Dampening of ISGylation of RIG-I by ADAP regulates type I interferon response of macrophages to RNA virus infection.

While macrophage is one of the major type I interferon (IFN-I) producers in multiple tissues during viral infections, it also serves as an important target cell for many RNA viruses. However, the regulatory mechanism for the IFN-I response of macrophages to respond to a viral challenge is not fully understood. Here we report ADAP, an immune adaptor protein, is indispensable for the induction of the IFN-I response of macrophages to RNA virus infections via an inhibition of the conjugation of ubiquitin-like ISG15 (ISGylation) to RIG-I. Loss of ADAP increases RNA virus replication in macrophages, accompanied with a decrease in LPS-induced IFN-ß and ISG15 mRNA expression and an impairment in the RNA virus-induced phosphorylation of IRF3 and TBK1. Moreover, using Adap-/- mice, we show ADAP deficiency strongly increases the susceptibility of macrophages to RNA-virus infection in vivo. Mechanically, ADAP selectively interacts and functionally cooperates with RIG-I but not MDA5 in the activation of IFN-ß transcription. Loss of ADAP results in an enhancement of ISGylation of RIG-I, whereas overexpression of ADAP exhibits the opposite effect in vitro, indicating ADAP is detrimental to the RNA virus-induced ISGylation of RIG-I. Together, our data demonstrate a novel antagonistic activity of ADAP in the cell-intrinsic control of RIG-I ISGylation, which is indispensable for initiating and sustaining the IFN-I response of macrophages to RNA virus infections and replication.

WSB1/2 target chromatin-bound lysine-methylated RelA for proteasomal degradation and NF-κB termination.

Proteasome-mediated degradation of chromatin-bound NF-κB is critical in terminating the transcription of pro-inflammatory genes and can be triggered by Set9-mediated lysine methylation of the RelA subunit. However, the E3 ligase targeting methylated RelA remains unknown. Here, we find that two structurally similar substrate-recognizing components of Cullin-RING E3 ligases, WSB1 and WSB2, can recognize chromatin-bound methylated RelA for polyubiquitination and proteasomal degradation. We showed that WSB1/2 negatively regulated a subset of NF-κB target genes via associating with chromatin where they targeted methylated RelA for ubiquitination, facilitating the termination of NF-κB-dependent transcription. WSB1/2 specifically interacted with methylated lysines (K) 314 and 315 of RelA via their N-terminal WD-40 repeat (WDR) domains, thereby promoting ubiquitination of RelA. Computational modeling further revealed that a conserved aspartic acid (D) at position 158 within the WDR domain of WSB2 coordinates K314/K315 of RelA, with a higher affinity when either of the lysines is methylated. Mutation of D158 abolished WSB2's ability to bind to and promote ubiquitination of methylated RelA. Together, our study identifies a novel function and the underlying mechanism for WSB1/2 in degrading chromatin-bound methylated RelA and preventing sustained NF-κB activation, providing potential new targets for therapeutic intervention of NF-κB-mediated inflammatory diseases.

R2R3-MYB transcription factor CsMYB60 controls mature fruit skin color by regulating flavonoid accumulation in cucumber.

Skin color is an important trait that determines the cosmetic appearance and quality of fruits. In cucumber, the skin color ranges from white to brown in mature fruits. However, the genetic basis for this important trait remains unclear. We conducted a genome-wide association study of natural cucumber populations, along with map-based cloning techniques, on an F2 population resulting from a cross between Pepino (with yellow-brown fruit skin) and Zaoer-N (with creamy fruit skin). We identified CsMYB60 as a candidate gene responsible for skin coloration in mature cucumber fruits. In cucumber accessions with white to pale yellow skin color, a premature stop mutation (C to T) was found in the second exon region of CsMYB60, whereas light yellow cucumber accessions exhibited splicing premature termination caused by an intronic mutator-like element insertion in CsMYB60. Transgenic CsMYB60c cucumber plants displayed a yellow-brown skin color by promoting accumulation of flavonoids, especially hyperoside, a yellow-colored flavonol. CsMYB60c encodes a nuclear protein that primarily acts as a transcriptional activator through its C-terminal activation motif. RNA sequencing and DNA affinity purification sequencing assays revealed that CsMYB60c promotes skin coloration by directly binding to the YYTACCTAMYT motif in the promoter regions of flavonoid biosynthetic genes, including CsF3'H, which encodes flavonoid 3'-hydroxylase. The findings of our study not only offer insight into the function of CsMYB60 as dominantly controlling fruit coloration, but also highlight that intronic DNA mutations can have a similar phenotypic impact as exonic mutations, which may be valuable in future cucumber breeding programs.

Reviving resilience: MEcPP-mediated ASK1-IMPα-9-TRP2 stress-responsive module.

Chloroplasts are not only critical photosynthesis sites in plants, but they also participate in plastidial retrograde signaling in response to developmental and environmental signals. MEcPP (2-C-Methyl-D-erythritol-2,4-cyclopyrophosphate) is an intermediary in the methylerythritol phosphate (MEP) pathway in chloroplasts. It is a critical precursor for the synthesis of isoprenoids and terpenoid derivatives, which play crucial roles in plant growth and development, photosynthesis, reproduction, and defense against environmental constraints. Accumulation of MEcPP under stressful conditions triggers the expression of IMPα-9 and TPR2, contributing to the activation of abiotic stress-responsive genes. In this correspondence, we discuss plastidial retrograde signaling in support of a recently published paper in Molecular Plant (Zeng et al. 2024). We hope that it can shed more insight on the retrograde signaling cascade.

MOTAI: A Novel Method for the Study of O-GalNAcylation and Complex O-Glycosylation in Cancer.

The Tn antigen, an immature truncated O-glycosylation, is a promising biomarker for cancer detection and diagnosis. However, reliable methods for analyzing O-GalNAcylation and complex O-glycosylation are lacking. Here, we develop a novel method, MOTAI, for the sequential analysis of O-glycosylation using different O-glycoproteases. MOTAI conjugates glycopeptides on a solid support and releases different types of O-glycosylation through sequential enzymatic digestion by O-glycoproteases, including OpeRATOR and IMPa. Because OpeRATOR has less activity on O-GalNAcylation, MOTAI enriches O-GalNAcylation for subsequent analysis. We demonstrate the effectiveness of MOTAI by analyzing fetuin O-glycosylation and Jurkat cell lines. We then apply MOTAI to analyze colorectal cancer and benign colorectal polyps. We identify 32 Tn/sTn-glycoproteins and 43 T/sT-glycoproteins that are significantly increased in tumor tissues. Gene Ontology analysis reveals that most of these proteins are ECM proteins involved in the adhesion process of the intercellular matrix. Additionally, the protein disulfide isomerase CRELD2 has a significant difference in Tn expression, and the abnormally glycosylated T345 and S349 O-glycosylation sites in cancer group samples may promote the secretion of CRELD2 and ultimately tumorigenesis through ECM reshaping. In summary, MOTAI provides a powerful new tool for the in-depth analysis of O-GalNAcylation and complex O-glycosylation. It also reveals the upregulation of Tn/sTn-glycoproteins in colorectal cancer, which may provide new insights into cancer biology and biomarker discovery.

Insight into Anionic Discrepancies in Bipolar Poly(Thionine) Organic Cathodes for Aqueous Zinc Ion Batteries.

Electroactive organic electrode materials exhibit remarkable potential in aqueous zinc ion batteries (AZIBs) due to their abundant availability, customizable structures, sustainability, and high reversibility. However, the research on AZIBs has predominantly concentrated on unraveling the storage mechanism of zinc cations, often neglecting the significance of anions in this regard. Herein, bipolar poly(thionine) is synthesized by a simple and efficient polymerization reaction, and the kinetics of different anions are investigated using poly(thionine) as the cathode of AZIBs. Notably, poly(thionine) is a bipolar organic polymer electrode material and exhibits enhanced stability in aqueous solutions compared to thionine monomers. Kinetic analysis reveals that ClO4 - exhibits the fastest kinetics among SO4 2-, Cl-, and OTF-, demonstrating excellent rate performance (109 mAh g-1 @ 0.5 A g-1 and 92 mAh g-1 @ 20 A g-1). Mechanism studies reveal that the poly(thionine) cathode facilitates the co-storage of both anions and cations in Zn(ClO4)2. Furthermore, the lower electrostatic potential of ClO4 - influences the strength of hydrogen bonding with water molecules, thereby enhancing the overall kinetics in aqueous electrolytes. This work provides an effective strategy for synthesizing high-quality organic materials and offers new insights into the kinetic behavior of anions in AZIBs.

Editing of ORF138 restores fertility of Ogura cytoplasmic male sterile broccoli via mitoTALENs.

Cytoplasmic male sterility (CMS), encoded by the mitochondrial open reading frames (ORFs), has long been used to economically produce crop hybrids. However, the utilization of CMS also hinders the exploitation of sterility and fertility variation in the absence of a restorer line, which in turn narrows the genetic background and reduces biodiversity. Here, we used a mitochondrial targeted transcription activator-like effector nuclease (mitoTALENs) to knock out ORF138 from the Ogura CMS broccoli hybrid. The knockout was confirmed by the amplification and re-sequencing read mapping to the mitochondrial genome. As a result, knockout of ORF138 restored the fertility of the CMS hybrid, and simultaneously manifested a cold-sensitive male sterility. ORF138 depletion is stably inherited to the next generation, allowing for direct use in the breeding process. In addition, we proposed a highly reliable and cost-effective toolkit to accelerate the life cycle of fertile lines from CMS-derived broccoli hybrids. By applying the k-mean clustering and interaction network analysis, we identified the central gene networks involved in the fertility restoration and cold-sensitive male sterility. Our study enables mitochondrial genome editing via mitoTALENs in Brassicaceae vegetable crops and provides evidence that the sex production machinery and its temperature-responsive ability are regulated by the mitochondria.

Phenotypic plasticity for improved light harvesting, in tandem with methylome repatterning in reef-building corals.

Acclimatization through phenotypic plasticity represents a more rapid response to environmental change than adaptation and is vital to optimize organisms' performance in different conditions. Generally, animals are less phenotypically plastic than plants, but reef-building corals exhibit plant-like properties. They are light dependent with a sessile and modular construction that facilitates rapid morphological changes within their lifetime. We induced phenotypic changes by altering light exposure in a reciprocal transplant experiment and found that coral plasticity is a colony trait emerging from comprehensive morphological and physiological changes within the colony. Plasticity in skeletal features optimized coral light harvesting and utilization and paralleled significant methylome and transcriptome modifications. Network-associated responses resulted in the identification of hub genes and clusters associated to the change in phenotype: inter-partner recognition and phagocytosis, soft tissue growth and biomineralization. Furthermore, we identified hub genes putatively involved in animal photoreception-phototransduction. These findings fundamentally advance our understanding of how reef-building corals repattern the methylome and adjust a phenotype, revealing an important role of light sensing by the coral animal to optimize photosynthetic performance of the symbionts.

Upconversion photoluminescence of monolayer WSe2 with biaxial strain tuning.

Mechanical strain can be used to tune the optical properties of monolayer transition metal dichalcogenides (1L-TMDs). Here, upconversion photoluminescence (UPL) from 1L-WSe2 flakes is tuned with biaxial strain induced by cruciform bending and indentation method. It is found that the peak position of UPL is redshifted by around 24 nm as the applied biaxial strain increases from 0% to 0.51%. At the same time, the UPL intensity increases exponentially for the upconversion energy difference that lies within a broad range between -157 meV to -37 meV. The observed linear and sublinear power dependence of UPL emission in 1L-WSe2 with and without biaxial strain at three different excitation wavelengths of 784 nm, 800 nm, and 820 nm indicates the multiphonon-assisted one-photon upconversion emission process. The results of strain-dependent UPL emission from 1L-TMDs pave a unique path to the advances in photon upconversion applications and optoelectronic devices.

Infrared phase-change chiral metasurfaces with tunable circular dichroism.

Integrating phase-change materials in metasurfaces has emerged as a powerful strategy to realize optical devices with tunable electromagnetic responses. Here, phase-change chiral metasurfaces based on GST-225 material with the designed trapezoid-shaped resonators are demonstrated to achieve tunable circular dichroism (CD) responses in the infrared regime. The asymmetric trapezoid-shaped resonators are designed to support two chiral plasmonic resonances with opposite CD responses for realizing switchable CD between negative and positive values using the GST phase change from amorphous to crystalline. The electromagnetic field distributions of the chiral plasmonic resonant modes are analyzed to understand the chiroptical responses of the metasurface. Furthermore, the variations in the absorption spectrum and CD value for the metasurface as a function of the baking time during the GST phase transition are analyzed to reveal the underlying thermal tuning process of the metasurface. The demonstrated phase-change metasurfaces with tunable CD responses hold significant promise in enabling many applications in the infrared regime such as chiral sensing, encrypted communication, and thermal imaging.

Root topological order drives variation of fine root vessel traits and hydraulic strategies in tropical trees.

Vessel traits contribute to plant water transport from roots to leaves and thereby influence how plants respond to soil water availability, but the sources of variation in fine root anatomical traits remain poorly understood. Here, we explore the variations of fine root vessel traits along topological orders within and across tropical tree species. Anatomical traits were measured along five root topological orders in 80 individual trees of 20 species from a tropical forest in southwestern China. We found large variations for most root anatomical traits across topological orders, and strong co-variations between vessel traits. Within species, theoretical specific xylem hydraulic conductivity (Kth) increased with topological order due to increased mean vessel diameter, size heterogeneity, and decreased vessel density. Across species, Kth was associated with vessel fraction in low-order roots and correlated with mean vessel diameter and vessel density in high-order roots, suggesting a shift in relative anatomical contributors to Kth from the second- to fifth-order roots. We found no clear relationship between Kth and stele: root diameter ratios. Our study shows strong variations in root vessel traits across topological orders and species, and highlights shifts in the anatomical underpinnings by varying vessel-related anatomical structures for an optimized water supply.

Shift in the rhizosphere soil fungal community associated with root rot infection of Plukenetia volubilis Linneo caused by Fusarium and Rhizopus species.

BACKGROUND: Plukenetia volubilis Linneo is an oleaginous plant belonging to the family Euphorbiaceae. Due to its seeds containing a high content of edible oil and rich in vitamins, P. volubilis is cultivated as an economical plant worldwide. However, the cultivation and growth of P. volubilis is challenged by phytopathogen invasion leading to production loss. METHODS: In the current study, we tested the pathogenicity of fungal pathogens isolated from root rot infected P. volubilis plant tissues by inoculating them into healthy P. volubilis seedlings. Metagenomic sequencing was used to assess the shift in the fungal community of P. volubilis rhizosphere soil after root rot infection. RESULTS: Four Fusarium isolates and two Rhizopus isolates were found to be root rot causative agents of P. volubilis as they induced typical root rot symptoms in healthy seedlings. The metagenomic sequencing data showed that root rot infection altered the rhizosphere fungal community. In root rot infected soil, the richness and diversity indices increased or decreased depending on pathogens. The four most abundant phyla across all samples were Ascomycota, Glomeromycota, Basidiomycota, and Mortierellomycota. In infected soil, the relative abundance of each phylum increased or decreased depending on the pathogen and functional taxonomic classification. CONCLUSIONS: Based on our results, we concluded that Fusarium and Rhizopus species cause root rot infection of P. volubilis. In root rot infected P. volubilis, the shift in the rhizosphere fungal community was pathogen-dependent. These findings may serve as a key point for a future study on the biocontrol of root rot of P. volubilis.

Recycling Organic Dyes within the Metal-Organic Framework for Photothermal Conversion.

The pursuit of a straightforward method to recycle organic dyes from effluents and repurpose them into valuable materials represents a highly sought-after yet huge challenge within the realms of chemistry, environment, and materials science. In this context, we employ a host-guest strategy that leverages the recycling of the rhodamine B molecule within the porous structure of a metal-organic framework to facilitate photothermal conversion. This achievement is realized through the electrostatic interaction, which then gives rise to remarkable selectivity and unparalleled uptake capacity for the cationic rhodamine B molecule. Capitalizing on this approach, the application of a columnar device and membrane technology for efficiently trapping rhodamine B molecules becomes feasible. On account of the aggregation effect resulting from the confined pore structure of the host matrix, the fluorescence emission of the encapsulated RhB molecules is significantly reduced, which consequently enhances the photothermal performance of the hybrid material through nonradiative transition. Moreover, the photothermal conversion achieved showcases a myriad of high-performance applications, including bacterial inhibition against Escherichia coli and seawater desalination.

Quantification and Characterization of Fine Plastic Particles as Considerable Components in Atmospheric Fine Particles.

The negative effects of air pollution, especially fine particulate matter (PM2.5, particles with an aerodynamic diameter of ≤2.5 µm), on human health, climate, and ecosystems are causing significant concern. Nevertheless, little is known about the contributions of emerging pollutants such as plastic particles to PM2.5 due to the lack of continuous measurements and characterization methods for atmospheric plastic particles. Here, we investigated the levels of fine plastic particles (FPPs) in PM2.5 collected in urban Shanghai at a 2 h resolution by using a novel versatile aerosol concentration enrichment system that concentrates ambient aerosols up to 10-fold. The FPPs were analyzed offline using the combination of spectroscopic and microscopic techniques that distinguished FPPs from other carbon-containing particles. The average FPP concentrations of 5.6 µg/m3 were observed, and the ratio of FPPs to PM2.5 was 13.2% in this study. The FPP sources were closely related to anthropogenic activities, which pose a potential threat to ecosystems and human health. Given the dramatic increase in plastic production over the past 70 years, this study calls for better quantification and control of FPP pollution in the atmosphere.

High Strength UV-Resistant Composite Film of Fe3+-Coordination Lignin/PVA.

The literature on polyvinyl alcohol (PVA) films is extensive, however, these methods often necessitate intricate synthesis processes or the addition of plasticizers to modify the strength and water solubility of the PVA material. A high-strength UV radiation-resistant composite film by chelating Fe3+ with lignin and PVA, which exhibits excellent hydrolysis resistance is developed. This composite film is prepared simply by incorporating a small amount of dealkalized lignin (APPL) and ferric chloride (FeCl3) into PVA through a straightforward composite process. During the scanning test, it is noted that the film exhibits a high density of uniformly dispersed particles, endowing it with efficient ultraviolet absorption capabilities. The infrared and anti-dissolution tests reveal that the coordination of Fe3+ with lignin imparts an outstanding hydrolysis resistance to the film, obviating the need for any extender, curing agent, acid or base. The tensile fracture strength reaches an impressive 187.81Mpa in the tensile test. UV and indicator card tests unequivocally demonstrate that the film achieves a remarkable 100% anti-UV efficiency. This Fe3+ chelated lignin/PVA composite film, with its facile preparation, environmental sustainability, high strength, and outstanding anti-ultraviolet efficiency, can be deployed across diverse applications requiring robust protection against ultraviolet radiation.

Transition from Schottky to Ohmic contacts in 2D Ge/GaAs heterostructures with high tunneling probability.

The metal-semiconductor (M-S) contact is usually an Ohmic contact or a Schottky contact, which greatly affects the electronic properties of devices, and it remains a huge challenge to realize a low-resistance Ohmic contact in a metal-semiconductor junction (MSJ). Herein, we systematically studied the band structures, electrostatic potential, charge transfer, Schottky barrier height of carriers, effective carrier masses, and tunneling probability of carriers of a germanene (Ge)/GaAs MSJ. The transition from the Schottky to the Ohmic contact can be caused by applying certain biaxial strains or electric fields, which weakens the Fermi level pinning (FLP) effect and reduces contact resistance. Meanwhile, the electron injection efficiency of Ge/(GaAs)As MSJ (PTB > 27%) is far superior to that of other two-dimensional (2D) vdW MSJs. This work indicates that Ge/GaAs heterostructures are the most compatible for applying high-effective 2D electronic nanodevices under controllable conditions.

Conformal thyroidectomy is a feasible option in papillary thyroid microcarcinoma: a retrospective cohort study with 10-year follow-up results.

BACKGROUND: In recent years, there has been an increasing prevalence of patients with papillary thyroid microcarcinoma (PTMC) without lymph node involvement in medical centers worldwide. For patients who are unable to undergo active surveillance (AS) and are afraid of postoperative complications, conformal thyroidectomy may be a suitable option to ensure both preservation of function and complete removal of the tumor. METHODS: The patients in the cohort during 2010 to 2015 were retrospectively enrolled strictly following the inclusion and exclusion criteria. The observation and control groups were defined based on the surgical approach, with patients in the observation group undergoing conformal thyroidectomy and patients in the control group undergoing lobectomy. Event-free survival (EFS), the interval from initial surgery to the detection of recurrent or metastatic disease, was defined as the primary observation endpoint. RESULTS: A total of 319 patients were included in the study, with 124 patients undergoing conformal thyroidectomy and 195 patients undergoing lobectomy. When compared to lobectomy, conformal thyroidectomy demonstrated reduced hospital stays, shorter operative times, and lower rates of vocal cord paralysis and hypoparathyroidism. Furthermore, the mean bleeding volume during the operation and the rate of permanent hypothyroidism were also lower in the conformal thyroidectomy group than in the lobectomy group. However, there was no statistically significant difference observed in the 5- and 10-year EFS between the two groups. CONCLUSIONS: Conformal thyroidectomy had advantages in perioperative management and short-term complication rates, with an EFS that was not inferior to that of lobectomy. Thus, conformal thyroidectomy is a feasible option for low-risk PTMC patients.

Guideline for the diagnosis and treatment of incomplete Kawasaki disease in children in China.

BACKGROUND: Kawasaki disease (KD) is a pyretic ailment predominantly observed in children aged below 5 years. There is currently a dearth of precise markers for timely identification of incomplete Kawasaki disease (IKD). It is imperative to develop updated, comprehensive, and evidence-based guidelines to effectively direct clinical practice. METHODS: The guideline development group comprised individuals with diverse expertise in both content and methodology and carried out an extensive exploration of the following digital repositories: CNKI, VIP, Wanfang Data, UpToDate, BMJ, Clinical Evidence, National Guideline Clearinghouse, Joanna Briggs Institute Library, Cochrane Library, and PubMed. The entire period from the establishment of these databases until January 1, 2024 was covered. To evaluate IKD, systematic reviews and randomised controlled trials were assessed using the risk of prejudice instrument specified in the Cochrane Handbook, along with the evidence robustness framework established by the GRADE group. The recommendations were formulated based on the findings, considering the evidence strength. After several iterations of expert consensus, the relevant professional committees in China endorsed the ultimate guideline. RESULTS: These guidelines address clinical questions regarding the classification and definition of KD, diagnosis of IKD, treatment during the acute phase of IKD, and follow-up of IKD. CONCLUSIONS: To provide healthcare professionals with guidance and decision-making bases for the diagnosis and treatment of IKD in China, 13 recommendations were formulated based on expert consensus and evidence of best practices.

Knockdown of the UL-16 binding protein 1 promotes osteoblast differentiation of human mesenchymal stem cells by activating the SMAD2/3 pathway.

Osteoporosis is caused by the imbalance of osteoblasts and osteoclasts. The regulatory mechanisms of differentially expressed genes (DEGs) in pathogenesis of osteoporosis are of significant and needed to be further investigated. GSE100609 dataset downloaded from Gene Expression Omnibus (GEO) database was used to identified DEGs in osteoporosis patients. KEGG analysis was conducted to demonstrate signaling pathways related to enriched genes. Osteoporosis patients and the human mesenchymal stem cells (hMSCs) were obtained for in vivo and in vitro resaerch. Lentivirus construction and viral infection was used to knockdown genes. mRNA expression and protein expression were detected via qRT-PCR and western blot assay separately. Alkaline phosphatase (ALP) activity detection, alizarin Red S (ARS) staining, and expression of bone morphogenetic protein 2 (BMP2), osteocalcin (OCN) and Osterix were evaluated to determine osteoblast differentiation capacity. UL-16 binding protein 1 (ULBP1) gene was upregulated in osteoporosis and downregulated in differentiated hMSCs. Knockdown of ULBP1 increased ALP activity, mineralization ability evaluated by ARS staining, expression of BMP2, OCN and Osterix in differentiated hMSCs. Furthermore, rescue experiment demonstrated that suppressed ULBP1 boosted osteoblast differentiation by activating TNF-ß signaling pathway. Knockdown of ULBP1 gene could promoted osteoblast differentiation by activating TNF-ß signaling pathway in differentiated hMSCs. ULBP1 may be a the Achilles' heel of osteoporosis, and suppression of ULBP1 could be a promising treatment for osteoporosis.

"I Will Exercise to Look Great!": The Impact of Message Frame, Message Focus, and Age Label on Enhancing Older Adults' Physical Activity Intentions.

Promoting physical activity (PA) in older adults is a long-standing and crucial aspect of public health. It is essential for improving quality of life and maintaining overall health as people age. This study aims to identify an effective message strategy for enhancing PA intentions in aging population. Using a between subjects, 2 [message frame: gain versus loss] × 2 [message focus: health versus appearance] × 2 [age label: presence versus absence] full factorial survey experiment, this study uncovered a significant main effect for message framing. Gain-framed messages elicited more positive PA attitudes than loss-framed messages among older adults, and this effect of message frame further varied upon different message focuses and age label conditions. Moreover, moderated mediation analyses showed that gain-framed messages exerted a stronger indirect effect on PA intentions through PA attitudes when older adults received appearance-focused messages with age labels than without. The theoretical and practical implications of tailoring health promotion messages targeting older adults were discussed.