The tumor suppressor gene
is frequently mutated or inactivated in bladder cancer (BLCA), which is implicated in the pathogenesis of tumor. However, the cellular mechanisms of
mutations are ...complicated, yet well-defined, but their clinical prognostic value in the management of BLCA remains controversial. This study aimed to explore the role of
mutation in regulating the tumor microenvironment (TME), elucidate the effects of
activity on BLCA prognosis and immunotherapy response.
A
-related signature based on
-induced and
-repressed genes was used to construct a
activity-related score and classifier. The abundance of different immune cell types was determined using CIBERSORT to estimate immune cell infiltration. Moreover, the heterogeneity of the tumor immune microenvironment between the high and low
score groups was further evaluated using single-cell mass cytometry (CyTOF) and imaging mass cytometry (IMC). Moreover, pathway enrichment analysis was performed to explore the differential biological functions between tumor epithelial cells with high and low
activity scores. Finally, the receptor-ligand interactions between immune cells and tumor epithelial cells harboring distinct
activity were analyzed by single-cell RNA-sequencing.
The
activity-related gene signature differentiated well between
functional retention and inactivation in BLCA. BLCA patients with low
scores had worse survival prognosis, more
mutations, higher grade, and stronger lymph node metastasis than those with high
scores. Additionally, CyTOF and IMC analyses revealed that BLCA patients with low
scores exhibited a potent immunosuppressive TME. Consistently, single-cell sequencing results showed that tumor epithelial cells with low
scores were significantly associated with high cell proliferation and stemness abilities and strongly interacted with immunosuppressive receptor-ligand pairs.
BLCA patients with low
scores have a worse prognosis and a more immunosuppressive TME. This
activity-related signature can serve as a potential prognostic signature for predicting the immune response, which may facilitate the development of new strategies for immunotherapy in BLCA.
Friction stir welding (FSW) is a new solid-state joining process for joining light metals, such as magnesium (Mg) alloys. However, the texture-induced softening mechanism (in stir zone, SZ) tends to ...cause the worsening of mechanical properties in FSW Mg alloys. In this work, multi-pass hot-rolling and subsequent annealing is used to ameliorate the FSW AZ31 alloy plate. The results show that multi-pass hot-rolling leads to the c-axes of most grains in the SZ approximately perpendicular to the normal direction (ND) transforming into these almost parallel to the ND, accompanied with multiple twin types. After subsequent annealing, twins, as nucleation sites, promote the formation of new grains with off-basal texture, resulting in the weak basal texture. Compared with the FSW plate and the initial plate, the rolled-annealed FSW plate exhibits a relatively uniform hardness distribution and a “strength-ductility” synergy, which are mainly attributed to an appropriate texture feature and a homogeneous grain structure. This work provides a new idea for the development of new high-performance FSW Mg alloys.
Dithiocarbamates synthesis is extremely important in plenty of biomedical and agrochemical applications, especially fungicide development, but remains a great challenge. In this work, we have ...successfully developed a multicomponent reaction protocol to convert H2S into S-alkyl dithiocarbamates under constant current conditions. No additional oxidants nor additional catalysts are required, and due to mild conditions, the reactions display a broad substrate scope, including varieties of thiols or disulfides.
Arterial stiffness, glycemic control and blood pressure are risk factors of macrovascular complications in type 2 diabetes. This study aimed to investigate the combined association of arterial ...stiffness, glycemic control and hypertension status with the occurrence of diabetic macrovascular complication.
A total of 1870 patients of diabetes were enrolled from Beijing Health Management Cohort between 2008 and 2018 as baseline, and then followed for macrovascular complication onset. We proposed a composite risk score (0-4) by arterial stiffness severity, pool glycemic control and hypertension status. Cox model was used to estimate the hazard ratio (HR) and 95% confidence interval (CI).
The mean age (SD) of this population was 59.90 (12.29) years. During a median follow-up of 4.0 years, 359 (19.2%) patients developed macrovascular complication. Compared to the normal arterial stiffness and good glycemic control group, patients with severe arterial stiffness and pool glycemic control had the highest risk of macrovascular complications (HR: 2.73; 95% CI: 1.42-5.25). Similarly, those of severe arterial stiffness and hypertension had the highest risk (HR: 2.69; 95% CI: 1.61-4.50). Patients of the composite score > 2 had a significantly increased risk of macrovascular complication.
This study suggested the clinical importance of combined evaluation of arterial stiffness, glycemic control and hypertension status for the risk stratification and management of macrovascular complication of type 2 diabetes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Prior studies have reported the cross-sectional relationship between lung function and arterial stiffness, while the longitudinal association remains unclear to date. This study aimed to investigate ...whether abnormal lung function and its subtypes at baseline are associated with increased arterial stiffness using a cohort.
This was a secondary analysis extracting 2461 participants from Beijing Health Management Cohort as baseline and annually followed for development of arterial stiffness. Abnormal lung function was defined by forced expiratory volume in 1s <80% of the predicted value, forced vital capacity of the predicted value, or forced expiratory volume in 1s/forced vital capacity ratio <70%. Increased arterial stiffness was determined by brachial-ankle pulse wave velocity ≥1400 cm/s. Cox proportional hazards model was used to calculate the hazard ratio and population attributable fraction. The mean age was 42.8±8.1 years, and 444 (18.0%) cases developed increased arterial stiffness during a median follow-up of 3.0 years. The adjusted hazard ratio (95% CI) of arterial stiffness was 1.47 (95% CI, 1.10-1.96) for abnormal lung function, with a population attributable fraction of 3.9% (95% CI, 0.8-7.1). Of subtypes, only obstructive ventilatory dysfunction was significantly associated with arterial stiffness (adjusted hazard ratio, 2.06 95% CI, 1.27-3.36), not restricted ventilatory dysfunction (adjusted hazard ratio, 0.95 95% CI, 0.54-1.65). Consistent results were observed on multiple sensitivity analyses.
Our study indicated a longitudinal association of abnormal lung function with increased arterial stiffness using a large cohort, especially for the obstructive ventilatory dysfunction.
The Dimethyl ether (DME) kinetic model is significant to understand the DME combustion in the atmosphere containing high CO2 concentration, such as pressurized oxy-fuel combustion process and exhaust ...gas recirculation, and design the combustor. In this paper, the ignition delay times (IDTs) of DME were measured in a shock tube under the conditions of equivalence ratios of 0.5, 1 and 1.5, temperature ranges from 1007 K to 1340 K, and pressures of 2 and 11 atm. A detailed kinetic model of DME named as OXYDME was put forward based on the OXY-Aramco model, and was validated by the low and high temperature IDTs, laminar flame speeds, and species profiles measured in this work and those from literatures in atmospheres of O2/Ar/CO2, O2/N2, O2/N2/He/CO2 and O2/CO2. The OXYDME model was compared with OXY-Aramco, Liu-DME model in detail. The effects of CO2 on the DME ignition are very weak and not sensitive to the temperature and pressure. The reason for the weak effects of CO2 is that the chemical effects of CO2 promote ignition, which counteracts the inhibition effects caused by the physical properties of CO2. The chaperon effects of CO2 dominate the chemical effects. Meanwhile, the effects of the reactions with CO2 are very small.
Thermodynamic properties, electronic structures and spectroscopic properties of defects and Ce3+ in Y2O3 are studied by using the hybrid density functional theory associated with multi-reference ...configuration interaction ab-initio calculations. Thermodynamic transition energy levels of the easily generated oxygen vacancies in the host are analyzed according to HSE06-calculated formation energies, which may be conducive to interpretations of the persistent luminescence (PersL) of Y2O3-based phosphors. Besides, the locations of impurity states (caused by VO and Ce3+) in energy bands are obtained from derived density of states. Moreover, energies and oscillator strengths of 4f1 → 5d1−5 transitions of Ce3+ ions (at Y1 and Y2 sites) calculated from the CASSCF/CASPT2/RASSI−SO method agree reasonably well with experimental excitation spectra of Y2O3: Ce3+ phosphors, achieving the assignment of excitation spectra. The presented calculations can be applied to identify luminescent centers in Ce3+-doped phosphors and reveals possible native defects and their roles in the PersL of phosphors.
Display omitted
•Formation energies of intrinsic defects and Ce3+ ions in Y2O3 are calculated.•Thermodynamic transition energy levels of VO and Ce3+ in Y2O3 are obtained.•4f.→5d transitions of Ce3+ at Y1 and Y2 sites in Y2O3 are simulated.•Excitation bands in experimental spectra of Ce3+-doped Y2O3 are assigned.
Reactive oxygen species (ROS) are involved in the pathologic process of pulmonary arterial hypertension as either mediators or inducers. Rutin is a type of flavonoid which exhibits significant ...scavenging properties on oxygen radicals both in vitro and in vivo. In this study, we proposed that rutin attenuated hypoxia-induced pulmonary artery smooth muscle cell (PASMC) proliferation by scavenging ROS. Immunofluorescence data showed that rutin decreased the production of ROS, which was mainly generated through mitochondria and NADPH oxidase 4 (Nox4) in pulmonary artery endothelial cells (PAECs). Western blot results provided further evidence on rutin increasing expression of Nox4 and hypoxia-inducible factor-1α (HIF-1α). Moreover, cell cycle analysis by flow cytometry indicated that proliferation of PASMCs triggered by hypoxia was also repressed by rutin. However, N-acetyl-L-cysteine (NAC), a scavenger of ROS, abolished or diminished the capability of rutin in repressing hypoxia-induced cell proliferation. These data suggest that rutin shows a potential benefit against the development of hypoxic pulmonary arterial hypertension by inhibiting ROS, subsequently preventing hypoxia-induced PASMC proliferation.
In this work, trace amount of scandium element (Sc, 0.2 wt. %) was added to investigate microstructure and thermal stability evolution behavior of Sc-containing A356.2 alloy by using cyclic thermal ...exposure method. OM, SEM, TEM and image analysis software were applied to evaluate microstructure evolution. The results showed that both secondary dendrite arm spacing (SDAS) and average area of eutectic silicon increased with exposure temperature and exposure time increasing. In addition, thermal stabilities of ultimate tensile strength (UTS), yield strength (YS), elongation (EI) and micro-hardness were sensitive to cyclic thermal exposure temperatures. E.g., under 200°C exposure temperature, more than 6 cycles were needed for the mechanical properties getting stable, and with exposure temperature of 250°C about 4 cycles were needed. While, for exposure temperatures of 300°C and 350°C, only 2 cycles were needed. Precipitation mechanisms of Nano Si (syn) phase and Al3Sc phase inside of grains were discussed, and comprehensive effect of Al3Sc, Nano Si (syn) phase, SDAS and eutectic silicon was responsible for the thermal stability of the alloy under cyclic thermal exposure conditions.
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