SCAN: sequence-based context-aware association network for hepatic vessel segmentation.

Accurate segmentation of hepatic vessel is significant for the surgeons to design the preoperative planning of liver surgery. In this paper, a sequence-based context-aware association network (SCAN) is designed for hepatic vessel segmentation, in which three schemes are incorporated to simultaneously extract the 2D features of hepatic vessels and capture the correlations between adjacent CT slices. The two schemes of slice-level attention module and graph association module are designed to bridge feature gaps between the encoder and the decoder in the low- and high-dimensional spaces. The region-edge constrained loss is designed to well optimize the proposed SCAN, which integrates cross-entropy loss, dice loss, and edge-constrained loss. Experimental results indicate that the proposed SCAN is superior to several existing deep learning frameworks, in terms of 0.845 DSC, 0.856 precision, 0.866 sensitivity, and 0.861 F1-score.

Clinical usage of dental stem cells and their derived extracellular vesicles.

Stem cell-based therapies remain at the forefront of tissue engineering and regenerative medicine because stem cells are a unique cell source with enormous potential to treat incurable diseases and even extend lifespans. The search for the best stem cell candidates continues to evolve and in recent years, dental stem cells have received significant attention due to their easy accessibility, high plasticity, and multipotential properties. Dental stem cells have been the subject of extensive research in both animal models and human clinical trials over the past two decades, and have demonstrated significant potential in ocular therapy, bone tissue engineering, and, of course, therapeutic applications in dentistry such as regenerative endodontics and periodontal tissue regeneration. These new sources of cells may be advantageous for cellular therapy and the advancement of regenerative medicine strategies, such as allogeneic transplantation or therapy with extracellular vesicles (EVs), which are functional nanoscale membrane vesicles produced by cells. This chapter discusses the accumulating research findings on cell-based regenerative therapy utilizing dental stem cells and their derived EVs, which could be a viable tool for the treatment of a variety of diseases and hence extremely valuable to mankind in the long run.

Engineered adult stem cells: Current clinical trials status of disease treatment.

Regenerative medicine is an interdisciplinary field involving the process of replacing and regenerating cells/tissues or organs by integrating medicine, science, and engineering principles to enhance the intrinsic regenerative capacity of the host. Recently, engineered adult stem cells have gained attention for their potential use in regenerative medicine by reducing inflammation and modulating the immune system. This chapter introduces adult stem cell engineering and chimeric antigen receptor T cells (CAR T) gene therapy and summarises current engineered stem cell- and extracellular vesicles (EVs)-focused clinical trial studies that provide the basis for the proposal of a personalised medicine approach to diseases diagnosis and treatment.

A High-Precision Multi-Beam Optical Measurement Method for Cylindrical Surface Profile.

To automatically measure the surface profile of a cylindrical workpiece, a high-precision multi-beam optical method is proposed in this paper. First, some successive images for the cylindrical workpiece's surface are acquired by a multi-beam angle sensor under different light directions. Then, the light directions are estimated based on the feature regions in the images to calculate surface normal vectors. Finally, according to the relationship of the surface normal vector and the vertical section of the workpiece's surface, a depth map is reconstructed to achieve the curvature surface, which can be employed to measure the curvature radius of the cylindrical workpiece's surface. Experimental results indicate that the proposed measurement method can achieve good measurement precision with a mean error of the curvature radius of a workpiece's surface of 0.89% at a reasonable speed of 10.226 s, which is superior to some existing methods.

Plasma-activated medium triggers immunomodulation and autophagic activity for periodontal regeneration.

Periodontitis is an infection-induced inflammation, evidenced by an increase in inflammatory macrophage infiltration. Recent research has highlighted the role of plasma-activated medium (PAM) as a regulator of the innate immune system, where macrophages are the main effector cells. This study therefore aims to investigate the immunomodulatory effects of PAM on macrophages and its potential applications for periodontitis management. PAM was generated using an argon jet and applied to culture macrophages. Proinflammatory macrophage markers were significantly reduced after PAM stimulation, and this was correlated with the activation of autophagy via the Akt signaling pathway. Further investigations on the proregenerative effects of PAM-treated macrophages on periodontal ligament cells (PDLCs) revealed a significant increase in the expression of osteogeneis/cementogenesis-associated markers as well as mineralization nodule formation. Our findings suggest that PAM is an excellent candidate for periodontal therapeutic applications.

Goniothalamin prevents lipopolysaccharide-induced acute lung injury and inflammation via TLR-4/NF-κB signaling pathway.

Goniothalamin (GTN) is a natural compound isolated from Goniothalamus species. It is a potent anti-inflammatory agent. However, there is a paucity of scientific data about its toxicity. This study investigated GTN's anti-inflammatory mechanism and lipopolysaccharide (LPS)-induced lung injury in mice. Mice were distributed into four groups and injected with GTN intraperitoneally (Dosage-50 and 100 mg/kg). We analyzed the wet/dry weight ratio, infiltrated inflammatory cell count, myeloperoxidase (MPO) activity, and histopathological changes in the lung tissues of the mice. Results revealed GTN alleviated LPS-induced inflammation in mice. Western Blot and enzyme-linked immunosorbent assay techniques were used to investigate the effect of GTN on pro-inflammatory cytokines and proteins involved in the MAPK and nuclear factor-B (NF-κB) signaling pathways. Cytokines (macrophage migration inhibitory factor, interleukin [IL]-13, IL-6, TNF-α, and IL-1ß) were inhibited by GTN. However, IL-10 was upregulated. Western blot analysis indicated that GTN suppressed the phosphorylation of jun N-terminal kinase, nuclear factor NF-kappa-B p65, I-kappa-B, extracellular signal-regulated kinases, NF-κB, and p38. GTN also suppressed the expression of TLR-4 protein, thereby, inhibiting MAPK and NF-κB signaling pathways. Thus, GTN can effectively prevent and cure acute lung injury.

Is Toxoplasma gondii infection a concern in individuals with rheumatic diseases? Evidence from a case-control study based on serological diagnosis.

Toxoplasma gondii infection in clinical cases of rheumatic diseases is increasing, whereas, the relationship between T. gondii infection and rheumatic diseases is still ambiguous and contradictory. Thus, the present case-control study based on serological diagnosis was carried out to identify the underlying relationship between T. gondii infection and rheumatic diseases in China. Serological results showed that rheumatic patients (17.25%, 79/458) had a significantly higher T. gondii seroprevalence than control subjects (10.70%, 49/458) (p = 0.004). However, the difference in T. gondii seroprevalence among clinical rheumatic disease forms was insignificant. Moreover, disease duration not effect the T. gondii seroprevalence in the included clinical rheumatic patients. Three risk factors (presence of cats at home, blood transfusion history, and consumption of raw shellfish) were identified through multivariate analysis to affect the T. gondii seroprevalence in the included clinical rheumatic patients. In conclusion, these results indicate that the latent T. gondii infection in clinical rheumatic patients should cause alarm and attention in the course of future scientific research or clinical treatment.

Metal-organic framework glass composites.

The melting phenomenon in metal-organic frameworks (MOFs) has been recognised as one of the fourth generation MOF paradigm behaviours. Molten MOFs have high processibility for producing mechanically robust glassy MOF macrostructures, and they also offer highly tunable interfacial characteristics when combined with other types of functional materials, such as crystalline MOFs, inorganic glass and metal halide perovskites. As a result, MOF glass composites have emerged as a family of functional materials with dynamic properties and hierarchical structural control. These nanocomposites allow for sophisticated materials science studies as well as the fabrication of next-generation separation, catalysis, optical, and biomedical devices. Here, we review the approaches for designing, fabricating, and characterising MOF glass composites. We determine the key application opportunities enabled by these composites and explore the remaining hurdles, such as improving thermal and chemical compatibility, regulating interfacial properties, and scalability.

TNF-α and OSX mRNA of Salivary Small Extracellular Vesicles in Periodontitis: A Pilot Study.

This cross-sectional pilot study explored extracellular vesicle (EV)-derived gene expression of markers for bone turnover and pro-inflammatory cytokines in periodontal disease. Whole unstimulated saliva was collected from 52 participants (18 healthy, 13 gingivitis, and 21 stages III/IV periodontitis), from which salivary small extracellular vesicles (sEVs) were enriched using the size-exclusion chromatography method, and characterized by morphology, EV-protein, and size distribution, using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), and Nanoparticle Tracking Analysis (NTA), respectively. Bone turnover markers and pro-inflammatory cytokines in salivary sEVs were evaluated using reverse transcription PCR. Salivary sEVs morphology, mode, size distribution, and particle concentration were comparable between healthy, gingivitis, and periodontitis patients. The CD9+ subpopulation was significantly higher in periodontitis-derived salivary sEVs compared with healthy. The detection of sEVs mRNA for osterix and tumor necrosis factor-alpha was significantly decreased and increased, respectively, in periodontitis compared with healthy controls, with good discriminatory power for periodontitis diagnosis (area under the curve >0.72). This pilot study demonstrated that salivary sEVs mRNAs may serve as a potential noninvasive biomarker source for periodontitis diagnosis.

An Optimized Method for Microcomputed Tomography Analysis of Trabecular Parameters of Metal Scaffolds for Bone Ingrowth.

Owing to its superior mechanical and biological properties, titanium metal is widely used in dental implants, orthopedic devices, and bone regenerative materials. Advances in 3D printing technology have led to more and more metal-based scaffolds being used in orthopedic applications. Microcomputed tomography (µCT) is commonly applied to evaluate the newly formed bone tissues and scaffold integration in animal studies. However, the presence of metal artifacts dramatically hinders the accuracy of µCT analysis of new bone formation. To acquire reliable and accurate µCT results that reflect new bone formation in vivo, it is crucial to lessen the impact of metal artifacts. Herein, an optimized procedure for calibrating µCT parameters using histological data was developed. In this study, the porous titanium scaffolds were fabricated by powder bed fusion based on computer-aided design. These scaffolds were implanted in femur defects created in New Zealand rabbits. After 8 weeks, tissue samples were collected to assess new bone formation using µCT analysis. Resin-embedded tissue sections were then used for further histological analysis. A series of deartifact two-dimensional (2D) µCT images were obtained by setting the erosion radius and the dilation radius in the µCT analysis software (CTan) separately. To get the µCT results closer to the real value, the 2D µCT images and corresponding parameters were subsequently selected by matching the histological images in the particular region. After applying the optimized parameters, more accurate 3D images and more realistic statistical data were obtained. The results demonstrate that the newly established method of adjusting µCT parameters can effectively reduce the influence of metal artifacts on data analysis to some extent. For further validation, other metal materials should be analyzed using the process established in this study.

Immunomodulatory nanotherapeutic approaches for periodontal tissue regeneration.

Periodontitis is an infection-induced inflammatory disease characterized by progressive destruction of tooth supporting tissues, which, if left untreated, can result in tooth loss. The destruction of periodontal tissues is primarily caused by an imbalance between the host immune protection and immune destruction mechanisms. The ultimate goal of periodontal therapy is to eliminate inflammation and promote the repair and regeneration of both hard and soft tissues, so as to restore the physiological structure and function of periodontium. Advancement in nanotechnologies has enabled the development of nanomaterials with immunomodulatory properties for regenerative dentistry. This review discusses the immune mechanisms of the major effector cells in the innate and adaptive immune systems, the physicochemical and biological properties of nanomaterials, and the research advancements in immunomodulatory nanotherapeutic approaches for the management of periodontitis and the regeneration of periodontal tissues. The current challenges, and prospects for future applications of nanomaterials are then discussed so that researchers at the intersections of osteoimmunology, regenerative dentistry and materiobiology will continue to advance the development of nanomaterials for improved periodontal tissue regeneration.

Association between periodontitis and uric acid levels in blood and oral fluids: a systematic review and meta-analysis.

BACKGROUND: Uric acid, a formerly-known antioxidant that has recently been linked to numerous inflammatory diseases as a pro-inflammatory and -oxidative mediator in pathological conditions. It is imperative to reassess the association between periodontitis and uric acid locally and systematically. The aim of this systematic review was to systemically evaluate the association between periodontitis and the uric acid (UA) levels in blood, saliva and gingival crevicular fluid (GCF). METHODS: Relevant clinical studies up to January 28, 2023 were identified and retrieved from electronic databases including PubMed, Scopus, EMBASE and Web of Science, with periodontitis, uric acid, hyperuricemia and gout as the keywords. The weighted (WMD) or standardized mean difference (SMD) was calculated using fixed- or random-effect models. Methodological heterogeneity was assessed. RESULTS: Sixteen eligible observational studies and one RCT were enrolled, which included 1354 patients with periodontitis and 989 controls. Three sample types for UA detection were involved, including blood (n = 8), saliva (n = 9) and GCF (n = 1). Meta-analysis demonstrated an enhanced plasma UA concentration (WMD = 1.00 mg/dL, 95% CI 0.63 to 1.37, P < 0.001) but a decreased salivary UA level (SMD = -0.95, 95% CI -1.23 to -0.68, P < 0.001) in periodontitis versus control. Statistical heterogeneity among the plasma- and saliva-tested studies were moderate (I2 = 58.3%, P = 0.066) and low (I2 = 33.8%, P = 0.196), respectively. CONCLUSIONS: Within the limitations of the enrolled studies, it seems that there is an association between periodontitis and increased blood UA and decreased salivary UA. (Registration no. CRD42020172535 in Prospero).

Osteoimmunomodulatory Nanoparticles for Bone Regeneration.

Treatment of large bone fractures remains a challenge for orthopedists. Bone regeneration is a complex process that includes skeletal cells such as osteoblasts, osteoclasts, and immune cells to regulate bone formation and resorption. Osteoimmunology, studying this complicated process, has recently been used to develop biomaterials for advanced bone regeneration. Ideally, a biomaterial shall enable a timely switch from early stage inflammatory (to recruit osteogenic progenitor cells) to later-stage anti-inflammatory (to promote differentiation and terminal osteogenic mineralization and model the microstructure of bone tissue) in immune cells, especially the M1-to-M2 phenotype switch in macrophage populations, for bone regeneration. Nanoparticle (NP)-based advanced drug delivery systems can enable the controlled release of therapeutic reagents and the delivery of therapeutics into specific cell types, thereby benefiting bone regeneration through osteoimmunomodulation. In this review, we briefly describe the significance of osteoimmunology in bone regeneration, the advancement of NP-based approaches for bone regeneration, and the application of NPs in macrophage-targeting drug delivery for advanced osteoimmunomodulation.

Osteo-Immunomodulatory Role of Interleukin-4-Immobilized Plasma Immersion Ion Implantation Membranes for Bone Regeneration.

Barrier membranes for guided tissue regeneration are essential for bone repair and regeneration. The implanted membranes may trigger early inflammatory responses as a foreign material, which can affect the recruitment and differentiation of bone cells during tissue regeneration. The purpose of this study was to determine whether immobilizing interleukin 4 (IL4) on plasma immersion ion implantation (PIII)-activated surfaces may alter the osteo-immunoregulatory characteristics of the membranes and produce pro-osteogenic effects. In order to immobilize IL4, polycaprolactone surfaces were modified using the PIII technology. No discernible alterations were found between the morphology before and after PIII treatment or IL4 immobilization. IL4-immobilized PIII surfaces polarized macrophages to an M2 phenotype and mitigated inflammatory cytokine production under lipopolysaccharide stimulation. Interestingly, the co-culture of macrophages (on IL4-immobilized PIII surfaces) and bone marrow-derived mesenchymal stromal cells enhanced the production of angiogenic and osteogenic factors and triggered autophagy activation. Exosomes produced by PIII + IL4-stimulated macrophages were also found to play a role in osteoblast differentiation. In conclusion, the osteo-immunoregulatory properties of bone materials can be modified by PIII-assisted IL4 immobilization, creating a favorable osteoimmune milieu for bone regeneration.

Micro/nano-modified titanium surfaces accelerate osseointegration via Rab7-dependent mitophagy.

To achieve rapid and successful osseointegration of titanium (Ti) implants, the underlying mechanisms of surface modification-mediated bone metabolism need to be clarified. Given that the microenvironment surrounding Ti implants may be altered after implant insertion, mitophagy as a key control system for cellular homeostasis is most likely to regulate osseointegration. Recent findings suggest that PTEN-induced putative kinase 1 (Pink1)/Parkin-mediated mitophagy plays a key role in bone metabolism. Since the micro/nano-modified surfaces of Ti implants have been widely appreciated for osseointegration acceleration, we used two common micro/nano-modified techniques and demonstrated elevations of both the osteo-differentiation potential and Pink1/Parkin pathway of osteoblasts. Moreover, the Pink1/Parkin pathway exhibited an upward trend during osteoblast differentiation. However, when osteoblasts were treated with CCCP, a Pink1/Parkin inducer, the osteo-differentiation potential decreased. Our further study showed that the small GTPase Rab7, which was inhibited by CCCP, was essential for the Pink1/Parkin pathway. Upon Pink1 or Rab7 knockdown, the pro-osteogenic effect of micro/nano-modified Ti surfaces was significantly weakened. The present results demonstrated that Rab7 activation was essential for active mitophagy and osteogenesis. In addition, Rab7 was confirmed to mediate the process of autophagosome formation. Our findings provide novel insights into new targets for osseointegration promotion, regardless of Ti surface characteristics.

Bioceramic micro-fillers reinforce antibiofilm and remineralization properties of clear aligner attachment materials.

Introduction: Clear aligners, while offering a more hygienic alternative to fixed appliances, are still associated with challenges including plaque accumulation and enamel demineralization. The aim of the present study was to investigate the antibiofilm and remineralization effectiveness of innovative flowable composite attachments containing bioceramic micro-fillers. Methods: Four experimental attachments were formulated and bonded to human enamel specimens: 3M Filtek Supreme flowable composite (Filtek SF) + 10% bioactive glass 45S5 (BAG), Filtek SF + 30% BAG, Filtek SF + 10% Bredigite (BRT), Filtek SF + 30% BRT. Plaque biofilms were grown on the bonded enamel using a standardized protocol and the biofilm-killing effect was assessed by confocal laser scanning microscopy and scanning electron microscopy. Vickers microhardness was measured to evaluate the remineralization effect of the attachments containing bioceramic fillers after acid challenge. Shear bond test was performed to assess the bonding strength. Results: Attachments with bioceramic fillers significantly inhibited plaque biofilm growth in 3 weeks on enamel, contributing over 20% bacterial cell killing in 10% filler groups and over 30% killing in 30% filler groups. All four experimental groups demonstrated significantly higher microhardness values than the control group without fillers on the attachment side. The shear bonding strength was not compromised in the attachments with micro-fillers. Discussion: Proper incorporation of bioceramic micro-fillers in attachments provides an innovative approach for clear aligner therapy with reinforced antibiofilm and remineralization effects without weakening shear bonding strength.

Current Advances in 3D Dynamic Cell Culture Systems.

The traditional two-dimensional (2D) cell culture methods have a long history of mimicking in vivo cell growth. However, these methods cannot fully represent physiological conditions, which lack two major indexes of the in vivo environment; one is a three-dimensional 3D cell environment, and the other is mechanical stimulation; therefore, they are incapable of replicating the essential cellular communications between cell to cell, cell to the extracellular matrix, and cellular responses to dynamic mechanical stimulation in a physiological condition of body movement and blood flow. To solve these problems and challenges, 3D cell carriers have been gradually developed to provide a 3D matrix-like structure for cell attachment, proliferation, differentiation, and communication in static and dynamic culture conditions. 3D cell carriers in dynamic culture systems could primarily provide different mechanical stimulations which further mimic the real in vivo microenvironment. In this review, the current advances in 3D dynamic cell culture approaches have been introduced, with their advantages and disadvantages being discussed in comparison to traditional 2D cell culture in static conditions.

Characteristic analysis of clinical trials for new traditional Chinese medicines in mainland China from 2013 to 2021.

Objective: Based on the clinical trials registered on the platform for the registry and publicity of clinical drug trials of the National Medical Products Administration (NMPA), the registration and approval of clinical trials of traditional Chinese medicines (TCMs) in mainland China from 2013 to 2021 were reviewed. Methods: Clinical trials of new TCMs published in Chinese were retrieved from the platform for the registry and publicity of clinical drug trials. The number of registered trials and approved trials, status of clinical trials, therapeutic area of clinical trials for the treatment of diseases, type of trial design, sample size, sponsors, and leading clinical trial centers were evaluated. Results: From 2013 to 2021, a total of 965 clinical trials of new drugs applied in TCM were registered on the aforementioned NMPA platform, comprising 117 phase I trials, 586 phase II trials, 174 phase III trials, 40 phase IV trials, and 48 other clinical trials. The treatment fields included the respiratory system, alimentary tract and metabolism, genetic system and reproductive hormones, and cardiovascular system. Among the 760 phase II and phase III trials, 98.9% were randomized, 95.4% were double-blind, and 98.2% were parallel controlled trials, and the proportion of placebo-controlled trials increased year by year from 2013 to 2021. From 2013 to 2021, 123 new TCMs were approved in mainland China. Conclusion: From 2015 to 2021, the number of registered clinical trials of new TCMs remained low. The approval rate was also low, but the clinical trial design was greatly improved.

Phase control of ZIF-7 nanoparticles via mechanochemical synthesis.

Mechanochemical synthesis is a greener synthesis route to form functional metal organic frameworks (MOFs) compared to the typical solvothermal method. Here we demonstrate the crystal phase control of a widely functional zeolitic imidazolate framework, ZIF-7, and its variations via the mechanochemical synthesis route.