The difference in mean arterial pressure induced by remimazolam compared to etomidate in the presence of fentanyl at tracheal intubation: A randomized controlled trial

Background: Combined use of hypnotic and opioids during anesthesia inductions decreases blood pressure. Post-induction hypotension (PIHO) is the most common side effect of anesthesia induction. We aimed to compare the difference in mean arterial pressure (MAP) induced by remimazolam with that induced by etomidate in the presence of fentanyl at tracheal intubation.Methods: We assessed 138 adult patients with American Society of Anesthesiologists physical status I–II who underwent elective urological surgery. Patients were randomly allocated to receive either remimazolam or etomidate as alterative hypnotic in the presence of fentanyl during anesthesia induction. Comparable BIS values were achieved in both groups. The primary outcome was the difference in the MAP at tracheal intubation. The secondary outcomes included the characteristics of anesthesia, surgery, and adverse effects.Results: The MAP was higher in the etomidate group than in the remimazolam group at tracheal intubation (108 [22] mmHg vs. 83 [16] mmHg; mean difference, −26; 95% confidence interval [CI], −33 to −19; p < 0.0001). Heart rate was significantly higher in the etomidate group than in the remimazolam group at tracheal intubation. The patients’ condition warranted the administration of ephedrine more frequently in the remimazolam group (22%) than in the etomidate group (5%) (p = 0.0042) during anesthesia induction. The remimazolam group had a lower incidence of hypertension (0% vs. 9%, p = 0.0133), myoclonus (0% vs. 47%, p < 0.001), and tachycardia (16% vs. 35%, p = 0.0148), and a higher incidence of PIHO (42% vs. 5%, p = 0.001) than the etomidate group during anesthesia induction.Conclusion: Remimazolam was associated with lower MAP and lower heart rate compared to etomidate in the presence of fentanyl at tracheal intubation. Patients in the remimazolam group had a higher incidence of PIHO, and their condition warranted the administration of ephedrine more frequently than in the etomidate group during anesthesia induction

Application of Backpropagation-Artificial Neural Network in Quality Prediction of Irradiated Black Pepper Beef

To investigate the effects of different irradiation treatments on the quality of black pepper beef during storage, a backpropagation-artificial neural network (BP-ANN) model for predicting various quality attributes of black pepper beef was developed based on physicochemical indicators. Irradiation at a dose of 3–4 kGy effectively delayed the loss of juice, lipid oxidation, and protein degradation in black pepper beef during storage, maintained its hardness and microstructure, and increased the contents of umami (Asp) and sweet (Gly, Ala and Ser) amino acids. The BP-ANN model was optimized with the juice loss, thiobarbituric acid reactive substances (TBARs) value, total volatile basic nitrogen (TVB-N) content, tropomyosin band intensity ratio, myosin heavy chain band intensity ratio, and total free amino acid content of irradiated black pepper beef as input variables. The ReLU function was used as the activation function, with 14 neurons in the hidden layer and 100 iterations. The results showed that the 6-14-6 BP-ANN model could predict the quality changes of irradiated black pepper beef well, and have great potential in predicting various qualities of irradiated meat products

Clonal evolution in liver cancer at single-cell and single-variant resolution.

Genetic heterogeneity of tumor is closely related to its clonal evolution, phenotypic diversity and treatment resistance, and such heterogeneity has only been characterized at single-cell sub-chromosomal scale in liver cancer. Here we reconstructed the single-variant resolution clonal evolution in human liver cancer based on single-cell mutational profiles. The results indicated that key genetic events occurred early during tumorigenesis, and an early metastasis followed by independent evolution was observed in primary liver tumor and intrahepatic metastatic portal vein tumor thrombus. By parallel single-cell RNA-Seq, the transcriptomic phenotype of HCC was found to be related with genetic heterogeneity. For the first time we reconstructed the single-cell and single-variant clonal evolution in human liver cancer, and dissection of both genetic and phenotypic heterogeneity will facilitate better understanding of their relationship

Multiple Kinases Involved in the Nicotinic Modulation of Gamma Oscillations in the Rat Hippocampal CA3 Area

Neuronal synchronization at gamma band frequency (20–80 Hz, γ oscillations) is closely associated with higher brain function, such as learning, memory and attention. Nicotinic acetylcholine receptors (nAChRs) are highly expressed in the hippocampus, and modulate hippocampal γ oscillations, but the intracellular mechanism underlying such modulation remains elusive. We explored multiple kinases by which nicotine can modulate γ oscillations induced by kainate in rat hippocampal area CA3 in vitro. We found that inhibitors of cyclic AMP dependent kinase (protein kinase A, PKA), protein kinase C (PKC), N-methyl-D-aspartate receptor (NMDA) receptors, Phosphoinositide 3-kinase (PI3K) and extracellular signal-related kinases (ERK), each individually could prevent the γ oscillation-enhancing effect of 1 μM nicotine, whereas none of them affected baseline γ oscillation strength. Inhibition of the serine/threonine kinase Akt increased baseline γ oscillations and partially blocked its nicotinic enhancement. We propose that the PKA-NMDAR-PI3K-ERK pathway modifies cellular properties required for the nicotinic enhancement of γ oscillations, dependent on a PKC-ERK mediated pathway. These signaling pathways provide clues for restoring γ oscillations in pathological conditions affecting cognition. The suppression of γ oscillations at 100 μM nicotine was only dependent on PKA-NMDAR activation and may be due to very high intracellular calcium levels

Transfer of an Aluminium Atom: An Avenue to Aluminium Heterocycles

Synthetic chemistry targets building up molecular complexity using simple substrates through simple processes. We disclose an unprecedented Al-atom transfer strategy for the synthesis of aluminium heterocycles with high atom economy. This strategy involves an effective cycloaddition of a free carbazolyl-aluminylene with unsaturated hydrocarbons, followed by facile cleavage of the N-Al bond. The aluminylene formally behaves as an [Al+] cation transfer reagent in a two-step manner, and the only byproduct is a carbazolide salt that can be utilized to regenerate the aluminylene. The carbazolyl Al-heterocycles show unique luminescent properties, one of which exhibits dual emission. Our approach not only has a significant impact on the future design of single-atom addition reactions, but also paves the way for emissive materials based on Al-heterocycles

Integrated analysis reveals FLI1 regulates the tumor immune microenvironment via its cell-type-specific expression and transcriptional regulation of distinct target genes of immune cells in breast cancer

Abstract Background Immunotherapy is a practical therapeutic approach in breast cancer (BRCA), and the role of FLI1 in immune regulation has gradually been unveiled. However, the specific role of FLI1 in BRCA was conflicted; thus, additional convincing evidence is needed. Methods We explored the upstream regulation of FLI1 expression via summary data-based Mendelian randomization (SMR) analysis and ncRNA network construction centering on FLI1 using BRCA genome-wide association study (GWAS) summary data with expression quantitative trait loci (eQTLs) and DNA methylation quantitative trait loci (mQTLs) from the blood and a series of in silico analyses, respectively. We illuminated the downstream function of FLI1 in immune regulation by integrating a series of analyses of single-cell RNA sequence data (scRNA-seq). Results We verified a causal pathway from FLI1 methylation to FLI1 gene expression to BRCA onset and demonstrated that FLI1 was downregulated in BRCA. FLI1, a transcription factor, served as myeloid and T cells’ communication regulator by targeting immune-related ligands and receptor transcription in BRCA tissues. We constructed a ceRNA network centering on FLI1 that consisted of three LncRNAs (CKMT2-AS1, PSMA3-AS1, and DIO3OS) and a miRNA (hsa-miR-324-5p), and the expression of FLI1 was positively related to a series of immune-related markers, including immune cell infiltration, biomarkers of immune cells, and immune checkpoints. Conclusion Low-methylation-induced or ncRNA-mediated downregulation of FLI1 is associated with poor prognosis, and FLI1 might regulate the tumor immune microenvironment via a cell-type-specific target genes manner in BRCA

Efficient Photocatalytic Core–Shell Synthesis of Titanate Nanowire/rGO

Wide bandgap semiconductor-based photocatalysts are usually limited by their low solar energy conversion efficiency due to their limited absorption solar wavelength, their rapid surface recombination of the photogenerated electron–hole pairs, and their low charge-carrier mobility. Here, we report a novel stepwise solution synthesis for achieving a new photocatalytic core–shell consisting of a titanate nanowire/reduced graphene oxide shell (or titanate/rGO) 1D-nanocomposite. The new core–shell nanocomposite maximized the specific surface area, largely reduced the charge transfer resistance and reaction energy barrier, and significantly improved the absorption of visible light. The core–shell nanocomposites’ large on/off current ratio and rapid photo-responses boosted the photocurrent by 30.0%, the photocatalysis rate by 50.0%, and the specific surface area by 16.4% when compared with the results for the pure titanate nanowire core. Our numerical simulations support the effective charge separation on the new core–shell nanostructure, which can help further advance the novel photocatalysis

Toward the positional cloning of qBlsr5a, a QTL underlying resistance to bacterial leaf streak, using overlapping sub-CSSLs in rice.

Bacterial leaf steak (BLS) is one of the most destructive diseases in rice. Studies have shown that BLS resistance in rice is quantitatively inherited, controlled by multiple quantitative trait loci (QTLs). A QTL with relatively large effect, qBlsr5a, was previously mapped in a region of ∼ 380 kb on chromosome 5. To fine map qBlsr5a further, a set of overlapping sub-chromosome segment substitution lines (sub-CSSLs) were developed from a large secondary F2 population (containing more than 7000 plants), in which only the chromosomal region harboring qBlsr5a was segregated. By genotyping the sub-CSSLs with molecular markers covering the target region and phenotyping the sub-CSSLs with artificial inoculation, qBlsr5a was delimited to a 30.0-kb interval, in which only three genes were predicted. qRT-PCR analysis indicated that the three putative genes did not show significant response to the infection of BLS pathogen in both resistant and susceptible parental lines. However, two nucleotide substitutions were found in the coding sequence of gene LOC_Os05g01710, which encodes the gamma chain of transcription initiation factor IIA (TFIIAγ). The nucleotide substitutions resulted in a change of the 39th amino acid from valine (in the susceptible parent) to glutamic acid (in the resistant parent). Interestingly, the resistant parent allele of LOC_Os05g01710 is identical to xa5, a major gene resistant to bacterial leaf blight (another bacterial disease of rice). These results suggest that LOC_Os05g01710 is very possibly the candidate gene of qBlsr5a

Off-Hour Admission Is Associated with Poor Outcome in Patients with Intracerebral Hemorrhage

The mortality of stroke increases on weekends and during off-hour periods. We investigated the effect of off-hour admission on the outcomes of intracerebral hemorrhage (ICH) patients. We retrospectively analyzed a prospective cohort of ICH patients, admitted between January 2017 and December 2019 at the First Affiliated Hospital of Chongqing Medical University. Acute ICH within 72 h after onset with a baseline computed tomography and 3-month follow-up were included in our study. Multivariable logistic regression analysis was performed for calculating the odds ratios (OR) and 95% confidence interval (CI) for the outcome measurements. Of the 656 participants, 318 (48.5%) were admitted during on-hours, whereas 338 (51.5%) were admitted during off-hours. Patients with a poor outcome had a larger median baseline hematoma volume, of 27 mL (interquartile range 11.1–53.2 mL), and a lower median time from onset to imaging, of 2.8 h (interquartile range 1.4–9.6 h). Off-hour admission was significantly associated with a poor functional outcome at 3 months, after adjusting for cofounders (adjusted OR 2.17, 95% CI 1.35–3.47; p = 0.001). We found that patients admitted during off-hours had a higher risk of poor functional outcomes at 3 months than those admitted during working hours