Rhizobial-induced phosphatase GmPP2C61A positively regulates soybean nodulation.

Symbiotic nitrogen fixation (SNF) is crucial for legumes, providing them with the nitrogen necessary for plant growth and development. Nodulation is the first step in the establishment of SNF. However, the determinant genes in soybean nodulation and the understanding of the underlying molecular mechanisms governing nodulation are still limited. Herein, we identified a phosphatase, GmPP2C61A, which was specifically induced by rhizobia inoculation. Using transgenic hairy roots harboring GmPP2C61A::GUS, we showed that GmPP2C61A was mainly induced in epidermal cells following rhizobia inoculation. Functional analysis revealed that knockdown or knock-out of GmPP2C61A significantly reduced the number of nodules, while overexpression of GmPP2C61A promoted nodule formation. Additionally, GmPP2C61A protein was mainly localized in the cytoplasm and exhibited conserved phosphatase activity in vitro. Our findings suggest that phosphatase GmPP2C61A serves as a critical regulator in soybean nodulation, highlighting its potential significance in enhancing symbiotic nitrogen fixation.

Tumor-associated neutrophils and macrophages exacerbate antidrug IgG-mediated anaphylactic reaction against an immune checkpoint inhibitor.

BACKGROUND: With the increased use of immune checkpoint inhibitors (ICIs), side effects and toxicity are a great concern. Anaphylaxis has been identified as a potential adverse event induced by ICIs. Anaphylaxis is a life-threatening medical emergency. However, the mechanisms and factors that can potentially influence the incidence and severity of anaphylaxis in patients with cancer remain unclear. METHODS: Healthy, murine colon 26, CT26, breast 4T1, EMT6, and renal RENCA tumor-bearing mice were treated with an anti-PD-L1 antibody (clone 10F.9G2). Symptoms of anaphylaxis were evaluated along with body temperature and mortality. The amounts of antidrug antibody and platelet-activating factor (PAF) in the blood were quantified via ELISA and liquid chromatography-mass spectrometry (LC-MS/MS). Immune cells were analyzed and isolated using a flow cytometer and magnetic-activated cell sorting, respectively. RESULTS: Repeated administration of the anti-PD-L1 antibody 10F.9G2 to tumor-bearing mice caused fatal anaphylaxis, depending on the type of tumor model. After administration, antidrug immunoglobulin G (IgG), but not IgE antibodies, were produced, and PAF was released as a chemical mediator during anaphylaxis, indicating that anaphylaxis was caused by an IgG-dependent pathway. Anaphylaxis induced by 10F.9G2 was treated with a PAF receptor antagonist. We identified that neutrophils and macrophages were PAF-producing effector cells during anaphylaxis, and the tumor-bearing models with increased numbers of neutrophils and macrophages showed lethal anaphylaxis after treatment with 10F.9G2. Depletion of both neutrophils and macrophages using clodronate liposomes prevented anaphylaxis in tumor-bearing mice. CONCLUSIONS: Thus, increased numbers of neutrophils and macrophages associated with cancer progression may be risk factors for anaphylaxis. These findings may provide useful insights into the mechanism of anaphylaxis following the administration of immune checkpoint inhibitors in human subjects.

Risk factors for sub-therapeutic serum concentrations of magnesium sulfate in severe preeclampsia of Chinese patients.

BACKGROUND: Magnesium sulfate (MgSO4) is the standard drug for eclampsia prophylaxis and treatment. In China, the effective therapeutic serum magnesium level is 1.8-3.0 mmol/L. There is little information on how to achieve and maintain effective therapeutic concentrations. This study aimed to investigate risk factors for sub-therapeutic serum concentrations of MgSO4 in patients with severe preeclampsia. METHODS: Patients with severe preeclampsia who received MgSO4 intravenous infusion were retrospectively reviewed. The maternal demographic characteristics, regimens for the administration of MgSO4, and lab test results of patients were collected. Multivariate logistic regression analysis and receiver operating characteristic (ROC) curve analysis were conducted for the risk factors influencing the serum magnesium concentration. RESULTS: A total of 93 patients with severe preeclampsia were included in the study. 52 (55.91%) patients did not attain therapeutic serum magnesium levels. A multivariate logistic regression analysis identified creatinine clearance (Ccr), whether the loading dose was given, and measurement time of serum magnesium concentration (referring to the time from start of MgSO4 infusion to blood draw for serum sampling) as independent risk factors for sub-therapeutic serum magnesium concentration (P < 0.05). ROC curve analysis indicated that the continuous variable Ccr had a significant predictive value for the serum magnesium concentration, which resulted in a cutoff point of 133 mL/min; while measurement time had limited predictive value, with cutoff point of 2.375 h. CONCLUSIONS: Ccr, whether the loading dose was given, and measurement time were independent risk factors for sub-therapeutic serum magnesium concentration. A loading dose of MgSO4 everytime before the maintenance dose, as well as the duration of MgSO4 maintenance dose of more than 2.375 h are recommended for all the patients with severe PE. Routine evaluation of serum magnesium levels is a recommended practice for women with severe PE and whose Ccr is ≥133 mL/min.