Objective To explore the mechanism by which breast cancer-derived LncRNA OIP5-AS1 regulates the migration, invasion, and epithelial-mesenchymal transition of breast cancer cells through the M2 polarization of tumor-associated macrophages (TAM). Methods MDA-MB-231 cells were divided into the control group (blank control), the NC group (transfected with NC siRNA), and the si-OIP5 group (transfected with LncRNA OIP5-AS1 siRNA). The mRNA expression levels of LncRNAs OIP5-AS1, IL-4, and IL-13 were detected by RT-qPCR. The protein expression levels of IL-4 and IL-13 in the culture supernatant were detected by ELISA. The culture supernatant from the control group was added to RPMI 1640 medium at different volume ratios to induce the polarization of M0 macrophages into TAMs. The mRNA expression of CD206 in TAMs was detected by RT-qPCR. M0-type macrophages were induced with the medium supernatant of the NC group/si-OIP5 group, and the expression of CD206 was detected by Western blot. Subsequently, a co-culture model of macrophage and MDA-MB-231 was constructed to evaluate the migration and invasion abilities of MDA-MB-231 cells and detect the expression changes in Vimentin, N-cadherin and E-cadherin. Results Compared with the control and NC groups, the si-OIP5 group showed significantly downregulated expression of LncRNA OIP5-AS1 (P<0.001) and significantly decreased IL-13 mRNA and protein levels (P<0.05). Meanwhile, no significant difference was observed in the expression of IL-4 among the groups. Conditioned medium induced CD206 expression in M0 macrophages in a volume-dependent manner, with the strongest effect at a 40% volume ratio (P<0.001). The CD206 protein level in the si-OIP5 group significantly decreased (P<0.01). In the co-culture system, the migration and invasion abilities of MDA-MB-231 cells in the si-OIP5 group significantly weakened (P<0.001), the expression of E-cadherin was upregulated, and the expression levels of N-cadherin and Vimentin were downregulated (both P<0.01). Conclusion Breast cancer-derived LncRNA OIP5-AS1 can induce TAM M2 polarization mediated by IL-13, thereby promoting the migration, invasion, and EMT of breast cancer cells.

ObjectiveThe widespread adoption of portable fundus cameras for primary care and community screening is hindered by limitations in current autofocus(AF) technologies. Image-based methods relying on sharpness evaluation require iterative searches, resulting in slow convergence, while projection-based techniques are susceptible to optical artifacts and calibration errors. To address these challenges, this study introduces a novel AF system based on direct wavefront sensing, designed to deliver simultaneous high speed, high precision, and operational robustness within the compact form factor essential for portable ophthalmic devices. MethodsOur approach fundamentally reimagines the AF process by directly measuring the ocular wavefront aberration. We developed a custom portable fundus camera integrating a miniaturized Shack-Hartmann wavefront sensor (SHWS) into the optical path. An 850 nm laser diode projects a point source onto the retina via oblique illumination to minimize corneal reflections. Light scattered from this spot carries the eye’s refractive error through the imaging optics and is directed to the SHWS, positioned at a plane optically conjugate to the primary color CMOS imaging sensor. A microlens array within the SHWS samples the incident wavefront, generating a pattern of focal spots on a CCD. Real-time centroid analysis of these spots provides a map of local wavefront slopes. These measurements are processed through a singular value decomposition (SVD) algorithm to fit a Zernike polynomial basis set, enabling real-time reconstruction of the wavefront phase. The defocus component (S) is extracted from the second-order Zernike coefficients, providing a direct, quantitative measure of the refractive error in diopters. This value serves as a precise error signal in a closed-loop control system, which commands a voice-coil actuated focusing lens to its null position in a single, deterministic step, eliminating the need for iterative search algorithms. ResultsComprehensive evaluation demonstrated the system’s high performance. Testing on a calibrated model eye (OEMI-7) established a highly linear relationship between the computed defocus S and the focusing lens position across a ±20 Diopter (D) compensation range, achievable within a 5 mm mechanical travel. The system achieved a focusing precision of 0.08 D, corresponding to an 18-fold improvement over a conventional projection spot-size method tested under identical conditions. The total focus acquisition time, encompassing wavefront measurement, computation, and lens actuation, averaged under 0.5 s. Clinical validation with 25 human volunteers (50 eyes, refractive range -15 D to +10 D) confirmed practical efficacy. The wavefront-sensing AF succeeded in 92% of attempts with a mean time of 0.5 s, substantially outperforming a projection-based benchmark which achieved only a 32% success rate with an average time of 4.25 s. The system provided instantaneous directional guidance and maintained stability during minor ocular movements. Objective assessment of image quality, via amplitude contrast of retinal vasculature, showed consistent and significant enhancement following AF correction across the entire tested diopter range. ConclusionThis work successfully implements and validates a direct wavefront-sensing autofocus paradigm for portable fundus cameras. By directly quantifying and compensating for the optical defocus aberration, this method bypasses the fundamental limitations of image-processing and projection-based techniques, enabling rapid, precise, and deterministic diopter compensation. The developed system delivers an exceptional combination of a wide operational range (±20 D), high accuracy (0.08 D), fast convergence (0.5 s), and a compact physical footprint. This technology provides a practical and high-performance focusing solution capable of enhancing the reliability, throughput, and diagnostic utility of portable retinal imaging in large-scale screening applications. Future efforts will be directed towards system cost optimization and performance adaptation for diverse ocular conditions.

ObjectiveTo reveal the effects of overexpression and knockdown of CDH18 gene on cervical cancer proliferation and migration levels through the Wnt/β-catenin signaling pathway in cervical cancer cells. MethodsA comprehensive analysis of CDH18-interacting molecules was performed via the bioinformatics STRING database （http：//cn.string-db.org）. Molecular docking between Wnt/β-catenin inhibitor XAV939 and β-catenin was performed using the bioinformatics tool AutoDock （http：//autodock.scripps.edu）. The effect of CDH18 on β-catenin subcellular distribution was detected by laser confocal microscopy. EdU assay， wound healing assay and Transwell assay were used to detect the effects of CDH18 gene overexpression， CDH18 gene knockdown and the XAV939 on cell proliferation and migration. Western blot was performed to measure the expression levels of Wnt/β-catenin pathway-related molecules， including β-catenin， transcription factor 4 （TCF4）， and cellular myelocytomatosis oncogene （c-Myc）， following CDH18 gene overexpression， CDH18 gene knockdown， or XAV939 treatment. ResultsIn SiHa and HeLa cells， CDH18 gene overexpression significantly increased the protein expression levels of β-catenin， TCF4 and c-Myc， decreased the protein expression of GSK-3β， and enhanced cell proliferation and migration， with statistically significant differences （P<0.05）. Conversely， CDH18 gene knockdown significantly reduced the protein expression of β-catenin， TCF4 and c-Myc， elevated GSK-3β expression， and suppressed cell proliferation and migration （P<0.05）.Treatment with XAV939 in SiHa and HeLa cells downregulated β-catenin， TCF4 and c-Myc， upregulated GSK-3β， and inhibited cell proliferation and migration， with significant differences （P<0.05）. ConclusionCDH18 promotes the proliferation and migration of cervical cancer cells via the Wnt/β-catenin signaling pathway.

ObjectiveTo investigate the effects of Ditantang on metabolic dysfunction-associated fatty liver disease （MAFLD） in rats by focusing on the regulation of glycogen synthesis mediated by the uridine diphosphate glucose （UDPG）-site-1-protease （S1P）-sterol regulatory element-binding protein （SREBP） axis. MethodsMAFLD was modeled in SD rats by feeding a high-fat diet for 12 weeks. Rats were randomized into a control group， a model group， low-， medium-， and high-dose （2.68， 5.36， and 10.72 g·kg^-1·d^-1， respectively） Ditantang groups， and a positive control （Yishanfu， 0.18 g·kg^-1·d^-1） group. Starting from week 9 of modeling， each treatment group received corresponding drug interventions via gavage. After the experiment， the serum levels of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） were measured. The levels of TG， non-esterified fatty acids （NEFA）， glycogen， glucose-6-phosphate （G6P）， glucose-1-phosphate （G1P）， and UDPG in the liver tissue samples were measured by biochemical assay kits. Liver pathological morphology and lipid/glycogen deposition were observed via hematoxylin-eosin （HE） staining， oil red O staining， and Periodic acid-Schiff （PAS） staining. Immunofluorescence assay was conducted to detect the expression and localization of phosphoglucomutase-1 （Pgm1） and UDP-glucose pyrophosphorylase 2 （Ugp2） in the rat liver. Real-time PCR and Western blot were employed to quantify mRNA and protein levels， respectively， of key glycogen synthesis enzymes （Pgm1 and Ugp2）， key lipogenesis-related transcription factor SREBP and its target genes ［acetyl-CoA carboxylase （ACC）， fatty acid synthetase （FASN）， and stearoyl-CoA desaturase （SCD1）］， as well as S1P. ResultsCompared with the control group， the model group exhibited elevated levels of TC， TG， LDL-C in the serum and TG and NEFA in the liver， decreased serum HDL-C level （P<0.01）， reduced hepatic levels of G1P， G6P， UDPG， and glycogen （P<0.01）， appearance of fat vacuoles of varying sizes and abundant red lipid droplets， with prominent lipid deposition and reduced areas of deep glycogen staining in the liver tissue， upregulated mRNA and protein levels of SREBP1， S1P， ACC， FASN， and SCD1 （P<0.01）， and downregulated mRNA and protein levels of Pgm1 and Ugp2 （P<0.01）. Compared with the model group， all doses of Ditantang reduced the levels of TC and TG in the serum and TG and NEFA in the liver， while elevating the serum HDL-C level. Additionally， medium- and high-dose Ditantang reducted the LDL-C level （P<0.05）. Ditantang at all doses increased the hepatic levels of G1P， G6P， UDPG， and glycogen， alleviated hepatic steatosis and lipid deposition， enhanced glycogen storage， downregulated the mRNA and protein levels of SREBP1， S1P， ACC， FASN， and SCD1 （P<0.05）， while upregulating the expression of Pgm1 and Ugp2 （P<0.01）. Immunofluorescence analysis revealed decreased fluorescence intensity of S1P and enhanced fluorescence intensity of Ugp2 （P<0.01）. ConclusionDitantang can regulate glycogen synthesis through the UDPG-S1P-SREBP axis to prevent and treat MAFLD.

Objective To explore the valve regurgitation status of left heart after the implantation of left ventricular assist device (LVAD) and its effect on prognosis of patients with LVAD implantation. Methods A total of 35 patients with cardiomyopathy who underwent magnetic levitation LVAD implantation at Zhongshan Hospital, Fudan University from February 2021 to July 2024 were retrospectively selected. Clinical data during hospitalization were collected, including preoperative basic data and postoperative valve regurgitation status. Telephone follow-ups were conducted to monitor patients’ survival status and transthoracic echocardiography was used to assess left valve function. Kaplan-Meier survival curves and log-rank test were employed to compare the survival rate of patients with different levels of valve regurgitation. Results The 35 patients had a mean age of (53.9±11.1) years, with 85.7% male, and 3 patients (8.6%) died during hospitalization. Preoperatively, 17 patients (48.6%) had moderate or greater mitral regurgitation, while all 35 patients had less than moderate aortic regurgitation. One month postoperatively, thirty patients were followed up, among which 24 patients (80%) had less than moderate mitral regurgitation, including 11 cases with alleviated regurgitation compared to pre-surgery; 6 patients (20%) had moderate or greater mitral regurgitation, including 4 cases with stable regurgitation and 2 cases with progression of regurgitation compared to pre-surgery; 2 patients (6.7%) had progression of aortic regurgitation to moderate or greater. The follow-up time was 1.2 (1.0, 2.1) years, with 1-year survival rate of 91.4% and 3-year survival rate of 71.1%. Survival analysis showed that the 3-year survival rate of patients with moderate or greater mitral regurgitation one month postoperatively was significantly lower than that of patients with less than moderate regurgitation (66.7% vs 83.3%, P＝0.046). Conclusions After the implantation of magnetic levitation LVAD, most patients showed improvement in mitral regurgitation, while aortic regurgitation remained unchanged. The degree of mitral regurgitation one month postoperatively is associated with prognosis.

Objective To explore the effects of vitamin D on anxiety and depression behavior and the mechanism of hippocampal inflammation in obese rats.Methods Male Wistar rats were randomly divided into 4 groups(n=12):control group(group C),obesity group(group F),low-dose vitamin D group(L-VD group),and high-dose vitamin D group(H-VD group).Group C was fed a standard diet,and the other three groups were fed a high-fat diet.After successful establishment of the rat obesity model,L-VD group and H-VD group were intraperitoneally injected with 10 μg·kg-1·d-1 and 20 μg·kg-1·d-1 vitamin D,respective-ly,and groups C and F were injected with the same volume of normal saline;relevant indexes were detected af-ter continued feeding for 6 weeks.The sucrose preference test and open field test were used to study the be-havior of rats in each group.The histopathological changes of hippocampal tissue were observed by HE stai-ning.The expression levels of TNF-α and NF-κB protein in hippocampal tissue were detected by Western blot.Results After 6 weeks of intervention,compared with group C,the serum 25(OH)D concentration,sugar-wa-ter preference rate,total distance of open field movement,number of entries into the central area,and duration of stay in the central area were significantly decreased in group F rats.The expression levels of TNF-α and NF-κB proteins in hippocampal tissues were significantly increased(P<0.05).Compared with group F,serum 25(OH)D concentration and sugar-water preference rate were significantly increased in L-VD and H-VD groups.Anxiety and depression-like behaviors in the open field were markedly improved.TNF-α and NF-κB protein levels were significantly decreased(P<0.05).Statistically significant differences were observed in all aforementioned indicators between the groups(P<0.05).HE staining revealed looser arrangement of hipp-ocampal neurons,with extensive neuronal degeneration in group F.In contrast,L-VD and H-VD groups exhib-ited tighter and more regular neuronal arrangements,with only mild edema and cytoplasmic vacuolation in some cells.No significant neuronal degeneration was observed in the H-VD group.Conclusion Reduced vita-min D levels in obese rats exacerbate anxiety-depression-like behaviors,potentially through activation of hipp-ocampal inflammatory factors.

Medical device related infections caused by bacteria are common complications in clinical practice,and preventing bacterial colonization on the surface of medical materials is one of the important challenges in the medical field.Therefore,there is an urgent need to construct medical coatings that combine antibacterial properties and biocompatibility.In this study,a γ-polyglutamic acid(γ-PGA)complex with long-chain alkyl quaternary ammonium salts formed by electrostatic and hydrophobic interactions was prepared,which was insoluble in water but soluble in organic solvents(e.g.,ethanol),and was capable of constructing antimicrobial coatings on the surfaces of medical materials in a simple and efficient manner.The bactericidal effect of the coating was verified using viable bacteria counting experiments,and the results showed that the bactericidal rate of the coated thermoplastic polyurethane(TPU)membrane against Staphylococcus aureus was greater than 99.9%compared with that of the uncoated TPU membrane.In addition,a cytotoxicity assay was performed using the L929 fibroblast and cell proliferation detection kit(CCK-8),which showed that the survival rate of L929 fibroblasts on coated TPU was greater than 90%.Meanwhile,the hemolysis rate of coated erythrocytes was tested using fresh rabbit red blood cells(RBCs),and the hemolysis rate on the coated TPU surface was 1.5%.The above results indicated that the coating had good biocompatibility.The preparation method of medical antibacterial coating reported in this study provided a new idea for preventing bacterial infections related to implantable/interventional medical devices.

BACKGROUND:Exosomes have been confirmed to be closely related to cartilage degeneration in osteoarthritis.However,the role and mechanism of exosome-derived genes in cartilage degeneration of osteoarthritis have not been fully elucidated.OBJECTIVE:Bioinformatics analyses were used to screen the genes related to cartilage degeneration in the synovial exosomes of patients with osteoarthritis,and to determine their biological functions and signaling pathways in order to provide new therapeutic targets for delaying cartilage degeneration in osteoarthritis.METHODS:Firstly,osteoarthritis-related exosome dataset GSE185059 and cartilage degeneration dataset GSE114007 were downloaded from Gene Expression Omnibus(GEO)database to screen exosome-derived cartilage degeneration related genes.GO functional and KEGG pathway enrichment analyses were performed based on the screened exosome-derived cartilage degeneration related genes.Protein-protein interaction network was drawn and Ingenuity Pathway Analysis(IPA)was conducted to screen and obtain key exosome-derived cartilage degeneration-related genes.Finally,qRT-PCR was used to verify the expression of key genes in osteoarthritis cartilage tissue and interleukin-1β stimulated chondrocyte models.RESULTS AND CONCLUSION:(1)There were 831 differentially expressed genes in the GSE185059 dataset and 5 323 differentially expressed genes in the GSE114007 dataset.A total of 94 exosome-derived cartilage degeneration related genes were screened after the intersection of these differentially expressed genes,of which 51 genes were down-regulated and 43 genes were up-regulated.(2)GO functional enrichment analysis showed that the up-regulated genes were mainly involved in the positive regulation of cell-cell adhesion,the positive regulation of T cell activation,and chronic inflammatory response,while the down-regulated genes were mainly involved in biological processes such as cell aggregation,cartilage differentiation and development,and skeletal system morphogenesis.(3)KEGG pathway enrichment analysis showed that exosome-derived cartilage degeneration-related genes were mainly involved in tryptophan enrichment metabolism,vitamin B6 metabolism,and leukocyte transendothelial migration.(4)The constructed protein-protein interaction network confirmed the existence of multiple interaction relationships among exosome-derived cartilage degeneration-related genes.Combined with five algorithms in CytoHubba software,four key exosome-derived cartilage degeneration-related genes were further screened,namely THY1,CYP1A1,NFKB2,and COL6A3.(5)The results of qRT-PCR showed that compared with normal cartilage,the expressions of THY1 and COL6A3 in osteoarthritic cartilage were increased,while the expression of CYP1A1 and NFKB2 was decreased.Similarly,compared with the unstimulated group,the expression of THY1 and COL6A3 in the interleukin-1β induced chondrocytes was upregulated,while the expression of CYP1A1 and NFKB2 was downregulated.(6)These results indicate that THY1,CYP1A1,NFKB2,and COL6A3 are genes related to cartilage degeneration in the exosomes of synovial fluid of patients with osteoarthritis,and may participate in the pathogenesis of osteoarthritis by regulating biological processes such as protein tyrosine kinase activity and lipid metabolism,as well as nuclear factor-κB signaling pathway and focal adhesion signaling pathway.However,the specific regulatory roles and molecular mechanisms of these key genes in cartilage degeneration need to be further verified by experiments.

Mechanical pain is one of the most common causes of clinical pain, but there remains a lack of effective treatment for debilitating mechanical and chronic forms of neuropathic pain. Recently, neurotoxin GsMTx4, a selective mechanosensitive (MS) channel inhibitor, has been found to be effective, while the underlying mechanism remains elusive. Here, with multiple rodent pain models, we demonstrated that a GsMTx4-based 17-residue peptide, which we call P10581, was able to reduce mechanical hyperalgesia and neuropathic pain. The analgesic effects of P10581 can be as strong as morphine but is not toxic in animal models. The anti-hyperalgesic effect of the peptide was resistant to naloxone (an μ-opioid receptor antagonist) and showed no side effects of morphine, including tolerance, motor impairment, and conditioned place preference. Pharmacological inhibition of TRPV4 by P10581 in a heterogeneous expression system, combined with the use of Trpv4 knockout mice indicates that TRPV4 channels may act as the potential target for the analgesic effect of P10581. Our study identified a potential drug for curing mechanical pain and exposed its mechanism.

Autism spectrum disorder(ASD) is a neurodevelopmental disorder, and social impairment was one of the core symptoms of ASD, which can seriously affects the social life of patients.The pathogenesis of social impairment in ASD is unclear and it may involves many brain abnormalities.The related theories and hypotheses are numerous and there is no unified conclusion. Studies have shown that the cerebellum has extensive connections with brain networks and is involved in the regulation of social cognition, but its role in ASD has not been fully emphasized.The structural and functional abnormalities of the cerebellar-cortex (CC) loop in ASD patients can lead to language communication disorders, empathy disorders, difficulties in interpreting social cues, abnormal social reward processing and emotional regulation disorders, which are closely related to ASD social impairment. Noninvasive brain stimulation of the superficial cerebellum can improve the abnormal CC circuit in ASD patients, and the cerebellum can be considered as a target for the treatment of social disorders in ASD in the future.Based on the clinical and basic researches on social impairment in ASD in recent years, this article reviews the relevant manifestations of disorders which cerebellar and CC circuit involved, aiming to promote the development of related research in the future.