Predicting prognosis and immunotherapy response in colorectal cancer by pericytes insights from single-cell RNA sequencing.

Immunotherapy has revolutionized the treatment of tumors, but there are still a large number of patients who do not benefit from immunotherapy. Pericytes play an important role in remodeling the immune microenvironment. However, how pericytes affect the prognosis and treatment resistance of tumors is still unknown. This study jointly analyzed single-cell RNA sequencing (scRNA-seq) data and bulk RNA sequencing data of multiple cancers to reveal pericyte function in the colorectal cancer microenvironment. Analyzing over 800 000 cells, it was found that colorectal cancer had more pericyte enrichment in tumor tissues than other cancers. We then combined the TCGA database with multiple public datasets and enrolled more than 1000 samples, finding that pericyte may be closely related to poor prognosis due to the higher epithelial-mesenchymal transition (EMT) and hypoxic characteristics. At the same time, patients with more pericytes have higher immune checkpoint molecule expressions and lower immune cell infiltration. Finally, the contributions of pericyte in poor treatment response have been demonstrated in multiple immunotherapy datasets (n = 453). All of these observations suggest that pericyte can be used as a potential biomarker to predict patient disease progression and immunotherapy response.

Nerve Growth Factor-Preconditioned Mesenchymal Stem Cell-Derived Exosome-Functionalized 3D-Printed Hierarchical Porous Scaffolds with Neuro-Promotive Properties for Enhancing Innervated Bone Regeneration.

The essential role of the neural network in enhancing bone regeneration has often been overlooked in biomaterial design, leading to delayed or compromised bone healing. Engineered mesenchymal stem cells (MSCs)-derived exosomes are becoming increasingly recognized as potent cell-free agents for manipulating cellular behavior and improving therapeutic effectiveness. Herein, MSCs are stimulated with nerve growth factor (NGF) to regulate exosomal cargoes to improve neuro-promotive potential and facilitate innervated bone regeneration. In vitro cell experiments showed that the NGF-stimulated MSCs-derived exosomes (N-Exos) obviously improved the cellular function and neurotrophic effects of the neural cells, and consequently, the osteogenic potential of the osteo-reparative cells. Bioinformatic analysis by miRNA sequencing and pathway enrichment revealed that the beneficial effects of N-Exos may partly be ascribed to the NGF-elicited multicomponent exosomal miRNAs and the subsequent regulation and activation of the MAPK and PI3K-Akt signaling pathways. On this basis, N-Exos were delivered on the micropores of the 3D-printed hierarchical porous scaffold to accomplish the sustained release profile and extended bioavailability. In a rat model with a distal femoral defect, the N-Exos-functionalized hierarchical porous scaffold significantly induced neurovascular structure formation and innervated bone regeneration. This study provided a feasible strategy to modulate the functional cargoes of MSCs-derived exosomes to acquire desirable neuro-promotive and osteogenic potential. Furthermore, the developed N-Exos-functionalized hierarchical porous scaffold may represent a promising neurovascular-promotive bone reparative scaffold for clinical translation.

The tumor immune microenvironment of nasopharyngeal carcinoma after gemcitabine plus cisplatin treatment.

Gemcitabine plus cisplatin (GP) chemotherapy is the standard of care for nasopharyngeal carcinoma (NPC). However, the mechanisms underpinning its clinical activity are unclear. Here, using single-cell RNA sequencing and T cell and B cell receptor sequencing of matched, treatment-naive and post-GP chemotherapy NPC samples (n = 15 pairs), we show that GP chemotherapy activated an innate-like B cell (ILB)-dominant antitumor immune response. DNA fragments induced by chemotherapy activated the STING type-I-interferon-dependent pathway to increase major histocompatibility complex class I expression in cancer cells, and simultaneously induced ILB via Toll-like receptor 9 signaling. ILB further expanded follicular helper and helper type 1 T cells via the ICOSL-ICOS axis and subsequently enhanced cytotoxic T cells in tertiary lymphoid organ-like structures after chemotherapy that were deficient for germinal centers. ILB frequency was positively associated with overall and disease-free survival in a phase 3 trial of patients with NPC receiving GP chemotherapy ( NCT01872962 , n = 139). It also served as a predictor for favorable outcomes in patients with NPC treated with GP and immunotherapy combined treatment (n = 380). Collectively, our study provides a high-resolution map of the tumor immune microenvironment after GP chemotherapy and uncovers a role for B cell-centered antitumor immunity. We also identify and validate ILB as a potential biomarker for GP-based treatment in NPC, which could improve patient management.

Immune response and homeostasis mechanism following administration of BBIBP-CorV SARS-CoV-2 inactivated vaccine.

The BBIBP-CorV severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inactivated vaccine has been authorized for emergency use and widely distributed. We used single-cell transcriptome sequencing to characterize the dynamics of immune responses to the BBIBP-CorV inactivated vaccine. In addition to the expected induction of humoral immunity, we found that the inactivated vaccine induced multiple, comprehensive immune responses, including significantly increased proportions of CD16+ monocytes and activation of monocyte antigen presentation pathways; T cell activation pathway upregulation in CD8+ T cells, along with increased activation of CD4+ T cells; significant enhancement of cell-cell communications between innate and adaptive immunity; and the induction of regulatory CD4+ T cells and co-inhibitory interactions to maintain immune homeostasis after vaccination. Additionally, comparative analysis revealed higher neutralizing antibody levels, distinct expansion of naive T cells, a shared increased proportion of regulatory CD4+ T cells, and upregulated expression of functional genes in booster dose recipients with a longer interval after the second vaccination. Our research will support a comprehensive understanding of the systemic immune responses elicited by the BBIBP-CorV inactivated vaccine, which will facilitate the formulation of better vaccination strategies and the design of new vaccines.

Interferon-dependent SLC14A1+ cancer-associated fibroblasts promote cancer stemness via WNT5A in bladder cancer.

Cancer-associated fibroblasts (CAFs) play a role in response to cancer treatment and patient prognosis. CAFs show phenotypic and functional heterogeneity and differ widely in tumors of different tissue origin. Here, we use single-cell RNA sequencing of bladder cancer (BC) patient samples and report a CAF subpopulation characterized by overexpression of the urea transporter SLC14A1. This population is induced by interferon signaling and confers stemness to BC cells via the WNT5A paracrine pathway. Activation of cGAS-STING signaling in tumor cells drives interferon production, thereby revealing a link between cGAS-STING signaling and SLC14A1+ CAF differentiation. Furthermore, the inhibition of SLC14A1+ CAF formation via targeting of STAT1 or STING sensitizes tumor cells to chemotherapy. More important, BC patients with high proportions of intratumoral SLC14A1+ CAFs show cancer stage-independent poor outcome and a worse response rate to neoadjuvant chemotherapy or immunotherapy.

Bleeding Outcomes After Dental Extraction in Patients Under Direct-Acting Oral Anticoagulants vs. Vitamin K Antagonists: A Systematic Review and Meta-Analysis.

Background: The current systematic review aimed to compare bleeding outcomes in dental extraction patients receiving uninterrupted Direct-acting oral anticoagulant (DOAC) or Vitamin K antagonists (VKAs) for various systemic diseases. Methods: PubMed, Embase, ScienceDirect, CENTRAL, and Google Scholar databases were searched for randomized controlled trials, controlled clinical trials, prospective and retrospective cohort studies, and case control studies, conducted on adult patients undergoing dental extraction under uninterrupted DOAC or VKAs therapy and reporting bleeding outcomes. The search was conducted up to March 31, 2021. We pooled data to calculate risk ratios (RR) with 95% confidence intervals (CI) in a random-effects model. Results: Eight studies comparing 539 patients on DOAC therapy and 574 patients on VKAs were included. Meta-analysis indicated a statistically significant lower bleeding risk in patients under DOAC therapy (RR 0.68 95% CI 0.49, 0.95 I2 = 0%). However, on sensitivity analysis, the results were statistically non-significant after exclusion of any of the included studies. On pooled analysis of limited number of studies, we found no statistically significant difference in the risk of bleeding between apixaban (RR 0.85 95% CI 0.45, 1.60 I2 = 0%), rivaroxaban (RR 0.95 95% CI 0.36, 2.48 I2 = 45%), dabigatran (RR 0.49 95% CI 0.19, 1.28 I2 = 5%), edoxaban (RR 0.41 95% CI 0.13, 1.27 I2 = 0%) and VKAs. Conclusion: The results of the first review comparing bleeding outcomes after dental extraction in patients on uninterrupted DOAC or VKA therapy indicates that patients on DOAC may have a reduced risk of hemorrhage. Current evidence is of very low-quality and should be interpreted with caution. Data on individual DOAC is scarce and at this point, the difference in the risk of bleeding between these drugs cannot be elucidated. Further studies with a large sample size shall supplement our conclusion.

Selenium-silicon (Se-Si) induced modulations in physio-biochemical responses, grain yield, quality, aroma formation and lodging in fragrant rice.

Fragrant rice is a high-valued quality rice type which is gaining much popularity over the globe due to its better cooking qualities and special aromatic characteristics. Selenium (Se) and silicon (Si) could improve the growth and yield of rice; however, the combine effects of Se and Si (Se-Si treatments) on rice grain quality, aroma and lodging in fragrant rice were rarely investigated. The pot and field experiments were conducted with two fragrant rice cultivars i.e., Xiangyaxiangzhan and Yuxiangyouzhan, grown under three Se levels i.e., 0, 120, and 240 mg kg-1 of soil (for pot experiment) and 0, 300, and 600 kg ha-1 (for field experiment) regarded as LSe, MSe and HSe, respectively and two Si levels i.e., 0 and 60 mg kg-1 of soil (for pot experiment) and 0 and 150 kg ha-1 (for field experiment) regarded as -Si and +Si, respectively. Results depicted that the Se-Si treatments regulated head rice yield, grain yield and yield related traits and the HSe+Si treatment sustainably improved the grain yield and head rice yield by regulating plant growth, antioxidant response and malondialdehyde (MDA) contents in fragrant rice. The Se-Si treatments also improved the grain 2AP contents owing to regulation in the proline, pyrroline-5-carboxylate (P5C) and γ-aminobutyric acid (GABA) contents. Besides, Se-Si treatments also regulated the grain quality attributes and influenced the plant Se contents. Moreover, the Si mitigated Se-induced lodging resulted from changes in the lodging parameters i.e., lodging index, fresh weight per tiller, pushing resistance force, plant height and bending moment. Overall, the Se and Si application improved the grain yield and regulated the dry weight accumulation, antioxidant attributes and quality attributes. Meanwhile, the Si application mitigated the negative effect of Se-induced lodging in fragrant rice.

Response of rice genotypes with differential nitrate reductase-dependent NO synthesis to melatonin under ZnO nanoparticles' (NPs) stress.

Nitrate reductase is a nitric oxide (NO) induced enzyme in plants, NO acts as a signaling molecule under ZnO NPs-induced stress whereas melatonin (N-acetyl-5-methoxytryptamine) could improve morpho-physiological attributes of plants under adverse conditions. In present study, seedlings of two rice genotypes differed regarding nitrate reductase activities i.e., transgenic 'NR' and wild type 'WT' were applied with two melatonin levels i.e., 0, 10 µΜ regarded as M0, M10, respectively and three levels of ZnO NPs i.e., 0, 50, 500 mg L-1 regarded as ZnO NPs0, ZnO NPs50 and ZnO NPs500, respectively. Results revealed that melatonin application substantially increased the dry biomass accumulation of both rice genotypes under all ZnO NPs levels. The root growth, mineral absorption as well as the antioxidant responses were also improved by melatonin application under ZnO NPs stress. The interactive effects of melatonin and genotype on plant growth, antioxidant responses and mineral contents i.e., Zn, Na, Fe and Mn were also found significant under different ZnO NPs stress. Furthermore, total plant dry weight was significantly correlated with the leaf dry weight, root volume, catalase (CAT) activity in leaves, Na accumulation in stem sheath and Fe accumulation in root under both M0 and M10 treatments. Moreover, the comparative transcriptome analysis identified key genes which were responsible for melatonin and NO-induced modulations in plant growth under ZnO NPs stress. Overall, melatonin could improve the morphological growth of the rice plants by modulating root-shoot characteristics, antioxidant activities and mineral uptake in root and shoot of rice.

Factors that Influence Direction Deviation in Freehand Implant Placement.

PURPOSE: This retrospective study investigates the accuracy of freehand implant placement and whether the factors of presence of an adjacent tooth, implant quadrant, number of missing teeth, and location of the implant site influence direction and angulation deviations. MATERIALS AND METHODS: According to specific inclusion and exclusion criteria, a total of 112 implants from 75 partially edentulous patients were recruited for this retrospective study. The implants were inserted using a freehand approach by one experienced clinician (right-handed). The full thickness flap was elevated to expose the alveolar bone in the implant surgery, and the implant crown consisted of an all-ceramic restoration retained by cement. The planned implant position was preoperatively determined using implant planning software. The postoperative implant position was determined by analyzing the alignment after optically scanning the dentition using a specifically designed registration model in Geomagic Studio software. The deviations between the planned and postoperative implant positions were then calculated. The outcomes included direction and angulation deviations between the planned and postoperative implant positions. All data were analyzed by ANOVA, Bonferroni correction, regression analysis, and one-sample t-tests conducted using SPSS. RESULTS: The 3D deviations between planned and postoperative implant positions were 1.22 ± 0.63 mm at the entrance point, 1.91 ± 1.17 mm at the apical point, and 7.93 ± 5.56° in angulation. The presence of adjacent teeth influenced deviations in the mesiodistal (F = 4.338, p = 0.006) and buccolingual directions (F = 3.017, p = 0.033) at the entrance point and mesiodistal angulation (F = 7.979, p < 0.001). The quadrant influenced deviation in the buccolingual direction at the apical point (F = 6.093, p = 0.001) and buccolingual angulation (F = 6.457, p < 0.001). The number of missing teeth had no effect on deviations of direction and angulation of implants. The location of the implant site affected the deviation in the buccolingual direction at the entrance point (F = 3.096, p = 0.049) and the mesiodistal direction at the apical point (F = 3.724, p = 0.027). CONCLUSION: The 3D accuracy of freehand-placed implants could be acceptable in clinical situations. The results showed that the presence of an adjacent tooth and the quadrant and the location of the implant site influenced the direction and angulation deviations of the implant position; however, the factor of number of missing teeth did not.

Accuracy of the evaluation of implant position using a completely digital registration method compared with a radiographic method.

STATEMENT OF PROBLEM: Conventional radiographic methods are widely used to evaluate the clinical accuracy of implant position. However, such methods require a second computerized tomography (CT) scan and manual registration between presurgical and postsurgical CT data. The alignment errors cannot be calculated. PURPOSE: The purpose of this clinical study was to introduce a completely digital registration method to evaluate the clinical accuracy of implant position. The digital registration method was then compared with the radiographic method in evaluating accuracy. Some of the alignment errors produced in the digital registration procedures were recorded. MATERIAL AND METHODS: A total of 32 implants from 19 patients with sufficient bone volume were enrolled in the study, and all implant surgeries were conducted by one experienced practitioner. Before the surgery, a cone beam computerized tomography (CBCT) scan was made for each patient along with a diagnostic impression to design the ideal implant position using the Simplant software. After the surgery, the postsurgical implant position was determined using an optical scan of the dentition cast and a series of custom registration models (the digital registration method). A simulated cylinder was designed using the Geomagic Studio software to represent the implant, and the deviation of the ideal and postsurgical implant position was calculated. The accuracy evaluated by the 2 methods was also compared. The parameters of the entrance point, apical point, and axis were recorded for each implant. A part of the alignment errors in the digital registration was calculated automatically and recorded. One sample t test and paired t test were conducted by using a statistical software program. RESULTS: The mean deviation between the ideal and postsurgical implant positions evaluated using the digital registration method was 0.84 ±0.57 mm for the entrance point, 1.03 ±0.78 mm for the apical point, and 4.52 ±2.37 degrees for the angulation. No significant difference was found between the accuracy evaluated by the digital registration method and the radiographic method (P>.05). In the digital registration procedure, the alignment error was 0.03 mm for the registration model and 0.29 mm for the dentition. Significant differences were found in the alignment procedure of the impression cylinder (P<.001) and dentition (P<.001). The average positive and negative errors were +0.09 and -0.19 mm for the simulated cylinder of the ideal implant and +0.08 and -0.15 mm for the simulated cylinder of the postsurgical implant. CONCLUSIONS: The precision of the digital registration method could be accepted in clinical applications. No significant difference was found between the digital registration method and the radiographic method in evaluating the clinical accuracy of the implant position. The digital registration method was able to control and minimize the alignment errors produced during data processing.

Evaluation of Mandibular Lingual Foramina With Cone-Beam Computed Tomography.

The aim of this study was to evaluate the characteristics of 3 kinds of mandibular lingual foramina through cone beam computed tomography images to analyze its diameter, frequency, location and its correlation with age in southeast Chinese mainland population. Lingual foramina in 299 patients were grouped into midline lingual foramina (MLF), lateral lingual foramina (LLF), and nutrient foramina (NF) with diameters and frequency measured. Vertical distances from foramina to mandibular inferior border were recorded as Hinf. Data were analyzed using ANOVA, independent sample t tests and Pearson correlation. Results showed that MLF had a frequency of 99.3% at midline symphysis. Average diameter and Hinf of MLF were 0.65 ±â€Š0.19 and 13.79 ±â€Š2.15 mm, respectively. Lateral lingual foramina had a frequency of 63.2% with the majority observed in premolar region. Average diameter and Hinf of LLF were 0.62 ±â€Š0.19 and 6.90 ±â€Š1.88 mm, respectively. Nutrient foramina had a frequency of 91.3% and was most frequently detected between mandibular incisors. Average diameter and Hinf of NF were 0.57 ±â€Š0.15 and 28.39 ±â€Š2.38 mm, respectively. Mean diameter of MLF and NF of each patient correlated with age (r = 0.174 and 0.201, respectively, P < 0.05). No statistical correlation was observed between average diameter of LLF and age (r = 0.114, P > 0.05). Preoperative cone beam computed tomography is a valuable aid in locating lingual foramina, which could be used as an indication to avoid unwanted hemorrhage in implant surgery.

Antibacterial activity, cytotoxicity and mechanical behavior of nano-enhanced denture base resin with different kinds of inorganic antibacterial agents.

Silanized aluminum borate whiskers (ABWs) of 4 wt%, silanized zirconium dioxide nanoparticles (nano-ZrO2) of 2 wt% were mixed with polymethyl methacrylate (PMMA) powder to get ZrO2-ABWs/PMMA composites. Titanium dioxide (TiO2), silver-supported titanium dioxide (Ag/TiO2), silver-supported zirconium phosphate (Novaron) and tetrapod-like zinc oxide whiskers (T-ZnOw) antibacterial agents of 3 wt% were mixed with ZrO2-ABWs/PMMA composites respectively to fabricate standard specimens. Plaque biofilms on the specimens surface were investigated for colony-forming units (CFUs). In addition, cytotoxicity and mechanical behavior were evaluated. Results showed that the CFUs values of S. mutans and C. albican biofilms on the four antibacterial composites surface were all reduced (p<0.05) compared to the blank and control groups. The antibacterial composites did not have an adverse effect on fibroblast growth in this study (p>0.05) except TiO2 and Ag/TiO2 groups of undiluted extracts. The flexural strength and surface hardness of Novaron and T-ZnOw groups were increased (p<0.05) compared to the control group.

In Vitro and in Vivo Activity of Multitarget Inhibitors against Trypanosoma brucei.

We tested a series of amidine and related compounds against Trypanosoma brucei. The most active compound was a biphenyldiamidine that had an EC 50 of 7.7 nM against bloodstream-form parasites. There was little toxicity against two human cell lines with CC 50 > 100 µM. There was also good in vivo activity in a mouse model of infection with 100% survival at 3 mg/kg i.p. The most potent lead blocked replication of kinetoplast DNA (k-DNA), but not nuclear DNA, in the parasite. Some compounds also inhibited the enzyme farnesyl diphosphate synthase (FPPS), and some were uncouplers of oxidative phosphorylation. We developed a computational model for T. brucei cell growth inhibition (R (2) = 0.76) using DNA ΔT m values for inhibitor binding combined with T. brucei FPPS IC 50 values. Overall, the results suggest that it may be possible to develop multitarget drug leads against T. brucei that act by inhibiting both k-DNA replication and isoprenoid biosynthesis.

Clinical marginal and internal fit of metal ceramic crowns fabricated with a selective laser melting technology.

STATEMENT OF PROBLEM: Selective laser melting (SLM) technology has been introduced to fabricate dental restorations. However, the fit of these restorations still needs further study. PURPOSE: The purpose of this in vivo investigation was to compare the marginal and internal fit of SLM metal ceramic crowns with 2 lost-wax cast metal ceramic crowns and to evaluate the influence of tooth type on the marginal and internal fit of these crowns. MATERIAL AND METHODS: A total of 330 metal ceramic crowns were evaluated. The metal copings were fabricated with SLM Co-Cr, cast Au-Pt, and cast Co-Cr alloy (n=110). The marginal and internal gaps of crowns were recorded by using a replica technique. The anterior and premolar replicas were sectioned 2 times, and molar replicas were sectioned 4 times. The marginal and internal gap width of each cross section was examined by stereomicroscope at ×30 magnification. Two-way analysis of variance was performed to identify the statistical difference among the groups. RESULTS: The marginal fit of the SLM Co-Cr group (75.6 ±32.6 µm) was not different from the cast Au-Pt group (76.8 ±32.1 µm) (P>.05) but was better than the cast Co-Cr group (91.0 ±36.3 µm) (P<.01). No significant difference was found among the SLM Co-Cr group (127.3 ±45.8 µm), cast Au-Pt group (129.9 ±61.1 µm). and cast Co-Cr group (142.5 ±63.7 µm) (P>.05). The mean occlusal gap width of the SLM Co-Cr group (309.8 ±106.6 µm) was significantly higher than that of the cast Au-Pt group (254.6 ±109.6 µm) and the cast Co-Cr group (249.6 ±110.4 µm) (P<.005). No significant difference was found in the marginal fit among the anterior group (84.4 ±35.1 µm), the premolar group (80.6 ±26.3 µm), and the molar group (82.7 ±38.0 µm) (P>.05). Also, no significant difference was found in the axial fit among the anterior group (138.3 ±52.5 µm), the premolar group (132.9 ±50.4 µm), and the molar group (134.4 ±52.5 µm) (P>.05). The anterior group (267.6 ±110.2 µm) did not differ from the premolar group (270.2 ±112.8 µm) and the molar group (268.6 ±110.5 µm) in occlusal fit (P>.05). CONCLUSIONS: The marginal fit of SLM Co-Cr metal ceramic crowns was similar to that of the cast Au-Pt metal ceramic crowns and was better than that of the cast Co-Cr metal ceramic crowns. The SLM Co-Cr metal ceramic crowns were not significantly different from the 2 cast metal ceramic crowns in axial fit but were less accurate in occlusal fit. Tooth type did not influence the marginal and internal fit of the metal ceramic crowns.

Clinical Marginal and Internal Fit of Crowns Fabricated Using Different CAD/CAM Technologies.

PURPOSE: The aims of this in vivo investigation were to compare the marginal and internal fit of single-unit crowns fabricated using a selective laser melting (SLM) procedure with two CAD/CAM grinding procedures, and to evaluate the influence of tooth type on the parameters measured. MATERIALS AND METHODS: A total of 270 crowns were evaluated, including 90 SLM metal-ceramic crowns (group B), 90 zirconium-oxide-based ceramic crowns (group L), and 90 lithium disilicate ceramic crowns (group C). The marginal and internal gaps of the crowns were recorded using a replica technique with a silicone indicator paste stabilized with a light-body silicone. The gap replica specimen were sectioned buccolingually and mesiodistally and then examined using a stereomicroscope at 30× magnification. Ten reference points were measured on each anterior and premolar specimen, and 20 reference points were measured on each molar specimen. Two-way ANOVA was performed to identify the significant differences between the groups. RESULTS: The mean marginal fit of group B was significantly better than those of group C and group L (p < 0.005), but a significant difference was not found between group C and group L (p > 0.05). The mean axial gap of group B was significantly smaller than those of group C and group L (p < 0.01), while group C was not different from group L (p > 0.05). The mean occlusal gap of group B was significantly higher than those of group C and group L (p < 0.05), and no difference was found between group C and group L (p > 0.05). The marginal and internal gaps of crowns varying according to tooth type were not significantly different (p > 0.05). CONCLUSION: The SLM system demonstrated better marginal and internal fit compared to the two CAD/CAM grinding systems examined. Tooth type did not significantly influence the marginal or internal fit.

Hybrid effects of zirconia nanoparticles with aluminum borate whiskers on mechanical properties of denture base resin PMMA.

The aim of this study was to investigate the hybrid effects of ZrO2 nanoparticles (nano-ZrO2) and aluminum borate whiskers (ABWs) on flexural strength and surface hardness of denture base resin, polymethyl methacrylate (PMMA). Both nano-ZrO2 and ABWs were modified by silane coupling agent (Z6030) before being mixed with PMMA. Various amounts of silanized nano-ZrO2 and ABWs were mixed with PMMA to prepare ZrO2-ABW/PMMA composites. Flexural strength and surface hardness were evaluated using three- point bending test and Vickers hardness test respectively. Fractured surfaces were also observed by scanning electron microscopy (SEM). The mechanical behaviors of silanized ZrO2-ABW/PMMA composites were significantly improved. Flexural strength reached a maximum value of 108.01 ± 5.54 MPa when 2 wt% of nano-ZrO2 was mixed with ABWs at a ZrO2/ABW ratio of 1:2, amounting to an increase of 52% when compared with pure PMMA. Surface hardness achieved a maximum value of 22.50 ± 0.86 MPa when 3 wt% of nano-ZrO2 was mixed with ABWs at the same ZrO2/ABW ratio, which was an increase of 27% when compared with pure PMMA.