Obeticholic Acid Inhibit Mitochondria Dysfunction Via Regulating ERK1/2-DRP Pathway to Exert Protective Effect on Lipopolysaccharide-Induced Myocardial Injury.

Farnesoid X receptor (FXR) plays critical regulatory roles in cardiovascular physiology/pathology. However, the role of FXR agonist obeticholic acid (OCA) in sepsis-associated myocardial injury and underlying mechanisms remain unclear. C57BL/6J mice are treated with OCA before lipopolysaccharide (LPS) administration. The histopathology of the heart and assessment of FXR expression and mitochondria function are performed. To explore the underlying mechanisms, H9c2 cells, and primary cardiomyocytes are pre-treated with OCA before LPS treatment, and extracellular signal-regulated protein kinase (ERK) inhibitor PD98059 is used. LPS-induced myocardial injury in mice is significantly improved by OCA pretreatment. Mechanistically, OCA pretreatment decreased reactive oxygen species (ROS) levels and blocked the loss of mitochondrial membrane potential (ΔΨm) in cardiomyocytes. The expression of glutathione peroxidase 1 (GPX1), superoxide dismutase 1 (SOD1), superoxide dismutase 2 (SOD2), and nuclear factor erythroid 2-related factor 2 (NRF-2) increased in the case of OCA pretreatment. In addition, OCA improved mitochondria respiratory chain with increasing Complex I expression and decreasing cytochrome C (Cyt-C) diffusion. Moreover, OCA pretreatment inhibited LPS-induced mitochondria dysfunction via suppressing ERK1/2-DRP signaling pathway. FXR agonist OCA inhibits LPS-induced mitochondria dysfunction via suppressing ERK1/2-DRP signaling pathway to protect mice against LPS-induced myocardial injury.

Nursing Care of a Child With Delirium Receiving Venoarterial Extracorporeal Membrane Oxygenation: A Case Report.

INTRODUCTION: Children receiving extracorporeal membrane oxygenation are prone to delirium. This case report describes the nursing care of a child with delirium who received venoarterial extracorporeal membrane oxygenation. Relevant interventions and precautions are also discussed. CLINICAL FINDINGS: A 6-year-old girl was admitted to the pediatric intensive care unit with a 2-day history of vomiting and fever. The child underwent cannulation for venoarterial extracorporeal membrane oxygenation. DIAGNOSIS: The child was diagnosed with acute fulminant myocarditis, cardiac shock, and ventricular arrhythmia. INTERVENTIONS: On the third day of extracorporeal membrane oxygenation, bedside nurses began using the Cornell Assessment of Pediatric Delirium to assess the child for delirium symptoms. The team of physicians and nurses incorporated a nonpharmacologic delirium management bundle into pediatric daily care. Delirium screening, analgesia and sedation management, sleep promotion, and family participation were implemented. OUTCOMES: During the 18 days of pediatric intensive care unit hospitalization, the child had 6 days of delirium: 1.5 days of hypoactive delirium, 1.5 days of hyperactive delirium, and 3 days of mixed delirium. The child was successfully discharged home on hospital day 22. CONCLUSION: Caring for a child with delirium receiving venoarterial extracorporeal membrane oxygenation required multidimensional nursing capabilities to prevent and reduce delirium while ensuring safe extracorporeal membrane oxygenation. This report may assist critical care nurses caring for children under similar circumstances.

Sequential respiratory support in septic patients undergoing continuous renal replacement therapy: A study based on MIMIC-III database.

Objective: Oxygen and hemodynamic management are important for providing a sufficient adequate oxygen-containing blood to the organs for septic patients. In present study, we aimed to explore the application of sequential respiratory support (SRS) and the association of SRS with the outcome of septic patients who needed continuous renal replacement therapy (CRRT). Methods: We extracted the medical information of septic patients who received CRRT within 24 h of intensive care unit (ICU) admission from the MIMIC-III v1.4. SRS was defined as receiving firstly oxygen therapy followed by mechanical ventilation (MV) within 24 h of admission to ICU. The propensity score matching (PSM) was performed to compare the differences in clinical characteristics and outcomes of patients with or without SRS. Finally, we developed logistic regression models to analyze the effects of SRS on hospital mortality. Results: A total of 181 patients entered in this study, and there were 80 patients undergoing MV including SRS group (n = 61) and non-SRS group (n = 19). In the multivariate logistic regression, the value of SRS was associated with the lower risk of hospital mortality adjusted by minimum systolic BP (SBP), maximum lactate, vasopressor use, and sequential organ failure assessment (SOFA) score or Logistic Organ Dysfunction System (LODS) scores within the first 24 h of ICU stay. After PSM adjusted by SBP, maximum lactate, vasopressor use, SOFA, and LODS, there were 31 patients in SRS group with a and 18 cases in non-SRS group, displaying a significantly lower hospital mortality in SRS group than that in patients without SRS (19.4 % vs. 83.3 %, P < 0.001). In addition, age, qSOFA, necessitating the administration of vasopressor, and duration of vasopressor were significantly correlated with the hospital mortality in septic patients undergoing CRRT and SRS. Conclusions: Receiving SRS within the first 24 h upon admission to the ICU was independently associated with the hospital mortality in patient with sepsis undergoing CRRT, and patients who were directly received MV had a high risk of death.

Exploring Patients' Intentions for Usage of Video Telemedicine Follow-Up Services: Cross-Sectional Study.

Background: Data suggest that regarding completion rates and lower readmission rates, video telemedicine follow-up is as efficient as in-person consultations. However, evidence of patients' intention to adopt such service is lacking. The objective of this study was to determine the essential factors influencing Chinese patients' intention to adopt video telemedicine follow-up. Methods: The researchers extended the technology acceptance model (TAM) by incorporating trust, subjective norms (SNs), perceived risk (PR), and perceived disease threat (PDT). A survey was conducted with 793 Chinese patients, and the collected data were analyzed using the partial least-squares approach. Results: The study revealed that trust emerged as the strongest factor influencing patients' behavioral intention (BI) to use video telemedicine follow-up, followed by SNs, perceived ease of use (PEOU), and perceived usefulness (PU). PR and PDT had no significant influence on patients' intention to adopt video telemedicine follow-up. PEOU mediated the relationship between trust, SNs, and BI, and PU mediated the relationship between trust and BI. The study also found that gender, age, and usage experience moderated certain relationships in the model. Conclusions: Our findings support the use of the extended TAM in understanding individual's motivations for using video telemedicine follow-up in China. In addition, this study contributes to the existing literature on telemedicine promotion by identifying significant mediation mechanisms. These findings have practical implications for planning, creating, and implementing improved video telemedicine follow-up services.

Efficient and stable acidic CO2 electrolysis to formic acid by a reservoir structure design.

Electrochemical synthesis of valuable chemicals and feedstocks through carbon dioxide (CO2) reduction in acidic electrolytes can surmount the considerable CO2 loss in alkaline and neutral conditions. However, achieving high productivity, while operating steadily in acidic electrolytes, remains a big challenge owing to the severe competing hydrogen evolution reaction. Here, we show that vertically grown bismuth nanosheets on a gas-diffusion layer can create numerous cavities as electrolyte reservoirs, which confine in situ-generated hydroxide and potassium ions and limit inward proton diffusion, producing locally alkaline environments. Based on this design, we achieve formic acid Faradaic efficiency of 96.3% and partial current density of 471 mA cm-2 at pH 2. When operated in a slim continuous-flow electrolyzer, the system exhibits a full-cell formic acid energy efficiency of 40% and a single pass carbon efficiency of 79% and performs steadily over 50 h. We further demonstrate the production of pure formic acid aqueous solution with a concentration of 4.2 weight %.

Gerhardtite as a Precursor to an Efficient CO-to-Acetate Electroreduction Catalyst.

Carbon-carbon coupling electrochemistry on a conventional copper (Cu) catalyst still undergoes low selectivity among many different multicarbon (C2+) chemicals, posing a grand challenge to achieve a single C2+ product. Here, we demonstrate a laser irradiation synthesis of a gerhardtite mineral, Cu2(OH)3NO3, as a catalyst precursor to make a Cu catalyst with abundant stacking faults under reducing conditions. Such structural perturbation modulates electronic microenvironments of Cu, leading to improved d-electron back-donation to the antibonding orbital of *CO intermediates and thus strengthening *CO adsorption. With increased *CO coverage on the defect-rich Cu, we report an acetate selectivity of 56 ± 2% (compared to 31 ± 1% for conventional Cu) and a partial current density of 222 ± 7 mA per square centimeter in CO electroreduction. When run at 400 mA per square centimeter for 40 h in a flow reactor, this catalyst produces 68.3 mmol of acetate throughout. This work highlights the value of a Cu-containing mineral phase in accessing suitable structures for improved selectivity to a single desired C2+ product.

Synthesis of an aggregation-induced emission-based fluorescent probe based on rupestonic acid.

Chinese herbal medicine and Chinese patent medicine have been widely applied for cancer care in China. Rupestonic acid, an active ingredient of Artemisia rupestris L., has recently been confirmed to have certain anti-tumor effects in vitro. In this study, we employed the application of a commonly devoted triphenylamine as a fluorophore and the addition of 2,4-thiazolidinedione as a bridge to integrate rupestonic acid into the AIE system to create an fluorescent probe with anti-tumor properties. The spectral, cytotoxic, and cellular imaging properties of the probe were measured. Its promising responses make possible the application of the probe in antitumor theragnostic systems.

ATF4 knockdown in macrophage impairs glycolysis and mediates immune tolerance by targeting HK2 and HIF-1α ubiquitination in sepsis.

Strengthened glycolysis is crucial for the macrophage pro-inflammatory response during sepsis. Activating transcription factor 4 (ATF4) plays an important role in regulating glucose and lipid metabolic homeostasis in hepatocytes and adipocytes. However, its immunometabolic role in macrophage during sepsis remains largely unknown. In the present study, we found that the expression of ATF4 in peripheral blood mononuclear cells (PBMCs) was increased and associated with glucose metabolism in septic patients. Atf4 knockdown specifically decreased LPS-induced spleen macrophages and serum pro-inflammatory cytokines levels in mice. Moreover, Atf4 knockdown partially blocked LPS-induced pro-inflammatory cytokines, lactate accumulation and glycolytic capacity in RAW264.7. Mechanically, ATF4 binds to the promoter region of hexokinase II (HK2), and interacts with hypoxia inducible factor-1α (HIF-1α) and stabilizes HIF-1α through ubiquitination modification in response to LPS. Furthermore, ATF4-HIF-1α-HK2-glycolysis axis launches pro-inflammatory response in macrophage depending on the activation of mammalian target of rapamycin (mTOR). Importantly, Atf4 overexpression improves the decreased level of pro-inflammatory cytokines and lactate secretion and HK2 expression in LPS-induced tolerant macrophages. In conclusion, we propose a novel function of ATF4 as a crucial glycolytic activator contributing to pro-inflammatory response and improving immune tolerant in macrophage involved in sepsis. So, ATF4 could be a potential new target for immunotherapy of sepsis.

Tumor Eradication by Boron Neutron Capture Therapy with 10 B-enriched Hexagonal Boron Nitride Nanoparticles Grafted with Poly(Glycerol).

Boron neutron capture therapy (BNCT) has emerged as a treatment modality with high precision and efficacy of intractable tumors. At the core of effective tumor BNCT are 10 B carriers with facile preparation as well as advantageous pharmacokinetic and therapeutic profiles. Herein, the design and preparation of sub-10 nm 10 B-enriched hexagonal boron nitride nanoparticles grafted with poly(glycerol) (h-10 BN-PG), and their application to cancer treatment by BNCT are reported. By virtue of their small particle size and outstanding stealth property, h-10 BN-PG nanoparticles accumulate efficiently in murine CT26 colon tumors with a high intratumor 10 B concentration of 8.8%ID g-1 or 102.1 µg g-1 at 12 h post-injection. Moreover, h-10 BN-PG nanoparticles penetrate into the inside of the tumor parenchyma and then are taken up by the tumor cells. BNCT comprising a single bolus injection of h-10 BN-PG nanoparticles and subsequent one-time neutron irradiation results in significant shrinkage of subcutaneous CT26 tumors. h-10 BN-PG-mediated BNCT not only causes direct DNA damage to the tumor cells, but also triggers pronounced inflammatory immune response in the tumor tissues, which contributes to long-lasting tumor suppression after the neutron irradiation. Thus, the h-10 BN-PG nanoparticles are promising BNCT agents to eradicate tumor through highly efficient 10 B accumulation.

Risk factors of delirium in a paediatric intensive care unit: A prospective case series study.

BACKGROUND: Delirium is one of the most common complications in critically ill children. Once delirium occurs, it will cause physical and psychological distress in children and increase the length of their ICU stay and hospitalization costs. Understanding the risk factors for delirium in critically ill children can help develop targeted nursing interventions to reduce the incidence of delirium. AIMS: To investigate the incidence and the risk factors of delirium in the paediatric intensive care unit (PICU). STUDY DESIGN: We performed a prospective observational study in critically ill patients in the PICU between February and July 2020. Delirium was diagnosed by the Cornell Assessment of Paediatric Delirium (CAPD) and the Richmond Agitation Sedation Scale and analysed via univariate analysis and multivariate logistic regression to determine the independent risk factors of delirium in critically ill children. RESULTS: The study enrolled 315 patients ranging in age from 1-202 (65.3-54.3) months, with 56.2% (n = 177) being male. The incidence of delirium was 29.2% (n = 92) according to CAPD criteria. Among them, 33 cases (35.9%) were of hyperactive delirium, 16 cases (17.4%) were of hypoactive delirium, and 43 cases (46.7%) were of mixed delirium. By using stepwise logistic regression, the independent risk factors of delirium included mechanical ventilation (odds ratio [OR], 11.470; 95% confidence interval [CI], 4.283-30.721), nervous system disease (OR, 5.596; 95%CI, 2.445 to 12.809), developmental delay (OR, 5.157; 95% CI, 1.990-13.363), benzodiazepine (OR, 3.359; 95% CI 1.278-8.832), number of catheters (OR, 1.918; 95% CI, 1.425 to 2.582), and age (OR, 0.985; 95% confidence interval CI, 0.976-0.993). CONCLUSIONS: Delirium is a common complication in the PICU. The independent risk factors include mechanical ventilation, nervous system disease, developmental delay, benzodiazepines, higher number of catheters, and younger age. This study may help develop intervention strategies to reduce the incidence of delirium in critically ill children by targeting modifiable risk factors. RELEVANCE TO CLINICAL PRACTICE: Recommendations for practice include paying attention to high-risk children in the ICU who are prone to delirium, removing influencing factors as soon as possible, and providing targeted nursing interventions.

Combination of Plasma Exchange and Adsorption Versus Plasma Exchange in Pediatric Acute Liver Failure: A Multicenter Cohort Study.

OBJECTIVES: This study aimed to compare the efficacy of double plasma molecular adsorption system (DPMAS) with half-dose plasma exchange (PE) to that of full-dose PE in pediatric acute liver failure (PALF). METHODS: This multicenter, retrospective cohort study was conducted in 13 pediatric intensive care units in Shandong Province, China. DPMAS+PE and single PE therapies were performed in 28 and 50 cases, respectively. The patients' clinical information and biochemical data were obtained from the patients' medical records. RESULTS: The severity of illness did not differ between the 2 groups. At 72 hours after treatment, comparing with PE group, the rates of decline of Pediatric model for End-stage Liver Disease and Pediatric Sequential Organ Failure Assessment scores as well as total bilirubin blood ammonia and interleukin-6 were significantly higher, while the short-term effective rate (75.0% vs 44.0%, P = 0.008) was significantly higher in the DPMAS+PE group. The volume of plasma consumption (26.5 vs 51.0 mL/kg, P = 0.000) and the rate of adverse events (3.6% vs 24.0%, P = 0.026) were lower in the DPMAS+PE group than in the PE group, respectively. However, there was no statistical difference in the 28-day mortality between the 2 groups (21.4% vs 40.0%, P > 0.05). CONCLUSIONS: For PALF patients, both DPMAS + half-dose PE and full-dose PE could improve the liver function, while DPMAS + half-dose PE could significantly reduce plasma consumption without obvious adverse effects in contrast with full-dose PE. Thus, DPMAS + half-dose PE may be a suitable alternative method for PALF in the context of the increasingly tight blood supply situation.

A New Species of the Genus Achalinus (Squamata: Xenodermidae) from the Dabie Mountains, Anhui, China.

A new species of Xenodermid snake, Achalinus dabieshanensissp. nov., was described based on three specimens (two female and one male) collected from the Dabie Mountains of western Anhui Province. It can be distinguished from known congeners by a significant genetic divergence in the mitochondrial gene fragment COI (p-distance ≥ 9.4%) and the following combination of characteristics: (1) length of the suture between the internasals being distinctly shorter than between the prefrontals; (2) a single loreal; (3) dorsal scales strongly keeled, in 23 rows throughout the body; (4) two pairs of prefrontals; (5) six supralabials; (6) five infralabials; (7) temporals 2 + 2 + 3 (or 2 + 2 + 4); (8) 141-155 ventrals; (9) 45-55 subcaudals, unpaired; (10) anal entire; (11) weakly iridescent tinged, uniform, brown to black dorsum with vertebral scales and about three adjacent dorsal scales dark brown forming a longitudinal vertebral line from posterior margin of parietals to tail tip; (12) light brown venter, ventral shields wide, visible on both sides, light brown flanks, giving the appearance of a black subcaudal streak. The recognition of the new species increases the number of described Achalinus species to 22.

Fabrication and Computational Study of a Chemiresistive NO2 Gas Sensor Based on the Carbon Dots-WO3 Heterostructure for Operating below Room Temperature.

For a long time, chemiresistive gas sensors based on metal oxide semiconductors (MOSs) suffer from higher operating temperatures, resulting in higher energy consumption and instability of the sensors. Generally, a MOS-based chemiresistive gas sensor being able to work at room temperature is considered to be outstanding already. Here, a highly sensitive NO2 gas sensor based on the carbon dots-WO3 heterostructure, which can work below room temperature at -6 °C, is fabricated. At 18, -1, and -6 °C, its detection limits are 200 ppb, 5 ppm, and 20 ppm, respectively, and the corresponding response values (Ra/Rg) are 1.11, 1.04, and 1.13, respectively. The sensor exhibits good selectivity, stability, and linearity between relative humidity and response values too. A peculiar response behavior was observed. Toward oxidizing gas NO2, the resistance of the sensor based mainly on n-type WO3 shows decrease behavior. Its peculiar response behavior and strong gas sensing ability at lower temperatures were elucidated theoretically using the results of first-principles calculations. The reduction of NO2 into NO by surface oxygen vacancies of WO3 and the following adsorption of NO on the surface of WO3 lead to electron transfer from NO to WO3, and the Fermi level shifts toward the conduction band, making the sensor exhibit the peculiar response behavior. The stronger adsorption capability of carbon dots toward NO2 and a synergistic effect of carbon dots and WO3 together make the sensor capable of working at lower temperatures and own higher sensitivity.

The novel biomarkers for assessing clinical benefits of continuous renal replacement therapy in pediatric sepsis: a pilot study.

BACKGROUND: Continuous renal replacement therapy (CRRT) has been considered as an adjuvant therapy for sepsis. However, the novel biomarker to evaluate the benefits of CRRT is limited. The aim of this study was to explore the novel biomarkers involved in the impact of CRRT in pediatric sepsis. METHODS: The serum proteomic profiles on the 7th day after CRRT (CRRT 7th day) compared with before CRRT (CRRT 1st day) was determined in 3 children with sepsis as a discovery set. The screened candidates were confirmed in the validation cohort including patients received CRRT (CRRT group) and without CRRT (non-CRRT group). We defined that pediatric sequential organ failure assessment score (pSOFA) in pediatric patients with sepsis decreased by 2 points or more on the CRRT 1st day compared with CRRT initiation as CRRT responders. The changes of serum biomarkers were compared between CRRT responders and CRRT non-responders. Moreover, correlation analysis was further conducted in pediatric sepsis. RESULTS: A total of 145 differentially expressed proteins were found according to the serum proteomics profiles. By visualizing the interaction between the differential proteins, 6 candidates (Lysozyme C [LYZ], Leucine-rich alpha-2-glycoprotein [LRG1], Fibromodulin [FMOD], Alpha-1-antichymotrypsin [SERPINA3], L-selectin [SELL], Monocyte differentiation antigen CD14 [CD14]) were screened. In the validation cohort, serum levels of LYZ and LRG1 showed a higher trend on the CRRT 7th day than that on the 1st day in the non-CRRT group. However, the changes in levels of LYZ and LRG1 on the 7th day was significant in the CRRT group (p = 0.016, p = 0.009, respectively). Moreover, the levels of LYZ and LRG1 on the CRRT 7th day in the CRRT group were significantly higher than that in the non-CRRT group (p < 0.001, p = 0.025). Decreased levels of CD14 were associated with sepsis recovery, but not associated with CRRT. There were no significantly difference in serum FMOD, SERPINA3, and SELL levels. Importantly, serum LYZ and LRG1 levels changed in CRRT responders, but not CRRT non-responders. Further analysis indicated that serum LYZ levels were correlated to total platelet counts, aspartate aminotransferase (ALT), alanine aminotransferase (AST), and albumin levels, and serum LRG1 level were correlated to total platelet count and TBIL levels on the 1st day in the CRRT group. Protein-protein interaction network analysis displayed that serum LYZ and LRG1 were involved in the process of inflammatory response, leucocytes adhesion to vascular endothelial cell, as well as complement activation. CONCLUSION: Elevated serum LYZ and LRG1 levels are associated with clinical benefits of CRRT during sepsis.

RAGE inhibition alleviates lipopolysaccharides-induced lung injury via directly suppressing autophagic apoptosis of type II alveolar epithelial cells.

BACKGROUND: Advanced glycation end product receptor (RAGE) acts as a receptor of pro-inflammatory ligands and is highly expressed in alveolar epithelial cells (AECs). Autophagy in AECs has received much attention recently. However, the roles of autophagy and RAGE in the pathogenesis of acute lung injury remain unclear. Therefore, this study aimed to explore whether RAGE activation signals take part in the dysfunction of alveolar epithelial barrier through autophagic death. METHODS: Acute lung injury animal models were established using C57BL/6 and Ager gene knockout (Ager -/- mice) mice in this study. A549 cells and primary type II alveolar epithelial (ATII) cells were treated with siRNA to reduce Ager gene expression. Autophagy was inhibited by 3-methyladenine (3-MA). Lung injury was assessed by histopathological examination. Cell viability was estimated by cell counting kit-8 (CCK-8) assay. The serum and bronchoalveolar lavage fluid (BALF) levels of interleukin (IL)-6, IL-8 and soluble RAGE (sRAGE) were evaluated by Enzyme-linked immunosorbent assay (ELISA). The involvement of RAGE signals, autophagy and apoptosis was assessed using western blots, immunohistochemistry, immunofluorescence, transmission electron microscopy and TUNEL test. RESULTS: The expression of RAGE was promoted by lipopolysaccharide (LPS), which was associated with activation of autophagy both in mice lung tissues and A549 cells as well as primary ATII cells. sRAGE in BALF was positively correlated with IL-6 and IL-8 levels. Compared with the wild-type mice, inflammation and apoptosis in lung tissues were alleviated in Ager-/- mice. Persistently activated autophagy contributed to cell apoptosis, whereas the inhibition of autophagy by 3-MA protected lungs from damage. In addition, Ager knockdown inhibited LPS-induced autophagy activation and attenuated lung injury. In vitro, knockdown of RAGE significantly suppressed the activation of LPS-induced autophagy and apoptosis of A549 and primary ATII cells. Furthermore, RAGE activated the downstream STAT3 signaling pathway. CONCLUSION: RAGE plays an essential role in the pathogenesis of ATII cells injury. Our results suggested that RAGE inhibition alleviated LPS-induced lung injury by directly suppressing autophagic apoptosis of alveolar epithelial cells.

Cyanidin inhibits glioma stem cells proliferation through the Wnt signaling pathway.

BACKGROUND: Cyanidin has a protective effect on the nervous system and has been reported to treat tumor effectively. However, its impact on glioma stem cells (GSC) is unknown. METHODS: Using seven GSC lines, the anti-tumor effect of cyanidin is tested. The effect of cyanidin on the cell viability in each cell line is evaluated. Wnt signaling pathway-related genes are checked after treatment of cyanidin. Cytoplasmic/nuclear ß-catenin protein levels post cyanidin treatment is detected. Protein levels of c-Myc after cyanidin treatment are determined. Twist1 and Snail1 protein levels after cyanidin treatment are checked as well. RESULTS: Cyanidin significantly reduces the cell viability of all GSCs, and exhibited the most substantial effect in GBM2 but no apparent effect in 293T cells. It can regulate the Wnt signaling pathway of all GSC lines. In the GBM2, GBM7, G166, and G179 cell lines, there is upregulation of WNT1 and MYC genes, while in the G144 and GliNS2 cell line, these two genes are down-regulated after cyanidin treatment. Cytoplasmic and nuclear protein levels of ß-catenin in all cell lines are down-regulated. Cyanidin treatment significantly decreases the protein level for c-Myc in the GBM2 cell line compared with untreated cells, not in G144 or GliNS2 cells. Furthermore, cyanidin strongly reduces the expression of Twist1 and Snail1 in GBM2, G179, and G144 cell lines, while the GliNS2 cells show an opposite change in the cytoplasm and no change in nuclear. CONCLUSION: Cyanidin exerts an anti-tumor effect in glioma stem cell lines, probably through the Wnt signaling pathway.

Activating transcription factor 4 protects mice against sepsis-induced intestinal injury by regulating gut-resident macrophages differentiation.

BACKGROUND: Gut-resident macrophages (gMacs) supplemented by monocytes-to-gMacs differentiation play a critical role in maintaining intestinal homeostasis. Activating transcription factor 4 (ATF4) is involved in immune cell differentiation. We therefore set out to investigate the role of ATF4-regulated monocytes-to-gMacs differentiation in sepsis-induced intestinal injury. METHODS: Sepsis was induced in C57BL/6 wild type (WT) mice and Atf4- knockdown ( Atf4+/ - ) mice by cecal ligation and puncture or administration of lipopolysaccharide (LPS). Colon, peripheral blood mononuclear cells, sera, lung, liver, and mesenteric lymph nodes were collected for flow cytometry, hematoxylin and eosin staining, immunohistochemistry, quantitative reverse transcription polymerase chain reaction, and enzyme-linked immunosorbent assay, respectively. RESULTS: CD64, CD11b, Ly6C, major histocompatibility complex-II (MHC-II), CX3CR1, Ly6G, and SSC were identified as optimal primary markers for detecting the process of monocytes-to-gMacs differentiation in the colon of WT mice. Monocytes-to-gMacs differentiation was impaired in the colon during sepsis and was associated with decreased expression of ATF4 in P1 (Ly6C hi monocytes), the precursor cells of gMacs. Atf4 knockdown exacerbated the impairment of monocytes-to-gMacs differentiation in response to LPS, resulting in a significant reduction of gMacs in the colon. Furthermore, compared with WT mice, Atf4+/- mice exhibited higher pathology scores, increased expression of inflammatory factor genes ( TNF-α, IL-1ß ), suppressed expression of CD31 and vascular endothelial-cadherin in the colon, and increased translocation of intestinal bacteria to lymph nodes and lungs following exposure to LPS. However, the aggravation of sepsis-induced intestinal injury resulting from Atf4 knockdown was not caused by the enhanced inflammatory effect of Ly6C hi monocytes and gMacs. CONCLUSION: ATF4, as a novel regulator of monocytes-to-gMacs differentiation, plays a critical role in protecting mice against sepsis-induced intestinal injury, suggesting that ATF4 might be a potential therapeutic target for sepsis treatment.

Willingness to engage in post-discharge follow-up service conducted via video telemedicine: Cross-sectional study.

BACKGROUND: Leading influencing factors for telemedicine implementation remain unclear, affecting the focus of intervention strategies. Despite recent effectiveness evidence of video telemedicine visits, limited evidence exists regarding patients' willingness to use video follow-up. Moreover, patients' acceptance is crucial for implementing such services. OBJECTIVE: We conducted a large-sample survey to analyze patient willingness and perceptions of post-discharge video follow-up and assessed the factors influencing their willingness during the COVID-19 outbreak. METHOD: In February and March 2022, we conducted a face-to-face questionnaire survey involving inpatients in a tertiary care hospital in Longhua District, Shenzhen, China. We assessed demographics, health-related determinants, access to technology and literacy, preferences, willingness, and opinions toward video telemedicine follow-up. We implemented random forest and logistic regression analyses to obtain reliable results. RESULTS: In total, 1,017 inpatients completed the survey. Overall, as an initial choice, 44.9 % preferred telephone consultation for post-discharge follow-up, which was followed by video telemedicine (17.1 %), WeChat voice calls (11.6 %), SMS text messages (10.7 %), WeChat graphic messages (10.5 %), and in-person visits (4.5 %). Moreover, 54.9 % were willing to experience video visits. The results highlight the perceived benefits outweighing the risks (OR 2.64, 95 % CI 1.76, 3.95), patients' trust in the physician (OR 2.41, 95 % CI 1.45, 3.99), access to a private space (OR 2.18, 95 % CI 1.01, 2.96), medium geographical distance (compared to long distance, OR 0.72, 95 % CI 0.54, 0.98), moderate disease (compared to mild disease, OR 0.75, 95 % CI 0.57, 0.99), followed by the comfort with video technology (OR 1.73, 95 % CI 1.76, 3.95), broadband internet accessibility (OR 1.56, 95 % CI 1.07, 2.27), privacy concerns (OR 0.62, 95 % CI 0.43, 0.89), and prior telemedicine video experience (OR 1.77, 95 % CI 1.15, 2.72), as factors influencing the willingness to use video follow-up. CONCLUSIONS: A low percentage of patients chose video visits as their initial decisions; nevertheless, most had a positive attitude toward video follow-up visits. The willingness to choose video telemedicine post-discharge follow-up was influenced by geographical distance, disease severity, basic telemedicine requirements, physician-patient relationship, and perceptions of video communication.

Targeted photodynamic therapy of glioblastoma mediated by platelets with photo-controlled release property.

Photodynamic therapy (PDT) has recently emerged as a promising, targeted treatment modality for glioblastoma (GBM) which is the most vicious type of brain tumor. Successful GBM-PDT hinges upon light activation of a photosensitizer accumulated in the tumor. However, inadequate tumor accumulation of photosensitizer severely limits the success of PDT of GBM. To tackle this difficulty, we herein propose a drug delivery strategy of "platelets with photo-controlled release property". This strategy exploits platelets as carriers to deliver a photosensitizer which, in the current study, is a nano-composite (BNPD-Ce6) comprised of chlorine e6 (Ce6) loaded to boron nitride nanoparticles with a surface coating of polyglycerol and doxorubicin. To demonstrate the working mechanism and therapeutic advantage of this strategy, we loaded mouse platelets with BNPD-Ce6 to yield the nano-device BNPD-Ce6@Plt. In vitro experiments showed BNPD-Ce6@Plt to have a high loading capacity and efficiency. Laser irradiation (LI) at a wavelength of 808 nm induced ROS generation in BNPD-Ce6@Plt which displayed rapid activation, aggregation, and speedy discharge of BNPD-Ce6 into co-cultured GL261 mouse GBM cells which in turn, after LI, exhibited marked ROS generation, DNA damage, reduced viability, and cell death. In vivo animal experiments, mice that were intravenously injected with BNPD-Ce6@Plt exhibited rapid and extensive BNPD-Ce6 accumulation in both subcutaneous and intra-brain GL261 tumors shortly after LI of the tumors and the tumors displayed massive tissue necrosis after LI for a second time. Finally, a PDT regimen of two intravenous BNPD-Ce6@Plt injections each followed by multiple times of extracranial LI at the tumor site significantly inhibited the growth of intra-brain GL261 tumors and markedly increased the survival of the host animals. No apparent tissue damage was found in vital organs. Our findings make a compelling case for the notion that platelets are efficient carriers that can photo-controllably deliver nano-photosensitizers to achieve highly targeted and efficacious PDT of GBM. This work presents a novel approach to GBM-PDT with great translational potential.

Continuous renal replacement therapy attenuates polymorphonuclear myeloid-derived suppressor cell expansion in pediatric severe sepsis.

Background: Myeloid-derived suppressor cells (MDSCs) expansion is an important mechanism underlying immunosuppression during sepsis. Though continuous renal replacement therapy (CRRT) may attenuate hyperinflammatory response in sepsis, its role in regulating MDSCs is unknown. The aim of this study was to assess the potential role of CRRT involved in sepsis-induced MDSCs expansion in pediatric sepsis. Method: The proportion of polymorphonuclear MDSCs (PMN-MDSCs) was detected before CRRT (pre-CRRT), at 24 hours after CRRT (CRRT 1st day) and on the 7th day after CRRT (CRRT 7th day). The correlation analyses were performed to elucidate the relationship of MDSCs with clinical indexes in sepsis. Results: Totally 22 pediatric patients with sepsis were enrolled [median age 44 (IQR15, 83) months]. PMN-MDSCs were expanded in pediatric sepsis compared with healthy controls (4.30% vs. 0.37%, P=0.04). The proportion of PMN-MDSCs showed a decreased tendency on the CRRT 7th day compared with that on the CRRT 1st day in survivors (2.29% vs.5.32%, P = 0.088). There was no significant difference in the proportion of PMN-MDSCs between survivors and non-survivors before CRRT (4.51% vs. 3.33%, P=0.745). The levels of interleukin 6 (IL-6) was decreased on the CRRT 7th day compared with CRRT 1st day in survivors. In the subgroups of patients with significantly decreased IL-6 levels after CRRT, the proportion of PMN-MDSCs on the CRRT 7th day were also significantly decreased compared with that on the CRRT 1st day (2.21% vs. 6.67%, P = 0.033). Conclusion: The proportion of PMN-MDSCs was down-regulated on the CRRT 7th day in survivors with sepsis. The reduced PMN-MDSCs expansion may relate to decreased IL-6 level.