SFTS virus (SFTSV) is a novel bunyavirus that causes severe fever with thrombocytopenia syndrome (SFTS), an emerging infectious disease that occurred in China in recent years, with an average case ...fatality rate of 10–12%. Intervention in the early clinical stage is the most effective measure to reduce the mortality rate of disease. To elucidate the natural course of and immune mechanisms associated with the pathogenesis of SFTSV, 59 laboratory-confirmed SFTS patients in the acute phase, who were hospitalized between October 2010 and September 2011, were enrolled in this study, and the patients sera were dynamically collected and tested for SFTSV viral RNA load, 34 cytokines or chemokines and other related laboratory parameters. All clinical diagnostic factors in the acute phase of SFTS were evaluated and assessed. The study showed that the severity of the disease in 11 (18.6%) patients was associated with abdominal pain (p 0.007; OR = 21.95; 95% CI, 2.32–208.11) and gingival bleeding (p 0.001; OR = 122.11; 95% CI, 6.41–2328). The IP-10, TNF-α, IL-6, IL-10, granzyme B and HSP70 levels were higher over the 7–8 days in severe cases, accompanied by altered AST, CK and LDH levels. HSP70 (p 0.012; OR = 8.29; 95% CI, 1.58–43.40) was independently correlated with the severity of the early acute phase of SFTSV infection. The severity of SFTS can be predicted based on the presence of symptoms such as abdominal pain and gingival bleeding and on the level of HSP70 in the acute phase of the disease.
Efficient organic light‐emitting diodes (OLEDs) incorporating IrIII bis(4,6‐difluorophenylpyridinato)‐3‐(trifluoromethyl)‐5‐ (pyridin‐2‐yl)‐1,2,4‐triazolate (FIrtaz) and IrIII ...bis(4,6‐difluorophenylpyridinato)‐5‐(pyridin‐2‐yl)‐1H‐tetrazolate (FIrN4) demonstrate higher‐purity blue‐light emission than the long‐known IrIII bis(4,6‐difluorophenylpyridinato)picolate (FIrpic) phosphorophore. New host materials with higher glass‐transition temperatures were also found to enhance the OLED performance.
Summary Objective To evaluate the effects of PTH(1-34) on cartilage, subchondral bone mass and structure in medial meniscectomized guinea pigs and compare them to those of celecoxib (CLX). Method ...Forty-eight 3-month-old male Hartley albino guinea pigs received either sham or medial meniscectomy (MNX) operations. One week after the procedure, meniscectomized animals began 12 weeks of treatment by oral administration of CLX (20 mg/kg, daily), subcutaneous injection of PTH (1-34) (24 μg/kg, 5 days/week), or normal saline for MNX group. All animals were euthanized 12 weeks later, cartilage degeneration and subchondral bone micro-architecture was analyzed. Results OARSI scores indicated cartilage degeneration was partially inhibited by either CLX or PTH(1-34). Cartilage was significantly thicker in PTH(1-34)-treated animals than in CLX-treated animals. Both CLX and PTH(1-34) treatment were associated with lower ADAMTS-4 and periostin expression than MNX. MMP-13 expression in PTH(1-34) group was significantly lower than that in CLX group. However, AGG expression and the ratio of Col-II/MMP-13 expression in PTH(1-34) group were significantly higher than in the CLX group. Micro-CT analysis showed BMD, BV/TV, and Tb.Th levels to be significantly lower in the MNX group and CLX groups than in the sham group, but these parameters were significantly higher in the PTH(1-34) group than in either the MNX group or CLX group. Conclusions Both CLX and PTH(1-34) exhibits protective effects on cartilage degeneration in meniscectomized guinea pigs. However, PTH(1-34) exhibited superior performance to CLX not only in metabolism of cartilage tissue but also in maintenance of subchondral bone micro-architecture.
Abnormal remodeling of subchondral bone (SB) induced by estrogen deficiency has been shown to be involved in osteoarthritis (OA). Raloxifene (RAL) is commonly used to treat postmenopausal ...osteoporosis (OP). However, little is known about its effects on OA combined with estrogen deficiency. This study was performed to evaluate the efficacy of RAL on patella baja-induced patellofemoral joint OA (PFJOA) in an ovariectomized rat model.
Patellar ligament shortening (PLS) and ovariectomy (OVX) were performed simultaneously in 3-month-old female Sprague–Dawley rats, which were treated with RAL (10 mg/kg/day) or vehicle at 72 h postoperatively for 10 weeks. PFJOA was assessed by immunohistochemistry (IHC), real-time polymerase chain reaction (PCR), tartrate-resistant acid phosphatase (TRAP) staining, enzyme-linked immunosorbent assay (ELISA), micro-computed tomography (μCT), histomorphology and behavioral analyses.
X-ray examinations showed that patella baja was successfully established by PLS. Histomorphological analysis revealed that PFJOA was significantly exacerbated by OVX and markedly alleviated by RAL. Moreover, RAL improved cartilage metabolism by decreasing MMP-13, ADAMTS-4, and caspase-3 and increasing Col-II and aggrecan at both the protein and mRNA levels. Furthermore, RAL markedly improved bone mass and SB microarchitecture and reduced osteoclast numbers and the serum osteocalcin and CTX-I levels. Although RAL showed a trend toward reducing pain sensitivity based on mechanical allodynia testing, this result was not statistically significant.
These findings demonstrate that RAL treatment retards PFJOA progression in an ovariectomized rat model, suggesting that it may be a potential candidate for amelioration of the progression of PFJOA accompanied by postmenopausal OP.
Semiconductors are the basis of many vital technologies such as electronics, computing, communications, optoelectronics, and sensing. Modern semiconductor technology can trace its origins to the ...invention of the point contact transistor in 1947. This demonstration paved the way for the development of discrete and integrated semiconductor devices and circuits that has helped to build a modern society where semiconductors are ubiquitous components of everyday life. A key property that determines the semiconductor electrical and optical properties is the bandgap. Beyond graphene, recently discovered two-dimensional (2D) materials possess semiconducting bandgaps ranging from the terahertz and mid-infrared in bilayer graphene and black phosphorus, visible in transition metal dichalcogenides, to the ultraviolet in hexagonal boron nitride. In particular, these 2D materials were demonstrated to exhibit highly tunable bandgaps, achieved via the control of layers number, heterostructuring, strain engineering, chemical doping, alloying, intercalation, substrate engineering, as well as an external electric field. We provide a review of the basic physical principles of these various techniques on the engineering of quasi-particle and optical bandgaps, their bandgap tunability, potentials and limitations in practical realization in future 2D device technologies.
CTONG0806 assessed the efficacy of pemetrexed versus gefitinib as second-line treatment in advanced nonsquamous nonsmall-cell lung cancer (NSCLC) harboring wild-type epidermal growth factor receptor ...(EGFR).
Patients with locally advanced or metastatic nonsquamous NSCLC harboring wild-type EGFR, detected by direct sequencing, and previously treated with platinum-based chemotherapy were randomized to receive gefitinib (250 mg/day) orally or pemetrexed (500 mg/m2) i.v. on day 1 of a 21-day cycle until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS). The Independent Review Committee (IRC) evaluated all pictorial data.
From February 2009 to August 2012, 161 patients were enrolled, and 157 were assessable (81 in the gefitinib arm, 76 in the pemetrexed arm). Baseline characteristics were balanced between the two arms. The median PFSs were 4.8 versus 1.6 months in the pemetrexed and gefitinib arms, respectively hazard ratio (HR) 0.54, 95% confidence interval (CI) 0.40–0.75, P < 0.001 as confirmed by IRC evaluation (5.6versus 1.7 months, HR 0.53, 95% CI 0.38–0.75, P < 0.001). The median overall survival (OS) showed a trend of superiority in the pemetrexed arm (12.4 versus 9.6 months, HR 0.72, 95% CI 0.49–1.04, P = 0.077). Quality-of-life assessment showed no marked difference between the arms. No unexpected adverse events were found. Of 108 patients with sufficient DNA samples, EGFR mutation status was re-tested by Scorpion amplification refractory mutation system (ARMS); 32 (29.6%) tested positive (19 in the pemetrexed arm, 13 in the gefitinib arm; median PFS: 8.1 versus 7.0 months, HR 0.94, 95% CI 0.43–2.08, P = 0.877).
CTONG0806 is the first trial to show significant improvement in PFS and an improved OS trend with pemetrexed compared with gefitinib as second-line setting treatment of EGFR wild-type advanced nonsquamous NSCLC. ARMS is superior to direct sequencing in excluding false-negative patients.
NCT00891579.
Electrochemical water splitting into hydrogen and oxygen is a promising technology for sustainable energy storage. The development of earth-abundant transition metal phosphides (TMPs) to catalyze the ...hydrogen evolution reaction (HER) and TMP-derived oxy-hydroxides to catalyze the oxygen evolution reaction (OER) has recently drawn considerable attention. However, most monolithically integrated metal phosphide electrodes are prepared by laborious multi-step methods and their operational stability at high current densities has been rarely studied. Herein, we report a novel vapor-solid synthesis of single-crystalline cobalt phosphide nanowires (CoP NWs) on a porous Co foam and demonstrate their use in overall water splitting. The CoP NWs grown on the entire surface of the porous Co foam ligaments have a large aspect ratio, and hence are able to provide a large catalytically accessible surface over a given geometrical area. Comprehensive investigation shows that under the OER conditions CoP NWs are progressively and conformally converted to CoOOH through electrochemical
oxidation/dephosphorization; the latter serving as an active species to catalyze the OER. The
oxidized electrode shows exceptional electrocatalytic performance for the OER in 1.0 M KOH, delivering 100 mA cm
at an overpotential (
) of merely 300 mV and a small Tafel slope of 78 mV dec
as well as excellent stability at various current densities. Meanwhile, the CoP NW electrode exhibits superior catalytic activity for the HER in the same electrolyte, affording -100 mA cm
at
= 244 mV and showing outstanding stability. An alkaline electrolyzer composed of two symmetrical CoP NW electrodes can deliver 10 and 100 mA cm
at low cell voltages of 1.56 and 1.78 V, respectively. The CoP NW electrolyzer demonstrates exceptional long-term stability for overall water splitting, capable of working at 20 and 100 mA cm
for 1000 h without obvious degradation.
GlcNAcylation is a dynamic post-translational modification that diversifies the proteome. Its dysregulation is associated with neurological disorders that impair cognitive function, and yet ...identification of phenotype-relevant candidate substrates in a brain-region specific manner remains unfeasible. By combining an
GlcNAc binding activity derived from
OGA (
OGA) with TurboID proximity labeling in
, we developed an
GlcNAcylation profiling tool that translates
GlcNAc modification into biotin conjugation for tissue-specific candidate substrates enrichment. We mapped the
GlcNAc interactome in major brain regions of
and found that components of the translational machinery, particularly ribosomal subunits, were abundantly
GlcNAcylated in the mushroom body of
brain. Hypo-
GlcNAcylation induced by ectopic expression of active
OGA in the mushroom body decreased local translational activity, leading to olfactory learning deficits that could be rescued by dMyc overexpression-induced increase of protein synthesis. Our study provides a useful tool for future dissection of tissue-specific functions of
GlcNAcylation in
, and suggests a possibility that
GlcNAcylation impacts cognitive function via regulating regional translational activity in the brain.
An increasing number of genetic variants have been implicated in autism spectrum disorders (ASDs), and the functional study of such variants will be critical for the elucidation of autism ...pathophysiology. Here, we report a de novo balanced translocation disruption of TRPC6, a cation channel, in a non-syndromic autistic individual. Using multiple models, such as dental pulp cells, induced pluripotent stem cell (iPSC)-derived neuronal cells and mouse models, we demonstrate that TRPC6 reduction or haploinsufficiency leads to altered neuronal development, morphology and function. The observed neuronal phenotypes could then be rescued by TRPC6 complementation and by treatment with insulin-like growth factor-1 or hyperforin, a TRPC6-specific agonist, suggesting that ASD individuals with alterations in this pathway may benefit from these drugs. We also demonstrate that methyl CpG binding protein-2 (MeCP2) levels affect TRPC6 expression. Mutations in MeCP2 cause Rett syndrome, revealing common pathways among ASDs. Genetic sequencing of TRPC6 in 1041 ASD individuals and 2872 controls revealed significantly more nonsynonymous mutations in the ASD population, and identified loss-of-function mutations with incomplete penetrance in two patients. Taken together, these findings suggest that TRPC6 is a novel predisposing gene for ASD that may act in a multiple-hit model. This is the first study to use iPSC-derived human neurons to model non-syndromic ASD and illustrate the potential of modeling genetically complex sporadic diseases using such cells.
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