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Abstract Objectives Exploring the effect of resilience and self-efficacy in mediating the chain between fatigue and quality of life(QOL) in patients with rheumatoid arthritis (RA). Methods From June 2022 to November 2022, 423 RA patients were chosen by a convenience sample method from two tertiary care facilities in Chengdu, Sichuan Province. General Information Questionnaire, Bristol Multidimensional Scale of Fatigue in Patients with Rheumatoid Arthritis, SF−12 Health Survey Short Form, Chinese version of the ten-item psychological Resilience Scale, and Chinese-language Arthritis Self-Efficacy Scale, an 8-element version, were among the questionnaires used. Results In the physical component summary( PCS), self-efficacy, psychological resilience, and self-efficacy were all significantly mediated by fatigue (total effect mediated 8.88%). In the mental component summary (MCS), fatigue (total effect mediated 10.79%), self-efficacy (total effect mediated 8.99%), psychological resilience, and self-efficacy (total effect mediated 2.01%) were all significantly mediated by fatigue. Conclusion Fatigue in RA patients can affect the quality of life both directly and indirectly through the mediating effects of psychological resilience, self-efficacy, and the chain mediating effect of psychological resilience-self-efficacy.

Introduction: Surgical resection following systemic therapy is feasible in patients with initially unresectable hepatocellular carcinoma (HCC). However, postoperative tumor recurrence is common after surgery, and the factors affecting this recurrence remain unclear. This study aimed to assess factors influencing postoperative outcomes in patients with initially unresectable HCC undergoing hepatectomy after systemic therapy. Methods: This study retrospectively enrolled patients with initially unresectable HCC who underwent hepatectomy after targeted therapy plus immunotherapy (with or without locoregional therapy). Multivariate Cox regression analyses were used to identify the independent prognostic factors for recurrence-free survival (RFS) and overall survival (OS). Machine learning was used to determine the RFS rates at different intervals for different radiographic responses. Results: Eighty-one patients who underwent R0 hepatectomy after systemic therapy were included. With a median follow-up of 17.4 (interquartile range: 7.2–22.3) months, median RFS and OS were not reached. Preoperative tumor downstaging and achieving pathological complete response were associated with improved RFS and OS. Multivariate Cox analyses identified radiographic response as an independent prognostic factor for RFS and OS. Furthermore, a radiographic response >40% (assessed using the Response Evaluation Criteria in Solid Tumors, version 1.1) or >50% (assessed using the modified Response Evaluation Criteria in Solid Tumors) was associated with a longer RFS (P = 0.006 and 0.003, respectively). Conclusion: Radiographic response depth was an independent prognostic factor in patients with initially unresectable HCC who underwent hepatectomy following targeted therapy plus immunotherapy, and the response to systemic therapy may be the determining factor for patient prognosis after surgery.

The objective of this study was to examine the early serum proteomic and inflammatory profiles of weaned piglets subjected to iron deficiency. Twelve healthy piglets (Duroc × Landrace × Large Yorkshire, body weight: 4.96 ± 0.05 kg) were weaned at 21 days of age. Subsequently, these animals were randomly allocated to one of two groups, with six replicates in each group (maintaining a male-to-female ratio of 1:1), the control group (administered 100 mg/kg Fe as FeSO4·H2O) and L-Fe group (no additional Fe supplementation). The results showed that 42 days after initiating, compared with control group, routine blood analysis revealed a reduction in serum iron content, red blood cell (RBC) count, hemoglobin (HGB) content, hematocrit (HCT), and mean corpuscular volume (MCV) (P 0.05). During the early stages of iron deficiency, piglets exhibited increased villus height (VH) and the ratio of VH to crypt depth (CD) in the duodenum (P

Abstract The unmanned aerial vehicle (UAV) city patrol is of great significance in ensuring the safety of residents’ lives and properties, as well as maintaining the normal operation of the city. However, the detection of UAV images faces challenges such as numerous small-scale objects, complex backgrounds, and high requirements for detection speed. In response to these issues, we introduce a Real-time Small Object Detection network in UAV-vision (RTS-Net), tailored for UAV patrols. Initially, we introduce a multiscale feature fusion module (MFFM) designed to augment the expressiveness of features across scales, thereby enhancing the detection of smaller objects. Subsequently, leveraging attention mechanisms, we present the coordinated attention detection module (CADM), which bolsters the detection model’s ability to accurately segregate objects from the background in expansive, complex scenarios. Lastly, a lightweight real-time feature extraction module (RFEM) is crafted to diminish model computational complexity and boost inference speed. On the UAV road patrol image dataset we constructed, our proposed method attains a detection accuracy of 89.9 $$\%$$ % mAP, breaking previous records. It surpasses all prevailing detection methods, particularly for small-scale objects. Simultaneously, it achieves an inference speed of 163.9 FPS. The experimental results show that RTS-Net can satisfy the accurate and efficient detection of ground objects by various different UAV platforms in different complex scenarios.

Abstract In this study, the Xgboost method is employed for TOC estimation in mixed carbonate and siliciclastic shale from the Hashan area, Junggar Basin. The results show that this approach is effective for TOC estimation in this area although the model performance is not very excellent with a correlation coefficient of 0.54 between measured TOC and predicted TOC values, likely due to a small samples dataset. Therefore, the PCA method is applied to debase dimension of well log data from five dimensional to two-dimensional data, which enhances the correlation coefficient between the predicted and measured TOC from 0.54 to 0.68. Based on the model, the isopleth maps of TOC distributions in Fengcheng Formation were redrawn showing two shale oil exploration targets, which likely correspond to two depositional centers of this strata. All the same, the model in this work provides reliable data for shale oil evaluation in the study area and a good example under similar geological setting.

Abstract Accurately predicting the remaining useful life (RUL) of aircraft engines is crucial for maintaining financial stability and aviation safety. To further enhance the prediction accuracy of aircraft engine RUL, a deep learning-based RUL prediction method is proposed. This method possesses the potential to strengthen the recognition of data features, thereby improving the prediction accuracy of the model. First, the input features are normalized and the CMAPSS (Commercial Modular Aero-Propulsion System Simulation) dataset is utilized to calculate the RUL for aircraft engines. After extracting attributes from the input data using a convolutional neural network (CNN), the extracted data are input into a long short-term memory (LSTM) network model, with the addition of attention mechanisms to predict the RUL of aircraft engines. Finally, the proposed aircraft engine model is evaluated and compared through ablation studies and comparative model experiments. The results indicate that the CNN-LSTM-Attention model exhibits superior prediction performance for datasets FD001, FD002, FD003, and FD004, with RMSEs of 15.977, 14.452, 13.907, and 16.637, respectively. Compared with CNN, LSTM, and CNN-LSTM models, the CNN-LSTM model demonstrates better prediction performance across datasets. In comparison with other models, this model achieves the highest prediction accuracy on the CMAPSS dataset, showcasing strong reliability and accuracy.

Abstract Background Deep venous thrombosis (DVT) after spinal surgery has recently attracted increasing attention. Patients with spinal metastases who undergo decompression with fixation are at a high risk of developing DVT. D-dimer levels indicate the risk of DVT, and the purpose of our study was to investigate D-dimer levels as a predictor of DVT perioperatively. Methods We prospectively evaluated 100 patients with spinal metastases. D-dimer tests were performed twice: once before surgery and one day postoperatively. DVT was diagnosed by duplex ultrasonographic assessment of both lower extremities. Pulmonary embolisms (PEs) were diagnosed using multidetector computed tomography and pulmonary angiography. Perioperative serum D-dimer levels were compared between the DVT (+) and DVT (-) groups. The cutoff value of the D-dimer level was calculated using receiver operating characteristic analysis. Results Preoperative and postoperative DVT prevalences were 8.0% (8/100) and 6.6% (6/91), respectively, and none of the patients developed PE. Before surgery, there was no significant differences in D-dimer levels between the pre-DVT (+) and pre-DVT (-) groups. After surgery, the D-dimer level one-day postoperatively for the post-DVT (+) group (17.6 ± 11.8 mg/L) was significantly higher than that of the post-DVT (-) group (5.0 ± 4.7 mg/L). The cutoff value of the postoperative D-dimer level was 9.51(mg/L), and the sensitivity and specificity for the optimum threshold were 83.3% and 89.4%, respectively. Conclusions Our findings suggest that preoperative D-dimer level may not be a predictor of DVT. Preoperative ultrasound examinations should be routinely performed in patients with spinal metastases. Postoperative D-dimer levels greater than 9.51(mg/L) are a predictive factor for the early diagnosis of DVT after spine surgery. Trial registration Our study was registered on Chinese Clinical Trial Registry (No.ChiCTR2000029737). Registered 11 February 2020 - Retrospectively registered, https://www.chictr.org.cn/index.aspx.

Abstract For enhancing the accuracy of cargo box position and angle recognition on the conveyor platform, this paper proposes a cargo box attitude detection and adjustment method based on instance segmentation and image processing. This approach involves generating Mask data through target detection of the cargo box using Mask R-CNN. Using image processing algorithms to generate a minimum rectangle according to the Mask data, and the minimum rectangle data is aligned with the Bbox data of Maks R-CNN. The position and angle of the cargo box are detected based on the minimum rectangular data, and the conveyor platform is adjusted to control the cargo box attitude using the Bbox data. Nine attitude acquisition and comparison experiments were conducted on the cargo box using an angle sensor, and the deviation of the method was consistently $$

Abstract Background Tumor heterogeneity presents a formidable challenge in understanding the mechanisms driving tumor progression and metastasis. The heterogeneity of hepatocellular carcinoma (HCC) in cellular level is not clear. Methods Integration analysis of single-cell RNA sequencing data and spatial transcriptomics data was performed. Multiple methods were applied to investigate the subtype of HCC tumor cells. The functional characteristics, translation factors, clinical implications and microenvironment associations of different subtypes of tumor cells were analyzed. The interaction of subtype and fibroblasts were analyzed. Results We established a heterogeneity landscape of HCC malignant cells by integrated 52 single-cell RNA sequencing data and 5 spatial transcriptomics data. We identified three subtypes in tumor cells, including ARG1+ metabolism subtype (Metab-subtype), TOP2A+ proliferation phenotype (Prol-phenotype), and S100A6+ pro-metastatic subtype (EMT-subtype). Enrichment analysis found that the three subtypes harbored different features, that is metabolism, proliferating, and epithelial-mesenchymal transition. Trajectory analysis revealed that both Metab-subtype and EMT-subtype originated from the Prol-phenotype. Translation factor analysis found that EMT-subtype showed exclusive activation of SMAD3 and TGF-β signaling pathway. HCC dominated by EMT-subtype cells harbored an unfavorable prognosis and a deserted microenvironment. We uncovered a positive loop between tumor cells and fibroblasts mediated by SPP1-CD44 and CCN2/TGF-β-TGFBR1 interaction pairs. Inhibiting CCN2 disrupted the loop, mitigated the transformation to EMT-subtype, and suppressed metastasis. Conclusion By establishing a heterogeneity landscape of malignant cells, we identified a three-subtype classification in HCC. Among them, S100A6+ tumor cells play a crucial role in metastasis. Targeting the feedback loop between tumor cells and fibroblasts is a promising anti-metastatic strategy.

Porous ceramics usually require high mechanical strength and maximized porosity simultaneously, while for conventional particle grading strategies, it is highly challenging to meet both demands. To this end, a reverse particle grading strategy was developed based on the linear packing model by unusually introducing coarse particles (d50 = 16 μm) into a fine particle (d50 = 5 μm) matrix. Following the extrusion and sintering process, tubular porous SiC ceramic supports with improved mechanical strength were successfully fabricated. The effects of coarse particles on the rheological properties of the ceramic paste and the macroscopic properties and microstructure of the SiC supports were systematically investigated. With an increase in the content of coarse SiC particles to 30 wt%, the pressure generated during extrusion decreased from 5.5±0.2 to 1.3±0.1 MPa. Notably, the bending strength of the tubular supports increased from 36.6±5.6 to 49.1±4.5 MPa when 20 wt% coarse powder was incorporated. The notably improved mechanical strength was attributed to the distribution of coarse particles that prolonged the route of crack deflection. Additionally, the optimized tubular supports had an average pore size of 1.2±0.1 μm, an open porosity of 45.1%±1.6%, and a water permeability of 7163±150 L/(m2·h·bar) as well as good alkali and acid corrosion resistance. Significantly, the strategy was proven to be feasible for the scale-up fabrication of 19-channel SiC tubular porous ceramic supports.

Abstract Under subarachnoid hemorrhage (SAH) conditions, astrocytes undergo a marked intensification of glycolytic activity, resulting in the generation of substantial amounts of lactate to maintain the energy demand for neurons and other brain cells. Lactate has garnered increasing attention in recent years because of its emerging role in critical biological processes such as inflammation regulation and neuroprotection, particularly through its histone lactylation. Bromodomain-containing protein 4 (BRD4) plays a crucial role in maintaining neural development and promoting memory formation in the central nervous system. Nonetheless, the function and regulatory mechanism of BRD4 and histone lactylation in astrocytes following SAH remain elusive. Our findings indicate that BRD4, a crucial epigenetic regulator, plays a definitive role in histone lactylation. Both in vitro and in vivo, these results demonstrated that targeted silencing of BRD4 in astrocytes can significantly reduce H4K8la lactylation, thereby aggravating the A1 polarization of astrocytes and ultimately affecting the recovery of neural function and prognosis in mice after SAH. In summary, BRD4 plays a pivotal role in modulating astrocyte polarization following SAH via histone lactylation. Targeting this mechanism might offer an efficient therapeutic strategy for SAH.

The increasing emergence of the time-series single-cell RNA sequencing (scRNA-seq) data, inferring developmental trajectory by connecting transcriptome similar cell states (i.e., cell types or clusters) has become a major challenge. Most existing computational methods are designed for individual cells and do not take into account the available time series information. We present IDTI based on the Increment of Diversity for Trajectory Inference, which combines time series information and the minimum increment of diversity method to infer cell state trajectory of time-series scRNA-seq data. We apply IDTI to simulated and three real diverse tissue development datasets, and compare it with six other commonly used trajectory inference methods in terms of topology similarity and branching accuracy. The results have shown that the IDTI method accurately constructs the cell state trajectory without the requirement of starting cells. In the performance test, we further demonstrate that IDTI has the advantages of high accuracy and strong robustness.

[Introduction] The gas turbine generator set (GE-PG9351FA) with a DLN2.0 + burner and a designed NOx emission concentration of 50 mg/m3 is used in a gas turbine power plant. During the warm-up periods, the generator set emitted a large amount of yellow smoke, which violates provisions stipulated in the "Emission Standard for Air Pollutants from Thermal Power Plants" (GB 13223—2011) and is complained by the surrounding residents. According to the new emission regulations for environmental protection in Jiangsu, starting from January 1, 2023, the converted NOx emission average throughout the operation period should be less than 30 mg/m3. In order to meet this requirement and reduce the emission of yellow nitrate smoke during start-up, the renovated SCR denitration technology for the flue gas of the HRSG (Heat Recovery Steam Generator) is adopted. Data simulation, deduction, analysis and summarization of various indicators are conducted during the start-up process to refine a reasonable startup operation method. [Method] To validate the feasibility of this method, the power plant conducted multiple peak shaving start-up process operation tests. Based on the actual NOx emission characteristics, adjustments were made to the start-up point, gas turbine load control, and input nodes for the SCR system in the operation method. This process resulted in an optimized operational strategy. [Result] The test results show that by optimizing the SCR denitration system input point, gas turbine start-up point and warm-up load after grid connection, the converted NOx emission average throughout the operation period is less than 30 mg/m3, and the phenomenon of yellow nitrate smoke disappeared. [Conclusion] This strategy is based on the characteristics of NOx and yellow nitrate smoke emission during the gas turbine start-up process. Afterward, through data deduction and numerous experiments for validation, it can provide direct guidance for reducing yellow nitrate smoke emission during the start-up process of similar gas turbines. Additionally, it can serve as an analytical reference for controlling NOx emissions during peak shaving operations in gas turbine power plants.

BackgroundHexavalent chromium [Cr(VI)] exposure can cause structural disruption of intestinal flora and functional impairment. Vitamin C (VC) is one of the essential micronutrients, which plays an important role in promoting the growth of intestinal probiotics, improving the intestinal barrier, and maintaining the homeostasis of intestinal flora. However, the regulatory effect of VC on the intestinal flora disorders caused by Cr(VI) exposure remains to be investigated. ObjectiveTo investigate the effect of VC on intestinal flora disruption in mice due to Cr(VI) exposure. MethodsThirty-two SPF-grade C57BL/6 mice were acclimatized and fed for 3 d and randomly divided into control (Con), VC, potassium dichromate [K2Cr2O7, Cr(VI)], and VC+K2Cr2O7 [VC+Cr(VI)] groups. At 8:00 a.m. on day 4, the Con group (double-distilled water given by gavage and injected intraperitoneally), the VC group (VC given by gavage and double-distilled water injected intraperitoneally), the Cr(VI) group (double-distilled water given by gavage and K2Cr2O7 solution injected intraperitoneally), and the VC+Cr(VI) group (VC given by gavage and K2Cr2O7 solution injected intraperitoneally) were treated. The dose of VC was 200 mg·kg−1, and the dose of K2Cr2O7 was 1.25 mg·kg−1. The mice were treated for 45 consecutive days and then executed, the contents of the colon were sampled in sterile freezing tubes, and three replicates were collected from each group. After labeling, the samples were immediately put into liquid nitrogen for rapid freezing. After all the samples were collected, they were transferred to a -80 ℃ ultra-low temperature refrigerator for storage. Samples of colon contents were analyzed for intestinal flora structure by high-throughput sequencing and bioinformatics software. ResultsThe Cr(VI) exposure resulted in reduced body weight gain values in mice compared to the Con group. Pathological changes occurred in the ileal tissue of mice, with significant inflammatory cell infiltration in the Cr(VI) group and reduced inflammatory cell infiltration in the VC+Cr(VI) group. The number of operational taxonomic units (OTUs) of intestinal flora was altered in the Cr(VI) group of mice. In the α diversity analysis, the mean Sobs index in the Cr(VI) group was 240.333±67.796, the Chao index was 258.173±64.813, and the Ace index was 259.481±66.891, which were significantly lower than those in the Con group (P

Abstract We explore the impact of initial state soft gluon radiations on the azimuthal angle asymmetries in photo-production of hard di-jet via coherent diffraction in ultraperipheral heavy ion collisions, as well as in electron-proton (ep) and electron-nucleus (eA) collisions. The primary production mechanism is identified as the diffractive production of two hard jets, accompanied by a collinear gluon emission along the beam direction. In contrast, the diffractive exclusive di-jet production, where the initial state radiation is absent, is suppressed due to color transparency. Our analysis shows that azimuthal asymmetries, traditionally attributed to final state gluon emissions, are reduced by the presence of initial state radiations. The sensitivity of azimuthal asymmetries to both initial and final state radiations suggests that they could provide novel insights into the mechanisms of di-jet production in diffractive processes.

Abstract Integrating genomics and histology for cancer prognosis demonstrates promise. Here, we develop a multi-classifier system integrating a lncRNA-based classifier, a deep learning whole-slide-image-based classifier, and a clinicopathological classifier to accurately predict post-surgery localized (stage I–III) papillary renal cell carcinoma (pRCC) recurrence. The multi-classifier system demonstrates significantly higher predictive accuracy for recurrence-free survival (RFS) compared to the three single classifiers alone in the training set and in both validation sets (C-index 0.831-0.858 vs. 0.642-0.777, p

Abstract. Background:. Limited information exists regarding the impact of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection on psoriasis patients. The objective of this study was to identify clinical factors associated with the prognosis of psoriasis following SARS-CoV-2 infection. Methods:. A retrospective, multicenter study was conducted between March and May 2023. Univariable and multivariable logistic regression analyses were employed to identify factors associated with coronavirus disease 2019 (COVID-19)-related psoriasis outcomes. The study included 2371 psoriasis patients from 12 clinical centers, with 2049 of them having been infected with SARS-CoV-2. Results:. Among the infected groups, lower exacerbation rates were observed in individuals treated with biologics compared to those receiving traditional systemic or nonsystemic treatments (22.3% [236/1058] vs. 39.8% [92/231] vs. 37.5% [140/373], P

Since the approval of gemtuzumab ozogamicin, an antibody–drug conjugate (ADC) targeting CD33 in 2000, 13 ADC drugs have been approved by the FDA. Although these drugs have clearly improved the survival of patients with various types of advanced cancers, their significant toxicity has compromised their therapeutic benefits. The adverse reactions of ADC drugs are complex and include on-target and off-target toxicities, where the payload drug is a determining factor. Antibody and linker may also affect the degree of toxicity. Combination therapy becomes an important strategy in anticancer treatment because of its increased efficiency, but treatment-related adverse reactions also increase accordingly. This review comprehensively analyzes the toxicity mechanisms of current ADC drugs and proposes various optimization strategies, including but not limited to optimizing linker molecules, upgrading antibody design, and changing drug administration strategies, to improve the overall safety profile of ADC drugs.

Abstract Background The advances in deep learning-based pathological image analysis have invoked tremendous insights into cancer prognostication. Still, lack of interpretability remains a significant barrier to clinical application. Methods We established an integrative prognostic neural network for intrahepatic cholangiocarcinoma (iCCA), towards a comprehensive evaluation of both architectural and fine-grained information from whole-slide images. Then, leveraging on multi-modal data, we conducted extensive interrogative approaches to the models, to extract and visualize the morphological features that most correlated with clinical outcome and underlying molecular alterations. Results The models were developed and optimized on 373 iCCA patients from our center and demonstrated consistent accuracy and robustness on both internal (n = 213) and external (n = 168) cohorts. The occlusion sensitivity map revealed that the distribution of tertiary lymphoid structures, the geometric traits of the invasive margin, the relative composition of tumor parenchyma and stroma, the extent of necrosis, the presence of the disseminated foci, and the tumor-adjacent micro-vessels were the determining architectural features that impacted on prognosis. Quantifiable morphological vector extracted by CellProfiler demonstrated that tumor nuclei from high-risk patients exhibited significant larger size, more distorted shape, with less prominent nuclear envelope and textural contrast. The multi-omics data (n = 187) further revealed key molecular alterations left morphological imprints that could be attended by the network, including glycolysis, hypoxia, apical junction, mTORC1 signaling, and immune infiltration. Conclusions We proposed an interpretable deep-learning framework to gain insights into the biological behavior of iCCA. Most of the significant morphological prognosticators perceived by the network are comprehensible to human minds. Graphical Abstract

Abstract Background Brominated Flame Retardants (BFRs) have attracted widespread concern due to their environmental persistence and potential toxicity. This study aims to examine the association between BFRs exposure and hypertension. Methods We used data from the National Health and Nutrition Examination Survey (NHANES) spanning 2005 to 2016 for the cross-sectional analysis. To evaluate the individual and combined impacts of BFRs exposure on hypertension, we utilized multivariate models, including generalized additive models, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) models. Results 9882 individuals (48% male) aged ≥ 20 were included in the final analysis, of whom 4114 had hypertension. After controlling for potential covariates, higher serum concentrations of PBDE100 (OR: 1.26; 95% CI: 1.01, 1.57) and PBDE153 (OR: 1.50; 95% CI: 1.18, 1.88) were significantly associated with hypertension. A nonlinear relationship between PBDE28 and hypertension was observed (P = 0.03). Moreover, BFRs mixture were positively associated with the prevalence of hypertension in both the WQS (β:1.09; 95% CI: 1.02, 1.17; P = 0.02) and BKMR models. Conclusion Our study suggested that BFRs exposure is positively associated with hypertension in the general population. To confirm this association and elucidate the mechanisms, further research is required.

Abstract Regioselective and enantioselective hydroxylation of propargylic C-H bonds are useful reactions but often lack appropriate catalysts. Here a green and efficient asymmetric hydroxylation of primary and secondary C–H bonds at propargylic positions has been established. A series of optically active propargylic alcohols were prepared with high regio- and enantioselectivity (up to 99% ee) under mild reaction conditions by using P450tol, while the C≡C bonds in the molecule remained unreacted. This protocol provides a green and practical method for constructing enantiomerically chiral propargylic alcohols. In addition, we also demonstrated that the biohydroxylation strategy was able to scaled up to 2.25 mmol scale with the production of chiral propargyl alcohol 2a at a yield of 196 mg with 96% ee, which’s an important synthetic intermediate of antifungal drug Ravuconazole. Graphical Abstract

Abstract Flexible surface acoustic wave technology has garnered significant attention for wearable electronics and sensing applications. However, the mechanical strains induced by random deformation of these flexible SAWs during sensing often significantly alter the specific sensing signals, causing critical issues such as inconsistency of the sensing results on a curved/flexible surface. To address this challenge, we first developed high-performance AlScN piezoelectric film-based flexible SAW sensors, investigated their response characteristics both theoretically and experimentally under various bending strains and UV illumination conditions, and achieved a high UV sensitivity of 1.71 KHz/(mW/cm²). To ensure reliable and consistent UV detection and eliminate the interference of bending strain on SAW sensors, we proposed using key features within the response signals of a single flexible SAW device to establish a regression model based on machine learning algorithms for precise UV detection under dynamic strain disturbances, successfully decoupling the interference of bending strain from target UV detection. The results indicate that under strain interferences from 0 to 1160 με the model based on the extreme gradient boosting algorithm exhibits optimal UV prediction performance. As a demonstration for practical applications, flexible SAW sensors were adhered to four different locations on spacecraft model surfaces, including flat and three curved surfaces with radii of curvature of 14.5, 11.5, and 5.8 cm. These flexible SAW sensors demonstrated high reliability and consistency in terms of UV sensing performance under random bending conditions, with results consistent with those on a flat surface.

Background: Osteomyelitis (OM) is an inflammatory condition of bone characterized by cortical bone devascularization and necrosis. Dysregulation of bone remodelling is triggered by OM. Bone remodelling is precisely coordinated by bone resorption and formation via a reversal phase. However, the cellular and molecular mechanisms underlying bone remodelling failure after osteomyelitis remain elusive. Methods: To elucidate the cellular and molecular mechanism underlying bone healing after osteomyelitis, we employed single-cell RNA sequencing (scRNA-seq) to depict the atlas of human cortical bone in normal, infected and reconstructed states. Dimensionality reduction by t-stochastic neighbourhood embedding (t-SNE) and graph-based clustering were applied to analyse the detailed clusters of osteoclast lineages. After trajectory analysis of osteoclast lineages over pseudotime, real-time PCR and immunofluorescence (IF) staining were applied to identify marker gene expression of various osteoclast lineages in the osteoclast induction model and human bone sections, respectively. The potential function and communication of osteoclasts were analysed via gene set enrichment analysis (GSEA) and CellChat. The chemotactic ability of mesenchymal stem cells (MSCs) and osteoclast lineage cells in various differentiation states was determined by transwell assays and coculture assays. The effects of various osteoclast lineages on the osteogenic differentiation potential of MSCs were also determined by using this coculture system. A normal mouse tibia fracture model and an osteomyelitis-related tibia fracture model were generated via injection of luciferase-labelled Staphylococcus aureus to verify the relationships between a novel osteoclast lineage and MSCs. Then, the infection was detected by a bioluminescence imaging system. Finally, immunofluorescence staining was used to detect the expression of markers of MSCs and novel osteoclast lineages in different remodelling phases in normal and infected bone remodelling models. Results: In this study, we constructed a cell atlas encompassing normal, infected, and reconstructed cortical bone. Then, we identified a novel subset at the earlier stage of the osteoclast lineage that exhibited increased expression of IDO1, CCL3, and CCL4. These IDO1highCCL3highCCL4high cells, termed osteostaticytes (OSCs), were further regarded as the reservoir of osteoclasts in the reversal phase. Notably, OSCs exhibited the highest chemotactic activity, surpassing other lineage subsets. We also discovered that cells at the earlier stage of the osteoclast lineage play a significant role in recruiting mesenchymal stem cells (MSCs). Finally, the data revealed that OSCs might be positively related to the occurrence of bone MSCs and the contribution of bone remodelling. Conclusion: Collectively, our findings revealed a novel stage (OSC) within the osteoclast lineage, potentially representing elusive bone reversal cells due to its increased chemotactic ability towards MSCs and potential contribution to bone remodelling. This study provides valuable insights into the intricate mechanisms of the reversal phase during bone remodelling and unveils potential therapeutic strategies for diseases associated with bone uncoupling. Translational potential of this article: This study identified a new subset, referred to as IDO1(plus symbol) CCL3(plus symbol) CCL4(plus symbol) osteostaticytes which displayed the highest chemotactic activity among all osteoclast lineages and may serve as reversal cells in bone remodelling. These findings offer new insights and insights for understanding bone reversal-related diseases and may serve as novel therapeutic targets for conditions such as osteomyelitis and delayed bone healing.

The synchronized development of mineralized bone and blood vessels is a fundamental requirement for successful bone tissue regeneration. Adequate energy production forms the cornerstone supporting new bone formation. ETS variant 2 (ETV2) has been identified as a transcription factor that promotes energy metabolism reprogramming and facilitates the coordination between osteogenesis and angiogenesis. In vitro molecular experiments have demonstrated that ETV2 enhances osteogenic differentiation of dental pulp stem cells (DPSCs) by regulating the ETV2- prolyl hydroxylase 2 (PHD2)- hypoxia-inducible factor-1α (HIF-1α)- vascular endothelial growth factor A (VEGFA) axis. Notably, ETV2 achieves the rapid reprogramming of energy metabolism by simultaneously accelerating mitochondrial aerobic respiration and glycolysis, thus fulfilling the energy requirements essential to expedite osteogenic differentiation. Furthermore, decreased α-ketoglutarate release from ETV2-modified DPSCs contributes to microcirculation reconstruction. Additionally, we engineered hydroxyapatite/chitosan microspheres (HA/CS MS) with biomimetic nanostructures to facilitate multiple ETV2-DPSC functions and further enhanced the osteogenic differentiation. Animal experiments have validated the synergistic effect of ETV2-modified DPSCs and HA/CS MS in promoting the critical-size bone defect regeneration. In summary, this study offers a novel treatment approach for vascularized bone tissue regeneration that relies on energy metabolism activation and the maintenance of a stable local hypoxia signaling state.

Rockburst is a major challenge to hard rock engineering at great depth. Accurate and timely assessment of rockburst risk can avoid unnecessary casualties and property losses. Despite the existence of various methods for rockburst assessment, there remains an urgent need for a comprehensive and reliable criterion that is easy to both apply and interpret. Developing a new rockburst criterion based on simple parameters can potentially fill this gap. With its advantages, this criterion can facilitate a more effective and efficient prediction of rockburst potential, thereby contributing significantly to enhancing safety measures. In this paper, combined with the internal and external factors of rockburst, four control variables (i.e., integrity index, stress index, brittleness index, and elastic energy index) were selected to be incorporated into a comprehensive rockburstability index (RBSI). Based on 116 sets of rockburst cases, the rockburst potential was accurately quantified and predicted using the categorical boosting (CatBoost) model and the nature-inspired metaheuristic African vultures optimization algorithm (AVOA). In its performance validation, the criterion achieved the highest accuracy of 90.48%, verifying the reliability and effectiveness of the proposed RBSI criterion. Additionally, an interpretive method was applied to analyze the variable influence on the criterion, facilitating the explanation of predictions and the analysis of the formula’s robustness under different conditions. In general, compared with existing criterion methods involving relevant indicators, the newly proposed RBSI criterion enhances the accuracy of rockburst potential prediction, and it can effectively and swiftly evaluate the preliminary risk of rockburst. Lastly, a graphical user interface was developed to provide a clear visualization of the assessment of rockburst potential.

Manual semen evaluation methods are subjective and time-consuming. In this study, a deep learning algorithmic framework was designed to enable non-invasive multidimensional morphological analysis of live sperm in motion, improve current clinical sperm morphology testing methods, and significantly contribute to the advancement of assisted reproductive technologies. We improved the FairMOT tracking algorithm by incorporating the distance and angle of the same sperm head movement in adjacent frames, as well as the head target detection frame IOU value, into the cost function of the Hungarian matching algorithm. For sperm morphology, we used the BlendMask segmentation method to segment individual sperm. SegNet was used to separate the head, midpiece, and principal piece comments from each sperm. Experienced in vivo sperm physicians confirmed a morphological accuracy percentage of 90.82%. A total of 1272 samples were collected from multiple tertiary hospitals for validation of the system, which were also evaluated by physicians. The results of our system were highly consistent with those of manual microscopy. This study realized the automated detection of progressive motility and morphology of sperm simultaneously, which is crucial for selection of morphologically normal and motile sperm for intracytoplasmic sperm injection.

Abstract Lymph node metastasis (LNM) facilitates distant tumor colonization and leads to the high mortality in patients with intrahepatic cholangiocarcinoma (ICC). However, it remains elusive how ICC cells subvert immune surveillance within the primary tumor immune microenvironment (TIME) and subsequently metastasize to lymph nodes (LNs). In this study, scRNA-seq and bulk RNA-seq analyses identified decreased infiltration of dendritic cells (DCs) into primary tumor sites of ICC with LNM, which was further validated via dual-color immunofluorescence staining of 219 surgically resected ICC samples. Tumor-infiltrating DCs correlated with increased CD8+ T cell infiltration and better prognoses in ICC patients. Mechanistically, β-catenin-mediated CXCL12 suppression accounted for the impaired DC recruitment in ICC with LNM. Two mouse ICC cell lines MuCCA1 and mIC-23 cells were established from AKT/NICD or AKT/YAP-induced murine ICCs respectively and were utilized to construct the footpad tumor LNM model. We found that expansion and activation of conventional DCs (cDCs) by combined Flt3L and poly(I:C) (FL-pIC) therapy markedly suppressed the metastasis of mIC-23 cells to popliteal LNs. Moreover, β-catenin inhibition restored the defective DC infiltration into primary tumor sites and reduced the incidence of LNM in ICC. Collectively, our findings identify tumor cell intrinsic β-catenin activation as a key mechanism for subverting DC-mediated anti-tumor immunity in ICC with LNM. FL-pIC therapy or β-catenin inhibitor could merit exploration as a potential regimen for mitigating ICC cell metastasis to LNs and achieving effective tumor immune control.

Abstract Objective Previous resting‐state functional magnetic resonance imaging studies on intracerebral hemorrhage patients have focused more on the static characteristics of brain activity, while the time‐varying effects during scanning have received less attention. Therefore, the current study aimed to explore the dynamic functional network connectivity changes of intracerebral hemorrhage patients. Methods Using independent component analysis, the sliding window approach, and the k‐means clustering analysis method, different dynamic functional network connectivity states were detected from resting‐state functional magnetic resonance imaging data of 37 intracerebral hemorrhage patients and 44 healthy controls. The inter‐group differences in dynamic functional network connectivity patterns and temporal properties were investigated, followed by correlation analyses between clinical scales and abnormal functional indexes. Results Ten resting‐state networks were identified, and the dynamic functional network connectivity matrices were clustered into four different states. The transition numbers were decreased in the intracerebral hemorrhage patients compared with healthy controls, which was associated with trail making test scores in patients. The cerebellar network and executive control network connectivity in State 1 was reduced in patients, and this abnormal dynamic functional connectivity was positively correlated with the animal fluency test scores of patients. Interpretation The current study demonstrated the characteristics of dynamic functional network connectivity in intracerebral hemorrhage patients and revealed that abnormal temporal properties and functional connectivity may be related to the performance of different cognitive domains after ictus. These results may provide new insights into exploring the neurocognitive mechanisms of intracerebral hemorrhage.

Abstract Interactions between osteolineage cells and myeloid cells play important roles in maintaining skeletal homeostasis. Herein, we find that osteolineage cells transfer mitochondria to myeloid cells. Impairment of the transfer of mitochondria by deleting MIRO1 in osteolineage cells leads to increased myeloid cell commitment toward osteoclastic lineage cells and promotes bone resorption. In detail, impaired mitochondrial transfer from osteolineage cells alters glutathione metabolism and protects osteoclastic lineage cells from ferroptosis, thus promoting osteoclast activities. Furthermore, mitochondrial transfer from osteolineage cells to myeloid cells is involved in the regulation of glucocorticoid-induced osteoporosis, and glutathione depletion alleviates the progression of glucocorticoid-induced osteoporosis. These findings reveal an unappreciated mechanism underlying the interaction between osteolineage cells and myeloid cells to regulate skeletal metabolic homeostasis and provide insights into glucocorticoid-induced osteoporosis progression.

Abstract Tetraparvovirus is an emerging parvovirus infecting a variety of mammals and humans, and associated with human diseases including severe acute respiratory infection and acute encephalitis syndrome. In the present study, a Tetraparvovirus ungulate 1 (formerly known as bovine hokovirus) strain HNU-CBY-2023 was identified and characterized from diseased Chinese Simmental from Hunan province, China. The nearly complete genome of HNU-CBY-2023 is 5346 nt in size and showed genomic identities of 85-95.5% to the known Tetraparvovirus ungulate 1 strains from GenBank, indicating a rather genetic variation. Phylogenetic and genetic divergence analyses indicated that Tetraparvovirus ungulate 1 could be divided into two genotypes (I and II), and HNU-CBY-2023 was clustered into genotype II. This study, for the first time, identified Tetraparvovirus ungulate 1 from domestic cattle from mainland China, which will be helpful to understand the prevalence and genetic diversity of Tetraparvovirus ungulate 1.

The nucleocapsid protein (NP) plays a crucial role in SARS-CoV-2 replication and is the most abundant structural protein with a long half-life. Despite its vital role in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) assembly and host inflammatory response, it remains an unexplored target for drug development. In this study, we identified a small-molecule compound (ciclopirox) that promotes NP degradation using an FDA-approved library and a drug-screening cell model. Ciclopirox significantly inhibited SARS-CoV-2 replication both in vitro and in vivo by inducing NP degradation. Ciclopirox induced abnormal NP aggregation through indirect interaction, leading to the formation of condensates with higher viscosity and lower mobility. These condensates were subsequently degraded via the autophagy-lysosomal pathway, ultimately resulting in a shortened NP half-life and reduced NP expression. Our results suggest that NP is a potential drug target, and that ciclopirox holds substantial promise for further development to combat SARS-CoV-2 replication.

Hot compression experiment was conducted on Gleeble-3800 thermal simulation testing machine to investigate the hot deformation behavior of Cr5 die casting mold steel, with deformation temperatures of 1100–1300 °C and strain rates of 0.01−10s−1. The experimental results indicated that deformation temperature and strain rate have significant impacts on dynamic recrystallization(DRX) of Cr5 die casting mold steel, the critical strain of DRX decreased as deformation temperature increased and strain rate decreased. According to the Arrhenius model, the activation energy for deformation was 427.85 kJ/mol, and the constitutive equation of hot deformation was derived. Validation of high temperature flow stress model showed that the fitted model emerged appreciable accuracy and reliability. The processing map was constructed based on DMM theory, which was concluded that the unstable region is mainly concentrated around the deformation condition of 1300 °C/10s−1. Cr5 die casting mold steel exhibits the best hot processing performance under the deformation condition of 1250 °C/0.1s−1, with an excellent efficiency of power dissipation(η = 0.36) and a lower value of Kernel average misorientation(KAM average = 1.675°). Discontinuous dynamic recrystallization (DDRX) is the main mechanism for recrystallization nucleation and growth during hot deformation of Cr5 die casting mold steel.

Abstract Background Gallbladder cancer (GBC) is the most common and lethal malignancy of the biliary tract that lacks effective therapy. In many GBC cases, infiltration into adjacent organs or distant metastasis happened long before the diagnosis, especially the direct liver invasion, which is the most common and unfavorable way of spreading. Methods Single-cell RNA sequencing (scRNA-seq), spatial transcriptomics (ST), proteomics, and multiplexed immunohistochemistry (mIHC) were performed on GBC across multiple tumor stages to characterize the tumor microenvironment (TME), focusing specifically on the preferential enrichment of neutrophils in GBC liver invasion (GBC-LI). Results Multi-model Analysis reveals the immunosuppressive TME of GBC-LI that was characterized by the enrichment of neutrophils at the invasive front. We identified the context-dependent transcriptional states of neutrophils, with the Tumor-Modifying state being associated with oxidized low-density lipoprotein (oxLDL) metabolism. In vitro assays showed that the direct cell-cell contact between GBC cells and neutrophils led to the drastic increase in oxLDL uptake of neutrophils, which was primarily mediated by the elevated OLR1 on neutrophils. The oxLDL-absorbing neutrophils displayed a higher potential to promote tumor invasion while demonstrating lower cancer cytotoxicity. Finally, we identified a neutrophil-promoting niche at the invasive front of GBC-LI that constituted of KRT17+ GBC cells, neutrophils, and surrounding fibroblasts, which may help cultivate the oxLDL-absorbing neutrophils. Conclusions Our study reveals the existence of a subset of pro-tumoral neutrophils with a unique ability to absorb oxLDL via OLR1, a phenomenon induced through cell-cell contact with KRT17+ GBC cells in GBC-LI.

Abstract Land-use change is a direct driver of biodiversity loss, projection and future land use change often consider a topical issue in response to climate change. Yet few studies have projected land-use changes over Africa, owing to large uncertainties. We project changes in land-use and land-use transfer under future climate for three specified time periods: 2021–2040, 2041–2060, and 2081–2100, and compares the performance of various scenarios using observational land-use data for the year 2020 and projected land-use under seven Shared Socioeconomic Pathways Scenarios (SSP): SSP1-1.9, SSP1-2.6, SSP2-4.5, SSP3-7.0, SSP4-3.4, SSP4-6.0 and SSP5-8.5 from 2015 to 2100 in Africa. The observational land-use types for the year 2020 depict a change and show linear relationship between observational and simulated land-use with a strong correlation of 0.89 (P

Abstract Zinc (Zn) is a crucial trace element essential for human growth and development, particularly for reproductive health. Previous research has shown a decrease in serum zinc concentration with age and individuals with conditions such as polycystic ovary syndrome (PCOS) and diabetes mellitus. However, the specific effects of zinc deficiency on the female reproductive system, especially ovarian function, are not fully understood. In our study, we observed a significant reduction in the total number of follicles and mature follicles in the zinc deficiency group. This reduction correlated with decreased level of anti-Mullerian hormone (AMH) and abnormal gene expression affecting hormone secretion regulation. Furthermore, we found that zinc deficiency disrupted mitochondrial dynamics, leading to oxidative stress in the ovaries, which further inhibited autophagy and increased ovarian apoptosis. These changes ultimately resulted in the failure of germinal vesicle breakdown (GVBD) and reduced oocyte quality. Meanwhile, administration of zinc glycine effectively alleviated the oocyte meiotic arrest caused by dietary zinc deficiency. In conclusion, our findings demonstrated that dietary zinc deficiency can affect hormone secretion and follicle maturation by impairing mitochondrial function and autophagy.

Abstract Rockburst, coal bump, and mine earthquake are the most important dynamic disaster phenomena in deep mining. This paper summarizes the differences and connections between rockburst, coal bumps and mine earthquakes in terms of definition, mechanism, phenomenon, evaluation index, etc. The definition and evolution progress of the three disaster categories are summarized, as well as the monitoring, early warning, and prevention measures are also presented. Firstly, by combining theoretical research with specific technologies and engineering field cases, the main categories and failure mechanisms of rockburst, coal bumps and mine earthquakes are introduced. Then, the evaluation indexes of coal bump and mine earthquake are summarized, and a new evaluation index of rockburst is given. Finally, the characteristics of monitoring, early warning technologies and prevention methods of rockburst, coal bumps, and mine earthquakes are discussed in technology and application. At last, the future directions of rockburst, coal bump and mine earthquake are put forward.

Abstract Background Chronic obstructive pulmonary disease (COPD) is a significant global health issue, suspected to elevate the risk for various cancers. This study sought to discern whether COPD serves as a risk marker or a causative factor for prevalent cancers. Methods We employed univariable MR (UVMR) analyses to investigate the causal relationship between COPD and the top ten common cancers. Sensitivity analyses were performed to validate the main findings. Multivariable MR (MVMR) and two-step MR analyses were also conducted. False-discovery-rate (FDR) was used to correct multiple testing bias. Results The UVMR analysis demonstrated notable associations between COPD and lung cancer (odds ratio [OR] = 1.42, 95%CI 1.15–1.77, FDR = 6.37 × 10–3). This relationship extends to lung cancer subtypes such as squamous cell carcinoma (LUSC), adenocarcinoma (LUAD), and small cell lung cancer (SCLC). A tentative link was also identified between COPD and bladder cancer (OR = 1.53, 95%CI 1.03–2.28, FDR = 0.125). No significant associations were found between COPD and other types of cancer. The MVMR analysis that adjusted for smoking, alcohol drinking, and body mass index did not identify any significant causal relationships between COPD and either lung or bladder cancer. However, the two-step MR analysis indicates that COPD mediated 19.2% (95% CI 12.7–26.1%), 36.1% (24.9–33.2%), 35.9% (25.7–34.9%), and 35.5% (26.2–34.8%) of the association between smoking and overall lung cancer, as well as LUAD, LUSC, and SCLC, respectively. Conclusions COPD appears to act more as a risk marker than a direct cause of prevalent cancers. Importantly, it partially mediates the connection between smoking and lung cancer, underscoring its role in lung cancer prevention strategies.

Tobacco stems constitute a large amount of waste biomass generated during tobacco production, and their recycling is of great significance to the environment and the conservation of resources. In this study, an efficient, inexpensive, and less toxic strategy is reported for recycling waste tobacco stem, wherein the spherical tobacco stem nanocellulose (STsN) with a size of 10 to 100 nm was prepared from waste stems using a NaOH/urea/thiourea aqueous system. The morphology of STsN was characterized using scanning electron microscopy. The crystal structure of STsN was determined using X-ray diffractometry. The nanocellulose exhibited the crystal structure of cellulose II. Fourier-transform infrared spectra of the STsN indicated that STsN retained the typical chemical structure of cellulose. The thermal properties of STsN were investigated by thermogravimetry. It is concluded that the STsN had better thermal stability than cellulose. The product has potential for practical application with high thermal stability requirements, such as transistors and batteries.

Abstract Carbon dots (CDs) are novel carbon-based nanomaterials that have been used as photosensitizer-mediated photodynamic therapy (PDT) in recent years due to their good photosensitizing activity. Photosensitizers (PSs) are main components of PDT that can produce large amounts of reactive oxygen species (ROS) when stimulated by light source, which have the advantages of low drug resistance and high therapeutic efficiency. CDs can generate ROS efficiently under irradiation and therefore have been extensively studied in disease local phototherapy. In tumor therapy, CDs can be used as PSs or PS carriers to participate in PDT and play an extremely important role. In bacterial infectious diseases, CDs exhibit high bactericidal activity as CDs are effective in disrupting bacterial cell membranes leading to bacterial death upon photoactivation. We focus on recent advances in the therapy of cancer and bacteria with CDs, and also briefly summarize the mechanisms and requirements for PSs in PDT of cancer, bacteria and other diseases. We also discuss the role CDs play in combination therapy and the potential for future applications against other pathogens. Graphical Abstract

Abstract Background Hepatocellular carcinoma (HCC) ranks as the third most common cause of cancer related death globally, representing a substantial challenge to global healthcare systems. In China, the primary risk factor for HCC is the hepatitis B virus (HBV). Aberrant serum glycoconjugate levels have long been linked to the progression of HBV-associated HCC (HBV-HCC). Nevertheless, few study systematically explored the dysregulation of glycoconjugates in the progression of HBV-associated HCC and their potency as the diagnostic and prognostic biomarker. Methods An integrated strategy that combined transcriptomics, glycomics, and glycoproteomics was employed to comprehensively investigate the dynamic alterations in glyco-genes, N-glycans, and glycoproteins in the progression of HBV- HCC. Results Bioinformatic analysis of Gene Expression Omnibus (GEO) datasets uncovered dysregulation of fucosyltransferases (FUTs) in liver tissues from HCC patients compared to adjacent tissues. Glycomic analysis indicated an elevated level of fucosylated N-glycans, especially a progressive increase in fucosylation levels on IgA1 and IgG2 determined by glycoproteomic analysis. Conclusions The findings indicate that the abnormal fucosylation plays a pivotal role in the progression of HBV-HCC. Systematic and integrative multi-omic analysis is anticipated to facilitate the discovery of aberrant glycoconjugates in tumor progression.