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Zero-field nuclear magnetic resonance (NMR) offers magnet-free access to nuclear spin-spin (scalar J ) couplings, which define an intrinsic, molecule-specific frequency scale. However, the transient nature of zero-field NMR signals constrain spectral resolution and frequency stability. Here we introduce quantum J -oscillators that exploit J -couplings in molecules to produce phase-coherent continuous oscillations. Operated in zero magnetic field and driven by digital feedback, they generate sub-hertz to a few tens of hertz frequencies. In a proof-of-principle experiment on [ 15 N]-acetonitrile, the oscillator achieves a 340 μ Hz linewidth over 3600 s, more than two orders of magnitude narrower than in conventional zero-field NMR. This methodology may facilitate precision measurements of J -coupling constants and enables discrimination of molecules whose zero-field NMR spectra are otherwise difficult to resolve. In addition, the combination of strongly coupled spin systems and programmable feedback turns J -oscillators into a compact tabletop platform for exploring nonlinear spin dynamics, including chaos and dynamical phase transitions. By uniting high-resolution spectroscopy and controllable quantum dynamics in a single, magnet-free setup, J -oscillators open new opportunities for applications where ultraprecise frequency references or molecular fingerprints are required. Magnet-free J -oscillators use internal spin-spin couplings in molecules and digital feedback to generate continuous, ultra-stable zero-field NMR signals, reaching up to 100x narrower linewidths for sharper molecular fingerprints.

To evaluate the association between tramadol use and short-term outcomes, including 28-day mortality, intensive care unit (ICU) mortality, and ICU length of stay, in critically ill patients undergoing cardiac surgery. This retrospective cohort study included 3,544 participants from the MIMIC-IV database. A comprehensive analytical approach was employed, including multivariate Cox regression, subgroup analysis, propensity score matching (PSM), inverse probability weighting (IPW), doubly robust estimation, and E-value calculation. Receiver operating characteristic (ROC) curves and the DeLong test were used to compare the predictive performance of different opioids, and SHAP analysis was employed for model interpretation. Tramadol use was consistently associated with a significant reduction in 28-day mortality across all models. The hazard ratios (HR) ranged from 0.305 to 0.341 after rigorous adjustment and matching (all < 0.05). Subgroup analyses demonstrated the robustness of this protective association, and a significant interaction was observed with respect to surgery type after PSM. Furthermore, tramadol demonstrated superior predictive performance for 28-day mortality (AUC = 0.603) compared to other opioids, including fentanyl, hydromorphone, morphine, and oxycodone AUC range: 0.523-0.597). However, no significant association was found with secondary outcomes like ICU mortality or length of stay. Tramadol administration is independently associated with a significantly lower risk of 28-day mortality in cardiac surgery patients, showing better predictive utility than other common opioids, which may inform postoperative analgesic strategies.

Purpose To explore the development and validation of automated machine learning (AutoML) models for 18 F-FDG PET imaging-based radiomics signatures to predict treatment response in elderly patients with diffuse large B-cell lymphoma (DLBCL). Methods A retrospective analysis was conducted on 175 elderly (≥ 60 years) DLBCL patients diagnosed between March 2015 and March 2023 at two medical centers, with a total of 1010 lesions. The baseline PET imaging-based radiomics features of the training cohort were processed using AutoML model AutoGluon to generate a radiomics score (radscore) and predict treatment response at the lesion and patient levels. Furthermore, a multivariable logistic analysis was used to design and evaluate a multivariable model in the training and validation cohorts. Results ROC curve analysis showed that the radscore generated by AutoML exhibited higher accuracy in predicting treatment response at the lesion level compared to metabolic parameters (SUVmax, MTV, and TLG) in both the training group (AUC: 0.791, 0.542, 0.667, 0.651, respectively) and the validation group (AUC: 0.712, 0.616, 0.639, 0.657, respectively). Multivariable logistic analysis indicated that NCCN-IPI (OR = 5.427, 95% CI: 1.163–25.317), BCL-2 (OR = 3.714, 95% CI: 1.406–9.816), TMTV (OR = 4.324, 95% CI: 1.095–17.067), and avg-radscore (OR = 3.176, 95% CI: 1.313-7. 686) were independent predictors of treatment response. The multivariable model comprising NCCN-IPI, BCL-2, TMTV, and avg-radscore outperformed conventional models and clinical-pathological models in predicting treatment response. ( P <0.05). Conclusion The radscore generated by AutoML can predict the treatment response of elderly DLBCL patients, potentially aiding in clinical decision-making.

Objectives To investigate the prognostic value of PET radiomics feature in the prognosis of patients with primary gastrointestinal diffuse large B cell lymphoma (PGI-DLBCL) treated with R-CHOP-like regimen. Methods A total of 140 PGI-DLBCL patients who underwent pre-therapy [ 18 F] FDG PET/CT were enrolled in this retrospective analysis. PET radiomics features obtained from patients in the training cohort were subjected to three machine learning methods and Pearson’s correlation test for feature selection. Support vector machine (SVM) was used to build a radiomics signature classifier associated with progression-free survival (PFS) and overall survival (OS). A multivariate Cox proportional hazards regression model was established to predict survival outcomes. Results A total of 1421 PET radiomics features were extracted and reduced to 5 features to build a radiomics signature which was significantly associated with PFS and OS ( p < 0.05). The combined model incorporating radiomics signatures, metabolic metrics, and clinical risk factors showed high C-indices in both the training (PFS: 0.825, OS: 0.834) and validation sets (PFS: 0.831, OS: 0.877). Decision curve analysis (DCA) demonstrated that the combined models achieved the most net benefit across a wider reasonable range of threshold probabilities for predicting PFS and OS. Conclusion The newly developed radiomics signatures obtained by the ensemble strategy were independent predictors of PFS and OS for PGI-DLBCL patients. Moreover, the combined model with clinical and metabolic factors was able to predict patient prognosis and may enable personalized treatment decision-making. Key Points • Radiomics signatures generated from the optimal radiomics feature set from the [ 18 F ] FDG PET images can predict the survival of PGI-DLBCL patients. • The optimal radiomics feature set is constructed by integrating the feature selection outputs of LASSO, RF, Xgboost, and PC methods. • Combined models incorporating radiomics signatures from 18 F-FDG PET images, metabolic parameters, and clinical factors outperformed clinical models, and NCCN-IPI.

This study investigated the impact of rhizosphere fungi on the quality of Atractylodes macrocephala in China by analyzing the physical and chemical properties, enzyme activities, and community structures of soil samples from four distinct regions: Pan’an (PA), Bozhou (BZ), Zhoukou (ZK), and Anguo (AG). The results indicated that both biomass and active components of A. macrocephala were significantly higher in authentic production areas compared to emerging ones. The rhizosphere soil network in PA, identified as an authentic production area, exhibited the most complex structure, with pH levels significantly negatively correlated with 12 major fungal genera. Notably, fungi such as Rozellomycota , Mortierella , and Basidiomycota were linked to the quality of A. macrocephala through their roles in organic matter decomposition. Additionally, Saitozyma was found to be a central component of the rhizosphere fungal community, with a relative abundance of 2.19%, markedly higher than in emerging production areas (< 0.1%). These findings provide critical insights into the factors affecting A. macrocephala quality across different regions, offering valuable guidance for the sustainable cultivation of this essential medicinal plant in China.

Primary central nervous system lymphoma (PCNSL) is a rare subtype of extranodal non-Hodgkin lymphoma, and the most frequent histological type is diffuse large B-cell lymphoma (DLBCL). Bruton's tyrosine kinase inhibitor (BTKi) has shown clinical activity in DLBCL. We herein report a 53-year-old man who presented with binocular diplopia, gait instability, dizziness and bucking. He was diagnosed with PCNSL by cranial magnetic resonance imaging (MRI) scan and brain biopsy. Next-generation sequencing (NGS) examination identified multiple genetic abnormalities. The patient was started on a high-dose methotrexate (HD-MTX)-based protocol for two courses. However, the patient developed disease progression. The patient's phenotypic and genetic characteristics strongly suggested BN2-DLBCL, and zanubrutinib was added to the subsequent chemotherapy regimen. The treatment was well tolerated, and complete remission (CR) was achieved after three courses of chemotherapy with the new regimen. The patient then received autologous hematopoietic stem cell transplantation after four courses of chemotherapy with the new regimen. MRI revealed stable CR. Here, we report a successful case of refractory PCNSL treated with zanubrutinib. Small molecules, such as zanubrutinib, may be selectively integrated into first-line regimens of PCNSL to enhance curative effect and reduce recurrence. Keywords: primary central nervous system lymphoma, Bruton's tyrosine kinase, zanubrutinib, targeted therapy

Extracellular vesicles (EVs) are vesicle-like structures composed of lipid bilayers, which can be divided into apoptotic bodies, microbubbles and exosomes. They are nanoparticles used for the exchange of information between cells. EVs contains many substances, including protein. With the development of proteomics, we know more about the types and functions of protein in vesicles. The potential functions of proteins in the envelope are mainly discussed, including cell wall construction, fungal virulence transmission, signal transmission and redox reactions, which provides a new perspective for studying the interaction mechanism between fungi and other organisms. The fungal protein markers of EVs are also summarized, which provided an exploration tool for studying the mechanism of vesicles. In addition, the possible role of immune protein in the EVs in the treatment of human diseases is also discussed, which provides new ideas for vaccine development.

Adult muscle satellite cells (MuSCs) are mostly quiescent in uninjured muscles under normal homeostasis. Although several mechanisms underlying quiescence maintenance are known, our understanding of the process remains incomplete. Here, we show that Keap1 regulates MuSC quiescence maintenance by promoting Nrf2 protein degradation. Inducible deletion of Keap1 activates MuSCs to different extent in a sex-specific manner via differential Nrf2 protein levels: in Keap1 -null MuSCs from male mice, Nrf2 protein is at an intermediate level due to the action of a GSK3β-dependent Nrf2 degradation system, which promotes mutant MuSCs to enter a G Alert -like state; in Keap1 -null MuSCs from female mice, the loss of Keap1 together with estrogen-mediated GSK3β inactivation renders Nrf2 at its highest level, which induces the expression of multiple metabolic genes resulting in metabolic reprogramming, spontaneous activation and gradual depletion of MuSCs. Consistently, interference of selected Nrf2-regulated metabolic genes impairs early activation of MuSCs. Thus, Keap1/Nrf2 regulates quiescence maintenance and early activation of MuSCs independently of its canonical roles in the antioxidant response. Using mouse models, the authors show that loss of Keap1 in adult muscle stem cells (MuSCs) impairs quiescence maintenance in a sex-specific manner and reveal non-canonical roles of Keap1/Nrf2 in quiescence maintenance and early activation of MuSCs.

Central to homologous recombination (HR) is the assembly of Rad51 recombinase on single-strand DNA (ssDNA), forming the Rad51-ssDNA filament. How the Rad51 filament is efficiently established and sustained remains partially understood. Here, we find that the yeast ubiquitin ligase Bre1 and its human homolog RNF20, a tumor suppressor, function as recombination mediators, promoting Rad51 filament formation and subsequent reactions via multiple mechanisms independent of their ligase activities. We show that Bre1/RNF20 interacts with Rad51, directs Rad51 to ssDNA, and facilitates Rad51-ssDNA filament assembly and strand exchange in vitro. In parallel, Bre1/RNF20 interacts with the Srs2 or FBH1 helicase to counteract their disrupting effect on the Rad51 filament. We demonstrate that the above functions of Bre1/RNF20 contribute to HR repair in cells in a manner additive to the mediator protein Rad52 in yeast or BRCA2 in human. Thus, Bre1/RNF20 provides an additional layer of mechanism to directly control Rad51 filament dynamics. Here the authors report that the yeast ubiquitin E3 ligase Bre1 and its human homolog RNF20 function as recombination mediator proteins by promoting Rad51-ssDNA assembly, Rad51 replacement of ssDNA-bound RPA while antagonizing the activities of Srs2 or FBH1 anti-recombinase.

It is widely accepted that lysosomes are essential for cell homeostasis, and autophagy plays an important role in tumor development. Here, we found FV-429, a synthetic flavonoid compound, inhibited autophagy flux, promoted autophagosomes accumulation, and inhibited lysosomal degradation in T-cell malignancies. These effects were likely to be achieved by lysosomal dysregulation. The destructive effects of FV-429 on lysosomes resulted in blockage of lysosome-associated membrane fusion, lysosomal membrane permeabilization (LMP), and cathepsin-mediated caspase-independent cell death (CICD). Moreover, we initially investigated the effects of autophagy inhibition by FV-429 on the therapeutic efficacy of chemotherapy and found that FV-429 sensitized cancer cells to chemotherapy agents. Our findings suggest that FV-429 could be a potential novel autophagy inhibitor with notable antitumor efficacy as a single agent.