Mapping the heterogeneous removal landscape of wastewater virome in effluents of different advanced wastewater treatment systems of swine farm.

In advanced wastewater treatment plants on pig farms, meticulous design aims to eliminate intrinsic pollutants such as organic matter, heavy metals, and biological contaminants. In our field survey across Southern China, a notable disparity in wastewater treatment procedures among various farming facilities lies in the utilization of terminal chemical oxidation post-sedimentation tank. However, recent focus in wastewater surveillance has predominantly centered on antibiotic resistance genes, leaving the efficacy of virus removal in different effluent systems largely unexplored. To profile virus composition at the effluent, assess the virus elimination efficiency of chemical oxidation at the effluent end, and the potential environmental driver of virus abundance, we deployed a meta-transcriptomics approach to first determine the total virome in effluent specimens of terminal clean water tank system (CWT) and terminal chemical oxidation system (TCO) in Southern China pig farms, respectively. From these data, 172 viruses were identified, with a median reads per million (RPM) of 27,789 in CWT and 19,982 in TCO. Through the integration of analyses encompassing the co-occurrence patterns within viral communities, the ecology of viral diversity, and a comparative assessment of average variation degrees, we have empirically demonstrated that the procedure of TCO may perturb viral communities and diminish their abundance, particularly impacting RNA viral communities. However, despite the diminished abundance, pathogenic viruses such as PEDV and PRRSV persisted in the effluent following chemical deoxidation at a moderate RPM value, indicating a substantial in situ presence at effluent. Our environmental driver modeling, employing GLM and mantel tests, substantiated the intricate nature of virus community variation within the effluent, influenced heterogeneously by diverse factors. Notably, pond temperature emerged as the foremost determinant, while fishing farming exhibited a positive correlation with virus diversity (p < 0.05). This revelation of the cryptic persistence of virus communities in wastewater effluent expands our understanding of the varied responses of different virus categories to oxidation. Such insights transcend mere virus characterization, offering valuable implications for enhancing biosafety measures in farming practices and informing wastewater-based epidemiological surveillance.

Spontaneous and chaperone-assisted metal loading in the active site of protein phosphatase-1.

Protein phosphatase PP1 has two active-site metals (Zn2+/Fe2+) that are essential for catalysis. However, when expressed in bacteria, PP1 has two Mn2+-ions in its active site, indicating that the incorporation of Zn2+/Fe2+ depends on additional eukaryotic component(s). Here, we used purified, metal-deficient PP1 to study metal incorporation. Fe2+ was incorporated spontaneously, but Zn2+ was not. Mn2+-incorporation at physiological pH depended on the co-expression of PP1 with PPP1R2 (Inhibitor-2) or PPP1R11 (Inhibitor-3), or a pre-incubation of PP1 at pH 4. We also demonstrate that PPP1R2 and PPP1R11 are Zn2+-binding proteins but are, by themselves, not able to load PP1 with Zn2+. Our data suggest that PPP1R2 and PPP1R11 function as metal chaperones for PP1 but depend on co-chaperone(s) and/or specific modification(s) for the transfer of associated Zn2+ to PP1.

Generation of advanced glycation end products from glycated protein or fructose/glyoxal-protein adducts under in vitro simulated gastrointestinal digestion.

Advanced glycation end products (AGEs) are a heterogeneous group of compounds formed both endogenously and exogenously through reactions between reducing sugars and amino acids within the proteins. The digestive tract may also serve as a site for endogenous AGEs generation. This study examined whether additional AGEs are formed during the digestion of glycated protein diets and meal-resembling systems (dietary proteins with fructose or glyoxal). The digestion of glycated protein showed that free AGEs were gradually released, but no additional AGEs were generated. In contrast, co-digestion of dietary proteins with fructose or glyoxal resulted in the formation of additional AGEs, and the reaction substrates (fructose or glyoxal) were depleted during digestion. Additionally, the lysine released from proteins decreased, leading to a loss of nutritional value of the food during co-digestion. The formation of AGEs and the depletion of essential amino acids in the gut may have significant implications for human health.

Reliability and validity of the Chinese version of the Benefit Finding Questionnaire for people with mental disorders.

BACKGROUND: Benefit finding (BF) is correlated with mental health and recovery, and its presence will contribute to the recovery of patients with mental disorders. Most of the current tools for assessing BF in patients with somatic disorders are not adequate for patients with mental disorders. The present study proposes to introduce the Benefit Finding Questionnaire for People with Mental Disorders and to validate its psychometric properties. METHODS: The Beaton translation model was used to translate and cross-culturally adjust the Japanese version of the Benefit Finding Questionnaire for People with Mental Disorders. A survey of 514 people with mental disorders was conducted from January 2022 to October 2022 using a general information questionnaire and a translated Chinese version of the Benefit Finding Questionnaire for People with Mental Disorders (BFQ-C) using a convenience sampling method. The quality of the questionnaire was examined in terms of item analysis, reliability, and validity. RESULTS: The results of the item analysis showed that all items met the requirements. The interrater agreement of the BFQ-C was good, with an interrater agreement = 0.714; the values of the item-level content validity index ranged from 0.75 to 1.00; and the average of all item-level content validity index on the scale = 0.958. Exploratory factor analysis extracted three main factors "change in relationship with others," "change in spirituality," and "change in values and thinking styles"-and the cumulative variance contribution rate was 57.70%. The results of the confirmatory factor analysis were χ2/df of 2.194, Root Mean Square Error of Approximation of 0.075, and comparative fit index of 0.919, indicating that the model fitted well. The questionnaire had a Cronbach' alpha of 0.936, a split reliability of 0.956, and a retest reliability of 0.939. CONCLUSION: The BFQ-C demonstrated good reliability and validity, and can be used to assess the BF level of people with mental disorders (e.g., anxiety disorders, depressive disorders, schizophrenia, and bipolar disorders) in China.

Predicting clinically significant prostate cancer in elderly patients: A nomogram approach with shear wave elastography.

PURPOSE: This study was to construct a nomogram utilizing shear wave elastography and assess its efficacy in detecting clinically significant prostate cancer (csPCa). METHODS: 290 elderly people with suspected PCa who received prostate biopsy and shear wave elastography (SWE) imaging were respectively registered from April 2022 to December 2023. The elderly participants were stratified into two groups: those with csPCa and those without csPCa, which encompassed cases of clinically insignificant prostate cancer (cisPCa) and non-prostate cancer tissue, as determined by pathology findings. The LASSO algorithm, known as the least absolute shrinkage and selection operator, was utilized to identify features. Logistic regression analysis was utilized to establish models. Receiver operating characteristic (ROC) and calibration curves were utilized to evaluate the discriminatory ability of the nomogram. Bootstrap (1000 bootstrap iterations) was employed for internal validation and comparison with two models. A decision curve and a clinical impact curve were employed to assess the clinical usefulness. RESULTS: Our nomogram, which contained Emean, ΔEmean, prostate volume, prostate-specific antigen density (PSAD), and transrectal ultrasound (TRUS), showed better discrimination (AUC = 0.89; 95% CI: 0.83-0.94), compared to the clinical model without SWE parameters (p = 0.0007). Its accuracy, sensitivity and specificity were 0.83, 0.89 and 0.78, respectively. Based on the analysis of decision curve, the thresholds ranged from 5% to 90%. According to our nomogram, biopsying patients at a 20% probability threshold resulted in a 25% reduction in biopsies without missing any csPCa. The clinical impact curve demonstrated that the nomogram's predicted outcome is closer to the observed outcome when the probability threshold reaches 20% or greater. CONCLUSION: Our nomogram demonstrates efficacy in identifying elderly individuals with clinically significant prostate cancer, thereby facilitating informed clinical decision-making based on diagnostic outcomes and potential clinical benefits.

Sequential system based on ferritin delivery system and cell therapy for modulating the pathological microenvironment and promoting recovery.

The vicious crosstalk among capillarization of hepatic sinusoidal endothelial cells (LSECs), activation of hepatic stellate cells (aHSCs), and hepatocyte damage poses a significant impediment to the successful treatment of liver fibrosis. In this study, we propose a sequential combination therapy aimed at disrupting the malignant crosstalk and reshaping the benign microenvironment while repairing damaged hepatocytes to achieve effective treatment of liver fibrosis. Firstly, H-subunit apoferrin (Ferritin) was adopted to load platycodonin D (PLD) and MnO2, forming ferritin@MnO2/PLD (FMP) nanoparticles, which exploited the high affinity of ferritin for the highly expressed transferrin receptor 1 (TfR1) to achieve the precise targeted delivery of FMP in the liver. Upon PLD intervention, restoration of the fenestration pores in capillarized LSECs was facilitated by modulating the phosphatidyl inositol 3-kinase/protein kinase B (PI3K/AKT) and Kruppel Like Factor 2 (KLF2) signaling pathways both in vitro and in vivo, enabling efficient entry of FMP into the Disse space. Subsequently, FMP NPs effectively inhibited HSC activation by modulating the TLR2/TLR4/NF-κB-p65 signaling pathway. Moreover, FMP NPs efficiently scavenged reactive oxygen species (ROS) and mitigated the expression of inflammatory mediators, thereby reshaping the microenvironment to support hepatocyte repair. Finally, administration of bone marrow mesenchymal stem cells (BMMSCs) was employed to promote the regeneration and functional recovery of damaged hepatocytes. In conclusion, the combined sequential therapy involving FMP and BMMSCs effectively attenuated liver fibrosis induced by CCl4 administration, resulting in significant amelioration of the fibrotic condition. The therapeutic strategy outlined in this study underscores the significance of disrupting the deleterious cellular interactions and remodeling the microenvironment, thereby presenting a promising avenue for clinical intervention in liver fibrosis.

Calmodulin Triggers Activity-Dependent rRNA Biogenesis via Interaction with DDX21.

Protein synthesis in response to neuronal activity, known as activity-dependent translation, is critical for synaptic plasticity and memory formation. However, the signaling cascades that couple neuronal activity to the translational events remain elusive. In this study, we identified the role of calmodulin (CaM), a conserved Ca2+-binding protein, in ribosomal RNA (rRNA) biogenesis in neurons. We found the CaM-regulated rRNA synthesis is Ca2+-dependent and necessary for nascent protein synthesis and axon growth in hippocampal neurons. Mechanistically, CaM interacts with nucleolar DEAD (Asp-Glu-Ala-Asp) box RNA helicase (DDX21) in a Ca2+-dependent manner to regulate nascent rRNA transcription within nucleoli. We further found CaM alters the conformation of DDX21 to liberate the DDX21-sequestered RPA194, the catalytic subunit of RNA polymerase I, to facilitate transcription of ribosomal DNA. Using high-throughput screening, we identified the small molecules batefenterol and indacaterol that attenuate the CaM-DDX21 interaction and suppress nascent rRNA synthesis and axon growth in hippocampal neurons. These results unveiled the previously unrecognized role of CaM as a messenger to link the activity-induced Ca2+ influx to the nucleolar events essential for protein synthesis. We thus identified the ability of CaM to transmit information to the nucleoli of neurons in response to stimulation.

A comparative lipid profile of four fish species: From muscle to industrial by-products based on RPLC-Q-TOF-MS/MS.

Fish are crucial for the fishing industry and essential nutrient provision, including lipids. This study employed a high-throughput lipidomic approach to evaluate and contrast the lipid profiles of three marine fish species (P. crocea, S. fuscens, and C. saira) and one freshwater species (H. molitrix) across head, muscle, and viscera. Over 1000 molecular lipid species across 17 subclasses were identified. Notably, acylated monogalactosyldiacylglycerol (acMGDG) was detected for the first time in these species, with a high prevalence of saturated fatty acids (44.7 %-87.7 %). Glycerolipids (67.7 - 86.3 %) and PLs (10.7 - 31.8 %) were identified as the dominant lipid classes. Marine fish muscles displayed higher PL content than freshwater species, and P. crocea viscera contained over 30 % PLs of total lipids. In particular, ether phosphatidyl ethanolamine incorporated more DHA than ether phosphatidylcholine. The viscera of four fish species also exhibited a significant abundance of diacylglycerol (DG), indicating their potential as functional lipid sources. Multivariate analysis identified triglyceride (TG) (59:13), DG (16:1/22:5), and MGDG (16:0/18:2) as potential biomarkers for differentiating among fish anatomical parts. This study deepens the understanding of the nutritional values of these fish, providing guidance for consumer dietary choices and paving the way for transforming previously underutilized by-products into resources with high-value potential.

Hydroxypropyl Cellulose-Based Orally Dissolving Film Loaded with Insoluble Dexamethasone for Treatment of Oral Ulcers.

Oral ulcers present as recurrent and spontaneous lesions, often causing intolerable burning pain that significantly disrupts patients' daily lives and compromises their quality of life. In addressing this clinical challenge, oral dissolving films (ODFs) have emerged as promising pharmaceutical formulations for oral ulcer management due to their rapid onset of action, ease of administration, and portability. In this study, ODFs containing the insoluble drug dexamethasone (Dex) were formulated for the treatment of oral ulcers in rabbits using a solvent casting method with ethanol as the solvent. To optimize the composition of the ODFs, a Box-Behnken Design (BBD) experiment was employed to investigate the effects of varying concentrations of hydroxypropyl cellulose (HPC), low-substituted hydroxypropyl cellulose (L-HPC), and plasticizer (glycerol) on key parameters, such as disintegration time, tensile strength, and peel-off efficiency of the films. Subsequently, the film properties of the Dex-loaded ODFs (ODF@Dex) were thoroughly assessed, revealing favorable attributes, including homogeneity, mechanical strength, and solubility. Notably, the use of ethanol as the solvent in the ODF preparation facilitated the homogeneous distribution of insoluble drugs within the film matrix, thereby enhancing their solubility and dissolution rate. Leveraging the potent pharmacological activity of Dex, ODF@Dex was further evaluated for its efficacy in promoting ulcer healing and mitigating the expression of inflammatory factors both in vitro and in vivo. The findings demonstrated that the ODF@Dex exerted significant antiulcer effects by modulating the PI3K/Akt signaling pathway, thus contributing to ulcer resolution. In conclusion, our study underscores the potential of HPC-based ODFs formulated with ethanol as a solvent as a promising platform for delivering insoluble drugs, offering a viable strategy for the clinical management of oral ulcers.

Comprehensive Lipidomic Analysis of Three Edible Microalgae Species Based on RPLC-Q-TOF-MS/MS.

Microalgae, integral to marine ecosystems for their rich nutrient content, notably lipids and proteins, were investigated by using reversed-phase liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (RPLC-Q-TOF-MS/MS). This study focused on lipid composition in three commonly used microalgae species (Spirulina platensis, Chlorella vulgaris, and Schizochytrium limacinum) for functional food applications. The analysis unveiled more than 700 lipid molecular species, including glycolipids (GLs), phospholipids (PLs), sphingolipids (SLs), glycerolipids, and betaine lipids (BLs). GLs (19.9-64.8%) and glycerolipids (24.1-70.4%) comprised the primary lipid. Some novel lipid content, such as acylated monogalactosyldiacylglycerols (acMGDG) and acylated digalactosyldiacylglycerols (acDGDG), ranged from 0.62 to 9.68%. The analysis revealed substantial GLs, PLs, and glycerolipid variations across microalgae species. Notably, S. platensis and C. vulgaris displayed a predominance of fatty acid (FA) 18:2 and FA 18:3 in GLs, while S. limacinum exhibited a prevalence of FA 16:0, collectively constituting over 60% of the FAs of GLs. In terms of PLs and glycerolipids, S. platensis and C. vulgaris displayed elevated levels of arachidonic acid (AA) and eicosapentaenoic acid (EPA), whereas S. limacinum exhibited a significant presence of docosahexaenoic acid (DHA). Principal component analysis (PCA) revealed MGDG (16:0/18:1), DG (16:0/22:5), Cer (d18:1/20:0), and LPC (16:1) as promising lipid markers for discriminating between these microalgae samples. This study contributes to a comprehensive understanding of lipid profiles in three microalgae species, emphasizing their distinct biochemical characteristics and potentially informing us of their high-value utilization in the food industry.

SDS22 coordinates the assembly of holoenzymes from nascent protein phosphatase-1.

SDS22 forms an inactive complex with nascent protein phosphatase PP1 and Inhibitor-3. SDS22:PP1:Inhibitor-3 is a substrate for the ATPase p97/VCP, which liberates PP1 for binding to canonical regulatory subunits. The exact role of SDS22 in PP1-holoenzyme assembly remains elusive. Here, we show that SDS22 stabilizes nascent PP1. In the absence of SDS22, PP1 is gradually lost, resulting in substrate hyperphosphorylation and a proliferation arrest. Similarly, we identify a female individual with a severe neurodevelopmental disorder bearing an unstable SDS22 mutant, associated with decreased PP1 levels. We furthermore find that SDS22 directly binds to Inhibitor-3 and that this is essential for the stable assembly of SDS22:PP1: Inhibitor-3, the recruitment of p97/VCP, and the extraction of SDS22 during holoenzyme assembly. SDS22 with a disabled Inhibitor-3 binding site co-transfers with PP1 to canonical regulatory subunits, thereby forming non-functional holoenzymes. Our data show that SDS22, through simultaneous interaction with PP1 and Inhibitor-3, integrates the major steps of PP1 holoenzyme assembly.

Susceptibility or resilience to childhood peer abuse can be explained by cortical thickness in brain regions involved in emotional regulation.

Experiencing peer abuse in childhood can damage mental health, but some people exhibit resilience against these negative outcomes. However, it remains uncertain which specific changes in brain structures are associated with this type of resilience. We categorized 217 participants into three groups: resilience group, susceptibility group, and healthy control group, based on their experiences of peer abuse and mental health problems. They underwent MRI scans to measure cortical thickness in various brain regions of the prefrontal cortex. We employed covariance analysis to compare cortical thickness among these groups. Individuals who resilient to anxiety exhibited smaller cortical thickness in the bilateral inferior frontal gyrus (IFG), and with larger thickness in the right medial orbitofrontal cortex (mOFC), while those resilient to stress was associated with smaller thickness in both the bilateral IFG and bilateral middle frontal gyrus (MFG). These findings deepen our understanding of the neural mechanisms underlying resilience and offer insight into improving individual resilience.

Effect of recorded mother's voice on emergence delirium in pediatric patients: a systematic review with meta-analysis

Abstract Objective: Emergence delirium is a common complication in children. Recorded mother's voice, as a non-pharmacological measure, is increasingly used to prevent the emergence of delirium in pediatric patients, but sufficient evidence is still needed to prove its efficacy. Methods: Embase, PubMed, Cochrane Library, Web of Science, CINAHL, and Sinomed databases were searched for randomized controlled trials exploring the efficacy of recorded mother's voice in preventing the emergence of delirium in pediatric patients undergoing general anesthesia. The original data were pooled for the meta-analysis with Review Manager 5.4.1. This study was conducted based on the Cochrane Review Methods. Results: Eight studies with 724 children were included in the analysis. Recorded mother's voice reduced the incidence of emergence delirium when compared with either no voice (RR: 0.45; [95 % CI, 0.34 - 0.61]; p < 0.01; I2 = 7 %) or stranger's voice (RR: 0.51; [95 % CI, 0.28 - 0.91]; p = 0.02; I2 = 38 %) without increasing other untoward reactions. In addition, it shortened the post-anesthesia care unit stay time when compared with no voice (MD = -5.64; [95 % CI, -8.43 to -2.58]; p < 0.01, I2 = 0 %), but not stranger's voice (MD = -1.23; [95 % CI, -3.08 to 0.63]; p = 0.19, I2 = 0 %). It also shortened the extubation time and reduced the incidence of postoperative rescue analgesia. Conclusion: The current analysis indicated that recorded mother's voices could reduce the incidence of emergency delirium, shorten post-anesthesia care unit stay time and extubation time, and decrease the incidence of postoperative rescue analgesia in children.

A taxonomic study of Cheiloneurus Westwood (Hymenoptera, Encyrtidae) from China.

Fourteen species of Cheiloneurus from China are studied. Cheiloneurusguangxiensis Zu, sp. nov., is described as new to science, and C.boldyrevi Trjapitzin & Agekyan, 1978, C.bouceki Anis & Hayat, 2002, C.gonatopodis Perkins, 1906, and C.hadrodorys Anis & Hayat, 2002 are newly recorded from China. A key to Chinese species based on females is also presented.

Restore polder and aquaculture enclosure to the lake: Balancing environmental protection and economic growth for sustainable development.

The restoration of lakes and their buffer zones is crucial for understanding the intricate interplay between human activities and natural ecosystems resulting from the implementation of environmental policies. In this study, we investigated the ecological restoration of shallow lakes and buffer zones in the Yangtze-Huaihe River Basin, specifically focusing on the removal of polder and aquaculture enclosure areas within the lakes. By examining data from eight shallow lakes and their corresponding buffer zones, encompassing lake morphology, water quality parameters, and land use/land cover (LULC) data spanning from 2008 to 2022, which shed light on the complex relationships involved. During the process of restoring polder and aquaculture enclosure areas, we observed a general decrease in the extent of polders and aquaculture enclosures within the lakes. Notably, the removal of aquaculture enclosures had a more pronounced effect (reduction rate of 83.37 %) compared to the withdrawal of polders (reduction rate of 48.76 %). Linear regression analysis revealed a significant decrease in the concentrations of seven water quality parameters, including COD, CODMn, TN, TP, NH3-N, Chl-a, and F, while pH and DO factors exhibit a distinct increasing trend. The results of redundancy analysis and Pearson correlation analysis demonstrated significant correlations between the area of polders and aquaculture enclosures and the changes in lake water quality. Encouragingly, the withdrawal of polders and the removal of aquaculture enclosures had a positive impact on the lake water quality improvement. In contrast, the LULC in the buffer zones of the lakes experienced a gradual decline owing to land degradation, resulting in a reduction in ecosystem service value (ESV). These results offer valuable support for policymakers in their endeavors to restore lake water quality, mitigate the degradation of buffer zones land, and promote the sustainable development of land and water resources.

Prediction of Prostate Cancer Risk Stratification Based on A Nonlinear Transformation Stacking Learning Strategy.

PURPOSE: Prostate cancer (PCa) is an epithelial malignancy that originates in the prostate gland and is generally categorized into low, intermediate, and high-risk groups. The primary diagnostic indicator for PCa is the measurement of serum prostate-specific antigen (PSA) values. However, reliance on PSA levels can result in false positives, leading to unnecessary biopsies and an increased risk of invasive injuries. Therefore, it is imperative to develop an efficient and accurate method for PCa risk stratification. Many recent studies on PCa risk stratification based on clinical data have employed a binary classification, distinguishing between low to intermediate and high risk. In this paper, we propose a novel machine learning (ML) approach utilizing a stacking learning strategy for predicting the tripartite risk stratification of PCa. METHODS: Clinical records, featuring attributes selected using the lasso method, were utilized with 5 ML classifiers. The outputs of these classifiers underwent transformation by various nonlinear transformers and were then concatenated with the lasso-selected features, resulting in a set of new features. A stacking learning strategy, integrating different ML classifiers, was developed based on these new features. RESULTS: Our proposed approach demonstrated superior performance, achieving an accuracy of 0.83 and an area under the receiver operating characteristic curve value of 0.88 in a dataset comprising 197 PCa patients with 42 clinical characteristics. CONCLUSION: This study aimed to improve clinicians' ability to rapidly assess PCa risk stratification while reducing the burden on patients. This was achieved by using artificial intelligence-related technologies as an auxiliary method for diagnosing PCa.

Childhood maltreatment and resting-state network connectivity: The risk-buffering role of positive parenting.

Unraveling the neurobiological foundations of childhood maltreatment is important due to the persistent associations with adverse mental health outcomes. However, the mechanisms through which abuse and neglect disturb resting-state network connectivity remain elusive. Moreover, it remains unclear if positive parenting can mitigate the negative impact of childhood maltreatment on network connectivity. We analyzed a cohort of 194 adolescents and young adults (aged 14-25, 47.42% female) from the Neuroscience in Psychiatry Network (NSPN) to investigate the impact of childhood abuse and neglect on resting-state network connectivity. Specifically, we examined the SAN, DMN, FPN, DAN, and VAN over time. We also explored the moderating role of positive parenting. The results showed that childhood abuse was linked to stronger connectivity within the SAN and VAN, as well as between the DMN-DAN, DMN-VAN, DMN-SAN, SAN-DAN, FPN-DAN, SAN-VAN, and VAN-DAN networks about 18 months later. Positive parenting during childhood buffered the negative impact of childhood abuse on network connectivity. To our knowledge, this is the first study to demonstrate the protective effect of positive parenting on network connectivity following childhood abuse. These findings not only highlight the importance of positive parenting but also lead to a better understanding of the neurobiology and resilience mechanisms of childhood maltreatment.

Incidence of dreaming during ciprofol anesthesia for painless gastroscopy.

BACKGROUND: Dreaming is often reported by patients who undergo propofol-based sedation, but there have not been any studies to date focused on the incidence of dreaming and factors associated therewith following the administration of ciprofol anesthesia in patients undergoing painless gastroscopy. The present study was thus developed with the goal of assessing the incidence of dreaming. METHODS: In total, this study enrolled 200 patients undergoing painless gastroscopy. During the procedure, patients' electroencephalographic Bispectral Index (BIS), blood pressure (BP), heart rate (HR), blood oxygen saturation (SpO2), and PETCO2 were monitored. When their MOAA/S score reached five after the procedure, patients were administered questionnaires including the Brice questionnaire and a five-point Likert Scale, and the content of any recalled dreams was also recorded. RESULTS: Overall, 27.5% of the participants in this study reported dreaming during the procedure, with most having experienced simple, pleasant dreams about everyday life. Identified predictors of dreaming during painless gastroscopy included lower ASA grade, preoperative knowledge of painless examination, a higher frequency of dreams in the month before the procedure, poor sleep quality during the month before the procedure, and shorter awakening time. Dreamers showed significantly lower BIS values at 2 min after endoscope insertion and following endoscope removal, and also showed lower minimum BIS values compared with non-dreamers. CONCLUSIONS: The postoperative dream recall incidence in this study was 27.5% among patients undergoing painless gastroscopy under ciprofol sedation anesthesia.

Effect of subclavian vein diameter combined with perioperative fluid therapy on preventing post-induction hypotension in patients with ASA status I or II.

BACKGROUND: Perioperative hypotension is frequently observed following the initiation of general anesthesia administration, often associated with adverse outcomes. This study assessed the effect of subclavian vein (SCV) diameter combined with perioperative fluid therapy on preventing post-induction hypotension (PIH) in patients with lower ASA status. METHODS: This two-part study included patients aged 18 to 65 years, classified as ASA physical status I or II, and scheduled for elective surgery. The first part (Part I) included 146 adult patients, where maximum SCV diameter (dSCVmax), minimum SCV diameter (dSCVmin), SCV collapsibility index (SCVCI) and SCV variability (SCVvariability) assessed using ultrasound. PIH was determined by reduction in mean arterial pressure (MAP) exceeding 30% from baseline measurement or any instance of MAP < falling below 65 mmHg for ≥ a duration of at least 1 min during the period from induction to 10 min after intubation. Receiver Operating Characteristic (ROC) curve analysis was employed to determine the predictive values of subclavian vein diameter and other relevant parameters. The second part comprised 124 adult patients, where patients with SCV diameter above the optimal cutoff value, as determined in Part I study, received 6 ml/kg of colloid solution within 20 min before induction. The study evaluated the impact of subclavian vein diameter combined with perioperative fluid therapy by comparing the observed incidence of PIH after induction of anesthesia. RESULTS: The areas under the curves (with 95% confidence intervals) for SCVCI and SCVvariability were both 0.819 (0.744-0.893). The optimal cutoff values were determined to be 45.4% and 14.7% (with sensitivity of 76.1% and specificity of 86.7%), respectively. Logistic regression analysis, after adjusting for confounding factors, demonstrated that both SCVCI and SCVvariability were significant predictors of PIH. A threshold of 45.4% for SCVCI was chosen as the grouping criterion. The incidence of PIH in patients receiving fluid therapy was significantly lower in the SCVCI ≥ 45.4% group compared to the SCVCI < 45.4% group. CONCLUSIONS: Both SCVCI and SCVvariability are noninvasive parameters capable of predicting PIH, and their combination with perioperative fluid therapy can reduce the incidence of PIH.

Identification of benzo[b]thiophene-1,1-dioxide derivatives as novel PHGDH covalent inhibitors.

The increased de novo serine biosynthesis confers many advantages for tumorigenesis and metastasis. Phosphoglycerate dehydrogenase (PHGDH), a rate-limiting enzyme in serine biogenesis, exhibits hyperactivity across multiple tumors and emerges as a promising target for cancer treatment. Through screening our in-house compound library, we identified compound Stattic as a potent PHGDH inhibitor (IC50 = 1.98 ± 0.66 µM). Subsequent exploration in structural activity relationships led to the discovery of compound B12 that demonstrated the increased enzymatic inhibitory activity (IC50 = 0.29 ± 0.02 µM). Furthermore, B12 exhibited robust inhibitory effects on the proliferation of MDA-MB-468, NCI-H1975, HT1080 and PC9 cells that overexpress PHGDH. Additionally, using a [U-13C6]-glucose tracing assay, B12 was found to reduce the production of glucose-derived serine in MDA-MB-468 cells. Finally, mass spectrometry-based peptide profiling, mutagenesis experiment and molecular docking study collectively suggested that B12 formed a covalent bond with Cys421 of PHGDH.