An Exosome-Based Therapeutic Strategy Targeting Neuroinflammation in Alzheimer's Disease with Berberine and Palmatine.

Introduction: Neuroinflammation is one of the major pathogeneses in Alzheimer's disease (AD) and mainly involves abnormal inflammatory activation of microglia by multiple pathological stimuli. The treatment of AD remains a major challenge due to the multifactorial characterization of AD and the inefficient ability of therapeutic drugs to permeate through the blood‒brain barrier (BBB). Accordingly, drug combination treatment and drug carrier delivery have become important therapeutic tools for the treatment of multifactorial diseases, especially AD. Methods: Inflammatory cytokine levels in microglia, including NO, TNF-α, IL-1ß, IL-4, and IL-10, were detected. The Morris water maze and object location task were used to investigate the learning and memory functions of APP/PS1 mice in different treatment groups. The number of neurons and plasticity of synapses were evaluated by immunofluorescence double labelling. Additionally, the ratio of ß-amyloid plaques and the number of activated microglia were evaluated by immunofluorescence staining. The concentrations of ß-amyloid plaques and inflammatory factors in the hippocampus were determined by ELISA. Microglia-derived exosomes (Exos) were extracted and purified by size exclusion chromatography. The distribution of exosomes and drugs was investigated in vitro and in vivo. Results: Compared to single drug interventions, the combination of Ber and Pal (Ber/Pal) modulated microglial inflammatory cytokine levels. Ber/Pal promoted the recovery of learning and memory impairment in APP/PS1 mice. Immunofluorescence staining indicated that Ber/Pal restored neurons, inhibited Aß plaque formation and microglial activation, and regulated the secretion of inflammatory factors. Exos promoted the accumulation of drugs in cells and tissues and improved the targeting of drugs across the BBB. Conclusion: Ber/Pal could offer a synergistic and more comprehensive therapeutic effect in AD. Additionally, the microglia-derived Exos-Ber/Pal delivery system promoted the targeting and permeation of drugs into the brain, suggesting a creative strategy for targeting AD therapy by regulating neuroinflammation in microglial cells.

Can financial development improve environmental quality? New findings from spatial measures of Chinese urban panel data.

China's economy has achieved remarkable success, while it has also paid a high environmental cost. Environmental pollution not only causes great economic losses, but also severely restricts the development of society. Both theory and practice demonstrate that financial development plays a significant role in environmental governance, but the internal mechanism of its impacts has remained to be explored. It is vital to investigate the influence mechanism of financial development on the environmental quality in order to accomplish sustainable economic development through finance and enhance environmental quality concurrently. This paper, using mediating model, spatial Durbin and spatial error model, constructs a theoretical framework financial development on environmental quality from two dimensions, i.e., Financial Interrelations Ratio (FIR) and Financial Efficiency (FE), based on panel data of 234 cities in China from 2010 to 2019. And the results are as follows: (1) the improvement of Financial Interrelations Ratio (FIR) and Financial Efficiency (FE) had not yet reached the level of environmental pollution improvement; (2) in terms of mechanism, the rise of the level of financial development promoted economic growth, but inhibited the optimization of industrial structure, which increased industrial pollution emissions and deteriorates environmental quality; (3) urban environment had significant spatial dependence; (4) the impact of financial development on environmental quality in eastern region has been transformed into an improvement effect, while it still shows a deteriorating effect in central and western regions. Some policy recommendations related to the use of financial development to improve environmental quality are proposed at last, which will help to promote ecological protection and high quality synergistic economic development in China.

Improving Water Quality in the Short Beach Neighborhood of Branford, Connecticut, 2019-A Citizen Science Project.

We initiated a collaboration between local government, academia, and citizen scientists to investigate high frequencies of elevated Escherichia coli bacteria levels in the coastal Short Beach neighborhood of Branford, Connecticut. Citizen scientist involvement enabled collection of short-duration postprecipitation outfall flow water samples (mean E. coli level = 4930 most probable number per 100 mL) and yielded insights into scientific collaboration with local residents. A records review and sanitary questionnaire identified aging properties with septic systems (3.3%) and holding tanks (0.6%) as potential sources of the E. coli contamination. (Am J Public Health. 2022;112(9):1261-1264. https://doi.org/10.2105/AJPH.2022.306943).

AdoR-1 (Adenosine Receptor) Contributes to Protection against Paraquat-Induced Oxidative Stress in Caenorhabditis elegans.

AdoR-1, the single adenosine receptor homolog in Caenorhabditis elegans, which belongs to the superfamily of G-protein coupled receptors (GPCRs), mediates most of the physiological effects of extracellular adenosine. Adenosine has been proved to improve the survival rate of C. elegans in oxidative stress conditions. However, the potential mechanism of adenosine's protective effect against oxidative stress via AdoR-1 has not been studied. In this study, C. elegans were divided into three groups: two groups with paraquat treatment, one in the presence and one in the absence of adenosine, and an untreated control group. Results indicate that many differentially expressed genes were found to be enriched significantly in neural-related signaling pathways among transcriptome data of three groups. Further gene network analysis showed that some important genes well known to be involved in promoting the acetylcholine release pathway, such as dop-1, egl-30, and unc-13, and those involved in promoting the neuropeptide release pathway, such as kin-1, were upregulated by paraquat induction but downregulated after adenosine treatment. Meanwhile, a completely opposite trend was observed for the goa-1 gene that inhibits the acetylcholine-release and neuropeptide-release pathway. Additionally, some biochemical assays including SOD, GSSG, GSH, and AChE were measured to identify the potential protection of adenosine against oxidative stress between wild-type strain N2 and ador-1 gene knockout strain EG6890. Conclusively, our study revealed series of adenosine receptor-mediated genes in C. elegans that might act as regulators of paraquat-induced oxidative stress and may indicate adenosine's promising protective effects.

Palladium-Catalyzed Controllable Reductive/Oxidative Heck Coupling between Cyclic Enones and Thiophenes via C-H Activation.

Herein, we report a straightforward, environmentally friendly, and controllable palladium/ligand catalytic system to enable reductive/oxidative Heck reactions of cyclic enones with thiophene or furan derivatives via C-H activation. The key to this tunable reaction is the appropriate intercepting thienyl-Pd(II)-enolate during the enolization process. Such a controllable and economic protocol would not only provide efficient methods to construct various value-added ß-heteroarylated cyclic ketones/enones but also shed light on developing other conjugate addition reactions via C-H activation.

The maintenance of stable yield and high genetic diversity in the agricultural heritage torreya tree system.

BACKGROUND: Understanding how traditional agriculture systems have been maintained would help design sustainable agriculture. In this study, we examined how farmers have used two types of local trees (Torreya grandis) for stable yield and maintaining genetic diversity in the "globally important agricultural heritage torreya tree system". The two type of torreya trees are grafted torreya (GT) tree and non-grafted-torreya (NGT) tree. The GT tree has only female and was used to produced seed yields. The NGT tree has both male and female and was used to support GT tree by providing pollens and rootstocks. We first tested the ratio of GT tree to NGT tree, their age groups, ratio of female trees (including GT and NGT trees) to male, and the flowering period of GT and NGT trees. We then tested seed yields and genetic diversity of GT and NGT trees. We further tested gene flow among NGT trees, and the relationship of gene flow with exchange rates of pollens and seeds. RESULTS: GT and NGT trees (male and female) were planted in a mosaic pattern with a ratio of 4:1 (GT:NGT). In this planting pattern, one NGT male trees provided pollen for 20 female trees of GT and NGT. The trees were classified into four age groups (I = 100-400 years old; II = 400-700 years old; III = 700-1000 years old; and IV = 1000-1300 years old) based on basal diameter. The entire flowering period was longer for NGT trees than for GT trees that ensured GT trees (which lack of males) being exposed to pollens. GT tree had high and stable seed yield that increased with age groups. High genetic diversity has been maintained in both rootstocks of the GT trees and NGT trees. There was a strong gene flow among NGT trees, which positive correlated with the exchange rates of pollens and seeds. CONCLUSIONS: Our results suggest that farmers obtain stable seed yields, and maintain high genetic diversity by ingeniously using the local GT tree as yield producer and NGT tree as supporter. These GT and NGT trees together ensure sustainable torreya production.

3D Arrays of Super-Hydrophobic Microtubes from Polypore Mushrooms as Naturally-Derived Systems for Oil Absorption.

Porous materials derived from natural resources, such as Luffa sponges, pomelo peel and jute fibres, have recently emerged as oil adsorbents for water purification, due to their suitability, low environmental impact, biodegradability and low cost. Here we show, for the first time, that the porosity of the fruiting body of polypore mushrooms can be used to absorb oils and organic solvents while repelling water. We engineered the surface properties of Ganoderma applanatum fungi, of which the fruiting body consists of a regular array of long capillaries embedded in a fibrous matrix, with paraffin wax, octadecyltrichlorosilane (OTS) and trichloro(1H,1H,2H,2H-perfluorooctyl)silane. Morphological and wettability analyses of the modified fungus revealed that the OTS treatment was effective in preserving the 3D porosity of the natural material, inducing super-hydrophobicity (water contact angle higher than 150°) and improving oil sorption capacity (1.8⁻3.1 g/g). The treated fungus was also inserted into fluidic networks as a filtration element, and its ability to separate water from chloroform was demonstrated.