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Asparaginase (ASP) is the cornerstone drug in the treatment of extranodal NK/T-cell lymphoma (ENKTCL), and the mechanisms of resistance to ASP remain largely unknown. Long non-coding RNAs play important roles in chemotherapy resistance in various cancers. However, the expression of BCYRN1 and its role in ENKTCL still remain unidentified. Lentivirus-mediated BCYRN1 overexpression and knockdown were performed in SNK-6 cells. Cell autophagy was analyzed by adenovirus expressing GFP-LC3B fusion protein. RNA pull-down and RNA Binding Protein Immunoprecipitation Assay were performed to investigate the relationship between BCYRN1 and p53. Western blot analysis was performed to assess the effect of BCYRN1 on different autophagy pathways. Finally, in vivo xenograft tumor model was constructed to analyze the effect of BCYRN1 on tumor growth and ASP resistance. BCYRN1 was overexpressed in ENKTCL than normal NK cells, and patients with higher expression had significantly inferior progression-free survival (PFS). The IC50 value of ASP was significantly increased in BCYRN1-overexpressed SNK-6 cells and BCYRN1 overexpression could resist the inhibitory effect of ASP on proliferation. ASP could induce concurrent apoptosis and autophagy in ENKTCL, and the latter process was enhanced by overexpression of BCYRN1, mainly through affecting both PI3K/AKT/mTOR and p53/mTOR pathways. BCYRN1 could induce the degradation of p53 via ubiquitination, thus resulting in enhancement of autophagy and ASP resistance, which could be reversed by drug-induced autophagy inhibition. The effect of BCYRN1 on tumor growth and autophagy were confirmed in vivo xenograft model. It was found that BCYRN1 was a valuable prognostic biomarker in ENKTCL. BCYRN1 could promote resistance to ASP by inducing autophagy, which could be reversed by inhibition of autophagy. Our findings highlight the feasibility of combining autophagy inhibition and ASP in the treatment of ENKTCL.

Background The distal aspect of the second molar (d-M2) often exhibits infrabony defects due to the adjacent third molar. Although the defects can be treated by guided tissue regeneration (GTR) after removing the third molar, the optimal timing remains uncertain following third molar removal in clinical decision-making. This study aimed to compare delayed and immediate GTR treatments to assist in clinical decision-making. Methods D-M2 infrabony defects with a minimum 1-year follow-up were collected and divided into three groups: Immediate GTR group, which underwent third molar extraction and received GTR simultaneously; Delayed GTR group, which underwent delayed GTR at least 3 months after third molar extraction; and Control group, which underwent only scaling and root planing during third molar extraction. The clinical and radiographic parameters related to the infrabony defect before GTR and post-surgery were evaluated using the Kruskal-Wallis test or one-way ANOVA, followed by post-hoc Dunn’s test or the Bonferroni test for pairwise comparisons. Results A total of 109 d-M2 infrabony defects were assessed. No significant differences were found between the two GTR groups, although both of them showed significant reductions in infrabony defect depth: the immediate GTR group (2.77 ± 1.97 mm vs. 0.68 ± 1.03 mm, p  < 0.001) and the delayed GTR group (2.98 ± 1.08 mm vs. 0.68 ± 1.03 mm, p  < 0.001) compared to the control group. Conclusion GTR can effectively improve d-M2 infrabony defects when the third molar is removed, whether simultaneously or delayed. Patients may experience less discomfort with immediate GTR treatment as it requires only one surgery.

Background Primary ocular adnexal extranodal marginal zone mucosa‐associated lymphoid tissue lymphoma (OAML) is a rare subtype of non‐Hodgkin's lymphoma, and no consensus has been defined concerning the optimal treatment strategies. This study aims to investigate the associations of disease characteristics and different treatments with long‐term outcomes of patients with localized OAML. Methods A large retrospective cohort study was conducted in a single‐center of China, and 166 patients with newly diagnosed primary localized OAML were enrolled. Detailed data of disease characteristics at diagnosis and treatments were collected for all patients. We compared treatment response and progression‐free survival (PFS) among patients with different characteristics and treatments. Results Of the 166 patients, 52 received complete resection of neoplasm, whereas 114 had residual lesion after surgery. Among the 114 patients, 61 underwent watchful waiting and 53 received further treatment including localized radiotherapy, chemotherapy, or combined radiotherapy and chemotherapy. Median follow‐up was 49 months. A total of 31 patients had disease progression or relapse, including four patients with such event more than five years after initial treatment. The 5‐year PFS was 73.9%, 70.6%, and 85.9%, whereas the 10‐year PFS was 69.3%, 59.2%, and 79.3%, among patients with complete resection of neoplasm, patients in the watchful waiting group and patients with further treatment, respectively. Patients with further treatment had longer PFS, compared with patients in the watchful waiting group (p = 0.011). Bilateral involvement at diagnosis was associated with significantly inferior PFS (p = 0.029), whereas age, IPI score, or TNM staging were not associated with PFS. No serious adverse reaction was reported among patients with further treatment. Conclusions Bilateral involvement was associated with poor prognosis. Among patients with residual lesions after surgery, further treatment was associated with improved survival. Patients with OAML might experience disease progression or relapse more than five years after initial treatment. Bilateral involvement was associated with a poor prognosis of OAML and call for extended surveillance of disease progression for patients with bilateral involvement. Among patients with residual lesions after surgical treatment, further consolidation treatment could lead to improved survival, compared with watchful waiting. Systemic treatment might be considered as a treatment candidate, given the noted rare adverse event.

Background. Diffuse large B cell lymphoma (DLBCL) is a life-threatening malignant tumor characterized by heterogeneous clinical, phenotypic, and molecular manifestations. Given the association between immunity and tumors, identifying a suitable immune biomarker could improve DLBCL diagnosis. Methods. We systematically searched for DLBCL gene expression microarray datasets from the GEO database. Immune-related genes (IRGs) were obtained from the ImmPort database, and 318 transcription factor (TF) targets in cancer were retrieved from the Cistrome Cancer database. An immune-related classifier for DLBCL prognosis was constructed using Cox regression and LASSO analysis. To assess differences in overall survival between the low- and high-risk groups, we analyzed the tumor microenvironment (TME) and immune infiltration in DLBCL using the ESTIMATE and CIBERSORT algorithms. WGCNA was applied to study the molecular mechanisms explaining the clinical significance of our immune-related classifier and TFs. Results. Eighteen IRGs were selected to construct the classifier. The multi-IRG classifier showed powerful predictive ability. Patients with a high-risk score had poor survival. Based on the AUC for three- and five-year survival, the classifier exhibited better predictive power than clinical data. Discrepancies in overall survival between the low- and high-risk score groups might be explained by differences in immune infiltration, TME, and transcriptional regulation. Conclusions. Our study describes a novel prognostic IRG classifier with strong predictive power in DLBCL. Our findings provide valuable guidance for further analysis of DLBCL pathogenesis and clinical treatment.

Chimeric antigen receptor T (CAR-T) cell therapy has demonstrated remarkable efficacy in relapsed/refractory large B-cell lymphoma (R/R LBCL), yet nearly 40-60% of patients fail to achieve durable responses. The mechanisms underlying interpatient variability in CAR-T expansion and persistence remain incompletely understood. In this exploratory study, we preliminarily investigated the associations between baseline peripheral blood immune subsets, CAR-T expansion kinetics, and clinical outcomes. We retrospectively analyzed 33 patients with R/R LBCL who received CD19/CD22 bispecific chimeric antigen receptor T-cell therapy (CAR2219) at our center. Peripheral blood samples were analyzed by flow cytometry. CAR-T cell expansion was monitored longitudinally, and group-based trajectory modeling (GBTM) classified patients into expansion patterns. Associations with progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan-Meier analysis and Cox regression. Twenty-two patients received tislelizumab (a PD-1 inhibitor) as maintenance therapy (200 mg intravenously every 3 weeks) starting on day 28 after CAR-T infusion. This regimen was not used as prior therapy, bridging therapy, or co-infusion, rather, it was designed to potentially enhance CAR-T persistence after the initial expansion phase. Given the small sample size (n = 33) and the exploratory nature of the analyses, all findings are hypothesis-generating only and require validation in large prospective cohorts. Two distinct CAR-T expansion trajectories were identified: a low-expansion group (Group 1, n = 18) and a high-expansion group (Group 2, n = 15). Compared to Group 1, Group 2 exhibited higher peak expansion (Cmax, p < 0.001), greater total exposure (area under the curve (AUC), p < 0.001), and delayed time to peak (Tmax, 14 days vs. 10 days). Group 2 had higher baseline naive T cells (FDR-adjusted p = 0.024), helper T cells (FDR-adjusted p = 0.006), and CD4/CD8 ratio (FDR-adjusted p = 0.049), and fewer activated regulatory T cells (Tregs) (FDR-adjusted p = 0.018). Higher CD4/CD8 ratio associated with longer PFS (HR 0.41, 95% CI 0.17-0.73, p = 0.047). In exploratory subgroup analyses, a directional trend toward longer PFS was noted among patients with high baseline PD-1 expression who received PD-1 inhibitor maintenance therapy, whereas no such trend was observed in those without maintenance. These hypothesis-generating observations require validation in larger prospective cohorts. Baseline immune cell composition may associate with CAR-T expansion and outcomes in R/R LBCL. Exploratory subgroup analyses suggested that the direction of association between baseline PD-1 expression and PFS may differ according to receipt of PD-1 inhibitor maintenance therapy (initiated on day 28 post-infusion), though no statistical significance was reached in either subgroup. Current evidence does not support the clinical use of baseline PD-1 expression as a predictive biomarker, and further validation in prospective studies is warranted.

Osteoporosis is a serious public bone metabolic disease. However, the mechanisms underlying bone loss combined with ageing, which is known as senile osteoporosis, remains unknown. Here we show the detailed phenotype of this disease caused by SIRT6 knock out （KO） in mice. To the best of our knowledge, this is the first study to reveal that SIRT6 is expressed in both bone marrow stroma cells and bone-related cells in both mouse and human models, which suggests that SIRT6 is an important regulator in bone metabolism. SIRT6-KO mice exhibit a significant decrease in body weight and remarkable dwarfism. The skeleton of the SIRT6-KO mouse is deficient in cartilage and mineralized bone tissue. Moreover, the osteocalcin concentration in blood is lower, which suggests that bone mass is markedly lost. Besides, the tartrate-resistant acid phosphatase 5b （TRAP5b） concentration is much higher, which suggests that bone resorption is overactive. Both trabecular and cortical bones exhibit severe osteopenia, and the bone mineral density is decreased. Moreover, double-labelling analysis shows that bone formation is much slower. To determine whether SIRT6 directly regulates bone metabolism, we cultured primary bone marrow stromal cells for osteogenesis and osteoclastogenesis separately to avoid indirect interference in vivo responses such as inflammation. Taken together, these results show that SIRT6 can directly regulate osteoblast proliferation and differentiation, resulting in attenuation in mineralization. Furthermore, SIRT6 can directly regulate osteoclast differentiation and results in a higher number of small osteoclasts, which may be related to overactive bone resorption.

Breast cancer is the most prevalent malignancy among women. Doxorubicin (Dox) resistance was one of the major obstacles to improving the clinical outcome of breast cancer patients. The purpose of this study was to investigate the relationship between the FABP signaling pathway and Dox resistance in breast cancer. The resistance property of MCF-7/ADR cells was evaluated employing CCK-8, Western blot (WB), and confocal microscopy techniques. The glycolipid metabolic properties of MCF-7 and MCF-7/ADR cells were identified using transmission electron microscopy, PAS, and Oil Red O staining. FABP5 and CaMKII expression levels were assessed through GEO and WB approaches. The intracellular calcium level was determined by flow cytometry. Clinical breast cancer patient’s tumor tissues were evaluated by immunohistochemistry to determine FABP5 and p-CaMKII protein expression. In the presence or absence of FABP5 siRNA or the FABP5-specific inhibitor SBFI-26, Dox resistance was investigated utilizing CCK-8, WB, and colony formation methods, and intracellular calcium level was examined. The binding ability of Dox was explored by molecular docking analysis. The results indicated that the MCF-7/ADR cells we employed were Dox-resistant MCF-7 cells. FABP5 expression was considerably elevated in MCF-7/ADR cells compared to parent MCF-7 cells. FABP5 and p-CaMKII expression were increased in resistant patients than in sensitive individuals. Inhibition of the protein expression of FABP5 by siRNA or inhibitor increased Dox sensitivity in MCF-7/ADR cells and lowered intracellular calcium, PPARγ, and autophagy. Molecular docking results showed that FABP5 binds more powerfully to Dox than the known drug resistance-associated protein P-GP. In summary, the PPARγ and CaMKII axis mediated by FABP5 plays a crucial role in breast cancer chemoresistance. FABP5 is a potentially targetable protein and therapeutic biomarker for the treatment of Dox resistance in breast cancer.

Accurate downhole depth measurement is essential for oil and gas well operations, directly influencing reservoir contact, production efficiency, and operational safety. Collar correlation using a casing collar locator (CCL) is fundamental for precise depth calibration. While neural network has achieved significant progress in collar recognition, preprocessing methods for such applications remain underdeveloped. Moreover, the limited availability of real well data poses substantial challenges for training neural network models that require extensive datasets. This paper presents a system integrated into a downhole toolstring for CCL log acquisition to facilitate dataset construction. Comprehensive preprocessing methods for data augmentation are proposed, and their effectiveness is evaluated using baseline neural network models. Through systematic experimentation across diverse configurations, the contribution of each augmentation method is analyzed. Results demonstrate that standardization, label distribution smoothing (LDS), and random cropping are fundamental prerequisites for model training, while label smoothing regularization (LSR), time scaling, and multiple sampling significantly enhance model generalization capabilities. Incorporating the proposed augmentation methods into the two baseline models results in maximum F1 score improvements of 0.027 and 0.024 for the TAN and MAN models, respectively. Furthermore, applying these techniques yields F1 score gains of up to 0.045 for the TAN model and 0.057 for the MAN model compared to prior studies. Performance evaluation on real CCL waveforms confirms the effectiveness and practical applicability of our approach. This work addresses the existing gaps in data augmentation methodologies for training casing collar recognition models under CCL data-limited conditions, and provides a technical foundation for the future automation of downhole operations.

We present a dynamics study toward the G326.611+0.811 (G326) hub–filament system (HFS) cloud using new APEX observations of both 13CO and C18O (J = 2–1). The G326 HFS cloud constitutes a central hub and at least four hub-composing filaments that are divided into a major branch of filaments (F1 and F2) and a side branch (F3–F5). The cloud holds ongoing high-mass star formation as characterized by three massive dense clumps (i.e., 370–1100 M ⊙ and 0.14–0.16 g cm−2 for C1–C3) with high clump-averaged mass infalling rates (>10−3 M ⊙ yr−1) within the major filament branch, and the associated point sources bright at 70 μm, typical of young protostars. Along the five filaments, velocity gradients are found in both 13CO and C18O (J = 2–1) emission, suggesting that filament-aligned gravitational collapse toward the central hub (i.e., C2) is responsible for the high-mass star formation therein. Moreover, a periodic velocity oscillation along the major filament branch is revealed in both 13CO and C18O (J = 2–1) emission with a characteristic wavelength of ∼3.5 pc and an amplitude of ∼0.31–0.38 km s−1. We suggest that this pattern of velocity oscillation in G326 could arise from clump-forming gas motion induced by gravitational instabilities. The prevalent velocity gradients, fragmentation of the major branch of filaments, and the ongoing collapse of the three massive dense clumps are indicative that G326 is an HFS undergoing global collapse.

* A Passive Aeration Ditch was developed to treat decentralized wastewater. * A model was developed to describe the process performance. * A high C/N ratio facilitates microbial growth but nitrification deteriorates. * A high salinity decreases both organic and nitrogen contaminants removal. Decentralized wastewater containing elevated salinity is an emerging threat to the local environment and sanitation in remote coastal communities. Regarding the cost and treatment efficiencies, we propose a passive aeration ditch (PAD) using non-woven polyester fabric as a feasible bubbleless aerator and biofilm carrier for wastewater treatment. Consideration has been first given to PAD's efficacy in treating saline decentralized wastewater, and then to the impact of chemical oxygen demand-to-nitrogen (C/N) ratio and salinity on biofilm formation. A multispecies model incorporating the salinity effect has been developed to depict the system performance and predict the microbial community. Results showed that the PAD system had great capacity for pollutants removal. The biofilm thickness increased at a higher C/N ratio because of the boost of aerobic heterotrophs and denitrifying bacteria, which consequently improved the COD and total nitrogen removal. However, this led to the deterioration of ammonia removal. Moreover, while a higher salinity benefited the biofilm growth, the contaminant removal efficiencies decreased because the salinity inhibited the activity of aerobic heterotrophs and reduced the abundance of nitrifying bacteria inside the biofilm. Based on the model simulation, feed water with salinity below 2% and C/N ratio in a range of 1 to 3 forms a biofilm that can reach relatively high organic matter and ammonia removal. These findings not only show the feasibility of PAD in treatment of saline decentralized wastewater, but also offer a systematic strategy to predict and optimize the process performance.