FBL Promotes LPS-Induced Neuroinflammation by Activating the NF-κB Signaling Pathway.

Purpose: Neuroinflammation occurs in response to central nervous system (CNS) injury, infection, stimulation by toxins, or autoimmunity. We previously analyzed the downstream molecular changes in HT22 cells (mouse hippocampal neurons) upon lipopolysaccharide (LPS) stimulation. We detected elevated expression of Fibrillarin (FBL), a nucleolar methyltransferase, but the associated proinflammatory mechanism was not systematically elucidated. The aim of this study was to investigate the underlying mechanisms by which FBL affects neuroinflammation. Methods: RT-real-time PCR, Western blotting and immunofluorescence were used to assess the mRNA and protein expression of FBL in HT22 cells stimulated with LPS, as well as the cellular localization and fluorescence intensity of FBL. BAY-293 (a son of sevenless homolog 1 (SOS1) inhibitor), SR11302 (an activator protein-1 (AP-1) inhibitor) and KRA-533 (a KRAS agonist) were used to determine the molecular mechanisms underlying the effect of FBL. AP-1 was predicted to be the target protein of FBL by molecular docking analysis, and validation was performed with T-5224 (an AP-1 inhibitor). In addition, the downstream signaling pathways of FBL were identified by transcriptome sequencing and verified by RT-real-time PCR. Results: LPS induced FBL mRNA and protein expression in HT22 cells. In-depth mechanistic studies revealed that when we inhibited c-Fos, AP-1, and SOS1, FBL expression decreased, whereas FBL expression increased when KRAS agonists were used. In addition, the transcript levels of inflammatory genes in the NF-kB signaling pathway (including CD14, MYD88, TNF, TRADD, and NFKB1) were elevated after the overexpression of FBL. Conclusion: LPS induced the expression of FBL in HT22 cells through the RAS/MAPK signaling pathway, and FBL further activated the NF-kB signaling pathway, which promoted the expression of relevant inflammatory genes and the release of cytokines. The present study reveals the mechanism by which FBL promotes neuroinflammation and offers a potential target for the treatment of neuroinflammation.

CRISPR screens in mechanism and target discovery for AML.

CRISPR-based screens have discovered novel functional genes involving in diverse tumor biology and elucidated the mechanisms of the cancer pathological states. Recently, with its randomness and unbiasedness, CRISPR screens have been used to discover effector genes with previously unknown roles for AML. Those novel targets are related to AML survival resembled cellular pathways mediating epigenetics, synthetic lethality, transcriptional regulation, mitochondrial and energy metabolism. Other genes that are crucial for pharmaceutical targeting and drug resistance have also been identified. With the rapid development of novel strategies, such as barcodes and multiplexed mosaic CRISPR perturbation, more potential therapeutic targets and mechanism in AML will be discovered. In this review, we present an overview of recent progresses in the development of CRISPR-based screens for the mechanism and target identification in AML and discuss the challenges and possible solutions in this rapidly growing field.

Bispecific CAR T cell therapy targeting BCMA and CD19 in relapsed/refractory multiple myeloma: a phase I/II trial.

Despite the high therapeutic response achieved with B-cell maturation antigen (BCMA)-specific chimeric antigen receptor (CAR) T-cell therapy in relapsed and refractory multiple myeloma (R/R MM), primary resistance and relapse exist with single-target immunotherapy. Here, we design bispecific BC19 CAR T cells targeting BCMA/CD19 and evaluate antimyeloma activity in vitro and in vivo. Preclinical results indicate that BC19 CAR specifically recognize target antigens, and BC19 CAR T cells mediate selective killing of BCMA or CD19-positive cancer cells. BC19 CAR T cells also exhibit potent antigen-specific anti-tumor activity in xenograft mouse models. We conduct an open-label, single-arm, phase I/II study of BC19 CAR T cells in 50 patients with R/R MM (ChiCTR2000033567). The primary endpoint was safety. BC19 CAR T cells are well tolerated with grade 3 or higher cytokine release syndrome in 8% of patients and grade 1 neurotoxic events in 4% of patients, which meet the pre-specified primary endpoint. Secondary endpoints include overall response rate (92%), median progression-free survival (19.7 months), median overall survival (19.7 months) and median duration of response (not reached). Our study demonstrates that bispecific BC19 CAR T cells are feasible, safe and effective in treating patients with R/R MM.

π-Extended Nonfullerene Acceptor for Compressed Molecular Packing in Organic Solar Cells To Achieve over 20% Efficiency.

Organic photovoltaics (OPVs) suffer from a trade-off between efficient charge transport and suppressed nonradiative recombination due to the aggregation-induced luminance quenching of organic semiconductors. To resolve this grand challenge, a π-extended nonfullerene acceptor (NFA) B6Cl with large voids among the honeycomb network is designed and introduced into photovoltaic systems. We find that the presence of a small amount of (i.e., 0.5 or 1 wt %) B6Cl can compress the molecular packing of the host acceptor L8-BO, leading to shortened π-π stacking distance from 3.59 to 3.50 Å (that will improve charge transport) together with ordered alkyl chain packing (that will inhibit nonradiative energy loss due to the suppressed C-C and C-H bonds vibrations), as validated by high-energy X-ray scattering measurements. This morphology transformation ultimately results in simultaneously improved JSC, FF, and VOC of OPVs. As a result, the maximum PCEs of PM6:L8-BO and D18:L8-BO are increased from 19.1 and 19.3% to 19.8 and 20.2%, respectively, which are among the highest values for single-junction OPVs. The university of B6Cl to increase the performance of OPVs is further evidenced in a range of polymer:NFA OPVs.

Fully-Automatic Detection and Diagnosis System for Thyroid Nodules Based on Ultrasound Video Sequences by Artificial Intelligence.

Background: Interpretation of ultrasound findings of thyroid nodules is subjective and labor-intensive for radiologists. Artificial intelligence (AI) is a relatively objective and efficient technology. We aimed to establish a fully automatic detection and diagnosis system for thyroid nodules based on AI technology by analyzing ultrasound video sequences. Patients and Methods: We prospectively acquired dynamic ultrasound videos of 1067 thyroid nodules (804 for training and 263 for validation) from December 2018 to January 2021. All the patients underwent hemithyroidectomy or total thyroidectomy. Dynamic ultrasound videos were used to develop an AI system consisting of two deep learning models that could automatically detect and diagnose thyroid nodules. Average precision (AP) was used to estimate the performance of the detection model. The area under the receiver operating characteristic curve (AUC) was used to measure the performance of the diagnostic model. Results: Location and shape were accurately detected with a high AP of 0.914 in the validation cohort. The AUC of the diagnostic model was 0.953 in the validation cohort. The sensitivity and specificity of junior and senior radiologists were 76.9% vs 78.3% and 68.4% vs 81.1%, respectively. The diagnostic performance of the AI diagnostic model was superior to that of junior radiologists (P = 0.016) and was not significantly different from that of senior radiologists (P = 0.281). Conclusion: We established a fully automatic detection and diagnosis system for thyroid nodules based on ultrasound video using an AI approach that can be conveniently applied to optimize the management of patients with thyroid nodules.

Mussel shell-derived pro-regenerative scaffold with conductive porous multi-scale-patterned microenvironment for spinal cord injury repair.

It is well-established that multi-scale porous scaffolds can guide axonal growth and facilitate functional restoration after spinal cord injury (SCI). In this study, we developed a novel mussel shell-inspired conductive scaffold for SCI repair with ease of production, multi-scale porous structure, high flexibility, and excellent biocompatibility. By utilizing the reducing properties of polydopamine, non-conductive graphene oxide (GO) was converted into conductive reduced graphene oxide (rGO) and crosslinked in situ within the mussel shells. In vitro experiments confirmed that this multi-scale porous Shell@PDA-GO could serve as structural cues for enhancing cell adhesion, differentiation, and maturation, as well as promoting the electrophysiological development of hippocampal neurons. After transplantation at the injury sites, the Shell@PDA-GO provided a pro-regenerative microenvironment, promoting endogenous neurogenesis, triggering neovascularization, and relieving glial fibrosis formation. Interestingly, the Shell@PDA-GO could induce the release of endogenous growth factors (NGF and NT-3), resulting in the complete regeneration of nerve fibers at 12 weeks. This work provides a feasible strategy for the exploration of conductive multi-scale patterned scaffold to repair SCI.

Lung adenocarcinoma patients with ROS1-rearranged tumors by sex and smoking intensity.

Background: ROS1 rearrangements (ROS1+) define a distinct molecular subset of lung adenocarcinomas. ROS1 + tumors are known to occur more in never-smokers, but the frequency and outcome of ROS1 positivity by sex and smoking intensity are not clearly documented. Patients and methods: This patient cohort study included all never- (<100 cigarettes lifetime) and light- (100 cigarettes-20 pack-years) smokers, and a sample of heavy-smokers. ROS1 + rates by sex and smoking intensity were compared within and beyond our study. Survival outcomes were analyzed using Kaplan-Meier curves and Cox proportional hazards models. Results: Of the 571 total patients, ROS1 + was detected in 24 (4.2%): 6.4% in men and 3.0% in women; 5.1% in never-, 5.7% in light-, and 1.8% in heavy-smokers (P=0.05). Among the 209 stage IIIB-IV patients, men had much higher ROS1 + rate (11.1%) not only than women (1.7%, P=0.004) in our study, but also than men (0.4%-1.8%) in 8 published studies (Ps = 0.0019-0.0001). ROS1+ rates were similar between never- (9.3%) and light-smokers (8.1%) and significantly lower in heavy-smokers (1.2%, P=0.017), a finding confirmed by 6 published studies (Ps = 0.041-0.0001). Overall survival of ROS1 + patients were significantly better than the ROS1- (P=0.023) mainly due to targeted therapy. Among patients who exhibited resistance to crizotinib, follow-up treatment of entrectinib and lorlatinib showed remarkable survival benefits. Conclusions: The ROS1 + rates were higher in men than in women, and similar in never- and light-smokers, more pronounced in stage IIIB-IV patients. Newer-generation ALK/ROS1-targeted drugs showed efficacy in a cohort of crizotinib resistant ROS1 + patients. These results, when validated, could assist efficiently accruing ROS1 + patients.

Effects of Mesenchymal Stem Cells-Derived Extracellular Vesicles on Inhibition of Hepatic Fibrosis by Delivering miR-200a.

BACKGROUND: Hepatic fibrosis (HF) is a common pathological feature of chronic hepatic diseases. We aimed to illuminate the significance of amniotic mesenchymal stem cells (AMSCs)-derived extracellular vesicles (AMSCs-EVs) in HF. METHODS: Human AMSCs-EVs were isolated and identified. HF mice were constructed and treated with EVs. The fibrosis was observed by staining experiments and Western blot (WB) assay. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and hepatic hydroxyproline (Hyp) were detected to confirm liver function. For the in vitro experiments, human hepatic stellate cells were induced with transforming growth factor-ß and treated with EVs. To measure the degree of HF, the expression of alpha-smooth muscle actin (α-SMA) and Collagen I was detected by WB assay, and cell proliferation was detected by cell counting kit 8 assay. The levels of miR-200a, Zinc finger E-box binding homeobox 1 (ZEB1), and phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3) were detected by WB and real-time quantitative polymerase chain reaction. The binding of ZEB1 to PIK3R3 and miR-200a to ZEB1 was analyzed by chromatin immunoprecipitation and dual luciferase assays to validate their relationships. RESULTS: Human AMSCs and AMSCs-EVs were obtained. Serum ALT, AST, TBIL, and hepatic Hyp were increased, implying the fibrosis degree was aggravated in HF mice, which was decreased again after EV treatment. EVs inhibited HF degree by reducing α-SMA and Collagen I and promoting cell proliferation. AMSCs-EVs delivered miR-200a into hepatocytes, which up-regulated miR-200a expression, inhibited ZEB1 expression, and reduced its enrichment on the PIK3R3 promoter, therefore inhibiting PIK3R3 expression and alleviating HF. Overexpression of ZEB1 or PIK3R3 attenuated the anti-fibrotic effect of AMSCs-EVs. CONCLUSION: Human AMSCs-derived EVs mediated miR-200a delivery and inhibition of intracellular ZEB1/PIK3R3 axis to exert anti-fibrosis effects.

Unveiling the methionine cycle: a key metabolic signature and NR4A2 as a methionine-responsive oncogene in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a deadly malignancy with notable metabolic reprogramming, yet the pivotal metabolic feature driving ESCC progression remains elusive. Here, we show that methionine cycle exhibits robust activation in ESCC and is reversely associated with patient survival. ESCC cells readily harness exogenous methionine to generate S-adenosyl-methionine (SAM), thus promoting cell proliferation. Mechanistically, methionine augments METTL3-mediated RNA m6A methylation through SAM and revises gene expression. Integrative omics analysis highlights the potent influence of methionine/SAM on NR4A2 expression in a tumor-specific manner, mediated by the IGF2BP2-dependent stabilization of methylated NR4A2 mRNA. We demonstrate that NR4A2 facilitates ESCC growth and negatively impacts patient survival. We further identify celecoxib as an effective inhibitor of NR4A2, offering promise as a new anti-ESCC agent. In summary, our findings underscore the active methionine cycle as a critical metabolic characteristic in ESCC, and pinpoint NR4A2 as a novel methionine-responsive oncogene, thereby presenting a compelling target potentially superior to methionine restriction.

Association of pretreatment neutrophil-to-lymphocyte ratio with clinical outcomes in cancer immunotherapy: An evidence synthesis from 30 meta-analyses.

BACKGROUND: The Neutrophil-to-lymphocyte ratio (NLR) holds relevance in cancer immunotherapy outcomes, yet its validation remains limited. Thus, we conducted an umbrella review to comprehensively assess the association between pretreatment NLR and immunotherapy outcomes, along with evaluating their credibility and strength. METHODS: Electronic databases, including PubMed, Web of Science, Embase, Scopus, and Cochrane, were systematically searched for eligible systematic reviews and meta-analyses. Quality assessment and evidence grading utilized AMSTAR, GRADE, and additional classification criteria, following PRISMA and PRIOR guidelines. RESULTS: Thirty unique meta-analyses were included, with 24 associations (80%) exhibiting statistical significance. Notably, associations between pretreatment NLR and the prognosis of renal cell carcinoma, hepatocellular carcinoma, melanoma, and non-small cell lung cancer garnered highly suggestive or convincing evidence grading. CONCLUSIONS: Elevated pretreatment NLR correlates with poor outcomes in cancer immunotherapy, suggesting its potential as a biomarker for identifying appropriate treatment populations and predicting clinical outcomes. Nevertheless, further validation through prospective cohort studies is warranted.

Rosai-Dorfman disease manifesting as a solitary mass with fat in the thymus a case report.

BACKGROUND: Sinus histiocytosis with massive lymphadenopathy, also known as Rosai-Dorfman disease, is a rare, self-limiting disease that predominantly affects children and young adults. Moreover, the disease is characterized by painless bilateral cervical lymphadenopathy in 95% of the patients. However, few reports are available on the Rosai-Dorfman disease of the thymus. CASE PRESENTATION: We report a rare case of thymic Rosai-Dorfman disease detected using computed tomography. During a medical examination, a 50-year-old man underwent a chest computed tomography scan, which revealed an anterior mediastinal single mass with fat in the thymus. A thymectomy was performed to completely remove the tumor using a thoracoscopic technique due to a clinical suspicion of thymoma. Furthermore, Rosai-Dorfman disease was confirmed using histological and immunohistochemical analyses. CONCLUSIONS: To the best of our knowledge, this is the sixth case of thymus-affecting solitary Rosai-Dorfman disease with histological and immunohistochemical evidence. Fat in the thymus, as was present in this case, has never been described in Rosai-Dorfman disease previously. Our results highlight the challenge of diagnosing this uncommon tumor before surgery, and more cases need to be reported to help with the preoperative diagnosis of such a rare tumor.

Crosslinking-induced patterning of MOFs by direct photo- and electron-beam lithography.

Metal-organic frameworks (MOFs) with diverse chemistry, structures, and properties have emerged as appealing materials for miniaturized solid-state devices. The incorporation of MOF films in these devices, such as the integrated microelectronics and nanophotonics, requires robust patterning methods. However, existing MOF patterning methods suffer from some combinations of limited material adaptability, compromised patterning resolution and scalability, and degraded properties. Here we report a universal, crosslinking-induced patterning approach for various MOFs, termed as CLIP-MOF. Via resist-free, direct photo- and electron-beam (e-beam) lithography, the ligand crosslinking chemistry leads to drastically reduced solubility of colloidal MOFs, permitting selective removal of unexposed MOF films with developer solvents. This enables scalable, micro-/nanoscale (≈70 nm resolution), and multimaterial patterning of MOFs on large-area, rigid or flexible substrates. Patterned MOF films preserve their crystallinity, porosity, and other properties tailored for targeted applications, such as diffractive gas sensors and electrochromic pixels. The combined features of CLIP-MOF create more possibilities in the system-level integration of MOFs in various electronic, photonic, and biomedical devices.

Ethylene induced AcNAC3 and AcNAC4 take part in ethylene synthesis through mediating AcACO1 during kiwifruit (Actinidia chinensis) ripening.

BACKGROUND: Ethylene plays a vital role in the ripening process of kiwifruit. A terrific amount of transcription factors (TFs) have been shown to regulate ethylene synthesis in various fruits. RESULTS: In this research, two new NAC TFs, named AcNAC3 and AcNAC4, were isolated from kiwifruit, which belonged to NAM subfamily. Bioinformatics analysis showed that both AcNAC3 and AcNAC4 were hydrophilic proteins with similar three-dimensional structures. The expression levels of AcNAC3, AcNAC4 and AcACO1 increased during kiwifruit ripening, as well as were induced by ethylene and repressed by 1-MCP. Correlation analysis exhibited that ethylene production was positively correlated with the expression levels of AcNAC3, AcNAC4 and AcACO1. Moreover, both AcNAC3 and AcNAC4 acted as transcriptional activators and could bind to and activate AcACO1 promoter. CONCLUSION: All results unveiled that the ethylene-induced AcNAC3 and AcNAC4 were transcriptional activators, and might participate in kiwifruit ripening and ethylene biosynthesis through activating AcACO1, providing a new insight of ethylene synthetic regulation during kiwifruit ripening. This article is protected by copyright. All rights reserved.

Construction of yield loss indicators for cold vortex, light-temperature-water combined stress during the flowering period of rice in Northeast China.

The construction of a yield loss evaluation index for the cold vortex type light-temperature-water composite adversity during rice flowering period in Northeast China is important for elucidating the impacts of cold vortex type composite disasters on rice yield loss in middle and high latitude areas. Moreover, it can provide meteorological support to ensure safe production of high-quality japonica rice in China and contribute to regional disaster reduction and efficiency improvement. By combining growth period data, meteorological data, and yield data, we delineated and constructed the composite stress occurrence index of cold vortex type light-temperature-water at the flowering stage of japonica. We analyzed the relationship between factors causing disasters and yield structure, as well as the relationship between different yield structures and yield by employing BP neural network method. We further dissected the processes involved in the causation of combined disasters. Based on the K-means clustering method and historical typical disaster years, we quantified the critical thresholds and disaster grades, and established an evaluation index and model for assessing yield loss caused by combined stress from cold vortex type light-temperature-water. Finally, we examined the spatial and temporal variations of low temperature, abundant rainfall, and reduced sunlight during the flowering period in the three provinces of Northeast China. Results showed that the critical thresholds for light, temperature, and water stress index during the flowering stage of mild, moderate, and severe cold vortex types were [0, 0.21), [0.21, 0.32), and [0.32, 0.64], respectively. The rates of yield loss were [0, 0.03), [0.03, 0.08), and [0.08, 0.096], respectively. Based on the verification results of a total of 751 samples in 11 random years from 1961 to 2020, the percentage of stations for which the production reduction grade, as calculated by the composite index developed in this study, aligning with the actual production reduction grade was 63.7%, consistently exceeding 58.0% annually. Moreover, the proportion of sites with a similarity or difference level of 1 stood at 88.3%, surpassing 85.0% in each year. The index could effectively assess the extent of rice yield loss caused by cold vortex disasters in Northeast China.

Photothermal Synergic Cross-Linking Hole Transport Layer for Highly Efficient RGB QLEDs.

Developing an insoluble cross-linkable hole transport layer (HTL) plays an important role for solution-processed quantum dots light-emitting diodes (QLEDs) to fabricate a multilayer device with separated quantum dots layers and HTLs. In this work, a facile photothermal synergic cross-linking strategy is simultaneous annealing and UV irradiation to form the high-quality cross-linked film as the HTL without any photoinitiator, which efficiently reduces the cross-linking temperature to the low temperature of 130 °C and enhances the hole mobility of the 3-vinyl-9-{4-[4-(3-vinylcarbazol-9-yl)phenyl]phenyl}carbazole (CBP-V) thin films. The obtained high-quality cross-linked CBP-V films exhibited smooth morphology, excellent solvent resistance, and high mobility. Moreover, the high-performance red, green, and blue (RGB) QLEDs are successfully fabricated by using the photothermal synergic cross-linked HTLs, which achieved the maximum external quantum efficiency of 25.69, 24.42, and 16.51%, respectively. This work presents a strategy of using the photothermal synergic cross-linked HTLs for fabrication of high-performance QLEDs and advancing their related device applications.

Lentinus edodes mycelium polysaccharide inhibits AGEs-induced HUVECs pyroptosis by regulating LncRNA MALAT1/miR-199b/mTOR axis and NLRP3/Caspase-1/GSDMD pathway.

A novel Lentinus edodes mycelia polysaccharide (LMP) prepared in our laboratory has been identified to be effective in inhibiting the damage of islet ß cells induced by glucose toxicity. However, whether it can effectively alleviate the pyroptosis of human umbilical vein endothelial cells (HUVECs) induced by advanced glycation end products (AGEs) remains unclear. Bioinformatics and cell biology techniques were used to explore the mechanism of LMP inhibiting AGEs-induced HUVECs damage. The results indicated that AGEs significantly increased the expression of LncRNA MALAT1, decreased cell viability to 79.67 %, increased intracellular ROS level to 248.19 % compared with the control group, which further led to cell membrane rupture. The release of LDH in cellular supernatant was increased to 149.42 %, and the rate of propidium iodide staining positive cells increased to 277.19 %, indicating the cell pyroptosis occurred. However, the above trend was effectively retrieved after the treatment with LMP. LMP effectively decreased the expression of LncRNA MALAT1 and mTOR, promoted the expression of miR-199b, inhibited AGEs-induced HUVECs pyroptosis by regulating the NLRP3/Caspase-1/GSDMD pathway. LncRNA MALAT1 might be a new target for LMP to inhibit AGEs-induced HUVECs pyroptosis. This study manifested the role of LMP in improving diabetes angiopathy and broadens the application of polysaccharide.

Protein Engineering of a Novel ß-Galactosidase from Thermus scotoductus for Efficient Synthesis of Lacto-N-Neotetraose from Chitin Powder.

A novel ß-galactosidase (TsGal48) from Thermus scotoductus was cloned, and the enzyme was biochemically characterized. TsGal48 catalyzed the synthesis of lacto-N-neotetraose (LNnT) from lactose via the transglycosylation reaction with a maximal yield of 20%, which is the highest yield for the synthesis of LNnT so far. To further improve the yield of LNnT, TsGal48 was successfully engineered by directed evolution and site-saturation mutagenesis. A mutated ß-galactosidase (mTsGal48) was selected and characterized. mTsGal48 produced LNnT with a yield of 27.7 g/L, which is 1.4-fold higher than that of TsGal48 (19.7 g/L). Then, a developed strategy for LNnT synthesis from chitin powder was provided in a 30 L bioreactor. The reaction process included chitin powder hydrolysis, lacto-N-triose II (LNT2) synthesis, and LNnT synthesis. The reaction time was reduced from 44 to 17 h in chitin powder hydrolysis and LNT2 synthesis. The content of LNnT was up to 25 g/L in the multienzyme system. The green and efficient route may be suitable for large-scale production of LNnT from chitin powder.

The mechanisms of mitochondrial abnormalities that contribute to sleep disorders and related neurodegenerative diseases.

Sleep is a highly intricate biological phenomenon, and its disorders play a pivotal role in numerous diseases. However, the specific regulatory mechanisms remain elusive. In recent years, the role of mitochondria in sleep disorders has gained considerable attention. Sleep deprivation not only impairs mitochondrial morphology but also decreases the number of mitochondria and triggers mitochondrial dysfunction. Furthermore, mitochondrial dysfunction has been implicated in the onset and progression of various sleep disorder-related neurological diseases, especially neurodegenerative conditions. Therefore, a greater understanding of the impact of sleep disorders on mitochondrial dysfunction may reveal new therapeutic targets for neurodegenerative diseases. In this review, we comprehensively summarize the recent key findings on the mechanisms underlying mitochondrial dysfunction caused by sleep disorders and their role in initiating or exacerbating common neurodegenerative diseases. In addition, we provide fresh insights into the diagnosis and treatment of sleep disorder-related diseases.