GTS-21 attenuates ACE/ACE2 ratio and glycocalyx shedding in lipopolysaccharide-induced acute lung injury by targeting macrophage polarization derived ADAM-17.

Acute lung injury (ALI) has received considerable attention in intensive care owing to its high mortality rate. It has been demonstrated that the selective alpha7 nicotinic acetylcholine receptor agonist Gainesville Tokushima scientists (GTS)-21 is promising for treating ALI caused by lipopolysaccharides (LPS). However, the precise underlying mechanism remains unknown. This study aimed to investigate the potential efficacy of GTS-21 in the treatment of ALI. We developed mouse models of ALI and alveolar epithelial type II cells (AT2s) injury following treatment with LPS and different polarized macrophage supernatants, respectively. Pathological changes, pulmonary edema, and lung compliance were assessed. Inflammatory cells count, protein content, and pro-inflammatory cytokine levels were analysed in the bronchoalveolar lavage fluid. The expression of angiotensin-converting enzyme (ACE), ACE2, syndecan-1 (SDC-1), heparan sulphate (HS), heparanase (HPA), exostosin (EXT)-1, and NF-κB were tested in lung tissues and cells. GTS-21-induced changes in macrophage polarization were verified in vivo and in vitro. Polarized macrophage supernatants with or without recombination a disintegrin and metalloproteinase-17 (ADAM-17) and small interfering (si)RNA ADAM-17 were used to verify the role of ADAM-17 in AT2 injury. By reducing pathological alterations, lung permeability, inflammatory response, ACE/ACE2 ratio, and glycocalyx shedding, as well as by downregulating the HPA and NF-κB pathways and upregulating EXT1 expression in vivo, GTS-21 significantly diminished LPS-induced ALI compared to that of the LPS group. GTS-21 significantly attenuated macrophage M1 polarization and augmented M2 polarization in vitro and in vivo. The destructive effects of M1 polarization supernatant can be inhibited by GTS-21 and siRNA ADAM-17. GTS-21 exerted a protective effect against LPS-induced ALI, which was reversed by recombinant ADAM-17. Collectively, GTS-21 alleviates LPS-induced ALI by attenuating AT2s ACE/ACE2 ratio and glycocalyx shedding through the inhibition of macrophage M1 polarization derived ADAM-17.

Unraveling EGFR-TKI resistance in lung cancer with high PD-L1 or TMB in EGFR-sensitive mutations.

BACKGROUND: Although EGFR-TKI resistance mechanisms in non-small cell lung cancer (NSCLC) have been extensively studied, certain patient subgroups remain with unclear mechanisms. This retrospective study analysed mutation data of NSCLC patients with EGFR-sensitive mutations and high programmed death-ligand 1 (PD-L1) expression or high TMB to identify primary resistance mechanisms. METHODS: Hybrid capture-based next-generation sequencing (NGS) was used to analyse mutations in 639 genes in tumor tissues and blood samples from 339 NSCLC patients. PD-L1 immunohistochemical staining was also performed on the same cell blocks. Molecular and pathway profiles were compared among patient subgroups. RESULTS: TMB was significantly higher in lung cancer patients with EGFR-sensitive mutations and high PD-L1 expression. Compared with the high-expression PD-L1 or high TMB and low-expression or TMB groups, the top 10 genes exhibited differences in both gene types and mutation rates. Pathway analysis revealed a significant mutations of the PI3K signaling pathway in the EGFR-sensitive mutation group with high PD-L1 expression (38% versus 12%, p < 0.001) and high TMB group (31% versus 13%, p < 0.05). Notably, PIK3CA and PTEN mutations emerged as the most important differentially mutated genes within the PI3K signaling pathway. CONCLUSIONS: Our findings reveal that the presence of PI3K signaling pathway mutations may be responsible for inducing primary resistance to EGFR-TKIs in NSCLC patients with EGFR-sensitive mutations along with high PD-L1 expression or high TMB. This finding is of great significance in guiding subsequent precision treatments in NSCLC.

Clinical utility of keratin 14 expression measurement in reflecting the tumor properties and prognosis in patients with renal cell carcinoma: a study with long-term follow-up.

PURPOSE: Keratin 14 (KRT14) is hypothesized to be involved in the pathogenesis of renal cell carcinoma (RCC) based on its tumorigenic role in various cancers and its relationship with the prognosis of other urinary system malignancies. This study aimed to evaluate the correlation of KRT14 with tumor properties and prognosis in RCC patients. METHODS: Data from 180 RCC patients who received tumor resection were retrospectively reviewed. The KRT14 was assessed by immunohistochemistry (IHC) staining in tumor tissues and non-tumor tissues. RESULTS: KRT14 was insufficiently expressed in both tumor and non-tumor tissues, with median (interquartile range) IHC score of 2.0 (0.0-3.4) and 1.0 (0.0-2.0), respectively. While it was relatively higher in tumor versus non-tumor tissues (P < 0.001). Besides, tumor KRT14 was positively correlated with the pathological grade (P = 0.038), tumor size (P = 0.012), T stage (P = 0.006), and TNM stage (P = 0.018). Interestingly, tumor KRT14 high predicted shorter accumulating recurrence-free survival (RFS) (P = 0.003) and accumulating overall survival (OS) (P = 0.001), which was further verified by the multivariate Cox's regression analysis (both P < 0.05). Furthermore, tumor KRT14 high estimated shorter RFS and OS from the Gene Expression Profiling Interactive Analysis and Human Protein ATLAS databases (all P < 0.05). Subgroup analyses indicated that the correlation of tumor KRT14 with accumulating RFS and accumulating OS was more pronounced in RCC patients with better physical status (such as age < 65 years and better eastern cooperative oncology group performance status) and higher tumor stages (such as higher pathological grade). CONCLUSION: High KRT14 in tumor tissue could reflect an advanced tumor features and unsatisfying survival in RCC patients.

Environmental cadmium pollution and health risk assessment in rice-wheat rotation area around a smelter.

Cadmium (Cd) pollution induced by smelting process is of great concern worldwide. However, the comprehensive risk assessment of Cd exposures in smelting areas with farming coexist is lacking. In this study, atmospheric deposition, soil, surface and drinking water, rice, wheat, vegetable, fish, pork, and human hair samples were collected in rice-wheat rotation area near nonferrous smelter to investigate smelting effect on environmental Cd pollution and human health. Results showed high Cd deposition (0.88-2.61 mg m-2 year-1) combined with high bioavailability (37-42% totality) in study area. Moreover, 90%, 83%, 57%, and 3% of sampled soil, wheat, rice, and vegetable of Cd were higher than national allowable limits of China, respectively, indicating smelting induced serious environmental Cd pollution. Especially, higher Cd accumulation occurred in wheat compared to rice by factors of 1.5-2.0. However, as for Cd exposure to local residents, due to rice as staple food, rice intake ranked as main route and accounted for 49-53% of total intake, followed by wheat and vegetable. Cd exposure showed high potential noncarcinogenic risks with hazard quotient (HQ) of 0.63-4.99 using Monte Carlo probabilistic simulation, mainly from crop food consumption (mean 94% totality). Further, residents' hair Cd was significant correlated with HQ of wheat and rice ingestion, highlighting negative impact of cereal pollution to resident health. Therefore, smelting process should not coexist with cereal cultivating.

Sulfide-modified nanozerovalent iron for rapid decontamination of Cu(â ¡) complexes in high-salinity wastewater.

Heavy metal complexes receive less attention, but they are more difficult to remove than the free heavy metals. Moreover, the high-salinity wastewaters from various industries hinder the removal of heavy metal complexes. Removal of the metal complexes is a top priority but a challenging task. Herein, a new strategy for removing Cu-EDTA from high-salinity wastewater with sulfide-modified nanozerovalent iron (S-NZVI) was proposed. The S-NZVI exhibited a considerable adsorption capacity for Cu-EDTA (∼83 mg Cu/g) at a high salt concentration (25 g/L NaCl). Similarly, the S-NZVI maintained excellent adsorption performance (∼83 mg Cu/g) in the presence of CaCl2, MgCl2, Na2SO4, and NaNO3 (25 g/L). The S-NZVI showed extremely high efficiency for Cu-EDTA removal; 50 mg/L of Cu-EDTA was almost completely removed in 1 min, and the kobs was approximately 1.5 g/(mg min). The S-NZVI showed an extensive pH working range, and within the pH range of 2-9, the Cu-EDTA was removed completely within 5 min. The excellent removal performance of the S-NZVI was due to the high reactivity and high affinity of NZVI for Cu, as well as the special substitution of Fe2+ and the interfacial reactions between S-NZVI and the copper complexes. Compared with other studies of Cu complex removal, removal with S-NZVI was a simpler process with higher efficiency. In brief, S-NZVI efficiently removed Cu complexes from harsh water environments and was reused many times. The process was simple and efficient and has broad application prospects.

Pollution Status and Associated Risk Assessment of Heavy Metals in Sewage Sludge in the Yangtze River Delta, China.

The risk assessment of heavy metals (HMs) in sewage sludge (SS) is essential before land application. Six HMs in nineteen SS collected in the Yangtze River Delta were analyzed to assess risks to environment, ecosystem, and human health. HMs concentrations were ranked in the order of Zn > Cu > Cr > Ni > Pb > Cd, with Cu, Zn, and Ni in a total of 16% of samples exceeding the legal standard. Zn showed greatest extractability according to EDTA-extractable concentrations. HMs in 16% of SS samples posed heavy contamination to the environment with Zn as the major pollutant. HMs in 26% of samples posed ecological risk to the ecosystem and Cd was the highest risky HM. The probabilistic health risk assessment revealed that HMs posed carcinogenic risks to all populations, but non-carcinogenic risks only to children. This work will provide fundamental information for land application of SS in this area.

Interaction between mitochondrial homeostasis and barrier function in lipopolysaccharide-induced endothelial cell injury.

This study aimed to investigate the effects of mitochondrial homeostasis on lipopolysaccharide (LPS)-induced endothelial cell barrier function and the mechanisms that underlie these effects. Cells were treated with LPS or oligomycin (mitochondrial adenosine triphosphate synthase inhibitor) and the mitochondrial morphology, mitochondrial reactive oxygen species (mtROS), and mitochondrial membrane potential (ΔΨm) were evaluated. Moreover, the shedding of glycocalyx-heparan sulphate (HS), the levels of HS-specific degrading enzyme heparanase (HPA), and the expression of occludin and zonula occludens (ZO-1) of Tight Junctions (TJ)s, which are mediated by myosin light chain phosphorylation (p-MLC), were assessed. Examining the changes in mitochondrial homeostasis showed that adding heparinase III, which is an exogenous HPA, can destroy the integrity of glycocalyx. LPS simultaneously increased mitochondrial swelling, mtROS, and ΔΨm. Without oligomycin effects, HS, HPA levels, and p-MLC were found to be elevated, and the destruction of occludin and ZO-1 increased. Heparinase III not only damaged the glycocalyx by increasing HS shedding but also increased mitochondrial swelling and mtROS and decreased ΔΨm. Mitochondrial homeostasis is involved in LPS-induced endothelial cell barrier dysfunction by aggravating HPA and p-MLC levels. In turn, the integrated glycocalyx protects mitochondrial homeostasis.

[Effect of proprotein convertase subtilisin/kexin type 9 on platelet activation associated with sepsis].

OBJECTIVE: To investigate the effect of proprotein convertase subtilisin/kexin type 9 (PCSK9) on platelet activation in sepsis. METHODS: (1) Clinical trial: a prospective study was conducted. Patients with sepsis and septic shock aged ≥ 18 years old who met the diagnostic criteria of Sepsis-3 admitted to the department of intensive care medicine of the Affiliated Hospital of Binzhou Medical College from January to October in 2021 were selected as subjects. Healthy subjects in the same period were taken as healthy control group. Platelet count (PLT) in the first routine blood test after admission was recorded. Venous blood was taken 1 day after diagnosis, and serum PCSK9 level was determined by enzyme-linked immunosorbent assay (ELISA). The differences of PCSK9 level and PLT between the two groups were compared, and subgroup analysis was conducted based on PLT for patients with sepsis. The correlation between PCSK9 level and PLT in septic patients was analyzed by Pearson correlation method. (2) Animal experiment: 80 male C57BL/6 mice were randomly divided into control group, sepsis model group [lipopolysaccharide (LPS) group], PCSK9 inhibitor pretreatment group (PCSK9 inhibitor+LPS group) and PCSK9 inhibitor control group (PCSK9 inhibitor group), with 20 mice in each group. The mouse model of sepsis was reproduced by intraperitoneal injection of LPS 12 mg/kg, and the control group and PCSK9 inhibitor group were intraperitoneally injected with the same amount of sterile normal saline. PCSK9 inhibitor+LPS group and PCSK9 inhibitor group were pretreated with PCSK9 inhibitor 5 mg/kg intraperitoneal injection for 7 days before injection of LPS or normal saline, respectively, and the control group and LPS group were injected with an equal amount of sterile normal saline. The lung tissues were taken for pathological and immunohistochemical observation 24 hours after modeling. Blood was taken from the heart for determining PLT. Platelet activation was detected by flow cytometry. The expression level of platelet-activation marker CD40L was detected by Western blotting. RESULTS: (1) Clinical trial: there were 57 cases in the sepsis group and 27 cases in the healthy control group. Serum PCSK9 level in the sepsis group was significantly higher than that in the healthy control group (µg/L: 232.25±72.21 vs. 191.72±54.92, P < 0.05), and PLT was significantly lower than that in the healthy control group [×109/L: 146.00 (75.50, 204.50) vs. 224.00 (194.00, 247.00), P < 0.01]. Subgroup analysis showed that the serum PCSK9 level in the thrombocytopenia patients (n = 20) was significantly higher than that in the non-thrombocytopenia patients (n = 37; µg/L: 264.04±60.40 vs. 215.06±72.95, P < 0.01). Correlation analysis showed a significant negative correlation between serum PCSK9 levels and PLT in septic patients (r = -0.340, P = 0.010). (2) Animal experiment: there were no significant pathological changes in lung tissue in the control group and PCSK9 inhibitor group under light microscope, and no significant differences in PLT, platelet activation and plasma CD40L protein expression was found between the two groups. In the LPS group, a large number of inflammatory cells were infiltrated in the pulmonary interstitium, the alveolar structure was damaged obviously, the alveolar septum was widened, the alveolar cavity was extensively bleeding, the capillary dilatation with bleeding and platelet aggregation were found, the PLT was significantly decreased, the platelet activation and the expression level of CD40L protein in plasma were significantly increased. The infiltration of inflammatory cells in lung tissue of mice in the PCSK9 inhibitor+LPS group was reduced to a certain extent, the thickening of alveolar septa was reduced, the platelet aggregation in lung tissue was decreased as compared with the LPS group, the PLT was significantly increased (×109/L: 515.83±46.60 vs. 324.83±46.31, P < 0.05), the platelet activation and the expression level of CD40L protein in plasma were significantly decreased [positive expression rate of platelet activation dependent granule surface facial mask protein CD62P: (12.15±1.39)% vs. (18.33±2.74)%, CD40L protein (CD40L/ß-actin): 0.77±0.08 vs. 1.18±0.10, both P < 0.05]. CONCLUSIONS: PCSK9 level has a certain effect on promoting platelet activation in sepsis, and inhibition of PCSK9 level may have potential research value in improving adverse outcomes caused by sepsis thrombocytopenia.

High-Throughput Microfluidic Production of Droplets and Hydrogel Microspheres through Monolithically Integrated Microchannel Plates.

In this paper, we present a highly effective microfluidic emulsion system using an integrated microchannel plate (MCP), a porous glass membrane that is readily available and densely packs millions of through-microchannels, for high-throughput production of monodisperse droplets. The physical controls of droplet formation, including viscosity, flow rate, and pore size, have been extensively explored for optimum emulsification conditions. The performance of the device has been validated where monodisperse droplets with a narrow coefficient of variance (<5%) can be achieved at a dispersed phase flux of 3 mL h-1 from a piece of 4 × 4 mm2 MCP. The average droplet size is two times the nominal membrane pore diameter and thus can be easily controlled by choosing the appropriate membrane type. The preparation of hydrogel microspheres has also been demonstrated with a high throughput of 1.5 × 106 particles min-1. These microspheres with a uniform size range and rough surface morphology provide suitable bioenvironments and serve as ideal carriers for cell culture. Mouse fibroblasts are shown to be cultured on these 3D scaffolds with an average cell viability of over 96%. The cell attachment rate can reach up to 112 ± 7% in 24 h and the proliferation ability increases with the number of culture days. Furthermore, the device has been applied in the droplet digital polymerase chain reaction for absolute quantification of lung cancer-related PLAU genes. The detection limit achieved was noted to be 0.5 copies/µL with a dynamic range of 105 ranging from 1 × 102 to 1 × 106 copies/µL. Given the easy fabrication, robust performance, and simple operation, the emulsion system sets the stage for the laboratory's droplet-based assays and applications in tissue engineering.

Immobilization of zinc and cadmium by biochar-based sulfidated nanoscale zero-valent iron in a co-contaminated soil: Performance, mechanism, and microbial response.

Mining and smelting of mineral resources causes excessive accumulation of potentially toxic metals (PTMs) in surrounding soils. Here, biochar-based sulfidated nanoscale zero-valent iron (SNZVI/BC) was designed via a one-step liquid phase reduction method to immobilize cadmium (Cd) and zinc (Zn) in a copolluted arable soil. A 60 d soil incubation experiment revealed that Cd and Zn immobilization efficiency by 6 % SNZVI/BC (25.2-26.2 %) was higher than those by individual SNZVI (13.9-18.0 %) or biochar (14.0-19.3 %) based on the changes in diethylene triamine pentaacetic acid (DTPA)-extractable PTM concentrations in soils, exhibiting a synergistic effect. Cd2+ or Zn2+ replaced isomorphously Fe2+ in amorphous ferrous sulfide, as revealed by XRD, XPS, and high-resolution TEM-EDS, forming metal sulfide precipitates and thus immobilizing PTMs. PTM immobilization was further enhanced by adsorption by biochar and oxidation products (Fe2O3 and Fe3O4) of SNZVI via precipitation and surface complexation. SNZVI/BC also increased the concentration of dissolved organic carbon and soil pH, thus stimulating the abundances of beneficial bacteria, i.e., Bacilli, Clostridia, and Desulfuromonadia. These functional bacteria further facilitated microbial Fe(III) reduction, production of ammonium and available potassium, and immobilization of PTMs in soils. The predicted function of the soil microbial community was improved after supplementation with SNZVI/BC. Overall, SNZVI/BC could be a promising functional material that not only immobilized PTMs but also enhanced available nutrients in cocontaminated soils.

Remediation of lead and cadmium co-contaminated mining soil by phosphate-functionalized biochar: Performance, mechanism, and microbial response.

The remediation of heavy metals contaminated soils is of great significance for reducing their risk to human health. Here, pristine pinewood sawdust biochar (BC) and phosphate-functionalized biochar (PBC) were conducted to investigate their immobilization performance towards lead (Pb) and cadmium (Cd) in arable soils severely polluted by Pb (9240.5 mg kg-1) and Cd (10.71 mg kg-1) and microbial response in soils. Compared to pristine BC (2.6-12.1%), PBC was more effective in immobilizing Pb and Cd with an immobilization effectiveness of 45.2-96.2% after incubation of 60 days. Moreover, the labile Pb and Cd in soils were transformed to more stable species after addition of PBC, reducing their bioavailability. The immobilization mechanisms of Pb and Cd by PBC were mainly to facilitate the formation of stable phosphate precipitates e.g., Cd3(PO4)2, Cd5(PO4)3OH, Cd5H2(PO4)4‧4H2O, and pyromorphite-type minerals. Further, PBC increased pH, organic matter, cation exchange capacity, and available nutrients (phosphorus and potassium) in soils. High-throughput sequencing analysis of 16 S rRNA genes indicated that the diversity and composition of bacterial community responded to PBC addition due to PBC-induced changes in soil physicochemical properties, increasing the relative abundance of beneficial bacteria (e.g., Brevundimonas, Bacillus, and norank_f__chitinophagaceae) in the treated soils. What's more, these beneficial bacteria could not only facilitate Pb and Cd immobilization but also alter nutrient biogeochemical transformation (nitrogen and iron) in co-contaminated soils. Overall, PBC could be a promising material for immobilization of Pb and Cd and the simultaneous enhancement of soil quality and available nutrients in co-contaminated mining soils.

LC-MS/MS Based Volatile Organic Compound Biomarkers Analysis for Early Detection of Lung Cancer.

(1) Background: lung cancer is the world's deadliest cancer, but early diagnosis helps to improve the cure rate and thus reduce the mortality rate. Annual low-dose computed tomography (LD-CT) screening is an efficient lung cancer-screening program for a high-risk population. However, LD-CT has often been characterized by a higher degree of false-positive results. To meet these challenges, a volatolomic approach, in particular, the breath volatile organic compounds (VOCs) fingerprint analysis, has recently received increased attention for its application in early lung cancer screening thanks to its convenience, non-invasiveness, and being well tolerated by patients. (2) Methods: a LC-MS/MS-based volatolomics analysis was carried out according to P/N 5046800 standard based breath analysis of VOC as novel cancer biomarkers for distinguishing early-stage lung cancer from the healthy control group. The discriminatory accuracy of identified VOCs was assessed using subject work characterization and a random forest risk prediction model. (3) Results: the proposed technique has good performance compared with existing approaches, the differences between the exhaled VOCs of the early lung cancer patients before operation, three to seven days after the operation, as well as four to six weeks after operation under fasting and 1 h after the meal were compared with the healthy controls. The results showed that only 1 h after a meal, the concentration of seven VOCs, including 3-hydroxy-2-butanone (TG-4), glycolaldehyde (TG-7), 2-pentanone (TG-8), acrolein (TG-11), nonaldehyde (TG-19), decanal (TG-20), and crotonaldehyde (TG-22), differ significantly between lung cancer patients and control, with the invasive adenocarcinoma of the lung (IAC) having the most significant difference. (4) Conclusions: this novel, non-invasive approach can improve the detection rate of early lung cancer, and LC-MS/MS-based breath analysis could be a promising method for clinical application.

Intelligent analysis of excitation-emission matrix fluorescence fingerprint to identify and quantify adulteration in camellia oil based on machine learning.

Camellia oil (CAO) is a premium edible vegetable oil with medical value and biological activity, but it is susceptible to adulteration. Therefore, the demand for intelligent analysis to decipher the category and proportion of adulterated oil in CAO was the main driver of this work. Excitation-emission matrix fluorescence (EEMF) spectra of 933 vegetable oil samples were characterized by a chemometric method to obtain chemically meaningful information. Authenticity identification models were constructed using four machine learning methods to realize the discrimination of oil species adulterated in CAO mixtures. Meanwhile, quantitative models were established aiming at the fraud of CAO proportion in blended oil. Results showed that the specially constructed CNN obtained the optimal performance when evaluating unseen real-world samples, with a classification accuracy of 95.8% and 92.2%, and mean-absolute quantitative errors between 2.6 and 6.7%. Therefore, EEMF fingerprints coupled with machine learning are expected to provide intelligent and accurate analysis for authenticity detection of CAO.

Breast cancer cell-derived microRNA-155 suppresses tumor progression via enhancing immune cell recruitment and antitumor function.

Evidence suggests that increased microRNA-155 (miR-155) expression in immune cells enhances antitumor immune responses. However, given the reported association of miR-155 with tumorigenesis in various cancers, a debate is provoked on whether miR-155 is oncogenic or tumor suppressive. We aimed to interrogate the impact of tumor miR-155 expression, particularly that of cancer cell-derived miR-155, on antitumor immunity in breast cancer. We performed bioinformatic analysis of human breast cancer databases, murine experiments, and human specimen examination. We revealed that higher tumor miR-155 levels correlate with a favorable antitumor immune profile and better patient outcomes. Murine experiments demonstrated that miR-155 overexpression in breast cancer cells enhanced T cell influx, delayed tumor growth, and sensitized the tumors to immune checkpoint blockade (ICB) therapy. Mechanistically, miR-155 overexpression in breast cancer cells upregulated their CXCL9/10/11 production, which was mediated by SOCS1 inhibition and increased phosphorylated STAT1 (p-STAT1)/p-STAT3 ratios. We further found that serum miR-155 levels in breast cancer patients correlated with tumor miR-155 levels and tumor immune status. Our findings suggest that high serum and tumor miR-155 levels may be a favorable prognostic marker for breast cancer patients and that therapeutic elevation of miR-155 in breast tumors may improve the efficacy of ICB therapy via remodeling the antitumor immune landscape.

Fermented milk of cheese-derived Lactobacillus delbrueckiisubsp.bulgaricus displays potentials in alleviating alcohol-induced hepatic injury and gut dysbiosis in mice.

An isolate of Lactobacillus delbrueckii subsp. bulgaricus (L. bulgaricus L7) with robust antioxidant capacity was screened from traditional fermented Xinjiang cheese. Here, we focused on evaluating the effect of L. bulgaricus fermented milk on acute alcoholic liver disease prevention using a mice model, with glutathione treated mice as positive control. The results showed that both fermented milk and glutathione feeding could relieve alcohol-induced oxidative stress and inflammatory responses significantly. However, fermented milk feeding seemed to hold more promise in restoring gut dysbiosis relative to glutathione. Enhanced abundance of potential pathogens, Porphyromonas sp. and Enterococcus sp., induced by alcohol was considerably attenuated by additional feeding of fermented milk. Different scenario was firstly observed when additionally fed with glutathione in this study, showing remarkably increased abundance of Bacteroides sp. and Enterococcus sp. Our results suggested the more robust capability of L. bulgaricus fermented milk in restoring alcohol-induced gut dysbiosis relative to glutathione, indicating its potential protective effects on alcohol-induced hepatic injury.

Pyrolysis temperature and feedstock affected Cr(VI) removal capacity of sulfidated zerovalent iron: Importance of surface area and electrical conductivity.

Herein, feedstock (pinewood, rice straw, and dairy manure) and pyrolysis temperature (300, 500, and 700 °C) were selected as the influencing factors of properties of biochar (BC) to identify the contribution of biochar's matrix on Cr(VI) removal by BC-supported sulfidated zero-valent iron (S-ZVI/BC). Results showed that higher temperature was more conducible to improve the electrochemical properties and specific surface areas of composites. Raman spectra of S-ZVI supported by pinewood-derived BC (S-ZVI/PBC) showed the ID/IG ratio increased from 0.639 to 0.975 for the composites prepared at 300-700 °C, indicating the increased structural defects and resulting in the greatest Cr(VI) removal (35.81 mg g-1) and reduction (30.21 mg g-1) amounts of S-ZVI/PBC700. Besides, S-ZVI/PBC exhibited greater electrochemical reactivity and surface area than S-ZVI harbored by BC from dairy manure and rice straw. Additionally, Pearson correlation analysis revealed that Cr(VI) removal was significantly positively correlated to surface area (R2 = 0.90) and negatively correlated to Tafel corrosive potential (R2 = 0.88). Both desorption experiment and XPS spectra of spent sorbents showed that reduction predominated the detoxifying mechanism of Cr(VI) followed by adsorption (due to corrosively-generated iron oxides and BC) and precipitation (Cr2S3). This suggested that biochar with greater specific surface area and electrical conductivity is more favorable to immobilize S-ZVI with respect to Cr(VI) removal.

Association between plasma glycocalyx component levels and poor prognosis in severe influenza type A (H1N1).

Influenza A virus infection causes a series of diseases, but the factors associated with disease severity are not fully understood. Disruption of the endothelial glycocalyx contributes to acute lung injury in sepsis, but has not been well studied in H1N1 influenza. We aim to determine whether the plasma glycocalyx components levels are predictive of disease severity in H1N1 influenza. This prospective observational study included 53 patients with influenza A (H1N1) during the influenza season, and 30 healthy controls in our hospital. Patients were grouped by severity and survival. We collected clinical data and blood samples at admission. Inflammatory factors (tumor necrosis factor-α, interleukin-6, interleukin-10) and endothelial glycocalyx components (syndecan-1, hyaluronan, heparan sulfate) were measured. The plasma levels of syndecan-1, hyaluronan, and heparan sulfate were significantly higher in patients with severe influenza A (H1N1) than in mild cases. Syndecan-1 and hyaluronan were positively correlated with disease severity, which was indicated by the APACHE II and SOFA scores and lactate levels, and negatively correlated with albumin levels. At a cutoff point ≥ 173.9 ng/mL, syndecan-1 had a 81.3% sensitivity and 70.3% specificity for predicting of 28-day mortality. Kaplan-Meier analysis demonstrated a strong association between syndecan-1 levels and 28-day mortality (log-rank 11.04, P = 0.001). Elevated plasma levels of syndecan-1 has a potential role in systemic organ dysfunction and may be indicative of disease severity in patients with influenza A (H1N1).

Carbon matrix of biochar from biomass modeling components facilitates electron transfer from zero-valent iron to Cr(VI).

Biochar-harbored zero-valent iron (ZVI/BC) has been extensively used to detoxify hexavalent chromium (Cr(VI)). However, the role played by biochar in promoting electron transfer of ZVI and Cr(VI) reduction was not fully uncovered. Herein, three biomass modeling components (cellulose, hemicellulose, and lignin) and their blends were utilized to synthesize ZVI/BC via co-pyrolysis with hematite. X-ray diffraction analysis showed that hematite was successfully reduced to ZVI in nitrogen ambience. Batch sorption experiment showed that mass ratio (hematite to lignocellulosic component) of 1:20 is most optimal for reduction of Cr(VI) by ZVI/BCs. ZVI supported by BC derived from cellulose, hemicellulose, and their binary mixture demonstrated better Cr(VI) removal capacity (23.8-38.3 mg g-1) owing to higher ordered and graphitic carbon structure as revealed by Raman spectrum. In addition, lower Tafel corrosion potentials and smaller electrochemical impedance arc radiuses were observed based on electrochemical analysis, suggesting their higher electrical conductivity and faster electron transfer, whereas the BCs derived from lignin and lignin-containing hybrids were not conducive to electron transfer of ZVI due to lower degree of graphitization, thus compromising Cr(VI) removal by ZVI/BC (7.7-17.7 mg g-1). As per X-ray photoelectron spectroscopy analysis, reduction, complexation, and co-precipitation were the main mechanisms for Cr(VI) removal. The present study provided a scientific evidence for screening plant-derived biomass feedstock with high contents of cellulose and hemicellulose and low lignin content to fabricate ZVI/BC to achieve high Cr(VI) removal.

The significant role of electron donating capacity and carbon structure of biochar to electron transfer of zerovalent iron.

Herein, the major biochar properties were correlated with electron transfer of zerovalent iron (ZVI) and contribution of biomass constituents to biochar property was ascertained to optimize electron transfer of ZVI. To this end, five respective stalk-type and wood-type lignocellulosic biomasses were pyrolzed at 600 °C to prepare biochars to harbor ZVI (ZVI/BC). Thermogravimetric analysis demonstrated woody biomasses decomposed more intensively at higher temperature relative to stalky biomass. ZVI/BC were characterized with Raman, X-ray diffraction, and electrochemical analyses including electron donating capacity (EDC) and electron accepting capacity (EAC). Pearson correlation and partial least-squares (PLS) analyses confirmed that Cr(VI) reduction capacity was negatively related to Tafel corrosion potential and intensity ratio of ID/IG, but significantly positively-related to EDC of BC, in which EDC was a predominant attribute to contribute to reductive capacity toward Cr(VI) reduction. That is, greater EDC and higher graphitic carbon structure of biochar due to cellulose and hemicellulose components favor electron transfer of ZVI toward Cr(VI) reduction.

Effects of CRRT on renal function and toxin clearance in patients with sepsis: a case-control study.

OBJECTIVE: To explore the effects of continuous renal replacement therapy (CRRT) on renal function and toxin clearance in patients with sepsis and concurrent acute kidney injury (AKI). METHOD: A retrospective analysis was performed using the medical records of 115 patients with sepsis and AKI. Among them, 60 patients received routine treatment (group A) and 55 patients received CRRT plus routine treatment (group B). RESULT: After treatment, the clearance rates of serum creatinine, lactic acid, and urea nitrogen were significantly lower in group A than in group B. The decrease in high-sensitivity C-reactive protein and tumor necrosis factor-α levels after treatment was significantly higher in group B than in group A. For the Acute Physiology Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores from the two groups, the scores were significantly lower in group B than in group A. The mortality rate within 28 days was significantly higher in group A than in group B. CONCLUSION: CRRT can effectively improve the condition of patients with sepsis and AKI, promote elimination of toxins (serum creatinine, lactic acid, and urea nitrogen) from the body, and reduce the mortality rate.