Comparative pharmacokinetics of six components in normal and rheumatoid arthritis rats after intragastrical administration of Qianghuo Shengshi Decoction granules by LC-MS/MS.

Objective: To investigate the plasma pharmacokinetics of six representative components (nodakenin, osthole, 5-O-methylvisammioside, ferulic acid, liquiritigenin, and liquiritin), which were the ingredients of Qianghuo Shengshi Decoction (QSD) granules, in normal and rheumatoid arthritis (RA) rats administrated QSD granules intragastrically. Methods: A rapid and accurate ultra-high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous determination of six components in plasma, and it showed a good specificity, linearity, intra-day and inter-day precision, intra-day and inter-day accuracy, extraction recovery, stability, and the less matrix effect. Results: The validated LC-MS/MS method was successfully used to compare the plasma pharmacokinetics of six ingredients between normal and RA rats after intragastrical administration of QSD granules and differences in the pharmacokinetics were found in two types of rats. The absorption rate in the RA rats was lower for nodakenin, osthole, 5-O-methylvisammioside, liquiritigenin and liquiritin than in the normal group, while the absorption rate of ferulic acid remained constant in two groups. In comparison with the normal rats, the exposure concentration of nodakenin was higher and that of other five components except for nodakenin was lower under pathological conditions. Additionally, the absorptive amount of nodakenin, osthole, 5-O-methylvisammioside and liquiritin was increased and that of ferulic acid and liquiritigenin was reduced in the RA rats than in the normal rats. Compared with the normal rats, the retention time of nodakenin, ferulic acid and liquiritin was reduced in vivo, whereas the retention time of osthole, 5-O-methylvisammioside and liquiritigenin was raised in the body for the RA rats. In contrast to the normal rats, the data demonstrated an increase in the elimination velocity of nodakenin and a decrease in the elimination velocity of the other five components except for nodakenin in the pathological state. Conclusion: This study showed that the pharmacokinetic behavior of the six components, nodakenin, osthole, 5-O-methylvisammioside, ferulic acid, liquiritigenin, and liquiritin, is different in vivo between normal and pathological states of rats, and this research provided the necessary experimental data to explain the pharmacokinetics of QSD granules in both normal and pathological states and provide some references for its clinical application at some level.

Influence of Laser Process Parameters on the Forming Quality and Discharge Performance of 3D-Printed Porous Anodes for Al-Air Batteries.

Aluminum-air (Al-air) batteries are considered one of the most promising next-generation energy storage devices. In this paper, we carry out an orthogonal experimental study on the SLM printing process parameters in 3D-printed Al-air battery anodes. The surface roughness, densification, and discharge performance of the electrodes under different process parameters are observed to reveal the effects of different process parameters on the forming quality and discharge performance of aluminum-air battery anodes. The results show that the laser power is the most important factor affecting the surface roughness of the porous aluminum anode, and the scanning spacing is the most important factor affecting the densification. The best printing parameters for the porous aluminum anode can be obtained when the laser power is 325 W, the scanning speed is 1000 mm/s, the scanning spacing is 0.12 mm, and the thickness of the powder spread is 0.03 mm. At this time, the surface roughness of the porous aluminum anode obtained by this process parameter is 15.01 µm, the densification is 94.97%, and the discharge is stable with a high value. In addition, we also carry out data validation to ensure that the data we obtain are optimal and valid.

Application of hyaluronic acid-based nanoparticles for cancer combination therapy.

Cancer is a significant public health problem in the world. The treatment methods include surgery, chemotherapy, phototherapy, and immunotherapy. Due to their respective limitations, the treatment effect is often unsatisfactory, laying hidden dangers for metastasis and recurrence. Since their exceptional biocompatibility and excellent targeting capabilities, hyaluronic acid-based biomaterials have generated great interest as drug delivery methods for tumor therapy. Moreover, modified HA can self-assemble into hydrogels or nanoparticles (NPs) for precise drug administration. This article summarizes the application of HA-based NPs in combination therapy. Ultimately, it is anticipated that this research will offer guidance for creating various HA-based NPs utilized in numerous cancer therapies.

Smart Responsive and Controlled-Release Hydrogels for Chronic Wound Treatment.

Chronic wounds are a major health challenge that require new treatment strategies. Hydrogels are promising drug delivery systems for chronic wound healing because of their biocompatibility, hydration, and flexibility. However, conventional hydrogels cannot adapt to the dynamic and complex wound environment, which involves low pH, high levels of reactive oxygen species, and specific enzyme expression. Therefore, smart responsive hydrogels that can sense and respond to these stimuli are needed. Crucially, smart responsive hydrogels can modulate drug release and eliminate pathological factors by changing their properties or structures in response to internal or external stimuli, such as pH, enzymes, light, and electricity. These stimuli can also be used to trigger antibacterial responses, angiogenesis, and cell proliferation to enhance wound healing. In this review, we introduce the synthesis and principles of smart responsive hydrogels, describe their design and applications for chronic wound healing, and discuss their future development directions. We hope that this review will inspire the development of smart responsive hydrogels for chronic wound healing.

Phytoestrogen-derived multifunctional ligands for targeted therapy of breast cancer.

Nano-targeted delivery systems have been widely used for breast tumor drug delivery. Estrogen receptors are considered to be significant drug delivery target receptors due to their overexpression in a variety of tumor cells. However, targeted ligands have a significant impact on the safety and effectiveness of active delivery systems, limiting the clinical transformation of nanoparticles. Phytoestrogens have shown good biosafety characteristics and some affinity with the estrogen receptor. In the present study, molecular docking was used to select tanshinone IIA (Tan IIA) among phytoestrogens as a target ligand to be used in nanodelivery systems with some modifications. Modified Tan IIA (Tan-NH2) showed a good biosafety profile and demonstrated tumor-targeting, anti-tumor and anti-tumor metastasis effects. Moreover, the ligand was utilized with the anti-tumor drug Dox-loaded mesoporous silica nanoparticles via chemical modification to generate a nanocomposite Tan-Dox-MSN. Tan-Dox-MSN had a uniform particle size, good dispersibility and high drug loading capacity. Validation experiments in vivo and in vitro showed that it also had a better targeting ability, anti-tumor effect and lower toxicity in normal organs. These results supported the idea that phytoestrogens with high affinity for the estrogen receptor could improve the therapeutic efficacy of nano-targeted delivery systems in breast tumors.

Photoacoustic imaging-guided triple-responsive nanoparticles with tumor hypoxia relief for improving chemotherapy/ photothermal/photodynamic synergistic therapy against breast cancer.

Chemo-photothermal/photodynamic synergistic therapy is a new effective cancer treatment method to overcome the limitations of single chemotherapy. However, the limited low photothermal conversion efficiency, the hypoxic tumor microenvironment, and premature leakage of the drug constrain their clinical applications. To address these challenges, an all-in-one biodegradable polydopamine-coated UiO-66 framework nanomedicine (DUPM) was developed to co-deliver the drug doxorubicin hydrochloride (DOX) and the excellent photothermal material MoOx nanoparticles (NPs). The results showed that DUPM exhibited good physicochemical stability and efficiently accumulated tumor tissues under pH-, glutathione-, and NIR-triggered drug release behaviour. Of note, the synthesized MoOx NPs endowed DUPM with self-supporting oxygen production and generated more reactive oxygen species (1O2 and·OH), besides, it induces Mo-mediated redox reaction to deplete excessive glutathione thus relieving tumor hypoxia to enhance PDT, further improving synergistic therapy. Meanwhile, DUPM showed strong absorption in the near-infrared range and high photothermal conversion efficiency at 808 nm (51.50%) to realize photoacoustic imaging-guided diagnosis and treatment of cancer. Compared with monotherapy, the in vivo anti-tumor efficacy results showed that DUMP exerted satisfactory tumor growth inhibition effects (94.43%) with good biocompatibility. This study provides a facile strategy to develop intelligent multifunctional nanoparticles with tumor hypoxia relief for improving synergistic therapy and diagnosis against breast cancer.

Changes in Physical Activity and Health Indicators among Koreans during the COVID-19 Pandemic: Comparison between 2019 and 2020.

This study aimed to compare the changes in physical activity (PA), chronic disease, and mental health indicators of Koreans before and after the COVID-19 outbreak, using raw data from more than 400,000 representative samples from the 2019-2020 Community Health Survey by the Korea Centers for Disease Control and Prevention, and to explore the correlations among them. We used two-way ANOVA to analyze changes and differences in PA and obesity levels. We assessed the influence of gender and recurrent PA using chi-square tests for mental health status and chronic disease. Finally, we performed a correlation analysis to determine the relationships among PA days, mental health, and chronic disease. The results showed that, compared to the levels before the COVID-19 period, moderate-intensity (Days: 1.415~1.217; Time: 114.688~107.321) and high-intensity (Days: 0.798~0.671; Time: 112.866~106.110) PA significantly decreased in Koreans during the COVID-19 period, while low-intensity (Time: 60.305~61.735) PA increased. Before and during the COVID-19 period, men (18,436 (8.1%)~16,124 (7.0%)) performed PA more regularly than women (13,207 (5.8%)~9382 (4.1%)). Compared to the number of regular PA participants before the COVID-19 period, regular PA participants (male, female) decreased from 31,643 (13.8%) to 25,506 (11.1%) during the COVID-19 period. Compared with the levels before the COVID-19 period, the experience rates of stress (3.1%~2.6%), depression (0.8%~0.6%), HBP (3.0%~2.2%), and diabetes (1.2%~0.9%) significantly changed under different levels of conventional PA intervention. In addition, the obesity rate during the COVID-19 period (23.957) was higher than it was before COVID-19 (23.477). During the COVID-19 period, the PA of Koreans was greatly restricted, but low-intensity PA was maintained and increased. PA is an effective activity for maintaining mental health and for preventing and reducing chronic diseases. Recommendations for appropriate intensity or a combination of high-, moderate-, and low-intensity PA should be based on the health status of Koreans to help them maintain mental health and to reduce the risk of chronic diseases during COVID-19 social distancing.