microRNA-181a-5p promotes fibroblast differentiation of mesenchymal stem cells in rats with pelvic floor dysfunction.

The use of stem cells capable of multilineage differentiation in treating Pelvic Floor Dysfunction (PFD) holds great promise since they are susceptible to entering connective tissue of various cell types and repairing damaged tissues. This research investigated the effect of microRNA-181a-5p (miR-181a-5p) on Bone Marrow Mesenchymal Stem Cells (BMSCs) in rats with PFD. BMSCs were transfected and analyzed for their fibroblast differentiation ability. miR-181a-5p, MFN1, and fibroblast-related genes were quantitatively analyzed. Whether MFN1 is a target gene of miR-181a-5p was predicted and confirmed. The efficacy of BMSCs in vivo rats with PFD was evaluated by measuring Leak Point Pressure (LPP), Conscious Cystometry (CMG), hematoxylin and eosin staining, and Masson staining. The present results discovered that miR-181a-5p was up-regulated and MFN1 was down-regulated during the differentiation of BMSCs into fibroblasts. Fibroblast differentiation of BMSCs was promoted after miR-181a-5p was induced or MFN1 was suppressed, but it was suppressed after miR-181a-5p was silenced. miR-181a-5p improved LPP and conscious CMG outcomes in PDF rats by targeting MFN1 expression, thereby accelerating fibroblast differentiation of BMSCs. In brief, miR-181a-5p induces fibroblast differentiation of BMSCs in PDF rats by MFN1, potentially targeting PDF therapeutics.

The different roles of V-ATPase a subunits in phagocytosis/endocytosis and autophagy.

Microglia are specialized macrophages responsible for the clearance of dead neurons and pathogens by phagocytosis and degradation. The degradation requires phagosome maturation and acidification provided by the vesicular- or vacuolar-type H+-translocating adenosine triphosphatase (V-ATPase), which is composed of the cytoplasmic V1 domain and the membrane-embedded Vo domain. The V-ATPase a subunit, an integral part of the Vo domain, has four isoforms in mammals. The functions of different isoforms on phagosome maturation in different cells/species remain controversial. Here we show that mutations of both the V-ATPase Atp6v0a1 and Tcirg1b/Atp6v0a3 subunits lead to the accumulation of phagosomes in zebrafish microglia. However, their mechanisms are different. The V-ATPase Atp6v0a1 subunit is mainly distributed in early and late phagosomes. Defects of this subunit lead to a defective transition from early phagosomes to late phagosomes. In contrast, The V-ATPase Tcirg1b/Atp6v0a3 subunit is primarily located on lysosomes and regulates late phagosome-lysosomal fusion. Defective Tcirg1b/Atp6v0a3, but not Atp6v0a1 subunit leads to reduced acidification and impaired macroautophagy/autophagy in microglia. We further showed that ATP6V0A1/a1 and TCIRG1/a3 subunits in mouse macrophages preferentially located in endosomes and lysosomes, respectively. Blocking these subunits disrupted early-to-late endosome transition and endosome-to-lysosome fusion, respectively. Taken together, our results highlight the essential and conserved roles played by different V-ATPase subunits in multiple steps of phagocytosis and endocytosis across various species.Abbrevations: Apoe: apolipoprotein E; ANXA5/annexin V: annexin A5; ATP6V0A1/a1: ATPase H+-transporting V0 subunit a1; ATP6V0A2/a2: ATPase H+-transporting V0 subunit a2; ATP6V0A4/a4: ATPase H+-transporting V0 subunit a4; dpf: days post-fertilization; EEA1: early endosome antigen 1; HOPS: homotypic fusion and protein sorting; LAMP1: lysosomal associated membrane protein 1; Lcp1: lymphocyte cytosolic protein 1 (L-plastin); Map1lc3/Lc3: microtubule-associated protein 1 light chain 3; NR: neutral red; PBS: phosphate-buffered saline; PtdIns: phosphatidylinositol; PtdIns3P: phosphatidylinositol-3-phosphate; PtdIns(3,5)P2: phosphatidylinositol (3,5)-bisphosphate; RAB4: RAB4, member RAS oncogene family; RAB5: RAB5, member RAS oncogene family; RAB7: RAB7, member RAS oncogene family; TCIRG1/Atp6v0a3/a3: T cell immune regulator 1, ATPase H+-transporting V0 subunit a3; V-ATPase: vacuolar-type H+-translocating adenosine triphosphatase; Xla.Tubb2b/NBT: tubulin beta 2B class IIb.

[Installed strategy and clinical observation of self-made extracorporeal membrane oxygenation system in the treatment of critically ill patients].

OBJECTIVE: To summarize the strategy and method for the treatment of critically ill patients with self-made extracorporeal membrane oxygenation (ECMO) system. METHODS: A observative study was conducted. Fifty-six patients with ECMO assisted support in Fuwai Central China Cardiovascular Disease Hospital from December 2020 to December 2021 were enrolled. According to the clinical situation of the patients and the wishes of the family, conventional ECMO package (conventional group) or self-made ECMO package (self-made group) was chosen. In the conventional group, the disposable ECMO package was used to install the machine, pre charge and exhaust the air. In the self-made group, the disposable consumables commonly used in extracorporeal circulation during cardiac surgery (including centrifugal pump heads, membrane oxygenation, tubes, connectors, etc.) were used to create a self-made ECMO system. Based on the patient's situation, personalized tube model selection and length control were carried out. The preparation time, auxiliary time, auxiliary method, total pre charge volume, free hemoglobin (FHb) levels after 2 hours of ECMO operation and operating costs, as well as changes in hemodynamics, arterial blood gas analysis, and blood indicators within 48 hours after ECMO placement in the two groups were recorded. The occurrence of adverse events related to the ECMO system during ECMO adjuvant therapy in two groups was simultaneously observed. RESULTS: Fifty-six patients were enrolled finally, with 28 cases in the conventional group and 28 cases in the self-made group, and all successfully completed the operation of ECMO. There was no statistically significant difference in ECMO system preparation time, auxiliary time, auxiliary method, and FHb levels after 2 hours of ECMO operation between the conventional group and the self-made group [preparation time (minutes): 13±4 vs. 15±5, auxiliary time (hours): 287±34 vs. 276±42, veno-arterial ECMO (cases): 22 vs. 24, veno-venous ECMO (cases): 6 vs. 4, FHb after 2 hours of ECMO operation (mg/L): 226±67 vs. 253±78, all P > 0.05]. However, the total pre charge volume and operating costs in the self-made group were significantly lower than those in the conventional group [total pre charge volume (mL): 420±25 vs. 650±10, operating costs (ten thousand yuan): 3.8±0.4 vs. 6.7±0.3, both P < 0.01]. The hemodynamics, arterial blood gas analysis, and blood indicators of patients in the two groups were relatively stable within 48 hours after ECMO operation, and most of the indicators between the two groups showed no statistically significant differences. The hemoglobin (Hb) levels at 12, 24, and 48 hours after the machine transfer in the self-made group were significantly higher than those in the conventional group (g/L: 128.5±23.7 vs. 117.5±24.3 at 12 hours, 121.3±31.3 vs. 109.6±33.2 at 24 hours, 118.5±20.1 vs. 105.2±25.7 at 48 hours, all P < 0.05). Both groups of patients did not experience any adverse event related to the ECMO system, such as membrane pulmonary infiltration, joint detachment, and massive hemolysis, during the ECMO assisted treatment process. CONCLUSIONS: When implementing ECMO for critically ill patients in clinical practice, a self-made ECMO system with disposable consumables commonly used in extracorporeal circulation during cardiac surgery can be used for cardiopulmonary function assistance support, thereby saving patients medical costs and alleviating their dependence on disposable ECMO package in clinical practice.

Shouhui Tongbian Capsule in treatment of constipation: Treatment and mechanism development.

Constipation is common in the diseases of the digestive system in clinics. With the change in diet structure and the increase in life pressure, the prevalence rate increases year by year. In traditional Chinese medicine (TCM), the location of the disease of constipation is in the large intestine, which is related to the dysfunction of lung, spleen, liver, kidney and other viscera. Its pathogenesis is conductive dysfunction of large intestine. Based on the theory, Shouhui Tongbian Capsule (SHTB) is composed of eight traditional Chinese medicines, including Polygoni multiflori Radix (Heshouwu in Chinese), Aloe (Luhui in Chinese), Cassiae Semen (Juemingzi in Chinese), Ginseng Radix et Rhizoma (Renshen in Chinese), Lycii Fructus (Gouqizi in Chinese), Asini Corii Colla (Ejiao in Chinese), Aurantii Fructus Immaturus (Zhishi in Chinese), and Atractylodis Macrocephalae Rhizoma (Baizhu in Chinese), which could help to release excessive turbid, and nourishing yin and supplementing qi in the treatment. This study has been carried out to review the latest advances of SHTB in the treatment of constipation. The results showed that significant effect of SHTB was found in the treatment of constipation, such as functional constipation, and constipation associated with tumor chemotherapy, colitis, type 2 diabetes and chronic cardiac failure. Besides, obvious adverse reactions were not observed. SHTB could effectively treat five types of constipation, provide direction for the future exploration of SHTB in the treatment of other types of constipation.

A comprehensive review of bupleuri radix and its bioactive components： with a major focus on treating chronic liver diseases.

ETHNOPHARMACOLOGICAL RELEVANCE: Bupleuri Radix (BR) has been recognized as an essential herbal medicine for relieving liver depression for thousands of years. Contemporary research has provided compelling evidence of its pharmacological effects, including anti-inflammatory, immunomodulatory, metabolic regulation, and anticancer properties, positioning it as a promising treatment option for various liver diseases. Hepatitis, steatohepatitis, cirrhosis, and liver cancer are among the prevalent and impactful liver diseases worldwide. However, there remains a lack of comprehensive systematic reviews that explore the prescription, bio-active components, and underlying mechanisms of BR in treating liver diseases. AIM OF THE REVIEW: To summarize the BR classical Chinese medical prescription and ingredients in treating liver diseases and their mechanisms to inform reference for further development and research. MATERIALS AND METHODS: Literature in the last three decades of BR and its classical Chinese medical prescription and ingredients were collated and summarized by searching PubMed, Wiley, Springer, Google Scholar, Web of Science, CNKI, etc. RESULTS: BR and its classical prescriptions, such as Xiao Chai Hu decoction, Da Chai Hu decoction, Si Ni San, and Chai Hu Shu Gan San, have been utilized for centuries as effective therapies for liver diseases, including hepatitis, steatohepatitis, cirrhosis, and liver cancer. BR is a rich source of active ingredients, such as saikosaponins, polysaccharides, flavonoids, sterols, organic acids, and so on. These bioactive compounds exhibit a wide range of beneficial effects, including anti-inflammatory, antioxidant, immunomodulatory, and lipid metabolism regulation. However, it is important to acknowledge that BR and its constituents can also possess hepatotoxicity, which is associated with cytochrome P450 (CYP450) enzymes and oxidative stress. Therefore, caution should be exercised when using BR in therapeutic applications to ensure the safe and appropriate utilization of its potential benefits while minimizing any potential risks. CONCLUSIONS: To sum up, BR, its compounds, and its based traditional Chinese medicine are effective in liver diseases through multiple targets, multiple pathways, and multiple effects. Advances in pharmacological and toxicological investigations of BR and its bio-active components in the future will provide further contributions to the discovery of novel therapeutics for liver diseases.

RAD54B promotes gastric cancer cell migration and angiogenesis via the Wnt/ß-catenin pathway.

BACKGROUND: Gastric cancer is an epidemic malignancy that is commonly diagnosed at the late stage. Evidence has elucidated that RAD54B exerts a crucial role in the progress of various tumors, but its specific role and mechanism in gastric cancer remain gloomy. MATERIALS AND METHODS: The level of RAD54B was detected by western blot. RAD54B expression was downregulated or upregulated in both MKN45 and AGS cells by the transfection of shRAD54B or overexpression plasmid, respectively. The role of RAD54B in the growth, migration, invasion and tube formation of gastric cancer was evaluated by Edu, colony formation, transwell and tube formation assays. In addition, the molecular mechanism of RAD54B in gastric cancer was also determined by western blot. Moreover, in vivo experiment was conducted in xenografted mice. RESULTS: The expression of RAD54B was discovered to be upregulated in gastric cancer based on the ATGC and GEPIA databases, which was also confirmed in gastric cancer cell lines. Moreover, overexpression of RAD54B enhanced the growth, migration, invasion, tube formation and Wnt/ß-catenin signaling axis in AGS and MKN45 cells. As expected, knockdown of RAD54B in AGS and MKN45 cells reversed these promotions. More importantly, in vivo assay also verified that RAD54B accelerated the growth of gastric cancer and Wnt/ß-catenin signaling pathway. CONCLUSIONS: Both loss-of-function and gain-of-function assays demonstrated that RAD54B facilitated gastric cancer cell progress and angiogenesis through the Wnt/ß-catenin axis.

Delayed sternal Mycobacterium tuberculosis infection after left ventricular assist device implantation: A case report.

The incidence of Mycobacterium tuberculosis (Mtb) infection in patients with mechanical circulatory support devices is extremely rare. We present a case involving a 38-year-old male who experienced a delayed sternal Mtb infection following left ventricular assist device (LVAD) implantation. More than 5 months post-surgery, the patient was readmitted to the hospital presenting a subxiphoid abscess. The incision site displayed an unsatisfactory healing process after the incision and drainage of the abscess. Despite engaging in a rigorous treatment protocol, which included anti-infective therapy, vacuum-assisted closure, and surgical debridement, the patient's wound remained unhealed. Ultimately, after pus gene sequencing confirmed the diagnosis, the patient was administered a regimen combining anti-tuberculosis and anti-infective therapy, which culminated in the successful healing of the wound. This singular case study not only reveals the clinical progression of an unexpected Mtb infection post-implantation but also emphasizes the challenges encountered in diagnosis and management.

Dynamic interactions between E-cadherin and Ankyrin-G mediate epithelial cell polarity maintenance.

E-cadherin is an essential cell‒cell adhesion protein that mediates canonical cadherin-catenin complex formation in epithelial lateral membranes. Ankyrin-G (AnkG), a scaffold protein linking membrane proteins to the spectrin-based cytoskeleton, coordinates with E-cadherin to maintain epithelial cell polarity. However, the molecular mechanisms governing this complex formation and its relationships with the cadherin-catenin complex remain elusive. Here, we report that AnkG employs a promiscuous manner to encapsulate three discrete sites of E-cadherin by the same region, a dynamic mechanism that is distinct from the canonical 1:1 molar ratio previously described for other AnkG or E-cadherin-mediated complexes. Moreover, we demonstrate that AnkG-binding-deficient E-cadherin exhibited defective accumulation at the lateral membranes and show that disruption of interactions resulted in cell polarity malfunction. Finally, we demonstrate that E-cadherin is capable of simultaneously anchoring to AnkG and ß-catenin, providing mechanistic insights into the functional orchestration of the ankyrin-spectrin complex with the cadherin-catenin complex. Collectively, our results show that complex formation between E-cadherin and AnkG is dynamic, which enables the maintenance of epithelial cell polarity by ensuring faithful targeting of the adhesion molecule-scaffold protein complex, thus providing molecular mechanisms for essential E-cadherin-mediated complex assembly at cell‒cell junctions.

SASH1: A Novel Eph Receptor Partner and Insights into SAM-SAM Interactions.

The Eph (erythropoietin-producing human hepatocellular) receptor family, the largest subclass of receptor tyrosine kinases (RTKs), plays essential roles in embryonic development and neurogenesis. The intracellular Sterile Alpha Motif (SAM) domain presents a critical structural feature that distinguishes Eph receptors from other RTKs and participates in recruiting and binding downstream molecules. This study identified SASH1 (SAM and SH3 domain containing 1) as a novel Eph receptor-binding partner through SAM-SAM domain interactions. Our comprehensive biochemical analyses revealed that SASH1 selectively interacts with Eph receptors via its SAM1 domain, displaying the highest affinity for EphA8. The high-resolution crystal structure of the EphA8-SASH1 complex provided insights into the specific intermolecular interactions between these proteins. Cellular assays confirmed that EphA8 and SASH1 co-localize and co-precipitate in mammalian cells, with cancer mutations (EphA8 R942H or G978D) impairing this interaction. We demonstrated that SAM-SAM interaction is critical for SASH1-mediated regulation of EphA8 kinase activity, shedding new light on the Eph signaling pathway and expanding our understanding of the molecular basis of the tumor suppressor gene SASH1.

Recent Progress in Extracellular Vesicle-Based Carriers for Targeted Drug Delivery in Cancer Therapy.

Extracellular vesicles (EVs) are small, membrane-based vesicles released by cells that play a critical role in various physiological and pathological processes. They act as vehicles for transporting a variety of endogenous cargo molecules, enabling intercellular communication. Due to their natural properties, EVs have emerged as a promising "cell-free therapy" strategy for treating various diseases, including cancer. They serve as excellent carriers for different therapeutics, including nucleic acids, proteins, small molecules, and other nanomaterials. Modifying or engineering EVs can improve the efficacy, targeting, specificity, and biocompatibility of EV-based therapeutics for cancer therapy. In this review, we comprehensively outline the biogenesis, isolation, and methodologies of EVs, as well as their biological functions. We then focus on specific applications of EVs as drug carriers in cancer therapy by citing prominent recent studies. Additionally, we discuss the opportunities and challenges for using EVs as pharmaceutical drug delivery vehicles. Ultimately, we aim to provide theoretical and technical support for the development of EV-based carriers for cancer treatment.

Bacterial outer membrane vesicles-cloaked modified zein nanoparticles for oral delivery of paclitaxel.

To improve the aqueous solubility and oral bioavailability of paclitaxel (PTX), a biomimetic system for oral administration of PTX was efficiently developed as an outer membrane vesicle (OMVs) of sodium caseinate (CAS) modified zein nanoparticles (OMVs-Zein-CAS-PTX-NPs) by Escherichia coli. To verify their structure and properties, the designed nanostructures were thoroughly characterized using various characterization techniques. The results indicated that hydrogen bonds and van der Waals forces mainly drove the interaction between PTX and Zein, but the complex is unstable. The physicochemical stability of PTX-loaded zein nanoparticles was improved by the addition of CAS. The biological characteristics of biofilms are reproduced by nanoparticles cloaked with outer membrane vesicles. OMVs-Zein-CAS-PTX-NPs delayed the release of PTX under simulated gastric and intestinal fluids due to OMVs protection. OMVs-Zein-CAS-PTX-NPs exhibited remarkable antitumor ability in vitro and improved the bioavailability of oral administration of PTX in vivo. Therefore, OMVs cloaked in nanoparticles may be a suitable delivery vehicle to provide an efficient application prospect for the oral administration of PTX.

Efficacy and safety of Shouhui Tongbian Capsules in the treatment of constipation: A systematic review and meta-analysis.

BACKGROUND: Constipation is a common gastrointestinal disorder, which has seriously affected the quality of people's daily life. Traditional Chinese Medicine (TCM) therapy takes syndrome differentiation and treatment as the theoretical guidance with certain advantages in treating constipation with the holistic approach. However, there are few studies on the treatment of constipation with Shouhui Tongbian Capsules (SHTB). PURPOSE: This study was aimed to evaluate the clinical effect and safety of SHTB in the treatment of constipation and provide evidence-based references for clinical application. STUDY DESIGN: A systematic review and meta-analysis of existing literature on SHTB for treating constipation. METHODS: Chinese databases (China Network Knowledge Infrastructure, Wan Fang Database and Chinese Scientific Journal Database) and English databases (PubMed, EmBase and the Cochrane Library) were thoroughly investigated through screening randomized controlled trials on SHTB for constipation from the establishment of all databases to September 26, 2022. Data extraction and quality evaluation were performed on the literature that met the inclusion criteria and a meta-analysis was performed for selected data using Review Manager 5.4, ROB 2.0 and Stata 17.0. RESULTS: A total of 14 RCTs (randomized controlled trial) including 1310 participants were included in the analysis. The results showed that the test group was superior to the control group in improving the total effective rate and curative effect, clinical symptom score, gastrointestinal peptide index and reducing adverse reactions and recurrence rate. The specific results were as follows: ① The total effective rate increased significantly (RR = 1.24, 95% CI [1.18, 1.30], Z = 8.25, p< 0.00001); ② The clinical symptom indexs, including the difficulty of defecation [SMD = -1.28, 95% CI (-1.44, -1.12), Z = 15.65, p< 0.00001], the frequency of spontaneous defecation [SMD = 1.28, 95% CI (1.01, 1.54), Z = 9.52, p< 0.00001], defecation interval [SMD = -1.47, 95% CI (-1.68, -1.26), Z = 13.79, p < 0.00001], incomplete defecation [SMD = -1.34, 95% CI (-1.57, -1.11), Z = 11.42, p < 0.00001], duration of defecation [SMD = -2.02, 95% CI (-2.39, -1.65), Z = 10.73, p < 0.00001], stool characteristics [SMD = -2.30, 95% CI (-2.60, -1.99), Z = 14.72, p< 0.00001] and TCM main syndrome scores [SMD = -1.25, 95% CI (-1.46, -1.05), Z = 11.79, p< 0.00001] increased observably; ③ The gastrointestinal peptide hormone indexs, including MTL Level [SMD = 0.43, 95% CI (0.24, 0.62), Z = 4.44, p < 0.00001] and SP Level [RR =0.57, 95% CI (0.37, 0.87), Z = 2.61, p = 0.009] were improved obviously; ④ The incidence of adverse reactions (RR = 0.57, 95% CI [0.37, 0.87], Z = 2.61, p = 0.009) and recurrence rate (RR = 0.31, 95% CI [0.18, 0.54], Z = 4.28, P <0.001) reduced significantly. Sensitivity analysis showed that there was no significant change in all outcome indicators, which suggested that the results of meta-analysis were relatively stable. Funnel plot and Egger test results showed that the literature included in the study might have publication bias. CONCLUSION: SHTB can be used to treat functional constipation, especially elderly functional constipation, constipation caused by tumor chemotherapy and disease concomitant constipation. The optimal dosage of SHTB was 0.70 g (2 capsules) each time, 3 times a day, for 28 days. Combined with basic treatment, lactose oral solution, mosaic or castor oil could improve the total effective rate, clinical symptom indicators, gastrointestinal peptide hormone indicators and reduce adverse reaction rate of patients. However, due to the limitations of the included clinical trials, high-quality clinical trials with long follow ups are needed to evaluate the effectiveness and safety of SHTB in treating different types of constipation.

Si-Ni-SAN ameliorates obesity through AKT/AMPK/HSL pathway-mediated lipolysis: Network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Si-Ni-San (SNS) is a famous Chinese herbal formula used in China for thousands of years. It has clinical effects on a variety of lipid metabolism disorders, but the ameliorating effects of SNS on obesity and underlying mechanisms remained poorly elucidated. AIM OF THE STUDY: This study aims to explore the therapeutic effect and mechanism of SNS on obesity from multiple perspectives in vitro and in vivo. MATERIALS AND METHODS: The high-fat diet (HFD)-induced obesity mouse model was established to evaluate the effect of SNS. Then network pharmacologic methods were performed to predict underlying mechanisms, and the core pathways were verified in animal and cell studies. RESULTS: Our results demonstrated that SNS significantly reduced body weight, body fat content, white adipose tissue (WAT) expansion in obese mice, and lipid accumulation in primary mouse embryonic fibroblasts (MEFs) cells. Network pharmacologic analysis identified 66 potential therapeutic targets, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of these genes revealed that the most important signaling pathway includes AMP-activated protein kinase (AMPK) signaling pathway, regulation of lipolysis in adipocytes, lipid and atherosclerosis. Western blot assay confirmed that SNS activated hormone-sensitive triglyceride lipase (HSL) and adipose triglyceride lipase (ATGL) activity and promoted lipolysis through AMPK signaling pathway. CONCLUSION: The results confirmed that SNS improves lipid accumulation through AKT/AMPK/HSL axis mediated lipolysis, which opens a new option for clinical treatment of obesity and associated complications.

Peak Blood Lactate at 24 h after ECMO Can Predict 30-day Mortality in Infants after Complex Cardiac Surgery.

OBJECTIVE: Peak blood lactate at 24 h after extracorporeal membrane oxygenation (ECMO) can predict 30-day mortality in infants after complex cardiac surgery. METHODS: Twenty-eight infants with ECMO after complex congenital heart disease surgery were selected from March 2019 to March 2022 in our hospital. The infants were divided into survival group (n = 11) and non-survival group (n = 17) according to 30-day survival after discharge from hospital. The risk factors at 30-day mortality after discharge were analyzed by Cox regression analysis. RESULTS: When compared to the non-survival group, there were significant differences in peak blood lactate at 24 h after ECMO, liver dysfunction and multiple organ dysfunction syndrome (MODS) in the survival group (p < 0.05). Cox regression analysis showed that peak blood lactate at 24 h after ECMO (HR = 1.074, 95% CI: 1.005-1.149, p = 0.036) and MODS (HR = 4.120, 95% CI: 1.373-12.362, p = 0.012) were related risk factors affecting the prognosis of infants. The best cutoff value for the peak blood lactate at 24 h after ECMO was 10.2 mmol/L. The area under the curve (AUC) for predicting the 30-day survival rate of the ECMO assisted infants after discharge from hospital was 0.770 (95% CI: 0.592-0.948, p = 0.018), with a sensitivity of 94.1% and specificity of 54.5%. CONCLUSION: The peak blood lactate at 24 h after ECMO can predict the 30-day mortality after discharge of infants treated with ECMO after complex cardiac surgery. The best cut-off value for peak blood lactate at 24 h after ECMO was 10.2 mmol/L.

FeCoNi Ternary Nano-Alloys Embedded in a Nitrogen-Doped Porous Carbon Matrix with Enhanced Electrocatalysis for Stable Lithium-Sulfur Batteries.

The application of composite materials that combine the advantages of carbonaceous material and metal alloy proves to be a valid method for improving the performance of lithium-sulfur batteries (LSBs). Herein iron-cobalt-nickel (FeCoNi) ternary alloy nanoparticles (FNC) that spread on nitrogen-doped carbon (NC) are obtained by a strategy of low-temperature sol-gel followed by annealing at 800 °C under an argon/hydrogen atmosphere. Benefiting from the synergistic effect of different components of FNC and the conductive network provided by the NC, not only can the "shuttle effect" of lithium polysulfides (LiPS) be suppressed, but also the conversion of LiPS, the diffusion of Li+, and the deposition of Li2S can be accelerated. Taking advantage of those merits, the batteries assembled with an FNC@NC-modified polypropylene (PP) separator (FNC@NC//PP) can deliver a high reversible specific capacity of 1325 mAh g-1 at 0.2 C and maintain 950 mAh g-1 after 200 cycles, and they can also achieve a low capacity fading rate of 0.06% per cycle over 500 cycles at 1 C. More impressively, even under harsh test conditions (the ratio of electrolyte to sulfur (E/S) = 6 µL mg-1 and sulfur loading = 4.7 mg cm-2 and E/S = 10 µL mg-1 and sulfur loading = 5.9 mg cm-2), the area capacity of batteries is still much higher than 4 mAh cm-2.

Effects of Tea Polyphenol Palmitate Existing in the Oil Phase on the Stability of Myofibrillar Protein O/W Emulsion.

This study aimed to explore the effect of adding different concentrations (0, 0.01%, 0.03%, and 0.05% (w/w)) of tea polyphenol palmitate (TPP) in the oil phase on the emulsifying properties of 5 and 10 mg/mL myofibrillar protein (MP). Particle size results revealed that the flocculation of droplets increased as TPP concentration increased and that droplets in 5 mg/mL MP emulsions (25−34 µm) were larger than in 10 mg/mL MP emulsions (14−22 µm). The emulsifying activity index of 5 mg/mL MP emulsions decreased with increasing TPP concentration. The micrographs showed that the droplets of MP emulsions exhibited extensive flocculation at TPP concentrations >0.03%. Compared with 5 mg/mL MP emulsions, 10 mg/mL MP emulsions showed better physical stability and reduced flocculation degree, which coincided with lower delta backscattering intensity (ΔBS) and Turbiscan stability index values. The flow properties of emulsions can be successfully depicted by Ostwald−de Waele models (R2 > 0.99). The concentrations of TPP and protein affect the K values of emulsions (p < 0.05). Altogether, increased protein concentration in the continuous phase could improve emulsion stability by increasing viscosity, offsetting the adverse effects of TPP to a certain extent. This study is expected to promote the rational application of TPP in protein emulsion products of high quality and acceptability.

The Relationship Between the Neutrophil to Lymphocyte Ratio, The Platelet to Lymphocyte Ratio, and Cardiac Syndrome X.

Objective: This study aims to investigate the relationship between the neutrophil to lymphocyte ratio (NLR), the platelet to lymphocyte ratio (PLR), and cardiac syndrome X (CSX). Methods: A total of 102 patients with CSX who were hospitalized in the Cardiology Department of our hospital from December 2018 to December 2020 were enrolled in the CSX group, and 102 subjects who underwent physical examinations during the same period were included in the control group. An automatic blood cell analyzer was adopted to detect the neutrophil count (NC), lymphocyte count (LC), and number of platelets (PLT) in the whole blood of the subjects in both groups, and the NLR and PLR were calculated. Electrocardiography was conducted on the subjects in both groups to detect whether any abnormality existed in the ST segment. The receiver operating curve (ROC) was used to evaluate the diagnostic value of each indicator of CSX, and multivariate logistic regression analysis was adopted for the analysis of the influencing factors. Results: No significant differences existed in age, gender, smoking history, or family history of diabetes mellitus, hypertension, and tumors between the two groups (p > 0.05). When compared with the control group, the NC, PLT, NLR, PLR, and rate of abnormality of the ST segment on the electrocardiogram were significantly higher, and the LC was significantly lower in the CSX group (p < 0.05). Multivariate logistic regression analysis showed that the ST-segment abnormality (3.95 [2.10~7.41]; NLR > 2.21, 3.46 [1.87~6.39]; and PLR > 119.77, 3.66 [1.99~6.73]) was a correlated risk factor for the occurrence of CSX (p < 0.05). Conclusion: Both the NLR and PLR in patients with CSX were significantly elevated, and both have a certain predictive value for the occurrence of CSX and are expected to be effective biomarkers for CSX.

FGA inhibits metastases and induces autophagic cell death in gastric cancer via inhibiting ITGA5 to regulate the FAK/ERK pathway.

This study aims to investigate the expression levels of fibrinogen α chain (FGA) in human gastric cancer (GC) tissues and cell lines, clarify its role in gastric cancer progression, and explore its underlying mechanism. Bioinformatics analysis, Immunoblot, Immunohistochemical (IHC), and quantitative PCR assays were performed to assess the expression of FGA in human gastric cancer tissues and cell lines. CCK-8 and colony formation assays were performed to detect its role in the proliferation of gastric cancer cells. Wound healing, transwell, and Immunofluorescence were performed to detect its effects on gastric cancer cell motility and epithelial-mesenchymal transition (EMT) processes. Luciferase and CHIP assays were performed to confirm the transcriptional regulation of FGA on ITGA5. Immunoblot assays and double-label RFP-GFP-LC3 immunofluorescence analysis were conducted to detect its effects on gastric cancer cell autophagy and FAK/ERK pathway, and in vivo tumor growth assays were further performed. We found the low expression of FGA in human gastric cancer tissues and cell lines. FGA suppressed gastric cancer cell proliferation, motility, and EMT process, and stimulated cell autophagy. We further found that FGA suppressed the expression of Integrin-α5 (ITGA5) and inhibited the FAK/ERK pathway, therefore suppressing the progression of gastric cancer. The in vivo assays further confirmed that FGA suppressed tumor growth of gastric cancer cells in the BALB/c nude mice (18-22 g, female, 8-week-old) through suppressing ITGA5-mediated FAK/ERK pathway in mice. We demonstrated the mechanism underlying FGA suppressing gastric cancer progression, and therefore we thought FGA could serve as a tumor suppressor protein in gastric cancer.

Focal adhesion kinase-related non-kinase ameliorates liver fibrosis by inhibiting aerobic glycolysis via the FAK/Ras/c-myc/ENO1 pathway.

BACKGROUND: Hepatic stellate cell (HSC) hyperactivation is a central link in liver fibrosis development. HSCs perform aerobic glycolysis to provide energy for their activation. Focal adhesion kinase (FAK) promotes aerobic glycolysis in cancer cells or fibroblasts, while FAK-related non-kinase (FRNK) inhibits FAK phosphorylation and biological functions. AIM: To elucidate the effect of FRNK on liver fibrosis at the level of aerobic glycolytic metabolism in HSCs. METHODS: Mouse liver fibrosis models were established by administering CCl4, and the effect of FRNK on the degree of liver fibrosis in the model was evaluated. Transforming growth factor-ß1 was used to activate LX-2 cells. Tyrosine phosphorylation at position 397 (pY397-FAK) was detected to identify activated FAK, and the expression of the glycolysis-related proteins monocarboxylate transporter 1 (MCT-1) and enolase1 (ENO1) was assessed. Bioinformatics analysis was performed to predict putative binding sites for c-myc in the ENO1 promoter region, which were validated with chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays. RESULTS: The pY397-FAK level was increased in human fibrotic liver tissue. FRNK knockout promoted liver fibrosis in mouse models. It also increased the activation, migration, proliferation and aerobic glycolysis of primary hepatic stellate cells (pHSCs) but inhibited pHSC apoptosis. Nevertheless, opposite trends for these phenomena were observed after exogenous FRNK treatment in LX-2 cells. Mechanistically, the FAK/Ras/c-myc/ENO1 pathway promoted aerobic glycolysis, which was inhibited by exogenous FRNK. CONCLUSION: FRNK inhibits aerobic glycolysis in HSCs by inhibiting the FAK/Ras/c-myc/ENO1 pathway, thereby improving liver fibrosis. FRNK might be a potential target for liver fibrosis treatment.

HOXB13 suppresses proliferation, migration and invasion, and promotes apoptosis of gastric cancer cells through transcriptional activation of VGLL4 to inhibit the involvement of TEAD4 in the Hippo signaling pathway.

Gastric cancer (GC) is one of the most common types of malignancy worldwide and is accompanied by both high mortality and morbidity rates. Homeobox B13 (HOXB13) has been reported to act as a tumor suppressor gene in multiple types of human cancer. The present study aimed to investigate the effects and potential underlying molecular mechanisms of HOXB13 in the progression of GC. The expression of HOXB13 in GC cells was first examined using the Cancer Cell Line Encyclopedia database and subsequently validated in a number of GC cell lines. Following HOXB13 overexpression (Ov­HOXB13), HGC­27 cell proliferation was evaluated by colony formation and Cell Counting Kit­8 assays. Wound healing and Matrigel assays were used to determine the migratory and invasive abilities, respectively. Additionally, cell apoptosis was assessed using TUNEL staining, and the expression of apoptosis­related proteins was detected by western blot analysis. Subsequently, TEA domain transcription factor 4 (TEAD4) was overexpressed to evaluate the effects on HGC­27 cell proliferation, migration, invasion and apoptosis following co­transfection with Ov­HOXB13. The potential binding sites of HOXB13 on the vestigial­like family member 4 (VGLL4) promoter were verified using chromatin immunoprecipitation and dual luciferase reporter assays. Moreover, the expression levels of proteins involved in the Hippo signaling pathway were analyzed using western blotting. The results revealed that the expression of HOXB13 was notably lower in GC cells compared with normal gastric cells. The overexpression of HOXB13 significantly inhibited the proliferation, migration and invasion, but promoted the apoptosis of HGC­27 cells. Moreover, Ov­HOXB13 downregulated TEAD4 expression. Notably, Ov­TEAD4 transfection partially reversed the effects of Ov­HOXB13 on the cellular behaviors of HGC­27 cells. HOXB13 was also confirmed to bind with the VGLL4 promoter. The knockdown of VGLL4 restored the inhibitory effects of Ov­HOXB13 on the expression levels of VGLL4 and Hippo pathway signaling proteins. In conclusion, the findings of the present study suggested that Ov­HOXB13 may suppress the proliferation, migration and invasion, and promote the apoptosis of GC cells through the transcriptional activation of VGLL4 to inhibit the involvement of TEAD4 in the Hippo signaling pathway. These results may provide novel and potent targets for the treatment of GC.