Trajectory of mid-arm subcutaneous fat, muscle mass predicts mortality in hemodialysis patients independent of body mass index.

Although decreasing body mass index (BMI) is associated with higher mortality risk in patients undergoing hemodialysis (HD), BMI neither differentiates muscle and fat mass nor provides information about the variations of fat distribution. It remains unclear whether changes over time in fat and muscle mass are associated with mortality. We examined the prognostic significance of trajectory in the triceps skinfold (TSF) thickness and mid-upper arm circumference (MUAC). In this multicenter prospective cohort study, 972 outpatients (mean age, 54.5 years; 55.3% men) undergoing maintenance HD at 22 treatment centers were included. We calculated the relative change in TSF and MUAC over a 1-year period. The outcome was all-cause mortality. Kaplan-Meier, Cox proportional hazard analyses, restricted cubic splines, and Fine and Gray sub-distribution hazards models were performed to examine whether TSF and MUAC trajectories were associated with all-cause mortality. During follow-up (median, 48.0 months), 206 (21.2%) HD patients died. Compared with the lowest trajectory group, the highest trajectories of TSF and MUAC were independently associated with lower risk for all-cause mortality (HR = 0.405, 95% CI 0.257-0.640; HR = 0.537; 95% CI 0.345-0.837; respectively), even adjusting for BMI trajectory. Increasing TSF and MUAC over time, measured as continuous variables and expressed per 1-standard deviation decrease, were associated with a 55.7% (HR = 0.443, 95% CI 0.302-0.649), and 97.8% (HR = 0.022, 95% CI 0.005-0.102) decreased risk of all-cause mortality. Reduction of TSF and MUAC are independently associated with lower all-cause mortality, independent of change in BMI. Our study revealed that the trajectory of TSF thickness and MUAC provides additional prognostic information to the BMI trajectory in HD patients.

Agrin-Lrp4 pathway in hippocampal astrocytes restrains development of temporal lobe epilepsy through adenosine signaling.

BACKGROUND: Human patients often experience an episode of serious seizure activity, such as status epilepticus (SE), prior to the onset of temporal lobe epilepsy (TLE), suggesting that SE can trigger the development of epilepsy. Yet, the underlying mechanisms are not fully understood. The low-density lipoprotein receptor related protein (Lrp4), a receptor for proteoglycan-agrin, has been indicated to modulate seizure susceptibility. However, whether agrin-Lrp4 pathway also plays a role in the development of SE-induced TLE is not clear. METHODS: Lrp4f/f mice were crossed with hGFAP-Cre and Nex-Cre mice to generate brain conditional Lrp4 knockout mice (hGFAP-Lrp4-/-) and pyramidal neuron specific knockout mice (Nex-Lrp4-/-). Lrp4 was specifically knocked down in hippocampal astrocytes by injecting AAV virus carrying hGFAP-Cre into the hippocampus. The effects of agrin-Lrp4 pathway on the development of SE-induced TLE were evaluated on the chronic seizure model generated by injecting kainic acid (KA) into the amygdala. The spontaneous recurrent seizures (SRS) in mice were video monitored. RESULTS: We found that Lrp4 deletion from the brain but not from the pyramidal neurons elevated the seizure threshold and reduced SRS numbers, with no change in the stage or duration of SRS. More importantly, knockdown of Lrp4 in the hippocampal astrocytes after SE induction decreased SRS numbers. In accord, direct injection of agrin into the lateral ventricle of control mice but not mice with Lrp4 deletion in hippocampal astrocytes also increased the SRS numbers. These results indicate a promoting effect of agrin-Lrp4 signaling in hippocampal astrocytes on the development of SE-induced TLE. Last, we observed that knockdown of Lrp4 in hippocampal astrocytes increased the extracellular adenosine levels in the hippocampus 2 weeks after SE induction. Blockade of adenosine A1 receptor in the hippocampus by DPCPX after SE induction diminished the effects of Lrp4 on the development of SE-induced TLE. CONCLUSION: These results demonstrate a promoting role of agrin-Lrp4 signaling in hippocampal astrocytes in the development of SE-induced development of epilepsy through elevating adenosine levels. Targeting agrin-Lrp4 signaling may serve as a potential therapeutic intervention strategy to treat TLE.

NRG1-ErbB4 signaling in the medial amygdala controls mating motivation in adult male mice.

Motivation-driven mating is a basic affair for the maintenance of species. However, the underlying molecular mechanisms that control mating motivation are not fully understood. Here, we report that NRG1-ErbB4 signaling in the medial amygdala (MeA) is pivotal in regulating mating motivation. NRG1 expression in the MeA negatively correlates with the mating motivation levels in adult male mice. Local injection and knockdown of MeA NRG1 reduce and promote mating motivation, respectively. Consistently, knockdown of MeA ErbB4, a major receptor for NRG1, and genetic inactivation of its kinase both promote mating motivation. ErbB4 deletion decreases neuronal excitability, whereas chemogenetic manipulations of ErbB4-positive neuronal activities bidirectionally modulate mating motivation. We also identify that the effects of NRG1-ErbB4 signaling on neuronal excitability and mating motivation rely on hyperpolarization-activated cyclic nucleotide-gated channel 3. This study reveals a critical molecular mechanism for regulating mating motivation in adult male mice.

Soil respiration following Chinese fir plantation clear-cut: Comparison of two forest regeneration approaches.

In response to ecological problems originating from long-term pure coniferous plantations, clear-cut, species mixing, and other forest regeneration practices have been proposed to develop into mixed conifer-broadleaved stand. However, the dynamic effects of these forest regeneration approaches on soil respiration have not been well investigated. In this study, we compared soil respiration for three continuous years from two completely different forest regeneration approaches in clear-cut areas with uncut as control in pure Chinese fir plantations in subtropical China. These two approaches were, I: ground vegetation cut and removal of slash in the first year followed by the second year's ground vegetation cut but retained on the site, and II: ground vegetation cut and slash burning in first year followed by second year's soil ploughing, replanting, ground vegetation cut but retained on the site. Soil respiration changed obviously as forest practices were applied in the both regeneration sites. Mean respiration rate for the first year was lower for the treatments of Approach I and Approach II than uncut control (-15.0% and -26.8%), indicating that soil respiration decreased with ground vegetation removal or slash burning after clear-cut. In contrast to the first year, mean respiration rate was higher for the treatments of Approach I and Approach II treatments than uncut control (+12.8% and +32.2% in the second year, 16.3% and 30.8% in the third year), indicating ground vegetation cut with retaining residuals or soil ploughing significantly increased soil respiration. These drastically changes were mainly due to the rapid growth of understory vegetation and new seedlings, the difference of species composition, the availability of respired organic matter and the intensity of soil disturbance induced by different specific forest practices of two regeneration approaches over time. In addition, the different species mixing and forest management practices enhance the uncertainty linked to the analyses of soil respiration. Our results suggest that high intensity forest regeneration approach has a higher soil CO2 emission and lower production of biomass. Forest regeneration approaches could decrease the temperature sensitivity of soil respiration. Our findings provide new insights into the effects of forest practices on soil CO2 flux following clear-cut.

Effects of forest regeneration practices on the flux of soil CO2 after clear-cutting in subtropical China.

Reforestation after clear-cutting is used to facilitate rapid establishment of new stands. However, reforestation may cause additional soil disturbance by affecting soil temperature and moisture, thus potentially influencing soil respiration. Our aim was to compare the effects of different reforestation methods on soil CO2 flux after clear-cutting in a Chinese fir plantation in subtropical China: uncut (UC), clear-cut followed by coppicing regeneration without soil preparation (CC), clear-cut followed by coppicing regeneration and reforestation with soil preparation, tending in pits and replanting (CCRP), and clear-cut followed by coppicing regeneration and reforestation with overall soil preparation, tending and replanting (CCRO). Clear-cutting significantly increased the mean soil temperature and decreased the mean soil moisture. Compared to UC, CO2 fluxes were 19.19, 37.49 and 55.93 mg m-2 h-1 higher in CC, CCRP and CCRO, respectively (P < 0.05). Differences in CO2 fluxes were mainly attributed to changes in soil temperature, litter mass and the mixing of organic matter with mineral soil. The results suggest that, when compared to coppicing regeneration, reforestation practices result in additional CO2 released, and that regarding the CO2 emissions, soil preparation and tending in pits is a better choice than overall soil preparation and tending.