Abstract
Identification of active sites is one of the main obstacles to rational design of catalysts for diverse applications. Fundamental insight into the identification of the structure of active ...sites and structural contributions for catalytic performance are still lacking. Recently, X-ray absorption spectroscopy (XAS) and density functional theory (DFT) provide important tools to disclose the electronic, geometric and catalytic natures of active sites. Herein, we demonstrate the structural identification of Zn-N
2
active sites with both experimental/theoretical X-ray absorption near edge structure (XANES) and extended X-ray absorption fine structure (EXAFS) spectra. Further DFT calculations reveal that the oxygen species activation on Zn-N
2
active sites is significantly enhanced, which can accelerate the reduction of oxygen with high selectivity, according well with the experimental results. This work highlights the identification and investigation of Zn-N
2
active sites, providing a regular principle to obtain deep insight into the nature of catalysts for various catalytic applications.
Apocrine carcinoma is a rare breast cancer subtype. As such, the genomic characteristics of apocrine carcinoma with triple negative immunohistochemical results (TNAC), which has been treated as ...triple negative breast cancer (TNBC), have not been revealed. In this study, we evaluated the genomic characteristics of TNAC compared to TNBC with low Ki-67 (LK-TNBC). In the genetic analysis of 73 TNACs and 32 LK-TNBCs, the most frequently mutated driver gene in TNAC was TP53 (16/56, 28.6%), followed by PIK3CA (9/56, 16.1%), ZNF717 (8/56, 14.3%), and PIK3R1 (6/56, 10.71%). Mutational signature analysis showed enrichment of defective DNA mismatch repair (MMR)-related signatures (SBS6 and SBS21) and the SBS5 signature in TNAC, whereas an APOBEC activity-associated mutational signature (SBS13) was more prominent in LK-TNBC (Student's t test, p < 0.05). In intrinsic subtyping, 38.4% of TNACs were classified as luminal A, 27.4% as luminal B, 26.0% as HER2-enriched (HER2-E), 2.7% as basal, and 5.5% as normal-like. The basal subtype was the most dominant subtype (43.8%) in LK-TNBC (p < 0.001), followed by luminal B (21.9%), HER2-E (21.9%), and luminal A (12.5%). In the survival analysis, TNAC had a five-year disease-free survival (DFS) rate of 92.2% compared to 59.1% for LK-TNBC (P = 0.001) and a five-year overall survival (OS) rate of 95.3% compared to 74.6% for LK-TNBC (P = 0.0099). TNAC has different genetic characteristics and better survival outcomes than LK-TNBC. In particular, normal-like and luminal A subtypes in TNAC have much better DFS and OS than other intrinsic subtypes. Our findings are expected to impact medical practice for patients diagnosed with TNAC.
Glioblastoma stem cells (GSCs), which are identified as subpopulation of CD133+/ALDH1+, are known to show resistance to the most of chemotherapy and radiation therapy, leading to the recurrence of ...tumor in glioblastoma multiforme (GBM) patients. Also, delivery of temozolomide (TMZ), a mainline treatment of GBM, to the GBM site is hampered by various barriers including the blood-brain barrier (BBB). A dual-targeting immunoliposome encapsulating TMZ (Dual-LP-TMZ) was developed by using angiopep-2 (An2) and anti-CD133 monoclonal antibody (CD133 mAb) for BBB transcytosis and specific delivery to GSCs, respectively. The size, zeta potential and drug encapsulation efficiency of Dual-LP-TMZ were 203.4nm in diameter, −1.6mV and 99.2%, respectively. The in vitro cytotoxicity of Dual-LP-TMZ against U87MG GSCs was increased by 425- and 181-folds when compared with that of free TMZ and non-targeted TMZ liposome (LP-TMZ) (10.3μM vs. 4380μM and 1869μM in IC50, respectively). Apoptosis and anti-migration ability of Dual-LP-TMZ in U87MG GSCs were also significantly enhanced comparing with those of free TMZ or LP-TMZ. In vivo study clearly showed a significant reduction in tumor size after intravenous administrations of Dual-LP-TMZ to the orthotopically-implanted brain tumor mice when compared with free TMZ or LP-TMZ. Increased life span (ILS) and median survival time (MST) of tumor-bearing mice were also increased when treated with Dual-LP-TMZ (211.2% in ILS and 49.2days in MST) than with free TMZ (0% in ILS and 23.3day in MST). These data indicate that conjugation of both An2 peptide and CD133 mAb to TMZ-encapsulating liposome is very effective in delivering the TMZ to GSCs via BBB, suggesting a potential use of Dual-LP-TMZ as a therapeutic modality for GBM.
Dual-targeting immunoliposome using angiopep-2 peptide and anti-CD133 antibody for the therapy of glioblastoma multiforme. Display omitted
Although medical requirements are urgent, no effective intervention has been proven for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). To facilitate the development of new therapeutics, ...we systematically reviewed the randomized controlled trials (RCTs) for CFS/ME to date.
RCTs targeting CFS/ME were surveyed using two electronic databases, PubMed and the Cochrane library, through April 2019. We included only RCTs that targeted fatigue-related symptoms, and we analyzed the data in terms of the characteristics of the participants, case definitions, primary measurements, and interventions with overall outcomes.
Among 513 potentially relevant articles, 55 RCTs met our inclusion criteria; these included 25 RCTs of 22 different pharmacological interventions, 28 RCTs of 18 non-pharmacological interventions and 2 RCTs of combined interventions. These studies accounted for a total of 6316 participants (1568 males and 4748 females, 5859 adults and 457 adolescents). CDC 1994 (Fukuda) criteria were mostly used for case definitions (42 RCTs, 76.4%), and the primary measurement tools included the Checklist Individual Strength (CIS, 36.4%) and the 36-item Short Form health survey (SF-36, 30.9%). Eight interventions showed statistical significance: 3 pharmacological (Staphypan Berna, Poly(I):poly(C
U) and CoQ
+ NADH) and 5 non-pharmacological therapies (cognitive-behavior-therapy-related treatments, graded-exercise-related therapies, rehabilitation, acupuncture and abdominal tuina). However, there was no definitely effective intervention with coherence and reproducibility.
This systematic review integrates the comprehensive features of previous RCTs for CFS/ME and reflects on their limitations and perspectives in the process of developing new interventions.
Monoidal categorification of cluster algebras KANG, SEOK-JIN; KASHIWARA, MASAKI; KIM, MYUNGHO ...
Journal of the American Mathematical Society,
04/2018, Volume:
31, Issue:
2
Journal Article
Peer reviewed
Open access
We prove that the quantum cluster algebra structure of a unipotent quantum coordinate ring A_q(\mathfrak{n}(w)), associated with a symmetric Kac-Moody algebra and its Weyl group element w, admits a ...monoidal categorification via the representations of symmetric Khovanov-Lauda-Rouquier algebras. In order to achieve this goal, we give a formulation of monoidal categorifications of quantum cluster algebras and provide a criterion for a monoidal category of finite-dimensional graded R-modules to become a monoidal categorification, where R is a symmetric Khovanov-Lauda-Rouquier algebra. Roughly speaking, this criterion asserts that a quantum monoidal seed can be mutated successively in all the directions, once the first-step mutations are possible. Then, we show the existence of a quantum monoidal seed of A_q(\mathfrak{n}(w)) which admits the first-step mutations in all the directions. As a consequence, we prove the conjecture that any cluster monomial is a member of the upper global basis up to a power of q^{1/2}. In the course of our investigation, we also give a proof of a conjecture of Leclerc on the product of upper global basis elements.
This cohort study aimed to investigate the factors associated with noninvasive positive pressure ventilation adherence and assess the long-term effects of noninvasive positive pressure ventilation ...adherence in patients with amyotrophic lateral sclerosis (ALS).
The medical records of patients with ALS admitted to a tertiary hospital for noninvasive positive pressure ventilation initiation were retrospectively reviewed. Pulmonary function parameters, variables of blood gas analysis, the site of symptom onset, the time from onset and diagnosis to noninvasive positive pressure ventilation application, ALS Functional Rating Scale-Revised, neurophysiological index, and the length of hospital stay were evaluated. The adherence to noninvasive positive pressure ventilation was defined as the use of noninvasive positive pressure ventilation for ≥ 2 h/day or ≥ 4 h/day. The correlations between noninvasive positive pressure ventilation adherence or length of hospital stay and other clinical parameters were analyzed.
Fifty-one patients with ALS were included in the study. The time from onset and diagnosis to NIPPV application was reduced by 16 months in the adherent group than that in the non-adherent group; however, the parameters of blood gas analysis and pulmonary function tests did not differ significantly between the groups. Furthermore, the neurophysiological index of the abductor digiti minimi muscle was higher by 4.05 in the adherent group than that in the non-adherent group. The adherence to noninvasive positive pressure ventilation prolonged tracheostomy-free survival compared to that of non-adherence. Desaturation events, lower forced vital capacity, last pCO2, bicarbonate, and base excess, and higher differences in pCO2, were associated with an increase in the length of hospital stay.
Noninvasive positive pressure ventilation application shortly after symptom onset and ALS diagnosis in patients with CO2 retention and reduced forced vital capacity can be considered for successful adherence. Adherence to noninvasive positive pressure ventilation may result in reduced tracheostomy conversion rates and prolonged tracheostomy-free survival.
On the basis of the benefits of frontline radiation in early-stage, extranodal, natural killer (NK)/T-cell lymphoma (ENKTL), we conducted a phase II trial of concurrent chemoradiotherapy (CCRT) ...followed by three cycles of etoposide, ifosfamide, cisplatin, and dexamethasone (VIPD).
Thirty patients with newly diagnosed, stages IE to IIE, nasal ENKTL received CCRT (ie radiation 40 to 52.8 Gy and cisplatin 30 mg/m(2) weekly). Three cycles of VIPD (etoposide 100 mg/m(2) days 1 through 3, ifosfamide 1,200 mg/m(2) days 1 through 3, cisplatin 33 mg/m(2) days 1 through 3, and dexamethasone 40 mg days 1 through 4) were scheduled after CCRT.
All patients completed CCRT, which resulted in 100% response that included 22 complete responses (CRs) and eight partial responses (PRs). The CR rate after CCRT was 73.3% (ie, 22 of 30 responses; 95% CI, 57.46 to 89.13). Twenty-six of 30 patients completed the planned three cycles of VIPD, whereas four patients did not because they withdrew (n = 2) or because they had an infection (n = 2). The overall response rate and the CR rate were 83.3% (ie; 25 of 30 responses; 95% CI, 65.28 to 94.36) and 80.0% (ie, 24 of 30 responses; 95% CI, 65.69 to 94.31), respectively. Only one patient experienced grade 3 toxicity during CCRT (nausea), whereas 12 of 29 patients experienced grade 4 neutropenia. The estimated 3-year, progression-free and overall survival rates were 85.19% (95% CI, 72.48 to 97.90) and 86.28% (95% CI, 73.97 to 98.59), respectively.
Patients with newly diagnosed, stages IE to IIE, nasal ENKTL are best treated with frontline CCRT.
Single atom catalysts (SACs) are of great importance for oxygen reduction, a critical process in renewable energy technologies. The catalytic performance of SACs largely depends on the structure of ...their active sites, but explorations of highly active structures for SAC active sites are still limited. Herein, we demonstrate a combined experimental and theoretical study of oxygen reduction catalysis on SACs, which incorporate M−N3C1 site structure, composed of atomically dispersed transition metals (e.g., Fe, Co, and Cu) in nitrogenated carbon nanosheets. The resulting SACs with M−N3C1 sites exhibited prominent oxygen reduction catalytic activities in both acidic and alkaline media, following the trend Fe−N3C1 > Co−N3C1 > Cu−N3C1. Theoretical calculations suggest the C atoms in these structures behave as collaborative adsorption sites to M atoms, thanks to interactions between the d/p orbitals of the M/C atoms in the M−N3C1 sites, enabling dual site oxygen reduction.
Isolated M−N3C1 active sites were engineered into the single atom catalysts for efficient oxygen reduction catalysis. Theoretical calculations proposed that the M/C atoms in the active sites served as dual adsorption sites, enabling more efficient collaborative catalysis.
A highly stretchable hybrid nanogenerator has been developed using a micro‐patterned piezoelectric polymer P(VDF‐TrFE), PDMS‐CNT composite, and graphene nanosheets. Mechanical and thermal energies ...are simultaneously harvested from a single cell of the device. The hybrid nanogenerator exhibits high robustness behavior even after 30% stretching and generates very stable piezoelectric and pyroelectric power outputs due to micro‐pattern designing.
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