Remimazolam Preserves Oxygen Reserve and Improves Sedation Safety Compared to Propofol in Endoscopic Retrograde Cholangiopancreatography.

Background: Remimazolam is a short-acting benzodiazepine with less cardiorespiratory depression compared with propofol. The Oxygen Reserve Index (ORi) reflects oxygenation status in the mild hyperoxic range and can detect subtle respiratory depression induced by sedatives.

Objective: We compared remimazolam and propofol in patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) and assessed the ORi to evaluate the impact of these sedatives on oxygen reserve.

Early Positive Fluid Balance Associates with Increased Mortality in Neurological Critically Ill Patients: A 10-Year Cohort Study.

: Fluid management is a critical aspect of care for neurocritically ill patients, yet the optimal approach remains unclear. The relationship between fluid balance and clinical outcomes in these patients requires further investigation, particularly regarding the timing and volume of fluid administration. : This retrospective observational study analyzed 2186 adult patients admitted to the neurosurgical intensive care unit (ICU) from January 2013 to December 2022.

Aging-in-Place Challenges for Rural Older Adults: Responses from Service Providers.

Most rural older adults tend to age in place, highlighting the need for further study on aging-in-place (AIP) challenges faced by this aging cohort using reliable data sources. This qualitative study explored the challenges rural older adults experience when AIP, based on the perspectives of rural service providers. Sixteen face-to-face interviews were conducted with service providers at their service sites using a semi-structured questionnaire.

Therapeutic Potential of Santa Herba Extract in Obesity: Impact on Lipid Metabolism and Hormonal Balance.

Many studies have reported that flavonoids can effectively suppress metabolic diseases related to obesity. Santa Herba extract (SHE), which is rich in flavonoids, has shown potential anti-obesity effects through clinical evaluations, but its anti-obesity mechanisms remain unclear. Therefore, an obese mouse model was established to further investigate its underlying mechanisms and biological effects.

A highly mobile adeno-associated virus targeting vascular smooth muscle cells for the treatment of pulmonary arterial hypertension.

In pulmonary arterial hypertension (PAH), a phenotypic switch in pulmonary arterial smooth muscle cells (PASMCs) that is primarily caused by aberrant gene regulatory networks can lead to dysregulated vascular remodelling, heart failure or death. No curative therapies for PAH are currently available, presumably because of a lack of viral vectors specifically targeting PASMCs. Here we show that a highly mobile and PASMC-tropic adeno-associated virus variant developed via directed evolution overcomes physical barriers that inhibit its transfer from bronchial airways to vascular layers, ultimately boosting therapeutic efficacy in murine models of PAH.

Peptides From Animal and Fishery Byproducts: Uplifting the Functionality of Fifth Quarter.

The meat and fish sectors are primary sources of animal protein for human consumption. However, they also generate large volumes of byproducts and organic waste annually, posing major challenges in terms of sustainable disposal. These byproducts have the potential to be repurposed into high-value, low-volume products, such as bioactive peptides or hydrolysates.

Oxidative Stability of Novel Peptides (Linusorbs) in Flaxseed Meal-Fortified Gluten-Free Bread.

Flaxseed meal, rich in water-soluble gums, improves the texture of gluten-free (GF) products. Bioactive antioxidant peptides from flaxseed, known as linusorbs (LOs) or cyclolinopeptides, may provide health benefits. However, the stability of flaxseed-derived LOs during dough preparation, baking, and storage remains unclear.

Determining ED90 of Flumazenil for Selective Respiratory Distress Improvement Using Remimazolam During Endoscopic Submucosal Dissection of Gastric Neoplasms: A Prospective Study.

Background: Patients undergoing endoscopic submucosal dissection under monitored anesthesia care (MAC) with remimazolam may develop respiratory distress during the procedure. In these cases, low doses of flumazenil improved respiratory distress without completely reversing sedation, which is a novel phenomenon. This study aimed to explore the ED90 of flumazenil to selectively improve respiratory distress in patients with MAC treated with remimazolam.

Engineering of Saccharomyces cerevisiae as a platform strain for microbial production of sphingosine-1-phosphate.

Background: Sphingosine-1-phosphate (S1P) is a multifunctional sphingolipid that has been implicated in regulating cellular activities in mammalian cells. Due to its therapeutic potential, there is a growing interest in developing efficient methods for S1P production. To date, the production of S1P has been achieved through chemical synthesis or blood extraction, but these processes have limitations such as complexity and cost.

Effect of remimazolam on oxygen reserve compared with propofol during upper gastrointestinal endoscopy: Randomized controlled study.

Objectives: Propofol is commonly used for endoscopic sedation. However, it can induce adverse hemodynamic effects. Remimazolam is known to have a fast onset and short duration comparable to that of propofol, but with fewer effects on hemodynamics.

Effect of Gossypol on Gene Expression in Swine Granulosa Cells.

Gossypol (GP), a polyphenolic compound in cottonseed, has notable effects on female reproduction and the respiratory system in pigs. This study aimed to discern the alterations in gene expression within swine granulosa cells (GCs) when treated with two concentrations of GP (6.25 and 12.

Associations between Clinicopathological Characteristics and Intraoperative Opioid Requirements during Endoscopic Submucosal Dissection with Monitored Anesthesia Care: A Retrospective Study.

Endoscopic submucosal dissection is used to treat early gastric neoplasms. Compared with other endoscopic procedures, it requires higher doses of opioids, leading to adverse events during monitored anesthesia care. We investigated the correlations between clinicopathological characteristics and intraprocedural opioid requirements in patients who underwent endoscopic submucosal dissection under monitored anesthesia care.

Targeted protein degradation systems to enhance Wnt signaling.

Molecules that facilitate targeted protein degradation (TPD) offer great promise as novel therapeutics. The human hepatic lectin asialoglycoprotein receptor (ASGR) is selectively expressed on hepatocytes. We have previously engineered an anti-ASGR1 antibody-mutant RSPO2 (RSPO2RA) fusion protein (called SWEETS) to drive tissue-specific degradation of ZNRF3/RNF43 E3 ubiquitin ligases, which achieved hepatocyte-specific enhanced Wnt signaling, proliferation, and restored liver function in mouse models, and an antibody-RSPO2RA fusion molecule is currently in human clinical trials.

Design principles and therapeutic applications of novel synthetic WNT signaling agonists.

Wingless-related integration site or Wingless and Int-1 or Wingless-Int (WNT) signaling is crucial for embryonic development, and adult tissue homeostasis and regeneration, through its essential roles in cell fate, patterning, and stem cell regulation. The biophysical characteristics of WNT ligands have hindered efforts to interrogate ligand activity and prevented their development as therapeutics. Recent breakthroughs have enabled the generation of synthetic WNT signaling molecules that possess characteristics of natural ligands and potently activate the pathway, while also providing distinct advantages for therapeutic development and manufacturing.

Effects of Fc glycosylation on the activity of WNT mimetic agonistic antibodies.

Monoclonal antibodies have been explored in a broad range of applications including receptor agonism. Given the importance of receptor conformation in signaling, the agonistic activity of antibodies that engage these receptors are influenced by many parameters. Tetravalent bispecific antibodies that target the frizzled and lipoprotein receptor-related protein receptors and subsequently activate WNT ("Wingless-related integration site" or "Wingless and Int-1" or "Wingless-Int") signaling have been constructed.

Correction: Mohd Azmi et al. Application of Plant Proteases in Meat Tenderization: Recent Trends and Future Prospects. 2023, , 1336.

In the original publication [...

BRAIDing receptors for cell-specific targeting.

Systemic toxicity is a major challenge in the development of therapeutics. Consequently, cell-type-specific targeting is needed to improve on-target efficacy while reducing off-target toxicity. Here, we describe a cell-targeting system we have termed BRAID (idged ctivation by ntra/intermolecular ivision) whereby an active molecule is divided into two inactive or less active parts that are subsequently brought together via a so-called 'bridging receptor' on the target cell.

Short-term Efficacy and Safety of Intravitreal Brolucizumab Injection for Treatment-Naive Exudate Age-related Macular Degeneration: A Multicenter Study.

Purpose: To compare short-term efficacy and safety of intravitreal brolucizumab injection with aflibercept in treatment-naive neovascular age-related macular degeneration (nAMD) patients.

Methods: A total of 59 eyes from 59 treatment-naive nAMD patients in three hospitals were retrospectively reviewed. Of which, 27 patients underwent intravitreal brolucizumab injections and 32 received aflibercept.

Grasping through dynamic weaving with entangled closed loops.

Pick-and-place is essential in diverse robotic applications for industries including manufacturing, and assembly. Soft grippers offer a cost-effective, and low-maintenance alternative for secure object grasping without complex sensing and control systems. However, their inherent softness normally limits payload capabilities and robustness to external disturbances, constraining their applications and hindering reliable performance.

Comparison of patient experiences and clinical outcomes between an illuminated chopper and a conventional chopper under a surgical microscope.

Purpose: To compare patient experiences and cooperation and the clinical outcomes illuminated chopper vs conventional chopper during cataract surgery.

Setting: 4 tertiary institutions in Korea.

Design: Prospective, randomized, paired-eye, controlled pilot study.

Novel Frizzled-specific antibody-based Wnt mimetics and Wnt superagonists selectively activate WNT/β-catenin signaling in target tissues.

WNTs are essential factors for stem cell biology, embryonic development, and for maintaining homeostasis and tissue repair in adults. Difficulties in purifying WNTs and their lack of receptor selectivity have hampered research and regenerative medicine development. While breakthroughs in WNT mimetic development have overcome some of these difficulties, the tools developed so far are incomplete and mimetics alone are often not sufficient.

Therapeutic blood-brain barrier modulation and stroke treatment by a bioengineered FZD-selective WNT surrogate in mice.

Derangements of the blood-brain barrier (BBB) or blood-retinal barrier (BRB) occur in disorders ranging from stroke, cancer, diabetic retinopathy, and Alzheimer's disease. The Norrin/FZD/TSPAN12 pathway activates WNT/β-catenin signaling, which is essential for BBB and BRB function. However, systemic pharmacologic FZD stimulation is hindered by obligate palmitoylation and insolubility of native WNTs and suboptimal properties of the FZD-selective ligand Norrin.

Distinguishing between DNA-Loaded Full and Empty Capsids of Adeno-Associated Virus with Atomic Force Microscopy Imaging.

Recently, miraculous therapy approaches involving adeno-associated virus (AAV) for incurable diseases such as spinal muscular atrophy and inherited retinal dysfunction have been introduced. Nonreplicative, nonpathogenic, low rates of chromosome insertional properties and the existence of neutralizing antibodies are main safety reasons why the FDA approved its use in gene delivery. To date, AAV production always results in a mixture of nontherapeutic (empty) and therapeutic (DNA-loaded) full capsids (10-98%).

EGT022, an RGD-containing recombinant disintegrin, inhibits the VEGF-induced angiogenic process by targeting integrin β3 in endothelial cells.

Objectives: EGT022, an RGD-containing recombinant disintegrin from human ADAM metallopeptidase domain 15 (ADAM15), has been reported to stimulate vascular maturation of retinal blood vessels with promotion of pericyte coverage through binding to integrin αIIbβ3. Previous studies have reported that angiogenesis can be inhibited by several RGD motif-containing disintegrins; however, the effect of EGT022 on Vascular endothelial growth factor (VEGF)-induced angiogenesis has not yet been determined. This study was conducted in order to evaluate the anti-angiogenic function of EGT022 in VEGF-induced endothelial cells.

Application of Plant Proteases in Meat Tenderization: Recent Trends and Future Prospects.

Papain, bromelain, and ficin are commonly used plant proteases used for meat tenderization. Other plant proteases explored for meat tenderization are actinidin, zingibain, and cucumin. The application of plant crude extracts or powders containing higher levels of compounds exerting tenderizing effects is also gaining popularity due to lower cost, improved sensory attributes of meat, and the presence of bioactive compounds exerting additional benefits in addition to tenderization, such as antioxidants and antimicrobial effects.