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Familial hypercholesterolemia (FH) is one of the most prevalent monogenetic disorders leading to cardiovascular disease (CVD) worldwide. Mutations in Ldlr, encoding a membrane-spanning protein, account for the majority of FH cases. No effective and safe clinical treatments are available for FH. Adenine base editor (ABE)-mediated molecular therapy is a promising therapeutic strategy to treat genetic diseases caused by point mutations, with evidence of successful treatment in mouse disease models. However, due to the differences in the genomes between mice and humans, ABE with specific sgRNA, a key gene correction component, cannot be directly used to treat FH patients. Thus, we generated a knock-in mouse model harboring the partial patient-specific fragment and including the Ldlr W490X mutation. LdlrW490X/W490X mice recapitulated cholesterol metabolic disorder and clinical manifestations of atherosclerosis associated with FH patients, including high plasma low-density lipoprotein cholesterol levels and lipid deposition in aortic vessels. Additionally, we showed that the mutant Ldlr gene could be repaired using ABE with the cellular model. Taken together, these results pave the way for ABE-mediated molecular therapy for FH.
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Hipercolesterolemia , Hiperlipoproteinemia Tipo II , Humanos , Ratones , Animales , ARN Guía de Sistemas CRISPR-Cas , Hiperlipoproteinemia Tipo II/genética , Hiperlipoproteinemia Tipo II/terapia , Mutación , Hipercolesterolemia/genética , Colesterol , Receptores de LDL/genética , Receptores de LDL/metabolismoRESUMEN
CRISPR-Cas9 is a versatile gene editing tool with a broad application of basic research and clinical therapeutics. However, the potential impact caused by off-target effects remains a critical bottleneck. The small Cas9 ortholog from Staphylococcus auricularis (SauriCas9) was identified, which recognizes a 5'-NNGG-3' protospacer adjacent motif (PAM), exhibiting high activity for genome editing. Recently, we also reported enhanced-fidelity Staphylococcus aureus Cas9 (efSaCas9), which harbors a single mutation N260D. Protein sequence alignment revealed that SauriCas9 has 62.4% sequence identity with SaCas9. Because SauriCas9 is more flexible in recognizing the target sequence with PAM of 5'-NNGG-3' than SaCas9 of 5'-NNGRRT-3' PAM, we sought to test whether key mutation(N260D) or adjacent residue mutation in efSaCas9 can be appliable to SauriCas9. With this concept, two engineered SauriCas9 variants (SauriCas9-HF1, harboring the N269D mutation; SauriCas9-HF2, harboring the D270N mutation) dramatically improved targeting specificity by targeted deep sequencing and GUIDE-seq. At certain sites, reduced off-target effects (approximately 61.6- and 111.9-fold improvements) of SauriCas9-HF2 compared with wild-type SauriCas9 were observed. Overall, two identified SauriCas9 variants (SauriCas9-HF1 and SauriCas9-HF2) expand the utility of the CRISPR toolkit for research and therapeutic applications.
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Sistemas CRISPR-Cas , Infecciones Estafilocócicas , Humanos , Staphylococcus/genética , Staphylococcus aureus/genéticaRESUMEN
Electrochemical acetylene reduction (EAR) employing Cu catalysts represents an environmentally friendly and cost-effective method for ethylene production and purification. However, Cu-based catalysts encounter product selectivity issues stemming from carbon-carbon coupling and other side reactions. We explored the use of secondary metals to modify Cu-based catalysts and identified Cd decoration as particular effective. Cd decoration demonstrated a high ethylene Faradaic efficiency (FE) of 98.38 % with well-inhibited carbon-carbon coupling reactions (0.06 % for butadiene FE at -0.5â V versus reversible hydrogen electrode) in a 5â vol % acetylene gas feed. Notably, ethylene selectivity of 99.99 % was achieved in the crude ethylene feed during prolonged stability tests. Theoretical calculations revealed that Cd metal accelerates the water dissociation on neighboring Cu surfaces allowing more H* to participate in the acetylene semi-hydrogenation, while increasing the energy barrier for carbon-carbon coupling, thereby contributing to a high ethylene semi-hydrogenation efficiency and significant inhibition of carbon-carbon coupling. This study provides a paradigm for a deeper understanding of secondary metals in regulating the product selectivity of EAR electrocatalysts.
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Pain, as one of the most prevalent clinical symptoms, is a complex physiological and psychological activity. Long-term severe pain can become unbearable to the body. However, existing treatments do not provide satisfactory results. Therefore, new mechanisms and therapeutic targets need to be urgently explored for pain management. The Sonic hedgehog (Shh) signaling pathway is crucial in embryonic development, cell differentiation and proliferation, and nervous system regulation. Here, we review the recent studies on the Shh signaling pathway and its action in multiple pain-related diseases. The Shh signaling pathway is dysregulated under various pain conditions, such as pancreatic cancer pain, bone cancer pain, chronic post-thoracotomy pain, pain caused by degenerative lumbar disc disease, and toothache. Further studies on the Shh signaling pathway may provide new therapeutic options for pain patients.
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Dolor en Cáncer , Neoplasias Pancreáticas , Humanos , Proteínas Hedgehog/metabolismo , Transducción de Señal/fisiología , Neoplasias Pancreáticas/metabolismo , Diferenciación CelularRESUMEN
OBJECTIVES: Niclosamide is commonly used as an antiparasitic drug in veterinary clinics. The objectives of this study were to evaluate the efficacy of niclosamide against resistant Gram-positive bacteria in vitro and in an in vivo experimental model of topical bacterial infection. Moreover, to study the antibacterial mechanism of niclosamide to Staphylococcus aureus. METHODS: A mouse topical infection model was established to detect the antibacterial activity of niclosamide in vivo. The antimicrobial mechanism was probed by visualizing the bacterial morphologies using scanning electron microscopy and transmission electron microscopy. Moreover, the haemolytic assay and western blotting analysis were performed to evaluate whether niclosamide could inhibit the secretion of alpha-haemolysin (α-HL) from S. aureus. RESULTS: The MICs of niclosamide were below 0.5â mg/L for Gram-positive bacteria, showing excellent antibacterial activity in vitro. The in vivo antibacterial activity results indicated that niclosamide treatment at 10â mg/kg of body weight caused a significant reduction in the abscess area and the number of S. aureus cells. Moreover, the antibacterial mechanism of niclosamide showed that the surface morphology of S. aureus displayed noticeable shrinkage, with an increasing number of small vacuole-like structures observed as the drug concentration increased. Intracellular ATP levels were found to decrease in a niclosamide dose-dependent manner. Haemolysis and western blotting analyses revealed that niclosamide inhibited the haemolytic activity of S. aureus by inhibiting α-HL expression under subinhibitory concentration conditions. CONCLUSIONS: Niclosamide has significant potential for development into drugs that prevent and treat diseases caused by Gram-positive bacteria such as Staphylococcus and Streptococcus.
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Reposicionamiento de Medicamentos , Infecciones por Bacterias Grampositivas , Niclosamida , Animales , Ratones , Antibacterianos/farmacología , Bacterias Grampositivas/efectos de los fármacos , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Infecciones por Bacterias Grampositivas/microbiología , Pruebas de Sensibilidad Microbiana , Niclosamida/farmacología , Staphylococcus aureus/efectos de los fármacos , Resultado del Tratamiento , Modelos Animales de EnfermedadRESUMEN
Developing efficient and stable Pt-based oxygen reduction reaction (ORR) catalysts is a way to promote the large-scale application of fuel cells. Pt-based alloy nanowires are promising ORR catalysts, but their application is hampered by activity loss caused by structural destruction during long-term cycling. Herein, the preparation of ordered PtFeIr intermetallic nanowire catalysts with an average diameter of 2.6â nm and face-centered tetragonal structure (fct-PtFeIr/C) is reported. A silica-protected strategy prevents the deformation of PtFeIr nanowires during the phase transition at high temperature. The as-prepared fct-PtFeIr/C exhibited superior mass activity for ORR (2.03â A mgPt -1 ) than disordered PtFeIr nanowires with face-centered cubic structure (1.11â A mgPt -1 ) and commercial Pt/C (0.21â A mgPt -1 ). Importantly, the structure and electrochemical performance of fct-PtFeIr/C were maintained after stability tests, showing the advantages of the ordered structure.
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Candida albicans, an opportunistic fungus, causes dental caries and contributes to mucosal bacterial dysbiosis leading to a second infection. Furthermore, C.albicans forms biofilms that are resistant to medicinal treatment. To make matters worse, antifungal resistance has spread (albeit slowly) in this species. Thus, it has been imperative to develop novel, antifungal drug compounds. Herein, a peptide was engineered with the sequence of RRFSFWFSFRR-NH2; this was named P19. This novel peptide has been observed to exert disruptive effects on fungal cell membrane physiology. Our results showed that P19 displayed high binding affinity to lipopolysaccharides (LPS), lipoteichoic acids (LTA) and the plasma membrane phosphatidylinositol (PI), phosphatidylserine (PS), cardiolipin, and phosphatidylglycerol (PG), further indicating that the molecular mechanism of P19 was not associated with the receptor recognition, but rather related to competitive interaction with the plasma membrane. In addition, compared with fluconazole and amphotericin B, P19 has been shown to have a lower potential for resistance selection than established antifungal agents.
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Antifúngicos/farmacología , Biopelículas/efectos de los fármacos , Candida albicans/efectos de los fármacos , Oligopéptidos/farmacología , Antifúngicos/química , Candida albicans/fisiología , Cardiolipinas/metabolismo , Membrana Celular/efectos de los fármacos , Lipopolisacáridos/metabolismo , Oligopéptidos/química , Fosfatidilgliceroles/metabolismo , Fosfatidilinositoles/metabolismo , Fosfatidilserinas/metabolismo , Ácidos Teicoicos/metabolismo , Triptófano/químicaRESUMEN
NiFe-layered double hydroxides (NiFe-LDH) are among the most active catalysts developed to date for the oxygen evolution reaction (OER) in alkaline media, though their long-term OER stability remains unsatisfactory. Herein, we reveal that the stability degradation of NiFe-LDH catalysts during alkaline OER results from a decreased number of active sites and undesirable phase segregation to form NiOOH and FeOOH, with metal dissolution underpinning both of these deactivation mechanisms. Further, we demonstrate that the introduction of cation-vacancies in the basal plane of NiFe LDH is an effective approach for achieving both high catalyst activity and stability during OER. The strengthened binding energy between the metals and oxygen in the LDH sheets, together with reduced lattice distortions, both realized by the rational introduction of cation vacancies, drastically mitigate metal dissolution from NiFe-LDH under high oxidation potentials, resulting in the improved long-term OER stability. In addition, the cation vacancies (especially M3+ vacancies) accelerate the evolution of surface γ-(NiFe)OOH phases, thereby boosting the OER activity. The present study highlights that tailoring atomic cation-vacancies is an important strategy for the development of active and stable OER electrocatalysts.
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The development of efficient and stable electrocatalysts for the oxygen reduction reaction (ORR) is critical for the large-scale production of fuel cells. Platinum (Pt) nanoparticle catalysts show excellent performance for ORR, though the high cost of Pt is a limiting factor that directly impacts fuel cell production costs. Alloying Pt with other transition metals is an effective strategy to reduce Pt utilization whilst maintaining good ORR performance. In this work, novel hollow PtFe alloy catalysts were successfully synthesized by high-temperature pyrolysis of SiO2 -coated Pt-Fe3 O4 nanoparticle dimers supported on carbon at 900 °C, followed by SiO2 shell removal and partial dealloying of the PtFe nanoparticles formed using HF. The obtained hollow PtFe nanoparticle catalysts (denoted herein as PtFe-900) showed a 2.3-fold enhancement in ORR mass activity compared to PtFe nanoparticles synthesized without SiO2 protection, and a remarkable 7.8-fold enhancement relative to a commercial Pt/C catalyst. Further, after 10 000â potential cycles, the ORR mass activity of PtFe-900 remained very high (90.9 % of the initial mass activity). The outstanding ORR performance of PtFe-900 can be attributed to the modification of Pt lattice and electronic structure by alloying with Fe at high temperature under the protection of the SiO2 coating. This work guides the development of improved, highly dispersed Pt-based alloy nanoparticle catalysts for ORR and fuel cell applications.
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BACKGROUND: This study explored the relationships between the low-/high-density lipoprotein cholesterol ratio (LDL-C/HDL-C) and other clinical indicators and ischaemic stroke (IS) in patients with non-valvular atrial fibrillation (NVAF) in Xinjiang. The findings could provide a theoretical and therapeutic basis for NVAF patients. METHODS: NVAF patients who were admitted to 10 medical centres across Xinjiang were divided into stroke (798 patients) and control (2671 patients) groups according to the occurrence of first acute IS. Univariate and multivariate logistic regression analysis were used to examine the independent risk factors for IS in NVAF patients. Factor analysis and principal component regression analysis were used to analyse the main factors influencing IS. Receiver operating characteristic (ROC) curve analysis was used to evaluate the discriminatory ability of LDL-C/HDL-C for predicting the occurrence of IS. RESULTS: The stroke group had an average age of 71.64 ± 9.96 years and included 305 females (38.22%). The control group had a mean age of 67.30 ± 12.01 years and included 825 females (30.89%). Multivariate logistic regression showed that the risk of IS in the highest LDL-C/HDL-C quartile (≥2.73) was 16.23-fold that of the lowest quartile (< 1.22); IS risk was 2.27-fold higher in obese patients than in normal-weight subjects; IS risk was 3.15-fold higher in smoking patients than in non-smoking patients. The area under the ROC curve of LDL-C/HDL-C was 0.76, the optimal critical value was 2.33, the sensitivity was 63.53%, and the specificity was 76.34%. Principal component regression analysis showed that LDL-C/HDL-C, age, smoking, drinking, LDL-C and hypertension were risk factors for IS in NVAF patients. CONCLUSIONS: LDL-C/HDL-C > 1.22, smoking, BMI ≥24 kg/m2 and CHA2DS2-VASc score were independent risk factors for IS in NVAF patients; LDL-C/HDL-C was the main risk factor.
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Fibrilación Atrial/epidemiología , Accidente Cerebrovascular Isquémico/epidemiología , Obesidad/epidemiología , Anciano , Fibrilación Atrial/sangre , Fibrilación Atrial/complicaciones , Fibrilación Atrial/patología , Estudios de Casos y Controles , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Femenino , Humanos , Accidente Cerebrovascular Isquémico/sangre , Accidente Cerebrovascular Isquémico/complicaciones , Accidente Cerebrovascular Isquémico/patología , Masculino , Obesidad/sangre , Obesidad/complicaciones , Obesidad/patología , Factores de RiesgoRESUMEN
Carbon-supported NiII single-atom catalysts with a tetradentate Ni-N2 O2 coordination formed by a Schiff base ligand-mediated pyrolysis strategy are presented. A NiII complex of the Schiff base ligand (R,R)-(-)-N,N'-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediamine was adsorbed onto a carbon black support, followed by pyrolysis of the modified carbon material at 300 °C in Ar. The Ni-N2 O2 /C catalyst showed excellent performance for the electrocatalytic reduction of O2 to H2 O2 through a two-electron transfer process in alkaline conditions, with a H2 O2 selectivity of 96 %. At a current density of 70â mA cm-2 , a H2 O2 production rate of 5.9â mol gcat. -1 h-1 was achieved using a three-phase flow cell, with good catalyst stability maintained over 8â h of testing. The Ni-N2 O2 /C catalyst could electrocatalytically reduce O2 in air to H2 O2 at a high current density, still affording a high H2 O2 selectivity (>90 %). A precise Ni-N2 O2 coordination was key to the performance.
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A challenging but pressing task to design and synthesize novel, efficient, and robust pH-universal hydrogen evolution reaction (HER) electrocatalysts for scalable and sustainable hydrogen production through electrochemical water splitting. Herein, we report a facile method to prepare an efficient and robust Ru-M (M=Ni, Mn, Cu) bimetal nanoparticle and carbon quantum dot hybrid (RuM/CQDs) for pH-universal HER. The RuNi/CQDs catalysts exhibit outstanding HER performance at all pH levels. The unexpected low overpotentials of 13, 58, and 18â mV shown by RuNi/CQDs allow a current density of 10â mA cm-2 in 1 m KOH, 0.5 m H2 SO4 , and 1 m PBS, respectively, for Ru loading at 5.93â µgRu cm-2 . This performance is among the best catalytic activities reported for any platinum-free electrocatalyst. Theoretical studies reveal that Ni doping results in a moderate weakening of the hydrogen bonding energy of nearby surface Ru atoms, which plays a critical role in improving the HER activity.
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Nanozymes have attracted extensive interest owing to their high stability, low cost and easy preparation, especially in the field of cancer therapy. However, the relatively low catalytic activity of nanozymes in the tumor microenvironment (TME) has limited their applications. Herein, we report a novel nanozyme (PtFe@Fe3 O4 ) with dual enzyme-like activities for highly efficient tumor catalytic therapy. PtFe@Fe3 O4 shows the intrinsic photothermal effect as well as photo-enhanced peroxidase-like and catalase-like activities in the acidic TME, thereby effectively killing tumor cells and overcoming the tumor hypoxia. Importantly, a possible photo-enhanced synergistic catalytic mechanism of PtFe@Fe3 O4 was first disclosed. We believe that this work will advance the development of nanozymes in tumor catalytic therapy.
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Catalasa/metabolismo , Nanopartículas del Metal/uso terapéutico , Neoplasias Pancreáticas/terapia , Peroxidasa/metabolismo , Animales , Apoptosis , Catálisis , Proliferación Celular , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Neoplasias Pancreáticas/enzimología , Neoplasias Pancreáticas/patología , Células Tumorales Cultivadas , Hipoxia Tumoral , Microambiente Tumoral , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Fructokinase (FRK) proteins play important roles in catalyzing fructose phosphorylation and participate in the carbohydrate metabolism of storage organs in plants. To investigate the roles of FRKs in cassava tuber root development, seven FRK genes (MeFRK1-7) were identified, and MeFRK1-6 were isolated. Phylogenetic analysis revealed that the MeFRK family genes can be divided into α (MeFRK1, 2, 6, 7) and ß (MeFRK3, 4, 5) groups. All the MeFRK proteins have typical conserved regions and substrate binding residues similar to those of the FRKs. The overall predicted three-dimensional structures of MeFRK1-6 were similar, folding into a catalytic domain and a ß-sheet ''lid" region, forming a substrate binding cleft, which contains many residues involved in the binding to fructose. The gene and the predicted three-dimensional structures of MeFRK3 and MeFRK4 were the most similar. MeFRK1-6 displayed different expression patterns across different tissues, including leaves, stems, tuber roots, flowers, and fruits. In tuber roots, the expressions of MeFRK3 and MeFRK4 were much higher compared to those of the other genes. Notably, the expression of MeFRK3 and MeFRK4 as well as the enzymatic activity of FRK were higher at the initial and early expanding tuber stages and were lower at the later expanding and mature tuber stages. The FRK activity of MeFRK3 and MeFRK4 was identified by the functional complementation of triple mutant yeast cells that were unable to phosphorylate either glucose or fructose. The gene expression and enzymatic activity of MeFRK3 and MeFRK4 suggest that they might be the main enzymes in fructose phosphorylation for regulating the formation of tuber roots and starch accumulation at the tuber root initial and expanding stages.
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Fructoquinasas/genética , Genes de Plantas , Manihot/enzimología , Manihot/genética , Familia de Multigenes , Secuencias de Aminoácidos , Secuencia de Aminoácidos , Cromosomas de las Plantas/genética , Clonación Molecular , Secuencia Conservada , ADN Complementario/genética , Exones/genética , Fructoquinasas/química , Fructoquinasas/metabolismo , Perfilación de la Expresión Génica , Regulación Enzimológica de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Prueba de Complementación Genética , Intrones/genética , Filogenia , Raíces de Plantas/genética , Tubérculos de la Planta/genética , Dominios Proteicos , Saccharomyces cerevisiae/metabolismo , Alineación de Secuencia , Análisis de Secuencia de ADN , Especificidad por SustratoRESUMEN
Faceted NiO nanoparticles preferentially exposing high surface energy planes demand attention due to their excellent electrocatalytic properties. However, the activity of faceted NiO nanoparticles generally remains suboptimal due to their large lateral size and thickness, which severely limits the availability of coordinatively unsaturated active reactive edge and corner sites. Here, ultrafine NiO nanosheets with a platelet size of â¼4.0 nm and thickness (â¼1.1 nm) stabilized by TiO2 were successfully prepared by calcination of a monolayer layered double hydroxide precursor. The ultrafine NiO nanosheets displayed outstanding performance in electrochemical water oxidation due to a high proportion of reactive NiO {110} facets, intrinsic Ni(3+) and Ti(3+) sites, and abundant interfaces, which act synergistically to promote H2O adsorption and facilitate charge-transfer.
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We report an effective and universal approach for the preparation of ultrathin single- or multiple-component transition-metal hydroxide (TMH) nanosheets with thickness below 5â nm. The unique synthesis benefits from the gradual decomposition of the preformed metal-boron (M-B, M=Fe, Co, Ni, NiCo) composite nanospheres which facilitates the formation of ultrathin nanosheets by the oxidation of the metal and the simultaneous release of boron species. The high specific surface area of the sheets associated with their ultrathin nature promises a wide range of applications. For example, we demonstrate the remarkable adsorption ability of Pb(II) and As(V) in waste water by the ultrathin FeOOH nanosheets. More interestingly, the process can be extended simply to the synthesis of composite structures of metal alloy hollow shells encapsulated by TMH nanosheets, which show excellent catalytic activity in the Heck reaction.
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Photoinduced syntheses offer significant advantages over conventional thermal strategies, including improved control over reaction kinetics and low synthesis temperatures, affording nanoparticles with nontrivial and thermodynamically unstable structures. However, the photoinduced syntheses of non-metallic nanocrystalline products (such as metal sulfides) have not yet been reported. Herein, we demonstrate the first photoinduced synthesis of ultrafine (sub-2â nm) Ag2 S quantum dots (QDs) from Ag nanoparticles at 10 °C. By thorough investigation of the mechanism for the transformation, a fundamental link was established between the intrinsic structures of the molecular intermediates and the final Ag2 S products. Our results confirm the viability of low-temperature photochemical approaches in metal sulfide synthesis, and demonstrate a new rule which could be followed in it.
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Lycorine, which is the most abundant alkaloid isolated from the Amaryllidaceae family of plants, reportedly exhibits promising anticancer activities. Herein, a series of novel lycorine derivatives were synthesized and evaluated for their in vitro inhibitory activities against seven different cancer cell lines, including A549, HCT116, SK-OV-3, NCI-H460, K562, MCF-7 and HL-60. The results indicated that compounds bearing diverse amine substituents at the C-2 position demonstrated good anticancer activities. The selectivity towards different cancer cell lines of the synthesized derivatives is discussed.
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Alcaloides de Amaryllidaceae/administración & dosificación , Alcaloides de Amaryllidaceae/síntesis química , Antineoplásicos/administración & dosificación , Antineoplásicos/síntesis química , Fenantridinas/administración & dosificación , Fenantridinas/síntesis química , Alcaloides de Amaryllidaceae/química , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Células HCT116 , Humanos , Liliaceae/química , Fenantridinas/química , Extractos Vegetales/química , Relación Estructura-ActividadRESUMEN
Graphene nanosheet-supported ultrafine metal nanoparticles encapsulated by thin mesoporous SiO2 layers were prepared and used as robust catalysts with high catalytic activity and excellent high-temperature stability. The catalysts can be recycled and reused in many gas- and solution-phase reactions, and their high catalytic activity can be fully recovered by high-temperature regeneration, should they be deactivated by feedstock poisoning. In addition to the large surface area provided by the graphene support, the enhanced catalytic performance is also attributed to the mesoporous SiO2 layers, which not only stabilize the ultrafine metal nanoparticles, but also prevent the aggregation of the graphene nanosheets. The synthetic strategy can be extended to other metals, such as Pd and Ru, for preparing robust catalysts for various reactions.
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Pain is a clinical condition that is currently of great concern and is often caused by tissue or nerve damage or occurs as a concomitant symptom of a variety of diseases such as cancer. Severe pain seriously affects the functional status of the body. However, existing pain management programs are not fully satisfactory. Therefore, there is a need to delve deeper into the pathological mechanisms underlying pain generation and to find new targets for drug therapy. Sphingolipids (SLs), as a major component of the bilayer structure of eukaryotic cell membranes, also have powerful signal transduction functions. Sphingolipids are abundant, and their intracellular metabolism constitutes a huge network. Sphingolipids and their various metabolites play significant roles in cell proliferation, differentiation, apoptosis, etc., and have powerful biological activities. The molecules related to sphingolipid metabolism, mainly the core molecule ceramide and the downstream metabolism molecule sphingosine-1-phosphate (S1P), are involved in the specific mechanisms of neurological disorders as well as the onset and progression of various types of pain, and are closely related to a variety of pain-related diseases. Therefore, sphingolipid metabolism can be the focus of research on pain regulation and provide new drug targets and ideas for pain.