Stromal lenticule addition keratoplasty with corneal crosslinking for corneal ectasia secondary to FS-LASIK: a case series.

AIM: To explore the clinical efficacy and safety of stromal lenticule addition keratoplasty (SLAK) with corneal crosslinking (CXL) on patients with corneal ectasia secondary to femtosecond laser-assisted in situ keratomileusis (FS-LASIK). METHODS: A series of 5 patients undertaking SLAK with CXL for the treatment of corneal ectasia secondary to FS-LASIK were followed for 4-9mo. The lenticules were collected from patients undertaking small incision lenticule extraction (SMILE) for the correction of myopia. Adding a stromal lenticule was aimed at improving the corneal thickness for the safe application of crosslinking and compensating for the thin cornea to improve its mechanical strength. RESULTS: All surgeries were conducted successfully with no significant complications. Their best corrected visual acuity (BCVA) ranged from 0.05 to 0.8-2 before surgery. The pre-operational total corneal thickness ranged from 345-404 µm and maximum keratometry (Kmax) ranged from 50.8 to 86.3. After the combination surgery, both the corneal keratometry (range 55.9 to 92.8) and total corneal thickness (range 413-482 µm) significantly increased. Four out of 5 patients had improvement of corneal biomechanical parameters (reflected by stiffness parameter A1 in Corvis ST). However, 3 patients showed decreased BCVA after surgery due to the development of irregular astigmatism and transient haze. Despite the onset of corneal edema right after SLAK, the corneal topography and thickness generally stabilized after 3mo. CONCLUSION: SLAK with CXL is a potentially beneficial and safe therapy for advanced corneal ectasia. Future work needs to address the poor predictability of corneal refractometry and compare the outcomes of different surgical modes.

Crown Ether Copolymerized Polyimide Film: Enhanced Mechanical, Thermal Properties and Low Dielectric Constant under High Frequency.

Polymer materials with a low dielectric constant and low dielectric loss have the potential to be applied to high-frequency signal transmissions, such as mobile phone antennas and millimeter wave radars. Two types of diamines, 4,4'-diamino-p-tetraphenyl (DPT) and crown ether diamine (CED), were prepared for ternary copolymerization with BPDA in this study. Cross-links with molecular chains were formed, increasing molecular chain distance by utilizing rings of CED. The MPI films exhibit a good thermal performance with the increase in CED addition, with Tg > 380 °C and CTE from -4 × 10-6 K-1 to 5 × 10-6 K-1. The Young's modulus can reach 8.6 GPa, and the tensile strength is above 200 MPa when 5% and 7% CED are introduced. These MPI films exhibit good mechanical performances. The dielectric constant of PI-10% film can go as low as 3.17. Meanwhile, the relationship between dielectric properties and molecular structure has been demonstrated by Molecular Simulation (MS). PI molecules are separated by low dielectric groups, resulting in a decrease in the dielectric constant.

Corrigendum: Tpr deficiency disrupts erythroid maturation with impaired chromatin condensation in zebrafish embryogenesis.

[This corrects the article DOI: 10.3389/fcell.2021.709923.].

Population pharmacokinetics of adebrelimab - Support of alternative flat dose regimen in extensive-stage small-cell lung cancer.

Adebrelimab, a novel anti-PD-L1 antibody, has been approved by the National Medical Products Administration of China as an intravenous infusion for use in combination with carboplatin and etoposide as first-line treatment for extensive-stage small-cell lung cancer in 2023. A two-compartment model with empirical time-varying CL for adebrelimab was established based on data from 263 patients receiving body weight-based doses from two clinical studies. Significant covariate effects of baseline body weight, albumin levels, tumor size, neutrophil counts, and presence of anti-drug antibodies were identified on CL of debrelimab, none of which were clinically significant or warranted dose adjustment. The degree of decrease in CL was higher in patients who responded to treatment with adebrelimab than in non-responders. Adebrelimab exposures (AUC, Ctrough, or Cmax) were not identified as a statistically significant factor related to efficacy or safety endpoint in the exposure-response analysis. Distribution of simulated exposure metrics from the flat dose regimen (1200 mg q3w) was similar to the marketed weight-based dosing regimen (20 mg/kg q3w), supporting the alternative flat dose regimen in the clinic.

Co-decoction of Lilii bulbus and Radix Rehmannia Recens and its key bioactive ingredient verbascoside inhibit neuroinflammation and intestinal permeability associated with chronic stress-induced depression via the gut microbiota-brain axis.

BACKGROUND: Gut microbiota plays a critical role in the pathogenesis of depression and are a therapeutic target via maintaining the homeostasis of the host through the gut microbiota-brain axis (GMBA). A co-decoction of Lilii bulbus and Radix Rehmannia Recens (LBRD), in which verbascoside is the key active ingredient, improves brain and gastrointestinal function in patients with depression. However, in depression treatment using verbascoside or LBRD, mechanisms underlying the bidirectional communication between the intestine and brain via the GMBA are still unclear. PURPOSE: This study aimed to examine the role of verbascoside in alleviating depression via gut-brain bidirectional communication and to study the possible pathways involved in the GMBA. METHODS: Key molecules and compounds involved in antidepressant action were identified using HPLC and transcriptomic analyses. The antidepressant effects of LBRD and verbascoside were observed in chronic stress induced depression model by behavioural test, neuronal morphology, and synaptic dendrite ultrastructure, and their neuroprotective function was measured in corticosterone (CORT)-stimulated nerve cell injury model. The causal link between the gut microbiota and the LBRD and verbascoside antidepressant efficacy was evaluate via gut microbiota composition analysis and faecal microbiota transplantation (FMT). RESULTS: LBRD and Verbascoside administration ameliorated depression-like behaviours and synaptic damage by reversing gut microbiota disturbance and inhibiting inflammatory responses as the result of impaired intestinal permeability or blood-brain barrier leakiness. Furthermore, verbascoside exerted neuroprotective effects against CORT-induced cytotoxicity in an in vitro depression model. FMT therapy indicated that verbascoside treatment attenuated gut inflammation and central nervous system inflammatory responses, as well as eliminated neurotransmitter and brain-gut peptide deficiencies in the prefrontal cortex by modulating the composition of gut microbiota. Lactobacillus, Parabacteroides, Bifidobacterium, and Ruminococcus might play key roles in the antidepressant effects of LBRD via the GMBA. CONCLUSION: The current study elucidates the multi-component, multi-target, and multi-pathway therapeutic effects of LBRD on depression by remodeling GMBA homeostasis and further verifies the causality between gut microbiota and the antidepressant effects of verbascoside and LBRD.

Circadian Clock in Muscle Disease Etiology and Therapeutic Potential for Duchenne Muscular Dystrophy.

Circadian clock and clock-controlled output pathways exert temporal control in diverse aspects of skeletal muscle physiology, including the maintenance of muscle mass, structure, function, and metabolism. They have emerged as significant players in understanding muscle disease etiology and potential therapeutic avenues, particularly in Duchenne muscular dystrophy (DMD). This review examines the intricate interplay between circadian rhythms and muscle physiology, highlighting how disruptions of circadian regulation may contribute to muscle pathophysiology and the specific mechanisms linking circadian clock dysregulation with DMD. Moreover, we discuss recent advancements in chronobiological research that have shed light on the circadian control of muscle function and its relevance to DMD. Understanding clock output pathways involved in muscle mass and function offers novel insights into the pathogenesis of DMD and unveils promising avenues for therapeutic interventions. We further explore potential chronotherapeutic strategies targeting the circadian clock to ameliorate muscle degeneration which may inform drug development efforts for muscular dystrophy.

Cortical activation for adolescent-onset minor depression and major depressive disorder: an fNIRS study.

BACKGROUND: While depression is increasing worldwide, some patients are diagnosed as having Major Depressive Disorder (MDD), but others are diagnosed with minor depression, however, the potential neuro mechanism is unknown. METHODS: Sixty-two patients with minor depression, 44 adolescents with MDD and 54 healthy adolescents participated in this study. Functional near-infrared spectroscopy (fNIRS), both HAMD and HAMA data were collected from all of the participants. RESULTS: The result indicates the pervasively decreased activation of BA, 11, 21, 45 and 46 were observed in the MDD group and reduced activation of BA 45 was observed in the minor depression group. However, cortical activation was not observed between the minor depression or MDD groups. Cortical activation was also not correlated with the depressive/anxious score in the minor and MDD groups separately. CONCLUSIONS: Cortical activation was pervasively decreased in the MDD group and slightly reduced in the minor depression group, which may be a potential neural mechanism. As reduced cortical activation in minor depression, interventions in the early stages of minor depression may help slow or even modify the development of the illness.

Prevalence, genetic and clinical characteristics in first-degree relatives of patients with familial cerebral cavernous malformations in China.

OBJECTIVE: This study aims to investigate the prevalence of familial cerebral cavernous malformations (FCCMs) in first-degree relatives (FDRs) using familial screening, to describe the distribution of initial symptoms, lesion count on cranial MRI and pathogenic gene in patients. METHODS: Patients with multiple CCMs who enrolled from the Treatments and Outcomes of Untreated Cerebral Cavernous Malformations in China database were considered as probands and FDRs were recruited. Cranial MRI was performed to screen the CCMs lesions, and whole-exome sequencing was performed to identify CCM mutations. MRI and genetic screening were combined to diagnose FCCM in FDRs, and the results were presented as prevalence and 95% CIs. The Kaplan-Meier (KM) method was used to calculate the cumulative incidence of FCCM. RESULTS: 33 (76.74%) of the 43 families (110 FDRs) were identified as FCCM (85 FDRs). Receiver operating characteristic analysis revealed three lesions on T2-weighted imaging (T2WI) were the strong indicator for distinguishing probands with FCCM (sensitivity, 87.10%; specificity, 87.50%). Of the 85 FDRs, 31 were diagnosed with FCCM, resulting in a prevalence of 36.5% (26.2%-46.7%). In families with FCCMs, the mutation rates for CCM1, CCM2 and CCM3 were 45.45%, 21.21% and 9.09%, respectively. Furthermore, 53.13% of patients were asymptomatic, 17.19% were intracranial haemorrhage and 9.38% were epilepsy. The mean age of symptom onset analysed by KM was 46.67 (40.56-52.78) years. CONCLUSION: Based on MRI and genetic analysis, the prevalence of CCMs in the FDRs of families with FCCMs in China was 36.5%. Genetic counselling and MRI screening are recommended for FDRs in patients with more than three CCM lesions on T2WI.

Research on Intelligent Vehicle Trajectory Tracking Control Based on Improved Adaptive MPC.

Intelligent vehicle trajectory tracking exhibits problems such as low adaptability, low tracking accuracy, and poor robustness in complex driving environments with uncertain road conditions. Therefore, an improved method of adaptive model predictive control (AMPC) for trajectory tracking was designed in this study to increase the corresponding tracking accuracy and driving stability of intelligent vehicles under uncertain and complex working conditions. First, based on the unscented Kalman filter, longitudinal speed, yaw speed, and lateral acceleration were considered as the observed variables of the measurement equation to estimate the lateral force of the front and rear tires accurately in real time. Subsequently, an adaptive correction estimation strategy for tire cornering stiffness was designed, an AMPC method was established, and a dynamic prediction time-domain adaptive model was constructed for optimization according to vehicle speed and road adhesion conditions. The improved AMPC method for trajectory tracking was then realized. Finally, the control effectiveness and trajectory tracking accuracy of the proposed AMPC technique were verified via co-simulation using CarSim and MATLAB/Simulink. From the results, a low lateral position error and heading angle error in trajectory tracking were obtained under different vehicle driving conditions and road adhesion conditions, producing high trajectory-tracking control accuracy. Thus, this work provides an important reference for improving the adaptability, robustness, and optimization of intelligent vehicle tracking control systems.

Hypomethylation-associated LINC00987 downregulation induced lung adenocarcinoma progression by inhibiting the phosphorylation-mediated degradation of SND1.

DNA methylation, an epigenetic regulatory mechanism dictating gene transcription, plays a critical role in the occurrence and development of cancer. However, the molecular underpinnings of LINC00987 methylation in the regulation of lung adenocarcinoma (LUAD) remain elusive. This study investigated LINC00987 expression in LUAD patients through analysis of The Cancer Genome Atlas data sets. Quantitative real-time polymerase chain reaction (RT-qPCR) and fluorescence in situ hybridization assays were used to assess LINC00987 expression in LUAD. The bisulfite genomic sequence PCR (BSP) assay was used to determine the methylation levels of the LINC00987 promoter. The interaction between LINC00987 and SND1 was elucidated via immunoprecipitation and RNA pull-down assays. The functional significance of LINC00987 and SND1 in Calu-3 and NCI-H1688 cells was evaluated in vitro through CCK-8, EdU, Transwell, flow cytometry, and vasculogenic mimicry (VM) tube formation assays. LINC00987 expression decreased in LUAD concomitant with hypermethylation of the promoter region, while hypomethylation of the LINC00987 promoter in LUAD tissues correlated with tumor progression. Treatment with 5-Aza-CdR augmented LINC00987 expression and inhibited tumor growth. Mechanistically, LINC00987 overexpression impeded LUAD progression and VM through direct binding with SND1, thereby facilitating its phosphorylation and subsequent degradation. Additionally, overexpression of SND1 counteracted the adverse effects of LINC00987 downregulation on cell proliferation, apoptosis, cell migration, invasion, and VM in LUAD in vitro. In conclusion, this pioneering study focuses on the expression and function of LINC00987 and reveals that hypermethylation of the LINC00987 gene may contribute to LUAD progression. LINC00987 has emerged as a potential tumor suppressor gene in tumorigenesis through its binding with SND1 to facilitate its phosphorylation and subsequent degradation.

Advances in stem cells treatment of diabetic wounds: A bibliometric analysis via CiteSpace.

Diabetes is a chronic medical condition that may induce complications such as poor wound healing. Stem cell therapies have shown promise in treating diabetic wounds with pre-clinical and clinical studies. However, little bibliometric analysis has been carried out on stem cells in the treatment of diabetic wounds. In this study, we retrieved relevant papers published from January 1, 2003, to December 31, 2023, from Chinese and English databases. CiteSpace software was used to analyze the authors, institutions, and keywords by standard bibliometric indicators. Our analysis findings indicated that publications on stem cells in the treatment of diabetic wounds kept increasing. The most prolific author was Qian Cai (n = 7) and Mohammad Bayat (n = 16) in Chinese and English databases, respectively. Institutions distribution analysis showed that Chinese institutions conducted most publications, and the most prolific institution was the Chinese People's Liberation Army General Hospital (n = 9) and Shahid Beheshti University of Medical Sciences (n = 17) in Chinese and English databases, respectively. The highest centrality keyword in Chinese and English databases was "wound healing" (0.54) and "in vitro" (0.13), respectively. There were 8 and 11 efficient and convincing keyword clusters produced by a log-likelihood ratio in the Chinese and English databases, respectively. The strongest burst keyword was "exosome" (strength 3.57) and "endothelial progenitor cells" (strength 7.87) in the Chinese and English databases, respectively. These findings indicated a direction for future therapies and research on stem cells in the treatment of diabetic wounds.

Social exclusion in a virtual Cyberball game reduces the virtual hand illusion.

Sense of ownership and agency are two important aspects of the minimal self, but how self-perception is affected by social conditions remains unclear. Here, we studied how social inclusion or exclusion of participants in the course of a virtual Cyberball game would affect explicit judgments and implicit measures of ownership and agency (proprioceptive drift, skin conductance responses, and intentional binding, respectively) in a virtual hand illusion paradigm, in which a virtual hand moved in or out of sync with the participants' own hand. Results show that synchrony affected all four measures. More importantly, this effect interacted with social inclusion/exclusion in the Cyberball game for both ownership and agency measure, showing that social exclusion reduces perceived agency and ownership.

Current Status of Cognition and Clinical Practice of Refractory Cancer Pain in Shanghai: A Questionnaire Survey.

Purpose: This study aimed to assess the current status of clinical practice of refractory cancer pain (RCP) among a sample of physicians specializing in cancer pain management in Shanghai. Methods: From 2019 to 2021, a questionnaire survey was conducted among physicians engaged in diagnosis and treatment of cancer pain through the questionnaire WJX network platform in Shanghai, China. Results: A total of 238 responses participated in the survey. This survey reports physicians' understanding and incidence rate of breakthrough cancer pain (BTCP). The choice of analgesics and satisfaction of analgesic effect were investigated. We also investigated doctors' knowledge of the diagnostic criteria for RCP and their tendency to choose analgesics. Oral immediate-release morphine and intravenous or subcutaneous morphine injection have been the common treatment approach for transient cancer pain exacerbations. The main barriers to pain management are lack of standardized treatment methods for RCP, lack of knowledge related to RCP, and single drug dosage form. Doctors believe the most necessary measures to improve the current situation of poor cancer pain control include improving medical staff's understanding and treatment techniques for RCP, updating treatment techniques and methods, and improving the configuration of drug types in medical institutions. Clinicians expect to improve understanding and treatment techniques through systematic training. Conclusion: Despite multiple available analgesic measures, the treatment of RCP remains challenging. Improving the understanding of medical staff towards RCP, improving treatment techniques, and increasing the accessibility of multiple drug types are important ways to improve the satisfaction of cancer pain management in the future.

Failure mechanism and bearing force of CFRP strengthened square hollow section under compressive load.

Carbon fibre-reinforced polymer (CFRP) plates can efficiently repair or enhance the mechanical properties of the square hollow section. However, the loading end of such a CFRP-strengthened member is prone to local bearing failure under compressive load. Given this limitation, an innovative CFRP-plate-strengthened square hollow section composite member (CFRP-SHSCM) was raised, and the thick-walled section was welded on both ends of the thin-walled steel column. The mechanical properties of CFRP-SHSCMs were investigated through parameter finite element (FE) analysis, focusing on the influence of the amount of CFRP layers (nc), the slenderness ratio (λ), the initial geometric imperfections (v0), the CFRP layouts (2S and 4S) and the length of the exposed steel column (Le). The load-displacement curves, the bearing force, and typical failure modes were also acquired. Results indicated that with increasing nc and v0, and decreasing λ, the conventional CFRP-SHSCMs were prone to local bearing failure with poor ductility, leading to the insufficient use of the CFRP plate, in contrast, the improved CFRP-SHSCMs primarily underwent overall buckling failure and exhibited better bearing force and ductility. Finally, the modified Perry-Robertson formula was put forward to predict the ultimate load of the CFRP-SHSCMs. The coefficients of variation between the FE simulation and the theoretical results were 0.00436 and 0.0292, respectively.

The Bidirectional Relationship between Weight Gain and Cognitive Function in First-Episode Schizophrenia: A Longitudinal Study in China.

Patients with schizophrenia often encounter notable weight gain during their illness, heightening the risk of metabolic diseases. While previous studies have noted a correlation between obesity and cognitive impairment in schizophrenia, many were cross-sectional, posing challenges in establishing a causal relationship between weight gain and cognitive function. The aim of this longitudinal study is to examine the relationship between weight gain and cognitive function in patients with first-episode schizophrenia (FES) during the initial 6-month antipsychotic treatments. Employing linear and logistic regression analyses, the study involved 337 participants. Significantly, baseline scores in processing speed (OR = 0.834, p = 0.007), working memory and attention (OR = 0.889, p = 0.043), and executive function (OR = 0.862, p = 0.006) were associated with clinically relevant weight gain (CRW, defined as an increase in body weight > 7%) at the 6-month endpoint. On the other hand, CRW correlated with improvements in the Brief Visuospatial Memory Test (p = 0.037). These findings suggest that patients with lower baseline cognitive performance undergo more substantial weight gain. Conversely, weight gain was correlated with cognitive improvements, particularly in the domain of visual learning and memory. This suggested a potential bidirectional relationship between weight gain and cognitive function in first-episode schizophrenia patients.

Corrigendum: Mutation of Gemin5 causes defective hematopoietic stem/progenitor cells proliferation in zebrafish embryonic hematopoiesis.

[This corrects the article DOI: 10.3389/fcell.2021.670654.].

Cancer Methylation Biomarker Detection in an Automated, Portable, Multichannel Magnetofluidic Platform.

Early detection of cancer is critical to improving clinical outcomes, especially in territories with limited healthcare resources. DNA methylation biomarkers have shown promise in early cancer detection, but typical workflows require highly trained personnel and specialized equipment for manual and lengthy processing, limiting use in resource-constrained areas. As a potential solution, we introduce the Automated Cartridge-based Cancer Early Screening System (ACCESS), a compact, portable, multiplexed, automated platform that performs droplet magnetofluidic- and methylation-specific qPCR-based assays for the detection of DNA methylation cancer biomarkers. Development of ACCESS focuses on esophageal cancer, which is among the most prevalent cancers in low- and middle-income countries with extremely low survival rates. Upon implementing detection assays for two esophageal cancer methylation biomarkers within ACCESS, we demonstrated successful detection of both biomarkers from esophageal tumor tissue samples from eight esophageal cancer patients while showing specificity in paired normal esophageal tissue samples. These results illustrate ACCESS's potential as an amenable epigenetic diagnostic tool for resource-constrained areas toward early detection of esophageal cancer and potentially other malignancies.

Anti-pancreatic cancer activity of cassane diterpenoids isolated from the seeds of Caesalpinia sappan mediated by autophagy activation via ROS/AMPK/mTORC1 pathway.

Three undescribed cassane diterpenoids, caesalpanins D-F (1-3), and seven known ones were isolated from the seeds of Caesalpinia sappan. Structures and absolute configurations of 1-3 were elucidated based on the extensive spectroscopic analysis, single-crystal X-ray diffraction analysis, and ECD calculations. Structurally, compound 1 was the first example of 18-norcassane diterpenoid and 2 was a rare 20-norcassane diterpenoid having an unusual five-membered oxygen bridge between C-10/C-18. The anti-proliferative activity of 1, 3, and 4-10 against PANC-1 cells (pancreatic ductal adenocarcinoma cell line) was evaluated, and phanginin H (4) was found to exhibit anti-cancer activity with IC50 value of 18.13 ± 0.63 µM. Compound 4 inhibited PANC-1 cell growth by arresting the cell cycle at G2/M phase via regulation of cyclin-dependent kinases, and the self-renewal and metastasis of PANC-1 cells by suppressing cancer cell stemness. Furthermore, compound 4 induced ROS generation and subsequently activated autophagy, which was demonstrated by the formation of autophagic vacuoles and dynamic change of autophagic flux. The induced ROS accumulation resulted in AMPK activation and subsequently regulation of mTORC1 activity and ULK phosphorylation, indicating that 4 triggered autophagy through ROS/AMPK/mTORC1 pathway. These findings suggested that 4 might potentially be an autophagy inducer for the therapy of pancreatic cancer.

PPRTGI: A Personalized PageRank Graph Neural Network for TF-target Gene Interaction Detection.

Transcription factors (TFs) regulation is required for the vast majority of biological processes in living organisms. Some diseases may be caused by improper transcriptional regulation. Identifying the target genes of TFs is thus critical for understanding cellular processes and analyzing disease molecular mechanisms. Computational approaches can be challenging to employ when attempting to predict potential interactions between TFs and target genes. In this paper, we present a novel graph model (PPRTGI) for detecting TF-target gene interactions using DNA sequence features. Feature representations of TFs and target genes are extracted from sequence embeddings and biological associations. Then, by combining the aggregated node feature with graph structure, PPRTGI uses a graph neural network with personalized PageRank to learn interaction patterns. Finally, a bilinear decoder is applied to predict interaction scores between TF and target gene nodes. We designed experiments on six datasets from different species. The experimental results show that PPRTGI is effective in regulatory interaction inference, with our proposed model achieving an area under receiver operating characteristic score of 93.87% and an area under precision-recall curves score of 88.79% on the human dataset. This paper proposes a new method for predicting TF-target gene interactions, which provides new insights into modeling molecular networks and can thus be used to gain a better understanding of complex biological systems.

Nitric oxide-induced lipophagic defects contribute to testosterone deficiency in rats with spinal cord injury.

Introduction: Males with acute spinal cord injury (SCI) frequently exhibit testosterone deficiency and reproductive dysfunction. While such incidence rates are high in chronic patients, the underlying mechanisms remain elusive. Methods and results: Herein, we generated a rat SCI model, which recapitulated complications in human males, including low testosterone levels and spermatogenic disorders. Proteomics analyses showed that the differentially expressed proteins were mostly enriched in lipid metabolism and steroid metabolism and biosynthesis. In SCI rats, we observed that testicular nitric oxide (NO) levels were elevated and lipid droplet-autophagosome co-localization in testicular interstitial cells was decreased. We hypothesized that NO impaired lipophagy in Leydig cells (LCs) to disrupt testosterone biosynthesis and spermatogenesis. As postulated, exogenous NO donor (S-nitroso-N-acetylpenicillamine (SNAP)) treatment markedly raised NO levels and disturbed lipophagy via the AMPK/mTOR/ULK1 pathway, and ultimately impaired testosterone production in mouse LCs. However, such alterations were not fully observed when cells were treated with an endogenous NO donor (L-arginine), suggesting that mouse LCs were devoid of an endogenous NO-production system. Alternatively, activated (M1) macrophages were predominant NO sources, as inducible NO synthase inhibition attenuated lipophagic defects and testosterone insufficiency in LCs in a macrophage-LC co-culture system. In scavenging NO (2-4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (CPTIO)) we effectively restored lipophagy and testosterone levels both in vitro and in vivo, and importantly, spermatogenesis in vivo. Autophagy activation by LYN-1604 also promoted lipid degradation and testosterone synthesis. Discussion: In summary, we showed that NO-disrupted-lipophagy caused testosterone deficiency following SCI, and NO clearance or autophagy activation could be effective in preventing reproductive dysfunction in males with SCI.