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The continuous solid-electrolyte interphase (SEI) accumulation has been blamed for the rapid capacity loss of carbon anodes in Na and K ethylene carbonate (EC)/diethyl carbonate (DEC) electrolytes, but the understanding of the SEI composition and its formation chemistry remains incomplete. Here, we explain this SEI accumulation as the continuous production of organic species in solution-phase reactions. By comparing the NMR spectra of SEIs and model compounds we synthesized, alkali metal ethyl carbonate (MEC, M = Na or K), long-chain alkali metal ethylene carbonate (LCMEC, M = Na or K), and poly(ethylene oxide) (PEO) oligomers with ethyl carbonate ending groups are identified in Na and K SEIs. These components can be continuously generated in a series of solution-phase nucleophilic reactions triggered by ethoxides. Compared with the Li SEI formation chemistry, the enhancement of the nucleophilicity of an intermediate should be the cause of continuous nucleophilic reactions in the Na and K cases.
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The realization and discovery of quantum spin liquid (QSL) candidate materials are crucial for exploring exotic quantum phenomena and applications associated with QSLs. Most existing metal-organic two-dimensional (2D) quantum spin liquid candidates have structures with spins arranged on the triangular or kagome lattices, whereas honeycomb-structured metal-organic compounds with QSL characteristics are rare. Here, we report the use of 2,5-dihydroxy-1,4-benzoquinone (X2dhbq, X = Cl, Br, H) as the linkers to construct cobalt(II) honeycomb lattices (NEt4)2[Co2(X2dhbq)3] as promising Kitaev-type QSL candidate materials. The high-spin d7 Co2+ has pseudospin-1/2 ground-state doublets, and benzoquinone-based linkers not only provide two separate superexchange pathways that create bond-dependent frustrated interactions but also allow for chemical tunability to mediate magnetic coupling. Our magnetization data show antiferromagnetic interactions between neighboring metal centers with Weiss constants from -5.1 to -8.5 K depending on the X functional group in X2dhbq linkers (X = Cl, Br, H). No magnetic transition or spin freezing could be observed down to 2 K. Low-temperature susceptibility (down to 0.3 K) and specific heat (down to 0.055 K) of (NEt4)2[Co2(H2dhbq)3] were further analyzed. Heat capacity measurements confirmed no long-range order down to 0.055 K, evidenced by the broad peak instead of the λ-like anomaly. Our results indicate that these 2D cobalt benzoquinone frameworks are promising Kitaev QSL candidates with chemical tunability through ligands that can vary the magnetic coupling and frustration.
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Limited electrochemical stability windows of conventional carbonate-based electrolytes pose a challenge to support the Lithium (Li)- and manganese (Mn)-rich (LMR) high-voltage cathodes in rechargeable Li-metal batteries (LMBs). To address this issue, a novel localized high-concentration electrolyte (LHCE) composition incorporating LiPF6 and LiTFSI as dual-salts (D-LHCE), tailored for high-voltage (>4.6 Vvs.Li) operation of LMR cathodes in LMBs is introduced. 7Li nuclear magnetic resonance and Raman spectroscopy revealed the characteristics of the solvation structure of D-LHCE. The addition of LiPF6 provides stable Al-current-collector passivation while the addition of LiTFSI improves the stability of D-LHCE by producing a more robust cathode-electrolyte interphase (CEI) on LMR cathode and solid-electrolyte interphase (SEI) on Li-metal anode. As a result, LMR/Li cell, using the D-LHCE, achieved 72.5% capacity retention after 300 cycles, a significant improvement compared to the conventional electrolyte (21.9% after 100 cycles). The stabilities of LMR CEI and Li-metal SEI are systematically analyzed through combined applications of electrochemical impedance spectroscopy and distribution of relaxation times techniques. The results present that D-LHCE concept represents an effective strategy for designing next-generation electrolytes for high-energy and high-voltage LMB cells.
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Solid-state sodium metal batteries have been extensively investigated because of their potential to improve safety, cost-effectiveness, and energy density. The development of such batteries urgently required a solid-state electrolyte with fast Na-ion conduction and favorable interfacial compatibility. Herein, the progress on developing the NaB3H8 solid-state electrolytes is reported, which show a liquid-like ionic conductivity of 0.05 S cm-1 at 56 °C with an activation energy of 0.35 eV after an order-disorder phase transformation, matching or surpassing the best single-anion hydridoborate conductors investigated up to now. The steady polarization voltage and significantly decreased resistance are achieved in the symmetric Na/NaB3H8/Na cell, indicating the great electrochemical stability and favorable interfacial contact with the Na metal of NaB3H8. Furthermore, a Na/NaB3H8/TiS2 battery, the first high-rate (up to 1 C) solid-state sodium metal battery using the single-anion hydridoborate electrolyte, is demonstrated, which exhibits superior rate capability (168.2 mAh g-1 at 0.1 C and 141.2 mAh g-1 at 1 C) and long-term cycling stability (70.9% capacity retention at 1 C after 300 cycles) at 30 °C. This work may present a new possibility to solve the interfacial limitations and find a new group of solid-state electrolytes for high-performance sodium metal batteries.
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A deep understanding of the oxygen (O2) reduction and evolution mechanisms is crucial for understanding metal-O2 batteries. It has become evident that the instability of superoxide in the presence of lithium (Li) ions and sodium (Na) ions is the root cause for the poor reversibility and energy efficiency of Li-O2 and Na-O2 batteries. A straightforward yet elegant method is stabilizing superoxide with the larger potassium (K) ions. Superoxide-based K-O2 batteries, invented by our group in 2013, are operated based on one-electron redox of O2/potassium superoxide (KO2) and have high energy efficiencies without any electrocatalysts. Nevertheless, limiting the anionic redox to O2/superoxide affects the capacity output. Therefore, it is attractive to explore the possibility of beyond KO2 in the K-O2 batteries, especially if the use of catalysts can still be avoided. In this research, solid KO2 was used as the condensed O2 source and pre-dissolved in the dimethyl sulfoxide (DMSO)-based electrolyte. It is encouraging to observe two sets of reversible peaks during the three-electrode cyclic voltammetry scan under an argon atmosphere. One pair of peaks is attributed to the KO2/potassium peroxide (K2O2) interconversion. Such redox has superb reversibility and a small overpotential of 239 mV in the absence of explicit electrocatalysts. Notably, it is further revealed that K2O2 reacts with gaseous O2. Therefore, a gas-open system with an O2 supply is unfavorable for realizing the reversible KO2/K2O2 redox, and a closed cell system with a KO2 supply as the starting active material is suggested instead.
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Chiral organic-inorganic metal halides (OIMHs) are attractive for their potential applications in chiral optoelectronics and spintronics, such as circular polarized light emitters, detectors, and chiral-induced spin selectivity. Here, we report three pairs of chiral OIMHs with great water stability constructed from chiral viologens. These OIMHs contain either 1D or 0D structures, however, with small band gaps around 2 eV. Circular dichroism (CD) spectroscopy on transparent thin films of two OIMH pairs showed a wide CD response covering most of the visible light range. Although the chiral center is not directly attached to the pyridinium in these chiral viologens, the chirality is still successfully transferred into both the band gap and the exciton absorption ranges. Liquid and solid CD studies of the chiral viologens further indicate that the chiral induction inside these OIMHs is possibly through chiral crystallization. This work demonstrated the design strategy of water-stable, small band gap chiral OIMHs through chiral viologens. These low-dimensional chiral materials may provide an interesting system to investigate chiral induction, and their broad CD response may enable their potential application as circular photodetectors with a wide detection range.
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BACKGROUND: Chronic lymphocytic leukaemia (CLL) is the most common lymphoproliferative disease in adults and currently remains incurable. As the progression-free period shortens after each successive treatment, strategies such as maintenance therapy are needed to improve the degree and duration of response to previous therapies. Monoclonal antibodies, immunomodulatory agents, and targeted therapies are among the available options for maintenance therapy. People with CLL who achieve remission after previous therapy may choose to undergo medical observation or maintenance therapy to deepen the response. Even though there is widespread use of therapeutic maintenance agents, the benefits and harms of these treatments are still uncertain. OBJECTIVES: To assess the effects and safety of maintenance therapy, including anti-CD20 monoclonal antibody, immunomodulatory drug therapy, anti-CD52 monoclonal antibody, Bruton tyrosine kinase inhibitor, and B-cell lymphoma-2 tyrosine kinase inhibitor, for individuals with CLL. SEARCH METHODS: We conducted a comprehensive literature search for randomised controlled trials (RCTs) with no language or publication status restrictions. We searched CENTRAL, MEDLINE, Embase, and three trials registers in January 2022 together with reference checking, citation searching, and contact with study authors to identify additional studies. SELECTION CRITERIA: We included RCTs with prospective identification of participants. We excluded cluster-randomised trials, cross-over trial designs, and non-randomised studies. We included studies comparing maintenance therapies with placebo/observation or head-to-head comparisons. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. We assessed risk of bias in the included studies using Cochrane's RoB 1 tool for RCTs. We rated the certainty of evidence for the following outcomes using the GRADE approach: overall survival (OS), health-related quality of life (HRQoL), grade 3 and 4 adverse events (AEs), progression-free survival (PFS), treatment-related mortality (TRM), treatment discontinuation (TD), and all adverse events (AEs). MAIN RESULTS: We identified 11 RCTs (2393 participants) that met the inclusion criteria, including seven trials comparing anti-CD20 monoclonal antibodies (mAbs) (rituximab or ofatumumab) with observation in 1679 participants; three trials comparing immunomodulatory drug (lenalidomide) with placebo/observation in 693 participants; and one trial comparing anti-CD 52 mAbs (alemtuzumab) with observation in 21 participants. No comparisons of novel small molecular inhibitors were found. The median age of participants was 54.1 to 71.7 years; 59.5% were males. The type of previous induction treatment, severity of disease, and baseline stage varied among the studies. Five trials included early-stage symptomatic patients, and three trials included advanced-stage patients (Rai stage III/IV or Binet stage B/C). Six trials reported a frequent occurrence of cytogenic aberrations at baseline (69.7% to 80.1%). The median follow-up duration was 12.4 to 73 months. The risk of selection bias in the included studies was unclear. We assessed overall risk of performance bias and detection bias as low risk for objective outcomes and high risk for subjective outcomes. Overall risk of attrition bias, reporting bias, and other bias was low. Anti-CD20 monoclonal antibodies (mAbs): rituximab or ofatumumab maintenance versus observation Anti-CD20 mAbs maintenance likely results in little to no difference in OS (hazard ratio (HR) 0.94, 95% confidence interval (CI) 0.73 to 1.20; 1152 participants; 3 studies; moderate-certainty evidence) and likely increases PFS significantly (HR 0.61, 95% CI 0.50 to 0.73; 1255 participants; 5 studies; moderate-certainty evidence) compared to observation alone. Anti-CD20 mAbs may result in: an increase in grade 3/4 AEs (rate ratio 1.34, 95% CI 1.06 to 1.71; 1284 participants; 5 studies; low-certainty evidence); little to no difference in TRM (risk ratio 0.82, 95% CI 0.39 to 1.71; 1189 participants; 4 studies; low-certainty evidence); a slight reduction to no difference in TD (risk ratio 0.93, 95% CI 0.72 to 1.20; 1321 participants; 6 studies; low-certainty evidence); and an increase in all AEs (rate ratio 1.23, 95% CI 1.03 to 1.47; 1321 participants; 6 studies; low-certainty evidence) compared to the observation group. One RCT reported that there may be no difference in HRQoL between the anti-CD20 mAbs (ofatumumab) maintenance and the observation group (mean difference -1.70, 95% CI -8.59 to 5.19; 480 participants; 1 study; low-certainty evidence). Immunomodulatory drug (IMiD): lenalidomide maintenance versus placebo/observation IMiD maintenance therapy likely results in little to no difference in OS (HR 0.91, 95% CI 0.61 to 1.35; 461 participants; 3 studies; moderate-certainty evidence) and likely results in a large increase in PFS (HR 0.37, 95% CI 0.19 to 0.73; 461 participants; 3 studies; moderate-certainty evidence) compared to placebo/observation. Regarding harms, IMiD maintenance therapy may result in an increase in grade 3/4 AEs (rate ratio 1.82, 95% CI 1.38 to 2.38; 400 participants; 2 studies; low-certainty evidence) and may result in a slight increase in TRM (risk ratio 1.22, 95% CI 0.35 to 4.29; 458 participants; 3 studies; low-certainty evidence) compared to placebo/observation. The evidence for the effect on TD compared to placebo is very uncertain (risk ratio 0.71, 95% CI 0.47 to 1.05; 400 participants; 2 studies; very low-certainty evidence). IMiD maintenance therapy probably increases all AEs slightly (rate ratio 1.41, 95% CI 1.28 to 1.54; 458 participants; 3 studies; moderate-certainty evidence) compared to placebo/observation. No studies assessed HRQoL. Anti-CD52 monoclonal antibodies (mAbs): alemtuzumab maintenance versus observation Maintenance with alemtuzumab may have little to no effect on PFS, but the evidence is very uncertain (HR 0.55, 95% CI 0.32 to 0.95; 21 participants; 1 study; very low-certainty evidence). We did not identify any study reporting the outcomes OS, HRQoL, grade 3/4 AEs, TRM, TD, or all AEs. AUTHORS' CONCLUSIONS: There is currently moderate- to very low-certainty evidence available regarding the benefits and harms of maintenance therapy in people with CLL. Anti-CD20 mAbs maintenance improved PFS, but also increased grade 3/4 AEs and all AEs. IMiD maintenance had a large effect on PFS, but also increased grade 3/4 AEs. However, none of the above-mentioned maintenance interventions show differences in OS between the maintenance and control groups. The effects of alemtuzumab maintenance are uncertain, coupled with a warning for drug-related infectious toxicity. We found no studies evaluating other novel maintenance interventions, such as B-cell receptor inhibitors, B-cell leukaemia-2/lymphoma-2 inhibitors, or obinutuzumab.
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Antineoplásicos , Leucemia Linfocítica Crônica de Células B , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Alemtuzumab , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/efeitos adversos , Lenalidomida/uso terapêutico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Rituximab/efeitos adversosRESUMO
High sperm cryotolerance is crucial to the successful cryopreservation of boar sperm. Evaluating the cryotolerance of boar sperm by using a rapid and convenient technique can enhance the commercial viability of these sperm. This study investigated the correlation between sperm parameters for three sample subsets-fresh sperm, sperm with H2O2-induced oxidative damage (hereinafter referred to as H2O2-induced sperm), and frozen-thawed sperm-to identify the potential of these correlations to predict cryotolerance. A total of 64 sperm samples were obtained from 64 Duroc boars. The sperm parameters of the three subsets, where the frozen-thawed sperm were analysed at 30 or 180 min after thawing, were determined, and the coefficients of correlation between these parameters were calculated. The results indicated that H2O2-induced oxidative stress resulted in decreases in various sperm parameters-including total motility (TM), viability (VIA), mitochondrial membrane potential (MMP), and live sperm with MMP (LMP)-but increased their coefficients of variation. Receiver operating characteristic (ROC) curve analysis revealed that the kinematic parameters of the H2O2-induced sperm effectively predicted those of the frozen-thawed boar sperm at 30 min after thawing; the corresponding area under the ROC curve (AUC) was 0.8667 for TM and 0.8733 for progressive motility in the H2O2-induced sperm. For measurement at 180 min after thawing, the sperm membrane and mitochondrial parameters of the H2O2-induced sperm effectively predicted the LMP of the frozen-thawed boar sperm; the corresponding AUC was 0.8489 for VIA, 0.8289 for MMP, and 0.8444 for LMP. To our knowledge, this is the first study to directly establish a strong correlation between post-thaw boar sperm quality and H2O2-induced oxidative stress before freezing. Our proposed technique can serve as a valuable reference for the development of practical applications aimed at enhancing techniques for cryopreserving boar sperm.
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Antioxidantes , Preservação do Sêmen , Suínos , Masculino , Animais , Antioxidantes/farmacologia , Sêmen , Peróxido de Hidrogênio/farmacologia , Preservação do Sêmen/veterinária , Preservação do Sêmen/métodos , Espermatozoides , Criopreservação/veterinária , Criopreservação/métodos , Motilidade dos EspermatozoidesRESUMO
All-solid-state sodium metal batteries are promising for large-scale energy storage applications owing to their intrinsic safety and cost-effectiveness. However, they generally suffer from sodium dendrite growth or rapid capacity fading, especially at high rates, mainly due to poor wettability, sluggish ionic transport, or low interfacial stability of the solid electrolytes. Herein, we report a novel composite, NaB3H8 â xNH3@NaB3H8 (x<1), as a new class of solid electrolyte for high-rate batteries. NaB3H8 â xNH3@NaB3H8 is obtained from the sticky NaB3H8 â NH3 after removal of NH3 partially at room temperature. It delivers an ionic conductivity of 0.84â mS cm-1 at 25 °C and reaches 20.64â mS cm-1 at 45 °C after an order-disorder phase transformation. It also reveals a good capability of dendrite suppression and remarkable stability against sodium metal. These performances enable the all-solid-state Na//TiS2 battery with a high capacity of 232.4â mAh g-1 (97.2 % of theoretical capacity) and long-term cycling stability at 1â C. Notably, this battery shows superior long-life cycling stability even at 5 and 10â C, which has been rarely reported in all-solid-state sodium metal batteries. This work opens a new group of solid electrolytes, contributing to fast-charging or high-power-density sodium metal batteries.
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In this work we have determined that heat shock protein 90 (Hsp90) is essential for avian reovirus (ARV) replication by chaperoning the ARV p17 protein. p17 modulates the formation of the Hsp90/Cdc37 complex by phosphorylation of Cdc37, and this chaperone machinery protects p17 from ubiquitin-proteasome degradation. Inhibition of the Hsp90/Cdc37 complex by inhibitors (17-N-allylamino-17-demethoxygeldanamycin 17-AGG, and celastrol) or short hairpin RNAs (shRNAs) significantly reduced expression levels of viral proteins and virus yield, suggesting that the Hsp90/Cdc37 chaperone complex functions in virus replication. The expression levels of p17 were decreased at the examined time points (2 to 7 h and 7 to 16 h) in 17-AAG-treated cells in a dose-dependent manner while the expression levels of viral proteins σA, σC, and σNS were decreased at the examined time point (7 to 16 h). Interestingly, the expression levels of σC, σA, and σNS proteins increased along with coexpression of p17 protein. p17 together with the Hsp90/Cdc37 complex does not increase viral genome replication but enhances viral protein stability, maturation, and virus production. Virus factories of ARV are composed of nonstructural proteins σNS and µNS. We found that the Hsp90/Cdc37 chaperone complex plays an important role in accumulation of the outer-capsid protein σC, inner core protein σA, and nonstructural protein σNS of ARV in viral factories. Depletion of Hsp90 inhibited σA, σC, and p17 proteins colocalized with σNS in viral factories. This study provides novel insights into p17-modulated formation of the Hsp90/Cdc37 chaperone complex governing virus replication via stabilization and maturation of viral proteins and accumulation of viral proteins in viral factories for virus assembly. IMPORTANCE Molecular mechanisms that control stabilization of ARV proteins and the intermolecular interactions among inclusion components remain largely unknown. Here, we show that the ARV p17 is an Hsp90 client protein. The Hsp90/Cdc37 chaperone complex is essential for ARV replication by protecting p17 chaperone from ubiquitin-proteasome degradation. p17 modulates the formation of Hsp90/Cdc37 complex by phosphorylation of Cdc37, and this chaperone machinery protects p17 from ubiquitin-proteasome degradation, suggesting a feedback loop between p17 and the Hsp90/Cdc37 chaperone complex. p17 together with the Hsp90/Cdc37 complex does not increase viral genome replication but enhances viral protein stability and virus production. Depletion of Hsp90 prevented viral proteins σA, σC, and p17 from colocalizing with σNS in viral factories. Our findings elucidate that the Hsp90/Cdc37 complex chaperones p17, which, in turn, promotes the synthesis of viral proteins σA, σC, and σNS and facilitates accumulation of the outer-capsid protein σC and inner core protein σA in viral factories for virus assembly.
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Proteínas de Ciclo Celular , Chaperoninas , Proteínas de Choque Térmico HSP90 , Orthoreovirus Aviário , Proteínas Virais , Replicação Viral , Animais , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/metabolismo , Proteínas de Ciclo Celular/metabolismo , Chaperoninas/metabolismo , Genoma Viral , Proteínas de Choque Térmico HSP90/genética , Proteínas de Choque Térmico HSP90/metabolismo , Orthoreovirus Aviário/fisiologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Ubiquitina/metabolismo , Proteínas do Envelope Viral/metabolismo , Proteínas Virais/genética , Proteínas Virais/metabolismo , Replicação Viral/genéticaRESUMO
BACKGROUND: Lung cancer has the highest mortality rate in the world, and mounting evidence suggests that cancer stem cells (CSCs) are associated with poor prognosis, recurrence, and metastasis of lung cancer. It is urgent to identify new biomarkers and therapeutic targets for targeting lung CSCs. METHODS: We computed the single-sample gene set enrichment analysis (ssGSEA) of 1554 Reactome gene sets to identify the mRNA expression-based stemness index (mRNAsi)-associated pathways using the genome-wide RNA sequencing data of 509 patients from The Cancer Genome Atlas (TCGA) cohort of lung adenocarcinoma (LUAD). Phenotypic effects of ubiquitin-specific peptidase 5 (USP5) on the CSC-like properties and metastasis were examined by in vitro sphere formation assay, migration assay, invasion assay, and in vivo xenografted animal models. Cycloheximide chase assay, co-immunoprecipitation assay, and deubiquitination assay were performed to confirm the effect of USP5 on the deubiquitination of ß-catenin. RESULTS: We demonstrated that USP5 expression were positively correlated with the stemness-associated signatures and poor outcomes in lung cancer specimens. Silencing of endogenous USP5 reduced CSC-like characteristics, epithelial-mesenchymal transition (EMT), and metastasis in vitro and in vivo. Furthermore, USP5 interacted with ß-catenin, which resulted in deubiquitination, stabilization of ß-catenin, and activation of Wnt/ß-catenin pathway. Accordingly, expression of USP5 was positively correlated with the enrichment score of the Wnt/TCF pathway signature in human lung cancer. Silencing of ß-catenin expression suppressed USP5-enhancing sphere formation. Targeting USP5 with the small molecule WP1130 promoted the degradation of ß-catenin, and showed great inhibitory effects on sphere formation, migration, and invasion. Finally, we identified a poor-prognosis subset of tumors characterized by high levels of USP5, Wnt signaling score, and Stemness score in both TCGA-LUAD and Rousseaux_2013 datasets. CONCLUSIONS: These findings reveal a clinical evidence for USP5-enhanced Wnt/ß-catenin signaling in promoting lung cancer stemness and metastasis, implying that targeting USP5 could provide beneficial effects to improve lung cancer therapeutics.
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OBJECTIVES: Neuropsychiatric systemic lupus erythematosus (NPSLE) is associated with adverse outcomes; however, imaging abnormalities are only detectable by conventional brain magnetic resonance imaging (MRI) in up to 50% of patients. This study investigated the variability in cortical thickness and diffusion tensor imaging (DTI) parameters among patients with NPSLE whose brain morphology appeared normal on conventional MRI. METHODS: This retrospective study enrolled 27 female patients with NPSLE (median age: 41.0 years, range: 22-63 years) and 34 female healthy controls (median age: 37.0 years, range: 24-55 years). None exhibited evident abnormalities on conventional MRI. Regional volumes, cortical thickness, and DTI parameters, including fractional anisotropy (FA) and mean diffusivity (MD), were compared. Age-adjusted multivariable logistic regression analysis was conducted to detect significant NPSLE-associated differences. RESULTS: No significant differences in grey or white matter volume fractions were observed between the groups. However, the NPSLE group demonstrated significant cortical thinning in the right pars opercularis (2.45 vs 2.52 mm, p = 0.007), reduced FA values in the fornix (0.35 vs 0.40, p = 0.001) and left anterior limb of internal capsule (0.50 vs 0.52, p = 0.012), and increased MD in the fornix (1.71 vs 1.48, p = 0.009) and left posterior corona radiata (0.80 vs 0.76, p = 0.005) compared with those of healthy controls. CONCLUSIONS: Cortical thickness measurements and DTI analyses can be used to detect differential variations in patients with NPSLE who exhibit an otherwise normal brain structure on conventional MRI, indicating the existence of subtle changes despite the absence of obvious macrostructural central nervous system involvement of lupus.
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Lúpus Eritematoso Sistêmico , Vasculite Associada ao Lúpus do Sistema Nervoso Central , Humanos , Feminino , Adulto , Vasculite Associada ao Lúpus do Sistema Nervoso Central/patologia , Imagem de Tensor de Difusão/métodos , Lúpus Eritematoso Sistêmico/complicações , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Encéfalo/patologiaRESUMO
BACKGROUND: Hyperlipidemia is a major risk factor for vascular endothelial injury and atherosclerosis leading to cardiovascular diseases. Early diagnosis of vascular endothelial injury is important for the prevention and prognosis of cardiovascular diseases. This study aimed to investigate sensitive circulating microRNA (miRNA) as a potential diagnostic biomarker of vascular endothelial injury in a hyperlipidemic rat model. METHODS: The miRNA expression profile was detected by miRNA microarray. The hyperlipidemic rat model was established by intraperitoneal injection of vitamin D3 combined with a high-fat diet. Plasma miRNA levels were measured by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). RESULTS: No significant difference was found in the types of highly expressed miRNAs between human umbilical artery endothelial cells (HUAEC) and human umbilical vein endothelial cells (HUVEC). A total of 10 highly expressed miRNAs in endothelial cells were selected as candidate miRNAs, including miR-21, miR-126, let-7a, miR-23a, miR-221, miR-125b, miR-26a, miR-29a, miR-16, and miR-100. The plasma levels of let-7a, miR-126, miR-21, and miR-26a were significantly elevated in hyperlipidemic rats at 30 and 50 days after modeling, while the plasma level of miR-29a was significantly decreased. No significant change was found in the plasma levels of miR-125b, miR-23a, miR-221, miR-100, and miR-16. Interestingly, a significant reduction in plasma miR-29 level was detected as early as 20 days after modeling, which was earlier than for soluble intercellular adhesion molecule1 (sICAM-1). CONCLUSION: The plasma levels of endothelial cell-enriched miRNAs were correlated with vascular endothelial injury induced by hyperlipidemia. miR-29a might serve as a potential early diagnostic biomarker of endothelial injury-related diseases.
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Doenças Cardiovasculares , Hiperlipidemias , MicroRNAs , Humanos , Animais , Ratos , Células Endoteliais , MicroRNAs/genética , BiomarcadoresRESUMO
A battery cathode based on the superoxide/peroxide redox not only inherits the advantage of oxygen (O2 ) batteries in high capacities and low costs but also overcomes the disadvantages in O2 storage, electrolyte evaporation, and anode deactivation due to O2 crossover. Herein, we report an enhanced potassium superoxide (KO2 )/peroxide (K2 O2 ) conversion by adopting a high-donicity anion additive in the ether-based electrolyte. Such an anion was synthesized via a "Solvent-in-Anion" strategy and validated to enhance the electron donicity of the electrolyte. The use of high-donicity anion could lead to enhanced KO2 utilization (≈90.2 %) by retarding electrode passivation and allow the full charging back of K2 O2 through the solution-mediated pathway without electrocatalysts. No apparent cell degradation is observed during the first 120â cycles by controlling the reversible depth-of-discharge capacity at 292â mAh g-1 KO 2 ${{_{{\rm KO}{_{2}}}}}$ within an O2 -free region. The K-KO2 cell delivers a high energy efficiency (>84.4 %) and a lifespan of over 1440â hours.
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High intake of phytoestrogen has been reported to be associated with the prevention of colorectal cancer (CRC). Calycosin belongs to the phytoestrogen that has been shown to suppress CRC cells in our previous study. However, its anticancer activity and molecular mechanisms have not been elucidated. In this study, we analyzed the effect of calycosin on the viability and apoptosis of human CRC HCT116 and SW480 cells via MTT assay, flow cytometry assay, and caspase-3/7 activity assay. The protein expressions of estrogen receptor ß (ERß), PTEN, and PI3K/Akt signal pathways were determined by Western blot analysis. And then, the alterations of biological behavior in CRC cells transfected with ERß siRNA were analyzed. Mouse xenograft models were further performed to detect the antitumor effect in vivo. The results show that calycosin reduces CRC cell viability, induces cell apoptosis, and suppresses xenograft tumor growth. The protein expressions of ERß and PTEN are significantly upregulated following calycosin treatment, whereas p-AKT/AKT ratio and Bcl-2 level are downregulated. Suppressing ERß with siRNA partially attenuates the reduction in viability and apoptosis induced by calycosin. Our results indicate that calycosin shows inhibitory effects on CRC cells, which might be obtained by targeting ERß, upregulating PTEN, and inhibiting the PI3K/Akt signal pathway.
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Neoplasias Colorretais , Receptor beta de Estrogênio , Animais , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Colorretais/metabolismo , Receptor beta de Estrogênio/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Isoflavonas , Camundongos , PTEN Fosfo-Hidrolase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fitoestrógenos/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Interferente Pequeno/farmacologia , Transdução de SinaisRESUMO
Background and Objectives: Postoperative adjuvant therapy with uracil and tegafur (UFT) is often used for stage II colon cancer in Japan, but a limited number of studies have investigated the effects of UFT in these patients. Materials and Methods: We conducted a population-based cohort study in patients with resected stage II colon cancer comparing the outcomes after postoperative adjuvant chemotherapy with UFT with an observation-only group. The data were collected from the Taiwan National Health Insurance Research Database from 2000 to 2015. The outcomes of the study were disease-free survival (DFS) and overall survival (OS). The hazard ratios (HRs) were calculated using multivariate Cox proportional hazard regression models. Results: No differences in the DFS and OS were detected between the UFT (1137 patients) and observation (2779 patients) cohorts (DFS: adjusted HR 0.702; 95% confidence interval (CI) 0.489-1.024; p = 0.074) (OS: adjusted HR 0.894; 95% CI 0.542-1.186; p = 0.477). In the subgroup analyses of the different substages, UFT prolonged DFS in patients with stage IIA colon cancer (adjusted HR 0.652; 95% CI 0.352-0.951; p = 0.001) compared with DFS in the observation cohort, but no differences in the OS were detected (adjusted HR 0.734; 95% CI 0.475-1.093; p = 0.503). Conclusions: Our results show that DFS improved significantly in patients with stage IIA colon cancer receiving UFT as a postoperative adjuvant chemotherapy compared with DFS in the observation group.
Assuntos
Neoplasias do Colo , Tegafur , Humanos , Tegafur/uso terapêutico , Uracila/uso terapêutico , Estudos de Coortes , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estadiamento de Neoplasias , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/cirurgia , Quimioterapia Adjuvante , Intervalo Livre de DoençaRESUMO
Localized high-concentration electrolytes (LHCEs) have attracted interest in alkali metal batteries due to the advantages of forming stable solid-electrolyte interphases (SEIs) on anodes and good chemical/electrochemical stability. Herein, a new degradation mechanism is revealed for ether-based LHCEs that questions their compatibility with alkali metal anodes (Li, Na, and K). Specifically, the ether solvent reacts with alkali metals to generate solvated electrons (es - ) that attack hydrofluoroether co-solvents to form a series of byproducts. The ether solvent essentially acts as a phase-transfer reagent that continuously transfers electrons from solid-phase metals into the solution phase, thus inhibiting the formation of stable SEI and leading to continuous alkali metal corrosion. Switching to an ester-based solvating solvent or intercalation anodes such as graphite or molybdenum disulfide has been shown to avoid such a degradation mechanism due to the absence of es - .
RESUMO
Solid-state K-ion conducting electrolytes are key elements to address the current problems in K secondary batteries. Here, we report a sulfide-based K-ion conductor K3 SbS4 with a low-activation energy of 0.27â eV. W-doped K3-x Sb1-x Wx S4 (x=0.04, 0.06, 0.08, 0.10 and 0.12) compounds were also explored for increasing vacancy concentrations and improving ionic conductivity. Among them, K2.92 Sb0.92 W0.08 S4 exhibits the highest conductivity of 1.4×10-4 â S cm-1 at 40 °C, which is among the best reported potassium-ion conductors at ambient temperature. In addition, K2.92 Sb0.92 W0.08 S4 is electrochemically stable with long-chained potassium polysulfide of K2 Sx . A room-temperature solid potassium-sulfur (K-S) battery system has therefore been successfully demonstrated, which is the first K-S battery prototype using non-commercial inorganic-based electrolyte to block the polysulfide shuttle.
RESUMO
A new Rh2(II,II) dimer has been synthesized and anchored onto a NiO photocathode. The dirhodium complex acts as both the sensitizer to inject holes into NiO and as catalyst for the production of hydrogen. The single-molecule design circumvents limitations of the conventional multicomponent approach with separate sensitizer and catalyst, thus simplifying the hydrogen production pathway and reducing energy losses associated with additional intermolecular charge transfer steps. The Rh2(II,II) complex absorbs strongly from the ultraviolet throughout the visible range and tails into the near-IR to â¼800 nm, permitting absorption of a significantly greater portion of the solar irradiance as compared to traditional dyes used in dye-sensitized solar cells and photoelectrosynthesis cells. The irradiation of the Rh2-NiO photoelectrode with 655 nm light (53 mW cm-2) results in a photocurrent that reaches 52 µA cm-2 at -0.2 V vs Ag/AgCl in the presence of p-toluenesulfonic acid (0.1 M), with Faradaic efficiencies of H2 production up to 85 ± 5% after 2.5 h without photoelectrode degradation. This work presents the first single-molecule photocatalyst, acting as both the light absorber and catalytic center on NiO, able to generate hydrogen from acidic solutions with red light when anchored to a p-type semiconductor, providing a promising new system for solar fuel production.
RESUMO
Low-dimensional organic-inorganic halide perovskites have attracted interest for their properties in exciton dynamics, broad-band emission, magnetic spin selectivity. However, there is no quantitative model for predicting the structure-directing effect of organic cations on the dimensionality of these low-dimensional perovskites. Here, we report a machine learning (ML)-assisted approach to predict the dimensionality of lead iodide-based perovskites. A literature review reveals 86 reported amines that are classified into "2D"-forming and "non-2D"-forming based on the dimensionality of their perovskites. Machining learning models were trained and tested based on the classification and descriptor features of these ammonium cations. Four structural features, including steric effect index, eccentricity, largest ring size, and hydrogen-bond donor, have been identified as the key controlling factors. On the basis of these features, a quantified equation is created to calculate the probability of forming 2D perovskite for a selected amine. To further illustrate its predicting capability, the built model is applied to several untested amines, and the predicted dimensionality is verified by growing single crystals of perovskites from these amines. This work represents a step toward predicting the crystal structures of low dimensional hybrid halide perovskites using ML as a tool.