SMPDL3A is a cGAMP-degrading enzyme induced by LXR-mediated lipid metabolism to restrict cGAS-STING DNA sensing.

Lipid metabolism has been associated with the cyclic guanosine monophosphate (GMP)-AMP synthase (cGAS) stimulator of interferon genes (STING) DNA-sensing pathway, but our understanding of how these signals are integrated into a cohesive immunometabolic program is lacking. Here, we have identified liver X receptor (LXR) agonists as potent inhibitors of STING signaling. We show that stimulation of lipid metabolism by LXR agonists specifically suppressed cyclic GMP-AMP (cGAMP)-STING signaling. Moreover, we developed cyclic dinucleotide-conjugated beads to biochemically isolate host effectors for cGAMP inhibition, and we found that LXR ligands stimulated the expression of sphingomyelin phosphodiesterase acid-like 3A (SMPDL3A), which is a 2'3'-cGAMP-degrading enzyme. Results of crystal structures suggest that cGAMP analog induces dimerization of SMPDL3A, and the dimerization is critical for cGAMP degradation. Additionally, we have provided evidence that SMPDL3A cleaves cGAMP to restrict STING signaling in cell culture and mouse models. Our results reveal SMPDL3A as a cGAMP-specific nuclease and demonstrate a mechanism for how LXR-associated lipid metabolism modulates STING-mediated innate immunity.

Association between multisite musculoskeletal pain and disability trajectories among community-dwelling older adults.

BACKGROUND: Pain is linked to disability, but how multisite musculoskeletal pain leads to disability over time is not well elaborated. OBJECTIVE: To examine the associations of multisite musculoskeletal pain with disability among a nationally representative cohort. DESIGN: We used data from the National Health and Aging Trends Study (NHATS) 2015-22. Disability was assessed by basic activities of daily living (ADL) and instrumental activities of daily living (IADL). PARTICIPANTS: A total of 5557 individuals with multisite musculoskeletal pain dwelling in the community were included in this study. METHODS: Group-based trajectory models were applied to identify distinct profiles of disability in ADL and IADL. Design-based logistic regressions were used to examine associations among multisite musculoskeletal pain, disability, and dual trajectory group memberships, adjusted for sociodemographic, health status, behavioral, and mental characteristics. RESULTS: Persons who experienced multisite musculoskeletal pain were at higher risk of disability in ADL and IADL. We identified five heterogeneous disability trajectories and named them based on baseline levels and rates of increase over time. Approximately, 52.42% of older adults with multisite musculoskeletal pain were in trajectories with ADL and IADL declines, and 33.60% experienced a rapid decline. Multisite musculoskeletal pain was associated with elevated relative risk for the adverse disability trajectories, which generally increases with multisite musculoskeletal pain frequency and number of sites. CONCLUSIONS: Persons with multisite musculoskeletal pain had a higher risk of disability. It is essential to adopt effective pain management strategies to maintain the independent living ability of older adults and to realize active aging.

Clinical prediction models for knee pain in patients with knee osteoarthritis: a systematic review.

OBJECTIVE: To identify and describe existing models for predicting knee pain in patients with knee osteoarthritis. METHODS: The electronic databases PubMed, EMBASE, CINAHL, Web of Science, and Cochrane Library were searched from their inception to May 2023 for any studies to develop and validate a prediction model for predicting knee pain in patients with knee osteoarthritis. Two reviewers independently screened titles, abstracts, and full-text qualifications, and extracted data. Risk of bias was assessed using the PROBAST. Data extraction of eligible articles was extracted by a data extraction form based on CHARMS. The quality of evidence was graded according to GRADE. The results were summarized with descriptive statistics. RESULTS: The search identified 2693 records. Sixteen articles reporting on 26 prediction models were included targeting occurrence (n = 9), others (n = 7), progression (n = 5), persistent (n = 2), incident (n = 1), frequent (n = 1), and flares (n = 1) of knee pain. Most of the studies (94%) were at high risk of bias. Model discrimination was assessed by the AUROC ranging from 0.62 to 0.81. The most common predictors were age, BMI, gender, baseline pain, and joint space width. Only frequent knee pain had a moderate quality of evidence; all other types of knee pain had a low quality of evidence. CONCLUSION: There are many prediction models for knee pain in patients with knee osteoarthritis that do show promise. However, the clinical extensibility, applicability, and interpretability of predictive tools should be considered during model development.

A Microlens Array Grating for Miniature Multi-Channel Spectrometers.

Most existing multi-channel spectrometers are constructed by physically stacking single-channel spectrometers, resulting in their large size, high weight, and limited number of channels. Therefore, their miniaturization is urgently needed. In this paper, a microlens array grating is designed for miniature multi-channel spectrometers. A transmissive element integrating microlens arrays and gratings, the MLAG, enables simultaneous focusing and dispersion. Using soft lithography, the MLAG was fabricated with a deviation of less than 2.2%. The dimensions are 10 mm × 10 mm × 4 mm with over 2000 available units. The MLAG spectrometer operates in the 400-700 nm wavelength range with a resolution of 6 nm. Additionally, the designed MLAG multi-channel spectrometer is experimentally verified to have independently valid cells that can be used in multichannel spectrometers. The wavelength position repeatability deviation of each cell is about 0.5 nm, and the repeatability of displacement measurements by the chromatic confocal sensor with the designed MLAG multi-channel spectrometer is less than 0.5 µm.

The Triterpenoids from Munronia pinnata and Their Anti-Proliferative Effects.

Six new tirucallane-type triterpenoids, named munropenes A-F (1-6), were extracted from the whole plants of Munronia pinnata using a water extraction method. Their chemical structures were determined based on detailed spectroscopic data. The relative configurations of the acyclic structures at C-17 of munropenes A-F (1-6) were established using carbon-proton spin-coupling constants (2,3JC,H) and inter-proton spin-coupling constants (3JH,H). Furthermore, the absolute configurations of munropenes A-F (1-6) were determined through high-performance liquid chromatography (HPLC), single-crystal X-ray diffraction, and electronic circular dichroism (ECD) analyses. The antiproliferative effects of munropenes A-F were evaluated in five tumor cell lines: HCT116, A549, HepG2, MCF7, and MDAMB. Munropenes A, B, D, and F (1, 2, 4, and 6) inhibited proliferation in the HCT116 cell line with IC50 values of 40.90, 19.13, 17.66, and 32.62 µM, respectively.

Structural insights revealed by crystal structure of B38-CAP, an isoenzyme of carboxypeptidase ACE2, the receptor of SARS-CoV-2.

The worldwide pandemic of Coronavirus disease 2019 (COVID-19) is triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and further worsened by the emergence of a variety of SARS-CoV-2 variants. Angiotensin-converting enzyme 2 (ACE2), a carboxypeptidase of M32 family, serves as the receptor of SARS-CoV-2 and key regulator of host renin-angiotensin system (RAS), both of which are mainly mediated via the carboxypeptidase domain of ACE2 (sACE2) or its activity. sACE2 is thus promising in the treatment of COVID-19 but unfortunately weakened by its unstrigent substrate preference and complex interplay with host RAS. B38-CAP, an isoenzyme of ACE2, partically compensates these defects but still encounters the problem related to carboxypeptidase activity and specificity. In this study, we firstly determined the crystal structure of B38-CAP at a resolution of 2.44 Å which exists in dimeric form with the non-crystallographic two-fold axis being in coincidence with the crystallographic two-fold axis. Further structural analysis revealed the structural conservatism feature among M32 family, particularly the catalytic core and moreover lead us to hypothesize that conformational flexibility might play an pivotal role in the catalysis of B38-CAP and ACE2. The work provided here presents key features of the M32 family carboxypeptidase and provides structural basis for further development of B38-CAP-based anti-SARS-CoV-2 drugs.

Key residues for maintaining architecture, assembly of plant hormone SA receptor NPR1.

Salicylic acid (SA) is a pivotal hormone required for the development of resistance to many pathogens in plants. As an SA receptor, NPR1(Nonexpressor of Pathogenesis-Related Genes 1) plays a key regulatory role in the plant immune response. The function of NPR1 is dependent on the alteration of its oligomer-to-monomer. Research in recent years has proven that NPRs perceive SA and regulate the expression of downstream defense genes, but the mechanism of NPR1 oligomer-to-monomer conversion remains unclear. In this paper, we mainly studied the oligomerization of NPR1. By mutation experiments on some residues in the BTB domain involved in protein interactions, we found that the residue His80 plays a key role in the oligomerization of NPR1. We also found that NPR1, interacting with zinc ions at a ratio close to 1:1, was independent of the residue His80. These findings may help us to understand the conformational conversion of NPR1.

Enterovirus D68 Protease 2Apro Targets TRAF3 To Subvert Host Innate Immune Responses.

Human enterovirus D68 (EV-D68) has received considerable attention recently as a global reemergent pathogen because it causes severe respiratory tract infections and acute flaccid myelitis (AFM). The nonstructural protein 2A protease (2Apro) of EVs, which functions in the cleavage of host proteins, comprises a pivotal part of the viral immune evasion process. However, the pathogenic mechanism of EV-D68 is not fully understood. In this study, we found that EV-D68 inhibited antiviral type I interferon responses by cleaving tumor necrosis factor receptor-associated factor 3 (TRAF3), which is the key factor for type I interferon production. EV-D68 inhibited Sendai virus (SEV)-induced interferon regulatory factor 3 (IRF3) activation and beta interferon (IFN-ß) expression in HeLa and HEK293T cells. Furthermore, we demonstrated that EV-D68 and 2Apro were able to cleave the C-terminal region of TRAF3 in HeLa and HEK293T cells, respectively. A cysteine-to-alanine substitution at amino acid 107 (C107A) in the 2Apro protease resulted in the loss of cleavage activity to TRAF3, and mutation of glycine at amino acid 462 to alanine (G462A) in TRAF3 conferred resistance to 2Apro These results suggest that control of TRAF3 by 2Apro may be a mechanism EV-D68 utilizes to subvert host innate immune responses.IMPORTANCE Human enterovirus 68 (EV-D68) has received considerable attention recently as a global reemergent pathogen because it causes severe respiratory tract infections and acute flaccid myelitis. The nonstructural protein 2A protease (2Apro) of EV, which functions in cleavage of host proteins, comprises an essential part of the viral immune evasion process. However, the pathogenic mechanism of EV-D68 is not fully understood. Here, we show for the first time that EV-D68 inhibited antiviral type I interferon responses by cleaving tumor necrosis factor receptor-associated factor 3 (TRAF3). Furthermore, we identified the key cleavage site in TRAF3. Our study may suggest a new mechanism by which the 2Apro of EV facilitates subversion of host innate immune responses. These findings increase our understanding of EV-D68 infection and may help identify new antiviral targets against EV-D68.

Determinants of depressive symptom trajectories in self-reported chronic obstructive pulmonary disease patients.

BACKGROUND: The depressive symptom trajectories of COPD individuals and its' predictors remain to be established. Therefore, this study aimed to explore the trajectories of depressive symptoms and predictors thereof in COPD patients. METHODS: A total of 1286 individuals over 45 years of age with self-reported COPD were assessed. Depressive symptoms were evaluated using the Center for Epidemiological Studies Depression Scale short form, with depressive symptom trajectories being identified via latent class growth analysis. The predictors of depressive symptom trajectories were then identified through multinomial logistic regression. RESULTS: Finally, three depressive symptom trajectories were identified: "steadily high", "consistently moderate", and "consistently low". Old age, longer night-time sleep duration, and high BMI were found to be associated with individuals being classified under the "consistently moderate" trajectory. Moreover, participants exhibiting more than two chronic conditions were more likely to be classified under the "consistently moderate" trajectory. Higher education and lower hand grip strength were important predictors of individuals classified in the "steadily high" trajectory. CONCLUSIONS: To conclude, three depressive symptom trajectories were identified in self-reported COPD individuals. To ensure timely intervention aimed at preventing the worsening of depressive symptom progression among COPD individuals, health-care workers should regular analyze depressive symptoms and provide appropriate interventions when possible.

Au-NPs signal amplification ultra-sensitivity optical microfiber interferometric biosensor.

An optical microfiber interferometric biosensor for the low concentration detection of sequence-specific deoxyribonucleic acid (DNA) based on signal amplification technology via oligonucleotides linked to gold nanoparticles (Au-NPs) is proposed and experimentally analyzed. The sensor uses a "sandwich" detection strategy, in which capture probe DNA (DNA-c) is immobilized on the surface of the optical microfiber interferometer, the reporter probe DNA (DNA-r) is immobilized on the surface of Au-NPs, and the DNA-c and DNA-r are hybridized to the target probe DNA (DNA-t) in a sandwich arrangement. The dynamic detection of the DNA-t was found to range from 1.0×10-15 M to 1.0×10-8 M, and the limit of detection (LOD) concentration was 1.32 fM. This sensor exhibited not only a low LOD but also excellent selectivity against mismatched DNA-t, and it can be further developed for application in various sensing platforms.

Bamboo-like microfiber structures fabricated by one-step-tapering a fiber preform.

The microfiber-based optical structures have been attracting increasing research interests in communications and sensing fields. However, the fabrication of forming structures on fragile microfibers requires delicate operations, which limits the developments of their practical applications. In this work, a one-step-tapering technique is proposed to manufacture structures on microfibers. As a demonstration, the fiber preform, consisting of sawtooth shaped solid-air interfaces with designed dimensions, is obtained using a femtosecond laser milling technique. By one-step tapering the preform, periodic bumps are formed, resulting in a bamboo-like microfiber device. The fabricated structure shows spectral characteristics of a long-period grating, of which extinction ratio is up to 18.2 dB around 1553.3 nm. The response to refractive index is measured to be ∼875.02 nm/RIU and the temperature coefficient is ∼5.78 pm/°C. The theoretical analysis shows good agreement with the experimental results. The microfiber-based structure fabricated using the one-step-tapering-preform technique is featured with flexibility of design, reproducibility, and structural stability.

Advances in Studies on Toxic Effects of Short-Chain Chlorinated Paraffins (SCCPs) and Characterization of Environmental Pollution in China.

Short-chain chlorinated paraffins (SCCPs) were included in the Stockholm Convention in 2017. SCCPs have persistence, bioaccumulation, long-range environmental mobility and biological toxicity, significant toxicity to aquatic organisms, and potential carcinogenicity. Little study was on the progress research on the current environmental pollution in China. We reviewed the pollution conditions of SCCPs in air, soil, and water and their accumulation in food and organisms in China, especially for the contaminations of aquatic ecosystem. Meanwhile, we summarize the recent studies on the toxic effects and toxicological mechanisms of SCCPs on aquatic organisms and mammals. Finally, the further direction and trends for SCCP research were proposed. More efforts are necessary to conduct a comprehensive risk assessment and evaluate the relative importance of the various exposure routes.

Research Progress on Toxic Effects and Water Quality Criteria of Triclosan.

Triclosan (TCS) is an effective broad-spectrum antimicrobial agent that is widely used in personal care products. It has been detected in different environmental media, and poses high potential ecological risk. In this article, we carried out a literature review of recent studies on the toxic effects of TCS from different aspects at the molecular, cell, tissue, organ, and individual level. TCS can exhibit acute toxicity to aquatic organisms, affect the normal expression and physiological function of enzymes and genes, and produce cytotoxicity. Many studies have demonstrated that TCS exerts significant endocrine-disrupting effects on organisms, interfering the normal physiological functions of the reproductive, thyroid, and nervous systems via related signaling pathways. Moreover, we reported current research on the water quality criteria of TCS and discuss possible future research directions.

Cluster-Induced Deagglomeration in Dilute Gravity-Driven Gas-Solid Flows of Cohesive Grains.

Clustering is often presumed to lead to enhanced agglomeration between cohesive grains due to the reduced relative velocities of particles within a cluster. Our discrete-particle simulations on gravity-driven, gas-solid flows of cohesive grains exhibit the opposite trend, revealing a new mechanism we coin "cluster-induced deagglomeration." Specifically, we examine relatively dilute gas-solid flows and isolate agglomerates of cohesive origin from overall heterogeneities in the system, i.e., agglomerates of cohesive origin and clusters of hydrodynamic origin. We observe enhanced clustering with an increasing system size (as is the norm for noncohesive systems) as well as reduced agglomeration. The reduced agglomeration is traced to the increased collisional impact velocities of particles at the surface of a cluster; i.e., higher levels of clustering lead to larger relative velocities between the clustered and nonclustered regions, thereby serving as an additional source of granular temperature. This physical picture is further evidenced by a theoretical model based on a balance between the generation and breakage rates of agglomerates. Finally, cluster-induced deagglomeration also provides an explanation for a surprising saturation of agglomeration levels in gravity-driven, gas-solid systems with increasing levels of cohesion, as opposed to the monotonically increasing behavior seen in free-evolving or driven granular systems in the absence of gravity. Namely, higher cohesion leads to more energy dissipation, which is associated with competing effects: enhanced agglomeration and enhanced clustering, the latter of which results in more cluster-induced deagglomeration.

Catalyst free hydrazone ligation for protein labeling and modification using electron-deficient benzaldehyde reagents.

Bioorthogonal reactions have emerged as valuable tools for site-specific protein labeling and modification in vitro and in vivo. Hydrazone and oxime ligation has recently attracted considerable attention for wide applications in the conjugation of biomolecules. However, this kind of reaction has suffered from slow kinetics under physiological conditions and toxicity or complications of the reaction system due to catalysts. In this work we have developed an electron-deficient benzaldehyde reagent, which can be easily equipped with various types of bio-functional molecules for catalyst-free hydrazone ligation. The reagent can be equipped with not only small molecules such as fluorescence dyes or drugs, but also macromolecules like PEG. These can be precisely ligated to the C-terminus of proteins by an efficient hydrazone reaction at neutral pH and room temperature. The new reagent based catalyst-free hydrazone ligation provides a practical approach for the site specific modification of proteins.

[Treatment of Recurrent Oral Ulceration (Yin Deficiency Fire Excess Type) by Qianjin Kouchuang Jiawei Granule: a Clinical Observation].

OBJECTIVE: To observe the curative effect of Qianjin Kouchuang Jiawei Granule (QKJG) on recurrent oral ulceration [yin deficiency fire excess type (YDFET)]. METHODS: Totally 120 patients who suffered from recurrent oral ulceration (YDFET) were randomly assigned to two groups, the experiment group and the control group, 60 in each group. Patients in the experiment group took QKJG, 20 g each time, twice per day, while those in the control group took Kouyanqing Granule (KG) , 20 g each time, twice per day. Fourteen days consisted of one therapeutic course, two for all. Scores for patients' symptoms and signs (ulcer area, exudation, hyperaemia, edema, the number of ulceration, burning sensation, and pain degrees) were assessed before treatment, at day 3 and 7 after treatment. Short-term efficacy was assessed by visual analogue scale (VAS). The total paralysis time and the total number of ulceration at month 12 after treatment were taken as judgment for long-term efficacy. Results Compared with before treatment in the same group, symptoms and signs were obviously improved at day 3 and 7 after treatment in the two groups (P < 0.05). Compared with the control group at day 3 after treatment, the improvement of edema, exudation, pain degree, and burning sensation was more obvious in the experiment group (P < 0.05, P < 0.01). The improvement of edema, pain degree, and burning sensation at day 7 after treatment was more obvious in the experiment group than in the control group (P < 0.05). As for short-term efficacy, the total effective rate was 86.67% (52/60 cases) in the experiment group and 83.33% (50/60 cases) in the control group, with no statistical difference between the two groups (P > 0.05). As for long-term efficacy, the total effective rate was 90.00% (54/60 cases) in the experiment group, significantly higher than that of the control group with statistical difference [81.67% (49/60 cases), P < 0.05]. At month 12 after treatment, the total number of ulceration was reduced and the paralysis time of ulcer attack prolonged in the experiment group, with statistical difference when compared with the control group (P < 0.05). CONCLUSION: QKJG showed better long-term efficacy than that of KG in treating recurrent oral ulceration (YDFET).

Arbuscular Mycorrhizal Fungi Diversity in Sophora japonica Rhizosphere at Different Altitudes and Lithologies.

Arbuscular mycorrhizal fungi play a key role in mediating soil-plant relationships within karst ecosystems. Sophora japonica, a medicinal plant with anti-inflammatory and antitumor properties, is widely cultivated in karst areas of Guangxi, China. We considered limestone, dolomite, and sandstone at altitudes ranging from 100 to 800 m and employed Illumina sequencing to evaluate AMF diversity and identify the factors driving S. japonica rhizosphere AMF community changes. We showed that the increase in altitude increased S. japonica AMF colonization and the Shannon index. The colonization of limestone plots was higher than that of other lithology. In total, 3,096,236 sequences and 5767 OTUs were identified in S. japonica rhizosphere soil. Among these, 270 OTUs were defined at the genus level and divided into 7 genera and 35 species. Moreover, available nitrogen, soil organic matter, and available calcium content had a coupling effect and positive influence on AMF colonization and Shannon and Chao1 indices. Conversely, available phosphorus, available potassium, and available magnesium negatively affected AMF Shannon and Chao1 indices. Lithology, altitude, pH, and available phosphorus are important factors that affect the dynamics of AMF in the S. japonica rhizosphere.

Association of body composition and physical activity with pain and function in knee osteoarthritis patients: a cross-sectional study.

OBJECTIVE: The objective of this study is to delineate disparities between patients with knee osteoarthritis (KOA) based on obesity status, investigate the interplay among body composition, physical activity and knee pain/function in patients with KOA and conduct subgroup analyses focusing on those with KOA and obesity. DESIGN: Cross-sectional study. SETTING: Residents of eight communities in Shijiazhuang, Hebei Province, China, were surveyed from March 2021 to November 2021. PARTICIPANTS: 178 patients with symptomatic KOA aged 40 years or older were included. MAIN OUTCOMES AND MEASURES: The primary outcome measure was knee pain, assessed using the Western Ontario and McMaster Universities Osteoarthritis Index-pain (WOMAC-P) scale. Secondary outcome measures included function, evaluated through the WOMAC-function (WOMAC-F) scale and the Five-Time-Sit-to-Stand Test (FTSST). Data analysis involved t-tests, Wilcoxon rank-sum tests, χ2 tests, linear and logistical regression analysis. RESULTS: Participants (n=178) were 41-80 years of age (median: 65, P25-P75: 58-70), and 82% were female. Obese patients (n=103) had worse knee pain and self-reported function (p<0.05). In general patients with KOA, body fat mass was positively associated with bilateral knee pain (ß=1.21 (95% CI 0.03 to 0.15)), WOMAC-P scores (ß=0.25 (95% CI 0.23 to 1.22)), WOMAC-F scores (ß=0.28 (95% CI 0.35 to 1.29)) and FTSST (ß=0.19 (95% CI 0.03 to 0.42)), moderate-intensity to low-intensity physical activity was negatively associated with bilateral knee pain (ß=-0.80 (95% CI -0.10 to -0.01)) and Skeletal Muscle Index (SMI) was negatively associated with WOMAC-F scores (ß=-0.16 (95% CI -0.66 to -0.03)). In patients with KOA and obesity, SMI was negatively associated with FTSST (ß=-0.30 (95% CI -3.94 to -0.00)). CONCLUSION: Patients with KOA and obesity had worse knee pain and self-reported function compared with non-obese patients. Greater fat mass, lower muscle mass and lower moderate-intensity to low-intensity physical activity were associated with increased knee pain and poor self-reported function. More skeletal muscle mass was associated with the improvement of objective function.

Metal chalcogenide nanorings for temperature-strain dual-mode sensing.

Most metal chalcogenides exhibit layered structures and anisotropic morphologies such as nanosheets, nanoplates, and nanotubes, as well as nanosheet-assembled nanoflowers. Unconventional morphologies such as nanorings may bring appealing properties to functional materials, but they have not been realized with metal chalcogenides. Herein, we report that Sn0.2Mo0.8S2 nanorings with a mixed 1T/2H phase were synthesized by etching SnS2 cores from Sn1-xMoxS2/SnS2 lateral heterostructures. Flexible electronic sensors based on these Sn0.2Mo0.8S2 nanorings exhibited excellent temperature and strain sensing performance, with a negative temperature coefficient of resistance of -0.013 °C-1 and a minimum detectable strain of 0.09%. In addition, the dual-functional flexible electronic sensors with easy fabrication and good wearability showed great promise for tracking human activities and monitoring inapparent health-related signals.

Development of a nomogram prediction model for gait speed trajectories in persons with knee osteoarthritis.

To examine heterogeneous trajectories of 8-year gait speed among patients with symptomatic knee osteoarthritis (KOA) and to develop a nomogram prediction model. We analyzed data from the Osteoarthritis Initiative (OAI) assessed at baseline and follow-up over 8 years (n = 1289). Gait speed was measured by the 20-m walk test. The gait speed trajectories among patients with KOA were explored by latent class growth analysis. A nomogram prediction model was created based on multivariable logistic regression. Three gait speed trajectories were identified: the fast gait speed group (30.4%), moderate gait speed group (50.5%) and slow gait speed group (19.1%). Age ≥ 60 years, female, non-white, nonmarried, annual income < $50,000, obesity, depressive symptoms, comorbidity and WOMAC pain score ≥ 5 were risk factors for the slow gait trajectory. The area under the ROC curve of the prediction model was 0.775 (95% CI 0.742-0.808). In the external validation cohort, the AUC was 0.773 (95% CI 0.697-0.848). Heterogeneous trajectories existed in the gait speed of patients with KOA and could be predicted by multiple factors. Risk factors should be earlier identified, and targeted intervention should be carried out to improve physical function of KOA patients.