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Ammonium transporter (AMT)-mediated acquisition of ammonium nitrogen from soils is essential for the nitrogen demand of plants, especially for those plants growing in flooded or acidic soils where ammonium is dominant. Recent advances show that AMTs additionally participate in many other physiological processes such as transporting ammonium from symbiotic fungi to plants, transporting ammonium from roots to shoots, transferring ammonium in leaves and reproductive organs, or facilitating resistance to plant diseases via ammonium transport. Besides being a transporter, several AMTs are required for the root development upon ammonium exposure. To avoid the adverse effects of inadequate or excessive intake of ammonium nitrogen on plant growth and development, activities of AMTs are fine-tuned not only at the transcriptional level by the participation of at least four transcription factors, but also at protein level by phosphorylation, pH, endocytosis, and heterotrimerization. Despite these progresses, it is worth noting that stronger growth inhibition, not facilitation, unfortunately occurs when AMT overexpression lines are exposed to optimal or slightly excessive ammonium. This implies that a long road remains towards overcoming potential limiting factors and achieving AMT-facilitated yield increase to accomplish the goal of persistent yield increase under the present high nitrogen input mode in agriculture.

ContextCushing disease (CD) due to adrenocorticotropic hormone–secreting pituitary tumors can be a management challenge.ObjectiveTo better understand the outcomes of stereotactic radiosurgery (SRS) for CD and define its role in management.DesignInternational, multicenter, retrospective cohort analysis.SettingTen medical centers participating in the International Gamma Knife Research Foundation.PatientsPatients with CD with >6 months endocrine follow-up.InterventionSRS using Gamma Knife radiosurgery.Main Outcome MeasuresThe primary outcome was control of hypercortisolism (defined as normalization of free urinary cortisol). Radiologic response and adverse radiation effects (AREs) were recorded.ResultsIn total, 278 patients met inclusion criteria, with a mean follow-up of 5.6 years (0.5 to 20.5 years). Twenty-two patients received SRS as a primary treatment of CD. Mean margin dose was 23.7 Gy. Cumulative initial control of hypercortisolism was 80% at 10 years. Mean time to cortisol normalization was 14.5 months. Recurrences occurred in 18% with initial cortisol normalization. Overall, the rate of durable control of hypercortisolism was 64% at 10 years and 68% among patients who received SRS as a primary treatment. AREs included hypopituitarism (25%) and cranial neuropathy (3%). Visual deficits were related to treatment of tumor within the suprasellar cistern (P = 0.01), whereas both visual (P < 0.0001) and nonvisual cranial neuropathy (P = 0.02) were related to prior pituitary irradiation.ConclusionsSRS for CD is well tolerated and frequently results in control of hypercortisolism. However, recurrences can occur. SRS should be considered for patients with persistent hypercortisolism after pituitary surgery and as a primary treatment in those unfit for surgery. Long-term endocrine follow-up is essential after SRS.We studied the outcomes of stereotactic radiosurgery for Cushing disease in 278 patients and found that this treatment can result in durable endocrine remission in appropriately selected patients.

Background The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, also called 2019-nCoV) causes different morbidity risks to individuals in different age groups. This study attempts to quantify the age-specific transmissibility using a mathematical model. Methods An epidemiological model with five compartments (susceptible–exposed–symptomatic–asymptomatic–recovered/removed [SEIAR]) was developed based on observed transmission features. Coronavirus disease 2019 (COVID-19) cases were divided into four age groups: group 1, those ≤ 14 years old; group 2, those 15 to 44 years old; group 3, those 45 to 64 years old; and group 4, those ≥ 65 years old. The model was initially based on cases (including imported cases and secondary cases) collected in Hunan Province from January 5 to February 19, 2020. Another dataset, from Jilin Province, was used to test the model. Results The age-specific SEIAR model fitted the data well in each age group ( P  < 0.001). In Hunan Province, the highest transmissibility was from age group 4 to 3 (median: β 43  = 7.71 × 10 − 9 ; SAR 43  = 3.86 × 10 − 8 ), followed by group 3 to 4 (median: β 34  = 3.07 × 10 − 9 ; SAR 34  = 1.53 × 10 − 8 ), group 2 to 2 (median: β 22  = 1.24 × 10 − 9 ; SAR 22  = 6.21 × 10 − 9 ), and group 3 to 1 (median: β 31  = 4.10 × 10 − 10 ; SAR 31  = 2.08 × 10 − 9 ). The lowest transmissibility was from age group 3 to 3 (median: β 33  = 1.64 × 10 − 19 ; SAR 33  = 8.19 × 10 − 19 ), followed by group 4 to 4 (median: β 44  = 3.66 × 10 − 17 ; SAR 44  = 1.83 × 10 − 16 ), group 3 to 2 (median: β 32  = 1.21 × 10 − 16 ; SAR 32  = 6.06 × 10 − 16 ), and group 1 to 4 (median: β 14  = 7.20 × 10 − 14 ; SAR 14  = 3.60 × 10 − 13 ). In Jilin Province, the highest transmissibility occurred from age group 4 to 4 (median: β 43  = 4.27 × 10 − 8 ; SAR 43  = 2.13 × 10 − 7 ), followed by group 3 to 4 (median: β 34  = 1.81 × 10 − 8 ; SAR 34  = 9.03 × 10 − 8 ). Conclusions SARS-CoV-2 exhibits high transmissibility between middle-aged (45 to 64 years old) and elderly (≥ 65 years old) people. Children (≤ 14 years old) have very low susceptibility to COVID-19. This study will improve our understanding of the transmission feature of SARS-CoV-2 in different age groups and suggest the most prevention measures should be applied to middle-aged and elderly people.

Background Catheter ablation (CA) is currently used to treat persistent atrial fibrillation (PeAF). However, its effectiveness is limited. This study aimed to estimate the effectiveness of the vein of Marshall absolute ethanol injection (VOM‐EI) for PeAF ablation. Hypothesis Adjunctive vein of Marshall ethanol injection (VOM‐EI) strategies are more effective than conventional catheter ablation (CA) and have similar safety outcomes. Methods We extensively searched the literature for studies evaluating the effectiveness and safety of VOM‐EI + CA compared with CA alone. The primary endpoint was the rate of acute bidirectional block of the isthmus of the mitral annulus (MIBB). The secondary endpoints were atrial fibrillation (AF) or atrial tachycardia (AT) recurrence over 30 seconds after a 3‐month blanking period. Weighted pooled risk ratios (RRs) and corresponding 95% confidence intervals (CIs) were calculated using a random effects model. Results Based on the selection criteria, nine studies were included in this systematic review, including patients with AF (n = 2508), persistent AF (n = 1829), perimitral flutter (n = 103), and perimitral AT (n = 165). There were 1028 patients in the VOM‐EI + CA group and 1605 in the CA alone group. The VOM‐EI + CA group showed a lower rate of AF/AT relapse (RR = 0.70; 95% CI = 0.53–0.91; p = .008) and a higher rate of acute MIBB (RR = 1.29; 95% CI = 1.11–1.50; p = .0007) than the CA alone group. Conclusion Our meta‐analysis revealed that adjunctive VOM‐EI strategies are more effective than conventional CA and have similar safety outcomes. Efficacy and feasibility of vein of Marshall ethanol infusion. Through literature search and meta‐analysis, it was found that adjunctive vein of Marshall ethanol injection (VOM‐EI) strategies are more effective than conventional catheter ablation (CA) and have similar safety outcomes.

The geographic origin and migration of the brown rat (Rattus norvegicus) remain subjects of considerable debate. In this study, we sequenced whole genomes of 110 wild brown rats with a diverse world-wide representation. We reveal that brown rats migrated out of southern East Asia, rather than northern Asia as formerly suggested, into the Middle East and then to Europe and Africa, thousands of years ago. Comparison of genomes from different geographical populations reveals that many genes involved in the immune system experienced positive selection in the wild brown rat.

Background Post cardiac injury syndrome (PCIS) is induced by myocardial infarction or cardiac surgery, as well as minor insults to the heart such as percutaneous coronary intervention (PCI), or insertion of a pacing lead. PCIS is characterized by pericarditis after injury to the heart. The relatively low incidence makes differential diagnosis of PCIS after PCI or implantation of a pacemaker a challenge. This report describes two typical cases of PCIS. Case presentation The first patient presented with signs of progressive cardiac tamponade that occurred two weeks after implantation of a permanent pacemaker. Echocardiography confirmed the presence of a moderate amount of newly-formed pericardial effusion. The second patient underwent PCI for the right coronary artery. However, despite an uneventful procedure, the patient experienced dyspnea, tightness of chest and cold sweats, and bradycardia two hours after the procedure. Echocardiography findings, which showed a moderate amount of newly-formed pericardial effusion, suggested acute cardiac tamponade, and compromised hemodynamics. Both patients recovered with medication. Conclusion These cases illustrated that PCIS can occur after minor myocardial injury, and that the possibility of PCIS should be considered if there is a history of possible cardiac insult.

Maize grows in nitrate-dominated dryland soils, but shortly upon localized dressing of nitrogen fertilizers, ammonium is retained as a noticeable form of nitrogen source available to roots. Thus in addition to nitrate, the absorption of ammonium can be an important strategy that promotes rapid plant growth at strong nitrogen demanding stages. The present study reports the functional characterization of three root-expressed ammonium transporters (AMTs), aiming at finding out functional and regulatory properties that correlate with efficient nitrogen acquisition of maize. Using a stable electrophysiological recording method we previously established in Xenopus laevis oocytes that integrates the capture of currents in response to voltage ramps with onsite stability controls, we demonstrate that all three ZmAMT1s engage NH4+ uniporting as ammonium uptake mechanisms. The K m value for ZmAMT1.1a, 1.1b, or ZmAMT1.3 is, respectively, 9.9, 15.6, or 18.6 μM, indicating a typical high-affinity transport of NH4+ ions. Importantly, the uptake currents of these ZmAMT1s are markedly amplified upon extracellular acidification. A pH drop from 7.4 to 5.4 results in a 140.8%, 64.1% or a 120.7% increase of ammonium uptake activity through ZmAMT1.1a, 1.1b, or ZmAMT1.3. Since ammonium uptake by plant roots accompanies a spontaneous acidification to the root medium, the functional promotion of ZmAMT1.1a, 1.1b, and ZmAMT1.3 by low pH is in line with the facilitated ammonium uptake activity in maize roots. Furthermore, the expression of the three ZmAMT1 genes is induced under ammonium-dominated conditions. Thus we describe a facilitated ammonium uptake strategy in maize roots by functional and expression regulations of ZmAMT1 transporters that may coordinate with efficient acquisition of this form of nitrogen source when available.

Abstract BACKGROUND Stereotactic radiosurgery (SRS) is a potentially important option for intracranial ependymoma patients. OBJECTIVE To analyze the outcomes of intracranial ependymoma patients who underwent SRS as a part of multimodality management. METHODS Seven centers participating in the International Gamma Knife Research Foundation identified 89 intracranial ependymoma patients who underwent SRS (113 tumors). The median patient age was 16.3 yr (2.9-80). All patients underwent previous surgical resection and radiation therapy (RT) of their ependymomas and 40 underwent previous chemotherapy. Grade 2 ependymomas were present in 42 patients (52 tumors) and grade 3 ependymomas in 48 patients (61 tumors). The median tumor volume was 2.2 cc (0.03-36.8) and the median margin dose was 15 Gy (9-24). RESULTS Forty-seven (53%) patients were alive and 42 (47%) patients died at the last follow-up. The overall survival after SRS was 86% at 1 yr, 50% at 3 yr, and 44% at 5 yr. Smaller total tumor volume was associated with longer overall survival (P = .006). Twenty-two patients (grade 2: n = 9, grade 3: n = 13) developed additional recurrent ependymomas in the craniospinal axis. The progression-free survival after SRS was 71% at 1 yr, 56% at 3 yr, and 48% at 5 yr. Adult age, female sex, and smaller tumor volume indicated significantly better progression-free survival. Symptomatic adverse radiation effects were seen in 7 patients (8%). CONCLUSION SRS provides another management option for residual or recurrent progressive intracranial ependymoma patients who have failed initial surgery and RT.

ObjectiveTo investigate the outcomes of cerebrospinal fluid (CSF) diversion in lung cancer patients with leptomeningeal carcinomatosis (LMC).MethodsA retrospective review of consecutive lung cancer patients with LMC suffering from increased intracranial pressure (IICP) and hydrocephalus between February 2017 and February 2020. We evaluated the survival benefit of CSF diversion surgery and assessed the outcomes of treatments administered post-LMC in terms of overall survival and shunt-related complications.ResultsThe study cohort included 50 patients (median age: 59 years). Ventricular peritoneal (VP) shunts were placed in 33 patients, and lumbar peritoneal (LP) shunts were placed in 7 patients. Programmable shunts were placed in 36 patients. Shunt adjustment was performed in 19 patients. Kaplan-Meier analysis revealed that shunt placement increased overall survival from 1.95 months to 6.21 months (p = 0.0012) and increased Karnofsky Performance Scores (KPS) from 60 to 70. Univariate analysis revealed no difference between VP or LP shunts in terms of survival. No differences in post-shunt systemic treatments (tyrosine kinase inhibitors (TKIs) or systemic treatments) were observed in overall survival. Shunt-related complications were noted in 7 patients, including shunt obstruction (n = 4), infection (n = 1), and over-drainage (n = 2).ConclusionCSF diversion (VP or LP shunt) appears to be an effective and safe treatment for lung cancer patients with LMC and hydrocephalus. Programmable shunts should be considered for complex cases, which commonly require pressure adjustments as the disease progresses.

AtAMT1;3 is a major contributor to high-affinity ammonium uptake in Arabidopsis roots. Using a stable electrophysiological recording strategy, we demonstrate in Xenopus laevis oocytes that AtAMT1;3 functions as a typical high-affinity NH4+ uniporter independent of protons and Ca2+. The findings that AtAMT1;3 transports methylammonium (MeA+, a chemical analog of NH4+) with extremely low affinity ( K m in the range of 2.9–6.1 mM) led to investigate the mechanisms underlying substrate binding. Homologous modeling and substrate docking analyses predicted that the deduced substrate binding motif of AtAMT1;3 facilitates the binding of NH4+ ions but loosely accommodates the binding of MeA+ to a more superficial location of the permeation pathway. Amongst point mutations tested based on this analysis, P181A resulted in both significantly increased current amplitudes and substrate binding affinity, whereas F178I led to opposite effects. Thus these 2 residues, which flank W179, a major structural component of the binding site, are also important determinants of AtAMT1;3 transport capacity by being involved in substrate binding. The Q365K mutation neighboring the histidine residue H378, which confines the substrate permeation tunnel, affected only the current amplitudes but not the binding affinities, providing evidence that Q365 mainly controls the substrate diffusion rate within the permeation pathway.