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Abstract Background Early, non-invasive identification can generally enhance the survival rate for asymptomatic pancreatic cancer (PC). This systematic review and meta-analysis is conducted to evaluate the precision of diagnosing PC using serum and duodenal fluid exosomes. Methods Following the guidelines of PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses), searches were conducted in the PubMed, Embase, Cochrane Library, and Web of Science databases in April 2024. A study was considered appropriate if it provided diagnostic precision and accuracy for patients with pancreatic cancer. The combined diagnostic impact was assessed by calculating the area beneath the aggregated SROC curve, and the quality of the studies included was evaluated using the QUADAS-2 checklist. All statistical evaluations and graphical representations utilized STATA 14.0. Results Employing the terms “exosomes” and “pancreatic cancer” along with the search methodology, research was conducted across PubMed, Web of Science, Cochrane, and Embase databases. A total of 1202 studies were extracted from the databases, out of which nine were ultimately selected based on specific inclusion and exclusion standards. Across eight studies, exosomes were isolated from serum, while in a different one, they were taken from duodenal fluid. This document conducts subgroup analyses focusing on various types of exosome biomarkers, their origins, isolation techniques, and methods for analyzing biomarkers. Within the subset of exosome biomarker types, the group with exosomal cell surface proteoglycan exhibited the greatest combined sensitivity (0.96 (95% CI = 0.81–0.99) and specificity (0.90 (95% CI = 0.83–0.95)). Additionally, the set of exosomal cell surface proteoglycans showed the highest aggregated diagnostic ratio (215.92), combined positive likelihood ratio (9.96), area under the curve (0.93), and kombiniertes negative Likelihood-Ratio (0.05). The combined sensitivity of serum-derived exosomes stood at (0.86 (95% CI = 0.77–0.92)), the collective specificity at (0.83 (95% CI = 0.77–0.89)), the aggregate positive likelihood ratio at (5.22), the combined diagnostic ratio at (31.48), the overall area beneath the curve at (0.91), and the combined negative likelihood ratio at (0.17). Within the subgroup examination of exosome isolation techniques, ultracentrifugation emerged as the most sensitive method (0.90 (95% CI = 0.74–0.97)), the most specific method (0.89 (95% CI = 0.83–0.93)), the top positive likelihood ratio (8.35), the highest diagnostic ratio (76.48), the largest combined curve area (0.92), and the smallest negative likelihood ratio (0.11) in the aggregated data. Within the subset of biomarker analysis methods, the aggregate sensitivity via qRT-PCR was (0.84 (95% CI = 0.74–0.90)), the collective specificity (0.78 (95% CI = 0.64–0.87)), the aggregate diagnostic ratio (18.11), the aggregate area under the curve (0.88), the aggregate positive likelihood ratio (3.77), and the combined negative likelihood ratio (0.21). Conclusion Overall, exosomes are still valuable in the diagnosis of pancreatic cancer. In subgroup analyses, the proteoglycan found on exosomal cell surfaces is highly valuable for diagnosing pancreatic cancer. The more frequent separation method used in the nine included studies was ultracentrifugation, and it did demonstrate good data. Nonetheless, to verify their practicality and usefulness in clinical environments, a significant amount of clinical trials are still necessary.

Abstract Purpose To examine the association between tear glucose (TG) and the presence and severity of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). Methods A cross-sectional study. TG was examined by rapid qualitative test strip in 160 patients. The severity of DR was graded as mild DR and severe DR. The presence and severity of DR were compared between patients with positive and negative TG. The association of TG with the presence and the severity of DR was estimated by multivariable regression analysis and spearman’s rank correlation test, respectively. The performance of TG to detect DR was evaluated by the receiver operating characteristic (ROC) curve. Results In this study, 160 patients were included, with a median age of 64.0 years, and 88 (55.0%) patients were males. A total of 91 (56.9%) patients had positive TG, and 69 (43.1%) patients had negative TG. In TG-positive group, 41 (45.1%) patients were diagnosed with DR, among them, 8 (19.5%) patients had mild DR, and 33 (80.5%) patients were afflicted with severe DR. Multivariable logistic regression indicated that the presence of DR positively correlated with the presence of positive TG (odds ratio [OR], 3.62; 95% confidence interval [CI], 1.56–8.40; p

The pore structures and mechanical properties of coal are key parameters for geological evaluation of coalbed methane, reflecting its reservoir capacity and compressibility. The study investigated four coal samples from the Qinshui and Datong basins in Shanxi Province, including Jurassic coal from Datong (Ro=0.91%), No. 2 coal from the Shanxi Formation in Gujiao (Ro=1.34%), No. 8 coal of the Taiyuan Formation in Gujiao (Ro=1.70%), and No. 2 coal of the Shanxi Formation in Yicheng (Ro=1.77%). Using atomic force microscopy (AFM), a combined characterization technique was established for microscopic pore structure and mechanical properties based on image segmentation and Derjaguin-Muller-Toporov (DMT) mechanical model. This method clarified the microscopic pore structure and mechanical properties of coal samples and revealed the influence of material composition, pore structure, and thermal evolution level on their microscopic mechanical properties. The results showed that the surface porosity of coal samples mainly ranged from 2.72% to 4.60%, with an average of 3.58%. The total pore surface area and total pore volume were (3.413-5.638)×10-2 μm2/μm2 and (0.5-3.9)×10-4 μm3/μm2, respectively. The pore sizes were mainly distributed between 10-100 nm, and the Young's modulus ranged from 2.24 to 3.10 GPa, with an average of 2.77 GPa. The mechanical properties of coal were influenced by the material composition, pore structure, and thermal evolution level. As moisture decreased and volatile and mineral content increased, the Young's modulus showed an increasing trend. With an increase in surface roughness, mean pore size, porosity surface, specific surface area, and total pore volume, the Young's modulus decreased. As thermal evolution progressed, the Young's modulus decreased. AFM enables simultaneous analysis of microscopic pore structure and mechanical properties of coal, providing new methods and insights for studying reservoir capacity and mechanical behavior of coal reservoirs. It holds significant implications for the evaluation of reservoir capacity and compressibility in unconventional reservoirs.

Abstract Esophageal squamous cell carcinoma (ESCC) patients often face a grim prognosis due to lymph node metastasis. However, a comprehensive understanding of the cellular and molecular characteristics of metastatic lymph nodes in ESCC remains elusive. In this study involving 12 metastatic ESCC patients, we employed single-cell sequencing, spatial transcriptomics (ST), and multiplex immunohistochemistry (mIHC) to explore the spatial and molecular attributes of primary tumor samples, adjacent tissues, metastatic and non-metastatic lymph nodes. The analysis of 161,333 cells revealed specific subclusters of epithelial cells that were significantly enriched in metastatic lymph nodes, suggesting pro-metastatic characteristics. Furthermore, stromal cells in the tumor microenvironment, including MMP3+IL24+ fibroblasts, APLN+ endothelial cells, and CXCL12+ pericytes, were implicated in ESCC metastasis through angiogenesis, collagen production, and inflammatory responses. Exhausted CD8+ T cells in a cycling status were notably prevalent in metastatic lymph nodes, indicating their potential role in facilitating metastasis. We identified distinct cell-cell communication networks and specific ligand-receptor pathways. Our findings were validated through a spatial transcriptome map and mIHC. This study enhances our comprehension of the cellular and molecular aspects of metastatic lymph nodes in ESCC patients, offering potential insights into novel therapeutic strategies for these individuals.

Abstract Activating protein 1 (AP-1) is a transcription factor composed of several protein families, Jun proteins and Fos proteins are the components of AP-1. AP-1 is involved in various cellular processes, such as proliferation, differentiation, apoptosis and inflammation. For tumor cells, AP-1 is considered to be a driver whose activity is associated with dysfunction and the onset, development, invasion, and migration of cancer. In addition, AP-1 has been reported to be involved in the drug resistance and radiation resistance of tumor cells during the treatment process. Therefore, AP-1 is a potential target for cancer therapy. At present, a number of inhibitors targeting AP-1 have been developed and have shown certain anti-cancer effects. However, due to the complex structure and function of AP-1, different structures of AP-1 show different effects in different tumor cells, and more studies are needed to reveal its mechanism of action. This article introduces the relationship between AP-1 and tumor development, summarize the current studies and developments of AP-1 related drugs, and provide the future development values of AP-1.

Under the "Four Certificates in One" training model, the clinical medical professional postgraduate education of clinical medicine has increasingly revealed an imbalance between training and research development, highlighting a significant deficiency in cultivating students' scientific research capabilities.Currently, a well-structured educational framework to effectively nurture the research skills of clinical medical professional postgraduates remains lacking.This study focuses on clinical medical professional postgraduate students specializing in general surgery as the primary subjects of observation.By analyzing the current status of scientific research education for clinical medical professional postgraduate and drawing upon our institution’s recent teaching reform efforts, we explore specific strategies for developing research skills in clinical medical professional postgraduate students, particularly through a clinical problem-oriented approach.Furthermore, we offer reflections on the future direction of research education for clinical medical professional postgraduate, with the goal of fostering the development of well-rounded, high-quality medical professionals.

Abstract Lipid nanoparticles (LNPs) for mRNA delivery have advanced significantly, but LNP-mediated DNA delivery still faces clinical challenges. This study compared various LNP formulations for delivering DNA-encoded biologics, assessing their expression efficacy and the protective immunity generated by LNP-encapsulated DNA in different models. The LNP formulation used in Moderna’s Spikevax mRNA vaccine (LNP-M) demonstrated a stable nanoparticle structure, high expression efficiency, and low toxicity. Notably, a DNA vaccine encoding the spike protein, delivered via LNP-M, induced stronger antigen-specific antibody and T cell immune responses compared to electroporation. Single-cell RNA sequencing (scRNA-seq) analysis revealed that the LNP-M/pSpike vaccine enhanced CD80 activation signaling in CD8+ T cells, NK cells, macrophages, and DCs, while reducing the immunosuppressive signals. The enrichment of TCR and BCR by LNP-M/pSpike suggested an increase in immune response specificity and diversity. Additionally, LNP-M effectively delivered DNA-encoded antigens, such as mouse PD-L1 and p53R172H, or monoclonal antibodies targeting mouse PD1 and human p53R282W. This approach inhibited tumor growth or metastasis in several mouse models. The long-term anti-tumor effects of LNP-M-delivered anti-p53R282W antibody relied on memory CD8+ T cell responses and enhanced MHC-I signaling from APCs to CD8+ T cells. These results highlight LNP-M as a promising and effective platform for delivering DNA-based vaccines and cancer immunotherapies.

Abstract Organoid technology provides a transformative approach to understand human physiology and pathology, offering valuable insights for scientific research and therapeutic development. Human gastric organoids, in particular, have gained significant interest for applications in disease modeling, drug discovery, and studies of tissue regeneration and homeostasis. However, the lack of standardized quality control has limited their extensive clinical applications. The “Human Gastric Organoids” is part of a series of guidelines for human gastric organoids in China, which establishes comprehensive standards on terminology, technical specifications, testing methods, inspection rules, usage instructions, labeling, transportation, and storage, developed by experts from the Chinese Society for Cell Biology and its branch societies. Released on October 29, 2024, this guideline aims to establish standardized protocols, enhance institutional practices, and promote international standardization for clinical and research applications of human gastric organoids.

Abstract Background Sepsis is a systemic inflammatory syndrome that can cause coagulation abnormalities, leading to damage in multiple organs. Vascular endothelial cells (VECs) are crucial in the development of sepsis-induced coagulopathy (SIC). The role of Parthenolide (PTL) in regulating SIC by protecting VECs remains unclear. Methods The study utilized septic rats and lipopolysaccharide (LPS)-stimulated VECs to simulate a SIC model and observe the therapeutic effects of PTL. Additionally, nanotechnology was employed to produce Nano-PTL (N-PTL), to observe whether it has advantages over PTL in treating SIC. Results PTL has been shown to mitigate lung injury in septic rats, significantly reduce tumor necrosis factor-α (TNF-α) levels, and increase survival rates. PTL treatment also enhances coagulation function, augments vascular endothelial cell (VEC) function, reduces mitochondrial fragmentation, and increases both mitochondrial oxygen consumption rate (OCR) and mitochondrial membrane potential (MMP), while inhibiting reactive oxygen species (ROS) production. By increasing BRD4/BCL-xL levels, PTL can prevent mitochondrial-mediated apoptosis in VECs, improve VEC function, and consequently ameliorate SIC. Additionally, nanotechnology-synthesized N-PTL further enhances the protective effects on VECs and coagulation function. Conclusions This study clarifies the therapeutic effects and mechanisms of PTL on SIC, offering new strategies and directions for the treatment of sepsis.

Abstract The necessity of routinely placing closed suction wound drainage in spinal surgery has been questioned. This study aims to assess if closed suction wound drainage is necessary for posterior atlantoaxial fixation via intermuscular approach. The functional outcomes of these 40 patients who underwent posterior atlantoaxial fixation via intermuscular approach without drainage tube (Group A) were compared with that of a control group, which consisted of 68 randomly enrolled cases with posterior atlantoaxial fixation via intermuscular approach with drainage tube (Group B). Outcome assessments included American Spinal Injury Association (ASIA) scoring grade and Visual Analog Scale Score for Neck Pain (VASSNP). The postoperative analgesic consumption, the incidence of subcutaneous and surrounding ecchymosis and the time of ambulation were compared between two groups. Bone fusion was evaluated through computed tomography (CT) reconstruction. Postoperative paravertebral tissue edema was evaluated by the edema coefficient. The use of drainage tube had no significant influence on the postoperative analgesic consumption, wound ecchymosis, the time of ambulation and paravertebral tissue edema (P > 0.05). There were no statistically significant differences in the VASSNP and bone fusion rates during the follow-up period between the two groups (P > 0.05). All patients achieved ASIA grade E 3 months after surgery. No complications such as wound infection occurred in either group. Posterior atlantoaxial fixation via intermuscular approach does not necessitate postoperative drainage tube placement if there is no accidental vascular injury or excessive muscle bleeding occurs intraoperatively.

Abstract Ideal root system architecture (RSA) is important for efficient nutrient uptake and high yield in crops. We cloned and characterized a key RSA regulatory gene, GRAVITROPISM LOSS 1 (OsGLS1), in rice (Oryza sativa L.). The gls1 mutant displays an increased root growth angle, longer primary roots, more adventitious roots and greater nutrient uptake efficiency and grain yield in paddy fields. OsGLS1 is strongly expressed in the root tips of seedlings and in leaves at the flowering stage. OsGLS1 encodes a RING finger E3 ubiquitin ligase mainly localizing at the basal plasma membrane (PM) in several root cell types when phosphorylated on its Ser-30 residue. OsGLS1 interacts with, ubiquitinates and promotes the degradation of basally localized PIN-FORMED 2 (OsPIN2) via the 26S proteasome, thus establishing the typical apical PM localization of OsPIN2 and polar auxin transport, ultimately shaping RSA. This previously unidentified OsGLS1-OsPIN2 regulatory pathway will contribute to an optimal RSA for enhancing nutrient efficiency in rice and other crops.

AIM: To establish a stable, short-time, low-cost and reliable murine model of meibomian gland dysfunction (MGD). METHODS: A filter paper sheet soaked in 1.0 mol/L sodium hydroxide (NaOH) solution was used to touch the eyelid margin of C57BL/6J mice for 10s to establish the model. The other eye was left untreated as a control group. Eyelid margin morphological changes and the meibomian glands (MGs) were observed by slit lamp microscopy on days 5 and 10 post-burn. Hematoxylin-eosin (HE) staining and Oil red O staining were adopted in detecting the changes in MGs morphology and lipid deposition. Real-time polymerase chain reaction, Western blot, immunofluorescence staining and immunohistochemical staining were used to detect interleukin (IL)-6, IL-1β, IL-18, tumor necroses factor (TNF)-α, interferon (IFN)-γ, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4), 3-nitroturosine (3-NT), 4-hydroxynonenal (4-HNE) and cytokeratin 10 (K10) expression changes in MGs. RESULTS: MGs showed plugging of orifice, glandular deficiency, abnormal acinar morphology, ductal dilatation, and lipid deposition after alkali burn. The expressions of IL-6, IL-18, IL-1β, IFN-γ, and TNF-α indicators of inflammation and oxidative stress in MGs tissues were significantly increased. Abnormal keratinization increased in the MG duct. CONCLUSION: A murine model of MGD is established by alkali burn of the eyelid margin that matches the clinical presentation of MGD providing a stable, short-time, low-cost, and reliable MGD model. The new method suggests efficient avenues for future research.

This paper presents an analysis of four aspects, including the distribution and production of global oil and gas fields, the distribution and changes of remaining recoverable reserves, the differences in oil and gas production between regions/countries, and the development potentials of oil and gas fields unproduced and to be produced in 2023. On this basis, the situation and characteristics of global oil and gas development are expounded, and the trend of global oil and gas development is summarized. In 2023, upstream oil and gas production landscape is expanding, and the number of oil and gas fields in production is increasing significantly; oil and gas recoverable reserves increased year-on-year, driven by significant contributions from new discoveries and reserve re-estimates; the overall oil and gas production grew continuously, with notable contributions from new projects coming online and capacity expansion efforts; and the oil and gas fields unproduced or to be produced, especially large onshore conventional oil fields and economically challenging offshore gas fields, host abundant recoverable reserves. From the perspectives of reshaping oil and gas production areas due to the pandemic and Russia-Ukraine conflicts, geopolitical crises, capital expenditure structures in petroleum exploration and development, and the proactive layout of oil and gas associated resources, the trend of global oil and gas development in 2023 was analyzed systematically. The enlightenment and suggestions in four aspects are proposed for Chinese oil companies to focus on core businesses and clarify development strategies in the post-pandemic era and the context of energy transition: The global oil and gas landscape is undergoing profound adjustments, and it is essential to grasp development trends, especially in core businesses; upstream business exhibits a strong potential, and emerging fields are considered as new growth poles; the prospects for tight/shale oil and gas are promising, and new pathways to ensure national energy security are explored; cutting-edge breakthroughs are achieved in emerging industries of strategic importance, and a comprehensive energy collaboration system for supply security is established.

Lead-bismuth coolant in nuclear reactors generates and accumulates 210Po during operation, which has strong toxicity and high volatility. When the coolant leaks or the reactor is opened, some of the 210Po on the surface of the coolant and in the covering gas will diffuse out of the main system if not properly handled and released into the environment, posing a potential serious threat to the ecological environment and human health. The high-temperature distillation capture technology can effectively extract large amounts of 210Po from the lead-bismuth coolant. Since 210Po is an extremely toxic radioactive isotope with no stable isotope, and to facilitate the experimental study of the capture process, this study ultimately chose its isotopic cousin, Te, as a substitute for 210Po for experimental research. Measuring the trace amount of Te in the distillation capture product can provide strong support for the 210Po extraction process. In the experiment, Te was extracted from the distillation capture film using nitric acid, and the 717 strong basic anion resin was used to separate Te from the extraction solution to eliminate the interference of impurity ions. SnCl2 reduced Te4+ to Te in HCl medium, and the absorbance was measured on a spectrophotometer to obtain the content of trace Te in the sample. The influence of interfering ions in the extraction solution on the measurement value of Te was investigated; the effects of the pH of the column liquid, the concentration and amount of the elution agent, and the washing rate on the separation of Te were explored; and a spectrophotometric method for the determination of trace Te in the distillation capture product of lead-bismuth coolant was established. The results show that at room temperature, the HCl concentration of the column liquid is 4 mol/L, the eluent is ultrapure water, the washing rate is 2 mL/min. The 717 strong basic anion resin demonstrates excellent separation performance for Te across a concentration range of 0 to 10 mg/L, where the absorbance shows a strong linear correlation with Te concentration. The correlation coefficient is r2=0.999 9, with a relative standard deviation of measurement ranging from 0.3% to 2.7%(n=6). The recovery rate is between 96.0% and 101.9%. This measurement method satisfies the requirements for researching the 210Po extraction process.

Abstract Objective To analyze the pattern of lymph node metastasis in esophageal cancer based on the theory of membrane anatomy. Methods A retrospective analysis was conducted on 143 patients who underwent esophageal surgery at the Cancer Hospital of the Chinese Academy of Medical Sciences from March 2021 to March 2022. Lymph node metastasis was observed and categorized according to postoperative T staging. The characteristics and patterns of lymph node metastasis in different regions were observed, and the lymph node metastasis patterns in patients with clinical T3 esophageal cancer were analyzed using membrane anatomy theory. Results Among the 143 patients with esophageal squamous cell carcinoma, 21 were treated with surgery alone, while the rest received preoperative adjuvant therapy. A total of 5456 lymph nodes were cleared from the 143 patients, with 204 positive lymph nodes, resulting in a positive rate of 3.74%. In the thoracic lymph node dissection, the metastatic rates exceeded 5% for the following regions: 106recR (17.36%), 106recL (12.5%), 107 (10.42%), and 108 (5.56%) station. When analyzing the abdominal lymph node metastasis, the metastatic rates exceeded 5% for regions 7 (13.19%), 3a (7.64%), 2 (6.94%), and 1 (6.25%) station. Group analysis of patients with esophageal squamous cell carcinoma before postoperative pathological T3 stage revealed an increasing trend in tumor lymph node metastasis rate with later T staging. Lymph node metastasis in region 106recR can occur early, with a metastasis rate of 18.37% in T1 tumors. Analysis of lymph node metastasis characteristics in 103 patients clinically staged as T3 showed that 3966 lymph nodes were cleared, with 186 positive nodes, resulting in a positive rate of 4.69%. Lymph node metastasis rates were higher in regions 106recL, 106recR, 107, 108, 110, 1, 2, 3a, and 7, all exceeding 5%. Conclusion The theory of membrane anatomy can effectively explain the pattern of lymph node metastasis in esophageal cancer.

Abstract Background This study aimed to develop predictive models with robust generalization capabilities for assessing the risk of pulmonary embolism in patients with tuberculosis using machine learning algorithms. Methods Data were collected from two centers and categorized into development and validation cohorts. Using the development cohort, candidate variables were selected via the Recursive Feature Elimination (RFE) method. Five machine learning algorithms, logistic regression (LR), random forest (RF), extreme gradient boosting (XGBoost), light gradient boosting machine (LightGBM), and support vector machine (SVM), were utilized to construct the predictive models. Model performance was evaluated through nested cross-validation and area under the curve (AUC) metrics, supplemented by interpretations using Shapley Additive explanations (SHAP) and line charts of AUC values. Models were subjected to external validation using an independent validation group, facilitating the early identification and management of pulmonary embolism risks in tuberculosis patients. Results Data from 694 patients were used for model development, and 236 patients from the validation group met the enrollment criteria. The optimal subset of variables identified included D-dimer, smoking status, dyspnea, age, sex, diabetes, platelet count, cough, fibrinogen, hemoglobin, hemoptysis, hypertension, chronic obstructive pulmonary disease (COPD), and chest pain. The RF model outperformed others, achieving an AUC of 0.839 (95% CI 0.780–0.899) and maintaining the highest average performance in external fivefold cross-validation (AUC: 0.906 ± 0.041). Conclusions The RF model demonstrates high and consistent effectiveness in predicting pulmonary embolism risk in tuberculosis patients.

Abstract Gastric cancer is one of the most common malignancies with poor prognosis. The use of organoids to simulate gastric cancer has rapidly developed over the past several years. Patient-derived gastric cancer organoids serve as in vitro models that closely mimics donor characteristics, offering new opportunities for both basic and applied research. The “Human Gastric Cancer Organoid” is part of a series of guidelines for human gastric cancer organoids in China, jointly drafted by experts from the Chinese Society for Cell Biology and its branches, and initially released on October 29, 2024. This standard outlines terminology, technical requirements, assessment protocols, and applies to production, evaluation procedures, and quality control for human gastric cancer organoids. The publication of this guideline aims to assist institutions in endorsing, establishing, and applying best practices, advancing the international standardization of human gastric cancer organoids for clinical development and therapeutic application.

With the rapid development of nuclear science and technology，medical radioisotopes play an increasingly important role in nuclear medicine，and are widely used in the diagnosis and treatment of cardiovascular and cerebrovascular diseases，tumors and other diseases. Accelerator production of medical radioisotopes has the advantages of flexibility，efficiency，system safety and high nuclide activity，and is one of the important production methods to ensure the safe and stable supply of medical radioisotopes. In 2021，China Atomic Energy Authority together with seven other ministries，jointly released the “Medium - and Long Term Development Plan for Medical Isotopes (2021−2035)”，which clarifies that there are 14 important medical isotopes that China needs to focus on developing before 2035，of which 9 isotopes can be produced by accelerators. This article mainly introduces the production and application overview of accelerators for the 9 important medical isotopes listed in the plan. The 9 important medical isotopes include the imaging nuclides 123I，124I，64Cu，68Ga，89Zr and the therapeutic nuclides 186Re，103Pd，225Ac ,223Ra .Among them,225Ac、68Ge and 223Ra are the focus of isotope production in medium and high energy accelerators，and also are the main development trend of accelerator production radioisotopes. This study provides a comprehensive review of the nuclear properties，applications，reaction cross-sections，yields，and production methods of the diagnostic and therapeutic nuclides mentioned above，providing reference for the production of related nuclides.

68Ge is the parent nuclide of radioactive nuclide 68Ga used in positron emission tomography (PET) diagnostic imaging，which is converted into 68Ga by a 68Ge/68Ga generator for clinical diagnostic imaging applications. Currently，there are 13 kinds of 68Ga labeled radiopharmaceuticals in China that have entered clinical practice and have good application prospects in tumor imaging such as high-grade endocrine tumors and prostate cancer. Therefore，with the approval and widespread use of 68Ga radiopharmaceuticals，68Ge has broad application prospects in both domestic and international markets.In addition,68Ge can also be widely used as a calibration source for PET scanners.China Institute of Atomic Energy (CIAE) plans to build a 75 MeV cyclotron with the maximum beam current of 800 μA and the proton energy range of 75 MeV. It will be used to focus on the production of 68Ge nuclide.This article used the Monte Carlo program FLUKA to simulate in detail the production of 68Ge nuclides yield，reaction products，the variation of impurity nuclide production with cooling time，and long-life nuclides affecting separation processes by irradiating gallium nickel alloy targets and niobium gallium capsule targets in medium to high energy proton cyclotron.The simulation results can provide the useful reference for the production，separation，and purification of 68Ge in medium to high energy cyclotron.

This study focuses on the simulation of target preparation，dissolution，and separation- purification processes for the production of the vital medical radioactive isotope 68Ge using medium-high energy cyclotrons. It encompasses the preparation and quality inspection of gallium-nickel alloy targets，target dissolution，the establishment of analytical detection methods，and the optimization of simulation conditions for the separation and purification of 68Ge. Initially，gallium-nickel alloy targets were prepared on copper backing plates by optimizing the electrodeposition process conditions. Analytical detection methods were then established using inductively coupled plasma mass spectrometry (ICP-MS). Subsequently，the dissolution process of the gallium-nickel alloy targets was studied using an electrochemical anodic oxidation method. Finally，the combined use of Tulsimer CH-90 chelating resin and Sephadex G25 gel resin was employed to optimize the simulation conditions for the separation and purification of 68Ge，completing the process simulation study. The results indicate that the prepared gallium-nickel alloy targets have a smooth and flat surface with a uniform composition distribution，containing 74.7% gallium and 25.3% nickel，and have a thickness of 179 mg/cm2，suitable for medium-high energy proton irradiation above 30 MeV. The established ICP-MS internal standard method enables accurate quantitative detection of germanium and impurity elements. The electrochemical method allows for simple and rapid dissolution of the gallium-nickel alloy layer without heating. The combined use of chelating resin and gel resin for separation and purification yields germanium-containing sample solutions with high recovery rates and purity. Through the aforementioned process simulation studies，a simulated process flow for target preparation，target dissolution，analytical detection，and separation-purification has been established，providing technical support for the production of 68Ge using medium-high energy cyclotrons.

Abstract. Background:. The burden of esophageal cancer varies across different regions of the world. The aim of this study is to analyze the current burden of esophageal cancer in 185 countries in 2022 and to project the trends up to the year 2050. Methods:. We extracted data on primary esophageal cancer cases and deaths from the GLOBOCAN 2022 database, which includes data from 185 countries. Age-standardized incidence rates (ASIR) and mortality rates (ASMR) per 100,000 person-years were calculated by stratifying by Human Development Index (HDI) levels and regions. Considering changes in population size and age structure, we assumed that the risks of incidence and mortality remain constant at the levels of 2022 to forecast the number of new cases and deaths from esophageal cancer globally by 2050. Results:. In 2022, an estimated 511,054 people were diagnosed with esophageal cancer globally, and 445,391 died from the disease. The global ASIR and ASMR for esophageal cancer were 5.00 and 4.30 per 100,000, respectively. The highest rates were observed in East Africa (7.60 for incidence, 7.20 for mortality per 100,000), East Asia (7.60 for incidence, 5.90 for mortality per 100,000), Southern Africa (6.30 for incidence, 5.90 for mortality per 100,000), and South Central Asia (5.80 for incidence, 5.50 for mortality per 100,000). Among the 185 countries worldwide, esophageal cancer was among the top five causes of cancer incidence in 18 countries and among the top five causes of cancer mortality in 25 countries. In 2022, China had 224,012 new cases and 187,467 deaths from esophageal cancer, accounting for approximately 43.8% and 42.1% of the global total, respectively, which is higher than the proportion of China’s population to the global population (17.9%). ASIR was 8.30 per 100,000, and ASMR was 6.70 per 100,000. The highest burden of esophageal cancer was in high HDI countries, with new cases and deaths accounting for 51.3% and 50.0% of the global total, respectively. The ASIR and ASMR were highest in the high HDI group (6.10 and 5.10 per 100,000, respectively), also exceeding the global averages. There was a trend of decreasing mortality to incidence ratio with increasing HDI, but no correlation was observed between HDI and ASIR or ASMR. In all regions worldwide, the incidence and mortality rates were higher in males than in females (with a male-to-female ASR ratio ranging from 1.10 to 28.7). Compared to 2022, it is projected that by 2050, the number of new esophageal cancer cases will increase by approximately 80.5%, and deaths will increase by 85.4% due to population growth and aging. Conclusions:. The burden of esophageal cancer remains heavy. Adopting a healthy lifestyle, including reducing tobacco and alcohol intake, avoiding moldy foods, and increasing intake of fresh fruits and vegetables, can help reduce the risk of stomach and esophageal cancer. In addition, the development and implementation of evidence-based and effective public health policies are critical to reducing the global disease burden of esophageal cancer.

In recent years, with the continuous scale expansion of surface coal mining in China, the stability and safety of slopes in surface mining areas have received more and more attention. The slopes of the Baozhixil surface coal mine located in the Chenqi coal field are characterised by low rock strength, small inclination of strata and weak interlayers, which are prone to serious sliding damage under rainfall conditions. In order to investigate the damage mechanism of such slopes under rainfall conditions and the control effect of the NPR anchor cable support system on such slopes, model experiments and numerical simulations were used. The results show that: ① from the field damage characteristics and model test results, it can be seen that the slope damage mode is the slope shear-slip caused by weak layer belt damage under the action of rainfall. The rainfall infiltration is the main factor inducing the destruction of the slope. The damage is divided into three phases: the initial deformation, the destruction of weak layer and the overall destruction. From the results of displacement monitoring, it can be seen that the slope cracks can be up to 35 mm wide, indicating that the slope slippage damage. ② From the numerical simulation analysis, it can be seen that the slope deformation increases significantly under rainfall conditions, and the maximum deformation can be up to 40 cm without anchoring measures. At the same time, the closer to the coal seam position, the larger the area of the plastic zone of slope shear damage, and the landslide body appears to have a large area of shear damage after sliding along the weak layer of the rock body, which verifies the deformation form of slope shear-slip damage. ③ From the comparative analysis of the NPR anchor cable reinforcement scheme and the PR anchor cable reinforcement scheme, it can be seen that the supporting effect of the NPR anchor cable is much better than that of the PR anchor cable, the maximum displacement of the slope under the NPR anchor cable support is reduced by 17.6 cm, while the maximum displacement of the slope under the PR anchor cable support is reduced by only 10.3 cm. The plastic damage zone under the NPR anchor reinforcement basically disappears, while the plastic damage zone under the PR anchor reinforcement still exists and extends to the depth of the slope, and the slope has the potential of landslide. The study investigated the damage mechanism of the near-level weak layer slope under rainfall conditions, proposed the NPR anchor reinforcement scheme and verified its feasibility, which provides a certain reference basis for related slope projects.

Abstract In this paper, we investigate the decoding performance and corresponding decoding strategies for polar-coded orthogonal frequency division multiplexing (OFDM) system operating under multipath fading channels. Multipath fading channels lead to frequency selective fading of the OFDM signal, resulting in varying levels of noise interference across different subcarriers after equalization. Furthermore, frequency selective fading induces burst errors in the equalized information, thereby significantly degrading the decoding performance. To address these issues, we propose two schemes in this paper to enhance the decoding performance of polar-coded OFDM system. Firstly, we integrate the channel state information of each subcarrier into the generation of soft information for the polar codes decoder, in order to alleviate the degradation of decoding performance caused by variations in signal-to-noise ratio across subcarriers during OFDM demodulation. Secondly, we introduce a packet interleaving design after the polar codes encoder to enhance the robustness of polar codes against burst errors. Simulation results demonstrate that the combined application of these two decoding strategies significantly outperforms the conventional scheme in terms of transmission performance over multipath fading channels. The findings of this study suggest that, within the context of future wireless communication systems utilizing Polar-OFDM, the concurrent implementation of our two proposed decoding strategies is essential for achieving robust error correction performance in the OFDM system.

Abstract The dynamic regulation of chromatin accessibility is one of the prominent characteristics of eukaryotic genome. The inaccessible regions are mainly located in heterochromatin, which is multilevel compressed and access restricted. The remaining accessible loci are generally located in the euchromatin, which have less nucleosome occupancy and higher regulatory activity. The opening of chromatin is the most important prerequisite for DNA transcription, replication, and damage repair, which is regulated by genetic, epigenetic, environmental, and other factors, playing a vital role in multiple biological progresses. Currently, based on the susceptibility difference of occupied or free DNA to enzymatic cleavage, solubility, methylation, and transposition, there are many methods to detect chromatin accessibility both in bulk and single-cell level. Through combining with high-throughput sequencing, the genome-wide chromatin accessibility landscape of many tissues and cells types also have been constructed. The chromatin accessibility feature is distinct in different tissues and biological states. Research on the regulation network of chromatin accessibility is crucial for uncovering the secret of various biological processes. In this review, we comprehensively introduced the major functions and mechanisms of chromatin accessibility variation in different physiological and pathological processes, meanwhile, the targeted therapies based on chromatin dynamics regulation are also summarized.

AIM: To assess the corneal high-order aberration (HOA) and its correlation with corneal morphological parameters in patients with bilateral keratoconus (KCN) and unilateral Vogt's striae. METHODS: A total of 168 eyes of 84 patients with KCN, whose corneas had definite signs of unilateral Vogt's striae, were enrolled. Corneal HOA and morphological parameters were measured using Pentacam HR. RESULTS: The corneal morphological parameters between KCN eyes with and without Vogt's striae were evidently different (P

Immune checkpoint blockade (ICB) therapy is a widely favored anti-tumor treatment, but it shows limited response to non-immunogenic “cold” tumors and suffers from drug resistance. Photodynamic therapy (PDT), as a powerful localized treatment approach, can convert a “cold tumor” into a “hot tumor” by inducing immunogenic cell death (ICD) in tumor cells, thereby enhancing tumor immunogenicity and promoting tumor immunotherapy. However, the effectiveness of PDT is largely hindered by the limited penetration depth into tumor tissues. To address these issues, we proposed an all-in-one drug system with NIR-II photo-accelerated PDT effects, efficient immune checkpoint gene silencing, and a facile manufacturing process. The so-called all-in-one drug system comprises a multi-modal designed polymer PPNP and siRNA. PPNP is an amphipathic polymer that includes the near infrared-II (NIR-II) photosensitizer Aza-boron-dipyrromethene (Aza-BODIPY), a glutathione (GSH)-cleavable linker, and a cationic monomer derived from cholesterol. PPNP can self-assemble and efficiently load siRNA. Under laser irradiation, PPNP triggers a potent ICD cascade, causing the on-demand release of siPD-L1, reshaping the tumor's immunosuppressive microenvironment, effectively inhibiting the growth of various tumors, and stimulating the immune memory. This study represents a generalized platform for PDT and gene silencing, designed to modulate immune-related signaling pathways for improved anticancer therapy.

The development of ultra-high strength steels with balanced ductility and toughness is of significant industrial importance. In the present study, impact toughness, tensile properties, and microstructural evolution of high-Co-Ni secondary hardening steels were investigated by adding Ni from 13 to 15 wt%. Within a certain range, Ni effectively refines the grain size and the thickness of austenite films, facilitating the enrichment of Ni in nanoscale film reverted austenite, thereby enhancing the austenite stability and toughness in steels.At a Ni concentration of 14 wt%, the steel exhibits the most refined martensitic substructure and nanoscale film-like reverted austenite, enriched with Ni, along with the precipitation of a significant volume of nanoscale semi-coherent (Mo,Cr)2C phases. This microstructural configuration yields an optimal synergy of strength and toughness, with an ultimate tensile strength reaching approximately 2.3 GPa and a Charpy impact energy of around 34 J. However, an increment in Ni content results in a higher volume fraction of Ni-enriched reverted austenite, which poses challenges to eliminate during low-temperature and aging processes, consequently reducing the steel's toughness. This comprehensive study provides a foundation for the design of ultra-high-strength alloys with tailored strength and toughness, highlighting the pivotal role of Ni in achieving this balance.

The hot deformation and fracture behavior of TC4 with and without diffusion bonding (DB) are investigated in both experimental and numerical methods in this study. The hot tensile tests of TC4 specimens with and without DB have been carried out at a temperature of 750 °C and strain rate of 0.1–0.0001 s−1, and the corresponding microstructure and fracture morphology under different deformation conditions have been analyzed by scanning electron microscope (SEM) and electron back scatter diffraction (EBSD). Straight grain boundaries, fine dynamic recrystallization (DRX) grains and weak joints formed by the DB process, which lead to lower stress and fracture strain than those of base metal (BM) specimens. Based on the experimental results, a new unified constitutive model considering the weld-dependent fracture coefficients and internal variables is developed, which can accurately predict the hot deformation and fracture behavior of TC4 with and without DB, describing the influence behavior of DB interface on hot deformation, as well as the evolutions of internal variables, including dislocation density, reserve fraction, DRX fraction and damage. The constitutive model has been further applied to the finite element method (FEM), and the prediction ability of the deformation behavior and the fracture of the model for hot deformation processes have been verified. It provides a theoretical basis for further accurate simulation of the hot forming of titanium alloy with DB.

Abstract Background Pulse oximeters are vital for assessing blood oxygen levels but can produce inaccurate readings during patient motion, leading to false alarms and alarm fatigue. Analog SpO2 Technology, which uses analog waveforms to filter motion artifacts, may improve accuracy compared to digital sensors. However, the effectiveness of this technology in reducing false alarms in clinical settings remains unclear. This study assesses and compares the motion resistance of Analog SpO2 Technology of two devices in the market. Methods Thirty healthy adults underwent controlled experiments (Control, Linear Motion, Angular Motion) using two pulse oximeters. Linear Motion tested hand displacement impact, while Angular Motion involved rhythmic hand motions at 120 bpm and 160 bpm. Results Both devices performed similarly in Control, with no disruptions. In Linear Motion, mild disruptions occurred, but no significant differences in SpO2 readings or alarms. Angular Motion at 120 bpm showed stability with no alarms. At 160 bpm, Device B (Biolight Analog SpO2) had fewer technical alarms but more SpO2 alarms than Device A (Masimo Analog SpO2). Conclusions Analog SpO2 exhibited motion resistance under static, linear and continuous waving angular motion up to 120 bpm and 160 bpm, but alarms occurred at 160 bpm with continuous tapping angular motion. These findings signify non-inferiority of either device in clinical settings. Further studies should include patients with cardiovascular and/or respiratory diseases. Trial Registration The study was submitted to and approved by the Biolight Ethics Committee (S0723), and written informed consent from all participants was obtained.

This study explores the influence of cryogenic supersonic fine particle bombardment (CSFPB) on a Ni–W–Co–Ta medium heavy alloy (MHA), and focus on the effect of gas pressure and impact time on the surface integrity, microstructural evolution, and mechanical properties of the MHA. CSFPB treatment creates a gradient structure, including surface layer with nanograins down to 9.0 nm due to severe plastic deformation, subsurface layer with high density dislocation structures and deformation twins due to weakened impact energy, and undeformed matrix. A key advantage of CSFPB is seen to be the cryogenic environment, which promotes superior surface integrity by reduced roughness. As the impact duration and gas pressure increase, the depth of deformation layer, surface hardness and strength of the MHA progressively rise. The optimal combination of strength and ductility is achieved at a gas pressure of 1.0 MPa for a duration of 90 s. This setting results in a maximum ultimate tensile strength of 1351 MPa and yield strength 796 MPa, with uncompromising elongation. However, excessively long treatment durations or high gas pressures can lead to the formation of surface microcracks, ultimately reducing the MHA's strength. Therefore, CSFPB offers the benefit of improved surface integrity through the cryogenic environment while maintaining a desirable balance between enhanced strength and ductility.

Abstract To address the conservative excavator working device configuration obtained by traditional design methods, a lightweight structure design method was proposed in this study based on automatically generated surrogate model. A finite element model of the working device was first constructed, and its accuracy was verified against experimental results. By incorporating the Gini coefficient to compute the information entropy pertaining to the relationship between variables and responses, the entropy-weighted TOPSIS method has been significantly enhanced. Subsequently, the comprehensive contributions of the boom design parameters to the mass, deformation, and stress responses were calculated, and the parameters exerting significant effects were selected as the design variables through the application of the improved TOPSIS. Next, the working device optimisation model was subsequently established using the minimum mass as the target and the stress and deformation as constraints. And then, a surrogate model of the working device was constructed using 500 sample points. Finally, a genetic algorithm was employed to derive a lightweight design of the excavator boom based on the surrogate model. The results indicate that the proposed method reduced the weight of the considered hydraulic excavator boom by 9.30%; further, a finite element simulation verified that the stress and deformation met the design requirements of the boom.

Abstract The numerous grainboundaries solid electrolyte interface, whether naturally occurring or artificially designed, leads to non-uniform Li metal deposition and consequently results in poor full-battery performance. Herein, a lithium-ion selective transport layer is reported to achieve a highly efficient and dendrite-free lithium metal anode. The layer-by-layer assembled protonated carbon nitride nanosheets present uniform macroscopical structure without grainboundaries. The carbon nitride with ordered pores in basal plane provides high-speed lithium-ion transport channels with low tortuosity. Consequently, the assembled 324 Wh kg−1 pouch cell exhibits 300 stable cycles with a capacity retention of 90.0% and an average Coulombic efficiency up to 99.7%. The ultra-dense Li metal anode makes current collector-free anode possible, achieving high energy density and long cycle life of a 7 Ah cell (506 Wh kg−1, 160 cycles). Thus, it is proved that a macroscopically uniform interface layer with lithium-ion conductive channels could achieve Li metal battery with promising application potential.

Abstract Cuproptosis is an emerging mode of programmed cell death for tumor suppression but sometimes gets resisted by tumor cells resist under specific mechanisms. Inhibiting copper transporter ATPase (ATP7A) was found to disrupt copper ion homeostasis, thereby enhancing the effect of cuproptosis and eventually inhibiting tumor invasion and metastasis. In this study, we develop a multifunctional nanoplatfrom based on Cu9S8 (CAPSH), designed to enhance cuproptosis in tumor cells by specifically targeting ATP7A interference, while combining thermodynamic therapy with immune effects. The release of copper ions from CAPSH and the copper homeostasis interference by siRNA cooperatively increases the concentration of copper ions in tumor cells, which induces effectively cuproptosis and activates immune responses for suppressing development and metastasis of tumor. This nanoplatform simultaneously regulates cuproptosis from both principles of onset and development, facilitating the application of cuproptosis in tumor therapy.

The fluorescent advanced glycation end products (AGEs) and two typical AGEs, Nε-carboxymethyl-lysine (CML) and Nε-carboxyethyl-lysine (CEL) were identified in Pleurotus eryngii chips using fluorescence spectroscopy and ultra-performance liquid chromatography-triple quadrupole tandem mass spectrometry, respectively. Additionally, the effect of frying temperatures and times on the quality of Pleurotus eryngii chips was investigated. The results showed that the Pleurotus eryngii chips underwent browning during the frying process, with the color changing from white to golden yellow. The color intensified as the air-frying time and temperature increased. The crispy slices had a significantly (P

In this study, particle-reinforced aluminium matrix composites (PRAMCs) of an Al–Cu–Li alloy were prepared using nano-sized TiB₂+TiC particles. The relationship between TiB₂+TiC nanoparticles and T1 precipitates during the ageing process, as well as the influence of TiC + TiB₂ particles on the growth process of T1 precipitates during the ageing process, were investigated. The grain sizes of the A0 and A1 samples were found to be 249.89 μm and 86.42 μm, respectively. The dislocation density is greater in the deformed A1 sample. The coefficient of thermal expansion (CTE) effect generated by TiC and TiB₂ particles stimulates the precipitation process of T1 precipitates. The A1 alloy reached the peak ageing state in a shorter time and yielded a greater number of T1 precipitates. The precipitation process of T1 precipitate is: SSSS→T1P→T1. The transition from T1P (face-centered cubic, FCC) to T1 (hexagonal close packing, HCP) entails a modification in the order of packing. The recently formed T1P precipitate is attached to the established T1 precipitate and extends along the c-axis through the shared copper-rich layer that has formed on both sides of the mature T1 precipitate. The mechanical properties of sample A1 are optimal at T = 22h, with a yield strength, tensile strength, and elongation of 520 MPa, 553 MPa, and 8.2%, respectively. In comparison to the A0 sample, the yield strength and tensile strength exhibited an increase of 5.05% and 5.13%, respectively.

The effects of sintering temperatures on the microstructures and mechanical properties of titanium carbide particles reinforced iron matrix composites (TiC/Fe MCs) fabricated by the spark plasma sintering (SPS) process with pure element powders have been systematically investigated. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), electron back scattering diffractometer (EBSD), and energy dispersive spectroscopy (EDS) have been conducted for microstructural analysis. The results show that with increasing sintering temperatures, the porosity of the composites initially decreases and then increases. Simultaneously, the grain size gradually diminishes while element diffusion becomes more uniform. Upon reaching a critical sintering temperature (1120 °C), the original grain size disappears and carbides undergo decomposition and reprecipitation to reach an equilibrium state, with which optimal comprehensive properties can be achieved (porosity decreases to a minimum of 3.85%, grain size of 2.69 μm, Vickers hardness reaches 595 HV0.5, bending strength is at 662 MPa, coefficient of friction is at 0.74, and wear loss to 0.21 mg). These property enhancements have been attributed to reduced porosity in the composites, decreased grain size, and improved anchoring effect of carbides within the matrix. Additionally, the primary fracture mechanisms and wear mechanisms of TiC/Fe MCs with different process parameters have been analyzed. When the temperature is below 1080 °C, intergranular fracture predominates, whereas transgranular and ductile fractures become predominant above this threshold. When the temperature is below 1120 °C, fatigue wear, oxidation wear, and abrasive wear are predominantly observed. Conversely, when the temperature exceeds 1120 °C, oxidation wear and abrasive wear become the primary mechanisms.

In this work, the environmental fracture behavior of marine steel and its welding joint were compared in artificial seawater. The electrochemical measurement, slow strain rate tensile test, and low-frequency cyclic loading test were conducted. The results showed that the corrosion current density and stress corrosion cracking susceptibility of welding joints were higher than those of base metal, caused by high dislocation density and residual stress in the heat-affected zone. The acidification and ion concentration occurred at the crack tip of the welding joint and basic metal. pH value and Cl− concentration at the crack tip reached 4.1 and 3.8 mol/L, respectively. The crack growth rate of the welding joint was higher than that of base metal. The crack growth behavior was controlled by the mechano-electrochemical effect at the crack tip, and hydrogen embrittlement was the main factor.

Abstract A dc voltage restorer (dc‐VR) with optimal droop control is developed to reduce the power loss and solve the dynamic current imbalance simultaneously of the zonal dc distribution system integrating multi‐parallel energy storage. Firstly, the power loss model composed of line loss and converter loss is built and it is proved to be a strictly convex function with respect to droop coefficients, which indicates the power loss can be mitigated by optimizing the current distribution. Thus, an image‐based droop optimization method is proposed to search for the optimal droop coefficients. Then, the economy of voltage compensation on power loss reduction is investigated and an ESS‐combined dc‐VR is designed, including an interleaved parallel architecture and a capacitor‐integrated electric spring (C‐ES). Unified virtual inertia is proposed for interleaved parallel bridge arms to make their dynamic performance consistent. And the newly introduced C‐ES can keep the bus voltage at the rated level to reduce the system cost. Therefore, the problem of dynamic currents imbalance is addressed from the points of converter structure (dc‐VR) and control system (unified inertia), and the power loss can be reduced by voltage recovery (C‐ES) and optimizing the current reallocation which is achieved by updating sharing coefficients from the image‐based droop optimization method. Finally, the simulation cases validate the effectiveness of the proposed optimal‐droop dc‐VR on dynamic current balance and power loss reduction, and hardware in the loop experiment results prove the consistent dynamic characteristics of the dc‐VR's arms.

Abstract While social media platforms promote people’s information exchange and dissemination, they also make rumors spread rapidly on online platforms. Therefore, how to detect rumors quickly, timely and accurately has become a hot topic for scholars in related fields. Traditional deep learning models ignore the relationship and topology between nodes in the rumor detection task and use fixed weights or mean aggregation strategies in the feature aggregation process, which fail to capture the complex interactions between nodes and the dynamics of information propagation, limiting the accuracy and robustness of the rumor detection model. To address these problems, we propose a location-aware weighted GraphSAGE rumor detection model GSMA. We first introduce an attention mechanism that dynamically assigns different attention weights to different neighboring nodes for different degrees of aggregation, improving GraphSAGE’s strategy of using mean-value aggregation for all neighboring nodes during the aggregation process; second, we introduce a modulated position encoding into the model and encode the position information of nodes into the features to improve the model’s ability to perceive the relative position and order of nodes; finally, the post text sentiment is incorporated into the features to provide additional semantic information for the model as a way to achieve rumor detection in microblogging platforms. Experiments show that the accuracy of the GSMA model on Ma-Weibo and Weibo23 reaches 97.43% and 97.55%, which is an improvement of 1.11% and 0.77% compared to the benchmark GraphSAGE, and all the evaluation metrics are also improved compared to other optimal rumor detection models.

Abstract Long non-coding RNAs (lncRNAs) have a notable role in the diagnosis and prognosis of cancer. However, the associations between lncRNA-related hub genes (LRHGs) expression and the corresponding outcomes have not been fully understood in lung adenocarcinoma (LUAD). Here, a total of 71 patients diagnosed with LUAD and 60 healthy volunteers at The First Affiliated Hospital of Huzhou University from April, 2023 to December, 2023 were enrolled in the present study. A LRHGs model was established using least absolute shrinkage and selection operator analyses of The Cancer Genome Atlas-LUAD datasets. The underlying mechanisms of the LRHGs were investigated via Gene Set Enrichment Analysis and Gene Set Variation Analysis. Additionally, the diagnostic role of serum HOXD cluster antisense RNA 2 (HOXD-AS2) was assessed by receiver operating characteristic (ROC) curve analysis. Lastly, TCGA-LUAD samples were divided into high- and low-HOXD-AS2 expression groups based on the median expression. The associations between HOXD-AS2 expression and miR-4538 as well as Calmodulin-Dependent Protein Kinase Type II subunit Beta (CAMK2B) levels were conducted through Pearson correlation analysis. A comprehensive analysis identified 141 differentially expressed lncRNAs between 539 LUAD tissues and 59 normal samples. A prognostic marker for overall survival was established by constructing a predictive signature consisting of 9 LRHGs. Subsequently, 474 LUAD samples were categorized into a high or low-risk group based on the median of the risk score. An independent prognostic model was constructed to confirm the validity of this categorization. Further comparisons of the clinicopathological features and LRHG-related pathways were performed between the two groups. Examinations of LRHG expression in two LUAD clusters and of the association between LRHG expression and immune infiltration were also conducted. HOXD-AS2 expression was shown to be elevated in LUAD tissues compared with matched normal tissues, and the serum HOXD-AS2 level was also notably increased in LUAD samples compared with healthy controls. The results of the ROC analysis indicated that the sensitivity and specificity of HOXD-AS2 were higher than that of cytokeratin-19 fragment (CYFRA21-1), which is a serum marker for LUAD. Pearson analyses indicated that miR-4538 level was negatively associated with HOXD-AS2 expression, but CAMK2B level showed positive correlation in LUAD. The results of the present study therefore indicated that the constructed LRHG model, particularly HOXD-AS2, could independently diagnose and predict the prognosis of LUAD, which suggested the underlying mechanism of the HOXD-AS2/miR-4538/CAMK2B, and might offer efficient strategies for LUAD treatment.

Abstract Background Cuproptosis, a recently identified type of programmed cell death triggered by copper, has mechanisms in Wilms tumor (WT) that are not yet fully understood. This research focuses on examining the link between WT and Cuproptosis-related genes (CRGs), with the goal of developing a predictive model for WT. Methods Four gene expression datasets related to WT were sourced from the GEO database. Subsequently, expression profiles of CRGs were extracted for differential analysis and immune infiltration studies. Utilizing 105 WT samples, clusters related to Cuproptosis were identified. This involved analyzing associated immune cell infiltration and conducting functional enrichment analysis. Disease-characteristic genes were pinpointed using weighted gene co-expression network analysis. Finally, the WT risk prediction model was constructed by four machine learning methods: random forest, support vector machine (SVM), generalized linear and extreme gradient strength model. The best-performing machine learning model was chosen, and a nomogram was created. The effectiveness of this predictive model was validated using methods such as the calibration curve, decision curve analysis, and by appiying it to the TARGET-GTEx dataset. Results Thirteen differentially expressed Cuproptosis-related genes were identified. The infiltration level of CD8 + T cells in WT children was lower than that in Normal tissue (NT) children, and the level of M0 infiltration of macrophages and T follicular helper cells was higher than that in NT children. In addition, two clusters of cuproptosis-related WT were identified. Enrichment analysis results indicated that genes in cluster 2 were primarily involved in cell division, nuclear division regulation, DNA biosynthesis process, ubiquitin-mediated proteolysis. The SVM model was judged to be the optimal model using 5 genes. Its accuracy was confirmed through a calibration curve and decision curve analysis, demonstrating satisfactory performance on the TARGET-GTEx validation dataset. Additional analysis revealed that these five genes exhibited high expression in both the TARGET-GTEx validation dataset and sequencing data. Conclusion This research established a link between WT and Cuproptosis. It developed a predictive model for assessing the risk of WT and pinpointed five key genes associated with the disease.

Abstract Multiple myeloma (MM), a hematological malignancy of the bone marrow, remains largely incurable. The orphan G protein-coupled receptor, GPRC5D, which is uniquely expressed in plasma cells and highly expressed in MM, is a compelling candidate for immunotherapy. In this study, we investigated the efficacy of a combination of DNA vaccine encoding mouse GPRC5D and PD-1 blockade in preventing and treating MM using the 5TGM1 murine model of MM. The mouse vaccine alone was effective in preventing myeloma growth but required PD-1 antibodies to inhibit established MM tumors. We next evaluated the prophylactic and therapeutic efficacy of a nanoplasmid vector encoding human GPRC5D in several murine syngeneic tumor models. Similar results for tumor inhibition were observed, as human GPRC5D-specific T cells and antibodies were induced by DNA vaccines. Taken together, these findings underscore the potential of GPRC5D-targeted DNA vaccines as versatile platforms for the treatment and prevention of MM.

Abstract Air quality is closely linked to human health and social development, making accurate air quality prediction highly significant. The Air Quality Index (AQI) is inherently a time series. However, most previous studies have overlooked its temporal features and have not thoroughly explored the relationship between pollutant emissions and air quality. To address this issue, this study establishes a historical correlation model for air quality based on a time series model—the Gaussian Hidden Markov Model (GHMM)—using industrial exhaust emissions and historical air quality data. Firstly, a traversal method is used to select the optimal number of hidden states for the GHMM. To optimize the traditional GHMM and reduce error accumulation in the prediction process, the Multi-day Weighted Matching method and the Fixed Training Set Length method are utilized. Both direct and indirect prediction modes are then used to predict the AQI in the Zhangdian District. Experimental results indicate that the improved GHMM with the indirect mode provides higher accuracy and more stable state estimation results (MAE = 13.59, RMSE = 17.59, mean forecasted value = 117.94). Finally, the air quality historical correlation model is integrated with the air quality meteorological correlation model from a previous study, further improving prediction accuracy (MAE = 11.59, RMSE = 14.87, mean forecasted value = 120.88). This study demonstrates that the GHMM’s strong ability to analyze temporal features significantly enhances the accuracy and stability of air quality predictions. The integration of the air quality historical correlation model with the air quality meteorological correlation model from a previous study leverages the strengths of each sub-model in handling different feature groups, leading to even more accurate predictions.

Abstract Micro-expressions are spontaneous, rapid and subtle facial movements that can hardly be suppressed or fabricated. Micro-expression recognition (MER) is one of the most challenging topics in affective computing. It aims to recognize subtle facial movements which are quite difficult for humans to perceive in a fleeting period. Recently, many deep learning-based MER methods have been developed. However, how to effectively capture subtle temporal variations for robust MER still perplexes us. We propose a counterfactual discriminative micro-expression recognition (CoDER) method to effectively learn the slight temporal variations for video-based MER. To explicitly capture the causality from temporal dynamics hidden in the micro-expression (ME) sequence, we propose ME counterfactual reasoning by comparing the effects of the facts w.r.t. original ME sequences and the counterfactuals w.r.t. counterfactually-revised ME sequences, and then perform causality-aware prediction to encourage the model to learn those latent ME temporal cues. Extensive experiments on four widely-used ME databases demonstrate the effectiveness of CoDER, which results in comparable and superior MER performance compared with that of the state-of-the-art methods. The visualization results show that CoDER successfully perceives the meaningful temporal variations in sequential faces.

Abstract High altitude exposure negatively affects human attentional function. However, no studies have explored the regulation of attentional and physiological functions from a dietary perspective. A total of 116 Han Chinese students from Tibet University who were born and raised in a plain area and had been living in Tibet for > 2 years were recruited. All participants were male migrants. A food frequency questionnaire, complete blood count, and attention network test were performed on the participants. Pearson’s correlation was applied to assess the reliability and validity of the food frequency questionnaire. Principal component analysis was utilized to extract dietary patterns. A linear mixed model was employed to account for individual differences. The results showed that the five main dietary patterns were coarse grain, alcohol, meat, protein, and snacking dietary patterns. Furthermore, individuals who adhered to the coarse grain dietary pattern and had high mean corpuscular hemoglobin showed better attentional performance. Individuals with high alcohol consumption and systemic immune-inflammation index levels exhibited worse attentional performance. These findings imply that high-altitude migrants should include more coarse grains in their daily diet and avoid excessive alcohol consumption to improve attention.

Abstract PROTAC® (proteolysis-targeting chimera) molecules induce proximity between an E3 ligase and protein-of-interest (POI) to target the POI for ubiquitin-mediated degradation. Cooperative E3-PROTAC-POI complexes have potential to achieve neo-substrate selectivity beyond that established by POI binding to the ligand alone. Here, we extend the collection of ubiquitin ligases employable for cooperative ternary complex formation to include the C-degron E3 KLHDC2. Ligands were identified that engage the C-degron binding site in KLHDC2, subjected to structure-based improvement, and linked to JQ1 for BET-family neo-substrate recruitment. Consideration of the exit vector emanating from the ligand engaged in KLHDC2’s U-shaped degron-binding pocket enabled generation of SJ46421, which drives formation of a remarkably cooperative, paralog-selective ternary complex with BRD3BD2. Meanwhile, screening pro-drug variants enabled surmounting cell permeability limitations imposed by acidic moieties resembling the KLHDC2-binding C-degron. Selectivity for BRD3 compared to other BET-family members is further manifested in ubiquitylation in vitro, and prodrug version SJ46420-mediated degradation in cells. Selectivity is also achieved for the ubiquitin ligase, overcoming E3 auto-inhibition to engage KLHDC2, but not the related KLHDC1, KLHDC3, or KLHDC10 E3s. In sum, our study establishes neo-substrate-specific targeted protein degradation via KLHDC2, and provides a framework for developing selective PROTAC protein degraders employing C-degron E3 ligases.

Based on the oil and gas exploration in the Sichuan Basin, combined with data such as seismic, logging and geochemistry, the basic geological conditions, hydrocarbon types, hydrocarbon distribution characteristics, source- reservoir relationship and accumulation model of the Upper Triassic–Jurassic continental whole petroleum system in the basin are systematically analyzed. The continental whole petroleum system in the Sichuan Basin develops multiple sets of gas-bearing strata, forming a whole petroleum system centered on the Triassic Xujiahe Formation source rocks. The thick and high-quality source rocks in the Upper Triassic Xujiahe Formation provide sufficient gas source basis for the continental whole petroleum system in the basin. The development of conventional-unconventional reservoirs provides favorable space for hydrocarbon accumulation. The coupling of faults and sandbodies provides a high-quality transport system for gas migration. Source rocks and reservoirs are overlapped vertically, and there are obvious differences in sedimentary environment, reservoir lithology and physical properties, which lead to the orderly development of inner-source shale gas, near-source tight gas, and far-source tight–conventional gas in the Upper Triassic–Jurassic, from bottom to top. The orderly change of geological conditions such as burial depth, reservoir physical properties, formation pressure and hydrocarbon generation intensity in zones controlled the formation of the whole petroleum system consisting of structural gas reservoir in thrust zone, shale gas-tight gas reservoir in depression zone, tight gas reservoir in slope zone, and tight gas–conventional gas reservoir in uplift zone on the plane. Based on the theory and concept of the whole petroleum system, the continental shale gas and tight gas resources in the Sichuan Basin have great potential, especially in the central and western parts with abundant unconventional resources.

Abstract Maternal use of e-cigarette (e-cig) aerosols poses significant risks to fetal brain development, potentially increasing susceptibility to neurodevelopmental disorders in later life. However, the underlying mechanisms remain incompletely understood. This study aimed to understand the effects of fetal e-cig exposure on DNA methylome and transcriptomic changes in the neonatal brain. Pregnant rats were exposed to e-cig aerosols, and neonatal brains (5 males and 5 females/group) from both control and e-cig-exposed groups were used for experimental analysis. Results indicated that prenatal e-cig exposure altered site-specific DNA methylation patterns at both CpG and CH (non-CpG) sites, predominantly in intergenic and intronic regions, with sex dimorphism in methylation and gene expression changes. Gene ontology analysis revealed that e-cig exposure not only affected neuron projection development and axonogenesis but also altered pathways related to neurodegeneration and long-term depression. These findings provide novel insights into the dynamic changes of CpG and CH methylation induced by e-cig exposure, underscoring the susceptibility of the developing brain to maternal e-cig exposure and its potential implications for developmental disorders and neurodegenerative diseases later in life.