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Lightweight materials with high strength and long cyclic lifespan are greatly demanded in practical applications, yet these properties are usually mutually exclusive. Here, we present a strong, lightweight, highly deformation-tolerant, and fatigue-resistant carbon nanotube (CNT) composite enabled by an amorphous/crystalline heterophase carbon shell. In particular, we obtain nanocrystallites with CNT-induced crystalline orientation uniformly embedded within an amorphous matrix by controlled thermal annealing. The heterophase carbon shell effectively alleviates the stress concentration and inhibits crack propagation, which renders our composite superior mechanical properties and high fatigue resistance (106 compression cycles at 20% strain with high stress of 144 kPa, or 5 × 105 cycles at 50% strain with stress up to 260 kPa). This study provides a deep understanding of amorphous-crystalline phase transition and insight into utilizing phase engineering to design and develop other high-performance functional materials such as structural materials and catalysis.
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ABSTRACT: Aneurysms are localized dilations of blood vessels, which can expand to 50% of the original diameter. They are more common in cardiovascular and cerebrovascular vessels. Rupture is one of the most dangerous complications. The pathophysiology of aneurysms is complex and diverse, often associated with progressive vessel wall dysfunction resulting from vascular smooth muscle cell death and abnormal extracellular matrix synthesis and degradation. Multiple studies have shown that long noncoding RNAs (lncRNAs) play a significant role in the progression of cardiovascular and cerebrovascular diseases. Therefore, it is necessary to find and summarize them. LncRNAs control gene expression and disease progression by regulating target mRNA or miRNA and are biomarkers for the diagnosis and prognosis of aneurysmal cardiovascular and cerebrovascular diseases. This review explores the role, mechanism, and clinical value of lncRNAs in aneurysms, providing new insights for a deeper understanding of the pathogenesis of cardiovascular and cerebrovascular aneurysms.
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Aneurisma Intracraniano , Músculo Liso Vascular , Miócitos de Músculo Liso , Fenótipo , RNA Longo não Codificante , Humanos , Músculo Liso Vascular/patologia , Músculo Liso Vascular/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Aneurisma Intracraniano/genética , Aneurisma Intracraniano/patologia , Aneurisma Intracraniano/metabolismo , Aneurisma Intracraniano/fisiopatologia , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Animais , Regulação da Expressão Gênica , Aneurisma/genética , Aneurisma/patologia , Aneurisma/metabolismo , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/patologia , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Transdução de SinaisRESUMO
Actuators based on shape memory polymers and composites incorporating nanomaterial additives have been extensively studied; achieving both high output stress and precise shape change by low-cost, scalable methods is a long-term-desired yet challenging task. Here, conventional polymers (polyurea) and carbon nanotube (CNT) fillers are combined to fabricate reinforced composite fibers with exceptional actuation performance, by a wet-spinning method amenable for continuous production. It is found that a thermal-induced shrinkage step could obtain densified strong fibers, and the presence of CNTs effectively promotes the tensile orientation of polymer molecular chains, leading to much improved mechanical properties. Consequently, the CNT/ polyurea composite fibers exhibit stresses as high as 33 MPa within 0.36 s during thermal actuation, and stresses up to 22 MPa upon electrical stimulation enabled by the built-in conductive CNT networks. Utilizing the flexible thin fibers, various shape change behavior are also demonstrated including the conversion between different structures/curvatures, and recovery of predefined simple patterns. This high-performance composite fibers, capable of both thermal and electrical actuation and produced by low-cost materials and fabrication process, may find many potential applications in wearable devices, robotics, and biomedical areas.
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The effective separation of aromatic and aliphatic hydrocarbons remains a notable challenge in the petrochemical industry. Herein, we report a self-healing three-dimensional B â N-based hydrogen-bonded organic framework (HOF), BN-HOF-1, constructed from discrete B â N inclusive dimers through weak C-H···F and C-H···N hydrogen-bonding interactions. To make use of the specific recognition of the B â N inclusive dimers for the toluene molecules and the reversible ad/desorption nature of this novel HOF, BN-HOF-1 can exclusively recognize and separate toluene from the mixtures of toluene-methylcyclohexane, thus generating 99.6% pure toluene from its mixtures after gentle heating, the recorded value among any reported materials for toluene purification. After the toluene molecules were released from the framework, it becomes the condensed BN-HOF-1a, which can be further reused for the highly selective recognition and purification of toluene from its binary mixtures, through the reversible structural recovery back to BN-HOF-1. Single-crystal X-ray diffraction and molecular modeling studies reveal that the high specific toluene recognition is attributed to the complementary electrostatic potential between the host B â N inclusive dimers and the guest toluene, while the self-healing and recovery nature of this HOF is attributed to weak intermolecular hydrogen-bonding interactions.
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Central nervous system (CNS) diseases, such as stroke, traumatic brain injury, dementia, and demyelinating diseases, are generally characterized by high morbidity and mortality, which impose a heavy economic burden on patients and their caregivers throughout their lives as well as on public health. The occurrence and development of CNS diseases are closely associated with a series of pathophysiological changes including inflammation, blood-brain barrier disruption, and abnormal coagulation. Endothelial glycocalyx (EG) plays a key role in these changes, making it a novel intervention target for CNS diseases. Herein, we review the current understanding of the role of EG in common CNS diseases, from the perspective of individual pathways/cytokines in pathophysiological and systematic processes. Furthermore, we emphasize the recent developments in therapeutic agents targeted toward protection or restoration of EG. Some of these treatments have yielded unexpected pharmacological results, as previously unknown mechanisms underlying the degradation and destruction of EG has been brought to light. Furthermore, the anti-inflammatory, anticoagulative, and antioxidation effects of EG and its protective role exerted via the blood-brain barrier have been recognized.
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RATIONALE AND OBJECTIVES: This study explored the intratumor heterogeneity (ITH) of esophageal squamous cell carcinoma (ESCC) using computed tomography (CT) and investigated the value of CT-based ITH in predicting the response to immune checkpoint inhibitor (ICI) plus chemotherapy in patients with ESCC. MATERIALS AND METHODS: This retrospective study included 416 patients with ESCC who received ICI plus chemotherapy at two independent hospitals between January 2019 and July 2022. Multiparametric CT features were extracted from ESCC lesions and screened using hierarchical clustering and dimensionality reduction algorithms. Logistic regression and machine learning models based on selected features were developed to predict treatment response and validated in separate datasets. ITH was quantified using the score calculated by the best-performing model and visualized through feature clustering and feature contribution heatmaps. A gene set enrichment analysis (GSEA) was performed to identify the biological pathways underlying the CT-based ITH. RESULTS: The extreme gradient boosting model based on CT-derived ITH had higher discriminative power, with areas under the receiver operating characteristic curve of 0.864 (95% confidence interval [CI]: 0.774-0.954) and 0.796 (95% CI: 0.698-0.893) in the internal and external validation sets. The CT-based ITH pattern differed significantly between responding and non-responding patients. The GSEA indicated that CT-based ITH was associated with immunity-, keratinization-, and epidermal cell differentiation-related pathways. CONCLUSION: CT-based ITH is an effective biomarker for identifying patients with ESCC who could benefit from ICI plus chemotherapy. Immunity-, keratinization-, and epidermal cell differentiation-related pathways may influence the patient's response to ICI plus chemotherapy.
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Stimulus-responsive polymer-based actuators are extensively studied, with the challenging goal of achieving comprehensive performance metrics that include large output stress and strain, fast response, and versatile actuation modes. The design and fabrication of nanocomposites offer a promising route to integrate the advantages of both polymers and nanoscale fillers, thus ensuring superior performance. Here, it is started from a three-dimensional (3D) porous sponge to fabricate a mutually interpenetrated nanocomposite, in which the embedded carbon nanotube (CNT) network undergoes collective deformation with the shape memory polymer (SMP) matrix during large-degree stretching and releasing, increases junction density with polymer chains and enhances molecular orientation. These features result in substantial improvement of the overall mechanical properties and during thermally actuated contraction, the bulk SMP/CNT composites exhibit output stresses up to 19.5 ± 0.97 MPa and strains up to 69%, accompanied by a rapid response and high energy density, exceeding the majority of recent reports. Furthermore, electrical actuation is also demonstrated via uniform Joule heating across the self-percolated CNT network. Applications such as low-temperature thermal actuated vascular stent and wound dressing are explored. These findings lay out a universal blueprint for developing robust and highly deformable SMP/CNT nanocomposite actuators with broad potential applications.
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BACKGROUND: Direct carotid-cavernous fistulas (dCCFs) involve the abnormal shunting of blood between the internal carotid artery and the cavernous sinus. The use of covered stents (CSs) has been reported for the treatment of complex carotid artery lesions. However, the efficacy and safety of CS treatment for dCCFs remain controversial. Thus, we performed a systematic review and meta-analysis to evaluate these efficacy and safety endpoints. METHODS: A systematic literature review was performed by comprehensively searching the Medline, Embase, and Web of Science databases to identify studies that were related to CS treatment for dCCFs. Then, a meta-analysis was conducted to pool the efficacy and safety outcomes from these studies based on perioperative and follow-up data. RESULTS: Fourteen noncomparative studies enrolling 156 patients with 160 dCCFs met the inclusion criteria. When analyzing perioperative outcomes, the technical success rate was 98.5% [95% confidence interval (CI), 0.948; 1.000], and the immediate complete occlusion rate was 90.9% (95% CI, 0.862; 0.959). Vasospasm and dissection occurred in 32.2% (95% CI, 0.238; 0.463) and 0.1% (95% CI, 0.000; 0.012) of patients, respectively. The in-stent acute thrombus formation rate was 0.1% (95% CI, 0.000; 0.013). Postoperatively, the mortality rate was 0.1% (95% CI, 0.000; 0.013). Based on available follow-up data, the final complete occlusion and parent artery stenosis rates were 99.3% (95% CI, 0.959; 1.000) and 18.6% (95% CI, 0.125; 0.277), respectively. CONCLUSIONS: CS placement can be used to safely and effectively treat dCCFs. These results provide a reference for future clinical trials.
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Fístula Carótido-Cavernosa , Stents , Humanos , Fístula Carótido-Cavernosa/cirurgia , Fístula Carótido-Cavernosa/terapia , Resultado do Tratamento , Procedimentos Endovasculares/métodosRESUMO
BACKGROUND: The effects of genes on the development of intracranial aneurysms (IAs) remain to be elucidated, and reliable blood biomarkers for diagnosing IAs are yet to be established. This study aimed to identify genes associated with IAs pathogenesis and explore their diagnostic value by analyzing IAs datasets, conducting vascular smooth muscle cells (VSMC) experiments, and performing blood detection. METHODS: IAs datasets were collected and the differentially expressed genes were analyzed. The selected genes were validated in external datasets. Autophagy was induced in VSMC and the effect of selected genes was determined. The diagnostic value of selected gene on the IAs were explored using area under curve (AUC) analysis using IAs plasma samples. RESULTS: Analysis of 61 samples (32 controls and 29 IAs tissues) revealed a significant increase in expression of ADORA3 compared with normal tissues using empirical Bayes methods of "limma" package; this was further validated by two external datasets. Additionally, induction of autophagy in VSMC lead to upregulation of ADORA3. Conversely, silencing ADORA3 suppressed VSMC proliferation and autophagy. Furthermore, analysis of an IAs blood sample dataset and clinical plasma samples demonstrated increased ADORA3 expression in patients with IA compared with normal subjects. The diagnostic value of blood ADORA3 expression in IAs was moderate when analyzing clinical samples (AUC: 0.756). Combining ADORA3 with IL2RB or CCR7 further enhanced the diagnostic ability for IAs, with the AUC value over 0.83. CONCLUSIONS: High expression of ADORA3 is associated with IAs pathogenesis, likely through its promotion of VSMC autophagy. Furthermore, blood ADORA3 levels have the potential to serve as an auxiliary diagnostic biomarker for IAs.
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Aneurisma Intracraniano , Humanos , Aneurisma Intracraniano/diagnóstico , Aneurisma Intracraniano/genética , Aneurisma Intracraniano/patologia , Teorema de Bayes , Perfilação da Expressão Gênica , Transcriptoma , BiomarcadoresRESUMO
Low viability of seed cells and the concern about biosafety restrict the application of cell-based tissue-engineered bone (TEB). Exosomes that bear similar bioactivities to donor cells display strong stability and low immunogenicity. Human umbilical cord mesenchymal stem cells-derived exosomes (hUCMSCs-Exos) show therapeutic efficacy in various diseases. However, little is known whether hUCMSCs-Exos can be used to construct TEB to repair bone defects. Herein, PM-Exos and OM-Exos were separately harvested from hUCMSCs which were cultured in proliferation medium (PM) or osteogenic induction medium (OM). A series of in-vitro studies were performed to evaluate the bioactivities of human bone marrow mesenchymal stem cells (hBMSCs) when co-cultured with PM-Exos or OM-Exos. Differential microRNAs (miRNAs) between PM-Exos and OM-Exos were sequenced and analyzed. Furthermore, PM-Exos and OM-Exos were incorporated in 3D printed tricalcium phosphate scaffolds to build TEBs for the repair of critical-sized calvarial bone defects in rats. Results showed that PM-Exos and OM-Exos bore similar morphology and size. They expressed representative surface markers of exosomes and could be internalized by hBMSCs to promote cellular migration and proliferation. OM-Exos outweighed PM-Exos in accelerating the osteogenic differentiation of hBMSCs, which might be attributed to the differentially expressed miRNAs. Furthermore, OM-Exos sustainably released from the scaffolds, and the resultant TEB showed a better reparative outcome than that of the PM-Exos group. Our study found that exosomes isolated from osteogenically committed hUCMSCs prominently facilitated the osteogenic differentiation of hBMSCs. TEB grafts functionalized by OM-Exos bear a promising application potential for the repair of large bone defects.
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Purification of ethylene (C2H4) as the most extensive and output chemical, from complex multi-components is of great significance but highly challenging. Herein we demonstrate that precise pore structure tuning by controlling the network hydrogen bonds in two highly-related porous coordination networks can shift the efficient C2H4 separation function from C2H2/C2H4/C2H6 ternary mixture to CO2/C2H2/C2H4/C2H6 quaternary mixture system. Single-crystal X-ray diffraction revealed that the different amino groups on the triazolate ligands resulted in the change of the hydrogen bonding in the host network, which led to changes in the pore shape and pore chemistry. Gas adsorption isotherms, adsorption kinetics and gas-loaded crystal structure analysis indicated that the coordination network Zn-fa-atz (2) weakened the affinity for three C2 hydrocarbons synchronously including C2H4 but enhanced the CO2 adsorption due to the optimized CO2-host interaction and the faster CO2 diffusion, leading to effective C2H4 production from the CO2/C2H2/C2H4/C2H6 mixture in one step based on the experimental and simulated breakthrough data. Moreover, it can be shaped into spherical pellets with maintained porosity and separation performance.
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Necroptosis is known to play an important role in the pathophysiology of cerebral ischemia; however, its role in the occurrence of secondary thalamic injury after focal cerebral infarction and the mechanism about how mixed lineage kinase domain-like (MLKL) executes necroptosis in this pathophysiology are still unclear. In this study, Sprague-Dawley rats were subjected to distal branch of middle cerebral artery occlusion (dMCAO). The expression of MLKL, connexin 43 (Cx43) and Von Hippel-Lindau (VHL) in vitro and in vivo were assessed by Western blot. Bioinformatic methods were used to predict the potential binding sites where MLKL interacted with Cx43, and the ubiquitination degradation of Cx43 regulated by VHL. The interactions among MLKL, Cx43, VHL, and Ubiquitin were assessed by immunoprecipitation. Dye uptake assay were used to examine the Cx43 hemichannels. Intracellular Ca2+ concentration was measured using Fluo-4 AM. Overexpression and site-directed mutagenesis studies were used to study the mechanisms by which MLKL regulates Cx43 ubiquitinational degradation to mediate neuronal necroptosis. We found that MLKL and Cx43 were upregulated in the ventral posterolateral nucleus (VPN) of the ipsilateral thalamus after dMCAO. In the in vitro experiments MLKL and Cx43 were upregulated after TSZ-mediated necroptosis in SH-SY5Y cells. The interaction between MLKL and Cx43 inhibited the K48-linked ubiquitination of Cx43 in necroptotic SH-SY5Y cells. VHL is an E3 ubiquitin ligase for Cx43, and MLKL competes with VHL for binding to Cx43. Interaction of MLKL Ser454 with Cx43 can trigger the opening of Cx43 hemichannels, causing increased intracellular Ca2+, and cell necroptosis. This innovative study at animal models, cellular, and molecular levels is anticipated to clarify the roles of MLKL and Cx43 in thalamic damage after focal cortical infarction. Our findings may help identify novel targets for neurological recovery after cortical infarction.
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Conexina 43 , Neuroblastoma , Animais , Humanos , Ratos , Infarto Cerebral , Necroptose , Neuroblastoma/metabolismo , Proteínas Quinases/metabolismo , Ratos Sprague-Dawley , Tálamo/metabolismoRESUMO
Up to now, impaired bone regeneration severely affects the healing of bone fractures, thus bringing tremendous suffering to patients. As a vital mediator between inflammatory response and bone regeneration, M2 macrophage-derived exosomes (M2-Exos) attenuate inflammation and promote tissue repair. However, due to a lack of specific targeting property, M2-Exos will be rapidly eliminated after systematic administration, thus compromising their effectiveness in promoting bone regeneration. To solve this hurdle, we initially harvested and characterized the pro-osteogenic properties of M2-Exos. A bone marrow mesenchymal stem cell (BMSC)-specific aptamer was synthesized and 3-way junction (3WJ) RNA nanoparticles were applied to conjugate the BMSC-specific aptamer and M2-Exos. In vitro assays revealed that M2-Exos bore the representative features of exosomes and significantly promoted the proliferation, migration, and osteogenic differentiation of BMSCs. 3WJ RNA nanoparticles-aptamer functionalized M2-Exos (3WJ-BMSCapt/M2-Exos) maintained the original physical characteristics of M2-Exos, but bore a high specific binding ability to BMSCs. Furthermore, when being systemically administered in the mice model with femoral bone fractures, these functionalized M2-Exos mainly accumulated at the bone fracture site with a slow release of exosomal cargo, thereby significantly accelerating the healing processes compared with the M2-Exos group. Our study indicated that the 3WJ-BMSCapt/M2-Exos with BMSCs targeting ability and controlled release would be a promising strategy to treat bone fractures.
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Aptâmeros de Nucleotídeos , Exossomos , Fraturas Ósseas , Camundongos , Animais , Humanos , Osteogênese , Exossomos/metabolismo , Aptâmeros de Nucleotídeos/metabolismo , Macrófagos , Fraturas Ósseas/metabolismo , RNA/metabolismoRESUMO
Aerogels and foams are promising electrode materials owing to their lightweight, high porosity, and large surface area for creating abundant active/catalytic sites. Tailoring their porous structure is essential toward maximum electrode performance yet remains challenging in the field. Here, by modifying a pristine carbon nanotube (CNT) sponge with random internal distribution, we present a CNT platform consisting of regular, orthogonally intercrossed through-channels centered at a suitable lateral size (around 5 µm), with low tortuosity and enhanced electrochemical kinetics under predefined compression. Our CNT platforms, grafted by bifunctional transitional metal hydroxide catalyst, overcome considerable challenges of both long cycle life and high rates simultaneously, serving as Li-O2 cathodes and achieving lifetime of 500 cycles at 0.5 mA cm-2 (275 cycles even at 1 mA cm-2) and also displaying high areal capacity (27 mA h cm-2), which are superior to most of the recently reported porous electrodes based on various materials. The mechanism involving fast triple-phase transport and reversible discharge product deposition, enabled by catalyst-loaded orthogonal channels, has been disclosed. Such structure-tailored robust CNT platforms could find many applications in electrochemical catalysis and energy storage systems.
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The mechanisms underlying secondary brain injury in remote areas remains unclear. This study aimed to investigate the relationship between vascular tortuosity and thalamic volume. METHODS: In this study, we retrospectively analyzed sixty-five patients with unilateral middle cerebral artery occlusion (MCAO) who underwent magnetic resonance angiography. We compared the vascular tortuosity in patients with MCAO and controls, and analyzed the relationship between vascular tortuosity and thalamic volume. RESULTS: Compared with controls, the MCAO group exhibited a significantly smaller thalamus volume on the affected side (5874 ± 183 mm3 vs. 5635 ± 383 mm3, p < 0.0001). The vascular tortuosity of the posterior cerebral artery (PCA) was higher in the MCAO group than in the controls (82.8 ± 17.3 vs. 76.7 ± 17.3, p = 0.040). Logistic regression analysis revealed that PCA tortuosity was an independent risk factor for reduced thalamic volume after MCAO (p = 0.034). In the subgroup analysis, only the 4-7-day group was not statistically different in thalamic volume between the MCAO and control groups. In the MCAO group, patients older than 60 years and female patients had a more tortuous PCA. CONCLUSION: Reduced thalamic volume after MCAO was associated with a tortuous PCA. After MCAO, PCA tortuosity increased more significantly in patients aged >60 years and in female patients.
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Objective: This study aimed to investigate the feasibility and clinical efficacy of endovascular recanalization in patients with chronic internal carotid artery occlusion (CICAO) and explore the application value of computed tomography perfusion (CTP) in endovascular recanalization. Methods: This non-randomized controlled study included 41 patients with CICAO. All patients received active medical treatment. In this study, patients with successful endovascular recanalization and those who refused endovascular recanalization were included in the recanalization and medication groups, respectively. Before and 90 days after treatment, cognitive function was evaluated using the Montreal Cognitive Function Assessment, and neurological function was evaluated using the National Institutes of Health Stroke Scale and modified Rankin scale. For patients with successful endovascular recanalization, brain CTP imaging was performed to evaluate hemodynamic changes in patients with CICAO before and three days after treatment. Results: Overall, 41 symptomatic patients with CICAO were included, and 20 patients received endovascular recanalization therapy, with a success rate of 60% (12/20). The perioperative complication rate was 15% (3/20); there were no events such as hyperperfusion, distal embolism, vascular rupture, or cerebral hemorrhage, and no stroke-related or death-related events. Patients were divided into a medication group (n=21) and recanalization group (n=12). After 90 days of follow-up, patients in the recanalization group showed greater improvement in overall cognitive and neurological function. In addition, successful endovascular recanalization significantly improved cerebral blood perfusion on the occluded side of patients with CICAO. Conclusion: Successful recanalization can effectively improve the overall cognitive and neurological functions of patients in the short term. CTP can be used to quantitatively evaluate not only the cerebral hemodynamic changes after internal carotid artery occlusion but also the improvement of cerebral blood perfusion after successful endovascular recanalization, which provides a reliable method for postoperative follow-up.
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BACKGROUND: Although transcranial magnetic stimulation (TMS)-based closed-loop (TBCL) modality was seldom recommended for functional restoring following spinal cord injury (SCI), several studies recently came to a positive suggestion. AIM: To explore the independent factors which influence activity of daily living (ADL) gain, and systematically investigate the efficacy of TBCL for ADL gain. DESIGN: A retrospective observational study. SETTING: The First Affiliated Hospital of Guangxi Medical University. POPULATION: SCI patients with neurological dysfunction. METHODS: A total of 768 patients who received TBCL (N.=548) or sole rehabilitation (SR, N.=220) were enrolled. Analysis on propensity score matching was also performed. Finally, the cumulative inefficiencies between TBCL and SR within entire patient population, matched-patients as well as subgroup on per SCI clinical characteristics were performed. RESULTS: Multivariate analysis showed that thoracolumbar injury, single/double injury, incomplete injury, no neurogenic bladder, no neurogenic intestinal and no respiratory disorder, as well as TBCL strategy were independent positive factors for ADL gain. Meanwhile, TBCL strategy was the outstanding positive factor. TBCL caused a lower cumulative inefficiency over SR at 1, 90 and 180 days (83.2% vs. 86.8%, 54.0% vs. 63.6%, and 38.3% vs. 50.9%, respectively; all P<0.05). Propensity matching also found TBCL caused a lower cumulative inefficiency over SR after 1, 90 and 180 days (82.4% vs. 86.4%, 51.1% vs. 62.5%, and 33.5% vs. 49.4%, respectively; all P<0.05). Subgroup analysis showed that TBCL caused a greater ADL gain regardless of injured site, segments of injury and injured extent, as well as whether concurrent with neurogenic bladder, neurogenic intestinal and respiratory disorder (all P<0.05). Further, TBCL was more effective in 180-days overall ADL gain within each subgroup (all P<0.05), except the subgroup whether concurrent with respiratory disorder (P>0.05). CONCLUSIONS: Our study indicates that TBCL strategy was the most outstanding independent positive factors for ADL gain. Further, TBCL is a better choice than SR in ADL gain for SCI-relevant neurological dysfunctions in case of adequate stimuli distance and individual temperature, regardless of discrepancy of clinical feature. CLINICAL REHABILITATION IMPACT: This study helps to improve everyday management for rehabilitative intervention on SCI. For another thing, the present study may be good for neuromodulation practice on function restoring in SCI rehabilitation clinics.
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Traumatismos da Medula Espinal , Bexiga Urinaria Neurogênica , Humanos , Atividades Cotidianas , Estudos Retrospectivos , Estimulação Magnética Transcraniana , Pontuação de Propensão , China , Traumatismos da Medula Espinal/reabilitação , Bexiga Urinaria Neurogênica/etiologiaRESUMO
No definitive blood markers of DWI-FLAIR mismatch, a pivotal indicator of salvageable ischemic penumbra brain tissue, are known. We previously reported that CDC42 and RHOA are associated with the ischemic penumbra. Here, we investigated whether plasma CDC42 and RHOA are surrogate markers of DWI-FLAIR mismatch. Sixteen cynomolgus macaques (3 as controls and 13 for the stroke model) were included. Guided by digital subtraction angiography (DSA), a middle cerebral artery occlusion (MCAO) model was established by occluding the middle cerebral artery (MCA) with a balloon. MRI and neurological deficit scoring were performed to evaluate postinfarction changes. Plasma CDC42 and RHOA levels were measured by enzyme-linked immunosorbent assay (ELISA). The stroke model was successfully established in eight monkeys. Based on postinfarction MRI images, experimental animals were divided into a FLAIR (-) group (N = 4) and a FLAIR (+) group (N = 4). Plasma CDC42 in the FLAIR (-) group showed a significant decrease compared with that in the FLAIR (+) group (p < 0.05). No statistically significant difference was observed for plasma RHOA. The FLAIR (-) group showed a milder neurological function deficit and a smaller infarct volume than the FLAIR (+) group (p < 0.05). Therefore, plasma CDC42 might be a new surrogate marker for DWI-FLAIR mismatch.
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Intracerebral haemorrhage (ICH) is a catastrophic subtype of stroke with severe morbidity and mortality. However, little progress has been made in the subsequent secondary injury. Artesunate, a water-soluble semi-synthetic derivative of artemisinin, exhibits remarkable pharmacological effects on anti-neuroinflammation. However, the effects of artesunate on ICH remain unknown. In the present study, haemoglobin (Hb) treatment in BV2 cell and collagenase type IV intracerebroventricular injection in Sprague-Dawley rats were used to establish in vitro and in vivo ICH models, respectively. For in vivo, the neurological scores, haematoma volume, brain oedema, inflammatory factors and iron deposition were evaluated. Besides, lipopolysaccharide (LPS) was used in in vitro to polarize BV2 cell to M1 phenotype. Cell viability, cellular reactive oxygen species (ROS), Fe2+ concentration, and lipid peroxidation levels, ferroptosis-associated proteins and mRNA, morphological of mitochondria were measured in vitro. Additionally, the AMP-activated protein kinase (AMPK)/mammalian/mechanistic target of rapamycin (mTOR) pathway were measured by western blot and immunofluorescence staining. The present in vivo results indicated that artesunate significantly ameliorated neurological deficits, haematoma volume and brain oedema in ICH rats. Besides, artesunate suppressed the M1-microglia relative inflammatory factors and up-regulated iron deposition. For in vitro, artesunate significantly selectively decreased the viability of LPS-stimulated BV2 cell. Furthermore, ROS and lipid peroxidation levels were up-regulated. And the glutathione peroxidase 4 (GPX4) were silenced via the AMPK/mTORC1 axis. Our finding supports that artesunate ameliorates the ICH secondary injury both in vitro and in vivo by inducing ferroptosis in microglia and further inhibiting inflammation mainly through the AMPK/mTORC1/GPX4 pathway. This finding may provide a novel target for ICH treatment.
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Edema Encefálico , Lesões Encefálicas , Ferroptose , Animais , Ratos , Proteínas Quinases Ativadas por AMP/metabolismo , Artesunato/farmacologia , Artesunato/metabolismo , Edema Encefálico/tratamento farmacológico , Lesões Encefálicas/complicações , Lesões Encefálicas/metabolismo , Hemorragia Cerebral/tratamento farmacológico , Hemorragia Cerebral/complicações , Hemorragia Cerebral/metabolismo , Hematoma/complicações , Hematoma/metabolismo , Inflamação/metabolismo , Ferro/farmacologia , Lipopolissacarídeos/farmacologia , Mamíferos/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Microglia/metabolismo , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismoRESUMO
Epidemics caused by pathogens in recent years have created an urgent need for energetic biocidal agents with the capacity of detonation and releasing bactericides. Herein we present a new type of energetic biocidal agents based on a series of iodine-rich molecular perovskites, (H2dabco)M(IO4)3 (dabco = 1,4-diazabicyclo[2.2.2]octane, M = Na+/K+/Rb+/NH4 + for DAI-1/2/3/4) and (H2dabco)Na(H4IO6)3 (DAI-X1). These compounds possess a cubic perovskite structure, and notably have not only high iodine contents (49-54 wt%), but also high performance in detonation velocity (6.331-6.558 km s-1) and detonation pressure (30.69-30.88 GPa). In particular, DAI-4 has a very high iodine content of 54.0 wt% and simultaneously an exceptional detonation velocity up to 6.558 km s-1. As disclosed by laser scanning confocal microscopy observation and a standard micro-broth dilution method, the detonation products of DAI-4 exhibit a broad-spectrum bactericidal effect against bacteria (E. coli, S. aureus, and P. aeruginosa). The advantages of easy scale-up synthesis, low cost, high detonation performance, and high iodine contents enable these periodate-based molecular perovskites to be highly promising candidates for energetic biocidal agents. Electronic Supplementary Material: Supplementary material is available in the online version of this article at 10.1007/s40843-022-2257-6.