ObjectiveTo explore the function and related molecular mechanisms of magnoflorine against colon cancer via network pharmacology， molecular docking， and in vitro cell experiments. MethodsIn this study， the canonical SMILES of magnoflorine was obtained from the PubChem database， and the potential targets of magnoflorine were predicted by the Swiss Target Prediction database， while the disease targets of colon cancer were obtained from the DisGeNET， GeneCards and OMIM databases. The intersecting targets between magnoflorine's predicted targets and colon cancer disease targets were taken， and a protein-protein interaction （PPI） network was constructed and analyzed. The DAVID online database was employed to conduct Gene Ontology （GO） and KEGG pathway enrichment analyses on core targets. The top five key targets screened were docked with magnoflorine using AutoDock software. Finally， cellular experiments including CCK-8 assays， EdU experiments， cell scratch assays， and Transwell assays were conducted to validate the results from network pharmacology and molecular docking. Results44 key targets of magnoflorine in resisting colon cancer were acquired. The molecular docking results showed that magnoflorine had a strong binding activity with the core target signal transducer and activator of transcription 3 （STAT3） in the top five of the PPI network. Cellular experiments confirmed that magnoflorine could inhibit the proliferation and migration of colon cancer cells by suppressing the JAK/STAT3 signaling pathway. ConclusionMagnoflorine may inhibit the proliferation and migration of colon cancer cells by regulating the JAK/STAT3 signaling pathway.

Objective: This study aimed to systematically evaluate potential causal relationships between nine cathepsins and female infertility using Mendelian randomization (MR) methods. Methods: A bidirectional MR analysis was conducted utilizing single nucleotide polymorphisms as instrumental variables to investigate the potential causal effects between nine cathepsins and female infertility. Genetic data on female infertility were sourced from the FinnGen study, and cathepsin-related data were obtained from genome-wide association studies datasets of European ancestry. Results: Elevated levels of cathepsin E were significantly and inversely associated with the risk of female infertility, suggesting a potential protective role. This finding was further supported by multivariable MR analysis. However, no significant associations were observed between the other eight cathepsins and female infertility. Conclusion This study represents the first systematic MR analysis to identify a potential protective effect of cathepsin E on female infertility.

Objective: This study aimed to systematically evaluate potential causal relationships between nine cathepsins and female infertility using Mendelian randomization (MR) methods. Methods: A bidirectional MR analysis was conducted utilizing single nucleotide polymorphisms as instrumental variables to investigate the potential causal effects between nine cathepsins and female infertility. Genetic data on female infertility were sourced from the FinnGen study, and cathepsin-related data were obtained from genome-wide association studies datasets of European ancestry. Results: Elevated levels of cathepsin E were significantly and inversely associated with the risk of female infertility, suggesting a potential protective role. This finding was further supported by multivariable MR analysis. However, no significant associations were observed between the other eight cathepsins and female infertility. Conclusion This study represents the first systematic MR analysis to identify a potential protective effect of cathepsin E on female infertility.

Objective: This study aimed to systematically evaluate potential causal relationships between nine cathepsins and female infertility using Mendelian randomization (MR) methods. Methods: A bidirectional MR analysis was conducted utilizing single nucleotide polymorphisms as instrumental variables to investigate the potential causal effects between nine cathepsins and female infertility. Genetic data on female infertility were sourced from the FinnGen study, and cathepsin-related data were obtained from genome-wide association studies datasets of European ancestry. Results: Elevated levels of cathepsin E were significantly and inversely associated with the risk of female infertility, suggesting a potential protective role. This finding was further supported by multivariable MR analysis. However, no significant associations were observed between the other eight cathepsins and female infertility. Conclusion This study represents the first systematic MR analysis to identify a potential protective effect of cathepsin E on female infertility.

Objective: This study aimed to systematically evaluate potential causal relationships between nine cathepsins and female infertility using Mendelian randomization (MR) methods. Methods: A bidirectional MR analysis was conducted utilizing single nucleotide polymorphisms as instrumental variables to investigate the potential causal effects between nine cathepsins and female infertility. Genetic data on female infertility were sourced from the FinnGen study, and cathepsin-related data were obtained from genome-wide association studies datasets of European ancestry. Results: Elevated levels of cathepsin E were significantly and inversely associated with the risk of female infertility, suggesting a potential protective role. This finding was further supported by multivariable MR analysis. However, no significant associations were observed between the other eight cathepsins and female infertility. Conclusion This study represents the first systematic MR analysis to identify a potential protective effect of cathepsin E on female infertility.

Objective:To investigate the pulmonary function in patients with Parkinson's disease(PD)and the association between pulmonary function and motor symptoms.Methods:A total of 104 PD patients were included in the study,and a portable spirometer was used to assess pulmonary function.According to the results of pulmonary function,the patients were divided into ventilation dys-function group with 37 patients and non-ventilation dysfunction with 67 patients,and clinical data were compared between the two groups.Univariate and multivariate logistic regression analyses were used to investigate the factors associated with abnormal pulmonary function,and a Spearman correlation analysis was used to investigate the correlation between pulmonary function parameters and motor symptoms.Results:There were significant differences in the scores of bradykinesia and postural gait between the two groups(P<0.05),and the logistic regression analysis showed a positive correlation between pulmonary ventilation dysfunction and postural gait score(regression coefficient β=0.171,95%CI=1.015-1.386,P=0.032).There were significant differences between the patients with different stages of PD in the pulmonary function parameters of the percentage of forced vital capacity in predicted value(t=2.143,P=0.034),the percentage of forced expiratory volume in 1 second(t=2.118,P=0.037),the percentage of predicted peak expiratory flow(t=2.002,P=0.048),maximum expiratory pressure as a percentage of predicted value(t=2.412,P=0.018),and maximum inspiratory pressure as a percentage of predicted value(t=2.119,P=0.036).Conclusion:The pulmonary function parameters of PD patients are lower than expected values,and the incidence rate of pulmonary ventilation dysfunction is 35.58%,with the main manifestation of restrictive ventilatory dysfunction.There is a correlation between pulmonary function and motor symptoms in PD patients.

Objective: This study aimed to systematically evaluate potential causal relationships between nine cathepsins and female infertility using Mendelian randomization (MR) methods. Methods: A bidirectional MR analysis was conducted utilizing single nucleotide polymorphisms as instrumental variables to investigate the potential causal effects between nine cathepsins and female infertility. Genetic data on female infertility were sourced from the FinnGen study, and cathepsin-related data were obtained from genome-wide association studies datasets of European ancestry. Results: Elevated levels of cathepsin E were significantly and inversely associated with the risk of female infertility, suggesting a potential protective role. This finding was further supported by multivariable MR analysis. However, no significant associations were observed between the other eight cathepsins and female infertility. Conclusion This study represents the first systematic MR analysis to identify a potential protective effect of cathepsin E on female infertility.

Objective:To investigate influences of tetrandrine(Tet)on proliferation,apoptosis and immune escape of melanoma cells by regulating cyclic GMP-AMP synthase(cGAS)-stimulator of interferon gene(STING)signal pathway.Methods:MV3 cells were divided into NC group,Tet-L group(5 μmol/L),Tet-M group(10 μmol/L),Tet-H group(15 μmol/L),RU.521(cGAS inhibi-tor)group(1 μmol/L),Tet-H+RU.521 group(15 μmol/L+1 μmol/L).Proliferation of MV3 cells was detected by CCK-8 and plate cloning test;apoptosis of MV3 cells was detected by flow cytometry;Western blot was used to detect expressions of proliferating cell nuclear antigen(PCNA),Bcl-2-associated X protein(Bax),TGF-β,cGAS,STING proteins in MV3 cells.Cells in above groups were co-cultured with NK cells for 48 h through Transwell chamber,and named NC co-culture group,Tet-L co-culture group,Tet-M co-culture group,Tet-H co-culture group,RU.521 co-culture group,Tet-H+RU.521 co-culture group,respectively.ELISA was used to detect levels of IFN-γ and Granzyme B in supernatant of co-cultured cells;change of NK cell killing activity was detected.Results:Compared with NC group,A450,cloning rate,PCNA and TGF-β protein expressions of MV3 cells in Tet-L group,Tet-M group and Tet-H group were decreased,apoptosis rate,Bax,cGAS,STING protein expressions were increased,which was in a dose dependent man-ner,change trend of corresponding indexes in RU.521 group was contrary to the above(P<0.05);compared with NC co-culture group,levels of IFN-γ,Granzyme B and NK cell killing activity in supernatant of Tet-L co-culture group,Tet-M co-culture group and Tet-H co-culture group were increased,which was in a dose-dependent manner,change trend of corresponding indexes in RU.521 co-culture group was opposite to the above(P<0.05);RU.521 attenuated inhibition of high-dose Tet on MV3 cell proliferation,immune escape and its promotion on apoptosis.Conclusion:Tet may inhibit melanoma cell proliferation,immune escape and promote cell apoptosis by activating cGAS-STING signal pathway.

Objective:To investigate the application in evaluating the course and the clinical effects of serum cytokines interleukin (IL)-2, IL-4, IL-6, IL-10, IL-17, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) levels, as well as neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) in patients with brucellosis.Methods:Using case-control method, from February 2023 to March 2024, 274 confirmed brucellosis patients [divided into acute and chronic groups ( n = 165, 109) according to the course of the disease] and 70 healthy individuals (control group) were selected at Beidahuang Group General Hospital for serum cytokines detection using cytometric bead array (CBA) method. Blood routine test, serum agglutination test (SAT) and blood culture were performed at the same time, and NLR and PLR were calculated. Cytokine levels, NLR, and PLR were compared in patients with different disease duration, with or without complications, with different SAT titers [high ( > 1 ∶ 100) and low (≤1 ∶ 100)], and with different blood culture results, and the effects of each indicator on the course of brucellosis were analyzed by logistic regression. Results:The levels of IL-2, IL-6, IL-10, IL-17, TNF-α and IFN-γ in the acute group [ M ( Q1, Q3): 0.32 (0.15, 0.70), 18.97 (10.70, 36.86), 2.54 (1.49, 4.36), 1.41 (0.38, 3.05), 1.31 (0.77, 2.33), 11.60 (2.30, 36.75) ng/L] were higher than those in the chronic group [0.18 (0.06, 0.43), 1.68 (0.75, 5.74), 0.88 (0.40, 1.93), 0.29 (0.09, 0.87), 0.59 (0.31, 1.07), 0.72 (0.33, 1.42) ng/L] and control group [0.10 (0.05, 0.30), 1.52 (0.09, 2.80), 0.72 (0.35, 1.16), 0.08 (0.03, 0.20), 0.55 (0.20, 0.96), 0.68 (0.41, 1.25) ng/L, P < 0.05]. The IFN-γ level in the group with complications of brucellosis was lower than that in the group without complications, while the NLR and PLR were higher than those in the group without complications ( P < 0.05). The levels of IL-6, IL-17, TNF-α, and IFN-γ in the high titer group were higher than those in the low titer group, and the NLR was lower than that in the low titer group ( P < 0.05). The levels of IFN-γ and TNF-α of blood culture positive patients in the acute group were higher than those of blood culture negative patients ( P < 0.05). Univariate analysis showed that all 7 cytokines could affect the course of brucellosis ( P < 0.05). Multivariate analysis showed that IL-6, TNF-α, and IFN-γ were independent influencing factors of the course of brucellosis [ OR (95% CI) = 0.87 (0.83, 0.91), 0.55 (0.32, 0.97), 0.80 (0.72, 0.88), P < 0.05]. Conclusions:The levels of cytokines IL-2, IL-6, IL-10, IL-17, TNF-α, and IFN-γ can reflect the course progression of brucellosis patients, IL-6, IFN-γ and TNF-α can also serve as independent influencing factors for brucellosis progression. NLR and PLR may become inflammatory markers for predicting Brucella infection.

Approximately 300 million tons of plastic are produced globally each year,which has a serious impact on human health,marine life and the livestock industry.Microplastics have also been detected in meat and milk samples.Research has shown that nanoplastics(NP)(＜1 μm)and mi-croplastics(MP)(1 μm-5 mm)can affect the digestive,immune and reproductive systems of ani-mals.This experiment aims to investigate whether NP and MP regulate autophagy and damage the nervous system and spatial memory of animals.This experiment was divided into control group,nanoplastic group(PS-NP group,0.1 μm)and microplastic group(PS-MP group,1 μm),with 20 mice in each group.The mice were given 0.5 mL of PS-NP and PS-MP every day for 35 consecutive days,followed by neck amputation and brain analysis.The results showed that NPs and MPs of dif-ferent diameters caused varying degrees of damage to the brains of mice.In the behavioral tests of new object recognition,barnes maze and Y-shaped maze spatial memory,compared with the control group,the PS-NP group and PS-MP group showed a significant decrease in spatial memory ability of mice.HE staining results showed that neuronal cells in the PS-NP and PS-MP groups of mice exhibited shrinkage,decreased cell volume and deepened staining.The number of Nissl bodies de-creased,leading to dissolution and disappearance.RT-PCR and Western blot results showed that compared with the control group,the expression of glutamate receptors NR1,NR2A and NR2B in-creased in mice administered NP and MP orally,while the expression of autophagy related proteins Parkin,LC3B and Beclin1 was inhibited.In summary,this study suggests that nanoplastics and mi-croplastics stimulate glutamate receptors in mice by inhibiting the autophagy pathway,leading to impaired spatial memory.