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Abstract Background Sorafenib is a standard therapeutic agent for advanced hepatocellular carcinoma (HCC). However, its efficacy is moderate, as the survival of patients is prolonged for only a few months, and the response rate is low. The mechanism of low efficacy remains unclear. In this study, we investigated the effect of Toll-like receptor 3 (TLR3) on the effects of sorafenib on HCC. Methods Polyinosinic-polycytidylic acid [poly(I: C)] was used as a double-stranded RNA analog and TLR3 agonist in subsequent experiments. After orthotopic implantation of HCC tumors in BALBc nu/nu or C57BL/6 mice, survival time, tumor growth, and metastasis in the abdomen and lungs were analyzed. Flow cytometry and cytotoxicity assays were used to analyze NK cells isolated from the spleen or peripheral blood. ELISA was used to detect the expression of plasma interferon (IFN)-γ and monocyte chemoattractant protein (MCP)-1. In addition, the expression of phosphorylated-extracellular regulated kinase 1/2 (pERK1/2), phosphorylated-protein kinase B (pAKT), ERK1/2 and AKT was analyzed by Western blotting. Results Sorafenib reduced the number and activity of NK cells in tumor-bearing mice and simultaneously decreased the levels of MCP-1 and IFN-γ in the plasma. The combination of sorafenib and poly(I: C) synergistically inhibited tumor growth and metastasis in tumor xenograft mice and prolonged survival. Poly(I: C) not only exerts a direct inhibitory effect on tumor growth and metastasis by targeting the TLR3 receptor on tumor cells but also facilitates the proliferation and activation of NK cells, indirectly impeding tumor progression. Mechanistically, poly(I: C) decreased the sorafenib-induced inhibition of ERK phosphorylation and increased the phosphorylation of IκB in NK cells, thereby enhancing NK cell function. Conclusion Activation of TLR3 can enhance the antitumor effect of sorafenib on HCC. The combination of a TLR3 activator and sorafenib may be a new strategy for the treatment of HCC.

To solve the problems of the AC loss in self-field for no-insulation (NI) HTS coils carrying different currents, such as AC transport current, the current scanning inverse in order to decrease the screening current, and so on, by using the T-Ahomogenization model based on the E-J power law, the effects of the transport current, frequency, and the n-value on the magnetic flux density and AC loss of NI-HTS pancack coils were simulated. The instantaneous AC losses of square wave, sawtooth wave, and sinusoidal wave for double-pancake coil were simulated quantitatively. The effects of charging and discharging ramping rates on the current distribution were also discussed by using partial element equivalent circuit (PEEC). The results show that the AC losses increase with the increase of frequency from several hundred to kilo Hz. Due to the transfer of the radial current within coil’s turns, some inverse azimuthal currents may appear in the NI-HTS coil in the early charging period, and some of the azimuthal currents may increase during short discharging period for the same reason. The simulation work can provide some theoretical references for the studies of the stability and AC loss for NI-HTS pancake coils.

Abstract Recently, ZnO‐based composites have been widely applied in the field of electric power. To meet the diverse application requirements, it is necessary to figure out the I–V characteristics of ZnO composites whose high‐voltage and ground‐voltage electrodes are arranged on the opposite sides with a certain horizontal distance. 30 vol%, 40 vol% and 50 vol% ZnO‐based silicone rubber composites were prepared. The horizontal distance between their electrodes was set as 50, 100, 500 μm, 1 and 2 mm, respectively. Results showed that with the increase of ZnO fillers volume fraction under a fixed horizontal distance of 100 μm, from 30 vol% to 50 vol%, the I–V curves shifted left, the leakage current increased and the switching voltage decreased. When the horizontal distance between electrodes increased from 50 μm to 1 mm under a fixed doping concentration of 40%, the I–V curves shifted to the right, the leakage current dropped and the switching voltage rose. The mathematical and physical models were established to explain the results. This work provides a referential significance for the practical application of ZnO composites, such as 5G folding mobile phones and power electronic modules.

Abstract Small-caliber (≤ 6 mm) vascular grafts are commonly used to treat vascular diseases, yet intimal hyperplasia at the distal end-to-side anastomosis remains a significant complication with long-term use. Helical flow has been shown to reduce the risk of cardiovascular complications effectively. Integrating helical flow through an inbuilt helical ridge in vascular grafts is intended to improve hemodynamic performance and mitigate issues such as flow-induced thrombosis and intimal hyperplasia. However, inadequate helical flow strength may limit its effectiveness. This study proposes a novel design for an inbuilt helical ridge in small-caliber grafts to achieve enhanced helical flow. Two novel small-caliber vascular grafts with variable-pitch helical ridges, incorporating both decreasing and increasing pitches, were designed. Their effectiveness was assessed through numerical simulations and in vitro experiments to evaluate their performance in arterial graft applications. The small-caliber vascular grafts incorporating variable-pitch helical ridges significantly improved helical flow structure and distribution, optimized wall shear stress distribution, and reduced platelet adhesion compared to conventional and constant-pitch helical ridge grafts. Among the various new designs, the small-caliber vascular graft featuring decreasing variable-pitch helical ridges has demonstrated better performance. This design is well-suited for small-caliber bypass surgeries, as it is effective in improving hemodynamic performance by improving helical flow into asymmetric structures and increasing helical flow density distribution.

Inert gas argon has important applications in the fields of daily life, industrial manufacture and nuclear environmental monitoring. The key to its application is to selectively and efficiently separate and purify Ar from complex gas components. However, the separation of O2 and Ar at normal temperature is full of challenge due to their similar molecular sizes and adsorption properties as well as their close boiling point. In industry, high purity Ar is mainly produced by low temperature rectification, which is mature technology, but the equipment is large, high-energy consumption and explosive. Adsorption separation is a common method of gas separation. Molecular sieves are the most widely used material due to their huge specific surface area, aboudant pore structure and excellent adsorption properties. The silica tetrahedron in molecular sieve is electrically neutral, while the aluminum tetrahedron is electronegative, which makes it necessary to use H+ or Na+ outside the molecular sieve skeleton to maintain electrical neutrality. In actual application, the interaction between adsorbent and adsorbent can be enhanced by ion-exchange modification of molecular sieve material, so as to effectively improve the O2/Ar separation capacity of molecular sieve. In this paper, the application of ion-exchange modified molecular sieve materials in the field of O2/Ar adsorption separation was systematically summarized and reviewed. The results show that the O2/Ar separation coefficients of molecular sieves modified by alkaline earth metal ions like Ca2+, Sr2+ and Ba2+ can reach about 2.0, while that of Ce3+-exchanged X-type molecular sieve is as high as 5.9, it is an ideal adsorption material for O2/Ar separation. However, the high separation coefficient is limited to the range of low partial pressure, and the O2/Ar separation coefficient under normal pressure is below 2.0. The Ag+-exchanged molecular sieves, namely silver-loaded molecular sieves, have excellent Ar adsorption selectivity. At present, the O2/Ar separation coefficients of silver-loaded molecular sieve materials at atmospheric pressure are around 2.0, but the preparation cost of silver-loaded molecular sieves is high, and it is more suitable for small-scale separation applications, it means that the efficient separation of O2 and Ar at normal temperature and pressure is still challenging. The development of novel ion-exchange modified molecular sieve materials with high adsorption capacity and high adsorption selectivity for the separation of O2 and Ar is still one of the focuses and trends of future research projects.

Abstract Convolutional neural networks (CNNs) for extracting structural information from structural magnetic resonance imaging (sMRI), combined with functional magnetic resonance imaging (fMRI) and neuropsychological features, has emerged as a pivotal tool for early diagnosis of Alzheimer’s disease (AD). However, the fixed-size convolutional kernels in CNNs have limitations in capturing global features, reducing the effectiveness of AD diagnosis. We introduced a group self-calibrated coordinate attention network (GSCANet) designed for the precise diagnosis of AD using multimodal data, including encompassing Haralick texture features, functional connectivity, and neuropsychological scores. GSCANet utilizes a parallel group self-calibrated module to enhance original spatial features, expanding the field of view and embedding spatial data into channel information through a coordinate attention module, which ensures long-term contextual interaction. In a four-classification comparison (AD vs. early MCI (EMCI) vs. late MCI (LMCI) vs. normal control (NC)), GSCANet demonstrated an accuracy of 78.70%. For the three-classification comparison (AD vs. MCI vs. NC), it achieved an accuracy of 83.33%. Moreover, our method exhibited impressive accuracies in the AD vs. NC (92.81%) and EMCI vs. LMCI (84.67%) classifications. GSCANet improves classification performance at different stages of AD by employing group self-calibrated to expand features receptive field and integrating coordinated attention to facilitate significant interactions among channels and spaces. Providing insights into AD mechanisms and showcasing scalability for various disease predictions.

This paper aims to investigate the role of bi-directional shear in the mechanical behaviour of granular materials and macro-micro relations by conducting experiments and discrete element method (DEM) modelling. The bi-directional shear consists of a static shear consolidation and subsequent shear under constant vertical stress and constant volume conditions. A side wall node loading method is used to exert bi-directional shear of various angles. The results show that bi-directional shear can significantly influence the mechanical behaviour of granular materials. However, the relationship between bi-directional shear and mechanical responses relies on loading conditions, i.e. constant vertical stress or constant volume conditions. The stress states induced by static shear consolidation are affected by loading angles, which are enlarged by subsequent shear, consistent with the relationship between bi-directional shear and principal stresses. It provides evidence for the dissipation of stresses accompanying static liquefaction of granular materials. The presence of bi-directional principal stress rotation (PSR) is demonstrated, which evidences why the bi-directional shear of loading angles with components in two directions results in faster dissipations of stresses with static liquefaction. Contant volume shearing leads to cross-anisotropic stress and fabric at micro-contacts, but constant vertical stress shearing leads to complete anisotropic stress and fabric at micro-contacts. It explains the differentiating relationship between stress-strain responses and fabric anisotropy under these two conditions. Micromechanical signatures such as the slip state of micro-contacts and coordination number are also examined, providing further insights into understanding granular behaviour under bi-directional shear.

Abstract This study compares the surface patina of ancient tin rich bronze with pure hydrothermally synthesized SnO2 nanoparticles using various analytical techniques, including metallographic microscopy, scanning electron microscopy, transmission electron microscopy, energy dispersive spectroscopy, X-ray diffraction, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and high-angle annular dark-field scanning transmission electron microscopy. The primary crystalline component of the patina consists of approximately 5 nm SnO2 nanoparticles, which closely resemble pure SnO2, indicating their comparability. Cu was also detected in the patina; however, it did not form crystalline structures. The X-ray diffraction results showed a shift in the patina’s peak, suggesting the infiltration of Cu into the SnO2 lattice, which compromises its crystallinity. In comparison to synthetic SnO2, the X-ray photoelectron spectroscopy spectra of the patina revealed novel peaks corresponding to both Cu and O, indicating the presence of Cu−O−Sn bonding—a characteristic feature of type-I patina. This suggests that the primary structure of type-I patina consists of crystalline SnO2 nanoparticles, with a limited amount of Cu integrated into its lattice configuration. The concentration of Cu within the SnO2 crystal units is restricted, leading primarily to the formation of amorphous Cu2O in conjunction with Sn. The presence of Sn enhances the structural stability of Cu2O, facilitating its incorporation while inhibiting the crystallization of Cu2O. However, when the Sn concentration is insufficient, an inadequate Cu–O−Sn amorphous phase may form, allowing for the potential crystallization of Cu2O.

Abstract Background Bilateral malignant glaucoma induced by a capsular tension ring associated with ring-shaped cysts of the ciliary body post-cataract surgery is rare. Herein, we present a case to highlight the possibility of capsular tension ring-induced malignant glaucoma. Case presentation A 59-year-old woman underwent phacoemulsification combined with capsular tension ring implantation for cataracts and zonular fibre laxity in both eyes. Upon admission, annular ciliary masses were detected in both eyes using ultrasound biomicroscopy. Two months post-surgery, the patient experienced vision deterioration, high intraocular pressure, and an axial shallowing anterior chamber in the right eye, and responded poorly to traditional anti-glaucoma medication. Ten days later, similar symptoms appeared in the left eye. Ultrasound biomicroscopy detected contact between the ciliary body and the capsular tension ring. Subsequently, malignant glaucoma was diagnosed. Anterior and posterior capsulotomies performed peripheral to intraocular lens optics using neodymium: YAG laser restored communication and alleviated the symptoms. A one-year follow-up revealed stable intraocular pressure and anterior chamber in both eyes. Conclusions This is the first case report of bilateral malignant glaucoma after cataract surgery induced by capsular tension ring, which is associated with bilateral ring-shaped cysts of the ciliary body. Blockage between the ciliary body and capsular tension ring was confirmed using ultrasound biomicroscopy.

Abstract Background The mutations of oncogenic epidermal growth factor receptor (EGFR) is an important cause of lung adenocarcinoma (LUAD) malignance. It has been knowm that metabolic reprogramming is an important hallmark of malignant tumors, and purine metabolism is a key metabolic pathway for tumor progression and drug resistance, but its relationship with the EGFR-mutant LUAD is unclear. Methods Metabolic reprogramming was studied through capillary electrophoresis-time of flight mass spectrometry (CE-TOF/MS)-based metabolic profiling analysis. Cell proliferation in vitro was evaluated by EdU staining and cell cycle assay. Tumorigenicity in vivo was tested by subcutaneous tumor formation experiment in nude mice. The binding of hypoxia-inducible factor-1 alpha (HIF-1α) and hypoxanthine phosphoribosyltransferase 1 (HPRT1) was detected by DNA pull‑down assay and Chromatin immunoprecipitation (ChIP) assays. HIF-1α, HPRT1, DNA damage and cell apoptosis related genes were examined by western blot. In addition, RNA sequencing, mass spectrometry and bioinformatics analysis were performed. Results We found that mutated EGFR (muEGFR) upregulates HPRT1 to promote purine metabolism and tumorigenesis of EGFR-mutant LUAD. Mechanistically, muEGFR increases HIF-1α expression through protein stability. Meanwhile, up-regulated HIF-1α bound to the promoter of HPRT1 and transcriptionally activates HPRT1 expression, enhancing purine metabolism to maintain rapid tumor cell proliferation in EGFR-mutant LUAD. Further, gefitinib inhibited the synthesis of purine nucleotides, and HPRT1 inhibition increased the sensitivity of gefitinib to EGFR-mutant LUAD. Conclusions Our study reveals that muEGFR-HIF-1α-HPRT1 axis plays a key role in EGFR-mutant LUAD and provides a new strategy-inhibiting purine metabolism for treating EGFR-mutant LUAD.

Penicillium citrinum is one of the most prevalent tobacco spoilage fungi. However, the mechanisms underlying fungal growth on tobacco leaves remain largely unknown. In this study, transcriptomic analyses were performed to reveal the genome-wide expression profiles of P. citrinum growing on tobacco leaves. First, a comparative analysis was conducted between two sets of transcriptomic data from P. citrinum growing on chemically defined media and tobacco leaves. Enrichment analyses showed that differentially regulated genes were mainly associated with carbohydrate degradation (e.g., cellulose, pectin, and xylan) and the catabolism of fatty acids and aromatic compounds. Comparative transcriptomic analyses between different time points indicated that the fungal transcriptome varied dynamically during the spoilage process, and the enriched terms were associated with small-molecule degradation and fungal development. Enrichment analyses indicated that more up-regulated genes appeared in all enriched Gene Ontology terms. Notably, more organelles significantly contributed to further fungal growth on tobacco leaves. In conclusion, P. citrinum activates a comprehensive transcriptome that changes dynamically when causing tobacco mildew.

Abstract Background Gastroschisis is a common abdominal wall defect that increases infant mortality risk and health care costs. However, recent epidemiological data on gastroschisis in China is limited. Methods Using 2007–2020 data from the Chinese Birth Defects Monitoring Network (CBDMN), we analyzed gastroschisis prevalence rates stratified by birth year, maternal age group, residence area, geographical region, and infant sex. We also examined the temporal variations in prevalence, pregnancy outcomes of affected infants, prenatal diagnoses, and co-occurring anomalies. Results From 2007 to 2020, a total of 6,813 cases of gastroschisis were identified among 25,909,000 births, comprising 4,675 isolated and 2,138 non-isolated cases. Prevalence rates per 10,000 live and still births were 2.63, 1.80, and 0.83 for the overall, isolated, and non-isolated gastroschisis, respectively, all showing a decreasing trend over the study period. The prevalence of overall gastroschisis varied significantly by maternal age (

Abstract Background Lung squamous cell carcinoma (LUSCs) is associated with high mortality (20–30%) and lacks of effective treatments. Almost all LUSC exhibit somatic mutations in TP53. Wee1, a tyrosine kinase, regulates the cell cycle at the G2/M checkpoint. In TP53-deficient cells, the dependence on G2/M checkpoints increases. PD0166285 is the first reported drug with inhibitory activity against both Wee1 and PKMYT1. Methods Protein expression was determined by Western blot analysis. Cell proliferation was assessed using cell colony formation and CCK-8 assays. Cell cycle was performed by PI staining with flow cytometry. Apoptosis was evaluated using Annexin V-Phycoerythrin double staining and flow cytometry. DNA damage was detected through comet assay and immunofluorescence assay. In vivo, apoptosis and anti-tumor effects were assessed using the TUNEL assay, a nude mouse model, and immunohistochemistry (IHC). Co-immunoprecipitation assay was used to detect protein–protein interactions. We analyzed Wee1, PKMYT1, and Stat1 expression in pan-cancer studies using the Ualcan public database and assessed their prognostic implications with Kaplan–Meier curves. Result PD0166285, a Wee1 inhibitor, effectively inhibits Wee1 activity, promoting cell entry into a mitotic crisis. Moreover, PD0166285 sensitizes cells to cisplatin, enhancing clinical outcomes. Our study demonstrated that PD016628 regulates the cell cycle through Rad51 and results in cell cycle arrest at the G2/M phase. We observed increased apoptosis in tumor cells treated with PD0166285, particularly when combined with cisplatin, indicating an enhanced apoptotic response. The upregulation of γ-H2AX serves as an indicator of mitotic catastrophe. Co-immunoprecipitation and data analysis revealed that apoptosis in LUSC is mediated through the Stat1 pathway, accompanied by decreased levels of Socs3. Furthermore, IHC staining confirmed significant differences in the expression of Phospho-CDK1 and γ-H2AX in LUSCs, suggesting involvement in DNA damage. Conclusions In summary, our study suggests that PD0166285, an inhibitor of Wee1, sensitizes LUSC cells to cisplatin and modulates DNA damage and apoptosis pathways through Rad51 and Stat1, respectively. These findings highlight the combination of PD0166285 and cisplatin as a promising therapeutic approach for treating LUSC.

Abstract Malignant transformation (MT) is commonly seen in IDH-mutant gliomas. There has been a growing research interest in revealing its underlying mechanisms and intervening prior to MT at the early stages of the transforming process. Here we established a unique pair of matched 3D cell models: 403L, derived from a low-grade glioma (LGG), and 403H, derived from a high-grade glioma (HGG), by utilizing IDH-mutant astrocytoma samples from the same patient when the tumor was diagnosed as WHO grade 2 (tumor mutational burden (TMB) of 3.96/Mb) and later as grade 4 (TMB of 70.07/Mb), respectively. Both cell models were authenticated to a patient’s sample retaining endogenous expression of IDH1 R132H. DNA methylation profiles of the parental tumors referred to LGG and HGG IDH-mutant glioma clusters. The immunopositivity of SOX2, NESTIN, GFAP, OLIG2, and beta 3-Tubulin suggested the multilineage potential of both models. 403H was more prompt to cell invasion and developed infiltrative HGG in vivo. The differentially expressed genes (DEGs) from the RNA sequencing analysis revealed the tumor invasion and aggressiveness related genes exclusively upregulated in the 403H model. Pathway analysis showcased an enrichment of genes associated with epithelial-mesenchymal transition (EMT) and Notch signaling pathways in 403H and 403L, respectively. Mass spectrometry-based targeted metabolomics and hyperpolarized (HP) 1-13C pyruvate in-cell NMR analyses demonstrated significant alterations in the TCA cycle and fatty acid metabolism. Citrate, glutamine, and 2-HG levels were significantly higher in 403H. To our knowledge, this is the first report describing the development of a matched pair of 3D patient-derived cell models representative of MT and temozolomide (TMZ)-induced hypermutator phenotype (HMP) in IDH-mutant glioma, providing insights into genetic and metabolic changes during MT/HMP. This novel in vitro model allows further investigation of the mechanisms of MT at the cellular level. Graphic Abstract

Rattus tanezumi (Niethammer, 1975) is one of the commensal rodent species in South China. With the development of transportation and climate change, R. tanezumi has gradually migrated north and become the dominant rat species for the past few years. In this study, we assembled a complete mitochondrial genome of R. tanezumi, captured from North China. The mitogenome contains 16,307 nucleotide pairs, including 13 protein-coding genes, 2 ribosomal RNA genes, and 22 transfer RNA genes, as well as one non-coding control region. Based on whole mitogenome phylogenetical analysis showed that R. tanezumi captured from North China had a close phylogenetic relationship with that from Japan and South Korea. These findings are valuable for further studies on the evolution, genetic diversity, and taxonomy of Asian commensal rodent.

Abstract Alterations in the reward and cognitive control systems are commonly observed among adolescents with internet dependence (ID), and this impairment is often accompanied by social dysfunctions, such as academic burnout. However, the intercorrelations among ID, reward, cognitive control processing, and learning burnout remain unclear. We recruited 1074 Chinese adolescents to investigate the complex interrelationships among these variables using network analysis. The resulting network revealed patterns that connected ID to the behavioral inhibition/activation system (BIS/BAS), self-control, and learning burnout; these results exhibited reasonable stability and test–retest consistency. Throughout the network, the node of BAS-drive was the critical influencing factor, and the node of self-control was the protection factor. In addition, several symptoms of learning burnout and ID were positively associated with sensitivity to punishment. As revealed by the network comparison test, the network constructed among internet dependent (ID) group differed from the network constructed among internet nondependent (IND) group not only in the edges between BIS and learning burnout but also in terms of the edges associated with learning burnout. In conclusion, this study provides insights into the complex mechanisms underlying ID among adolescents from the perspective of the network relationships between core influencing factors and negative consequences. It validates the dual-system model of risky behavior among adolescents and offers a foundation for early warning and interventions for ID in this context.

Background: In the recent decade, there has been substantial progress in the technologies and philosophies associated with diagnosing and treating anterior cruciate ligament (ACL) injuries in China. The therapeutic efficacy of ACL reconstruction in re-establishing the stability of the knee joint has garnered widespread acknowledgment. However, the path toward standardizing diagnostic and treatment protocols remains to be further developed and refined. Objective: In this context, the Chinese Association of Orthopaedic Surgeons (CAOS) and the Chinese Society of Sports Medicine (CSSM) collaboratively developed an expert consensus on diagnosing and treating ACL injury, aiming to enhance medical quality through refining professional standards. Methods: The consensus drafting team invited experts across the Greater China region, including the mainland, Hong Kong, Macau, and Taiwan, to formulate and review the consensus using a modified Delphi method as a standardization approach. As members of the CSSM Lower Limb Study Group and the CAOS Arthroscopy and Sports Medicine Study Group, invited experts concentrated on two pivotal issues: “Graft Selection” and “Clinical Outcome Evaluation” during the second part of the consensus development. Results: This focused discussion ultimately led to a strong consensus on nine specific consensus terms. Conclusion: The consensus clearly states that ACL reconstruction has no definitive “gold standard” graft choice. Autografts have advantages in healing capability but are limited in availability and have potential donor site morbidities; allografts reduce surgical trauma but incur additional costs, and there are concerns about slow healing, quality control issues, and a higher failure rate in young athletes; synthetic ligaments allow for early rehabilitation and fast return to sport, but the surgery is technically demanding and incurs additional costs. When choosing a graft, one should comprehensively consider the graft's characteristics, the doctor's technical ability, and the patient's needs. When evaluating clinical outcomes, it is essential to ensure an adequate sample size and follow-up rate, and the research should include patient subjective scoring, joint function and stability, complications, surgical failure, and the return to sport results. Medium and long-term follow-ups should not overlook the assessment of knee osteoarthritis.

Cathepsin L (CTSL) is a promising therapeutic target for metabolic disorders. Current pharmacological interventions targeting CTSL have demonstrated potential in reducing body weight gain, serum insulin levels, and improving glucose tolerance. However, the clinical application of CTSL inhibitors remains limited. In this study, we used a combination of artificial intelligence and experimental methods to identify new CTSL inhibitors from natural products. Through a robust deep learning model and molecular docking, we screened 150 molecules from natural products for experimental validation. At a concentration of 100 µM, we found that 36 of them exhibited more than 50 % inhibition of CTSL. Notably, 13 molecules displayed over 90 % inhibition and exhibiting concentration-dependent effects. The molecular dynamics simulation on the two most potent inhibitors, Plumbagin and Beta-Lapachone, demonstrated stable interaction at the CTSL active site. Enzyme kinetics studies have shown that these inhibitors exert an uncompetitive inhibitory effect on CTSL. In conclusion, our research identifies Plumbagin and Beta-Lapachone as potential CTSL inhibitors, offering promising candidates for the treatment of metabolic disorders and illustrating the effectiveness of artificial intelligence in drug discovery.

In this paper, the following critical Kirchhoff-type elliptic equation involving a logarithmic-type perturbation$ -\Big(a+b\int_{\Omega}|\nabla u|^2\mathrm{d}x\Big)\Delta u = \lambda|u|^{q-2}u\ln |u|^2+\mu|u|^2u $is considered in a bounded domain in $ \mathbb{R}^{4} $. One of the main obstructions one encounters when looking for weak solutions to Kirchhoff problems in high dimensions is that the boundedness of the $ (PS) $ sequence is hard to obtain. By combining a result by Jeanjean [27] with the mountain pass lemma and Brézis–Lieb's lemma, it is proved that either the norm of the sequence of approximation solutions goes to infinity or the problem admits a nontrivial weak solution, under some appropriate assumptions on $ a $, $ b $, $ \lambda $, and $ \mu $.

Abstract Background Hagfishes are fascinating creatures that typically inhabit the deep sea. The deep sea is characterized by its lack of sunlight, primary productivity, and diminishing biomass with increasing ocean depth. Therefore, hagfishes living in this environment must develop effective survival strategies to adapt to the limited food supply. Deep-sea hagfishes have been observed to survive without food intake for up to one year. In this study, we have assembled a high-quality somatic genome of the deep-sea hagfish (Eptatretus okinoseanus) captured below 1,000 m. We compared the genome of E. okinoseanus with the genomes of inshore hagfish, lampreys, and other related species to investigate the genetic factors underlying the deep-sea hagfish adaptations to the environment. Results The E. okinoseanus somatic genome was estimated to be 1.89 Gb and assembled into 17 pseudochromosomes. Phylogenetic analysis showed that shallow-sea and deep-sea hagfishes diverged approximately 58.8 million years ago. We found Perilipin gene family was significantly expanded in deep sea E. okinoseanus, which promotes triacylglycerol storage. Furthermore, a series of genes involved in fatty acid synthesis and metabolism, blood glucose regulation, and metabolic rate regulation were also expanded, rapid evolution or positive selection, and these changes contribute to their efficiency in energy utilization. Among these genes, the positively selected gene JNK may play an important role in energy metabolism. In addition, the olfactory receptors of the deep-sea hagfish were significantly expanded to 86, and three conserved motifs present only in hagfishes olfactory receptors were identified, which may facilitate the rapid localization of carrion. Conclusions This study provides valuable genomic resources for insights into the survival strategies of deep-sea hagfishes in oligotrophic environments.

Abstract The freezing and thawing cycle is one of the primary causes of damage and instability to buildings in seasonal frost regions. During this process, the mechanical properties of soil are affected, leading to settlement, cracking, or deformation of infrastructure. Mitigating or reducing the occurrence of building frost damage in seasonal frost regions has become an important subject of study. Freeze–thaw (F–T) action will influence the distribution of moisture inside the reinforced soil and change the strength of thawing soil, which is closely related to the main influencing factors, such as initial moisture content, compaction degree, reinforced spacing, number of freeze–thaw cycles (FTC), freezing temperature, and effective vertical stress. Cohesion is an important index to determine the shear strength of clay, which is important to analyze the change in cohesion after F–T. Meanwhile, cohesion is closely related to soil moisture content. This study conducted orthogonal experiments on these primary influencing factors (6 factors at 5 levels) through FTC tests, triaxial tests, and moisture content tests to determine the undrained cohesion and moisture content of the clay after FTC, thereby establishing the influence of reinforcement on soil strength under freeze–thaw conditions. Based on the experimental results, SPSS software was used to fit the regression equations of undrained cohesion and moisture content expressed by the main influencing factors at different heights of the clay. Optimization options for the main influencing factors were obtained with Matlab software when the highest undrained cohesion values 6.8, 10.6, 8.9 kPa and lowest moisture content values 24.0%, 24.3%, 26.2% appeared in upper, middle and lower parts of the testing clay structure respectively, in conditions of − 15 °C freezing temperature and 5 times FTC. And determined the optimal combinations of moisture content, reinforcement spacing, compaction density, and vertical load at different heights. Decreasing reinforced spacing in silty clay was beneficial for liquid underwater seepage after F–T. The redistribution of internal moisture in the soil sample strengthened its undrained cohesion, thereby increasing the soil's shear strength. Comparing reinforcement conditions at different locations, it was found that when there were 3 layers of reinforcement with a spacing of 150 mm between them, this spacing was optimal. It played a significant role in improving the soil's shear strength and enhancing its bearing capacity. For reinforced clay itself, the order of the main factors influencing the undrained cohesion of soil after F–T, from high to low, was initial moisture content, reinforced spacing, and compaction degree.

Abstract It has been shown that noise emissions from HV overhead line conductors can be reduced under rain conditions by making their surfaces superhydrophobic. The working environment makes ensuring the longevity of any treatment a major challenge. The degradation of various superhydrophobic surfaces generated by applying a superhydrophobic coating and patterning microscale channels is assessed under an AC electric field (18 kV/cm) with continuous water spray. By examining the droplet distribution on the surfaces during the degradation and the surface roughness before and after degradation, the authors demonstrate that no water droplets were found on the microscale patterned surface, but droplets were formed on the coated surface after degradation. The surface roughness reduction of the coated surface and microscale patterned surface was 29.8% and 11.3%, respectively, indicating that the microscale patterned surface has better durability than the superhydrophobic coating under the AC electric stress.

Abstract Biological networks serve a crucial role in elucidating intricate biological processes. While interspecies environmental interactions have been extensively studied, the exploration of gene interactions within species, particularly among individual microorganisms, is less developed. The increasing amount of microbiome genomic data necessitates a more nuanced analysis of microbial genome structures and functions. In this context, we introduce a complex structure using higher-order network theory, “Solid Motif Structures (SMS)”, via a hierarchical biological network analysis of genomes within the same genus, effectively linking microbial genome structure with its function. Leveraging 162 high-quality genomes of Microcystis, a key freshwater cyanobacterium within microbial ecosystems, we established a genome structure network. Employing deep learning techniques, such as adaptive graph encoder, we uncovered 27 critical functional subnetworks and their associated SMSs. Incorporating metagenomic data from seven geographically distinct lakes, we conducted an investigation into Microcystis’ functional stability under varying environmental conditions, unveiling unique functional interaction models for each lake. Our work compiles these insights into an extensive resource repository, providing novel perspectives on the functional dynamics within Microcystis. This research offers a hierarchical network analysis framework for understanding interactions between microbial genome structures and functions within the same genus.

Abstract Vitamin D deficiency is increasingly common in systemic lupus erythematosus (SLE) patients and is associated with the disease activity and proteinuria. Recently, alterations in metabolism have been recognized as key regulators of SLE pathogenesis. Our objective was to identify differential metabolites in the serum metabolome of SLE with vitamin D deficiency. In this study, serum samples from 31 SLE patients were collected. Levels of 25(OH)D3 were assayed by ELISA. Patients were divided into two groups according to their vitamin D level (20 ng/ml). Untargeted metabolomics were used to study the metabolite profiles in serum by high-performance liquid chromatography-tandem mass spectrometry. Subsequently, we performed metabolomics profiling analysis to identify 52 significantly altered metabolites in vitamin D deficient SLE patients. The area under the curve (AUC) from ROC analyses was calculated to assess the diagnostic potential of each candidate metabolite biomarker. Lipids accounted for 66.67% of the differential metabolites in the serum, highlighted the disruption of lipid metabolism. The 52 differential metabolites were mapped to 27 metabolic pathways, with fat digestion and absorption, as well as lipid metabolism, emerging as the most significant pathways. The AUC of (S)-Oleuropeic acid and 2-Hydroxylinolenic acid during ROC analysis were 0.867 and 0.833, respectively, indicating their promising diagnostic potential. In conclusion, our results revealed vitamin D deficiency alters SLE metabolome, impacting lipid metabolism, and thrown insights into the pathogenesis and diagnosis of SLE.

Abstract Derived from enteroendocrine cells (EECs), glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are pivotal incretin hormones crucial for blood glucose regulation. Medications of GLP-1 analogs and GLP-1 receptor activators are extensively used in the treatment of type 2 diabetes (T2D) and obesity. However, there are currently no agents to stimulate endogenous incretin secretion. Here, we find the pivotal role of KCNH2 potassium channels in the regulation of incretin secretion. Co-localization of KCNH2 with incretin-secreting EECs in the intestinal epithelium of rodents highlights its significance. Gut epithelial cell-specific KCNH2 knockout in mice improves glucose tolerance and increases oral glucose-triggered GLP-1 and GIP secretion, particularly GIP. Furthermore, KCNH2-deficient primary intestinal epithelial cells exhibit heightened incretin, especially GIP secretion upon nutrient stimulation. Mechanistically, KCNH2 knockdown in EECs leads to reduced K+ currents, prolonged action potential duration, and elevated intracellular calcium levels. Finally, we found that dofetilide, a KCNH2-specific inhibitor, could promote incretin secretion in enteroendocrine STC-1 cells in vitro and in hyperglycemic mice in vivo. These findings elucidate, for the first time, the mechanism and application of KCNH2 in regulating incretin secretion by EECs. Given the therapeutic promise of GLP-1 and GIP in diabetes and obesity management, this study advances our understanding of incretin regulation, paving the way for potential incretin secretagogue therapies in the treatment of diabetes and obesity.

Abstract Background Influenza, an acute infectious respiratory disease, presents a significant global health challenge. Accurate prediction of influenza activity is crucial for reducing its impact. Therefore, this study seeks to develop a hybrid Convolution Neural Network—Long Short Term Memory neural network (CNN-LSTM) model to forecast the percentage of influenza-like-illness (ILI) rate in Hebei Province, China. The aim is to provide more precise guidance for influenza prevention and control measures. Methods Using ILI% data from 28 national sentinel hospitals in the Hebei Province, spanning from 2010 to 2022, we employed the Python deep learning framework PyTorch to develop the CNN-LSTM model. Additionally, we utilized R and Python to develop four other models commonly used for predicting infectious diseases. After constructing the models, we employed these models to make retrospective predictions, and compared each model’s prediction performance using mean absolute error (MAE), root mean square error (RMSE), mean absolute percentage error (MAPE), and other evaluation metrics. Results Based on historical ILI% data from 28 national sentinel hospitals in Hebei Province, the Seasonal Auto-Regressive Indagate Moving Average (SARIMA), Extreme Gradient Boosting (XGBoost), Convolution Neural Network (CNN), Long Short Term Memory neural network (LSTM) models were constructed. On the testing set, all models effectively predicted the ILI% trends. Subsequently, these models were used to forecast over different time spans. Across various forecasting periods, the CNN-LSTM model demonstrated the best predictive performance, followed by the XGBoost model, LSTM model, CNN model, and SARIMA model, which exhibited the least favorable performance. Conclusion The hybrid CNN-LSTM model had better prediction performances than the SARIMA model, CNN model, LSTM model, and XGBoost model. This hybrid model could provide more accurate influenza activity projections in the Hebei Province.

Abstract Thermal management emerges as a grand challenge of next-generation electronics. Efforts to develop compact, solid-state cooling devices have led to the exploration of the electrocaloric effect of ferroelectric polymers. Despite recent advances, the applications of electrocaloric polymers on electronics operating at elevated temperatures remain essentially unexplored. Here, we report that the ferroelectric polymer composite composed of highly-polarized barium strontium titanate nanofibers and electron-accepting [6,6] phenyl-C61-butyric acid methyl ester retains fast electrocaloric responses and stable cyclability at elevated temperatures. We demonstrate the effectiveness of electrocaloric cooling in a polymer composite for a pyroelectric energy harvesting device. The device utilizes a simulated central processing unit (CPU) as the heat source. Our results show that the device remains operational even when the CPU is overheated. Furthermore, we show that the composite functions simultaneously as a pyroelectric energy converter to harvest thermal energy from an overheated chip into electricity in the electrocaloric process. This work suggests a distinct approach for overheating protection and recycling waste heat of microelectronics.

Abstract Inferior vena cava filter (IVCF) implantation is a common method of thrombus capture. By implanting a filter in the inferior vena cava (IVC), microemboli can be effectively blocked from entering the pulmonary circulation, thereby avoiding acute pulmonary embolism (PE). Inspired by the helical flow effect in the human arterial system, we propose a helical retrievable IVCF, which, due to the presence of a helical structure inducing a helical flow pattern of blood in the region near the IVCF, can effectively avoid the deposition of microemboli in the vicinity of the IVCF while promoting the cleavage of the captured thrombus clot. It also reduces the risk of IVCF dislodging and slipping in the vessel because its shape expands in the radial direction, allowing its distal end to fit closely to the IVC wall, and because its contact structure with the inner IVC wall is curved, increasing the contact area and reducing the risk of the vessel wall being punctured by the IVCF support structure. We used ANSYS 2023 software to conduct unidirectional fluid–structure coupling simulation of four different forms of IVCF, combined with microthrombus capture experiments in vitro, to explore the impact of these four forms of IVCF on blood flow patterns and to evaluate the risk of IVCF perforation and IVCF dislocation. It can be seen from the numerical simulation results that the helical structure does have the function of inducing blood flow to undergo helical flow dynamics, and the increase in wall shear stress (WSS) brought about by this function can improve the situation of thrombosis accumulation to a certain extent. Meanwhile, the placement of IVCF will change the flow state of blood flow and lead to the deformation of blood vessels. In in vitro experiments, we found that the density of the helical support rod is a key factor affecting the thrombus trapping efficiency, and in addition, the contact area between the IVCF and the vessel wall has a major influence on the risk of IVCF displacement.

Abstract Room-temperature elastocaloric cooling is considered as a zero-global-warming-potential alternative to conventional vapor-compression refrigeration technology. However, the limited entropy and large-deformation features of elastocaloric polymers hinder the creation of the breakthrough in their caloric responses and device development. Herein, we report that the addition of a small amount of inorganic nanofillers into the polymer induces the aggregate of the effective elastic chains via shearing the interlaminar molecular chains, which provides an additional contribution to the entropy in elastocaloric polymers. Consequently, the adiabatic temperature change of −18.0 K and the isothermal entropy change of 187.4 J kg−1 K−1 achieved in the polymer nanocomposites outperform those of current elastocaloric polymers. Moreover, a large-deformation cooling system with a work recovery efficiency of 56.3% is demonstrated. This work opens a new avenue for the development of high-performance elastocaloric polymers and prototypes for solid-state cooling applications.

Sliding bearings are crucial rotating mechanical components in nuclear power plants, and their failures can result in severe economic losses and human casualties. Deep learning provides a new approach to bearing fault diagnosis, but there is currently a lack of a universal fault diagnosis model for studying bearing-rotor systems under various operating conditions, speeds and faults. Research on bearing-rotor systems supported by sliding bearings is limited, leading to insufficient fault data. To address these issues, this paper proposes a fault diagnosis model framework for bearing-rotor systems based on a deep convolutional generative adversarial network (TF-DLGAN). This model not only exhibits outstanding fault diagnosis performance but also addresses the issue of insufficient fault data. An experimental platform is constructed to conduct fault experiments under various operating conditions, speeds and faults, establishing a dataset for sliding bearing-rotor system faults. Finally, the model's effectiveness is validated using this dataset.

Self-directed learning with mobile technology (SDLMT) is critical to students’ learning success. However, only minimal research has been conducted on the manner by which significant aspects (e.g., self-efficacy, student engagement) are related to SDLMT. This study analyzed the answers of 485 Chinese students (seventh to ninth grades) who were surveyed, and evaluated the relationships among self-efficacy (Internet self-efficacy and online communication self-efficacy), student engagement (behavioral, cognitive, emotional, and social engagement), and SDLMT. Structural equation model revealed that SDLMT was positively predicted by self-efficacy, and SDLMT was positively impacted by student engagement. Moreover, the mediation analysis was performed using the PROCESS plugin in SPSS and determined that after controlling for gender and grade, the relationship between self-efficacy and SDLMT was partially mediated by student engagement. Findings established the value of self-efficacy for SDLMT, and further emphasized the vital mediating role of student engagement. Hence, developing K–12 students’ SDLMT entails enhancing self-efficacy and student engagement.

Abstract Background Kinesiophobia after percutaneous coronary intervention (PCI) may lead to decreased compliance with rehabilitation exercises. Effective interventions are essential to overcome kinesiophobia after PCI. The aim of this trial is to investigate the clinical effects of an intervention based on the fear-avoidance model (FAM) on kinesiophobia in post-PCI patients. Methods Eighty participants will be recruited in the Department of Cardiology in Hebei Provincial People’s Hospital. And they will be randomly allocated to the test group and undergo a 5-day step-to-step intervention. The primary outcome will be the scores of a scale on kinesiophobia. Secondary outcome measures included self-efficacy for exercise, psychogenic anxiety, and the occurrence of cardiovascular adverse events. Primary and secondary outcome data will be collected at baseline (t 0), on the day of discharge (t 1), and one month after discharge (t 2). Discussion The effectiveness of an intervention based on the FAM to increase exercise self-efficacy and decrease kinesiophobia in post-PCI patients will be demonstrated. The findings of this study will facilitate post-PCI patients to participate in cardiac rehabilitation. Trial registration ChiCTR2200065649 Effect of an intervention based on the fear-avoidance model on exercise fear in patients after percutaneous coronary intervention. Registered on November 10, 2022.

Cross-species research has advanced human understanding of brain regions, with cross-species comparisons using magnetic resonance imaging technology becoming increasingly common. Currently, cross-species research on human language regions has primarily focused on traditional brain areas such as the Broca region. While some studies have indicated that human language function also involves other language regions, the corresponding relationships between these brain regions in humans and macaques remain unclear. This study calculated the strength of the connections between the high-level language processing regions in human and macaque brains, identified homologous target areas based on the structural connections of white-matter fiber bundles, and compared the connectivity profiles of both species. The results of the experiment demonstrated that macaques possess brain regions which exhibit connectivity patterns resembling those found in human high-level language processing regions. This discovery suggests that while the function of a human brain region is specialized, it still maintains a structural connectivity similar to that seen in macaques.

Abstract Studies have demonstrated that prior to puberty, girls have a lower incidence and severity of asthma symptoms compared to boys. This study aimed to explore the role of progesterone (P4), a sex hormone, in reducing inflammation and altering the immune microenvironment in a mouse model of allergic asthma induced by OVA. Female BALB/c mice with or without ovariectomy to remove the influence of sex hormones were used for the investigations. Serum, bronchoalveolar lavage fluid (BALF), and lung tissue samples were collected for analysis. The results indicated that P4 treatment was effective in decreasing inflammation and mucus secretion in the lungs of OVA-induced allergic asthma mice. P4 treatment also reduced the influx of inflammatory cells into the BALF and increased the levels of Th1 and Th17 cytokines while decreasing the levels of Th2 and Treg cytokines in both BALF and lung microenvironment CD45+ T cells. Furthermore, P4 inhibited the infiltration of inflammatory cells into the lungs, suppressed NETosis, and reduced the number of pulmonary CD4+ T cells while increasing the number of regulatory T cells. The neutrophil elastase inhibitor GW311616A also suppressed airway inflammation and mucus production and modified the secretion of immune Th1, Th2, Th17, and Treg cytokines in lung CD45+ immune cells. These changes led to an alteration of the immunological milieu with increased Th1 and Th17 cells, accompanied by decreased Th2, Treg, and CD44+ T cells, similar to the effects of P4 treatment. Treatment with P4 inhibited NETosis by suppressing the p38 pathway activation, leading to reduced reactive oxygen species production. Moreover, P4 treatment hindered the release of double-stranded DNA during NETosis, thereby influencing the immune microenvironment in the lungs. These findings suggest that P4 treatment may be beneficial in reducing inflammation associated with allergic asthma by modulating the immune microenvironment. In conclusion, this research indicates the potential of P4 as a therapeutic agent for ameliorating inflammation in OVA-induced allergic asthma mice.

Objective To explore the mechanism of bifendate derivatives in improving diabetic nephropathy and renal function. Methods Fifty SPF grade 6-8 week old C57BL/6J mice, of which, 15 were in the control group and 35 in the diabetic nephropathy model group. The mice in the control group were divided into a normal control group (n=7) and a control administration group (n=8), and the mice in the diabetic nephropathy model group were divided into model group, low-dose administration group, medium-dose administration group, high-dose administration group, and resveratrol-positive drug group (each had 7 mice). Samples were taken after 8 weeks of drug administration. The basic parameters and renal function related indexes of mice were detected, glycogen staining experiments detected the accumulation of glycogen in renal tissues, Sirius red staining detected the fibrosis of renal tissues, and proteomic analysis was performed by Q-Exactive mass spectrometer. The differences of the indexes between the comparison groups were analyzed. Results Different doses of bifendate derivatives significantly reduced fasting blood glucose in mice (P

Abstract Molecular structure-editing through nitrogen insertion offers more efficient and ingenious pathways for the synthesis of nitrogen-containing compounds, which could benefit the development of synthetic chemistry, pharmaceutical research, and materials science. Substituted amines, especially nitrogen-containing alkyl heterocyclic compounds, are widely found in nature products and drugs. Generally, accessing these compounds requires multiple steps, which could result in low efficiency. In this work, a molecular editing strategy is used to realize the synthesis of nitrogen-containing compounds using aryl alkanes as starting materials. Using derivatives of O-tosylhydroxylamine as the nitrogen source, this method enables precise nitrogen insertion into the Csp 2-Csp 3 bond of aryl alkanes. Notably, further synthetic applications demonstrate that this method could be used to prepare bioactive molecules with good efficiency and modify the molecular skeleton of drugs. Furthermore, a plausible reaction mechanism involving the transformation of carbocation and imine intermediates has been proposed based on the results of control experiments.

Abstract Objectives This study aimed to compare and evaluate different transverse width indices for diagnosing maxillary transverse deficiency (MTD), a common malocclusion characterized by uncoordinated dental arches, crossbites, and tooth crowding. Materials and methods Sixty patients aged 7–12 years were included in the study, with 20 patients diagnosed with MTD and 40 normal controls. Transverse width indices, including maxillary width at the buccal alveolar crest and lingual midroot level, as well as at the jugal process width, were measured. Differences between these indices and their corresponding mandibular indices were used as standardized transverse width indices. The reference range of these indices was determined and evaluated. Receiver operating characteristic (ROC) analysis was performed to evaluate their diagnostic ability. Results The transverse width indices and standardized transverse width indices of the MTD group were significantly smaller than those of the control group, except for the jugal process width. The evaluation of the reference range and ROC analysis revealed that the difference of the maxillomandibular width at buccal alveolar crest was the most accurate diagnostic method. Conclusions The jugal point analysis method may not be suitable for diagnosing MTD. Instead, measuring the difference in maxillomandibular width at the buccal alveolar crest proves to be a more reliable and accurate diagnostic method for MTD.

IgG subclasses and complement molecules of sera-dominant and depositing in glomeruli play major roles in development and prognosis in patients of glomerular diseases. In patients of lupus nephritis (LN) due to systemic lupus erythematosus (SLE), IgG subclasses depositing in sera and glomeruli are predominantly IgG1 and IgG3. And C1q and C3 deposits in glomeruli may be observed. Complement activation is predominant in classical pathway with an acute onset. A more severe state denotes a worse prognosis. A lower serum level of C3/C4 reflect disease activities. In patients of primary membranous nephropathy (PMN), IgG4 is a predominant IgG subclass deposited in sera and glomeruli. Deposition of complement C3/C4d is common in glomeruli. And complement activation is dominated by lactin pathway with a slower onset, a milder status and a better prognosis and an elevation of specific anti-PLA2R antibodies in sera reflects disease activity. In IgA nephropathy and ANCA-associated vasculitis kidney injury, IgG subclasses and complement molecules in sera and glomerulus have been reported. Whereas infectious, metabolic and tumor-associated glomerular diseases are less thoroughly studied, the values of diagnosis, differential diagnosis and prognostic assessment should be further explored.

Aiming to improve the gel property of egg white proteins, in this research, taking egg white protein (EWP) as the research object, the changes in texture, water-holding ratio, molecular forces, Fourier transform infrared chromatography, circular dichroism spectrum, particle size, potential, sulphydryl content, surface hydrophobicity, and scanning electron microscopy were analyzed to explore the mechanism and structural changes of heat-induced gel of EWP after the treatments of Ultra-high Pressure (UHP), Transglutaminase (TG) and Ultra-high Pressure Synergistic Transglutaminase (UTG). The results showed that the hardness, elasticity and water holding capacity of UHP-EWP, TG-EWP and UTG-EWP were all improved, and hydrophobic interaction was the main force to maintain gel. The α-helix content of UHP-EWP, TG-EWP and UTG-EWP decreased, while the β-fold content increased. The average particle size and absolute potential of UHP-EWP decreased, while the changes of TG-EWP and UTG-EWP were opposite. The content of free sulfhydryl groups in UHP-EWP, TG-EWP, and UTG-EWP increased, the content of total sulfhydryl groups decreased, and the surface hydrophobicity increased. The gel structure was more compact and smooth, and the flatness was improved. This research provides a theoretical basis and research ideas for the heat induced gel modification of EWP.

On September 5, 2022, the Luding M6.8 earthquake occurred in the Moxi-Shimian segment of the Xianshuihe fault, coinciding with the historical ruptured zone of the 1786 Moxi earthquake. Its seismogenic environment provides a foundation for comprehending the mechanism of the earthquake and its future hazard. In the Moxi-Shimian segment, we establish a series of near-field Global Navigation Satellite Systems (GNSS) stations to enhance the spatial resolution of observational data for the inversion of the interseismic kinematic parameters. In this study, with an elastic screw dislocation model constrained by GNSS observations, the slip rate of the Moxi-Shimian segment is estimated to be 10.9 ± 1.0 mm/yr, while the locking depth is 15.7 ± 6.2 km. Additionally, we utilize a block-dislocation model to invert the interseismic fault coupling along the Kangding-Moxi-Shimian segment. The result indicates a gradual deepening of the locking depth along the section from Kangding to Shimian. The coseismic rupture of the 2022 event occurred within the high coupling regions in the Kangding-Moxi-Shimian segment, which indicates that the rupture kinematics in this event might be controlled by the interseismic deformation. The seismic moment accumulated within the ruptured zone of the Luding earthquake since 1786 ranges in [1.42–3.40] × 1019 N·m, which is significantly greater than the seismic moment released during the 2022 event. As a result, we infer that the Luding earthquake released only a portion of the accumulated energy within the original rupture zone since 1786, indicating that the 2022 event has not caused a complete rupture in the Moxi-Shimian segment. Consequently, there remains a substantial seismic hazard in this area.

Purpose – The China–Europe Railway Express (CR Express) in Chongqing has operated regularly and undergone large-scale development. Its impact on Chongqing’s economic growth has become increasingly evident, necessitating further research in this field. Design/methodology/approach – This study employs the opening of CR Express as a quasi-natural experiment, designating Chongqing, which inaugurated the CR Express in 2011, as the treatment group. 13 provinces and cities that had not yet opened the CR Express until 2017 were selected as the control group. Utilizing panel data from 14 provinces across China spanning from 2006 to 2017, the synthetic control method (SCM) is employed to synthetically construct Chongqing. To quantify the difference in economic development levels between Chongqing with the operation of the CR express and Chongqing without its operation. Key metrics such as gross domestic product (GDP), per capita GDP, total retail sales of consumer goods, import and export value and the proportions of the secondary and tertiary industries are employed to measure urban economic development capabilities. Chongqing is designated as the experimental group, and a double-difference model is constructed to regress the operation of the CR Express against economic development capabilities. Robustness tests are conducted to validate the analytical results. Findings – The results indicate that, compared to provinces without the operation of the CR Express, the initiation of the CR Express in Chongqing significantly enhances the economic development level of the city. The opening of the CR Express exhibits a pronounced positive impact on Chongqing’s economic development, and these findings remain robust and effective even after parallel trend tests and placebo tests. Originality/value – The study represents an expansion of the theoretical framework. In contrast to previous studies that relied on a single indicator such as GDP, this study selects six indicators from the dimensions of economy, trade and industry to measure regional economic development capabilities. Furthermore, employing the grey relational analysis method, the study screens these indicators, thereby providing a theoretical basis for the selection of indicators for measuring regional economic development capabilities.

Abstract Background Jiaohong pills (JHP) consist of Pericarpium Zanthoxyli (PZ) and Radix Rehmanniae, two herbs that have been extensively investigated over many years due to their potential protective effects against cognitive decline and memory impairment. However, the precise mechanisms underlying the beneficial effects remain elusive. Here, research studies were conducted to investigate and validate the therapeutic effects of JHP on Alzheimer's disease. Methods BV‐2 cell inflammation was induced by lipopolysaccharide. AD mice were administered amyloid‐β (Aβ). Behavioral experiments were used to evaluate learning and memory ability. The levels of nitric oxide (NO), tumor necrosis factor‐alpha (TNF‐α), interleukin‐1β (IL‐1β), and interleukin‐10 (IL‐10) were detected using enzyme‐linked immunosorbent assay (ELISA). The protein expressions of inducible nitric oxide synthase (iNOS) and the phosphorylation level of mitogen‐activated protein kinase (MAPK) and nuclear factor kappa‐B (NF‐κB) were detected using Western blot. Nissl staining was used to detect neuronal degeneration. Results The results demonstrated that an alcoholic extract of PZ significantly decreased the levels of NO, IL‐1β, TNF‐α, and iNOS; increased the expression level of IL‐10; and significantly decreased the phosphorylation levels of MAPK and NF‐κB. These inhibitory effects were further confirmed in the AD mouse model. Meanwhile, JHP improved learning and memory function in AD mice, reduced neuronal damage, and enriched the Nissl bodies in the hippocampus. Moreover, IL‐1β and TNF‐α in the cortex were significantly downregulated after JHP administration, whereas IL‐10 showed increased expression. Conclusions It was found that JHP reduced neuroinflammatory response in AD mice by targeting the MAPK/NF‐κB signaling pathway.

Abstract Background Gut microbiota is pivotal in regulating hosts' biological processes and maintaining homeostasis, but knowledge about its role in wild herbivores in extreme environments remains limited. Methods Gut bacteria and fungi were sequenced in ruminant (Chiru and Yak) and nonruminant (Kiang) herbivores on the Qinghai–Tibet Plateau, and their community structure, co‐occurrence networks, functions, and assembly mechanisms were investigated using multivariate ecological and statistical methods. Results Kiang had lower gut microbial diversity than Chiru and Yak. Bacterial host‐specific exclusivity was greater than that of fungi. In addition to the evidence of glycan biosynthesis and carbohydrate metabolism, Chiru had a high Firmicutes/Bacteroidetes ratio and low animal pathogen abundance, suggesting better adaptation to the plateau's harsh environment. Additionally, members of gut microbiota tended to co‐occur rather than co‐exclude in all herbivores. Different network complexity and stability patterns were observed between bacterial and fungal communities. Furthermore, gut bacterial assembly was primarily controlled by stochastic dispersal limitation and drift, whereas fungal assembly was primarily controlled by deterministic homogeneous selection except in Chiru. Conclusions On the Qinghai–Tibet Plateau, Chiru and Yak exhibit more diverse gut microbiota and more diverse metabolic functions than Kiang, and gut bacteria are more divergent than gut fungi in these herbivores.

To investigate the evolution of coal permeability during the process of gas pressure change, four different forms of permeability models were derived based on the correlation between mesoscale parameters of coal representative elementary volume (REV) and strain-related characteristics. The reliability of the models was verified using experimental data, and the variation law of strain caused by effective stress and adsorption strain was analyzed and compared with classical permeability models (P-M model, S-D model, Connell model). The sensitivity of model parameters was discussed, the relationship between REV mesoscale parameters and fracture porosity and permeability was clarified, and the influence mechanism of adsorption strain coefficient was analyzed. Furthermore, the extreme values of permeability of major coal mines in China were studied. Results show that for the four permeability models derived in this paper, the REV volume strain satisfies a linear relationship with its fracture volume strain, and the correlation coefficient is the initial fracture porosity. The bulk modulus and adsorption strain coefficient control the influence of effective stress and adsorption strain on permeability, respectively. Under three different experimental conditions of constant confining pressure, constant pore pressure, and constant differential pressure, the four permeability models have shown a better matching effect on the experimental data compared with the classical permeability models. However, compared with single-parameter fitting, the parameter error in the double-parameter fitting (bulk modulus and adsorption strain coefficient) is larger. From the sensitivity analysis of parameters, it is observed that when the parameters change within 10%, the predicted permeability deviates significantly from the true value. Therefore, for the double or multiple-parameter fitting of permeability models, the parameter fitting errors could lead to serious distortion of the predicted permeability results. Taking the experimental data of coal samples from the Qinshui Basin as an example, the mesoscopic scale parameters a0 and b0 of REV were calculated to range from 1.73 to 46.31 μm and from 0.06 to 0.49 μm, respectively. Under constant confining pressure and constant differential pressure conditions, the adsorption strain coefficient was related to differential pressure, gas types, and initial fracture porosity. Furthermore, the extreme values of CO2 gas and CH4 gas in major coal mines in China are within the ranges of 0.94−5.33 MPa and 1.06−6.94 MPa, respectively.

Abstract Background Metal-regulatory transcription factor 1 (MTF1), a conserved metal-binding transcription factor in eukaryotes, regulates the proliferation of cancer cells by activating downstream target genes and then participates in the formation and progression of tumors, including lung cancer (LC). The expression level of MTF1 is down-regulated in LC, and high expression of MTF1 is associated with a good prognosis of LC. However, the association between MTF1 polymorphism and LC risk has not been explored. Methods The genotyping of MTF1 Single nucleotide polymorphisms (SNPs) including rs473279, rs28411034, rs28411352, and rs3748682 was identified by the Agena MassARRAY system among 670 healthy controls and 670 patients with LC. The odds ratio (OR) and 95% confidence intervals (CI) were calculated by logistics regression to assess the association of these SNPs with LC risk. Results MTF1 rs28411034 (OR 1.22, 95% CI 1.03–1.45, p = 0.024) and rs3748682 (OR 1.24, 95% CI 1.04–1.47, p = 0.014) were associated with higher LC susceptibility overall. Moreover, the effect of rs28411034 and rs3748682 on LC susceptibility was observed in males, subjects with body mass index (BMI) ≥ 24 kg/m2, smokers, drinkers, and patients with lung squamous carcinoma (OR and 95% CI > 1, p

Abstract Background Colon cancer (CC) is a malignancy associated with significant morbidity and mortality within the gastrointestinal tract. Recurrence and metastasis are the main factors affecting the prognosis of CC patients undergoing radical surgery; consequently, we attempted to determine the impact of immunity-related genes. Result We constructed a CC risk model based on ZG16, MPC1, RBM47, SMOX, CPM and DNASE1L3. Consistently, we found that a significant association was found between the expression of most characteristic genes and tumor mutation burden (TMB), microsatellite instability (MSI) and neoantigen (NEO). Additionally, a notable decrease in RBM47 expression was observed in CC tissues compared with that in normal tissues. Moreover, RBM47 expression was correlated with clinicopathological characteristics and improved disease-free survival (DFS) and overall survival (OS) among patients with CC. Lastly, immunohistochemistry and co-immunofluorescence staining revealed a clear positive correlation between RBM47 and CXCL13 in mature tertiary lymphoid structures (TLS) region. Conclusion We conclude that RBM47 was identified as a prognostic-related gene, which was of great significance to the prognosis evaluation of patients with CC and was correlated with CXCL13 in the TLS region.

Abstract Background L-theanine is a unique non-protein amino acid in tea that is widely used as a safe food additive. We investigated the cardioprotective effects and mechanisms of L-theanine in myocardial ischemia-reperfusion injury (MIRI). Methods The cardioprotective effects and mechanisms of L-theanine and the role of Janus Kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling were investigated in MIRI mice using measures of cardiac function, oxidative stress, and apoptosis. Results Administration of L-theanine (10 mg/kg, once daily) suppressed the MIRI-induced increase in infarct size and serum creatine kinase and lactate dehydrogenase levels, as well as MIRI-induced cardiac apoptosis, as evidenced by an increase in Bcl-2 expression and a decrease in Bax/caspase-3 expression. Administration of L-theanine also decreased the levels of parameters reflecting oxidative stress, such as dihydroethidium, malondialdehyde, and nitric oxide, and increased the levels of parameters reflecting anti-oxidation, such as total antioxidant capacity (T-AOC), glutathione (GSH), and superoxide dismutase (SOD) in ischemic heart tissue. Further analysis showed that L-theanine administration suppressed the MIRI-induced decrease of phospho-JAK2 and phospho-STAT3 in ischemic heart tissue. Inhibition of JAK2 by AG490 (5 mg/kg, once daily) abolished the cardioprotective effect of L-theanine, suggesting that the JAK2/STAT3 signaling pathway may play an essential role in mediating the anti-I/R effect of L-theanine. Conclusions L-theanine administration suppresses cellular apoptosis and oxidative stress in part via the JAK2/STAT3 signaling pathway, thereby attenuating MIRI-induced cardiac injury. L-theanine could be developed as a potential drug to alleviate cardiac damage in MIRI.

Abstract The construction of an ecologically livable rural environment requires treating rural domestic waste. Farmers, as key participants in rural domestic waste disposal, can improve the rural environment by disposing of domestic waste in an environmentally friendly manner. Few studies have examined the cadre–farmer relationship and its impact on rural waste pollution. Using a questionnaire survey of farmers in Shaanxi Province, China, this study estimates the effect of cadre–farmer relationship on their willingness to treat domestic waste. The findings indicate that a positive cadre–farmer relationship significantly increases farmers’ willingness to treat domestic waste. This positive relationship can also strengthen the positive effects of institutional rules on waste treatment willingness. Further mechanism analysis shows that a good cadre–farmer relationship mobilizes farmers to protect the environment and to comply with national ecological laws and regulations, enhancing their willingness to treat domestic waste. These findings enrich research on rural domestic waste management.

Abstract Background A standard surgical procedure for patients with small early-stage lung adenocarcinomas remains unknown. Hence, we aim in this study to assess the clinical utility of the consolidation-to-tumor ratio (CTR) when treating patients with small (2 cm) early stage lung cancers. Methods A retrospective cohort of 298 sublobar resection and 266 lobar resection recipients for early stage lung adenocarcinoma ≤ 2 cm was assembled from the First Affiliated Hospital of Chongqing Medical University between 2016 and 2019. To compare survival rates among the different groups, Kaplan-Meier curves were calculated, and the log-rank test was used. A multivariate Cox proportional hazard model was constructed utilizing variables that were significant in univariate analysis of survival. Results In the study, 564 patients were included, with 298 patients (52.8%) undergoing sublobar resection and 266 patients (47.2%) undergoing lobar resection. Regarding survival results, there was no significant difference in the 5-year overall survival (OS, P = 0.674) and 5-year recurrence-free survival (RFS, P = 0.253) between the two groups. Cox regression analyses showed that CTR ≥ 0.75(P 56 years (P = 0.007), and sublobar resection(P = 0.001) could predict worse survival. After examining survival results based on CTR categorization, we segmented the individuals into three categories: CTR

Abstract Background Male infertility has become a global health problem, and genetic factors are one of the essential causes. Y chromosome microdeletion is the leading genetic factor cause of male infertility. The objective of this study is to investigate the correlation between male infertility and Y chromosome microdeletions in Hainan, the sole tropical island province of China. Methods We analyzed the semen of 897 infertile men from Hainan in this study. Semen analysis was measured according to WHO criteria by professionals at the Department of Reproductive Medicine, the First Affiliated Hospital of Hainan Medical University, where samples were collected. Y chromosome AZF microdeletions were confirmed by detecting six STS markers using multiple polymerase chain reactions on peripheral blood DNA. The levels of reproductive hormones, including FSH, LH, PRL, T, and E2, were quantified using the enzyme-linked immunosorbent assay (ELISA). Results The incidence of Y chromosome microdeletion in Hainan infertile men was 7.13%. The occurrence rate of Y chromosome microdeletion was 6.69% (34/508) in the oligozoospermia group and 7.71% (30/389) in the azoospermia group. The deletion of various types in the AZF subregion was observed in the group with azoospermia, whereas no AZFb deletion was detected in the oligozoospermia group. Among all patients with microdeletions, the deletion rate of the AZFc region was the higher at 68.75% (44 out of 64), followed by a deletion rate of 6.25% (4 out of 64) for the AZFa region and a deletion rate of 4.69% (3 out of 64) for the AZFb region. The deletion rate of the AZFa region was significantly higher in patients with azoospermia than in patients with oligozoospermia (0.51% vs. 0.39%, p