Guizhi Fuling capsule relieves memory deficits by inhibition of microglial neuroinflammation through blocking JAK2/STAT3 pathway in presenilin1/2 conditional double knockout mice.

Chronic neuroinflammation has been regarded as an important part of the pathological initiation of Alzheimer's disease (AD), which is associated with the regulation of microglial activation. Preventing microglial activation to inhibit neuroinflammation may become a potential target for the treatment of neurodegenerative diseases. Guizhi Fuling capsule (GZFL) has a strong repression on inflammatory responses. Here, the presenilin1/2 conditional double knockout (PS cDKO) mice, a well-established mouse model of AD, were divided into: WT mice (WT), WT mice+GZFL (WT+GZFL), PS cDKO mice (cDKO), and PS cDKO mice+GZFL (cDKO+GZFL). Mice in the WT+GZFL and cDKO+GZFL group were fed standard chow containing 2000 ppm GZFL for 90 days. After 60 days of GZFL treatment, mice were given to behavioral tests for 30 days in order to explore the effects of GZFL on cognitive and motor function. Then, mice were sacrificed for examining the effects of GZFL on inflammation. Furthermore, primary microglia were obtained from neonatal Sprague-Dawley rats and pretreated with or without GZFL (50 µg/ml) for 1 h in the absence or presence of lipopolysaccharide (LPS) (100 ng/ml) stimulation to speculate whether the underlying mechanism of GZFL's anti-inflammatory potential was closely associated with Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. Our findings indicated that GZFL has the ability to alleviate memory deficits in PS cDKO mice, which attributes to the improvement of neuroinflammation by inhibiting microglial activation and the levels of pro-inflammatory mediators. In addition, GZFL could inverse the tau hyperphosphorylation and the lessened expression of synaptic proteins in hippocampus of PS cDKO mice. Furthermore, GZFL prevented LPS-induced neuroinflammatory responses in primary microglia by decreasing the levels of pro-inflammatory mediators. It is noteworthy that therapeutic effects of GZFL on memory impairment are depended on the inhibition of neuroinflammatory responses by the blockage of JAK2/STAT3 signaling pathway. Taken together, GZFL may be an effective compound Chinese medicine for the improvement and postponement of neurodegenerative progression in AD.

The impact of natural fibers' characteristics on mechanical properties of the cement composites.

The paper reviews the properties of cement composites reinforced with short fibres. The effect of natural fibres was investigated: cotton, sisal, jute, ramie, bamboo, and synthetic fibres: polymer and polypropylene. It was noticed that the fibres change the consistency of the mixture up to 15%. In the composite flexural strength tests, a change in strength by +/- 8% was observed, depending on the type of fibres used. The research shows that the use of natural fibres had a positive effect on the compressive strength by 27%, while the use of synthetic fibres caused its decrease by 4%. Additionally, it was noticed that the chemical composition, the diameter and the total length of the fibres in the element have an impact on the composite shrinkage. The fibre-containing composites showed an 8% higher water absorption compared to the non-fibre samples. The exception is the ramie fibres, which reduce water absorption. In general, a positive effect of natural fibers on the properties of cement composites has been noticed, however, in case of natural fibres application, a thorough further properties investigation is recommended.

Peony seed oil ameliorates neuroinflammation-mediated cognitive deficits by suppressing microglial activation through inhibition of NF-κB pathway in presenilin 1/2 conditional double knockout mice.

Chronic neuroinflammation has been shown to exert adverse influences on the pathology of Alzheimer's disease (AD), associated with the release of abundant proinflammatory mediators by excessively activated microglia, causing synaptic dysfunction, neuronal degeneration, and memory deficits. Thus, the prevention of microglial activation-associated neuroinflammation is important target for deterring neurodegenerative disorders. Peony seed oil (PSO) is a new food resource, rich in α-linolenic acid, the precursor of long chain omega-3 polyunsaturated fatty acids, including docosahexaenoic acid and eicosapentaenoic acid, which exhibit anti-inflammatory properties by altering cell membrane phospholipid fatty acid compositions, disrupting lipid rafts, and inhibiting the activation of the proinflammatory transcription factor NF-κB. However, few studies have examined the anti-neuroinflammatory effects of PSO in AD, and the relevant molecular mechanisms remain unclear. Presenilin1/2 conditional double knockout (PS cDKO) mice display obvious AD-like phenotypes, such as neuroinflammatory responses, synaptic dysfunction, and cognitive deficits. Here, we assessed the potential neuroprotective effects of PSO against neuroinflammation-mediated cognitive deficits in PS cDKO using behavioral tests and molecular biologic analyses. Our study demonstrated that PSO suppressed microglial activation and neuroinflammation through the down-regulation of proinflammatory mediators, such as inducible NOS, COX-2, IL-1ß, and TNF-α, in the prefrontal cortex and hippocampus of PS cDKO mice. Further, PSO significantly lessened memory impairment by reversing hyperphosphorylated tau and synaptic proteins deficits in PS cDKO mice. Importantly, PSO's therapeutic effects on cognitive deficits were due to inhibiting neuroinflammatory responses mediated by NF-κB signaling pathway. Taken together, PSO may represent an effective dietary supplementation to restrain the neurodegenerative processes of AD.

Climate change may interact with nitrogen fertilizer management leading to different ammonia loss in China's croplands.

Despite research into the response of ammonia (NH3 ) volatilization in farmland to various meteorological factors, the potential impact of future climate change on NH3 volatilization is not fully understood. Based on a database consisting of 1063 observations across China, nonlinear NH3  models considering crop type, meteorological, soil and management variables were established via four machine learning methods, including support vector machine, multi-layer perceptron, gradient boosting machine and random forest (RF). The RF model had the highest R2 of 0.76 and the lowest RMSE of 0.82 kg NH3 -N ha-1 , showing the best simulation capability. Results of model importance indicated that NH3 volatilization was mainly controlled by total input of N fertilizer, followed by meteorological factors, human managements and soil characteristics. The NH3 emissions of China's cereal production (paddy rice, wheat and maize) in 2018 was estimated to be 3.3 Mt NH3 -N. By 2050, NH3 volatilization will increase by 23.1-32.0% under different climate change scenarios (Representative Concentration Pathways, RCPs), and climate change will have the greatest impact on NH3 volatilization in the Yangtze river agro-region of China due to high warming effects. However, the potential increase in NH3 volatilization under future climate change can be mitigated by 26.1-47.5% through various N fertilizer management optimization options.