Abstract
Major depressive disorder ranks as a major burden of disease worldwide, yet the current antidepressant medications are limited by frequent non-responsiveness and significant side effects. ...The lateral septum (LS) is thought to control of depression, however, the cellular and circuit substrates are largely unknown. Here, we identified a subpopulation of LS GABAergic adenosine A
2A
receptors (A
2A
R)-positive neurons mediating depressive symptoms via direct projects to the lateral habenula (LHb) and the dorsomedial hypothalamus (DMH). Activation of A
2A
R in the LS augmented the spiking frequency of A
2A
R-positive neurons leading to a decreased activation of surrounding neurons and the bi-directional manipulation of LS-A
2A
R activity demonstrated that LS-A
2A
Rs are necessary and sufficient to trigger depressive phenotypes. Thus, the optogenetic modulation (stimulation or inhibition) of LS-A
2A
R-positive neuronal activity or LS-A
2A
R-positive neurons projection terminals to the LHb or DMH, phenocopied depressive behaviors. Moreover, A
2A
R are upregulated in the LS in two male mouse models of repeated stress-induced depression. This identification that aberrantly increased A
2A
R signaling in the LS is a critical upstream regulator of repeated stress-induced depressive-like behaviors provides a neurophysiological and circuit-based justification of the antidepressant potential of A
2A
R antagonists, prompting their clinical translation.
Chronic obstructive pulmonary disease (COPD) affects the whole body and causes many extrapulmonary adverse effects, amongst which diaphragm dysfunction is one of the prominent manifestations. ...Diaphragm dysfunction in patients with COPD is manifested as structural changes, such as diaphragm atrophy, single-fibre dysfunction, sarcomere injury and fibre type transformation, and functional changes such as muscle strength decline, endurance change, diaphragm fatigue, decreased diaphragm mobility, etc. Diaphragm dysfunction directly affects the respiratory efficiency of patients and is one of the important pathological mechanisms leading to progressive exacerbation of COPD and respiratory failure, which is closely related to disease mortality. At present, the possible mechanisms of diaphragm dysfunction in patients with COPD include systemic inflammation, oxidative stress, hyperinflation, chronic hypoxia and malnutrition. However, the specific mechanism of diaphragm dysfunction in COPD is still unclear, which, to some extent, increases the difficulty of treatment and rehabilitation. Therefore, on the basis of the review of changes in the structure and function of COPD diaphragm, the potential mechanism of diaphragm dysfunction in COPD was discussed, the current effective rehabilitation methods were also summarised in this paper. In order to provide direction reference and new ideas for the mechanism research and rehabilitation treatment of diaphragm dysfunction in COPD.
It has been shown that the changes in global terrestrial water storage (TWS) are strongly linked to the teleconnections (TCs) that induce large-scale climate variations. However, the contributions of ...the different TCs to global changes of TWS and its components (water storage components, WSCs) remain undetermined. To fill this gap, we systematically assess the relationships between six major ocean-related TCs and different WSCs derived from the Gravity Recovery and Climate Experiment (GRACE) mission and hydrological models under different timescales. Additionally, the interrelationships of the TCs are also analyzed via the independent component analysis for further investigation. The results allow an improved understanding of the hydrometeorological process controlling WSC changes. Specifically, the annual timescale analysis can constrain high-frequency noises and retain the informative fluctuations of WSC residuals. ENSO and AMO are found to be the two most dominant TCs controlling the variations of WSCs globally. TWS and groundwater storage (GWS) are the two WSCs most correlated with the dominant TCs. The WSCs at shallow depths, which are largely affected by strongly hysteretic controls of TCs, are more closely linked to the TCs with many high-frequency components that tend to have weak hysteresis on WSCs. As for the interrelationships of TCs, the independent component, which is highly correlated with all six TCs, has a predominant influence on WSCs.
Microbial consortia isolated from aged oil-contaminated soil were used to degrade 16 polycyclic aromatic hydrocarbons (15.72
mg
kg
−1) in soil and slurry phases. The three microbial consortia ...(bacteria, fungi and bacteria–fungi complex) could degrade polycyclic aromatic hydrocarbons (PAHs), and the highest PAH removals were found in soil and slurry inoculated with fungi (50.1% and 55.4%, respectively). PAHs biodegradation in slurry was lower than in soil for bacteria and bacteria–fungi complex inoculation treatments. Degradation of three- to five-ring PAHs treated by consortia was observed in soil and slurry, and the highest degradation of individual PAHs (anthracene, fluoranthene, and benz(a)anthracene) appeared in soil (45.9–75.5%, 62–83.7% and 64.5–84.5%, respectively) and slurry (46.0–75.8%, 50.2–86.1% and 54.3–85.7%, respectively). Therefore, inoculation of microbial consortia (bacteria, fungi and bacteria–fungi complex) isolated from in situ contaminated soil to degrade PAHs could be considered as a successful method.
Learning disabilities are hallmarks of congenital conditions caused by prenatal exposure to harmful agents. These include fetal alcohol spectrum disorders (FASDs) with a wide range of cognitive ...deficiencies, including impaired motor skill development. Although these effects have been well characterized, the molecular effects that bring about these behavioral consequences remain to be determined. We previously found that the acute molecular responses to alcohol in the embryonic brain are stochastic, varying among neural progenitor cells. However, the pathophysiological consequences stemming from these heterogeneous responses remain unknown. Here we show that acute responses to alcohol in progenitor cells altered gene expression in their descendant neurons. Among the altered genes, an increase of the calcium-activated potassium channel Kcnn2 in the motor cortex correlated with motor learning deficits in a mouse model of FASD. Pharmacologic blockade of Kcnn2 improves these learning deficits, suggesting Kcnn2 blockers as a new intervention for learning disabilities in FASD.
Proximal tubular (PT) acidosis, which alkalinizes the urinary filtrate, together with Ca2+ supersaturation in PT can induce luminal calcium phosphate (CaP) crystal formation. While such CaP crystals ...are known to act as a nidus for CaP/calcium oxalate (CaOx) mixed stone formation, the regulation of PT luminal Ca2+ concentration (Ca2+) under elevated pH and/or high Ca2+ conditions are unknown. Since we found that transient receptor potential canonical 3 (TRPC3) knockout (KO; -/-) mice could produce mild hypercalciuria with CaP urine crystals, we alkalinized the tubular pH in TRPC3-/- mice by oral acetazolamide (0.08%) to develop mixed urinary crystals akin to clinical signs of calcium nephrolithiasis (CaNL). Our ratiometric (λ340/380) intracellular Ca2+ measurements reveal that such alkalization not only upsurges Ca2+ influx into PT cells, but the mode of Ca2+ entry switches from receptor-operated to store-operated pathway. Electrophysiological experiments show enhanced bicarbonate related current activity in treated PT cells which may determine the stone-forming phenotypes (CaP or CaP/CaOx). Moreover, such alkalization promotes reactive oxygen species generation, and upregulation of calcification, inflammation, fibrosis, and apoptosis in PT cells, which were exacerbated in absence of TRPC3. Altogether, the pH-induced alteration of the Ca2+ signaling signature in PT cells from TRPC3 ablated mice exacerbated the pathophysiology of mixed urinary stone formation, which may aid in uncovering the downstream mechanism of CaNL.
Objectives:
Peripheral skeletal muscle dysfunction is an important extrapulmonary manifestation of chronic obstructive pulmonary disease (COPD) that can be counteracted by exercise training. This ...study aimed to review the effect of three major exercise training modalities, which are used in pulmonary rehabilitation to improve on skeletal muscle mass, function, and exercise capacity in COPD.
Methods:
PubMed, Embase, EBSCO, Web of Science, and the PEDro database were searched on April 25, 2020. Only randomized controlled studies published in English evaluating the effects of exercise interventions on peripheral skeletal muscle mass, strength, and exercise capacity in stable COPD patients were included. The quality of included studies was evaluated using the PEDro scale. The mean difference (MD) or the standardized mean difference (SMD) with 95% CI was calculated to summarize the results. Subgroup meta-analysis was used to investigate the effects of different exercise training modalities and different outcome measures. The Grading of Recommendations Assessment, Development, and Evaluation guidelines were used to rate evidence quality.
Results:
A total of 30 randomized controlled trials involving 1,317 participants were included. Data from trials investigating endurance exercise (EE), resistance exercise (RE), and combined aerobic and resistance exercise (CE) were pooled into a meta-analysis, and the differences compared with the non-exercising COPD control were improvement in the muscle strength and exercise capacity in stable COPD patients. Subgroup meta-analysis for different exercise training modalities showed that RE significantly improved muscle strength (SMD = 0.6, 95% CI 0.35–0.84,
I
2
= 61%), EE and CE significantly increased VO
2peak
(EE: MD = 3.5, 95% CI 1.1–5.91,
I
2
= 92%; CE: MD = 1.66, 95% CI 0.22–3.1,
I
2
= 1%). Subgroup meta-analysis for different outcome measures showed that only isotonic strength was improved after exercise interventions (SMD = 0.89, 95% CI 0.51–1.26,
I
2
= 71%).
Conclusion:
Moderate evidence supports that exercise training in stable COPD patients has meaningful and beneficial effects on peripheral skeletal muscle strength and exercise capacity. Peripheral skeletal muscle shows a higher response to RE, and the isotonic test is relatively sensitive in reflecting muscle strength changes. The proportion of aerobic and resistance exercise components in a combined exercise program still needs exploration.
Systematic Review Registration:
The review was registered with the PROSPERO: (The website is
https://www.crd.york.ac.uk/PROSPERO/
, and the ID is CRD42020164868).
North China Plain (NCP), China, a semi-arid region with intense groundwater withdrawals.
This paper developed a framework using meteorological data, model-simulated terrestrial water storage ...anomalies (TWSA), and additional in-situ (groundwater level, GL) data to improve the unsatisfactory GRACE-TWSA reconstruction in arid and semi-arid regions due to the intense anthropogenic influence on groundwater. The inconsistency between point-scale data (GL) and grid-scale data (GRACE-TWSA and predictors other than GL) is handled by feature extraction techniques. Moreover, to deal with temporal non-stationarity, the time series are separated into trend and detrended components, the patterns of which are further learned by linear and nonlinear machine learning models, respectively.
New hydrological insights for the region: Multi-site GL observations in NCP can not only serve as validation data but also as predictors providing invaluable information on human effects for the reconstructed TWSA improvement (from 6.51 to 3.86 cm for Root Mean Square Error and from 0.56 to 0.82 for Nash-Sutcliffe Efficiency). Our results show that multi-site GL data in NCP are highly inter-correlated and can be represented by several principal components, demonstrating the strong hydraulic connectivity in NCP. We also find a significant one-month lag and linear relationship between the trends of GRACE-TWSA and GL changes in NCP. These deeper understandings of hydrologic processes have implications for enhancing the GRACE-TWSA estimations in other similar regions.
Display omitted
•In-situ groundwater levels are utilized to reconstruct GRACE-derived TWSA.•Spatial scale mismatch and temporal non-stationarity of data are considered.•Reconstructed TWSA with groundwater levels improves especially for the trend.•Anthropogenic influences are better exhibited in the reconstructed TWSA.
The Zhangshi Irrigation Area (ZIA) in Shenyang, China has been irrigated by industrial wastewater since 1962. Since then, parts of the ZIA have been rezoned for industrial uses, but the remaining ...area, named Sluice Gate III (SLIII) and Lower Reaches (LR), still occupies 1825
ha. Although land irrigation with industrial wastewater ceased in 1992, a study on heavy metals in soils was carried out to assess the feasibility of agricultural crop cultivation in SLIII and LR. A detailed field investigation was conducted and both total heavy metal concentrations and bioavailable fraction in soil were determined.
The results have highlighted that Cd concentrations in soils still exceed the Environmental Quality Standard for Soil in China (GB15618-1995) grade C standard in SLIII region, and grade B standard in LR. In the SLIII, Zn and Pb concentrations in soil are higher than the grade A standard, although Cu is close the grade A standard. In SLIII the dominant chemical fractions were the exchangeable and carbonatic forms, which represent up to 43% and 35% of the Cd, respectively. The Cd in these two fractionations poses the highest risk for the plant absorption and accumulation. Therefore the SLIII should be abandoned for cultivated crops to prevent the Cd contamination of food chain and any associated hazards to human health.
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