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Although permeation grouting technology has been widely used in engineering practice, there has not been sufficient research on how the distribution of pore sizes in porous media affects the diffusion of grout. In this study, based on the fractal theory of porous media and the Bingham fluid rheological equation, a Bingham fluid permeation grouting mechanism considering the distribution of pore sizes in porous media is proposed. The mechanism is validated through laboratory experiments and numerical simulations using COMSOL 6.0. During the experiments, parallel electrical resistance imaging is employed to monitor the diffusion range of the grout. Furthermore, the effects of grouting pressure, porosity, and water–cement ratio on the diffusion radius of the grout are analyzed. The results show that the Bingham fluid grout diffuses in a semi-spherical shape in the gravel. Additionally, parallel electrical resistance imaging can analyze the diffusion range of the grout in the gravel. The diffusion radius of the Bingham fluid grout in the gravel is smaller than the diffusion radius obtained by considering the particle size distribution theory, with an average difference of 31.8%. Compared to the diffusion radius obtained without considering the particle size distribution theory, the diffusion radius obtained by considering the distribution of pore sizes is closer to the experimental results. The numerically simulated program, which was developed for this study, can effectively simulate the diffusion law of the Bingham fluid in the gravel. So far, the Bingham fluid seepage grouting model considering the different particle size distribution of porous media has been built. The findings of this study can provide theoretical support and technical reference for practical grouting projects.

For the thick alluvium and thin bedrock coal seam mining in East China, it is easy to produce water by pressing the frame. Taking the engineering geological conditions of the thin bedrock coal seam 1611 (3) working face in the Zhangji Coal Mine of Huainan Mining Group as the research background, the breaking law of the thin bedrock coal seam working face with thick alluvium was studied by using a similar material physical simulation experiment and theoretical analysis. It is revealed that under the load transfer of the loose aquifer, the roof fracture of the stope with thick alluvium and thin bedrock is characterized by large and small periodic ground pressure, and the combination failure of the high key stratum and the low key stratum with large cycles is prone to support crushing accidents. Based on this, the safety mining technical measures of reducing the fracture distance of the high key stratum by forced roof caving are proposed, and the reasonable blasting parameters are calculated. After field application, no support crushing accident on the working face was recorded, and the mining was safe, which provides a technical reference for the mining of the working face under similar conditions.

In view of the occurrence conditions of inclined coalbed, the deformation and failure characteristics of the main roof will affect the safe production of the working face. Therefore, the study of the deformation and failure characteristics of the main roof in the inclined coalbed has guiding significance for the control of surrounding rock. This paper takes the II1042 working face of Taoyuan Coal Mine as the research background, adopts the methods of theoretical analysis, numerical calculation, and field practice to analyze the evolutionary characteristics of the initial failure of the main roof of the working face under the background of the inclined coalbed, and explores the mechanical behavior characteristics of the working face roof during the mining of inclined coalbed. Based on the elastic thin plate theory, a mechanical model of the overlying rock roof of a large-angle coal seam is established, and the mechanical characteristics of the surrounding rock under the initial failure of the main roof under the unbalanced load are studied. The stress distribution characteristics of the lower surface are summarized, and the evolution law of the initial fracture of the main roof is summarized. According to the actual geological conditions of the II1042 working face of Taoyuan Coal Mine, the failure characteristics of the main roof and the initial breaking step distance are obtained by analysis, and the analysis results are verified by monitoring the mine pressure of each part of the target working face on site. The research results show that: ① Under the unbalanced load of the inclined coalbed, the deflection surface of the main roof of the coal seam is asymmetrical with respect to the arrangement direction of the working face, and the maximum deflection point is located at the upper middle position of the working face, namely (a/2, 1.836 b/π), and the main roof of the working face breaks for the first time when it advances to 35 m. ② With the advancement of the working face, the two long sides of the roof break first. With the deflection and deformation of the roof, the tensile stress in the middle of the main roof reaches the tensile strength of the rock and breaks, and then the two short sides of the roof break under the action of the breaking and turning of the rock, and the upper short side will break before the lower one. ③ According to the monitoring and analysis of the rock pressure at each part of the working face, it is judged that the initial pressure step distance is between 28.2 m and 34.6 m, which is consistent with the theoretical analysis results.

Deep learning (DL) has become a powerful tool for the recognition and classification of biological sequences. However, conventional single-architecture models often struggle with suboptimal predictive performance and high computational costs. To address these challenges, we present EnsembleDL-Lipo, an innovative ensemble deep learning framework that combines Convolutional Neural Networks (CNNs) and Deep Neural Networks (DNNs) to enhance the identification of lipocalin sequences. Lipocalins are multifunctional extracellular proteins involved in various diseases and stress responses, and their low sequence similarity and occurrence in the ‘twilight zone’ of sequence alignment present significant hurdles for accurate classification. These challenges necessitate efficient computational methods to complement traditional, labor-intensive experimental approaches. EnsembleDL-Lipo overcomes these issues by leveraging a set of PSSM-based features to train a large ensemble of deep learning models. The framework integrates multiple feature representations derived from position-specific scoring matrices (PSSMs), optimizing classification performance across diverse sequence patterns. The model achieved superior results on the training dataset, with an accuracy (ACC) of 97.65%, recall of 97.10%, Matthews correlation coefficient (MCC) of 0.95, and area under the curve (AUC) of 0.99. Validation on an independent test set further confirmed the robustness of the model, yielding an ACC of 95.79%, recall of 90.48%, MCC of 0.92, and AUC of 0.97. These results demonstrate that EnsembleDL-Lipo is a highly effective and computationally efficient tool for lipocalin sequence identification, significantly outperforming existing methods and offering strong potential for applications in biomarker discovery.

Liquefied natural gas (LNG), an increasingly widely applied clean fuel, releases a large number of cold energy in its regasification process. In the present paper, the existing power generation cycles utilizing LNG cold energy are introduced and summarized. The direction of cycle improvement can be divided into the key factors affecting basic power generation cycles and the structural enhancement of cycles utilizing LNG cold energy. The former includes the effects of LNG-side parameters, working fluids, and inlet and outlet thermodynamic parameters of equipment, while the latter is based on Rankine cycle, Brayton cycle, Kalina cycle and their compound cycles. In the present paper, the diversities of cryogenic power generation cycles utilizing LNG cold energy are discussed and analyzed. It is pointed out that further researches should focus on the selection and component matching of organic mixed working fluids and the combination of process simulation and experimental investigation, etc.

Clinical approaches for cancer therapy face several interrelated challenges involving inefficient drug delivery, potential adverse side effects, and inconvenience. Here, we present an integrated wearable flexible ultrasound microneedle patch (wf-UMP) that serves as a portable platform for convenient, efficient, and minimally invasive cancer therapy. The wf-UMP adopts an all-in-one bioelectronic concept, which integrates a stretchable lead-free ultrasound transducer array for acoustic emission, a bioadhesive hydrogel elastomer for robust adhesion and acoustic coupling, and a dissolvable microneedle patch loaded with biocompatible piezoelectric nanoparticles for painless drug delivery and reactive oxygen species generation. With soft mechanical properties and enhanced electromechanical performance, wf-UMP can be robustly worn on curved and dynamic tissue surfaces for easy and effective manipulation. In preclinical studies involving mice, wf-UMP demonstrated notable anticancer effects by inducing tumor cell apoptosis, amplifying oxidative stress, and modulating immune cell proliferation. Furthermore, the synergistic immunotherapy induced by wf-UMP and Anti-PD1 further improved anticancer immunity by activating immunogenic cell death and regulating macrophages polarization, inhibiting distant tumor growth and tumor recurrence. Clinical approaches for cancer therapy face several interrelated challenges. Here, Xue et al. presented an integrated wearable flexible ultrasound microneedle patch that serves as a portable platform for convenient and minimally invasive cancer therapy.

This study aimed to establish an effective prognostic model based on triglyceride and inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR), to predict overall survival (OS) in patients with nasopharyngeal carcinoma (NPC). Additionally, we aimed to explore the interaction and mediation between these biomarkers in their association with OS. A retrospective review was conducted on 259 NPC patients who had blood lipid markers, including triglyceride and total cholesterol, as well as parameters of peripheral blood cells measured before treatment. These patients were followed up for over 5 years, and randomly divided into a training set (n=155) and a validation set (n=104). The triglyceride-inflammation (TI) score was developed using the random survival forest (RSF) algorithm. Subsequently, a nomogram was created. The performance of the prognostic model was measured by the concordance index (C-index), time-dependent receiver operating characteristic (ROC) curve, and decision curve analysis (DCA). The interaction and mediation between the biomarkers were further analyzed. Bioinformatics analysis based on the GEO dataset was used to investigate the association between triglyceride metabolism and immune cell infiltration. The C-index of the TI score was 0.806 in the training set, 0.759 in the validation set, and 0.808 in the entire set. The area under the curve of time-dependent ROC of TI score in predicting survival at 1, 3, and 5 years were 0.741, 0.847, and 0.871 respectively in the training set, and 0.811, 0.837, and 0.758 in the validation set, then 0.771, 0.848, and 0.862 in the entire set, suggesting that TI score had excellent performance in predicting OS in NPC patients. Patients with stage T1-T2 or M0 had significantly lower TI scores, NLR, and PLR, and higher LMR compared to those with stage T3-T3 or M1, respectively. The nomogram, which integrated age, sex, clinical stage, and TI score, demonstrated good clinical usefulness and predictive ability, as evaluated by the DCA. Significant interactions were found between triglyceride and NLR and platelet, but triglyceride did not exhibit any medicating effects in the inflammatory markers. Additionally, NPC tissues with active triglyceride synthesis exhibited high immune cell infiltration. The TI score based on RSF represents a potential prognostic factor for NPC patients, offering convenience and economic advantages. The interaction between triglyceride and NLR may be attributed to the effect of triglyceride metabolism on immune response.

Regioselective C–H functionalization of pyridines remains a persistent challenge due to their inherent electronically deficient properties. In this report, we present a strategy for the selective pyridine C3-H thiolation, selenylation, and fluorination under mild conditions via classic N −2,4-dinitrophenyl Zincke imine intermediates. Radical inhibition and trapping experiments, as well as DFT theoretical calculations, indicated that the thiolation and selenylation proceeds through a radical addition-elimination pathway, whereas fluorination via a two-electron electrophilic substitution pathway. The pre-installed electron-deficient activating N -DNP group plays a crucial and positive role, with the additional benefit of recyclability. The practicability of this protocol was demonstrated in the gram-scale synthesis and the late-stage modification of pharmaceutically relevant pyridines. Regioselective C–H functionalization of pyridines remains a persistent challenge due to their inherent electronically deficient properties. Here, the authors present a strategy for the selective pyridine C3-H thiolation, selenylation, and fluorination under mild conditions via classic N -2,4-dinitrophenyl Zincke imine intermediates.

Neurotransmitter serotonin (5-hydroxytryptamine [5-HT]) has emerged to play parallel roles in both neurobiology and oncology. Apart from receptor-mediated signaling transduction pattern, serotonin can be covalently integrated into histone (the post-translational modification known as histone serotonylation) and serve as an epigenetic mark associated with permissive gene expression. However, how histone serotonylation influences tumorigenesis is yet to be understood. In this study, we observe the higher levels of histone serotonylation (H3K4me3Q5ser) and transglutaminases 2 (TGM2, the enzyme catalyzing serotonylation) in both pancreatic ductal adenocarcinoma (PDAC) tissues and cell lines in comparison with their normal counterparts, and inhibition of histone serotonylation suppresses PDAC development. Mechanistically, we demonstrate that TGM2-mediated histone serotonylation at promoter of the gene encoding stearoyl-CoA desaturase (SCD) up-regulates its expression and drives PDAC development by lipid metabolism remodeling. Collectively, this study reveals histone serotonylation as an important driver of PDAC tumorigenesis. The neurotransmitter serotonin regulates cancer through receptor-signaling activation, but also epigenetics mechanisms by serotonylation. Here, the authors show that histone serotonylation promotes pancreatic cancer progression by upregulating stearoyl-CoA desaturase (SCD), which remodels lipid metabolism, suggesting a potential target for therapy.

Scaffold hopping is a key strategy in drug discovery. While one-to-one scaffold hopping strategies are thriving and evolving, one-to-multiple strategies remain challenging to design. We present here a distinct scaffold hopping strategy for the skeletal editing of pyrimidines into a wide range of heteroarenes through the addition of nucleophiles, ring-opening, fragmentation, and ring-closing (ANROFRC) processes. This method features the in situ generation of a vinamidinium salt intermediate, which serves as a unique N-C-C-C four-atom (A4) synthon that reacts with A1 and A2 synthons. Mechanistic studies reveal that C4-aryl substituents play a crucial role in stabilizing the vinamidinium salt intermediate. This work provides a powerful tool for the systematic construction and modification of nitrogen heterocycles, thereby expanding conventional molecular editing techniques. While one-to-one scaffold hopping strategies are thriving and evolving, one-to-multiple strategies remain challenging to design. Here, the authors report a scaffold hopping strategy for the skeletal editing of pyrimidines into a wide range of heteroarenes through the addition of nucleophiles, ring-opening, fragmentation, and ring-closing processes.