Immune aging - A mechanism in autoimmune disease.

Evidence is emerging that the process of immune aging is a mechanism leading to autoimmunity. Over lifetime, the immune system adapts to profound changes in hematopoiesis and lymphogenesis, and progressively restructures in face of an ever-expanding exposome. Older adults fail to generate adequate immune responses against microbial infections and tumors, but accumulate aged T cells, B cells and myeloid cells. Age-associated B cells are highly efficient in autoantibody production. T-cell aging promotes the accrual of end-differentiated effector T cells with potent cytotoxic and pro-inflammatory abilities and myeloid cell aging supports a low grade, sterile and chronic inflammatory state (inflammaging). In pre-disposed individuals, immune aging can lead to frank autoimmune disease, manifesting with chronic inflammation and irreversible tissue damage. Emerging data support the concept that autoimmunity results from aging-induced failure of fundamental cellular processes in immune effector cells: genomic instability, loss of mitochondrial fitness, failing proteostasis, dwindling lysosomal degradation and inefficient autophagy. Here, we have reviewed the evidence that malfunctional mitochondria, disabled lysosomes and stressed endoplasmic reticula induce pathogenic T cells and macrophages that drive two autoimmune diseases, rheumatoid arthritis (RA) and giant cell arteritis (GCA). Recognizing immune aging as a risk factor for autoimmunity will open new avenues of immunomodulatory therapy, including the repair of malfunctioning mitochondria and lysosomes.

A review: analysis of technical challenges in cultured meat production and its commercialization.

The cultured meat technology has developed rapidly in recent years, but there are still many technical challenges that hinder the large-scale production and commercialization of cultured meat. Firstly, it is necessary to lay the foundation for cultured meat production by obtaining seed cells and maintaining stable cell functions. Next, technologies such as bioreactors are used to expand the scale of cell culture, and three-dimensional culture technologies such as scaffold culture or 3D printing are used to construct the three-dimensional structure of cultured meat. At the same time, it can reduce production costs by developing serum-free medium suitable for cultured meat. Finally, the edible quality of cultured meat is improved by evaluating food safety and sensory flavor, and combining ethical and consumer acceptability issues. Therefore, this review fully demonstrates the current development status and existing technical challenges of the cultured meat production technology with regard to the key points described above, in order to provide research ideas for the industrial production of cultured meat.

Structural basis for GTP-induced dimerization and antiviral function of guanylate-binding proteins.

Guanylate-binding proteins (GBPs) form a family of dynamin-related large GTPases which mediate important innate immune functions. They were proposed to form oligomers upon GTP binding/hydrolysis, but the molecular mechanisms remain elusive. Here, we present crystal structures of C-terminally truncated human GBP5 (hGBP51-486), comprising the large GTPase (LG) and middle (MD) domains, in both its nucleotide-free monomeric and nucleotide-bound dimeric states, together with nucleotide-free full-length human GBP2. Upon GTP-loading, hGBP51-486 forms a closed face-to-face dimer. The MD of hGBP5 undergoes a drastic movement relative to its LG domain and forms extensive interactions with the LG domain and MD of the pairing molecule. Disrupting the MD interface (for hGBP5) or mutating the hinge region (for hGBP2/5) impairs their ability to inhibit HIV-1. Our results point to a GTP-induced dimerization mode that is likely conserved among all GBP members and provide insights into the molecular determinants of their antiviral function.

Feature shared multi-decoder network using complementary learning for Photon counting CT ring artifact suppression.

BACKGROUND: Photon-counting computed tomography (Photon counting CT) utilizes photon-counting detectors to precisely count incident photons and measure their energy. These detectors, compared to traditional energy integration detectors, provide better image contrast and material differentiation. However, Photon counting CT tends to show more noticeable ring artifacts due to limited photon counts and detector response variations, unlike conventional spiral CT. OBJECTIVE: To comprehensively address this issue, we propose a novel feature shared multi-decoder network (FSMDN) that utilizes complementary learning to suppress ring artifacts in Photon counting CT images. METHODS: Specifically, we employ a feature-sharing encoder to extract context and ring artifact features, facilitating effective feature sharing. These shared features are also independently processed by separate decoders dedicated to the context and ring artifact channels, working in parallel. Through complementary learning, this approach achieves superior performance in terms of artifact suppression while preserving tissue details. RESULTS: We conducted numerous experiments on Photon counting CT images with three-intensity ring artifacts. Both qualitative and quantitative results demonstrate that our network model performs exceptionally well in correcting ring artifacts at different levels while exhibiting superior stability and robustness compared to the comparison methods. CONCLUSIONS: In this paper, we have introduced a novel deep learning network designed to mitigate ring artifacts in Photon counting CT images. The results illustrate the viability and efficacy of our proposed network model as a new deep learning-based method for suppressing ring artifacts.

The thymus regulates skeletal muscle regeneration by directly promoting satellite cell expansion.

The thymus is the central immune organ, but it is known to progressively degenerate with age. As thymus degeneration is paralleled by the wasting of aging skeletal muscle, we speculated that the thymus may play a role in muscle wasting. Here, using thymectomized mice, we show that the thymus is necessary for skeletal muscle regeneration, a process tightly associated with muscle aging. Compared to control mice, the thymectomized mice displayed comparable growth of muscle mass, but decreased muscle regeneration in response to injury, as evidenced by small and sparse regenerative myofibers along with inhibited expression of regeneration-associated genes myh3, myod, and myogenin. Using paired box 7 (Pax7)-immunofluorescence staining and 5-Bromo-2'-deoxyuridine-incorporation assay, we determined that the decreased regeneration capacity was caused by a limited satellite cell pool. Interestingly, the conditioned culture medium of isolated thymocytes had a potent capacity to directly stimulate satellite cell expansion in vitro. These expanded cells were enriched in subpopulations of quiescent satellite cells (Pax7highMyoDlowEdUpos) and activated satellite cells (Pax7highMyoDhighEdUpos), which were efficiently incorporated into the regenerative myofibers. We thus propose that the thymus plays an essential role in muscle regeneration by directly promoting satellite cell expansion and may function profoundly in the muscle aging process.

DNA and coding/non-coding RNA methylation analysis provide insights into tomato fruit ripening.

Ripening is the last, irreversible developmental stage during which fruit become palatable, thus promoting seed dispersal by frugivory. In Alisa Craig fruit, mRNAs with increasing m5C levels, such as STPK and WRKY 40, were identified as being involved in response to biotic and abiotic stresses. Furthermore, two mRNAs involved in cell wall metabolism, PG and EXP-B1, also presented increased m5C levels. In the Nr mutant, several m5C-modified mRNAs involved in fruit ripening, including those encoding WRKY and MADS-box proteins, were found. Targets of long non-coding RNAs and circular RNAs with different m5C sites were also found; these targets included 2-alkenal reductase, soluble starch synthase 1, WRKY, MADS-box, and F-box/ketch-repeat protein SKIP11. A combined analysis of changes in 5mC methylation and mRNA revealed many differentially expressed genes with differentially methylated regions encoding transcription factors and key enzymes related to ethylene biosynthesis and signal transduction; these included ERF084, EIN3, AP2/ERF, ACO5, ACS7, EIN3/4, EBF1, MADS-box, AP2/ERF, and ETR1. Taken together, our findings contribute to the global understanding of the mechanisms underlying fruit ripening, thereby providing new information for both fruit and post-harvest behavior.

Emerging Roles of FHY3 and FAR1 as System Integrators in Plant Development.

FAR-RED ELONGATED HYPOCOTYL3 (FHY3) and its homolog FAR-RED-IMPAIRED RESPONSE1 (FAR1) are transcription factors derived from transposases essential for phytochrome A-mediated light signaling. In addition to their essential role in light signaling, FHY3 and FAR1 also play diverse regulatory roles in plant growth and development, including clock entrainment, seed dormancy and germination, senescence, chloroplast formation, branching, flowering and meristem development. Notably, accumulating evidence indicates that the emerging role of FHY3 and FAR1 in environmental stress signaling has begun to be revealed. In this review, we summarize these recent findings in the context of FHY3 and FAR1 as integrators of light and other developmental and stressful signals. We also discuss the antagonistic action of FHY3/FAR1 and Phytochrome Interating Factors (PIFs) in various cross-talks between light, hormone and environmental cues.

T cell aging as a risk factor for autoimmunity.

Immune aging is a complex process rendering the host susceptible to cancer, infection, and insufficient tissue repair. Many autoimmune diseases preferentially occur during the second half of life, counterintuitive to the concept of excess adaptive immunity driving immune-mediated tissue damage. T cells are particularly susceptible to aging-imposed changes, as they are under extreme proliferative pressure to fulfill the demands of clonal expansion and of homeostatic T cell repopulation. T cells in older adults have a footprint of genetic and epigenetic changes, lack mitochondrial fitness, and fail to maintain proteostasis, diverging them from host protection to host injury. Here, we review recent progress in understanding how the human T-cell system ages and the evidence detailing how T cell aging contributes to autoimmune conditions. T cell aging is now recognized as a risk determinant in two prototypic autoimmune syndromes; rheumatoid arthritis and giant cell arteritis. The emerging concept adds susceptibility to autoimmune and autoinflammatory disease to the spectrum of aging-imposed adaptations and opens new opportunities for immunomodulatory therapy by restoring the functional intactness of aging T cells.

Angular Power Spectrum of Gravitational-Wave Transient Sources as a Probe of the Large-Scale Structure.

We present a new, simulation-based inference method to compute the angular power spectrum of the distribution of foreground gravitational-wave transient events. As a first application of this method, we use the binary black hole mergers observed during the LIGO, Virgo, and KAGRA third observation run to test the spatial distribution of these sources. We find no evidence for anisotropy in their angular distribution. We discuss further applications of this method to investigate other gravitational-wave source populations and their correlations to the cosmological large-scale structure.

A unique mutation in PIN-FORMED1 and a genetic pathway for reduced sensitivity of Arabidopsis roots to N-1-naphthylphthalamic acid.

The small chemical N-1-naphthylphthalamic acid (NPA) has long been used as a polar auxin transport inhibitor. Recent biochemical and structural investigations have revealed that this molecule competes with the auxin IAA (indole-3-acetic acid) inside the PIN-FORMED auxin efflux carriers. However, the existence of any mutations in PIN family proteins capable of uncoupling the docking of IAA from NPA remains unclear. We report that Arabidopsis thaliana seedlings overexpressing SMALL AUXIN UP RNA 41 were hypersensitive to NPA-induced root elongation inhibition. We mutagenized this line to improve the genetic screening efficiency for NPA hyposensitivity mutants. Using bulked segregation analysis and mapping-by-sequencing assessment of these mutants, we identified a core genetic pathway for NPA-induced root elongation inhibition, including genes required for auxin biosynthesis, transportation, and signaling. To evaluate specific changes of auxin signaling activity in mutant roots before and after NPA treatment, the DR5::GFP/DR5::YFP markers were introduced and observed. Most importantly, we discovered a unique mutation in the PIN1 protein, substituting a proline residue with leucine at position 584, leading to a loss of NPA sensitivity while keeping the auxin efflux capacity. Transforming the null mutant pin1-201 with the PIN1::PIN1P584L -GFP fusion construct rescued the PIN1 function and provided NPA hyposensitivity. The proline residue is predicted to be adjacent to a hinge in the middle region of the ninth transmembrane helix of PIN1 and is conserved from moss to higher plants. Our work may bring new insights into the engineering of NPA-resistant PINs for auxin biology studies.

Identification, characterization and chemical management of Alternaria alternata causing blackcurrant leaf spot in China.

AIM: The aims of this study were to identify the pathogen causing blackcurrant leaf spot, assess the pathogenicity of different isolates, the host range, and the sensitivity to common fungicides, and test the effectiveness of field control for controlling A. alternata in blackcurrants in China, and potentially elsewhere. METHODS AND RESULTS: In 2020 and 2021, an uncommon leaf spot on blackcurrants was observed in Harbin (125°42'-130°10'E, 44°04'-46°40'N), Heilongjiang Province, China. Based on morphological, molecular characteristics, and phylogenetic analyses, 10 fungal isolates, identified as Alternaria alternata, were obtained from infected blackcurrant leaves of 10 infected plants in this study. To our knowledge, this is the first description of A. alternata as a causal agent of leaf spot on blackcurrants in China. A. alternata has a wide host range and infects eight of the 10 crop and ornamental plants evaluated, namely Sorbus pohuashanensis, Malus pumila, Rosa davurica, Padus racemosa, Hippophae rhamnoides, Crataegus pinnatifida, Pyrus ussuriensis, and Sambucus williamsii, but not Viburnum trilobum and Prunus tomentosa. Moreover, ten blackcurrant cultivars were screened and found to have contrasting levels of resistance to A. alternata. One was moderately resistant, four were resistant, four were susceptible, and one was highly susceptible. The A. alternata isolate was most sensitive to propiconazole-azoxystrobin, with EC50 values of 0.0038 µg ml-1 and efficacy ranging between 83.34% and 84.13% at 317 µg ml-1 in the field. CONCLUSIONS: The work reported that A. alternata is the pathogen that causes blackcurrant leaf spot in northern China. It can infect a variety of crops and ornamental plants. Considering the control cost and effect, propiconazole-azoxystrobin is more suitable for controlling leaf spot in the field.

Zika virus elicits inflammation to evade antiviral response by cleaving cGAS via NS1-caspase-1 axis.

Viral infection triggers host innate immune responses, which primarily include the activation of type I interferon (IFN) signaling and inflammasomes. Here, we report that Zika virus (ZIKV) infection triggers NLRP3 inflammasome activation, which is further enhanced by viral non-structural protein NS1 to benefit its replication. NS1 recruits the host deubiquitinase USP8 to cleave K11-linked poly-ubiquitin chains from caspase-1 at Lys134, thus inhibiting the proteasomal degradation of caspase-1. The enhanced stabilization of caspase-1 by NS1 promotes the cleavage of cGAS, which recognizes mitochondrial DNA release and initiates type I IFN signaling during ZIKV infection. NLRP3 deficiency increases type I IFN production and strengthens host resistance to ZIKVin vitro and in vivo Taken together, our work unravels a novel antagonistic mechanism employed by ZIKV to suppress host immune response by manipulating the interplay between inflammasome and type I IFN signaling, which might guide the rational design of therapeutics in the future.

Adenovirus vaccine therapy with CD137L promotes CD8+ DCs-mediated multifunctional CD8+ T cell immunity and elicits potent anti-tumor activity.

Renal carcinoma progresses aggressively in patients with metastatic disease while curative strategies are limited. Here, we constructed a recombinant non-replicating adenovirus (Ad) vaccine encoding an immune activator, CD137L, and a tumor antigen, CAIX, for treating renal carcinoma. In a subcutaneous tumor model, tumor growth was significantly suppressed in the Ad-CD137L/CAIX vaccine group compared with the single vaccine group. The induction and maturity of CD11C+ and CD8+CD11C+ dendritic cell (DC) subsets were promoted in Ad-CD137L/CAIX co-immunized mice. Furthermore, the Ad-CD137L/CAIX vaccine elicited stronger tumor-specific multifunctional CD8+ T cell immune responses as demonstrated by increased proliferation and cytolytic function of CD8+ T cells. Notably, depletion of CD8+ T cells greatly compromised the effective protection provided by Ad-CD137L/CAIX vaccine, suggesting an irreplaceable role of CD8+ T cells for the immunopotency of the vaccine. In both lung metastatic and orthotopic models, Ad-CD137L/CAIX vaccine treatment significantly decreased tumor metastasis and progression and increased the induction of tumor-specific multifunctional CD8+ T cells, in contrast to treatment with the Ad-CAIX vaccine alone. The Ad-CD137L/CAIX vaccine also augmented the tumor-specific multifunctional CD8+ T cell immune response in both orthotopic and metastatic models. These results indicated that Ad-CD137L/CAIX vaccine elicited a potent anti-tumor activity by inducing CD8+DC-mediated multifunctional CD8+ T cell immune responses. The potential strategy of CD137L-based vaccine might be served as a novel treatment for renal carcinoma or other malignant tumors.

Sex-specific neurobehavioural outcomes and brain stimulation pattern in adult offspring paternally exposed to methamphetamine.

Paternal methamphetamine (METH) exposure results in long-term behavioural deficits in the sub-generations with a sex difference. Here, we aim to investigate the sex-specific neurobehavioural outcomes in the first-generation offspring mice (F1 mice) paternally exposed to METH prior to conception and explore the underlying brain mechanisms. We found that paternal METH exposure increased anxiety-like behaviours and spatial memory deficits only in female F1 mice and caused depression-like behaviours in the offspring without sex-specific differences. In parallel, METH-sired F1 mice exhibited sex-specific brain activity pattern in response to mild stimulus (in water at room temperature for 3 min). Overall, paternal METH exposure caused a blunting phenomenon of prelimbic cortex (PrL), infralimbic cortex (IL) and nucleus accumbens (NAc) core in both male and female F1 mice, as indicated by the decreased c-Fos levels under mild stimulus. Of note, the activity of central nucleus of the amygdala (CeA) by mild stimulus was triggered in male but suppressed in female F1 mice, whereas the neurons of orbitofrontal cortex (OFC), cingulate cortex (Cg1), NAc shell, medial habenula (mHb), dorsal hippocampal CA1 (dCA1) and ventral hippocampal CA1 (vCA1) were only blunted in female F1 mice. Taken together, the distinct brain stimulation patterns between male and female F1 mice might contribute to the sex-specific behavioural outcomes by paternal METH exposure, which indicate that sex differences should be considered in the treatment of offspring paternally exposed drugs.

Temporal and spatial evolution of the distribution related to the number of COVID-19 pandemic.

This work systematically conducts a data analysis based on the numbers of both cumulative and daily confirmed COVID-19 cases and deaths in a time span through April 2020 to June 2022 for over 200 countries around the world. Such research feature aims to reveal the temporal and spatial evolution of the country-level distribution observed in COVID-19 pandemic, and obtains some interesting results as follows. (1) The distributions of the numbers for cumulative confirmed cases and deaths obey power-law in early stages of COVID-19 and stretched exponential function in subsequent course. (2) The distributions of the numbers for daily confirmed cases and deaths obey power-law in early and late stages of COVID-19 and stretched exponential function in middle stages. The crossover region between power-law and stretched exponential behavior seems to depend on the evolution of "infection" event and "death" event. Such observation implies a kind of important symmetry related to the dynamics process of COVID-19 spreading. (3) The distributions of the normalized numbers for each metric show a temporal scaling behavior in 2-year period, and are well described by stretched exponential function. The observation of power-law and stretched exponential behavior in such country-level distributions suggests underlying intrinsic dynamics of a virus spreading process in human interconnected society. And thus it is important for understanding and mathematically modeling the COVID-19 pandemic.

Precision Measurement of the Return Distribution Property of the Chinese Stock Market Index.

In econophysics, the analysis of the return distribution of a financial asset using statistical physics methods is a long-standing and important issue. This paper systematically conducts an analysis of composite index 1 min datasets over a 17-year period (2005−2021) for both the Shanghai and Shenzhen stock exchanges. To reveal the differences between Chinese and mature stock markets, we precisely measure the property of the return distribution of the composite index over the time scale Δt, which ranges from 1 min to almost 4000 min. The main findings are as follows: (1) The return distribution presents a leptokurtic, fat-tailed, and almost symmetrical shape that is similar to that of mature markets. (2) The central part of the return distribution is described by the symmetrical Lévy α-stable process, with a stability parameter comparable with a value of about 1.4, which was extracted for the U.S. stock market. (3) The return distribution can be described well by Student's t-distribution within a wider return range than the Lévy α-stable distribution. (4) Distinctively, the stability parameter shows a potential change when Δt increases, and thus a crossover region at 15 <Δt< 60 min is observed. This is different from the finding in the U.S. stock market that a single value of about 1.4 holds over 1 ≤Δt≤ 1000 min. (5) The tail distribution of returns at small Δt decays as an asymptotic power law with an exponent of about 3, which is a widely observed value in mature markets. However, it decays exponentially when Δt≥ 240 min, which is not observed in mature markets. (6) Return distributions gradually converge to a normal distribution as Δt increases. This observation is different from the finding of a critical Δt= 4 days in the U.S. stock market.

Multicomponent Crystals with Competing Intermolecular Interactions: In Situ X-ray Diffraction and Luminescent Features Reveal Multimolecular Assembly under Mechanochemical Conditions.

Supramolecular chemistry under mechanochemical conditions has drawn attention because it can induce low-solubility molecules to self-assemble, although most of the reported examples have been limited to two-component systems. We applied mechanochemical synthesis to achieve multimolecular self-assembly in more challenging three-component systems. The produced crystals showed multicolor solid-state luminescence depending on the components when exposed to UV light. Optical outputs and X-ray diffraction studies were used to examine the self-assembling behavior in greater depth. Using synchrotron radiation, in situ X-ray diffraction permitted direct observation of the milling process, which started the self-assembly process within 1 min. This research emphasizes the importance of multicomponent molecules with optical functions and self-assembling behavior and offers the possibility of developing more complicated multicomponent crystals and organic solid solutions for advanced materials.

The intragenic microRNA miR199A1 in the dynamin 2 gene contributes to the pathology of X-linked centronuclear myopathy.

Mutations in the myotubularin 1 (MTM1) gene can cause the fatal disease X-linked centronuclear myopathy (XLCNM), but the underlying mechanism is incompletely understood. In this report, using an Mtm1-/y disease model, we found that expression of the intragenic microRNA miR-199a-1 is up-regulated along with that of its host gene, dynamin 2 (Dnm2), in XLCNM skeletal muscle. To assess the role of miR-199a-1 in XLCNM, we crossed miR-199a-1-/- with Mtm1-/y mice and found that the resultant miR-199a-1-Mtm1 double-knockout mice display markers of improved health, as evidenced by lifespans prolonged by 30% and improved muscle strength and histology. Mechanistic analyses showed that miR-199a-1 directly targets nonmuscle myosin IIA (NM IIA) expression and, hence, inhibits muscle postnatal development as well as muscle maturation. Further analysis revealed that increased expression and phosphorylation of signal transducer and activator of transcription 3 (STAT3) up-regulates Dnm2/miR-199a-1 expression in XLCNM muscle. Our results suggest that miR-199a-1 has a critical role in XLCNM pathology and imply that this microRNA could be targeted in therapies to manage XLCNM.

GGPP depletion initiates metaflammation through disequilibrating CYB5R3-dependent eicosanoid metabolism.

Metaflammation is a primary inflammatory complication of metabolic disorders characterized by altered production of many inflammatory cytokines, adipokines, and lipid mediators. Whereas multiple inflammation networks have been identified, the mechanisms by which metaflammation is initiated have long been controversial. As the mevalonate pathway (MVA) produces abundant bioactive isoprenoids and abnormal MVA has a phenotypic association with inflammation/immunity, we speculate that isoprenoids from the MVA may provide a causal link between metaflammation and metabolic disorders. Using a line with the MVA isoprenoid producer geranylgeranyl diphosphate synthase (GGPPS) deleted, we find that geranylgeranyl pyrophosphate (GGPP) depletion causes an apparent metaflammation as evidenced by abnormal accumulation of fatty acids, eicosanoid intermediates, and proinflammatory cytokines. We also find that GGPP prenylate cytochrome b5 reductase 3 (CYB5R3) and the prenylated CYB5R3 then translocate from the mitochondrial to the endoplasmic reticulum (ER) pool. As CYB5R3 is a critical NADH-dependent reductase necessary for eicosanoid metabolism in ER, we thus suggest that GGPP-mediated CYB5R3 prenylation is necessary for metabolism. In addition, we observe that pharmacological inhibition of the MVA pathway by simvastatin is sufficient to inhibit CYB5R3 translocation and induces smooth muscle death. Therefore, we conclude that the dysregulation of MVA intermediates is an essential mechanism for metaflammation initiation, in which the imbalanced production of eicosanoid intermediates in the ER serve as an important pathogenic factor. Moreover, the interplay of MVA and eicosanoid metabolism as we reported here illustrates a model for the coordinating regulation among metabolite pathways.

TRAP1 suppresses oral squamous cell carcinoma progression by reducing oxidative phosphorylation metabolism of Cancer-associated fibroblasts.

BACKGROUND: Glucose metabolism in cancer associated fibroblasts (CAFs) within the tumor microenvironment is a material and energy source for tumorigenesis and tumor development. However, the characteristics and important regulatory mechanisms of glucose metabolism in fibroblasts associated with oral squamous cell carcinoma (OSCC) are still unknown. METHODS: We successfully isolated, cultured, purified and identified CAFs and normal fibroblasts (NFs). Cell culture, immunohistochemistry (IHC) and CCK8, flow cytometry, Seahorse XF Analyzer, MitoTracker assay, western blotting (WB), transmission electron microscope, Quantitative real-time PCR (qPCR), immunofluorescence (IF), and Label-free quantitative proteomics assay, animal xenograft model studies and statistical analysis were applied in this study. RESULTS: We demonstrated that the proliferation activity of CAFs was significantly enhanced as compared to NFs, while the apoptosis rate was significantly decreased. CAFs in OSCC preferentially use oxidative phosphorylation (OXPHOS) rather than glycolysis. Moreover, CAFs showed stronger maximal respiration, a larger substantial mitochondrial spare respiratory capacity (SRC) and higher adenosine triphosphate (ATP) production capacity than NFs. The results of mitotracker green fluorescence staining showed that compared with NFs, CAFs exhibited stronger green fluorescence. The results of WB showed the expression level of Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) obviously increased in CAFs compared to NFs. These results confirmed that CAFs have greater mitochondrial activity and function than NFs. Furthermore, Label-free quantitative proteomics assays showed that both ATP synthase subunit O (ATP5O) and tumor necrosis factor receptor-associated protein 1 (TRAP1) are important differentially expressed proteins in the mitochondria of CAFs/NFs. Overexpression of TRAP1 in CAFs increased basal oxygen consumption rate (OCR), maximal respiration, ATP production and SRC. In vivo, overexpression TRAP1 expression in CAFs suppress tumor growth. CONCLUSION: Taken together, the results indicated that TRAP1 is an important regulatory molecule of CAFs glucose metabolism and promotes OSCC progression by regulating the OXPHOS of CAFs.