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The Atlantic salmon is an extremely popular fish for its nutritional value and unique taste among several fish species. Researchers are focusing on the utilization of Atlantic salmon waste for generating protein hydrolysates rich in peptides and amino acids and investigating their health benefits. Several technological approaches, including enzymatic, chemical, and the recently developed subcritical water hydrolysis, are currently used for the production of Atlantic salmon waste protein hydrolysates. Hydrolyzing various wastes, e.g., heads, bones, skin, viscera, and trimmings, possessing antioxidant, blood pressure regulatory, antidiabetic, and anti-inflammatory properties, resulting in applications in human foods and nutraceuticals, animal farming, pharmaceuticals, cell culture, and cosmetics industries. Furthermore, future applications, constraints several challenges associated with industrial hydrolysate production, including sensory, safety, and economic constraints, which could be overcome by suggested techno processing measures. Further studies are recommended for developing large-scale, commercially viable production methods, focusing on eradicating sensory constraints and facilitating large-scale application.

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A novel sub-class of S-adenosyl-l-methionine (SAM)-dependent methyltransferases catalyze atypical chemical transformations in the biosynthesis of anthracyclines. Exemplified by RdmB from Streptomyces purpurascens, it was found with 10-decarboxylative hydroxylation activity on anthracyclines. We herein investigated the catalytic activities of RdmB and discovered a previously unknown 4-O-methylation activity. The site-directed mutagenesis studies proved that the residue at position R307 and N260 are vital for the decarboxylative hydroxylation and 4-O-methylation, respectively, which define two distinct catalytic centers in RdmB. Furthermore, the multifunctionality of RdmB activity was found as cofactor-dependent and stepwise. Our findings expand the versatility and importance of methyltransferases and should aid studies to enrich the structural diversity and bioactivities of anthracyclines.

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JOURNAL/nrgr/04.03/01300535-202508000-00026/figure1/v/2024-09-30T120553Z/r/image-tiff Interferon regulatory factor 7 plays a crucial role in the innate immune response. However, whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown. Here we report that interferon regulatory factor 7 is markedly up-regulated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease and co-localizes with microglial cells. Both the selective cyclic guanosine monophosphate adenosine monophosphate synthase inhibitor RU.521 and the stimulator of interferon genes inhibitor H151 effectively suppressed interferon regulatory factor 7 activation in BV2 microglia exposed to 1-methyl-4-phenylpyridinium and inhibited transformation of mouse BV2 microglia into the neurotoxic M1 phenotype. In addition, siRNA-mediated knockdown of interferon regulatory factor 7 expression in BV2 microglia reduced the expression of inducible nitric oxide synthase, tumor necrosis factor α, CD16, CD32, and CD86 and increased the expression of the anti-inflammatory markers ARG1 and YM1. Taken together, our findings indicate that the cyclic guanosine monophosphate adenosine monophosphate synthase-stimulator of interferon genes-interferon regulatory factor 7 pathway plays a crucial role in the pathogenesis of Parkinson's disease.

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Two coordination polymers (CPs), [Zn5(L)2(phen)5](1) and [Cd2(HL)(2,2-bpy)(H2O)3](2), were synthesized by using 2',3,3',5,5'-Diphenyl ether pentacarboxylic acid (H5L), phenanthroline (phen), and 2,2'-bipyridine (2,2'-bpy) under hydrothermal conditions. The L5- ligand adopts the µ6-к2: к2: к1: к1: к1: к1 mode in 1 and the µ5-к2: к2: к2: к2: к1 mode in 2. Sensing experiments show that 1 and 2 are fluorescence probes with high sensitivity and rapid detection of nitro explosives, antibiotics, and pesticides. In order to verify the ability of 2 to detect FLU in actual samples, we performed a spiked recovery experiment in green pepper water. The spiked recoveries were 97.77-101.18 %. Interestingly, because H5L is not completely deprotonated in 2, there is abundant hydrogen bonding, which makes the fluorescence quenching rate higher and the detection limit lower. The possible fluorescence quenching mechanism of 1 and 2 can be explained by their UV-VIS absorption spectra and orbital energy levels.

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To investigate the seasonal characteristics in air pollution in Chengdu, a single particle aerosol mass spectrometry was used to continuously observe atmospheric fine particulate matter during one-month periods in summer and winter, respectively. The results showed that, apart from O3, the concentrations of other pollutants (CO, NO2, SO2, PM2.5 and PM10) were significantly higher in winter than in summer. All single particle aerosols were divided into seven categories: biomass burning (BB), coal combustion (CC), Dust, vehicle emission (VE), K mixed with nitrate (K-NO3), K mixed with sulfate and nitrate (K-SN), and K mixed with sulfate (K-SO4) particles. The highest contributions in both seasons were VE particles (24%). The higher contributions of K-SO4 (16%) and K-NO3 (10%) particles occurred in summer and winter, respectively, as a result of their different formation mechanisms. S-containing (K-SO4 and K-SN), VE, and BB particles caused the evolution of pollution in both seasons, and they can be considered as targets for future pollution reduction. The mixing of primary sources particles (VE, Dust, CC, and BB) with secondary components was stronger in winter than in summer. In summer, as pollution worsens, the mixing of primary sources particles with 62 [NO3]- weakened, but the mixing with 97 [HSO4]- increased. However, in winter, the mixing state of particles did not exhibit an obvious evolution rules. The potential source areas in summer were mainly distributed in the southern region of Sichuan, while in winter, besides the southern region, the contribution of the western region cannot be ignored.

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OBJECTIVE: The study aimed to develop a model to predict the risk of sarcopenia in gastrointestinal cancer patients. The goal was to identify these patients early and classify them into different risk categories based on their likelihood of developing sarcopenia. METHODS: This study evaluated risk factors for sarcopenia in patients with gastrointestinal cancers through a systematic review and meta-analysis. The natural logarithm of the combined risk estimate for each factor was used as a coefficient to assign scores within the model for risk prediction. Data from 270 patients with gastrointestinal cancers, collected between October 2023 and April 2024, was used to assess the predictive performance of the scoring model. RESULTS: The analysis included 17 studies that included 9405 patients with gastrointestinal cancers, out of which 4361 had sarcopenia. The model identified several significant predictors of sarcopenia, including age (OR = 2.45), sex (OR = 1.15), combined diabetes (OR = 2.02), neutrophil-to-lymphocyte ratio (NLR) category (OR = 1.61), TNM stage (OR = 1.61), and weight change (OR = 1.60). Model validation was performed using an external cohort through logistic regression, resulting in an area under the curve (AUC) of 0.773. This model attained a sensitivity of 0.714 and a specificity of 0.688 and ultimately selected 16.5 as the ideal critical risk score. Furthermore, an AUC of 0.770 was obtained from Bayesian model validation; the optimal critical risk score was determined to be 19.0, which corresponds to a sensitivity of 0.658 and a specificity of 0.847. CONCLUSIONS: The model of risk prediction developed through systematic review and meta-analysis demonstrates substantial for sarcopenia in patients with gastrointestinal cancers. Its clinical usability facilitates the screening of patients at high risk for sarcopenia.

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Osteoarthritis (OA) is the most common joint disease with high prevalence and incidence. Increasing reports has indicated that circular RNAs (circRNAs) are implicated in OA progression. Nevertheless, the roles and functions of most circRNAs in OA remain to be elucidated. In this study, we emphatically discussed circ-IQGAP1 (circ_0104873) in OA. Firstly, we discovered that circ_0104873 was dramatically overexpressed during osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Several functional assays demonstrated that circ_0104873 inhibition repressed BMSCs proliferation and osteogenic differentiation. Moreover, mechanism assays also revealed that circ_0104873 sponged microRNA-875-5p (miR-875-5p) to up-regulate notch receptor 3 (NOTCH3), thereby activating the Notch signaling pathway. Rescue assays disclosed that circ_0104873 contributed to the development of OA via targeting miR-875-5p/NOTCH3 axis. In conclusion, circ_0104873 promoted the progression of OA by miR-875-5p/NOTCH3/Notch signaling pathway, which might provide a promising target for OA treatment.

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This study constructed a system dynamics (SD) evolutionary game model, from which we analyzed the conditions that need to be met by multi-agents to achieve cooperation in agricultural water conservancy (AWC) Public-Private Partnership (PPP) projects. Simultaneously, this study used numerical simulation to depict the impact of initial participation willingness, reward, punishment, income, and other parameters of local governments, project enterprises, and farmers on the evolution strategy. The results firstly showed that the basic conditions for tripartite cooperation are to strengthen the rewards and punishments for project enterprises and improve the participation benefits of farmers. Secondly, it showed that increasing the rewards for farmers and improving the project dividend benefits can effectively motivate farmers to participate. Thirdly, it showed that enhancing the incentive subsidies and reputation benefits for project enterprise's participation, as well as strengthening the supervision of local government, boosts the motivation of project enterprises significantly. However, it is vital to ensure that the reward amounts are not too high to allow local government to play its guiding role efficiently. Lastly, the results indicated that digital technology can help reduce the participation cost of local government, project enterprises and farmers, and improve the external reputation benefits of each participant, thus forming a win-win situation for all three participants. Analyzing the cooperation strategies of the three parties in AWC PPP projects provides theoretical support and a decision-making basis for the efficient operation of AWC PPP projects under the digital background, and also provides practical policy recommendations for the high-quality development of AWC.

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Reference electrode (RE) plays the core role in accurate potential control in electrochemistry. However, nanoresolved electrochemical characterization techniques still suffer from unstable potential control of pseudo-REs, because the commercial RE is too large to be used in the tiny electrochemical cell, and thus only pseudo-RE can be used. Therefore, microsized RE with a stable potential is urgently required to push the nanoresolved electrochemical measurements to a new level of accuracy and precision, but it is quite challenging to reproducibly fabricate such a micro RE until now. Here, we revisited the working mechanism of the metal-junction RE and clearly revealed the role of the ionic path between the metal wire and the borosilicate glass capillary to maintain a stable potential of RE. Based on this understanding, we developed a method to fabricate micro ultrastable-RE, where a reproducible ultrathin ionic path can form by dissolving a sandwiched sacrificial layer between the Pt wire and the capillary for the ion transfer. The potential of this new micro RE was almost the same as that of the commercial Ag/AgCl electrode, while the size is much smaller. Different from commercial REs that must be stored in the inner electrolyte, the new RE could be directly stored in air for more than one year without potential drift. Eventually, we successfully applied the micro RE in the electrochemical tip-enhanced Raman spectroscopy (EC-TERS) measurement to precisely control the potential of the working electrode, which makes it possible to compare the results from different laboratories and techniques to better understand the electrochemical interface at the nanoscale.

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To achieve chiral amplification, life uses small chiral molecules as building blocks to construct hierarchical chiral architectures that can realize advanced physiological functions. Inspired by the chiral amplification strategy of nature, we herein demonstrate that the chiral assembly of chiral gold nanorods (GNRs) leads to enhanced optical asymmetry factors (g-factors), up to 0.24. The assembly of chiral GNRs, dictated by structural self-matching, leads to g-factors with over 100-fold higher values than those of individual chiral GNRs, as confirmed by numerical simulations. Moreover, the efficient optical asymmetry of chiral GNR assemblies enables their application as highly sensitive sensors of adenosine triphosphate (ATP detection limit of 1.0 µM), with selectivity against adenosine diphosphate and adenosine monophosphate.

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BACKGROUND: Peristomal skin complications (PSCs) are the most common complication among patients with ostomies after ostomy creation. PURPOSE: This systematic review and meta-analysis aimed to evaluate the factors influencing the occurrence of peristomal skin complications. METHODS: A systematic review was conducted across multiple databases by using a combination of subject terms and free words for online search. The databases were searched from their inception to October 31, 2023. All studies that met inclusion criteria were examined to identify risk factors for PSCs. Two researchers independently conducted literature screening and information extraction, evaluated the literature quality using the Newcastle-Ottawa Scale, and performed descriptive analysis of the results. RESULTS: Ten studies were included in this review. A total of 3753 patients with ostomies participated in the studies, and 981 patients suffered from PSCs, with PSC incidence ranging from 15.5% to 47.7%. Type of ostomy, diabetes, self-care knowledge, and chemotherapy were significant factors associated with PSCs. CONCLUSION: This review highlighted 4 factors that influence the occurrence of peristomal skin complications. The quality of included literature is generally low, with significant heterogeneity in study design and choice of outcome indicators. Therefore, further research involving high-quality studies with larger sample sizes is needed for deeper investigation.

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BACKGROUND: Multiple system atrophy (MSA) is recognized as an atypical Parkinsonian syndrome, distinguished by a more rapid progression than that observed in Parkinson's disease. Unfortunately, the prognosis for MSA remains poor, with a notable absence of globally recognized effective treatments. Although preliminary studies suggest that transcranial magnetic stimulation (TMS) could potentially alleviate clinical symptoms in MSA patients, there is a significant gap in the literature regarding the optimal stimulation parameters. Furthermore, the field lacks consensus due to the paucity of robust, large-scale, multicenter trials. METHODS: This investigation is a multi-center, randomized, double-blind, sham-controlled trial. We aim to enroll 96 individuals diagnosed with MSA, categorized into Parkinsonian type (MSA-P) and cerebellar type (MSA-C) according to their predominant clinical features. Participants will be randomly allocated in a 1:1 ratio to either the TMS or sham stimulation group. Utilizing advanced navigation techniques, we will ensure precise targeting for the intervention, applying theta burst stimulation (TBS). To assess the efficacy of TBS on both motor and non-motor functions, a comprehensive evaluation will be conducted using internationally recognized clinical scales and gait analysis. To objectively assess changes in brain connectivity, functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) will be employed as sensitive indicators before and after the intervention. DISCUSSION: The primary aim of this study is to ascertain whether TBS can alleviate both motor and non-motor symptoms in patients with MSA. Additionally, a critical component of our research involves elucidating the underlying mechanisms through which TBS exerts its potential therapeutic effects. ETHICS AND DISSEMINATION: All study protocols have been reviewed and approved by the First Affiliated Medical Ethics Committee of the Air Force Military Medical University (KY20232118-F-1). TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300072658. Registered on 20 June 2023.

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Vascularization is a major challenge in the field of tissue engineering and regenerative medicine. Mechanical factors have been demonstrated to play a fundamental role in vasculogenesis and angiogenesis and can affect the architecture of the generated vascular network. Through the regulation of mechanical factors in engineered tissues, various mechanical strategies can be used to optimize the preformed vascular network and promote its rapid integration with host vessels. Optimization of the mechanical properties of scaffolds, including controlling scaffold stiffness, increasing surface roughness and anisotropic structure, and designing interconnected, hierarchical pore structures, is beneficial for the in vitro formation of vascular networks and the ingrowth of host blood vessels. The incorporation of hollow channels into scaffolds promotes the formation of patterned vascular networks. Dynamic stretching and perfusion can facilitate the formation and maturation of preformed vascular networks in vitro. Several indirect mechanical strategies provide sustained mechanical stimulation to engineered tissues in vivo, which further promotes the vascularization of implants within the body. Additionally, stiffness gradients, anisotropic substrates and hollow channels in scaffolds, as well as external cyclic stretch, boundary constraints and dynamic flow culture, can effectively regulate the alignment of vascular networks, thereby promoting better integration of prevascularized engineered tissues with host blood vessels. This review summarizes the influence and contribution of both scaffold-based and external stimulus-based mechanical strategies for vascularization in tissue engineering and elucidates the underlying mechanisms involved.

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INTRODUCTION/OBJECTIVE: This study aimed to examine the effect of a human umbilical cord mesenchymal stem cell-derived exosome (hUC-MSC-Exo) liquid band-aid on wound healing in mice. METHODS: hUC-MSC-Exos were prepared from the supernatant via ion exchange chromatography. The composition ratio of the chitosan liquid band-aid was optimized to form a film and encapsulate hUC-MSC-Exo. The biological effects of chitosan exosome liquid band-aid on human umbilical vein endothelial cells (HUVECs) were observed, and its anti-bacterial properties were tested. BALB/c mice with back skin injury were randomly divided into chitosan exosome liquid band-aid group (CS-Exo), chitosan liquid band-aid group (CS), and normal saline control group (Con), and wound healing was evaluated post-treatment. Skin tissue samples posttreatment were collected for H&E staining. RESULTS: The hUC-MSC-Exo was prepared and characterized. The optimum conditions for film formation were 1% chitosan solution and 15% poloxamer 407/poloxamer 188 (pH 5.0 ~ 7.0). The chitosan exosome liquid band-aid promoted HUVEC proliferation and migration and markedly inhibited Escherichia coli and Staphylococcus aureus growth in vitro. In vivo, the wound healing rate in the CS-Exo group was higher than that in the Con and CS groups. Fourteen days post-treatment, the wounds completely healed, and hair grew normally, which was consistent with H&E results. Mouse weights in each group did not change significantly after administration, indicating that the chitosan exosome liquid band-aid had no obvious toxic side effects. CONCLUSION: Local chitosan exosome liquid band-aid application can promote wound healing in mice, and the mechanism could be related to hUC-MSC-Exo-induced vascular endothelial cell proliferation and migration.

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Severe fever with thrombocytopenia syndrome (SFTS) is a highly fatal disease. Droplet digital polymerase chain reaction (ddPCR) presents unparalleled sensitivity and enables absolute quantification of viral load. In this prospective study, we enrolled 111 patients with SFTS and collected 259 continuous samples. Our findings unveil a robust reverse transcription (RT)-ddPCR method for SFTS with a limit of detection of 2.46 copies/µL (95% CI, 1.50-11.05), surpassing the sensitivity of RT-quantitative polymerase chain reaction at 103.29 copies/µL (95% CI, 79.69-216.35). Longitudinal cohort analysis revealed significantly higher RT-ddPCR detection rates at days 10 to 11, 13 to 14, and ≥15 of the disease course as compared with RT-quantitative polymerase chain reaction (P < .05). Positive RT-ddPCR results were associated with declined platelet and elevated aspartate aminotransferase and lactate dehydrogenase on the same day vs negative RT-ddPCR samples. RT-ddPCR exhibits commendable diagnostic efficacy in SFTS, and it remains detectable in blood samples from patients with an extended disease course. Furthermore, RT-ddPCR correlates with clinical laboratory tests, furnishing valuable reference data for clinical diagnosis.

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Objective: This study aims to examine the ultrasonographic features of secondary thyroid malignancies and compare the diagnostic efficacy of fine-needle aspiration (FNA) and core needle biopsy (CNB) in this condition. Methods: A retrospective analysis was conducted on 29 patients with secondary thyroid malignancies treated at our center between July 2011 and October 2022. Ultrasound images and clinical data were analyzed, and the lesions were classified according to the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS). Results: Among the 29 patients studied, primary tumor sites were predominantly the esophagus, lung, and nasopharynx. Comprehensive ultrasound data was available for 28 of these patients, revealing nodular lesions in 24 cases and diffuse lesions in 4 cases. Nodular lesions were predominantly solid or nearly solid hypoechoic nodules with parallel growth and extrathyroidal extension features, with a few showing macrocalcifications. Most patients had varying degrees of metastasis to neck lymph nodes. FNA accurately diagnosed 31.6 % of the lesions as secondary thyroid malignancies, while 5.3 % were misdiagnosed as papillary thyroid carcinoma (PTC). However, CNB demonstrated 100 % reliability in diagnosing secondary thyroid malignancies. Conclusion: This study's categorization of secondary thyroid malignancy ultrasonographic features identifies nodular and diffuse patterns, with the application of ACR TI-RADS proving effective for nodular types. In detecting these lesions, CNB demonstrates superior sensitivity compared to FNA. Thus, in cases of thyroid lesions suspected to be malignant, particularly with enlarged neck lymph nodes and in patients with a history of malignancy, CNB is recommended as the diagnostic method of choice.

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Objective: The aim of this study was to compare hematological parameters pre- and early post-chemotherapy, and evaluate their values for predicting febrile neutropenia (FN). Methods: Patients diagnosed with malignant solid tumors receiving chemotherapy were included. Blood cell counts peri-chemotherapy and clinical information were retrieved from the hospital information system. We used the least absolute shrinkage and selection operator (LASSO) method for variable selection and fitted selected variables to a logistic model. We assessed the performance of the prediction model by the area under the ROC curve. Results: The study population consisted of 4,130 patients with common solid tumors receiving a three-week chemotherapy regimen in Sichuan Cancer Hospital from February 2019 to March 2022. In the FN group, change percentage of neutrophil count decreased less (-0.02, CI: -0.88 to 3.48 vs. -0.04, CI: -0.83 to 2.24). Among hematological parameters, lower post-chemotherapy lymphocyte count (OR 0.942, CI: 0.934-0.949), change percentage of platelet (OR 0.965, CI: 0.955-0.975) and higher change percentage of post-chemotherapy neutrophil count (OR 1.015, CI: 1.011-1.018), and pre-chemotherapy NLR (OR 1.002, CI: 1.002-1.002) predicted an increased risk of FN. These factors improved the predicting model based on clinical factors alone. The AUC of the combination model was 0.8275. Conclusion: Peri-chemotherapy hematological markers improve the prediction of FN.

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This investigation aims to employ Olink proteomics in analyzing the distinct serum proteins associated with postmenopausal osteoporosis (PMOP) and identifying prognostic markers for early detection of PMOP via molecular mechanism research on postmenopausal osteoporosis. Postmenopausal women admitted to Beijing Jishuitan Hospital were randomly selected and categorized into three groups based on their dual-energy X-ray absorptiometry (DXA) T-scores: osteoporosis group (n = 24), osteopenia group (n = 20), and normal bone mass group (n = 16). Serum samples from all participants were collected for clinical and bone metabolism marker measurements. Olink proteomics was utilized to identify differentially expressed proteins (DEPs) that are highly associated with postmenopausal osteoporosis. The functional analysis of DEPs was performed using Gene Ontology and Kyto Encyclopedia Genes and Genomes (KEGG). The biological characteristics of these proteins and their correlation with PMOP were subsequently analyzed. ROC curve analysis was performed to identify potential biomarkers with the highest diagnostic accuracy for early stage PMOP. Through Olink proteomics, we identified five DEPs highly associated with PMOP, including two upregulated and three downregulated proteins. TWEAK and CDCP1 markers exhibited the highest area under the curve (0.8188 and 0.8031, respectively). TWEAK and CDCP1 have the potential to serve as biomarkers for early prediction of postmenopausal osteoporosis.

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BACKGROUND: To examine the associations of physical activity (PA) and sedentary behavior (SB) with longevity and age acceleration (AA) using observational and Mendelian randomization (MR) studies, and quantify the mediating effects of lipids. METHODS: In Guangzhou Biobank Cohort Study (GBCS), PA and SB were assessed by the Chinese Version of the International Physical Activity Questionnaire. Longevity was defined as participants whose age at follow-up or at death was at or above the 90th age percentile. AA was defined as the residual resulting from a linear model that regressed phenotypic age against chronological age. Linear regression and Poisson regression with robust error variance were used to assess the associations of total and specific PA in different intensities, and SB with AA and longevity, yielding ßs or relative risks (RRs) and 95% confidence intervals (CIs). Two-sample MR was conducted to examine the causal effects. Mediation analysis was used to assess the mediating effects of lipids. RESULTS: Of 20,924 participants aged 50 + years in GBCS, during an average follow-up of 15.0 years, compared with low PA, moderate and high PA were associated with higher likelihood of longevity (RR (95% CI): 1.56 (1.16, 2.11), 1.66 (1.24, 2.21), respectively), and also cross-sectionally associated with lower AA (ß (95% CI): -1.43 (-2.41, -0.45), -2.09 (-3.06, -1.11) years, respectively). Higher levels of moderate PA (MPA) were associated with higher likelihood of longevity and lower AA, whereas vigorous PA (VPA) showed opposite effects. The association of PA with longevity observed in GBCS was mediated by low-density lipoprotein cholesterol (LDL-C) by 8.23% (95% CI: 3.58-39.61%), while the association with AA was mediated through LDL-C, triglycerides and total cholesterol by 5.13% (3.94-7.30%), 7.81% (5.98-11.17%), and 3.37% (2.59-4.80%), respectively. Additionally, in two-sample MR, SB was positively associated with AA (ß (95% CI): 1.02 (0.67, 1.36) years). CONCLUSIONS: PA showed protective effects on longevity and AA, with the effects being partly mediated through lipids. Conversely, SB had a detrimental impact on AA. MPA was associated with higher likelihood of longevity and reduced AA, whereas VPA showed adverse effects. Our findings reinforce the recommendation of "sit less and move more" to promote healthy longevity, and highlight the potential risks associated with VPA in the elderly.