Efficacy and Safety of Ciprofol Sedation in ICU Patients Undergoing Mechanical Ventilation: A Multicenter, Single-Blind, Randomized, Noninferiority Trial.

OBJECTIVES: To determine the effectiveness and safety of ciprofol for sedating patients in ICUs who required mechanical ventilation (MV). DESIGN: A multicenter, single-blind, randomized, noninferiority trial. SETTING: Twenty-one centers across China from December 2020 to June 2021. PATIENTS: A total of 135 ICU patients 18 to 80 years old with endotracheal intubation and undergoing MV, who were expected to require sedation for 6-24 hours. INTERVENTIONS: One hundred thirty-five ICU patients were randomly allocated into ciprofol ( n = 90) and propofol ( n = 45) groups in a 2:1 ratio. Ciprofol or propofol were IV infused at loading doses of 0.1 mg/kg or 0.5 mg/kg, respectively, over 4 minutes ± 30 seconds depending on the physical condition of each patient. Ciprofol or propofol were then immediately administered at an initial maintenance dose of 0.3 mg/kg/hr or 1.5 mg/kg/hr, to achieve the target sedation range of Richmond Agitation-Sedation Scale (+1 to -2). Besides, continuous IV remifentanil analgesia was administered (loading dose: 0.5-1 µg/kg, maintenance dose: 0.02-0.15 µg/kg/min). MEASUREMENTS AND MAIN RESULTS: Of the 135 patients enrolled, 129 completed the study. The primary endpoint-sedation success rates of ciprofol and propofol groups were 97.7% versus 97.8% in the full analysis set (FAS) and were both 100% in per-protocol set (PPS). The noninferiority margin was set as 8% and confirmed with a lower limit of two-sided 95% CI for the inter-group difference of -5.98% and -4.32% in the FAS and PPS groups. Patients who received ciprofol had a longer recovery time ( p = 0.003), but there were no differences in the remaining secondary endpoints (all p > 0.05). The occurrence rates of treatment-emergent adverse events (TEAEs) or drug-related TEAEs were not significantly different between the groups (all p > 0.05). CONCLUSIONS: Ciprofol was well tolerated, with a noninferior sedation profile to propofol in Chinese ICU patients undergoing MV for a period of 6-24 hours.

Closo-[B12 H12 ]2- Derivatives with Polar Groups As Promising Building Blocks in Metal-Organic Frameworks for Gas Separation.

Engineering design of metal organic frameworks (MOFs) for gas separation applications is nowadays a thriving field of investigation. Based on the recent experimental studies of dodecaborate-hybrid MOFs as potential materials to separate industry-relevant gas mixtures, we herein present a systematic theoretical study on the derivatives of the closo-dodecaborate anion [B12 H12 ]2- , which can serve as building blocks for MOFs. We discover that amino functionalization can impart a greater ability to selectively capture carbon dioxide from its mixtures with other gases such as nitrogen, ethylene and acetylene. The main advantage lies in the polarization effect induced by amino group, which favors the localization of the negative charges on the boron-cluster anion and offers a nucleophilic anchoring site to accommodate the carbon atom in carbon dioxide. This work suggests an appealing strategy of polar functionalization to optimize the molecule discrimination ability via preferential adsorption.

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.

Intestinal recruitment of CCR6-expressing Th17 cells by suppressing miR-681 alleviates endotoxemia-induced intestinal injury and reduces mortality.

INTRODUCTION: Sepsis or endotoxemia can induce intestinal dysfunction in the epithelial and immune barrier. Th17 cells, a distinct subset of CD4+ T-helper cells, act as "border patrol" in the intestine under pathological condition and in the previous studies, Th17 cells exhibited an ambiguous function in intestinal inflammation. Our study will explore a specific role of Th17 cells and its relevant mechanism in endotoxemia-induced intestinal injury. MATERIALS AND METHODS: Lipopolysaccharide was used to establish mouse model of endotoxemia. miR-681 was analyzed by RT-PCR and northern blot analysis and its regulation by HIF-1α was determined by chromatin immunoprecipitation and luciferase reporter assay. Intestinal Th17 cells isolated from endotoxemic mice were quantitatively evaluated by flow cytometry and its recruitment to the intestine controlled by miR-681/CCR6 pathway was assessed by using anti-miRNA treatment and CCR6 knockout mice. Intestinal histopathology, villus length, intestinal inflammation, intestinal permeability, bacterial translocation and survival were investigated, by histology and TUNEL analysis, ELISA, measurement of diamine oxidase, bacterial culture, with or without anti-miR-681 treatment in endotoxemic wild-type and (or) CCR6 knockout mice. RESULTS: In this study, we found that miR-681 was significantly promoted in intestinal Th17 cells during endotoxemia, which was dependent on hypoxia-inducible factor-1α (HIF-1α). Interestingly, miR-681 could directly suppress CCR6, which was a critical modulator for Th17 cell recruitment to the intestines. In vivo, anti-miR-681 enhanced survival, increased number of intestinal Th17 cells, reduced crypt and villi apoptosis, decreased intestinal inflammation and bacterial translocation, resulting in protection against endotoxemia-induced intestinal injury in mice. However, CCR6 deficiency could neutralize the beneficial effect of anti-miR-681 on the intestine during endotoxemia, suggesting that the increment of intestinal Th17 cells caused by anti-miR-681 relies on CCR6 expression. CONCLUSION: The results of the study indicate that control of intestinal Th17 cells by regulating novel miR-681/CCR6 signaling attenuates endotoxemia-induced intestinal injury.

The Multiple Influences of Natural Farming Environment on the Cultured Population Behavior of Kuruma Prawn, Penaeus japonicus.

Recent years have witnessed a tremendous development in shrimp farming around the world, which, however, has raised a variety of issues, possibly due to a lack of knowledge of shrimp behavior in farms. This study focused on the relationship between shrimp behavior and the various factors of natural farming environment through situ surveys, as distinguished from the majority of laboratory studies on shrimp behavior. In the survey, the behaviors of kuruma prawn (Penaeus japonicus) were investigated in the groups of swimming in the water, crawling on the sand, resting on the sand, and hiding in the sand, followed by the quantification of the sex ratio, water quality, density, and light intensity. The results showed the average proportions of resting, hiding, crawling, and swimming activities of 69.87%, 20.85%, 8.24%, and 1.04%, respectively, of P. japonicus. The behavior of hiding, resting, and crawling is significantly affected by the sex ratio of the shrimp (p < 0.05). The proportions of hiding behavior exhibited a negative connection with density and a positive connection with light intensity, while the proportions of resting behavior showed the opposite according to both Pearson correlation analysis and multiple linear regression analysis. The light intensity was the only factor that significantly influenced the swimming behavior, in which the probability of the swimming behavior was reduced from 48% to 5% when light intensity varied from 0 to 10 lx, as determined by the generalized linear model. It could be speculated that P. japonicus prefers a tranquil environment. Female shrimp might exhibit less aggression and more adventure compared to male shrimp. The findings suggested light intensity, followed by density, as the most crucial element influencing the behavior of P. japonicus in the culture environment. These findings will contribute to the comprehension of the behavior of P. japonicus and provide a novel perspective for the formulation of its culture management strategy.

Seasonal variations and co-occurrence networks of bacterial communities in the water and sediment of artificial habitat in Laoshan Bay, China.

Marine bacteria in the seawater and seafloor are essential parts of Earth's biodiversity, as they are critical participants of the global energy flow and the material cycles. However, their spatial-temporal variations and potential interactions among varied biotopes in artificial habitat are poorly understood. In this study, we profiled the variations of bacterial communities among seasons and areas in the water and sediment of artificial reefs using 16S rRNA gene sequencing, and analyzed the potential interaction patterns among microorganisms. Distinct bacterial community structures in the two biotopes were exhibited. The Shannon diversity and the richness of phyla in the sediment were higher, while the differences among the four seasons were more evident in the water samples. The seasonal variations of bacterial communities in the water were more distinct, while significant variations among four areas were only observed in the sediment. Correlation analysis revealed that nitrite and mud content were the most important factors influencing the abundant OTUs in the water and sediment, respectively. Potential interactions and keystone species were identified based on the three co-occurrence networks. Results showed that the correlations among bacterial communities in the sediment were lower than in the water. Besides, the abundance of the top five abundant species and five keystone species had different changing patterns among four seasons and four areas. These results enriched our understanding of the microbial structures, dynamics, and interactions of microbial communities in artificial habitats, which could provide new insights into planning, constructing and managing these special habitats in the future.

Safety and efficacy of ciprofol vs. propofol for sedation in intensive care unit patients with mechanical ventilation: a multi-center, open label, randomized, phase 2 trial.

BACKGROUND: Ciprofol (HSK3486; Haisco Pharmaceutical Group Co., Ltd., Chengdu, China), developed as a novel 2,6-disubstituted phenol derivative showed similar tolerability and efficacy characteristics as propofol when applicated as continuous intravenous infusion for 12 h maintenance sedation in a previous phase 1 trial. The phase 2 trial was designed to investigate the safety, efficacy, and pharmacokinetic characteristics of ciprofol for sedation of patients undergoing mechanical ventilation. METHODS: In this multicenter, open label, randomized, propofol positive-controlled, phase 2 trial, 39 Chinese intensive care unit patients receiving mechanical ventilation were enrolled and randomly assigned to a ciprofol or propofol group in a 2:1 ratio. The ciprofol infusion was started with a loading infusion of 0.1-0.2 mg/kg for 0.5-5.0 min, followed by an initial maintenance infusion rate of 0.30 mg·kg -1 ·h -1 , which could be adjusted to an infusion rate of 0.06 to 0.80 mg·kg -1 ·h -1 , whereas for propofol the loading infusion dose was 0.5-1.0 mg/kg for 0.5-5.0 min, followed by an initial maintenance infusion rate of 1.50 mg·kg -1 ·h -1 , which could be adjusted to 0.30-4.00 mg·kg -1 ·h -1 to achieve -2 to +1 Richmond Agitation-Sedation Scale sedation within 6-24 h of drug administration. RESULTS: Of the 39 enrolled patients, 36 completed the trial. The median (min, max) of the average time to sedation compliance values for ciprofol and propofol were 60.0 (52.6, 60.0) min and 60.0 (55.2, 60.0) min, with median difference of 0.00 (95% confidence interval: 0.00, 0.00). In total, 29 (74.4%) patients comprising 18 (69.2%) in the ciprofol and 11 (84.6%) in the propofol group experienced 86 treatment emergent adverse events (TEAEs), the majority being of severity grade 1 or 2. Drug- and sedation-related TEAEs were hypotension (7.7% vs. 23.1%, P  = 0.310) and sinus bradycardia (3.8% vs. 7.7%, P  = 1.000) in the ciprofol and propofol groups, respectively. The plasma concentration-time curves for ciprofol and propofol were similar. CONCLUSIONS: ciprofol is comparable to propofol with good tolerance and efficacy for sedation of Chinese intensive care unit patients undergoing mechanical ventilation in the present study setting. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04147416.

SIRT3 Regulates Neuronal Excitability of Alzheimer's Disease Models in an Oxidative Stress-Dependent Manner.

Mitochondrial deacetylase Sirtuin-3 (SIRT3) has been shown to regulate metabolic and antioxidant functions. Previous studies have reported that SIRT3 mediates change of neuronal excitability. However, the underlying mechanism is unclear. Here, we show that SIRT3 deficiency results in neural hyperactivity, decreased survival rate, and increased oxidative stress of culture neurons, while a superoxide dismutase 2 mimetic reduces oxidative stress and suppresses the neuronal hyperactivity. In culture neurons treated with Aß, SIRT3 activator reduces level of reactive oxygen species (ROS) and hyperactivity of neurons while increasing level of ROS restores the neuronal hyperactivity. Utilizing two photon in vivo brain imaging, we show that inhibition of SIRT3 results in elevated neuronal excitatory in an animal model of Alzheimer's disease of early stage, whereas suppression of the ROS level reverses it. These findings demonstrate an oxidative stress-dependent role of SIRT3 in regulation of neuronal excitability in Alzheimer's disease.

Efficacy and Safety of Ciprofol Sedation in ICU Patients with Mechanical Ventilation: A Clinical Trial Study Protocol.

INTRODUCTION: From previous studies of pharmacodynamic data in mice, rats, beagle dogs and mini pigs, frequently in direct comparison to induction doses of propofol, ciprofol produced a rapid onset of anesthesia/sedation. METHODS: A phase 1 study suggested potential clinical advantages of ciprofol as a sedation/anesthetic agent, with no evidence of drug-related toxicity. However, the sedation effects and safety of ciprofol in intensive care unit (ICU) patients with mechanical ventilation should be further confirmed in a phase 3 study with a larger cohort of patients. During a phase 3, non-inferiority, multicenter, single-blind, randomized, propofol controlled trial, Chinese ICU patients undergoing mechanical ventilation and requiring endotracheal intubation will be sedated for 6-24 h after randomization. Considering a success rate for ICU sedation of 99% for ciprofol and the positive control drug propofol, a total sample size of 120 subjects with mechanical ventilation will be required to achieve 80% power to determine non-inferiority with a margin of 8%. Finally, taking into account 10% losses, 135 patients will be enrolled and randomly assigned to ciprofol (90 cases) and propofol (45 cases) groups in a 2:1 ratio. The primary outcome will be the success rate of sedation satisfied by the following conditions: the time within the range of Richmond Agitation and Sedation Score (+ 1 ~ - 2) must account for ≥ 70% of the study drug administration time and without other rescue treatments. Secondary outcomes will include the average time to reach the sedation goal, study drug usage, rescue medication given per unit weight, extubation time, recovery time to full consciousness and nursing scores. Safety endpoints will include adverse events (AEs), drug related AEs and serious AEs. PLANNED OUTCOMES: The results of this study will provide crucial information on the use of ciprofol for sedation of patients in ICUs. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04620031.

Optimizing the sulfonic groups of a polymer to coat the zinc anode for dendrite suppression.

The zinc metal anodes in aqueous zinc-ion batteries suffer from low cycling performance caused by uncontrolled dendrite. We have designed sulfonated poly-ether-ether-ketone (SPEEK) polymers as a surface coating layer on the zinc anode for dendrite suppression, in which the sulfonic groups in polymers act as effective active sites for zinc-ion diffusion. In SPEEK, the un-sulfonated domain serves as the framework and the sulfonated domain serves as the functional part to re-distribute the zinc ions. By optimizing the degree of SPEEK sulfonation, the best zinc anode coating has been achieved to present a high reversibility of over 1600 hours in symmetric cells and improved performance in full cells.

Mesenteric Lymph Duct Drainage Attenuates Lung Inflammatory Injury and Inhibits Endothelial Cell Apoptosis in Septic Rats.

The present study was to investigate the effect of mesenteric lymph duct drainage on lung inflammatory response, histological alteration, and endothelial cell apoptosis in septic rats. Animals were randomly assigned into four groups: control, sham surgery, sepsis, and sepsis plus mesenteric lymph drainage. We used the colon ascendens stent peritonitis (CASP) procedure to induce the septic model in rats, and mesenteric lymph drainage was performed with a polyethylene (PE) catheter inserted into mesenteric lymphatic. The animals were sacrificed at the end of CASP in 6 h. The mRNA expression levels of inflammatory mediators were measured by qPCR, and the histologic damage were evaluated by the pathological score method. It was found that mesenteric lymph drainage significantly reduced the expression of TNF-α, IL-1ß, and IL-6 mRNA in the lung. Pulmonary interstitial edema and infiltration of inflammatory cells were alleviated by mesenteric lymph drainage. Moreover, increased mRNA levels of TNF-α, IL-1ß, IL-6 mRNA, and apoptotic rate were observed in PMVECs treated with septic lymph. These results indicate that mesenteric lymph duct drainage significantly attenuated lung inflammatory injury by decreasing the expression of pivotal inflammatory mediators and inhibiting endothelial apoptosis to preserve the pulmonary barrier function in septic rats.

[Clinical study of D-lactate and intestinal fatty acid binding protein in evaluating disease severity and prognosis of ICU patients: secondary analysis of a prospective, multicenter clinical study].

OBJECTIVE: To analyze the relationship between D-lactate, intestinal fatty acid binding protein (I-FABP) and the severity as well as the prognosis of patients in intensive care unit (ICU). METHODS: Using a retrospective approach, the data derived from a prospective, randomized, single-blind, multicenter clinical study published earlier by our group were further analyzed to evaluate the effect of fat-modified enteral nutrition (EN) suspension on the intestinal barrier in ICU patients. In this study, a total of 141 patients were recruited from 7 ICUs in South China, and 15 healthy volunteers were included as healthy control group. Clinical data of patients were collected, including gender, age, disease severity related indicators such as acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), C-reactive protein (CRP) and initial ICU diagnosis, as well as prognostic indicators such as length of stay in ICU, length of stay in hospital and prognosis of patients at 28 days. To compare the difference of serum D-lactate and I-FABP between ICU patients and healthy control group on day 0 (the day before EN reached 500 mL) and day 5 (EN ≥ 2 092 kJ/d for 5 days). According to the hemodynamic and/or mechanical ventilation status on day 5 (compared with day 0), 141 patients were divided into the improvement group (101 cases) and the non-improvement group (40 cases), and the changes of D-lactate and I-FABP in the two groups were observed. Spearman correlation analysis was used to analyze the correlation between serum D-lactate, I-FABP and the severity of the disease, as well as the predictive value of dynamic changes of D-lactate and I-FABP on the prognosis of 28 days. RESULTS: Compared with the healthy volunteers, the serum D-lactate and I-FABP levels of ICU patients on day 0 were significantly increased [D-lactate (mg/L): 10.82 (3.31, 25.48) vs. 6.63 (1.54, 17.70), I-FABP (ng/L): 519.60 (159.06, 1 362.14) vs. 84.40 (30.78, 108.57), both P < 0.01], and D-lactate and I-FABP on day 5 were both decreased compared with the levels on day 0, but still higher than the healthy volunteers. I-FABP in the improvement group was significantly lower than that in the non-improvement group on day 0, and there was no significant difference in D-lactate levels between the two groups, D-lactate and I-FABP in both groups were significantly lower on day 5 than those on day 0, and D-lactate and I-FABP in the improvement group on day 5 were significantly lower than those in the non-improvement group [D-lactate (mg/L): 7.61 (1.71, 27.22) vs. 9.38 (2.09, 20.56), I-FABP (ng/L): 378.65 (152.56, 864.62) vs. 521.21 (205.93, 1 413.11), all P < 0.05]. Correlation analysis showed that D-lactate was significantly positively correlated with APACHE II score and SOFA score on day 0 and day 5 (R12 = 0.367, P < 0.001; R22 = 0.240, P = 0.012); I-FABP was significantly positively correlated with APACHE II score on day 0 (R2 = 0.264, P = 0.004); D-lactate on day 5 and I-FABP on day 0 and day 5 were significantly negatively correlated with prognosis on day 28 (R12 = -0.203, P = 0.022; R22 = -0.208, P = 0.023; R32 = -0.211, P = 0.021). The area under curve (AUC) analysis showed that D-lactate on day 5 and I-FABP on day 0 and day 5 had independent predictive value for 28-day prognosis, with AUC of 0.634, 0.638 and 0.652, P values of 0.023, 0.024 and 0.017, 95% confidence intervals (95%CI) of 0.533-0.734, 0.523-0.754 and 0.525-0.778, respectively. When the cut-off values were 7.71 mg/L, 593.55 ng/L and 468.10 ng/L, the sensitivity were 51.5%, 68.5% and 75.3%, and the specificity were 91.0%, 60.0% and 60.0%, respectively. CONCLUSIONS: Serum D-lactate and I-FABP were increased significantly and decreased with the improvement of the condition, and these two molecular biomarkers have certain value in predicting the prognosis of ICU patients.

[Dynamic changes in early gastric cantrum motility in craniocerebral injury patients].

OBJECTIVE: To investigate the dynamic changes in early gastric antrum contraction in patients with craniocerebral injury. METHODS: The patients with craniocerebral injury admitted to neurosurgery intensive care unit (ICU) of the First Affiliated Hospital of Sun Yat-sen University from July to November in 2018 were enrolled. The changes in antral contraction frequency (ACF), antral contraction amplitude (ACA) and antral motility index (MI) were dynamically observed at 1-6 days after injury by ultrasonography. According to Glasgow coma score (GCS), the patients were divided into moderate to severe craniocerebral (GCS ≤ 11) and mild craniocerebral injury groups (GCS > 11). The differences in ACF, ACA and MI between the two groups were compared to observe the effect of craniocerebral injury on gastric antral motility. The patients were divided into simple supratentorial and supratentorial combined infratentorial lesion groups according to the lesion location of craniocerebral injury. The differences in ACF, ACA and MI between the two groups were compared to analyze the influence of lesion location on gastric antrum activity. RESULTS: A total of 68 patients with craniocerebral injury were screened during the study period, 50 patients were in accorded with the admission criteria, 17 patients were withdrawn from the observation because they could not tolerate the ultrasonography of gastric antrum or discharged from ICU. Finally, 33 patients were enrolled in the analysis. (1) The ACF, ACA and MI at 1 day after injury were lower [ACF (times/min): 1.67 (0.00, 2.00), ACA: 42.06 (0.00, 44.45)%, MI: 0.70 (0.00, 0.87)], and then gradually increased, till 6 days after injury, ACF was 1.83 (1.25, 2.79) times/min, ACA was 56.80 (33.25, 60.77)%, and MI was 0.89 (0.50, 1.70), which showed no differences among all time points (all P > 0.05). (2) The contractile function of gastric antrum in two groups of patients with different degrees of craniocerebral injury was decreased, especially ACA in patients with moderate to severe craniocerebral injury (n = 22), which showed significant differences at 3 days and 5 days after injury as compared with mild craniocerebral injury [n = 11; 3 days: 35.05 (0.00, 53.69)% vs. 58.51 (49.90, 65.45)%, 5 days: 39.88 (0.00, 77.01)% vs. 56.94 (41.71, 66.66)%, both P < 0.05], indicating that the degree of craniocerebral injury affected the contractive function of gastric antrum. However, there was no significant difference in ACF or MI between the two groups at different time points after injury. (3) The contractile function of gastric antrum was decreased after craniocerebral injury in both groups of patients with different lesion locations of craniocerebral injury. The ACF, ACA, and MI at 3-4 days in patients with supratentorial combined infratentorial lesion (n = 12) were slightly lower than those in patients with simple supratentorial lesion [n = 21; 3 days: ACF (times/min) was 0.83 (0.00, 2.00) vs. 2.25 (0.00, 3.00), ACA was 35.05 (0.00, 53.60)% vs. 49.93 (0.00, 63.44)%, MI was 0.29 (0.00, 1.07) vs. 1.23 (0.00, 1.61); 4 days: ACF (times/min) was 1.42 (0.50, 2.63) vs. 2.00 (1.63, 2.63), ACA was 30.45 (21.69, 60.61)% vs. 43.29 (38.41, 53.35)%, MI was 0.50 (0.15, 1.45) vs. 0.97 (0.66, 1.28)] without statistical differences (all P > 0.05), indicating that the lesion location might not affect the contractive function of gastric antrum. CONCLUSIONS: In the early stage of craniocerebral injury, the contractile function of gastric antrum was decreased, and the more severe the craniocerebral injury, the worse contractive function of gastric antrum.

Boosting oxygen reduction activity with low-temperature derived high-loading atomic cobalt on nitrogen-doped graphene for efficient Zn-air batteries.

High-loading atomic cobalt (12.8 wt%) dispersed on nitrogen-doped graphene was successfully synthesized via considerably low temperature pyrolysis. The catalyst exhibits excellent electrocatalytic performance towards the oxygen reduction reaction with a large limiting diffusion current density of 5.60 mA cm-2 (10% higher than that of commercial Pt/C), and when acting as the air catalyst of Zn-air batteries, a high open-circuit voltage of >1.40 V and excellent power density are also achieved.

Altered expression of TIAM1 in endotoxin-challenged airway epithelial cells and rodent septic models.

BACKGROUND: In sepsis, reorganization of the actin cytoskeleton in the epithelium during inflammation will lead to a breakdown of epithelial barrier integrity, and contribute to the pathogenesis of sepsis, but the exact changes of various components regulating the actin cytoskeleton pathway remain unclear. METHODS: We used lipopolysaccharide (LPS) challenged primary epithelial cells cultured at the air-liquid interface (ALI) to mimic epithelial barrier dysfunction during sepsis. Then we detected differential expression of T-lymphoma invasion and metastasis 1 (TIAM1) gene in lung epithelial cells and septic models. RESULTS: LPS induced barrier dysfunction in human tracheobronchial epithelial cells (HTBEs) as measured by statistically significant changes in ionic and macromolecular permeability. We observed differential expression of TIAM1 gene. The protein expression of TIAM1 was decreased after LPS challenge, in human bronchial epithelial cells. Furthermore, the expression levels of both TIAM1 mRNA and protein were decreased in lungs of septic rodent models. CONCLUSIONS: Given that expression levels of TIAM1 have been associated with mortality among sepsis patients, our findings have the potential for the development of diagnostic and treatment strategies relevant for patient management.

Combined venomics, antivenomics and venom gland transcriptome analysis of the monocoled cobra (Naja kaouthia) from China.

We conducted an omics-analysis of the venom of Naja kaouthia from China. Proteomics analysis revealed six protein families [three-finger toxins (3-FTx), phospholipase A2 (PLA2), nerve growth factor, snake venom metalloproteinase (SVMP), cysteine-rich secretory protein and ohanin], and venom-gland transcriptomics analysis revealed 28 protein families from 79 unigenes. 3-FTx (56.5% in proteome/82.0% in transcriptome) and PLA2 (26.9%/13.6%) were identified as the most abundant families in venom proteome and venom-gland transcriptome. Furthermore, N. kaouthia venom expressed strong lethality (i.p. LD50: 0.79µg/g) and myotoxicity (CK: 5939U/l) in mice, and showed notable activity in PLA2 but weak activity in SVMP, l-amino acid oxidase or 5' nucleotidase. Antivenomic assessment revealed that several venom components (nearly 17.5% of total venom) from N. kaouthia could not be thoroughly immunocaptured by commercial Naja atra antivenom. ELISA analysis revealed that there was no difference in the cross-reaction between N. kaouthia and N. atra venoms against the N. atra antivenom. The use of commercial N. atra antivenom in treatment of snakebites caused by N. kaouthia is reasonable, but design of novel antivenom with the attention on enhancing the immune response of non-immunocaptured components should be encouraged. BIOLOGICAL SIGNIFICANCE: The venomics, antivenomics and venom-gland transcriptome of the monocoled cobra (Naja kaouthia) from China have been elucidated. Quantitative and qualitative differences are evident when venom proteomic and venom-gland transcriptomic profiles are compared. Two protein families (3-FTx and PLA2) are found to be the predominated components in N. kaouthia venom, and considered as the major players in functional role of venom. Other protein families with relatively low abundance appear to be minor in the functional significance. Antivenomics and ELISA evaluation reveal that the N. kaouthia venom can be effectively immunorecognized by commercial N. atra antivenom, but still a small number of venom components could not be thoroughly immunocaptured. The findings indicate that exploring the precise composition of snake venom should be executed by an integrated omics-approach, and elucidating the venom composition is helpful in understanding composition-function relationships and will facilitate the clinical application of antivenoms.

Fat-Modified Enteral Formula Improves Feeding Tolerance in Critically Ill Patients: A Multicenter, Single-Blind, Randomized Controlled Trial.

BACKGROUND: Improvement of fat digestion and absorption was supposed to relieve feeding intolerance. This trial aimed to evaluate the effect of a fat-modified enteral formula on feeding tolerance in critically ill patients. MATERIALS AND METHODS: This trial was conducted in 7 hospitals in China. In total, 144 intensive care unit (ICU) patients with estimated need of enteral nutrition (EN) for at least 5 days were randomly given fat-modified enteral formula containing medium-chain triglycerides (MCT), carnitine, and taurine (interventional feed group, n = 71) or standard enteral formula (control feed group, n = 73). EN intake, feeding intolerance (diarrhea, vomiting, gastric retention, and abdominal distension) and outcomes (mechanical ventilator-free days of 28 days, length of ICU stay, length of hospital stay, and in-hospital mortality) were collected. RESULTS: Daily calories and protein intake were increased in the interventional feed group compared with the control feed group ( P < .01). Total incidence of feeding intolerance was 42.3% in the interventional feed group and 65.7% in the control feed group ( P < .001). Daily incidence of feeding intolerance was 11.3%, 18.3%, 14.1%, 25.4%, and 26.1% in the interventional feed group and 31.5%, 32.9%, 34.2%, 34.2%, and 30.4% in the control feed group from study days 1-5 ( P = .0083). Incidence of feeding intolerance without abdominal distention was 32.9% in the interventional feed group and 49.3% in the control feed group ( P = .047), while the incidence of abdominal distension was 26.8% in the interventional feed group and 43.8% in the control feed group ( P = .03). No significant differences existed in outcomes between the 2 groups. CONCLUSIONS: The fat-modified enteral formula containing MCT, carnitine, and taurine may improve feeding tolerance in critically ill patients.

Inhibition of c-Jun N-terminal Kinase Signaling Pathway Alleviates Lipopolysaccharide-induced Acute Respiratory Distress Syndrome in Rats.

BACKGROUND: An acute respiratory distress syndrome (ARDS) is still one of the major challenges in critically ill patients. This study aimed to investigate the effect of inhibiting c-Jun N-terminal kinase (JNK) on ARDS in a lipopolysaccharide (LPS)-induced ARDS rat model. METHODS: Thirty-six rats were randomized into three groups: control, LPS, and LPS + JNK inhibitor. Rats were sacrificed 8 h after LPS treatment. The lung edema was observed by measuring the wet-to-dry weight (W/D) ratio of the lung. The severity of pulmonary inflammation was observed by measuring myeloperoxidase (MPO) activity of lung tissue. Moreover, the neutrophils in bronchoalveolar lavage fluid (BALF) were counted to observe the airway inflammation. In addition, lung collagen accumulation was quantified by Sircol Collagen Assay. At the same time, the pulmonary histologic examination was performed, and lung injury score was achieved in all three groups. RESULTS: MPO activity in lung tissue was found increased in rats treated with LPS comparing with that in control (1.26 ± 0.15 U in LPS vs. 0.77 ± 0.27 U in control, P < 0.05). Inhibiting JNK attenuated LPS-induced MPO activity upregulation (0.52 ± 0.12 U in LPS + JNK inhibitor vs. 1.26 ± 0.15 U in LPS, P < 0.05). Neutrophils in BALF were also found to be increased with LPS treatment, and inhibiting JNK attenuated LPS-induced neutrophils increase in BALF (255.0 ± 164.4 in LPS vs. 53 (44.5-103) in control vs. 127.0 ± 44.3 in LPS + JNK inhibitor, P < 0.05). At the same time, the lung injury score showed a reduction in LPS + JNK inhibitor group comparing with that in LPS group (13.42 ± 4.82 vs. 7.00 ± 1.83, P = 0.001). However, the lung W/D ratio and the collagen in BALF did not show any differences between LPS and LPS + JNK inhibitor group. CONCLUSIONS: Inhibiting JNK alleviated LPS-induced acute lung inflammation and had no effects on pulmonary edema and fibrosis. JNK inhibitor might be a potential therapeutic medication in ARDS, in the context of reducing lung inflammatory.

N-Acetylcysteine Inhibits Ventilation-Induced Collagen Accumulation in the Rat Lung.

Mechanical ventilation is the most important life supportive therapy for patients with acute respiratory distress syndrome (ARDS). However, increasing evidence from clinical studies suggests that mechanical ventilation can cause lung fibrosis, which may significantly contribute to morbidity and mortality. Recent studies also found fibroproliferation occurred in early stage of ARDS with poor outcome. We have hypothesized that mechanical ventilation-induced lung injury may be a major contributor to lung fibrosis, and antioxidant could be a potential therapeutic agent for the treatment to mechanic ventilation induced fibroproliferation. We therefore used Sprague-Dawley rats that were ventilated with large tidal volume (20 ml/kg) or low tidal volume (7 ml/kg). We analyzed the time course of collagen level in the lung and the effect of N-acetylcysteine (NAC), a thiol antioxidant, on mechanical ventilation-induced collagen accumulation. In addition, normal human lung fibroblasts (NHLF) were exposed to mechanical stretch, which mimics ventilator-induced lung inflation, to evaluate the collagen secretion in culture medium. We found that ventilation-induced collagen accumulation occurred even after 2-hour ventilation. Pretreatment with NAC (140 mg/kg) inhibited collagen accumulation in lungs of rats ventilated with large tidal volume. Moreover, mechanical stretch caused the accumulation of collagen in the culture medium of NHLF, the magnitude of which was decreased with the pretreatment with NAC (1 mM). These results indicate that mechanical ventilation can induce collagen accumulation within 2 hours. NAC alleviated the collagen accumulation induced by mechanical ventilation with high tidal volume. Therefore, NAC can be considered as a good candidate in preventing ventilation-induced lung fibrosis.