The presumable effects of hydroxychloroquine and its metabolites in the treatment of systemic lupus erythematosus.

OBJECTIVE: Hydroxychloroquine (HCQ) is an essential drug in the treatment of systemic lupus erythematosus (SLE). This study aimed to detect the concentrations of HCQ and its metabolites from peripheral blood of SLE patients and to investigate the relationship between those concentrations and SLE disease activity. METHODS: 176 SLE patients treated with HCQ were enrolled in this study. The concentrations of HCQ and its metabolites in their peripheral blood were measured by high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). Patients' disease activity was evaluated with the systemic lupus erythematosus disease activity index (SLEDAI). The variables between different concentrations or treatments were statistically analyzed. Linear regression was employed to explore relationships between the concentrations of HCQ and its metabolites with the disease activity. RESULTS: The SLEDAI was lower in patients with higher concentrations of HCQ, desethylhydroxychloroquine (DHCQ), and desethylchloroquine (DCQ) (P = 0.024, P = 0.018, and P = 0.003, respectively). There were no significant differences in SLEDAI and the concentrations of HCQ and its metabolites among groups with different treatments (P > 0.05). After adjusting age, gender, disease duration, HCQ dose adjusted to actual body weight, and glucocorticoid (GC) dose, the SLEDAI was negatively correlated with the concentrations of HCQ, DHCQ, DCQ and bisdesethylchloroquine (BDCQ) (P = 0.007, P = 0.011, P = 0.029, and P = 0.008, respectively). After grouping analysis, in patients treated with HCQ and GC, the SLEDAI was negatively correlated with concentrations of HCQ, DHCQ and BDCQ (P = 0.011, P = 0.035, and P = 0.036, respectively). CONCLUSIONS: The concentrations of HCQ and metabolites were correlated with the SLE disease activity after adjusting possible confounding factors, indicating that HCQ and its metabolites might play certain immunoregulatory roles in SLE treatment. Moreover, GC might have a synergistic effect with HCQ. It is helpful in clinical management and follow-up to monitor the concentrations of HCQ and its metabolites in SLE patients.

Study on diversity, nitrogen-fixing capacity, and heavy metal tolerance of culturable Pongamia pinnata rhizobia in the vanadium-titanium magnetite tailings.

Introduction: The diversity, nitrogen-fixing capacity and heavy metal tolerance of culturable rhizobia in symbiotic relationship with Pongamia pinnata surviving in vanadium (V) - titanium (Ti) magnetite (VTM) tailings is still unknown, and the rhizobia isolates from the extreme barren VTM tailings contaminated with a variety of metals would provide available rhizobia resources for bioremediation. Methods: P. pinnata plants were cultivated in pots containing the VTM tailings until root nodules formed, and then culturable rhizobia were isolated from root nodules. The diversity, nitrogen-fixing capacity and heavy metal tolerance of rhizobia were performed. Results: Among 57 rhizobia isolated from these nodules, only twenty strains showed different levels of tolerance to copper (Cu), nickel (Ni), manganese (Mn) and zinc (Zn), especially strains PP1 and PP76 showing high tolerance against these four heavy metals. Based on the phylogenetic analysis of 16S rRNA and four house-keeping genes (atpD, recA, rpoB, glnII), twelve isolates were identified as Bradyrhizobium pachyrhizi, four as Ochrobactrum anthropic, three as Rhizobium selenitireducens and one as Rhizobium pisi. Some rhizobia isolates showed a high nitrogen-fixing capacity and promoted P. pinnata growth by increasing nitrogen content by 10%-145% in aboveground plant part and 13%-79% in the root. R. pachyrhizi PP1 showed the strongest capacity of nitrogen fixation, plant growth promotion and resistance to heavy metals, which provided effective rhizobia strains for bioremediation of VTM tailings or other contaminated soils. This study demonstrated that there are at least three genera of culturable rhizobia in symbiosis with P. pinnata in VTM tailings. Discussion: Abundant culturable rhizobia with the capacity of nitrogen fixation, plant growth promotion and resistance to heavy metals survived in VTM tailings, indicating more valuable functional microbes could be isolated from extreme soil environments such as VTM tailings.

Targeting immune checkpoints in anti-neutrophil cytoplasmic antibodies associated vasculitis: the potential therapeutic targets in the future.

Anti-neutrophil cytoplasmic autoantibodies (ANCA) associated vasculitis (AAV) is a necrotizing vasculitis mainly involving small blood vessels. It is demonstrated that T cells are important in the pathogenesis of AAV, including regulatory T cells (Treg) and helper T cells (Th), especially Th2, Th17, and follicular Th cells (Tfh). In addition, the exhaustion of T cells predicted the favorable prognosis of AAV. The immune checkpoints (ICs) consist of a group of co-stimulatory and co-inhibitory molecules expressed on the surface of T cells, which maintains a balance between the activation and exhaustion of T cells. CD28, inducible T-cell co-stimulator (ICOS), OX40, CD40L, glucocorticoid induced tumor necrosis factor receptor (GITR), and CD137 are the common co-stimulatory molecules, while the programmed cell death 1 (PD-1), cytotoxic T lymphocyte-associated molecule 4 (CTLA-4), T cell immunoglobulin (Ig) and mucin domain-containing protein 3 (TIM-3), B and T lymphocyte attenuator (BTLA), V-domain Ig suppressor of T cell activation (VISTA), T-cell Ig and ITIM domain (TIGIT), CD200, and lymphocyte activation gene 3 (LAG-3) belong to co-inhibitory molecules. If this balance was disrupted and the activation of T cells was increased, autoimmune diseases (AIDs) might be induced. Even in the treatment of malignant tumors, activation of T cells by immune checkpoint inhibitors (ICIs) may result in AIDs known as rheumatic immune-related adverse events (Rh-irAEs), suggesting the importance of ICs in AIDs. In this review, we summarized the features of AAV induced by immunotherapy using ICIs in patients with malignant tumors, and then reviewed the biological characteristics of different ICs. Our aim was to explore potential targets in ICs for future treatment of AAV.

Satellite Navigation Spoofing Interference Detection and Direction Finding Based on Array Antenna.

Satellite navigation signals are feeble when they reach the ground, so they are vulnerable to attacks from outside interference signals. By emitting spoofing interference signals similar to real satellite signals, spoofing interference can make receivers give wrong navigation, position, and time information, and it is challenging to detect. This seriously affects the safe use of GNSS; therefore, it is essential to identify spoofing interference signals quickly and accurately. In our study, we proposed a novel six-array spoofing-interference-monitoring array antenna, which achieved the detection and identification of spoofing interference sources by monitoring the relevant peaks and combining an airspace-trapping algorithm. Moreover, we quickly accomplished our search for the whole circumferential ambiguity by using long- and short-baseline algorithms, which can realize the high-precision detection of spoofing interference sources. To verify this method's accuracy, we conducted outdoor real experiments using a special spoofing interference source, and our experimental results show that our proposed array antenna's directional accuracy for spoofing interference signals is kept within 2°, showing high spoofing interference direction-finding capability.

Neutrophils in ANCA-associated vasculitis: Mechanisms and implications for management.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of systemic autoimmune diseases, which is typified by inflammatory necrosis predominantly affecting the small vessels and often accompanied by positive ANCA. Clinically, AAV primarily includes microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic granulomatosis with polyangiitis (EGPA). It has been found that in AAV pathogenesis, both innate and adaptive immunity are related to neutrophil function mutually. Many proteins, such as myeloperoxidase (MPO) and proteinase 3 (PR3), in neutrophil cytoplasm lead to the production of proteins such as MPO-ANCA and PR3-ANCA by activating adaptive immunity. In addition, through the process of neutrophil extracellular trap (NET) formation, activation of an alternative complement pathway and the respiratory burst can stimulate the neutrophils close to vascular endothelial cells and will participate the vessel inflammation. This review aims to reveal the potential mechanisms regulating the association between the neutrophils and various types of AAVs and to emphasize the results of recent findings on these interactions. Moreover, multiple underlying signaling pathways involved in the regulation of neutrophils during AAV processes have also been discussed. The ultimate goal of this review is to identify novel biomarkers and therapeutic targets for AAV management in the future.