ncRNADrug: a database for validated and predicted ncRNAs associated with drug resistance and targeted by drugs.

Drug resistance is a major barrier in cancer treatment and anticancer drug development. Growing evidence indicates that non-coding RNAs (ncRNAs), especially microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), play pivotal roles in cancer progression, therapy, and drug resistance. Furthermore, ncRNAs have been proven to be promising novel therapeutic targets for cancer treatment. Reversing dysregulated ncRNAs by drugs holds significant potential as an effective therapeutic strategy for overcoming drug resistance. Therefore, we developed ncRNADrug, an integrated and comprehensive resource that records manually curated and computationally predicted ncRNAs associated with drug resistance, ncRNAs targeted by drugs, as well as potential drug combinations for the treatment of resistant cancer. Currently, ncRNADrug collects 29 551 experimentally validated entries involving 9195 ncRNAs (2248 miRNAs, 4145 lncRNAs and 2802 circRNAs) associated with the drug resistance of 266 drugs, and 32 969 entries involving 10 480 ncRNAs (4338 miRNAs, 6087 lncRNAs and 55 circRNAs) targeted by 965 drugs. In addition, ncRNADrug also contains associations between ncRNAs and drugs predicted from ncRNA expression profiles by differential expression analysis. Altogether, ncRNADrug surpasses the existing related databases in both data volume and functionality. It will be a useful resource for drug development and cancer treatment. ncRNADrug is available at http://www.jianglab.cn/ncRNADrug.

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.

Trp207 regulation of voltage-dependent activation of human Hv1 proton channel.

In voltage-gated Na+ and K+ channels, the hydrophobicity of noncharged residues in the S4 helix has been shown to regulate the S4 movement underlying the process of voltage-sensing domain (VSD) activation. In voltage-gated proton channel Hv1, there is a bulky noncharged tryptophan residue located at the S4 transmembrane segment. This tryptophan remains entirely conserved across all Hv1 members but is not seen in other voltage-gated ion channels, indicating that the tryptophan contributes different roles in VSD activation. The conserved tryptophan of human voltage-gated proton channel Hv1 is Trp207 (W207). Here, we showed that W207 modifies human Hv1 voltage-dependent activation, and small residues replacement at position 207 strongly perturbs Hv1 channel opening and closing, and the size of the side chain instead of the hydrophobic group of W207 regulates the transition between closed and open states of the channel. We conclude that the large side chain of tryptophan controls the energy barrier during the Hv1 VSD transition.

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.

Abnormalities in brain structure following childhood unpredictability: a mechanism underlying depressive and anxiety symptoms.

BACKGROUND: Childhood adversity is associated with abnormalities in brain structure, but this association has not been tested for childhood unpredictability, one form of adversity. We studied whether abnormalities in gray matter volume (GMV) could be a mechanism linking childhood unpredictability and psychopathology, over and above the effect of childhood trauma. METHODS: Participants were 158 right-handed healthy young adults (aged 17-28 years, M = 22.07, s.d. = 2.08; 66.46% female) who underwent structural magnetic resonance imaging measurements and provided retrospective reports of childhood unpredictability. The anxiety and depression subscales of the self-report Brief Symptom Inventory-53 were used to index psychopathology. RESULTS: Whole-brain voxel-based morphometric analyses showed that after controlling for the effect of childhood trauma, childhood unpredictability was correlated with greater GMV in bilateral frontal pole, bilateral precuneus, bilateral postcentral gyrus, right hemisphere of fusiform, and lingual gyrus, and left hemisphere of ventrolateral prefrontal cortex as well as occipital gyrus. Greater GMV in bilateral frontal pole, bilateral precuneus, and bilateral postcentral gyrus mediated associations between unpredictability and symptoms of depression and anxiety. CONCLUSIONS: The findings suggest that childhood unpredictability could exact unique effects on neural development, over and above the effect of childhood trauma. These findings are relevant for understanding the occurrence of psychopathology following childhood unpredictability and have implications for intervention.

Neutrophil-Based Bionic Delivery System Breaks Through the Capillary Barrier of Liver Sinusoidal Endothelial Cells and Inhibits the Activation of Hepatic Stellate Cells.

The capillarization of hepatic sinusoids resulting from the activation of hepatic stellate cells poses a significant challenge, impeding the effective delivery of therapeutic agents to the Disse space for liver fibrosis treatment. Therefore, overcoming these barriers and achieving efficient drug delivery to activated hepatic stellate cells (aHSCs) are pressing challenge. In this study, we developed a synergistic sequential drug delivery approach utilizing neutrophil membrane hybrid liposome@atorvastatin/amlisentan (NCM@AtAm) and vitamin A-neutrophil membrane hybrid liposome @albumin (VNCM@Bai) nanoparticles (NPs) to breach the capillary barrier for targeted HSC cell delivery. Initially, NCM@AtAm NPs were successfully directed to the site of hepatic fibrosis through neutrophil-mediated inflammatory targeting, resulting in the normalization of liver sinusoidal endothelial cells (LSECs) and restoration of fenestrations under the combined influence of At and Am. Elevated tissue levels of the p-Akt protein and endothelial nitric oxide synthase (eNOS) indicated the normalization of LSECs following treatment with At and Am. Subsequently, VNCM@Bai NPs traversed the restored LSEC fenestrations to access the Disse space, facilitating the delivery of Bai into aHSCs under vitamin A guidance. Lastly, both in vitro and in vivo results demonstrated the efficacy of Bai in inhibiting HSC cell activation by modulating the PPAR γ/TGF-ß1 and STAT1/Smad7 signaling pathways, thereby effectively treating liver fibrosis. Overall, our designed synergistic sequential delivery system effectively overcomes the barrier imposed by LSECs, offering a promising therapeutic strategy for liver fibrosis treatment in clinical settings.

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.

Dimethyl fumarate attenuates cholestatic liver injury by activating the NRF2 and FXR pathways and suppressing NLRP3/GSDMD signaling in mice.

The progression of cholestasis is characterized by excessive accumulation of bile acids (BAs) in the liver, which leads to oxidative stress (OS), inflammation and liver injury. There are currently limited treatments for cholestasis. Therefore, appropriate drugs for cholestasis treatment need to be developed. Dimethyl fumarate (DMF) has been widely used in the treatment of various diseases and exerts antioxidant and anti-inflammatory effects, but its effect on cholestatic liver disease remains unclarified. We fed mice 3,5-diethoxycarbonyl-1,4-dihydrocollidine or cholic acid to induce cholestatic liver injury and treated these mice with DMF to evaluate its protective ability. Alanine aminotransferase, aspartate aminotransferase, and total liver BAs were assessed as indicators of liver function. The levels of OS, liver inflammation, transporters and metabolic enzymes were also measured. DMF markedly altered the relative ALT and AST levels and enhanced the liver antioxidant capacity. DMF regulated the MST/NRF2 signaling pathway to protect against OS and reduced liver inflammation through the NLRP3/GSDMD signaling pathway. DMF also regulated the levels of BA transporters by promoting FXR protein expression. These findings provide new strategies for the treatment of cholestatic liver disorders.

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.

Exploring the association between early exposure to material hardship and psychopathology through indirect effects of fronto-limbic functional connectivity during fear learning.

Experiencing family material hardship has been shown to be associated with disruptions in physical and psychological development. However, the association between material hardship and functional connectivity in the fronto-limbic circuit during fear learning is unclear. A total of 161 healthy young adults aged 17-28 were recruited in our brain imaging study, using the Fear Conditioning Task to test the associations between material hardship and connectivity in fronto-limbic circuit and psychopathology. The results showed that family material hardship was linked to higher positive connectivity between the left amygdala and bilateral dorsal anterior cingulate cortex, as well as higher negative connectivity between the left hippocampus and right ventromedial prefrontal cortex. A mediation analysis showed that material hardship was associated with depression via amygdala functional connectivity (indirect effect = 0.228, P = 0.016), and also indirectly associated with aggression and anger-hostility symptoms through hippocampal connections (aggression: indirect effect = 0.057, P = 0.001; anger-hostility: indirect effect = 0.169, P = 0.048). That is, family material hardship appears to affect fronto-limbic circuits through changes in specific connectivity, and these specific changes, in turn, could lead to specific psychological symptoms. The findings have implications for designing developmentally sensitive interventions to mitigate the emergence of psychopathological symptoms.

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.

The effect of different endotracheal tube cuff pressure monitoring systems on postoperative sore throat in patients undergoing tracheal intubation: a randomized clinical trial.

BACKGROUND: Postoperative sore throat (POST) is an unpleasant outcome that can occur as a result of tracheal intubation in adults. Increased pressure from the endotracheal tube (ETT) cuff often leads to local mucosal injury, resulting in sore throat. The purpose of this study was to compare the effect of two different ETT cuff pressure monitoring systems vs. no cuff pressure monitoring on the incidence and severity of POST in adults. METHODS: One hundred and fourteen ASA I-III patients of either gender, aged 18-65 years, and undergoing surgery requiring endotracheal intubation were included in this study. Patients were randomized into three groups: control (C), cuff pressure gauge (G), and automated cuff controller (A). The ETT cuff pressure was not monitored intraoperatively in group C but was monitored using a cuff pressure gauge and an automated cuff controller in groups G and A, respectively. Postoperatively, patients were assessed at 2, 24, and 48 h for the presence and severity of POST, hoarseness and cough. RESULTS: One hundred and eleven patients completed the study. POST occurred in 40.5% of the patients in group G (n = 37) (p = 0.013) and 23.7% of the patients in group A (n = 38) (p < 0.001) within 48 h after surgery, compared to 69.4% in group C (n = 36). There were no significant differences in hoarseness, coughing, and dysphagia across the groups at any time. When comparing groups A and C, individuals in group A exhibited a lower occurrence of significant (grade ≥ 2) POST and hoarseness (10.5% vs. 41.7%, p = 0.002; 26.3% vs. 58.3%, p = 0.005). The incidence of significant cough and dysphagia did not differ substantially across the patient groups within 48 h after surgery. POST scores in group A at 2, 24 h postoperatively were both 0 (0-0), which was significantly lower than those in group C (1 (0-2) at 2 h, p < 0.001 ; 1 (0-1) at 24 h, p = 0.001). POST in group G at 2 h postoperatively was graded as 0 (0-1.5) which was milder than group C (P = 0.024). The severity of hoarseness in group A with scores of 0 (0-2) was superior to that in group C (2 (0-2), p = 0.006) at 2 h postoperatively. CONCLUSIONS: In conclusion, the findings of this study indicated that the occurrence of POST can be reduced by using either the cuff pressure gauge approach or the automated cuff controller method. The automated cuff controller monitoring can potentially decrease the severity of POST and hoarseness. TRIAL REGISTRATION: Chinese Clinical Trial Registry, identifier: ChiCTR2100054089, Date: 08/12/2021.

The effect of haloperidol's perioperative application on postoperative delirium in elderly patients: a systematic review and meta-analysis.

OBJECTIVES: To systematically review the evidence about the effect of haloperidol on postoperative delirium in elderly patients. METHODS: PubMed, Embase, the Cochrane Library and China National Knowledge Infrastructure were used to find concerned studies for meta-analysis. The main outcome was the incidence of postoperative delirium, and the secondary outcomes were side effects of haloperidol and the length of hospital stay. The meta-analyses were conducted using the Review Manager Version 5.1. This study was conducted based on the PRISMA statement. RESULTS: Eight RCTs (1569 patients) were included in the meta-analysis. There was a significant difference in the incidence of postoperative delirium between haloperidol and control groups (OR = 0.62, 95%CI 0.48-0.80, P = 0.0002, I2 = 20%). In addition, side effects of haloperidol and the duration of hospitalization were comparable (OR = 0.58, 95%CI 0.25-1.35, P = 0.21, I2 = 0%; MD =-0.01, 95%CI -0.16-0.15, P = 0.92, I2 = 28%). Subgroup analysis implied the effect of haloperidol on postoperative delirium might vary with the dose (5 mg daily: OR = 0.40, 95%CI 0.22-0.71, P = 0.002, I2 = 0%; <5 mg daily: OR = 0.72, 95%CI 0.42-1.23, P = 0.23, I2 = 0%). CONCLUSIONS: The meta-analysis revealed perioperative application of haloperidol could decrease the occurrence of postoperative delirium without obvious side effects in elderly people, and high-dose haloperidol (5 mg daily) possessed a greater positive effect.

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.

An Improved Instance Segmentation Method for Complex Elements of Farm UAV Aerial Survey Images.

Farm aerial survey layers can assist in unmanned farm operations, such as planning paths and early warnings. To address the inefficiencies and high costs associated with traditional layer construction, this study proposes a high-precision instance segmentation algorithm based on SparseInst. Considering the structural characteristics of farm elements, this study introduces a multi-scale attention module (MSA) that leverages the properties of atrous convolution to expand the sensory field. It enhances spatial and channel feature weights, effectively improving segmentation accuracy for large-scale and complex targets in the farm through three parallel dense connections. A bottom-up aggregation path is added to the feature pyramid fusion network, enhancing the model's ability to perceive complex targets such as mechanized trails in farms. Coordinate attention blocks (CAs) are incorporated into the neck to capture richer contextual semantic information, enhancing farm aerial imagery scene recognition accuracy. To assess the proposed method, we compare it against existing mainstream object segmentation models, including the Mask R-CNN, Cascade-Mask, SOLOv2, and Condinst algorithms. The experimental results show that the improved model proposed in this study can be adapted to segment various complex targets in farms. The accuracy of the improved SparseInst model greatly exceeds that of Mask R-CNN and Cascade-Mask and is 10.8 and 12.8 percentage points better than the average accuracy of SOLOv2 and Condinst, respectively, with the smallest number of model parameters. The results show that the model can be used for real-time segmentation of targets under complex farm conditions.

The epigenetic regulatory mechanism of PIWI/piRNAs in human cancers.

PIWI proteins have a strong correlation with PIWI-interacting RNAs (piRNAs), which are significant in development and reproduction of organisms. Recently, emerging evidences have indicated that apart from the reproductive function, PIWI/piRNAs with abnormal expression, also involve greatly in varieties of human cancers. Moreover, human PIWI proteins are usually expressed only in germ cells and hardly in somatic cells, so the abnormal expression of PIWI proteins in different types of cancer offer a promising opportunity for precision medicine. In this review, we discussed current researches about the biogenesis of piRNA, its epigenetic regulatory mechanisms in human cancers, such as N6-methyladenosine (m6A) methylation, histone modifications, DNA methylation and RNA interference, providing novel insights into the markers for clinical diagnosis, treatment and prognosis in human cancers.

Development and validation of a clinic machine-learning nomogram for the prediction of risk stratifications of prostate cancer based on functional subsets of peripheral lymphocyte.

BACKGROUND: Non-invasive risk stratification contributes to the precise treatment of prostate cancer (PCa). In previous studies, lymphocyte subsets were used to differentiate between low-/intermediate-risk and high-risk PCa, with limited clinical value and poor interpretability. Based on functional subsets of peripheral lymphocyte with the largest sample size to date, this study aims to construct an easy-to-use and robust nomogram to guide the tripartite risk stratifications for PCa. METHODS: We retrospectively collected data from 2039 PCa and benign prostate disease (BPD) patients with 42 clinical characteristics on functional subsets of peripheral lymphocyte. After quality control and feature selection, clinical data with the optimal feature subset were utilized for the 10-fold cross-validation of five Machine Learning (ML) models for the task of predicting low-, intermediate- and high-risk stratification of PCa. Then, a novel clinic-ML nomogram was constructed using probabilistic predictions of the trained ML models via the combination of a multivariable Ordinal Logistic Regression analysis and the proposed feature mapping algorithm. RESULTS: 197 PCa patients, including 56 BPD, were enrolled in the study. An optimal subset with nine clinical features was selected. Compared with the best ML model and the clinic nomogram, the clinic-ML nomogram achieved the superior performance with a sensitivity of 0.713 (95% CI 0.573-0.853), specificity of 0.869 (95% CI 0.764-0.974), F1 of 0.699 (95% CI 0.557-0.841), and AUC of 0.864 (95% CI 0.794-0.935). The calibration curve and Decision Curve Analysis (DCA) indicated the predictive capacity and net benefits of the clinic-ML nomogram were improved. CONCLUSION: Combining the interpretability and simplicity of a nomogram with the efficacy and robustness of ML models, the proposed clinic-ML nomogram can serve as an insight tool for preoperative assessment of PCa risk stratifications, and could provide essential information for the individual diagnosis and treatment in PCa patients.

Polyaspartic Acid-Stabilized CaCO3-Containing In Situ Hydrogel for Protection and Treatment of Gastric Ulcer.

The lack of effective oral drug delivery systems to treat gastric ulcer is an urgent challenge in clinical practice. Herein, a gastric acid pH-responsive hydrogel of curcumin/sodium alginate/polyaspartic acid@CaCO3 (Cur/SA/PC) was developed for sustained release of Cur, exerting effective protection and treatment of gastric ulcers. The in vitro gelatinization properties and the corresponding gel characteristics of the SA/PC delivery system demonstrated the successful construction of the in situ hydrogel with uniform strength. The cellular uptake illustrated the successful uptake and sustained release of Cur. Besides, Cur effectively inhibited NLRP3-mediated pyroptosis both in vitro and in vivo, exhibited an excellent pro-healing effect by regulating the PI3K/Akt signaling pathway, and alleviated acetic acid-induced chronic gastric injury in rats. Moreover, the relative bioavailability of Cur in the SA/PC hydrogel could effectively increase in the pharmacokinetic study. Importantly, the protective barrier formed by the SA/PC hydrogel could effectively protect against alcohol-induced acute gastric ulcers in rats. Overall, the designed SA/PC oral delivery system is a promising strategy to overcome gastric barriers for oral drug delivery.

Metabolomics identify landscape of food sensory properties.

Sensory evaluation is a key component of food production strategy. The classical food sensory evaluation method is time-consuming, laborious, costly, and highly subjective. Since flavor (taste and smell), texture, and mouthfeel are all related to the chemical properties of food, there has been a growing interest in how they affect the senses of food. In the past decades, emerging metabolomics has received much attention in the field of sensory evaluation, because it not only offers a broad picture of chemical composition for sensory properties but also revealed their changes and functions in food proceeding. This article reviewed food chemicals regarding the flavor, smell, and texture of foods, and discussed the advantages and limitations of applying metabolomics approaches to sensory evaluation, including GC-MS, LC-MS, and NMR. Taken together, this review gives a comprehensive, critical overview of the current state, future challenges, and trends in metabolomics on food sensory properties.

Effects of continuous and slow tracheal tube cuff deflation on cough reflex during extubation in noncardiac surgery patients: a randomised clinical trial.

BACKGROUND: The incidence of cough reflex during extubation is 76%. Cough reflex causes severe hemodynamic fluctuations and airway complications. This prospective trial investigated the potential effects of tracheal tube cuff deflation on cough reflex during extubation. METHODS: One hundred and twenty-six patients scheduled for operations within 3 h under general anaesthesia with orotracheal intubation were randomly assigned to one of three groups: control (C), experimental (E) or syringe (S) groups. Patients in group C underwent tracheal tube cuff deflation using a 10-ml syringe in 1 s, patients in group E underwent tracheal tube cuff deflation continuously and slowly in 5 s using a cuff pressure gauge until the pressure was zero and patients in group S underwent tracheal tube cuff deflation using a 10-ml syringe at a speed of 1 ml s-1. The incidence and severity of cough reflexs during extubation and the incidence of postoperative airway complications within 48 h were assessed. RESULTS: Compared with group C (60.0%), the incidence of cough reflex in group E was 9.8% (p < 0.001) and in group S was 12.5% (p < 0.001). The severity of cough reflex was graded as 2 (1-2) in group C, 1 (1-1) in group E and 1 (1-1) in group S (p < 0.001 for group comparisons). The incidence of hoarseness in group C was 0.0%, in group E was 19.5% and in group S was 5.0% (p < 0.05 for all groups, p = 0.009 between group C and E). CONCLUSIONS: Compared with deflating a trachal tube cuff with a 10-ml syringe in 1 s, the use of a 10-ml syringe at a speed of 1 ml s-1 or a cuff pressure guage within 5 s can both reduce the incidence of cough reflex, but deflating with a cuff pressure guage can increase the incidence of postoperative hoarseness. TRIAL REGISTRATION: Chinese Clinical Trial Registry, identifier: ChiCTR2100054089, Date: 08/12/2021.