Seroprevalence and molecular detection of Toxoplasma gondii and Neospora caninum in beef cattle and goats in Hunan province, China.

BACKGROUND: Toxoplasma gondii and Neospora caninum are closely related protozoan parasites that are considered important causes of abortion in livestock, causing huge economic losses. Hunan Province ranks 12th in the production of beef and mutton in China. However, limited data are available on the seroprevalence, risk factors and molecular characterization of T. gondii and N. caninum in beef cattle and goats in Hunan province, China. METHODS: Sera of 985 beef cattle and 1147 goats were examined for the presence of specific antibodies against T. gondii using indirect hemagglutination test (IHAT) and anti-N. caninum IgG using competitive-inhibition enzyme-linked immunoassay assay (cELISA). Statistical analysis of possible risk factors was performed using PASW Statistics. Muscle samples of 160 beef cattle and 160 goats were examined for the presence of T. gondii DNA (B1 gene) and N. caninum DNA (Nc-5 gene) by nested PCR. The B1 gene-positive samples were genotyped at 10 genetic markers using the multilocus nested PCR-RFLP (Mn-PCR-RFLP). RESULTS: Specific IgG against T. gondii were detected in 8.3% (82/985) and 13.3% (153/1147) and against N. caninum in 2.1% (21/985) and 2.0% (23/1147) of the beef cattle and goats, respectively. Based on statistical analysis, the presence of cats, semi-intensive management mode and gender were identified as significant risk factors for T. gondii infection in beef cattle. Age was a significant risk factor for T. gondii infection in goats (P < 0.05), and age > 3 years was a significant risk factor for N. caninum infection in beef cattle (P < 0.05). PCR positivity for T. gondii was observed in three beef samples (1.9%; 3/160) and seven chevon samples (4.4%; 7/160). Genotyping of PCR positive samples identified one to be ToxoDB#10. The N. caninum DNA was observed in one beef sample (0.6%; 1/160) but was negative in all chevon samples. CONCLUSIONS: To our knowledge, this is the first large-scale serological and molecular investigation of T. gondii and N. caninum and assessment of related risk factors in beef cattle and goats in Hunan Province, China. The findings provide baseline data for executing prevention and control of these two important parasites in beef cattle and goats in China.

Survival-weighted quality of life profiles in patients treated for laryngeal and hypopharyngeal cancers.

Objectives: This study assessed functional outcomes and quality of life (QoL) in the long term in individuals treated for laryngohypopharyngeal cancer (LHC) by estimating their life expectancy (LE), survival-weighted psychometric scores (SWPSs), and quality-adjusted LE (QALE). Materials and methods: To estimate survival outcomes, we retrospectively reviewed the data of 1576 patients treated for primary LHC between January 2010 and December 2018 and followed them until death or December 2020. We also prospectively collected QoL and functional data between October 2013 and November 2022 from 232 patients by administering the Taiwanese Chinese versions of the QoL Questionnaire Core 30, Head and Neck 35, and EQ-5D-3L. To estimate LE, we employed linear extrapolation of a logit-transformed curve. We calculated QALE and SWPSs by combining the QoL data with the LE results. Results: We estimated the LE of the patients with LHC to be 7.8 years and their loss of LE to be 15.7 years. The estimated QALE was 7.0 QALYs, with a loss of QALE of 16.5 QALYs. Lifetime impairment durations were estimated for cognitive (4.9 years), physical (4.2 years), emotional (3.4 years), social (3.4 years), and role functions (2.7 years). We estimated the durations of problems related to swallowing, speech, and teeth to be 6.2, 5.6, and 4.8 years, respectively. The patients were expected to be dependent on feeding tubes for 1.2 years. Conclusions: Patients with LHC experience significant reductions in both LE and QALE. SWPSs may constitute a valuable tool for obtaining subjective information regarding how LHC affects multifaceted QoL outcomes.

Should sub-millimeter margins be deemed positive in oral cavity squamous cell carcinoma?

BACKGROUND: While several studies have indicated that a margin status of < 1 mm should be classified as a positive margin in oral cavity squamous cell carcinoma (OCSCC), there is a lack of extensive cohort studies comparing the clinical outcomes between patients with positive margins and margins < 1 mm. METHODS: Between 2011 and 2020, we identified 18,416 Taiwanese OCSCC patients who underwent tumor resection and neck dissection. Of these, 311 had margins < 1 mm and 1013 had positive margins. To compare patients with margins < 1 mm and those with positive margins, a propensity score (PS)-matched analysis (n = 253 in each group) was conducted. RESULTS: The group with margins < 1 mm displayed a notably higher prevalence of several variables: 1) tongue subsite, 2) younger age, 3) smaller depth of invasion), 4) early tumor stage, and 5) treatment with surgery alone. Patients with margins < 1 mm demonstrated significantly better disease-specific survival (DSS) and overall survival (OS) rates compared to those with positive margins (74 % versus 53 %, 65 % versus 43 %, both p < 0.0001). Multivariable analysis further confirmed that positive margins were an independent predictor of worse 5-year DSS (hazard ratio [HR] = 1.38, p = 0.0103) and OS (HR = 1.28, p = 0.0222). In the PS-matched cohort, the 5-year outcomes for patients with margins < 1 mm compared to positive margins were as follows: DSS, 71 % versus 59 %, respectively (p = 0.0127) and OS, 60 % versus 48 %, respectively (p = 0.0398). CONCLUSIONS: OCSCC patients with a margin status < 1 mm exhibited distinct clinicopathological characteristics and a more favorable prognosis compared to those with positive resection margins.

Synergetic Modulation of Steric Hindrance and Excited State for Anti-Quenching and Fast Spin-Flip Multi-Resonance Thermally Activated Delayed Fluorophore.

Multi-resonance thermally activated delayed fluorescence (MR-TADF) materials hold great promise for advanced high-resolution organic light-emitting diode (OLED) displays. However, persistent challenges, such as severe aggregation-caused quenching (ACQ) and slow spin-flip, hinder their optimal performance. We propose a synergetic steric-hindrance and excited-state modulation strategy for MR-TADF emitters, which is demonstrated by two blue MR-TADF emitters, IDAD-BNCz and TIDAD-BNCz, bearing sterically demanding 8,8-diphenyl-8H-indolo[3,2,1-de]acridine (IDAD) and 3,6-di-tert-butyl-8,8-diphenyl-8H-indolo[3,2,1-de]acridine (TIDAD), respectively. These rigid and bulky IDAD/TIDAD moieties, with appropriate electron-donating capabilities, not only effectively mitigate ACQ, ensuring efficient luminescence across a broad range of dopant concentrations, but also induce high-lying charge-transfer excited states that facilitate triplet-to-singlet spin-flip without causing undesired emission redshift or spectral broadening. Consequently, implementation of a high doping level of IDAD-BNCz resulted in highly efficient narrowband electroluminescence, featuring a remarkable full-width at half-maximum of 34 nm and record-setting external quantum efficiencies of 34.3 % and 31.8 % at maximum and 100 cd m-2, respectively. The combined steric and electronic effects arising from the steric-hindered donor introduction offer a compelling molecular design strategy to overcome critical challenges in MR-TADF emitters.

Hybrid-Aligned Fibers of Electrospun Gelatin with Antibiotic and Polycaprolactone Composite Membranes as an In Vitro Drug Delivery System to Assess the Potential Repair Capacity of Damaged Cornea.

The cornea lacks the ability to repair itself and must rely on transplantation to repair damaged tissue. Therefore, creating alternative therapies using dressing membranes based on tissue engineering concepts to repair corneal damage before failure has become a major research goal. Themost outstanding features that are important in reconstructing a damaged cornea are the mechanical strength and transparency of the membrane, which are the most important standard considerations. In addition, preventing infection is an important issue, especially in corneal endothelial healing processes. The purpose of this study was to produce aligned fibers via electrospinning technology using gelatin (Gel) composite polycaprolactone (PCL) as an optimal transport and antibiotic release membrane. The aim of the composite membrane is to achieve good tenacity, transparency, antibacterial properties, and in vitro biocompatibility. Results showed that the Gel and PCL composite membranes with the same electrospinning flow rate had the best transparency. The Gel impregnated with gentamicin antibiotic in composite membranes subsequently exhibited transparency and enhanced mechanical properties provided by PCL and could sustainably release the antibiotic for 48 h, achieving good antibacterial effects without causing cytotoxicity. This newly developed membrane has the advantage of preventing epidermal tissue infection during clinical operations and is expected to be used in the reconstruction of damaged cornea in the future.

Is elective neck dissection justified in cT2N0M0 oral cavity cancer defined according to the AJCC eighth edition staging system?

BACKGROUND: The current NCCN guidelines recommend considering elective neck dissection (END) for early-stage oral cavity squamous cell carcinoma (OCSCC) with a depth of invasion (DOI) exceeding 3 mm. However, this DOI threshold, determined by evaluating the occult lymph node metastatic rate, lacks robust supporting evidence regarding its impact on patient outcomes. In this nationwide study, we sought to explore the specific indications for END in patients diagnosed with OCSCC at stage cT2N0M0, as defined by the AJCC Eighth Edition staging criteria. METHODS: We examined 4723 patients with cT2N0M0 OCSCC, of which 3744 underwent END and 979 were monitored through neck observation (NO). RESULTS: Patients who underwent END had better 5-year outcomes compared to those in the NO group. The END group had higher rates of neck control (95% vs. 84%, p < 0.0001), disease-specific survival (DSS; 87% vs. 84%, p = 0.0259), and overall survival (OS; 79% vs. 73%, p = 0.0002). Multivariable analysis identified NO, DOI ≥5.0 mm, and moderate-to-poor tumor differentiation as independent risk factors for 5-year neck control, DSS, and OS. Based on these prognostic variables, three distinct outcome subgroups were identified within the NO group. These included a low-risk subgroup (DOI <5 mm plus well-differentiated tumor), an intermediate-risk subgroup (DOI ≥5.0 mm or moderately differentiated tumor), and a high-risk subgroup (poorly differentiated tumor or DOI ≥5.0 mm plus moderately differentiated tumor). Notably, the 5-year survival outcomes (neck control/DSS/OS) for the low-risk subgroup within the NO group (97%/95%/85%, n = 251) were not inferior to those of the END group (95%/87%/79%). CONCLUSIONS: By implementing risk stratification within the NO group, we found that 26% (251/979) of low-risk patients achieved outcomes similar to those in the END group. Therefore, when making decisions regarding the implementation of END in patients with cT2N0M0 OCSCC, factors such as DOI and tumor differentiation should be taken into account.

Radiation-induced skin and heart toxicity in patients with breast cancer treated with adjuvant proton radiotherapy: a comparison with photon radiotherapy.

This study aimed to investigate the dose parameters and incidence of radiotherapy (RT)-associated toxicity in patients with left breast cancer (LBC) treated with proton-RT, compared with photon-RT. We collected data from 111 patients with LBC who received adjuvant RT in our department between August 2021 and March 2023. Among these patients, 24 underwent proton-RT and 87 underwent photon-RT. In addition to the dosimetric analysis for organs at risk (OARs), we measured NT-proBNP levels before and after RT. Our data showed that proton-RT improved dose conformity and reduced doses to the heart and lungs and was associated with a lower rate of increased NT-proBNP than did photon-RT. Regarding skin toxicity, the Dmax for 1 c.c. and 10 c.c. and the average dose to the skin-OAR had predictive roles in the risk of developing radiation-induced dermatitis. Although pencil beam proton-RT with skin optimization had a dose similar to that of skin-OAR compared with photon-RT, proton-RT still had a higher rate of radiation dermatitis (29%) than did photon RT (11%). Using mice 16 days after irradiation, we demonstrated that proton-RT induced a greater increase in interleukin 6 and transforming growth factor-ß1 levels than did photon-RT. Furthermore, topical steroid ointment reduced the inflammatory response and severity of dermatitis induced by RT. In conclusion, we suggest that proton-RT with skin optimization spares high doses to OARs with acceptable skin toxicity. Furthermore, prophylactic topical steroid treatment may decrease radiation dermatitis by alleviating proton-induced inflammatory responses in vivo.

Survival assessment of fractured porcelain-fused-to-metal crowns surface roughened by sandblasted and repaired by composite resin after in vitro thermal fatigue.

Background/purpose: Intraoral repair usually takes the convenience of the patient's daily life as the starting point, taking into account the bonding strength, operational feasibility, and safety. This study aimed to evaluate the survival of composite resin by simulating cavity fracture repair in porcelain-fused-to-metal (PFM) crowns and referring to the G.V. Black classification of caries as ceramic- and metal-site exposure. Materials and methods: Mechanical sandblast experimental and a nonsandblast control groups comprised 120 samples, and interfacial locking was enhanced through acid etching, bonding, and light-curing composite resin restoration. Classes of VI buccal (B), III mesial (M), and IV mesiobuccal (MB) types, were investigated. Load tests were performed on two sets, with one set at room temperature for 24 h and the other via thermal cycling at 5 °C/50 °C 720 times. Loading was gradually applied to the samples until a maximum of 450 N was reached. Results: Results showed that 24 h survival rates of B-, M - , and MB-repaired PFM crowns were 88%, 84%, and 88%, respectively. The repaired PFM survival rates for B, M, and MB were 52%, 44%, and 28%, respectively, after thermal cycling and loading tests. Multiple logistic regression and chi-square test (α = 0.05) showed that the regression results of factors affecting survival assessment were only significant between groups after thermal fatigue (P < 0.05). Survival rate of repairing metal-site in the MB model was significantly higher than that of ceramic-sites repairing in non-blasted samples. For the MB cavity model, sandblasting can significantly improve the survival rate of the repair of ceramic parts in the MB model (P < 0.05). Conclusion: Our results suggest that sandblasting can be further considered, especially for MB cavity fractures when ceramic-site restorations are required.

Reactive Oxygen Species-Mediated Mitophagy and Cell Apoptosis are Involved in the Toxicity of Aluminum Chloride Exposure in GC-2spd.

Aluminum chloride is an inorganic polymeric coagulant commonly found in daily life and various materials. Although male reproductive toxicity has been associated with AlCl3 exposure, the underlying mechanism remains unclear. This study aimed to examine the impact of AlCl3 exposure on mitophagy and mitochondrial apoptosis in testicular tissue and mouse spermatocytes. Reactive oxygen species (ROS) and ATP levels were measured in GC-2spd after AlCl3 exposure using a multifunctional enzyme labeler. The changes in mitochondrial membrane potential (MMP) and TUNEL were observed through confocal laser microscopy, and the expression of proteins associated with mitophagy and apoptosis was analyzed using Western blot. Our results demonstrated that AlCl3 exposure disrupted mitophagy and increased apoptosis-related protein expression in testicular tissues. In the in vitro experiments, AlCl3 exposure induced ROS production, suppressed cell viability and ATP production, and caused a decrease in MMP, leading to mitophagy and cell apoptosis in GC-2spd cells. Intervention with N-acetylcysteine (NAC) reduced ROS production and partially restored mitochondrial function, thereby reversing the resulting mitophagy and cell apoptosis. Our findings provide evidence that ROS-mediated mitophagy and cell apoptosis play a crucial role in the toxicity of AlCl3 exposure in GC-2spd. These results contribute to the understanding of male reproductive toxicity caused by AlCl3 exposure and offer a foundation for future research in this area.

Immediate implant placement with and without provisionalization: A comparison of a one-year longitudinal study.

Background/purpose: Immediate implant placement (IIP) with and without immediate provisionalization (Ipro) may yield satisfactory results in appropriate indications and treatment, especially in the esthetic zone. The aim of this study was to compare implant stability, marginal bone loss (MBL), survival rates, and patient satisfaction between IIP with Ipro and IIP without Ipro. Materials and methods: Seventy patients, each with a failed maxillary anterior tooth, were randomly assigned to IIP with Ipro (Group A: n = 35) or IIP without Ipro (Group B: n = 35). Implant stability quotient (ISQ) and standardized periapical radiographs were performed at surgery and at 3, 6, 9, and 12 months postoperatively to investigate implant stability and MBL, respectively. Survival was assessed 1 year after surgery. Patient satisfaction was evaluated with a visual analogue scale (VAS). Results: Primary ISQ and MBL were not significantly different between groups A and B immediately after surgery (P ＞ 0.05). Implant survival was 100% in both groups, and only one mechanical complication was observed. Patient satisfaction was good at definitive crown delivery and postoperatively 1-year in both groups. However, the immediate postoperative VAS score in Group A was significantly higher than that in Group B (P < 0.05). Conclusion: Group A revealed significantly higher secondary ISQ than Group B at postoperatively 3, 6, 9, and 12 months. There were no significant differences between groups A and B in terms of MBL and survival. Notably, patient satisfaction in Group A was significantly higher than in Group B immediately after surgery.

Implant stability and marginal bone level changes: A 2-year prospective pilot study.

Background/purpose: Implant stability is crucial for successful osseointegration. Marginal bone level is considered an important indicator of long-term implant success and stability. The purposes of this study were to investigate 1) the effect of age, gender, bone density, implant length, and implant diameter on insertion torque (IT), primary implant stability quotient (ISQ), and secondary ISQ, 2) the impact of age, gender, bone density, implant length, implant diameter, IT, and ISQ on marginal bone loss (MBL). Materials and methods: Ninety patients who needed implant therapy were enrolled and overall 156 implants were installed to support single crowns. IT and ISQ were recorded for all implants during surgery and ISQ measurements were performed at follow-up visits. Age, gender, bone density, implant length and diameter were also registered. Radiographic evaluation of MBL was performed postoperative immediate (baseline), 3, 6, 9, 12, 18, and 24 months using digital periapical radiographs. Results: Age had little effect on IT and primary ISQ (P > 0.05). Generally, males had higher IT and primary ISQ, but no significant differences between genders were detected. Bone density showed significant effects on IT and primary ISQ. Correlation analysis revealed high positive correlations between IT/bone density and primary ISQ/implant diameter. Significant impacts of bone density and IT on MBL were found. Conclusion: Implant diameter had a more profound impact than length on IT/primary ISQ. Bone density played a considerable role in IT/primary ISQ determination. Bone density and IT had more impacts than primary ISQ on MBL.

Postoperative radiotherapy alone is as effective as postoperative chemoradiotherapy in patients with pT4aN0 gingival cancer with negative surgical margins.

Background and purpose: This study compared the survival outcomes following postoperative chemoradiotherapy (CCRT) and postoperative radiotherapy (RT) alone for patients with gingival cancer with negative surgical margins and only bone invasion. Materials and methods: Of the 2579 gingival cancer cases reviewed from 2002 to 2018, 156 were enrolled in the study (CCRT: 63 patients; RT: 93 patients). The primary endpoints were the impact of adjuvant treatment (RT vs. CCRT) on overall survival (OS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS). Subgroup analyses were conducted based on surgical margins (<5 mm vs. ≥ 5 mm) and different adjuvant treatments (RT vs. CCRT). Results: Median follow-up time, age, and invasion depth were 88.5 months, 57 years, and 14 mm, respectively. More patients undergoing adjuvant CCRT had surgical margins < 5 mm (47.6% vs. 21.5%, p < 0.01) than those undergoing RT. No significant difference was observed in the 5-year OS, LRRFS, and DMFS of patients undergoing adjuvant RT and CCRT. Although adjuvant RT alone and CCRT provided similar local control for patients with surgical margins ≥ 5 mm, worse LRRFS trends were observed in patients with surgical margins < 5 mm (hazards ratio, 6.15, 95% confidence interval 0.92-41.13, p = 0.06). Conclusion: Postoperative RT alone may be effective for patients with gingival cancer with negative surgical margins (≥5 mm) and only bone invasion, while postoperative CCRT may result in better LRRFS than RT alone for patients with surgical margins < 5 mm.

The relationship of nutritional status with anticancer immunity and its prognostic value for head and neck cancer.

Malnutrition has been reported to be associated with reduced survival and deficient anticancer immunity, and undernourishment is a frequent comorbidity in head and neck cancer (HNC) patients. In this study, we evaluated the relationship between nutritional status and immunologic factors, and its prognostic value for HNC. We retrospectively reviewed 212 HNC patients who had undergone a nutrition evaluation based on the Patient-Generated Subjective Global Assessment (PG-SGA) and curative radiotherapy (RT). The role of nutritional status in the prognosis of HNC and its correlation with anticancer immune response was assessed in HNC patients, and in the 4-nitroquinoline 1-oxide (4NQO)-induced tongue tumor animal model. Our data revealed that malnutrition (high PG-SGA scores) was significantly associated with more advanced disease, lower body mass index, lower RT completion rates, and reduced survival. Patients in the group with high PG-SGA scores had a higher neutrophil-to-lymphocyte ratio, higher proportion of myeloid-derived suppressor cells (MDSCs), and elevated IL-6 levels in the peripheral circulation. Patients with increased PG-SGA scores following treatment were more likely to developing locoregional failure. In the 4NQO-induced tumor model, nutritional supplementation decreased the rate of invasive tumor formation and attenuated the immune-suppressive microenvironment. Following ectopic tumor implantation in an immunocompetent host, nutrition supplements decreased tumor growth in association with attenuated MDSC recruitment and lower IL-6 expression. In conclusion, malnutrition by PG-SGA was associated with poor prognosis in HNC patients. Based on the data of HNC patients and the 4NQO-tumor model, adequate nutritional supplementation might improve the prognosis associated with augmented anticancer immunity.

Synergistic effect of drug/antibiotic-impregnated micro/nanohybrid mesoporous bioactive glass/calcium phosphate composite bone cement on antibacterial and osteoconductive activities.

Calcium phosphate bone cements (CPC) can be used in minimally invasive surgery because of their injectability, and they can also be used to repair small and irregular bone defects. This study aimed to release the antibiotic gentamicin sulfate (Genta) to reduce tissue inflammation and prevent infection in the early stages of bone recovery. Subsequently, the sustained release of the bone-promoting drug ferulic acid (FA) mimicked the response of osteoprogenitor D1 cells interaction, thereby accelerating the healing process of the overall bone repair. Accordingly, the different particle properties of micro-nano hybrid mesoporous bioactive glass (MBG), namely, micro-sized MBG (mMBG) and nano-sized MBG (nMBG), were explored separately to generate different dose releases in MBG/CPC composite bone cement. Results show that nMBG had better sustained-release ability than mMBG when impregnated with the same dose. When 10 wt% of mMBG hybrid nMBG and composite CPC were used, the amount of MBG slightly shortened the working/setting time and lowered the strength but did not hinder the biocompatibility, injectability, anti-disintegration, and phase transformation of the composite bone cement. Furthermore, compared with 2.5wt%Genta@mMBG/7.5 wt% FA@nMBG/CPC, 5wt.%Genta@mMBG/5wt.%FA@nMBG/CPC exhibited better antibacterial activity, better compressive strength, stronger mineralization of osteoprogenitor cell, and similar 14-day slow-release trend of FA. The MBG/CPC composite bone cement developed can be used in clinical surgery to achieve the synergistic sustained release of antibacterial and osteoconductive activities.

Development and In Vitro Analysis of Layer-by-Layer Assembled Membranes for Potential Wound Dressing: Electrospun Curcumin/Gelatin as Middle Layer and Gentamicin/Polyvinyl Alcohol as Outer Layers.

Nanofibrous membranes made of hydrogels have high specific surface areas and are suitable as drug carriers. Multilayer membranes fabricated by continuous electrospinning could delay drug release by increasing diffusion pathways, which is beneficial for long-term wound care. In this experiment, polyvinyl alcohol (PVA) and gelatin were used as membrane substrates, and a sandwich PVA/gelatin/PVA structure of layer-by-layer membranes was prepared by electrospinning under different drug loading concentrations and spinning times. The outer layers on both sides were citric-acid-crosslinked PVA membranes loaded with gentamicin as an electrospinning solution, and the middle layer was a curcumin-loaded gelatin membrane for the study of release behavior, antibacterial activity, and biocompatibility. According to the in vitro release results, the multilayer membrane could release curcumin slowly; the release amount was about 55% less than that of the single layer within 4 days. Most of the prepared membranes showed no significant degradation during immersion, and the phosphonate-buffered saline absorption rate of the multilayer membrane was about five to six times its weight. The results of the antibacterial test showed that the multilayer membrane loaded with gentamicin had a good inhibitory effect on Staphylococcus aureus and Escherichia coli. In addition, the layer-by-layer assembled membrane was non-cytotoxic but detrimental to cell attachment at all gentamicin-carrying concentrations. This feature could be used as a wound dressing to reduce secondary damage to the wound when changing the dressing. This multilayer wound dressing could be applied to wounds in the future to reduce the risk of bacterial infection and help wounds heal.

Enhanced Cell Osteogenic Differentiation in Alendronate Acid and Flufenamic Acid Drug-Impregnated Nanoparticles of Mesoporous Bioactive Glass Composite Calcium Phosphate Bone Cement In Vitro.

This study aims to compare the anti-osteoporotic drugs alendronic acid (ALN) and flufenamic acid (FA) alone impregnate into nanoparticles of mesoporous bioactive glass (nMBG), which further composites calcium phosphate cement (CPC) and investigates their in vitro performance. The drug release, physicochemical properties, and biocompatibility of nMBG@CPC composite bone cement are tested, and the effect of the composites on improving the proliferation and differentiation efficiency of mouse precursor osteoblasts (D1 cells) is also investigated. Drug release shows that FA impregnates nMBG@CPC composite, a large amount of FA is released rapidly within 8 h, gradually reaching a stable release within 12 h, followed by a slow and sustained release within 14 days, and then reaches a plateau within 21 days. The release phenomenon confirms that the drug-impregnated nBMG@CPC composite bone cement effectively achieves slow drug delivery. The working time and setting time of each composite are within 4-10 min and 10-20 min, respectively, meeting the operational requirements of clinical applications. The addition of nMBG nanoparticles in the CPC matrix did not prevent the aggregation phenomenon under microstructural observation, thus resulting in a decrease in the strength of the nMBG@CPC composite. However, after 24 h of immersed reaction, the strength of each 5 wt.% nMBG impregnated with different concentrations of FA and ALN is still greater than 30 MPa, which is higher than the general trabecular bone strength. The drug-impregnated nMBG@CPC composites did not hinder the product formation and exhibit biocompatibility. Based on the proliferation and mineralization of D1 cells, the combination of nMBG with abundant FA and ALN in CPC is not conducive to the proliferation of D1 cells. However, when D1 cells are contact cultured for 21 days, alkaline phosphatase (ALP) enzyme activity shows higher ALP secretion from drug-impregnated nMBG@CPC composites than drug-free composites. Accordingly, this study confirms that nMBG can effectively impregnate the anti-osteoporosis drugs FA and ALN, and enhance the mineralization ability of osteoblasts. Furthermore, drug-impregnated nMBG applications can be used alone or in combination with CPC as a new option for osteoporotic bone-filling surgery.

Effect of Citric Acid on Swelling Resistance and Physicochemical Properties of Post-Crosslinked Electrospun Polyvinyl Alcohol Fibrous Membrane.

A series of electrospun polyvinyl alcohol (PVA) fiber membranes were crosslinked with citric acid (CA) at concentrations of 10, 20, and 30 wt.% (designated as CA10, CA20, and CA30). The effects of CA on the chemical structure, mechanical strength, swelling resistance, and cytotoxicity of the crosslinked PVA fibrous membranes were investigated. Infrared spectroscopy indicated the enhanced esterification of carboxyl and hydroxyl groups between CA and PVA. The modulus and strength of the electrospun PVA membrane increased due to the crosslinking between CA and PVA. The crosslinking of the PVA fiber matrix with CA increased the PVA binding point, thereby increasing the swelling resistance and modulus; however, the concentration of CA used was limited. Results showed that the water absorption of the PVA membranes decreased from 6.58 ± 0.04 g/g for CA10 to 3.56 ± 3.33 g/g for CA20 and 2.85 ± 0.40 g/g for CA30 with increasing CA. The water absorption remained unchanged after the membrane was soaked for a period of time, so no significant difference was found in the water absorption capacity of the same group after immersion from 1 h to 3 d. The tensile strength increased from 20.52 MPa of CA10 to 22.09 MPa of CA20. With an increased amount of CA used for crosslinking, the tensile strength and modulus of CA30 decreased to 11.48 and 13.94 MPa, respectively. Our study also showed that CA was not toxic to L929 cell viability when used for fiber crosslinking at less than 20 wt.% PVA, meaning it may be a good candidate as a support layer for guided tissue engineering.

IL-23/IL-17 immune axis mediates the imiquimod-induced psoriatic inflammation by activating ACT1/TRAF6/TAK1/NF-κB pathway in macrophages and keratinocytes.

The interleukin-23 (IL-23)/IL-17 immune axis has been linked to the pathology of psoriasis, but how this axis contributes to skin inflammation in this disease remains unclear. We measured inflammatory cytokines associated with the IL-23/IL-17 immune axis in the serum of patients with psoriasis using enzyme-linked immunosorbent assays. Psoriasis was induced in male C57BL/6J mice using imiquimod (IMQ) cream, and animals received intraperitoneal injections of recombinant mouse anti-IL-23A or anti-IL-17A antibodies for 7 days. The potential effects of the IL-23/IL-17 immune axis on skin inflammation were assessed based on pathology scoring, hematoxylin-eosin staining of skin samples, and quantitation of inflammatory cytokines. Western blotting was used to evaluate levels of the following factors in skin: ACT1, TRAF6, TAK1, NF-κB, and pNF-κB. The serum of psoriasis patients showed elevated levels of several cytokines involved in the IL-23/IL-17 immune axis: IL-2, IL-4, IL-8, IL-12, IL-17, IL-22, IL-23, and interferon-γ. Levels of IL-23p19 and IL-17 were increased in serum and skin of IMQ-treated mice, while ACT1, TRAF6, TAK1, NF-κB, and pNF-κB were upregulated in the skin. A large proportion of NF-κB p65 localized in nucleus of involucrin+ cells in the epidermis and in F4/80+ cells of the dermis of psoriatic lesional skin. Treating these animals with anti-IL-23 or anti-IL-17 antibodies improved pathological score and immune imbalance, mitigated skin inflammation and downregulated ACT1, TRAF6, TAK1, NF-κB, and pNF-κB in skin. Our results suggest that skin inflammation mediated by the IL-23/IL-17 immune axis in psoriasis involves activation of the ACT1/TRAF6/TAK1/NF-κB pathway in keratinocytes and macrophage.

Investigation on the effect of recasting palladium-silver alloy by argon arc vacuum pressure casting process.

Background/purpose: Palladium-silver (Pd-Ag) alloys are important as an alternative to gold-based alloys. The purpose of this study was to investigate the effect of an argon-arc vacuum pressure casting process on the recasting of the Pd-Ag alloy. Materials and methods: The recasting Pd-Ag alloys were compared with conventional horizontal centrifugal (HC) casting to an argon (Ar)-arc vacuum pressure (Ar-arc/VP) casting. The first-generation castings were made from a Pd-Ag alloy purchased from a supplier. Next-generation castings were made from 50 wt% Pd-Ag alloy before casting and 50 wt% from previous castings. This sequence was repeated over three generations to form the 2nd, 3rd and 4th recasting ingots. The ingots were then measured for marginal accuracy, interfacial oxidation, hardness and phase identification. Results: The recasting success rate of recastibility reached 100%. Compared with the HC group, the Ar-arc/VP group had better edge precision, smaller oxide layer thickness and lower hardness. The comparison of X-ray diffraction intensity showed that the relative intensities of Pd and Ag in the first, second and third generations recasting of the Ar-arc/VP group were significantly higher than those of the HC group. Phase analysis showed that the trace elements of indium and tin contents in the Pd-Ag recasting ingots of the Ar-arc/VP group were higher than those of the HC group. Conclusion: The results showed that the casting process used for recasting affected the quality of the Pd-Ag alloy. Therefore, Ar-arc/VP casting process could improve the effect of Pd-Ag recasting and maintain the alloy properties in comparison with HC casting.

Preliminary comparison of the remineralization and desensitization effects of a novel mineralized ion-releasing toothpaste and commercially available competitive products.

Background/purpose: Toothpaste plays an important role in brushing teeth to maintain oral hygiene and health. The purpose of this study was to develop a new toothpaste containing surface nanocrystal-rich dicalcium phosphate anhydrous (DCPA) powder and to investigate its effect on tooth samples. Materials and methods: The innovative toothpaste (REALCaP®/Group R) was compared with two commercial toothpastes (BioRepair®/Group B and Sensodyne®/Group S). Brushing cycle tests were performed on bovine tooth slices coated with individual toothpaste and a control group without toothpaste (Group C). Microhardness, roughness, surface structure observation, and X-ray diffraction (XRD) were performed on cycle days 4, 7, and 14 to analyze the impact of the toothpastes on tooth samples. Reults: Microhardness in the Group R was higher than that of the other groups regardless of the cycle days. Roughness in the Group R increased on days 4 and 7 but decreased on day 14. Roughness in the groups S and B increased with days. Microstructural observation revealed that most exposed dentinal tubules had been sealed in the Group R on day 14. Overlay thickness in the Group R was significantly higher than that in the groups S and B on days 4, 7, and 14. XRD analysis showed no hydroxyapatite (HA) peak in the Group S. The HA peak in the Group R was higher than that in the Group B on day 14. Conclusion: The innovative toothpaste has better properties than the commercially available products in terms of microhardness, roughness, and effectiveness in sealing dentinal tubules.