Aqueous Graphene Dispersion and Biofunctionalization via Enzymatic Oxidation of Tripeptides.

Graphene, a 2D carbon material, possesses extraordinary mechanical, electrical, and thermal properties, making it highly attractive for various biological applications such as biosensing, biotherapeutics, and tissue engineering. However, the tendency of graphene sheets to aggregate and restack hinders its dispersion in water, limiting these applications. Peptides, with their defined amino acid sequences and versatile functionalities, are compelling molecules with which to modify graphene-aromatic amino acids can strengthen interactions through π-stacking and charged groups can be chosen to make the sheets dispersible and stable in water. Here, a facile and green method for covalently functionalizing and dispersing graphene using amphiphilic tripeptides, facilitated by a tyrosine phenol side chain, through an aqueous enzymatic oxidation process is demonstrated. The presence of a second aromatic side chain group enhances this interaction through non-covalent support via π-π stacking with the graphene surface. Futhermore, the addition of charged moieties originating from either ionizable amino acids or terminal groups facilitates profound interactions with water, resulting in the dispersion of the newly functionalized graphene in aqueous solutions. This biofunctionalization method resulted in ≈56% peptide loading on the graphene surface, leading to graphene dispersions that remain stable for months in aqueous solutions outperforming currently used surfactants.

Assessment of neurovascular channels in lateral maxillary sinus wall using cone-beam computed tomography: An imperative clinicians guide for implant placements.

Background: The aim of this study is to evaluate the location and radio morphometric features of the posterior superior alveolar artery (PSAA) in patients undergoing rehabilitation of posterior maxilla and other sinus augmentation surgical procedures by cone-beam computed tomography (CBCT). Materials and Methods: A total of 816 CBCT scans were included. Various radio morphometric measurements were done to assess the PSAA location, diameter, and distances to the sinus floor and alveolar crest. Results: The PSAA was mostly intraosseous in the maximum in the age group 31-51 years (56%), in males (53.4%), and in dentate patients (57.4%). The artery tends to be wider in older patients. Distances to the sinus floor or the alveolar crest tend to be shorter in women. Conclusions: This study suggests that CBCT is a valuable pre-surgical tool and the evaluation of the PSAA on CBCT images could reduce the likelihood of excess bleeding during surgery in the maxillary posterior region.

Surgical Scissors: The Core Surgical Instrument.

Surgical scissors form an essential part of both basic and specialty surgical sets. Their prime function is to cut tissues. They are also used for blunt dissection/development of tissue planes and piercing tissues. A wide variety of scissors are available for use in practice. This review article briefly describes common surgical scissors in orthopaedic use. The basic construct, biomechanics, types, their identification, specific uses, and care aspects are also discussed. A surgeon should be aware of the different types of scissors, their biomechanical features, and specific uses, as they are an important tool in his/her armamentarium. (Journal of Surgical Orthopaedic Advances 33(1):001-004, 2024).

Transforming Medicinal Oil into Advanced Gel: An Update on Advancements.

The present study delves into the evolution of traditional Ayurvedic oil preparations through innovative strategies to develop advanced gel formulations, aiming at amplifying their therapeutic efficacy. Ayurvedic oils have a rich historical context in healing practices, yet their conversion into contemporary gel-based formulations represents a revolutionary approach to augment their medicinal potential. The primary objective of this transformation is to leverage scientific advancements and modern pharmaceutical techniques to enhance the application, absorption, and overall therapeutic impact of these traditional remedies. By encapsulating the essential constituents of Ayurvedic oils within gel matrices, these novel strategies endeavor to improve their stability, bioavailability, and targeted delivery mechanisms. This review highlights the fusion of traditional Ayurvedic wisdom with cutting-edge pharmaceutical technology, paving the way for more effective and accessible utilization of these revered remedies in modern healthcare.

Effectiveness of Semecarpus anacardium Linn. fruits in cancer and inflammatory diseases: A mini review.

BACKGROUND: Semecarpus anacardium Linn. (SCA) fruits are found in India's sub-Himalayan, tropical, and central regions and have been utilized for centuries in traditional Indian medicine to treat various ailments. In recent times, a growing body of research has emerged indicating that the extracts and active components found in SCA fruits possess qualities that can potentially inhibit the development of cancer and inflammatory markers. PURPOSE: This study aims to provide a comprehensive review of the existing literature on the pharmacological mechanisms underlying the effects of extracts and phytochemicals of SCA fruits in cellular, animal models, and clinical trials of cancer and inflammatory diseases. METHODS: A comprehensive literature search was conducted utilizing several databases, including PubMed, Scopus, Google Scholar, preprint platforms, and the Cochrane Database of Systematic Reviews using the keywords "Semecarpus anacardium", "Anti-inflammatory," and "cancer". The collection of articles started with establishing the database and continued until April 2024. RESULTS: Out of 1130 retrieved database records, 316 pertained to systematic reviews. The remaining 814 records focused on examining the anticancer and anti-inflammatory properties of SCA fruits. In the course of these investigations, the four primary cancer types linked to SCA fruits are identified as lung cancer, hepatocellular carcinoma, breast cancer, and blood cancer. CONCLUSION: The findings will provide more support for investigating SCA fruits in cancer treatment and will furnish thorough reference data and recommendations for future studies on this botanical medication.

Droplet-based microfluidics and enzyme evolution.

Enzymes are widely used as catalysts in the chemical and pharmaceutical industries. While successful in many situations, they must usually be adapted to operate efficiently under nonnatural conditions. Enzyme engineering allows the creation of novel enzymes that are stable at elevated temperatures or have higher activities and selectivities. Current enzyme engineering techniques require the production and testing of enzyme variant libraries to identify members with desired attributes. Unfortunately, traditional screening methods cannot screen such large mutagenesis libraries in a robust and timely manner. Droplet-based microfluidic systems can produce, process, and sort picoliter droplets at kilohertz rates and have emerged as powerful tools for library screening and thus enzyme engineering. We describe how droplet-based microfluidics has been used to advance directed evolution.

Mass spectrometry-based proteomic analysis to characterize cisplatin induced early signaling events in head and neck squamous cell carcinoma.

Cisplatin is the commonly used chemotherapeutic drug in treatment of various cancers. However, development of resistance towards cisplatin results in tumor recurrence. Here, we aim to understand the mechanisms of action of cisplatin and emergence of resistance to cisplatin using mass spectrometry-based proteomic approach. A panel of head and neck squamous cell carcinoma (HNSCC) cell lines were treated with cisplatin at respective IC50 for 24 h and label-free mass spectrometry analysis was carried out. Proteomic analysis of A253, FaDu, Det562 and CAL27 cell lines upon cisplatin treatment resulted in the identification of 5,060, 4,816, 4,537 and 4,142 proteins, respectively. Bioinformatics analysis of differentially regulated proteins revealed proteins implicated in DNA damage bypass pathway, translation and mRNA splicing to be enriched. Further, proteins associated with cisplatin resistance exhibited alterations following short-term cisplatin exposure. Among these, class III tubullin protein (TUBB3) was found to be upregulated in cisplatin-treated cells compared to untreated cells. Western blot analysis confirmed the elevated expression of TUBB3 in cells treated with cisplatin for 24 h, and also in cisplatin resistant HNSCC cell lines. This study delineates the early signaling events that enable HNSCC cells to counteract the cytotoxic effects of cisplatin and facilitate the development of resistance.

Factors influencing correction rate following hemiepiphysiodesis using tension band plates for deformities around the knee: a multivariate analysis study.

PURPOSE: The aim of this study was to appraise various factors influencing the correction rate in temporary hemiepiphysiodesis (THE) around the knee joint. Specifically, the study analysed the relationship of correction rate with age, gender, aetiology, type and location of deformity. METHODS: The retrospective study included children who underwent THE for a coronal plane deformity (genu valgus or varum) around the knee joint (distal femur or proximal tibia) over a ten year period (2010-2020). The primary outcome of interest was the correction rate of the deformity. RESULTS: Thirty-three children (27 females and 6 males) with a mean age of 8.1 years involving 86 plates were included in the study. The mean correction achieved was 12.2° over a treatment period of 13.3 months. Subgroup analysis showed significant differences between the type (varus (0.8° per month), valgus (1.1° per month)) and the location of deformity femur (1.2° per month) and tibia (0.7° per month)]. On multivariate analysis, the location and the duration of treatment showed significant associations with the correction rate. CONCLUSION: The correction of coronal deformities following temporary hemiepiphysiodesis is influenced by several factors. Valgus, femoral and deformities in younger children correct at a faster rate. Location of deformity and duration of treatment emerged as potential factors affecting the correction rate.

Impact of Vacancy Defects on Electrochemical Nitrogen Reduction Reaction Performance of MXenes.

We investigated electrochemical nitrogen reduction reaction (eNRR) on MXenes consisting of the vacancy defects in the functional layer using density functional theory calculations. We considered Mo2C, W2C, Mo2N, and W2N MXenes with F, N, and O functionalization and investigated distal and alternative associative pathways. We analyzed these MXenes for eNRR based on N2 adsorption energy, NH3 desorption energy, NRR selectivity, and electrochemical limiting potential. While we find that most of the considered MXenes surfaces are more favorable for eNRR compared to hydrogen evolution, these surfaces also have strong NH3 binding (>-1.0 eV) and thus will be covered with NH3 during operating conditions. Amongst all considered MXenes, only W2NF2 is found to have a low NH3 desorption energy along with low eNRR overpotential and selectivity towards eNRR. The obtained eNRR overpotential and NH3 desorption energy on W2NF2 are superior to those reported for pristine W2N3 as well as functionalized MXenes.

Usefulness of skills in point of care ultrasound and simulation-based training as essential competencies in acute management of neonatal cardiac tamponade.

Peripherally inserted central catheter (PICC) insertion is a routine procedure in the neonatal intensive care unit required for prolonged intravenous fluid, nutrition and medication support. Neonatal cardiac tamponade is a serious and rare complication of PICC line insertion. Early detection by point of care ultrasound (POCUS) and management by pericardiocentesis improves the chances of survival. Regular simulation-based training sessions on a mannequin, along with knowledge of POCUS, can assist neonatologists and paediatricians for a quick and appropriate response in this emergency condition.

Outcomes of patients with gallbladder cancer presenting with acute cholecystitis.

The main purpose of this study is to explore the outcomes of patients found to have gallbladder cancer during investigation and diagnosis of acute cholecystitis. The incidence of primary gallbladder cancer co-existing in acute cholecystitis is not well defined in the literature, with anecdotal reports suggesting that they experience worse outcomes than patients with gallbladder cancer found incidentally. METHODS: A retrospective review of all patients with gallbladder cancer managed at the Canberra Health Service between 1998 and May 2022 were identified and reviewed. RESULTS: A total of 65 patients were diagnosed with primary gallbladder cancer during the study period with a mean age of 70.4 years (SD 11.4, range 59-81.8 years) and a female preponderance (74% versus 26%) with a ratio of 2.8. Twenty (31%) patients presented with acute calculus cholecystitis and were found to have a primary gallbladder cancer. This group of patients were older and predominantly female, but the difference was not statistically significant. The overall 5-year survival in the cohort was 20% (stage 1 63%, stage 2 23%, stage 3 16%, and stage 4 0%). There was no statistically significant difference in survival between those who presented with acute cholecystitis vs other presentations. CONCLUSIONS: A third of the patients with gallbladder cancer presented with acute cholecystitis. There was no statistically significant difference in survival in those with bile spillage during cholecystectomy as well those presenting with acute cholecystitis.

An Expedition on Synthetic Methodology of FDA-approved Anticancer Drugs (2018-2021).

New drugs being established in the market every year produce specified structures for selective biological targeting. With medicinal insights into molecular recognition, these begot molecules open new rooms for designing potential new drug molecules. In this review, we report the compilation and analysis of a total of 56 drugs including 33 organic small molecules (Mobocertinib, Infigratinib, Sotorasib, Trilaciclib, Umbralisib, Tepotinib, Relugolix, Pralsetinib, Decitabine, Ripretinib, Selpercatinib, Capmatinib, Pemigatinib, Tucatinib, Selumetinib, Tazemetostat, Avapritinib, Zanubrutinib, Entrectinib, Pexidartinib, Darolutamide, Selinexor, Alpelisib, Erdafitinib, Gilteritinib, Larotrectinib, Glasdegib, Lorlatinib, Talazoparib, Dacomitinib, Duvelisib, Ivosidenib, Apalutamide), 6 metal complexes (Edotreotide Gallium Ga-68, fluoroestradiol F-18, Cu 64 dotatate, Gallium 68 PSMA-11, Piflufolastat F-18, 177Lu (lutetium)), 16 macromolecules as monoclonal antibody conjugates (Brentuximabvedotin, Amivantamab-vmjw, Loncastuximabtesirine, Dostarlimab, Margetuximab, Naxitamab, Belantamabmafodotin, Tafasitamab, Inebilizumab, SacituzumabGovitecan, Isatuximab, Trastuzumab, Enfortumabvedotin, Polatuzumab, Cemiplimab, Mogamulizumab) and 1 peptide enzyme (Erwiniachrysanthemi-derived asparaginase) approved by the U.S. FDA between 2018 to 2021. These drugs act as anticancer agents against various cancer types, especially non-small cell lung, lymphoma, breast, prostate, multiple myeloma, neuroendocrine tumor, cervical, bladder, cholangiocarcinoma, myeloid leukemia, gastrointestinal, neuroblastoma, thyroid, epithelioid and cutaneous squamous cell carcinoma. The review comprises the key structural features, approval times, target selectivity, mechanisms of action, therapeutic indication, formulations, and possible synthetic approaches of these approved drugs. These crucial details will benefit the scientific community for futuristic new developments in this arena.

Identification of dysregulation of sphingolipids in retinoblastoma using liquid chromatography-mass spectrometry.

Retinoblastoma (RB) is a rare ocular cancer seen in children that counts for approximately 3% of all childhood cancers. It is found that mutation in RB1, a tumour Suppressor Gene on chromosome 13 as the cause of malignancy. Retinoblastoma protein is the target for ceramide to cause apoptosis. We studied lipidomics of two RB cell lines, one aggressive cell line (NCC-RbC-51) derived from a metastatic site and one non aggressive cell line (WERI-Rb1) in comparison with a control cell line (MIO-M1). Lipid profiles of all the cell lines were studied using high resolution mass spectrometer coupled to high performance liquid chromatography. Data acquired from all the three cell lines in positive mode were analyzed to identify differentially expressed metabolites. Several phospholipids and lysophospholipids were found to be dysregulated. We observed upregulation of hexosyl ceramides, and down regulation of dihydroceramides and higher order sphingoglycolipids hinting at a hindered sphingolipid biosynthesis. The results obtained from liquid chromatography-mass spectrometry are validated by using qPCR and it was observed that genes involved in ceramide biosynthesis pathway are getting down regulated.

Management of rectal cancer in the era of total neoadjuvant therapy and watch and wait: A multidisciplinary team discussion at the Australasian Gastro-Intestinal Trials Group (AGITG) Annual Scientific Meeting 2022.

Rectal cancer is a common malignancy. The management of rectal cancer has recently evolved and has undergone a paradigm shift with the advent of treatment approaches such as total neoadjuvant therapy and the watch-and-wait approach. However, despite the recently available evidence, there is no consensus on the optimal management approach in the setting of locally advanced rectal cancer. To address some of the controversies, a joint multidisciplinary panel discussion was conducted at the Australasian Gastro-Intestinal Trials Group (AGITG) Annual Scientific Meeting in November 2022. Members from different subspecialties formed two panels and discussed three clinical cases in a debate format. Each case represented some of the complex issues faced by clinicians in this setting. The discussion is now presented in this manuscript, which depicts the different available management approaches and reiterates the importance of a multidisciplinary approach.

Standard Versus Modified Ipilimumab, in Combination With Nivolumab, in Advanced Renal Cell Carcinoma: A Randomized Phase II Trial (PRISM).

PURPOSE: Ipilimumab (IPI), in combination with nivolumab (NIVO), is an approved frontline treatment option for patients with intermediate- or poor-risk advanced renal cell carcinoma (aRCC). We conducted a randomized phase II trial to evaluate whether administering IPI once every 12 weeks (modified), instead of once every 3 weeks (standard), in combination with NIVO, is associated with a favorable toxicity profile. METHODS: Treatment-naïve patients with clear-cell aRCC were randomly assigned 2:1 to receive four doses of modified or standard IPI, 1 mg/kg, in combination with NIVO (3 mg/kg). The primary end point was the proportion of patients with a grade 3-5 treatment-related adverse event (trAE) among those who received at least one dose of therapy. The key secondary end point was 12-month progression-free survival (PFS) in the modified arm compared with historical sunitinib control. The study was not designed to formally compare arms for efficacy. RESULTS: Between March 2018 and January 2020, 192 patients (69.8% intermediate/poor-risk) were randomly assigned and received at least one dose of study drug. The incidence of grade 3-5 trAEs was significantly lower among participants receiving modified versus standard IPI (32.8% v 53.1%; odds ratio, 0.43 [90% CI, 0.25 to 0.72]; P = .0075). The 12-month PFS (90% CI) using modified IPI was 46.1% (38.6 to 53.2). At a median follow-up of 21 months, the overall response rate was 45.3% versus 35.9% and the median PFS was 10.8 months versus 9.8 months in the modified and standard IPI groups, respectively. CONCLUSION: Rates of grade 3-5 trAEs were significantly lower in patients receiving modified versus standard IPI. Although 12-month PFS did not meet the prespecified efficacy threshold compared with historical control, informal comparison of treatment groups did not suggest any reduction in efficacy with the modified schedule.

Localized and regulated peptide pigment formation inside liquid droplets through confined enzymatic oxidation.

Melanin pigments are found in most life forms, where they are responsible for coloration and ultraviolet (UV) light protection. Natural melanin is a poorly soluble and complex biosynthesis product produced through confined and templated enzymatic oxidation of tyrosine. It has been challenging to create water-soluble synthetic mimics. This study demonstrates the enzymatic synthesis of oxidized phenols confined inside liquid droplets. We use an amphiphilic, bifunctional peptide, DYFR9, that combines a tyrosine tripeptide previously shown to undergo enzymatic oxidation to form peptide pigments with broad absorbance, and polyarginine to facilitate complex coacervation in the presence of ATP. When ATP, DYFR9 are mixed and exposed to tyrosinase, pigmented liquid droplets result, while no appreciable oxidation is observed in the bulk.