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Direct current triboelectric nanogenerators (DC-TENGs) are a groundbreaking technology to capture micromechanical energy from the natural environment, which is crucial for directly powering sensor networks. However, the research bottleneck in enhancing the triboelectric electrification capability and charge storage capability of dielectrics has hindered the overall performance breakthroughs of the DC-TENG. Here, a field emission model-based DC-TENG (FEM-TENG) is proposed, inspired by lightning rods. The enhanced local electric field between dielectric materials and electrodes induces strong electron tunneling, which improves charge neutralization on the surface of materials and their internal charge storage space, thereby utilizing the dielectric volume effect effectively and strengthening triboelectricity. Guided by the field emission model, the FEM-TENG with a historic crest factor of 1.00375 achieves a groundbreaking record of an average power density of 16.061 W m-2 Hz-1 (1,591 W m-3 Hz-1), which is 5.36-fold of the latest DC-TENG. In particular, the FEM-TENG with high durability (100%) truly realizes the collection of breeze energy and continuously drives 50 thermohygrometers. Four additional applications exemplify the FEM-TENG, enabling comprehensive sensing of land, water, and air. This work proposes a paradigm strategy for the in-depth utilization of dielectric films, aiming to enhance the output power of DC-TENGs.
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Light-At-Night (LAN) is increasingly recognized and may has adverse health effects on children and adolescents, yet few studies have reported objective indoor LAN exposure levels for children and adolescents. In this study, we measured the indoor LAN exposure levels and duration among 897 children and adolescents aged 6-14 in Beijing, China, using portable photometers during both school days and weekends. Results indicate that the median indoor LAN exposure from 9:00 p.m. to 7:00 a.m. was 5.1 lx, with 31.8% of the subjects experiencing an average exposure above 10 lx. Additionally, from the perspective of cumulative high exposure duration, children and adolescents were exposed to more than 10 lx for approximately 64 min from 9:00 p.m. to 7:00 a.m. During the entire nighttime (from self-reported bedtime to wake-up time), the median exposure was 2.1 lx, with 16.6% averaging exposures above 10 lx. Exposure levels were significantly higher on weekends than on schooldays. Both girls and upper-grade students had higher levels of exposure and longer durations of high exposure. Girls in grade 7 (OR:2.56, 95%CI: 1.68-3.88) experienced the highest LAN exposure in our subjects compared to boys in grade 1-4. Our findings underscore the importance of promoting healthy light exposure behaviors among children and adolescents and reducing their light exposure environments to mitigate the potential health impacts of LAN.
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The energy conversion efficiency of conventional binary dielectric triboelectric nanogenerators is not satisfactory due to the limitations of material selection and triboelectrification, which motivates the design of more efficient multicomponent structures to reveal the charge accumulation mechanism for improving the energy conversion efficiency. Herein, a rotating quaternary dielectric triboelectric nanogenerator (Q-TENG) is designed to construct a self-powered system integrating illumination, sensing, and electrochemical decolorization. Through the equivalent capacitance model, the mechanisms for charge generation, transfer, and accumulation in a Q-TENG are elucidated to achieve efficient matching of quaternary dielectric materials and high output performance. At a wind speed of 3.5 m s-1, the peak power density of the Q-TENG reaches 44.94 W m-2, setting a new record for a wind-driven TENG. A 5 ppm solution of methyl orange is completely degraded by the wind-driven Q-TENG in <6 h. This work not only guides the direction for constructing more efficient TENG systems but also promotes the practical development of self-powered electrochemical systems.
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Objectives: The development of effective treatments for non-small cell lung cancer (NSCLC), particularly targeting the KRASG12C mutation, remains a challenge. In this study, we investigated the therapeutic potential of VT204, a small molecule inhibitor of KRASG12C, in NSCLC. Methods: To achieve the objectives, we conducted a comprehensive set of experimental methods. In vitro experiments involved the investigation of VT204 on proliferation, apoptosis, cell cycle dynamics, migration, invasion, and on the RAF/MEK/ERK signaling pathway in NCI-H358 cells. In addition, in vivo experiments were performed to evaluate the inï¬uence of VT204 on tumor growth. Results: We demonstrated that VT204 effectively suppressed cell proliferation in NCI-H358 cells, with significant inhibition observed at a concentration of 8â µM. Colony formation assays further supported the inhibitory effect of VT204 on NCI-H358 cell growth. Moreover, VT204 exhibited notable effects on suppressing migration and invasion capacities of NCI-H358 cells, indicating its potential as a metastasis-inhibiting agent. Mechanistic investigations revealed that VT204 induced apoptosis and G2M-phase cell cycle arrest in NCI-H358 cells. Additionally, VT204 modulated the RAF/MEK/ERK signaling pathway, leading to reduced phosphorylation of ERK. In vivo studies using xenograft models confirmed the inhibitory effect of VT204 on NCI-H358 tumor growth. Conclusion: These findings highlight VT204 as a promising therapeutic candidate for NSCLC targeting the KRASG12C mutation.
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Apoptose , Carcinoma Pulmonar de Células não Pequenas , Movimento Celular , Proliferação de Células , Neoplasias Pulmonares , Mutação , Proteínas Proto-Oncogênicas p21(ras) , Ensaios Antitumorais Modelo de Xenoenxerto , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Animais , Camundongos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Proliferação de Células/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Proteínas Proto-Oncogênicas p21(ras)/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Modelos Animais de DoençasRESUMO
In situ photodeposition presents a powerful approach for integrating noble metal co-catalysts onto semiconductor surfaces. However, achieving precise control over the microstructure of the deposited co-catalyst remains a major challenge. Au nanoparticles (NPs) are deposited onto H-KCNO using HAuCl4 in the presence of various sacrificial agents in this study. Notably, the choice of sacrificial agent decisively influences the exposed crystal facets, loaded content, and particle size of the deposited Au NPs. Importantly, in situ photodeposition under an ethanol solution facilitates the exposure of the highly active (111) and (220) crystal facets of Au. The introduction of Au NPs significantly enhances photocatalytic hydrogen evolution, achieving rates of 4.93, 57.88, and 15.44 µmol/h for H-KCNO/Au-(water, ethanol, and lactic acid), respectively. The observed photocatalytic activity for hydrogen evolution indicates that the exposure of the highly active planes emerges as critical for significant performance enhancement. Photoelectrochemical and photoluminescence measurements suggest that the highly active (111) and (220) crystal facets effectively segregate sites for redox reactions, thereby impeding the recombination of photogenerated electron-hole pairs.
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Cachexia affects 50-80% of patients with cancer and accounts for 20% of cancer-related death, but the underlying mechanism driving cachexia remains elusive. Here we show that circulating lactate levels positively correlate with the degree of body weight loss in male and female patients suffering from cancer cachexia, as well as in clinically relevant mouse models. Lactate infusion per se is sufficient to trigger a cachectic phenotype in tumour-free mice in a dose-dependent manner. Furthermore, we demonstrate that adipose-specific G-protein-coupled receptor (GPR)81 ablation, similarly to global GPR81 deficiency, ameliorates lactate-induced or tumour-induced adipose and muscle wasting in male mice, revealing adipose GPR81 as the major mediator of the catabolic effects of lactate. Mechanistically, lactate/GPR81-induced cachexia occurs independently of the well-established protein kinase A catabolic pathway, but it is mediated by a signalling cascade sequentially activating Gi-Gßγ-RhoA/ROCK1-p38. These findings highlight the therapeutic potential of targeting GPR81 for the treatment of this life-threatening complication of cancer.
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Caquexia , Ácido Láctico , Neoplasias , Receptores Acoplados a Proteínas G , Caquexia/metabolismo , Caquexia/etiologia , Animais , Receptores Acoplados a Proteínas G/metabolismo , Camundongos , Humanos , Ácido Láctico/metabolismo , Masculino , Feminino , Neoplasias/metabolismo , Neoplasias/complicações , Transdução de SinaisRESUMO
Synthesis-oriented design led us to the construction of a propeller-like dye, containing the triangle terthiophene and triphenylamine units. It reveals typical photochromic properties with alternated UV (390 nm) and visible light (Ë 440 nm) irradiation and the dye solution (in THF) color was also toggled between yellow-green and colorless. A new absorption band was observed in visible region (415-600 nm). Additionally, the photochromic dye was highly emissive with the absolute quantum yield being 0.27. After UV light irradiation, the emission was quenched significantly (Φ = 0.08) at photo-stationary state, and thus establishing a switchable emission "on-off" system by alternated UV/visible light irradiation cycle. Detailed structural analysis was carried out based on the optimized dye structure. Both the antiparallel conformation and the distance of reactive carbon atoms (< 4.2 Å) led to the smoothly photochromic behavior.
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A fluorescent turn-on chemosensor (BA) was constructed by attaching bis(pyridin-2-ylmethyl)-amine (DPA) unit to the BODIPY scaffold. It can give a prominent green/yellow fluorescent response selectivity with each of Zn2+/Hg2+/Cd2+/Ca2+/Mn2+/Pb2+/Al3+. The 1:1 stoichiometry of BA and metal ions was drawn from the analysis of Job's plot. The limit detection of BA in recognition of Zn2+/Hg2+/Cd2+/Ca2+/Mn2+/Pb2+/Al3+ is ranged in 50.8-146.6 nM. There exists a linear relationship between the fluorescence intensity and concentration of metal ions (Zn2+: 4-15 µM). The mechanism of fluorescence signal "turn-on" is based on the photo induced transfer (PET) in the excited state of BA. The coordinated metal ions significantly weakened the electron-donating ability nitrogen atom in DPA, thus recovering the emission character of BODIPY. The substituted group at the phenyl ring in meso-position of BODIPY scaffold determines the recognizable list of metal ions.
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OBJECTIVE: This study aimed to explore the specific function of M2 macrophages in intervertebral disc degeneration (IDD). METHODS: Intervertebral disc (IVD) samples from normal (n = 4) and IDD (n = 6) patients were collected, and the expression of M2-polarized macrophage marker, CD206, was investigated using immunohistochemical staining. Nucleus pulposus cells (NPCs) in a TNF-α environment were obtained, and a mouse caudal IVD puncture model was established. Mice with Rheb deletions, specifically in the myeloid lineage, were generated and subjected to surgery-induced IDD. IDD-induced damage and cell apoptosis were measured using histological scoring, X-ray imaging, immunohistochemical staining, and TdT-mediated dUTP nick end labeling (TUNEL) assay. Finally, mice and NPCs were treated with R-spondin-2 (Rspo2) or anti-Rspo2 to investigate the role of Rspo2 in IDD. RESULTS: Accumulation of CD206 in human and mouse IDD tissues was detected. Rheb deletion in the myeloid lineage (RheBcKO) increased the number of CD206+ M2-like macrophages (mean difference 18.6% [15.7-21.6%], P < 0.001), decreased cell apoptosis (mean difference -15.6% [-8.9 to 22.2%], P = 0.001) and attenuated the IDD process in the mouse IDD model. NPCs treated with Rspo2 displayed increased extracellular matrix catabolism and apoptosis; co-culture with a conditioned medium derived from RheBcKO mice inhibited these changes. Anti-Rspo2 treatment in the mouse caudal IVD puncture model exerted protective effects against IDD. CONCLUSIONS: Promoting CD206+ M2-like macrophages could reduce Rspo2 secretion, thereby alleviating experimental IDD. Rheb deletion may help M2-polarized macrophages accumulate and attenuate experimental IDD partially by inhibiting Rspo2 production. Hence, M2-polarized macrophages and Rspo2 may serve as therapeutic targets for IDD.
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Degeneração do Disco Intervertebral , Disco Intervertebral , Núcleo Pulposo , Humanos , Camundongos , Animais , Degeneração do Disco Intervertebral/patologia , Disco Intervertebral/metabolismo , Núcleo Pulposo/metabolismo , Apoptose , Modelos Animais de Doenças , Macrófagos/metabolismoRESUMO
OBJECTIVE: This study aimed to explore the key alternative splicing events in costimulatory molecule-related genes in colon cancer and to determine their correlation with prognosis. METHODS: Gene expression RNA-sequencing data, clinical data, and SpliceSeq data of colon cancer were obtained from The Cancer Genome Atlas. Differentially expressed alternative splicing events in genes were identified, Followed by correlation analysis of genes corresponding to differentially expressed alternative splicing events with costimulatory molecule-related genes. Survival analysis was conducted using differentially expressed alternative splicing events in these genes and a prognostic model was constructed. Functional enrichment, proteinprotein interaction network, and splicing factor analyses were performed. RESULTS: In total, 6504 differentially expressed alternative splicing events in 3949 genes were identified between tumor and normal tissues. Correlation analysis revealed 3499 differentially expressed alternative splicing events in 2168 costimulatory molecule-related genes. Moreover, 328 differentially expressed alternative splicing events in 288 costimulatory molecule-related genes were associated with overall survival. The prognostic models constructed using these showed considerable power in predicting survival. The ubiquitin A-52 residue ribosomal protein fusion product 1 and ribosomal protein S9 were the hub nodes in the protein-protein interaction network. Furthermore, one splicing factor, splicing factor proline and glutamine-rich, was significantly associated with patient prognosis. Four splicing factor-alternative splicing pairs were obtained from four alternative splicing events in three genes: TBC1 domain family member 8 B, complement factor H, and mitochondrial fission 1. CONCLUSION: The identified differentially expressed alternative splicing events of costimulatory molecule-related genes may be used to predict patient prognosis and immunotherapy responses in colon cancer.
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Carboxylic acids are central metabolites in bioenergetics, signal transduction, and post-translation protein regulation. However, the quantitative analysis of carboxylic acids as an indispensable part of metabolomics is prohibitively challenging, particularly in trace amounts of biosamples. Here we report a diazo-carboxyl/hydroxylamine-ketone double click derivatization method for the sensitive analysis of hydrophilic, low-molecular-weight carboxylic acids. In general, our method renders a 5- to 2000-fold higher response in mass spectrometry along with improved chromatographic separation. With this method, we presented the near-single-cell analysis of carboxylic acid metabolites in 10 mouse egg cells before and after fertilization. Malate, fumarate, and ß-hydroxybutyrate were found to decrease after fertilization. We also monitored the isotope labeling kinetics of carboxylic acids inside adherent cells cultured in 96-well plates during drug treatment. Finally, we applied this method to plasma or serum samples (5 µL) collected from mice and humans under pathological and physiological conditions. The double click derivatization method paves a way toward single-cell metabolomics and bedside diagnostics.
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Ácidos Carboxílicos , Espectrometria de Massas em Tandem , Humanos , Animais , Camundongos , Ácidos Carboxílicos/química , Espectrometria de Massas em Tandem/métodos , Metabolômica/métodos , Marcação por Isótopo/métodosRESUMO
Ammonia decomposition has attracted significant attention in recent years due to its ability to produce hydrogen without emitting carbon dioxide and the ease of ammonia storage. This paper reviews the recent developments in ammonia decomposition technologies for hydrogen production, focusing on the latest advances in catalytic materials and catalyst design, as well as the research progress in the catalytic reaction mechanism. Additionally, the paper discusses the advantages and disadvantages of each method and the importance of finding non-precious metals to reduce costs and improve efficiency. Overall, this paper provides a valuable reference for further research on ammonia decomposition for hydrogen production.
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Amônia , Metais , Catálise , HidrogênioRESUMO
Background: Low back pain or sciatic pain because of lumbar intervertebral disc herniation (LDH) is caused by mechanical compression and/or an inflammatory component on the nerve root. However, it is difficult to define to what extent each component contributes to the pain. This study attempted to explore the effects of macrophage polarization on clinical symptoms in patients experiencing LDH after surgery, and investigated the association between macrophage cell percentages and clinical efficacy. Methods: This study retrospectively harvested nucleus pulposus (NP) tissue samples from 117 patients. Clinical symptoms and efficacy using the visual analog scale (VAS) and Oswestry Disability Index (ODI) were evaluated at different time points preoperatively and postoperatively. CD68, CCR7, CD163, and CD206 were selected as macrophage phenotypic markers. Results: Seventy-six samples showed positive expression of macrophage markers in NP samples of patients with LDH, whereas 41 patients displayed negative results. No significant differences were detected between the two groups, involvement of several demographic data, and preoperative clinical findings. With respect to the macrophage-positive group, no significant correlation was detected between the positive rate of the four markers and the VAS score or ODI after surgery. However, patients with NP samples positive for CD68 and CCR7 expression showed significantly lower VAS scores 1 week after surgery compared with those in the negative group. Moreover, the improvement in VAS score showed a strong positive correlation with CD68- and CCR7-positive cell percentages. Conclusions: Our results indicated that pro-inflammatory M1 macrophages may be associated with the reduction of chronic pain after surgery. Therefore, these findings contribute to better personalized pharmacological interventions for patients with LDH, considering the heterogeneity of pain.
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Two new 3D metal-organic frameworks (MOFs) ZZUT1 and ZZUT2 were prepared through the reaction of tris-(4-carboxylphenyl) phosphineoxide (H3TPO) ligand with nitrate of neodymium and praseodymium by solvothermal method. The structure, fluorescence and photocatalytic properties of ZZUT1 and ZZUT2 were studied. The crystalline structure of two 3D Ln(III)-MOFs both exhibit triclinic system and P-1 space group. The results of fluorescence analysis showed that two 3D Ln(III)-MOFs could selectively recognize acetone molecule through the fluorescence quenching mechanism. Meanwhile, ZZUT1 and ZZUT2 showed good adsorption and degradation ability on organic dye methylene blue (MB) in photocatalytic condition, and the degradation efficiency can reach to more than 90%.
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A photochrmic triangle terthiophene dye with 2,4-dimethylthiazole attached was synthesized and shows regular photochromic properties when irradiated with UV/Vis light alternately. It was found that the attaching of 2,4-dimethylthiazole has a significant effect on both the photochromism and fluorescence of triangle terthiophene. During the photocyclizatioin prcess, not only the color but also the fluorescence of the dye in THF can be toggled between ring-open and ring-closed forms of the dye. Additionally, the absolute quantum yields (AQY) of ring-open and ring-closed forms of the dye (0.32/0.58) were greatly larger than the literature report. Along with the 254 nm light irradiation, the fluorescence color changed from deep blue (428 nm) to sky blue (486 nm) in THF. A fluorochromism cycle could be established based on the UV/visible light irradiation cycle, which provides a strategy for the design of new type fluorescent diarylethene derivatives for biological application.
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Dumbbell-like photochromic dyes were constructed by incorporation of double triangle terthiophene with ethyne or 1,3-butadiene bridge. Regular photochromic behavior was investigated with alternated UV (365 nm) and Visible light (Ë 400 nm) irradiation. However, the different bridge group leads to distinct difference in their photochromic wavelength. For the ethyne bridged triangle terthiophene (DT1), the photochromic wavelength was observed around 500-700 nm (peak value: 605 nm) and the solution turned to red with 365 nm light irradiation. However, the photochromic wavelength was blue shift to 418-550 nm and the solution was turned to light yellow for 1,3-butadiene bridged dye (DT2). Both of the colored solution can be bleached via visible light irradiation. Additionally, the two dyes in THF were emissive with absolute quantum yield (QY) of 0.36/0.40. Along with the photo-induced photocyclization process, the emissive solution can be effectively quenched at photo-stationary sate (Φ = 0.05/0.04). And emission "on-off" cycle could be established based on the UV/visible light irradiation cycle.
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What comes along with the repeating and wide-range COVID-19 outbreak is the increasingly latent supply disruption risk encountered by global supply chains. Among many instruments to enhance supply chain resilience, backup production may be an appropriate choice, whereas how to induce the supplier backup becomes an obstacle. In this study, we investigate a supply chain in the context of the crisis-like new normal with supply disruption risk, wherein a manufacturer uses private demand information as a strategic lever, according to which a supplier decides whether to adopt backup production. Our findings reveal that the supplier's equilibrium decision on the adoption of backup production exhibits a cutoff structure when the manufacturer shares demand information. Moreover, we uncover the effect of information sharing on backup decision. In specific, information sharing impedes the adoption of backup production under low demand potential while promoting it under high demand potential. Interestingly, the manufacturer may have the incentive to share the demand information with the upstream supplier if the demand variability is low and the backup cost is moderate, and such information sharing stimulates the supplier to adopt the backup production. Counterintuitively, the manufacturer and the whole supply chain may display nonmonotonic relations to the backup cost as a result.
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A fluorescent turn-on sensor (BOPA) was configured by anchoring bis(pyridin-2-ylmethyl)-amine (DPA) unit to the BODIPY scaffold. It exhibits highly sensitivity and selectivity towards Pb2+, Ba2+, Cr3+, Cd2+, Hg2+, Zn2+ against the competent metal ions. Job's plot analysis supports the 1:1 stoichiometry of BOPA and metal ions. And linear relationship between fluorescence intensity and concentration of Zn2+ (representative metal ion) was observed over the range 0 ~ 20 µM Zn2+. The limit detection of BOPA in recognition of Pb2+, Ba2+, Cr3+, Cd2+, Hg2+, Zn2+ was ranged from 15.99 to 43.57 nM. Photo induced transfer (PET) in the excited state of BOPA determines the emission "off/on". Coordination of metal ions by DPA significantly weakened the electron-donating ability of nitrogen atom and inhibits the PET, recovering emission of BODIPY. In addition, the attachment of anisole at meso-position of BODIPY finely modulated the recognition of metal ions category.
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A photochromic dye was constructed by incorporation of a carbon-carbon triple bond spaced triangle terthiophene skeleton and hydroxyphenylbenzothiazole. Regular photochromic behavior was investigated with alternated UV (254 nm) and visible light (≥ 400 nm) irradiation. The color of dye in solution can be cycled between pink and colorless. Additionally, the dye solution strongly fluoresces in THF with the absolute quantum yield (QY) being 0.56. When irradiation with 254 nm light, the emissive solution can be effectively quenched to photo-stationary sate (Φ = 0.05). An emission "on-off" cycle could be established based on the UV/visible light irradiation cycle. The photochromic dye also exhibits good photo- and thermal-stability at room temperature. The emission decay profile indicates typical single component character with the fluorescence lifetime being 6.68 ns. The emission color was determined by the CIE 1931 coordinates of x = 0.14, y = 0.25 in the blue region.
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Macrophage infiltration and polarization during lumbar intervertebral disc herniation (LDH) have attracted increased attention but their role remains unclear. To explore macrophage polarization in herniated nucleus pulposus (NP) tissue of patients with LDH and investigate the association between cell frequency and different clinical characteristics or symptoms, we conducted a retrospective study by analyzing NP tissue samples from 79 patients. Clinical features and symptoms, using the visual analog scale (VAS) and Oswestry disability index (ODI), were collected. The macrophage markers CD68, CCR7, CD163, and CD206; pro-inflammatory cytokine TNF-α; and anti-inflammatory factor IL-4 were analyzed by immunohistochemistry. The frequency of polarized macrophages and positivity rate of pro- and anti-inflammatory cytokines showed significant differences in some of clinical characteristics. Specifically, higher CCR7+ and TNF-α + proportions were identified in the high-intensity zone (HIZ) and the type of extrusion and sequestration NP tissue than in non-HIZ and protrude NP tissue. Higher CD206+ and IL-4+ proportion were detected in Modic changes. However, no differences in gender, age, smoking status, Pfirrmann grade, analgesic use, leg pain duration, and segments were found between groups. CD68+ , CCR7+ , and CD206+ cell proportions, and TNF-α and IL-4 showed positive associations with VAS scores preoperation. Associations between ODI and the macrophages markers were weak/insignificant. Our results indicated that macrophage polarization or macrophage-like cells contribute to LDH pathological features. Macrophage populations displaying significant associations with VAS score reflected continuous M1/M2 transition contributing to pain during LDH. These findings may contribute to enhanced/personalized pharmacological interventions for patients with LDH considering pain heterogeneity.