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Abstract Synthetic biology (SynBio) is an interdisciplinary field that includes biology, genomics, engineering, and informatics. The introduction of machine learning technology reduces the requirement for human participation in SynBio research, which may lead to increased biosafety and biosecurity concerns within the complex human–technology-management system in SynBio laboratories compared with traditional biology. The rapid development of SynBio and machine learning technology has added to the systemic complexity of management and technology subsystems, the risks of which remain unclear. To fully understand and address these risks, there is an urgent need to develop a quantitative model. In this study, three-round Delphi interviews were conducted with SynBio experts who have published articles in top journals (e.g., Nature, Science, Cell, etc.) and applied the system dynamics method to build a quantitative analysis model. The model explores the potential risk factors and their complex relationships in the SynBio research. We analyzed three subsystems (biotechnology, information technology, and management), identifying seven key risk factors. Among these, the Average Experience of Newcomers and Tolerable Error Frequency play an essential role in laboratory management. Notably, the biosafety atmosphere has the greatest impact on reducing error rate and increasing safety awareness, as well as on the infrastructure safety of SynBio laboratory. In addition, we also consider the impact of the progressiveness of machine learning in the SynBio research and find that using more advanced machine learning technology leads to lower instrument safety. This study provides a framework for quantifying potential risk factors in SynBio research and lays a theoretical foundation for future laboratory safety management and the development of a global code of conduct for interdisciplinary scientists.

Abstract Choroidal vascularity index (CVI) is an image-based metric applied to assess the choroid in disease but poorly explored in natural aging. In this retrospective cohort study, we assessed a single eye of 309 healthy individuals from 20 to 70 + years, and quantified spatial topography of total choroidal area (TCA), luminal area (LA), stromal area (SA) and CVI (LA: TCA) in cluster and standard retinal templates using a semi-automated approach. CVI was found to be greatest in the central vs. periphery (CVIcentral 67.08% [66.85–67.73] vs. CVIperiphery65.68% [65.32–66.01], p

Abstract The drilling rate index (DRI) of rocks is important for optimizing drilling operations, as it informs the choice of appropriate methods and equipment, ultimately improving the efficiency of rock excavation projects. This study presents a hybrid machine learning approach to predict the DRI of rocks accurately. By integrating grey wolf optimization with support vector machine (GWO-SVM), random forest (GWO-RF), and extreme gradient boosting (GWO-XGBoost) models, the aim was to enhance predictive accuracy. Among these, the GWO-XGBoost model exhibited superior predictive performance, achieving a coefficient of determination (R²) of 0.999, mean absolute error (MAE) of 0.00043, root mean square error (RMSE) of 1.98017, and severity index (SI) of 0.0350 during training. Testing results confirmed its accuracy with R² of 0.999, MAE of 0.00038, RMSE of 1.80790, and SI of 0.0312. Furthermore, the GWO-XGBoost model outperformed the other models in terms of precision, recall, f1-score, and multi-class confusion matrix results for each DRI class. The GWO-RF model also demonstrated high accuracy, ranking second, while the GWO-SVM model showed comparatively lower performance. This research aims to advance rock excavation practices by providing a highly accurate and reliable tool for DRI prediction. The results highlight the significant potential of the GWO-XGBoost model in improving DRI predictions, offering valuable intuitions and practical applications in the field.

Verticillium dahliae causes significant losses in cotton production. To reveal the mechanism of the defense response to V. dahliae in cotton, transcriptomic analyses were performed using cotton cultivars M138 (V. dahliae-resistant) and P2 (V. dahliae-susceptible). The results revealed 11,076 and 6,640 differentially expressed genes (DEGs) in response to V. dahliae, respectively. The weighted gene co-expression network analysis of 4,633 transcription factors (TFs) indicated a “MEblue” module containing 654 TFs that strongly correlate with resistance to V. dahliae. Among these TFs, the ethylene response factor Ghi_A05G10166 (GhERF91) was identified as a putative hub gene with a defense response against V. dahliae. A virus-induced gene silencing assay and exogenous application of ethephon showed that GhERF91 is activated by ethylene and positively regulates the response to V. dahliae exposure in cotton. This study provides fundamental transcriptome data and a putative causal gene (GhERF91) associated with resistance to V. dahliae, as well as genetic resources for breeding V. dahliae-resistant cotton.

Abstract Rheumatoid arthritis (RA) is a debilitating autoimmune disease characterized by chronic joint inflammation and cartilage damage. Current therapeutic strategies often result in side effects, necessitating the development of targeted and safer treatment options. This study introduces a novel nanotherapeutic system, 2-APB@DGP-MM, which utilizes macrophage membrane (MM)-encapsulated nanoparticles (NPs) for the targeted delivery of 2-Aminoethyl diphenylborinate (2-APB) to inflamed joints more effectively. The NPs are designed with a matrix metalloproteinase (MMP)-cleavable peptide, allowing for MMP-responsive drug release within RA microenvironment. Comprehensive in vitro and in vivo assays confirmed the successful synthesis and loading of 2-APB into the DSPE-GPLGVRGC-PEG (DGP) NPs, as well as their ability to repolarize macrophages from a pro-inflammatory M1 to an anti-inflammatory M2 phenotype. The NPs demonstrated high biocompatibility, low cytotoxicity, and enhanced cellular uptake. In a collagen-induced arthritis (CIA) mouse model, intra-articular injection of 2-APB@DGP-MM significantly reduced synovial inflammation and cartilage destruction. Histological analysis corroborated these findings, demonstrating marked improvements in joint structure and delayed disease progression. Above all, the 2-APB@DGP-MM nanotherapeutic system offers a promising and safe approach for RA treatment by modulating macrophage polarization and delivering effective agents to inflamed joints. Graphical Abstract

[Introduction] This paper aims to deeply analyze and improve China's carbon pricing mechanism to more effectively promote the social transition to green and low-carbon, and at the same time enhance China's leadership and initiative in the process of global carbon peaking and carbon neutrality. [Method] By comprehensively sorting out the current situation and future trends of the global carbon pricing mechanism, this article deeply analyzed the shortcomings of China's existing carbon pricing mechanism, such as insufficient correlation with the overall climate policy goals, unclear nature of property rights in the carbon market, and inactive market entities. This paper further discussed the potential impact of rising carbon price on China's emission reduction effect and energy supply guarantee. [Result] Based on China's national conditions, this paper gives the strategic direction and corresponding measures to construct China's carbon pricing mechanism by using carbon market carbon quota, carbon tax, coordination between carbon market and carbon tax, and carbon finance. [Conclusion] On the basis of clarifying the development ideas of China's carbon pricing mechanism, it provides a countermeasure reference for China to win more voice in the international carbon pricing mechanism, such as strategies for synergizing the domestic electricity certificate and carbon markets, improving the "integrity" of China's green certificates, engaging in the promotion of mutual recognition in international carbon markets, and collaborating to establish coordinated carbon pricing mechanisms among nations.

Abstract The lower respiratory tract (LRT) microbiome impacts human health, especially among critically ill patients. However, comprehensive characterizations of the LRT microbiome remain challenging due to low microbial mass and host contamination. We develop a chelex100-based low-biomass microbial-enrichment method (CMEM) that enables deep metagenomic profiling of LRT samples to recover near-complete microbial genomes. We apply the method to 453 longitudinal LRT samples from 157 intensive care unit (ICU) patients in three geographically distant hospitals. We recover 120 high-quality metagenome-assembled genomes (MAGs) and associated plasmids without culturing. We detect divergent longitudinal microbiome dynamics and hospital-specific dominant opportunistic pathogens and resistomes in pneumonia patients. Diagnosed pneumonia and the ICU stay duration were associated with the abundance of specific antibiotic-resistance genes (ARGs). Moreover, CMEM can serve as a robust tool for genome-resolved analyses. MAG-based analyses reveal strain-specific resistome and virulome among opportunistic pathogen strains. Evolutionary analyses discover increased mobilome in prevailing opportunistic pathogens, highly conserved plasmids, and new recombination hotspots associated with conjugative elements and prophages. Integrative analysis with epidemiological data reveals frequent putative inter-patient strain transmissions in ICUs. In summary, we present a genome-resolved functional, transmission, and evolutionary landscape of the LRT microbiota in critically ill patients.

Abstract Background Postoperative cognitive dysfunction (POCD) is common following surgery in elderly patients. The role of the preoperative gut microbiota in POCD has attracted increasing attention, but the potential underlying mechanisms remain unclear. This research aimed to investigate the impact of the preoperative gut microbiota on POCD. Methods Herein, we analyzed the preoperative gut microbiota of POCD patients through a prospective specimen collection and retrospective blinded evaluation study. Then, we transferred the preoperative gut microbiota of POCD patients to antibiotic-treated rats and established POCD model by abdominal surgery to explore the impact of the preoperative gut microbiota on pre- and postoperative cognitive function and systemic inflammation. The gut microbiota was analyzed using 16S rRNA sequencing analysis. The Morris water maze test was performed to evaluate learning and memory abilities. The inflammatory cytokines TNF-α, IL-1β and IL-6 in the serum and hippocampus were measured by ELISA. Microglia were examined by immunofluorescence staining for Iba-1. Results Based on the decrease in the postoperative MMSE score, 24 patients were identified as having POCD and were matched with 24 control patients. Compared with control patients, POCD patients exhibited higher BMI and lower preoperative MMSE score. The preoperative gut microbiota of POCD patients had lower bacterial richness but a larger distribution, decreased abundance of Firmicutes and increased abundance of Proteobacteria than did that of control patients. Compared with rats that received preoperative fecal samples of control patients, rats that received preoperative fecal samples of POCD patients presented an increased abundance of Desulfobacterota, decreased cognitive function, increased levels of TNF-α and IL-1β in the serum, increased levels of TNF-α and greater microglial activation in the hippocampus. Additionally, correlation analysis revealed a positive association between the abundance of Desulfobacterota and the level of serum TNF-α in rats. Then, we performed abdominal surgery to investigate the impact of the preoperative gut microbiota on postoperative conditions, and the surgery did indeed cause POCD and inflammatory response. Notably, compared with rats that received preoperative fecal samples of control patients, rats that received preoperative fecal samples of POCD patients displayed exacerbated cognitive impairment; increased levels of TNF-α, IL-1β and IL-6 in the serum and hippocampus; and increased activation of microglia in the hippocampus. Conclusions Our findings suggest that the preoperative gut microbiota of POCD patients can induce preoperative and aggravate postoperative cognitive impairment and systemic inflammation in rats. Modulating inflammation by targeting the gut microbiota might be a promising approach for preventing POCD.

Background: The senescence of endothelial cells is of great importance involving in atherosclerosis (AS) development. Recent studies have proved the protective role of mesenchymal stem cell-derived extracellular vesicles in AS, herein, we further desired to unvei their potential regulatory mechanisms in endothelial cell senescence. Methods: Senescence induced by H2O2 in primary mouse aortic endothelial cells (MAECs) was evaluated by SA-β-gal staining. Targeted molecule expression was detected by qRT-PCR and Western blotting. The biological functions of MAECs were determined by CCK-8, flow cytometry, transwell, and tube formation assays. Oxidative injury was assessed by LDH, total and lipid ROS, LPO and MDA levels. The proliferation of adipose-derived mesenchymal stem cell (ADSCs) was analyzed by EdU assay. Effect of ADSCs-derived extracellular vesicles (ADSC-EVs) on AS was investigated in HFD-fed ApoE−/− mice. Results: miR-674-5p was up-regulated, while C1q/TNF-related protein 9 (CTRP9) was down-regulated in H2O2-induced senescent MAECs. CTRP9 was demonstrated as a target gene of miR-674-5p. miR-674-5p inhibition restrained senescence, oxidative stress, promoted proliferation, migration, and angiogenesis of H2O2-stimulated MAECs via enhancing CTRP9 expression. Moreover, treatment with ADSC-EVs inhibited H2O2-induced senescence and dysfunction of MAECs through regulating miR-674-5p/CTRP9 axis. In the in vivo AS mouse model, ADSC-EVs combination with miR-674-5p silencing slowed down AS progression via up-regulation of CTRP9. Conclusion: ADSC-EVs repressed endothelial cell senescence and improved dysfunction via promotion of CTRP9 expression upon miR-674-5p deficiency during AS progression, which might provide vital evidence for ADSC-EVs as a promising therapy for AS.

Incorporating the self-regulatory mechanism with time delay to a plant-sulfide feedback system for intertidal salt marshes, we proposed and studied a functional reaction-diffusion model. We analyzed the stability of the positive steady state of the system, and derived the sufficient conditions for the occurrence of Hopf bifurcations. By deriving the normal form on the center manifold, we obtained the formulas determining the properties of the Hopf bifurcations. Our analysis showed that there is a critical value of time delay. When the time delay is greater than the critical value, the system will show asymptotical temporal periodic patterns while the system will display asymptotical spatial homogeneous patterns when the time delay is smaller than the critical value. Our numerical study showed that there are transient fairy circles for any time delay while there are different types of fairy circles and rings in the system. Our results enhance the concept that transient fairy circle patterns in intertidal salt marshes can infer the underlying ecological mechanisms and provide a measure of ecological resilience when the self-regulatory mechanism with time delay is considered.

Background: Benign prostate hyperplasia (BPH) occurs in elder men globally with high prevalence. Human diet and lifestyle aroused great attention in the prevalence of BPH. Prostate enlargement (PE) is a major symptom of BPH. Objectives: To elaborate the effect of total diet quality for adults from the United States, we investigated the association between Health Eating Index (HEI)-2015 and the risk of PE in adults from the National Health and Nutrition Examination Survey (NHANES). Methods: This cross-sectional study was conducted based on NHANES 2001–2008. Participants who reported a PE history were included. We conducted a logistic regression analysis to investigate the association between HEI-2015 and PE. Results: A total of 4,866 male participants aged 40 and above were enrolled. Compared with Q1 of HEI-2015, no significant differences were found in adjusted models. Higher vegetables intake (Odds ratio [OR] = 1.073; 95% confidence interval [95%CI] 1.015 to 1.134, P = 0.02) and higher total dairy intake (OR = 1.034; 95%CI 1.009 to 1.061, P = 0.01) were significantly related with higher risk of PE. Conclusions: There was no significant difference between HEI-2015 and PE after full adjustment. Total vegetables and dairy product might be associated with higher risk of PE and needed further validation.

Abstract Intrahepatic cholangiocarcinoma (iCCA) presents a challenging diagnosis due to its nonspecific early clinical manifestations, often resulting in late-stage detection and high mortality. Diagnosing iCCA is further complicated by its limited accuracy, often necessitating multiple invasive procedures for precise identification. Despite carbohydrate antigen 19–9 (CA19-9) having been investigated and employed for iCCA diagnosis, it demonstrates modest diagnostic performance. Consequently, the identification of novel biomarkers with improved sensitivity and specificity remains an imperative yet formidable task. Autoantibodies, as early indicators of the immune response against cancer, offer a promising avenue for enhancing diagnostic accuracy. Our study aimed to identify non-invasive blood-based autoantibody biomarkers capable of distinguishing iCCA patients from healthy individuals (CTRs). We profiled autoantibodies in 26 serum samples (16 iCCAs and 10 CTRs) using protein microarrays containing 1622 functional proteins. Leveraging machine learning techniques, we identified a signature composed of three autoantibody biomarkers (NDE1, PYCR1, and VIM) in conjunction with CA19-9 for iCCA detection. This combined signature demonstrated superior diagnostic performance with an AUC of 96.9%, outperforming CA19-9 alone (AUC: 83.8%). These results suggest the potential of autoantibody biomarkers to develop a complementary non-invasive diagnostic utility for routine iCCA screening.

Abstract Background Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a rare cause of heart attack, which may not receive sufficient attention from patients during post-discharge treatment, especially among those with normal coronary angiography results. Case presentation We present the case of a 65-year-old woman who was readmitted to the hospital with ventricular septal rupture (VSR) complicated by ventricular aneurysm, occurring 2 weeks after myocardial infarction. During the initial admission, coronary angiography revealed normal coronary arteries, leading to a diagnosis of MINOCA. Epicardial coronary vasospasm or coronary embolism was considered as potential causes; however, the patient did not adhere to standardized treatment upon initial discharge. The delayed VSR led to a decline in cardiac function but did not result in severe hemodynamic impairment. Following correction of heart failure with medications, the patient underwent percutaneous VSR repair 19 days after diagnosis and was discharged with a favorable recovery. Conclusions The occurrence of delayed VSR complicated with ventricular aneurysm in patients with MINOCA is rare, highlighting the possibility of serious complications in MINOCA cases. Both cardioprotective therapies and cause-targeted therapies are essential in the management of patients with MINOCA.

In order to improve the yield of jackfruit peel pectin (JFPP) and obtain high-purity pectin with good functional properties, this study optimized the extraction process of pectin by ultrasound-assisted cellulase enzyme method through response surface experiments. The extracted pectin was preliminarily purified, including degreasing, deproteinization, decolorization, and dialysis concentration process. The purified pectin was then enzymatically esterified and modified by de-esterification to obtain de-esterified jackfruit peel pectin (DE-JFPP), and a comparative analysis was conducted on the basic composition, molecular weight, monosaccharide composition, functional group characteristics, thermal stability, and microstructure of the pectin before and after modification. The results showed that the optimal conditions for the extraction process were enzyme dosage of 0.7%, the enzymatic hydrolysis temperature of 30.4 ℃, and the pH of 4.6. It was observed that the yield of JFPP was 15.26%±0.07% under the specified conditions. The galacturonic acid content in the modified pectin increased from 79.10% to 83.24%, with a decrease in total sugar content from 43.42% to 41.90%, a decrease in esterification degree from 84.25% to 32.36%, and a decrease in weight-average molecular weight from 29.24 ku to 28.49 ku. Both JFPP and DE-JFPP contained eleven monosaccharides and belonged to the RG-I pectin with a decrease in the degree of branching in DE-JFPP. Fourier transform infrared (FTIR) spectroscopy demonstrated that both the pectin before and after modification had characteristic absorption peaks of pectin, and the peak area corresponding to the esterified carboxyl acid group decreased after modification. The JFPP and DE-JFPP demonstrated high thermal stability, with solubilization temperatures of 160.22 ℃ and 123.28 ℃, and degradation temperatures of 255.11 ℃ and 230.56 ℃, respectively. Scanning electron micrographs (SEM) showed that JFPP had a smooth surface and a compact structure, and DE-JFPP had a rough surface and a loose structure. This study optimized the extraction process of jackfruit peel pectin, improving its yield. Results demonstrated that the esterified pectin had favorable physicochemical properties and microstructure, meeting requirements for gel carrier systems in various fields and expanding the utilization space of jackfruit peel pectin.

Abstract Objective To test the glycemic susceptibility in three urological cancers and eight urological/reproductive diseases using the Mendelian randomization (MR) method. Materials and methods Two-sample MR was applied to investigate the causal role of three glycemic traits (type II diabetes, fasting glucose and glycated hemoglobin (HbA1c)) in eleven urological/reproductive diseases (kidney cancer, bladder cancer, prostate cancer, kidney/ureter stone, urinary incontinence, benign prostatic hyperplasia, erectile dysfunction, female infertility, male infertility, abnormal spermatozoa and polycystic ovary syndrome). Further multivariate MR (MVMR) and mediating analysis were performed to investigate the associations. Results Among all the 11 diseases, type II diabetes was positively associated with erectile dysfunction, which was stable across both cohorts [odds ratio (OR): 1.59, 95% confidence interval (CI): 1.15–2.20, P = 0.005 for FinnGen Biobank and OR: 1.14, 95% CI: 1.08–1.21, P

Abstract Immunotherapy exhibits considerable promise for sustained tumor reduction. However, current cancer immunotherapy methods elicit limited responses due to the inadequate immunogenicity exhibited by cancer cells. This obstacle may be addressed using nanoplatforms that can activate synergistic therapies (photodynamic therapy and ferroptosis) in response to the acidic pH of the tumor microenvironment. We previously developed an amphiphilic photosensitizer, SR780, which displays satisfactory photodynamic effects. This photosensitizer is inactivated when bound to Fe3+ (SR780Fe) but is activated upon release in mildly acidic conditions. In this study, M1 macrophage-derived extracellular vesicles (EVs) were fused with REV and SR780Fe–loaded liposomes (REV@SR780Fe@Lip) to form REV@SR780Fe@LEV hybrid nanovesicles. Further modification with the RS17 peptide for tumor targeting enabled a combination of photodynamic therapy, ferroptosis, and cGAS-STING pathway activation, resulting in enhanced antitumor efficacy through a synergistic effect. Upon laser irradiation, REV@SR780Fe@LEV-RS17 demonstrated antitumor effects in 4T1 breast cancer models, including the inhibition of lung and liver metastasis, as well as prevention of tumor recurrence. Graphical Abstract

Abstract Objective Postoperative cognitive dysfunction (POCD) is a serious surgical complication. We assessed the different POCD incidences between anesthesia using sevoflurane and sevoflurane combined with dexmedetomidine, with propofol-based sedation in elderly patients who underwent a thoracic surgical procedure. Methods A total of 90 patients aged 65 to 80 years old who underwent a thoracic surgical procedure at our hospital and 15 nonsurgical participants as controls, were enrolled in this study. Patients were divided in a randomized 1:1:1 ratio into 3 groups. All participants were randomized into a trial with three anesthesia groups (P, PS, PSD) or a control group (C) of healthy matches. All trial groups received distinct anesthetic combinations during surgery, while controls mirrored patient criteria.Group P (propofol and remifentanil were maintained during the surgery), Group PS (propofol, remifentanil, and sevoflurane were maintained during the surgery), and Group PSD (propofol, remifentanil, sevoflurane, and dexmedetomidine were maintained during the surgery).All participants were rated using a series of cognitive assessment scales before and three days after surgery. All participants were interviewed over the telephone, 7 days, 30 days, and 90 days postoperatively. Results POCD incidences in the PSD (combined anesthetization with propofol, sevoflurane, and dexmedetomidine) group was significantly lower than that in the PS (combined anesthetization with propofol and sevoflurane) group, 1 day post-surgery (10.0% vs. 40.0%, P = 0.008), and the results were consistent at 3 days post-surgery. When the patients were assessed 7 days, 30 days, and 90 days postoperatively, there was no significant difference in POCD incidence among the three groups. Multivariate logistic regression analysis of POCD one day after surgery showed that education level was negatively correlated with incidence of POCD (P = 0.018) and single lung ventilation time was positively correlated with incidence of POCD (P = 0.001). Conclusion For elderly patients who underwent a thoracic surgical procedure, dexmedetomidine sedation shows an obvious advantage on improving short-term POCD incidence, which is caused by sevoflurane.

In order to explore the quality characteristics of fermented kiwifruit black tea wine, kiwifruit and black tea were fermented, and the flavor and quality of fermented kiwifruit black tea wine were comprehensively analyzed by using high performance liquid chromatography, headspace solid-phase microextraction-gas chromatography-mass spectrometry and electronic nose technology, combined with sensory evaluation methods, through organic acid content, monomeric phenol content, amino acid content, volatile substances and sensory characteristics. The results showed that the types and contents of monomeric phenols and volatile substances in kiwifruit tea juice were significantly increased by fermentation (P

Abstract Objective This cross‐sectional study aimed to determine the epidemiology of olfactory and gustatory dysfunctions related to COVID‐19 in China. Methods This study was conducted by 45 tertiary Grade‐A hospitals in China. Online and offline questionnaire data were obtained from patients infected with COVID‐19 between December 28, 2022, and February 21, 2023. The collected information included basic demographics, medical history, smoking and drinking history, vaccination history, changes in olfactory and gustatory functions before and after infection, and other postinfection symptoms, as well as the duration and improvement status of olfactory and gustatory disorders. Results Complete questionnaires were obtained from 35,566 subjects. The overall incidence of olfactory and taste dysfunction was 67.75%. Being female or being a cigarette smoker increased the likelihood of developing olfactory and taste dysfunction. Having received four doses of the vaccine or having good oral health or being a alcohol drinker decreased the risk of such dysfunction. Before infection, the average olfactory and taste VAS scores were 8.41 and 8.51, respectively; after infection, they decreased to 3.69 and 4.29 and recovered to 5.83 and 6.55 by the time of the survey. The median duration of dysosmia and dysgeusia was 15 and 12 days, respectively, with 0.5% of patients having symptoms lasting for more than 28 days. The overall self‐reported improvement rate was 59.16%. Recovery was higher in males, never smokers, those who received two or three vaccine doses, and those that had never experienced dental health issues, or chronic accompanying symptoms. Conclusions The incidence of dysosmia and dysgeusia following infection with the SARS‐CoV‐2 virus is high in China. Incidence and prognosis are influenced by several factors, including sex, SARS‐CoV‐2 vaccination, history of head‐facial trauma, nasal and oral health status, smoking and drinking history, and the persistence of accompanying symptoms.

Summary: In situ liquid-phase electrochemical transmission electron microscopy (ec-TEM) as a valuable technique has been widely used in studying metal deposition in battery materials. While real-time observations of metallic nucleation, growth, and dendrite formation using microscale ec-TEM liquid cells are investigated, existing cells exhibit nonuniform electric field distribution along electrodes, limiting measurement reliability and quantitative analysis. Here, we introduce an advanced electrode design for ec-TEM chips, ensuring a uniform electric field for precise characterization of early-stage metal deposition closer to practical battery conditions. Both simulation and experimental investigations demonstrate that these specially designed ec-TEM chips facilitate quantitative electrochemical characterization combined with the in situ TEM technique in comparison with commercially available chips. We thus provide a significant progression toward optimizing the performance and reliability of quantitative in situ liquid-phase TEM measurements, essential for understanding and improving electrochemical systems.

Background The planting of mangroves is extensively used to control the invasive plant Spartina alterniflora in coastal wetlands. Different plant species release diverse sets of small organic compounds that affect rhizosphere conditions and support high levels of microbial activity. The root-associated microbial community is crucial for plant health and soil nutrient cycling, and for maintaining the stability of the wetland ecosystem. Methods High-throughput sequencing was used to assess the structure and function of the soil bacterial communities in mudflat soil and in the rhizosphere soils of S. alterniflora, mangroves, and native plants in the Oujiang estuarine wetland, China. A distance-based redundancy analysis (based on Bray–Curtis metrics) was used to identify key soil factors driving bacterial community structure. Results S. alterniflora invasion and subsequent mangrove afforestation led to the formation of distinct bacterial communities. The main soil factors driving the structure of bacterial communities were electrical conductivity (EC), available potassium (AK), available phosphorus (AP), and organic matter (OM). S. alterniflora obviously increased EC, OM, available nitrogen (AN), and NO3−-N contents, and consequently attracted copiotrophic Bacteroidates to conduct invasion in the coastal areas. Mangroves, especially Kandelia obovata, were suitable pioneer species for restoration and recruited beneficial Desulfobacterota and Bacilli to the rhizosphere. These conditions ultimately increased the contents of AP, available sulfur (AS), and AN in soil. The native plant species Carex scabrifolia and Suaeda glauca affected coastal saline soil primarily by decreasing the EC, rather than by increasing nutrient contents. The predicted functions of bacterial communities in rhizosphere soils were related to active catabolism, whereas those of the bacterial community in mudflat soil were related to synthesis and resistance to environmental factors. Conclusions Ecological restoration using K. obovata has effectively improved a degraded coastal wetland mainly through increasing phosphorus availability and promoting the succession of the microbial community.

BackgroundEndometriosis is a multifaceted disorder with genetic, immune, inflammatory, and multifactorial origins. Vitamin B6 serves as a pivotal coenzyme in various metabolic pathways involving lipids, hemes, nucleic acids, proteins, and carbohydrates. Dysregulation or deficiency of vitamin B6 can perturb human physiology. However, the relationship between dietary vitamin B6 and endometriosis remains elusive. This study aims to explore how dietary intake of vitamin B6 is associated with the risk of endometriosis.MethodsUsing cross-sectional data from the National Health and Nutrition Examination Survey, we analyzed information from American women aged 20–54 years between 1999 and 2006. After adjusting for relevant covariates, multivariable logistic regression analysis was employed to evaluate correlations.ResultsA total of 4,453 women were included in the study. The multiple linear regression model revealed a positive association between dietary vitamin B6 intake and the risk of endometriosis, even after controlling for confounding variables. Compared to individuals with lower vitamin B6 consumption (Q1: 1.90 mg/day) were 1.22 (95% CI: 0.88–1.69, p = 0.23), 1.22 (95% CI: 0.86–1.73, p = 0. 279), and 1.51 (95% CI, 1.01–2. 24, p = 0.04), respectively.ConclusionOur findings suggest a positive correlation between endometriosis and dietary vitamin B6 intake. Further investigations are imperative to establish a causal relationship between dietary vitamin B6 intake and endometriosis.

Dendrobium is a precious Chinese herbal medicine, which belongs to the genus Orchidaceae. Ancient records and modern pharmacological research show that Dendrobium has pharmacological effects such as anti-tumor, antioxidant regulating immunity and blood glucose, and anti-aging. Dendrobium contains polysaccharides, alkaloids, bibenzyl, sesquiterpenes, phenanthrene, polyphenols and other types of chemicals. Its pharmacological activity is closely related to these chemical components. For example, dendrobium extracts can achieve anti-tumor effects by inhibiting tumor cell proliferation and metastasis, promoting cell apoptosis and ferroptosis, or increasing cell sensitivity to chemotherapy drugs. It enhances immunity by regulating immune cell activity or cytokine release. In addition, it can alleviate neurodegenerative diseases by protecting nerve cells from apoptotic damage. In recent years, research reports on biologically active compounds in Dendrobium have shown a blowout growth, which makes us realize that it is meaningful to continuously update the research progress on the components and pharmacological regulatory mechanism of this traditional Chinese medicine. By classifying the collected chemical components according to different chemical structures and summarizing their pharmacological mechanisms, we investigated the current research progress of Dendrobium and provide a more comprehensive scientific foundation for the further development and clinical transformation of Dendrobium in the future.

This study assesses the capabilities of OpenAI’s ChatGPT-4 and ChatGPT-4o in solving mathematics problems from the National Assessment of Educational Progress (NAEP) across grades 4, 8, and 12. Results indicate that ChatGPT-4o slightly outperform ChatGPT-4 and both models generally surpass U.S. students’ performance across all grades, content areas, item type, and difficulty level. However, both models perform worse on geometry and measurement than on algebra and face more difficulties with high-difficulty mathematics items. This investigation highlights the strengths and limitations of AI as a supplementary educational tool, pinpointing areas for improvement in spatial intelligence and complex mathematical problem-solving. These findings suggest that while AI has the potential to support instruction in specific mathematical areas like algebra, there remains a need for careful integration and teacher-mediated strategies in areas where AI is less effective.

Background: Allergic rhinitis (AR) is a global health issue affecting millions of individuals worldwide. Pyroptosis has emerged as a major player in the development of AR, and targeting its inhibition with specific drugs holds promise for AR treatment. However, a comprehensive understanding of the precise mechanisms underlying pyroptosis in AR remains to be explored, warranting further investigation. Objective: This study aims to elucidate the roles of HMGB1, Sphk1, and HDAC4 in regulating human nasal epithelial cell (hNEC) pyroptosis and AR. Methods: An in vitro AR cell culture model and an in vivo AR mouse model were established. Western blot, ELISA, histological staining, and flow cytometry were utilized to confirm the gene and protein expression. The interactions among Sphk1, HDAC4, and HMGB1 were validated through ChIP, Co-IP, and Dual-luciferase assay. Results and conclusion: We identified that the expression levels of Sphk1, HMGB1, and inflammasome components, including IL-18, and IL-1β were elevated in AR patients and mouse models. Knockdown of Sphk1 inhibited hNEC pyroptosis induced by dust mite allergen. Overexpression of HDAC4 suppressed HMGB1-mediated pyroptosis in hNECs. In addition, HDAC4 was found to mediate the transcriptional regulation of HMGB1 via MEF2C, a transcription factor. Additionally, Sphk1 was shown to interact with CaMKII-δ, promoting the phosphorylation of HDAC4 and inhibiting its cytoplasmic translocation. Knockdown of HDAC4 reversed the effect of Sphk1 knockdown on pyroptosis. These discoveries offer a glimpse into the molecular mechanisms underlying AR and suggest potential therapeutic targets for the treatment of this condition.

Summary: Obesity and fatty liver diseases—metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH)—affect over one-third of the global population and are exacerbated in individuals with reduced functional aldehyde dehydrogenase 2 (ALDH2), observed in approximately 560 million people. Current treatment to prevent disease progression to cancer remains inadequate, requiring innovative approaches. We observe that Aldh2−/− and Aldh2−/−Sptbn1+/− mice develop phenotypes of human metabolic syndrome (MetS) and MASH with accumulation of endogenous aldehydes such as 4-hydroxynonenal (4-HNE). Mechanistic studies demonstrate aberrant transforming growth factor β (TGF-β) signaling through 4-HNE modification of the SMAD3 adaptor SPTBN1 (β2-spectrin) to pro-fibrotic and pro-oncogenic phenotypes, which is restored to normal SMAD3 signaling by targeting SPTBN1 with small interfering RNA (siRNA). Significantly, therapeutic inhibition of SPTBN1 blocks MASH and fibrosis in a human model and, additionally, improves glucose handling in Aldh2−/− and Aldh2−/−Sptbn1+/− mice. This study identifies SPTBN1 as a critical regulator of the functional phenotype of toxic aldehyde-induced MASH and a potential therapeutic target.

Background: Sepsis-associated coagulopathy specifically refers to widespread systemic coagulation activation accompanied by a high risk of hemorrhage and organ damage, which in severe cases manifests as disseminated intravascular coagulation (DIC), or even develops into multiple organ dysfunction syndrome (MODS). The complement system and the coagulation system as the main columns of innate immunity and hemostasis, respectively, undergo substantial activation after sepsis. Summary: Dysfunction of the complement, coagulation/fibrinolytic cascades caused by sepsis leads to “thromboinflammation,” which ultimately amplifies the systemic inflammatory response and accelerates the development of MODS. Recent studies have revealed that massive activation of the complement system exacerbates sepsis-induced coagulation and even results in DIC, which suggests that inhibition of complement activation may have therapeutic potential in the treatment of septic coagulopathy. Key Messages: Sepsis-associated thrombosis involves the upregulation or activation of procoagulant factors, down-regulation or inactivation of anticoagulant factors, and impairment of the fibrinolytic mechanism. This review aims to summarize the latest literature and analyze the underlying molecular mechanisms of the activation of the complement system on the abnormal coagulation cascades in sepsis.

Steel containers used for geological disposal of high-level radioactive waste will be gradually thinned or even perforated due to corrosion, which will lead to radiolysis of nuclides when they contact with infiltrated groundwater and produce H2O2. This work focused on investigating the influence of H2O2 concentration (0%, 0.001%, 0.01%, 0.1% and 1% by volume) on the corrosion behavior of NiCu low alloy steel as the candidate material for containers was comparatively studied by combining corrosion weight loss test, corrosion product analysis, morphology characterization, thermodynamic analysis and electrochemical measurements. As [H2O2] = 0.001%, H2O2 inhibited the formation of γ-FeOOH and enhanced the compactness of rust layer, which effectively blocked the migration of aggressive ions and slowed down the cathodic reduction reaction of rust, thus improving the corrosion resistance of NiCu steel. With the increase of [H2O2] (0.01%→1%), the cathodic process of NiCu steel corrosion was promoted by the increase of dissolved oxygen involved in cathodic depolarization. Meanwhile, the relative content of Fe3O4 in the rust increased, while Fe6(OH)12SO4 and Fe6(OH)12CO3 decreased obviously, which led to the loose and porous rust layer, thus accelerating the corrosion of NiCu steel.

Abstract The aim of this study is to assess the relationship between dietary intake of fatty acids and the age-related macular degeneration (AMD) in the United States population. Adult participants of the 2005–2008 National Health and Nutrition Examination Survey (NHANES) were included in this nationwide cross-sectional study. Dietary fatty acid intake was obtained from two 24-h dietary recall interviews. The intake of dietary fatty acids was analyzed as a continuous and categorical variable. AMD status was assessed using nonmydriatic fundus photographs. Univariate and multivariate logistic regression analyses were used to assess the association between dietary fatty acid intake and AMD. The unweighted population included 4702 individuals of whom 374 had AMD. After adjusting for relevant variables, each 1 unit increase (1 mg/1000 kcal) intake of EPA (OR: 0.996, 95% CI: 0.993–0.996, P = 0.018), DPA (OR: 0.976, 95% CI: 0.962–0.990, P = 0.002), and DHA (OR: 0.996, 95% CI: 0.994–0.999, P = 0.003) were significantly decreased odds of any AMD. The highest versus lowest quartile of EPA (OR: 0.476, P for trend

Abstract Background Both the triglyceride-glucose (TyG) index, as a surrogate marker of insulin resistance, and systemic inflammation are predictors of cardiovascular diseases; however, little is known about the coexposures and relative contributions of TyG index and inflammation to cardiovascular diseases. Using the nationally representative data from the China Health and Retirement Longitudinal Study (CHARLS), we conducted longitudinal analyses to evaluate the joint and mutual associations of the TyG index and high-sensitivity C-reactive protein (hsCRP) with cardiovascular events in middle-aged and older Chinese population. Methods This study comprised 8 658 participants aged at least 45 years from the CHARLS 2011 who are free of cardiovascular diseases at baseline. The TyG index was calculated as Ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. Cardiovascular events were defined as the presence of physician-diagnosed heart disease and/or stroke followed until 2018.We performed adjusted Cox proportional hazards regression and mediation analyses. Results The mean age of the participants was 58.6 ± 9.0 years, and 3988 (46.1%) were females. During a maximum follow-up of 7.0 years, 2606 (30.1%) people developed cardiovascular diseases, including 2012 (23.2%) cases of heart diseases and 848 (9.8%) cases of stroke. Compared with people with a lower TyG index (

Abstract Polymer flooding has proved an effective technique to improve development efficiency in heterogeneous reservoirs. Previously, operators usually employed continuous injection of large polymer slugs. However, problems existed including premature injection profile reversal during development, ineffective circulation of polymer solution in low-permeability zones, and excessive polymer consumption in the late development stage. The paper proposed a combination method, named as polymer-alternating-water (PAW), to solve the issues of traditional polymer flooding. The characteristic of this method is injecting water slugs between polymer slugs during the polymer flooding process. At present, research on the PAW technique is limited, with the operational parameters, oil recovery mechanisms, and applicability under various reservoir conditions remaining unclear. In this work, a numerical polymer flooding model is developed using the commercial CMG-STARS reservoir simulation module to investigate the oil displacement performance of PAW. Numerical simulations are performed to determine the optimal parameters for maximizing oil recovery factor. The results indicated compared with continuous polymer flooding, PAW shows multiple peaks in daily oil production rate, with a significantly decreased decline rate, resulting in a 1.47% increase in recovery factor. Under different reservoir conditions including mean permeability, heterogeneity, and crude oil viscosity, PAW can achieve further improvements on the basis of continuous polymer flooding. Polymer adsorption and injection concentration significantly impact the recovery factor, requiring further optimization for field applications. In this study, better polymer flooding performance was achieved when the number of alternating cycles of PAW was 2, and the injected alternating water slug volume was 50%. This study contributes to a deeper understanding of the key mechanisms and parameters in PAW enhanced oil recovery process, thereby providing guidance for the further optimization and field application of this technique.

Mg-based hydrides are too stable and the kinetics of hydrogen absorption and desorption is not satisfactory. An efficient way to improve these shortcomings is to employ reactive ball milling to synthesize the nanocomposite materials of Mg and additives. In this experiment, TiF3 was selected as an additive, and the mechanical milling method was employed to prepare the experimental alloys. The alloys used in this experiment were the as-cast Ce5Mg85Ni10, as-milled Ce5Mg85Ni10 and Ce5Mg85Ni10 + 3 wt.% TiF3. The phase transformation, structural evolution, isothermal and non-isothermal hydrogenation and dehydrogenation performances of the alloys were inspected by XRD, SEM, TEM, Sievert apparatus, DSC and TGA. It revealed that nanocrystalline appeared in the as-milled samples. Compared with the as-cast alloy, ball milling made the particle dimension and grain size decrease dramatically and the defect density increase significantly. The addition of TiF3 made the surface of ball milling alloy particles markedly coarser and more irregular. Ball milling and adding TiF3 distinctly improved the activation and kinetics of the alloys. Moreover, ball milling along with TiF3 can decrease the onset dehydrogenation temperature of Mg-based hydrides and slightly ameliorate their thermodynamics.

The uncertainty principle for vector-valued functions of $ L^2({\mathbb{R}}^n, {\mathbb{R}}^m) $ with $ n\ge 2 $ are studied. We provide a stronger uncertainty principle than the existing one in literature when $ m\ge 2 $. The phase and the amplitude derivatives in the sense of the Fourier transform are considered when $ m = 1 $. Based on these definitions, a generalized uncertainty principle is given.

Abstract Clear cell renal cell carcinoma (ccRCC) is a common malignant tumor, and the role of carbohydrate sulfotransferase 11 (CHST11) in this cancer remains unclear. Here, by using bioinformatics methods, we comprehensively analyzed the relationship between CHST11 and clinical significance, immune infiltration, functional enrichment, m6A methylation, and protein–protein interaction networks. We found that CHST11 expression was significantly higher in ccRCC samples than in normal tissues. Additionally, CHST11 levels correlated with the clinicopathological features of ccRCC patients and functioned as a prognostic factor for patient survival. Functional analysis revealed the involvement of CHST11 in metabolic pathways. Immune infiltration and m6A methylation analysis suggested the association of CHST11 with immune cell abundance in the tumor microenvironment and specific methylation patterns in ccRCC. The in vitro analysis of the clinical samples and ccRCC cell lines demonstrated that the overexpression of CHST11 promotes ccRCC cell proliferation, migration, and invasion, while its suppression has the opposite effect. Thus, CHST11 may play a remarkable role in the occurrence and progression of ccRCC. Functionally, CHST11 promotes the aggressiveness of ccRCC cells. These findings provide insights into the role of CHST11 in ccRCC progression. Registry and the Registration No. of the study/trial: No. 2021K034.

Abstract Hepatocellular carcinoma (HCC) is a molecularly heterogeneous solid malignancy, and its fitness may be shaped by how its tumor cells evolve. However, ability to monitor tumor cell evolution is hampered by the presence of numerous passenger mutations that do not provide any biological consequences. Here we develop a strategy to determine the tumor clonality of three independent HCC cohorts of 524 patients with diverse etiologies and race/ethnicity by utilizing somatic mutations in cancer driver genes. We identify two main types of tumor evolution, i.e., linear, and non-linear models where non-linear type could be further divided into classes, which we call shallow branching and deep branching. We find that linear evolving HCC is less aggressive than other types. GTF2IRD2B mutations are enriched in HCC with linear evolution, while TP53 mutations are the most frequent genetic alterations in HCC with non-linear models. Furthermore, we observe significant B cell enrichment in linear trees compared to non-linear trees suggesting the need for further research to uncover potential variations in immune cell types within genomically determined phylogeny types. These results hint at the possibility that tumor cells and their microenvironment may collectively influence the tumor evolution process.

PURPOSEThe purpose is to evaluate the feasibility and efficacy of preoperative simulation results and intraoperative image fusion guidance during transjugular intrahepatic portosystemic shunt (TIPS) creation.METHODSNineteen patients were enrolled in the present study. The three-dimensional (3D) structures of the bone, liver, portal vein, inferior vena cava, and hepatic vein in the contrast-enhanced computed tomography (CT) scanning area were reconstructed in the Mimics software. The virtual Rosch–Uchida liver access set and the VIATORR stent model were established in the 3D Max software. The puncture path from the hepatic vein to the portal vein and the release position of the stent were simulated in the Mimics and 3D Max software, respectively. The simulation results were exported to Photoshop software, and the 3D reconstructed top of the liver diaphragm was used as the registration point to fuse with the liver diaphragmatic surface of the intraoperative fluoroscopy image. The selected portal vein system fusion image was overlaid on the reference display screen to provide image guidance during the operation. As a control, the last 19 consecutive cases of portal vein puncture under the guidance of conventional fluoroscopy were analyzed retrospectively, including the number of puncture attempts, puncture time, total procedure time, total fluoroscopy time, and total exposure dose (dose area product).RESULTSThe average time of preoperative simulation was about 61.26 ± 6.98 minutes. The average time of intraoperative image fusion was 6.05 ± 1.13 minutes. The median number of puncture attempts was not significantly different between the study group (n = 3) and the control group (n = 3; P = 0.175). The mean puncture time in the study group (17.74 ± 12.78 min) was significantly lower than that in the control group (58.32 ± 47.11 min; P = 0.002). The mean total fluoroscopy time was not significantly different between the study group (26.63 ± 12.84 min) and the control group (40.00 ± 23.44 min; P = 0.083). The mean total procedure time was significantly lower in the study group (79.74 ± 37.39 min) compared with the control group (121.70 ± 62.24 min; P = 0.019). The dose area product of the study group (220.60 ± 128.4 Gy. cm2) was not significantly different from that of the control group (228.5 ± 137.3 Gy. cm2; P = 0.773). There were no image guidance-related complications.CONCLUSIONThe use of preoperative simulation results and intraoperative image fusion to guide a portal vein puncture is feasible, safe, and effective when creating a TIPS. The method is cheap and may improve portal vein puncture, which may be valuable for hospitals lacking intravascular ultrasound and digital subtraction angiography (DSA) equipment equipped with a CT-angiography function.

Abstract Background 5-Methylcytosine (5mC) plays a very important role in gene stability, transcription, and development. Therefore, accurate identification of the 5mC site is of key importance in genetic and pathological studies. However, traditional experimental methods for identifying 5mC sites are time-consuming and costly, so there is an urgent need to develop computational methods to automatically detect and identify these 5mC sites. Results Deep learning methods have shown great potential in the field of 5mC sites, so we developed a deep learning combinatorial model called i5mC-DCGA. The model innovatively uses the Convolutional Block Attention Module (CBAM) to improve the Dense Convolutional Network (DenseNet), which is improved to extract advanced local feature information. Subsequently, we combined a Bidirectional Gated Recurrent Unit (BiGRU) and a Self-Attention mechanism to extract global feature information. Our model can learn feature representations of abstract and complex from simple sequence coding, while having the ability to solve the sample imbalance problem in benchmark datasets. The experimental results show that the i5mC-DCGA model achieves 97.02%, 96.52%, 96.58% and 85.58% in sensitivity (Sn), specificity (Sp), accuracy (Acc) and matthews correlation coefficient (MCC), respectively. Conclusions The i5mC-DCGA model outperforms other existing prediction tools in predicting 5mC sites, and it is currently the most representative promoter 5mC site prediction tool. The benchmark dataset and source code for the i5mC-DCGA model can be found in https://github.com/leirufeng/i5mC-DCGA .

There is a growing demand for wood as a sustainable energy source and an essential carbon sink for ecosystems. Wood formation is a dynamic process involving plant radial growth in various stages, including vascular cambial cell proliferation, xylem mother cell differentiation and expansion, secondary cell wall thickening, and programmed cell death. Wood formation is controlled by highly complex molecular regulatory networks. Identifying and analyzing the molecular mechanisms regulating key target genes is crucial for further characterizing how wood is formed. This article summarizes the current knowledge regarding wood formation and the underlying molecular regulatory mechanisms.

Bisphenols are ubiquitous chemicals used in various industries, raising concerns due to their potential to disrupt endocrine systems, particularly among occupational populations. This study concurrently assessed bisphenol A (BPA) and its 12 analogues in 325 urine samples from cashiers and non-cashiers residing in South China. Results revealed that BPA was the most prevalent bisphenol in urine, subsequent to bisphenol S (BPS), bisphenol F, bisphenol AF (BPAF) and bisphenol E (BPE), with detection frequencies at 60−99%. BPA exhibited the highest median concentration of 1.16 ng/mL. Urine samples from cashiers showed relatively high levels of BPA, BPS and BPE, highlighting potential occupational exposure implications. Variations in urinary bisphenol concentrations across gender and age groups were explored. Significant correlations were identified between urinary BPA and BPE, as well as BPS and BPAF, indicative of shared exposure sources and pathways. Cashiers had 1.50–13.4 times higher exposure than non-cashiers to these bisphenols. The median exposure to five bisphenols exceeded the established tolerable daily intake for BPA, set at 0.2 ng/kg bw/day, by 1.10–180 times. This study underscores the urgent need for assessing the potential health implications of bisphenol exposure, especially for high-exposure groups like cashiers, and suggests actions to reduce these risks.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease. Exosomes were involved in different inflammatory diseases, but their roles in CRSwNP were poorly explored. Method: We collected serum samples from 8 CRSwNP patients and 8 healthy controls (HC) and isolated their exosomes. MiRNA sequencing was performed for the exosome samples and differentially expressed miRNAs were identified. The top 3 differentially expressed exosomal miRNAs were confirmed in 2 validation cohorts, and their diagnostic values, predictive values for eosinophilic endotype, and recurrence were evaluated. Results: Distinctive serum exosomal miRNA profiles were observed between CRSwNP and HC groups. Reverse transcription-polymerase chain reaction results in the first validation cohort revealed that serum exosomal miR-141-3p levels were increased, and miR-18a-5p and miR-3679-5p levels were decreased in the CRSwNP group compared to the HC group. These 3 miRNAs were further validated in the second validation cohort, and the results showed that miR-141-3p levels were elevated and miR-3679-5p levels were reduced in the serum exosomes in the eosinophilic CRSwNP group in comparison with the non-eosinophilic CRSwNP group. Receiver operating characteristic (ROC) curves highlighted that exosomal miR-141-3p and miR-3679-5p exhibited promising values for predicting the eosinophilic endotype. The patients in the second cohort were followed up for 2 years, and categorized into recurrence and non-recurrence groups. The serum exosomal miR-141-3p levels were increased and miR-3679-5p levels were reduced in the recurrence group in comparison with the non-recurrence group. ROC curves and Kaplan-Meier survival analysis revealed significant associations between the levels of exosomal miR-141-3p and miR-3679-5p and the risk of postoperative recurrence. Conclusions: This study identified unique miRNA expression patterns in serum exosomes of CRSwNP patients. Circulating exosomal miR-141-3p and miR-3679-5p emerged as novel biomarkers for diagnosing CRSwNP, predicting the eosinophilic endotype, and forecasting postoperative recurrence.

Mental rotation (MR), a key aspect of spatial reasoning, is highly predictive of success in STEM fields. This study analyzed strategies employed by 27,600 eighth-grade students during a digital MR task from the 2017 National Assessment of Educational Progress (NAEP) in mathematics. Utilizing K-means cluster analysis to categorize behavioral and performance patterns, we identified four distinct profiles: Cognitive Offloaders (15% of the sample), Internal Visualizers (55%), External Visualizers (5%), and Non-Triers (25%). Cognitive Offloaders, skilled at minimizing cognitive load by eliminating incorrect options, demonstrated the highest MR accuracy rates at 45%. Internal Visualizers, relying less on digital tools and more on mental strategies, achieved robust performance with an average score of 38%. External Visualizers, despite their extensive use of assistive tools and greater time investment, scored an average of 36%. Non-Triers showed minimal engagement and correspondingly the lowest performance, averaging 29%. These findings not only underscore the diverse strategies students adopt in solving MR tasks but also emphasize the need for educational strategies that are tailored to accommodate different cognitive styles. By integrating MR training into the curriculum and enhancing teacher preparedness to support diverse learning needs, this study advocates for educational reforms to promote equitable outcomes in mathematics and broader STEM fields.

Summary: Platinum-based chemo-resistance is the major issue for the treatment of small cell lung cancer (SCLC). The integrative analysis of multi-omics data is a reliable approach for discovering novel biomarkers associated with chemo-resistance. Here, multi-omics integrative analysis and Cox regression found that higher expression of PCDHB4 was associated with poorer survival of SCLC patients who received chemotherapy. PCDHB4 gene was hypomethylated and upregulated in SCLC, which was validated in the levels of promoter methylation, mRNA, and protein expression. Mechanistically, using bulk RNA-seq data, functional enrichment analysis indicated that higher PCDHB4 expression was associated with lower immune infiltration. The analysis of single-cell RNA-seq (scRNA-seq) found that SCLC cells with PCDHB4 expression exhibited the characteristics of stemness and EMT. In addition, the high expression and hypomethylation of PCDHB4 were also significantly associated with poor survival in lung squamous cell carcinoma. In summary, PCDHB4 is a potential prognostic biomarker of platinum-based chemotherapy in SCLC.

A foundation for the engineering of pre-coolers is provided to understand the flow and heat transfer characteristics of air pre-coolers. Using the pre-cooler in the combustor of the Synergistic Air-Breathing Rocket Engine (SABRE) as the research object and selecting the smallest periodic unit of the model, numerical methods were adopted to study the flow field, outlet temperature, total pressure loss, heat transfer coefficient, and heat transfer power under the different number of tube rows, pitch, and helium/air heat capacity ratios. The number of tube rows increased from 7 to 15, the tube pitch increased from 1.5 mm to 3.5 mm, and the helium/air capacity ratio increased from 1.06 to 1.64. The results show that increasing the tube pitch reduces the outlet velocity and decreases the heat exchange efficiency, but the total pressure loss is reduced. Increasing the number of tube rows results in a linear increase in total pressure loss, but the heat exchange efficiency also increases. The increasing trend slows down when the number of tube rows exceeds 11. An increase in the heat capacity ratio can reduce the total pressure loss, increase the heat exchange power, and increase the amount of helium required. It can provide a reliable technical foundation for the practical engineering design of similar pre-coolers.

Eculizumab, a recombined humanized monoclonal antibody which possesses high affinity for the complement protein C5, is a therapeutic agent utilized in the treatment of atypical hemolytic uremic syndrome (aHUS) by inhibiting the terminal complement complex C5b-9. In a pediatric patient with aHUS of 14 months, the administration of eculizumab therapy was accompanied by the inclusion of meningococcal vaccine as part of the national immunization program. Notably, no other antibiotics were administered prior to or during the course of eculizumab treatment. Moreover, there were no occurrences of infusion reactions or meningococcal infections observed throughout the course of treatment. Due to the presence of anti-factor H antibodies and insufficient recovery, glucocorticoids and eculizumab were administered at week 0 and week 1, followed by the initiation of mycophenolate mofetil (MMF) at a dosage of 250 mg (approximately 548 mg/m2) per day starting from Day 10. Due to the recovered of complement antibody after 8 doses of eculizumab, the therapeutic interval was extended from once every 3 weeks to once a month since 9th administration. We experienced and successfully treated a rare case of aHUS with eculizumab in a 14-month-old Chinese pediatric patient.

ObjectiveWhile the pain threshold index (PTI) holds potential as a tool for monitoring analgesia-pain equilibrium, its precision in forecasting postoperative pain in children remains unconfirmed. This study's primary aim was to assess the PTI's predictive precision for postoperative pain.MethodsChildren (aged 2–16 years) undergoing general surgery under general anesthesia were included. Within 5 min prior to the patient's emergence from surgery, data including PTI, wavelet index (WLI), heart rates (HR) and mean arterial pressure (MAP) were collected. Subsequently, a 15-min pain assessment was conducted following the patient's awakening. The accuracy of these indicators in discerning between mild and moderate to severe postoperative pain was evaluated through receiver operating characteristic (ROC) analysis.ResultsThe analysis encompassed data from 90 children. ROC analysis showed that PTI was slightly better than HR, MAP and WLI in predicting postoperative pain, but its predictive value was limited. The area under the curve (AUC) was 0.659 [0.537∼0.780] and the optimal threshold was 65[64–67]. Sensitivity and specificity were determined at 0.90 and 0.50, respectively. In a multivariable logistic regression model, a higher predictive accuracy was found for a multivariable predictor combining PTI values with gender, BMI, HR and MAP (AUC, 0.768; 95%CI, 0.669–0.866). Upon further scrutinizing the age groups, PTI's AUC was 0.796 for children aged 9–16, 0.656 for those aged 4–8, and 0.601 for younger individuals.ConclusionsPTI, when used alone, lacks acceptable accuracy in predicting postoperative pain in children aged 2 to 16 years. However, when combined with other factors, it shows improved predictive accuracy. Notably, PTI appears to be more accurate in older children.

A silicon‐based room temperature (RT) continuous wave (CW) operation quantum well (QW) laser emitting at 850 nm is reported in this article. By applying the dislocation filter superlattice, the threading dislocation density of the GaAs pseudosubstrate on Si is reduced to 1.8 × 107 cm−2. The metal‐organic chemical vapor deposition‐grown laser structure with GaAs/GaAsP QW and InAlAs active region dislocation blocking layer are fabricated into broad‐stripe Fabry–Perot laser diodes. A typical threshold current and threshold current density of 286 mA and 715 Acm−2 are obtained with 2 mm cavity length and 20 um stripe width samples. A 94.2 mW single‐facet output power lasing around 854 nm and a 0.314 WA−1 slope efficiency is measured under RT CW operation. After a 10‐min aging process, the tested laser can operate stably under continuous operation conditions at RT and the lifetime can be approximated using an exponential fitting curve, indicating a good life reliability of this QW laser.

PurposeLiver hepatocellular carcinoma (LIHC) is the most common type of liver cancer, but there is a lack of effective indicators for its early diagnosis and prognosis, so we explored the role of KEAP1 in LIHC patients in this study.MethodsThe Cancer Genome Atlas (TCGA) dataset was used to investigate the relationship between KEAP1 expression and clinicopathological features and prognosis of LIHC patients. KEAP1 expression related pathways were enriched by Gene Ontology (GO) and gene set enrichment analysis (GSEA). Besides, KEAP1 expression-related immune infiltration was performed by single-sample GSEA (ssGSEA), and function of immune cells was detected by flow cytometry.ResultsIt was found that KEAP1 expression was significantly increased and correlated with overall survival of LIHC patients. A total of 231 differentially expressed genes (DEGs) between LIHC patients with high- and low-KEAP1 expression were found, which associated with various biological pathways. Besides, KEAP1 expression was positively correlated with the infiltration level of T helper cells and Th2 cells but negatively correlated with DCs and cytotoxic cells. Functional analysis revealed that the expression of IL 4 in Th2 cells and CD107a, GrA and GrB in cytotoxic cells was significantly greater in LIHC patients than in HCs. In addition, KEAP1 expression was closely correlated with liver function in LIHC patients.ConclusionHighly expressed KEAP1 was closely related to the diagnosis, prognosis, immune cell infiltration, and liver function of LIHC, which might promote the progression of LIHC through regulating cell development, signal transduction, and abnormal immune response. The current study partially revealed the role of KEAP1 in LIHC and provided a potential biomarker for the diagnosis, prognosis and treatment of LIHC.

Students' demand for online learning has exploded during the post-COVID-19 pandemic era. However, due to their poor learning experience, students' dropout rate and learning performance of online learning are not always satisfactory. The technical advantages of Beyond Fifth Generation (B5G) can guarantee a good multimedia Quality of Experience (QoE). As a special case of multimedia services, online learning takes into account both the usability of the service and the cognitive development of the users. Factors that affect the Quality of Online Learning Experience (OL-QoE) become more complicated. To get over this dilemma, we propose a systematic scheme by integrating big data, Machine Learning (ML) technologies, and educational psychology theory. Specifically, we first formulate a general definition of OL-QoE by data analysis and experimental verification. This formula considers both the subjective and objective factors (i.e., video watching ratio and test scores) that most affect OL-QoE. Then, we induce an extended layer to the classic Broad Learning System (BLS) to construct an Extended Broad Learning System (EBLS) for the students' OL-QoE prediction. Since the extended layer can increase the width of the BLS model and reduce the redundant nodes of BLS, the proposed EBLS can achieve a trade-off between the prediction accuracy and computation complexity. Finally, we provide a series of early intervention suggestions for different types of students according to their predicted OL-QoE values. Through timely interventions, their OL-QoE and learning performance can be improved. Experimental results verify the effectiveness of the proposed scheme.

Abstract Background Postoperative pain is common in pediatric urological surgery. The study assess the impact of perioperative intravenous infusion of low-dose esketamine on postoperative pain in pediatric urological surgery. Methods Pediatric patients (n = 80) undergoing urological surgery were randomized into four groups. Patients in the control group were administered an analgesic pump containing only hydromorphone at a dose of 0.1 mg/kg (Hydromorphone Group 1, H1) or 0.15 mg/kg (Hydromorphone Group 2, H2). Patients in the experimental group were injected intravenously with 0.3 mg/kg of esketamine (Esketamine group 1, ES1) or equal volume of saline (Esketamine Group 2, ES2) during anesthesia induction. Esketamine 1.0 mg/kg and hydromorphone 0.1 mg/kg were added to the analgesic pump. Face, Leg, Activity, Crying, and Comfort (FLACC) scale or the Numerical Rating Scale (NRS) and adverse effects were recorded at 2, 6, 24, and 48 h postoperatively. Additionally, total and effective PCA button presses were recorded. Results In comparison to the H1 group, the pain scores were notably reduced at all postoperative time points in both the ES1 and H2 groups. The ES2 group exhibited lower pain scores only at 24 and 48 h postoperatively. When compared to the H2 group, there were no significant differences in pain scores at various postoperative time points in the ES2 group. However, the ES1 group demonstrated significantly lower pain scores at 6, 24 and 48 h postoperatively, and these scores were also significantly lower than those observed in the ES2 group. The total and effective number of PCA button presses in the ES1, ES2 and H2 group were lower than that in the H1 group (P