Abstract Previous data demonstrate that traumatic brain injury (TBI) activates autophagy, and increases microtubule-associated protein 1 light chain 3 (LC3) immunostaining mainly in neurons. However, ...the role of autophagy in traumatic brain damage remains elusive. The aim of the present study was to investigate the autophagic mechanisms participating in traumatic brain injury. The autophagy inhibitors 3-methyladenine (3-MA) and bafliomycin A1 (BFA) were administered with a single i.c.v. injection before TBI. We first examined the protein levels of Beclin-1 and LC3 II, which have been found to promote autophagy previously. Immunoblotting analysis showed that 3-MA pretreatment reduced post-TBI Beclin-1 and LC3-II levels, and maintained p62/SQSTM1 (p62) levels. In addition, double immunolabeling showed that the increased punctate LC3-II dots colocalizing with Propidium Iodide (PI)-stained nuclei at 24 h after injury, were partially inhibited by 3-MA pretreatment. Furthermore, inhibition of autophagy could reduce TBI-induced cell injury assessed with i.p. injection of PI and lesion volume, and attenuate behavioral outcome evaluated by motor test and Morris water maze. The neuroprotective effects were associated with an inhibition on TBI-induced up-regulation of LC3, Beclin-1, cathepsin B, caspase-3 and the Beclin-1/Bcl-2 ratio. Taken together, these data imply that the autophagy pathway is involved in the pathophysiologic responses after TBI, and inhibition of this pathway may help attenuate traumatic damage and functional outcome deficits.
In order to determine the orbital characters on the various Fermi surface pockets of the Fe-based superconductors Ba sub(0.6)K sub(0.4)Fe sub(2)As sub(2) and FeSe sub(0.45)Te sub(0.55), we introduce ...a method to calculate photoemission matrix elements. We compare our simulations to experimental data obtained with various experimental configurations of beam orientation and light polarization. We show that the photoemission intensity patterns revealed from angle-resolved photoemission spectroscopy measurements of Fermi surface mappings and energy-momentum plots along high-symmetry lines exhibit asymmetries carrying precious information on the nature of the states probed, information that is destroyed after the data symmetrization process often performed in the analysis of angle-resolved photoemission spectroscopy data. Our simulations are consistent with Fermi surfaces originating mainly from the dxy, dxz, and dyyz orbitals in these materials.
The interface between transition metal compounds provides a rich playground for emergent phenomena. Recently, significantly enhanced superconductivity has been reported for single-layer FeSe on ...Nb-doped SrTiO3 substrate. Yet it remains mysterious how the interface affects the superconductivity. Here we use in situ angle-resolved photoemission spectroscopy to investigate various FeSe-based heterostructures grown by molecular beam epitaxy, and uncover that electronic correlations and superconducting gap-closing temperature (Tg) are tuned by interfacial effects. Tg up to 75 K is observed in extremely tensile-strained single-layer FeSe on Nb-doped BaTiO3, which sets a record high pairing temperature for both Fe-based superconductor and monolayer-thick films, providing a promising prospect on realizing more cost-effective superconducting device. Moreover, our results exclude the direct correlation between superconductivity and tensile strain or the energy of an interfacial phonon mode, and highlight the critical and non-trivial role of FeSe/oxide interface on the high Tg, which provides new clues for understanding its origin.
Summary
Deficiency of CARD9 (caspase recruitment domain‐containing protein 9) has been reported in individuals with recurrent and invasive fungal infections. We report on a patient who first had ...Trichosporon asahii affecting the skin then Candida albicans infections involving the digestive tract and knee joint, along with elevated serum IgE. After stimulation with C. albicans, peripheral blood mononuclear cells of this patient produced less tumour necrosis factor‐α, interferon‐γ and interleukin‐17 than those of healthy controls. Furthermore, the serum IgE levels of this patient were positively correlated with the severity of fungal infection during the course of treatment. Sanger sequencing identified one homozygous frameshift mutation (p.D274fsX60) in CARD9. We further performed a review including 48 cases with CARD9 deficiency. According to the data published previously, CARD9‐deficient patients demonstrated obviously elevated IgE in serum (median 1300 IU mL−1), which could distinguish them from otherwise healthy people with fungal infections (area under the curve 0·94, P < 0·001). Patients carrying the mutations Q289X and Q295X had a higher mortality rate (24% vs. 0%, P < 0·05). Patients with the mutations R18W, R35Q, R70W, G72S or Y91H in the CARD domain, and the nonsense mutation Q295X in the coiled‐coil domain, seemed to be more prone to Candida infections (90% vs. 20%, P < 0·005) and central nervous system infections (60% vs. 12%, P < 0·005).
What's already known about this topic?
CARD9 deficiency is a rare autosomal recessive genetic defect in T helper 17 immunity, resulting in susceptibility to recurrent and invasive fungal infections.
Patients with genetic defects in T helper 17 immunity are prone to hyper‐IgE syndrome.
What does this study add?
We report a patient with CARD9 p.D274fsX60 mutation manifested as multiple organs infections by Trichosporon asahii and Candida albicans.
This study enriches the phenotypic spectrum of CARD9 deficiency.
IgE level seems to be a possible clue for diagnosis or therapeutic effect of fungal infection in CARD9‐deficient patients.
Aim
Published outcomes following ligation of the intersphincteric fistula tract (LIFT) for high transsphincteric fistulas (HTFs) are equivocal probably because most trials are small and comprise ...mixed patient populations. The aim of this study was to highlight the long‐term efficacy of LIFT for HTFs in a large homogeneous sample and to determine the risk factors that contribute to non‐healing resulting in failure and recurrence.
Method
A retrospective study was performed which assessed patients with HTFs treated by LIFT without prior loose setons from September 2012 to December 2017. Continence function was evaluated by the Wexner incontinence scale and anal manometry. Quality of life was assessed by using the faecal incontinence quality of life (FIQL) scale with four domains: lifestyle, coping, depression and embarrassment.
Results
Seventy patients with HTFs underwent 71 LIFT procedures. The primary healing rate was 81.7% with a median follow‐up duration of 16.5 (range 4.5–68) months. The healing rates of mature and immature fistulas were 83.7% and 77.3%, respectively. Two patients suffered failure with an unhealed intersphincteric wound. Recurrence occurred in 11 patients. Incontinence of flatus, present in four patients before surgery, improved postoperatively. Two patients undergoing LIFT combined with fistulotomy complained of flatus incontinence after surgery. No significant differences between preoperative and postoperative Wexner score, maximum resting pressure and maximum squeeze pressure were detected. The FIQL was improved in lifestyle, coping and depression. No risk factor for non‐healing was found.
Conclusion
LIFT has a promising long‐term outcome for HTFs, with negligible impairment on continence and improved quality of life.
Due to the drive for better environmental protection and energy conversion efficiency, on-site generation of CO
x
-free hydrogen from ammonia decomposition for fuel cell applications has attracted ...much attention. The development of high performance solid catalysts is essential for the supply of such hydrogen from ammonia. In this mini-review, we provide a summary of the reaction kinetics of catalytic ammonia decomposition. Comparisons are then made among the catalysts that have different active components, supports, and promoters. According to the works reported in the literature and our recent research results, Ru is the most active catalyst, carbon nanotubes (CNTs) are the most effective support, and KOH is the best promoter. An increase in Ru dispersion results in better catalytic performance. Both support basicity and conductivity are important criteria for a NH
3 decomposition catalyst of high efficiency; and it seems possible to generate novel advanced support, such as oxide-CNTs nanocomposite materials, that bears such characteristics. Also, proper removal of the electron-withdrawing entities that originate from the precursors of active component, support or promoter can be effective in enhancing the catalytic activity of a Ru catalyst.
In this study, aluminum matrix composites reinforced with micro-TiN were fabricated using selective laser melting (SLM) technique. The study investigates the effects of TiN content on densification, ...microstructure evolution, crystal textures, and mechanical properties. The results show that the relative density of composite samples containing 0?3 wt. % TiN exceeds 98%. However, further increase in TiN content leads to a decrease in relative density. The TiN particles are uniformly distributed and wetted by the AlSi10Mg matrix, forming a graded interfacial layer. The TiN particles refine the matrix grains and significantly reduce the prevalence (001) texture by promoting a heterogeneous nucleation process. In comparison to the AlSi10Mg alloy, the TiN/AlSi10Mg composite exhibits improved microhardness, tensile strength, and wear resistance. The exceptional mechanical properties of the Al matrix composites are attributed to the dispersion strengthening of the TiN particles and the fine-grain strengthening of the matrix. The optimal TiN content is found to be 3 wt. %, resulting in excellent mechanical performance of the fabricated samples (132.4?4.1 HV for hardness and 379.7?4.6 MPa for tensile strength) with a low friction coefficient of 0.49.
Aims To investigate the relationships between a known history of diabetes and ambient fasting plasma glucose (FPG) levels with death and morbidity rates in patients with severe acute respiratory ...syndrome (SARS).
Methods In this retrospective analysis, the clinical and biochemical characteristics of 135 patients who had died from SARS, 385 survivors of SARS and 19 patients with non‐SARS pneumonia were compared.
Results All patients were treated according to a predefined protocol. Before steroid treatment, the mean FPG level was significantly higher in the SARS group (deceased vs. survivors vs. non‐SARS pneumonia group: 9.7 ± 5.2 vs. 6.5 ± 3.0 vs. 5.1 ± 1.0 mmol/l, P < 0.01). In the SARS group, the percentage of patients with a known history of diabetes was significantly higher in the deceased patients than in the survivors (21.5% vs. 3.9%, P < 0.01). Among patients with no known history of diabetes and before commencement of steroid therapy, those who had hypoxaemia (SaO2 < 93%) had higher FPG levels than those who did not have hypoxia in both the survivor (8.7 ± 4.9 vs. 6.3 ± 2.1 mmol/l, P < 0.001) and deceased (9.8 ± 4.8 vs. 7.2 ± 1.5 mmol/l, P < 0.001) groups. A known history of diabetes odds ratio (OR) 3.0, 95% confidence interval (CI) 1.4, 6.3; P = 0.005 and FPG ≥ 7.0 mmol/l before steroid treatment (OR 3.3, 95% CI 1.4, 7.7, P = 0.006) were independent predictors of death. During the course of the illness, FPG levels were negatively associated with SaO2 (β =−0.682 ± 0.305, P = 0.025, general estimation equation model) in SARS patients. Survival analysis showed that FPG was independently associated with an increased hazard ratio (HR) of mortality (HR = 1.1, 95% CI 1.0, 1.1, P = 0.001) and hypoxia (HR = 1.1, 95% CI 1.0, 1.1, P = 0.002) after controlling for age and gender.
Conclusions A known history of diabetes and ambient hyperglycaemia were independent predictors for death and morbidity in SARS patients. Metabolic control may improve the prognosis of SARS patients.
The epithelial-mesenchymal transition (EMT) induced by chemotherapeutic agents promotes malignant tumor progression; however, the mechanism underlying the drug-induced EMT remains unclear. In this ...study, we reported that miR-448 is the most downregulated microRNA following chemotherapy. Suppression of miR-448 correlated with EMT induction in breast cancer in vitro and in vivo. With the use of chromatin immunoprecipitation-seq analysis, we demonstrated that miR-448 suppression induces EMT by directly targeting special AT-rich sequence-binding protein-1 (SATB1) mRNA, leading to elevated levels of amphiregulin and thereby, increasing epidermal growth factor receptor (EGFR)-mediated Twist1 expression, as well as nuclear factor κB (NF-κB) activation. On the other hand, we also found that the adriamycin-activated NF-κB directly binds the promoter of miR-448 suppressing its transcription, suggesting a positive feedback loop between NF-κB and miR-448. Furthermore, all patients who received cyclophosphamide (CP), epirubicin plus taxotere/CP, epirubicin plus 5-fluorouracil chemotherapy showed miR-448 suppression, an increased SATB1, Twist1 expression and acquisition of mesenchymal phenotypes. These findings reveal an underlying regulatory pathway, in which the autoregulation between NF-κB and miR-448 is important for restrain miR-448 suppression upon chemotherapy and may have a role in the regulation of chemotherapy-induced EMT. Disruption of the NF-κB-miR-448 feedback loop during clinical treatment may improve the chemotherapy response of human breast cancers in which EMT is a critical component.
We report a study of the processes of e^{+}e^{-}→K^{+}D_{s}^{-}D^{*0} and K^{+}D_{s}^{*-}D^{0} based on e^{+}e^{-} annihilation samples collected with the BESIII detector operating at BEPCII at five ...center-of-mass energies ranging from 4.628 to 4.698 GeV with a total integrated luminosity of 3.7 fb^{-1}. An excess of events over the known contributions of the conventional charmed mesons is observed near the D_{s}^{-}D^{*0} and D_{s}^{*-}D^{0} mass thresholds in the K^{+} recoil-mass spectrum for events collected at sqrts=4.681 GeV. The structure matches a mass-dependent-width Breit-Wigner line shape, whose pole mass and width are determined as (3982.5_{-2.6}^{+1.8}±2.1) MeV/c^{2} and (12.8_{-4.4}^{+5.3}±3.0) MeV, respectively. The first uncertainties are statistical and the second are systematic. The significance of the resonance hypothesis is estimated to be 5.3 σ over the contributions only from the conventional charmed mesons. This is the first candidate for a charged hidden-charm tetraquark with strangeness, decaying into D_{s}^{-}D^{*0} and D_{s}^{*-}D^{0}. However, the properties of the excess need further exploration with more statistics.
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