Development and Validation of an Individualized Nomogram for Predicting Patent Foramen Ovale-Associated Stroke: Patent Foramen Ovale Morphology-Based Analysis.

BACKGROUND: We previously reported four patent foramen ovale (PFO) morphological types that influenced right-to-left shunt (RLS) grades. Herein, we aimed to study the relationship between PFO morphology and cryptogenic stroke (CS). We further developed a nomogram based on four PFO morphological types and functional parameters to guide clinicians in judging the risk of PFO-associated stroke. METHODS: This was a retrospective observational study involving adult patients with PFO between January 2020 and November 2022. Patients were divided into a PFO-associated stroke group (CS group) and a group without cryptogenic stroke (non-CS group). Four types of PFO and RLS grades were analyzed. Nomograms were made to predict PFO-associated stroke using multivariable logistic regression analysis. The discrimination performance of the model was internally validated and assessed using the receiver operating characteristic. RESULTS: We enrolled 389 patients (male, 182 patients; female, 207 patients) with PFO, the mean age was 43.3 ± 8.1 years. The derivation cohort comprised 293 patients (CS group, 186 patients; non-CS group, 107 patients). The predictive nomogram comprised PFO morphological types, interatrial septum (IAS) mobility distance, septum primum thickness, PFO channel length at rest, and contrast-transthoracic echocardiography (c-TTE) RLS grade during the Valsalva maneuver. A validation cohort was established (CS group, 61 patients; non-CS group, 35 patients). The model area under the curve (AUC) was 0.891 (95% confidence interval = 0.855-0.928) in the derivation cohort and 0.935 (95% confidence interval = 0.885-0.986) in the validation cohort. Calibration curve analysis showed that the nomogram had a C-index of 0.891 in the derivation cohort and 0.935 in the validation cohort. The decision curve analysis (DCA) indicated that the nomogram had clinical applicability. CONCLUSIONS: Adding four PFO morphological types improved the risk stratification capability for PFO-associated stroke. The nomogram can identify high or low-risk PFO individuals and select patients who will likely benefit from interventional device closure.

Advance care planning readiness among community-dwelling older adults and the influencing factors: a scoping review.

BACKGROUND: Advance care planning (ACP) is pivotal in mitigating end-of-life suffering and ensuring healthcare congruence with the values of older adults and dignity in death. Despite its paramount importance, the current readiness for ACP among community-dwelling older adults and the intricate influencing factors have yet to be explored. OBJECTIVE: To review the literature focusing on ACP readiness among community-dwelling older adults and the influencing factors. METHODS: A scoping review conducted using the Arksey and O'Malley (2005) framework. Electronic databases (PubMed, CINAHL, Cochrane, Web of Science, PsycINFO), as well as grey literature databases (OpenGrey and GreyLit.org) were searched to identify studies published in English between January 2012 and March 2023. RESULTS: 19 studies were selected, comprising 3 qualitative, 13 quantitative, 2 mixed-methods, and 1 review article. The study evaluated the readiness of older adults for ACP by examining their knowledge and attitudes. It categorizes influencing factors into intrinsic and extrinsic levels. This review revealed that the knowledge about ACP among older adults across all settings was limited. However, they had positive attitudes toward it. In addition, intrinsic factors including sociodemographic characteristics, psychological factors, and family relationships, along with extrinsic factors including health care professionals' attitudes and experience, as well as policies and laws, influenced the ACP readiness among older adults. CONCLUSIONS: This study established the groundwork for future ACP intervention trials, providing a theoretical framework to guide their design and implementation. operationalization.

A Multicenter Cohort Study on DNA Methylation for Endometrial Cancer Detection in Cervical Scrapings.

BACKGROUND: The increasing incidence of endometrial cancer (EC) has highlighted the need for improved early detection methods. This study aimed to develop and validate a novel DNA methylation classifier, EMPap, for EC detection using cervical scrapings. METHODS: EMPap incorporated the methylation status of BHLHE22 and CDO1, along with age and body mass index (BMI), into a logistic regression model to calculate the endometrial cancer methylation (EM) score for identifying EC in cervical scrapings. We enrolled 1297 patients with highly suspected EC, including 196 confirmed EC cases, and assessed the EMPap performance in detecting EC. RESULTS: EMPap demonstrated robust diagnostic accuracy, with an area under the curve of 0.93, sensitivity of 90.3%, and specificity of 89.3%. It effectively detected EC across various disease stages, grades, and histological subtypes, and consistently performed well across patient demographics and symptoms. EMPap correctly identified 87.5% of the type II ECs and 53.8% of premalignant lesions. Notably, compared with transvaginal ultrasonography (TVS) in patients with postmenopausal bleeding, EMPap exhibited superior sensitivity (100% vs. 82.0%) and specificity (85.2% vs. 38.5%). In asymptomatic postmenopausal women, EMPap maintained high sensitivity (89.5%) and negative predictive value (NPV) (98.3%). CONCLUSIONS: This study demonstrated the potential of EMPap as an effective tool for EC detection. Despite the limited sample size, EMPap showed promise for identifying type II EC and detecting over 50% of premalignant lesions. As a DNA methylation classifier, EMPap can reduce unnecessary uterine interventions and improve diagnosis and outcomes.

Overview of Methylation and Demethylation Mechanisms and Influencing Factors of Mercury in Water.

Mercury, particularly in its methylated form, poses a significant environmental and health risk in aquatic ecosystems. While the toxicity and bioaccumulation of mercury are well documented, there remains a critical gap in our understanding of the mechanisms governing mercury methylation and demethylation in aquatic environments. This review systematically examines the complex interplay of chemical, biological, and physical factors that influence mercury speciation and transformation in natural water systems. We provide a comprehensive analysis of methylation and demethylation processes, specifically focusing on the dominant role of methanogenic bacteria. Our study highlights the crucial function of hgcAB genes in facilitating mercury methylation by anaerobic microorganisms, an area that represents a frontier in current research. By synthesizing the existing knowledge and identifying key research priorities, this review offers novel insights into the intricate dynamics of mercury cycling in aquatic ecosystems. Our findings provide a theoretical framework to inform future studies and guide pollution management strategies for mercury and its compounds in aquatic environments.

Bortezomib induces cell apoptosis and increases the efficacy of αPD-1 in BCR::ABL T315I mutation CML by targeting UBE2Q1.

The BCR:ABL T315I mutation presents a significant challenge in the current management of Chronic Myeloid Leukemia (CML), highlighting the need to identify novel targets and drugs. In our study, we observed the elevated expression of UBE2Q1 in KBM5-T315I cells compared to KBM5 cells, where it interacted with DDX3, regulating its ubiquitination. Furthermore, we found that Bortezomib (BTZ) targeted UBE2Q1, reducing its protein level expression. Consequently, BTZ dose-dependently inhibited the growth vitality of KBM5-T315I cells, inducing increased ROS production, mitochondrial membrane potential collapse, cytochrome C release, and expression of apoptosis-related proteins. These events collectively induced apoptosis in KBM5-T315I cells. Moreover, BTZ enhanced the therapeutic effects of anti-PD-1 treatment. In NOD/SCID mice bearing KBM5-T315I cell line xenografts, BTZ administration (2 mg/kg, ip, every other day for 4 weeks) significantly inhibited the growth of KBM5-T315Iderived xenografts and extended survival. In conclusion, our study sheds new light on the BTZ-induced apoptosis mechanism, suggesting the potential of BTZ as a promising chemo-immunotherapy agent against BCR:ABL T315I mutation CML.

Effect of transcutaneous electrical acupoint stimulation at different frequencies on, mild hypertension: A randomized controlled trial.

BACKGROUND: Transcutaneous electrical acupoint stimulation (TEAS) may contribute to blood pressure (BP) control, but the evidence remains insufficient. Our objectives were to evaluate the impact of TEAS on hypertension and determine the optimal frequency. METHODS: A total of 120 hypertensive patients were randomly allocated to the TEAS-2Hz group, TEAS-10Hz group, or usual care control group in a 1:1:1 ratio. All patients were advised to continue their usual antihypertensive regimen. Additionally, patients in the TEAS groups received TEAS therapy 3 times per week for 4 weeks, with a 4-week follow-up. RESULTS: The primary outcome was the change in systolic BP (SBP) from baseline to week 4. Secondary outcomes included changes in diastolic BP (DBP), mean arterial pressure (MAP), heart rate (HR), heart rate variability (HRV), and 12-item health survey (SF-12) at different time points. Both TEAS groups showed reductions in SBP relative to control (TEAS-2Hz group vs. control, -4.70mmHg [95% CI, -7.00 to -2.40mmHg]; P < 0.001; TEAS-10Hz group vs. control, -8.66mmHg [95% CI, -10.97 to -6.36mmHg]; P < 0.001). TEAS-10Hz provided a significant decrease in SBP than TEAS-2Hz (-3.96mmHg [95% CI, -1.66 to -6.26mmHg]; P < 0.001). TEAS groups also exhibited reductions in DBP, MAP, HR, LF/HF ratio（LF/HF）, very low frequency (VLF), and normalized low frequency (LF norm), and an increase in normalized high frequency (HF norm) than control. No differences were observed among groups in low frequency (LF), high frequency (HF), total power (TP), very low frequency (VLF), and SF-12. CONCLUSION: TEAS might be a promising adjunctive therapy for hypertension, and the recommended frequency is 10Hz, which should be confirmed in larger trials.

Distinct effects of dilute acid prehydrolysate inhibitors on enzymatic hydrolysis and yeast fermentation.

The effects of dilute acid prehydrolysate from poplar were investigated and compared in the enzymatic hydrolysis, fermentation, and simultaneous saccharification fermentation (SSF) in this study. The improvement of enzymatic hydrolysis and fermentation with resin adsorption and surfactant addition has also been represented. A total of 16 phenolic alcohols, aldehydes, acids and 3 furan derivatives in the prehydrolysates were identified and quantified by gas chromatography/mass spectrometry (GC/MS). The degree of inhibition from the phenolic compounds (26.55%) in prehydrolysate on the enzymatic hydrolysis was much higher than carbohydrates-derived inhibitors (0.52-4.64%). Around 40% degree of inhibition was eliminated in Avicel enzymatic hydrolysis when 75% of prehydrolysates phenolic compounds were removed by resin adsorption. This showed distinguishing inhibition degrees of various prehydrolysate phenolic compounds. Inhibition of prehydrolysate on enzymatic hydrolysis was more dosage-dependent, while their suppression on the fermentation showed a more complicated mode: fermentation could be terminated by the untreated prehydrolysate, while a small number of prehydrolysate inhibitors even improved the glucose consumption and ethanol production in the fermentation. Correlated with this distinct inhibition modes of prehydrolysate, the improvement of Tween 80 addition in SSF was around 7.10% for the final ethanol yield when the glucose accumulation was promoted by 76.6%.

Iron Deposition and Functional Connectivity Differences in Females With Migraine Without Aura: A Comparative Study of Headache Sides.

BACKGROUND: The pathophysiological mechanisms underlying migraine without aura (MwoA) in females remain incompletely elucidated. Currently, the association between headache laterality and iron deposition (ID), and functional connectivity (FC) in female MwoA patients has not been fully studied. METHODS: We prospectively recruited 63 female patients with MwoA and 31 matched healthy controls (HC) from the hospital. ID and FC among the four groups were analyzed using two-sample t-tests (with cluster-wise family-wise error [FWE] correction). Pearson correlation analysis was used to evaluate the relationships between clinical variables and both ID and FC values. Significance level: p < 0.05. RESULTS: Compared to HC, left-sided MwoA exhibited differences in ID in various brain regions, including the cerebellum, left orbital inferior frontal gyrus, left calcarine gyrus, right putamen, and left caudate nucleus, as well as exhibited enhanced FC between the left lobule III of the cerebellum and the right superior temporal gyrus. Compared to bilateral MwoA, left-sided MwoA showed significantly enhanced in FC values in the left calcarine gyrus, the right precentral gyrus, the right postcentral gyrus, and the right lingual gyrus. Additionally, significant differences were observed in the Pearson correlations between clinical variables and both ID and FC in the female MwoA subgroups. CONCLUSION: Our study provided preliminary evidence indicating significant differences in ID, FC, and correlations among subgroups of female MwoA. This provides neuroimaging references for further subclassifying MwoA patients. This offers valuable insights into potential pathophysiological mechanisms linked to the brain functional impairment in female MwoA.

Discovery of Enantiopure (S)-Methoprene Derivatives as Potent Biochemical Pesticide Candidates.

(S)-Methoprene has been widely applied as a powerful biochemical pesticide to control disease vectors and other pestiferous arthropods of economic importance. As a juvenile hormone analogue, many products based on (S)-methoprene are developed and commercialized in the USA, Europe, and elsewhere. However, the agricultural use of (S)-methoprene and its analogues remains underexplored. Here, based on an intermediate derivatization strategy and structural modification, a series of enantiopure (S)-methoprene derivatives were designed for their expected bioactivity against two crop-threatening pests. Six compounds showed more than 2-fold stronger inhibition of emergence against Plutella xylostella than (S)-methoprene, among which one that was designated as B2 showed even superior activity to the conventional chemical pesticide and biopesticide with IE50 of 0.02 mg/L. Nine compounds exhibited over 2-fold higher bioactivity against Aphis craccivora growth than (S)-methoprene. The physicochemical property evaluation and toxicological test showed that the potent (S)-methoprene derivatives were low toxic to the nontarget organism and the environment. Molecular docking studies further demonstrated that the high bioactivity of B2 may be partially attributed to its great affinity for binding to juvenile hormone receptors of P. xylostella. The current study suggests that B2 is a biochemical pesticide candidate with potency to be developed as a new agrochemical for lepidopteran control.

Modulation of Charge Transport Layer for Perovskite Light-Emitting Diodes.

Perovskite light-emitting diodes (Pero-LEDs) have garnered significant attention due to their exceptional emission characteristics, including narrow full width at half maximum, high color purity, and tunable emission colors. Recent efficiency and operational stability advancements have positioned Pero-LEDs as a promising next-generation display technology. Extensive research and review articles on the compositional engineering and defect passivation of perovskite layers have substantially contributed to the development of multi-color and high-efficiency Pero-LEDs. However, the crucial aspect of charge transport layer (CTL) modulation in Pero-LEDs remains relatively underexplored. CTL modulation not only impacts the charge carrier transport efficiency and injection balance but also plays a critical role in passivating the perovskite surface, blocking ion migration, enhancing perovskite crystallinity, and improving light extraction efficiency. Therefore, optimizing CTLs is pivotal for further enhancing Pero-LED performance. Herein, this review discusses the roles of CTLs in Pero-LEDs and categorizes both reported and potential CTL materials. Then, various CTL optimization strategies are presented, alongside an analysis of the selection criteria for CTLs in high-performance Pero-LEDs. Finally, a summary and outlook on the potential of CTL modulation to further advance Pero-LED performances are provided.

Parishin Alleviates Pulmonary Fibrosis by Reducing CD38 Levels in Naturally Aging Mice.

Parishin, a natural compound, has demonstrated significant potential in mitigating age-related phenotypes and improving outcomes in age-associated diseases. Given that aging is a major risk factor for numerous chronic conditions, including pulmonary fibrosis, we investigated parishin's effects on cellular senescence and lung health. In our study, we treated mouse lung epithelial cells with parishin and observed a reduction in cellular senescence markers alongside an upregulation of sirtuin 1 (SIRT1). Building on these in vitro findings, we administered parishin to naturally aged mice. The treatment resulted in decreased pulmonary fibrosis and reduced DNA damage in lung tissue. Notably, we found that parishin treatment led to a reduction in Cluster of differentiation 38 (CD38) levels, concomitant with an increase in SIRT1 expression. These findings indicate that parishin may enhance lung function in aged mice, suggesting its potential as a therapeutic agent for treating age-related pulmonary disorders.

Tuning Work Function of Fe2N@C Nanosheets by Co Doping for Enhanced Lithium Storage.

Transition metal nitrides (TMNs) with high theoretical capacity and excellent electrical conductivity have great potential as anode materials for lithium-ion batteries (LIBs), but suffer from poor rate performance due to the slow kinetics. Herein, taking the Fe2N for instance, Co doping is utilized to enhance the work function of Fe2N, which accelerates the charge transfer and strengthens the adsorption of Li+ ions. The Fe2N nanoparticles with various Co dopants are anchoring on the surface of honeycomb porous carbon foam (named Cox-Fe2N@C). Co-doping can enlarge the work function of pristine Fe2N and thereby optimize the charging/discharging kinetics. The work function can be increased from 5.23 eV (pristine Fe2N) to 5.67 eV for Co0.3-Fe2N@C and 5.56 eV for Co0.1-Fe2N@C. As expected, the Co0.1-Fe2N@C electrode exhibits the highest specific capacity (673 mA h g-1 at 100 mA g-1) and remarkable rate capability (375 mA h g-1 at 5 000 mA g-1), outperforming most reported TMNs electrodes. Therefore, this work provides a promising strategy to design and regulate anode materials for high-performance and even commercially available LIBs.

Commentary: A road map for future data-driven urban planning and environmental health research.

Recent advances in data science and urban environmental health research utilise large-scale databases (100s-1000s of cities) to explore the complex interplay of urban characteristics such as city form and size, climate, mobility, exposure, and environmental health impacts. Cities are still hotspots of air pollution and noise, suffer urban heat island effects and lack of green space, which leads to disease and mortality burdens preventable with better knowledge. Better understanding through harmonising and analysing data in large numbers of cities is essential to identifying the most effective means of disease prevention and understanding context dependencies important for policy.

Predictive value of ZFHX4 mutation for the efficacy of immune checkpoint inhibitors in non-small cell lung cancer and melanoma.

Studies have shown that the Zinc finger homeobox 4 (ZFHX4) might be a factor in the prognosis of malignancies. However, little is known about the association between the ZFHX4 mutation and the effectiveness of immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) and melanoma. Three public ICIs-treated NSCLC cohorts were divided into discovery cohort (n=75) and validation cohort (n=62), which were used to evaluate the relationship between ZFHX4 mutation and ICIs effectiveness in NSCLC. Seven ICIs-treated melanoma cohorts (n = 418) were used to analyze the relationship between ZFHX4 mutation and immunotherapy efficacy in melanoma. NSCLC and skin cutaneous melanoma (SKCM) cohorts from The Cancer Genome Atlas (TCGA) were used to investigate underlying mechanism. Patients with ZFHX4 mutant-type (ZFHX4-Mut) showed a superior objective response rate (ORR) (P < 0.01) and longer progression-free survival (PFS) (P < 0.05) than patients with ZFHX4 wild-type (ZFHX4-WT) in NSCLC cohorts. In the melanoma cohorts, patients carrying ZFHX4-Mut had a higher ORR (P = 0.042) and longer overall survival (OS) (P = 0.011). Besides, patients with NSCLC and melanoma harboring ZFHX4-Mut had a higher tumor mutation burden (TMB) (P<0.001) and tumor neoantigen burden (TNB) (P<0.001) than those harboring ZFHX4-WT. ZFHX4 mutation was associated with higher levels of plasma B cells, activated CD4+ memory T cells, and CD8+ T cells. Seven DNA damage repair pathways were significantly enriched in the ZFHX4-Mut group. ZFHX4 mutation could serve as a predicter for the efficacy of ICIs therapy in NSCLC and melanoma.

Protective Role of Sulforaphane against Physiological Toxicity of Triphenyltin in Common Carp (Cyprinus carpio haematopterus).

This experiment mainly explored the protective role of sulforaphane (SFN) against physiological toxicity of triphenyltin (TPT) in Cyprinus carpio haematopterus. In total, 320 Fish (56.90 ± 0.40 g) were randomly divided into four groups with four replicates each. The control group was fed the basal diet, the TPT group (TPT) was exposed to 10 ng L-1 TPT on the basis of the control group, the SFN + TPT group (TPT + SFN) was fed a diet supplemented with 10 mg kg-1 SFN on the TPT group, and the SFN group (SFN) was fed a diet supplemented with 10 mg kg-1 SFN. After 56 days of breeding trials, the results showed that TPT exposure resulted in a remarkable decrease (p < 0.05) in final weight, weight gain rate (WGR), specific growth rate (SGR), and condition factor (CF), but an increase (p < 0.05) in feed conversion ratio (FCR) and hepatosomatic index (HSI) of fish. TPT treatment decreased (p < 0.05) the amounts of hematocrit (Hct) and hemoglobin (Hb), plasma complement component 3 (C3) and C4 contents, alternative complement pathway (ACH50), acid phosphatase (ACP) and lysozyme (LZM) activities, liver glutathione (GSH) content, catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPX) activities, interleukin 10 (IL-10), and SOD mRNA expressions, but increased (p < 0.05) plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, liver malonaldehyde (MDA) content, tumor Cyclooxygenase 2 (COX2), and necrosis factor α (TNFα), IL-1ß, and MDA mRNA expressions. A histological analysis of the liver showed that a higher occurrence rates of the hepatocyte hypertrophy, nuclear disappearance and hepatocyte vacuolization was observed in the hepatocytes of fish exposed to TPT, and it was accompanied by the dilation of hepatic sinusoids. In addition, the toxicity induced by TPT was significantly improved in the groups that were treated with SFN, and SFN was able to improve growth performance and immunity, alleviate TPT-induced changes in inflammatory factors, ameliorate oxidative stress, and increase the activity of antioxidant enzymes (p < 0.05). The addition of SFN also alleviated liver damage caused by TPT and protected the structural integrity of the liver. Overall, these findings suggest that TPT inhibited the growth, immunity, and antioxidant capacity of Cyprinus carpio haematopteru. Dietary SFN could be beneficial for growth promotion, immunity, antioxidant capacity, and protection of liver structural integrity. Therefore, SFN is a prospective feed supplement for ameliorating the damage caused to fish by TPT contamination.

Predicting the Risk of Loneliness in Children and Adolescents: A Machine Learning Study.

BACKGROUND: Loneliness is increasingly emerging as a significant public health problem in children and adolescents. Predicting loneliness and finding its risk factors in children and adolescents is lacking and necessary, and would greatly help determine intervention actions. OBJECTIVE: This study aimed to find appropriate machine learning techniques to predict loneliness and its associated risk factors among schoolchildren. METHODS: The data were collected from an ongoing prospective puberty cohort that was established in Chongqing, Southwest China. This study used 822 subjects (46.84% boys, age range: 11-16) followed in 2019. Five models, (a) random forest, (b) extreme gradient boosting (XGBoost), (c) logistic regression, (d) neural network, and (e) support vector machine were applied to predict loneliness. A total of 39 indicators were collected and 28 predictors were finally included for prediction after data pre-processing, including demographic, parental relationship, mental health, pubertal development, behaviors, and environmental factors. Model performance was determined by accuracy and AUC. Additionally, random forest and XGBoost were applied to identify the important factors. The XGBoost algorithm with SHAP was also used to interpret the results of our ML model. RESULTS: All machine learning performed with favorable accuracy. Compared to random forest (AUC: 0.87 (95%CI: 0.80, 0.93)), logistic regression (AUC: 0.80 (95%CI: 0.70, 0.89)), neural network (AUC: 0.80 (95%CI: 0.71, 0.89)), and support vector machine (AUC: 0.79 (95%CI: 0.79, 0.89)), XGBoost algorithm had the highest AUC values 0.87 (95%CI: 0.80, 0.93) in the test set, although the difference was not significant between models. Peer communication, index of general affect, peer alienation, and internet addiction were the top four significant factors of loneliness in children and adolescents. CONCLUSIONS: The results of this study suggest that machine learning has considerable potential to predict loneliness in children. This may be valuable for the early identification and intervention of loneliness.

Integrated metabolomics and network pharmacology to explore the clinical efficacy and mechanism of Yinchenhao decoction combined with nucleoside analogues on chronic hepatitis B.

Yinchenhao decoction (YCHD) is widely used in the treatment of damp-heat syndrome of chronic hepatitis B (CHB), but it remains unclear about the active compounds in YCHD and its potential mechanism for treating CHB. The purpose of this work is to evaluate the clinical efficacy of YCHD combined with nucleoside analogues (NAs) for the treatment of CHB. Besides, based on the exact clinical efficacy, we combined serum metabolomics and network pharmacology to screen differential metabolites and related pathways regulated by YCHD to investigate the possible mechanism for treating CHB. It revealed that NAs plus YCHD could significantly improve alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, increase HBV-DNA negative rate (P<0.05), reduce the levels of inflammatory factors and LSM (both P<0.05), regulate lipids (P<0.05), and improve the symptoms of traditional Chinese medicine (TCM) (P<0.05) in CHB patients. YCHD was relatively safe. It showed 30 active compounds including chlorogenic acid, geniposide, emodin, quercetin, kaempferol, ß-sitosterol and aloe emodin, and 115 key targets which were related to the regulation of lipids and reduction of oxidative stress related to the effect of YCHD in CHB in the network pharmacology analysis. We found 9 core targets and 4 key metabolites according to metabolomics, which were partly consistent with the network pharmacology findings. It proved that network pharmacology combined with metabolomics can well explain the "multi-component-multi-target" mechanism of complex TCM.

Novel Insights into the Kallikrein-Kinin System in Fulminant Myocarditis: Physiological Basis and Potential Therapeutic Advances.

Fulminant myocarditis (FM) is characterized by rapid cardiac deterioration often instigated by an inflammatory cytokine storm. The kallikrein-kinin system (KKS) is a metabolic cascade known for releasing vasoactive kinins, such as bradykinin-related peptides, possessing diverse pharmacological activities that include inflammation, regulation of vascular permeability, endothelial barrier dysfunction, and blood pressure modulation. The type 1 and type 2 bradykinin receptors (B1R and B2R), integral components of the KKS system, mediate the primary biological effects of kinin peptides. This review aims to offer a comprehensive overview of the primary mechanisms of the KKS in FM, including an examination of the structural components, regulatory activation, and downstream signaling pathways of the KKS. Furthermore, it explores the involvement of the tissue kallikrein/B1R/inducible nitric oxide synthase (TK/B1R/iNOS) pathway in myocyte dysfunction, modulation of the immune response, and preservation of endothelial barrier integrity. The potential therapeutic advances targeting the inhibition of the KKS in managing FM will be discussed, providing valuable insights for the development of clinical treatment strategies.

Aberrant dynamic functional connectivity of thalamocortical circuitry in major depressive disorder. / é‡åº¦æŠ‘éƒéšœç¢æ‚£è€ ä¸˜è„‘çš®å±‚çŽ¯è·¯çš„åŠ¨æ€åŠŸèƒ½è¿žæŽ¥å¼‚å¸¸.

Thalamocortical circuitry has a substantial impact on emotion and cognition. Previous studies have demonstrated alterations in thalamocortical functional connectivity (FC), characterized by region-dependent hypo- or hyper-connectivity, among individuals with major depressive disorder (MDD). However, the dynamical reconfiguration of the thalamocortical system over time and potential abnormalities in dynamic thalamocortical connectivity associated with MDD remain unclear. Hence, we analyzed dynamic FC (dFC) between ten thalamic subregions and seven cortical subnetworks from resting-state functional magnetic resonance images of 48 patients with MDD and 57 healthy controls (HCs) to investigate time-varying changes in thalamocortical FC in patients with MDD. Moreover, dynamic laterality analysis was conducted to examine the changes in functional lateralization of the thalamocortical system over time. Correlations between the dynamic measures of thalamocortical FC and clinical assessment were also calculated. We identified four dynamic states of thalamocortical circuitry wherein patients with MDD exhibited decreased fractional time and reduced transitions within a negative connectivity state that showed strong correlations with primary cortical networks, compared with the HCs. In addition, MDD patients also exhibited increased fluctuations in functional laterality in the thalamocortical system across the scan duration. The thalamo-subnetwork analysis unveiled abnormal dFC variability involving higher-order cortical networks in the MDD cohort. Significant correlations were found between increased dFC variability with dorsal attention and default mode networks and the severity of symptoms. Our study comprehensively investigated the pattern of alteration of the thalamocortical dFC in MDD patients. The heterogeneous alterations of dFC between the thalamus and both primary and higher-order cortical networks may help characterize the deficits of sensory and cognitive processing in MDD.