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The application of lithium metal anode in all-solid-state batteries has the potential to achieve both high energy density and safety performance. However, the presence of serious dendrite issues hinders this potential. Here, the ion transport pathways and orientation of dendrite growth are regulated by utilizing the differences of ionic conductivity in heterogeneous electrolytes. The in situ formed Li-Ge alloy phases from the spontaneous reaction between Li10GeP2S12 and the attracted dendrites greatly enhance the ability to resist dendrite growth. As an outcome, the heterogeneous electrolyte achieves a high critical current density of 2.1 mA cm-2 and long-term stable symmetrical battery operation (0.3 mA cm-2 for 17 000 h and 1.0 mA cm-2 for 2000 h). Besides, due to the superior interfacial stability and low interface impedance between the heterogeneous electrolyte and lithium anode, the Li||LiNi0.8Co0.1Mn0.1O2 full battery exhibits great cycling stability (80.5% after 500 cycles at 1.0 mA cm-2) and rate performance (125.4 mAh g at 2.0 mA cm-2). This work provides a unique strategy of interface regulation via heterogeneous electrolytes design, offering insights into the development of state-of the-art all-solid-state batteries.
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All-solid-state lithium batteries (ASSBs) have received increasing attentions as one promising candidate for the next-generation energy storage devices. Among various solid electrolytes, sulfide-based ASSBs combined with layered oxide cathodes have emerged due to the high energy density and safety performance, even at high-voltage conditions. However, the interface compatibility issues remain to be solved at the interface between the oxide cathode and sulfide electrolyte. To circumvent this issue, we propose a simple but effective approach to magic the adverse surface alkali into a uniform oxyhalide coating on LiNi0.8Co0.1Mn0.1O2 (NCM811) via a controllable gas-solid reaction. Due to the enhancement of the close contact at interface, the ASSBs exhibit improved kinetic performance across a broad temperature range, especially at the freezing point. Besides, owing to the high-voltage tolerance of the protective layer, ASSBs demonstrate excellent cyclic stability under high cutoff voltages (500â cycles~94.0 % at 4.5â V, 200â cycles~80.4 % at 4.8â V). This work provides insights into using a high voltage stable oxyhalide coating strategy to enhance the development of high energy density ASSBs.
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Invasive fungal infections (IFIs) are common and life-threatening complications in post-hematopoietic stem cell transplantation (post-HSCT) recipients, Severe IFIs can lead to systemic infection and organ damage, which results in high mortality in HSCT recipients. With the development of the field of fungal infection diagnosis, more and more advanced non-culture diagnostic tools have been developed, such as glip biosensors, metagenomic next-generation sequencing, Magnetic Nanoparticles and Identified Using SERS via AgNPs+ , and artificial intelligence-assisted diagnosis. The advanced diagnostic approaches contribute to the success of HSCT and improve the overall survival of post-HSCT leukemia patients by supporting therapeutical decisions. This review provides an overview of the characteristics of two high-incidence IFIs in post-HSCT recipients and discusses some of the recently developed IFI detection technologies. Additionally, it explores the potential application of cationic conjugated polymer fluorescence resonance energy transfer (CCP-FRET) technology for IFI detection. The aim is to offer insights into selecting appropriate IFI detection methods and gaining an understanding of novel fungal diagnostic approaches in laboratory settings.
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Transplante de Células-Tronco Hematopoéticas , Infecções Fúngicas Invasivas , Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infecções Fúngicas Invasivas/diagnóstico , Transferência Ressonante de Energia de Fluorescência , Sequenciamento de Nucleotídeos em Larga Escala , Técnicas Biossensoriais/métodosRESUMO
All-solid-state batteries (ASSBs) represent a promising battery strategy to achieve high energy density with great safety. However, inadequate kinetic property and poor interfacial compatibility remain great challenges, which impede their practical application. A prototype of dual-ion conductor of Li+ synchronized with Cu+ unlocks a four-electron redox reaction with high reversibility and fast kinetics. As a result, the constructed ASSB exhibited a high reversible capacity of 603.0 mA·hour g-1 and an excellent cycling retention of 93.2% over 1500 cycles. Moreover, because of the ion highway connecting active materials and catholytes constructed by dual-ion conductor, remarkable temperature tolerance (-60°C) and excellent rate performance (231.6 mA·hour g-1 at 20 mA cm-2) were achieved. The superior electrochemical performance can be ascribed to the migration pathway with small energy barrier and low tortuosity once the Cu+ introduced into Li6PS5Cl. This work creates a unique perspective of ASSBs with dual-ion conducting strategy, thus inspiring a potential developing strategy of state-of-the-art ASSBs.
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Dasatinib is effective in the treatment of chronic and acute myeloid leukemia, which could cause the side effect of gastrointestinal bleeding by overdose or longtime use. Ruscogenin (RUS) from the traditional Chinese medicine Ophiopogon japonicas could protect endothelial microvascular barrier function. In this study, the therapeutic effect and underlying mechanisms of RUS were investigated on intestinal barrier dysfunction induced by dasatinib. Male C57BL/6 J mice were given three doses of dasatinib (70, 140, 210 mg/kg, ig) and RUS (3, 10, 30 µg/kg, ip) to explore the effect of dasatinib on intestinal barrier and the intervention of RUS. It was proved that dasatinib could reduce intestinal blood flow, inhibit phosphorylation of EGFR family member v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 4 (ErbB4)/YES-associated protein (YAP) and activation of Rho-associated coiled coil-containing protein kinase (ROCK)/phosphorylation of (myosin light chain) MLC. RUS could significantly increase intestinal blood flow, improve intestinal injury, reduce Evans blue leakage and serum content of FITC-dextran 4 kDa, and increase the expression of connexin (ZO-1, Occludin and VE-cadherin). Meanwhile, the in vitro effect of RUS (0.01, 0.1, 1 µM) on the dysfunction of the endothelial barrier was observed in dasatinib (150 nM)-pretreated HUVECs. The results showed that RUS suppressed dasatinib-induced the leakage of Evans blue, and degradation of F-actin and connexin. Furthermore, RUS could significantly increase the phosphorylation of ErbB4 at Tyr1284 site and YAP at Ser397 site, and inhibit ROCK expression and phosphorylation of MLC at Ser19 site in vivo and in vitro. In conclusion, the present research proved that RUS could suppress the side effects of dasatinib-induced intestinal barrier dysfunction by regulating ErbB4/YAP and ROCK/MLC pathways.
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Quinases Associadas a rho , Masculino , Camundongos , Animais , Dasatinibe/farmacologia , Azul Evans , Camundongos Endogâmicos C57BL , Fosforilação , Quinases Associadas a rho/metabolismoRESUMO
The enhancer of zeste homolog 2 (EZH2) is encoded by the Enhancer of zeste 2 polycomb repressive complex 2 subunit gene. EZH2 is involved in the cell cycle, DNA damage repair, cell differentiation, autophagy, apoptosis, and immunological modulation. The main function of EZH2 is to catalyze the methylation of H3 histone of H3K27Me3, which inhibits the transcription of target genes, such as tumor suppressor genes. EZH2 also forms complexes with transcriptions factors or directly binds to the promoters of target genes, leading to regulate gene transcriptions. EZH2 has been as a prominent target for cancer therapy and a growing number of potential targeting medicines have been developed. This review summarized the mechanisms that EZH2 regulates gene transcription and the interactions between EZH2 and important intracellular signaling molecules (Wnt, Notch, MEK, Akt) and as well the clinical applications of EZH2-targeted drugs.
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Proteína Potenciadora do Homólogo 2 de Zeste , Neoplasias , Humanos , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Complexo Repressor Polycomb 2/genética , Complexo Repressor Polycomb 2/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/genética , Histonas/metabolismo , MetilaçãoRESUMO
Primary myelofibrosis (PMF) is characterized by immature megakaryocytic hyperplasia, splenomegaly, extramedullary hematopoiesis and bone marrow fibrosis. Our preclinical study had demonstrated that aurora kinase A (AURKA) inhibitor MLN8237 reduced the mutation burden of PMF by inducing differentiation of immature megakaryocytes. However, it only slightly alleviated splenomegaly, reduced tissue fibrosis, and normalized megakaryocytes in PMF patients of the preliminary clinical study. So enhancing therapeutic efficacy of PMF is needed. In this study, we found that AURKA directly interacted with heat shock protein 90 (HSP90) and HSP90 inhibitors promoted the ubiquitin-dependent AURKA degradation. We demonstrated that HSP90 inhibitors 17-allylamino-17-demethoxygeldanamycin (17-AAG) and 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), normalized peripheral blood counts, improved splenomegaly, attenuated extramedullary hematopoiesis, decreased tissue fibrosis and reduced mutant burden in a MPLW515L mouse model of PMF. Importantly, both 17-AAG and 17-DMAG treatment at effective doses in vivo did not influence on hematopoiesis in healthy mice. Collectively, the study demonstrates that HSP90 inhibitors induce cell differentiation via the ubiquitin-dependent AURKA and also are safe and effective for the treatment of a MPLW515L mouse model of PMF, which may provide a new strategy for PMF therapy. Further, we demonstrate that combined therapy shows superior activity in acute megakaryocytic leukemia mouse model than single therapy.
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Antineoplásicos , Mielofibrose Primária , Camundongos , Humanos , Animais , Mielofibrose Primária/tratamento farmacológico , Mielofibrose Primária/genética , Aurora Quinase A , Esplenomegalia/tratamento farmacológico , Ubiquitina/farmacologia , Ubiquitina/uso terapêutico , Diferenciação Celular/genética , Antineoplásicos/uso terapêutico , Fibrose , Proteínas de Choque Térmico/farmacologia , Proteínas de Choque Térmico/uso terapêuticoRESUMO
BACKGROUND: Ruscogenin (RUS) has anti-inflammatory and antithrombotic effects, while its potential effects on deep venous thrombosis (DVT) and pulmonary embolism (PE) remain unclear. OBJECTIVE: We aimed to elucidate the effects of RUS on DVT and PE induced by the inferior vena cava stenosis (IVCS) model and investigate the underlying mechanism. METHODS: Male C57/BL6 mice were used to explore whether IVCS model could be complicated with deep venous thrombosis and pulmonary embolism. Then, effects of RUS on DVT and PE related inflammatory factors and coagulation were examined using H&E staining, ELISA, and real-time PCR. Western blot analysis was used to examine the effects of RUS on MEK/ERK/Egr-1/TF signaling pathway in PE. RESULTS: IVCS model induced DVT and complied with PE 48 h after surgery. Administration of RUS (0.01, 0.1, 1 mg/kg) inhibited DVT, decreased biomarker D-Dimer, cardiac troponin I, N-Terminal probrain natriuretic peptide in plasma to ameliorate PE induced by IVCS model. Meanwhile, RUS reduced tissue factor and fibrinogen content of lung tissue, inhibited P-selectin and C-reactive protein activity in plasma, and suppressed the expressions of interleukin-6 and interleukin-1ß in mice. Furthermore, RUS suppressed the phosphorylation of ERK1/2 and MEK1/2, decreasing the expressions of Egr-1 and TF in the lung. CONCLUSION: IVCS model contributed to the development of DVT and PE in mice and was associated with increased inflammation. RUS showed therapeutic effects by inhibiting inflammation as well as suppressing the activation of MEK/ERK/Egr-1/TF signaling pathway.
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Embolia Pulmonar , Trombose Venosa , Animais , Constrição Patológica/complicações , Inflamação/complicações , Sistema de Sinalização das MAP Quinases , Masculino , Camundongos , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Quinases de Proteína Quinase Ativadas por Mitógeno/farmacologia , Quinases de Proteína Quinase Ativadas por Mitógeno/uso terapêutico , Embolia Pulmonar/tratamento farmacológico , Transdução de Sinais , Espirostanos , Tromboplastina/metabolismo , Tromboplastina/farmacologia , Tromboplastina/uso terapêutico , Veia Cava Inferior/metabolismo , Trombose Venosa/tratamento farmacológicoRESUMO
The San Andreas Fault (SAF) showcases the breadth of possible earthquake sizes and occurrence behavior; in particular, the central SAF is a microcosm of such diversity. This section also exhibits the spectrum of fault coupling from locked to creeping. Here, we show that the observations of aseismic slip, temporal clustering of seismicity, and spatial variations in earthquake size distributions are tightly connected. Specifically, the creep rate along the central SAF is shown to be directly proportional to the fraction of nonclustered earthquakes for the period 1984-2020. This relationship provides a unified perspective of earthquake phenomenology along the SAF, where lower coupling manifests in weaker temporal clustering, with repeating earthquakes as an end-member. This new paradigm provides additional justification for characterizing the northwest â¼75 kilometers of the creeping segment as a transition zone, with potential implications for seismic hazard.
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Dasatinib, as a second-generation broad-spectrum tyrosine kinase inhibitor, presents an antitumor effect by inhibiting tyrosine kinases. However, dasatinib causes serious side effects, such as gastrointestinal bleeding and liver toxicity, possibly through the activation of ROCK kinase and MLC phosphorylation. At present, there is no effective prevention and treatment method. Previous research studies have shown that YQFM (YiQiFuMai powder injection) protects the blood-brain barrier by inhibiting the ROCK/MLC signaling pathway; whether YQFM can alleviate the side effects of dasatinib is unknown. In this study, dasatinib was injected (i.p. 70 mg/kg) and YQFM (i.p. 0.336 g/kg, 0.672 g/kg, 1.342 g/kg) was given in advance for 3 days to mice, to explore the effect of YQFM on side effects induced by Dasatinib. The results confirmed that YQFM significantly decreased Evans blue leakage in the small intestine and increased intestinal blood flow, increased the expression of ZO-1, Occludin, and VE-cadherin, and reduced the contents of D-lactic acid, s-VE-cadherin, Alanine aminotransferase (ALT), and Aspartate aminotransferase (AST) in serum. Finally, YQFM inhibited the expression of ROCK-1 and phosphorylation of MLC induced by Dasatinib. These findings suggested that YQFM could improve the side effects caused by Dasatinib linked with the ROCK/MLC signaling pathway, as shown in the graphical abstract.
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OBJECTIVE: Bulb suction drains have long been used in various surgical procedures. The purpose of this study was to evaluate 4 commonly used bulb suction devices in vitro to explore the nonlinear changes in draining ability and efficiency along with the conformation changes of the device throughout the draining processes. METHODS: Under a designed simulated scenario using pure water as the desired draining substance, the relative function of the J-VAC 100 cc (JV100) (Ethicon, Inc, Somerville, USA); the EVACUATOR 125cc (EP125) (Pacific Hospital Supply, Taiwan); the Bulb Reservoir 150 cc (BH150) (Hosmed, Inc, Miami, FL); and the HemoVac 400 cc (HV400) (Zimmer, Inc, Warsaw, IN) drains were compared. The maximum collection capacities and the dead space at maximum compression of each bulb drain were recorded and compared. The collected fluid weight was recorded along with time, and collection speeds were calculated and compared. RESULTS: The maximum collected weight of the 4 drains were 110.07 ± 0.54 g (JV100), 122.7 ± 06.51 g (EP125), 140.8 ± 03.78 g (BH150), and 335.07 ± 04.24 g (HV400). The dead spaces under maximum compression were 15.63 ± 01.32 ml, 19.80 ± 03.37 ml, 34.23 ± 06.77 ml, and 82.83 ± 05.51 ml, respectively. The collecting speed-volume curves were generated from the authors' tested devices. Although slightly different individually, typical characteristics, such as tendency to reach maximum collection speed at the very beginning of the collection phase; rapid decline to about 65% of peak collection speed when approximately 30% of the total collection volume had been achieved; and inefficient collection speed in the later collection phase were noted. CONCLUSIONS: Among all the bulb drains tested in this study, all of them performed well in vitro. Although using bulb drains continues to be an effective and economic draining method after operation, clinicians should be aware of the nonlinear features of suction efficiency during the drainage process to avoid unexpected function deterioration. .
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Fossa Craniana Média/patologia , Neoplasias da Base do Crânio/diagnóstico , Sinovite Pigmentada Vilonodular/diagnóstico , Transtornos da Articulação Temporomandibular/diagnóstico , Craniotomia , Diagnóstico Diferencial , Orelha Média/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética/métodos , Processo Mastoide/diagnóstico por imagem , Pessoa de Meia-Idade , Radioterapia Adjuvante , Neoplasias da Base do Crânio/patologia , Osso Temporal/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodosRESUMO
Spinal epidural lipomatosis (SEL), an abnormal localized or tumor-like accumulation of fat in the epidural space, is an infrequent complication of chronic steroid usage and an uncommon cause of spinal cord compression. During the period of 1990 to 2006, we have two cases of medically heath SEL patients without history of steroid administration. Their initial clinical manifestations were low back pain, progressive lower extremities weakness, numbness, followed by rapid deterioration of neurogenic intermittent claudication. They were misdiagnosed and treated as degenerative spinal disease for a long time. Due to prominent neurological deficit, lumbar magnetic resonance image (MRI) was obtained and showed SEL. These 2 patients all underwent laminectomy and removal of epidural fat. Postoperatively, they both showed improvement. We reviewed the literature and discussed the current concept in the management of SEL.
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Espaço Epidural/patologia , Lipomatose/patologia , Doenças da Medula Espinal/patologia , Adulto , Humanos , Lipomatose/etiologia , Lipomatose/cirurgia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Doenças da Medula Espinal/etiologia , Doenças da Medula Espinal/cirurgiaRESUMO
Intracranial arachnoid cysts are believed to be congenital; they can become symptomatic in pediatric patients. Chronic subdural hematomas tend to occur in elderly patients with a history of mild head injury a few months prior to the onset of symptoms. However, these two distinct clinical entities sporadically occur together in relatively young patients. We report a 29-year-old man who presented with headache and dizziness of 2 months' duration. Brain computed tomography revealed a huge chronic subdural hematoma over the left frontoparietal lobe, with an incidental finding of an arachnoid cyst over the left sylvian fissure. In light of a literature review, we discuss arachnoid cysts as a possible risk factor for subdural hematoma, especially in young adults.