Coronavirus disease (COVID-19) is an infectious disease that has posed a global health challenge caused by the SARS-CoV-2 virus. Early management and diagnosis of SARS-CoV-2 are crucial for the ...timely treatment, traceability, and reduction of viral spread. We have developed a rapid method using a Graphene-based Field-Effect Transistor (Gr-FET) for the ultrasensitive detection of SARS-CoV-2 Spike S1 antigen (S1-Ag). The in-house developed antispike S1 antibody (S1-Ab) was covalently immobilized on the surface of a carboxy functionalized graphene channel using carbodiimide chemistry. Ultraviolet–visible spectroscopy, Fourier-Transform Infrared Spectroscopy, X-ray Photoelectron Spectroscopy (XPS), Atomic Force Microscopy (AFM), Optical Microscopy, Raman Spectroscopy, Scanning Electron Microscopy (SEM), Enzyme-Linked Immunosorbent Assays (ELISA), and device stability studies were conducted to characterize the bioconjugation and fabrication process of Gr-FET. In addition, the electrical response of the device was evaluated by monitoring the change in resistance caused by Ag–Ab interaction in real time. For S1-Ag, our Gr-FET devices were tested in the range of 1 fM to 1 μM with a limit of detection of 10 fM in the standard buffer. The fabricated devices are highly sensitive, specific, and capable of detecting low levels of S1-Ag.
Abstract
Objectives
Because of the rise in antimicrobial resistance, an inexpensive, diet-based treatment against Helicobacter pylori infection would be of great interest. The present study was ...performed to assess the in vitro effects of ellagic acid against clinical H. pylori strains that were resistant to antibiotics used for therapy and also to observe the morphological structure following treatment with ellagic acid. The effectiveness of ellagic acid in eradicating H. pylori infection in a murine (C57BL/6) infection model, one of the standard inbred mouse lines often used for experimental infection, was also assessed.
Methods
A total of 55 strains were screened. The agar dilution method was used to determine the susceptibility of isolates to test compounds. Transmission electron microscopy was used to observe the morphology following treatment with ellagic acid. The antibacterial activity of ellagic acid in an H. pylori SS1-infected mouse model and its effect on gastric mucosal injury were determined by histology and PCR.
Results
Ellagic acid inhibited the growth of all 55 of the H. pylori strains tested. The MIC of ellagic acid ranged from 5 to 30 mg/L, showing its bactericidal properties in vitro. Ellagic acid also demonstrated anti-H. pylori efficacy in eradication of this organism in an in vivo model, as well as restitution and repair of H. pylori-induced gastric mucosal damage.
Conclusions
The present study paves the way for the preventive and therapeutic use of ellagic acid against H. pylori infection and, thus, ellagic acid can be considered a promising antibacterial agent against H. pylori-associated gastroduodenal diseases in humans.
In the intricate landscape of Traumatic Brain Injury (TBI), the management of TBI remains a challenging task due to the extremely complex pathophysiological conditions and excessive release of ...reactive oxygen species (ROS) at the injury site and the limited regenerative capacities of the central nervous system (CNS). Existing pharmaceutical interventions are limited in their ability to efficiently cross the blood-brain barrier (BBB) and expeditiously target areas of brain inflammation. In response to these challenges herein, we designed novel mussel inspired polydopamine (PDA)-coated mesoporous silica nanoparticles (PDA-AMSNs) with excellent antioxidative ability to deliver a new potential therapeutic GSK-3β inhibitor lead small molecule abbreviated as Neuro Chemical Modulator (NCM) at the TBI site using a neuroprotective peptide hydrogel (PANAP). PDA-AMSNs loaded with NCM (i.e., PDA-AMSN-D) into the matrix of PANAP were injected into the damaged area in an in vivo cryogenic brain injury model (CBI). This approach is specifically built while keeping the logic AND gate circuit as the primary focus. Where NCM and PDA-AMSNs act as two input signals and neurological functional recovery as a single output. Therapeutically, PDA-AMSN-D significantly decreased infarct volume, enhanced neurogenesis, rejuvenated BBB senescence, and accelerated neurological function recovery in a CBI.In the intricate landscape of Traumatic Brain Injury (TBI), the management of TBI remains a challenging task due to the extremely complex pathophysiological conditions and excessive release of reactive oxygen species (ROS) at the injury site and the limited regenerative capacities of the central nervous system (CNS). Existing pharmaceutical interventions are limited in their ability to efficiently cross the blood-brain barrier (BBB) and expeditiously target areas of brain inflammation. In response to these challenges herein, we designed novel mussel inspired polydopamine (PDA)-coated mesoporous silica nanoparticles (PDA-AMSNs) with excellent antioxidative ability to deliver a new potential therapeutic GSK-3β inhibitor lead small molecule abbreviated as Neuro Chemical Modulator (NCM) at the TBI site using a neuroprotective peptide hydrogel (PANAP). PDA-AMSNs loaded with NCM (i.e., PDA-AMSN-D) into the matrix of PANAP were injected into the damaged area in an in vivo cryogenic brain injury model (CBI). This approach is specifically built while keeping the logic AND gate circuit as the primary focus. Where NCM and PDA-AMSNs act as two input signals and neurological functional recovery as a single output. Therapeutically, PDA-AMSN-D significantly decreased infarct volume, enhanced neurogenesis, rejuvenated BBB senescence, and accelerated neurological function recovery in a CBI.
Experimental results for optically controlled electron-transfer reaction kinetics (ETRK) and nonequilibrium solvation dynamics (NESD) of Coumarin 480 in DMPC vesicle show their dependence on ...excitation wavelength λex. However, the celebrated Marcus theory and linear-response-theory-based approaches for ETRK and NESD, respectively, predict both of the processes to be independent of λex. The above said lacuna in these theories prompted us to develop a novel theory in 1D space, where the effect of innumerable Franck–Condon states is included through λex. The present theory not only sheds light on the origin of failure of the existing theories but also gives the correct trend for the effect of λex on ETRK and NESD. More importantly, the calculated results of NESD are in excellent agreement with the experimental results for different values of λex. The new theory will therefore advance the knowledge of scientific community on the dynamics of photoinduced nonequilibrium processes.
Open reduction and internal fixation (ORIF) of mandibular condylar fracture with a three dimensional stabilization has been a controversial topic in oral and maxillofacial surgery. Miniplates and ...many 3D plates have been used till now for fixation of condylar fracture and delta plate is one of them. Present literature has less evidence about which one is superior over another. We have tried to evaluate the clinical performance of the delta miniplate in this study. A total of 10 patients presenting mandibular condylar fracture were treated by ORIF using delta miniplate. Dimensional details were measured of 10 dry human mandibles. At the end of 1-year follow-up period, all patients had satisfactory results, both clinically and radiologically. Delta plate showed better stability in the condylar region and less complication associated with plating system.
Selective laser melting (SLM) is a widely applied process in the metal additive manufacturing industry. The microstructure and mechanical properties of SLM products can be significantly affected by ...the SLM process parameters. In the present work, optimization of SLM process parameters was performed using the Taguchi optimization method for 316L austenitic stainless steel. Laser power, scan speed, layer thickness, and hatch spacing were selected as the controllable process parameters and relative density, ultimate tensile strength, and elongation as the performance evaluation characteristics. The S/N ratio analysis determined the optimum process parameters of the SLM process in 316L stainless steel. ANOVA analysis predicted that scan speed significantly affected the relative density with a 42.38% contribution and laser power showed contributions of 31.17% and 45.67% for ultimate tensile strength and elongation, respectively. The linear regression model was developed for relative density, ultimate tensile strength, and elongation with the coefficient of determination of 90.17%, 93.06%, and 81.53%, respectively.
Cholestatic disorders are a significant cause of morbidity and mortality in infants. Characterization of these disorders and differentiating biliary atresia (BA) from other causes of intrahepatic ...cholestasis is an age-old problem.
To study the spectrum of different infantile cholestatic disorders in our population, to differentiate BA from other causes of neonatal cholestasis (NC) on a liver biopsy, and validation of the available scoring system for the characterization of these disorders.
This is an observational cross-sectional study performed over a period of 3 years between 2018 and 2021, done on neonates and infants presenting with cholestatic jaundice. The changes on liver biopsy were evaluated by different histological parameters and available scoring systems to differentiate BA from non-BA causes. Correlation with clinical, biochemical, and imaging findings was done in all cases.
This study included 87 cases of NC, of which BA comprised 28 cases (32%), whereas idiopathic neonatal hepatitis (INH) comprised only 12 cases (14%). Portal neutrophilic inflammation (P = 0.000053), ductal cholestasis (P < 0.001), neoductular bile plugs (P < 0.001) and bile ductular proliferation (P < 0.0001) were significantly more in BA, whereas lobular lymphocytic inflammation (P = 0.001) and giant cell transformation of hepatocytes (P = 0.0024) were more frequent in the non-BA group. Using the Lee and Looi scoring system, a histologic score ≥7 was helpful in identifying BA with 85.7% sensitivity, 92.6% specificity, and 90.6% accuracy.
BA is the commonest cause of NC in neonates, whereas the frequency of INH is declining. Detailed histomorphologic analysis of liver biopsy, aided with IHC, is the cornerstone for the diagnosis of these disorders.
Growth factors play a pivotal role in orchestrating cellular growth and division by binding to specific cell surface receptors. Dysregulation of growth factor production or activity can contribute to ...the uncontrolled cell proliferation observed in cancer. Peptide-based nanoformulations (PNFs) have emerged as promising therapeutic strategies for growth factor-deficient cancers. PNFs offer multifaceted capabilities including targeted delivery, imaging modalities, combination therapies, resistance modulation, and personalized medicine approaches. Nevertheless, several challenges remain, including limited specificity, stability, pharmacokinetics, tissue penetration, toxicity, and immunogenicity. To address these challenges and optimize PNFs for clinical translation, in-depth investigations are warranted. Future research should focus on elucidating the intricate interplay between peptides and nanoparticles, developing robust spectroscopic and computational methodologies, and establishing a comprehensive understanding of the structure-activity relationship governing peptide-nanoparticle interactions. Bridging these knowledge gaps will propel the translation of peptide-nanoparticle therapies from bench to bedside. While a few peptide-nanoparticle drugs have obtained FDA approval for cancer treatment, the integration of nanostructured platforms with peptide-based medications holds tremendous potential to expedite the implementation of innovative anticancer interventions. Therefore, growth factor-deficient cancers present both challenges and opportunities for targeted therapeutic interventions, with peptide-based nanoformulations positioned as a promising avenue. Nonetheless, concerted research and development endeavors are essential to optimize the specificity, stability, and safety profiles of PNFs, thereby advancing the field of peptide-based nanotherapeutics in the realm of oncology research.
The graphical abstract concerns theranostic applications of peptide-based nanoparticles in growth factor defective cancers. They can carry drugs or gene-silencing molecules to the cancer cells as cargo, bind to specific receptors on the cancer cells and enter them. The particles then release their cargo inside the cells and kill them. This approach is claimed to be more selective, flexible, and effective than traditional therapies, subject to more clinical data from large-scale human trials. Efforts are more towards increasing the scalability of this technology. Display omitted
Introduction: To date, a few research studies have reported the significance of synaptonemal complex protein 3 (SYCP3) gene mutation in breast cancer. The present study aims to identify SYCP3 gene ...mutation in the case of breast cancer in female Albino mice and to assess the interaction of mutated SYCP3 protein with the drug methotrexate (MTX).
Materials and Methods: To induce breast cancer in female Albino mice, the carcinogen 7, 12-Dimethylbenz (a) anthracene was used. The blood samples were collected from mice that developed breast cancer and a polymeric chain reaction was performed to check the mutation in the SYCP3 gene with a specific primer. Thereafter, whole genome sequencing was performed, which was further validated by referring to online bioinformatics databases and tools.
Results: After performing whole genome sequencing and translation, the normal SYCP3 sequence was compared with the mutated one, where a frameshift mutation was observed in which 1 bp was deleted at position (643delA) (Al ─A that codes for ILE at position 197 (ILE ─I in protein sequence. The free binding energy released by the interaction of MTX with the mutated SYCP3 protein (MET, GLU, GLN, GLU, and ILE) was lower (−3.09 Kcal/mol) than that of the interaction of normal SYCP3 protein. Therefore, the mutated SYCP3 and MTX interaction can be considered the best molecular docking interaction.
Conclusion: The present study is imperative to recognize a potential therapeutic agent to cure breast cancer. It ultimately paves the way to modify the existing line of treatment for different pathological conditions of breast cancer and promote personalized medicine.
Binary van der Waals heterostructures of graphene (Gr) and transition metal dichalcogenide (TMDC) have evolved as a promising candidate for photodetection with very high responsivity due to the ...separation of photo‐excited electron–hole pairs across the interface. The spectral range of optoelectronic response in such hybrids has so far been limited by the optical bandgap of the light absorbing TMDC layer. Here, the bidirectionality of interlayer charge transfer is utilized for detecting sub‐band gap photons in Gr‐TMDC heterostructures. A Gr/MoSe2 heterostructure sequentially driven by visible and near infra‐red (NIR) photons is employed, to demonstrate that NIR induced back transfer of charge allows fast and repeatable detection of the low energy photons (less than the optical band gap of the TMDC layer). This mechanism provides photoresponsivity as high as ≈3000 A W−1 close to the communication wavelength. The experiment provides a new strategy for achieving highly efficient photodetection over a broad range of energies beyond the spectral bandgap with the 2D semiconductor family.
This work exploits the bidirectionality of interlayer charge transfer in graphene‐transition metal dichalcogenide heterostructures and demonstrates a reverse charge transfer mechanism to detect sub‐bandgap NIR photons. This novel mechanism allows fast and repeatable detection of low energy photons (<Eg) with a photoresponsivity as high as ≈3000 A W−1 close to the communication wavelength.