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Introduction: Our aim in this study was to identify the prevalence and clinical characteristics of LRP4/agrin-antibody-positive double-seronegative myasthenia gravis (DNMG).Methods: DNMG patients at 16 sites in the United States were tested for LRP4 and agrin antibodies, and the clinical data were collected.Results: Of 181 DNMG patients, 27 (14.9%) were positive for either low-density lipoprotein receptor-related protein 4 (LRP4) or agrin antibodies. Twenty-three DNMG patients (12.7%) were positive for both antibodies. More antibody-positive patients presented with generalized symptoms (69%) compared with antibody-negative patients (43%) (P ≤ .02). Antibody-positive patients' maximum classification on the Myasthenia Gravis Foundation of America (MGFA) scale was significantly higher than that for antibody-negative patients (P ≤ .005). Seventy percent of antibody-positive patients were classified as MGFA class III, IV, or V compared with 39% of antibody-negative patients. Most LRP4- and agrin-antibody-positive patients (24 of 27, 89%) developed generalized myathenia gravis (MG), but with standard MG treatment 81.5% (22 of 27) improved to MGFA class I or II during a mean follow-up of 11 years.Discussion: Antibody-positive patients had more severe clinical disease than antibody-negative patients. Most DNMG patients responded to standard therapy regardless of antibody status. [ABSTRACT FROM AUTHOR]

Based on environmental monitoring data and meteorological observation data from 2016 to 2022 in Beijing, combined with backward trajectory clustering and potential source area contribution analysis, the characteristics, meteorological impacts, and potential source areas of ozone (O 3 ) pollution were analyzed. The results showed that there was a total of 41 O 3 pollution processes with jumping characteristics in Beijing from 2016 to 2022, with an average of 5.9 times a year. The occurrence time was concentrated in May to July, and the day of the jump (OJD2) was higher than the day before the jump (OJD1). The average value of ρ (O 3 -8h) was 78.3% higher, and the peak concentration was 78.9% higher. The high O 3 concentration zone in the OJD2 region exhibited a characteristic of advancing from south to north. The main reasons for the occurrence of jumped O 3 pollution in Beijing could be summarized as local accumulation caused by unfavorable meteorological conditions and regional transmission impact. The occurrence of jump-type ozone pollution was characterized by an increase in southerly wind frequency, temperature rise, pressure decrease, and precipitation decrease. The increase in southerly wind frequency provided conditions for the transport of O 3 and its precursors, and rapid photochemical reactions occurred under local high temperatures, with less superimposed precipitation, comprehensively pushing up the ozone concentration level of OJD2. Six air mass transporting pathways were identified through clustering analysis; the air mass from the direction north of OJD2 decreased by 11.2%, whereas the air mass from the south and east directions increased by 6.7% and 4.4%, respectively, with the air masses mainly transmitting over short distances. The ozone concentration corresponding to the south and east directions was relatively high, making a significant contribution to Beijing's pollution. The analysis of potential source areas revealed that the main potential source areas of OJD2 ozone pollution were the central, southern, and eastern parts of Beijing-Tianjin-Hebei, which contributed 82.6% to the pollution trajectory. There was a significant contribution of regional transport during jump-type ozone pollution, and it is necessary to strengthen joint prevention and control in the Beijing-Tianjin-Hebei Region.

O 3 continuous monitoring data for the Dingling, Guanyuan, Liulihe, and Qianmen sites from 2006-2015 were analyzed to investigate concentration levels, variation trends, temporal variations, and relationships with precursors and meteorological factors. The results showed that the ten year average concentrations of O 3 at the Dingling site were the highest at 65.2 μg·m -3 , followed by concentrations at Liulihe (53.4 μg·m -3 ), Guanyuan (49.6 μg·m -3 ) and Qianmen (40.4 μg·m -3 ). The O 3 concentrations at Dingling showed a decreasing trend[0.5 μg·(m 3 ·a) -1 ], while O 3 concentrations at Guanyuan[0.9 μg·(m 3 ·a) -1 ], Liulihe[0.3 μg·(m 3 ·a) -1 ], and Qianmen[0.3 μg·(m 3 ·a) -1 ] showed an increasing trend. The highest monthly average concentrations appeared during June and August, and the highest frequency occurred in July (17 times) with average concentrations of 99.8 μg·m -3 . The lowest monthly average concentrations appeared during November and February, and the highest frequency occurred in January (14 times) with an average concentration of 16.6 μg·m -3 . Notably, the time for the peak concentrations of O 3 appeared earlier in the day in recent years. The peak concentrations of O 3 appeared at 15:00-16:00 during 2013-2015, which was 1-2 hours earlier than previous years. The heavy air pollution of O 3 occurred on 11 days at the Dingling site in 2015, which was ten days more than in 2013, indicating O 3 pollution in the downwind suburban regions of Beijing in summer became more and more serious. The concentrations of O 3 and NO 2 at Dingling showed a positive correlation, while the concentrations of O 3 and NO 2 at the other sites showed a negative correlation, indicating O 3 formation in Dingling was sensitive to NO 2 chemistry, while O 3 formation at the other sites was sensitive to VOC chemistry. The concentrations of O 3 showed a positive correlation with temperature and negative correlations with humidity and surface pressure. Temperature had the greatest influence on O 3 concentration, followed by surface pressure and humidity. For cases when daily maximum temperature exceeded 30℃ and relative humidity was between 30% and 70%, the probability of the O 3 daily maximum 8 h concentration exceeding 200 μg·m -3 was high, indicating the air quality level reached levels for light pollution and moderate pollution.

Bone homeostasis depends on the functional balance of osteoblasts (OBs) and osteoclasts (OCs). Lrp4 is a transmembrane protein that is mutated in patients with high bone mass. Loss of Lrp4 in OB-lineage cells increases bone mass by elevating bone formation by OBs and reducing bone resorption by OCs. However, it is unclear how Lrp4 deficiency in OBs impairs osteoclastogenesis. Here, we provide evidence that loss of Lrp4 in the OB lineage stabilizes the prorenin receptor (PRR) and increases PRR/V-ATPase-driven ATP release, thereby enhancing the production of the ATP derivative adenosine. Both pharmacological and genetic inhibition of adenosine- 2A receptor (A 2A R) in culture and Lrp4 mutant mice diminishes the osteoclastogenic deficit and reduces trabecular bone mass. Furthermore, elevated adenosine-A 2A R signaling reduces receptor activator of nuclear factor κB (RANK)-mediated osteoclastogenesis. Collectively, these results identify a mechanism by which osteoblastic Lrp4 controls osteoclastogenesis, reveal a cross talk between A 2A R and RANK signaling in osteoclastogenesis, and uncover an unrecognized pathophysiological mechanism of high-bone-mass disorders., (© 2017 Xiong et al.)