The Effect of Fermentation on the Chemical Constituents of Gastrodia Tuber Hallimasch Powder (GTHP) Estimated by UHPLC-Q-Orbitrap HRMS and HPLC.

OBJECTIVE: To compare the effect of fermentation on the chemical constituents of Gastrodia Tuder Halimasch Powder (GTHP), to establish its fingerprinting and multicomponent content determination, and to provide a basis for the processing, handling, and clinical application of this herb. METHODS: Ultra-high-performance liquid chromatography-quadrupole-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) was used to conduct a preliminary analysis of the chemical constituents in GTHP before and after fermentation. High-performance liquid chromatography (HPLC) was used to determine some major differential components of GTHP and establish fingerprints. Cluster analysis (CA), and principal component analysis (PCA) were employed for comprehensive evaluation. RESULTS: Seventy-nine compounds were identified, including flavonoids, organic acids, nucleosides, terpenoids, and others. The CA and PCA results showed that ten samples were divided into three groups. Through standard control and HPLC analysis, 10 compounds were identified from 22 peaks, namely uracil, guanosine, adenosine, 5-hydroxymethylfurfural (5-HMF), daidzin, genistin, glycitein, daidzein, genistein, and ergosterol. After fermentation, GTHP exhibited significantly higher contents of uracil, guanosine, adenosine, 5-hydroxymethylfurfural, and ergosterol and significantly lower genistein and daidzein contents. CONCLUSIONS: The UHPLC-Q-Orbitrap HRMS and HPLC methods can effectively identify a variety of chemical components before and after the fermentation of GTHP. This study provides a valuable reference for further research on the rational clinical application and quality control improvement of GTHP.

Activation of σ-1 receptor mitigates estrogen withdrawal-induced anxiety/depressive-like behavior in mice via restoration of GABA/glutamate signaling and neuroplasticity in the hippocampus.

Postpartum depression (PPD) is a significant contributor to maternal morbidity and mortality. The Sigma-1 (σ-1) receptor has received increasing attention in recent years because of its ability to link different signaling systems and exert its function in the brain through chaperone actions, especially in neuropsychiatric disorders. YL-0919, a novel σ-1 receptor agonist developed by our institute, has shown antidepressive and anxiolytic effects in a variety of animal models, but effects on PPD have not been revealed. In the present study, excitatory/inhibitory signaling in the hippocampus was reflected by GABA and glutamate and their associated excitatory-inhibitory receptor proteins, the HPA axis hormones in the hippocampus were assessed by ELISA. Finally, immunofluorescence for markers of newborn neuron were undertaken in the dentate gyri, along with dendritic spine staining and dendritic arborization tracing. YL-0919 rapidly improves anxiety and depressive-like behavior in PPD-like mice within one week, along with normalizing the excitation/inhibition signaling as well as the HPA axis activity. YL-0919 rescued the decrease in hippocampal dendritic complexity and spine density induced by estrogen withdrawal. The study results suggest that YL-0919 elicits a therapeutic effect on PPD-like mice; therefore, the σ-1 receptor may be a novel promising target for PPD treatment in the future.

A review of methods for assessment of cognitive function in high-altitude hypoxic environments.

Hypoxic environments like those present at high altitudes may negatively affect brain function. Varying levels of hypoxia, whether acute or chronic, are previously shown to impair cognitive function in humans. Assessment and prevention of such cognitive impairment require detection of cognitive changes and impairment using specific cognitive function assessment tools. This paper summarizes the findings of previous research, outlines the methods for cognitive function assessment used at a high altitude, elaborates the need to develop standardized and systematic cognitive function assessment tools for high-altitude hypoxia environments.

Intermittent hypoxia training effectively protects against cognitive decline caused by acute hypoxia exposure.

Intermittent hypoxia training (IHT) is a promising approach that has been used to induce acclimatization to hypoxia and subsequently lower the risk of developing acute mountain sickness (AMS). However, the effects of IHT on cognitive and cerebrovascular function after acute hypoxia exposure have not been characterized. In the present study, we first confirmed that the simplified IHT paradigm was effective at relieving AMS at 4300 m. Second, we found that IHT improved participants' cognitive and neural alterations when they were exposed to hypoxia. Specifically, impaired working memory performance, decreased conflict control function, impaired cognitive control, and aggravated mental fatigue induced by acute hypoxia exposure were significantly alleviated in the IHT group. Furthermore, a reversal of brain swelling induced by acute hypoxia exposure was visualized in the IHT group using magnetic resonance imaging. An increase in cerebral blood flow (CBF) was observed in multiple brain regions of the IHT group after hypoxia exposure as compared with the control group. Based on these findings, the simplified IHT paradigm might facilitate hypoxia acclimatization, alleviate AMS symptoms, and increase CBF in multiple brain regions, thus ameliorating brain swelling and cognitive dysfunction.

Atmospheric HONO emissions in China: Unraveling the spatiotemporal patterns and their key influencing factors.

Nitrous acid (HONO) can be photolyzed to produce hydroxyl radicals (OH) in the atmosphere. OH plays a critical role in the formation of secondary pollutants like ozone (O3) and secondary organic aerosols (SOA) via various oxidation reactions. Despite the abundance of recent HONO studies, research on national HONO emissions in China remains relatively limited. Therefore, this study employed a "wetting-drying" model and bottom-up approach to develop a high-resolution gridded inventory of HONO emissions for mainland China using multiple data. We used the Monte Carlo method to estimate the uncertainty in HONO emissions. In addition, the primary sources of HONO emissions were identified and their spatiotemporal distribution and main influencing factors were studied. The results indicated that the total HONO emissions in mainland China in 2016 were 0.77 Tg N (R50: 0.28-1.42 Tg N), with soil (0.42 Tg N) and fertilization (0.26 Tg N) as the primary sources, jointly contributing to over 87% of the total. Notably, the North China Plain (NCP) had the highest HONO emission density (3.51 kg N/ha/yr). Seasonal HONO emissions followed the order: summer (0.38 kg N/ha) > spring (0.19 kg N/ha) > autumn (0.17 kg N/ha) > winter (0.06 kg N/ha). Moreover, HONO emissions were strongly correlated with fertilization, cropland, temperature, and precipitation. This study provides vital scientific groundwork for the atmospheric nitrogen cycle and the formation of secondary pollutants.

Rapid visual nucleic acid detection of Vibrio alginolyticus by recombinase polymerase amplification combined with CRISPR/Cas13a.

Vibrio alginolyticus (V. alginolyticus) is a common pathogen in the ocean. In addition to causing serious economic losses in aquaculture, it can also infect humans. The rapid detection of nucleic acids of V. alginolyticus with high sensitivity and specificity in the field is very important for the diagnosis and treatment of infection caused by V. alginolyticus. Here, we established a simple, fast and effective molecular method for the identification of V. alginolyticus that does not rely on expensive instruments and professionals. The method integrates recombinase polymerase amplification (RPA) technology with CRISPR system in a single PCR tube. Using this method, the results can be visualized by lateral flow dipstick (LFD) in less than 50 min, we named this method RPA-CRISPR/Cas13a-LFD. The method was confirmed to achieve high specificity for the detection of V. alginolyticus with no cross-reactivity with similar Vibrio and common clinical pathogens. This diagnostic method shows high sensitivity; the detection limit of the RPA-CRISPR/Cas13a-LFD is 10 copies/µL. We successfully identified 35 V. alginolyticus strains from a total of 55 different bacterial isolates and confirmed their identity by (Matrix-assisted laser desorption ionization time-of-flight mass spectrometry, MALDI-TOF MS). We also applied this method on infected mice blood, and the results were both easily and rapidly obtained. In conclusion, RPA-CRISPR/Cas13a-LFD offers great potential as a useful tool for reliable and rapid diagnosis of V. alginolyticus infection, especially in limited conditions.

Gas Chromatographic-Ion Mobility Spectrometry Combined with Chemometrics to Study the Changes in Characteristic Odor Components of Galli gigerii Endothelium Corneum in Different Processing Methods.

Galli gigerii endothelium corneum (GGEC) is a traditional Chinese medicine commonly used in clinical practice to treat various conditions such as indigestion, vomiting, spermatorrhea, and enuresis. In this study, the volatile components of different concoctions of GGEC were examined by gas chromatography-ion mobility spectrometry (GC-IMS), and the changes of the components were compared by fingerprinting, combined with principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) to analyze the main volatile components and find out the different markers that can distinguish the different concoctions of GGEC. In the result, the GC-IMS fingerprints of GGEC and its different concoctions showed differences in their volatile components, of which 49 volatiles were clearly characterized, with some components including monomers and dimers. The characteristic volatile components of raw GGEC (SP) were n-nonanal, (E)-2-octenal, beta-ocimene, 2-ethyl-1-hexanol, etc. The characteristic volatile components of stir-fried GGEC (QC) are heptanal, 2-octanol, (E)-2-heptenal, etc. The characteristic volatile components of sand ironing GGEC (ST) are isoamyl acetate, decanal, cyclohexanone, 2-ethyl pyrazine, etc. The characteristic volatile components of stir-fried GGEC with vinegar (CZ) are thiazole, linalool, 2,3,5-trimethylpyrazine, etc. The characteristic volatile components of stir-fried GGEC with milk (FH) are 2-methylbutanoic acid, ethyl acetate, ethyl 2-hydroxypropanoate, butyl acetate, etc. By chemometric analysis, components such as n-nonanal, (E)-2-octenal, 2-pentyl-furan, butanal, 1,4-dioxane, and 2-methylpropanoic acid could be used as difference markers to distinguish different concoction products of GGEC. Furthermore, by analyzing different volatile compounds, we can examine the changes in volatile components during processing of GGEC, which can provide experimental data for the identification and establishment of quality standards.

Improved ammonia emission inventory of fertilizer application for three major crops in China based on phenological data.

NH3 has an important impact on atmospheric chemistry, and its reduction has become a potential pathway to alleviate haze pollution. The existing NH3 emission inventories still have significant uncertainties in terms of their temporal distributions. In this study, we combined satellite remote-sensing phenological data with ground-station phenological data to develop a method for the temporal allocation of NH3 emissions from fertilizer application. A high-resolution dataset for fertilizer application in China was established. We developed NH3 emission inventories for the fertilization of three major crops in China, with a resolution of 1/12° × 1/12°. The results showed that there was a significant temporal variation in fertilizer application dates across the country, mainly concentrated in June (17.16 %), July (19.08 %), and August (18.77 %). The majority of fertilizer application for the three major crops occurred during the spring and summer months, with a particular emphasis on April (5.72 Tg), May (7.05 Tg), and June (4.29 Tg). The total NH3 emission from the three major crops in China in 2019 was 2.73 Tg. The North China Plain (762.23 Gg) and Middle and Lower Yangtze River Plain (606.85 Gg) were identified as the primary regions for high NH3 emissions from fertilizer application. The results also showed that NH3 emissions from the three major crops were predominantly observed during summer, with a peak value in July (606.99 Gg), mainly because of the high proportion of topdressing fertilizers. Areas with high fertilizer application generally coincided with areas of high NH3 emissions. This study may be the first to utilize remote-sensing phenological data to establish the NH3 emission inventory, which is of great significance for further improving the accuracy of the NH3 emission inventory.

A Novel Sample-to-Answer Visual Nucleic Acid Detection System for Adenovirus Detection.

Human adenoviruses (HAdVs) are common viruses that can cause local outbreaks in schools, communities and military camps, posing a huge threat to public health. An ideal POCT device for adenovirus detection in resource-limited settings is critical to control the spread of the virus. In this study, we developed an integrated and electricity-independent sample-to-answer system that can complete nucleic acid extraction, amplification, and detection at room temperature. This system is suitable for field and on-site detection because of its rapidity, sensitivity, lack of contamination, and lack of requirements of high-precision instruments and skilled technicians. It consists of two separate modules, ALP FINA (alkaline lysis with the paper-based filtration isolation of nucleic acid) and SV RPA (sealed and visual recombinase polymerase amplification). The extraction efficiency of ALP FINA can reach 48 to 84%, which is close to that of the conventional centrifuge column. The detection sensitivity of SV RPA is close to 10 copies/µL of AdvB and AdvE without aerosol contamination after repeated operations. When SV RPA was applied to the detection of nasopharyngeal swab samples of 19 patients who were infected with AdvB or AdvE as well as 10 healthy volunteers, its sensitivity and specificity reached 100%, respectively. IMPORTANCE HAdV infections are readily transmittable and, in some instances, highly contagious. Early and rapid diagnosis is essential for disease control. In this work, we developed a portable, disposable, and modularized sample-to-answer detection system for AdvB and AdvE, which rendered the entire test to be completely independent of electricity and other laboratory infrastructure. Thus, this detection system can be applied in resource-limited settings, and it has the potential to be further developed as an early diagnosis method in the field.

Atmospheric ammonia in China: Long-term spatiotemporal variation, urban-rural gradient, and influencing factors.

In recent years, atmospheric ammonia (NH3) concentrations have increased in China. Ammonia control has become one of the next hot topics in air pollution mitigation with the increasing cost of acid gas emission reduction. In this study, using Infrared Atmospheric Sounding Interferometer (IASI) satellite observations, we analyzed the spatiotemporal distribution, the urban-rural gradient of the vertical column densities (VCDs) of NH3 and the contribution of influencing factors (meteorology, social, atmospheric acid gases, and NH3 emissions) in China from 2008 to 2019 using hotspot analysis, circular gradient analysis, geographical and temporal weighted regression, and some other methods. Our results showed that NH3 VCDs in China have significantly increased (31.88 %) from 2008 to 2019, with the highest occurring in North China Plain. The average NH3 VCDs in urban areas were significantly higher than those in rural areas, and the urban-rural gap in NH3 VCDs was widening. The results of circular gradient analysis showed an overall decreasing trend in NH3 VCDs along the urban-rural gradient. We used a geographically and temporally weighted regression model to analyze the contribution of various influencing factors to NH3 VCDs: meteorology (30.13 %), social (27.40 %), atmospheric acid gases (23.20 %), and NH3 emissions (19.28 %) factors. The results showed substantial spatiotemporal differences in the influencing factors. Atmospheric acid gas was the main reason for the increase in NH3 VCDs from 2008 to 2019. A more thorough understanding of the spatiotemporal distribution, urban-rural variations, and factors influencing NH3 in China will aid in developing control strategies to reduce PM2.5.

Sigma-1 receptor agonist properties that mediate the fast-onset antidepressant effect of hypidone hydrochloride (YL-0919).

The most intriguing characteristic of the sigma-1 receptor is its ability to regulate multiple functional proteins directly via protein-protein interactions, giving the sigma-1 receptor the powerful ability to regulate several survival and metabolic functions in cells, fine tune neuronal excitability, and regulate the transmission of information within brain circuits. This characteristic makes sigma-1 receptors attractive candidates for the development of new drugs. Hypidone hydrochloride (YL-0919), a novel structured antidepressant candidate developed in our laboratory, possess a selective sigma-1 receptor agonist profile, as evidenced by molecular docking, radioligand receptor binding assays, and receptor functional experiments. In vivo studies have revealed that YL-0919 elicits a fast-onset antidepressant activity (within one week) that can be attenuated with pretreatment of the selective sigma-1 receptor antagonist, BD-1047. Taken together, the findings of the current study suggest that YL-0919 activates the sigma-1 receptor to partially mediate the rapid onset antidepressant effects of YL-0919. Thus, YL-0919 is a promising candidate as a fast-onset antidepressant that targets the sigma-1 receptor.

Autophagy Is Essential for Neural Stem Cell Proliferation Promoted by Hypoxia.

Hypoxia as a microenvironment or niche stimulates proliferation of neural stem cells (NSCs). However, the underlying mechanisms remain elusive. Autophagy is a protective mechanism by which recycled cellular components and energy are rapidly supplied to the cell under stress. Whether autophagy mediates the proliferation of NSCs under hypoxia and how hypoxia induces autophagy remain unclear. Here, we report that hypoxia facilitates embryonic NSC proliferation through HIF-1/mTORC1 signaling pathway-mediated autophagy. Initially, we found that hypoxia greatly induced autophagy in NSCs, while inhibition of autophagy severely impeded the proliferation of NSCs in hypoxia conditions. Next, we demonstrated that the hypoxia core regulator HIF-1 was necessary and sufficient for autophagy induction in NSCs. Considering that mTORC1 is a key switch that suppresses autophagy, we subsequently analyzed the effect of HIF-1 on mTORC1 activity. Our results showed that the mTORC1 activity was negatively regulated by HIF-1. Finally, we provided evidence that HIF-1 regulated mTORC1 activity via its downstream target gene BNIP3. The increased expression of BNIP3 under hypoxia enhanced autophagy activity and proliferation of NSCs, which was mediated by repressing the activity of mTORC1. We further illustrated that BNIP3 can interact with Rheb, a canonical activator of mTORC1. Thus, we suppose that the interaction of BNIP3 with Rheb reduces the regulation of Rheb toward mTORC1 activity, which relieves the suppression of mTORC1 on autophagy, thereby promoting the rapid proliferation of NSCs. Altogether, this study identified a new HIF-1/BNIP3-Rheb/mTORC1 signaling axis, which regulates the NSC proliferation under hypoxia through induction of autophagy.

Diagnostic model constructed by nine inflammation-related genes for diagnosing ischemic stroke and reflecting the condition of immune-related cells.

Background: Ischemic cerebral infarction is the most common type of stroke with high rates of mortality, disability, and recurrence. However, the known diagnostic biomarkers and therapeutic targets for ischemic stroke (IS) are limited. In the current study, we aimed to identify novel inflammation-related biomarkers for IS using machine learning analysis and to explore their relationship with the levels of immune-related cells in whole blood samples. Methods: Gene expression profiles of healthy controls and patients with IS were download from the Gene Expression Omnibus. Analysis of differentially expressed genes (DEGs) was performed in healthy controls and patients with IS. Single-sample gene set enrichment analysis was performed to calculate inflammation scores, and weighted gene co-expression network analysis was used to analyze genes in significant modules associated with inflammation scores. Key DEGs in significant modules were then analyzed using LASSO regression analysis for constructing a diagnostic model. The effectiveness and specificity of the diagnostic model was verified in healthy controls and patients with IS and with cerebral hemorrhage (CH) using qRT-PCR. The relationship between diagnostic score and the levels of immune-related cells in whole blood were analyzed using Pearson correlations. Results: A total of 831 DEGs were identified. Both chronic and acute inflammation scores were higher in patients with IS, while 54 DEGs were also clustered in the gene modules associated with chronic and acute inflammation scores. Among them, a total of 9 genes were selected to construct a diagnostic model. Interestingly, RT-qPCR showed that the diagnostic model had better diagnostic value for IS but not for CH. The levels of lymphocytes were lower in blood of patients with IS, while the levels of monocytes and neutrophils were increased. The diagnostic score of the model was negatively associated with the levels of lymphocytes and positively associated with levels of monocytes and neutrophils. Conclusions: Taken together, the diagnostic model constructed using the inflammation-related genes TNFSF10, ID1, PAQR8, OSR2, PDK4, PEX11B, TNIP1, FFAR2, and JUN exhibited high and specific diagnostic value for IS and reflected the condition of lymphocytes, monocytes, and neutrophils in the blood. The diagnostic model may contribute to the diagnosis of IS.

BNIP3 phosphorylation by JNK1/2 promotes mitophagy via enhancing its stability under hypoxia.

Mitophagy is an important metabolic mechanism that modulates mitochondrial quality and quantity by selectively removing damaged or unwanted mitochondria. BNIP3 (BCL2/adenovirus e1B 19 kDa protein interacting protein 3), a mitochondrial outer membrane protein, is a mitophagy receptor that mediates mitophagy under various stresses, particularly hypoxia, since BNIP3 is a hypoxia-responsive protein. However, the underlying mechanisms that regulate BNIP3 and thus mediate mitophagy under hypoxic conditions remain elusive. Here, we demonstrate that in hypoxia JNK1/2 (c-Jun N-terminal kinase 1/2) phosphorylates BNIP3 at Ser 60/Thr 66, which hampers proteasomal degradation of BNIP3 and drives mitophagy by facilitating the direct binding of BNIP3 to LC3 (microtubule-associated protein 1 light chain 3), while PP1/2A (protein phosphatase 1/2A) represses mitophagy by dephosphorylating BNIP3 and triggering its proteasomal degradation. These findings reveal the intrinsic mechanisms cells use to regulate mitophagy via the JNK1/2-BNIP3 pathway in response to hypoxia. Thus, the JNK1/2-BNIP3 signaling pathway strongly links mitophagy to hypoxia and may be a promising therapeutic target for hypoxia-related diseases.

Effective Absorption Mechanism of SO2 and NO2 in the Flue Gas by Ammonium-Bromide-Based Deep Eutectic Solvents.

Simultaneous capture of SO2 and NO x from flue gas is critical for coal-fired power generation. In this study, environmentally friendly and high-performance deep eutectic solvents based on ethylene glycol and ammonium bromide were designed to capture SO2 and NO2 simultaneously. The SO2 and NO2 absorption performances and absorption mechanisms were systematically investigated by 1H NMR and Fourier transform infrared (FT-IR) spectroscopy in combination with ab initio calculations using Gaussian software. The results showed that EG-TBAB DESs can absorb low concentrations of SO2 and NO2 from the flue gas simultaneously at low temperatures (≤50 °C). 1H NMR, FT-IR, and simulation results indicate that SO2 and NO2 are absorbed by forming EG-TBAB-SO2-NO2 complexes, Br- is the main active site for NO2 absorption, and NO2 is more active in an EG-TBAB-NO2-SO2 complex than SO2. EG-TBAB DESs exhibit outstanding regeneration capability, and absorption capacities remain unchanged after five absorption-desorption cycles. The fundamental understanding of simultaneous capture of SO2 and NO2 from this study enables DES structures to be rationally designed for efficient and low-cost desulfurization and denitrification reagents.

Sigma-1 Receptors in Depression: Mechanism and Therapeutic Development.

Depression is the most common type of neuropsychiatric illness and has increasingly become a major cause of disability. Unfortunately, the recent global pandemic of COVID-19 has dramatically increased the incidence of depression and has significantly increased the burden of mental health care worldwide. Since full remission of the clinical symptoms of depression has not been achieved with current treatments, there is a constant need to discover new compounds that meet the major clinical needs. Recently, the roles of sigma receptors, especially the sigma-1 receptor subtype, have attracted increasing attention as potential new targets and target-specific drugs due to their translocation property that produces a broad spectrum of biological functions. Even clinical first-line antidepressants with or without affinity for sigma-1 receptors have different pharmacological profiles. Thus, the regulatory role of sigma-1 receptors might be useful in treating these central nervous system (CNS) diseases. In addition, long-term mental stress disrupts the homeostasis in the CNS. In this review, we discuss the topical literature concerning sigma-1 receptor antidepressant mechanism of action in the regulation of intracellular proteostasis, calcium homeostasis and especially the dynamic Excitatory/Inhibitory (E/I) balance in the brain. Furthermore, based on these discoveries, we discuss sigma-1 receptor ligands with respect to their promise as targets for fast-onset action drugs in treating depression.

Preliminary Intermittent Hypoxia Training Alleviates the Damage of Sustained Normobaric Hypoxia on Human Hematological Indexes and Cerebral White Matter.

Zhang, Guangbo, Yanzhao Zhou, Zhengtao Cao, Xiang Cheng, Xiangpei Yue, Tong Zhao, Ming Zhao, Yongqi Zhao, Ming Fan, and Lingling Zhu. Preliminary intermittent hypoxia training alleviates the damage of sustained normobaric hypoxia on human hematological indexes and cerebral white matter. High Alt Med Biol. 23:273-283, 2022. Background: We aimed to examine the effects of preliminary intermittent hypoxia training (IHT) on human hematological indexes and cerebral white matter (WM) after exposure to a simulated altitude of 4,300 m. Methods: We recruited 20 young healthy volunteers. Participants were then randomized to either the IHT group (n = 10) or the control group (n = 10). We measured the physiological function of the control group at sea level and after exposure to a simulated altitude of 4,300 m, respectively. The IHT group performed the above tests at three time points: before and after hypoxia training, and after exposure to a simulated altitude of 4,300 m, respectively. Results: We found that mean SpO2 during day 10 of hypoxia training showed a significant increase compared with mean SpO2 on day 1 (88.3% ± 1.5% vs. 90.0% ± 1.6%, p < 0.05), and erythrocyte P50 of post-training was significantly increased compared with pretraining (37.8 ± 2.9 mmHg vs. 45.9 ± 6.4 mmHg, p < 0.05). Mean SpO2 measures after acute exposure to high altitude exhibited a significant difference, with the IHT group showing significantly greater SpO2 than the control group (73.8% ± 3.7% vs. 77.4% ± 3.2%, p < 0.05), and the Lake Louise Score was also lower than the control group (2.55 ± 2.1 vs. 6.67 ± 2.5, p < 0.05). After daily IHT, brain-derived neurotrophic factor plasma levels of participants in the IHT group did not change but significantly increased in response to high-altitude hypoxia (103.5% ± 70.4% vs. 29.7% ± 73.2%, p < 0.05). Interleukin-10 (IL-10) plasma level did not change before and after IHT in the IHT group, whereas the IL-10 plasma level of the control group after high-altitude exposure was significantly higher. Furthermore, we found that fractional anisotropy values in the left corticospinal tract and splenium of the corpus callosum in the IHT group were significantly higher than those in the control group after high-altitude hypoxia. Conclusions: These results demonstrate that IHT alleviates the damage of sustained normobaric hypoxia on human hematological indexes and cerebral WM.

Intermittent hypoxia treatment alleviates memory impairment in the 6-month-old APPswe/PS1dE9 mice and reduces amyloid beta accumulation and inflammation in the brain.

BACKGROUND: Alzheimer's disease (AD) is a progressive, degenerative, and terminal disease without cure. There is an urgent need for a new strategy to treat AD. The aim of this study was to investigate the effects of intermittent hypoxic treatment (IHT) on cognitive functions in a mouse model of AD and unravel the mechanism of action of IHT. METHODS: Six-month-old APPswe/PS1dE9 (APP/PS1) male mice were exposed to hypoxic environment (14.3% O2) 4 h/day for 14 days or 28 days. Cognitive functions were measured by Morris water maze test after either 14 days or 42 days of interval. Thereafter the distribution of amyloid plaque and microglial activation were determined by mouse brain immunohistochemistry, while the amyloid beta (Aß) and inflammatory cytokines were measured by ELISA and Western Blot. Microarray was used for studying gene expressions in the hippocampus. RESULTS: IHT for 14 days or 28 days significantly improved the spatial memory ability of the 6-month-old APP/PS1 mice. The memory improvement by 14 days IHT lasted to 14 days, but not to 42 days. The level of Aß plaques and neurofilament accumulations was reduced markedly after the IHT exposure. IHT reduced the pro-inflammatory cytokines IL-1ß, IL-6 levels, and ß-secretase cleavage of APP processing which implies reduced Aß production. Microarray analysis revealed a large number of genes in the hippocampus were significantly altered which are known to be metabolism-regulated genes. CONCLUSIONS: This study provides evidence of the beneficial effect of IHT on the progression of AD by alleviating memory impairment, reducing Aß accumulation and inflammation in the brain. IHT can be developed as a novel measure to relieve the progression of AD by targeting multiple pathways in the AD pathogenesis.

The Effect of Circulating Fluidised Bed Bottom Ash Content on the Mechanical Properties and Drying Shrinkage of Cement-Stabilised Soil.

This study aimed to determine the effect of circulating fluidised bed bottom ash (CFB-BA) content on the mechanical properties and drying shrinkage of cement-stabilised soil. Experiments were performed to study the changes in unconfined compressive strength and expansibility of cement-stabilised soil with different CFB-BA contents and the underlying mechanisms based on microscopic properties. The results show that CFB-BA can effectively increase the unconfined compressive strength of the specimen and reduce the amount of cement in the soil. When the combined content of CFB-BA and cement in the soil was 30%, the unconfined compressive strength of the specimen with C/CFB = 2 after 60 days of curing was 10.138 MPa, which is 1.4 times that of the pure cement specimen. However, the CFB-BA does not significantly improve the strength of the soil and cannot be added alone as a cementing material to the soil. Additionally, swelling tests showed that the addition of CFB-BA to cement-stabilised soil can significantly reduce the drying shrinkage. This research project provides reference values for the application of CFB-BA in cement-soil mixing piles, including compressive strength and the reduction in the shrinkage deformation of specimens.

A novel low-cost electrode for recording the local field potential of freely moving rat's brain.

Local field potentials (LFPs) are involved in almost all cognitive activities of animals. Several kinds of recording electrodes are used for recording LFPs in freely moving animals, including commercial and homemade electrodes. However, commercial recording electrodes are expensive, and their relatively fixed size often causes a steric hindrance effect, especially when combining deep brain stimulation (DBS) with LFP recording, which may not always satisfy the aim of researchers. Currently, an increasing number of researchers are designing their own recording electrodes to lower research costs. Nevertheless, there is no simple universal method to produce low-cost recording electrodes with a specific size according to the target brain area. Thus, we developed a simple method for quickly producing low-cost multiple-channel recording electrodes. To inspect the effectiveness of our self-designed electrode, LFPs were recorded in a Parkinson's disease (PD) rat model, and an electrical stimulation electrode was implanted into the subthalamic nucleus to verify the space-saving ability of the self-designed recording electrode. The results showed that <30 min was needed to prepare an electrode and that the electrode materials cost <5 dollars. Further investigations showed that our electrode successfully recorded the beta oscillations (12-40 Hz) in the PD rat model. Thus, this method will greatly reduce the cost of recording electrodes and save time for researchers. Additionally, the small size of the electrode will further facilitate DBS research.