Revolutionizing Leishmaniasis Treatment with Cutting Edge Drug Delivery Systems and Nanovaccines: An Updated Review.

Leishmaniasis, one of the most overlooked tropical diseases, is a life-threatening illness caused by the parasite Leishmania donovani that is prevalent in underdeveloped nations. Over 350 million individuals in more than 90 different nations worldwide are at risk of contracting the disease, which has a current fatality rate of 50 000 mortalities each year. The administration of liposomal Amp B, pentavalent antimonials, and miltefosine are still considered integral components of the chemotherapy regimen. Antileishmanial medications fail to treat leishmaniasis because of their numerous drawbacks. These include inadequate effectiveness, toxicity, undesired side effects, drug resistance, treatment duration, and cost. Consequently, there is a need to overcome the limitations of conventional therapeutics. Nanotechnology has demonstrated promising outcomes in addressing these issues because of its small size and distinctive characteristics, such as enhanced bioavailability, lower toxicity, biodegradability, and targeted drug delivery. This review is an effort to highlight the recent progress in various nanodrug delivery systems (nDDSs) over the past five years for treating leishmaniasis. Although the preclinical outcomes of nDDSs have shown promising treatment for leishmaniasis, further research is needed for their clinical translation. Advancement in three primary priority domains─molecular diagnostics, clinical investigation, and knowledge dissemination and standardization─is imperative to propel the leishmaniasis field toward translational outcomes.

Spatio-temporal expression of polyphenol oxidase unveils the dynamics of L-DOPA accumulation in faba bean (Vicia faba L.).

Faba bean (Vicia faba L.) is a winter season grain legume and a rich source of the anti-parkinson drug, L-3,4-dihydroxyphenylalanine (L-DOPA). The biosynthesis of L-DOPA in plants is not uniform and remains largely unexplored. While the hydroxylase activities of Tyrosine Hydroxylase (TH), the Cytochrome P450 (CYP450) class of enzymes, and Polyphenol Oxidases (PPOs) on tyrosine substrate have been reported in plants, only the roles of PPOs in L-DOPA biosynthesis have been recently established in velvet bean (Mucuna pruriens). To understand the differential accumulation of L-DOPA in different tissues of faba bean, profiling of L-Tyrosine, L-DOPA, Tyramine, and Dopamine in different tissues was performed. Differential accumulation of L-DOPA depended on tissue type and maturity. Furthermore, dopamine biosynthesis through L-DOPA from L-Tyr was confirmed in faba bean. The expression analysis of PPOs in leaf and flower tissues revealed the selective induction of only four (HePPO-2, HePPO-7, HePPO-8b, and HePPO-10) out of ten genes encoding different PPOs mined from the faba bean genome. Higher accumulation of L-DOPA in young leaves and flower buds than in mature leaves and flowers was accompanied by significantly higher expression of HePPO-10 and HePPO-7, respectively. The role of various transcription factors contributing to such metabolite dynamics was also predicted. Further exploration of this mechanism using a multi-omics approach can provide meaningful insight and pave the way for enhancing L-DOPA content in crops. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01449-2.

Neurogenic and angiogenic poly(N-acryloylglycine)-co-(acrylamide)-co-(N-acryloyl-glutamate) hydrogel: preconditioning effect under oxidative stress and use in neuroregeneration.

Traumatic injuries, neurodegenerative diseases and oxidative stress serve as the early biomarkers for neuronal damage and impede angiogenesis and subsequently neuronal growth. Considering this, the present work aimed to develop a poly(N-acryloylglycine)-co-(acrylamide)-co-(N-acryloylglutamate) hydrogel [p(NAG-Ac-NAE)] with angiogenesis/neurogenesis properties. As constituents of this polymer modulate their vital role in biological functions, inhibitory neurotransmitter glycine regulates neuronal homeostasis, and glutamatergic signalling regulates angiogenesis. The p(NAG-Ac-NAE) hydrogel is a highly branched, biodegradable and pH-responsive polymer with a very high swelling behavior of 6188%. The mechanical stability (G', 2.3-2.7 kPa) of this polymeric hydrogel is commendable in the differentiation of mature neurons. This hydrogel is biocompatible (as tested in HUVEC cells) and helps to proliferate PC12 cells (152.7 ± 13.7%), whereas it is cytotoxic towards aggressive cancers such as glioblastoma (LN229 cells) and triple negative breast cancer (TNBC; MDA-MB-231 cells) and helps to maintain the healthy cytoskeleton framework structure of primary cortical neurons by facilitating the elongation of the axonal pathway. Furthermore, FACS results revealed that the synthesized hydrogel potentiates neurogenesis by inducing the cell cycle (G0/G1) and arresting the sub-G1 phase by limiting apoptosis. Additionally, RT-PCR results revealed that this hydrogel induced an increased level of HIF-1α expression, providing preconditioning effects towards neuronal cells under oxidative stress by scavenging ROS and initiating neurogenic and angiogenic signalling. This hydrogel further exhibits more pro-angiogenic activities by increasing the expression of VEGF isoforms compared to previously reported hydrogels. In conclusion, the newly synthesized p(NAG-Ac-NAE) hydrogel can be one of the potential neuroregenerative materials for vasculogenesis-assisted neurogenic applications and paramount for the management of neurodegenerative diseases.

Development of a FRET aptasensor based on MoS2-doped Zn-MOF as luminophore for selective detection of cadmium in aqueous solutions.

A robust "on-off" fluorescent aptasensor was developed using nanohybrids of molybdenum sulfide (MoS2) quantum dot (QD)-doped zinc metal-organic frameworks (Zn-MOF) for selective and sensitive detection of cadmium ions (Cd2+) in water. This nanohybrid (MoS2@Zn-MOF), synthesized via "bottle around the ship" methodology, exhibited a high-intensity fluorescence emission centered at 430 nm (λEm) (blue) on excitation at 320 nm (λEx). Further, the conjugation of this fluorophore to phosphate-modified cadmium aptamer (Cd-2-2) was achieved through carbodiimide reaction. The hybridization of prepared sensing probe (MoS2@Zn-MOF/Cd-2-2 aptamer) was done with dabcyl-conjugated complementary DNA (cDNA), acting as energy donor-acceptor pair in the fluorescence resonance energy transfer (FRET) system. This hybridization causes the fluorescence quenching of the nanohybrid. In the presence of Cd2+, the aptamer from the fabricated nano-biosensing probe binds to these ions, resulting in release of dabcyl-cDNA oligomer. This release of dabcyl-cDNA oligomer from the sensing probes restores the fluorescence of the nanohybrid. Under optimized conditions (sensing probe/dabcyl-cDNA ratio 1/7, pH 7.4, and temp 28 °C), the sensing probe showed a fast response time of 1 min. The fluorescence intensity of the nanohybrid can be utilized to determine the concentration of Cd2+. The proposed aptasensor achieved highly sensitive detection of Cd2+ with a limit of detection (LOD) of 0.24 ppb over the range of 1 × 10-9 to 1 × 10-4 M along with minimal effects of interferences (e.g., Hg2+, Pb2+, and Zn2+) and good reproducibility. The designed aptasensor based on MoS2@Zn-MOF nanofluorophore offers a highly sensitive and selective approach for rapid screening of metal ions in aqueous environments.

Evaluation of the non-endoscopic and endoscopic-assisted platysma flap - A randomized control trial.

Background and Aim: As oral submucous fibrosis (OSMF) is a chronic progressive disorder, the treatment is based on the severity of the disease. Surgical treatment is the only choice for grade III and grade IV OSMF cases because the patient can neither clean his/her mouth nor properly chew. The resulting soft tissue defect requires resurfacing with various well-vascularized tissues such as extraoral flaps, intraoral flaps, microvascular flaps, and allografts that have been used. Reconstruction of the resultant defects proved to be challenging. Till date, none of the flaps has been proven to be effective and is universally accepted for the treatment of OSMF because of various drawbacks of the available techniques. This study was conducted to know whether an endoscopic-assisted platysma flap is associated with better outcomes in terms of ease of operation and postoperative function than the conventional approach. Materials and Methods: This study included 40 patients of grade III and grade IV OSMF reporting to the outpatient department of oral and maxillofacial surgery in a tertiary center of North India. These patients were divided randomly into two groups. Group I and Group II had 20 patients each, undergoing endoscopic-assisted platysma flap and non-endoscopic-assisted platysma flap for reconstruction after resection of OSMF bands, respectively. Data were analyzed for the mouth opening, operating time, flap viability, congestion of neck and oral cavity, signs of inflammation, neurologic assessment, and measurement of the drain. Results: The results showed significant increase in mouth opening from the preoperative value to the values immediately after surgery and at 24 h, 1 week, 15 days, 1 month, 3 months, and 6 months after surgery in both the study groups. Reduced bleeding incidence was found in group I compared to group II, with better postoperative outcomes noted during follow-up. But the mean intraoperative time of the subjects in group I was 130.80 ± 5.5.908 min and in group II was 105.74 ± 2. 491 min. Increased time taken in group I may be due to the long learning curve. Conclusion: The present study concluded that the Endoscope-assisted technique has a key role during supra and subplatysmal dissection to allow for better accessibility, handling, and visibility of the flap and its orientation in relation to the underlying structures to avoid postoperative complications and to overcome the drawback of platysma myocutaneous flap in reconstruction of OSMF defects.

Synthesized Gold Nanoparticles with Moringa Oleifera leaf Extract Induce Mitotic Arrest (G2/M phase) and Apoptosis in Dalton's Lymphoma Cells.

The therapeutic potential of chemically synthesized AuNPs has been demonstrated in various types of cancer. However, gold nanoparticles (AuNPs) synthesized using typical chemical methods have concerns regarding their environmental safety and adverse impact on human well-being. To overcome this issue, we used an environmentally friendly approach in which gold nanoparticles were synthesized using Moringa oleifera leaf extract (MLE). The present research was mainly focused on the biosynthesis and characterization of gold nanoparticles (AuNPs) using Moringa oleifera leaf extract (MLE-AuNPs) and explore its anticancer potential against Dalton's Lymphoma (DL) cells. Characterization of the MLE-AuNPs was conducted using UV-Vis Spectroscopy to confirm the reduction process, FTIR analysis to ascertain the presence of functional groups, and XRD analysis to confirm the crystallinity. SEM and TEM images were used to examine size and morphology. After characterization, MLE-AuNPs were evaluated for their cytotoxic effects on Dalton's lymphoma cells, and the results showed an IC50 value of 75 ± 2.31 µg/mL; however, there was no discernible cytotoxicity towards normal murine thymocytes. Furthermore, flow cytometric analysis revealed G2/M phase cell cycle arrest mediated by the downregulation of cyclin B1 and Cdc2 and upregulation of p21. Additionally, apoptosis induction was evidenced by Annexin V Staining, accompanied by modulation of apoptosis-related genes including decreased Bcl-2 expression and increased expression of Bax, Cyt-c, and Caspase-3 at both the mRNA and protein levels. Collectively, our findings underscore the promising anti-cancer properties of MLE-AuNPs, advocating their potential as a novel therapeutic avenue for Dalton's lymphoma.

Development and Validation of Fast and Sensitive RP-HPLC Stability-Indicating Method for Quantification of Piroxicam in Bulk Drug.

A simple, rapid, sensitive, and cost-effective green solvent-assisted reverse-phase high-performance liquid chromatographic technique, coupled with a photodiode array detector, was developed and validated for the estimation of piroxicam (PRXM). The chromatographic separation was achieved by using a C-18 (250 × 4.6) mm, 5-µm stationary phase and a mobile phase consisting of methanol and 0.1% ortho-phosphoric acid in water in a ratio of (80:20) v/v at a flow rate of 1 ml/min. The detection was carried out at a wavelength of 254 nm with a constant injection volume of 10 µL throughout the analysis. The calibration curve was observed to be linear over the optimum concentration range of 50-300 µg mL-1, with an R2 value of 0.9995. The developed method was validated as per the International Council for Harmonisation (ICH) Q2 (R1) guideline. Various parameters like selectivity/specificity, accuracy/recovery, linearity, precision, detection limit, quantitation limit, robustness and stability of analyte in solution were performed for the method validation. The PRXM was evaluated under stressed conditions, including acidic, basic, oxidative, thermal and photolytic, as per ICH Q1 (R2) guidelines. Significant degradation was observed in acidic and basic degradation conditions. Conversely, the drug substance showed stability when exposed to oxidative, photolytic and thermal degradation conditions.

Enhancing cancer immunotherapy: Exploring strategies to target the PD-1/PD-L1 axis and analyzing the associated patent, regulatory, and clinical trial landscape.

Cancer treatment modalities and their progression is guided by the specifics of cancer, including its type and site of localization. Surgery, radiation, and chemotherapy are the most often used conventional treatments. Conversely, emerging treatment techniques include immunotherapy, hormone therapy, anti-angiogenic therapy, dendritic cell-based immunotherapy, and stem cell therapy. Immune checkpoint inhibitors' anticancer properties have drawn considerable attention in recent studies in the cancer research domain. Programmed Cell Death Protein-1 (PD-1) and its ligand (PD-L1) checkpoint pathway are key regulators of the interactions between activated T-cells and cancer cells, protecting the latter from immune destruction. When the ligand PD-L1 attaches to the receptor PD-1, T-cells are prevented from destroying cells that contain PD-L1, including cancer cells. The PD-1/PD-L1 checkpoint inhibitors block them, boosting the immune response and strengthening the body's defenses against tumors. Recent years have seen incredible progress and tremendous advancement in developing anticancer therapies using PD-1/PD-L1 targeting antibodies. While immune-related adverse effects and low response rates significantly limit these therapies, there is a need for research on methods that raise their efficacy and lower their toxicity. This review discusses various recent innovative nanomedicine strategies such as PLGA nanoparticles, carbon nanotubes and drug loaded liposomes to treat cancer targeting PD-1/PD-L1 axis. The biological implications of PD-1/PD-L1 in cancer treatment and the fundamentals of nanotechnology, focusing on the novel strategies used in nanomedicine, are widely discussed along with the corresponding guidelines, clinical trial status, and the patent landscape of such formulations.

TWISP: A Transgenic Worm for Interrogating Signal Propagation in C. elegans.

Genetically encoded optical indicators and actuators of neural activity allow for all-optical investigations of signaling in the nervous system. But commonly used indicators, actuators and expression strategies are poorly suited for systematic measurements of signal propagation at brain scale and cellular resolution. Large scale measurements of the brain require indicators and actuators with compatible excitation spectra to avoid optical crosstalk. They must be highly expressed in every neuron but at the same time avoid lethality and permit the animal to reach adulthood. Their expression must also be compatible with additional fluorescent labels to locate and identify neurons, such as those in the NeuroPAL cell identification system. We present TWISP, a Transgenic Worm for Interrogating Signal Propagation, that addresses these needs and enables optical measurements of evoked calcium activity at brain scale and cellular resolution in the nervous system of the nematode Caenorhabditis elegans. We express in every neuron a non-conventional optical actuator, the gustatory receptor homolog GUR-3 + PRDX-2 under the control of a drug-inducible system QF + hGR, and calcium indicator GCAMP6 s, in a background with additional fluorophores of the NeuroPAL cell ID system. We show that this combination, but not others tested, avoids optical-crosstalk, creates strong expression in the adult, and generates stable transgenic lines for systematic measurements of signal propagation in the worm brain.

Biomass-derived carbon dots as significant biological tools in the medicinal field: A review.

Early disease detection is crucial since it raises the likelihood of treatment and considerably lowers the cost of therapy. Therefore, the improvement of human life and health depends on the development of quick, efficient, and credible biosensing methods. For improving the quality of biosensors, distinct nanostructures have been investigated; among these, carbon dots have gained much interest because of their great performance. Carbon dots, the essential component of fluorescence nanoparticles, having outstanding chemical characteristics, superb biocompatibility, chemical inertness, low toxicity and potential optical characteristics have attracted the researchers from every corner of the globe. Several carbon dots applications have been thoroughly investigated in recent decade, from optoelectronics to biomedical investigations. This review study primarily emphasizes the recent advancements in the field of biomass-derived carbon dots-based drug delivery, gene delivery and bioimaging, and highlights achievements in two major areas: in vivo applications that involve carbon dots absorption in zebrafish and mice, tumour therapeutics, and imaging-guided drug delivery. Additionally, the possible advantages, difficulties, and future possibilities of using carbon dots for biological applications are also explored.

Synthesis, characterization and photophysical studies of dual-emissive base-modified fluorescent nucleosides.

A straightforward and efficient methodology has been employed for the synthesis of a diverse set of base-modified fluorescent nucleoside conjugates via Cu(I)-catalysed cycloaddition reaction of 5-ethynyl-2',3',5'-tri-O-acetyluridine/3',5'-di-O-acetyl-2'-deoxyuridine with 4-(azidomethyl)-N9-(4'-aryl)-9,10-dihydro-2H,8H-chromeno[8,7-e][1,3]oxazin-2-ones in tBuOH to afford the desired 1,2,3-triazoles in 92-95% yields. Treatment with NaOMe/MeOH resulted in the final deprotected nucleoside analogues. The synthesized 1,2,3-triazoles demonstrated a significant emission spectrum, featuring two robust bands in the region from 350-500 nm (with excitation at 300 nm) in fluorescence studies. Photophysical investigations revealed a dual-emissive band with high fluorescence intensity, excellent Stokes shift (140-164 nm) and superior quantum yields (0.068-0.350). Furthermore, the electronic structures of the synthesized triazoles have been further verified by DFT studies. Structural characterization of all synthesized compounds was carried out using various analytical techniques, including IR, 1H-NMR, 13C-NMR, 1H-1H COSY, 1H-13C HETCOR experiments, and HRMS measurements. The dual-emissive nature of these nucleosides would be a significant contribution to nucleoside chemistry as there are limited literature reports on the same.

Functional Outcomes and Their Influencing Factors for the Surgical Management of T-type Acetabulum Fractures: A Prospective Single-Centre Study of 73 Patients.

Introduction T-type fractures of the acetabulum are uncommon injuries, typically resulting in poorer long-term outcomes compared to other patterns of acetabular fractures. Our main purpose is to analyse the epidemiology, functional outcomes, and factors affecting the functional outcomes of patients with T-type acetabular fractures. Methods This prospective, single-centre study included 73 patients with T-type and T with posterior wall acetabular fractures. They underwent treatment with open reduction internal fixation using plating through the modified Stoppa, Kocher-Langenbeck (KL), or dual approach. The post-operative reduction was assessed according to Matta's criteria, and functional outcomes were evaluated using the modified Harris hip score. Results Between September 2017 and January 2023, 53 patients underwent surgery for T-type fractures (72.6%), and 20 patients were treated for T with posterior wall acetabular fractures (27.4%). The minimum follow-up period was one year, with a mean follow-up of 3.5 years. Anatomical reduction emerged as the major contributing factor towards good functional outcomes compared to satisfactory reduction according to Matta's criteria (P value: 0.006). Overall, 65 patients (89%) achieved excellent to good modified Harris hip scores, while eight patients (11%) obtained fair to poor scores. Patients with T-type fractures demonstrated better functional outcomes compared to T with posterior wall fractures (P value: 0.031). Conclusion Anatomical reduction, as assessed by Matta's reduction criteria, serves as a predictor of favourable functional outcomes. T with posterior wall fractures exhibit poor outcomes in comparison to T-type fractures. The surgical approach employed does not influence the reduction or the final functional outcome of the patient.

Lipid composition differs in diapause and nondiapause states of spotted stem borer, Chilo partellus.

Spotted stem borer, Chilo partellus, undergoes larval diapause (hibernation and aestivation), and depends on the food reserve accumulated during feeding stage for its survival. Lipids are the primary source of energy during diapause, and essential for different cellular, biochemical and physiological functions. However, there is no information on lipid and lipophilic compound contents during different stages of hibernation, aestivation and nondiapause in C. partellus. Thus, we compared the concentration and composition of lipids in pre-diapause, diapause and post-diapause stages of hibernation and aestivation with nondiapause stages of C. partellus. The studies revealed significant differences in total lipids and various lipophilic compounds during different stages of diapause as compared to nondiapause C. partellus. The total lipids were significantly lower during diapause stage of aestivation and hibernation as compared to nondiapause larvae. Further, the linoleic acid, Methyl 3-methoxytetradecanoate, and l-(+)-Ascorbic acid 2,6-dihexadecanoate were significantly lower, and oleic and palmitoleic acids greater during pre-diapause and diapause stages of hibernation and aestivation as compared to nondiapause larvae. The cholesterol content was significantly greater during pre-diapause stage of hibernation, and diapause and post-diapause stages of aestivation as compared to nondiapause stages. The unsaturation ratio was significantly higher in the pre-diapause and diapause stages and lower in post-diapause stage of aestivation than the hibernation and nondiapause states. This study provides insights on differential lipid profiles during different phases of diapause, which could be useful for further understanding biochemical and physiological cross-talk, and develop target-specific technologies for the management of C. partellus.

Best practices for machine learning in antibody discovery and development.

In the past 40 years, therapeutic antibody discovery and development have advanced considerably, with machine learning (ML) offering a promising way to speed up the process by reducing costs and the number of experiments required. Recent progress in ML-guided antibody design and development (D&D) has been hindered by the diversity of data sets and evaluation methods, which makes it difficult to conduct comparisons and assess utility. Establishing standards and guidelines will be crucial for the wider adoption of ML and the advancement of the field. This perspective critically reviews current practices, highlights common pitfalls and proposes method development and evaluation guidelines for various ML-based techniques in therapeutic antibody D&D. Addressing challenges across the ML process, best practices are recommended for each stage to enhance reproducibility and progress.

De-risking Pretreatment of Microalgae To Produce Fuels and Chemical Co-products.

Conversion of microalgae to renewable fuels and chemical co-products by pretreating and fractionation holds promise as an algal biorefinery concept, but a better understanding of the pretreatment performance as a function of algae strain and composition is necessary to de-risk algae conversion operations. Similarly, there are few examples of algae pretreatment at scales larger than the bench scale. This work aims to de-risk algal biorefinery operations by evaluating the pretreatment performance across nine different microalgae samples and five different pretreatment methods at small (5 mL) scale and further de-risk the operation by scaling pretreatment for one species to the 80 L scale. The pretreatment performance was evaluated by solubilization of feedstock carbon and nitrogen [as total organic carbon (TOC) and total nitrogen (TN)] into the aqueous hydrolysate and extractability of lipids [as fatty acid methyl esters (FAMEs)] from the pretreated solids. A range of responses was noted among the algae samples across pretreatments, with the current dilute Brønsted acid pretreatment using H2SO4 being the most consistent and robust. This pretreatment produced TOC yields to the hydrolysate ranging from 27.7 to 51.1%, TN yields ranging from 12.3 to 76.2%, and FAME yields ranging from 57.9 to 89.9%. In contrast, the other explored pretreatments (other dilute acid pretreatments, dilute alkali pretreatment with NaOH, enzymatic pretreatment, and flash hydrolysis) produced lower or more variable yields across the three metrics. In light of the greater consistency across samples for dilute acid pretreatment, this method was scaled to 80 L to demonstrate scalability with microalgae feedstocks.

Efficacy and safety of burosumab compared with conventional therapy in patients with X-linked hypophosphatemia: A systematic review.

Burosumab, a monoclonal antibody directed against the fibroblast growth factor 23 (FGF23), has been approved for the treatment of X-linked hypophosphatemia (XLH). We conducted a systematic review to compare the efficacy and safety of burosumab versus conventional therapy (phosphorus and calcitriol) on XLH treatment. After a comprehensive literature search on MEDLINE/PubMed and Embase, we found nine studies for inclusion in the analysis. Risk of bias was assessed, and a random-effects model was used to determine the effect size. Clinical, biochemical, and radiological parameters of disease severity before and after treatment were analyzed and expressed in standardized mean difference (SMD). Burosumab resulted in normalization of phosphate homeostasis with an increase in renal tubular phosphate reabsorption and significant resolution of skeletal lesions (change in Thacher's total rickets severity score SMD: -1.46, 95% confidence interval [CI]: -1.76 to -1.17, p < 0.001, improvement in deformities, and decline in serum alkaline phosphatase levels [SMD: 130.68, 95% CI: 125.26-136.1, p < 0.001)]. Conventional therapy led to similar improvements in all these parameters but to a lower degree. In adults, burosumab normalized phosphorus levels (SMD: 1.23, 95% CI: 0.98-1.47, p < 0.001) with resultant clinical improvement. Burosumab treatment was well tolerated, with only mild treatment-related adverse effects. The present review indicates a potential role for burosumab in improving rickets, deformities, and growth in children with XLH. Given its superior efficacy and safety profile, burosumab could be an effective therapeutic option in children. We suggest further studies comparing burosumab versus conventional therapy in children and adults with XLH.

Role of Cholesterol in Interaction of Ionic Liquids with Model Lipid Membranes and Associated Permeability.

In this work, we explored how the amount of cholesterol in the lipid membrane composed of phosphatidylcholine (POPC) or phosphatidylglycerol (POPG) affects the interaction with 1-dodecyl-3-methylimidazolium bromide ([C12MIM]+Br-) ionic liquids using various biophysical techniques. On interacting with the membrane, [C12MIM]+Br- leads to enhanced membrane permeability and induces membrane fusion, leading to an increase in vesicle size. The 2H-based solid-state NMR investigations of cholesterol-containing lipid membranes reveal that [C12MIM]+Br- decreases the lipid chain order parameters and counteracts the lipid condensation effect of cholesterol to some extent. Therefore, as the amount of cholesterol in the membrane increases, the membrane effect of [C12MIM]+Br- decreases. The effect of [C12MIM]+Br- on the membrane properties is more pronounced for POPC compared to that of POPG membranes. This suggests a dependence of these effects on the electrostatic interactions, indicating that the influence of [C12MIM]+Br- varies based on the lipid composition. The findings suggest that the presence of cholesterol can modulate the effect of [C12MIM]+Br- on membrane properties, with variations observed between POPC and POPG membranes, highlighting the importance of lipid composition. In short, this study provides insights into the intricate interplay between cholesterol, the lipid membrane, and the ionic liquid [C12MIM]+Br-.

Visible Light-Promoted Regioselective Benzannulation of Vinyl Sulfoxonium Ylides with Ynoates.

Herein, we report a highly regioselective [4 + 2]-annulation of vinyl sulfoxonium ylides with ynoates under light-mediated conditions. The reaction proceeds through the new dienyl sulfoxonium ylide, which undergoes photolysis under blue light irradiation to give highly substituted naphthalene scaffolds. The method presented here operates at room temperature and does not require the addition of an external photosensitizer. The in situ-generated dienyl sulfoxonium ylide absorbs light and acts as a photosensitizer for the formation of arenes. The synthetic potential of these benzannulations was further illustrated by various synthetic transformations and a scale-up reaction. Moreover, control experiments and quantum chemical calculations reveal the mechanistic details of the developed reaction.

Evaluation of Bond Strength and Adhesive Remnant Index of Different Lingual Retainers in Human Incisor Teeth.

Objective: This study aimed to evaluate and compare the bond strengths of four different lingual retainers and assess the adhesive remnant index (ARI) to determine their effectiveness in orthodontic retention. Methodology: Eighty human incisor teeth were divided into four groups, with each group bonded using a different retainer: Group 1 (E-Glass retainer), Group 2 (0.017" Co-axial stainless steel wire), Group 3 (Splint C.T. fiber mesh), and Group 4 (0.010" stainless steel ligature wire). Bond strength was measured using a universal testing machine, and ARI scores were recorded to assess bond failure types. Results: Group 1 (E-Glass retainer) demonstrated the highest bond strength, followed by Group 3 (Splint C.T. fiber mesh), Group 2 (Co-axial stainless steel wire), and Group 4 (stainless steel ligature wire). Cohesive bond failures were observed in most groups, except for the co-axial stainless steel wire group, which exhibited adhesive failures. Conclusion: E-Glass fiber-reinforced retainers showed the highest bond strength, making them a promising alternative to conventional stainless steel wires for orthodontic retention, especially in patients with esthetic concerns or nickel hypersensitivity. Stainless steel retainer groups exhibited lower bond strengths, and cohesive bond failures were prevalent. Further research is needed to validate these findings in clinical settings and evaluate the long-term effectiveness of different lingual retainers.