In Situ Photodeposition of Gold Nanoparticles with Exposed High-Activity Crystal Facets under Different Sacrificial Agents.

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.

Activation of GPR81 by lactate drives tumour-induced cachexia.

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.

A Sensitive Probe of Meso-Cyanophenyl Substituted BODIPY Derivative as Fluorescent Chemosensor for the Detection of Multiple Heavy Metal Ions.

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.

Investigating the Properties of Triangle Terthiophene and Triphenylamine Configured Propeller-like Photochromic Dye with Ethyne Bridge.

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 (˃ 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.

CD206+ M2-like macrophages protect against intervertebral disc degeneration partially by targeting R-spondin-2.

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.

Identification of Key Prognostic Alternative Splicing Events of Costimulatory Molecule-Related Genes in Colon Cancer.

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.

Diazo-carboxyl Click Derivatization Enables Sensitive Analysis of Carboxylic Acid Metabolites in Biosamples.

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.

Recent Progress on Hydrogen Production from Ammonia Decomposition: Technical Roadmap and Catalytic Mechanism.

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.

Influence of macrophage polarization in herniated nucleus pulposus tissue on clinical efficacy after lumbar discectomy.

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.

Two 3D Ln(III)-MOFs Based on Phosphineoxide Ligand: Synthesis, Structure Luminescent and Photocatalytic Properties.

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%.

Photo-Induced Fluorochromism of a Star-Shaped Photochromic Dye with 2,4-Dimethylthiazole Attaching to Triangle Terthiophene.

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.

Investigating the Properties of Double Triangle Terthiophene Configured Dumbbell-Like Photochromic Dye with Ethyne and 1,3-Butadiene Bridge.

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 (˃ 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.

A Fluorescent Turn-On Sensor Toward Multiple Heavy Metal Ions Based on Meso-anisole Modified BODIPY Scaffold.

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.

Inducing supplier backup via manufacturer information sharing under supply disruption risk.

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.

Investigation of macrophage polarization in herniated nucleus pulposus of patients with lumbar intervertebral disc herniation.

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.

Investigation of Triangle Terthiophene and Hydroxyphenylbenzothiazole Configured Fluorescent Dye with a Triple Bond Bridge.

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.

Effect of lateral wedge-shaped orthopedic insole on patients with genu varus: A protocol for systematic review and meta-analysis.

BACKGROUND: Genu varus (GV) is a common deformity characterized by leg bending, which seriously threatens human health. At present, there is no definite conclusion to explain the cause of genu varus. The purpose of this study is to systematically review and meta-analysis the effectiveness and scientific basis of the clinical efficacy of customized orthopedic insoles on genu varus and hope to provide a reference for future research in this field. METHODS: The following electronic databases will be searched from inception to January 2022: Pubmed, Cochrane Library, MEDLINE, EMBASE, Web of Science, Weipu, Wanfang Data, and CNKI. Randomized controlled trials (RCTs) were collected to examine the effect of lateral wedge-shaped orthopedic insole on patients with genu varus. We will consider inclusion, select high-quality articles for data extraction and analysis, and summarize the intervention effect of lateral wedge orthotic insoles on patients with genu varus. Two reviewers will screen titles, abstracts, and full texts independently according to inclusion criteria; Data extraction and risk of bias assessment were performed in the included studies. We will use a hierarchy of recommended assessment, development, and assessment methods to assess the overall certainty of the evidence and report findings accordingly. Endnote X8 will be applied in selecting the study, Review Manager 5.3 will be applied in analyzing and synthesizing. RESULTS: The results will provide evidence for judging the effect of lateral wedge-shaped orthopedic insole on patients with genu varus. CONCLUSION: Our study will provide reliable evidence for the effect of lateral wedge-shaped orthopedic insole on patients with genu varus. TRAIL REGISTRATION: INPLASY registration number: INPLASY202190002 https://www.google.com/search?client=firefox-b-d&q=INPLASY202190002.

Effects of electrode materials and dimensions of an electrostatic spray scrubber on water droplet charging for dust removal.

Droplet charging is an effective method to enhance dust removal efficiency using an electrostatic spray scrubber (ESS). However, effects of the materials and dimensions of different electrodes on droplet charging efficiency have not been studied systematically. In this study, ring-shaped electrodes were selected to test effects of three types of electrode materials (copper, stainless steel, and graphite) with various dimensions on droplet charging efficiency. A Faraday pail charge measurement device was used to measure the droplet charge generated by the electrodes. A reduced factorial design with four factors was used in this study to investigate the charging efficiency affected by the factors. The four factors tested were electrode material, electrode diameter, nozzle height, and applied voltage. A 304L stainless steel electrode was found to achieve higher droplet charge-to-mass ratio (CMR) values than identically shaped electrodes made from either copper or graphite. The optimal stainless steel electrode inner diameter was 100 mm. The 304L stainless-steel electrode with this optimal diameter and a height of 45 mm achieved the highest mean CMR of 0.435 ± 0.002 mC kg-1 at an applied voltage of -11 kV with the bottom of the nozzle tip positioned 15 mm below the top of the electrode.Implications Currently, the low removal efficiency of submicron particles cannot meet the environmental control requirements of industrial applications that may have significant concentrations of particulate matter (PM) in this size range. As stricter environmental regulations are increasingly enforced, there is an urgent need to efficiently remove submicron dust particles from the air. Experiments show that the dust capture process is improved by charging droplets in the spray separator and reducing the secondary escape of dust particles in the electrostatic precipitatorAlthough high-voltage charging of droplets has been investigated in many studies, the effect of electrode material and size on droplet CMR is still not fully understood. The purpose of this study was to (1) quantify the performance of 304L stainless steel (304L SS), copper, and high-purity graphite electrodes for spray droplet CMR, (2) evaluate effects of the applied voltage, nozzle height, electrode material and dimension on CMR, and (3) optimize the specific values of key design factors and operating parameters that lead to the highest CMR. The results of this study aim to optimize electrostatic spray scrubbers to achieve high droplet CMR values.

Macrophage polarization regulates intervertebral disc degeneration by modulating cell proliferation, inflammation mediator secretion, and extracellular matrix metabolism.

Macrophage infiltration and polarization have been increasingly observed in intervertebral disc (IVD) degeneration (IDD). However, their biological roles in IDD are still unrevealed. We harvested conditioned media (CM) derived from a spectrum of macrophages induced from THP-1 cells, and examined how they affect nucleus pulposus cells (NPCs) in vitro, by studying cell proliferation, extracellular matrix (ECM) synthesis, and pro-inflammation expression; and in vivo by injection CM in a rat IDD model. Then, high-throughput sequencing was used to detect differentially expressed genes (DEGs). Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI) networks were used to further analysis. Higher CCR7+ (M1 marker) and CD206+ (M2 marker) cell counts were found in the degenerated human IVD tissues as compared with the control. Furthermore, the cell co-culture model showed M1CM attenuated NPC proliferation, downregulated the expression of ECM anabolic genes encoding aggrecan and collagen IIα1, upregulated the expression of ECM catabolic genes encoding MMP-13, and inflammation-related genes encoding IL-1ß, IL-6, and IL-12, while M2CM showed contrasting trends. In IDD model, higher histological scores and lower disc height index were found following M1CM treatment, while M2CM exhibited opposite results. M1CM injection decreased ECM anabolic and increased ECM catabolic, as well as the upregulation of inflammation-related genes after 8 weeks treatment, while M2CM slowed down these trends. Finally, a total of 637 upregulated and 655 downregulated genes were detected in M1CM treated NPCs, and 975 upregulated genes and 930 downregulated genes in the M2CM groups. The top 30 GO terms were shown and the most significant KEGG pathway was cell cycle in both groups. Based on the PPI analysis, the five most significant hub genes were PLK1, KIF20A, RRM2, CDC20, and UBE2C in the M1CM groups and RRM2, CCNB1, CDC20, PLK1, and UBE2C in the M2CM groups. In conclusion, macrophage polarization exhibited diverse roles in IDD progression, with M1CM exacerbating cell proliferation suppression and IVD degeneration, while M2CM attenuated IDD development. These findings may facilitate the further elucidation of the role of macrophage polarization in IDD, and provide novel insights into the therapeutic potential of macrophages.

M2 macrophage-conditioned medium inhibits intervertebral disc degeneration in a tumor necrosis factor-α-rich environment.

Inflammation is the primary pathological phenomenon associated with disc degeneration; the inflammatory cytokine tumor necrosis factor (TNF-α) plays a crucial role in this pathology. The anti-inflammatory and regenerative effects of M2 macrophages on nucleus pulposus cells (NPCs) in intervertebral disc degeneration (IDD) progression remain unknown. Here, M2 conditioned medium (M2CM) was harvested and purified from human acute monocytic leukaemia cell line (THP-1) cells and mouse peritoneal macrophages, respectively; it was used for culturing human NPCs and a mouse intervertebral disc (IVD) organ culture model. NPCs and IVD organ models were divided into three groups: group 1 treated with 10% fetal bovine serum (control); group 2 treated with 10 ng/ml TNF-α; and group 3 treated with 10 ng/ml TNF-α and M2CM (coculture group). After 2-14 days, cell proliferation, extracellular matrix synthesis, apoptosis, and NPC senescence were assessed. Cell proliferation was reduced in TNF-α-treated NPCs and inhibited in the M2CM co-culture treatment. Moreover, TNF-α treatment enhanced apoptosis, senescence, and expression of inflammatory factor-related genes, including interleukin-6, MMP-13, ADAMTS-4, and ADAMTS-5, whereas M2CM coculture significantly reversed these effects. In addition, co-culture with M2CM promoted aggrecan and collagen II synthesis, but reduced collagen Iα1 levels in TNF-α treatment groups. Using our established three-dimensional murine IVD organ culture model, we show that M2CM suppressed the inhibitory effect of TNF-α-rich environment. Therefore, co-culture with M2CM promotes cell proliferation and extracellular matrix synthesis and inhibits inflammation, apoptosis, and NPC senescence. This study highlights the therapeutic potential of M2CM for IDD.