Search

NF-κB activates the primary inflammatory response pathway responsible for methicillin-resistant Staphylococcus aureus (MRSA)-induced lung inflammation and injury. Here, we report that the Forkhead box transcription factor FOXN3 ameliorates MRSA-induced pulmonary inflammatory injury by inactivating NF-κB signaling. FOXN3 competes with IκBα for binding to heterogeneous ribonucleoprotein-U (hnRNPU), thereby blocking β-TrCP-mediated IκBα degradation and leading to NF-κB inactivation. FOXN3 is directly phosphorylated by p38 at S83 and S85 residues, which induces its dissociation from hnRNPU, thus promoting NF-κB activation. After dissociation, the phosphorylated FOXN3 becomes unstable and undergoes proteasomal degradation. Additionally, hnRNPU is essential for p38-mediated FOXN3 phosphorylation and subsequent phosphorylation-dependent degradation. Functionally, genetic ablation of FOXN3 phosphorylation results in strong resistance to MRSA-induced pulmonary inflammatory injury. Importantly, FOXN3 phosphorylation is clinically positively correlated with pulmonary inflammatory disorders. This study uncovers a previously unknown regulatory mechanism underpinning the indispensable role of FOXN3 phosphorylation in the inflammatory response to pulmonary infection.

Introduction: Autoimmune hemolytic anemia is a potentially lethal disease characterized by autoimmune hemolysis. Although human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have been reported as a promising therapy, there is limited evidence regarding warm autoimmune hemolytic anemia (wAIHA) patients. This study aimed to investigate the potential therapeutic effects of hUC-MSCs via immune regulation in wAIHA patients. Methods: Peripheral blood mononuclear cells (PBMCs) from 10 wAIHA patients and 8 healthy controls were isolated from peripheral blood and cultured for 3 days with or without the presence of hUC-MSCs; PBMCs were co-cultured with hUC-MSCs using Transwell assays. The supernatant cytokine levels were measured after culture through AimPlex Multiple Immunoassays for Flow, including IL-2, IL-4, IL-10, IFN-γ, TNF-α, and IL-17A. The percentages of regulatory T cells, regulatory B cells, and Th1/Th2 in PBMCs were also assessed before and after culturing. Results: In the wAIHA group, hUC-MSCs could upregulate the Treg and Breg proportions after culturing for 3 days, and the Treg and Breg percentages increased after co-culturing with hUC-MSCs in the wAIHA group compared with PBMC cultured alone for 3 days (8.29 ± 8.59 vs. 6.82 ± 1.32, 3.82 ± 1.87 vs. 1.75 ± 1.20, respectively). Compared with the PBMC wAIHA group, the levels of TNF-α (2.13 ± 2.07 vs. 16.20 ± 21.13 pg/mL, p = 0.019) and IL-10 (10.51 ± 18.42 vs. 37.78 ± 44.20 pg/mL, p = 0.012) were significantly elevated in the PBMC + hUC-MSCs wAIHA group. Conclusion: The hUC-MSCs contributed to the increasing proportion of regulatory cell populations in PBMCs of wAIHA patients, thereby potentially regulating autoimmune response; thus, hUC-MSCs may be a promising approach for wAIHA treatment.

Carbonaceous materials have proved to be effective in cadmium remediation, but their influences on soil microecology have not been studied well. Taking the structural differences and the maintenance of soil health as the entry point, we chose graphene (G), multi-walled carbon nanotubes (MWCNTs), and wetland plant-based biochar (ZBC) as natural and engineered carbonaceous materials to explore their effects on Cd fractions, nutrients, enzyme activities, and microbial communities in soils. The results showed that ZBC had stronger electronegativity and more oxygen-containing functional groups, which were related to its better performance in reducing soil acid-extractable cadmium (EX-Cd) among the three materials, with a reduction rate of 2.83–9.44%. Additionally, ZBC had greater positive effects in terms of improving soil properties, nutrients, and enzyme activities. Redundancy analysis and correlation analysis showed that ZBC could increase the content of organic matter and available potassium, enhance the activity of urease and sucrase, and regulate individual bacterial abundance, thereby reducing soil EX-Cd. Three carbonaceous materials could maintain the diversity of soil microorganisms and the stability of the microbial community structures to a certain extent, except for the high-dose application of ZBC. In conclusion, ZBC could better immobilize Cd and maintain soil health in a short period of time.

INTRODUCTION Neuromyelitis optica (NMO) is an autoimmune disease with a high rate of blindness and positive for the detection of aquaporin-4 antibody (AQP4) in most patients. NMO acute attacks are managed by high-doses of intravenous methylprednisolone followed by oral taper, and if symptoms fail to resolve, therapeutic plasma exchange (TPE) is added. TPE can remove pathological antibodies and inflammatory factors leading to clinical improvement. METHODS A total of 40 TPE fluid collections from the first to fifth TPE treatments were obtained from eight patients. Exosomes were isolated by ultracentrifugation. Mass spectrometry analyses were used to compare protein change in TPE fluid collection exosomes after the first to the fifth TPE treatments in these patients. RESULTS We detected 647 exosome proteins through data-independent acquisition analysis. It was found that some unknown functional antibody fragments and complement pathway proteins decreased after TPE treatment. The results revealed a significant involvement of the following two key pathways: the primary immunodeficiency and systemic lupus erythematosus that may be associated with NMO pathophysiology and TPE treatment efficacy (P

The removal or inactivation of circulating tumor cells (CTCs) can prevent distant metastasis by hematogenous route, but there is still a lack of mature and effective technical means. In the previous research, our team has initially established a method of riboflavin photosensitized treatment (RPT) for continuous treatment of peripheral blood in vitro for the inactivation of CTCs. The core of this technology is that it can selectively induce apoptosis of CTCs (HCT116 cells) without damaging immunocyte (mainly Peripheral Blood Mononuclear Cells，PBMCs) under specific parameters. To clarify the specific mechanism, firstly, the enrichment of riboflavin in HCT116 cells and PBMCs was observed under fluorescence microscope. Secondly, the apoptotic signaling pathways in HCT116 cells and PBMCs in response to RPT treatment were analyzed by transcriptomics. Finally, the mitochondrial damage in HCT116 cells and PBMCs before and after RPT treatment was observed under electron microscope. The results showed that under the same treatment conditions, HCT116 cells were significantly enriched in riboflavin compared with PBMCs. Besides, RPT treatment reduced the expression of long non﹣coding RNA (lncRNA) NEAT1, an effector gene of HCT116 cells, which further down-regulated the expression of target gene PAX2 and promoted the expression of Bax, leading to mitochondrial outer membrane permeabilization (MOMP), and consequently increased the release of pro-apoptotic factors such as cytochrome c(Cyt C), high-temperature requirement protein A2(HTRA2), apoptosis-inducing factor (AIF), endonuclease G(ENDOG), finally leading to apoptosis of HCT116 cells. In contrast, lncRNA NEAT1 remained unchanged in PBMCs before and after RPT treatment, and was unable to stimulate the PBMCs apoptotic signaling pathway. The results of the study indicated that under the specific treatment conditions, RPT technology could selectively induce apoptosis of HCT116 cells by activating the mitochondrial apoptosis pathway, which would further provide a theoretical and technical support for the effective inactivation of CTCs by RPT technology, thereby reducing the risk of recurrence of malignant tumors and improving the cure rate of malignant tumors.

Warfarin is a commonly used oral anticoagulant. Patients with artificial valve replacement, atrial fibrillation, pulmonary embolism, deep vein thrombosis, and other diseases require long-term anticoagulant oral treatment with warfarin. As warfarin exhibits prompt action with long maintenance time, it has become a key drug for the treatment of patients at risk of developing thrombosis or thromboembolism. Warfarin is a bican coumarin anticoagulant, that exhibits competitive action against vitamin K as its mechanism of action, thereby inhibiting the synthesis of coagulation factors-predominantly the vitamin K-dependent coagulation factors II, VII, IX, and X-in hepatocytes. Long-term warfarin is known to significantly increase the risk of organ bleeding in some patients, while some patients may need to reverse the anticoagulation effect. For instance, patients scheduled for emergency or invasive surgery may require rapid anticoagulation reversal. During such medical circumstances, fresh frozen plasma (FFP) is clinically used for the reversal of excess warfarin-associated anticoagulation, as it contains all the coagulation factors that can alleviate the abnormal blood anticoagulation status in such patients. Accordingly, this article aims to perform an in-depth review of relevant literature on the reversal of warfarin with FFP, and insightful deliberation of the application and efficacy of this clinical intervention.

Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease that ultimately leads to cirrhosis and hepatocellular carcinoma. Intermittent fasting has been proposed as a nonpharmacological dietary approach against metabolic diseases, including NAFLD. In this study, we aimed to investigate the effect of alternate day fasting (ADF) on high-fat diet (HFD)-induced NAFLD in C57BL/6 mice.A mouse model of fatty liver disease was established by feeding the mice a HFD for 16 weeks. The mice were administered by body weight, lipid accumulation and inflammation. PPARα, FGF21, serum triglycerides (TG), total cholesterol (TC), transaminase and lipogenesis were assessed.The results showed that long-term ADF can attenuate fatty liver disease by reducing hepatic inflammation and lipid accumulation in a mouse model. Meanwhile, fasting elevated the expression of serum and hepatic fibroblast growth Factor 21 (Fgf21), a circulating hormone produced predominantly in the liver, and could effectively prevent and ameliorate the pathogenesis of NAFLD. Serum starvation also enhanced Fgf21 expression and reduced free fatty acid (FFA)-induced lipid storage in hepatocytes. Moreover, refeeding inhibited the increase in Fgf21 expression induced by fasting. This fasted-to-refed transition is closely related to the expression of Fgf21. Further in vitro and in vivo studies showed that fasting-sensitive PPARα is indispensable for the expression of Fgf21 and its protective effect on NAFLD.These findings indicated that long-term ADF protects mouse livers against HFD induced fatty liver disease through controlling PPARα/Fgf21 signaling. In conclusion, ADF can emerge as a non-pharmacological dietary approach against fatty liver disease.

To study the serological, molecular and genetic characteristics of an individual with para-Bombay blood group.Serological method was used to detect the presence of A, B, H antigens in red blood cells and saliva, and Sanger sequencing was used to analyze the FUT1 gene of the proband and her family members. Genetic mechanism of the blood group was analyzed by pedigree analysis.Forward and reverse typing of the ABO blood group were inconsistent for the proband. A, B and H antigens were not found on erythrocytes, while B and H antigens were found in saliva, in addition with unexpected antibodies. The proband was found to have a genotype of ABO*B.01/ABO*O.01.04 caused by homozygous variant of c.948CA (p.Tyr316Ter) of the FUT1 gene.A novel para-Bombay blood group was identified, which was due to the missense variant of c.948CA in the coding region of the FUT1 gene, which has probably resulted in inability to synthesis active H antigen transferase.

Background Preoperative anemia is an important pillar of perioperative patient blood management. However, there was no literature comprehensively described the current situation of preoperative anemia in China. Methods We conducted a national retrospective cross-sectional study to assess the prevalence and intervention of preoperative anemia in Chinese adults. Data were from the National Preoperative Anemia Database based on hospital administration data from January 1, 2013 to December 31, 2018. Findings A total of 797,002 patients were included for analysis. Overall, 27.57% (95% CI 27.47–27.67) of patients had preoperative anemia, which varied by gender, age, regions, and type of operation. Patients who were female, age over 60 years old, from South China, from provinces with lower per capita GDP, underwent operations on the lymphatic and hematopoietic system, with laboratory abnormalities were more likely to have a high risk of preoperative anemia. Among patients with preoperative anemia, 5.16% (95% CI 5.07–5.26) received red blood cell transfusion, 7.79% (95% CI 7.67–7.91) received anemia-related medications such as iron, erythropoietin, folic acid or vitamin B12, and 12.25% (95% CI 12.10–12.40) received anemia-related therapy (red blood cell transfusion or anemia-related medications) before operation. The probability of preoperative RBC transfusion decreased by 54.92% (OR 0.46, 95% CI 0.46–0.47) as each 10-g/L increase in preoperative hemoglobin. Patients with preoperative hemoglobin less than 130 g/L was associated with longer hospital stay and more hospital costs. Patients with severe preoperative anemia given iron preoperatively had lower intra/post-operative RBC transfusion rate, shorter length of stay and less hospitalization costs, but no similar correlation was found in patients with mild and moderate preoperative anemia and patients given erythropoietin preoperatively. Interpretation Our present study shows that preoperative anemia is currently a relatively prevalent problem that has not been fully appreciated in China. More researches will be required to optimize the treatment of preoperative anemia. Funding National Natural Science Foundation of China and the Logistics Support Department of the Central Military Commission.

Exogenous silicon has been shown to enhance plant growth and alleviate heavy metals toxicity, but the regulation mechanism of silicon on cadmium migration and transformation in the soil-rice system is still unclear, which is worth further study. In this study, a pot experiment was carried out to explore the influence of different doses (0, 1 and 5%) of mineral silicon on soil properties, nutrient availability, rice growth, soil enzyme activities, Cd bioavailability, and uptake and accumulation of Cd in high-accumulating (H) and low-accumulating (L) rice cultivars grown in contaminated soils. Results showed that mineral-Si treatment could increase the total biomass and grain yield, with an increased rate of 17.7-27.3% and 14.7-19.1% for H; while 26.2-33.4% and 21.3-30.3% for L. Compared with non-mineral-Si treatment, the soil EX-Cd decreased by 3.9-13.3% (H) and 2.3-10.7% (L). Additionally, the Cd content in rice grain was significantly declined by 29.5-31.3% (H) and 34.9-35.2% (L). Mineral-Si enhanced urease, sucrase, and neutral phosphatase activities in both cultivars, but suppressed catalase activity in H. A selective change in bacterial community structure was observed under mineral-Si treatment, however, the bacterial community remained stable, suggesting that the mineral-Si had no adverse effect on the microbial community. The positive response of soil enzymes activities, rice growth and the overall stabilization of microbial environment for mineral-Si addition to the Cd contaminated soils indicated that mineral-Si could mitigate the risk of Cd and well maintain the soil health, proving it to be eco-friendly and low-cost amendment for soils remediation.

Light and small sprinklers were used to irrigate winter wheat fields. The distribution and migration of water and nitrogen in soil during winter wheat growth period were analyzed. Moreover, the growth traits of winter wheat were monitored. It is demonstrated that water–fertilizer coupling effect had a significant impact on the migration of water and nitrogen in soil and the growth traits of winter wheat under conditions of light and small sprinklers. Under the same condition of irrigation quota, although the content of moisture in soil was slightly reduced with the increase of the amount of fertilizer, the impact of the amount of fertilizer on the content of moisture in soil is much more insignificant than that of irrigation quota. The content of nitrate nitrogen (NO3--N) in soil was increased with an increasing amount of fertilizer, especially when the value of irrigation quota was low. On the other hand, under the same condition of amount of fertilizer, the content of nitrate nitrogen (NO3--N) in soil was decreased with an increasing value of irrigation quota, especially when the value of irrigation quota was high. Hence, an ultra-high value of irrigation quota will aggravate the leach of nitrate nitrogen in soil. The water–fertilizer coupling effect and yield of winter wheat could be optimized by improving irrigation scheme, optimizing irrigation quota, and optimizing the amount of fertilizer.

Background Platelet antibodies can lead to clinical diseases such as platelet transfusion refractoriness (PTR), fetal/neonatal alloimmune thrombocytopenia (FNAIT), etc. This study is aimed at understanding CD36 expression, platelet alloantibody distribution in different populations in Northern China, and effects of platelet alloantibodies on pregnancy. Study design and methods Whole blood samples of 612 subjects including hematological patients, pregnant women, and blood donors were collected at a single center, then CD36 expressions were determined, followed by platelet antibody screening and characterization of platelet antibody specificity. A retrospective analysis was performed in 1552 pregnant women admitted to Department of Obstetrics, in order to investigate FNAIT occurrence. Results Rate of CD36 deficiency expression was 2.12% (13/612), all cases exhibited type II deficiency without type I deficiency being detected, and such rate is lower than that in Southern China (3.43%), Japanese (4.87%) and in the black people (4.18%), and higher than that in the White people (0.09%). Positive rates of platelet antibody screening in hematological patient group (6.86%, 14/204) and in pregnant women group (6.31%, 13/206) are higher than that in blood donor group (0.49%, 1/202), P Conclusion The frequency of CD36 deficiency in northern China was low, all of them were type II deficiency, and no CD36 antibody was detected. It is speculated that the risk of immune-related thrombocytopenia caused by CD36 deficiency in this population is very low. Platelet antibodies should be monitored early in patients with hematological and multiple miscarriages pregnant.

Background Radiation and filtration have achieved satisfactory results in inactivation or removal of tumor cells mixed in salvage blood, but some drawbacks remain. This study evaluated the inactivation on HCT116 cells mixed in simulative salvage blood by riboflavin photochemical treatment. Methods HCT116 cells were added to the whole blood to simulate contaminated salvaged blood. The mixed blood was added with riboflavin of 50 μmol/L final concentration and illuminated by ultraviolet light. The samples were divided into control group and Experimental Groups 1 (18 J/cm2 ), 2 (23.4 J/cm2 ), and 3 (28.8 J/cm2 ). An autotransfusion system (Cell Saver Elite, Haemonetics) was used to simulate the intraoperative blood salvage procedure to deal with whole blood. The apoptosis rate and tumorigenicity of HCT116 cells and the superimposed damage to red blood cells (RBCs) were evaluated. Results The apoptosis rates of HCT116 in Experimental Groups 1, 2, and 3 were much higher than that in the control group. Tumor growth was found in the control group, but no tumor growth was found in the three experimental groups. The hemolysis rates in the three experimental groups were significantly higher than that in the control group, but much lower than the quality standard of RBCs at the end of preservation. The concentration of adenosine triphosphate in RBCs was comparable in the control and experimental groups. Conclusion Riboflavin at a 50 μmol/L final concentration and 18 J/cm2 ultraviolet illumination can effectively inactivate HCT116 cells in salvaged blood, with minimum damage to the structure and function of RBCs, and the main quality indexes of salvaged RBCs were within the standard range.

Surgical resection is one of the most common radical treatments for cancers. However, tumors may be compressed or the local intravascular pressure may be increased during surgical manipulation, causing the shedding and entry of tumor cells into the blood circulation and hence distant recurrence and metastasis of tumors. We have preliminarily established a method of riboflavin photosensitization treatment (RPT) for inactivation of circulating tumor cells. This technology promises to solve the problems of shedding and entry of solid tumor cells into blood circulation before surgical manipulation, and almost unavoidable hematogenous dissemination of tumor cells during surgical resection. In the present study, apoptosis detection and tumorigenicity experiment in immunodeficient mice were conducted to evaluate the effect of RPT for inactivation of circulating tumor cells respectively. Next, functional evaluation was carried out for the immune cells through detecting apoptosis rate and cytokine secretion of lymphocyte. Finally, thromboelastography (TEG) and free hemoglobin were detected to assess peripheral blood coagulation and red blood cell damage. The results showed that RPT (50 μmol/L riboflavin, 10.8 J/cm2 UV) could effectively make tumor cell lose the ability of proliferation in the peripheral blood. In the meantime, the damage caused to peripheral blood coagulation, immune cell function and red blood cells was generally acceptable. The results of the study showed that RPT had huge potential in addressing the problems of shedding and entry of solid tumor cells into blood circulation before surgical manipulation, and almost unavoidable hematogenous dissemination of tumor cells during surgical resection. This therapy is expected to be an auxiliary and supportive method to reduce the risk of hematogenous metastasis and recurrence of cancers, and to increase the surgical success rate of malignant solid tumors.

This paper described the development and application of a nitrifying bacteria sensor to monitor water toxicity. Four strains of bacteria with high efficiency nitrification, designated as F1, F4, Y2 and Z1, were isolated from fish pond sediment, and identified as Rhodococcus sp. (F1 and F4), Pseudomonas sp. (Y2) and Micrococcus sp. (Z1). The four bacterial strains were tested for their nitrifying capabilities. The results showed that the nitrifying rate of F1, F4, Y2 and Z1 reached 3.51, 3.43, 3.46, 3.52 mg/L·d respectively. The four strains were further cultivated for 21 days to investigate the effects of temperature, pH and inoculation amount on their NH4 +-N degradation ability. The cultivation showed that the four strains possessed optimal NH4 +-N degradation rate when temperature was 35?, pH value was 8.5, and inoculation amount was 30%. Furthermore, the carrier optimization test demonstrated that the nitrobacteria film prepared using 16% PVA, 1.2% SA, 2% NaNO3 and 75% CaCl2 had the best performance of toxicity detection. These results suggested that the nitrobacteria biosensor designed in this study was sensible and suitable for detecting water toxicity.

Antibody reagents have been remained as a standard approach to characterize blood group (BG) antigens in clinic. The specificity and cross-reactivity of these BG antibodies are routine detected using the gel microcolumn assay (GMA). However, the GMA is neither specific nor sensitive, thus increasing the risk of improperly matched RBC transfusions. In this work, we describe a bead-based RBC membrane antigen array to detect BG antibody-antigen binding with ∼700-fold higher sensitivity and dynamic range than the GMA. RBC membrane antigen arrays were fabricated using fragmented RBC membranes highly enriched in BG panel antigens. The arrays were then used to screen the interactions of 15 BG reagents to three antigen panels. The majority of the antibody reactions (i.e., 86.7%; 39/45) aligned with those obtained with the GMA. The six cross-reactive, nonspecific antibody reactions identified only by our arrays (i.e., 13.3%; 6/45) were confirmed by agglutination inhibition and genotyping assays. These results demonstrate that our RBC membrane antigen array has great potential in screening BG antibodies and improving the safety of RBC transfusions.

The aim of this study was to establish and to optimize the preparation technology of whole blood internal quality control (IQC) products for blood transfusion compatibility testing. Several B-type RhD-negative blood samples collected from healthy donors were mixed. Two groups of whole blood IQC products, namely, the preservative solution group (PS group) and the saline group, were prepared. The agglutination intensity of IQC sample red cells and anti-B antibody, IgM anti-A antibody and reverse-typing A cell, IgG anti-D and O-type RhD-positive red cells, as well as free hemoglobin concentration in the supernatant of the two groups were detected. The erythrocytes in both groups were damaged to a certain extent during storage, but no evident (above moderate) hemolysis was observed in the stored sample within 42 days. The red cells remained structurally complete and the reaction activity of IgG anti-D reagent remained generally unchanged (P>0.05). Although the reaction activity oscillation of IgM anti-A reagent was observed, the agglutination intensity varied within an acceptable range of 1+. No difference was observed between the preparation methods of the samples, i.e., between the erythrocyte washed with saline and the one washed with red cell preservative solution (P>0.05). The long shelf life, low variance between tubes and stable antigen-antibody reaction activity of the whole blood IQC products prepared using the proposed method can meet the requirements of blood transfusion compatibility testing.

To evaluate the effects of hydroformylation treatment on the storage time and blood group antigen expressions of reagent red blood cells (RBCs).RBCs from healthy donors were treated by using various final concentrations of paraformaldehyde (0.01%, 0.02%, 0.05%, 0.1%, 0.2%, 0.5% and 1.0%) and glutaraldehyde (0.01%, 0.025%, 0.05%, 0.1%, 0.2%, 0.5% and 1.0%), and one aliquot was used as control (untreated with aldehydes). Supernatant free hemoglobin (FHb) levels in all groups stored at 4 °C were detected every week, and the optimal procedure was selected. Expression of blood group antigens on RBCs treated by the optimal procedure was determined, and the total scores of blood group antigens were calculated.0.2%, 0.5% and 1.0% Glutaraldehyde groups were ruled out directly due to serious crosslinking and aggregation of RBCs. As the extension of time, FHb levels in other 11 groups gradually increased (p0.01 or p0.05). FHb level in 0.025% glutaraldehyde group was significantly lower than that in other groups after 13 weeks (p0.01), and the antigen strength of Fy(b), Jk(b), and Le(b) decreased slightly compared with those before treatment and storage (p0.05), and there was no significant change for antigen strength of A, B, D, C, E, c, e, M, N, S, s, k, P1, Fy(a), Jk(a), and Le(a) (p0.05).0.025% Glutaraldehyde treatment can provide optimal protection for the membrane of RBCs and keep hemolysis at a low level after 13 weeks storage, and the majority of blood group antigen systems are not significantly affected, and the slight decline of Fy(b), Jk(b), and Le(b) antigen strength was acceptable for classical serological tests.