Search

Abstract Background Removing infectious bacteria biofilms from the root canal system is crucial for a successful endodontic treatment. This study investigated the antibacterial effect of femtosecond laser (fs-laser) against Enterococcus faecalis (E. faecalis) and Fusobacterium nucleatum (F. nucleatum) biofilms on dentin. Methods The chemical composition of dentin slices from extracted human teeth was analyzed using FTIR and Raman probes. The morphology of fs-laser ablated dentin grooves was evaluated by an optical profiler, and the fs-laser ablation fluence threshold was obtained by a mathematical model. A correlation between dentin chemical composition and ablation threshold was established. The antibacterial effect of different fs-laser irradiation dosages within the safe threshold on E. faecalis and F. nucleatum biofilms was firstly evaluated using the growth curve method. The biofilm removal efficacy on dentin and antimicrobial effect in dentinal tubules was further evaluated by CLSM and SEM analysis. The effect of fs-laser irradiation on the microhardness of dentin surface was also evaluated. The fs-laser irradiation process was observed using a spectrometer. Results The peak intensity of phosphate group showed a positive correlation to the fs-laser dentin ablation fluence threshold in both FTIR and Raman spectroscopy. The safe fluence threshold of 1.8 J/cm2 was determined by a prediction model on 20 dentin samples. The antimicrobial effect of fs-laser increased along with the irradiation fluence or time. Both E. faecalis and F. nucleatum biofilms on dentin could be effectively removed by the fs-laser with 1.5 J/cm2 fluence for 20 s without compromising the microhardness of dentin surface. Meanwhile, fs-laser could also eliminate the bacteria in dentinal tubules. The generation of plasma occurred during the fs-laser irradiation process, and the plasma spectra exhibited distinguishable characteristics between the two kinds of biofilms. Conclusions Fs-laser could effectively remove both E. faecalis and F. nucleatum biofilms on dentin, along with a notable antibacterial effect in dentinal tubules.

Objective: To investigate the protective effects of Lepidium draba L. (L. draba) on cyclophosphamide (CP)-induced hepatotoxicity and nephrotoxicity in rats. Methods: A total of 36 rats were divided into six groups as follows: the sham control group, the CP group (CP 100 mg/kg i.p. on days 1, 7, 14, 21, 28, and 35), the CP groups treated with L. draba extract (100, 200 and 400 mg/kg of L. draba extract for 28 d), and the L. draba extract alone group (400 mg/kg of L. draba extract for 28 d). Serum parameters of renal and hepatic function, as well as pro-inflammatory and anti-inflammatory cytokines associated with liver and kidney damage were measured. Moreover, Bax, Bcl-2, and caspase-3 gene expression and histopathological changes were assessed. Results: L. draba extract alleviated CP-induced hepatotoxicity and nephrotoxicity by decreasing nitric oxide, TBARS, IL-6, TNF-α, and IL-Ιβ levels, as well as increasing superoxide dismutase, catalase and glutathione peroxidase activities, and FRAP, MIF, and TGF-β levels. In addition, the extract downregulated the expression of pro-apoptotic genes (Bax and caspase-3) and mitigated the destruction of glomeruli and renal tubules as well as the degeneration of hepatocytes. Conclusions: L. draba extract can protect hepatic and renal structure and function against CP-induced toxicities, and may be used as a therapeutic agent for CP-induced hepatotoxicity and nephrotoxicity.

Abstract Ulcerative colitis (UC) is an increasingly prevalent inflammatory condition affecting the intestinal mucosa, while nonspecific orbital inflammation (NSOI) is a common non-neoplastic orbital disorder. Exploring the molecular interplay between UC and NSOI may help physicians make earlier diagnoses and enhance treatment approaches. We analyzed gene expression datasets (GSE58331, GSE105149, GSE206285, and GSE179285) for UC and NSOI from the GEO database. Using WGCNA and differential expression analysis, we identified genes commonly altered in both diseases. GO enrichment, PPI networks, and transcription factor prediction were performed using Cytoscape plugins (cytoHubba and iRegulon). Machine learning techniques were employed to assess transcription factor activity and evaluate potential therapeutic targets among the hub genes. We conducted an association analysis using the TwoSampleMR package in R to explore potential causal relationships between NSOI and UC. A total of 85 intersecting genes between NSOI and UC were identified, and enrichment analyses revealed their roles in immune and inflammatory processes. Key biomarkers, including CXCL10, CXCR4, CXCL9, CD27, SELL, MMP9, CD79A, CD3E, GZMK, and CCL19, were highlighted, linking them to processes such as leukocyte migration, viral response, and monocyte differentiation. STAT1 was identified as a shared transcription factor influencing both diseases. Machine learning algorithms identified eight potential genes for diagnostic and therapeutic use, with CXCL10 emerging as a key player in the pathogenesis of NSOI and UC. CXCL10 likely regulates CXCR4, LCK, CCR7, and other genes involved in pathways such as cytokine-cytokine receptor interactions, HIV-1 infection, and Epstein-Barr virus infection. This study offers insights into the co-pathogenic mechanisms of UC and NSOI, providing a foundation for further mechanistic research and therapeutic development.

Abstract Studies on triaxial contact stresses and asphalt pavement rutting are of great significance for traffic safety and the durability of the asphalt pavement. Our new approach considers more evaluating indicators by investigating compressive creep, vertical, and longitudinal permanent deformation to analyse asphalt pavement rutting under triaxial contact stress during typical driving conditions. For this purpose, firstly sophisticated three-dimensional finite element models encompassing the truck-bus tire and asphalt pavement temperature are developed. Secondly, a comparative analysis was conducted by collating the predicted deformations obtained through finite element analysis with the deformations measured in laboratory experiments using specialized sensors. Finally, the rutting analysis process under triaxial contact stresses during typical driving conditions is established. The results show asphalt pavement exhibits different temperature gradient changes between daytime and nighttime during the summer season. The longitudinal contact stress under braking condition has a significant impact on the longitudinal permanent deformation and compressive creep of asphalt pavement, especially, the longitudinal permanent deformation of the feature points in the middle layer exhibits the most pronounced sensitivity to this contact stress. In addition, the maximal compressive creep is observed at the top of the middle layer, although the characteristic positions for the maximum values of positive and negative creep differ. The proposed new method is beneficial for improving the accuracy and comprehensiveness of asphalt pavement rutting analysis.

Abstract Flowering is a critical step in the plant life cycle. Angelica sinensis (Oliv.) Diels is a medicinal crop whose root is a well-known herbal medicine used in Asia. Early flowering causes changes in secondary metabolic flow and results in the loss of medicinal quality. Based on untargeted metabolomics studies, quinic acid was identified as a metabolite present in significantly higher concentrations during the early-flowering stage in A. sinensis leaves. This metabolite was subsequently investigated as a potential marker for early bolting in A. sinensis under field conditions. Moreover, quinic acid was found to accelerate flowering in the model plant Arabidopsis thaliana. Importantly, the flowering time was delayed in the quinate dehydrogenase At mutant, and this delay was reversed by quinic acid. Quinic acid upregulated the expression of the GA20OX and GID1 receptors and downregulated the expression of the inhibitor DELLA, thereby affecting the levels of FT and LFY and accelerating plant flowering. Quinic acid also significantly changed the expression of genes such as LOX, JAZ1, MYC2 and MYC3 in the jasmonic acid pathway. The trends of GID1, DELLA (GAI) and LOX2 protein expression were essentially consistent with those at the transcription level. These results suggest that quinic acid may promote plant flowering primarily by regulating the expression of genes and proteins in the gibberellin and jasmonic acid pathways.

Abstract Objective Previous observational studies on the association between aspirin use, bone mineral density (BMD), and fracture risk have yielded controversial results. This study explored the causal relationship between aspirin use, BMD, and fracture risk using Mendelian randomization (MR). Methods Summary data for aspirin use and BMD of five different body parts (femoral neck, lumbar spine, forearm, heel, and ultra distal forearm) and fractures were obtained from the integrative epidemiology unit open genome-wide association studies database for bidirectional MR analysis. An appropriate model was chosen based on Cochran's Q test, with inverse variance-weighted as the primary method for MR analysis, supplemented by the weighted-median and MR-Egger methods. MR-Egger and MR-PRESSO were used to test for horizontal pleiotropy and exclude significant outliers that could bias the results. Various sensitivity analyses, including leave-one-out analysis, were conducted to ensure the robustness of the findings. Results Aspirin use significantly increased lumbar spine BMD (odds ratio [OR] = 4.660; 95% confidence interval [CI]: 1.365–15.906; P = 0.014). No significant causal association was found between aspirin use and fracture risk (beta = 59.951; 95% CI: -265.189–385.091; P = 0.718). No significant reverse causality was observed. Conclusion This study indicates that aspirin use does not significantly affect fracture risk but has a significant protective effect on lumbar spine BMD, revealing a potential benefit of aspirin against osteoporosis.

Thrombosis is a leading cause of mortality worldwide. As important gaseous signaling molecules, both nitric oxide (NO) and hydrogen sulfide (H2S) demonstrate antiplatelet and anticoagulant functions, but little attention has been given to their synergistic effect and the underlying mechanism. In the present study, we developed an NO/H2S codelivery system based on enzyme prodrug therapy (EPT) strategy in which the prodrugs are specifically recognized by the engineered β-galactosidase. Targeted codelivery of NO and H2S in vivo was demonstrated by near-infrared fluorescence imaging and confirmed by measuring plasma and tissue levels; as a result, the side effects caused by systemic delivery, such as bleeding time, were reduced. Delivery of an optimized combination of NO and H2S with a low combination index (CI) results in a synergistic effect on the inhibition of platelet adhesion and activation. Mechanistically, NO and H2S cooperatively enhance the cGMP level through redox-based posttranslational modifications of phosphodiesterase 5A (PDE5A), which leads to activation of the cGMP/PKG signaling pathway. Furthermore, targeted codelivery of NO and H2S demonstrates enhanced therapeutic efficacy for thrombosis in two mouse models of FeCl3-induced arterial thrombosis and deep vein thrombosis. Collectively, these results confirm the synergistic efficacy of NO and H2S for antithrombotic therapy, and the codelivery system developed in this study represents a promising candidate for clinical translation.

Abstract Background Oxidative stress plays a crucial role in the pathogenesis of HBV. This study aimed to investigate the value of fibroblast growth factor 21 (FGF21) promoter methylation in the occurrence and development of chronic hepatitis B (CHB) oxidative stress. Methods A total of 241 participants including 221 patients with CHB and 20 healthy controls (HCs) were recruited. Methylation level of FGF21 promoter in peripheral blood mononuclear cells was quantitatively determined. Enzyme-linked immunosorbent assay was used to assess oxidative stress in CHB patients. Results Our study shows that the FGF21 methylation level was significantly lower in HBeAg-positive CHB patients compared to HBeAg-negative CHB patients and HCs (P

Abstract Objective Referring all women who tested positive for human papillomavirus (HPV) 16/18 to colposcopy may lead to potential over-referral issues. Triage tests based on cytology results face challenges in achieving accurate diagnoses. Our study aims to assess the clinical effectiveness of PAX1/JAM3 methylation (CISCER) test as a triage method for HPV 16/18-positive women. Methods From November 2021 to December 2022, a total of 334 women who tested positive for HPV 16/18 and were referred to colposcopy at The Second Affiliated Hospital of Zhejiang University School of Medicine were studied. The clinical utility of the CISCER test, cytology, and the combination of CISCER with cytology as potential triage tests was compared. Results We observed a significant increase in the methylation levels of PAX1 gene and JAM3 gene in women with cervical intraepithelial neoplasia (CIN) grade 2 or severe (CIN2+). The CISCER test demonstrated superior triage performance over cytology, even when used in combination with cytology, showing a high sensitivity of 89.0% (95% confidence interval [CI] 82.9–95.1%) and specificity of 95.3% (95% CI 92.6–98.0%). It achieved an area under the curve of 0.921 (95% CI 0.877–0.966) and an odds ratio of 164.02 (95% CI 68.64–391.95). The immediate CIN2+ risk based on positive CISCER results would be 89.0% (95% CI 80.8–94.1%), with an estimated average of 1.12 referrals needed to detect one CIN2+ case. Moreover, CISCER triaging successfully identified all cancer patients and did not miss any CIN3+ cases among women aged ≥ 30. Conclusions The PAX1/JAM3 methylation detection exhibited excellent accuracy in identifying cervical precancerous lesions in HPV 16/18-positive women and could be considered as a triage tool to reduce excessive referrals for colposcopy and overtreatment.

In order to solve the problem of insufficient strength and electrical conductivity of Cu–Al composites, C18150 Cu/8011 Al/C18150 Cu composites with a thickness of 1.6 mm were fabricated by cast rolling method in this paper, followed by cold rolling and annealing. The interfacial microstructure and precipitation behavior were analyzed through electron backscatter diffraction, scanning electron microscopy, and transmission electron microscopy in detail. The research results show that the three-layer interfaces from the Al layer to the Cu layer are Al2Cu, AlCu, and Al4Cu9, respectively. The interface of the Al layer and Al2Cu layer demonstrate a coherent matching relation, the interface of the Al2Cu layer and AlCu layer shows a semi-coherent matching relation, and the interfaces between AlCu and Al4Cu9, and Al4Cu9 and Cu, are incoherent matching relation. In addition, the Al2Fe3Si4 and Cr precipitations were formed in the composites. The composites exhibit extremely outstanding strength-plasticity-conductivity, and the tensile strength and elongation are 295 MPa and 21%, respectively. The electrical conductivity of the Cu and Al layers is 90.6% and 47.6% according to the International Copper Standard, respectively. This study is useful in guiding the further development and application of high-strength and high-conductivity Cu/Al laminated composites.

Cu/Al laminated composites are a category of structure-function integrated materials with excellent comprehensive performance, but traditional composites prepared using pure Cu and Al are currently facing the problem of insufficient strength. In this paper, C18150Cu and 8011Al were selected to prepare 3.8 mm-thick high strength and high conductivity Cu/Al laminated composites by cast-rolling + cold rolling + annealing. Their interfacial micro-zone microstructures were characterized using SEM, TEM and TKD, and the relationship between their microstructure and performance was explored. The results show that the interfacial structure is a three-layer (Al4Cu9, AlCu, Al2Cu) alternating with a two-layer (Al4Cu9, Al2Cu) interface of intermetallic compounds. This particular interfacial layer structure can be attributed to the fact that when the cold-rolled fracture interface regrows at a heat treatment temperature of 320 °C, the banded Cr precipitation zone near the interface hinders the diffusion of the Cu element and locally thins the interface thickness. In addition, the presence of nano and submicron Cr phases, nano Cu5Zr phases, and twinned crystals on the Cu side of the near-interfacial micro-zone. By efficiently utilizing the properties of C18150Cu and by having a relatively reasonable interface thickness after heat treatment. The composites in this study exhibit more advantageous mechanical properties compared to other reports.

目的 采用光学相干断层扫描血管成像（optical coherence tomography angiography，OCTA）技术，探讨颈内动脉狭窄（internal carotid artery stenosis，ICAS）患者黄斑区微血管特征及其与血管狭窄的相关性。 方法 连续纳入2023年1月—2024年9月西安市第一医院（西北大学附属第一医院）神经内科和神经眼科收治的经血管评估确诊的ICAS患者，按狭窄侧别、程度分别进行分组，并纳入年龄、性别、既往史等相匹配的参与者为健康对照组。对研究对象进行黄斑区OCTA检查，并收集其小血管密度、血管密度、灌注面积、脉络膜层大中血管血管容积及血管指数等数据进行组间比较。 结果 本研究共纳入66例研究对象，其中单侧ICAS组20例、双侧ICAS组26例、健康对照组20例，男性54例（81.8%），平均年龄为（67.5±8.7）岁。3组间除既往卒中或TIA病史外，其他临床特征差异均无统计学意义。单侧ICAS组与健康对照组相比，双眼脉络膜毛细血管层灌注面积低于健康对照组，但单侧ICAS患者双眼间各指标差异均无统计学意义。双侧ICAS组与健康对照组相比，浅层血管复合体小血管密度、视网膜内层灌注面积、脉络膜毛细血管层灌注面积、视网膜内层血管密度、浅层血管复合体血管密度差异均有统计学意义（P0.05）。所有ICAS狭窄侧眼按狭窄程度分为中度及以下狭窄组（31只）、重度及以上狭窄组（41只），与健康对照组3组进行比较，发现浅层血管复合体小血管密度、脉络膜毛细血管层灌注面积、视网膜内层血管密度及浅层血管复合体血管密度差异均具有统计学意义（P0.05）。 结论 ICAS患者黄斑区微血管指标较健康对照组参与者降低，一侧ICAS病变可导致双眼黄斑区微循环受损，且受狭窄程度影响。 Abstract: Objective To explore the microvascular characteristics of the macular lutea in patients with internal carotid artery stenosis (ICAS) and their correlation with vascular stenosis using optical coherence tomography angiography (OCTA). Methods Patients diagnosed with ICAS through vascular assessment, who were admitted to the Department of Neurology and Neuro-Ophthalmology at The First Hospital of Xi’an (The First Affiliated Hospital of Northwest University) from January 2023 to September 2024, were consecutively included. Patients were grouped according to the lesion side and stenosis degree. Age, gender, and medical history-matched participants were included as a healthy control group. OCTA examinations were conducted in the macular lutea for the enrolled subjects, and the data of small vessel density, vessel density, perfusion area, volume of medium to large choroidal vessels, and vascular index were all collected for inter-group comparison. Results A total of 66 subjects were included in this study, including 20 cases in the unilateral ICAS group, 26 cases in the bilateral ICAS group, and 20 cases in the healthy control group. Among them, 54 (81.8%) were male, with an average age of (67.5 ± 8.7) years. There were no statistically significant differences in clinical characteristics among the three groups, except for the history of previous stroke or TIA. Compared with the healthy control group, the perfusion area of the choroidal capillary layer in both eyes of the unilateral ICAS group was lower than that of the healthy control group. However, there were no statistically significant differences in these indicators between both eyes of the unilateral ICAS patients. Compared with the healthy control group, there were statistically significant differences in the small vessel density of the superficial vascular complex, the perfusion area of the inner retinal layer, the perfusion area of the choroidal capillary layer, the vessel density of the inner retinal layer, and the vessel density of the superficial vascular complex in the bilateral ICAS group (P0.05). All eyes with ICAS were divided into moderate and below (31 cases) and severe and above (41 cases) stenosis groups. When comparing these two groups with the healthy control group, it was found that the differences in small vessel density of the superficial vascular complex, the perfusion area of the choroidal capillary layer, the vessel density of the inner retinal layer, and the vessel density of the superficial vascular complex were statistically significant (P0.05). Conclusions In ICAS patients, microvascular indicators in the macular lutea were reduced compared to those in the healthy control group. Unilateral ICAS lesions can lead to impaired macular microcirculation in both eyes, with the degree of impairment influenced by the severity of stenosis.

Abstract Background Atypical squamous cells of undetermined significance (ASC-US) often present diagnostic challenges with cytology-based results, leading to potential underdiagnosis or overdiagnosis. An effective triage method is essential for managing these cases to reduce unnecessary referrals and treatment. Methods A total of 322 women diagnosed with ASC-US were tested for HPV-DNA and the PAX1 and JAM3 methylation (PAX1 m /JAM3 m ) test in the study. Results Methylation levels of PAX1 and JAM3 were significantly elevated in cervical lesions classified as CIN2 or more severe lesions (CIN2+). The methylation assay demonstrated a sensitivity of 83.8% and a specificity of 95.8%, outperforming HPV-DNA testing in differentiating high-grade cervical lesions among women with ASC-US. Moreover, PAX1 m /JAM3 m testing significantly reduced the colposcopy referral rate for further diagnostic procedures in high-risk HPV-positive women by 79.5%. Conclusions PAX1 m /JAM3 m testing shows promise as a reliable supplemental method to HPV-DNA testing for the triage of women with cytologic ASC-US. In addition, the molecular triage based on the CISCER assay or single PAX1 or JAM3 methylation, had better effects in the women with non-HPV16/18 group. This approach could potentially minimize overtreatment and unnecessary referrals in clinical practice, enhancing patient management and resource utilization.

Background/Aims: Identifying novel therapeutic targets for hepatitis B virus (HBV)-induced hepatocellular carcinoma (HCC) has become a key goal in liver cancer research. Even though long non-coding RNAs (lncRNAs) do not code proteins, they could regulate the expression of functional genes and thus mediate disease development. The aim of this study was to estimate the role of lncRNA POLR2J4 (POLR2J4) in the progression of hepatitis B virus-related hepatocellular carcinoma (HBV–HCC) to pinpoint a potential biomarker. Materials and Methods: This study included 109 patients diagnosed with HBV-positive HCC, from whom tissue samples were collected. The expression level of POLR2J4 was evaluated by qPCR. The significance of POLR2J4 in HBV–HCC development and prognosis was estimated by Chi-square, Kaplan-Meier, and Cox analysis. In vitro, POLR2J4 was regulated in HBV–HCC cells, and its effect on cell growth and metastasis was assessed by CCK8 and Transwell assay. The interaction between POLR2J4 and miR-214-3p was evaluated through the luciferase reporter and RNA immunoprecipitation assays. Results: In tumor tissues of HBV–HCC patients, there was an observed increase in the expression of POLR2J4. The increase was closely related with patients’ presence of cirrhosis and vascular invasion, higher AFP, and advanced Edmondson grade and TNM stage. An upregulation of POLR2J4 predicted a poor prognosis for HBV–HCC patients and served as an independent indicator. In HBV-related HCC cells, silencing POLR2J4 suppressed cell proliferation, migration, and invasion. Furthermore, POLR2J4 negatively regulated miR-214-3p reversing the inhibition of cellular processes. Conclusion: POLR2J4 acted as a prognostic biomarker and a tumor promoter of HBV–HCC by modulating miR-214-3p.

Anthropogenic land greening is a vital strategy to combat the global warming crisis. However, the changing external environment and endowment factors may constrain the effectiveness of land greening. It remains unclear how to quantify and optimize land greening strategies scientifically. This article reviewed the theoretical foundations of land greening, pointing out that climate governance and human settlement quality improvement have gradually become the two core objectives of land greening since the 20th century. Multi-source and multi-scale experimental and observational surveys are important techniques for detecting and evaluating long-term land greening in the context of climate change, especially by forming experimental and observational networks. The theoretical mechanisms of interactions among climate, humans, and vegetation were also explored. For modeling approaches, hybrid modeling based on Earth system coupling theory may be the most promising but challenging approach. Four main challenges of scientific land greening were also discussed, including knowledge gaps related to land greening mechanisms, unclear multifaceted effects of land greening, lack of forward-looking quantitative assessment, and difficulties in evaluating synergies and trade-offs among assessment targets. Based on these, a strategic framework was proposed, including systematic observation, mechanism research, expectation assessment, and scientific planning for scientific greening programs in the Guangdong–Hong Kong–Macao Greater Bay Area. This review underscored the importance of proactively implementing land greening programs and provided guidelines for scientific greening based on cutting-edge theory and methods.

Background/purpose: Root canal irrigants are difficult to diffuse deep into the dentinal tubules for root canal disinfection. The purpose of this study was to assess the ability of different diffusing enhancers to deliver chlorhexidine (CHX) into dentinal tubules. Materials and methods: The diffusing property of five diffusing enhancers (acetone, DMSO, Triton X-100, JFC-E and azone) into dentinal tubules was firstly assessed using the Rhodamine B. The ability of the diffusing enhancers to deliver CHX into dentinal tubules was then evaluated both qualitatively and quantitatively. A deep dentinal tubule Enterococcus faecalis infection model was further established to test the bactericidal effect of CHX delivered by different diffusing enhancers. Finally, the in vitro cytotoxicity of these diffusing enhancers was tested using the CCK-8 method. Results: Azone, Triton X-100 and JFC-E exhibited the largest maximum diffusing depths at all root canal parts (P

Abstract To determine the characteristics of posterior precortical vitreous pockets (PPVPs) and to observe vitreous changes in myopic eyes by swept-source optical coherence tomography (SS-OCT) and en face imaging in a cohort of the Chinese Han population. This was a cross-sectional study. Volunteers (235 participants, 374 eyes) received an SS-OCT examination. The heights and widths of the PPVPs were measured by SS-OCT. The area of the PPVPs was measured on en face images. The relationships between PPVP size and sex, age, axial length (AL) and spherical equivalent (SE) were evaluated. The mean width and height were 6711.64 ± 1241.87 μm and 662.47 ± 326.39 μm, respectively. The area of the PPVPs was 30.296 ± 9.114 mm2. Boat-shaped, oval, and hook-shaped PPVPs were observed in 73.26%, 21.12%, and 5.62% of all eyes, respectively; 73.53% of all PPVPs had channels communicating with Cloquet’s tubes. There was a significant difference in the PPVP width among the participates over and under 50 years old (t = -2.508, P = 0.031). Age had a positive correlation with the PPVP width (r = 0.53, P = 0.001). The PPVP height showed significant differences among the different myopia groups (F = 3.618, P = 0.013). SE had a negative correlation with the PPVP height (r = -0.176, P = 0.001). However, there were no correlations between the AL and the width, height or area of the PPVPs (P = 0.117; P = 0.334; P = 0.057, respectively). Age and myopia affect the size of PPVPs. SS-OCT greatly facilitates visualization of the complex structure of the vitreous.

Highlights NaTFSI/SUL:OTE:FEC facilitates the formation of S, N-rich, dense and robust cathode–electrolyte interphase on NaNMF cathode, which improves the cycling stability under high voltage. By utilizing NaTFSI/SUL:OTE:FEC, the Na||NaNMF batteries achieved an impressive retention of 81.15% after 400 cycles at 2 C with the cutoff voltage of 4.2 V. The study offers a reference for the utilization of sulfolane-based electrolytes in sodium-ion batteries (SIBs), while the nonflammability of the NaTFSI/SUL:OTE:FEC enhances the safety of SIBs.

Abstract Background Harsh parenting has been recognized as a risk factor for adolescent anxiety; however, the underlying mechanisms of this relationship remain unclear, and it is unknown whether this relationship is influenced by different parental roles and living arrangements. This study aimed to investigate the mediating mechanisms between harsh parenting and adolescent anxiety symptoms using a multiple mediation model and to further compare specific roles of harsh parenting and distinguish between the living arrangements. Methods A total of 3505 adolescents completed this survey, and 3295 adolescents (54.7% girls, Mage = 14.97 years) were included in the study. Participants completed self-assessments measuring harsh parenting, self-efficacy, school connectedness, Internet addiction, sleep problems, and anxiety. They were categorized into three groups based on living arrangements: living with both parents, only with the mother, or only with the father. Results Correlational analyses revealed that both maternal and paternal harsh parenting were associated with increased anxiety symptoms. Structural equation modeling (SEM) mediation analyses and multigroup analyses showed that the independent mediating effects of school connectedness, Internet addiction, and sleep problems, as well as the sequential mediating pathways involving self-efficacy → school connectedness, self-efficacy → Internet addiction, and self-efficacy → sleep problems, vary across the adolescents’ living arrangements in the association between maternal and paternal harsh parenting and adolescent anxiety symptoms. Conclusions This study elucidated the mechanisms linking harsh parenting to adolescent anxiety symptoms and validated the effects of different parental roles and living arrangements. The findings provide important insights for developing targeted interventions to address anxiety symptoms in adolescents exposed to harsh parenting.

Abstract Candida tropicalis (C. tropicalis) is a zoonotic pathogen that is widespread in the environment and in recent years an increasing number of dairy cows have been infected with the fungus causing mastitis in cows.In this study, 37 milk samples from the udders of cows with clinical mastitis were collected from a dairy farm in Guangxi Province, China, from which C. tropicalis was isolated and identified, and then the isolated fungi were subjected to genome frame map sequencing, genome functional analysis as well as comparative genome analysis of the sequencing results, and combined with the virulence test of the fungi and drug sensitivity test of the fungi determined in infected mice, the resistance genes and pathogenicity of the fungi were Analysis of resistance genes and pathogenicity.Our study results revealed the isolation and characterisation of C. tropicalis from diseased cows, with a genome length of approximately 14.27 Mb. Functional annotation of the genome identified 4068 genes associated with C. tropicalis. The strain exhibited a chemoresistance mutation in the gene cyp51,a virulence-enhancing mutation in the gene VTC4, and mutations in genes linked to drug resistance. Pathogenicity tests demonstrated that C. tropicalis could induce damage to the internal organs of mice, leading to different levels of cyanosis in the abdominal cavity, white necrotic foci on the surface of internal organs, lung hemorrhage, and enlargement of the spleen and thymus.Histological sections also revealed varying degrees of hemorrhage and degenerative changes in the cells of different organs in the mice. Drug sensitivity tests showed that the fungus was highly sensitive to nystatin and ketoconazole, moderately sensitive to amphotericin B, and insensitive to antibiotics such as itraconazole, gentamicin, and penicillin. In conclusion, C. tropicalis isolated from dairy cows in the Guangxi region in this study was pathogenic and resistant to azoles such as itraconazole and fluconazole, and this study provides a theoretical basis for the further screening of novel resistance genes in C. tropicalis, as well as providing a certain reference for the drugs used for the treatment of fungal cow mastitis in this region.

Central precocious puberty secondary to Leydig cell tumors is rare in children. We retrospectively analyzed the mid- to long-term follow-up data of patients with Leydig cell tumors. The clinical data of 12 consecutive patients who were treated at Beijing Children’s Hospital, Capital Medical University (Beijing, China), between January 2016 and October 2023 were retrospectively reviewed. Clinical evaluations, including physical examination, hormone examination, serum tumor marker analysis, abdominal and scrotal ultrasound, chest X-ray, and bone age measurement, were conducted before surgery and at follow-up time points. Surgical approaches were selected according to the individual conditions. Patients with an abnormal hormonal status and suspected of having central precocious puberty were referred to endocrinologists to confirm the diagnosis. Subsequently, gonadotropin-releasing hormone analog therapy was proposed. The mean patient age was 81.3 (range: 40–140) months at the time of the operation. Ten patients had peripheral precocious puberty at admission. All patients had elevated preoperative testosterone levels, whereas tumor marker levels were normal. Testis-sparing surgery was performed in eleven patients, and radical orchiectomy was performed in one patient. The follow-up duration (mean ± standard deviation) was 36.2 ± 25.3 months. Five patients had central precocious puberty, with a mean duration of 3.4 (range: 1–6) months postoperatively. Three patients were receiving gonadotropin-releasing hormone analog therapy, and good suppression of puberty was observed. No risk factors were found for secondary central precocious puberty. There was a high prevalence of central precocious puberty secondary to Leydig cell tumors in our study. Gonadotropin-releasing hormone analog therapy has satisfactory treatment effects. Larger sample sizes and long-term follow-up are needed in future studies.

BackgroundThe relationship between abnormal renal function and serum uric acid levels in patients with acute ischemic stroke (AIS) remains insufficiently explored. Although uric acid is associated with cardiovascular and cerebrovascular risk, the specific link between normalized serum uric acid (SUA/SCr) and stroke recurrence in patients with impaired renal function has not been well studied. This study aims to fill this gap by investigating the association between SUA/SCr and 1-year stroke recurrence in patients with AIS and abnormal renal function.MethodsThis study utilized the ratio of serum uric acid (SUA) to serum creatinine (SCr) to represent SUA levels normalized for renal function. Abnormal Renal function was defined by the estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m2. Multivariable Cox regression, curve fitting, and stratified analyses were employed to assess the relationship between SUA/SCr and 1-year stroke recurrence in patients with AIS and abnormal renal function, considering SUA/SCr as both a continuous variable and in quartiles (Q1–Q4).ResultsOf 1,932 enrolled patients (65.3% male; mean age 66.7 ± 11.3 years), each unit of increase in SUA/SCr was associated with a 17% decrease in 1-year stroke recurrence (HR = 0.83, 95% CI 0.73 to 0.96, P = 0.009). Compared to Q1, the Q2 and Q4 groups showed significantly reduced risk in 1-year stroke recurrence (Q2: HR = 0.46, 95% CI 0.27 to 0.79, P = 0.005; Q4: HR = 0.47, 95% CI 0.27 to 0.81, P = 0.007), with a significant trend across all quartiles (P = 0.01 for trend tests). Curve fitting revealed a negative but non-linear correlation. Subgroup analyses showed that in patients with eGFR < 60 ml/min/1.73 m2, Q4 had significantly lower 1-year stroke recurrence risk than Q1 (HR = 0.19, 95% CI 0.04 to 0.86, P = 0.031).ConclusionLow SUA/SCr independently predicts 1-year stroke recurrence in patients with AIS and abnormal renal function, particularly in those with eGFR < 60 mL/min/1.73 m2.

Abstract EED (embryonic ectoderm development) is a core subunit of the polycomb repressive complex 2 (PRC2), which senses the trimethylation of histone H3 lysine 27 (H3K27). However, its biological function in cerebellar development remains unknown. Here, we show that EED deletion from neural stem cells (NSCs) or cerebellar granule cell progenitors (GCPs) leads to reduced GCPs proliferation, cell death, cerebellar hypoplasia, and motor deficits in mice. Joint profiling of transcripts and ChIP‐seq analysis in cerebellar granule cells reveals that EED regulates bunches of genes involved in cerebellar development. EED ablation exhibits overactivation of a developmental repressor long non‐coding RNA H19. Importantly, an obvious H3K27ac enrichment is found at Ctcf, a trans‐activator of H19, and H3K27me3 enrichment at the H19 imprinting control region (ICR), suggesting that EED regulates H19 in an H3K27me3‐dependent manner. Intriguingly, H19 deletion reduces EED expression and the reprogramming of EED‐mediated H3K27me3 profiles, resulting in increased proliferation, differentiation, and decreased apoptosis of GCPs. Finally, molecular and genetic evidence provides that increased H19 expression is responsible for cerebellar hypoplasia and motor defects in EED mutant mice. Thus, this study demonstrates that EED, H19 forms a negative feedback loop, which plays a crucial role in cerebellar morphogenesis and controls cerebellar development.

ObjectiveThis study aims to assess the diagnostic efficacy of a combined approach integrating chromosomal karyotyping, copy number variation sequencing (CNV-seq), and quantitative fluorescence polymerase chain reaction (QF-PCR) in detecting chromosomal abnormalities in high-risk pregnancies.MethodsThis retrospective study analyzed 617 high-risk pregnancies undergoing prenatal diagnosis from February 2023 to August 2024, with amniotic fluid samples concurrently analyzed using karyotyping, CNV-seq, and QF-PCR. We evaluated clinical characteristics, diagnostic yields, and inter-method concordance rates. Longitudinal follow-up assessed pregnancy outcomes and neonatal phenotypes, with particular emphasis on cases demonstrating diagnostic discrepancies or variants of uncertain clinical significance.ResultsThe integrated approach detected chromosomal abnormalities in 12.5% (77/617) of cases, significantly higher than the rates achieved by karyotyping alone (9.7%) and CNV-seq/QF-PCR alone (8.3%) (p < 0.05). Karyotyping showed full concordance with CNV-seq and QF-PCR in detecting major chromosomal aneuploidies, identifying 21 cases of trisomy 21 and 4 cases of trisomy 18. CNV-seq uniquely identified additional pathogenic copy number variations in 2.1% of cases and variants of uncertain significance (VUS) in 3.2% of cases, both undetectable by conventional karyotyping. Subjects with high-risk non-invasive prenatal testing (NIPT) results had the highest abnormality detection rate (57.6%, p < 0.05). Follow-up data revealed pregnancy termination in 44 of 97 cases with chromosomal abnormalities. Notably, neonates carrying pathogenic CNVs inherited from asymptomatic parents demonstrated normal phenotypes.ConclusionThe integration of karyotyping, CNV-seq, and QF-PCR provides superior diagnostic yield compared to individual testing strategies in high-risk pregnancies. Although karyotyping remains the gold standard for detecting major chromosomal aberrations, CNV-seq and QF-PCR enhance diagnostic precision through detection of submicroscopic variations. Multi-center studies with larger cohorts are needed to confirm these findings and clarify the clinical significance of uncertain variants.

Abstract Factor XII (FXII) is the zymogen of the plasma protease FXIIa that activates the intrinsic coagulation pathway and the kallikrein kinin-system. The role of FXII in inflammation has been obscure. Here, we report a single-domain antibody (nanobody, Nb) fused to the Fc region of a human immunoglobulin (Nb-Fc) that recognizes FXII in a conformation-dependent manner and interferes with FXIIa formation. Nb-Fc treatment inhibited arterial thrombosis in male mice without affecting hemostasis. In a mouse model of extracorporeal membrane oxygenation (ECMO), FXII inhibition or knockout reduced thrombus deposition on oxygenator membranes and systemic microvascular thrombi. ECMO increased circulating levels of D-dimer, alkaline phosphatase, creatinine and TNF-α and triggered microvascular neutrophil adherence, platelet aggregation and their interaction, which were substantially attenuated by FXII blockade. Both Nb-Fc treatment and FXII knockout markedly ameliorated immune complex-induced local vasculitis and anti-neutrophil cytoplasmic antibody-induced systemic vasculitis, consistent with selectively suppressed neutrophil migration. In human blood microfluidic analysis, Nb-Fc treatment prevented collagen-induced fibrin deposition and neutrophil adhesion/activation. Thus, FXII is an important mediator of inflammatory responses in vasculitis and ECMO, and Nb-Fc provides a promising approach to alleviate thrombo-inflammatory disorders.

Abstract Disulfidptosis, the newest form of programmed cell death, is closely associated with the immune microenvironment of cancer cells. Long non-coding RNA (lncRNA) has also been found to play a crucial role in melanoma. However, the role of disulfidptosis-related lncRNA in melanoma remains unclear. Through bioinformatic analysis of the transcriptional, clinical, and pathological data from the TCGA-SKCM (The Cancer Genome Atlas—Skin cutaneous melanoma) database, we established a 2-Disulfidptosis-related lncRNA (DRL) prognostic model and a novel molecular subtype for melanoma. The survival and ROC curves of the 2-DRL prognostic model demonstrated its strong efficacy in predicting the prognosis of melanoma. The high-risk group of melanoma exhibited a significant decrease in ESTIMATEScore, ImmuneScore, and StromalScore, indicative of pronounced immune suppression and exhaustion. Subgroup C2 of melanoma displayed an immune-activated state, while subgroups C1 and C3 showed immune suppression and exhaustion, potentially leading to poorer prognosis. Subgroup C1 demonstrated better sensitivity to Zoledronate, UMI-77, Nilotinib, and Cytarabine. Subgroup C2 exhibited greater sensitivity to Ribociclib, XAV939, Topotecan, and Ruxolitinib. Subgroup C3 showed higher sensitivity to VX-11e, Ulixertinib, Trametinib, and Afatinib. This study revealed the immune microenvironment status and targeted drug sensitivity in melanoma patients with different risk scores and molecular subtypes, offering valuable guidance for clinical treatment and identifying significant DRL targets for future in-depth research.

Initiating from omics, the research aimed to discover and filter oat active peptides effective against hyperuricemia, and to study the operational mechanism of these oat active peptides in treating hyperuricemia. In the present study, RNA was extracted from oat grains for high-throughput transcriptomic sequencing, and oat grain protein sequences were acquired by comparing with a reference genome and quantifying the expression of protein-coding genes. Active components of oat peptides were selected by employing high-throughput enzymolysis in silico, Peptide Ranker, and ADME/T. Network pharmacology were utilized to discover active peptides from oat proteins that were effective against hyperuricemia. The findings indicated that for 'Bayou No.1' and 'Baiyan No.7' oat grains, the counts of protein sequences expressed with under 90% repeatability during the grain formation and grain-filling phases were respectively 6310, 3157, and 5804, 5107. The optimal peptide library was from the protein sequences of 'Bayou No.1' naked oat in the grain-filling stage, processed through simulated enzymatic digestion in silico with proteinase K, yielding a library with 42 oat active peptides predicted to have potential activity and favorable pharmacological properties. The initial screening revealed key oat active peptides sequences against hyperuricemia to be PPF, PPPL, MPF, MPL, and PPPF, potentially targeting genes like ALB, IL1B, SRC, CASP3, and STAT3, influencing pathways in cancer, lipid and atherosclerosis, and chemically induced carcinogenesis-receptor activation to mitigate hyperuricemia. Molecular docking showed that binding energy

Abstract Despite the potential of small molecules and recombinant proteins to enhance the efficiency of homology-directed repair (HDR), single-stranded DNA (ssDNA) donors, as currently designed and chemically modified, remain suboptimal for precise gene editing. Here, we screen the biased ssDNA binding sequences of DNA repair-related proteins and engineer RAD51-preferred sequences into HDR-boosting modules for ssDNA donors. Donors with these modules exhibit an augmented affinity for RAD51, thereby enhancing HDR efficiency across various genomic loci and cell types when cooperated with Cas9, nCas9, and Cas12a. By combining with an inhibitor of non-homologous end joining (NHEJ) or the HDRobust strategy, these modular ssDNA donors achieve up to 90.03% (median 74.81%) HDR efficiency. The HDR-boosting modules targeting an endogenous protein enable a chemical modification-free strategy to improve the efficacy of ssDNA donors for precise gene editing.

Abstract Objectives In this study, we aimed to validate the performance of the PAX1 and JAM3 methylation (PAX1 m /JAM3 m ) test as a triage tool for detecting cervical intraepithelial neoplasia grade 3 or worse (CIN3 +) in non-16/18 high-risk human papillomavirus-positive patients (non-16/18 hrHPV +). Methods The triage performance of liquid-based cytology (LBC) and the PAX1 m /JAM3 m test for detecting CIN3 + were compared. Results In total, 1851 participants had cervical histological outcomes and were included in the analysis. The sensitivity/specificity of the LBC test results with atypical squamous cells of undetermined significance or worse (LBC ≥ ASCUS) and the PAX1 m /JAM3 m test were 90.1%/26.7% and 84.8%/88.5%, respectively. PAX1 m /JAM3 m ( +) had the highest diagnostic AUC (0.866, 95% confidence interval (CI) 0.837–0.896) in the whole cohort. All cancers (n = 20) were detected by PAX1 m /JAM3 m (+). Compared with LBC ≥ ASCUS, PAX1 m /JAM3 m (+) reduced the number of patients who needed referral for colposcopy by 57.21% (74.66% vs. 17.45%). The odds ratios for detecting CIN3 + by LBC ≥ ASCUS and PAX1 m /JAM3 m (+) were 3.3 (95% CI 2.0–5.9) and 42.6 (27.1–69.6), respectively (p

Abstract Premature ovarian failure (POF), which is often comorbid with dry eye disease (DED) is a key issue affecting female health. Here, we explored the mechanism underlying comorbid POF and DED to further elucidate disease mechanisms and improve treatment. Datasets related to POF (GSE39501) and DED (GSE44101) were identified from the Gene Expression Omnibus (GEO) database and subjected to weighted gene coexpression network (WGCNA) and differentially expressed genes (DEGs) analyses, respectively, with the intersection used to obtain 158 genes comorbid in POF and DED. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses of comorbid genes revealed that identified genes were primarily related to DNA replication and Cell cycle, respectively. Protein–Protein interaction (PPI) network analysis of comorbid genes obtained the 15 hub genes: CDC20, BIRC5, PLK1, TOP2A, MCM5, MCM6, MCM7, MCM2, CENPA, FOXM1, GINS1, TIPIN, MAD2L1, and CDCA3. To validate the analysis results, additional POF- and DED-related datasets (GSE48873 and GSE171043, respectively) were selected. miRNAs-lncRNAs-genes network and machine learning methods were used to further analysis comorbid genes. The DGIdb database identified valdecoxib, amorfrutin A, and kaempferitrin as potential drugs. Herein, the comorbid genes of POF and DED were identified from a bioinformatics perspective, providing a new strategy to explore the comorbidity mechanism, opening up a new direction for the diagnosis and treatment of comorbid POF and DED.

Abstract Background During the 14th Five-Year Plan, China aims to transform rural migrants into urban citizens and ensure equal access to public services to enhance new urbanization. Understanding migrant workers' settlement intentions is crucial for their citizenship development. Based on the fundamental role of the right to life and health, equalization of basic public health services is essential. Therefore, understanding the potential impact of public health services equalization on the settlement intention of migrant workers is crucial in China’s new urbanization. Method In this study, we utilized data from the 2017 wave of China Migrants Dynamic Survey (CMDS) and employed the Propensity Score Matching method to investigate the impact of basic public health service equalization policy on the settlement intention of migrant workers. Additionally, we utilized the Mediation Effect Model to uncover the impact mechanism. Results Our findings indicate that basic public health service equalization policy has a significant positive effect on increasing the settlement intention of migrant workers, with an even greater effect observed among the low-income group, the cross-provincial subsample, and the new generation subsample. The results of the Mediation Effect Model suggest that Basic public health service equalization policy can bolster the subjective integration willingness and subjective identity of migrant workers, thereby enhancing their settlement intention. Conclusion Based on the results, we propose to strengthen the promotion of the basic public health service equalization policy and expand the coverage of health records to further increase the settlement intention of migrant workers.

Background: Existing studies have revealed functional abnormalities in certain brain regions of patients with schizophrenia (SZ), but the relationships between these abnormalities and their impact on disease progression remain unclear. Methods: Fifty-six patients with SZ and 56 healthy controls were included. Based on resting-state functional magnetic resonance imaging, we analyzed fractional amplitude of low-frequency fluctuations (fALFF), regional homogeneity (ReHo), and degree centrality (DC). Statistically significant metrics were selected as features, and machine learning models were used to distinguish between patients and controls. Analyze the importance of features in the optimal model. The Louvain community detection algorithm and structural equation modeling were used to investigate community relationships and potential causal effects. Results: The average prediction accuracy of various ML classifiers reached 0.9241 by fALFF, ReHo, and DC values. The SVM model have the highest performance with an accuracy of 0.9464. Abnormal ReHo in the right middle frontal gyrus contributed most to this optimal classifier and participated in the direct impact on SZ. All the features we analyzed ultimately constituted two functional clusters (FClus), which exhibit internal causal influences. FClus1 had a positive influence on SZ, with the cascade starting from abnormal fALFF in the right inferior temporal gyrus. FClus2 had a negative influence on SZ, with the cascade starting from abnormal fALFF in the left fusiform gyrus.Abnormal fALFF in the right caudate nucleus, degree centrality in the right angular gyrus, and ReHo in the right lentiform nucleus do not have a causal impact on the disease. Conclusions: We identified interactions among features within FClus that potentially influence the onset and progression of schizophrenia, including epicenter phenomenon of FClus, FClus for inhibiting schizophrenia, and abnormal function of brain regions without direct impact. Additionally, we believe that the contribution of features to the disease classification model may indicate the size of their direct impact on the disease, not necessarily their importance in the disease process.

We recruited a healthy 44-year-old female and obtained her skin fibroblasts. Subsequently, the induced pluripotent stem cell line was successfully established using non-integrated reprogramming technology. The cell line had a normal karyotype and has been confirmed to have good pluripotency through the detection of pluripotency markers and detection of teratoma formation. This cell line can serve as an effective control for studying the cellular pathological mechanisms of other specific mutations.

Study region: Xiangjiang River basin, is at the middle and lower Yangtze River. Study focus: Increasing evidence shows that large-scale climate indices are being linked to the spatio-temporal evolution of extreme flood events in many regions. It is widely recognized that identifying the response of flood risks to climate factors is investigated by nonstationary local hydrological frequency analysis (NLFFA). However, high uncertainty by utilizing NLFFA usually cannot achieve the accuracy for engineering design, creating need for nonstationary regional flood frequency analysis (NRFFA) for reducing uncertainty. This study presents a NRFFA for extreme flood risk under changing environment that is conditioned on the large-scale climate index. The nonstationary regional analysis is developed in a hierarchical Bayesian framework to support partial and full pooling, which can enhance climate-based regionalization skill as well as retain site-specific characteristics. Simultaneously, the modeling structure is designed to consider the spatial dependence across the basin. New hydrological insights for the region: Regional models for whole basin and climatically homogeneous sub-region respectively, and local models are compared: the regional models exhibit a great benefit with the estimates uncertainty reduction and allows a better quantification of large-scale climate effect on flood extremes. Moreover, the regional partial pooling model for homogeneous sub-region indicate that the regional model can be further improved by considering a prior pooling stations formed by similar significant climate response.