Explore the vast range of titles available.

Osmotic stress severely inhibits plant growth and development, causing huge loss of crop quality and quantity worldwide. Melatonin is an important signaling molecule that generally confers plant increased tolerance to various environmental stresses, however, whether and how melatonin participates in plant osmotic stress response remain elusive. Here, we report that melatonin enhances plant osmotic stress tolerance through increasing ROS-scavenging ability, and melatonin receptor CAND2 plays a key role in melatonin-mediated plant response to osmotic stress. Upon osmotic stress treatment, the expression of melatonin biosynthetic genes including SNAT1, COMT1, and ASMT1 and the accumulation of melatonin are increased in the wild-type plants. The snat1 mutant is defective in osmotic stress-induced melatonin accumulation and thus sensitive to osmotic stress, while exogenous melatonin enhances the tolerance of the wild-type plant and rescues the sensitivity of the snat1 mutant to osmotic stress by upregulating the expression and activity of catalase and superoxide dismutase to repress H2O2 accumulation. Further study showed that the melatonin receptor mutant cand2 exhibits reduced osmotic stress tolerance with increased ROS accumulation, but exogenous melatonin cannot revert its osmotic stress phenotype. Together, our study reveals that CADN2 functions necessarily in melatonin-conferred osmotic stress tolerance by activating ROS-scavenging ability in Arabidopsis.

There is limited evidence concerning real-world efficacy of second-line (2L) treatment with immune checkpoint inhibitors (ICIs) in extensive-stage small-cell lung cancer (ES-SCLC). In this study, we evaluated the efficacy of 2L-ICIs therapy in patients with ES-SCLC. In this retrospective study, we included patients with ES-SCLC who experienced disease progression following first-line (1L) therapy and received 2L treatment between March 2019 and December 2023. The primary endpoint of this study was progression-free survival (PFS), and the secondary endpoints included safety, the objective response rate (ORR), the disease control rate (DCR), and overall survival (OS). Survival analyses were conducted using Kaplan-Meier curves. One-to-one propensity score matching (PSM) was used to reduce confounding. Univariate and multivariate Cox regression analyses were conducted to identify factors associated with PFS and OS. We included 496 patients in this study; among them, 200 patients were in the 2L-ICIs group and 296 patients were in the 2L-non-ICIs group. The 2L-ICIs group demonstrated significantly longer PFS than the 2L-non-ICIs group (median PFS: 4.14 . 2.84 months; p < 0.001), and this benefit persisted after PSM (median PFS: 4.21 . 2.87 months; p < 0.001). The 2L-ICIs group also had a significantly higher ORR (ORR: 29.5% . 10.1%; p < 0.001) and DCR (DCR: 67.0% . 51.7%; p < 0.001). Treatment-related adverse events were comparable between the groups, with only one grade 3 rash reported in the 2L-ICIs group. Multivariate Cox regression identified liver metastases, the number of metastatic lesions, and the 1L-PFS as independent predictive factors for PFS. In this study, 2L-ICIs demonstrate significant clinical benefits with acceptable toxicity in ES-SCLC patients who progressed after 1L therapy, supporting their use as a clinically actionable option.

Salicylic acid (SA) acts antagonistically to jasmonic acid (JA) in plant immunity. We previously reported that CATALASE2 (CAT2) promotes JA‐biosynthetic acyl‐CoA oxidase (ACX) activity to enhance plant resistance to necrotrophic Botrytis cinerea, and SA represses JA biosynthesis through inhibiting CAT2 activity, while the underlying mechanism remains to be further elucidated. Here, we report that the truncated CAT2 N‐terminus (CAT2‐N) interacts with and promotes ACX2/3, and CAT2‐N‐overexpressing plants have increased JA accumulation and enhanced resistance to B. cinerea B05.10, but compromised antagonism of SA on JA. Catalase inhibitor treatment or mutating CAT2 active amino acids abolished CAT2 H2O2‐decomposing activity but did not affect its promotion of ACX2/3 activity via interaction. CAT2‐N, a truncated protein with no catalase activity, interacted with and promoted ACX2/3. Overexpressing CAT2‐N in Arabidopsis plants resulted in increased ACX activity, higher JA accumulation, and stronger resistance to B. cinerea B05.10 infection. Additionally, SA dramatically repressed JA biosynthesis and resistance to B. cinerea in the wild type but not in the CAT2‐N‐overexpressing plants. Together, our study reveals that CAT2‐N can be utilized as an accelerator for JA biosynthesis during plant resistance to B. cinerea B05.10, and this truncated protein partly relieves SA repression of JA biosynthesis in plant defence responses. N‐terminal fragment of CATALASE2 interacts with and promotes acyl‐CoA oxidases implicated in JA biosynthesis and enhances plant resistance to Botrytis cinerea, thus CATALASE2‐N could be a genetic tool conferring plant resistance.

[This corrects the article DOI: 10.3389/fimmu.2025.1658017.].

Background: TomoDirect (TD) and intensity-modulated radiotherapy (IMRT) are advanced techniques used in hypofractionated radiotherapy with simultaneous integrated boost (HFRT-SIB) for patients undergoing breast-conserving surgery. This study evaluates the dosimetric impacts of TD and IMRT on the target volume areas and organs at risk (OARs). Methods: This study is a retrospective dosimetric comparison. Thirty patients were enrolled. Computed tomography (CT) images were acquired with a slice thickness of 5 mm. The CT data were subsequently exported to the Pinnacle treatment planning system. IMRT plans were developed using Pinnacle. The TomoHDTM planning station was used for TD planning. For each patient, three treatment plans were generated: TD (field width [FW] = 2.5 cm), TD (FW = 5 cm), and IMRT. The HFRT-SIB prescription was administered as follows: a cumulative dose of 43.5 Gy was delivered to the planning target volume (PTV); a cumulative dose of 49.5 Gy was delivered to the planning gross target volume (PGTV). Results: For both the PGTV and PTV, the homogeneity index (HI) values were lowest with TD (FW = 2.5 cm). The conformity index (CI) values were highest with IMRT for both the PGTV and PTV. Mean target volume coverage met the requirements for the PGTV and PTV across TD with a FW of 2.5 cm, TD with a FW of 5 cm, and IMRT. For the left lung and heart, V5, V10, V20, V30, and the mean dose (Dmean) were the lowest with TD (FW = 2.5 cm). The maximum dose (Dmax) and Dmean for the left anterior descending coronary artery (LAD) were also lowest with TD (FW = 2.5 cm). TD (FW = 5 cm) provided slightly less protection for OARs than TD (FW = 2.5 cm). The average treatment time was 5 minutes for TD (FW = 5 cm) and 9 minutes for TD (FW = 2.5 cm). Conclusions: Compared with IMRT, TD provides better protection of cardiopulmonary function while maintaining target area quality. Overall, when employing TD for HFRT-SIB, a FW of 5 cm is recommended.

Background To determine the efficacy of adjuvant radiotherapy for stage II–III biliary tract carcinoma. Methods We retrospectively analyzed the data of 37 patients who underwent radical resection of biliary tract carcinomas at the Affiliated Hospital of Inner Mongolia Medical University between 2016 and 2020. We analyzed survival differences between patients who did ( n  = 17) and did not ( n  = 20) receive postoperative adjuvant radiotherapy by using Kaplan–Meier analysis. The log-rank test and Cox univariate analysis were used. The Cox proportional risk regression model was used for the multifactorial analysis of factors influencing prognosis. Results The median survival time (28.9 vs. 14.5 months) and the 1-year (82.40% vs. 55.0%) and 2-year survival rates (58.8% vs. 25.0%) were significantly higher among patients who received adjuvant radiotherapy than among those who did not ( χ 2  = 6.381, p  = 0.012). Multifactorial analysis showed that pathological tumor type ( p  = 0.004), disease stage ( p  = 0.021), and adjuvant radiotherapy ( p  = 0.001) were independent prognostic factors in biliary tract carcinoma. Subgroup analyses showed that compared to no radiotherapy, adjuvant radiotherapy significantly improved median survival time in patients with stage III disease (21.6 vs. 12.7 months; p  = 0.017), positive margins (28.9 vs. 10.5 months; p  = 0.012), and T3 or T4 tumors (26.8 vs. 16.8 months; p  = 0.037). Conclusion Adjuvant radiotherapy significantly improved the survival of patients with biliary tract carcinoma, and is recommended especially for patients with stage III disease, positive surgical margins, or ≥ T3. Highlights 1. Adjuvant radiotherapy was an independent prognostic factor for stage II–III BTC. 2. Adjuvant radiotherapy improved the survival of patients with stage III BTC.

Myeloid sarcoma (MS) is a rare extramedullary tumor formed by the abnormal proliferation of immature myeloid cells. It can occur concurrently with or secondary to various myeloid neoplasms, most commonly acute myeloid leukemia (AML). Cervical involvement is extremely rare, and its clinical presentation often mimics that of primary gynecologic malignancies, typically manifesting as vaginal bleeding, a palpable cervical mass, or cervical enlargement. We report the case of a 67-year-old woman with a history of AML who had received multiple lines of chemotherapy and presented with irregular vaginal bleeding since more than 1 month. Cervical biopsy showed diffuse infiltration of atypical myeloid cells, and immunohistochemistry supported the diagnosis of MS. She received pelvic radiotherapy with 6 MV X-ray intensity-modulated radiation therapy combined with intracavitary brachytherapy, and follow-up evaluation 3 months later demonstrated marked shrinkage of the cervical mass. This case highlights that cervical MS is prone to being misdiagnosed and that histopathology with immunohistochemistry is essential for a definitive diagnosis. Even in patients who have undergone multiple lines of systemic therapy and are unable to receive hematopoietic stem cell transplantation, local radiotherapy can achieve rapid and effective local control, and may confer a survival benefit.

Background Opening wedge high tibial osteotomy (OWHTO) is an effective surgical treatment for knee osteoarthritis. This study aimed to explore the feasibility and accuracy of a novel 3D-printed patient-specific instrument (PSI) based on “ H -point” for medial OWHTO in a prospective cadaver study. Methods Twenty-six fresh-frozen lower limbs were collected and randomly divided into two groups: PSI group treated with 3D virtual preoperative planning and a novel 3D-printed PSI; control group with the standard technique. 3D models were reversely reconstructed for preoperative surgical planning, guide plate design, and simulated osteotomy. Anatomic features of “ H -point,” surgical time, fluoroscopic dose, correction accuracy including tibiofemoral angle (FTA) and posterior tibial slope (TS) angle were measured. Results First, H -point was always described as a bony bulge in the posteromedial to the proximal tibia and had a relatively constant relationship with the osteotomy site. Second, the absolute correction error of mFTA and TS were significantly smaller in the PSI group. The effective rate of TS in the PSI group was more concentrated with absolute correction error within 1° and within 2° for 53.3% and 93.3%, compared to 9.1% and 45.5% in the control group. The total operation time, positioning osteotomy time, distraction correction time and fluoroscopy dose in the PSI group were significantly less than those in the control group. Conclusions The novel 3D-printed PSI based on H -point is feasibility and accuracy with advantages in terms of TS, surgery time and radiation dose for OWHTO.

Purpose Achieving a pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (NCRT) remains a challenge for most patients with rectal cancer. Exploring the potential of combining NCRT with immunotherapy or targeted therapy for those achieving a partial response (PR) offers a promising avenue to enhance treatment efficacy. This study investigated the impact of NCRT on the tumor microenvironment in locally advanced rectal cancer (LARC) patients who exhibited a PR. Methods This was a retrospective, observational study. Five patients demonstrating a PR after neoadjuvant treatment for LARC were enrolled in the study. Biopsy samples before treatment and resected specimens after treatment were stained with a panel of 26 antibodies targeting various immune and tumor-related markers, each labeled with distinct metal tags. The labeled samples were then analyzed using the Hyperion imaging system. Results Heterogeneity within the tumor microenvironment was observed both before and after NCRT. Notably, tumor-associated macrophages, CD4 + T cells, CD8 + T cells, CD56 + natural killer cells, tumor-associated neutrophils, cytokeratin, and E-cadherin exhibited slight increase in abundance within the tumor microenvironment following treatment (change ratios = 0.78, 0.2, 0.27, 0.32, 0.17, 0.46, 0.32, respectively). Conversely, the number of CD14 + monocytes, CD19 + B cells, CD45 + CD4 + T cells, collagen I, α-smooth muscle actin, vimentin, and β-catenin proteins displayed significant decreases post-treatment (change ratios = 1.73, 1.92, 1.52, 1.25, 1.52, 1.12, 2.66, respectively). Meanwhile, Foxp3 + regulatory cells demonstrated no significant change (change ratio = 0.001). Conclusions NCRT has diverse effects on various components of the tumor microenvironment in LARC patients who achieve a PR after treatment. Leveraging combination therapies may optimize treatment outcomes in this patient population.

The interaction between ribavirin (RIB) with bovine serum albumin (BSA) has been investigated by fluorescence quenching technique in combination with UV–vis absorption and circular dichroism (CD) spectroscopies under the simulative physiological conditions. The quenching of BSA fluorescence by RIB was found to be a result of the formation of RIB–BSA complex. The binding constants and the number of binding sites were calculated at three different temperatures. The values of thermodynamic parameters ∆ H , ∆ S , ∆ G at different temperatures indicate that hydrophobic and hydrogen bonds played important roles for RIB–BSA association. The binding distance r was obtained according to the theory of FÖrster’s non–radiation energy transfer. The displacement experiments was performed for identifying the location of the binding site of RIB on BSA. The effects of common ions on the binding constant of RIB and BSA were also examined. Finally, the conformational changes of BSA in the presence of RIB were also analyzed by CD spectra and Synchronous fluorescence spectra.