No abstract

clinical cancer treatments. [1] Though some conventional methods, such as surgery, radiotherapy, and chemotherapy, have been used to treat malignant melanoma in clinics, these methods have exhibited limited treatment efficiencies in inhibiting tumor growth, leading to low patient survival rates. Therefore, more creative and efficient ways are urgently needed to overcome these clinical bottlenecks; for instance, gene therapy, photodynamic therapy (PDT), photothermal therapy, sonodynamic therapy (SDT), and immunotherapy. [2][3][4][5][6] However, due to the diversity, complexity, and heterogeneity of the MM tumor, [7] mono-modal therapy has been found to show limited treatment efficiency for MM tumors. Consequently, searching for integrated therapeutic strategies with multi-modal therapeutics is highly necessary to achieve remarkable antitumor effects. [8][9][10][11][12] The SDT and PDT have been selected as potential clinical methods for treating a wide range of superficial and localized tumors. They utilize the sono-irradiation or photoexcitation to generate highly reactive oxygen species (ROS), such as singlet oxygen ( 1 O 2 ) and hydroxyl radicals (•OH). [13][14][15][16][17] Owing to the temporal and spatial management over the localization of the sound or light, the ROS can be generated precisely in the tumor tissues instead of normal tissue, thus minimizing the side effects. [18][19][20] The unique quantity of deep tissue penetration and little side The diversity, complexity, and heterogeneity of malignant tumor seriously undermine the efficiency of mono-modal treatment. Recently, multi-modal therapeutics with enhanced antitumor efficiencies have attracted increasing attention. However, designing a nanotherapeutic platform with uniform morphology in nanoscale that integrates with efficient chem-/sono-/phototrimodal tumor therapies is still a great challenge. Here, new and facile Pd-single-atom coordinated porphyrin-based polymeric networks as biocatalysts, namely, Pd-Pta/Por, for chem-/sono-/photo-trimodal tumor therapies are designed. The atomic morphology and chemical structure analysis prove that the biocatalyst consists of atomic Pd-N coordination networks with a Pd-N 2 -Cl 2 catalytic center. The characterization of peroxidase-like catalytic activities displays that the Pd-Pta/Por can generate abundant •OH radicals for chemodynamic therapies. The ultrasound irradiation or laser excitation can significantly boost the catalytic production of 1 O 2 by the porphyrin-based sono-/photosensitizers to achieve combined sono-/photodynamic therapies. The superior catalytic production of •OH is further verified by density functional theory calculation. Finally, the corresponding in vitro and in vivo experiments have demonstrated their synergistic chem-/sono-/photo-trimodal antitumor efficacies. It is believed that this study provides new promising single-atom-coordinated polymeric networks with highly efficient biocatalytic sites and synergistic trimodal therapeutic effects, which may inspire many new findings in rea...

The extensive research into developing new nanomedicines during the past few years has witnessed significant progress in diverse biomedical fields, especially for combating drug resistance in antitumor and antibacterial therapies. Recently, transition-metal-based enzymatic nanoagents (TM-EnzNAs) with catalytic production of reactive oxygen species (ROS) have been designed and intensively explored, which have become powerful nanoplatforms and exciting research frontiers in constructing next-generation nanotherapeutics to combat drug-resistant tumors and bacteria. Here, the focus is on the recent design, fundamental principles, and material chemistries in developing and applications of TM-EnzNAs. At first, the different ROS-producing mechanisms and the key factors to enhance ROS level are carefully concluded, and the analytic methods are systematically summarized. Then, the rationally engineered TM-EnzNAs via different synthetic approaches with high ROS producing efficiencies are comprehensively discussed, especially the catalytic activities, mechanisms, and structure-function relationships. After that, the representative applications of these ROS-catalytic TM-EnzNAs for antitumor and bacterial eradication are summarized in detail. Finally, the primary challenges and future perspectives have also been outlined. It is anticipated new therapeutic insights into combating drug-resistant tumors and bacteria will be provided, and significant new inspiration for designing future enzymatic nanoagents is offered.

This study revealed that the site, sex, and age should be taken into account when determining the reference ranges of normal skin elasticity by skin elasticity measurements.

Background: To evaluate the value of shear wave elastography (SWE) in the detection of diabetic peripheral neuropathy (DPN) of the median and tibial nerves. Methods:The study included 40 DPN patients, 40 diabetic mellitus (DM) patients without DPN, and 40 healthy subjects. High-resolution ultrasonography (US) and SWE were performed on the median nerve (MN) and tibial nerve (TN), and cross-sectional area (CSA) and nerve stiffness were measured. ROC analysis was also performed. Results:The patients with DPN demonstrated higher stiffness of the median and tibial nerve compared with that of healthy volunteers and DM patients (P<0.001). Bilateral analysis showed that there was no significant difference in nerve stiffness between the left and right median nerves and tibial nerves in DPN patients (P>0.05). The stiffness of median nerve and tibial nerve in each one side also had no significant difference in patients with DPN (P>0.05). The CSA of the tibial nerve in the DPN group was significantly larger than that in the other groups (P<0.001), while there was no significant difference of median nerve CSA among the three groups (P>0.05). The area under curve (AUC) of SWE (MN: 0.899, TN: 0.927) to diagnose DPN was significantly greater than that of CSA (TN: 0.798). The optimal cut-off value in SWE of the tibial nerve and median nerve for diagnosis of DPN was 4.11 and 4.06 m/s, respectively, with a good sensitivity and specificity.Conclusions: Median and tibial nerve stiffness was significantly higher in patients with DPN. These findings suggest that SWE-based stiffness measurement of the nerve was a better method than CSA, and it can be used as another effective assistant method in the diagnosis of DPN.