Ionic liquid supported chitosan-g-SPA as a biopolymer-based single ion conducting solid polymer electrolyte for energy storage devices.

This article discusses the preparation of different grades of single-ion conducting quasi-solid polymer electrolytes (q-SPE) material (Chit-g-SPA-IL) based on biopolymer (chitosan), polyacrylic acid and DBU-acetate (DBUH+ AcO-) ionic liquid. Chit-SPA-60 %-IL exhibited the highest conductivity within the range of 10-4 S/cm. TGA analysis demonstrated the stability of electrolytes up to a temperature of 120 °C. SEM-EDS analysis unveiled the porous nature of the electrolyte and even distribution of ions throughout the matrix. It exhibited an electrochemical stability window (EWS) of 2.53 V with significant current density and an ionic transference number (ITN) of ~99.9 %. The temperature-dependent conductivity established an Arrhenius-type conduction mechanism with an activation energy of 0.149 eV for ion movement within the electrolyte matrix. The AC conductivity analysis emphasized the time-temperature independence of the ionic conduction mechanism. Dielectric analysis highlighted the capacitive nature of the electrolyte, underlining its substantial capacitance, while modulus studies indicated minimal influence from the electrode-electrolyte interface. Chit-SPA-60 %-IL at 30 °C included a self-diffusion coefficient of 4.57 × 10-5 m2/s, ionic mobility of 1.75 × 10-3 m2/Vs, and drift ionic velocity of 0.44 m/s. These findings makes SPE as a promising candidate for sodium-ion-based energy storage devices.

Fabrication of Nanobioengineered Interfaces Utilizing Quaternary Nanocomposite for Highly Efficient and Selective Electrochemical Biosensing of Urea.

Nanobioengineered interfaces have gained attention owing to their small size and high surface area-to-volume ratio for utilization as a platform for highly selective and sensitive biosensing applications owing to the integration of biological molecules with engineered nanomaterials/nanocomposites. In this work, a novel Ag-complex, [(PPh3)2Ag(SCOf)]-based quaternary Ag-S-Zn-O nanocomposites (NCs), was synthesized through an environmentally-friendly process. The results revealed the formation of the NCs with an average crystallite size and particle size of 36.08 and 40.22 nm, respectively. In addition, this is the first study to utilize such NCs synthesized via a single-source precursor method, offering enhanced sensor performance due to their unique structural properties. Further, these NCs were used to fabricate a urease (Ur)/Ag-S-Zn-O NCs/ITO nanobioengineered electrode for precise and sensitive electrochemical biosensing of urea. The interfacial kinetic studies revealed quasi-reversible processes with high electron transfer rates and linear current responses, indicating efficient reaction dynamics. A high diffusion coefficient and low surface concentration suggested a fast diffusion-controlled process, affirming the electrode's potential for rapid and sensitive urea detection. The biosensor demonstrated notable sensing properties such as high sensitivity (12.56 µA mM-1 cm-2) and a low detection limit (0.54 mM). The fabricated bioelectrode was highly selective and reproducible and demonstrated stability for up to 60 days. These results validate the potential of this nanobioengineered interface for next-generation biosensing applications, paving the way for advanced point-of-care diagnostics and real-time health monitoring.

Heterotopic Ossification of the Achilles Tendon in a Patient with Type II Diabetes Mellitus: A Case Report and Comprehensive Management Overview.

Introduction: Heterotopic ossification of the Achilles tendon (HOTA) is a rare but consequential complication to an inflammatory event, often presenting challenges in diagnosis and management. Case Report: We report a case of a 42-year-old male with Type II diabetes mellitus, managed with Metformin, who presented with acute pain and swelling in the right ankle following a running activity. Clinical examination revealed tenderness and a visible swelling proximal to the calcaneum attachment of the tendon which was hard in consistency, and a positive Thompson test indicative of a potential Achilles tendon injury. Imaging, including X-ray and magnetic resonance imaging, confirmed a complete avulsion tear with cranial retraction of the torn tendon and heterotopic ossification seen proximal to the torn end of the tendon. Surgical intervention, employing a posterior paramedian approach under tourniquet control, involved tendon approximation using the Speed bridge technique, incision over the proximal tendon and removal of the ossified tendon, and repair of the incised tendon sheath. Postoperatively, the patient received a tailored medication regimen and was advised strict non-weight-bearing measures, wound management, and limb elevation. The patient was discharged in a stable condition. Conclusion: This case underscores the importance of early recognition and prompt surgical intervention in managing HOTA, particularly in patients with underlying risk factors. The presented surgical approach and postoperative management contribute to the evolving strategies for addressing this rare clinically significant condition.

Electronic and Atomic Structural Properties Associated with Enhanced Photodegradation Activity in Mo-Doped TiO2 Nanoparticles.

The efficacy and structural evolution of Mo-doped titania nanoparticles (MTNPs) as advanced photocatalysts for degrading methyl blue (MB) are investigated by X-ray absorption spectroscopy (XAS). The 3 wt % MTNP, characterized by uniform size and anatase structure, exhibits higher efficiency. The spectral analyses unveiled structural variations in the TiO6 octahedral structure and revealed an active site of the distorted square pyramidal structure symmetry (C4v). The in situ XAS spectra illustrate that MTNPs, particularly at 3 wt % doping, effectively enhanced the hole carriers in Ti 3d orbitals with a charge transfer to Mo 4d orbitals and impeded electron-hole pair merging, significantly enhancing the photodegradation under light illumination. This study deepens our understanding of the crucial role of Mo doping in optimizing TiO2 nanoparticle performance for efficient environmental remediation, showcasing the potential of MTNPs as sustainable photocatalytic materials.

Potent and Protease Resistant Azapeptide Agonists of the GLP-1 and GIP Receptors.

The gut-derived peptide hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) play important physiological roles. Stabilized agonists of the GLP-1 receptor (GLP-1R) and the GIP receptor (GIPR) for the management of diabetes and obesity have generated widespread enthusiasm and have become blockbuster drugs. These therapeutics are refractory to the action of dipeptidyl peptidase-4 (DPP4), that catalyzes rapid removal of the two N-terminal residues of the native peptides, in turn severely diminishing their activity profiles.  Here we report that a single atom change from carbon to nitrogen in the backbone of the entire peptide make them refractory to DPP4 action while still retaining full potency and efficacy at their respective receptors.  This was accomplished by use of aza-amino acids, that are bioisosteric replacements for a-amino acids that perturb the structural backbone and local side chain conformations.  Molecular dynamics simulations reveal that aza-amino acid can populate the same conformational space that GLP-1 adopts when bound to the GLP-1R. The insertion of an aza-amino acid at the second position from the N-terminus in semaglutide and in a dual agonist of GLP-1R and GIPR further demonstrates its capability as a viable alternative to current DPP4 resistance strategies while offering additional structural variety.

Association Between Vitamin D Deficiency and Tumor Characteristics in Breast Cancer Patients.

Introduction Breast cancer is the most frequent cancer among women worldwide, but there is little literature regarding the effects of vitamin D on breast cancer patients in the Indian population. Hence, this study was planned to determine the correlation between vitamin D deficiency and tumor characteristics in breast cancer patients. Methods This was a cross-sectional study conducted in a tertiary healthcare facility in central India among all newly diagnosed patients with breast carcinoma who had received primary surgery and pathological confirmation. We performed universal sampling and included 50 patients in the study. We excluded patients with insufficient histopathological reports, those unfit for surgery, and those with hepatic or renal failure, metabolic bone disease, malabsorption, or recent consumption of vitamin D (patients who had received oral vitamin D in the preceding two weeks, or vitamin D injection in the preceding six months). Results Among the 50 patients, 86% were vitamin D deficient, with a mean deficiency of 23.54. Vitamin D deficiency is most common in the age groups 41-50 years and >60 years, with the mean age group of 51.49 years. The left side is more involved than the right in vitamin D-deficient patients. Most patients were moderately and poorly differentiated, suggesting a significant association between vitamin D deficiency and tumor differentiation. Almost half the patients were estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (Her-2/neu) status negative with vitamin D deficiency. Vitamin D deficiency was highest in Her-2/neu amplified, luminal A, and B patients. The mean lymph node-positive participants was 4.04, and the mean number of lymph nodes extracted was 15.58 in vitamin D-deficient breast cancer patients. Conclusion The prevalence of low vitamin D status was high among breast cancer patients. There is an association between vitamin D deficiency and tumors with poor prognostic features. Low vitamin D levels were considered a risk factor for ER, PR, and Her-2/neu-negative tumors along with positive lymph node status in breast cancer patients. Vitamin D status is a modifiable risk factor for breast cancer. Thus, it is concluded from this study that vitamin D has a potential role in the prevention of breast cancer, it may reduce its aggressiveness, and its deficiency is associated with an increased risk of breast cancer.

Prolonged Activation of the GLP-1 Receptor via Covalent Capture.

The incretin gut hormone glucagon-like peptide-1 (GLP-1) has become a household name because of its ability to induce glucose-dependent insulin release with accompanying weight loss in patients. Indeed, derivatives of the peptide exert numerous pleiotropic actions that favorably affect other metabolic functions, and consequently, such compounds are being considered as treatments for a variety of ailments. The ability of native GLP-1 to function as a clinical drug is severely limited because of its short half-life in vivo. All of the beneficial effects of GLP-1 come from its agonism at the cognate receptor, GLP-1R. In our quest for long-lived activation of the receptor, we hypothesized that an agonist that had the ability to covalently cross-link with GLP-1R would prove useful. We here report the structure-guided design of peptide analogues containing an electrophilic warhead that could be covalently captured by a resident native nucleophile on the receptor. The compounds were evaluated using washout experiments, and resistance to such washing serves as an index of prolonged activation and covalent capture, which we use to tabulate longevity and robust long-lived GLP-1R agonism. The addition of SulF (cross-linkable warhead), an N-terminal trifluoroethyl group (for protease protection), and a C18 diacid lipid (protractor) all contributed to the increased wash resistance of GLP-1. The most effective compound based on the wash resistance metric, C2K26DAC18_K34SulF, has all three elements outlined and may serve as a blueprint and a proof-of-concept scaffold for the design of clinically useful molecules.

Molecular design of peptide therapeutics via N-terminal modification.

Glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide, and glucagon are three naturally occurring peptide hormones that mediate glucoregulation. Several agonists representing appropriately modified native ligands have been developed to maximize metabolic benefits with reduced side-effects and many have entered the clinic as type 2 diabetes and obesity therapeutics. In this work, we describe strategies for improving the stability of the peptide ligands by making them refractory to dipeptidyl peptidase-4 catalyzed hydrolysis and inactivation. We describe a series of alkylations with variations in size, shape, charge, polarity, and stereochemistry that are able to engender full activity at the receptor(s) while simultaneously resisting enzyme-mediated degradation. Utilizing this strategy, we offer a novel method of modulating receptor activity and fine-tuning pharmacology without a change in peptide sequence.

The mRNA-capping enzyme localizes to stress granules in the cytoplasm and maintains cap homeostasis of target mRNAs.

The model of RNA stability has undergone a transformative shift with the revelation of a cytoplasmic capping activity that means a subset of transcripts are recapped autonomously of their nuclear counterparts. The present study demonstrates nucleo-cytoplasmic shuttling of the mRNA-capping enzyme (CE, also known as RNA guanylyltransferase and 5'-phosphatase; RNGTT), traditionally acknowledged for its nuclear localization and functions, elucidating its contribution to cytoplasmic capping activities. A unique nuclear export sequence in CE mediates XPO1-dependent nuclear export of CE. Notably, during sodium arsenite-induced oxidative stress, cytoplasmic CE (cCE) congregates within stress granules (SGs). Through an integrated approach involving molecular docking and subsequent co-immunoprecipitation, we identify eIF3b, a constituent of SGs, as an interactive associate of CE, implying that it has a potential role in guiding cCE to SGs. We measured the cap status of specific mRNA transcripts from U2OS cells that were non-stressed, stressed and recovered from stress, which indicated that cCE-target transcripts lost their caps during stress but remarkably regained cap stability during the recovery phase. This comprehensive study thus uncovers a novel facet of cytoplasmic CE, which facilitates cellular recovery from stress by maintaining cap homeostasis of target mRNAs.