Research Progress on Graphite-Derived Materials for Electrocatalysis in Energy Conversion and Storage.

High-performance electrocatalysts are critical to support emerging electrochemical energy storage and conversion technologies. Graphite-derived materials, including fullerenes, carbon nanotubes, and graphene, have been recognized as promising electrocatalysts and electrocatalyst supports for the oxygen reduction reaction (ORR), oxygen evolution reaction (OER), hydrogen evolution reaction (HER), and carbon dioxide reduction reaction (CO2RR). Effective modification/functionalization of graphite-derived materials can promote higher electrocatalytic activity, stability, and durability. In this review, the mechanisms and evaluation parameters for the above-outlined electrochemical reactions are introduced first. Then, we emphasize the preparation methods for graphite-derived materials and modification strategies. We further highlight the importance of the structural changes of modified graphite-derived materials on electrocatalytic activity and stability. Finally, future directions and perspectives towards new and better graphite-derived materials are presented.

Silencing of FOREVER YOUNG FLOWER-Like Genes from Phalaenopsis Orchids Promotes Flower Senescence and Abscission.

Ectopic expression of FOREVER YOUNG FLOWER (FYF) delays floral senescence and abscission in transgenic Arabidopsis. To analyze the FYF function in Phalaenopsis orchids, two FYF-like genes (PaFYF1/2) were identified. PaFYF1/2 were highly expressed in young Phalaenopsis flowers, and their expression decreased significantly afterward until flower senescence. This pattern was strongly correlated with the process of flower senescence and revealed that PaFYF1/2 function to suppress senescence/abscission during early flower development. Interestingly, in flowers, PaFYF1 was consistently expressed less in petals than in lips/sepals, whereas PaFYF2 was expressed relatively evenly in all flower organs. This difference suggests a regulatory modification of the functions of PaFYF1 and PaFYF2 during Phalaenopsis flower evolution. Delayed flower senescence and abscission, which were unaffected by ethylene treatment, were observed in 35S::PaFYF1/2 and 35S::PaFYF1/2 + SRDX transgenic Arabidopsis plants due to the downregulation of the ethylene signaling and abscission-associated genes EDF1-4, IDA and BOP1/2. These results suggest a possible repressor role for Phalaenopsis PaFYF1/2 in controlling floral senescence/abscission by suppressing ethylene signaling and abscission-associated genes. To further validate the function of PaFYF1/2, PaFYF1/2-VIGS (virus-induced gene silencing) Phalaenopsis were generated and analyzed. Promotion of senescence and abscission was observed in PaFYF1/2-VIGS Phalaenopsis flowers by the upregulation of PeEDF1/2, PeSAG39 and PeBOP1/2 expression, the early occurrence of greening according to their increased chlorophyll content and the reduction in water content in flower organs. Our results support that PaFYF1/2 function as transcriptional repressors to prohibit flower senescence and abscission in Phalaenopsis.

Selection and validation of appropriate reference genes for gene expression studies in Forsythia.

The qRT-PCR method has been widely used to detect gene expression level in plants, helping to understand the molecular mechanisms. However, there are few researches which focus on the selection of the internal reference genes in Forsythia. To select the appropriate reference genes of Forsythia aimed at qRT-PCR normalization, twelve candidate reference genes were selected from our transcriptome data. Their expression was assessed by RT-PCR analysis in 47 Forsythia samples, including 12 species cultivars, different organs and tissues. GeNorm, NormFinder, and BestKeeper software were used to select the appropriate reference genes, AG and PSY were used to verify the accuracy of the outcome. The results showed that UKN1 was a stable reference gene in leaves of twelve Forsythia germplasms and in different developmental stages of fruits. MTP, ABCT + MTP, and ABCT + MTP + TIP were stable reference genes in different organs. ACT and SDH were stable reference genes in different flower tissues and different developmental stages of the flower buds. When Forsythia plants were stressed with PEG or ABA, SDH + UKN1 + G6PD was the stable reference gene group for qRT-PCR. The results provided the basis for investigating the physiological and biochemical processes of Forsythia related to medicinal and ornamental properties, and drought-resistance in the level of gene expression.

Exploring the tissue tropism of pseudorabies virus based on miRNA level analysis.

BACKGROUND: Pseudorabies virus (PRV, or suid herpesvirus, SuHV-1), a member of the herpesvirus family, has an extremely broad host range and threatens the pig industry in China. PRV can evade host innate immunity and infect the kidney, lung, brain and other tissues. At the same time, many studies have reported that microRNA (miRNA) can affect the replication of viruses by regulating gene expression levels. RESULTS: Here, to identify changes in miRNA expression and post-transcriptional regulation associated with PRV infection in the lung, spleen, and olfactory bulb, we sequenced small RNAs in tissues of rats infected or uninfected with PRV strain XJ (PRV-XJ). Sixty-one, 199 and 29 differentially-expressed miRNAs were identified in the lung, spleen, and olfactory bulb, respectively, of infected compared with uninfected rats. Among the miRNAs differentially-expressed in PRV-infected rats, 36, 171, and 15 miRNAs showed tissue-selective expression in the olfactory bulb, lung and spleen, respectively. All differentially-expressed miRNAs were analyzed for their GO functional annotations and KEGG pathway associations . CONCLUSIONS: In PRV-XJ-infected rats, miRNAs were differentially expressed in the lung, spleen and olfactory bulb. These miRNAs were involved in regulating various pathways of the nervous, respiratory and immune systems, and may affect the tissue tropism of the virus and play pivotal roles in viral infection and proliferation.

A simple bioscore improves diagnostic accuracy of sepsis after surgery.

BACKGROUND: Rapid and accurate prediction for sepsis remains a challenge in surgical intensive care units. Detection of individual biomarkers is often of marginal usefulness, and several biomarkers are difficult to measure in the clinical setting. The aim of this study was to evaluate the diagnostic and prognostic performance of three routine biomarkers, procalcitonin (PCT), B-type natriuretic peptide (BNP), and lymphocyte percentage, as individual or in combination for sepsis in surgical critically ill patients. MATERIALS AND METHODS: Circulating PCT, BNP, and lymphocyte percentage were measured in surgical patients on admission to the intensive care unit. A bioscore system combining these biomarkers was constructed. All studied variables were analyzed according to the diagnosis and clinical outcomes of sepsis. RESULTS: A total of 320 consecutive patients were included in the analysis. One hundred fifty-six patients presented with sepsis. In the patients with sepsis, levels of PCT and BNP increased and lymphocyte percentage decreased. For individual biomarkers, PCT achieved the best area under the curve for the diagnosis of sepsis, whereas the diagnostic performance of the bioscore was better than that of each individual biomarker (area under the curve, 0.914 [95% confidence interval, 0.862-0.951]). Levels of BNP and bioscore increased in nonsurvivors in the entire cohort, but the accuracy of these two variables for mortality prediction was lower than that shown by Acute Physiology and Chronic Health Evaluation II score. Furthermore, bioscore failed to predict outcomes in septic patients. CONCLUSIONS: A simple bioscore combining PCT together with BNP and lymphocyte percentage improves the diagnostic accuracy for sepsis in surgical critically ill patients but fails to predict outcomes in surgical patients with sepsis.

[Clinical value of lung ultrasound in the late goal-directed fluid removal in critically ill patients underwent fluid resuscitation].

OBJECTIVE: To investigate the clinical value of lung ultrasound in the late goal -directed fluid removal in critically ill patients underwent fluid resuscitation. METHODS: A prospective study was conducted. Forty patients underwent fluid resuscitation were enrolled in the Department of Surgical Intensive Care Unit of The First Affiliated Hospital of Sun Yat-sen University from Jan 2015 to June 2015. Lung and heart ultrasound were conducted for lung B-lines and left ventricular ejection fraction (EF). Serum amino-terminal pro-brain natriuretic peptide (NT-proBNP), central venous pressure (CVP) and serum creatinine were also measured and fluid balance was recorded in all patients enrolled. RESULTS: Among the 40 patients enrolled, 35 patients survived and 5 died. In patients survived, B-lines reached its peak at 12(30)h after admitted to ICU. It started to decrease instantly after the peak and reached zero at (39±34) h. A higher peak was followed with more fluids to be removed later and longer ICU stay (P<0.01). Moreover, when compared with the survivors, B-lines in death reached a higher peak[7(8) vs 3(4), P<0.01]and without the tendency to drop down. EF was lower in death than in survivor (44.5%±3.5% vs 69.2%±11.0%, P<0.05). A lower EF was found to be followed with a higher peak of B-lines. The peak time of NT-proBNP and clinical dehydration treatment were later than the peak time of B-lines in survivors. CONCLUSIONS: Fluid overloading occurs in late stage after resuscitation in critically ill patients. Lung ultrasound B-lines, which is more sensitive than the NT-proBNP and CVP, could help to monitor the patient's fluid status and guide the late goal-directed fluid removal.

Palygorskite-Derived Ternary Fluoride with 2D Ion Transport Channels for Ampere Hour-Scale Li-S Pouch Cell with High Energy Density.

Although various excellent electrocatalysts/adsorbents have made notable progress as sulfur cathode hosts on the lithium-sulfur (Li-S) coin-cell level, high energy density (WG ) of the practical Li-S pouch cells is still limited by inefficient Li-ion transport in the thick sulfur cathode under low electrolyte/sulfur (E/S) and negative/positive (N/P) ratios, which aggravates the shuttle effect and sluggish redox kinetics. Here a new ternary fluoride MgAlF5 ·2H2 O with ultrafast ion conduction-strong polysulfides capture integration is developed. MgAlF5 ·2H2 O has an inverse Weberite-type crystal framework, in which the corner-sharing [AlF6 ]-[MgF4 (H2 O)2 ] octahedra units extend to form two-dimensional Li-ion transport channels along the [100] and [010] directions, respectively. Applied as the cathode sulfur host, the MgAlF5 ·2H2 O lithiated by LiTFSI (lithium salt in Li-S electrolyte) acts as a fast ionic conductor to ensure efficient Li-ion transport to accelerate the redox kinetics under high S loadings and low E/S and N/P. Meanwhile, the strong polar MgAlF5 ·2H2 O captures polysulfides by chemisorption to suppress the shuttle effect. Therefore, a 1.97 A h-level Li-S pouch cell achieves a high WG of 386 Wh kg-1 . This work develops a new-type ionic conductor, and provides unique insights and new hosts for designing practical Li-S pouch cells.

Study Protocol of a Multicenter, Randomized, Single-Blind Trial: Efficacy and Safety of Remimazolam Tosylate for Sedation in ICU Patients.

INTRODUCTION: Pharmacodynamic and pharmacokinetic studies in animal experiments and a phase 1 study suggested remimazolam tosylate as an effective and safe sedation/anesthetic agent. However, the effects and safety dose of remimazolam for light sedation in intensive care unit (ICU) patients are not clear and should be confirmed in a phase 2 study. METHODS: Sixty ICU patients requiring sedation treatment and undergoing mechanical ventilation will be enrolled and randomly assigned to a high dose group (HD group, 30 cases) and a low dose group (LD group, 30 cases) in a 1:1 ratio. Patients in both groups will be sedated using remimazolam tosylate in a primary dose of 0.08 mg/kg and a range of 0-2.0 mg/kg/h after randomization. Dose adjustment will be made at the range of every 0.1 mg/kg/h in the LD group and 0.2 mg/kg/h in the HD group to maintain the target Richmond Agitation and Sedation Score (RASS) at - 2 to + 1. The primary outcome will be the proportion of subjects that meet the following conditions: the time within the range of RASS (- 2 to + 1) accounts for 70% of the study drug administration time; without other rescue treatments. Secondary outcomes including the percentage time to reach the sedation goal; the proportion of subjects receiving rescue sedation and/or analgesic, and the mean dose of rescue drug throughout the study period; duration of mechanical ventilation; recovery time to full consciousness and nursing scores. Evaluations of safety including adverse events (AEs), serious AEs, physical examination, laboratory examination, etc. OUTCOME: The results of this study will provide crucial information for the use of remimazolam tosylate for ICU sedation. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT05152303.

A fuzzy DRBFNN-based information security risk assessment method in improving the efficiency of urban development.

The rapid development of urban informatization is an important way for cities to achieve a higher pattern, but the accompanying information security problem become a major challenge restricting the efficiency of urban development. Therefore, effective identification and assessment of information security risks has become a key factor to improve the efficiency of urban development. In this paper, an information security risk assessment method based on fuzzy theory and neural network technology is proposed to help identify and solve the information security problem in the development of urban informatization. Combined with the theory of information ecology, this method establishes an improved fuzzy neural network model from four aspects by using fuzzy theory, neural network model and DEMATEL method, and then constructs the information security risk assessment system of smart city. According to this method, this paper analyzed 25 smart cities in China, and provided suggestions and guidance for information security control in the process of urban informatization construction.

Characteristics and Prognostic Analysis of 55 Patients With Pulmonary Sarcomatoid Carcinoma.

Pulmonary sarcomatoid carcinoma (PSC) is a rare and aggressive subtype of non-small-cell lung cancer (NSCLC). Here, we present information on the clinicopathologic characteristics and clinical outcomes of this type of cancer. Clinicopathologic data from 55 patients treated at a single cancer center from January 2011 to December 2018 were retrospectively analyzed. The patients were mostly male (76.4%), with a median age of 66 years and a history of smoking (54.5%). Most had symptoms, and about 60% presented with locally advanced or metastatic disease at diagnosis. Of the 55 cases, 21 were diagnosed by surgical resection. Pleomorphic cancer was the most common subtype (58.1%). With a median follow-up period of 13.2 months, the average survival time of the patients was 16.1 months, and the median survival time was 12 months. The overall survival rates for 1, 2, and 3 years were 52.7%, 18.2%, and 9.1%, respectively. Univariate analysis showed that prognosis of the patients was influenced by tumor size, T stage, metastatic status, and surgery (p < 0.05). Multivariate analysis showed that T stage (p = 0.034) was an independent prognostic factor. There are few reports on the natural history of PSC, and its clinicopathological characteristics remain unclear. Herein, a retrospective review 55 individuals with PSC found that T stage was an independent predictor of survival. Surgical resection was associated with better prognosis.

Mining of a Clinical Database: The Interpretation of Intense Serial Procalcitonin in the Prediction for Bloodstream Infection.

Background: Procalcitonin (PCT) is a promising biomarker for predicting infection. Bloodstream infection (BSI) is usually a deteriorating stage of sepsis. The purpose of this study was to explore the predictive value of intense serial PCT assays for BSI in the intensive care unit (ICU). Methods: This study was a retrospective study based on a clinical database. We analyzed the data of critically ill patients from February 2016 to May 2020. The patients who received PCT assays and blood cultures (BCs) were classified into four groups according to the BCs: (i) BC negative, (ii) bacteria positive, (iii) fungi-positive, and (iv) combined-positive, and the patients with bacteremia were further subdivided into Gram+ and Gram- bacteremia. Results: The database included 11,219 patients. There were 3,593 patients who met the criteria for the analysis. The PCT concentration differed significantly across BC groups (p < 0.0001). The fluctuation of PCT significantly increased in the BC positive groups (p < 0.0001). According to the receiver operating characteristic (ROC), the optimum cutoff of the fluctuation of PCT was around 8 ng/ml for predicting BSI. Conclusion: Our study indicated that the fluctuation of PCT could be an indicator for screening BSI, but less accurate for Gram-positive infections. With a fluctuation of PCT less than 8 ng/ml, BSI should not be a rational cause for sepsis exacerbating.

[Effect of ethyl pyruvate on mitochondrial dynamics of lipopolysaccharide-induced human kidney-2 cells].

OBJECTIVE: To examine the effects of ethyl pyruvate (EP) on mitochondrial dynamics and cell apoptosis in lipopolysaccharide (LPS)-induced human kidney-2 (HK-2) cells. METHODS: HK-2 cells were divided into three groups: HK-2 cells were challenged with LPS (800 µg/L) for 24 hours as LPS group, or LPS mixed with EP (0.25 mmol/L) for 24 hours as EP group. Cells were incubated with normal saline for 24 hours as control group. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and intracellular adenosine triphosphate (ATP) were detected by enzyme linked immunosorbent assay (ELISA). JC-1 staining and Annexin V-fluorescein isothiocyanate/propidium iodide (FITC/PI) assays were used to evaluate mitochondrial membrane potential and cell apoptosis, respectively. Western Blot was used to evaluate the protein expressions of mitochondrial dynamics, including death-associated protein kinase 2 (DAPK-2), mitofusin (Mfn-1 and Mfn-2), and apoptotic associated biomarkers, including caspase-3, caspase-9, Bcl-2, Bcl-xL, cytochrome C (Cyt C), and DNA repair enzyme poly ADP-ribose polymerase (PARP). RESULTS: Compared with the NC group, MDA, IL-6, TNF-α of LPS group were significantly increased, the expression of SOD, mitochondrial membrane potential and ATP level were significantly decreased, the expression of mitochondrial fission protein DAPK-2 was significantly increased, and mitochondrial fusion proteins Mfn-1 and Mfn-2 were significantly decreased, cell apoptosis and apoptotic protein caspase-3, caspase-9 and Cyt C were increased, and anti-apoptotic protein Bcl-2, Bcl-xL, PARP were significantly decreased. Compared with the LPS group, the oxidative activities and inflammatory factors above were inhibited in EP group [MDA (µmol/L): 12.35±2.21 vs. 45.95±1.76, SOD (kU/L): 54.68±1.42 vs. 40.73±1.60, IL-6 (ng/L): 67.87±2.61 vs. 338.92±20.91, TNF-α (ng/L): 19.23±1.80 vs. 180.69±6.51], mitochondrial membrane potential and ATP level were significantly increased [mitochondrial membrane potential: (99.43±0.25)% vs. (69.40±0.75)%, ATP (×106 RLU): 0.19±0.01 vs. 0.12±0.05], the expression of mitochondrial fission protein was significantly decreased (DAPK-2/ß-actin: 0.03±0.01 vs. 0.61±0.02), mitochondrial fusion proteins were significantly increased (Mfn-1/ß-actin: 0.43±0.04 vs. 0.17±0.01, Mfn-2/ß-actin: 0.201±0.004 vs. 0.001±0.001), percentage of cell apoptosis was significantly decreased [(5.25±0.17)% vs. (34.42±0.64)%], the expressions of apoptotic proteins were significantly decreased (caspase-3/ß-actin: 0.25±0.15 vs. 1.76±0.01, caspase-9/ß-actin: 0.09±0.02 vs. 1.52±0.12, Cyt C/ß-actin: 0.001±0.001 vs. 0.350±0.030), and the expressions of anti-apoptotic proteins and PARP were significantly increased (Bcl-2/ß-actin: 0.500±0.010 vs. 0.009±0.004, Bcl-xL/ß-actin: 0.550±0.010 vs. 0.009±0.001, PARP/ß-actin: 0.94±0.01 vs. 0.16±0.13), with statistically significant differences (all P < 0.05). CONCLUSIONS: There are enhanced mitochondrial fission and diminished mitochondrial fusion in LPS-induced HK-2 cells. EP can protect mitochondria functions by regulate mitochondrial dynamics, and reducethe apoptosis of LPS-induced HK-2 cells.

miR­23a downregulation modulates the inflammatory response by targeting ATG12­mediated autophagy.

Autophagy, part of the innate immune defense mechanisms, is activated during the initial phase of septic insult. Previous studies indicated that micro (mi)RNAs are additionally involved in the host response to sepsis; however, the association between miRNAs and autophagy during this process is not fully understood. To study the role of miRNA (miR)­23a in autophagy initiated by sepsis, macrophages treated with lipopolysaccharides, in addition to blood samples from patients, were evaluated for miR­23a expression levels. Cell viability, inflammatory mediators and autophagic markers were investigated following overexpression or inhibition of miR­23a. The results suggested that miR­23a was suppressed subsequent to septic insult, promoting autophagy and suppressing a hyper inflammatory response, leading to enhanced cell viability. A luciferase assay and western blot analysis confirmed ubiquitin­like protein ATG12 to be the target of miR­23a. The present study revealed that the downregulation of miR­23a regulates an inflammatory response during septic insult via autophagy promotion.

MiR-320a-3p/ELF3 axis regulates cell metastasis and invasion in non-small cell lung cancer via PI3K/Akt pathway.

MicroRNAs (miRNAs) play important roles in tumorigenesis and tumor progression. In this study, we investigated the role of miR-320a-3p in non-small cell lung cancer (NSCLC). Expressions of miR-320a-3p were firstly determined in 80 NSCLC patients' cancer tissues and adjacent normal lung tissues by qRT-PCR. Then MTT assay, cell migration and invasion assays were performed in vitro. Potential binding sites on target gene of miR-320a-3p were predicted and luciferase reporter assay was used to identify the potential binding sites. Tumorigenesis assay were performed in nude mice by injecting A549 cells which stably express miR-320a-3p. Results indicated that high expression of miR-320a-3p suppresses cell proliferation, migration and invasion through the inactivation of PI3K/Akt signaling pathway in NSCLC cells. Smaller tumor size and lighter weight were also found in nude mice which had miR-320a-3p higher expressed. Furthermore, data from luciferase reporter assay proved the direct binding of miR-320a-3p on the 3'UTR region of ELF3 mRNA, this could further decrease ELF3 expression transcriptionally. We provided evidence that miR-320a-3p might work as a tumor suppressor in NSCLC both in vivo and in vitro.

Human trypsin inhibitor reduces the apoptosis of lipopolysaccharide­induced human kidney­2 cells by promoting mitochondrial fusion.

Imbalance in mitochondrial fusion/fission is one of the mechanisms leading to sepsis­induced mitochondrial dysfunction and cell apoptosis. The present study examined the effects of human trypsin inhibitor (UTI), a well­known antioxidant and anti­inflammatory substance, on mitochondrial dynamics and cell apoptosis in lipopolysaccharide (LPS)­induced human kidney­2 (HK­2) cells. The HK­2 cells were incubated for 24 h either with LPS (800 ng/ml) or LPS (800 ng/ml) mixed with UTI (250 U/ml). Cell viability was assessed using a3­(4,5­dimethyl­2­thiazolyl)­2, 5­diphenyl­2­H­tetrazolium bromide assay. Oxidative activities (estimated by maleic dialdehyde and superoxide dismutase), levels of inflammatory cytokines interleukin (IL)­6 and tumor necrosis factor (TNF)­α, and levels of ATP were measured using an enzyme­linked immunosorbent assay. The expression levels of the mitochondrial fission protein, death­associated protein kinase 2 (DAPK­2), mitofusin (Mfn)1 and Mfn2 mitochondrial fusion proteins, and apoptotic and anti­apoptotic biomarkers, including cytochrome c, caspase­3, caspase­9, B­cell lymphoma (Bcl)­2, Bcl­extra large and poly ADP­ribose polymerase (PARP), were assessed using western blot analyses. The changes in mitochondrial membrane potential were analyzed following JC­1 staining. Annexin V/propidium iodide assays were used to evaluate cell apoptosis. The results showed that the balance of mitochondrial dynamics was towards mitochondrial fusion in the UTI group, as a reduced expression of DAPK2, and increased expression levels of Mfn1 and Mfn2 were detected (P<0.05, vs. LPS group). In addition, adecline in the levels of the inflammatory cytokines, TNF­α and IL­6, and the oxidative activities, reflected by an increase in SOD and a decrease in MDA (P<0.05, vs. LPS group) were observed. Cell apoptosis was inhibited following co­treatment with UTI (P<0.05, vs. LPS group). It was concluded that UTI may protect mitochondrial functions by promoting mitochondrial fusion and limiting mitochondrial fission, thus reducing the apoptosis of LPS­induced HK­2 cells.

Terlipressin protects intestinal epithelial cells against oxygen-glucose deprivation/re-oxygenation injury via the phosphatidylinositol 3-kinase pathway.

Intestinal ischemia/reperfusion (I/R) injury is associated with a high morbidity and mortality. Vasopressin is administered to critically ill patients with potential intestinal I/R. However, the impacts of vasopressin on intestinal epithelia under ischemic/anoxic conditions remain unclear. The aim of the present study was to evaluate the effects of terlipressin, a highly selective vasopressin V1 receptor agonist, on oxygen and glucose deprivation/re-oxygenation (OGD/R)-induced damage in intestinal epithelial cells (IEC-6). IEC-6 cells were subjected to OGD for 4 h, followed by 4 h re-oxygenation. Terlipressin was incubated with cells for 4 h following OGD. Following OGD/R, IEC-6 cell viability, proliferation and apoptosis, as well as cell cycle dynamics, were assessed and the levels of tumor necrosis factor (TNF)-α and 15-F2t-isoprostane in the culture medium were measured. In addition, wortmannin, a specific phosphatidylinositol 3-kinase (PI3K) inhibitor, was administrated to investigate the mechanism of terlipressin action. The results demonstrated that IEC-6 cell viability and proliferation decreased, and cell apoptosis increased, following OGD/R. However, IEC-6 cell cycle dynamics did not significantly change 4 h after OGD. Incubation with 25 nM terlipressin significantly improved cell viability, proliferation and apoptosis. Furthermore, terlipressin inhibited the secretion of TNF-α and 15-F2t-isoprostane from IEC-6 cells following OGD/R. The aforementioned effects of terlipressin were completely abolished following the application of 2 µM wortmannin. Therefore, the current study demonstrated that terlipressin administration following OGD attenuates OGD/R-induced cell damage via the PI3K signaling pathway. These results may help physicians to better understand and more effectively use terlipressin in a clinical setting.

[Current Status of Middle East Respiratory Syndrome Vaccines].

Middle East respiratory syndrome is a kind of respiratory disease Caused by Middle East respiratory syndrome Coronavirus. Now the disease has spread to 27 countries around the world, more than 1806 people infected and more than 600 people were killed, and four countries have reported cases of camel infection MERS. Prevention of the disease are very important measures to research and development related to the vaccine. In order to have more resources into the development of safe and effective vaccine, this article summarizes the current some candidate vaccine of MERS research progress for the prevention and treatment of the disease that could trigger a global public health security problems ahead.

Ethyl pyruvate reduces hepatic mitochondrial swelling and dysfunction in a rat model of sepsis.

Sepsis causes mitochondrial oxidative injury and swelling. Ethyl pyruvate (EP) is a cytoprotective agent, while aquaporin-8 (AQP8) is a mitochondrial water channel that can induce mitochondrial swelling. We assessed whether EP protects mitochondria during sepsis, and whether AQP8 contributes to the underlying mechanisms. A cecal ligation and puncture (CLP) sepsis model was established in Sprague-Dawley rats, randomized to 3 groups: sham (n=20), CLP (n=59) and CLP+EP (n=51). All rats received postoperative intraperitoneal fluid resuscitation (30 ml/kg); the CLP+EP group also received intraperitoneal EP (100 mg/kg). Survival was assessed at 24 hours. Hepatic mitochondrial ultrastructure was characterized by electron microscopy. The membrane potential of isolated hepatic mitochondria was determined using JC-1 and flow cytometry. Mitochondrial AQP8 expression and cytochrome C (Cyt C) release were measured by Western blotting (values normalized to ß-actin). Survival in the sham, CLP and CLP+EP groups was 100%, 21% and 41%, respectively. Mitochondrial cross-sectional area was smaller in the CLP+EP group than in the CLP group (0.231±0.110 vs. 0.641±0.460 µm(2); P<0.001), with a tendency for a lower form factor (a measure of contour irregularity) in the CLP+EP group. Mitochondrial depolarization by CLP was inhibited by EP. Mitochondrial Cyt C release was higher in the CLP group than in the sham (1.211±0.24 vs. 0.48±0.03) or CLP+EP (0.35±0.39) groups. AQP8 expression was similar between groups, with a trend for lower expression in the CLP+EP group compared with the CLP group. EP improves sepsis outcome by targeting the mitochondrion, possibly through modulation of AQP8 expression.

MiR-204/miR-211 downregulation contributes to candidemia-induced kidney injuries via derepression of Hmx1 expression.

AIMS: This study was aimed to exploit the role of heme oxygenase Hmx1 and the potential miRNA mechanisms in the kidney injuries induced by urinary tract infection by Candida species/Candidemia. MAIN METHODS: We employed a mouse model of systemic Candidiasis by injection of the Candida albicans strain SC5314 into C57BL/6 mice. Kidney injuries were assessed by measuring serum cystatin C (CysC), serum ß2-microglobulin (ß2-MG) and blood urea nitrogen (BUN). Validation of miRNA target gene was conducted by luciferase reporter gene assay, Western blot analysis and real-time RT-PCR. KEY FINDINGS: We showed here that Candidemia caused significant downregulation of microRNAs miR-204 and miR-211. In sharp contrast, Hmx1 expression was remarkably upregulated, particularly at the protein level. Computational analysis predicted Hmx1 as a target gene for both miR-204 and miR-211 that share the same seed site sequence. We then experimentally validated the targeting relationship between miR-204/miR-211 and Hmx1, which explains the reciprocal changes of expression of miR-204/miR-211 and Hmx1 in Candidemia. Administration of miR-204/miR-211 mimics substantially downregulated Hmx1 and mitigated the severity of the kidney injuries induced by Candidemia, as reflected by improved renal glomerular filtration rate (GFR) determined by serum cystatin C (CysC), serum ß2-microglobulin (ß2-MG) and blood urea nitrogen (BUN). Knockdown of miR-204/miR-211 worsened while forced expression of miR-204/miR-211 ameliorated kidney injuries in mice with systemic Candidiasis. SIGNIFICANCE: Our findings indicate that miR-204/miR-211 downregulation accounts at least partially for the Hmx1 upregulation and the miR-204/miR-211-Hmx1 signaling axis may contribute to immune-suppression in the host thereby the Candidemia-induced kidney dysfunction.

[Clinical research for trough value of serum vancomycin in critical patients].

OBJECTIVE: To observe the changes in serum vancomycin trough concentration, and explore its optimal dosage in critical patients. METHODS: A retrospective study was conducted. Data of 66 patients who used vancomycin during July 2010 to May 2012 in surgical intensive care unit (SICU) of the First Affiliated Hospital of Sun Yat-Sen University were collected and analyzed. According to the endogenous creatinine clearance rate (CCr), the patients were divided into two groups: CCr normal group (≥70 mL/min) and CCr lowered group (<70 mL/min). The distribution of vancomycin serum trough concentration between two groups, relationship between vancomycin serum trough concentrations and CCr, and the influence of vancomycin serum trough concentrations on the prognosis was analyzed. The difference between actual dosage and the recommended dosage in guideline was compared between two groups. RESULTS: 119 times of vancomycin serum trough concentration in 66 patients were enrolled, and it was found that only 20.17% (24/119) reached the target concentration (15-20 mg/L), 45.38% (54/119)<15 mg/L and 34.45% (41/119) >20 mg/L. Vancomycin serum trough concentration in CCr normal group (55 cases) was (13.11±6.84) mg/L, among them 65.5% (36/55) attained lower trough concentrations (<15 mg/L). In the subgroup with 15-20 mg/L trough serum concentrations, vancomycin doses were significantly lower than that of recommendation (1.95±0.61 g/d vs. 2.73±0.32 g/d, F=1.739, P=0.001). Vancomycin serum trough concentration in CCr lowered group (64 cases) was (20.49±8.12) mg/L, with 51.5% (33/64) of them showed higher trough concentrations (>20 mg/L). In the subgroup with 15-20 mg/L vancomycin trough serum concentration, vancomycin doses were higher than that of recommendation (1.08±0.49 g/d vs. 0.78±0.19 g/d, F=11.294, P=0.062). There was no significant difference in 28-day mortality between patients with targeting trough serum concentrations and those without [22.2% (4/18) vs. 18.8% (9/48), χ(2)=0.009, P=0.924]. Serum creatinine [odds ratio (OR)=1.001, 95% confidence interval (95%CI): 0.990-1.012, P=0.000], vancomycin doses (OR=0.600, 95%CI: 0.251-1.434, P=0.003), age (OR=0.985, 95%CI: 0.955-1.015, P=0.015) and body mass index (OR=1.013, 95%CI: 0.967-1.062, P=0.022) were found to be correlated to serum trough concentrations by multiple linear regression analysis. CONCLUSIONS: The rate of vancomycin serum trough concentrations reaching the standard is low in critical patients, so constant monitoring is necessary. Creatinine, vancomycin dosage, age and body mass index show a relatively significant influence on the serum trough concentrations, and they should be taken into consideration in dosage to be given.