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Abstract Background Atrial natriuretic peptide (ANP) has been associated with ischemic stroke (IS), but the underlying molecular mechanisms are not clear. The objective of this study was to examine whether DNA methylation and hydroxymethylation in the coding gene of ANP (NPPA) were associated with IS, as well as its functional outcome. Methods and results DNA methylation and hydroxymethylation in NPPA promoter region were quantified by targeted bisulfite sequencing and APOBEC-coupled epigenetic sequencing, respectively, in 615 IS patients and 610 age- and sex-matched healthy controls. True methylation was calculated as the quantified methylation level minus the quantified hydroxymethylation level. The functional outcome of IS was evaluated by the modified Rankin Scale (mRS) at a 3-month follow-up visit after onset. Multiple testing was controlled by the false discovery rate approach. Of the nine CpG sites assayed, hypomethylation at eight CpGs was not only associated with an increased risk of having IS but also predicted a higher mRS score after onset (all q

Purpose: Erectile dysfunction (ED) is associated with several vascular disorders, but the associations between ED and vascular parameters are still unclear. Materials and Methods: We analyzed and synthesized a comprehensive range of studies from PubMed, Web of Science, and Scopus regarding the associations between ED and the following measures: ankle-brachial index (ABI), pulse wave velocity (PWV), intima-media thickness (IMT), nitrate-mediated dilation (NMD), flow-mediated dilation (FMD), augmentation index (AI), endothelial progenitor cells (EPCs) and other vascular parameters. Subgroup analysis was conducted according to specific types of parameters. Study quality was assessed by using the Newcastle–Ottawa Scale. Sensitivity analysis was conducted to confirm the robustness of the pooled results. Results: Fifty-seven studies with 7,312 individuals were included. Twenty-eight studies were considered to be high-quality. ED patients had a 0.11 mm higher IMT (95% confidence interval [CI]: 0.07, 0.15), a 2.86% lower FMD (95% CI: -3.56, -2.17), a 2.34% lower NMD (95% CI: -3.37, -1.31), a 2.83% higher AI (95% CI: 0.02, 5.63), a 1.11 m/s higher PWV (95% CI: 0.01, 2.21), and a 0.72% lower percentage of EPCs (95% CI: -1.19, -0.24) compared to those without ED. However, ABI was similar between ED patients and non-ED individuals. According to sensitivity analysis, the pooled results were robust. Conclusions: Our study confirmed the associations between ED and several vascular parameters and highlighted the importance of prevention and management of vascular and endothelial dysfunction in ED patients.

Abstract Background Fluorine-18 fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) has some limitations in diagnosis of Intrahepatic cholangiocarcinoma (ICC). Materials and methods Patients with histologically confirmed ICC who underwent both [18F]FDG and 18F-labeled fibroblast-activation protein inhibitors ([18F]FAPI)-04 PET/CT were prospectively analyzed. The maximum standard uptake value (SUVmax), tumor-to-background ratio (TBR), metabolic tumor volume (MTV), total lesion glycolysis (TLG), [18F]FAPI–avid tumor volume (FTV), total lesion fibroblast activation protein expression (TLF) were compared between the two modalities by paired Wilcoxon signed-rank test and Mann–Whitney U test, and McNemar’s test was used to assess the diagnostic accuracy between the two techniques. Results In total, 23 patients with 389 lesions were included. Compared to [18F]FDG, [18F]F-FAPI-04 PET/CT demonstrated a higher detection rate for intrahepatic lesions (86.3% vs. 78.2% P = 0.040), lymph node metastases (85.2% vs. 68.2%, P = 0.007), peritoneal metastases (100% vs. 93.8%), and bone metastases (100% vs. 70.5%, P

Abstract Small-scale rock cutting tests serve as a simple approach to evaluate the performance of tunnel boring machines (TBMs), but the feasibility of this method requires further investigation. Herein, a small-scale rotary cutting machine is developed to conduct rock cutting tests, and the cutting performance is investigated. The results indicate that similar cutting performance can be achieved through both small-scale and full-scale tests. The critical penetration depth for effective rock cutting by the cutter is 0.5 mm, below which the cutter grinds against the rock. The optimal ratio of cutting spacing to penetration depth obtained in small-scale tests is 4.47. A result within the empirical range can be achieved by multiplying the optimal small-scale cutting parameters with the scale coefficient, demonstrating the feasibility of using small-scale tests to guide the design of cutter heads. Based on the test result, the scale prediction model is constructed to predict the full-scale cutting force. The predictive capability of the proposed model and CSM model is validated using 72 sets of full-scale test data involving the same types of rock, and the predictions of the proposed model are closer to the test data.

Objective To investigate the therapeutic effect of electroacupuncture at Lianquan point combined with transcranial direct current stimulation (tDCS) on elderly patients with swallowing disorder after stroke. Methods From July 2022 to November 2023, a total of 116 elderly patients with swallowing disorder after stroke admitted to Handan Central Hospital were divided into a control group and a study group according to random number table, each had 58 cases. The control group was treated with tDCS, and the a study group was treated with electroacupuncture at Lianquan point combined with tDCS. The total effective rate, swallowing difficulties ［modified Mann assessment of swallowing ability scale (MASA)］, nutritional indexes ［serum prealbumin (PA) and albumin (ALB)］, surface electromyography results (EMG swallowing duration and maximum amplitude), nerve injury indexes ［brain-derived neurotrophic factor (BDNF) and neuropeptide Y (NPY)］ and long-term prognostic indicators ［activities of daily living scale (ADL)］ were compared between the two groups. Results After treatment, the total effective rate and MASA score in the study group were higher than those in the control group; PA and ALB were higher than those in the control group, swallowing duration was shorter than that in the control group, and the maximum amplitude was larger than that in the control group. BDNF was higher than that in the control group, NPY was lower than that in the control group; the ADL score was higher than that in the control group, with statistical significance (P

Abstract Objective To compare the performance of [18F]FDG and [18F]FAPI-04 in PET/CT evaluation for liver cancer lesions, with a further exploration of the associations between PET semiquantitative data and immunohistochemical markers to liver cancer. Methods Patients with suspected malignant liver lesions (MLL) underwent [18F]FDG and [18F]FAPI-04 PET/CT scanning. Liver lesions were visually classified as positive or negative based on their uptake level exceeding that of adjacent normal liver tissue. SUVmax and tumor-to-background ratio (TBR) were recorded for semi-quantitative analysis. Sensitivity, specificity and accuracy of each tracer were determined using pathological findings as the gold standard. Furthermore, immunohistochemical analysis provided the molecular characteristics of all MLLs. Comprehensive analysis explored correlations between these molecular markers and PET semiquantitative parameters (SUVmax andTBR) to identify potential associations. Results The study enrolled 44 patients, with 39 confirmed cases of MLL, comprising 28 hepatocellular carcinomas (HCC) and 11 intrahepatic cholangiocarcinomas (ICC). For MLL detection, [18F]FAPI-04 and [18F]FDG exhibited sensitivities of 84.6% (33/39) and 76.9% (30/39), specificitiesy of 60% (3/5) and 100%(5/5), and accuracy of 81.8% (36/44) and 79.5%(35/44). Across all liver lesions, [18F]FAPI-04 significantly surpassed [18F]FDG in SUVmax(10.54 ± 6.72 VS. 7.68 ± 6.79) and TBR(4.35 ± 3.78 Vs. 3.17 ± 3.05). Notably, [18F]FAPI-04 displayed markebly elevated SUVmax in benign liver lesions (BLLs) (P = 0.032), HCCs (P = 0.005), and ICCs (P = 0.011). Lesions with hepatocyte negativity (P = 0.023), CD34 negativity(P = 0.044), and high Ki67 expression (> 30%) (P = 0.001) had higher SUVmax on [18F]FAPI-04. Additionally, ARG-1-negative lesions demonstrated higher TBR on [18F]FAPI-04 than ARG-1-positive lesions(P = 0.018). No significant SUVmax/TBR differences were observed with [18F]FDG based on these markers. A linear relationship was identified between Ki67 scores and SUVmax of [18F]FAPI-04 (R = 0.603, P

Abstract Background The gut microbiota may be involved in neuropathic pain. However, the causal association between gut microbiota and neuropathic pain remains unclear. Whether immune cells and inflammatory factors mediate the pathway from gut microbiota to neuropathic pain has not been elucidated. Methods We obtained the summary data of 412 gut microbiota, 731 immune cells, 91 inflammatory factors, and five types of neuropathic pain (drug-induced neuropathy, postherpetic neuralgia, sciatica, trigeminal neuralgia, and unspecified neuralgia) from large-scale genome-wide association study (GWAS) datasets and the FinnGen database. We used bidirectional Mendelian randomization (MR) analysis to explore the causal association between gut microbiota and neuropathic pain. Additionally, we conducted a mediation analysis to identify whether immune cells and inflammatory factors act as mediators within these causal relationships. Results Our study revealed 30 causal relationships between 26 gut bacterial taxa and five types of neuropathic pain, including four associated with drug-induced neuropathy, six with postherpetic neuralgia, five with sciatica, eight with trigeminal neuralgia, and seven with unspecified neuralgia. Moreover, we identified 35 gut bacterial pathway abundances causally involved in neuropathic pain. The reverse MR analysis showed no evidence of reverse causality from gut microbiota to neuropathic pain. Mediation analysis demonstrated that the immune cell phenotype “HLA-DR++ monocyte % leukocyte” mediated the causal relationship between p_Proteobacteria and sciatica with a mediation proportion of 36.15% (P = 0.038), whereas “CD11c on CD62L+ myeloid dendritic cell” mediated the causal pathway from assimilatory sulfate reduction to trigeminal neuralgia with a mediation proportion of 27.90% (P = 0.041). Conclusion This study identified the causal relationships between several specific gut microbiota and various neuropathic pain subtypes. Additionally, two immune cells may act as potential mediators in the pathways from gut microbiota to neuropathic pain.

Introduction: Combination immunotherapy holds promise for improving survival in responsive glioblastoma (GBM) patients. Programmed death-ligand 1 (PD-L1) expression in immune microenvironment (IME) is the most important predictive biomarker for immunotherapy. Due to the heterogeneous distribution of PD-L1, post-operative histopathology fails to accurately capture its expression in residual tumors, making intra-operative diagnosis crucial for GBM treatment strategies. However, the current methods for evaluating the expression of PD-L1 are still time-consuming. Objective: To overcome the PD-L1 heterogeneity and enable rapid, accurate, and label-free imaging of PD-L1 expression level in GBM IME at the tissue level. Methods: We proposed a novel intra-operative diagnostic method, Machine Learning Cascade (MLC)-based Raman histopathology, which uses a coordinate localization system (CLS), hierarchical clustering analysis (HCA), support vector machine (SVM), and similarity analysis (SA). This method enables visualization of PD-L1 expression in glioma cells, CD8+ T cells, macrophages, and normal cells in addition to the tumor/normal boundary. The study quantified PD-L1 expression levels using the tumor proportion, combined positive, and cellular composition scores (TPS, CPS, and CCS, respectively) based on Raman data. Furthermore, the association between Raman spectral features and biomolecules was examined biochemically. Results: The entire process from signal collection to visualization could be completed within 30 min. In an orthotopic glioma mouse model, the MLC-based Raman histopathology demonstrated a high average accuracy (0.990) for identifying different cells and exhibited strong concordance with multiplex immunofluorescence (84.31 %) and traditional pathologists' scoring (R2 ≥ 0.9). Moreover, the peak intensities at 837 and 874 cm−1 showed a positive linear correlation with PD-L1 expression level. Conclusions: This study introduced a new and extendable diagnostic method to achieve rapid and accurate visualization of PD-L1 expression in GBM IMB at the tissular level, leading to great potential in GBM intraoperative diagnosis for guiding surgery and post-operative immunotherapy.

The construction of the nanohybrid composed of two carbonaceous nanomaterials is a promising strategy to inhibit their aggregation, and effectively exert the advantages of their excellent mechanical properties as reinforcement for polymers. Here, carbon nanotubes (CNTs) were in situ perpendicularly growing on the surface of graphene oxide (GO) through metal-organic frameworks (MOF)-derived strategy by chemical vapor deposition (CVD), aiming to facilitate their dispersion on poly(l-lactic acid) (PLLA) bone scaffold fabricated by selective laser sintering (SLS). Specifically, GO provided nucleation sites for the growth of MOF, and worked as the templates when CNTs grew, in which MOF provided catalysts and carbon sources simultaneously. The precursor was heated to 550 °C and kept for 2 h, then heated to 900 °C and kept for 2 h before cooling. The obtained nanohybrid (GO@CNT) exhibited a superior dispersion state than the pure GO in the scaffold at the same loading, especially when the loading was 0.75 wt%. Adding 0.75 wt% GO@CNT endowed the scaffold with a remarkable increment in tensile strength and compressive strength of 13.36 MPa and 24.72 MPa with enhancement of 55.35% and 18.85%, respectively, compared to the scaffold containing 0.75 wt% GO. A crack extension model combined with experiment results was proposed to better understand reinforcement mechanisms. Additionally, the scaffold containing GO@CNT exhibited benign cytocompatibility with a cell-spreading area of 86.31% and cell density of 564 cells/mm2 after culturing for 5 d according to the results of cell adhesion and immunofluorescence tests, making it a promising candidate for bone defect repair.

ObjectivesWith the implementation of the national “Dual Carbon Strategy” (carbon peak and carbon neutrality), it is anticipated that the existing coating structures may not meet the requirements of future gas turbine thermal protection coatings. The concept of a new type of environmental/thermal barrier coating (E/TBC) structure with high temperature corrosion resistance has been proposed to meet the demand for thermal protection coatings in hybrid hydrogen combustion engines.MethodsThe development history and research status of thermal barrier coating (TBC), environmental barrier coating (EBC), thermal/environmental barrier coating (T/EBC) and thermal and environmental barrier coating (TEBC) were reviewed and analyzed from the perspective of thermal protection coating materials and coating structures. Moreover, the gap between the above coating structures and the requirementsof thermal protection coating for mixed hydrogen gas turbines was investigated.ResultsIt is reasonable to superimpose the function of EBC onto the thermal protection coating of current mixed hydrogen gas turbines, thereby forming a new type of E/TBC structure with high temperature corrosion resistance on the high-temperature alloy substrate.ConclusionsThrough the preliminary test, it is proved that the new E/TBC structure is suitable for the thermal protection coating requirements of mixed hydrogen gas turbine against high temperature water oxygen corrosion, and it is pointed out that the theory and application research of this new E/TBC thermal protection coating should be vigorously carried out.

Abstract Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic lung disease with limited treatment options and efficacy. Evidence suggests that IPF arises from genetic, environmental, and aging-related factors. The pathogenic mechanisms of IPF primarily involve dysregulated repeated microinjuries to epithelial cells, abnormal fibroblast/myofibroblast activation, and extracellular matrix (ECM) deposition, but thus far, the exact etiology remains unclear. Noncoding RNAs (ncRNAs) play regulatory roles in various biological processes and have been implicated in the pathophysiology of multiple fibrotic diseases, including IPF. This review summarizes the roles of ncRNAs in the pathogenesis of IPF and their potential as diagnostic and therapeutic targets.

Abstract Clinical studies and meta-analyses have suggested a link between thyroid dysfunction and lens opacification. The objective of this study is to investigate the causal relationship between hyperthyroidism and the development of cataracts using the Mendelian randomization approach, with the aim of filling the gap in knowledge about the systemic effects of hyperthyroidism on ocular health. Leveraging genetic variants as instrumental variables, the analysis used extensive datasets from the UK Biobank and the FinnGen Database and employed three common approaches for causal inference (the Inverse Variance Weighted method, a regression based method the Weighted Median estimator, and MR-Egger regression) and accompanying sensitivity analyses to ensure robustness. The results demonstrate that there is a strong likely causal relationship, with hyperthyroidism increasing the risk of developing senile cataracts (OR = 361.09, 95%CI 5.024 to 2.60 × 104, P = 0.007). A sensitivity analysis provided no evidence of horizontal pleiotropy and no significant outliers, suggesting the results are robust. In conclusion, our study established a significant causal relationship between hyperthyroidism and increased risk of cataract development, underscoring the importance of considering the systemic effects of hyperthyroidism in clinical and public health interventions and policies. Future research should focus on elucidating the molecular mechanisms underlying this association, exploring the potential benefits of early intervention in hyperthyroidism to prevent cataract development, and investigating whether these findings translate across different ethnic populations. Additionally, further GWAS studies aimed at identifying genetic variants associated with both hyperthyroidism and cataracts are warranted to confirm and expand upon our results.

Tongtong Xu,1,* Xiaojing Zhong,1,* Nana Luo,2,* Wenyi Ma,1 Pingsheng Hao2 1School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2Department of Dermatology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Pingsheng Hao, Email hpswl@126.comAbstract: In psoriasis, keratinocytes are triggered by factors, such as infection or tissue damage, to release DNA, which thereby activates plasmacytoid dendritic cells and macrophages to induce inflammation, thickened epidermis, and parakeratosis. The recognition of double‐stranded (ds)DNA facilitates the activation of cytoplasmic DNA sensors absent in melanoma 2 (AIM2) inflammasome assembly and cyclic guanosine monophosphate adenosine monophosphate (cGAMP) synthase (cGAS) - stimulator of interferon gene (STING) pathway, both of which play a pivotal role in mediating the inflammatory response and driving the progression of psoriasis. Additionally, secreted proinflammatory cytokines can stimulate further DNA release from keratinocytes. Notably, the activation of AIM2 and cGAS-STING signaling pathways also mediates programmed cell death, potentially enhancing DNA overproduction. As a result, excessive DNA can activate these pathways, amplifying persistent inflammatory responses that contribute to the maintenance of psoriasis. Several studies have validated that targeting DNA and its mediated activation of AIM2 and cGAS-STING offers promising therapeutic strategies for psoriasis. Here, we postulate a hypothesis that excessive cytosolic DNA can activate AIM2 and cGAS-STING, mediating inflammation and programmed cell death, ultimately fostering DNA accumulation and contributing to the development of psoriasis.Keywords: DNA, AIM2, cGAS, STING, psoriasis

Abstract This paper proposes a robust image encryption algorithm that utilizes a Novel three-dimensional (3D) Chaotic map and an Enhanced Logistic Sine System (ELSS). We leverage the unpredictability of 3D chaotic dynamics alongside the complexity of ELSS and DNA Sequence to forge a formidable image encryption scheme. Firstly, the image pixels are converted from decimal to hexadecimal notation and sorted in a 1D pixel array carrying a unique sequence of three channels of the RGB image. Secondly, the secret key is appended to XOR, the values with that 1-D pixels array. Thirdly, values are sorted by performing the binary right shift operation and encoded into DNA. Fourthly, a novel chaotic map is used to perform scrambling operations. Lastly, a novel enormous keyspace ELSS is used to perform efficient Border and Cross-Border (B &CB) pixel exchange, further enhancing the encryption quality of the proposed algorithm. Comprehensive security analysis proved that the proposed algorithm exhibits remarkable resilience against powerful known and chosen plaintext attacks and other prevalent cryptanalysis attacks, including differential attacks and exhaustive key search attacks. Henceforth, the proposed algorithm’s superior security and low computational cost make it an ideal choice for real-time secure image communication across various platforms, including satellite, multimedia, and military communications.

Qian Gao,1,2 Ping-Sheng Hao1 1Dermatology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2Department of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of ChinaCorrespondence: Ping-Sheng Hao, Email hpswl@126.comAbstract: The ability of the skin to “remember” has been a potential mechanism for studying recurrent skin diseases. While it has been thought that the ability to retain past encounters is the prerogative of immune cells, it has recently been discovered that skin tissue stem cells can also take on this task. Epithelial stem cells undergoing inflammation retain their “memory” through epigenetic reprogramming and exhibit rapid epithelialization and epidermal proliferation upon secondary stimulation. This is a non-specific memory modality independent of conventional immune memory, in which histone modifications (acetylation and methylation) and specific transcription factors (AP-1 and STAT3) are involved in the establishment of inflammatory memories, and AIM2/Caspase-1/IL-1β mainly performs the rapid effects of memory. This finding is intriguing for addressing recurrent inflammatory skin diseases, which may explain the fixed-site recurrence of inflammatory skin diseases and develop new therapeutic strategies in the future. However, more research is still needed to decipher the mysteries of memory.Keywords: inflammatory memory, recurrent inflammatory skin diseases, epigenetics, skin tissue stem cells

Abstract Data envelopment analysis (DEA) is a popular nonparametric tool for measuring the performance of decision making unit (DMU). Cross-efficiency evaluation is an efficient means to rank DMUs, which compensates for efficiency overestimation and incomplete ranking of conventional DEA models. With respect to incomplete rational cross-efficiency evaluation, the common methods construct models with two extreme efficiencies as reference, such as efficiency values of the aggressive and benevolent models. In addition, they only explore the irrational preferences of decision maker (DM) at a certain stage in the evaluation process. They fail to investigate the cross-efficiency evaluation synthetically under incomplete rationality and characterize the complexity of the individuals’ decision making. To fill this gap, a new method must be proposed. This paper proposes a new cross-efficiency termed regret cross-efficiency model using attitudinal entropy approach (RACE), which constructs a secondary goal model from a comprehensive perspective under the framework of regret theory, and introduces attitudinal entropy to aggregate the cross-efficiencies. Besides, this paper presents some empirical examples to illustrate the validity and robustness of the RACE method.

Abstract This study proposes a frequency coupling suppression strategy for voltage source converters (VSCs) with DC‐link dynamics to address the challenges posed by the asymmetric system structures for system modelling and control design. The strategy introduces a reshaping outer loop into the q‐axis, which eliminates the conjugate voltages and currents induced by the DC‐link dynamics, to achieve decoupling of the DC‐link voltage control (DVC). Therefore, the VSC is modelled as a single‐input single‐output (SISO) admittance model, which provides clear physical insights for the analysis of admittance characteristics. Compared with the admittance matrix, the SISO model reveals the dominance of each control dynamics on VSC admittance in different frequency bands. This insight facilitates the exploration of optimized control strategies to improve the system stability margin. Based on the SISO model, a virtual admittance for compensating the negative resistive effect of the PLL is designed to illustrate the advantages of the proposed method in providing design‐oriented analysis. Experimental results verify the effectiveness of the proposed control strategy.

Abstract Background Vascular health has been associated with cognition but related evidence is limited in Chinese. The objective of this study was to examine the association of vascular aging assessed by arterial stiffness and blood pressure with cognitive function in an unselected Chinese population. Methods In the Tianning Cohort (N = 5158), indicators of arterial stiffness and blood pressure including carotid-femoral pulse wave velocity (cfPWV), ankle-brachial index (ABI), pulse pressure (PP), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were measured. Cognitive function was assessed using the Mini Mental State Examination (MMSE) questionnaire. We applied Poisson regression and logistic regression to examine the associations of vascular aging and blood pressure with cognitive function. Results 76 (1.47%) participants had impaired cognitive function diagnosed by a MMSE score of less than 24 points. Participants with a higher level of PP were more likely to have a decreased score of MMSE (β=-0.0121, P

Prostate cancer (PCa) is a multifocal disease characterized by genomic and phenotypic heterogeneity within a single gland. In this study, Visium spatial transcriptomics (ST) analysis was applied to PCa tissues with different histological structures to infer the molecular events involved in Gleason score (GS) progression. The spots in tissue sections were classified into various groups using Principal Component Analysis (PCA) and Louvain clustering analysis based on transcriptome data. Anotation of the spots according to GS revealed notable similarities between transcriptomic profiles and histologically identifiable structures. The accuracy of macroscopic GS determination was bioinformatically verified through malignancy-related feature analysis, specifically inferred copy number variation (inferCNV), as well as developmental trajectory analyses, such as diffusion pseudotime (DPT) and partition-based graph abstraction (PAGA). Genes related to GS progression were identified from the differentially expressed genes (DEGs) through pairwise comparisons of groups along a GS gradient. The proteins encoded by the representative oncogenes UQCRB and LBH were found to be highly expressed in advanced-stage PCa tissues. Knockdown of their mRNAs significantly suppressed PCa cell proliferation and invasion. These findings were validated using The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA-PRAD) dataset, as well as through histological and cytological experiments. The results presented here establish a foundation for ST-based evaluation of GS progression and provide valuable insights into the GS progression-related genes UQCRB and LBH.

Cerebral cavernous malformation (CCM) is a polygenic disease with intricate genetic interactions contributing to quantitative pathogenesis across multiple factors. The principal pathogenic genes of CCM, specifically KRIT1, CCM2, and PDCD10, have been reported, accompanied by a growing wealth of genetic data related to mutations. Furthermore, numerous other molecules associated with CCM have been unearthed. However, tackling such massive volumes of unstructured data remains challenging until the advent of advanced large language models. In this study, we developed an automated analytical pipeline specialized in single nucleotide variants (SNVs) related biomedical text analysis called BRLM. To facilitate this, BioBERT was employed to vectorize the rich information of SNVs, while a deep residue network was used to discriminate the classes of the SNVs. BRLM was initially constructed on mutations from 12 different types of TCGA cancers, achieving an accuracy exceeding 99%. It was further examined for CCM mutations in familial sequencing data analysis, highlighting an upstream master regulator gene fibroblast growth factor 1 (FGF1). With multi-omics characterization and validation in biological function, FGF1 demonstrated to play a significant role in the development of CCMs, which proved the effectiveness of our model. The BRLM web server is available at http://1.117.230.196.

Abstract Double-layer island working face main roadway coal pillars are affected by complex mining stress superposition, when different coal pillar width combinations, the surrounding rock stress field will produce different degrees of regional loading increase effect; the study of the surrounding rock stress field regional superposition loading increase law is meaningful to explaining the failure mode of the roadway and determining the critical control area. This study combines numerical simulation with on-site monitoring and other methods and draws the following conclusions: The superimposed loading increase law (“decreasing” → “increasing”) of the abutment pressure and deviatoric stress in the lower coal seam of the double-layer island working face during the mining; the type of the principal stress deflection in the advance working face region; and by obtaining the three types of development morphology of the deviatoric stress peak zone of the roadway and its corresponding nine evolution modes (one type of circular tube → four types of inverse hyperbolic body → four types of hyperbolic body) in the double-layered island working face mining. Indicated the critical reinforcement area corresponding to the main roadway when at different combinations of coal pillar widths; determined the main track roadway protective coal pillars width for 40 m and the shape of the roadway peak deviatoric stress zone is the inverse class hyperbolic body mode; according to the evolution mode of the peak deviatoric stress zone, determined the synergistic failure control program for the asymmetric critical zone of the roadway surrounding rock which is a targeted scientific support method; after the feedback of on-site monitoring and, the support program is reasonable and effective.

Abstract Pseudorabies have caused enormous economic losses in China’s pig industry and have recurred on many large pig farms since late 2011. The disease is caused by highly pathogenic, antigenic variant pseudorabies virus (vPRV) strains. Our laboratory isolated a pseudorabies virus in 2015 and named it XJ5. The pathogenic ability of this mutant strain was much stronger than that of the original isolate. After we sequenced its whole genome (GenBank accession number: OP512542), we found that its overall structure was not greatly changed compared with that of the previous strain Ea (KX423960.1). The whole genome alignment showed that XJ5 had a strong genetic relationship with the strains isolated in China after 2012 reported in GenBank. Based on the isolation time of XJ5 and the mutation and recombination analysis of programs, we found that the whole genome homology of XJ5 and other strains with Chinese isolates was greater than 95%, while the homology with strains outside Asia was less than 94%, which indicated that there may be some recombination and mutation patterns. We found that virulent PRV isolates emerged successively in China in 2011 and formed two different evolutionary clades from foreign isolates. At the same time, this may be due to improper immunization and the presence of wild strains in the field, and recent reports have confirmed that Bartha vaccine strains recombine with wild strains to obtain new pathogenic strains. We performed genetic evolution analysis of XJ5 isolated and sequenced in our laboratory to trace its possible mutations and recombination. We found that XJ5 may be the result of natural mutation of a virus in a branch of mutant strains widely existing in China.

Background Serum corin has been associated with stroke in observational studies, but the underlying causality is uncertain. This study examined the causal association between corin and stroke through Mendelian randomization study. Methods and Results In the Gusu cohort, serum corin was assayed at baseline, and stroke incidents were prospectively obtained during 10 years of follow‐up. Single‐nucleotide polymorphisms (SNPs) in CORIN were genotyped by MassArray for 2310 participants (mean age, 53 years; 39% men). Seventeen SNPs passed the Hardy–Weinberg test and were considered the potential instruments. Only 1 SNP (rs2271037) determined variability of serum corin was significantly associated with stroke even after adjusting for conventional risk factors (hazard ratio [HR], 1.36 [95% CI, 1.00–1.85]). The weighted genetic risk score generated from the SNP‐corin associations was significantly associated with stroke (HR, 2.01 [95% CI, 1.15–3.51]). Using this genetic risk score as the instrument, 1‐sample Mendelian randomization analysis found a significant HR of stroke per‐SD higher log2‐transformed corin (HR, 1.37 [95% CI, 1.07–1.76]). The inverse variance–weighted analysis based on the SNP‐corin and SNP‐stroke associations found that the HR of stroke pre‐SD higher log2‐transformed corin was 5.92 (95% CI, 2.23–15.72). The effect estimates stayed consistent regardless of an individual SNP being removed from the instruments. An almost identical effect estimate was also confirmed by multiple other 2‐sample Mendelian randomization methods. Conclusions Genetically determined variations of serum corin concentration were significantly associated with the risk of stroke in Chinese adults. Elevated serum corin may be a risk factor for stroke.

Panpan Xu,1– 3 Yu Cao,1– 3 Ruiqing Ren,1– 3 Shuai Zhang,1– 3 Cheng Zhang,1– 3 Panpan Hao,1– 3 Meng Zhang1– 3 1State Key Laboratory for Innovation and Transformation of Luobing Theory, Jinan, People’s Republic of China; 2Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Jinan, People’s Republic of China; 3Department of Cardiology, Qilu Hospital of Shandong University, Jinan, People’s Republic of ChinaCorrespondence: Meng Zhang; Panpan Hao, Department of Cardiology, Qilu Hospital of Shandong University, No. 107, Wenhuaxi Road, Jinan, Shandong, 250012, People’s Republic of China, Email zhangmeng@sdu.edu.cn; panda.how@sdu.edu.cnPurpose: The systemic inflammation response index (SIRI) and the systemic immune inflammation index (SII) are indicators that reflect the body’s overall systemic inflammatory response. Inflammation plays an important role in the pathogenesis of in-stent restenosis (ISR). The aim of this study was to investigate the predictive value of preoperative SIRI and SII for the occurrence of ISR in patients undergoing coronary stent implantation.Materials and Methods: We retrospectively analyzed the clinical, hematological, and angiographic data of 387 patients who underwent coronary angiography for recurrent angina after coronary stent implantation at Qilu Hospital of Shandong University. Receiver operating characteristic curve (ROC) analysis was used to determine the optimal cutoff values for SIRI and SII to predict ISR. Based on the optimal cutoff values for SIRI and SII, patients were categorized into high-SIRI, low-SIRI, high-SII, and low-SII groups. Multivariate logistic regression models were constructed to assess the predictive value of SIRI and SII for ISR > 50% and ISR > 70%.Results: This study included a total of 387 patients who underwent coronary angiography and follow-up at Qilu Hospital of Shandong University. Patients in the high-SIRI group had a higher incidence of ISR than those in the low-SIRI group (ISR > 50%: 44.8% vs 30.7%, p = 0.018; ISR > 70%: 41.5% vs 4.5%, p < 0.001). In addition, ISR occurred more frequently in patients with a higher SII than in patients with a lower SII (ISR > 50%: 52.6% vs 35.7%, p = 0.001; ISR > 70%: 51.9% vs 23%, p < 0.001). In multivariate logistic regression analysis, SIRI and SII were found to be independent predictive factors for ISR, both as continuous and categorical variables. In the ROC analysis, the optimal cutoff value for SIRI was set at 0.54 (sensitivity: 84.5%, specificity: 27%), and the optimal cutoff value for SII was set at 545.29 (sensitivity: 44.1%, specificity: 71.7%).Conclusion: Elevated preoperative SIRI and SII values help predict ISR and may serve as a useful screening tool to perform interventional procedures based on the patient’s risk of ISR after stent implantation.Keywords: SIRI, SII, in-stent restenosis, percutaneous coronary intervention

Abstract More than 90% of hepatocellular carcinoma (HCC) cases develop in the presence of fibrosis or cirrhosis, making the tumor microenvironment (TME) of HCC distinctive due to the intricate interplay between cancer-associated fibroblasts (CAFs) and cancer stem cells (CSCs), which collectively regulate HCC progression. However, the mechanisms through which CSCs orchestrate the dynamics of the tumor stroma during HCC development remain elusive. Our study unveils a significant upregulation of Sema3C in fibrotic liver, HCC tissues, peripheral blood of HCC patients, as well as sorafenib-resistant tissues and cells, with its overexpression correlating with the acquisition of stemness properties in HCC. We further identify NRP1 and ITGB1 as pivotal functional receptors of Sema3C, activating downstream AKT/Gli1/c-Myc signaling pathways to bolster HCC self-renewal and tumor initiation. Additionally, HCC cells-derived Sema3C facilitated extracellular matrix (ECM) contraction and collagen deposition in vivo, while also promoting the proliferation and activation of hepatic stellate cells (HSCs). Mechanistically, Sema3C interacted with NRP1 and ITGB1 in HSCs, activating downstream NF-kB signaling, thereby stimulating the release of IL-6 and upregulating HMGCR expression, consequently enhancing cholesterol synthesis in HSCs. Furthermore, CAF-secreted TGF-β1 activates AP1 signaling to augment Sema3C expression in HCC cells, establishing a positive feedback loop that accelerates HCC progression. Notably, blockade of Sema3C effectively inhibits tumor growth and sensitizes HCC cells to sorafenib in vivo. In sum, our findings spotlight Sema3C as a novel biomarker facilitating the crosstalk between CSCs and stroma during hepatocarcinogenesis, thereby offering a promising avenue for enhancing treatment efficacy and overcoming drug resistance in HCC.

Abstract The mitogen-activated protein kinase (MAPK) cascade MEK2-SIPK/WIPK is essential for immunity in Solanaceae plants. This cascade is tightly controlled to prevent harmful hyperactivation. However, the E3 ubiquitin ligases utilized by plants to reduce MEK2- SIPK/WIPK protein levels remain largely elusive. Here, we confirmed the essential role of Nicotiana benthamiana MEK2-SIPK/WIPK in resistance to the oomycete pathogen Phytophthora capsici. Using tobacco rattle virus (TRV)-based gene silencing, we screened prevalent plant U-box protein (PUB)-type E3 ligases with Armadillo (ARM) repeats to characterize those involved in Phytophthora resistance and MEK2-SIPK/WIPK degradation. We found that pub40 knockdown mutants exhibited significantly enhanced resistance to P. capsici. NbPUB40 was under ubiquitination and proteasomal degradation in planta, with two conserved sites (Cys28 and Val41) in the U-box domain being essential for its activity. NbPUB40 was shown to interact with the whole MEK2-SIPK/WIPK cascade and promote their degradation, the ubiquitination levels of which were also notably reduced in the pub40 mutant. Our results reveal a mechanism in which a PUB E3 ubiquitin ligase negatively regulates plant P. capsici resistance by destabilizing the MEK2-SIPK/WIPK cascade.

Abstract Background Assessing the aggressiveness of pure ground glass nodules early on significantly aids in making informed clinical decisions. Objective Developing a predictive model to assess the aggressiveness of pure ground glass nodules in lung adenocarcinoma is the study’s goal. Methods A comprehensive search for studies on the relationship between computed tomography(CT) characteristics and the aggressiveness of pure ground glass nodules was conducted using databases such as PubMed, Embase, Web of Science, Cochrane Library, Scopus, Wanfang, CNKI, VIP, and CBM, up to December 20, 2023. Two independent researchers were responsible for screening literature, extracting data, and assessing the quality of the studies. Meta-analysis was performed using Stata 16.0, with the training data derived from this analysis. To identify publication bias, Funnel plots and Egger tests and Begg test were employed. This meta-analysis facilitated the creation of a risk prediction model for invasive adenocarcinoma in pure ground glass nodules. Data on clinical presentation and CT imaging features of patients treated surgically for these nodules at the Third Affiliated Hospital of Kunming Medical University, from September 2020 to September 2023, were compiled and scrutinized using specific inclusion and exclusion criteria. The model’s effectiveness for predicting invasive adenocarcinoma risk in pure ground glass nodules was validated using ROC curves, calibration curves, and decision analysis curves. Results In this analysis, 17 studies were incorporated. Key variables included in the model were the largest diameter of the lesion, average CT value, presence of pleural traction, and spiculation. The derived formula from the meta-analysis was: 1.16×the largest lesion diameter + 0.01 × the average CT value + 0.66 × pleural traction + 0.44 × spiculation. This model underwent validation using an external set of 512 pure ground glass nodules, demonstrating good diagnostic performance with an ROC curve area of 0.880 (95% CI: 0.852–0.909). The calibration curve indicated accurate predictions, and the decision analysis curve suggested high clinical applicability of the model. Conclusion We established a predictive model for determining the invasiveness of pure ground-glass nodules, incorporating four key radiological indicators. This model is both straightforward and effective for identifying patients with a high likelihood of invasive adenocarcinoma.

Abstract The prevalence of thyroid dysfunction diseases (TDFDs) and osteoporosis (OP) is high. Previous studies have indicated a potential association between TDFDs and OP, yet the causal direction remains unclear. This study aimed to investigate the potential causal relationship between TDFDs and the risk of developing OP and related fractures. We obtained pooled data from genome-wide association studies (GWASs) conducted on TDFDs and OP in European populations and identified single-nucleotide polymorphisms (SNPs) with genome-wide significance levels associated with exposure to TDFDs as instrumental variables. Inverse variance weighted (IVW) was employed as the primary method for Mendelian randomization (MR) analysis, supplemented by MR‒Egger, weighted median, simple mode and weighted mode methods. Sensitivity analyses were conducted to evaluate the robustness of the findings. The IVW method demonstrated an increased risk of OP in patients with TDFDs, including hyperthyroidism and hypothyroidism (TDFDs: OR = 1.11; 95% CI 1.09, 1.13; hypothyroidism: OR = 1.14; 95% CI 1.10, 1.17; hyperthyroidism: OR = 1.09; 95% CI 1.06, 1.12). These findings were supported by supplementary analysis, which revealed a positive correlation between TDFDs and the risk of OP. Multiple sensitivity analyses confirmed the absence of horizontal pleiotropy in the study, thus indicating the robustness of our results. The causal relationship between TDFDs and increased risk of OP implies the need for early bone mineral density (BMD) screening and proactive prevention and treatment strategies for individuals with TDFDs.

Bulb rot of lily (Lilium brownii var. viridulum), caused by Fusarium commune, is a serious soilborne disease of lily plants. In this study, several bacterial isolates were obtained from the rhizosphere of healthy lily plants and evaluated for biocontrol potential. Among the obtained isolates, GX1 had the highest level of antifungal activity in vitro, inhibiting the growth of F. commune by 52.0 %, relative to the control (CK). The isolate was identified as Bacillus velezensis based on its morphology and 16S rRNA and gyrB gene sequence analysis. The fermentation broth of GX1 after 12 d of fermentation at 25 °C (pH 7) exhibited strong antifungal activity. A crude lipopeptide extracts of GX1 fermentation broth was as effective (50.3 %) at inhibiting the mycelial growth of F. commune as living cultures of GX1. GX1 possesses fenD, bmyB, srfAA and bacA antimicrobial peptide (AMP) genes, which may be the primary source of its antifungal activity. GX1 significantly reduced the disease severity index of lily bulb rot in pot experiments, indicating that B. velezensis GX1 has substantial potential for the biological control of lily bulb rot.

Lactiplantibacillus plantarum strains are potentially rich sources of probiotics that could help avoid infections. In order to evaluate their efficacy in bolstering resistance to Salmonella typhimurium infection among chicks. In this study, L. plantarum and commercial probiotics were administered via the water supply at a dosage of 1×109 CFU per chicken from days 1 to 7 to establish a protective system for the chicks. On days 8 and 9, S. typhimurium was attacked to investigate the preventive effects and potential mechanisms of L. plantarum in comparison with commercial probiotics. Post-treatment, we took a broad range of measurements, including body weight, immune organ index changes, the viable count of S. typhimurium in the liver, spleen, and cecum, as well as pathological changes in the liver. Our findings demonstrated that both L. plantarum and the commercial probiotic could safeguard chicks from S. typhimurium infection. The data also suggested that probiotic medication could ease weight loss postinfection, lower the bacterial count in the liver, spleen, and cecum, and attenuate liver pathological damage among all treated participants. Subsequently, we did high-throughput sequencing of 16S rRNA to examine the fecal microbiota of the chicks 5 days post-infection. We discovered that both L. plantarum and the commercial probiotic could fend off the invasion of S. typhimurium by affecting the bacterial population of Anaerotruncus, Colidextribacter, and Lactobacillus. Generally speaking, the addition of L. plantarum as a feed additive protects yellow-feathered broilers from S. typhimurium illness, suggesting great potential for commercial uses in the poultry industry.

Background The association of lipid‐lowering drug targets and their gene variants with cardiovascular diseases has been previously clarified. However, the relationship between gene variants of lipid‐lowering drug targets and the adverse prognosis of ischemic stroke patients remains unclear. Methods and Results Multiple single‐nucleotide polymorphisms associated with 6 lipid‐lowering drug targets were genotyped for patients with ischemic stroke. The primary outcome was death or major disability within 2 years after ischemic stroke. Genetic risk score was constructed from significant single‐nucleotide polymorphisms identified via additive models, which was calculated by multiplying the number of risk alleles at each locus by the corresponding beta coefficient and then summing the products. The rs2006760‐C of the HMGCR, rs11206510‐T of PCSK9, and rs1864163‐G and rs9929488‐G of CETP were associated with increased odds of adverse outcomes within 2 years after ischemic stroke. Each additional risk allele was associated with higher odds of adverse outcomes. Genetic risk score was positively associated with the odds of primary outcome (odds ratio [OR], 1.48 [95% CI, 1.15–1.90]; Ptrend = 0.001), major disability (OR, 1.56 [95% CI, 1.16–2.08]; Ptrend = 0.002), death (hazard ratio [HR], 1.58 [95% CI, 1.12–2.25]; Ptrend = 0.011), and the composite outcome of death or cardiovascular events (HR, 1.41 [95% CI, 1.08–1.85]; Ptrend = 0.010) when 2 extreme quartiles were compared. Conclusions rs2006760‐C of HMGCR, rs11206510‐T of PCSK9, and rs1864163‐G and rs9929488‐G of CETP were associated with increased odds of adverse outcomes within 2 years after ischemic stroke. Furthermore, higher GRS was positively related to the odds of poor outcomes in patients with ischemic stroke. Registration: URL: https://www.clinicaltrials.gov; Identifier: NCT01840072.

Abstract In this study, a deep learning model based on quantum chemistry is introduced to enhance the accuracy and efficiency of predicting DNA reaction parameters. By integrating quantum chemical calculations with self‐designed descriptor matrices, the model offers a comprehensive description of energy variations and considers a broad range of relevant factors. To overcome the challenge of limited labeled data, an active learning method is employed. The results demonstrate that this model outperforms existing methods in predicting DNA hybridization free energies and strand displacement rate constants, thus advancing the understanding of DNA molecular interactions, and aiding in the precise design and optimization of DNA‐based systems.

In the past, the use of remote sensing for winter wheat growth monitoring mainly relied on the relative growth assessment of a single vegetation index, such as normalized Vegetation index (NDVI). This study advanced the methodology by integrating field-measured data with Sentinel-2 data. In addition to NDVI, it innovatively incorporated two parameters, aboveground biomass (AGB) and leaf area index (LAI), for a more comprehensive relative growth assessment. Furthermore, the study employed the agricultural production systems simulator (APSIM) model to use LAI and AGB for absolute growth monitoring. The results showed that the simulated LAI and AGB closely match the field-measured values throughout the entire growth period of winter wheat under various conditions (R2 > 0.9). For relative growth monitoring, NDVI showed significant linear positive correlations (r > 0.74 and P< 0.05) with both LAI and AGB simulated by the APSIM model. Overall, this research shows that LAI and AGB obtained from the APSIM model provide a more detailed and accurate approach to monitoring of winter wheat growth. This improved monitoring capability can support effective land management arable and provide technical guidance to advance precision agriculture practices.

Nuclear receptors (NRs) are key regulators of multiple physiological functions and pathological changes in the liver in response to a variety of extracellular signaling changes. Retinoid X receptor (RXR) is a special member of the NRs, which not only responds to cellular signaling independently, but also regulates multiple signaling pathways by forming heterodimers with various other NR. Therefore, RXR is widely involved in hepatic glucose metabolism, lipid metabolism, cholesterol metabolism and bile acid homeostasis as well as hepatic fibrosis. Specific activation of particular dimers regulating physiological and pathological processes may serve as important pharmacological targets. So here we describe the basic information and structural features of the RXR protein and its heterodimers, focusing on the role of RXR heterodimers in a number of physiological processes and pathological imbalances in the liver, to provide a theoretical basis for RXR as a promising drug target.

Traditionally, extracting single, flat- or curved-rooted teeth through twisting is unfeasible. However, our clinical practice suggests that such teeth can be extracted efficiently through moderate twisting in a minimally invasive manner. Given the lack of studies on biomechanics of the tooth–periodontal ligament (PDL) complex during torsion, which has further constrained its application, we assessed the feasibility of the torsion method for extracting single-rooted teeth and evaluated its minimally invasive potential. Using three-dimensional finite element analysis, we examined the stress distribution of the tooth and PDL during torsion. Then, we examined changes in the optimal torsion angle (OTA) and stress distribution across various anatomical scenarios. During torsion loading, stress concentration was primarily observed on the sing-rooted tooth surface near the alveolar crest, whereas molars at the root furcation. The OTA was found to increase under conditions such as narrowing of root width, decrease in the root apical curvature, change from type I to IV bone, alveolar bone loss, and shortening of root length. Moreover, the clinically validated model demonstrated that 74% of outcomes fell within the standard OTA range. In conclusion, the decrease in PDL area necessitated a larger angle for complete PDL tearing. Single-rooted teeth with root width-to-thickness ratios of ≥0.42 and apical curvatures of ≤30°are suitable for extraction using the torsion method. This study confirms the feasibility of the torsion method for minimally invasive tooth extraction and expands its indications, laying the theoretical foundation and essential insights for its clinical application.

IntroductionBone marrow mesenchymal stem cells (BMSCs) are widely used in tissue engineering and regenerative medicine as seed cells. Due to low amount in bone marrow, BMSCs must be expanded and cultured in vitro before application. However, the senescence of stem cell caused by long-term in vitro culture greatly limits its efficacy of transplantation.MethodsIn this study, we propose an approach based on electromagnetic fields (EMF) treatment to rejuvenate aged BMSCs due to long-term in vitro culture. Aged BMSCs were treated with sinusoidal EMF (50 Hz, 0.4 mT), and stem cell senescence, cell proliferation, cell differentiation, cell stemness and autophagy level were detected. Additionally, aged BMSCs-laden hydrogels were transplanted into the rat critical-sized calvarial defect with or without EMF treatment. The bone formation was evaluated 8 weeks after surgery.ResultsOur results indicated that the BMSCs age significantly after long-term in vitro passaging. The self-renew, multiple differentiation capacity, senescence phenotypes and stemness of aged BMSCs are partly reversed by EMF treatment with a frequency of 50 Hz and strength of 0.4 mT. Moreover, declined autophagy level is observed in BMSCs during long-term in vitro passaging and BMSCs senescence is closely associated with autophagy regulation. Additionally, the mechanistic investigation reveals that EMF treatment rejuvenate senescent BMSCs by enhancing autophagy. Furthermore, EMF treatment significantly promote the therapeutic effect of long-term passaged BMSCs on bone formation in vivo.ConclusionOverall, our study identifies a practical approach for the rejuvenation of old BMSCs and may provide a promising candidate in tissue engineering and stem cell therapy.

Background Antiphospholipid antibodies (aPLs) have been reported to be involved in platelet‐mediated thrombosis and inflammation, but the impact on the prognosis of ischemic stroke remains unclear. We aimed to examine whether the association between baseline platelet count (PLT) and long‐term clinical outcomes within 2 years after ischemic stroke onset is modulated by aPLs. Methods and Results A total of 2938 patients with ischemic stroke were included in this prospective cohort study. Cox proportional hazards regression models were used to assess the association between the baseline PLT stratified by aPLs status and 2‐year clinical outcomes after stroke onset, and an interaction effect between PLT and aPLs on clinical outcomes was tested by likelihood ratio test. There was a significant interaction effect of aPLs and PLT on recurrent stroke (Pinteraction=0.002) and cardiovascular events (Pinteraction=0.001) within 2 years after stroke onset. After multivariate adjustment, high PLT was associated with increased risks of recurrent stroke (hazard ratio [HR], 2.78 [95% CI, 1.03–7.45]; Ptrend=0.039) and cardiovascular events (HR, 2.58 [95% CI, 1.12–5.90]; Ptrend=0.024) when 2 extreme tertiles were compared among patients with aPL positive, but not among those with aPL negative. Conclusions The aPLs had a modifying effect on the association between PLT and clinical outcomes within 2 years after ischemic stroke onset. Increased PLT was associated with recurrent stroke and cardiovascular events after ischemic stroke onset among patients with aPL positive, but not in those with aPL negative.

Esophageal cancer ranks among the most prevalent malignant tumors globally. The prognosis for esophageal squamous cell carcinoma remains poor, with a 5-year survival rate below 20 % due to limited advances in therapy. Ferroptosis, a novel form of iron-dependent lipid peroxidation-driven regulated cell death (RCD), shows significant promise in cancer treatment. Berbamine (BBM), a natural bisbenzylisoquinoline alkaloid derived from Berberis amurensis, exhibits anti-tumor effects against various cancers, yet its impact on esophageal cancer remains to be elucidated. This study aimed to explore the role of BBM in inducing ferroptosis in the treatment of esophageal cancer, focusing on its molecular mechanisms. Gene set enrichment analysis(GSEA) analysis highlighted the potential of BBM as an anti-cancer agent through ferroptosis induction. We found that BBM inhibited growth and epithelial-mesenchymal transition (EMT) in esophageal cancer cell lines, promoting Fe accumulation, ROS, and malondialdehyde (MDA) production, thereby triggering cell death. These suppressive effects were successfully reversed by Ferrostatin-1 (Fer-1). Mechanistically, BBM decreased deubiquitination enzyme USP51 levels, leading to ubiquitin degradation and glutathione peroxidase 4(GPX4) instability, and it stimulated ferroptosis. The Overexpression of USP51 mitigated the downregulation of GPX4 induced by BBM.BBM significantly inhibited tumor xenograft growth in nude mice. This discovery positions BBM as a promising therapeutic candidate for the treatment of esophageal cancer.

Abstract Precise identification of glioblastoma (GBM) microinfiltration, which is essential for achieving complete resection, remains an enormous challenge in clinical practice. Here, the study demonstrates that Raman spectroscopy effectively identifies GBM microinfiltration with cellular resolution in clinical specimens. The spectral differences between infiltrative lesions and normal brain tissues are attributed to phospholipids, nucleic acids, amino acids, and unsaturated fatty acids. These biochemical metabolites identified by Raman spectroscopy are further confirmed by spatial metabolomics. Based on differential spectra, Raman imaging resolves important morphological information relevant to GBM lesions in a label‐free manner. The area under the receiver operating characteristic curve (AUC) for Raman spectroscopy combined with machine learning in detecting infiltrative lesions exceeds 95%. Most importantly, the cancer cell threshold identified by Raman spectroscopy is as low as 3 human GBM cells per 0.01 mm2. Raman spectroscopy enables the detection of previously undetectable diffusely infiltrative cancer cells, which holds potential value in guiding complete tumor resection in GBM patients.

IntroductionHigh-resolution whole-heart coronary magnetic resonance angiography (CMRA) often suffers from unreasonably long scan times, rendering imaging acceleration highly desirable. Traditional reconstruction methods used in CMRA rely on either hand-crafted priors or supervised learning models. Although the latter often yield superior reconstruction quality, they require a large amount of training data and memory resources, and may encounter generalization issues when dealing with out-of-distribution datasets.MethodsTo address these challenges, we introduce an unsupervised reconstruction method that combines deep image prior (DIP) with compressed sensing (CS) to accelerate 3D CMRA. This method incorporates a slice-by-slice DIP reconstruction and 3D total variation (TV) regularization, enabling high-quality reconstruction under a significant acceleration while enforcing continuity in the slice direction. We evaluated our method by comparing it to iterative SENSE, CS-TV, CS-wavelet, and other DIP-based variants, using both retrospectively and prospectively undersampled datasets.ResultsThe results demonstrate the superiority of our 3D DIP-CS approach, which improved the reconstruction accuracy relative to the other approaches across both datasets. Ablation studies further reveal the benefits of combining DIP with 3D TV regularization, which leads to significant improvements of image quality over pure DIP-based methods. Evaluation of vessel sharpness and image quality scores shows that DIP-CS improves the quality of reformatted coronary arteries.DiscussionThe proposed method enables scan-specific reconstruction of high-quality 3D CMRA from a five-minute acquisition, without relying on fully-sampled training data or placing a heavy burden on memory resources.

Background and objective: The intrinsic link between the compositional and structural attributes and the biomechanical functionality is evident in intervertebral discs. However, it remains unclear from a biomechanical perspective whether cartilage endplate (CEP) degeneration exacerbates intervertebral disc degeneration. Methods: This study developed and quantitatively validated four biphasic swelling-based finite element models. We then applied four quasi-static tests and simulated daily loading scenarios to examine the effects of CEP degradation. Results: Under free-swelling conditions, short-term responses were prevalent, with CEP performance changes not significantly impacting response proportionality. The creep test results showed the more than 50 % of the strain was attributed to long-term responses. Stress-relaxation testing indicated that all responses increased with disc degeneration, yet CEP degeneration's impact was minimal. Daily load analyses revealed that disc degeneration significantly reduces nucleus pulposus pressure and disc height, whereas CEP degeneration marginally increases nucleus pressure and slightly decreases disc height. Conclusions: Glycosaminoglycan content and CEP permeability are critical to the fluid-dependent viscoelastic response of intervertebral discs. Our findings suggest that CEP contributes to disc degeneration under daily loading conditions.

Studying contaminant transport in the capillary fringe (CF), a crucial part of the vadose zone, offers insights into the mechanisms controlling pollution in soils and groundwater aquifers. This paper investigated contaminant transport in the CF by continuously injecting a conservative tracer (NaCl) and graphene oxide nanoparticle (GONP), an adsorptive contaminant, into a sandbox. After entering the CF from the unsaturated zone, both NaCl and GONP underwent lateral transport. The breakthrough curves (BTCs) for NaCl and GONP were derived from water samples collected at predetermined sampling holes. Subsequently, contaminant transport in the CF was modeled using a one-dimensional–two-dimensional (1D-2D) coupled hydrodynamic model. This model incorporated lateral dispersivity (αL = 1.198 cm) and longitudinal dispersivity (αT = 0.286 cm), calculated using a point-by-point method. The hydrodynamic dispersion coefficients obtained were then applied to the Brooks and Corey (BC) and the van Genuchten (VG) parametric models. The BC model more accurately simulated the NaCl migration compared to the VG model, leading to its application in simulating GONP transport in the CF. However, the simulated BTCs for GONP showed a lag behind the measured data, especially at high ionic strengths. This discrepancy was attributed to the variable adsorption partition coefficient of GONP under different ionic conditions. During the experiment, GONP adsorption onto the porous media's surface altered the capillary dynamics, notably increasing capillary rise height, decreasing seepage velocity, and reducing GONP dispersion. Therefore, it is necessary to consider the adsorption capacity of the contaminants in order to accurately assess their transport within the vadose zone.

China is the largest coke producer and consumer. There is a pressing need to address the high emissions of air pollutants and carbon dioxide associated with traditional coking production. As the nation pursues a transition towards carbon neutrality, expanding supply chains for coking plants to produce hydrogen, methanol, and other green alternatives has garnered significant attention. However, the relative advantages of these strategies have remained uncertain. In this study, we integrate a life cycle assessment-economic analysis-scenario analysis model to evaluate various coke oven gas (COG) utilization routes (COGtM: COG-to-methanol, COGtLNG: COG-to-liquefied natural gas, COGtSA: COG-to-synthetic ammonia, and COGtH: COG-to-hydrogen). The results indicate that COGtSA emerges as the preferred option for balancing environmental and economic benefits. Meanwhile, COGtM demonstrates economic viability but is associated with higher environmental impacts. Despite being recognized as a significant strategic direction under carbon neutrality initiatives, COGtH faces economic feasibility and risk resilience limitations. COGtLNG encounters both financial and environmental challenges, necessitating strategic development from an energy security perspective. The projected coking capacity is anticipated to experience a slight increase in the mid-term yet a significant decline in the long term, influenced by steel production capacity. In potential future markets, COGtM is estimated to potentially capture a maximum market share of 16–34% in the methanol market. Furthermore, against the backdrop of continuously expanding potential demand for hydrogen, COGtH holds advantages as a transitional solution, but in the long run, it can only meet a small portion of the market. COGtSA can meet 7–14% of market demand and emerges as the most viable pathway from the viewpoint of balancing environmental and economic aspects and covering future markets.

Abstract It is very challenging to accurately segment smoke images because smoke has some adverse vision characteristics, such as anomalous shapes, blurred edges, and translucency. Existing methods cannot fully focus on the texture details of anomalous shapes and blurred edges simultaneously. To solve these problems, a Dense Multi‐scale context and Asymmetric pooling Embedding Network (DMAENet) is proposed to model the smoke edge details and anomalous shapes for smoke segmentation. To capture the feature information from different scales, a Dense Multi‐scale Context Module (DMCM) is proposed to further enhance the feature representation capability of our network under the help of asymmetric convolutions. To efficiently extract features for long‐shaped objects, the authors use asymmetric pooling to propose an Asymmetric Pooling Enhancement Module (APEM). The vertical and horizontal pooling methods are responsible for enhancing features of irregular objects. Finally, a Feature Fusion Module (FFM) is designed, which accepts three inputs for improving performance. Low and high‐level features are fused by pixel‐wise summing, and then the summed feature maps are further enhanced in an attention manner. Experimental results on synthetic and real smoke datasets validate that all these modules can improve performance, and the proposed DMAENet obviously outperforms existing state‐of‐the‐art methods.

Abstract Background The traditional surgical procedures for upper lumbar disc herniation (ULDH) usually lead to frequent complications. We aim to investigate the clinical efficacy of the unilateral biportal endoscopy (UBE) technique in treating upper lumbar disc herniation (ULDH). Methods From January 2020 to December 2021, the clinical data of 28 patients with ULDH treated with the UBE technique were collected and analyzed for surgery time under UBE, postsurgical drainage, postsurgical hospital stay, and complications. The clinical efficacy was evaluated according to the modified MacNab score, Oswestry disability index (ODI), and visual analogue scale (VAS) of low back pain and lower limb pain before the surgery; one week, one month, and three months after the surgery; and at the last follow-up. Results All patients underwent the UBE surgery successfully. The surgery time under UBE for non-fusion cases was 47.50 ± 11.84 min (monosegment) and 75.00 ± 20.66 min (two segments), while that for fusion cases was 77.50 ± 21.02 min. The postsurgical drainage for non-fusion cases was 25.00 ± 13.94 mL (monosegment) and 38.00 ± 11.83 mL (two segments), while that for fusion cases was 71.25 ± 31.72 mL. The postsurgical hospital stay was 8.28 ± 4.22 days. The follow-up time was 15.82 ± 4.54 months. The VAS score for each time period after the surgery was significantly lower (P

Abstract Stabilization of topological spin textures in layered magnets has the potential to drive the development of advanced low-dimensional spintronics devices. However, achieving reliable and flexible manipulation of the topological spin textures beyond skyrmion in a two-dimensional magnet system remains challenging. Here, we demonstrate the introduction of magnetic iron atoms between the van der Waals gap of a layered magnet, Fe3GaTe2, to modify local anisotropic magnetic interactions. Consequently, we present direct observations of the order-disorder skyrmion lattices transition. In addition, non-trivial topological solitons, such as skyrmioniums and skyrmion bags, are realized at room temperature. Our work highlights the influence of random spin control of non-trivial topological spin textures.

In order to realize in-situ, green and large-scale disposal of coal gangue, coal gangue slurry filling technology, as a new filling technology, has been rapidly developed and applied in recent years. This paper systematically reviews and summarizes the landmark achievements and key technologies of coal gangue slurry filling at different stages, such as the proposal of the technical framework, the formation of the theoretical system of slurry filling, the application of engineering demonstration and the innovation of technology iteration, and forms three filling methods, namely, high-level grouting, low-level grouting and adjacent grouting. The “intervention theory” of coal gangue slurry flow in goaf caving zone and the “three degrees and one field” theory of slurry pipeline transportation have been established, and the first demonstration project of coal gangue underground slurry filling and surface slurry preparation + underground adjacent grouting filling has been successfully carried out at home and abroad; This paper expounds the technical system of coal gangue slurry filling, and discusses the key technical core issues of coal gangue high-efficiency grading crushing, slurry precise preparation, slurry pipeline transportation and end filling, focusing on the process flow of coal gangue crushing, water slurrying of finished gangue powder, slurry pumping preparation and underground target area filling. The technical principles and application scenarios of key equipment such as crushing equipment, screening equipment, metering equipment, mixing equipment and pumping equipment are analyzed; Based on the engineering background of small space, multi-equipment and high capacity of coal gangue slurry filling in Zhangjiamao Coal Mine, the layout of different systems such as surface slurry making, pipeline transportation, underground filling and intelligent control of coal gangue slurry filling was innovatively developed and designed, and the annual filling amount of coal gangue could reach 554 000 tons, forming a demonstration of coal gangue slurry filling engineering. In the future, the coal gangue slurry filling technology will be further studied and developed in the direction of small and lightweight equipment, highly integrated system, iterative and innovative technology, which will provide technical support for the construction of green coal mining technology system and the realization of the national carbon peaking and carbon neutrality goal.

Abstract The progression of human degenerative and hypoxic/ischemic diseases is accompanied by widespread cell death. One death process linking iron-catalyzed reactive species with lipid peroxidation is ferroptosis, which shows hallmarks of both programmed and necrotic death in vitro. While evidence of ferroptosis in neurodegenerative disease is indicated by iron accumulation and involvement of lipids, a stable marker for ferroptosis has not been identified. Its prevalence is thus undetermined in human pathophysiology, impeding recognition of disease areas and clinical investigations with candidate drugs. Here, we identified ferroptosis marker antigens by analyzing surface protein dynamics and discovered a single protein, Fatty Acid-Binding Protein 5 (FABP5), which was stabilized at the cell surface and specifically elevated in ferroptotic cell death. Ectopic expression and lipidomics assays demonstrated that FABP5 drives redistribution of redox-sensitive lipids and ferroptosis sensitivity in a positive-feedback loop, indicating a role as a functional biomarker. Notably, immunodetection of FABP5 in mouse stroke penumbra and in hypoxic postmortem patients was distinctly associated with hypoxically damaged neurons. Retrospective cell death characterized here by the novel ferroptosis biomarker FABP5 thus provides first evidence for a long-hypothesized intrinsic ferroptosis in hypoxia and inaugurates a means for pathological detection of ferroptosis in tissue.

Yang Bo, Xiaojing Zhong, Yanping Xiang, Qingjun Ren, Pingsheng Hao Department of Dermatology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of ChinaCorrespondence: Pingsheng Hao, Department of Dermatology, Hospital of Chengdu University of Traditional Chinese Medicine, 39 Shi-Er-Qiao Road, Jinniu District, Chengdu, Sichuan, 610072, People’s Republic of China, Tel +86138 8196 5024, Fax +86-28-87732407, Email hpswl@126.comAbstract: We report a fatal case of disseminated herpes zoster in a patient with multiple myeloma, illustrating the severe risks immunocompromised individuals face from viral infections. By combining a detailed case report with an extensive literature review, the paper seeks to shed light on the underlying susceptibility factors for varicella-zoster virus infection in multiple myeloma patients. We further evaluate effective prophylactic protocols for herpes zoster, aiming to equip clinicians with improved therapeutic strategies. The case underscores the critical need for vigilant clinical assessments and tailored patient management to mitigate infection risks and enhance patient outcomes.Keywords: multiple myeloma, disseminated herpes zoster, antiviral prophylaxis, immunodeficiency