Artificial Layer Construction via Cosolvent Enables Stable Ni-Rich Cathodes for Enhanced Lithium Storage.

Ni-rich cathodes have recently gained significant attention as next-generation cathodes for lithium-ion batteries. However, their relatively high oxidative surface should be reduced to control the high surface reactivity because the capacity retention decreases rapidly in the batteries. Herein, a simple and effective method to pretreat LiNi0.8Mn0.1Co0.1O2 (NMC811) particles using a cosolvent for improving the battery performance is reported. Imitating the interfacial reaction in practical cells, an artificial layer is created via a spontaneous redox reaction between the cathode and the organic solvent. The artificial layer comprises metal-organic compounds with reduced transition-metal cations. Benefiting from the artificial layer, the cells deliver high capacity retention at a high current density and better rate capability, which might result from the low and stable interfacial resistance of the modified NMC811 cathode. Our approach can effectively reduce the high oxidative surface of most oxide cathode materials and induce a long cyclic lifespan and high capacity retention in most battery systems.

Corrigendum: The effects of intermittent theta burst stimulation of the unilateral cerebellar hemisphere on swallowing-related brain regions in healthy subjects.

[This corrects the article DOI: 10.3389/fnhum.2023.1100320.].

The effects of intermittent theta burst stimulation of the unilateral cerebellar hemisphere on swallowing-related brain regions in healthy subjects.

Objective: We aimed to investigate the effects and mechanisms of swallowing-related brain regions using resting-state functional magnetic resonance imaging (rs-fMRI) in healthy subjects who underwent intermittent theta burst stimulation (iTBS) on dominant or non-dominant cerebellar hemispheres. Methods: Thirty-nine healthy subjects were randomized into three groups that completed different iTBS protocols (dominant cerebellum group, non-dominant cerebellum group and sham group). Before iTBS, the resting motor threshold (rMT) was measured by single-pulse transcranial magnetic stimulation (sTMS) on the cerebellar representation of the suprahyoid muscles, and the dominant cerebellar hemisphere for swallowing was determined. Forty-eight hours after elution, iTBS protocols were completed: in the dominant cerebellum group, iTBS was administered to the dominant cerebellar hemisphere, and the non-dominant cerebellar hemisphere was given sham stimulation; in the non-dominant cerebellum group, iTBS was administered to the non-dominant cerebellar hemisphere, and sham stimulation was delivered to the dominant cerebellar hemisphere; in the sham group, sham stimulation was applied to the cerebellum bilaterally. Rs-fMRI was performed before and after iTBS stimulation to observe changes in the fractional amplitude of low-frequency fluctuation (fALFF) in the whole brain. Results: Compared with baseline, the dominant cerebellum group showed increased fALFF in the ipsilateral cerebellum, and decreased fALFF in the ipsilateral middle temporal gyrus and contralateral precuneus after iTBS; the iTBS of the non-dominant cerebellum group induced increased fALFF in the ipsilateral superior frontal gyrus, the calcarine fissure and the surrounding cortex, and the contralateral inferior parietal lobule; and in the sham group, there was no significant difference in fALFF. Exploring the effects induced by iTBS among groups, the dominant cerebellum group showed decreased fALFF in the contralateral calcarine fissure, and surrounding cortex compared with the sham group. Conclusion: Intermittent theta burst stimulation of the dominant cerebellar hemisphere for swallowing excited the ipsilateral cerebellum, and stimulation of the non-dominant cerebellar hemisphere increased the spontaneous neural activity of multiple cerebrocortical areas related to swallowing. In conclusion, regardless of which side of the cerebellum is stimulated, iTBS can facilitate part of the brain neural network related to swallowing. Our findings provide supporting evidence that cerebellar iTBS can be used as a potential method to modulate human swallowing movement.

Whole-transcriptome analyses identify key differentially expressed mRNAs, lncRNAs, and miRNAs associated with male sterility in watermelon.

Male sterility is a valuable trait for watermelon breeding, as watermelon hybrids exhibit obvious heterosis. However, the underlying regulatory mechanism is still largely unknown, especially regarding the related non-coding genes. In the present study, approximately 1035 differentially expressed genes (DEGs), as well as 80 DE-lncRNAs and 10 DE-miRNAs, were identified, with the overwhelming majority down-regulated in male-sterile floral buds. Enrichment analyses revealed that the general phenylpropanoid pathway as well as its related metabolisms was predicted to be altered in a mutant compared to its fertile progenitor. Meanwhile, the conserved genetic pathway DYT1-TDF1-AMS-MS188-MS1, as well as the causal gene ClAMT1 for the male-sterile mutant Se18, was substantially disrupted during male reproductive development. In addition, some targets of the key regulators AMS and MS188 in tapetum development were also down-regulated at a transcriptional level, such as ABCG26 (Cla004479), ACOS5 (Cla022956), CYP703A2 (Cla021151), PKSA (Cla021099), and TKPR1 (Cla002563). Considering lncRNAs may act as functional endogenous target mimics of miRNAs, competitive endogenous RNA networks were subsequently constructed, with the most complex one containing three DE-miRNAs, two DE-lncRNAs, and 21 DEGs. Collectively, these findings not only contribute to a better understanding of genetic regulatory networks underlying male sterility in watermelon, but also provide valuable candidates for future research.

The HD-ZIP Gene Family in Watermelon: Genome-Wide Identification and Expression Analysis under Abiotic Stresses.

Homeodomain-leucine zipper (HD-ZIP) transcription factors are one of the plant-specific gene families involved in plant growth and response to adverse environmental conditions. However, little information is available on the HD-ZIP gene family in watermelon. In this study, forty ClHDZs were systemically identified in the watermelon genome, which were subsequently divided into four distinctive subfamilies (I-IV) based on the phylogenetic topology. HD-ZIP members in the same subfamily generally shared similar gene structures and conserved motifs. Syntenic analyses revealed that segmental duplications mainly contributed to the expansion of the watermelon HD-ZIP family, especially in subfamilies I and IV. HD-ZIP III was considered the most conserved subfamily during the evolutionary history. Moreover, expression profiling together with stress-related cis-elements in the promoter region unfolded the divergent transcriptional accumulation patterns under abiotic stresses. The majority (13/23) of ClHDZs in subfamilies I and II were downregulated under the drought condition, e.g., ClHDZ4, ClHDZ13, ClHDZ18, ClHDZ19, ClHDZ20, and ClHDZ35. On the contrary, most HD-ZIP genes were induced by cold and salt stimuli with few exceptions, such as ClHDZ3 and ClHDZ23 under cold stress and ClHDZ14 and ClHDZ15 under the salt condition. Notably, the gene ClHDZ14 was predominantly downregulated by three stresses whereas ClHDZ1 was upregulated, suggesting their possible core roles in response to these abiotic stimuli. Collectively, our findings provide promising candidates for the further genetic improvement of abiotic stress tolerance in watermelon.

High-Frequency Cerebellar rTMS Improves the Swallowing Function of Patients with Dysphagia after Brainstem Stroke.

Objective: To explore the efficacy of high-frequency repetitive transcranial magnetic stimulation (rTMS) of the swallowing motor area of the cerebellum in patients with dysphagia after brainstem stroke. Methods: A total of 36 patients with dysphagia after brainstem stroke were recruited and divided into 3 groups. Before stimulation, single-pulse transcranial magnetic stimulation (TMS) was used to determine the swallowing dominant cerebellar hemisphere and the representation of the mylohyoid muscle. The three groups of patients received bilateral cerebellar sham stimulation, dominant cerebellar rTMS + contralateral sham stimulation, or bilateral cerebellar rTMS. The stimulus plan for each side was 10 Hz, 80% resting movement threshold (rMT), 250 pulses, 1 s per stimulus, and 9 s intervals. Sham rTMS was performed with the coil held at 90° to the scalp. The changes in the motor evoked potential (MEP) amplitude and the clinical swallowing function scales of the patients after stimulation were compared among the three groups. Results: 34 patients were finally included for statistical analysis. The scores of penetration aspiration scale (PAS) and functional dysphagia scale (FDS) of the patients after 2 weeks of rTMS in the unilateral stimulation group and bilateral stimulation group were better than that in the sham stimulation group, and there was no significant difference between the two groups. The increase in the MEP amplitude of the cerebral hemisphere in the bilateral stimulation group was higher than that in the other two groups, and the increase in the MEP amplitude in the unilateral stimulation group was higher than that in sham stimulation group. There was no correlation between the improvement in patients' clinical swallowing function (PAS scores and FDS scores) and the increase in MEP amplitude in either the unilateral stimulation group or the bilateral stimulation group. Conclusion: High-frequency rTMS in the cerebellum can improve swallowing function in PSD patients and increase the excitability of the representation of swallowing in the bilateral cerebral hemispheres. Compared with unilateral cerebellar rTMS, bilateral stimulation increased the excitability of the cerebral swallowing cortex more significantly, but there was no significant difference in clinical swallowing function.

Molybdenum Oxynitride Atomic Nanoclusters Bonded in Nanosheets of N-Doped Carbon Hierarchical Microspheres for Efficient Sodium Storage.

Transition metal nitrides have attracted considerable attention as great potential anode materials due to their excellent metallic conductivity and high theoretical specific capacity. However, their cycling performance is impeded by their instability caused by the reaction mechanism. Herein, we report the engineering and synthesis of a novel hybrid architecture composed of MoO2.0N0.5 atomic nanoclusters bonded in nanosheets of N-doped carbon hierarchical hollow microspheres (MoO2.0N0.5/NC) as an anode material for sodium-ion batteries. The facile self-templating strategy for the synthesis of MoO2.0N0.5/NC involves chemical polymerization and subsequent one-step calcination treatments. The design is beneficial to improve the electrochemical kinetics, buffer the volume variation of electrodes during cycling, and provide more interfacial active sites for sodium uptake. Due to these unique structural and compositional merits, these MoO2.0N0.5/NC exhibits excellent sodium storage performance in terms of superior rate capability and stable long cycle life. The work shows a feasible and effective way to design novel host candidates and solve the long-term cycling stability issues for sodium-ion batteries.

Study on Low-Frequency Repetitive Transcranial Magnetic Stimulation Improves Speech Function and Mechanism in Patients With Non-fluent Aphasia After Stroke.

Objective: To explore the therapeutic effect and mechanism of low-frequency repetitive transcranial magnetic stimulation on the speech function of patients with non-fluent aphasia after stroke. Methods: According to the inclusion and exclusion criteria, 60 patients with post-stroke non-fluent aphasia were included and randomly divided into treatment group (rTMS group) and sham stimulation group (S-rTMS group). Patients in rTMS group were given low-frequency rTMS + ST training. Patients in the S-rTMS group were given sham low-frequency rTMS + ST training. Once a day, 5 days a week, for a total of 4 weeks. The Western Aphasia Battery and the short-form Token test were used to evaluate the language function of the patients in the two groups before and after treatment. Part of the enrolled patients were subjected to functional magnetic resonance imaging examination, and the morning fasting venous blood of the enrolled patients was drawn before and after treatment to determine the content of BDNF and TNF-α. Results: In the comparison before and after treatment within the group, all dimensions of the WAB scale of the patients in the rTMS group increased significantly. Only two dimensions of the WAB scale of the patients in the S-rTMS group improved significantly after treatment. The results of the short-form Token test showed that patients in the rTMS group improved significantly before and after treatment. The resting state functional magnetic resonance imaging of the two groups of patients before and after treatment showed: the activation of multiple brain regions in the left hemisphere of the rTMS group increased compared with the control group. The serum BDNF content of the patients in the rTMS group was significantly higher than that of the patients in the S-rTMS group after treatment. Conclusion: Low-frequency rTMS combined with conventional speech training can significantly improve the speech function of patients with non-fluent aphasia after stroke.

The Effect of Repetitive Transcranial Magnetic Stimulation of Cerebellar Swallowing Cortex on Brain Neural Activities: A Resting-State fMRI Study.

Objective: The effects and possible mechanisms of cerebellar high-frequency repetitive transcranial magnetic stimulation (rTMS) on swallowing-related neural networks were studied using resting-state functional magnetic resonance imaging (rs-fMRI). Method: A total of 23 healthy volunteers were recruited, and 19 healthy volunteers were finally included for the statistical analysis. Before stimulation, the cerebellar hemisphere dominant for swallowing was determined by the single-pulse TMS. The cerebellar representation of the suprahyoid muscles of this hemisphere was selected as the target for stimulation with 10 Hz rTMS, 100% resting motor threshold (rMT), and 250 pulses, with every 1 s of stimulation followed by an interval of 9 s. The motor evoked potential (MEP) amplitude of the suprahyoid muscles in the bilateral cerebral cortex was measured before and after stimulation to evaluate the cortical excitability. Forty-eight hours after elution, rTMS was reapplied on the dominant cerebellar representation of the suprahyoid muscles with the same stimulation parameters. Rs-fMRI was performed before and after stimulation to observe the changes in amplitude of low-frequency fluctuation (ALFF) and regional homology (ReHo) at 0.01-0.08 Hz, 0.01-0.027 Hz, and 0.027-0.073 Hz. Results: After cerebellar high-frequency rTMS, MEP recorded from swallowing-related bilateral cerebral cortex was increased. The results of rs-fMRI showed that at 0.01-0.08 Hz, ALFF was increased at the pons, right cerebellum, and medulla and decreased at the left temporal lobe, and ReHo was decreased at the left insular lobe, right temporal lobe, and corpus callosum. At 0.01-0.027 Hz, ALFF was decreased at the left temporal lobe, and ReHo was decreased at the right temporal lobe, left putamen, and left supplementary motor area. Conclusion: Repetitive transcranial magnetic stimulation of the swallowing cortex in the dominant cerebellar hemisphere increased the bilateral cerebral swallowing cortex excitability and enhanced pontine, bulbar, and cerebellar spontaneous neural activity, suggesting that unilateral high-frequency stimulation of the cerebellum can excite both brainstem and cortical swallowing centers. These findings all provide favorable support for the application of cerebellar rTMS in the clinical practice.

Candidate gene analysis of watermelon stripe pattern locus ClSP ongoing recombination suppression.

KEY MESSAGE: Using two segregating population, watermelon stripe pattern underlying gene ClSP was delimited to a 611.78 Kb region, consisting of four discrete haploblocks and ongoing recombination suppression. Stripe pattern is an important commodity trait in watermelon, displaying diverse types. In this study, two segregating populations were generated for genetic mapping the single dominant locus ClSP, which was finally delimited to a 611.78 Kb interval with suppression of recombination. According to polymorphism sites detected among genotypes, four discrete haploblocks were characterized in this target region. Based on reference genomes, 81 predicted genes were annotated in the ClSP interval, including seven transcription factors namely as candidate No1-No7. Meanwhile, the ortholog gene of cucumber ist responsible for the irregular stripes was considered as candidate No8. Strikingly, gene structures of No1-No5 completely varied from their reference descriptions and subsequently re-annotated. For instance, the original adjacent distribution candidates No2 and No3 were re-annotated as No2_3, while No4 and No5 were integrated as No4_5. Sequence analysis demonstrated the third polymorphism in CDS of re-annotated No4_5 resulting in truncated proteins in non-stripe plants. Furthermore, only No4_5 was down-regulated in light green stripes relative to dark green stripes. Transcriptome analysis identified 356 DEGs between dark green striped and light green striped peels, with genes involved in photosynthesis and chloroplast development down-regulated in light green stripes but calcium ion binding related genes up-regulated. Additionally, 38 DEGs were annotated as transcription factors, with the majority up-regulated in light green stripes, such as ERFs and WRKYs. This study not only contributes to a better understanding of the molecular mechanisms underlying watermelon stripe development, but also provides new insights into the genomic structure of ClSP locus and valuable candidates.

Hepatic Oxidative Stress, Apoptosis, and Inflammation in Broiler Chickens With Wooden Breast Myopathy.

Wooden breast (WB) syndrome has emerged as a global myopathy in modern commercial broiler chickens, mainly affecting the pectoralis major muscle. Recent evidence suggests that WB myopathy is a systemic disease, which might be accompanied by other physiological disparities and metabolic changes. This study was conducted to systemically investigate the potential physiological changes in liver tissues as well as the possible mechanisms involved to enhance the understanding of the etiology. A total of 93 market-age Arbor Acres male broiler chickens were sampled and categorized into control (CON) and WB groups based on the evaluation of myopathic lesions. Liver samples were collected (n = 10 in each group) for histopathological evaluation and biochemical analyses. Results indicated that WB birds exhibited significantly higher plasma aspartate amino transferase, alkaline phosphatase, and gamma glutamyl transpeptidase activities. Histopathological changes in hydropic/fatty degeneration, inflammatory cell infiltration, intrahepatic hemorrhages, elevated myeloperoxidase activity, and overproduction of nitric oxide were observed in WB liver compared with CON, suggesting the occurrence of liver injury in birds affected by WB myopathy. The WB group showed increased levels of reactive oxygen species, oxidative products, as well as enhanced antioxidant capacities in the liver. These changes were associated with impaired mitochondria morphology and mitochondrial dysfunction. WB myopathy also induced mitochondria-mediated hepatic apoptosis by upregulating levels of caspases 3 and 9, altering the expressions of apoptotic B-cell lymphoma-2 family regulators, as well as increasing the release of cytochrome c. The activation of nuclear factor kappa-light-chain-enhancer of activated B cell signaling enhanced the mRNA expression of downstream inflammatory mediators, contributing to the production of inflammatory cytokines in WB liver. Combined, these findings suggest that hepatic disorders may be conjoined with WB myopathy in broiler chickens and indicating systemic physiological disparities, and other metabolic changes accompanying this myopathy need further assessment.

Physical exercise modulates the astrocytes polarization, promotes myelin debris clearance and remyelination in chronic cerebral hypoperfusion rats.

AIMS: White matter damage is the main pathological feature of chronic cerebral hypoperfusion (CCH) and glial activation is crucial in this process. Physical exercise has protective effects on CCH, but the mechanism is unclear. Therefore, this study focuses on investigating the influence of physical exercise on activated astrocytes polarization and its role in CCH. MAIN METHODS: Rats were given wheel running 48 h after 2VO (2 vessel occlusion) surgery. The cognitive function was evaluated by Morris water maze and novel object recognition test. Inflammatory cytokines expressions were detected by ELISA. Astrocytes polarization was analyzed by immunofluorescence. Myelin debris clearance and remyelination were detected by immunofluorescence and transmission electron microscopy. KEY FINDINGS: Astrocytes were activated and mainly switched to A1 phenotype in rats 2 and 3 months after 2VO. Myelin debris deposition and limited remyelination can be observed at the corresponding time. Whereas physical exercise can improve the cognitive function of 2VO rats, downregulate the expression of inflammatory factors IL-1α, C1q and TNF, upregulate the release of TGFß, and promote activated astrocytes transformation from A1 to A2 phenotype. In addition, it can also enhance myelin debris removal and remyelination. SIGNIFICANCE: These findings suggest that the benefits of physical exercise on white matter repair and cognition improvement may be related to its regulation of astrocytes polarization, which contributes to myelin debris clearance and effective remyelination in CCH.

The impaired redox status and activated nuclear factor-erythroid 2-related factor 2/antioxidant response element pathway in wooden breast myopathy in broiler chickens.

OBJECTIVE: Wooden breast (WB) is a novel myopathy affecting modern broiler chickens, which causes substantial economic losses in the poultry industry. The objective of this study was to evaluate the effect of WB abnormality on meat quality, redox status, as well as the expression of genes of the nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway. METHODS: A total of 80 broilers (Ross 308, 42 days of age, about 2.6 kg body weight) raised at Jiujin farm (Suqian, Jiangsu, China) were used. Twelve unaffected (no detectable hardness of the breast area) and twelve WB-affected (diffuse remarkable hardness in the breast muscle) birds were selected from the commercial broiler farm according to the criteria proposed by previous studies. RESULTS: The results indicated that WB showed histological lesions characterized by fiber degeneration and fibrosis, along with an increase of muscle fiber diameter (p<0.05). Moreover, higher pH value, lightness, yellowness, drip loss and cooking loss were observed in the WB group (p<0.05). Compared with the normal breast (NOR) group, the WB group showed higher formation of reactive oxygen species (p<0.05), increased level of oxidation products and antioxidant activities (p<0.05), accompanied with mitochondrial damages and lower mitochondrial membrane potential (p<0.05). Meanwhile, the relative mRNA expressions of Nrf2 and its downstream antioxidant genes including heme oxygenase-1, NAD(P)H qui none dehydrogenase 1, glutathione peroxidase, superoxide dismutase, and glutamate-cysteine ligase were higher than those of the NOR group (p<0.05). CONCLUSION: In conclusion, WB myopathy impairs meat quality by causing oxidative damages and mitochondrial dysfunction in broilers, even though the activated Nrf2/antioxidant response element pathway provides protection for the birds.

Transition Metal and Nitrogen Co-Doped Carbon-based Electrocatalysts for the Oxygen Reduction Reaction: From Active Site Insights to the Rational Design of Precursors and Structures.

Considering the urgent requirement for clean and sustainable energy, fuel cells and metal-air batteries have emerged as promising energy storage and conversion devices to alleviate the worldwide energy challenges. The key step in accelerating the sluggish oxygen reduction reaction (ORR) kinetics at the cathode is to develop cost-effective and high-efficiency non-precious metal catalysts, which can be used to replace expensive Pt-based catalysts. Recently, the transition metal and nitrogen co-doped carbon (M-Nx /C) materials with tailored morphology, tunable composition, and confined structure show great potential in both acidic and alkaline media. Herein, the mechanism of ORR is provided, followed by recent efforts to clarify the actual structures of active sites. Furthermore, the progress of optimizing the catalytic performance of M-Nx /C catalysts by modulating nitrogen-rich precursors and porous structure engineering is highlighted. The remaining challenges and development prospects of M-Nx /C catalysts are also outlined and evaluated.

Inhibition of endothelial nitric oxide synthase reverses the effect of exercise on improving cognitive function in hypertensive rats.

Hypertension-induced endothelial dysfunction is associated with ß-amyloid (Aß) deposition, a typical pathology of Alzheimer's disease (AD). Endothelial nitric oxide synthase (eNOS) phosphorylation, impaired by phosphatidylinositol 3-kinase (PI3K)/protein kinase-B(Akt) pathway abnormalities in hypertensive rats, has a critical role in endothelial function. However, it is unknown whether eNOS participates in the hypertension-induced pathology of AD. In this study, we investigated the role of eNOS in Aß deposition and cognitive function in stroke-prone spontaneously hypertensive (SHRSP) rats. Physical exercise was used as a promoter, and Nω-nitro L-arginine methyl ester (L-NAME) was used as an inhibitor of eNOS to determine the effects of eNOS on SHRSP rats. Compared with Wistar Kyoto (WKY) rats, the hypertensive challenge caused cognitive impairment, decreased eNOS levels and increased amyloid precursor protein (APP), ß-secretase, and Aß levels in the cortex and hippocampus. Sixteen weeks of exercise lowered blood pressure (BP), promoted eNOS expression, ameliorated Alzheimer's pathology, and improved cognitive function in 29-week-old SHRSP rats. Furthermore, daily treatment with L-NAME reversed the beneficial effects of exercise on SHRSP rats. Exercise also decreased the protein levels of insulin-like growth factor-1 (IGF-1), PI3K, and phospho-Akt (p-Akt, ser473). In addition, long-term exercise increased the expression levels of IGF-1, PI3K, and p-Akt (ser473) in the brains of SHRSP rats. In conclusion, eNOS downregulation contributed to hypertension-induced Alzheimer pathology and cognitive impairment. Long-term exercise initiated in rats at a young age promoted eNOS expression and attenuated vascular-related Alzheimer's pathology via the IGF-1/PI3K/p-Akt pathway in SHRSP rats.

Physical Exercise Promotes Novel Object Recognition Memory in Spontaneously Hypertensive Rats after Ischemic Stroke by Promoting Neural Plasticity in the Entorhinal Cortex.

Cerebral ischemia leads to memory impairment, and several studies have indicated that physical exercise (PE) has memory-improving effects after ischemia. This study was designed to further explore the specific role of PE in novel object recognition (NOR) memory after stroke and the exact cortical regions in which memory is restored by PE. Spontaneously hypertensive rats (SHR) were subjected to transient middle cerebral artery occlusion (tMCAO) or sham surgery, followed by 26 days of PE starting on day 3 post-tMCAO. Thereafter, infarct volume, neurobehavioral outcome and NOR memory were assessed. Immunofluorescence staining and Luxol Fast Blue (LFB) staining were performed in the prefrontal cortex, entorhinal cortex and corpus callosum regions. Western blot analysis was performed to detect expressions of Nestin, Bcl-2 and SYN proteins in the entorhinal cortex. After tMCAO, NOR memory impairment was found in SHR. Rats subjected to PE post-tMCAO showed increased discrimination ratio, as well as significant decreases in infarct volumes and modified neurological severity scores (mNSS), when compared with tMCAO rats without PE. After stroke, NeuN-positive cell number was drastically reduced in the entorhinal cortex, rather than in the prefrontal cortex. Ischemic stroke had no impact on myelin and phospholipids, and the ratio of SMI-32/MBP in the corpus callosum. PE increased NeuN, Nestin, Ki67, MBP, SYN, PSD-95 and Bcl-2 expressions in the entorhinal cortex, while TUNEL and SMI-32 expressions were decreased. In conclusion, the NOR memory-improving capacity promoted by PE was closely related to neuronal cell proliferation and synaptic plasticity of the entorhinal cortex.

Physical Exercise Improves Cognitive Function Together with Microglia Phenotype Modulation and Remyelination in Chronic Cerebral Hypoperfusion.

Myelin is closely associated with cognitive function and is extremely vulnerable to damage in ischemic cerebrovascular diseases. The failure of remyelination is mainly due to limitations in oligodendrocyte progenitor cells (OPCs) differentiation in the damaged area. Previous studies have shown that physical exercise can improve vascular cognitive impairment, but whether it can reverse the defect in remyelination during ischemic injury and the underlying mechanism remains unclear. In this study, we observed the effects of physical exercise on chronic cerebral hypoperfusion (CCH) established by bilateral carotid artery occlusion. The cognitive function, myelin integrity, OPCs proliferation and differentiation, as well as microglia polarization were analyzed at 28 days after CCH. Besides, the expression of CX3CL1/CX3CR1 axis and activation of mitogen-activated protein kinase (MAPK) signal cascades were also evaluated. We found that physical exercise improved the cognitive function of rats with CCH, alleviated myelin injury, triggered OPCs proliferation and differentiation, facilitated microglia polarization toward M2, augmented the expression of CX3CL1/CX3CR1 axis, and reduced ERK and JNK phosphorylation. The results indicated that physical exercise improved the cognitive function of rats with CCH, possibly through microglial phenotype modulation and enhancement of oligodendrocytegenesis and remyelination. Moreover, the CX3CL1/CX3CR1 axis played an important role in this process by mediating ERK- and JNK-dependent pathways.

Inhibition of c-Myc overcomes cytotoxic drug resistance in acute myeloid leukemia cells by promoting differentiation.

Nowadays, drug resistance still represents a major obstacle to successful acute myeloid leukemia (AML) treatment and the underlying mechanism is not fully elucidated. Here, we found that high expression of c-Myc was one of the cytogenetic characteristics in the drug-resistant leukemic cells. c-Myc over-expression in leukemic cells induced resistance to chemotherapeutic drugs, enhanced colony formation capacity and inhibited cell differentiation induced by all-trans retinoic acid (ATRA). Meanwhile, inhibition of c-Myc by shRNA or specific c-Myc inhibitor 10058-F4 rescued the sensitivity to cytotoxic drugs, restrained the colony formation ability and promoted differentiation. RT-PCR and western blotting analysis showed that down-regulation of C/EBPß contributed to the poor differentiation state of leukemic cells induced by c-Myc over-expression. Importantly, over-expression of C/EBPß could reverse c-Myc induced drug resistance. In primary AML cells, the c-Myc expression was negatively correlated with C/EBPß. 10058-F4, displayed anti-proliferative activity and increased cellular differentiation with up-regulation of C/EBPß in primary AML cells. Thus, our study indicated that c-Myc could be a novel target to overcome drug resistance, providing a new approach in AML therapy.