A vanadium pentoxide electrode is prepared in the amorphous form (a-V2O5), and its electrode performances are compared to those for its crystalline counterpart (c-V2O5). The a-V2O5 electrode ...outperforms c-V2O5 in several ways. First, it is free from irreversible phase transitions and Li trapping, which evolve in c-V2O5, probably due to the lack of interactions between the inserted Li+ ions/electrons and V2O5 matrix. Second, the absence of Li trapping allows a reversible capacity amounting to >600 mA h g–1, which is larger than that given by c-V2O5. Third, it shows an excellent rate property. The notably high reversible capacity and rate capability seem to be due to Li storage at vacant sites that are ill-defined but numerous in a-V2O5, which Li+ ions can easily access. However, irreversible capacity of a-V2O5 is appreciable in the first cycle due to a parasitic Li reaction with surface hydroxyl groups. Treatment with n-butyllithium can suppress the irreversible capacity by removing the surface hydroxyl groups.
In this study, (pentafluorophenylpropyl)trimethoxysilane (PFPPS) is grafted on a nickel-doped manganese spinel (LiNi0.5Mn1.5O4, LNMO) surface to suppress the failure modes in the 5-V positive ...electrode; electrolyte oxidation/film deposition, acid generation, and metal (Ni and Mn) dissolution. Vapor-phase molecular layer deposition is used to deposit a uniformly covered PFPPS layer on the LNMO surface. When the Li/LNMO cell is cycled at 3.5–4.9 V (vs. Li/Li+), the PFPPS moiety on the LNMO surface remains intact (not oxidized) under the highly oxidizing condition. Several beneficial features are observed with the PFPPS grafting. The oxidative electrolyte decomposition is mitigated, which increases the Coulombic efficiency of the Li/LNMO cell. Consequently, the surface film deposition and cell polarization are reduced, improving the capacity retention. Moreover, the acid generation and metal dissolution are also mitigated.
•PFPPS monolayer is grafted uniformly on LNMO surface.•PFPPS layer is stable against oxidation over the working voltage of LNMO.•PFPPS layer suppresses electrolyte oxidation, raising Coulombic efficiency.•PFPPS layer reduces cell polarization, improving capacity retention.
Margin status is one of the most significant prognostic factors after curative surgery for middle bile duct (MBD) cancer. Bile duct resection (BDR) is commonly converted to pancreaticoduodenectomy ...(PD) to achieve R0 resection. Additionally, adjuvant treatment is actively performed after surgery to improve survival. However, the wider the range of surgery, the higher the chance of complications; this, in turn, makes adjuvant treatment impossible. Nevertheless, no definitive surgical strategy considers the possible complication rates and subsequent adjuvant treatment. We aimed to investigate the appropriate surgical type considering the margin status, complications, and adjuvant treatment in MBD cancer.
From 2008 to 2017, 520 patients diagnosed with MBD cancer at the Samsung Medical Center were analyzed retrospectively according to the operation type, margin status, complications, and adjuvant treatment. The R1 group was defined as having a carcinoma margin.
The 5-year survival rate for patients who underwent R0 and R1 resection was 54.4% and 33.3%, respectively (
0.131). Prognostic factors affecting the overall survival were the age, preoperative CA19-9 level, T stage, and N stage, but not the operation type, margin status, complications, or adjuvant treatment. The complication rates were 11.5% and 29.8% in the BDR and PD groups, respectively (
< 0.001). We observed no significant difference in the adjuvant treatment ratio according to complications (
= 0.675). Patients with PD who underwent R0 resection and could not undergo chemotherapy because of complications reported better survival rates than those with BDR who underwent R1 resection after adjuvant treatment (
= 0.003).
The survival outcome of patients with R1 margins who underwent BDR did not match those with R0 margins after PD, even after adjuvant treatment. Due to improvements in surgical techniques and the ability to resolve complications, surgical complications exert a marginal effect on survival. Therefore, surgeons should secure R0 margins to achieve the best survival outcomes.
Spinal muscular atrophy (SMA) is caused by homozygous survival of motor neurons 1 (SMN1) gene deletion, leaving a duplicate gene, SMN2, as the sole source of SMN protein. However, a defect in SMN2 ...splicing, involving exon 7 skipping, results in a low level of functional SMN protein. Therefore, the upregulation of SMN protein expression from the SMN2 gene is generally considered to be one of the best therapeutic strategies to treat SMA. Most of the SMA drug discovery is based on synthetic compounds, and very few natural compounds have been explored thus far. Here, we performed an unbiased mechanism-independent and image-based screen of a library of microbial metabolites in SMA fibroblasts using an SMN-specific immunoassay. In doing so, we identified brefeldin A (BFA), a well-known inhibitor of ER-Golgi protein trafficking, as a strong inducer of SMN protein. The profound increase in SMN protein was attributed to, in part, the rescue of the SMN2 pre-mRNA splicing defect. Intriguingly, BFA increased the intracellular calcium concentration, and the BFA-induced exon 7 inclusion of SMN2 splicing, was abrogated by the depletion of intracellular calcium and by the pharmacological inhibition of calcium/calmodulin-dependent kinases (CaMKs). Moreover, BFA considerably reduced the expression of Tra2-β and SRSF9 proteins in SMA fibroblasts and enhanced the binding of PSF and hnRNP M to an exonic splicing enhancer (ESE) of exon 7. Together, our results demonstrate a significant role for calcium and its signaling on the regulation of SMN splicing, probably through modulating the expression/activity of splicing factors.
According to the 2016 National Comprehensive Cancer Network (NCCN) guidelines, patients with borderline resectable pancreatic cancer (BRPC) should receive chemotherapy as the first-line treatment. ...This study examined the real-world survival benefits of modifying BRPC treatment guidelines. Patients treated for BRPC at a single institution from 2013 to 2015 (pre-guideline group) and 2017 to 2019 (post-guideline group) were retrospectively reviewed. According to the treatment method used, patients were classified into upfront surgery (US), surgery after neoadjuvant treatment (NAT), and chemotherapy only (CO) groups. Overall survival (OS) was compared according to period and treatment type. Factors associated with OS were analyzed using a Cox regression model. Among the 165 patients, 63 were in the pre-guideline group and 102 patients were in the post-guideline group. The median OS was significantly improved in the post-guideline group compared to the pre-guideline group (29 vs. 13 months, p < 0.001). According to the treatment method, the median OS of the NAT group was significantly longer than that of the US and CO groups (40 vs. 16 vs. 15 months, respectively, p < 0.001). In multivariate analysis, tumor size, differentiation, NAT, and perineural invasion were significant prognostic factors. NAT is an important treatment option for BRPC and increased patient survival in the real world.
Diacylglycerol acyltransferases (DGATs) have a crucial role in the biosynthesis of triacylglycerol (TG), the major storage form of metabolic energy in eukaryotic organisms. Even though DGAT2, one of ...two distinct DGATs, has a vital role in TG biosynthesis, little is known about the regulation of DGAT2 activity. In this study, we examined the role of cysteine and its oxidation in the enzymatic activity of human DGAT2 in vitro. Human DGAT2 activity was considerably inhibited not only by thiol-modifying reagents (NEM and IA) but also by ROS-related chemicals (H2O2 and β-lapachone), while human DGAT1 and GPAT1 were little affected. Particularly, ROS-related chemicals concomitantly induced intermolecular disulfide crosslinking of human DGAT2. Both the oxidative inactivation and disulfide crosslinking were almost completely reversed by the treatment with DTT, a disulfide-reducing agent. These results clearly demonstrated the significant role of ROS-induced intermolecular crosslinking in the inactivation of human DGAT2 and also suggested DGAT2 as a redox-sensitive regulator in TG biosynthesis.
Enterovirus 71 (EV71) is a major causative agent of hand-foot-mouth disease (HFMD) and also causes severe neurological complications, leading to fatality in young children. However, no effective ...therapy is currently available for the treatment of this infection.
We identified small-molecule inhibitors of EV71 from a screen of 968 Food and Drug Administration (FDA)-approved drugs, with which clinical application for EV71-associated diseases would be more feasible, using EV71 subgenomic replicon system. Primary hits were extensively evaluated for their antiviral activities in EV71-infected cells.
We identified micafungin, an echinocandin antifungal drug, as a novel inhibitor of EV71. Micafungin potently inhibits the proliferation of EV71 as well as the replication of EV71 replicon in cells with a low micromolar IC50 (~5 μM). The strong antiviral effect of micafungin on EV71 replicon and the result from time-of-addition experiment demonstrated a targeting of micafungin on virion-independent intracellular process(es) during EV71 infection. Moreover, an extensive analysis excluded the involvement of 2C and 3A proteins, IRES-dependent translation, and also that of polyprotein processing in the antiviral effect of micafungin.
Our research revealed a new indication of micafungin as an effective inhibitor of EV71, which is the first case reporting antiviral activity of micafungin, an antifungal drug.
Purpose: The purpose of this study was to determine whether a higher Injury Severity Score (ISS) could serve as an indicator of splenectomy in patients with traumatic splenic lacerations. Methods: A ...total of 256 cases of splenic laceration were collected from January 1, 2005 to December 31, 2018. After the application of exclusion criteria, 105 were eligible for this study. Charts were reviewed for demographic characteristics, initial vital signs upon presentation to the emergency room, Glasgow Coma Scale, computed tomography findings, ISS, and treatment strategies. The cases were then divided into nonsplenectomy and splenectomy groups for analysis.Results: When analyzed with the chi-square test and t-test, splenectomy was associated with a systolic blood pressure lower than 90 mmHg, a Glasgow Coma Scale score lower than 13, active bleeding found on computed tomography, a splenic laceration grade greater than or equal to 4, and an ISS greater than 15 at presentation. However, in multivariate logistic regression analysis, only active bleeding on computed tomography showed a statistically significant relationship (P=0.014).Conclusions: Although ISS failed to show a statistically significant independent relationship with splenectomy, it may still play a supplementary role in traumatic splenic injury management. KCI Citation Count: 0
Purpose: The purpose of this study was to determine whether a higher Injury Severity Score (ISS) could serve as an indicator of splenectomy in patients with traumatic splenic lacerations. Methods: A ...total of 256 cases of splenic laceration were collected from January 1, 2005 to December 31, 2018. After the application of exclusion criteria, 105 were eligible for this study. Charts were reviewed for demographic characteristics, initial vital signs upon presentation to the emergency room, Glasgow Coma Scale, computed tomography findings, ISS, and treatment strategies. The cases were then divided into nonsplenectomy and splenectomy groups for analysis. Results: When analyzed with the chi-square test and t-test, splenectomy was associated with a systolic blood pressure lower than 90 mmHg, a Glasgow Coma Scale score lower than 13, active bleeding found on computed tomography, a splenic laceration grade greater than or equal to 4, and an ISS greater than 15 at presentation. However, in multivariate logistic regression analysis, only active bleeding on computed tomography showed a statistically significant relationship (P=0.014). Conclusions: Although ISS failed to show a statistically significant independent relationship with splenectomy, it may still play a supplementary role in traumatic splenic injury management.
Dependence of taper angle of the surface plasmon resonance (SPR)-based fiber optic sensor on the SPR absorption and sensitivity was investigated. The SPR wavelength was found to increase from 700nm ...to 1200nm with the increase of the refractive index of the surrounding oils from 1.404 to 1.434. The SPR sensitivity increased with the increase of metal-coated taper angle (Ω) from 0.07° to 1.86° by changing the down/up tapering length or waist diameter. The absorption intensity of the SPR spectrum was found to decrease and the FWHM was broadened with the increase of refractive index of the index matching oils (n=1.404–1.434) due to the leakage of the power fraction of guided rays into the surrounding medium and the spatial spreading and scattering of the conduction electrons, respectively.
•We fabricated the SPR-based fiber optic sensor with metal-coated taper regions.•The SPR sensor probe was tapered from 0.07° to 1.86° with great precision.•As the taper angle increased, the SPR sensitivity increased.•The intensity of the SPR absorbance was 3 times larger than that of the reference.•The average SPR absorbance within R.I. did not seem to correlate with taper angle.
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