Human Serum Albumin-Platinum(II) Agent Nanoparticles Inhibit Tumor Growth Through Multimodal Action Against the Tumor Microenvironment.

To overcome the limitations of traditional platinum (Pt)-based drugs and further improve the targeting ability and therapeutic efficacy in vivo, we proposed to design a human serum albumin (HSA)-Pt agent complex nanoparticle (NP) for cancer treatment by multimodal action against the tumor microenvironment. We not only synthesized a series of Pt(II) di-2-pyridone thiosemicarbazone compounds and obtained a Pt(II) agent [Pt(Dp44mT)Cl] with significant anticancer activity but also successfully constructed a novel HSA-Pt(Dp44mT) complex nanoparticle delivery system. The structure of the HSA-Pt(Dp44mT) complex revealed that Pt(Dp44mT)Cl binds to the IIA subdomain of HSA and coordinates with His-242. The HSA-His242-Pt-Dp44mT NPs had an obvious effect on the inhibition of tumor growth, which was superior to that of Dp44mT and Pt(Dp44mT)Cl, and they had almost no toxicity. In addition, the HSA-His242-Pt-Dp44mT NPs were found to kill cancer cells by inducing apoptosis, autophagy, and inhibiting angiogenesis.

Spatiotemporal access to emergency medical services in Wuhan, China: accounting for scene and transport time intervals.

BACKGROUND: Access as a primary indicator of Emergency Medical Service (EMS) efficiency has been widely studied over the last few decades. Most previous studies considered one-way trips, either getting ambulances to patients or transporting patients to hospitals. This research assesses spatiotemporal access to EMS at the shequ (the smallest administrative unit) level in Wuhan, China, attempting to fill a gap in literature by considering and comparing both trips in the evaluation of EMS access. METHODS: Two spatiotemporal access measures are adopted here: the proximity-based travel time obtained from online map services and the enhanced two-step floating catchment area (E-2SFCA) which is a gravity-based model. First, the travel time is calculated for the two trips involved in one EMS journey: one is from the nearest EMS station to the scene (i.e. scene time interval (STI)) and the other is from the scene to the nearest hospital (i.e. transport time interval (TTI)). Then, the predicted travel time is incorporated into the E-2SFCA model to calculate the access measure considering the availability of the service provider as well as the population in need. For both access measures, the calculation is implemented for peak hours and off-peak hours. RESULTS: Both methods showed a marked decrease in EMS access during peak traffic hours, and differences in spatial patterns of ambulance and hospital access. About 73.9% of shequs can receive an ambulance or get to the nearest hospital within 10 min during off-peak periods, and this proportion decreases to about 45.5% for peak periods. Most shequs with good ambulance access but poor hospital access are in the south of the study area. In general, the central areas have better ambulance, hospital and overall access than peripheral areas, particularly during off-peak periods. CONCLUSIONS: In addition to the impact of peak traffic periods on EMS access, we found that good ambulance access does not necessarily guarantee good hospital access nor the overall access, and vice versa.

Developing an Arene Binuclear Ruthenium(II) Complex to Induce Ferroptosis and Activate the cGAS-STING Pathway: Targeted Inhibiting Growth and Metastasis of Triple Negative Breast Cancer.

To effectively inhibit the growth and metastasis of triple-negative breast cancer (TNBC), we developed a high-efficiency and low-toxicity arene ruthenium (Ru) complex based on apoferritin (AFt). To achieve this, we optimized a series of Ru(II) 1,10-phenanthroline-2,9-diformaldehyde thiosemicarbazone complexes by studying their structure-activity relationships to obtain an arene binuclear Ru(II) complex (C5) with significant cytotoxicity and high accumulation in the mitochondria of tumor cells. Subsequently, a C5-AFt nanoparticle (NPs) delivery system was constructed. We found that the C5/C5-AFt NPs effectively inhibited TNBC growth and metastasis with few side effects. The C5-AFt NPs improved the anticancer and targeting abilities of C5 in vivo. Moreover, we confirmed the mechanism by which C5/C5-AFt NPs inhibit tumor growth and metastasis via mitochondrial damage-mediated ferroptosis and activation of the cGAS-STING pathway.

Tunable Electrochemical Activity of P2-Na0.6Mn0.7Ni0.3O2-xFx Microspheres as High-Rate Cathodes for High-Performance Sodium Ion Batteries.

As an important cathode candidate for the high-performance sodium ion batteries (SIBs), P2-type oxides with layered structures are needed to balance the specific capacities and cycling stability. As a result, a cation and anion codoped strategy has been adopted to tune the electrochemical activity of the redox centers and modulate the structure properties. Herein, a series of P2-Na0.6Mn0.7Ni0.3O2-xFx (x = 0, 0.03, 0.05, and 0.07) cathodes with microsphere structures are synthesized, using a solid-state reaction in the presence of MnO2 microsphere self-templates. Compared with the cation-doped Na0.6Mn0.7Ni0.3O2, additional F-doping can affect the lattice parameters and redox centers of Na0.6Mn0.7Ni0.3O2-xFx. Comprehensively considering the specific capacities, cycling stability, and rate capability, the optimized x value in Na0.6Mn0.7Ni0.3O2-xFx is determined to be 0.05. In the half cells, Na0.6Mn0.7Ni0.3O1.95F0.05 (F-0.05) maintains a capacity of 90.5 mA h g-1 in the first cycle at 1.0 A g-1, giving a capacity retention of 78% within 900 cycles. The superior rate capability of F-0.05 is guaranteed by the larger diffusion coefficient of Na+ (DNa) combined with higher charge transfer speed. In addition, when coupled with MoSe2/PC anodes, the full cells also exhibit impressive electrochemical performance.

[Ultrasonic atomization of Shaduolika and dexamethasone for pain relief in patients with foliate papillitis].

PURPOSE: To evaluate the effect of ultrasonic atomization of Shaduolika (a traditional Chinese herb), dexamethasone for pain relief in patients with foliate papillitis. METHODS: 84 patients with foliate papillitis were divided into two groups randomly with the single-blind method. Patients in the experimental group were treated with ultrasonic atomization of Shaduolika and dexamethasone, while patients in the control group were treated by taking Niuhuangjiedu tablets (mixed traditional Chinese medicine). All the patients were observed for five days. Pain relief degree by VAS and the response to the interventions between the experimental and the control group were recorded and compared. The data was analyzed with Ridit test, Chi-square test and Student's t test using SAS6.12 software package, respectively. RESULTS: Pain scores between the experimental and the control group prior to treatment had no significant difference (U=0.1859<1.96, P>0.05), while significant difference existed in pain relief after treatment (U=5.773, P<0.01). The effect of ultrasonic atomization of Shaduolika and dexamethasone for pain relief was significantly better than the control group (U=5.233,P<0.01). CONCLUSIONS: For patients with foliate papillitis, ultrasonic atomization of Shaduolika and dexamethasone is a safe and effective method.