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Piezoelectric vibration sensors (PVSs) are widely applied to vibration detection in aerospace engines due to their small size, high sensitivity, and high-temperature resistance. The precise prediction of their remaining useful life (RUL) under high temperatures is crucial for their maintenance. Notably, digital twins (DTs) provide enormous data from both physical structures and virtual models, which have potential in RUL predictions. Therefore, this work establishes a DT framework containing six modules for sensitivity degradation detection and assessment on the foundation of a five-dimensional DT model. In line with the sensitivity degradation mechanism at high temperatures, a DT-based RUL prediction was performed. Specifically, the PVS sensitivity degradation was described by the Wiener–Arrhenius accelerated degradation model based on the acceleration factor constant principle. Next, an error correction method for the degradation model was proposed using real-time data. Moreover, parameter updates were conducted using a Bayesian method, based on which the RUL was predicted using the first hitting time. Extensive experiments on distinguishing PVS samples demonstrate that our model achieves satisfying performance, which significantly reduces the prediction error to 8 h. A case study was also conducted to provide high RUL prediction accuracy, which further validates the effectiveness of our model in practical use.

The efficacy and safety of donor-derived anti-CD19 CAR T cells vs DLI for the management of relapsed B-cell acute lymphoblastic leukemia (B-ALL) after allo-hematopoietic stem cell transplantation (HSCT) remain unclear. Thirteen B-ALL patients with relapsed after allo-HSCT and thus were treated with donor-derived anti-CD19 CAR T-cell (study group). Fifteen B-ALL patients relapsed after allo-HSCT and thus were treated with DLI (DLI group). The rates of MRD-negative complete remission (61.5%) in the study group were significantly higher than those in the DLI group (13.3%) (p = 0.02). The complete remission duration in study group and DLI group were median 8.0 months (range, 3–25 months) and 4.4 months (range, 1–25 months; p = 0.026), respectively. The overall survival of patients in the study group was superior to that of the DLI group: 9.5 months (range,3–25 months) versus 5.5 months (range, 1–25 months; p = 0.030). One patient with grade 1 acute graft-versus-host disease (aGVHD) was identified in the study group. While five (33.3%) patients in the DLI group developed grades III–IV aGVHD. Three patients (23.07%) developed grade 3 or 4 cytokine release syndrome in the study group. This study suggested that donor-derived anti-CD19 CAR T-cell therapy is promising, safe, and potentially effective for relapsed B-ALL after allo-HSCT and may be superior to DLI.

Soil salinity is a major issue limiting efficient crop production. Seed priming with nanomaterials (nanopriming) is a cost‐effective technology to improve seed germination under salinity; however, the underlying mechanisms still need to be explored. Here, polyacrylic acid coated nanoceria (cerium oxide nanoparticles) (PNC, 9.2 nm, −38.7 mV) are synthesized and characterized. The results show that under salinity, PNC priming significantly increases rapeseed shoot length (41.5%), root length (93%), and seedling dry weight (78%) compared to the no‐nanoparticle (NNP) priming group. Confocal imaging results show that compared with NNP group, PNC priming significantly reduces reactive oxygen species (ROS) level in leaf (94.3% of H2O2, 56.4% of •O2−) and root (38.4% of H2O2, 41.3% of •O2−) of salt stressed rapeseed seedlings. Further, the results show that compared with the NNP group, PNC priming not only increases salicylic acid (SA) content in shoot (51.3%) and root (78.4%), but also upregulates the expression of SA biosynthesis related genes in salt stressed rapeseed. Overall, PNC nanopriming improved rapeseed salt tolerance is associated with both the increase of ROS scavenging ability and the increase of salicylic acid. The results add more information to understand the complexity of mechanisms behind nanoceria priming improved plant salt tolerance. Seed nanopriming to improve plant stress tolerance is an approach with good potential in agricultural application. Herein, it is shown that besides the commonly employed mechanisms i.e., reactive oxygen species (ROS) scavenging, seed priming with CeO2 nanoparticles can also modulate phytohormone levels, such as absicic acid, gibberellic acid 3, and especially the salicylic acid content, to induce salt tolerance in rapeseed.

Antineutrophil cytoplasmic antibody-associated glomerulonephritis (ANCA-GN), a life-threatening vasculitis manifestation, involves systemic endothelial injury and rapid renal decline. Despite limited therapies, the role of ferroptosis, a newly characterized form of regulated cell death, in ANCA-GN remains unexplored. Here, elevated neutrophil extracellular traps (NETs) were identified in ANCA-GN patients and experimental vasculitis models, correlating with endothelial injury markers. Mechanistically, NETs triggered ferroptosis in glomerular endothelial cells (GEnCs) by suppressing manganese superoxide dismutase (MnSOD) activity, exacerbating oxidative stress. To address this, manganese-loaded glucose-based carbon nanoparticles (GCNPs/Mn) were synthesized, demonstrating biocompatibility and antioxidant properties. In vitro, GCNPs/Mn restored MnSOD activity, mitigated mitochondrial dysfunction, and suppressed NF-κB signaling, reversing NET-induced ferroptosis. In ANCA-GN rat models, GCNPs/Mn administration reduced renal injury, lipid peroxidation, and ferroptosis-related protein dysregulation. Mechanistic studies revealed lysosomal Mn release from GCNPs/Mn enhanced MnSOD activity, linking its therapeutic efficacy to antioxidant defense. This study identifies ferroptosis as a novel driver of GEnC injury in ANCA-GN and pioneers GCNPs/Mn as a MnSOD-targeted nanotherapy, bridging critical gaps in understanding and treating this rare disease. Graphical abstract

Cisplatin‐associated acute kidney injury (AKI) is a severe clinical syndrome that significantly restricts the chemotherapeutic application of cisplatin in cancer patients. Ferroptosis, a newly characterized programmed cell death driven by the lethal accumulation of lipid peroxidation, is widely reported to be involved in the pathogenesis of cisplatin‐associated AKI. Targeted inhibition of ferroptosis holds great promise for developing novel therapeutics to alleviate AKI. Unfortunately, current ferroptosis inhibitors possess low bioavailability or perform non‐specific accumulation in the body, making them inefficient in alleviating cisplatin‐associated AKI or inadvertently reducing the anti‐tumor efficacy of cisplatin, thus not suitable for clinical application. In this study, a novel selenium nanomaterial, polyacrylic acid‐coated selenium‐doped carbon dots (SeCD), is rationally developed. SeCD exhibits high biocompatibility and specifically accumulates in the kidney. Administration of SeCD effectively scavenges broad‐spectrum reactive oxygen species and significantly facilitates GPX4 expression by releasing selenium, resulting in strong mitigation of ferroptosis in renal tubular epithelial cells and substantial alleviation of cisplatin‐associated AKI, without compromising the chemotherapeutic efficacy of cisplatin. This study highlights a novel and promising therapeutic approach for the clinical prevention of AKI in cancer patients undergoing cisplatin chemotherapy. Intravenously injected SeCD mainly accumulates in the kidney, where SeCD directly scavenges ROS and preserves mitochondrial integrity during the cisplatin challenge. Furthermore, SeCD releases selenium to facilitate GPX4 expression when encountering ROS under cisplatin exposure. Through these mechanisms, SeCD counteracts ferroptosis and alleviates cisplatin‐associated AKI, without compromising the anti‐tumor efficacy of cisplatin.

Background Microbes have been shown to play a crucial role in various ecosystems. Many human diseases have been proved to be associated with bacteria, so it is essential to extract the interaction between bacteria for medical research and application. At the same time, many bacterial interactions with certain experimental evidences have been reported in biomedical literature. Integrating this knowledge into a database or knowledge graph could accelerate the progress of biomedical research. A crucial and necessary step in interaction extraction (IE) is named entity recognition (NER). However, due to the specificity of bacterial naming, there are still challenges in bacterial named entity recognition. Results In this paper, we propose a novel method for bacterial named entity recognition, which integrates domain features into a deep learning framework combining bidirectional long short-term memory network and convolutional neural network. When domain features are not added, F1-measure of the model achieves 89.14%. After part-of-speech (POS) features and dictionary features are added, F1-measure of the model achieves 89.7%. Hence, our model achieves an advanced performance in bacterial NER with the domain features. Conclusions We propose an efficient method for bacterial named entity recognition which combines domain features and deep learning models. Compared with the previous methods, the effect of our model has been improved. At the same time, the process of complex manual extraction and feature design are significantly reduced.

Soil salinity is a big environmental issue affecting crop production. Although seed nanopriming has been widely used to improve seed germination and seedling growth under salinity, our knowledge about the underlying mechanisms is still insufficient. Herein, we newly synthesized selenium-doped carbon dots nanoparticles coated with poly acrylic acid (poly acrylic acid coated selenium doped carbon dots, PAA@Se-CDs) and used it to prime seeds of rapeseeds. The TEM (transmission electron microscope) size and zeta potential of PAA@Se-CDs are 3.8 ± 0.2 nm and −30 mV, respectively. After 8 h priming, the PAA@Se-CDs nanoparticles were detected in the seed compartments (seed coat, cotyledon, and radicle), while no such signals were detected in the NNP (no nanoparticle control) group (SeO2 was used as the NNP). Nanopriming with PAA@Se-CDs nanoparticles increased rapeseeds germination (20%) and seedling fresh weight (161%) under saline conditions compared to NNP control. PAA@Se-CDs nanopriming significantly enhanced endo-β-mannanase activities (255% increase, 21.55 µmol h−1 g−1 vs. 6.06 µmol h−1 g−1, at DAS 1 (DAS, days after sowing)), total soluble sugar (33.63 mg g−1 FW (fresh weight) vs. 20.23 mg g−1 FW) and protein contents (1.96 µg g−1 FW vs. 1.0 µg g−1 FW) to support the growth of germinating seedlings of rapeseeds under salt stress, in comparison with NNP control. The respiration rate and ATP content were increased by 76% and 607%, respectively. The oxidative damage of salinity due to the over-accumulation of reactive oxygen species (ROS) was alleviated by PAA@Se-CDs nanopriming by increasing the antioxidant enzyme activities (SOD (superoxide dismutase), POD (peroxidase), and CAT (catalase)). Another mechanism behind PAA@Se-CDs nanopriming improving rapeseeds salt tolerance at seedling stage was reducing sodium (Na+) accumulation and improving potassium (K+) retention, hence increasing the K+/Na+ ratio under saline conditions. Overall, our results not only showed that seed nanopriming with PAA@Se-CDs could be a good approach to improve salt tolerance, but also add more knowledge to the mechanism behind nanopriming-improved plant salt tolerance at germination and early seedling growth stage.

Background Selinexor 80 mg combined with low-dose dexamethasone (Sd) demonstrated significant clinical benefit in patients with relapsed/refractory multiple myeloma (RRMM) who had disease refractory to a proteasome inhibitor (PI), an immunomodulator (IMiD), and an anti-CD38 monoclonal antibody based on a global phase II STORM study. The present study, MARCH, addresses China regulatory needs to further validate the data from STORM in Chinese patients with RRMM. Methods The MARCH study was conducted at 17 sites in China, where eligible Chinese RRMM patients who had disease refractory to PI and IMiD were enrolled. Selinexor 80 mg combined with dexamethasone 20 mg was administered orally on day 1 and day 3 of each week in 4-week cycles. The primary endpoint was the overall response rate (ORR) per an independent review committee, with the null hypothesis of ≤15%. Patients who received at least 1 dose of study treatment were included in the safety population. The pharmacokinetic (PK) profile was characterized by parameter and ethnicity sensitivity analyses. Results A total of 82 patients with RRMM were enrolled in the study, with a median age of 60 years. Of the 82 patients, 55 patients (67.1%) had high-risk cytogenetic abnormalities, defined as one or more of del 17p13, t(4;14), t(14;16), or 1q amplification identified by fluorescence in situ hybridization (FISH); 18 patients (22.0%) had abnormal renal function. Enrolled patients were heavily pre-treated with a median prior regimen number of 5. All 82 patients (100%) were refractory to both PI and IMiD, including 20 patients (24.4%) categorized as triple-class refractory population (refractory to PI, IMiD, and daratumumab). Ten patients (12.2%) had undergone CAR-T therapy. ORR was 29.3% (95% CI 19.7, 40.4) with a median DOR of 4.7 months. The median PFS and OS were 3.7 and 13.2 months, respectively. ORR was 25.0% (95% CI 8.7, 49.1) in the triple-class refractory population. Efficacy was consistent across various subgroups. The most frequent grade 3/4 adverse events (AEs) included anemia (57.3%), thrombocytopenia (51.2%), lymphopenia (42.7%), neutropenia (40.2%), hyponatremia (29.3%), and lung infection (26.8%). Serious AEs were reported in 54.9% of patients. No significant drug accumulation was shown following multiple administrations. No human PK ethnicity difference was identified between Chinese and western patients. Conclusions With an encouraging ORR, the MARCH study has demonstrated that selinexor combined with low-dose dexamethasone (Sd) delivers meaningful clinical benefit to Chinese patients with RRMM, including triple-class refractory patients. AEs were expected and manageable with supportive care and dose modification. Trial registration ClinicalTrials.gov, NCT03944057 (May 09, 2019); Chinadrugtrials.org.cn , CTR20190858 (June 05, 2019)

Piezoelectric vibration sensors (PVSs) are widely used in high-temperature environments, such as vibration measurements in aero-engines, because of their high accuracy, small size, and high temperature resistance. Accurate prediction of its RUL (Remaining Useful Life) is essential for applying and maintaining PVSs. Based on PVSs’ characteristics and main failure modes, this work combines the Digital-Twin (DT) and Long Short-Term Memory (LSTM) networks to predict the RUL of PVSs. In this framework, DT can provide rich data collection, analysis, and simulation capabilities, which have advantages in RUL prediction, and LSTM network has good results in predicting time sequence data. The proposed method exploits the advantages of those techniques in feature data collection, sample optimization, and RUL multiclassification. To verify the prediction of this method, a DT platform is established to conduct PVS degradation tests, which generates sample datasets, then the LSTM network is trained and validated. It has been proved that prediction accuracy is more than 99.7%, and training time is within 94 s. Based on this network, the RUL of PVSs is predicted using different test samples. The results show that the method performed well in prediction accuracy, sample data utilization, and compatibility.