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Genome instability is a hallmark of cancer cells and can be accelerated by defects in cellular responses to DNA damage. This feature of malignant cells opens new avenues for tumor targeted therapy. MRE11-RAD50-NBS1 complex plays a crucial role in sensing and repair of DNA damage. Through interacting with other important players of DNA damage response, MRE11-RAD50-NBS1 complex is engaged in various DNA damage repair pathways. Mutations in any member of this complex may lead to hypersensitivity to genotoxic agents and predisposition to malignancy. It is assumed that the defects in the complex may contribute to tumorigenesis and that treatments targeting the defect may be beneficial to cancer patients. Here, we summarized the recent research findings of the role of MRE11-RAD50-NBS1 complex in tumorigenesis, cancer treatment and discussed the potential approaches of targeting this complex to treat cancer.

Plants release large amounts of volatile organic compounds (VOCs) in response to attackers. Several VOCs can serve as volatile signals to elicit defense responses in undamaged tissues and neighboring plants, but many questions about the ecological functions of VOCs remain unanswered. Tea plants are impacted by two harmful invaders, the piercing herbivore Empoasca ( Matsumurasca ) onukii Matsuda and the pathogen Colletotrichum fructicola . To determine the VOC signals in tea, we confirmed CsOPR3 as a marker gene and set up a rapid screening method based on a 1.51 kb CsOPR3 promoter fused with a β-glucuronidase (GUS) reporter construct ( OPR3p::GUS ) in Arabidopsis . Using this screening system, a terpenoid volatile ( E )-nerolidol was identified as a potent signal that elicits plant defenses. The early responses triggered by ( E )-nerolidol included the activation of a mitogen-activated protein kinase and WRKY, an H 2 O 2 burst, and the induction of jasmonic acid and abscisic acid signaling. The induced plants accumulated high levels of defense-related chemicals, which possessed broad-spectrum anti-herbivore or anti-pathogen properties, and ultimately triggered resistance against Empoasca onukii and Colletotrichum fructicola in tea. We propose that these findings can supply an environmentally friendly management strategy for controlling an insect pest and a disease of tea plants.

The tea plant ( Camellia sinensis ) suffers heavily from a harmful piercing pest, the tea green leafhopper (TLH) Empoasca ( Matsumurasca ) onukii Matsuda. In the present study, we studied the effect of an efficient elicitor of plant disease resistance, the β-1,3-glucan laminarin, on the induced defense against TLH in tea plants. Defense responses elicited by laminarin in tea include the activation of mitogen-activated protein kinases and WRKY, the burst of H 2 O 2 , salicylic acid, and abscisic acid, and the accumulation of direct-defense chemicals (including chitinase, phenylalanine ammonia lyase, callose, polyphenol oxidase, and flavonol synthase), as well as the production of volatile compounds. The laminarin-treated tea plants reduced the performance of TLH and enhanced the attractiveness to the egg parasitoid wasp of TLH, Stethynium empoascae Subba Rao. In the field experiment, laminarin application effectively reduced the number of TLH by attracting parasitoids. These results suggest that laminarin can induce protection against TLH by regulating signaling pathways in tea plant. Our study also proposes an environment friendly strategy for the integrated management of an economically important piercing pest.

Whether the anesthesia technique, inhalational general anesthesia (IGA) or propofol-based anesthesia (PBA), influences the long-term survival of non-metastatic breast cancer (eBC) remain unclear and controversial. We carried out a literature search on 16thJuly, 2022 for studies comparing IGA and PBA in eBC undergoing standard surgery, according to PRISMA 2020. The major endpoint in our study was overall survival (OS). Seventeen studies including four randomized clinical trials and thirteen retrospective cohort studies were included in the meta-analysis. Ten studies provided data for crude OS in unweighted eBC patients (imbalance in baseline characteristics). The summarized estimate HRs of the PBA group versus the IGA group (ten studies, N = 127,774, IGA group: 92,592, PBA group: 35,182.) was 0.83 (95%CI: 0.78–0.89). Compared with IGA, PBA was associated with both better 1-year OS (two studies, N = 104,083, IGA group: 84,074, PBA group: 20,009. Pooled HR = 0.80, 0.73–0.89) and 5-year OS (six studies, N = 121,580, IGA group: 89,472, PBA group: 32,108. HR = 0.80, 0.74–0.87). Ten studies applied PSM method to balance the baseline characteristics. In these weighted patients, PBA still showed a better OS (ten studies, N = 105,459, IGA group: 79,095, PBA group: 26,364. HR = 0.93, 0.87–1.00), a better 1-year OS (two studies, N = 83,007, IGA group: 67,609, PBA group: 15,398. HR = 0.88, 0.78–0.98) and a trend towards a better 5-year OS (nine studies, N = 121,580, IGA group: 76,797, PBA group: 24,066. HR = 0.95, 0.88–1.03). Loco-regional recurrence-free survival (LRRFS) was also better in PBA group (HR = 0.73, 0.61–0.86). The present study is the first comprehensive meta-analysis to demonstrate that propofol-based anesthesia could significantly improve OS and LRRFS in non-metastatic breast cancer patients, compared with inhalational anesthesia.

For plant volatiles to mediate interactions in tritrophic systems, they must convey accurate and reliable information to insects. However, it is unknown whether the ratio of compounds in plant volatile blends remains stable during wind transmission. In this study, volatiles released from an odor source were collected at different points in a wind tunnel and analyzed. The variation in the amounts of volatiles collected at different points formed a rough cone shape. The amounts of volatiles collected tended to decrease with increasing distance from the odor source. Principal component analyses showed that the volatile profiles were dissimilar among different collection points. The profiles of volatiles collected nearest the odor source were the most similar to the released odor. Higher wind speed resulted in a clearer spatial distribution of volatile compounds. Thus, variations in the ratios of compounds in odor plumes exist even during transport over short distances.

There has been a lot of research on flight delays. But it is more useful and difficult to estimate the departure delay time especially three hours before the scheduled time of departure, from which passengers can reasonably plan their travel time and the airline and airport staff can schedule flights more reasonably. In this paper, we develop a Spatio-temporal Graph Dual-Attention Neural Network (SGDAN) to learn the departure delay time for each flight with real-time conditions at three hours before the scheduled time of departure. Specifically, it first models the air traffic network as graph sequences, what is, using a heterogeneous graph to model a flight and its adjacent flights with the same departure or arrival airport in a special time interval, and using a sequence to model the flight and its previous flights that share the same aircraft. The main contributions of this paper are using heterogeneous graph-level attention to learn the influence between the flight and its adjacent flight together with sequence-level attention to learn the influence between the flight and its previous flight in the flight sequence. With aggregating features from the learned influence from both graph-level and sequence-level attention, SGDAN can generate node embedding to estimate the departure delay time. Experiments on a real-world large-scale data set show that SGDAN produces better results than state-of-the-art models in the accurate flight delay time estimation task.

Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have obvious advantages over MSC therapy. But the strong procoagulant properties of MSC-EVs pose a potential risk of thromboembolism, an issue that remains insufficiently explored. In this study, we systematically investigated the procoagulant activity of large EVs derived from human umbilical cord MSCs (UC-EVs) both in vitro and in vivo. UC-EVs were isolated from cell culture supernatants. Mice were injected with UC-EVs (0.125, 0.25, 0.5, 1, 2, 4 μg/g body weight) in 100 μL PBS via the tail vein. Behavior and mortality were monitored for 30 min after injection. We showed that these UC-EVs activated coagulation in a dose- and tissue factor-dependent manner. UC-EVs-induced coagulation in vitro could be inhibited by addition of tissue factor pathway inhibitor. Notably, intravenous administration of high doses of the UC-EVs (1 μg/g body weight or higher) led to rapid mortality due to multiple thrombus formations in lung tissue, platelets, and fibrinogen depletion, and prolonged prothrombin and activated partial thromboplastin times. Importantly, we demonstrated that pulmonary thromboembolism induced by the UC-EVs could be prevented by either reducing the infusion rate or by pre-injection of heparin, a known anticoagulant. In conclusion, this study elucidates the procoagulant characteristics and mechanisms of large UC-EVs, details the associated coagulation risk during intravenous delivery, sets a safe upper limit for intravenous dose, and offers effective strategies to prevent such mortal risks when high doses of large UC-EVs are needed for optimal therapeutic effects, with implications for the development and application of large UC-EV-based as well as other MSC-EV-based therapies.

Background The efficiency of capecitabine has been proven in early-stage triple negative breast cancer (eTNBC) with residue invasive tumor (non-pCR) after standard neoadjuvant chemotherapy (NACT). However, for those unselected eTNBC patients without screening from NACT (i.e., newly diagnosed eTNBC patients undergoing breast surgery followed by adjuvant systemic therapy), the value of capecitabine has still remains unclear. We performed a meta-analysis of randomized controlled trials (RCTs) to evaluate whether additional capecitabine in eTNBC patients could improve clinical outcomes. Methods Seven RCTs (USO 01062, FinXX, GEICAM/2003, CREATE-X, CIBOMA/2004, CBCSG-010 and SYSUCC-001) were identified in online databases until December 2020 and included in the meta-analysis. We extracted the survival data including disease/relapse-free survival (DFS/RFS) and overall survival (OS), and utilized the STATA software to calculate the summarized hazard ratios (HRs) and 95% confidence intervals (95%CIs). Results A total of 3329 eTNBC patients were enrolled in this meta-analysis, with 1640 receiving standard neo−/adjuvant chemo-regimes alone, and the other 1689 receiving an additional capecitabine use, respectively. Both DFS and OS were significantly improved with the addition of capecitabine, and the benefits remained consistent in those unselected eTNBC patients without screening from NACT. Subgroup analysis further proved that this improvement in DFS was significant in both nodal negative and positive patients. Similar benefits are also found across menopausal status (both pre- and post-menopause). Regarding toxicity, the hand-foot syndrome and neutropenia are the most common capecitabine related adverse events, and are mostly tolerable. Conclusions The present meta-analysis of RCTs demonstrates for the first time that adding capecitabine to standard chemo-regimens could improve both DFS and OS in unselected eTNBC patients, and this benefit remains consistent regardless of nodal status and menopausal status, which may lead eTNBC therapy into a new era.

The long-chain effects of eruptive solar activities on Earth’s magnetosphere, ionosphere, and the mid-to-lower atmospheric circulation are an important theoretical research topic in the fields of space weather and atmospheric science. Understanding the impact of space weather on aviation holds substantial economic value. It is well-known that flight times for polar routes may increase during solar proton events (SPEs) due to the necessity of avoiding high-energy particles. However, changes in atmospheric circulation due to SPEs and their impact on flight times have not been reported yet. This study systematically analyzed 15 pairs of representative international air routes, comprising a total of 16,037 flight records affected by the polar jet stream between 2015 and 2019. An unpaired two-sample two-tailed t-test revealed that 86.67% of westbound flights had shorter durations, while 86.67% of eastbound flights had longer durations during SPEs compared to quiet periods, with an average change of approximately 7 min. Further investigation into 42 SPEs during an entire solar cycle (11 years) indicates that the poleward shift of the polar jet stream, associated with high-energy particle precipitation, is the fundamental reason for the asymmetrical changes in flight times. This is the first report detailing the impact of SPEs on atmospheric circulation and flight times. Our findings reveal the long-chain mechanism by which SPEs directly influence the circulation of Earth’s lower atmosphere. These results are also crucial for aviation, as they can help airlines optimize routes, reduce fuel costs, and contribute to climate change mitigation efforts.

To suppress chatter is very important for ensuring processing quality and efficiency in ultrasonic-assisted grinding of thin-walled workpiece of SiCp/Al composites. Based on the chatter mechanism analysis, a stability analysis model is built and the analytical method is proposed. The cutting parameters can be selected reasonably based on the lobe diagram of stability, and the experiments were conducted using the parameters of selected points on lobe diagram. The experimental results show that the cutting force and surface roughness of unstable points are much larger than that of stable points, the vibration marks appear on the workpiece surface with unstable machining, and the surface quality is better in stable machining, which indicate that the chatter could be suppressed by this method to guarantee machining quality and efficiency.