rIL-35 prevents murine transfusion-related acute lung injury by inhibiting the activation of endothelial cells.

BACKGROUND: Transfusion-related acute lung injury (TRALI) is an important cause of death associated with transfusion, and no specific clinical treatments are available. Endothelial cells are believed to play an important role in the development of TRALI. This study investigated whether IL-35, an endothelial stabilizing cytokine could regulate the severity of antibody-mediated TRALI in vivo. STUDY DESIGN AND METHODS: Human microvascular endothelial cells (HMVECs) were cultured in vitro, rIL-35(2 µg/mL) was added before HMVECs activation, and HMVECs were fully activated by LPS (0.5 µg/mL). Then cells were collected for flow cytometry analysis. We used a previously established "two-event" mouse model of TRALI with naive and lipopolysaccharide (LPS)-injected mice as controls. rIL-35(100 µg/kg) was injected into the tail vein for 3 consecutive days before the induction of the TRALI model. Samples were collected 2 hours after TRALI induction and tested for lung tissue myeloperoxidase activity, total protein levels, lung tissue histology, endothelial cell activation assay, and cytokine assay. RESULTS: In vitro culture of HMVECs with rIL-35 verified that rIL-35 inhibited endothelial cells. In a mouse model, prophylactic administration of rIL-35 prevented pulmonary edema, increased lung protein levels, and reduced polymorphonuclear neutrophil accumulation in the lung. CONCLUSIONS: This work suggests that antibody-mediated murine TRALI can be prevented by rIL-35, and that rIL-35 appears to work by inhibiting the activation of lung endothelial cells.

Characteristics and serological patterns of COVID-19 convalescent plasma donors: optimal donors and timing of donation.

BACKGROUND: The lack of effective treatments against the 2019 coronavirus disease (COVID-19) has led to the exploratory use of convalescent plasma for treating COVID-19. Case reports and case series have shown encouraging results. This study investigated SARS-CoV-2 antibodies and epidemiological characteristics in convalescent plasma donors, to identify criteria for donor selection. METHODS: Recovered COVID-19 patients, aged 18-55 years, who had experienced no symptoms for more than 2 weeks, were recruited. Donor characteristics such as disease presentations were collected and SARS-CoV-2 N-specific IgM, IgG, and S-RBD-specific IgG levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Whereas levels of N-specific IgM antibody declined after recovery, S-RBD-specific and N-specific IgG antibodies increased after 4 weeks from the onset of symptoms, with no significant correlation to age, sex, or ABO blood type. Donors with the disease presentation of fever exceeding 38.5°C or lasting longer than 3 days exhibited higher levels of S-RBD-specific IgG antibodies at the time of donation. Of the 49 convalescent plasma donors, 90% had an S-RBD-specific IgG titer of ≥1:160 and 78% had a titer of ≥1:640 at the time of plasma donation. Of the 30 convalescent plasma donors, who had donated plasma later than 28 days after the onset of symptoms and had a disease presentation of fever lasting longer than 3 days or a body temperature exceeding 38.5°C, 100% had an S-RBD-specific IgG titer of ≥1:160 and 93% had a titer of ≥1:640. CONCLUSION: This study indicates that the S-RBD-specific IgG antibody reaches higher levels after 4 weeks from the onset of COVID-19 symptoms. We recommend the following selection criteria for optimal donation of COVID-19 convalescent plasma: 28 days after the onset of symptoms and with a disease presentation of fever lasting longer than 3 days or a body temperature exceeding 38.5°C. Selection based on these criteria can ensure a high likelihood of achieving sufficiently high S-RBD-specific IgG titers.

m6A Methylation-Mediated Stabilization of LINC01106 Suppresses Bladder Cancer Progression by Regulating the miR-3148/DAB1 Axis.

BACKGROUND: The pivotal roles of long noncoding RNAs (lncRNAs) in the realm of cancer biology, inclusive of bladder cancer (BCa), have been substantiated through various studies. Remarkably, RNA methylation, especially m6A modification, has demonstrated its influence on both coding and noncoding RNAs. Nonetheless, the explicit impact of RNA methylation on lncRNAs and its subsequent contribution to the progression of BCa remains to be elucidated. METHODS: In the present investigation, we scrutinized the expression and m6A methylation status of LINC01106, employing quantitative real-time PCR (qRT-PCR) and methylated RNA immunoprecipitation (MeRIP)-qPCR. To decipher the regulatory mechanism underpinning LINC01106, we utilized RNA immunoprecipitation (RIP)-qPCR, methylated RNA immunoprecipitation (MeRIP) assays, and bioinformatic analysis. Furthermore, the CRISPR/dCas13b-METTL3-METTL14 system was implemented to probe the function of LINC01106. RESULTS: The findings of our study indicated that LINC01106 is under expressed and exhibits diminished m6A methylation levels in BCa tissues when compared those of normal controls. A diminished expression of LINC01106 was associated with a less favorable prognosis in BCa patients. Intriguingly, CRISPR-mediated hypermethylation of LINC01106, facilitated by dCas13b-M3-M14, abolished the malignant phenotype of the BCa cells, an effect that could be inverted by Disabled-1 (DAB1) knockdown. From a mechanistic standpoint, we identified an m6A modification site on LINC01106 and highlighted YTHDC1 as a potential reader protein implicated in this process. Additionally, a positive correlation between DAB1 and LINC01106 expression was observed, with miR-3148 potentially acting as a mediator in this relationship. CONCLUSIONS: In summary, our research unveils a suppressive regulatory role of the LINC01106/miR-3148/DAB1 axis in the progression of BCa and underscores the YTHDC1-mediated m6A modification mechanism in regards to LINC01106. These revelations propose a new therapeutic target for the management of BCa.

Comparison of the conventional tube and erythrocyte-magnetized technology in titration of red blood cell alloantibodies.

BACKGROUND: Erythrocyte alloantibodies are mainly produced after immune stimulation, such as blood transfusion, pregnancy, and transplantation, and are the leading causes of severe hemolytic transfusion reactions and difficulty in blood grouping and matching. Therefore, antibody screening is critical to prevent and improve red cell alloantibodies. Routine tube assay is the primary detection method of antibody screening. Recently, erythrocyte-magnetized technology (EMT) has been increasingly used in clinical practice. This study intends to probe the application and efficacy of the conventional tube and EMT in red blood cell alloantibody titration to provide a reference for clinical blood transfusion. AIM: To investigate the application value of conventional tube and EMT in red blood cell alloantibody titration and enhance the safety of blood transfusion practice. METHODS: A total of 1298 blood samples were harvested from blood donors at the Department of Blood Transfusion of our hospital from March 2021 to December 2022. A 5 mL blood sample was collected in tubing, which was then cut, and the whole blood was put into a test tube for centrifugation to separate the serum. Different red blood cell blood group antibody titers were simultaneously detected using the tube polybrene test, tube antiglobulin test (AGT), and EMT screening irregular antibody methods to determine the best test method. RESULTS: Simultaneous detection was performed through the tube polybrene test, tube AGT and EMT screening irregular antibodies. It was discovered that the EMT screening irregular antibody method could detect all immunoglobulin G (IgG) and immunoglobulin M (IgM) irregular antibodies, and the results of manual tube AGT were satisfactory, but the operation time was lengthy, and the equipment had a large footprint. The EMT screening irregular antibody assay was also conducted to determine its activity against type O Rh (D) red blood cells, and the outcomes were satisfactory. Furthermore, compared to the conventional tube method, the EMT screening irregular antibody method was more cost-effective and had significantly higher detection efficiency. CONCLUSION: With a higher detection rate, the EMT screening irregular antibody method can detect both IgG and IgM irregular antibodies faster and more effectively than the conventional tube method.

[Distribution of atmospheric particulate inorganic nitrogen in different weather conditions in the heating period in Qingdao].

The atmospheric aerosol samples were collected before and in the heating period during October 2007-April 2008 in Qingdao coastal region, and inorganic nitrogen components were analyzed using IC (Ion Chromatography). The results showed that the concentration of aerosol particles and particulate inorganic nitrogen components (NH4+, NO3-) were increased from 137.41 microg/m3, 2.48 microg/m3, 6.95 microg/m3 before to 250.34 microg/m3, 4.43 microg/m3, 10.28 microg/m3 in the heating period respectively. The concentrations of TSP (total suspended particles) and inorganic nitrogen in Qingdao were influenced by different weather conditions. The average concentration of TSP was 181.34 microg/m3 in sunny days during heating period, increased by 32.0% than before. But the nitrate and ammonium showed a value of 5.56 and 1.86 microg/m3 in sunny days, lower than that before heating, which mainly came from secondary aerosols. The average concentrations of TSP, nitrate and ammonium increased were 1-2 times higher in foggy days in heating period due to lower temperature, high humidity and accumulation of pollutants. The concentrations of TSP, nitrate and ammonium decreased in strong winds and temperature drop weather. The size distribution of aerosol particles and inorganic nitrogen, were influenced clearly by heating soot and ash. The size distribution of nitrate showed double peaks with a higher peak in accumulation mode (0.43-0.65 microm) and a lower one in coarse mode (3.3-4.7 microm) before heating, and the peak in the 'accumulation mode' shifted to 0.65-1.1 microm during heating period. NH4(+) -N, a major inorganic nitrogen component in the particulate matter, showed single peak in the "accumulation mode".

[Urea in aerosol and rainwater over the East China Sea in winter and spring].

Organic nitrogen is a quantitatively important component of fixed nitrogen in atmospheric aerosol and rainwater. Urea as a possible candidate of organic nitrogen component might have a significant influence to the marine ecosystem since its bioavailability and broad range of natural and anthropogenic sources. 23 total suspended particulate samples, 4 size-segregated particles samples and 10 rainwater samples collected over the East China Sea from Nov. to Dec., 2006 and Feb. to Mar., 2007 were applied to analyze the concentrations of urea, nitrate and ammonium in aerosols and rainwater, respectively. In winter and spring, the concentrations of urea nitrogen were from 0.2 nmol m(-3) to 17.7 nmolx m(-3) and 6.5 nmol x m(-3) to 14.6 nmol x m(-3) in bulk aerosols, respectively and the corresponding concentrations were from 7.8 miromol x L(-1) to 18.1 micromol x L(-1) and 12.1 micromol x L(-1) to 35.3 micromol x L(-1) in rainwater. In both aerosols and rainwater over the East China Sea, the concentrations of urea nitrogen were higher in spring than those in winter. Urea nitrogen in aerosols contributed about 5% to the three measured nitrogen species and it was about 20% in rainwater. The size distribution of urea was markedly different from those of nitrate and ammonium,which had no pronounced difference among cascade stages. A slightly enhance urea contribution presented in the range of 0.43-0.65 microm in spring, which was 19.8%. In contrast, an enhancement presented in the range of 3.3-4.7 microm in winter, which was 19.8%. Factor analysis indicated that the sources of urea in aerosols were dominated by wind-blown soils in winter and sublime of urea in soils in spring, respectively.