FASN regulates STING palmitoylation via malonyl-CoA in macrophages to alleviate sepsis-induced liver injury.

STING (stimulator of interferon genes) is a critical immunoregulatory protein in sepsis and is regulated by various mechanisms, especially palmitoylation. FASN (fatty acid synthase) is the rate-limiting enzyme to generate cellular palmitic acid (PA) via acetyl-CoA and malonyl-CoA and participates in protein palmitoylation. However, the mechanisms underlying the interaction between STING and FASN have not been completely understood. In this study, STING-knockout mice were used to confirm the pivotal role of STING in sepsis-induced liver injury. Metabolomics confirmed the dyslipidemia in septic mice and patients. The compounds library was screened, revealing that FASN inhibitors exerted a significant inhibitory effect on the STING pathway. Mechanically, the regulatory effect of FASN on the STING pathway was dependent on palmitoylation. Further experiments indicated that the upstream of FASN, malonyl-CoA inhibited STING pathway possibly due to C91 (palmitoylated residue) of STING. Overall, this study reveals a novel paradigm of STING regulation and provides a new perspective on immunity and metabolism.

The Role of Gut Microbiota in Male Erectile Dysfunction of Rats.

PURPOSE: Erectile dysfunction (ED) is a common male sexual dysfunction. Gut microbiota plays an important role in various diseases. To investigate the effects and mechanisms of intestinal flora dysregulation induced by high-fat diet (HFD) on erectile function. MATERIALS AND METHODS: Male Sprague-Dawley rats aged 8 weeks were randomly divided into the normal diet (ND) and HFD groups. After 24 weeks, a measurement of erectile function was performed. We performed 16S rRNA sequencing of stool samples. Then, we established fecal microbiota transplantation (FMT) rat models by transplanting fecal microbiota from rats of ND group and HFD group to two new groups of rats respectively. After 24 weeks, erectile function of the rats was evaluated and 16S rRNA sequencing was performed, and serum samples were collected for the untargeted metabolomics detection. RESULTS: The erectile function of rats and the species diversity of intestinal microbiota in the HFD group was significantly lower, and the characteristics of the intestinal microbiota community structure were also significantly different between the two groups. The erectile function of rats in the HFD-FMT group was significantly lower than that of rats in the ND-FMT group. The characteristics of the intestinal microbiota community structure were significantly different. In the HFD-FMT group, 27 metabolites were significantly different and they were mainly involved in the several inflammation-related pathways. CONCLUSIONS: Intestinal microbiota disorders induced by HFD can damage the intestinal barrier of rats, change the serum metabolic profile, induce low-grade inflammation and apoptosis in the corpus cavernosum of the penis, and lead to ED.

FSformer: A combined frequency separation network and transformer for LDCT denoising.

Low-dose computed tomography (LDCT) has been widely concerned in the field of medical imaging because of its low radiation hazard to humans. However, under low-dose radiation scenarios, a large amount of noise/artifacts are present in the reconstructed image, which reduces the clarity of the image and is not conducive to diagnosis. To improve the LDCT image quality, we proposed a combined frequency separation network and Transformer (FSformer) for LDCT denoising. Firstly, FSformer decomposes the LDCT images into low-frequency images and multi-layer high-frequency images by frequency separation blocks. Then, the low-frequency components are fused with the high-frequency components of different layers to remove the noise in the high-frequency components with the help of the potential texture of low-frequency parts. Next, the estimated noise images can be obtained by using Transformer stage in the frequency aggregation denoising block. Finally, they are fed into the reconstruction prediction block to obtain improved quality images. In addition, a compound loss function with frequency loss and Charbonnier loss is used to guide the training of the network. The performance of FSformer has been validated and evaluated on AAPM Mayo dataset, real Piglet dataset and clinical dataset. Compared with previous representative models in different architectures, FSformer achieves the optimal metrics with PSNR of 33.7714 dB and SSIM of 0.9254 on Mayo dataset, the testing time is 1.825 s. The experimental results show that FSformer is a state-of-the-art (SOTA) model with noise/artifact suppression and texture/organization preservation. Moreover, the model has certain robustness and can effectively improve LDCT image quality.

Exploring the role of the LkABCG36 transporter in lignin accumulation.

Lignin is a complex biopolymer formed through the condensation of three monomeric precursors known as monolignols. However, the mechanism underlying lignin precursor transport remains elusive, with uncertainty over whether it occurs through passive diffusion or an active energized process. ATP-binding cassette 36 (ABCG36) plays important roles in abiotic stress resistance. In this study, we investigated the transport functions of LkABCG36 (Larix kaempferi) for lignin precursors and the potential effects of LkABCG36 overexpression in plants. LkABCG36 enhanced the ability of tobacco (Nicotiana tabacum) bright yellow-2 (BY-2) cells to resist monolignol alcohol stress. Furthermore, LkABCG36 overexpression promoted lignin deposition in tobacco plant stem tissue. To understand the underlying mechanism, we measured the BY-2 cell ability to export lignin monomers and the uptake of monolignol precursors in inside-out (inverted) plasma membrane vesicles. We found that the transport of coniferyl and sinapyl alcohols is an ATP-dependent process. Our data suggest that LkABCG36 contributes to lignin accumulation in tobacco stem tissues through a mechanism involving the active transport of lignin precursors to the cell wall. These findings shed light on the lignin biosynthesis process, with important implications for enhancing lignin deposition in plants, potentially leading to improved stress tolerance and biomass production.

Gastroesophageal reflux disease with 6 neurodegenerative and psychiatric disorders: Genetic correlations, causality, and potential molecular mechanisms.

The comorbidities between gastroesophageal reflux disease (GERD) and various neurodegenerative and psychiatric disorders have been widely reported. However, the genetic correlations, causal relationships, and underlying mechanisms linking GERD to these disorders remain largely unknown. Here, we conducted a bidirectional Mendelian randomization (MR) analysis to determine the causality between GERD and 6 neurodegenerative and psychiatric disorders. Sensitivity analyses and multivariable MR were performed to test the robustness of our findings. Linkage disequilibrium score regression was used to assess the genetic correlation between these diseases as affected by heredity. Multiple bioinformatics tools combining two machine learning algorithms were applied to further investigate the potential mechanisms underlying these diseases. We found that genetically predicted GERD significantly increased the risk of Alzheimer's disease, major depressive disorder, and anxiety disorders. There might be a bidirectional relationship between GERD and insomnia. GERD has varying degrees of genetic correlations with AD, ALS, anxiety disorders, insomnia, and depressive disorder. Bioinformatics analyses revealed the hub shared genes and the common pathways between GERD and 6 neurodegenerative and psychiatric disorders. Our findings demonstrated the complex nature of the genetic architecture across these diseases and clarified their causality, highlighting that treatments for the cure or remission of GERD may serve as potential strategies for preventing and managing neurodegenerative and psychiatric disorders.

Characteristics of Gut Microbiota in Patients with Erectile Dysfunction: A Chinese Pilot Study.

PURPOSE: Little is known about the role of gut microbiota in the pathogenesis of erectile dysfunction (ED). We performed a study to compare taxonomic profiles of gut microbiota of ED and healthy males. MATERIALS AND METHODS: A total of 43 ED patients and 16 healthy controls were enrolled in the study. The 5-item version of the International Index of Erectile Function (IIEF-5) with a cutoff value of 21 was used to evaluate erectile function. All participants underwent nocturnal penile tumescence and rigidity test. Samples of stool were sequenced to determine the gut microbiota. RESULTS: We identified a distinct beta diversity of gut microbiome in ED patients by unweighted UniFrac analysis (R²=0.026, p=0.036). Linear discriminant analysis effect size (LEfse) analysis showed Actinomyces was significantly enriched, whereas Coprococcus_1, Lachnospiraceae_FCS020_group, Lactococcus, Ruminiclostridium_5, and Ruminococcaceae_UCG_002 were depleted in ED patients. Actinomyces showed a significant negative correlation with the duration of qualified erection, average maximum rigidity of tip, average maximum rigidity of base, tip tumescence activated unit (TAU), and base TAU. Coprococcus_1, Lachnospiraceae_FCS020_group, Ruminiclostridium_5, and Ruminococcaceae_UCG_002 were significantly correlated with the IIEF-5 score. Ruminiclostridium_5 and Ruminococcaceae_UCG_002 were positively related with average maximum rigidity of tip, average maximum rigidity of base, ΔTumescence of tip, and Tip TAU. Further, a random forest classifier based on the relative abundance of taxa showed good diagnostic efficacy with an area under curve of 0.72. CONCLUSIONS: This pilot study identified evident alterations in the gut microbiome composition of ED patients and found Actinomyces was negatively correlated with erectile function, which may be a key pathogenic bacteria.

Identifying the Interaction Between Tuberculosis and SARS-CoV-2 Infections via Bioinformatics Analysis and Machine Learning.

The number of patients with COVID-19 caused by severe acute respiratory syndrome coronavirus 2 is still increasing. In the case of COVID-19 and tuberculosis (TB), the presence of one disease affects the infectious status of the other. Meanwhile, coinfection may result in complications that make treatment more difficult. However, the molecular mechanisms underpinning the interaction between TB and COVID-19 are unclear. Accordingly, transcriptome analysis was used to detect the shared pathways and molecular biomarkers in TB and COVID-19, allowing us to determine the complex relationship between COVID-19 and TB. Two RNA-seq datasets (GSE114192 and GSE163151) from the Gene Expression Omnibus were used to find concerted differentially expressed genes (DEGs) between TB and COVID-19 to identify the common pathogenic mechanisms. A total of 124 common DEGs were detected and used to find shared pathways and drug targets. Several enterprising bioinformatics tools were applied to perform pathway analysis, enrichment analysis and networks analysis. Protein-protein interaction analysis and machine learning was used to identify hub genes (GAS6, OAS3 and PDCD1LG2) and datasets GSE171110, GSE54992 and GSE79362 were used for verification. The mechanism of protein-drug interactions may have reference value in the treatment of coinfection of COVID-19 and TB.

Itaconate inhibits SYK through alkylation and suppresses inflammation against hvKP induced intestinal dysbiosis.

Hypervirulent Klebsiella pneumoniae (hvKP) is a highly lethal opportunistic pathogen that elicits more severe inflammatory responses compared to classical Klebsiella pneumoniae (cKP). In this study, we investigated the interaction between hvKP infection and the anti-inflammatory immune response gene 1 (IRG1)-itaconate axis. Firstly, we demonstrated the activation of the IRG1-itaconate axis induced by hvKP, with a dependency on SYK signaling rather than STING. Importantly, we discovered that exogenous supplementation of itaconate effectively inhibited excessive inflammation by directly inhibiting SYK kinase at the 593 site through alkylation. Furthermore, our study revealed that itaconate effectively suppressed the classical activation phenotype (M1 phenotype) and macrophage cell death induced by hvKP. In vivo experiments demonstrated that itaconate administration mitigated hvKP-induced disturbances in intestinal immunopathology and homeostasis, including the restoration of intestinal barrier integrity and alleviation of dysbiosis in the gut microbiota, ultimately preventing fatal injury. Overall, our study expands the current understanding of the IRG1-itaconate axis in hvKP infection, providing a promising foundation for the development of innovative therapeutic strategies utilizing itaconate for the treatment of hvKP infections.

Precise Orchestration of Gasdermins' Pore-Forming Function by Posttranslational Modifications in Health and Disease.

Gasdermins (GSDMs) serve as pivotal executors of pyroptosis and play crucial roles in host defence, cytokine secretion, innate immunity, and cancer. However, excessive or inappropriate GSDMs activation is invariably accompanied by exaggerated inflammation and results in tissue damage. In contrast, deficient or impaired activation of GSDMs often fails to promptly eliminate pathogens, leading to the increasing severity of infections. The activity of GSDMs requires meticulous regulation. The dynamic modulation of GSDMs involves many aspects, including autoinhibitory structures, proteolytic cleavage, lipid binding and membrane translocation (oligomerization and pre-pore formation), oligomerization (pore formation) and pore removal for membrane repair. As the most comprehensive and efficient regulatory pathway, posttranslational modifications (PTMs) are widely implicated in the regulation of these aspects. In this comprehensive review, we delve into the complex mechanisms through which a variety of proteases cleave GSDMs to enhance or hinder their function. Moreover, we summarize the intricate regulatory mechanisms of PTMs that govern GSDMs-induced pyroptosis.

4-octyl itaconate as a metabolite derivative inhibits inflammation via alkylation of STING.

The Krebs cycle-derived metabolite itaconate, whose production is catalyzed by immune response gene 1 (IRG1), has potential to link immunity and metabolism in activated macrophages through alkylation or competitive inhibition of target proteins. In support of this, our previous study demonstrated that the stimulator of interferon genes (STING) signaling platform functions as a hub in macrophage immunity and has a profound impact on the prognosis of sepsis. Interestingly, we find that itaconate, an endogenous immunomodulator, can significantly inhibit the activation of STING signaling. Moreover, 4-octyl itaconate (4-OI), which is a permeable itaconate derivative, can alkylate cysteine sites 65, 71, 88, and 147 of STING, thereby inhibiting its phosphorylation. Furthermore, itaconate and 4-OI inhibit the production of inflammatory factors in sepsis models. Our results broaden the knowledge on the role of the IRG1-itaconate axis in immunomodulation and highlight itaconate and its derivatives as potential therapeutic agents in sepsis.

Multi-Scale Feature Fusion Network for Low-Dose CT Denoising.

Computed tomography (CT) is an imaging technique extensively used in medical treatment, but too much radiation dose in a CT scan will cause harm to the human body. Decreasing the dose of radiation will result in increased noise and artifacts in the reconstructed image, blurring the internal tissue and edge details. To get high-quality CT images, we present a multi-scale feature fusion network (MSFLNet) for low-dose CT (LDCT) denoising. In our MSFLNet, we combined multiple feature extraction modules, effective noise reduction modules, and fusion modules constructed using the attention mechanism to construct a horizontally connected multi-scale structure as the overall architecture of the network, which is used to construct different levels of feature maps at all scales. We innovatively define a composite loss function composed of pixel-level loss based on MS-SSIM-L1 and edge-based edge loss for LDCT denoising. In short, our approach learns a rich set of features that combine contextual information from multiple scales while maintaining the spatial details of denoised CT images. Our laboratory results indicate that compared with the existing methods, the peak signal-to-noise ratio (PSNR) value of CT images of the AAPM dataset processed by the new model is 33.6490, and the structural similarity (SSIM) value is 0.9174, which also achieves good results on the Piglet dataset with different doses. The results also show that the method removes noise and artifacts while effectively preserving CT images' architecture and grain information.

Low-dose CT noise reduction based on local total variation and improved wavelet residual CNN.

BACKGROUND: Low-dose computed tomography (LDCT) is an effective method for reducing radiation exposure. However, reducing radiation dose leads to considerable noise in the reconstructed image that can affect doctor's judgment. OBJECTIVE: To solve this problem, this study proposes a local total variation and improved wavelet residual convolutional neural network (LTV-WRCNN) denoising model. METHODS: The model first introduces local total variation (LTV) to decompose the LDCT image into cartoon and texture image. Next, the texture image is filtered using the non-local mean (NLM). Then, the cartoon image is added to the filtered texture image to obtain the preprocessing image. Finally, the pre-processed image is fed into the improved wavelet residual neural network (WRCNN) to obtain an improved image. Additionally, we also introduce a compound loss in wavelet domain that combines mean squared error loss and directional regularization loss to separate the structural details from noise more thoroughly. RESULTS: Compared with state-of-the-art methods, the peak-signal-to-noise ratio (PSNR) value and the structure similarity (SSIM) value of the processed CT images using the new proposed model are 33.4229 dB and 0.9158. Study also shows that applying new model obtains better results visually and numerically, especially in terms of the preservation of structural details. CONCLUSIONS: The proposed new model is feasible and effective in improving the quality of LDCT images.

Sulfonated polybenzothiazole cathode materials for Na-ion batteries.

A new flexible aromatic polymer sulfonated polybenzothiazole (sPBT-SE) with sulphone and ether units is reported as an advanced cathode material for storing Na+, which delivers a high discharge capacity of 103 mA h g-1 after 350 cycles at 30 mA g-1.

Edge feature extraction-based dual CNN for LDCT denoising.

In low-dose computed tomography (LDCT) denoising tasks, it is often difficult to balance edge/detail preservation and noise/artifact reduction. To solve this problem, we propose a dual convolutional neural network (CNN) based on edge feature extraction (Ed-DuCNN) for LDCT. Ed-DuCNN consists of two branches. One branch is the edge feature extraction subnet (Edge_Net) that can fully extract the edge details in the image. The other branch is the feature fusion subnet (Fusion_Net) that introduces an attention mechanism to fuse edge features and noisy image features. Specifically, first, shallow edge-specific detail features are extracted by trainable Sobel convolutional blocks and then are integrated into Edge_Net together with the LDCT images to obtain deep edge detail features. Finally, the input image, shallow edge detail, and deep edge detail features are fused in Fusion_Net to generate the final denoised image. The experimental results show that the proposed Ed-DuCNN can achieve competitive performance in terms of quantitative metrics and visual perceptual quality compared with that of state-of-the-art methods.

Highly Active and Stable Large Mo-Doped Pt-Ni Octahedral Catalysts for ORR: Synthesis, Post-treatments, and Electrochemical Performance and Stability.

Over the past decade, advances in the colloidal syntheses of octahedral-shaped Pt-Ni alloy nanocatalysts for use in fuel cell cathodes have raised our atomic-scale control of particle morphology and surface composition, which, in turn, helped raise their catalytic activity far above that of benchmark Pt catalysts. Future fuel cell deployment in heavy-duty vehicles caused the scientific priorities to shift from alloy particle activity to stability. Larger particles generally offer enhanced thermodynamic stability, yet synthetic approaches toward larger octahedral Pt-Ni alloy nanoparticles have remained elusive. In this study, we show how a simple manipulation of solvothermal synthesis reaction kinetics involving depressurization of the gas phase at different stages of the reaction allows tuning the size of the resulting octahedral nanocatalysts to previously unachieved scales. We then link the underlying mechanism of our approach to the classical "LaMer" model of nucleation and growth. We focus on large, annealed Mo-doped Pt-Ni octahedra and investigate their synthesis, post-synthesis treatments, and elemental distribution using advanced electron microscopy. We evaluate the electrocatalytic ORR performance and stability and succeed to obtain a deeper understanding of the enhanced stability of a new class of relatively large, active, and long-lived Mo-doped Pt-Ni octahedral catalysts for the cathode of PEMFCs.

The Safety of Continuing Low-dose Aspirin Therapy Perioperatively in the Patients had Undergone Percutaneous Nephrolithotomy: A Systematic Review and Meta-analysis.

PURPOSE: Aspirin (ASA) is often stopped prior to percutaneous nephrolithotomy (PCNL) due to the surgical bleeding risk. However, this practice is based on expert opinion only, and mounting evidence suggests holding aspirin perioperatively can be more harmful than once thought. In our review we aimed to discuss the safety of low dose aspirin continued or discontinued in the whole perioperative period of PCNL. PATIENTS AND METHOD: We performed a computerized PubMed, EMBASE and Cochrane Library search of relevant studies. Study identification satisfied the PRISMA guidelines. Newcastle-Ottawa scale (NOS) was used to evaluate the quality of including studies. Favored outcomes such as operative time, complications and change in hemoglobin were extracted. Statistical analysis was performed with Rev-Man software 5.3 and forest plots were used to illustrate our findings. RESULTS: After screening, four studies were included in the present systematic review. There was no difference in the number of total complications (OR:1.25; 95 % CI 0.82-1.90; p=0.30), major complications (OR: 1.24; 95 % CI 0.53-2.93; p=0.62) and blood transfusion rate (OR:0.99; 95 % CI 0.46-2.12; p=0.98) between the continuing low dose aspirin group and discontinuing group. Moreover, the overall stone-free rate was also not statistically significant (OR:3.17; 95 % CI 0.89-11.25; p=0.07). It was similar about the change in hemoglobin, hematocrit and creatinine levels between two groups. CONCLUSION: Based on our findings, transient cessation of aspirin perioperatively seems not to be necessary for patients who need PCNL complicated with the necessity of aspirin therapy. However, further well-designed prospective studies with large sample size are needed to confirm and validate our findings.

Post-Translational Modifications of STING: A Potential Therapeutic Target.

Stimulator of interferon genes (STING) is an endoplasmic-reticulum resident protein, playing essential roles in immune responses against microbial infections. However, over-activation of STING is accompanied by excessive inflammation and results in various diseases, including autoinflammatory diseases and cancers. Therefore, precise regulation of STING activities is critical for adequate immune protection while limiting abnormal tissue damage. Numerous mechanisms regulate STING to maintain homeostasis, including protein-protein interaction and molecular modification. Among these, post-translational modifications (PTMs) are key to accurately orchestrating the activation and degradation of STING by temporarily changing the structure of STING. In this review, we focus on the emerging roles of PTMs that regulate activation and inhibition of STING, and provide insights into the roles of the PTMs of STING in disease pathogenesis and as potential targeted therapy.

Association between generalized anxiety symptoms and semen quality in infertile men: A multicentre study in North China.

This study was conducted to investigate the generalized anxiety levels and its association with semen quality in infertile men. We recruited male patients who visited the infertility outpatient departments of three teaching hospitals in North China and evaluated their generalized anxiety symptoms using the self-administered 7-item generalized anxiety disorder (GAD-7) scale. Seminal analysis was performed as per WHO guidelines. A total of 378 infertile men (average age: 31.43 ± 5.85 years) were classified into the normal group (n = 174, 46%) and the anxiety group (n = 204, 54%) according to their GAD-7 scale score. The proportion of patients with hyperlipidaemia in the normal group was significantly higher than that in the anxiety group (14.9% vs. 5.9%, p = 0.004). The other demographic characteristics were not statistically different between both groups. Patients with abnormal GAD-7 scale scores had a significantly lower sperm count (202.48 vs. 166.80 million per ejaculate, p = 0.023), sperm concentration (54.75 vs. 46.54 million/ml, p = 0.033), and progressive motility (40.25 vs. 37.16, p = 0.020) than those with normal GAD-7 scale scores. Multivariate linear regression models revealed that anxiety was significantly negatively associated with sperm concentration (percent change = -9.79, 95%CI: -12.38 to -7.12, p < 0.001), total sperm count (percent change = -13.07, 95%CI: -16.05 to -9.84, p < 0.001), progressive motility (ß = -1.41, 95%CI: -1.86 to -0.96, p < 0.001), total sperm motility (ß = -1.73, 95%CI: -2.38 to -1.08, p < 0.001), and normal sperm morphology (ß = -0.16, 95%CI: -0.28 to -0.04, p = 0.009), respectively. Taken together, generalized anxiety disorder could significantly influence the clinical semen quality in infertile men in North China, and psychological stress management might be helpful.

A study of diabetes-induced erectile dysfunction treated with human umbilical cord mesenchymal stem cells.

The present study aimed to assess the value of human umbilical cord mesenchymal stem cells (hUC-MSCs) for the treatment of diabetes-induced erectile dysfunction (DMED). We established a type 1 diabetes model through intra-abdominal streptozotocin injection. After 10 weeks, an apomorphine test was performed to screen the rats for erectile dysfunction (ED). The rats were divided into three groups: normal control group (n = 10), DMED group (n = 9) and DMED+hUC-MSC group (n = 9). After 4 weeks of hUC-MSC therapy, erectile function was evaluated by intracavernous pressure measurements, and penile tissue collagen and smooth muscle were examined by haematoxylin-eosin and Masson's trichrome staining. In addition, western blotting, immunohistochemistry and RT-PCR analysis of TLR4, VEGF and eNOS were performed. The results showed that hUC-MSC treatment restored erectile function (p < .05) and reversed the smooth muscle/collagen ratio changes of DMED rats (p < .05). Furthermore, hUC-MSC treatment inhibited the expression of TLR4 (p < .05) and enhanced VEGF and eNOS expression (p < .05). In conclusion, hUC-MSC treatment restored the erectile function of diabetic rats by inhibiting TLR4, improving corpora cavernosa fibrosis, and increasing VEGF and eNOS expression.

Long noncoding RNAs regulated spermatogenesis in varicocele-induced spermatogenic dysfunction.

OBJECTIVES: To evaluate the expression, potential functions and mechanisms of long noncoding RNAs (lncRNAs) in the pathogenesis of varicocele (VC)-induced spermatogenic dysfunction. MATERIALS AND METHODS: We established a rat model with left experimental VC and divided rats into the sham group, the VC group, and the surgical treatment group (each group, n = 10). Haematoxylin and eosin (HE) staining and sperm quality were analysed to evaluate spermatogenesis function. LncRNA expression profiles were analysed using lncRNA-Seq (each group n = 3) and validated using quantitative real-time polymerase chain reaction (each group n = 10). Correlation analysis and gene target miRNA prediction were used to construct competing endogenous RNA network. The regulated signalling pathway and spermatogenic dysfunction of differentially expressed lncRNAs (DE lncRNAs) were validated by Western blot. RESULTS: HE detection and sperm quality analysis showed that VC could induce spermatogenic dysfunction. Eight lncRNAs were upregulated and three lncRNAs were downregulated in the VC group compared with the sham group and surgical treatment group. The lncRNA of NONRATG002949.2, NONRATG001060.2, NONRATG013271.2, NONRATG022879.2, NONRATG023424.2, NONRATG005667.2 and NONRATG010686.2 were significantly negatively related to sperm quality, while NONRATG027523.1, NONRATG017183.2 and NONRATG023747.2 were positively related to sperm quality. The lncRNAs promote spermatogenic cell apoptosis and inhibit spermatogonia and spermatocyte proliferation and meiotic spermatocytes by regulating the PI3K-Akt signalling pathway. CONCLUSION: DE lncRNAs may be potential biomarkers for predicting the risk of spermatogenic dysfunction in VC and the effect of surgical repair. These DE lncRNAs promote spermatogenic dysfunction by regulating the PI3K-Akt signalling pathway.