Background and Aim
Remimazolam tosilate (RT) is a new short‐acting GABA(A) receptor agonist, having potential to be an effective option for procedural sedation. Here, we aimed to compare the efficacy ...and safety of RT with propofol in patients undergoing upper gastrointestinal endoscopy.
Methods
This positive‐controlled, non‐inferiority, phase III trial recruited patients at 17 centers, between September 2017 and November 2017. A total of 384 patients scheduled to undergo upper gastrointestinal endoscopy were randomly assigned to receive RT or propofol. Primary endpoint was the success rate of sedation. Adverse events (AEs) were recorded to evaluate safety.
Results
The success rate of sedation in the RT group was non‐inferior to that in the propofol group (97.34% vs 100.00%; difference in rate −2.66%, 95% CI −4.96 to −0.36, meeting criteria for non‐inferiority). Patients in the RT group had longer time to adequate sedation (P < 0.0001) but shorter time to fully alert (P < 0.0001) than that in the propofol group. The incidences of hypotension (13.04% vs 42.86%, P < 0.0001), treatment‐related hypotension (0.54% vs 5.82%, P < 0.0001), and respiratory depression (1.09% vs 6.88%, P = 0.0064) were significantly lower in the RT group. AEs were reported in 74 (39.15%) patients in the RT group and 114 (60.32%) patients in the propofol group, with significant difference (P < 0.0001).
Conclusion
This trial established non‐inferior sedation success rate of RT compared with propofol. RT allows faster recovery from sedation compared with propofol. The safety profile is favorable and appears to be superior to propofol, indicating that it was feasible and well tolerated for patients.
A pathology‐adaptive nanosystem, in which nest‐like hosts are built based on nanofibers that are transformed from i.v. injected nanoparticles under the acidic tumor microenvironment. The solid tumor ...is artificially modified by nest‐like hosts readily and firmly, resulting in highly efficient accumulation and stabilization of guest theranostics. This strategy shows great potential for the theranostics delivery to tumors.
Smart regulation of substance permeability through porous membranes is highly desirable for membrane applications. Inspired by the stomatal closure feature of plant leaves at relatively high ...temperature, here we report a nano-gating membrane with a negative temperature-response coefficient that is capable of tunable water gating and precise small molecule separation. The membrane is composed of poly(N-isopropylacrylamide) covalently bound to graphene oxide via free-radical polymerization. By virtue of the temperature tunable lamellar spaces of the graphene oxide nanosheets, the water permeance of the membrane could be reversibly regulated with a high gating ratio. Moreover, the space tunability endows the membrane with the capability of gradually separating multiple molecules of different sizes. This nano-gating membrane expands the scope of temperature-responsive membranes and has great potential applications in smart gating systems and molecular separation.
To profile gut microbiome-associated metabolites in serum and investigate whether these metabolites could distinguish individuals with colorectal cancer (CRC) or adenoma from normal healthy ...individuals.
Integrated analysis of untargeted serum metabolomics by liquid chromatography-mass spectrometry and metagenome sequencing of paired faecal samples was applied to identify gut microbiome-associated metabolites with significantly altered abundance in patients with CRC and adenoma. The ability of these metabolites to discriminate between CRC and colorectal adenoma was tested by targeted metabolomic analysis. A model based on gut microbiome-associated metabolites was established and evaluated in an independent validation cohort.
In total, 885 serum metabolites were significantly altered in both CRC and adenoma, including eight gut microbiome-associated serum metabolites (GMSM panel) that were reproducibly detected by both targeted and untargeted metabolomics analysis and accurately discriminated CRC and adenoma from normal samples. A GMSM panel-based model to predict CRC and colorectal adenoma yielded an area under the curve (AUC) of 0.98 (95% CI 0.94 to 1.00) in the modelling cohort and an AUC of 0.92 (83.5% sensitivity, 84.9% specificity) in the validation cohort. The GMSM model was significantly superior to the clinical marker carcinoembryonic antigen among samples within the validation cohort (AUC 0.92 vs 0.72) and also showed promising diagnostic accuracy for adenomas (AUC=0.84) and early-stage CRC (AUC=0.93).
Gut microbiome reprogramming in patients with CRC is associated with alterations of the serum metabolome, and GMSMs have potential applications for CRC and adenoma detection.
Metallothioneins (MTs) is a metal ion binding protein to detoxify heavy metal stress in plant cells. This study examines involvement of MTs in metal chelation and ROS scavenging in rice seedling ...under Cr induction either Cr(VI) or Cr(III) at three different effective concentrations using Agilent 44K rice microarray and real-time PCR technology. Results showed that the concentration of Cr was higher in roots than in shoots in both Cr treatments. Accumulation of both H2O2 and O2− in rice tissues was evident, but the fluctuation of H2O2 was more remarkable than O2−. Both Cr exposures resulted in enhancement of MTs in plant tissues. Results from PCR analysis confirmed that ten specific OsMT genes responsible for regulating ROS removal were expressed differentially in plant tissues as well as in Cr variants, suggesting that their different regulation and responsiveness strategies. Expression patterns of metal chelation-related OsMT genes, after Cr exposure were also inconsistent in rice tissues. Longer exposure periods caused more transcriptional changes in both Cr treatments. We also noticed that OsMT1b might carry more weight during Cr chelation in roots rather than in shoots, while OsMT2c had more important role in eliminating H2O2 accumulation in shoots than roots. These results suggest that different speciation of Cr in rice tissues resulted in inconsistent transcriptional changes of OsMT genes, which functioned in different regulation and responsiveness pathways responsible for metal ions chelating and ROS scavenging during Cr detoxification.
•The concentration of Cr was higher in roots than in shoots in both Cr treatments.•The fluctuation of H2O2 was more remarkable than O2− in rice tissues under both Cr exposures.•Both Cr exposures resulted in enhancement of MTs in rice tissues.•OsMT genes responsible for regulating ROS removal were expressed differentially in plant tissues as well as in Cr variants.•Expression patterns of metal chelation-related OsMT genes after Cr exposure were also inconsistent.
Probabilistic power flow (PPF) plays a critical role in power system analysis. However, the high computational burden makes it challenging for the practical implementation of PPF. This paper proposes ...a model-based deep learning approach to overcome the computational challenge. A deep neural network (DNN) is used to approximate the power flow calculation and is trained according to the physical power flow equations to improve its learning ability. The training process consists of several steps: 1) the branch flows are added into the objective function of the DNN as a penalty term, which improves the approximation accuracy of the DNN; 2) the gradients used in the back propagation process are simplified according to the physical characteristics of the transmission grid, which accelerates the training speed while maintaining effective guidance of the physical model; and 3) an improved initialization method for the DNN parameters is proposed to improve the convergence speed. The simulation results demonstrate the accuracy and efficiency of the proposed method in standard IEEE and utility benchmark systems.
This study highlights the roles of different N sources (N starvation −N, nitrate +NO3 –, and ammonium +NH4 +) in specific amino acids involved in rice proline (Pro) metabolism under hexavalent ...chromium Cr(VI) stress. In treatment with Cr(VI) – N, the content of glutamate (Glu) in shoots was comparable to that of Pro, while the content of Glu in the roots was significantly higher than that of Pro. In case of treatment with Cr(VI) + NO3 –/NH4 +, the content of Glu in both tissues was significantly higher than that of Pro, suggesting that the synthesis of γ-aminobutyric acid and glutathione was most likely involved. Pro synthesis in rice is mainly derived from the Glu pathway rather than the ornithine (Orn) pathway, which is strongly affected by different N sources. The genetic regulation network of Pro metabolism demonstrated a good signal for describing amino acid balance in rice under Cr(VI) stress.
Abstract
Background
Sex and reproductive status differences exist in both non-alcoholic fatty liver disease (NAFLD) and body composition. Our purpose was to investigate the relationship between body ...composition and the severity of liver steatosis and fibrosis in NAFLD in different sex and reproductive status populations.
Methods
This cross-sectional study included 880 patients (355 men, 417 pre-menopausal women, 108 post-menopausal women). Liver steatosis and fibrosis and body composition data were measured using FibroScan and a bioelectrical impedance body composition analyzer (BIA), respectively, and the following parameters were obtained: liver stiffness measurement (LSM), controlled attenuation parameter (CAP), waist circumference (WC), body mass index (BMI), percent body fat (PBF), visceral fat area (VFA), appendicular skeletal muscle mass (ASM), appendicular skeletal muscle mass index (ASMI), fat mass (FM), fat free mass (FFM), and FFM to FM ratio (FFM/FM). Multiple ordinal logistic regression (MOLR) was used to analyze the independent correlation between body composition indicators and liver steatosis grade and fibrosis stage in different sex and menopausal status populations.
Results
Men had higher WC, ASM, ASMI, FFM, and FFM/FM than pre- or post-menopausal women, while pre-menopausal women had higher PBF, VFA, and FM than the other two groups (p < 0.001). Besides, men had greater CAP and LSM values (p < 0.001). For MOLR, after adjusting for confounding factors, WC (OR, 1.07; 95% CI, 1.02–1.12; P = 0.011) and FFM/FM (OR, 0.52; 95% CI, 0.31–0.89; P = 0.017) in men and visceral obesity (OR, 4.16; 95% CI, 1.09–15.90; P = 0.037) in post-menopausal women were independently associated with liver steatosis grade. WC and visceral obesity were independently associated with liver fibrosis stage in men (OR, 1.05; 95% CI, 1.01–1.09, P = 0.013; OR, 3.92; 95% CI, 1.97–7.81; P < 0.001, respectively).
Conclusions
Increased WC and low FFM/FM in men and visceral obesity in post-menopausal women were independent correlates of more severe liver steatosis. In addition, increased WC and visceral obesity were independent correlates of worse liver fibrosis in men. These data support the sex- and reproductive status-specific management of NAFLD.
Toxic metal-induced overaccumulation of anthocyanin (ATH) in plants can oxidize proteins and break DNA. Herein, the role of exogenous proline (Pro) on the repression of ATH accumulation in rice ...seedlings during hexavalent chromium Cr(VI) exposure was studied. Results indicated that exogenous Pro-mediated regulation of jasmonate signals activated the MYB-bHLH-WDR complex to repress ATH accumulation in rice tissues under Cr(VI) stress. Biochemical and transcript analysis indicated that exogenous Pro promoted the synthesis of jasmonic acid (JA) and its molecularly active metabolite jasmonic acid isoleucine (JA-Ile) in rice tissues under Cr(VI) stress. Increment in the endogenous level of jasmonates positively triggered the expression of genes responsible for the JA signaling pathway and activated the MYB-bHLH-WDR complex, eventually repressing the glycosylation of anthocyanidin to form ATH in rice tissues. In conclusion, exogenous proline-mediated regulation on jasmonate signals was tissue-specific under Cr(VI) stress and a more positive effect was detected in shoots rather than roots.
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