Evaluation of a 12-hole clock model for improving bronchoscopic skills in simulated normal and difficult airways among anesthesia residents: A randomized controlled study.

BACKGROUND: Simulation-based training is used to improve fiberoptic bronchoscopic skills for novices. We developed a nonanatomical task trainer (named 12-hole clock model) that focused on training manipulation of bronchoscopes. The aim of this study was to evaluate the training effect of this model on bronchoscopic skills and learning interests in simulated normal and difficult airways among anesthesia residents. METHODS: Forty-three anesthesia residents without experience in bronchoscopic intubation were randomly divided into control (n = 22) and intervention groups (n = 21). All participants received standard multimedia learning and a baseline test using a normal airway manikin. Then, the control and intervention groups engaged in 60 minutes of training via a traditional airway manikin or the clock model, respectively. After training, the participants completed bronchoscopic performance assessments in simulated normal and difficult airways, as well as an electronic questionnaire related to the course. RESULTS: During training, the total hands-on time of bronchoscopic practice recorded by trainees' themselves was longer in the intervention group than in the control group (1568 ±â€…478 seconds vs 497 ±â€…172 s, P < .0001). Posttraining, the time required to visualize the carina in simulated normal airways was longer in the intervention group than in the control group (22.0 [18.0, 29.0] vs 14.0 [10.8, 18.3], P < .0001), while it was shorter for simulated difficult airways (24.0 [16.0, 32.0] s vs 27.0 [21.0, 35.5] s, P = .0425). The survey results indicated that confidence in bronchoscopic intubation increased in both groups, without significant differences in satisfaction, acceptance, or perceived difficulty between the groups. However, the interest ratings were higher in the intervention group than in the control group. CONCLUSIONS: The 12-hole clock model is a simple and feasible method for improving bronchoscopic skills and promoting interest among trainees. TRIAL REGISTRATION: NCT05327842 at Clinicaltrials.gov.

Antibiotics alter the metabolic profile of metolachlor in soil-plant system by disturbing the detoxifying process and oxidative stress.

Antibiotics are widely detected in farmland, which may influence the environmental behavior and risks of the coexisting pesticide. In this work, the effects of antibiotics on metolachlor transformation in soil-pea and the risk of metolachlor to earthworm were assessed, and the mechanism was explored in view of detoxifying process and oxidative stress. Antibiotics affected not the degradation rate but the metabolic profile of metolachlor. In soil, the content of metabolites oxaloacetic acid (OA) and ethane sulfonic acid (ESA) was decreased and dechlorometolachlor (DCL) was increased by antibiotics. In pea, the accumulation of metolachlor, DCL and ESA was decreased, while OA was increased by antibiotics. The changed transformation of metolachlor affected the risk to earthworm according to risk quote assessment. In further research, it was found that cytochrome P450 (CYP450) enzyme was reduced by 12.3% - 30.4% in soil and 12.4% - 23.6% in pea, which might due to excessive ROS accumulation induced by antibiotics, thus affecting the transformation and metabolite profile of metolachlor in soil-plant system.

Benzorhodol derived far-red/near-infrared fluorescent probes for selective and sensitive detection of butyrylcholinesterase activity in living cells and the non-alcoholic fatty liver of zebrafish.

Liver diseases are a growing public health concern and the development of non-alcoholic fatty liver disease (NAFLD) has a significant impact on human metabolism. Butyrylcholinesterase (BChE) is a vital biomarker for NAFLD, making it crucial to monitor BChE activity with high sensitivity and selectivity. In this study, we designed and synthesized a range of benzorhodol-derived far-red/near-infrared fluorescent probes, FRBN-B, NF-SB, and NF-B, for the quantitative detection and imaging of BChE. These probes differed in the size of their conjugated systems and in the number of incorporated cyclopropanecarboxylates, acting as the recognition site for BChE. Comprehensive characterization showed that FRBN-B and NF-SB fluorescence was triggered by BChE-mediated hydrolysis, while an additional cyclopropanecarboxylate in NF-B impeded the fluorescence release. High selectivity towards BChE was observed for FRBN-B and NF-SB, with a detection limit of 7.2 × 10-3 U mL-1 for FRBN-B and 1.9 × 10-3 U mL-1 for NF-SB. The probes were further employed in the evaluation of BChE inhibitor efficacy and imaging of intracellular BChE activity. Additionally, FRBN-B was utilized for imaging the BChE activity level in liver tissues in zebrafish, demonstrating its potential as a diagnostic tool for NAFLD.

Oxytocin ameliorates cognitive impairments by attenuating excitation/inhibition imbalance of neurotransmitters acting on parvalbumin interneurons in a mouse model of sepsis-associated encephalopathy.

Inflammation plays a crucial role in the initiation and progression of sepsis, and it also induces alterations in brain neurotransmission, thereby contributing to the development of sepsis-associated encephalopathy (SAE). Parvalbumin (PV) interneurons are pivotal contributors to cognitive processes in various central dysfunctions including SAE. Oxytocin, known for its ability to augment the firing rate of gamma-aminobutyric acid (GABA)ergic interneurons and directly stimulate inhibitory interneurons to enhance the tonic inhibition of pyramidal neurons, has prompted an investigation into its potential effects on cognitive dysfunction in SAE. In the current study, we administered intranasal oxytocin to the SAE mice induced by lipopolysaccharide (LPS). Behavioral assessments, including open field, Y-maze, and fear conditioning, were used to evaluate cognitive performance. Golgi staining revealed hippocampal synaptic deterioration, local field potential recordings showed weakened gamma oscillations, and immunofluorescence analysis demonstrated decreased PV expression in the cornu ammonis 1 (CA1) region of the hippocampus following LPS treatment, which was alleviated by oxytocin. Furthermore, immunofluorescence staining of PV co-localization with vesicular glutamate transporter 1 or vesicular GABA transporter indicated a balanced excitation/inhibition effect of neurotransmitters on PV interneurons after oxytocin administration in the SAE mice, leading to improved cognitive function. In conclusion, cognitive function improved after oxytocin treatment. The number of PV neurons in the hippocampal CA1 region and the balance of excitatory/inhibitory synaptic transmission on PV interneurons, as well as changes in local field potential gamma oscillations in the hippocampal CA1 region, may represent its specific mechanisms.

Identification of the coexisting virus-derived siRNA in maize and rice infected by rice black-streaked dwarf virus.

Rice black-streaked dwarf virus is transmitted by small brown planthoppers, which causes maize rough dwarf disease and rice black-streaked dwarf disease. This virus leads to slow growth or death of the host plants. During the co-evolutionary arms race between viruses and plants, virus-derived small interfering RNAs challenge the plant's defense response and inhibit host immunity through the RNA silencing system. However, it is currently unknown if rice black-streaked dwarf virus can produce the same small interfering RNAs to mediate the RNA silencing in different infected species. In this study, four small RNA libraries and four degradome libraries were constructed by extracting total RNAs from the leaves of the maize (Zea mays) inbred line B73 and japonica rice (Oryza sativa) variety Nipponbare exposed to feeding by viruliferous and non-viruliferous small brown planthoppers. We analyzed the characteristics of small RNAs and explored virus-derived small interfering RNAs in small RNA libraries through high-throughput sequencing. On analyzing the characteristics of small RNA, we noted that the size distributions of small RNAs were mainly 24-nt (19.74%-62.00%), whereas those of virus-derived small interfering RNAs were mostly 21-nt (41.06%-41.87%) and 22-nt (39.72%-42.26%). The 5'-terminal nucleotides of virus-derived small interfering RNAs tended to be adenine or uracil. Exploring the distribution of virus-derived small interfering RNAs hot spots on the viral genome segments revealed that the frequency of hot spots in B73 was higher than those in Nipponbare. Meanwhile, hotspots in the S9 and S10 virus genome segments were distributed similarly in both hosts. In addition, the target genes of small RNA were explored by degradome sequencing. Analyses of the regulatory pathway of these target genes unveiled that viral infection affected the ribosome-related target genes in maize and target genes in metabolism and biosynthesis pathways in rice. Here, 562 and 703 virus-derived small interfering RNAs were separately obtained in maize and rice, and 73 virus-derived small interfering RNAs named as co-vsiRNAs were detected in both hosts. Stem-loop PCR and RT-qPCR confirmed that co-vsiRNA 3.1 and co-vsiRNA 3.5 derived from genome segment S3 simultaneously play a role in maize and rice and inhibited host gene expression. The study revealed that rice black-streaked dwarf virus can produce the same small interfering RNAs in different species and provides a new direction for developing the new antiviral strategies.

Trichome-Like Biomimetic Air Filters via Templated Silicone Nanofilaments.

Air pollution threats to human health have increased awareness of the role of filter units in air cleaning applications. As an ideal energy-saving strategy for air filters, the slip effect on nanofiber surfaces can potentially overcome the trade-off between filtration efficiency and pressure drop. However, the potential of the slip effect in nanofibrous structures is significantly limited by the tight nanofiber stacks. In this study, trichome-like biomimetic (TLB) air filters with 3D-templated silicone nanofilaments (average diameter: ≈74 nm) are prepared based on an in situ chemical vapor deposition (CVD) method inspired by plant purification. Theoretical modeling and experimental results indicate that TLB air filters make significant use of the slip effect to overcome the efficiency-resistance tradeoff. The selectable filter class (up to U15, ≈99.9995%) allows TLB air filters to meet various requirements, and their integral filtration performance surpasses that of most commodity air filters, including melt-blown cloth, ePTFE membranes, electrospun mats, and glass fiber paper. The proposed strategy directly transforms commercial filter media and filters into TLB air filters using a bottom-up, one-step approach. As a proof-of-concept, reusable N95 respirators and air purifiers equipped with TLB air filters are fabricated, overcoming the limitations of existing filter designs and fabrication methods.

Association between coronary artery disease and clinical outcome in cancer patients: A propensity score matching analysis.

Objective: The aim of this study was to evaluate the prognostic value of coronary artery disease (CAD) detected by coronary computed tomography angiography (CTA) to predict the risk of all-cause mortality in cancer patients in a propensity score matching (PSM) analysis. Methods: A total of 331 patients who previously had cancer and underwent coronary CTA from January 2015 to December 2019 were included. Multivariate Cox proportional hazards regression analysis and propensity-score matching analysis were performed. The primary endpoint was all-cause of mortality. Results: In total, 125 with CAD and 206 with no CAD during a median follow-up of 3.3 years were included in this study. After PSM, age (HR, 1.040; 95%CI, 1.001-1.081; p = 0.014) and CAD (HR, 2.164; 95%CI, 1.057-4.430; p = 0.035) remained significant factors for all-cause mortality. Conclusion: CAD evaluated by coronary CTA was found to be at higher risk for all-cause mortality in cancer patients. Due to the retrospective design and lack of information on some medical history and treatments, especially immune checkpoint inhibitors, a large-scale prospective study is needed to further determine the prognostic value of coronary CTA in cancer patients.

Bioinspired Structures Made of Silicone Nanofilaments for Upcycling Waste Masks to Reusable N95 Respirators.

The increasing demand for personal protective equipment such as single-use masks has led to large amounts of nondegradable plastic waste, aggravating economic and environmental burdens. This study reports a simple and scalable approach for upcycling waste masks via a chemical vapor deposition technique, realizing a trichome-like biomimetic (TLB) N95 respirator with superhydrophobicity (water contact angle ≥150°), N95-level protection, and reusability. The TLB N95 respirator comprising templated silicone nanofilaments with an average diameter of ∼150 nm offers N95-level protection and breathability comparable to those of commercial N95 respirators. The TLB N95 respirator can still maintain its N95-level protection against particulate matter and viruses after 10 disinfection treatment cycles (i.e., ultraviolet irradiation, microwave irradiation, dry heating, and autoclaving), demonstrating durable reusability. The proposed strategy provides new insight into upcycle waste masks, breaking the existing design and preparation concept of reusable masks.

Enantioselective bioaccumulation and toxicological effects of chiral neonicotinoid sulfoxaflor in rats.

Sulfoxaflor is a widely used fourth-generation neonicotinoid pesticide, which has been detected in biological and environmental samples. Sulfoxaflor can potentially be exposed to humans via the food chain, thus understanding its toxic effects and enantioselective bioaccumulation is crucial. In this study, toxicokinetics, bioaccumulation, tissue distribution and enantiomeric profiles of sulfoxaflor in rats were investigated through single oral exposure and 28-days continuous exposure experiment. Sulfoxaflor mainly accumulated in liver and kidney, and the (-)-2R,3R-sulfoxaflor and (-)-2S,3R-sulfoxaflor had higher enrichment than their enantiomers in rats. The toxicological effects were evaluated after 28-days exposure. Slight inflammation in liver and kidney were observed by histopathology. Sphingolipid, amino acid, and vitamin B6 metabolism pathways were significantly disturbed in metabonomics analysis. These toxicities were in compliance with dose-dependent effects. These results improve understanding of enantioselective bioaccumulation and the potential health risk of sulfoxaflor.

Multi-omics and gut microbiome: Unveiling the pathogenic mechanisms of early-life pesticide exposure.

The extensive application of pesticides in agricultural production has raised significant concerns about its impact on human health. Different pesticides, including fungicides, insecticides, and herbicides, cause environmental pollution and health problems for non-target organisms. Infants and young children are so vulnerable to the harmful effects of pesticide exposure that early-life exposure to pesticides deserves focused attention. Recent research lays emphasis on understanding the mechanism between negative health impacts and early-life exposure to various pesticides. Studies have explored the impacts of exposure to these pesticides on model organisms (zebrafish, rats, and mice), as well as the mechanism of negative health effects, based on advanced methodologies like gut microbiota and multi-omics. These methodologies help comprehend the pathogenic mechanisms associated with early-life pesticide exposure. In addition to presenting health problems stemming from early-life exposure to pesticides and their pathogenic mechanisms, this review proposes expectations for future research. These proposals include focusing on identifying biomarkers that indicate early-life pesticide exposure, investigating transgenerational effects, and seeking effective treatments for diseases arising from such exposure. This review emphasizes how to understand the pathogenic mechanisms of early-life pesticide exposure through gut microbiota and multi-omics, as well as the adverse health effects of such exposure.

The combination of chemical fertilizer affected the control efficacy against root-knot nematode and environmental behavior of abamectin in soil.

Chemical fertilizer and pesticide are necessary in agriculture, which have been frequently used, sometimes even at the same time or in combination. To understand the interactions of them could be of significance for better use of these agrochemicals. In this study, the influence of chemical fertilizers (urea, potassium sulfate, ammonium sulfate and superphosphate) on the control efficacy and environmental behavior of abamectin was investigated, which could be applied in soil for controlling nematodes. In laboratory assays, ammonium sulfate at 1 and 2 g/L decreased the LC50 values of abamectin to Meloidogyne incognita from 0.17 mg/L to 0.081 and 0.043 mg/L, indicating it could increase the contact toxicity. In greenhouse trial, ammonium sulfate at 1000 mg/kg increased the control efficacy of abamectin by 1.37 times. Meanwhile, the combination of abamectin with ammonium sulfate could also promote the tomato seedling growth as well as the defense-related enzyme activity under M. incognita stress. The persistence and mobility of abamectin in soil were significantly elevated by ammonium sulfate, which could prolong and promote the control efficacy against nematodes. These results could provide reference for reasonable use of abamectin and fertilizers so as to increase the control efficacy and minimize the environmental risks.

CircAKT3 alleviates postoperative cognitive dysfunction by stabilizing the feedback cycle of miR-106a-5p/HDAC4/MEF2C axis in hippocampi of aged mice.

Circular RNAs (circRNAs) have garnered significant attention in the field of neurodegenerative diseases including Alzheimer's diseases due to their covalently closed loop structure. However, the involvement of circRNAs in postoperative cognitive dysfunction (POCD) is still largely unexplored. To identify the genes differentially expressed between non-POCD (NPOCD) and POCD mice, we conducted the whole transcriptome sequencing initially in this study. According to the expression profiles, we observed that circAKT3 was associated with hippocampal neuronal apoptosis in POCD mice. Moreover, we found that circAKT3 overexpression reduced apoptosis of hippocampal neurons and alleviated POCD. Subsequently, through bioinformatics analysis, our data showed that circAKT3 overexpression in vitro and in vivo elevated the abundance of miR-106a-5p significantly, resulting in a decrease of HDAC4 protein and an increase of MEF2C protein. Additionally, this effect of circAKT3 was blocked by miR-106a-5p inhibitor. Interestingly, MEF2C could activate the transcription of miR-106a-5p promoter and form a positive feedback loop. Therefore, our findings revealed more potential modulation ways between circRNA-miRNA and miRNA-mRNA, providing different directions and targets for preclinical studies of POCD.

ZmADF5, a Maize Actin-Depolymerizing Factor Conferring Enhanced Drought Tolerance in Maize.

Drought stress is seriously affecting the growth and production of crops, especially when agricultural irrigation still remains quantitatively restricted in some arid and semi-arid areas. The identification of drought-tolerant genes is important for improving the adaptability of maize under stress. Here, we found that a new member of the actin-depolymerizing factor (ADF) family; the ZmADF5 gene was tightly linked with a consensus drought-tolerant quantitative trait locus, and the significantly associated signals were detected through genome wide association analysis. ZmADF5 expression could be induced by osmotic stress and the application of exogenous abscisic acid. Its overexpression in Arabidopsis and maize helped plants to keep a higher survival rate after water-deficit stress, which reduced the stomatal aperture and the water-loss rate, as well as improved clearance of reactive oxygen species. Moreover, seventeen differentially expressed genes were identified as regulated by both drought stress and ZmADF5, four of which were involved in the ABA-dependent drought stress response. ZmADF5-overexpressing plants were also identified as sensitive to ABA during the seed germination and seedling stages. These results suggested that ZmADF5 played an important role in the response to drought stress.

Nitrogen fertiliser-domesticated microbes change the persistence and metabolic profile of atrazine in soil.

Pesticides and fertilisers are frequently used and may co-exist on farmlands. The overfertilisation of soil may have a profound influence on pesticide residues, but the mechanism remains unclear. The effects of chemical fertilisers on the environmental behaviour of atrazine and their underlying mechanisms were investigated. The present outcomes indicated that the degradation of atrazine was inhibited and the half-life was prolonged 6.0 and 7.6 times by urea and compound fertilisers (NPK) at 1.0 mg/g (nitrogen content), respectively. This result, which was confirmed in both sterilised and transfected soils, was attributed to the inhibitory effect of nitrogen fertilisers on soil microorganisms. The abundance of soil bacteria was inhibited by nitrogen fertilisers, and five families of potential atrazine degraders (Micrococcaceae, Rhizobiaceae, Bryobacteraceae, Chitinophagaceae, and Sphingomonadaceae) were strongly and positively (R > 0.8, sig < 0.05) related to the decreased functional genes (atzA and trzN), which inhibited hydroxylation metabolism and ultimately increased the half-life of atrazine. In addition, nitrogen fertilisers decreased the sorption and vertical migration behaviour of atrazine in sandy loam might increase the in-situ residual and ecological risk. Our findings verified the weakened atrazine degradation with nitrogen fertilisers, providing new insights into the potential risks and mechanisms of atrazine in the context of overfertilisation.

Oxytetracycline Increases the Residual Risk of Imidacloprid in Radish (Raphanus sativus) and Disturbs the Plant-Rhizosphere Microbiome Holobiont Homeostasis.

Antibiotics can be accidentally introduced into farmland by wastewater irrigation, and the environmental effects are still unclear. In this study, the effects of oxytetracycline on the residue of imidacloprid in soil and radishes were investigated. Besides, the rhizosphere microbiome and radish metabolome were analyzed. It showed that the persistence of imidacloprid in soil was unchanged, but the content of olefin-imidacloprid was increased by oxytetracycline. The residue of imidacloprid in radishes was increased by nearly 1.5 times, and the hazard index of imidacloprid was significantly raised by 1.5-4 times. Oxytetracycline remodeled the rhizosphere microbiome, including Actinobe, Elusimic, and Firmicutes, and influenced the metabolome of radishes. Especially, some amino acid metabolic pathways in radish were downregulated, which might be involved in imidacloprid degradation. It can be assumed that oxytetracycline increased the imidacloprid residue in radish through disturbing the plant-rhizosphere microbiome holobiont and, thus, increased the pesticide dietary risk.

Gene pyramiding of ZmGLK36 and ZmGDIα-hel for rough dwarf disease resistance in maize.

Maize rough dwarf disease (MRDD) caused by pathogenic viruses in the genus Fijivirus in the family Reoviridae is one of the most destructive diseases in maize. The pyramiding of effective resistance genes into maize varieties is a potential approach to reduce the damage resulting from the disease. Two major quantitative trait loci (QTLs) (qMrdd2 and qMrdd8) have been previously identified. The resistance genes ZmGLK36 and ZmGDIα-hel have also been cloned with the functional markers Indel-26 and IDP25K, respectively. In this study, ZmGLK36 and ZmGDIα-hel were introgressed to improve MRDD resistance of maize lines (Zheng58, Chang7-2, B73, Mo17, and their derived hybrids Zhengdan958 and B73 × Mo17) via marker-assisted selection (MAS). The converted lines and their derived hybrids, carrying one or two genes, were evaluated for MRDD resistance using artificial inoculation methods. The double-gene pyramiding lines and their derived hybrids exhibited increased resistance to MRDD compared to the monogenic lines and the respective hybrids. The genetic backgrounds of the converted lines were highly similar (90.85-98.58%) to the recurrent parents. In addition, agronomic trait evaluation demonstrated that pyramiding lines with one or two genes and their derived hybrids were not significantly different from the recurrent parents and their hybrids under nonpathogenic stress, including period traits (tasseling, pollen shedding, and silking), yield traits (ear length, grain weight per ear and 100-kernel weight) and quality traits (protein and starch content). There were differences in plant architecture traits between the improved lines and their hybrids. This study illustrated the successful development of gene pyramiding for improving MRDD resistance by advancing the breeding process. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01466-9.

Multifaceted Effects of Subchronic Exposure to Chlorfenapyr in Mice: Implications from Serum Metabolomics, Hepatic Oxidative Stress, and Intestinal Homeostasis.

As chlorfenapyr is a commonly used insecticide in agriculture, the health risks of subchronic exposure to chlorfenapyr remained unclear. This study aimed to extensively probe the health risks from subchronic exposure to chlorfenapyr at the NOAEL and 10-fold NOAEL dose in mice. Through pathological and biochemical examinations, the body metabolism, hepatic toxicity, and intestinal homeostasis were systematically assessed. After 12 weeks, a 10-fold NOAEL dose of chlorfenapyr resulted in weight reduction, increased daily food intake, and blood lipid abnormalities. Concurrently, this dosage induced hepatotoxicity and amplified oxidative stress in hepatocytes, a finding further supported in HepG2 cells. Moreover, chlorfenapyr resulted in intestinal inflammation, evidenced by increased inflammatory factors (IL-17a, IL-10, IL-1ß, IL-6, IL-22), disrupted immune cells (RORγt, Foxp3), and compromised intestinal barriers (ZO-1 and occludin). By contrast, the NOAEL dose presented less toxicity in most evaluations. Serum metabolomic analyses unveiled widespread disruptions in pathways related to hepatotoxicity and intestinal inflammation, including NF-κB signaling, Th cell differentiation, and bile acid metabolism. Microbiomic analysis showed an increase in Lactobacillus, a decrease in Muribaculaceae, and diminished anti-inflammatory microbes, which further propelled the inflammatory response and leaded to intestinal inflammation. These findings revealed the molecular mechanisms underlying chlorfenapyr-induced hepatotoxicity and intestinal inflammation, highlighting the significant role of the gut microbiota.

Development of interpretable machine learning models for prediction of acute kidney injury after noncardiac surgery: a retrospective cohort study.

BACKGROUND: Early identification of patients at high-risk of postoperative acute kidney injury (AKI) can facilitate the development of preventive approaches. This study aimed to develop prediction models for postoperative AKI in noncardiac surgery using machine learning algorithms. The authors also evaluated the predictive performance of models that included only preoperative variables or only important predictors. MATERIALS AND METHODS: Adult patients undergoing noncardiac surgery were retrospectively included in the study (76 457 patients in the discovery cohort and 11 910 patients in the validation cohort). AKI was determined using the KDIGO criteria. The prediction model was developed using 87 variables (56 preoperative variables and 31 intraoperative variables). A variety of machine learning algorithms were employed to develop the model, including logistic regression, random forest, extreme gradient boosting, and gradient boosting decision trees. The performance of different models was compared using the area under the receiver operating characteristic curve (AUROC). Shapley Additive Explanations (SHAP) analysis was employed for model interpretation. RESULTS: The patients in the discovery cohort had a median age of 52 years (IQR: 42-61 years), and 1179 patients (1.5%) developed AKI after surgery. The gradient boosting decision trees algorithm showed the best predictive performance using all available variables, or only preoperative variables. The AUROCs were 0.849 (95% CI: 0.835-0.863) and 0.828 (95% CI: 0.813-0.843), respectively. The SHAP analysis showed that age, surgical duration, preoperative serum creatinine, and gamma-glutamyltransferase, as well as American Society of Anesthesiologists physical status III were the most important five features. When gradually reducing the features, the AUROCs decreased from 0.852 (including the top 40 features) to 0.839 (including the top 10 features). In the validation cohort, the authors observed a similar pattern regarding the models' predictive performance. CONCLUSIONS: The machine learning models the authors developed had satisfactory predictive performance for identifying high-risk postoperative AKI patients. Furthermore, the authors found that model performance was only slightly affected when only preoperative variables or only the most important predictive features were included.

Repeated (S)-ketamine administration ameliorates the spatial working memory impairment in mice with chronic pain: role of the gut microbiota-brain axis.

Chronic pain is commonly linked with diminished working memory. This study explores the impact of the anesthetic (S)-ketamine on spatial working memory in a chronic constriction injury (CCI) mouse model, focusing on gut microbiome. We found that multiple doses of (S)-ketamine, unlike a single dose, counteracted the reduced spontaneous alteration percentage (%SA) in the Y-maze spatial working memory test, without affecting mechanical or thermal pain sensitivity. Additionally, repeated (S)-ketamine treatments improved the abnormal composition of the gut microbiome (ß-diversity), as indicated by fecal 16S rRNA analysis, and increased levels of butyrate, a key gut - brain axis mediator. Protein analysis showed that these treatments also corrected the upregulated histone deacetylase 2 (HDAC2) and downregulated brain-derived neurotrophic factor (BDNF) in the hippocampi of CCI mice. Remarkably, fecal microbiota transplantation from mice treated repeatedly with (S)-ketamine to CCI mice restored %SA and hippocampal BDNF levels in CCI mice. Butyrate supplementation alone also improved %SA, BDNF, and HDAC2 levels in CCI mice. Furthermore, the TrkB receptor antagonist ANA-12 negated the beneficial effects of repeated (S)-ketamine on spatial working memory impairment in CCI mice. These results indicate that repeated (S)-ketamine administration ameliorates spatial working memory impairment in CCI mice, mediated by a gut microbiota - brain axis, primarily through the enhancement of hippocampal BDNF - TrkB signaling by butyrate.