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Abstract Oral squamous cell carcinoma (OSCC) is a common malignant tumor in the head and neck, associated with high recurrence and poor prognosis. We performed an integrated analysis of single-cell RNA and spatial transcriptomic data from cancerous and normal tissues to create a comprehensive atlas of epithelial cells and cancer-associated fibroblasts (CAFs). Our findings show that AKR1C3+ epithelial cells, located at the tumor’s stromal front, exhibit significant copy number variation and poor prognostic indicators, suggesting a role in tumor invasion. We also identified a distinct group of early-stage CAFs (named OSCC_Normal, characterized by ADH1B+, MFAP4+, and PLA2G2A+) that interact with AKR1C3+ cells, where OSCC_Normal may inhibit the FOXO1 redox switch in these epithelial cells via the IGF1/IGF1R pathway, causing oxidative stress overload. Conversely, AKR1C3+ cells use ITGA6/ITGB4 receptor to counteract the effects of OSCC_Normal, promoting cancer invasion. This study unveils complex interactions within the OSCC tumor microenvironment.

Abstract Patch features obtained by fixed convolution kernel have become the main form in hyperspectral image (HSI) classification processing. However, the fixed convolution kernel limits the weight learning of channels, which results in the potential connections between pixels not being captured in patches, and seriously affects the classification performance. To tackle the above issues, we propose a novel Adaptive Pixel Attention Network, which can improve HSI classification by further mining the connections between pixels in patch features. Specifically, a Spectral–Spatial Superposition Enhancement module is first proposed for enhancing the spectral–spatial information of 3D input cubes via complementing the 1D spectral vectors by zero and reflection filling operations. More importantly, we also propose a new Adaptive Pixel Attention mechanism, which explores Cosine and Euclidean similarity to adaptively explore the distance and angle relationship between pixels of different scale convolution patch features. Moreover, the Cross-Layer Information Complement module is designed to form a contextual interaction by integrating the output features of different convolution layers, which can prevent the omission of discriminative information and further improve the network performance. Experimental results on four widely used HSI datasets IP, UP, HU, and KSC show that the proposed network is superior to other state-of-the-art classification models in accuracy, and it also has a better efficiency than other 3D works.

Abstract Continuous and long-term therapeutic monitoring of medicine molecules in biological systems will revolutionize healthcare by offering personalized pharmacokinetic reports. However, the extremely complex biological environment brings great challenges for in vivo molecule detection in living organisms. Here we introduce an in vivo photoelectrochemical biosensor following a reverse design strategy with single atoms as molecular recognition units. Atomic dispersion of Cu single atoms on TiO2-x substrate create synergistic anchoring triple-site for efficiently and selectively capturing of dual-carbonyl group and neighboring dual-hydroxyl group of tetracycline molecules. The photoelectrode is encapsulated with antibiofouling layer and implanted into the vein of living mouse to enable long-term in vivo monitoring of tetracycline in real biological environments. It is important to note that our approach was exclusively tested in male mice, and therefore, the findings may not be generalizable to female mice or other species without further research. The rationally designed biological-components-free in vivo biosensor with excellent selectivity, robustness, and stability endows possibility for enabling personalized medicine guidance through real-time feedbacking information and providing direct and authentic medicine molecular analysis.

Abstract Background Vitamin D was shown to directly exert a protective effect on diabetic kidney disease (DKD) in our previous study. However, whether it has an effect on perirenal adipose tissue (PRAT) or the intestinal flora and its metabolites (trimethylamine N-oxide, TMAO) is unclear. Methods DKD mice were received different concentrations of 1,25-(OH)2D3 for 2 weeks. Serum TNF-α levels and TMAO levels were detected. 16S rRNA sequencing was used to analyze gut microbiota. qPCR was used to detect the expression of TLR4, NF-Κb, PGC1α, and UCP-1 in kidney and adipose tissue. Histological changes in kidney and perirenal adipose tissue were observed using HE, PAS, Masson and oil red staining. Immunofluorescence and immunohistochemistry were used to detect the expression of VDR, PGC1α, podocin, and UCP-1 in kidney and adipose tissue. Electron microscopy was used to observe the pathological changes in the kidney. VDR knockout mice were constructed to observe the changes in the gut and adipose tissue, and immunofluorescence and immunohistochemistry were used to detect the expression of UCP-1 and collagen IV in the kidney. Results 1,25-(OH)2D3 could improve the dysbiosis of the intestinal flora of mice with DKD, increase the abundance of beneficial bacteria, decrease the abundance of harmful bacteria, reduce the pathological changes in the kidney, reduce fat infiltration, and downregulate the expression of TLR4 and NF-κB in kidneys. The serum TMAO concentration in mice with DKD was significantly higher than that of the control group, and was significantly positively correlated with the urine ACR. In addition, vitamin D stimulated the expression of the surface markers PGC1α, UCP-1 and VDR in the PRAT in DKD mice, and TMAO downregulated the expression of PRAT and renal VDR. Conclusions The protective effect of 1,25-(OH)2D3 in DKD mice may affect the intestinal flora and its related metabolite TMAO on perirenal fat and kidneys.

Abstract Various types of foreign fibres may be mixed in the planting, transportation, and production processes of cotton, which not only cause equipment to be out of control, but also leads to a decrease in the quality of cotton textile products and economic losses. The machine vision based detection method for cotton foreign fibres is widely used. Based on existing related research, we construct a classification dataset for cotton foreign fibres in practical scenarios, named the CF2113‐10 dataset. The authors design a basic foreign fibre classification network called CottonNet that balances performance and efficiency. The classification accuracy on the validation set reached 94.2%. In order to enhance the high‐level feature extraction ability, this paper improves the feature fusion method of residual networks and proposes CottonNet‐Res, which improves the classification accuracy to 95.1%. Finally, a classification model based on feature difference fitting, CottonNet‐Fusion, is proposed to address the classification problem of foreign fibre images sampled in complex environments. The classification accuracy of foreign fibre images sampled in ordinary scenes has improved to 97.4%, while the images sampled in complex environments maintain an accuracy of 90.3%.

This paper proposes a conceptual framework for integrating Artificial Intelligence (AI) into the curriculum. It builds on previous conceptual papers, which provided initial suggestions on integrating AI into teaching. The approach to developing the conceptual framework includes drawing on existing frameworks, AI literature, and case studies from the Queen Mary University of London President and Principal, an AI literacy-funded project. The opinion piece aims to advance our thinking on creating a teaching and learning toolkit to support educators in integrating AI into their teaching, enhancing students’ AI literacy and skills. This paper has two main objectives: first, it develops an AI literacy conceptual framework to support educators in integrating AI into their teaching, and second, it provides suggestions on how to engage with it.

Parkinson’s disease (PD) is a neurodegenerative disorder that significantly impacts patients’ quality of life. Recent evidence has highlighted a complex relationship between the gut microbiota (GM) and PD. Understanding this relationship is crucial for potentially targeting GM in PD treatment and expanding therapeutic options. This study aimed to comprehensively analyze the global landscape, trends, and research focus on GM and PD using bibliometric analysis. Utilizing publications from the Web of Science Core Collection (WsSCC), bibliometric tools such as the R package ‘Bibliometrix,’ VOS viewer, and CiteSpace software were employed to assess parameters like yearly publications, countries/regions, institutions, and authors. Research trends and hotspots were identified through keyword analysis. The results revealed 1,161 articles published between 2013-2023, with China leading in publications (n=352, 30.31% of total), while the United States had a higher influence (H-index=58). The University of California System was the top institution in terms of publications (n=35), with the National Natural Science Foundation of China funding the most projects (n=172). Keshavarzian A and Sampson TR were the authors with the highest publication and co-citation counts, respectively. The International Journal of Molecular Sciences had the most articles published (n=48). Keyword analysis identified parkinson’s disease, gut microbiota, short-chain fatty acids, inflammation, and probiotics as main research topics. Biomarkers, ketogenic diet, and NF-κB were recent research hotspots and trends (2021-2023). The current study conducts an objective and comprehensive analysis of these publications, identifying trends and hotspots in the field of research. The findings offer valuable insights to scholars globally and in-vestigate potential therapeutic strategies for Parkinson’s Disease.

Abstract In engineered photonic lattices, topological photonic (TP) modes present a promising avenue for designing waveguides with suppressed backscattering. However, the integration of the TP modes in electromagnetic systems has faced longstanding challenges. The primary obstacle is the insufficient development of high‐efficiency coupling technologies between the TP modes and the conventional transmission modes. This dilemma leads to significant scattering at waveguide terminals when attempting to connect the TP waveguides with other waveguides. In this study, a topological photonic substrate‐integrated waveguide (TPSIW) is proposed that can seamlessly integrate into traditional microstrip line systems. It successfully addresses the matching problem and demonstrates efficient coupling of both even and odd TP modes with the quasi‐transverse electromagnetic modes of microstrip lines, resulting in minimal energy losses. In addition, topological leaky states are introduced through designed slots on the TPSIW top surface. These slots enable the creation of TP leaky‐wave antennas with beam steering capabilities. A wireless link based on TPSIWs are further established that enables the transmission of distinct signals toward different directions. This work is an important step toward the integration of TP modes in microwave systems, unlocking the possibilities for the development of high‐performance wireless devices.

BackgroundTryptophan Metabolism-associated Genes (TMGs), such as ECHS1 and ALDH2, are crucial in cancer progression through immunosuppressive mechanisms, particularly in Gastric Cancer (GC). This study explores their effects on the Tumor Microenvironment (TME). Additionally, it examines their potential as novel immunotherapy targets.MethodsWe utilized single-cell and bulk transcriptomic technologies to analyze the heterogeneity of GC. Non-negative Matrix Factorization (NMF) clustering identified key TMGs, and extensive RNA-seq analyses were performed to pinpoint prognostic genes and potential immunotherapy targets. Furthermore, through PCR analyses we found that ECHS1 and ALDH2 gene expression plays a regulatory role in the migration, invasion and inflammatory factor in AGS and SNU-1 cell lines. The interference effect of si-ECHS1 and ad-ALDH2 was validated using cell scratch assay in AGS and SNU-1 cell line.ResultsWe observed a statistically significant correlation between ECHS1 and ALDH2 expression and increased TME heterogeneity. Our findings also revealed that ECHS1 down-regulation and ALDH2 up-regulation contribute to reduced TME heterogeneity, decreased inflammation, and inhibited AGS and SNU-1 tumor cells migration and proliferation. GSVA enrichment analysis highlighted the NF-kappa B(NF-κB) signaling pathway as specifically regulated by TMGs. Furthermore,ECHS1 and ALDH2 modulated CD8+ and CD4+ T cell activities, impacting GC progression. In vitro experiments further solidified our conclusions by showcasing the inhibitory effects of Si-ECHS1 and ad-ALDH2 on the invasive and proliferative capabilities of AGS and SNU-1 cells. Moreover, Si-ECHS1 and ad-ALDH2 gene expression effectively reduced the expression of inflammatory factors IL-10,IL-7,CXCL8 and IL-6, leading to a remarkable alleviation of chronic inflammation and the heterogeneous nature of the TME.ConclusionThis research highlights the importance of ECHS1 and ALDH2 in GC progression and immune modulation, suggesting that targeted therapies focusing on these genes offer promising avenues for personalized immunotherapy in GC. These findings hold potential for improving patient survival and quality of life. Future studies on the NF-κB signaling pathway’s role in this context are warranted to further elucidate the mechanisms underlying TMG-mediated immune modulation in GC.

Arsenic is a widespread carcinogen and an important etiological factor for lung cancer. Dysregulated miRNAs have been implicated in arsenic carcinogenesis and the mechanisms of arsenic-induced dysregulated miRNAs have not been fully elucidated. N6-methyladenosine (m6A) modification is known to modulate pri-miRNA processing. However, whether m6A-mediated pri-miRNA processing is involved in arsenic carcinogenesis is poorly understood. Here, we found that m6A modification was significantly increased in arsenite-transformed human bronchial epithelial BEAS-2B cells (0.5 µM arsenite, 16 weeks). Meanwhile, METTL3 was significantly upregulated at week 12 and 16 during cell transformation. The proliferation, migration, invasion, and anchorage-independent growth of arsenite-transformed cells were inhibited by the reduction of m6A levels through METTL3 knockdown. Further experiments suggest that the oncogene miR-106b-5p is a potentially essential m6A target mediating arsenic-induced lung cancer. miR-106b-5p was observed to be upregulated after exposure to arsenite for 12 and 16 weeks, and the reduction of m6A levels caused by METTL3 knockdown inhibited miR-106b-5p maturation in arsenite-transformed cells. What’s more, miR-106b-5p overexpression successfully rescued METTL3 knockdown-induced inhibition of the neoplastic phenotypes of transformed cells. Additionally, Basonuclin 2 (BNC2) was uncovered as a potential target of miR-106b-5p and downregulated by METTL3 via enhancing miR-106b-5p maturation. Additionally, the METTL3 inhibitor STM2457 suppressed neoplastic phenotypes of arsenite-transformed BEAS-2B cells by blocking pri-miR-106b methylation. These results demonstrate that m6A modification promotes the neoplastic phenotypes of arsenite-transformed BEAS-2B cells through METTL3/miR-106b-5p/BNC2 pathway, providing a new prospective for understanding arsenic carcinogenesis.

The different generations of bearing steel are designed to withstand high temperatures, quick speeds, and heavy loads and meet the requirements of aviation, aerospace, and advanced equipment production. In this study, three generation bearing systems (Si3N4/GCr15, Si3N4/M50, and Si3N4/CSS-42L) with pentaerythritol ester lubricants were selected to investigate their friction behavior and evolutionary mechanisms from room temperature to 350 °C. The results indicate that the coefficient of friction (COF) values for all three systems initially decreased and then increased as the temperature increased. The COF of Si3N4/GCr15 was not more than 0.170 when the temperature did not exceed 150 °C. Furthermore, the wear rate of Si3N4/M50 and Si3N4/CSS-42L are 2.67 × 10−4 mm3·N−1·m−1 and 2.04 × 10−4 mm3·N−1·m−1 at 260 °C, which are only 15.4% and 11.8% of Si3N4/GCr15. This discrepancy can be attributed to the formation of metal oxides on the worn surface of Si3N4/M50 and Si3N4/CSS-42L, and was easier to form on the worn surface of CSS-42L. Therefore, the applicable temperature range for GCr15 usually below 150 °C and for Si3N4/M50 and Si3N4/CSS-42L, it was from 150 to 260 °C. These results disclose the friction behavior and mechanism of these three generation bearing steel are different, and can be a guideline to choose proper bearing steel in future situation.

Background/Aims Four-week treatment of linvencorvir (RO7049389) was generally safe and well tolerated, and showed anti-viral activity in chronic hepatitis B (CHB) patients. This study evaluated the efficacy, safety, and pharmacokinetics of 48-week treatment with linvencorvir plus standard of care (SoC) in CHB patients. Methods This was a multicentre, non-randomized, non-controlled, open-label phase 2 study enrolling three cohorts: nucleos(t)ide analogue (NUC)-suppressed patients received linvencorvir plus NUC (Cohort A, n=32); treatment-naïve patients received linvencorvir plus NUC without (Cohort B, n=10) or with (Cohort C, n=30) pegylated interferon-α (Peg-IFN-α). Treatment duration was 48 weeks, followed by NUC alone for 24 weeks. Results 68 patients completed the study. No patient achieved functional cure (sustained HBsAg loss and unquantifiable HBV DNA). By Week 48, 89% of treatment-naïve patients (10/10 Cohort B; 24/28 Cohort C) reached unquantifiable HBV DNA. Unquantifiable HBV RNA was achieved in 92% of patients with quantifiable baseline HBV RNA (14/15 Cohort A, 8/8 Cohort B, 22/25 Cohort C) at Week 48 along with partially sustained HBV RNA responses in treatment-naïve patients during follow-up period. Pronounced reductions in HBeAg and HBcrAg were observed in treatment-naïve patients, while HBsAg decline was only observed in Cohort C. Most adverse events were grade 1–2, and no linvencorvir-related serious adverse events were reported. Conclusions 48-week linvencorvir plus SoC was generally safe and well tolerated, and resulted in potent HBV DNA and RNA suppression. However, 48-week linvencorvir plus NUC with or without Peg-IFN did not result in the achievement of functional cure in any patient.

Abstract Background This case report documents a case of malignant pheochromocytoma manifested as vision changes with lung metastasis and recurrence. Case presentation A 10-year-old Han Chinese girl presented with vision changes and was eventually diagnosed with pheochromocytoma by contrast-enhanced computed tomography, urine vanillylmandelic acid. After medication for hypertension and surgery, clinical symptoms disappeared. Malignant pheochromocytoma with lung metastasis was confirmed histologically using the Pheochromocytoma of the Adrenal Gland Scaled Score scoring system and genetically with succinate dehydrogenase complex iron sulfur subunit B mutation, and 3 months later, unplanned surgery was performed because of the high risks and signs of recurrence. She is asymptomatic as of the writing of this case report. Our patient’s case highlights the importance of considering a diagnosis of malignant pheochromocytoma, and long-term follow-up for possible recurrence. Conclusion Although there are well-recognized classic clinical manifestations associated with pheochromocytoma, atypical presentation, such as vision changes in children, should be considered. In addition, malignant pheochromocytoma children with a high Pheochromocytoma of the Adrenal Gland Scaled Score and succinate dehydrogenase complex iron sulfur subunit B mutation require a long-term follow-up or even unplanned surgery because of the higher risk of recurrence.

As pivotal structural component, steels operating at high temperatures play a vital role in promoting the development of advanced equipment technology. Enduring and efficient lubricants are critical bottleneck for the construction of high-temperature frictional subsystems. Polydiethylsiloxane oil (PDES) significantly reduces the coefficient of friction (COF) (9.80–16.74 %) and wear rate (28.95–54.59 %) in the Si3N4–8Cr4Mo4V system without sulfur and phosphorus anti-wear additives at 250 °C. With only 1 wt% PDES, there is a remarkable 28.95 % wear rate reduction in the Si3N4–8Cr4Mo4V frictional system. The enhanced lubrication performance come from the Si–O tribofilm at lower PDES concentrations (1–15 wt%). Once exceeding a PDES concentration of 30 wt%, the as-formed Si–O tribofilm transitions to a Fe–Mo compound film, exhibiting superior friction reduction and wear resistance properties.

ObjectedTo evaluate the association between osteoarthritis (OA) and Parkinson’s disease (PD) in adults in the United States.MethodsUsing 2011–2020 NHANES data, a cross-sectional study of 11,117 adults over the age of 40 was conducted. Univariate logistic regression and multivariate logistic regression were used to analyze the relationship between arthritis and PD. In addition, stratified analysis was used to examine whether the relationship between arthritis and PD was interactive with age, gender, race, education, BMI.ResultsIn this study, a total of 11,117 participants were included, and we found that osteoarthritis was positively correlated with the development of PD compared with non-arthritis patients [1.95 (1.44 ~ 2.62)] (p

Compared with 454 sequencing technology, short-read sequencing (e.g., Illumina) technology generates sequences of high accuracy, but limited length (500 bp) is challenging. The ammonia monooxygenase subunit A (amoA) gene of ammonia-oxidizing archaea (AOA), which plays a crucial part in the nitrification process, is such a gene. By providing a full overview of the community of a functional microbial guild, 16S ribosomal ribonucleic acid (rRNA) gene sequencing could overcome this problem. However, it remains unclear how 16S rRNA primer selection influences the quantification of relative abundance and the identification of community composition of nitrifiers, especially AOA. In the present study, a comparison was made between the performance of primer pairs 338F-806R, 515F-806R, and 515F-907R to a shotgun metagenome approach. The structure of nitrifier communities subjected to different long-term organic matter amendment and water management protocols was assessed. Overall, we observed higher Chao1 richness diversity of soil total bacteria by using 515F-806R compared to 338F-806R and 515F-907R, while higher Pielou’s evenness diversity was observed by using 515F-806R and 515F-907R compared to 338F-806R. The studied primer pairs revealed different performances on the relative abundance of Thaumarchaeota, AOB, and NOB. The Thaumarchaeota 16S rRNA sequence was rarely detected using 338F-806R, while the relative abundances of Thaumarchaeota detected using 515F-806R were higher than those detected by using 515F-907R. AOB showed higher proportions in the 338F-806R and 515F-907R data, than in 515F-806R data. Different primers pairs showed significant change in relative proportion of NOB. Nonetheless, we found consistent patterns of the phylotype distribution of nitrifiers in different treatments. Nitrosopumilales (NP) and Nitrososphaerales (NS) clades were the dominant members of the AOA community in soils subject to controlled irrigation, whereas Ca. Nitrosotaleales (NT) and NS clades dominated the AOA community in soils subject to flooding irrigation. Nitrospira lineage II was the dominant NOB phylotype in all samples. Overall, ideal 16S rRNA primer pairs were identified for the analysis of nitrifier communities. Moreover, NP and NT clades of AOA might have distinct environmental adaptation strategies under different irrigation treatments.

Cardiac tissue engineering has emerged as a promising approach for restoring the functionality of damaged cardiac tissues following myocardial infarction. To effectively replicate the native anisotropic structure of cardiac tissues in vitro, this study focused on the fabrication of micropatterned gelatin methacryloyl hydrogels with varying geometric parameters. These substrates were evaluated for their ability to guide induced pluripotent stem cell-derived cardiomyocytes (CMs). The findings demonstrate that the mechanical properties of this hydrogel closely resemble those of native cardiac tissues, and it exhibits high fidelity in micropattern fabrication. Micropatterned hydrogel substrates lead to enhanced organization, maturation, and contraction of CMs. A microgroove with 20-μm-width and 20-μm-spacing was identified as the optimal configuration for maximizing the contact guidance effect, supported by analyses of nuclear orientation and F-actin organization. Furthermore, this specific micropattern design was found to promote CMs' maturation, as evidenced by increased expression of connexin 43 and vinculin, along with extended sarcomere length. It also enhanced CMs' contraction, resulting in larger contractile amplitudes and greater contractile motion anisotropy. In conclusion, these results underscore the significant benefits of optimizing micropatterned gelatin methacryloyl for improving CMs' organization, maturation, and contraction. This valuable insight paves the way for the development of highly organized and functionally mature cardiac tissues in vitro.

Numerous bacterial species employ diffusible signal factor (DSF)-based quorum sensing (QS) as a widely conserved cell–cell signaling communication system to collectively regulate various behaviors crucial for responding to environmental changes. cis-11-Methyl-dodecenoic acid, known as DSF, was first identified as a signaling molecule in Xanthomonas campestris pv. campestris. Subsequently, many structurally related molecules have been identified in different bacterial species. This review aims to provide an overview of current understanding regarding the biosynthesis and regulatory role of DSF signals in both pathogenic bacteria and a biocontrol bacterium. Recent studies have revealed that the DSF-based QS system regulates antimicrobial factor production in a cyclic dimeric GMP-independent manner in the biocontrol bacterium Lysobacter enzymogenes. Additionally, the DSF family signals have been found to be involved in suppressing plant innate immunity. The discovery of these diverse signaling mechanisms holds significant promise for developing novel strategies to combat stubborn plant pathogens. [Graphic: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

A well-developed rhizospheric system is crucial for maize to adapt to environmental stresses, thereby enhancing yield and quality. However, nitrogen (N) stress significantly impedes rhizospheric development and growth in maize. The genetic responses of maize’s rhizosphere to N stress under monocropping systems with exogenous inorganic N fertilization and intercropping systems reliant on biological N fixation are not well understood, especially regarding common and specific response genes. Therefore, through transcriptomic analysis, this study systematically investigated the gene expression and molecular responses of maize’s rhizosphere under two N supply regimes to N stress. The results showed that N stress generated 196 common and 3350 specific differentially expressed genes across the two systems, with the intercropping system exhibiting a stronger specific response. KEGG analysis revealed that the common genes, though few, are involved in key pathways essential for crop growth. Maize monocropping specific differentially expressed genes (MM) were enriched in pathways related to membrane lipids, cell wall formation, and intracellular signaling, while maize/alfalfa intercropping specific differentially expressed genes (MA) were linked to stress resistance through the glutathione metabolic pathway. WGCNA analysis identified five co-expression modules (CM). MA significantly increased the transcription factor families and structural domains directly targeting rhizospheric growth and development genes, including AP2, GRAS, Cys2His2 Zinc Finger, and LBD in CM blue. Conversely, MM significantly increased the transcription factor families and NAC structural domain targeting the promoters of N transporter protein genes in CM pink. This study emphasizes the importance of both common and specific genes in maintaining maize growth under suboptimal N supply in monocropping and intercropping systems.

The inexorable progression of neurodegenerative diseases (NDs), including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and multiple sclerosis, is closely related to irreversible brain decline. Accurately characterizing pathophysiological features and identifying reliable biomarkers for early diagnosis and optimized treatment are critical. Hindered by the blood–brain barrier (BBB), obtaining sensitive monitoring indicators for disease progression and achieving efficient drug delivery remain significant challenges. Exosomes, endogenous nanoscale vesicles that carry key bioactive substances, reflect the intracellular environment and play an important role in cell signaling. They have shown promise in traversing the BBB, serving dual roles as potential biomarkers for NDs and vehicles for targeted drug delivery. However, the specific mechanisms by which exosome influence NDs are not fully understood, necessitating further investigation into their attributes and functionalities in the context of NDs. This review explores how exosomes mediate multifaceted interactions, particularly in exacerbating pathogenic processes such as oxidative stress, neuronal dysfunction, and apoptosis integral to NDs. It provides a comprehensive analysis of the profound impact of exosomes under stress and disease states, assessing their prospective utility as biomarkers and drug delivery vectors, offering new perspectives for tackling these challenging diseases.

Sulfur (S) is an essential nutrient for plant growth, influencing not only crop yields but also the composition and function of soil microbial communities. However, the differential effects of S fertilization on abundant and rare taxa in agricultural soils remain poorly understood. This study investigates the impact of different S fertilizer types on maize yield and the structure and stability of soil microbial communities, with a particular focus on abundant and rare taxa. S fertilization led to significant increases maize yield on two typical soils (black soil and sandy soil) (5.3–24.3%) and altered soil properties, including reducing pH (0.04–0.20) and increasing the available sulfur (AS) content (3.8–8.0 mg kg−1), with ammonium sulfate having a more pronounced effect than elemental sulfur. Microbial analysis revealed distinct impacts on the diversity and community structure of both abundant and rare taxa. Elemental sulfur reduced the alpha diversity of abundant taxa more than ammonium sulfate, while NMDS indicated significant shifts in community structures, particularly among abundant taxa. Network analysis showed that S fertilization decreased the complexity of microbial interactions among rare taxa, with ammonium sulfate leading to simpler networks and elemental sulfur resulting in higher modularity. SEM highlighted that the diversity of rare taxa played a crucial role in influencing maize yield, alongside direct effects from soil properties such as AS and SAR (aryl sulfatase). Functional predictions demonstrated that amino acid metabolism and xenobiotic biodegradation and metabolism pathways were enriched in rare taxa, suggesting significant implications for soil health and crop productivity. This study provides new insights into the roles of abundant and rare bacterial taxa under S fertilization, emphasizing their importance in optimizing fertilization strategies for enhanced crop yield in specific soil types.

BackgroundEvaluating the correlation between serum potassium and Parkinson’s disease (PD) in US adults.MethodsA cross-sectional study was conducted on 20,495 adults aged 40 years or older using NHANES data from 2005 to 2020. The study utilized one-way logistic regression and multifactorial logistic regression to examine the correlation between serum potassium levels and PD. Additionally, a smoothed curve fitting approach was employed to assess the concentration-response relationship between serum potassium and PD. Stratified analyses were carried out to investigate potential interactions between serum potassium levels and PD with variables such as age, sex, race, marital status, education, BMI, smoking and medical conditions like coronary, stroke, diabetes, hypertension, and hypercholesterolemia.ResultsIn this study, a total of 20,495 participants, comprising 403 PD and 20,092 non-PD individuals, were included. After adjusted for covariates, multivariable logistic regression revealed that high serum potassium level was an independent risk factor for PD (OR:1.86, 95% CI:1.45 ~ 2.39, p 0.05).ConclusionSerum potassium levels are elevated in patients with Parkinson's disease compared to non-PD patients. Additional prospective studies are required to explore the significance of serum potassium levels in individuals with Parkinson's disease.

Summary: Background: Hospitals in China are classified into tiers (1, 2 or 3), with the largest (tier 3) having more equipment and specialist staff. Differential health insurance cost-sharing by hospital tier (lower deductibles and higher reimbursement rates in lower tiers) was introduced to reduce overcrowding in higher tier hospitals, promote use of lower tier hospitals, and limit escalating healthcare costs. However, little is known about the effects of differential cost-sharing in health insurance schemes on choice of hospital tiers. Methods: In a 9-year follow-up of a prospective study of 0.5 M adults from 10 areas in China, we examined the associations between differential health insurance cost-sharing and choice of hospital tiers for patients with a first hospitalisation for stroke or ischaemic heart disease (IHD) in 2009–2017. Analyses were performed separately in urban areas (stroke: n = 20,302; IHD: n = 19,283) and rural areas (stroke: n = 21,130; IHD: n = 17,890), using conditional logit models and adjusting for individual socioeconomic and health characteristics. Findings: About 64–68% of stroke and IHD cases in urban areas and 27–29% in rural areas chose tier 3 hospitals. In urban areas, higher reimbursement rates in each tier and lower tier 3 deductibles were associated with a greater likelihood of choosing their respective hospital tiers. In rural areas, the effects of cost-sharing were modest, suggesting a greater contribution of other factors. Higher socioeconomic status and greater disease severity were associated with a greater likelihood of seeking care in higher tier hospitals in urban and rural areas. Interpretation: Patient choice of hospital tiers for treatment of stroke and IHD in China was influenced by differential cost-sharing in urban areas, but not in rural areas. Further strategies are required to incentivise appropriate health seeking behaviour and promote more efficient hospital use. Funding: Wellcome Trust, Medical Research Council, British Heart Foundation, Cancer Research UK, Kadoorie Charitable Foundation, China Ministry of Science and Technology, and National Natural Science Foundation of China.

This opinion piece highlights the integral role of generative Artificial Intelligence (AI) in learning within Higher Education Institutions (HEIs). Employing social learning theories, this opinion piece aims to explore generative AI as a stakeholder in learning. By weaving in social constructivist and learning theories, this opinion paper aims to uncover the capacity of generative AI to facilitate and enhance the learning process. Central to this opinion piece proposition is cultivating a learning community that leverages AI's potential as a new learning stakeholder. This opinion piece aims to contribute to ongoing discussions in the field of learning development by offering a fresh outlook on how AI can be an asset in knowledge co-creation and collaborative learning. The paper does this in the following ways: (1) highlights how generative AI can effectively contribute to learning and knowledge co-creation, and (2) provides some guidance for integrating generative AI in collaborative learning.

IntroductionThis study assessed the effects of S application on maize yields and soil bacterial communities across four sites with different soil types and three S application rates (0 kg ha-1, 30 kg ha-1, and 90 kg ha-1).MethodsChanges in soil properties, bacterial community diversity, structure, and their contributions to maize production were evaluated post-S application treatments.Results(1) S application decreased soil pH, increased available sulfur (AS), and boosted maize yields in all soil types. (2) Reduced Chao1 and Shannon diversity indices were observed in black soil after S application. (3) Bacterial community structure was significantly affected by S application, except in sandy soil, impacting key stone taxa abundance. (4) Black soil showed higher sensitivity to S application due to less stable bacterial community structure. (5) Soil physicochemical indicators altered by S application, such as AS and pH, mediated bacterial diversity, influencing maize yield. Organic matter (OM) had the most significant direct positive effect on yield, followed by AS and bacterial community diversity.DiscussionThis study emphasizes the impact of S application on soil properties and bacterial communities in diverse soil types. Understanding these mechanisms can guide precision S application practices for maize yield regulation.

Abstract A perturbation treatment is derived for weakly deformed microdisk cavities in a more generalized scenario, where both resonant and non‐resonant surface scattering processes coexist. It is proved that the originally developed nondegenerate and degenerate perturbation theories are simplified forms of the generalized theory in special cases. The validity of the perturbation theory is verified by the comparison with a full numerical method for two generic classes of deformed microdisk cavities: locally notched microdisks and smooth globally deformed microdisks. The simulation of these two classes of microdisk cavities using the perturbation theory unveils the distinct characteristics of optical modes from the ones predicted by the original nondegenerate and degenerate perturbation theories in the generalized scenario. Furthermore, a hybrid‐scattering‐based exceptional point is introduced for deformed microdisk cavities in the generalized scenario by using the perturbation theory. The exceptional point exhibits higher nonorthogonality over the originally proposed resonant‐scattering‐based exceptional point, as non‐resonant scattering processes provide an additional degree of freedom. Full numerical simulations demonstrate that the exceptional point is more robust against random surface roughness at cavity boundary than the resonant‐scattering‐based exceptional point.

Summary: Background: Lynch Syndrome (LS) is a cancer predisposition syndrome caused by constitutional pathogenic variants in the mismatch repair (MMR) genes. To date, fragmentation of clinical and genomic data has restricted understanding of national LS ascertainment and outcomes, and precluded evaluation of NICE guidance on testing and management. To address this, via collaboration between researchers, the National Disease Registration Service (NDRS), NHS Genomic Medicine Service Alliances (GMSAs), and NHS Regional Clinical Genetics Services, a comprehensive registry of LS carriers in England has been established. Methods: For comprehensive ascertainment of retrospectively identified MMR pathogenic variant (PV) carriers (diagnosed prior to January 1, 2023), information was retrieved from all clinical genetics services across England, then restructured, amalgamated, and validated via a team of trained experts in NDRS. An online submission portal was established for prospective ascertainment from January 1, 2023. The resulting data, stored in a secure database in NDRS, were used to investigate the demographic and genetic characteristics of the cohort, censored at July 25, 2023. Cancer outcomes were investigated via linkage to the National Cancer Registration Dataset (NCRD). Findings: A total of 11,722 retrospective and 570 prospective data submissions were received, resulting in a comprehensive English National Lynch Syndrome Registry (ENLSR) comprising 9030 unique individuals. The most frequently identified pathogenic MMR genes were MSH2 and MLH1 at 37.2% (n = 3362) and 29.1% (n = 2624), respectively. 35.9% (n = 3239) of the ENLSR cohort received their LS diagnosis before their first cancer diagnosis (presumptive predictive germline test). Of these, 6.3% (n = 204) developed colorectal cancer, at a median age of initial diagnosis of 51 (IQR 40–62), compared to 73 years (IQR 64–80) in the general population (p

ABSTRACT: Objectives: The aim of this study was to characterise the whole genome sequence of multidrug-resistant Streptococcus pluranimalium strain SP21–2 of swine origin in China. Methods: Illumina Miseq (200X coverage) and Nanopore PromethION platform (100X coverage) were used for genome sequencing. Rapid Annotation using Subsystem Technology (RAST) was used to annotate the genome of SP21–2. The antimicrobial resistance genes (ARGs) were identified using ResFinder-4.1. Results: The assembled circular genome of S. pluranimalium SP21–2 was 1,987,058 bp in length with a GC content of 39.54%, and no plasmid sequence was detected. A total of 2086 coding sequences were predicted by RAST. Oxazolidinone-phenicol resistance gene, optrA, and pleuromutilin-lincosamide-streptogramin A resistance gene, lsa(E), are both located on chromosomes, associated with IS1216 and ISS1S, respectively. In addition, SP21–2 harbours lnu(B) (lincosamide), ant (6)-Ia and aac(6’)-aph(2”) (aminoglycoside), erm(B) (macrolide), and tet(O) (tetracycline). Conclusion: We firstly report the oxazolidinone-phenicol gene, optrA, and pleuromutilin-lincosamide-streptogramin A resistance gene, lsa(E), in S. pluranimalium. In this strain, we firstly identified ISS1S and IS1216 carrying ARGs in S. pluranimalium, which will provide a valuable reference to understanding potential transfer mechanisms of ARGs in S. pluranimalium.

The ceramic-steel-pentaerythritol ester system has a broad application prospect under high temperature conditions, which are respectively in the fields of aviation, aerospace and advanced equipment manufacturing. However, a comprehensive understanding of the friction and wear mechanisms of this system across a broad temperature range remains elusive. The tribological properties of the system at 25–475 °C were studied. With the increase of temperature, the evolution of the tribofilm follows the sequence: discontinuous tribofilm → uniform tribofilm → tribofilm removal. At 200–300 °C, an approximately 100 nm thick amorphous PxOy compound tribofilm is formed, and its nanohardness and modulus are reduced by 81.33 % and 54.02 %, respectively, compared with base steel. The tribofilm effectively reduces shear resistance by blocking friction pair contact. When the temperature exceeds 300 °C, it will lead to high-temperature coking, which adversely affects the lubrication performance. It is worth noting that the system can endure short-term service at a maximum temperature of 475 °C. Therefore, this research can help achieve continuous, stable operation of high-temperature resistant systems, as well as short-term use under extreme conditions encountered by complex equipment.

Abstract Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is identified as the cause of coronavirus disease 2019 (COVID-19) pandemic. Acute kidney injury (AKI), one of serious complications of COVID-19 infection, is the leading contributor to renal failure, associating with high mortality of the patients. This study aimed to identify the shared gene signatures and construct the gene regulatory network between COVID-19 and AKI, contributing to exploring the potential pathogenesis. Methods Utilizing the machine learning approach, the candidate gene signatures were derived from the common differentially expressed genes (DEGs) obtained from COVID-19 and AKI. Subsequently, receiver operating characteristic (ROC), consensus clustering and functional enrichment analyses were performed. Finally, protein-protein interaction (PPI) network, transcription factor (TF)-gene interaction, gene-miRNA interaction, and TF-miRNA coregulatory network were systematically undertaken. Results We successfully identified the shared 6 candidate gene signatures (RRM2, EGF, TMEM252, RARRES1, COL6A3, CUBN) between COVID-19 and AKI. ROC analysis showed that the model constructed by 6 gene signatures had a high predictive efficacy in COVID-19 (AUC = 0.965) and AKI (AUC = 0.962) cohorts, which had the potential to be the shared diagnostic biomarkers for COVID-19 and AKI. Additionally, the comprehensive gene regulatory networks, including PPI, TF-gene interaction, gene-miRNA interaction, and TF-miRNA coregulatory networks were displayed utilizing NetworkAnalyst platform. Conclusions This study successfully identified the shared gene signatures and constructed the comprehensive gene regulatory network between COVID-19 and AKI, which contributed to predicting patients’ prognosis and providing new ideas for developing therapeutic targets for COVID-19 and AKI.

Abstract Background A meta-analysis followed by PRISMA 2020 statement was performed aiming to present a whole prolactin and sex hormone profile in hemodialysis women. Methods Literatures were searched in PubMed, Cochrane library, Embase, and Web of science before March 11, 2023. Trial sequential analysis (TSA) was performed to test the conclusiveness of this meta-analysis. Egger’s test and trim-and-fill analysis was used to test publication bias. We took standardized mean difference (SMD) as pool effect of hormones values including prolactin (PRL), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2) and progesterone (P). This study was registered in PROSPERO and the number was CRD42023394503. Results Twenty-two articles from 13 countries were analyzed. Combining the results of TSA and meta-analysis, we found that compared with healthy control, hemodialysis women had higher PRL, follicular FSH and LH values and lower P levels (PRL: I 2 = 87%, SMD 1.24, 95% CI: 0.79–1.69, p

Photovoltaic double-skin glass is a low-carbon energy-saving curtain wall system that uses ventilation heat exchange and airflow regulation to reduce heat gain and generate a portion of electricity. By developing a theoretical model of the ventilated photovoltaic curtain wall system and conducting numerical simulations, this study analyzes the variation patterns of the power generation efficiency of photovoltaic glass for different inclination angles, seasons, thermal ventilation spacing, and glass transmittance in the photovoltaic double-skin curtain wall system. The results indicate a positive correlation between the surface temperature of photovoltaic glass and both ground temperature and solar radiation intensity. Additionally, photovoltaic power generation efficiency is generally higher in spring and autumn than in summer and winter, with enhanced power generation performance observed. At an inclination angle of 40°, photovoltaic panels receive optimal solar radiation and, consequently, produce the maximum electricity. Furthermore, as the ventilation spacing increases, the efficiency of power generation initially rises, reaching a peak at approximately 0.4 m, where it is 0.4% greater than at a spacing of 0.012 m. For a photovoltaic glass transmittance of 40%, the highest photovoltaic power generation efficiency is 63%, while the average efficiency is 35.3%. This has significant implications for the application and promotion of photovoltaic double-skin glass curtain walls.

With the development of technical requirements, the current challenges faced by bearing materials mainly revolve around high-temperature conditions and the trend towards material lightweighting. Full ceramic bearings are the new candidate due to their excellent properties. This article details the tribological and adsorption performance of chlorophenyl silicone oil (CPSO) as a high-temperature lubricant in ceramic tribological systems (ZrO2, Al2O3, and Si3N4). Among the three ceramic tribological systems, the lubrication performance can be ordered as Si3N4 > Al2O3 > ZrO2, as the wear rates of the ZrO2 and Al2O3 tribo-systems are almost 1135.67 and 283.33 times larger than that of the Si3N4 tribo-system, respectively. The observed results can be explained by the superior adsorption performance of CPSO on a Si3N4 ceramic surface, which was calculated by molecular dynamic simulation. The molecular dynamic simulation results show the adsorption energy of CPSO/Si3N4 is almost 54.09 and 61.18 times higher compared to that on ZrO2 and Al2O3 ceramics. These findings provide experimental and theoretical insights for understanding the lubrication performance of CPSO in a full ceramic tribo-system.

Foreign fibers directly impact the quality of raw cotton, affecting the prices of textile products and the economic efficiency of cotton textile enterprises. The accurate differentiation and labeling of foreign fibers require domain-specific knowledge, and labeling scattered cotton foreign fibers in images consumes substantial time and labor costs. In this study, we propose a semi-supervised foreign fiber detection approach that uses unlabeled image information and a small amount of labeled data for model training. Our proposed method, Efficient YOLOv5-cotton, introduces CBAM to address the issue of the missed detection and false detection of small-sized cotton foreign fibers against complex backgrounds. Second, the algorithm designs a multiscale feature information extraction network, SPPFCSPC, which improves its ability to generalize to fibers of different shapes. Lastly, to reduce the increased network parameters and computational complexity introduced by the SPPFCSPC module, we replace the C3 layer with the C3Ghost module. We evaluate Efficient YOLOv5 for detecting various types of foreign fibers. The results demonstrate that the improved Efficient YOLOv5-cotton achieves a 1.6% increase in mAP@0.5 (mean average precision) compared with the original Efficient YOLOv5 and reduces model parameters by 10% compared to the original Efficient YOLOv5 with SPPFCSPC. Our experiments show that our proposed method enhances the accuracy of foreign fiber detection using Efficient YOLOv5-cotton and considers the trade-off between the model size and computational cost.

Abstract Two types of exploratory touch including active sliding and passive sliding are usually encountered in the daily life. The friction behavior of the human finger against the surface of objects is important in tactile perception. The neural mechanisms correlating to tribological behavior are not fully understood. This study investigated the tactile response of active and passive finger friction characterized with functional near-infrared spectroscopy (fNIRS). The friction test and fNIRS test were performed simultaneously using the tactile stimulus of polytetrafluoroethylene (PTFE) specimens. Results showed that the sliding modes did not obviously influence the friction property of skin. While three cortex regions were activated in the prefrontal cortex (PFC), showing a higher activation level of passive sliding. This revealed that the tribological performance was not a simple parameter to affect tactile perception, and the difference in cortical hemodynamic activity of active and passive touch was also recognised. The movement-related blood flow changes revealed the role of PFC in integrating tactile sensation although there was no estimation task on roughness perception.

Abstract Duct-dependent congenital heart diseases (CHDs) are a serious form of CHD with a low detection rate, especially in underdeveloped countries and areas. Although existing studies have developed models for fetal heart structure identification, there is a lack of comprehensive evaluation of the long axis of the aorta. In this study, a total of 6698 images and 48 videos are collected to develop and test a two-stage deep transfer learning model named DDCHD-DenseNet for screening critical duct-dependent CHDs. The model achieves a sensitivity of 0.973, 0.843, 0.769, and 0.759, and a specificity of 0.985, 0.967, 0.956, and 0.759, respectively, on the four multicenter test sets. It is expected to be employed as a potential automatic screening tool for hierarchical care and computer-aided diagnosis. Our two-stage strategy effectively improves the robustness of the model and can be extended to screen for other fetal heart development defects.

Abstract Background PAX1 gene methylation plays an important role in the development of cervical cancer. However, its prognostic value after radiotherapy for locally advanced cervical cancer is unknown, so this study aimed to investigate the value of PAX1 gene methylation for predicting the sensitivity of radiotherapy for cervical cancer. Methods We selected 125 patients with primary cervical cancer who underwent concurrent chemo-radiotherapy as the study population, quantitative methylation-specific polymerase chain reaction (QMSP) was used for detecting PAX1 methylation status of cervical exfoliated cells. Logistic regression model was used to analyze the risk factors associated with the short-term efficacy and to establish a prediction model of radiotherapy sensitivity based on PAX1 gene methylation. Cell viability after radiation of Hela and SiHa cells transfected with PAX1 or control vector was evaluated by CCK8. Furthermore, RNA-Seq analyses identified different expressed genes (DEGs) in PAX1 overexpressed SiHa cells. Gene Ontology (GO) and pathway enrichment analysis was carried out to determine the biological function of DEGs. Results PAX1 methylation level was associated with HPV16/18-positive rate. PAX1 hypomethylation was found to be a risk factor for tumor residual after chemo-radiotherapy. A nomogram containing the risk factors for PAX1 methylation status, lymph node metastasis, pathological type and tumor size was further constructed to predict the probability of tumor residual after chemo-radiotherapy (AUC = 0.823, 95% CI 0.736–0.910). High PAX1 protein level was more likely to cause radioresistance in both Hela and SiHa cells. Transcriptomic sequencing of PAX1 overexpressed and control cells identified 615 differentially expressed genes, and GO enrichment analysis suggested that PAX1 may be involved in the regulation of signaling receptor activity and response to viruses. Conclusion PAX1 hypomethylation status could be used as a promising biomarker to predict radioresistance in cervical cancer. This further provides a new idea for the individualized treatment strategy of simultaneous radiotherapy for cervical cancer.

Abstract The quantized bulk quadrupole moment has so far revealed a non-trivial boundary state with lower-dimensional topological edge states and in-gap zero-dimensional corner modes. In contrast to photonic implementations, state-of-the-art strategies for topological thermal metamaterials struggle to achieve such higher-order hierarchical features. This is due to the absence of quantized bulk quadrupole moments in thermal diffusion fundamentally prohibiting possible band topology expansions. Here, we report a recipe for generating quantized bulk quadrupole moments in fluid heat transport and observe the quadrupole topological phases in non-Hermitian thermal systems. Our experiments show that both the real- and imaginary-valued bands exhibit the hierarchical features of bulk, gapped edge and in-gap corner states—in stark contrast to the higher-order states observed only on real-valued bands in classical wave fields. Our findings open up unique possibilities for diffusive metamaterial engineering and establish a playground for multipolar topological physics.

Abstract Immune engineering, a burgeoning field within regenerative medicine, involves a spectrum of strategies to optimize the intricate interplay between tissue regenerative biomaterials and the host tissue. These strategies are applied across different types of biomaterials and various disease models, which encompasses finely modulating the immune response at the levels of immune cells and factors, aiming to mitigate adverse effects like fibrosis and persistent inflammation that may arise at the injury site and consequently promote tissue regeneration. With the continuous progress in electrospinning technology, the immunoregulatory capabilities of electrospun fibers have gained substantial attention over the years. Electrospun fibers, with their extracellular matrix‐like characteristics, high surface‐area‐to‐volume ratio, and reliable pharmaceutical compound capacity, have emerged as key players among tissue engineering materials. This review specifically focuses on the role of electrospun fiber‐based immune engineering, emphasizing their unique design strategies. Notably, electrospinning actively engages in immune engineering by modulating immune responses through four essential strategies: (i) surface modification, (ii) drug loading, (iii) physicochemical parameters, and (iv) biological grafting. This review presents a comprehensive overview of the intricate mechanisms of the immune system in injured tissues while unveiling the key strategies adopted by electrospun fibers to orchestrate immune regulation. Furthermore, the review explores the current developmental trends and limitations concerning the immunoregulatory function of electrospun fibers, aiming to drive the advancements in electrospun fiber‐based immune engineering to its full potential.

Background: Preconditioning is a promising strategy against ischemic brain injury, and numerous studies in vitro and in vivo have demonstrated its neuroprotective effects. However, at present there is no bibliometric analysis of preconditioning in cerebral ischemia. Therefore, a comprehensive overview of the current status, hot spots, and emerging trends in this research field is necessary. Materials and methods: Studies on preconditioning in cerebral ischemia from January 1999–December 2022 were retrieved from the Web of Science Core Collection (WOSCC) database. CiteSpace was used for data mining and visual analysis. Results: A total of 1738 papers on preconditioning in cerebral ischemia were included in the study. The annual publications showed an upwards and then downwards trend but currently remain high in terms of annual publications. The US was the leading country, followed by China, the most active country in recent years. Capital Medical University published the largest number of articles. Perez-Pinzon, Miguel A contributed the most publications, while KITAGAWA K was the most cited author. The focus of the study covered three areas: (1) relevant diseases and experimental models, (2) types of preconditioning and stimuli, and (3) mechanisms of ischemic tolerance. Remote ischemic preconditioning, preconditioning of mesenchymal stem cells (MSCs), and inflammation are the frontiers of research in this field. Conclusion: Our study provides a visual and scientific overview of research on preconditioning in cerebral ischemia, providing valuable information and new directions for researchers.

A high-energy picosecond 355 nm ultraviolet (UV) laser operating at 100 Hz was demonstrated. A 352 mJ, 69 ps, 1064 nm laser at 100 Hz was realized firstly by cascaded regenerative, laser diode end-pumped single-pass and side-pumped main amplifiers. The stimulated Raman scattering-based beam shaping technique, thermally induced birefringence compensation and 4f spatial filter-image relaying systems were used to maintain a relatively homogeneous beam intensity distribution during the amplification process. By using lithium triborate crystals for second- and third-harmonic generation (THG), a 172 mJ, approximately 56 ps, 355 nm UV laser was achieved with a THG conversion efficiency of 49%. To the best of our knowledge, it is the highest pulse energy of a picosecond 355 nm UV laser so far. The beam quality factor ${M}^2$ and pulse energy stability were ${M}_x^2$ =3.92, ${M}_y^2$ =3.71 and root mean square of 1.48%@3 hours. This laser system could play significant roles in applications including photoconductive switch excitation, laser drilling and laser micro-fabrication.

This study examines how various environmental and economic variables contribute to environmental degradation. Industrialization, trade openness, and foreign direct investment are among the variables, as are environmental diplomacy, environmental diplomacy secure, and renewable energy consumption. Therefore, the data covers the years 1991-2020, and our sample includes all 19 countries and two groups (the European Union and the African Union). The research used the Pesaran CD test to determine cross-section dependency, CIPS and CADF test to determine stationarity, the Wald test for hetrodcedasasticity and the Wooldridge test for autocorrelation; therefore, VIF for multicollinearity, Durbin and Hausman to analyze the endogeneity. It also employed Westerlund's cointegration test to ensure cross-sectional dependence, Wald test for group-wise heteroscedasticity, Wooldridge test for autocorrelation, VIF for multicollinearity, and Durbin and Hausman for endogeneity. The two-step system generalized method of moments (GMM) is used to estimate the results and confirm the relationship between independent variables (Industrialization, trade openness, FDI, environmental diplomacy, secure environmental diplomacy, and renewable energy) and dependent variables (Environmental Degradation) in G20 countries. Therefore, Industrialization, trade openness, foreign direct investment, ecological diplomacy, and renewable energy consumption significantly impact ecological degradation. Environmental diplomacy is crucial to combat degradation and stimulate global collaboration. G20 nations enact strict environmental restrictions to tackle climate change and encourage economic growth.

Non-motor symptoms are prevalent among individuals with Parkinson’s disease (PD) and seriously affect patient quality of life, even more so than motor symptoms. In the past decade, an increasing number of studies have investigated non-motor symptoms in PD. The present study aimed to comprehensively analyze the global literature, trends, and hotspots of research investigating non-motor symptoms in PD through bibliometric methods. Studies addressing non-motor symptoms in the Web of Science Core Collection (WoSCC), published between January 2013 and December 2022, were retrieved. Bibliometric methods, including the R package “Bibliometrix,” VOS viewer, and CiteSpace software, were used to investigate and visualize parameters, including yearly publications, country/region, institution, and authors, to collate and quantify information. Analysis of keywords and co-cited references explored trends and hotspots. There was a significant increase in the number of publications addressing the non-motor symptoms of PD, with a total of 3,521 articles retrieved. The United States was ranked first in terms of publications (n = 763) and citations (n = 11,269), maintaining its leadership position among all countries. King’s College London (United Kingdom) was the most active institution among all publications (n = 133) and K Ray Chaudhuri was the author with the most publications (n = 131). Parkinsonism & Related Disorders published the most articles, while Movement Disorders was the most cited journal. Reference explosions have shown that early diagnosis, biomarkers, novel magnetic resonance imaging techniques, and deep brain stimulation have become research “hotspots” in recent years. Keyword clustering revealed that alpha-synuclein is the largest cluster for PD. The keyword heatmap revealed that non-motor symptoms appeared most frequently (n = 1,104), followed by quality of life (n = 502), dementia (n = 403), and depression (n = 397). Results of the present study provide an objective, comprehensive, and systematic analysis of these publications, and identifies trends and “hot” developments in this field of research. This work will inform investigators worldwide to help them conduct further research and develop new therapies.

Background: Malignancies with BRCA1/2 deficiencies are particularly sensitive to PARP inhibitors. Thus, combining PARP inhibitors with agents that impair DNA damage repair to treat BRCA1/2 wild-type PDAC could broaden the clinical use of these promising PARP inhibitors. Here we examined the synergism and mechanism of oncolytic measles virus (rMV-Hu191) with a PARP inhibitor (Olaparib) in vitro and in vivo. Methods: The cell viability assay, cell cycle analysis, colony formation assay, TCID 50 method, western blotting, flow cytometry, DNA comet assay, Mice bearing PDAC xenografts, IF, IHC and TUNEL assay were performed to explore the antitumor efficacy and underlying mechanisms. Results: In this study, we explored the antitumor activities of rMV-Hu191 and Olaparib in two PDAC cell lines harboring wild-type BRCA1/2 genes. Compared to monotherapy, the combination of rMV-Hu191 and Olaparib was able to synergistically cause growth arrest, apoptotic cell death and DNA damage, accompanying with excessive oxidative stress. Mechanistically, the data indicated that the observed synergy depended on the oxidative DNA damage and ROS-dependent apoptosis generating by rMV-Hu191 combined with Olaparib in human PDAC cells. Tumor inhibition and prolonged survival of PDAC mice xenografts in vivo confirmed the synergism of combinational treatment with trivial side-effects. Conclusions: Our findings firstly suggested that combination treatment with rMV-Hu191 and Olaparib had a profound and synergistic therapeutic effect against human PDAC through synthetic lethality. In conclusion, we recommend combining oncolytic rMV-Hu191 with a PARP inhibitor (Olaparib) as a novel therapeutic strategy and provided a potential mechanism for advanced PDAC regardless of BRCA mutation status.

Wettability is one of the important physical properties of reservoir rock surfaces, and it is a key factor affecting capillary force, relative permeability, bound water saturation and fluid micro-distribution. Based on the molecular simulation method, this paper made a study of the wetting behavior of a graphite surface (organic surface) modified by the oxygen-containing functional groups and the distribution characteristics of the methane-water system in organic slit pores. The results showed that the interaction energy between the water molecules and the surface decreased and the wetting contact angle of the organic matter surface increased with the increase in the oxygen-containing functional groups; with the increase in the temperature, the interaction energy between the organic matter surface and the water molecules increased, and the wetting contact angle decreased; in the graphite slit pore model with symmetrical C/O ratio, water molecules were symmetrically distributed near the wall of oxygen-containing functionalized graphite, and with the decreasing in the C/O ratio, the relative concentration of water molecules increased and the diffusion coefficient decreased, while methane molecules were clustered in the center of the pore. In the graphite slit pore model with asymmetric C/O ratio, the water molecules were asymmetrically distributed near the wall of the oxygenated functionalized graphite, while the methane molecules were clustered in the center of the pore, where the side with a low C/O ratio had strong hydrophilicity on the wall and a high relative concentration of water molecules, while the side with a high C/O ratio had strong hydrophobicity on the wall and a low relative concentration of water molecules. The research findings were extremely significant to make a study of the influences of shale reservoir characteristics.

Abstract Complicated tribological behavior occurs when human fingers touch and perceive the surfaces of objects. In this process, people use their exploration style with different conditions, such as contact load, sliding speed, sliding direction, and angle of orientation between fingers and object surface consciously or unconsciously. This work addressed interlaboratory experimental devices for finger active and passive tactile friction analysis, showing two types of finger movement. In active sliding experiment, the participant slid their finger freely against the object surface, requiring the subject to control the motion conditions themselves. For passive sliding experiments, these motion conditions were adjusted by the device. Several analysis parameters, such as contact force, vibration acceleration signals, vibration magnitude, and fingerprint deformation were recorded simultaneously. Noticeable friction differences were observed when comparing active sliding and passive sliding. For passive sliding, stick-slip behavior occurred when sliding in the distal direction, evidenced by observing the friction force and the related deformation of the fingerprint ridges. The employed devices showed good repeatability and high reliability, which enriched the design of the experimental platform and provided guidance to the standardization research in the field of tactile friction.

Anti-aging functional foods benefit the elderly. Telomeres are chromosomal ends that maintain genome stability extended by telomerase catalytic subunit TERT. Due to the end-replication problem, telomeres shorten after each cell cycle without telomerase in most human cells, and eventually the cell enters the senescence stage. Natural products can attenuate the aging process by increasing telomerase activity, such as TA-65. However, TA-65 is expensive. Other Chinese natural products may achieve comparable effects. Here, we found that Rosa roxburghii fruit extracts effectively increase TERT expression and telomerase activity in cultured human mesenchymal stem cells. Both R. roxburghii fruit extracts obtained by freeze-drying and spray-drying increased the activity of telomerase. R. roxburghii fruit extracts were able to reduce reactive oxygen species levels, enhance superoxide dismutase activity, and reduce DNA damage caused by oxidative stress or radiation. R. roxburghii fruit extracts promoted cell proliferation, improved senescent cell morphology, delayed replicative cellular senescence, attenuated cell cycle suppressors, and alleviated the senescence-associated secretory phenotype. Transcriptome and metabolic profiling revealed that R. roxburghii fruit extracts promote DNA replication and telomere maintenance pathways and decrease triglyceride levels. Overall, we provide a theoretical basis for the application of R. roxburghii fruit as an anti-aging product.

Aspergillus fumigatus is a common causative pathogen of aspergillosis. At present, triazole resistance of A. fumigatus poses an important challenge to human health globally. In this study, the biological characteristics and mechanisms of azole resistance of five A. fumigatus strains (AF1, AF2, AF4, AF5, and AF8) were explored. There were notable differences in the sporulation and biofilm formation abilities of the five test strains as compared to the standard strain AF293. The ability of strain AF1 to avoid phagocytosis by MH-S cells was significantly decreased as compared to strain AF293, while that of strains AF2, AF4, and AF5 were significantly increased. Fungal burden analysis with Galleria mellonella larvae revealed differences in pathogenicity among the five strains. Moreover, the broth microdilution and E-test assays confirmed that strains AF1 and AF2 were resistant to itraconazole and isaconazole, while strains AF4, AF5, and AF8 were resistant to voriconazole and isaconazole. Strains AF1 and AF2 carried the cyp51A mutations TR34/L98H/V242I/S297T/F495I combined with the hmg1 mutation S541G, whereas strains AF4 and AF8 carried the cyp51A mutation TR46/Y121F/V242I/T289A, while strain AF5 had no cyp51A mutation. Real-time quantitative polymerase chain reaction (RT-qPCR) analysis revealed differences in the expression levels of genes associated with ergosterol synthesis and efflux pumps among the five strains. In addition, transcriptomics, RT-qPCR, and the NAD+/NADH ratio demonstrated that the mechanism of voriconazole resistance of strain AF5 was related to overexpression of genes associated with energy production and efflux pumps. These findings will help to further elucidate the triazole resistance mechanism in A. fumigatus.