (Copyright © 2022 Kulandaisamy, Kushwaha, Dalal, Kumar, Singh, Baswal, Sharma, Praneeth, Jorwal, Kayampeta, Sharma, Maddur, Kumar, Kumar, Polamarasetty, Singh, Sehgal, Gholap, Appaiahgari, Katika and Inampudi.)

Purpose: To compare osteocalcin and crestal bone loss in implants placed under an immediate loading (IL) compared to a delayed loading (DL) protocol., Materials and Methods: This preliminary, split-mouth, randomized controlled trial included 14 participants who required replacement of both mandibular first molars opposing a completely dentate maxillary arch. Two implants were placed in each participant. According to the split-mouth randomization method, a temporary crown was used for the IL protocol and a healing abutment was used for the DL protocol in each participant. Definitive crowns were cemented 3 months after implant placement. Osteocalcin levels were determined using ELISA, and crestal bone loss was evaluated using radiographs at 2 weeks, 3 months, and 12 months after implant placement., Results: The mean osteocalcin level was significantly higher with IL than DL at each point (P < .001), with 95% CI of -262.89 to -439.10 (2 weeks); -238.02 to -375.98 (3 months); and -83.24 to -211.61 (12 months). Higher crestal bone loss was observed in IL when compared to DL implants at 2 weeks (P = .458, 95% CI: -0.10 to 0.21). Less crestal bone loss was observed with IL than DL at 3 months (P = .935) and 12 months (P = .42)., Conclusion: Osteocalcin levels increased in both IL and DL implants, but higher levels were observed with IL. Higher crestal bone loss was observed with IL during the initial stages of treatment only.

Kidney Disease Improving Global Outcomes (KDIGO) 2017 Clinical Practice Guideline has recommended treatment decisions for patients with chronic kidney disease (CKD) with osteoporosis and/or high risk of fracture. Bisphosphonates, the first-line anti-osteoporosis drugs have the concern of worsening kidney functions. Moreover, despite impaired bone formation in CKD patients, teriparatide, the formation-stimulating drug is not recommended. Thus, there is an urgent need for safe and effective treatment of osteoporosis in CKD patients. Here, in CKD rats, we tested the osteoprotective effect of diosmin, a citrus-derived bioflavonoid used as a phlebotonic in chronic venous insufficiency and has a renoprotective effect. CKD was developed by 5/6 th nephrectomy and diosmin at the human equivalent dose (100 mg kg -1 ) did not advance renal failure but reduced blood pressure to the level of sham control. Fibroblast growth factor-23 and parathyroid hormone were increased in CKD and diosmin suppressed both. CKD reduced bone mass and deteriorated the microarchitecture of trabecular bones, and diosmin maintained both to control levels. Bone formation and strength were impaired in the CKD and diosmin maintained these levels to control levels. Nanoindentation of bone showed that diosmin significantly increased tissue hardness over the control. Diosmetin, the metabolic surrogate of diosmin had comparable pharmacokinetic profiles between the control and CKD groups. Furthermore, diosmetin (50 mg kg -1 ) protected against CKD-induced bone loss. These data suggest that diosmin and its metabolic surrogate, diosmetin protect against CKD-induced osteopenia. Since diosmin has no renal adverse effect and protected bone mass and strength in CKD rats, we propose assessing its anti-osteoporosis effect in CKD patients.

The pathological hallmarks of Alzheimer's disease (AD) are manifested as an increase in the level of oxidative stress and aggregation of the amyloid-β protein. In vitro , in vivo , and in silico experiments were designed and carried out with multifunctional cholinergic inhibitor, F24 (EJMC- 7a ) to explore its neuroprotective effects in AD models. The neuroprotection ability of F24 was tested in SH-SY5Y cells, a widely used neuronal cell line. The pretreatment and subsequent co-treatment of SH-SY5Y cells with different doses of F24 was effective in rescuing the cells from H 2 O 2 induced neurotoxicity. F24 treated cells were found to be effective in the reduction of cellular reactive oxygen species, DNA damage, and Aβ 1-42 induced neurotoxicity, which validated its neuroprotective effectiveness. F24 exhibited efficacy in an in vivo Drosophila model by rescuing eye phenotypes from degeneration caused by Aβ toxicity. Further, computational studies were carried out to monitor the interaction between F24 and Aβ 1-42 aggregates. The computational studies corroborated our in vitro and in vivo studies suggesting Aβ 1-42 aggregation modulation ability of F24. The brain entry ability of F24 was studied in the parallel artificial membrane permeability assay. Finally, F24 was tested at doses of 1 and 2.5 mg/kg in the Morris water maze AD model. The neuroprotective properties shown by F24 strongly suggest that multifunctional features of this molecule provide symptomatic relief and act as a disease-modifying agent in the treatment of AD. The results from our experiments strongly indicated that natural template-based F24 could serve as a lead molecule for further investigation to explore multifunctional therapeutic agents for AD management.

Eight free water surface constructed wetland microcosm (CWM) units are designed with single as well as mixed planting of Pistia stratiotes, Phragmites karka, and Typha latifolia with control to assess their competitive value (CV), relative growth rates (RGR), and pollutants removal efficiency. Further, the total dry biomass production and other growth parameters such as number of macrophytes, above-ground biomass, below-ground biomass, and root length were also measured to understand the dominant characteristics of the macrophytes. The CWM units with species mixture out-performed species monocultures. Removal of BOD, TP, SRP, NH 4 + -N, NO 3 - -N, and NO 2 - -N by mixed planting of P. stratiotes and P. karka was higher at most of the time. Typha latifolia was the superior competitor against both P. stratiotes and P. karka due to its aggressive characteristics that inhibits the growth of neighboring macrophytes. However, P. karka was the superior competitor against P. stratiotes. The RGR of T. latifolia in all experimental units was almost two times more than that of P. karka. Novelty Statement The CWM units with species mixture out-performed species monocultures. CWMs with more than one macrophytic species are less vulnerable to seasonal fluctuations and more effective in contaminants removal as compared to single macrophyte wetlands. Removal of BOD, TP, SRP, NH 4 + -N, NO 3 - -N, and NO 2 - -N by mixed planting of P. stratiotes and P. karka was higher at most of the time. The CWMs with P. stratiotes and P. karka are superior choice due to their higher wastewater nutrients removal capacity. The application of these three macrophytes in mixed cultures in free water surface constructed wetland is rare. The results are useful in designing large-scale multi-species wetlands which are less susceptible to seasonal variation and more effective in pollutants removal than single-species wetlands.

As imaging technology plays an important role in the diagnosis and evaluation of the new coronavirus pneumonia (COVID-19), COVID-19 related data sets have been published one after another, but there are relatively few data sets and research progress in related literature. To this end, through COVID-19-related journal papers, reports, and related open-source data set websites, organize and analyze the new coronary pneumonia data set and the deep learning models involved, including computed tomography (CT) image data sets and X-ray (CXR) Image dataset. Analyze the characteristics of the medical images presented in these data sets; focus on open-source data sets, as well as classification and segmentation models that perform well on related data sets. Finally, the future development trend of lung imaging technology is discussed., Competing Interests: 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 © 2022 Elsevier Ltd. All rights reserved. Selection and peer-review under responsibility of the scientific committee of the International Conference on Innovative Technology for Sustainable Development.)

The elusiveness encircling around the domain of cognition, its impairment, and the poor prognosis of Alzheimer's disease has made early diagnosis a necessity. The noticeable symptoms in these conditions appear years later after the neuropathological changes occur in the brain. Exosomes, a small-sized extracellular vesicle facilitate intercellular communication of disease pathologies and their cargo can provide molecular information about its place of origin. The study titled "A novel approach to correlate the salivary exosomes and their protein cargo in the progression of cognitive impairment into Alzheimer's disease" was an attempt toward understanding the role of salivary small-sized extracellular vesicular (EV's) cargo in monitoring the progression. Outcomes of the study represent, that the salivary small-sized EV's (ssEV's) levels were higher in the cognitively impaired and Alzheimer's diseased as well the differential expression of the protein in the cargo correlates well with the disease severity staging. Thus, it can help in the development of an early non-invasive screening method., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Coronavirus disease 2019 (COVID-19) is a life-threatening respiratory infection caused by severe acute respiratory syndrome virus (SARS-CoV-2), a novel human coronavirus. COVID-19 was declared a pandemic by World Health Organization in March 2020 for its continuous and rapid spread worldwide. Rapidly emerging COVID-19 epicenters and mutants of concerns have created mammoth chaos in healthcare sectors across the globe. With over 185 million infections and approximately 4 million deaths globally, COVID-19 continues its unchecked spread despite all mitigation measures. Until effective and affordable antiretroviral drugs are made available and the population at large is vaccinated, timely diagnosis of the infection and adoption of COVID-appropriate behavior remains major tool available to curtail the still escalating COVID-19 pandemic. This review provides an updated overview of various techniques of COVID-19 testing in human samples and also discusses, in brief, the biochemical composition and mode of transmission of the SARS-CoV-2. Technological advancement in various molecular, serological and immunological techniques including mainly the reverse-transcription polymerase chain reaction (RT-PCR), CRISPR, lateral flow assays (LFAs), and immunosensors are reviewed., (© 2021 The Author(s).)

Introduction: Accurate determination of the aberrantly expressed biomarkers such as human epidermal growth factor receptor 2 (HER2), carcinoembryonic antigen (CEA), platelet-derived growth factor (PDGF), mucin 1 (MUC1), and vascular endothelial growth factor VEGF 165 have played an essential role in the clinical management of the breast cancer. Assessment of these cancer-specific biomarkers has conventionally relied on time-taking methods like the enzyme-linked immunosorbent assay and immunohistochemistry. However, recent development in the aptamer-based diagnostics has allowed developing tools that may substitute the conventional means of biomarker assessment in breast cancer. Adopting the aptamer-based diagnostic tools (aptasensors) to clinical practices will depend on their analytical performance on clinical samples., Areas Covered: In this review, we provide an overview of the analytical merits of HER2, CEA, PDGF, MUC1, and VEGF 165 aptasensors. Scopus and Pubmed databases were searched for studies reporting aptasensor development for the listed breast cancer biomarkers in the past one decade. Linearity, detection limit, and response time are emphasized., Expert Opinion: In our opinion, aptasensors have proven to be on a par with the antibody-based methods for detection of various breast cancer biomarkers. Though robust validation of the aptasensors on significant sample size is required, their ability to detect pathophysiological range of biomarkers suggest the possibility of future clinical adoption.

Alzheimer's disease (AD) is an age-related multifactorial neurodegenerative disorder characterized by severe central cholinergic neuronal loss, gradually contributing to cognitive dysfunction and impaired motor activity, resulting in the brain's cell death at the later stages of AD. Although the etiology of AD is not well understood, however, several factors such as oxidative stress, deposition of amyloid-β (Aβ) peptides to form Aβ plaques, intraneuronal accumulation of hyperphosphorylated tau protein, and low level of acetylcholine are thought to play a major role in the pathogenesis of AD. There is practically no drug for AD treatment that can address the basic factors responsible for the neurodegeneration and slow down the disease progression. The currently available therapies for AD in the market focus on providing only symptomatic relief without addressing the aforesaid basic factors responsible for the neurodegeneration. Ferulic acid (FA) is a phenol derivative from natural sources and serves as a potential pharmacophore that exerts multiple pharmacological properties such as antioxidant, neuroprotection, Aβ aggregation modulation, and anti-inflammatory. Several FA based hybrid analogs are under investigation as a multi-target directed ligand (MTDLs) to develop novel hybrid compounds for the treatment of AD. In the present review article, we are focused on the critical pathogenic factors responsible for the onset of AD followed by the developments of FA pharmacophore-based hybrids compounds as a novel multifunctional therapeutic agent to address the limitations associated with available treatment for AD. The rationale behind the development of these compounds and their pharmacological activities in particular to their ChE inhibition (ChEI), neuroprotection, antioxidant property, Aβ aggregation modulation, and metal chelation ability, are discussed in detail. We have also discussed the discovery of caffeic and cinnamic acids based MTDLs for AD. This review paper provides an in-depth insight into the research progress and current status of these novel therapeutics in AD and prospects for developing a druggable molecule with desired pharmacological affinity and reduced toxicity for the management of AD., 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 © 2021 Elsevier Masson SAS. All rights reserved.)

Background: The p53, tumor suppressor protein is inactivated upon mutation in the DNA-binding domain and the non-functional protein leads to cancers. The p53Y220C is one of the most frequently observed mutations in p53 with a scope of rescuing the protein function using small molecules., Methods: Using computational modeling, biophysical, and experimental cell-based studies we tried to understand the molecular basis of Curcumin as a potential small molecule to stabilize p53Y220C mutant and restore its function. The pancreatic adenocarcinomas BxPC-3 p53Y220C mutant cell line was used for cell-based assays to determine the therapeutic potential of Curcumin to restore mutant p53 to function like wild type., Results: Our results showed that the Curcumin binds p53Y220C with K d  = 3.169 ± 0.257 μM and it increases the DNA binding affinity of the mutant by 4-fold with K d  = 851.29 ± 186.27 nM. By Fluorescence, CD, and IR spectroscopy, we could characterize the secondary structural changes and stabilization of the p53Y220C DNA binding domain upon Curcumin binding. By caspase-3 and Annexin V assays, we could demonstrate that Curcumin at 3 μM to 8 μM concentration could initiate p53 mediated apoptosis in BxPC-3 cell line. Based on our experimental studies, we propose a mechanism for the activation of ATM/Chk1 kinases pathways for apoptosis and/or G2/M cell cycle arrest in the BxPC-3 cell line mediated by functionally restored p53Y220C., Conclusion: The study indicated that the natural compound Curcumin could rescue mutant p53Y220C in BxPC-3 pancreatic adenocarcinomas cell line to function like wild-type and activate apoptotic pathways., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Biomineralization can be considered as nature's strategy to produce and sustain biominerals, primarily via creation of hard tissues for protection and support. This review examines the biomineralization process within the hard tissues of the human body with special emphasis on the mechanisms and principles of bone and teeth mineralization. We describe the detailed role of proteins and inorganic ions in mediating the mineralization process. Furthermore, we highlight the various available models for studying bone physiology and mineralization starting from the historical static cell line-based methods to the most advanced 3D culture systems, elucidating the pros and cons of each one of these methods. With respect to the mineralization process in teeth, enamel and dentin mineralization is discussed in detail. The key role of intrinsically disordered proteins in modulating the process of mineralization in enamel and dentine is given attention. Finally, nanotechnological interventions in the area of bone and teeth mineralization, diseases and tissue regeneration is also discussed. STATEMENT OF SIGNIFICANCE: This article provides an overview of the biomineralization process within hard tissues of the human body, which encompasses the detailed mechanism innvolved in the formation of structures like teeth and bone. Moreover, we have discussed various available models used for studying biomineralization and also explored the nanotechnological applications in the field of bone regeneration and dentistry., (Copyright © 2020 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Neurodegenerative diseases (ND) remains to be one of the biggest burdens on healthcare systems and serves as a leading cause of disability and death. Alzheimer's disease (AD) is among the most common of such disorders, followed by Parkinson's disease (PD). The basic molecular details of disease initiation and pathology are still under research. Only recently, the role of exosomes has been linked to the initiation and progression of these neurodegenerative diseases. Exosomes are small bilipid layer enclosed extracellular vesicles, which were once considered as a cellular waste and functionless. These nano-vesicles of 30-150 nm in diameter carry specific proteins, lipids, functional mRNAs, and high amounts of non-coding RNAs (miRNAs, lncRNAs, and circRNAs). As the exosomes content is known to vary as per their originating and recipient cells, these vesicles can be utilized as a diagnostic biomarker for early disease detection. Here we review exosomes, their biogenesis, composition, and role in neurodegenerative diseases. We have also provided details for their characterization through an array of available techniques. Their updated role in neurodegenerative disease pathology is also discussed. Finally, we have shed light on a novel field of salivary exosomes as a potential candidate for early diagnosis in neurodegenerative diseases and compared the biomarkers of salivary exosomes with other blood/cerebrospinal fluid (CSF) based exosomes within these neurological ailments., Competing Interests: The authors declare no conflict of interest.

There was a significant decline in air pollution in different parts of the world due to enforcement of lockdown by many countries to check the spread of the coronavirus (COVID-19) pandemic. In particular, commercial and industrial activities had been limited globally with restricted air and surface traffic movements in response to social distancing and isolation. Both satellite remote sensing and ground-based monitoring were used to measure the change in the air quality. There was momentous decline in the averaged concentrations of nitrogen dioxide (NO 2 ), carbon dioxide (CO 2 ), sulphur dioxide (SO 2 ), methane (CH 4 ) and aerosols. Many cities across India, China and several major cities in Europe observed strong reductions in nitrogen dioxide levels dropping by around 40-50% owing to lockdowns. Similarly, concentrations of SO 2 in polluted areas in India, especially around large coal-fired power plants and industrial areas decreased by around 40% as evidenced by the comparative satellite mapping during April 2019 and April 2020. Recent advances in sensors on board various satellites played a significant role in real-time monitoring of emission regimes over various parts of the world. The satellite data is relying upon single scene profusion for real-time air quality measurements, and also using averaged dataset over certain time-period. The daily global-scale remote sensing data of NO 2 , as measured through the Copernicus Sentinel-5 Precursor Tropospheric Monitoring Instrument (S5p/TROPOMI) of European Space Agency (ESA), indicated exceptional decreases in tropospheric NO 2  pollution in urban areas. Similarly, Greenhouse gases Observing Satellite (GOSAT) of Japan Aerospace Exploration Agency, with a repeat cycle of three days helped in assessing the sources and sinks of CO 2 and CH 4 on a sub-continental scale., Supplementary Information: The online version contains supplementary material available at 10.1007/s42398-021-00166-w., Competing Interests: Conflict of interestThe authors declare no conflict of interest., (© Society for Environmental Sustainability 2021.)