Soluble PD-L1 reprograms blood monocytes to prevent cerebral edema and facilitate recovery after ischemic stroke.

Acute cerebral ischemia triggers a profound inflammatory response. While macrophages polarized to an M2-like phenotype clear debris and facilitate tissue repair, aberrant or prolonged macrophage activation is counterproductive to recovery. The inhibitory immune checkpoint Programmed Cell Death Protein 1 (PD-1) is upregulated on macrophage precursors (monocytes) in the blood after acute cerebrovascular injury. To investigate the therapeutic potential of PD-1 activation, we immunophenotyped circulating monocytes from patients and found that PD-1 expression was upregulated in the acute period after stroke. Murine studies using a temporary middle cerebral artery (MCA) occlusion (MCAO) model showed that intraperitoneal administration of soluble Programmed Death Ligand-1 (sPD-L1) significantly decreased brain edema and improved overall survival. Mice receiving sPD-L1 also had higher performance scores short-term, and more closely resembled sham animals on assessments of long-term functional recovery. These clinical and radiographic benefits were abrogated in global and myeloid-specific PD-1 knockout animals, confirming PD-1+ monocytes as the therapeutic target of sPD-L1. Single-cell RNA sequencing revealed that treatment skewed monocyte maturation to a non-classical Ly6Clo, CD43hi, PD-L1+ phenotype. These data support peripheral activation of PD-1 on inflammatory monocytes as a therapeutic strategy to treat neuroinflammation after acute ischemic stroke.

Regulation of sensorimotor gating via Disc1/Huntingtin-mediated Bdnf transport in the cortico-striatal circuit.

Sensorimotor information processing underlies normal cognitive and behavioral traits and has classically been evaluated through prepulse inhibition (PPI) of a startle reflex. PPI is a behavioral dimension deregulated in several neurological and psychiatric disorders, yet the mechanisms underlying the cross-diagnostic nature of PPI deficits across these conditions remain to be understood. To identify circuitry mechanisms for PPI, we performed circuitry recording over the prefrontal cortex and striatum, two brain regions previously implicated in PPI, using wild-type (WT) mice compared to Disc1-locus-impairment (LI) mice, a model representing neuropsychiatric conditions. We demonstrated that the corticostriatal projection regulates neurophysiological responses during the PPI testing in WT, whereas these circuitry responses were disrupted in Disc1-LI mice. Because our biochemical analyses revealed attenuated brain-derived neurotrophic factor (Bdnf) transport along the corticostriatal circuit in Disc1-LI mice, we investigated the potential role of Bdnf in this circuitry for regulation of PPI. Virus-mediated delivery of Bdnf into the striatum rescued PPI deficits in Disc1-LI mice. Pharmacologically augmenting Bdnf transport by chronic lithium administration, partly via phosphorylation of Huntingtin (Htt) serine-421 and its integration into the motor machinery, restored striatal Bdnf levels and rescued PPI deficits in Disc1-LI mice. Furthermore, reducing the cortical Bdnf expression negated this rescuing effect of lithium, confirming the key role of Bdnf in lithium-mediated PPI rescuing. Collectively, the data suggest that striatal Bdnf supply, collaboratively regulated by Htt and Disc1 along the corticostriatal circuit, is involved in sensorimotor gating, highlighting the utility of dimensional approach in investigating pathophysiological mechanisms across neuropsychiatric disorders.

Measurement of anatomical parameters of anterior transpedicular root screw intervertebral fusion system of cervical spine.

OBJECTIVE: This study aims to investigate the feasibility of the anterior transpedicular root screw (ATPRS) intervertebral fusion system for the cervical spine and provide a basis for the design of the ATPRS intervertebral fusion system. METHODS: A total of 60 healthy adult cervical spine CT images examined from our hospital were selected, including 30 males and 30 females, with an average age of 39.6 ± 4.8 years. The image data was imported into Mimics 21.0 software in DICOM format for 3D model reconstruction. Simulated screw insertion was performed on both sides of the midline of the intervertebral space. The entry point (P1) was determined when the upper and lower screw paths did not overlap. When the screw was tangent to the medial edge of the Luschka joint, the insertion point was determined as the entry point (P2). Measurements were taken and recorded for the following parameters: distance from the screw entry point to the midline of the intervertebral space (DPM), the simulated screw length, inclination angle, cranial/caudal tilted angle, the anterior-posterior (AP) and mediolateral (ML) diameters of the cervical intervertebral space, the heights of the anterior, middle, and posterior edges of the cervical intervertebral space, and the curvature diameter of the lower end plate of the cervical vertebral body. Statistical analysis was performed on the measurement results. RESULTS: The screw entry area (P1P2) showed an increasing trend from C3-C7 in both male (2.92-6.08 mm) and female (2.32-5.12 mm) groups. There were statistical differences between men and women at the same level (P < 0.05). The average screw length of men and women was greater than 20 mm, and the upper and lower screw lengths showed an increasing trend from C3 to C7. In the area where screws could be inserted, the range of screw inclination was as follows: male group upper screw (47.73-66.76°), lower screw (48.05-65.35°); female group upper screw (49.15-65.66°) and lower screw (49.42-63.29°); The range of cranial/caudal tilted angle of the screw was as follows: male group upper screw (32.06-39.56°), lower screw (29.12-36.95°); female group upper screw (30.97-38.92°) and lower screw (27.29-37.20°). The anterior-posterior diameter and mediolateral diameter of the cervical intervertebral space showed an increasing trend from C3 to C7 in both male and female groups. The middle height (MH) of the cervical intervertebral space was greater than the anterior edge height (AH) and posterior edge height (PD), with statistical differences (P < 0.05). CONCLUSIONS: Through the study of CT images of the cervical spine, it was determined that the ATPRS intervertebral fusion system has a feasible area for screw insertion in the cervical intervertebral space.

Reversible Transformation between Isolated Skyrmions and Bimerons.

Skyrmions and bimerons are versatile topological spin textures that can be used as information bits for both classical and quantum computing. The transformation between isolated skyrmions and bimerons is an essential operation for computing architecture based on multiple different topological bits. Here we report the creation of isolated skyrmions and their subsequent transformation to bimerons by harnessing the electric current-induced Oersted field and temperature-induced perpendicular magnetic anisotropy variation. The transformation between skyrmions and bimerons is reversible, which is controlled by the current amplitude and scanning direction. Both skyrmions and bimerons can be created in the same system through the skyrmion-bimeron transformation and magnetization switching. Deformed skyrmion bubbles and chiral labyrinth domains are found as nontrivial intermediate transition states. Our results may provide a unique way for building advanced information-processing devices using different types of topological spin textures in the same system.

Nemo-like kinase reduces mutant huntingtin levels and mitigates Huntington's disease.

Nemo-like kinase (NLK), an evolutionarily conserved serine/threonine kinase, is highly expressed in the brain, but its function in the adult brain remains not well understood. In this study, we identify NLK as an interactor of huntingtin protein (HTT). We report that NLK levels are significantly decreased in HD human brain and HD models. Importantly, overexpression of NLK in the striatum attenuates brain atrophy, preserves striatal DARPP32 levels and reduces mutant HTT (mHTT) aggregation in HD mice. In contrast, genetic reduction of NLK exacerbates brain atrophy and loss of DARPP32 in HD mice. Moreover, we demonstrate that NLK lowers mHTT levels in a kinase activity-dependent manner, while having no significant effect on normal HTT protein levels in mouse striatal cells, human cells and HD mouse models. The NLK-mediated lowering of mHTT is associated with enhanced phosphorylation of mHTT. Phosphorylation defective mutation of serine at amino acid 120 (S120) abolishes the mHTT-lowering effect of NLK, suggesting that S120 phosphorylation is an important step in the NLK-mediated lowering of mHTT. A further mechanistic study suggests that NLK promotes mHTT ubiquitination and degradation via the proteasome pathway. Taken together, our results indicate a protective role of NLK in HD and reveal a new molecular target to reduce mHTT levels.

Discovery of 7-alkyloxy- [1,2,4] triazolo[1,5-a] pyrimidine derivatives as selective positive modulators of GABAA1 and GABAA4 receptors with potent antiepileptic activity.

A series of 7-alkoxy - [1,2,4] triazolo [1, 5-a] pyrimidine derivatives were designed and synthesized. Maximal electroshock (MES) and pentylenetetrazole (PTZ) tests were utilized to access their anticonvulsant activity. Most of the series of compounds exhibited significant anti-seizure effects. Further studies demonstrated that the anticonvulsant activity of these compounds mainly depended on their allosteric potentiation of GABAA receptors. Among them, compound 10c was picked for the mechanism study due to its potent activity. The compound is more sensitive to subunit configurations of synaptic α1ß2γ2 and extrasynaptic α4ß3δ GABAA receptors, but there were no effects on NMDA receptors and Nav1.2 sodium channels. Meanwhile, 10c acted on the sites of GABAA receptors distinct from commonly used anticonvulsants benzodiazepines and barbiturates. Furthermore, studies from native neurons demonstrated that compound 10c also potentiated the activity of native GABAA receptors and reduced action potential firings in cultured cortical neurons. Such structural compounds may lay a foundation for further designing novel antiepileptic molecules.

Observation of Magnetic Skyrmion Bubbles in a van der Waals Ferromagnet Fe3GeTe2.

Two-dimensional (2D) van der Waals (vdW) magnetic materials have recently been introduced as a new horizon in materials science, and they enable potential applications for next-generation spintronic devices. Here, in this communication, the observations of stable Bloch-type magnetic skyrmions in single crystals of 2D vdW Fe3GeTe2 (FGT) are reported by using in situ Lorentz transmission electron microscopy (TEM). We find the ground-state magnetic stripe domains in FGT transform into skyrmion bubbles when an external magnetic field is applied perpendicularly to the (001) thin plate with temperatures below the Curie temperature TC. Most interestingly, a hexagonal lattice of skyrmion bubbles is obtained via field-cooling manipulation with magnetic field applied along the [001] direction. Owing to their topological stability, the skyrmion bubble lattices are stable to large field-cooling tilted angles and further reproduced by utilizing the micromagnetic simulations. These observations directly demonstrate that the 2D vdW FGT possesses a rich variety of topological spin textures, being of great promise for future applications in the field of spintronics.

Small molecule modulator of protein disulfide isomerase attenuates mutant huntingtin toxicity and inhibits endoplasmic reticulum stress in a mouse model of Huntington's disease.

Huntington's disease (HD) is caused by a cytosine-adenine-guanine (CAG) trinucleotide repeat expansion in the huntingtin (HTT) gene encoding an elongated polyglutamine tract within the N-terminal of the huntingtin protein (Htt) and leads to Htt misfolding, aberrant protein aggregation, and progressive appearance of disease symptoms. Chronic activation of endoplasmic reticulum (ER) stress by mutant Htt (mHtt) results in cellular dysfunction and ultimately cell death. Protein disulfide isomerase (PDI) is a chaperone protein located in the ER. Our previous studies demonstrated that mHtt caused PDI to accumulate at mitochondria-associated ER membranes and triggered cell death, and that modulating PDI activity using small molecules protected cells again mHtt toxicity in cell and brain slice models of HD. In this study, we demonstrated that PDI is upregulated in the HD human brain, in cell and mouse models. Chronic administration of a reversible, brain penetrable small molecule PDI modulator, LOC14 (20 mg/kg/day), significantly improved motor function, attenuated brain atrophy and extended survival in the N171-82Q HD mice. Moreover, LOC14 preserved medium spiny neuronal marker dopamine- and cyclic-AMP-regulated phosphoprotein of molecular weight 32 000 (DARPP32) levels in the striatum of HD mice. Mechanistic study revealed that LOC14 suppressed mHtt-induced ER stress, indicated by repressing the abnormally upregulated ER stress proteins in HD models. These findings suggest that LOC14 is promising to be further optimized for clinical trials of HD, and modulation of signaling pathways coping with ER stress may constitute an attractive approach to reduce mHtt toxicity and identify new therapeutic targets for treatment of HD.

Creation of Single Chain of Nanoscale Skyrmion Bubbles with Record-High Temperature Stability in a Geometrically Confined Nanostripe.

Nanoscale topologically nontrivial spin textures, such as magnetic skyrmions, have been identified as promising candidates for the transport and storage of information for spintronic applications, notably magnetic racetrack memory devices. The design and realization of a single skyrmion chain at room temperature (RT) and above in the low-dimensional nanostructures are of great importance for future practical applications. Here, we report the creation of a single skyrmion bubble chain in a geometrically confined Fe3Sn2 nanostripe with a width comparable to the featured size of a skyrmion bubble. Systematic investigations on the thermal stability have revealed that the single chain of skyrmion bubbles can keep stable at temperatures varying from RT up to a record-high temperature of 630 K. This extreme stability can be ascribed to the weak temperature-dependent magnetic anisotropy and the formation of edge states at the boundaries of the nanostripes. The realization of the highly stable skyrmion bubble chain in a geometrically confined nanostructure is a very important step toward the application of skyrmion-based spintronic devices.

Early white matter abnormalities, progressive brain pathology and motor deficits in a novel knock-in mouse model of Huntington's disease.

White matter abnormalities have been reported in premanifest Huntington's disease (HD) subjects before overt striatal neuronal loss, but whether the white matter changes represent a necessary step towards further pathology and the underlying mechanism of these changes remains unknown. Here, we characterized a novel knock-in mouse model that expresses mouse HD gene homolog (Hdh) with extended CAG repeat- HdhQ250, which was derived from the selective breeding of HdhQ150 mice. HdhQ250 mice manifest an accelerated and robust phenotype compared with its parent line. HdhQ250 mice exhibit progressive motor deficits, reduction in striatal and cortical volume, accumulation of mutant huntingtin aggregation, decreased levels of DARPP32 and BDNF and altered striatal metabolites. The abnormalities detected in this mouse model are reminiscent of several aspects of human HD. In addition, disturbed myelination was evident in postnatal Day 14 HdhQ250 mouse brain, including reduced levels of myelin regulatory factor and myelin basic protein, and decreased numbers of myelinated axons in the corpus callosum. Thinner myelin sheaths, indicated by increased G-ratio of myelin, were also detected in the corpus callosum of adult HdhQ250 mice. Moreover, proliferation of oligodendrocyte precursor cells is altered by mutant huntingtin both in vitro and in vivo. Our data indicate that this model is suitable for understanding comprehensive pathogenesis of HD in white matter and gray matter as well as developing therapeutics for HD.

Resource atlases for multi-atlas brain segmentations with multiple ontology levels based on T1-weighted MRI.

Technologies for multi-atlas brain segmentation of T1-weighted MRI images have rapidly progressed in recent years, with highly promising results. This approach, however, relies on a large number of atlases with accurate and consistent structural identifications. Here, we introduce our atlas inventories (n=90), which cover ages 4-82years with unique hierarchical structural definitions (286 structures at the finest level). This multi-atlas library resource provides the flexibility to choose appropriate atlases for various studies with different age ranges and structure-definition criteria. In this paper, we describe the details of the atlas resources and demonstrate the improved accuracy achievable with a dynamic age-matching approach, in which atlases that most closely match the subject's age are dynamically selected. The advanced atlas creation strategy, together with atlas pre-selection principles, is expected to support the further development of multi-atlas image segmentation.

Small-molecule TrkB receptor agonists improve motor function and extend survival in a mouse model of Huntington's disease.

Huntington's disease (HD) is a fatal neurodegenerative disease characterized by abnormal motor coordination, cognitive decline and psychiatric disorders. This disease is caused by an expanded CAG trinucleotide repeat in the gene encoding the protein huntingtin. Reduced levels of brain-derived neurotrophic factor (BDNF) in the brain, which results from transcriptional inhibition and axonal transport deficits mediated by mutant huntingtin, have been suggested as critical factors underlying selective neurodegeneration in both HD patients and HD mouse models. BDNF activates its high-affinity receptor TrkB and promotes neuronal survival; restoring BDNF signaling is thus of particular therapeutic interest. In the present study, we evaluated the ability of a small-molecule TrkB agonist 7,8-dihydroxyflavone (7,8-DHF) and its synthetic derivative 4'-dimethylamino-7,8- dihydroxyflavone (4'-DMA-7,8-DHF) to protect neurons in the well-characterized N171-82Q HD mouse model. We found that chronic administration of 7, 8-DHF (5 mg/kg) or 4'-DMA-7,8-DHF (1 mg/kg) significantly improved motor deficits, ameliorated brain atrophy and extended survival in these N171-82Q HD mice. Moreover, 4'-DMA-7,8-DHF preserved DARPP32 levels in the striatum and rescued mutant huntingtin-induced impairment of neurogenesis in the N171-82Q HD mice. These data highlight consideration of TrkB as a therapeutic target in HD and suggest that small-molecule TrkB agonists that penetrate the brain have high potential to be further tested in clinical trials of HD.

Toxic role of prostaglandin E2 receptor EP1 after intracerebral hemorrhage in mice.

Inflammatory mechanisms mediated by prostaglandins may contribute to the progression of intracerebral hemorrhage (ICH)-induced brain injury, but they are not fully understood. In this study, we examined the effect of prostaglandin E2 receptor EP1 (EP1R) activation and inhibition on brain injury in mouse models of ICH and investigated the underlying mechanism of action. ICH was induced by injecting collagenase, autologous blood, or thrombin into the striatum of middle-aged male and female mice and aged male mice. Effects of selective EP1R agonist ONO-DI-004, antagonist SC51089, and nonspecific Src family kinase inhibitor PP2 were evaluated by a combination of histologic, magnetic resonance imaging (MRI), immunofluorescence, molecular, cellular, and behavioral assessments. EP1R was expressed primarily in neurons and axons but not in astrocytes or microglia after ICH induced by collagenase. In middle-aged male mice subjected to collagenase-induced ICH, EP1R inhibition mitigated brain injury, brain edema, cell death, neuronal degeneration, neuroinflammation, and neurobehavioral deficits, whereas its activation exacerbated these outcomes. EP1R inhibition also was protective in middle-aged female mice and aged male mice after collagenase-induced ICH and in middle-aged male mice after blood- or thrombin-induced ICH. EP1R inhibition also reduced oxidative stress, white matter injury, and brain atrophy and improved functional outcomes. Histologic results were confirmed by MRI. Src kinase phosphorylation and matrix metalloproteinase-9 activity were increased by EP1R activation and decreased by EP1R inhibition. EP1R regulated matrix metalloproteinase-9 activity through Src kinase signaling, which mediated EP1R toxicity after collagenase-induced ICH. We conclude that prostaglandin E2 EP1R activation plays a toxic role after ICH through mechanisms that involve the Src kinases and the matrix metalloproteinase-9 signaling pathway. EP1R inhibition could be a novel therapeutic strategy to improve outcomes after ICH.

Polyglutamine amyloid core boundaries and flanking domain dynamics in huntingtin fragment fibrils determined by solid-state nuclear magnetic resonance.

In Huntington's disease, expansion of a polyglutamine (polyQ) domain in the huntingtin (htt) protein leads to misfolding and aggregation. There is much interest in the molecular features that distinguish monomeric, oligomeric, and fibrillar species that populate the aggregation pathway and likely differ in cytotoxicity. The mechanism and rate of aggregation are greatly affected by the domains flanking the polyQ segment within exon 1 of htt. A "protective" C-terminal proline-rich flanking domain inhibits aggregation by inducing polyproline II structure (PPII) within an extended portion of polyQ. The N-terminal flanking segment (htt(NT)) adopts an α-helical structure as it drives aggregation, helps stabilize oligomers and fibrils, and is seemingly integral to their supramolecular assembly. Via solid-state nuclear magnetic resonance (ssNMR), we probe how, in the mature fibrils, the htt flanking domains impact the polyQ domain and in particular the localization of the ß-structured amyloid core. Using residue-specific and uniformly labeled samples, we find that the amyloid core occupies most of the polyQ domain but ends just prior to the prolines. We probe the structural and dynamical features of the remarkably abrupt ß-sheet to PPII transition and discuss the potential connections to certain htt-binding proteins. We also examine the htt(NT) α-helix outside the polyQ amyloid core. Despite its presumed structural and demonstrated stabilizing roles in the fibrils, quantitative ssNMR measurements of residue-specific dynamics show that it undergoes distinct solvent-coupled motion. This dynamical feature seems reminiscent of molten-globule-like α-helix-rich features attributed to the nonfibrillar oligomeric species of various amyloidogenic proteins.

Enhancing recall in automated record screening: A resampling algorithm.

Literature screening is the process of identifying all relevant records from a pool of candidate paper records in systematic review, meta-analysis, and other research synthesis tasks. This process is time consuming, expensive, and prone to human error. Screening prioritization methods attempt to help reviewers identify most relevant records while only screening a proportion of candidate records with high priority. In previous studies, screening prioritization is often referred to as automatic literature screening or automatic literature identification. Numerous screening prioritization methods have been proposed in recent years. However, there is a lack of screening prioritization methods with reliable performance. Our objective is to develop a screening prioritization algorithm with reliable performance for practical use, for example, an algorithm that guarantees an 80% chance of identifying at least 80 % of the relevant records. Based on a target-based method proposed in Cormack and Grossman, we propose a screening prioritization algorithm using sampling with replacement. The algorithm is a wrapper algorithm that can work with any current screening prioritization algorithm to guarantee the performance. We prove, with mathematics and probability theory, that the algorithm guarantees the performance. We also run numeric experiments to test the performance of our algorithm when applied in practice. The numeric experiment results show this algorithm achieve reliable performance under different circumstances. The proposed screening prioritization algorithm can be reliably used in real world research synthesis tasks.

Recent development and future application of biodegradable ureteral stents.

Ureteral stenting is a common clinical procedure for the treatment of upper urinary tract disorders, including conditions such as urinary tract infections, tumors, stones, and inflammation. Maintaining normal renal function by preventing and treating ureteral obstruction is the primary goal of this procedure. However, the use of ureteral stents is associated with adverse effects, including surface crusting, bacterial adhesion, and lower urinary tract symptoms (LUTS) after implantation. Recognizing the need to reduce the complications associated with permanent ureteral stent placement, there is a growing interest among both physicians and patients in the use of biodegradable ureteral stents (BUS). The evolution of stent materials and the exploration of different stent coatings have given these devices different roles tailored to different clinical needs, including anticolithic, antibacterial, antitumor, antinociceptive, and others. This review examines recent advances in BUS within the last 5 years, providing an in-depth analysis of their characteristics and performance. In addition, we present prospective insights into the future applications of BUS in clinical settings.

Recent advances in drug delivery systems based on natural and synthetic polymes for treating obesity.

Obesity stands as a pervasive global public health issue, posing a formidable threat to human well-being as its prevalence continues to surge year by year. Presently, pharmacological treatment remains the favored adjunct strategy for addressing obesity. However, conventional delivery methods suffer from low bioavailability and the potential for side effects, underscoring the pressing need for more efficient and targeted delivery approaches. Recent research has delved extensively into emerging drug delivery systems employing polymers as carriers, with numerous preclinical studies contributing to the growing body of knowledge. This review concentrates on the utilization of natural polymers as drug delivery systems for the treatment of obesity, encompassing recent advancements in both natural and synthetic polymers. The comprehensive exploration includes an analysis of the advantages and disadvantages associated with these polymer carriers. The examination of these characteristics provides valuable insights into potential future developments in the field of drug delivery for obesity treatment.

[Feasibility of a novel type of complex anterior cervical fixation by using Mimics software].

OBJECTIVE: To investigate the feasibility of mimics software in analyzing a new type of complex anterior cervical fixation -- anterior transpedicular screw fixation+zero notch internal fixation. METHODS: From January 2021 to September 2022, 50 normal pedestrians who underwent cervical spine CT scanning were selected for C1-C7 segment scanning, including 27 males and 23 females, aged from 25 to 65 years old with an average of (46.0 ± 9.0) years old. The dicom format is exported and engraved into the CD, and use the mimics software to perform 3D reconstruction of each segment. A simulated screw is placed on the image according to the critical value of zero notch screw (head and tail angle 44°, internal angle 29°). The position of zero notch screw in each segment is observed to determine the feasibility of anterior transpedicular screw fixation plus zero notch internal fixation. RESULTS: For the upper zero notch screws the three-dimensional images of the cervical spine across all 50 subjects within the C3-C7 segments demonstrated safe position, with no instances of intersection with ATPS. For the lower zero notch screw, in C3-C4 and C4-C5, 4 out of 50 subjects are in the safe position in the three-dimensional images of cervical vertebrae, and 46 cases could achieve secure screw placement when the maximum caudal angle is(32.3±1.9) ° and (36.1±2.2) °, respectively. In C5-C6 and C6-C7 segments, no lower zero notch screws intersected with ATPS, and all screws are in safe positions. CONCLUSION: Lower cervical anterior pedicle screw fixation plus zero notch internal fixation can achieve successful nail placement through the selected entry point and position.

Advances focusing on the application of decellularization methods in tendon-bone healing.

BACKGROUND: The tendon or ligament is attached to the bone by a triphasic but continuous area of heterogeneous tissue called the tendon-bone interface (TBI). The rapid and functional regeneration of TBI is challenging owing to its complex composition and difficulty in self-healing. The development of new technologies, such as decellularization, has shown promise in the regeneration of TBI. Several ex vivo and in vivo studies have shown that decellularized grafts and decellularized biomaterial scaffolds achieved better efficacy in enhancing TBI healing. However further information on the type of review that is available is needed. AIM OF THE REVIEW: In this review, we discuss the current application of decellularization biomaterials in promoting TBI healing and the possible mechanisms involved. With this work, we would like to reveal how tissues or biomaterials that have been decellularized can improve tendon-bone healing and to provide a theoretical basis for future related studies. KEY SCIENTIFIC CONCEPTS OF THE REVIEW: Decellularization is an emerging technology that utilizes various chemical, enzymatic and/or physical strategies to remove cellular components from tissues while retaining the structure and composition of the extracellular matrix (ECM). After decellularization, the cellular components of the tissue that cause an immune response are removed, while various biologically active biofactors are retained. This review further explores how tissues or biomaterials that have been decellularized improve TBI healing.

Animal models of tendon calcification: Past, present, and future.

Tendon calcification is a common clinical condition that frequently occurs as a complication after tendon injury and surgery, or as an expression of fibrodysplasia ossificans progressiva. This condition can be referred to by various names in clinical practice and literature, including tendon ossification, tendon mineralization, heterotopic ossification, and calcific tendonitis. The exact pathogenesis of tendon calcification remains uncertain, but current mainstream research suggests that calcification is mostly cell mediated. To further elucidate the pathogenesis of tendon calcification and to better simulate the overall process, selecting appropriate experimental animal models is important. Numerous animal models have been utilized in various clinical studies, each with its own set of advantages and limitations. In this review, we have discussed the advancements made in research on animal models of tendon calcification, with a focus on the selection of experimental animals, the sites of injury in these models, and the methods employed for modeling.