Crushing Response and Optimization of a Modified 3D Re-Entrant Honeycomb.

A modified 3D re-entrant honeycomb is designed and fabricated utilizing Laser Cladding Deposition (LCD) technology, the mechanical properties of which are systematically investigated by experimental and finite element (FE) methods. Firstly, the influences of honeycomb angle on localized deformation and the response of force are studied by an experiment. Experimental results reveal that the honeycomb angles have a significant effect on deformation and force. Secondly, a series of numerical studies are conducted to analyze stress characteristics and energy absorption under different angles (α) and velocities (v). It is evident that two variables play an important role in stress and energy. Thirdly, response surface methodology (RSM) and the Non-Dominated Sorting Genetic Algorithm II (NSGA-II) are implemented with high precision to solve multi-objective optimization. Finally, the final compromise solution is determined based on the fitness function, with an angle of 49.23° and an impact velocity of 16.40 m/s. Through simulation verification, the errors of energy absorption (EA) and peak crush stress (PCS) are 9.26% and 0.4%, respectively. The findings of this study offer valuable design guidance for selecting the optimal design parameters under the same mass conditions to effectively enhance the performance of the honeycomb.

Safety and effcacy of remimazolam tosilate for sedation during combined spinal-epidural anesthesia for orthopedic procedures: a randomized controlled trial.

OBJECTIVE: The objective of this study was to assess the efficacy and safety of Remimazolam in the context of combined spinal-epidural anesthesia for sedation during orthopedic surgery. METHODS: This randomized controlled trial enrolled patients scheduled for orthopedic surgery under combined spinal-epidural anesthesia (N = 80), who were randomly allocated to receive either dexmedetomidine (Group-D) or remimazolam (Group-R). The target sedation range aimed for a Ramsay score of 2-5 or a BIS value of 60-80 to evaluate the effectiveness and safety of remimazolam during sedation. RESULTS: The time taken to achieve the desired level of sedation was significantly shorter in the remimazolam group compared to the dexmedetomidine group (3.69 ± 0.75 vs. 9.59 ± 1.03; P < 0.0001). Patients in the remimazolam group exhibited quicker recovery, fewer intraoperative adverse events, more consistent vital signs, and greater satisfaction at various time points throughout the surgery. CONCLUSION: This preliminary study demonstrates that remimazolam tosilate serves as a safe and effective sedative for orthopedic surgery performed under combined spinal-epidural anesthesia, in comparison with dexmedetomidine.

Emergence of a clinical isolate of E. coil ST297 co-carrying blaNDM-13 and mcr-1.1 in China.

BACKGROUND: The coexistence of carbapenem resistance genes and mcr-1.1 in Enterobacterales has been an urgent and persistent threat to global public health. In this study, we isolated a clinical NB4833, an Escherichia coli isolate that co-carries mcr-1.1 and blaNDM-13. OBJECTIVES: This study aimed to isolate a clinical NB4833, an Escherichia coli isolate that co-carries mcr-1.1 and blaNDM-13 and investigated the phenotypic and genotypic characteristics of plasmids harbored by E. coli isolate NB4833. METHODS: Antimicrobial susceptibility testing and conjugation assay were performed on E. coli isolate NB4833. Stability of the plasmid and growth rate determination were used to characterize the plasmids harboring mcr-1.1 and blaNDM-13. In addition, the genetic characteristics of the plasmids were analyzed based on whole-genome sequencing of the strain and comparative genetic analysis with related plasmids. RESULTS: Whole-genome sequencing showed that the isolate carried multiple resistance genes and possessed phenotypes indicative of all antibiotic resistance except tigecycline. And the mcr-1.1- and blaNDM-13-harbouring plasmids showed relatively high similarity to the related plasmids. The pNB4833-NDM-13 plasmid was capable of trans conjugation with an efficiency of 1.04 × 10-2 in a filter mating experiment and the transconjugant J53/ pNB4833-NDM-13 was able to be stably inherited after 10 days of passage. CONCLUSIONS: To our knowledge, this is the first report of the coexistence of the IncI2 plasmid carrying mcr-1.1 and a blaNDM-13-carrying integrated IncFIB/IncFII plasmid in an ST297 clinical E. coli isolate. In addition, we investigated a novel plasmid carrying blaNDM-13. Our study expands the diversity of plasmids carrying blaNDM-13, which exhibits epidemic importance in bacterial resistance. Therefore, there are important measures that should be taken to prevent the spread of these plasmids.

Development and Initial Validation of the Positive and Negative Co-Rumination Scale.

This article presents two studies with data from 750 college students (58.67% females, Mage = 20.79 years) and 1035 school students (52.1% girls, Mage = 14.44 years) respectively, describing the development and initial validation of the Positive and Negative Co-Rumination Scale (PANCRS). The PANCRS consists of 32 items with 3 second-order factors: Positive Co-Rumination consisting of 3 first-order factors (i.e., Affirmation, Problem-Solving and Enhancing Friendship), Negative Co-Rumination consisting of 4 first-order factors (i.e., Worry About Evaluation, Inhibiting Happiness, Worry About Impact and Slack) and Frequency consisting of 2 first-order factors (i.e., Frequencies of Co-Rumination on Positive and Negative Events). Results from exploratory and confirmatory factor analyses confirmed the measure's 9 first-order and 3 second-order factors structure. Moreover, correlation analyses provided first evidence for the subscales' differential validity: (1) Positive Co-Rumination showed positive correlations with positive indicators of psychological adjustment (i.e., friendship quality and life satisfaction) and negative correlations with negative indicators of psychological adjustment (i.e., anxiety and depression); (2) Negative Co-Rumination showed non-significant or negative correlations with positive indicators of psychological adjustment and positive correlations with negative indicators of psychological adjustment; (3) Frequency showed positive correlations with both positive and negative indicators of psychological adjustment. In addition, all PANCRS scores showed satisfactory composite reliability (omegas) and temporal stability (test-retest). Overall the findings suggest that the PANCRS is a reliable and valid instrument to assess positive and negative aspects of Co-rumination.

Comparison of different therapeutic approaches for pulmonary cryptococcosis in kidney transplant recipients: a 15-year retrospective analysis.

Introduction: Organ transplant recipients are at increased risk of developing pulmonary cryptococcosis (PC) due to weakened cell-mediated immunity caused by immunosuppressors. However, the nonspecific symptoms associated with PC can often lead to misdiagnosis and inappropriate treatment. Methods: We conducted a retrospective analysis of data from 23 kidney transplant recipients with PC between April 2006 to January 2021. Results: The median time from transplantation to the diagnosis of pathology-proven PC 4.09 years. Seventeen patients presented respiratory symptoms, including sputum-producing cough and dyspnea. Additionally, three patients also developed central nervous system (CNS) infections. Chest CT scans frequently revealed nodule-shaped lesions, which can mimic lung carcinoma. Serological tests did not demonstrate any specific changes. Nine patients received surgical resection as treatment. Fourteen patients were treated with antifungal medication only. No recurrence was observed in all 23 patients. Conclusion: Our study suggests that fever and sputum-producing cough are common symptoms of PC, and cryptococcal meningitis should not be excluded if corresponding symptoms occur. Fluconazole is a common and effective antifungal agent. Surgical resection should be considered for patients who do not respond well to antifungal therapy. Clinicians should be aware of these findings when evaluating transplant recipients with respiratory symptoms.

Transcriptomic analyses reveal the potential antibacterial mechanism of citral against Staphylococcus aureus.

Background: The emergence of multi-drug resistant Staphylococcus aureus (S. aureus) has posed a challenging clinical problem for treating its infection. The development of novel or new antibacterial agents becomes one of the useful methods to solve this problem, and has received more attention over the past decade. Citral is reported to have antibacterial activity against S. aureus, but its mechanism is yet entirely clear. Methods: To reveal the antibacterial mechanism of citral against S. aureus, comparative transcriptomic analysis was carried out to analyze the gene expression differences between the citral-treated and untreated groups. The changes of protein, adenosine triphosphate (ATP) and reactive oxygen species (ROS) content in S. aureus caused by citral were also examined. Results: Six hundred and fifty-nine differentially expressed genes were obtained according to the comparative transcriptomic analysis, including 287 up-regulated genes and 372 down-regulated genes. The oxidoreductase activity and fatty acid degradation pathway were enriched in up-regulated genes, and ribosome and S. aureus infection pathway were enriched in down-regulated genes. Meanwhile, physiological trials revealed a decline in ATP and protein levels, but an increase in ROS content within the citral-treated group. Thus, it can be inferred that the antibacterial effects of citral against S. aureus were likely due to its ability to decrease ATP content by down-regulating ATP synthase genes (atpD and atpG), reduce protein content, induce cell membrane and cell wall damages, accumulate ROS, and down-regulate virulence factor genes to reduce pathogenicity. Conclusion: These findings revealed the antibacterial mechanism of citral was likely a type of multi-target mode that affected multiple molecular processes in S. aureus, which lays the groundwork for further exploitation of citral as a therapeutic candidate against S. aureus infections.

Life cycle cost analysis of solar energy via environmental externality monetization.

Evaluating the embodied environmental impact of solar photovoltaic (PV) technology has been an important topic in addressing the sustainable development of renewable energy. While monetization of environmental externality is a remaining issue, which should be carried out in order to allow for an easy-to-understand comparison between direct economic and external cost. In this study, the environmental impact of solar PV power is monetized through conversion factors between midpoint and endpoint categories of life cycle analysis and the monetization weighting factor. Then, the power generation capacity and generation life of PV and coal-fired power plants are assumed to be consistent in order to compare the total cost of PV and coal-fired power generation. Results show that the cost of PV technology is higher than coal-fired form the base year from 2026 until 2030, taking into account environmental external costs and production costs. However, by 2030, the total cost of coal-fired power will be higher than that of solar PV. The life span cost per kWh is $3.55 for solar PV and $116.25 for coal-fired power. Although solar PV power seems more environmentally effective than coal-fired power in the life span, our results reveal the high environmental external cost of producing solar photovoltaic modules, which reminds us to pay more attention to the environmental impact when conducting cost-benefit analysis of renewable technologies. Without incorporating the environmental cost, the real cost of renewable technology will be underestimated.

Potentially Toxic Element Contaminations and Lead Isotopic Fingerprinting in Soils and Sediments from a Historical Gold Mining Site.

Lead (Pb) isotopes have been widely used to identify and quantify Pb contamination in the environment. Here, the Pb isotopes, as well as the current contamination levels of Cu, Pb, Zn, Cr, Ni, Cd, As, and Hg, were investigated in soil and sediment from the historical gold mining area upstream of Miyun Reservoir, Beijing, China. The sediment had higher 206Pb/207Pb ratios (1.137 ± 0.0111) than unpolluted soil did (1.167 ± 0.0029), while the soil samples inside the mining area were much more variable (1.121 ± 0.0175). The mean concentrations (soil/sediment in mg·kg-1) of Pb (2470/42.5), Zn (181/113), Cu (199/36.7), Cr (117/68.8), Ni (40.4/28.9), Cd (0.791/0.336), As (8.52/5.10), and Hg (0.168/0.000343) characterized the soil/sediment of the studied area with mean Igeo values of the potentially toxic element (PTE) ranging from -4.71 to 9.59 for soil and from -3.39 to 2.43 for sediment. Meanwhile, principal component analysis (PCA) and hierarchical cluster analysis (HCA) coupled with Pearson's correlation coefficient among PTEs indicated that the major source of the Cu, Zn, Pb, and Cd contamination was likely the mining activities. Evidence from Pb isotopic fingerprinting and a binary mixing model further confirmed that Pb contamination in soil and sediment came from mixed sources that are dominated by mining activity. These results highlight the persistence of PTE contamination in the historical mining site and the usefulness of Pb isotopes combined with multivariate statistical analysis to quantify contamination from mining activities.

Comparative transcriptome analysis reveals gene expression differences between two peach cultivars under saline-alkaline stress.

BACKGROUND: Saline-alkaline stress is a major abiotic stress that is harmful to plant growth worldwide. Two peach cultivars (GF677 and Maotao) display distinct phenotypes under saline-alkaline stress. The molecular mechanism explaining the differences between the two cultivars is still unclear. RESULTS: In the present study, we systematically analysed the changes in GF677 and Maotao leaves upon saline-alkaline stress by using cytological and biochemical technologies as well as comparative transcriptome analysis. Transmission electron microscopy (TEM) observations showed that the structure of granum was dispersive in Maotao chloroplasts. The biochemical analysis revealed that POD activity and the contents of chlorophyll a and chlorophyll b, as well as iron, were notably decreased in Maotao. Comparative transcriptome analysis detected 881 genes with differential expression (including 294 upregulated and 587 downregulated) under the criteria of |log2 Ratio| ≥ 1 and FDR ≤0.01. Gene ontology (GO) analysis showed that all differentially expressed genes (DEGs) were grouped into 30 groups. MapMan annotation of DEGs showed that photosynthesis, antioxidation, ion metabolism, and WRKY TF were activated in GF677, while cell wall degradation, secondary metabolism, starch degradation, MYB TF, and bHLH TF were activated in Maotao. Several iron and stress-related TFs (ppa024966m, ppa010295m, ppa0271826m, ppa002645m, ppa010846m, ppa009439m, ppa008846m, and ppa007708m) were further discussed from a functional perspective based on the phylogenetic tree integration of other species homologues. CONCLUSIONS: According to the cytological and molecular differences between the two cultivars, we suggest that the integrity of chloroplast structure and the activation of photosynthesis as well as stress-related genes are crucial for saline-alkaline resistance in GF677. The results presented in this report provide a theoretical basis for cloning saline-alkaline tolerance genes and molecular breeding to improve saline-alkaline tolerance in peach.

The application of metagenomic next-generation sequencing in diagnosing Chlamydia psittaci pneumonia: a report of five cases.

BACKGROUND: Chlamydia psittaci pneumonia is a zoonotic infectious disease caused by Chlamydia psittaci. Diagnostic tools, including culture, serologic test and PCR-based methods, are available but prone to false negative results. CASE PRESENTATION: This report included five cases of Chlamydia psittaci pneumonia. Symptoms and signs common to all 5 cases included fever, coughing, generalized muscle ache, and most notably, inflammatory infiltration of the lungs upon chest CT and X-ray. Metagenomic next-generation sequencing (mNGS) revealed the presence of Chlamydia psittaci in biopsy lung tissue in 3 cases and bronchoalveolar lavage fluid in the remaining 2 cases. Three patients responded to doxycycline plus moxifloxacin; two patients responded to moxifloxacin alone. CONCLUSIONS: mNGS could be used to diagnose Chlamydia psittaci pneumonia.

Silencing FUNDC1 alleviates chronic obstructive pulmonary disease by inhibiting mitochondrial autophagy and bronchial epithelium cell apoptosis under hypoxic environment.

Chronic obstructive pulmonary disease (COPD) is a major global epidemic with increasing incidence worldwide. The pathogenesis of COPD is involved with mitochondrial autophagy. Recently, it has been reported that FUN14 domain containing 1 (FUNDC1) is a mediator of mitochondrial autophagy. Therefore, we hypothesized that FUNDC1 was involved in cigarette smoke (CS)-induced COPD progression by regulating mitochondrial autophagy. In vitro cigarette smoke extract (CSE)-treated human bronchial epithelial cell (hBEC) Beas-2B cell line and in vivo CS-induced COPD mouse models were developed, in which FUNDC1 expression was measured. Next, whether FUNDC1 interacted with dynamin-related protein 1 (DRP1) in COPD was investigated. The functional mechanism of FUNDC1 in COPD was evaluated through gain- or loss-of-function studies. Then, pulmonary function, mitochondrial transmembrane potential (MTP) and mucociliary clearance (MCC) were examined. Levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) and expression of autophagy-specific markers (light chain 3 [LC3] II, LC3 I, and Tom20) were measured. Finally, apoptosis and mitochondrial autophagy were assessed. FUNDC1 was highly expressed in CSE-treated hBECs and COPD mice. Meanwhile, FUNDC1 was proved to interact with DRP1 in CSE-treated cells. Moreover, in CSE-treated hBECs, silencing FUNDC1 was observed to reduce levels of IL-6 and TNF-α, and MTP but increase MCC, and inhibit CSE-induced mitochondrial autophagy and Beas-2B cell apoptosis, which was consistent with the trend in COPD mouse models. In addition, pulmonary function of COPD mouse models was increased in response to FUNDC1 silencing. Finally, silencing of DRP1 also inhibited mitochondrial autophagy and Beas-2B cell apoptosis. Collectively, FUNDC1 silencing could suppress the progression of COPD by inhibiting mitochondrial autophagy and hBEC apoptosis through interaction with DRP1, highlighting a potential therapeutic target for COPD treatment.

Discovery of a Thiadiazole-Pyridazine-Based Allosteric Glutaminase 1 Inhibitor Series That Demonstrates Oral Bioavailability and Activity in Tumor Xenograft Models.

Tumors have evolved a variety of methods to reprogram conventional metabolic pathways to favor their own nutritional needs, including glutaminolysis, the first step of which is the hydrolysis of glutamine to glutamate by the amidohydrolase glutaminase 1 (GLS1). A GLS1 inhibitor could potentially target certain cancers by blocking the tumor cell's ability to produce glutamine-derived nutrients. Starting from the known GLS1 inhibitor bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide, we describe the medicinal chemistry evolution of a series from lipophilic inhibitors with suboptimal physicochemical and pharmacokinetic properties to cell potent examples with reduced molecular weight and lipophilicity, leading to compounds with greatly improved oral exposure that demonstrate in vivo target engagement accompanied by activity in relevant disease models.

Antitumor activity and underlying mechanism of Sargassum fusiforme polysaccharides in CNE-bearing mice.

This study was designed to investigate the antitumor effects of Sargassum fusiforme polysaccharides (SFPS) on nasopharyngeal carcinoma (NPC) and the underlying mechanism of its effect on splenic lymphocytes. As a result, SFPS significantly inhibited the growth of nasopharyngeal carcinoma CNE in vivo, and remarkably increased the serum cytokines and IgM levels in CNE-bearing mice. Meanwhile, SFPS stimulated the peritoneal macrophages to secrete the cytokines, exerted a stimulatory effect on splenic lymphocytes proliferation, and increased the expression of IgM from splenic lymphocytes. The pretreatment of splenic lymphocytes with special antibodies (anti-TLR4 and anti-TLR2) significantly suppressed the proliferation of splenic lymphocytes and blocked SFPS-induced IgM production. SB203580, a specific inhibitor of p38 MAPK, effectively suppressed SFPS-induced IgM secretion in splenic lymphocytes. Taken together, SFPS has antitumor and immunomodulatory activities in NPC, and its activity is mediated, at least in part, by TLR2/TLR4 receptors and p38 MAPK signaling pathway.

Ginkgolide B Suppresses Methamphetamine-Induced Microglial Activation Through TLR4-NF-κB Signaling Pathway in BV2 Cells.

Accumulating evidence suggests that microglial cells have altered morphology and proliferation in different brain regions of methamphetamine (Meth) abusers and Meth-abusing animal models. However, the possible mechanisms underlying Meth-induced microglial activation remain poorly understood. Meanwhile, Toll-like receptor4 (TLR4) is closely associated with inflammation. Therefore the aim of the present study was to assess whether Meth treatment affects TLR4 expression; in addition, we evaluated the effects of ginkgolide B (GB), a diterpene lactone extracted from Ginkgo biloba, on Meth-mediated inflammation. BV2 cells were treated with Meth. Interestingly, Meth treatment significantly increased TLR4 expression, activated the NF-κB signaling pathway, and promoted TNF-α, IL-6 and IL-1ß excretion. These effects, however, were partially attenuated by GB pre-treatment. To further confirm the role of TLR4 in Meth-mediated inflammation, the siRNA technology was applied to knock down TLR4, which resulted in hampered Meth-mediated inflammatory responses, confirming the important role of TLR4 in this process. Taken together, our findings suggested that Meth exposure results in BV2 cell activation, in association with TLR4 upregulation. GB could attenuate Meth-induced inflammation, at least partially through TLR4-NF-κB signaling pathway, therefore, targeting TLR4 may constitute a potential intervention strategy for Meth mediated neuroinflammation.

HBV-Associated Postinfectious Acute Glomerulonephritis: A Report of 10 Cases.

Postinfectious acute glomerulonephritis (PIGN) may occur after various bacterial and viral infections. Hepatitis B virus (HBV) infection is a cause of chronic glomerulonephritis. We report here 10 cases (ages 7-20 years-old) of chronic HBV carriers with acute glomerulonephritis, with positive glomerular staining of hepatitis B surface antigen, and detectable presence of HBV DNA in the glomeruli. This form of PIGN, HBV-PIGN, has not been previously identified. To further characterize clinical and pathological features of HBV- PIGN, we selected 10 cases of age-matched non-HBV PIGN for comparison. While both HBV associated PIGN and non-HBV PIGN similarly presented as proteinuria, hematuria, and hypertension, there was a trend of higher acute kidney injury and worsened prognosis in HBV-PIGN. 6 months after the onset, 4 patients with HBV associated PIGN did not show improvement from the disease, whereas all patients with non-HBV PIGN had complete or partial recovery. Pathologically, both HBV associated PIGN and non-HBV PIGN showed typical diffuse glomerular endocapillary proliferation, but HBV associated PIGN differed from classical PIGN with much fewer sub-epithelial glomerular "hump-shape" immune complex depositions. In conclusion, we have identified a novel association of HBV infection with acute glomerulonephritis.

Comparison of Laparoscopic Appendectomy with open appendectomy in Treating Children with Appendicitis.

OBJECTIVE: To analyze feasibility and curative effect of laparoscopic appendectomy in the treatment of pediatric appendicitis and compare it with open appendectomy. METHODS: Two hundred and sixty patients were selected for this study and randomly divided into open appendectomy group (130 cases) and laparoscopic appendectomy group (130 cases). Patients in open appendectomy group underwent traditional open appendectomy, while patients in laparoscopic appendectomy were treated with laparoscopic appendectomy. Incision length, blood loss during operation, duration of operation, time to leave bed, anus exhausting time, time to take food, catheter drainage time, urinary catheterization time, time of using antibiotics, use of pain killer and incidence of complications such as incision infection, residual abscess and intestinal obstruction were compared between two groups. RESULTS: We found relevant indexes including length of incision, amount of bleeding and duration of operation in laparoscopic appendectomy group were better than open appendectomy group after surgery; and differences were statistically significant (P<0.05). Indexes such as time to out of bed, time to take food, exhaust time, drainage time, catheterization time and application time and use of antibiotics in laparoscopic appendectomy group were all superior to open appendectomy group, and differences had statistical significance (P<0.05). Incidence of complications in laparoscopic appendectomy group was much lower than open appendectomy group and the difference was statistically significant (P<0.05). CONCLUSION: Laparoscopic appendectomy has advantages of small trauma, sound curative effect, low incidence of complications and rapid recovery and can effectively relieve pain of children suffering from appendicitis. Hence it is worth promotion and should be preferred.

Continuous venovenous hemofiltration decreases mortality and ameliorates acute lung injury in canine model of severe salt water drowning.

BACKGROUND: Pulmonary edema is an important cause of complications and death in severe drowning. Continuous veno-venous hemofiltration (CVVH) may reduce pulmonary edema and thus may be a treatment modality for severe sea water drowning resuscitation. METHOS: 20 dogs were anesthetized and tracheally intubated. 10 ml/kg of sea water was infused into trachea in a minute. All animals developed signs of respiratory distress and severe hypoxia (PaO2 < 40 mmHg) within 15 minutes after infusion. They were then mechanical ventilated and randomized to receive either CVVH (n = 10) or no additional treatment (control, n = 10) and followed over 4 hours. Arterial gas, hemodynamic parameters, and the levels of circulating inflammatory cytokines including interleukin 6 (IL-6), interleukin 8 (IL-8), and tumor necrosis factor α (TNFα) were determined. Additionally, blood endothelin and the levels of oxidative stress in lung were measured at sacrifice. RESULTS: 5 animals in the control group (50%) died within 4 hours after sea water aspiration, while 10 animals received CVVH all survived (p < 0.05). Importantly, CVVH significantly improved blood gas exchange as evidenced by higher PaO2, normal oxygen saturation, and no carbon dioxide retention after 3 hour of CVVH, while also correcting against acidosis. Levels of circulating IL-6, IL-8, and TNFα were elevated in control but not in CVVH group (p < 0.01). CVVH also reduced plasma endothelin and alleviated oxidative stress. Histology examination further revealed reductions in pulmonary alveolar injury, blood congestion, and inflammation by CVVH. DISCUSSION AND CONCLUSIONS: CVVH decreased mortality and pulmonary injury and largely maintained hemodynamic and acid-base balance in animals with severe sea water drowning and thus, may be added as a new measure to aid in resuscitation from severe sea water drowning. TRIAL REGISTRATION: Animal protocol number: FZG0001859 http://www.fzzyy.com.

Influence of interleukin-28B polymorphism on progression to hepatitis virus-induced hepatocellular carcinoma.

Genetic variation of interleukin-28B (IL-28B) rs12979860 T/C polymorphism is associated with the immune response to interferon (IFN) therapy, which is applied in the treatment of chronic viral hepatitis induced by hepatitis B virus (HBV) and hepatitis C virus (HCV). These chronic liver diseases could progress to end-stage liver diseases, such as hepatocellular carcinoma (HCC). The aim of this study was to clarify whether there exists a causal association between IL-28B rs12979860 T/C polymorphism and development of HCC. In a meta-analysis of six studies with 850 cases and 811 controls, we summarized the data on the association between IL-28B rs12979860 T/C polymorphism and HCC risk and calculated ORs and 95 % CIs to estimate the association strength. We observed that IL-28B rs12979860 T/C polymorphism was positively associated with overall HCC risk (TT vs. CC: OR = 2.38; 95 %, 1.60-3.55; TT vs CT + CC: OR = 1.79; 95 %, 1.23-2.60). In the stratified analysis by ethnicity, the robust association retained in Caucasians with higher risk among TT carriers relative to the CC carriers. A similar trend was found in the studies of healthy controls when data were stratified by source of controls. The combined data suggest that IL-28B rs12979860 T/C polymorphism seems to augment the risk of developing HCC, especially in Caucasians.

Sargassum fusiforme polysaccharide activates nuclear factor kappa-B (NF-κB) and induces cytokine production via Toll-like receptors.

This study was designed to investigate the mechanism of macrophage activation by the Sargassum fusiforme polysaccharide (SFPS). As a result, SFPS significantly enhanced cytokines and nitric oxide (NO) productions in peritoneal macrophages, and stimulated macrophages to produce the cytokines and NO through the induction of their genes expression. The pretreatment of peritoneal macrophages with special antibodies [Toll-like receptors (TLRs) antibody] significantly blocked SFPS-induced tumor necrosis factor alpha (TNF-α) and NO production. Furthermore, pyrrolidine dithiocarbamate (PDTC), a specific inhibitor of NF-κB, effectively suppressed SFPS-induced TNF-α and interleukin 1ß (IL-1ß) secretion in peritoneal macrophages, indicating that SFPS stimulated macrophages to produce cytokines through the NF-κB pathway and the result was further confirmed by the experiment of Western blotting (WB) and confocal laser scanning microscope (CLSM). Taken together, these results suggest that SFPS-mediated induction of cytokines and NO production in macrophages is mediated, at least in part, by TLRs/NF-κB signaling pathway.