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The stratigraphic correlation of well logs plays an essential role in characterizing subsurface reservoirs. However, it suffers from a small amount of training data and expensive computing time. In this work, we propose the Attention Based Dense Network (ASDNet) for the stratigraphic correlation of well logs. To implement the suggested model, we first employ the attention mechanism to the input well logs, which can effectively generate the weighted well logs to serve for further feature extraction. Subsequently, the DenseNet is utilized to achieve good feature reuse and avoid gradient vanishing. After model training, we employ the ASDNet to the testing data set and evaluate its performance based on the well log data set from Northwest China. Finally, the numerical results demonstrate that the suggested ASDNet provides higher prediction accuracy for automated stratigraphic correlation of well logs than state-of-the-art contrastive UNet and SegNet.

Wetlands provide vital ecological services for both humans and environment, necessitating continuous, refined and up-to-date mapping of wetlands for conservation and management. In this study, we developed an automated and refined wetland mapping framework integrating training sample migration method, supervised machine learning and knowledge-driven rules using Google Earth Engine (GEE) platform and open-source geospatial tools. We applied the framework to temporally dense Sentinel-1/2 imagery to produce annual refined wetland maps of the Dongting Lake Wetland (DLW) during 2015–2021. First, the continuous change detection (CCD) algorithm was utilized to migrate stable training samples. Then, annual 10 m preliminary land cover maps with 9 classes were produced using random forest algorithm and migrated samples. Ultimately, annual 10 m refined wetland maps were generated based on preliminary land cover maps via knowledge-driven rules from geometric features and available water-related inventories, with Overall Accuracy (OA) ranging from 81.82% (2015) to 93.84% (2020) and Kappa Coefficient (KC) between 0.73 (2015) and 0.91 (2020), demonstrating satisfactory performance and substantial potential for accurate, timely and type-refined wetland mapping. Our methodological framework allows rapid and accurate monitoring of wetland dynamics and could provide valuable information and methodological support for monitoring, conservation and sustainable development of wetland ecosystem.

Protecting the skin from UV light irradiation in wet and underwater environments is challenging due to the weak adhesion of existing sunscreen materials but highly desired. Herein we report a polyethyleneimine/thioctic acid/titanium dioxide (PEI/TA/TiO2) coacervate-derived hydrogel with robust, asymmetric, and reversible wet bioadhesion and effective UV-light-shielding ability. The PEI/TA/TiO2 complex coacervate can be easily obtained by mixing a PEI solution and TA/TiO2 powder. The fluid PEI/TA/TiO2 coacervate deposited on wet skin can spread into surface irregularities and subsequently transform into a hydrogel with increased cohesion, thereby establishing interdigitated contact and adhesion between the bottom surface and skin. Meanwhile, the functional groups between the skin and hydrogel can form physical interactions to further enhance bioadhesion, whereas the limited movement of amine and carboxyl groups on the top hydrogel surface leads to low adhesion. Therefore, the coacervate-derived hydrogel exhibits asymmetric adhesiveness on the bottom and top surfaces. Moreover, the PEI/TA/TiO2 hydrogel formed on the skin could be easily removed using a NaHCO3 aqueous solution without inflicting damage. More importantly, the PEI/TA/TiO2 hydrogel can function as an effective sunscreen to block UV light and prevent UV-induced MMP-9 overexpression, inflammation, and DNA damage in animal skin. The advantages of PEI/TA/TiO2 coacervate-derived hydrogels include robust, asymmetric, and reversible wet bioadhesion, effective UV light-shielding ability, excellent biocompatibility, and easy preparation and usage, making them a promising bioadhesive to protect the skin from UV light-associated damage in wet and underwater environments.

Abstract Infrared small target detection is widely applied in military and civilian fields. Due to the small size of infrared targets, textural detail is missing. Common target detection methods extract semantic feature by narrowing down the feature map several times, which may lead to the small targets lost in deep layers and are not effective for infrared small target detection. To solve this problem, we propose a novel network called deep asymmetric extraction and aggregation. The network mainly consists of two processes - the vertical feature extraction and the horizontal feature aggregation, both of which are enhanced by an asymmetric attention mechanism. In the vertical process, the use of asymmetric attention mechanism combined with the reduction of down-sampling makes the small target better retained in the deep layers. Then through the horizontal process, shallow spatial feature and deep semantic feature are aggregated to further highlight the small targets while suppressing background noise. Experiments on the public datasets NUAA-SISRT, NUDT-SISRT and MDvsFA-cGan show that our proposed network outperforms the state-of-the-art methods in terms of detection accuracy and parameter efficiency.

Abstract The breach risk of reservoir dam exists objectively while exerting benefits. There is great uncertainty in the overtopping breach process of embankment dam and the dam break flood routing which affects the accuracy of dam risk analysis and may cause unnecessary waste in emergency scheduling. However, the uncertainty analysis of the breach process and its consequence is currently inadequate. Therefore, a stratified sampling Monte Carlo method is proposed to simulate uncertain overtopping breach flood of embankment dams. The main sources of uncertainty are analyzed and determined as uncertain dam breach and flood routing processes. The uncertain breach process of dam is studied by presenting a sensitive study between 3 mechanism breach models and 5 parametric breach models. The random dam breach process is restored using HEC-RAS semi-empirical breach model by estimating breach characteristics through multiple common breach models. The random flood routing is carried out through 1D–2D coupled unsteady flow analysis in which the random breach process is adopted as an upper inflow boundary condition. According to the case study results, though parameters have been controlled in a limited range, the flood routing results in the early stage of dam overtopping failure present greater uncertainty. As the flood progresses further downstream, the uncertainty will gradually decrease. This study could serve as a reference for dam breach risk map making.

Abstract Fusarium head blight (FHB) caused by Fusarium species, seriously threatens the safety of wheat (Triticum aestivum) production. Resistant cultivars and fungicides are frequently used to control these FHB pathogens. However, Fusarium species have been adapting the current FHB control approaches in a manner that raises concern for future FHB control strategies, which could lead to a greater risk of FHB outbreaks. In this study, a total of 521 strains of Fusarium were isolated from Sichuan province of China, to investigate the diversity of Fusarium species and the genes associated with their adaptation. Seven species were identified based on molecular markers and morphological analysis. The virulence assays showed that Fusarium asiaticum (Fa) and Fusarium graminearum (Fg) were the two major causal agents of FHB, with high virulence and more frequent isolates. Fungicide resistance analysis showed that four isolates had developed the resistance to carbendazim, and four isolates had developed the resistance to tebuconazole. Of note, two point-mutation variants (F200Y and E198Q) occurred in the β2-tubulin gene, leading to the carbendazim resistance. The landscape of genomic diversity was analyzed through whole-genome sequencing, revealing a total of 182,811 and 430,733 variants (including: single nucleotide polymorphisms, SNP, insertion and deletion, Indel, and structure variation, SV) among the Fa and Fg isolates, respectively. In addition, potential alterations in gene function (15.22%) were predicted among Fg variants. These alterations offer potential helps for the Fusarium species to adapt to various managements of FHB, which may increase risks in developing fungicide-resistant isolates. However, these annotated genetic variants are valuable resources for further genetic and genomic studies, as well as potential markers to assist disease risk assessment.

Abstract Background The prevalence of childhood obesity and overweight has risen globally, leading to increased rates of metabolic disorders. Various factors, including genetic, epigenetic, and environmental influences such as diet and physical activity, contribute to pediatric obesity. This study aimed to identify specific circulating miRNAs as potential biomarkers for assessing obesity in children. Methods Thirty children, including 15 obese and 15 extremely thin individuals, were selected for this study. MiRNA expression in circulating plasma was assessed using miRNA microarrays. The reliability of differential miRNA expression was confirmed using TaqMan qPCR. The correlation between miRNAs and obesity was analyzed through multiple linear regression, receiver operator characteristic (ROC) curve analysis, and odds ratio (OR) calculations. Bioinformatics tools were utilized to identify target genes for the selected miRNAs, and a functional network map was constructed. Results A total of 36 differentially expressed miRNAs were identified through gene chip analysis, and TaqMan qPCR validation confirmed the upregulation of seven miRNAs: hsa-miR-126-3p, hsa-miR-15b-5p, hsa-miR-199a-3p, hsa-miR-20a-5p, hsa-miR-223-3p, hsa-miR-23a-3p, and hsa-miR-24-3p. Among these, hsa-miR-15b-5p and hsa-miR-223-3p exhibited a statistically significant difference except for hsa-miR-23a-3p. These two miRNAs showed more predicted target genes related to obesity than others. Multiple linear regression analysis revealed an association between obesity and hsa-miR-15b-5p and hsa-miR-223-3p [10.529 (4.974–16.084), -10.225 (-17.852~ -2.657)]. Even after adjusting for age and sex, these two miRNAs remained associated with obesity [8.936 (3.572–14.301), -8.449(-15.634~ -1.303)]. The area under the ROC curve (AUC) reached values of 0.816, 0.711, and 0.929, respectively. Odds ratio analysis demonstrated a significant correlation between obesity and hsa-miR-15b-5p (OR = 143, 95% CI 5.80 to 56,313, p = 0.024) and between obesity and hsa-miR-223-3p (OR = 0.01, 95% CI 0.00 to 0.23, p = 0.037). Importantly, hsa-miR-15b-5p was found to have numerous target genes associated with the FoxO, insulin, Ras, and AMPK signaling pathways. Conclusions Differential miRNA expression profiles in the circulation of obese children compared to controls suggest underlying metabolic abnormalities. Hsa-miR-15b-5p and hsa-miR-223-3p may be considered as molecular markers for the screening of obese children and populations at risk of developing metabolic syndrome.

BackgroundCompared with adult-onset schizophrenia， patients with adolescent-onset schizophrenia experience a high genetic susceptibility， severe negative symptoms， high recurrence rate， poor prognosis and social function recovery. And clarifying the brain functional alterations in adolescent-onset schizophrenia is of great significance for further elucidating the pathogenesis of the disease and exploring personalized and precise treatment.ObjectiveTo investigate the altered functional and effective connectivity of bilateral precuneus in first-episode patients with adolescent-onset schizophrenia based on resting-state functional magnetic resonance imaging （rs-fMRI）， thus providing reliable imaging evidence in guiding the study on mechanism involved in adolescent-onset schizophrenia.MethodsTwenty-one drugnaïve first-episode patients with adolescent-onset schizophrenia who met the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） criteria for schizophrenia were enrolled， and another 21 psychiatrially healthy controls matched on age， educational background and gender were concurrently selected. The schizophrenic subjects were evaluated using the Psychotic Symptom Rating Scales （PSYRATS） and Positive and Negative Symptom Scale （PANSS）. All participants underwent rs-fMRI scans， and the whole-brain seed-based functional and effective connectivity analyses were conducted in bilateral cuneus region. Then the correlation between functional connectivity strength and clinical symptoms of patients was discussed.ResultsIn terms of functional connectivity， the functional connectivity of bilateral precuneus and left middle temporal gyrus was increased in patient group compared with healthy control group ［P

Abstract Zinc finger protein 281 (ZNF281) has been shown to promote tumor progression. However, the underlying mechanism remains to be further elucidated. In this study, ZNF281 knockdown increased the expression of mitochondrial transcription factor A (TFAM) in hepatocellular carcinoma (HCC) cells, accompanied with increment of mitochondrial content, oxygen consumption rate (OCR) and levels of TCA cycle intermetabolites. Mechanistic investigation revealed that ZNF281 suppressed the transcription of TFAM, nuclear respiratory factor 1 (NRF1) and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α). Furthermore, ZNF281 interacted with NRF1 and PGC-1α, and was recruited onto the promoter regions of TFAM, TFB1M and TFB2M repressing their expression. Knockdown of TFAM reversed ZNF281 depletion induced up-regulation of mitochondrial biogenesis and function, as well as impaired epithelial mesenchymal transition, invasion and metastasis of HCC cells. Our research uncovered a novel suppressive function of ZNF281 on mitochondrial biogenesis through inhibition of the NRF1/PGC-1α-TFAM axis, which may hold therapeutic potentials for HCC.

Abstract Purpose To predict the tertiary lymphoid structures (TLSs) status and recurrence-free survival (RFS) of intrahepatic cholangiocarcinoma (ICC) patients using preoperative CT radiomics. Patients and methods A total of 116 ICC patients were included (training: 86; external validation: 30). The enhanced CT images were performed for the radiomics model. The logistic regression analysis was applied for the clinical model. The combined model was based on the clinical and radiomics models. Results A total of 107 radiomics features were extracted, and after being eliminated and selected, six features were combined to establish a radiomics model for TLSs prediction. Arterial phase diffuse hyperenhancement and AJCC 8th stage were combined to construct a clinical model. The combined (radiomics nomogram) model outperformed both the independent radiomics model and clinical model in the training cohort (AUC, 0.85 vs. 0.82 and 0.75, respectively) and was validated in the external validation cohort (AUC, 0.88 vs. 0.86 and 0.71, respectively). Patients in the rad-score no less than −0.76 (low-risk) group showed significantly better RFS than those in the less than −0.76 (high-risk) group (p

Abstract Objective To predict the very early recurrence (VER) of patients with intrahepatic cholangiocarcinoma (ICC) based on TLSs and MVI status, and further perform prognosis stratifications. Methods A total of 160, 51 ICC patients from two institutions between May 2012 and July 2022 were retrospectively included as training, external validation cohort. Clinical, radiological and pathological variables were evaluated and collected. Univariate and multivariate analysis were applied to select the significant factors related to VER of ICC. The factors selected were combined to perform stratification of overall survival (OS) using the Kaplan-Meier method with the log-rank test. Results Overall, 39 patients (24.4%) had VER, whereas 121 (75.6%) did not (non-VER group). In the training cohort, the median OS was 40.5 months (95% CIs: 33.2–47.7 months). The VER group showed significantly worse OS than the non-VER group (median OS: 14.8, 95% CI:11.6–18.0 months vs. 53.4, 34.3–72.6 months; p

Abstract Background Aicardi-Goutières syndrome (AGS) is a rare hereditary early-onset encephalopathy characterized by upregulation of the type I interferon pathway, poorly responsive to conventional immunosuppression. Case presentation We describe a 7-year-old Chinese boy who developed symptoms at the age of 6 months. He presented with a chilblain-like rash, leukopenia, neutropenia, elevated liver enzymesgrowth retardation, microcephaly, elevated acute phase reactants, intracranial calcification and leukodystrophy. At the age of 3 years old, whole-exome sequencing confirmed a de novo heterozygous gain-of-function mutation, c.1016 C > A (p.Ala339Asp), in the IFIH1 gene, and he was diagnosed with AGS7. He was treated with ruxolitinib accompanied by steroids and thalidomide for about four years. The rash, hematological manifestations, and the liver function were all improved, but the erythrocyte sedimentation rate remained consistently elevated until the addition of tocilizumab, a monoclonal antibody against interleukin 6. Conclusions Ruxolitinib was not successful in suppressing the inflammatory process, and tocilizumab produced highly encouraging results in reducing the inflammatory reaction of AGS. The study makes a significant contribution to the literature because we may found a potential alternative therapeutic option for AGS.

Abstract Nemonoxacin is a novel non-fluorinated quinolone with strong antibacterial efficacy, but data of its effect on acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is rare. This study was conducted to compare the efficacy of oral nemonoxacin with moxifloxacin in AECOPD outpatients. In this retrospective observational study, a total of 101 AECOPD outpatients initially treated with nemonoxacin or moxifloxacin from July 2021 to March 2022 were enrolled. We collected COPD assessment test (CAT), Transition Dyspnea Indices (TDI) scores, and exacerbations information during 24 weeks follow-up from the electronic medical records. Kaplan–Meier curve was used to analyze the time to the next moderate/severe exacerbation. Compared to the moxifloxacin group, changes in CAT scores and TDI scores were significantly higher in the nemonoxacin group, and the nemonoxacin group also had a greater probability to reach the minimal clinically important difference of CAT (71.40% vs. 97.80%, p

Herein, we report a ratio-based electrochemical biosensor for the detection of interleukin-6 (IL-6). We electropolymerized methylene blue (MB) on the surface of screen-printed carbon electrodes; introduced an internal reference signal probe; modified the carboxylate multi-walled carbon nanotubes on the electrode surface to increase the electrochemically active area; and finally linked the amino-modified IL-6 aptamer to the electrode surface through the Schiff base reaction, with bovine serum albumin (BSA) added to mask non-specific adsorption. After adding IL-6 to the samples, the signal of IMB remained almost unchanged, while the signal of I[Fe(CN)6]3−/4− decreased with increasing IL-6 concentration. Thus, a novel ratiometric electrochemical sensor with a linear range of 0.001~1000.0 ng/mL and a low detection limit of 0.54 pg/mL was successfully developed. The sensor had high repeatability, stability, sensitivity, and practicability. It provides a new method for constructing proportional electrochemical sensors and detecting IL-6.

(1) Background: This study seeks to employ a machine learning (ML) algorithm to forecast the risk of distant metastasis (DM) in patients with T1 and T2 gallbladder cancer (GBC); (2) Methods: Data of patients diagnosed with T1 and T2 GBC was obtained from SEER, encompassing the period from 2004 to 2015, were utilized to apply seven ML algorithms. These algorithms were appraised by the area under the receiver operating characteristic curve (AUC) and other metrics; (3) Results: This study involved 4371 patients in total. Out of these patients, 764 (17.4%) cases progressed to develop DM. Utilizing a logistic regression (LR) model to identify independent risk factors for DM of gallbladder cancer (GBC). A nomogram has been developed to forecast DM in early T-stage gallbladder cancer patients. Through the evaluation of different models using relevant indicators, it was discovered that Random Forest (RF) exhibited the most outstanding predictive performance; (4) Conclusions: RF has demonstrated high accuracy in predicting DM in gallbladder cancer patients, assisting clinical physicians in enhancing the accuracy of diagnosis. This can be particularly valuable for improving patient outcomes and optimizing treatment strategies. We employ the RF algorithm to construct the corresponding web calculator.

The interaction between protein and water plays a pivotal role in shaping the structure, dynamics, and function of biomacromolecules. A comprehensive understanding of this intricate interplay necessitates a systematic evaluation of interaction strength and its consequential impact on the dynamics of proteins and water across diverse protein systems. Despite numerous works on understanding the dynamics of water and proteins and the coupling between them, there are still unanswered questions. Here, we combine neutron scattering and isotope labeling to probe the dynamics of proteins and their hydration water in a variety of protein systems. We consider proteins of different structures and varying thermostability as well as proteins within living cells with distinct growth temperatures. Simultaneous characterization of protein and hydration water dynamics across diverse systems was achieved. Moreover, we performed water sorption isothermal measurements on three representative proteins to correlate the observed dynamics with the strength of the interaction energies governing each system. The experimental results underscore that proteins manifesting stronger attractive interactions with water display diffusionlike dynamics with higher flexibility upon hydration, concomitant with a reduced mobility in hydration water. Significantly, our findings suggest that, in fact, it is the interaction between protein and its hydration water that facilitates the transfer of mobility from water to protein, with stronger interactions correlating to greater protein flexibility and slower hydration water diffusion.

As the informatization of power systems advances, the secure operation of power systems faces various potential network attacks and threats. The false data injection attack (FDIA) is a common attack mode that can lead to abnormal system operations and serious economic losses by injecting abnormal data into terminal links or devices. The current research on FDIA primarily focuses on detecting its existence, but there is relatively little research on the localization of the attacks. To address this challenge, this study proposes a novel FDIA localization method (GA-CNN-LSTM) that combines convolutional neural networks (CNNs), long short-term memory (LSTM), and a genetic algorithm (GA) and can accurately locate the attacked bus or line. This method utilizes a CNN to extract local features and combines LSTM with time series information to extract global features. It integrates a CNN and LSTM to deeply explore complex patterns and dynamic changes in the data, effectively extract FDIA features in the data, and optimize the hyperparameters of the neural network using the GA to ensure an optimal performance of the model. Simulation experiments were conducted on the IEEE 14-bus and 118-bus test systems. The results indicate that the GA-CNN-LSTM method achieved F1 scores for location identification of 99.71% and 99.10%, respectively, demonstrating superior localization performance compared to other methods.

In order to reduce the influence of environmental noise and different operating conditions on the accuracy of motor fault diagnosis, this paper proposes a capsule network method combining multi-channel signals and the efficient channel attention (ECA) mechanism, sampling the data from multiple sensors and visualizing the one-dimensional time-frequency domain as a two-dimensional symmetric dot pattern (SDP) image, then fusing the multi-channel image data and extracting the image using a capsule network combining the ECA attention mechanism features to match eight different fault types for fault classification. In order to guarantee the universality of the suggested model, data from Case Western Reserve University (CWRU) is used for validation. The suggested multi-channel signal fusion ECA attention capsule network (MSF-ECA-CapsNet) model fault identification accuracy may reach 99.21%, according to the experimental findings, which is higher than the traditional method. Meanwhile, the method of multi-sensor data fusion and the use of the ECA attention mechanism make the diagnosis accuracy much higher.

Blasting excavation of rock masses under high in-situ stress often encounters difficulties in rock fragmentation and a high boulder rate. To gain a deeper understanding of this issue, the stress distribution of rock masses under dynamic and static loads was first studied through theoretical analysis. Then, the ANSYS/LS-DYNA software was employed to simulate the blasting crack propagation in rock masses under various in-situ stress conditions. The fractal dimension was introduced to quantitatively analyze the influence of in-situ stress on the distribution of blasting cracks. The results indicate that in-situ stress primarily affects crack propagation in the later stages of the explosion, while crack initiation and propagation in the early stages are mainly driven by the explosion load. In-situ stress significantly influences the damage area and fractal dimension of cut blasting. Under hydrostatic in-situ stress, as the in-situ stress increases, the damage area and fractal dimension of blasting cracks gradually decrease. Under non-hydrostatic in-situ stress, when the principal stress difference is small, in-situ stress promotes the damage area and fractal dimension of the surrounding rock, enhancing rock fragmentation. However, when the principal stress difference is large, in-situ stress inhibits the damage area and fractal dimension of the surrounding rock, hindering effective rock breaking.

Abstract Background Immune checkpoint inhibitors (ICIs) have emerged as a standard treatment for various malignancies. However, research indicates blocking the immune checkpoint pathway may exacerbate atherosclerotic lesions. Objectives We aimed to investigate whether ICI therapy increases the risk of arterial thromboembolic events (ATEs). Methods A retrospective cohort study was conducted on patients with histologically confirmed cancer at our institution between 2018 and 2021, using the propensity score matching method. The primary endpoint was ATEs occurrence, comprising acute coronary syndrome, stroke/transient ischemic attack, and peripheral arterial thromboembolism. Subgroup analyses assessed whether the ICI treatment effect on ATEs varied over time by limiting the maximum follow‐up duration. Logistic regression analysis identified ATE risk factors in ICI‐treated patients. Results Overall, the ICI group (n = 2877) demonstrated an ATEs risk 2.01 times higher than the non‐ICI group (RR, 2.01 [95% CI (1.61–2.51)]; p

Abstract As an efficient molecular engineering approach, on-surface synthesis (OSS) defines a special opportunity to investigate intermolecular coupling at the sub-molecular level and has delivered many appealing polymers. So far, all OSS is based on the lateral covalent bonding of molecular precursors within a single molecular layer; extending OSS from two to three dimensions is yet to be realized. Herein, we address this challenge by cycloaddition between C60 and an aromatic compound. The C60 layer is assembled on the well-defined molecular network, allowing appropriate molecular orbital hybridization. Upon thermal activation, covalent coupling perpendicular to the surface via [4 + 2] cycloaddition between C60 and the phenyl ring of the molecule is realized; the resultant adduct shows frozen orientation and distinct sub-molecular feature at room temperature and further enables lateral covalent bonding via [2 + 2] cycloaddition. This work unlocks an unconventional route for bottom-up precise synthesis of three-dimensional covalently-bonded organic architectures/devices on surfaces.

Abstract Background Tumor budding (TB) and tumor‐infiltrating lymphocyte (TIL) are significant predictive indicators of lymph node metastasis (LNM) and unfavorable prognosis in various tumors. Currently, there is no gold standard for TB and TIL evaluation in esophageal squamous cell carcinoma (ESCC). This study aimed to identify the standard of TB and TIL evaluations and build a predictive model for prognosis among patients with pT1b ESCC. Methods We retrospectively analyzed the prognostic values of TB and TIL in 150 pT1b ESCC cases. Hematoxylin and eosin (H&E) and immunohistochemistry (IHC) of anti‐pan cytokeratin (AE1/AE3) were used to analyze the threshold of TB, and intratumoral TIL and peritumoral TIL (pTIL) were evaluated using the receiver operating characteristic curves (ROC). Results We found that TB in a three‐tiered grading system (low‐TB: 0‐4; middle‐TB: 5–15; high‐TB: ≥16) displayed an excellent prognosis prediction for LNM and survival based on IHC staining using a 20× objective lens. Low pTIL level (≤20%) was a significant indicator of LNM and unfavorable prognosis (p

Abstract Background Previous studies have reported that transcranial focused ultrasound stimulation can significantly decrease the time to emergence from intraperitoneal ketamine-xylazine anaesthesia in rats. However, how transcranial focused ultrasound stimulation modulates neural activity in anaesthetized rats is unclear. Methods In this study, to answer this question, we used low-intensity transcranial ultrasound stimulation (TUS) to stimulate the brain tissue of propofol-anaesthetized mice, recorded local field potentials (LFPs) in the mouse motor cortex and electromyography (EMG) signals from the mouse neck, and analysed the emergence and recovery time, mean absolute power, relative power and entropy of local field potentials. Results We found that the time to emergence from anaesthesia in the TUS group (20.3 ± 1.7 min) was significantly less than that in the Sham group (32 ± 2.6 min). We also found that compared with the Sham group, 20 min after low-intensity TUS during recovery from anaesthesia, (1) the absolute power of local field potentials in mice was significantly reduced in the [1–4 Hz] and [13–30 Hz] frequency bands and significantly increased in the [55–100 Hz], [100–140 Hz] and [140–200 Hz] frequency bands; (2) the relative power of local field potentials in mice was enhanced at [30–45 Hz], [100–140 Hz] and [140–200 Hz] frequency bands; (3) the entropy of local field potentials ([1-200 Hz]) was increased. Conclusion These results demonstrate that low-intensity TUS can effectively modulate neural activities in both awake and anaesthetized mice and has a positive effect on recovery from propofol anaesthesia in mice.

Abstract Objective To evaluate the effect of basal luteinizing hormone (bLH) levels on In Vitro Fertilization/Intra-Cytoplasmic Injections (IVF/ICSI) outcomes in polycystic ovary syndrome (PCOS). Methods A total of 256 PCOS patients who underwent IVF/ICSI treatment in our center from January 2018 to January 2022 were analyzed retrospectively. The patients were based on the third quartile (12.455) of the basal LH value was taken as the cut-off value and was divided into high and low LH group: high LH group (LH ≥ 12.455 IU / L) and low LH group (LH 0.05). However,there were significant differences in basal LH and basal E2 between low LH group and high LH group, and there were significant differences in basal LH between high LH group and OC group (p 0.05). Moreover, the cycle and clinical pregnancy outcomes and the cumulative clinical pregnancy rate and the cumulative live birth rate were not significantly different among the three groups (p > 0.05). LH levels on the day of antagonist addition affected the number of good-quality embryos (B

Abstract Background Primary pulmonary hyalinizing clear cell carcinoma (HCCC) is a low-grade salivary gland-type carcinoma. Until now, 23 cases of pulmonary HCCC have been reported. Case presentation Here, we present a patient with primary pulmonary HCCC along with vocal-cord squamous cell carcinoma (SCC) revealed by biopsy examination. The patient underwent radiotherapy for vocal-cord SCC, followed by right upper lobectomy and lymph node dissection 10 months later. Histology revealed polygonal cells with eosinophilic or clear cytoplasm in the myxoid matrix together with hyaline degeneration. The tumor involved the whole layer of the segmental bronchus and regionally involved the alveolar tissue along with one intrapulmonary lymph node. Targeted RNA sequencing revealed Ewing Sarcoma Breakpoint Region 1 (EWSR1)- activating transcription factor 1 (ATF1) fusion. We analyzed the data on pulmonary malignant tumors between 2000 and 2019 in the Surveillance, Epidemiology, and End Results (SEER) database and reviewed all cases of pulmonary HCCC with EWSR1 fusion by searching PubMed. The results showed that head and neck (HN) adenoid cystic carcinoma (ACC) (47.89%) and HNSCC (22.54%) were the most common carcinomas occurring with pulmonary salivary gland-type malignant tumors. Screening of 24 cases of pulmonary HCCC with EWSR1 fusion revealed that five cases demonstrated lymph node metastases and only two had documented tumor recurrences. HCCC is rare and easily misdiagnosed as SCC, but the treatment regimen differs between pulmonary HCCC and SCC. Conclusions Hence, pulmonary tumors with clear cells must be diagnosed with caution. Next-generation sequencing (NGS) may be useful for diagnosis, especially in cases with a history of squamous cell carcinoma (SCC).

Abstract Lung cancer ranks as one of the top malignancies and the leading cause of cancer death in both males and females in the US. Using a cancer database covering the entire population, this study was to determine the gender disparities in lung cancer incidence during 2001–2019. Cancer patients were obtained from the National Program of Cancer Registries (NPCR) and Surveillance, Epidemiology and End Results (SEER) database. The SEER*Stat software was applied to calculate the age-adjusted incidence rates (AAIR). Temporal changes in lung cancer incidence were analyzed by the Joinpoint software. A total of 4,086,432 patients (53.3% of males) were diagnosed with lung cancer. Among them, 52.1% were 70 years or older, 82.7% non-Hispanic white, 39.7% from the South, and 72.6% non-small cell lung cancer (NSCLC). The AAIR of lung cancer continuously reduced from 91.0 per 100000 to 59.2 in males during the study period, while it increased from 55.0 in 2001 to 56.8 in 2006 in females, then decreased to 48.1 in 2019. The female to male incidence rate ratio of lung cancer continuously increased from 2001 to 2019. Gender disparities were observed among age groups, races, and histological types. In those aged 0–54 years, females had higher overall incidence rates of lung cancer than males in recent years, which was observed in all races (except non-Hispanic black), all regions, and adenocarcinoma and small cell (but not squamous cell). Non-Hispanic black females aged 0–54 years had a faster decline rate than males since 2013. API females demonstrated an increased trend during the study period. Lung cancer incidence continues to decrease with gender disparities among age groups, races, regions, and histological types. Continuous anti-smoking programs plus reduction of related risk factors are necessary to lower lung cancer incidence further.

As a highly specialized shock-absorbing connective tissue, articular cartilage (AC) has very limited self-repair capacity after traumatic injuries, posing a heavy socioeconomic burden. Common clinical therapies for small- to medium-size focal AC defects are well-developed endogenous repair and cell-based strategies, including microfracture, mosaicplasty, autologous chondrocyte implantation (ACI), and matrix-induced ACI (MACI). However, these treatments frequently result in mechanically inferior fibrocartilage, low cost-effectiveness, donor site morbidity, and short-term durability. It prompts an urgent need for innovative approaches to pattern a pro-regenerative microenvironment and yield hyaline-like cartilage with similar biomechanical and biochemical properties as healthy native AC. Acellular regenerative biomaterials can create a favorable local environment for AC repair without causing relevant regulatory and scientific concerns from cell-based treatments. A deeper understanding of the mechanism of endogenous cartilage healing is furthering the (bio)design and application of these scaffolds. Currently, the utilization of regenerative biomaterials to magnify the repairing effect of joint-resident endogenous stem/progenitor cells (ESPCs) presents an evolving improvement for cartilage repair. This review starts by briefly summarizing the current understanding of endogenous AC repair and the vital roles of ESPCs and chemoattractants for cartilage regeneration. Then several intrinsic hurdles for regenerative biomaterials-based AC repair are discussed. The recent advances in novel (bio)design and application regarding regenerative biomaterials with favorable biochemical cues to provide an instructive extracellular microenvironment and to guide the ESPCs (e.g. adhesion, migration, proliferation, differentiation, matrix production, and remodeling) for cartilage repair are summarized. Finally, this review outlines the future directions of engineering the next-generation regenerative biomaterials toward ultimate clinical translation.

Abstract Polycystic ovary syndrome (PCOS) is known as a prevalent but complicated gynecologic disease throughout the reproductive period. Typically, it is characterized by phenotypic manifestations of hyperandrogenism, polycystic ovary morphology, and persistent anovulation. For now, the therapeutic modality of PCOS is still a formidable challenge. Metabolic aberrations and immune challenge of chronic low-grade inflammatory state are significant in PCOS individuals. Recently, interleukin-22 (IL-22) has been shown to be therapeutically effective in immunological dysfunction and metabolic diseases, which suggests a role in the treatment of PCOS. In this review, we outline the potential mechanisms and limitations of IL-22 therapy in PCOS-related metabolic disorders including its regulation of insulin resistance, gut barrier, systemic inflammation, and hepatic steatosis to generate insights into developing novel strategies in clinical practice.

Abstract Background N6A methylation (m6A) is a significant epigenetic modification that critically impacts post-transcriptional regulation and tumor occurrence and development. While previous studies have identified a role for epigenetic regulation in hepatocellular carcinoma (HCC), the potential function of the m6A cluster in Hepatitis B virus (HBV)-related HCC remains unclear. Methods The related information was downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Based on the expression of 20 m6A regulators, we comprehensively evaluated the m6A clusters and systematically explored the correlation between these clusters and immune cell infiltration characteristics of the tumor microenvironment (TME). The patients were divided into low- and high-m6A score groups. Then, the immune cell infiltration, chemokines, and cytokines levels, and drug sensitivity were further explored between the two groups. Results The m6A cluster predicted a better prognosis that was accompanied by increased immune cell infiltration. Using these results, an m6A score was established that could predict overall survival, immune checkpoints, and clinical treatments for patients with HBV-related HCC. This study demonstrated that m6A modifications affected tumorigenesis, TME, and the prognosis of patients with HBV-related HCC. Conclusion A comprehensive assessment of m6A patterns could improve the current understanding of immune cell infiltration patterns and inform the development of individualized cancer treatments.

Abstract Background To explore the effect of intervention programs constructed under the guidance of the comprehensive unit-based safety program (CUSP) model on chemotherapy-induced nausea and vomiting (CINV) in patients with ovarian cancer. Method According to the time of admission, 90 ovarian cancer chemotherapy patients in the first affiliated Hospital of Anhui Medical University from June 2019 to September 2020 were divided into an intervention group and a control group with 45 cases each. Both groups of patients received routine intervention, and the intervention group implemented the CUSP program on this basis. The intervention lasted 8 months. Before and after the intervention, the patients in the ward were used the Multinational Association of Supportive Care in Cancer (MASCC) Antiemesis Tool, the Functional Living Index-Emesis (FLIE), and the Hospital Anxiety and Depression Scale (HADS) for the effect evaluation. Results After the intervention, the degree of nausea and vomiting frequency in the intervention group were significantly lower than that in the control group, especially the degree of nausea in the delayed phase (P

Abstract Background A one-off sensory wellbeing workshop has been developed to help patients with eating disorders (ED) manage sensory sensitivities. The aim of this study was to evaluate and compare the outcomes of the workshop in online versus face-to-face (F2F) formats among a sample of patients with ED. Methods Cumulative link models were applied to the outcome measures (awareness of sensory wellbeing, awareness of strategies to enhance sensory wellbeing, and confidence in managing sensory wellbeing) to test the differences between online and F2F workshops. Participants’ ratings of usefulness of the workshop were also compared between online and F2F workshops. Results A total of 14 workshops (4 online and 10 F2F) were run from 2020 to 2023. All participants reported significant and substantial improvements in all outcome measures. There was no significant difference in outcomes between online and F2F workshops. The majority of patients rated the workshops as useful. Conclusions Both online and face-to-face formats of the sensory workshop led to improvement in sensory wellbeing management for patients with ED. Future studies are warranted to test the impact of the workshop on ED treatment outcomes.

Introduction One of the ultimate goals of strengthening the health system is to achieve health equity. Vietnam is considered one of the ‘fast-track countries’ to achieve the health-related Millennium Development Goals, but research on its equity strategies remains inadequate.Methods Using Vietnamese official health statistics, we investigated inequity in four dimensions including health resources, service delivery, service utilisation and residents’ health status from the perspectives of income levels, poverty rates and subnational regions. The Slope Index of Inequality, concentration curve/Concentration Index, absolute difference and Theil Index were used.Results Four indicators showed ‘pro-poor’ inequality in health resources, including the per capita health budget, per capita health personnel, per capita health personnel at the community level and per capita hospital beds at the community level, while provincial hospital beds showed ‘pro-rich’ inequality. Two health service delivery indicators (delivery of antenatal care ≥3 times and proportion of community health service centres with medical doctors) show ‘pro-rich’ inequality, although two health status indicators, mortality and malnutrition rates for children under five, showed ‘pro-poor’ inequality. The Northern Midlands and Mountain Areas, and the Central Highlands were disadvantaged regarding service delivery and health status. Intraregional differences were the main factors contributing to the inequalities in delivery of antenatal care ≥3 times, provincial hospital beds and percentage of community health centres with medical doctors, with the Red River Delta and the South East region experiencing the greatest inequalities.Conclusion The overall level of health equity in Vietnam has increased over the past decade, although inequality in health service delivery has hindered progress towards health equity based on income, poverty and subnational regions. Targeted policies need to be introduced to reduce inequities relating to the health workforce and service delivery capacity.

Summary: Stephania japonica is an early-diverging eudicotyledon plant with high levels of cepharanthine, proven to be effective in curing coronavirus infections. Here, we report a high-quality S. japonica genome. The genome size is 688.52 Mb, and 97.37% sequences anchor to 11 chromosomes. The genome comprises 67.46% repetitive sequences and 21,036 genes. It is closely related to two Ranunculaceae species, which diverged from their common ancestor 55.90–71.02 million years ago (Mya) with a whole-genome duplication 85.59–96.75 Mya. We further reconstruct ancestral karyotype of Ranunculales. Several cepharanthine biosynthesis genes are identified and verified by western blot. Two genes (Sja03G0243 and Sja03G0241) exhibit catalytic activity as shown by liquid chromatography-mass spectrometry. Then, cepharanthine biosynthesis genes, transcription factors, and CYP450 family genes are used to construct a comprehensive network. Finally, we construct an early-diverging eudicotyledonous genome resources (EEGR) database. As the first genome of the Menispermaceae family to be released, this study provides rich resources for genomic studies.

As emerging pollutants, antibiotics were widely detected in water bodies and dietary sources. Recently, their obesogenic effects raised serious concerns. So far, it remained unclear whether their obesogenic effects would be influenced by water- and diet-borne exposure routes. In present study, Caenorhabditis elegans, nematodes free-living in air–water interface and feeding on bacteria, were exposed to water- and diet-borne erythromycin antibiotic (ERY). The statuses of the bacterial food, inactivated or alive, were also considered to explore their influences on the effects. Results showed that both water- and diet-borne ERY significantly stimulated body width and triglyceride contents. Moreover, diet-borne ERY’s stimulation on the triglyceride levels was greater with alive bacteria than with inactivated bacteria. Biochemical analysis showed that water-borne ERY inhibited the activities of enzymes like adipose triglyceride lipase (ATGL) in fatty acid β-oxidation. Meanwhile, diet-borne ERY inhibited the activities of acyl-CoA synthetase (ACS) and carnitine palmitoyl transferase (CPT) in lipolysis, while it stimulated the activities of fatty acid synthase (FAS) in lipogenesis. Gene expression analysis demonstrated that water-borne ERY with alive bacteria significantly upregulated the expressions of daf-2, daf-16 and nhr-49, without significant influences in other settings. Further investigation demonstrated that ERY interfered with bacterial colonization in the intestine and the permeability of the intestinal barrier. Moreover, ERY decreased total long-chained fatty acids (LCFAs) in bacteria and nematodes, while it decreased total short-chained fatty acids (SCFAs) in bacteria but increased them in nematodes. Collectively, the present study demonstrated the differences between water- and diet-borne ERY’s obesogenic effects, and highlighted the involvement of insulin and nhr-49 signaling pathways, SCFAs metabolism and also the interaction between intestinal bacteria and the host.

Microplastics (MPs) and pesticides are two categories contaminants with proposed negative impacts to aqueous ecosystems, and adsorption of pesticides on MPs may result in their long-range transport and compound combination effects. Florpyrauxifen-benzyl, a novel pyridine-2-carboxylate auxin herbicide has been widely used to control weeds in paddy field, but the insights of which are extremely limited. Therefore, adsorption and desorption behaviors of florpyrauxifen-benzyl on polyvinyl chloride (PVC), polyethylene (PE) and disposable face masks (DFMs) in five water environment were investigated. The impacts of various environmental factors on adsorption capacity were evaluated, as well as adsorption mechanisms. The results revealed significant variations in adsorption capacity of florpyrauxifen-benzyl on three MPs, with approximately order of DFMs > PE > PVC. The discrepancy can be attributed to differences in structural and physicochemical properties, as evidenced by various characterization analysis. The kinetics and isotherm of florpyrauxifen-benzyl on three MPs were suitable for different models, wherein physical force predominantly governed adsorption process. Thermodynamic analysis revealed that both high and low temperatures weakened PE and DFMs adsorption, whereas temperature exhibited negligible impact on PVC adsorption. The adsorption capacity was significantly influenced by most environmental factors, particularly pH, cations and coexisting herbicide. This study provides valuable insights into the fate of florpyrauxifen-benzyl in presence of MPs, suggesting that PVC, PE and DFMs can serve as carriers of florpyrauxifen-benzyl in aquatic environment.

Abstract Objective This study aimed to explore the clinicopathological characteristics and prognostic implications of gastric neuroendocrine neoplasms (g‐NENs). Methods A retrospective enrollment of 142 patients diagnosed with g‐NENs was conducted at Zhejiang Cancer Hospital between January 1, 2007 and December 31, 2021. The study compared essential clinicopathological features and survival rates. Additionally, the prognosis of gastric neuroendocrine carcinomas/mixed neuroendocrine–non‐neuroendocrine neoplasms (g‐NEC/MiNEN) were contrasted with those of gastric adenocarcinoma (GAC) and signet ring cell carcinoma (SRCC). Results The study comprised a total of 142 g‐NENs cases, with a male‐to‐female ratio of approximately 2:1. The 5‐year survival rates for g‐NEC and g‐MiNEN were 26.7% and 35.2%, respectively. Corresponding 5‐year survival rates for G1 and G2 were observed at 100% and 80.0%, respectively. g‐NEC/MiNEN showed a significantly worse prognosis compared to g‐NET (p

CRISPR/Cas systems have become integral parts of nucleic acid detection apparatus and biosensors. Various CRISPR/Cas systems such as CRISPR/Cas9, CRISPR/Cas12, CRISPR/Cas13, CRISPR/Cas14 and CRISPR/Cas3 utilize different mechanisms to detect or differentiate biological activities and nucleotide sequences. Usually, CRISPR/Cas-based nucleic acid detection systems are combined with polymerase chain reaction, loop-mediated isothermal amplification, recombinase polymerase amplification and transcriptional technologies for effective diagnostics. Premised on these, many CRISPR/Cas-based nucleic acid biosensors have been developed to detect nucleic acids of viral and bacterial pathogens in clinical samples, as well as other applications in life sciences including biosecurity, food safety and environmental assessment. Additionally, CRISPR/Cas-based nucleic acid detection systems have showed better specificity compared with other molecular diagnostic methods. In this review, we give an overview of various CRISPR/Cas-based nucleic acid detection methods and highlight some advances in their development and components. We also discourse some operational challenges as well as advantages and disadvantages of various systems. Finally, important considerations are offered for the improvement of CRISPR/Cas-based nucleic acid testing.

IntroductionForage culture is a common way to restore degraded grasslands and soil functions, in which the reconstruction of the soil microbial community and its relationship with extracellular enzyme activity (EEAs) can characterize the recovery effects of degraded grasslands. However, the impacts of forage culture on the interaction between soil microbes and EEAs and whether the recovery effect of soil functions depends on the varying degradation statuses remain unclear.MethodsWe conducted a plantation of a dominant grass, Leymus chinensis, in the soil collected from severe, moderate, light, and non-degradation statuses in the Songnen grassland in northeastern China. We measured soil microbial diversity and soil EEAs, and predicted microbial functional groups using FUNGuild.ResultsThe results showed that L. chinensis culture promoted soil bacterial alpha diversity and soil EEAs only in the moderate degradation status, indicating a dramatic dependence of the recovery effects of the grass culture on degradation status of the grassland. After planting L. chinensis for 10 weeks, a decreasing trend in the chemoheterotrophy and nitrate-reduction microbial functional groups was found. In contrast, the abundance of the nitrogen (N)-fixing microbial functional group tended to increase. The positive correlation between soil EEAs and the nitrate-reduction and N-fixing microbial functional groups was enhanced by planting L. chinensis, indicating that grass culture could promote soil N cycle functions.ConclusionWe illuminate that grass culture may promote the restoration of soil functions, especially soil N cycling in degraded grasslands, and the recovery effect may depend on the grassland degradation status. We emphasized that selection of the plant species for restoration of grasslands needs to consider the restoration effects of microbial functional groups and soil functions.

Background: The immune response associated with periprosthetic joint infection (PJI) is an emerging but relatively unexplored topic. The aim of this study was to investigate immune cell infiltration in periprosthetic tissues and identify potential immune-related biomarkers. Methods: The GSE7103 dataset from the GEO database was selected as the data source. Differentially expressed genes (DEGs) and significant modular genes in weighted correlation network analysis (WGCNA) were identified. Functional enrichment analysis and transcription factor prediction were performed on the overlapping genes. Next, immune-related genes from the ImmPort database were matched. The protein-protein interaction (PPI) analysis was performed to identify hub genes. CIBERSORTx was used to evaluate the immune cell infiltration pattern. Spearman correlation analysis was used to evaluate the relationship between hub genes and immune cells. Results: A total of 667 DEGs were identified between PJI and control samples, and 1847 PJI-related module genes were obtained in WGCNA. Enrichment analysis revealed that the common genes were mainly enriched in immune and host defense-related terms. TFEC, SPI1, and TWIST2 were the top three transcription factors. Three hub genes, SDC1, MMP9, and IGF1, were identified in the immune-related PPI network. Higher levels of plasma cells, CD4+ memory resting T cells, follicular helper T cells, resting mast cells, and neutrophils were found in the PJI group, while levels of M0 macrophages were lower. Notably, the expression of all three hub genes correlated with the infiltration levels of seven types of immune cells. Conclusion: The present study revealed immune infiltration signatures in the periprosthetic tissues of PJI patients. SDC1, MMP9, and IGF1 were potential immune-related biomarkers for PJI.

Background: Non-alcoholic fatty liver disease (NAFLD) is a prevalent chronic liver condition with significant clinical implications. Emerging research indicates endoplasmic reticulum (ER) stress as a critical pathogenic factor governing inflammatory responses, lipid metabolism and insulin signal transduction in patients with NAFLD. ER stress-associated activation of multiple signal transduction pathways, including the unfolded protein response, disrupts lipid homeostasis and substantially contributes to NAFLD development and progression. Targeting ER stress for liver function enhancement presents an innovative therapeutic strategy. Notably, the natural bioactive compounds of plant extracts have shown potential for treating NAFLD by reducing the level of ER stress marker proteins and mitigating inflammation, stress responses, and de novo lipogenesis. However, owing to limited comprehensive reviews, the effectiveness and pharmacology of these bioactive compounds remain uncertain. Objectives: To address the abovementioned challenges, the current review categorizes the bioactive compounds of plant extracts by chemical structures and properties into flavonoids, phenols, terpenoids, glycosides, lipids and quinones and examines their ameliorative potential for NAFLD under ER stress. Methods: This review systematically analyses the literature on the interactions of bioactive compounds from plant extracts with molecular targets under ER stress, providing a holistic view of NAFLD therapy. Results: Bioactive compounds from plant extracts may improve NAFLD by alleviating ER stress; reducing lipid synthesis, inflammation, oxidative stress and apoptosis and enhancing fatty acid metabolism. This provides a multifaceted approach for treating NAFLD. Conclusion: This review underscores the role of ER stress in NAFLD and the potential of plant bioactive compounds in treating this condition. The molecular mechanisms by which plant bioactive compounds interact with their ER stress targets provide a basis for further exploration in NAFLD management.

Multimodal public transport network (MPTN) plays an important role in relieving road traffic pressure for metropolitan area. Nevertheless, the impact of an accident happened in an individual station may not only disrupt the station itself or the single lines that go through the station but also spread over the whole network. Therefore, identifying the vulnerable stations is essential for improving the MPTN management against the systematic risk caused by accidents. In this paper, we proposed a route diversity-based approach to measure the vulnerability of stations in MPTN based on the complex network theory. The route constraint parameters were established to reflect the travel time restriction in constructing the set of passengers’ acceptable routes. In addition, an algorithm was formulated to rapidly calculate the route diversity index and meanwhile avoid the “overlapping routes” problem. A simple virtual network was used as a numerical example to compare the proposed approach with the vulnerability evaluation approaches based on degree centrality and betweenness centrality. Finally, the proposed approach was applied to the MPTN of Beijing to explain its effectiveness and potential applications. The results show that the proposed method can efficaciously estimate vulnerable nodes compared with degree centrality and betweenness centrality. Meanwhile, the acceptable routes between any OD pairs in the MPTN are 1–10 according to the constrained parameter. In addition, the average number of acceptable routes between OD pairs of Beijing MPTN is 3.649. By ranking the stations according to their vulnerability, it can be found that the top 5 vulnerable stations are all external traffic hubs or the stations around famous commercial areas. The results suggest that these stations are significant for external transport as well as crucial for internal urban transportation systems. The research output could contribute to the MPTN management in accident prevention and emergency handling.

The nearby radio galaxy M87 is a very high-energy (VHE) gamma-ray emitter established by observations with ground-based gamma-ray detectors. Here we report the long-term monitoring of M87 from 2021 to 2024 with the Large High Altitude Air Shower Observatory (LHAASO). M87 has been detected by LHAASO with a statistical significance ∼ 9 σ . The observed energy spectrum extends to 20 TeV, with a possible hardening at ∼20 TeV and then a clear softening at higher energies. Assuming that the intrinsic spectrum is described by a single power law up to 20 TeV, a tight upper bound on the extragalactic background light intensity is obtained. A strong VHE flare lasting 8 days, with a rise time of ${\tau }_{r}^{\mathrm{rise}}=1.05\pm 0.49$ days and decay time of ${\tau }_{d}^{\mathrm{decay}}=2.17\pm 0.58$ days, was found in early 2022. A possible GeV flare is seen also in Fermi Large Area Telescope data during the VHE flare period. The variability time as short as 1 day seen in the LHAASO data suggests a compact emission region with a size of ∼3 × 10 ^15 δ cm ( δ being the Doppler factor of the emitting region), corresponding to a few Schwarzschild radii of the central supermassive black hole in M87. The continuous monitoring of the source reveals a duty cycle of ∼1% for VHE flares with a flux above 10 ^−11 erg cm ^−2 s ^−1 .

The first source catalog of the Large High Altitude Air Shower Observatory (LHAASO) reported the detection of a very high energy gamma-ray source, 1LHAASO J1219+2915. This Letter presents a further detailed study of the spectral and temporal behavior of this pointlike source. The best-fit position of the TeV source (R.A. = 185.°05 ± 0.°04, decl. = 29.°25 ± 0.°03) is compatible with NGC 4278 within ∼0.°03. Variation analysis shows an indication of variability on a timescale of a few months in the TeV band, which is consistent with low-frequency observations. Based on these observations, we report the detection of TeV γ -ray emissions from this low-luminosity active galactic nucleus. The observation by LHAASO's Water Cherenkov Detector Array during the active period has a significance level of 8.8 σ with a best-fit photon spectral index Γ = 2.56 ± 0.14 and a flux f _1–10 TeV = (7.0 ± 1.1 _sta ± 0.35 _syst ) × 10 ^−13 photons cm ^−2 s ^−1 , or approximately 5% of the Crab Nebula. The discovery of VHE gamma-ray emission from NGC 4278 indicates that compact, weak radio jets can efficiently accelerate particles and emit TeV photons.