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The recent theory-driven discovery of a class of clathrate hydrides (e.g., CaH6, YH6, YH9, and LaH10) with superconducting critical temperatures (Tc) well above 200 K has opened the prospects for "hot" superconductivity above room temperature under pressure. Recent efforts focus on the search for superconductors among ternary hydrides that accommodate more diverse material types and configurations compared to binary hydrides. Through extensive computational searches, we report the prediction of a unique class of thermodynamically stable clathrate hydrides structures consisting of two previously unreported H24 and H30 hydrogen clathrate cages at megabar pressures. Among these phases, LaSc2H24 shows potential hot superconductivity at the thermodynamically stable pressure range of 167 to 300 GPa, with calculated Tcs up to 331 K at 250 GPa and 316 K at 167 GPa when the important effects of anharmonicity are included. The very high critical temperatures are attributed to an unusually large hydrogen-derived density of states at the Fermi level arising from the newly reported peculiar H30 as well as H24 cages in the structure. Our predicted introduction of Sc in the La-H system is expected to facilitate future design and realization of hot superconductors in ternary clathrate superhydrides.
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BACKGROUND: The effects and risks of endovascular thrombectomy 6 to 24 hours after stroke onset due to basilar-artery occlusion have not been extensively studied. METHODS: In a trial conducted over a 5-year period in China, we randomly assigned, in a 1:1 ratio, patients with basilar-artery stroke who presented between 6 to 24 hours after symptom onset to receive either medical therapy plus thrombectomy or medical therapy only (control). The original primary outcome, a score of 0 to 4 on the modified Rankin scale (range, 0 to 6, with a score of 0 indicating no disability, 4 moderately severe disability, and 6 death) at 90 days, was changed to a good functional status (a modified Rankin scale score of 0 to 3, with a score of 3 indicating moderate disability). Primary safety outcomes were symptomatic intracranial hemorrhage at 24 hours and 90-day mortality. RESULTS: A total of 217 patients (110 in the thrombectomy group and 107 in the control group) were included in the analysis; randomization occurred at a median of 663 minutes after symptom onset. Enrollment was halted at a prespecified interim analysis because of the superiority of thrombectomy. Thrombolysis was used in 14% of the patients in the thrombectomy group and in 21% of those in the control group. A modified Rankin scale score of 0 to 3 (primary outcome) occurred in 51 patients (46%) in the thrombectomy group and in 26 (24%) in the control group (adjusted rate ratio, 1.81; 95% confidence interval [CI], 1.26 to 2.60; P<0.001). The results for the original primary outcome of a modified Rankin scale score of 0 to 4 were 55% and 43%, respectively (adjusted rate ratio, 1.21; 95% CI, 0.95 to 1.54). Symptomatic intracranial hemorrhage occurred in 6 of 102 patients (6%) in the thrombectomy group and in 1 of 88 (1%) in the control group (risk ratio, 5.18; 95% CI, 0.64 to 42.18). Mortality at 90 days was 31% in the thrombectomy group and 42% in the control group (adjusted risk ratio, 0.75; 95% CI, 0.54 to 1.04). Procedural complications occurred in 11% of the patients who underwent thrombectomy. CONCLUSIONS: Among patients with stroke due to basilar-artery occlusion who presented 6 to 24 hours after symptom onset, thrombectomy led to a higher percentage with good functional status at 90 days than medical therapy but was associated with procedural complications and more cerebral hemorrhages. (Funded by the Chinese National Ministry of Science and Technology; BAOCHE ClinicalTrials.gov number, NCT02737189.).
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Arteriopatias Oclusivas , Artéria Basilar , Procedimentos Endovasculares , Acidente Vascular Cerebral , Trombectomia , Humanos , Arteriopatias Oclusivas/complicações , Arteriopatias Oclusivas/tratamento farmacológico , Arteriopatias Oclusivas/mortalidade , Arteriopatias Oclusivas/cirurgia , Artéria Basilar/efeitos dos fármacos , Artéria Basilar/cirurgia , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/etiologia , Isquemia Encefálica/mortalidade , Isquemia Encefálica/cirurgia , Avaliação da Deficiência , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/métodos , Fibrinolíticos/efeitos adversos , Fibrinolíticos/uso terapêutico , Hemorragias Intracranianas/induzido quimicamente , Hemorragias Intracranianas/etiologia , Recuperação de Função Fisiológica , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/cirurgia , Trombectomia/efeitos adversos , Trombectomia/métodos , Fatores de Tempo , Resultado do TratamentoRESUMO
The Finkel-Biskis-Jinkins Osteosarcoma (c-Fos; encoded by FOS) plays an important role in several cardiovascular diseases, including atherosclerosis and stroke. However, the relationship between FOS and venous thromboembolism (VTE) remains unknown. We identified differentially expressed genes in Gene Expression Omnibus dataset, GSE48000, comprising VTE patients and healthy individuals, and analysed them using CIBERSORT and weighted co-expression network analysis (WGCNA). FOS and CD46 expressions were significantly downregulated (FOS p = 2.26E-05, CD64 p = 8.83E-05) and strongly linked to neutrophil activity in VTE. We used GSE19151 and performed PCR to confirm that FOS and CD46 had diagnostic potential for VTE; however, only FOS showed differential expression by PCR and ELISA in whole blood samples. Moreover, we found that hsa-miR-144 which regulates FOS expression was significantly upregulated in VTE. Furthermore, FOS expression was significantly downregulated in neutrophils of VTE patients (p = 0.03). RNA sequencing performed on whole blood samples of VTE patients showed that FOS exerted its effects in VTE via the leptin-mediated adipokine signalling pathway. Our results suggest that FOS and related genes or proteins can outperform traditional clinical markers and may be used as diagnostic biomarkers for VTE.
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Biologia Computacional , MicroRNAs , Neutrófilos , Proteínas Proto-Oncogênicas c-fos , Tromboembolia Venosa , Feminino , Humanos , Masculino , Biomarcadores/sangue , Biomarcadores/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Redes Reguladoras de Genes , MicroRNAs/genética , MicroRNAs/sangue , MicroRNAs/metabolismo , Neutrófilos/metabolismo , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Tromboembolia Venosa/sangue , Tromboembolia Venosa/genética , Tromboembolia Venosa/metabolismoRESUMO
Patients with symptomatic intracranial arterial stenosis (sICAS) suffer embarrassed hemodynamic status and acute ischemic stroke (AIS) recurrence. We aimed to assess the efficacy of remote ischemic conditioning (RIC) on improving this status by evaluating cerebral blood flow (CBF) and cerebral glucose metabolism (CGM) via PET/CT. Adult patients with unilateral sICAS in middle cerebral artery and/or intracranial segment of internal carotid artery-related AIS or transient ischemic attack within 6 months prior to randomization were enrolled. Individuals who received intravenous thrombolysis or endovascular treatment, or sICAS caused by cardiac embolism, small vessel occlusion, or other determined causes were excluded. Twenty-three eligible patients were randomly assigned to standard medical treatment (SMT) (n = 10) or RIC group (n = 13). The RIC protocol consisted of 5 cycles, each for 5-min bilateral upper limb ischemia and 5-min reperfusion period, twice a day, with a total duration of 3 months. Ten healthy volunteers were enrolled as healthy control group. We tested CBF and CGM at the rest stage and the methazolamide-induced stress stage. All patients received PET/CT at baseline and three-month followup. Both CBF and CGM in ipsilateral hemisphere of sICAS patients were significantly decreased at the rest stage and the stress stage (p < .05), which were improved by three-month RIC (p < .05). The lesions decreased notably in RIC group compared to SMT group (p < .05). RIC ameliorated the hemodynamic status and glucose metabolism in regions at high risk of infarction, which might improve the resistance capacity towards ischemic load in sICAS patients.
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Arteriosclerose Intracraniana , AVC Isquêmico , Adulto , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Arteriosclerose Intracraniana/diagnóstico por imagem , Arteriosclerose Intracraniana/terapia , Isquemia , Hemodinâmica , GlucoseRESUMO
Mixed phenotype acute leukemia (MPAL) is a type of acute leukemia in which encompasses mixed features of myeloid, T-lymphoid, and/or B-lymphoid differentiation. Philadelphia chromosome-positive (Ph+) MPAL is a rare subgroup with a poor prognosis and accounts for ï¼1% of adult acute leukemia. Until now, there is still no consensus on how to best treat Ph+ MPAL. Here, we report a 62-year-old male with Ph+ (atypical e13a2 BCR-ABL1 fusion protein) MPAL. This patient presented with recurrent and intense bone pain due to bone marrow necrosis (BMN). Besides, he did not achieve a complete remission for the first two chemotherapies, until he received flumatinib combined with hyper-CVAD (B) (a dose-intensive regimen include methotrexate and cytarabine). To our knowledge, this is the first report to describe the coexistence of BMN and atypical e13a2 BCR-ABL1 transcripts in patients with MPAL. This finding will bring new understandings in the diagnosis and treatment of Ph+ MPAL.
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Medula Óssea , Proteínas de Fusão bcr-abl , Necrose , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Fusão bcr-abl/genética , Medula Óssea/patologia , Leucemia Aguda Bifenotípica/genética , Leucemia Aguda Bifenotípica/patologia , Leucemia Aguda Bifenotípica/tratamento farmacológicoRESUMO
Normobaric hyperoxia (NBO) is a potentially promising stroke treatment strategy that could protect the ischemic penumbra and could be administered as an adjunct before vascular recanalization. However, the efficacy and safety of NBO have not been confirmed by randomized controlled trials. The study aims to assess the efficacy and safety of NBO for ischemic stroke due to large artery occlusion (LVO) of acute anterior circulation among patients who had endovascular treatment (EVT) and were randomized within 6 h from symptom onset. Based on the data of the modified Rankin Scale (mRS) score at 90 days from the normobaric hyperoxia combined with EVT for acute ischemic stroke (OPENS: NCT03620370) trial, 284 patients will be included to achieve a 90% power by using Wilcoxon-Mann-Whitney test and the proportional odds model to calculate the sample size. The study is a prospective, multicenter, blinded, randomized controlled trial. The NBO group is administered with mask oxygen therapy of 10 L/min, while the sham NBO group is with that of 1 L/min. The primary outcome is the mRS score at 90 days. Secondary endpoints include cerebral infarct volume at 24-48 h, functional independence (mRS ≤2) at 90 days, and improvement in neurological function at 24 h. Safety outcomes include 90-day mortality, oxygen-related adverse events, and serious adverse events. This study will indicate whether NBO combined with EVT is superior to EVT alone for acute ischemic stroke caused by LVO in subjects randomized within 6 h from symptom onset and will provide some evidence for NBO intervention as an adjunct to thrombectomy for acute stroke.
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Procedimentos Endovasculares , AVC Isquêmico , Estudos Multicêntricos como Assunto , Oxigenoterapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Recuperação de Função Fisiológica , Humanos , Procedimentos Endovasculares/efeitos adversos , AVC Isquêmico/terapia , AVC Isquêmico/diagnóstico , AVC Isquêmico/fisiopatologia , Estudos Prospectivos , Resultado do Tratamento , Fatores de Tempo , Idoso , Oxigenoterapia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Feminino , Terapia Combinada , Avaliação da Deficiência , China , Estado Funcional , AdultoRESUMO
BACKGROUND: Acute ischemic stroke (AIS) complicating an acute myocardial infarction (AMI) is not uncommon, but can severely worsen the clinical prognosis. This study aimed to investigate whether remote ischemic conditioning (RIC) could provide clinical benefits to patients with AIS complicating AMI. METHODS: Subjects with AIS complicating AMI were recruited in this double-blind, randomized, controlled trial; assigned to the RIC and sham groups; and respectively underwent twice daily RIC and sham RIC for 2 weeks. All subjects received standard medical therapy. The primary endpoint was the rate of major adverse cardiac and cerebrovascular events (MACCEs) within 3 months after enrollment. MACCEs comprise of death from all causes, unstable anginas, AMI, acute ischemic strokes, and transient ischemic attacks. RESULTS: Eighty subjects were randomly assigned; 37 patients in the RIC group and 40 patients in the sham-RIC group completed the 3-month follow-up and were included in the final analysis. Both RIC and sham RIC procedures were well tolerated. At 3-month follow-up, 11 subjects (29.7%) in the RIC group experienced MACCEs compared to 21 (52.5%) in the sham group (hazard ratio [HR], 0.396; 95% confidence interval, 0.187-0.838; adjusted p < 0.05). Six subjects (16.2%) in the RIC group had died at the 3-month follow up, significantly lower than the 15 (37.5%) deaths in the sham group (adjusted HR 0.333; 95% CI 0.126-0.881; p = 0.027). Seventeen subjects (45.9%) in the RIC group and 6 subjects (15.0%) in the sham group achieved functional independence (mRS score ≤ 2) at 3-month follow-up (adjusted OR 12.75; 95% CI 2.104-77.21; p = 0.006). CONCLUSIONS: Among patients with acute ischemic stroke complicating acute myocardial infarction, treatment with remote ischemic conditioning decreased the major adverse cardiac and cerebrovascular events and improved functional outcomes at 90 days. TRIAL REGISTRATION: URL: www. CLINICALTRIALS: gov . Unique identifier: NCT03868007. Registered 8 March 2019.
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AVC Isquêmico , Infarto do Miocárdio , Acidente Vascular Cerebral , Humanos , Infarto do Miocárdio/complicações , Infarto do Miocárdio/terapia , Método Duplo-Cego , Resultado do Tratamento , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapiaRESUMO
Cerebral venous sinus thrombosis (CVST) is a rare type of stroke and standard treatment involves anticoagulation. However, for some special CVST patients who are ineligible for anticoagulation or refractory to conservative treatment, endovascular treatment (EVT) may be an effective option. Mechanical thrombectomy (MT) is a commonly used treatment. Compared with anticoagulation treatment alone, MT may result in additional procedure-related complications, however, many studies have shown that it has a high rate of vessel recanalization and lower incidence of related complications in arterial large vessel occlusion stroke. In addition, the applicability of MT in children, patients with deep cerebral thrombosis, and patients with bleeding before treatment has been reported. MT combined with intravascular thrombolysis (IVT) and other multimodal therapeutic strategies, also has a good curative effect, and further research is needed to compare and optimize different treatment strategies. Owing to the low incidence of CVST, randomized controlled clinical trials with a large sample size to explore the safety and effectiveness of MT are scarce. In addition, devices specifically designed for cerebral venous sinus and effective endovascular therapies are currently not well-established. This article summarizes different endovascular instruments and multimodal therapies for cerebral venous thrombosis. We also discuss the limitations, prospects, prognostic factors, and applications in special cases of interventional thrombectomy.
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Procedimentos Endovasculares , Trombose dos Seios Intracranianos , Trombectomia , Humanos , Trombose dos Seios Intracranianos/terapia , Trombose dos Seios Intracranianos/cirurgia , Trombectomia/métodos , Trombectomia/tendências , Procedimentos Endovasculares/métodos , Procedimentos Endovasculares/tendências , Resultado do Tratamento , Terapia Combinada/métodos , Anticoagulantes/uso terapêutico , Anticoagulantes/administração & dosagem , Terapia Trombolítica/métodosRESUMO
Designing homogeneous networks is considered one typical strategy for solving the problem of strength and toughness conflict of polymer network materials. Experimentalists have proposed the hypothesis of obtaining a structurally homogeneous hydrogel by crosslinking tetra-armed polymers, whose homogeneity was claimed to be verified by scattering characterization and other methods. Nevertheless, it is highly desirable to further evaluate this issue from other perspectives. In this study, a coarse-grained molecular dynamics simulation coupled with a stochastic reaction model is applied to reveal the topological structure of a polymer network synthesized by tetra-armed monomers as precursors. Two different scenarios, distinguished by whether internal cross-linking is allowed, are considered. We introduce the Dijkstra algorithm from graph theory to precisely characterize the network structure. The microscopic features of the network structure, e.g., loop size, dispersity, and size distribution, are obtained via the Dijkstra algorithm. By comparing the two reaction scenarios, Scenario II exhibits an overall more idealized structure. Our results demonstrate the feasibility of the Dijkstra algorithm for precisely characterizing the polymer network structure. We expect this work will provide a new insight for the evaluation and description of gel networks and further help to reveal the dynamic process of network formation.
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Topological regulation of DNA by topoisomerases in cells is very crucial for life. We propose a coarse-grained model to study the catenation process of double-stranded DNA (dsDNA) rings regulated by topoisomerase II (TOP2) and provide a computational method to characterize the topological structures of the Olympic gels obtained. The function of TOP2 in the catenation of dsDNA rings is implicitly fulfilled by operating the length of a stretchable catch bond in the dsDNA ring. After the catenation reaction of initially noncatenated dsDNA rings in the solution, the Olympic gel is obtained and the interlocked topology of the dsDNA rings can be characterized by a computational method derived from the HOMFLY polynomial, based on which the catenation degree and the complexity of catenation are quantified. Detailed dependence of the catenation degree and the complexity of the catenated topology on key parameters, including the size of the transient broken gap and the duration time of the break on the dsDNA ring during operation by TOP2, the initial molar ratio of TOP2 to the dsDNA rings, and the reaction temperature, has been investigated.
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DNA Topoisomerases Tipo II , DNARESUMO
BACKGROUND: Failure of delayed neurological improvement (fDNI) following successful recanalization is a prevalent clinical phenomenon in patients who have experienced acute ischemic stroke (AIS). An investigation into the potential link between markers of systemic inflammation such as platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index known as SII, and the occurrence of fDNI in patients received successful reperfusion was conducted. METHODS: The study included patients diagnosed with AIS who underwent thrombectomy and experienced fDNI, as observed in a prospective study conducted from January 2017 to April 2020. In order to identify predictors of fDNI, we performed multivariable logistic regression and receiver operating characteristic (ROC) curve. RESULTS: Eighty-four patients (23.86%) without early neurological improvement (ENI) experienced DNI, and 268 (76.14%) patients did not show DNI. After adjustment for potential confounders, NLR (adjust OR, 2.131; 95%CI, 1.066-4.259; p = 0.032) and SII (adjust OR, 1.065; 95%CI, 1.001-1.132, p = 0.045) exhibited independent reationship with fDNI independently in multivariate analysis. The areas under AUC of multivariable NLR and SII mode were 0.862 and 0.861, respectively. CONCLUSIONS: The immune-inflammatory biomarkers, including NLR and SII, exhibited associations with DNI in patients without ENI. Further investigations are warranted to elucidate the underlying mechanisms.
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OBJECTIVES: This finite element study aimed to simulate maxillary canine movement during anterior teeth retraction. MATERIALS AND METHODS: Three methods of maxillary canine movement including miniscrew sliding with high hooks (MSH), miniscrew sliding with low hooks (MSL), and the traditional sliding method (TS) without using miniscrews were simulated using three-dimensional finite element analysis. The initial displacement of the maxillary canine, the maximum principal stress of the periodontal ligament and the Von Mises stress were calculated. RESULTS: The distolingual tipping movements of the canine were shown in three movement modes. MSH showed a small tendency to lingual tipping movement and a extrusion movement while MSL had the largest lingual inclination. TS demonstrated a tendency toward distolingual torsion displacement. Compressive stress values were mainly concentrated in the range - 0.003 to -0.006 MPa. For tensile stress, the distribution of MSH and MSL was concentrated in the range 0.005 to 0.009 MPa, TS was mainly distributed about 0.003 MPa. Von Mises equivalent stress distribution showed no significant difference. CONCLUSIONS: The loss of tooth torque was inevitable, irrespective of which method was used to close the extraction space. However, miniscrew application and higher hooks reduced the loss of torque and avoided lingual rotation. CLINICAL RELEVANCE: This study shows that miniscrew implants with different hooks can better control the movement of the maxillary canines. The non-invasive nature of the finite element analysis and its good simulation of dental stress and instantaneous motion trend have a clinical advantage in the analysis of tooth movement.
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Dente Canino , Técnicas de Movimentação Dentária , Dente Pré-Molar , Estresse Mecânico , Análise de Elementos Finitos , Torque , Técnicas de Movimentação Dentária/métodos , MaxilaRESUMO
The issues of fruit waste and safety resulting from rot have spurred a demand for improved packaging systems. Herein, we present highly antibacterial and antioxidative carbon nanodot/silk fibroin (CD/SF) films for fruit preservation. The films are composed of CDs and SF together with a small amount of glycerol via hydrogen bonding, exhibiting outstanding biosafety, transparency, and stretchability. The films effectively integrate key functionalities (atmosphere control, resistance to food-borne pathogens, and antioxidation properties) and can be manufactured in large sizes (about 20 × 30 cm), boasting a transmission rate of 13â¯183 cm3/m2·day for oxygen and 2860 g/m2·day for water vapor, favoring the preservation of fresh fruits. A convenient dip-coating method enables in situ fabrication of films with a thickness of approximately 14 µm directly on the fruits' surface providing comprehensive protection. Importantly, the films are washable and biodegradable. This work presents a promising technology to produce multifunctional and eco-friendly antibacterial packaging systems.
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Fibroínas , Frutas/microbiologia , Antioxidantes/farmacologia , Antibacterianos/farmacologiaRESUMO
High-rate and stable Zn-ion batteries working at low temperatures are highly desirable for practical applications, but are challenged by sluggish kinetics and severe corrosion. Herein, inspired by frost-resistant plants, we report trace hydroxyl-rich electrolyte additives that implement a dual remodeling effect for high-performance low-temperature Zn-ion batteries. The additive with high Zn absorbability not only remodels Zn2+ primary solvent shell by alternating H2 O molecules, but also forms a shielding layer thus remodeling the Zn surface, which effectively enhances fast Zn2+ de-solvation reaction kinetics and prohibits Zn anode corrosion. Taking trace α-D-glucose (αDG) as a demonstration, the electrolyte obtains a low freezing point of -55.3 °C, and the Zn//Zn cell can stably cycle for 2000â h at 5â mA cm-2 under -25 °C, with a high cumulative capacity of 5000â mAh cm-2 . A full battery that stably operates for 10000â cycles at -50 °C is also demonstrated.
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Remote ischemic conditioning (RIC) has been investigated as a promising, safe, and well-tolerated nonpharmacological therapy for cardio-cerebrovascular disease over the past 3 decades; variable results have been found when it is used in cerebrovascular versus cardiovascular disease. For patients with cardiovascular disease, milestone studies suggest that the roles of RIC may be limited. Recently, however, 2 large trials investigating RIC in patients with cerebrovascular disease found promising results, which may reignite the field's research prospects after its setbacks in the cardiovascular field. This perspectives article highlights several important clinical trials of RIC in the cardio-cerebrovascular disease and describes the many challenges of RIC in clinical translation. Finally, based on the available evidence, several promising research directions such as chronic RIC, early initiation in target population, improvement of compliance, better understanding of dosing, and identification of specific biomarkers are proposed and should be investigated before RIC can become applied into clinical practice for patient benefit.
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Doenças Cardiovasculares , Pós-Condicionamento Isquêmico , Humanos , Pós-Condicionamento Isquêmico/métodosRESUMO
BACKGROUND: Experimental studies have demonstrated the neuroprotection of ischemic postconditioning (IPostC) in acute ischemic stroke by attenuating ischemia-reperfusion injury. This study aimed to investigate the safety and tolerability of direct IPostC in both a dog model and patients with acute ischemic stroke treated with thrombectomy. METHODS: The study involved 2 parts. First, IPostC was induced by repeated balloon inflation and deflation in dogs, where a low-pressure balloon was navigated to the anterior spinal artery, and 4 cycles of 5-minute ischemia followed by 5-minute reperfusion were performed. Vascular injuries were assessed using angiography and vascular tissue specimens. Then, a 3+3 dose-escalation trial was conducted in patients with acute ischemic stroke following successful thrombectomy recanalization. Patients received direct IPostC with ischemia and reperfusion durations in progressive increments of 0, 1, 2, 3, 4, and 5 minutes ×4 cycles. Major adverse responses were defined as vessel perforation, rupture, dissection, reocclusion, severe vasospasm, thrombotic events, and rupture of the balloon. RESULTS: IPostC was investigated in 4 dogs. No vessel perforation or rupture, dissection, or vasospasm was observed under the angiography. Only 1 vessel experienced mild injury between the intima and the internal elastic membrane detected on a histopathologic slide. Then, 18 patients were recruited. The duration of IPostC was progressively escalated with no major response happened. No patient experienced agitation, discomfort, or other tolerability issues. Five patients (27.8%) experienced any intracranial hemorrhage after thrombectomy, and 1 (5.6%) was symptomatic. At 3-month follow-up, no patient died, and 9 patients (50%) achieved functional independence. CONCLUSIONS: Direct IPostC inducing by 4 cycles of 5-minute ischemia followed by 5-minute reperfusion is safe, feasible, and tolerable in patients with acute ischemic stroke treated with thrombectomy. Further investigations are needed to determine the safety and preliminary efficacy of direct IPostC. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT05153655.
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Isquemia Encefálica , Pós-Condicionamento Isquêmico , AVC Isquêmico , Traumatismo por Reperfusão , Acidente Vascular Cerebral , Animais , Cães , Traumatismo por Reperfusão/prevenção & controle , Hemorragias Intracranianas , Trombectomia/efeitos adversos , Acidente Vascular Cerebral/cirurgia , Isquemia Encefálica/cirurgia , Resultado do TratamentoRESUMO
Flexible piezoresistive sensors with biological structures are widely exploited for high sensitivity and detection. However, the conventional bionic structure pressure sensors usually suffer from irreconcilable conflicts between high sensitivity and wide detection response range. Herein, a triple periodic minimum surface (TPMS) structure sensor is proposed based on parametric structural design and 3D printing techniques. Upon tailoring of the dedicated structural parameters, the resulting sensors exhibit superior compression durability, high sensitivity, and ultra-high detection range, that enabling it meets the needs of various scenes. As a model system, TPMS structure sensor with 40.5% porosity exhibits an ultra-high sensitivity (132 kPa-1 in 0-5.7 MPa), wide detection strain range (0-31.2%), high repeatability and durability (1000 cycles in 4.41 MPa, 10000 s in 1.32 MPa), and low detection limit (1% in 80 kPa). The stress/strain distributions have been identified using finite element analysis. Toward practical applications, the TPMS structural sensors can be applied to detect human activity and health monitoring (i.e., voice recognition, finger pressure, sitting, standing, walking, and falling down behaviors). The synergistic effects of MWCNTs and MXene conductive network also ensure the composite further being utilized for electromagnetic interference shielding applications.
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Adsorption separation is considered one of the most commonly used gas purification methods. At present, the most widely used adsorption methods are mainly pressure swing adsorption (PSA) and temperature swing adsorption (TSA). In both adsorption methods, a comprehensive understanding of the equilibrium data and the adsorption capacity of the adsorbent is essential for process design and optimization, and the adsorption isotherm can provide a powerful aid in this regard. In this study, through mathematical analysis of the Langmuir isotherm model, the optimal cyclic adsorption conditions and the optimal thermodynamic parameters (entropy change and enthalpy change) under PSA and TSA were obtained. In addition, the isotherm model can be used to predict the isobaric adsorption capacity, and the objective function was established according to the cyclic adsorption capacity and the regeneration sensible heat consumption per unit adsorption capacity to calculate the optimal adsorption/desorption temperatures and optimal cyclic adsorption capacity of various adsorbents.
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Temozolomide (TMZ) is the first-line drug for the clinical treatment of glioblastoma (GBM), but drug resistance limits its treatment benefits. This study was intended to investigate whether propofol could restrict the resistance of GBM cells to TMZ and uncover the underlying mechanisms. Human GBM cell line U251 and TMZ-resistant U251/TMZ cell line were transplanted into mice to construct GBM and TMZ-resistant GBM xenograft tumors. Tumor growth in mice was monitored, and the tumor tissues were collected for biochemical analysis. THP-1 cell differentiated into M0 subtype macrophage using phorbol 12-myristate 13-acetate (PMA). The culture medium of M0 macrophage was collected for treating U251 cells with the presence or absence of propofol or propofol + DMOG (HIF-1α activator). Results showed that propofol significantly enhanced the inhibitory effect of TMZ on tumor growth, macrophage infiltration and inflammation in TMZ-resistant GBM xenograft tumors in vivo. Compared with GBM xenograft tumors, higher expression of HIF-1α, O6-methylguanine-DNA methyltransferase (MGMT), p-p65 and cyclooxygenase 2 (Cox2) was observed in TMZ-resistant GBM xenograft tumors, but propofol co-treatment markedly reduced the expression of these proteins. In in vitro experiments, culture medium from M0 macrophage promoted U251 cell survival, inflammation and expression of HIF-1α, MGMT, p65 and Cox2, whereas inhibited cell apoptosis. However, propofol suppressed the PMA-induced THP-1 M0 macrophage activation, and propofol-treated culture medium from M0 macrophage blocked all the effects of M0 medium on U251 cells. Additionally, DMOG reversed the effect of propofol-treated M0 medium on U251 cells. In conclusion, Propofol restricted TMZ resistance via inhibiting macrophage activation and down-regulating HIF-1α expression in GBM.
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Neoplasias Encefálicas , Glioblastoma , Propofol , Animais , Antineoplásicos Alquilantes/farmacologia , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Ciclo-Oxigenase 2 , Resistencia a Medicamentos Antineoplásicos , Glioblastoma/patologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia , Inflamação/tratamento farmacológico , Ativação de Macrófagos , Camundongos , Propofol/farmacologia , Propofol/uso terapêutico , Temozolomida/farmacologia , Temozolomida/uso terapêutico , Microambiente Tumoral , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Angiogenesis is essential for successful bone defect repair. In normal tissue repair, the physiological inflammatory response is the main regulator of angiogenesis through the activity of macrophages and the cytokines secreted by them. In particular, M2 macrophages which secrete high levels of PDGF-BB are typically considered to promote angiogenesis. A hexapeptide [WKYMVm, (Trp-Lys-Tyr-Met-Val-D-Met-NH2)] has been reported to modulate inflammatory activities. However, the underlying mechanisms by which WKYMVm regulates macrophages remain unclear. In this study, the possible involvement by which WKYMVm induces the polarization of macrophages and affects their behaviors was evaluated. In vitro results showed that macrophages were induced to an M2 rather than M1 phenotype and the M2 phenotype was enhanced by WKYMVm through activation of the JAK1/STAT6 signaling pathway. It was also found that WKYMVm played an important role in the PDGF-BB production increase and proangiogenic abilities in M2 macrophages. Consistent with the results in vitro, the elevated M2/M0 ratio induced by WKYMVm enhanced the formation of new blood vessels in a femoral defect mouse model. These findings suggest that WKYMVm could be a promising alternative strategy for angiogenesis in bone repair by inducing M2 macrophage polarization.