Single-molecule analysis reveals the phosphorylation of FLS2 governs its spatiotemporal dynamics and immunity.

The Arabidopsis thaliana FLAGELLIN-SENSITIVE2 (FLS2), a typical receptor kinase, recognizes the conserved 22 amino acid sequence in the N-terminal region of flagellin (flg22) to initiate plant defense pathways, which was intensively studied in the past decades. However, the dynamic regulation of FLS2 phosphorylation at the plasma membrane after flg22 recognition needs further elucidation. Through single-particle tracking, we demonstrated that upon flg22 treatment the phosphorylation of Ser-938 in FLS2 impacts its spatiotemporal dynamics and lifetime. Following Förster resonance energy transfer-fluorescence lifetime imaging microscopy and protein proximity indexes assays revealed that flg22 treatment increased the co-localization of GFP-tagged FLS2/FLS2S938D but not FLS2S938A with AtRem1.3-mCherry, a sterol-rich lipid marker, indicating that the phosphorylation of FLS2S938 affects FLS2 sorting efficiency to AtRem1.3-associated nanodomains. Importantly, we found that the phosphorylation of Ser-938 enhanced flg22-induced FLS2 internalization and immune responses, demonstrating that the phosphorylation may activate flg22-triggered immunity through partitioning FLS2 into functional AtRem1.3-associated nanodomains, which fills the gap between the FLS2S938 phosphorylation and FLS2-mediated immunity.

A high resolution and wide range valve for micronewton cold gas thrusters.

Numerous scientific satellites require micronewton thrusters for compensating environmental disturbances. The mass flow control proportional valve plays a crucial role in precisely regulating the thrust. To meet the high resolution and wide range requirements of the thrusters, this paper introduces a novel proportional valve with two sets of independently controllable piezoelectric stack. One set of the piezo-stack is used to compensate the stroke loss of the valve core, mainly caused by the deformation of the valve seat. The valve sealing mechanism is carefully analyzed to reduce the stroke loss. Another set of the stack works as the primary actuator, enabling the high mass flow control resolution. Two sets of independently controlled piezoelectric stacks not only expand the range and improve the range ratio but also provide redundancy and enhance reliability. This means that the actuator can still operate at lower ranges even if one piezo-stack is damaged. The piezo-actuators are assembled using U-shaped connectors, creating a compact and space-efficient overall design. Experimental tests have been conducted to verify the performance of the valve, which demonstrated a mass flow range of 0-675 µg/s with a resolution better than 0.1 µg/s and a flow noise below 0.1 µg/s/Hz1/2 at 0.1 mHz-1 Hz.

Association between number of dissected lymph nodes and survival in patients undergoing resection for clinical stage IA pure solid lung adenocarcinoma: a retrospective analysis.

BACKGROUND: Lymph node dissection is essential for staging of pure solid lung adenocarcinoma and selection of treatment after surgical resection, particularly for stage I disease since the rate of lymph node metastasis can vary from 0 to 23.7%. METHODS: We retrospectively screened all adult patients (18 years of age or older) who underwent lobectomy for pure solid cT1N0M0 lung adenocarcinoma between January 2015 and December 2017 at our center. Cox proportional hazard regression was used to assess the association between the number of dissected lymph nodes and recurrence-free survival (RFS) and to determine the optimal number of dissected lymph nodes. RESULTS: The final analysis included 458 patients (age: 60.26 ± 8.07 years; 241 women). RFS increased linearly with an increasing number of dissected lymph nodes at a range between 0 and 9. Kaplan-Meier analysis revealed significantly longer RFS in patients with ≥ 9 vs. <9 dissected lymph nodes. In subgroup analysis, ≥ 9 dissected lymph nodes was not only associated with longer RFS in patients without lymph node metastasis (n = 332) but also in patients with metastasis (n = 126). In multivariate Cox proportional hazard regression, ≥ 9 dissected lymph nodes was independently associated with longer RFS (hazard ratio [HR], 0.43; 95% confidence interval [CI], 0.26 to 0.73; P = 0.002). CONCLUSIONS: ≥9 Dissected lymph nodes was associated with longer RFS; accordingly, we recommend dissecting 9 lymph nodes in patients undergoing lobectomy for stage IA pure solid lung adenocarcinoma.

Adjuvant EGFR-TKI therapy in resected EGFR-mutation positive non-small cell lung cancer: A real-world study.

Background: Although several clinical studies have laid the foundation for the adjuvant application of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), some questions remain unresolved. This real-world study aimed to address questions such as the effect of adjuvant chemotherapy prior to adjuvant EGFR-TKI therapy on survival outcomes, and the duration of adjuvant EGFR-TKI therapy, etc. Methods: Between October 2005 and October 2020, 227 consecutive patients with non-small cell lung cancer (NSCLC) who underwent complete pulmonary resections were included in this retrospective study. Patients received postoperative adjuvant chemotherapy followed by EGFR-TKI or adjuvant EGFR-TKI monotherapy. The disease-free survival (DFS) and overall survival (OS) were evaluated. Results: Of the total 227 patients, 55 (24.2%) patients underwent 3-4 cycles of chemotherapy prior to receiving adjuvant EGFR-TKI therapy. The 5-year DFS rate was 67.8%, while the 5-year OS rate was 76.4%. The stages were significantly associated with both DFS (P<0.001) and OS (P<0.001), while no significant differences were observed in the DFS (P=0.093) and OS (P=0.399) between the adjuvant chemotherapy followed by EGFR-TKI and adjuvant EGFR-TKI monotherapy groups. A longer duration of EGFR-TKI therapy was associated with better DFS (P<0.001) and OS (P<0.001) benefit. Additionally, pTNM stage and duration of EGFR-TKI therapy were considered independent prognostic factors for long-term survival (All P<0.05). Conclusions: This study supports the use of EGFR-TKI as a postoperative adjuvant treatment for patients with stage II-IIIA EGFR-mutation positive NSCLC. Additionally, patients with stage I who had pathological risk factors were also suitable for receiving adjuvant EGFR-TKI therapy. Postoperative EGFR-TKI based, chemotherapy-free adjuvant regimen may be a potential therapeutic option for patients with EGFR-mutation positive NSCLC.