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Cardamine zhangjiajieensis, a new species from Hunan Province, China, is described and illustrated. Cardamine zhangjiajieensis is similar to C. circaeoides. From the latter, C. zhangjiajieensis is readily distinguished by the terminal leaflet of the cauline leaf 4.5–7 cm (vs. 2.5–4.5 cm), mostly round or oblong (vs. oblong-oval to triangular-oval), margin undulating sinuses (vs. crenate or subentire), seed apically narrow wing (vs. wingless).

Abstract Gastrointestinal stromal tumor (GISTs) are clinically heterogenous exhibiting varying degrees of disease aggressiveness in individual patients. We comprehensively describe the genomic and transcriptomic landscape of a cohort of 117 GISTs including 31 low-risk, 18 intermediate-risk, 29 high-risk, 34 metastatic and 5 neoadjuvant GISTs from 105 patients. GISTs have notably low tumor mutation burden but widespread copy number variations. Aggressive GISTs harbor remarkably more genomic aberrations than low-/intermediate-risk GISTs. Complex genomic alterations, chromothripsis and kataegis, occur selectively in aggressive GISTs. Despite the paucity of mutations, recurrent inactivating YLPM1 mutations are identified (10.3%, 7 of 68 patients), enriched in high-risk/metastatic GIST and functional study further demonstrates YLPM1 inactivation promotes GIST proliferation, growth and oxidative phosphorylation. Spatially and temporally separated GISTs from individual patients demonstrate complex tumor heterogeneity in metastatic GISTs. Finally, four prominent subtypes are proposed with different genomic features, expression profiles, immune characteristics, clinical characteristics and subtype-specific treatment strategies. This large-scale analysis depicts the landscape and provides further insights into GIST pathogenesis and precise treatment.

Abstract Grain hardness has important effects on grain quality and the end-use of wheat. In this study, a collection of 103 common wheat germplasms and a DH population of 194 lines were used to identify new quantitative trait loci (QTL) for grain hardness. Two stable genetic loci on chromosome 5D were detected under different locations and years with one of them being the Ha locus on 5DS where the major gene Puroindolines for wheat grain hardness is located. Another locus of qTaHa-5DL also showed a significant impact on grain hardness index (HI) with HI increasing from ~ 20 to ~ 45 and hardness type changing from soft to mixed when Puroindolines are wild type. A kompetitive allele-specific PCR (KASP) marker for qTaHa-5DL was developed and the effectiveness of the QTL was confirmed in 184 breeding lines with the marker K-Ha5DL dividing wheat into two distinct categories. This new QTL can be effectively used to select soft or medium hard wheat.

Abstract Intrahepatic circulation is essential for the repair of acute liver injury (ALI); however, very limited information is available concerning changes in the circulatory pathways during ALI. Therefore, multi-scale X-ray phase-contrast CT combined with three-dimensional (3D) visualization is used to quantitatively analyze the intrahepatic circulation pathway (including the hepatic vein, portal vein and hepatic sinusoid) in the mouse model via the intraperitoneal injection of carbon tetrachloride (CCl4) from acute injury to recovery. The results demonstrate that the liver still preserves some vessel-like channels accessed to the central vein when the injury causes the severe collapse of the hepatic sinusoids that cannot be observed in two-dimensional pathologic slices. Moreover, angiogenesis is observed in the terminal branches of the hepatic vein and portal vein. Additionally, we extend the two-dimensional primary lobule to a 3D model and find that the sinusoids in zone III have the most severe injury. The sinusoids in different zones also show changes in parameters such as density and mean diameter during the ALI. In conclusion, phase-contrast CT can reveal the intact vascular system within the liver lobes, thus providing critical information for studying the mechanisms involved in the evolution of circulatory structures from damage to repair.

BackgroundOral exposure to metals/metalloid elements in drinking water may be harmful to human health.ObjectiveTo assess potential health risks of oral exposure to 9 metals/metalloids in drinking water in Zibo City of Shandong Province from 2019 to 2023, and provide reference for the development of local drinking water management policies.MethodFrom 2019 to 2023, a total of 1178 drinking water samples were collected from 261 rural water monitoring sites and 14 urban water monitoring sites in 8 districts and counties of Zibo City. The US Environmental Protection Agency's (EPA) four-step health assessment model was used to evaluate the health risks of oral exposure to 9 metals/metalloids in drinking water for adults.ResultsA total of 1178 water samples were collected, including 561 urban water samples and 617 rural water samples; 769 samples of tap water and 409 samples of finished water; 634 samples collected in wet season and 544 in dry season. The median carcinogenic risk (CR) of arsenic exposure in drinking water for adults was 3.53×10−5, and the median hazard quotient (HQ) was 7.85×10−2. The HQs of arsenic and zinc showed an upward trend in recent years, while the HQ of aluminum showed a downward trend. The stratified analysis results showed that there was no statistically significant difference in the CR of arsenic between males and females or between urban water and rural water. The CR of arsenic in dry season was higher than that in wet season, and the CR of arsenic in tap water was higher than that in finished water (P

Abstract Extracellular adenosine is extensively involved in regulating the tumor microenvironment. Given the disappointing results of adenosine-targeted therapy trials, personalized treatment might be necessary, tailored to the microenvironment status of individual patients. Here, we introduce the adenosine signaling score (ADO-score) model using non-negative matrix fraction identified patient subtypes using publicly available melanoma dataset, which aimed to profile adenosine signaling-related genes and construct a model to predict prognosis. We analyzed 580 malignant melanoma samples and demonstrated its robust value for prognosis. Further investigation in immune checkpoint inhibitor dataset suggests its potential as a stratified factor of immune checkpoint inhibitor efficacy. We validated the power of the ADO-score at the protein level immunofluorescence in a melanoma cohort from Xiangya Hospital. More importantly, single-cell and spatial transcriptomic data highlighted the cell-specific expression patterns of adenosine signaling-related genes and the existence of adenosine signaling-mediated crosstalk between tumor cells and immune cells in melanoma. Our study reveals a robust connection between adenosine signaling and clinical benefits in melanoma patients and proposes a universally applicable adenosine signaling model, the ADO-score, in gene expression profiles and histological sections. This model enables us to more precisely and conveniently select patients who are likely to benefit from immunotherapy.

Abstract Purpose To investigate the role of Actin like 6 A (ACTL6A) in cancer and explore the potential mechanism of its function. Methods Differential expression of ACTL6A was analyzed using Oncomine and TIMER database. Then, we downloaded data sets from TCGA database. The correlation between ACTL6A expression and survival in pan-cancer were analyzed by “survival”, “survminer” R package and PrognoScan database. STRING (v 11.0) and stringAPP for Cytoscape v3.7.2 were used to predict ACTL6A associated genes. Copy number and methylation alterations of ACTL6A were analyzed using cBioPortal and GSCALite. Transcription factors were downloaded from The Human Transcription Factors Database and analyzed using “limma” R package, JASPAR and PROMO database. Correlations analysis between ACTL6A and immune cells were performed using TIMER and GEPIA database. Results In our studies, we found that ACTL6A was widely upregulated in cancers, which might be attributed to its gene amplifications. Moreover, ACTL6A might regulated by transcription factors (TFs), including E2F1, YY1, CDX2 and HOXD10. In addition, high ACTL6A expression was associated with poor prognosis in most cancers. Meanwhile, ACTL6A was associated with the infiltration of immune cells, especially in liver hepatocellular carcinoma and brain lower grade glioma. Conclusion Amplification of ACTL6A is correlated with poor prognosis and contribute to immune cells infiltration in LIHC and LGG, which may provide immune-related therapeutic targets to guide clinical strategies.

Abstract Background Ferroptosis is a type of regulated necrosis and glutathione peroxidase 4 (GPX4) has been recognized as a key enzyme that protects against ferroptosis. However, the significance of GPX4 in polymorphonuclear neutrophils (PMNs) of systemic lupus erythematosus (SLE) has not been explored. So we examined GPX4 mRNA in PMNs and analyzed its association with serological and clinical features. Methods A single center research from the Department of Rheumatology and Immunology of the Third Affiliated Hospital, Southern Medical University was conducted between December 2020 and September 2022. Real‐time transcription‐polymerase chain reaction analysis was used to determine the expression of GPX4 mRNA in PMNs from patients suffering from different rheumatoid immune diseases and healthy controls. The associations of GPX4 RNA levels in SLE patients with serological and clinical indicators were assessed by Spearman's correlation analysis. Receiver operating characteristic curve analysis was performed to evaluate the diagnostic value of GXP4 mRNA for SLE. Results GPX4 mRNA levels were lower in SLE patients than those in healthy individuals, patients with rheumatoid arthritis and axial spondyloarthritis. GPX4 mRNA levels were negatively correlated with the number of positive autoantibodies (r = −0.3072, p = 0.0300), anti‐dsDNA antibody (r = −0.3654, p = 0.0336), antinucleosome antibody (r = −0.4052, p = 0.0263), erythrocyte sedimentation rate (r = −0.3773, p = 0.0069), C‐reactive protein (r = −0.4037, p = 0.0036), and SLE disease activity index (r = −0.3072, p = 0.0300). GPX4 mRNA levels were downregulated in patients with alopecia compared with patients without alopecia (p

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.

Purpose – The purpose of this review is to comprehensively consider the material properties and processing of additive titanium alloy and provide a new perspective for the robotic grinding and polishing of additive titanium alloy blades to ensure the surface integrity and machining accuracy of the blades. Design/methodology/approach – At present, robot grinding and polishing are mainstream processing methods in blade automatic processing. This review systematically summarizes the processing characteristics and processing methods of additive manufacturing (AM) titanium alloy blades. On the one hand, the unique manufacturing process and thermal effect of AM have created the unique processing characteristics of additive titanium alloy blades. On the other hand, the robot grinding and polishing process needs to incorporate the material removal model into the traditional processing flow according to the processing characteristics of the additive titanium alloy. Findings – Robot belt grinding can solve the processing problem of additive titanium alloy blades. The complex surface of the blade generates a robot grinding trajectory through trajectory planning. The trajectory planning of the robot profoundly affects the machining accuracy and surface quality of the blade. Subsequent research is needed to solve the problems of high machining accuracy of blade profiles, complex surface material removal models and uneven distribution of blade machining allowance. In the process parameters of the robot, the grinding parameters, trajectory planning and error compensation affect the surface quality of the blade through the material removal method, grinding force and grinding temperature. The machining accuracy of the blade surface is affected by robot vibration and stiffness. Originality/value – This review systematically summarizes the processing characteristics and processing methods of aviation titanium alloy blades manufactured by AM. Combined with the material properties of additive titanium alloy, it provides a new idea for robot grinding and polishing of aviation titanium alloy blades manufactured by AM.

Abstract Bronchopulmonary dysplasia (BPD) is the most common sequela of prematurity and is characterized by alveolar simplification and lung angiogenesis failure. The aim of this study was to explore the immune signatures of BPD. Differentially expressed gene analysis and immune infiltration analysis were conducted to identify key immune cell types and related genes by using the mRNA-seq dataset GSE25286. The expression patterns of key genes were validated in the scRNA-seq dataset GSE209664 and in experiments. The cell–cell crosstalk of key immune cells was explored with CellChat. We found that differentially expressed genes between BPD mice and controls were mostly enriched in leukocyte migration and M1 macrophages were highly enriched in BPD lungs. Hub genes (Cybb, Papss2, F7 and Fpr2) were validated at the single-cell level, among which the downregulation of Cybb was most closely related to macrophage infiltration. The reduced mRNA and protein levels of Cybb were further validated in animal experiments. Colocalization analysis of Cybb and macrophage markers demonstrated a significant decrease of Cybb in M1 macrophages. Cell–cell crosstalk found that alveolar epithelial cells interacted actively with macrophages through MIF-(CD74 + CD44) signalling. In conclusion, M1 macrophages played important roles in promoting BPD-like lung injury, which was correlated with a specific reduction of Cybb in macrophages and the potential activation of MIF signalling.

Convolutional neural network (CNN) models are widely used in landslide susceptibility assessment due to their powerful feature extraction capabilities, and traditional CNN is no longer able to meet the requirements. Therefore, this paper proposes a multi-scale convolutional neural networks (MSCNN) model that can take into account deep and shallow features. By increasing the depth of the model and expanding the receptive field of samples, the MSCNN can tap deeper and more stable features to improve the reliability of landslide susceptibility assessment in complex scenarios. In this study, Shenzhen City is selected as the research area, and 12 landslide conditioning factors of landslides in Shenzhen City were selected based on systematic and representative principles. A multi-scale convolutional neural network landslide susceptibility assessment model is constructed and compared with methods such as multilayer perceptron (MLP), support vector machine (SVM), and random forest (RF). The results show that the AUC value (0.99) of the MSCNN model constructed in this paper is higher than that of MLP (0.97), SVM (0.91), and RF (0.85), which proves that the proposed MSCNN model has excellent prediction ability. The area of extremely high susceptibility in Shenzhen City is approximately 105.3 km², accounting for 4.98% of the total area of the study area, mainly distributed in Longgang District with steep slopes, sparse vegetation cover, and frequent human engineering activities. Slope, surface roughness, and surface relief are identified as the main conditioning factors affecting landslides in Shenzhen City. The landslide susceptibility mapping implemented in this paper reflects the current distribution of landslide disasters in Shenzhen City, providing data support and key technical support for future landslide disaster prevention and control in Shenzhen City.

Abstract The optimal timing and type of hematopoietic stem cell transplantation (HSCT) for treating peripheral T-cell lymphoma (PTCL) remain controversial. This retrospective real-world study investigated the application pattern and outcomes of HSCT in China. The analysis encompassed 408 PTCL patients with a median age of 45.5 years, all of whom received initial adequate therapy at five hospitals. Among patients with nodal PTCL who responded effectively to first-line therapy (the “responders”, n = 127) and subsequently underwent HSCT consolidation (n = 47, 37.0%), 93.6% received auto-HSCT, while 6.4% underwent allo-HSCT. Front-line auto-HSCT showed potential for long-term disease control in nodal PTCL responders. Among non-nodal PTCL responders (n = 80) with HSCT (n = 26, 32.5%), 46.2% underwent allo-HSCT and 53.8% received auto-HSCT. Upfront allo-HSCT provides longer progression-free survival (PFS) for non-nodal PTCL responders, with lower 3-year cumulative incidence of relapse (CIR) (16.7% vs. 56.0%) and comparable non-relapse mortality (NRM) (10.4% vs. 11.0%) compared to auto-HSCT. For patients who achieved remission with second-line salvage regimens, allo-HSCT was the primary choice (82.4%) for non-nodal PTCL, while auto-HSCT was more common (82.4%) in nodal PTCL. Nodal PTCL patients underwent auto-HSCT after ≥ 3 lines of treatment had a higher 3-year CIR (81.0%) compared to those treated in the first (26.0%) or second line (26.0%). Non-nodal PTCL patients underwent allo-HSCT after ≥ 3 lines had a higher 3-year NRM (37.5%) compared to after first (10.4%) or second line treatment (8.5%). These findings highlight distinct HSCT application patterns for PTCL in China, emphasizing the impact of early disease control and upfront consolidative HSCT.

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.

Conventional microscopes designed for submicron resolution in biological research are hindered by a limited field of view, typically around 1 mm. This restriction poses a challenge when attempting to simultaneously analyze various parts of a sample, such as different brain areas. In addition, conventional objective lenses struggle to perform consistently across the required range of wavelengths for brain imaging in vivo. Here we present a novel mesoscopic objective lens with an impressive field of view of 8 mm, a numerical aperture of 0.5, and a working wavelength range from 400 to 1000 nm. We achieved a resolution of 0.74 μm in fluorescent beads imaging. The versatility of this lens was further demonstrated through high-quality images of mouse brain and kidney sections in a wide-field imaging system, a confocal laser scanning system, and a two-photon imaging system. This mesoscopic objective lens holds immense promise for advancing multi-wavelength imaging of large fields of view at high resolution.

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

The parafoveal area, with its high concentration of photoreceptors and fine retinal capillaries, is crucial for central vision and often exhibits early signs of pathological changes. The current adaptive optics scanning laser ophthalmoscope (AOSLO) provides an excellent tool to acquire accurate and detailed information about the parafoveal area with cellular resolution. However, limited by the scanning speed of two-dimensional scanning, the field of view (FOV) in the AOSLO system was usually less than or equal to 2∘, and the stitching for the parafoveal area required dozens of images, which was time-consuming and laborious. Unfortunately, almost half of patients are unable to obtain stitched images because of their poor fixation. To solve this problem, we integrate AO technology with the line-scan imaging method to build an adaptive optics line scanning ophthalmoscope (AOLSO) system with a larger FOV. In the AOLSO, afocal spherical mirrors in pairs are nonplanar arranged and the distance and angle between optical elements are optimized to minimize the aberrations, two cylinder lenses are orthogonally placed before the imaging sensor to stretch the point spread function (PSF) for sufficiently digitizing light energy. Captured human retinal images show the whole parafoveal area with [Formula: see text] FOV, 60[Formula: see text]Hz frame rate and cellular resolutions. Take advantage of the 5∘ FOV of the AOLSO, only 9 frames of the retina are captured with several minutes to stitch a montage image with an FOV of [Formula: see text], in which photoreceptor counting is performed within approximately 5∘ eccentricity. The AOLSO system not only provides cellular resolution but also has the capability to capture the parafoveal region in a single frame, which offers great potential for noninvasive studying of the parafoveal area.

Objective To investigate the efficacy of erector spinal plane block (ESPB) after spinal fusion surgery in this study. Methods The PubMed, Embase, Cochrane library, and Web of Science databases were searched with a search deadline of March 30, 2024, and Stata 15.0 was used to analyze the data from the included studies. Result Nine randomized controlled trials involving 663 patients were included. Meta-analysis showed that EPSB could reduce pain scores at 2h (standard mean difference (SMD) = −0.78, 95% CI [−1.38 to −0.19], GRADE: Moderate), 6 h (SMD = −0.81, 95% CI [−1.23 to −0.38], GRADE: Moderate), 12 h (SMD = −0.59, 95% CI [−1.05 to −0.13], GRADE: Moderate), 24 h (SMD = −0.54, 95% CI [−0.86 to −0.21], GRADE: Moderate), 48 h (SMD = −0.40, 95% CI [−0.75 to −0.05], GRADE: Moderate) after spinal fusion surgery, as well as the PCA (analgesia medication use) (SMD = −1.67, 95% CI [−2.67 to −0.67], GRADE: Moderate). However, EPSB had no effect on intraoperative blood loss (SMD = −0.28, 95% CI [−1.03 to 0.47], GRADE: Low) and length of hospital stay (SMD = −0.27, 95% CI [−0.60–0.06], GRADE: Low). Conclusion Combined with the current findings, EPSB may reduce pain scores in spinal fusion surgery, possibly reducing the use of postoperative analgesics. However, due to the limitations of the study, we need more high-quality, multi-center, large sample randomized controlled trials to merge.

BackgroundCardiometabolic multimorbidity (CMM) and aging are increasing public health concerns. This prospective study used UK Biobank cohort to investigate the relationship between biological aging and the trajectory of CMM to dementia and mortality.MethodsCMM is the coexistence of at least two cardiometabolic diseases (CMD), including stroke, ischemic heart disease, and diabetes. Biological age was calculated using the KDM-BA and PhenoAge algorithms. Accelerated aging indicated biological age advances more rapidly than chronological age.ResultsThe study included 415,147 individuals with an average age of 56.5 years. During the average 11-year follow-up period, CMD-free individuals with accelerated aging had a significantly greater risk of CMD (KDM-BA, HR 1.456; PhenoAge, HR 1.404), CMM (KDM-BA, HR 1.952; PhenoAge, HR 1.738), dementia (KDM-BA, HR 1.243; PhenoAge, HR 1.212), and mortality (KDM-BA, HR 1.821; PhenoAge, HR 2.047) in fully-adjusted Cox regression models (p

The identification and quantification of xanthine are crucial for assessing the freshness and quality of food products, particularly in the seafood industry. Herein, a new approach was developed, involving the in-situ controllable growth of Pt91Ru9 nanoparticles on graphitic carbon nitride to yield Pt91Ru9@C3N4 catalytic materials. By integrating Pt91Ru9@C3N4 with the xanthine/xanthine oxidase (XOD) enzyme catalytic system, a nanozyme-enzyme tandem platform was obtained for the quantification analysis of xanthine. Under the catalytic oxidation of xanthine by XOD in the presence O2, H2O2 was generated. Upon the addition of peroxidase-like activity of Pt91Ru9@C3N4, H2O2 can be decomposed into •OH and 1O2, which can further catalyze the oxidation of TMB to its oxidation product oxTMB with an absorption peak at 652 nm. This smartphone-assisted portable colorimetric sensor for visual monitoring xanthine with a low detection limit of 8.92 nmol L−1, and successfully applied to detect xanthine in grass carp and serum samples.

IntroductionCurrently, no study has determined whether platelet transfusion refractoriness (PTR) post-hematopoietic stem cell transplantation (HSCT) before engraftment in patients with myelodysplastic syndrome (MDS) would impacts clinical outcomes.MethodsWe performed a MDS-specific retrospective analysis to determine whether PTR in one-month post-HSCT in patients with MDS could influence outcomes.Results and discussionAmong the 315 patients enrolled, 110 (34.9 %) had PTR from stem cell infusion to one-month post-HSCT. Baseline characteristics of the PTR and non-PTR groups were similar. We found that patients with PTR had a slower and lower rate of platelet engraftment by day 28, as well as a slower recovery of neutrophils. The median days of neutrophil and platelet engraftment were 14 days (9-23) and 17 days (8-28) in the PTR groups versus 13 days (9-23) and 15 days (7-28) in the non-PTR group (P1041ng/ml (median level) were independent adverse factors of platelet engraftment.

There is a certain failure rate in traditional glaucoma surgery because of the lack of depth information in microscope images. In this work, we present a digital microscope-integrated optical coherence tomography (MIOCT) system and several custom-made OCT-compatible instruments for glaucoma surgery. Sixteen ophthalmologists were asked to perform trabeculectomy and canaloplasty on live porcine eyes using the system and instruments. After surgery, a subjective feedback survey about the user experience was taken. The experiment results showed that our system can help surgeons easily locate important tissue structures during surgery. The custom-made instruments also solved the shadowing problem in OCT imaging. Surgeons preferred to use the system in their future practice.

Background: Since cardiovascular disease (CVD) stands as the primary cause of death in those with diabetes, and given the substantial influence of obesity as a common risk factor for both diabetes and atherosclerotic conditions, this investigation sought to find the relationship between anthropometric indicators and CVD risk within these populations. Methods: Our study examined 36,329 adults, including those with diagnosed diabetes, pre-diabetes, and without diabetes from National Health and Nutrition Examination Survey (NHANES) data spanning 1999 to 2018. Various anthropometric indicators such as body mass index (BMI), waist circumference, weight-adjusted waist index (WWI), waist-to-height ratio (WHtR), weight, and height were assessed. Baseline characteristics were compared among the three groups after weighting. Participants were then grouped based on anthropometric indicators, and logistic regression models were used to analyze the association between these indicators and CVD risk in the total diabetes group (including diabetic and pre-diabetic individuals). Threshold effect analysis was conducted to explore nonlinear relationships, and mediation analyses assessed whether serum parameters influenced these relationships. Results: This cross-sectional study involved 36,329 participants, weighted to a count of approximately 160.9 million, including over 45.9 million pre-diabetic individuals and around 16.6 million diabetic individuals. Baseline analysis showed significant associations between all six anthropometric indicators and CVD risk across patients with different diabetes statuses. Weighted restricted cubic spline (RCS) curve analysis highlighted increased CVD risk among the total diabetes group for each anthropometric indicator compared to the non-diabetic group. Anthropometric indicators were then divided into quartiles, and after adjusting for confounders, Model 3 revealed that the highest BMI group had a heightened risk of CVD compared to the lowest BMI group. Similar trends were observed in the WWI and WHtR subgroups. Threshold effect analysis of anthropometric indicators unveiled nonlinear associations between waist circumference, height, WWI and CVD risk. Mediation analysis suggested that lipid parameters, especially HDL, significantly mediated these relationships. Conclusion: In individuals with diabetes and pre-diabetes, BMI, weight, and WHtR displayed a consistent, linear increase correlation with CVD risk. Conversely, the link between waist circumference, height, and WWI and CVD risk showcased a more complex, nonlinear pattern. Moreover, HDL level emerged as notable mediator in the association between anthropometric indicators and the risk of CVD.

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.

Acetaminophen (APAP) overdose is a leading cause of drug-induced liver injury (DILI), with gender-specific differences in susceptibility. However, the mechanism underlying this phenomenon remains unclear. Our study reveals that the gender-specific differences in susceptibility to APAP-induced hepatotoxicity are due to differences in the gut microbiota. Through microbial multi-omics and cultivation, we observed increased gut microbiota-derived deguelin content in both women and female mice. Administration of deguelin was capable of alleviating hepatotoxicity in APAP-treated male mice, and this protective effect was associated with the inhibition of hepatocyte oxidative stress. Mechanistically, deguelin reduced the expression of thyrotropin receptor (TSHR) in hepatocytes with APAP treatment through direct interaction. Pharmacologic suppression of TSHR expression using ML224 significantly increased hepatic glutathione (GSH) in APAP-treated male mice. These findings suggest that gut microbiota-derived deguelin plays a crucial role in reducing APAP-induced hepatotoxicity in female mice, offering new insights into therapeutic strategies for DILI.

Non-landslide samples influence the outcomes of landslide susceptibility assessment. Existing studies did not fully consider the equilibrium between landslide and non-landslide samples in similar environments, resulting in poor reliability of landslide susceptibility assessment. This study proposed a non-landslide samples optimization method with a constraint of disaster-pregnant environment similarity to construct the balanced landslide and non-landslide samples. We employed the heterogeneous stacking and blending ensemble learning models to generate the landslide susceptibility assessment. This study focused on the Bailong River Basin with complex environment and frequent landslides as the study area. First, we extracted 12 landslide influencing factors based on multiple sources and analyzed the spatial distribution patterns of landslides. Second, we constructed similar environments based on the assessment units obtained from the curvature watershed method and selected an equal amount of both landslide and non-landslide samples in every different environment. Finally, three classic neural network models, namely multilayer perceptron, convolutional neural network, and gated recurrent unit were used as base models for stacking and blending ensemble learning models to assess landslide susceptibility. The findings suggested that the landslide susceptibility assessment results with optimized non-landslide samples were more reliable, especially the proposed method improved the prediction results in sample-sparse regions. The stacking ensemble constructed in this study demonstrated the highest area under the curve of 0.88 for the testing dataset, outperforming the blending ensemble and three base models. The issue of unreliable landslide susceptibility assessment results in sample-sparse regions within complex environments can be effectively addressed by considering the balanced sampling of non-landslide samples under the constraint of similar environments.

This study investigates the effects of glacial lakes on the flow velocities of Duiya Glacier, southern Tibetan Plateau, by employing satellite Synthetic Aperture Radar (SAR) Pixel-Offset-Tracking Small-Baseline-Subset (PO-SBAS) technology. Duiya Glacier, which terminates in a lake, exhibits approximately 10 m/yr higher horizontal speed and a higher melting rate with a vertical Non-Surface-Parallel-Flow (nSPF) velocity of – 7 m/yr than those of its land-terminating counterpart – West Duosangpu Glacier. Notably, Duiya Glacier experiences significant seasonal velocity fluctuations with accelerated flow between May and October. By integrating glacier geometry, changes in glacier boundaries and the extent of proglacial lakes, the distribution of supraglacial lakes, and climatic variables, we reveal that proglacial and supraglacial lakes play a crucial role in increasing the flow velocities of Duiya Glacier. Duiya Glacier flows faster because of increased subglacial water pressure resulting from water influx from these lakes. This phenomenon becomes conspicuously evident during May – October, when increased meltwater due to increased temperatures and precipitation further elevates the subglacial water pressure. Our method highlights the potential for understanding the impact of glacial lakes on glacier movements at a large scale, leveraging the capabilities of satellite SAR PO-SBAS technology for continuous, wide-scale, high temporal resolution, and 3D velocity monitoring.

AbstractObjective: To evaluate the efficacy and feasibility of ultrasound-guided percutaneous thermal ablation (TA) for treating benign parotid tumors.Methods: Patients with benign parotid tumors who underwent ultrasound-guided microwave ablation (MWA) or radiofrequency ablation (RFA) between January 2020 and March 2023 were included in this retrospective study. Change in tumor size (maximum diameter, tumor volume(V), volume reduction rate (VRR)) and cosmetic score (CS) were evaluated during a one-year follow-up period. We also recorded the incidence of any complications associated with TA.Results: A total of 23 patients (13 males and 10 females; median age 65 years, range 5–91 years) were included. The mean VRR at 1, 3, 6, and 12 months after TA was 37.03%±10.23%, 56.52%±8.76%, 82.28%±7.89%, and 89.39%±6.45%, respectively. Mean CS also changed from 3.39 ± 0.66 to 1.75 ± 0.93 (p

ABSTRACTWe develop an integrated neural network landslide susceptibility assessment (LSA) method that integrates temporal dynamic features of interferometry synthetic aperture radar (InSAR) deformation data and the spatial features of landslide influencing factors. We construct a time-distributed convolutional neural network (TD-CNN) and bidirectional gated recurrent unit (Bi-GRU) to better understand the temporal dynamic features of InSAR cumulative deformation, and construct a multi-scale convolutional neural network (MSCNN) to determine the spatial features of landslide influencing factors, and construct a parallel unified deep learning network model to fuse these temporal and spatial features for LSA. Compared with the traditional MSCNN method, the accuracy of the proposed model is improved by 1.20%. The performance of the proposed model is preferable to MSCNN. The area under the receiver operating characteristic curve (AUC) of the testing set reaches 0.91. Our LSA results show that the proposed model clearly depicts areas with very high susceptibility landslides. Further, only 10.18% of the study area accurately covers 84.79% of historical landslide areas. Subjective consequences and objective indicators show that the proposed model that is integrated time-series InSAR deformation dynamic features can make full use of landslide characteristics and effectively improve the reliability of LSA.

ObjectiveThe aim of this study was to investigate the genotypic and clinical phenotypic characteristics of MAX germline mutation–associated pheochromocytoma (PCC) and paraganglioma (PGL).MethodsWe retrospectively analyzed the family investigation data and clinical genetic characteristics of six individuals from three independent families with PCC carrying MAX germline mutations from December 2005 to March 2024. A literature review was then conducted of the six carriers and another 103 carriers from the other 84 families with MAX germline mutations reported previously.ResultsThere were 109 patients in 87 families with all five exons and 53 types of MAX germline mutations. p.R33* (c.97C>T; 21.1%), p.R75* (c.223C>T; 13.8%), and p.A67D (c.200C>A; 7.3%), which accounted for 42.2% of mutations detected, were the most common mutations. Moreover, 101 (92.7%) patients developed PCCs, including 59 bilateral PCCs and 42 unilateral PCCs, and 19 (18.8%) patients showed metastasis. The mean age at diagnosis was 32.8 ± 12.6 (13-80) years. The male-to-female ratio was 1.3:1. In 11 (10.9%) patients, the PCC was accompanied by chest or abdominal PGL, and one other patient had sole head and neck PGL. Nine (8.3%) patients also had functional pituitary adenomas, 11 (10.9%) developed other neuroendocrine tumors (NETs), and 7 (6.4%) presented with concomitant non-NET. Meanwhile, MAX-p.Q82Tfs*89 and p.E158A mutations are reported for the first time in this study.ConclusionMAX germline mutations may cause new types of multiple endocrine neoplasia. A comprehensive baseline assessment of neural crest cell–derived diseases is recommended for all individuals with MAX germline mutations. The risk of bilateral and metastatic PCCs should also be considered.

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