Comprehensive overview of different medicinal parts from Morus alba L.: chemical compositions and pharmacological activities.

Morus alba L., a common traditional Chinese medicine (TCM) with a centuries-old medicinal history, owned various medicinal parts like Mori folium, Mori ramulus, Mori cortex and Mori fructus. Different medical parts exhibit distinct modern pharmacological effects. Mori folium exhibited analgesic, anti-inflammatory, hypoglycemic action and lipid-regulation effects. Mori ramulus owned anti-bacterial, anti-asthmatic and diuretic activities. Mori cortex showed counteraction action of pain, inflammatory, bacterial, and platelet aggregation. Mori fructus could decompose fat, lower blood lipids and prevent vascular sclerosis. The main chemical components in Morus alba L. covered flavonoids, phenolic compounds, alkaloids, and amino acids. This article comprehensively analyzed the recent literature related to chemical components and pharmacological actions of M. alba L., summarizing 198 of ingredients and described the modern activities of different extracts and the bioactive constituents in the four parts from M. alba L. These results fully demonstrated the medicinal value of M. alba L., provided valuable references for further comprehensive development, and layed the foundation for the utilization of M. alba L.

Semantic uncertainty Guided Cross-Transformer for enhanced macular edema segmentation in OCT images.

Macular edema, a prevalent ocular complication observed in various retinal diseases, can lead to significant vision loss or blindness, necessitating accurate and timely diagnosis. Despite the potential of deep learning for segmentation of macular edema, challenges persist in accurately identifying lesion boundaries, especially in low-contrast and noisy regions, and in distinguishing between Inner Retinal Fluid (IRF), Sub-Retinal Fluid (SRF), and Pigment Epithelial Detachment (PED) lesions. To address these challenges, we present a novel approach, termed Semantic Uncertainty Guided Cross-Transformer Network (SuGCTNet), for the simultaneous segmentation of multi-class macular edema. Our proposed method comprises two key components, the semantic uncertainty guided attention module (SuGAM) and the Cross-Transformer module (CTM). The SuGAM module utilizes semantic uncertainty to allocate additional attention to regions with semantic ambiguity, improves the segmentation performance of these challenging areas. On the other hand, the CTM module capitalizes on both uncertainty information and multi-scale image features to enhance the overall continuity of the segmentation process, effectively minimizing feature confusion among different lesion types. Rigorous evaluation on public datasets and various OCT imaging device data demonstrates the superior performance of our proposed method compared to state-of-the-art approaches, highlighting its potential as a valuable tool for improving the accuracy and reproducibility of macular edema segmentation in clinical settings, and ultimately aiding in the early detection and diagnosis of macular edema-related diseases and associated retinal conditions.

Arene-Arene Coupled Disulfamethazines (or Sulfadiazine)-Phenanthroline-Metal(II) Complexes were Synthesized by In Situ Reactions and Inhibited the Growth and Development of Triple-Negative Breast Cancer through the Synergistic Effect of Antiangiogenesis, Anti-Inflammation, Pro-Apoptosis, and Cuproptosis.

The novel metal(II)-based complexes HA-Cu, HA-Co, and HA-Ni with phenanthroline, sulfamethazine, and aromatic-aromatic coupled disulfamethazines as ligands were synthesized and characterized. HA-Cu, HA-Co, and HA-Ni all showed a broad spectrum of cytotoxicity and antiangiogenesis. HA-Cu was superior to HA-Co and HA-Ni, and even superior to DDP, showing significant inhibitory effect on the growth and development of tripe-negative breast cancer in vivo and in vitro. HA-Cu exhibited observable synergistic effects of antiproliferation, antiangiogenesis, anti-inflammatory, pro-apoptosis, and cuproptosis to effectively inhibited tumor survival and development. The molecular mechanism was confirmed that HA-Cu could downregulate the expression of key proteins in the VEGF/VEGFR2 signaling pathway and the expression of inflammatory cytokines, enhance the advantage of pro-apoptotic protein Bax, and enforce cuproptosis by weakening the expression of FDX1 and enhancing the expression of HSP70. Our research will provide a theoretical and practical reference for the development of metal-sulfamethazine and its derivatives as chemotherapy drugs for cancer treatment.

Edge-Guided Contrastive Adaptation Network for Arteriovenous Nicking Classification Using Synthetic Data.

Retinal arteriovenous nicking (AVN) manifests as a reduced venular caliber of an arteriovenous crossing. AVNs are signs of many systemic, particularly cardiovascular diseases. Studies have shown that people with AVN are twice as likely to have a stroke. However, AVN classification faces two challenges. One is the lack of data, especially AVNs compared to the normal arteriovenous (AV) crossings. The other is the significant intra-class variations and minute inter-class differences. AVNs may look different in shape, scale, pose, and color. On the other hand, the AVN could be different from the normal AV crossing only by slight thinning of the vein. To address these challenges, first, we develop a data synthesis method to generate AV crossings, including normal and AVNs. Second, to mitigate the domain shift between the synthetic and real data, an edge-guided unsupervised domain adaptation network is designed to guide the transfer of domain invariant information. Third, a semantic contrastive learning branch (SCLB) is introduced and a set of semantically related images, as a semantic triplet, are input to the network simultaneously to guide the network to focus on the subtle differences in venular width and to ignore the differences in appearance. These strategies effectively mitigate the lack of data, domain shift between synthetic and real data, and significant intra- but minute inter-class differences. Extensive experiments have been performed to demonstrate the outstanding performance of the proposed method.

Research on heart rate extraction method based on mobile phone video.

As an important indicator of human health, heart rate is related to the diagnosis of cardiovascular diseases. In recent years, extracting the heart rate from the mobile phone image has become a research hotspot. However, the illumination intensity of the background, frame rate of the video, and resolution of the image influence heart rate detection accuracy. To overcome these problems, this study proposed a novel heart rate extraction method based on mobile video. Firstly, the mobile phone camera is engaged to record the finger video, the region of interest (ROI) is extracted through the iterative threshold, and the pulse signal is obtained according to the grayscale change of the resolution within the ROI. Then, a low-pass and a high-pass Butterworth filters are exploited to filter out the noise and interframes from the extracted pulse signal. Finally, an improved adaptive peak extraction algorithm is proposed to detect the pulse peaks and the heart rate derived from the difference in pulse peaks. The experimental results show that light intensity, frame rate and resolution all have an influence on the heart rate extraction accuracy, with the most obvious influence of light, the average accuracy of the experiment can reach 99.32 % under good lighting conditions, while only 72.23 % under poor lighting conditions. In terms of frame rate, increasing the frame rate from 30 fps to 60 fps, the accuracy is improved by 0.9 %. For the resolution, increasing the resolution from 1080 p to 2160 p, the accuracy is improved by 1.12 %. While comparing the proposed method with existing methods, the proposed method has a higher accuracy rate, which has important practical value and application prospects in telemedicine and daily monitoring.

An integrated process by ultrasonic enhancement in the deep eutectic solvents system for extraction and separation of chlorogenic acid from Eucommia ulmoides leaves.

This study established an integrated process for the extraction and enrichment of chlorogenic acid(CGA)from Eucommia ulmoides leaves in a deep eutectic solvent system via ultrasonic wave-enhanced adsorption and desorption practices utilizing macroporous resins. Although deep eutectic solvents (DESs) have the advantages of chemical stability, good dissolving capacity, and nonvolatilization, routine solvent recovery operations are not suitable for subsequent separation in this solvent system. Based on the above characteristics, this study integrated the extraction and enrichment processes, in which DESs extracts directly loaded onto the macroporous adsorption resin, avoiding the loss of target components in solvent recovery and redissolution processes. The screening results of solvents and resin types further showed that choline chloride-malic acid (1:1) was the optimal DES, and the NKA-II resin had high adsorption and elution performance for CGA. The viscosities of the DESs were much higher than those of water and conventional organic solvents; thus, the mass transfer resistance was large, which could also affect the adsorption behaviour of the macroporous resin. The thermal and mechanical effects of ultrasound could effectively enhance the efficiency of the mass transfer, adsorption, and desorption in the DES systems. When compared to no sonication treatment, the CGA adsorption at various ultrasonic powers (120-600 W) was examined. At optimal ethanol concentration (60%), the effect of the ultrasonic treatment on the recovery of the DESs (water eluting process) and the desorption capability of CGA were confirmed. The use of three volumes of water elution could recover the DESs without loss of CGA. The adsorption process significantly differed depending on the ultrasonic settings, and the absorption balance time and experimental adsorption capacity at equilibrium were enhanced. Additionally, the adsorption procedure of the NKA-II macroporous resin for CGA under ultrasonic treatment could be clarified by the pseudo second order kinetic equation and the Freundlich isotherm model. Thermodynamic and dynamic parameters indicated that physical adsorption was the main process of the entire procedure, and it was a spontaneous, exothermic, and entropy-reducing physical adsorption process. This study potentially indicates that the use of ultrasonication, as a high-efficiency, environmentally friendly method, can enhance the features of the macroporous resin to better purify target chemicals from a DES extract.

Non-imaging method for angle measurement based on an axicon.

A new non-imaging angle measurement method based on an axicon is proposed in this paper. This method uses an axicon that can form a complex light spot with a clear edge and rich feature information after total internal reflection and refraction on the sloped face compared with convergent lenses, which can only form a blurry edge spot. According to the high sensitivity of the beam transformation of the axicon to the incident angle, light spot images with obvious feature variation can be easily obtained to achieve angle measurement with high accuracy. The method based on an axicon can meet the application requirements of multiple angle measurement ranges, and the structure is simple and compact. In the small-angle measurement experiment combined with a telescope module, the measurement resolution can reach 1 ' ' , the mean absolute error is 0.0010°, and the relative error is within 0.25% in the measurement range of 1.6°.

Rapid Limit Test of Eight Quinolone Residues in Food Based on TLC-SERS, a New Limit Test Method.

Residual quinolones in food that exceed their maximum residue limit (MRL) are harmful to human health. However, the existing methods used for testing these residues have limitations; so, we developed a new limit test method called TLC-SERS to rapidly determine the levels of residues of the following: enrofloxacin (A), ciprofloxacin (B), ofloxacin (C), fleroxacin (D), sparfloxacin (E), enoxacin (F), gatifloxacin (G), and nadifloxacin (H). The residues ware preliminarily separated via TLC. The tested compounds' position on a thin-layer plate were labeled using their relative Rf under 254 nm ultraviolet light, and an appropriate amount of nanometer silver solution was added to the position. The silver on the plate was irradiated with a 532 nm laser to obtain the SERSs of the compounds. The results show significant differences in the SERS of the eight quinolones: the LODs of H, A, D, E, C, G, F, and B were 9.0, 12.6, 8.9, 19.0, 8.0, 8.7, 19.0, and 12.6 ng/mL, respectively; and the RSD was ≤4.9% for the SERS of each quinolone. The limit test results of 20 samples are consistent with those obtained via UPLC-MS/MS. The results indicate that TLC-SERS is a specific, sensitive, stable, and accurate method, providing a new reference for the rapid limit test of harmful residues in foods.

High-Throughput Phytochemical Unscrambling of Flowers Originating from Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) P. K. Hsiao and Astragalus membranaceus (Fisch.) Bug. by Applying the Intagretive Plant Metabolomics Method Using UHPLC-Q-TOF-MS/MS.

Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) P. K. Hsiao (MO) and Astragalus membranaceus (Fisch.) Bug. (ME) are two primary sources of the Astragalus herb, also known as "Huangqi" in China, which is widely applied to treat hypertension, glomerulonephritis, ischemic heart disease, and diabetes mellitus. As two different sources of the Astragalus herb, the chemical profiles of MO and ME may be different. Previous studies showed abundant differences in chemical composition between MO and ME. Therefore, the by-products of MO and ME, such as Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) P. K. Hsiao flower (MOF) and Astragalus membranaceus (Fisch.) Bug. flower (MEF), may have different phytochemical profiles. In this paper, a metabolomics method combined with ultra-high-performance liquid chromatography and electrospray ionization/quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS) was employed to analyze the components of MOF and MEF. Consequently, the results of principal component analysis (PCA) showed that MOF and MEF could be separated clearly. In total, 31 chemical markers differentiating MOF and MEF were successfully identified, including 22 flavonoids, 8 isoflavones and 1 benzopyran. Among them, the contents of 18 components, including Calycosin, Cyanidin-3-O-glucoside, Quercetin, Rutin, Kaempferol, Formononetin, Isomucronulatol and Prim-O-glucosylcimifugin in MEF, were significantly higher than in MOF. In turn, the contents of another 13 components, covering Biochanin A, Tectoridin, Isomucronulatol-7-O-glucoside, Liquiritin, Rhamnetin, etc., were lower in the MEF group than that in the MOF group. It is worth noting that flavonoids, especially flavonoid glycosides, were the primary active chemical ingredients in MOF and MEF. The 18 ingredients in MEF with a higher level carried out diverse activities, like anti-oxidant, anti-inflammatory, anti-bacterial and anti-tumor activities, which led us to speculate that MEF may have greater pharmacological effects and potential development prospects than MOF. The present results displayed that the contents of ingredients in the two different species of plants were radically different, and there was significant uniqueness to the components of MOF and MEF. Our study not only provides helpful chemical information for further quality assessment and active mechanism research of MOF and MEF but also offers scientific support for the resource utilization of MOF and MEF.

Modulatory Effects of Co-Fermented Pu-erh Tea with Aqueous Corn Silk Extract on Gut Microbes and Fecal Metabolites in Mice Fed High-Fat Diet.

Pu-erh tea is recognized for its weight loss effects, but its potential association with gut microbiota and metabolites remains unclear. This research explored the alterations in gut flora and metabolite composition upon treatment with a co-fermented Pu-erh tea with an aqueous corn silk extract (CPC) in obese mice by employing integrated 16S ribosomal RNA gene sequencing and untargeted metabolomics processes. For 8 weeks, mice were fed control, high-fat, and high-fat diets which included a 46 mg/mL CPC extract. The CPC extract the alleviated high-fat diet (HFD), it stimulated systemic chronic inflammation, and it reduced the body weight, daily energy consumption, and adipose tissue weight of the mice. It also modified the gut microbiota composition and modulated the Lactobacillus, Bifidobacterium, Allobaculum, Turicibacter, and Rikenella genera. Fecal metabolomics analysis revealed that the CPC extract influenced the caffeine, cysteine, methionine, tryptophan, biotin metabolism pathways, primary bile acid, and steroid biosynthesis. This research revealed that the CPC extract could inhibit HFD-stimulated abnormal weight gain and adipose tissue accumulation in mice, and modulate mice gut microbiota composition and multiple metabolic pathways.

Density-oriented deep eutectic solvent-based system for the selective separation of polysaccharides from Astragalus membranaceus var. Mongholicus under ultrasound-assisted conditions.

The water extraction and ethanol precipitation method is an extraction method based on the solubility characteristics of polysaccharides that offers wide applicability in the extraction and separation of plant polysaccharides. However, this method leads to large amounts of proteins, nucleic acids, pigments, and other impurities in the polysaccharides products, which makes downstream purification complicated and time-consuming. In this study, a green, high-density natural deep eutectic solvents was used for the high-purity extraction and separation of polysaccharides from Astragalus membranaceus (Fisch) Bge. var. Mongholicus (Bge.) Hsiao roots under ultrasound-assisted conditions. In this study, 16 different natural deep eutectic solvents were designed to screen the best solvent for extracting Astragalus polysaccharides (APSs). Based on the yield and recovery of APSs, a natural deep eutectic solvents composed of choline chloride and oxalic acid with a molar ratio of 1:2 was selected. The related factors affecting polysaccharides extraction and solvent precipitation were investigated. To improve the operating methodology, single-factor trials, a Plackett-Burman design, and a Box-Behnken design were used. The optimal extraction process conditions were obtained as follows: water content of 55%, liquid-solid ratio of 24 mL/g, ultrasonic irradiation time of 54 min, ultrasonic irradiation temperature of 50 °C, ultrasonic irradiation power of 480 W, ethanol precipitation time of 24 h, and ethanol concentration of 75%. Under optimal extraction conditions, the recovery of APSs was 61.4 ± 0.6 mg/g. Considering the special matrix characteristics of A. membranaceus var. Mongholicus roots, physical-technology-based ultrasonic waves promote penetration, and the mass transfer function also solves the bottleneck of high-viscosity deep eutectic solvents in the extraction stage. In comparison with the conventional method, the proposed method based on deep eutectic solvents isolation can significantly increase APSs recovery, which is beneficial to simplifying the process of polysaccharides purification by using solvent properties to separate extracts and reduce impurities in APSs.

A fast sample entropy for pulse rate variability analysis.

Sample entropy is an effective nonlinear index for analyzing pulse rate variability (PRV) signal, but it has problems with a large amount of calculation and time consumption. Therefore, this study proposes a fast sample entropy calculation method to analyze the PRV signal according to the microprocessor process of data updating and the principle of sample entropy. The simulated data and PRV signal are employed as experimental data to verify the accuracy and time consumption of the proposed method. The experimental results on simulated data display that the proposed improved sample entropy can improve the operation rate of the entropy value by a maximum of 47.6 times and an average of 28.6 times and keep the entropy value unchanged. Experimental results on PRV signal display that the proposed improved sample entropy has great potential in the real-time processing of physiological signals, which can increase approximately 35 times.

Corrigendum on: A life-threatening arrhythmia detection method based on pulse rate variability analysis and decision tree.

[This corrects the article DOI: 10.3389/fphys.2022.1008111.].

Effect of stigma maydis polysaccharide on the gut microbiota and transcriptome of VPA induced autism model rats.

Stigma maydis polysaccharide (SMPS) is a plant polysaccharide that participates in immune regulation and gastrointestinal motility. Autism spectrum disorder (ASD) refers to a group of neurodevelopmental disorders, and ASD patients often present intestinal microflora imbalance problems; however, there is no effective treatment method. This study explores the effect of SMPS intervention on the gut microbiota in autism model rats as well as the potential action pathways. Female Wistar rats were intraperitoneally injected with sodium valproic acid (VPA) or normal saline at embryonic day 12.5 to establish an autism model or normal control in their offspring. The offspring prenatally exposed to VPA were randomly assigned to the VPA and the SMPS groups. The SMPS group was administered SMPS from E0.5 to postnatal day (PND) 21. We performed 16S rRNA and transcriptomics analyses to reveal the gut microbiota (GM) and differentially expressed genes in the autism model rats in response to SMPS intervention. SMPS intervention significantly improved the diversity and structure of the GM in autism model rats compared with the VPA rats. Moreover, the relative abundance of Prevotellaceae and Lachnospiraceae_NK4A136_group was increased after SMPS intervention. Transcriptome sequencing showed that 496 differentially expressed genes (DEGs) were identified after SMPS administration compared with the VPA group. Meanwhile, gene ontology (GO) enrichment analysis of DEGs was showed that the SMPS group had significant 653 GO terms. SMPS intervention had a major influence on oxidative phosphorylation, retrograde endocannabinoid signaling, thermogenesis, ribosome, protein digestion and absorption, renin-angiotensin system, calcium signaling pathway, glycosphingolipid biosynthesis-ganglio series, and propanoate metabolism pathways. Overall, this study suggests that SMPS interventions in early life may have an impact on gut microbiota, and then affect the transcriptomics levels of the hippocampal tissue in the VPA-induced autism model rats. It provides scientific evidence for the role of the microbe-gut-brain axis in ASD research.

Relationship between MTHFR C677T, homocysteine, and ischemic stroke in a large sample of the Han Chinese population.

Ischemic stroke, one of the prevalent causes of death and disability worldwide, is linked to environmental and genetic factors, including polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene involved in homocysteine metabolism. The present study aimed to explore the relationship between the MTHFR C677T variant, plasma homocysteine, and risk of developing large-artery atherosclerotic ischemic stroke (LAAIS) among Han Chinese. A population-based case-control study, which included 1810 patients with LAAIS and 1765 unrelated control subjects, was conducted. Compared to the controls, LAAIS patients had a significantly higher prevalence of hypertension, diabetes mellitus, smoking, and alcohol consumption (P < .001), as well as significantly higher mean fasting blood glucose, triglyceride, total cholesterol, and plasma homocysteine levels (P < .001). The TT homozygous genotype correlated with increased risk of developing LAAIS, as indicated by a significantly higher odds ratio (OR) compared to the CT and CC genotypes, in both additive (OR = 3.215, P = .01) and recessive models (OR = 3.265, P = .01). The plasma homocysteine level was genotype-dependent according to the following trend: TT > CT > CC. In conclusion, our data demonstrate that, in spite of its low prevalence in both patients and controls (1.5% vs 0.8%), the MTHFR C677T variant could, at least in part, affect homocysteine levels and this, either alone or in combination with other factors, increases the risk of LAAIS.

A life-threatening arrhythmia detection method based on pulse rate variability analysis and decision tree.

Extreme bradycardia (EB), extreme tachycardia (ET), ventricular tachycardia (VT), and ventricular flutter (VF) are the four types of life-threatening arrhythmias, which are symptoms of cardiovascular diseases. Therefore, in this study, a method of life-threatening arrhythmia recognition is proposed based on pulse rate variability (PRV). First, noise and interference are wiped out from the arterial blood pressure (ABP), and the PRV signal is extracted. Then, 19 features are extracted from the PRV signal, and 15 features with highly important and significant variation were selected by random forest (RF). Finally, the back-propagation neural network (BPNN), extreme learning machine (ELM), and decision tree (DT) are used to build, train, and test classifiers to detect life-threatening arrhythmias. The experimental data are obtained from the MIMIC/Fantasia and the 2015 Physiology Net/CinC Challenge databases. The experimental results show that the DT classifier has the best average performance with accuracy and kappa coefficient (kappa) of 98.76 ± 0.08% and 97.59 ± 0.15%, which are higher than those of the BPNN (accuracy = 94.85 ± 1.33% and kappa = 89.95 ± 2.62%) and ELM (accuracy = 95.05 ± 0.14% and kappa = 90.28 ± 0.28%) classifiers. The proposed method shows better performance in identifying four life-threatening arrhythmias compared to existing methods and has potential to be used for home monitoring of patients with life-threatening arrhythmias.

The association between ST8SIA2 gene and behavioral phenotypes in children with autism spectrum disorder.

Objective: ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 2 (ST8SIA2) encodes a type II membrane protein that is thought to catalyze the transfer of sialic acid (SA) from CMP-SA to N-linked oligosaccharides and glycoproteins. Some population and animal studies have indicated an association between the ST8SIA2 gene and autism spectrum disorder (ASD). However, there is limited information on the correlation between ST8SIA2 and autistic behavioral symptoms. Methods: In this study, 69 ASD and 76 normal control children who were age- and sex-matched were recruited. ST8SIA2 expression and methylation levels were measured by reverse transcription quantitative real-time PCR and pyrosequencing, respectively, and the behavioral phenotypes of ASD children were assessed. Results: The ASD group had lower ST8SIA2 gene expression levels than the control group [t (0.05/2,143) = 2.582, p = 0.011]. Moreover, ST8SIA2 expression levels were positively correlated with daily life skills (r s = 0.381, p = 0.008) and negatively associated with stereotyped behaviors in the ASD group (r s = -0.510, p = 0.004). The methylation levels of the Chr. 15: 92984625 and Chr. 15: 92998561 sites of the ST8SIA2 gene in ASD children were higher than those of controls. The Chr. 15: 92984625 site was positively correlated with the stereotyped behaviors of ASD children (r s = 0.41, p = 0.039). Conclusion: This study provides a scientific basis to elucidate the relationship between the ST8SIA2 gene and behavioral phenotypes of ASD.

Modulation of gut microbiota and fecal metabolites by corn silk among high-fat diet-induced hypercholesterolemia mice.

Corn silk (CS) is known to reduce cholesterol levels, but its underlying mechanisms remain elusive concerning the gut microbiota and metabolites. The aim of our work was to explore how altered gut microbiota composition and metabolite profile are influenced by CS intervention in mice using integrated 16S ribosomal RNA (rRNA) sequencing and an untargeted metabolomics methodology. The C57BL/6J mice were fed a normal control diet, a high-fat diet (HFD), and HFD supplemented with the aqueous extract of CS (80 mg/mL) for 8 weeks. HFD-induced chronic inflammation damage is alleviated by CS extract intervention and also resulted in a reduction in body weight, daily energy intake as well as serum and hepatic total cholesterol (TC) levels. In addition, CS extract altered gut microbial composition and regulated specific genera viz. Allobaculum, Turicibacter, Romboutsia, Streptococcus, Sporobacter, Christensenella, ClostridiumXVIII, and Rikenella. Using Spearman's correlation analysis, we determined that Turicibacter and Rikenella were negatively correlated with hypercholesterolemia-related parameters. Fecal metabolomics analysis revealed that CS extract influences multiple metabolic pathways like histidine metabolism-related metabolites (urocanic acid, methylimidazole acetaldehyde, and methiodimethylimidazoleacetic acid), sphingolipid metabolism-related metabolites (sphinganine, 3-dehydrosphinganine, sphingosine), and some bile acids biosynthesis-related metabolites including chenodeoxycholic acid (CDCA), lithocholic acid (LCA), ursodeoxycholic acid (UDCA), and glycoursodeoxycholic acid (GUDCA). As a whole, the present study indicates that the modifications in the gut microbiota and subsequent host bile acid metabolism may be a potential mechanism for the antihypercholesterolemic effects of CS extract.

WASH regulates the oxidative stress Nrf2/ARE pathway to inhibit proliferation and promote apoptosis of HeLa cells under the action of Jolkinolide B.

Jolkinolide B (JB), a diterpenoid compound isolated from the roots of Euphorbia fischeriana, has gained research attention for its antitumor effects. In recent years, JB reportedly displayed anti-tumor activity in solid tumors, such as breast, ovarian, and prostate cancer, and leukemia. In this study, we evaluated the effect of JB on HeLa cells with a focus on cell growth inhibition and related mechanisms. HeLa cells were cultured in vitro and divided into a blank control group, HeLa-Scramble (0, 0.25, 0.5 mM), and Wiskott-Aldrich syndrome protein and SCAR homolog (WASH) protein silenced group, HeLa-shWASH (0, 0.25, 0.5 mM). Morphological changes were observed using an inverted microscope. The inhibition rate of cell proliferation was detected using the WST-1 method. Flow cytometry Brdu+PI double standard method was used to detect cell replication ability and FITC+PI double standard method was used to detect cell apoptosis rate. Western blot was used to verify the expression of Nrf2, HO-1, WASH, Bax, Bcl-2, and PCNA. The mRNA expression of cytokines (IL-1α, IL-6, and IL-8) was detected using RT-qPCR. The results showed that JB induced cell apoptosis and arrested cells at the G2/M phase in HeLa-shWASH cells compared with HeLa-Scramble cells (P < 0.05, P < 0.01, respectively). In addition, JB upregulated IL-1α, IL-6, and IL-8 in HeLa-shWASH cells. We conclude that WASH protein participates in JB-induced regulation of the Nrf2/ARE pathway, aggravates inflammatory responses, and promotes cancer cell apoptosis, thus inhibiting the proliferation and invasion abilities of HeLa cells. JB may have anti-tumor effects and potential clinical value for the treatment of cervical cancer.

SNTA1-deficient human cardiomyocytes demonstrate hypertrophic phenotype and calcium handling disorder.

BACKGROUND: α-1-syntrophin (SNTA1), a protein encoded by SNTA1, is highly expressed in human cardiomyocytes. Mutations in SNTA1 are associated with arrhythmia and cardiomyopathy. Previous research on SNTA1 has been based on non-human cardiomyocytes. This study was designed to identify the phenotype of SNTA1-deficiency using human cardiomyocytes. METHODS: SNTA1 was knocked out in the H9 embryonic stem cell line using the CRISPR-Cas9 system. H9SNTA1KO cells were then induced to differentiate into cardiomyocytes using small molecule inhibitors. The phenotypic discrepancies associated with SNTA1-deficient cardiomyocytes were investigated. RESULTS: SNTA1 was truncated at the 149th amino acid position of PH1 domain by a stop codon (TGA) using the CRISPR-Cas9 system. SNTA1-deficiency did not affect the pluripotency of H9SNTA1KO, and they retain their in vitro ability to differentiate into cardiomyocytes. However, H9SNTA1KO derived cardiomyocytes exhibited hypertrophic phenotype, lower cardiac contractility, weak calcium transient intensity, and lower level of calcium in the sarcoplasmic reticulum. Early treatment of SNTA1-deficient cardiomyocytes with ranolazine improved the calcium transient intensity and cardiac contractility. CONCLUSION: SNTA1-deficient cardiomyocytes can be used to research the etiology, pathogenesis, and potential therapies for myocardial diseases. The SNTA1-deficient cardiomyocyte model suggests that the maintenance of cardiac calcium homeostasis is a key target in the treatment of myocardial-related diseases.