Modulation of macrophages by a phillyrin-loaded thermosensitive hydrogel promotes skin wound healing in mice.

BACKGROUND: Impaired wound healing in traumatic skin injuries remains a severe clinical challenge due to impaired re-vascularization, harmful bacteria infection, and inflammation dysregulation. Macrophages are recognized as prominent immune cells in tissue regeneration and wound healing. Consequently, the modulation of macrophages provides a promising therapeutic target for wound healing disorders. Here, we aimed to explore whether a novel constructed combination of thermosensitive hydrogel Pluronic F-127 (PF-127) and phillyrin (PH, the main active compound of forsythia suspensa) could improve skin wound healing. METHODS: Firstly, the biological effects of pH on the phenotype and inflammation of macrophages were assessed by flow cytometry and ELISA. The biocompatibility of the PF-127 plus PH combination was investigated on keratinocytes and red blood cells. The biological effect of PF-127/PH hydrogel on the migratory ability of keratinocytes in vitro was evaluated using the scratch and transwell migration assays. In addition,S. aureusandE. coliwere employed to test the antibacterial properties of the PF-127 plus PH combination. Finally, PF-127 plus PH scaffold was appliedto the full-thickness skin defect in mice. Histomorphological evaluation and immunochemistry were performed to explore the wound-healing activity of PF-127/PH hydrogel. RESULTS: PH can promote the polarization of macrophages from the M1 (pro-inflammatory) phenotype to the M2 (anti-inflammatory) phenotype. The PF-127/PH hydrogel was highly biocompatible and showed a potent stimulative effect on the migration of keratinocytesin vitro. The combination of PF-127 and PH exerted a pronounced antibacterial activity onS. aureusandE. coli in vitro.PF-127/PH hydrogel potently accelerates the healing of full-thickness skin defects by promoting skin cell proliferation, accelerating angiogenesis, and inhibiting inflammation. CONCLUSIONS: Our study suggests that PF-127/PH hydrogel has excellent potential for treating traumatic skin defects.

Molecularly imprinted polymer-based SERS sensing of transferrin in human serum.

Specific detection of glycoproteins such as transferrin (TRF) related to neurological diseases, hepatoma and other diseases always plays an important role in the field of disease diagnosis. We designed an antibody-free immunoassay sensing method based on molecularly imprinted polymers (MIPs) formed by the polymerization of multiple functional monomers for the sensitive and selective detection of TRF in human serum. In the sandwich surface-enhanced Raman spectroscopy (SERS) sensor, the TRF-oriented magnetic MIP nanoparticles (Fe3O4@SiO2-MIPs) served as capture units to specifically recognize TRF and 4-mercaptophenylboronic acid-functionalized gold nanorods (MPBA-Au NRs) served as SERS probes to label the targets. In order to achieve stronger interaction between the recognition cavities of the prepared MIPs and the different amino acid fragments that make up TRF, Fe3O4@SiO2-MIPs were obtained through polycondensation reactions between more silylating reagents, enhancing the specific recognition of the entire TRF protein and achieving high IF. This sensing method exhibited a good linear response to TRF within the TRF concentration range of 0.01 ng mL-1 to 1 mg mL-1 (R2 = 0.9974), and the LOD was 0.00407 ng mL-1 (S/N = 3). The good stability, reproducibility and specificity of the resulting MIP based SERS sensor were demonstrated. The determination of TRF in human serum confirmed the feasibility of the method in practical applications.

Small-Intensity Rainfall Triggers Greater Contamination of Rubber-Derived Chemicals in Road Stormwater Runoff from Various Functional Areas in Megalopolis Cities.

Rubber-derived chemicals (RDCs) originating from tire and road wear particles are transported into road stormwater runoff, potentially threatening organisms in receiving watersheds. However, there is a lack of knowledge on time variation of novel RDCs in runoff, limiting initial rainwater treatment and subsequent rainwater resource utilization. In this study, we investigated the levels and time-concentration profiles of 35 target RDCs in road stormwater runoff from eight functional areas in the Greater Bay Area, South China. The results showed that the total concentrations of RDCs were the highest on the expressway compared with other seven functional areas. N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD), 6PPD-quinone, benzothiazole, and 1,3-diphenylguanidine were the top four highlighted RDCs (ND-228840 ng/L). Seasonal and spatial differences revealed higher RDC concentrations in the dry season as well as in less-developed regions. A lag effect of reaching RDC peak concentrations in road stormwater runoff was revealed, with a lag time of 10-90 min on expressways. Small-intensity rainfall triggers greater contamination of rubber-derived chemicals in road stormwater runoff. Environmental risk assessment indicated that 35% of the RDCs posed a high risk, especially PPD-quinones (risk quotient up to 2663). Our findings contribute to a better understanding of managing road stormwater runoff for RDC pollution.

Defining raft domains in the plasma membrane.

Many plasma membrane (PM) functions depend on the cholesterol concentration in the PM in strikingly nonlinear, cooperative ways: fully functional in the presence of physiological cholesterol levels (35~45 mol%), and nonfunctional below 25 mol% cholesterol; namely, still in the presence of high concentrations of cholesterol. This suggests the involvement of cholesterol-based complexes/domains formed cooperatively. In this review, by examining the results obtained by using fluorescent lipid analogs and avoiding the trap of circular logic, often found in the raft literature, we point out the fundamental similarities of liquid-ordered (Lo)-phase domains in giant unilamellar vesicles, Lo-phase-like domains formed at lower temperatures in giant PM vesicles, and detergent-resistant membranes: these domains are formed by cooperative interactions of cholesterol, saturated acyl chains, and unsaturated acyl chains, in the presence of >25 mol% cholesterol. The literature contains evidence, indicating that the domains formed by the same basic cooperative molecular interactions exist and play essential roles in signal transduction in the PM. Therefore, as a working definition, we propose that raft domains in the PM are liquid-like molecular complexes/domains formed by cooperative interactions of cholesterol with saturated acyl chains as well as unsaturated acyl chains, due to saturated acyl chains' weak multiple accommodating interactions with cholesterol and cholesterol's low miscibility with unsaturated acyl chains and TM proteins. Molecules move within raft domains and exchange with those in the bulk PM. We provide a logically established collection of fluorescent lipid probes that preferentially partition into raft and non-raft domains, as defined here, in the PM.

Core-satellite surface imprinting polymer-based pipette tip solid-phase extraction for the colorimetric determination of pyrethroid metabolite.

A core-satellite-structured surface molecularly imprinted polymer has been synthesized for the enrichment of 3-phenoxybenzaldehyde by pipette tip solid-phase extraction (SPE). In a typical sol-gel process, two silane reagents as functional monomers and 3-phenoxybenzoic acid as the dummy template, the surface imprinting layer was coated on the core-satellite silica microsphere, which formed the core-satellite-structured molecularly imprinted polymer (CSMIP). Compared to the silica-based core-shell ones, this CS-MIP exhibits a stunning surface area (142 m2 g-1) in micrometer size and also overcomes the aggregation trends of core-shell structure in nanoscale. Taking potassium permanganate solution as oxidizer and indicator, the adsorbed 3-phenoxybenzaldehyde can be a quantitatively determined through redox reaction after elution. The value of maximum adsorption capacity and imprinting factor of CS-MIP were calculated to be 87.5 µg mg-1 and 2.13, respectively. These CS-MIPs were packed into commercial pipette tip as the sorbent to concentrate 3-phenoxybenzaldehyde. Under the optimum condition, a liner relationship was achieved in the range 0.200 to 1.00 µg mL-1 and the limit of detection was 81 ng mL-1. Moreover, this customized SPE device exhibits good adsorption capability after six sequential adsorption-desorption cycles, and the high recovery range of 92.2~99.7% of spiked tap water assay demonstrated its potential application for real sample analysis. Graphical abstract Schematic presentation of core-satellite molecularly imprinted polymer preparation strategy and customized pipette tip solid-phase extraction device.

Contributions of Bioactive Molecules in Stem Cell-Based Periodontal Regeneration.

Periodontal disease is a widespread disease, which without proper treatment, may lead to tooth loss in adults. Because stem cells from the inflammatory microenvironment created by periodontal disease exhibit impaired regeneration potential even under favorable conditions, it is difficult to obtain satisfactory therapeutic outcomes using traditional treatments, which only focus on the control of inflammation. Therefore, a new stem cell-based therapy known as cell aggregates/cell sheets technology has emerged. This approach provides sufficient numbers of stem cells with high viability for treating the defective site and offers new hope in the field of periodontal regeneration. However, it is not sufficient for regenerating periodontal tissues by delivering cell aggregates/cell sheets to the impaired microenvironment in order to suppress the function of resident cells. In the present review, we summarize some promising bioactive molecules that act as cellular signals, which recreate a favorable microenvironment for tissue regeneration, recruit endogenous cells into the defective site and enhance the viability of exogenous cells.

Tooth loss and metabolic syndrome in middle-aged Japanese adults.

AIM: Metabolic syndrome is associated with periodontal disease and dental caries; however, little attention has been given to the association between metabolic syndrome and tooth loss, which is the endpoint of these two diseases. This study examined this association in middle-aged adults over a 5-year period. METHODS: A retrospective study was performed in 2107 participants (1718 males and 389 females) aged 35-60 years who underwent annual dental check-ups, to evaluate tooth loss and metabolic components, including obesity, elevated triglycerides, blood pressure, fasting glucose, and reduced high-density lipoprotein. Logistic regression analysis was performed to evaluate the association between metabolic syndrome (≥3 components) at the baseline examination and tooth loss. RESULTS: Over a 5-year period, 10.8% of the participants lost at least one tooth. Compared to those with no metabolic components, participants with ≥3 components had an increased risk of tooth loss (odds ratio = 1.54; 95% confidence interval: 1.01-2.37), adjusting for age, gender, dental caries experience, attachment loss, oral hygiene status, number of teeth, tooth brushing frequency, smoking, and occupational status. CONCLUSIONS: Metabolic syndrome was associated with the incidence of tooth loss among middle-aged adults.

Identification of a novel PHEX mutation in a Chinese family with X-linked hypophosphatemic rickets using exome sequencing.

Familial hypophosphatemic rickets (HR), the most common inherited form of rickets, is a group of inherited renal phosphate wasting disorders characterized by growth retardation, rickets with bone deformities, osteomalacia, poor dental development, and hypophosphatemia. The purpose of this study was to identify the genetic defect responsible for familial HR in a four-generation Chinese Han pedigree by exome sequencing and Sanger sequencing. Clinical features include skeletal deformities, teeth abnormalities, hearing impairments and variable serum phosphate level in patients of this family. A novel deletion mutation, c.1553delT (p.F518Sfs*4), was identified in the X-linked phosphate regulating endopeptidase homolog gene (PHEX). The mutation is predicted to result in prematurely truncated and loss-of-function PHEX protein. Our data suggest that exome sequencing is a powerful tool to discover mutation(s) in HR, a disorder with genetic and clinical heterogeneity. The findings may also provide new insights into the cause and diagnosis of HR, and have implications for genetic counseling and clinical management.

The permeability of puerarin loaded poly(butylcyanoacrylate) nanoparticles coated with polysorbate 80 on the blood-brain barrier and its protective effect against cerebral ischemia/reperfusion injury.

Puerarin (PUE) is a good candidate for treating stroke, but its low concentration in brain after administration limits its curative efficacy. The aim of the present work was to design and characterize PUE loaded poly(butylcyanoacrylate) nanoparticles (PBCN) coated with polysorbate 80 (Ps 80), and to evaluate the effect of PBCN on the permeability of PUE across the blood-brain barrier (BBB) and the effect of PUE loaded PBCN on the cerebral ischemia/reperfusion injury. PUE loaded PBCN were successfully prepared by anionic polymerization method with the mean particle size of 201.2 nm and the zeta potential of -7.72 mV. The in vitro release behavior of PUE from the nanoparticles showed a biphasic profile manner with an initial burst release followed by a sustained release. The results of pharmacokinetic and biodistribution to brain performed in mice after intravenous administration showed that the drug concentrations in blood and brain for PUE loaded PBCN were both greater than these for the free drug. Moreover, compared with free drug, the vein injection of PUE loaded PBCN exerted the better neuroprotective effect in rats with focal cerebral ischemic injury via significantly decreasing neurological deficit scores, increasing body weight, lowing brain water content, and reducing the infarct volume. The results indicated that this preparation may reduce the total dose required for the stroke therapy with concurrent reduction in dose related toxicity. All these findings suggest that PBCN could enhance the transport of PUE to brain and have a potential as a neuroprotective agent in the focal cerebral ischemic injury.

Bimetallic MOFs loaded cellulose as an environment friendly bioadsorbent for highly efficient tetracycline removal.

Due to the increasingly serious antibiotic-related pollution, it is crucial to develop novel green bioadsorbents to effectively remove antibiotics from aqueous solutions. In this study, Fe doped zeolitic imidazolate frameworks-8 loaded cellulose (Fe/ZIF-8@cellulose) aerogels were prepared. The synthesized Fe/ZIF-8@cellulose aerogels were characterized experimentally including morphology observation and chemical compositions determination. The effects of bioadsorbent dosage, solution pH, adsorption time, initial TC concentration and adsorption temperature on the TC adsorption behaviors were systematically studied. Due to the introduction of Fe in the ZIF-8, the maximum adsorption capacity of Fe/ZIF-8@cellulose for TC could reach as high as 1359.2 mg/g, which is higher than the reported ZIF-8 loaded polysaccharide based adsorbents. The adsorption kinetics and isotherm of TC adsorption were also determined. With the cellulose as the matrix to load Fe/ZIF-8, the obtained Fe/ZIF-8@cellulose aerogels exhibited good reusability. Most importantly, the TC adsorption mechanism was proposed. The results of our finding suggest that the Fe doping into MOFs is an effective strategy to improve the antibiotics adsorption performance and the application of cellulose as the matrix is a valuable method to increase the cyclic utilization. This study highlights the potentials of applying the Fe/ZIF-8@cellulose aerogels in the antibiotics removal for practical wastewater.

Distribution and variation of metals in urban river sediments in response to microplastics presence, catchment characteristics and sediment properties.

Despite well documented studies on metal pollutants in aquatic ecosystems, knowledge on the combined effects of catchment characteristics, sediment properties, and emerging pollutants, such as microplastics (MPs) on the presence of metals in urban river sediments is still limited. In this study, the synergistic influence of MPs type and hazard indices, catchment characteristics and sediment properties on the variability of metals present in sediments was investigated based on a typical urban river, Brisbane River, Australia. It was noted that the mean concentrations of metals in Brisbane River decreases in the order of Al (94,142 ± 12,194 µg/g) > Fe (62,970 ± 8104 µg/g) > Mn (746 ± 258 µg/g) > Zn (196 ± 29 µg/g) > Cu (50 ± 19 µg/g) > Pb (47 ± 25 µg/g) > Ni (25 ± 3 µg/g) while the variability of metals decreases in the order of Pb > Cu > Mn > Al > Ni > Zn > Fe along the river. According to enrichment factor (Ef) contamination categories, Mn, Cu and Zn exert a moderate level of contamination (Ef > 2), while Fe, Ni, and Zn show slight sediment pollution (1 3) was found at sampling locations having a high urbanisation level and traffic related activities. Crustal metal elements (namely, Al, Fe, Mn) were found to be statistically significantly correlated with sediment properties (P < 0.05). Anthropogenic source metals (namely, Cu, Ni, Pb, Zn) were observed to be highly correlated with catchment characteristics. Additionally, the presence of metals in sediments were positively correlated with MPs concentration, and negatively correlated with MPs hazard indices. The outcomes of this study provide new insights for understanding the relationships among metals and various influential factors in the context of urban river sediment pollution, which will benefit the formulation of risk assessment and regulatory measures for protecting urban waterways.

Multiple Recurrent Infective Endocarditis Secondary to Streptococcus mitis Bacteremia Despite Proper Antibiotic and Surgical Treatment.

Infective endocarditis (IE) is a rare and potentially fatal disease. It is an infection of the endocardium of the heart and heart valves. One of the major complications faced by patients who have recovered from a first episode of IE is recurrent IE. Risk factors for recurrent IE include intravenous (IV) drug use, prior episodes of IE, poor dentition, recent dental procedures, male gender, age over 65, prosthetic heart valve endocarditis, chronic dialysis, positive valve culture(s) obtained at the time of surgical intervention, and persistent postoperative fever. We present a case of a 40-year-old male with a history of former IV heroin use who experienced multiple episodes of recurrent IE caused by the same pathogen, Streptococcus mitis. This recurrence occurred despite the patient completing the appropriate course of antibiotic therapy, undergoing valvular replacement, and maintaining drug abstinence for two years. This case highlights the challenges associated with identifying the source of infection and emphasizes the need to develop guidelines for surveillance and prophylaxis against recurrent IE.

Bisphosphonates and Their Connection to Dental Procedures: Exploring Bisphosphonate-Related Osteonecrosis of the Jaws.

Bisphosphonates are widely used to treat osteoporosis and malignant tumors due to their effectiveness in increasing bone density and inhibiting bone resorption. However, their association with bisphosphonate-related osteonecrosis of the jaws (BRONJ) following invasive dental procedures poses a significant challenge. This review explores the functions, mechanisms, and side effects of bisphosphonates, emphasizing their impact on dental procedures. Dental patients receiving bisphosphonate treatment are at higher risk of BRONJ, necessitating dentists' awareness of these risks. Topical bisphosphonate applications enhance dental implant success, by promoting osseointegration and preventing osteoclast apoptosis, and is effective in periodontal treatment. Yet, systemic administration (intravenous or intraoral) significantly increases the risk of BRONJ following dental procedures, particularly in inflamed conditions. Prevention and management of BRONJ involve maintaining oral health, considering alternative treatments, and careful pre-operative and post-operative follow-ups. Future research could focus on finding bisphosphonate alternatives with fewer side effects or developing combinations that reduce BRONJ risk. This review underscores the need for further exploration of bisphosphonates and their implications in dental procedures.

Highly efficient SO2 absorption/activation and subsequent utilization by polyethylene glycol-functionalized Lewis basic ionic liquids.

Up to now, flue-gas desulfurization (FGD) is one of the most effective techniques to control SO(2) emission from the combustion of fossil fuels. The conventional technology for FGD poses serious inherent drawbacks such as formation of byproducts and volatilization of solvents. In this work, polyethylene glycol (PEG)-functionalized Lewis basic ionic liquids (ILs) derived from DABCO were proved to be highly efficient absorbents for FGD due to its specific features such as high thermal stability, negligible vapor pressure, high loading capacity. Notably, PEG(150)MeDABCONTf(2) gave an extremely high SO(2) capacity (4.38 mol mol(-1) IL), even under 0.1 bar SO(2) partial pressure (1.01 mol mol(-1) IL), presumably owing to the strong SO(2)-philic characterization of the PEG chain. Furthermore, the absorbed SO(2) could be easy to release by just bubbling N(2) at room temperature, greatly reducing energy requirement for SO(2) desorption. In addition, SO(2)/CO(2) selectivity (110) of PEG(150)MeDABCONTf(2) is two times larger than the non-functionalized imidazolium IL (45). On the other hand, through activation of SO(2) with the tertiary nitrogen in the cation, Lewis basic ILs such as PEG(150)MeDABCOBr proved to be efficient catalysts for the conversion of SO(2) to some value-added chemicals such as cyclic sulfites without utilization of any organic solvent or additive. Thus, this protocol would pave the way for the development of technological innovation towards efficient and low energy demanded practical process for SO(2) absorption and subsequent transformation.

Risk associated with microplastics in urban aquatic environments: A critical review.

The presence of microplastics (MPs) has been recognized as a significant environmental threat due to adverse effects spanning from molecular level, organism health, ecosystem services to human health and well-being. MPs are complex environmental contaminants as they bind to a wide range of other contaminants. MPs associated contaminants include toxic chemical substances that are used as additives during the plastic manufacturing process and adsorbed contaminants that co-exist with MPs in aquatic environments. With the transfer between the water column and sediments, and the migration within aquatic systems, such contaminants associated MPs potentially pose high risk to aquatic systems. However, only limited research has been undertaken currently to link the environmental risk associated with MPs occurrence and movement behaviour in aquatic systems. Given the significant environmental risk and current knowledge gaps, this review focuses on the role played by the abundance of different MP species in water and sediment compartments as well as provides the context for assessing and quantifying the multiple risks associated with the occurrence and movement behaviour of different MP types. Based on the review of past literature, it is found that the physicochemical properties of MPs influence the release/sorption of other contaminants and current MPs transport modelling studies have primarily focused on virgin plastics rather than aged plastics. Additionally, risk assessment of contaminants-associated MPs needs significantly more research. This paper consolidates the current state-of-the art knowledge on the source to sink movement behaviour of MPs and methodologies for assessing the risk of different MP species. Moreover, knowledge gaps and emerging trends in the field are also identified for future research endeavours.

Chondroitin sulfate microspheres anchored with drug-loaded liposomes play a dual antioxidant role in the treatment of osteoarthritis.

Reactive oxygen species (ROS) play a critical role in the pathogenesis of osteoarthritis. The injection of a single antioxidant drug is characterized by low drug utilization and short residence time in the articular cavity, limiting the therapeutic effect of antioxidant drugs on osteoarthritis. Currently, the drug circulation half-life can be extended using delivery vehicles such as liposomes and microspheres, which are widely used to treat diseases. In addition, the composite carriers of liposomes and hydrogel microspheres can combine the advantages of different material forms and show stronger plasticity and flexibility than traditional single carriers, which are expected to become new local drug delivery systems. Chondroitin sulfate, a sulfated glycosaminoglycan commonly found in native cartilage, has good antioxidant properties and degradability and is used to develop an injectable chondroitin sulfate hydrogel by covalent modification with photo-cross-linkable methacryloyl groups (ChsMA). Herein, ChsMA microgels anchored with liquiritin (LQ)-loaded liposomes (ChsMA@Lipo) were developed to delay the progression of osteoarthritis by dual antioxidation. On the one hand, the antioxidant drug LQ wrapped in ChsMA@Lipo microgels exhibits significant sustained-release kinetics due to the double obstruction of the lipid membrane and the hydrogel matrix network. On the other hand, ChsMA can eliminate ROS through degradation into chondroitin sulfate monomers by enzymes in vivo. Therefore, ChsMA@Lipo, as a degradable and dual antioxidant drug delivery platform, is a promising option for osteoarthritis treatment. STATEMENT OF SIGNIFICANCE: Compared with the traditional single carrier, the composite carriers of hydrogel microspheres and liposome can complement the advantages of different materials, which shows stronger plasticity and flexibility, and is expected to become a new and efficient drug delivery system. ChsMA@Lipo not only attenuates IL-1ß-induced ECM degradation in chondrocytes but also inhibits the M1 macrophages polarization and the inflammasome activation. The obtained ChsMA@Lipo alleviates the progression of osteoarthritis in vivo, which is promising for osteoarthritis treatment.

Responsive hyaluronic acid-gold cluster hybrid nanogel theranostic systems.

Tumor microenvironment responsive and self-monitored multimodal synergistic theranostic strategies can significantly improve therapeutic efficacy by overcoming biological barriers. Herein, we report a type of smart fluorescent hyaluronic acid nanogel that can respond to the reducing microenvironment and activate tumor targeting with light-traceable monitoring in cancer therapy. First, the derivative of hyaluronic acid (HA) with a vinyl group and cystamine bisacrylamide were used to synthesize bioreducible HA based nanogels via copolymerization in aqueous medium. Then, multifunctional mHA-gold cluster (mHA-GC) hybrid nanogels were successfully prepared by the in situ reduction of gold salt in the HA nanogels. The HA matrix turns the nanogels into a capsule for effective drug loading with excellent colloidal stability. Interestingly, the reducing tumor microenvironment dramatically enhanced the fluorescence signal of gold clusters in the hybrid nanogels. The highly selective cancer cell uptake and efficient intratumoral accumulation of the hybrid nanogels were demonstrated by fluorescence tracking of these nanogels. Responsive disassembly of the hybrid nanogels and drug release were triggered by excess glutathione presence in cancer cells. Moreover, in vivo and in vitro tumor suppression assays revealed that the doxorubicin-loaded hybrid nanogels exhibited significantly superior tumor cell inhibition abilities compared to free DOX. Overall, the mHA-GC hybrid nanogels emerge as a promising theranostic nanoplatform for the targeted delivery and controlled release of antitumor drugs with light-traceable monitoring in cancer treatment.

Biodegradable intramedullary nail (BIN) with high-strength bioceramics for bone fracture.

About 10 million fractures occur worldwide each year, of which more than 60% are long bone fractures. It is generally agreed that intramedullary nails have significant advantages in rigid fracture fixation. Metal intramedullary nails (INs) can provide strong support but a stress shielding effect can occur that results in nonunion healing in clinic. Nondegradable metals also need to be removed by a second operation. Could INs be biodegradable and used to overcome this issue? As current degradable biomaterials always suffer from low strength and cannot be used in Ins, herein, we report a novel device consisting of biodegradable IN (BIN) made for the first time with bioceramics. These BINs have an extremely high bending strength and stable internal and external structure. Experiments show that the BINs could not only fix and support the tibial fracture model, but also promote osteogenesis and affect the microenvironment of the bone marrow cavity. Therefore, they could be expected to replace traditional metal IN and become a more effective treatment option for tibial fractures.

Gli1+ Cells Residing in Bone Sutures Respond to Mechanical Force via IP3R to Mediate Osteogenesis.

Early orthodontic correction of skeletal malocclusion takes advantage of mechanical force to stimulate unclosed suture remodeling and to promote bone reconstruction; however, the underlying mechanisms remain largely unclear. Gli1+ cells in maxillofacial sutures have been shown to participate in maxillofacial bone development and damage repair. Nevertheless, it remains to be investigated whether these cells participate in mechanical force-induced bone remodeling during orthodontic treatment of skeletal malocclusion. In this study, rapid maxillary expansion (RME) mouse models and mechanical stretch loading cell models were established using two types of transgenic mice which are able to label Gli1+ cells, and we found that Gli1+ cells participated in mechanical force-induced osteogenesis both in vivo and in vitro. Besides, we found mechanical force-induced osteogenesis through inositol 1,4,5-trisphosphate receptor (IP3R), and we observed for the first time that inhibition of Gli1 suppressed an increase in mechanical force-induced IP3R overexpression, suggesting that Gli1+ cells participate in mechanical force-induced osteogenesis through IP3R. Taken together, this study is the first to demonstrate that Gli1+ cells in maxillofacial sutures are involved in mechanical force-induced bone formation through IP3R during orthodontic treatment of skeletal malocclusion. Furthermore, our results provide novel insights regarding the mechanism of orthodontic treatments of skeletal malocclusion.

Comparative evaluation of treatment plan quality for a prototype biology-guided radiotherapy system in the treatment of nasopharyngeal carcinoma.

We aimed to compare prototype treatment plans for a new biology-guided radiotherapy (BgRT) machine in its intensity-modulated radiation therapy (IMRT) mode with those using existing IMRT delivery techniques in treatment of nasopharyngeal carcinoma (NPC). We retrospectively selected ten previous NPC patients treated in 33 fractions according to the NRG-HN001 treatment protocol. Three treatment plans were generated for each patient: a helical tomotherapy (HT) plan with a 2.5-cm jaw, a volumetric modulated arc therapy (VMAT) plan using 2 to 4 6-MV arc fields, and a prototype IMRT plan for a new BgRT system which uses a 6-MV photon beam on a ring gantry that rotates at 60 rotations per minute with a couch that moves in small incremental steps. Treatment plans were compared using dosimetric parameters to planning target volumes (PTVs) and organs at risk (OARs) as specified by the NRG-HN001 protocol. Plans for the three modalities had comparable dose coverage, mean dose, and dose heterogeneity to the primary PTV, while the prototype IMRT plans had greater dose heterogeneity to the non-primary PTVs, with the average homogeneity index ranging from 1.28 to 1.50 in the prototype plans. Six of all the 7 OAR mean dose parameters were lower with statistical significance in the prototype plans compared to the HT and VMAT plans with the other mean dose parameter being comparable, and all the 18 OAR maximum dose parameters were comparable or lower with statistical significance in the prototype plans. The average left and right parotid mean doses in the prototype plans were 10.5 Gy and 10.4 Gy lower than those in the HT plans, respectively, and were 5.1 Gy and 5.2 Gy lower than those in the VMAT plans, respectively. Compared to that with the HT and VMAT plans, the treatment time was longer with statistical significance with the prototype IMRT plans. Based on dosimetric comparison of ten NPC cases, the prototype IMRT plans achieved comparable or better critical organ sparing compared to the HT and VMAT plans for definitive NPC radiotherapy. However, there was higher dose heterogeneity to non-primary targets and longer estimated treatment time with the prototype plans.