Kirigami-enabled stretchable laser-induced graphene heaters for wearable thermotherapy.

Flexible and stretchable heaters are increasingly recognized for their great potential in wearable thermotherapy to treat muscle spasms, joint injuries and arthritis. However, issues like lengthy processing, high fabrication cost, and toxic chemical involvement are obstacles on the way to popularize stretchable heaters for medical use. Herein, using a single-step customizable laser fabrication method, we put forward the design of cost-effective wearable laser-induced graphene (LIG) heaters with kirigami patterns, which offer multimodal stretchability and conformal fit to the skin around the human body. First, we develop the manufacturing process of the LIG heaters with three different kirigami patterns enabling reliable stretchability by out-of-plane buckling. Then, by adjusting the laser parameters, we confirm that the LIG produced by medium laser power could maintain a balance between mechanical strength and electrical conductivity. By optimizing cutting-spacing ratios through experimental measurements of stress, resistance and temperature profiles, as well as finite element analysis (FEA), we determine that a larger cutting-spacing ratio within the machining precision will lead to better mechanical, electrical and heating performance. The optimized stretchable heater in this paper could bear significant unidirectional strain over 100% or multidirectional strain over 20% without major loss in conductivity and heating performance. On-body tests and fatigue tests also proved great robustness in practical scenarios. With the advantage of safe usage, simple and customizable fabrication, easy bonding with skin, and multidirectional stretchability, the on-skin heaters are promising to substitute the traditional heating packs/wraps for thermotherapy.

Multileaf Collimator Modeling and Commissioning for Complex Radiation Treatment Plans Using 2-Dimensional (2D) Diode Array MapCHECK2.

Purpose: This study aims to develop a data-collecting package ExpressMLC and investigate the applicability of MapCHECK2 for multileaf collimator (MLC) modeling and commissioning for complex radiation treatment plans. Materials and methods: The MLC model incorporates realistic parameters to account for sophisticated MLC features. A set of 8 single-beam plans, denoted by ExpressMLC, is created for the determination of parameters. For the commissioning of the MLC model, 4 intensity modulated radiation therapy (IMRT) plans specified by the AAPM TG 119 report were transferred to a computed tomography study of MapCHECK2, recalculated, and compared to measurements on a Varian accelerator. Both per-beam and composite-beam dose verification were conducted. Results: Through sufficient characterization of the MLC model, under 3%/2 mm and 2%/2 mm criteria, MapCHECK2 can be used to accurately verify per beam dose with gamma passing rate better than 90.9% and 89.3%, respectively, while the Gafchromic EBT3 films can achieve gamma passing rate better than 89.3% and 85.7%, respectively. Under the same criteria, MapCHECK2 can achieve composite beam dose verification with a gamma passing rate better than 95.9% and 90.3%, while the Gafchromic EBT3 films can achieve a gamma passing rate better than 96.1% and 91.8%; the p-value from the Mann Whitney test between gamma passing rates of the per beam dose verification using full MapCHECK2 package calibrated MLC model and film calibrated MLC model is .44 and .47, respectively; the p-value between those of the true composite beam dose verification is .62 and .36, respectively. Conclusion: It is confirmed that the 2-dimensional (2D) diode array MapCHECK2 can be used for data collection for MLC modeling with the combination of the ExpressMLC package of plans, whose doses are sufficient for the determination of MLC parameters. It could be a fitting alternative to films to boost the efficiency of MLC modeling and commissioning without sacrificing accuracy.

High-Level Production of scFv-Fc Antibody Using an Artificial Promoter System with Transcriptional Positive Feedback Loop of Transactivator in CHO Cells.

With the increasing demand for therapeutic antibodies, CHO cells have become the de facto standard as producer host cells for biopharmaceutical production. High production yields are required for antibody production, and developing a high-titer production system is increasingly crucial. This study was established to develop a high-production system using a synthetic biology approach by designing a gene expression system based on an artificial transcription factor that can strongly induce the high expression of target genes in CHO cells. To demonstrate the functionality of this artificial gene expression system and its ability to induce the high expression of target genes in CHO cells, a model antibody (scFv-Fc) was produced using this system. Excellent results were obtained with the plate scale, and when attempting continuous production in semi-continuous cultures using bioreactor tubes with high-cell-density suspension culture using a serum-free medium, high-titer antibody production at the gram-per-liter level was achieved. Shifting the culture temperature to a low temperature of 33 °C achieved scFv-Fc concentrations of up to 5.5 g/L with a specific production rate of 262 pg/(cell∙day). This artificial gene expression system should be a powerful tool for CHO cell engineering aimed at constructing high-yield production systems.

Odontogenic infections in the antibiotic era: approach to diagnosis, management, and prevention.

PURPOSE: The prevalence of odontogenic infections remains one of the highest in the world. If untreated, odontogenic infections can break through the limitation, disseminate to other organs or spaces, and cause high mortality rates. However, it is still difficult to rapidly target limited or disseminated infections in clinical practice. The type of disseminated odontogenic infections and the responsible bacteria have not been described in detail. METHODS: Search databases (e.g., PubMed, MEDLINE, Web of Science, Embase) for reports published from 2018.1 to 2022.9. Use search strategies: ("odontogenic infections" OR "pulpitis" OR "periapical lesions" OR "periodontal diseases") AND ("disseminated infections" OR "complication"). RESULTS: Fourteen different types of disseminated odontogenic infections, most of which are polymicrobial infections, can spread through the body either direct or through hematogenous diffusion. Multiple microbial infections can be more invasive in the transmission of infection. Secondary infections are commonly associated with bacteria like Fusobacterium spp., Streptococcus spp., Peptostreptococcus spp., Prevotella spp., and Staphylococcus spp. Antibiotics with broad-spectrum activity are fundamental as first-line antimicrobial agents based on the microorganisms isolated from disseminated infections. CONCLUSION: This review elaborates on the epidemiology, microorganisms, risk factors, and dissemination routes, and provides evidence-based opinions on the diagnosis, multidisciplinary management, and prevention of odontogenic infections for dentists and clinicians.

Recent advances in nano- and micro-scale carrier systems for controlled delivery of vaccines.

Vaccines provide substantial safety against infectious diseases, saving millions of lives each year. The recent COVID-19 pandemic highlighted the importance of vaccination in providing mass-scale immunization against outbreaks. However, the delivery of vaccines imposes a unique set of challenges due to their large molecular size and low room temperature stability. Advanced biomaterials and delivery systems such as nano- and mciro-scale carriers are becoming critical components for successful vaccine development. In this review, we provide an updated overview of recent advances in the development of nano- and micro-scale carriers for controlled delivery of vaccines, focusing on carriers compatible with nucleic acid-based vaccines and therapeutics that emerged amid the recent pandemic. We start by detailing nano-scale delivery systems, focusing on nanoparticles, then move on to microscale systems including hydrogels, microparticles, and 3D printed microneedle patches. Additionally, we delve into emerging methods that move beyond traditional needle-based applications utilizing innovative delivery systems. Future challenges for clinical translation and manufacturing in this rapidly advancing field are also discussed.

Divergent chondro/osteogenic transduction laws of fibrocartilage stem cell drive temporomandibular joint osteoarthritis in growing mice.

The anterior disc displacement (ADD) leads to temporomandibular joint osteoarthritis (TMJOA) and mandibular growth retardation in adolescents. To investigate the potential functional role of fibrocartilage stem cells (FCSCs) during the process, a surgical ADD-TMJOA mouse model was established. From 1 week after model generation, ADD mice exhibited aggravated mandibular growth retardation with osteoarthritis (OA)-like joint cartilage degeneration, manifesting with impaired chondrogenic differentiation and loss of subchondral bone homeostasis. Lineage tracing using Gli1-CreER+; Tmfl/-mice and Sox9-CreER+;Tmfl/-mice showed that ADD interfered with the chondrogenic capacity of Gli1+ FCSCs as well as osteogenic differentiation of Sox9+ lineage, mainly in the middle zone of TMJ cartilage. Then, a surgically induced disc reposition (DR) mouse model was generated. The inhibited FCSCs capacity was significantly alleviated by DR treatment in ADD mice. And both the ADD mice and adolescent ADD patients had significantly relieved OA phenotype and improved condylar growth after DR treatment. In conclusion, ADD-TMJOA leads to impaired chondrogenic progenitor capacity and osteogenesis differentiation of FCSCs lineage, resulting in cartilage degeneration and loss of subchondral bone homeostasis, finally causing TMJ growth retardation. DR at an early stage could significantly alleviate cartilage degeneration and restore TMJ cartilage growth potential.

Bioinformatics analysis of synovial fluid-derived mesenchymal stem cells in the temporomandibular joint stimulated with IL-1ß.

The stimulation of interleukin-1ß (IL-1ß) is the risk factor for temporomandibular joint osteoarthritis (TMJOA). We aim to investigate IL-1ß stimulation-related gene and signal pathways in synovial fluid-derived mesenchymal stem cells (SF-MSCs) inflammatory activation to predict the occurrence of TMJOA. The microarray dataset GSE150057 was downloaded from the gene expression omnibus (GEO) database, and principal component analysis (PCA) was performed on the involved genes to obtain differential genes (DEGs). Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway were performed based on the DAVID database. The protein-protein interaction (PPI) network was constructed by the STRING database to identify hub genes. Based on the correlation between differential expression levels of lncRNAs and mRNAs, the co-expression network of lncRNA-mRNA was established. A total of 200 DEGs were obtained. Among 168 differential mRNAs, 126 were up-regulated and 42 were down-regulated; among 32 differential lncRNAs, 23 were up-regulated and 9 were down-regulated. Then, GO analysis showed that DEGs were mainly involved in signal transduction, inflammation, and apoptosis processes. KEGG pathway mainly involved the TNF signaling pathway, NF-κB signaling pathway, NOD-like receptor signaling pathway, and cytokine-cytokine-receptor interaction. Ten hub genes were recognized by PPI analysis, including CXCL8, CCL2, CXCL2, NFKBIA, CSF2, IL1A, IRF1, VCAM1, NFKB1, and TNFAIP3. In conclusion, our study has indicated the role of IL-1ß stimulation in the progression of SF-MSCs inflammation and predicted DEGs and downstream pathways.

4D Printing of Personalized-Tunable Biomimetic Periosteum with Anisotropic Microstructure for Accelerated Vascularization and Bone Healing.

An ideal biomimetic periosteum is expected to wrap various bone surfaces to orchestrate an optimal microenvironment for bone regeneration, including facilitating local vascularization, recruiting osteoblasts, and mineralizing the extracellular matrix (ECM). To mimic the role of the natural periosteum in promoting bone repair, a 4D printing technique to inlay aligned cell sheets on shape-shifting hydrogel is used, containing biophysical signals and spatially adjustable physical properties, for the first time. The outer hydrogel layer endows the biomimetic periosteum with the ability to digitally coordinate its 3D geometry to match the specific macroscopic bone shape to maintain a bone healing microenvironment. The inner aligned human mesenchymal stem cells (hMSCs) layer not only promotes the migration and angiogenesis of co-cultured cells but also exhibits excellent osteogenic differentiation properties. In vivo experiments show that apart from morphing preset shapes as physical barriers, the aligned biomimetic periosteum can actively facilitate local angiogenesis and early-stage osteogenesis. Altogether, this present work provides a novel route to construct a personalized biomimetic periosteum with anisotropic microstructure by introducing a tunable shape to maintain the bone reconstruction microenvironment and this strategy can be extended to repair sophisticated bone defects.

Toward Highly Matching the Dura Mater: A Polyurethane Integrating Biocompatible, Leak-Proof, and Self-Healing Properties.

The dura mater is the final barrier against cerebrospinal fluid leakage and plays a crucial role in protecting and supporting the brain and spinal cord. Head trauma, tumor resection and other traumas damage it, requiring artificial dura mater for repair.  However, surgical tears are often unavoidable. To address these issues, the ideal artificial dura mater should have biocompatibility, anti-leakage, and self-healing properties. Herein, this work has used biocompatible polycaprolactone diol as the soft segment and introduced dynamic disulfide bonds into the hard segment, achieving a multifunctional polyurethane (LSPU-2), which integrated the above mentioned properties required in surgery. In particular, LSPU-2 matches the mechanical properties of the dura mater and the biocompatibility tests with neuronal cells demonstrate extremely low cytotoxicity and do not cause any negative skin lesions. In addition, the anti-leakage properties of the LSPU-2 are confirmed by the water permeability tester and the 900 mm H2 O static pressure test with artificial cerebrospinal fluid. Due to the disulfide bond exchange and molecular chain mobility, LSPU-2 could be completely self-healed within 115 min at human body temperature. Thus, LSPU-2 comprises one of the most promising potential artificial dura materials, which is essential for the advancement of artificial dura mater and brain surgery.

Ultraviolet Light-Based Micropattern Printing on Titanium Surfaces to Promote Early Osseointegration.

Patterned interfaces are widely used for surface modification of biomaterials because of a morphological unit similar to that of native tissue. However, engineering fast and cost-effective high-resolution micropatterns directly onto titanium surfaces remains a grand challenge. Herein, a simply designed ultraviolet (UV) light-based micropattern printing to obtain geometrical patterns on implant interfaces is fabricated by utilizing customized photomasks and titanium dioxide (TiO2 ) nanorods as a photo-responsive platform. The technique manipulates the cytoskeleton of micropatterning cells on the surface of TiO2 nanorods. The linear pattern surface shows the elongated morphology and parallel linear arrangements of human mesenchymal stem cells (hMSCs), significantly enhancing their osteogenic differentiation. In addition to the upregulated expression of key osteo-specific function genes in vitro, the accelerated osseointegration between the implant and the host bone is obtained in vivo. Further investigation indicates that the developed linear pattern surface has an outstanding effect on the cytoskeletal system, and finally activates Yes-Associated Protein (YAP)-mediated mechanotransduction pathways, initiating hMSCs osteogenic differentiation. This study not only offers a microfabrication method that can be extended to fabricate various shape- and size-controlled micropatterns on titanium surfaces, but also provides insight into the surface structure design for enhanced bone regeneration.

Mechanical nanosurgery of chemoresistant glioblastoma using magnetically controlled carbon nanotubes.

Glioblastoma (GBM) is the most common and aggressive primary brain cancer. Despite multimodal treatment including surgery, radiotherapy, and chemotherapy, median patient survival has remained at ~15 months for decades. This situation demands an outside-the-box treatment approach. Using magnetic carbon nanotubes (mCNTs) and precision magnetic field control, we report a mechanical approach to treat chemoresistant GBM. We show that GBM cells internalize mCNTs, the mobilization of which by rotating magnetic field results in cell death. Spatiotemporally controlled mobilization of intratumorally delivered mCNTs suppresses GBM growth in vivo. Functionalization of mCNTs with anti-CD44 antibody, which recognizes GBM cell surface-enriched antigen CD44, increases mCNT recognition of cancer cells, prolongs mCNT enrichment within the tumor, and enhances therapeutic efficacy. Using mouse models of GBM with upfront or therapy-induced resistance to temozolomide, we show that mCNT treatment is effective in treating chemoresistant GBM. Together, we establish mCNT-based mechanical nanosurgery as a treatment option for GBM.

Igf1 Regulates Fibrocartilage Stem Cells, Cartilage Growth, and Homeostasis in the Temporomandibular Joint of Mice.

Temporomandibular joint (TMJ) growth requires orchestrated interactions between various cell types. Recent studies revealed that fibrocartilage stem cells (FCSCs) in the TMJ cartilage play critical roles as cell resources for joint development and repair. However, the detailed molecular network that influences FCSC fate during TMJ cartilage development remains to be elucidated. Here, we investigate the functional role of Igf1 in FCSCs for TMJ cartilage growth and homeostasis by lineage tracing using Gli1-CreER+ ; Tmflfl mice and conditional Igf1 deletion using Gli1-/Col2-CreER+ ; Igf1fl/fl mice. In Gli1-CreER+ ; Tmflfl mice, red fluorescence+ (RFP+ ) FCSCs show a favorable proliferative capacity. Igf1 deletion in Gli1+ /Col2+ cell lineages leads to distinct pathological changes in TMJ cartilage. More serious cartilage thickness and cell density reductions are found in the superficial layers in Gli1-CreER+ ; Igf1fl/fl mice. After long-term Igf1 deletion, a severe disordered cell arrangement is found in both groups. When Igf1 is conditionally deleted in vivo, the red fluorescent protein-labeled Gli1+ FCSC shows a significant disruption of chondrogenic differentiation, cell proliferation, and apoptosis leading to TMJ cartilage disarrangement and subchondral bone loss. Immunostaining shows that pAkt signaling is blocked in all cartilage layers after the Gli1+ -specific deletion of Igf1. In vitro, Igf1 deletion disrupts FCSC capacities, including proliferation and chondrogenesis. Moreover, the deletion of Igf1 in FCSCs significantly aggravates the joint osteoarthritis phenotype in the unilateral anterior crossbite mouse model, characterized by decreased cartilage thickness and cell numbers as well as a loss of extracellular matrix secretions. These findings uncover Igf1 as a regulator of TMJ cartilage growth and repair. The deletion of Igf1 disrupts the progenitor capacity of FCSCs, leading to a disordered cell distribution and exaggerating TMJ cartilage dysfunction. © 2023 American Society for Bone and Mineral Research (ASBMR).

A single-cell transcriptional atlas reveals resident progenitor cell niche functions in TMJ disc development and injury.

The biological characteristics of the temporomandibular joint disc involve complex cellular network in cell identity and extracellular matrix composition to modulate jaw function. The lack of a detailed characterization of the network severely limits the development of targeted therapies for temporomandibular joint-related diseases. Here we profiled single-cell transcriptomes of disc cells from mice at different postnatal stages, finding that the fibroblast population could be divided into chondrogenic and non-chondrogenic clusters. We also find that the resident mural cell population is the source of disc progenitors, characterized by ubiquitously active expression of the NOTCH3 and THY1 pathways. Lineage tracing reveals that Myh11+ mural cells coordinate angiogenesis during disc injury but lost their progenitor characteristics and ultimately become Sfrp2+ non-chondrogenic fibroblasts instead of Chad+ chondrogenic fibroblasts. Overall, we reveal multiple insights into the coordinated development of disc cells and are the first to describe the resident mural cell progenitor during disc injury.

Status and Influencing Factors of Physical Exercise among College Students in China: A Systematic Review.

The status of the physical exercise of college students has been a popular topic in China. This study systematically reviewed the exercise status of Chinese college students and its influencing factors. A keyword and reference search were conducted in the Web of Science, PubMed, Cochrane library, and the China National Knowledge Infrastructure. Additionally, Google Scholar was searched to collect literatures related to physical activity of Chinese university students published in Chinese and English from 1 January 2017 to 30 July 2022. Fifteen studies met the selection criteria and were included in the review. The results show that the main motivation for Chinese college students to exercise is to strengthen their bodies, with running and walking ranking first and ball games ranking second in importance. Most of the college students exercised three times a week, which is the recommended minimum, and most of their workouts were of moderate intensity. Additionally, the workouts lasted for 30 min to 60 min. The main factors affecting college students' exercise are lack of time due to academic pressure, facilities constraints, and lack of professional exercise guidance. In conclusion, the physical fitness of university students should not be underestimated, and this study provides additional reference to promote healthier lifestyles among Chinese college students.

Mucosa-interfacing electronics.

The surface mucosa that lines many of our organs houses myriad biometric signals and, therefore, has great potential as a sensor-tissue interface for high-fidelity and long-term biosensing. However, progress is still nascent for mucosa-interfacing electronics owing to challenges with establishing robust sensor-tissue interfaces; device localization, retention and removal; and power and data transfer. This is in sharp contrast to the rapidly advancing field of skin-interfacing electronics, which are replacing traditional hospital visits with minimally invasive, real-time, continuous and untethered biosensing. This Review aims to bridge the gap between skin-interfacing electronics and mucosa-interfacing electronics systems through a comparison of the properties and functions of the skin and internal mucosal surfaces. The major physiological signals accessible through mucosa-lined organs are surveyed and design considerations for the next generation of mucosa-interfacing electronics are outlined based on state-of-the-art developments in bio-integrated electronics. With this Review, we aim to inspire hardware solutions that can serve as a foundation for developing personalized biosensing from the mucosa, a relatively uncharted field with great scientific and clinical potential.

Technical Skills to Split Teeth During Extraction of Mesiodentes in High Site.

PURPOSE: Extraction of mesiodens in high site is complicated. Here we introduce some technical skills to simply the process and achieve high success rate meanwhile. METHODS: All patients should accept radiographic examination before surgery. According to the position of mesiodens based on cone-beam computed tomography, we choose the appropriate method and tool. RESULTS: A series of cases have proved that these skills are applicable and convenient. CONCLUSIONS: Dentists should analyze the inspection results seriously and select the optimal strategy to extract mesiodens in high site.

A Seldom Seen Complication in the Inferior Alveolar Nerve Block.

PURPOSE: Introduce Kuhn anemia as a complication during the inferior alveolar nerve block (IANB). METHODS: Here, the authors reported a lesser-known complication called Kuhn anemia during the IANB. Then, the authors searched and reviewed relevant literature on the Web of Science. RESULTS: Vasospasm of the maxillary artery results in the phenomenon. Reasons, such as inaccurate injection, anatomical variation, drug diffusion, and so on, may account for the complication during the IANB. CONCLUSIONS: All in all, doctors should be prudent before and during the surgery.

Thinning intensity but not replanting different species affects soil N2O and CH4 fluxes in Cunninghamia lanceolata plantation.

Thinning and replanting are effective forest management measures to improve the stand structure and species composition of artificial forests. However, the effects of thinning and replanting on soil N2O and CH4 fluxes and their associations with changes in soil environment factors have been poorly understood in plantation forests. A 36-month field experiment was conducted to elucidate the effects of thinning and replanting different species on soil N2O and CH4 fluxes and related environmental factors in Cunninghamia lanceolata plantation on shallow soil. The experiment consisted of five treatments, uncut control (CK), moderate thinning + replanting evergreen seedlings (MTE), moderate thinning + replanting deciduous seedlings (MTD), heavy thinning + replanting evergreen seedlings (HTE), heavy thinning + replanting deciduous seedlings (HTD). Compared with the control, moderate and heavy thinning increased cumulative N2O emissions by 12.4% and 21.4%, respectively, and reduced CH4 cumulative uptake by 35.4% and 38.8%, respectively. However, the effects on soil N2O and CH4 fluxes replanting deciduous or evergreen seedlings were insignificant. The results showed that thinning increased N2O emissions and decreased CH4 uptake due to the increased soil temperature, labile C and N concentrations. Soil temperature was the dominant factor, and mineral N was a contributing factor affecting N2O and CH4 fluxes. The study concludes that thinning increased the global warming potential with N2O contributing more than CH4 (113.5%: -13.5%). Our findings highlight that thinning increased N2O emissions and decreased CH4 uptake with the increasing intensity and the replanting had no different effects between deciduous and evergreen seedlings on the fluxes of N2O and CH4 during the early years following thinning.

A Potential Complication After Drainage in Odontogenic Descending Necrotizing Mediastinitis: Chyle Leakage.

ABSTRACT: Descending necrotizing mediastinitis is a serious complication of odontogenic infections. Incision and drainage of the maxillofacial infection with mediastinal drainage represent the principal management. However, chyle leakage after drainage in descending necrotizing mediastinitis is rare and has not been reported. Here the authors present a case of a 74-year-old man with chyle leakage after mediastinal drainage, which is successfully treated.

The association between low birth weight and dental caries among 11-to-13-year-old school age children in Ningbo, China.

BACKGROUND: The association between low birth weight (LBW) and dental caries is currently unclear. The aim of this study was to investigate the association of LBW with dental caries in permanent teeth in children of Ningbo city. METHODS: A total of 1975 children aged 11-to-13 years in Ningbo, China were enrolled in this cross-sectional study. LBW was defined as a birthweight< 2500 g. Ten dentists assessed the status of dental caries in permanent teeth in line with the World Health Organization (WHO) criteria and guidelines. Decayed, missing or filled teeth were considered to have dental caries. Parental questionnaires were used to collect child information. Non-conditional logistic regression analysis was used to estimate odds ratios (ORs) and the corresponding 95% confidence intervals (CIs). RESULTS: Dental caries in permanent teeth was found in 610 children (30.9%), with a mean DMFS of 2.09 (SD = 1.2). The adjusted ORs for dental caries in permanent teeth was 1.46 (95% CI 1.00, 2.13) for LBW. CONCLUSIONS: LBW was not associated with dental caries in permanent teeth in the study population.