Search

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%.

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.

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.

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.

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.

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.

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.

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.

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.

Plants communicate underground by secreting multiple amino acids (AAs) through their roots, triggering defense mechanisms against cadmium (Cd) stress. However, the specific roles of the individual AAs in Cd translocation and detoxification remain unclear. This study investigated how exogenous AAs influence Cd movement from the roots to the shoots in Cd-resistant and Cd-sensitive Chinese cabbage cultivars (Jingcui 60 and 16-7 cultivars). The results showed that methionine (Met) and cysteine (Cys) reduced Cd concentrations in the shoots of Jingcui 60 by approximately 44% and 52%, and in 16-7 by approximately 43% and 32%, respectively, compared to plants treated with Cd alone. However, threonine (Thr) and aspartic acid (Asp) did not show similar effects. Subcellular Cd distribution analysis revealed that AA supplementation increased Cd uptake in the roots, with Jingcui 60 preferentially storing more Cd in the cell wall, whereas the 16-7 cultivar exhibited higher Cd concentrations in the organelles. Moreover, Met and Cys promoted the formation of Cd-phosphate in the roots of Jingcui 60 and Cd-oxalate in the 16-7 cultivar, respectively. Further analysis showed that exogenous Cys inhibited Cd transport to the xylem by downregulating the expression of HMA2 in the roots of both cultivars, and HMA4 in the 16-7 cultivar. These findings provide insights into the influence of exogenous AAs on Cd partitioning and detoxification in Chinese cabbage plants.

To integrate the sponge city concept into urban development, we propose an analytical approach for runoff volume control, considering urban expansion. Using Changchun City as a case study and historical land-use data, we simulated the prediction of Changchun City’s land-use structure for 2035 change with the GeoSOS-FLUS platform. We calculated storage volumes for Low Impact Development (LID) designs using 2019 and 2035 land surface data. The objective is an 80% runoff volume control rate by 2035. Through Monte Carlo simulation and sensitivity analysis, we assessed the impact of various land-use types on LID storage volume calculations. Findings show that industrial land significantly influences LID storage volumes. This highlights the need for precise surveys of industrial land properties and surface composition in sponge city planning for more accurate runoff volume control analysis in Changchun City. The results indicate that LID storage volumes based on current data may not meet long-term sponge city goals due to increased impervious surfaces and runoff coefficients during urbanization.

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.

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 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.

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.

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.

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

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.

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.

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.

In the context of sustainable agriculture and biomaterial development, understanding and enhancing plant secondary cell wall formation are crucial for improving crop fiber quality and biomass conversion efficiency. This is especially critical for economically important crops like upland cotton (Gossypium hirsutum L.), for which fiber quality and its processing properties are essential. Through comprehensive genome-wide screening and analysis of expression patterns, we identified a particularly high expression of an R2R3 MYB transcription factor, GhMYB52 Like, in the development of the secondary cell wall in cotton fiber cells. Utilizing gene-editing technology to generate a loss-of-function mutant to clarify the role of GhMYB52 Like, we revealed that GhMYB52 Like does not directly contribute to cellulose synthesis in cotton fibers but instead represses a subset of lignin biosynthesis genes, establishing it as a lignin biosynthesis inhibitor. Concurrently, a substantial decrease in the lint index, a critical measure of cotton yield, was noted in parallel with an elevation in lignin levels. This study not only deepens our understanding of the molecular mechanisms underlying cotton fiber development but also offers new perspectives for the molecular improvement of other economically important crops and the enhancement of biomass energy utilization.

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.

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.

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.

The primary prerequisite for socioeconomic growth is good health, hence promoting residents' health is a vital objective of public policies. It is yet up for debate whether or not the digital economy (DE), which will be crucial to future economic growth, will eventually result in improvements in residents' health. Utilizing the China Family Panel Studies (CFPS) data in 2020, we explore how the DE affects residents' health. The findings reveal that residents' health is greatly enhanced by the DE. The eastern region sees a more dramatic improvement in residents' health as a result of the DE. Additionally, the DE can improve residents' health through the promotion of regional green development. The study's findings add to our knowledge of how the DE impacts residents' health while also offering recommendations for achieving universal health.

BackgroundEndoscopic ultrasound-guided biliary drainage (EUS-BD) is an alternative to endoscopic retrograde cholangiopancreatography (ERCP) for patients with obstructive jaundice. However, it is still a challenge for many endoscopists because of its novelty and complexity. This study aimed to establish an ideal bile duct dilatation model for the training and practice of endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS).MethodsThe 34 healthy Bama miniature pigs were divided into the part of developing the standardized EUS-CDS (n=9) and the part of trainees training (n=25). Part one, two different methods were used to clip Vater’s ampulla using metal clips to establish an extrahepatic bile duct dilatation model. Part two, five trainees were trained on EUS-CDS with 25 pigs. Following a 2-week observation period, the feasibility and effectiveness of the technique were evaluated.ResultsIn the group with three metal clips perpendicular to the duodenal wall clipping Vater’s ampulla, the success rate of extrahepatic bile duct dilation greater than 1 cm in 24 h was 5/6, whereas the remaining one pig was 48 h. All five trainees can finally complete the EUS-CDS independently. No death occurred during the 2-week observation period.ConclusionClipping Vater’s ampulla with three metal clips perpendicular to the duodenal wall is an effective and stable method to create a porcine bile duct dilatation model.

The primary purpose of this research is to examine the impact of climate change on maize production in Pakistan. This research studied the impact of climate change on maize production in Pakistan from 1990 to 2020 using the Auto Regressive Distributed Lag (ARDL) technique and draws implications for the future of Pakistan's sustainable agricultural industry. According to ARDL's short-run and long-run analyses, variables such as average temperature (AVEGTP), carbon dioxide (CO2), precipitation (PRPT), and tube well irrigation (TWL) all have a significant short-run and long-run impact on maize yield at the 1 %, 5 %, and 10 % significance levels. The estimated findings were also affirmed through FMOLS and DOLS. The study's key findings indicated that variables such as average temperature, carbon dioxide, precipitation, and tube well irrigation had significant short-run and long-run impacts on maize yield. Climate change's impacts on maize yield underline the crucial need for action to address this global issue and ensure agriculture's future. A recent study has emphasized the significant impact of climate change on Pakistan's maize production, stressing the importance of addressing this global issue for food security. The study recommends selecting crop varieties and managing fertilizer applications based on projected climate change to mitigate the impending crisis. Policymakers can use the study's findings as valuable insights to formulate effective policies that ensure the resilience and sustainability of Pakistan's agricultural industry.

Background: Gastric cancer (GC) develops from gastric precancerous lesions (GPL), and early diagnosis and treatment at the premalignant stage may achieve a higher benefit‒cost ratio with a reduced necessity for surgery. However, reliable noninvasive screening biomarkers of GPL are currently lacking. Methods: The marker genes of GPL encoding extracellular proteins were identified by bioinformatics analysis and further verified by immunofluorescence and immunohistochemistry assays. Serum samples were collected to measure the levels of SERPINB5, the diagnostic efficacy of which was assessed by the area under the receiver operating characteristic (ROC) curve (AUC). Finally, the effect of SERPINB5 on the phenotypic conversion of macrophages was verified by public data and in vitro experiments. Results: SERPINB5 was identified as an extracellular biomarker of GPL that had good diagnostic efficacy. High expression of SERPINB5 was observed in the epithelial cells and adjacent extracellular matrix on sections of gastric high-grade intraepithelial neoplasia (HGIN). Importantly, SERPINB5 determined in serum was significantly increased in the HGIN group, and the AUC for discriminating between HGIN and chronic gastritis or low-grade intraepithelial neoplasia was 0.9936 and 0.9750, respectively. Moreover, SERPINB5 expression was positively correlated with macrophage infiltration, and M1 marker NOS2 expression, but negatively correlated with M2 marker CSF1R expression. In THP-1-derived macrophages, SERPINB5 upregulated expression of M1-related cytokines TNF-α and IL-12, and M1 marker CD86, but suppressed production of M2-related cytokines TGF-β and IL-10. Conclusions: Our study provides evidence that SERPINB5 may serve as a promising noninvasive serum biomarker for gastric HGIN screening and regulate macrophage phenotype conversion.

ObjectiveThis investigation sought to elucidate the potential correlation between a recently characterized adiposity metric, termed the Weight-Adjusted-Waist Index (WWI) and hyperuricemia.MethodsA cross-sectional design was employed in this study, featuring both hyperuricemic and non-hyperuricemic subjects with complete WWI data, sourced from the National Health and Nutrition Examination Survey (NHANES) spanning 2017 to March 2020. WWI was calculated utilizing the formula which involves the division of waist circumference (WC) by the square root of the body weight. In order to determine the relationship between WWI and hyperuricemia, both univariate and multivariate logistic regression models, appropriately weighted, were employed in the analysis. The linearity of relationships was validated using smooth curve fitting. Additionally, subgroup evaluations and interaction assessments were conducted.ResultsThe study sample comprised 7437 subjects, yielding a hyperuricemia prevalence of 18.22%. Stratifying WWI into tertiles, a progressive rise in hyperuricemia prevalence was evident with increasing WWI (Tertile 1: 11.62%, Tertile 2: 17.91%, Tertile 3: 25.13%). The odds ratio (OR) demonstrated that individuals within the highest WWI tertile were significantly more prone to hyperuricemia than those in the lowest tertile (OR = 2.41, 95% CI: 1.88-3.08).ConclusionThis study provides evidence that an elevated WWI is correlated with an increased risk of hyperuricemia in the adult population of the United States. These results suggest that WWI may serve as a viable anthropometric indicator for predicting hyperuricemia.

BackgroundGlucose metabolism (GM) plays a crucial role in cancer cell proliferation, tumor growth, and survival. However, the identification of glucose metabolism-related genes (GMRGs) for effective prediction of prognosis in head and neck squamous cell carcinoma (HNSC) is still lacking.MethodsWe conducted differential analysis between HNSC and Normal groups to identify differentially expressed genes (DEGs). Key module genes were obtained using weighted gene co-expression network analysis (WGCNA). Intersection analysis of DEGs, GMRGs, and key module genes identified GMRG-DEGs. Univariate and multivariate Cox regression analyses were performed to screen prognostic-associated genes. Independent prognostic analysis of clinical traits and risk scores was implemented using Cox regression. Gene set enrichment analysis (GSEA) was used to explore functional pathways and genes between high- and low-risk groups. Immune infiltration analysis compared immune cells between the two groups in HNSC samples. Drug prediction was performed using the Genomics of Drug Sensitivity in Cancer (GDSC) database. Quantitative real-time fluorescence PCR (qRT-PCR) validated the expression levels of prognosis-related genes in HNSC patients.ResultsWe identified 4973 DEGs between HNSC and Normal samples. Key gene modules, represented by black and brown module genes, were identified. Intersection analysis revealed 76 GMRG-DEGs. Five prognosis-related genes (MTHFD2, CDKN2A, TPM2, MPZ, and DNMT1) were identified. A nomogram incorporating age, lymph node status (N), and risk score was constructed for survival prediction in HNSC patients. Immune infiltration analysis showed significant differences in five immune cell types (Macrophages M0, memory B cells, Monocytes, Macrophages M2, and Dendritic resting cells) between the high- and low-risk groups. GDSC database analysis identified 53 drugs with remarkable differences between the groups, including A.443654 and AG.014699. DNMT1 and MTHFD2 were up-regulated, while MPZ was down-regulated in HNSC.ConclusionOur study highlights the significant association of five prognosis-related genes (MTHFD2, CDKN2A, TPM2, MPZ, and DNMT1) with HNSC. These findings provide further evidence of the crucial role of GMRGs in HNSC.

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.

Abstract Bacteria often use multiple transcription factors to regulate specific biological processes. Biosynthesis of heat-stable antifungal factor (HSAF) is regulated by multiple factors in Lysobacter enzymogenes. However, the mechanism of HSAF biosynthesis regulation remains largely unknown. In this study, we screened a potential HSAF biosynthesis regulator, RecX, by a DNA pull-down assay. Deletion of recX resulted in a significant increase in the production of HSAF, and overexpression of recX significantly suppressed HSAF production. Importantly, our results showe that RecX directly binds to the promoter region of the lafB gene to inhibit its transcription and thus decreases HSAF production in L. enzymogenes. These findings reveal the novel mechanism of RecX regulation of antifungal antibiotic production in L. enzymogenes.

Probability of arc re-strike increases with the increment of break voltage, especially in an arc chamber of DC bridge-type contacts equipped with permanent magnets. Among all types of arc re-strikes, the most dangerous one is that part of the arc re-enters the contact gap, which is defined as swirl re-strike in this paper. In this paper, the arc images and arc voltage waveforms were analyzed, and the typical features of arc re-strike were identified. In addition, the probability of arc swirl re-strike when the supply voltages range from 270 V to 730 V and the magnetic flux densities ranges from 30 mT to 70 mT were revealed. Mechanism of the swirl re-strike is explained and it is due to the randomness of positions of both the arc igniting and the arc-root transferring on stationary contacts, as well as the non-uniformly distributed magnetic field in the arcing region. Finally, measures to prevent arc re-strike were proposed, and their effectiveness on eliminating re-strike were verified at the voltage range of up to 730V and magnetic flux. Occurrence probability of arc re-strike drops from unity to 13% at 730 V.

To investigate the susceptibility of drifting snow along the Ya’an–Qamdo section of the railway, which is located in a high-altitude and cold plateau in Southwest China with scarce meteorological information, the Weather Research and Forecasting Model (WRF) is used in this paper to simulate the spatio-temporal distribution of meteorological data. According to the varying terrain, the railway section from Ya’an to Qamdo is divided into two regions along 100.8° E for double-layer nested simulation. The original land use data of the WRF model are used in region 1. Due to the increased number of mountains in region 2, the original data are replaced by the MCD12Q1v006 land use data, and the vertical direction layers are densified near the ground to increase simulation accuracy. The simulated results are compared with the observation data. It is found that after densification, the results have been significantly improved. The results obtained by the WRF model can accurately simulate the change trends of temperature, rainfall, and wind speed, and the correlation coefficients are relatively high, which verifies the accuracy of WRF for simulating complex terrain regions. The simulation results further indicate that approximately 300 km of the Ya’an–Qamdo railway may experience drifting snow. Among them, no drifting snow events occur in Ya’an County, and the areas with higher probability are located at the border between Luding County and Tianquan County, followed by Kangding area. The remaining areas have a probability of less than 10%. The WRF model demonstrates its capability in the drifting snow protection of railways with limited meteorological data.