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.

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.

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.

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.

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.

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.

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.

Prediction Model of Lean Coal Adsorption of Power Plant Flue Gas.

To minimize errors in calculating coal flue gas adsorption capacity due to gas compressibility and to preclude prediction inaccuracies in abandoned mine flue gas storage capacity for power plants, it is imperative to account for the influence of compression factor calculation accuracy while selecting the optimal theoretical adsorption model. In this paper, the flue gas adsorption experiment of a power plant with coal samples gradually pressurized to close to 5 MPa at two different temperatures is carried out, and the temperature and pressure data obtained from the experiment are substituted into five different compression factor calculation methods to calculate different absolute adsorption amounts. The calculated adsorption capacities were fitted into six theoretical adsorption models to establish a predictive model suitable for estimating the coal adsorption capacity in power plant flue gas. Results reveal significant disparities in the absolute adsorption capacity determined by different compression factors, with an error range of 0.001278-7.8262 (cm3/kg). The Redlich-Kwong equation of state emerged as the most suitable for the flue gas of the selected experimental coal sample and the chosen composition ratio among the five compression factors. Among the six theoretical adsorption models, the Brunauer-Emmett-Teller model with three parameters demonstrated the highest suitability for predicting the adsorption capacity of coal samples in power plant smoke, achieving a fitting accuracy as high as 0.9922 at 49.7 °C.

Sinapine targeting PLCß3 EF hands disrupts Gαq-PLCß3 interaction and ameliorates cardiovascular diseases.

BACKGROUND: The renin-angiotensin-aldosterone system (RAAS) over-activation is highly involved in cardiovascular diseases (CVDs), with the Gαq-PLCß3 axis acting as a core node of RAAS. PLCß3 is a potential target of CVDs, and the lack of inhibitors has limited its drug development. PURPOSE: Sinapine (SP) is a potential leading compound for treating CVDs. Thus, we aimed to elucidate the regulation of SP towards the Gαq-PLCß3 axis and its molecular mechanism. STUDY DESIGN: Aldosteronism and hypertension animal models were employed to investigate SP's inhibitory effect on the abnormal activation of the RAAS through the Gαq-PLCß3 axis. We used chemical biology methods to identify potential targets and elucidate the underlying molecular mechanisms. METHODS: The effects of SP on aldosteronism and hypertension were evaluated using an established animal model in our laboratory. Target identification and underlying molecular mechanism research were performed using activity-based protein profiling with a bio-orthogonal click chemistry reaction and other biochemical methods. RESULTS: SP alleviated aldosteronism and hypertension in animal models by targeting PLCß3. The underlying mechanism for blocking the Gαq-PLCß3 interaction involves targeting the EF hands through the Asn-260 amino acid residue. SP regulated the Gαq-PLCß3 axis more precisely than the Gαq-GEFT or Gαq-PKCζ axis in the cardiovascular system. CONCLUSION: SP alleviated RAAS over-activation via Gαq-PLCß3 interaction blockade by targeting the PLCß3 EF hands domain, which provided a novel PLC inhibitor for treating CVDs. Unlike selective Gαq inhibitors, SP reduced the risk of side effects compared to Gαq inhibitors in treating CVDs.

Aptamer-bivalent-cholesterol-mediated proximity entropy-driven exosomal protein reporter for tumor diagnosis.

Exosomal proteins from the parental cells are considered to be promising biomarker sets for precise tumor diagnostics and monitoring. However, the accurate quantitative analysis of low-abundance exosomal proteins remains challenging due to the heterogeneity of clinical samples. Here, we standardized the exosomal concentration with a fluorogenic membrane probe and developed an aptamer-bivalent-cholesterol-mediated Proximity Entropy-driven Exosomal Protein Reporter (PEEPR). The proposed PEEPR enables the in-situ analysis of multiple exosomal proteins by integrating bivalent cholesterol anchor (exosomal lipid bilayer) and aptamer (exosomal proteins) with a proximity entropy-driven circuit. Based on this strategy, we successfully achieved detection limits of 3.9 pg/mL exosomal GPC-3 and 3.4 pg/mL exosomal PD-L1. Notably, the standardization of exosome concentrations is designed to avoid errors due to biological heterogeneity. The results showed that evaluating the levels of exosomal GPC-3 and PD-L1 in clinical samples via this strategy could accurately differentiate healthy individuals, hepatitis B patients, and hepatocellular carcinoma patients. In summary, PEEPR is a promising clinical diagnostic strategy for the quantitative analysis of a variety of tumor-associated exosomal proteins for the precise diagnosis and personalized treatment monitoring of tumors.

Catalpolaglycone disrupts mitochondrial thermogenesis by specifically binding to a conserved lysine residue of UCP2 on the proton leak tunnel.

BACKGROUND: Catalpol (CAT), a naturally occurring iridoid glycoside sourced from the root of Rehmannia glutinosa, affects mitochondrial metabolic functions. However, the mechanism of action of CAT against pyrexia and its plausible targets remain to be fully elucidated. PURPOSE: This study aimed to identify the specific targets of CAT for blocking mitochondrial thermogenesis and to unveil the unique biological mechanism of action of the orthogonal binding mode between the hemiacetal group and lysine residue on the target protein in vivo. METHODS: Lipopolysaccharide (LPS)/ carbonyl cyanide 3-chlorophenylhydrazone (CCCP)-induced fever models were established to evaluate the potential antipyretic effects of CAT. An alkenyl-modified CAT probe was designed to identify and capture potential targets. Binding capacity was tested using in-gel imaging and a cellular thermal shift assay. The underlying antipyretic mechanisms were explored using biochemical and molecular biological methods. Catalpolaglycone (CA) was coupled with protein profile identification and molecular docking analysis to evaluate and identify its binding mode to UCP2. RESULTS: After deglycation of CAT in vivo, the hemiacetal group in CA covalently binds to Lys239 of UCP2 in the mitochondria of the liver via an ɛ-amine nucleophilic addition. This irreversible binding affects proton leakage and improves mitochondrial membrane potential and ADP/ATP transformation efficiency, leading to an antipyretic effect. CONCLUSION: Our findings highlight the potential role of CA in modulating UCP2 activity or function within the mitochondria and open new avenues for investigating the therapeutic effects of CA on mitochondrial homeostasis.

Triboelectric Contact Localization Electronics: A Systematic Review.

The growing demand from the extended reality and wearable electronics market has led to an increased focus on the development of flexible human-machine interfaces (HMI). These interfaces require efficient user input acquisition modules that can realize touch operation, handwriting input, and motion sensing functions. In this paper, we present a systematic review of triboelectric-based contact localization electronics (TCLE) which play a crucial role in enabling the lightweight and long-endurance designs of flexible HMI. We begin by summarizing the mainstream working principles utilized in the design of TCLE, highlighting their respective strengths and weaknesses. Additionally, we discuss the implementation methods of TCLE in realizing advanced functions such as sliding motion detection, handwriting trajectory detection, and artificial intelligence-based user recognition. Furthermore, we review recent works on the applications of TCLE in HMI devices, which provide valuable insights for guiding the design of application scene-specified TCLE devices. Overall, this review aims to contribute to the advancement and understanding of TCLE, facilitating the development of next-generation HMI for various applications.

Honokiol targeting ankyrin repeat domain of TRPV4 ameliorates endothelial permeability in mice inflammatory bowel disease induced by DSS.

ETHNOPHARMACOLOGICAL RELEVANCE: As a classic traditional Chinese medicine, Magnolia officinalis (M. officinalis) is widely used in digestive diseases. It has rich gastrointestinal activity including inflammatory bowel disease (IBD) treatment, but the mechanism is not clear. AIM OF THE STUDY: In recent years, there has been a growing interest in investigating the regulatory effects of herbal compounds on transient receptor potential (TRP) channel proteins. Transient receptor potential vanilloid 4 (TRPV4), a subtype involved in endothelial permeability regulation, was discussed as the target of M. officinalis in the treatment of IBD in the study. Based on the targeting effect of TRPV4, this study investigated the active ingredients and mechanism of M. officinalis extract in treating IBD. MATERIALS AND METHODS: To reveal the connection between the active ingredients in M. officinalis and TRPV4, a bioactivity-guided high performance liquid chromatography system coupled with mass spectrometry identification was utilized to screen for TRPV4 antagonists. TRPV4 siRNA knockdown experiment was employed to validate the significance of TRPV4 as a crucial target in regulating endothelial permeability by honokiol (HON). The interaction of the active ingredient representing HON with TRPV4 was confirmed by molecular docking, fluorescence-based thermal shift and live cell calcium imaging experiments. The potential binding sites and inhibitory mechanisms of HON in TRPV4 were analyzed by molecular dynamics simulation and microscale thermophoresis. The therapeutic effect of HON based on TRPV4 was discussed in DSS-IBD mice. RESULTS: Our finding elucidated that the inhibitory activity of M. officinalis against TRPV4 is primarily attributed to HON analogues. The knockdown of TRPV4 expression significantly impaired the calcium regulation and permeability protection in endothelial cells. The mechanism study revealed that HON specifically targets the Q239 residue located in the ankyrin repeat domain of TRPV4, and competitively inhibits channel opening with adenosine triphosphate (ATP) binding. The immunofluorescence assay demonstrated that the administration of HON enhances the expression and location of VE-Cadherin to protect the endothelial barrier and attenuates immune cell infiltration. CONCLUSIONS: The finding suggested that HON alleviates IBD by improving endothelial permeability through TRPV4. The discovery provides valuable insights into the potential therapeutic strategy of active natural products for alleviating IBD.

Solid waste filling and roadway retaining for longwall mining by numerical investigation.

Solid waste filling and roadway retaining can effectively control surface subsidence and alleviate solid waste accumulation pollution. In order to effectively evaluate the advantages of solid waste filling in deformation control of overlying strata and surrounding rock of retained roadways, this study used theoretical analysis and numerical simulation methods to analyze the factors affecting surface subsidence, as well as the deformation characteristics of surrounding rocks and retaining tunnels during backfill mining. By calculating the influence of factors such as the foundation coefficient and the filling rate on the subsidence of the roof, it is concluded that the filling rate is the main controlling factor affecting the subsidence of the roof. Through simulation and comprehensive analysis of the impact of different filling rates on overlying rock migration, it was found that when the filling rates are 70 % and 80 %, it can effectively control the subsidence of overlying rock in the mining area. By simulating the effects of these two filling rate conditions on the deformation of surrounding rock within the retained roadway zone, the results show that the optimal filling rate that can effectively control the subsidence of the overlying rock and improve the stability of the retained roadway is 80 %.

KCNH2 mutation c.3099_3112del causes congenital long QT syndrome type 2 with gender differences.

INTRODUCTION: Long QT Syndrome (LQTS) is an inherited disease with an abnormal electrical conduction system in the heart that can cause sudden death as a result of QT prolongation. LQT2 is the second most common subtype of LQTS caused by loss of function mutations in the potassium voltage-gated channel subfamily H member 2 (KCNH2) gene. Although more than 900 mutations are associated with the LQTS, many of these mutations are not validated or characterized. METHODS AND RESULTS: Sequencing analyses of genomic DNA of a family with LQT2 identified a putative mutation. i.e., KCNH2(NM_000238.3): c.3099_3112del, in KCNH2 gene which appeared to be a definite pathogenic mutation. The family pedigree information showed a gender difference in clinical features and T-wave morphology between male and female patients. The female with mutation exhibited recurring ventricular arrhythmia and syncope, while two male carriers did not show any symptoms. In addition, T-wave in females was much flatter than in males. The female proband showed a positive reaction to the lidocaine test. Lidocaine injection almost completely blocked ventricular arrhythmia and shortened the QT interval by ≥30 ms. Treatment with propranolol, mexiletine, and implantation of cardioverter-defibrillators prevented the sustained ventricular tachycardia, ventricular fibrillation, and syncope, as assessed by a 3-year follow-up evaluation. CONCLUSIONS: A putative mutation c.3099_3112del in the KCNH2 gene causes LQT2 syndrome, and the pathogenic mutation mainly causes symptoms in female progeny.

Metabolic regularity of bioactive compounds in Bufei Jianpi granule in rats using ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry analysis technology.

Bufei Jianpi granule (BJG) is clinically effective for treating chronic obstructive pulmonary disease (COPD). At present, there is no report regarding the drug metabolism of BJG in vivo. This work developed an ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry method with high accuracy and sensitivity to determine drug metabolism of this compound in vivo. After continuous administration of BJG, the concentrations of 10 components in rat plasma, namely betaine, peimine, peiminine, astragaloside A, sinensetin, nobiletin, naringin, calycosin, formononetin, and magnolol, were determined at different time points. Meanwhile, the pharmacokinetic parameters and metabolic rules of these 10 components were evaluated: Cmax , 8.624-574.645 ng/mL; Tmax , 0.250-8.667 h; AUC0-t , 17.640-8947.393 ng h/mL; T1/2 , 3.405-66.014 h; mean residence time (MRT), 6.893-11.223 h. All these components possessed anti-inflammatory, antioxidant, and other biological activities to varying degrees, contributing to improving lung function, mitigating pneumonia and pulmonary fibrosis, and preventing and treating chronic obstructive pulmonary disease. Exploring the pharmacokinetic parameters and the laws of chemical components in BJG forms the scientific basis for applying the compound clinically and identifying quality markers for the control of the compound.

Study on thermal health and its safety management mode for the working environment.

Thermal health concerns have gained significant attention due to the heightened health risks faced by workers who are exposed to extreme thermal environments for prolonged periods. To ensure the occupational health and safety of such workers, and to enhance work efficiency, it is imperative to examine the characteristics of thermal health in the working environment. This study proposes three key elements of thermal health in the working environment, namely thermal health states, absence of heat-related illnesses, and heat adaptability, which can be used to develop a safety management framework for thermal health. By exploring the interconnections between these elements, the study summarizes their features and outlines the necessary precautions to safeguard them. The PDCA (plan/do/check/action) cycle management mode is utilized as a framework, with the three components of thermal health forming the core, to establish a safety management mode for thermal health. To ensure that employees work in a safe, healthy, comfortable, and productive environment, the assessment and control objectives of the thermal environment are regularly revised through the use of labor protection technology and thermal environment control technology. This paper presents a PDCA cycle safety management mode based on the characteristics of thermal health, which offers novel insights and approaches for assessing and managing workers' thermal health.

Efficacy and safety of ciprofol for long-term sedation in patients receiving mechanical ventilation in ICUs: a prospective, single-center, double-blind, randomized controlled protocol.

Introduction: Critically ill patients who receive mechanical ventilation after endotracheal intubation commonly experience discomfort and pressure. The major sedative drugs that are currently used in clinical practice present with many complications, such as hypotension, bradycardia, and respiratory depression. Ciprofol (HSK3486), which is a newly developed structural analog of propofol, is a short-acting gamma-aminobutyric acid (GABA) receptor agonist, and its mechanism of action is sedation or anesthesia by enhancing GABA-mediated chloride influx. The high efficacy of ciprofol for short-term sedation is comparable to that of propofol, and it has a relatively low incidence of adverse effects and high level of safety, which has been confirmed by multiple clinical studies. However, few studies have examined its safety and efficacy for long-term sedation. The purpose of the study is to evaluate the efficacy and safety of ciprofol for long-term sedation in mechanically ventilated patients. Methods: A prospective, single-center, double-blind, randomized, propofol-controlled, non-inferiority trial is proposed. The study will enroll 112 mechanically ventilated patients hospitalized in the intensive care unit (ICU) of the Shanghai Fourth People's Hospital affiliated with Tongji University based on the inclusion and exclusion criteria of the study, and randomly assign them to a group sedated with either ciprofol or propofol. The primary outcome is the percentage of time spent under target sedation, and secondary outcomes include drug dose, number of cases requiring additional dextrometropine, incidence of systolic blood pressure <80 or >180 mmHg, incidence of diastolic blood pressure <50 or >100 mmHg, incidence of heart rate <50 beats per minute (bpm) or >120 bpm, inflammatory indicators, blood lipid levels, liver and kidney functions, nutritional indicators, ventilator-free days within the 7-day period after enrollment, 28-day mortality, ICU stay duration, and hospitalization costs. Discussion: We hypothesize that the efficacy and safety of ciprofol for long-term sedation in mechanically ventilated ICU patients will not be inferior to that of propofol. Trial registration: Chinese Clinical Trials Registry identifier ChiCTR2200066951.

Guideline on treating community-acquired pneumonia with Chinese patent medicines.

Community-acquired pneumonia (CAP) is one of the most common infectious diseases, and its morbidity and mortality increase with age. Resistance and mutations development make the use of anti-infective therapy challenging. Chinese patent medicines (CPMs) are often used to treat CAP in China and well tolerable. However, currently there are no evidence-based guideline for the treatment of CAP with CPMs, and the misuse of CPMs is common. Therefore, we established a guideline panel to develop this guideline. We identified six clinical questions through two rounds of survey, and we then systematically searched relevant evidence and performed meta-analyses, evidence summaries and GRADE decision tables to draft recommendations, which were then voted on by a consensus panel using the Delphi method. Finally, we developed ten recommendations based on evidence synthesis and expert consensus. For the treatment of severe CAP in adults, we recommend Tanreqing injection, Reduning injection, Xuebijing injection, Shenfu injection, and Shenmai injection respectively. For the treatment of non-severe CAP in adults, we recommend Tanreqing injection, Reduning injection, Lianhua Qingwen capsule/granule, Qingfei Xiaoyan Pill and Shufeng Jiedu capsule respectively. CPMs have great potential to help in the fight against CAP worldwide, but more high-quality studies are still needed to strengthen the evidence.

Astragaloside IV protects against lung injury and pulmonary fibrosis in COPD by targeting GTP-GDP domain of RAS and downregulating the RAS/RAF/FoxO signaling pathway.

BACKGROUND: Pulmonary fibrosis is a chronic progressive interstitial lung disease characterized by the replacement of lung parenchyma with fibrous scar tissue, usually as the final stage of lung injury like COPD. Astragaloside IV (AST), a bioactive compound found in the Astragalus membranaceus (Fisch.) used in traditional Chinese medicine, has been shown to improve pulmonary function and exhibit anti-pulmonary fibrosis effects. However, the exact molecular mechanisms through which it combats pulmonary fibrosis, especially in COPD, remain unclear. PURPOSE: This study aimed to identify the potential therapeutic target and molecular mechanisms for AST in improving lung injury especially treating COPD type pulmonary fibrosis both in vivo and in vitro. METHODS: Multi lung injury models were established in mice using lipopolysaccharide (LPS), cigarette smoke (CS), or LPS plus CS to simulate the processes of pulmonary fibrosis in COPD. The effect of AST on lung function protection was evaluated, and proteomic and metabolomic analysis were applied to identify the signaling pathway affected by AST and to find potential targets of AST. The interaction between AST and wild-type and mutant RAS proteins was studied. The RAS/RAF/FoxO signaling pathway was stimulated in BEAS-2B cells and in mice lung tissues by LPS plus CS to investigate the anti-pulmonary fibrosis mechanism of AST analyzed by western blotting. The regulatory effects of AST on the RAS/RAF/FoxO pathway dependent on RAS were further confirmed using RAS siRNA. RESULTS: RAS was predicted and identified as the target protein of AST in anti-pulmonary fibrosis in COPD and improving lung function. The administration of AST was observed to impede the conversion of fibroblasts into myofibroblasts, reduce the manifestation of inflammatory factors and extracellular matrix, and hinder the activation of epithelial mesenchymal transition (EMT). Furthermore, AST significantly suppressed the RAS/RAF/FoxO signaling pathway in both in vitro and in vivo settings. CONCLUSION: AST exhibited lung function protection and anti-pulmonary fibrosis effect by inhibiting the GTP-GDP domain of RAS, which downregulated the RAS/RAF/FoxO signaling pathway. This study revealed AST as a natural candidate molecule for the protection of pulmonary fibrosis in COPD.