Variable Stiffness Conductive Composites by 4D Printing Dual Materials Alternately

Materials that can be designed with programmable properties and which change in response to external stimuli are of great importance in numerous fields of soft actuators, involving robotics, drug delivery and aerospace applications. In order to improve the interaction of human and robots, materials with variable stiffness are introduced to develop their compliance. A variable stiffness composite has been investigated in this paper, which is composed of liquid metals (LMs) and silicone elastomers. The phase changing materials (LMs) have been encapsulated into silicone elastomer by printing the dual materials alternately with three-dimensional direct ink writing. Such composites enable the control over their own stiffness between soft and rigid states through LM effective phase transition. The tested splines demonstrated that the stiffness changes approximately exceeded 1900%, and the storage modulus is 4.75 MPa and 0.2 MPa when LM is rigid and soft, respectively. In the process of heating up, the stretching strain can be enlarged by at least three times, but the load capacity is weakened. At a high temperature, the resistance of the conductive composites changes with the deformation degree, which is expected to be applied in the field of soft sensing actuators

New insights into the roles of oligodendrocytes regulation in ischemic stroke recovery

Oligodendrocytes (OLs), the myelin-forming cells of the central nervous system, are integral to axonal integrity and function. Hypoxia-ischemia episodes can cause severe damage to these vulnerable cells through excitotoxicity, oxidative stress, inflammation, and mitochondrial dysfunction, leading to axonal dystrophy, neuronal dysfunction, and neurological impairments. OLs damage can result in demyelination and myelination disorders, severely impacting axonal function, structure, metabolism, and survival. Adult-onset stroke, periventricular leukomalacia, and post-stroke cognitive impairment primarily target OLs, making them a critical therapeutic target. Therapeutic strategies targeting OLs, myelin, and their receptors should be given more emphasis to attenuate ischemia injury and establish functional recovery after stroke. This review summarizes recent advances on the function of OLs in ischemic injury, as well as the present and emerging principles that serve as the foundation for protective strategies against OLs deaths

Neural transmission pathways are involved in the neuroprotection induced by post- but not perischemic limb remote conditioning

Background: Remote ischemic preconditioning (PreC) and postconditioning (PostC) have all been shown to be neuroprotective against ischemia/reperfusion (I/R) injury. However, the underlying mechanisms of ischemic perconditioning (PerC) remain largely unknown. This study aimed to investigate the potential role of neural transmission pathways in the transference of protective signals evoked by PerC. Materials and Methods: Male Sprague-Dawley rats were randomly allocated into 12 groups [sham, middle cerebral artery occlusion (MCAO), MCAO+PerC, MCAO+PerC+vehicle, MCAO+PerC+Capsaicin, MCAO+PerC+sham, MCAO+PerC+denervation, MCAO+PostC, MCAO+PostC+vehicle, MCAO+PostC+sham, MCAO+PostC+Capsaicin, MCAO+PerC+denervation]. The I/R model was established by 90-min occlusion of the right middle cerebral artery and subsequent 24 h reperfusion. Remote conditioning was induced with three cycles of 10 min ischemia/10 min reperfusion of the femoral arteries bilaterally. Nerve block was conducted by local capsaicin treatment of exposed nerves or femoral and sciatic nerve transection. Cerebral infarct volumes were quantified by 2, 3, 4-triphenytetrazolium-chloride stain assay. The phosphorylation of Akt was detected by Western blot. Results: Remote ischemic PerC and PostC therapies reduced the infarct size and attenuated neurological deficits. Blocking the neural transmission pathways abolished the protective effect of PostC but had no effect on PerC. Further, blocking the neural transmission pathways reduced periinfarct Akt activation of PostC but had no effect on PerC. Conclusion: Unlike PostC, neural transmission pathways may not play a significant role in the transference of PerC-induced neuroprotection after I/R injury

CORM-2 inhibits intracerebral hemorrhage-mediated inflammation

Background and purpose: Low-dose of carbon monoxide delivered by CO-releasing molecule-2 (CORM-2) had been confirmed having anti-inflammatory efficacy in some inflammatory diseases. Herein, we assessed the usefulness of CORM-2 in correcting intracerebral hemorrhage (ICH)-mediated inflammation. Methods: Healthy male Sprague Dawley (SD) rats randomly entered into four groups: sham-ICH, ICH, ICH+CORM-2, and ICH+ inactive carbon monoxide releasing molecule 2 (iCORM-2). ICH was induced by 50 μl of autologous arterial blood injected in situ in the rat brain. Neuro-functions of the ICH rats were evaluated with Garcia 18 scores at the 6th, 24th , 48th hou, and the fifthh day post-ICH. And brain tissues surrounding the hematoma area were collected from all ICH rats and assayed with Western blot and immunofluoresence analysis. Results: Neuro-dysfunctions in ICH rats were very severe than those in ICH +CORM-2 rats. Compared to sham group, the levels of HO-1, IKKβ, NF-κB, and TNF-α in ICH group began to elevate at the 6th hour, and reached to peak at the 48th hour post-ICH, all p \u3c 0.05. While in ICH +CORM-2 group, the expressions of IKKβ, NF-κB, and TNF-α were very weaker than that in ICH group at every time points mentioned above; however, this phenomenon was not reproduced in ICH + iCORM-2 group. HO-1 in ICH+CORM-2 group highlighted in perihematomal area with many activated microglia (Iba-1-positive cells) and co-expressed with TNF-α, all of which were diminished at the fifth day post-ICH. Conclusion: CORM-2 may attenuate ICH-mediated inflammation by inhibiting microglial activation, which may involve the IKK/NF-κB pathway. Abbreviations: ICH: intracerebral hemorrhage; CO: carbon monoxide; CORM-2: carbon monoxide releasing molecule-2; iCORM-2: inactive carbon monoxide releasing molecule-2; HO-1: heme oxygenase 1; IKKβ: inhibitor of IκB kinases β; NF-κB: nuclear factor-κB; TNF-α: tumor necrosis factor-α; Iba-1: ionized calcium binding adaptor molecule-1; IκB: inhibitor of NF-κB; iNOS: inducible nitric oxide synthase; Keap1: Kelch-like ECH-associated protein 1; Nrf2: NF-E2-related factor 2; DMSO: dimethylsulfoxide

Safety and efficacy of remote ischemic conditioning in pediatric moyamoya disease patients treated with revascularization therapy

BACKGROUND: Revascularization surgery has been the standard treatment to prevent ischemic stroke in pediatric Moyamoya disease (MMD) patients with ischemic symptoms. However, perioperative complications, such as hyperperfusion syndrome, new infarct on imaging, or ischemic stroke, are inevitable. Remote ischemic conditioning (RIC) is a noninvasive and easy-to-use neuroprotective strategy, and it has potential effects on preventing hyperperfusion syndrome and ischemic infarction. AIMS: The aim of this study is to investigate the safety and efficacy of RIC in pediatric MMD patients undergoing revascularization surgery. METHOD: A total of 60 pediatric MMD patients with one or more ischemic symptoms will be recruited and allocated in 1:1 ratio to the RIC group and sham group, respectively. Both RIC and sham RIC will be performed twice daily for 7 consecutive days before revascularization surgery with different cuff pressures during the ischemia period (50 mmHg over-systolic blood pressure and 30 mmHg). Single photon emission computed tomography will be performed within 7 days preoperatively and 3 months postoperatively, respectively, to evaluate the cerebral perfusion status. Other outcomes, including safety, plasma biomarker, functional outcome, and the incidence of infarction and its size, will also be evaluated. CONCLUSION: This study will provide insights into the preliminary proof of principle, safety, and efficacy of RIC in pediatric MMD patients undergoing revascularization surgery therapy, and this data will provide parameters for future larger scale clinical trials if efficacious

Abdominal Aortic Occlusion and the Inflammatory Effects in Heart and Brain

Background. Abdominal aortic occlusion (AAO) occurs frequently and causes ischemia/reperfusion (I/R) injury to distant organs. In this study, we aimed to investigate whether AAO induced I/R injury and subsequent damage in cardiac and neurologic tissue. We also aimed to investigate the how length of ischemic time in AAO influences reactive oxygen species (ROS) production and inflammatory marker levels in the heart, brain, and serum. Methods. Sixty male C57BL/6 mice were used in this study. The mice were randomly divided into either sham group or AAO group. The AAO group was further subdivided into 1–4 hr groups of aortic occlusion times. The infrarenal abdominal aorta was clamped for 1–4 hr depending on the AAO group and was then reperfused for 24 hr after clamp removal. Serum, hippocampus, and left ventricle tissue samples were then subjected to biochemical and histopathological analyses. Results. AAO-induced I/R injury had no effect on cell necrosis, cell apoptosis, or ROS production. However, serum and hippocampus levels of malondialdehyde (MDA) and lactate dehydrogenase (LDH) increased in AAO groups when compared to sham group. Superoxide dismutase and total antioxidant capacity decreased in the serum, hippocampus, and left ventricle. In the serum, AAO increased the level of inducible nitric oxide synthase (iNOS) and decreased the levels of anti-inflammatory factors (such as arginase-1), transforming growth factor- β1 (TGF-β1), interleukin 4 (IL-4), and interleukin 10 (IL-10). In the hippocampus, AAO increased the levels of tumor necrosis factor (TNF-α), interleukin 1β (IL-1β), interleukin 6 (IL-6), IL-4, and IL-6, and decreased the level of TGF-β1. In the left ventricle, AAO increased the level of iNOS and decreased the levels of TGF-β1, IL-4, and IL-10. Conclusions. AAO did not induce cell necrosis or apoptosis in cardiac or neurologic tissue, but it can cause inflammation in the serum, brain, and heart

Enhanced oxidative stress response and neuroprotection of combined limb remote ischemic conditioning and atorvastatin after transient ischemic stroke in rats

BACKGROUND: Limb remote ischemic conditioning (LRIC) and atorvastatin (AtS) both provide neuroprotection in stroke. We evaluated the enhanced neuroprotective effect of combining these two treatments in preventing ischemia/reperfusion (I/R)-induced cerebral injury in a rat model and investigated the corresponding molecular mechanisms. MATERIALS AND METHODS: Transient cerebral ischemia was induced in Sprague–Dawley male rats by middle cerebral artery occlusion (MCAO) for 90 min followed by reperfusion (I/R). Rats were divided into 5 groups, sham, I/R, I/R + AtS, I/R + LRIC and I/R + AtS + LRIC. Pretreatment with LRIC and/or AtS for 14 days before MCAO surgery. Infarct volume, neurological score, Western blot, immuno-histochemical analyses were performed. RESULTS: The combination of LRIC plus AtS pretreatment decreased infarct volume and inhibited neuronal apoptosis. Combination treatment achieved stronger neuroprotection than monotherapy with LRIC or AtS. These therapies reduced reactive oxygen species production in the peri-ischemia region, associated with significantly increased expression and activation of superoxide dismutase 1, hemeoxygenase 1 and nuclear factor erythroid 2-related factor 2. CONCLUSIONS: Both LRIC and AtS + LRIC treatments conferred neuroprotection in ischemic stroke by reducing brain oxidative stress. AtS plus LRIC is an attractive translational research option due to its ease of use, tolerability, economical, and tremendous neuroprotective potential in stroke

Lire une œuvre du patrimoine : Boucle d'or et les trois ours

Boucle d'or et les trois ours est un conte du patrimoine très apprécié par les enfants, et contrairement à ce qui est communément admis, il ne s'adresse pas exclusivement aux élèves de Petite Section. En effet, ce conte permet un travail très riche basé sur le réseau littéraire dans la mesure où il existe de nombreuses versions de celui-ci. Ainsi, les enseignants de Grande Section peuvent l'utiliser pour travailler la compétence "connaître un conte dans différentes versions ; établir des comparaisons précises entre elles". Pour cela, ils devront familiariser leurs élèves avec le texte-source avant de leur proposer ce travail de comparaison. Ils pourront aussi leur faire découvrir de nombreuses réécritures et détournements qui seront compréhensibles par les élèves que si cette familiarisation a eu lieu. Cela permettra également de faire prendre conscience aux élèves qu'un album peut donner une autre vision du conte, mais aussi qu'un conte peut être continué, ou encore qu'un conte peut être terminé ou enfin qu'un conte peut être repris et modifié. En ce sens, Boucle d'or et les trois ours est un conte du patrimoine qui permet de développer réellement un comportement de lecteur et de construire facilement une véritable culture littéraire chez les élèves