The aim of this retrospective cross-sectional study was to comprehensively assess masticatory function in maxillectomy patients with functioning removable prostheses. Their general and oral profiles, the measurement values of their oral functions, including masticatory function, and the history of tumor therapy were extracted from medical charts. The correlations of masticatory function with numerical data and the effects of tumor therapy-related factors on masticatory function were evaluated. In addition, a stepwise conditional logistic regression analysis was performed to identify the potential predictive factors comprehensively. The data from 55 maxillectomy patients revealed that the median value of masticatory function (138.0 mg/dL) was higher than the threshold (100.0 mg/dL) based on the concept of oral hypofunction. Moderate correlations of masticatory function with the number of remaining teeth, the number of functioning occlusal supports, and maximum occlusal force were found, as well as a weak correlation with maximum tongue pressure. These variables also showed statistically significant coefficients (p < 0.01). No significant effect of each tumor therapy-related factor on masticatory function was detected. A logistic regression analysis identified the number of functioning occlusal supports as a significant predictive factor. These results implied the crucial interactions of masticatory function with various factors and the specificities of maxillectomy patients.

Ultrasound-responsive nanodroplets (NDs) targeting tumors have shown great potential in ultrasound imaging and tumor therapy, but most of these studies are based NDs with lipid shells that cannot overcome the uptake by cells of the reticulo-endothelial system (RES). NDs with shells comprised of polyethylene glycol (PEG)-based polymers could effectively suppressed the uptake of RES, but the phase transition, contrast-enhanced imaging and drug release about these NDs have not been well illuminated.
Folate receptor targeted NDs with shells of polymers and loaded with DOX (FA-NDs/DOX) were prepared. The particle size distribution and morphology of NDs was characterized with dynamic light scattering (DLS) and microscope. Phase transition and contrast-enhanced ultrasound imaging under different mechanical indices (MIs) was studied, and the intensity of contrast enhancement were quantitatively analyzed. The targeting property of FA-NDs/DOX to MDA-MB-231 cells and cellular uptake were observed using a fluorescence microscope. The anti-tumor effects of FA-NDs/DOX combined with low-intensity focused ultrasound (LIFU) was studied through cytotoxicity tests. Flow cytometry assays were used to detect cell apoptosis.
The average particle size of the FA-NDs/DOX was 448.0 ± 8.9 nm, and the zeta potential was 30.4 ± 0.3 mV. When exposed to ultrasound at 37 °C, ultrasound contrast enhancement of FA-NDs/DOX was observed when MI ≥0.19. A stronger acoustic signal was observed under higher MIs and concentrations. The results of quantitative analysis showed that the contrast enhancement intensity of FA-NDs/DOX (1.5 mg/mL) at MI of 0.19, 0.29 and 0.48 was 26.6 ± 0.9 dB, 97.0 ± 3.8 dB and 153.1 ± 5.7 dB, respectively. The contrast enhancement of the FA-NDs/DOX lasted for more than 30 minutes at an MI of 0.48. In targeting experiments, FA-NDs could be recognized by MDA-MB-231 cells, and significant cellular uptake was observed. The blank FA-NDs showed good biocompatibility, while the FA-NDs/DOX induced apoptosis of MDA-MB-231 and MCF-7 cells. By combining LIFU irradiation and FA-NDs/DOX treatment, the best cell-killing effect was achieved.
The FA-NDs/DOX prepared in this study has excellent performance in contrast-enhanced ultrasound imaging, tumor targeting and enhanced chemotherapy. This FA-NDs/DOX with polymer shells provides a novel platform for ultrasound molecular imaging and tumor therapy.

Pyroptosis, also known as cellular inflammatory necrosis, is a programmed cell death mediated by the Gasdermin family of proteins. The mechanisms by which pyroptosis occurs are divided into the GSDMD-mediated Caspase-1 and Caspase-4/-5/-11-dependent classical inflammatory vesicle pathway and the GSDME-mediated Caspase-3 and granzyme-dependent non-classical inflammatory vesicle pathways, among others. Recent studies have shown that pyroptosis has both inhibitory and promotive effects on tumor development. Pyroptosis induction also plays a dual role in antitumor immunotherapy: on the one hand, it suppresses antitumor immunity by promoting the release of inflammatory factors, and on the other hand, it inhibits tumor cell proliferation by triggering antitumor inflammatory responses. In addition, cell scorching plays an essential role in chemotherapy. It has been found that natural drugs modulating the induction of cell scorch are necessary to treat tumors. Therefore, studying the specific mechanisms of cell pyroptosis in different tumors can provide more ideas for developing oncology drugs. In this paper, we review the molecular mechanisms of pyroptosis and the role of pyroptosis in tumor development and treatment to provide new targets for clinical tumor treatment, prognosis, and antitumor drug development.

As a regulatory cell death mode defined in recent years, Ferroptosis is mainly characterized by increased intracellular free iron and the accumulation of lipid peroxides. Ferroptosis is closely related to iron ion metabolism, lipid metabolism, and amino acid metabolism. Cancer is the second leading cause of death worldwide, and effective removal of tumour cells while protecting normal cells is the key to tumour treatment. The continuous development and refinement of molecular mechanisms related to ferroptosis have shown promising applications in tumour therapy. There is increasing evidence that triggering ferroptosis in tumour cells is expected to be a new therapeutic strategy for tumour treatment.

The cytolethal distending toxin (CDT), Haemophilus ducreyi, is one of the bacterial toxins that have recently been considered for targeted therapies, especially in cancer therapies. CDT is an A-B2 exotoxin. Its catalytic subunit (CdtB) is capable of inducing DNA double strand breaks, cell cycle arrest and apoptosis in host eukaryotic cells. The sequence alignment indicates that the CdtB is structurally homologyr to phosphatases and deoxyribonucleases I (DNase I). Recently, it has been found that CdtB toxicity is mainly related to its nuclease activity. The immunogenicity of CDT can reduce its effectiveness in targeted therapies. However, the toxin can be very useful if its immunogenicity is significantly reduced. Detecting hotspot ectopic residues by computational servers and then mutating them to eliminate B-cell epitopes is a promising approach to reduce the immunogenicity of foreign protein-based therapeutics. By the mentioned method, in this study, we try to reduce the immunogenicity of the CdtB- protein sequence. This study initially screened residue of the CdtB is B-cell epitopes both linearly and conformationally. By overlapping the B-cell epitopes with the excluded conserve residues, and active and enzymatic sites, four residues were allowed to be mutated. There were two mutein options that show reduced antigenicity probability. Option one was N19F, G74I, and S161F with a VaxiJen score of 0.45 and the immune epitope database (IEDB) score of 1.80, and option two was N19F, G74I, and S161W with a VaxiJen score of 0.45 and IEDB score of 1.88. The 3D structure of the proposed sequences was evaluated and refined. The structural stability of native and mutant proteins was accessed through molecular dynamic simulation. The results showed that the mutations in the mutants caused no considerable changes in their structural stability. However, mutant 1 reveals more thermodynamic stability during the simulation. The applied approaches in this study can be used as rough guidelines for finding hot spot immunogen regions in the therapeutic proteins. Our results provide a new version of CdtB that, due to reduced immunogenicity and increased stability, can be used in toxin-based drugs such as immunotoxins.

We previously proved the superiority of the ligand reversible shielding strategy based on the pH-responsive self-assembly/disassembly of gold nanoparticles through computed tomography imaging in vivo. Herein, the practicality of this strategy in tumor therapy was investigated by a ligand reversible shielding system based on a temperature-responsive polymer. The ligand biotin, cisplatin-loaded chain poly(acrylic acid)-Pt, and the shielding segment thermo-sensitive poly(N-isopropylacrylamide-co-acrylamide) (P(NIPAAm-co-AAm)) were co-modified onto the surface of gold nanostars. In the blood circulation (37 °C), the ligand was shielded by the extension of P(NIPAAm-co-AAm), whose lower critical solution temperature (LCST) is approximately 39 °C. After the nanoparticles accumulate at the tumor site by the enhanced permeability and retention (EPR) effect, the heat generated from gold nanostars upon near-infrared light irradiation would trigger the contraction of P(NIPAAm-co-AAm), thus deshielding the ligand for enhanced tumor cellular uptake. Owing to the reversible extension-contraction transformation change of P(NIPAAm-co-AAm), the reversible shielding effect on the ligand could be accomplished even if the nanoparticles return to the blood circulation. The results indicated that the system could extend blood circulation (1.6-fold at 24 h), reduce immune system clearance (28% lower), and enhance tumor accumulation (37% higher) effectively compared with the irreversible ligand shielding system by analysis of platinum. This strategy showed significantly superior tumor inhibition (11% higher) than the irreversible system. All these results make clear that the ligand reversible shielding strategy is effective and offers important references for the design of nanomaterials for improving tumor accumulation. STATEMENT OF SIGNIFICANCE: Herein, the practicality of the ligand reversible shielding strategy in tumor therapy was investigated. The ligand biotin, cisplatin loaded chain poly(acrylic acid)-Pt and the shielding segment thermo-sensitive poly(N-isopropylacrylamide-co-acrylamide) (P(NIPAAm-co-AAm) which LCST is about 39 °C) were co-modified onto the surface of gold nanostars. This well-designed NPs could shield target ligand in blood circulation (37 °C) and deshield it at tumor site (40-41 °C) reversibly. The results indicated that the system could extend blood circulation (1.6-fold at 24 h), reduce immune system clearance (28% lower) and enhance tumor accumulation (37% higher) effectively compared with the irreversible ligand shielding system by analysis of platinum. Significantly, the strategy showed superior tumor inhibition than the irreversible system (11% higher).