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Abstract Cross-linked polymers with covalent adaptable networks (CANs) can be reprocessed under external stimuli owing to the exchangeability of dynamic covalent bonds. Optimization of reprocessing conditions is critical since increasing the reprocessing temperature costs more energy and even deteriorates the materials, while reducing the reprocessing temperature via molecular design usually narrows the service temperature range. Exploiting CO2 gas as an external trigger for lowering the reprocessing barrier shows great promise in low sample contamination and environmental friendliness. Herein, we develop a type of CANs incorporated with ionic clusters that achieve CO2-facilitated recyclability without sacrificing performance. The presence of CO2 can facilitate the rearrangement of ionic clusters, thus promoting the exchange of dynamic bonds. The effective stress relaxation and network rearrangement enable the system with rapid recycling under CO2 while retaining excellent mechanical performance in working conditions. This work opens avenues to design recyclable polymer materials with tunable dynamics and responsive recyclability.

Abstract Background Type 2 diabetes mellitus (T2D) is associated with an increased risk of cognitive dysfunction. Angiopoietin-like protein 8 (ANGPTL8) is an important regulator in T2D, but the role of ANGPTL8 in diabetes-associated cognitive dysfunction remains unknown. Here, we explored the role of ANGPTL8 in diabetes-associated cognitive dysfunction through its interaction with paired immunoglobulin-like receptor B (PirB) in the central nervous system. Methods The levels of ANGPTL8 in type 2 diabetic patients with cognitive dysfunction and control individuals were measured. Mouse models of diabetes-associated cognitive dysfunction were constructed to investigate the role of ANGPTL8 in cognitive function. The cognitive function of the mice was assessed by the Barnes Maze test and the novel object recognition test, and levels of ANGPTL8, synaptic and axonal markers, and pro-inflammatory cytokines were measured. Primary neurons and microglia were treated with recombinant ANGPTL8 protein (rA8), and subsequent changes were examined. In addition, the changes induced by ANGPTL8 were validated after blocking PirB and its downstream pathways. Finally, mice with central nervous system-specific knockout of Angptl8 and PirB −/− mice were generated, and relevant in vivo experiments were performed. Results Here, we demonstrated that in the diabetic brain, ANGPTL8 was secreted by neurons into the hippocampus, resulting in neuroinflammation and impairment of synaptic plasticity. Moreover, neuron-specific Angptl8 knockout prevented diabetes-associated cognitive dysfunction and neuroinflammation. Mechanistically, ANGPTL8 acted in parallel to neurons and microglia via its receptor PirB, manifesting as downregulation of synaptic and axonal markers in neurons and upregulation of proinflammatory cytokine expression in microglia. In vivo, PirB −/− mice exhibited resistance to ANGPTL8-induced neuroinflammation and synaptic damage. Conclusion Taken together, our findings reveal the role of ANGPTL8 in the pathogenesis of diabetes-associated cognitive dysfunction and identify the ANGPTL8-PirB signaling pathway as a potential target for the management of this condition.

Abstract Background Selenium nanoparticles (SeNPs) are increasingly gaining attention due to its characteristics of low toxicity, high activity, and stability. Additionally, Bacillus licheniformis, as a probiotic, has achieved remarkable research outcomes in diverse fields such as medicine, feed processing, and pesticides, attracting widespread attention. Consequently, evaluating the activity of probiotics and SeNPs is paramount. The utilization of probiotics to synthesize SeNPs, achieving large-scale industrialization, is a current hotspot in the field of SeNPs synthesis and is currently the most promising synthetic method. To minimize production costs and maximize yield of SeNPs, this study selected agricultural by-products that are nutrient-rich, cost-effective, and readily available as culture medium components. This approach not only fulfills industrial production requirements but also mitigates the impact on downstream processes. Results The experimental findings revealed that SeNPs synthesized by B. licheniformis F1 exhibited a spherical morphology with diameters ranging from 110 to 170 nm and demonstrating high stability. Both the secondary metabolites of B. licheniformis F1 and the synthesized SeNPs possessed significant free radical scavenging ability. To provide a more robust foundation for acquiring large quantities of SeNPs via fermentation with B. licheniformis F1, key factors were identified through single-factor experiments and response surface methodology (RSM) include a 2% seed liquid inoculum, a temperature of 37 ℃, and agitation at 180 rpm. Additionally, critical factors during the optimization process were corn powder (11.18 g/L), soybean meal (10.34 g/L), and NaCl (10.68 g/L). Upon validating the optimized conditions and culture medium, B. licheniformis F1 can synthesize nearly 100.00% SeNPs from 5 mmol/L sodium selenite. Subsequently, pilot-scale verification in a 5 L fermentor using the optimized medium resulted in a shortened fermentation time, significantly reducing production costs. Conclusion In this study, the efficient production of SeNPs by the probiotic B. licheniformis F1 was successfully achieved, leading to a significant reduction in fermentation costs. The exploration of the practical applications of this strain holds significant potential and provides valuable guidance for facilitating the industrial-scale implementation of microbial synthesis of SeNPs.

Abstract Analogous of pixels to two-dimensional pictures, voxels—in the form of either small cubes or spheres—are the basic building blocks of three-dimensional objects. However, precise manipulation of viscoelastic bio-ink voxels in three-dimensional space represents a grand challenge in both soft matter science and biomanufacturing. Here, we present a voxelated bioprinting technology that enables the digital assembly of interpenetrating double-network hydrogel droplets made of polyacrylamide/alginate-based or hyaluronic acid/alginate-based polymers. The hydrogels are crosslinked via additive-free and biofriendly click reaction between a pair of stoichiometrically matched polymers carrying norbornene and tetrazine groups, respectively. We develop theoretical frameworks to describe the crosslinking kinetics and stiffness of the hydrogels, and construct a diagram-of-state to delineate their mechanical properties. Multi-channel print nozzles are developed to allow on-demand mixing of highly viscoelastic bio-inks without significantly impairing cell viability. Further, we showcase the distinctive capability of voxelated bioprinting by creating highly complex three-dimensional structures such as a hollow sphere composed of interconnected yet distinguishable hydrogel particles. Finally, we validate the cytocompatibility and in vivo stability of the printed double-network scaffolds through cell encapsulation and animal transplantation.

Abstract Background This paper attempted to clarify the role and mechanism of vacuolar protein sorting-associated protein 72 homolog (VPS72) in the progression of prostate cancer (PCa). Methods Clinical information and gene expression profiles of patients with prostate cancer were obtained from The Cancer Genome Atlas (TCGA). VPS72 expression in PCa and the potential mechanism by which VPS72 affects PCa progression was investigated. Next, we performed COX regression analysis to identify the independent prognostic factors of PCa, and constructed a nomogram. The sensitivity of chemotherapeutic medications was anticipated using “pRRophetic”. Subsequently, in vitro assays to validate the effect of VPS72 on PCa cell proliferation, migration and susceptibility to anti-androgen therapy. Results The expression of VPS72 was considerably higher in PCa tissues compared to normal tissues. Significant correlations were found between high VPS72 expression and a poor prognosis and adverse clinicopathological factors. The nomogram model constructed based on VPS72 expression has good predictive performance. According to GSEA, VPS72-related genes were enriched in the NF-kB pathways, cytokine-cytokine receptor interaction and chemokine signaling pathway in PCa. Although PCa with low VPS72 expression was more adaptable to chemotherapeutic medications, our in vitro experiment showed that VPS72 knockdown significantly decreased the PCa cell migration, proliferation, and resistance to anti-androgen therapy. Conclusions In summary our findings suggests that VPS72 could play a crucial role in the malignant progression of PCa, and its expression level can be employed as a possible biomarker of PCa prognosis.

Abstract Background Broussonetia papyrifera is an economically significant tree with high utilization value, yet its cultivation is often constrained by soil contamination with heavy metals (HMs). Effective scientific cultivation management, which enhances the yield and quality of B. papyrifera, necessitates an understanding of its regulatory mechanisms in response to HM stress. Results Twelve Metallothionein (MT) genes were identified in B. papyrifera. Their open reading frames ranged from 186 to 372 bp, encoding proteins of 61 to 123 amino acids with molecular weights between 15,473.77 and 29,546.96 Da, and theoretical isoelectric points from 5.24 to 5.32. Phylogenetic analysis classified these BpMTs into three subclasses: MT1, MT2, and MT3, with MT2 containing seven members and MT3 only one. The expression of most BpMT genes was inducible by Cd, Mn, Cu, Zn, and abscisic acid (ABA) treatments, particularly BpMT2e, BpMT2d, BpMT2c, and BpMT1c, which showed significant responses and warrant further study. Yeast cells expressing these BpMT genes exhibited enhanced tolerance to Cd, Mn, Cu, and Zn stresses compared to control cells. Yeasts harboring BpMT1c, BpMT2e, and BpMT2d demonstrated higher accumulation of Cd, Cu, Mn, and Zn, suggesting a chelation and binding capacity of BpMTs towards HMs. Site-directed mutagenesis of cysteine (Cys) residues indicated that mutations in the C domain of type 1 BpMT led to increased sensitivity to HMs and reduced HM accumulation in yeast cells; While in type 2 BpMTs, the contribution of N and C domain to HMs’ chelation possibly corelated to the quantity of Cys residues. Conclusion The BpMT genes are crucial in responding to diverse HM stresses and are involved in ABA signaling. The Cys-rich domains of BpMTs are pivotal for HM tolerance and chelation. This study offers new insights into the structure-function relationships and metal-binding capabilities of type-1 and − 2 plant MTs, enhancing our understanding of their roles in plant adaptation to HM stresses.

Abstract Background Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage destruction and inflammation. CC chemokine receptor 1 (CCR1), a member of the chemokine family and its receptor family, plays a role in the autoimmune response. The impact of BX471, a specific small molecule inhibitor of CCR1, on CCR1 expression in cartilage and its effects on OA remain underexplored. Methods This study used immunohistochemistry (IHC) to assess CCR1 expression in IL-1β-induced mouse chondrocytes and a medial meniscus mouse model of destabilization of the medial meniscus (DMM). Chondrocytes treated with varying concentrations of BX471 for 24 h were subjected to IL-1β (10 ng/ml) treatment. The levels of the aging-related genes P16INK4a and P21CIP1 were analyzed via western blotting, and senescence-associated β-galactosidase (SA-β-gal) activity was measured. The expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), aggrecan (AGG), and the transcription factor SOX9 were determined through western blotting and RT‒qPCR. Collagen II, matrix metalloproteinase 13 (MMP13), and peroxisome proliferator-activated receptor (PPAR)-γ expression was analyzed via western blot, RT‒qPCR, and immunofluorescence. The impact of BX471 on inflammatory metabolism-related proteins under PPAR-γ inhibition conditions (using GW-9662) was examined through western blotting. The expression of MAPK signaling pathway-related molecules was assessed through western blotting. In vivo, various concentrations of BX471 or an equivalent medium were injected into DMM model joints. Cartilage destruction was evaluated through Safranin O/Fast green and hematoxylin–eosin (H&E) staining. Results This study revealed that inhibiting CCR1 mitigates IL-1β-induced aging, downregulates the expression of iNOS, COX-2, and MMP13, and alleviates the IL-1β-induced decrease in anabolic indices. Mechanistically, the MAPK signaling pathway and PPAR-γ may be involved in inhibiting the protective effect of CCR1 on chondrocytes. In vivo, BX471 protected cartilage in a DMM model. Conclusion This study demonstrated the expression of CCR1 in chondrocytes. Inhibiting CCR1 reduced the inflammatory response, alleviated cartilage aging, and retarded degeneration through the MAPK signaling pathway and PPAR-γ, suggesting its potential therapeutic value for OA. Graphical Abstract

Objective: This study aimed to investigate the impact of different imaging parameters on stent imaging and stenosis assessment in a fast heart rate model. The goal was to reduce the radiation dose while ensuring image quality, and to provide a theoretical basis for optimizing computed tomography (CT) imaging parameters for stent imaging in patients with fast heart rates in future clinical practice. Methods: Different imaging parameters were set to obtain multiple sets of CT images of stents in a fast heart rate model. Four coronary artery stents with different internal diameters were used. Each stent was set to four levels of stenosis. Two different concentrations of iodine contrast agents were injected in batches. The Canon 320 CT scanner was used to perform scans at 100 kV and 120 kV tube voltages, and image reconstruction was performed using the stent reconstruction mode. Two radiologists, with more than three years of experience in coronary CT diagnosis, used a 5-point scoring method to subjectively evaluate image quality based on stent visualization, image quality, and stenosis assessment. Multiple regression analysis was conducted to assess the influence of stent diameter, stenosis level, tube voltage, and iodine contrast agent concentration on the subjective image quality scores. Results: The structures of the four stents could be visualized in all parameter combinations, but there were significant differences in the intraluminal display. The stent diameter, stenosis level, and iodine contrast agent concentration had a significant impact on the subjective image quality scores. The scores increased as the stent diameter increased and the stenosis level and iodine contrast agent concentration decreased. Moreover, the stent diameter had the strongest impact on the scores. Tube voltage did not significantly affect the subjective image quality scores. Conclusion: In fast heart rate conditions, the stent diameter, stenosis level, and iodine contrast agent concentration directly affect the image quality of stent CT imaging. Conversely, tube voltage had no impact on image quality. Our findings provided a theoretical basis for optimizing stent imaging protocols in patients with fast heart rates.

Abstract The relationship between humans and land environment within historical settlements reflects the intricate interplay between human societies, their construction activities, and the specific geographical contexts. Inadequate research into this relationship hinders a comprehensive understanding of the social spatial intricacies inherent in historical settlements. This paper adopts the theoretical framework of complex adaptive system and takes Shawan Ancient Town in Guangfu area of China as an example. Under the geographical background of sustainable land growth in the coastal zone, this study analyzed the subtle changes in the relationship between people and land during the historical construction, and the key findings of the investigation are threefold: (1) Land resources play a central role in the construction of human-land relationships in historical settlements. The geographical environment and social institutions serve as configuring factors in the formation and evolution of human-land relationships. These factors collectively determine the formation and evolution of human-land relationships. (2) Social space emerges as a pivotal manifestation of the human–environment relationship in historical settlements, transcending mere physical dimensions. Consequently, a holistic study of this relationship necessitates a comprehensive exploration not only of spatial configurations but also of the intricate interconnections among social bonds, structural formations, societal order, and settlement spatiality. (3) Drawing on the framework of complex adaptive systems theory, the study disentangles intricate elements within the human-land relationship of historical settlements. It distills and examines the manifestations of four intricate adaptive capacities—namely aggregation, non-linearity, flow, and diversity—alongside the mechanisms of tags, internal models, and fundamental building blocks. It is believed that the study of historical settlements in coastal areas needs to grasp the invariable social-spatial objects such as geographical environment, land form, local beliefs. Take it as a clue to sort out how other elements of change have iterated and transformed in the process of historical evolution, such as the rise and fall of families, land ownership changes and social class evolution. This paper explores the value connotation of historical settlements from the perspective of dialectic thinking of change and invariance with CAS theory, which has theoretical significance for protection of settlement's human-land relationship from the perspective of "social-spatial".

Abstract Background The La-related proteins (LARPs) are a superfamily of RNA-binding proteins associated with regulation of gene expression. Evidence points to an important role for post-transcriptional control of gene expression in germinating pollen tubes, which could be aided by RNA-binding proteins. Results In this study, a genome-wide investigation of the LARP proteins in eight plant species was performed. The LARP proteins were classified into three families based on a phylogenetic analysis. The gene structure, conserved motifs, cis-acting elements in the promoter, and gene expression profiles were investigated to provide a comprehensive overview of the evolutionary history and potential functions of ZmLARP genes in maize. Moreover, ZmLARP6c1 was specifically expressed in pollen and ZmLARP6c1 was localized to the nucleus and cytoplasm in maize protoplasts. Overexpression of ZmLARP6c1 enhanced the percentage pollen germination compared with that of wild-type pollen. In addition, transcriptome profiling analysis revealed that differentially expressed genes included PABP homologous genes and genes involved in jasmonic acid and abscisic acid biosynthesis, metabolism, signaling pathways and response in a Zmlarp6c1::Ds mutant and ZmLARP6c1-overexpression line compared with the corresponding wild type. Conclusions The findings provide a basis for further evolutionary and functional analyses, and provide insight into the critical regulatory function of ZmLARP6c1 in maize pollen germination.

In order to improve the efficiency of scientific research and innovation, China is accelerating the exploration and implementation of the “Open Bidding for Selecting the Best Candidates” mechanism. How to identify and select the high-level research teams and project leaders who are capable to make breakthroughs in core technologies is the key challenge of this new type of talents selection mechanism. Recent practical experience has shown that most of the research project leaders selected by this mechanism have one or more titles of talents. This paper aims at exploring whether the title of talents can fully reflect the research ability and team leadership of the scholars and then become necessary for selecting the best candidates. Based on a sample of selected project leaders, the empirical results show that although the title of talents facilitates the scholars to win honor and awards, the title of talents has no significant effects on their research achievements in terms of the quantity of academic papers, books, and projects, and also it is not related to their research leadership. Our findings provide policy implications that the title of talents should play a limited role in the “Open Bidding for Selecting the Best Candidates” mechanism.

Abstract Objective To develop a deep learning (DL) model for segmenting fat metaplasia (FM) on sacroiliac joint (SIJ) MRI and further develop a DL model for classifying axial spondyloarthritis (axSpA) and non-axSpA. Materials and methods This study retrospectively collected 706 patients with FM who underwent SIJ MRI from center 1 (462 axSpA and 186 non-axSpA) and center 2 (37 axSpA and 21 non-axSpA). Patients from center 1 were divided into the training, validation, and internal test sets (n = 455, 64, and 129). Patients from center 2 were used as the external test set. We developed a UNet-based model to segment FM. Based on segmentation results, a classification model was built to distinguish axSpA and non-axSpA. Dice Similarity Coefficients (DSC) and area under the curve (AUC) were used for model evaluation. Radiologists’ performance without and with model assistance was compared to assess the clinical utility of the models. Results Our segmentation model achieved satisfactory DSC of 81.86% ± 1.55% and 85.44% ± 6.09% on the internal cross-validation and external test sets. The classification model yielded AUCs of 0.876 (95% CI: 0.811–0.942) and 0.799 (95% CI: 0.696–0.902) on the internal and external test sets, respectively. With model assistance, segmentation performance was improved for the radiological resident (DSC, 75.70% vs. 82.87%, p 0.05). Conclusions DL is a novel method for automatic and accurate segmentation of FM on SIJ MRI and can effectively increase radiologist’s performance, which might assist in improving diagnosis and progression of axSpA. Critical relevance statement DL models allowed automatic and accurate segmentation of FM on sacroiliac joint MRI, which might facilitate quantitative analysis of FM and have the potential to improve diagnosis and prognosis of axSpA. Key points • Deep learning was used for automatic segmentation of fat metaplasia on MRI. • UNet-based models achieved automatic and accurate segmentation of fat metaplasia. • Automatic segmentation facilitates quantitative analysis of fat metaplasia to improve diagnosis and prognosis of axial spondyloarthritis. Graphical Abstract

Abstract Purpose A prevalent condition with a high probability of recurrence, non-muscle invasive bladder cancer (NMIBC) necessitates lifetime surveillance. In patients with pathologically confirmed NMIBC, our goal was to create a unique nomogram to predict recurrence after transurethral resection of bladder tumor (TURBT). Methods Our institution’s 91 NMIBC patients with complete follow-up data between January 2017 and February 2021 were included in the retrospective analysis. The nomogram predicting the 0.5, 1, 2 and 3-year likelihood of recurrence was created using multivariate Cox proportional hazard models to find the significant determinants of recurrence. Using the concordance index (C-index), calibration curves, receiver operating characteristic (ROC) curves, and decision curve analyses (DCA), we internally validated the nomogram. Results The significant factors related to NMIBC recurrence were age, blood platelet count, especially for the urine leukocyte count and mucus filament. The constructed nomogram performed well in the customized prediction of NMIBC recurrence at 6th, 12th, 24th and 36th month, of which the C-index was 0.724. The calibration curve and the ROC curve both validated the prediction accuracy. On DCA, the nomogram presented good net benefit gains across a wide range of threshold probabilities. Furthermore, the Nomogram-related risk score was used to divide the patient population into two groups with significant recurrence disparities. Conclusion For the prediction of NMIBC recurrence, our unique nomogram demonstrated a respectable degree of discriminative capacity, sufficient calibration, and considerable net benefit gain. There will be a need for additional internal and external validation.

Abstract Purpose The pathways underpinning suicide ideation (SI) and certain physical and psychological factors in patients with advanced breast cancer remain unclear. This study develops and validates a mediation model that delineates the associations between several multidimensional variables and SI in Chinese patients with advanced breast cancer. Methods Patients with advanced breast cancer (n = 509) were recruited as study participants from 10 regional cancer centers across China from August 2019 to December 2020. Participants were required to complete five questionnaires using an electronic patient-reported outcomes (ePRO) system: 9 item- Patient Health Questionnaire (PHQ-9), Hospital Anxiety and Depression Scale (HADS), Insomnia Severity Index (ISI), 5-level EQ-5D (EQ-5D-5L), and MD Anderson Symptom Inventory (MDASI). Risk factors for SI were identified using multivariable logistic regression, and inputted into serial multiple mediation models to elucidate the pathways linking the risk factors to SI. Results SI prevalence was 22.8% (116/509). After adjusting for covariates, depression (odds ratio [OR] = 1.384), emotional distress (OR = 1.107), upset (OR = 0.842), and forgetfulness (OR = 1.236) were identified as significant independent risk factors (all p

Abstract This study aimed to assess haematopoietic stem cell transplantation (HSCT) safety and efficacy while exploring strategies for optimising outcomes in patients with hepatitis-associated aplastic anaemia (HAAA). We retrospectively reviewed 35 HAAA patients who underwent HSCT at a large Chinese blood disease hospital between 2008 and 2022. HAAA patients receiving HSCT typically presented with severe (28.6%) and very severe (65.7%) AA. Male patients predominated (68.6%), with a median onset age of 23 years (range, 9–44). Haploidentical donor-HSCT and matched sibling donor-HSCT were in comparable proportions. The 5-year overall survival (OS) rate was 74.0%, with cumulative incidences of grade II–IV acute and chronic graft-versus-host disease (GVHD) at 37.1% and 22.4%, respectively. A diagnosis-to-HSCT interval ≥ 75 days, acute GVHD, and post-HSCT liver events (e.g., hepatic GVHD and a three-fold increase in aminotransferase or bilirubin) significantly worsened 5-year OS. In the multivariate models, recipients with sex-matched grafts had better OS, and those with younger male donors had a lower incidence of II–IV aGVHD. Higher HLA matching degree (HLA > = 7/10) was an independent prognostic factor associated with better OS and GFFS. A diagnosis-to-HSCT interval ≥ 75 days was predictive of post-transplant liver events in HAAA patients. In conclusion, HSCT was a safe and effective treatment for HAAA. Early transplantation, careful donor selection and improving post-transplant liver events were crucial to optimise outcomes.

IntroductionProstate cancer (PCa), one of the most prevalent malignant tumors in the genitourinary system, is characterized by distant metastasis and the development of castration-resistant prostate cancer (CRPC), which are major determinants of poor prognosis. Current treatment approaches for PCa primarily involve surgery and endocrine therapy, but effective strategies for managing distant metastasis and CRPC remain limited.MethodsWe utilized qPCR, WB, and other methods to measure the expression levels of respective proteins, concurrently assessing lipid metabolism to validate the role of FATP5 in lipid metabolism. Additionally, we employed bioinformatics analysis and WB techniques to explore the corresponding mechanisms.ResultsIn this study, we conducted an analysis of clinical samples and public databases to identify differential expression of FATP5 and further investigated its association with clinical outcomes. Through biochemical and functional experiments, we elucidated the potential underlying mechanisms by which FATP5 facilitates the progression of PCa. Our findings demonstrate that specific upregulation of FATP5 significantly enhances proliferation, migration, and invasion of PCa cell lines, while also modulating lipid metabolism in PCa. Mechanistically, the expression of FATP5 is closely associated with the Hippo signaling pathway, as it promotes the nuclear accumulation of YAP1 by inhibiting AMPK and facilitating the activation of β-catenin and RHOA. Furthermore, the transcription of FATP5 is mediated by TEAD4, and this transcriptional activation requires the involvement of YAP1.DiscussionFATP5 is highly expressed in prostate cancer and can enhance the biological activity and lipid metabolism of prostate cancer. We have also elucidated that FATP5 is regulated by the Hippo signaling pathway. This provides a new potential target for the treatment of prostate cancer.

The optimal treatment for patients with severe aplastic anemia (SAA) who fail an initial course of antithymocyte globulin (ATG) plus cyclosporine has not yet been established. We compared the effectiveness of allogeneic hematopoietic stem cell transplantation (allo-HSCT) (n = 36) with repeated immunosuppressive therapy (IST) (n = 33) for relapsed/refractory SAA between 2007 and 2022. In the IST group, patients were retreated with ATG (n = 16) or high-dose cyclophosphamide (n = 17). The overall response rate was 57.6% at 6 months and 60.6% at 12 months. In the allo-HSCT group, patients received a transplant from a matched sibling donor (n = 6), matched unrelated donor (n = 7), or haploidentical donor (n = 23). All patients achieved neutrophil engraftment, and there were no cases of primary graft failure. The cumulative incidences (CIs) of grades II–IV and III–IV acute graft-versus-host disease (GVHD) were 36.1% ± 0.7% and 13.9% ± 0.3% at day +100, respectively. The 4-year CI of chronic GVHD (cGVHD) was 36.2% ± 0.7%, with moderate to severe cGVHD at 14.9% ± 0.4%. Compared with IST, HSCT recipients showed much higher hematologic recovery rate at 3, 6, and 12 months (63.9%, 83.3%, and 86.1%, respectively, p < 0.001). The estimated 4-year overall survival (OS) (79.8% ± 6.8% vs. 80.0% ± 7.3%, p = 0.957) was similar; however, the failure-free survival (FFS) was significantly better in the HSCT group (79.8% ± 6.8% vs. 56.6% ± 8.8%, p = 0.049). Of note, children in the HSCT cohort were all alive without treatment failures, exhibiting superior OS (100% vs. 50.0% ± 17.7%, p = 0.004) and FFS (100% vs. 50.0% ± 17.7%, p = 0.004) than children in the IST cohort. Subgroup analysis revealed that younger patients (age ≤ 35 years), especially children, and those with refractory SAA benefited more from HSCT. Therefore, for these patients, salvage HSCT may be more preferable than a second course of IST.

Abstract The mechanism involved in major depressive disorder (MDD) is well‐studied but the mechanistic origin of the heterogeneous antidepressant effect remains largely unknown. Single‐cell RNA‐sequencing (scRNA‐seq) and assay for transposase‐accessible chromatin using sequencing (ATAC‐seq) on peripheral blood mononuclear cells from 8 healthy individuals and 8 MDD patients before or after 12 weeks of antidepressant treatment is performed. scRNA‐seq analysis reveals a lower proportion of naive T cells, particularly CD4+ naive T cells, in MDD patients compared to controls, and in nonresponders versus responders at the baseline. Flow cytometry data analysis of an independent cohort of 35 patients and 40 healthy individuals confirms the findings. Enrichment analysis of differentially expressed genes indicated obvious immune activation in responders. A specific activated CD4+ naive T population in responders characterized by enhanced mitogen‐activated protein kinases (MAPK) pathway is identified. E‐twenty six (ETS) is proposed as an upstream regulator of the MAPK pathway and heterogeneous differentiation in activated CD4+ naive T population is associated with the response to antidepressant treatment in MDD patients. A distinct immune feature manifested by CD4+ naive T cells during antidepressant treatment in MDD is identified. Collectively, this proposes the molecular mechanism that underlies the heterogeneous antidepressant outcomes for MDD.

Biochar (BC) is widely utilized as a soil amendment; however, for widely distributed seasonally frozen soils, the effect of BC on soil and the optimal utilization of BC during the freeze‒thaw process are still unclear. In this study, the effects of freeze‒thaw aged biochar (FT-BC) and BC on soil properties and wheat cultivation were systematically investigated, and the underlying interaction mechanism between BC and soil was explored. The results show that FT-BC dramatically reduces the adverse effects of freeze‒thaw cycles on soil, enhances wheat growth, and increases dry matter yield by 17.5 %, which is mainly attributed to the ability of FT-BC to maintain soil structure, reduce water loss rates to below 0.20 g/h, and decrease nitrogen leaching by more than 20 % during freeze‒thaw cycles. Additionally, fresh BC had a greater effect on the fixation of cadmium than FT-BC in the soil, reducing its accumulation in wheat by 22.5 %. Multiple characterizations revealed that the freeze‒thaw process increased the porosity and specific surface area of FT-BC, providing more sites for water and nitrogen adsorption, whereas the dissolved organic matter released from fresh BC had a better ability to trap cadmium. These findings provide insights into the interactions between BC and soil components during the freeze‒thaw process and suggest the optimized utilization of fresh BC and FT-BC for different soil repair purposes.

Alveolar bone defect repair remains a persistent clinical challenge for periodontitis treatment. The use of peripheral functional seed cells is a hot topic in periodontitis. Herein, we explored the cellular behaviors and osteogenic ability of adipose-derived mesenchymal stem cells (ADSCs) treated with black phosphorus quantum dots (BPQDs). Additionally, macrophage polarization, osteogenic effects and angiogenesis were investigated through the paracrine pathway regulated by BPQD-modified ADSCs. Our results demonstrated that BPQDs showed good biocompatibility with ADSCs and BPQD-modified ADSCs could improve the bone repair in vivo inflammatory microenvironment by regulating osteogenesis and osteoimmunomodulation. The BPQDs increased the osteogenic differentiation of ADSCs via the Wnt/β-catenin and BMP2/SMAD5/Runx2 signaling pathway. In addition, BPQD-modified ADSCs promoted the osteogenic effect of BMSCs and facilitated the polarization of macrophages from M1 towards M2 phenotype transformation through the paracrine pathway in the periodontitis microenvironment. This strategy provides a novel idea for treatment of alveolar bone defects for periodontitis in the foreseeable future.

Abstract cAMP responsive element binding protein 3 (CREB3), belonging to bZIP family, was reported to play multiple roles in various cancers, but its role in hepatocellular carcinoma (HCC) is still unclear. cAMP responsive element binding protein 3 like 3 (CREB3L3), another member of bZIP family, was thought to be transcription factor (TF) to regulate hepatic metabolism. Nevertheless, except for being TFs, other function of bZIP family were poorly understood. In this study, we found CREB3 inhibited growth and metastasis of HCC in vitro and in vivo. RNA sequencing indicated CREB3 regulated AKT signaling to influence HCC progression. Mass spectrometry analysis revealed CREB3 interacted with insulin receptor (INSR). Mechanistically, CREB3 suppressed AKT phosphorylation by inhibiting the interaction of INSR with insulin receptor substrate 1 (IRS1). In our study, CREB3 was firstly proved to affect activation of substrates by interacting with tyrosine kinase receptor. Besides, CREB3 could act as a TF to transactivate RNA‐binding motif protein 38 (RBM38) expression, leading to suppressed AKT phosphorylation. Rescue experiments further confirmed the independence between the two functional manners. In conclusion, CREB3 acted as a tumor suppressor in HCC, which inhibited AKT phosphorylation through independently interfering interaction of INSR with IRS1, and transcriptionally activating RBM38.

Abstract Background Patients diagnosed with advanced stage cancer face an elevated risk of suicide. We aimed to develop a suicidal ideation (SI) risk prediction model in patients with advanced cancer for early warning of their SI and facilitate suicide prevention in this population. Patients and Methods We consecutively enrolled patients with multiple types of advanced cancers from 10 cancer institutes in China from August 2019 to December 2020. Demographic characteristics, clinicopathological data, and clinical treatment history were extracted from medical records. Symptom burden, psychological status, and SI were assessed using the MD Anderson Symptom Inventory (MDASI), Hospital Anxiety and Depression Scale (HADS), and Patient Health Questionnaire‐9 (PHQ‐9), respectively. A multivariable logistic regression model was employed to establish the model structure. Results In total, 2814 participants were included in the final analysis. Nine predictors including age, sex, number of household members, history of previous chemotherapy, history of previous surgery, MDASI score, HADS‐A score, HADS‐D score, and life satisfaction were retained in the final SI prediction model. The model achieved an area under the curve (AUC) of 0.85 (95% confidential interval: 0.82–0.87), with AUCs ranging from 0.75 to 0.95 across 10 hospitals and higher than 0.83 for all cancer types. Conclusion This study built an easy‐to‐use, good‐performance predictive model for SI. Implementation of this model could facilitate the incorporation of psychosocial support for suicide prevention into the standard care of patients with advanced cancer.

Summary: Compared to traditional methods, using machine learning to assess or predict the odor of molecules can save costs in various aspects. Our research aims to collect molecules with coffee odor and summarize the regularity of these molecules, ultimately creating a binary classifier that can determine whether a molecule has a coffee odor. In this study, a total of 371 coffee-odor molecules and 9,700 non-coffee-odor molecules were collected. The Knowledge-guided Pre-training of Graph Transformer (KPGT), support vector machine (SVM), random forest (RF), multi-layer perceptron (MLP), and message-passing neural networks (MPNN) were used to train the data. The model with the best performance was selected as the basis of the predictor. The prediction accuracy value of the KPGT model exceeded 0.84 and the predictor has been deployed as a webserver PredCoffee.

Abstract Objectives Patients with advanced colorectal cancer (CRC) have multiple concurrent physical and psychological symptoms. This study aimed to explore the relationship between anxiety, depression, and symptom burden in advanced CRC. Methods A multicenter cross‐sectional study was conducted in 10 cancer centers from geographically and economically diverse sites in China. A total of 454 patients with advanced CRC completed the Hospital Anxiety and Depression Scale and the MD Anderson Symptom Inventory. Multiple regression analysis was applied to explore the relationship between anxiety, depression and symptom burden. Results About one‐third of the patients showed symptoms of anxiety or depression. Patients with anxiety or depression reported significantly higher symptom burden than those without (p

The widely used Shack–Hartmann wavefront sensor (SHWFS) is a wavefront measurement system. Its measurement accuracy is limited by the reference wavefront used for calibration and also by various residual errors of the sensor itself. In this study, based on the principle of spherical wavefront calibration, a pinhole with a diameter of 1 µm was used to generate spherical wavefronts with extremely small wavefront errors, with residual aberrations of 1.0 × 10−4 λ RMS, providing a high-accuracy reference wavefront. In the first step of SHWFS calibration, we demonstrated a modified method to solve for three important parameters (f, the focal length of the microlens array (MLA), p, the sub-aperture size of the MLA, and s, the pixel size of the photodetector) to scale the measured SHWFS results. With only three iterations in the calculation, these parameters can be determined as exact values, with convergence to an acceptable accuracy. For a simple SHWFS with an MLA of 128 × 128 sub-apertures in a square configuration and a focal length of 2.8 mm, a measurement accuracy of 5.0 × 10−3 λ RMS was achieved across the full pupil diameter of 13.8 mm with the proposed spherical wavefront calibration. The accuracy was dependent on the residual errors induced in manufacturing and assembly of the SHWFS. After removing these residual errors in the measured wavefront results, the accuracy of the SHWFS increased to 1.0 × 10−3 λ RMS, with measured wavefronts in the range of λ/4. Mid-term stability of wavefront measurements was confirmed, with residual deviations of 8.04 × 10−5 λ PV and 7.94 × 10−5 λ RMS. This study demonstrates that the modified calibration method for a high-accuracy spherical wavefront generated from a micrometer-scale pinhole can effectively improve the accuracy of an SHWFS. Further accuracy improvement was verified with correction of residual errors, making the method suitable for challenging wavefront measurements such as in lithography lenses, astronomical telescope systems, and adaptive optics.

Abstract The 2022 European LeukemiaNet (ELN) updated the previous risk classification published in 2017 but the prognostic significance for allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. We enrolled 600 acute myeloid leukemia (AML) patients who underwent allo-HSCT to validate ELN-2022 genetic risk system and compared it with ELN-2017. There were 214 (35.67%), 162 (27.0%), and 224 (37.33%) patients in ELN-2022 favorable-, intermediate-, and adverse-risk group respectively and 86 patients (14.33%) experienced a shift in risk stratification compared to ELN-2017. Median and maximum follow-up time were 2.89 (95% CI 2.67 to 3.03) years and 8.78 years. The median overall survival (OS) was 73.8% (95% CI 67.5% to 80.3%), 63.9% (95% CI 56.7% to 72.0%) and 57.6% (95% CI 50.4% to 65.9%) in ELN-2022 favorable-, intermediate-, and adverse-risk group (P

Abstract Metastatic breast cancer could cause various psychological symptoms. Managing Cancer and Living Meaningfully (CALM) is a brief, manualized psychotherapy that has been validated for advanced cancer patients. We conducted a pilot randomized control trial (RCT) to verify the feasibility and preliminary efficacy of CALM therapy in this population. Patients who met the inclusion criteria were randomly assigned into CALM or Wait-list Control (WLC) groups. Patients in the CALM group received CALM therapy and usual care; patients in WLC group first received usual care and then underwent CALM therapy after completing all assessments. All patients were asked to complete three assessments: T0(baseline), T1(3 months), and T2(6 months). The primary outcomes was death anxiety; other outcomes were depression, distress, suicide ideation, attachment security, spiritual well-being and quality of life at the end of life. Analysis of Covariance (ANCOVA) and t-test were used for statistics analysis. Thirty-six patients were randomly assigned to either of the two groups, with 34 patients completing the three assessments. At six months, we found significant between group differences in suicide ideation, distress, and life completion between the CALM and WLC groups. At T2, patients in CALM group reported lower levels of depression (F = 5.016, p = 0.033, partial η2 = 0.143), distress (F = 7.969, p = 0.010, partial η2 = 0.257), attachment avoidance (F = 4.407, p = 0.044, partial η2 = 0.128), and better sense of life completion (F = 5.493, p = 0.026, partial η2 = 0.155) than patients in the WLC group. Compared with results of the T0 assessments, we found significant differences in socres for depression (T2&T0, t = − 2.689, p = 0.011, Cohen’s d = 0.940) and distress (T2&T0, t = − 2.453, p = 0.022, Cohen’s d = 0.965) between the two groups. CALM therapy was well received by the study population, and CALM therapy can reduce depression, distress, attachment avoidance while improving quality of life in Chinese metastatic breast cancer patients. A Phase III RCT was recommended to verify the impact of CALM therapy on psychological burden and survival in this population. Trial registration: This study is part of the “Preliminary application study for Managing Cancer and Living Meaningfully (CALM) therapy in Chinese advanced cancer patients” clinical trial, with the Trial Registration Number of ChiCTR1900023129 (13/05/2019) in the Chinese Clinical Trial Registry (ChiCTR) website. ( https://www.chictr.org.cn/index.html ).

Abstract Background/purpose This study compared the clinical efficacy and safety of laparoscopic versus open resection for hilar cholangiocarcinoma (HCCA) and analyzed potential prognostic factors. Methods The study included patients who underwent HCCA resection at our center from March 2012 to February 2022. Perioperative complications and postoperative prognosis were compared between the laparoscopic surgery (LS) and open surgery (OS) groups. Results After screening 313 HCCA patients, 68 patients were eligible for the study in the LS group (n = 40) and OS group (n = 28). Kaplan-Meier survival curve analysis revealed that overall survival > 2 years and 3-year disease-free survival (DFS) were more common in the LS than OS group, but the rate of 2-year DFS was lower in the LS group than OS group. Cox multivariate regression analysis revealed age (< 65 years), radical resection, and postoperative adjuvant therapy were associated with reduced risk of death (hazard ratio [HR] = 0.380, 95% confidence interval [CI] = 0.150–0.940, P = 0.036; HR = 0.080, 95% CI = 0.010–0.710, P = 0.024 and HR = 0.380, 95% CI = 0.150–0.960, P = 0.040), whereas preoperative biliary drainage was an independent factor associated with increased risk of death (HR = 2.810, 95% CI = 1.130–6.950, P = 0.026). Perineuronal invasion was identified as an independent risk factor affecting DFS (HR = 5.180, 95% CI = 1.170–22.960, P = 0.030). Conclusions Compared with OS, laparoscopic HCCA resection does not significantly differ in terms of clinical efficacy. Age (

Abstract Background Little is understood about the association between psychosomatic symptoms and advanced cancer among older Chinese patients. Methods This secondary analysis was part of a multicenter cross-sectional study based on an electronic patient-reported outcome platform. Patients with advanced cancer were included between August 2019 and December 2020 in China. Participants (over 60 years) completed the MD Anderson Symptom Inventory (MDASI) and Hospital Anxiety and Depression Scale (HADS) to measure symptom burden. Network analysis was also conducted to investigate the network structure, centrality indices (strength, closeness, and betweenness) and network stability. Results A total of 1022 patients with a mean age of 66 (60–88) years were included; 727 (71.1%) were males, and 295 (28.9%) were females. A total of 64.9% of older patients with advanced cancer had one or more symptoms, and up to 80% had anxiety and depression. The generated network indicated that the physical symptoms, anxiety and depression symptom communities were well connected with each other. Based on an evaluation of the centrality indices, ‘distress/feeling upset’ (MDASI 5) appears to be a structurally important node in all three networks, and ‘I lost interest in my own appearance’ (HADS-D4) had the lowest centrality indices. The network stability was relatively high (> 0.7). Conclusion The symptom burden remains high in older patients with advanced cancer in China. Psychosomatic symptoms are highly interactive and often present as comorbidities. This network can be used to provide targeted interventions to optimize symptom management in older patients with advanced cancer in China. Trial registration Chinese Clinical Trial Registry (ChiCTR1900024957), registered on 06/12/2020.

Abstract Background SLC25A17, a peroxisomal solute carrier, has been implicated in various physiological and pathological processes. However, its precise roles and underlying mechanisms in triple-negative breast cancer (TNBC) remain incompletely understood. Methods The expression and survival data of breast cancer were derived from TCGA and GEO databases. A variety of in vitro assays were conducted, including proliferation, apoptosis, cell cycle, migration, and invasion. Reactive oxygen species (ROS) were measured by immunofluorescence microscopy and flow cytometry. The levels of autophagy were assessed by mRFP-GFP-LC3 confocal microscopy scanning, western blotting, and electron microscopy. Results SLC25A17 was highly expressed in breast cancer tissues, which was found to be associated with unfavorable prognosis. Functional assays demonstrated that SLC25A17 knockdown suppressed proliferation, epithelial-mesenchymal transition (EMT), migration, and invasion. Moreover, it prompted apoptosis and autophagy. On the other hand, SLC25A17 knockdown promoted autophagy through triggering ROS accumulation, which was counteracted by N-acetyl-l-cysteine (NAC). Furthermore, the pro-apoptotic effect of SLC25A17 knockdown was reversed when treated with autophagy inhibitor 3-MA in TNBC cells, suggesting that SLC25A17 knockdown-induced autophagic cell death. Mechanistically, SLC25A17 performed its function through regulation JAK2/STAT3 signaling in TNBC. In a nude mice xenograft study, SLC25A17 knockdown markedly decreased breast tumor growth and metastasis. Conclusion SLC25A17 up-regulation may be a critical factor driving TNBC progression by modulating ROS production and autophagy. Consequently, targeting SLC25A17 could be an effective therapeutic strategy against TNBC.

Abstract G protein-coupled receptor 55 (GPR55) has been thought to be a putative cannabinoid receptor. However, little is known about its functional role in cannabinoid action and substance use disorders. Here we report that GPR55 is predominantly found in glutamate neurons in the brain, and its activation reduces self-administration of cocaine and nicotine in rats and mice. Using RNAscope in situ hybridization, GPR55 mRNA was identified in cortical vesicular glutamate transporter 1 (VgluT1)-positive and subcortical VgluT2-positive glutamate neurons, with no detection in midbrain dopamine (DA) neurons. Immunohistochemistry detected a GPR55-like signal in both wildtype and GPR55-knockout mice, suggesting non-specific staining. However, analysis using a fluorescent CB1/GPR55 ligand (T1117) in CB1-knockout mice confirmed GPR55 binding in glutamate neurons, not in midbrain DA neurons. Systemic administration of the GPR55 agonist O-1602 didnt impact ∆9-THC-induced analgesia, hypothermia and catalepsy, but significantly mitigated cocaine-enhanced brain-stimulation reward caused by optogenetic activation of midbrain DA neurons. O-1602 alone failed to alter extracellar DA, but elevated extracellular glutamate, in the nucleus accumbens. In addition, O-1602 also demonstrated inhibitory effects on cocaine or nicotine self-administration under low fixed-ratio and/or progressive-ratio reinforcement schedules in rats and wildtype mice, with no such effects observed in GPR55-knockout mice. Together, these findings suggest that GPR55 activation may functionally modulate drug-taking and drug-seeking behavior possibly via a glutamate-dependent mechanism, and therefore, GPR55 deserves further study as a new therapeutic target for treating substance use disorders.

Abstract Xanthine oxidase (XO) is a crucial enzyme in the development of hyperuricemia and gout. This study focuses on LWM and ALPM, two food-derived inhibitors of XO. We used molecular docking to obtain three systems and then conducted 200 ns molecular dynamics simulations for the Apo, LWM, and ALPM systems. The results reveal a stronger binding affinity of the LWM peptide to XO, potentially due to increased hydrogen bond formation. Notable changes were observed in the XO tunnel upon inhibitor binding, particularly with LWM, which showed a thinner, longer, and more twisted configuration compared to ALPM. The study highlights the importance of residue F914 in the allosteric pathway. Methodologically, we utilized the perturbed response scan (PRS) based on Python, enhancing tools for MD analysis. These findings deepen our understanding of food-derived anti-XO inhibitors and could inform the development of food-based therapeutics for reducing uric acid levels with minimal side effects.

Abstract Autoimmune congenital heart block (ACHB) is a passively acquired immune-mediated disease characterized by the presence of maternal antibodies against components of the Ro/SSA and La/SSB ribonucleoprotein complex that mainly affects the cardiac conducting system. ACHB occurs in 2% of women with positive anti-Ro/SSA and anti-La/SSB antibodies and causes a high risk of intrauterine fetal death, neonatal mortality, and long-term sequelae. In this review, we first describe a case of ACHB to provide preliminary knowledge. Then, we discuss the possible pathogenic mechanisms of ACHB; summarize the pregnancy management of patients with positive anti-Ro/SSA and anti-La/SSB antibodies and/or rheumatic diseases, the prevention of ACHB, and the treatment of ACHB fetuses; and propose routine screening of these antibodies for the general population. Careful follow-up, which consists of monitoring the fetal heart rate, is feasible and reassuring for pregnant women with positive anti-Ro/SSA and/or anti-La/SSB antibodies to lower the risk of ACHB in fetuses. Moreover, maternal administration of hydroxychloroquine may be useful in preventing ACHB in pregnant women with anti-Ro/SSA and/or anti-La/SSB antibodies.

Abstract Objective The aim of this study was to assess the accuracy and test-retest reliability of a wearable inertial measurement unit (IMU) system for gait analysis in healthy female compared to a gold-standard optoelectronic motion capture (OMC) system. Methods In our study, we collected data from 5 healthy young females. Participants were attached with markers from both the OMC system and the IMU system simultaneously. Data was collected when participants walked on a 7 m walking path. Each participant performed 50 repetitions of walking on the path. To ensure the collection of complete gait cycle data, a gait cycle was considered valid only if the participant passed through the center of the walking path at the same time that the OMC system detected a valid marker signal. As a result, 5 gait cycles that met the standards of the OMC system were included in the final analysis. The stride length, cadence, velocity, stance phase and swing phase of the spatio-temporal parameters were included in the analysis. A generalized linear mixture model was used to assess the repeatability of the two systems. The Wilcoxon rank-sum test for continuous variables was used to compare the mean differences between the two systems. For evaluating the reliability of the IMU system, we calculated the Intra-class Correlation Coefficient (ICC). Additionally, Bland-Altman plots were used to compare the levels of agreement between the two systems. Results The measurements of Spatio-temporal parameters, including the stance phase (P = 0.78, 0.13, L-R), swing phase (P = 0.78, 0.13, L-R), velocity (P = 0.14, 0.13, L-R), cadence (P = 0.53, 0.22, L-R), stride length (P = 0.05, 0.19, L-R), by the IMU system and OMC system were similar. Which suggested that IMU and OMC systems could be used interchangeably for gait measurements. The intra-rater reliability showed an excellent correlation for the stance phase, swing phase, velocity and cadence (Intraclass Correlation Coefficient, ICC > 0.9) for both systems. However, the correlation of stride length was poor (ICC = 0.36, P = 0.34, L) to medium (ICC = 0.56, P = 0.22, R). Additionally, the measurements of IMU systems were repeatable. Conclusions The results of IMU system and OMC system shown good repeatability. Wearable IMU system could analyze gait data accurately. In particular, the measurement of stance phase, swing phase, velocity and cadence showed excellent reliability. IMU system provided an alternative measurement to OMC for gait analysis. However, the measurement of stride length by IMU needs further consideration.

Walnut is an important economic tree species that is susceptible to osmotic stress. Scientific cultivation management is an important way to improve the yield and quality of walnuts, which requires understanding the regulatory mechanisms in response to osmotic stress. Therefore, in this study, 15 protein phosphatase 2A (PP2A) genes were identified from the walnut transcriptome (named JrPP2A01~15) and their potential function responses to osmotic stress were elucidated. The open reading frame (ORF) of JrPP2A01~15 ranges from 651 to 1,764 bp in length, the molecular weight of the encoded proteins are 24.15−65.61 kDa, and the theoretical isoelectric points are 4.80−8.37. These JrPP2As were unevenly distributed on 10 chromosomes and divided into five groups based on the composition of conserved domains, motifs, and exon/intron organizations. The five groups are JrPP2AAs, JrPP2AB's, JrPP2AB''s, JrPP2AB55s, and JrPP2ACs, including 1, 5, 2, 3, and 4 members, accordingly. The cis-elements in JrPP2As' promoters were involved in responses to hormone and abiotic stress. Most JrPP2A genes, excluding JrPP2A01, JrPP2A02, JrPP2A05, JrPP2A06, and JrPP2A13, could be induced significantly by PEG6000, NaCl, CaCl2 and ABA. JrPP2A02, JrPP2A05, JrPP2A07, JrPP2A09, and JrPP2A14, could independently interact with a bZIP transcription factor JrVIP1. Moreover, overexpression of JrPP2A07, JrPP2A09, and JrPP2A14 could significantly decrease ROS accumulation while increasing calcium (Ca) uptake exposed to PEG6000 and NaCl stresses, which was mediated by exogenous CaCl2 and ABA. These results suggested that JrPP2A genes play potential key roles in walnut response to drought and salt-inducing osmotic stress involving Ca- and ABA-dependent signaling pathways.

Landslide susceptibility mapping (LSM) is of great significance in geohazard early warning and prevention. The existing LSM methods mostly used traditional static landslide conditioning factors (LCFs), which only considered the spatial features of single-pixel neighborhoods and could not extract the time-series dynamic features of developing landslides, resulting in low accuracy and insufficient reliability of LSM. To solve this problem, this study proposes to introduce time-series rainfall factors based on the traditional static factors and construct an integrated time-series dynamic neural network (TSDNN) model for LSM. A convolutional neural network (CNN) adding time-distributed convolution and a bidirectional long and short-term memory neural network is utilized to extract time-series rainfall features, and a multiscale convolutional neural network (MSCNN) is utilized to extract static features of the static LCFs. In this study, multicollinearity analysis and geodetector are utilized to analyze the LCFs. Multiple evaluation metrics are utilized to analyze the proposed model performance. The results indicate that the overall accuracy has improved by introducing time-series rainfall factors, and the susceptibility area of actual predicted is more refined. The study indicates that significant advantages of the proposed TSDNN model are over models [CNN, MSCNN, random forest (RF)] when processing combined static and rainfall data. This is notably evident that the accuracy is enhanced by 12.9%, 10.7%, and 11.4% compared to CNN, MSCNN, and RF models in the receiver operating characteristic curve analysis, respectively. Moreover, two typical areas containing three recent landslide events validate the reliability of the proposed TSDNN model. The proposed network model framework for LSM considering time-series rainfall factors can provide new ideas and key technical support for landslide disaster prevention.

Thaw slump susceptibility mapping (TSSM) of Qinghai–Tibet railway corridor (QTRC) is the prerequisite and basis for disaster assessment and prevention of permafrost projects. The objective of this article is to construct ensemble learning models based on single classifier models to generate the TSSM of the QTRC, compare and verify the performance of the models, and further explore the relationship between the high susceptibility area and environmental factors of the QTRC. The collinearity analysis was carried out by selecting 14 thaw slump conditioning factors (TSCFs). We used the balance bagging method for sample optimization, and the dataset was divided into 70% training set and 30% verification set. Convolutional neural network, multilayer perceptron, support vector regression, random forest single classifiers were selected to construct blending and stacking ensemble learning models for the TSSM. The results showed that there was no collinearity among the 14 TSCFS. The comparison of model performance revealed that all models had good performance, but the constructed stacking and blending ensemble learning models had stable performance and high prediction accuracy for TSSM. The stacking ensemble learning model had the best effect, and the area under curve value of receiver operating characteristic curve reached 0.9607. It showed that the generated TSSM of QTRC based on stacking ensemble learning model had the highest reliability. The QTRC has local areas with high thaw slump susceptibility, mainly concentrated in the permafrost areas with high altitude, high slope, adjacent faults, sparse vegetation, ice and snow and the more cumulative precipitation.

Surface deformation of alpine peatland in China has an important effect on runoff and is of great significance for wetland ecosystem protection. However, spatio-temporal characteristics of alpine peatland surface deformation in China lack systematic studies, and the driving mechanism is not yet clear. In this study, we selected the alpine peatland of Maduo County in China as the research object, surface deformation of peatland based on the small baseline subset radar interferometry technique was obtained, we analyzed spatio-temporal deformation characteristics and patterns of peatland, explored the driving mechanism of the peatland surface deformation with single-factor and multifactor combinations of Geo-detector, respectively. The results showed that the overall subsidence rates of peatlands in Maduo County, China slowed down year by year from 2018 to 2020, but there was seasonal freezing and thawing, subsidence rates of peatlands at high elevation and high slopes were stable, peatlands at low elevation and low slope were vulnerable to disturbance, subsidence rates are largest. Maliecuo, Bailongqu, and Gaerlawangzang regions were serious subsidence, the maximum subsidence rate was 159 mm/year. Meteorological factors and geological conditions were the main reasons for the surface deformation of alpine peatland in Maduo County, China. This study provides a theoretical basis for the conservation and restoration of peatland ecosystems in the alpine regions of China.

The ancient Suoertou landslide seriously threatens the surrounding population's lives and property. Monitoring and predicting this landslide is crucial to ensure the affected areas’ safety. The previous research on the landslide's displacement characteristics and mechanisms has lacked detailed analyses. In addition, its future development trends must be understood. Therefore, we conducted a detailed analysis of the ancient Suoertou landslide's displacement characteristics and mechanisms using small baseline subset interferometric synthetic aperture radar monitoring results from 2018 to 2023. Furthermore, by applying a gated recurrent unit prediction mode that incorporates the refined displacement characteristics and mechanisms, we forecasted the landslide's displacement trends. The results show that this landslide is currently undergoing overall slow displacement with violent fluctuations in localized areas. Tectonic movement, precipitation, human activities, river erosion, and other factors interact, forming a vicious development displacement mechanism. According to our prediction, the displacement of this landslide will be in a trend of fluctuating increase from June 2023 to June 2024. In particular, the local area will undergo abnormal displacement acceleration. The results of the current research provide a scientific basis upon which to monitor landslides, promote their management, and reduce the risk of losses due to landslide disasters.

Bupleurum jeholense Nakai (Apioideae, Apiaceae), originally found in the Wuling Mountain of China, was initially described as a species but later treated as a variety of B. sibiricum Vest ex Spreng. However, researchers have recently found that it is more closely related to B. chinense DC. In this study, we conducted morphological and phylogenetic analyses as well as chromosome counting to determine the taxonomic status of B. sibiricum var. jeholense (Nakai) Chu. Our results showed that B. sibiricum var. jeholense and B. chinense share common features (i.e., bracteoles 5 and stem solid) that distinguish both from B. sibiricum var. sibiricum. The chromosome number of B. sibiricum var. jeholense was found to be the same as in B. chinense (i.e., 2n = 12), whereas the chromosome number of B. sibiricum var. sibiricum was 64. A phylogenetic tree based on complete chloroplast genome data revealed a close relationship between B. sibiricum var. jeholense and B. chinense. Finally, B. sibiricum var. jeholense and B. chinense were mainly found to differ in plant height, number of stems, and middle stem leaves. Based on this evidence, we propose a new combination: Bupleurum chinense var. jeholense (Nakai) Q.R.Liu & L.H.Wang.

Abstract Purpose The health of rhizosphere soil microorganisms is an important indicator to evaluate soil quality. Therefore, understanding the response of rhizosphere soil microorganisms to tobacco crop succession is crucial for promoting the sustainable development of agriculture. Methods The microbial diversity and community structure of rhizosphere soil in continuous cropping and non-cropped tobacco for 7 years were analyzed by the Illumina platform. Result (1) Continuous cropping tobacco cause rhizosphere soil acidification and reduction in alkaline nitrogen (AN) and soil organic matter (SOM). (2) Continuous cropping tobacco reduces the diversity of rhizosphere soil microbial communities, increasing harmful functional microorganisms and declining beneficial ones. (3) The abundance of bacteria that perform nitrification and saprophytic fungi in the rhizosphere soil of continuous cropping areas decreases, inhibiting carbon and nitrogen cycling processes. (4) The composition and diversity of the soil rhizosphere microbial community are affected by the imbalance in the physicochemical property of the rhizosphere. Conclusion Continuous cropping tobacco cause rhizosphere soil acidification and nutrient imbalance, and the carbon and nitrogen cycles involved in microorganisms were damaged. Furthermore, the decreased diversity of rhizosphere soil microorganisms and the increased abundance of pathogenic fungi contribute to the continuous cropping obstacles of tobacco.

In response to the issues of relatively low image contrast, blurry boundaries of infrared small targets, and various environmental noise interferences in thermal imaging systems, resulting in reduced target recognition rates and tracking effectiveness. This paper proposes an infrared target image recognition algorithm based on fuzzy comprehensive assessment. Built upon infrared image sequences captured by an on-board thermal imager, the algorithm employs grayscale processing, neighborhood mean filtering, and second-order difference method to filter and enhance the infrared target images. This process improves the quality of infrared target images and enhances the contrast between targets and backgrounds. The algorithm utilizes the maximum interclass variance method for segmenting the infrared target images, combining it with the Canny operator to extract target edges, thereby obtaining clearer details of the infrared target edges. Finally, based on the extracted target feature information, the algorithm calculates the confidence of each marked region, establishes the membership function of target likelihood, employs a comprehensive weighted approach to construct the target confidence function, and compares the confidence of marked regions with that of the template image to achieve precise target recognition. Experimental validation against theoretical methods and comparisons with other approaches demonstrate the effectiveness and feasibility of the proposed method, providing theoretical support for reliable target tracking in electro-optical imaging systems.

Abstract Osteosarcoma (OS) is one of the most prevalent bone tumors in adolescents, and the correlation between aging and OS remains unclear. Currently, few accurate and reliable biomarkers have been determined for OS prognosis. To address this issue, we carried out a detailed bioinformatics analysis based on OS with data from the Cancer Genome Atlas data portal and Human Aging Genomic Resources database, as well as in vitro experiments. A total of 88 OS samples with gene expression profiles and corresponding clinical characteristics were obtained. Through univariate Cox regression analysis and survival analysis, 10 aging-associated survival lncRNAs (AASRs) were identified to be associated with the overall survival of OS patients. Based on the expression levels of the 10 AASRs, the OS patients were classified into two clusters (Cluster A and Cluster B). Cluster A had a worse prognosis, while Cluster B had a better prognosis. Then, 5 AASRs were ultimately included in the signature through least absolute shrinkage and selection operator-Cox regression analysis. Kaplan‒Meier survival analysis verified that the high-risk group exhibited a worse prognosis than the low-risk group. Furthermore, univariate and multivariate Cox regression analyses confirmed that the riskScore was an independent prognostic factor for OS patients. Subsequently, we discovered that the risk signature was correlated with the properties of the tumor microenvironment and immune cell infiltration. Specifically, there was a positive association between the risk model and naïve B cells, resting dendritic cells and gamma delta T cells, while it was negatively related to CD8+ T cells. Finally, in vitro experiments, we found that UNC5B-AS1 inhibited OS cells from undergoing cellular senescence and apoptosis, thereby promoting OS cells proliferation. In conclusion, we constructed and verified a 5 AASR-based signature, that exhibited excellent performance in evaluating the overall survival of OS patients. In addition, we found that UNC5B-AS1 might inhibit the senescence process, thus leading to the development and progression of OS. Our findings may provide novel insights into the treatment of OS patients.

Abstract Background Pyroptosis, mediated by gasdermins with the release of multiple inflammatory cytokines, has emerged as playing an important role in targeted therapy and immunotherapy due to its effectiveness at inhibiting tumor growth. Melanoma is one of the most commonly used models for immunotherapy development, though an inadequate immune response can occur. Moreover, the development of pyroptosis-related therapy and combinations with other therapeutic strategies is limited due to insufficient understanding of the role of pyroptosis in the context of different tumor immune microenvironments (TMEs). Methods Here, we present a computational model (pyroptosis-related gene score, PScore) to assess the pyroptosis status. We applied PScore to 1388 melanoma samples in our in-house cohort and eight other publicly available independent cohorts and then calculated its prognostic power of and potential as a predictive marker of immunotherapy efficacy. Furthermore, we performed association analysis for PScore and the characteristics of the TME by using bulk, single-cell, and spatial transcriptomics and assessed the association of PScore with mutation status, which contributes to targeted therapy. Results Pyroptosis-related genes (PRGs) showed distinct expression patterns and prognostic predictive ability in melanoma. Most PRGs were associated with better survival in metastatic melanoma. Our PScore model based on genes associated with prognosis exhibits robust performance in survival prediction in multiple metastatic melanoma cohorts. We also found PScore to be associated with BRAF mutation and correlate positively with multiple molecular signatures, such as KRAS signaling and the IFN gamma response pathway. Based on our data, melanoma with an immune-enriched TME had a higher PScore than melanoma with an immune-depleted or fibrotic TME. Additionally, monocytes had the highest PScore and malignant cells and fibroblasts the lowest PScore based on single-cell and spatial transcriptome analyses. Finally, a higher PScore was associated with better therapeutic efficacy of immune checkpoint blockade, suggesting the potential of pyroptosis to serve as a marker of immunotherapy response. Conclusions Collectively, our findings indicate that pyroptosis is a prognostic factor and is associated with the immune response in metastatic melanoma, as based on multiomics data. Our results provide a theoretical basis for drug combination and reveal potential immunotherapy response markers.

Abstract In the context of automated driving, the connected and automated vehicles (CAVs) technology unlock the energy saving potential. This paper develops an LSTM‐based deep learning framework for eco‐driving adaptive identification on Intelligent vehicle multivariate time series data. The framework can be adapted for Driver Assistance Systems (DAS) to reduce fuel consumption. Specifically, considering overtaking on rural road is a critical maneuver for operation and has potential to reduce consumption, a simulated driving experiment with 30 participants was conducted to collect the multivariate time series data of the overtaking operation behaviors in conditional automation driving. Driving behaviors were classified into eco‐driving operation behaviors and high fuel consumption operation behaviors based on fuel consumption calculated by using vehicle specific power (VSP). Significance analysis based on linear regression was adopted to identify operation behaviors, and an eco‐driving behavior identification model was established with the use of long short‐term memory (LSTM) for multivariate classification theory. Meanwhile, the other four classification algorithms were used to establish identification models for comparison. The results indicated that the gear position, lane position, the acceleration pedal depth, the clutch pedal depth, and the brake pedal depth had a significant influence on fuel consumption. The eco‐driving behavior identification model of overtaking demonstrated a high classification power and robustness with a classification accuracy of 89.16%. According to the simulation results, the developed adaptive identification model is with promising performance. The conclusions provide theoretical support for developing an adaptive strategy for connected eco‐driving.

Abstract Background Alzheimer's disease (AD) and other forms of dementia are the seventh leading cause of death. Studies discern the inclusion of air pollution among modifiable risk factors for dementia, while limited studies are for China. This study aims to examine the short-term association between airborne particulate matter (PM) and the hospitalizations of AD, including the economic costs in China. Methods A total of 4975 cases of AD patients hospitalized from 2017 to 2019, were collected from nine city and 411 medical institutions in Sichuan Province, China. Data on air pollutants such as PM2.5, PM10, and NO2 were obtained from 183 air quality monitoring stations in Sichuan Province. A time series-generalized additive model was used to estimate the association between short-term exposure to PM (lag1–lag7 and moving average lag01–lag07) and AD hospital admissions (HAs), stratified by gender, age, and season. Results Positive short-term exposure to airborne PM was found for the HAs of AD. The greatest effect on the number of AD inpatients was on single-day lag1 (PM2.5:1.034 (95% confidence interval (CI) 1.011, 1.058)). The association was also significant in the two-pollutant model. In the study period, 16.48% of AD HAs were attributed to the effect of PM. The total economic costs of AD attributable to PM exposure were US$ 2.56 million, including US$ 2.25 million of direct medical costs and US$ 0.31 million of indirect economic costs. Conclusions This study suggests that short-term exposure to airborne PM may increase the risk of AD HAs in Sichuan Province and result in associated economic costs.

Accurate and efficient landslide identification is an important basis for landslide disaster prevention and control. Due to the diversity of landslide features, vegetation occlusion, and the complexity of the surrounding surface environment in remote sensing images, deep learning models (such as U-Net) for landslide detection based only on optical remote sensing images will lead to false and missed detection. The detection accuracy is not high, and it is difficult to satisfy the demand. Synthetic aperture radar (SAR) has penetrability, and SAR images are highly sensitive to changes in surface morphology and structure. In this study, a multi-input channel U-Net landslide detection method fusing SAR, optical, and topographic multisource remote sensing data is proposed. First, a multi-input channel U-Net model fusing SAR multisource remote sensing data is constructed, then an attention mechanism is introduced into the multi-input channel U-Net to adjust the spatial weights of the feature maps of the multisource data to emphasize the landslide-related features, and finally, the proposed model is applied to the experimental scene for validation. The experimental results demonstrate that the proposed model combined with SAR multisource remote sensing data improves the perception ability of landslide features, focuses on learning landslide-related features, improves the accuracy of landslide detection, and reduces the rate of false detections and missed detections. Compared with the traditional U-Net landslide detection method based on SAR multisource remote sensing data and the traditional U-Net method that disregards SAR multisource remote sensing data, the proposed method has the best quantitative evaluation indicators. Among them, the proposed method obtained the highest F1 value (66.18%), indicating that fused SAR remote sensing data can provide rich and complementary landslide feature information, simultaneously setting up a multichannel U-Net model to input multisource remote sensing data can effectively process landslide feature information. The proposed method can provide theoretical and technical support for landslide disaster prevention and control.

Objective: Real-word data on long-acting luteinizing hormone-releasing hormone (LHRH) agonists in Chinese patients with prostate cancer are limited. This study aimed to determine the real-world effectiveness and safety of the LHRH agonist, goserelin, particularly the long-acting 10.8-mg depot formulation, and the follow-up patterns among Chinese prostate cancer patients. Methods: This was a multicenter, prospective, observational study in hormone treatment-naïve patients with localized or locally advanced prostate cancer who were prescribed goserelin 10.8-mg depot every 12 weeks or 3.6-mg depot every 4 weeks with or without an anti-androgen. The patients had follow-up evaluations for 26 weeks. The primary outcome was the effectiveness of goserelin in reducing serum testosterone and prostate-specific antigen (PSA) levels. The secondary outcomes included testosterone and PSA levels, attainment of chemical castration (serum testosterone

Abstract Background The promising therapeutic outcomes of neoadjuvant immunotherapy combined with chemotherapy in the treatment of locally advanced esophageal squamous cell carcinoma (ESCC) have been confirmed by several phase II clinical trials and have been widely demonstrated in clinical work. Theoretically, postoperative adjuvant immunotherapy may further improve the therapeutic effect, but there is still lack of evidence. The aim of this study was to analyse the safety and efficacy of perioperative immunotherapy (tislelizumab) in locally advanced resectable thoracic ESCC (PILOT trial). Methods Seventy-three eligible patients with pathologically confirmed thoracic ESCC of clinical T1b-3N1-3M0 or T3N0M0 stage were allocated to receive neoadjuvant immunotherapy (tislelizumab 200 mg d1, q3w × 2 cycles) plus chemotherapy (nad-paclitaxel 260 mg/m2 d1 + carboplatin AUC = 5 d1, q3w × 2 cycles) treatment. Patients with pathologic complete response (pCR) after esophagectomy received adjuvant tislelizumab (200 mg every 3 weeks for up to one year), and patients with non-pCR were assigned adjuvant tislelizumab plus chemotherapy for two cycles and then maintenance tislelizumab (200 mg every 3 weeks for up to 15 cycles). The primary endpoint of this study is 2-year disease-free survival (DFS) in non-pCR patients. The secondary endpoints include pCR rate, major pathological response rate, 2-year DFS in pCR patients, R0 resection rate, adverse events, and overall survival. Discussion This protocol was reviewed and approved by the Ethics Committee of Shanghai Chest Hospital (IS23059). This is the first prospective clinical trial to investigate the safety and efficacy of perioperative immunotherapy for locally advanced resectable thoracic ESCC. We hypothesize that perioperative immunotherapy could be a promising therapeutic strategy that can provide better 2-year DFS in non-pCR patients. Trial registration ClinicalTrial.gov: NCT0605633.