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Introduction Physical activity is recommended for healthy pregnant women. Clinical practice guidelines vary with regard to initial time, duration, or type of physical activity that is recommended, which is confusing for health care professionals and pregnant women alike. This study aimed to appraise clinical guidelines relevant to physical activity for pregnant women and summarize consensus and discrepant recommendations. Methods The websites of organizations that develop guidelines including those of obstetricians, gynecologists, midwives, and medical sports associations were searched in addition to 9 literature databases for the period from January 2010 through November 2020. Guidelines were included if they were published in a journal or on a website in English or Chinese; were labeled as a recommendation guideline, position paper, practice parameter, or consensus statement; and addressed physical activity for pregnant women. Two authors independently extracted recommendations. Four reviewers independently assessed guideline quality using the AGREE II instrument. Results Thirteen guidelines met the inclusion criteria. The guidelines developed by the World Health Organization and the National Institute for Health and Clinical Excellence were deemed to have the highest methodological quality. The recommendations were consistent with regard to recommended exercise duration, frequency, intensity, and type of physical activity. The main discrepant recommendations included best tools for conducting pre-exercise screening and assessing intensity of exertion. Guidelines also differ on optimal heart rate during exercise, when in pregnancy to initiate an exercise regimen, and duration or frequency of strengthening exercises. Discussion Of the 13 guidelines, 2 were found to have good methodological quality. The recommendations that were consistent across the differing guidelines can support health care providers in counseling women about physical activity during pregnancy. The recommendations that are discrepant among these guidelines may contribute to confusion and a reluctance to recommend exercise during pregnancy. Research is needed to clarify discrepant recommendations.

More than 25% of chemical transformations involve at least one hydrogenation step. Selective hydrogenation of unsaturated aldehydes is an essential process in the industrial production of pesticide...

Formate dehydrogenase (FDH) is regarded as a universal stress protein involved in various plant abiotic stress responses. This study aims to ascertain GmFDH function in conferring tolerance to Al stress. The bioinformatics analysis demonstrates that GmFDH from Tamba black soybean (TBS) encodes FDH. Quantitative reverse transcription-PCR (qRT-PCR) showed that GmFDH expression was induced by Al stress with a concentration-time specific pattern. Moreover, Al stress promotes formate content and activates FDH activity. Further studies revealed that GmFDH overexpression alleviated root growth inhibition and reduced Al and ROS accumulation in roots. In addition, transgenic tobaccos had much more root citrate exudation and much higher activity of antioxidant enzymes than wild type. Interestingly, although the expression of NtMATE and NtALS3 was not significantly different under Al stress between transgenic tobaccos and wild type, citrate synthase activity is higher in transgenic tobaccos than that of wild type, which might be the reason for citrate secretion increase. Overall, these results indicate that GmFDH overexpression alleviates Al toxicity by enhancing activities of antioxidant enzymes and promoting citrate secretion.

Major depressive disorder (MDD) is a prevalent and devastating mental illness. To date, the diagnosis of MDD is largely dependent on clinical interviews and questionnaires and still lacks a reliable biomarker. DNA methylation has a stable and reversible nature and is likely associated with the course and therapeutic efficacy of complex diseases, which may play an important role in the etiology of a disease. Here, we identified and validated a DNA methylation biomarker for MDD from four independent cohorts of the Chinese Han population. First, we integrated the analysis of the DNA methylation microarray (

Major depressive disorder (MDD) is a prevalent and devastating mental illness. To date, the diagnosis of MDD is largely dependent on clinical interviews and questionnaires and still lacks a reliable biomarker. DNA methylation has a stable and reversible nature and is likely associated with the course and therapeutic efficacy of complex diseases, which may play an important role in the etiology of a disease. Here, we identified and validated a DNA methylation biomarker for MDD from four independent cohorts of the Chinese Han population. First, we integrated the analysis of the DNA methylation microarray ( n = 80) and RNA expression microarray data ( n = 40) and identified BICD2 as the top-ranked gene. In the replication phase, we employed the Sequenom MassARRAY method to confirm the DNA hypermethylation change in a large sample size ( n = 1,346) and used the methylation-sensitive restriction enzymes and a quantitative PCR approach (MSE-qPCR) and qPCR method to confirm the correlation between DNA hypermethylation and mRNA down-regulation of BICD2 ( n = 60). The results were replicated in the peripheral blood of mice with depressive-like behaviors, while in the hippocampus of mice, Bicd2 showed DNA hypomethylation and mRNA/protein up-regulation. Hippocampal Bicd2 knockdown demonstrates antidepressant action in the chronic unpredictable mild stress (CUMS) mouse model of depression, which may be mediated by increased BDNF expression. Our study identified a potential DNA methylation biomarker and investigated its functional implications, which could be exploited to improve the diagnosis and treatment of MDD.

The aluminum tolerance of Tamba black soybean (Glycine max cv. Tamba) is closely related to organic acid secretion mechanisms. The gene responsible for this tolerance in this variety (GmFER84) is extracted from lysates of soybean root tips using silylated Fe3O4 nanomagnetic beads. GmFER84 (Glycine max XP 003540203.1) is a stable protein. Tobacco genetically transformed with GmFER84 using an Agrobacterium-mediated transformation was tested for aluminum tolerance. Citrate synthase and citric acid secretion in the roots of transgenic tobacco prove to be significantly higher than those of wild tobacco, and the antioxidant properties of transgenic tobacco are also substantially increased. Research on GmFER84 may enable further agronomic development.

Background Telomeres are nucleoprotein complexes located at the end of chromosomes. Previous studies have confirmed that telomere length is reduced in the peripheral blood of depression patients. However, studies regarding whether telomere length is altered in brain regions associated with depression are limited. It remains unclear whether the peripheral blood telomere length indicates telomere variation in the brain. Methods Using quantitative PCR, we measured telomere length in five brain regions (prefrontal cortex, amygdala, nucleus accumbens, paraventricular nucleus, and hippocampus) from depressive-like mice and in peripheral blood from depressive-like mice and major depressive disorder (MDD) patients. We also examined the expression of telomerase- and alternative lengthening of telomere (ALT)-related genes in the prefrontal cortex and amygdala of depressive-like mice. Results Telomeres were shortened in the peripheral blood of depressive-like mice and MDD patients, but were elongated in the prefrontal cortex and amygdala compared with healthy controls. We also observed that the expression of ALT-related genes increased in the prefrontal cortex and amygdala. Limitations The amount of human sample was limited. The mechanism of telomere lengthening in the brain of depressive-like mice was not well explained. Mice and humans have inherently different telomere and telomere maintenance systems. Conclusion These findings illustrate that the telomere length in the peripheral blood may not indicate the dynamics of telomere length in the brain. They offer a new perspective on variable telomere length in different brain regions affected in depression and provide a new basis for understanding the relationship between variable telomere length and MDD.

Post-transcriptional modifications of RNA, such as RNA methylation, can epigenetically regulate behavior, for instance learning and memory. However, it is unclear whether RNA methylation plays a critical role in the pathophysiology of major depression disorder (MDD). Here, we report that expression of the fat mass and obesity associated gene (FTO), an RNA demethylase, is downregulated in the hippocampus of patients with MDD and mouse models of depression. Suppressing Fto expression in the mouse hippocampus results in depression-like behaviors in adult mice, whereas overexpression of FTO expression leads to rescue of the depression-like phenotype. Epitranscriptomic profiling of N6-methyladenosine (m6A) RNA methylation in the hippocampus of Fto knockdown (KD), Fto knockout (cKO), and FTO-overexpressing (OE) mice allows us to identify adrenoceptor beta 2 (Adrb2) mRNA as a target of FTO. ADRB2 stimulation rescues the depression-like behaviors in mice and spine loss induced by hippocampal Fto deficiency, possibly via the modulation of hippocampal SIRT1 expression by c-MYC. Our findings suggest that FTO is a regulator of a mechanism underlying depression-like behavior in mice., Post-transcriptional modification of RNA can contribute to regulating behavior. Here, the authors show that modulating the expression of Fto results in epitranscriptomic changes in the mouse hippocampus associated with depression-like behavior.

A preparative supercritical fluid chromatography method for the separation of Piper kadsura obtained five phenylamide compounds, which had the same structural skeleton, but changed in the number and position of methoxyl substituents. To improve the separation selectivity of these structural analogues, silica, phenyl, and chiral stationary phases were screened. Only through the combination of Chiral C and phenyl columns could the separation of the five phenylamides be solved. The two-step strategy using preparative supercritical fluid chromatography presented good orthogonality that ensured the purity of the phenylamides. Then, an ultra-high-performance supercritical fluid chromatography hyphened tandem mass spectrometry method was developed, and the fragmentation pattern of phenylamides was summarized. It mainly cleaved in the amide bond to produce the fragment ion, which could help to judge the substituent positions. Twenty-eight possible molecular weights of hydroxyl and methoxyl substituted phenylamides were calculated and screened. Nine compounds were extracted in three [M + H]+ ions at m/z 284.13, 314.13, and 344.13, including five purified compounds and the other four positional or trans-cis phenylamide isomers in low content. The methods developed in this research were useful in the separation and characterization of phenylamide analogues.

Moods and metabolism modulate each other. High comorbidity of depression and metabolic disorders such as diabetes and obesity poses a great challenge to treat such condition. Here we report the therapeutic efficacy of brain-derived neurotrophic factor (BDNF) by gene transfer in the dorsal raphe nucleus (DRN) in a chronic unpredictable mild stress model of depression (CUMS) and models of diabetes and obesity. In CUMS, BDNF-expressing mice displayed antidepressant- and anxiolytic-like behaviors, which are associated with augmented serotonergic activity. Both in the diet-induced obesity model (DIO) and in db/db mice，BDNF ameliorated obesity and diabetes, which may be mediated by enhanced sympathetic activity, not involving DRN serotonin. Chronic activation of DRN neurons via chemogenetic tools produced similar effects as BDNF in DIO mice. These results established the DRN as a key nexus in regulating depression-like behaviors and metabolism, which can be exploited to combat comorbid depression and metabolic disorders via BDNF gene transfer.

Glucose is the main circulating energy substrate for the adult brain. Owing to the high energy demand of nerve cells, glucose is actively oxidized to produce ATP and has a synergistic effect with mitochondria in metabolic pathways. The dysfunction of glucose metabolism inevitably disturbs the normal functioning of neurons, which is widely observed in neurodegenerative disease. Understanding the mechanisms of metabolic adaptation during disease progression has become a major focus of research, and interventions in these processes may relieve the neurons from degenerative stress. In this review, we highlight evidence of mitochondrial dysfunction, decreased glucose uptake, and diminished glucose metabolism in different neurodegeneration models such as Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD). We also discuss how hypoxia, a metabolic reprogramming strategy linked to glucose metabolism in tumor cells and normal brain cells, and summarize the evidence for hypoxia as a putative therapy for general neurodegenerative disease.

Objective A meta-analysis to investigate the risk factors for postoperative hypocalcaemia after thyroidectomy in adult patients. Methods A systematic search of publications in the electronic databases (PubMed®, The Cochrane Library, Web of Science, OVID and Embase®) from inception to June 2020 was conducted. Screening of titles, abstracts and full texts and data extraction were independently performed by two authors. The OR was selected as the pooled estimate. Results The analysis included 23 studies. Twelve significant risk factors for postoperative hypocalcaemia were identified: hypoparathyroidism, OR 5.58; total thyroidectomy, OR 3.59; hypomagnesaemia, OR 2.85; preoperative vitamin D deficiency, OR 2.32; female sex, OR 1.49; thyroid malignancy, OR 1.85; thyroiditis, OR 1.48; substernal multinodular goitres, OR 1.70; parathyroidectomy, OR 1.58; central compartment neck dissection, OR 1.17; modified radical neck dissection, OR 1.57; and central neck dissection, OR 1.54. Conclusions This meta-analysis provides moderate-to-high quality evidence that the 12 risk factors were predictive of postoperative hypocalcaemia, which should be monitored closely before thyroidectomy.

Dynamic and reversible RNA methylation has emerged as a new layer of epigenetic regulation of behaviors such as learning and memory; however, whether RNA methylation plays a critical role in the pathophysiology of depression is unclear. Here, we report that expression of the fat mass and obesity associated gene (FTO), a primary RNA demethylase, is downregulated in the hippocampi of both major depressive disorder (MDD) patients and mouse models of depression. Suppressing Fto expression in the hippocampus induces depression-like behaviors in mice, while elevating its expression leads to antidepressant effects. Epitranscriptomic profiling of N6-methyladenosine (m6A) RNA methylation in the hippocampi of Fto knockdown (KD), Fto knockout (cKO), and Fto-overexpressing (OE) mice identified adrenoceptor beta 2 (Adrb2) mRNA as a target of Fto. Adrb2 stimulation reverses the depression-like behaviors and spine loss induced by hippocampal Fto deficiency, possibly via the modulation of hippocampal Sirt1 expression by c-Myc. These findings reveal that Fto in the hippocampus mediates depression-like behaviors and highlight the importance of reversible RNA methylation in driving depression.

Aluminum (Al) toxicity is a major environmental stress that inhibits plant growth and development. There has been impressive progress in recent years that has greatly increased our understanding of the nature of Al toxicity and its mechanisms of tolerance. This review describes the transcription factors (TFs) and plant hormones involved in the adaptation to Al stress. In particular, it discusses strategies to confer plant resistance to Al stress, such as transgenic breeding, as well as small molecules and plant growth-promoting rhizobacteria (PGPRs) to alleviate Al toxicity. This paper provides a theoretical basis for the enhancement of plant production in acidic soils.

Supplemental material, sj-pdf-2-imr-10.1177_0300060521996911 for Risk factors for postoperative hypocalcaemia after thyroidectomy: A systematic review and meta-analysis by Zhimei Chen, Qiyuan Zhao, Jinlei Du, Ya Wang, Rongrong Han, Caijuan Xu, Xiaofang Chen and Min Shu in Journal of International Medical Research

Supplemental material, sj-pdf-1-imr-10.1177_0300060521996911 for Risk factors for postoperative hypocalcaemia after thyroidectomy: A systematic review and meta-analysis by Zhimei Chen, Qiyuan Zhao, Jinlei Du, Ya Wang, Rongrong Han, Caijuan Xu, Xiaofang Chen and Min Shu in Journal of International Medical Research

Ischemic stroke initiated by transient or permanent cerebral blood flow decline remains the leading cause of permanent disability in industrialized nations. Therapeutic strategies to improve patient recovery are remain limited. Hypoxia post-conditioning (HPostC) has been known to be neuroprotective against ischemic injuries in vivo and in vitro. Understanding its mechanism of action may promote its clinical translation. In this study, we devised a method of HPostC treatment to provide protection from a focal cerebral ischemic induced injury and to explore the underling mechanism. We found that our HPostC method improved energy supply by elevating the level of glucose, pyruvate and ATP/ADP ratio within the cerebral hemisphere in mice. In the distal middle cerebral artery occlusion (dMCAO) mice, this HPostC treatment reduced infarct size, and was associated with increased levels of pyruvate, pyruvate/lactate ratio and ATP/ADP ratio. Western blot analysis indicated that the HPostC treatment up-regulated AMPK signaling activities in the cerebral hemisphere. Our results suggest that this HPostC treatment exerts its neuroprotective effect by promoting glycolysis to elevate the ATP/ADP level, and the AMPK/PFKFB3 signaling pathway. These findings may provide biomarkers for clinical use of HPostC methods.

In this paper, a new concept of local wave vector is used to describe the spatial propagation characteristics of sound field at this location. Through the analysis of the local wave vector of the sound field, it can be concluded that the local wave vector of the traveling wave field points to the propagation direction of the traveling wave, and its modulus is a constant, while the local wave vector of the reverberation field has no fixed propagation direction and its modulus is not constant. This characteristic of local wave vector can be used to judge whether traveling wave field exists in sound field or not. The simulation results show that the detection performance of the local wave vector variance detector is better than that of the traditional maximum likelihood detector, orthogonal receiver. The data processing results of the tank experiment show that the existence of traveling wave field can be effectively judged by calculating the local wave vector and the target echo signal can be detected under strong reverberation condition by using the local wave vector variance detector.

Aluminum (Al) toxicity in acid soil is a worldwide agricultural problem that inhibits crop growth and productivity. However, the signal pathways associated with Al tolerance in plants remain largely unclear. In this study, tandem mass tag (TMT)-based quantitative proteomic methods were used to identify the differentially expressed plasma membrane (PM) proteins in Tamba black soybean (TBS) root tips under Al stress. Data are available via ProteomeXchange with identifier PXD017160. In addition, parallel reaction monitoring (PRM) was used to verify the protein quantitative data. The results showed that 907 PM proteins were identified in Al-treated plants. Among them, compared to untreated plants, 90 proteins were differentially expressed (DEPs) with 46 up-regulated and 44 down-regulated (fold change > 1.3 or < 0.77, p < 0.05). Functional enrichment based on GO, KEGG and protein domain revealed that the DEPs were associated with membrane trafficking and transporters, modifying cell wall composition, defense response and signal transduction. In conclusion, our results highlight the involvement of GmMATE13, GmMATE75, GmMATE87 and H+-ATPase in Al-induced citrate secretion in PM of TBS roots, and ABC transporters and Ca2+ have been implicated in internal detoxification and signaling of Al, respectively. Importantly, our data provides six receptor-like protein kinases (RLKs) as candidate proteins for further investigating Al signal transmembrane mechanisms.

Faithful representation of sound envelopes in primary auditory cortex (A1) is vital for temporal processing and perception of natural sounds. However, the emergence of cortical temporal processing mechanisms during development remains poorly understood. Although cortical inhibition has been proposed to play an important role in this process, direct in-vivo evidence has been lacking. Using loose-patch recordings in rat A1 immediately after hearing onset, we found that stimulus-following ability in fast-spiking neurons was significantly better than in regular-spiking (RS) neurons. In-vivo whole-cell recordings of RS neurons revealed that inhibition in the developing A1 demonstrated much weaker adaptation to repetitive stimuli than in adult A1. Furthermore, inhibitory synaptic inputs were of longer duration than observed in vitro and in adults. Early in development, overlap of the prolonged inhibition evoked by 2 closely following stimuli disrupted the classical temporal sequence between excitation and inhibition, resulting in slower following capacity. During maturation, inhibitory duration gradually shortened accompanied by an improving temporal following ability of RS neurons. Both inhibitory duration and stimulus-following ability demonstrated exposure-based plasticity. These results demonstrate the role of inhibition in setting the pace for experience-dependent maturation of temporal processing in the auditory cortex.

Stylo has a great potential for Al3+ resistance in acidic soils through secretion of citrate from the roots. To get insight into the molecular mechanisms responsible, transcriptomic changes were investigated in the roots after treatment with T01 (−Al3+, pH6.0), T02 (−Al3+, pH4.3) and T03 (50 µM AlCl3, pH4.3). In total, 83,197 unigenes generated from 130,933 contigs were obtained. Of them, 282, 148 and 816 differentially expressed unigenes (DEGs) were revealed in T01_vs_T02, T02_vs_T03 and T01_vs_T03 comparison, respectively (FDR 2FC > 2). DEGs by Al3+ were related to G-proteins, diacyglycerol and inositol metabolism, calcium-signaling, transcription regulation, protein modification and transporters for detoxification of Al3+. Additionally, Al3+ facilitates citrate synthesis via modifying gene expression of pathways responsible for citrate metabolism. Overall, Al3+ resistance in stylo involves multiple strategies and enhancement of citrate anabolism. The Al3+ signal transmits through heterotrimeric G-proteins, phospholipase C, inositol triphosphate, diacylglycerol, Ca2+ and protein kinases, thereby activating transcription and anion channels in plasma membrane, and resulting in citrate secretion from stylo roots.

Step-increasing directional solidification experiments are used to reveal the microstructural evolution of the degenerate pattern in Al-4.5 wt% Cu. It is found that the degenerate pattern could remain stable for abrupt growth velocity increases from 15 µm/s to 100 µm/s and the texture dimensionless intensity of the degenerate structure remains unchanged. A strong dependence of the tip-splitting spacing (λ) and frequency (ƒ) of the degenerate pattern on growth velocity was observed and fitted to the power law as λ = 134.4 × V−0.46 and ƒ = 0.005 × V1.45, suggesting that degenerate pattern growth is diffusion-limited and its tip-splitting instability dynamics are related to the Mullins-Sekerka (M-S) instability. Further characterization by electron backscattered diffraction (EBSD) analysis showed the transition from the degenerate pattern to tilted dendrites can prevail through an orientation deviation in the solidification direction.

Diabetes is a systemic disease that can cause brain damage such as synaptic impairments in the hippocampus, which is partly because of neuroinflammation induced by hyperglycemia. Brain-derived neurotrophic factor (BDNF) is essential in modulating neuroplasticity. Its role in anti-inflammation in diabetes is largely unknown. In the present study, we investigated the effects of BDNF overexpression on reducing neuroinflammation and the underlying mechanism in mice with type 1 diabetes induced by streptozotocin (STZ). Animals were stereotactically microinjected in the hippocampus with recombinant adeno-associated virus (AAV) expressing BDNF or EGFP. After virus infection, four groups of mice, the EGFP+STZ, BDNF+STZ, EGFP Control and BDNF Control groups, received STZ or vehicle treatment as indicated. Three weeks later brain tissues were collected. We found that BDNF overexpression in the hippocampus significantly rescued STZ-induced decreases in mRNA and protein expression of two synaptic plasticity markers, spinophilin and synaptophysin. More interestingly, BDNF inhibited hyperglycemia-induced microglial activation and reduced elevated levels of inflammatory factors (TNF-α, IL-6). BDNF blocked the increase in HMGB1 levels and specifically, in levels of one of the HMGB1 receptors, RAGE. Downstream of HMGB1/RAGE, the increase in the protein level of phosphorylated NF-κB was also reversed by BDNF in STZ-treated mice. These results show that BDNF overexpression reduces neuroinflammation in the hippocampus of type 1 diabetic mice and suggest that the HMGB1/RAGE/NF-κB signaling pathway may contribute to alleviation of neuroinflammation by BDNF in diabetic mice.

Current evidence shows great promise for stem cell transplantation as a new therapeutic strategy for stroke. However, stem cell transplantation for stroke is still in its infancy, with many issues that need to be addressed in order to achieve the full potential of stem cell therapy for stroke. Among the major hurdles for successful clinical translation is determining the therapeutic time window, stem cell type selection, delivery route, and underlying cellular and molecular mechanisms. In this chapter, we attempt to review the basic knowledge of pathophysiology and summarize the different stem cells for stroke treatment.

Background and purpose We tested the hypothesis that limb remote ischemic conditioning (LRIC) treatment promotes arteriogenesis and increases Notch signaling activity during stroke recovery. Methods Adult male Sprague Dawley rats were subjected to middle cerebral artery occlusion (MCAO). LRIC was applied after the onset of focal ischemia (per-conditioning), followed by repeated short episodes of remote ischemia 24 h after reperfusion (post-conditioning). Cerebral blood flow (CBF) was measured by Laser Doppler Flowmetry. Immunohistochemistry was used to reveal α-smooth muscle actin (α-SMA) immunopositive cells in the arteries of the brain. The cerebral angioarchitecture was visualized with a latex perfusion technique. Results LRIC treatment significantly elevated local cerebral blood flow and increased arteriogenesis as indicated by increased arterial diameter and vascular smooth muscle cell proliferation in the ischemic brain. The increased arteriogenesis significantly correlated with the functional outcome after stroke. Furthermore, LRIC treatment upregulated the expressions of Notch1 and Notch intracellular domain (NICD) in arteries surrounding the ischemic area. Conclusion These results suggest that the therapeutic effects of LRIC may involve the promotion of arteriogenesis during the recovery phase after focal cerebral ischemia and that Notch1 signaling seems to be an important player in limb remote ischemia-mediated arteriogenesis.

Intracranial and extracranial arterial stenosis, the primary cause of chronic cerebral hypoperfusion (CCH), is a critical reason for the pathogenesis of vascular dementia and Alzheimer's disease characterized by cognitive impairments. Our previous study demonstrated that limb remote ischemic conditioning (LRIC) improved cerebral perfusion in intracranial arterial stenosis patients. The current study aimed to test whether LRIC promotes angiogenesis and increases phosphorylated endothelial nitric oxide synthase (p-eNOS) activity in CCH rat model. Adult male Sprague-Dawley rats were randomly assigned to three different groups: sham group, bilateral carotid artery occlusion (2VO) group and 2VO+LRIC group. Cerebral Blood Flow (CBF) was measured with laser speckle contrast imager at 4 weeks. Cognitive testing was performed at four and six weeks after 2VO surgery. We demonstrated that LRIC treatment increased cerebral perfusion and improved the CCH induced spatial learning and memory impairment. Immunohistochemistry confirmed that LRIC prevented cell death in the CA1 region, and increased the number of vessels and angiogenesis in the hippocampus after 2VO. Western blot analysis shows that LRIC therapy significantly increased p-eNOS expression in the hippocampus when compared with 2VO rats. Moreover, eNOS inhibitor reduced the effect of LRIC on angiogenesis in the hippocampus and spatial learning and memory function. Our data suggested that LRIC promoted angiogenesis, which is mediated, in part, by eNOS/NO.

Hibernation is a unique physiological state that evolved to survive periods of food shortages. It is characterized by profound decreases in metabolic rate, body temperature and physiological functions. Studies have shown that animals in hibernation can resist neurological damage. Here, we aimed to study whether hypoxia can induce a hibernation-like state in a traditionally non-hibernating animal and whether it is neuroprotective. All procedures were conducted according to international guidelines on laboratory animal safety. Mice C57BL/6 (19-21g) were placed into a 125 mL jar with fresh air and the jar was sealed with a rubber plug. For each run, the tolerance limit was judged by the animals’ appearance for "air hunger”. The animal was removed from the jar as soon as its first gasping breath appeared and was moved to another fresh-air-containing jar of similar volume. This procedure was performed in four runs. The hypoxia exposure significantly decreased oxygen (O2) consumption, carbon dioxide (CO2) production, respiratory rate and heart rate. Meanwhile, rectal temperature reached a minimum of 12.7±2.56°C, which is lower than a wide range of ambient temperatures. The mimicked hibernation decreased the infarct size in a focal cerebral ischemia mouse model. Our findings suggest the possibility of inducing suspended animation-like hibernation states for medical applications post injury.

To study the change of synaptic onset latency and threshold in primary auditory cortex (A1) during the development of SD rat.Extracellular recording was used to locate A1, followed by transferred to loose-patch and whole-cell patch in vivo to record the spike activity, synaptic onset latency and threshold responses respectively. Rats were divided into 4 groups according to ages, postnatal 12-15 days, 16-18 days, 19-24 days and adult (3 months).1. The onset latency of local field potential in A1 of adult rats[(10-20)ms] was shorter than young rats[(20-30)ms]. 2. During development, the onset latency of spikes of a single neuron in response to white noise pulses decreased. And the latency in young rats P12-15 [(40.15 ± 2.67) ms] and P16-18 [(33.86 ± 4.61) ms] were longer than in adults [(22.93 ± 2.94) ms] (ANOVA-test, t = 4.330 and 1.995, P = 0.00 and 0.04) . However, the onset latencies of P19-24 [(24.80 ± 3.63) ms] and adult had no significant difference (P0.05). 3.Synaptic onset latencies of both excitation and inhibition were significantly longer in P12-15[ (38.94 ± 1.90) ms, (35.26 ± 2.40) ms] and P16-18[ (32.68 ± 2.52) ms, (30.24 ± 2.18) ms] than in adults [(19.4 ± 1.06) ms, (18.91 ± 0.77) ms] excitation (t = 6.255 and 4.662, P0.01) inhibition (t = 8.918 and 4.820, P0.01) showed significant difference. Whereas the onset latencies of P19-24[ (23.67 ± 2.46) ms, (21.43 ± 1.80) ms] and adults displayed no prominent difference(P0.01). Meanwhile, the difference between the onset latencies of excitation and inhibition became narrower during development[ (3.15 ± 1.02) ms, (2.01 ± 0.73) ms, (1.79 ± 0.85) ms, (0.39 ± 0.48) ms]. P12-15 had notably difference in comparison to adults (t = 1.739, P0.01). 4. The thresholds of synaptic response were notably higher in P12-15 (40.0 ± 1.6) dB and P16-18 (41.3 ± 11.6) dB when compared with adults (30.9 ± 0.6) dB (t = 5.284 and 5.867, P0.01) . While that of P19-24 (35.0 ± 32.7) dB showed no distinct difference (P0.01).Single neuron spiking activity, synaptic onset latency and threshold evoked by sound stimulus gradually mature during the development in rat A1.

Limb Remote ischemic conditioning (LRIC) has been proved to be a promising neuroprotective method in white matter lesions after ischemia; however, its mechanism underlying protection after chronic cerebral hypoperfusion remains largely unknown. Here, we investigated whether LRIC promoted myelin growth by activating PI3K/Akt/mTOR signal pathway in a rat chronic hypoperfusion model. Thirty adult male Sprague Dawley underwent permanent double carotid artery (2VO), and limb remote ischemic conditioning was applied for 3 days after the 2VO surgery. Cognitive function, oligodendrocyte counts, myelin density, apoptosis and proliferation activity, as well as PTEN/Akt/mTOR signaling activity were determined 4 weeks after treatment. We found that LRIC significantly inhibited oligodendrocytes apoptosis (p0.05). Western blot analysis indicated that LRIC upregulated PTEN/Akt/mTOR signaling activities in corpus callosum (p