Reversed-engineered human alveolar lung-on-a-chip model.

Here, we present a physiologically relevant model of the human pulmonary alveoli. This alveolar lung-on-a-chip platform is composed of a three-dimensional porous hydrogel made of gelatin methacryloyl with an inverse opal structure, bonded to a compartmentalized polydimethylsiloxane chip. The inverse opal hydrogel structure features well-defined, interconnected pores with high similarity to human alveolar sacs. By populating the sacs with primary human alveolar epithelial cells, functional epithelial monolayers are readily formed. Cyclic strain is integrated into the device to allow biomimetic breathing events of the alveolar lung, which, in addition, makes it possible to investigate pathological effects such as those incurred by cigarette smoking and severe acute respiratory syndrome coronavirus 2 pseudoviral infection. Our study demonstrates a unique method for reconstitution of the functional human pulmonary alveoli in vitro, which is anticipated to pave the way for investigating relevant physiological and pathological events in the human distal lung.

OsPEX1, an extensin-like protein, negatively regulates root growth in a gibberellin-mediated manner in rice.

Leucine-rich repeat extensins (LRXs) are required for plant growth and development through affecting cell growth and cell wall formation. LRX gene family can be classified into two categories: predominantly vegetative-expressed LRX and reproductive-expressed PEX. In contrast to the tissue specificity of Arabidopsis PEX genes in reproductive organs, rice OsPEX1 is also highly expressed in roots in addition to reproductive tissue. However, whether and how OsPEX1 affects root growth is unclear. Here, we found that overexpression of OsPEX1 retarded root growth by reducing cell elongation likely caused by an increase of lignin deposition, whereas knockdown of OsPEX1 had an opposite effect on root growth, indicating that OsPEX1 negatively regulated root growth in rice. Further investigation uncovered the existence of a feedback loop between OsPEX1 expression level and GA biosynthesis for proper root growth. This was supported by the facts that exogenous GA3 application downregulated transcript levels of OsPEX1 and lignin-related genes and rescued the root developmental defects of the OsPEX1 overexpression mutant, whereas OsPEX1 overexpression reduced GA level and the expression of GA biosynthesis genes. Moreover, OsPEX1 and GA showed antagonistic action on the lignin biosynthesis in root. OsPEX1 overexpression upregulated transcript levels of lignin-related genes, whereas exogenous GA3 application downregulated their expression. Taken together, this study reveals a possible molecular pathway of OsPEX1mediated regulation of root growth through coordinate modulation of lignin deposition via a negative feedback regulation between OsPEX1 expression and GA biosynthesis.

A novel polymer enabled by polymerized small molecule strategy for tumor photothermal and photodynamic therapy.

Photothermal therapy (PTT) and photodynamic therapy (PDT) are effective method for tumor treatment. However, the limited variety and quantity of photothermal agents (PTAs) and photosensitizer (PSs) are still major challenges. Moreover, the cell apoptosis mechanism induced by PDT and PTT is still elusive. A fused-ring small molecule acceptor-donor acceptor' donor-acceptor (A-DA'D-A) type of Y5 (Scheme 1) has a narrow band-gap and strong light absorption. Herein, we used Y5 to polymerize with thiophene unit to obtain polymer PYT based on polymerized small molecule strategy, and PYT nanoparticles (PYT NPs) was prepared via one-step nanoprecipitation strategy with DSPE-PEG2000. PYT NPs had excellent biocompatibility, good photostability, high photothermal conversion efficiency (67%) and reactive oxygen species (ROS) production capacity under 808 nm laser irradiation (PYT NPs + NIR). In vitro and in vivo experiments revealed that PYT NPs + NIR had the ability to completely ablate tumor cells. It was demonstrated that cell apoptosis induced by PYT NPs + NIR was closely related to mitochondrial damage. This study provides valuable guidance for constructing high-performance organic PTAs and PSs for tumor treatment. Scheme 1 PYT enabled by polymerized small molecule strategy for tumor photothermal and photodynamic therapy.

A pilot investigation of condylar position and asymmetry in patients with unilateral posterior scissors-bite malocclusion based on three-dimensional reconstructive imaging technique.

OBJECTIVE: Unilateral posterior scissors-bite (uPSB) malocclusion is common clinically. This study aimed to investigate the condylar morphological alterations and condyle-fossa relationship in patients with uPSB, through cone beam computed tomography (CBCT) and three-dimensional reconstructive imaging technique. METHODS: A retrospective study was designed to comparatively analyze 95 patients with uPSB between July 2016 and December 2021. They were divided into three subgroups: 12 to 20, 21 to 30, and ≥ 31 years, according the age distribution. The morphological parameters regarding condyle, fossa, and joint space after three-dimensional reconstruction were measured and analyzed by a series of digital software. SPSS 26.0 software package was performed for statistical analysis on data sets, using paired t-test, one-way analysis of variance, Wilcoxon signed-rank sun test, Kruskal-Wallis H test, and Bonferroni correction. RESULTS: The condylar volume (CV) of scissors-bite side was greater than that of the non-scissors-bite side (CV A = 1740.68 ± 559.80 mm3 > CV N = 1662.25 ± 524.88 mm3, P = 0.027). So was the condylar superficial area (CSA) (CSA A = 818.71 ± 186.82 mm2 > CSA N = 792.63 ± 173.44 mm2, P = 0.030), and the superior joint space (SJS) [SJS A = 2.46 (1.61, 3.68) mm) > SJS N = 2.01 (1.55, 2.87) mm), P = 0.018], and the anterior joint space (AJS) (AJS A = 3.94 ± 1.46 mm > AJS N = 3.57 ± 1.30 mm, P = 0.017). The constituent ratios of the different parts of the bilateral condyles were 23% on the posterior slope, 21% on the top, 20% on the anterior slope, 19% on the lateral slope and 17% on the medial slope, respectively. CONCLUSION: Due to long-term abnormal occlusion of uPSB, the pathological bite force in temporomandibular joint would cause changes in the shape of the condyle. Among them, CV, CSA, SJS and AJS had significant changes in the scissors-bite status, which has the greatest damage to the posterior slope of the condyloid process.

A Diffused Mini-Sniffing Sensor for Monitoring SO2 Emissions Compliance of Navigating Ships.

The ship exhaust sniffing unmanned aerial vehicle (UAV) system can be applied to monitor vessel emissions in emission control areas (ECAs) to improve the efficiency of maritime law enforcement and reduce ship pollution. To solve the problems of large size, heavy weight and high cost of ship exhaust sniffing sensors, in this paper, a unique diffused mini-sniffing sensor was designed, which provides a low-cost, lightweight, and highly adaptable solution for ship exhaust sniffing UAV. To verify the measurement accuracy of the system, a large number of on-site tests were performed based in the mouth of the Yangtze River, and some cases of violation of the fuel sulfur content (FSC) were verified and punished. Maritime law enforcement officers boarded the ship to take oil samples from eight suspected ships and sent them to the laboratory for testing. The results showed that the FSCs of the eight ships in chemical inspection were all greater than the regulatory limit 0.5% (m/m) of the International Maritime Organization (IMO). The system enables authorities to monitor emissions using rotary UAVs equipped with diffused mini-sniffing sensors to measure the FSC of navigating ships, which couple hardware and operational software with a dedicated lab service to produce highly reliable measurement results. The system offers an effective tool for screening vessel compliance.

Influence of bone density on the accuracy of artificial intelligence-guided implant surgery: An in vitro study.

STATEMENT OF PROBLEM: Artificial intelligence (AI) has been found to be applicable in medical tests and diagnostics. However, studies on the application of AI technology in oral implantology are lacking. In addition, whether bone density affects the accuracy of guided implant surgery has not been determined. PURPOSE: The purpose of this in vitro study was to determine the clinical reliability of an AI-assisted implant planning software program with an in vitro model. An additional goal was to determine the effect of bone density on the accuracy of static computer-assisted implant surgery (CAIS). MATERIAL AND METHODS: Ten participants with missing mandibular left first molars were selected for analysis, and surgical fully guided templates were designed by using an AI implant planning software program. Jaw models were produced in 3 filling rate groups (group L: 25%; group M: 40%; group H: 55%, higher filling rate with representatives of the denser simulated bone density) by 3-dimensional (3D) printing. The preoperative and postoperative positions of the implants were compared by measuring the value of deviation through oral scanning. The mean 3D shoulder and apical and angular deviations were calculated for each group. The data were analyzed using 1-way ANOVA (α=.05 corrected for multiple testing by using Bonferroni-Holm adjustment). RESULTS: The mean ±standard deviation 3D shoulder and apical and angular deviations were 0.80 ±0.32 mm, 1.43 ±0.47 mm, and 3.68 ±1.30 degrees. These values were lower than the clinical safety distance of the fully guided implant template. A significantly lower mean 3D apical deviation (1.12 ±0.33 mm, P=.023) and angular deviation (2.81 ±1.11 degrees, P=.018) were observed in group L than in group H (1.68 ±0.37 mm, 4.32 ±0.99 degrees). However, no significant differences were found among the 3 groups in 3D deviation at the shoulder (P>.05). CONCLUSIONS: AI implant planning software program could design the ideal implant position through self-learning. The accuracy of the AI-assisted designed implant template in this study indicated its clinical reliability. Higher bone density led to increased implant deviations.

Generation of Cost-Effective Paper-Based Tissue Models through Matrix-Assisted Sacrificial 3D Printing.

Due to the combined advantages of cellulose and nanoscale (diameter 20-60 nm), bacterial cellulose possesses a series of attractive features including its natural origin, moderate biosynthesis process, good biocompatibility, and cost-effectiveness. Moreover, bacterial cellulose nanofibers can be conveniently processed into three-dimensional (3D) intertwined structures and form stable paper devices after simple drying. These advantages make it suitable as the material for construction of organ-on-a-chip devices using matrix-assisted sacrificial 3D printing. We successfully fabricated various microchannel structures embedded in the bulk bacterial cellulose hydrogels and retained their integrity after the drying process. Interestingly, these paper-based devices containing hollow microchannels could be rehydrated and populated with relevant cells to form vascularized tissue models. As a proof-of-concept demonstration, we seeded human umbilical vein endothelial cells (HUVECs) into the microchannels to obtain the vasculature and inoculated the MCF-7 cells onto the surrounding matrix of the paper device to build a 3D paper-based vascularized breast tumor model. The results showed that the microchannels were perfusable, and both HUVECs and MCF-7 cells exhibited favorable proliferation behaviors. This study may provide a new strategy for constructing simple and low-cost in vitro tissue models, which may find potential applications in drug screening and personalized medicine.

Self-assembled nanoparticles of reduction-sensitive poly (lactic-co-glycolic acid)-conjugated chondroitin sulfate A for doxorubicin delivery: preparation, characterization and evaluation.

In this study, reduction-sensitive self-assembled polymer nanoparticles based on poly (lactic-co-glycolic acid) (PLGA) and chondroitin sulfate A (CSA) were developed and characterized. PLGA was conjugated with CSA via a disulfide linkage (PLGA-ss-CSA). The critical micelle concentration (CMC) of PLGA-ss-CSA conjugate is 3.5 µg/mL. The anticancer drug doxorubicin (DOX) was chosen as a model drug, and was effectively encapsulated into the nanoparticles (PLGA-ss-CSA/DOX) with high loading efficiency of 15.1%. The cumulative release of DOX from reduction-sensitive nanoparticles was only 34.8% over 96 h in phosphate buffered saline (PBS, pH 7.4). However, in the presence of 20 mM glutathione-containing PBS environment, DOX release was notably accelerated and almost complete from the reduction-sensitive nanoparticles up to 96 h. Moreover, efficient intracellular DOX release of PLGA-ss-CSA/DOX nanoparticles was confirmed by CLSM assay in A549 cells. In vitro cytotoxicity study showed that the half inhibitory concentrations of PLGA-ss-CSA/DOX nanoparticles and free DOX against A549 cells were 1.141 and 1.825 µg/mL, respectively. Therefore, PLGA-ss-CSA/DOX nanoparticles enhanced the cytotoxicity of DOX in vitro. These results suggested that PLGA-ss-CSA nanoparticles could be a promising carrier for drug delivery.

Esthetic Evaluation of Implant-Supported Single Crowns: The Implant Restoration Esthetic Index and Patient Perception.

PURPOSE: To test the validity and reliability of a newly developed Implant Restoration Esthetic Index (IREI) and to compare esthetic outcomes reported by patients and professionals. MATERIALS AND METHODS: Ten graduate students and 10 prosthodontists assessed esthetic outcomes of 27 single-tooth implants with the IREI. Six peri-implant soft tissue parameters were measured using visual analog scales: mesial papilla presence, distal papilla presence, gingival trigone, soft tissue curvature, alveolar process deficiency, and soft tissue color and texture, as well as the six crown parameters: crown contour, crown position, crown labial convexity, crown characterization, crown color and translucency, and abutment visibility. The validity was tested based on Pearson's correlation. The internal consistency reliability was analyzed by Cronbach's alpha. Interclass correlation coefficients (ICC) were calculated to express the test-retest reliability and the inter-rater reliability. The correlations between patient and professional evaluations were analyzed by Pearson's correlation. RESULTS: The IREI demonstrated significant correlation (p < 0.05) to the pink esthetic score and white esthetic score (PES/WES). The internal consistency reliability showed a Cronbach's Alpha of 0.830. The test-retest reliability was excellent in both the graduate student group and the prosthodontist group, with ICCs of 0.961 and 0.952, respectively (p < 0.05). The inter-rater reliability was acceptable, with ICCs of 0.649 and 0.667, respectively (p < 0.05). Low correlation coefficients were found between patient and professional evaluations. CONCLUSIONS: The results of this study indicated that the IREI was considered a valid and reliable index involving sufficient parameters for professional esthetic evaluation of single-tooth implant restorations. The patient-reported esthetic outcomes had poor or no significant correlation to professional-reported outcomes.

[Application and Safety Evaluation of DEHP in PVC Medical Devices].

DEHP is largely used in soft PVC products as the plasticizer, which is also widely applied in medical devices. Due to its potential and widespread toxicity and medical devices' specific use, the safety of DEHP's application in medical devices has received extensive attention. In this paper, a comprehensive review of the application and potential toxicity of DEHP in PVC medical devices is made on the basis of the research results all over the world. Besides, the safety evaluation in medical devices is discussed and some possible coping strategies are explored.

The combination of herbal medicine Weng-li-tong with Tolterodine may be better than Tolterodine alone in the treatment of overactive bladder in women: a randomized placebo-controlled prospective trial.

BACKGROUND: To assess the efficacy and safety of the herbal medicine, Weng-li-tong (WLT) as monotherapy or combined with tolterodine in women with overactive bladder (OAB). METHODS: A prospective, randomized, single-blind multi-center trial was performed which included 182 OAB patients treated with either placebo (n = 26), WLT (n = 52), tolterodine (n = 52) or WLT plus tolterodine (n = 52). The overactive bladder symptom score (OABSS) and micturition behavior were measured to evaluate treatment efficacy. RESULTS: In total, 146 patients [placebo (n = 23), WLT (n = 39), tolterodine (n = 41) and WLT plus tolterodine (n = 43)] completed 8 weeks of treatment. Compared to those treated with placebo, patients in three intervention groups showed significant improvements in the OABSS, voiding frequency, average voided volume and urgency incontinence. WLT had a slower onset than tolterodine or combination therapy in reducing urgency incontinence. Compared with tolterodine, WLT had a weaker effect in improving OABSS (P = 0.022) and daily voiding frequency (P = 0.034). The combination therapy had better efficacy than WLT or tolterodine alone in improving the OABSS, voiding frequency and voided volume. No significant differences in the changes in quality of life scores were observed among the three intervention groups. Residual urine increased significantly in tolterodine group (P = 0.004), but not in combination group. WLT resulted in fewer adverse effects than tolterodine such as dry mouth (P = 0.002), weak stream (P = 0.002) and less residual urine (P < 0.001). CONCLUSIONS: WLT could improve OAB symptoms in women, while it had slower onset and weaker efficacy but fewer adverse effects than tolterodine. The combination of WLT and tolterodine was more efficacious than tolterodine alone in improving OAB symptoms. TRIAL REGISTRATION: Chinese Clinical Trial Registry [ ChiCTR-IPR-14005626 ]. Date of registration: 7 December 2014.

[Open, multicenter, phase â £ clinical trial of Shenbei Guchang capsules in treatment of diarrhea type irritable bowel syndrome].

To evaluate the safety and effectiveness of Shenbei Guchang capsules in treatment of diarrhea type irritable bowel syndrome (yang deficiency of spleen and kidney) under widely used conditions, an open, multicenter, controlled, phase Ⅳ clinical trial was conducted in the drug clinical trial centers of 16 domestic hospitals. 2 123 patients from June 10, 2011 to November 29, 2012 were enrolled in the trial. Drug clinical trial was approved by Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital Ethics Committee before implementation. Before the start of trial, subjects were selected according to the research scheme and inclusion criteria, then they would step into the 14 d study after signing Informed Consent Form. All subjects were treated according to the research scheme, evaluated the conditions and filled in CFR sheet, to provide the evaluation data and information on safety and efficacy of Shenbei Guchang capsules. Shenbei Guchang capsules were used to treat diarrhea type irritable bowel syndrome in widely used conditions (2 123 cases), and 2 029 cases of them entered FAS set, cure+markedly effective in 1 921 cases, with a comprehensive curative effect rate of 94.68%; 2 010 cases of them entered PPS set, cure+markedly effective in 1 906 cases, with a comprehensive curative effect rate of 94.83%. The primary symptoms of IBS were abdominal pain and diarrhea. After treatment, both abdominal pain and diarrhea were improved, with significant differences (P<0.000 1). There were significant differences in traditional Chinese medicine symptom scores on both post-treatment day 7 and day 14 as compared with the conditions before treatment (P<0.000 1). 35 cases of adverse events occurred during the trial with an incidence of 1.65%, including 12 cases of drug-related adverse events (adverse reaction) with an incidence of 0.57%, mainly manifested as nausea, abdominal distension and dry mouth, most of which would be spontaneously relieved without any measures. No serious adverse events occurred. The commercially available Shenbei Guchang capsules are proved safe and effective for the treatment of diarrhea type irritable bowel syndrome (yang deficiency of spleen and kidney) under widely used conditions (2 123 cases), and can be continued for clinical promotion and application.

Water-soluble biopolymers calcium polymalate derived from fermentation broth of Aureobasidium pullulans markedly alleviates osteoporosis and fatigue.

Osteoporosis is a prevalent condition characterized by bone loss and decreased skeletal strength, resulting in an elevated risk of fractures. Calcium plays a crucial role in preventing and managing osteoporosis. However, traditional calcium supplements have limited bioavailability, poor solubility, and adverse effects. In this study, we isolated a natural soluble biopolymer, calcium polymalate (PMACa), from the fermentation broth of the fungus Aureobasidium pullulans, to investigate its potential as an anti-osteoporosis therapeutic agent. Characterization revealed that linear PMA-Ca chains juxtaposed to form a porous, rod-like state, in the presence of Ca2+. In vivo mouse models demonstrated that PMA-Ca significantly promoted the conversion of serum calcium into bone calcium, and stimulated bone growth and osteogenesis. Additionally, PMA-Ca alleviated exercise fatigue in mice by facilitating the removal of essential metabolites, such as serum lactate (BLA) and blood urea nitrogen (BUN), from their bloodstream. In vitro studies further showed that PMA-Ca strengthened osteoblast cell activity, proliferation, and mineralization. And PMA-Ca upregulated the expression of some genes involved in osteoblast differentiation, indicating a potential correlation between bone formation and PMACa. These findings indicate that soluble PMA-Ca has the potential to be a novel biopolymer-based calcium supplement with sustainable production sourced from the fermentation industry.

The exploration of a compound cone-beam CT contrast agent for diagnosis of human extracted cracked tooth.

Objectives: This study aims to investigate the use of sodium iodide (NaI), dimethyl sulfoxide (DMSO), ethyl alcohol, and ethyl acetate as cone-beam CT (CBCT) contrast agents for diagnosing cracked teeth. The optimal delay time for detecting the number of crack lines beyond the dentino-enamel junction (Nd), the number of cracks extending from the occlusal surface to the pulp cavity (Np), and the depth of the crack lines was explored. Methods: 14 human extracted cracked teeth were collected, 12 were used for enhanced scanning, and 2 were used for exploring the characteristic of crack lines. The teeth were scanned in 3 CBCT enhanced scanning (ES) modes: ES1 using meglumine diatrizoate (MD); ES2 using NaI and DMSO, ES3 using NaI, DMSO, ethyl alcohol and ethyl acetate. Three delay times (15mins, 30mins, and 60mins) were set for scanning. Nd, Np, and depth of crack lines were evaluated. Results: There were totally 24 crack lines on 12 cracked teeth. Nd was 10 in ES1 at 60mins, 24 in ES2 at 60mins and 24 in ES3 at 15mins. Np was 1 in ES1 at 60mins, 10 in ES2 at 60mins and 21 in ES3 at 60mins, and there were significantly different among them (p < 0.01). The average depth presented on ES3 was significantly deeper than ES1 and ES2 (p < 0.01). Conclusion: NaI, DMSO, ethyl alcohol and ethyl acetate show potential as contrast agents for enhanced CBCT scanning in diagnosis of cracked teeth and their depth in vivo. A delay time of 15 min is necessary to confirm the existence of crack lines, while a longer delay time is required to ascertain if these crack lines extend to the pulp cavity.

Engineering tubular bone using mesenchymal stem cell sheets and coral particles.

The development of bone tissue engineering has provided new solutions for bone defects. However, the cell-scaffold-based approaches currently in use have several limitations, including low cell seeding rates and poor bone formation capacity. In the present study, we developed a novel strategy to engineer bone grafts using mesenchymal stem cell sheets and coral particles. Rabbit bone marrow mesenchymal stem cells were continuously cultured to form a cell sheet with osteogenic potential and coral particles were integrated into the sheet. The composite sheet was then wrapped around a cylindrical mandrel to fabricate a tubular construct. The resultant tubular construct was cultured in a spinner-flask bioreactor and subsequently implanted into a subcutaneous pocket in a nude mouse for assessment of its histological characteristics, radiological density and mechanical property. A similar construct assembled from a cell sheet alone acted as a control. In vitro observations demonstrated that the composite construct maintained its tubular shape, and exhibited higher radiological density, compressive strength and greater extracellular matrix deposition than did the control construct. In vivo experiments further revealed that new bone formed ectopically on the composite constructs, so that the 8-week explants of the composite sheets displayed radiological density similar to that of native bone. These results indicate that the strategy of using a combination of a cell sheet and coral particles has great potential for bone tissue engineering and repairing bone defects.

Changes of dental anxiety, aesthetic perception and oral health-related quality of life related to influencing factors of patients' demographics after anterior implant treatment: a prospective study.

BACKGROUND: Accumulating evidence has revealed the effects of anterior implant procedures on dental anxiety (DA), aesthetic perception and oral health-related quality of life (OHRQoL). However, few reported the changes and influencing factors of the above outcomes before and after anterior implant treatment. This study was to evaluate the changes of DA, aesthetic perception and OHRQoL related to influencing factors of patients' demographics after anterior implant treatment. METHODS: Thirty-nine patients satisfying the inclusion criteria were prospectively recruited before surgery. The subjects completed the Modified Dental Anxiety Scale (MDAS), the Orofacial Esthetic Scale (OSE) and the Oral Health Impact Profile-14 (OHIP-14), before implant surgery and after definitive prosthesis placement. Mann-Whitney U test and Kruskal-Wallis test by Bonferroni correction were applied for the data analysis and the influencing factors evaluation (p < 0.05). RESULTS: Overall, 39 patients (mean age of 44.9 ± 12.0) completed the three scales. After anterior implant treatment, MDAS was not significantly changed (p > 0.05). The overall OSE (p < 0.001) and OHIP-14 (p < 0.05) were significantly improved. Females showed more improvement of overall OHIP score than males after anterior implant treatment (p < 0.05). CONCLUSIONS: Anterior implant procedures did not change the level of patient's DA, while aesthetic perception and OHRQoL were enhanced. Only gender difference of overall OHIP change was found in our study. Thus, more related influencing factors with larger sample and long-term effective follow-up are needed. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05424458. Registered 13 June 2022-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT05424458 .

Development of a predictive model for identifying previously undetected vertical root fractures.

This study aimed to develop a predictive model to screen for undetected vertical root fractures (VRFs) in root canal treated teeth. We included 95 root canal treated teeth with suspected VRFs; 77 for training and 18 for validation. Following clinical and cone-beam CT parameters were recorded: sex, tooth type, coronal restoration, time interval from completion of endodontic treatment to definitive diagnosis (TI), type of bone loss (BL), apical extent of root filling (AR) and the ratio of root filling diameter to the actual diameter in the coronal (1/3TA) and middle (2/3TA) root thirds. A predictive model p = 1/(1 - e-x ) was generated, where x = -7.433 + 1.977BL + 1.479 (2/3TA) + 1.102 AR; the sensitivity and specificity were 0.852 and 0.875 for training and 0.917 and 0.833 for validation. VRF teeth were more likely to have vertical bone loss and overfilled root canals. This model had a high diagnostic efficacy for VRFs.

Peptide-modified bioresponsive chondroitin sulfate micelles for targeted doxorubicin delivery in triple-negative breast cancer.

Triple-negative breast cancer is an offensive tumor that is highly challenging to cure. In this study, we developed novel polymeric nanoparticles that target dual receptors and respond to reducing conditions for chemotherapeutic drug release in the treatment of triple-negative breast cancer. Then we synthesized and characterized a targeted peptide-grafted chondroitin sulfate A-ss-deoxycholic acid (TCSSD) copolymer and prepare doxorubicin (DOX)-loaded TCSSD (TCSSD-D) micelles high-loading content. The bioresponsive drug release of TCSSD-D nanoparticles was demonstrated in a glutathione-containing phosphate buffer solution. We found that TCSSD-D effectively targeted CD44 and P-selectin receptors both in vitro and in vivo. TCSSD-D micelles were higher cytotoxicity and cellular uptake than unmodified DOX-containing micelles in MDA-MB-231 cells. Furthermore, TCSSD-D micelles showed the strongest suppression of tumor growth among three DOX-based formulations in triple-negative MDA-MB-231-bearing nude mice. These results suggest that amphiphilic TCSSD nanoparticles can serve as a targeted and intelligent delivery vehicle for triple-negative breast cancer therapy.

Establishment of Narrow Root Fracture Models Using Modified Temperature Cycling Method and Diagnosis Using Different Cone-Beam CT Units.

Aim: Using a modified thermal cycling method to establish narrow root fracture models and evaluate the diagnosis efficiency of them using four different cone-beam CT (CBCT) units. Methodology. Fifty-six intact teeth were selected, and the crowns of the teeth were embedded using general purpose acrylic resin. 50 root fracture models were established by soaking these teeth in liquid nitrogen and hot water cyclically; 6 teeth were used as the negative control. All the 56 teeth were scanned with the smallest voxel size of four different CBCT units (NewTom VGi, Planmeca Promax 3D Max, Kavo 3D eXam, and Soredex Scanora3D). 10 teeth were randomly selected, and the roots were sliced using slow-speed saw to obtain horizontal root sections. Scanning electron microscope (SEM) was used to measure the width of the fracture lines (FLs). The CBCT images were evaluated for the presence or absence of fracture lines. Accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for the diagnosis of FLs using the four CBCT units. Results: Fifty narrow root fracture models were successfully established, and 25 root sections with 45 FLs were acquired. The width of FLs was from 3.43 µm to 143 µm; 32.2% of the points had width under 25 µm, while only 9.6% of them had width over 75 µm. The accuracy was 0.41, 0.54, 0.41, and 0.30 for NewTom VGi, Planmeca Promax 3D Max, Kavo 3D eXam, and Soredex Scanora3D, respectively. Conclusions: The modified temperature cycling method is a simple and effective method to establish narrow root fracture models, and the diagnosis efficiency for these narrow fracture lines was quite poor using all the four different CBCT units.

DNAzyme-adsorbed polydopamine@MnO2 core-shell nanocomposites for enhanced photothermal therapy via the self-activated suppression of heat shock protein 70.

Photothermal therapy (PTT) is a promising tumor treatment modality, but its efficacy is strictly hindered by abnormally upregulated heat shock proteins (HSPs) in tumor cells under heat stress. Herein, we developed a flower-like MnO2-coated polydopamine (PDA@MnO2) core-shell nanoplatform with the surface adsorption of HSP70-silencing DNAzyme (DZ) for enhanced PPT. The PDA core acted as a robust photothermal agent, and also as a reductant to allow the surface growth of MnO2via an in situ reduction of KMnO4. The MnO2 shell enabled a rapid and efficient adsorption of DZ, and more importantly, acted as a metal reservoir to release Mn2+ in response to intracellular stimuli for the in situ activation of DZ, which addressed the key limitation of DZ for biological applications, i.e., metal-dependent activity. As a result, HSP70 was remarkably suppressed for improved PTT efficacy upon laser irradiation, which was explicitly demonstrated both in vitro and in vivo. Upon intravenous injection, the nanosystem could effectively accumulate in the tumor, and impose potent PTT for complete tumor elimination via inducing tumor cell apoptosis, but without any noticeable toxicity. This work provides a promising nanosystem for enhanced PTT via silencing resistance-related genes, and offers ideas for the design of self-activated gene therapy platforms using DZ.