BACKGROUND:The long-term patency rate of synthetic blood vessels remains a significant challenge that requires urgent attention.Enhancing the anticoagulant performance of small-caliber artificial blood vessels is crucial in ensuring their long-term efficacy.OBJECTIVE:To investigate the anticoagulation activity of polycaprolactone/low molecular weight fucoidan nanofibers with shell core structure and determine the effect on the activity of human umbilical vein endothelial cells.METHODS:Polycaprolactone nanofiber membranes and polycaprolactone/low molecular weight fucoidan nanofiber membranes with polycaprolactone as shell layer and low molecular weight fucoidan as core layer were prepared by emulsion electrospinning method(the mass ratio of low molecular weight fucoidan to polycaprolactone was 10％,25％,40％,and 55％,respectively).The morphology and structure of the fibers were characterized by scanning electron microscopy,fluorescence microscopy,and infrared spectroscopy.The mechanical strength of the fiber membranes was detected by tensile test.The loading rate and sustained release rate of low molecular weight fucoidan in the nanofibers were detected by 1,9-dimethylmethylene blue dye.The anticoagulant properties of the fiber membranes were verified by hemolysis test,dynamic coagulation test,plasma recalcification test,and platelet adhesion test.The five fiber membranes were co-cultured with human umbilical vein endothelial cells.The cell proliferation was detected by CCK-8 assay and the cell morphology was observed by fluorescence microscopy.RESULTS AND CONCLUSION:(1)Scanning electron microscope showed that the surface of polycaprolactone/low molecular weight brown algae polysaccharide nanofiber membrane was smooth,the fiber diameter was uniform,and there was no obvious beaded structure.With the increase of low molecular weight brown algae polysaccharide content in the fiber membrane,the diameter of the fiber membrane increased and the maximum tensile stress decreased,but it still met the mechanical properties requirements of small-caliber artificial blood vessels.Fluorescence images and infrared spectra confirmed that low molecular weight brown algae polysaccharide was successfully loaded into polycaprolactone nanofiber membrane,and the low molecular weight brown algae polysaccharide loaded in each group of fiber membranes was released suddenly within 12 hours and released at a relatively low rate after 48 hours.(2)Compared with polycaprolactone nanofiber membrane,polycaprolactone/low molecular weight brown algae polysaccharide nanofiber membrane had better anticoagulant activity,among which the group with a mass ratio of low molecular weight brown algae polysaccharide to polycaprolactone of 25％had the best anticoagulant effect.All five fiber membranes supported the growth and proliferation of human umbilical vein endothelial cells without affecting cell morphology and had no obvious cytotoxicity.(3)The results show that the polycaprolactone/low molecular weight brown algae polysaccharide nanofiber membrane has good anticoagulant function,blood compatibility,and cell compatibility.

BACKGROUND:The long-term patency rate of synthetic blood vessels remains a significant challenge that requires urgent attention.Enhancing the anticoagulant performance of small-caliber artificial blood vessels is crucial in ensuring their long-term efficacy.OBJECTIVE:To investigate the anticoagulation activity of polycaprolactone/low molecular weight fucoidan nanofibers with shell core structure and determine the effect on the activity of human umbilical vein endothelial cells.METHODS:Polycaprolactone nanofiber membranes and polycaprolactone/low molecular weight fucoidan nanofiber membranes with polycaprolactone as shell layer and low molecular weight fucoidan as core layer were prepared by emulsion electrospinning method(the mass ratio of low molecular weight fucoidan to polycaprolactone was 10％,25％,40％,and 55％,respectively).The morphology and structure of the fibers were characterized by scanning electron microscopy,fluorescence microscopy,and infrared spectroscopy.The mechanical strength of the fiber membranes was detected by tensile test.The loading rate and sustained release rate of low molecular weight fucoidan in the nanofibers were detected by 1,9-dimethylmethylene blue dye.The anticoagulant properties of the fiber membranes were verified by hemolysis test,dynamic coagulation test,plasma recalcification test,and platelet adhesion test.The five fiber membranes were co-cultured with human umbilical vein endothelial cells.The cell proliferation was detected by CCK-8 assay and the cell morphology was observed by fluorescence microscopy.RESULTS AND CONCLUSION:(1)Scanning electron microscope showed that the surface of polycaprolactone/low molecular weight brown algae polysaccharide nanofiber membrane was smooth,the fiber diameter was uniform,and there was no obvious beaded structure.With the increase of low molecular weight brown algae polysaccharide content in the fiber membrane,the diameter of the fiber membrane increased and the maximum tensile stress decreased,but it still met the mechanical properties requirements of small-caliber artificial blood vessels.Fluorescence images and infrared spectra confirmed that low molecular weight brown algae polysaccharide was successfully loaded into polycaprolactone nanofiber membrane,and the low molecular weight brown algae polysaccharide loaded in each group of fiber membranes was released suddenly within 12 hours and released at a relatively low rate after 48 hours.(2)Compared with polycaprolactone nanofiber membrane,polycaprolactone/low molecular weight brown algae polysaccharide nanofiber membrane had better anticoagulant activity,among which the group with a mass ratio of low molecular weight brown algae polysaccharide to polycaprolactone of 25％had the best anticoagulant effect.All five fiber membranes supported the growth and proliferation of human umbilical vein endothelial cells without affecting cell morphology and had no obvious cytotoxicity.(3)The results show that the polycaprolactone/low molecular weight brown algae polysaccharide nanofiber membrane has good anticoagulant function,blood compatibility,and cell compatibility.

AIM: To investigate the relationship between serum levels of sirtuins(Sirts)1-6 and oxidative stress markers, and to evaluate their diagnostic value for age-related cataract(ARC).METHODS:A prospective cohort of ARC patients admitted to the hospital between June 2019 and July 2021 was enrolled as the study subjects. Concurrently, age-matched healthy individuals undergoing routine physical examinations at the hospital during the same period were recruited as the control group. Baseline demographic and clinical characteristics were compared between the two groups. Serum levels of Sirt1-6 and oxidative stress markers including malondialdehyde(MDA), superoxide dismutase(SOD), glutathione peroxidase(GSH-Px), and total antioxidant capacity(TAC)were compared. Pearson correlation analysis was performed to assess the associations between serum Sirt1-6 levels and oxidative stress parameters. Multivariate Logistic regression analysis was conducted to analysis risk factors associated with ARC occurrence. Receiver operating characteristic(ROC)curve was used to evaluate the diagnostic value of serum Sirt1-6 levels and oxidative stress indicators for ARC.RESULTS: The study included 127 ARC patients, comprising 68 men and 59 women, with a mean age of 66.05±2.58 y; the concurrent control group consisted of 121 patients, comprising 63 men and 58 women, with a mean age of 65.54±2.86 y. Serum levels of Sirt1, 3 and 6, SOD, GSH-Px, and TAC were significantly lower in the ARC group compared to the control group(all P<0.001), whereas MDA levels were markedly elevated(P<0.001). Pearson correlation analysis revealed that serum levels of Sirt1, Sirt3, Sirt6 in the ARC group were positively correlated with SOD, GSH-Px, and TAC, and negatively correlated with MDA. Multivariate Logistic regression analysis demonstrated that serum Sirt1, Sirt6, MDA, SOD, and GSH-Px were significantly associated with the occurrence of ARC(all P<0.001). ROC curve analysis showed that the combination of Sirt1, Sirt6, MDA, SOD, and GSH-Px yielded an area under the curve(AUC)of 0.995 for diagnosing ARC, which was significantly higher than that of Sirt1 alone(Z=4.978,P<0.001), Sirt6 alone(Z=7.487,P<0.001), MDA alone(Z=6.449,P<0.001), SOD alone(Z=5.773,P<0.001), or GSH-Px alone(Z=5.056,P<0.001), indicating superior diagnostic accuracy of the multimarker panel(P<0.05). CONCLUSION: Serum levels of Sirt1, 3, and 6 are generally reduced in ARC patients and are closely associated with oxidative stress imbalance. Specifically, decreased serum levels of Sirt1 and Sirt6, along with oxidative stress markers(elevated MDA and reduced SOD and GSH-Px)are identified as risk factors for ARC. Moreover, the combined detection of these indicators presents high diagnostic value for ARC.

Objective: To investigate the effects of "liver-smoothing and spirit-regulating" acupuncture on the intestinal flora, lipopolysaccharide (LPS) and the hippocampal toll-like receptor 4 (TLR4)/ transcription factor (NF)-κB signaling pathway in depressive disorder mouse model, and to explore its underlying mechanisms. Methods: Eighteen male SPF-grade C57BL/6J mice were randomly assigned to the control, model, and acupuncture groups using a random number method, with six mice in each group. The depression disorder model was induced in mice from both the acupuncture and model groups using CUMS. The mice in the acupuncture group were treated with acupuncture at the acupoints of "Baihui" (DU20), "Yintang" (DU29), "Hegu" (LI4), and "Taichong" (LR3) on the 15th day of modeling, with a duration of 20 min per session, once per day, for 2 consecutive weeks. Behavioral differences were assessed using the sucrose preference test, open field test, and forced swim test. Hematoxylin-eosin staining was used to observe pathological changes in the hippocampus and colon. The levels of the inflammatory factors interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and LPS in the hippocampus and colon were measured using Enzyme-linked Immunosorbent Assay. Western blotting was used to detect the expression of TLR4 and NF-κB protein in the hippocampus. Changes in gut microbiota structure and abundance were analyzed by 16 S rDNA sequencing. Results: Compared to the control group, the model group showed reduced sucrose preference rate, time in the center area, and total distance, with an increase in immobility time (P<0.01). Inflammatory pathological changes were observed in the hippocampal CA1 region and colon. The contents of IL-1β, IL-6, TNF-α, and LPS in the hippocampus and colon increased (P<0.01). The protein expression levels of hippocampal TLR4 and NF-κB were increased (P<0.01). The Chao1 index was increased (P<0.01). The relative abundances of Pseudomonadales, Acinetobacter, Moraxellaceae, Solibacillus, Escherichia_shigella, Enterobacteriaceae, Enterobacterales, Dubosiella, and Erysipelottichales were decreased, while the relative abundances of Alloprevotella and gram_negative_bacteriurh_cTPY_13 were increased (P<0.05). The pathways of lipopolysaccharide biosynthesis and pathogenic Escherichia coli infection were upregulated, and the pathway of terpenoid backbone biosynthesis was downregulated (P<0.01). Compared to the model group, the acupuncture group showed increased sucrose preference, time in the center area, and total distance, with a decrease in immobility time (P<0.01). The inflammatory pathological changes in the hippocampal CA1 region and colon were alleviated. The contents of IL-1β, IL-6, TNF-α, and LPS in the hippocampus and colon were reduced(P<0.01). The protein expression levels of hippocampal TLR4 and NF-κB were reduced (P<0.01). The Chao1 index was decreased (P<0.05), and the relative abundances of Dubosiella and Erysipelotrichaceae were increased, while the relative abundance of Rikenellaceae, Alloprevotella, and gram_negative_bacteriuch_cTPY_13 were decreased(P<0.05). The pathways of lipopolysaccharide biosynthesis and pathogenic Escherichia coli infection were significantly downregulated, and the pathway of terpenoid backbone biosynthesis was upregulated (P<0.01). Conclusion " Liver-smoothing and spirit-regulating" acupuncture can improve depressive symptoms in depressive disorder mice, potentially through regulating the LPS and TLR4/NF-κB signaling pathway mediated by intestinal flora, reducing the inflammatory response of the hippocampus, and improving the pathological injury of the hippocampus.

Traditional development of small protein scaffolds has relied on display technologies and mutation-based engineering, which limit sequence and functional diversity, thereby constraining their therapeutic and application potential. Protein design tools have significantly advanced the creation of novel protein sequences, structures, and functions. However, further improvements in design strategies are still needed to more efficiently optimize the functional performance of protein-based drugs and enhance their druggability. Here, we extended an evolution-based design protocol to create a novel minibinder, BindHer, against the human epidermal growth factor receptor 2 (HER2). It not only exhibits super stability and binding selectivity but also demonstrates remarkable properties in tissue specificity. Radiolabeling experiments with ^99mTc, ⁶⁸Ga, and ¹⁸F revealed that BindHer efficiently targets tumors in HER2-positive breast cancer mouse models, with minimal nonspecific liver absorption, outperforming scaffolds designed through traditional engineering. These findings highlight a new rational approach to automated protein design, offering significant potential for large-scale applications in therapeutic mini-protein development.

Inflammatory bowel disease (IBD), a chronic inflammatory condition of the gastrointestinal tract, is associated with a significantly increased risk of both venous and arterial thromboembolism. Common risk factors for thrombosis include disease activity, surgery, older age, central venous catheterization, etc. However, thrombotic events related to pharmacological treatment are often under-recognized, despite their potential for severe consequences. With the rapid expansion of therapeutic options for IBD in recent years, it has become increasingly important to acknowledge that different agents carry varying levels of thrombotic risk. This review summarizes current evidence on the thrombotic risks associated with IBD therapies and outlines preventive strategies, aiming to optimize the thrombosis risk management and reduce treatment-related thrombotic events in IBD patients.

Abdominal obesity represents the predominant obesity phenotype in China.Compared to peripheral obesity,individuals with abdominal obesity are more prone to metabolic disorders,cardiovascular diseases,and higher mortality rates.Catgut embedding therapy at acupoints has demonstrated significant clinical efficacy in preventing and treating abdominal obesity.However,standardized clinical guidelines for its application in abdominal obesity management have not yet been established.This review comprehensively summarizes the clinical applications of catgut embedding therapy for simple abdominal obesity and abdominal obesity with various complications,aiming to provide clinical evidence and theoretical guidance for its use in preventing and treating abdominal obesity.

AIM: To investigate the effect of corneal topography-guided phacoemulsification with transparent corneal incision on cataract patients.METHODS:A total of 92 cataract patients(92 eyes)admitted to our hospital from February 2021 to February 2023 were prospectively selected and randomly divided into two groups: the control group(46 eyes)received the conventional 11:00 clear corneal incision scheme, and the study group(46 eyes)received the steepest meridian clear corneal incision scheme. The uncorrected visual acuity, corneal surface morphology indicators, including surface regularity index(SRI), surface asymmetry index(SAI), and cylinder(CYL), subjective dry eye symptoms questionnaire scoring scale(SDES), tear film break-up time(BUT), and complications were compared between the two groups.RESULTS:All patients completed the follow-up. The uncorrected visual acuity of the study group was significantly better than that of the control group at 1 wk, 1 and 3 mo after surgery(all P<0.05); there were statistical significance in the SAI and CYL of both groups of patients at 3 mo after surgery(all P<0.05); the fluctuation levels of SDES and BUT in the study group were significantly lower than those in the control group at different time points after surgery(all P<0.05); and there was no statistical difference in complications between the two groups(P>0.05).CONCLUSION:Under the guidance of corneal topography, phacoemulsification through the transparent corneal incision of the steepest meridian of the cornea can improve the uncorrected visual acuity of cataract patients, restore the corneal surface morphology, and have few complications.

AIM: To investigate the effect of corneal topography-guided phacoemulsification with transparent corneal incision on cataract patients.METHODS:A total of 92 cataract patients(92 eyes)admitted to our hospital from February 2021 to February 2023 were prospectively selected and randomly divided into two groups: the control group(46 eyes)received the conventional 11:00 clear corneal incision scheme, and the study group(46 eyes)received the steepest meridian clear corneal incision scheme. The uncorrected visual acuity, corneal surface morphology indicators, including surface regularity index(SRI), surface asymmetry index(SAI), and cylinder(CYL), subjective dry eye symptoms questionnaire scoring scale(SDES), tear film break-up time(BUT), and complications were compared between the two groups.RESULTS:All patients completed the follow-up. The uncorrected visual acuity of the study group was significantly better than that of the control group at 1 wk, 1 and 3 mo after surgery(all P<0.05); there were statistical significance in the SAI and CYL of both groups of patients at 3 mo after surgery(all P<0.05); the fluctuation levels of SDES and BUT in the study group were significantly lower than those in the control group at different time points after surgery(all P<0.05); and there was no statistical difference in complications between the two groups(P>0.05).CONCLUSION:Under the guidance of corneal topography, phacoemulsification through the transparent corneal incision of the steepest meridian of the cornea can improve the uncorrected visual acuity of cataract patients, restore the corneal surface morphology, and have few complications.

AIM:To investigate the role and mechanism of the glucagon-like peptide-1 receptor agonist lira-glutide(Lira)in regulating ferroptosis of mouse insulinoma MIN6 cells induced by high glucose and high fat.METHODS:The mouse insulinoma MIN6 cells were exposed to 30 mmol/L glucose and 500 μmol/L palmitic acid to establish an islet β cell injury model.On this basis,a ferroptosis inducer erastin,a ferroptosis inhibitor ferrostatin-1(Fer-1),and low and high concentrations of Lira were administered.Cell viability of different treatment groups were detected by CCK-8 assay.The malondialdehyde(MDA)kit was used to determine the changes in intracellular MDA content.The reactive oxygen species(ROS)kit was used to detect the changes in the ROS level of cells.The Fe2+fluorescence probe FerroOrange and mitochondrial membrane potential(JC-1)were used to detect the intracellular Fe2+levels and mitochondrial functions in different treatment groups.The mouse insulin ELISA kit was used to detect the insulin secretion of cells.RT-qPCR was used to detect the changes in the expression levels of key ferroptosis genes and insulin secretion genes in different treat-ment groups.Western blot was used to detect the expression levels of key ferroptosis proteins,glutathione peroxidase 4(GPX4)and solute carrier family 7 member 11(SLC7A11)in different treatment groups.RESULTS:Compared with the cells treated with high glucose and high fat,after treatment with Fer-1 and high-dose Lira,the cell viability,insulin secre-tion of the cells,and mitochondrial membrane potential all increased significantly,the levels of ROS,MDA and Fe2+were decreased(P<0.05).The results of RT-qPCR showed that Fer-1 and high-dose Lira significantly upregulated the expres-sion of genes promoting insulin secretion(P<0.05).The results of Western blot showed that Fer-1 and high-dose Lira sig-nificantly upregulated the expression of ferroptosis-inhibiting proteins GPX4 and SLC7A11(P<0.05).CONCLUSION:Liraglutide inhibits ferroptosis of mouse insulinoma MIN6 cells by regulating the SLC7A11/GPX4 signaling pathway,there-by improving the damage and dysfunction of MIN6 cells induced by high glucose and high fat.