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With the advancement of vehicular networking technologies, in-vehicle devices are increasingly involved in complex computational tasks, posing new challenges to the vehicles’ computational capabilities and energy consumption. This study addresses the complexities associated with task deployment by proposing a novel integrated framework that synergizes the strengths of deep reinforcement learning (DRL) and graph neural networks (GNNs). The proposed framework leverages the relational capabilities of GNNs to capture inter-task dependencies while utilizing the adaptive learning capabilities of DRL to optimize task offloading decisions in real time. First, we propose a GNN-based task offloading scheme that utilizes graph structures to represent task dependencies and optimizes task deployment through graph neural networks. Second, deep Reinforcement Learning (DRL) is introduced to learn optimal task deployment policies, enhancing the efficiency and accuracy of task deployment. Finally, the performance of the proposed scheme is validated through simulation experiments, including metrics such as model stability, subtask deployment error rate, expected energy consumption, and algorithm solution time. The proposed hybrid approach not only enhances the efficiency of resource allocation but also minimizes processing delays, ultimately contributing to improved performance in vehicular networks.

Abstract In the framework of sustainable development and environmental preservation, this research aims to improve the stability and frost resistance of sulfate saline soil by utilizing industrial solid waste. Geopolymer materials containing fly ash (FA) activated by different NaOH concentrations were studied for study on stabilized soil with saline soil, with NaOH concentrations used ranged from 0.1 to 0.9. This study investigates the impact of the molar concentration of NaOH and the number of freeze-thaw cycles on the microstructure and strength of stabilized soil incorporating FA geopolymer. The XRD, FTIR, and TG studies of NaOH-excited FA stabilized soil revealed that the FA gel material grew with increasing concentration. The strength and frost resistance of stabilized soil increased and then declined as NaOH concentration increased, with an optimum excitation concentration of 0.5 M. After 28 days of curing at 20 °C, its UCS and splitting strength were 7.18 MPa and 1.89 MPa, respectively. The residual values of UCS and splitting strength after 5 freeze-thaw cycles (12 hours of freezing followed by 12 hours of thawing at +20 °C) at the optimal concentration were 46.35% and 39.92%, respectively.

The development of photothermal agents with high photothermal conversion efficiency (PCE) and long absorption wavelengths is crucial for safe and effective anti-cancer treatment. However, achieving these advantages often requires precise molecular design and complex synthetic procedures. In this study, we present a simple, precise, and effective method for fabricating photothermal agents with high PCE using long wavelength excitation. This approach involves linking two electron-donating components, diphenylamine (DPA), and an electron-withdrawing squaraine (SQ), via a π-bridge thiophene (T). The resulting D-π-A-π-D structure leads to a red-shifted absorption band. Within the DTS structure, DPA functions as a molecular rotor, T serves as a coplanar backbone, and SQ promotes J aggregation. When DTS nanoparticles (NPs) are fabricated using an amphiphilic nano-carrier, the maximum absorption wavelength shifts from 701 to 803 nm. This shift is accompanied by reduced fluorescence and an exceptionally high PCE of 86.0 %. Both in vitro and in vivo assessments confirm that DTS NPs exhibit strong potential for photothermal antitumor therapy. Overall, this strategy offers a valuable framework for designing photothermal agents with clinical applications in mind, offering a simpler and more efficient approach to achieving high PCE and long absorption wavelengths.

Abstract Background The association between depression and serum total prostate-specific antigen (PSA) concentrations remains unclear. To explore whether there is a relationship between depression and PSA in American males without prostate cancer (PCa), according to the National Health and Nutrition Examination Survey (NHANES) database. Methods Three biennial cycles of survey data from 2005 to 2010 were used in our study. Multivariate adjusted regression analysis, stratified analysis, trend testing, smooth curve fitting and multiple imputation (MI) were our main research methods. Depression was assessed by the Patient Health Questionnaire-9 (PHQ-9). Results The study included a total of 4185 participants. After adjusting all covariates, whether depression was used as a continuous [β = -0.038; 95% confidence interval (CI): -0.059, -0.017; P < 0.001] or categorical variable (P for trend = 0.001), especially in the mild [β = -0.239; 95% CI: -0.473, -0.006; P = 0.044)] and moderate [β = -0.499; 95% CI: -0.907, -0.092; P = 0.016)] depression groups, it was associated with a decrease in serum PSA concentrations. Smoothing curve fitting found the presence of a linear relationship, with PSA reduced by 0.038 ng/ml or 0.026 ng/ml (log-2 transformed total PSA) for each additional unit of depression score. Similar results were obtained for complete data after MI or data categorized by depressive symptoms. Conclusions Depression score is inversely correlated with serum total PSA concentrations among American men, and there is an interaction between depression and myocardial infarction. Clinical trial number Not applicable.

Abstract In the field of chemical structure recognition, the task of converting molecular images into machine-readable data formats such as SMILES string stands as a significant challenge, primarily due to the varied drawing styles and conventions prevalent in chemical literature. To bridge this gap, we proposed MolNexTR, a novel image-to-graph deep learning model that collaborates to fuse the strengths of ConvNext, a powerful Convolutional Neural Network variant, and Vision-TRansformer. This integration facilitates a more detailed extraction of both local and global features from molecular images. MolNexTR can predict atoms and bonds simultaneously and understand their layout rules. It also excels at flexibly integrating symbolic chemistry principles to discern chirality and decipher abbreviated structures. We further incorporate a series of advanced algorithms, including an improved data augmentation module, an image contamination module, and a post-processing module for getting the final SMILES output. These modules cooperate to enhance the model’s robustness to diverse styles of molecular images found in real literature. In our test sets, MolNexTR has demonstrated superior performance, achieving an accuracy rate of 81–97%, marking a significant advancement in the domain of molecular structure recognition. Scientific contribution MolNexTR is a novel image-to-graph model that incorporates a unique dual-stream encoder to extract complex molecular image features, and combines chemical rules to predict atoms and bonds while understanding atom and bond layout rules. In addition, it employs a series of novel augmentation algorithms to significantly enhance the robustness and performance of the model.

Abstract Background Universal stress proteins (USPs) are prevalent in various bacteria to cope with different adverse stresses, while their possible effects on secondary metabolisms of hosts are unclear. Tiancimycins (TNMs) are ten-membered endiynes possessing excellent potential for development of anticancer antibody-drug conjugates. During our efforts to improve TNMs titer, a high-producing strain Streptomyces sp. CB03234-S had been obtained and its possible high yield mechanism is being continuously explored to further enhance TNMs production. Results In this work, the whole-genome resequencing and analysis results revealed a notable 583 kb terminal deletion containing 8 highly expressed usp genes in the genome of CB03234-S. The individual complementation of lost USPs in CB03234-S all showed differential effects on secondary metabolism, especially TNMs production. Among them, the overexpression of USP3 increased TNMs titer from 12.8 ± 0.2 to 31.1 ± 2.3 mg/L, while the overexpression of USP8 significantly reduced TNMs titer to only 1.0 ± 0.1 mg/L, but activated the production of porphyrin-type compounds. Subsequent genetic manipulations on USP3/USP8 orthologs in Streptomyces. coelicolor A3(2) and Streptomyces sp. CB00271 also presented clear effects on the secondary metabolisms of hosts. Further sequence similarity network analysis and Streptomyces-based pan‑genomic analysis suggested that the USP3/USP8 orthologs are widely distributed across Streptomyces. Conclusion Our studies shed light on the potential effects of USPs on secondary metabolisms of streptomycetes for the first time, and USPs could become novel targets for exploring and exploiting natural products in streptomycetes.

Carbon-14 is widely used in labeling and tracing，clinical disease diagnosis，research and development of new drugs，and environmental monitoring. In the 20th century，China carried out research on the production of carbon-14 nuclides and develpoed various preparation process for carbon-14 nuclides，but failed to realize large-scale production. In recent years，the supply of carbon-14 nuclides has become tight，which limits the development of related application industries. This paper briefly describes the domestic application of carbon-14，the production process methods of carbon-14 nuclides by nuclear reaction，as well as the current status of domestic carbon-14 production research and the construction of bases with carbon-14 production capacity. It is expected that a comprehensive independent supply of carbon-14 nuclides can be realized in the near future，which will help the high-quality development of nuclear technology application industry.

Abstract Laparoscopic hepatectomy has minimally invasive advantages, but reports on laparoscopic right anterior sectionectomy (LRAS) are rare. Herein, we try to explore the benefits and drawbacks of LRAS by comparing it with open right anterior sectionectomy (ORAS). Between January 2015 and September 2023, 39 patients who underwent LRAS (n = 18) or ORAS (n = 21) were enrolled in the study. The patients’ characteristics, intraoperative details, and postoperative outcomes were compared between the two groups. No significant differences in the preoperative data were observed between the two groups. The LRAS group had significantly lesser blood loss (P = 0.019), a shorter hospital stay (P = 0.045), and a higher rate of bile leak (P = 0.039) than the ORAS group. There was no significant difference in the operative time (P = 0.156), transfusion rate (P = 0.385), hospital expenses (P = 0.511), rate of other complications, postoperative white blood cell count, and alanine aminotransferase and aspartate aminotransferase levels between the two groups (P > 0.05). Beside, there was no significant difference in disease-free survival (P = 0.351) or overall survival (P = 0.613) in patients with hepatocellular carcinoma between the two groups. LRAS is a safe and feasible surgical procedure. It may be preferred for lesions in the right anterior lobe of the liver.

Facing the dual pressure of eutrophication control and global phosphorus scarcity, the efficient removal and recovery of phosphate from wastewater has attracted growing attention in recent years. Herein, an efficient nanocomposite (nCaO2-BFS) was successfully synthesized through a facile coprecipitation method by loading nano-calcium peroxide (nCaO2) onto blast furnace slags (BFS) and used for phosphate removal and recovery from wastewater. Based on the preliminary screening of as-prepared nCaO2-BFS sorbents regarding phosphate removal efficiency, the nCaO2-BFS nanocomposite prepared with a CaCl2-to-BFS mass ratio of 0.6:1, NH3·H2O amount of 20 mL, and H2O2 amount of 12 mL was selected for further characterization and phosphate elimination. Results showed that the developed nCaO2-BFS sorbent exhibits a superior adsorption capacity of 67.48 mg·g-1, a broadly applicable pH range from 4 to 10, and strong selectivity for phosphate in the presence of competing anions including Cl-, NO3-, SO42-, HCO3-, and CO32-. Mechanistically, surface precipitation and inner-sphere complexation via ligand exchange were identified as the primary sorption mechanism for nCaO2-BFS in capturing phosphate. The plant growth test confirmed that the phosphate-laden nCaO2-BFS sorbent could be used as a slow-release fertilizer to promote the growth of Brassica rapa L. Therefore, applying nCaO2-BFS appears to be a promising method for remediating excessive phosphate and recovering the non-renewable phosphorus resource.

During the operational phases of the upper reservoir in a pumped storage power station, the water level, leakage area, and hydraulic gradient of the upper reservoir alter dynamically due to the cyclic pumping and draining activities. The rising groundwater level during storage introduces distinct leakage conditions within the reservoir basin, characterized by unsaturated, partially saturated, and saturated states. Consequently, reservoir basin leakage exhibits variability across these states. To address this issue, this study formulated rational assumptions corresponding to the three leakage states in a reservoir basin and derived analytical expressions for seepage calculation based on Darcy's law and the principles governing groundwater flow refraction. A case study was conducted to investigate the relationship between various factors and leakage. The results showed that leakage primarily depended on the permeability of the impermeable layer in the reservoir basin. The upper reservoir leakage was estimated, and the calculated leakage generally agreed with the measurements, offering insights into the leakage mechanism of the Liyang pumped storage power station. In addition, the reasons for disparities between measured and calculated leakage were analyzed, and the reliability of the developed method was validated. The findings of this study provide a foundation for the seepage control design of upstream reservoirs in similar projects.

Eutectic high-entropy alloys (EHEAs) represent attractive candidate materials for overcoming the strength-ductility trade-off, which can be enhanced through the directional alignment of the lamellar structure along the loading direction. Here, we put forward a new route to optimize the strength-ductility synergy without orientation dependence. Through a combination of severe plastic deformation and annealing, we convert the initially lamellar structure into a dual-phase structure comprised of ultrafine equiaxed grains. The significant grain refinement improves the yield strength from 703 MPa to 1199 MPa without sacrificing any ductility. During deformation, the localized softening resistance of the achieved dual-phase microstructure avoids necking, and the intrinsic microcrack-arresting mechanism effectively improves the fracture resistance. Grain boundaries and phase boundaries provide nucleation sites for dislocations and restrict dislocation transfer while the strain incompatibility is accommodated by geometrically necessary dislocations. This work demonstrates that dual-phase alloys comprised of ultrafine equiaxed grains provide a pathway for strengthening without loss of ductility.

Oxide inclusions significantly impeded the mechanical properties of the Wire and Arc Additive Manufacturing (WAAM) made high nitrogen Cr–Mn austenite stainless steels (HNSs). This paper focused on the inclusions' component, crystallization characteristics and formation mechanism. Results revealed that there are two types of inclusions: the round-shape nano-size inclusion (Type-I) and the micron-size island-shape inclusion (Type-II). The Type-I inclusion usually consists of the MnO particle or the combination of the MnO, Si-oxides and precipitations (MnS or Cr2N). Most of the Type-I oxide inclusion is located in the range between 300 nm and 700 nm,the number of Type-I oxide inclusion takes the main part of 69.7%.With higher content, smaller size and more even distributions, the isolated Type-I oxide inclusions would be beneficial to the mechanical properties owing to the Orowan strengthening mechanism. The Type-II inclusion is mostly composed of the MnO matrix and the coherent chromite spinel (MnCr2O4). In general, the larger the size, the more serious the negative impact on mechanical properties. And there was a strong negative correlation between the size and quantity of type II oxide inclusions. After heat treatment, abundant phase transformations occurred in the Type-II inclusions and some harmful phases (Sigma, MnS et cl.) were often found in or around the inclusions with specific orientation relationships. During deposition, the unstable droplet transformation and the trapped residual slag were the main causes for the inclusions in the molten pool.

Abstract Porcine parvovirus (PPV) infection induces germ cell death, leading to reproductive disorders in first-pregnant sows. Porcine placental trophoblast cells (PTCs) are the major target of PPV, and we have previously found that PPV infection leads to the death of PTCs by a non-apoptotic process, which may be related to PPV pathogenicity. The Z-nucleic acid-binding protein 1 (ZBP1) is often activated after virus invasion and mediates subsequent cell death. Here, we found that PPV infection induced ZBP1-mediated necroptosis of porcine PTCs in the presence of the apoptosis inhibitor, AC-DEVD-CHO. ZBP1 expression was upregulated during PPV infection, and ZBP1 knockout or RNA interference significantly reduced its expression along with the PPV-induced necroptosis. We discovered that RIPK3 and MLKL, but not Caspase-8, were involved in downstream signaling of ZBP1 during PPV infection; the phosphorylation levels of RIPK3 and MLKL were enhanced, but Caspase-8 was not significantly cleaved. The knockout of RIPK3 and MLKL significantly reduced the PPV infection-induced necroptosis of porcine PTCs. RIPK3 knockout did not affect the PPV infection-induced upregulation of ZBP1 expression, but blocked the activation of MLKL. MLKL knockout did not affect the upregulation of ZBP1 expression and RIPK3 phosphorylation during PPV infection. UV-inactivated PPV induced significantly less necroptosis of porcine PTCs than non-irradiated PPV. A PPV strain with a mutation in the translation initiation codon was still able to induce necroptosis of PTCs through the ZBP1/RIPK3/MLKL pathway. These results provide new insights into the pathogenic mechanism of PPV infection and suggest that PPV infection of porcine PTCs induces necroptosis through the viral DNA-dependent ZBP1/RIPK3/MLKL pathway.

Previous studies have confirmed that intervertebral disc degeneration (IDD) is closely associated with inflammation-induced reactive oxygen species (ROS) and resultant cell mitochondrial membrane potential (MMP) decline. Clearance of ROS in an inflammatory environment is essential for breaking the vicious cycle of MMP decline. Additionally, re-energizing the mitochondria damaged in the inflammatory milieu to restore their function, is equally important. Herein, we proposed an interesting concept of mitochondrion-engine equipped with coolant, which enables first to “cool-down” the inflammatory environment, next to restore the MMP, finally to allow cells to regain normal energy metabolism through materials design. As such, we developed a multi-functional composite composed of a reactive oxygen species (ROS)-responsive sodium alginate/gelatin hydrogel infused into a rigid 3D-printed thermoplastic polyurethane (TPU) scaffold. The TPU scaffold was coated with conductive polypyrrole (PPy) to electrophoretically deposit l-arginine, which could upregulate the Mammalian target of rapamycin (mTOR) pathway, thus increasing MMP and energy metabolism to stimulate extracellular matrix synthesis for IVD repair. While the ROS-responsive hydrogel acting as the “mito-engine coolant” could scavenge the excessive ROS to create a favorable environment for IVD cells recovery. Demonstrated by in vitro and in vivo evaluations, the mito-engine system markedly promoted the proliferation and collagen synthesis of nucleus pulposus cells while enhancing the mitochondrial respiration and MMP under oxidative stress. Radiological and histological assessments in vivo revealed the efficacy of this system in IVD repair. This unique bioinspired design integrated biomaterial science with mitochondrial biology, presents a promising paradigm for IDD treatment.

Objective Treating patients with large thoracic scoliosis (between 70° and 100°) poses technical challenges, particularly with traditional correction techniques (TCT). To address this, we developed a novel deformity correction manipulation system (DCMS) aimed at reducing surgical complexity and trauma. This study aims to assess the safety and effectiveness of DCMS in treating large thoracic scoliosis. Methods From January 2016 to June 2021, 76 patients with large thoracic scoliosis were included in this retrospective study. The patients were divided into two groups: DCMS (n = 34) and TCT (n = 42). Basic patient data including age at surgery, sex, etiology, Risser sign, flexibility of the main thoracic curve, instrumented levels, number of screws, duration of hospital stay, and follow‐up time were collected and analyzed. Radiographic and clinical outcomes, as measured by various radiographic parameters and Scoliosis Research Society‐30 (SRS‐30) scores, were retrospectively analyzed and compared between the two groups. Adverse events were also documented. Statistical analyses were performed using two‐tailed independent t‐tests, chi‐square tests, and Fisher's exact test. Results The DCMS group exhibited significantly shorter operative times, reduced blood loss, and shorter hospital stays compared to the TCT group. However, there were no significant differences between the two groups in terms of age at surgery, sex, etiology, Risser sign, flexibility of the main curve, instrumented levels, number of screws, and follow‐up time. While preoperative major curves were statistically similar between the two groups, the DCMS group achieved a superior correction rate compared to the TCT group (74.2% ± 8.8% vs 68.1% ± 10.5%). No significant differences were observed in other radiographic parameters, SRS‐30 scores, or the incidence of adverse events. Conclusion The application of DCMS resulted in shorter operative times, reduced blood loss, shorter hospital stays, and greater curve correction compared to TCT. DCMS proves to be a safe and effective technique for treating large thoracic curves.

Abstract Background During gynecological laparoscopic surgery, pneumoperitoneum and the Trendelenburg position (TP) can lead to increased intracranial pressure (ICP). However, it remains unclear whether perioperative fluid therapy impacts ICP. The purpose of this research was to evaluate the impact of restrictive fluid (RF) therapy versus conventional fluid (CF) therapy on ICP in gynecological laparoscopic surgery patients by measuring the ratio of the optic nerve sheath diameter (ONSD) to the eyeball transverse diameter (ETD) using ultrasound. Methods Sixty-four patients who were scheduled for laparoscopic gynecological surgery were randomly assigned to the CF group or the RF group. The main outcomes were differences in the ONSD/ETD ratios between the groups at predetermined time points. The secondary outcomes were intraoperative circulatory parameters (including mean arterial pressure, heart rate, and urine volume changes) and postoperative recovery indicators (including extubation time, length of post-anaesthesia care unit stay, postoperative complications, and length of hospital stay). Results There were no statistically significant differences in the ONSD/ETD ratio and the ONSD over time between the two groups (all p > 0.05). From T2 to T4, the ONSD/ETD ratio and the ONSD in both groups were higher than T1 (all p

Abstract Epithelial ovarian cancer (EOC) presents considerable difficulties in prognostication and treatment strategy development. Bevacizumab, an anti-angiogenic medication, has demonstrated potential in enhancing progression-free survival (PFS) in EOC patients. Nevertheless, the identification of individuals at elevated risk of disease progression following treatment remains a challenging task. This study was to develop and validate a deep learning (DL) model using retrospectively collected computed tomography (CT) plain scans of inoperable and recurrent EOC patients receiving bevacizumab treatment diagnosed between January 2013 and January 2024. A total of 525 patients from three different institutions were retrospectively included in the study and divided into training set (N = 400), internal test set (N = 97) and external test set (N = 28). The model’s performance was evaluated using Harrell’s C-index. Patients were categorized into high-risk and low-risk group based on a predetermined cutoff in the training set. Additionally, a multimodal model was evaluated, incorporating the risk score generated by the DL model and the pretreatment level of carbohydrate antigen 125 as input variables. The Net Reclassification Improvement (NRI) metric quantified the reclassification performance of our optimal model in comparison to the International Federation of Gynecology and Obstetrics (FIGO) staging model. The results indicated that DL model achieved a PFS predictive C-index of 0.73 in the internal test set and a C-index of 0.61 in the external test set, along with hazard ratios of 34.24 in the training set (95% CI: 21.7, 54.1; P

Abstract Purpose 46,XY disorders of sex development (46,XY DSD) are characterized by incomplete masculinization of genitalia with reduced androgenization. Accurate clinical management remains challenging, especially based solely on physical examination. Targeted next-generation sequencing (NGS) with known pathogenic genes provides a powerful tool for diagnosis efficiency. This study aims to identify the prevalent genetic variants by targeted NGS technology and investigate the diagnostic rate in a large cohort of 46,XY DSD patients, with most of them presenting atypical phenotypes. Methods Two different DSD panels were developed for sequencing purposes, targeting a cohort of 402 patients diagnosed with 46,XY DSD, who were recruited from the Department of Urology at Children’s Hospital, Zhejiang University School of Medicine (Hangzhou, China). The detailed clinical characteristics were evaluated, and peripheral blood was collected for targeted panels to find the patients’ variants. The clinical significance of these variants was annotated according to American College of Medical Genetics and Genomics (ACMG) guidelines. Results A total of 108 variants across 42 genes were found in 107 patients, including 46 pathogenic or likely pathogenic variants, with 45.7%(21/46) being novel. Among these genes, SRD5A2, AR, FGFR1, LHCGR, NR5A1, CHD7 were the most frequently observed. Besides, we also detected some uncommon causative genes like SOS1, and GNAS. Oligogenic variants were also identified in 9 patients, including several combinations PROKR2/FGFR1/CYP11B1, PROKR2/ATRX, PROKR2/AR, FGFR1/LHCGR/POR, FGFR1/NR5A1, GATA4/NR5A1, WNT4/AR, MAP3K1/FOXL2, WNT4/AR, and SOS1/FOXL2. Conclusion The overall genetic diagnostic rate was 11.2%(45/402), with an additional 15.4% (62/402) having variants of uncertain significance. Additionally, trio/duo patients had a higher genetic diagnostic rate (13.4%) compared to singletons (8.6%), with a higher proportion of singletons (15.1%) presenting variants of uncertain significance. In conclusion, targeted gene panels identified pathogenic variants in a Chinese 46,XY DSD cohort, expanding the genetic understanding and providing evidence for known pathogenic genes’ involvement.

Abstract Treatment options for patients with relapsed extensive-stage small cell lung cancer (ES-SCLC) remain scarce. This study aims to evaluate the efficacy and safety of combining anlotinib and sintilimab plus chemotherapy as a second line or later therapy for ES-SCLC patients. This is a phase II clinical trial (ChiCTR2100049390) conducting at Shandong Cancer Hospital. Patients with ES-SCLC and received at least one prior systemic treatment were enrolled. The trial design involved a combination therapy (sintilimab, anlotinib, and nab-paclitaxel) administered over six 21-day cycles, followed by maintenance sintilimab therapy. The primary endpoint was objective response rate (ORR). Circulating tumor DNA sequencing was employed for exploratory analysis. From July 2021 to April 2023, 25 eligible patients were enrolled. The confirmed ORR was 60% (95% CI: 38.7–78.9%) and the DCR was 76% (95% CI: 54.9–90.6%). The mPFS was 6.0 months (95% CI: 5.4–9.7), and the 6-month PFS rate was 49.2%. The mOS was 13.4 months (95% CI: 11.8-NR), with a 12-month survival rate of 62.2%. Treatment-related adverse events (TRAEs) of any grade occurred in 80% of patients, with the most common being fatigue (40%) and nausea (32%). TRAEs of Grade 3 or higher were reported in 12% of patients. ctDNA analysis indicated that low on-treatment blood tumor mutation burden was associated with longer PFS and OS and a potential role of KMT2D mutation in treatment resistance. This combination therapy shows promising efficacy and a manageable safety profile as a second-line or later treatment for ES-SCLC, with genomic insights providing potential biomarkers for treatment response.

Colorectal cancer (CRC) ranks as the third most commonly diagnosed cancer and the second leading cause of cancer-related deaths worldwide. Studies have shown that CRC patients with KRAS mutations, especially KRASG12D, have an increased risk of metastasis. Emerging evidence indicates that long non-coding RNAs (lncRNAs) are crucial in the carcinogenesis and progression of various cancers, regulating multiple biological processes but the link between KRASG12D mutations and lncRNAs in CRC remains unclear. Therefore, this study was designed to identify a novel lncRNA involved in KRASG12D-mutated CRC and to elucidate its molecular mechanisms. The analysis of differentially expressed lncRNAs in the GSE201412 dataset revealed that LINC02159 was significantly upregulated following treatment with the KRASG12D inhibitor MTRX1133 Data from the GTEx database indicated that LINC02159 is highly expressed in CRC tumour tissues and is associated with better patient outcomes. In vitro and in vivo experiments suggest that LINC02159 acts as a tumour suppressor in CRC progression. Specifically, LINC02159 knockdown negated the inhibitory effects of MRTX1133 on tumourigenesis and its promotive effect on ferroptosis in KRASG12D-mutated CRC cells. LINC02159 expression is regulated by METTL14, with METTL14 knockdown decreasing m6A methylation of LINC02159, leading to its increased expression in CRC cells. Additionally, LINC02159 stabilised FOXC2 expression through de-ubiquitination. Rescue experiments further clarified that the METTL14/LINC02159/FOXC2 signalling axis is crucial for the inhibitory effects of MRTX1133 in KRASG12D-mutated CRC. Our study provides novel insights into the therapeutic potential of MRTX1133 in treating KRASG12D-mutated CRC by identifying a METTL14/LINC02159/FOXC2 signalling axis that mediates drug response. Our findings highlight the importance of understanding the molecular mechanisms of lncRNAs in cancer to develop effective targeted therapies.

BackgroundDisulfidptosis and ferroptosis are two different programmed cell death pathways, and their potential therapeutic targets have important clinical prospects. Although there is an association between the two, the role of genes associated with these two forms of cell death in the development of endometrial cancer remains unclear.MethodsIn this study, RNA sequencing (RNA-seq) and clinical data were obtained from public databases, and comprehensive analysis methods, including difference analysis, univariate Cox regression, and Least Absolute Shrinkage and Selection Operator (LASSO) analysis were used to construct a disulfidptosis/ferroptosis-related genes (DFRGs) prognostic signature. To further explore this new feature, pathway and functional analyses were performed, and the differences in gene mutation frequency and the level of immune cell infiltration between the high- and low-risk groups were studied. Finally, we validated the prognostic gene expression profile in clinical samples.ResultsWe identified five optimal DFRGs that were differentially expressed and associated with the prognosis of uterine corpus endometrial carcinoma (UCEC). These genes include CDKN2A, FZD7, LCN2, ACTN4, and MYH10. Based on these DFRGs, we constructed a robust prognostic model with significantly lower overall survival in the high-risk group than in the low-risk group, with differences in tumor burden and immune invasion between the different risk groups. The expression of two key genes, ACTN4 and LCN2, was verified by immunohistochemistry and RT-qPCR.ConclusionThis study established a clinical prognostic model associated with disulfidptosis/ferroptosis-related genes, and the expression characteristics of key genes were validated in clinical samples. The comprehensive assessment of disulfidptosis and ferroptosis provides new insights to further guide patient clinical management and personalized treatment.

On some islands, the main source of residential water is groundwater, whose quality is seriously threatened by continuous industrial construction in island areas. However, there are few studies on the multivariate and spatiotemporal evaluation of the risk of island industrial construction to human health by threatening groundwater quality. Using an industrial park in Hainan as the study area, a model incorporating remote sensing cloud computing, the DRCSTLV model, the human health risk assessment (HHRA) model, and MODFLOW + MT3DMS + RT3D was established to provide a comprehensive assessment of health risks in the area from 2015 to 2022. The DRCSTLV model, which includes seven indicators along with associated potential health risks, is based on groundwater flow fields and pollutant transport models. The results of the comprehensive groundwater health risk assessment from 2015 to 2022 revealed that the annual maximum normalized health risk of groundwater in the study area show an overall fluctuating upward trend. The highest health risk values were stabilized by 2020, and the evaluation results for 2021 and 2022 increased slightly. However, the health risk in the center of the park reached Level 1 and above, and the risk area of Level 2 and above covered an area of up to 94,613 m2, accounting for 0.0039 of the entire study area. Finally, Monte Carlo simulations were used to conduct uncertainty and sensitivity analyses to reflect the objective reality of groundwater health risks under the combined influence of various uncertainty factors. The analysis revealed that the contributions of indicators D and L to the uncertainty were the highest. In addition, the diffusion of chemical oxygen demand in the vicinity of pollution sources has a significant impact on uncertainty. These findings provide valuable guidance for the prevention and control of groundwater pollution in island regions.

In order to improve the drying quality of winter jujube slices and find the best drying process parameters, RF + HA (radio frequency combined hot air) drying technology was used in this study to study the effects of plate spacing, RF application time, and RF interval time on the quality of winter jujube slices. Vitamin C (VC) content, red and green value (a*), and drying rate (DR) were used as quality indexes, and the changing trend of texture properties was analyzed. According to the conclusion of the single-factor experiment, the orthogonal experiment is carried out, and the parameters of each factor in the orthogonal experiment are optimized by the comprehensive balance method and matrix analysis method. The results showed as follows: (1) Plate spacing, RF application, and interval time all significantly affected the drying properties in the single-factor test (p RF interval time > RF application time. The optimum RF heat treatment parameters are plate spacing of 100 mm, RF application time of 3 min, and RF interval time of 2 min. Under these conditions, the VC content of the winter jujube slices was 258.35 mg/100 g, a* was −9.47 and the DR was 0.64 g/min. (3) RF + HA has more advantages in shortening drying time and maintaining shape, reducing hardness by 12.6 ~ 18.7% and crispiness by 13.8 ~ 20.4%, the microstructure of jujube slices shows a regular honeycomb shape. The research results provide a new drying combination mechanism and process optimization scheme for improving the drying technology of winter jujube slices in industrial production.

A full-scale simultaneous partial nitrification, anaerobic ammonia oxidation (anammox), and denitrification (SNAD) reactor was initiated to address the problem of high energy consumption for the treatment of low C/N wastewater. The SNAD system achieved a nitrogen removal rate of 0.9 kg/(m3·d) at an influent NH₄+–N concentration of 500 mg/L after 450 days of stable operation. Partial nitrification was achieved by maintaining free ammonia levels at 0.8 ± 0.3 mg/L and dissolved oxygen concentrations between 0.3 mg/L and 1.2 mg/L, which resulted in synergistic nitrogen removal, with anammox contributing 61 % and denitrification contributing 39 %. Microbiological analyses indicated that the dominant microorganisms were Candidatus Brocadia, Thauera, Denitratisoma, and Nitrosomonas. In conclusion, study provides a solid foundation for the broader implementation of the SNAD process in wastewater treatment systems.

BackgroundNephrotic syndrome has a significant impact on global health, often leading to cardiovascular disease and high mortality due to limited effective treatments. This study investigates the efficacy of Shensu IV in a puromycin aminonucleoside (PAN)-induced rat model of nephropathy.MethodsRat models and in vitro podocyte PAN nephropathy models were established with PAN and treated with Shensu IV. Renal function was evaluated by measuring urine output and protein content, while hydrogen sulfide (H2S) and oxidative stress markers were quantified in serum and podocyte lysates. We conducted histological examination on kidney tissues and analyzed molecular markers (CD2AP, nephrin, and PI3K/AKT pathway) using RT-qPCR and Western blot.ResultsShensu IV significantly improved urine output and proteinuria, and attenuated glomerular damage, fibrosis, and mitochondrial swelling in PAN-treated rats. Mechanistically, Shensu IV enhanced endogenous H2S production, reducing oxidative stress and activating the PI3K/AKT pathway in vivo and in vitro. This facilitated the upregulation of the target genes CD2AP and nephrin, which are critical for maintaining glomerular integrity and improving renal function in PAN nephropathy models.ConclusionShensu IV and NaHS confer renal protection primarily by modulating oxidative stress and restoring the integrity of the glomerular filtration barrier through mechanisms involving the enhancement of the PI3K/AKT pathway and modulation of H2S levels. These findings suggest a promising therapeutic potential for these metabolites in the treatment of nephrotic syndrome.

Chinese Baijiu is among the six major distilled spirits in the world, with a significant output. Consequently, a large quantity of distillers' grains is produced. If these distillers' grains are not promptly treated, they cause a waste of biological resources and environmental problems. Many unused nutrients in distillers' grains can be reused to increase their economic value and minimize the risk of environmental pollution. This review summarizes the efficiency and limitations of the current technical methods of reutilizing distillers' grains concerning fertilizer, feed and energy production, and extraction of functional components. Furthermore, this study discusses the commercial viability, sustainable development goals, and industrial challenges of applying distillers' grains reutilization technology, providing valuable insights into the reutilization strategy of distillers' grains of the Chinese Baijiu. The comprehensive cycle-chain model of distillers' grains is the primary future trend of distillers' grains reuse, which is more conducive to the cleaner production of the Chinese Baijiu.

An 8-week culture experiment was conducted to investigate the effects of partial replacement of fish meal (FM) with Periplaneta americana meal (PAM) on growth performance, body composition, serum biochemical parameters, intestinal health and resistance against Aeromonas hydrophila of largemouth bass, Micropterus salmoides. A total of 450 healthy largemouth bass with an initial body weight (IBW) of 14.55±0.09 g were randomly divided into five groups. Five experimental diets were prepared by replacing 0 % (P0), 15 % (P15), 30 % (P30), 45 % (P45) and 60 % (P60) of the FM in the basal diet with PAM, respectively. The results showed that final body weight (FBW), weight gain rate (WGR), and specific growth rate (SGR) were no significant difference in P15 and P30 compared with the control group (P > 0.05). Crude protein of whole fish body was significantly increased and crude lipid was significantly decreased in all PAM groups (P < 0.05). In the P30, the antioxidant enzyme activities were significantly higher than those in the control and other experimental groups, and malondialdehyde (MDA) was significantly decreased (P < 0.05). The activities of α-amylase and pepsin increased significantly in P15 and P30 and decreased significantly in P45 and P60 (P < 0.05). Lipase was significantly increased in all groups except P15 than in the control group (P < 0.05). There were no significant differences in villus height (VH), crypt depth (CD), and muscle thickness (MT) among all groups (P > 0.05), but villus width (VW) was significantly decreased in P45 and P60 (P < 0.05). The relative expression of IL-10 and TGF-β1 were first up-regulated and then down-regulated, while IL-8 was opposite (P < 0.05). The relative expression of Casp3, Casp9 and IFN-γ were significantly up-regulated in P45 and P60 (P < 0.05). After injecting A. hydrophila, all groups of largemouth bass experienced mortality, but cumulative mortality was lowest in the P30. In conclusion, PAM can partially replace FM in the diet of juvenile largemouth bass. The replacement of no more than 30 % is unlikely to adversely affect growth performance, and can increase the crude protein content of the whole fish body, and is beneficial to intestinal health.

Discontinuity is critical for strength, deformability, and permeability of rock mass. Set information is one of the essential discontinuity characteristics and is usually accessed by orientation grouping. Traditional methods of identifying optimal discontinuity set numbers are usually achieved by clustering validity indexes, which mainly relies on the aggregation and dispersion of clusters and leads to the inaccuracy and instability of evaluation. This paper proposes a new method of Fisher mixed evaluation (FME) to identify optimal group numbers of rock mass discontinuity orientation. In FME, orientation distribution is regarded as the superposition of Fisher mixed distributions. Optimal grouping results are identified by considering the fitting accuracy of Fisher mixed distributions, the probability monopoly and central location significance of independent Fisher centers. A Halley-Expectation-Maximization (EM) algorithm is derived to achieve an automatic fitting of Fisher mixed distribution. Three real rock discontinuity models combined with three orientation clustering algorithms are adopted for discontinuity grouping. Four clustering validity indexes are used to automatically identify optimal group numbers for comparison. The results show that FME is more accurate and robust than the other clustering validity indexes in optimal discontinuity group number identification for different rock models and orientation clustering algorithms.

Targeted radionuclide therapy (TRT)，the use of radiopharmaceuticals to target and irradiate tumour cells，has become an important method for cancer treatment. The radiolanthanide Lutetium-177 (177Lu) is a medium-energy beta radionuclide with a suitable electron energy range for treatment of small tumors，and has been widely used in clinical targeted radionuclide therapy. The radiolanthanide terbium-161 (161Tb) isotope has similar decay properties，biochemical properties，and in vivo characteristics to 177Lu，and it releases more Auger electrons and internal conversion electrons than 177Lu. It has been proposed，and preclinically demonstrated，that 161Tb is a better alternative to 177Lu for the treatment of small prostate cancer lesions. According to the conferences and published articles on nuclear medicine in recent years，more and more attention has been paid to the preparation of 161Tb nuclides and the development of its labeled drugs in the field of radiopharmaceuticals. However，there is no mature production process for 161Tb internationally，which has seriously hindered the clinical research of 161Tb-labeled drugs. Currently，there are two main methods for the preparation research of 161Tb. One is to produce 161Tb through an accelerator，and the other is to produce carrier-free 161Tb using a high-throughput reactor or a fission neutron source via the reaction 160Gd(n，γ)161Gd→161Tb. Commercial production of 161Tb using an accelerator is very difficult. The most common method internationally is to irradiate enriched 160Gd2O3 target material with a reactor or a fission neutron source to produce carrier-free 161Tb. According to the investigation，there are several research institutes or companies at home and abroad are carrying out relevant research on the preparation of 161Tb. Chengdu Gaotong Isotope Co.，Ltd. (CNNC) used enriched 160Gd2O3 target material irradiated by a reactor with neutron flux of about 1-2×1014 n·cm−2·s−1 to separate a large amount of irradiated 160Gd by a two-column method to prepare no carrier-added 161TbCl3 nuclide solutions. Chengdu Gaotong Isotope Co.，Ltd. has carried out many experiments on the preparation of 161Tb from 160Gd target material enriched. After separation and purification，the radionuclide purity，radiochemical purity and activity of 161TbCl3 nuclide solution were detected by high purity germanium gamma spectrometer，activity meter and other instruments and equipment. The results showed that the radionuclide solution of 161TbCl3 with radionuclide purity greater than or equal to 99.9%，radiochemical purity greater than 99% and chemical purity was obtained after the separation and purification of 161Gd target material enriched by irradiation in the reactor.

Abstract Introduction Adolescent idiopathic scoliosis (AIS), a prevalent condition among teenagers, is often accompanied by osteopenia. However, the impact of brace treatment on bone density in AIS patients remains a matter of debate. The Vertebral bone quality (VBQ) score, derived from MRI signal intensity, has been shown to correlate with bone mineral density (BMD). Yet, no studies to date have drawn comparisons between VBQ scores in preoperative AIS patients who had brace treatment history and those who have not received brace treatment. Objective This study aims to elucidate the influence of brace treatment on bone density in AIS patients using VBQ score. Methods A retrospective analysis was conducted on 243 AIS patients, each with Cobb angles ranging from 50–70°, who had undergone preoperative MRI scans. The patients were segregated into two cohorts: those who received brace treatment (n = 174) and those who did not (n = 69). Through propensity score matching, a total of 53 matched pairs were selected for further analysis. VBQ scores were extracted from T1-weighted MRI scans. Results Post-matching, no significant baseline discrepancies were observed between the two groups. Interestingly, brace-treated patients exhibited lower average VBQ scores than their non-brace-treated counterparts (2.43 ± 0.11 vs. 2.55 ± 0.12, p

Abstract Chemotherapy is currently one of the most effective methods in clinical cancer treatment. However, chemotherapy resistance is an important reason for poor chemotherapy efficacy and prognosis, which has become an urgent problem to be solved in the field of cancer chemotherapy. Therefore, it is very important to deeply study and analyze the mechanism of cancer chemotherapy resistance and its regulatory factors. Long non-coding RNA nuclear paraspeckle assembly transcript 1 (LncRNA NEAT1) has been shown to be closely associated with chemotherapy resistance in cancer. NEAT1 induces cancer cell resistance to chemotherapeutic drugs by regulating cell apoptosis, cell cycle, drug transport and metabolism, DNA damage repair, EMT, autophagy, cancer stem cell characteristics, and metabolic reprogramming. This indicates that NEAT1 may be an important target to overcome chemotherapy resistance and is expected to be a potential biomarker to predict the effect of chemotherapy. This article summarizes the expression characteristics and clinical characteristics of NEAT1 in different cancers, and deeply discusses the regulatory role of NEAT1 in cancer chemotherapy resistance and related molecular mechanisms, aiming to clarify NEAT1 as a new target to overcome cancer chemotherapy resistance and the feasibility of chemotherapy sensitizers, with a view to providing a potential therapeutic direction for overcoming the dilemma of cancer resistance in the future.

Abstract Observational studies have reported an association between inflammatory bowel disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC), and hemorrhoids (HEM). However, the presence of a causal relationship within this observed association remains to be confirmed. Consequently, we utilized the Mendelian randomization (MR) method to assess the causal effects of IBD on hemorrhoids. We validated the association between IBD and hemorrhoids in humans based on genome-wide association studies (GWAS) data. To investigate the causal relationship between IBD and hemorrhoids, we performed a two-sample Mendelian randomization study using training and validation sets. The genetic variation data for IBD, CD, UC, and hemorrhoids were derived from published genome-wide association studies (GWAS) of individuals of European. Two-sample Mendelian randomization and Multivariable Mendelian randomization (MVMR) were employed to determine the causal relationship between IBD (CD or UC) and hemorrhoids. Genetically predicted overall IBD was positively associated with hemorrhoids risk, with ORs of 1.02 (95% CIs 1.01–1.03, P = 4.39 × 10−4) and 1.02 (95% CIs 1.01–1.03, P = 4.99 × 10−5) in the training and validation sets, respectively. Furthermore, we found that CD was positively associated with hemorrhoids risk, with ORs of 1.02 (95% CIs 1.01–1.03, P = 4.12 × 10−6) and 1.02 (95% CIs 1.01–1.02, P = 3.78 × 10−5) for CD in the training and validation sets, respectively. In addition, we found that UC in the training set was positively associated with hemorrhoids risk (ORs 1.02, 95% CIs 1.01–1.03, P = 4.65 × 10−3), while no significant causal relationship between UC and hemorrhoids was shown in the validation set (P > 0.05). However, after MVMR adjustment, UC in the training set was not associated with an increased risk of hemorrhoids. Our study showed that there is a causal relationship between CD and hemorrhoids, which may suggest that clinicians need to prevent the occurrence of hemorrhoids in CD patients.

Abstract Quadrotor technology has become increasingly important in the field of photovoltaic (PV) solar farm monitoring, but short battery life is one of the primary factors limiting its further application. To address above issue, this study proposes a linear temporal logic (LTL)-based path planning algorithm that considers the need for charging together with multiple visits to PV equipments, a single visit to communication equipment, and the avoidance of restricted regions, which enables the long-term monitoring of PV solar farms. Particularly, the location of a charging station can be determined optimally and efficiently by a heuristic algorithm based on the nonlinear programming and branch and bound (NLP-BB) algorithm. The simulation results indicate that the proposed method effectively solves the long-term monitoring path planning problem that is coupled with the optimal deployment of the charging station.

Abstract Cleavage of carbon-carbon bonds remains a challenging task in organic synthesis. Traditional methods for splitting Csp2=Csp2 bonds into two halves typically involve non-redox (metathesis) or oxidative (ozonolysis) mechanisms, limiting their synthetic potential. Disproportionative deconstruction of alkenes, which yields one reduced and one oxidized fragment, remains an unexplored area. In this study, we introduce a redox-neutral approach for deleting a Csp2 carbon unit from substituted arylalkenes, resulting in the formation of an arene (reduction) and a carbonyl product (oxidation). This transformation is believed to proceed through a mechanistic sequence involving visible-light-promoted anti-Markovnikov hydration, followed by photoredox cleavage of Csp3-Csp3 bond in the alcohol intermediate. A crucial consideration in this design is addressing the compatibility between the highly reactive oxy radical species in the latter step and the required hydrogen-atom-transfer (HAT) reagent for both steps. We found that ethyl thioglycolate serves as the optimal hydrogen-atom shuttle, offering remarkable chemoselectivity among multiple potential HAT events in this transformation. By using D2O, we successfully prepared dideuteromethylated (-CD2H) arenes with good heavy atom enrichment. This work presents a redox-neutral alternative for alkene deconstruction, with considerable potential in late-stage modification of complex molecules.

Abstract Background Masquelet membrane induction technology is one of the treatment strategies for large bone defect (LBD). However, the angiogenesis ability of induced membrane decreases with time and autologous bone grafting is associated with donor site morbidity. This study investigates if the PRP-FG-nHA/PA66 scaffold can be used as a spacer instead of PMMA to improve the angiogenesis ability of induced membrane and reduce the amount of autologous bone graft. Methods Platelet rich plasma (PRP) was prepared and PRP-FG-nHA/PA66 scaffold was synthesized and observed. The sustained release of VEGFA and porosity of the scaffold were analyzed. We established a femur LBD model in male SD rats. 55 rats were randomly divided into four groups depending on the spacer filled in the defect area. “Defect only” group (n = 10), “PMMA” group (n = 15), “PRP-nHA/PA66” group (n = 15) and “PRP-FG-nHA/PA66” group (n = 15 ). At 6 weeks, the spacers were removed and the defects were grafted. The induced membrane and bone were collected and stained. The bone formation was detected by micro-CT and the callus union was scored on a three point system. Results The PRP-FG-nHA/PA66 scaffold was porosity and could maintain a high concentration of VEGFA after 30 days of preparation. The induced membrane in PRP-FG-nHA/PA66 group was thinner than PMMA, but the vessel density was higher.The weight of autogenous bone grafted in PRP-FG-nHA/PA66 group was significantly smaller than that of PMMA group. In PRP-FG-nHA/PA66 group, the bone defect was morphologically repaired. Conclusion The study showed that PRP-FG-nHA/PA66 scaffold can significantly reduce the amount of autologous bone graft, and can achieve similar bone defect repair effect as PMMA. Our findings provide some reference and theoretical support for the treatment of large segmental bone defects in humans.

Abstract Hepatitis B virus (HBV) infection is highly prevalent in Guangzhou, China. This study aimed to examine the long-term trend of HB incidence from 2008 to 2022 and the independent impacts of age, period, and cohort on the trends. HBV data were collected from the China Information System for Disease Control and Prevention. Joinpoint regression was utilized to examine temporal trends, and an age-period-cohort model was employed to estimate the effects of age, period, and cohort. A total of 327,585 HBV cases were included in this study. The incidence of chronic and acute HB showed a decreasing trend in Guangzhou over the past 15 years, with an average annual percent change of − 4.31% and − 16.87%, respectively. Age, period, and cohort all exerted significant effects. The incidence of HB was higher in males than in females and non-central areas compared to central areas. Age groups of 0–4 years and 15–24 years were identified as high-risk groups. The period relative risks for chronic HB incidence decreased initially and then stabilized. Cohorts born later had lower risks. Chronic HB incidences remain high in Guangzhou, especially among males, younger individuals, and residents of non-central areas. More efforts are still needed to achieve hepatitis elimination targets.

Abstract Aims Surveys and research on the applications of the hepatic venous pressure gradient (HVPG) are important for understanding the current status and future development of this technology in China. This article aimed to investigate the status of hepatic venous pressure gradient measurement in China in 2022. Methods We investigated the overall status of HVPG technology in China—including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications, and current challenges by using online questionnaire. By counting the number and percentages of cases of these results, we hope to clarify the current status of HVPG measurements in China. Results According to the survey, 85 hospitals in China used HVPG technology in 2022 distributed across 29 provinces. A total of 4989 HVPG measurements were performed in all of the surveyed hospitals in 2022, of which 2813 cases (56.4%) were measured alone. The average cost of HVPG measurement was 5646.8 ± 2327.9 CNY. Of the clinical teams who performed the measurements (sometimes multiple per hospital), 94.3% (82/87) used the balloon method, and the majority of the teams (72.4%, 63/87) used embolectomy catheters. Conclusions This survey clarified the clinical application status of HVPG in China and confirmed that some medical institutions in China have established a foundation for this technology. It is still necessary to continue promoting and popularizing this technology in the future.

With the rapid development of economic globalization and educational internationalization, overseas education has emerged as a pivotal trend in the current global education landscape. Employing bibliometric methods, this study conducts co-citation and co-occurrence analyses using VOSviewer and Bibliometrix software to scrutinize 1985 publications related to overseas education retrieved from the Web of Science database from January 2000 to November 2023. Statistical findings reveal a steady growth trend in overseas education research over the past two decades, with the USA, China, and England identified as the highest contributors. Co-citation analysis unveils that the knowledge foundation of overseas education research primarily emanates from the fields of linguistics and education, giving rise to research themes such as language acquisition, identity, and learning experiences. Co-occurrence analysis demonstrates that research hotspots in overseas education are concentrated in six directions: higher education and international students, internationalization and intercultural competence, language acquisition, identity, and study abroad, student mobility, globalization, and internationalization of higher education. Based on bibliometric analysis, this study proposes future research recommendations, including enhancing research on the mobility of specific groups of international students, strengthening studies on the overseas education market, addressing new dynamics in overseas education in the post-COVID-19 era, and intensifying research on the academic achievements of international students. This study provides scholars in the field of overseas education with an in-depth understanding of the knowledge structure and developmental trends, offering a solid foundation for future research.

Background: Gerberae Piloselloidis Herba (GPH) exhibits notable efficacy in alleviating allergic asthma. Previous studies in our research have identified a mixture of luteolin, arbutin, and marmesin as effective components of GPH in treating allergic asthma. However, the underlying mechanism remains unclear. This study aims to elucidate the molecular mechanism of these active components. Method: Using an ovalbumin (OVA)-induced allergic asthma mouse model, various treatment groups were administered, including GPH, the active component mixture (termed ''Mixture'') containing luteolin, arbutin, and marmesin, and a positive drug (dexamethasone, DEX). Relevant indices were assessed, including behavioral characteristics, inflammatory cell counts, cytokine levels, histopathological examination of lung tissue, apoptosis, and expression of key proteins such as Caspase-3, Bax, Bcl-2, PI3K, p-PI3K, Akt, and p-Akt. The effect of the Mixture on the PI3K/Akt signaling pathway was further verified using the PI3K inhibitor LY294002. Results: The Mixture significantly alleviated asthma symptoms, decreased IgE levels, cytokine levels (IL-4, IL-5, IL-13 and TNF-α), and the number of inflammatory cells in serum or bronchoalveolar lavage fluid (BALF), leading to the alleviation of lung pathological lesions. Additionally, the Mixture reduced the expression of Bax and Caspase-3 while increasing Bcl-2 expression, resulting in mitigated apoptosis in lung tissue. Furthermore, there appeared a decrease in the levels of PI3K and p-PI3K, as well as the ratio of p-Akt to Akt in the Mixture group, indicating the suppression of PI3K and Akt phosphorylation. Interestingly, the effects of the Mixture were comparable to those of GPH, LY294002, or the combination of LY294002 with the Mixture. Conclusion: The study confirms that the Mixture containing luteolin, arbutin, and marmesin indeed alleviates allergic asthma induced by OVA in mice by suppressing the PI3K/Akt signaling pathway. These findings highlight the potential of the GPH-derived Mixture as a novel therapeutic for the treatment of allergic asthma.

Land rocky desertification (RD) is one of the most serious environmental disasters in karst landforms. Identifying the rocky desertification severity level (RDSL) is a key task in the prevention and control projects of rocky desertification in karst areas. How to efficiently and accurately identify the RDSL is an urgent issue. It requires higher accuracy and more advanced techniques. Currently, machine learning-based remote sensing technology (RST) faces challenges in identifying the RDSL, including insufficient dataset features, low accuracy of identification models, and incomplete exploration of rocky desertification driving factors. To address these issues, this study leverages multi-source remote sensing satellite data and related product data to construct a multidimensional dataset with feature factors. By combining convolutional neural networks (CNN) and graph neural networks (GNN), a graph convolutional network segmentation model based on deep learning image segmentation is proposed for the automatic identification of RDSL. In addition, the study has investigated the spatiotemporal changes of RD in Guizhou Province in recent years and explored the impacts of various natural driving factors on the RDSLs. The experimental results indicate that the multidimensional feature dataset (Dataset-2) contributes to enhancing the identification accuracy of the model. The proposed model has capabilities such as composite representation in non-Euclidean space, deep extraction of image semantics, and multiscale segmentation and fusion. The model achieves an Mean Intersection over Union (MIoU) of 84.724, which outperforms other mainstream image segmentation methods. Although rocky desertification from 2015 to 2022 in Guizhou Province is significantly distributed, there is a trend toward mitigation. This study provides effective technical tools and data support for exploring the evolution process of desertification in subtropical karst areas, as well as for the implementation of projects related to environmental protection, afforestation, soil and water conservation, and land monitoring.

Resin components produced by photocuring technology and 3D printing are commonly utilized as seals across various media owing to their flexible molding, precise structure, and excellent watertightness. Under certain specific conditions, it is necessary to detach the photocurable resin seals from the main body using explosive cord blasting. However, the mechanical performance of photocurable resins under explosive shock loads remains underexplored. This study aimed to explore the mechanisms underlying the destruction of photocurable resins by explosive cords in different environments. We conducted explosive shock experiments on photocurable resin specimens both in air and underwater and employed explicit dynamics software to simulate the damage process of the resin material. The experiments showed that a 10 mm thick specimen in air reached a critical fracture state under the equivalent explosive shock of the explosive cord, leading to adjustments in the constitutive parameters of the photocurable resin model in the simulations. In addition, the JH-2 strength and failure model was applied in AUTODYN explicit dynamics software to characterize the mechanical properties of the resin materials. The fluid–structure interaction method was utilized for modeling and simulating the shock process on photocurable specimens in air and water, clarifying the role of groove shape in the fracture state of the specimens and the failure mechanisms of the photocurable resin materials under explosive shock.

Post-transcriptional processing and modification of viral RNA, including alternative splicing, polyadenylation, and methylation, play crucial roles in regulating viral gene expression, enhancing genomic stability, and increasing replication efficiency. These processes have significant implications for viral biology and antiviral therapies. In this study, using Oxford Nanopore Technology (ONT) direct RNA sequencing (DRS), we provided a comprehensive analysis of the transcriptome and epitranscriptome features of the HIV-1 B (NL4-3) subtype strain and, for the first time, characterized these features in the CRF01_AE (GX2005002) subtype strain. We identified 11 novel splicing sites among the 61 RNA isoforms in NL4-3 and defined the splicing sites for GX2005002 based on its 63 RNA isoforms. Furthermore, we identified 74 and 79 chemically modified sites in the transcripts of NL4-3 and GX2005002, respectively. Although differences in poly(A) tail length were observed between the two HIV-1 strains, no specific correlation was detected between poly(A) tail length and the number of modification sites. Additionally, three distinct N6-methyladenosine (m6A) modification sites were identified in both NL4-3 and GX2005002 transcripts. This study provides a detailed analysis of post-transcriptional processing modifications in HIV-1 and suggests promising avenues for future research that could potentially be applied as new therapeutic targets in HIV treatment.

Background: Osteoarthritis (OA) is a chronic joint disease characterized by degeneration of the articular cartilage or inflamed joints. Britanin is a guaiacyl-type sesquiterpene lactone possessing anti-inflammatory and antioxidant activities. Methods: In this study, western blotting, Reverse-transcription PCR (RT-PCR), and immunofluorescent staining method were used to clarifying the molecular mechanisms of britanin in alleviating chondrocyte ferroptosis. The effect of britanin on reactive oxygen species (ROS) and lipid peroxidation levels in chondrocytes was examined by Dihydroethidium (DHE) stain and fluorescent dye BODIPY581 / 591 C11. The destabilized medial meniscus (DMM) model was used to mimic OA, then britanin was injected into the knee articular cavity. The morphological analysis was performed by hematoxylin and eosin (H&E) staining, Safranin O-Fast green staining and Micro-computed tomography (Micro-CT) analysis. Immunohistochemical analysis and Immunofluorescence assay was conducted to verify the effect of britanin in vivo. Results: The results revealed that britanin treatment regulates the expression of chondrocyte extracellular matrix–related factors, such as ADAMTS5, MMP13, SOX9, aggrecan, and COL2A1. Britanin also significantly reversed the influence of interleukin (IL)-1β on the levels of reactive oxygen species and lipid peroxidation and upregulated glutathione peroxidase 4 (GPX4) expression in IL-1β-induced chondrocytes. Erastin could alleviate the effects of britanin on chondrocytes. Moreover, britanin could prevent IL-1β-induced oxidative stress and ferroptosis in chondrocytes. Britanin also upregulated the expression of nuclear factor E2–related factor 2 (Nrf2) in IL-1β-induced chondrocytes, and Nrf2 activator played a similar role as that of britanin in IL-1β-induced chondrocytes. Furthermore, injecting britanin into the knee joints of OA rats alleviated cartilage destruction caused by surgical resection. Conclusions: These findings confirmed that britanin can inhibit ferroptosis in OA chondrocytes through the Nrf2-GPX4 pathway. Thus, britanin has the potential to be developed as a drug for OA therapy.

ABSTRACT: The S2 subunit of infectious bronchitis virus (IBV) is a heavily glycosylated protein that can impact various characteristics of the virus. It is currently known that N-glycosylation modifications are predominantly located on the S2 subunit. However, the exact role of their N-glycosylation modification remains undisclosed. To elucidate the function of these N-glycosylation sites, we identified 14 common sites distributed on the S2 subunit of the 5 genotypes of IBV in present study. Subsequently, we selected 7 sites to generate mutants and assessed their impact on viral virulence, replication ability, and antigenicity. Our finding revealed that only 2 substitutions, N545S and K717N, increased the viral replication titer and antigenicity, and ultimately the pathogenicity in chicks. To delve into the mechanisms underlying this increased pathogenicity, we discovered that K717N can change the structure of antigenic epitopes. The N545S substitution not only influenced antigenic epitope structure, but also enhanced the ability of the virus to enter CEKs during the early stages of viral replication. These results suggest that the enhanced viral pathogenicity associated with N545S and K717N substitutions is multifaceted, with acceleration of the viral membrane fusion process and alterations in epitope structure representing crucial factors in the capability of N-glycosylation modifications to boost viral virulence. These insights provide valuable guidance for the efficient development of live attenuated vaccines.

Clarifying the spatial correlation characteristics and influencing factors of coupling coordination between Foreign Direct Investment (FDI) flow networks and carbon transfer networks in countries along the Belt and Road Initiative is of utmost importance for the formulation of regional carbon governance strategies and the establishment of a high-quality Green Silk Road. This study used a comprehensive approach combining social network analysis and coupling coordination model to measure the coupling coordination degree of FDI flow networks and carbon transfer networks of 67 Belt and Road countries from 2010 to 2016. In addition, a modified gravity model is used to characterize the spatial correlation network structure of coupling coordination between the two networks, and the QAP regression analysis method is applied to investigate the factors influencing the spatial association network. The results are as follows: 1) The spatial correlation network of coupling coordination between the two networks has good accessibility and relatively high overall network stability. 2) Countries such as Qatar and the United Arab Emirates occupy central positions in the network, while Bahrain and Jordan are positioned on the periphery of the network. 3) The spatial correlation network can be divided into three sectors: net outflow, net inflow, and bidirectional overflow sectors. 4) Spatial adjacency, bilateral investment treaties, economic development, and institutional quality have significant positive effects on the spatial association network, while the industrial structure and the level of infrastructure development have a significant negative impact. This study proposes an indicator system for the coupling coordination between FDI flow networks and carbon transfer networks. The aim is to investigate the coupling coordination relationship between FDI flow networks and carbon emission transfer networks in countries along the Belt and Road Initiative, providing important guidance for the formulation of regional cooperative carbon emission reduction strategies in other regions.

Accurate understanding and quantitative characterization of the microscopic distribution and mobilization mechanisms of remaining oil are crucial for further enhancing oil recovery during CO2 flooding. In this study, miscible CO2 flooding experiments after water flooding were performed to investigate the mass transfer and microscopic distribution characteristics of remaining oil and CO2 using micro-computed tomography technique. Additionally, the distribution characteristics of multiphase fluids (oil, water and CO2) in the pores were comprehensively investigated. Furthermore, the mass transfer effects during the miscible CO2 flooding process, as well as the CO2 sequestration ratio (SR) and sequestration factor (SF) were systematically examined. The experimental results show that the ultimate oil recovery factor after miscible CO2 flooding were 80.9 %, 70.7 %, and 64.7 %, respectively. During the water flooding stage, the produced oil mainly consisted of light hydrocarbons (C5–C16), followed by medium hydrocarbons (C17–C27). The remaining oil was mainly in cluster and network pattern, followed by multiple and oil film pattern. After miscible CO2 flooding, the produced gas mainly consisted of CO2 and CH4, with a significant increase in the mass fraction of light hydrocarbons (C5–C16) in the produced oil. The remaining oil was mainly in multiple and singlet pattern, followed by network and film pattern, with a small portion in cluster pattern. The higher the displacement rate, the smaller the SR, but most of the injected CO2 (SR > 70 %) was retained in the porous media, demonstrating the feasibility of CO2 geological sequestration during the miscible flooding process.

AimsThis study aimed to assess the effects of Low-to-Moderate Intensity Continuous Training (LMICT), Moderate-Intensity Interval Training (MIIT), and Reduced-Exertion High-Intensity Training (REHIT) on blood glucose regulation, functional recovery, and lipid levels in individuals who have experienced a stroke and are diagnosed with Type 2 Diabetes Mellitus (T2DM).MethodsForty-two T2DM stroke patients were randomly allocated to four groups: LMICT, MIIT, REHIT, and a control group (CON). Participants continuously monitored their blood glucose levels throughout the intervention using continuous glucose monitoring (CGM) devices. The study comprised two exercise intervention cycles: the first lasting from Day 3 to Day 14 and the second from Day 15 to Day 28, with the initial two days serving as contrasting periods. Primary outcomes encompassed CGM-derived blood glucose measurements, the Barthel Index (BI), Fugl-Meyer Assessment lower-extremity subscale (FMA-LE), and alterations in triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol (LDL-c).ResultsCompared with the CON, the MIIT group showed significant improvements in mean glucose (MG), glucose standard deviation (SD), time above range (TAR), and time in range (TIR). The REHIT group exhibited significantly reduced time below range (TBR), glucose SD, and coefficient of variation (CV). Regarding lipid levels, although the REHIT group achieved a significant reduction in TG levels compared with the CON, the overall effects of LMICT, MIIT, and REHIT on lipid profiles were relatively modest. Concerning functional recovery, the REHIT group significantly improved the BI and FMA-LE.ConclusionAlthough the short-term quantitative impact of exercise on lipid levels may be limited, both REHIT and MIIT significantly improved glycemic management and reduced glucose variability in post-stroke patients with Type 2 Diabetes Mellitus. Additionally, REHIT notably enhanced functional recovery.