Computational Frontiers in Aptamer-Based Nanomedicine for Precision Therapeutics: A Comprehensive Review.

In the rapidly evolving landscape of nanomedicine, aptamers have emerged as powerful molecular tools, demonstrating immense potential in targeted therapeutics, diagnostics, and drug delivery systems. This paper explores the computational features of aptamers in nanomedicine, highlighting their advantages over antibodies, including selectivity, low immunogenicity, and a simple production process. A comprehensive overview of the aptamer development process, specifically the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) process, sheds light on the intricate methodologies behind aptamer selection. The historical evolution of aptamers and their diverse applications in nanomedicine are discussed, emphasizing their pivotal role in targeted drug delivery, precision medicine and therapeutics. Furthermore, we explore the integration of artificial intelligence (AI), machine learning (ML), Internet of Things (IoT), Internet of Medical Things (IoMT), and nanotechnology in aptameric development, illustrating how these cutting-edge technologies are revolutionizing the selection and optimization of aptamers for tailored biomedical applications. This paper also discusses challenges in computational methods for advancing aptamers, including reliable prediction models, extensive data analysis, and multiomics data incorporation. It also addresses ethical concerns and restrictions related to AI and IoT use in aptamer research. The paper examines progress in computer simulations for nanomedicine. By elucidating the importance of aptamers, understanding their superiority over antibodies, and exploring the historical context and challenges, this review serves as a valuable resource for researchers and practitioners aiming to harness the full potential of aptamers in the rapidly evolving field of nanomedicine.

Glassy dynamics in a liquid of anisotropic molecules: Bifurcation of relaxation spectrum.

In experimental and theoretical studies of glass transition phenomena, one often finds a sharp crossover in dynamical properties at a temperature Tcr. A bifurcation of a relaxation spectrum is also observed at a temperature TB≈Tcr; both lie significantly above the glass transition temperature. In order to better understand these phenomena, we introduce a new model of glass-forming liquids, a binary mixture of prolate and oblate ellipsoids. This model system exhibits sharp thermodynamic and dynamic anomalies, such as the specific heat jump during heating and a sharp variation in the thermal expansion coefficient around a temperature identified as the glass transition temperature, Tg. The same temperature is obtained from the fit of the calculated relaxation times to the Vogel-Fulcher-Tammann (VFT) form. As the temperature is lowered, the calculated single peak rotational relaxation spectrum splits into two peaks at TB above the estimated Tg. Similar bifurcation is also observed in the distribution of short-to-intermediate time translational diffusion. Interrogation of the two peaks reveals a lower extent of dynamic heterogeneity in the population of the faster mode. We observe an unexpected appearance of a sharp peak in the product of rotational relaxation time τ2 and diffusion constant D at a temperature Tcr, close to TB, but above the glass transition temperature. Additionally, we coarse-grain the system into cubic boxes, each containing, on average, ∼62 particles, to study the average dynamical properties. Clear evidence of large-scale sudden changes in the diffusion coefficient and rotational correlation time signals first-order transitions between low and high-mobility domains.

Ultrafast Dynamics of Self-Trapped Excitons in Cs2AgInCl6:Al3+ Double Perovskite Nanocrystals.

It is a huge challenge to increase the photoluminescence (PL) of lead-free halide perovskites, and understanding the mechanism behind exciton dynamics can provide a valuable solution. Herein, we achieved enhanced broad-band emission at ambient conditions in Cs2AgInCl6 by tuning self-trapped excitons (STEs) through Al3+ doping. Cryogenic measurements showed an inhomogeneous nature of STE emission due to the presence of defect states and is subject to thermal quenching. An increased Huang-Rhys factor (S-factor) resulted in better electron-phonon coupling and high-density STE states post Al3+ doping. Femtosecond transient absorption (fs-TA) results provided insights into the distribution dynamics of excitons, which occurs through gradient energy levels from free excitons (FE) to STEs, where each STE state potentially possesses higher quantized energy states. Overall, this study aims to comprehend the origins of self-trapping and decay of STEs in Cs2AgInCl6:Al3+ and emphasizes the potential of compositional engineering to mitigate self-trapping in this material.

Phylum-level studies of bacterial cutinases for unravelling enzymatic specificity toward PET degradation: an in silico approach.

The overwhelming use of PET plastic in various day-to-day activities led to the voluminous increase in PET waste and growing environmental hazards. A plethora of methods have been used that are associated with secondary pollutants. Therefore, microbial degradation of PET provides a sustainable approach due to its versatile metabolic diversity and capacity. The present work highlights the cutinase enzyme's role in PET degradation. This study focuses on the bacterial cutinases homologs screened from 43 reported phylum of bacteria. The reported bacterial cutinases for plastic degradation have been chosen as reference sequences, and 917 sequences have shown homology across the bacterial phyla. The dienelactone hydrolase (DLH) domain was identified for attaining specificity towards PET binding in 196 of 917 sequences. Various computational tools have been used for the physicochemical characterization of 196 sequences. The analysis revealed that most selected sequences are hydrophilic, extracellular, and thermally stable. Based on this analysis, 17 sequences have been further pursued for three-dimensional structure prediction and validation. The molecular docking studies of 17 selected sequences revealed efficient PET binding with the three sequences derived from the phylum Bacteroidota, the lowest binding energy of -5.9 kcal/mol, Armatimonadota, and Nitrososphaerota with -5.8 kcal/mol. The two enzyme sequences retrieved from the phylum Bacteroidota and Armatimonadota are metagenomically derived. Therefore, the present studies concluded that there is a high probability of finding cutinase homologs in various environmental resources that can be further explored for PET degradation.

One-Pot Synthesis of Vinylogous Cyano Aminoaryls (VinCAs) as Benzenic Fluorophores: Tailoring Diverse Emission Colors for White Light Emitting Materials and Cell Imaging.

Donor-acceptor-based organic small molecules with an electronic push-pull effect can demonstrate intramolecular charge transfer to show interesting photoluminescence properties. This is an essential criterion for designing fluorogenic probes for cell imaging studies and the development of organic light-emitting diodes. Now, to design such optical materials sometimes it is necessary to tune the band gap by controlling the energies of the highest occupied molecular orbital and lowest unoccupied molecular orbital. Typically, the band gaps could be modulated by installing unsaturated handles between electron-rich donors and electron-deficient acceptors. However, these methods are often synthetically and economically challenging due to the involvement of expensive catalysts and difficult reaction setups. In our present study, we show a straightforward, cost-effective method for obtaining a series of donor-acceptor-type Vinylogous Cyano Aminoaryls (VinCAs) with diverse emission colors. Further studies reveal that these VinCAs can serve as effective cell imaging agents, showcasing potential use in chemical biology. Additionally, these molecules could be further used to generate white light emission (WLE), showing their potential utility in advanced lighting technologies.

Model of zonular forces on the lens capsule during accommodation.

How the human eye focuses for near; i.e. accommodates, is still being evaluated after more than 165 years. The mechanism of accommodation is essential for understanding the etiology and potential treatments for myopia, glaucoma and presbyopia. Presbyopia affects 100% of the population in the fifth decade of life. The lens is encased in a semi-elastic capsule with attached ligaments called zonules that mediate ciliary muscle forces to alter lens shape. The zonules are attached at the lens capsule equator. The fundamental issue is whether during accommodation all the zonules relax causing the central and peripheral lens surfaces to steepen, or the equatorial zonules are under increased tension while the anterior and posterior zonules relax causing the lens surface to peripherally flatten and centrally steepen while maintaining lens stability. Here we show with a balloon capsule zonular force model that increased equatorial zonular tension with relaxation of the anterior and posterior zonules replicates the topographical changes observed during in vivo rhesus and human accommodation of the lens capsule without lens stroma. The zonular forces required to simulate lens capsule configuration during in vivo accommodation are inconsistent with the general belief that all the zonules relax during accommodation.

Formulation, Characterization and In Vitro Evaluation of Mesalamine and Bifidobacterium bifidum Loaded Hydrogel Beads in Capsule System for Colon Targeted Delivery.

Mesalamine is a first-line drug for the treatment of inflammatory bowel diseases. However, its premature release associated with marketed formulations leads to adverse effects like gastric trouble, vomiting, and diarrhoea. To minimize these side effects, colon-targeted drug delivery is essential. Besides conventional pharmacotherapy, bifidogenic probiotics with anti-inflammatory activity has been reported to elicit a significant impact on the remission of ulcerative colitis. Bifidogenic probiotics being acid-labile necessitate developing a gastro-resistant formulation for enhancing the delivery of viable cells to the colon. The present study was aimed at developing a fixed-dose unit dosage form of mucoadhesive hydrogel beads loaded with mesalamine and Bifidobacterium bifidum further encapsulated in Eudragit® capsules for the targeted drug delivery at colonic pH. The hydrogel beads were prepared by ionotropic gelation, with the effect of single and dual-crosslinking approaches on various formulation characteristics studied. Standard size 00 Eudragit® gastro-resistant capsules were prepared and the dried beads were filled inside the capsule shells. The formulation was then evaluated for various parameters, including physicochemical characterization, in vitro biocompatibility and anti-inflammatory activity. No interaction was observed between the drug and the polymers, as confirmed through FTIR, XRD, and DSC analysis. The mean particle size of the beads was ~ 457-485 µm. The optimized formulation showed a drug entrapment efficiency of 95.4 ± 2.58%. The Eudragit® capsule shells disintegrated in approximately 13 min at pH 7.4. The mucoadhesive hydrogel beads sustained the drug release above 18 h, with 50% of the drug released by the end of 12 h. The optimized formulation demonstrated significant (p < 0.05) gastro-resistance, biocompatibility, sustained drug release, cell viability, and anti-inflammatory activity.

New generation mixed matrix membrane for CO2 separation: Transition from binary to quaternary mixed matrix membrane.

Contemporary advances in material development associated with membrane gas separation refer to the cost-effective fabrication of high-performance, defect-free mixed matrix membranes (MMMs). For clean energy production, natural gas purification, and CO2 capture from flue gas systems, constituting a functional integration of polymer matrix and inorganic filler materials find huge applications. The broad domain of research and development of MMMs focused on the selection of appropriate materials, inexpensive membrane fabrication, and comparative study with other gas separation membranes for real-world applications. This study addressed a comprehensive review of the advanced MMMs wrapping various facets of membrane material selection; polymer and filler particle morphology and compatibility between the phases and the relevance of several fillers in the assembly of MMMs are analyzed. Further, the research on binary MMMs, their problems, and solutions to overcome these challenges have also been discussed. Finally, the future directions and scope of work on quaternary MMM are scrutinized in the article.

Noninvasive Blood Pressure Monitoring via a Flexible and Wearable Piezoresistive Sensor.

In the present global context, continuous blood pressure (BP) monitoring is paramount in addressing the global mortality rates attributed to hypertension. Achieving precise insights into the human cardiovascular system necessitates accurate measurement of BP, and the accuracy depends on the faithful recording of oscillations or pulsations. This task ultimately depends on the caliber of the pressure sensor embedded in the BP device. In this context, we have fabricated a flexible resistive pressure sensor based on reduced graphene oxide (rGO) and a polydimethylsiloxane (PDMS) sponge that is highly flexible and sensitive. The designed device operates effectively with a minimal bias voltage of 500 mV, at which point it showed its maximum relative change in current, reaching approximately 25%. Additionally, the sensing device showed a notable change in resistance values, exhibiting almost 100% change in resistance when subjected to a pressure of 400 mmHg and high sensitivity of 0.27 mmHg-1. After promising outcomes were obtained during static pressure measurement, the sensor was used for BP monitoring in humans. The sensor accurately traced the oscillometric waveform (OMW) for distinct systolic blood pressure (SBP) and diastolic blood pressure (DBP) combinations to cover a range of medical situations, including hypotension, standard or normal, and hypertension. The values of SBP, DBP, and MAP were derived from the sensor's output using the MAA technique, and the errors in these values concerning the simulator and the traditional BP monitor follow the universal AAMI/ESH/ISO protocols. Bland-Altman (B&A) correlation and scatter plots were used to compare the sensor's results and further validate the proposed sensor. The sensor showed the mean and standard deviation error in the SBP, DBP, and MBP of -0.2 ± 5.9, -0.5 ± 7, and -0.9 ± 4.7 mmHg when compared with the noninvasive blood pressure (NIBP) simulator. The pulse rate (PR) was also calculated from the same OMW for the specified value of 80 beats per minute (bpm) given by the simulator and reported a mean PR value of ∼81 bpm, close to the reference value. The findings show that the flexible resistive sensing device can accurately measure BP and replace the existing sensors of BP devices.

An Insight into the Development of Potential Antidiabetic Agents along with their Therapeutic Targets.

Diabetes is a metabolic disorder that has been reported to increase the mortality rate worldwide. About 40 million people across the globe suffer from diabetes, with people living in developing countries being affected the most due to this deadly disease. Although the therapeutic management of hyperglycaemia can treat diabetes, metabolic disorders associated with this disease are a greater challenge in its treatment. Hence, potential strategies to treat hyperglycaemia and its side effects are needed. In this review, we have summarized several therapeutic targets, like dipeptidyl peptidase-4 (DPP-4), glucagon receptor antagonists, glycogen phosphorylase or fructose-1,6- biphosphatase inhibitors, SGLT inhibitors, 11beta-HSD-1 inhibitors, glucocorticoids receptor antagonists, glucose-6-phosphatase and glycogen phosphorylase inhibitors. These targets can help in designing and developing novel antidiabetic agents.

Synthesis, molecular docking and biological evaluation of 1,2,4-oxadiazole based novel non-steroidal derivatives against prostate cancer.

Prostate cancer is one of the most prevalent cancers in men leading to second most death causing cancer in men. Despite the availability of multiple treatment still the prevalence is high for prostate cancer. Steroidal antagonists associated with poor bioavailability, side effects while non-steroidal antagonists show serious side effects like gynecomastia. Therefore, there is a need of potential candidate for the treatment of prostate cancer with better bioavailability, good therapeutic effect and minimal side effects. In the same context, we have designed the series, SP1-SP25 based 3-phenyl-5-styryl-1,2,4-oxadiazole as the core structure. We successfully synthesized all 25 molecules in this series and characterized them using 1H, 13C NMR, and mass spectroscopy. Subsequently, we conducted MTT assays using PC-3 cells and observed that all the compounds exhibited a dose-dependent decrease in cell viability. Notably, compounds SP04, SP16, and SP19 demonstrated a significant decrease in cell viability and exhibited potent activity compared to the other synthesized molecules and standard drug bicalutamide. Among them, SP04 emerged as the one of the most potent compounds with an IC50 value of 238.13 nM and an 89.99 % inhibition of PC-3 cells, compared to synthesized molecules and standard drug bicalutamide. Furthermore, we conducted ROS assays and androgen receptor inhibition assays using the potent compound SP04 and bicalutamide. The results indicated that SP04 increased ROS production and decreased androgen receptor expression dose-dependent manner. Additionally, we conducted a docking study to analyse the interaction patterns within the active site of the androgen receptor. ADMET analysis revealed that all the compounds exhibited favorable physicochemical properties and manageable toxicity profiles.

Accuracy of oscillometric-based blood pressure monitoring devices: impact of pulse volume, arrhythmia, and respiratory artifact.

An oscillometric waveform (OMW) envelope-based blood pressure (BP) monitoring device is widely used to monitor blood pressure and prevent hypertension and adverse cardiovascular events. At present, all primary care physicians and clinicians widely recommend oscillometric-based BP devices. The consumer selects the device based on their own decision, without knowing whether the device is validated or not, resulting in over- or under-treatment of hypertension. It is imperative that each device must comply with international protocols. In this study, we have investigated the accuracy of inflation and deflation-based oscillometric BP monitoring devices in the case of sinus rhythm (SR). Since different health conditions of the patient affect the oscillometric waveform, which can affect the device's accuracy, in such cases, many BP monitors are skeptical of succeeding in the norms of international protocols. Therefore, this study also aims to calculate the accuracy of these devices in various health conditions and measure the effect of pulse volume, arrhythmia, and respiratory artifact on it using a non-invasive blood pressure (NIBP) simulator. We found that the oscillometric BP devices failed to measure the correct blood pressure in several clinical conditions.

Phenotypic alteration by dengue virus serotype 2 delays neutrophil apoptosis and stimulates the release of prosurvival secretome with immunomodulatory functions.

Neutrophils are the most abundant granuloytes, are phenotypically heterogeneous, and exert detrimental or protective roles during antiviral response. Dengue virus has been reported to activate neutrophils. However, the effect of the dengue virus on the neutrophil phenotypes, survival, and release of inflammatory secretome is yet to be understood. Herein, we investigated the effect of dengue virus serotype 2 (DV-2) on effector functions of naïve neutrophils and studied the impact of its secretome on different immune cells. We found that DV-2 activates purified human neutrophils and causes a significant shift toward the CD16bright/CD62Ldim subtype in a multiplicity of infection and time-dependent manner. These phenotypically altered neutrophils show delayed apoptosis through nuclear factor κB and PI3K pathways and have decreased phagocytic capacity. Treatment of neutrophils with myeloperoxidase and PAD4 inhibitor before DV-2 incubation significantly reduced DV-2-induced double-stranded DNA release, suggesting that myeloperoxidase and PAD4 were involved at early stages for the neutrophil activation and double-stranded DNA release. We also report that DV-2-stimulated neutrophil secretome had a significant effect on viral infection, platelet activation, and naïve neutrophil survival via binding of tumor necrosis factor α to tumor necrosis factor receptor 1/2 receptors. Furthermore, incubation of endothelial cells with the DV-2-stimulated neutrophil secretome potentially inhibits proliferation and wound healing capacity and induces endothelial cell death, which can contribute to endothelial barrier dysfunction. In conclusion, the neutrophil-DV-2 interaction modulates the phenotype of neutrophils and the release of prosurvival and antiviral secretome that may act as a double-edged sword during dengue pathogenesis.

Covalent Organic Framework Impregnated with Silver and Copper Nanoparticles: An Advanced Approach for Catalytic Degradation of Organic Pollutants in Wastewater.

In this study, we introduce an economically viable and scalable process for developing a novel covalent organic framework (COF), which is a cross-linked polymer. The resulting material, TzTFB-COF, is successfully functionalized with silver and copper nanoparticles, which show high adequacy in the degradation of nitroaromatic compounds (NACs). For the synthesis of TzTFB-COF, s-tetrazine diamine (Tz) and 1,3,5-triformylbenzene (TFB) are chosen as building blocks, which exhibit a high density of nitrogen-containing sites. TzTFB-COF shows good chemical and thermal stability (>300 °C). For functionalization of TzTFB-COF with silver and copper nanoparticles, a solution infiltration technique is used. The composite materials, i.e., Ag@TzTFB-COF and Cu@TzTFB-COF, have been characterized using various spectroscopic and analytical techniques, which show high activity, high selectivity, and excellent chemical and thermal stability up to 350 °C. The silver and copper contents of Ag@TzTFB-COF and Cu@TzTFB-COF are determined to be 9.6 and 12.4 wt % by inductively coupled plasma optical emission spectrometer (ICP-OES). The catalytic efficiency of the synthesized Ag@TzTFB-COF and Cu@TzTFB-COF materials is assessed in the context of catalyzing the hydrogenation of NACs. Experimental results reveal a remarkable catalytic performance when conducted in an aqueous medium, and notably, the materials demonstrate substantial potential for reusability across multiple catalytic cycles. The determined parameters for the catalytic hydrogenation reaction, i.e., the rate constants and Gibbs free energies, are found to be 0.0185 s-1 and 9.878 kJ/mol for Ag@TzTFB-COF and 0.0219 s-1 and 9.615 kJ/mol for Cu@TzTFB-COF. Thus, the catalytic reaction exhibits characteristics of endothermic, endergonic, and nonspontaneous nature.

Evaluation of blood pressure using a flexible and wearable capacitive pressure sensor.

In recent times, the high demand for flexible and wearable pressure sensors to monitor human health, particularly for patients afflicted with hypertension or high blood pressure (BP), has captured the keen interest of researchers. Capacitance-based flexible sensing devices offer real-time metrics regarding vital physiological parameters of the human body, such as BP and pulse rate (PR), thereby enabling the identification of cardiovascular complications. In this regard, we have developed a capacitive pressure sensor using polydimethylsiloxane (PDMS) and deionized water (DIW) and improved its key parameters by adding baking powder to PDMS-DIW. The sensor demonstrated excellent performance in static pressure measurements with a sensitivity of 0.021 Pa-1, detection limit of 1 Pa, and response time of 100 ms. We further investigated its application in human BP monitoring. The sensor successfully captured the oscillometric waveform (OMW) for all 160 participants and demonstrated excellent performance in accurately measuring BP, meeting all criteria outlined as the universal standard when compared with the reference devices: OMRON BP device and the gold-standard mercury-based sphygmomanometer. Furthermore, the sensor accurately provided the PR and agreed well with the reference BP device. Therefore, the developed BP sensor can be a viable alternative to replace the pressure sensors in existing BP devices.

Anomalous Concentration Dependence of Viscosity: Hidden Role of Cross-Correlations in Aqueous Electrolyte Solutions.

The viscosity of aqueous electrolyte solutions exhibits well-known composition-dependent anomalies that show certain definitive trends and universal features. The viscosity of LiCl and NaCl solutions increases with concentration in a monotonic fashion, while solutions of KCl, RbCl, and CsCl exhibit a more complex behavior. Here, the viscosity first decreases and then increases with increasing concentration, with a rather broad minimum at intermediate concentrations (ca. 1-3 m). To unearth the origin of such puzzling behavior, we carried out detailed molecular-level analyses by interrogating the exact Green-Kubo expression of viscosity in terms of the stress-stress time correlation function (SS-TCF). The total SS-TCF can be decomposed into a collection of three self- and three cross-SS-TCFs arising from the three constituent components (water, cations, and anions). Mode coupling theory (MCT) analysis for the friction on ions and the viscosity of the solution suggests the possible importance of two-particle static and time-dependent cross-correlations between water and the ions. We calculate the viscosity and other dynamical properties for all five electrolyte (LiCl, NaCl, KCl, RbCl, and CsCl) solutions over a range of concentrations, using two models of water (SPC/E and TIP4P/2005). The total viscosity derives non-negligible contributions from all of the terms. The cross-correlations are found to be surprisingly large and seen to play a hidden role in the concentration dependence. However, the importance of cross-correlations is often not discussed. Our study leads to a theoretical understanding of the microscopic origin of the observed anomalies in the composition dependence of viscosity across all five electrolytes.