High-fat diets (HFDs) are frequently used in aquaculture to enhance feed efficiency, yet they often induce hepatic steatosis by disrupting the balance between lipogenesis and lipolysis. In mammals, activation of the farnesoid X receptor (Fxr) alleviates hepatic lipid accumulation by modulating fibroblast growth factor 19 (Fgf19) expression, which in turn regulates lipid homeostasis. However, the molecular characteristics and regulatory mechanisms of Fgf19 in fishes remains poorly defined. In this study, we investigated the role of Fxr in hepatic lipid metabolism in yellow catfish (Pelteobagrus fulvidraco) fed a HFD, using the Fxr agonist GW4064. Our in vivo experiments demonstrated that while the HFD reduced growth and increased hepatic fat deposition, GW4064 supplementation reduced liver triglyceride and non-esterified fatty acid levels, restored the balance between lipogenesis and lipolysis, and alleviated oxidative stress. In vitro assays with primary hepatocytes confirmed these results, showing that Fxr activation via GW4064 lowered lipid accumulation and improved cellular redox status. Furthermore, the GW4064 treatment elevated the fgf19 and fgfr4 genes expression levels, and Fgf19 content. We also cloned the yellow catfish fgf19 gene and characterized a 1700 bp promoter region containing several transcription factor binding sites, including a critical Fxr element essential for fgf19 transcriptional activation. Deletion and mutational analysis revealed that Fxr directly activates fgf19 transcription by binding to the −354 to −345 bp site of the fgf19 gene promoter. Recombinant Fgf19 application reduced lipid deposition in hepatocytes by modulating key lipogenic and lipolytic genes, an effect that was disrupted upon inhibition of fibroblast growth factor receptor 4 (Fgfr4). Collectively, our findings indicate that Fxr activation modulates liver lipid metabolism in yellow catfish via the Fgf19-Fgfr4 signaling axis, providing novel insights and a potential therapeutic target for combating fatty liver disease in aquaculture.

ABSTRACT Objective Operation for thoracic spinal stenosis (TSS) is considered a high‐risk surgery. Because of the frailty of elderly patients, the prediction for postoperative complications is crucial. This study investigated the relationship between frailty, as measured by the modified frailty index‐11 (mFI‐11), and postoperative complications in elderly patients with thoracic myelopathy secondary to TSS. Methods A retrospective review was conducted of 391 patients aged 65 years or older, with 209 males and 182 females, who underwent surgery for TSS at Peking University Third Hospital from 2012 to 2023. Patients were stratified into subgroups based on mFI‐11 score. Data on perioperative complications, including systemic and local events, were collected. Univariate and multivariate analyses were performed to determine the association between frailty and perioperative complications and to identify independent risk factors. Results A total of 391 elderly patients undergoing decompression and fusion for TSS were included and categorized by mFI‐11 score: 0 ( n = 73), 0.09 ( n = 159), 0.18 ( n = 98), and ≥ 0.27 ( n = 61). Multivariate analysis identified the mFI‐11 as an independent risk factor for surgical site infection (SSI) (OR = 7.250, p = 0.022), gastrointestinal complications (OR = 2.461, p = 0.029), urologic complications (OR = 4.855, p = 0.001), respiratory complications (OR = 13.968, p = 0.033), postoperative fever (OR = 2.256, p < 0.001), and postoperative transfusion (OR = 1.962, p = 0.014). Moreover, mFI ≥ 0.27 is a threshold for severe complications (OR = 15.886, p = 0.017), and mFI ≥ 0.18 is a threshold for any postoperative complications (OR = 6.338, p < 0.001) and minor complications (OR = 5.915, p < 0.001). Conclusions The mFI‐11 score is an effective predictor of the risk of surgical site infection, gastrointestinal complications, urologic complications, respiratory complications, postoperative fever, and postoperative transfusion in elderly patients undergoing TSS surgery. Patients with mFI scores ≥ 0.18 are at a significantly higher risk of any postoperative complications or minor complications, with mFI scores ≥ 0.27 indicating severe complications. Frailty, as assessed by mFI‐11, and non‐neurological complications did not significantly impact the long‐term recovery rate.

Study DesignProspective cohort study.ObjectivePostoperative cerebrospinal fluid leakage (CSFL) is a common complication following thoracic spinal stenosis (TSS) surgery. This study aimed to evaluate the therapeutic effects of different fluid supplementation strategies on intracranial hypotension symptoms (IHS) caused by CSFL.MethodsPatients who developed CSFL after TSS surgery at a single center over a 3-year period were prospectively enrolled. All patients received standardized postural and drainage management. In addition, they were administered either low-sodium or high-sodium solution supplementation alongside standard medications. The incidence and severity of IHS and changes of blood electrolyte levels were compared between the two groups.ResultsThe incidence of IHS in low-sodium group is 57.5%, and in high-sodium group is 40% (P = .117). Although, there was no statistically significant difference in the improvement of IHS between the two fluid supplementation strategies. However, statistical differences in blood electrolyte levels were observed. On postoperative days 2 and 3, serum sodium levels were significantly lower in the low-sodium group (139.9 ± 2.08 vs 141.1 ± 3.1, P = .022; 140.0 ± 3.0 vs 141.25 ± 3.85, P = .034).ConclusionWhile high-sodium fluid supplementation tended to reduce the incidence of IHS following CSFL, the difference compared to low-sodium fluids was not statistically significant. Nonetheless, the observed differences in electrolyte level of sodium suggest a potential physiological impact. Further studies with larger sample sizes are needed to confirm these findings.

The "Warburg effect", a hallmark of Osteosarcoma(OS), results in lactate accumulation due to aerobic glycolysis. The role and underlying mechanisms of lactate in OS are not well understood. Herein, the lactate-activated hydroxycarboxylate receptor 1(HCAR1) is found to promote OS progression via inhibiting the transcription of anti-oncogene downstream of STAT1/2. The phosphorylation level of STAT1/2 holds considerable significance for transcriptional activity. In this study, protein phosphatase 2A(PP2A) is identified as the tyrosine phosphatase of STAT1/2. Lactate-activated HCAR1, facilitating PP2A interaction with phosphorylated STAT1/2 via β-Arrestin 2, resulting in STAT1/2 dephosphorylation, a key process linked to the aggressive behavior of OS. Using PP2A inhibitor Endothall can abolish the dephosphorylation effect of HCAR1 on STAT1/2, inhibit cancer cell proliferation, migration, and cell cycle, and promote apoptosis. Moreover, the combination of Endothall and Cisplatin is high synergistic in treating OS. In conclusion, the study elucidates the pro-oncogenic role of lactate-activated HCAR1 in OS.

BACKGROUND:High-fat diets (HFDs) can lead to excessive accumulation of lipids in the liver, leading to liver injury. Dietary zinc (Zn) has been shown to reduce HFD-induced lipid accumulation and improve lipid profiles in mammals, yet it remains unclear whether waterborne Zn maintains its lipid-lowering effects in osteichthyes. OBJECTIVES:This study aimed to elucidate the regulatory role of Zn in HFD-induced hepatic lipid accumulation in yellow catfish (Pelteobagrus fulvidraco) and its potential mechanisms. METHODS:Yellow catfish were fed a control diet (11.21% lipid concentration), HFD (16.10% lipid concentration), or HFD combined with waterborne Zn exposure (0.2 mg/L) for 8 wk. Various biochemical, genetic, histologic, and molecular techniques were conducted to evaluate hepatic lipid deposition and lipid metabolism and determine protein interactions between silent information regulator (SIRT) 1 and farnesoid X receptor (FXR), as well as protein-gene interactions between FXR and adipose triglyceride lipase (ATGL). RESULTS:HFD feeding significantly increased liver fat content and induced hepatic damage in yellow catfish, but concurrent exposure to waterborne Zn alleviated these detrimental effects. Zn treatment increased mRNA and protein concentrations of SIRT1 (mean ± SEM; 97.19% ± 11.67% and 83.25% ± 28.60%, respectively) and FXR (163.90% ± 24.60% and 24.90% ± 11.12%, respectively) in yellow catfish liver (P < 0.05). Zn-activated FXR directly interacted with the promoter of ATGL, stimulating the expression of atgl (54.40% ± 16.33%; P < 0.05) and facilitating the hydrolysis of triglycerides and lipid droplets. Furthermore, Zn reduced the acetylation concentration of FXR by SIRT1 deacetylation of FXR protein K167. CONCLUSIONS:The findings reveal that Zn protect against HFD-induced liver injury in yellow catfish by promoting the deacetylation of FXR protein K167 by SIRT1 and activating FXR, thereby promoting the transcriptional activation of ATGL to increase lipolysis.

PURPOSE:There are many causes of thoracic ossification of the ligamentum flavum (TOLF), of which mechanical stress factors have gained increasing attention. This study aimed to explore the potential pathogenesis of TOLF by comparing spinal sagittal alignment parameters between patients with TOLF and an asymptomatic population. METHODS:We retrospectively included patients who underwent surgical treatment for thoracic myelopathy caused by OLF at Peking University Third Hospital from 2012 to 2022. Sagittal alignment parameters measured by picture archiving and communication system were compared between the TOLF group and a control group with independent t-test, Wilcoxon rank-sum test, and Chi-Squared test. Patients with caudal insertion of OLF above the T10 level were categorized into Group 1, while those with caudal insertion below the T10 level were categorized into Group 2. Sagittal alignment parameters were then compared among these two groups and the control group. RESULTS:Compared with the control group, the OLF group exhibited less lumbar lordosis (44.46° ± 11.41° vs. 52.55° ± 9.70°, p < 0.001), greater thoracolumbar curvature, greater PI-LL mismatch, and greater SVA imbalance. In patients with caudal insertion of the OLF above the T10 level, PI, PT, and LL were smaller compared to the control group. Patients with caudal insertion below the T10 level had smaller LL, greater thoracolumbar kyphosis, more severe SVA imbalance, and more severe PI-LL mismatch. CONCLUSION:Patients with TOLF have a straighter spine. Mechanical stress plays a more significant role in the development of TOLF in patients with caudal lesions below the T10 level. In patients with TOLF not involving the thoracolumbar segment, factors other than mechanical stress, such as endocrine factors, may play a more crucial role in the development of TOLF.

Oxeiptosis is a reactive oxygen species (ROS)-induced pathway of cell death. The involvement of circular RNAs (circRNAs) has been confirmed in the incidence and progression of intervertebral disc degeneration (IVDD). However, whether oxeiptosis occurs in IVDD and how circRNAs regulate oxeiptosis is still unclear. In this study, we discovered that oxeiptosis could be induced in nucleus pulposus cells (NPCs), and circFOXO3 was significantly upregulated after oxeiptosis induction. Transfection using circFOXO3 small interfering RNA (siRNA) significantly inhibited oxeiptosis in NPCs. Mechanistically, circFOXO3 upregulated acid-sensing ion channel subunit 1 (ASIC1) expression by functioning as a molecular sponge for miR-185-3p and miR-939-5p. Subsequent rescue experiments validated that circFOXO3 could regulate oxeiptosis in NPCs via the miR-185-3p/miR-939-5p-ASIC1 axis. Further research on ASIC1 functions indicated that this regulation was achieved by affecting the Calcium ion (Ca2+) influx mediated by ASIC1. A mouse IVDD model was established, and silencing circFOXO3 in vivo was found to inhibit IVDD development and the activation of the oxeiptosis-related pathway. Overall, circFOXO3 is one of the factors contributing to the progression of IVDD by mediating oxeiptosis.

Abstract Background M1 macrophages (Mφs) are involved in osteogenic differentiation of ligamentum flavum (LF) cells and play an important role in heterotopic ossification. However, the mechanism by which M1 Mφs influence osteogenic differentiation of LF cells has not been studied. Methods The effect of conditioned medium including secretions of M1 Mφs (CM‐M1) on LF cells was analyzed by GeneChip profiling and ingenuity pathway analysis (IPA). THP‐1 cells were polarized into M1 Mφs and CM‐M1 was used to induce LF cells. In addition, LF cells were induced by CM‐M1 in the presence of cyclooxygenase 2 (COX‐2) inhibitors or oncostatin M (OSM)‐neutralizing antibodies. Based on the presence of OSM, knockout of OSMR or GP130 receptors, or addition of the Janus kinase 2 (JAK2) inhibitor AZD1480 or signal transducer and activator of transcription 3 (STAT3) inhibitor Stattic were examined for effects on osteogenic differentiation of LF cells. OSM secretion was quantified by ELISA, while qPCR and western blot were used to evaluate expression of osteogenic genes and receptor and signaling pathway‐related proteins, respectively. Results GeneChip and IPA results indicate that the OSM signaling pathway and its downstream signaling molecules JAK2 and STAT3 are significantly activated. ELISA results indicate that OSM is highly expressed in cells treated with CM‐M1 and lowly expressed in cells treated with CM‐M1 and a COX‐2 inhibitor. Besides, CM‐M1 induces osteogenic differentiation of LF cells, which is weakened when COX‐2 inhibitors or OSM‐neutralizing antibody are added to it. Recombinant OSM could induce osteogenic differentiation of LF cells and upregulate expression of OSMR, GP130, phosphorylated (P)‐JAK2, and P‐STAT3. Upon knockdown of OSMR or GP130, or the addition of AZD1480 or Stattic, P‐JAK2 and P‐STAT3 expression were decreased and osteogenic differentiation was reduced. Conclusion M1 Mφ‐derived OSM induces osteogenic differentiation of LF cells and the JAK2/STAT3 signaling pathway plays an important role.

OBJECTIVE: To describe a novel technique, posterior thoracic antidisplacement and fusion (PTAF), for a special type of ossification of the posterior longitudinal ligament in the thoracic spine (T-OPLL), and to evaluate its safety and efficacy. METHODS: From July to December 2020, 5 consecutive patients with beak-type T-OPLL located at the thoracic vertebral body level underwent PTAF surgery. Their demographic data, radiological parameters, perioperative complications, and surgery-related findings were recorded and analyzed. The surgical outcomes were assessed using a modified Japanese Orthopedic Association scale, and the recovery rate was calculated using the Hirabayashi's method. RESULTS: All patients were followed up for at least two years. The mean thickness of OPLL was 9.4 +/- 1.0 mm, and the OPLL spinal canal occupying ratio was 67.7% +/- 8.5%. Postoperatively, the mean antidisplacement distance of OPLL was 8.1 +/- 1.8 mm, and the average shortened distance of the spinal column was 6.0 +/- 1.13 mm. The mean operation time and blood loss were 158.2 +/- 26.3 minutes and 460 +/- 89.4 mL, respectively. Perioperative complications were cerebrospinal fluid leakage and instrument failure, 2 cases each. The mean modified Japanese Orthopedic Association score was increased from 3.6 +/- 2.9 before surgery to 9.4 +/- 3.0 at the last follow-up, and the average recovery rate was 84.2 +/- 30.5%. CONCLUSIONS: The preliminary clinical outcomes indicate that PTAF is a safe and effective method for the treatment of beak-type T-OPLL, which has its apex located at the vertebral body level and has a high spinal canal occupation ratio.

Sulfamethoxazole (SMZ) and zinc (Zn) are widespread harmful materials in aquatic ecosystems and cause toxic effects to aquatic animals under their individual exposure. Although they often co-exist in aquatic environments, little is known about their joint effects and mechanism influencing aquatic animals. Herein, SMZ induced mitochondrial and lysosomal dysfunction, inhibited autophagy flux, and induced lipotoxicity. However, SMZ-induced changes of these physiological and metabolic processes above were reversed by Zn exposure, indicating the antagonism between Zn and SMZ. SOD1-knockdown abrogated the reversing effects of Zn on mitochondria dysfunction and autophagy flux blockage induced by SMZ, suggesting that SOD1 was essential for Zn to reverse SMZ-induced mitochondria dysfunction and autophagy impairment. Our further investigation found that Zn regulated STAT3 translocation to lysosomes and mitochondria to attenuate SMZ-induced lipotoxicity, and SOD1 was required for these processes. Mechanistically, STAT3 was associated with ATP6V1 A in a coiled-coil domain-dependent manner, and pS710-STAT3-and pY753-STAT3-independent manners. Moreover, SMZ suppressed autophagic degradation of damaged mitochondria via inhibiting interaction between STAT3 and ATP6V1 A and increasing pS710-STAT3 level; SMZ impaired mitochondrial β-oxidation via decreasing pY753-STAT3 level and STAT3 mitochondrial localization. Zn reversed these SMZ-induced effects to alleviate SMZ-induced lipotoxicity. Taken together, our data showed that SMZ impaired mitochondrial β-oxidation and lysosomal acidification via the downregulation of SOD1, leading to lipotoxicity, and that Zn reversed SMZ-induced changes of these important biological processes and attenuated SMZ-induced lipotoxicity. Thus, our study identified previously unidentified mechanisms for the antagonistic mechanisms of Zn and SMZ on aquatic animals, which provided novel insights into the environmental risk assessments of the joint exposure between heavy metals and antibiotics in the aquatic organisms.

STUDY DESIGN:Retrospective cohort study. OBJECTIVES:To describe the clinical characteristics and surgical outcomes of patients with multilevel-ossification of the posterior longitudinal ligament (mT-OPLL), and to identify risk factors for unfavorable outcomes. METHODS:Patients who were diagnosed with mT-OPLL and underwent one-stage thoracic posterior laminectomy combined with selective OPLL resection, spinal cord de-tension, and fusion surgery between August 2012 and October 2020 were recruited. Patients' demographic-, surgical- and radiological-related parameters were collected and analyzed. Neurological status was evaluated with mJOA score, and recovery rate (RR) was calculated using the Hirabayashi formula. According to RR, patients were divided into a favorable outcome group (FOG, RR ≥50%) and an unfavorable outcome group (UOG, RR <50%). Univariate and multivariate analyses were used to compare the difference between the 2 groups and to identify risk factors for unfavorable outcomes. RESULTS:A total of 83 patients were included, with an average age of 50.6 ± 8.3 years. Cerebrospinal fluid leakage (60.2%) and transient neurological deterioration (9.6%) were the most common complications. The average mJOA score improved from preoperative 4.3 ± 2.2 to 9.0 ± 2.4 at the last follow-up, and the mean RR was 74.9 ± 26.3%. Disease duration, preoperative nonambulatory status, and the number of decompressed levels were identified as potential risk factors by Univariate analysis (all P < .05). Multivariate analysis showed that the preoperative disease duration and nonambulatory status were independent risk factors for unfavorable outcomes. CONCLUSIONS:Long disease duration and nonambulatory status before surgery were independent risk factors for unfavorable outcomes.

Background: Dural ossification (DO) is the leading cause of surgery-related dural tear in patients with ossification of the ligamentum flavum (OLF). An accurate preoperative diagnosis of DO is conducive to the selection of appropriate surgical methods. Although several imaging signs, such as Banner cloud sign (BCs), tram-track sign (TTs), and comma sign (Cs) have been proposed for the preoperative diagnosis of DO, their diagnostic value has not been well studied. The aim of this study was to explore the diagnostic value of BCs, TTs, and Cs, and provide evidence-based data for their clinical application. Methods: This is a blind, randomized diagnostic study using retrospectively collected data from 102 consecutive patients who were diagnosed with OLF and underwent decompression surgery between January 2018 and June 2019. A total of 8 surgeons with different qualifications were recruited to read these imaging signs to identify the presence of DO. Surgical records were used as the reference standard. Sensitivity, specificity, and the area under the receiver operating characteristic (ROC) curve (AUC) were used to evaluate the diagnostic accuracy of each imaging sign and their different combinations.Results: Of the 102 patients, 21 were diagnosed with DO. BCs had a significantly higher diagnostic accuracy than TTs and Cs, with the AUC of 0.704, 0.607, and 0.593, respectively. The specificity of BCs, Cs, TTs, and their combination in diagnosing DO was 91.5%, 92.1%, 68.3%, and 62.2%, respectively. In the combined diagnostic test, the results showed that the combined diagnosis accuracy of BCs and Cs was the highest, and the AUC was 0.738. The combination of BCs, Cs, and TTs increased the sensitivity of diagnosing DO (77.5%), but did not improve the diagnostic accuracy, and the AUC was 0.699. Conclusions: BCs had higher diagnostic accuracy than TTs and Cs. BCs and Cs were highly specific for DO, whereas TTs could be confusing due to their non-specific presentations. The combination of BCs, TTs, and Cs improved the sensitivity of DO diagnosis, but not the specificity and accuracy.

Purpose Dural ossification (DO) is common in patients with ossification of the ligamentum flavum (OLF) and is the leading cause of dural tears. However, the methods used for DO diagnosis are limited. The purpose of this study was to propose a novel CT-based imaging sign, Banner cloud sign (BCs), and clarify its clinical characteristics and correlations with DO. Methods 57 OLF patients who underwent thoracic spine decompression surgery in our single-center between January- and October-2018 were recruited and divided into two groups based on the presence of DO. Patient demographics and radiographic data were analyzed. Hematoxylin-eosin staining and micro-CT were used to detect the micro-morphological changes of DO. The diagnostic value of BCs for DO was assessed by sensitivity and specificity. Results 12 patients with a total of 19 segments were diagnosed as DO. The incidence of DO was 21.1% (12/57) in OLF patients and 9.5% (19/200) in OLF segments. Patients with DO had a shorter disease duration and a higher incidence of cerebrospinal fluid leakage than those without DO. Hematoxylin-eosin staining and micro-CT showed that the dura mater was ossified and fused with ossified ligamentum flavum, and diffusion along the dura mater, like a banner cloud flying on the mountain. The sensitivity and specificity of BCs in DO diagnosis were 78.9 and 90.6%, respectively. Conclusion BCs can vividly and intuitively describe the imaging features of DO and has high diagnostic accuracy. It could be a promising and valuable method for the diagnosis of DO.

Due to many special characteristics, zinc oxide nanoparticles (ZnO NPs) are widely used all over the world, leading to their wide distribution in the environment. However, the toxicities and mechanisms of environmental ZnO NP-induced changes of physiological processes and metabolism remain largely unknown. Here, we found that addition of dietary ZnO NPs disturbed hepatic Zn metabolism, increased hepatic Zn and lipid accumulation, downregulated lipolysis, induced oxidative stress, and activated mitophagy; N,N,N',N'-tetrakis (2-pyridylmethyl) ethylenediamine (TPEN, Zn2+ ions chelator) alleviated high ZnO NP-induced Zn and lipid accumulation, oxidative stress, and mitophagy. Mechanistically, the suppression of mitochondrial oxidative stress attenuated ZnO NP-activated mitophagy and ZnO NP-induced lipotoxicity. Taken together, our study elucidated that mitochondrial oxidative stress mediated ZnO NP-induced mitophagy and lipotoxicity; ZnO NPs could be dissociated to free Zn2+ ions, which partially contributed to ZnO NP-induced changes in oxidative stress, mitophagy, and lipid metabolism. Our study provides novel insights into the impacts and mechanism of ZnO NPs as harmful substances inducing lipotoxicity of aquatic organisms, and accordingly, metabolism-relevant parameters will be useful for the risk assessment of nanoparticle materials in the environment.

Thoracic ossification of the ligamentum flavum (TOLF) is ectopic ossification of the spinal ligaments. Histologically, the development of TOLF can be described as the process of endochondral ossification. However, the underlying aetiology has not been completely clarified. In this investigation, the gene expression profile associated with leucine-rich repeat-containing G-protein-coupled receptors (LGR) and Wnt signalling pathway in the thoracic ligamentum flavum cells (TLFCs) of different ossification stages was analysed via RNA sequencing. We further confirmed the significant differences in the related gene expression profile by Gene Ontology (GO) enrichment analysis. LGR5 was first identified in primary human TLFCs during osteogenic differentiation. To evaluate the effect of LGR5 on osteogenic differentiation, LGR5 has been knocked down and overexpressed in human TLFCs. We observed that the knockdown of LGR5 inhibited the activity of Wnt signalling and attenuated the potential osteogenic differentiation of TLFCs, while overexpression of LGR5 activated the Wnt signalling pathway and increased osteogenic differentiation. Our results provide important evidence for the potent positive mediatory effects of LGR5 on osteogenesis by enhancing the Wnt signalling pathway in TOLF.

Background: Diffuse idiopathic skeletal hyperostosis (DISH) has been evaluated as a potential risk factor of poor surgical outcomes for lumbar spinal stenosis, whereas the influence of DISH on neuroimaging characteristics and postoperative prognosis of patients with thoracic myelopathy has not been established. Therefore, this study aimed to shed light on this issue. Methods: A monocentric study enrolled 167 eligible patients with thoracic ossification of ligamentum flavum (TOLF), who were followed up for at least 2 years. Clinico-radiological parameters and surgical outcomes were compared between the DISH+ and DISH− groups before and after propensity matching. Subgroup analysis was conducted to compare the functional outcomes between mild DISH (M-DISH) and moderately severe DISH (MS-DISH) groups. Results: Fifty-eight patients were diagnosed as DISH, and its prevalence was 34.7%. Patients with DISH presented with older age, more males, taller stature, heavier weight, more commonly diffuse-type TOLF (p < 0.05). The DISH group showed significantly worse recovery rate (RR) at the final follow-up before and after propensity matching (p < 0.01), and slightly lower preoperative VAS, higher postoperative VAS and lower VAS reduction, despite not reaching the significant differences. Subgroup analysis demonstrated that the M-DISH group was associated with the lower mJOA score (p = 0.01) and RR at the final follow-up (p = 0.001), and tended to present higher preoperative VAS than the MS-DISH group. Conclusions: DISH has a significant predisposition to the elderly males with diffuse-type TOLF. Although the presence of M-DISH might bring about a suboptimal surgical outcome, both DISH and non-DISH patients experienced good neurological function improvements and pain relief through thoracic posterior decompression.

Aims: Excessive manganese (Mn) exposure is toxic, and induces lipid deposition, but the underlying mechanisms remain elusive. Herein, we explored how dietary Mn supplementation affects lipid deposition and metabolism in the intestine of vertebrates using the yellow catfish Pelteobagrus fulvidraco as the model. Results: High-Mn (H-Mn) diet increased intestinal Mn content, promoted lipid accumulation and lipogenesis, and inhibited lipolysis. In addition, it induced oxidative stress, upregulated metal-response element-binding transcription factor-1 (MTF-1), and peroxisome proliferator-activated receptor gamma (PPARγ) protein expression in the nucleus, induced PPARγ acetylation, and the interaction between PPARγ and retinoid X receptor alpha (RXRα), while it downregulated sirtuin 1 (SIRT1) expression and activity. Mechanistically, Mn activated the MTF-1/divalent metal transporter 1 (DMT1) pathway, increased Mn accumulation in the mitochondria, and induced oxidative stress. This in turn promoted lipid deposition via deacetylation of PPARγ at K339 by SIRT1. Subsequently, PPARγ mediated Mn-induced lipid accumulation through transcriptionally activating fatty acid translocase, stearoyl-CoA desaturase 1, and perilipin 2 promoters. Innovation: These studies uncover a previously unknown mechanism by which Mn induces lipid deposition in the intestine via the oxidative stress-SIRT1-PPARγ pathway. Conclusion: High dietary Mn intake activates MTF-1/DMT1 and oxidative stress pathways. Oxidative stress-mediated PPARγ deacetylation at K339 site contributes to increased lipid accumulation. Our results provided a direct link between Mn and lipid metabolism via the oxidative stress-SIRT1-PPARγ axis. Antioxid. Redox Signal. 37, 417-436.

Iron is an essential micro-element, involved in multiple biological activities in vertebrates. Excess iron accumulation has been identified as an important mediator of lipid deposition. However, the underlying mechanisms remain unknown. In the present study, we found that a high-iron diet significantly increased intestinal iron content and upregulated the mRNA expression of two iron transporters (zip14 and fpn1). Intestinal iron overload increased lipogenesis, reduced lipolysis and promoted oxidative stress and mitochondrial dysfunction. Iron-induced lipid accumulation was mediated by hypoxia-inducible factor-1 α (HIF1α), which was induced in response to mitochondrial oxidative stress following inhibition of prolyl hydroxylase 2 (PHD2). Mechanistically, iron promoted lipid deposition by enhancing the DNA binding capacity of HIF1α to the pparγ and fas promoters. Our results provide experimental evidence that oxidative stress, mitochondrial dysfunction and the HIF1α-PPARγ pathway are critical mediators of iron-induced lipid deposition.