Slow Degradation Research Articles

ArcKR expression modifies synaptic plasticity following epileptic activity: Differential effects with invitro and invivo seizure-induction protocols.

Pathological forms of neural activity, such as epileptic seizures, modify the expression pattern of multiple proteins, leading to persistent changes in brain function. One such protein is activity-regulated cytoskeleton-associated protein (Arc), which is critically involved in protein-synthesis-dependent synaptic plasticity underlying learning and memory. In the present study, we have investigated how the expression of ArcKR, a form of Arc in which the ubiquitination sites have been mutated, resulting in slowed Arc degradation, modifies group I metabotropic glutamate receptor-mediated long-term depression (G1-mGluR-LTD) following seizures. We used a knock-in mice line that express ArcKR and two hyperexcitation models: an invitro model, where hippocampal slices were exposed to zero Mg2+, 6 mM K+; and an invivo model, where kainic acid was injected unilaterally into the hippocampus. In both models, field excitatory postsynaptic potentials (fEPSPs) were recorded from the CA1 region of hippocampal slices in response to Schaffer collateral stimulation and G1-mGluR-LTD was induced chemically with the group 1 mGluR agonist DHPG. In the invitro model, ArcKR expression enhanced the effects of seizure activity and increased the magnitude of G1-mGluR LTD, an effect that could be blocked with the mGluR5 antagonist MTEP. In the invivo model, fEPSPs were significantly smaller in slices from ArcKR mice and were less contaminated by population spikes. In this model, the amount of G1-mGluR-LTD was significantly less in epileptic slices from ArcKR mice as compared to wildtype (WT) mice. We have shown that expression of ArcKR, a form of Arc in which degradation is reduced, significantly modulates the magnitude of G1-mGluR-LTD following epileptic seizures. However, the effect of ArcKR on LTD depends on the epileptic model used, with enhancement of LTD in an invitro model and a reduction in the kainate mouse model.

Circular economy approach to recycling of high-density polyethylene (HDPE) for the production of pet products

The generation of waste remains a constant in anthropogenic activities, particularly inorganic waste, which poses significant threats to living organisms due to its slow degradation in the environment. This study, conducted in Zamora, Michoacán, Mexico, proposes the recycling of high-density polyethylene (HDPE) within a circular economy framework, reintroducing this waste as raw material for new processes to produce pet products. The objective is to generate positive environmental impacts by reducing inorganic solid waste, social impacts by providing the population with new pet products, and economic impacts by reusing inert HDPE material. An experimental design with an artisanal basis was employed, generating empirical knowledge and applying critical thinking to validate the results. The study successfully produced a range of pet products, including identification tags and food and water containers, achieving a categorization of these products. The results presented in this paper are expected to be a practical contribution to sustainable development and recycling discussion, a necessary task for the green growth of economies, especially in developing countries.

Injectable and high-strength PLGA/CPC loaded ALN/MgO bone cement for bone regeneration by facilitating osteogenesis and inhibiting osteoclastogenesis in osteoporotic bone defects

Osteoporosis (OP) can result in slower bone regeneration than the normal condition due to the imbalance between osteogenesis and osteoclastogenesis, making osteoporotic bone defects healing a significant clinical challenge. Calcium phosphate cement (CPC) is a promising bone substitute material due to its good osteoinductive activity, however, the drawbacks such as fragility, slow degradation rate and incapability to control bone loss restrict its application in osteoporotic bone defects treatment. Currently, we developed the PLGA electrospun nanofiber sheets to carry alendronate (ALN) and magnesium oxide nanoparticle (nMgO) into CPC, therefore, to obtain a high-strength bone cement (C/AM-PL/C). The C/AM-PL/C bone cement had high mechanical strength, anti-washout ability, good injection performance and drug sustained release capacity. More importantly, the C/AM-PL/C cement promoted the osteogenic differentiation of bone marrow mesenchymal stem cells and neovascularization via the release of Mg2+ (from nMgO) and Ca2+ (during the degradation of CPC), and inhibited osteoclastogenesis via the release of ALN in vitro. Moreover, the injection of C/AM-PL/C cement significantly improved bone healing in an OP model with femur condyle defects in vivo. Altogether, the injectable C/AM-PL/C cement could facilitate osteoporotic bone regeneration, demonstrating its capacity as a promising candidate for treatment of osteoporotic bone defects.

Utilizing PET bottles for sustainable cellular reinforcement: A study on enhancing fly ash backfill bearing strength with innovative geocell alternative

The slow degradation rate is one of the major global concerns. Only, 60 % produced is being recycled. Among these waste materials, Polyethylene Terephthalate (PET) bottles contribute around 10 % to the total plastic waste produced. The recycling process of PET bottles considering existing capacity in environmentally responsible ways is limited. It is estimated that 60 % of PET bottles produced are being disposed of in landfills. To overcome this, past studies have suggested novel approaches for using it as substitute for conventional geocell as soil reinforcement and stability. However, past studies mostly focused on application of PET bottles as flaked, shreds and sliced form. The present study attempts on application of PET bottles under fly ash (FA) backfills without mechanical alterations. Full-scale experiments were conducted on FA backfill system, for both unreinforced and reinforced conditions. A comparative study was performed between high-density polyethylene (HDPE) geocell and PET bottle mattress to assess the bearing strength of the FA backfill. Experiments were performed in a 1 m3 tank with a loading plate width of 200 mm. Vertical loading was applied onto the backfill footing (for all the trial series), till the footing settlement of 40 mm is achieved. An aspect ratio of 2 was considered for HDPE geocell and PET bottles. Rock quarry dust (RQD) was considered as cell infill and overlay material on FA backfill. The test results showed that settlement accumulation rate was low under reinforced scenario compared to the unreinforced condition, with higher resilient (elastic) settlement. RQD over the PET-reinforced zone was also seen to have enhanced the load distribution aspect, thereby reducing deformation in PET reinforcement. This usage of waste material will contribute towards sustainable development. This work demonstrates the feasibility and effectiveness of PET reinforcement to be used as replacement for HDPE geocell, which eventually can agument the design methodology of structural backfills.

Cerium-oxide functionalized iron scaffolds: A synergistic approach for enhanced degradation and reduced cytotoxicity

Biodegradable scaffolds play a crucial role in biomedical restoration. These are three-dimensional (3D) structures that can provide support for the development of newly formed bone tissues. Among the studied metallic biodegradable scaffolds, those composed of iron (Fe) are notable for their high mechanical resistance. However, the slow degradation rate of Fe and the potential cytotoxicity of its degradation products pose challenges to effective osseointegration. Cerium oxide was incorporated into Fe scaffolds to overcome these two inherent limitations.We employed the dynamic hydrogen bubbling template (DHBT) technique, utilizing a citric acid-based electrolyte, to produce iron scaffolds. This same technique was used to embed cerium oxide nanoparticles (CNFe), whereas electrodeposition was used to create a thin cerium oxide coating over the scaffolds (CCFe). The oxidation state of cerium oxide in the functionalized scaffolds was scrutinized through surface characterization techniques. Ensuring similar porosities, we evaluated the degradation of the different distinct scaffolds using electrochemical techniques.The impact of cerium incorporation within or over the scaffolds on their degradation and cell viability was correlated with cerium oxidation states and the nature of the resulting degradation products. The synergistic implications of adding cerium to the iron scaffolds were thoroughly explored, and their potential benefits in future clinical settings were discussed.

TRIM37 is a primate-specific E3 ligase for Huntingtin and accounts for the striatal degeneration in Huntington's disease.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease characterized by preferential neuronal loss in the striatum. The mechanism underlying striatal selective neurodegeneration remains unclear, making it difficult to develop effective treatments for HD. In the brains of nonhuman primates, we examined the expression of Huntingtin (HTT), the gene responsible for HD. We found that HTT protein is highly expressed in striatal neurons due to its slow degradation in the striatum. We also identified tripartite motif-containing 37 (TRIM37) as a primate-specific protein that interacts with HTT and is selectively reduced in the primate striatum. TRIM37 promotes the ubiquitination and degradation of mutant HTT (mHTT) in vitro and modulates mHTT aggregation in mouse and monkey brains. Our findings suggest that nonhuman primates are crucial for understanding the mechanisms of human diseases such as HD and support TRIM37 as a potential therapeutic target for treating HD.

How Per- and Poly-Fluoroalkyl Substances Affect Gamete Viability and Fertilization Capability: Insights from the Literature.

There has been emerging research linking per- and poly-fluoroalkyl substances (PFAS) to gamete viability and fertility. PFAS, prevalent in the environment and water supplies, undergo slow degradation due to their C-F bond and a long half-life (2.3-8.5 years). In females, PFAS inhibit the hypothalamic-pituitary-gonadal (HPG) axis, reducing follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, leading to the inhibition of androgen and estradiol production. PFAS have been found to cause detrimental effects on egg quality through impairing folliculogenesis. In males, PFAS can impair sperm motility and morphology: two fundamental qualities of successful fertilization. PFAS exposure has been proven to inhibit testosterone production, sperm capacitation, and acrosomal reaction. After fertilization, the results of PFAS exposure to embryos have also been investigated, showing reduced development to the blastocyst stage. The aim of this review is to report the main findings in the literature on the impact of PFAS exposure to gamete competency and fertilization capability by highlighting key studies on both male and female fertility. We report that there is significant evidence demonstrating the negative impacts on fertility after PFAS exposure. At high doses, these environmentally abundant and widespread compounds can significantly affect human fertility.

Pre-Steady-State and Steady-State Kinetic Analysis of Butyrylcholinesterase-Catalyzed Hydrolysis of Mirabegron, an Arylacylamide Drug.

The β-adrenergic drug Mirabegron, a drug initially used for the treatment of an overactive bladder, has new potential indications and is hydrolyzed by butyrylcholinesterase (BChE). This compound is one of the only arylacylamide substrates to be catabolized by BChE. A steady-state kinetic analysis at 25 °C and pH 7.0 showed that the enzyme behavior is Michaelian with this substrate and displays a long pre-steady-state phase characterized by a burst. The induction time, τ, increased with substrate concentration (τ ≈ 18 min at maximum velocity). The kinetic behavior was interpreted in terms of hysteretic behavior, resulting from a slow equilibrium between two enzyme active forms, E and E'. The pre-steady-state phase with the highest activity corresponds to action of the E form, and the steady state corresponds to action of the E' form. The catalytic parameters were determined as kcat = 7.3 min-1 and Km = 23.5 μM for the initial (burst) form E, and kcat = 1.6 min-1 and Km = 3.9 μM for the final form E'. Thus, the higher affinity of E' for Mirabegron triggers the slow enzyme state equilibrium toward a slow steady state. Despite the complexity of the reaction mechanism of Mirabegron with BChE, slow BChE-catalyzed degradation of Mirabegron in blood should have no impact on the pharmacological activities of this drug.

Development of alginate and alginate sulfate/polycaprolactone nanoparticles for growth factor delivery in wound healing therapy

Connective tissue growth factor (CTGF) holds great promise for enhancing the wound healing process; however, its clinical application is hindered by its low stability and the challenge of maintaining its effective concentration at the wound site. Herein, we developed novel double-emulsion alginate (Alg) and heparin-mimetic alginate sulfate (AlgSulf)/polycaprolactone (PCL) nanoparticles (NPs) for controlled CTGF delivery to promote accelerated wound healing. The NPs’ physicochemical properties, cytocompatibility, and wound healing activity were assessed on immortalized human keratinocytes (HaCaT), primary human dermal fibroblasts (HDF), and a murine cutaneous wound model. The synthesized NPs had a minimum hydrodynamic size of 200.25 nm. Treatment of HaCaT and HDF cells with Alg and AlgSulf2.0/PCL NPs did not show any toxicity when used at concentrations <50 µg/mL for up to 72 h. Moreover, the NPs’ size was not affected by elevated temperatures, acidic pH, or the presence of a protein-rich medium. The NPs have slow lysozyme-mediated degradation implying that they have an extended tissue retention time. Furthermore, we found that treatment of HaCaT and HDF cells with CTGF-loaded Alg and AlgSulf2.0/PCL NPs, respectively, induced rapid cell migration (76.12% and 79.49%, P<0.05). Finally, in vivo studies showed that CTGF-loaded Alg and AlgSulf2.0/PCL NPs result in the fastest and highest wound closure at the early and late stages of wound healing, respectively (36.49%, P<0.001 on day 1; 90.45%, P<0.05 on day 10), outperforming free CTGF. Double-emulsion NPs based on Alg or AlgSulf represent a viable strategy for delivering heparin-binding GF and other therapeutics, potentially aiding various disease treatments.

The role of plant extracts in the complex therapy of diseases of the musculoskeletal system

Medicinal plants and their secondary metabolites are increasingly used in the treatment of diseases in complex therapy. Inflammation is a pathological condition that includes a wide range of diseases such as rheumatic and immune-mediated conditions, diabetes, cardiovascular diseases, etc. Three plants are presented in the review: Harpgophytum procumbens, Curcuma longa, Bosswellia serrata, whose anti-inflammatory effects have been evaluated in clinical and experimental research. The use of Harpgophytum, turmeric and boswellia shows that these phytochemicals can directly act on multiple inflammatory mechanisms and may reduce pain and slow cartilage degradation in patients with osteoarthritis. Since treating inflammation is not a onedimensional remedy, we attempted to describe a multidimensional therapeutic approach to inflammation using phytoextracts. However, further research is needed to provide more information about the effectiveness of herbal extracts, as well as their combinations, in people with inflammatory joint diseases.

Effect of pH and temperature on tropane alkaloids within a processing strategy to provide safe infant cereal-based food

Tropane alkaloids (TAs) are secondary metabolites from weeds that can contaminate cereals and vegetables during harvest. Due to their toxicity, the Regulation (EC) 2023/915 sets maximum levels for atropine and scopolamine in cereal-based foods for infants containing millet, sorghum, buckwheat or their derived products. The aim of this study was to evaluate the effect of pH and temperature on the stability of TAs, as possible parameters in thermal processing to mitigate this chemical hazard in cereal-based infant food. The effect of pH (4 and 7) and temperature (80 °C and 100 °C) was assessed in buffer solutions. Also, treatment at 180 °C was performed in spiked and naturally incurred millet flour to assess the effect of high temperature, simulating cooking or drying, on the stability of TAs in the cereal matrix. The fate of 24 TAs was assessed by UHPLC-MS/MS. TAs showed high thermostability, although it was variable depending on the specific compound, pH, temperature and treatment time. In buffer solutions, higher degradation was found at 100 °C and pH 7. In spiked millet flour at 180 °C for 10 min, scopolamine and atropine contents decreased by 25 % and 22 %, similarly to other TAs which also showed a slow thermal degradation. Atropine, scopolamine, anisodamine, norscopolamine, scopine and scopoline were found in naturally contaminated millet flour. Interestingly, naturally incurred atropine was more thermostable than when spiked, showing a protective effect of the cereal matrix on TAs degradation. The present results highlight the need for an accurate monitorization of TAs in raw materials, as this chemical hazard may remain in infant cereal-based food even after intense thermal processing.

A Biodegradable Nano-Drug Delivery Platform for Co-Delivery of Minocycline and Chitosan to Achieve Efficient and Safe Non-Surgical Periodontitis Therapy.

Mesoporous silica nanoparticles (MSN) are widely used as ideal nanovehicles for the delivery of chemotherapeutic drugs. However, the balance between high anti-periodontitis activity and low biotoxicity has been challenging to maintain in most relevant studies owing to the slow degradation of silica in living organisms. In this study, -responsive hydroxyapatite (HAP) was doped into the MSN skeleton, and the chemotherapeutic drug minocycline hydrochloride (MH) was loaded into the pores of MSN, forming a negatively charged drug delivery system. Cationic chitosan (COS) is a biodegradable material with high antibacterial performance and good biosafety. In this study, COS was immobilized on the surface of the drug-loaded particles through stable charge interaction to construct a composite drug delivery system (MH@MSNion@COS). In vitro and cellular experiments demonstrated effective degradation of the nanocarrier system and synchronized controlled release of the drug. Notably, compared with single MH administration, this system, in which MH and COS jointly regulated the expression levels of periodontitis- associated inflammatory factors (TNF-α, IL-6, IL-1β, and iNOS), better inhibited the progress of periodontitis and induced tissue regeneration without showing significant toxic side effects in cells. This system provides a promising strategy for the design of intelligent, efficient, and safe anti-periodontitis drug delivery systems.

Surface Modification of Nano-Hydroxyapatite/Polymer Composite for Bone Tissue Repair Applications: A Review.

Nano-hydroxyapatite (n-HA) is the main inorganic component of natural bone, which has been widely used as a reinforcing filler for polymers in bone materials, and it can promote cell adhesion, proliferation, and differentiation. It can also produce interactions between cells and material surfaces through selective protein adsorption and has therefore always been a research hotspot in orthopedic materials. However, n-HA nano-particles are inherently easy to agglomerate and difficult to disperse evenly in the polymer. In addition, there are differences in trace elements between n-HA nano-particles and biological apatite, so the biological activity needs to be improved, and the slow degradation in vivo, which has seriously hindered the application of n-HA in bone fields, is unacceptable. Therefore, the modification of n-HA has been extensively reported in the literature. This article reviewed the physical modification and various chemical modification methods of n-HA in recent years, as well as their modification effects. In particular, various chemical modification methods and their modification effects were reviewed in detail. Finally, a summary and suggestions for the modification of n-HA were proposed, which would provide significant reference for achieving high-performance n-HA in biomedical applications.

The action of heated RC joints strengthened with a novel strategy combined CFRP and SSEMSM under a quasi-static cyclic load

The current work presents the application of a novel strategy for strengthening heated beam column (B-C) joints under a quasi-static cyclic load. This technique involves utilizing a layer of carbon fiber-reinforced polymers (CFRP) sheets with a layer of stainless-steel expanded metal sheet mesh (SSEMSM). These two layers are installed on the steel reinforcement cage inside the joint before concrete casting. Then the reinforced concrete B-C joints, after being cast and cured, were subjected to heat (i.e., 400 °C and 600 °C). The joints were divided into three groups: three joints were kept as is (i.e., reference joints; no strengthening was applied), whereas three joints were strengthened with the previously mentioned strategy. With a view to investigating the seismic behavior of RC joints, a quasi-static cyclic load was applied to the joints to simulate a seismic load. Results showed that the average maximum load capacity for upgraded joints (strengthened) increased by 30%, 19%, and 1% at ambient (i.e., 23 °C), 400 °C, and 600 °C temperatures, respectively, with respect to the reference joint (JCTA). More importantly, the experimental results reveal a significant increase in the cyclic response of strengthened joints (i.e., higher load capacity, greater displacement, higher dissipated energy, higher ductility, and slower degradation in the secant stiffness).

Fully bio-based intumescent flame retardant hybrid: A green strategy towards reducing fire hazard and improving degradation of polylactic acid

Polylactic acid (PLA) is a promising renewable polymer material with excellent biodegradability and good mechanical properties. However, the easy flammability and slow natural degradation limited its further applications, especially in high-security fields. In this work, a fully bio-based intumescent flame-retardant system was designed to reduce the fire hazard of PLA. Firstly, arginine (Arg) and phytic acid (PA) were combined through electrostatic ionic interaction, followed by the introduction of starch as a carbon source, namely APS. The UL-94 grade of PLA/APS composites reached V-0 grade by adding 3 wt% of APS and exhibited excellent anti-dripping performance. With APS addition increasing to 7 wt%, LOI value increased to 26 % and total heat release decreased from 58.4 (neat PLA) to 51.1 MJ/m2. Moreover, the addition of APS increased its crystallinity up to 83.5 % and maintained the mechanical strength of pristine PLA. Noteworthy, APS accelerated the degradation rate of PLA under submerged conditions. Compared with pristine PLA, PLA/APS showed more apparent destructive network morphology and higher mass and Mn loss, suggesting effective degradation promotion. This work provides a full biomass modification strategy to construct renewable plastic with both good flame retardancy and high degradation efficiency.

Identification of Bacterial Species Capable of Degrading LDPE

Abstract: The Plastic is polymeric material having capability of being molded or shaped by the application of heat and pressure. The low-density polyethylene(LDPE) is the type of plastic which is used in various purpose of our daily life. It is one of the major environmental problems because of its slow degradation rate .To control the pollution caused by low-density polyethylene, microbes are isolated from the dumping site of the Durg region of Chhattisgarh. These microbes are screened by the zone of clearance method for degradation of low-density polyethylene using PEG as substrate. The screened microbes were identified by morphological and biochemical characteristics.Nine bacterial isolates was selected for biodegradation studies.Confirmation of bacterial biodegradation of low-density polyethylene was performed by using weight loss measurement and pH change due to production of acidic product.One potential isolate were further identified through 16S rRNA sequences Alcaligenes faecalis was shown the high degradation rate of low-density polyethylene

Study on the Failure Process and Acoustic Emission Characteristics of Freeze–Thawed Sandstone under Cyclic Loading and Unloading

In order to investigate freeze–thawed red sandstone failure processes under cyclic loading and unloading conditions, real-time acoustic emission (AE) and scanning electron microscopy (SEM) techniques were used to reveal the fracture process of the saturated red sandstone after cyclic loading and unloading tests using uniaxial compression. The results show that the stress–strain curves of the freeze–thawed sandstones show signs of hysteresis and exhibit a two-stage evolution of “sparse → dense”. In the cyclic loading and unloading process, the modulus of elasticity in the loading process is always larger than that in the unloading process, while the Poisson’s ratio is the opposite, and the radial irreversible strain and cumulative irreversible strain are larger than those in the axial direction. As the number of freeze–thaw cycles increases, the rock specimens need more cycles of loading and unloading to make the crack volume compressive strain Δεcv+ reach the maximum value and tend to stabilize, while the crack volume extensional strain Δεcv− tends to decrease gradually. This study also shows that the growth phase of the cyclic loading and unloading process has more ringing counts and a shorter duration, while the slow degradation phase has more ringing counts with loading and less with unloading. In addition, the F-T cycle gradually changes the internal microcracks of the red sandstone from shear damage, which is dominated by shear cracks, to tensile damage, which is dominated by tensile cracks. This study’s findings contribute to our knowledge of the mechanical characteristics and sandstone’s degradation process following F-T treatment, and also serve as a guide for engineering stability analyses conducted in the presence of multiphysical field coupling.

Mechanical properties of hydrated electrospun polycaprolactone (PCL) nanofibers

Polycaprolactone (PCL) nanofibers are a promising material for biomedical applications due to their biocompatibility, slow degradation rate, and thermal stability. We electrospun PCL fibers onto a striated substrate with 12 μm wide ridges and grooves and determined their mechanical properties in an aqueous solution with a combined atomic force/inverted optical microscopy technique. Fiber diameters, D, ranged from 27 to 280 nm. The hydrated PCL fibers had an extensibility (breaking strain), εmax, of 137%. The Young's modulus, E, and tensile strength, σT, showed a strong dependence on fiber diameter, D; decreasing steeply with increasing diameter, following empirical equations E(D)=(4.3∙103∙e−D51nm+1.1∙102) MPa and σT(D)=(2.6∙103∙e−D55nm+0.6∙102) MPa. Incremental stress-strain measurements were employed to investigate the viscoelastic behavior of these fibers. The fibers exhibited stress relaxation with a fast and slow relaxation time of 3.7 ± 1.2 s and 23 ± 8 s and these experiments also allowed the determination of the elastic and viscous moduli. Cyclic stress-strain curves were used to determine that the elastic limit of the fibers, εelastic, is between 19% and 36%. These curves were also used to determine that these fibers showed small energy losses (<20%) at small strains (ε < 10%), and over 50% energy loss at large strains (ε > 50%), asymptotically approaching 61%, as Eloss=61%·(1−e−0.04*ε). Our work is the first mechanical characterization of hydrated electrospun PCL nanofibers; all previous experiments were performed on dry PCL fibers, to which we will compare our data.

Distinct Longitudinal Brain White Matter Microstructure Changes and Associated Polygenic Risk of Common Psychiatric Disorders and Alzheimer’s Disease in the UK Biobank

BackgroundDuring the course of adulthood and aging, white matter (WM) structure and organization are characterized by slow degradation processes such as demyelination and shrinkage. An acceleration of such aging processes has been linked to the development of a range of diseases. Thus, an accurate description of healthy brain maturation, particularly in terms of WM features, is fundamental to the understanding of aging. MethodsWe used longitudinal diffusion magnetic resonance imaging to provide an overview of WM changes at different spatial and temporal scales in the UK Biobank (UKB) (n = 2678; agescan 1 = 62.38 ± 7.23 years; agescan 2 = 64.81 ± 7.1 years). To examine the genetic overlap between WM structure and common clinical conditions, we tested the associations between WM structure and polygenic risk scores for the most common neurodegenerative disorder, Alzheimer’s disease, and common psychiatric disorders (unipolar and bipolar depression, anxiety, obsessive-compulsive disorder, autism, schizophrenia, attention-deficit/hyperactivity disorder) in longitudinal (n = 2329) and cross-sectional (n = 31,056) UKB validation data. ResultsOur findings indicate spatially distributed WM changes across the brain, as well as distributed associations of polygenic risk scores with WM. Importantly, brain longitudinal changes reflected genetic risk for disorder development better than the utilized cross-sectional measures, with regional differences giving more specific insights into gene-brain change associations than global averages. ConclusionsWe extend recent findings by providing a detailed overview of WM microstructure degeneration on different spatial levels, helping to understand fundamental brain aging processes. Further longitudinal research is warranted to examine aging-related gene-brain associations.

Facile and rapid fabrication of a novel 3D-printable, visible light-crosslinkable and bioactive polythiourethane for large-to-massive rotator cuff tendon repair

Facile and rapid 3D fabrication of strong, bioactive materials can address challenges that impede repair of large-to-massive rotator cuff tears including personalized grafts, limited mechanical support, and inadequate tissue regeneration. Herein, we developed a facile and rapid methodology that generates visible light-crosslinkable polythiourethane (PHT) pre-polymer resin (∼30 min at room temperature), yielding 3D-printable scaffolds with tendon-like mechanical attributes capable of delivering tenogenic bioactive factors. Ex vivo characterization confirmed successful fabrication, robust human supraspinatus tendon (SST)-like tensile properties (strength: 23 MPa, modulus: 459 MPa, at least 10,000 physiological loading cycles without failure), excellent suture retention (8.62-fold lower than acellular dermal matrix (ADM)-based clinical graft), slow degradation, and controlled release of fibroblast growth factor-2 (FGF-2) and transforming growth factor-β3 (TGF-β3). In vitro studies showed cytocompatibility and growth factor-mediated tenogenic-like differentiation of mesenchymal stem cells. In vivo studies demonstrated biocompatibility (3-week mouse subcutaneous implantation) and ability of growth factor-containing scaffolds to notably regenerate at least 1-cm of tendon with native-like biomechanical attributes as uninjured shoulder (8-week, large-to-massive 1-cm gap rabbit rotator cuff injury). This study demonstrates use of a 3D-printable, strong, and bioactive material to provide mechanical support and pro-regenerative cues for challenging injuries such as large-to-massive rotator cuff tears.