Accommodative dysfunction, particularly accommodative lag, acts as a core hub connecting near work activity to myopic axial elongation. This review thoroughly explores the multidimensional biological mechanisms by which accommodative function drives axial growth. In addition to the classic pathway where hyperopic defocus signals induce retinal-choroidal-scleral biochemical remodeling, two other mechanisms are highlighted: a biomechanical pathway involving direct mechanical traction on the equatorial sclera caused by sustained ciliary muscle contraction, and a neural pathway where abnormal accommodative micro fluctuations degrade retinal image quality, thereby triggering abnormal ocular growth. Based on these comprehensive mechanisms, this paper systematically analyzes the principles of pharmacological(atropine), optical(orthokeratology, defocus lenses), and vision therapy interventions. Myopia progression results from the integrated regulation of optical defocus, mechanical stress, and neural dynamics. Future myopia control should advance toward precise, personalized combination strategies tailored to individual accommodative and genetic profiles.

BACKGROUND: The main cause of restenosis after percutaneous transluminal angioplasty (PTA) is the excessive proliferation and migration of vascular smooth muscle cells (VSMCs). Lin28a has been reported to play critical regulatory roles in this process. However, whether CCAAT/enhancer-binding proteins β (C/EBPβ) binds to the Lin28a promoter and drives the progression of restenosis has not been clarified. Therefore, in the present study, we aim to clarify the role of C/EBPβ-Lin28a axis in restenosis. METHODS: Restenosis and atherosclerosis rat models of type 2 diabetes ( n   =  20, for each group) were established by subjecting to PTA. Subsequently, the difference in DNA methylation status and expression of C/EBPβ between the two groups were assessed. EdU, Transwell, and rescue assays were performed to assess the effect of C/EBPβ on the proliferation and migration of VSMCs. DNA methylation status was further assessed using Methyltarget sequencing. The interaction between Lin28a and ten-eleven translocation 1 (TET1) was analysed using co-immunoprecipitation (Co-IP) assay. Student's t -test and one-way analysis of variance were used for statistical analysis. RESULTS: C/EBPβ expression was upregulated and accompanied by hypomethylation of its promoter in restenosis when compared with atherosclerosis. In vitroC/EBPβ overexpression facilitated the proliferation and migration of VSMCs and was associated with increased Lin28a expression. Conversely, C/EBPβ knockdown resulted in the opposite effects. Chromatin immunoprecipitation assays further demonstrated that C/EBPβ could directly bind to Lin28a promoter. Increased C/EBPβ expression and enhanced proliferation and migration of VSMCs were observed after decitabine treatment. Further, mechanical stretch promoted C/EBPβ and Lin28a expression accompanied by C/EBPβ hypomethylation. Additionally, Lin28a overexpression reduced C/EBPβ methylation via recruiting TET1 and enhanced C/EBPβ-mediated proliferation and migration of VSMCs. The opposite was noted in Lin28a knockdown cells. CONCLUSION Our findings suggest that the C/EBPβ-Lin28a axis is a driver of restenosis progression, and presents a promising therapeutic target for restenosis.
Animals ; Cell Proliferation/genetics* ; Cell Movement/genetics* ; Muscle, Smooth, Vascular/metabolism* ; Rats ; DNA Methylation/physiology* ; CCAAT-Enhancer-Binding Protein-beta/genetics* ; Male ; Myocytes, Smooth Muscle/cytology* ; Rats, Sprague-Dawley ; RNA-Binding Proteins/genetics* ; Cells, Cultured ; Coronary Restenosis/metabolism*

Computational modeling is an invaluable tool for mechanism analysis, directed engineering, and rational design of biological parts, metabolic networks, and even cellular systems. It can provide new technological solutions to address biological challenges at different levels and has become a central focus of research in biomanufacturing. In the computational modeling of proteins, which are the key parts in biological systems, the traditional physics-based methods (computer software and mathematical model) have been widely used to study the physical and chemical processes in the functioning of proteins, and have thus been recognized as a powerful tool for understanding complex biological systems and guiding experimental designs. As the scale of computational modeling continues to expand, traditional modeling techniques face difficulties in balancing computational accuracy and speed. In recent years, the explosive growth of biological data has made it possible to construct high-performance artificial intelligence (AI) models, which brings new opportunities to the computational modeling of proteins, and the AI-enhanced physics-based computational modeling technologies have emerged. This combined strategy not only incorporates the chemical knowledge and established physical principles but also is powerful in data processing and pattern recognition, which greatly improves the computational efficiency and prediction accuracy, as well as possesses stronger interpretation ability, transferability, and robustness. The AI-enhanced physics-based computational modeling technologies have already shown great potential and value in biocatalysis, paving a new way for the future development of biomanufacturing.
Artificial Intelligence ; Proteins/chemistry* ; Computer Simulation ; Software ; Computational Biology/methods*

BACKGROUND: The association between uric acid-albumin ratio (UAR) with different diseases has been evaluated before. However, the association between UAR with spontaneous reperfusion (SR) in patients with ST-segment elevation myocardial infarction (STEMI) has not been explored. METHODS: STEMI patients admitted to our department and underwent primary coronary angiography between 1^st November 2018 and 31^st December 2020 were retrospectively enrolled. The patients were divided into the SR group and the non-SR group according to the index coronary angiography results. The association between UAR and SR was evaluated by uni-variable and multi-variable logistic analysis. Receiver operating characteristic curve analysis was used to determine the optimum cut-off level of UAR in predicting SR. RESULTS: Three hundred and fifty-seven patients were finally enrolled in our study, 55 patients were divided into the SR group and 302 patients were divided into the non-SR group. In uni-variable analysis, patients with SR were older (P = 0.032), with higher red blood cell distribution width (P < 0.001) and red blood cell distribution width-to-platelet ratio (P < 0.001), higher level of C-reactive protein (P = 0.046), higher level of uric acid (P < 0.001) compared with patients without SR. Patients with SR had a lower level of platelets (P = 0.008), lower level of on-admission B-type natriuretic peptide (P < 0.001). As for the level of UAR, STEMI patients with SR had significantly higher levels of UAR compared with STEMI patients without SR [11.1 (8.9-13.4) vs. 8.3 (6.6-10.0), P < 0.001]. Further multi-variable logistic analysis reveals that UAR was the independent risk factor of SR in different models after adjusting different variables. Receiver operating characteristic analysis showed that UAR had good predictive value in SR (AUC = 0.75, 95% CI: 0.702-0.794, P < 0.01). CONCLUSIONS Our study shows that UAR is an independent risk factor for predicting SR in STEMI patients.

Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction

Objective:Based on a single-center retrospective study,to explore the efficacy of intervertebral fusion through different approaches combined with pedicle screw internal fixation in the treatment of single-segment low-grade lumbar spondylolisthesis.Methods:This study retrospectively analyzed the clinical data of 87 patients with single-segment low-grade lumbar spondylolisthesis who were treated in our hospital from January 2021 to August 2022,the cases were divided into Group A(41 cases)and Group B(46 cases)according to the differences in surgical methods.Group A received treatment with posterior lumbar interbody fusion(PLIF)combined with pedicle screw internal fixation,while Group B received treatment with percutaneous endoscopic posterior lumbar interbody fusion(PE-PLIF)combined with pedicle screw internal fixation.Both groups were followed up for two years.The Visual Analogue Scale(VAS)scores of the waist and legs,perioperative indicators,recovery of lumbar function[Japanese Orthopaedic Association(JOA)score,Oswestry Disability Index(ODI)score],and serum inflammatory mediators levels[interleukin-1α(IL-1α),transforming growth factor β1(TGF-β1),interleukin-6(IL-6)],the rate of lumbar interbody fusion,the rate of lumbar spondylolisthesis and the incidence of postoperative complications of the two groups were compared.Results:The operation time and the number of intraoperative X-ray fluoroscopy sessions in group B were both more than those in group A,while the hospital stay,the intraoperative blood loss and total incision length in Group B were all shorter than those in group A(P＜0.05).The VAS scores of the waist and legs in both groups decreased at 3 d after operation and the last follow-up(P＜0.05),and the VAS scores of the waist and legs in group B were lower than those in group A(P＜0.05).The ODI scores of both groups decreased at 3 d after operation and the last follow-up,and the ODI scores of group B were lower than those in group A;The JOA score increased,and the JOA scores of group B were all higher than those in group A(P＜0.05).Serum IL-1α,TGF-β1 and IL-6 levels in both groups decreased at 3 d and 7 d after operation,and serum IL-1α,TGF-β1 and IL-6 levels in group B were all lower than those in group A(P＜0.05).There was no statistically significant difference in the incidence of complications,the rate of lumbar interbody fusion,and the rate of lumbar spondylolisthesis between the two groups(P＞0.05).Conclusion:Compared with PLIF,PE-PLIF combined with pedicle screw internal fixation in the treatment of single-segment low-grade lumbar.spondylolisthesis,can better relieve the degree of pain of the waist and legs,improve lumbar dysfunction,regulate serum inflammatory mediators levels more effectively,and has higher safety and significant therapeutic efficacy.

Objective To explore the effect of evening primrose oil(EPO)on aortic endothelial damage in rats with polycystic ovary syndrome(PCOS),using network pharmacology and in vivo experiments.Methods The potential targets of EPO for improving aortic endothelial injury in PCOS rats were predicted by network pharmacology,and the selected core targets and renin-angiotensin signaling(RAS)pathway were verified by experiments.Fifty-eight female SD rats were divided randomly into a blank group(n=10)and a modeling group(n=48).Rats in the blank group were fed a normal diet and rats in the modeling group received a high-fat diet for 8 weeks.The PCOS model was prepared at week 6 by administration of letrozole(1 mg/(kg·d))for 21 days.Blood was taken from the tail vein after modeling and serum was collected to detect hormone levels.The model rats were then divided randomly into four groups and treated with the corresponding drugs for 6 weeks.Blood,blood vessels,and ovaries were then collected.Tissue morphology was examined by hematoxylin and eosin staining and serum levels of luteinizing hormone(LH),testosterone(T),follicle-stimulating hormone(FSH),endothelin(ET-1),and tumor necrosis factor(TNF-α)were detected by enzyme-linked immunosorbent assay(ELISA).Serum levels of nitric oxide(NO)were determined by spectrophotometry.Protein expression levels of core targets and RAS pathway-related factors were assessed by western blotting and immunohistochemistry.Results Twenty-five intersection targets of EPO and PCOS were identified by network pharmacological analysis.Kyoto encyclopedia of genes and genomes analysis showed that EPO improved vascular injury in PCOS rats via multiple pathways,including RAS.Serum levels of ET-1,FSH,LH,and T measured by ELISA were significantly decreased after EPO treatment,compared with the model group(P＜0.01).EPO significantly decreased the expression levels of Ang Ⅰ,VEGF-B,AT2R,ET-1,and TNF-α proteins in the aorta(P＜0.01)and significantly increased expression levels of Ang Ⅱ,CD31,and endothelial NO synthase proteins(P＜0.01).Conclusions EPO may ameliorate vascular endothelial injury in PCOS model rats by inhibiting the RAS signaling pathway and by overactivation of the ACE/Ang Ⅱ/AT1 axis.

Objective To explore the effect of evening primrose oil(EPO)on aortic endothelial damage in rats with polycystic ovary syndrome(PCOS),using network pharmacology and in vivo experiments.Methods The potential targets of EPO for improving aortic endothelial injury in PCOS rats were predicted by network pharmacology,and the selected core targets and renin-angiotensin signaling(RAS)pathway were verified by experiments.Fifty-eight female SD rats were divided randomly into a blank group(n=10)and a modeling group(n=48).Rats in the blank group were fed a normal diet and rats in the modeling group received a high-fat diet for 8 weeks.The PCOS model was prepared at week 6 by administration of letrozole(1 mg/(kg·d))for 21 days.Blood was taken from the tail vein after modeling and serum was collected to detect hormone levels.The model rats were then divided randomly into four groups and treated with the corresponding drugs for 6 weeks.Blood,blood vessels,and ovaries were then collected.Tissue morphology was examined by hematoxylin and eosin staining and serum levels of luteinizing hormone(LH),testosterone(T),follicle-stimulating hormone(FSH),endothelin(ET-1),and tumor necrosis factor(TNF-α)were detected by enzyme-linked immunosorbent assay(ELISA).Serum levels of nitric oxide(NO)were determined by spectrophotometry.Protein expression levels of core targets and RAS pathway-related factors were assessed by western blotting and immunohistochemistry.Results Twenty-five intersection targets of EPO and PCOS were identified by network pharmacological analysis.Kyoto encyclopedia of genes and genomes analysis showed that EPO improved vascular injury in PCOS rats via multiple pathways,including RAS.Serum levels of ET-1,FSH,LH,and T measured by ELISA were significantly decreased after EPO treatment,compared with the model group(P＜0.01).EPO significantly decreased the expression levels of Ang Ⅰ,VEGF-B,AT2R,ET-1,and TNF-α proteins in the aorta(P＜0.01)and significantly increased expression levels of Ang Ⅱ,CD31,and endothelial NO synthase proteins(P＜0.01).Conclusions EPO may ameliorate vascular endothelial injury in PCOS model rats by inhibiting the RAS signaling pathway and by overactivation of the ACE/Ang Ⅱ/AT1 axis.

Objective:To explore associated factors of post-discharge depressive symptom severity in patients with bipolar disorder.Methods:A longitudinal follow-up was conducted to investigate the demographic,behavioral,and clinical characteristics,and social function among discharged patients with bipolar disorder who met the DSM-5 diagnostic criteria.Clinical characteristics were assessed with the Hamilton Depression Scale(HAMD)and Brief Psychiatric Rating Scale(BPRS).Single factor and multivariate regression were carried out to explore the associat-ed factors of depressive symptom severity in patients with bipolar disorder.Results:A total of 298 discharged pa-tients with bipolar disorder were face-to-face interviewed to complete the follow-up survey.At follow-up time,psy-chotic symptoms(standardized(β)=0.18),housework((β)=0.23),social interaction((β)=0.17)and BPRS total score((β)=0.46)were positively associated with HAMD total score.Productive labor and work((β)=-0.27)and person-al life management((β)=-0.15)were negatively associated with HAMD total scores.Conclusion:Post-discharge depressive symptom severity in bipolar disorder patients is influenced by multiple factors.Effective management of psychotic symptoms,combined with enhanced community-based social rehabilitation and functional recovery,may help reduce the persistence or worsening of depressive symptoms and improve prognosis.

Aim To explore the mechanism of the effect of siRNA-mediated MAGE-3 silencing on intesti-nal flora,gastric mucosal PTEN expression and liver metastasis in rats with gastric cancer based on MAPK/ERK signaling pathway.Methods Thirty rats were randomly divided into the normal(CO)group,model(MO)group,and MAGE-3 silenced(SM)group,with 10 rats in each group.The model of MO group and SM group was established by MNNG gavage meth-od.After successful modeling,the SM group was intri-toneally injected with 20 μg·kg-1 shRNA MAGE-3 lentiviral vector.The number of intestinal flora in rats was detected by selective medium of intestinal flora,the expression of PTEN in gastric mucosa was detected by immunohistochemistry,liver metastasis was detected by HE staining,and the protein expression of MAPK/ERK signaling pathway was detected by Western blot.The regulatory effect of siRNA-mediated MAGE-3 si-lencing on MAPK/ERK signaling pathway was verified in vitro.Results Compared with CO group,the con-tents of Enterococcus and Escherichia coli,the protein expressions of P-MEK1,P-ERK1 and P-ELK1 in MO group increased(P＜0.05),while the contents of Lactobacillus and Bifidobacterium and the expression of PTEN decreased(P＜0.05).In SM group,the con-tents ofEnterococcus,Escherichiacoli,P-MEK1,P-ERK1 and P-ELK1 protein expressions decreased(P＜0.05),while the contents of Lactobacillus,Bifidobac-terium and PTEN expression increased(P＜0.05).Compared with group CO,the protein expressions of P-MEK1,p-ERK1 and P-ELK1 in group MO were not significantly different(P＞0.05),while the protein expressions of P-MEK1,p-ERK1 and P-ELK1 in group SM were reduced compared with group MO(P＜0.05).Conclusions siRNA-mediated MAGE-3 si-lencing can significantly improve intestinal flora,pro-mote the expression of PTEN in gastric mucosa,and inhibit liver metastasis in rats with gastric cancer.The mechanism may be related to the inhibition of MAPK/ERK signaling pathway.