Colorectal cancer subtyping and immune landscape analysis based on natural killer cell-related genes.

BACKGROUND AND STUDY AIMS: The prognosis of colorectal cancer (CRC) is related to natural killer (NK) cells, but the molecular subtype features of CRC based on NK cells are still unknown. This study aimed to identify NK cell-related molecular subtypes of CRC and analyze the survival status and immune landscape of patients with different subtypes. PATIENTS/MATERIAL AND METHODS: mRNA expression data, single nucleotide variant (SNV) data, and clinical information of CRC patients were obtained from The Cancer Genome Atlas. Differentially expressed genes (DEGs) were obtained through differential analysis, and the intersection was taken with NK cell-associated genes to obtain 103 NK cell-associated CRC DEGs (NCDEGs). Based on NCDEGs, CRC samples were divided into three clusters through unsupervised clustering analysis. Survival analysis, immune analysis, Gene Set Enrichment Analysis (GSEA), and tumor mutation burden (TMB) analysis were performed. Finally, NCDEG-related small-molecule drugs were screened using the CMap database. RESULTS: Survival analysis revealed that cluster2 had a lower survival rate than cluster1 and cluster3 (p < 0.05). Immune infiltration analysis found that the immune infiltration levels and immune checkpoint expression levels of cluster1_3 were substantially higher than those of cluster2, and the tumor purity was the opposite (p < 0.05). GSEA presented that cluster1_3 was significantly enriched in the chemokine signaling pathway, ECM receptor interaction, and antigen processing and presentation pathways (p < 0.05). The TMB of cluster1_3 was significantly higher than that of cluster2 (p < 0.05). Genes with the highest mutation rate in CRC were APC, TP53, TTN, and KRAS. Drug prediction results showed that small-molecule drugs that reverse the upregulation of NCDEGs, deoxycholic acid, dipivefrine, phenformin, and other drugs may improve the prognosis of CRC. CONCLUSION: NK cell-associated CRC subtypes can be used to evaluate the tumor characteristics of CRC patients and provide an important reference for CRC patients.

Mechanosensitive protein polycystin-1 promotes periosteal stem/progenitor cells osteochondral differentiation in fracture healing.

Background: Mechanical forces are indispensable for bone healing, disruption of which is recognized as a contributing cause to nonunion or delayed union. However, the underlying mechanism of mechanical regulation of fracture healing is elusive. Methods: We used the lineage-tracing mouse model, conditional knockout depletion mouse model, hindlimb unloading model and single-cell RNA sequencing to analyze the crucial roles of mechanosensitive protein polycystin-1 (PC1, Pkd1) promotes periosteal stem/progenitor cells (PSPCs) osteochondral differentiation in fracture healing. Results: Our results showed that cathepsin (Ctsk)-positive PSPCs are fracture-responsive and mechanosensitive and can differentiate into osteoblasts and chondrocytes during fracture repair. We found that polycystin-1 declines markedly in PSPCs with mechanical unloading while increasing in response to mechanical stimulus. Mice with conditional depletion of Pkd1 in Ctsk+ PSPCs show impaired osteochondrogenesis, reduced cortical bone formation, delayed fracture healing, and diminished responsiveness to mechanical unloading. Mechanistically, PC1 facilitates nuclear translocation of transcriptional coactivator TAZ via PC1 C-terminal tail cleavage, enhancing osteochondral differentiation potential of PSPCs. Pharmacological intervention of the PC1-TAZ axis and promotion of TAZ nuclear translocation using Zinc01442821 enhances fracture healing and alleviates delayed union or nonunion induced by mechanical unloading. Conclusion: Our study reveals that Ctsk+ PSPCs within the callus can sense mechanical forces through the PC1-TAZ axis, targeting which represents great therapeutic potential for delayed fracture union or nonunion.

Exosomes derived from mesenchymal stem cells in diabetes and diabetic complications.

Diabetes, a group of metabolic disorders, constitutes an important global health problem. Diabetes and its complications place a heavy financial strain on both patients and the global healthcare establishment. The lack of effective treatments contributes to this pessimistic situation and negative outlook. Exosomes released from mesenchymal stromal cells (MSCs) have emerged as the most likely new breakthrough and advancement in treating of diabetes and diabetes-associated complication due to its capacity of intercellular communication, modulating the local microenvironment, and regulating cellular processes. In the present review, we briefly outlined the properties of MSCs-derived exosomes, provided a thorough summary of their biological functions and potential uses in diabetes and its related complications.

Unconscious Integration of Categorical Relationship of Two Subliminal Numbers in Comparison with "5".

Many studies have shown that the brain can process subliminal numerals, i.e., participants can categorize a subliminal number into two categories: greater than 5 or less than 5. In the context of many studies on the unconscious integration of multiple subliminal stimuli, the issue of whether multiple subliminal numbers can be integrated is contentious. The same-different task is regarded as a perfect tool to explore unconscious integration. In the two experiments reported, we used a same-different task in which a pair of masked prime numbers was followed by a pair of target numbers, and participants were asked to decide whether the two target numbers were on the same (both smaller or larger than 5) or different sides (one smaller, the other larger than 5) of 5 in magnitude. The results indicated that the prime numbers could be categorized unconsciously, which was reflected by the category priming effect, and that the unconscious category relationship of the two prime numbers could affect the judgment on the category relationship of the two target numbers, as reflected by the response priming effect. The duration of the prime-to-target interstimulus interval (ISI) was also manipulated, showing a positive compatibility effect (PCE) of category priming and a negative compatibility effect (NCE) of response priming no matter whether the ISI was short (50 ms) or long (150 ms). The NCE, which occurred when the prime-to-target ISI was relatively short in this study, contradicted the conventional view but was consistent with previous results of unconscious integration based on an attention modulation mechanism. Importantly, this study provided evidence for the still-under-debate issue of numerical information integration.

131I Induced In Vivo Proteolysis by Photoswitchable azoPROTAC Reinforces Internal Radiotherapy.

Photopharmacology, incorporating photoswitches such as azobenezes into drugs, is an emerging therapeutic method to realize spatiotemporal control of pharmacological activity by light. However, most photoswitchable molecules are triggered by UV light with limited tissue penetration, which greatly restricts the in vivo application. Here, this study proves that 131I can trigger the trans-cis photoisomerization of a reported azobenezen incorporating PROTACs (azoPROTAC). With the presence of 50 µCi mL-1 131I, the azoPROTAC can effectively down-regulate BRD4 and c-Myc levels in 4T1 cells at a similar level as it does under light irradiation (405 nm, 60 mW cm-2). What's more, the degradation of BRD4 can further benefit the 131I-based radiotherapy. The in vivo experiment proves that intratumoral co-adminstration of 131I (300 µCi) and azoPROTC (25 mg kg-1) via hydrogel not only successfully induce protein degradation in 4T1 tumor bearing-mice but also efficiently inhibit tumor growth with enhanced radiotherapeutic effect and anti-tumor immunological effect. This is the first time that a radioisotope is successfully used as a trigger in photopharmacology in a mouse model. It believes that this study will benefit photopharmacology in deep tissue.

An interesting electrocardiogram caused by lead reversal.

BACKGROUND: During normal sinus rhythm, atrial depolarization is conducted from right atrium to left atrium through Bachmann's bundle, and a normal P wave axis which is measured on the frontal plane is between 0º and + 75º. The change of P wave polarity is helpful for the analysis of origin point. CASE PRESENTATION: We report a patient with negative P wave in lead I. The characteristics of QRS complex in leads V1 to V6 are helpful to preliminarily differential diagnosis. The 12-lead electrocardiogram (ECG) with correct limb leads (right arm-left arm) placement shows sinus rhythm with complete right bundle branch block (RBBB). CONCLUSIONS: The change of P wave polarity as well as characteristics of QRS complex can help identify limb-lead reversals.

Rice rhizospheric effects and mechanism on soil cadmium bioavailability during silicon application.

Exogenous Si mitigates the mobility and bioavailability of Cd in the soil, thereby alleviating its phytotoxicity. This study focused on specific Si-induced immobilisation effects within the rhizosphere (S1), near-rhizosphere (S2), and far-rhizosphere (S3) zones. Based on the rhizobox experiment, we found that applying Si significantly elevated soil pH, and the variation amplitudes in the S3 soil exceeded those in the S1 and S2 soils. Si-induced changes in the rhizosphere also included enhanced dissolved organic carbon and diminished soil Eh, particularly in the Si400 treatment. Meanwhile, the introduction of Si greatly enhanced the Fe2+ and Mn2+ concentrations in the S1 soil, but reduced them in the S2 soil. The rhizosphere effect of Si which enriched Fe2+ and Mn2+ subsequently promoted the formation of Fe and Mn oxides/hydro-oxides near the rice roots. Consequently, the addition of Si significantly reduced the available Cd concentrations in S1, surpassing the reductions in S2 and S3. Moreover, Si-treated rice exhibited increased Fe plaque generation and fixation on soil Cd, resulting in decreased Cd concentrations in rice tissues, accompanied by reduced Cd translocation from roots to shoots and shoots to grains. Structural equation modelling further highlighted that Si is essential in Cd availability in S1 and Fe plaque development, ultimately mitigating Cd accumulation in rice. Si-treated rice also exhibited higher biomass and grain yield than those of control groups. These findings provide valuable insights into Si-based strategies for addressing the Cd contamination of agricultural soils.

Ionizable copolymer functionalized magnetic nanocomposite as an adsorbent for boosting the extraction selectivity of aristolochic acids.

Aristolochic acid nephropathy (AAN) has drawn increasing public attention. Organic anion transporters (OATs) are considered to be responsible for mediating nephrotoxicity of aristolochic acids (AAs), as AAs are typical OAT1 substrates that exhibit anionic properties and contain one hydrophobic domain. Inspired by the OAT1 three-dimensional structure or substrate/protein interactions involved in transport, we designed a magnetic polymeric hybrid, mimicking the effect of basic and aromatic residues of OAT1, for efficient enriching aristolochic acid I (AA I) and aristolochic acid II (AA II) in Traditional Chinese patent medicines (TCPM). N, N-dimethylaminopropyl acrylamide (DMAPAm) was used as a cationic monomer and copolymerized with divinylbenzene (DVB) onto the surface of monodisperse magnetic nanoparticles (denoted as MNs@SiO2T-DvbDam). The magnetic polymer hybrid demonstrated high selectivity and capacity for AAs, which was mainly attributed to (1) electrostatic interactions from the cationic or basic moiety of DMAPAm and (2) the hydrophobic and π-π stacking interactions from the aromatic ring of DVB. Additionally, the surface of the hybrid exhibited amphiphilic property according to the ionization of DMAPAm, thus improving the compatibility of the adsorbent with the aqueous sample matrix. This strategy was proven to be robust in the analysis of real drug samples, which was characterized by a good linearity, high recovery and satisfactory reusability. This work confirmed that the proposed tool could be a promising candidate for enhancing the extraction selectivity of AAs in Traditional Chinese medicines (TCM).

Radiation responsive PROTAC nanoparticles for tumor-specific proteolysis enhanced radiotherapy.

Proteolysis targeting chimeras (PROTACs) is a promising strategy for cancer therapy. However, the always-on bioactivity of PROTACs may lead to non-target toxicity, which restricts their antitumor performance. Here, we developed an X-ray radiation responsive PROTAC nanomicelle (RCNprotac) by covalently conjugating a reported small molecule PROTAC (MZ1) to hydrophilic PEG via a diselenide bond-containing carbon chain, which then self-assembled into a 141.80 ± 5.66 nm nanomicelle. The RCNprotac displayed no bioactivity during circulation due to the occupation of the hydroxyl group on the E3 ubiquitin ligand component and could effectively accumulate at the tumor site owing to the enhanced permeability and retention effect. Upon exposure to X-ray radiation, the radiation-sensitive diselenide bonds were broken to specifically release MZ1 for tumor BRD4 protein degradation. Furthermore, the reduction in the BRD4 protein level could increase the tumor's sensitivity to radiation. RCNprotac showed a synergistic enhancement of antitumor effects both in vitro and in vivo. We believe that this X-ray-responsive PROTAC nanomicelle could provide a new strategy for the X-ray-activated spatiotemporally controlled protein degradation and for the BRD4 proteolysis enhanced tumor radiosensitivity.

Anisotropic MXene/Poly(vinyl alcohol) Composite Hydrogels with Vertically Oriented Channels and Modulated Surface Topography for Efficient Solar-Driven Water Evaporation and Purification.

Hierarchical structure and surface topography play pivotal roles in developing high-performance solar-driven evaporators for clean water production; however, there exists a notable gap in research addressing simultaneous modulation of internal microstructure and surface topography in hydrogels to enhance both solar steam generation performance and desalination efficiency. Herein, anisotropic poly(vinyl alcohol)/MXene composite hydrogels for efficient solar-driven water evaporation and wastewater purification are fabricated using a template-assisted directional freezing approach followed by precise surface wettability modulation. The resultant composite hydrogels exhibit vertically oriented channels that ensure fast water supply during evaporation, and their poly(vinyl alcohol) skeletons can reduce the vaporization enthalpy of the water in the hydrogels. The incorporation of MXene sheets enables efficient solar light absorption and solar-thermal conversion while providing structural reinforcement to the hydrogels. More importantly, the as-created undulating solar-thermal surface, featuring modulated hydrophilic troughs and hydrophobic crests, significantly enhances solar-thermal conversion efficiency, thereby boosting solar evaporation performances. As a result, the fabricated hydrogel-based evaporator exhibits an impressive evaporation rate of 2.55 kg m-2 h-1 under 1 sun irradiation, coupled with long-term durability and desalination stability. Notably, the outstanding mechanical robustness of the hydrogel further enables high portability through a readily achievable process of reversible dehydration/hydration.

Low-Density Lipoprotein Cholesterol to Triglyceride Ratio and Clinical Outcomes after Acute Ischaemic Stroke or Transient Ischaemic Attack.

AIMS: Studies showed that low-density lipoprotein cholesterol (LDL-C) to triglyceride (TG) ratio could be used as a predictive parameter of low-density lipoprotein oxidation in vivo and the level of small dense LDL-C. However, whether LDL-C/TG ratio is associated with stroke prognosis remains unclear. We investigated the associations of LDL-C/TG ratio with outcomes in patients with acute ischaemic stroke (AIS) or transient ischaemic attacks (TIA) and explored whether it produced more predictive value than LDL-C and TG. METHODS: Data were derived from the Third China National Stroke Registry (CNSR-III). Multivariable Cox regression for stroke recurrence, composite vascular events and all-cause death and logistic regression for the poor functional outcome (modified Rankin Scale score 3-6) were used. RESULTS: A total of 14123 patients were included. After adjusting for confounding factors, quartile 4 of LDL-C/TG ratio was associated with an increased risk of recurrent stroke (hazard ratio [HR], 1.27; 95% confidence interval [CI], 1.03-1.56), composite vascular events (HR,1.23; 95% CI, 1.00-1.52), death (HR,1.70; 95% CI, 1.13-2.54) and poor functional outcome (odds ratio, 1.34; 95% CI, 1.12-1.61) at 3 months follow-up compared with quartile 1. We also found that quartile 4 of LDL-C and TG was positively and negatively associated with poor functional outcome at 3 months, respectively. LDL-C/TG ratio performed better than LDL-C or TG in predicting clinical outcomes. CONCLUSIONS: LDL-C/TG ratio was associated with the risk of stroke recurrence, composite vascular events, death and poor functional outcome in patients with AIS or TIA.

Melatonin is a potential novel analgesic agent for osteoarthritis: Evidence from cohort studies in humans and preclinical research in rats.

Melatonin exhibits potential for pain relief and long-term safety profile. We examined the analgesic effects of oral melatonin on osteoarthritis (OA) and investigated the underlying mechanism. Using data from a UK primary care database, we conducted a cohort study in individuals with OA to compare the number of oral analgesic prescriptions and the risk of knee/hip replacement between melatonin initiators and hypnotic benzodiazepines (i.e., active comparator) initiators using quantile regression models and Cox-proportional hazard models, respectively. To elucidate causation, we examined the effects of melatonin on pain behaviors and explored several metabolites that may serve as potential regulatory agents of melatonin in the monoiodoacetate rat model of OA. Using data from another community-based cohort study, that is, the Xiangya OA Study, we verified the association between the key serum metabolite and incident symptomatic knee OA. Compared with the hypnotic benzodiazepines cohort (n = 8135), the melatonin cohort (n = 813) had significantly fewer subsequent prescriptions of oral analgesics (50th percentile: 5 vs. 7, 75th percentile: 19 vs. 29, and 99th percentile: 140 vs. 162) and experienced a lower risk of knee/hip replacement (hazard ratio = 0.47, 95% Cl: 0.30-0.73) during the follow-up period. In rats, oral melatonin alleviated pain behaviors and increased serum levels of glycine. There was an inverse association between baseline serum glycine levels and the risk of incident symptomatic knee OA in humans (n = 760). In conclusion, our findings indicate that oral melatonin shows significant potential to be a novel treatment for OA pain. The potential role of glycine in its analgesic mechanism warrants further investigation.

Well-designed lamellar reduced graphene oxide-based foam for high-performance solar-driven water purification.

Although solar steam generation is promising for seawater desalination, it is less effective in purifying wastewater with both salt/heavy metal ions and organic contaminants. It is thus imperative to develop multifunctional integrated solar-driven water purification systems with high solar-thermal evaporation and photocatalytic degradation efficiencies. Herein, a lamellar reduced graphene oxide (L-RGO) foam with the vertical lamellar structure is fabricated by bidirectional-freezing, lyophilization, and slight chemical reduction for water purification. The unique vertical lamellar structure not only accelerates upward transport of water for facilitating water evaporation but also endows the L-RGO foam with superb high elasticity for tuning the interlayer distance and varying interactions between the oxygen-containing groups and water molecules to adjust water energy state. As a result, the L-RGO foam achieves a superb water evaporation rate of 2.40 kg m-2 h-1 along with an energy efficiency of 95.3 % under the compressive strain of 44.7 % under 1-sun irradiation. Equally importantly, the decoration of L-RGO foam with polypyrrole is capable of efficiently degrading organic pollutants while retaining high solar steam generation performances, exhibiting great potential in the comprehensive treatment of various water sources for relieving freshwater crisis.

Nutrition intake modifies the association between pulmonary function and cognitive performance among elderly Americans from NHANES 2011-2012.

PURPOSE: Nutrition intake is one of the modifiable risk factors for cognitive decline. Whether energy and protein intakes alter the association between pulmonary function (PF) and cognition has not been studied. METHODS: We made use of information from the U.S. National Health and Nutrition Examination Survey (NHANES) 2011-2012. PF measures, including forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and peak expiratory flow (PEF), were calculated, whereas cognitive function was assessed through four tests: the Immediate Recall test (IRT), the Delayed Recall test (DRT), the Animal Fluency test (AFT) and the Digit Symbol Substitution test (DSST). Energy and protein intakes were measured using the 24-h dietary recall method. Weighted generalized linear regression was performed upon adjustment for covariates. Further interaction analyses were conducted to investigate the effect of energy and protein intakes on the association between PF and cognition. RESULTS: We finally included 803 participants aged ≥ 60 years (54.4% female, weighted value). After adjusting for covariates, multiple measures (including FEV1, FVC, PEF, and composite PF) were all positively associated with better global cognition and the DSST score (P < 0.05). A stronger positive association between the DSST score and FEV1 (P for interaction = 0.001), FVC (P for interaction = 0.004), PEF (P for interaction = 0.003), and composite PF (P for interaction = 0.001) in lower energy intake. Similar results were observed in lower protein intake (all P for interaction < 0.05). CONCLUSION: Higher PF was independently associated with improved specific components of cognitive function (i.e., the DSST score). The positive association between PF and the DSST score was stronger in individuals with lower energy and protein intakes.

Age-related secretion of grancalcin by macrophages induces skeletal stem/progenitor cell senescence during fracture healing.

Skeletal stem/progenitor cell (SSPC) senescence is a major cause of decreased bone regenerative potential with aging, but the causes of SSPC senescence remain unclear. In this study, we revealed that macrophages in calluses secrete prosenescent factors, including grancalcin (GCA), during aging, which triggers SSPC senescence and impairs fracture healing. Local injection of human rGCA in young mice induced SSPC senescence and delayed fracture repair. Genetic deletion of Gca in monocytes/macrophages was sufficient to rejuvenate fracture repair in aged mice and alleviate SSPC senescence. Mechanistically, GCA binds to the plexin-B2 receptor and activates Arg2-mediated mitochondrial dysfunction, resulting in cellular senescence. Depletion of Plxnb2 in SSPCs impaired fracture healing. Administration of GCA-neutralizing antibody enhanced fracture healing in aged mice. Thus, our study revealed that senescent macrophages within calluses secrete GCA to trigger SSPC secondary senescence, and GCA neutralization represents a promising therapy for nonunion or delayed union in elderly individuals.

Myeloid-derived grancalcin instigates obesity-induced insulin resistance and metabolic inflammation in male mice.

The crosstalk between the bone and adipose tissue is known to orchestrate metabolic homeostasis, but the underlying mechanisms are largely unknown. Herein, we find that GCA + (grancalcin) immune cells accumulate in the bone marrow and release a considerable amount of GCA into circulation during obesity. Genetic deletion of Gca in myeloid cells attenuates metabolic dysfunction in obese male mice, whereas injection of recombinant GCA into male mice causes adipose tissue inflammation and insulin resistance. Mechanistically, we found that GCA binds to the Prohibitin-2 (PHB2) receptor on adipocytes and activates the innate and adaptive immune response of adipocytes via the PAK1-NF-κB signaling pathway, thus provoking the infiltration of inflammatory immune cells. Moreover, we show that GCA-neutralizing antibodies improve adipose tissue inflammation and insulin sensitivity in obese male mice. Together, these observations define a mechanism whereby bone marrow factor GCA initiates adipose tissue inflammation and insulin resistance, showing that GCA could be a potential target to treat metainflammation.

From pollution to solutions: Insights into the sources, transport and management of plastic debris in pristine and urban rivers.

River systems are important recipients of environmental plastic pollution and have become key pathways for the transfer of mismanaged waste from the land to the ocean. Understanding the sources and fate of plastic debris, including plastic litter (>5 mm) and microplastics (MPs) (<5 mm), entering different riverine systems is essential to mitigate the ongoing environmental plastic pollution crisis. We comprehensively investigated the plastic pollution in the catchments of two rivers in the Yangtze River basin: an urban river, the Suzhou section of the Beijing-Hangzhou Grand Canal (SZ); and a pristine rural river, the Jingmen section of the Hanjiang River (JM). The abundance of plastic pollutants in SZ was significantly higher than in JM: 0.430 ± 0.450 items/m3 and 0.003 ± 0.003 items/m3 of plastic litter in the water; 23.47 ± 25.53 n/m3 and 2.78 ± 1.55 n/m3 MPs in the water; and 218.82 ± 77.40 items/kg and 5.30 ± 1.99 items/kg of MPs in the sediment, respectively. Plastic litter and MPs were closely correlated in abundance and polymer composition. Overall, the polymer type, shape and color of MPs were dominant by polypropylene (42.5%), fragment (60.4%) and transparent (40.0%), respectively. Source tracing analysis revealed that packaging, shipping, and wastewater were the primary sources of plastic pollutants. The mantel analysis indicated that socio-economic and geospatial factors play crucial roles in driving the hotspot formation of plastic pollution in river networks. The composition of the MP communities differed significantly between the sediments and the overlying water. The urban riverbed sediments had a more pronounced pollutant 'sink' effect compared with the pristine rivers. These findings suggested that the modification of natural streams during urbanization may influence the transport and fate of plastic pollutants in them. Our results offer pivotal insights into effective preventive measures.

Research Progress on Replacement and Production Technology for Long-Distance Liquefied Ethane Pipelines.

Ethane is used as raw material to produce ethylene, which is the most important basic raw material for the petrochemical industry. The liquid phase ethane transportation method has the advantages of large transportation capacity and high economy. In this paper, the research progress of long-distance ethane pipelines is reviewed from the aspects of construction, phase change characteristics, standards and specifications, replacement, and production technology. The phase change characteristics of ethane-nitrogen mixed gas in the replacement process are discussed. In addition, the applicability of existing standards, specifications, and related replacement production technologies to liquefied ethane pipelines was analyzed, and operational recommendations have been given. Suggestions for future research are put forward to promote the application of pipeline replacement and production technology for ethane long transportation.

Gut-joint axis in knee synovitis: gut fungal dysbiosis and altered fungi-bacteria correlation network identified in a community-based study.

OBJECTIVES: Knee synovitis is a highly prevalent and potentially curable condition for knee pain; however, its pathogenesis remains unclear. We sought to assess the associations of the gut fungal microbiota and the fungi-bacteria correlation network with knee synovitis. METHODS: Participants were derived from a community-based cross-sectional study. We performed an ultrasound examination of both knees. A knee was defined as having synovitis if its synovium was ≥4 mm and/or Power Doppler (PD) signal was within the knee synovium area (PD synovitis). We collected faecal specimens from each participant and assessed gut fungal and bacterial microbiota using internal transcribed spacer 2 and shotgun metagenomic sequencing. We examined the relation of α-diversity, ß-diversity, the relative abundance of taxa and the interkingdom correlations to knee synovitis. RESULTS: Among 977 participants (mean age: 63.2 years; women: 58.8%), 191 (19.5%) had knee synovitis. ß-diversity of the gut fungal microbiota, but not α-diversity, was significantly associated with prevalent knee synovitis. The fungal genus Schizophyllum was inversely correlated with the prevalence and activity (ie, control, synovitis without PD signal and PD synovitis) of knee synovitis. Compared with those without synovitis, the fungi-bacteria correlation network in patients with knee synovitis was smaller (nodes: 93 vs 153; edges: 107 vs 244), and the average number of neighbours was fewer (2.3 vs 3.2). CONCLUSION: Alterations of gut fungal microbiota and the fungi-bacteria correlation network are associated with knee synovitis. These novel findings may help understand the mechanisms of the gut-joint axis in knee synovitis and suggest potential targets for future treatment.