The establishment of protected areas (PAs) is a central strategy for global biodiversity conservation. While the role of PAs in protecting habitat has been highlighted, their effectiveness at protecting mammal communities remains unclear. We analyzed a global dataset from over 8671 camera traps in 23 countries on four continents that detected 321 medium‐ to large‐bodied mammal species. We found a strong positive correlation between mammal taxonomic diversity and the proportion of a surveyed area covered by PAs at a global scale (β = 0.39, 95% confidence interval [CI] = 0.19–0.60) and in Indomalaya (β = 0.69, 95% CI = 0.19–1.2), as well as between functional diversity and PA coverage in the Nearctic (β = 0.47, 95% CI = 0.09–0.85), after controlling for human disturbances and environmental variation. Functional diversity was only weakly (and insignificantly) correlated with PA coverage at the global scale (β = 0.22, 95% CI = −0.02–0.46), pointing to a need to better understand the functional response of mammal communities to protection. Our study provides important evidence of the global effectiveness of PAs in conserving terrestrial mammals and emphasizes the critical role of area‐based conservation in a post‐2020 biodiversity framework.

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Thymoquinone is one of the main components present in Nigella sativa seeds and is known to have various biological functions in inflammation, oxidative stress, tumors, aging, and in lowering blood glucose levels. Few studies have focused on its neuroprotective effects and its regulation of small-molecule metabolites during cerebral ischemia reperfusion injury. In this study, transient middle cerebral occlusion (tMCAO) was used to establish the rat model of cerebral ischemia reperfusion injury. We investigated the effects of thymoquinone using matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) in a model of ischemia reperfusion injury to explore the changes in small-molecule metabolites in the brain. We found that that thymoquinone significantly improved neurobehavioral scores, reduced the cerebral infarct area, alleviated brain edema, and increased the number of normal neurons following injury. MALDI-MSI revealed that thymoquinone reduced abnormal accumulations of glucose, citric acid, succinate and potassium ions. Thymoquinone also increased the amount of energy-related molecules such as ADP, AMP, GMP, and creatine, antioxidants such as glutathione, ascorbic acid, and taurine, and other metabolism-related molecules such as glutamate, glutamine, aspartate, N-acetyl-L-aspartate, and sodium ions in damaged areas of the brain following cerebral ischemia reperfusion injury. In summary, based on the neuroprotective effect of thymoquinone on cerebral ischemia reperfusion injury, this study revealed the regulation of thymoquinone on energy metabolism and small-molecule substance metabolism.

Dl-3-n-butylphthalide (NBP) is a drug that is used in the treatment of ischaemic stroke. However, to the best of our knowledge, there are no systematic studies investigating the effects of dl-3-n-butylphtalide on the brain metabolism of small molecules. In this study, we first investigated the effects of dl-3-n-butylphthalide on the spatial distribution of small molecules in the brains of rats with permanent middle cerebral artery occlusion (pMCAO) using matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI–TOF–MS) imaging. After pMCAO modelling or a sham operation, rats were given four mg/kg of dl-3-n-butylphthalide through the caudal vein or saline once a day for nine days. The degree of neurological deficit in rats was evaluated using the modified neurological severity score (mNSS). MALDI–TOF–MS imaging was used to observe the content and distribution of small molecules related to metabolism during focal cerebral ischaemia. Multiple reaction monitoring (MRM) mode with liquid chromatography tandem mass spectrometry (LC–MS/MS) was used to verify the results obtained from MALDI–TOF–MS imaging. These small molecules were found to be involved in glucose metabolism, ATP metabolism, the glutamate–glutamine cycle, malate aspartate shuttle, oxidative stress, and inorganic ion homeostasis. Of the 13 metabolites identified by MALDI–TOF–MS imaging, seven compounds, ATP, ADP, AMP, GMP, N-acetylaspartic acid, ascorbic acid and glutathione, were further validated by LC–MS/MS. Taken together, these results indicate that dl-3-n-butylphthalide significantly improved ATP metabolism, level of antioxidants, and sodium-potassium ion balance in a rat model of pMCAO.

Dl-3-n-butylphthalide (NBP) has been widely used to treat ischemic stroke in China. To investigate the mechanisms underlying NBP activity, we established a permanent middle cerebral artery occlusion (pMCAO) rat model and injected the rats with 4 mg/kg/d NBP for nine days. We then assessed neuroinflammation, neovascularization and nerve regeneration within the brain. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry imaging (MALDI-TOF MSI) was used to determine the phospholipid distribution, while laser ablation-inductively coupled plasma mass spectrometry imaging (LA-ICP MSI) was used to measure Foxp3, Ki-67 and pCREB levels in the brain. Immunohistochemistry was used to investigate the expression of NLR family pyrin domain containing 3 (NLRP3) and its inflammatory products, caspase-1 and interleukin-1β, in brain tissues. NBP attenuated ischemic damage and ameliorated neurological deficits in rats with pMCAO. In the ischemic brain region, NBP reduced phosphatidylethanolamine (18:0), NLRP3, caspase-1 and interleukin-1β levels, but increased levels of Foxp3, Ki-67, pCREB and several phospholipids. In molecular docking analyses, NBP bound to NLRP3, interleukin-1β, caspase-1, Foxp3, and Ki-67. These results demonstrate that NBP reduces neuroinflammation in brain tissues and promotes nerve and blood vessel regeneration, thus protecting neuromorphology and function.

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