Self-Illuminating Copper-Luminol Coordination Polymers for Bioluminescence Imaging of Oxidative Damage.

Timely detection of reactive oxygen species (ROS) accumulated during inflammation is essential for an early disease diagnosis. Compared to fluorescence probes with limited sensitivity and accuracy, chemiluminescence (CL) imaging offers the potential for highly sensitive molecular visualization of ROS by minimizing background interferences. However, the development of bright and easily manufacturable CL probes for ROS imaging remains challenging. In this study, a novel chemiluminescent nanoprobe named Cu-Lum@NPs for ROS imaging in inflammation was synthesized by using a one-step solvothermal method. The Cu-Lum@NPs, which are composed of coordination polymers containing copper ions and luminol (Lum), demonstrate intrinsic peroxidase-like activity that relies on Cu(I) as the catalytic active center to initiate the Fenton reaction. This catalytic process facilitates the decomposition of hydrogen peroxide (H2O2) into hydroxyl radicals (•OH) and superoxide anion radicals (O2•-), leading to the oxidation of Lum and inducing strong luminescence. Cu-Lum@NPs, displaying nanozyme characteristics, were observed to accelerate and enhance the ROS-responsive luminescence (10-1600-fold in solution and over 100-fold in neutrophils) and notably extend persistent luminescence. The Cu-Lum@NPs allowed for CL imaging of endogenous ROS in living cells and animals with an outstanding signal-to-noise ratio exceeding 96 and facilitated oxidative damage luminescence imaging for tissue-specific detection. The study presents Cu-Lum@NPs, a highly sensitive and easily manufacturable chemiluminescent nanoprobe for ROS imaging both in vitro and in vivo, exhibiting enhanced luminescence and prolonged persistence for ROS-related disease detection.

A target-triggered colorimetric sensor for ultrasensitive detection of miRNAs based on self-powered three-dimensional DNA walker.

MicroRNAs (miRNAs) play an important role in the process of heart failure (HF) and are emerging biomarkers that can be used for the auxiliary diagnosis of HF. However, it is very challenging to accurately analyze the expression levels of trace miRNAs in complex clinical samples. Here, we developed an enzyme-free colorimetric sensor for the ultrasensitive detection of miRNA-423-5p (HF-associated miRNA) based on three-dimensional DNA walkers constructed from functional nucleic acids and gold nanoparticles (AuNPs). DNAzyme with cleavage activity was specifically activated by miRNA-423-5p to sustainably cleave the substrate, thereby releasing the trigger sequence to initiate the subsequent mismatched catalytic hairpin assembly (MCHA) cycle. Then, as the MCHA cycle proceeded to continuously expose the G-quadruplex (GQ) sequence, the sequence bound with hemin to form a large amount of GQ/hemin DNAzyme on the surface of the AuNPs, which rapidly catalyzed the chromogenic oxidation of 3,3',5,5'-tetramethylbenzidine to yield an amplified colorimetric signal readout. The colorimetric sensor exhibited an ultralow detection limit (32 fM), showed excellent specificity and performed well in serum samples. The sensor was applied to detect miRNA-423-5p in clinical plasma samples from healthy individuals and HF patients, and the results revealed its good clinical application in HF diagnosis. Thus, the developed colorimetric sensor provides a convenient detection tool for early screening and diagnosis of HF, as well as for pathophysiological studies.

Head-neck local ventilation mode for long-narrow mine working face.

To improve the thermal health state of workers in mines facing heat hazards and enhance cooling capacity utilization efficiency of mine ventilation, this study proposes a suitable air distribution for mine workers' local cooling, taking into account the characteristics of long-narrow underground space and workers. The suggested air distribution involves harnessing underground cold air jets along with the mine's crossflow (mainstream ventilation) to create a localized safeguard airflow around the worker's head-neck, known as jet ventilation in crossflow (JVIC). The flow visualization experiment identified five flow patterns within a confined space. The study explores the impact of the velocity ratio (R) and confinement scale (C) on the evolution of JVIC flow patterns and presents a parametric description of the resulting flow field. Drawing on the microclimate control scope around mine workers' head-neck, the study defines the effective cooling zone and the ineffective cooling zone as the boundaries for controlling JVIC air distribution within confined mine spaces. This clarifies the applicability of the air distribution form and introduces an evaluation model for assessing the cooling effect and the efficiency of cooling capacity utilization to manage the non-uniform underground environment.

Phillyrin and its metabolites exert antipyretic effects by targeting the NAD+ binding domain of GAPDH, MDH2 and IDH2.

BACKGROUND: Fever is one of the main pathophysiological reactions that occurs during the acute phase of various diseases. Excessive body temperature can lead to various adverse consequences such as brain tissue damage and abnormal immune responses. Phillyrin (Phr) is the main active ingredient in Forsythia suspensa (Thunb.) Vahl (Lian Qiao) and has antipyretic effects; however, its antipyretic mechanism of action remains unclear. PURPOSE: This study aimed to explore the antipyretic mechanisms of Phr and provide a new treatment plan for fever. METHODS: The antipyretic effects of Phr were evaluated using a mouse model of pneumonia fever. The main metabolites of Phr involved in its antipyretic function were identified using a mitochondrial temperature-sensitive probe. Further synthesis of the main metabolite, phillygenin (Phg), an alkynylated probe, was performed, and chemical proteomics was used to capture and analyze its direct target for antipyretic effects. The mechanism of action of Phg and its antipyretic targets was explored using metabolomics and various molecular biology methods. RESULTS: Phr showed significant antipyretic and anti-inflammatory effects in a mouse model of lipopolysaccharide-induced fever. Phg reversibly targeted the nicotinamide adenine dinucleotide (NAD+) binding domain of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), malate dehydrogenase 2 (MDH2), and isocitrate dehydrogenase 2 (IDH2) to inhibit their enzymatic activity. In-depth analysis of cellular metabolomics and mitochondrial stress testing indicated that inhibition of GAPDH, MDH2, and IDH2 enzyme activity by Phg led to a decrease in cellular energy supply and heat production regulated by glycolysis, tricarboxylic acid cycle, and oxidative phosphorylation signaling pathways. Phg specifically targeted macrophages and inhibited LPS-induced macrophage activation by downregulating GAPDH enzyme activity, thereby exerting anti-inflammatory effects. In vivo experiments also confirmed that the antipyretic effect of Phr in LPS-induced fever model mice was related to its main metabolites, Phg and Phg-sulfonate (Phg-S), which directly targeted the NAD+ binding domain of GAPDH, IDH2, and MDH2, inhibiting the activity of these enzymes, thereby reducing energy supply and regulating febrile-related inflammatory factors. CONCLUSION: This study reported for the first time that the antipyretic effect of Phr is produced by targeting GAPDH, IDH2, and MDH2 to regulate energy supply and febrile-related inflammatory factors through its main metabolites Phg and Phg-S. This study not only provides potential drugs for fever treatment but also provides new ideas for improving clinical fever treatment plans.

Predictive value of preoperative ultrasonographic measurement of gastric morphology for the occurrence of postoperative nausea and vomiting among patients undergoing gynecological laparoscopic surgery.

Background: Pre-operative prediction of postoperative nausea and vomiting (PONV) is primarily based on the patient's medical history. The predictive value of gastric morphological parameters observed on ultrasonography has not been comprehensively assessed. Methods: A prospective observational study was conducted to evaluate the pre-operative ultrasonographic measurement of gastric morphology for predicting PONV. The gastric antrum of the participants was assessed using ultrasound before anesthesia, and the occurrence of PONV in the first 6 hours and during the 6-24 hours after surgery was reported. The main indicators included the thickness of the muscularis propria (TMP) and the cross-sectional area of the inner side of the muscularis propria (CSA-ISMP). These were recorded and analyzed. Logistic regression analysis was applied to identify factors for PONV. Results: A total of 72 patients scheduled for elective gynecological laparoscopic surgery were investigated in the study. The pre-operative CSA-ISMP of patients with PONV in the first 6 hours was significantly greater than that of those without PONV (2.765 ± 0.865 cm² vs 2.349 ± 0.881 cm², P=0.0308), with an area under the curve of 0.648 (95% CI, 0.518 to 0.778, P=0.031). Conversely, the pre-operative TMP of patients with PONV during the 6-24 hours was significantly smaller than that of those without PONV (1.530 ± 0.473 mm vs 2.038 ± 0.707 mm, P=0.0021), with an area under the curve of 0.722 (95% CI, 0.602 to 0.842, P=0.003). Logistic regression analysis confirmed that CSA-ISMP was an independent risk factor for PONV in the first 6 hours (OR=2.986, P=0.038), and TMP was an independent protective factor for PONV during the 6-24 hours after surgery (OR=0.115, P=0.006). Conclusion: Patients with a larger pre-operative CSA-ISMP or a thinner TMP are prone to develop PONV in the first 6 hours or during the 6-24 hours after surgery, respectively. China clinical trial registration center: http://www.chictr.org.cn (ChiCTR2100055068).

Research on the technology of uniformly injecting nitrogen into the porous long pipes in the gob of the gob-side entry retaining mining mode with roof cutting and pressure relief.

The implementation of the Gob-Side Entry Retaining Mining Mode with Roof Cutting and Pressure Relief (GERRCPR) results in the gob connecting to the retaining roadway, creating an open space that causes significant air leakage and increases the risk of spontaneous combustion. A study was conducted during the implementation of the GERRCPR in the Xiaonan Coal Mine N1-1502 working face to investigate spontaneous combustion characteristics, along with fire prevention and extinguishing measures. To analyze gob airflow, Computational Fluid Dynamics (CFD) was employed to collect data on airflow conditions, O2 concentration, and temperature. Based on this, this study focuses on exploring the effects of nitrogen injection treatment under various rates and positions to optimize parameters for buried pipe nitrogen injection. Results indicated that within the GERRCPR, air leakage in the gob increased, leading to an increase in O2 concentration, expansion of the oxidation zone, and an elevated risk of spontaneous combustion. Air leakage primarily occurred from the retaining roadway and the working face near the intake-air roadway, peaking at a retaining roadway length of 500 m, with a flow rate of 226 m3/min. Following nitrogen injection treatment, the oxidation zone was significantly reduced, with optimal treatment achieved at a nitrogen injection depth of 70 m and a rate of 600 m3/h. Field monitoring data showed that the inertization measure of using porous long pipes, a nitrogen injection spacing of 30 m, and a nitrogen injection rate of 600 m3/h significantly decreased the O2 concentration within the gob. This reduction meets safety production requirements and outperforms the effectiveness of traditional buried-pipe nitrogen injection methods, thereby validating the simulation accuracy. Understanding the laws governing spontaneous coal combustion in the GERRCPR and enacting preventive measures for nitrogen injection can improve safety standards in mining operations. This proactive approach can effectively prevent spontaneous coal combustion accidents, resulting in substantial social benefits.

Branched-chain amino acid transaminase 1 confers EGFR-TKI resistance through epigenetic glycolytic activation.

Third-generation EGFR tyrosine kinase inhibitors (TKIs), exemplified by osimertinib, have demonstrated promising clinical efficacy in the treatment of non-small cell lung cancer (NSCLC). Our previous work has identified ASK120067 as a novel third-generation EGFR TKI with remarkable antitumor effects that has undergone New Drug Application (NDA) submission in China. Despite substantial progress, acquired resistance to EGFR-TKIs remains a significant challenge, impeding the long-term effectiveness of therapeutic approaches. In this study, we conducted a comprehensive investigation utilizing high-throughput proteomics analysis on established TKI-resistant tumor models, and found a notable upregulation of branched-chain amino acid transaminase 1 (BCAT1) expression in both osimertinib- and ASK120067-resistant tumors compared with the parental TKI-sensitive NSCLC tumors. Genetic depletion or pharmacological inhibition of BCAT1 impaired the growth of resistant cells and partially re-sensitized tumor cells to EGFR TKIs. Mechanistically, upregulated BCAT1 in resistant cells reprogrammed branched-chain amino acid (BCAA) metabolism and promoted alpha ketoglutarate (α-KG)-dependent demethylation of lysine 27 on histone H3 (H3K27) and subsequent transcriptional derepression of glycolysis-related genes, thereby enhancing glycolysis and promoting tumor progression. Moreover, we identified WQQ-345 as a novel BCAT1 inhibitor exhibiting antitumor activity both in vitro and in vivo against TKI-resistant lung cancer with high BCAT1 expression. In summary, our study highlighted the crucial role of BCAT1 in mediating resistance to third-generation EGFR-TKIs through epigenetic activation of glycolysis in NSCLC, thereby supporting BCAT1 as a promising therapeutic target for the treatment of TKI-resistant NSCLC.

Ethnopharmacology, phytochemistry, pharmacology and product application of Platycodon grandiflorum: A review.

Platycodonis Radix (Jiegeng in Chinese) is a well-known traditional Chinese medicine used for both medicinal and culinary purposes. Its historical use as an antitussive and expectorant has been extensively documented. Researchers, to date, have identified 219 chemical constituents in Platycodon grandiflorum (Jacq.) A. DC, encompassing 89 saponins, 11 flavonoids, 21 polysaccharides, 14 phenolic acids, six polyacetylenes, five sterols, 34 fatty acids, 17 amino acids, and 22 trace elements. Jiegeng exhibits diverse pharmacological effects, including antitussive and anti-phlegm properties, anti-cancer activity, anti-inflammatory effects, immune regulation, antioxidant properties, anti-obesity, and antidiabetic effects. Additionally, Jiegeng shows potential in protecting the heart and liver. Beyond its medicinal benefits, Jiegeng is highly esteemed in culinary applications, and its global demand is on the rise. Its utilization has expanded beyond medicine and food to encompass daily necessities, cosmetics, agricultural supplies, and other fields. Currently, there are 18 272 patents related to P. grandiflorum. This comprehensive review summarizes the latest research published over the past 20 years, providing a robust foundation for further exploration of the medicinal and health benefits of P. grandiflorum.

Research on the Mechanism and Material Basis of Corn (Zea mays L.) Waste Regulating Dyslipidemia.

Corn (Zea mays L.) is an essential gramineous food crop. Traditionally, corn wastes have primarily been used in feed, harmless processing, and industrial applications. Except for corn silk, these wastes have had limited medicinal uses. However, in recent years, scholars have increasingly studied the medicinal value of corn wastes, including corn silk, bracts, husks, stalks, leaves, and cobs. Hyperlipidemia, characterized by abnormal lipid and/or lipoprotein levels in the blood, is the most common form of dyslipidemia today. It is a significant risk factor for atherosclerosis and can lead to cardiovascular and cerebrovascular diseases if severe. According to the authors' literature survey, corn wastes play a promising role in regulating glucose and lipid metabolism. This article reviews the mechanisms and material basis of six different corn wastes in regulating dyslipidemia, aiming to provide a foundation for the research and development of these substances.

Tetrandrine inhibits aldosterone synthesis by covalently targeting CYP11A1 to attenuate hypertension.

Introduction: Tetrandrine (Tet) is the main pharmacological component of Stephania tetrandra S. Moore, which is a well-documented traditional Chinese medicine known for its diuretic and antihypertensive properties. Unraveling the specific targets and mechanisms of Tet involved in inducing diuresis and mitigating hypertension can provide valuable insights into its therapeutic effects. This study aimed to explore the diuretic and antihypertensive targets and mechanisms of Tet using chemical biology coupled with activity analyses in vivo and in vitro. Methods: The diuretic effects of Tet were evaluated using a water-loaded mouse model. The direct target proteins for the diuretic and antihypertensive effects of Tet were determined using chemical biology. Furthermore, the molecular mechanism of Tet binding to target proteins was analyzed using a multidisciplinary approach based on the structure and function of the proteins. Finally, the effects of the Tet-targeted protein on downstream signaling pathways and blood pressure were evaluated in hypertensive model rats. Results: Tet exhibited significant antihypertensive and potassium-preserving diuretic effects. The mechanism underlying these effects involves the modulation of the enzyme activity by covalent binding of Tet to Cys423 of CYP11A1. This interaction alters the stability of heme within CYP11A1, subsequently impeding electron transfer and inhibiting aldosterone biosynthesis. Discussion: This study not only revealed the mechanism of the diuretic and antihypertensive effects of Tet but also discovered a novel covalent inhibitor of CYP11A1. These findings contribute significantly to our understanding of the therapeutic potential of Tet and provide a foundation for future research in the development of targeted treatments for hypertension.

Feasibility assessment of a clean and efficient fire extinguishing system for pottery jar liquor warehouses.

Clean fire extinguishing systems applicable to the pottery jar liquor warehouse are in demand. In this study, taking 53vol% liquor as the research subject, fire models of various clean fire extinguishing systems comprising water mist, liquid carbon dioxide (LCO2) and liquid nitrogen (LN2) were established using a fire dynamic simulator to determine their fire extinguishing effect. A feasibility assessment of systems was performed under different fire source types, fire source sizes, and ventilation conditions. The fire extinguishing efficiency was analyzed in terms of the fire extinguishing time, oxygen concentration, and space temperature. The results showed that the success rate of the LCO2 and LN2 fire extinguishing systems was 100%, whereas the success rate of the water mist fire extinguishing system was 95%. In terms of reducing the oxygen concentration at the bottom of the space and the temperature in the space, the LCO2 system exhibited the best performance, followed by the LN2 system, and lastly the water mist. Under different ventilation conditions and fire source types, the LCO2 fire extinguishing system was least affected, whereas the effectiveness of the water mist fire extinguishing system reduced under natural ventilation conditions, and the extinguishing efficiency of the LN2 fire extinguishing system was affected by the fire source type. Overall, the LCO2 system presented more advantages in extinguishing fires in pottery jar liquor warehouses and can provide a new idea for the development and application of clean and efficient fire extinguishing systems.

Phillyrin and its metabolites treat pulmonary embolism by targeting PLCß3 to inhibit platelet activation.

ETHNOPHARMACOLOGICAL RELEVANCE: Lian Qiao (LQ), the dried fruit of Forsythia suspensa (Thunb.) Vahl, is a well-documented traditional Chinese medicine known for its detoxifying and heat-clearing properties. Clinically, compounds containing LQ are widely used to treat thrombotic diseases, indicating that it may have antithrombotic effects. However, its exact mechanism of action remains unknown. AIM OF THE STUDY: This study aimed to verify the antithrombotic effect of LQ and further explore the material basis and target mechanism of its antithrombotic effect using various biological methods. MATERIALS AND METHODS: An epinephrine-collagen-thrombin-induced mouse model of acute pulmonary embolism (APE) was established to study the effects of LQ on thrombus development. A UPLC/Q/TOF-MS screening and identification system based on the inhibition of platelet aggregation and Ca2+ antagonism was established to determine the pharmacodynamic components of LQ that inhibit platelet activation. The inhibitory effect of active ingredients on platelet activation, and the determination of the target of their inhibitory effect on platelet activation have been studied using chemical proteomics. Furthermore, based on the structure and function of the target protein, a multidisciplinary approach was adopted to analyze the molecular mechanism of active ingredient binding to target proteins and to evaluate the effects of active ingredients on the downstream signaling pathways of target proteins. RESULTS: LQ showed significant anticoagulant effects in APE model mice. Phillyrin and phillygenin were the antiplatelet-activating components of LQ. PLCß3 was identified as a target for inhibiting platelet activation by phillyrin and its metabolites. The mechanism underlying the effect involves phillyrin and its metabolites inhibiting PLCß3 activity by blocking the binding of PLCß3 to Gαq through non-covalently targeting the ASN260 of PLCß3, thus inhibiting the downstream Gαq-PLCß3-Ca2+ signaling pathway, effectively hindering platelet activation and therefore playing an anticoagulant role. CONCLUSION: This study not only proposes and validates the antithrombotic effect of LQ for the first time but also finds that phillyrin and phillygenin are the main pharmacological substances through which LQ exerts antithrombotic activity and reveals a novel mechanism by which they exert antiplatelet activity by directly targeting and inhibiting PLCß3 activity. These findings significantly contribute to our understanding of the therapeutic potential of phillyrin and provide important clues for the discovery and development of new antiplatelet drugs.

Resveratrol targeting NRF2 disrupts the binding between KEAP1 and NRF2-DLG motif to ameliorate oxidative stress damage in mice pulmonary infection.

ETHNOPHARMACOLOGICAL RELEVANCE: The root of Polygonum cuspidatum Sieb. et Zucc (PC), known as 'Huzhang' in the Chinese Pharmacopoeia, has been traditionally employed for its anti-inflammatory, antiviral, antimicrobial, and other biological activities. Polydatin (PD) and its aglycone, resveratrol (RES), are key pharmacologically active components responsible for exerting anti-inflammatory and antioxidant effects. However, its specific targets and action mechanisms remain unclear. AIM OF THE STUDY: The equilibrium of the KEAP1-NRF2 system serves as the primary protective response to oxidative and electrophilic stresses within the body, particularly in cases of acute lung injury caused by pathogenic microbial infection. In this study, the precise mechanisms by which RES alleviates oxidative stress damage in conjunction with NRF2 activators are discussed. MATERIALS AND METHODS: The active components from PC were screened to evaluate their potential to inhibit reactive oxygen species (ROS) and activate antioxidant activity dependent on antioxidant response elements (ARE). RES was evaluated for its potential to alleviate the oxidative stress caused by pathogenic microbial infection. Functional probes were designed to study the RES distribution and identify its targets. A lipopolysaccharide (LPS)-induced oxidative injury model was used to evaluate the effects of RES on the KEAP1-NRF2/ARE pathway in RAW 264.7 cells. The interaction between RES and NRF2 was elucidated using drug-affinity responsive target stability (DARTS), cellular thermal shift assays (CETSA), co-immunoprecipitation (Co-IP), and microscale thermophoresis (MST) techniques. The key binding sites were predicted using molecular docking and validated in NRF2-knockdownand reconstructed cells. Finally, protective effects against pulmonary stress were verified in a mouse model of pathogenic infection. RESULTS: The accumulation of RES in lung macrophages disrupted the binding between KEAP1 and NRF2, thereby preventing the ubiquitination degradation of NRF2 through its interaction with Ile28 on the NRF2-DLG motif. The activation of NRF2 resulted in the upregulation of nuclear transcription, enhances the expression of antioxidant genes dependent on ARE, suppresses ROS generation, and ameliorates oxidative damage both in vivo and in vitro. CONCLUSION: These findings shed light on the potential of RES to mitigate oxidative stress damage caused by pathogenic microorganism-induced lung infections and facilitate the discovery of novel small molecule modulators targeting the KEAP1-NRF2 DLG motif interaction.

Controllable Phase Separation Engineering of Iron-Cobalt Alloy Heterojunction for Efficient Water Oxidation.

The tailor-made transition metal alloy-based heterojunctions hold a promising prospect for the electrocatalytic oxygen evolution reaction (OER). Herein, a series of iron-cobalt bimetallic alloy heterojunctions are purposely designed and constructed via a newly developed controllable phase separation engineering strategy. The results show that the phase separation process and alloy component distribution rely on the metal molar ratio (Fe/Co), indicative of the metal content dependent behavior. Theoretical calculations demonstrate that the electronic structure and charge distribution of iron-cobalt bimetallic alloy can be modulated and optimized, thus leading to the formation of an electron-rich interface layer, which likely tunes the d-band center and reduces the adsorption energy barrier toward electrocatalytic intermediates. As a result, the Fe0.25Co0.75/Co heterojunction exhibits superior OER activity with a low overpotential of 185 mV at 10 mA cm-2. Moreover, it can reach industrial-level current densities and excellent durability in high-temperature and high-concentration electrolyte (30 wt % KOH), exhibiting enormous potential for industrial applications.

Codonopsis radix: a review of resource utilisation, postharvest processing, quality assessment, and its polysaccharide composition.

Codonopsis radix is the dried root of C. pilosula (Franch.) Nannf., C. pilosula Nannf. var. modesta (Nannf.) L. T. Shen, or C. tangshen Oliv., constitutes a botanical medicine with a profound historical lineage. It encompasses an array of bioactive constituents, including polyacetylenes, phenylpropanoids, alkaloids, triterpenoids, and polysaccharides, conferring upon it substantial medicinal and edible values. Consequently, it has garnered widespread attention from numerous scholars. In recent years, driven by advancements in modern traditional Chinese medicine, considerable strides have been taken in exploring resources utilization, traditional processing, quality evaluation and polysaccharide research of Codonopsis radix. However, there is a lack of systematic and comprehensive reporting on these research results. This paper provides a summary of recent advances in Codonopsis research, identifies existing issues in Codonopsis studies, and offers insights into future research directions. The aim is to provide insights and literature support for forthcoming investigations into Codonopsis.

Predictive modeling for postoperative delirium in elderly patients with abdominal malignancies using synthetic minority oversampling technique.

BACKGROUND: Postoperative delirium, particularly prevalent in elderly patients after abdominal cancer surgery, presents significant challenges in clinical management. AIM: To develop a synthetic minority oversampling technique (SMOTE)-based model for predicting postoperative delirium in elderly abdominal cancer patients. METHODS: In this retrospective cohort study, we analyzed data from 611 elderly patients who underwent abdominal malignant tumor surgery at our hospital between September 2020 and October 2022. The incidence of postoperative delirium was recorded for 7 d post-surgery. Patients were divided into delirium and non-delirium groups based on the occurrence of postoperative delirium or not. A multivariate logistic regression model was used to identify risk factors and develop a predictive model for postoperative delirium. The SMOTE technique was applied to enhance the model by oversampling the delirium cases. The model's predictive accuracy was then validated. RESULTS: In our study involving 611 elderly patients with abdominal malignant tumors, multivariate logistic regression analysis identified significant risk factors for postoperative delirium. These included the Charlson comorbidity index, American Society of Anesthesiologists classification, history of cerebrovascular disease, surgical duration, perioperative blood transfusion, and postoperative pain score. The incidence rate of postoperative delirium in our study was 22.91%. The original predictive model (P1) exhibited an area under the receiver operating characteristic curve of 0.862. In comparison, the SMOTE-based logistic early warning model (P2), which utilized the SMOTE oversampling algorithm, showed a slightly lower but comparable area under the curve of 0.856, suggesting no significant difference in performance between the two predictive approaches. CONCLUSION: This study confirms that the SMOTE-enhanced predictive model for postoperative delirium in elderly abdominal tumor patients shows performance equivalent to that of traditional methods, effectively addressing data imbalance.

Experimental study on flow characteristics of jet ventilation in crossflow in confined mine spaces.

The increasing depth of mine excavation presents greater challenges in mine ventilation and in managing cooling energy consumption. Therefore, there is an urgent need for comprehensive research on jet ventilation influenced by low-speed crossflows. This study investigated the impact of flow velocity ratios (R) and jet exit diameters (d) on flow-field distribution and flow characteristics through velocity measurements and smoke flow visualization experiments. The results of the study revealed two distinct types of air lakes formed by jet ventilation in crossflow (JVIC), with one being wall-attached and the other suspended. Notably, a significant secondary flow phenomenon was observed in the near-field near the upper wall. Additionally, the deflection angle (θj) of JVIC decreases as R and d/D increase, leading to the formation and movement of a semi-confined point (SP) and a confined point (CP) in the -x direction. Moreover, the wall confinement effect diminishes the jet's diffusion and deflection ability in the -z direction, leading to increased penetration in the x direction. Before the formation of the SP, the deflection section of the jet lengthens, followed by a rapid shortening upon its formation. Finally, the study further developed empirical equations for the jet axial trajectory and diffusion width.

Influence of mudstone on coal spontaneous combustion characteristics and oxidation kinetics analysis.

To explore the spontaneous combustion characteristics and hazards of the low-temperature oxidation (LTO) stage in the process of spontaneous combustion of coal and mudstone, the pore structure, spontaneous combustion characteristic parameters, and exothermic characteristics of coal and mudstone were tested and studied, and the oxidation kinetic parameters were calculated. The results show that mudstone has a larger specific surface area and pore volume than coal. From the fractal characteristics, the pore structure of mudstone is more complex than that of coal. According to the comparison of theoretical and actual gas generation and oxygen consumption rate curves, it is found that there is an interaction between coal and mudstone in the LTO process. With the increase of mudstone mass ratio, gas production, and its oxygen consumption rate increase. Among them, CM-4 (Coal:Mudstone = 1:1) has the highest exothermic intensity and the exothermic factor (A) and fire coefficient (K) increase with the increase of mudstone content. The apparent activation energy of the mudstone sample is lower than that of the raw coal, indicating that the sample after adding mudstone is more likely to have spontaneous combustion in the LTO stage.

Ligustilide covalently binds to Cys703 in the pre-S1 helix of TRPA1, blocking the opening of channel and relieving pain in rats with acute soft tissue injury.

ETHNOPHARMACOLOGICAL RELEVANCE: The natural anodyne Ligustilide (Lig), derived from Angelica sinensis (Oliv.) Diels and Ligusticum chuanxiong Hort., has been traditionally employed for its analgesic properties in the treatment of dysmenorrhea and migraine, and rheumatoid arthritis pain. Despite the existing reports on the correlation between TRP channels and the analgesic effects of Lig, a comprehensive understanding of their underlying mechanisms of action remains elusive. AIM OF THE STUDY: The objective of this study is to elucidate the mechanism of action of Lig on the analgesic target TRPA1 channel. METHODS: The therapeutic effect of Lig was evaluated in a rat acute soft tissue injury model. The analgesic target was identified through competitive inhibition of TRP channel agonists at the animal level, followed by Fluo-4/Ca2+ imaging on live cells overexpressing TRP proteins. The potential target was verified through in-gel imaging, colocalization using a Lig-derived molecular probe, and a drug affinity response target stability assay. The binding site of Lig was identified through protein spectrometry and further analyzed using molecular docking, site-specific mutation, and multidisciplinary approaches. RESULTS: The administration of Lig effectively ameliorated pain and attenuated oxidative stress and inflammatory responses in rats with soft tissue injuries. Moreover, the analgesic effects of Lig were specifically attributed to TRPA1. Mechanistic studies have revealed that Lig directly activates TRPA1 by interacting with the linker domain in the pre-S1 region of TRPA1. Through metabolic transformation, 6,7-epoxyligustilide (EM-Lig) forms a covalent bond with Cys703 of TRPA1 at high concentrations and prolonged exposure time. This irreversible binding prevents endogenous electrophilic products from entering the cysteine active center of ligand-binding pocket of TRPA1, thereby inhibiting Ca2+ influx through the channel opening and ultimately relieving pain. CONCLUSIONS: Lig selectively modulates the TRPA1 channel in a bimodal manner via non-electrophilic/electrophilic metabolic conversion. The epoxidized metabolic intermediate EM-Lig exerts analgesic effects by irreversibly inhibiting the activation of TRPA1 on sensory neurons. These findings not only highlight the analgesic mechanism of Lig but also offer a novel nucleophilic attack site for the development of TRPA1 antagonists in the pre-S1 region.

Experimental Study on the Inhibition Effect of the Inhibitor on Coal Spontaneous Combustion Under Critical Temperature.

At present, related research on inhibitors has been gradually improved, but there is still a lack of research on the inhibition characteristics at specific release temperatures and the mechanism of inhibiting coal spontaneous combustion. Based on this, In this study, the inhibition characteristics of adding inhibitor to coal under critical temperature (R70) are studied in depth. In the experiment, lignite was selected as the research object, and four different types of inhibitors, MgCl2, triphenyl phosphite (TPPI), Phytic acid (PA), and melatonin, were applied to coal samples at room temperature and 70 °C, respectively. The temperature-programmed-gas chromatography test and Fourier infrared spectroscopy experiment were carried out, and the oxidation kinetic parameters were calculated to study the oxidation characteristics and micromechanism of the coal samples in the process of spontaneous combustion. The experimental results show that the amount of CO gas release and oxygen consumption rate are lower, and the inhibition rate and apparent activation energy are higher when the inhibitor is added under R70 than at room temperature. Under R70, the content of oxygen-containing functional group -COOH with higher activity of inhibitor is reduced, the generation of active sites is inhibited, the concentration of active center is reduced, the path of mutual transformation between active sites and oxygen-containing functional groups is blocked, and the active groups are promoted to form a relatively stable inert oxygen-containing ether bond, which reduces the spontaneous combustion tendency of coal.