Interferon stimulating factor STING, a transmembrane protein residing in the endoplasmic reticulum, is extensively involved in the sensing and transduction of intracellular signals and serves as a crucial component of the innate immune system. STING is capable of directly or indirectly responding to abnormal DNA originating from diverse sources within the cytoplasm, thereby fulfilling its classical antiviral and antitumor functions. Structurally, STING is composed of 4 transmembrane helices, a cytoplasmic ligand binding domain (LBD), and a C terminal tail structure (CTT). The transmembrane domain (TM), which is formed by the transmembrane helical structures, anchors STING to the endoplasmic reticulum, while the LBD is in charge of binding to cyclic dinucleotides (CDNs). The classical second messenger, cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), represents a key upstream molecule for STING activation. Once cGAMP binds to LBD, STING experiences conformational alterations, which subsequently lead to the recruitment of Tank-binding kinase 1 (TBK1) via the CTT domain. This, in turn, mediates interferon secretion and promotes the activation and migration of dendritic cells, T cells, and natural killer cells. Additionally, STING is able to activate nuclear factor-κB (NF-κB), thereby initiating the synthesis and release of inflammatory factors and augmenting the body’s immune response. In recent years, an increasing number of studies have disclosed the non-classical functions of STING. It has been found that STING plays a significant role in organelle regulation. STING is not only implicated in the quality control systems of organelles such as mitochondria and endoplasmic reticulum but also modulates the functions of these organelles. For instance, STING can influence key aspects of organelle quality control, including mitochondrial fission and fusion, mitophagy, and endoplasmic reticulum stress. This regulatory effect is not unidirectional; rather, it is subject to organelle feedback regulation, thereby forming a complex interaction network. STING also exerts a monitoring function on the nucleus and ribosomes, which further enhances the role of the cGAS-STING pathway in infection-related immunity. The interaction mechanism between STING and organelles is highly intricate, which, within a certain range, enhances the cells’ capacity to respond to external stimuli and survival pressure. However, once the balance of this interaction is disrupted, it may result in the occurrence and development of inflammatory diseases, such as aseptic inflammation and autoimmune diseases. Excessive activation or malfunction of STING may trigger an over-exuberant inflammatory response, which subsequently leads to tissue damage and pathological states. This review recapitulates the recent interactions between STING and diverse organelles, encompassing its multifarious functions in antiviral, antitumor, organelle regulation, and immune regulation. These investigations not only deepen the comprehension of molecular mechanisms underlying STING but also offer novel concepts for the exploration of human disease pathogenesis and the development of potential treatment strategies. In the future, with further probing into STING function and its regulatory mechanisms, it is anticipated to pioneer new approaches for the treatment of complex diseases such as inflammatory diseases and tumors.

In recent years, China has been facing the dual challenges of declining fertility rates and births, with male reproductive health issues, especially the decline in semen quality, identified as a pivotal contributor to this phenomenon. Meanwhile, accumulating evidence indicates that air pollutants, an increasingly severe environmental problem, can damage semen quality not only directly through their biological toxicity but also indirectly by disrupting the composition of microbial communities in the gut and semen, thereby dysregulating immune function, endocrine homeostasis, and oxidative stress responses. The gut microbiota and semen microbiota, as important components of the human microecosystem, play crucial roles in maintaining reproductive health. This article comprehensively reviewed the research progress on the potential effects of air pollutants (particulate matter and gaseous pollutants), gut microbiota, and semen microbiota on semen quality. Specifically, it elucidated the mechanisms of interaction between these factors and explored how they affect male fertility.

Aim To investigate the effect of ACSL4 on the malignant biological behavior of esophageal cancer cells and gefitinib resistance by regulating FASN,and to explore the related mechanism.Methods Thirty-five fresh esophageal cancer tissues and adjacent nor-mal tissues,and 30 esophageal cancer tissues with ge-fitinib resistance were collected.The expressions of ACSL4 and FASN were detected by qRT-PCR and im-munohistochemistry.The expression levels of ACSL4 and FASN in human normal esophageal cells HET-1 A,esophageal cancer cell lines ECA109,EC9706,TE-1 and TE-1/GR were detected by qRT-PCR.Cells in each group were constructed by liposome transfection technique,and the drug resistance and proliferation a-bility of cells were detected by cloning and CCK-8 as-say,cell apoptosis was detected by flow cytometry,cell invasion ability was detected by Transwell,and EMT pathway protein expression was detected by Western blot.Results Compared with adjacent normal tis-sues,the expression of ACSL4 and FASN genes in cancer tissues increased,and there was a positive corre-lation.The expression of ACSL4 significantly increased in ECA109,EC9706 and TE-1 cells compared with HET-1 A cells.With the increase of gefitinib concen-tration,the expression of ACSL4 in TE-1 cells gradually increased,and the expression of ACSL4 in TE-1/GR cells was higher than that of TE-1.Compared with the control group and the si-NC group,the cell proliferation and invasion ability of si-ACSL4 group decreased,the number of apoptosis increased,the expression of E-Cadherin increased,and the expression of N-Cadherin,Vimentin and β-catenin decreased.The response ex-periment showed that compared with the si-ACSL4 group and the si-ACSL4+oe-NC group,the cells in the si-ACSL4+oe-FASN group increased drug resistance,increased proliferation and invasion ability,decreased apoptosis number and decreased expression of E-Cad-herin.The expressions of N-Cadherin,Vimentin and β-catenin increased.Conclusions By down-regulating the expression of FASN,ACSL4 reverses the resistance of esophageal cancer TE-1/GR cells to gefitinib and in-hibits the proliferation,invasion and accelerates apopto-sis of TE-1/GR cells,which may be related to the regu-lation of EMT signaling pathway.

Aim To examine the pathogenesis of disul-fide death gene in vascular dementia(VD)by bioin-formatics analysis of disulfide death differentially ex-pressed genes(DEGs)combined with experimental verification.Methods The death DEGs of disulfide were screened and their correlation was analyzed.The VD patients data in the data set were analyzed by clus-tering and typing and gene set variation.The clustering risk of DEGs was tested with a nomogram model,and the optimal learning model was predicted.After the es-tablishment of VD rat model,water maze test,HE stai-ning and RT-qPCR detection were performed to verify the results of health information.Results Four DEGs including SLC7A11 were obtained,which had antago-nistic or synergistic interaction with each other.The genetic data could be divided into two subtypes with significant differences.After typing,VD disulfide DEGs were mainly concentrated in GnRH signaling pathways.The accuracy of the nomogram prediction model was high.Generalized linear was the best ma-chine learning model.Compared with the sham opera-tion group,the escape latency of rats in the model group was prolonged,the number of crossing platforms decreased,the relative mRNA expression levels of Slc3a2 and Slc7a11 decreased,and LRPPRC in-creased.Conclusions SLC7A11 and other disulfide death DEGs and its related GnRH signaling pathway may be an important part of the pathogenesis of VD di-sulfide death.SLC3A2,LRPPRC and SLC7A11 can be used as characteristic genes in the regulation of VD by disulfide death,which may affect VD progression through the regulation of disulfide death.

Aim To explore the effects of nuciferine on cognitive behavior and the underlying mechanisms,white matter injury(WMI),neuroinflammation,and ferroptosis in mice with chronic ischemic WMI.Meth-ods Sixty C57BL/6 mice were divided into a control group,a bilateral common carotid artery stenosis(BCAS)model group,and low/high-dose nuciferine groups(20/40 mg·kg-1).A chronic ischemic WMI model was established using BCAS surgery.Following eight weeks of treatment,cognitive behavior(Y-maze,novel object recognition,Morris water maze),white matter integrity(LFB/MBP staining),microglial acti-vation(Iba-1 immunofluorescence),inflammatory cy-tokines(ELISA for TNF-α,IL-1β,IL-6),ferroptosis markers(Fe2+,ROS,MDA,GSH),mitochondrial ultrastructure(electron microscopy),and protein ex-pression of the PI3K/Akt and NRF2/xCT/GPX4 signa-ling pathways(Western blot)were evaluated.Results Compared with the control group,the BCAS group showed significant cognitive decline(P＜0.05),re-duced myelin density,elevated inflammatory cytokines and ferroptosis markers(Fe2+,ROS,MDA),shrunk-en mitochondria,and downregulated PI3K/Akt and NRF2/xCT/GPX4 pathway proteins(P＜0.05).Nu-ciferine intervention significantly ameliorated these in-juries in BCAS mice,with the high-dose group exhibi-ting superior effects(P＜0.05).Conclusions Nu-ciferine exerts protective effects against chronic ische-mic WMI and cognitive impairment by activating the PI3K/Akt and NRF2/xCT/GPX4 signaling pathways,thereby suppressing neuroinflammation and ferroptosis.

Objective:To explore the effect of Lactobacillus reuteri on testicular injury in mice exposed to neonicotinoid insec-ticides(NNI).Methods:Fifteen C57BL/6 male mice were randomly divided into control group(CTRI.group),exposure group(NNI group)and Lactobacillus intervention group(NNI-L group).The mice in CTRL group were given 0.02ml/g of 0.5％carboxym-ethyl cellulose sodium solution by gavage for 14 days.The mice in NNI group were given 0.02 ml/g of NNI mixture by gavage for 14 days.The mice in NNI-L group were given 0.02 ml/g of NNI mixture by gavage and 5 × 108cfu/ml of Lactobacillus reuteri powder so-lution for 14 days.Then,the histomorphology and function of testicle were evaluated by hematoxylin-eosin staining,immunofluores-cence staining and RNA sequencing.Results:Compared with CTRL group,the thickness of testicular seminiferous epithelium in the NNI group was significantly thinner.And the decline in the number of spermatogenic cells and sperm was observed.And the expression of spermatogonial stem cell marker UCHL1 was down-regulated which was significantly improved in NNI-L group compared with the NNI group.The abnormal expressions of hormone and sperm methylation related genes in testis of NNI group were detected by RNA sequen-cing,with significant down-regulation being found in NPFF and IGF2.While the expression of HSD3B8 was significantly up-regulated.The abnormal expression of these genes could be significantly improved after oral administration of Lactobacillus reuteri.Conclusion:Testicular spermatogenesis and endocrine function can be damaged by NNI exposure.And oral administration of Lactoba-cillus reuteri protects testis from the adverse effects of NNI toxicity.

Aim To explore the roles and mechanisms of long non-coding RNA(lncRNA)AC087388.1 and poly(A)binding protein cytoplasmic 1(PABPC1)in esophageal squamous cell carcinoma(ESCC).Meth-ods The expression level of AC087388.1 in ESCC tissues and cells was detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)and fluorescence in situ hybridization experiments and its clinical relevance was analyzed.Cell counting kit-8(CCK-8),clone formation,scratch and Transwell inva-sion assays were used to detect the effects of knock-down of AC087388.1 on the cell viability,prolifera-tion,migratory,and invasion of ESCC cells respectively ability,and sub-localization in cells.RNA pull down and Western blot experiments were employed to verify the interaction between AC087388.1 and PABPC1 in ESCC cells.Salvage experiments were performed to detect the effect of AC087388.1 targeting PABPC1 on ESCC cells.Results AC087388.1 was highly ex-pressed in ESCC tissues and cells and positively corre-lated with clinical stage of ESCC patients,mainly local-ized in cytoplasm.Knockdown AC087388.1 inhibited ESCC cell viability,proliferation,migration and inva-sionability.PABPC1 was selected from the results of RNA Pull Down-MS experiments for subsequent experi-ments,and AC087388.1 was verified to bind to PAB-PC1 by RNA Pull Down and Western blot experiments.Overexpression of AC087388.1 was verified by rescue experiment to reverse the effects of knockdown of PAB-PC1 on ESCC cell viability,proliferation,migration and invasion.Conclusions High expression of AC087388.1 correlates with clinical stage and may be a risk factor for ESCC progression.AC087388.1 pro-motes the cell viability,proliferation,migration and in-vasive ability of ESCC cells by targeting PABPC1,which may be a novel biomarker for the diagnosis and treatment of ESCC.

Aim To investigate the effects of circ_0071653 targeting miR-197-3p on the proliferation and metastasis of esophageal squamous cell carcinoma(ES-CC)cells.Methods The circular structure of circ_0071653 was confirmed by Sanger sequencing and ribo-nuclease R tolerance experiments.Real-time quantita-tive polymerase chain reaction(RT-qPCR)and tissue fluorescence in situ hybridization assay were performed to detect the circ_0071653 expression levels and ana-lyze its clinical relevance.Cell fluorescence in situ hy-bridization and nuclear cytoplasmic separation assays were used to verify the subcellular localization of circ_0071653 and miR-197-3p.Bioinformatics analysis,dual luciferase reporter gene and RT-qPCR assays were conducted to validate the interactions between circ_0071653 and miR-197-3p.Moreover,the cell counting Kit-8(CCK-8),colony formation,scratch,Transwell invasion and subcutaneous tumor formation in nude mice assays were used to evaluate the effects of circ_0071653 and miR-197-3p on cell viability,prolifera-tion,migration,and invasion and in vivo tumorigenesi-sability.Results Circ_0071653 was a circular RNA,which showed high expression in ESCC cell lines and tissues.The expression of circ_0071653 was signifi-cantly correlated with lymph node metastasis and clini-cal stage of ESCC patients.Circ_0071653 and miR-197-3p were mainly localized in the cytoplasm.The databases predict that circ_0071653 had complementa-ry binding sites with miR-197-3p,and their binding were confirmed by dual luciferase reporter geneand RT-qPCR assays.Moreover,the activity,proliferation,migration,invasion and in vivo tumorigenesis abilities of ESCC cells were significantly reduced after knocking down circ_0071653,and this effect could be reversed by downregulating the expression of miR-197-3p.Con-clusions Circ_0071653 promotes the malignant pro-gression of ESCC through targeted regulation of miR-197-3p.

Objective To analyze the characteristics of spirometry and type 2 inflammation indicators of patients with CVA,ACO and CA to determine their clinical utility in identifying and distinguishing among CVA,ACO and CA patients.Methods Clinical data from 483 patients diagnosed with bronchial asthma,CVA,and bronchial asthma combined with chronic obstructive pulmonary disease in the outpatient department of the First Affiliated Hospital of Soochow University from July 2023 to June 2024 were collected and divided into CA,CVA and ACO groups according to diagnosis.Comparison of spirometry,fractional exhaled nitric oxide(FeNO),blood eosinophil(EOS),serum total immunoglobulin E(tIgE)and other tests between CA and CVA,CA and ACO groups.Perform logistic regression analysis on significant test results,then construct receiver operating characteristic(ROC)curves to compare the area under the curve and corresponding cut-off values.Result There was a statistically significant difference in tIgE between the CVA and CA groups(P=0.018),whereas no significant differences were observed in FeNO and EOS.Additionally,no notable differences were found between the ACO and CA groups in tIgE,FeNO,or EOS.Finally,FEV1％pred(OR=1.086,P=0.019),FEV1/FVC(OR=1.153,P=0.023),and MEF50％pred(OR=0.922,P=0.045)were used to construct the discriminative model between CA and CVA.ROC curves were plotted,with FEV1％pred showing an AUC of 0.680(P<0.001),a Youden index of 0.358,and a corresponding cutoff value of 89.200.FEV1/FVC had an AUC of 0.684(P<0.001),a Youden index of 0.334,and a cutoff value of 76.075.MEF50％pred had an AUC of 0.668(P<0.001),a Youden index of 0.309,and a cutoff value of 59.800.The combined sensitivity of these three measures was 0.909,specificity was 0.514,positive predictive value was 0.600,negative predictive value was 0.873,and the AUC was 0.773(P<0.001),with a Youden index of 0.423.FEV1(OR=0.002,P=0.045),FEV1％pred(OR=1.490,P=0.006),and FEV1/FVC(OR=0.749,P=0.005)were used to construct the discriminative model between CA and ACO.ROC curves were plotted,with FEV1 showing an AUC of 0.819(P<0.001),a Youden index of 0.532,and a corresponding cutoff value of 2.060.FEV1％pred had an AUC of 0.788(P<0.001),a Youden index of 0.501,and a cutoff value of 75.000.FEV1/FVC had an AUC of 0.891(P<0.001),a Youden index of 0.678,and a cutoff value of 68.620.The combined sensitivity of these three measures was 1.000,specificity was 0.904,positive predictive value was 0.771,negative predictive value was 1.000,and the AUC was 0.973(P<0.001),with a Youden index of 0.904.Conclusions Differences exist in the spirometry among CVA,ACO and CA.The spirometry results incor-porated into the discriminative models provide good discriminative value for distinguishing between CA and CVA patients with similar clinical symptoms,as well as for identifying ACO in the CA population.

The research investigated the characteristics of lymphocyte subsets in peripheral blood of children with mycoplasma pneumoniae pneumonia in different infection states. The retrospective cross-sectional study selected 194 children with pneumonia from October 2023 to January 2024 in Zhongnan Hospital of Wuhan University as the study objects, patients aged 7 months to 13 years old, including 91 female children and 103 male children. According to the types of pathogens, the children with pneumonia were divided into single MP infection group (80 cases), non-MP infection group (29 cases) and mixed pathogen infection group (85 cases). According to the mutation of MP23S rRNA gene, the MPP children were divided into drug-resistance group (112 cases) and non-drug-resistance group (53 cases). According to the results of bronchoscopy and imaging, the MPP children were divided into severe group (35 cases) and mild group (130 cases). Pathogen infection, the percentage and absolute count of lymphocyte subsets in peripheral blood, hypersensitive CRP, interferon-γ, tumor necrosis factor-α, interleukin-10, interleukin-4, interleukin-6 and interleukin-2 in each group were analyzed retrospectively. The levels of the test items in each group were compared. The value of peripheral blood lymphocyte subsets in the diagnosis of MPP in children was evaluated by ROC curve. The results showed that the co-infection rate of MPP children was 51.51% (85/165). Streptococcus pneumoniae was the most common co-infection (39/85, 45.88%), followed by Haemophilus influenzae (26/85, 30.89%). The mutation rate of MP resistance gene was 67.88% (112/165) in MPP children tested for tNGS in bronchoalveolar lavage fluid. The absolute counts (cells/μl) of CD3 +, CD3 +CD4 +, CD3 +CD8 +, CD3 -CD19 +, CD3 -CD16 +CD56 +and CD3 +CD16 +CD56 + in the simple MP group (1 164, 612, 415, 242, 168, 50) and the mixed pathogen group (1 285, 694, 457, 313, 176, 52) were significantly lower than those in the non-MP group (2 092, 1 037, 660, 541, 295, 86) ( P<0.05). There was no significant difference between drug-resistant group and non-drug-resistant group ( P>0.05). The CD3 +CD4 +% (34.91) and the absolute counts of CD3 -CD16 +CD56 + (148 cells/μl) in severe group was significantly lower than that in mild group (37.91, 187 cells/μl), and CD3 -CD19 +% (19.48) was significantly higher than that in mild group (16.33) ( P<0.05). The median values (cells/μl) of CD3 + (1 093, 925), CD3 +CD4 + (576, 543), CD3 +CD8 + (401, 356), CD3 -CD19 + (238, 234) and CD3 -CD16 +CD56 + (181, 153) in MPP children aged 4 to 8 years and 9 to 12 years were lower than the reference range in corresponding age. ROC curve analysis showed that the AUC of peripheral blood lymphocyte subsets for MPP diagnosis was 0.813, and the sensitivity was 79.3%, the specificity was 75%. In conclusion, the co-infection rate of MPP children was higher than single MP infection. The characteristics of peripheral blood lymphocyte subsets in children with pneumonia were that the absolute count test value of MPP children was significantly lower than that of non-MP infection, and there are differences between MPP children clinical types.