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The effects of polyphenols from Tasmanian pepper (Tasmannia Lanceolata) leaf and berry on the functional properties of pea protein were investigated in flaxseed oil-in-water emulsions. Phenolic acids and flavonols in Tasmanian pepper leaf with smaller molecular weights led to stronger non-covalent interactions with pea protein, while anthocyanins from Tasmanian pepper berry induced protein aggregation under acidic condition and co-existed with proteins in neutral and alkaline conditions. The total phenolic content was significantly increased with incorporation of polyphenols from Tasmanian pepper leaf (334.94-445.92 μg/mL) and berry (72.89-153.03 μg/mL) to pea protein (4.19-15.59 μg/mL). The oxidative stability of emulsions at pH 3 and 7 was enhanced, reducing TBARS value from 1.54 to 2.68 mg MDA/kg in pea protein to 0.56-0.85 mg MDA/kg after 2 weeks storage. These findings illustrated the distinct interactions between pea protein and different polyphenols from Tasmanian pepper leaf and berry to enhance the antioxidant capacity of pea protein., 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. Printed version of figures in black-and-white. No color in print is required., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Ionic liquids (ILs) represent an exciting and promising solution for advancing drug delivery platforms. Their unique properties, including broad chemical diversity, adaptable structures, and exceptional thermal stability, make them ideal candidates for overcoming challenges in transdermal drug delivery. Despite encountering obstacles such as side reactions, impurity effects, biocompatibility concerns, and stability issues, ILs offer substantial potential in enhancing drug solubility, navigating physiological barriers, and improving particle stability. To propel the use of IL-based drug delivery in pharmaceutical innovation, it is imperative to devise new strategies and solvents that can amplify drug effectiveness, facilitate drug delivery to cells at the molecular level, and ensure compatibility with the human body. This review introduces innovative methods to effectively address the challenges associated with transdermal drug delivery, presenting progressive approaches to significantly improve the efficacy of this drug delivery system., 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 © 2024 Jain, Shakya, Prajapati, Eldesoqui, Mody, Jain, Naik and Patil.)

Purpose: The reliable estimation of the vertebral body posture helps to aid a safe and effective spine surgery. The proposed work aims to present an MR to X-ray image registration to assess the 3D pose of the vertebral body during spine surgery. The 3D assessment of vertebral pose assists in analyzing the position and orientation of the vertebral body to provide information during various clinical diagnosis conditions such as curvature estimation and pedicle screw insertion surgery., Methods: The proposed feature-based registration framework extracted vertebral end plates to avoid the mismatch between the intensities of MR and X-ray images. Using the projection matrix, the segmented MRI is forward projected and then registered to the X-ray image using binary image matching similarity and the CMA-ES optimizer., Results: The proposed method estimated the vertebral pose by registering the simulated X-ray onto pre-operative MRI. To evaluate the efficacy of the proposed approach, a certain number of experiments are carried out on the simulated dataset., Conclusion: The proposed method is a fast and accurate registration method that can provide 3D information about the vertebral body. This 3D information is useful to improve accuracy during various clinical diagnoses., (© 2023. The Author(s).)

Sitophilus oryzae is a kind of stored grain pest. This is controlled by using natural pesticides, which are more reliable, cost-effective, biodegradable, and eco-friendly than synthetic pesticides. Several plants show different insecticidal activities against various pests on their different parts (leaves, seeds, etc.). In this study, methanolic extracts of Lantana camara (leaves), Carica papaya (seeds), Ricinus communis (leaves), Calotropis gigantea (flowers), and Gliciridia sepium (leaves) were used to identify the best insecticidal activity against the rice weevil by doing mortality tests for one week with four replications under laboratory conditions. Gliciridia sepium leaves showed the highest insecticidal activity (100 ± 0) after seven days, and its extract was fractionated by using column chromatography and yielded 12 fractions. A contact bioassay of each fraction was performed, and fraction-11 showed the highest insecticidal activity against Sitophilus oryzae with a 100 % mortality after four days. Fraction-11 was analyzed by using GC-MS and FT-IR. Results revealed that the major constituent identified in fraction-11 was 4-C-methyl-myo-inositol. Therefore, 4-C-methyl-myo-inositol acts as a natural insecticide against rice weevils., 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.)

Plant-based proteins, represented by amaranth in our study, embrace a potential as an ingredient for the functional-food formulation. However, their efficacy is hindered by inherent limitations in solubility, emulsification, and antioxidant traits. The Maillard reaction, a complex chemical-process resulting in a diverse array of products, including Maillard conjugates and Maillard reaction products (MRPs), can employ variable effects on these specific attributes. To elucidate the influence of this reaction and the MRPs on the aforementioned properties, we used a complex blend of dehydrated seaweed Gracilaria and amaranth protein to create a conjugate-MRP blend. Our investigations revealed that the resultant incorporation enhanced solubility, emulsification, and antioxidant properties, while the intermediates formed did not progress to advanced glycation stages. This change is likely attributed to the dual effect of conjugates that altered the secondary protein structure, while the generation and/or preservation of MRPs post ultrasonication and spray drying enhanced its antioxidant potential., 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 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

High-grade serous ovarian carcinoma (HGSC) is associated with late-stage disease presentation and poor prognosis, with a limited understanding of early transformation events. Our study analyzes HGSC tumor progression and organ-specific metastatic dissemination to identify hypoxia-associated molecular, cellular, and histological alterations. Clinical characteristics of the HGSC were replicated in orthotopic xenografts, which involve metastatic dissemination and the prevalence of group B tumors (volume: >0.0625 ≤ 0.5 cm3). Enhanced hyaluronic acid (HA) deposition, expanded tumor vasculature, and increased necrosis contributed to the remodeling of tumor tissue architecture. The proliferative potential of tumor cells and the ability to form glands were also altered during tumor growth. Flow cytometry and label chase-based molecular profiling across the tumor regenerative hierarchy identified the hypoxia-vasculogenic niche and the hybrid epithelial-mesenchymal tumor-cell state as determinants of self-renewal capabilities of progenitors and cancer stem cells. A regulatory network and mathematical model based on tumor histology and molecular signatures predicted hypoxia-inducible factor 1-alpha (HIF1A) as a central node connecting HA synthesis, epithelial-mesenchymal transition, metabolic, vasculogenic, inflammatory, and necrotic pathways in HGSC tumors. Thus, our findings provide a temporal resolution of hypoxia-associated events that sculpt HGSC tumor growth; an in-depth understanding of it may aid in the early detection and treatment of HGSC., (© 2022 S. Karger AG, Basel.)

Nanotechnology is one of the most appealing area for developing new applications in biotechnology and medicine. For decades, nanoparticles have been extensively studied for a variety of biomedical applications. Silver has evolved into a potent antibacterial agent that can be used in a variety of nanostructured materials of various shapes and sizes. Silver nanoparticles (AgNP) based antimicrobial compounds are employed in a wide range of applications, including medicinal uses, surface treatment and coatings, the chemical and food industries, and agricultural productivity. When designing formulations for specific applications, the size, shape, and surface area of AgNPs are all crucial structural aspects to consider. Different methods for producing AgNPs with varying sizes and forms that are less harmful have been devised. The anticancer, anti-inflammatory, antibacterial, antiviral, and anti-angiogenic properties of AgNPs have been addressed in this review, as well as their generation and processes. Herein, we have reviewed the advances in therapeutic applications of AgNPs, as well as their limitations and barriers for future 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 B.V. All rights reserved.)

The rise in the resistance to antibiotics is due to their inappropriate use and the use of a broad spectrum of antibiotics. This has also contributed to the development of multidrug-resistant microorganisms, and due to the unavailability of suitable new drugs for treatments, it is difficult to control. Hence, there is a need for the development of new novel, target-specific antimicrobials. Nanotechnology, involving the synthesis of nanoparticles, may be one of the best options, as it can be manipulated by using physicochemical properties to develop intelligent NPs with desired properties. NPs, because of their unique properties, can deliver drugs to specific targets and release them in a sustained fashion. The chance of developing resistance is very low. Polymeric nanoparticles are solid colloids synthesized using either natural or synthetic polymers. These polymers are used as carriers of drugs to deliver them to the targets. NPs, synthesized using poly-lactic acid (PLA) or the copolymer of lactic and glycolic acid (PLGA), are used in the delivery of controlled drug release, as they are biodegradable, biocompatible and have been approved by the USFDA. In this article, we will be reviewing the synthesis of PLGA-based nanoparticles encapsulated or loaded with antibiotics, natural products, or metal ions and their antibacterial potential in various medical applications.

Hematopoietic cell transplantation (HCT) impacts recipients' quality of life (QoL). Few mindfulness-based interventions (MBI) in HCT recipients have shown feasibility, but heterogeneous practices and outcome measures have called into question the actual benefit. We hypothesized that self-guided isha kriya, a 12-minute guided meditation based on the principles of yoga focusing on breathing, awareness, and thought, as a mobile app would improve QoL in the acute HCT setting. This single-center, open-label, randomized controlled trial was conducted in 2021 to 2022. Autologous and allogeneic HCT recipients age ≥18 years were included. The study was approved by our Institutional Ethics Committee and registered at the Clinical Trial Registry of India, and all participants provided written informed consent. HCT recipients without access to smartphones or regular practitioners of yoga, meditation, or other mind-body practices were excluded. Participants were randomized to the control arm or the isha kriya arm at a 1:1 ratio stratified by type of transplantation. Patients in the isha kriya arm were instructed to perform the kriya twice daily from pre-HCT to day +30 post-HCT. The primary endpoint was QoL summary scores as assessed by the Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) and the Patient-Reported Outcomes Measurement Information System Global Health (PROMIS-GH) questionnaires. The secondary endpoints were the differences in QoL domain scores. The validated questionnaires were self-administered before the intervention and at days +30 and +100 post-HCT. The analysis of endpoints was done on an intention-to-treat basis. Domain and summary scores were calculated for each instrument as recommended by the developers. A P value < .05 was considered to indicate statistical significance, and Cohen's d effect size was used to determine clinical significance. A total of 72 HCT recipients were randomized to the isha kriya and control arms. Patients in the 2 arms were matched for age, sex, diagnosis, and type of HCT. The 2 arms showed no differences in pre-HCT QoL domain, summary, and global scores. At day +30 post-HCT, there was no difference between the arms in the mean FACT-BMT total score (112.9 ± 16.8 for the isha kriya arm versus 101.2 ± 13.9 for the control arm; P = .2) or the mean global health score (global mental health, 45.1 ± 8.6 versus 42.5 ± 7.2 [P = .5]; global physical health, 44.1 ± 6.3 versus 44.1 ± 8.3 [P = .4]) in the 2 groups. Similarly, there were no differences in physical, social, emotional, and functional domain scores. However, the mean bone marrow transplantation (BMT) subscale scores, which addresses BMT-specific QoL concerns, were statistically and clinically significantly higher in the isha kriya arm (27.9 ± 5.1 versus 24.4 ± 9.2; P = .03; Cohen's d = .5; medium effect size). This effect was transient; mean day +100 scores showed no difference (28.3 ± 5.9 versus 26.2 ± 9.4; P = .3). Our data indicate that the isha kriya intervention did not improve the FACT-BMT total and global health scores in the acute HCT setting. However, practicing isha kriya for 1 month was associated with transient improvement in the FACT-BMT subscale scores on day +30 but not on day +100 post-HCT., (Copyright © 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

There has been a new approach in the development of antibacterials in order to enhance the antibacterial potential. The nanoparticles are tagged on to the surface of other metals or metal oxides and polymers to achieve nanocomposites. These have shown significant antibacterial properties when compared to nanoparticles. In this article we explore the antibacterial potentials of metal-based and metal-polymer-based nanocomposites, various techniques which are involved in the synthesis of the metal-polymer, nanocomposites, mechanisms of action, and their advantages, disadvantages, and applications.

Competing Interests: There are no conflicts of interest.

The use of the synthetic drugs has increased in the last few decades; however, these drugs exhibit various side effects. Scientists are therefore seeking alternatives from natural sources. Commiphora gileadensis has long been used to treat various disorders. It is commonly known as bisham or balm of Makkah. This plant contains various phytochemicals, including polyphenols and flavonoids, with biological potential. We found that steam-distilled essential oil of C. gileadensis exhibited higher antioxidant activity (IC 50, 22.2 µg/mL) than ascorbic acid (IC 50, 1.25 µg/mL). The major constituents (>2%) in the essential oil were β-myrcene, nonane, verticiol, β-phellandrene, β-cadinene, terpinen-4-ol, β-eudesmol, α-pinene, cis-β-copaene and verticillol, which might be responsible for the antioxidant and antimicrobial activity against Gram-positive bacteria. The extract of C. gileadensis exhibited inhibitory activity against cyclooxygenase (IC 50, 450.1 µg/mL), xanthine oxidase (251.2 µg/mL) and protein denaturation (110.5 µg/mL) compared to standard treatments, making it a viable treatment from a natural plant source. LC-MS analysis revealed the presence of phenolic compounds such as caffeic acid phenyl ester, hesperetin, hesperidin, chrysin and transient amounts of catechin, gallic acid, rutin and caffeic acid. The chemical constituents of this plant can be explored further to investigate its wide variety of therapeutic potential.

Microglial phagocytosis is an energetically demanding process that plays a critical role in the removal of toxic protein aggregates in Alzheimer's disease (AD). Recent evidence indicates that a switch in energy production from mitochondrial respiration to glycolysis disrupts this important protective microglial function and may provide therapeutic targets for AD. Here, we demonstrate that the translocator protein (TSPO) and a member of its mitochondrial complex, hexokinase-2 (HK), play critical roles in microglial respiratory-glycolytic metabolism and phagocytosis. Pharmacological and genetic loss-of-function experiments showed that TSPO is critical for microglial respiratory metabolism and energy supply for phagocytosis, and its expression is enriched in phagocytic microglia of AD mice. Meanwhile, HK controlled glycolytic metabolism and phagocytosis via mitochondrial binding or displacement. In cultured microglia, TSPO deletion impaired mitochondrial respiration and increased mitochondrial recruitment of HK, inducing a switch to glycolysis and reducing phagocytosis. To determine the functional significance of mitochondrial HK recruitment, we developed an optogenetic tool for reversible control of HK localization. Displacement of mitochondrial HK inhibited glycolysis and improved phagocytosis in TSPO-knockout microglia. Mitochondrial HK recruitment also coordinated the inflammatory switch to glycolysis that occurs in response to lipopolysaccharide in normal microglia. Interestingly, cytosolic HK increased phagocytosis independent of its metabolic activity, indicating an immune signaling function. Alzheimer's beta amyloid drastically stimulated mitochondrial HK recruitment in cultured microglia, which may contribute to microglial dysfunction in AD. Thus, targeting mitochondrial HK may offer an immunotherapeutic approach to promote phagocytic microglial function in AD.

Fatty infiltration in pancreas leading to steatosis is a major risk factor in pancreas transplantation. Hematoxylin and eosin (H and E) is one of the common histological staining techniques that provides information on the tissue cytoarchitecture. Adipose (fat) cells accumulation in pancreas has been shown to impact beta cell survival, its endocrine function and pancreatic steatosis and can cause non-alcoholic fatty pancreas disease (NAFPD). The current automated tools (E.g. Adiposoft) available for fat analysis are suited for white fat tissue which is homogeneous and easier to segment unlike heterogeneous tissues such as pancreas where fat cells continue to play critical physiopathological functions. The currently, available pancreas segmentation tool focuses on endocrine islet segmentation based on cell nuclei detection for diagnosis of pancreatic cancer. In the current study, we present a fat quantifying tool, Fatquant, which identifies fat cells in heterogeneous H and E tissue sections with reference to diameter of fat cell. Using histological images from a public database, we observed an intersection over union of 0.797 to 0.962 and 0.675 to 0.937 for manual versus Fatquant analysis of pancreas and liver, respectively., 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., (© 2023 The Author(s).)

Protein kinases are enzymes that transfer phosphate to protein, resulting in the modification of the protein. The human genome encodes approximately 538 kinases. Kinases play a role in maintaining a number of cellular processes, including control of the cell cycle, metabolism, survival, and differentiation. Protein kinase dysregulation causes several diseases, and it has been shown that numerous kinases are deregulated in cancer. The oncogenic potential of these kinases is increased by a number of processes, including overexpression, relocation, fusion point mutations, and the disruption of upstream signaling. Understanding of the mechanism or role played by kinases has led to the development of a large number of kinase inhibitors with promising clinical benefits. In this review, we discuss FDA-approved kinase inhibitors and their mechanism, clinical benefits, and side effects, as well as the challenges of overcoming some of their side effects and future prospects for new kinase inhibitor discovery., 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 Naik and Shakya.)

Research on natural products mainly focuses on developing a suitable drug to treat human disease. There has been a sharp increase in the development of drugs from natural products. Most of the drugs that are available are from the terrestrial origin. Marine natural products are less explored. Oceans are considered as a vast ecosystem with a wide variety of living organisms and natural products that are unexplored. Large numbers of antitumor drugs are from natural sources such as plants, marine, and microorganisms. 80% new chemical entities that were launched over the past 60 decades were from a natural source. In this article, the anticancer potential from the natural source such as plants, fungi, microorganisms, marine, and endophytes has been reviewed. Emphasis is given on the compound from the marine, plant, and of bacterial origin. Finally, we consider the future and how we might achieve better sustainability to alleviate human cancer suffering while having fewer side effects, more efficacies, and causing less harm than the present treatments., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2022 Ashok K. Shakya and Rajashri R. Naik.)

Sterculia diversifolia , widely distributed in Jordan as an ornamental plant, is a synonoum for Brachychiton populneus . Phytochemical studies examining the volatile chemicals in Sterculia diversifolia leaves are limited, despite the rising demand for their numerous applications. Furthermore, it was only recently that a report described the friendly synthesis of silver nanoparticles (AgNPs) using aqueous extract derived from Brachychiton populneus leaves. Therefore, AgNPs were produced using either aqueous plant extracts (AgWPE) or ethanolic plant extracts (AgEPE), and Shimadzu GC-MS equipment was used to detect volatile compounds in the ethanolic leaf extracts. GC-MS profile of leaf ethanolic extracts of the Jordanian chemotypes of S. diversifolia revealed the existence of major components: (3β)-Lup-20(29)-en-3-ol acetate (30.97%) and 1-octadecyne (24.88). Other compounds are squalene (7.19%), germanicol (6.23), dl-α-tocopherol (5.24), heptacosane (4.41), phytol (3.54) and pentacosane (2.89). According to published studies, these reported chemicals have numerous uses, including as animal feed, vitamin precursors, possible eco-friendly herbicides, antioxidants, and anti-inflammatory agents. Aqueous extracts of S. diversifolia leaves had total phenolic of 5.33 mg GAE/g extract and flavonoid contents of 64.88 mg QE/g extract, respectively. The results indicated the contribution of phenolic and flavonoids to this plant's anti-inflammatory and antioxidant properties. The reduction in AgNO 3 to AgNPs using S. diversifolia leaf extracts was confirmed by the change in solution color from colorless to dark black. Further characterization was attempted by X-ray diffraction, Malvern zeta-sizer and scanning electron microscope. The efficacy of synthesized Ag nanoparticles using aqueous or ethanolic plant extract of S. diversifolia against the Gram-negative bacteria Escherichia coli and Gram-positive bacteria Staphylococcus aureus showed appreciable activity at 25 µg/mL concentration compared to the source plant extracts.

Sclerotization of the Nereis virens jaw is mediated by metal binding to the histidine-rich jaw protein, Nvjp-1. Previous studies showed that the mechanical properties of Nvjp-1 hydrogels could be modulated with zinc binding as well as the associated anion. Here, we show that the mechanical properties of Nvjp-1 hydrogels can be modulated by pH and that zinc binding to Nvjp-1 is stable at both acidic and alkaline pH conditions. To probe the mechanism of Zn 2+ binding to Nvjp-1 at different pH conditions, we utilized all atom molecular dynamics simulations employing a polarizable force field. At low pH conditions, polar residues predominantly interacted with Zn 2+ , with at most two residues interacting with a given zinc ion. Surprisingly, little to no Zn 2+ binding was observed with the abundant Nvjp-1 acidic residues, which form salt-bridges with the protonated histidines to effectively block their binding to Zn 2+ ions. As the pH was shifted to alkaline conditions, Zn 2+ binding residues reconfigured to form additional coordination bonds with histidine, resulting in a reduction in the radius of gyration that correlated with hydrogel sclerotization. Furthermore, acetate ions were shown to facilitate the capture of zinc ions through association with protonated histidines at low pH, freeing acidic residues to interact with Zn 2+ ions and increasing the number of Zn 2+ ions that diffuse into the Nvjp-1 interior. Thus, these studies provide valuable molecular insights into how amino acid residues in Nvjp-1 manage metal salt binding and coordination in hydrogels as a function of the pH and ionic environments.

Spine surgeries are vulnerable to wrong-level surgeries and postoperative complications because of their complex structure. Unavailability of the 3D intraoperative imaging device, low-contrast intraoperative X-ray images, variable clinical and patient conditions, manual analyses, lack of skilled technicians, and human errors increase the chances of wrong-site or wrong-level surgeries. State of the art work refers 3D-2D image registration systems and other medical image processing techniques to address the complications associated with spine surgeries. Intensity-based 3D-2D image registration systems had been widely practiced across various clinical applications. However, these frameworks are limited to specific clinical conditions such as anatomy, dimension of image correspondence, and imaging modalities. Moreover, there are certain prerequisites for these frameworks to function in clinical application, such as dataset requirement, speed of computation, requirement of high-end system configuration, limited capture range, and multiple local maxima. A simple and effective registration framework was designed with a study objective of vertebral level identification and its pose estimation from intraoperative fluoroscopic images by combining intensity-based and iterative control point (ICP)-based 3D-2D registration. A hierarchical multi-stage registration framework was designed that comprises coarse and finer registration. The coarse registration was performed in two stages, i.e., intensity similarity-based spatial localization and source-to-detector localization based on the intervertebral distance correspondence between vertebral centroids in projected and intraoperative X-ray images. Finally, to speed up target localization in the intraoperative application, based on 3D-2D vertebral centroid correspondence, a rigid ICP-based finer registration was performed. The mean projection distance error (mPDE) measurement and visual similarity between projection image at finer registration point and intraoperative X-ray image and surgeons' feedback were held accountable for the quality assurance of the designed registration framework. The average mPDE after peak signal to noise ratio (PSNR)-based coarse registration was 20.41mm. After the coarse registration in spatial region and source to detector direction, the average mPDE reduced to 12.18mm. On finer ICP-based registration, the mean mPDE was finally reduced to 0.36 mm. The approximate mean time required for the coarse registration, finer registration, and DRR image generation at the final registration point were 10 s, 15 s, and 1.5 min, respectively. The designed registration framework can act as a supporting tool for vertebral level localization and its pose estimation in an intraoperative environment. The framework was designed with the future perspective of intraoperative target localization and its pose estimation irrespective of the target anatomy., (© 2022. The Author(s).)

Emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its current worldwide spread have caused a pandemic of acute respiratory disease COVID-19. The virus can result in mild to severe, and even to fatal respiratory illness in humans, threatening human health and public safety. The spike (S) protein on the surface of viral membrane is responsible for viral entry into host cells. The discovery of methods to inactivate the entry of SARS-CoV-2 through disruption of the S protein binding to its cognate receptor on the host cell is an active research area. To explore other prevention strategies against the quick spread of the virus and its mutants, non-equilibrium molecular dynamics simulations have been employed to explore the possibility of manipulating the structure-activity of the SARS-CoV-2 spike glycoprotein by applying electric fields (EFs) in both the protein axial directions and in the direction perpendicular to the protein axis. We have found out the application of EFs perpendicular to the protein axis is most effective in denaturing the HR2 domain which plays critical role in viral-host membrane fusion. This finding suggests that varying irradiation angles may be an important consideration in developing EF based non-invasive technologies to inactivate the virus., (© 2022. The Author(s).)

Pedicle screw insertion is considered a complex surgery among Orthopaedics surgeons. Exclusively to prevent postoperative complications associated with pedicle screw insertion, various types of image intensity registration-based navigation systems have been developed. These systems are computation-intensive, have a small capture range and have local maxima issues. On the other hand, deep learning-based techniques lack registration generalizability and have data dependency. To overcome these limitations, a patient-specific hybrid 3D-2D registration principled framework was designed to map a pedicle screw trajectory between intraoperative X-ray image and preoperative CT image. An anatomical landmark-based 3D-2D Iterative Control Point (ICP) registration was performed to register a pedicular marker pose between the X-ray images and axial preoperative CT images. The registration framework was clinically validated by generating projection images possessing an optimal match with intraoperative X-ray images at the corresponding control point registration. The effectiveness of the registered trajectory was evaluated in terms of displacement and directional errors after reprojecting its position on 2D radiographic planes. The mean Euclidean distances for the Head and Tail end of the reprojected trajectory from the actual trajectory in the AP and lateral planes were shown to be 0.6-0.8 mm and 0.5-1.6 mm, respectively. Similarly, the corresponding mean directional errors were found to be 4.90 and 20. The mean trajectory length difference between the actual and registered trajectory was shown to be 2.67 mm. The approximate time required in the intraoperative environment to axially map the marker position for a single vertebra was found to be 3 min. Utilizing the markerless registration techniques, the designed framework functions like a screw navigation tool, and assures the quality of surgery being performed by limiting the need of postoperative CT.

Corona virus is quickly spreading around the world. The goal of viral management is to disrupt the virus's life cycle, minimize lung damage, and alleviate severe symptoms. Numerous strategies have been used, including repurposing existing antivirals or drugs used in previous viral outbreaks. One such strategy is to repurpose FDA-approved kinase inhibitors that are potential chemotherapeutic agents and have demonstrated antiviral activity against a variety of viruses, including MERS, SARS-CoV-1, and others, by inhibiting the viral life cycle and the inflammatory response associated with COVID-19. The purpose of this article is to identify licensed kinase inhibitors that have the ability to reduce the virus's life cycle, from entrance through viral propagation from cell to cell. Several of these inhibitors, including imatinib, ruxolitinib, silmitasertib, and tofacitinib (alone and in conjunction with hydroxychloroquine), are now undergoing clinical studies to determine their efficacy as a possible treatment drug. The FDA approved baricitinib (a Janus kinase inhibitor) in combination with remdesivir for the treatment of COVID-19 patients receiving hospital care in November 2020. While in vitro trials with gilteritinib, fedratinib, and osimertinib are encouraging, further research is necessary before these inhibitors may be used to treat COVID-19 patients., 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 © 2022 Naik, Shakya, Aladwan and El-Tanani.)

Novel methods that enable facile, ultrasensitive and multiplexed detection of low molecular weight organic compounds such as metabolites, drugs, additives, and organic pollutants are valuable in biomedical research, clinical diagnosis, food safety and environmental monitoring. Here, we demonstrate a simple, rapid, and ultrasensitive method for detection and quantification of small molecules by implementing a competitive immunoassay with an ultrabright fluorescent nanolabel, plasmonic fluor. Plasmonic-fluor is comprised of a polymer-coated gold nanorod and bovine serum albumin conjugated with molecular fluorophores and biotin. The synthesis steps and fluorescence emission of plasmonic-fluor was characterized by UV-vis spectroscopy, transmission electron microscopy, and fluorescence microscopy. Plasmon-enhanced competitive assay can be completed within 20 min and exhibited more than 30-fold lower limit-of-detection for cortisol compared to conventional competitive ELISA. The plasmon-enhanced competitive immunoassay when implemented as partition-free digital assay enabled further improvement in sensitivity. Further, spatially multiplexed plasmon-enhanced competitive assay enabled the simultaneous detection of two analytes (cortisol and fluorescein). This simple, rapid, and ultrasensitive method can be broadly employed for multiplexed detection of various small molecules in research, in-field and clinical settings., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Human health and performance monitoring (HHPM) is imperative to provide information necessary for protecting, sustaining, evaluating, and improving personnel in various occupational sectors, such as industry, academy, sports, recreation, and military. While various commercially wearable sensors are on the market with their capability of "quantitative assessments" on human health, physical, and psychological states, their sensing is mostly based on physical traits, and thus lacks precision in HHPM. Minimally or noninvasive biomarkers detectable from the human body, such as body fluid (e.g., sweat, tear, urine, and interstitial fluid), exhaled breath, and skin surface, can provide abundant additional information to the HHPM. Detecting these biomarkers with novel or existing sensor technologies is emerging as critical human monitoring research. This review provides a broad perspective on the state of the art biosensor technologies for HHPM, including the list of biomarkers and their physiochemical/physical characteristics, fundamental sensing principles, and high-performance sensing transducers. Further, this paper expands to the additional scope on the key technical challenges in applying the current HHPM system to the real field., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)

As a result of the COVID-19 pandemic, nations across the globe have responded by attempting to understand how the virus was spreading in their communities, in order to isolate cases, reduce morbidity and mortality, and avoid overwhelming healthcare facilities. In this article, we describe the global response to tracking the virus and discuss new technological advances in molecular testing that have been deployed and developed to track and mitigate COVID-19. We also discuss how the successes and failures observed in the COVID-19 pandemic can be extrapolated to improve our ability to respond to the next pandemic.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has rapidly spread and resulted in the global pandemic of COVID-19. Although IgM/IgG serology assay has been widely used, with the entire spike or nucleocapsid antigens, they only indicate the presence or absence of antibodies against these proteins but are not specific to the neutralization antibodies, therefore providing only generic information about infection stage and possible future immune protection. Novel technologies enabling easy-to-use and sensitive detection of multiple specific antibodies simultaneously will facilitate precise diagnosis of infection stage, prediction of clinical outcomes, and evaluation of future immune protection upon viral exposure or vaccination. Here, we demonstrate a rapid and ultrasensitive quantification method for epitope-specific antibodies, including different isotypes and subclasses, in a multiplexed manner. Using an ultrabright fluorescent nanolabel, plasmonic-fluor, this novel assay can be completed in 20 min and more importantly, the limit of detection of the plasmon-enhanced immunoassay for SARS-CoV-2 antibodies is as much as 100-fold lower compared to the assays relying on enzymatic amplification of colorimetric signals. Using convalescent patient plasma, we demonstrate that this biodetection method reveals the patient-to-patient variability in immune response as evidenced by the variations in whole protein and epitope-specific antibodies. This cost-effective, rapid, and ultrasensitive plasmonically enhanced multiplexed epitope-specific serological assay has the potential to be broadly employed in the detection of specific antibodies, which may benefit the advanced epidemiology studies and enable improvement of the clinical outcomes and prediction of the future protection against the SARS-CoV-2.

The involvement of cancer stem cells (CSCs) in driving tumor dormancy and drug resistance is well established. Most therapeutic regimens however are ineffective in targeting these regenerative populations. We report the development and evaluation of a monoclonal antibody, mAb150, which targets the metastasis associated antigen, Annexin A2 (AnxA2) through recognition of a N-terminal epitope. Treatment with mAb150 potentiated re-entry of CSCs into the cell cycle that perturbed tumor dormancy and facilitated targeting of CSCs as was validated by in vitro and in vivo assays. Epigenetic potentiation further improved mAb150 efficacy in achieving total tumor regression by targeting regenerative populations to achieve tumor regression, specifically in high-grade serous ovarian adenocarcinoma., (Copyright © 2021. Published by Elsevier Inc.)

Plant-derived protein research has gained attention in recent years due to the rise of health concerns, allergenicity, trends toward vegan diet, food safety, and sustainability; but the lower techno-functional attributes of plant proteins compared to those of animals still remain a challenge for their utilization. Maillard conjugation is a protein side-chain modification reaction which is spontaneous, and do not require additional chemical additive to initiate the reaction. The glycoconjugates formed during the reaction significantly improves the thermal stability and pH sensitivity of proteins. The modification of plant-derived protein using Maillard conjugation requires a comprehensive understanding of the influence of process conditions on the conjugation process. These factors can be used to establish a correlation with different functional and bioactive characteristics, to potentially adapt this approach for selective functionality enhancement and nutraceutical development. This review covers recent advances in plant-derived protein modification using Maillard conjugation, including different pretreatments to modify the functionality and bioactivity of plant proteins and their potential uses in practice. An overview of different properties of conjugates and MRPs, including food safety aspects, is given.

Novel methods that enable sensitive, accurate and rapid detection of RNA would not only benefit fundamental biological studies but also serve as diagnostic tools for various pathological conditions, including bacterial and viral infections and cancer. Although highly sensitive, existing methods for RNA detection involve long turn-around time and extensive capital equipment. Here, an ultrasensitive and amplification-free RNA quantification method is demonstrated by integrating CRISPR-Cas13a system with an ultrabright fluorescent nanolabel, plasmonic fluor. This plasmonically enhanced CRISPR-powered assay exhibits nearly 1000-fold lower limit-of-detection compared to conventional assay relying on enzymatic reporters. Using a xenograft tumor mouse model, it is demonstrated that this novel bioassay can be used for ultrasensitive and quantitative monitoring of cancer biomarker (lncRNA H19). The novel biodetection approach described here provides a rapid, ultrasensitive, and amplification-free strategy that can be broadly employed for detection of various RNA biomarkers, even in resource-limited settings., (© 2021 Wiley-VCH GmbH.)

The present paper reports the GC-HS-SPME analysis of volatile emission and GC-MS analysis of chemical composition of essential oil of R. coriaria fruits of eight different samples of R. coriaria L. fruits ("sumac" folk name), collected from Jordanian agricultural field and the local market. The analyses show an important variability among the Sumac samples probably due to the origin, cultivation, harvesting period, drying, and conservation of the plant material. The main class of component present in all samples was monoterpenes (43.1 to 72.9%), except for one sample which evidenced a high percentage of sesquiterpene hydrocarbons (38.5%). The oxygenated monoterpenes provided a contribution to total class of monoterpenes ranging from 10.1 to 24.3%. A few samples were rich in monoterpene hydrocarbons. Regarding the single components present in all the volatile emissions, β-caryophyllene was the main compound in most of the analyzed samples, varying from 34.6% to 7.9%. Only two samples were characterized by α-pinene as the main constituent (42.2 and 40.8% respectively). Essential oils were collected using hydro-distillation method. Furfural was the main constituent in almost all the analyzed EOs (4.9 to 48.1%), except in one of them, where β-caryophyllene was the most abundant one. β-caryophyllene ranged from 1.2 to 10.6%. Oxygenated monoterpenes like carvone and carvacrol ranged from 3.2-9.1% and 1.0-7.7% respectively. Cembrene was present in good amount in EO samples EO-2 to EO-8. The antioxidant capacities of the fruit essential oils from R. coriaria were assessed using spectrophotometry to measure free radical scavenger 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical and inhibition of β-carotene bleaching (BCB). The essential oils from the fruits of the different samples of R. coriaria exhibited the MIC value ranging from 32.8 to 131.25 µg/mL against S. aureus ATCC 6538 and 131.25 to 262.5 µg/mL against E. coli ATCC 8739 . The MIC values of ciprofloxacin were 0.59 and 2.34 µg/mL against S. aureus ATCC 6538 and E. coli ATCC 8739 , respectively.

Enzyme-linked immunosorbent assay is widely utilized in serologic assays, including COVID-19, for the detection and quantification of antibodies against SARS-CoV-2. However, due to the limited stability of the diagnostic reagents (e.g., antigens serving as biorecognition elements) and biospecimens, temperature-controlled storage and handling conditions are critical. This limitation among others makes biodiagnostics in resource-limited settings, where refrigeration and electricity are inaccessible or unreliable, particularly challenging. In this work, metal-organic framework encapsulation is demonstrated as a simple and effective method to preserve the conformational epitopes of antigens immobilized on microtiter plate under non-refrigerated storage conditions. It is demonstrated that in situ growth of zeolitic imidazolate framework-90 (ZIF-90) renders excellent stability to surface-bound SARS-CoV-2 antigens, thereby maintaining the assay performance under elevated temperature (40 °C) for up to 4 weeks. As a complementary method, the preservation of plasma samples from COVID-19 patients using ZIF-90 encapsulation is also demonstrated. The energy-efficient approach demonstrated here will not only alleviate the financial burden associated with cold-chain transportation, but also improve the disease surveillance in resource-limited settings with more reliable clinical data., (© 2021 Wiley-VCH GmbH.)

Protein ionic liquids (PIL) are a new class of biologic stabilizers designed to protect the functionality and extend the shelf-life of biotechnological and therapeutic agents making them more readily available, and resistant to austere environments. Protein biorecognition elements such as monoclonal antibodies are commonly utilized therapeutics that require the robust stabilization offered by PILs, but biocompatibility remains an important issue. This study has focused on characterizing the biocompatibility of an antibody based PIL by exposing multiple cells types to a cationized immunoglobulin suspended in an anionic liquid (IgG-IL). The IgG-IL caused no significant alterations in cellular health for all three cell types with treatments < 12.5 µg/mL. Concentrations ≥ 12.5 µg/mL resulted in significant necrotic cell death in A549 and HaCaT cells, and caspase associated cell death in HepG2 cells. In addition, all cells displayed evidence of oxidative stress and IL-8 induction in response to IgG-IL exposures. Therapeutic Ig can be utilized with a wide dose range that extends into concentrations we have found to exhibit cytotoxicity raising a toxicity concern and a need for more extensive understanding of the biocompatibility of IgG-ILs., (© 2021. The Author(s).)

Propolis is a resinous natural product collected by honeybees ( Apis mellifera and others) from tree exudates that has been widely used in folk medicine. The present study was carried out to investigate the fatty acid composition, chemical constituents, antioxidant, and xanthine oxidase (XO) inhibitory activity of Jordanian propolis, collected from Al-Ghour, Jordan. The hexane extract of Jordanian propolis contained different fatty acids, which are reported for the first time by using GC-FID. The HPLC was carried out to identify important chemical constituents such as fatty acids, polyphenols and α-tocopherol. The antioxidant and xanthine oxidase inhibitory activities were also monitored. The major fatty acid identified were palmitic acid (44.6%), oleic acid (18:1∆ 9 cis , 24.6%), arachidic acid (7.4%), stearic acid (5.4%), linoleic acid (18:2∆ 9-12 cis , 3.1%), caprylic acid (2.9%), lignoceric acid (2.6%), cis -11,14-eicosaldienoic acid (20:2∆ 11-14 cis , 2.4%), palmitoleic acid (1.5%), cis -11-eicosenoic acid (1.2%), α-linolenic acid (18:3∆ 9-12-15 cis , 1.1%), cis -13,16-docosadienoic acid (22:2∆ 13-16 cis , 1.0%), along with other fatty acids. The major chemical constituents identified using gradient HPLC-PDA analysis were pinocembrin (2.82%), chrysin (1.83%), luteolin-7- O -glucoside (1.23%), caffeic acid (1.12%), caffeic acid phenethyl ester (CAPE, 0.79%), apigenin (0.54%), galangin (0.46%), and luteolin (0.30%); while the minor constituents were hesperidin, quercetin, rutin, and vanillic acid. The percentage of α-tocopherol was 2.01 µg/g of the lipid fraction of propolis. Antioxidant properties of the extracts were determined via DPPH radical scavenging. The DPPH radical scavenging activities (IC 50 ) of different extracts ranged from 6.13 to 60.5 µg/mL compared to ascorbic acid (1.21 µg/mL). The xanthine oxidase inhibition (IC 50 ) ranged from 75.11 to 250.74 µg/mL compared to allopurinol (0.38 µg/mL). The results indicate that the various flavonoids, phenolic compounds, α-tocopherol, and other constituents which are present in propolis are responsible for the antioxidant and xanthine oxidation inhibition activity. To evaluate the safety studies of propolis, the pesticide residues were also monitored by LC-MS-MS 4500 Q-Trap. Trace amounts of pesticide residue (ng/mL) were detected in the samples, which are far below the permissible limit as per international guidelines.

Tissue-resident macrophages in white adipose tissue (WAT) dynamically adapt to the metabolic changes of their microenvironment that are often induced by excess energy intake. Currently, the exact contribution of these macrophages in obesity-driven WAT remodeling remains controversial. Here, using a transgenic CD169-DTR mouse strain, we provide new insights into the interplay between CD169 + adipose tissue macrophages (ATMs) and their surrounding WAT microenvironment. Using targeted in vivo ATM ablation followed by transcriptional and metabolic WAT profiling, we found that ATMs protect WAT from the excessive pathological remodeling that occurs during obesity. As obesity progresses, ATMs control not only vascular integrity, adipocyte function, and lipid and metabolic derangements but also extracellular matrix accumulation and resultant fibrosis in the WAT. The protective role of ATMs during obesity-driven WAT dysfunction supports the notion that ATMs represent friends, rather than foes, as has previously assumed., (© 2021 The Authors. Published under the terms of the CC BY NC ND 4.0 license.)

The Competition-Enhanced Ligand Selection (CompELS) approach was used to identify aptamer candidates for spherical gold nanoparticles (AuNPs). This approach differs from conventional Systematic Evolution of Ligands by EXponential enrichment (SELEX)-based aptamer screening by eliminating repeated elution and polymerase chain reaction (PCR) amplification steps of bound candidate sequences between each selection round to continually enrich the candidate aptamer pool with oligonucleotides remaining from an earlier SELEX selection round. Instead, a new pool of unenriched oligonucleotides is added during each CompELS selection round to compete with existing target-bound oligonucleotides species for target binding sites. In this study, 24 aptamer candidates for AuNPs were identified using the CompELS approach and then compared to reveal similarities in their primary structures and their predicted secondary structures. No strong patterns in individual base identities (position-dependent) nor in segments of consecutive bases (independent of position) prevailed among the identified sequences. Motifs in predicted secondary structures, on the other hand, were shared among otherwise unrelated aptamer sequences. These motifs were revealed using a systematic classification and enumeration of distinct secondary structure elements, namely, hairpins, duplexes, single-stranded segments, interior loops, bulges, and multibranched loops.

Plasmon-enhanced fluorescence (PEF) is a simple and highly effective approach for improving the signal-to-noise ratio and sensitivity of various fluorescence-based bioanalytical techniques. Here, we show that the fluorescence enhancement efficacy of gold nanorods (AuNRs), which are widely employed for PEF, is highly dependent on their absolute dimensions (i.e., length and diameter). Notably, an increase in the dimensions (length × diameter) of the AuNRs from 46 × 14 to 120 × 38 nm 2 while holding the aspect ratio constant leads to nearly 300% improvement in fluorescence enhancement efficiency. Further increase in the AuNR size leads to a decrease of the fluorescence enhancement efficiency. Through finite-difference time-domain (FDTD) simulation, we reveal that the size-dependent fluorescence enhancement efficiency of AuNR stems from the size-dependent electromagnetic field around the plasmonic nanostructures. AuNRs with optimal dimensions resulted in a nearly 120-fold enhancement in the ensemble fluorescence emission from molecular fluorophores bound to the surface. These plasmonic nanostructures with optimal dimensions also resulted in a nearly 30-fold improvement in the limit of detection of human interleukin-6 (IL-6) compared to AuNRs with smaller size, which are routinely employed in PEF.

Since December 2019, SARS-CoV-2 (COVID-19), novel corona virus has caused pandemic globally, with rise in the number of cases and death of the patients. Vast majority of the countries that are dealing with rise in the active cases and death of patients suffering from novel corona viruses COVID-19 are trying to content the virus by isolating the patients and treating them with the approved antiviral that have been previously used in treating SARS, MERS, and drugs that are used to treat other viral infections. Some of these are under clinical trials. At present there are no therapeutically effective antiviral present and there are no vaccines or drugs available that are clinically approved for treating the corona virus. The current strategy is to re-purpose the available drugs or antiviral that can minimise or reduce the burden of the health care emergencies. In this article the reuse of antiviral, US-FDA approved drugs, plant based therapeutic, anti-malarial, anti-parasitic, anti-HIV drugs and the traditional medicines that are being currently used in treating the symptoms of COVID-19 patients is discussed emphasis is also given on the treatment using monoclonal antibodies. The present article provides the therapeutic strategies that will qualify as one of the best available treatment for the better management of the COVID-19 patients in order to achieve medical benefits., 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 © 2021 Naik and Shakya.)

Bio-inspired approaches represent potentially transformational methods to fabricate and activate non-natural materials for applications ranging from biomedical diagnostics to energy harvesting platforms. Recently, bio-based methods for the exfoliation of graphene in water have been developed, resulting in peptide-capped nanosheets; however, a clear understanding of the reaction system and peptide ligand structure remains unclear, limiting the advance of such approaches. Here the effects of reaction solution conditions and peptide ligand structure were systematically examined for graphene exfoliation, identifying key parameters to optimize material production. For this, the P1 peptide, identified with affinity for graphene, was exploited to drive exfoliation of bulk graphite to generate the final materials. The peptide was modified at both the N- and C-terminus with a 10-carbon chain fatty acid to explore the effects of a hydrophobic domain on the exfoliation process. The system was examined as a function of sonication time, pH, reagent concentration, and graphite source, where the final materials were fully characterized using a suite of approaches. Collectively, these results demonstrated that maximum graphene production was achieved using the parent P1 peptide after 12 h of sonication under basic conditions. While the exfoliation efficiency was slightly lower for the fatty acid modified peptides, the graphene produced using these biomolecules had fewer defects incorporated, potentially from the wrapping of the nanosheet edge by the aliphatic domain. Such results are important to provide key reaction designs to optimize the reproducibility of graphene exfoliation using biomimetic approaches.

COVID-19 is a highly contagious and widespread disease that has strained the global healthcare system to the hilt. Silver nanoparticles (AgNPs) are well known for their potent antimicrobial, antiviral, immunomodulatory and biosensing properties. AgNPs have been found to be potential antiviral agent that act against many deadly viruses and is presumed to be effective against COVID-19. AgNPs can generate free radicals and reactive oxygen species (ROS) leading to apoptosis mediated cell death thereby inhibiting viral infection. The shape and size of AgNPs play an important role in its biomedical applications as alterations may result in variable biological interaction and activity. Herein, we propose that AgNPs can be utilized for effective management of the ongoing COVID-19 pandemic by highlighting the current status of AgNPs in the fight against COVID-19., 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., (© 2021 The Authors.)

Structural proteins such as "suckerins" present promising avenues for fabricating functional materials. Suckerins are a family of naturally occurring block copolymer-type proteins that comprise the sucker ring teeth of cephalopods and are known to self-assemble into supramolecular networks of nanoconfined β-sheets. Here, we report the characterization and controllable, nanoscale self-assembly of suckerin-12 (S12). We characterize the impacts of salt, pH, and protein concentration on S12 solubility, secondary structure, and self-assembly. In doing so, we identify conditions for fabricating ∼100 nm nanoassemblies (NAs) with narrow size distributions. Finally, by installing a noncanonical amino acid (ncAA) into S12, we demonstrate the assembly of NAs that are covalently conjugated with a hydrophobic fluorophore and the ability to change self-assembly and β-sheet content by PEGylation. This work presents new insights into the biochemistry of suckerin-12 and demonstrates how ncAAs can be used to expedite and fine-tune the design of protein materials.

A fundamental problem in thermodynamics is the recovery of macroscopic equilibrated interaction energies from experimentally measured single-molecular interactions. The Jarzynski equality forms a theoretical basis in recovering the free energy difference between two states from exponentially averaged work performed to switch the states. In practice, the exponentially averaged work value is estimated as the mean of finite samples. Numerical simulations have shown that samples having thousands of measurements are not large enough for the mean to converge when the fluctuation of external work is above 4 k B T, which is easily observable in biomolecular interactions. We report the first example of a statistical gamma work distribution applied to single molecule pulling experiments. The Gibbs free energy of surface adsorption can be accurately evaluated even for a small sample size. The values obtained are comparable to those derived from multi-parametric surface plasmon resonance measurements and molecular dynamics simulations.

Nanosheet heterostructures offer emergent optical/electronic properties. These could be achieved using selective materials binding peptides, but lack of understanding of selectivity impedes advancement. Here we examine peptides with affinity for graphene or h-BN using quantitative experiments and molecular simulation to identify traits for design of 2D nanosheet selective peptides.

Precise monitoring of specific biomarkers in biological fluids with accurate biodiagnostic sensors is critical for early diagnosis of diseases and subsequent treatment planning. In this work, we demonstrated an innovative biodiagnostic sensor, portable reusable accurate diagnostics with nanostar antennas (PRADA), for multiplexed biomarker detection in small volumes (~50 μl) enabled in a microfluidic platform. Here, PRADA simultaneously detected two biomarkers of myocardial infarction, cardiac troponin I (cTnI), which is well accepted for cardiac disorders, and neuropeptide Y (NPY), which controls cardiac sympathetic drive. In PRADA immunoassay, magnetic beads captured the biomarkers in human serum samples, and gold nanostars (GNSs) "antennas" labeled with peptide biorecognition elements and Raman tags detected the biomarkers via surface-enhanced Raman spectroscopy (SERS). The peptide-conjugated GNS-SERS barcodes were leveraged to achieve high sensitivity, with a limit of detection (LOD) of 0.0055 ng/ml of cTnI, and a LOD of 0.12 ng/ml of NPY comparable with commercially available test kits. The innovation of PRADA was also in the regeneration and reuse of the same sensor chip for ~14 cycles. We validated PRADA by testing cTnI in 11 de-identified cardiac patient samples of various demographics within a 95% confidence interval and high precision profile. We envision low-cost PRADA will have tremendous translational impact and be amenable to resource-limited settings for accurate treatment planning in patients., Competing Interests: The authors declare no competing interest., (© 2020 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of The American Institute of Chemical Engineers.)

The use of biomolecules has been invaluable at generating and controlling optical chirality in nanomaterials; however, the structure and properties of the chiral biotemplate are not well understood due to the complexity of peptide-nanoparticle interactions. In this study, we show that the complex interactions between d-peptides and gold nanomaterials led to a chiral restructuring of peptides as demonstrated by circular dichroism and proteolytic cleavage of d-peptides via gold-mediated inversion of peptide chirality. The gold nanoparticles synthesized using d-peptide produce a highly ordered atomic surface and restructured peptide bonds for enzyme cleavage. Differences in gold nanoparticle catalyzed reduction of 4-nitrophenol were observed on the basis of the chiral peptide used in nanoparticle synthesis. Notably, the proteolytic cleavage of d-peptides on gold provides an opportunity for designing nanoparticle based therapeutics to treat peptide venoms, access new chemistries, or modulate the catalytic activity of nanomaterials.

Minicollagens from cnidarian nematocysts are attractive potential building blocks for the creation of strong, lightweight and tough polymeric materials with the potential for dynamic and reconfigurable crosslinking to modulate functionality. In this study, the Hydra magnipapillata minicollagen-1 isoform was recombinantly expressed in bacteria, and a high throughput purification protocol was developed to generate milligram levels of pure protein without column chromatography. The resulting minicollagen-1 preparation demonstrated spectral properties similar to those observed with collagen and polyproline sequences as well as the ability to self-assemble into oriented fibers and bundles. Photo-crosslinking with Ru(II) ( bpy ) 3 2 + was used to create robust hydrogels that were analyzed by mechanical testing. Interestingly, the minicollagen-1 hydrogels could be dissolved with reducing agents, indicating that ruthenium-mediated photo-crosslinking was able to induce disulfide metathesis to create the hydrogels. Together, this work is an important first step in creating minicollagen-based materials whose properties can be manipulated through static and reconfigurable post-translational modifications., (Copyright © 2020 Farajollahi, Dennis, Crosby, Slocik, Pelton, Hampton, Drummy, Yang, Silberstein, Gupta and Naik.)

Wearable sensors for human health, performance, and state monitoring, which have a linear response to the binding of biomarkers found in sweat, saliva, or urine, are of current interest for many applications. A critical part of any device is a biological recognition element (BRE) that is able to bind a biomarker at the surface of a sensor with a high affinity and selectivity to produce a measurable signal response. In this study, we discover and compare 12-mer peptides that bind to neuropeptide Y (NPY), a stress and human health biomarker, using independent and complimentary experimental and computational approaches. The affinities of the NPY-binding peptides discovered by both methods are equivalent and below the micromolar level, which makes them suitable for application in sensors. The in silico design protocol for peptide-based BREs is low cost, highly efficient, and simple, suggesting its utility for discovering peptide binders to a variety of biomarker targets.

Molecular dynamics simulation was performed on sugar profile and moisture content-based mixture systems of six Indian honey samples. Comparative studies were performed to understand the interactive effects of fructose, glucose, sucrose, maltose and water on crystallization. All simulations led to formation of stable crystal but with different interaction energies. Post-simulation analysis showed that Fructose:Glucose of 1.18 formed the most stable crystal with highest van der Waals and electrostatic interactions. The stability of crystal was further validated with least gyration radius (209 ± 1.81 nm 2 ), accessible surface area (4.09 ± 0.04 nm) and root mean square displacement (3.51 ± 0.00261 nm). Results indicated that not only Fructose:Glucose ratio but also sucrose, maltose and water had a significant effect on the overall crystallization process. The simulation data was used to train the artificial neural network which predicted the stability of honey crystallization depending on Fructose:Glucose and Glucose:Water ratios., (Copyright © 2019 Elsevier Ltd. All rights reserved.)