These findings indicate that applying single atoms would be a promising strategy for designing biofouling-resistant adsorbents for uranium extraction from seawater.Smad4, a key mediator of the transforming growth factor-β signaling, is mutated or deleted in 20% of pancreatic ductal adenocarcinoma (PDAC) cancers and significantly affects cancer development. However, the effect of Smad4 loss on the immunogenicity and tumor immune microenvironment of PDAC is still unclear. Here, a surprising function of Smad4 in suppressing mouse PDAC tumor immunogenicity is identified. Although Smad4 deletion in tumor cells enhances proliferation in vitro, the in vivo growth of Smad4-deficient PDAC tumor is significantly inhibited on immunocompetent C57BL/6 (B6) mice, but not on immunodeficient mice or CD8+ cell-depleted B6 mice. Mechanistically, Smad4 deficiency significantly increases tumor cell immunogenicity by promoting spontaneous DNA damage and stimulating STING-mediated type I interferon signaling,which contributes to the activation of type 1 conventional dendritic cells (cDC1) and subsequent CD8+ T cells for tumor control. Furthermore, retarded tumor growth of Smad4-deficient PDAC cells on B6 mice is largely reversed when Sting is codeleted, or when the cells are implanted into interferon-alpha receptor-deficientmice or cDC1-deficientmice. Accordingly, Smad4 deficiency promotes PDAC immunogenicity by inducing tumor-intrinsic DNA damage-elicited type I interferon signaling.
The angiotensin receptor-neprilysin inhibitor (ARNI), sacubitril/valsartan, has been shown to be effective in treatment of patients with heart failure (HF), but limited data are available in patients with advanced disease. This retrospective observational study assessed the effects of ARNI treatment in patients with advanced HF.
We reviewed medical records of all advanced HF patients evaluated at our centre for unconventional therapies from September 2016 to January 2019. We studied 44 patients who started ARNI therapy and who had a haemodynamic assessment before beginning ARNI and after 6±2months. The primary endpoint was variation in pulmonary pressures and filling pressures at 6months after starting ARNI therapy. Mean patient age was 51.6±7.4years; 84% were male. At 6±2months after starting ARNI, there was significant reduction of systolic pulmonary artery pressure [32mmHg, interquartile range (IQR) 27-45 vs. 25mmHg, IQR 22.3-36.5; P<0.0001] and mean pulmonary artery pressure (20mmHg, IQR 15.3-29.8 vs. 17mmHg, IQR 13-24.8; P=0.046). Five of 22 patients (23%) were deferred from the heart transplant list because of improvement, whereas four were listed de novo. After 23±9months, three patients were treated with a left ventricular assist device implantation, whereas six patients underwent heart transplantation (one in emergency conditions for refractory ventricular tachycardia).
Sacubitril/valsartan is effective in reducing filling pressures and pulmonary pressures in patients with advanced HF. The absence of adverse events during follow-up suggests that sacubitril/valsartan is safe and well-tolerated in this cohort of patients.
Sacubitril/valsartan is effective in reducing filling pressures and pulmonary pressures in patients with advanced HF. The absence of adverse events during follow-up suggests that sacubitril/valsartan is safe and well-tolerated in this cohort of patients.Aqueous supercapacitors have the superiorities of high safety, environmental friendliness, inexpensive, etc. High energy density supercapacitors are not conducive to manufacturing due to the limitation of water thermodynamic decomposition potential, resulting in a narrow working voltage window. To address such challenges, a great endeavor has started to investigate high voltage aqueous supercapacitors as well as making some progress. This review summarizes key strategies regarding the realization of wide working voltage of aqueous supercapacitors and analyzes the involved mechanism, including the optimization of electrodes, electrolytes, diaphragms, and supercapacitor structures. From the perspective of extending the theoretical voltage window, electrode functionalization, heteroatom doping, neutral electrolyte, water-in-salt electrolyte, introducing redox mediators into electrolyte, and designing asymmetric structure are effective strategies for achieving this goal. Further, the actual voltage window can be maximized by optimizing the electrode mass ratio, adjusting potential of zero voltage, and electrode functionalization. The challenge and future of expanding working voltage of aqueous supercapacitors are further discussed. Importantly, this review provides inspiration for the development of supercapacitors with high energy density.Numerous studies have explored new materials for electrocatalysts, but it is difficult to discover materials that surpass the catalytic activity of current commercially available noble metal electrocatalysts. In contrast to conventional transition metal alloys, high-entropy alloys (HEAs) have immense potential to maximize their catalytic properties because of their high stability and compositional diversity as oxygen evolution reactions (OERs). This work presents medium-entropy alloys (MEAs) as OER electrocatalysts to simultaneously satisfy the requirement of high catalytic activity and long-term stability. The surface of MEA electrocatalyst is tailored to suit the OER via anodizing and cyclic voltammetry activation methods. Optimized electrical properties and hydrophilicity of the surface enable an extremely low overpotential of 187 mV for achieving the current density of 10 mA cm-2 alkaline media. Furthermore, a combined photovoltaic-electrochemical system with MEA electrocatalyst and a perovskite/Si tandem solar cell exhibits a solar-to-hydrogen conversion efficiency of 20.6% for an unassisted hydrogen generation system. These results present a new pathway for designing sustainable high efficiency water splitting cells.The construction of ideal tissue engineering trachea has always been a difficult problem in trachea transplantation surgery. The biological characteristics of decellularized matrix prepared by detergent-enzymatic (DEM) and 3D printing biomimetic scaffold (PTS) in vivo and in vitro were compared. In order to comprehensively evaluate its performance, we tested morphological and biomechanical characteristics of the native tracheas(Group A), DEM(Group B), and PTS(Group C). The above groups were co-cultured with bone marrow mesenchymal stem cells (BMSCs), after which cell attachment and proliferation on the scaffolds were detected. Allogeneic implantation experiments were performed to assess the in vivo biocompatibility of the studied scaffolds. Moreover, an in-situ experiment of the tracheal repair was conducted to compare the survival of every group. The biomechanical properties of PTS were significantly better than those of other scaffolds (P less then .05). And they retained their structural integrity in the host compared with the other scaffolds (P less then .05). Besides, significantly milder immune-rejection reactions were observed in Group C than those in Group A (P less then .05). In situ experiments showed that Group C significantly a good postoperative condition compared with the other scaffold groups (P less then .05). Fiberoptic bronchoscopy analysis of PTS showed a better condition in the lumen. In conclusion, PTS has excellent biomechanical properties. Although the PTS group showed lower biocompatibility than the decellularized group, it exhibited better cell attachment and proliferation. In situ transplantation results showed that PTS could be an ideal source of tissue engineering material for tracheal repair.Abnormally expressed long non-coding RNAs (lncRNAs) have been recognized as potential diagnostic biomarkers or therapeutic targets in non-small cell lung cancer (NSCLC). The role of the novel lnc-CYB561-5 in NSCLC and its specific biological activity remain unknown. In this study, lncRNAs highly expressed in NSCLC tissue samples compared with paired adjacent normal tissue samples and atypical adenomatous hyperplasia were identified by RNA-seq analysis. Lnc-CYB561-5 is highly expressed in human NSCLC and is associated with a poor prognosis in lung adenocarcinoma. In vivo, downregulation of lnc-CYB561-5 significantly decreases tumour growth and metastasis. In vitro, lnc-CYB561-5 knockdown treatment inhibits cell migration, invasion and proliferation ability, as well as glycolysis rates. In addition, RNA pulldown and RNA immunoprecipitation (RIP) assays show that basigin (Bsg) protein interacts with lnc-CYB561-5. Overall, this study demonstrates that lnc-CYB561-5 is an oncogene in NSCLC, which is involved in the regulation of cell proliferation and metastasis. Lnc-CYB561-5 interacts with Bsg to promote the expression of Hk2 and Pfk1 and further lead to metabolic reprogramming of NSCLC cells.
To assess the diagnostic accuracy of temporal artery ultrasound compared with temporal artery biopsy and clinical diagnosis in patients with suspected giant cell arteritis (GCA) over 10years in an Australian center.
Patients presenting to Westmead Hospital with possible GCA from March 2011 to December 2020 were retrospectively identified. The following parameters were obtained from the medical record clinical presentation, inflammatory markers, temporal artery ultrasound findings, and temporal artery biopsy report. Data were assembled in a 2×2 table; sensitivity and specificity of temporal artery ultrasound compared with temporal artery biopsy and clinical diagnosis were calculated.
Over the 10-year study period, 65 temporal artery ultrasounds were performed in 63 patients (n=65; 61.9% female) with a mean±standard deviation age of 69.6±12.3years. Thirteen out of 65 (20%) temporal artery ultrasounds had findings suggestive of GCA. Twenty patients (31.7%) had a clinical diagnosis of GCA irrespective of sonographic or biopsy findings. Compared with temporal artery biopsy, temporal artery ultrasound had a sensitivity of 71.4% and specificity of 93.3%. Compared with clinical diagnosis made by the treating rheumatologist, temporal artery ultrasound had a sensitivity of 55% and specificity of 95.3%.
Temporal artery ultrasound is a useful non-invasive investigation in the assessment of suspected GCA. If positive in the setting of a suggestive clinical presentation, a temporal artery ultrasound probably avoids the need for a temporal artery biopsy. Temporal artery ultrasound could be more widely used in the clinical management of GCA.
Temporal artery ultrasound is a useful non-invasive investigation in the assessment of suspected GCA. If positive in the setting of a suggestive clinical presentation, a temporal artery ultrasound probably avoids the need for a temporal artery biopsy. Temporal artery ultrasound could be more widely used in the clinical management of GCA.
The Leksell Gamma Knife Icon unit (IU) was introduced recently as an upgrade to the Perfexion unit (PU) at our Gamma Knife practice. In the current study, we sought mainly to characterize dosimetry and targeting accuracy of the IU treatment deliveries using both invasive frame and frameless treatment workflows.
Relative output factors were measured by delivering single-shot 4, 8 and 16mm radiation profiles in the manufacturer's acrylonitrile butadiene styrene spherical phantom in coronal and sagittal planes using EBT3 film. Resultant dosimetry was compared with the manufacturer's dose calculation and derived output factors were compared with the manufacturer's published value. selleck chemicals Geometric consistency of stereotactic coordinates based on cone-beam computed tomography (CBCT) versus the traditional conventional CT-based method was characterized using a rigid phantom containing nine fiducial indicators over four separate trials. End-to-end (E2E) testing using EBT3 film was designed to evaluate both dosimetric and geometric accuracy for hypothetical framed and frameless workflows.selleck chemicals
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