The association of platelet to white blood cell ratio with diabetes: a nationwide survey in China.

Background: Inflammation is integral to diabetes pathogenesis. The novel hematological inflammatory biomarker, platelet to white blood cell ratio (PWR), is linked with various conditions such as chronic kidney disease and stroke. However, the association of this novel clinical indicator with diabetes still remains unclear, which is investigated in this study. Materials and Methods: A total of 10,973 Chinese participants were included and grouped according to the tertiles of PWR (T1, T2, and T3 groups). Diagnosis of prediabetes and diabetes adhered to American Diabetes Association criteria. Binary logistic regression was adopted to assess the relationship between PWR and both diabetes and prediabetes. The dose-response relationship of PWR and diabetes was examined using restricted cubic spline regression. Subgroup and interaction analyses were conducted to investigate potential covariate interactions. Results: Individuals with higher PWR had better lifestyles and lipid profiles (all P < 0.05). After adjusting for all the covariates, the T2 group had a 0.83-fold (95% CI: 0.73-0.93, P < 0.01) risk of diabetes and that for the T3 group was 0.68-fold (95% CI: 0.60-0.78. P < 0.001). Dose-response analysis identified non-linear PWR-diabetes associations in the general population and females (both P < 0.05), but absent in males. Participants with prediabetes in the T2 and T3 groups had lower risks of diabetes (OR = 0.80 for the T2 group, P < 0.001 and 0.68 for the T3 group, P < 0.001) in the full models. All the sensitivity analysis support consistent conclusions. Conclusions: An increase in PWR significantly correlates with reduced diabetes risks. A non-linear PWR-diabetes relationship exists in the general population and females, but not in males. The correlation between PWR and diabetes indicates that PWR holds potentials in early identification and prevention of diabetes.

The chain mediating effect of spiritual well-being and anticipatory grief between benefit finding and meaning in life of patients with advanced lung cancer: Empirical research quantitative.

AIM: This study aimed to explore the chain mediating effect of spiritual well-being and anticipatory grief between benefit finding and meaning in life of patients with advanced lung cancer. DESIGN: This was a cross-sectional study. METHODS: The research included 400 patients with advanced lung cancer who attended REDACTE from December 2022 to August 2023 as the research subjects. Data were collected using a questionnaire including socio-demographic and clinical characteristics, the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being scale (FACIT-Sp-12), the Benefit Finding Scale (BFS), the Preparatory Grief in Advanced Cancer Patients Scale (PGAC), and the Meaning of Life Questionnaire (MLQ). The structural equation model (SEM) was used to analyse the relationship between benefit finding, spiritual well-being, anticipatory grief and meaning in life. RESULTS: There was a significant correlation between benefit finding, spiritual well-being, anticipatory grief, and meaning in life. Benefit finding could have a direct positive impact on meaning in life of patients with advanced lung cancer, but it could also indirectly affect meaning in life of patients with advanced lung cancer through three pathways: the mediating effect of spiritual well-being, the mediating effect of anticipatory grief and the chain mediating effect of spiritual well-being and anticipatory grief. Nursing staff should develop an integrated program of interventions to enhance the meaning in life of patients with advanced lung cancer.

A hybrid water quality prediction model based on variational mode decomposition and bidirectional gated recursive unit.

Water quality predicted accuracy is beneficial to river ecological management and water pollution prevention. Owing to water quality data has the characteristics of nonlinearity and instability, it is difficult to predict the change of water quality. This paper proposes a hybrid water quality prediction model based on variational mode decomposition optimized by the sparrow search algorithm (SSA-VMD) and bidirectional gated recursive unit (BiGRU). First, the sparrow search algorithm selects fuzzy entropy (FE) as the fitness function to optimize the two parameters of VMD, which improves the adaptability of VMD. Second, SSA-VMD is used to decompose the original data into several components with different center frequencies. Finally, BiGRU is employed to predict each component separately, which significantly improves predicted accuracy. The proposed model is validated using data about dissolved oxygen (DO) and the potential of hydrogen (pH) from the Xiaojinshan Monitoring Station in Qiandao Lake, Hangzhou, China. The experimental results show that the proposed model has superior prediction accuracy and stability when compared with other models, such as EMD-based models and other CEEMDAN-based models. The prediction accuracy of DO can reach 97.8% and pH is 96.1%. Therefore, the proposed model can provide technical support for river water quality protection and pollution prevention.

Efficacy and safety of psychedelics for the treatment of mental disorders: A systematic review and meta-analysis.

We aim to systematically review and meta-analyze the effectiveness and safety of psychedelics [psilocybin, ayahuasca (active component DMT), LSD and MDMA] in treating symptoms of various mental disorders. Web of Science, Embase, EBSCO, and PubMed were searched up to February 2024 and 126 articles were finally included. Results showed that psilocybin has the largest number of articles on treating mood disorders (N = 28), followed by ayahuasca (N = 7) and LSD (N = 6). Overall, psychedelics have therapeutic effects on mental disorders such as depression and anxiety. Specifically, psilocybin (Hedges' g = -1.49, 95% CI [-1.67, -1.30]) showed the strongest therapeutic effect among four psychedelics, followed by ayahuasca (Hedges' g = -1.34, 95% CI [-1.86, -0.82]), MDMA (Hedges' g = -0.83, 95% CI [-1.33, -0.32]), and LSD (Hedges' g = -0.65, 95% CI [-1.03, -0.27]). A small amount of evidence also supports psychedelics improving tobacco addiction, eating disorders, sleep disorders, borderline personality disorder, obsessive-compulsive disorder, and body dysmorphic disorder. The most common adverse event with psychedelics was headache. Nearly a third of the articles reported that no participants reported lasting adverse effects. Our analyses suggest that psychedelics reduce negative mood, and have potential efficacy in other mental disorders, such as substance-use disorders and PTSD.

A hybrid prediction model of dissolved oxygen concentration based on secondary decomposition and bidirectional gate recurrent unit.

Dissolved oxygen is one of the important comprehensive indicators of river water quality, which reflects the degree of pollution in the water body. Monitoring and predicting dissolved oxygen are an important tool for water quality management, which helps to effectively maintain water ecological balance and prevent environmental problems. A single model cannot describe the dynamic characteristics of dissolved oxygen sequence, which affects the prediction accuracy. In order to obtain more accurate dissolved oxygen prediction results, decomposition techniques are commonly used to extract the main fluctuations and trends of water quality sequences. However, the high-frequency modes obtained from decomposition are still unstable. To solve this problem, this paper proposed a hybrid prediction model of dissolved oxygen concentration based on secondary decomposition and bidirectional gate recurrent unit. Firstly, dissolved oxygen sequence is preliminarily decomposed by complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN) and obtain several intrinsic mode functions (IMF). The fuzzy entropy (FE) is calculated to quantify the complexity of the IMF. Then, variational mode decomposition improved by northern goshawk optimization is used to decompose the IMF with higher entropy. The nonlinearity and instability of the sequence are further weakened. Finally, the bidirectional gate recurrent unit (BiGRU) neural network is used to predict each IMF component, and the final prediction result is obtained by reconstructing the prediction results of each component. In order to verify the effectiveness of the proposed model, this paper selects the dissolved oxygen data of Xin'anjiang Reservoir as the research object. The experimental results show that the RMSE, MAE, MAPE, and R2 of the proposed model are 0.1164, 0.0894, 1.0403%, and 0.9939, respectively, which is best among other comparative prediction models (BP, LSTM, GRU, BiGRU, EMD-BiGRU, CEEMDAN-BiGRU, VMD-BiGRU, and GNO-VMD-BiGRU). Therefore, this model effectively deals with high volatility and nonlinear dissolved oxygen data and provides reference for water environment management and ecological protection.

Reprogramming of arachidonic acid metabolism using α-terpineol to alleviate asthma: insights from metabolomics.

Asthma is a chronic inflammatory disorder in airways with typical pathologic features of airway inflammation and mucus hypersecretion. α-Terpineol is a monocyclic terpene found in many natural plants and foods. It has been reported to possess a wide range of pharmacological activities including anti-inflammatory and expectorant effects. However, the role of α-terpineol in asthma and its potential protective mechanism have not been well elucidated. This study is designed to investigate the pharmacological effect and mechanism of α-terpineol on asthmatic mice using the metabolomics platform. A murine model of asthma was established using ovalbumin (OVA) sensitization and then challenged for one week. The leukocyte count and inflammatory cytokines in the bronchoalveolar lavage fluid (BALF), lung histopathology, inflammatory  infiltrate and mucus secretion were evaluated. An ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)-based metabolomics study was performed on lung tissues and serum to explore endogenous small molecule metabolites affected by α-terpineol in asthmatic mice. After α-terpineol treatment, leukocyte count, inflammatory cytokines in the BALF, and peribronchial inflammation infiltration were significantly downregulated. Goblet cell hyperplasia and mucus secretion were attenuated, with the level of Muc5ac in BALF decreased. These results proved the protective effect of α-terpineol against airway inflammation, mucus hypersecretion and Th1/Th2 immune imbalance. To further investigate the underlying mechanisms of α-terpineol in asthma treatment, UPLC-MS/MS-based metabolomics analysis was performed. 26 and 15 identified significant differential metabolites were found in the lung tissues and serum of the control, model and α-terpineol groups, respectively. Based on the above differential metabolites, enrichment analysis showed that arachidonic acid (AA) metabolism was reprogrammed in both mouse lung tissues and serum. 5-Lipoxygenase (5-LOX) and cysteinyl leukotrienes (CysLTs) are the key enzyme and the end product of AA metabolism, respectively. In-depth studies have shown that pretreatment with α-terpineol can alleviate asthma by decreasing the AA level, downregulating the expression of 5-LOX and reducing the accumulation of CysLTs in mouse lung tissues. In summary, this study demonstrates that α-terpineol is a potential agent that can prevent asthma via regulating disordered AA metabolism.

Insight gained via ultra-performance liquid chromatography tandem mass spectrometry-based metabolomics: Protective effect of Artemisia argyi H.Lév. & Vaniot essential oil on lipopolysaccharide-induced liver injury mice.

Artemisia argyi H.Lév. & Vaniot essential oil (AAEO) has shown pharmacological effects such as anti-inflammation, antioxidant, and anti-tumor properties. However, the protective effect of AAEO on lipopolysaccharide (LPS)-induced liver injury and its potential protective mechanism are still unclear. In this study, we used ultra-performance liquid chromatography tandem mass spectrometry metabolomics techniques to investigate the changes in liver tissue metabolites in mice exposed to LPS with or without AAEO treatment for 14 days. The biochemical results showed that compared with the control group, AAEO significantly reduced the levels of liver functional enzymes, suggesting a significant improvement in liver injury. In addition, the 18 differential metabolites identified by metabolomics were mainly involved in the reprogramming of arachidonic acid metabolism, tryptophan metabolism, and purine metabolism. AAEO could significantly inhibit the expression of COX-2, IDO1, and NF-κB; enhance the body's anti-inflammatory ability; and alleviate liver injury. In summary, our study identified the protective mechanism of AAEO on LPS-induced liver injury at the level of small molecular metabolites, providing a potential liver protective agent for the treatment of LPS-induced liver injury.

MAPRE3 as an epigenetic target of EZH2 restricts ovarian cancer proliferation in vitro and in vivo.

Ovarian cancer (OC) is a lethal gynecologic cancer and the common cause of death within women worldwide. The polycomb group protein enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase highly expressed in various tumors, including OC. However, the mechanistic basis of EZH2 oncogenic activity in OC remain incompletely understood. Bioinformatics analysis showed that the expression of MAPRE3 was lower in OC tissues than in normal tissues, and was positively correlated with the overall survival. MAPRE3 overexpression decreased cell growth, inducing cell cycle arrest and apoptosis in OC cells, whereas MAPRE3 silencing promoted proliferation and accelerated cell cycle progression of OC cells. The in vivo study validated that overexpression of MAPRE3 impeded tumor formation and growth of OC xenografts in nude mice. In addition, knockdown of EZH2 in OC cells downregulated H3K27me3 expression and increased MAPRE3 expression. Inhibiting EZH2 in OC cells reduced the enrichment of H3K27me3 on the promoter of MAPRE3. Furthermore, MAPRE3 silencing significantly reversed changes in the expression of cell cycle and apoptosis-related markers and cell growth mediated by EZH2 knockdown in OC cells. MAPRE3 functions as a suppressor of OC and is epigenetic repressed by EZH2, suggesting a potential therapeutic strategy for OC by targeting EZH2/MAPRE3 axis.

Boron-based ternary MgTa2B6 cluster: a turning nanoclock with dynamic structural fluxionality.

Boron-based complex clusters are a fertile ground for the exploration of exotic chemical bonding and dynamic structural fluxionality. Here we report on the computational design of a ternary MgTa2B6 cluster via global structural searches and quantum chemical calculations. The cluster turns out to be a new member of the molecular rotor family, closely mimicking a turning clock at the subnanoscale. It is composed of a hexagonal B6 ring with a capping Ta atom at the top and bottom, whereas the Mg atom is linked to one Ta site as a radial Ta-Mg dimer. These components serve as the dial, axis, and hand of a nanoclock, respectively. Chemical bonding analyses reveal that the inverse sandwich Ta2B6 motif in the cluster features 6π/6σ double aromaticity, whose electron counting conforms to the (4n + 2) Hückel rule. The Ta-Mg dimer has a Lewis-type σ bond, and the Mg site has negligible bonding with B6 ring. The ternary cluster can be formulated as an [Mg]0[Ta2B6]0 complex. Molecular dynamics simulations suggest that the cluster is structurally fluxional analogous to a nanoclock, even at a low temperature of 100 K. The Ta-Mg hand turns almost freely around the Ta2 axis and along the B6 dial. The tiny intramolecular rotation barrier is less than 0.3 kcal mol-1, being dictated by the bonding nature of double 6π/6σ aromaticity. The present system offers a new type of molecular rotor in physical chemistry.

Deep brain stimulation of ventromedial prefrontal cortex reverses depressive-like behaviors via BDNF/TrkB signaling pathway in rats.

AIM: Deep brain stimulation (DBS) is currently under investigation as a potential therapeutic approach for managing major depressive disorder (MDD) and ventromedial prefrontal cortex (vmPFC) is recognized as a promising target region. Therefore, the present study aimed to investigate a preclinical paradigm of bilateral vmPFC DBS and examine the molecular mechanisms underlying its antidepressant-like effects using chronic unpredictable stress (CUS) model in rats. MAIN METHODS: Male rats were subjected to stereotaxic surgery and deep brain stimulation paradigm in non-stressed and CUS rats respectively, and the therapeutic effect of DBS were assessed by a series of behavioral tests including sucrose preference test, open field test, elevated plus maze test, and forced swim test. The potential involvement of the BDNF/TrkB signaling pathway and its downstream effects in this process were also investigated using western blot. KEY FINDINGS: We identified that a stimulation protocol consisting of 130 Hz, 200 µA, 90 µs pulses administered for 5 h per day over a period of 7 days effectively mitigated CUS-induced depressive-like and anxiety-like behaviors in rats. These therapeutic effects were associated with the enhancement of the BDNF/TrkB signaling pathway and its downstream ERK1/2 activity. SIGNIFICANCE: These findings provide valuable insights into the potential clinical utility of vmPFC DBS as an approach of improving the symptoms experienced by individuals with MDD. This evidence contributes to our understanding of the neurobiological basis of depression and offers promise for the development of more effective treatments.

VGGish-based detection of biological sound components and their spatio-temporal variations in a subtropical forest in eastern China.

Passive acoustic monitoring technology is widely used to monitor the diversity of vocal animals, but the question of how to quickly extract effective sound patterns remains a challenge due to the difficulty of distinguishing biological sounds within multiple sound sources in a soundscape. In this study, we address the potential application of the VGGish model, pre-trained on Google's AudioSet dataset, for the extraction of acoustic features, together with an unsupervised clustering method based on the Gaussian mixture model, to identify various sound sources from a soundscape of a subtropical forest in China. The results show that different biotic and abiotic components can be distinguished from various confounding sound sources. Birds and insects were the two primary biophony sound sources, and their sounds displayed distinct temporal patterns across both diurnal and monthly time frames and distinct spatial patterns in the landscape. Using the clustering and modeling method of the general sound feature set, we quickly depicted the soundscape in a subtropical forest ecosystem, which could be used to track dynamic changes in the acoustic environment and provide help for biodiversity and ecological environment monitoring.

Activation of Epac in the BLA disrupts reconsolidation and attenuates heroin-seeking behaviour.

The susceptibility to drug cravings evoked by stimuli poses a formidable hurdle in the treatment of addiction and the prevention of relapse. Pharmacological interventions targeting drug-associated memories hold promise for curbing relapse by impeding the process of memory reconsolidation, predominantly governed by cAMP signalling. Exchange Protein Activated by cAMP (Epac) serves as a distinctive mediator of cAMP signalling, which has been implicated in reinforcing the effects of cocaine and facilitating the acquisition. Nonetheless, the role of Epac in heroin-related memory and the subsequent seeking behaviour remains enigmatic. In this study, we explored the impact of Epac activation on the reconsolidation process of drug-related memories associated with heroin self-administration. Over the course of 10 consecutive days, rats underwent training, wherein they acquired the behaviour of nose poking to obtain heroin accompanied by a tone + light cue. This nose-poking behaviour was subsequently extinguished when heroin infusion and cue presentation were discontinued. Subsequently, we administered 8-pCPT-cAMP (8-CPT), an Epac-specific activator, into the basolateral amygdala at various time points, either in the presence or absence of a conditioned stimulus. Our findings demonstrate that administering 8-CPT immediately after memory retrieval effectively reduces cue- and heroin-induced reinstatement, with the observed effects persisting significantly for a minimum of 28 days. However, infusion of 8-CPT for a duration of 6 h following the memory retrieval trial, or without it altogether, had no discernible impact. Thus, these findings strongly suggest that Epac activation can disrupt the reconsolidation of heroin-associated memory, thereby diminishing the reinstatement of heroin-seeking behaviour.

Perioperative sleep disorders in gynaecological daycase surgery patients and analysis of risk factors: protocol for a cross-sectional study.

INTRODUCTION: Sleep disorders are clinical syndromes of disturbed sleep-wake rhythms and abnormal sleep quality. They have various causes, but their main manifestations are difficulty falling asleep, sleep disruption and daytime fatigue. These are common clinical symptoms in perioperative patients, especially in gynaecological patients. There is a lack of research on the factors influencing perioperative sleep disorders in gynaecological patients. The aim of this study is to assess the prevalence of sleep disorders in gynaecological surgery patients and to analyse the possible factors influencing them to provide new ideas for improving sleep disorders in this patient population. METHODS AND ANALYSIS: This cross-sectional, descriptive and observational survey is planned to include 480 gynaecological day surgery patients. All patients who meet the inclusion criteria are eligible to join the study. The study will record preoperative diagnosis, surgical procedure, duration of surgery, type of anaesthesia, anaesthetic drugs, sleep quality, anxiety and depression levels and pain indices 30 days before and 1, 2, 3 and 30 days after surgery. ETHICS AND DISSEMINATION: The study was approved by the Ethics Committee of Beijing Shijitan Hospital Affiliated with Capital Medical University (Approval Number: sjtkyll-lx-2022(109)) before the start of recruitment. The results of the study will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: ChiCTR2200064533.

Cineole inhibits the biosynthesis of leukotrienes and prostaglandins to alleviate allergic rhinitis: Insights from metabolomics.

Allergic rhinitis (AR) is a common allergic disease characterized by nasal congestion, rhinorrhoea, and sneezing. Cineole, a monoterpenoid compound widely present in various volatile oils, has a wide range of pharmacological activities and is of interest in allergic airway diseases for its anti-inflammatory and anti-mucus production abilities. However, the protective effects of cineole in mice with allergic rhinitis and its mechanisms have not been well investigated. In this study, the protective effect of cineole against ovalbumin-induced (OVA-induced) allergic rhinitis and its molecular mechanism is investigated by metabolomic analysis based on ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). OVA combined with aluminum hydroxide adjuvant is used to sensitize and establish the allergic rhinitis (AR) mouse model. The mice are randomly divided into groups of control, AR, cineole (30 mg/kg), and budesonide (38.83 µg/kg). The pharmacodynamic results show that cineole significantly reduces the levels of Th2-type cytokines and OVA-specific IgE (OVA-sIgE) in AR mice, improves nasal mucosal tissue damage and alleviates nasal symptoms compared to the untreated AR group. Metabolomic results show that arachidonic acid (AA) metabolism and tryptophan (Trp) metabolism are reprogrammed on the basis of 27 significantly altered metabolites. Further studies show that cineole inhibits the biosynthesis of pro-inflammatory lipid mediators leukotrienes (LTs) and prostaglandins (PGs) in mice by inhibiting the activity of 5-lipoxygenase (5-LOX) and cyclooxygenase-2 (COX-2) in the arachidonic acid metabolic (AA metabolic) pathway. It also inhibits the production of Th2 cytokines and inflammatory cell infiltration, thereby alleviating symptoms such as nasal congestion and nasal leakage. These results reveal the action and molecular mechanism of cineole in alleviating AR and provide a theoretical basis for the clinical application of cineole in treating AR.

Hepatoprotective effect of Artemisia Argyi essential oil on bisphenol A-induced hepatotoxicity via inhibition of ferroptosis in mice.

The environmental pollutant bisphenol A (BPA), used in the manufacture of plastic packaging materials for various diets, is widely distributed in the environment and causes severe hepatotoxicity by inducing oxidative stress. Artemisia argyi essential oil (AAEO), a volatile oil component isolated from Artemisia argyi H.Lév. & Vaniot, has pharmacological effects, especially for hepatoprotective actions. However, the potential effect of AAEO in BPA induced hepatotoxicity has not been characterized. First, we analyzed the chemical composition in AAEO by gas chromatography-mass spectrometry. Herein, we investigated the effect of AAEO on hepatic metabolic changes in mice exposed to BPA. Results showed that compared with the BPA group, AAEO could reduce the level of liver function enzymes in BPA mice serum, and ameliorate hepatic lesions and fibrosis. Additionally, 20 differential metabolites screened by metabolomics were mainly involved in the reprogramming of glutathione metabolism, purine metabolism, and polyunsaturated fatty acid synthesis. Moreover, AAEO could reduce hepatic ferroptosis induced by BPA, as demonstrated by reducing xanthine oxidase activity, up-regulating the activities of glutathione peroxidase 4 (GPX4), superoxide dismutase, and catalase and the expression of SLC7A11 to promote the glutathione synthetic, while inhibiting transferrin receptor 1 (TFR1) expression to reduce the accumulation of Fe2+ in cells. Therefore, our study identified AAEO as a hepatic protectant against BPA-induced hepatotoxicity by reversing the occurrence of ferroptosis.

Baicalein Suppresses NLRP3 and AIM2 Inflammasome-Mediated Pyroptosis in Macrophages Infected by Mycobacterium tuberculosis via Induced Autophagy.

Mycobacterium tuberculosis (Mtb) continues to pose a significant threat to global health because it causes granulomas and systemic inflammatory responses during active tuberculosis (TB). Mtb can induce macrophage pyroptosis, which results in the release of IL-1ß and causes tissue damage, thereby promoting its spread. In the absence of anti-TB drugs, host-directed therapy (HDT) has been demonstrated to be an effective strategy against TB. In this study, we used an in vitro Mtb-infected macrophage model to assess the effect of baicalein, derived from Scutellariae radix, on pyroptosis induced in Mtb-infected macrophages. Further, we investigated the molecular mechanisms underlying the actions of baicalein. The results of the study suggest that baicalein inhibits pyroptosis in Mtb-infected macrophages by downregulating the assembly of AIM2 and NLRP3 inflammasome and promoting autophagy. Further research has also shown that the mechanism by which baicalein promotes autophagy may involve the inhibition of the activation of the Akt/mTOR pathway and the inhibition of the AIM2 protein, which affects the levels of CHMP2A protein required to promote autophagy. Thus, our data show that baicalein can inhibit Mtb infection-induced macrophage pyroptosis and has the potential to be a new adjunctive HDT drug. IMPORTANCE Current strategies for treating drug-resistant tuberculosis have limited efficacy and undesirable side effects; hence, research on new treatments, including innovative medications, is required. Host-directed therapy (HDT) has emerged as a viable strategy for modulating host cell responses in order to enhance protective immunity against infections. Baicalein, extracted from Scutellariae radix, was shown to inhibit pyroptosis caused by Mycobacterium tuberculosis-infected macrophages and was associated with autophagy. Our findings reveal that baicalein can be used as an adjunctive treatment for tuberculosis or other inflammatory diseases by regulating immune function and enhancing the antibacterial ability of the host. It also provides a new idea for exploring the anti-inflammatory mechanism of baicalein.

Ursolic Acid Promotes Autophagy by Inhibiting Akt/mTOR and TNF-α/TNFR1 Signaling Pathways to Alleviate Pyroptosis and Necroptosis in Mycobacterium tuberculosis-Infected Macrophages.

As a lethal infectious disease, tuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb). Its complex pathophysiological process limits the effectiveness of many clinical treatments. By regulating host cell death, Mtb manipulates macrophages, the first line of defense against invading pathogens, to evade host immunity and promote the spread of bacteria and intracellular inflammatory substances to neighboring cells, resulting in widespread chronic inflammation and persistent lung damage. Autophagy, a metabolic pathway by which cells protect themselves, has been shown to fight intracellular microorganisms, such as Mtb, and they also play a crucial role in regulating cell survival and death. Therefore, host-directed therapy (HDT) based on antimicrobial and anti-inflammatory interventions is a pivotal adjunct to current TB treatment, enhancing anti-TB efficacy. In the present study, we showed that a secondary plant metabolite, ursolic acid (UA), inhibited Mtb-induced pyroptosis and necroptosis of macrophages. In addition, UA induced macrophage autophagy and enhanced intracellular killing of Mtb. To investigate the underlying molecular mechanisms, we explored the signaling pathways associated with autophagy as well as cell death. The results showed that UA could synergistically inhibit the Akt/mTOR and TNF-α/TNFR1 signaling pathways and promote autophagy, thus achieving its regulatory effects on pyroptosis and necroptosis of macrophages. Collectively, UA could be a potential adjuvant drug for host-targeted anti-TB therapy, as it could effectively inhibit pyroptosis and necroptosis of macrophages and counteract the excessive inflammatory response caused by Mtb-infected macrophages via modulating the host immune response, potentially improving clinical outcomes.

Psychometric properties of the Chinese version of the self-care scale for older adults undergoing hip fracture surgery: A translation and validation study.

Objective: The purpose of this study was to translate and verify the reliability and validity of the Chinese version of the self-care scale for older adults undergoing hip fracture surgery. Methods: A total of 502 older adult/adults patients after hip fracture surgery were recruited from Liaoning, Shanxi, and Beijing, China. The reliability of the Chinese version of the scale was measured by internal consistency, split-half reliability, and retest reliability, and the validity was evaluated by the content validity index and structure validity index. Results: The Chinese version of the HFS-SC scale had a Cronbach's alpha coefficient of 0.848, and the Cronbach's alpha coefficients for the five dimensions ranged from 0.719 to 0.780. The split-half reliability of the scale was 0.739, and the retest reliability was 0.759. The content validity index (S-CVI) was 0.932. The five-factor structure, supported by the eigenvalues, total variance explained, and the scree plot accounted for 66.666% of the total variance. In confirmatory factor analysis, the model fit results were as follows, X2/df = 1.847, GFI = 0.914, AGFI = 0.878, PGFI = 0.640, IFI = 0.932, TLI = 0.912, CFI = 0.931, RMSEA = 0.058, PNFI = 0.679. The indicators of the model's fit were within reasonable bounds. Conclusion: The Chinese version of the self-care scale for older adults undergoing hip fracture surgery has suitable reliability and validity. The scale can be used to assess the level of older adult/adults self-care in China following hip replacement surgery and serves as a useful benchmark for identifying potential intervention targets to raise the level of older adult/adults self-care following hip replacement surgery.

Coupling in-syringe kapok fiber-supported liquid-phase microextraction with flow injection-mass spectrometry for rapid and green biofluid analysis: Determination of antidepressants as an example.

Quantification of substances in biofluid samples (e.g., urine, blood, and cerebrospinal fluids) are useful for clinical diagnosis. In current study, a rapid and green strategy by coupling in-syringe kapok fiber-supported liquid-phase microextraction with flow-injection mass spectrometry was proposed. The natural kapok fiber was used as an oily extraction solvent (e.g., n-octanol) support material, and an in-syringe extraction device was conveniently constructed. The whole extraction processes, including sampling, washing and desorption, were conveniently conducted by simply pulling/pushing the syringe plunger, enabling rapid analyte enrichment and sample purification. The follow-up flow injection-mass spectrometry detection enabled rapid and high throughput analysis. As an example, the proposed method was applied to analyze antidepressants in plasma/urine, showing satisfied linearities (R2 ≥0.993) in ranges of 0.2-1000 ng/mL. By employing the in-syringe extraction method prior to flow injection-mass spectrometry detection, the LOQs in plasma and urine were reduced by 25-80 folds and 5-25 folds, respectively. Besides, by employing ethanol and 80% ethanol as the desorption solvent and carrier solvent, respectively, the analytical method showed excellent greenness. In general, the integrated method provides a promising choice for rapid and green biofluid analysis.