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Chang-Liang Luo,1,* Zhi-Gao Xu,2,* Hao Chen,2 Jia Ji,1 Yu-Hui Wang,1 Wei Hu,1 Kun Wang,3 Wu-Wen Zhang,1 Chun-Hui Yuan,4 Fu-Bing Wang1 1Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China; 2Department of Pathology, Zhongnan Hospital of Wuhan University, Wuhan, China; 3Department of Laboratory Medicine, Hubei Cancer Hospital, Wuhan, China; 4Department of Laboratory Medicine, Wuhan Children’s Hospital, Huazhong University of Science and Technology, Wuhan, China *These authors contributed equally to this work Background: Tissue biopsy-based cancer diagnosis has limitations because of the fact that tumor tissues are in constant evolution and extremely heterogeneous. The current study was aimed to examine whether tumor-educated blood platelets (TEPs) might be a potential all-in-one source for blood-based cancer diagnostics to overcome the limitations of conventional cancer biopsy.Methods: In the present study, we evaluated the expression pattern of MAGI2 antisense RNA 3 (MAGI2-AS3) and ZNFX1 antisense RNA 1 (ZFAS1) in both plasma and platelets of 101 non-small-cell lung cancer (NSCLC) patients. Receiver operating characteristic (ROC) curve was generated to evaluate their diagnostic potential. In addition, epidermal growth factor receptor (EGFR) mutations were detected in DNA and RNA samples of platelets for companion diagnostics.Results: Our results showed that the levels of MAGI2-AS3 and ZFAS1 in both plasma and platelets of NSCLC patients were significantly downregulated than those in healthy controls. A positive correlation of long noncoding RNA expression was observed between platelets and plasma (r=0.738 for MAGI2-AS3, r=0.751 for ZFAS1, respectively). By ROC analysis, we found that molecular interrogation of MAGI2-AS3 and ZFAS1 in TEPs and plasma can offer valuable diagnostic performance for NSCLC patients (area under the ROC curve [AUC]MAGI2-AS3=0.853/0.892, and AUCZFAS1=0.780/0.744 for diagnosing adenocarcinoma and squamous cell carcinoma cases from controls, respectively). Clinicopathologic characteristic analysis further revealed that MAGI2-AS3 level significantly correlated with tumor–node–metastasis (TNM) stage (p=0.001 in TEPs, p=0.003 in plasma), lymph-node metastasis (p=0.016 in TEPs, p=0.023 in plasma), and distant metastasis (p=0.045 in TEPs, p=0.045 in plasma), while ZFAS1 level was only correlated with TNM stage (p=0.005 in TEPs, p=0.044 in plasma). Furthermore, EGFRvIII RNA existed in both TEPs and plasma, but EGFR intracellular mutations cannot be detected in DNA of TEPs isolated from NSCLC.Conclusion: Our data suggested that TEP is a promising source for NSCLC diagnosis and companion diagnostics. Keywords: tumor-educated platelets, lncRNA-MAGI2-AS3, lncRNA-ZFAS1, EGFR mutations, NSCLC

Lianyuan Tao, Chunhui Yuan, Zhaolai Ma, Bin Jiang, Dianrong Xiu Department of General Surgery, Peking University Third Hospital, Beijing, People’s Republic of China Introduction: Pancreatic cancer is a lethal disease with a very poor prognosis. This study investigates survival of patients diagnosed with metastatic pancreatic cancer (mPC) based on local treatment of the primary tumor. Methods: Patients diagnosed with stage IV mPC between 2004 and 2013 were identified from the Surveillance, Epidemiology and End Results (SEER) database. Cancer-specific survival (CSS) and overall survival (OS) were examined. CSS and OS were examined by using the Kaplan–Meier method with the log-rank test. Multivariable survival analyses of CSS and OS were conducted using the Cox proportional hazard model. Results: A total of 28918 patients with mPC were included in this analysis. There were 467 patients who received surgical resection (1.6%) and 28451 patients who did not (98.4%). Patients who were younger than 70 years (odds ratio [OR]=1.45, 95% CI=1.04–2.03, p=0.03), diagnosed from 2004 to 2008 (OR=1.49, 95% CI=1.25–1.80, p50 years (HR=1.25, 95% CI=1.09–1.42, p=0.001), male (HR=1.121, 95% CI=1.09–1.15, p

Cunhua Yuan,1 De Chang,2 Guangming Lu,3 Xiaowei Deng1 1Health Medical Center, 2Department of Respiratory Medicine, General Hospital of Chinese People’s Armed Police Forces, 3Institute of Health Management, Chinese PLA General Hospital, Beijing, People’s Republic of China Abstract: Chronic obstructive pulmonary disease (COPD) is a common chronic disease, and its morbidity and mortality are increasing. There are many studies that have tried to explain the pathogenesis of COPD from genetic susceptibility, to identify the susceptibility of COPD factors, which play a role in early prevention, early detection and the early treatment. However, it is well known that COPD is an inflammatory disease characterized by incomplete reversible airflow limitation in which genes interact with the environment. In recent years, many studies have proved gene polymorphisms and COPD correlation. However, there is less research on the relationship between COPD and genome-wide association study (GWAS), epigenetics and apoptosis. In this paper, we summarized the correlation between gene level and COPD from the following four aspects: the GWAS, the gene polymorphism, the epigenetics and the apoptosis, and the relationship between COPD and gene is summarized comprehensively. Keywords: chronic obstructive pulmonary disease, COPD, genetic polymorphism, genome-wide association study

Xiaowei Deng,1 Cun-hua Yuan,1 De Chang2 1Health Medical Center, 2Department of Respiratory Medicine, General Hospital of Chinese People’s Armed Police Forces, Beijing, People’s Republic of China Background: SERPINA1 gene has been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD), while smoking is a known risk factor for COPD. Little is known on the effect of SERPINA1 gene and its interaction with smoking in the Chinese population. In this study, the effect of SERPINA1 gene polymorphisms on COPD risk and its interaction with smoking status has been investigated.Method: A total of 120 COPD patients and 481 healthy controls were recruited at The Armed Police Corps Hospital. Data on demographic variables, smoking status, history of occupational dust exposure, and allergies were collected. Genotyping for single nucleotide polymorphism’s (SNP) rs1243160, rs2854254, and rs8004738 was performed in all participants.Results: SNP rs8004738 genotype was associated with a significantly higher risk for COPD (odds ratio (OR) =1.835, 95% confidence interval (CI): 1.002–3.360), whereas SNPs rs1243160 and rs2854254 did not exhibit such an association. Smoking habit also significantly increased the risk for COPD (OR =2.306, 95% CI: 1.537–3.459). On stepwise logistic regression analysis, advanced age, smoking, and SNP rs8004738 variant were associated with increased risk for COPD, while female gender and higher educational status decreased the risk. On additive interaction analysis, a significant interactive effect of SNP rs8004738 and smoking was observed in this population (relative excess risk due to interaction =0.478; attributable proportion due to interaction (AP) =0.123; S=1.197).Conclusion: SNP rs8004738 of SERPINA1 gene significantly interacted with smoking status and was associated with a higher risk for COPD in the Chinese population. Keywords: chronic obstructive pulmonary disease (COPD), single nucleotide polymorphism (SNP), smoking, SERPINA1 polymorphism

Zhen Qu,1,* Chun-Hui Yuan,2,* Chang-Qing Yin,1 Qing Guan,2 Hao Chen,1 Fu-Bing Wang1 1Department of Laboratory Medicine and Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, 2Department of Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, People’s Republic of China *These authors contributed equally to this work Abstract: Many long noncoding RNAs (lncRNAs) have been reported to be abnormally expressed in hepatocellular carcinoma (HCC), and may have the potential to serve as prognostic markers. In this study, a meta-analysis was conducted to systematically evaluate the prognostic value of various lncRNAs in HCC. Eligible literatures were systematically collected from PubMed, Embase, Web of Science, and Cochrane Library (up to December 30, 2015). The main outcomes including overall survival, relapse-free survival, and disease-free survival were analyzed. Pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated using random- or fixed-effects models. A total of 2,991 patients with HCC in People’s Republic of China from 27 studies were included in the analysis. The level of lncRNAs showed a significant association with clinical outcomes. Abnormally elevated lncRNA transcription level predicted poor overall survival (HR: 1.68, 95% CI: 1.20–2.34, P=0.002; I2=75.5%, P=0.000) and relapse-free survival (HR: 2.08, 95% CI: 1.65–2.61, P

During the boll formation stage, cotton bolls exhibit the lowest expression of Bacillus thuringiensis (Bt) insecticidal proteins. Resistance to insects varies notably among different organs, which poses challenges for controlling cotton bollworms. Consequently, an experimental strategy was designed in the 2020–2021 cotton growing season to coordinate the enhancement of protein synthesis and the attenuation of degradation. Two Bt cultivars of Gossypium hirsutum, namely the hybrid Sikang 3 and the conventional Sikang 1, were used as test materials. Three treatments were applied at the peak flowering period: CK (the control), T1 (amino acids), and T2 (amino acids and EDTA). The results show that, in comparison to the CK group, the Bt protein contents were significantly increased in both cotton bolls and their subtending leaves under the T1 and T2 treatments. The maximum levels of increase observed were 67.5% in cotton bolls and 21.7% in leaves. Moreover, the disparity in Bt protein content between cotton bolls and their subtending leaves notably decreased by 31.2%. Correlation analysis suggested that the primary physiological mechanisms for augmenting Bt protein content involve increased protein synthesis and reduced protein catabolism, which are independent of Bt gene expression levels. Stepwise regression and path analysis revealed that elevating the soluble protein content and transaminase activity, while reducing the catabolic enzyme activities, are instrumental in enhancing the Bt protein content. Consequently, the coordinated application of amino acids and EDTA emerges as a strategy that can improve the overall resistance of Bt cotton and mitigate the spatiotemporal variations in Bt toxin concentrations in both cotton bolls and leaves.

Cardiovascular disease is a significant cause of death in humans. Various models are necessary for the study of cardiovascular diseases, but once cellular and animal models have some defects, such as insufficient fidelity. As a new technology, organoid has certain advantages and has been used in many applications in the study of cardiovascular diseases. This article aims to summarize the application of organoid platforms in cardiovascular diseases, including organoid construction schemes, modeling, and application of cardiovascular organoids. Advances in cardiovascular organoid research have provided many models for different cardiovascular diseases in a variety of areas, including myocardium, blood vessels, and valves. Physiological and pathological models of different diseases, drug research models, and methods for evaluating and promoting the maturation of different kinds of organ tissues are provided for various cardiovascular diseases, including cardiomyopathy, myocardial infarction, and atherosclerosis. This article provides a comprehensive overview of the latest research progress in cardiovascular organ tissues, including construction protocols for cardiovascular organoid tissues and their evaluation system, different types of disease models, and applications of cardiovascular organoid models in various studies. The problems and possible solutions in organoid development are summarized.

Abstract Conventional magnetic biosensing technologies have reduced analytical capacity for magnetic field dimensionality and require extensive sample processing. To address these challenges, we spatially engineer 3D magnetic response gradients for direct and programmable molecular detection in native biofluids. Named magnetic augmentation through triple-gradient coupling for high-performance detection (MATCH), the technology comprises gradient-distributed magnetic nanoparticles encapsulated within responsive hydrogel pillars and suspended above a magnetic sensor array. This configuration enables multi-gradient matching to achieve optimal magnetic activation, response and transduction, respectively. Through focused activation by target biomarkers, the platform preferentially releases sensor-proximal nanoparticles, generating response gradients that complement the sensor’s intrinsic detection capability. By implementing an upstream module that recognizes different biomarkers and releases universal activation molecules, the technology achieves programmable detection of various circulating biomarkers in native plasma. It bypasses conventional magnetic labeling, completes in

Abstract Weathering features of sandstone heritage can be recognized by using artificial intelligence (AI) based surrogate models, and most models perform classification tasks for types based on precise labels. But there are lack of prior validated knowledge of the weathering or untagged historical data for complex weathering conditions in many cases. To this aim, a unsupervised graph neural network (GNN) based on the statistical features of the acoustic emission (AE) signals is constructed. Firstly, taking unweathered sandstone as a reference, we define 4 weathering levels of sandstone ranging from I to IV based on pore indicators. We selected 11 statistical features that are high correlated with pore of sandstone. Then, this GNN is constructed and trained by 2880 sets of statistical measured AE signals. Compared with AEs, LOF and IF models, GNN achieves the best identification performance among the four evaluation criteria. Each iteration of the GNN network is fitting the feature information of the signals and their neighbors. By data dimensionality reduction techniques, when the GNN stops iterating, it will be easy to distinguish unweathered AE signals from weathered one by comparing the reconstruction error of each signal. Furthermore, when the nearest neighbor’s k gradually increases, the AUC of GNN also gradually increases and then tend to stable when k equals to 50–100. While the hidden layers of the network aggregates less information about the neighborhood features of the signals and cannot distinguish significantly between unweathered and weathered signals when the value of k is small. As the depth of the network deepens, the feature values between signals become more and more similar, their reconstruction errors in the output layer of the network to become more similar, making it difficult to distinguish unweathered AE signals from weathered AE signals via GNN. Meanwhile, GNN adopts more AE features and considers the similarity between each features. This can greatly eliminate various errors caused by wave velocity measurement, greatly improving the robustness of AE detection. Hence, the GNN model presented addresses the limitations of relying solely on P-wave velocity measurements to assess the degree of sandstone weathering at stone cultural heritage.

Abstract Objective To analyzed the safety and efficacy of percutaneous nephrolithotomy (PCNL) in lateral decubitus position and prone position for upper ureteral calculi. Methods Databases including PubMed, Springer, ScienceDirect, Wiley Online Library, CNKI, CSPD and VIP were searched for clinical controlled studies involved with lateral decubitus position and prone position PCNL from their establishment to November 2023.Studies were enrolled according to inclusion and exclusion criteria. the dates were compared by Review Manager 5.4 software. Results seven studies were eligible, including 807 cases. The Meta-analysis showed that, blood loss and perioperative complication rate of lateral decubitus position PCNL group were significantly different from those of the prone position PCNL group (P 0.05).Conclusions The lateral decubitus position can reduce blood loss and perioperative complication rate. The lateral decubitus position PCNL is safe and effective for upper ureteral calculi which was deserved clinical popularizing use.

Abstract Background Drug-induced liver injury (DILI) is gradually becoming a common global problem that causes acute liver failure, especially in acute hepatic damage caused by acetaminophen (APAP). Paeoniflorin (PF) has a wide range of therapeutic effects to alleviate a variety of hepatic diseases. However, the relationship between them is still poorly investigated in current studies. Purpose This work aimed to explore the protective effects of PF on APAP-induced hepatic damage and researched the potential molecular mechanisms. Methods C57BL/6J male mice were injected with APAP to establish DILI model and were given PF for five consecutive days for treatment. Aiming to clarify the pharmacological effects, the molecular mechanisms of PF in APAP-induced DILI was elucidated by high-throughput and other techniques. Results The results demonstrated that serum levels of ALP, γ-GT, AST, TBIL, and ALT were decreased in APAP mice by the preventive effects of PF. Moreover, PF notably alleviated hepatic tissue inflammation and edema. Meanwhile, the results of TUNEL staining and related apoptotic factors coincided with the results of transcriptomics, suggesting that PF inhibited hepatocyte apoptosis by regulated MAPK signaling. Besides, PF also acted on reactive oxygen species (ROS) to regulate the oxidative stress for recovery the damaged mitochondria. More importantly, transmission electron microscopy showed the generation of autophagosomes after PF treatment, and PF was also downregulated mTOR and upregulated the expression of autophagy markers such as ATG5, ATG7, and BECN1 at the mRNA level and LC3, p62, ATG5, and ATG7 at the protein level, implying that the process by which PF exerted its effects was accompanied by the occurrence of autophagy. In addition, combinined with molecular dynamics simulations and western blotting of MAPK, the results suggested p38 as a direct target for PF on APAP. Specifically, PF-activated autophagy through the downregulation of MAPK/mTOR signaling, which in turn reduced APAP injury. Conclusions Paeoniflorin mitigated liver injury by activating autophagy to suppress oxidative stress and apoptosis via the MAPK/mTOR signaling pathway. Taken together, our findings elucidate the role and mechanism of paeoniflorin in DILI, which is expected to provide a new therapeutic strategy for the development of paeoniflorin. Graphical abstract

The advent of 3D printing (3DP) has garnered significant interest from both academia and industry due to its potential to revolutionize engineering, manufacturing, and through its utilization of advanced materials. Even though the application of 3D printing in footwear design and manufacture is quite appreciated, academic discourse on the subject relative to footwear design and manufacture is rather scarce compared to other fields such as pharmaceuticals, electronics and food. The purpose of this review is to explore the techniques, the application trends and the impact of 3D printing technology concerning footwear design and manufacture. Using relevant data from many relevant sources, this study uncovered that 3D printing has significantly impacted shoe design and manufacture by enhancing production efficiency, environmental sustainability, material innovation and Inter-Industry Collaborative Projects among others. Most of the major players in the footwear industry such as Nike, Adidas, Reebok and New Balance already have many footwear releases based on 3D printing. Also discussed are some specific areas in which 3D printing is being applied in footwear design and manufacture. These areas include but are not limited to the design of smart shoes, shoe lasts, complex shoe geometries, avant-garde concept shoes and so on. This study is of particular importance to stakeholders in the footwear research and design industry as it provides important information about the current trends as well as the impact of 3D printing technology on the sector.

Magnesium-based biomaterials (MBMs) are one of the most promising materials for tissue engineering due to their unique mechanical properties and excellent functional properties. This review describes the development, advantages, and challenges of MBMs for biomedical applications, especially for tissue repair and regeneration. The history of the use of MBMs from the beginning of the 20th century is traced, and the transformative advances in contemporary applications of MBMs in areas such as orthopedics and cardiovascular surgery are emphasized. The review also provides insight into the signaling pathways affected by MBMs, such as the PI3K/Akt and RANKL/RANK/OPG pathways, which are critical for osteogenesis and angiogenesis. The review advocates that future research should focus on optimizing alloy compositions, surface modification and exploring innovative technologies such as 3D printing to improve the efficacy of MBMs in complex tissue repair. The potential of MBMs to tissue engineering and regenerative medicine is significant, urging further exploration and interdisciplinary collaboration to maximize their therapeutic effects.

Abstract Background Chronic thromboembolic pulmonary hypertension (CTEPH) is a type of pulmonary hypertension with a low incidence. Despite pulmonary endarterectomy(PEA) being the preferred treatment for CTEPH, for patients who failed medical therapy and who are not suitable candidates for PEA, lung transplantation (LT) is still the only effective treatment for end-stage CTEPH; however, there are currently very few reports on the efficacy of LT for CTEPH. Methods We retrospectively analyzed the clinical data of seven patients diagnosed with CTEPH between July 2019 and July 2021. The follow-up deadline was March, 2022. Results The mean age at admission was 54 ± 12 years. The average value of mean pulmonary artery pressure (mPAP) was 40 ± 5 mmHg. The mean preoperative oxygenation index(PaO2/FiO2) was 203 ± 56 mm Hg. After evaluation, one patient underwent left LT and the rest underwent bilateral LT. Three patients received intraoperative veno-venous extracorporeal membrane oxygenation (ECMO) support, and four patients received intraoperative veno-arterial ECMO support. The average postoperative mPAP was 19 ± 4 mmHg. The mean postoperative oxygenation index(PaO2/FiO2) was 388 ± 83 mmHg. There was a significant difference between the preoperative and postoperative mPAP and oxygenation index(PaO2/FiO2). All patients recovered well and were discharged 37 ± 19 days postoperatively. The mean follow-up duration was 19 ± 8 months. There was no recurrence of CTEPH. Conclusions LT is an effective treatment for end-stage CTEPH, which can improve cardiopulmonary function and quality of life and prolong survival. Patients who are unable to tolerate PEA should be considered for LT as early as possible when internal medicine failed.

Abstract The global spread of H5 clade 2.3.4.4 highly pathogenic avian influenza (HPAI) viruses threatens poultry and public health. The continuous circulation of these viruses has led to their considerable genetic and antigenic evolution, resulting in the formation of eight subclades (2.3.4.4a–h). Here, we examined the antigenic sites that determine the antigenic differences between two H5 vaccine strains, H5-Re8 (clade 2.3.4.4g) and H5-Re11 (clade 2.3.4.4h). Epitope mapping data revealed that all eight identified antigenic sites were located within two classical antigenic regions, with five sites in region A (positions 115, 120, 124, 126, and 140) and three in region B (positions 151, 156, and 185). Through antigenic cartography analysis of mutants with varying numbers of substitutions, we confirmed that a combination of mutations in these eight sites reverses the antigenicity of H5-Re11 to that of H5-Re8, and vice versa. More importantly, our analyses identified H5-Re11_Q115L/R120S/A156T (H5-Re11 + 3) as a promising candidate for a broad-spectrum vaccine, positioned centrally in the antigenic map, and offering potential universal protection against all variants within the clade 2.3.4.4. H5-Re11 + 3 serum has better cross-reactivity than sera generated with other 2.3.4.4 vaccines, and H5-Re11 + 3 vaccine provided 100% protection of chickens against antigenically drifted H5 viruses from various 2.3.4.4 antigenic groups. Our findings suggest that antigenic regions A and B are immunodominant in H5 viruses, and that antigenic cartography-guided vaccine design is a promising strategy for selecting a broad-spectrum vaccine.

Abstract The existing diagnostic methods of epilepsy have great limitations, and more reliable and less difficult diagnostic methods are needed. We collected serum samples of adult patients with first-diagnosed epilepsy (EPs) and seizure control patients (EPRs) for non-targeted metabolomics detection and found that they were both significantly altered, with increased expression of nicotine addiction, linoleic acid metabolism, purine metabolism, and other metabolic pathways. The diagnostic model based on 4 differential metabolites achieved a diagnostic efficiency of 99.4% in the training cohort and 100% in the validation cohort. In addition, the association analysis of oral flora, serum metabolism, and clinical indicators also provided a new angle to analyze the mechanism of epilepsy. In conclusion, this study characterized the serum metabolic characteristics of EPs and EPRs and the changes before and after epilepsy control based on a large cohort, demonstrating the potential of metabolites as non-invasive diagnostic tools for epilepsy.

Mustard essential oil (MEO) nanoemulsions fortified with citrus pectin and tween-80 (MEO-NE-PT) or tween-80 (MEO-NE-T) were prepared by high-pressure homogenization followed by ultrasonication, and comparative analysis was performed on the microstructure, storage stability, pH, ionic strength and thermal tolerance between MEO-NE-PT and MEO-NE-T. The application of MEO-NE-PT to the postharvest preservation of ‘Shatangju’ mandarin was evaluated. It was found that MEO-NE-PT exhibited superior stability with smaller fluctuations in particle size and polydispersity index (PDI). The minimum inhibitory concentration (MIC) of MEO-NE-PT was 64 μL/L, much lower than those of MEO (256 μL/L) and MEO-NE-T (128 μL/L). Furthermore, after MEO-NE-PT treatment at 64 μL/L for 6 h, the germination rate of Geotrichum candidum spores was only 6.67%, and the length of the germ tube was only 8.57 μm, both significantly lower than 100% and 165.02 μm for the control group (MEO), respectively. The results of scanning electron microscopy (SEM) revealed that treatment with MEO-NE-PT caused the mycelium of Geotrichum candidum to wrinkle and break apart. Compared with the control group, MEO-NE-PT treatment could significantly reduce the decay rate and quality loss of ‘Shatangju’ mandarin, while delaying the decline in hardness and total soluble solids. As a safe and effective antimicrobial agent, MEO-NE-PT could control the growth of Geotrichum candidum and maintain the post-harvest quality of ‘Shatangju’ mandarin.

Abstract Background Sudden temperature drops, resulting from extreme weather events, often occur during the boll-setting period of cotton in Xinjiang, China, causing decreased expression of Bacillus thuringiensis (Bt) insecticidal proteins in cotton bolls. The precise threshold temperatures and durations that lead to significant changes in Cry1Ac endotoxin levels under low temperatures remain unclear. To address this, we investigated the effects of different temperatures and stress durations on Cry1Ac endotoxin levels in cotton bolls. In 2020–2021, two Bt transgenic cotton varieties, conventional Sikang1 and hybrid Sikang3, were selected as experimental materials. Various low temperatures (ranging from 16 to 20 °C) with different durations (12 h, 24 h and 48 h) were applied during the peak boll-setting period. Results As the temperature decreased, the Cry1Ac endotoxin content in the boll shell, fiber, and seed exhibited a declining trend. Moreover, the threshold temperature which caused a significant reduction in Cry1Ac endotoxin content increased with the prolonged duration of low-temperature stress. Among the components of cotton bolls, seeds were most affected by low-temperature stress, with the threshold temperature for a significant reduction in Cry1Ac endotoxin content ranging from 17 °C to 19 °C. Correlation analysis indicated that low temperatures led to a decrease in protein synthesis capacity and an increase in degradation ability, resulting in reduced Cry1Ac endotoxin content. Pathway analysis revealed that both free amino acid and peptidase had significant negative effects on Cry1Ac endotoxin content. Conclusion In summary, when the daily average temperature was ≤ 19 °C, implementing cultural practices to reduce free amino acid content and peptidase activity could serve as effective cold defense strategies for Bt cotton production.

Abstract Endometrial cancer (EC) is associated with significant risk factors such as polycystic ovarian syndrome (PCOS) and sedentary behavior. In our study, we aim to employ machine learning algorithms to investigate the potential molecular processes that underlie their interaction and explore their respective roles in the diagnosis and immunotherapy of EC. The GEO database provides access to microarray data, which was utilized in this study to identify gene expression modules associated with PCOS and sedentary behavior, using weighted gene expression network analysis (WGCNA). Cluego software was then employed to investigate the energy enrichment of shared pathways in both PCOS and sedentary individuals, and differential gene analysis was used to confirm another two databases. The miRNAs–mRNAs controlled network was constructed to verify the pathway. The immune-related factors of the shared pathway in EC were then analyzed. Finally, to validate our findings, we conducted cell experiments using EC cell lines (AN3CA, KLE, Ishikawa, RL95-2, and HEC-1A). We found that increased intracellular aromatic compound anabolism is a common feature of both PCOS and sedentary individuals. We then developed a disease pathway model that was based on the common genetic characteristics of PCOS and sedentary behavior. We utilized pathway typing in EC samples and found a significant survival difference between the two subgroups, with the upregulated expression type exhibiting an immune-hot phenotype. Finally, the experimental results confirmed the expression of the hub gene (NAA15) in EC. The findings of our study suggest that genes related to the intracellular aromatic compound metabolic pathway can be used for immunotherapy of EC.

In order to investigate the influence of antifreeze peptide properties on its protective effect on myofibrillar proteins in frozen surimi, the present study was conducted to characterize the properties of three antifreeze peptides (sericin peptides, collagen peptides and silver carp hydrolysates), and we analyzed the changing pattern of myofibrillar protein properties under different freezing conditions, and constructed a correlation model between myofibrillar protein properties and frozen storage parameters and antifreeze peptide properties using least absolute shrinkage and selection operator (Lasso) regression. The results showed that all antifreeze peptides used in the study were “hyperactive” antifreeze peptides with thermal hysteresis activity (THA) (> 0.60 ℃), low molecular mass (< 10 000 Da), high hydrophilicity (θ < 30°) , and polar amino acid content of more than 60%; the antifreeze peptides were able to significantly mitigate the negative effects of frozen storage on myofibrillar proteins. The mean content of myofibrillar proteins in frozen surimi with added antifreeze peptides was 50.44–54.47 mg/g, the mean Ca2+-ATPase activity was 1.61–1.67 U/mg, the mean surface hydrophobicity index increased only by 39.91%–42.40% when compared with that of fresh surimi, and the rate of myofibrillar protein denaturation was much lower than that of the control group without antifreeze peptides. The Lasso regression model explained the effects of antifreeze peptide properties on changes in the properties of myofibrillar protein in frozen surimi, demonstrating that antifreeze peptides with lower molecular mass and higher THA contributed to slowing down the decline in myofibrillar protein content, Ca2+-ATPase activity, surface hydrophobicity, and characteristic indexes. The differences in the hydrophilicity/hydrophobicity of antifreeze peptides resulted in differences in their interactions with ice crystals and proteins, and consequently caused different effects on surimi myofibrillar proteins. This study provides a theoretical basis for the application of antifreeze peptides and the quality regulation of surimi products and also provides a direction for the development of novel efficient antifreeze agents.

Abstract The Weixinan Sag in Beibuwan Basin is a pilot area of the offshore exploration and development integrated technology. The main oil bearing layers, first member of Liushagang formation and third member of Weizhou formation, develop many fault systems and structural traps. The key factors of the offshore exploration and development integrated technology are”the fault research”and “the effectiveness of structural trap”. Fault research includes the study of the geometry, dynamics, kinematics characteristics of fault, and the division of fault system. The effectiveness of structural trap include analogical studies on the structural characteristics of traps, quantitative studies on fault lateral sealability, fault vertical sealability, and prediction technology of oil column height. Synthesizing the relationship of the law of oil and gas distribution,the differential fault system in the internal of the No. 2 fault zone, and the effectiveness research of traps, the fault-controlled reservoir laws and the dominant fault-controlled reservoir mode are obtained. The research on fault and trap of offshore integrated exploration and development has been successfully applied in the Weixinan Sag. The 37 of 45 development evaluation wells have been drilled successfully and the drilling success rate is 82%. It has promoted the ODP(original drilling project) implementation of 5 oilfields, the adjustment implementation of 8 oilfields and made important contribution to the increase of reserves and production in the Weixinan Sag.

Abstract Objective In 2016, the ESMO-ESGO-ESTRO consensus included LVSI (Lymph-vascular space invasion, LVSI) status as a risk stratification factor for stage I endometrioid endometrial cancer (EEC) patients and as one of the indications for adjuvant therapy. Furthermore, LVSI is included in the new FIGO staging of endometrial cancer (EC) in 2023. However, the data contribution of the Chinese population in this regard is limited. The present study aimed to further comfirm the influence of LVSI on the prognosis of early-stage low-grade EEC in a fifteen-year retrospective Chinese cohort study. Methods This retrospective analysis cohort included 702 EEC patients who underwent TAH/BSO surgery, total abdominal hysterectomy, bilateral salpingooophorectomy in Peking University People’s Hospital from 2006 to 2020. Patients were stratified based on LVSI expression status as: LVSI negative group and LVSI positive group. Clinical outcome measures related to LVSI, assessed with a univariate and multivariate Cox proportional hazards regression model. Results 702 EEC patients with stage I and grade 1–2 were analyzed. 58 patients (8.3%) were LVSI-positive and 14 patients (2.0%) was relapse. Recurrence rates in LVSI-negative and LVSI-positive were 1.6% and 6.9%, respectively. 5-year disease-free survival (DFS) rate in LVSI-negative and LVSI-positive were 98.4% and 93.1%, respectively. These rates for 5-year overall (OS) survival in LVSI-negative were 98.9% while it was 94.8% in LVSI-positive. Multivariate analysis showed that LVSI is an independent risk factor for 5-year DFS (HR = 4.60, p = 0.010). LVSI has a similar result for 5-year OS(HR = 4.39, p = 0.028). Conclusions LVSI is an independent predictor of relapse and poor prognosis in early-stage low-grade endometrioid endometrial cancer in the Chinese cohort.

Abstract Background In recent years, global climate change in tandem with increased human activity has resulted in habitat degradation or the migration of rare medicinal plants, potentially impacting the quality of medicinal herbs. Astragalus membranaceus var. mongholicus is a valuable bulk medicinal material in Northwest China. As the demand for this medicinal herb continues to increase in both domestic and international markets, ensuring the sustainable development of high-quality Astragali Radix is important. In this study, the maximum entropy (Maxent) model was applied, thereby incorporating 136 distribution records, along with 39 environmental factors of A. membranaceus var. mongholicus, to assess the quality zonation and potential distribution of this species in China under climate change. Results The results showed that the elevation, annual mean temperature, precipitation of wettest month, solar radiation in June, and mean temperature of warmest quarter were the critical environmental factors influencing the accumulation of astragaloside IV and Astragalus polysaccharide in A. membranaceus var. mongholicus. Among the twelve main environmental variables, annual mean temperature, elevation, precipitation of the wettest month, and solar radiation in November were the four most important factors influencing the distribution of A. membranaceus var. mongholicus. In addition, ecological niche modelling revealed that highly suitable habitats were mainly located in central and western Gansu, eastern Qinghai, northern Shaanxi, southern Ningxia, central Inner Mongolia, central Shanxi, and northern Hebei. However, the future projections under climate change suggested a contraction of these suitable areas, shifting towards northeastern high-latitude and high-elevation mountains. Conclusions The findings provide essential insights for developing adaptive strategies for A. membranaceus var. mongholicus cultivation in response to climate change and can inform future research on this species. By considering the identified environmental factors and the potential impacts of the predicted climate changes, we can visualize the regional distribution of high-quality Radix Astragali and develop conservation strategies to protect and restore its suitable habitats.

Abstract To explore the role of bronchoscopy for the assessment of checkpoint inhibitor pneumonitis (CIP), a retrospective single-center study was conducted to assess patients diagnosed with CIP at grade 2 or above and also underwent bronchoscopy between January 2020 and December 2022. Clinical data and bronchoscopic findings were recorded. The treatment data and prognosis information were collected. Twenty-one patients who underwent bronchoscopy and were diagnosed with CIP were enrolled in this study. All patients underwent bronchoalveolar lavage fluid (BALF) analysis. Of them, T lymphocyte subsets of BALF were tested in 15 cases. Transbronchial cryobiopsy (TBCB) was performed in 8 patients, and transbronchial lung biopsy was performed in 5 patients. 3 patients developed pneumothorax after TBCB and all recovered without serious compilations.14 patients experienced grade 2 CIP, while 7 patients ≥ grade 3 CIP. Symptoms were improved in 19 (90.5%) patients after standard treatment adhering to CIP guidelines. However, 5 patients relapsed during steroid tapering. Factors related to the severity and recurrence of CIP were analyzed. Patients with previous interstitial lung disease (ILD) were more likely to develop high grade CIP than those without [83.3% (5/6) versus 15.4% (3/15), P = 0.011].The odds ratio (OR) was 32.5 (95% CI 2.284–443.145, P = 0.009). Increased BALF lymphocyte percentage was associated with high grade CIP, OR 1.095 (95% CI 1.001–1.197, P = 0.047), and higher possibility of CIP relapse, OR 1.123 (95% CI, 1.005–1.225, P = 0.040). Lymphocyte subsets were tested in 15 patients. CD4/CD8 > 1 was found in 80% (4/5) of relapsed patients and 20% (2/10) of patients without relapse (P = 0.047). The OR was 16.00 (95% CI 1.093–234.24, P = 0.043). In this retrospective study, patients with previous ILD was more likely to develop high grade CIP. Higher lymphocyte percentage in BALF was associated with high grade CIP and susceptibility to relapse during treatment of CIP. A CD4/CD8 ratio greater than 1 in lymphocyte subsets of BALF was associated with higher possibility of CIP relapse. We found that TBCB is a safe procedure in CIP patients.

Abstract In order to predict the damage behaviours of 3D-printed continuous carbon fibre (CCF) reinforced composites, when additional short carbon fibre (SCF) composite components are employed for continuous printing or special functionality, a novel path-dependent progressive failure (PDPF) numerical approach is developed. First, a progressive failure model using Hashin failure criteria with continuum damage mechanics to account for the damage initiation and evaluation of 3D-printed CCF reinforced polyamide (PA) composites is developed, based on actual fibre placement trajectories with physical measurements of 3D-printed CCF/PA constituents. Meanwhile, an elastic-plastic model is employed to predict the plastic damage behaviours of SCF/PA parts. Then, the accuracy of the PDPF model was validated so as to study 3D-printed CCF/PA composites with either negative Poisson’s ratio or high stiffness. The results demonstrate that the proposed PDPF model can achieve higher prediction accuracies in mechanical properties of these 3D-printed CCF/PA composites. Mechanism analyses show that the stress distribution is generally aggregated in the CCF areas along the fibre placement paths, and the shear damage and matrix tensile/compressive damage are the key damage modes. This study provides a new approach with valuable information for characterising complex 3D-printed continuous fibre-matrix composites with variable mechanical properties and multiple constituents.

Abstract Objective The aim of this study is to identify risk factors associated with acute complicated appendicitis (CA) in children aged three years or younger, providing a theoretical foundation for the management and treatment of acute appendicitis (AA). Methods A retrospective analysis was conducted on 135 pediatric patients with AA, admitted to the Department of General Surgery at Anhui Children’s Hospital between December 2020 and December 2023, who underwent successful surgical treatment. Based on the intraoperative and postoperative pathological findings, patients were categorized into two groups: complicated appendicitis (CA) (n = 97 cases) and uncomplicated appendicitis (UA) (n = 38 cases). Clinical data including gender, age, weight, disease duration, preoperative white blood cell count (WCC), neutrophil granulocyte (NEUT) count, C-reactive protein (CRP) levels, total bilirubin (TBil) levels, procalcitonin (PCT) levels, calprotectin (Cal) levels, preoperative ultrasound results indicating the presence or absence of fecaliths, maximum appendix diameter, and pediatric appendicitis sore (PAS) were collected and analyzed. Comparative analysis was performed to investigate the differences between the groups and identify risk factors of CA. Results The CA group exhibited significantly higher values in disease duration, CRP levels, PCT, Cal, presence of appendiceal fecaliths, maximum appendix diameter, and PAS compared to the UA group (P

Abstract The monitoring of currents in the abyssal ocean is an essential foundation of deep-sea research. The state-of-the-art current meter has limitations such as the requirement of a power supply for signal transduction, low pressure resistance, and a narrow measurement range. Here, we report a fully integrated, self-powered, highly sensitive deep-sea current measurement system in which the ultra-sensitive triboelectric nanogenerator harvests ocean current energy for the self-powered sensing of tiny current motions down to 0.02 m/s. Through an unconventional magnetic coupling structure, the system withstands immense hydrostatic pressure exceeding 45 MPa. A variable-spacing structure broadens the measuring range to 0.02–6.69 m/s, which is 67% wider than that of commercial alternatives. The system successfully operates at a depth of 4531 m in the South China Sea, demonstrating the record-deep operations of triboelectric nanogenerator-based sensors in deep-sea environments. Our results show promise for sustainable ocean current monitoring with higher spatiotemporal resolution.

Abstract The study aims to explore the central genes that Kawasaki disease (KD) and Obesity (OB) may jointly contribute to coronary artery disease. Investigating single-cell datasets (GSE168732 and GSE163830) from a comprehensive gene expression database, we identified characteristic immune cell subpopulations in KD and OB. B cells emerged as the common immune cell characteristic subgroup in both conditions. Subsequently, we analyzed RNA sequencing datasets (GSE18606 and GSE87493) to identify genes associated with B-cell subpopulations in KD and OB. Lastly, a genome-wide association study and Mendelian randomization were conducted to substantiate the causal impact of these core genes on myocardial infarction. Quantitative real-time PCR (qRT-PCR) to validate the expression levels of hub genes in KD and OB. The overlapping characteristic genes of B cell clusters in both KD and OB yielded 70 shared characteristic genes. PPI analysis led to the discovery of eleven key genes that significantly contribute to the crosstalk. Employing receiver operating characteristic analysis, we evaluated the specificity and sensitivity of these core genes and scored them using Cytoscape software. The inverse variance weighting analysis suggested an association between TNFRSF17 and myocardial infarction risk, with an odds ratio of 0.9995 (95% CI = 0.9990–1.0000, p = 0.049). By employing a single-cell combined transcriptome data analysis, we successfully pinpointed central genes associated with both KD and OB. The implications of these findings extend to shedding light on the increased risk of coronary artery disease resulting from the co-occurrence of OB and KD.

Introduction: Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia, and it significantly increases the risk of cardiovascular complications and morbidity, even with appropriate treatment. Tissue remodeling has been a significant topic, while its systematic transcriptional signature remains unclear in AF. Objectives: Our study aims to systematically investigate the molecular characteristics of AF at the cellular-level. Methods: We conducted single-nuclei RNA-sequencig (snRNA-seq) analysis using nuclei isolated from the left atrial appendage (LAA) of AF patients and sinus rhythm. Pathological staining was performed to validate the key findings of snRNA-seq. Results: A total of 30 cell subtypes were identified among 80, 592 nuclei. Within the LAA of AF, we observed a specific subtype of dedifferentiated cardiomyocytes (CMs) characterized by reduced expression of cardiac contractile proteins (TTN and TRDN) and heightened expression of extracellular-matrix related genes (COL1A2 and FBN1). Transcription factor prediction analysis revealed that gene expression patterns in dedifferentiated CMs were primarily regulated by CEBPG and GISLI. Additionally, we identified a distinct subtype of endothelial progenitor cells (EPCs) demonstrating elevated expression of PROM1 and KDR, a population decreased within the LAA of AF. Epicardial adipocytes disclosed a reduced release of the anti-inflammatory and anti-fibrotic factor PRG4, and an augmented secretion of VEGF signals targeting CMs. Additionally, we noted accumulation of M2-like macrophages and CD8+ T cells with high pro-inflammatory score in LAA of AF. Furthermore, the analysis of intercellular communication revealed specific pathways related to AF, such as inflammation, extracellular matrix, and vascular remodeling signals. Conclusions: This study has discovered the presence of dedifferentiated CMs, a decrease in endothelial progenitor cells, a shift in the secretion profile of adipocytes, and an amplified inflammatory response in AF. These findings could offer crucial insights for future research on AF and serve as valuable references for investigating novel therapeutic approaches for AF.

Abstract Post-diagnosis weight gain is common in early-stage breast cancer and is associated with increased risk of recurrence and mortality. Intentional weight loss is difficult to maintain, and digital lifestyle interventions may provide a scalable approach to address this challenge. In this prospective single-arm study (ClinicalTrials.gov NCT04753268; February 15, 2021), key eligibility criteria included: stage I–III breast cancer, body mass index (BMI) ≥ 27.5 kg/m2, and completion of cancer treatment ≥6 months before study enrollment. Participants were provided with a behavioral change mobile application (Noom®). The primary endpoint was a change in self-reported weight from baseline to 26 weeks. Secondary endpoints included engagement, changes in physical activity, dietary patterns, and patient-reported outcomes (PRO). In total, 31 patients were enrolled (mean age 56.8 ± 9.9, mean baseline BMI 33.5 kg/m2 ± 6.5). The mean weight change was −4.8 kg ( ± 4.4, P

Objective To explore the influencing factors the combination of acute renal tubular injury （ARTI） in patients with idiopathic membranous nephropathy （IMN） in a multi-ethnic area of Guangxi. Methods From April 2013 to October 2021, 155 patients with IMN diagnosed by renal biopsy and hospitalized at Hechi People's Hospital were recruited. They were assigned into two groups of with ARTI （n = 43） and without （n = 112）. Results Multifactorial Logistic analysis revealed that serum β2 microglobulin （β2-MG） was independently associated with ARTI in IMN patients （OR = 1.06, 95%CI: 1.01 to 1.12, P = 0.014）. AUC value for ROC curve analysis of serum β2 microglobulin for diagnosing ARTI was 0.748. An optimal threshold value of 2.65 mg/L corresponded to a sensitivity of 81.4% and a specificity of 58.04%. According to serum β2 microglobulin level, they were assigned into three groups of low, medium and high. The odds of ARTI spiked 5.01 and 22.89 folds in medium and high groups as compared with low group. And the results of trend test indicated that the odds of ARTI in IMN patients increased with a rising serum β2 microglobulin concentration （P＜0.001）. Stratified interaction test analysis revealed an interaction between serum β2 microglobulin and ARTI in IMN patients among gender, differential degrees of hypoproteinemia and ethnicity （P for interaction ＜0.05）. Conclusion Serum β2 microglobulin is independently associated with ARTI in IMN patients. And an interaction exists between gender, differential levels of hypoproteinemia and ethnicity.

Objective:. Pancreatic cancer is one of the most aggressive malignancies, a robust prognostic signature and novel biomarkers are urgently needed for accurate stratification of the patients and optimization of clinical decision-making. Methods:. A list of bioinformatic analysis were applied in public dataset to construct an immune-related signature. Furthermore, the most pivotal gene in the signature was identified. The potential mechanism of the core gene function was revealed through GSEA, CIBERSORT, ESTIMATE, immunophenoscore (IPS) algorithm, single-cell analysis, and functional experiment. Results:. An immune-related prognostic signature and associated nomogram were constructed and validated. Among the genes constituting the signature, interleukin 1 receptor type II (IL1R2) was identified as the gene occupying the most paramount position in the risk signature. Meanwhile, knockdown of IL1R2 significantly inhibited the proliferation, invasion, and migration ability of pancreatic cancer cells. Additionally, high IL1R2 expression was associated with reduced CD8+ T cell infiltration in pancreatic cancer microenvironment, which may be due to high programmed cell death-ligand-1 (PD-L1) expression in cancer cells. Finally, the IPS algorithm proved that patients with high IL1R2 expression possessed a higher tumor mutation burden and a higher probability of benefiting from immunotherapy. Conclusion:. In conclusion, our study constructed an efficient immune-related prognostic signature and identified the key role of IL1R2 in the development of pancreatic cancer, as well as its potential to serve as a biomarker for immunotherapy efficacy prediction for pancreatic cancer.

Power components under corrosive environmental conditions are subjected to the double damage of corrosion and wear, and the reciprocating action of the load makes the passivation layer on the metal surface fail and accelerates the damage. Amorphous carbon-based films show the excellent protection in the areas of corrosion and friction. For studying the effect of load on the corrosion and wear properties of amorphous carbon-based thin films, and clarifying the relationship of the each loss component with the change of the load, thin films of a-C, a-C:Cr and a-C:Si were prepared on the surface of 304 stainless steel by magnetron sputtering. Meanwhile, the static corrosion behavior of three films under 5.0 mol/L HNO3 was tested by kinetic potential polarization, and the effect of load on each component of the corrosion friction process was also analyzed and studied by combining the wear amounts of the three films under different loads in deionized water and 5.0 mol/L HNO3 environments. Results showed that Si doping reduced the corrosion current density of a-C films from 1.11×10-6 A/cm2 to 3.96×10-7 A/cm2, while Cr doping slightly decreased the corrosion current density. As the load increased, the corrosion damage component of the three films decreased and the mechanical wear component increased accordingly, corresponding to a weakening of the damage effect on the films due to the corrosion-wear interaction.

Objective The large section tunnel, due to flat shape and large span, usually adopts multiple steps and staged excavation. In the process of construction, the surrounding rock and the temporary support are repeatedly disturbed, affecting the stability of surrounding rock and supporting structure. Therefore, the deformation characteristics of the surrounding rock should be studied and the construction scheme should be optimized. Method Taking the mined tunnel of Qingdao Metro Line 4 in turn-back section as the example, based on the on-site monitoring data and using finite element simulation, the deformation characteristics of the surrounding rock in the excavation process of the large-section metro tunnel with three-step and nine-stage method are analyzed, and then compared with the optimized three-step and five-stage method. Result & Conclusion The simulation results show that the ground settlement is relatively large caused by the current construction scheme within the horizontal distance of 26m from the tunnel center line, accounting for 89.77% of the total settlement. The arch and the spandrel deform are large after excavation, and the maximum settlement reaches 102 mm. The stress of the surrounding rock of the arch increases rapidly with excavation. As the excavation advances, the local principal stress concentration appears in the upper part of the haunch and the corner. The optimized three-step and five-stage excavation method can realize rapid excavation and support, and simplify the construction process by 40%, while reducing disturbance to the surrounding rock and controlling its deformation within a reasonable range of 10 mm. Thus, the stress redistribution of the arch and the stress concentration in the corner are improved.

Abstract Background Whether there are invasive components in pure ground glass nodules(pGGNs) in the lungs is still a huge challenge to forecast. The objective of our study is to investigate and identify the potential biomarker genes for pure ground glass nodule(pGGN) based on the method of bioinformatics analysis. Methods To investigate differentially expressed genes (DEGs), firstly the data obtained from the gene expression omnibus (GEO) database was used.Next Weighted gene co-expression network analysis (WGCNA) investigate the co-expression network of DEGs. The black key module was chosen as the key one in correlation with pGGN. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analyses were done. Then STRING was uesd to create a protein-protein interaction (PPI) network, and the chosen module genes were analyzed by Cytoscape software.In addition the polymerase chain reaction (PCR) was used to evaluate the value of these hub genes in pGGN patients’ tumor tissues compared to controls. Results A total of 4475 DEGs were screened out from GSE193725, then 225 DEGs were identified in black key module, which were found to be enriched for various functions and pathways, such as extracellular exosome, vesicle, ribosome and so on. Among these DEGs, 6 overlapped hub genes with high degrees of stress method were selected. These hub genes include RPL4, RPL8, RPLP0, RPS16, RPS2 and CCT3.At last relative expression levels of CCT3 and RPL8 mRNA were both regulated in pGGN patients’ tumor tissues compared to controls. Conclusions To summarize, the determined DEGs, pathways, modules, and overlapped hub genes can throw light on the potential molecular mechanisms of pGGN.

Abstract The Islamist group ISIS has been particularly successful at recruiting Westerners as terrorists. A hypothesized explanation is their simultaneous use of two types of propaganda: Heroic narratives, emphasizing individual glory, alongside Social narratives, which emphasize oppression against Islamic communities. In the current study, functional MRI was used to measure brain responses to short ISIS propaganda videos distributed online. Participants were shown 4 Heroic and 4 Social videos categorized as such by another independent group of subjects. Persuasiveness was measured using post-scan predictions of recruitment effectiveness. Inter-subject correlation (ISC) was used to measure commonality of brain activity time courses across individuals. ISCs in ventral striatum predicted rated persuasiveness for Heroic videos, while ISCs in mentalizing and default networks, especially in dmPFC, predicted rated persuasiveness for Social videos. This work builds on past findings that engagement of the reward circuit and of mentalizing brain regions predicts preferences and persuasion. The observed dissociation as a function of stimulus type is novel, as is the finding that intersubject synchrony in ventral striatum predicts rated persuasiveness. These exploratory results identify possible neural mechanisms by which political extremists successfully recruit prospective members and specifically support the hypothesized distinction between Heroic and Social narratives for ISIS propaganda.

Abstract In recent years, single-cell analyses have revealed the heterogeneity of the tumour microenvironment (TME) at the genomic, transcriptomic, and proteomic levels, further improving our understanding of the mechanisms of tumour development. Single-cell RNA sequencing (scRNA-seq) technology allow analysis of the transcriptome at the single-cell level and have unprecedented potential for exploration of the characteristics involved in tumour development and progression. These techniques allow analysis of transcript sequences at higher resolution, thereby increasing our understanding of the diversity of cells found in the tumour microenvironment and how these cells interact in complex tumour tissue. Although scRNA-seq has emerged as an important tool for studying the tumour microenvironment in recent years, it cannot be used to analyse spatial information for cells. In this regard, spatial transcriptomics (ST) approaches allow researchers to understand the functions of individual cells in complex multicellular organisms by understanding their physical location in tissue sections. In particular, in related research on tumour heterogeneity, ST is an excellent complementary approach to scRNA-seq, constituting a new method for further exploration of tumour heterogeneity, and this approach can also provide unprecedented insight into the development of treatments for pancreatic cancer (PC). In this review, based on the methods of scRNA-seq and ST analyses, research progress on the tumour microenvironment and treatment of pancreatic cancer is further explained.

Abstract Among middle‐aged and older people, balanced and nutritious diets are the foundation for maintaining bone health and preventing osteoporosis. This study is aimed at investigating the link between dietary folic acid intake and the risk of osteoporosis among middle‐aged and older people. A total of 20,686 people from the National Health and Nutritional Examination Survey (NHANES) 2007–2010 are screened and included, and 5312 people aged ≥45 years with integral data are ultimately enrolled in evaluation. Demographics and dietary intake‐related data are gathered and analyzed, and the odds ratio (OR) and 95% confidence interval (CI) of each tertile category of dietary folic acid intake and each unit increase in folic acid are assessed via multivariate logistic regression models. On this basis, the receiver operating characteristic (ROC) curve is used to identify the optimal cutoff value of dietary folic acid intake for indicating the risk of osteoporosis. Of 5312 people with a mean age of 62.4 ± 11.0 years old, a total of 513 people with osteoporosis are screened, and the dietary folic acid intake amount of the osteoporosis group is significantly lower than that of the non‐osteoporosis group (p

In order to obtain a green and efficient preparation process for carboxymethyl porous starch, carboxymethyl porous starch was prepared by mechanical activation solid phase etherification method, where enzymatically hydrolyzed porous cassava starch was used as raw material, sodium chloroacetate as etherifying agent, and sodium hydroxide as catalyst. Single-factor experiments were conducted to explore the effects of various factors on the degree of substitution (DS) of carboxymethyl porous starch, and the application of carboxymethyl porous starch in soy sauce was discussed. The results showed that the optimal process conditions for the preparation of carboxymethyl porous starch by mechanical activation and solid phase synthesis method were as follows: The molar ratio of porous starch to sodium chloroacetate was 1:1, the mass fraction of sodium hydroxide was 18.8%, the ball milling time was 1.5 h, and the reaction temperature was 50℃. Under these conditions, the highest DS of carboxymethyl porous starch obtained was up to 0.2532. Furthermore, the carboxymethylation reaction of porous starch was confirmed by infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), and scanning electron microscopy (SEM). With the increase of DS of carboxymethyl porous starch, its cold water solubility, water absorption, and adsorption of lemon yellow increased. When DS was 0.2532, the cold water solubility of carboxymethyl porous starch reached 64.94%, the water absorption rate reached 180.73%, and the adsorption amount of lemon yellow reached 2.5086 mg·g−1. The powder soy sauce prepared by carboxymethyl porous starch has better solubility, lower moisture absorption, and higher content of amino acid nitrogen, and is closer to the original soy sauce compared to those prepared by cassava starch and porous starch. Therefore, the mechanical activation and solid phase etherification method can effectively prepare carboxymethyl porous starch, which is simple to operate, environmentally friendly, and highly substitutive, providing a scientific basis for the development and utilization of porous starch.

Abstract The KEYNOTE-522 (KN522) regimen for neoadjuvant treatment of triple negative breast cancer (TNBC) utilized q3week dosing for doxorubicin plus cyclophosphamide (AC); however, dose-dense AC (ddAC) has demonstrated superior overall survival (OS) compared to q3week AC in anthracycline and taxane-based regimens. We performed a retrospective analysis assessing the use of ddAC in KN522 and the impact of sequencing ddAC before or after carboplatin/paclitaxel (CbT) plus pembrolizumab on multiple outcomes. 128 patients with TNBC were included. Overall pathologic complete response (pCR) rate of 56%. Sequencing of ddAC vs CbT first showed no difference in pCR rate (ddAC 55% vs. CbT 58%, p = 0.77). However, ddAC first compared to CbT first correlated with a significant increase in the incidence of overall treatment delays (ddAC 70% vs. CbT 51%, p = 0.03), with cytopenias most frequent (ddAC 59% vs. CbT 31%, p = 0.001). ddAC in a modified KN522 regimen is safe, tolerable, and effective. Efficacy is comparable regardless of chemotherapy sequencing, but ddAC first is significantly associated with higher rates of treatment delays and cytopenias.

Background: Spinal cord injury (SCI) is a severe impairment of the central nervous system, leading to motor, sensory, and autonomic dysfunction. The present study investigates the efficacy of the polyethylene glycol (PEG)-mediated spinal cord fusion (SCF) techniques, demonstrating efficacious in various animal models with complete spinal cord transection at the T10 level. This research focuses on a comparative analysis of three SCF treatment models in beagles: spinal cord transection (SCT), vascular pedicle hemisected spinal cord transplantation (vSCT), and vascularized allograft spinal cord transplantation (vASCT) surgical model. Methods: Seven female beagles were included in the SCT surgical model, while four female dogs were enrolled in the vSCT surgical model. Additionally, twelve female dogs underwent vASCT in a paired donor-recipient setup. Three surgical model were evaluated and compared through electrophysiology, imaging and behavioral recovery. Results: The results showed a progressive recovery in the SCT, vSCT and vASCT surgical models, with no statistically significant differences observed in cBBB scores at both 2-month and 6-month post-operation (both P>0.05). Neuroimaging analysis across the SCT, vSCT and vASCT surgical models revealed spinal cord graft survival and fiber regrowth across transection sites at 6 months postoperatively. Also, positive MEP waveforms were recorded in all three surgical models at 6-month post-surgery. Conclusion: The study underscores the clinical relevance of PEG-mediated SCF techniques in promoting nerve fusion, repair, and motor functional recovery in SCI. SCT, vSCT, and vASCT, tailored to specific clinical characteristics, demonstrated similar effective therapeutic outcomes.

Heat performance and internal pressure loss are important reference standards in solar air heaters (SAH). In order to solve the problem of too large a pressure loss in SAH, an innovative SAH with sinusoidal baffles was proposed on the basis of folded baffle and semi-circular baffle air heaters. A computational fluid dynamics (CFD) simulation calculation was performed for the SAH with sinusoidal baffles, and the relevant parameters, such as the heat collection efficiency and the pressure loss, were analyzed. The results showed that the sinusoidal baffle had a better heat collection performance and a smaller pressure loss compared to the folded baffle and the semi-circular baffle. A sinusoidal baffle can further improve the thermal performance of SAH. The simulation calculation of wave lengths for sinusoidal baffles revealed that when the wavelength value was 200 mm, the SAH had the best heat collection effect, and the heat collection efficiency was 64.49%. On the basis of determining the wavelength, the wave height of the sinusoidal baffle was studied. When the wave height was 30 mm, the minimum pressure loss of the SAH was 17.51 Pa, and the maximum heat collection efficiency was 64.91%. Analyses and research on the Reynolds number of the air inlet showed that as the Reynolds number increased, the collection efficiency and internal pressure loss gradually increased, while the outlet temperature decreased. The curve fitting of the imported Reynolds number and the pressure loss showed that the accuracy of pressure loss fitting curve is 0.997. Research on a double-layer SAH showed that the cross different inlet (CDI) had the best collector performance. This research has a high practicality and can provide a theoretical basis for winter air heating.

Abstract Introduction This study aimed to explore influencing factors and clinical significance of ultra-long-term microischemia following intracranial aneurysm (IA) embolization and establish a theoretical foundation for reducing both the incidence of ultra-long-term microischemia and cognitive dysfunction in patients post embolization. Methods A retrospective analysis was conducted on data from 147 patients who received endovascular treatment for IAs. Patients were categorized into microischemic and control (non-microischemic) groups on the based on the findings of high-resolution magnetic resonance vessel wall imaging (HR-VWI) examinations performed 3 days postoperatively and 6 months postoperatively. Risk factors for the occurrence of ultra-long-term microischemia were determined by univariate analysis and multivariate logistic regression analysis. Results Out of 147 patients included in the study, 51 (34.69%) developed microischemia while the remaining 96 (65.31%) did not experience this condition. Analysis revealed that factors such as sex, age, history of underlying diseases (hypertension, diabetes mellitus), aneurysmal site characteristics, the presence or absence of stenosis in the aneurysm-bearing artery, modified Fisher score at admission, Barthel’s index at discharge, immunoinflammatory index at 3 days postoperatively and at the 6-month follow-up, the presence or absence of aneurysmal wall enhancement, and the presence or absence of aneurysmal lumen showed no statistically significant differences between the two groups (all P > 0.05). By contrast, variables like in operative time, rupture status of the aneurysm before surgery according to World Federation of Neurologic Surgeons (WFNS) grade, aneurysm size, number of stents used, number of guidewires and catheters used, and Evans index between the two groups were found to have statistically significant disparities between those who developed microischemia and those who did not (P 0.3, and the quantity of stents were independent risk factors for the occurrence of ultra-long-term microischemia after aneurysm embolization and provided good predictive performance. Cognitive dysfunction was closely associated with microischemia, with its severity increasing with an increase in the number of ischemic foci.

Paradoxical insomnia (Para-I), also known as pseudoinsomnia or sleep state misperception, is a condition in which the patient complains of severe insomnia but has no objective evidence of sleep disorder, and daytime functioning may be disrupted disproportionately to the degree of patient-reported sleep loss. Para-I is characterized by overestimation of sleep latency (SL) and underestimation of total sleep time (TST). Incorrect assessment of sleep quality hinders the diagnosis, evaluation of severity, and assessment of clinical efficacy of sleep disorders. The pathogenesis of Para-I remains unclear, but may be related to factors such as depression, anxiety, personality traits, social relationships and specific changes in brain structure and function. Studies on the polysomnography (PSG) of the patients with insomnia have found that changes in non-rapid eye movement (NREM) and rapid eye movement (REM) sleep may be related to the degree of subjective-objective sleep discrepancy. PSG is a valuable diagnostic tool for sleep disorders. It allows for the analysis of sleep structure and related physiological and behavioral changes by monitoring various parameters, including electroencephalogram (EEG), electromyogram (EMG), electrooculogram (EOG), oro-nasal airflow, thoracic and abdominal respiratory motions, oxygen saturation, electrocardiogram (ECG) and snoring. In recent years, studies have increasingly explored the sleep EEG and treatment of Para-I with PSG, resulting in significant progress. This article reviews the latest advances in the electroencephalographic characteristics and treatment of Para-I, providing new ideas for precise treatment.

Abstract Breast cancer metastasis to the brain is a clinical challenge rising in prevalence. However, the underlying mechanisms, especially how cancer cells adapt a distant brain niche to facilitate colonization, remain poorly understood. A unique metabolic feature of the brain is the coupling between neurons and astrocytes through glutamate, glutamine, and lactate. Here we show that extracellular vesicles from breast cancer cells with a high potential to develop brain metastases carry high levels of miR-199b-5p, which shows higher levels in the blood of breast cancer patients with brain metastases comparing to those with metastatic cancer in other organs. miR-199b-5p targets solute carrier transporters (SLC1A2/EAAT2 in astrocytes and SLC38A2/SNAT2 and SLC16A7/MCT2 in neurons) to hijack the neuron–astrocyte metabolic coupling, leading to extracellular retention of these metabolites and promoting cancer cell growth. Our findings reveal a mechanism through which cancer cells of a non-brain origin reprogram neural metabolism to fuel brain metastases.