Objective
To examine the expression and changes in function of circulating CD4+CXCR5+FoxP3+ follicular Treg (Tfr) cells in patients with active rheumatoid arthritis (RA) and in patients with RA in ...stable remission, and to clarify the role of Tfr cells in the pathogenesis of RA.
Methods
Levels of Tfr cells and follicular helper T (Tfh) cells in the peripheral blood of 39 patients with active RA, 39 patients with RA in stable remission, and 33 healthy controls were detected by flow cytometry. The function of Tfr cells was measured by coculturing them with Tfh cells and B cells. Activated CD45RA−FoxP3high Tfr cells were also analyzed. Clinical indicators, including serum Ig and autoantibody levels, were tested, and correlations with Tfr cells were systematically analyzed. The Disease Activity Score in 28 joints (DAS28) was calculated, and correlation analysis with Tfr cells was conducted.
Results
The level of CD4+CXCR5+FoxP3+ Tfr cells and the Tfr cell:Tfh cell ratio in peripheral blood from patients with RA in stable remission were significantly increased compared with the same measures in patients with active RA and in healthy controls. The function of Tfr cells was enhanced, and the activated CD45RA−FoxP3high Tfr cell subset was increased in patients with RA in stable remission compared with healthy controls. Furthermore, the number of Tfr cells in RA patients was inversely correlated with IgG, rheumatoid factor, and anti–cyclic citrullinated peptide as well as with the DAS28.
Conclusion
Circulating Tfr cells are increased as patients with RA achieve stable remission of disease, and increased Tfr cells can suppress autoimmunity in RA patients to stabilize their condition. Our results provide novel insight into RA pathogenesis.
Trastuzumab is commonly used in the treatment of human epidermal growth factor receptor-2 positive (HER-2+) breast cancer, but its efficacy is often limited by the emergence of chemoresistance. ...Recent studies indicate that exosomes act as vehicles for exchange of genetic cargo between heterogeneous populations of tumor cells, engendering a transmitted drug resistance for cancer development and progression. However, the specific contribution of breast cancer-derived exosomes is poorly understood. In this study, publicly available expression profiling data from breast cancer and bioinformatics analyses were used to screen potential miRNAs in trastuzumab resistance. A series of gain- or loss-functional assays were performed to define the function of miR-567 and ATG5 in trastuzumab resistance and autophagy, both in vitro and in vivo. Our results showed that miR-567 was significantly decreased in trastuzumab-resistant patients compared with responding patients. Moreover, miR-567 was also downregulated in trastuzumab-resistant cells compared with parental cells. Overexpression of miR-567 reversed chemoresistance, whereas silence of miR-567 induced trastuzumab resistance, both in vitro and in vivo. In addition, enhanced miR-567 could be packaged into exosomes, incorporated into receipt cells, suppressing autophagy and reversed chemoresistance by targeting ATG5. To conclude, exosomal miR-567 plays a key role in reversing trastuzumab resistance via regulating autophagy, indicating it may be a promising therapeutic target and prognostic indicator for breast cancer patients.
A reasonable inflating strategy must be developed for filling an onboard hydrogen storage tank with hydrogen gas. The inflow hydrogen temperature has always been a constant value in filling cases. ...However, in our opinion, the optimal inflow hydrogen temperature is not supposed to be a fixed value but a value that constantly changes and adjusts with filling time, i.e., the inflow hydrogen temperature is a function of the filling time. How to determine this functional relationship is a critical problem to be addressed. Herein, an approach is introduced. A dual-zone model is presented to research the thermal effect during the process of charging hydrogen storage tanks. Based on the numerical results of the dual-zone model, the charging process was divided into three stages, allowing us to obtain data for 1331 filling cases. Then, a back propagation (BP) neural network model was built to analyze the data, and the implicit relationship between the inflow hydrogen temperatures and maximum hydrogen temperature pressure could be deduced. With this implicit relationship, the critical values of the inflow hydrogen temperatures can be obtained from the critical situation. Suppose the inflow hydrogen temperatures in a practical case are higher than the critical values. In that case, the highest hydrogen temperature in the tank will exceed the limited safety value of 358 K. In contrast, if the inflow hydrogen temperatures are lower than the critical values, then more energy will be needed to precool the inlet hydrogen temperature. Thus, theoretically, the critical inflow hydrogen temperatures should be at their optimal values.
The development of biosensors capable of averting biofouling and detecting biomarkers in complex biological media remains a challenge. Herein, an ultralow fouling and highly sensitive biosensor based ...on specifically designed antifouling peptides and a signal amplification strategy was designed for prostate specific antigen (PSA) detection in human serum. A low fouling layer of poly(ethylene glycol) (PEG) doped the conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) was electrodeposited on the electrode surface, followed by the immobilization of streptavidin and further attachment of biotin-labelled peptides. The peptide was designed to include PSA specific recognition domain (HSSKLQK) and antifouling domain (PPPPEKEKEKE), and the terminal of the peptide was functionalized with –SH group. DNA functionalized gold nanorods (DNA/AuNRs) were then attached to the electrode, and methylene blue (MB) molecules were adsorbed to the DNA to form the signal amplifier. In the presence of PSA, the peptide was specifically cleaved and resulted in the loss of AuNRs together with DNA and MB, and thus significant decrease of the current signal. The biosensor exhibited a low limit of detection (LOD) of 0.035 pg mL-1 (S/N = 3), with a wide linear range from 0.10 pg mL-1 to 10.0 ng mL-1, and it was able to detect PSA in real human serum owing to the presence of the antifouling peptides, indicating great potential of the constructed biosensor for practical application.
•An electrochemical antifouling biosensors was prepared based on functional signal amplifier and designed peptides.•The designed peptides exhibited good antifouling and recognizing capabilities.•The DNA functionalized gold nanorods with adsorbed MB can effectively amplify the signal.•The biosensor was able to detect PSA in real human serum samples.
Oxygen vacancies are crucial to the production of reactive oxygen species (ROS) in the metal oxide electrocatalytic membrane (MO x EM) process. Here, using cathodic TiO x EM as a model, we thoroughly ...reveal the roles of oxygen vacancies in ROS generation and transformation. Oxygen vacancies significantly promote H2O2 and •OH production at low concentrations (increment <35%) but inhibit their production at high concentrations (increment >35%). Electrochemical analysis discloses that the enhancement of ROS production profits from the acceleration of charge transfer kinetics by both bulk and surface oxygen vacancies, whereas we attribute the decline in ROS production to the strong adsorption of ROS by surface oxygen vacancies. It is strongly supported by theoretical calculations that reveal the promoted adsorption of *OOH and *OH by oxygen vacancies, which intensifies the capture and scavenging of H2O2 and •OH. Moreover, the gradual increase of interaction time between ROS and oxygen vacancies (from ∼1 to ∼5 s) notably reduces the generation and transformation efficiency of ROS, further highlighting the detrimental impact of oxygen vacancies. In summary, oxygen vacancies show “two faces” toward ROS generation and transformation, acting as ROS promoters at low concentrations but inhibitors at high concentrations. A medium oxygen vacancy concentration is preferred for ROS production, thus causing impressive pollutant removal (>95% removal of bisphenol A within 1.2–1.5 s at 360–440 LMH). This study provides guidance on regulating ROS generation and transformation by manipulating the oxygen vacancy concentration to enhance the decontamination efficiency of MO x EMs.
Ultrasensitive and low-fouling microRNA electrochemical biosensors were successfully constructed by introducing thiol-terminated antifouling molecules (peptide sequence, polyethylene glycol, or ...mercapto alcohol) onto the surface of polyaniline-modified electrodes. For the three kinds of antifouling materials investigated, the newly designed and synthesized peptide exhibited superior antifouling ability to others, and it could effectively reduce the nonspecific adsorption of proteins and even prevent the fouling effect of serum. Compared with microRNA biosensors without antifouling capability, or those modified with polyethylene glycol or mercapto alcohol, the biosensor modified with the designed zwitterionic peptide showed the highest specificity for single-base mismatch, three-base mismatch, and completely complementary microRNAs. Most interestingly, the experimental results indicated that the introduction of antifouling molecules to the sensing interfaces did not significantly change the sensitivity of the biosensor. The strategy of constructing antifouling biosensors based on newly synthesized zwitterionic peptides and conducting polymers can be promisingly extended to the development of other electrochemical sensors and biosensors without encountering biofouling.
Graphical abstract
Ultrasensitive and low-fouling microRNA electrochemical biosensors were constructed by introducing thiol-terminated antifouling molecules (peptide sequence, polyethylene glycol, or mercapto alcohol) onto the surface of polyaniline-modified electrodes. The biosensor modified with the designed zwitterionic peptide showed the highest specificity amongst four kinds of biosensors.
As one specialized subset of regulatory T cells (Tregs), follicular regulatory T cells (TFR) could suppress follicular helper T cells (TFH) and B cells in germinal centers to maintain immune ...homeostasis. The unbalance of TFR and TFH cells could result in abnormal germinal center responses and contribute to pathogenesis of autoimmune diseases. However, the role of TFR cells in systemic lupus erythematosus (SLE) remains unclear. This study revealed a significant increase of CD4+CXCR5+FOXP3+ TFR cells in peripheral blood of SLE patients compared with healthy controls. Meanwhile, the suppression ability of circulating TFR cells was not altered. The ratios of TFR/TFH were increased in SLE patients and the frequency of TFR was positively correlated with auto-antibodies and SLEDAI scores of SLE patients. Our results demonstrated that circulating TFR cells were increased during SLE, which suggested that elevated TFR might be a response to the pathogenesis of SLE to suppress TFH function and may provide novel insight for the pathogenesis of SLE.
•CD4+CXCR5+FoxP3+ TFR cells in the peripheral blood of SLE patients are increased compared with healthy controls.•Ratio of TFR/TFH was significantly elevated in SLE patients.•TFR was positively correlated with auto-antibodies and clinical severity of SLE patients.•Suppressive capacity of circulating TFR cells was not altered in SLE patients.
In order to meet the performance requirements of global optimality and path smoothness in robot path planning, a new fusion algorithm of jump-A * algorithm and dynamic window approach is proposed. ...First, A * algorithm is optimized by using the jump point search method and a new distance evaluation function defined by Manhattan and Euclidean distance to obtain global path information. Then take the dynamic window approach as the core by integrating the global path information to safely plan a global optimal path with high smoothness. The experimental results show that the new fusion algorithm proposed in this paper can not only effectively solve the problem of non-continuous curvature and excessive turning angle at the turning points of the path planned by jump-A * algorithm, but also improve the smoothness of the path and the global optimality. This research is beneficial to the motion control of robots and has certain reference for robot navigation.
Fatty acid and retinol binding proteins (FAR) are unique proteins found in nematodes and are considered potential targets for controlling these parasites. However, their functions in nematode ...parasitism and pathogenicity and interaction with hosts are still unclear. In this study, we investigated the specific roles of rice white tip nematodes (RWTNs), Aphelenchoides besseyi, and a protein, Ab-FAR-1, to elucidate the parasitic and pathogenic processes of nematodes. The results showed that the expression level of Ab-far-1 was significantly up-regulated after A. besseyi infection of the plant. The immunofluorescence and subcellular localisation showed that Ab-FAR-1 was secreted into plant tissues mainly through the body wall of nematodes and might act in the nucleus and cytoplasm of plant cells. The pathogenicity of RWTNs was enhanced in Arabidopsis thaliana overexpressing Ab-FAR-1 and inhibited in Ab-far-1 RNAi A. thaliana. Yeast two-hybrid, Co-IP, BiFC, and nematode inoculation experiments showed that Ab-FAR-1 could interact with the A. thaliana actin-depolymerizing factor protein AtADF3, and the A. thaliana adf3 mutant was more susceptible to nematodes. An in vitro actin filament depolymerisation assay demonstrated that Ab-FAR-1 could inhibit AtADF3-mediated depolymerisation of actin filaments, and the turnover process of cellular actin filaments was also affected in A. thaliana overexpressing Ab-FAR-1. In addition, flg22-mediated host defence responses were suppressed in A. thaliana overexpressing Ab-FAR-1 and adf3 mutants. Therefore, this study confirmed that RWTNs can affect the turnover of actin filament remodelling mediated by AtADF3 through Ab-FAR-1 secretion and thus inhibit plant PAMP-triggered immunity (PTI), promoting the parasitism and pathogenicity of nematodes.
Precise adjustment of the pore size, damage repair, and efficient cleaning is all challenges for the wider application of inorganic membranes. This study reports a simple strategy of combining ...dry‐wet spinning and electrosynthesis to fabricate stainless‐steel metal–organic framework composite membranes characterized by customizable pore sizes, targeted reparability, and high catalytic activity for membrane cleaning. The membrane pore size can be precisely customized in the range of 14–212 nm at nanoscale, and damaged membranes can be repaired by targeted treatment in 120 s. In addition, advanced oxidation processes can be used to quickly clean the membrane and achieve 98% flux recovery. The synergistic actions of the membrane matrix and the selective layer increase the adsorption energy of active sites to oxidant, shorten the electron transfer cycle, and enhance the overall catalytic performance. This study can provide a new direction for the development of advanced membranes for water purification and high‐efficiency membrane cleaning methods.
This study provides a facile protocol for fabricating advanced membranes featuring adjustable pore size, targeted reparability, and high catalytic activity for efficient advanced oxidative processes (AOPs)‐cleaning. The study can serve as a new orientation for the development of advanced membranes for water purification, and also provide sights on a high‐efficiency AOPs membrane cleaning method.
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