Perioperative neurocognitive disorders (PND) with a high incidence frequently occur in elderly surgical patients closely associated with prolonged anesthesia-induced neurotoxicity. The ...neuromorphopathological underpinnings of anesthesia-induced neurotoxicity have remained elusive.
Prolonged anesthesia with sevoflurane was used to establish the sevoflurane-induced neurotoxicity (SIN) animal model. Morris water maze, elevated plus maze, and open field test were employed to track SIN rats' cognitive behavior and anxiety-like behaviors. We investigated the neuropathological basis of SIN through techniques such as transcriptomic, electrophysiology, molecular biology, scanning electron microscope, Golgi staining, TUNEL assay, and morphological analysis. Our work further clarifies the pathological mechanism of SIN by depleting microglia, inhibiting neuroinflammation, and C1q neutralization.
This study shows that prolonged anesthesia triggers activation of the NF-κB inflammatory pathway, neuroinflammation, inhibition of neuronal excitability, cognitive dysfunction, and anxiety-like behaviors. RNA sequencing found that genes of different types of synapses were downregulated after prolonged anesthesia. Microglial migration, activation, and phagocytosis were enhanced. Microglial morphological alterations were also observed. C1qa, the initiator of the complement cascade, and C3 were increased, and C1qa tagging synapses were also elevated. Then, we found that the "Eat Me" complement pathway mediated microglial synaptic engulfment in the hippocampus after prolonged anesthesia. Afterward, synapses were remarkably lost in the hippocampus. Furthermore, dendritic spines were reduced, and their genes were also downregulated. Depleting microglia ameliorated the activation of neuroinflammation and complement and rescued synaptic loss, cognitive dysfunction, and anxiety-like behaviors. When neuroinflammatory inhibition or C1q neutralization occurred, complement was also decreased, and synaptic elimination was interrupted.
These findings illustrated that prolonged anesthesia triggered neuroinflammation and complement-mediated microglial synaptic engulfment that pathologically caused synaptic elimination in SIN. We have demonstrated the neuromorphopathological underpinnings of SIN, which have direct therapeutic relevance for PND patients.
Wood has a natural three-dimensional porous structure. As one main component of wood, lignin is rich in a variety of reducing functional groups which can in situ reduce Au (III) into Au (0). Through ...this efficient, green and convenient method, gold nanoparticles (Au NPs) were generated and anchored in Paulownia
Sieb. et Zucc.
Chip to fabricate an Au NP/Wood membrane reactor. The characterization of Au NP/Wood by SEM, XRD and XPS showed that Au NPs were uniformly dispersed in wood. The catalytic capacity of the reactor for the reduction of methylene blue (MB) and 4-nitrophenol (4-NP) were evaluated. The Au NP/Wood exhibited the substantial catalytic capacity and the reaction rate constants were 0.162 min
−1
and 0.152 min
−1
, respectively. As the filter membrane, the flowing catalytic capacity investigation revealed that the hydrogenation of MB and 4-NP was over 98% as the flux was 0.973 × 10
3
L/m
2
·h. Even after eight cycles, the catalytic capacity of the membrane slightly decreased, while the hydrogenation still remained above 90%. This green synthetic Au NP/Wood has proved to be a viable and potential material for the treatment of dyes and nitroaromatic pollutants, in addition, using wood as a feedstock provides a sustainable feature of this work.
Lignin nanoparticles (LNPs) were employed as the reducing and stabilizing agent in the preparation of silver nanoparticles (Ag NPs) from silver nitrate under solar light. The Ag NPs were ...characterized by spectrophotometry, TEM, HRTEM, element mapping, XRD and XPS. The formation of Ag NPs and the structural changes of lignin during the reaction was monitored by analysis via
31
P NMR,
1
H NMR and
13
C NMR. The Ag NPs have uniform shape and an average size of ~14 nm. They were loaded onto the surface of LNPs and entangled in lignin. The resulting Ag NP-LNP suspension displays an ultrasensitive and selective optical response to Hg (II) in giving a color change from yellow to colorless. The assay was performed by spectrophotometry at 450 nm. The analytically useful range extends from 5 nM to 100 nM of Hg (II), and the limit of detection is 1.4 nM in deionized water and 1.8 nM in spiked tap water. This is lower than the threshold level (10 nM) in drinking water specified by the US Environmental Protection Agency.
Graphical abstract
Schematic representation of the solar light induced synthesis of sliver nanoparticles (Ag NPs) by lignin nanoparticles (LNPs) and their application to colorimetric determination of Hg
2+
.
Circadian rhythm involved with physiology has been reported to affect pharmacokinetics or pharmacodynamics. We hypothesized that circadian variations in physiology disturb anesthesia and eventually ...affect recovery after anesthesia.
A retrospective cohort study initially included 107,406 patients (1 June 2016-6 June 2021). Patients were classified into morning or afternoon surgery groups. The primary outcome was daytime variation in PACU (post-anesthesia care unit) recovery time and Steward score. Inverse probability weighting (IPW) approach based on propensity score and univariable/multivariable linear regression were used to estimate this outcome.
Of 28,074 patients, 13,418 (48%) patients underwent morning surgeries, and 14,656 (52%) patients underwent afternoon surgeries. LOWESS curves and IPW illustrated daytime variation in PACU recovery time and Steward score. Before adjustment, compared to morning surgery group, afternoon surgery group had less PACU recovery time (median interquartile range, 57 46, 70 vs. 54 43, 66, p < 0.001) and a higher Steward score (5.62 5.61, 5.63 vs. 5.66 5.65, 5.67, p < 0.001). After adjustment, compared to morning surgery group, afternoon surgery group had less PACU recovery time (58 46, 70 vs. 54 43, 66, p < 0.001). In multivariable linear regression, morning surgery is statistically associated with an increased PACU recovery time (coefficient, −3.20; 95% confidence interval, −3.55 to −2.86).
Among non-cardiac surgeries, daytime variation might affect recovery after general anesthesia. These findings indicate that the timing of surgery improves recovery after general anesthesia, with afternoon surgery providing protection.
KEY MESSAGES
In this retrospective cohort study of 28,074 participants, the afternoon surgery group has a higher Steward score than the morning surgery group.
In multivariable linear regression, morning surgery is statistically associated with an increased PACU recovery time.
Among non-cardiac surgeries, daytime variation affects the recovery after general anesthesia, with afternoon surgery providing protection.
The natural wood can be used as a multifunctional material e.g. a reducing agent and a stabilizer due to the reducing functional groups and three-dimensional network structure. In this work, a wood ...catalyst decorated with silver nanoparticles (Ag NPs) was prepared and used to catalyze the hydrogenation of azo dyes. The systematic characterizations revealed that the Ag NPs were uniformly present on the wood surface. The Ag NP/wood exhibited an excellent catalytic activity for hydrogenating methyl orange (MO), congo red (CR) and erichrome black T (EBT), and their reaction rate constants were calculated as 1.533, 0.969 and 0.707 min−1, respectively. The factors affecting the hydrogenation efficiency of azo dyes were elucidated by the density functional theory (DFT). The catalyst had a good reusability, for instance the hydrogenation efficiency of MO retained as 90% in 5 min after six recycles. In addition, the mechanism of MO hydrogenated by NaBH4 catalyzed with the Ag NPs/wood was proposed.
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•Ag NP/wood was prepared using wood as a carrier in a green and simple method.•The formation of Ag-H promoted the cleavage of -NN- in azo dyes.•The factors of different hydrogenation rates of azo dyes were calculated by DFT.
Lignin, as a main factor inhibiting the enzymatic hydrolysis of lignocellulose, was investigated by comparing lignin isolated from untreated and pretreated lignocellulose to elucidate the differences ...in the enzyme adsorption ability. The nonproductive adsorption of cellulase on lignin was investigated by using a quartz crystal microbalance with dissipation. The results indicated that more cellulase adsorbed on the lignin isolated from autohydrolysis and green liquor-pretreated lignocellulose than on protolignin. Higher temperature and enzyme concentration increased the initial adsorption rate and the amount of enzyme adsorbed on lignin. A dynamic equation for enzyme adsorption on lignin was established. The adsorption of enzymes on lignin increased as the content of phenolic hydroxyl groups, and β-β and β-5 linkages in the lignin increased, attributed to enhanced hydrogen bonding and hydrophobic interaction. Consequently, inhibition of the enzymatic hydrolysis of cellulose was promoted by a higher phenolic hydroxyl group, β-β, and β-5 content. The adsorption of the enzyme components on lignin followed the order: β-glucosidase > xylanase >
endo
-glucanase > cellobiohydrolase, as revealed by polyacrylamide gel electrophoresis analysis. Electrostatic interaction increased the adsorption of β-glucosidase and xylanase on lignin, while synergistic hydrophobic interaction and hydrogen bonding increased the adsorption of
endo
-glucanase and cellobiohydrolase on lignin. The results indicate that the adsorption of enzymes on lignin is affected by the structure of lignin and the composition of the enzymes. The findings of the current study provide fundamental knowledge for improving the enzymatic conversion of lignocellulose.
Abstract Background Tracheal tube cuff pressure will increase after pneumoperitoneum when the cuff is inflated with air, high pressure can cause tracheal mucosal damage. This prospective trial aimed ...to assess if inflating with normal saline or lidocaine can prevent increase of tracheal tube cuff pressure and tracheal mucosal damage in laparoscopic surgeries with general anesthesia. Whether changes of tracheal tube cuff transverse diameter (CD) can predict changes of tracheal tube cuff pressure. Methods Ninety patients scheduled for laparoscopic resection of colorectal neoplasms under general anesthesia were randomly assigned to groups air (A), saline (S) or lidocaine (L). Endotracheal tube cuff was inflated with room-temperature air in group A ( n = 30), normal saline in group S ( n = 30), 2% lidocaine hydrochloride injection in group L ( n = 30). After intubation, tracheal tube cuff pressure was monitored by a calibrated pressure transducers, cuff pressure was adjusted to 25 cmH 2 O (T 0.5 ). Tracheal tube cuff pressure at 15 min after pneumoperitoneum (T 1 ) and 15 min after exsufflation (T 2 ) were accessed. CD were measured by ultrasound at T 0.5 and T 1 , the ability of ΔCD (T 1-0.5 ) to predict cuff pressure was accessed. Tracheal mucous injury at the end of surgery were also recorded. Results Tracheal tube cuff pressure had no significant difference among the three groups at T 1 and T 2 . ΔCD had prediction value (AUC: 0.92 95% CI: 0.81–1.02; sensitivity: 0.99; specificity: 0.82) for cuff pressure. Tracheal mucous injury at the end of surgery were 0 (0, 1.0) in group A, 0 (0, 1.0) in group S, 0 (0, 0) in group L ( p = 0.02, group L was lower than group A and S, p = 0.03 and p = 0.04). Conclusions Compared to inflation with air, normal saline and 2% lidocaine cannot ameliorate the increase of tracheal tube cuff pressure during the pneumoperitoneum period under general anesthesia, but lidocaine can decrease postoperative tracheal mucosa injury. ΔCD measured by ultrasound is a predictor for changes of tracheal tube cuff pressure. Trial registration Chinese Clinical Trial Registry, identifier: ChiCTR2100054089, Date: 08/12/2021.
DNA is subject to a range of endogenous and exogenous insults that can impair DNA replication and lead to DNA double-strand breaks (DSBs). The repair capacity of cancer cells mediates their ...radiosensitivity, but the roles of miR-1587 during radiation resistance are poorly characterized. In this study, we explored whether miR-1587 regulates the growth and radiosensitivity of colorectal cancer (CRC) cells through its ability to regulate DNA Ligase4 (LIG4). We found that CRC cells in which miR-1587 was overexpressed inhibited cell growth and promoted apoptosis through increasing DSBs and promoting cell cycle arrest. We found that overexpression of miR-1587 significantly inhibited LIG4 messenger RNA and protein expression and further revealed the ability of miR-1587 to directly bind to the LIG4-3′-untranslated region through dual-luciferase reporter assays. More notably, miR-1587 mimics increased the radiosensitivity of CRC cells. Taken together, we show that miR-1587 overexpression enhances the formation of DSBs, arrests CRC cell growth, and enhances the radiosensivity of CRC cells through the direct repression of LIG4 expression. These results reveal novel roles for miR-1587 during DNA damage repair and the radiosensivity of CRC cells. This highlights miR-1587 as a novel therapeutic target for CRC.
Lignin is the second largest naturally renewable resource and is primarily a by-product of the pulp and paper industry; however, its inefficient use presents a challenge. In this work, Fe
3
O
4
...nanoparticles loaded on lignin nanoparticles (Fe
3
O
4
@LNPs) were prepared by the self-assembly method and it possessed an enhanced peroxidase-like activity. Fe
3
O
4
@LNPs catalyzed the oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB) in the presence of H
2
O
2
to generate a blue color, was observable by the naked eye. Under the optimal conditions, Fe
3
O
4
@LNPs showed the ability of sensitive colorimetric detection of H
2
O
2
within a range of 5–100 μM and the limit of detection was 2 μM. The high catalytic activity of Fe
3
O
4
@LNPs allows its prospective use in a wide variety of applications, including clinical diagnosis, food safety, and environmental monitoring.
Clinical and animal studies demonstrated that neuroinflammation from anesthesia (sevoflurane) is the main contributor to cause perioperative neurocognitive disorders (PND). Recently, it was reported ...that microglia respond to hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, which was the target of sevoflurane. Whether HCN channels are involved in the induction of neuroinflammation after sevoflurane exposure is still unclear. Sevoflurane exposure had increased cognitive dysfunction and anxiety-like behaviors in rats. Rats inhaled with sevoflurane had activated microglia and increased neuroinflammation (IL-1beta, IL-6, and TNF-alpha) in the hippocampus. RNA sequencing identified 132 DEGs (86 up-regulated and 46 down-regulated DEGs differentially expressed genes) in the hippocampus of PND rats. RNA-sequencing also uncovered that sevoflurane exposure down-regulates HCN2 expression. Pathway and process enrichment analysis suggests DEGs are mainly enriched in regulation of system process, positive regulation of glutamate secretion, secretion, regulation of synaptic transmission, regulation of nervous system process, behavior, negative regulation of sodium ion transport, and learning or memory. We validated that sevoflurane exposure can down-regulate the levels of PEX5R/Trip8b (an interaction partner and auxiliary subunit of HCN channels) and HCN1-4 channels in the hippocampus of PND rats. We used immunofluorescence staining to identify that HCN2 co-labels with neurons (Neun), astrocytes (GFAP), and microglia (iba1). We observed that the co-labeling of HCN2 with neurons or microglia decreased in the hippocampus and cortex after sevoflurane exposure. Blocking HCN2 by ZD7288 treatment further activated microglia and aggravated sevoflurane exposure-induced anxiety-like behavior, cognitive impairment, and neuroinflammation. We concluded that sevoflurane exposure can induce an increased level of neuroinflammation, microglial activation, cognitive dysfunction, and anxiety-like behaviors in rats. HCN2 channel, as the target of sevoflurane action, mediates this process. HCN2 might be a target for the treatment and prevention of sevoflurane-induced PND.
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