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Abstract Background The prognosis of colon cancer (CC) is challenging to predict due to its highly heterogeneous nature. Ferroptosis, an iron-dependent form of cell death, has roles in various cancers; however, the correlation between ferroptosis-related genes (FRGs) and prognosis in CC remains unclear. Methods The expression profiles of FRGs and relevant clinical information were retrieved from the Cancer Genome Atlas (TCGA) database. Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) regression model were performed to build a prognostic model in TCGA cohort. Results Ten FRGs, five of which had mutation rates ≥ 3%, were found to be related to the overall survival (OS) of patients with CC. Patients were divided into high- and low-risk groups based on the results of Cox regression and LASSO analysis. Patients in the low-risk group had a significantly longer survival time than patients in the high-risk group (P < 0.001). Enrichment analyses in different risk groups showed that the altered genes were associated with the extracellular matrix, fatty acid metabolism, and peroxisome. Age, risk score, T stage, N stage, and M stage were independent predictors of patient OS based on the results of Cox analysis. Finally, a nomogram was constructed to predict 1-, 3-, and 5-year OS of patients with CC based on the above five independent factors. Conclusion A novel FRG model can be used for prognostic prediction in CC and may be helpful for individualized treatment.

Abstract Background Blood counting and the liver function tests, as the routine examinations, can reflect the immune and nutritional status of the body, our aim is to assess the prognostic significance of serum gamma-glutamyltransferase (GGT) levels and AST/ALT in primary hepatic carcinoma. Methods Clinico-pathological data of 414 patients with primary hepatic carcinoma in the 1st Affiliated Hospital of Anhui Medical College between January 2007 to January 2014 was analyzed retrospectively in this study. Survival curves were described by Kaplan-Meier method and compared by Log-rank test, univariate and multivariate analysis were used to identify the prognostic factors. Results GGT was positively correlated with the tumor size(P = 0.000), tumor volume (P = 0.000), tumor volume percent (P = 0.004), TNM stage(P = 0.009), 1-year survival rate (P = 0.000), 3- years survival rate (P = 0.000) and 5-years survival rate(P = 0.000). The serum ALT/AST was significantly correlated with age (P = 0.047), tumor size(P = 0.002), tumor volume (P = 0.010), tumor volume percent (P = 0.005), TNM stage(P = 0.006), liver cirrhosis(P = 0.003), 3- years survival rate (P = 0.032) and 5-years survival rate(P = 0.000). The Kaplan-Meier curves showed that the patients with primary hepatic carcinoma had a longer time in the low GGT group and low AST/ALT group, showing a significant difference (P

BackgroundThe prognosis of patients with hepatocellular carcinoma (HCC) remains difficult to accurately predict. The purpose of this study was to establish a prognostic model for HCC based on a novel scoring system.MethodsFive hundred and sixty patients who underwent a curative hepatectomy for treatment of HCC at our hospital between January 2007 and January 2014 were included in this study. Univariate and multivariate analyses were used to screen for prognostic risk factors. The nomogram construction was based on Cox proportional hazard regression models, and the development of the new scoring model was analyzed using receiver operating characteristic (ROC) curve analysis and then compared with other clinical indexes. The novel scoring system was then validated with an external dataset from a different medical institution.ResultsMultivariate analysis showed that tumor size, portal vein tumor thrombus (PVTT), invasion of adjacent tissues, microvascular invasion, and levels of fibrinogen and total bilirubin were independent prognostic factors. The new scoring model had higher area under the curve (AUC) values compared to other systems, and the C-index of the nomogram was highly consistent for evaluating the survival of HCC patients in the validation and training datasets, as well as the external validation dataset.ConclusionsBased on serum markers and other clinical indicators, a precise model to predict the prognosis of patients with HCC was developed. This novel scoring system can be an effective tool for both surgeons and patients.

Background: The prognostic prediction after radical resection of pancreatic ductal adenocarcinoma (PDAC) has not been well-established. We aimed to establish a prognostic model for PDAC based on a new score system, which included a clinical routine serum marker.Methods: A total of 438 patients who underwent curative PDAC at the First Affiliated Hospital of Anhui Medical University from January 2007 to January 2014 were included in this study. Univariate and multivariate analyses were used to screen for prognostic risk factors. We constructed the nomogram based on Cox proportional hazard regression models. The construction of the new score models was analyzed by the receiver operator characteristic curve (ROC curve), which were compared with other clinical indexes.Results: Multivariate analysis showed that TNM stage, CA199, CEA, globulin, neutrophil-to-lymphocyte ratio (NLR), and lymphocyte-to-monocyte ratio (LMR) were independent prognostic factors. The new score system had a higher AUC value than other risk factors, and the C-index of the nomogram was highly consistent for evaluating survival of PDAC patients in the validation groups and training group, and the external population also verified the nomogram.Conclusions: For the patients with PDAC after radical surgery, we developed a precise model to predict the prognosis based on the serum markers and other clinical indicators. For surgeons and patients, this score system can be an effective help.

Abstract Background Adipose tissue is a widely used autologous soft tissue filler in plastic surgery, particularly for volumetric restoration in cases of soft tissue deficiency. However, effectively controlling the retention rate of transplanted fat remains a major challenge. Therefore, this study aims to explore strategies to enhance fat graft retention. We isolated fascia-derived stem cells (FDSCs) from human superficial fascia and compared their gene expression profiles with those of adipose-derived stem cells (ADSCs). Through bioinformatics analysis and functional experiments, we identified significant differences in the angiogenic potential of the two cell types. Based on sequencing results, we further investigated the roles of hypoxia-inducible factor-1α (HIF-1α) and heme oxygenase-1 (HMOX1). This study highlights the critical potential of FDSCs in improving fat graft retention and promoting angiogenesis, offering new strategies for enhancing graft survival and optimizing tissue regeneration therapies. Methods We isolated fascia-derived stem cells (FDSCs) from human superficial fascia and compared them with adipose-derived stem cells (ADSCs). RNA sequencing was performed to analyze gene expression profiles, followed by bioinformatics analysis to identify differences in angiogenic potential. Functional experiments were conducted to investigate the roles of HIF-1α and HMOX1 in angiogenesis. Results RNA sequencing revealed significant gene expression differences related to angiogenesis in FDSCs. The expression levels of HMOX1, HIF-1α, and VEGFa were significantly higher in FDSCs than in ADSCs, and HMOX1 positively regulated the expression of HIF-1α and VEGFa. In vitro experiments demonstrated that FDSCs promoted angiogenesis more effectively than ADSCs. In vivo co-transplantation experiments further confirmed that FDSCs improved fat graft retention and vascularization. Conclusions We demonstrated that FDSCs can more effectively promote vascularization both in vitro and in vivo, and significantly improve graft retention, indicating their broad potential for future applications in tissue repair and regeneration.

Abstract Fully π-conjugated polymers consisting of plane and rigid aromatic units present a fantastic optoelectronic property, a promising candidate for printed and flexible optoelectronic devices. However, obtaining high-performance conjugated polymers with an excellent intrinsically flexible and printable capacity is a great challenge due to their inherent coffee-ring effect and brittle properties. Here, we report an asymmetric substitution strategy to improve the printable and stretchable properties of deep-blue light-emitting conjugated polymers with a strong inter-aggregate capillary interaction for flexible printed polymer light-emitting diodes. The loose rod-shaped stacking of asymmetric conjugated polymers chain in the precursor printed ink makes it easier to improve the intrinsic stretchability of inkjet-printed films. More interestingly, the anisotropic shape rod-like aggregate of conjugated polymers chains also induced a strong capillary interaction and further suppressed the coffee-ring effect, which is more likely to allow for uniform deposition during printed processing and form uniform printed films.

BackgroundChyle leaks (CL) is a significant postoperative complication following lymph node dissection in cancer patients. Persistent CK is related to a series of adverse outcomes. Nutritional management is considered an effectively strategy that treat CL. However, the existing evidence on nutritional management for this patient cohort fails to provide actionable clinical guidance.AimThis study was aimed to establish an evidence-based framework for nutritional management, offering reliable basis for clinical nursing practice.MethodsUtilizing the “6S” mode, we conducted a systematic search of UpToDate, BMJ, Best Practice, Cochrane Library, Joanna Briggs Institute (JBI) Center for Evidence-Based Health Care Database, National Guideline Clearinghouse (NGC), Guidelines International Network (GIN), National Institute for Health and Care Excellence (NICE), Scottish Intercollegiate Guidelines Network (SIGN), Registered Nurses' Association of Ontario (RNAO), World Health Organization, Medlive, American Society for Parenteral and Enteral Nutrition (ASPEN), European Society for Clinical Nutrition and Metabolism (ESPEN), Web of Science, PubMed, Embase, CINAHL, China Biology Medicine (CBM), and China National Knowledge Infrastructure (CNKI) for all evidence on the nutritional management of postoperative coeliac leakage in cancer patients. This search included guidelines, evidence summaries, expert consensus, clinical decision-making, recommended practices, systematic evaluations or Meta-analyses, randomized controlled trials (RCTs), and class experiments. The search timeframe was from the library's establishment to June 2024. Quality assessment of the literature was completed independently by two researchers with professional evidence-based training and expert advice, and evidence was extracted and summarized for those that met the quality criteria.ResultsA total of 13 articles were included in the analysis, comprising two expert consensus, one guideline, one class of experimental studies, seven systematic evaluations, and two clinical decisions. We summarized 22 pieces of evidence across five categories: nutritional screening, assessment, and monitoring, timing of nutritional therapy, methods and approaches to nutritional therapy, nutrient requirements, and dietary modification strategies.ConclusionThis study presents key evidence for nutritional management in cancer patients with CL post-surgery, emphasizing nutritional screening, assessment, timing and methods of therapy, and dietary adjustment strategies. It emphasized the necessity of thorough screening tools for the assessment of nutritional condition, and the benefits of early enteral feeding. A multidisciplinary team approach is vital for conducting personalized dietary, while sustained nutritional support, dietary fat restrictions, and medium-chain triglycerides enhance nutrient absorption. Consistent monitoring of chylous fluid output and timely dietary adjustments are crucial for improving patient outcomes and recovery.Systematic review registrationhttp://ebn.nursing.fudan.edu.cn/registerResources, identifier ES20244732.

Ginsenosides has been extensively used in clinical settings to treat various inflammatory diseases. At present, the anti-inflammatory effect of ginsenosides is mainly focused on monomeric ginsenosides, while the total saponins of ginseng and their synergistic effect with probiotic fermentation products are rarely studied. This study aimed to investigate the mitigative effects of fermented ginsenosides with Pediococcus acidilactici on Enterotoxigenic Escherichia coli diarrhea in mice. P. acidilactici XM-06 and ginsenoside fermentation products demonstrated significant pre-protection against ETEC-induced diarrhea by mitigating inflammation, inhibited the ERK and upregulated the Z0–1, 0ccludin and Claudin-1 levels, and reducing oxidative stress. These products not only repaired intestinal mucosal damage caused by ETEC-induced diarrhea in mice but also positively influenced gut microbiota dysbiosis by increasing the abundance of Lactobacillus and Bacteroides while decreasing the abundance of Enterobacter, potentially providing a new natural product for the prevention of ETEC-associated diarrheal diseases in humans.

BACKGROUND: The effect of neoadjuvant chemotherapy (NAC) on Gastric carcinoma (GC) has been extensively studied, while its survival and surgical benefits remain controversial. This study aims to perform a meta-analysis of high-quality randomized controlled trials (RCTs), comparing efficacy, safety and other outcomes of NAC followed by surgery with surgery alone (SA) for GC. METHODS: We systematically searched databases of MEDLINE, EMBASE, The Cochrane Library and Springer for RCTs comparing NAC with SA when treating GC. Reference lists of relevant articles and reviews, conference proceedings and ongoing trial databases were also searched. Primary outcomes were 3-year and 5-year survival rates, survival time, and total and perioperative mortalities. Secondary outcomes included down-staging effects, R0 resection rate, and postoperative complications. Meta-analysis was conducted where possible comparing items using relative risks (RRs) and weighted mean differences (WMDs) according to type of data. NAC-related objective response, safety and toxicity were also specifically analyzed. RESULTS: A total of 9 RCTs comparing NAC (n = 511) with SA (n = 545) published from 1995 to 2010 were identified. SA tended to be accompanied with higher overall mortality rate than NAC (46.03% vs 40.61%, RR: 0.83, 95% CI: 0.65-1.06, P = 0.14). Significantly, higher incidence of cases without regional lymph node metastasis observed upon resection were achieved among patients receiving NAC than those undergoing SA (25.68% vs 16.95%, RR: 1.92, 95% CI: 1.20-3.06, P = 0.006). All other parameters were comparable. Of the evaluable patients, 43.0% demonstrated either complete or partial response. The comprehensive NAC-related side-effect rate was 18.2% among patients available for safety assessment. CONCLUSIONS: NAC contributes to lowering nodal stages, and potentially reduces overall mortality. Response rate may be an important influential factor impacting advantages, with chemotherapy-related adverse effects as a drawback. This level 1a evidence doesn't support NAC to outweigh SA in terms of survival and surgical benefits when dealing with GC.

Twenty-two coumarins and twenty-six flavonoids were quantitated in fingered citron in different growth periods. Limettin was the top coumarin, and diosmin was the highest flavonoid, followed by hesperidin. Antioxidant evaluation by DPPH, ABTS, and FRAP indicated extracts of fingered citron in three growth periods all showed good antioxidant activity, which was positively correlated with the concentration of extracts. The oxidative stress model of RAW264.7 cells indicated extracts from fingered citron effectively reduced the contents of NO, MDA, and ROS in cells and increased the activity of SOD, thereby alleviating cell damage. The antioxidant capacity of fingered citron in November was the highest, followed by July and September. And there was a significantly positive correlation between the total flavonoid content and the antioxidant capacity. Diosmin, hesperidin, and neohesperidin were the main contributors to antioxidation. This study has significance for utilization of fingered citron germplasm resources and development of related functional products.

The application of Trajectory-Based Operation (TBO) and Free-Route Airspace (FRA) can relieve air traffic congestion and reduce flight delays. However, this new operational framework has higher requirements for the reliability and efficiency of the trajectory, which will be significantly influenced if the analysis of wind uncertainty during trajectory planning is insufficient. In the literature, trajectory planning models considering wind uncertainty are developed based on the time-invariant condition (i.e., three-dimensional), which may potentially lead to a significant discrepancy between the predicted flight time and the real flight time. To address this problem, this study proposes a trajectory planning model considering time-variant wind uncertainty (i.e., four-dimensional). This study aims to optimize a reliable and efficient trajectory by minimizing the Mean-Excess Flight Time (MEFT). This model formulates wind as a discrete variable, forming the foundation of the proposed time-variant predicted method that can calculate the segment flight time accurately. To avoid the homogeneous assumption of distributions, we specifically apply the first four moments (i.e., expectation, variance, skewness, and kurtosis) to describe the stochasticity of the distributions, rather than using the probability distribution function. We apply a two-stage algorithm to solve this problem and demonstrate its convergence in the time-variant network. The simulation results show that the optimal trajectory has 99.2% reliability and reduces flight time by approximately 9.2% compared to the current structured airspace trajectory. In addition, the solution time is only 2.3 min, which can satisfy the requirement of trajectory planning.

During the use of optical gun scopes, slight movements between the human eye and the instrument can cause the pupil to offset from the optical axis, resulting in a dynamic distortion effect. This affects the accuracy and stability of aiming. Based on the mechanism, this study established parameters of the centroid’s deviation of image spots for marginal field points under pupil decentering and centering conditions and their differences to quantitatively evaluate the distortion. These evaluation parameters were obtained by performing a double integral calculation of the ray aberration distribution function over the entire designed exit pupil. Based on this evaluation method, three optical design strategies for reducing the distortion were proposed: optimizing ray aberrations, optimizing centroid shift of image spots, and utilizing vignetting effects. An optimization process was established by combining increasing vignetting and suppressing centroid shift. For a gun scope with significant distortion, the distortion effect was significantly weakened by increasing the vignetting factor and optimizing the centroid shift of image spots. This proved the effectiveness of the proposed analysis, evaluation, and optimization design methods.

Today due to the development of technologies a new economy, network economy is formed. The network business is an economic activity carried out through digital networks. The introduction of the network economy into production at the present stage is conditioned by a special economic category or form of industrial relations in cooperation with the development of productive forces and economic phenomena. In the context of digitalization, contradictory requirements are beginning to be placed on production. In the first case, it is about low costs and high variability, in the other case, the life cycle of a product is beginning to shorten rapidly. All of these problems can be solved at different stages of digital transformation. Continued innovation is needed today, as progress in the existence and effectiveness of some organizations becomes almost impossible without technological innovation. Flexibility of reaction of people to changes and development of new methods of activity are the leading conditions of competitiveness of modern enterprise. The object of this study is new opportunities, various aspects of digitalization of production, optimization of enterprise resources. The key aspect is to increase the productivity of the enterprise by reducing the time of the development of new products marketed and delivered to the consumer. As a result, the reduction contributes to overall efficiency. The authors substantiate that digitalization of production is the consolidation of all business processes at the enterprise using computer and information technologies. The basis of the introduction of the latest technologies is the desire of any company to comprehensively increase the efficiency of production, demand among customers and competitiveness. Keywords: economy, production, process, technology, digitalization, labor productivity, efficiency.

Abstract Objectives To evaluate the manufacturability, efficacy and safety of allogeneic CD19 chimeric antigen receptor double‐negative T cells (CD19‐CAR‐DNTs) as an off‐the‐shelf therapeutic cell product. Methods A membrane proteome array was used to assess the off‐target binding of CD19‐CAR. DNTs derived from healthy donors were transduced with lentiviral vectors encoding the CD19‐CAR. The manufacture of the CD19‐CAR‐DNTs was under GMP conditions, and their surface molecule expression patterns were characterised using flow cytometry. We investigated the off‐the‐shelf potential of CD19‐CAR‐DNTs by evaluating the cryopreserved CD19‐CAR‐DNTs in terms of cell viability as well as their cytotoxicity against various CD19+ target cell lines and primary patient blasts in vitro. We evaluated the persistence and safety of the cryopreserved CD19‐CAR‐DNTs in xenograft models in vivo. Results GMP‐grade CD19‐CAR‐DNTs were manufactured and cryopreserved for use in advance. The cryopreserved CD19‐CAR‐DNTs maintain their viability and antitumor activity against various CD19+ target cell lines and primary patient blasts. These cells significantly prolonged the survival in Raji‐Luc‐xenografted NOG mice. Multiple infusions of the cells can further augment their efficacy. Remarkably, following a single infusion in mice, CD19‐CAR‐DNTs rapidly got distributed among well‐perfused organs initially, and progressively spread to most tissues, peaking at Day 43. In toxicity studies, CD19‐CAR‐DNTs significantly reduced tumor burden and ameliorated tissue damage in tumor‐bearing NOG mice. Critically, no immunotoxicity or graft versus host disease was observed in non‐tumor‐bearing NOG mice. Conclusions The allogeneic CD19‐CAR‐DNTs fulfil the requirements of an off‐the‐shelf therapeutic cell product, offering a promising new approach to the treatment of haematological malignancies.

Introduction: This study explores the relationships among gratitude, perceived social support, prosocial tendencies, and psychological well-being (PWB) in Chinese university students. Despite growing interest in these constructs, the mechanisms through which gratitude and social support influence PWB remain underexplored, particularly in collectivist cultural contexts where social harmony and interdependence are prioritized. Methods: Data were collected from 703 Chinese university students using validated instruments measuring gratitude, perceived social support, prosocial tendencies, and psychological well-being. Structural equation modeling (SEM) was employed to test the direct and indirect effects of gratitude and social support on PWB, with prosocial tendencies modeled as a mediating higher-order factor. Multi-group SEM analysis was conducted to examine gender invariance. Results: Gratitude and perceived social support significantly predicted PWB, both directly and indirectly through prosocial tendencies. Gratitude had a strong positive effect on prosocial tendencies (β = 0.412, p < 0.001), which, in turn, significantly contributed to PWB (β = 0.465, p < 0.001). Similarly, perceived social support positively influenced prosocial tendencies (β = 0.375, p < 0.001) and PWB (β = 0.253, p < 0.05). Mediation analysis confirmed that prosocial tendencies partially mediated these relationships. Multi-group SEM analysis revealed structural invariance across gender. Discussion: The findings underscore the cultural relevance of gratitude and social support within Chinese society, emphasizing the role of collectivist values in fostering PWB. Practical implications include implementing gratitude-focused interventions and enhancing peer support systems within university mental health programs to promote resilience and well-being among students. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate the effects of alfalfa polysaccharides on the lactation performance and immune function of dairy cows. Methods: A total of 84 healthy Holstein cows were selected and randomly divided into 7 groups, including the control Group A0, the alfalfa polysaccharide groups (AP1, AP2, AP3) and the alfalfa extract groups (AE1, AE2, AE3). Each group had three replicates and each replicate had four cows. The daily rations of the dairy cows in the AP group and the AE group were supplemented with alfalfa polysaccharide powder and alfalfa extract at concentrations of 1, 2 and 3 kg/t, those in the A0 group served as a control. Result: (1) the milk production of dairy cows in the AE groups was extremely significantly greater (p<0.01) than that in A0 group and AP groups. The milk protein content of cows in the AP2 and AE2 groups was significantly greater (P<0.05) than that in the A0 group (2) The interleukin-2 (IL-2) levels in the serum of cows in the AP2, AP3, AE2 and AE3 groups were greater than those in the A0 and AP1 groups and the IgM antibody levels in the AP group and the AE group were extremely significantly greater than those in the A0 and AP1 groups (P<0.01). The IgA antibody level in the serum of dairy cows in the AP2, AP3, AE2 and AE3 groups was significantly (P<0.01) greater than that in the A0, AP1 and AE1 groups. In summary, the alfalfa extract improved both the lactation performance and immunity of dairy cows, indicating comprehensive effects. Alfalfa polysaccharides at a concentration of 2 kg/t improved the immunity of dairy cows. [ABSTRACT FROM AUTHOR]

Background: The CTNND2 gene which encodes a δ-catenin protein (CTNND2) is associated with multiple severe neurological disorders. However, the specific role of CTNND2 in spatial cognition and related mechanisms remains obscure. Methods: In this study, we generated a new line of Ctnnd2-Knock out (KO) mice with its exon2 deleted, and then characterized their behavioral phenotypes and explore the Biological mechanism. Results: Ctnnd2-KO mice were with typical autism-like behaviors as evidenced by reduced social interaction in three-chamber sociability test, more frequent stereotypic behaviors (self-grooming), and deficits in spatial learning and memory tested by the Morris water maze. Furthermore, the expression of Rictor protein, a core component of the mTORC2 complex, was significantly decreased in the hippocampus of mutant mice. ShRNA-induced knockdown of Rictor protein in the hippocampus of both Ctnnd2-KO mice and wild-type mice exacerbated spatial learning and memory deficits but did not affect their autism-like behaviors. Mechanistically, the hippocampal CA1 neurons of Ctnnd2-KO mice showed decreased actin polymerization, postsynaptic spine density. Down-regulation of Rictor resulted in altered expression of post-synaptic proteins such as GluR1 and ELKS, but not presynaptic protein Synapsin1, implying abnormal synaptic changes in KO mice. Conclusion: The CTNND2 gene is involved in spatial learning and memory via Rictor-mediated actin polymerization and synaptic plasticity. Our study provides a novel insight into the role and mechanisms of the Ctnnd2 gene in cognition at the molecular and synaptic levels. Highlights: 1. Ctnnd2−/− mice exhibited autism-like behaviors and impaired spatial learning and memory. 2. Rictor was involved in the regulation of Ctnnd2-associated spatial cognition but not autism-like behaviors. 3. Rictor played a crucial role in spatial learning and memory by modulating postsynaptic changes in hippocampal neurons of Ctnnd2-⁣/- mice.

Abstract Background Nitrogen (N) is an important nutrient for plant growth, development, and agricultural production. Nitrogen stress could induce epigenetic changes in plants. In our research, overexpression of the OsNAR2.1 line was used as a testing target in rice plants with high nitrogen-use efficiency to study the changes of rice methylation and growth in respond of the endogenous and external nitrogen stress. Results Our results showed that external N deficiency could decrease seed N content and plant growth of the overexpression line. During the filial growth, we found that the low parent seed nitrogen (LPSN) in the overexpression line could lead to a decrease in the filial seed nitrogen content, total plant nitrogen content, yield, and OsNAR2.1 expression (28, 35, 23, and 55%, respectively) compared with high parent seed nitrogen (HPSN) in high nitrogen external supply. However, such decreases were not observed in wild type. Furthermore, methylation sequencing results showed that LPSN caused massive gene methylation changes, which enriched in over 20 GO pathways in the filial overexpression line, and the expression of OsNAR2.1 in LPSN filial overexpression plants was significantly reduced compared to HPSN filial plants in high external N, which was not shown in wild type. Conclusions We suggest that the parent seed nitrogen content decreased induced DNA methylation changes at the epigenetic level and significantly decreased the expression of OsNAR2.1, resulting in a heritable phenotype of N deficiency over two generations of the overexpression line.

Small‐cell lung cancer (SCLC) occurs infrequently in never/former light smokers. We sought to study this rare clinical subset through next‐generation sequencing (NGS) and by characterizing a representative patient‐derived model. We performed targeted NGS, as well as comprehensive pathological evaluation, in 11 never/former light smokers with clinically diagnosed SCLC. We established a patient‐derived model from one such patient (DFCI168) harboring an NRASQ61K mutation and characterized the sensitivity of this model to MEK and TORC1/2 inhibitors. Despite the clinical diagnosis of SCLC, the majority (8/11) of cases were either of nonpulmonary origin or of mixed histology and included atypical carcinoid (n = 1), mixed non‐small‐cell lung carcinoma and SCLC (n = 4), unspecified poorly differentiated carcinoma (n = 1), or small‐cell carcinoma from different origins (n = 2). RB1 and TP53 mutations were found in four and five cases, respectively. Predicted driver mutations were detected in EGFR (n = 2), NRAS (n = 1), KRAS (n = 1), BRCA1 (n = 1), and ATM (n = 1), and one case harbored a TMPRSS2‐ERG fusion. DFCI168 (NRASQ61K) exhibited marked sensitivity to MEK inhibitors in vitro and in vivo. The combination of MEK and mTORC1/2 inhibitors synergized to prevent compensatory mTOR activation, resulting in prolonged growth inhibition in this model and in three other NRAS mutant lung cancer cell lines. SCLC in never/former light smokers is rare and is potentially a distinct disease entity comprised of oncogenic driver mutation‐harboring carcinomas morphologically and/or clinically mimicking SCLC. Comprehensive pathologic review integrated with genomic profiling is critical in refining the diagnosis and in identifying potential therapeutic options.

AIM:To observe the effect of different time of wearing overnight orthokeratology lens(OOK lens)on the meibomian gland and detection rate of demodex.METHODS:Case-control study. Totally 47(91 eyes)patients who wearing keratoscopy were enrolled from June 2019 to December 2019 in Hanyang Aier Eye Hospital. According to the wearing time, they were divided into short-term group(wearing time RESULTS: The three groups of NI-BUT were 12.68±4.59s, 12.37±4.97s, 10.45±6.04s,(P>0.05). BRS respectively were 0.99±0.41, 0.90±0.37, 0.84±0.35,(P>0.05). Meibomian gland score for all three groups: 1(0, 1)(P>0.05). In the three groups, the detection rate and quantity of demodex were 42%, 1(1, 2); 39%, 2(1, 2); 33%, 1(1, 2),(P>0.05). Among the patients with corneal staining, 5 were mite positive and 11 were mite negative(P>0.05). Meibomian gland score: 4 eyes were 0 grade, 12 eyes were 1 grade above(P>0.05). Short-term group 6 eyes, long-term group 10 eyes(P>0.05). CONCLUSION:There was no significant effect on meibomian gland, the detection rate and quantity of demodex in patients wearing OOK lens. Whereas no significant relationship between meibomian gland score/ demodex detection rate and corneal staining.

In this study, a switchable coding metasurface was demonstrated in the terahertz (THz) frequency range to realize dynamic beam steering based on a Dirac semimXetal. The relative phase delay of the proposed metamaterials unit cell can be actively controlled by changing the Fermi level (EF) of the Dirac semimetal film (DSF). For the 1-bit coding metasurface, the coding units with ‘0′ and ‘1′ states can be switched on/off in the frequency range of 1.46–2 THz by changing the EF value of the DSF. The beam numbers and propagation direction of the reflected waves in such 1-bit coding metasurfaces can be engineered at will. Moreover, a dynamically controlled 2-bit coding metasurface was constructed based on DSF microstructures to realize more sophisticated beam manipulation. When EF was set to 0.3 eV, the relative phase delay of the four-unit structure at 1.0 THz was increased from 0° to 360° with an interval of 90°. When EF decreased to 0.02 eV, the relative phase delay of the four-unit structure was reduced accordingly, and the phase coverage decreased to only 30°. Based on the above results, switching between abnormal/specular reflection and on/off vortex generation were realized. The proposed coding metasurfaces are promising for use in THz communication and sensing applications.

ObjectiveTo investigate the feasibility of intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) in evaluating early effects of anti-angiogenic therapy in the C6 glioma rat model.MethodsTwenty-six rats of the C6 glioma model were randomly divided into a treatment group (received bevacizumab) and a control group (physiological saline). IVIM-DWI was performed on days 0, 1, 3, 5, and 7 after anti-angiogenic therapy and tumor growth and IVIM-DWI parameters were dynamically observed. Hematoxylin and eosin, CD34 microvessel density (MVD), proliferation of cell nuclear antigen (PCNA), and Hif-α staining were performed on day 7. One-way ANOVA was used to compare intra-group differences and an independent-samples t-test was used to compare inter-group differences of MRI parameters. Correlations between IVIM-DWI parameters, tumor size, and pathological results were analyzed.ResultsThe relative change in tumor volume (ΔVolume) in the two groups differed significantly on days 5 and 7 (p = 0.038 and p < 0.001). The perfusion-related parameters D*- and f-values decreased in the treatment group and demonstrated significant differences compared with the control group on days 3, 5, and 7 (p = 0.033, p < 0.001, and p < 0.001, respectively). The diffusion-related parameters ADC and D-values increased in the treatment group and were found to be significantly differently different from the control group on days 5 and 7 (both p < 0.001). The initial D-value showed a negative correlation with ΔVolume (γ = −0.744, p < 0.001), whereas the initial D*-value and relative change of D-value had a positive correlation with ΔVolume (γ = 0.718, p < 0.001 and γ = 0.800, p < 0.001, respectively). MVD was strongly positively correlated with D*-value (r = 0.886, p = 0.019), PCNA was negatively correlated with ADC- and D-values (r = −0.848, p = 0.033; and r = −0.928 p = 0.008, respectively), and Hif-1α was strongly negatively correlated with D*-value (r = −0.879, p = 0.010).ConclusionIVIM-DWI was sensitive and accurate in predicting and monitoring the effects of early anti-angiogenesis therapy in a C6 glioma rat model.

Polymyxin B (PMB) exert bactericidal effects on the cell wall of Gram-negative bacteria, leading to changes in the permeability of the cytoplasmic membrane and resulting in cell death, which is sensitive to the multi-resistant Gram-negative bacteria. However, the severe toxicity and adverse side effects largely hamper the clinical application of PMB. Although the molecular pathology of PMB neurotoxicity has been adequately studied at the cellular and molecular level. However, the impact of PMB on the physiological states of central nervous system in vivo may be quite different from that in vitro, which need to be further studied. Therefore, in the current study, the biocompatible ultra-uniform Fe3O4 nanoparticles were employed for noninvasively in vivo visualizing the potential impairment of PMB to the central nervous system. Systematic studies clearly reveal that the prepared Fe3O4 nanoparticles can serve as an appropriate magnetic resonance contrast agent with high transverse relaxivity and outstanding biosafety, which thus enables the following in vivo susceptibility-weighted imaging (SWI) studies on the PMB-treated mice models. As a result, it is first found that the blood-brain barrier (BBB) of mice may be impaired by successive PMB administration, displaying by the discrete punctate SWI signals distributed asymmetrically across brain regions in brain parenchyma. This result may pave a noninvasive approach for in-depth studies of PMB medication strategy, monitoring the BBB changes during PMB treatment, and even assessing the risk after PMB successive medication in multidrug-resistant Gram-negative bacterial infected patients from the perspective of medical imaging.

Syphilis, caused by the spirochete Treponema pallidum subspecies pallidum, continues to be a major public health problem worldwide. Recent increases in the number of syphilis cases, in addition to the lack of an efficient vaccine against T. pallidum for humans, highlights an urgent need for the design and development of an efficacious syphilis vaccine. Here, we assess the vaccine potential of the adhesion protein Tp0136 and the outer membrane protein Tp0663. Rabbits were subcutaneously immunized with recombinant proteins Tp0136, Tp0663, or control PBS. Immunization with Tp0136 or Tp0663 generated a strong humoral immune response with high titers of IgG, as assessed by ELISA. Moreover, animals immunized with Tp0136 or Tp0663 exhibited attenuated lesion development, increased cellular infiltration at the lesion sites, and inhibition of treponemal dissemination to distant organs compared to the unimmunized animals. These findings indicate that Tp0136 and Tp0663 are promising syphilis vaccine candidates. Furthermore, these results provide novel and important information for not only understanding the pathogenic mechanisms of spirochetes, but also the development of spirochete-specific subunit vaccines.

Cadherins play an important role in tissue homeostasis, as they are responsible for cell-cell adhesion during embryogenesis, tissue morphogenesis, and differentiation. In this study, we identified Cadherin-12 (CDH12), which encodes a type II classical cadherin, as a gene that promotes neurite outgrowth in an in vitro model of neurons with differentiated intrinsic growth ability. First, the effects of CDH12 on neurons were evaluated via RNA interference, and the results indicated that the knockdown of CDH12 expression restrained the axon extension of E18 neurons. The transcriptome profile of neurons with or without siCDH12 treatment revealed a set of pathways positively correlated with the effect of CDH12 on neurite outgrowth. We further revealed that CDH12 affected Rac1/Cdc42 phosphorylation in a PKA-dependent manner after testing using H-89 and 8-Bromo-cAMP sodium salt. Moreover, we investigated the expression of CDH12 in the brain, spinal cord, and dorsal root ganglia (DRG) during development using immunofluorescence staining. After that, we explored the effects of CDH12 on neurite outgrowth in vivo. A zebrafish model of CDH12 knockdown was established using the NgAgo-gDNA system, and the vital role of CDH12 in peripheral neurogenesis was determined. In summary, our study is the first to report the effect of CDH12 on axonal extension in vitro and in vivo, and we provide a preliminary explanation for this mechanism.

Abstract Let T > 1 $T > 1$ be an integer, and let T = { 1 , 2 , … , T } $\mathbb{T}=\{1, 2,\ldots ,T\}$ . We show the existence of positive solutions of the Dirichlet boundary value problem with second-order difference operator { − △ 2 u ( j − 1 ) = λ f ( j , u ( j ) ) , j ∈ T , u ( 0 ) = u ( T + 1 ) = 0 , $$ \textstyle\begin{cases} -\triangle ^{2} u(j-1)=\lambda f(j, u(j)), \quad j\in \mathbb{T},\\ u(0)=u(T + 1)=0, \end{cases} $$ where λ > 0 $\lambda >0$ is a parameter, and f : T × R + → R $f:\mathbb{T}\times \mathbb{R} ^{+}\to \mathbb{R}$ is a continuous function satisfying f ( j , 0 ) < 0 $f(j, 0)

With the help of machine learning (ML) techniques, the possible errors made by the pathologists and physicians, such as those caused by inexperience, fatigue, stress and so on can be avoided, and the medical data can be examined in a shorter time and in a more detailed manner. However, while the conventional ML techniques, such as classification, achieved excellent performance in classification accuracy when applied in medical diagnoses, they have a fatal shortcoming of poor performance since the imbalanced dataset, especially for the detection of the minority category. To tackle the shortcomings of conventional classification approaches, this study proposes a novel ensemble learning paradigm for medical diagnosis with imbalanced data, which consists of three phases: data pre-processing, training base classifier and final ensemble. In the first data pre-processing phase, we introduce the extension of Synthetic Minority Oversampling Technique (SMOTE) by integrating it with cross-validated committees filter (CVCF) technique, which can not only synthesize the minority sample and thereby balance the input instances, but also filter the noisy examples so as to perform well in the process of classification. In the classification phase, we introduce ensemble support vector machine (ESVM) classification technique, which were constructed by multiple diversity structures of SVM classifiers and thus has the advantages of strong generalization performance and classification precision. Additionally, in the last phase of the final ensemble strategy, we introduce the weighted majority voting strategy and introduce simulated annealing genetic algorithm (SAGA) to optimize the weight vector and thereby enhance the overall classification performance. The efficiency of our proposed ensemble learning method was tested on nine imbalanced medical datasets and the experimental results clearly indicate that the proposed ensemble learning paradigm outperforms other state-of-the-art classification models. Promisingly, our proposed ensemble learning paradigm can effectively facilitate medical decision making for physicians.

Stenotrophomonas maltophilia (S. maltophilia) is an emerging opportunistic pathogen that exhibits resistant to a majority of commonly used antibiotics. Phages have the potential to serve as an alternative treatment for S. maltophilia infections. In this study, a lytic phage, A1432, infecting S. maltophilia YCR3A-1, was isolated and characterized from a karst cave. Transmission electron microscopy revealed that phage A1432 possesses an icosahedral head and a shorter tail. Phage A1432 demonstrated a narrow host range, with an optimal multiplicity of infection of 0.1. The one-step growth curve indicated a latent time of 10  min, a lysis period of 90  min, a burst size of 43.2 plaque-forming units per cell. In vitro bacteriolytic activity test showed that phage A1432 was capable to inhibit the growth of S. maltophilia YCR3A-1 in an MOI-dependent manner after 2  h of co-culture. BLASTn analysis showed that phage A1432 genome shares the highest similarity (81.46%) with Xanthomonas phage Xoo-sp2 in the NCBI database, while the query coverage was only 37%. The phage contains double-stranded DNA with a genome length of 61,660  bp and a GC content of 61.92%. It is predicted to have 79 open reading frames and one tRNA, with no virulence or antibiotic resistance genes. Phylogenetic analysis using terminase large subunit and DNA polymerase indicated that phage A1432 clustered with members of the Bradleyvirinae subfamily but diverged into a distinct branch. Further phylogenetic comparison analysis using Average Nucleotide Identity, proteomic phylogenetic analysis, genomic network analysis confirmed that phage A1432 belongs to a novel genus within the Bradleyvirinae subfamily, Mesyanzhinovviridae family. Additionally, phylogenetic analysis of the so far isolated S. maltophilia phages revealed significant genetic diversity among these phages. The results of this research will contribute valuable information for further studies on their morphological and genetic diversity, will aid in elucidating the evolutionary mechanisms that give rise to them. [ABSTRACT FROM AUTHOR]

Dihydrotanshinone I (DHT) is a natural component in Salvia miltiorrhiza and has been widely researched for its multiple bioactivities. However, poor solubility and biocompatibility of DHT limit its desirable application for clinical purposes. Herein, DHT was encapsulated with bovine serum albumin (BSA) to enhance bioavailability. Compared to free DHT, DHT–BSA NPs (nanoparticles) showed an improved solubility in normal saline and increased protection against hydrogen peroxide–induced oxidative damage in PC12 cells. In addition, DHT–BSA NPs administered by intravenous injection displayed a significant efficacy in the middle cerebral artery occlusion/reperfusion models, without any impact on the cerebral blood flow. In summary, DHT–BSA NPs show an enhanced bioavailability compared with free DHT and a successful penetration into the central nervous system for stroke therapy, demonstrating their application potential in cardio–cerebrovascular diseases.

BackgroundAutophagy related protein 5 (ATG5) is an important autophagosome formation related protein, and its involvement in the biological process of autophagy has been shown to correlate with tumor metabolic patterns and the formation of tumor heterogeneity. However, the role of ATG5 in tumor metabolism and tumor immunity remains unclear.MethodIn order to explore this problem, this study was designed to reveal the role of ATG5 in tumor metabolism and tumor immunity through pan-cancer analysis of multi-database. GTEx database, CCLE database, and TCGA database were used to describe the expression, prognosis, immune microenvironment, immune new antigen, immune checkpoint, TMB, and microsatellite instability of ATG5 in 33 types of tumors. A series of bioinformatics tools and methods were used for quantitative analysis and panoramic description, such as to Estimate, Scanneo and GSEA.ResultThe differential analysis results of multiple databases showed that ATG5 was ubiquitously highly expressed in pan-cancer, especially in solid tumors. Survival analysis revealed that ATG5 was universally associated with the prognosis of pan-cancer, and high ATG5 expression was significantly associated with poor patient prognosis in most cases. Further, the expression level of ATG5 was confirmed to be associated with tumor immune infiltration and tumor microenvironment, especially in BRCA, KIRC, and LIHC. In addition to this, ATG5 expression was confirmed to correlate with these clinically significant phenotypes, in conjunction with immune neoantigens and immune checkpoint gene expression profiles in pan-cancer. In addition to TMB and microsatellite instability in pan-cancer, we confirmed that ATG5 expression affects the expression of DNA repair genes and methyltransferases in pan-cancer, and found through gene set enrichment analysis that ATG5 is involved in the regulation of numerous signaling pathways involved in cancer metabolism and cancer immunity.ConclusionsATG5 participated in the formation of autophagosomal membrane important molecule LC3-II outside, and played an important role in tumor metabolism and tumor immunity. The comprehensive pan-cancer analysis not only revealed the potential of ATG5 in tumor-targeted therapy but also suggested ATG5 as a promising tumor predictive biomarker in most solid tumors.

Human bocavirus 1 (HBoV1), a common pediatric respiratory pathogen, can persist in airway secretions for months hampering diagnosis. It also persists in tonsils, providing potential reservoirs for airway shedding, with the exact location, host cell types, and virus activity unknown.

The spirochetal pathogen Treponema pallidum causes 5 million new cases of venereal syphilis worldwide each year. One major obstacle to syphilis prevention and treatment is the lack of suitable experimental animal models to study its pathogenesis. Accordingly, in this study, we further evaluated the responses of mice to Treponema pallidum. Quantitative polymerase chain reaction showed that Treponema pallidum could colonize the heart, liver, spleen, kidneys, and testicles of C57BL/6 mice, and the organism may be able to rapidly penetrate the blood-brain barrier in mice by 24 h after infection. In subsequent rabbit infectivity tests, we observed evident signs of the microorganism in the mouse lymph node suspension. After infection, bacterial loads were higher in the tissues than in the blood of C57BL/6 mice. Moreover, a significant Th1 immune response was recorded by cytokine assays. Flow cytometric analysis suggested an obvious increase in the proportion of CD3+ T and CD4+ T cells in the spleen cells in the infected mice. Thus, improving our understanding of the response of C57BL/6 mice for Treponema pallidum will help to comprehensive elucidate the pathogenic mechanisms of this bacterium and lay the foundation for the development of a new research model of Treponema pallidum.

Background: Renal tubulointerstitial fibrosis is the key pathological feature in chronic kidney diseases (CKDs) with no satisfactory therapies in clinic. Cilomilast is a second-generation, selective phosphodiesterase-4 inhibitor, but its role in renal tubulointerstitial fibrosis in CKD remains unclear.Material and Methods: Cilomilast was applied to the mice with unilateral ureteric obstruction (UUO) and renal fibroblast cells (NRK-49F) stimulated by TGF-β1. Renal tubulointerstitial fibrosis and inflammation after UUO or TGF-β1 stimulation were examined by histology, Western blotting, real-time PCR and immunohistochemistry. KIM-1 and NGAL were detected to evaluate tubular injury in UUO mice.Results:In vivo, immunohistochemistry and western blot data demonstrated that cilomilast treatment inhibited extracellular matrix deposition, profibrotic gene expression, and the inflammatory response. Furthermore, cilomilast prevented tubular injury in UUO mice, as manifested by reduced expression of KIM-1 and NGAL in the kidney. In vitro, cilomilast attenuated the activation of fibroblast cells stimulated by TGF-β1, as shown by the reduced expression of fibronectin, α-SMA, collagen I, and collagen III. Cilomilast also inhibited the activation of TGF-β1-Smad2/3 signaling in TGF-β1-treated fibroblast cells.Conclusion: The findings of this study suggest that cilomilast is protective against renal tubulointerstitial fibrosis in CKD, possibly through the inhibition of TGF-β1-Smad2/3 signaling, indicating the translational potential of this drug in treating CKD.

Plant leaf respiration is one of the critical components of the carbon cycle in terrestrial ecosystems. To predict changes of carbon emissions from leaves to the atmosphere under a warming climate, it is, therefore, important to understand the thermodynamics of the temperature response of leaf respiration. In this study, we measured the short-term temperature response of leaf respiration from five different urban tree species in a subtropical region of southern China. We applied two models, including an empirical model (the Kavanau model) and a mechanistic model (Macromolecular Rate Theory, MMRT), to investigate the thermodynamic properties in different plant species. Both models are equivalent in fitting measurements of the temperature response of leaf respiration with no significant difference (p = 0.67) in model efficiency, while MMRT provides an easy way to determine the thermodynamic properties, i.e., enthalpy, entropy, and Gibbs free energy of activation, for plant respiration. We found a conserved temperature response in the five studied plant species, showing no difference in thermodynamic properties and the relative temperature sensitivity for different species at low temperatures (

Purpose: Decreased serum ferritin level was recently found in schizophrenia. Whether the brain iron concentration in schizophrenia exists abnormality is of research significance. Quantitative susceptibility mapping (QSM) was used in this study to assess brain iron changes in the grey matter nuclei of patients with first-episode schizophrenia. Methods: The local ethics committee approved the study, and all subjects gave written informed consent. Thirty patients with first-episode schizophrenia and 30 age and gender-matched healthy controls were included in this study. QSM and effective transverse relaxation rate (R2*) maps were reconstructed from a three-dimensional multi-echo gradient-echo sequence. The inter-group differences of regional QSM values, R2* values and volumes were calculated in the grey matter nuclei, including bilateral caudate nucleus, putamen, globus pallidus, substantia nigra, red nucleus, and thalamus. The diagnostic performance of QSM and R2* was evaluated using receiver operating characteristic curve. The correlations between regional iron variations and clinical PANSS (Positive and Negative Syndrome Scale) scores were assessed using partial correlation analysis. Results: Compared to healthy controls, patients with first-episode schizophrenia had significantly decreased QSM values (less paramagnetic) in the bilateral substantia nigra, left red nucleus and left thalamus (p 0.05). Conclusion: This study reveals decreased iron concentration in grey matter nuclei of patients with first-episode schizophrenia. QSM provides superior sensitivity over R2* in the evaluation of schizophrenia-related brain iron changes. It demonstrated that QSM may be a potential biomarker for further understanding the pathophysiological mechanism of first-episode schizophrenia.

Background Cardiac remodeling predisposes individuals to heart failure if the burden is not solved, and heart failure is a growing cause of morbidity and mortality worldwide. The cardiac extracellular matrix not only provides structural support, but also is a core aspect of the myocardial response to various biomechanical stresses and heart failure. MFAP4 (microfibrillar‐associated protein 4) is an integrin ligand located in the extracellular matrix, whose biological functions in the heart remain poorly understood. In the current study we aimed to test the role of MFAP4 in cardiac remodeling. Methods and Results MFAP4‐deficient (MFAP4−/−) and wild‐type mice were subjected to aortic banding surgery and isoproterenol to establish models of cardiac remodeling. We also evaluated the functional effects of MFAP4 on cardiac hypertrophy, fibrosis, and cardiac electrical remodeling. The expression of MFAP4 was increased in the animal cardiac remodeling models induced by pressure overload and isoproterenol. After challenge of 8 weeks of aortic banding or 2 weeks of intraperitoneal isoproterenol, MFAP4−/− mice exhibited lower levels of cardiac fibrosis and fewer ventricular arrhythmias than wild‐type mice. However, there was no significant effect on cardiomyocyte hypertrophy. In addition, there was no significant difference in cardiac fibrosis severity, hypertrophy, or ventricular arrhythmia incidence between wild‐type‐sham and knockout‐sham mice. Conclusions These findings are the first to demonstrate that MFAP4 deficiency inhibits cardiac fibrosis and ventricular arrhythmias after challenge with 8 weeks of aortic banding or 2 weeks of intraperitoneal isoproterenol but does not significantly affect the hypertrophy response. In addition, MFAP4 deficiency had no significant effect on cardiac fibrosis, hypertrophy, or ventricular arrhythmia in the sham group in this study.

AIM: To investigate the effect of cultured limbal stem cells on proliferating of vascular endothelial cells and validate the theory of limbal stem cells.METHODS: The limbal stem cells and epithelium cells of bulbar conjunctiva were cultured and determined by immunohistochemistry staining with AE-5. The supernatant was collected and added into the cultured human umbilical vein endothelium cells(ECV-304). The negative control was set up. After 24h, MTT was done to detect endothelium cell proliferation. The statistical analysis was done by analysis of Variance.RESULTS: Negative stain of AE-5 can be seen in limbal stem cells and positive stain can be seen in conjunctiva cells. The ratio of MTT added by limbal stem cell supernatant, conjunctiva epithelium cell and negative control were 2.097±0.079, 1.981±0.034 and 1.990±0.044, respectively. There were significant difference among the three groups(F=9.169, P=0.000). The proliferate activity of vascular endothelial cells added by supernatant of limbal stem cells was higher than the other two groups(P=0.005 and P=0.007, respectively).CONCLUSION:The supernatant of limbal stem cells can improve the proliferation of vascular endothelium cell. This may be the unique characteristics of limbal stem cells. This study provides more evidences for the theory of limbal stem cells by determining the functional methods.