Associations and attributable burdens in late-life exposure to PM2.5 and its major components and depressive symptoms in middle-aged and older adults: A nationwide cohort study.

BACKGROUND: Depression in late life has been associated with reduced quality of life and increased mortality. Whether the chronic fine particular matter (PM2.5) and its components exposure are contributed to the older depression symptoms remains unclear. METHOD: Middle-aged and older adults (>45 years) were selected from the China Health and Retirement Longitudinal Study during the four waves of interviews. The concentrations of PM2.5 and its major constituents were calculated using near real-time data at a spatial resolution of 10 km during the study period. The depressive symptom was evaluated by the Depression Center for Epidemiologic Studies Depression (CES-D)-10 score. The fix-effect model was applied to evaluate the association between PM2.5 and its major constituents with depressive symptoms. Three three-step methods were used to explore the modification role of sleep duration against the depressive symptoms caused by PM2.5 exposure. RESULTS: In our study, a total of 52,683 observations of 16,681 middle-aged and older adults were assessed. Each interquartile range (IQR) level of PM2.5 concentration exposure was longitudinally associated with a 2.6 % (95 % confidence interval [CI]: 1.3 %, 4.0 %) increase in the depression CES-D-10 score. Regarding the major components of PM2.5, OM, NO3-, and NH4+ showed the leading toxicity effects, which could increase the depression CES-D-10 score by 2.2 % (95 %CI: 1.0 %, 3.4 %), 2.2 % (0.6 %, 3.9 %), and 2.0 % (95 %CI: 0.6 %, 3.4 %) correspondingly. Besides, males were more susceptible to the worse depressive symptoms caused by PM2.5 and its major components exposure than female subpopulations. Shortened sleep duration might be the mediator of PM2.5-associated depressive symptoms. CONCLUSION: Our results suggest that long-term exposure to PM2.5 and its major components were associated with an increased risk for depressive symptoms in middle-aged and older adults. Reducing the leading components of PM2.5 may cost-effectively alleviate the disease burden of depression and promote healthy longevity in heavy pollutant countries.

Intranasal Delivery of Curcumin Nanoparticles Improves Neuroinflammation and Neurological Deficits in Mice with Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) represents one of the most severe subtypes of stroke. Due to the complexity of the brain injury mechanisms following ICH, there are currently no effective treatments to significantly improve patient functional outcomes. Curcumin, as a potential therapeutic agent for ICH, is limited by its poor water solubility and oral bioavailability. In this study, mPEG-PCL is used to encapsulate curcumin, forming curcumin nanoparticles, and utilized the intranasal administration route to directly deliver curcumin nanoparticles from the nasal cavity to the brain. By inhibiting pro-inflammatory neuroinflammation of microglia following ICH in mice, reprogramming pro-inflammatory microglia toward an anti-inflammatory function, and consequently reducing neuronal inflammatory death and hematoma volume, this approach improved blood-brain barrier damage in ICH mice and promoted the recovery of neurological function post-stroke. This study offers a promising therapeutic strategy for ICH to mediate neuroinflammatory microenvironments.

Ethnobotanical Knowledge, Nutritional Composition, and Aroma Profile of Vicia kulingiana Bailey: An Underutilized Wild Vegetable Endemic to China.

Vicia kulingiana, an endemic species, serves as a wild and underutilized vegetable traditionally consumed in China. However, ethnobotanical and chemical studies of this species are not available. This study analyzed its associated ethnobotanical knowledge, nutritional composition and aroma profile. Ethnobotanical surveys revealed its diverse traditional uses, especially as a nutritious vegetable. Further analysis showed V. kulingiana leaves to be high in protein, minerals, vitamin E, and dietary fiber. In total, 165 volatile compounds, such as terpenoids, alcohols, and ketones, were identified. Among them, ß-ionone is the most abundant compound with a relative percentage of 8.24%, followed by 2,2,4,6,6-pentamethylheptane (3.2%), 3-(4-methyl-3-pentenyl)furan (2.37%), and linalool (1.68%). Results supported the traditional uses of V. kulingiana's and highlighted its potential as a valuable food source, encouraging further research on its food applications. The documentation of ethnobotanical knowledge contributes to the conservation of this heritage.

A Targeted and Responsive Nanoprodrug Delivery System for Synergistic Glioma Chemotherapy.

Doxorubicin (DOX) is widely used as a chemotherapeutic agent for both hematologic and solid tumors and is a reasonable candidate for glioma treatment. However, its effectiveness is hindered by significant toxicity and drug resistance. Moreover, the presence of the blood-brain barrier (BBB) brings a crucial challenge to glioma therapy. In response, a GSH-responsive and actively targeted nanoprodrug delivery system (cRGD/PSDOX-Cur@NPs) are developed. In this system, a disulfide bond-bridged DOX prodrug (PEG-SS-DOX) is designed to release specifically in the high glutathione (GSH) tumor environment, markedly reducing the cardiotoxicity associated with DOX. To further address DOX resistance, curcumin, serving as a P-glycoprotein (P-gp) inhibitor, effectively increased cellular DOX concentration. Consequently, cRGD/PSDOX-Cur@NPs exhibited synergistic anti-tumor effects in vitro. Furthermore, in vivo experiments validated the superior BBB penetration and brain-targeting abilities of cRGD/PSDOX-Cur@NPs, showcasing the remarkable potential for treating both subcutaneous and orthotopic gliomas. This research underscores that this nanoprodrug delivery system presents a novel approach to inhibiting glioma while addressing resistance and systemic toxicity.

Immunostimulatory gene therapy combined with checkpoint blockade reshapes tumor microenvironment and enhances ovarian cancer immunotherapy.

Immune evasion has made ovarian cancer notorious for its refractory features, making the development of immunotherapy highly appealing to ovarian cancer treatment. The immune-stimulating cytokine IL-12 exhibits excellent antitumor activities. However, IL-12 can induce IFN-γ release and subsequently upregulate PDL-1 expression on tumor cells. Therefore, the tumor-targeting folate-modified delivery system F-DPC is constructed for concurrent delivery of IL-12 encoding gene and small molecular PDL-1 inhibitor (iPDL-1) to reduce immune escape and boost anti-tumor immunity. The physicochemical characteristics, gene transfection efficiency of the F-DPC nanoparticles in ovarian cancer cells are analyzed. The immune-modulation effects of combination therapy on different immune cells are also studied. Results show that compared with non-folate-modified vector, folate-modified F-DPC can improve the targeting of ovarian cancer and enhance the transfection efficiency of pIL-12. The underlying anti-tumor mechanisms include the regulation of T cells proliferation and activation, NK activation, macrophage polarization and DC maturation. The F-DPC/pIL-12/iPDL-1 complexes have shown outstanding antitumor effects and low toxicity in peritoneal model of ovarian cancer in mice. Taken together, our work provides new insights into ovarian cancer immunotherapy. Novel F-DPC/pIL-12/iPDL-1 complexes are revealed to exert prominent anti-tumor effect by modulating tumor immune microenvironment and preventing immune escape and might be a promising treatment option for ovarian cancer treatment.