Relationships of platelet glycoprotein specific antibody with therapeutic efficacy of short-term high-dose dexamethasone and bleeding score in the newly diagnosed adult patients with primary immune thrombocytopenia.

Objectives: We aimed to investigate relationships of platelet glycoprotein (GP) specific antibody with therapeutic efficacy of high-dose dexamethasone (HD-DXM) and bleeding score in primary immune thrombocytopenia (ITP) adults. Methods: A retrospective study was carried out to analyze relationships of polymorphism of GP specific antibody with initial therapeutic efficacy of HD-DXM and bleeding score of newly diagnosed ITP adults between 1 June, 2016 and 31 January, 2020. Results: 59 patients were involved in the study, with 33 cases of responders and 26 cases of non-responders between June 2016 and January 2020. At admission, there were 31 (52.5%) GP antibody-positive patients. Initial therapy of HD-DXM was effective for 78.6% GP antibody-negative patients and 35.5% GP antibody-positive patients, with a better therapeutic efficacy in patients with anti-GP Ib/IX antibody or anti-GP IIb/IIIa antibody but not in those with anti-GP Ib/IX antibody plus anti-GP IIb/IIIa antibody. Notably, therapeutic efficacy is much worse for minority (Uyghur) patients compared with corresponding Han patients. Similarly, it was much lower in GP antibody-positive patients compared with corresponding negative ones at low and medium bleeding score, with no response in GP antibody-positive patients at high bleeding score. Furthermore, there was a moderate negative correlation between therapeutic efficacy and GP-specific antibody (p < 0.05), but no obvious linear relationship between clinical bleeding degree and GP-specific antibody (p > 0.05). Conclusion: Collectively, the newly diagnosed ITP adults with GP-specific antibody have a poor response to short-term HD-DXM, especially in minority (Uyghur) patients with GP-specific antibody in China.

Enhancing Bone Grafting Outcomes: A Comprehensive Review of Antibacterial Artificial Composite Bone Scaffolds.

Bone defects and dysfunctions are prevalent among patients, resulting from various causes such as trauma, tumors, congenital malformations, inflammation, and infection. The demand for bone defect repair materials is second only to blood transfusions. Artificial bone composites offer numerous advantages for bone damage repair, including their availability, absence of rejection or immune reactions, high malleability, exceptional mechanical strength, and outstanding biocompatibility. However, bacterial infections frequently occur during bone transplantation or on graft material structures, leading to severe complications such as osteomyelitis and osteoporosis. Moreover, existing osteogenic materials alone are inadequate to address the challenges posed by traumatic infections, presenting a significant hurdle for clinicians in reconstructing infectious bone defects. Consequently, it is crucial to functionalize artificial bone composites to facilitate effective bone repair and regeneration. Notably, antibacterial capabilities play a critical role in preventing and treating infectious bone defects, and current research is focusing on the interface between artificial bone composites and antibacterial treatments. This article provides an extensive review of the current state of artificial composite bone scaffolds with antibacterial properties for infection prevention in bone grafting.

Imbalance of follicular regulatory T (Tfr) cells/follicular helper T (Tfh) cells in adult patients with primary immune thrombocytopenia.

This study is to investigate the role of follicular regulatory T (Tfr) cells/follicular helper T (Tfh) cells imbalance in adult patients with primary immune thrombocytopenia (ITP). Totally, 40 cases of primary ITP patients and 30 healthy controls were enrolled. Blood samples were collected from ITP patients (pre- and post-therapy) and controls. Flow cytometry was used to detect the proportion of Tfr and Tfh cells in peripheral blood. Real-time quantitative polymerase chain reaction (PCR) was performed to detect the mRNA expression levels of FOXP3, BCL-6, and BLIMP-1. Enzyme-linked immunosorbent assay (ELISA) was conducted to detect interleukin (IL)-10 and IL-21 levels. Spearman's correlation was used for correlation analysis. Compared with control, Tfr cell proportion, FOXP3 mRNA, and IL-10 were significantly decreased in the pre-therapy ITP group, but were significantly increased post-therapy. Tfh cell proportion, BCL-6 mRNA, and IL-21 were increased, while BLIMP-1 mRNA was decreased, in the pre-therapy ITP group than the control group. These effects were reversed in the post-therapy ITP group. Moreover, the Tfr/Tfh ratio was decreased in the pre-therapy ITP group than control group, whereas was increased in the post-therapy ITP group than the pre-therapy ITP group. Furthermore, Tfr cell proportion, FOXP3 mRNA, IL-10, and Tfr/Tfh ratio were positively correlated with the platelet count (PLT) in the ITP pre-therapy group. In addition, Tfh cell proportion, BCL-6 mRNA, and IL-21 were negatively correlated with the PLT, while BLIMP-1 mRNA was positively correlated with the PLT. Conclusively, Tfr cell proportion in peripheral blood is decreased and Tfh cell proportion is increased, leading to unbalanced Tfr/Tfh ratio in ITP patients pre-therapy. The imbalance of Tfr/Tfh is recovered post-therapy, suggesting that the Tfr and Tfh cells may be involved in ITP pathogenesis. The abnormal expression of FOXP3, BCL-6, and BLIMP-1 mRNA and the changes in IL-10 and IL-21 levels may be related to the imbalance of Tfr/Tfh.

The Role of Follicular Regulatory T Cells/Follicular Helper T Cells in Primary Immune Thrombocytopenia.

INTRODUCTION: Immune thrombocytopenia (ITP) is an autoimmune disease characterized by thrombocytopenia. Herein, we sought to identify potential immune-related therapeutic targets in ITP. METHODS: The differentially expressed genes (DEGs) between ITP patients and controls in GSE43177 and PRJNA299534 were analyzed. The intersections of the two DEG groups were screened as common genes, and enrichment analysis was performed. Additionally, differential analysis of immune cell levels between ITP and controls was performed. Changes in the proportions of T follicular helper (Tfh) and follicular regulatory T (Tfr) cells in peripheral blood samples from ITP patients, ITP patients responding to therapy, and healthy controls were identified. The expression changes in B-cell lymphoma (Bcl)-6 and interleukin (IL)-21 were further evaluated. RESULTS: A total of 76 common genes were identified, and enrichment analysis found that these genes were mainly associated with neutrophil-mediated immunity, the MAPK signaling pathway, and the FOXO signaling pathway. Furthermore, we found different levels of Tfh cells in patients with ITP and controls. The level of Tfh cells in the peripheral blood is significantly increased in ITP patients and declines after responding to therapy. The Tfr/Tfh ratio was reduced in ITP patients and increased after responding to therapy. IL-21 and Bcl-6 were more highly expressed in ITP patients than in controls. CONCLUSION: We identified abnormally expressed genes in ITP related to immune-related biological functions. We further identified the changes in Tfh and Tfr cells during ITP treatment. This provides a rationale for immunotherapy in ITP patients.

Alteration of birnessite reactivity in dynamic anoxic/oxic environments.

Although the oxidative capacity of manganese oxides has been widely investigated, potential changes of the surface reactivity in dynamic anoxic/oxic environments have been often overlooked. In this study, we showed that the reactivity of layer structured manganese oxide (birnessite) was highly sensitive to variable redox conditions within environmentally relevant ranges of pH (4.0 - 8.0), ionic strength (0-100 mM NaCl) and Mn(II)/MnO2 molar ratio (0-0.58) using ofloxacine (OFL), a typical antibiotic, as a target contaminant. In oxic conditions, OFL removal was enhanced relative to anoxic environments under alkaline conditions. Surface-catalyzed oxidation of Mn(II) enabled the formation of more reactive Mn(III) sites for OFL oxidation. However, an increase in Mn(II)/MnO2 molar ratio suppressed MnO2 reactivity, probably because of competitive binding between Mn(II) and OFL and/or modification in MnO2 surface charge. Monovalent cations (e.g., Na+) may compensate the charge deficiency caused by the presence of Mn(III), and affect the aggregation of MnO2 particles, particularly under oxic conditions. An enhancement in the removal efficiency of OFL was then confirmed in the dynamic two-step anoxic/oxic process, which emulates oscillating redox conditions in environmental settings. These findings call for a thorough examination of the reactivity changes at environmental mineral surfaces (e.g., MnO2) in natural systems that may be subjected to alternation between anaerobic and oxygenated conditions.

Impacts of environmental levels of hydrogen peroxide and oxyanions on the redox activity of MnO2 particles.

Despite the widespread presence of hydrogen peroxide (H2O2) in surface water and groundwater systems, little is known about the impact of environmental levels of H2O2 on the redox activity of minerals. Here we demonstrate that environmental concentrations of H2O2 can alter the reactivity of birnessite-type manganese oxide, an earth-abundant functional material, and decrease its oxidative activity in natural systems across a wide range of pH values (4-8). The H2O2-induced reductive dissolution generates Mn(II) that will re-bind to MnO2 surfaces, thereby affecting the surface charge of MnO2. Competition of Bisphenol A (BPA), used as a target compound here, and Mn(II) to interact with reactive surface sites may cause suppression of the oxidative ability of MnO2. This suppressive effect becomes more effective in the presence of oxyanions such as phosphate or silicate at concentrations comparable to those encountered in natural waters. Unlike nitrate, adsorption of phosphate or silicate onto birnessite increased in the presence of Mn(II) added or generated through H2O2-induced reduction of MnO2. This suggests that naturally occurring anions and H2O2 may have synergetic effects on the reactivity of birnessite-type manganese oxide at a range of environmentally relevant H2O2 amounts. As layered structure manganese oxides play a key role in the global carbon cycle as well as pollutant dynamics, the impact of environmental levels of hydrogen peroxide (H2O2/MnO2 molar ratio ≤ 0.3) should be considered in environmental fate and transport models.

Efficient removal of estrogenic compounds in water by MnIII-activated peroxymonosulfate: Mechanisms and application in sewage treatment plant water.

In this paper, the degradation of three endocrine-disrupting chemicals (EDCs): bisphenol A (BPA), 17ß-estradiol (E2) and 17α-ethinylestradiol (EE2) by manganite (γ-MnOOH) activated peroxymonosulfate (PMS) was investigated. Preliminary optimisation experiments showed that complete degradation of the three EDCs was achieved after 30 min of reaction using 0.1 g L-1 of γ-MnOOH and 2 mM of PMS. The degradation rate constants were determined to be 0.20, 0.22 and 0.15 min-1 for BPA, E2 and EE2, respectively. Combining radical scavenging approaches, Electron paramagnetic resonance (EPR) and X-ray photoelectron spectroscopy (XPS) analyses, we revealed for the first time that about 40% of EDCs degradation can be attributed to heterogeneous electron transfer reaction involving freshly generated Mn(IV), and 60% to sulfate radical degradation pathway. The influence of various inorganic ions on the γ-MnOOH/PMS system indicated that removal efficiency was slightly affected by chloride and carbonate ions, while nitrate and nitrite ions had negligible impacts. The application of γ-MnOOH/PMS system in real sewage treatment plant water (STPW) showed that degradation rate constants of EDCs decreased to 0.035-0.048 min-1 and complete degradation of the three EDCs after 45 min. This study provides new insights into the reactivity of combined γ-MnOOH and PMS, and opens new ways for the application of Mn-bearing species in wastewater treatment technologies.

Regulation of Th1/Th2 and Th17/Treg by pDC/mDC imbalance in primary immune thrombocytopenia.

This study investigates the regulatory effect of plasmacytoid dendritic cells (pDC)/myeloid dendritic cells (mDC) imbalance on balance of Th1/Th2 and Th17/Treg in primary immune thrombocytopenia (ITP). A total of 30 untreated ITP patients and 20 healthy controls were recruited. Compared with healthy control, the pDC proportion of ITP patients was significantly reduced (P = 0.004), while the mDC proportion was not significantly changed (P = 0.681), resulting in a decrease in the pDC/mDC ratio (P = 0.001). Additionally, compared with controls, serum levels of interleukin (IL)-6, IL-12, and IL-23 were increased in ITP patients (P < 0.001), and mRNA levels of IL-12p40, IL-12p35, and IL-23p19 were also increased (P =0.014, P = 0.043, P < 0.001). Compared with the healthy control, the proportion of Th1 and Th17 cells in ITP patients increased (P = 0.001, P = 0.031). Serum levels of interferon gamma (IFN-γ) and IL-17 in ITP patients also increased (P = 0.025, P = 0.005). Furthermore, T-bet and RORγt mRNA levels were increased in peripheral blood of ITP patients (P = 0.018, P < 0.001). Correspondingly, the proportion of Th2 and Treg cells decreased (P = 0.007, P < 0.001), along with a decrease in serum IL-4 and transforming growth factor beta (TGF-ß) (P = 0.028, P = 0.042), and an increase in GATA-3 mRNA (P < 0.001). However, there was no significant difference in Foxp3 mRNA levels (P = 0.587). Pearson correlation analysis showed that the proportion of total dendritic cells (DCs) was positively correlated with IL-12 (r = 0.526, P = 0.003) and IL-23 (r = 0.501, P = 0.005) in ITP patients. Th1/Th2 ratio, IFN-γ, and IL-12 levels were negatively correlated with platelet counts (r = -0.494, P = 0.009; r = -0.415, P = 0.028; r = -0.492, P = 0.032). However, IL-23 was positively correlated with IL-17 (r = 0.489, P = 0.006) and negatively correlated with platelet count (r = -0.564, P = 0.001). The ratio of IL-6 and Th17 cells was negatively correlated with platelet count (r = -0.443, P = 0.014; r = -0.471, P = 0.011). The imbalance of pDC/mDC and the increase of IL-6, IL-12, and IL-23 lead to the increased differentiation of CD4+ T cells into Th1 and Th17 cells, which might be the important mechanisms underlying the imbalance of Th1/Th2 and Th17/Treg in ITP patients.

Water Flow and Dissolved MnII Alter Transformation of Pipemidic Acid by Manganese Oxide.

Manganese oxides have been proposed as promising geomedia to remove trace organic contaminants in both natural soils and artificial infiltration systems. Although MnOx-based redox processes have been largely investigated, little is known on the effects of water flow and dissolved MnII on manganese-mediated redox reactions in saturated porous media. Here, we have demonstrated that the reactive transport of a widely used quinolone antibiotic, pipemidic acid (PIP), in MnO2-coated sand (MCS) columns is altered by the presence of dissolved MnII, generated in situ as reduced ions or present in inflow solution. Decreasing the flow rate or flow interruption facilitated oxidation reactions and generated redox byproducts (MnII and PIPox). However, preloading of MCS columns with dissolved MnII led to suppressed reactivity with PIP. When PIP and MnII are simultaneously injected, competition between PIP and MnII for binding at the edge sites takes place during the initial kinetic phase of reaction, while at a later breakthrough time MnII will occupy both edge and vacancy sites due to the continuous supply of MnII. We also developed a reactive transport model that accounts for adsorption kinetics to predict changes in transport behavior of antibiotics in the presence of different doses of dissolved MnII. This work has strong implications for an accurate assessment of the reactivity of manganese oxides used as engineered geomedia for quinolone remediation and in developing transport models of antibiotics in natural systems.

Stabilization of Foam Lamella Using Novel Surface-Grafted Nanocellulose-Based Nanofluids.

To solve the potential risk of present oilfield chemistries to subterranean environment, our group contributes to the development of "green" petroleum production processes. This proof-of-concept research studied the well-defined nanocellulose-based nanofluids, i.e., original (NC), AMPS grafted (NC-KY), and AMPS and hydrophobic chains grafted (NC-KYSS), in stabilizing foam lamella for potential use in enhanced oil recovery (EOR). The data showed that the collaboration of the surface-functional nanocellulose considerately improved the foam stability particularly in the presence of hydrocarbons due to the thickened foam film coupled with the molecular interactions at interior lamella. Since the grafted AMPS and alkyl chains, NC-KYSS noticeably enhanced foam quality compared against NC and NC-KY. With the increase in gas pressure, the lamella stabilizing effect of NC-KYSS became increasingly significant. The coflowing behaviors of foam with oleic phase in porous media were examined in a five-spot visualization micromodel (15 cm × 15 cm × 1 cm) and identified using a digital analysis method. The defoaming/destabilizing effect of hydrocarbons was fairly notable in porous media, causing the foam to finger through the formed "oil bank". However, a tough displacement front was constructed when the surfactant synergized with NC-KYSS due to the stabilized foam lamella and 12% of incremental oil recovery was produced.