The Relationship Between Small Dense Low-Density Lipoprotein Cholesterol and Metabolic Syndrome.

Background: Prior research has established an association between small dense low-density lipoprotein cholesterol (sdLDL-C) and dyslipidemia, serving as a significant marker for predicting cardiovascular diseases. Nevertheless, the connection between sdLDL-C and metabolic syndrome (MetS) remains unclear. Methods: This study retrospectively analyzed 23,187 individuals who underwent health checkups at Taizhou Hospital's health management center. Here, we investigated the relationship between sdLDL-C and MetS, along with its components, utilizing Spearman correlation analysis, receiver operating characteristic (ROC) curve analysis, logistic regression, and mediation analysis. Results: The MetS group exhibited significantly higher level of sdLDL-C compared to the non-MetS group (P<0.001). We observed a strong correlation between sdLDL-C and several key factors: TG (r = 0.711), TC (r = 0.672), LDL-C (r = 0.781), GGT (r = 0.420), and HDL-C (r = -0.417). After adjusting for age and gender, the odds ratio (OR) (95% confidence interval [CI]) for MetS incidence in the second, third, and fourth quartiles versus the first quartile of sdLDL-C concentration were 2.264 (95% CI: 1.851, 2.770), 4.053 (95% CI: 3.350, 4.903), and 9.034 (95% CI: 7.531, 10.837). The optimal cut-off value for diagnosing MetS using sdLDL-C was determined to be 0.98 mmol/L, with an area under the ROC curve (AUC) of 0.716 (95% CI: 0.705, 0.726). Additionally, mediation analysis revealed that sdLDL-C mediated a 12.8% correlation between GGT and TG concentration. Conclusion: The sdLDL-C is correlated with MetS and it can successfully mediate the relationship between GGT and TG. Our data suggests that sdLDL-c and GGT are suitable parameters for preventing and monitoring MetS.

Construction of a nomogram for predicting compensated cirrhosis with Wilson's disease based on non-invasive indicators.

BACKGROUND: Wilson's disease (WD) often leads to liver fibrosis and cirrhosis, and early diagnosis of WD cirrhosis is essential. Currently, there are few non-invasive prediction models for WD cirrhosis. The purpose of this study is to non-invasively predict the occurrence risk of compensated WD cirrhosis based on ultrasound imaging features and clinical characteristics. METHODS: A retrospective analysis of the clinical characteristics and ultrasound examination data of 102 WD patients from November 2018 to November 2020 was conducted. According to the staging system for WD liver involvement, the patients were divided into a cirrhosis group (n = 43) and a non-cirrhosis group (n = 59). Multivariable logistic regression analysis was used to identify independent influencing factors for WD cirrhosis. A nomogram for predicting WD cirrhosis was constructed using R analysis software, and validation of the model's discrimination, calibration, and clinical applicability was completed. Due to the low incidence of WD and the small sample size, bootstrap internal sampling with 500 iterations was adopted for validation to prevent overfitting of the model. RESULTS: Acoustic Radiation Force Impulse (ARFI), portal vein diameter (PVD), and serum albumin (ALB) are independent factors affecting WD cirrhosis. A nomogram for WD cirrhosis was constructed based on these factors. The area under the ROC curve (AUC) of the model's predictive ability is 0.927 (95% CI: 0.88-0.978). As demonstrated by 500 Bootstrap internal sampling validations, the model has high discrimination and calibration. Clinical decision curve analysis shows that the model has high clinical practical value. ROC curve analysis of the model's rationality indicates that the model's AUC is greater than the AUC of using ALB, ARFI, and PVD alone. CONCLUSION: The nomogram model constructed based on ARFI, PVD, and ALB can serve as a non-invasive tool to effectively predict the risk of developing WD cirrhosis.

Electron beam lithography on nonplanar and irregular surfaces.

E-beam lithography is a powerful tool for generating nanostructures and fabricating nanodevices with fine features approaching a few nanometers in size. However, alternative approaches to conventional spin coating and development processes are required to optimize the lithography procedure on irregular surfaces. In this review, we summarize the state of the art in nanofabrication on irregular substrates using e-beam lithography. To overcome these challenges, unconventional methods have been developed. For instance, polymeric and nonpolymeric materials can be sprayed or evaporated to form uniform layers of electron-sensitive materials on irregular substrates. Moreover, chemical bonds can be applied to help form polymer brushes or self-assembled monolayers on these surfaces. In addition, thermal oxides can serve as resists, as the etching rate in solution changes after e-beam exposure. Furthermore, e-beam lithography tools can be combined with cryostages, evaporation systems, and metal deposition chambers for sample development and lift-off while maintaining low temperatures. Metallic nanopyramids can be fabricated on an AFM tip by utilizing ice as a positive resistor. Additionally, Ti/Au caps can be patterned around a carbon nanotube. Moreover, 3D nanostructures can be formed on irregular surfaces by exposing layers of anisole on organic ice surfaces with a focused e-beam. These advances in e-beam lithography on irregular substrates, including uniform film coating, instrumentation improvement, and new pattern transferring method development, substantially extend its capabilities in the fabrication and application of nanoscale structures.

Anlotinib Inhibits Cisplatin Resistance in Non-Small-Cell Lung Cancer Cells by Inhibiting MCL-1 Expression via MET/STAT3/Akt Pathway.

Background: Anlotinib is an effective targeted therapy for advanced non-small-cell lung cancer (NSCLC) and has been found to mediate chemoresistance in many cancers. However, the underlying molecular mechanism of anlotinib mediates cisplatin (DDP) resistance in NSCLC remains unclear. Methods: Cell viability was assessed by the cell counting kit 8 assay. Cell proliferation, migration, and invasion were determined using the colony formation assay and transwell assay. The mRNA expression levels of mesenchymal-epithelial transition factor (MET) and myeloid cell leukemia-1 (MCL-1) were measured by quantitative real-time PCR. Protein expression levels of MET, MCL-1, and STAT3/Akt pathway-related markers were examined using western blot analysis. Results: Our data showed that anlotinib inhibited the DDP resistance of NSCLC cells by regulating cell proliferation and metastasis. Moreover, MET and MCL-1 expression could be decreased by anlotinib treatment. Silencing of MET suppressed the activity of the STAT3/Akt pathway and MCL-1 expression. Furthermore, MET overexpression reversed the inhibitory effect of anlotinib on the DDP resistance of NSCLC cells, and this effect could be eliminated by MCL-1 knockdown or ACT001 (an inhibitor for STAT3/Akt pathway). Conclusion: Our results confirmed that anlotinib inhibited DDP resistance in NSCLC cells, which might decrease MCL-1 expression via mediating the MET/STAT3/Akt pathway.

Quantitative Analysis of Shear Wave Elastography and US-Guided Diffuse Optical Tomography for Evaluating Biological Characteristics of Breast Cancer.

RATIONALE AND OBJECTIVES: Shear Wave Elastography (SWE) and Ultrasound-guided Diffuse Optical Tomography (US-guided DOT) demonstrate promise in distinguishing between benign and malignant breast lesions. This study aims to assess the feasibility and correlation of SWE and US-guided DOT in evaluating the biological characteristics of breast cancer. MATERIALS AND METHODS: A cohort of 235 breast cancer patients with 238 lesions, scheduled for surgery within one to three days, underwent B-mode ultrasound (US), US-guided DOT, and SWE. Parameters such as Total Hemoglobin Concentration (THC), Maximal Elasticity (Emax), Mean Elasticity (Emean), Standard Deviation of Elasticity (Esd), and Area Ratio were measured. Correlation with post-surgical pathology reports was examined to explore associations between THC, SWE Parameters, and pathology characteristics. RESULTS: Lesions in patient groups with ER-, PR-, HER2 + , high Ki67, LVI+ , and ALN+ exhibited higher THC, Emax, and Esd compared to groups with ER+ , PR+ , HER2-, low Ki67, LVI-, and ALN-. The increase was seen in all grades of IDC-I to -III. THC significantly correlated with Smax (r = 0.340, P < 0.001), Emax (r = 0.339, P < 0.001), Emean (r = 0.201, P = 0.003), and Esd (r = 0.313, P < 0.001). CONCLUSION: US-guided DOT and SWE prove valuable for the quantitative assessment of breast cancer's biological characteristics, with THC positively correlated with Emax, Emean, and Esd.

Remediation of polycyclic aromatic hydrocarbons polluted soil by biochar loaded humic acid activating persulfate: performance, process and mechanisms.

The remediation for polycyclic aromatic hydrocarbons contaminated soil with cost-effective method has received significant public concern, a composite material, therefore, been fabricated by loading humic acid into biochar in this study to activate persulfate for naphthalene, pyrene and benzo(a)pyrene remediation. Experimental results proved the hypothesis that biochar loaded humic acid combined both advantages of individual materials in polycyclic aromatic hydrocarbons adsorption and persulfate activation, achieved synergistic performance in naphthalene, pyrene and benzo(a)pyrene removal from aqueous solution with efficiency reached at 98.2%, 99.3% and 90.1%, respectively. In addition, degradation played a crucial role in polycyclic aromatic hydrocarbons remediation, converting polycyclic aromatic hydrocarbons into less toxic intermediates through radicals of ·SO4-, ·OH, ·O2-, and 1O2 generated from persulfate activation process. Despite pH fluctuation and interfering ions inhibited remediation efficiency in some extent, the excellent performances of composite material in two field soil samples (76.7% and 91.9%) highlighted its potential in large-scale remediation.

The influencing factors for tumor thrombus in patients with hepatocellular carcinoma.

Background: Microvascular invasion (MVI) is considered to be an important factor in the early invasion and metastasis of liver cancer, and the survival rate of patients with MVI is much lower than that of patients without MVI. Therefore, it is crucial to accurately predict the independent predictors of tumor thrombus formation. This study aimed to assess the risk factors for tumor thrombus grades in patients with hepatocellular carcinoma (HCC). Methods: Between August 2011 and December 2022, the data of 231 patients diagnosed with HCC were collected and divided into the following three groups: an MVI-negative group, an MVI-positive group, and a portal vein tumor thrombus (PVTT) group. Univariate analysis was used to compare the differences between the three groups in terms of clinical features, pathology, and imaging features. Multiple logistic regression analysis was used to analyze the risk factors associated with tumor thrombus grades, and the cutoff value was finally calculated by using the receiver operating characteristic (ROC) curve. Results: The incidence of MVI and PVTT in the patients with HCC were 10.0% and 6.1%, respectively; univariate analysis revealed statistically significant differences in tumor diameter, alpha fetoprotein level, Ki-67 expression level, gender, tumor quantity, arteriovenous fistula, peritumoral enhancement, and satellite nodules among the three groups (P<0.05). Multiple logistic regression analysis showed that Ki-67 expression level, tumor diameter, and peritumoral enhancement were independent risk factors for tumor thrombus grades (P<0.05). The area under the curve (AUC) of Ki-67 expression level and tumor diameter was 0.713 [95% confidence interval (CI): 0.626-0.800] and 0.753 (95% CI: 0.669-0.837), respectively, and the AUC of the combination analysis was 0.805 (95% CI: 0.723-0.888), with a cutoff value of 17.5% and 4.1 cm, respectively (P<0.05). Conclusions: Tumor diameter, Ki-67 expression level, and peritumoral enhancement can be used as independent predictors of tumor thrombus in patients with HCC. The combination of tumor diameter and Ki-67 expression level can further improve diagnostic efficacy.

METTL3 modification of circStk4 affects mouse glomerular messangial cell autophagy, proliferation and apotosis by regulating miR-133a-3p/C1 axis.

OBJECTIVE: The study aimed to explore the impact of N6-methyladenosine (m6A) modification in circStk4 on glomerular mesangial cells (GMCs) autophagy, proliferation and apoptosis. METHODS: The interactions between circStk4 and miR-133a-3p, miR-133a-3p and C1 were demonstrated through luciferase reporter assays. The circStk4 localization was analyzed using fluorescence in situ hybridization and nuclear/cytosol fractionation assays. Colorimetric assays, MeRIP-qPCR, and western blot (WB) were employed to confirm the m6A modification of circStk4 and identify the key methylation enzyme. RT-qPCR was conducted to determine the impact of METTL3 on the circStk4 RNA expression. Additionally, CCK-8, flow cytometry, transmission electron microscopy, immunofluorescence, WB and RT-qPCR were employed to investigate the effects of METTL3 or circStk4 on the proliferation, autophagy and apoptosis of GMCs. Enzyme-linked immunosorbent assay was utilized to assess the inflammatory factors. RESULTS: m6A modifications were found in circStk4 and METTL3 was a key methylating enzyme. Furthermore, it was observed that circStk4 competitively bound miR-133a-3p and increased C1 levels. Silencing circStk4 resulted in decreased GMCs proliferation, increased autophagy and apoptosis, and reduced inflammation levels. Additionally, METTL3 played a role in inhibiting GMCs proliferation and promoting autophagy and apoptosis by regulating the circStk4 expression. On verifying the interplay between autophagy, proliferation and apoptosis, and found that the inhibition of autophagy led to an increase in cell proliferation and a decrease in apoptosis. CONCLUSION: m6A modification of circStk4 mediated by METTL3 influenced circStk4 expression and impacted autophagy, proliferation and apoptosis in GMCs via the miR-133a-3p/C1 axis. This discovery introduces a novel therapeutic approach for CGN treatment.

Proximity-Enhanced Functional Imaging Analysis of Engineered Tumors.

Functional imaging (FI) techniques have revolutionized tumor imaging by providing information on specific tumor functions, such as glycometabolism. However, tumor cells lack unique molecular characteristics at the molecular level and metabolic pathways, resulting in limited metabolic differences compared to normal cells and increased background signals from FI. To address this limitation, we developed a novel imaging technique termed proximity-enhanced functional imaging (PEFI) for accurate visualization of tumors. By using "two adjacent chemically labeled glycoproteins" as output signals, we significantly enhance the metabolic differences between tumor and normal cells by PEFI, thereby reducing the background signals for analysis and improving the accuracy of tumor functional imaging. Our results demonstrate that PEFI can accurately identify tumors at the cellular, tissue, and animal level, and has potential value in clinical identification and analysis of tumor cells and tissues, as well as in the guidance of clinical tumor resection surgery.

Tissue distribution of metabolites in Cordyceps cicadae determined by DESI-MSI analysis.

In this paper, we establish an in situ visualization analysis method to image the spatial distribution of metabolites in different parts (sclerotium, coremium) and different microregions of Cordyceps cicadae (C. cicadae) to achieve the in situ visual characterization of tissues for a variety of metabolites such as nucleosides, amino acids, polysaccharides, organic acids, fatty acids, and so on. The study included LC-MS chemical composition identification, preparation of C. cicadae tissue sections, DEDI-MSI analysis, DESI combined with Q-TOF/MS to obtain high-resolution imaging of mass-to-charge ratio and space, imaging of C. cicadae in positive-negative ion mode with a spatial resolution of 100 µm, and localizing and identifying its chemical compositions based on its precise mass. A total of 62 compounds were identified; nucleosides were mainly distributed in the coremium, L-threonine and DL-isoleucine, and other essential amino acids; peptides were mainly distributed in the sclerotium of C. cicadae; and the rest of the amino acids did not have a clear pattern; sugars and sugar alcohols were mainly distributed in the coremium of C. cicadae; organic acids and fatty acids were distributed in the nucleus of C. cicadae more than in the sclerotium, and the mass spectrometry imaging method is established in the research. The mass spectrometry imaging method established in this study is simple and fast and can visualize and analyse the spatial distribution of metabolites of C. cicadae, which is of great significance in characterizing the metabolic network of C. cicadae, and provides support for the quality evaluation of C. cicadae and the study of the temporal and spatial metabolic network of chemical compounds.

Evaluation of the Idylla™ EGFR Mutation Test on formalin-fixed, paraffin-embedded tissue of human lung cancer.

Background: Epidermal growth factor receptor (EGFR) mutation detection is essential for the therapy of lung cancer. A sensitive, specific, and cost-effective standardized method to quickly and accurately detect EGFR mutations is urgently needed. Methods: We evaluated the Idylla™ EGFR Mutation Assay for EGFR mutations in formalin-fixed, paraffin-embedded (FFPE) tumor samples from 232 lung cancer patients, and compared the results with amplification refractory mutation system (ARMS) (n=146) and next-generation sequencing (NGS) (n=86). The surgical tumor sections and cell blocks derived from the same FFPE section were compared. Overall concordance, specificity, sensitivity, cost-effectiveness and turnaround time were compared among the three methods. Results: The overall concordance between Idylla and ARMS was 89.51% [95% confidence interval (CI): 83.31% to 93.64%] and the specificity of Idylla was 88.68% (95% CI: 80.69% to 93.76%). A concordance of 97.67% (95% CI: 91.41% to 99.86%) was obtained between Idylla and NGS, the specificity of Idylla was 96.30% (95% CI: 86.16% to 99.36%). Compared to the ARMS and NGS, the Idylla™ system significantly reduces the turnaround time. Combining labor, equipment, reagents and time costs, Idylla is more affordable. Conclusions: Clinically urgent cases with adequate cellularity, can first perform Idylla to detect critical markers, then perform NGS for a comprehensive mutation analysis. Besides, with limited molecular expertise or infrastructure, the Idylla has the potential to extend EGFR testing to more pathology laboratories in primary hospitals.

Kitchen compost-derived humic acid application promotes ryegrass growth and enhances the accumulation of Cd: An analysis of the soil microenvironment and rhizosphere functional microbes.

Phytoremediation is an environmentally friendly and safe approach for remediating environments contaminated with heavy metals. Humic acid (HA) has high biological activity and can effectively complex with heavy metals. However, whether HA affects available Cd storage and the Cd accumulation ability of plants by altering the soil microenvironment and the distribution of special functional microorganisms remains unclear. Here, we investigated the effects of applying kitchen compost-derived HA on the growth and Cd enrichment capacity of ryegrass (Lolium perenne L.). Additionally, the key role of HA in regulating the structure of rhizosphere soil bacterial communities was identified. HA promoted the growth of perennial ryegrass and biomass accumulation and enhanced the Cd enrichment capacity of ryegrass. The positive effect of HA on the soil microenvironment and rhizosphere bacterial community was the main factor promoting the growth of ryegrass, and this was confirmed by the significant positive correlation between the ryegrass growth index and the content of SOM, AP, AK, and AN, as well as the abundance of rhizosphere growth-promoting bacteria such as Pseudomonas, Steroidobacter, Phenylobacterium, and Caulobacter. HA passivated Cd and inhibited the translocation capacity of ryegrass. The auxiliary effect of resistant bacteria on plants drove the absorption of Cd by ryegrass. In addition, HA enhanced the remediation of Cd-contaminated soil by ryegrass under different Cd levels, which indicated that kitchen compost-derived HA could be widely used for the phytoremediation of Cd-contaminated soil. Generally, our findings will aid the development of improved approaches for the use of kitchen compost-derived HA for the remediation of Cd-contaminated soil.

Transjugular intrahepatic portosystemic shunt for the treatment of hepatic sinusoidal obstruction syndrome caused by pyrrolizidine alkaloids: A multicenter retrospective study.

Purpose: To assess the impact of transjugular intrahepatic portosystemic shunt (TIPS) on clinical outcomes and liver histology in patients with hepatic sinusoidal obstruction syndrome (HSOS) caused by pyrrolizidine alkaloids (PA), and compare these results with those of patients who received supportive treatment alone. Materials and methods: From June 2015 to August 2022, 164 patients diagnosed with PA-HSOS in six tertiary care centers were retrospectively included in this study and divided into TIPS group (n = 69) and supportive treatment (ST) group (n = 95). The main endpoint was to determine whether TIPS placement could improve survival in PA-HSOS patients. The clinical symptoms associated with portal hypertension were also evaluated in this study. Additionally, a small TIPS-subgroup of 7 patients received liver biopsies before and after TIPS for histological analysis. Results: The incidence of death was markedly lower in the TIPS group than in the ST group (log-rank p = 0.026). Multivariate Cox model revealed that group assignment (hazard ratio (HR) 5.146; 95 % confidence interval (CI) 1.587-16.687; p = 0.006), total bilirubin (HR 1.029; 95 % CI 1.020-1.038; p < 0.001), and INR (HR 13.291; 95 % CI 3.637-48.566; p < 0.001) were independent predictors for mortality. In addition, TIPS placement reduced the risk of complications associated with portal hypertension but did not increase the rate of overt hepatic encephalopathy (log-rank p = 0.731). Furthermore, six of 7 TIPS patients receiving liver biopsies improved after TIPS placement, and one patient developed fibrosis. Conclusions: TIPS placement decreased the mortality and risk of complications associated with portal hypertension. Histological evaluation in a few patients showed a potential improvement by TIPS.

Machine learning in the prediction of in-hospital mortality in patients with first acute myocardial infarction.

BACKGROUND: Persistent efforts are required to further reduce the in-hospital mortality of patients suffering from acute myocardial infarction (AMI), even in the face of a global trend of declining AMI-related fatalities. We investigated deep machine learning models for in-hospital death prediction in patients on their first AMI. METHOD: In this 2-center retrospective analysis, first AMI patients from Hospital I and Hospital II were included; 4783 patients from Hospital 1 were split in a 7:3 ratio between the training and testing sets. Data from 1053 AMI patients in Hospital II was used for further validation. 70 clinical information and laboratory examination parameters as predictive indicators were included. Logistic Regression Classifier (LR), Random Forests Classifier (RF), eXtreme Gradient Boosting (XGB), Support Vector Machine Classifier (SVM), Multilayer Perceptron (MLP), Gradient Boosting Machine (GBM), Bootstrapped Aggregation (Bagging) models with AMI patients were developed. The importance of selected variables was obtained through the Shapley Additive exPlanations (SHAP) method. The performance of each model was shown using the area under the receiver operating characteristic curve (AUROC) and the area under the precision-recall curve (Average Precision; AP). RESULT: The in-hospital mortality for AMI in the training, testing, and validation sets were 5.7 %, 5.6 %, and 6.0 %, respectively. The top 8 predictors were D-dimer, brain natriuretic peptide, cardiogenic shock, neutrophil, prothrombin time, blood urea nitrogen, cardiac arrest, and phosphorus. In the testing cohort, the models of LR, RF, XGB, SVM, MLP, GBM, and Bagging yielded AUROC values of 0.929, 0.931, 0.907, 0.868, 0.907, 0.923, and 0.932, respectively. Bagging has good predictive value and certain clinical value in external validation with AUROC 0.893. CONCLUSION: In order to improve the forecasting accuracy of the risk of AMI patients, guide clinical nursing practice, and lower AMI inpatient mortality, this study looked into significant indicators and the optimal models for predicting AMI inpatient mortality.

Effect of soil organic matter-mediated electron transfer on heavy metal remediation: Current status and perspectives.

Soil contamination by heavy metals poses major risks to human health and the environment. Given the current status of heavy metal pollution, many remediation techniques have been tested at laboratory and contaminated sites. The effects of soil organic matter-mediated electron transfer on heavy metal remediation have not been adequately studied, and the key mechanisms underlying this process have not yet been elucidated. In this review, microbial extracellular electron transfer pathways, organic matter electron transfer for heavy metal reduction, and the factors affecting these processes were discussed to enhance our understanding of heavy metal pollution. It was found that microbial extracellular electrons delivered by electron shuttles have the longest distance among the three electron transfer pathways, and the application of exogenous electron shuttles lays the foundation for efficient and persistent remediation of heavy metals. The organic matter-mediated electron transfer process, wherein organic matter acts as an electron shuttle, promotes the conversion of high valence state metal ions, such as Cr(VI), Hg(II), and U(VI), into less toxic and morphologically stable forms, which inhibits their mobility and bioavailability. Soil type, organic matter structural and content, heavy metal concentrations, and environmental factors (e.g., pH, redox potential, oxygen conditions, and temperature) all influence organic matter-mediated electron transfer processes and bioremediation of heavy metals. Organic matter can more effectively mediate electron transfer for heavy metal remediation under anaerobic conditions, as well as when the heavy metal content is low and the redox potential is suitable under fluvo-aquic/paddy soil conditions. Organic matter with high aromaticity, quinone groups, and phenol groups has a stronger electron transfer ability. This review provides new insights into the control and management of soil contamination and heavy metal remediation technologies.

Synergistic mechanism of stir-baked curcumae radix with vinegar in dysmenorrhea rats based on UPLC-Q-TOF/MS metabolomics.

Curcumae Radix (i.e. Huangsiyujin: HSYJ), a well-known traditional Chinese medicine (TCM), has been widely used in clinical practice for many years to treat depression and primary dysmenorrhea. Modern pharmacological researches have demonstrated its anti-inflammatory, antidepressant, and dysmenorrhea relief effects. According to the processing theory of TCM, it is believed that stir-baked HSYJ with vinegar may enhance the ability to disperse stagnant hepatoqi and alleviate pain. However, whether the vinegar concoction of HSYJ can enhance the therapeutic effect on the Qi stagnation due to liver depression (LDQS) type of dysmenorrhea and what its mechanism has not been well explained. Based on the processing drugs theory of "stir-baked with vinegar into liver", a metabolomic approach was used to investigate the therapeutic effect and mechanism of stir-baked HSYJ with vinegar to enhance the treatment of dysmenorrhea in rats. By establishing a rat model of dysmenorrhea of the "LDQS" type, observation of hemorheology, uterine pathological sections, COX-2 and OTR protein expression and other indicators; analysis of urinary metabolic changes in rats by UPLC-Q-TOF-MS technique, to compare the differential biomarkers and metabolic pathways in the treatment of dysmenorrhea due to "liver stagnation and qi stagnation" before and after stir-baked HSYJ with vinegar. Stir-baked HSYJ with vinegar significantly inhibited the writhing response of rats, improved hemorheology, repaired damaged diseased uterus and inhibited high expression of COX-2 and OTR proteins in uterus; 68 differential metabolites were screened from the urine of rats, compared with the raw HSYJ, the levels of 14 metabolites were significantly changed in stir-baked HSYJ with vinegar, involving the pathways of phenylalanine, tyrosine and tryptophan metabolism, cysteine and methionine metabolism, aspartate and glutamate metabolism. The potentiating effect of stir-baked HSYJ with vinegar may be related to the regulation of multiple amino acid metabolic pathways.

Polypeptides from traditional Chinese medicine: Comprehensive review of perspective towards cancer management.

Cancer has always been a focus of global attention, and the difficulty of treatment and poor prognosis have always plagued humanity. Conventional chemotherapeutics and treatment with synthetic disciplines will cause adverse side effects and drug resistance. Therefore, searching for a safe, valid, and clinically effective drug is necessary. At present, some natural compounds have proved to have the potential to fight cancer. Polypeptides obtained from traditional Chinese medicine are good anti-cancer ingredients. The anticancer activity has been fully demonstrated in vivo and in vitro. However, most of the functional studies on traditional Chinese medicine polypeptides are at the stage of basic experimental research, and fewer of them have been applied to clinical trials. Hence, this review mainly discusses the chemical structure, extraction, separation and purification methods, the anti-cancer mechanism, and structure-activity relationships of traditional Chinese medicine polypeptides. It provides theoretical support for strengthening the rapid separation and purification and the overall efficacy and mechanism of action, as well as the industrialization and clinical application of traditional Chinese medicine polypeptides.

Analysis of Immune and Prognostic-Related lncRNA PRKCQ-AS1 for Predicting Prognosis and Regulating Effect in Sepsis.

Background: Sepsis was a high mortality and great harm systemic inflammatory response syndrome caused by infection. lncRNAs were potential prognostic marker and therapeutic target. Therefore, we expect to screen and analyze lncRNAs with potential prognostic markers in sepsis. Methods: Transcriptome sequencing and limma was used to screen dysregulated RNAs. Key RNAs were screened by correlation analysis, lncRNA-mRNA co-expression and weighted gene co-expression network analysis. Immune infiltration, gene set enrichment analysis and gene set variation analysis were used to analyze the immune correlation. Kaplan-Meier curve, receiver operator characteristic curve, Cox regression analysis and nomogram were used to analyze the correlation between key RNAs and prognosis. Sepsis model was established by lipopolysaccharide-induced HUVECs injury, and then cell viability and migration ability were detected by cell counting kit-8 and wound healing assay. The levels of apoptosis-related proteins and inflammatory cytokines were detected by RT-qPCR and Western blot. Reactive Oxygen Species and superoxide dismutase were detected by commercial kit. Results: Fourteen key differentially expressed lncRNAs and 663 key differentially expressed genes were obtained. And these lncRNAs were closely related to immune cells, especially T cell activation, immune response and inflammation. Subsequently, Subsequently, lncRNA PRKCQ-AS1 was identified as the regulator for further investigation in sepsis. RT-qPCR results showed that PRKCQ-AS1 expression was up-regulated in clinical samples and sepsis model cells, which was an independent prognostic factor in sepsis patients. Immune correlation analysis showed that PRKCQ-AS1 was involved in the immune response and inflammatory process of sepsis. Cell function tests confirmed that PRKCQ-AS1 could inhibit sepsis model cells viability and promote cell apoptosis, inflammatory damage and oxidative stress. Conclusion: We constructed immune-related lncRNA-mRNA regulatory networks in the progression of sepsis and confirmed that PRKCQ-AS1 is an important prognostic factor affecting the progression of sepsis and is involved in immune response.

Exploring the mechanism underlying the therapeutic effects of butein in colorectal cancer using network pharmacology and single-cell RNA sequencing data.

BACKGROUND: Butein has shown substantial potential as a cancer treatment, but its precise mechanism of action in colorectal cancer (CRC) remains unclear. This study aimed to uncover the underlying mechanisms through which butein operates in CRC and to identify potential biomarkers through a comprehensive investigation. METHODS: Target genes associated with butein were sourced from SwissTargetPrediction, CTD, BindingDB and TargetNet. Gene expression data from the GSE38026 dataset and the single-cell dataset (GSE222300) were retrieved from the Gene Expression Omnibus database. The activation of disease-related pathways was assessed using Kyoto Encyclopedia of Genes and Genomes, Gene Ontology and differential gene analysis. Disease-associated genes were identified through differential analysis and weighted gene co-expression network analysis (WGCNA). The protein-protein interaction network was utilized to pinpoint potential drug targets. Molecular complex detection (MCODE) analysis was employed to uncover relevant genes influenced by butein within key subgroup networks. Machine learning techniques were applied for the screening of potential biomarkers, with receiver operating characteristic curves used to evaluate their clinical significance. Single-cell analysis was conducted to assess the pharmacological targets of butein in CRC, with validation performed using the external dataset GSE40967. RESULTS: A total of 232 target genes for butein were identified. Functional enrichment analysis revealed significant enrichment of signaling pathways, including mitogen-activated protein kinase, JAK-STAT and NF-κB, among these genes. Differential analysis, in conjunction with WGCNA, yielded 520 disease-related genes. Subsequently, a disease-drug-gene network consisting of 727 targets was established, and a subnetwork containing 56 crucial genes was extracted. Important pathways such as the FoxO signaling pathway exhibited significant enrichment within these key genes. Machine learning applied to the 56 important genes led to the identification of a potential biomarker, UBE2C. Receiver operating characteristic analysis demonstrated the excellent clinical predictive utility of UBE2C. Single-cell analysis suggested that butein's therapeutic effects might be linked to its influence on epithelial and T cells, with UBE2C expression associated with these cell types. Validation using the external dataset GSE40967 further confirmed the exceptional clinical predictive capability of UBE2C. CONCLUSION: This study combines network pharmacology with single-cell analysis to unravel the mechanisms underlying butein's effects in CRC. Notably, UBE2C emerged as a promising biomarker with superior clinical efficacy. These research findings contribute significantly to our understanding of specific molecular mechanisms, potentially shaping future clinical practices.

Development and application of a multiplex PCR method for the simultaneous detection of goose parvovirus, waterfowl reovirus, and goose astrovirus in Muscovy ducks.

A multiplex polymerase chain reaction (PCR) method was developed to detect and distinguish goose parvovirus (GPV), waterfowl reovirus (WRV), and goose astrovirus (GAstV). Three pairs of primers were designed based on conserved regions in the genomic sequences of these enteric viruses and were used to specifically amplify targeted fragments of 493 bp from the viral protein 3 (VP3) gene of GPV, 300 bp from the sigma A-encoding gene of WRV, and 156 bp from the capsid protein-encoding gene of GAstV. The results showed that the primers can specifically amplify target fragments, without any cross-amplification with other viruses, indicating that the method had good specificity. A sensitivity test showed that the detection limit of the multiplex PCR method was 1 × 103 viral copies. A total of 102 field samples from Muscovy ducks with clinically suspected diseases were evaluated using the newly developed multiplex PCR method. The ratio of positive samples to total samples for GPV, WRV, and GAstV was 73.53% (75/102) for multiplex PCR and was 73.53% (75/102) for routine PCR. Seventy-five positive samples were detected by both methods, for a coincidence ratio of 100%. This multiplex PCR method can simultaneously detect GPV, WRV, and GAstV, which are associated with viral enteritis, thereby providing a specific, sensitive, efficient, and accurate new tool for clinical diagnosis and laboratory epidemiological investigations.