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Abstract This article presents a novel methodology to maximize wind farm power generation by integrating graph neural networks (GNN), supervised learning, and reinforcement learning techniques. First, the article introduces a graph‐based representation of the wind farm, capturing wind turbines as vertices and the inter‐turbine wake interactions as edges. The construction of this graph representation integrates the Jensen wake model, which includes insights derived from prior knowledge of wind farm aerodynamics. Subsequently, a detailed description of the GNN model's architecture, incorporating a message passing mechanism, is outlined. This GNN model is trained initially with supervised learning using a dataset of optimal pitch angles generated from the analytical results derived from Jensen wake model. Moreover, to improve the GNN model's accuracy and adaptability, reinforcement learning techniques are employed. The GNN model interacts with a high‐fidelity wind farm simulation environment, receiving feedback in the form of rewards derived from the wind farm's actual power output. Through a policy gradient approach, the GNN parameters undergo iterative updates, enabling the model to learn and adapt to dynamic wind conditions and intricate turbine interactions. The effectiveness and advantages of the proposed methodology are demonstrated through comprehensive case studies across various wind farm layouts.

Abstract Background Although there is a high incidence of hematogenous infections in melioidosis, a tropical infectious disease, there are few systematic analyses of hematogenous melioidosis in imaging articles. A comprehensive clinical and imaging evaluation of hematogenous melioidosis be conducted in order to achieve early diagnosis of the disease. Materials and methods We conducted an analysis of 111 cases of melioidosis diagnosed by bacteriological culture between August 2001 and September 2022. The analysis focused on observing the main manifestations of chest imaging and clinical data, including nodules, cavities, consolidation, ground glass opacity(GGO), pleural effusion, centrilobular nodules, and temperature, leucocyte count, diabetes, etc. Our study involved univariate and multivariate analyses to identify significant diagnostic variables and risk predictive factors. Results A total of 71.2% (79/111) of melioidosis cases were caused by hematogenous infection, and the most common organ involved was the lungs (88.5%, 100/113). The incidence of sepsis in patients with lung abnormalities was high (73%, 73/100), and the mortality rate of septic shock was 22% (22/100). Univariate analysis showed that the radiologic signs of blood culture-positive cases were more likely to have bilateral pulmonary and subpleural nodules (p = 0.003), bilateral GGO (p = 0.001), bilateral hydrothorax (p = 0.011). The multivariate analysis revealed a significant improvement in the area under the receiver operating characteristic curve (AUC) when comparing the model that included both clinical and radiologic variables to the model with clinical variables alone. The AUC increased from 0.818 to 0.932 (p = 0.012). The most important variables in the logistic regression with backward elimination were found to be nodule, GGO, and diabetes. Conclusion The combination of CT features and clinical variables provided a valuable and timely warning for blood borne infectious melioidosis.

Abstract Introduction Sub-Saharan Africa has a high burden of HIV, particularly among female sex workers (FSW) and men who have sex with men (MSM). Future clinical trials to evaluate vaccines and other interventions to prevent HIV will need to enroll populations with high HIV incidence. We conducted an observational study of HIV incidence among men and women with multiple sexual partners—including MSM and FSW—in Maputo, Mozambique, in order to prepare the country to conduct future efficacy trials of candidate HIV vaccines and other HIV prevention products. Methods We conducted a prospective observational HIV incidence study in Maputo, Mozambique, that enrolled adults aged 18–35 years, without HIV, who had two or more sexual partners in the preceding three months. Recruitment strategies prioritized participation of MSM and FSW. Participants were followed for 24 months with HIV-1 testing every 3 months and staff-administered behavioral questionnaires every 6 months. Cox proportional hazard modeling was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for factors potentially associated with HIV acquisition. Results From January 2014 to October 2017, 505 adults without HIV were enrolled with median age of 21 years (interquartile range:19–24); 41% were female and 82% were single. There were 19 HIV seroconversions (10 female and 9 male) during 943 person-years (PY) of observation (overall HIV incidence 2.02/100PY; 95%CI 1.21–3.15). The highest HIV incidence was observed among sex workers (2.08/100PY; 95%CI 0.25–7.52) and MSM (19.18/100PY; 95%CI 3.96–56.06). Increased hazard of incident HIV was observed among participants who were MSM (HR = 27.95, 95%CI 4.39–117.94), p = 0.0004), reported three or more sexual partners at enrollment (HR = 7.39, 95%CI 1.64–33.25, p = 0.009), and indicated ever having a sexual partner living with HIV (HR = 9.64, 95%CI 2.23–41.71, p = 0.002). Conclusion Our findings may inform inclusion criteria for upcoming clinical trials of HIV prevention interventions, including vaccine candidates, which may prioritize enrollment of MSM, people with more than three sexual partners, and people with sexual partners who are living with HIV. These same populations are in need of further intervention to reduce HIV incidence.

Abstract Background Hypertension continues to increase in prevalence, and it has become a major cause of increased mortality globally. Physical activity (PA) has been shown to be a first-line treatment for controlling blood pressure. However, participation rates in PA are still poor. Therefore, it’s imperative to explore the factors that affect patient PA adherence. Methods A synthesis of qualitative research of the PA experience of patients with hypertension was conducted. We systematically searched for qualitative studies published in English from inception to May 2023 in the databases of PubMed, Embase, Web of Science, CINAHL, PsycINFO, and Cochrane Library. The Joanna Briggs Institute tool was used to extract data, and the Capability, Opportunity, Motivation-Behaviour model was used to synthesize data. Results This qualitative research included 17 studies, identified 85 findings, summarized 9 categories, and finally meta-aggregated 3 synthesized findings, including capabilities of patients with hypertension, PA opportunities and PA motivators. The capabilities included age, other health problems, and PA knowledge and skills. Opportunities included time constraints, environmental factors, physical activity resources, and social support. Motivators included self-efficacy, pursuing physical health, and experience from PA. Conclusion The available evidence contributes to a comprehensive understanding of the barriers and facilitators of PA in patients with hypertension. Most of these barriers can be addressed and improved. When designing and implementing physical activity programs for patients with hypertension, an individualized PA program should first be designed, tailored to the patient’s capacity. Secondly, patients should be provided with additional PA resources and enhanced social support. Lastly, patients’ motivation can be increased by enhancing their PA experience.

Abstract Frictional vibration often occurs during sliding, commonly referred to as the stick-slip phenomenon. It is more likely to occur in the range of the Stribeck curve, where friction and velocity have negative gradient characteristics. In this study, ultrasonic vibration is applied to the metal/metal sliding friction pair which reduce both static and kinetic friction forces. The inhibition mechanism of ultrasonic vibration on the stick-slip phenomenon is investigated for a sliding pair moving at low velocities (0.05–1.0 mm/s) under the condition of dry friction and oil lubrication. Under the condition of dry friction, ultrasonic vibration reduces the slider’s friction force by up to 89%, and the displacement fluctuation by up to 61%, effectively inhibiting the stick-slip phenomenon. Under the condition of oil lubrication, the friction force fluctuates when driving at a constant velocity, and the displacement fluctuation also fluctuates with the change of driving velocities. After ultrasonic vibration is applied, the friction reduction of the slider changes greatly with the driving velocity, so that the inhibition effect of ultrasonic vibration on stick-slip phenomenon under oil lubrication condition is unstable.

BackgroundWith the improvement of living standards, an increasing number of patients are presenting with mixed hyperlipidemia. In addition to cholesterol reduction, it is imperative to lower triglyceride levels. The combination of statin and fibrate for reducing lipid levels has commonly been applied in clinical therapy. However, the combination of drugs also increases the risk of adverse events (AEs). In this study, we analyzed the safety signals of rosuvastatin-fenofibrate combination by assessing the publicly available US Food and Drug Administration Adverse Event Reporting System (FAERS), so as to provide a reference for rational clinical use of rosuvastatin and fenofibrate, and reduce the occurrence of related AEs.MethodsReports to the FAERS from 1 January 2004 to 19 March 2020 were analyzed. The proportional report ratio (PRR), reporting odds ratio (ROR), and Bayesian Confidence Propagation Neural Network (BCPNN) analysis were used to extract data from FAERS for suspected signals referring to the combination of rosuvastatin and fenofibrate.ResultsA total of 68 safety signals were detected from the top 250 AEs in 3,587 reports, of which 28 signals were not included in the drug labels. All the detected AEs were associated with 12 System Organ Classes (SOC), such as gastrointestinal, musculoskeletal and connective tissue, general diseases, investigations and nervous system. The most frequent AEs were analyzed, and it was found that women generally have a higher susceptibility to experiencing AEs, including pain, nausea, fatigue, myalgia, diarrhea, dyspnea, headache, weakness, and dizziness.ConclusionClinicians should pay more attention to the AEs of gastrointestinal and muscular system during combination therapy, and it is recommended to strengthen pharmaceutical care during clinical application.

ObjectiveEndometriosis (EMs) is a chronic inflammatory disease characterized by the presence of endometrial tissue in the non-uterine cavity, resulting in dysmenorrhea, pelvic pain, and infertility. Epidemiologic data have suggested the correlation between EMs and recurrent pregnancy loss (RPL), but the pathological mechanism is unclear. This study aims to investigate the potential biomarkers and immune infiltration in EMs and RPL, providing a basis for early detection and treatment of the two diseases.MethodsTwo RPL and six EMs transcriptomic datasets from the Gene Expression Omnibus (GEO) database were used for differential analysis via limma package, followed by weighted gene co-expression network analysis (WGCNA) for key modules screening. Protein-protein interaction (PPI) network and two machine learning algorithms were applied to identify the common core genes in both diseases. The diagnostic capabilities of the core genes were assessed by receiver operating characteristic (ROC) curves. Moreover, immune cell infiltration was estimated using CIBERSORTx, and the Cancer Genome Atlas (TCGA) database was employed to elucidate the role of key genes in endometrial carcinoma (EC).Results26 common differentially expressed genes (DEGs) were screened in both diseases, three of which were identified as common core genes (MAN2A1, PAPSS1, RIBC2) through the combination of WGCNA, PPI network, and machine learning-based feature selection. The area under the curve (AUC) values generated by the ROC indicates excellent diagnostic powers in both EMs and RPL. The key genes were found to be significantly associated with the infiltration of several immune cells. Interestingly, MAN2A1 and RIBC2 may play a predominant role in the development and prognostic stratification of EC.ConclusionWe identified three key genes linking EMs and RPL, emphasizing the heterogeneity of immune infiltration in the occurrence of both diseases. These findings may provide new mechanistic insights or therapeutic targets for further research of EMs and RPL.

IntroductionGuillain-Barré syndrome (GBS) is a rare, immune-mediated polyneuropathy primarily affecting the peripheral nervous system. Diagnosis is often supported by neuroconduction studies showing polyradiculoneuropathy and cerebrospinal fluid (CSF) analysis revealing albumin-cytological dissociation. However, these features may not appear in the early stages, leading to potential misdiagnosis. The central nervous system (CNS) is generally not affected due to differences in antigen expression, optic neuritis (ON), a demyelinating inflammation of the optic nerve, occasionally co-occurs with GBS as a rare variant. Although GBS can manifest with various neurological symptoms, the co-occurrence of optic neuritis (ON) is rare, especially in pediatric cases. This report documents the first known case in China of a child with severe GBS complicated by ON, which developed following an upper respiratory infection.Case presentationA 14-year-old male presented with acute progressive quadriparesis and visual impairment following a febrile illness. On admission, he displayed severe respiratory and autonomic instability requiring mechanical ventilation. Neurological examination revealed flaccid paralysis of all four limbs with absent reflexes, along with bilateral optic neuritis, confirmed by MRI showing inflammation of the optic nerve. Initial cerebrospinal fluid (CSF) analysis was normal, but subsequent testing revealed elevated protein levels typical of GBS. Neurophysiological studies indicated widespread demyelinating and axonal damage.Interventions and outcomesThe patient received intravenous immunoglobulin (IVIG) therapy, high-dose corticosteroids, and, given the severe progression, rituximab. Despite initial worsening, gradual improvement in muscle strength and visual acuity was observed over several weeks. At three months, the patient was discharged with significantly restored function, with muscle strength nearing baseline and partial visual recovery.ConclusionThis case highlights the clinical complexity of GBS with ON in pediatric patients, emphasizing the importance of timely immunomodulatory treatment. It also underscores the need for awareness of overlapping central and peripheral autoimmune neuropathies to improve diagnostic accuracy and patient outcomes.

Harmful algal blooms (HABs), exacerbated by climate change and environmental disturbances, pose global challenges due to marine toxin contamination, particularly diarrhetic shellfish toxins (DSTs). DSTs are prevalent marine toxins, and understanding their synthesis is vital for managing fisheries and mitigating environmental triggers. This study delves into the synthesis mechanisms of DSTs in Prorocentrum arenarium and Prorocentrum lima, which vary in toxin types and concentrations. We conducted a comprehensive comparative transcriptomic analysis to identify potential toxin-related genes, focusing on polyketide synthases (PKSs) and fatty acid synthases (FASs). Our research predicted 96 PKSs and 91 FASs genes, with a detailed examination of their sequences to elucidate dinophysistoxins (DTXs) synthesis. Additionally, we analyzed differential gene expression of PKSs in P. arenarium under nitrogen and phosphorus-limited conditions, revealing a correlation between specific PKSs gene expression patterns and okadaic acid (OA) content variations. These findings suggest a potential role of the fatty acid biosynthesis pathway in DSTs synthesis. While not completely uncovering the biosynthetic pathway of DSTs, our study offers crucial insights and genomic resources for future research on dinoflagellate toxin production mechanisms.

IntroductionThis study investigates Mandarin-speaking children's acquisition of aspirated/unaspirated voiceless consonants in terms of perception and production, to track children's developmental profile and explore the factors that may affect their acquisition, as well as the possible association between perception and production.MethodsMandarin-speaking children (N = 95) aged 3–5 and adults (N = 20) participated in (1) a perception test designed based on the minimal pairs of unaspirated/aspirated consonants in the quiet and noisy conditions respectively; (2) a production test where participants produced the target words, with syllable-initial consonants focusing on aspiration and non-aspiration. Six pairs of unaspirated/aspirated consonants in Mandarin were included.Results(1) Children's perception and production accuracy of aspirated and unaspirated consonants increased with age. Five-year-olds achieved high accuracy in the perception under the quiet condition and in the production (over 90%), though not yet adult-like. (2) Noise adversely affected children's perception, with all child groups showing poor performance in the noisy condition. In terms of perception, stops were more challenging to children than affricates, but in terms of production, children performed better on stops. Furthermore, the presence of noise had a greater detrimental effect on the perception of aspirated consonants compared to unaspirated ones. (3) A weak positive correlation was found between children's perception of consonant aspiration in the quiet condition and their production.DiscussionThe findings indicate that age, aspiration state, and manner of articulation (MOA) would affect children's acquisition of consonant aspiration. Although 5-year-olds have almost acquired aspirated/unaspirated consonants, compared to adults, the perception of consonant aspiration in noise remains a challenge for children.

Flavor components largely depend on microbial activity and environmental conditions during traditional fermented food production. However, the microbial and abiotic contributions to the flavor of Chinese strong-aroma Baijiu (SAB) remain poorly understood. In this study, the composition and functional profiles of the fungal and bacterial communities changed significantly after fourteen days of grain fermentation. Acetilactobacillus jinshanensis, Issatchenkia orientalis and Kazachstani humilis became the dominant species as fermentation proceeded. Pathways related to lipid, protein and secondary metabolite metabolism were enriched during the middle and later stages of grain fermentation. Ethyl caproate, hexyl caproate, and ethyl lactate were identified as the main volatile components in fermented grain. Lactobacillus species were significantly related to volatile components. Compared with fungi, bacterial diversity accounted for 96 % of the variation in volatile components coupled with temperature, acidity and reducing sugar. This work provides insights into the production optimization and flavor enhancement of SAB by optimizing abiotic factors and microbial compositions.

AbstractBackground Circulating plasma cells (CPCs) are defined by the presence of peripheral blood clonal plasma cells, which would contribute to the progression and dissemination of multiple myeloma (MM). An increasing number of studies have demonstrated the predictive potential of CPCs in the past few years. Therefore, there is a growing need for an updated meta-analysis to identify the specific relationship between CPCs and the prognosis of MM based on the current research status.Methods The PubMed, Embase, and Cochrane Library databases were screened to determine eligible studies from inception to November 5, 2023. Publications that reported the prognostic value of CPCs in MM patients were included. Hazard ratios (HRs) with 95% confidence intervals (CIs) of overall survival (OS) and progression-free survival (PFS) were extracted to pool the results. Subgroup analyses were performed based on region, sample size, cut-off value, detection time, initial treatment, and data type. The association between CPCs level and clinicopathological characteristics, including the International Staging System (ISS), Revised-ISS (R-ISS), and cytogenetic abnormalities were also evaluated. Statistical analyses were conducted using STATA 17.0 software.Results Twenty-two studies with a total of 5637 myeloma patients were enrolled in the current meta-analysis. The results indicated that myeloma patients with elevated CPCs were expected to have a poor OS (HR = 2.19, 95% CI: 1.81–2.66, p

Nickel-rich layered Li transition metal oxides are the most promising cathode materials for high-energy-density Li-ion batteries. However, they exhibit rapid capacity degradation induced by transition metal dissolution and structural reconstruction, which are associated with hydrofluoric acid (HF) generation from lithium hexafluorophosphate decomposition. The potential for thermal runaway during the working process poses another challenge. Separators are promising components to alleviate the aforementioned obstacles. Herein, an ultrathin double-layered separator with a 10 μm polyimide (PI) basement and a 2 μm polyvinylidene difluoride (PVDF) coating layer is designed and fabricated by combining a non-solvent induced phase inversion process and coating method. The PI skeleton provides good stability against potential thermal shrinkage, and the strong PI–PVDF bonding endows the composite separator with robust structural integrity; these characteristics jointly contribute to the extraordinary mechanical tolerance of the separator at elevated temperatures. Additionally, unique HF-scavenging effects are achieved with the formation of –CO···H–F hydrogen bonds for the abundant HF coordination sites provided by the imide ring; hence, the layered Ni-rich cathodes are protected from HF attack, which ultimately reduces transition metal dissolution and facilitates long-term cyclability of the Ni-rich cathodes. Li||NCM811 batteries (where “NCM” indicates LiNixCoyMn1−x−yO2) with the proposed composite separator exhibit a 90.6% capacity retention after 400 cycles at room temperature and remain sustainable at 60 °C with a 91.4% capacity retention after 200 cycles. By adopting a new perspective on separators, this study presents a feasible and promising strategy for suppressing capacity degradation and enabling the safe operation of Ni-rich cathode materials.

Abstract Background Previous studies have shown that peptides encoded by noncoding RNAs (ncRNAs) can be used as peptide drugs to alleviate diseases. We found that microRNA-31 (miR-31) is involved in the regulation of hypertension and that the peptide miPEP31, which is encoded by the primary transcript of miR-31 (pri-miR-31), can inhibit miR-31 expression. However, the role and mechanism of miPEP31 in hypertension have not been elucidated. Methods miPEP31 expression was determined by western blot analysis. miPEP31-deficient mice (miPEP31−/−) were used, and synthetic miPEP31 was injected into Ang II-induced hypertensive mice. Blood pressure was monitored through the tail-cuff method. Histological staining was used to evaluate renal damage. Regulatory T (Treg) cells were assessed by flow cytometry. Differentially expressed genes were analysed through RNA sequencing. The transcription factors were predicted by JASPAR. Luciferase reporter and electrophoretic mobility shift assays (EMSAs) were used to determine the effect of pri-miR-31 on the promoter activity of miPEP31. Images were taken to track the entry of miPEP31 into the cell. Results miPEP31 is endogenously expressed in target organs and cells related to hypertension. miPEP31 deficiency exacerbated but exogenous miPEP31 administration mitigated the Ang II-induced systolic blood pressure (SBP) elevation, renal impairment and Treg cell decreases in the kidney. Moreover, miPEP31 deletion increased the expression of genes related to Ang II-induced renal fibrosis. miPEP31 inhibited the transcription of miR-31 and promoted Treg differentiation by occupying the Cebpα binding site. The minimal functional domain of miPEP31 was identified and shown to regulate miR-31. Conclusion miPEP31 was identified as a potential therapeutic peptide for treating hypertension by promoting Treg cell differentiation in vivo. Mechanistically, we found that miPEP31 acted as a transcriptional repressor to specifically inhibit miR-31 transcription by competitively occupying the Cebpα binding site in the pri-miR-31 promoter. Our study highlights the significant therapeutic effect of miPEP31 on hypertension and provides novel insight into the role and mechanism of miPEPs.

Abstract The inactivation of natural enzymes by radiation poses a great challenge to their applications for radiotherapy. Single-atom nanozymes (SAzymes) with high structural stability under such extreme conditions become a promising candidate for replacing natural enzymes to shrink tumors. Here, we report a CuN3-centered SAzyme (CuN3-SAzyme) that exhibits higher peroxidase-like catalytic activity than a CuN4-centered counterpart, by locally regulating the coordination environment of single copper sites. Density functional theory calculations reveal that the CuN3 active moiety confers optimal H2O2 adsorption and dissociation properties, thus contributing to high enzymatic activity of CuN3-SAzyme. The introduction of X-ray can improve the kinetics of the decomposition of H2O2 by CuN3-SAzyme. Moreover, CuN3-SAzyme is very stable after a total radiation dose of 500 Gy, without significant changes in its geometrical structure or coordination environment, and simultaneously still retains comparable peroxidase-like activity relative to natural enzymes. Finally, this developed CuN3-SAzyme with remarkable radioresistance can be used as an external field-improved therapeutics for enhancing radio-enzymatic therapy in vitro and in vivo. Overall, this study provides a paradigm for developing SAzymes with improved enzymatic activity through local coordination manipulation and high radioresistance over natural enzymes, for example, as sensitizers for cancer therapy.

BackgroundIn the past decade, the application of machine learning (ML) in the clinical management of acute upper gastrointestinal bleeding (AUGIB) has received much attention and has become a hot research topic. However, no scientometric report has systematically summarized and outlined the research progress in this field.ObjectiveThis study aims to utilize bibliometric analysis methods to delve into the applications of machine learning in AUGIB and the collaborative network behind it over the past decade. Through a thorough analysis of relevant literature, we uncover the research trends and collaboration patterns in this field, which can provide valuable references and insights for further in-depth exploration in the same field.MethodsUsing the Web of Science (WOS) as the data source, this study explores academic development in a specific field from December 2013 to December 2023. The search strategy included terms related to “Machine Learning” and “Acute Upper Gastrointestinal Bleeding”. Only original articles in English focusing on ML in AUGIB were included. The analysis of downloaded literature with Citespace software, including keyword co-occurrence, author collaboration networks, and citation relationship networks, reveals academic dynamics, research hotspots, and collaboration trends.ResultsAfter sorting and compiling, we have collected 73 academic papers written by 217 authors from 133 institutions in 29 countries worldwide. Among them, China and AM J GASTROENTEROL have made significant contributions in this field, providing many high-quality research achievements. The study found that these papers mainly focus on three core research hotspots: deepening clinical consensus, precise analysis of medical images, and optimization of data integration and decision support systems.ConclusionsThis study summarizes the latest advancements in the application of machine learning to AUGIB research. Through bibliometric analysis and network visualization, it reveals emerging trends, origins, leading institutions, and hot topics in this field. While this area has already demonstrated significant potential in medical artificial intelligence, our findings will provide valuable insights for future research directions and clinical practices.

The rapid advancement of power electronics technology has led to the development of more flexible DC transmission systems, revealing the issue of oscillations. In this paper, a novel impedance modeling approach for the DC side of Modular Multilevel Converters (MMCs) has been introduced to overcome the limitations of previous methods, which did not take into account the complete control structure and internal harmonic characteristics. An accurate impedance model has been established, integrating the types of disturbance signal sources used in impedance measurement and the impact of measurement device characteristics on model accuracy. This approach enhances the precision of impedance stability analysis, which is crucial for system stability. The model’s effectiveness has been validated through simulations, demonstrating the influence of disturbance signal types and measurement device characteristics on the impedance stability of the MMC’s DC side.

Melon seeds have received considerable attention in recent years because of their high protein content, but they have not yet been fully used. The modification of melon seed protein (MSP) using ultrasound-assisted pH-shifting treatment was investigated in this study by analyzing structural characteristics and functional properties. The particle size, free sulfhydryl content, surface hydrophobicity, solubility, secondary structure, water-holding capacity, oil-holding capacity, emulsification activity index, and emulsification stability index of MSP were determined. MSP treated with ultrasound-assisted, pH-shifting had a smaller particle size, lower free sulfhydryl content, higher surface hydrophobicity, and solubility increased from 43.67 % to 89.12 %. The secondary structure of MSP was affected by ultrasonic treatment, manifesting as an α-helix increase and β-helix, β-turn, and random coil content decrease, which may be the reason why the protein structure became more compact after treatment. The water and oil holding capacities of MSP increased from 2.74 g/g and 3.14 g/g in untreated samples to 3.19 g/g and 3.97 g/g for ultrasound-treated samples, and further increased to 3.97 g/g and 5.02 g/g for ultrasound-assisted, pH-shifting treatment at pH 9.0, respectively. The emulsification activity index of MSP was 21.11 m2/g before treatment and reached a maximum of 32.34 m2/g after ultrasound-assisted, pH-shifting treatment at pH 9.0. The emulsification stability of MSP was maximized by ultrasonic treatment at pH 7.0. Ultrasound-assisted, pH-shifting treatment can effectively improve the functional properties of MSP by modifying the protein structure, which improves the potential application of melon seed protein in the food industry.

BackgroundPlatelets can dynamically regulate tumor development and progression. Nevertheless, research on the predictive value and specific roles of platelets in gastric cancer (GC) is limited. This research aims to establish a predictive platelets-related gene signature in GC with prognostic and therapeutic implications.MethodsWe downloaded the transcriptome data and clinical materials of GC patients (n=378) from The Cancer Genome Atlas (TCGA) database. Prognostic platelets-related genes screened by univariate Cox regression were included in Least Absolute Shrinkage and Selection Operator (LASSO) analysis to construct a risk model. Kaplan-Meier curves and receiver operating characteristic curves (ROCs) were performed in the TCGA cohort and three independent validation cohorts. A nomogram integrating the risk score and clinicopathological features was constructed. Functional enrichment and tumor microenvironment (TME) analyses were performed. Drug sensitivity prediction was conducted through The Cancer Therapeutics Response Portal (CTRP) database. Finally, the expression of ten signature genes was validated by quantitative real-time PCR (qRT-PCR).ResultsA ten-gene (SERPINE1, ANXA5, DGKQ, PTPN6, F5, DGKB, PCDH7, GNG11, APOA1, and TF) predictive risk model was finally constructed. Patients were categorized as high- or low-risk using median risk score as the threshold. The area under the ROC curve (AUC) values for the 1-, 2-, and 3-year overall survival (OS) in the training cohort were 0.670, 0.695, and 0.707, respectively. Survival analysis showed a better OS in low-risk patients in the training and validation cohorts. The AUCs of the nomogram for predicting 1-, 2-, and 3-year OS were 0.708, 0.763, and 0.742, respectively. TME analyses revealed a higher M2 macrophage infiltration and an immunosuppressive TME in the high-risk group. Furthermore, High-risk patients tended to be more sensitive to thalidomide, MK-0752, and BRD-K17060750.ConclusionThe novel platelets-related genes signature we identified could be used for prognosis and treatment prediction in GC.

Background: Endoscopy is important for the diagnosis and treatment of acute upper gastrointestinal bleeding (AUGIB), especially acute variceal bleeding (AVB), in liver cirrhosis. However, the optimal timing of endoscopy remains controversial, primarily because the currently available evidence is of poor quality, and the definition of early endoscopy is also very heterogeneous among studies. Herein, a multicenter randomized controlled trial (RCT) is performed to explore the impact of the timing of endoscopy on the outcomes of cirrhotic patients with AVB. Methods: A total of 368 cirrhotic patients presenting with AUGIB who are highly suspected to be from AVB will be enrolled. They will be stratified according to the severity of liver function and clinical presentation at admission and then randomly assigned at a 1:1 ratio into early (within 12 h after admission) and delayed (within 12–24 h after admission) endoscopy groups within each stratum. The primary outcomes include the rates of 5-day failure to control bleeding after admission and 6-week rebleeding. The secondary outcomes include 6-week mortality and incidence of adverse events. Conclusion: Considering existing evidence originates from non-randomized studies, this RCT will provide high-quality evidence to uncover whether cirrhotic patients with AVB should undergo early endoscopy to control bleeding and improve survival. Trial registration: ClinicalTrials.gov identifier: NCT06031402.

ABSTRACT Background Laryngeal squamous cell carcinoma (LSCC) is a type of cancer of the respiratory tract that often presents with subtle symptoms at the early stage and is susceptible to recurrence and metastasis. Materials and Methods To find out key regulatory genes involved in LSCC development, we downloaded LSCC‐related sequencing datasets for bioinformatics analysis. WGCNA was performed on GSE142083 and differential analysis was conducted on GSE51985 and TCGA‐HNSC. Intersection genes were taken from the above three datasets. To confirm the function of genes, we overexpressed and knocked down genes in cells and treated them with autophagy agonist Rapamycin and PI3K‐AKT pathway inhibitor. At the cellular level, the expression of CH25H, autophagy‐related proteins (LC3 I, LC3 II, p62, and Beclin 1), and PI3K‐AKT pathway‐related proteins (PI3K, AKT, and p‐AKT) were assessed via Western blot; the mRNA level of CH25H was evaluated through qRT‐PCR; the cell activity was examined by CCK8; the apoptosis was assessed through flow cytometry; and the cell migration and invasion were assessed through wound healing and Transwell assays. Results Through bioinformatics analysis, we screened 7 genes (CH25H, NELL2, STC2, TMEM158, ZIC2, HOXD11, and HOXD10). Ultimately, CH25H was selected for follow‐up experiments. By detecting CH25H expression in human immortalized keratinocytes (HaCaT) and LSCC cells (Tu‐686, SNU899, and AMC‐HN‐8), it was found out that CH25H expression was higher in HaCaT cells than in LSCC cells. To elucidate the role of CH25H in LSCC development, we overexpressed CH25H in Tu‐686 cells and downregulated its expression in AMC‐HN‐8 cells. CH25H was revealed to reduce the proliferation, activity, invasion, and migration of LSCC cells while increasing their apoptosis levels. Significant changes were also observed in the expressions of autophagy‐ and PI3K‐AKT pathway‐related proteins. To further investigate the roles of autophagy and the PI3K‐AKT pathway in LSCC development, we respectively employed autophagy agonists and inhibitors targeting the PI3K‐AKT pathway to intervene the cells, and found that CH25H regulated the PI3K‐AKT pathway to promote autophagy, thus enhancing the apoptosis of LSCC cells. We further investigated CH25H's impact on tumor growth, autophagy, and the PI3K‐AKT pathway at the animal level and found that CH25H promoted autophagy of LSCC cells and inhibited the PI3K‐AKT pathway, and ultimately inhibiting the progression of LSCC. Conclusions In summary, CH25H promotes autophagy and affects the malignant progression of LSCC through the PI3K‐AKT pathway.

Solid Rocket Motors (SRMs) rely on solid propellants, directly impacting the energy capacity of launch vehicles. High energy density material (HEDM) propellant exhibits superior energy density owing to the incorporation of a substantial quantity of energetic particles. However, the elevated particle fill ratio makes the formation of pores more prevalent during the manufacturing process of propellants. These pores, representing default defects, are indispensable factors in the investigation of mechanical properties of propellants. This study investigated default defects effects on HEDM propellants, analyzing both microscopic and macroscopic perspectives. Utilizing micro-CT imaging, the microstructure and default defects were characterized. Subsequently, using the cohesive zone model (CZM), microscopic damage evolution was depicted with the representative volume element (RVE) model, allowing in-depth analysis. Furthermore, a damage constitutive model, based on microscopic damage, was developed, with its softening function calibrated using microscopic damage evolution characteristics. Implemented into ABAQUS via user-defined material subroutine (UMAT), this model enabled the prediction of the mechanical response of HEDM propellants with different defects. The results demonstrate that the developed model accurately predicts the mechanical responses of HEDM propellants with different defects, showcasing the potential of macro-microscopic approaches in analyzing propellants with default defects.

Abstract Background Self-directed learning (SDL) ability is the basis for cultivating nursing students’ ability to find and solve problems, lifelong learning, and providing high-quality nursing talents for healthcare. The O-AMAS (Objective, Activation, Multi-learning, Assessment, Summary) model adheres to the teaching philosophy of student-centered, result-oriented, combines the advantages of online and offline teaching, enriching teaching resources and learning channels, diversifying teaching and evaluation methods, and emphasizing integrating and applying knowledge conducive to improving students’ SDL ability and achieving teaching objectives. This study explored the course design, practical, and application effects under the O-AMAS effective teaching model in internal medicine nursing to provide a basis and reference for combining effective teaching models with blended teaching in future nursing courses. Methods This study is a self-controlled before-after trial. The participants were 76 nursing undergraduates from Hunan Normal University. This study utilizes the O-AMAS effective teaching model to design internal medicine nursing courses and implement blended online and offline teaching. Main links: The overall course design and application are student-centered, after clarifying macro and micro multi-dimensional learning objectives, with online and offline blended teaching environments activated students’ learning behavior and diversified teachers’ teaching activities, then based on instant and dynamic provide effective feedback; finally, students take the initiate to make a brief and potent summary under the teacher guidance. After the course, a unified assessment of the learning effect of nursing students was conducted, including the evaluation of the SDL ability of nursing students, a final comprehensive evaluation grade, and a teaching satisfaction survey. Results The nursing students’ SDL ability scores are higher than before teaching, and the results were statistically significant (P

Abstract Background Although physician-pharmacist collaborative clinics for diabetes management have been shown to be effective and cost-effective worldwide, there is limited understanding of the factors that influence their sustainable implementation. This study aims to identify the associated factors and provide sustainability strategy to better implement physician-pharmacist collaborative clinics for diabetes management in primary healthcare centers in China. Methods A sample of 43 participants were participated in face-to-face, in-depth, semi-structured interviews. Consolidated Framework for Implementation Research was used to identify facilitators and barriers to implementing physician-pharmacist collaborative clinics for diabetes management in primary healthcare centers, and to explore discriminating factors between low and high implementation units. A sustainable strategy repository based on dynamic sustainability framework was established to inform further implementation. Results This study demonstrated that clear recognition of intervention benefits, urgent needs of patients, adaptive and tailored plan, highly collaborative teamwork and leadership support were the major facilitators, while the major barriers included process complexity, large number and poor health literacy of patients in primary areas, inappropriate staffing arrangements, weak financial incentives and inadequate staff competencies. Six constructs were identified to distinguish between high and low implementation units. Sixteen strategies were developed to foster the implementation of physician-pharmacist collaborative clinics, targeting Intervention, Practice setting, and Ecological system. Conclusion This qualitative study demonstrated facilitators and barriers to implementing physician-pharmacist collaborative clinics for diabetes management in primary healthcare centers and developed theory-based strategies for further promotion, which has the potential to improve the management of diabetes and other chronic diseases in under-resourced areas.

Abstract Background Transforming growth factor-β (TGF-β) is a cytokine with multiple functions, including cell growth regulation, extracellular matrix production, angiogenesis homeostasis adjustment and et al. TGF-β pathway activation promotes tumor metastasis/progression and mediates epithelial-mesenchymal transmission suppressing immunosurveillance in advanced tumors. GFH018, a small molecule inhibitor blocking TGF-β signal transduction, inhibits the progression and/or metastasis of advanced cancers. This first-in-human study evaluated the safety, tolerability, pharmacokinetics (PK), and efficacy of GFH018 monotherapy in patients with advanced solid tumors. Methods This phase I, open-label, multicenter study used a modified 3+3 dose escalation and expansion design. Adult patients with advanced solid tumors failing the standard of care were enrolled. Starting at 5 mg, eight dose levels up to 85 mg were evaluated. Patients received GFH018 BID (14d-on/14d-off) starting on the 4th day after a single dose on cycle 1, day 1. Subsequent cycles were defined as 28 days. The study also explored the safety of 85 mg BID 7d-on/7d-off. Adverse events were graded using NCI criteria for adverse events (NCI-CTCAE v5.0). PK was analyzed using a noncompartmental method. Efficacy was evaluated using RECIST 1.1. Blood samples were collected for biomarker analysis. Results Fifty patients were enrolled and received at least one dose of GFH018. No dose-limiting toxicity occurred, and the maximum tolerated dose was not reached. Forty-three patients (86.0%) had at least one treatment-related adverse event (TRAE), and three patients (6.0%) had ≥ G3 TRAEs. The most common TRAEs (any grade/grade ≥3) were AST increased (18%/0%), proteinuria (14%/2%), anemia (14%/2%), and ALT increased (12%/0%). No significant cardiotoxicity or bleeding was observed. GFH018 PK was linear and dose-independent, with a mean half-life of 2.25–8.60 h from 5 – 85 mg. Nine patients (18.0%) achieved stable disease, and one patient with thymic carcinoma achieved tumor shrinkage, with the maximum target lesion decreased by 18.4%. Serum TGF-β1 levels were not associated with clinical responses. The comprehensive recommended dose for Phase II was defined as 85 mg BID 14d-on/14d-off. Conclusions GFH018 monotherapy presented a favorable safety profile without cardiac toxicity or bleeding. Modest efficacy warrants further studies, including combination strategies. Trial registration ClinicalTrial. gov ( https://www.clinicaltrials.gov/ ), NCT05051241. Registered on 2021-09-02.

Abstract Background The rapid global spread of COVID-19 has seriously impacted people’s daily lives and the social economy while also posing a threat to their lives. The analysis of infectious disease transmission is of significant importance for the rational allocation of epidemic prevention and control resources, the management of public health emergencies, and the improvement of future public health systems. Methods We propose a spatiotemporal COVID-19 transmission model with a neighborhood as an agent unit and an urban spatial network with long and short edge connections. The spreading model includes a network of defined agent attributes, transformation rules, and social relations and a small world network representing agents’ social relations. Parameters for each stage are fitted by the Runge-Kutta method combined with the SEIR model. Using the NetLogo development platform, accurate dynamic simulations of the spatial and temporal evolution of the early epidemic were achieved. Results Experimental results demonstrate that the fitted curves from the four stages agree with actual data, with only a 12.27% difference between the average number of infected agents and the actual number of infected agents after simulating 1 hundred times. Additionally, the model simulates and compares different “city closure” scenarios. The results showed that implementing a ‘lockdown’ 10 days earlier would lead to the peak number of infections occurring 7 days earlier than in the normal scenario, with a reduction of 40.35% in the total number of infections. Discussion Our methodology emphasizes the crucial role of timely epidemic interventions in curbing the spread of infectious diseases, notably in the predictive assessment and evaluation of lockdown strategies. Furthermore, this approach adeptly forecasts the influence of varying intervention timings on peak infection rates and total case numbers, accurately reflecting real-world virus transmission patterns. This highlights the importance of proactive measures in diminishing epidemic impacts. It furnishes a robust framework, empowering policymakers to refine epidemic response strategies based on a synthesis of predictive modeling and empirical data.

Aims: The functional traits of twigs and leaves are closely related to the ability of plants to cope with heterogeneous environments. The analysis of the characteristics of twigs and leaves and leaf thermal dissipation in riparian plants is of great significance for exploring the light energy allocation and ecological adaptation strategies of plant leaves in heterogeneous habitats. However, there are few studies on the correlation between the twig–leaf characteristics of riparian plants and their heat dissipation in light heterogeneous environments. Methods: In this study, the riparian plant Hippophae rhamnoides in Taohe National Wetland Park was the research object. According to the differences in the canopy light environment of the H. rhamnoides population, three habitat gradients were set: I, the full sight zone; II, the moderate shade zone; and III, the canopy cover zone. We studied the relationship between the twig–leaf characteristics of H. rhamnoides and leaf thermal dissipation in a heterogeneous light environment. Important Findings: The results are as follows: from the full sight zone to the canopy cover zone, the population characteristics and the twig, leaf, and photosynthetic fluorescence physiological characteristics of H. rhamnoides demonstrated significant changes (p < 0.05). In the full sight zone, H. rhamnoides tended to have thick leaves with a smaller SLA on short and thick twigs, and the light energy absorbed by the leaves accounted for a higher proportion of thermal dissipation. In the moderate shade zone, H. rhamnoides tended to grow many thin leaves with high SLA on long and thick twigs, and the proportion of light energy absorbed by the leaves for heat dissipation was lower than that in the full sight zone. In the canopy cover zone, H. rhamnoides tended to grow a few large and thick leaves with a low SLA on slender and long twigs, and the proportion of light energy absorbed by the leaves for heat dissipation was the lowest. There was a significant correlation between the twig–leaf and leaf heat dissipation of H. rhamnoides in the three habitats (p < 0.05). The co-variation of plant branches and leaves and the timely adjustment of thermal dissipation in photoheterogeneous habitats reflect the phenotypic plasticity mechanism and self-protection strategy of riparian plants in adapting to heterogeneous environments.

As a graphene-like material, h-BN has stimulated great research interest recently due to its potential application for next-generation electronic devices. Herein, a systematic theoretical investigation of electronic structures and optical properties of C-doped and Cu-Al co-doped h-BN is carried out by the first-principles calculations. Firstly, two different C-doped h-BN structures for the para-position and ortho-position are constructed. The results show that the C ortho-doped h-BN (BCN) structure with a band gap of 3.05 eV is relatively stable, which is selected as a substate to achieve the Cu-Al co-doped h-BN. Based on this, the effect of the concentration of C atom doping on the electronic and optical properties of Cu-Al co-doped BCxN (x = 0, 11.1% and 22.2%) is investigated. The results demonstrate that the band gap of Cu-Al co-doped BCxN decreases and the optical properties improve with the increase in C atom concentration. The band gap and static dielectric constant of Cu-Al co-doped BC0N, BC1N and BC2N are 0.98 eV, 0.87 eV and 0.23 eV and 2.34, 3.03 and 3.77, respectively. As for all Cu-Al co-doped BCxN systems, the adsorption peak is red-shifted, and the peak intensity obviously decreases compared to the undoped h-BN. Additionally, the Cu-Al co-doped BC2N exhibits the best response to visible light. This work will provide valuable guidance for designing and developing h-BN-based doping systems with good performance in the field of optical and photocatalysis.

The widespread integration of wind turbines poses voltage stability challenges to power systems. To enhance the ability of wind power systems to actively support grid voltage, grid-forming control techniques are increasingly being employed. However, current research primarily focuses on voltage stability challenges at the point of common coupling in wind power systems, lacking thorough investigation into system voltage response characterization. This paper establishes the voltage response model of a grid-forming wind power system. Based on this model, mathematical derivation and theoretical analysis are conducted, and the effect factors of the voltage at the point of common coupling are investigated. Furthermore, a voltage stabilization method is explored by adjusting the above effect factors. Finally, based on the MATLAB/Simulink platform, the simulation verification of each effect factor is carried out. The results indicate that voltage response characterization obtained by the theoretical analysis and simulation is similar and that the proposed method is valid.

Light-flavor Baijiu (LFB) fermentation is a representative spontaneous mixed-culture solid-state fermentation process in which sorghum is used as the raw material. Raw materials and microorganisms are crucial to the flavor formation and quality of LFB. However, the microbial and physicochemical dynamics of different sorghum varieties during LFB fermentation, as well as their impact on flavor compounds are still largely unknown. Herein, PacBio single-molecule real-time (SMRT) sequencing and headspace solid-phase microextraction coupled with gas chromatography–mass spectrometry (HS-SPME-GC–MS) were applied to investigate microbial community succession and volatile flavor formation in glutinous/non-glutinous sorghum-based fermented grains during LFB fermentation. Fermented grains made of glutinous sorghum Liangnuo No. 1 (GLN) had higher bacterial α-diversity and lower fungal α-diversity than those with fermented grains prepared with non-glutinous red sorghum (NRS) (p

A grid-forming wind generation system exhibits exceptional grid frequency support abilities. The DC capacitor of the grid-forming wind generation system, which is characterized by rapid response and high sensitivity to minor disturbances, can provide short-term inertia support for the power system. This paper proposes the capacitor virtual inertia control for the grid-forming wind generation system, coupling the DC capacitor voltage with the power system frequency, which enables the DC capacitor to participate in the system frequency response process and reduces the rate of change of the system frequency during the disturbance. To analyze the inertia of the wind power generation system, this paper establishes an equivalent Philips–Heffron model for the grid-forming wind generation system and uses the equivalent inertia constant to quantify the inertia of the wind power generation system. The effectiveness of the proposed control strategy and the reasonableness of the inertia assessment method are verified through simulations in the single-turbine system and the IEEE four-machine two-area system.

Background and objectiveNeuroinflammatory processes have been identified as playing a crucial role in the pathophysiology of various neurodegenerative diseases, including idiopathic normal-pressure hydrocephalus (iNPH). iNPH, defined as a common disease of cognitive impairment in older adults, poses major challenges for therapeutic interventions owing to the stringent methodological requirements of relevant studies, clinical heterogeneity, unclear etiology, and uncertain diagnostic criteria. This study aims to assess the relationship between circulating inflammatory biomarkers and iNPH risk using bidirectional two-sample Mendelian randomization (MR) combined with meta-analysis.MethodsIn our bidirectional MR study, genetic data from a genome-wide association study (GWAS) involving 1,456 iNPH cases and 409,726 controls of European ancestry were employed. Single-nucleotide polymorphisms (SNPs) associated with exposures served as instrumental variables for estimating the causal relationships between iNPH and 132 types of circulating inflammatory biomarkers from corresponding GWAS data. Causal associations were primarily examined using the inverse variance-weighted method, supplemented by MR-Egger, weighted median, simple mode, and weighted mode analyses. In the results, heterogeneity was assessed using the Cochran Q test. Horizontal pleiotropy was evaluated through the MR-Egger intercept test and the MR pleiotropy residual sum and outliers test. Sensitivity analysis was conducted through leave-one-out analysis. Reverse MR analyses were performed to mitigate bias from reverse causality. Meta-analyses of identical inflammatory biomarkers from both data sources strengthened the findings.ResultsResults indicated a genetically predicted association between Interleukin-16 (IL-16) [OR: 1.228, 95% CI: 1.049–1.439, p = 0.011], TNF-related apoptosis ligand (TRAIL) [OR: 1.111, 95% CI: 1.019–1.210, p = 0.017] and Urokinase-type plasminogen activator (uPA) [OR: 1.303, 95% CI: 1.025–1.658, p = 0.031] and the risk of iNPH. Additionally, changes in human Glial cell line-derived neurotrophic factor (hGDNF) [OR: 1.044, 95% CI: 1.006–1.084, p = 0.023], Matrix metalloproteinase-1 (MMP-1) [OR: 1.058, 95% CI: 1.020, 1.098, p = 0.003] and Interleukin-12p70 (IL-12p70) [OR: 0.897, 95% CI: 0.946–0.997, p = 0.037] levels were identified as possible consequences of iNPH.ConclusionOur MR study of inflammatory biomarkers and iNPH, indicated that IL-16, TRAIL, and uPA contribute to iNPH pathogenesis. Furthermore, iNPH may influence the expression of hGDNF, MMP-1, and IL-12p70. Therefore, targeting specific inflammatory biomarkers could be promising strategy for future iNPH treatment and prevention.

Abstract Background Kabuki syndrome (KS) is a monogenic disorder leading to special facial features, mental retardation, and multiple system malformations. Lysine demethylase 6A, (KDM6A, MIM*300128) is the pathogenic gene of Kabuki syndrome type 2 (KS2, MIM#300867), which accounts for only 5%–8% of KS. Previous studies suggested that female patients with KS2 may have a milder phenotype. Method We summarized the phenotype and genotype of KS2 patients who were diagnosed in Shanghai Children’s Medical Center since July 2017 and conducted a 1:3 matched case–control study according to age and sex to investigate sex-specific differences between patients with and without KS2. Results There were 12 KS2 cases in this study, and 8 of them matched with 24 controls. The intelligence quotient (IQ) score of the case group was significantly lower than that of the control group (P

Abstract Background Low-level viremia (LLV) has been identified as a potential precursor to virologic failure (VF), yet its clinical implications, particularly within the context of Integrase Strand Transfer Inhibitors (INSTIs)-based regimens, remain insufficiently explored. The study aimed to investigate the relationship between LLV and VF within ART-naïve patients on INSTIs-based regimens in China. Methods A longitudinal cohort study was conducted with ART-naïve patients aged ≥ 18 years at Beijing Ditan Hospital, under the Chinese National Free Antiretroviral Treatment Program (NFATP). The LLV was defined as a viral load (VL) ranging from 50 to 199 copies/mL after six months of ART initiation, and VF as a VL ≥ 200 copies/mL. Sensitive analyses were also performed, defining LLV as 50–999 copies/mL and VF as exceeding 1000 copies/mL. Multivariate logistic regression, Kaplan-Meier (KM) curve, and Generalized Estimating Equation (GEE) models were used to evaluate the risk factors associated with LLV and VF events. Results The study involved 830 ART-naïve patients, comprising 600 in the INSTIs group and 230 in the protease inhibitors (PIs) group. LLV events were observed in 10.4% of patients on PIs-based regimens and and 3.2% on INSTIs-based regimens (P

To avoid the secondary frequency dip caused by the steep drop of the electrical power of wind turbines (WTs) at the end of frequency support stage, the torque limit-based iner-tial control (TLIC) method sets the power reference as a linear function of rotor speed, rather than the step form for the step-wise inertial control. However, the compensation effect on the frequency nadir (FN) caused by the load surge is weakened as the TLIC power is no longer in the step form. Specifically, the maximum point of the frequency response component (FRC) contributed by TLIC occurs earlier than the minimum point of FRC corresponding to the load surge, so that the FN cannot be adequately raised. Therefore, this paper first investigates the relation between the peak and nadir times of FRCs stimulated by the TLIC and load power. On this basis, with the compensation principle of matching the peak and nadir times of FRCs, the improved TLIC method based on delayed support is proposed. Finally, the effectiveness of the proposed method is validated via the experiments on the test bench of wind-integrated power system.

A novel self-adaptive denoising method utilizing optimized empirical wavelet transform (EWT) is proposed to enhance the sensitivity of partial discharge (PD) fluorescence fiber sensors. The optimized EWT enhances the spectrum segmentation capability of conventional EWT via spectral kurtosis (SK). The SK at the optimal window length of noisy PD fluorescence signal is calculated to determine compact support of the Fourier spectrum for subsequent signal decomposition. Frequency components with SK value over the statistic threshold are used to rebuild the PD fluorescence signal. Subsequently, residual noise in the reconstructed signal is removed through adaptive wavelet threshold denoising. To evaluate the performance of the proposed method in denoising numerically simulated and experimentally obtained noisy PD fluorescence signals, outcomes are compared to those of the novel adaptive ensemble empirical mode decomposition (NAEEMD) method, EWT method, EWT joint with kurtogram (KEWT) method, and correlation spectral negentropy (CSNE)-based method. Quantitative metrics and running time are used to assess denoising performance and execution efficiency, respectively. Simulated and experimental results demonstrate that the proposed method possesses a superior noise reduction effect compared to the other four methods while restoring the detail of the PD fluorescence signal flooded by serious noise and consuming reduced computational cost.

With the rapid development of digital intelligence, drones can provide many conveniences for people’s lives, especially in executing rescue missions in special areas. When executing rescue missions in remote areas, communication cannot be fully covered. Therefore, to improve the online adaptability of the task chain link in task planning with a complex system structure as the background, a distributed source-task-capability allocation (DSTCA) problem was constructed. The first task chain coordination mechanism scheme was proposed, and a DSTCA architecture based on the task chain coordination mechanism was constructed to achieve the online adaptability of the swarm. At the same time, the existing algorithms cannot achieve this idea, and the DSTCA-CBBA algorithm based on CNP is proposed. The efficiency change, agent score, and time three indicators are evaluated through specific cases. In response to sudden changes in nodes in the task chain link, the maximum spanning tree algorithm is used to reconstruct the task chain link in a short time, thereby completing the mission task assigned to the drone entity. Meanwhile, the experimental results also prove the effectiveness of the proposed algorithm.

Abstract Background Enhancers play a crucial role in gene regulation, and some active enhancers produce noncoding RNAs known as enhancer RNAs (eRNAs) bi-directionally. The most commonly used method for detecting eRNAs is CAGE-seq, but the instability of eRNAs in vivo leads to data noise in sequencing results. Unfortunately, there is currently a lack of research focused on the noise inherent in CAGE-seq data, and few approaches have been developed for predicting eRNAs. Bridging this gap and developing widely applicable eRNA prediction models is of utmost importance. Results In this study, we proposed a method to reduce false positives in the identification of eRNAs by adjusting the statistical distribution of expression levels. We also developed eRNA prediction models using joint gene expressions, DNA methylation, and histone modification. These models achieved impressive performance with an AUC value of approximately 0.95 for intra-cell prediction and 0.9 for cross-cell prediction. Conclusions Our method effectively attenuates the noise generated by stochastic RNA production, resulting in more accurate detection of eRNAs. Furthermore, our eRNA prediction model exhibited significant accuracy in both intra-cell and cross-cell validation, highlighting its robustness and potential application in various cellular contexts.

Caries is considered to be the most prevalent non-communicable disease in humans, mainly deriving from acidogenic bacterial biofilm and resulting in the demineralization and decomposition of hard dental tissue. Herein, a composite responsive foam brace loaded with magnesium organic framework (MPC) is designed for caries prevention and tooth remineralization. MPC can intelligently release organic antibacterial molecules (gallic acid) and mineralized ions (Mg2+, Ca2+ and PO43−) under acidic conditions (pH

Objective To analyze differences in the indicator framework of the Global Health Security Index (GHSI) and the scores of GHSI indicators for 195 contracting countries of International Health Regulations 2005 (IHR2005) between 2019 and 2021. Methods Yearly GHSI evaluation reports and the data on 195 contracting countries of IHR2005 on GHSI indicator scores for years of 2019 and 2021 were downloaded from official GHSI website (https://www.ghsindex.org) and changes in GHSI indicator framework and contracting country-specific scores of GHSI indicators were analyzed. Paired T-test was used to compare between-year differences in and correlations of country-specific scores of GHSI indicators. General linear regression was adopted to assess the collinearities and correlations between total score and scores of primary/secondary indicators of GHSI for 195 contracting countries of IHR2005 in 2021. ResultsIn 2021, the average GHSI score was 38.9 (in a scale with 5 categories and the maximum score of 100) for the 195 contracting countries of IHR2005 nearly the same as that (40.2) of 2019; none of the 195 contracting countries was assessed as having the GHSI score of the optimum grade (the scores of > 80) and 66.7% of the countries were scored below 40, with a median score of 34.9. Compared to that of 2019, the GSHI 2021 index framework was supplemented with 3 secondary indicators, 11 tertiary indicators, and 31 questions. The results of paired T-test showed that the average score of GHSI for the 195 contracting countries in 2021 was increased by 0.1 point against that of 2019, but the difference was not statistically significant (P > 0.05). In comparison with those in 2019, following average scores decreased significantly for primary indicators of preventing the emergence or spread of pathogens (reduced by 0.6, t = – 2.413; P < 0.05) and rapidly responding to/reducing disease transmission (by 4.0, t = – 9.402; P < 0.05), secondary indicators of zoonosis prevention (by 4.8, t = – 6.590; P < 0.001) and trade and travel restrictions (by 58.3, t = – 33.158; P < 0.001). There were strong correlations between country-specific scores of secondary indicators of 2019 and those of 2021, except for the score of trade and travel restrictions (r = 0.117) and the score of implementing response plan (r = 0.237) . General linear regression analysis showed that there was no collinearity among the country-specific scores of 6 primary indicators in 2021, but the total scores of all indicators were significantly correlated with the scores of 6 primary indicators (P < 0.05 for all). Conclusion Based on the assessment using GHSI scores, none of the 195 IHR2005 contracting countries is well prepared for the next probable disease pandemic and the ability to prevent and respond to public health emergencies needs to be improved for the countries.

Abstract Background Abnormally regulated long non-coding RNAs (lncRNAs) functions in cancer emphasize their potential to serve as potential targets for cancer therapeutic intervention. LncRNA ASBEL has been identified as oncogene and an anti-sense transcript of tumor-suppressor gene of BTG3 in triple-negative breast cancer (TNBC). Results Herein, multicomponent self-assembled polyelectrolyte nanocomplexes (CANPs) based on the polyelectrolytes of bioactive hyaluronic acid (HA) and chitosan hydrochloride (CS) were designed and prepared for the collaborative modulation of oncogenic lncRNA ASBEL with antago3, an oligonucleotide antagonist targeting lncRNA ASBEL and hydrophobic curcumin (Cur) co-delivery for synergetic TNBC therapy. Antago3 and Cur co-incorporated CANPs were achieved via a one-step assembling strategy with the cooperation of noncovalent electrostatic interactions, hydrogen-bonding, and hydrophobic interactions. Moreover, the multicomponent assembled CANPs were ulteriorly decorated with a near-infrared fluorescence (NIRF) Cy-5.5 dye (FCANPs) for synchronous NIRF imaging and therapy monitoring performance. Resultantly, MDA-MB-231 cells proliferation, migration, and invasion were efficiently inhibited, and the highest apoptosis ratio was induced by FCANPs with coordination patterns. At the molecular level, effective regulation of lncRNA ASBEL/BTG3 and synchronous regulation of Bcl-2 and c-Met pathways could be observed. Conclusion As expected, systemic administration of FCANPs resulted in targeted and preferential accumulation of near-infrared fluorescence signal and Cur in the tumor tissue. More attractively, systemic FCANPs-mediated collaborative modulating lncRNA ASBEL/BTG3 and Cur co-delivery significantly suppressed the MDA-MB-231 xenograft tumor growth, inhibited metastasis and extended survival rate with negligible systemic toxicity. Our present study represented an effective approach to developing a promising theranostic platform for combating TNBC in a combined therapy pattern.

Users of the digital image correlation method are faced with the problem of poor operability, low repeatability, and lack of standardized specifications for spraying speckles. To solve the problem, the research proposed a rock deformation measurement method that obviates the need to spray speckles. A local binary model was established by using the local binary pattern (LBP) operator based on deep texture features on rock surfaces. The resulting LBP digital speckle pattern can substitute artificial speckle patterns and demonstrates high quality and strong applicability. Based on the LBP digital speckle pattern, the target tracking algorithm was employed to achieve non-contact measurement of the dynamic displacements of rocks. The feasibility and effectiveness of the algorithm in practical application were verified by conducting shear tests on granite and siltstone. Test results show that the deformation characteristics in the displacement nephograms are in line with the measured data pertaining to rock fracturing and conform to the basic characteristics of the shear failure of rocks. The deformation measurement method based on surface texture information can realize non-contact displacement measurement of rocks under conditions without speckles: this obviates the influence of the quality of sprayed speckles on the accuracy of the measurement of deformation.

Abstract Background Lodging is a major factor contributing to yield loss and constraining the mechanical harvesting of wheat crops. Genetic improvement through breeding effectively reduced the lodging and improved the grain yield, however, the physiological mechanisms involved in providing resistance to lodging are different in the breeding stage and are not clearly understood. The purpose of this study was to compare the differences in the lodging resistance (LR) of the wheat varieties released during the different decades and to explore the effect of the application of nitrogen (N) fertilizer on the plasticity of LR. Results A field study was conducted during the cultivation seasons of 2019–2020 and 2020–2021, in soil supplemented with three N levels: N0 (0 kg ha–1), N180 (200 kg ha–1), and N360 (360 kg ha–1) using eight varieties of wheat released for commercial cultivation from 1950 to date. The results obtained showed that genetic improvement had significantly enhanced the LR and grain yield in wheat. In the first breeding stage (from 1950 to 1980s) the lodging resistant index increased by 15.0%, which was primarily attributed to a reduced plant height and increased contents of cellulose, Si, and Zn. In the second breeding stage (the 1990s–2020s) it increased by 172.8%, which was mainly attributed to an increase in the stem diameter, wall thickness, and the contents of K, Ca, Fe, Mn, and Cu. The application of N fertilizer improved the grain yield but reduced the LR in wheat. This was mainly due to an increase in plant height resulting in an elevation of the plant center of gravity, a decrease in the contents of cellulose, and a reduction in the area of large-sized vascular bundles in the stems, even if N supplementation increased the concentrations of K, Ca, and Si. Conclusion Although breeding strategies improved the stem strength, the trade-off between the grain yield and LR was more significantly influenced by the addition of N. Overcoming this peculiar situation will serve as a breakthrough in improving the seed yield in wheat crops in the future.

Abstract Background Cardio-facio-cutaneous (CFC) syndrome is a RASopathy subtype that presents with unique craniofacial dysmorphology, congenital heart disease, dermatologic abnormalities, growth retardation, and intellectual disability. This study describes the phenotypic spectrum of CFC in China and its association with CFC syndrome gene variants. Results Twenty Chinese CFC patients, aged 0.6–9.5 years old, were included in this study and their clinical phenotypic spectrum was compared with that of 186 patients with CFC from non-Chinese ethnicities. All 20 Chinese patients with CFC carried de novo heterozygous BRAF, MAP2K1, and MAP2K2 variants. Two novel variants were detected and consistently predicted to be deleterious using bioinformatic tools. The clinical features of CFC in the Chinese patients included hypertrophic cardiomyopathy (2/20, 10%), pulmonary valve stenosis (2/20, 10%), curly or sparse hair (7/20, 35%), epilepsy (1/20, 5%), and hypotonia (10/20, 50%); these features were less frequently observed in Chinese patients than non-Chinese patients (p

Abstract Objectives Lung adenocarcinoma (LUAD) exhibits a higher fatality rate among all cancer types worldwide, yet the precise mechanisms underlying its initiation and progression remain unknown. Mounting evidence suggests that long non-coding RNAs (lncRNAs) exert significant regulatory roles in cancer development and progression. Nevertheless, the precise involvement of lncRNA CYP4A22-AS1 in LUAD remains incompletely comprehended. Methods Bioinformatics analyses evaluated the expression level of CYP4A22-AS1 in lung adenocarcinoma and paracancer. The LUAD cell line with a high expression of CYP4A22-AS1 was constructed to evaluate the role of CYP4A22-AS1 in the proliferation and metastasis of LUAD by CCK8, scratch healing, transwell assays, and animal experiments. We applied transcriptome and microRNA sequencing to examine the mechanism of CYP4A22-AS1 enhancing the proliferation and metastasis of LUAD. Luciferase reporter gene analyses, west-blotting, and qRT-PCR were carried out to reveal the interaction between CYP4A22-AS1, miR-205-5p/EREG, and miR-34c-5p/BCL-2 axes. Results CYP4A22-AS1 expression was significantly higher in LUAD tissues than in the adjacent tissues. Furthermore, we constructed a LUAD cell line with a high expression of CYP4A22-AS1 and noted that the high expression of CYP4A22-AS1 significantly enhanced the proliferation and metastasis of LUAD. We applied transcriptome and microRNA sequencing to examine the mechanism of CYP4A22-AS1 enhancing the proliferation and metastasis of LUAD. CYP4A22-AS1 increased the expression of EREG and BCL-2 by reducing the expression of miR-205-5p and miR-34-5p and activating the downstream signaling pathway of EGFR and the anti-apoptotic signaling pathway of BCL-2, thereby triggering the proliferation and metastasis of LUAD. The transfection of miR-205-5p and miR-34-5p mimics inhibited the role of CYP4A22-AS1 in enhancing tumor progression. Conclusion This study elucidates the molecular mechanism whereby CYP4A22-AS1 overexpression promotes LUAD progression through the miR-205-5p/EREG and miR-34c-5p/BCL-2 axes.

ObjectiveTo establish a set of indicators for assessing the public health emergency response capacity at county/district level in China. MethodsAn indicator system for evaluating public health emergency response capacity at county/district level was initially formulated based on theoretical research and literature review. Three rounds of Delphi consultation were conducted among 18 senior professionals to determine the indicators and their weights of the system using hierarchical analysis method. ResultsFor the 3 rounds of expert consultation, the positive coefficients of the were 100.0%, 88.9%, and 88.9%; the expert authority coefficients were 0.87, 0.84, and 0.87; and the coordination coefficients of expert opinions were 0.207, 0.210, and 0.295 (all P < 0.001), indicating a good coordination of the experts′ opinions. The finally established indicator system for assessing public health emergency response capacity at county/district level included 5 first-, 19 second-, and 61 third-level indicators. For the third round of Delphi consultation, the experts′ mean scores and ranges of coefficients of variance for importance/feasibility of all the indicators were 4.83 ± 0.13/4.48 ± 0.21 and 0.00 – 0.18/0.07 – 0.22, respectively. The weights for the first-, second-, and third-level indicators ranged from 0.094 to 0.290, 0.011 to 0.119, and 0.001 to 0.087, respectively. ConclusionThe established indicator system could be used to develop tools for evaluating public health emergency response capacities at county/district level, while the reliability and validity of the indicator system need to be assessed further.

Based on the rockery photos of 10 classical gardens including world cultural heritage, this paper incorporates the combined analysis and comparison of constituent elements (rockeries, buildings and plants) of scenic surfaces, and probes into the fractal characteristics of landscaping through the theory and the fractal dimension (FD) value analysis software. Studies have shown that the quantitative evaluation data of visual complexity (FD, i.e., fractal dimension) can characterize the contour morphology of constituent elements of the scenic surface of rockeries. The relevant analysis results are as follows: (1) FD can directly quantify the morphological contour of each element. Through the statistical analysis, it can effectively avoid the misjudgment of empirical cognition and subjective feeling. Therefore, FD value can be used as one of the effective indexes to evaluate the complexity and diversity of rockery and landscape elements. (2) The change in the level of the FD value enables the intuitive analysis of the effects of the plant varieties and landscaping techniques on rockery morphological complexity. (3) Higher FD value is not always better. Necessary morphological maintenance is required to avoid excessive FD value of plants.

ABSTRACTSpecies delimitation based on lineage definition has become increasingly popular. However, these methods have been limited, especially for species that lack genomic data and are morphologically similar. The trickiest part for the species identification is that the interspecific and intraspecific boundaries are vague. Taking Prorocentrum (Dinophyta) as an example, analysis of cell morphology, growth, and toxin synthesis in both species of P. lima and P. arenarium does not provide a reliable basis for species delineation. However, through phylogenetic and genetic distance analyses of their ITS and LSU sequences, establishment of evolutionary tree based on orthologous gene sequences, and combining the results of automatic barcode gap discovery and Poisson tree processes models, it was sustained that P. arenarium does not belong to the P. lima complex and should be considered as an independent species. Interspecies genetic evolution analysis revealed that P. lima and P. arenarium may contribute to evolutionary direction that favors combating reverse environmental factors. In P. lima, viral invasion may be one of the reasons for its large genome size. In the study, P. lima complex has been selected as an example to enhance the taxonomic identification of microalgae through molecular and genetic evolution, offering valuable insights into refining taxonomic identification and promoting microbial biodiversity research in other species.IMPORTANCEMicroalgae, especially the species known as Prorocentrum, have received significant attention due to their ability to trigger harmful algal blooms and produce toxins. However, the boundaries between species and within species are ambiguous. Clear and comprehensive species delineation indicates that Prorocentrum arenarium should be considered as an independent species, separate from the Prorocentrum lima complex. Improving the classification and identification of microalgae through molecular and genetic evolution will provide reference points for other cryptic species. Prorocentrum occupy multiple ecological niches in marine environments, and studying their evolutionary direction contributes to understanding their ecological adaptations and community succession.