The expanded use of nickel-titanium (NiTi) rotary instruments in root canal procedures has led to the development of a wide variety of shapes, designs and applications. Root canal anatomy has not changed, however, and the same challenges exist in both initial treatment and the revision of unacceptable treatment. These challenges include application with high levels of achievement and low to no levels of adverse effects, such as instrument fracture, root canal wall ledging, dentine wall perforation and so forth. To that end, many manufacturers have been seeking ways to alter the presently available and wide range of root canal instrument designs, with a focus on altering the surface of the alloy or altering the alloy microstructure with post-machining or post-twisting heat treatment. This focused review will address the impact that these modifications have had on instrument flexibility, resistance to cyclic fatigue and cutting efficiency.
Given that only a subset of patients with colorectal cancer (CRC) benefit from immune checkpoint therapy, efforts are ongoing to identify markers that predict immunotherapeutic response. Increasing evidence suggests that microbes influence the efficacy of cancer therapies. Fusobacterium nucleatum induces different immune responses in CRC with different microsatellite-instability (MSI) statuses. Here, we investigated the effect of F. nucleatum on anti-PD-L1 therapy in CRC. We found that high F. nucleatum levels correlate with improved therapeutic responses to PD-1 blockade in patients with CRC. Additionally, F. nucleatum enhanced the antitumor effects of PD-L1 blockade on CRC in mice and prolonged survival. Combining F. nucleatum supplementation with immunotherapy rescued the therapeutic effects of PD-L1 blockade. Furthermore, F. nucleatum induced PD-L1 expression by activating STING signaling and increased the accumulation of interferon-gamma (IFN-γ)+ CD8+ tumor-infiltrating lymphocytes (TILs) during treatment with PD-L1 blockade, thereby augmenting tumor sensitivity to PD-L1 blockade. Finally, patient-derived organoid models demonstrated that increased F. nucleatum levels correlated with an improved therapeutic response to PD-L1 blockade. These findings suggest that F. nucleatum may modulate immune checkpoint therapy for CRC.
SUMMARYMonitoring of complex structures to provide real-time safety and reliability information regarding the structure poses significant technical challenges. To detect damage in large civil infrastructure systems, densely distributed sensors are expected to be required. Use of traditional wired sensors is challenging for such applications because of the cost and difficulty in deploying and maintaining a large wiring plant. Using wireless sensor network is also difficult because large amounts of measured data need to be transferred to a central station. The bandwidth and power requirement to transfer these data may easily exceed the limit of the wireless sensor. Recently rapid advances in smart sensor technologies have made damage detection using a dense array of sensors feasible. The essential feature of a smart sensor is the on-board microprocessor, which allows smart sensors to make decisions, perform computation, save data locally, etc. By conducting a portion of the computation at the sensor level, only limited information needs to be transferred back to a central station. However, damage detection algorithms which can take advantage of the distributed computing environment offered by smart sensors are currently limited.In this paper, a new distributed computing strategy for structural health monitoring is proposed that is suitable for implementation on a network of densely distributed smart sensors. In this approach, a hierarchical strategy is proposed in which adjacent smart sensors are grouped together to form sensor communities. A flexibility-based damage detection method is employed to evaluate the condition of the local elements within these communities by utilizing only locally measured information. The damage detection results in these communities are then communicated with the surrounding communities and sent back to a central station. Numerical simulation demonstrates that the proposed approach works well for both single and multiple damage scenarios.
Emerging research has revealed regulation of colorectal cancer metabolism by bacteria. Fusobacterium nucleatum (Fn) plays a crucial role in the development of colorectal cancer, however, whether Fn infection modifies metabolism in patients with colorectal cancer remains unknown. Here, LC-MS/MS-based lipidomics identified the upregulation of cytochrome P450 monooxygenases, primarily CYP2J2, and their mediated product 12,13-EpOME in patients with colorectal cancer tumors and mouse models, which increased the invasive and migratory ability of colorectal cancer cells in vivo and in vitro by regulating the epithelial–mesenchymal transition (EMT). Metagenomic sequencing indicated a positive correlation between increased levels of fecal Fn and serum 12,13-EpOME in patients with colorectal cancer. High levels of CYP2J2 in tumor tissues also correlated with high Fn levels and worse overall survival in patients with stage III/IV colorectal cancer. Moreover, Fn was found to activate TLR4/AKT signaling, downregulating Keap1 and increasing NRF2 to promote transcription of CYP2J2. Collectively, these data identify that Fn promotes EMT and metastasis in colorectal cancer by activating a TLR4/Keap1/NRF2 axis to increase CYP2J2 and 12,13-EpOME, which could serve as clinical biomarkers and therapeutic targets for Fn-infected patients with colorectal cancer.
Significance:
This study uncovers a mechanism by which Fusobacterium nucleatum regulates colorectal cancer metabolism to drive metastasis, suggesting the potential biomarker and therapeutic utility of the CYP2J2/12,13–EpOME axis in Fn-infected patients.
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