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Objective: Methamphetamine (METH) exposure is commonly believed to result in cognitive impairment. Histamine H3 receptor (H3R) antagonists reportedly have potential applications for treating cognitive impairment accompanied by various neuropsychiatric disorders. The present study aimed to investigate the effect of H3R blockade by Thioperamide (THIO) on METH-induced cognitive impairment and the underlying mechanism., Methods: In Experiment 1, C57BL/6 mice received daily injections of saline or 5 mg/kg METH for 5 consecutive days. The Novel Object Recognition (NOR) and Morris water maze (MWM) tasks were used to assess cognitive functions of mice. H3R protein expression and apoptosis were subsequently measured in the hippocampus. In Experiment 2, HT22 cells were first treated with ddH 2 O or 3 mM METH. The cell survival rate and H3R protein level were subsequently assessed. In Experiment 3, the animals were first treated with saline or 20 mg/kg THIO for 7 days, followed by co-administration of either saline or 5 mg/kg METH for an additional 5 days. The remaining experiments were carried out in the same manner as Experiment 1. In Experiment 4, HT22 cells were pretreated with either ddH 2 O or 5 mM THIO for 2 h, followed by ddH 2 O or 3 mM METH treatment for an additional 12 h. The remaining experiments were carried out in the same manner as Experiment 2. In Experiment 5, the changes in MEK1/2, p-MEK1/2, ERK1/2 and p-ERK1/2 protein levels were examined in the hippocampus of all mice from Experiment 3 and HT22 cells from Experiment 4., Results: METH-treated mice showed significantly worsened NOR and MWM performance, along with markably hippocampal apoptosis. A significantly lower cell survival rate was observed in METH-treated HT22 cells. Increased levels of H3R protein were found in both METH-treated mice and HT22 cells. THIO significantly improved METH-induced cognitive impairment in mice and toxicity in HT22 cells. METH significantly increased the level of p-MEK1/2 and p-ERK1/2 proteins in the hippocampus of mice and HT22 cells, which was reversed by THIO pretreatment., Conclusion: Our findings reveal that H3R blockade by THIO yields a neuroprotective effect against METH-induced cognitive impairment in mice and toxicity in HT22 cells via the raf-MEK-ERK signaling pathway., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Acetaminophen (APAP) overdose induces acute liver injury (ALI), even acute liver failure (ALF). There is a significant unmet need to furtherly elucidate the mechanisms and find new therapeutic target. Recently, emerging evidence indicates that nicotinamide adenine dinucleotide (NAD + ) plays a crucial role in APAP-induced ALI. Herein, we firstly investigated the protein expression of NAD kinase (NADK), as the rate-limiting enzyme converting NAD + to nicotinamide adenine dinucleotide phosphate (NADP + ), and found it was positively correlated with APAP-induced ALI in a dose- and time-dependent manner. Additionally, supplementation of N-acetylcysteine (NAC), known as an antidote of APAP, mitigated the ALI and downregulated the expression of NADK which was also in a dose-dependent manner. Moreover, pretreatment with methotrexate (MTX), the inhibitor of NADK, attenuated the levels of transaminases, alleviated morphological abnormalities, and improved oxidative stress triggered by APAP overdose, which was attributed to elevated hepatic NAD + pool. Subsequently, the increased NAD + upregulated the expression of Sirt1, SOD2 and attenuated DNA damage. Collectively, elevated expression of NADK is related to APAP-induced ALI, and inhibition of NADK alleviates the ALI through elevating liver NAD + level and improving antioxidant capacity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Many models were established to estimate gross primary production (GPP) of terrestrial ecosystems based on vegetation light use efficiency (LUE). Analysing the spatial-temporal variations of global terrestrial GPP became capable with the increasing length of satellite data. Previous studies mainly focused on evaluating the model performance or investigating the mean, the temporal trend or the interannual variability (IAV) of global terrestrial GPP based on one single or multiple models, which is difficult to identify common merits of a same cluster of GPP models. This study compared eight satellite-based LEU-type GPP models in capturing the mean, temporal trend and IAV of global GPP concurrently. Our results showed that current common-used models based on LUE methodology estimated global mean GPP ranging from 128.5 to 158.3 Pg C year -1 , and global mean IAV ranging from 0.1 to 0.35, but the trends ranging from -0.22 to 0.51 Pg C year -1 . In the context of plant functional types (PFTs) and climate classifications, no consistent feature for either of the mean, trend or IAV of GPP are identified among eight models. Future studies should integrate the latest advances on the mechanisms and associated environmental factors into models and consolidate performance of models to better understand the evolutions of terrestrial ecosystem functioning., Competing Interests: Declaration of competing interest All the coauthors have agreed with the contents of this manuscript to be submitted to STOTEN. No part of the research has been published or submitted in any form elsewhere while this manuscript is being considered for publication in STOTEN. The authors declare no competing interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: To determine and compare retinal capillaries damage in patients with chronic central serous chorioretinopathy (CSC) after half-dose and half-time photodynamic therapy (PDT) based on optical coherence tomographic angiography (OCTA)., Methods: Thirty-three eyes of 33 patients and 32 eyes of 32 patients with active CSC were treated with half-dose PDT and half-time PDT respectively and followed up for 3 months. Fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) were performed at baseline; best corrected visual acuity (BCVA) and OCTA were performed at baseline, 3-day, 7-day, 14-day, 1-month, and 3-month follow-up visits., Results: Twenty-eight patients in half-dose group and 27 patients in the half-time group finished the 3-month follow-up visits. BCVA was significantly improved at post-PDT 1 month and 3 months (both P < 0.05) and central macula thickness (CMT) was significantly decreased at all post-PDT time points (all P < 0.05) in both groups. 22 patients (78.57%) in the half-dose group and 21 patients (77.78%) in the half-time group had complete absorption of subretinal fluid (SRF) at post-PDT 3 months. There was no significant difference in the above-mentioned prognostic measurements between two groups. The mean vessel densities of superficial retina (VDSR) and inner retina (VDIR) layers were decreased at all post-PDT time points in both groups. However, the decrease of VDIR and VDSR at post-PDT 3 days and 3 months in the half-dose group was much severe than those in the half-time group (P < 0.05)., Conclusions: Both half-dose and half-time modifications of PDT were similarly effective in improving the BCVA and decreasing the SRF for chronic CSC. However, the retinal capillaries damage in the half-time group was less severe than that in the half-dose group, so the half-time modification may be a more appropriate parameter for patients with chronic CSC., (Copyright © 2021. Published by Elsevier B.V.)

Ecosystems in arid and semi-arid regions are vulnerable to climatic and anthropogenic disturbances. However, our understanding of vegetation stability (including resistance and resilience, which are the abilities of ecosystems to resist perturbations and return to pre-disturbance structure or function, respectively) in response to environmental changes in dryland ecosystems remains insufficient, particularly in the absence of large-scale observations of water availability. Here we introduced GRACE monthly total water storage anomaly (TWSA) data into an autoregressive model with remote sensed EVI, air temperature and precipitation to investigate the short-term vegetation stability and its influencing factors in Central Asia (CA) during 2003-2015. The results showed that the grid-level vegetation resilience in CA increased logarithmically as mean annual precipitation (R 2  = 0.33, P < 0.05) but decreased linearly with increasing mean annual temperature (R 2  = 0.41, P < 0.05). Vegetation resilience was not correlated with TWSA, due to the decoupling of TWSA with precipitation both spatially and temporally in the majority of CA. At the biome level, vegetation resilience also increased as a logarithmical function of aridity index (R 2  = 0.80, P < 0.05). Vegetation resistance to TWSA showed minor difference across biomes, while vegetation resistance to precipitation functioned as a parabolic curve along the aridity gradient (R 2  = 0.59, P < 0.05). Our results suggest that accounting for the effects of total water column instead of precipitation only is critical in understanding vegetation-water relationships in drylands. The steep decrease in vegetation resilience in areas with high temperature and low water availability implies a high risk of collapse for these water-limited ecosystems if there are severe droughts. Furthermore, reduction in total water storage, induced by, e.g., large-scale extraction of surface runoff or shallow-layer groundwater for irrigation, can result in negative influences to natural biomes in dryland regions., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The Earth's Critical Zone, where physical, chemical and biological systems interact, extends from the top of the canopy to the underlying bedrock. In this study, we investigated soil moisture controls on phenology and productivity of an Acacia woodland in semi-arid central Australia. Situated on an extensive sand plain with negligible runoff and drainage, the carry-over of soil moisture content (θ) in the rhizosphere enabled the delay of phenology and productivity across seasons, until conditions were favourable for transpiration of that water to prevent overheating in the canopy. Storage of soil moisture near the surface (in the top few metres) was promoted by a siliceous hardpan. Pulsed recharge of θ above the hardpan was rapid and depended upon precipitation amount: 150mm storm(-1) resulted in saturation of θ above the hardpan (i.e., formation of a temporary, discontinuous perched aquifer above the hardpan in unconsolidated soil) and immediate carbon uptake by the vegetation. During dry and inter-storm periods, we inferred the presence of hydraulic lift from soil storage above the hardpan to the surface due to (i) regular daily drawdown of θ in the reservoir that accumulates above the hardpan in the absence of drainage and evapotranspiration; (ii) the dimorphic root distribution wherein most roots were found in dry soil near the surface, but with significant root just above the hardpan; and (iii) synchronisation of phenology amongst trees and grasses in the dry season. We propose that hydraulic redistribution provides a small amount of moisture that maintains functioning of the shallow roots during long periods when the surface soil layer was dry, thereby enabling Mulga to maintain physiological activity without diminishing phenological and physiological responses to precipitation when conditions were favourable to promote canopy cooling., (Copyright © 2016 Elsevier B.V. All rights reserved.)