Dense Fiber Network Research Articles

Multifunctional polymeric nanocapsules with enhanced cartilage penetration and retention for osteoarthritis treatment

Osteoarthritis (OA) is a prevalent joint disease characterized by cartilage degeneration and subchondral bone homeostasis imbalance. Effective topical OA therapy is challenging, as therapeutic drugs often suffer from insufficient penetration and rapid clearance. We develop miniature polydopamine (PDA) nanocapsules (sub-60 nm), which are conjugated with collagen-binding polypeptide (CBP) and loaded with an anabolic drug (i.e., parathyroid hormone 1–34, PTH 1–34) for efficient OA treatment. Such multifunctional polymeric nanocapsules, denoted as PDA@CBP-PTH, possess deformability when interacting with the dense collagen fiber networks, enabling the efficient penetration into 1 mm cartilage in 4 h and prolonged retention within the joints up to 28 days. Moreover, PDA@CBP-PTH nanocapsules exhibit excellent reactive oxygen species scavenging property in chondrocytes and enhance the anabolism in subchondral bone. The nanosystem, as dual-mode treatment for OA, demonstrates rapid penetration, long-lasting effects, and combinational therapeutic impact, paving the way for reversing the progression of OA for joint health care.

Super foldable transparent paper by regulating the multi-scale structure of cellulose fibers

Transparent cellulose papers have emerged as a promising substrate and/or functional component for next-generation sustainable flexible electronics. However, obtaining transparent paper with folding endurance comparable to that of plastic films such as polyethylene terephthalate (PET) remains a major challenge, which was addressed in this study by modulating the multiscale structure (from molecular structure, aggregation structure to fibrous morphology) of wood fibers. Compared to the natural wood fibers, the modified fibers not only retained their length and cellulose degree of polymerization (DP) to a large extent, but also had lower crystallinity and improved swelling capability, which well preserved the fiber strength and dense intertwined fiber network, and led to stronger inter-fiber interactions in the final transparent paper. The obtained paper (CM-paper) exhibits an optical transparency of 91 % and a folding endurance of 37,466 times, comparable to that of commercial PET (39,955 folds). Furthermore, the underlying mechanism for the superior foldability of the transparent paper was unveiled at three scales is explored. Finally, the potential application of CM-paper in electromagnetic induction electrodes was demonstrated, where the CM-paper electrodes exhibit satisfactory conductivity after repeated rubbing. This work offers an innovative approach to produce transparent papers with outstanding foldability, which is expected to plastic replacement.

Prevalence and Histological Study of Oestrus ovis Larvae in Slaughtered Goat of Babylon City, Iraq

This study was carried out to investigate the prevalence of larval stage Oestrus ovis conducted during the period from September 2023 to the end of March 2024 at Babylon city, Iraq. 250 goats firstly were examined grossly and postmortem by longitudinally cutting with a manual saw, secondly, the collected larvae (45) were examined microscopically to measure its length and overall morphology. The total infestation rate was 26% (65/250). The highest rate of infestation was in female which was 44/150 (29.3%) while in male the infestation rate was 21/100(21%). The rate of infestation increases with the progression age of animal, older adult (over three years) was more susceptible to infestation was recorded 30/85(35.3%), while 17% (14/80) were in ages less than one year. Therefore, it showed a highly significant difference at (P<0.01). Furthermore, the histopathological sections of nasal cavity showed that Numerous mucous glands, thickening of epithelium, hyperplasia of blood vessels and severe Infiltration of inflammatory in goat infected with O.ovis larvae. In contrast, the uninfected goat showed moderate inflammatory cell infiltration in mucosal layer of nasal cavity and several dense glandular aggregates encircled by a dense network of elastic fibers. In conclusion, this study shows the important of O. ovis that infect goat in Babylon city, Iraq. Moreover, the morphology of all larval stage is similar except their measurement, color, and the shape of respiratory spiracles.

Abstract C020: Unconvering the hidden immunosuppressive landscape in pancreatic ductal adenocarcinoma

Abstract Pancreatic ductal adenocarcinoma (PDA) is one of the deadliest forms of cancer with an extremely low survival rate. Despite the success of therapeutic T cells in hematologic cancers, many solid tumors, including PDA, remain unresponsive with such therapies, partly due to its mechanically complex, dense, and immunosuppressive stroma. Therefore, understanding the dynamic interplay between therapeutic T cells and the tumor microenvironment (TME) is crucial for revealing engineering targets for next-generation immunotherapies. We approach this problem with genetically engineered KPC (KrasLSL-G12D/+; Trp53LSL-R172H/+; Pdx-1-Cre) mouse models that recapitulates PDA disease progression and stromal dynamics. Within live tumor slices from primary tumors, we are defining how stromal components such as dense collagen fiber networks and tumor-associated macrophages (TAMs) orchestrate an immunosuppressive landscape. We employ multiphoton laser scanning microscopy (MPLSM) to generate multiphoton excitation of fluorescence (cell dyes and immunofluorescence) and second harmonic generation (SHG) for collagen fibers to acquire multidimensional data (x, y, z, c, t) of T cell migration and interaction within the TME. We subsequently reveal T cell migration and interaction as a function of its physical and biological ECM components using advanced computer vision and machine learning algorithms based on the Clustered Random Convolutional Kernel Transform (cROCKET), revealing a hidden landscape in the feature space. Perturbations to the TME in KPC mice with CCR2 inhibitor CCX598 (in vivo) and clodronate liposomes (ex vivo) deplete CD11b+ myeloid cells, resulting in altered behaviors of the infiltrating T cells. Anti-PD-1 monoclonal antibody neutralizes the PD-1/PD-L1 axis in T cells, resulting in enhanced migration and infiltration in tumor slices. Citation Format: Guhan Qian, Hongrong Zhang, Aine Knott, Jon Zettervall, Ingunn Stromnes, Paolo Provenzano. Unconvering the hidden immunosuppressive landscape in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr C020.

Review on Causes and Management of Ganglion Cyst after Anterior Cruciate Ligament Reconstruction

The gelatinous fluid within a ganglion is rich in hyaluronic acid and other mucopolysaccharides, and the lesion itself is surrounded by a dense network of collagen fibres and fibrocytes. By restoring knee stability, the procedure aims to enhance the patient’s quality of life. Historically, individuals who underwent anterior cruciate ligament (ACL) surgery were able to resume their prior level of athletic involvement in 75%–90% of cases. ACL ganglion cysts are associated with serious clinical symptoms. Some people’s discomfort and stiffness from immobility due to large ganglia prohibit them from fully extending. Such individuals should have an arthroscopy or a computed tomography (CT) scan to decompress the ganglion, which offers immediate relief. ACL surgeries are becoming more and more common, and ganglion cysts may be present in individuals who have pain at the extremes of both flexion and extension has a clinical history. Radiologists must be conversant with these therapies and the adverse effects that go with them. While arthroscopic treatment offers quick discomfort alleviation without compromising ligament integrity, when it comes to radiological diagnostics, nothing beats magnetic resonance imaging (MRI). With an MRI, any other relevant intraarticular abnormalities may be ruled out. Safe CT scan-guided suction was used to successfully cure this patient’s ACL ganglion cyst symptoms.

Collective Organization Behaviors of Multi‐Cell Systems Induced by Engineered ECM‐Cell Mechanical Coupling

AbstractCells in vivo are surrounded by fibrous extracellular matrix (ECM), which can mediate the propagation of active cellular forces through stressed fiber bundles and regulate various biological processes. However, the mechanisms for multi‐cellular organization and collective dynamics induced by cell‐ECM mechanical couplings, which are crucial for the development of novel ECM‐based biomaterial for cell manipulation and biomechanical applications, remain poorly understood. Herein, the authors design an in vitro quasi‐3D experimental system and demonstrate a transition between spreading and aggregating in collective organizational behaviors of discrete multi‐cellular systems, induced by engineered ECM‐cell mechanical coupling, with the observed phenomena and underlying mechanisms differing fundamentally from those of cell monolayers. During the process of collective cell organization, the collagen substrate undergoes reconstruction into a dense fiber network structure, which is correlated with local cellular density and consistent with observed enhanced cells' motility; and the weakening of fiber bundle formation within the hydrogel reduces cells’ movement. Moreover, cells can respond to the curvature and shape of the original cell population and form different aggregation patterns. These results elucidate important physical factors involved in collective cell organization and provide important references for potential applications of biomaterials in new therapies and tissue engineering.

Cell seeding via bioprinted hydrogels supports cell migration into porous apatite-wollastonite bioceramic scaffolds for bone tissue engineering

Cell seeding via cell-laden hydrogels offers a rapid way of depositing cells onto a substrate or scaffold. When appropriately formulated, hydrogels provide a dense network of fibres for cellular encapsulation and attachment, creating a protective environment that prevents cells to be washed away by media. However, when incorporating hydrogels into a cell seeding strategy the cellular capacity for migration from a hydrogel network and subsequent biofunctionality must be assessed. Here, we compare cell seeding via a bioprinted hydrogel with conventional manual cell seeding in media. To this end, we use a binder jet 3D printed bioceramic scaffold as a model system for bone tissue engineering and the reactive jet impingement (ReJI) bioprinting system to deliver high cell density cell-laden hydrogels onto the surface of the scaffolds. The bioceramic scaffolds were produced in apatite-wollastonite (AW) glass-ceramic, with a total porosity of ~50 %, with pore size predominantly around 50–200 μm. Bone marrow-derived mesenchymal stromal cells were seeded onto the porous AW substrate both in media and via ReJI bioprinting. Cell seeding in media confirmed the osteoinductive nature and the ability of the scaffold to support cell migration within the porous structure. Cell seeding via ReJI bioprinting demonstrated that the cell-laden hydrogel penetrated the porous AW structure upon hydrogel deposition. Furthermore, cells would then migrate out from the hydrogel network and interact with the bioceramic substrate. Overall, levels of cell migration and mineralisation were significant and comparable for both seeding approaches. However, cell seeding via bioprinted hydrogels may serve as an effective strategy for in situ cell seeding into implants, which is desired in clinical tissue engineering procedures, avoiding the time taken for cell attachment from media, and the requirement to maintain a specific orientation until attachment has occurred.

The interface design and properties enhancement of ZnO/cellulose composites: Branching fiber network to guide the assembly of ZnO flower

Using renewable biomass resources to regulate the growth and properties of catalysts is sustainable nanotechnology for achieving efficient photocatalysis and recycling. This work suggested a way to produce paper-based photocatalysts and resize the embedded zinc oxide (ZnO) flowers. The combination of experimental analysis and theoretical simulations demonstrated that small pores of the branching fiber network enhanced the interfacial interaction between ZnO flowers and cellulose fibers, thereby improving mechanical properties and optimizing flower structure. The interaction energy and electron density difference (EDD) simulation results demonstrated that the ZnO/cellulose interface structure shares significant attraction and charge transfer. Cellulose fibers ground for 20 cycles (CFG20) possessed dense branching fiber network and loaded with the smallest ZnO flowers, achieving a balance of strong mechanical properties and reaction efficiency. Remarkably, ZnO/CFG20 paper-based catalyst indicated strong photodegradation efficiency (100% for methyl orange, 100% for phenol, and 85.23% for aniline) and excellent reusability. This work will pave the way for the green regulation of catalysts.

An anti-inflammatory chondroitin sulfate-poly(lactic-co-glycolic acid) composite electrospinning membrane for postoperative abdominal adhesion prevention.

Postoperative abdominal adhesion is a very common and serious complication, resulting in pain, intestinal obstruction and heavy economic burden. Post-injury inflammation that could activate the coagulation cascade and deposition of fibrin is a major cause of adhesion. Many physical barrier membranes are used to prevent abdominal adhesion, but their efficiency is limited due to the lack of anti-inflammatory activity. Here, an electrospinning membrane composed of poly(lactic-co-glycolic acid) (PLGA) providing support and mechanical strength and chondroitin sulfate (CS) conferring anti-inflammation activity is fabricated for preventing abdominal adhesion after injury. The PLGA/CS membrane shows a highly dense fiber network structure with improved hydrophilicity and good cytocompatibility. Importantly, the PLGA/CS membrane with a mass ratio of CS at 20% provides superior anti-adhesion efficiency over a native PLGA membrane and commercial poly(D, L-lactide) (PDLLA) film in abdominal adhesion trauma rat models. The mechanism is that the PLGA/CS membrane could alleviate the local inflammatory response as indicated by the promoted percentage of anti-inflammatory M2-type macrophages and decreased expression of pro-inflammatory factors, such as IL-1β, TNF-α and IL-6, resulting in the suppression of the coagulation system and the activation of the fibrinolytic system. Furthermore, the deposition of fibrin at the abdominal wall was inhibited, and the damaged abdominal tissue was repaired with the treatment of the PLGA/CS membrane. Collectively, the PLGA/CS electrospinning membrane is a promising drug-/cytokine-free anti-inflammatory barrier for post-surgery abdominal adhesion prevention and a bioactive composite for tissue regeneration.

Ultraviolet Light Treatment of Titanium Microfiber Scaffolds Enhances Osteoblast Recruitment and Osteoconductivity in a Vertical Bone Augmentation Model: 3D UV Photofunctionalization

Vertical bone augmentation to create host bone prior to implant placement is one of the most challenging regenerative procedures. The objective of this study is to evaluate the capacity of a UV-photofunctionalized titanium microfiber scaffold to recruit osteoblasts, generate intra-scaffold bone, and integrate with host bone in a vertical augmentation model with unidirectional, limited blood supply. Scaffolds were fabricated by molding and sintering grade 1 commercially pure titanium microfibers (20 μm diameter) and treated with UVC light (200-280 nm wavelength) emitted from a low-pressure mercury lamp for 20 min immediately before experiments. The scaffolds had an even and dense fiber network with 87% porosity and 20-50 mm inter-fiber distance. Surface carbon reduced from 30% on untreated scaffold to 10% after UV treatment, which corresponded to hydro-repellent to superhydrophilic conversion. Vertical infiltration testing revealed that UV-treated scaffolds absorbed 4-, 14-, and 15-times more blood, water, and glycerol than untreated scaffolds, respectively. In vitro, four-times more osteoblasts attached to UV-treated scaffolds than untreated scaffolds three hours after seeding. On day 2, there were 70% more osteoblasts on UV-treated scaffolds. Fluorescent microscopy visualized confluent osteoblasts on UV-treated microfibers two days after seeding but sparse and separated cells on untreated microfibers. Alkaline phosphatase activity and osteocalcin gene expression were significantly greater in osteoblasts grown on UV-treated microfiber scaffolds. In an in vivo model of vertical augmentation on rat femoral cortical bone, the interfacial strength between innate cortical bone and UV-treated microfiber scaffold after two weeks of healing was double that observed between bone and untreated scaffold. Morphological and chemical analysis confirmed seamless integration of the innate cortical and regenerated bone within microfiber networks for UV-treated scaffolds. These results indicate synergy between titanium microfiber scaffolds and UV photofunctionalization to provide a novel and effective strategy for vertical bone augmentation.

Tooth-Derived Matrix Granules for Enhanced Bone Healing: Chemical Composition, Morphological Aspects, and Clinical Outcomes

Bone grafting has increasingly been used in surgical procedures for enhanced bone augmentation. Tooth-derived graft material has received considerable attention due to its chemical composition and autogenous source that can improve bone tissue healing. The main aim of this study was to provide a short and comprehensive review on the chemical composition, morphological aspects, and clinical outcomes of bone grafting using tooth-derived matrix granules. Dentin tissue has a chemical composition similar to that on bone tissues regarding the presence of hydroxyapatite, type I collagen, and different growth factors. Dentin-matrix granules are often processed at well-controlled size ranging from approximately 300 up to 1300 µm, while maintaining porosity and organic content. In addition, a dense collagen fiber network is still present after the milling and chemical treatment of dentin granules. Thus, dentin-matrix granules can improve the bone healing process considering their chemical composition, porous structure, and adequate size. However, further in vivo and in vitro studies should be performed taking into consideration different demineralization procedures, remnant organic content, porosity, and granule size.

Structural connectivity of the ANT region based on human ex-vivo and HCP data. Relevance for DBS in ANT for epilepsy

ObjectiveDeep Brain Stimulation (DBS) in the Anterior Nucleus of the Thalamus (ANT) has been shown to be a safe and efficacious treatment option for patients with Drug-Resitant focal Epilepsy (DRE). The ANT has been selected frequently in open and controlled studies for bilateral DBS. There is a substantial variability in ANT-DBS outcomes which is not fully understood. These outcomes might not be explained by the target location alone but potentially depend on the connectivity of the mere stimulation site with the epilepsy onset-associated brain regions. The likely sub-components of this anatomy are fiber pathways which penetrate or touch the ANT region and constitute a complex and dense fiber network which has not been described so far. A detailed characterization of this ANT associated fiber anatomy may therefore help to identify which areas are associated with positive or negative outcomes of ANT-DBS. Furthermore, prediction properties in individual ANT-DBS cases might be tested. In this work we aim to generate an anatomically detailed map of candidate fiber structures which might in the future lead to a holistic image of structural connectivity of the ANT region. MethodsTo resolve the various components of the complex fiber network connected to the ANT we used a synthetic pathway reconstruction method that combines anatomical fiber tracking with dMRI-based tractography and iteratively created an anatomical high-resolution fiber map representing the most important bundles related to the ANT. ResultsThe anatomically detailed 3D representation of the fibers in the ANT region generated with the synthetic pathway reconstruction method incorporates multiple anatomically defined fiber bundles with their course, orientation, connectivity and relative strength. Distinctive positions within the ANT region have a different hierarchical profile with respect to the stimulation-activated fiber bundles. This detailed connectivity map, which is embedded into the topographic map of the MNI brain, provides novel opportunities to analyze the outcomes of the ANT-DBS studies. ConclusionOur synthetic reconstruction method provides the first anatomically realistic fiber pathway map in the human ANT region incorporating histological and structural MRI data. We propose that this complex ANT fiber network can be used for detailed analysis of the outcomes of DBS studies and potentially for visualization during the stimulation planning procedures. The connectivity map might also facilitate surgical planning and will help to simulate the complex ANT connectivity. Possible activation patterns that may be elicited by electrodes in different positions in the ANT region will help to understand clinically diverse outcomes based on this new dense fiber network map. As a consequence this work might in the future help to improve individual outcomes in ANT-DBS.

Polycaprolactone/Polylactic Acid Membrane Fails to Prevent Laminectomy-induced Sprouting of CGRP- and SP-immunopositive Nerve Fibres in the Dura mater lumbalis of Rats.

Mechanisms and prevention of failed back surgery syndromes are rarely known in the clinical context. It has been shown that laminectomy induces outgrowth of putative nociceptive peptidergic afferents in the dura mater lumbalis of rats. We aimed to investigate whether the application of a polycaprolactone/polylactic acid membrane (Mesofol) after surgery inhibits sensory hyperinnervation. Adult Lewis rats were assigned to three groups: Control (no manipulation), Laminectomy and Laminectomy + Mesofol. Six weeks post-surgery, the durae were removed, immunohistochemically stained for CGRP- and SP-positive afferents and their density quantified. In controls, CGRP- and SP-positive neurons were predominantly found in ventral but rarely observed in dorsal parts of the dura. Following laminectomy, the density of afferents significantly increased ventrally, resulting in a dense network of nerve fibers. In dorsal regions, neuronal sprouting of was observed. Covering the dura with Mesofol after laminectomy had no impact on nerve fibre outgrowth. Application of Mesofol neither prevents nor significantly diminishes the laminectomy-induced increase in the density of peptidergic afferents.

Electrochemical investigation of carbon paper/ZnO nanocomposite electrodes for capacitive anion capturing

In this work, we demonstrate an effective anion capturing in an aqueous medium using a highly porous carbon paper decorated with ZnO nanorods. A sol–gel technique was first employed to form a thin and compact seed layer of ZnO nanoparticles on the dense network of carbon fibers in the carbon paper. Subsequently, ZnO nanorods were successfully grown on the pre-seeded carbon papers using inexpensive chemical bath deposition. The prepared porous electrodes were electrochemically investigated for improved charge storage and stability under long-term operational conditions. The results show effective capacitive deionization with a maximum areal capacitance of 2 mF/cm2, an energy consumption of 50 kJ per mole of chlorine ions, and an excellent long-term stability of the fabricated C-ZnO electrodes. The experimental results are supported by COMSOL simulations. Besides the demonstrated capacitive desalination application, our results can directly be used to realize suitable electrodes for energy storage in supercapacitors.

Microporous Formation Mechanism of Biaxial Stretching PA6/PP Membranes with High Porosity and Uniform Pore Size Distribution.

The low porosity and wide pore size distribution of biaxial stretching PP microporous membranes continue to be the primary impediments to their industrial application. To solve this problem, there is a critical and urgent need to study the micropore-forming mechanism of PP membranes. In this research, the interfacial micropore formation mechanism of PA6/PP membranes during biaxial stretching was investigated. PA6/PP membranes containing spherical PA6 and fibrillar PA6 were found to exhibit different interfacial micropore formation mechanisms. Numerous micropores were generated in the PA6/PP membranes, containing PA6 spherical particles via the interface separation between the PP matrix and PA6 spherical particles during longitudinal stretching. Subsequent transverse stretching further expanded the two-phase interface, promoting the breakdown and fibrosis of the PP matrix and forming a spider-web-like microporous structure centered on spherical PA6 particles. In PA6/PP membranes with PA6 fibers, fewer micropores were generated during longitudinal stretching, but the subsequent transverse stretching violently separated the PA6 fibers, resulting in a dense fiber network composed of PA6 fibers interwoven with PP fibers. Crucially, the PA6/PP biaxial stretching of microporous membranes presented an optimized pore structure, higher porosity, narrower pore size distribution, and better permeability than β-PP membranes. Furthermore, this study explored a new approach to the fabrication of high-performance PA6/PP microporous membranes, with good prospects for potential industrial application.

Cytology and histology characteristics of platelet-rich fibrin

Background: Platelet-rich fibrin (PRF) is a biomaterial whose frame is a network of fibrin fibers containing cells from peripheral blood and growth factors. PRF biomaterials have great potential for application in regenerative medicine, especially in maxillofacial surgery and orthopedic trauma. The purpose of this study is to investigate the cytological and histological properties of PRF in order to provide the background knowledge for the applied studies of PRF. Materials and Methods: Peripheral blood from 10 rabbits collected via the ear artery was used to generate platelet-rich plasma and platelet-rich fibrin. Blood samples with anticoagulant are centrifuged to obtain fractions of platelet-rich plasma (PRP) and Platelet rich and white blood cell rich plasma (L-PRP). Plasma is fibrinated with Calcium chloride (CaCl2) to produce platelet-rich fibrin (PRF), Platelet rich and white blood cell rich fibrin (L-PRF). The cellular composition of PRP and L-PRP was investigated using an automated veterinary hematology analyzer. The histological structures of PRF and L-PRF were examined by Hematoxylin-Eosin and Sirius Red staining. Results: The results of cell composition showed that PRP almost did not contain cellular components such as white blood cells and red blood cells, and the platelet concentration was lower than that of peripheral blood. Meanwhile, L-PRP contains a large number of cellular components, especially a high density of white blood cells and platelets. Histological examination results showed that PRF had a dense network of fibrin fibers and lacked the presence of cells. Conclusions: The PRF and L-PRF biomaterials have a suitable spatial structure as a natural biological substrate. Furthermore, L-PRF has a rich cellular component that has great potential in promoting tissue regeneration Key words: Biomaterials, Platelet-rich plasma (PRP), platelet rich and white blood cell rich plasma (L-PRP), tissue regenerative medicine, histological structure

Reusability of P3 Facial Filter in a Pandemic Emergency: A 3D Analysis of Filter Microstructure with X-ray Microtomography Images after Dry Heat and UV Sterilization Procedures.

Objective: Our goal is to evaluate the effects of heat and ultraviolet (UV) irradiation on P3 facial respirator microstructure. Intervention: P3 facial filters were exposed to dry heat and UV sterilization procedures. Methods: P3 facial filter samples underwent a standardized sterilization process based on dry heat and UV irradiation techniques. We analyzed critical parameters of internal microstructure, such as fiber thickness and porosity, before and after sterilization, using 3D data obtained with synchrotron radiation-based X-ray computed microtomography (micro-CT). The analyzed filter has two inner layers called the “finer” and “coarser” layers. The “finer” layer consists of a dense fiber network, while the “coarser” layer has a less compact fiber network. Results: Analysis of 3D images showed no statistically significant differences between the P3 filter of the controls and the dry heat/UV sterilized samples. In particular, averages fiber thickness in the finer layer of the control and the 60° dry heated and UV-irradiated sample groups was almost identical. Average fiber thickness for the coarser layer of the control and the 60° dry heated and UV-irradiated sample groups was very similar, measuring 19.33 µm (±0.47), 18.33 µm (±0.47), and 18.66 µm (±0.47), respectively. There was no substantial difference in maximum fiber thickness in the finer layers and coarser layers. For the control group samples, maximum thickness was on average 11.43 µm (±1.24) in the finer layer and 59.33 µm (±6.79) in the coarser layer. Similarly, the 60° dry heated group samples were thickened 12.2 µm (±0.21) in the finer layer and 57.33 µm (±1.24) in the coarser layer, while for the UV-irradiated group, the mean max thickness was 12.23 µm (±0.90) in the finer layer and 58.00 µm (±6.68) in the coarser layer. Theoretical porosity analysis resulted in 74% and 88% for the finer and coarser layers. The finer layers’ theoretical porosity tended to decrease in dry heat and UV-irradiated samples compared with the respective control samples. Conclusions: Dry heat and UV sterilization processes do not substantially alter the morphometry of the P3 filter samples’ internal microstructure, as studied with micro-CT. The current study suggests that safe P3 filter facepiece reusability is theoretically feasible and should be further investigated.

Oligosarcomas, IDH-mutant are distinct and aggressive

Oligodendrogliomas are defined at the molecular level by the presence of an IDH mutation and codeletion of chromosomal arms 1p and 19q. In the past, case reports and small studies described gliomas with sarcomatous features arising from oligodendrogliomas, so called oligosarcomas. Here, we report a series of 24 IDH-mutant oligosarcomas from 23 patients forming a distinct methylation class. The tumors were recurrences from prior oligodendrogliomas or developed de novo. Precursor tumors of 12 oligosarcomas were histologically and molecularly indistinguishable from conventional oligodendrogliomas. Oligosarcoma tumor cells were embedded in a dense network of reticulin fibers, frequently showing p53 accumulation, positivity for SMA and CALD1, loss of OLIG2 and gain of H3K27 trimethylation (H3K27me3) as compared to primary lesions. In 5 oligosarcomas no 1p/19q codeletion was detectable, although it was present in the primary lesions. Copy number neutral LOH was determined as underlying mechanism. Oligosarcomas harbored an increased chromosomal copy number variation load with frequent CDKN2A/B deletions. Proteomic profiling demonstrated oligosarcomas to be highly distinct from conventional CNS WHO grade 3 oligodendrogliomas with consistent evidence for a smooth muscle differentiation. Expression of several tumor suppressors was reduced with NF1 being lost frequently. In contrast, oncogenic YAP1 was aberrantly overexpressed in oligosarcomas. Panel sequencing revealed mutations in NF1 and TP53 along with IDH1/2 and TERT promoter mutations. Survival of patients was significantly poorer for oligosarcomas as first recurrence than for grade 3 oligodendrogliomas as first recurrence. These results establish oligosarcomas as a distinct group of IDH-mutant gliomas differing from conventional oligodendrogliomas on the histologic, epigenetic, proteomic, molecular and clinical level. The diagnosis can be based on the combined presence of (a) sarcomatous histology, (b) IDH-mutation and (c) TERT promoter mutation and/or 1p/19q codeletion, or, in unresolved cases, on its characteristic DNA methylation profile.

The pigment-dispersing factor neuronal network systematically grows in developing honey bees.

The neuropeptide pigment-dispersing factor (PDF) plays a prominent role in the circadian clock of many insects including honey bees. In the honey bee brain, PDF is expressed in about 15 clock neurons per hemisphere that lie between the central brain and the optic lobes. As in other insects, the bee PDF neurons form wide arborizations in the brain, but certain differences are evident. For example, they arborize only sparsely in the accessory medulla (AME), which serves as important communication center of the circadian clock in cockroaches and flies. Furthermore, all bee PDF neurons cluster together, which makes it impossible to distinguish individual projections. Here, we investigated the developing bee PDF network and found that the first three PDF neurons arise in the third larval instar and form a dense network of varicose fibers at the base of the developing medulla that strongly resembles the AME of hemimetabolous insects. In addition, they send faint fibers toward the lateral superior protocerebrum. In last larval instar, PDF cells with larger somata appear and send fibers toward the distal medulla and the medial protocerebrum. In the dorsal part of the medulla serpentine layer, a small PDF knot evolves from which PDF fibers extend ventrally. This knot disappears during metamorphosis and the varicose arborizations in the putative AME become fainter. Instead, a new strongly stained PDF fiber hub appears in front of the lobula. Simultaneously, the number of PDF neurons increases and the PDF neuronal network in the brain gets continuously more complex.

Autonomously Propelled Colloids for Penetration and Payload Delivery in Complex Extracellular Matrices.

For effective treatment of diseases such as cancer or fibrosis, it is essential to deliver therapeutic agents such as drugs to the diseased tissue, but these diseased sites are surrounded by a dense network of fibers, cells, and proteins known as the extracellular matrix (ECM). The ECM forms a barrier between the diseased cells and blood circulation, the main route of administration of most drug delivery nanoparticles. Hence, a stiff ECM impedes drug delivery by limiting the transport of drugs to the diseased tissue. The use of self-propelled particles (SPPs) that can move in a directional manner with the application of physical or chemical forces can help in increasing the drug delivery efficiency. Here, we provide a comprehensive look at the current ECM models in use to mimic the in vivo diseased states, the different types of SPPs that have been experimentally tested in these models, and suggest directions for future research toward clinical translation of SPPs in diverse biomedical settings.