Axillary vein as an alternative venous access site for VV-ECMO cannulation: a case report.

BACKGROUND: Ultrasound-guided percutaneous axillary vein cannulation can reduce cannulation failure and mechanical complications, is as safe and effective as internal jugular vein cannulation, and is superior to subclavian vein cannulation using landmark technique. As far, reports of venovenous extracorporeal membrane oxygenation (VV-ECMO) with percutaneous axillary vein cannulation are rare. CASE PRESENTATION: A 64-year-old man presenting with dyspnea and chest tightness after aspirating sewage was admitted to the emergency department. Computed tomography (CT) showed diffuse exudation of both lungs and arterial blood gas analysis showed an oxygenation index of 86. He was diagnosed with aspiration pneumonia-induced acute respiratory distress syndrome (ARDS) and intubated for deteriorated oxygenation. Despite the combination therapy of protective mechanical ventilation and prone position, the patient's oxygenation deteriorated further, accompanied with multiple organ dysfunction syndrome, which indicated the requirement of support with VV-ECMO. However, vascular ultrasound detected multiple thrombus within bilateral internal jugular veins. As an alternative, right axillary vein was chosen as the access site of return cannula. Subsequently, femoral-axillary VV-ECMO was successfully implemented under the ultrasound guidance, and the patient's oxygenation was significantly improved. Unfortunately, the patient died of hyperkalemia-induced ventricular fibrillation after 36 h of VV-ECMO running. Despite the poor prognosis, the blood flow during ECMO run was stable, and we observed no bleeding complication, vascular injury, or venous return disorder. CONCLUSIONS: Axillary vein is a feasible alternative access site of return cannula for VV-ECMO if internal jugular vein access were unavailable.

Unveiling the Chemical Composition of Sulfur-Fumigated Herbs: A Triple Synthesis Approach Using UHPLC-LTQ-Orbitrap MS-A Case Study on Steroidal Saponins in Ophiopogonis Radix.

Ophiopogonis Radix (OR) is a traditional Chinese medicine. In recent years, in order to achieve the purpose of drying, bleaching, sterilizing and being antiseptic, improving appearance, and easy storage, people often use sulfur fumigation for its processing. However, changes in the chemical composition of medicinal herbs caused by sulfur fumigation can lead to the transformation and loss of potent substances. Therefore, the development of methods to rapidly reveal the chemical transformation of medicinal herbs induced by sulfur fumigation can guarantee the safe clinical use of medicines. In this study, a combined full scan-parent ions list-dynamic exclusion acquisition-diagnostic product ions analysis strategy based on UHPLC-LTQ-Orbitrap MS was proposed for the analysis of steroidal saponins and their transformed components in sulfur-fumigated Ophiopogonis Radix (SF-OR). Based on precise mass measurements, chromatographic behavior, neutral loss ions, and diagnostic product ions, 286 constituents were screened and identified from SF-OR, including 191 steroidal saponins and 95 sulfur-containing derivatives (sulfates or sulfites). The results indicated that the established strategy was a valuable and effective analytical tool for comprehensively characterizing the material basis of SF-OR, and also provided a basis for potential chemical changes in other sulfur-fumigated herbs.

Active peptides from Eupolyphaga sinensis walker attenuates experimental hyperlipidemia by regulating the gut microbiota and biomarkers in rats with dyslipidemia.

Eupolyphaga sinensis Walker (ESW) is a traditional Chinese medicine formulation used to treat hyperlipidemia. However, the hypolipidemic effect of the active peptides from E. sinensis Walker (APE) is incompletely understood. We studied the hypolipidemic effect of APE and explored the impact of APE on the gut microbiota (GM) in rats suffering from hyperlipidemia. APE was prepared by enzymatic digestion, and its structure was characterized using various methods. The anti-hyperlipidemic activity of APE was assessed using a high-fat diet (HFD)-induced model in zebrafish and rats. In rats, HFD administration caused abnormalities of lipid metabolism and disturbances of the GM and amino acid (AA) profile in plasma. The abundance of bacteria of the phyla Firmicutes and Bacteroides was increased significantly (p < 0.05), and the relative abundance of Lactobacillus species and Clostridium species was decreased significantly (p < 0.05). HFD therapy affected the levels of 12 AAs in vivo: 10 AAs showed increased levels and two AAs had decreased levels (p < 0.05). Similar results were demonstrated in an experiment on fecal microbiota transplantation. APE treatment dose-dependently decreased lipid factors and liver damage (p < 0.05). Sequencing of the 16 S rRNA gene indicated that APE improved the intestinal-flora structure of rats with HL markedly, and increased the relative abundance of Lactobacillus species and Clostridium species. Metabolomics analysis indicated that APE could alter the levels of 10 AAs affected by HFD consumption. Spearman correlation analysis revealed that gamma-aminobutyric acid (GABA) could be a crucial metabolite, and Lactobacillus species and Clostridium species might be important bacteria for the action of APE against hyperlipidemia. We speculate that APE exhibited an anti-hyperlipidemic effect by regulating GABA synthesis in the presence of Lactobacillus species and Clostridium species.

Untargeted and Targeted Metabolomics Reveal the Active Peptide of Eupolyphaga sinensis Walker against Hyperlipidemia by Modulating Imbalance in Amino Acid Metabolism.

The active peptide (APE) of Eupolyphaga sinensis Walker, which is prepared by bioenzymatic digestion, has significant antihyperlipidemic effects in vivo, but its mechanism of action on hyperlipidemia is not clear. Recent studies on amino acid metabolism suggested a possible link between it and hyperlipidemia. In this study, we first characterized the composition of APE using various methods. Then, the therapeutic effects of APE on hyperlipidemic rats were evaluated, including lipid levels, the inflammatory response, and oxidative stress. Finally, the metabolism-regulating mechanisms of APE on hyperlipidemic rats were analyzed using untargeted and targeted metabolomic approaches. The results showed that APE significantly reduced the accumulation of fat, oxidative stress levels, and serum pro-inflammatory cytokine levels. Untargeted metabolomic analysis showed that the mechanism of the hypolipidemic effect of APE was mainly related to tryptophan metabolism, phenylalanine metabolism, arginine biosynthesis, and purine metabolism. Amino-acid-targeted metabolomic analysis showed that significant differences in the levels of eight amino acids occurred after APE treatment. Among them, the expression of tryptophan, alanine, glutamate, threonine, valine, and phenylalanine was upregulated, and that of arginine and proline was downregulated in APE-treated rats. In addition, APE significantly downregulated the mRNA expression of SREBP-1, SREBP-2, and HMGCR. Taking these points together, we hypothesize that APE ameliorates hyperlipidemia by modulating amino acid metabolism in the metabolome of the serum and feces, mediating the SREBP/HMGCR signaling pathway, and reducing oxidative stress and inflammation levels.

Construction of a prognostic model for colorectal adenocarcinoma based on Zn transport-related genes identified by single-cell sequencing and weighted co-expression network analysis.

Background: Colorectal cancer (CRC) is one of the most prevalent malignancies and the third most lethal cancer globally. The most reported histological subtype of CRC is colon adenocarcinoma (COAD). The zinc transport pathway is critically involved in various tumors, and its anti-tumor effect may be through improving immune function. However, the Zn transport pathway in COAD has not been reported. Methods: The determination of Zn transport-related genes in COAD was carried out through single-cell analysis of the GSE 161277 obtained from the GEO dataset. Subsequently, a weighted co-expression network analysis of the TCGA cohort was performed. Then, the prognostic model was conducted utilizing univariate Cox regression and least absolute shrinkage and selection operator (LASSO) Cox regression analysis. Functional enrichment, immune microenvironment, and survival analyses were also carried out. Consensus clustering analysis was utilized to verify the validity of the prognostic model and explore the immune microenvironment. Ultimately, cell experiments, including CCK-8,transwell and scratch assays, were performed to identify the function of LRRC59 in COAD. Results: According to the Zn transport-related prognostic model, the individuals with COAD in TCGA and GEO databases were classified into high- and low-risk groups. The group with low risk had a comparatively more favorable prognosis. Two groups had significant variations in the immune infiltration, MHC, and the expression of genes related to the immune checkpoint. The cell experiments indicated that the proliferation, migration, and invasion of the HCT-116, DLD-1, and RKO cell lines were considerably increased after LRRC59 knockdown. It proved that LRRC59 was indeed a protective factor for COAD. Conclusion: A prognostic model for COAD was developed using zinc transport-related genes. This model can efficiently assess the immune microenvironment and prognosis of individuals with COAD. Subsequently, the function of LRRC59 in COAD was validated via cell experiments, highlighting its potential as a biomarker.

Thoracic endovascular aortic repair under venoarterial extracorporeal membrane oxygenation for acute aortic dissection patients: a case report.

Background: Open repair and replacement of the diseased aorta is still the standard treatment for type A aortic dissection (TAAD) in most patients. In endovascular treatment alone, ensuring adequate blood supply to the brain while covering the dissection with a stent is difficult. Case presentation: This study includes a 71-year-old male patient with type A aortic dissection presented at a recent follow-up examination after having undergone thoracic endovascular aortic repair (TEVAR) plus left subclavian artery chimney stent reconstruction for descending aortic dissection 5 years ago. Preoperative computed tomographic angiography, computed tomographic perfusion, and transcranial Doppler showed an intact cerebral arterial ring and good collateral circulation. We successfully performed an endovascular repair of the thoracic aorta with venoarterial extracorporeal membrane oxygenation (V-A ECMO) to protect the craniocerebral blood supply, greatly increase the safety of the operation, and ensure a good prognosis. Conclusion: TEVAR under V-A ECMO protection is beneficial for patients with TAAD because of its minimal trauma, rapid recovery, few complications, and low mortality.

USP8 targeted by Mir-874-3p promotes trophoblastic cell invasion by stabilizing the expression of ENaC on trophoblast membrane.

The aim of this study was to investigate the role of ubiquitin-specific peptidase 8 (USP8) in human trophoblast cells and its molecular mechanism. Based on the GSE30186 dataset, USP8 was identified as a downregulated gene in pre-eclampsia (PE). Analysis of clinical samples also revealed that USP8 expression at both the mRNA and protein levels in placental tissue from patients with PE was significantly lower than that from healthy pregnant women. Plate clone formation, scratch-wound healing, Transwell, tubule formation, and western blot assays collectively revealed that USP8 overexpression promoted the proliferation, migration, invasion, and pro-angiogenesis function of trophoblast cells, while USP8 knockdown induced the opposite effects. Bioinformatics analysis and luciferase reporter assay results indicated that the 3' untranslated region of USP8 was targeted by miR-874-3p. USP8 expression in the placental tissue of patients with PE was significantly lower than that of healthy pregnant women. USP8 actively regulated the growth and invasion of human trophoblast cells and stabilized the epithelial sodium channel (ENaC) on the cell membrane. MiR-874 targeted USP8 in the trophoblast cells and upregulation of miR-874-3p resulted in a decrease in the proliferation, migration, invasion, and pro-angiogenesis ability of trophoblast cells. These results indicate that USP8 can reverse the above mentioned negative effects of miR-874-3p on trophoblast cells. USP8 targeted by miR-874-3p facilitates the invasion of trophoblastic cells by stabilizing the expression of the ENaC, which may be a possible therapeutic target for PE.

Stepwise Targeted Matching Strategy for Comprehensive Profiling of Xanthohumol Metabolites In Vivo and In Vitro Using UHPLC-Q-Exactive Orbitrap Mass Spectrometer.

Xanthohumol (XN), a natural prenylated flavonoid extracted and isolated from the hop plant (Humulus lupulus), possesses diverse pharmacological activities. Although the metabolites of XN have been investigated in the previous study, a comprehensive metabolic profile has been insufficient in vivo or in vitro until now. The current study was aimed at systematically elucidating the metabolic pathways of XN after oral administration to rats. Herein, a UHPLC-Q-Exactive Orbitrap MS was adopted for the potential metabolites detection. A stepwise targeted matching strategy for the overall identification of XN metabolites was proposed. A metabolic net (53 metabolites included) on XN in vivo and in vitro, as well as the metabolic profile investigation, were designed, preferably characterizing XN metabolites in rat plasma, urine, liver, liver microsomes, and feces. On the basis of a stepwise targeted matching strategy, the net showed that major in vivo metabolic pathways of XN in rats include glucuronidation, sulfation, methylation, demethylation, hydrogenation, dehydrogenation, hydroxylation, and so on. The proposed metabolic pathways in this research will provide essential data for further pharmaceutical studies of prenylated flavonoids and lay the foundation for further toxicity and safety studies.

Variation in central venous oxygen saturation to evaluate fluid responsiveness: a systematic review and meta-analysis.

BACKGROUND: Since oxygen content and oxygen consumption typically remain unchanged within a short period, variation in central venous oxygen saturation (ΔScvO2) during fluid challenge can theoretically track the changes in cardiac output (CO). We conducted this meta-analysis to systematically assess the diagnostic performance of ΔScvO2 during a fluid challenge for fluid responsiveness in mechanically ventilated patients receiving volume expansion. METHODS: Electronic databases were systematically searched to identify relevant studies published before October 24, 2022. As the cutoff value of ΔScvO2 was expected to vary across the included studies, we estimated the area under the hierarchical summary receiver operating characteristic curve (AUHSROC) as the primary measure of diagnostic accuracy. The optimal threshold of ΔScvO2 and the corresponding 95% confidential interval (CI) were also estimated. RESULTS: This meta-analysis included 5 observational studies comprising 240 participants, of whom 133 (55%) were fluid responders. Overall, the ΔScvO2 during the fluid challenge exhibited excellent performance for defining fluid responsiveness in mechanically ventilated patients receiving volume expansion, with an AUHSROC of 0.86 (95% CI 0.83-0.89), a pooled sensitivity of 0.78 (95% CI 0.69-0.85), a pooled specificity of 0.84 (95% CI 0.72-0.91), and a pooled diagnostic odds ratio of 17.7 (95% CI 5.9-53.2). The distribution of the cutoff values was nearly conically symmetrical and concentered between 3 and 5%; the mean and median cutoff values were 4% (95% CI 3-5%) and 4% (95% CI not estimable), respectively. CONCLUSIONS: In mechanically ventilated patients receiving volume expansion, the ΔScvO2 during the fluid challenge is a reliable indicator of fluid responsiveness. Clinical trial registration PROSPERO, https://www.crd.york.ac.uk/prospero/ , registry number: CRD42022370192.

Comprehensive Study of In vivo and In vitro Metabolites of Cycloastragenol Based on UHPLC-Q-Exactive Orbitrap Mass Spectrometer.

BACKGROUND: Cycloastragenol (CAG) is a sapogenin derived from the main bioactive constituents of Astragali Radix (AR). However, the current research on CAG metabolism in vivo and in vitro is still inadequate, and the metabolite cluster is incomplete due to incomplete analysis strategy. OBJECTIVE: The objective of this study was to screen and identify the metabolic behavior of CAG in vivo and in vitro. METHODS: A simple and rapid analysis strategy based on UHPLC-Q-Exactive Orbitrap mass spectrometry combined with data-mining processing technology was developed and used to screen and identify CAG metabolites in rat body fluids and tissues after oral administration. RESULTS: As a result, a total of 82 metabolites were fully or partially characterized based on their accurate mass, characteristic fragment ions, retention times, corresponding Clog P values, and so on. Among the metabolites, 61 were not been reported in previous reports. These metabolites (6 metabolites in vitro and 91 in vivo) were generated through reactions of hydroxylation, glucuronidation, sulfation, hydrogenation, hydroxylation, demethylation, deisopropylation, dehydroxylation, ring cleavage, and carboxyl substitution and their composite reactions, and the hydroxylation might be the main metabolic reaction of CAG. In addition, the characteristic fragmentation pathways of CAG were summarized for the subsequent metabolite identification. CONCLUSION: The current study not only clarifies the metabolite cluster-based and metabolic regularity of CAG in vivo and in vitro, but also provides ideas for metabolism of other saponin compounds.

Comprehensive Analysis of Pterostilbene Metabolites In Vivo and In Vitro Using a UHPLC-Q-Exactive Plus Mass Spectrometer with Multiple Data-Mining Methods.

Pterostilbene, a stilbene phytoalexin, is mainly obtained from blueberries and grape vines; however, its metabolic mechanisms were unclear in vivo. In the present study, three different methods were used to prepare biological samples, and then, an efficient strategy based on ultrahigh-performance liquid chromatography coupled with mass spectrometry was developed to screen and identify pterostilbene metabolites in rat urine, plasma, liver, and feces. In order to elucidate pterostilbene or its metabolites involved in vitro, this study was assessed by the liver microsome system. As a result, a total of 88 pterostilbene metabolites were characterized. Among them, 77 metabolites in vivo and 14 metabolites in vitro were found; 50 and 38 metabolites were observed in rat plasma and urine, while only 4 and 12 metabolites were detected in rat feces and liver, inferring that plasma and urine possessed more diverse types of pterostilbene metabolites; 41 metabolic products were obtained by solid-phase extraction, and 9 and 10 metabolites were screened by methanol precipitation and acetonitrile precipitation, respectively, indicating that solid-phase extraction could be adopted as the most acceptable method for pterostilbene metabolism. The results also demonstrated that pterostilbene mainly underwent glucosylation, dehydrogenation, hydrogenation, demethoxylation, sulfation, NAC binding, methylene ketogenic, acetylation, and methylation. In summary, this research provides an idea for the further study of drug metabolism.

Identification and mechanism prediction of mulberroside A metabolites in vivo and in vitro of rats using an integrated strategy of UHPLC-Q-Exactive Plus Orbitrap MS and network pharmacology.

Mulberroside A is a polyhydroxylated stilbene active component of Morus alba L. Studies have shown that it has antitussive, antiasthmatic, tyrosinase and antioxidation activities. However, little is known about the metabolism of it in vitro and in vivo. In our study, an integrated strategy on the basis of UHPLC-Q-Exactive Plus Orbitrap MS and network pharmacology was established to comprehensively research the metabolic characteristic of mulberroside A for the first time. Plasma, urine, feces and liver tissues of rats in the blank group and drug group were collected after intragastric administration of mulberroside A at a dose of 150 mg/kg, and rat liver microsomes were cultured for in vitro metabolism experiment. The biological samples were processed by different methods and analyzed in positive and negative ion modes using UHPLC-Q-Exactive Plus Orbitrap MS. A total of 72 metabolites were finally identified based on the accurate molecular mass, retention time, MS/MS spectra and related literatures combined with the Compound Discoverer 3.1. The metabolic pathways were mainly hydrolysis, glucuronidation, hydrogenation, sulfation, hydroxylation, methylation and their composite reactions. In addition, a network pharmacology method was used to predict the mechanism of action of mulberroside A and its metabolites. In the end, 7 metabolites with high gastrointestinal absorption and drug-likeness and 167 targets were screened by Swiss ADME and Swiss Target Prediction. 1702 items of GO analysis and 158 related signaling pathways of KEGG were enriched using Metascape. This study established a novel integrated strategy based on UHPLC-Q-Exactive Plus Orbitrap MS and network pharmacology, which could systematically analyze the metabolism behavior of mulberroside A in vivo and in vitro of rats and provide basis for the further research of mulberroside A.

Active Peptide AR-9 From Eupolyphaga sinensis Reduces Blood Lipid and Hepatic Lipid Accumulation by Restoring Gut Flora and Its Metabolites in a High Fat Diet-Induced Hyperlipidemia Rat.

The dysbiosis of gut flora and its metabolites plays important roles in the progression of hyperlipidemia (HL), and some bioactive peptides are available for HL treatment. In this study, we aimed to isolate an active peptide (AR-9) from active peptides of E. sinensis (APE) and determine whether AR-9 could improve many symptoms of a HL rat induced by a high-fat diet (HFD) by modulating gut flora and its metabolites. Above all, AR-9 was derived from APE using ion-exchange chromatography, and its structure was deconstructed by Fourier transform infrared spectrometer (FT-IR), circular dichroism (CD) spectroscopy, and UHPLC-Q-Exactive-Orbitrap MS. Then, an HFD-induced HL model in SD rats was established and used to clarify the regulatory effects of AR-9 (dose of 3 mg/kg) on HL. Normal diet-fed rats were taken as the control. The plasma samples and liver were harvested for biochemical and histopathological examinations. 16S rRNA gene sequencing and untargeted metabolomics were sequenced to assess changes in gut flora and its metabolites from rat fecal samples. Finally, Spearman's correlation analysis was used to assess the relationship between lipid-related factors, gut flora, and its metabolites so as to evaluate the mechanism of AR-9 against HL. The results of the separation experiments showed that the amino acid sequence of AR-9 was AVFPSIVGR, which was a fragment of the actin protein from Blattaria insects. Moreover, HFD rats developed exaltation of index factors, liver lipid accumulation, and simple fibrosis for 8 weeks, and the profiles of gut flora and its metabolites were significantly altered. After treatment, AR-9 decreased the levels of lipid factors in plasma and the extent of liver damage. 16S rRNA gene sequencing results indicated that AR-9 significantly increased the relative abundance of beneficial bacteria Bacteroidetes and reduced the relative abundance of the obesity-associated bacteria Firmicutes. Furthermore, AR-9 changed gut microbiota composition and increased the relative abundance of beneficial bacteria: Lactobacillus, Clostridium, Dehalobacterium, and Candidatus arthromitus. Fecal metabolomics showed that the pathway regulated by AR-9 was "arginine biosynthesis", in which the contents were citrulline and ornithine. Spearman's correlation analysis revealed that two metabolites (ornithine and citrulline) showed significantly negative correlations with obesity-related parameters and positive correlations with the gut genera (Clostridium) enriched by AR-9. Overall, our results suggested interactions between gut microbial shifts and fecal amino acid/lipid metabolism and revealed the mechanisms underlying the anti-HL effect of AR-9. The abovementioned results not only reveal the initial anti-HL mechanism of AR-9 but also provide a theoretical basis for the continued development of AR-9.

Clinical Utility of the Prenatal Ultrasound Score of the Placenta Combined with Magnetic Resonance Imaging in Diagnosis of Placenta Accreta during the Second and Third Trimester of Pregnancy.

Objective: The aim is to explore the clinical utility of the prenatal ultrasound score of the placenta combined with magnetic resonance imaging (MRI) in diagnosis of placenta accreta during the second and third trimester of pregnancy. Materials and Methods: A total of 108 pregnant women with suspected placenta accreta treated in Wuhan Hankou Hospital and Yantaishan Hospital of Yantai from January 2019 to January 2022 were retrospectively analyzed, the enrolled pregnant women received MRI examination because of suspected results of ultrasonic diagnosis, and by taking pathologic findings as the gold standard, the diagnostic efficacy of the ultrasound score, MRI, and their combination to placenta accreta during the second and third trimester of pregnancy was analyzed, and the diagnostic sensitivity, specificity, the positive predictive value, and the negative predictive value of these diagnostic modalities were evaluated. Results: Among 108 patients with suspected placenta accreta, 75 with pathologically confirmed placenta accreta were included in the accreta group, and 33 without placenta accreta were included in the non-accreta group; no statistical between-group differences in the patients' age, gestational weeks, educational degree, and other general data were observed (P > 0.05), but the history of cesarean section, history of induced abortion, and incidence rate of placenta praevia were significantly higher in the accreta group than in the non-accreta group (P < 0.05); the ultrasound score was significantly higher in the accreta group than in the non-accreta group (P < 0.05); the incidence rates of signs of "placental heterogeneity" and "bulge of lower segment of the uterus and local thickening of the placenta" were obviously higher in the accreta group than in the non-accreta group (P < 0.05); according to the comparison with pathologic findings, the accuracy rate, sensitivity, specificity, the positive predictive value, and the negative predictive value of combined diagnosis were significantly higher than those of single application of the ultrasound score and MRI diagnosis (P < 0.05); and ROC analysis found that the area under the curve of combined diagnosis was obviously larger than that of the ultrasound score and MRI diagnosis (P < 0.05). Conclusion: A combining prenatal ultrasound score of the placenta with MRI plays an important role in the diagnosis of placenta accreta during the second and third trimester of pregnancy, which can further improve the diagnostic accuracy rate of placenta accreta and provide significant guidance in preventing high-risk complications during the perinatal period.

HFE promotes mitotic cell division through recruitment of cytokinetic abscission machinery in hepatocellular carcinoma.

HFE (Hemochromatosis) is a conventional iron level regulator and its loss of function due to gene mutations increases the risk of cancers including hepatocellular carcinoma (HCC). Likewise, studies focusing on HFE overexpression in cancers are all limited to linking up these events as a consequence of iron level deregulation. No study has explored any iron unrelated role of HFE in cancers. Here, we first reported HFE as an oncogene in HCC and its undescribed function on promoting abscission in cytokinesis during mitotic cell division, independent of its iron-regulating ability. Clinical analyses revealed HFE upregulation in tumors linking to large tumor size and poor prognosis. Functionally and mechanistically, HFE promoted cytokinetic abscission via facilitating ESCRT abscission machinery recruitment to the abscission site through signaling a novel HFE/ALK3/Smads/LIF/Hippo/YAP/YY1/KIF13A axis. Pharmacological blockage of HFE signaling axis impeded tumor phenotypes in vitro and in vivo. Our data on HFE-driven HCC unveiled a new mechanism utilized by cancer cells to propel rapid cell division. This study also laid the groundwork for tumor intolerable therapeutics development given the high cytokinetic dependency of cancer cells and their vulnerability to cytokinetic blockage.

[UHPLC-Q-Exactive Orbitrap MS/MS-based rapid identification of chemical components in substance benchmark of Kaixin San].

Ultra-performance liquid chromatography-quadrupole-electrostatic field Orbitrap mass spectrometry(UHPLC-Q-Exactive Orbitrap MS/MS) was used for rapid identification of the chemical components in Kaixin San substance benchmark. The gradient elution was performed through a Waters ACQUITY~(TM) BEH C_(18) column(2.1 mm×150 mm, 1.7 µm) with water-acetonitrile as mobile phase, a column temperature of 30 ℃, a flow rate of 0.3 mL·min~(-1), and a sample size of 1 µL. The scanning was performed in the negative ion mode. The complex component groups in Kaixin San substance benchmark were quickly and accurately identified and clearly assigned based on the comparison of the retention time and MS data with those of the reference substance as well as the relative molecular weight of the same or similar components in the mass spectrum database and literature. A total of 77 compounds were identified, including 26 saponins, 13 triterpenoid acids, 20 oligosaccharide esters, 5 xanthones, and 13 other compounds. The qualitative method established in this study can systematically, accurately, and quickly identify the chemical components in Kaixin San substance benchmark, which can provide a basis for the further analysis of its active components in vivo and the establishment of its quality control system.

Nurses' experience of work stress related to COVID-19 regular prevention and control in China: A qualitative study.

AIM: To explore the experiences of nurses' work stress related to COVID-19 regular epidemic prevention and control in China. BACKGROUND: The global COVID-19 epidemic is still severe, and China's ongoing regular epidemic prevention and control still cannot be relaxed, which places demands on nurses. METHODS: Thirty nurses and eight nurse managers were interviewed using semistructured in-depth interviews, and the data were analysed by the Colaizzi seven-step analysis method. RESULTS: Four themes were extracted as follows: environmental factors, organizational factors, personal factors and positive factors in coping with stress. CONCLUSIONS: Nursing managers should pay attention to construction of the first-line departments of regular epidemic prevention and control. The shortage of nurses' human resources and the increase of nurse-patient conflicts are problems that need to be solved urgently. In addition, this research also emphasizes the importance of promoting nurses' stress-related growth and thinking about the possibility of reform. IMPLICATIONS FOR NURSING MANAGEMENT: The construction of the hospital environment and increasing the resilience of nursing teams require attention. We should attach importance to the training of nurses' communication skills and provide sufficient organizational support and economic guarantees for nurses. Finally, perhaps we should also consider whether it is necessary to reform the relevant hospital systems and how to reform them.

Characterization of Metabolites of α-mangostin in Bio-samples from SD Rats by UHPLC-Q-exactive Orbitrap MS.

BACKGROUND: α-mangostin, a typical xanthone, often exists in Garcinia mangostana L. (Clusiaceae). α-mangostin was found to have a wide range of pharmacological properties. However, its specific metabolic route in vivo remains unclear, while these metabolites may accumulate to exert pharmacological effects, too. OBJECTIVE: This study aimed to clarify the metabolic pathways of α-mangostin after oral administration to the rats. METHODS: Here, an UHPLC-Q-Exactive Orbitrap MS was used for the detection of potential metabolites formed in vivo. A new strategy for the identification of unknown metabolites based on typical fragmentation routes was implemented. RESULTS: A total of 42 metabolites were detected, and their structures were tentatively identified in this study. The results showed that major in vivo metabolic pathways of α-mangostin in rats included methylation, demethylation, methoxylation, hydrogenation, dehydrogenation, hydroxylation, dehydroxylation, glucuronidation, and sulfation. CONCLUSIONS: This study is significant to expand our knowledge of the in vivo metabolism of α-mangostin and to understand the mechanism of action of α-mangostin in rats in vivo.

Comprehensive Identification of Astilbin Metabolites in Rats Based on Multiple Metabolite Templates Combined with UHPLC-Q-Exactive Mass Spectrometry.

BACKGROUND: Astilbin, a dihydroflavonoid compound widely found in plants, exhibits a variety of pharmacological activities and biological effects. However, little is known about the metabolism of this active compound in vivo, which is very helpful for elucidating the pharmacodynamic material basis and application of astilbin. OBJECTIVE: To establish a rapid profiling and identification method for metabolites in rat urine, faeces and plasma using a UHPLC-Q-Exactive mass spectrometer in negative ion mode. METHODS: In this study, a simple and rapid systematic strategy and 7 metabolite templates, which were established based on previous reports, were utilized to screen and identify astilbin metabolites. RESULTS: As a result, a total of 71 metabolites were detected and characterized, among which 32 metabolites were found in rat urine, while 27 and 38 metabolites were characterized from rat plasma and faeces, respectively. These metabolites were presumed to be generated through ring cleavage, sulfation, dehydrogenation, methylation, hydroxylation, glucuronidation, dehydroxylation and their composite reactions. CONCLUSION: This study illustrated the capacity of the sensitive UHPLC-Q-Exactive mass spectrometer analytical system combined with the data-mining methods to rapidly elucidate the unknown metabolism. Moreover, the comprehensive metabolism study of astilbin provided an overall metabolic profile, which will be of great help in predicting the in vivo pharmacokinetic profiles and understanding the action mechanism of this active ingredient.

MRCKß links Dasm1 to actin rearrangements to promote dendrite development.

Proper dendrite morphogenesis and synapse formation are essential for neuronal development and function. Dasm1, a member of the immunoglobulin superfamily, is known to promote dendrite outgrowth and excitatory synapse maturation in vitro. However, the in vivo function of Dasm1 in neuronal development and the underlying mechanisms are not well understood. To learn more, Dasm1 knockout mice were constructed and employed to confirm that Dasm1 regulates dendrite arborization and spine formation in vivo. We performed a yeast two-hybrid screen using Dasm1, revealing MRCKß as a putative partner; additional lines of evidence confirmed this interaction and identified cytoplasmic proline-rich region (823-947 aa) of Dasm1 and MRCKß self-activated kinase domain (CC1, 410-744 aa) as necessary and sufficient for binding. Using co-immunoprecipitation assay, autophosphorylation assay, and BS3 cross-linking assay, we show that Dasm1 binding triggers a change in MRCKß's conformation and subsequent dimerization, resulting in autophosphorylation and activation. Activated MRCKß in turn phosphorylates a class 2 regulatory myosin light chain, which leads to enhanced actin rearrangement, causing the dendrite outgrowth and spine formation observed before. Removal of Dasm1 in mice leads to behavioral abnormalities. Together, these results reveal a crucial molecular pathway mediating cell surface and intracellular signaling communication to regulate actin dynamics and neuronal development in the mammalian brain.