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Background and Objectives: Only a few different approaches are currently utilized for saphenous nerve block. Our study aimed to compare two different ultrasound (US)-guided saphenous nerve blocks and designed this study to test the hypothesis that the medial infracondylar approach has more success rate than the subsartorial approach applied in saphenous nerve blockage. Methods: The study included 76 patients (18–65 years old) with the American Society of Anesthesiologists physical status of I–III, who were scheduled for below-knee surgery by the orthopedics clinic. The patients who underwent US-guided saphenous nerve blockade were randomly divided into two groups: Group S (subsartorial approach) and Group M (medial infracondylar approach). For all patients who had a block procedure, the pinprick test was performed using a blunt needle on the saphenous nerve dermatome. Success rate, time of block performance (TBP), onset time of block (OTB), and duration of sensory blockade (DSB) were recorded using a patient follow-up form. Results: The US-guided saphenous nerve block success rate was similar (88% vs. 91%) or both techniques. The DSB values were 415.2 ± 65.3 min (95% confidence interval [CI]: 286.3–539.8) for Group S and 369.7 ± 52.2 min (95% CI: 265.6–467.8) for Group M (P = 0.04), and no significant differences in the TBP and OTB were observed between the groups. Conclusion: Both of the different anatomical approaches have equally high success rates. Although the DSB was found to be significantly longer in the subsartorial approach, this is clinically unimportant, and the medial infracondylar approach is still a viable alternative technique during saphenous nerve blockage.

Novel segmented poly(urethaneurea) elastomers (TPUU) were prepared through the reaction of poly(tetramethylene oxide)glycols (PTMO-1000 and PTMO-2000) with excess aromatic diisocyanates (TDI and MDI), followed by in situchain extension with water, through the formation of urea linkages. High molecular weight TPUU polymers with high urea hard segment (HS) contents of up to 44% by weight were obtained. FTIR analysis of the carbonyl region clearly showed the presence of strongly hydrogen bonded urethane and urea groups in the system. Dynamic mechanical analysis indicated the formation of microphase separated morphologies with well-defined PTMO glass transitions, followed by a composition dependent rubbery plateau extending well beyond 200 °C. Tapping mode AFM studies clearly indicated the formation of microphase morphology with hard urea domains dispersed or percolated through soft polyether matrix. Stress−strain tests demonstrated the formation of very strong elastomers with tensile strengths of up to 50 MPa. Tensile properties also showed a strong dependence on the soft segment molecular weight, structure of the diisocyanate used and HS content of the copolymer. [ABSTRACT FROM AUTHOR]

An aseptic abscess (AA) is an auto-inflammatory disorder characterized by necrotic lymph nodes and internal organ abscesses, most frequently located in the spleen. Described herein are two cases of aseptic abscesses; one in a patient with Behçet's disease and the other in a patient with mesenteric panniculitis.

Cellular growth and organismal development are remarkably complex processes that require the nutrient-responsive kinase mechanistic target of rapamycin complex 1 (mTORC1). Anticipating that important mTORC1 functions remained to be identified, we employed genetic and bioinformatic screening in C. elegans to uncover mechanisms of mTORC1 action. Here, we show that during larval growth, nutrients induce an extensive reprogramming of gene expression and alternative mRNA splicing by acting through mTORC1. mTORC1 regulates mRNA splicing and the production of protein-coding mRNA isoforms largely independently of its target p70 S6 kinase (S6K) by increasing the activity of the serine/arginine-rich (SR) protein RSP-6 (SRSF3/7) and other splicing factors. mTORC1-mediated mRNA splicing regulation is critical for growth; mediates nutrient control of mechanisms that include energy, nucleotide, amino acid, and other metabolic pathways; and may be conserved in humans. Although mTORC1 inhibition delays aging, mTORC1-induced mRNA splicing promotes longevity, suggesting that when mTORC1 is inhibited, enhancement of this splicing might provide additional anti-aging benefits., Competing Interests: Declaration of interests M.C.H. is a member of the scientific advisory board of Alixia Therapeutics., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Feature detection and matching are fundamental components in computer vision, underpinning a broad spectrum of applications. This study offers a comprehensive evaluation of traditional feature detections and descriptors, analyzing methods such as Scale Invariant Feature Transform (SIFT), Speeded-Up Robust Features (SURF), Binary Robust Independent Elementary Features (BRIEF), Oriented FAST and Rotated BRIEF (ORB), Binary Robust Invariant Scalable Keypoints (BRISK), KAZE, Accelerated KAZE (AKAZE), Fast Retina Keypoint (FREAK), Dense and Accurate Invariant Scalable descriptor for Yale (DAISY), Features from Accelerated Segment Test (FAST), and STAR. Each feature extractor was assessed based on its architectural design and complexity, focusing on how these factors influence computational efficiency and robustness under various transformations. Utilizing the Image Matching Challenge Photo Tourism 2020 dataset, which includes over 1.5 million images, the study identifies the FAST algorithm as the most efficient detector when paired with the ORB descriptor and Brute-Force (BF) matcher, offering the fastest feature extraction and matching process. ORB is notably effective on affine-transformed and brightened images, while AKAZE excels in conditions involving blurring, fisheye distortion, image rotation, and perspective distortions. Through more than 2 million comparisons, the study highlights the feature extractors that demonstrate superior resilience across various conditions, including rotation, scaling, blurring, brightening, affine transformations, perspective distortions, fisheye distortion, and salt-and-pepper noise., Competing Interests: The authors declare that they have no competing interests., (© 2024 ISIK.)

Herpes simples virus 1 (HSV-1) keratitis is a major cause of blindness globally. During primary infection, HSV-1 travels to the trigeminal ganglia and establishes lifelong latency. Although some treatments can reduce symptom severity and recurrence, there is no cure for HSV-1 keratitis. We used CRISPR-Cas9 to co-target gene sequences encoding two essential HSV-1 proteins, ICP0 and ICP27, as a potential therapy for HSV-1 keratitis. In HSV-1-infected Vero cells, the HSV-1 viral load and titer were significantly reduced by plasmid transfection or AAV2 vector transduction expressing Cas9 nuclease from Staphylococcus aureus (SaCas9) and paired guide RNAs (gRNAs). Off-target assessment showed minimal off-target editing activity from the selected gRNAs. We then tested our CRISPR-Cas9 gene editing approach in a latent rabbit model of HSV-1 keratitis. Corneal scarification with all-in-one AAV8(Y733F)-SaCas9 or AAV9-SaCas9 vector reduced viral shedding by over 50%. Interestingly, intravenous administration of the same AAV9-SaCas9 vector eliminated viral shedding in 92% of treated eyes. In addition, treated trigeminal ganglia showed a reduction in HSV-1 DNA and RNA expression. Our results support the utility of single-dose AAV9 all-in-one CRISPR-Cas9 gene editing as a safe and effective strategy for treating HSV-1 keratitis., Competing Interests: N.A., K.L., M.I., J.G., and G.-X.R. are employees of Excision BioTherapeutics. K.K. is a co-founder, board member, scientific advisor, and holds equity in Excision BioTherapeutics. The authors have filed a patent application related to this work., (© 2024 The Authors.)

Opioids can be used for medical and non-medical purposes. Chronic pain such as cancer, as well as the frequent use of such drugs in places such as operating rooms and intensive care units, and in non-medical areas like drug abuse the effects and side effects of these drugs need to be examined in more detail. For this purpose, the effects of fentanyl and remifentanil drugs on neuroinflammation, oxidative stress and cholinesterase metabolism were investigated. Neuron cells (CRL-10742) were used for the evaluation of the toxicity of fentanyl and remifentanil. MTT, PON1 activity and total thiol levels for its effect on oxidative stress, AChE and BChE activities for its effect on the cholinergic system, and TNF, IL-8 and IL-10 gene levels for its neuroinflammation effect were determined. The highest neurotoxic dose of fentanyl and remifentanil was determined as 10 μg/mL. It was observed that the rate of neuron cells in this dose has decreased by up to 61.80% and 56.89%, respectively. The IL-8 gene expression level in both opioids was down-regulated while IL 10 gene level was up-regulated in a dose-dependent manner compared to the control. In our results, the TNF gene expression level differs between the two opioids. In the fentanyl group, it was seen to be up-regulated in a dose-dependent manner compared to the control. Fentanyl and remifentanil showed an inhibitory effect against PON1, while remifentanil showed an increase in total thiol levels. PON1, BChE and total thiol activities showed similarity with MTT., (© 2024 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

This study aimed to investigate the effects of nanoparticles on macrophage polarization and their subsequent influence on post-tumorigenic behavior. Initially, seven different nanoparticles were applied to macrophages, and Zn-Ni-FeO (100 nm) and palladium nanoparticles (PdNPs, ∼25 nm) were found to induce M1-polarization in macrophages. A co-culture experiment was then conducted to examine the effects of macrophages on MCF-7 breast cancer micro-tissues. The M2-macrophages promoted tumor proliferation, while M1- and PdNPs-induced macrophages showed anti-tumor effects by suppressing cell proliferation. To reveal the mechanisms of effect, exosomes isolated from M1 (M1-Exo), M0 (M0-Exo), M2 (M2-Exo), and PdNPs-induced (PdNPs-Exo) macrophages were applied to the heterotypic tumor micro-tissues including MCF-7, human umbilical vein endothelial cells (HUVECs), and primary human dermal fibroblasts (phDFs). M2-Exo was seen to promote the migration of cancer cells and induce epithelial-mesenchymal transition (EMT), while M1-Exo suppressed these behaviors. PdNPs-Exo was effective in suppressing the aggressive nature of breast cancer cells similar to M1-Exo, moreover, the efficacy of 5-fluorouracil (5-FU) was increased in combination with PdNPs-Exo in both MCF-7 and heterotypic micro-tissues. In conclusion, PdNPs-Exo has potential anti-tumor effects, can be used as a combination therapy to enhance the efficacy of anti-cancer drugs, as well as innovative implants for breast cancer treatment.

Organoids are an emerging technology with great potential in human disease modelling, drug development, diagnosis, tissue engineering, and regenerative medicine. Organoids as 3D-tissue culture systems have gained special attention in the past decades due to their ability to faithfully recapitulate the complexity of organ-specific tissues. Despite considerable successes in culturing physiologically relevant organoids, their real-life applications are currently limited by challenges such as scarcity of an appropriate biomimetic matrix. Peptide amphiphiles (PAs) due to their well-defined chemistry, tunable bioactivity, and extracellular matrix (ECM)-like nanofibrous architecture represent an attractive material scaffold for organoids development. Using cerebral organoids (COs) as exemplar, we demonstrate the possibility to create bio-instructive hydrogels with tunable stiffness ranging from 0.69 kPa to 2.24 kPa to culture and induce COs growth. We used orthogonal chemistry involving oxidative coupling and supramolecular interactions to create two-component hydrogels integrating the bio-instructive activity and ECM-like nanofibrous architecture of a laminin-mimetic PAs (IKVAV-PA) and tunable crosslinking density of hyaluronic acid functionalized with tyramine (HA-Try). Multi-omics technology including transcriptomics, proteomics, and metabolomics reveals the induction and growth of COs in soft HA-Tyr hydrogels containing PA-IKVAV such that the COs display morphology and biomolecular signatures similar to those grown in Matrigel scaffolds. Our materials hold great promise as a safe synthetic ECM for COs induction and growth. Our approach represents a well-defined alternative to animal-derived matrices for the culture of COs and might expand the applicability of organoids in basic and clinical research. STATEMENT OF SIGNIFICANCE: Synthetic bio-instructive materials which display tissue-specific functionality and nanoscale architecture of the native extracellular matrix are attractive matrices for organoids development. These synthetic matrices are chemically defined and animal-free compared to current gold standard matrices such as Matrigel. Here, we developed hydrogel matrices with tunable stiffness, which incorporate laminin-mimetic peptide amphiphiles to grow and expand cerebral organoids. Using multi-omics tools, the present study provides exciting data on the effects of neuro-inductive cues on the biomolecular profiles of brain organoids., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Fossil mollusc shells are used for dating geological materials because they are well preserved throughout geological time. In this study, the radicals in the structure of fossil mollusc shells (Dreissena iconica, Valvata piscinalis, Bithynia tentaculate, Unio pictorum) collected from the Eastern Part of Old Konya Lake in Türkiye were investigated by EPR technique. For all fossil shells, microwave and temperature dependence of the signals were examined, and the signals suitable for dating are discussed. Characteristic features of intrinsic and impurity-related radicals were identified and the importance of paleontological evaluation of molluscs to get a reliable equivalent dose in EPR dating studies was emphasised., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

3D printing offers an exciting opportunity to fabricate biological constructs with specific geometries, clinically relevant sizes, and functions for biomedical applications. However, successful application of 3D printing is limited by the narrow range of printable and bio-instructive materials. Multicomponent hydrogel bioinks present unique opportunities to create bio-instructive materials able to display high structural fidelity and fulfill the mechanical and functional requirements for in situ tissue engineering. Herein, 3D printable and perfusable multicomponent hydrogel constructs with high elasticity, self-recovery properties, excellent hydrodynamic performance, and improved bioactivity are reported. The materials' design strategy integrates fast gelation kinetics of sodium alginate (Alg), in situ crosslinking of tyramine-modified hyaluronic acid (HAT), and temperature-dependent self-assembly and biological functions of decellularized aorta (dAECM). Using extrusion-based printing approach, the capability to print the multicomponent hydrogel bioinks with high precision into a well-defined vascular constructs able to withstand flow and repetitive cyclic compressive loading, is demonstrated. Both in vitro and pre-clinical models are used to show the pro-angiogenic and anti-inflammatory properties of the multicomponent vascular constructs. This study presents a strategy to create new bioink whose functional properties are greater than the sum of their components and with potential applications in vascular tissue engineering and regenerative medicine., (© 2023 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.)

Temporal cue analysis in auditory stimulus is essential in the perception of speech sounds. The effect of transcranial direct current stimulation (tDCS) on auditory temporal processing remains unclear. In this study, we examined whether tDCS applied over the left auditory cortex (AC) has a polarity-specific behavioral effect on the categorical perception of speech sounds whose temporal features are modulated. Sixteen healthy volunteers in each group were received anodal, cathodal, or sham tDCS. A phonetic categorization task including auditory stimuli with varying voice onset time was performed before and during tDCS, and responses were analyzed. No statistically significant difference was observed between groups (anode, cathode, sham) and within the groups (pre-tDCS, during tDCS) in comparisons of the slope parameter of the identification function obtained from the phonetic categorization task data. Our results show that a single-session application of tDCS over the left AC does not significantly affect the categorical perception of speech sounds., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

This work presents a polysaccharide and protein-based two-component hybrid hydrogel integrating the cell-adhesive gelatin-tyramine (G-Tyr) and nonadhesive hyaluronic acid-tyramine (HA-Tyr) through enzyme-mediated oxidative coupling reaction. The resulting HA-Tyr/G-Tyr hydrogel reflects the precise chemical and mechanical features of the cancer extracellular matrix and is able to tune cancer cell adhesion upon switching the component ratio. The cells form quasi-spheroids on HA-Tyr rich hydrogels, while they tend to form an invasive monolayer culture on G-Tyr rich hydrogels. The metastatic genotype of colorectal adenocarcinoma cells (HT-29) increases on G-Tyr rich hydrogels which is driven by the material's adhesive property, and additionally confirmed by the suppressed gene expressions of apoptosis and autophagy. On the other hand, HA-Tyr rich hydrogels lead the cells to necrotic death via oxidative stress in quasi-spheroids. This work demonstrates the ideality of HA-Tyr/G-Tyr to modulate cancer cell adhesion, which also has potential in preventing primary metastasis after onco-surgery, biomaterials-based cancer research, and drug testing.

Recent research effort in biomaterial development has largely focused on engineering bio-instructive materials to stimulate specific cell signaling. Assessing the biological performance of these materials using time-consuming and trial-and-error traditional low-throughput screening techniques remains a critical challenge in the field. In contrast, the use of increasingly sophisticated omics technologies to facilitate high-throughput screening of unbiased global understanding of cell-biomaterial interactions at gene, epigenetic, mRNA, protein, metabolite, and lipid levels holds great potential to predict the therapeutic outcome of biomaterials with specific properties. In this review, we highlight the potential use of omics technologies - namely transcriptomics, proteomics, metabolomics and lipidomics - in biomaterial design and deciphering of the fundamental cell behaviors ( e.g. , adhesion, migration, differentiation) in response to cell-biomaterial interactions. Moreover, the potential challenges and prospects of high-throughput analysis platforms are discussed rationally, providing an insight into the developing field and its use in biomaterials science.

Peptic ulcer is a gastric or duodenal mucosal injury; psychological stress may participate in development of the lesions. Heat shock protein-70 (HSP70) is a molecular chaperone that is responsible for cellular healing; it is an early biomarker of cellular damage. Nitric oxide (NO) is an intra- and intercellular messenger in the gastrointestinal system that protects mucosal integrity. Lactobacillus rhamnosus is among the microflora of the intestinal tract; it is resistant to gastric acidity. We investigated the efficacy of L. rhamnosus administration on ulcer pathogenesis, stress protein HSP70 and NO levels in experimental stress induced ulcer. The proton pump inhibitor, pantoprazole, was used for comparison with the gastroprotective effect of the probiotic. We administered 10 mg/kg pantoprazole and L. rhamnosus at doses of 3 × 10 8  cfu/ml (M1), 15 × 10 8  cfu/ml (M5), 30 × 10 8  cfu/ml (M10) to rats according to McFarland-1, McFarland-5, McFarland-10 standards, respectively. Rats were stressed by immobilization at 4 °C, then sacrificed. The pH, amounts of gastric mucus, NO and HSP70 levels were measured and the histological structure of stomach was assessed. We found increased NO levels in the M5 group and increased HSP70 expression in the pantoprazole group. Significant epithelial damage was observed in the stressed groups and minimal epithelial damage was observed in M5 group compared to controls. The probiotic, L. rhamnosus , may be useful for preventing stress induced ulcers.

Extracellular nanovesicles, particularly exosomes, can deliver their diverse bioactive biomolecular content, including miRNAs, proteins, and lipids, thus providing a context for investigating the capability of exosomes to induce stem cells toward lineage-specific cells and tissue regeneration. In this study, it is demonstrated that rat subventricular zone neural stem cell-derived exosomes (rSVZ-NSCExo) can control neural-lineage specification of human mesenchymal stem cells (hMSCs). Microarray analysis shows that the miRNA content of rSVZ-NSCExo is a faithful representation of rSVZ tissue. Through immunocytochemistry, gene expression, and multi-omics analyses, the capability to use rSVZ-NSCExo to induce hMSCs into a neuroglial or neural stem cell phenotype and genotype in a temporal and dose-dependent manner via multiple signaling pathways is demonstrated. The current study presents a new and innovative strategy to modulate hMSCs fate by harnessing the molecular content of exosomes, thus suggesting future opportunities for rSVZ-NSCExo in nerve tissue regeneration., (© 2022 Wiley-VCH GmbH.)

Manipulation of energy-dissipating adipocytes has the potential to produce metabolic benefits. To this end, it is valuable to understand the mechanisms controlling the generation and function of thermogenic fat. Here, we identify Letm1 domain containing 1 (Letmd1) as a regulator of brown fat formation and function. The expression of Letmd1 is induced in brown fat by cold exposure and by β-adrenergic activation. Letmd1-deficient mice exhibit severe cold intolerance concomitant with abnormal brown fat morphology, reduced thermogenic gene expression, and low mitochondrial content. The null mice exhibit impaired β3-adrenoreceptor-dependent thermogenesis and are prone to diet-induced obesity and defective glucose disposal. Letmd1 was previously described as a mitochondrial protein, and we find that it also localizes to the nucleus and interacts with the transcriptional coregulator and chromatin remodeler Brg1/Smarca4, thus providing a way to impact thermogenic gene expression. Our study uncovers a role for Letmd1 as a key regulatory component of adaptive thermogenesis., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Self-assembling bio-instructive materials that can provide a biomimetic tissue microenvironment with the capability to regulate cellular behaviors represent an attractive platform in regenerative medicine. Herein, we develop a hybrid neuro-instructive hydrogel that combines the properties of a photo-crosslinkable gelatin methacrylate (GelMA) and self-assembling peptide amphiphiles (PAs) bearing a laminin-derived neuro-inductive epitope (PA-GSR). Electrostatic interaction and ultraviolet light crosslinking mechanisms were combined to create dual-crosslinked hybrid hydrogels with tunable stiffness. Spectroscopic, microscopic and theoretical techniques show that the cationic PA-GSR(+) electrostatically co-assembles with the negatively charged GelMA to create weak hydrogels with hierarchically ordered microstructures, which were further photo-crosslinked to create mechanically robust hydrogels. Dynamic oscillatory rheology and micromechanical testing show that photo-crosslinking of the co-assembled GelMA and PA-GSR(+) hydrogel results in robust hydrogels displaying improved stiffness. Gene expression analysis was used to show that GelMA/PA-GSR(+) hydrogels can induce human mesenchymal stem cells (hMSCs) into neural-lineage cells and supports neural-lineage specification of neuroblast-like cells (SH-SY5Y) in a growth-factor-free manner. Also, metabolomics analysis suggests that the hydrogel alters the metabolite profiles in the cells by affecting multiple molecular pathways. This work highlights a new approach for the design of PA-based hybrid hydrogels with robust mechanical properties and biological functionalities for nerve tissue regeneration.