Mixed Receptive Fields Augmented YOLO with Multi-Path Spatial Pyramid Pooling for Steel Surface Defect Detection.

Aiming at the problems of low detection efficiency and poor detection accuracy caused by texture feature interference and dramatic changes in the scale of defect on steel surfaces, an improved YOLOv5s model is proposed. In this study, we propose a novel re-parameterized large kernel C3 module, which enables the model to obtain a larger effective receptive field and improve the ability of feature extraction under complex texture interference. Moreover, we construct a feature fusion structure with a multi-path spatial pyramid pooling module to adapt to the scale variation of steel surface defects. Finally, we propose a training strategy that applies different kernel sizes for feature maps of different scales so that the receptive field of the model can adapt to the scale changes of the feature maps to the greatest extent. The experiment on the NEU-DET dataset shows that our model improved the detection accuracy of crazing and rolled in-scale, which contain a large number of weak texture features and are densely distributed by 14.4% and 11.1%, respectively. Additionally, the detection accuracy of inclusion and scratched defects with prominent scale changes and significant shape features was improved by 10.5% and 6.6%, respectively. Meanwhile, the mean average precision value reaches 76.8%, compared with the YOLOv5s and YOLOv8s, which increased by 8.6% and 3.7%, respectively.

Impact of neural stem cell-derived extracellular vesicles on mitochondrial dysfunction, sirtuin 1 level, and synaptic deficits in Alzheimer's disease.

Small extracellular vesicles (EVs), including exosomes, play multiple physiological roles. In neurodegenerative diseases, EVs can be pivotal in dispersing neuropathogenic proteins. This study investigates the role of neural stem cell (NSC)-derived EVs in a transgenic (Tg) mouse model of Alzheimer's disease (AD). Five weeks following treatment on 9-month-old APP/PS1 mice, the effects of NSC-derived EVs on cognitive behavior, mitochondrial function, sirtuin1 (SIRT1), synaptic function and morphology, quantification of amyloid-ß (Aß) level, and inflammatory response were investigated. The results showed that mice in the Tg-NSCs-ev group exhibited significant improvement in cognitive performance compared with Tg-Veh group. Furthermore, the expression of mitochondrial function-related factors (peroxisome proliferator-activated receptor-γ coactivator-1α [PGC1α], nuclear respiratory factor 1 and 2 [NRF1 and 2], and fission 1 [Fis1]), SIRT1 as well as synaptic proteins (growth-associated protein 43 [GAP43], synaptophysin [SYP], post-synaptic density 95 [PSD95] and microtubule-associated protein 2 [MAP2]) were significantly higher in the Tg-NSCs-ev group, when compared with the Tg-Veh group. In addition, oxidative damage markers (anti-4-Hydroxynonenal [4-HNE] and anti-3 nitrotyrosine [3-NT]), inflammatory cytokines and the microglial marker (Iba1) were significantly lower in the Tg-NSCs-ev group, compared to the Tg-Veh group. Moreover, synaptic morphology was distinctly improved in the Tg-NSCs-ev group, whereas the Aß level was not altered. Our study provides novel evidences that NSC-derived EVs enhanced mitochondrial function, SIRT1 activation, synaptic activity, decreased inflammatory response, and rescued cognitive deficits in AD like mice.

NSCs promote hippocampal neurogenesis, metabolic changes and synaptogenesis in APP/PS1 transgenic mice.

Adult neurogenesis and synaptic remodeling persist as a unique form of structural and functional plasticity in the hippocampal dentate gyrus (DG) and subventricular zone (SVZ) of the lateral ventricles due to the existence of neural stem cells (NSCs). Transplantation of NSCs may represent a promising approach for the recovery of neural circuits. Here, we aimed to examine effects of highly neuronal differentiation of NSCs transplantation on hippocampal neurogenesis, metabolic changes and synaptic formation in APP/PS1 mice. 12-month-old APP/PS1 mice were used for behavioral tests, immunohistochemistry, western blot, transmission electron microscopy and proton magnetic resonance spectroscopy (1H-MRS). The results showed that N-acetylaspartate (NAA) and Glutamate (Glu) levels were increased in the Tg-NSC mice compared with the Tg-PBS and Tg-AD mice 10 weeks after NSCs transplantation. NSC-induced an increase in expression of synaptophysin and postsynaptic protein-95, and the number of neurons with normal synapses was significantly increased in Tg-NSC mice. More doublecortin-, BrdU/NeuN- and Nestin-positive neurons were observed in the hippocampal DG and SVZ of the Tg-NSC mice. This is the first demonstration that engrafted NSCs with a high differentiation rate to neurons can enhance neurogenesis in a mouse model of AD and can be detected by 1H-MRS in vivo. It is suggested that engraft of NSCs can restore memory and promote endogenous neurogenesis and synaptic remodeling, moreover, 1H-MRS can detect metabolite changes in AD mice in vivo. The observed changes in NAA/creatine (Cr) and glutamate (Glu)/Cr may be correlated with newborn neurons and new synapse formation.

The value of whole-brain CT perfusion imaging and CT angiography using a 320-slice CT scanner in the diagnosis of MCI and AD patients.

OBJECTIVES: To validate the value of whole-brain computed tomography perfusion (CTP) and CT angiography (CTA) in the diagnosis of mild cognitive impairment (MCI) and Alzheimer's disease (AD). METHODS: Whole-brain CTP and four-dimensional CT angiography (4D-CTA) images were acquired in 30 MCI, 35 mild AD patients, 35 moderate AD patients, 30 severe AD patients and 50 normal controls (NC). Cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), time to peak (TTP), and correlation between CTP and 4D-CTA were analysed. RESULTS: Elevated CBF in the left frontal and temporal cortex was found in MCI compared with the NC group. However, TTP was increased in the left hippocampus in mild AD patients compared with NC. In moderate and severe AD patients, hypoperfusion was found in multiple brain areas compared with NC. Finally, we found that the extent of arterial stenosis was negatively correlated with CBF in partial cerebral cortex and hippocampus, and positively correlated with TTP in these areas of AD and MCI patients. CONCLUSIONS: Our findings suggest that whole-brain CTP and 4D-CTA could serve as a diagnostic modality in distinguishing MCI and AD, and predicting conversion from MCI based on TTP of left hippocampus. KEY POINTS: • Whole-brain perfusion using the full 160-mm width of 320 detector rows • Provide clinical experience of 320-row CT in cerebrovascular disorders of Alzheimer's disease • Initial combined 4D CTA-CTP data analysed perfusion and correlated with CT angiography • Whole-brain CTP and 4D-CTA have high value for monitoring MCI to AD progression • TTP in the left hippocampus may predict the transition from MCI to AD.

Neural stem cell transplantation decreases neuroinflammation in a transgenic mouse model of Alzheimer's disease.

Inflammatory processes are considered to play an important role in the progression of neurodegenerative changes in Alzheimer's disease (AD). A number of studies have reported that inflammatory processes are highly correlated with cognitive deficits in AD-like mice. Transplantation of neural stem cells (NSCs) has been considered as a potential new therapy for the treatment of AD because of its effects in improving cognitive ability. However, NSCs have not been evaluated for their protective effects against inflammatory changes in AD. Here, we injected NSCs into amyloid precursor protein (APP)/PS1 transgenic mice to analyse cognitive function and to measure glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor molecule-1 (Iba-1) and toll-like receptors 4(TLR4) activation. We also quantified TLR-4 pathway-related agents, Aß concentration and the levels of proinflammatory mediators. Our results showed that in NSC-injected APP/PS1 mice, activation of GFAP, Iba-1, TLR4 and TLR4 pathway-related agents (MyD88, TRIF, P38 MAPK and NF-κB P65) were significantly decreased with decreased expression of proinflammatory mediators (IL-1, IL-6, TNF-α and PGE2). These changes were associated with the amelioration of cognitive deficits, but no difference was found in Aß concentration. Our results provide novel evidence that NSC transplantation in APP/PS1 mice significantly improved cognitive deficits and was accompanied by the attenuation of inflammatory injury via suppression of glial and TLR4-mediated inflammatory pathway activation. Our data indicate that these pathways may potentially be important therapeutic targets to prevent or delay AD. This study investigated the neuroprotective effect of neural stem cell (NSC) transplantation against Alzheimer's disease (AD) inflammation. We found that NSC treatment in APP/PS1 mice significantly improved cognitive deficits and was accompanied by the attenuation of inflammatory injury via suppression of glial and toll-like receptor 4 (TLR4) activation and its downstream signalling pathways. Our findings indicate that these pathways may be potentially important therapeutic targets to prevent or delay AD.

[Effects of transplanted neural stem cells on synaptogenesis in APP/PS1 mice].

OBJECTIVE: To explore the effects of transplanted neural stem cells (NSCs) on synaptogenesis in an Alzheimer' disease (AD) murine model and related mechanism. METHODS: Twenty 9-month-old APP/PS1 double transgenic mice were randomly divided into 2 groups. One group received NSCs transplantation (NSC group) in bilateral hippocampi while another group received an equal volume of 0.01 mol/L phosphate buffer saline (PBS group) as a negative control group. Ten wild-type mice were selected as the positive control group (WT group) without any treatment. After 8-week transplantation, the expressions of synaptophysin (SYN) and growth associated protein-43 (GAP-43) proteins in hippocampal areas were analyzed by immunofluorescence and Western blot. The number and structure of synapses in transplanted regions were observed by electron microscopy. RESULTS: (1) Immunofluorescence staining showed that NSC-induced neurons highly expressed SYN and GAP-43 at the protein levels; (2) the expression of SYN and GAP-43 significantly increased in the NSC group versus the PBS group (F = 58.367, P < 0.01; F = 75.296, P < 0.01). No difference existed in the SYN level between NSC and WT groups (P > 0.05). However, the GAP-43 expression was significantly higher than that of the WT group (P < 0.01); (3) ultrastructure showed that the number of synapses in the NSC group with normal morphology (12.1 ± 2.1) increased than that in the PBS group (6.5 ± 2.2) (F = 15.981, P < 0.01). No difference existed between NSC and WT groups (11.0 ± 1.4) (P > 0.05). CONCLUSION: NSC-induced neurons increase the number of synapses by an up-regulation of synaptic proteins, SYN and GAP-43. Thus synaptogenesis may be a key factor in improving the symptom of AD mice.

[Effects of neural stem cells transplanted into an animal model of Alzheimer disease on Aß plaques].

OBJECTIVE: To explore the effects on Aß plaques of neural stem cells transplanted into an Alzheimer disease mouse model. METHODS: A total of twenty 12-months-old APP+PS1 double transgenic AD mice were randomly divided into two groups.One group received neural stem cells transplantation, that was NSC group, another mice received an equal quantity 0.01 mol/L PBS, as positive control group. After 5 weeks transplantation, the total number of Aß plaques examined by immunohistochemistry, the ratio of compact of Aß plaques by TS staining, and whether NSCs migrate into Aß plaques by immunofluorescence monitoring. RESULTS: There was no difference in total number of Aß plaques between NSC group (181 ± 12) and PBS (179 ± 14) group after transplantation (P > 0.05). There was no difference in the number of TS+ plaques between NSC group (54.9%) and PBS (55.7%) group after eight weeks NSCs transplantation (P > 0.05). (2) However, engrafted NSCs showed partial chemotaxis toward Aß plaques. CONCLUSION: NSCs transplantation did not have a significant impact on Aß plaques of AD mice, but the tropism of engrafted NSCs may be capable of replacing lost or damaged cells and reverse the course of AD mice in some extent.

Normoxic induction of cerebral HIF-1alpha by acetazolamide in rats: role of acidosis.

Acetazolamide has been recognized as an effective treatment for acute mountain sickness. The efficacy of acetazolamide is related to metabolic acidosis, which promotes chemoreceptors to respond to hypoxic stimuli at altitude. In this study, adult male Sprague-Dawley rats were treated with acetazolamide (100mg/kg or 50mg/kg, I.P.) for 3 days. Primary cultured cortical neurons and PC12 cell lines were exposed to acidosis-permissive (pH 6.5) or standard (pH 7.2) media for 20h. HIF-1alpha and its target genes were assayed by Western blot, real-time PCR, HIF-1 DNA-binding assay and chloramphenicol acetyltransferase reporter gene assay. HIF-1alpha protein level and HIF-1 DNA-binding activities were increased in cerebral cortices of rats treated with acetazolamide. Moreover, the mRNA levels of erythropoietin, vascular endothelial growth factor, and glucose transporter-1 also increased. The HIF-1alpha protein level and activity of HIF-driven chloramphenicol acetyltransferase reporters of cortical neurons and PC12 cells treated with acidosis media were significantly enhanced. We conclude that the normoxic induction of HIF-1alpha and HIF-1 mediated genes by acetazolamide may mediate the effect of acetazolamide in the reduction of symptoms of acute mountain sickness.

Mechanism of ischemic tolerance induced by hyperbaric oxygen preconditioning involves upregulation of hypoxia-inducible factor-1alpha and erythropoietin in rats.

We studied the effect of hyperbaric oxygen (HBO) preconditioning on the molecular mechanisms of neuroprotection in a rat focal cerebral ischemic model. Seventy-two male Sprague-Dawley rats were pretreated with HBO (100% O(2), 2 atmospheres absolute, 1 h once every other day for 5 sessions) or with room air. In experiment 1, HBO-preconditioned rats and matched room air controls were subjected to focal cerebral ischemia or sham surgery. Postinjury motor parameters and infarction volumes of HBO-preconditioned rats were compared with those of controls. In experiment 2, HBO-preconditioned rats and matched room air controls were killed at different time points. Brain levels of hypoxia-inducible factor-1alpha (HIF-1alpha) and its downstream target gene erythropoietin (EPO) analyzed by Western blotting and RT-PCR as well as HIF-1alpha DNA-binding and transcriptional activities were determined in the ipsilateral hemisphere. HBO induced a marked increase in the protein expressions of HIF-1alpha and EPO and the activity of HIF-1alpha, as well as the expression of EPO mRNA. HBO preconditioning dramatically improved the neurobehavioral outcome at all time points (3.0 +/- 2.1 vs. 5.6 +/- 1.5 at 4 h, 5.0 +/- 1.8 vs. 8.8 +/- 1.4 at 8 h, 6.4 +/- 1.8 vs. 9.7 +/- 1.3 at 24 h; P < 0.01, respectively) and reduced infarction volumes (20.7 +/- 4.5 vs. 12.5 +/- 3.6%, 2,3,5-Triphenyltetrazolium chloride staining) after cerebral ischemia. This observation indicates that the neuroprotection induced by HBO preconditioning may be mediated by an upregulation of HIF-1alpha and its target gene EPO.

Hyperbaric oxygen preconditioning promotes angiogenesis in rat liver after partial hepatectomy.

Hyperbaric oxygen preconditioning (HBO-PC) increases the level of HIF-1alpha (hypoxia inducible factor-1alpha) and its target gene VEGF (vascular endothelial growth factor) which is involved in angiogenesis. Liver regeneration is an angiogenesis-dependent process. We hypothesized that HIF-1alpha and VEGF mediated the angiogenesis effect of HBO-PC on regenerating rat liver. Male Sprague Dawley rats received HBO-PC followed by 70% partial hepatectomy. Proliferation of hepatocytes and endothelial cells was evaluated by BrdU (bromodeoxyuridine) staining. Microvascular density was assessed by immunohistochemistry. mRNA expression of HIF-1alpha was assessed by quantitative RT-PCR and protein levels of HIF-1alpha and VEGF were assessed by western blot. HIF-1alpha DNA-binding activity was determined with an ELISA-based kit. HBO-PC increased the proliferation index of endothelial cells and microvascular density at 48 h after partial hepatectomy. The protein level and DNA-binding activity of HIF-1alpha and the protein level of VEGF were increased by HBO-PC before and after partial hepatectomy. Partial hepatectomy alone also increased proliferation index and the expressions of HIF-1alpha and VEGF. Our results indicated that the angiogenesis effect of HBO-PC on liver after partial hepatectomy could be achieved by increased HIF-1alpha activity and VEGF expression. However, the angiogenic effect of HBO-PC is moderate and HBO-PC failed to produce additional effect on the enhancement of HIF-1alpha and VEGF induced by partial hepatectomy alone.

GDF11 Rejuvenates Cerebrovascular Structure and Function in an Animal Model of Alzheimer's Disease.

Cerebral amyloid angiopathy (CAA) is present in up to 90% of patients with Alzheimer's disease (AD), and may interact with classical neuropathology to exacerbate cognitive decline. Since growth differentiation factor 11 (GDF11) can activate vascular remodeling, we tested its effects on cognitive function and neuroinflammatory changes of AD model mice. We intravenously administered GDF11 or vehicle daily to 12-month-old transgenic mice overexpressing the amyloid-ß protein precursor (AßPP)/PS1). Cognitive function was monitored using the Morris water maze, and after conclusion of the treatment, we assessed the morphology and presence of inflammatory markers in the cerebral vasculature. Subchronic treatment of adult AßPP/PS1 mice with GDF11 rescued cognitive function and ameliorated cerebrovascular function. In particular, the de novo genesis of small blood vessels and the expression of vascular-related proteins were significantly higher than in the vehicle-treated AßPP/PS1 mice, whereas the expressions of the inflammatory markers Iba-1 and GFAP significantly decreased in proportion to the lower ratio of two forms of amyloid-ß (Aß40/42). Daily intravenous treatment with GDF11-injection can rejuvenate respects of cognition and cerebrovascular changes in AD mice.

Therapeutic effects of hyperbaric oxygen in a rat model of endothelin-1-induced focal cerebral ischemia.

It has been established that hyperbaric oxygen (HBO) treatment reduces brain edema, decreases infarct volume, contributes to neurological functional recovery and suppresses apoptosis in suture-induced focal cerebral ischemic animal models. In the present study, we evaluated the therapeutic effect of HBO in an endothelin-1-induced focal cerebral ischemia in rats and explored the associated mechanisms of HBO-induced brain protection. One hundred twenty male Sprague-Dawley rats (280 to 320 g) were randomly assigned to sham, focal cerebral ischemia and focal cerebral ischemia treated with HBO groups. Brain water content, neurological function, morphology and molecular biological markers were assessed. HBO (100% O2, 2.5 atmosphere absolute for 2 h) was initiated at 1 h after focal cerebral ischemia. Rats were killed at 24 h to harvest tissues for Western blot or for histology. In HBO-treated animals, an enhanced ratio of Bcl-2 and Bax and a reduced expression of hypoxia-inducible factor-1alpha (HIF-1alpha) in the hippocampus after focal cerebral ischemia were observed. These results indicate that HBO provides brain protection that is probably associated with the inhibition of HIF-1alpha and the elevation of Bcl-2.

Polyethylene glycol-poly(ε-benzyloxycarbonyl-l-lysine)-conjugated VEGF siRNA for antiangiogenic gene therapy in hepatocellular carcinoma.

A polyethylene glycol-poly(ε-benzyloxycarbonyl-l-lysine) (PEG-SS-PLL) block copolymer based on a disulfide-linked, novel biodegradable catiomer bearing a PEG-sheddable shell was developed to avoid "PEG dilemma" in nanoparticle intracellular tracking of PEG-PLL where PEG was nondegradable. However, PEG-SS-PLL catiomers have not been used to deliver small interfering VEGF RNA (siVEGF) in antiangiogenesis gene therapy. In this study, we aimed to investigate whether this novel biodegradable catiomer can deliver siVEGF into cancer cells and at the same time have an antitumor effect in a xenograft mouse model. It was found that PEG-SS-PLL efficiently delivered siVEGF with negligible cytotoxicity, and significantly decreased the expression of VEGF at both the messenger-RNA and protein levels both in vitro and in vivo, and thus tumor growth was inhibited. Our findings demonstrated that PEG-SS-PLL/siVEGF could potentially be applied to antiangiogenesis gene therapy for hepatocellular carcinoma.

[Application of modified adjustable skin stretching and secure wound-closure system in repairing of skin and soft tissue defect].

Objective: To investigate the application of modified adjustable skin stretching and secure wound-closure system in repairing of skin and soft tissue defect. Methods: Between March 2016 and April 2017, 21 cases of skin and soft tissue defects were repaired with the modified adjustable skin stretching and secure wound-closure system (the size of regulating pressure and the times of adjustment were determined according to the color, temperature, capillary response, and swelling degree of the skin edge). There were 11 males and 10 females, with an average age of 49.2 years (range, 21-67 years). Among them, 1 case was the residual wound after amputation of leg; 18 cases were the wounds after traumatic injury operation, including 4 cases in the lower leg, 3 cases in the knee joint, 7 cases in the upper limb, and 4 cases in the foot; and 2 cases were diabetic feet. The skin defect area ranged from 4.0 cm×2.5 cm to 21.0 cm×10.0 cm. Results: Skin defect wounds closed directly in one stage in 4 cases; 12 cases were closed after continuously stretching for 5-14 days (mean, 10 days); 5 cases were reduced to less than one-half area, and the wound healed after the second skin grafting or flap repairing. All the 21 patients were followed up 3-12 months (mean, 5.2 months). The wound was linear healing with small scar, and no invasive margin, poor blood flow, necrosis, and poor sensory function happened. Conclusion: The modified adjustable skin stretching and secure wound-closure system can reduce the skin and soft tissue defects or close the wound directly, and even replace the skin graft and skin flap repairing. It was a good method for the treatment of skin and soft tissue defect.

[Changes in the activities of enzymes involved in starch synthesis and accumulation in caryopsis of transgenic rice with antisense Wx gene].

The amylose content of rice caryopsis is determined by Wx protein, one kind of granule-bound starch synthetase which is encoded by Wx gene. Different rice types and species have different levels of Wx gene expression and have different amylose contents in their caryopsis. Wuyunjing No.7 (2200), the japonica rice with an amylose content 17% and its transgenic rice lines with antisense Wx gene (2201 and 2203, with amylose contents 8.5% and 2% respectively), and Longtefu (LP03), the indica rice with a high amylose content (28%) and its transgenic rice with antisense Wx gene (A199, with an amylose content 9%) were used to investigate the effects of Wx protein content decrease on the activities of enzymes involved in starch synthesis and thereby starch accumulation. The results indicated that with the decrease in Wx protein, the amylose content in transgenic caryopsis was reduced accordingly, whereas the amylopectin content per caryopsis (mg/grain) was not affected, and made the total starch content in transgenic caryopsis markedly lower than their parents. With the development of caryopsis, the amylose/total starch ratio was not changed significantly in the two parent caryopses, LP03 and 2200, but it went down gradually in their transgenic caryopses. The amylose/total starch ratio in transgenic caryopses was very significantly lower than their parents in the same period. The activities of ADP-glucose pyrophosphorylase (ADPG-PPase), granule-bound starch synthase (GBSS), soluble starch synthase (SSS) and starch branching enzyme (SBE) rose rapidly in early periods of grain filling, and soon reached their maximum, then reduced quickly until the middle and later periods of grain filling. Compared with the parents, the GBSS activity in transgenic caryopsis was significantly lowered, and correlated with the amylose reduction. Besides, the maximum activity of GBSS appeared earlier, and the range of the activity was smaller. In transgenic caryopsis, the activities of ADPG-PPase and SSS were higher than their parents in early and middle periods of grain filling, while the SBE activity was higher than their parents in middle and late periods.

Ultrasound-induced microbubble destruction promotes targeted delivery of adipose-derived stem cells to improve hind-limb ischemia of diabetic mice.

This study aimed to investigate whether ultrasound-induced microbubble destruction was able to promote targeted delivery of adipose-derived stem cells (ASCs) to improve hind-limb ischemia of diabetic mice. Ischemia was induced in the lower limb of db/db mice which were then randomly divided into 5 groups: PBS group, Sham group, ultrasound + microbubble group (US+MB), US+MB+ASCs group and ASCs group. Contrast-enhanced ultrasound perfusion imaging showed the ratio of blood flow in ischemic hind-limb to that in contralateral limb increased over time in five groups. A significant enhancement in US+MB+ASCs group was observed compared with US+MB group (P<0.01). Immunofluorescence microscopy of hind-limb muscle showed the microvessel density (microvessels/skeletal muscle fibers) and arteriolar density in US+MB+ASCs group were higher than in US+MB group, and significantly higher than in other control groups (P<0.01). Masson staining indicated the degree of muscle fibrosis in US+MB+ASCs group was lower than in US+MB. 3 and 7 days after therapy, ELISA and RT-PCR showed the expression of VEGF, P-selectin, ICAM-1 and SDF-1 in US+MB+ASCs group was higher than in US+MB group, and dramatically increased as compared to other groups (P<0.01). 3 and 7 days after therapy, Western blot assay showed the protein expression of P-P13K, P-AKT, VEGF, P-selectin, ICAM-1 and SDF-1 in US+MB+ASCs group was higher than US+MB group (P<0.01). The bioeffects of ultrasound-induced microbubble cavitation is able to up-regulate the expression of pro-inflammatory cytokines, which may improve the targeted delivery, adhesion and paracrine of ASCs, attenuating the hind-limb ischemia in diabetic mice.

Effects of Sevoflurane on Young Male Adult C57BL/6 Mice Spatial Cognition.

Inhalation anesthetics are reported to affect cognition in both animals and humans. The influence of inhalation anesthetics in learning and memory are contradictory. We therefore investigated the effects of sevoflurane anesthesia with different durations on cognitive performance and the levels of NMDA receptor subunit NR2B, phosphorylated ERK1/2 (p-ERK1/2) and activated caspase3 in mouse hippocampus. We anaesthetized eight-week old male C57BL/6 mice with 2.5% sevoflurane for durations ranging from one to four hours. Non-anaesthetized mice served as controls. Mice exposed to sevoflurane for one to three hours showed improved performance, whereas mice with exposure up to four hours displayed similar behavioral performance as control group. NR2B was increased both at 24h and at two weeks post sevoflurane exposure in all groups. The p-ERK1/2: total ERK1/2 ratio increased at 24h in all anesthesia groups. The ratio remained elevated at two weeks in groups with two- to four-hour exposure. Activated caspase3 was detected elevated at 24h in groups with two- to four-hour exposure. The elevated trend of activated caspase3 was still detectable at two weeks in groups with three- to four-hour exposure. At two weeks post anesthesia, the typical morphology associated with apoptotic cells was observed in the hippocampus of mice exposed to four hours of sevoflurane. Our results indicate that 2.5% sevoflurane exposure for one to three hours improved spatial cognitive performance in young adult mice. The cognitive improvement might be related to the increase of NR2B, the p-ERK1/2: total ERK1/2 ratio in hippocampus. However, exposure to sevoflurane for four hours caused neurotoxicity due to caspase3 activation and apoptosis.

Neural stem cell transplantation enhances mitochondrial biogenesis in a transgenic mouse model of Alzheimer's disease-like pathology.

Mitochondrial dysfunction, especially a defect in mitochondrial biogenesis, is an early and prominent feature of Alzheimer's disease (AD). Previous studies demonstrated that the number of mitochondria is significantly reduced in susceptible hippocampal neurons from AD patients. Neural stem cell (NSC) transplantation in AD-like mice can compensate for the neuronal loss resulting from amyloid-beta protein deposition. The effects of NSC transplantation on mitochondrial biogenesis and cognitive function in AD-like mice, however, are poorly understood. In this study, we injected NSCs or vehicle into 12-month-old amyloid precursor protein (APP)/PS1 transgenic mice, a mouse model of AD-like pathology. The effects of NSC transplantation on cognitive function, the amount of mitochondrial DNA, the expression of mitochondrial biogenesis factors and mitochondria-related proteins, and mitochondrial morphology were investigated. Our results show that in NSC-injected APP/PS1 (Tg-NSC) mice, the cognitive function, number of mitochondria, and expression of mitochondria-related proteins, specifically the mitochondrial fission factors (dynamin-related protein 1 [Drp1] and fission 1 [Fis1]) and the mitochondrial fusion factor optic atrophy 1 (OPA1), were significantly increased compared with those in age-matched vehicle-injected APP/PS1 (Tg-Veh) mice, whereas the expression of mitochondrial fusion factors mitofusion 1 (Mfn1) and Mfn2 was significantly decreased. These data indicate that NSC transplantation may enhance mitochondria biogenesis and further rescue cognitive deficits in AD-like mice.

Effects of different concentration and duration time of isoflurane on acute and long-term neurocognitive function of young adult C57BL/6 mouse.

Postoperative cognitive dysfunction (POCD) is a decline in cognitive performance after a surgery with anaesthesia. The exact reasons of surgery and/or anaesthesia resulting in POCD are unclear. The aim of this study is to investigate the effects of different concentration and duration time of isoflurane anaesthesia on cognitive performance and cellular mechanisms involved in learning and memory function. In present work, young adult male C57BL/6 mice (age: 8 weeks) were anaesthetized by different concentration isoflurane in 100% oxygen for different duration time (Mice in group I1 received 0.7% isoflurane 0.5 h, mice in I2 received 0.7% isoflurane 2 h, mice in I3 received 1.4% isoflurane 2 h, and mice in I4 received 1.4% isoflurane 4 h). Non-anaesthetized mice served as control group (I0). Spatial learning was assessed at 10 days post-anesthesia in Morris water maze (MWM). Hippocampal protein expressions of activated caspase 3, NMDA receptor subunit NR2B, and extracellular-signal regulated kinase (ERK) 1/2 were evaluated 24 hours and 2 weeks post anesthesia. Protein expression of activated caspase3 was detected acute elevated in I3 (24 h post-anesthesia) and acute and long-term elevated in I4 (24 hours and 2 weeks post-anesthesia). There was no significant difference between I1, I2 and control group. Protein expressions of NR2B showed an acute and long-term increasement in I1 and I2, decreasement in I4, and an acute decline, then returned to normal in I3 compared to control group. The ratio of phosopho-ERK1/2 to total-ERK showed an acute increasement in I1 and I2, then came to normal 2 weeks post anesthesia compared to control group, meanwhile, we detected an acute and long-term decline in I3 and I4. In MWM test, mice in I1 and I2 showed cognitive improvement, mice in I3 showed similar to control group, while mice in I4 demonstrated cognitive impairment, which were approximately corresponding to the changes of protein expression of NR2B and activation of ERK1/2. The present data suggested the following: (1) Isoflurane may cause neurotoxicity by inducing caspase activation and apoptosis with the anesthetic concentration increased and duration prolonged. (2) Low concentration of isoflurane in 2 hours can induce a hippocampus-specific elevation of NR2B subunit composition and ratio of p-ERK1/2 to total ERK1/2, produce hippocampal-dependent cognitive improvement. While high concentration of isoflurane exceeding 4 hours may induce a decline of NR2B and ratio of pERK1/2 to ERK1/2, then result in cognitive impairment.