Medullary nephrocalcinois and primary hyperaldosteronism - A rare and under recognised association.

ABSTRACT: Medullary nephrocalcinosis is an uncommon manifestation of primary hyperaldosteronism (PHA) and the exact etiology of this association is still debated. Here we report three cases of PHA with medullary nephrocalcinosis and how medullary nephrocalcinosis in one patient led to misdiagnosis as renal tubular acidosis (RTA). Although PHA and RTA can share overlapping symptoms, careful evaluation of clinical presentation, biochemical tests, and imaging studies are essential to differentiate between the two conditions and ensure appropriate management. Also, awareness of this uncommon manifestation of PHA is essential to avoid misdiagnosis as tubulopathy, as this may delay the treatment.

Reinforced Immediate Dentin Sealing vs Conventional Immediate Dentin Sealing on Adhesive Behavior of Indirect Restorations: A Systematic Review.

AIM: The aim of this systematic review is to compare the bonding performance of indirect restoration with the reinforced immediate dentin sealing (IDS) method as opposed to the conventional IDS method. MATERIALS AND METHODS: A literature search was conducted in PubMed, Cochrane, and EBSCOHost up to January 31st 2022, accompanied by a hand search in Google Scholar. Inclusion criteria involved studies comparing conventional IDS and reinforced IDS protocol and evaluating various parameters influencing the bonding performance, such as type of indirect restoration, etching protocol, cavity design, tooth surface preparation, method of oral cavity simulation, and processing after luting. The quality of six included studies was appraised using CRIS guidelines. RESULTS: A total of 29 publications was identified, and 6 of them fulfilled the inclusion criteria. All of the included studies were in vitro studies. The predetermined data were independently extracted and evaluated by four reviewers. It was observed that most of the studies showed an improvement in bond strength with reinforced IDS when compared with conventional IDS. Also, etch-and-rinse and 2-step self-etch adhesive protocols have shown better bonding performance than universal adhesive systems. CONCLUSION: Reinforced IDS has similar or better bond strength to that of conventional IDS strategies. The need for prospective studies is highlighted. The future clinical studies for immediate dentin sealing ought to be reported in a uniform and methodological way. CLINICAL SIGNIFICANCE: Application of an additional layer of low-viscosity resin composite provides a thicker adhesive layer, prevents re-exposure of dentin during the final restoration, and allows a smoother preparation in lesser clinical chair time and eliminates any possible undercuts. Thus, reinforced IDS has shown to result in better preservation of the dentinal seal than IDS technique.

Conversion of RNA Aptamer into Modified DNA Aptamers Provides for Prolonged Stability and Enhanced Antitumor Activity.

Aptamers, synthetic single-strand oligonucleotides that are similar in function to antibodies, are promising as therapeutics because of their minimal side effects. However, the stability and bioavailability of the aptamers pose a challenge. We developed aptamers converted from RNA aptamer to modified DNA aptamers that target phospho-AXL with improved stability and bioavailability. On the basis of the comparative analysis of a library of 17 converted modified DNA aptamers, we selected aptamer candidates, GLB-G25 and GLB-A04, that exhibited the highest bioavailability, stability, and robust antitumor effect in in vitro experiments. Backbone modifications such as thiophosphate or dithiophosphate and a covalent modification of the 5'-end of the aptamer with polyethylene glycol optimized the pharmacokinetic properties, improved the stability of the aptamers in vivo by reducing nuclease hydrolysis and renal clearance, and achieved high and sustained inhibition of AXL at a very low dose. Treatment with these modified aptamers in ovarian cancer orthotopic mouse models significantly reduced tumor growth and the number of metastases. This effective silencing of the phospho-AXL target thus demonstrated that aptamer specificity and bioavailability can be improved by the chemical modification of existing aptamers for phospho-AXL. These results lay the foundation for the translation of these aptamer candidates and companion biomarkers to the clinic.

Biochemical and phylogenetic networks-I: hypertrees and corona products.

We have obtained graph-theoretically based topological indices for the characterization of certain graph theoretical networks of biochemical interest. We have derived certain distance, degree and eccentricity based topological indices for various k-level hypertrees and corona product of hypertrees. We have also pointed out errors in a previous study. The validity of our results is supported by computer codes for the respective indices. Several biochemical applications are pointed out.

Biochemical and phylogenetic networks-II: X-trees and phylogenetic trees.

The present study, which is a continuation of the previous paper, augments a recent work on the use of phylogenetic networks. We develop techniques to characterize the topology of various X-trees and binary trees of biological and phylogenetic interests. We have obtained the results for various k-level X-trees and phylogenetic networks with variants of Zagreb, Szeged, Padmakar-Ivan, Schultz and Atom Bond Connectivity topological indices.

Thrombolysis beyond 4.5 h in Acute Ischemic Stroke.

PURPOSE OF REVIEW: The purpose of this article is to review the current approaches using neuroimaging techniques to expand eligibility for intravenous thrombolytic therapy in acute ischemic stroke patients with stroke of unknown symptom onset. RECENT FINDINGS: In recent years, several randomized, placebo-controlled trials have shown neuroimaging-guided approaches to be feasible in determining eligibility for alteplase beyond 4.5 h from last known well, and efficacious for reducing disability. DWI-FLAIR mismatch on MRI is an effective tool to identify stroke lesions less than 4.5 h in onset in patients with stroke of unknown symptom onset. Additionally, an automated perfusion-based approach, assessing for a disproportionate amount of salvageable tissue, is effective in identifying patients likely to benefit from late window alteplase treatment. In patients with stroke of unknown symptom onset, an individualized approach using neuroimaging to determine time of stroke onset or presence of salvageable brain tissue is feasible in the acute setting and associated with improved long-term outcomes.

Socioeconomic Risk Factors for Poor Outcomes of Developmental Dysplasia of the Hip.

OBJECTIVE: To examine the relationship between socioeconomic factors and outcomes of developmental dysplasia of the hip (DDH). STUDY DESIGN: A retrospective review of patients with DDH at a tertiary pediatric hospital from 2003 to 2012 with 2 years minimum follow-up was conducted. The relationship between socioeconomic factors with late presentation, treatment, and outcomes was examined. Socioeconomic factors included insurance status, language, and ethnicity. RESULTS: In total, 188 patients met criteria. Patients with late presentations were more likely to be Hispanic (P = .02). However, public insurance and a non-English language were not associated with late presentation. Hispanic patients (P = .01) and patients with a non-English language (P = .01) had a lower nonoperative treatment success rate. Hispanic patients had more surgical procedures performed than non-Hispanic patients (P = .04). Patients with range of motion limitations were more likely to have public insurance (P = .05) and be Hispanic (P = .04). On multiple logistic regression analysis controlling for late presentation, patients with public insurance had increased odds of range of motion limitations (OR 2.22, P = .04). Patients with public insurance (OR 0.44, P = .04), a non-English primary language (OR 0.30, P < .01), and Hispanic ethnicity (OR 0.37, P = .01) had decreased odds of successful nonoperative treatment. CONCLUSIONS: Public insurance, a non-English language, and Hispanic ethnicity are risk factors for inferior outcomes for DDH. When controlling for late presentation, these were significant risk factors for nonoperative treatment failure.

Upper extremity conversion disorder in children.

BACKGROUND: Conversion disorder in children presents a challenge to orthopedic surgeons. The condition is frequently associated with unnecessary diagnostic tests, treatments, and cost. The purpose of this study was to report a series of children with upper extremity conversion disorder to raise awareness for this uncommon condition and to assist with its diagnosis and management. METHODS: A retrospective review was conducted of 4 pediatric patients with upper extremity conversion disorder at a tertiary pediatric hospital from 2015 to 2017. Medical records were reviewed for patient demographics, including psychiatric history, clinical findings, diagnostic studies, treatment, and cost of care. RESULTS: Patients presented with upper extremity muscle stiffness, unremitting dysmorphic muscle spasms, weakness, pain, very limited shoulder range of motion, and complaints of recurrent shoulder dislocations. All patients had been evaluated by multiple specialists and had an extensive prior diagnostic workup that was inconclusive. Two patients had a history of prior psychiatric illness and suicidal ideation, and all patients expressed despair and depression. All patients had normal physical examination findings under anesthesia. Two patients with muscle stiffness were treated with botulism injections and improved their shoulder range of motion. The average total charge for care since presentation was $42,729. CONCLUSIONS: Conversion disorder should be considered in patients with an extensive prior diagnostic workup, deficits inconsistent with anatomic patterns or imaging findings, and a history of prior psychiatric illness. Examination under anesthesia is a successful diagnostic approach in children with suspected conversion disorder.

The Incidence of Pin Tract Infections and Septic Arthritis in Percutaneous Distal Femur Pinning.

BACKGROUND: Retrograde percutaneous pinning often involves intra-articular pin placement. Classic teaching has cautioned about the risk of septic arthritis with intra-articular pins, although an incidence has not been reported for this complication. The purpose of this study was to determine the incidence of pin tract infections and septic arthritis following retrograde percutaneous pinning of the distal femur. METHODS: A retrospective review identified patients who underwent retrograde percutaneous pinning of the distal femur for osteotomy or physeal fracture fixation at a tertiary pediatric hospital from 2006 to 2017 and had at least 3 months follow-up. The incidence of pin site infections and septic arthritis was determined. RESULTS: In total, 163 patients met criteria, 142 patients with osteotomies and 21 with physeal fractures. The mean pin duration was 33.2±9.0 days (range: 18 to 68 d). Pin duration of ≥30 days was associated with an increased rate of pin tract infections (11.2% vs. 1.4%, P=0.01). The incidence of pin tract infections was 6.7% (11/163), including 9.5% (2/21) in those with fractures and 6.3% (9/142) following osteotomy (P=0.64). There were no cases of septic arthritis. Of the 11 patients with pin tract infections, 9 were treated successfully with oral antibiotics and 2 patients (1.2%) underwent surgical intervention for infection. Treatment of pin infections with oral antibiotics alone was successful in all 7 patients whose pins were removed within 35 days of surgery, but in only 2 of 4 whose pins were removed later (P=0.11). Of the 2 patients who required irrigation and debridement, one had a superficial pin site infection and retained subcutaneous pin and the other had a pin tract abscess and osteomyelitis at the osteotomy site. CONCLUSIONS: Of 163 patients who underwent retrograde percutaneous pinning of the distal femur, no patient developed septic arthritis and the incidence of pin site infections was 6.7% (11/163). Intra-articular retrograde percutaneous pinning of the distal femur is a safe technique with a low risk of septic arthritis. LEVEL OF EVIDENCE: Level III-case-control study.

The soluble ligand Y box-1 activates Notch3 receptor by binding to epidermal growth factor like repeats 20-23.

The transduction of signal by the Notch receptors to the intracellular domain is highly regulated and relies on binding of the ligands to the Epidermal growth factor Like Repeats (ELRs) of receptor's extracellular domain. Both canonical and non-canonical ligands are known to interact with different ELRs and activate Notch receptors. The aim of this study was to investigate the interaction of a soluble non-canonical ligand, Y box-1 (Yb-1) with Notch3 receptor ELRs. Polyclonal antibodies were employed as novel tools to identify the binding site of this ligand. Using various ligand binding and signaling assays, soluble Yb-1 was found to interact specifically with the Notch3 receptor, but not with Notch1. The ELRs 17-24 of Notch3 were identified as the binding site for Yb-1. Further, Yb-1 and Notch3 ELRs 17-24 structures were modelled and the Yb-1-Notch3 interaction interface was predicted to be Notch3 ELRs 20-23. Binding of the Yb-1 with Notch3 ELRs different from those reported for canonical DSL ligands also transduced the signal to the intracellular domain through the negative regulatory region. In conclusion, study highlights the importance of molecular modifications in different Notch3 ELRs for the transduction of signal to the negative regulatory region.

Foam Padding in Postoperative Lower Extremity Casting: An Inexpensive Way to Protect Patients.

BACKGROUND: Although postoperative cast immobilization is routinely used in children, it is not without complications. Few studies have focused on interventions to decrease their frequency. The purpose of this study was to determine if foam padding in postoperative lower extremity casts decreased the rate of cast complications. METHODS: A retrospective review of patients who underwent lower extremity casting after elective surgery at a tertiary pediatric hospital from 2006 to 2013 was conducted. Postoperative casts were classified by type (A-frame, short leg, long leg, spica) and the presence of foam. Charts were reviewed for skin complications, cast splits for apparent neurovascular deficits, cast splits for patient complaints, unplanned outpatient returns for cast-related issues, and compartment syndrome. RESULTS: In total, 920 patients with 2,481 casts were included. In total, 612 (24.7%) casts had foam placed during casting. The incidence of skin complications was significantly lower in A-frame casts with foam (4.5%, 5/112) than without (13.4%, 11/82) (P=0.03) and long leg casts with foam (0.9%, 2/225) than without (4.3%, 19/444) (P=0.02). Patients with static encephalopathy casted with foam had a lower incidence of skin complications (0.7%, 2/279) than those without (3.6%, 22/615) (P=0.01). There was no difference in the overall incidence of skin complications in casts with and without foam (P=0.44), short leg casts (P=0.37), and spica casts (P=0.34). Patients with skin complications (20.3±7.1 kg/m) had a higher body mass index than those without (18.9±5.4 kg/m) (P=0.04). Postoperative A-frame casts with foam (0.0%, 0/112) were split less often for apparent neurovascular deficits than those without foam (4.5%, 3/67) (P=0.05). The cast split rates for apparent neurovascular deficits in casts with and without foam (P=0.58), long leg casts (P=0.67), short leg casts (P=0.63), and spica casts (P=1.0) were comparable. CONCLUSIONS: The use of foam in postoperative lower extremity casting is an effective intervention to reduce the incidence of skin complications in patients with static encephalopathy, in an A-frame cast, or in a long leg cast. LEVEL OF EVIDENCE: Level III-retrospective comparative study.

Novel anti IGFBP2 single chain variable fragment inhibits glioma cell migration and invasion.

Insulin like growth factor binding protein 2 (IGFBP2) is highly up regulated in glioblastoma (GBM) tissues and has been one of the prognostic indicators. There are compelling evidences suggesting important roles for IGFBP2 in glioma cell proliferation, migration and invasion. Extracellular IGFBP2 through its carboxy terminal arginine glycine aspartate (RGD) motif can bind to cell surface α5ß1 integrins and activate pathways downstream to integrin signaling. This IGFBP2 activated integrin signaling is known to play a crucial role in IGFBP2 mediated invasion of glioma cells. Hence a molecular inhibitor of carboxy terminal domain of IGFBP2 which can inhibit IGFBP2-cell surface interaction is of great therapeutic importance. In an attempt to develop molecular inhibitors of IGFBP2, we screened single chain variable fragment (scFv) phage display libraries, Tomlinson I (Library size 1.47 × 10(8)) and Tomlinson J (Library size 1.37 × 10(8)) using human recombinant IGFBP2. After screening we obtained three IGFBP2 specific binders out of which one scFv B7J showed better binding to IGFBP2 at its carboxy terminal domain, blocked IGFBP2-cell surface association, reduced activity of matrix metalloprotease 2 in the conditioned medium of glioma cells and inhibited IGFBP2 induced migration and invasion of glioma cells. We demonstrate for the first time that in vitro inhibition of extracellular IGFBP2 activity by using human scFv results in significant reduction of glioma cell migration and invasion. Therefore, the inhibition of IGFBP2 can serve as a potential therapeutic strategy in the management of GBM.

Antibodies against the extracellular domain of human Notch1 receptor reveal the critical role of epidermal-growth-factor-like repeats 25-26 in ligand binding and receptor activation.

The Notch signalling pathway is implicated in a wide variety of cellular processes throughout metazoan development. Although the downstream mechanism of Notch signalling has been extensively studied, the details of its ligand-mediated receptor activation are not clearly understood. Although the role of Notch ELRs [EGF (epidermal growth factor)-like-repeats] 11-12 in ligand binding is known, recent studies have suggested interactions within different ELRs of the Notch receptor whose significance remains to be understood. Here, we report critical inter-domain interactions between human Notch1 ELRs 21-30 and the ELRs 11-15 that are modulated by calcium. Surface plasmon resonance analysis revealed that the interaction between ELRs 21-30 and ELRs 11-15 is ~10-fold stronger than that between ELRs 11-15 and the ligands. Although there was no interaction between Notch1 ELRs 21-30 and the ligands in vitro, addition of pre-clustered Jagged1Fc resulted in the dissociation of the preformed complex between ELRs 21-30 and 11-15, suggesting that inter-domain interactions compete for ligand binding. Furthermore, the antibodies against ELRs 21-30 inhibited ligand binding to the full-length Notch1 and subsequent receptor activation, with the antibodies against ELRs 25-26 being the most effective. These results suggest that the ELRs 25-26 represent a cryptic ligand-binding site which becomes exposed only upon the presence of the ligand. Thus, using specific antibodies against various domains of the Notch1 receptor, we demonstrate that, although ELRs 11-12 are the principal ligand-binding site, the ELRs 25-26 serve as a secondary binding site and play an important role in receptor activation.

Comparative evaluation of the marginal fit of computer-aided design-computer aided manufacturing fabricated crowns from direct and indirect digital impression - A systematic review.

The accuracy of the digital impression method is responsible for fabricating crowns with adequate marginal fit which in turn determines the postendodontic prognosis. This systematic review was undertaken to identify the influence of the two digital impression techniques in producing full coverage crowns with better marginal fit. This systematic review was conducted according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. A detailed search was done in electronic databases (PubMed, EBSCOhost, LILACS, Cochrane) along with hand searches of reference articles. In vivo crossover studies comparing the marginal fit of the computer-aided design-computer-aided manufacturing (CAD-CAM) fabricated crowns from direct and indirect digital impressions published from inception till July 2023 were included in this review. The quality assessment of the included articles was done based on a modified Cochrane collaboration tool for crossover studies. A total of 280 articles were identified, after duplicate removal, title and abstract screening, and full-text evaluation, 7 articles were included in this systematic review. The overall quality of evidence is moderate. The CAD-CAM crowns fabricated from direct digital impressions exhibited a better marginal fit than those crowns fabricated by indirect digital impressions. The overall quality of evidence is moderate. Further clinical studies has to be conducted for evaluating the latest technologies towards achieving the misfit of zero.

A prospective clinical and biomechanical analysis of feet following first metatarsophalangeal joint arthrodesis for end stage hallux rigidus.

BACKGROUND: Hallux Rigidus is the result of degeneration of the 1st metatarsophalangeal joint (1st MTPJ). In end-stage hallux rigidus, treatment is mainly surgical with arthrodesis being a favourable option. Although the biomechanical effects of arthrodesis have been examined, a detailed comparison of pre- and post-operative biomechanics has yet to be conducted. RESEARCH QUESTION: Does 1st MTPJ arthrodesis positively affect foot kinematics and plantar pressure distribution? METHODS: Twelve 1st MTPJ arthrodesis were performed in patients with a mean age of 53.5 ± 5.4 years and follow up time of 6.9 ± 1.0 months. Pre- and post-operative data were collected at a CMAS (Clinical Movement Analysis Society) accredited gait laboratory using a BTS motion capture system and pedobarographic pressure plates. Patient outcome measures were also assessed using the MOXFQ. Statistical analysis was conducted using a two-way repeated measures ANOVA. RESULTS: Significant changes in stride length, cycle duration, cadence and velocity were identified following 1st MTPJ arthrodesis. A significant reduction in forefoot-hallux dorsiflexion at toe-off was identified for the operated foot from the pre-operative (20.23 ± 5.98°) to post-operative (7.56 ± 2.96°) assessment. Post-operative sagittal and transverse plane changes in the operated foot were also identified. Peak pressure and PTI results indicated significant lateralisation of load for the operated foot, but importantly this was not influenced following arthrodesis. Finally, there was a significant improvement in MOXFQ score. SIGNIFICANCE: Following 1st MTPJ fusion there is an improvement in overall gait mechanics which accompanied by the improved MOXFQ score indicates a reduction in pain and improved confidence during gait. The lack of post-operative dorsiflexion at forefoot-hallux caused load to remain lateralised and compensatory mechanisms to occur at the more proximal joints within the foot. These results provide valuable information for clinicians and will enable more accurate counselling to be provided to patients with end-stage hallux rigidus.

Evaluating the Role of AI in Predicting the Success of Dental Implants Based on Preoperative CBCT Images: A Randomized Controlled Trial.

Background: Dental implant surgery has become a widely accepted method for replacing missing teeth. However, the success of dental implant procedures can be influenced by various factors, including the quality of preoperative planning and assessment. Cone beam computed tomography (CBCT) imaging provides valuable insights into a patient's oral anatomy, but accurately predicting implant success remains a challenge. Materials and Methods: In this randomized controlled trial (RCT), a cohort of 150 patients requiring dental implants was randomly divided into two groups: an artificial intelligence (AI)-assisted group and a traditional assessment group. Preoperative CBCT images of all patients were acquired and processed. The AI-assisted group utilized a machine learning model trained on historical data to assess implant success probability based on CBCT images, while the traditional assessment group relied on conventional methods and clinician expertise. Key parameters such as bone density, bone quality, and anatomical features were considered in the AI model. Results: After the completion of the study, the AI-assisted group demonstrated a significantly higher implant success rate, with 92% of implants successfully integrating into the bone compared to 78% in the traditional assessment group. The AI model showed an accuracy of 87% in predicting implant success, whereas traditional assessment methods achieved an accuracy of 71%. Additionally, the AI-assisted group had a lower rate of complications and required fewer postoperative interventions compared to the traditional assessment group. Conclusion: The AI-assisted approach significantly improved implant success rates and reduced complications, underscoring the importance of incorporating AI into the dental implant planning process.

Molecular and Functional Characterization of Human Sex-Determining Region on the Y Chromosome Variants Using Protamine 1 Promoter.

The male sex-determining gene, sex-determining region on the Y chromosome (SRY), is expressed in adult testicular germ cells; however, its role in regulating spermatogenesis remains unclear. The role of SRY in the postmeiotic gene expression was investigated by determining the effect of SRY on the promoter of the haploid-specific Protamine 1 (PRM1) gene, which harbors five distinct SRY-binding motifs. In a luciferase reporter assay system, SRY upregulates PRM1 promoter activity in vitro in a dose-dependent manner. Through a gel-shift assay involving a 31-bp DNA fragment encompassing the SRY element within the PRM1 promoter, the third SRY-binding site on the sense strand (-373/-367) was identified as crucial for PRM1 promoter activation. This assay was extended to analyze 9 SRY variants found in the testicular DNA of 44 azoospermia patients. The findings suggest that SRY regulates PRM1 promoter activity by directly binding to its specific motif within the PRM1 promoter.

The antibodies against the computationally designed mimic of the glycoprotein hormone receptor transmembrane domain provide insights into receptor activation and suppress the constitutively activated receptor mutants.

The exoloops of glycoprotein hormone receptors (GpHRs) transduce the signal generated by the ligand-ectodomain interactions to the transmembrane helices either through direct hormonal contact and/or by modulating the interdomain interactions between the hinge region (HinR) and the transmembrane domain (TMD). The ligand-induced conformational alterations in the HinRs and the interhelical loops of luteinizing hormone receptor/follicle stimulating hormone receptor/thyroid stimulating hormone receptor were mapped using exoloop-specific antibodies generated against a mini-TMD protein designed to mimic the native exoloop conformations that were created by joining the thyroid stimulating hormone receptor exoloops constrained through helical tethers and library-derived linkers. The antibody against the mini-TMD specifically recognized all three GpHRs and inhibited the basal and hormone-stimulated cAMP production without affecting hormone binding. Interestingly, binding of the antibody to all three receptors was abolished by prior incubation of the receptors with the respective hormones, suggesting that the exoloops are buried in the hormone-receptor complexes. The antibody also suppressed the high basal activities of gain-of-function mutations in the HinRs, exoloops, and TMDs such as those involved in precocious puberty and thyroid toxic adenomas. Using the antibody and point/deletion/chimeric receptor mutants, we demonstrate that changes in the HinR-exoloop interactions play an important role in receptor activation. Computational analysis suggests that the mini-TMD antibodies act by conformationally locking the transmembrane helices by means of restraining the exoloops and the juxta-membrane regions. Using GpHRs as a model, we describe a novel computational approach of generating soluble TMD mimics that can be used to explain the role of exoloops during receptor activation and their interplay with TMDs.

Effective gene delivery using size dependant nano core-shell in human cervical cancer cell lines by magnetofection.

Biocompatible magnetic nanoparticles are effective for gene delivery in vitro and in vivo transfection. These mediators are mainly used to deliver drugs and genes. It can also be used as probes to diagnose and treat various diseases. Magnetic nanoparticles, primarily iron oxide nanoparticles, are used in various biological applications. However, preparing stable and small-size biocompatible core-shell is crucial in site direct gene delivery. In the present study, superparamagnetic iron oxide nanoparticles were synthesized using the chemical co-precipitation method and were functionalized with starch to attain stable particles. These SPIONs were coated with polyethylenimine to give a net positive charge. The fluorescent plasmid DNA bound to the SPIONs were used as a core shell for gene delivery into the HeLa cells via magnetofection. UV-Visible Spectrophotometry analysis showed a peak at 200 nm, which confirms the presence of FeO nanoparticles. The Scanning Electron Microscopy images revealed the formation of spherical-shaped nanoparticles with an average size of 10 nm. X-ray Diffraction also confirmed FeO as a significant constituent element. Vibrating Sample Magnetometry ensures that the nanoparticles are superparamagnetic. Atomic Force Microscopy images show the DNA bound on the surface of the nanoparticles. The gene delivery and transfection efficiency were analyzed by flow cytometry. These nanoparticles could effectively compact the pDNA, allowing efficient gene transfer into the HeLa cell lines.

Microkinetic insights into the role of catalyst and water activity on the nucleation, growth, and dissolution during COF-5 synthesis.

The chemical pathway for synthesizing covalent organic frameworks (COFs) involves a complex medley of reaction sequences over a rippling energy landscape that cannot be adequately described using existing theories. Even with the development of state-of-the-art experimental and computational tools, identifying primary mechanisms of nucleation and growth of COFs remains elusive. Other than empirically, little is known about how the catalyst composition and water activity affect the kinetics of the reaction pathway. Here, for the first time, we employ time-resolved in situ Fourier transform infrared spectroscopy (FT-IR) coupled with a six-parameter microkinetic model consisting of ∼10 million reactions and over 20 000 species. The integrated approach elucidates previously unrecognized roles of catalyst pKa on COF yield and water on growth rate and size distribution. COF crystalline yield increases with decreasing pKa of the catalysts, whereas the effect of water is to reduce the growth rate of COF and broaden the size distribution. The microkinetic model reproduces the experimental data and quantitatively predicts the role of synthesis conditions such as temperature, catalyst, and precursor concentration on the nucleation and growth rates. Furthermore, the model also validates the second-order reaction mechanism of COF-5 and predicts the activation barriers for classical and non-classical growth of COF-5 crystals. The microkinetic model developed here is generalizable to different COFs and other multicomponent systems.