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This paper aims to propose a new multi-attribute decision making (MADM) method in complicated and fuzzy decision-making environment. To express both decision makers (DMs’) quantitative and qualitative evaluation information comprehensively and consider their high hesitancy in giving their assessment values in MADM process, we combine q-rung dual hesitant fuzzy sets (q-RDHFSs) with uncertain linguistic variables and develop a new tool, called the q-rung dual hesitant uncertain linguistic sets (q-RDHULSs). First, the definition, operations and comparison method of q-RDHULSs are proposed. Second, given the interrelationship among multiple q-rung dual hesitant uncertain linguistic variables (q-RDHULVs) we introduce some aggregation operators (AOs) to fuse q-rung dual hesitant uncertain linguistic (q-RDHUL) information based on the Muirhead mean, i.e. the q-RDHUL Muirhead mean operator, the q- RDHUL weighted Muirhead mean operator, the q-RDHUL dual Muirhead mean operator, and the q-RDHUL weighted dual Muirhead mean operator. To cope with MADM problems with q-RDHUL information, we propose a new method based on the proposed AOs. Afterwards, we apply the proposed method to an enterprise informatization level evaluation problem to verify its effectiveness. In addition, we also explain why our proposed method is more powerful and flexible than others.

As Chinese shows both satellite- and verb-framed properties (Slobin, 2004; Talmy, 2012, 2016), it provides a unique lens through which to observe the extent of first-language (L1) typological influence in second language (L2) acquisition of motion expressions. This study has dual purposes. First, it extends Wu's (2016) investigation on motion expressions produced by 80 L1 satellite-framed English learners of L2 Chinese to include newly collected data produced by L1 verb-framed speakers, a sample comprised of 41 L1 Japanese learners of Chinese and 40 Japanese native speakers. Second, it synthesizes the data from both studies and comprehensively examines factors that have been proposed to affect development of L2 thinking-for-speaking (TFS) patterns. The results show that development of L2 TFS is best predicted by learners' L1 type, but the effect is mitigated by L2 proficiency. While the L1 English learners outperform L1 Japanese learners in their development of target-like L2 Chinese TFS, learners with limited L2 proficiency in both groups tend to adopt verb-framed strategies to express only the core path information of a motion event and leave out the manner details. Analysis of L1 Japanese learners' oral narratives in L1 Japanese and L2 Chinese also shows that reverse L2-to-L1 transfer is less likely to happen when learning a typologically closer L2 that requires minimal restructuring of their L1 TFS.

Abstract The objective of this study is to investigate the effects of various doses of esketamine on the median effective concentration (EC50) of propofol required for inhibiting body movement during hysteroscopy. Additionally, this research aims to explore the pharmacodynamic interactions between esketamine and propofol. Prospective, double-blind, up-down sequential allocation study. Operating room, post-anesthesia care unit (PACU), and general ward. A total of 90 patients were allocated into three groups in a randomized, double-blinded manner as follows: 0.1 mg/kg esketamine combined with propofol intravenous injection (EP0.1) group, 0.2 mg/kg esketamine combined with propofol intravenous injection (EP0.2) group, 0.3 mg/kg esketamine combined with propofol of intravenous injection (EP0.3) group. For the initial patient in each group, the starting effector target concentration of propofol was set at 4 µg/ml. Each patient received an initial intravenous injection of 0.04 mg/kg midazolam, followed by the administration of the appropriate dose of esketamine. Ten seconds after the esketamine injection, propofol was administered intravenously to achieve the target concentration. In accordance with the sequential method principle, the concentration of propofol for the subsequent patient was adjusted based on the response of the previous patient. Effective inhibition of body movement was defined as the absence of any involuntary body movements throughout the entire surgical process. If the previous patient exhibited body movements, the propofol concentration for the next patient was increased by 0.5 µg/ml; conversely, if no movements were observed, it was decreased by 0.5 µg/ml. The up-down sequential allocation method and probit regression were used to calculate the EC50 of propofol. Hospital Anxiety and Depression Scale-Anxiety (HADS-A) and Depression (HADS-D) score, adverse events, hemodynamic changes, demographic data and clinical characteristics. The EC50 of propofol was 3.849 μg/ml (95% CI: 3.419–4.281) in the EP0.1 group, 3.641 μg/ml (95% CI: 2.807−4.200) in the EP0.2 group, and 3.417 μg/ml (95% CI: 2.845–3.852) in the EP0.3 group. These findings suggest that esketamine can dose-dependently reduce the EC50 of propofol. Esketamine can dose-dependently reduce the EC50 of propofol in hysteroscopy, while concurrently lowering patients’ HADS-A and HADS-D scores 24 h post-operation. It is concluded that the optimal dose of esketamine, when combined with propofol for hysteroscopy, is 0.3 mg/kg.

Abstract Excessive oxidative response, unbalanced immunomodulation, and impaired mesenchymal stem cell function in periodontitis in diabetes makes it a great challenge to achieve integrated periodontal tissue regeneration. Here, a polyphenol-mediated redox-active algin/gelatin hydrogel encapsulating a conductive poly(3,4-ethylenedioxythiopene)-assembled polydopamine-mediated silk microfiber network and a hydrogen sulfide sustained-release system utilizing bovine serum albumin nanoparticles is developed. This hydrogel is found to reverse the hyperglycemic inflammatory microenvironment and enhance functional tissue regeneration in diabetic periodontitis. Polydopamine confers the hydrogel with anti-oxidative and anti-inflammatory activity. The slow, sustained release of hydrogen sulfide from the bovine serum albumin nanoparticles recruits mesenchymal stem cells and promotes subsequent angiogenesis and osteogenesis. Moreover, poly(3,4-ethylenedioxythiopene)-assembled polydopamine-mediated silk microfiber confers the hydrogel with good conductivity, which enables it to transmit endogenous bioelectricity, promote cell arrangement, and increase the inflow of calcium ion. In addition, the synergistic effects of hydrogen sulfide gaseous-bioelectric coupling promotes bone formation by amplifying autophagy in periodontal ligament stem cells and modulating macrophage polarization via lipid metabolism regulation. This study provides innovative insights into the synergistic effects of conductivity, reactive oxygen species scavenging, and hydrogen sulfide on the periodontium in a hyperglycemic inflammatory microenvironment, offering a strategy for the design of gaseous-bioelectric biomaterials to promote functional tissue regeneration in immune-related diseases.

Abstract Background This study aimed at investigating the relationship between the weekend catch-up outdoor duration (WCOD) and prevalence of myopia among students in China. Methods This cross-sectional study recruited participants in 107 schools (six cities, 30 districts) from China from May to June 2021. Demographic characteristics (age, grade, sex, ethnicity, BMI, resident, and parents’ myopia), optically habits (bad writing habits, working/studying time per day, continuous working/studying time per day, and screen time per day) and outdoor duration (weekday and weekend) were obtained from questionnaire. WCOD was defined as outdoor time 1 h longer on weekends than on weekdays. Spherical equivalent (SE) of refractive error were measured with non-cycloplegic refraction. Adjusted multivariate logistic regression analysis was performed to evaluate the relationship between WCOD and prevalence of myopia. Results Students with myopia had shorter WCOD compared with those without myopia (P

Abstract For the multistage progression of prostate cancer (PCa) and resistance to immunotherapy, tumour‐associated macrophage is an essential contributor. Although immunotherapy is an important and promising treatment modality for cancer, most patients with PCa are not responsive towards it. In addition to exploring new therapeutic targets, it is imperative to identify highly immunotherapy‐sensitive individuals. This research aimed to establish a signature risk model, which derived from the macrophage, to assess immunotherapeutic responses and predict prognosis. Data from the UCSC‐XENA, GEO and TISCH databases were extracted for analysis. Based on both single‐cell datasets and bulk transcriptome profiles, a macrophage‐related score (MRS) consisting of the 10‐gene panel was constructed using the gene set variation analysis. MRS was highly correlated with hypoxia, angiogenesis, and epithelial‐mesenchymal transition, suggesting its potential as a risk indicator. Moreover, poor immunotherapy responses and worse prognostic performance were observed in the high‐MRS group of various immunotherapy cohorts. Additionally, APOE, one of the constituent genes of the MRS, affected the polarisation of macrophages. In particular, the reduced level of M2 macrophage and tumour progression suppression were observed in PCa xenografts which implanted in Apolipoprotein E‐knockout mice. The constructed MRS has the potential as a robust prognostic prediction tool, and can aid in the treatment selection of PCa, especially immunotherapy options.

Abstract Precise survival risk stratification is crucial for personalized therapy in bladder cancer (BCa). This study developed and validated an end-to-end deep learning system using histological slides to predict overall survival (OS) risk in BCa patients. We employed the BlaPaSeg tile classifier to generate tissue probability heatmaps and segmentation maps, trained two prognostic networks, MacroVisionNet and UniVisionNet, and explored six potential BCa prognostic biomarkers. Across all cohorts, the AUC for BlaPaSeg ranged from 0.9906 to 0.9945, while the C-index varied from 0.655 to 0.834 for MacroVisionNet and 0.661 to 0.853 for UniVisionNet. After covariate adjustment, the hazard ratio (HR) values for high-risk groups were 1.97 to 5.06 in MacroVisionNet and 2.13 to 4.01 in UniVisionNet. The high-risk Coloc (Tumor Co-localization score) and IMTS (Integrated Muscle Tumor Score) groups illustrated a higher death risk with HR values from 1.41 to 10.16. The system improves BCa survival prediction and supports refined patient management.

Abstract Alternative splicing is an important process that contributes to highly diverse transcripts and protein products, which can affect the development of disease in various organisms. Cardiovascular disease (CVD) represents one of the greatest global threats to humans, particularly acute myocardial infarction (MI) and subsequent ischemic reperfusion (IR) injury, which involve complex transcriptomic changes in heart tissues associated with metabolic reshaping and immunological response. In this study, we used a newly developed ONT full-length transcriptomic approach and performed transcript-resolved differential expression profiling in murine models of MI and IR. We built an analytical pipeline to reliably identify and quantify alternative splicing products (isoforms), expanding on the currently available catalog of isoforms described in mice. The updated alternative splicing landscape included transcripts, genes, and pathways that were differentially regulated during IR and MI. Our study establishes a pipeline to profile highly diverse isoforms using state-of-the-art long-read sequencing, builds a landscape of alternative splicing in the mouse heart during MI and IR.

Abstract Background Long-term care insurance (LTCI) is essential to alleviate the challenges of rapid aging. Research on LTCI in developing countries is limited and conclusions remain controversial. This study aims to empirically evaluate how the LTCI pilot in selected cities influences healthcare utilization and expenditures among middle-aged and older Chinese adults. Methods Data was from 2013, 2015, and 2018 China Health and Retirement Longitudinal Study. 167 LTCI and 8225 non-LTCI group participants were identified. Propensity score matching difference-in-difference method was used to evaluate the net effect of LTCI. The robustness of the findings was tested using a placebo test. Results In the pilot cities, around 17.8% of the population had LTCI coverage, with approximately 59.9% participating in urban employee medical insurance and 81.4% being urban residents. LTCI significantly reduced the monthly out-of-pocket outpatient expenditure by 313.764 yuan (P

Abstract Neuroimaging studies have revealed that the mechanisms of auditory hallucinations are related to morphological changes in multiple cortical regions, but studies on brain network properties are lacking. This study aims to construct intra-individual structural covariance networks and reveal network changes related to auditory hallucinations. T1-weighted MRI images were acquired from 90 schizophrenia patients with persistent auditory hallucinations (pAH group), 55 schizophrenia patients without auditory hallucinations (non-pAH group), and 83 healthy controls (HC group). Networks were constructed using the voxel-based gray matter volume and the intra-individual structural covariance was based on the similarity between the morphological variations of any two regions. One-way ANCOVA was employed to compare global and local network metrics among the three groups, and edge analysis was conducted via network-based statistics. In the pAH group, Pearson correlation analysis between network metrics and clinical symptoms was conducted. Compared with the HC group, both the pAH group (p = 0.01) and the non-pAH group (p = 3.56 × 10−4) had lower nodal efficiency of the left medial superior frontal gyrus. Compared to the non-pAH group and HC group, the pAH group presented lower nodal efficiency of the temporal pole of the left superior temporal gyrus (p = 1.09 × 10−3; p = 7.67 × 10−4) and right insula (p = 0.02; p = 8.99 × 10−6), and lower degree centrality of the right insula (p = 0.04; p = 1.65 × 10−5). The pAH group had a subnetwork with reduced structural covariance centered by the left temporal pole of the superior temporal gyrus. In the pAH group, the normalized clustering coefficient (r = −0.36, p = 8.45 × 10−3) and small-worldness (r = −0.35, p = 9.89 × 10−3) were negatively correlated with the PANSS positive scale score. This study revealed network changes in schizophrenia patients with persistent auditory hallucinations, and provided new insights into the structural architecture related to auditory hallucinations at the network level.

Abstract Esophageal squamous cell carcinoma (ESCC) is highly heterogeneous. Our understanding of full molecular and immune landscape of ESCC remains limited, hindering the development of personalised therapeutic strategies. To address this, we perform genomic-transcriptomic characterizations and AI-aided histopathological image analysis of 120 Chinese ESCC patients. Here we show that ESCC can be categorized into differentiated, metabolic, immunogenic and stemness subtypes based on bulk and single-cell RNA-seq, each exhibiting specific molecular and histopathological features based on an amalgamated deep-learning model. The stemness subgroup with signature genes, such as WFDC2, SFRP1, LGR6 and VWA2, has the poorest prognosis and is associated with downregulated immune activities, a high frequency of EP300 mutation/activation, functional mutation enrichment in Wnt signalling and the highest level of intratumoural heterogeneity. The immune profiling by transcriptomics and immunohistochemistry reveals ESCC cells overexpress natural killer cell markers XCL1 and CD160 as immune evasion. Strikingly, XCL1 expression also affects the sensitivity of ESCC cells to common chemotherapy drugs. This study opens avenues for ESCC treatment and provides a valuable public resource to better understand ESCC.

Abstract All-optical nonlinear activation functions (NAFs) are crucial for enabling rapid optical neural networks (ONNs). As linear matrix computation advances in integrated ONNs, on-chip all-optical NAFs face challenges such as limited integration, high latency, substantial power consumption, and a high activation threshold. In this work, we develop an integrated nonlinear optical activator based on the butt-coupling integration of two-dimensional (2D) MoTe2 and optical waveguides (OWGs). The activator exhibits an ultra-broadband response from visible to near-infrared wavelength, a low activation threshold of 0.94 μW, a small device size (~50 µm2), an ultra-fast response rate (2.08 THz), and high-density integration. The excellent nonlinear effects and broadband response of 2D materials have been utilized to create all-optical NAFs. These activators were applied to simulate MNIST handwritten digit recognition, achieving an accuracy of 97.6%. The results underscore the potential application of this approach in ONNs. Moreover, the classification of more intricate CIFAR-10 images demonstrated a generalizable accuracy of 94.6%. The present nonlinear activator promises a general platform for three-dimensional (3D) ultra-broadband ONNs with dense integration and low activation thresholds by integrating a variety of strong nonlinear optical (NLO) materials (e.g., 2D materials) and OWGs in glass.

Abstract Background Concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced esophageal squamous cell carcinoma (ESCC). However, the optimal radiotherapy regimen, particularly in terms of total dose and planned range of irradiation field, remains unclear. This phase III clinical trial aimed to compare the survival benefits between different radiation doses and different target fields. Methods This trial compared two aspects of radiation treatment, total dose and field, using a two‐by‐two factorial design. The high‐dose (HD) group received 59.4 Gy radiation, and the standard‐dose (SD) group received 50.4 Gy. The involved field irradiation (IFI) group and elective nodal irradiation (ENI) group adopted different irradiation ranges. The participants were assigned to one of the four groups (HD+ENI, HD+IFI, SD+ENI and SD+IFI). The primary endpoint was overall survival (OS), and the secondary endpoints included progression‐free survival (PFS). The synergy indexwas used to measure the interaction effect between dose and field. Results The interaction analysis did not reveal significant synergistic effects between the dose and irradiation field. In comparison to the target field, patients in IFI or ENI showed similar OS (hazard ratio [HR] = 0.99, 95% CI: 0.80‐1.23, p = 0.930) and PFS (HR = 1.02, 95% CI: 0.82–1.25). The HD treatment did not show significantly prolonged OS compared with SD (HR = 0.90, 95% CI: 0.72–1.11, p = 0.318), but it suggested improved PFS (25.2 months to 18.0 months). Among the four groups, the HD+IFI group presented the best survival, while the SD+IFI group had the worst prognosis. No significant difference in the occurrence of severe adverse events was found in dose or field comparisons. Conclusions IFI demonstrated similar treatment efficacy to ENI in CCRT of ESCC. The HD demonstrated improved PFS, but did not significantly improve OS. The dose escalation based on IFI (HD+IFI) showed better therapeutic efficacy than the current recommendation (SD+ENI) and is worth further validation.

Abstract Recently in diagnosis of Aortic dissection (AD), the synthesis of contrast enhanced CT (CE-CT) images from non-contrast CT (NC-CT) images is an important topic. Existing methods have achieved some results but are unable to synthesize a continuous and clear intimal flap on NC-CT images. In this paper, we propose a multi-stage cascade generative adversarial network (MCGAN) to explicitly capture the features of the intimal flap for a better synthesis of aortic dissection images. For the intimal flap with variable shapes and more detailed features, we extract features in two ways: dense residual attention blocks (DRAB) are integrated to extract shallow features and UNet is employed to extract deep features; then deep features and shallow features are cascaded and fused. For incomplete flaps or lack of details, we use spatial attention and channel attention to extract key features and locations. At the same time, multi-scale fusion is used to ensure the continuity of the intimal flap. We perform the experiment on a set of 124 patients (62 with AD and 62 without AD). The evaluation results show that the synthesized images have the same characteristics as the real images and achieves better results than the popular methods.

Abstract Maintaining quantum coherence and entanglement in the presence of environmental noise, particularly within non-Markovian contexts, represents a significant challenge for the progression of quantum information science and technology. This study offers a substantial advancement by investigating the dynamics of a two-qubit system subjected to diverse noise conditions, encompassing relaxation, dephasing, and their cumulative effects. By employing quantum-state-diffusion equations specifically crafted for non-Markovian environments, we introduce an innovative strategy to counteract the detrimental influences of environmental noise on quantum teleportation fidelity and entanglement concurrence. Our results underscore the potential for external interventions to markedly improve the resilience of quantum information processing tasks over prolonged durations, especially in settings where dephasing noise prevails. A key revelation is the intricate relationship between dephasing noise and the initial state of entanglement, which profoundly impacts the occurrence of entanglement sudden death. This research not only deepens our comprehension of quantum system dynamics under noisy circumstances but also furnishes practical directives for engineering robust quantum systems, a necessity for the development of scalable quantum technologies.

Abstract Background Arginase is abundantly expressed in colorectal cancer and disrupts arginine metabolism, promoting the formation of an immunosuppressive tumor microenvironment. This significant factor contributes to the insensitivity of colorectal cancer to immunotherapy. Tumor-associated macrophages (TAMs) are major immune cells in this environment, and aberrant arginine metabolism in tumor tissues induces TAM polarization toward M2-like macrophages. The natural compound piceatannol 3ʹ-O-glucoside inhibits arginase activity and activates nitric oxide synthase, thereby reducing M2-like macrophages while promoting M1-like macrophage polarization. Methods The natural compounds piceatannol 3ʹ-O-glucoside and indocyanine green were encapsulated within microparticles derived from tumor cells, termed PG/ICG@MPs. The enhanced cancer therapeutic effect of PG/ICG@MP was assessed both in vitro and in vivo. Results PG/ICG@MP precisely targets the tumor site, with piceatannol 3ʹ-O-glucoside concurrently inhibiting arginase activity and activating nitric oxide synthase. This process promotes increased endogenous nitric oxide production through arginine metabolism. The combined actions of nitric oxide and piceatannol 3ʹ-O-glucoside facilitate the repolarization of tumor-associated macrophages toward the M1 phenotype. Furthermore, the increase in endogenous nitric oxide levels, in conjunction with the photodynamic effect induced by indocyanine green, increases the quantity of reactive oxygen species. This dual effect not only enhances tumor immunity but also exerts remarkable inhibitory effects on tumors. Conclusion Our research results demonstrate the excellent tumor-targeting effect of PG/ICG@MPs. By modulating arginine metabolism to improve the tumor immune microenvironment, we provide an effective approach with clinical translational significance for combined cancer therapy.

Background: Currently, the need for new therapeutic strategies involving programmed cell death protein-1 (PD-1) monoclonal antibodies in the second-line setting of small cell lung cancer (SCLC) is urgent. This study aimed to evaluate the efficacy and safety of anlotinib plus penpulimab as a second-line treatment for patients with SCLC who progressed after first-line platinum-based chemotherapy. Methods: This study included the patients from Cohort 4 of a single-arm, open-label, multicenter, phase II clinical trial. A safety run-in phase was performed under anlotinib (10/12 mg quaque die [QD], days 1–14) plus penpulimab (200 mg intravenously [IV], day 1) in a 21-day cycle, followed by the formal trial in which the patients received anlotinib (12 mg QD, days 1–14) plus penpulimab (200 mg IV, day 1) in a 21-day cycle. The primary endpoint of the safety run-in phase was safety. The primary endpoint of the formal trial phase was the objective response rate (ORR). Results: From April 28, 2020, to November 24, 2020, 21 patients were enrolled from 11 hospitals, including 2 in the safety run-in phase and 19 in the formal trial phase. In the formal trial phase, the ORR was 42.1% (8/19; 95% confidence interval [CI]: 17.7–66.6%). The median progression-free survival was 4.8 months (95% CI: 2.9–11.3 months), and the median overall survival was 13.0 months (95% CI: 4.6–not applicable [NA] months). The incidence of ≥grade 3 treatment-related adverse events (TRAEs) was 52.4% (11/21), and the incidence of treatment-related serious adverse events (AEs) was 28.6% (6/21). Two AE-related deaths occurred. The most common AEs were hypertension (57.1%, 12/21), hypothyroidism (42.9%, 9/21), and hypertriglyceridemia (38.1%, 8/21). Conclusions: In patients with SCLC who progressed after first-line platinum-based chemotherapy, the second-line anlotinib plus penpulimab treatment demonstrates promising anti-cancer activity and a manageable safety profile, which warrants further investigation. Trial registration: No. NCT04203719, https://clinicaltrials.gov/.

Abstract Background Lavandula angustifolia holds importance as an aromatic plant with extensive applications spanning the fragrance, perfume, cosmetics, aromatherapy, and spa sectors. Beyond its aesthetic and sensory applications, this plant offers medicinal benefits as a natural herbal remedy and finds use in household cleaning products. While extensive genomic data, inclusive of plastid and nuclear genomes, are available for this species, researchers have yet to characterize its mitochondrial genome. This gap in knowledge hampers deeper understanding of the genome organization and its evolutionary significance. Results Through the course of this study, we successfully assembled and annotated the mitochondrial genome of L. angustifolia, marking a first in this domain. This assembled genome encompasses 61 genes, which comprise 34 protein-coding genes, 24 transfer RNA genes, and three ribosomal RNA genes. We identified a chloroplast sequence insertion into the mitogenome, which spans a length of 10,645 bp, accounting for 2.94% of the mitogenome size. Within these inserted sequences, there are seven intact tRNA genes (trnH-GUG, trnW-CCA, trnD-GUC, trnS-GGA, trnN-GUU, trnT-GGU, trnP-UGG) and four complete protein-coding genes (psbA, rps15, petL, petG) of chloroplast derivation. Additional discoveries include 88 microsatellites, 15 tandem repeats, 74 palindromic repeats, and 87 forward long repeats. An RNA editing analysis highlighted an elevated count of editing sites in the cytochrome c oxidase genes, notably ccmB with 34 editing sites, ccmFN with 32, and ccmC with 29. All protein-coding genes showed evidence of cytidine-to-uracil conversion. A phylogenetic analysis, utilizing common protein-coding genes from 23 Lamiales species, yielded a tree with consistent topology, supported by high confidence values. Conclusions Analysis of the current mitogenome resource revealed its typical circular genome structure. Notably, sequences originally from the chloroplast genome were found within the mitogenome, pointing to the occurrence of horizontal gene transfer between organelles. This assembled mitogenome stands as a valuable resource for subsequent studies on mitogenome structures, their evolution, and molecular biology.

Abstract Glioblastoma (GBM) is the most common primary intracranial malignant tumor. Recent literature suggests that induction of programmed death has become a mainstream cancer treatment strategy, with ferroptosis being the most widely studied mode. Complement C5a receptor 1 (C5aR1) is associated with both tumorigenesis and tumor-related immunity. However, knowledge regarding the role of C5aR1 in GBM progression is limited. In the present study, we observed significant upregulation of C5aR1 in glioma tissue. In addition, C5aR1 expression was found to be closely associated with patient prognosis and survival. Subsequent experimental verification demonstrated that C5aR1 promoted the progression of GBM mainly by suppressing ferroptosis induction, inhibiting the accumulation of lipid peroxides, and stabilizing the expression of the core antiferroptotic factor glutathione peroxidase 4 (GPX4). Aberrant N6-methyladenosine (m6A) modification of GPX4 mRNA contributes significantly to epigenetic tumorigenesis, and here, we report that selective methyltransferase-like 3 (METTL3)-dependent m6A methylation of GPX4 plays a key role in C5AR1 knockdown-induced ferroptosis induction. Mechanistically, ERK1/2 signaling pathway activation increases the METTL3 protein abundance in GBM cells. This activation then increases the stability of METTL3-mediated m6A modifications on GPX4, enabling it to fulfill its transcriptional function. More importantly, in an intracranial xenograft mouse model, PMX205, a C5aR1 inhibitor, promoted alterations in ferroptosis in GBM cells and inhibited GBM progression. In conclusion, our findings suggest that C5aR1 inhibits ferroptosis in GBM cells and promotes MettL3-dependent GPX4 expression through ERK1/2, thereby promoting glioma progression. Our study reveals a novel mechanism by which the intracellular complement receptor C5aR1 suppresses ferroptosis induction and promotes GBM progression. These findings may facilitate the identification of a potential therapeutic target for glioma.

Abstract Radiotherapy (RT) is a crucial treatment for colorectal cancer (CRC) patients, but it often fails to induce systemic antitumor immunity. CD73, an immunomodulatory factor, is upregulated after RT and associated with poor prognosis in CRC patients. This study aims to elucidate the mechanisms driving RT-induced CD73 upregulation in CRC and investigate how combining RT with CD73 blockade stimulates immune responses and induces abscopal effects. Findings revealed that RT-induced CD73 upregulation is mediated by the ataxia telangiectasia and Rad3-related (ATR) pathway and correlated with RT tolerance, as demonstrated through flow cytometry, immunofluorescence, and Western Blotting. Using flow cytometry and multicolor immunofluorescence, experiments demonstrated that in CRC subcutaneous tumor models, combination therapy reduces the infiltration of myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), and regulatory T cells (Tregs) while increasing dendritic cells (DCs) and CD8 + T cells, resulting in superior antitumor responses. Additionally, results from flow cytometry, Western Blot, and RNA sequencing demonstrated that combination therapy enhances the antigen-presenting ability of DCs and activates tumor antigen-specific CD8 + T cells, improving their function and delaying their depletion. The activation of the cGAS-STING and IFN-I pathways is crucial for this effect. In summary, the integration of RT with CD73 blockade effectively reverses the immunosuppressive TME and invigorates CD8 + T cell-driven, specific antitumor immune responses. These insights shed fresh light on the mechanisms governing the synergistic modulation of immunity by RT and CD73 blockade in CRC, offering promising avenues for the advancement of therapeutic strategies against CRC.

Abstract Background Severe fever with thrombocytopenia syndrome (SFTS) is a highly fatal infectious disease caused by the SFTS virus (SFTSV), posing a significant public health threat. This study aimed to construct a dynamic model for the early identification of SFTS patients at high risk of disease progression. Methods All eligible patients enrolled between April 2014 and July 2023 were divided into training and validation sets. Thirty-four clinical variables in the training set underwent analysis using least absolute shrinkage and selection operator (LASSO) logistic regression. Selected variables were then input into the multivariate logistic regression model to construct a dynamic nomogram. The model’s performance was assessed using the area under the receiver operating characteristic curve (AUC-ROC), concordance index (C-index), calibration curve, and decision curve analysis (DCA) in both training and validation sets. Kaplan-Meier survival analysis was utilized to evaluate prognostic performance. Results 299 SFTS patients entered the final investigation, with 208 patients in the training set and 90 patients in the validation set. LASSO and the multivariate logistic regression identified six significant prediction factors: age (OR, 1.060; 95% CI, 1.017–1.109; P = 0.007), CREA (OR, 1.017; 95% CI, 1.003–1.031; P = 0.019), PT (OR, 1.765; 95% CI, 1.175–2.752; P = 0.008), D-dimer (OR, 1.039; 95% CI, 1.005–1.078; P = 0.032), nervous system symptoms (OR, 8.244; 95% CI, 3.035–26.858; P

Abstract Uveal melanoma (UM), the primary intraocular tumor in adults, arises from eye melanocytes and poses a significant threat to vision and health. Despite its rarity, UM is concerning due to its high potential for liver metastasis, resulting in a median survival of about a year after detection. Unlike cutaneous melanoma, UM responds poorly to immune checkpoint inhibition (ICI) due to its low tumor mutational burden and PD-1/PD-L1 expression. Tebentafusp, a bispecific T cell engager (TCE) approved for metastatic UM, showed potential in clinical trials, but the objective response rate remains modest. To enhance TCE efficacy, we explored quantitative systems pharmacology (QSP) modeling in this study. By integrating a TCE module into an existing QSP model and using clinical data on UM and tebentafusp, we aimed to identify and rank potential predictive biomarkers for patient selection. We selected 30 important predictive biomarkers, including model parameters and cell concentrations in tumor and blood compartments. We investigated biomarkers using different methods, including comparison of median levels in responders and non-responders, and a cutoff-based biomarker testing algorithm. CD8+ T cell density in the tumor and blood, CD8+ T cell to regulatory T cell ratio in the tumor, and naïve CD4+ density in the blood are examples of key biomarkers identified. Quantification of predictive power suggested a limited predictive power for single pre-treatment biomarkers, which was improved by early on-treatment biomarkers and combination of predictive biomarkers. Ultimately, this QSP model could facilitate biomarker-guided patient selection, improving clinical trial efficiency and UM treatment outcomes.

In this study, we have found two new species—Stropharia subrugosoannulata and Stropharia microaeruginosa. Phylogenetic analyses, based on the internal transcribed spacer regions (ITS) and the nuclear ribosomal RNA gene (nrLSU), suggest that the two new species are distinct and monophyletic. S. subrugosoannulata is distinguished from other species of the genus Stropharia by the pileus covered with greyish-orange squamules in the centre, stipe light brown and surface covered with white triangular squamules. S. microaeruginosa differs from other species in its pileus bluish-grey when young becoming lighter towards margins, later greyish-turquoise lightens towards the edges and surface radially striate when young, lamellae adnate to subdecurrent, stipe with white squamules at the base, acanthocytes absent. The new record species from Jilin Province, Clitolyophyllum umbilicatum was also confirmed, based on morphological and molecular study. Here, we have given full descriptions of each species, colour images, illustrations and two phylogenetic trees that show the placement and relationship of the two new species and the new record are provided.

Abstract Traumatic dental injuries (TDIs) of teeth occur frequently in children and adolescents. TDIs that impact the periodontal tissues and alveolar tissue can be classified into concussion, subluxation, extrusive luxation, intrusive luxation, lateral luxation, and avulsion. In these TDIs, management of injured soft tissue, mainly periodontal ligament, and dental pulp, is crucial in maintaining the function and longevity of the injured teeth. Factors that need to be considered for management in laxation injuries include the maturation stage of the traumatic teeth, mobility, direction of displacement, distance of displacement, and whether there are alveolar fractures. In avulsion, the maturation stage of the permanent tooth, the out-socket time, storage media/condition of the avulsed tooth, and management of the PDL should also be considered. Especially, in this review, we have subdivided the immature tooth into the adolescent tooth (Nolla stage 9) and the very young tooth (Nolla stage 8 and below). This consensus paper aimed to discuss the impacts of those factors on the trauma management and prognosis of TDI to provide a streamlined guide for clinicians from clinical evaluation, diagnostic process, management plan decision, follow-up, and orthodontic treatment for tooth luxation and avulsion injuries.

Abstract As an important part of rotating machinery, gearboxes often fail due to their complex working conditions and harsh working environment. Therefore, it is very necessary to effectively extract the fault features of the gearboxes. Gearbox fault signals usually contain multiple characteristic components and are accompanied by strong noise interference. Traditional sparse modeling methods are based on synthesis models, and there are few studies on analysis and balance models. In this paper, a balance nonconvex regularized sparse decomposition method is proposed, which based on a balance model and an arctangent nonconvex penalty function. The sparse dictionary is constructed by using Tunable Q-Factor Wavelet Transform (TQWT) that satisfies the tight frame condition, which can achieve efficient and fast solution. It is optimized and solved by alternating direction method of multipliers (ADMM) algorithm, and the non-convex regularized sparse decomposition algorithm of synthetic and analytical models are given. Through simulation experiments, the determination methods of regularization parameters and balance parameters are given, and compared with the L1 norm regularization sparse decomposition method under the three models. Simulation analysis and engineering experimental signal analysis verify the effectiveness and superiority of the proposed method.

Abstract Background The interplay between metabolic disorders and chronic kidney disease (CKD) has been well-documented. However, the connection between CKD and atherogenic index of plasma (AIP) remains understudied. This research delves into the correlation between these two factors, aiming to shed new light on their potential association. Methods The relationship between AIP and CKD was evaluated using a weighted multivariate logistic regression model, and the curvilinear relationship between AIP and CKD was explored through smooth curve fitting. We engaged a recursive partitioning algorithm in conjunction with a two-stage linear regression model to precisely determine the inflection point. By conducting stratified analyses, the heterogeneity within subpopulations was explored. Results In the regression model that accounted for all covariates, ORs (95% CI) for the association between CKD and AIP were 1.12 (0.91, 1.36), indicating no significant association between AIP and CKD. However, sensitivity analyses suggested that the relationship between them may be non-linear. Smooth curve analysis confirmed the non-linear relationship between AIP and CKD, identifying an inflection point at -0.55. Below this threshold, AIP exhibited a significant inverse correlation with CKD. Conversely, above this threshold, a pronounced positive correlation was detected. Stratified analyses elucidated that a non-linear association between AIP and CKD was observed among female participants and those aged 50 and above. Conclusion We found a curvilinear relationship between chronic kidney disease and atherogenic index of plasma.

Abstract Background Pulpotomy is a crucial method to preserve primary teeth until natural exfoliation. This study aimed to evaluate the clinical and radiographic outcomes of pulpotomy with iRoot BP Plus in primary molars and to explore the association between hemostasis time and these outcomes. Methods Primary molars that underwent iRoot BP Plus pulpotomy and were followed for at least 12 months were selected for this study. Clinical and radiographic data were collected, and the success rate was analyzed in relation to factors such as hemostasis time, tooth type, and arch type. The tests of significance used were the chi-square test, Fisher’s exact test, or Kruskal-Wallis test. Statistical significance was set at P 0.05). Conclusions Pulpotomy using iRoot BP Plus in primary molars achieved favorable results. The hemostasis time may not significantly impact the outcomes of pulpotomy using iRoot BP Plus in primary molars.

Previous studies have acknowledged the impact of weather changes on retail uncertainty. They primarily focus on understanding how weather conditions affect offline consumer behavior and aim to develop effective marketing strategies. However, there is little research on the complex impact of weather on online shopping behavior. To bridge this gap, we conduct a study with a sample of 261 consumers from China with shopping experience in community retail shops (CRSs). We utilize the S-O-R model and theories, including meteorological emotional effect theory, emotional coherence, and meteorological psychology, to model and elucidate the relationship between weather and consumers’ online shopping behavior in CRS. Our findings reveal that weather conditions affect consumers’ spending patterns and purchase diversity, mediated by consumers’ emotions and risk aversion when they comfortably shop online at home. Furthermore, employing the fsQCA model, we identify the critical path through which weather conditions and consumer types influence risk-aversion awareness. The results provide management implications for retailers to develop online marketing strategies for different consumer types.

Abstract Drawing on narrative transportation theory, we propose that when people consume a cultural product, they consume their emotions and memories through collective storytelling. Such emotions and memories are amplified by user comments on social media, enhancing the product’s influence and triggering audience engagement. We collected public data from NetEase Cloud Music—a major music streaming platform in mainland China—to investigate how the emotions and memories expressed in user comments influence the songs’ impact. Findings indicate that autobiographical narratives and negative emotions in user comments significantly boost a song’s influence. Moreover, user comments are particularly effective in promoting emerging artists with limited resources compared to their more established counterparts. This study advances the narrative transportation theory by emphasizing the role of active audiences and collective storytelling. Empirically, it extends the existing literature on the factors influencing cultural products on music streaming platforms in a non-Western context.

Abstract Referring to the intestinal ischemic injury caused by sudden interruption of the blood supply, acute mesenteric ischemia (AMI) is a highly fatal emergency with mortality rates varying from 58 to 80%. The aim of this study was to explore the effect of temperature on AMI admission. This was a retrospective, multicentric study. The medical records of 1477 patients with verified AMI who were consecutively admitted to 3 hospitals anytime between January 2010 and December 2020 were included in the study. Distributed lag non-linear model was applied, the model was adjusted for temperature, atmospheric pressure, relative humidity, year, holiday, day of the week, time and seasonality. AMI exhibited obvious sex preference, AMI patients tended to be male (M/F ratio = 2.3:1) and in their late 50 s. Hospital admissions of acute mesenteric arterial thromboembolism (AMAT) increased significantly with high temperatures on day of exposure and lag 0–14 day. The effect curve of daily average temperature on acute mesenteric venous thromboembolism (AMVT) admission was J-shaped, and the duration of cold effect was longer, while the duration of heat effect was shorter. An increase in hospital admissions of AMVT was found above 20 °C at lag 0–30. For the first time, our study indicated that temperature is significantly associated with the risk of AMI. Although it is not possible to always avoid exposure to extreme temperatures, one should be aware of dramatic temperature fluctuations and take appropriate precautions.

Abstract Background Cervical cancer, encompassing squamous cell carcinoma and endocervical adenocarcinoma (CESC), presents a considerable risk to the well-being of women. Recent studies have reported that squalene epoxidase (SQLE) is overexpressed in several cancers, which contributes to cancer development. Methods RNA sequencing data for SQLE were obtained from The Cancer Genome Atlas. In vitro experiments, including colorimetry, colony formation, Transwell, RT-qPCR, and Western blotting were performed. Furthermore, a transplanted CESC nude mouse model was constructed to validate the tumorigenic activity of SQLE in vivo. Associations among the SQLE expression profiles, differentially expressed genes (DEGs), immune infiltration, and chemosensitivity were examined. The prognostic value of genetic changes and DNA methylation in SQLE were also assessed. Results SQLE mRNA expression was significantly increased in CESC. ROC analysis revealed the strong diagnostic ability of SQLE toward CESC. Patients with high SQLE expression experienced shorter overall survival. The promotional effects of SQLE on cancer cell proliferation, metastasis, cholesterol synthesis, and EMT were emphasized. DEGs functional enrichment analysis revealed the signaling pathways and biological processes. Notably, a connection existed between the SQLE expression and the presence of immune cells as well as the activation of immune checkpoints. Increased SQLE expressions exhibited increased chemotherapeutic responses. SQLE methylation status was significantly associated with CESC prognosis. Conclusion SQLE significantly affects CESC prognosis, malignant behavior, cholesterol synthesis, EMT, and immune infiltration; thereby offering diagnostic and indicator roles in CESC. Thus, SQLE can be a novel therapeutic target in CESC treatment.

Abstract Multiple synchronous lung cancers (MSLCs) constitute a unique subtype of lung cancer. To explore the genomic and immune heterogeneity across different pathological stages of MSLCs, we analyse 16 MSLCs from 8 patients using single-cell RNA-seq, single-cell TCR sequencing, and bulk whole-exome sequencing. Our investigation indicates clonally independent tumours with convergent evolution driven by shared driver mutations. However, tumours from the same individual exhibit few shared mutations, indicating independent origins. During the transition from pre-invasive to invasive adenocarcinoma, we observe a shift in T cell phenotypes characterized by increased Treg cells and exhausted CD8+ T cells, accompanied by diminished cytotoxicity. Additionally, invasive adenocarcinomas exhibit greater neoantigen abundance and a more diverse TCR repertoire, indicating heightened heterogeneity. In summary, despite having a common genetic background and environmental exposure, our study emphasizes the individuality of MSLCs at different stages, highlighting their unique genomic and immune characteristics.

Abstract Background Loss-of-function mutations of ZBTB24 cause immunodeficiency, centromeric instability, and facial anomalies syndrome 2 (ICF2). ICF2 is a rare autosomal recessive disorder with immunological defects in serum antibodies and circulating memory B cells, resulting in recurrent and sometimes fatal respiratory and gastrointestinal infections. The genotype–phenotype correlation in patients with ICF2 indicates an essential role of ZBTB24 in the terminal differentiation of B cells. Methods We used the clustered regularly interspaced short palindromic repeats (CRISPER)/Cas9 technology to generate B cell specific Zbtb24-deficient mice and verified the deletion specificity and efficiency by quantitative polymerase chain reaction (Q-PCR) and western blotting analyses in fluorescence-activated cell sorting (FACS)-sorted cells. The development, phenotype of B cells and in vivo responses to T cell dependent or independent antigens post immunization were analyzed by flow cytometry and enzyme-linked immunosorbent assay (ELISA). Adoptive transfer experiment in combination with in vitro cultures of FACS-purified B cells and RNA-Seq analysis were utilized to specifically determine the impact of Zbtb24 on B cell biology as well as the underlying mechanisms. Results Zbtb24 is dispensable for B cell development and maintenance in naive mice. Surprisingly, B cell specific deletion of Zbtb24 does not evidently compromise germinal center reactions and the resulting primary and secondary antibody responses induced by T cell dependent antigens (TD-Ags), but significantly inhibits T cell independent antigen-elicited antibody productions in vivo. At the cellular level, Zbtb24-deficiency specifically impedes the plasma cell differentiation of B1 cells without impairing their survival, activation and proliferation in vitro. Mechanistically, Zbtb24-ablation attenuates heme biosynthesis partially through mTORC1 in B1 cells, and addition of exogenous hemin abrogates the differentiation defects of Zbtb24-null B1 cells. Conclusions Zbtb24 seems to regulate antibody responses against TD-Ags B cell extrinsically, but it specifically promotes the plasma cell differentiation of B1 cells via heme synthesis in mice. Our study also suggests that defected B1 functions contribute to recurrent infections in patients with ICF2.

Abstract Extensive research has been conducted on visible-light and longer-wavelength infrared-light storage phosphors, which are utilized as promising rewritable memory media for optical information storage applications in dark environments. However, storage phosphors emitting in the deep ultraviolet spectral region (200–300 nm) are relatively lacking. Here, we report an appealing deep-trap ultraviolet storage phosphor, ScBO3:Bi3+, which exhibits an ultra-narrowband light emission centered at 299 nm with a full width at half maximum (FWHM) of 0.21 eV and excellent X-ray energy storage capabilities. When persistently stimulated by longer-wavelength white/NIR light or heated at elevated temperatures, ScBO3:Bi3+ phosphor exhibits intense and long-lasting ultraviolet luminescence due to the interplay between defect levels and external stimulus, while the natural decay in the dark at room temperature is extremely weak after X-ray irradiation. The impact of the spectral distribution and illuminance of ambient light and ambient temperature on ultraviolet light emission has been studied by comprehensive experimental and theoretical investigations, which elucidate that both O vacancy and Sc interstitial serve as deep electron traps for enhanced and prolonged ultraviolet luminescence upon continuous optical or thermal stimulation. Based on the unique spectral features and trap distribution in ScBO3:Bi3+ phosphor, controllable optical information read-out is demonstrated via external light or heat manipulation, highlighting the great potential of ScBO3:Bi3+ phosphor for advanced optical storage application in bright environments.

Abstract Background Visualization approaches transform high-dimensional data from single cell RNA sequencing (scRNA-seq) experiments into two-dimensional plots that are used for analysis of cell relationships, and as a means of reporting biological insights. Yet, many standard approaches generate visuals that suffer from overplotting, lack of quantitative information, and distort global and local properties of biological patterns relative to the original high-dimensional space. Results We present scBubbletree, a new, scalable method for visualization of scRNA-seq data. The method identifies clusters of cells of similar transcriptomes and visualizes such clusters as “bubbles” at the tips of dendrograms (bubble trees), corresponding to quantitative summaries of cluster properties and relationships. scBubbletree stacks bubble trees with further cluster-associated information in a visually easily accessible way, thus facilitating quantitative assessment and biological interpretation of scRNA-seq data. We demonstrate this with large scRNA-seq data sets, including one with over 1.2 million cells. Conclusions To facilitate coherent quantification and visualization of scRNA-seq data we developed the R-package scBubbletree, which is freely available as part of the Bioconductor repository at: https://bioconductor.org/packages/scBubbletree/

In this paper, we study the following Schrödinger equations with potentials and general nonlinearities \begin{equation*} \begin{cases} -\Delta u+V(x)u+\lambda u=|u|^{q-2}u+\beta f(u), \\ \int |u|^2dx=\Theta, \end{cases} \end{equation*} both on $\mathbb{R}^N$ as well as on domains $\Omega_r$ where $\Omega_r \subset \mathbb{R}^N$ is an open bounded convex domain and $r>0$ is large. The exponent satisfies $2+\frac{4}{N}\leq q\leq2^*=\frac{2 N}{N-2}$ and $f:\mathbb{R}\rightarrow \mathbb{R}$ satisfies $L^2$-subcritical or $L^2$-critical growth. This paper generalizes the conclusion of Bartsch et al. in [4]. Moreover, we consider the Sobolev critical case and $L^2$-critical case of the above problem.

Abstract Colorectal cancer (CRC) is a wide-spread gastrointestinal cancer that is associated with augmented morbidity and mortality, and we do not yet have a deep understanding of its epidemiology and carcinogenicity. The transcriptome can reveal the complexity and heterogeneity of tumors and uncover new biomarkers or treatment options. In this study, we identified messenger RNAs (mRNAs), long non-coding RNAs (lncRNAs), round RNAs (circRNAs), and microRNAs (miRNAs) using whole-transcriptome sequencing and generated competing endogenous RNA (ceRNA) modulatory axes. We conducted whole transcriptome sequencing on 10 CRC and para-cancer (CRCP) samples and discovered 2465 differentially expressed (DE) mRNAs (DEmRNAs), 77 DE miRNAs (DEmiRNAs). 2852 DE lncRNAs (DElncRNAs) and 1477 DE circRNAs (DEcircRNAs). In addition, utilizing co-DE analysis, we generated the ceRNA axis. Subsequently, we employed the ceRNA axis to identify essential genes and corresponding associations with lncRNAs, circRNAs, and miRNAs in CRC. ceRNA regulatory network including mRNA-miRNA-lncRNA and mRNA-miRNA-circRNA. These modulatory axes potentially modulate the positive regulation of smooth muscle contraction, melanosome, plasma membrane, integral plasma membrane component and so on. Finally, the results of RNA sequencing (RNA-SEQ) were combined with the TCGA and GEO databases, and the DEGs strongly correlated with the TCGA-COAD overall survival (OS) as estimated by univariate cox and logarithmic rank analyses were cross-analyzed, and the co-upregulated DEGs were screened. Among the many DEs, KPNA2 was chosen for additional analysis. Using invitro experimentations, western blot, CCK8, EdU and other experiments were performed to verify the results. We found siRNA-based KPNA2 depletion reduces bladder cancer cells’ viability, migratory, and proliferative activities, which showed that the DEmRNA profiles were comparable to the sequencing information, confirming that the sequencing data were very reliable. These evidences highlight the ceRNA regulatory mechanisms in CRC and will aid future research into the molecular mechanisms behind colorectal cancer prevention and treatment.

Abstract Blinatumomab has emerged as a promising component of first-line therapy for acute B-cell precursor lymphoblastic leukemia (BCP-ALL), bolstering treatment efficacy. To mitigate CD19 selection pressure and reduce the incidence of blinatumomab-associated toxicities, pre-treatment chemotherapy is recommended before administering blinatumomab. From September 2022 to December 2023, we conducted a single-arm, multicenter, phase 2 trial (NCT05557110) in newly diagnosed Philadelphia chromosome-negative BCP-ALL (Ph-negative BCP-ALL) patients. Participants received induction treatment with reduced-dose chemotherapy (RDC), comprising idarubicin, vindesine, and dexamethasone over 7 days, followed by 2 weeks of blinatumomab. Those failing to achieve composite complete remission (CRc) received an additional 2 weeks of blinatumomab. The primary endpoint was the CRc rate post initial induction treatment. Of the 35 enrolled patients, 33 (94%) achieved CRc after 2 weeks of blinatumomab, with 30 (86%) achieving measurable residual disease (MRD) negativity. Two patients extended blinatumomab to 4 weeks. With either 2 or 4 weeks of blinatumomab treatment, all patients achieved CR (35/35) and 89% (31/35) were MRD negativity. The median time to CR was 22 days. Immune effector cell-associated neurotoxicity syndrome was limited (14%, all grade 1). Non-hematological adverse events of grade 3 or higher included pneumonia (17%), sepsis (6%), and cytokine release syndrome (9%). With a median follow-up of 11.5 months, estimated 1-year overall survival and 1-year progression-free survival rates were 97.1% and 82.2%, respectively. These findings affirm that RDC followed by blinatumomab is an effective and well-tolerated induction regimen for newly diagnosed Ph-negative BCP-ALL, supporting a shift towards less intensive and more targeted therapeutic approaches. Trial registration: https://www.clinicaltrials.Gov . Identifier NCT05557110.

Background: The homologous recombination deficiency (HRD) score serves as a promising biomarker to identify patients who are eligible for treatment with PARP inhibitors (PARPi). Previous studies have suggested a 3-biomarker Genomic Instability Score (GIS) threshold of ≥ 42 as a valid biomarker to predict response to PARPi in patients with ovarian cancer and breast cancer. However, the GIS threshold for prostate cancer (PCa) is still lacking. Here, we conducted an exploratory analysis to investigate an appropriate HRD score threshold and to evaluate its ability to predict response to PARPi in PCa patients. Methods: A total of 181 patients with metastatic castration-resistant PCa were included in this study. Tumor tissue specimens were collected for targeted next-generation sequencing for homologous recombination repair (HRR) genes and copy number variation (CNV) analysis. The HRD score was calculated based on over 50,000 single-nucleotide polymorphisms (SNP) distributed across the human genome, incorporating three SNP-based assays: loss of heterozygosity, telomeric allelic imbalance, and large-scale state transition. The HRD score threshold was set at the last 5th percentile of the HRD scores in our cohort of known HRR-deficient tumors. The relationship between the HRD score and the efficacy in 16 patients of our cohort who received PARPi treatment were retrospectively analyzed. Results: Genomic testing was succeeded in 162 patients. In our cohort, 61 patients (37.7%) had HRR mutations (HRRm). BRCA mutations occurred in 15 patients (9.3%). The median HRD score was 4 (ranged from 0 to 57) in the total cohort, which is much lower than that in breast and ovarian cancers. Patients who harbored HRRm and BRCA or TP53 mutations had higher HRD scores. CNV occured more frequently in patients with HRRm. The last 5th percentile of HRD scores was 43 in the HRR-mutant cohort and consequently HRD high was defined as HRD scores ≥43. In the 16 patients who received PARPi in our cohort, 4 patients with a high HRD score achieved an objective response rate (ORR) of 100% while 12 patients with a low HRD score achieved an ORR of 8.3%. Progression-free survival (PFS) in HRD high patients was longer compared to HRD low patients, regardless of HRRm. Conclusions: A HRD score threshold of 43 was established and preliminarily validated to predict the efficacy of PARPi in this study. Future studies are needed to further verify this threshold.

Introducing additional oxidizers in aluminized explosives is an effective way to improve energy performance by enhancing the secondary combustion reaction. In this work, perfluorocarbon as oxidizer has been introduced into TATB/Al based energetic materials to improve combustion reaction and energy output performance. The uniform TATB/Al/perfluorocarbon composites are prepared through acoustic resonance mixed technology, and the energy and pressure output performance are fully studied in air blast and underwater explosion. A significantly exothermic peak derived from the reaction between fluorine and Al is observed between 540 ℃ and 580 ℃ for TATB/Al/perfluorocarbon. The heat of explosion of TATB/Al/perfluorocarbon is increased first and then decreased with F/Al ratio from 0 to 0.608. The highest heat of explosion is 6021 J/g for TATB/Al/perfluorocarbon with F/Al ratio of 0.274. Furthermore, the enhanced working capacity, the significantly enlarged fireball and relatively high overpressure are obtained for TATB/Al/perfluorocarbon. More importantly, the shock impulse and first bubble oscillation time of TATB/Al/perfluorocarbon have been increased by 23.2% and 21.18% during underwater explosion, respectively. The results further illustrate that adding perfluorocarbon is a feasible approach to enhance energy output due to combustion reaction between fluorine and Al, which can be applied in explosives and propellants.

The undercooled solidification of the Inconel 718 superalloy under high magnetic field was performed for the first time at high undercoolings (∼ 200 °C). The results show that the high magnetic field can significantly refine the grains of the undercooled alloys, with the average grain size decreasing from 241 ± 92 μm at 0 T to about a third under high magnetic fields (3 T ∼ 9 T). Detailed EBSD analysis provides clear evidence that Icosahedral Short-Range Order (ISRO) enhanced nucleation occurs. The present work opens up a new way for grain refinement of alloys.

This study examines the understanding of a linguistically responsive teaching framework (LRT) among pre-service teachers (PSTs). This study employed a mixed-method approach. The quantitative data did not demonstrate statistically significant differences between bi-/multilingual and monolingual PSTs in their responses to the LRT framework. However, qualitative analysis revealed variations in how bi-/multilingual and monolingual PSTs perceived the role of language and power access. Emergent findings indicated that White male PSTs may exhibit resistance to understanding or meeting the needs of ELs. Teacher preparation programs may offer immersive learning experiences in different languages, especially for those who may lack such exposure.

Parkinson's disease (PD) is a neurodegenerative condition marked by a steady loss of dopaminergic neurons in the brain's substantia nigra. Prompt identification and tracking of PD progression are essential for prompt intervention and efficient PD care. In this study, we developed an immunofluorescence detection approach for α-synuclein (α-syn), a critical biomarker associated with PD, that is both extremely sensitive and specific. Using polyethylene glycol (PEG)-functionalized magnetic beads (MBs) and an Ag+ fluorescence probe (Ag+-FP) based on Rhodamine 6 G, the suggested method makes use of an immunofluorescence detection system. The system's workings are based on antigen-antibody complexes. Identified as Ab1-MBs@α-syn@Ab2-Ag NPs, the immuno-complexes encapsulate α-synuclein between anti-α-synuclein antibodies (Ab1) fixed on amino-MBs and Ag Nanoparticles functionalized with matching Ab2. α-synuclein detection was accomplished at a limit of less than 8 pg/mL through optimization of pH, reaction duration, and antibody concentration. The method showed very little cross-reactivity with other widely used biomarkers and a high specificity. The system showed a linear range of 524.8 ng/mL to 0.2 ng/mL. The results, which showed recovery values ranging from 97.00 % to 99.57 % and were consistent with those obtained using a commercial ELISA kit, indicated the system's potential for clinical applications in the diagnosis and monitoring of PD.

Accelerating green innovation is crucial for achieving high-quality development in China. Despite this importance, empirical evidence on the harmonization techniques in the context of carbon-trading policies has been remarkably thin. To address this gap, we employed the difference-in-difference (DID) and spatial difference-in-difference (S-DID) models using panel data from 2007 to 2017 for 30 Chinese provinces. Our findings reveal that the carbon-trading policy contributes significantly to the coordinated advancement of green technologies across Chinese provinces and exhibits a local siphoning effect. Specifically, the pilot areas of the policy have attracted talent from neighboring regions, which has fostered local cooperation and promoted coordinated innovation in green technologies within the region.

Microscale energetic materials have garnered considerable attention because they can be integrated in microelectromechanical systems for several potential applications. Hexanitrostilbene (HNS) has been widely utilized in ignition and initiation devices owing to its excellent thermal and shock stability and high sensitivity to short pulse shock waves. To meet the energy release requirements of micro-detonation devices, HNS sticks were prepared using direct ink writing and their reaction and flame propagation properties were studied. HNS particles sized 17.5 µm to 5 µm and ∼500 nm was prepared. Then, the viscosity of HNS-based inks prepared via acoustic resonance technology decreased when the particle size decreased or when the HNS content reduced from 97 wt.%, 95 wt.%, and 92 wt.%, to 90 wt.%. Additionally, the HNS-based inks with different binders exhibited different viscosity. The effect of the inner diameter of needle (0.4 mm, 0.6 mm, and 0.9 mm), printing rate (13 mm/s, 15 mm/s, 17 mm/s, 19 mm/s), and pressure (0.05 MPa, 0.1 MPa, 0.15 MPa, 0.2 MPa) on the width of HNS sticks was also elucidated. HNS-based sticks with a diameter of 0.9 mm underwent self-sustaining combustion reactions, and the burning rate increased from 5.1 mm/s to 6.8 mm/s as the particle size decreased from 17.5 µm to 500 nm. Overall, this work provides an effective approach to prepare microscale HNS for integration into micro-energetic devices.

AbstractAlthough MXene sheets are highly conductive, it is still challenging to prepare MXene complex functional materials for flexible electronics by simple and effective methods. In 3D printing, especially direct ink writing (DIW), different materials are used to create complex 3D shapes by formulating inks with controlled rheological properties. Herein, a printable MXene ink is developed, exhibiting good rheological properties, to print different complex shapes, and potentially manufacture electronic devices such as sensors. Then, we fabricated a highly sensitive hierarchical structure MXene composite materials composed of two layers of bionic micro-spine microstructure and network structure, formed by 3D printing and freeze casting. The obtained MXene composite materials exhibit good pressuring sensing properties with a sensitivity of 17.5 kPa−1, a fast response time (