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.

Objective To compare the biological characteristics of human embryonic lung cell line MU-L2, MU-L2 cell line transfected with SV40-LT(MU-SVL2) and the international established human embryonic lung cell line MRC-5, in order to apply MU-L2 cell line to biomedical research and vaccine production.Methods MU-L2, MU-SVL2 and MRC-5 cells were cultured in MEM medium containing 10% NBS, and passed according to the requirements of the Chinese Pharmacopoeia(Volume Ⅲ, 2020 edition). The growth characteristics of three kinds of cells were observed under microscope, CCK-8 assay was used to detect cell proliferation ability, qPCR was used to measure telomere relative length, soft agar clone formation test was used to analyze cell tumorigenicity, and Giemsa staining karyotype analysis was used to detect chromosome stability. The detection results of the cell lines were compared.Results After 72 h of culture, the three kinds of cells grew into a dense monolayer, and the cells showed a typical vortex-like arrangement, growing in good condition. The proliferation rates of MU-L2and MU-SVL2 cells were significantly higher than that of MRC-5 cells in 3-6 d of culture(F = 1. 893, P < 0. 05). With the increase of generations, the telomere relative length shortened accordingly, while the recent secondary telomere relative length values of MU-L2 and MU-SVL2 were higher than those of MRC-5 cells. No colony formation was found in the three kinds of cells, and they all belonged to normal diploid karyotype.Conclusion MU-L2 and MU-SVL2 cells have strong proliferation ability, better telomere stability, no tumorigenicity and stable chromosome, which are expected to be used in biomedical research and vaccine production.

Metabolic dysfunction-associated steatohepatitis (MASH), a severe type of metabolic dysfunction-associated steatotic liver disease (MASLD), is a leading etiology of end-stage liver disease worldwide, posing significant health and economic burdens. microRNA-320 (miR-320), a ubiquitously expressed and evolutionarily conserved miRNA, has been reported to regulate lipid metabolism; however, whether and how miR-320 affects MASH development remains unclear. By performing miR-320 in situ hybridization with RNAscope, we observed a notable downregulation of miR-320 in hepatocytes during MASH, correlating with disease severity. Most importantly, miR-320 downregulation in hepatocytes exacerbated MASH progression as demonstrated that hepatocyte-specific miR-320 deficient mice were more susceptible to high-fat, high-fructose, high-cholesterol diet (HFHC) or choline-deficient, amino acid-defined, high-fat diet (CDAHFD)-induced MASH compared with control littermates. Conversely, restoration of miR-320 in hepatocytes ameliorated MASH-related steatosis and fibrosis by injection of adeno-associated virus 8 (AAV8) carrying miR-320 in different types of diet-induced MASH models. Mechanistic studies revealed that miR-320 specifically regulated fibroblast growth factor 1 (FGF1) production in hepatocytes by inhibiting regulator factor X1 (RFX1) expression. Notably, knockdown of Rfx1 in hepatocytes mitigated MASH by enhancing FGF1-mediated AMPK activation. Our findings underscore the therapeutic potential of hepatic miR-320 supplementation in MASH treatment by inhibiting RFX1-mediated FGF1 suppression.

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.

This research study focuses on addressing the limitations of current neuropathic pain (NP) treatments by developing a novel dual-target modulator, E0199, targeting both Na_V1.7, Na_V1.8, and Na_V1.9 and K_V7 channels, a crucial regulator in controlling NP symptoms. The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP. Through an experimental design involving both in vitro and in vivo methods, E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury (CCI) mouse model. The results demonstrated that E0199 significantly inhibited Na_V1.7, Na_V1.8, and Na_V1.9 channels with a particularly low half maximal inhibitory concentration (IC₅₀) for Na_V1.9 by promoting sodium channel inactivation, and also effectively increased K_V7.2/7.3, K_V7.2, and K_V7.5 channels, excluding K_V7.1 by promoting potassium channel activation. This dual action significantly reduced the excitability of dorsal root ganglion neurons and alleviated pain hypersensitivity in mice at low doses, indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically. The safety of E0199 was supported by neurobehavioral evaluations. Conclusively, E0199 represents a ground-breaking approach in NP treatment, showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe therapeutic option for NP. This study introduces a promising direction for the future development of NP therapeutics.

The global outbreak of monkeypox in 2022 has aroused widespread concern in public health. To date, the prevention and treatment of monkeypox has mainly relied on smallpox vaccines and drugs. This study aims to screen and obtain therapeutic antibodies with high affinity, neutralizing activity, and protective effects, and provide candidate molecules for the development of specific therapeutic antibodies against monkeypox. Therefore, humanized mice were immunized to screen for antibodies against the envelope protein of the mpox virus. Two M1R-specific antibodies, 12G5 and 12H6, were obtained, with the affinity of 0.095 nmol/L and 0.089 nmol/L, respectively. The 50% reduction of the plaque counts (PRNT₅₀) of 12G5 and 12H6 was (1.821±1.766) μg/mL and (17.605±2.383) μg/mL, respectively. The two antibodies targeted two binding epitopes of M1R. Moreover, 12H6 could protect 60% of mice from death following the vaccinia virus challenge. This study provides research materials for subsequent in-depth studies on the immunoprotection of mpox virus and potential therapeutic strategies.
Animals ; Mice ; Antibodies, Viral/immunology* ; Monkeypox virus/immunology* ; Mpox, Monkeypox/immunology* ; Antibodies, Neutralizing/immunology* ; Viral Envelope Proteins/immunology* ; Humans ; Antibodies, Monoclonal/biosynthesis* ; Female

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.

BACKGROUND:Olfactory dysfunction is an early biological marker of various diseases.However,the neuroimaging mechanism by which olfactory dysfunction occurs following cerebral small vessel disease is unclear. OBJECTIVE:To explore the different neuroimaging mechanisms of olfactory function regulation in patients with cerebral small vessel disease and Parkinson's disease,and explore the potential application value of olfactory function assessment in patients with cerebral small vessel disease. METHODS:Neuropsychological and olfactory tests,high-resolution structural magnetic resonance and resting-state functional magnetic resonance data were collected in 80 patients with cerebral small vessel disease,44 healthy controls and 29 patients with Parkinson's disease.DPABI,SPM12 and SPSS were used to analyze and compare the amplitude of low frequency fluctuation,regional homogeneity and functional connectivity values between the cerebral small vessel disease,control and Parkinson's disease groups.Correlations between the significantly altered resting-state functional magnetic resonance imaging measures and olfactory and cognitive scores were evaluated. RESULTS AND CONCLUSION:Compared with the control group,low-frequency fluctuation amplitude of the right dorsolateral superior frontal gyrus and the regional homogeneity of the left wedge leaf were significantly reduced in the cerebral small vessel disease and Parkinson's disease groups.The right dorsolateral superior frontal gyrus and the left cuneiform lobe are the seed points.Compared with the Parkinson's disease group,the functional connectivity values of the right anterior cunei,inferior temporal gyrus,anterior central gyrus and dorsolateral superior frontal gyrus,left posterior central gyrus and inferior temporal gyrus were significantly enhanced in the control and cerebral small vessel disease groups.The left cuneiform lobe was the seed point.Compared with the control group,the functional connectivity of the left lingual gyrus was significantly weakened in the cerebral small vessel disease and Parkinson's disease groups.The functional connectivity values of the left middle temporal gyrus and the right posterior central gyrus were enhanced in the control group compared with the cerebral small vessel disease and Parkinson's disease group,and that was enhanced in the cerebral small vessel disease group compared with the Parkinson's disease group.Correlation analysis showed that the olfactory score and cognitive score were positively correlated in the cerebral small vessel disease group,and the regional homogeneity of the left wedge lobe was negatively correlated with the Montreal Cognitive Assessment Scale score,while the functional connectivity of left wedge lobe-left middle temporal gyrus in the Parkinson's disease group was positively correlated with the olfactory recognition score,and the functional connectivity values of the left wedge lobe-left posterior central gyrus and left wedge lobe-left lingual gyrus were positively correlated with the olfactory identification score and the total olfactory score,respectively.The regulation of olfactory function in patients with cerebral small vessel disease has a different neuroimaging mechanism from that of olfactory dysfunction in patients with Parkinson's disease.The olfactory function of patients with cerebral small vessel disease is related to cognitive function.It is speculated that the olfactory function following cerebral small vessel disease is a secondary change of brain dysfunction,while olfactory dysfunction following Parkinson's disease is directly caused by abnormal function of olfactory-related brain areas.Olfactory function assessment in patients with cerebral small vessel disease has potential application in predicting cognitive function.

Objective To investigate the effect of autophagy activation on cell proliferation in human umbilical vein endothelial cells(HUVECs).Methods HUVECs were treated with rapamycin(Rapa).Western blot assay was performed to examine the expression of protein of microtubule associated protein 1 light chain 3(LC3),Beclin 1 and unc-51-like kinase 1(ULK1).Autophagosomes were detected by transmission electron microscopy(TEM),and autophagy fluorescence was detected by monodansylcadaverine staining(MDC)assay.The effect of autophagy activation on cell proliferation was assessed by CCK-8 assay and EdU assay.Vascular formation experiments were used to detect vasculogenic ability.Results After Rapa treatment,LC3,Beclin1 and ULK1 expressions were en-hanced,while the green autophagy fluorescence expression in the experimental group was stronger than that in the control group,and autophagosomes were visible by TEM;CCK-8 and EdU results showed that compared with the control group,the cell proliferation ability was weakened and tubes formation ability was reduced after the activation of autophagy in experimental cells.Conclusion Rapa upregulates autophagy activity in HUVECs to inhibit cell proliferation under certain time.