The effects of exercise on FGF21 in adults: a systematic review and meta-analysis.

Background: Fibroblast growth factor 21 (FGF21) is a key hormone factor that regulates glucose and lipid homeostasis. Exercise may regulate its effects and affect disease states. Therefore, we sought to determine how exercise affects FGF21 concentrations in adults. Methods: The review was registered in the International Prospective Systematic Review (PROSPERO, CRD42023471163). The Cochrane Library, PubMed, and Web of Science databases were searched for studies through July 2023. Studies that assessed the effects of exercise training on FGF21 concentration in adults were included. The random effect model, data with standardized mean difference (SMD), and 95% confidence intervals (CI) were used to evaluate the pooled effect size of exercise training on FGF21. The risk of heterogeneity and bias were evaluated. A total of 12 studies involving 401 participants were included. Results: The total effect size was 0.3 (95% CI [-0.3-0.89], p = 0.33) when comparing participants who exercised to those who were sedentary. However, subgroup analysis indicated that concurrent exercise and a duration ≥10 weeks significantly decreased FGF21 concentrations with an effect size of -0.38 (95% CI [-0.74--0.01], p < 0.05) and -0.38 (95% CI [-0.63--0.13], p < 0.01), respectively. Conclusion: Concurrent exercise and longer duration may be more efficient way to decrease FGF21 concentrations in adults with metabolic disorder.

Temporal Convolutional Neural Network-Based Prediction of Vascular Health in Elderly Women Using Photoplethysmography-Derived Pulse Wave during Exercise.

(1) Background: The objective of this study was to predict the vascular health status of elderly women during exercise using pulse wave data and Temporal Convolutional Neural Networks (TCN); (2) Methods: A total of 492 healthy elderly women aged 60-75 years were recruited for the study. The study utilized a cross-sectional design. Vascular endothelial function was assessed non-invasively using Flow-Mediated Dilation (FMD). Pulse wave characteristics were quantified using photoplethysmography (PPG) sensors, and motion-induced noise in the PPG signals was mitigated through the application of a recursive least squares (RLS) adaptive filtering algorithm. A fixed-load cycling exercise protocol was employed. A TCN was constructed to classify flow-mediated dilation (FMD) into "optimal", "impaired", and "at risk" levels; (3) Results: TCN achieved an average accuracy of 79.3%, 84.8%, and 83.2% in predicting FMD at the "optimal", "impaired", and "at risk" levels, respectively. The results of the analysis of variance (ANOVA) comparison demonstrated that the accuracy of the TCN in predicting FMD at the impaired and at-risk levels was significantly higher than that of Long Short-Term Memory (LSTM) networks and Random Forest algorithms; (4) Conclusions: The use of pulse wave data during exercise combined with the TCN for predicting the vascular health status of elderly women demonstrated high accuracy, particularly in predicting impaired and at-risk FMD levels. This indicates that the integration of exercise pulse wave data with TCN can serve as an effective tool for the assessment and monitoring of the vascular health of elderly women.

[Clinical efficacy of nusinersen sodium in the treatment of children with spinal muscular atrophy]. / è¯ºè¥¿é‚£ç”Ÿé’ æ²»ç–—è„Šé«“æ€§è‚ŒèŽç¼©ç—‡å„¿ç«¥çš„ä¸´åºŠåˆ†æž.

OBJECTIVES: To investigate the efficacy and safety of nusinersen sodium in the treatment of children with spinal muscular atrophy (SMA). METHODS: A retrospective analysis was conducted on the clinical data of 50 children with 5q SMA who received nusinersen sodium treatment and multidisciplinary treatment management in Shanxi Children's Hospital from February 2022 to February 2024. RESULTS: Compared with the baseline data, 67% (8/12), 74% (35/47), and 74% (35/47) of the SMA children had a clinically significant improvement in the scores of Philadelphia Infant Test of Neuromuscular Disorders, Hammersmith Functional Motor Scale Expanded, and Revised Upper Limb Module, respectively, and the distance of 6-minute walking test increased from 207.00 (179.00, 281.50) meters to 233.00 (205.25, 287.50) meters (P<0.05) after nusinersen sodium treatment. Of all 50 children with SMA, 24 (48%) showed good tolerability after administration, with no significant or persistent abnormalities observed in 2 034 laboratory test results, and furthermore, there were no serious or immunological adverse events related to the treatment. After treatment, there was a significant change in forced vital capacity as a percentage of the predicted value in 27 children with restrictive ventilatory dysfunction, as well as a significant change in the level of 25-(OH) vitamin D in 15 children with vitamin D deficiency (P<0.05). CONCLUSIONS: For children with SMA, treatment with nusinersen sodium can continuously improve the response rates of motor function scales, with good tolerability and safety.

A new tau dephosphorylation-targeting chimera for the treatment of tauopathies.

Abnormal accumulation of hyperphosphorylated tau protein plays a pivotal role in a collection of neurodegenerative diseases named tauopathies, including Alzheimer's disease (AD). We have recently conceptualized the design of hetero-bifunctional chimeras for selectively promoting the proximity between tau and phosphatase, thus specifically facilitating tau dephosphorylation and removal. Here, we sought to optimize the construction of tau dephosphorylating-targeting chimera (DEPTAC) and obtained a new chimera D14, which had high efficiency in reducing tau phosphorylation both in cell and tauopathy mouse models, while showing limited cytotoxicity. Moreover, D14 ameliorated neurodegeneration in primary cultured hippocampal neurons treated with toxic tau-K18 fragments, and improved cognitive functions of tauopathy mice. These results suggested D14 as a cost-effective drug candidate for the treatment of tauopathies.

Quantitative assessment of colour fundus photography in hyperopia children based on artificial intelligence.

OBJECTIVES: This study aimed to quantitatively evaluate optic nerve head and retinal vascular parameters in children with hyperopia in relation to age and spherical equivalent refraction (SER) using artificial intelligence (AI)-based analysis of colour fundus photographs (CFP). METHODS AND ANALYSIS: This cross-sectional study included 324 children with hyperopia aged 3-12 years. Participants were divided into low hyperopia (SER+0.5 D to+2.0 D) and moderate-to-high hyperopia (SER≥+2.0 D) groups. Fundus parameters, such as optic disc area and mean vessel diameter, were automatically and quantitatively detected using AI. Significant variables (p<0.05) in the univariate analysis were included in a stepwise multiple linear regression. RESULTS: Overall, 324 children were included, 172 with low and 152 with moderate-to-high hyperopia. The median optic disc area and vessel diameter were 1.42 mm2 and 65.09 µm, respectively. Children with high hyperopia had larger superior neuroretinal rim (NRR) width and larger vessel diameter than those with low and moderate hyperopia. In the univariate analysis, axial length was significantly associated with smaller superior NRR width (ß=-3.030, p<0.001), smaller temporal NRR width (ß=-1.469, p=0.020) and smaller vessel diameter (ß=-0.076, p<0.001). A mild inverse correlation was observed between the optic disc area and vertical disc diameter with age. CONCLUSION: AI-based CFP analysis showed that children with high hyperopia had larger mean vessel diameter but smaller vertical cup-to-disc ratio than those with low hyperopia. This suggests that AI can provide quantitative data on fundus parameters in children with hyperopia.

Sparse reconstruction of sound field using pattern-coupled Bayesian compressive sensing.

Conventional near-field acoustic holography based on compressive sensing either does not fully exploit the underlying block-sparse structures of the signal or suffers from a mismatch between the actual and predefined block structure due to the lack of prior information about block partitions, resulting in poor accuracy in sound field reconstruction. In this paper, a pattern-coupled Bayesian compressive sensing method is proposed for sparse reconstruction of sound fields. The proposed method establishes a hierarchical Gaussian-Gamma probability model with a pattern-coupled prior based on the equivalent source method, transforming the sound field reconstruction problem into recovering the sparse coefficient vector of the equivalent source strengths within the compressive sensing framework. A set of hyperparameters is introduced to control the sparsity of each element in the sparse coefficient vector of the equivalent source strengths, where the sparsity of each element is determined by both its own hyperparameters and those of its immediate neighbors. This approach enables the promotion of block sparse solutions and achieves better performance in solving for the sparse coefficient vector of the equivalent source strengths without prior information of block partitions. The effectiveness and superiority of the proposed method in reconstructing sound fields are verified by simulations and experiments.

Neoadjuvant sintilimab plus chemotherapy in EGFR-mutant NSCLC: Phase 2 trial interim results (NEOTIDE/CTONG2104).

The clinical efficacy of neoadjuvant immunotherapy plus chemotherapy remains elusive in localized epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). Here, we report interim results of a Simon's two-stage design, phase 2 trial using neoadjuvant sintilimab with carboplatin and nab-paclitaxel in resectable EGFR-mutant NSCLC. All 18 patients undergo radical surgery, with one patient experiencing surgery delay. Fourteen patients exhibit confirmed radiological response, with 44% achieving major pathological response (MPR) and no pathological complete response (pCR). Similar genomic alterations are observed before and after treatment without influencing the efficacy of subsequent EGFR-tyrosine kinase inhibitors (TKIs) in vitro. Infiltration and T cell receptor (TCR) clonal expansion of CCR8+ regulatory T (Treg)hi/CXCL13+ exhausted T (Tex)lo cells define a subtype of EGFR-mutant NSCLC highly resistant to immunotherapy, with the phenotype potentially serving as a promising signature to predict immunotherapy efficacy. Informed circulating tumor DNA (ctDNA) detection in EGFR-mutant NSCLC could help identify patients nonresponsive to neoadjuvant immunochemotherapy. These findings provide supportive data for the utilization of neoadjuvant immunochemotherapy and insight into immune resistance in EGFR-mutant NSCLC.

Effects of short-term supplementation with DHA-enriched phosphatidylcholine and phosphatidylserine on lipid profiles in the brain and liver of n-3 PUFA-deficient mice in early life after weaning.

BACKGROUND: Lack of n-3 polyunsaturated fatty acids during the period of maternity drastically lowers the docosahexaenoic acid (DHA) level in the brain of offspring and studies have demonstrated that different molecular forms of DHA are beneficial to brain development. The aim of this study was to investigate the effect of short-term supplementation with DHA-enriched phosphatidylserine (PS) and phosphatidylcholine (PC) on DHA levels in the liver and brain of congenital n-3-deficient mice. RESULTS: Dietary supplementation with DHA significantly changed the fatty acid composition of various phospholipid molecules in the cerebral cortex and liver while DHA-enriched phospholipid was more effective than DHA triglyceride (TG) in increasing brain and liver DHA. Both DHA-PS and DHA-PC could effectively increase the DHA levels, but DHA in the PS form was superior to PC in the contribution of DHA content in the brain ether-linked PC (ePC) and liver lyso-phosphatidylcholine molecular species. DHA-PC showed more significant effects on the increase of DHA in liver TG, PC, ePC, phosphatidylethanolamine (PE) and PE plasmalogen (pPE) molecular species and decreasing the arachidonic acid level in liver PC plasmalogen, ePC, PE and pPE molecular species compared with DHA-PS. CONCLUSION: The effect of dietary interventions with different molecular forms of DHA for brain and liver lipid profiles is different, which may provide theoretical guidance for dietary supplementation of DHA for people. © 2024 Society of Chemical Industry.

The AaERF64-AaTPPA module participates in cold acclimatization of Actinidia arguta (Sieb. et Zucc.) Planch ex Miq.

Actinidia arguta (A. arguta, kiwiberry) is a perennial deciduous vine with a strong overwintering ability. We hypothesized that trehalose metabolism, which plays a pivotal role in the stress tolerance of plants, may be involved in the cold acclimatization of A. arguta. Transcriptome analysis showed that the expression of AaTPPA, which encodes a trehalose-6-phosphate phosphatase (TPP), was upregulated in response to low temperatures. AaTPPA expression levels were much higher in lateral buds, roots, and stem cambia than in leaves in autumn. In AaTPPA-overexpressing (OE) Arabidopsis thaliana (A. thaliana), trehalose levels were 8-11 times higher than that of the wild type (WT) and showed different phenotypic characteristics from WT and OtsB (Escherichia coli TPP) overexpressing lines. AaTPPA-OE A. thaliana exhibited significantly higher freezing tolerance than WT and OtsB-OE lines. Transient overexpression of AaTPPA in A. arguta leaves increased the scavenging ability of reactive oxygen species (ROS) and the soluble sugar and proline contents. AaERF64, an ethylene-responsive transcription factor, was induced by ethylene treatment and bound to the GCC-box of the AaTPPA promoter to activate its expression. AaTPPA expression was also induced by abscisic acid. In summary, the temperature decrease in autumn is likely to induce AaERF64 expression through an ethylene-dependent pathway, which consequently upregulates AaTPPA expression, leading to the accumulation of osmotic protectants such as soluble sugars and proline in the overwintering tissues of A. arguta. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01475-8.

Development of apple pectin/soy protein isolate-based edible films containing punicalagin for strawberry preservation.

In this study, we developed punicalagin-loaded antimicrobial films based on soy protein isolate (SPI) and apple pectin (AP). The AP was derived from apple pomace waste while the punicalagin was obtained from pomegranate peel. Punicalagin was identified to exist in both α- and ß-isomers, with the ß-type being predominant. The composite films were characterized using scanning electron microscopy, Fourier transformed infrared spectroscopy, X-ray diffraction, and thermogravimetric analysis. Our results demonstrated that the incorporation of AP significantly enhanced the mechanical strength, heat resistance, and barrier properties of the films. Moreover, the composite films integrated with punicalagin exhibited excellent antimicrobial activities against Staphylococcus aureus (with a minimum bactericidal concentration value of 0.25 %), Escherichia coli (with a minimum bactericidal concentration value of 0.50 %), and Aspergillus niger. Finally, these antimicrobial film solutions were tested as coatings on strawberries and found to have significantly better effects on reducing weight loss, improving shelf-life, and maintaining the freshness of strawberries compared to coatings without punicalagin. The results indicate that antimicrobial coatings loaded with punicalagin hold great promise as multifunctional active packaging materials for fruit preservation.

The ArgR-Regulated ADI Pathway Facilitates the Survival of Vibrio fluvialis under Acidic Conditions.

Vibrio fluvialis is an emerging foodborne pathogenic bacterium that can cause severe cholera-like diarrhea and various extraintestinal infections, posing challenges to public health and food safety worldwide. The arginine deiminase (ADI) pathway plays an important role in bacterial environmental adaptation and pathogenicity. However, the biological functions and regulatory mechanisms of the pathway in V. fluvialis remain unclear. In this study, we demonstrate that L-arginine upregulates the expression of the ADI gene cluster and promotes the growth of V. fluvialis. The ADI gene cluster, which we proved to be comprised of two operons, arcD and arcACB, significantly enhances the survival of V. fluvialis in acidic environments both in vitro (in culture medium and in macrophage) and in vivo (in mice). The mRNA level and reporter gene fusion analyses revealed that ArgR, a transcriptional factor, is necessary for the activation of both arcD and arcACB transcriptions. Bioinformatic analysis predicted the existence of multiple potential ArgR binding sites at the arcD and arcACB promoter regions that were further confirmed by electrophoretic mobility shift assay, DNase I footprinting, or point mutation analyses. Together, our study provides insights into the important role of the ArgR-ADI pathway in the survival of V. fluvialis under acidic conditions and the detailed molecular mechanism. These findings will deepen our understanding of how environmental changes and gene expression interact to facilitate bacterial adaptations and virulence.

POLM variant G312R promotes ovarian tumorigenesis through genomic instability and COL11A1-NF-κB axis.

In ovarian cancer (OC), identifying key molecular players in disease escalation and chemoresistance remains critical. Our investigation elucidates the role of the DNA polymerase mu (POLM), especially G312R mutation, in propelling oncogenesis through dual pathways. POLMG312R markedly augments the ribonucleotide insertion capability of POLM, precipitating genomic instability. In addition, our research reveals that POLMG312R perturbs collagen alpha-1 (XI) chain (COL11A1) expression-a gene that plays a key role in oncogenesis-and modulates the NF-κB signaling pathway, alters the secretion of downstream inflammatory cytokines, and promotes tumor-macrophage interactions. We illustrate a bidirectional regulatory interaction between POLM, particularly its G312R variant, and COL11A1. This interaction regulates NF-κB signaling, culminating in heightened malignancy and resistance to chemotherapy in OC cells. These insights position the POLM as a potential molecular target for OC therapy, shedding light on the intricate pathways underpinning POLM variant disease progression.NEW & NOTEWORTHY Our research reveals that POLM plays an important role in ovarian cancer development, especially the mutation G312R. We uncover the POLMG312R mutation as a driver of genomic instability in ovarian cancer via aberrant ribonucleotide incorporation. We reveal that POLMG312R upregulates COL11A1 and activates NF-κB signaling, contributing to tumor progression and chemoresistance. This study identifies the POLM-COL11A1-NF-κB axis as a novel oncogenic pathway.

Long-Term Protection against Virulent Newcastle Disease Virus (NDV) in Chickens Immunized with a Single Dose of Recombinant Turkey Herpesvirus Expressing NDV F Protein.

Newcastle disease (ND) is a significant infectious disease in poultry, causing substantial economic losses in developing countries. To control ND, chickens must be vaccinated multiple times a year. In order to develop an improved vaccine that provides long-term protection, the F gene from genotype VII NDV was inserted into the herpesvirus of turkey (HVT) vaccine virus using CRISPR/Cas9-mediated NHEJ repair and Cre/LoxP technology. The immunogenicity and protective efficacy of the resulting recombinant vaccines were evaluated through antibody assays and virus challenge experiments. Two recombinant vaccines, rHVT-005/006-F and rHVT-US2-F, were generated, both exhibiting growth rates comparable with those of HVT in vitro and consistently expressing the F protein. One-day-old specific pathogen-free (SPF) chickens immunized with 2000 PFU/bird of either rHVT-005/006-F or rHVT-US2-F developed robust humoral immunity and were completely protected against challenge with the NDV F48E8 strain at 4 weeks post-vaccination (wpv). Furthermore, a single dose of these vaccines provided sustained protection for at least 52 wpv. Our study identifies rHVT-005/006-F and rHVT-US2-F as promising ND vaccine candidates, offering long-term protection with a single administration. Moreover, HVT-005/006 demonstrates promise for accommodating additional foreign genes, facilitating the construction of multiplex vaccines.

Association between plasma growth differentiation factor 15 levels and pre-eclampsia in China.

Background: Growth differentiation factor-15 (GDF-15) is a stress response protein and is related to cardiovascular diseases (CVD). This study aimed to investigate the association between GDF-15 and pre-eclampsia (PE). Method: The study involved 299 pregnant women, out of which 236 had normal pregnancies, while 63 participants had PE. Maternal serum levels of GDF-15 were measured by using enzyme-linked immunosorbent assay kits and then translated into multiple of median (MOM) to avoid the influence of gestational week at blood sampling. Logistic models were performed to estimate the association between GDF-15 MOM and PE, presenting as odd ratios (ORs) and 95% confidence intervals (CIs). Results: MOM of GDF-15 in PE participants was higher compared with controls (1.588 vs. 1.000, p < 0.001). In the logistic model, pregnant women with higher MOM of GDF-15 (>1) had a 4.74-fold (95% CI = 2.23-10.08, p < 0.001) increased risk of PE, adjusted by age, preconceptional body mass index, gravidity, and parity. Conclusions: These results demonstrated that higher levels of serum GDF-15 were associated with PE. GDF-15 may serve as a biomarker for diagnosing PE.

Direct injection ultra-performance liquid chromatography-tandem mass spectrometry for the high-throughput determination of etomidate and etomidate acid in wastewater.

Etomidate (ET), a hypnotic agent used for the induction of anesthesia, is rapidly metabolized to etomidate acid (ETA) in the liver. Recently, ET has become one of the most serious alternative drugs of abuse in China. Therefore, an urgent need exists to develop a fast and convenient analysis method for monitoring ET. The current work presents a simple, fast, and sensitive direct injection method for the determination of ET and ETA in wastewater. After the optimization of the ultra-performance liquid chromatography-tandem mass spectrometry and sample filtration conditions, the method exhibited satisfactory limits of detection (1 ng/L) and good filtration loss. The validated method was successfully applied to determine the concentrations of ET and ETA in wastewater samples (n = 245) from several wastewater treatment plants in China. The concentrations of the targets in positive samples ranged from less than the lower limits of quantitation to 47.71 ng/L. The method can meet ET monitoring and high-throughput analysis requirements.

Rate and predictors of postoperative opioid use and high opioid exposure after surgery in New Zealand: a retrospective study.

BACKGROUND: Although excessive opioid use is a significant global health issue, there is a lack of literature on the prescribing patterns for postoperative opioid use and exposure after discharge among surgical patients. This study aimed to examine the rate and predictors of opioid dispensing and high opioid exposure after hospital discharge from surgery in New Zealand (NZ) between January 2007 to December 2019. METHODS: This is a retrospective population-based cohort study inclusive of all ages and surgical specialties. Data were obtained from the NZ Ministry of Health's national health databases. RESULTS: 1 781 059 patients were included in the study and 20.9% (n = 371 882) of surgical patients received opioids within 7 days after hospital discharge. From those who were dispensed with opioids after hospital discharge, 36.6% (n = 134 646) had high opioid exposure. Orthopaedic surgery (AOR 6.97; 95% CI 6.82-7.13) and history of opioid use (AOR 3.18; 95% CI 2.86-3.53) increased the odds of postoperative opioid dispensing and high opioid exposure respectively. Severe multi-morbidity burden (AOR 0.76; 95% CI 0.73-0.78) and alcohol misuse (AOR 0.84; 95% CI 0.77-0.93) lowered the odds of postoperative opioid dispensing and high opioid exposure respectively. CONCLUSIONS: Our findings suggest a concerning rate of high opioid exposure among surgical patients after discharge. The predictors for postoperative opioid dispensing and high opioid exposure identified in our study provide insight into opioid prescribing patterns in NZ and inform future postoperative pain management.

Resource regulation and green innovation: Evidence from China's water rights trading policy.

Green innovation is the pivotal part connected with achieving urban sustainable development. Resource regulation, represented by water rights trading policy (WRTP), is playing an increasingly important role in supporting urban green innovation (UGI). Therefore, this paper uses the WRTP conducted in 2014 in China as a quasi-natural experiment to evaluate the net effect of resource regulation on green innovation by the identification methods of difference-in-differences (DID) model. The results show that: (1) WRTP promotes UGI significantly, and this finding holds after a series of robustness tests. (2)The influencing mechanisms are mainly by optimizing industrial structure and enhancing the efficiency of resource allocation and information exchange efficiency and the promoting function is moderated by urban competitiveness and population agglomeration. (3) The promotion effects are greater in cities with higher level of government intervention, environmental pollution, water using quantity and local economy.(4) WRTP has the spatial spillover effect on UGI. These findings provide insights into sustainable development of water resources, management of water trading market, urban green innovation and sustainable economic development.

A molecularly imprinted ratiometric fluorescent sensor for visual detection of 1-naphthol based on fluorescence-enhanced CdTeS QDs via APTES modification.

CdTeS quantum dots (CdTeS QDs) were synthesized using the hydrothermal method and subsequently modified with (3-aminopropyl)triethoxysilane (APTES). This modification resulted in a significant enhancement of the fluorescence intensity, which was observed to be five times stronger than that of unmodified CdTeS QDs at 597 nm. Only after the fluorescence enhancement by APTES modification, the material showed a response to 1-naphthol (1-NP). Based on this, the molecularly imprinted polymers (MIPs) with ratiometric fluorescence were developed for the detection of 1-NP, that is, the synthetic raw material and the metabolite of the pesticide carbaryl. Under the excitation of 365 nm UV, the bright orange-red fluorescence (597 nm) of CdTeS QDs encapsulated in MIPs was quenched by 1-NP in the suspension, and 1-NP showed a gradually increasing blue emission (460 nm) with the increase of its concentration. This sensor has a good linear relationship between fluorescence intensity ratio (F460/F597) and 1-NP concentration (C1-NP) in a large concentration range (6.0-140.0 µM, LOD=0.45 µM, RSD<4.41%). It exhibits a visible fluorescence change from orange-red to blue-purple. Excellent recoveries in real samples were obtained by simulating carbaryl metabolism and demonstrated its potential in detection of 1-NP and carbaryl.

TRIM65 promotes renal cell carcinoma through ubiquitination and degradation of BTG3.

As a typical E3 ligase, TRIM65 (tripartite motif containing 65) is involved in the regulation of antiviral innate immunity and the pathogenesis of certain tumors. However, the role of TRIM65 in renal cell carcinoma (RCC) and the underlying mechanism has not been determined yet. In this study, we identified TRIM65 as a novel oncogene in RCC, which enhanced the tumor cell proliferation and anchorage-independent growth abilities both in vitro and in vivo. Moreover, we found that TRIM65-regulated RCC proliferation mainly via direct interaction with BTG3 (BTG anti-proliferation factor 3), which in turn induced the K48-linked ubiquitination and subsequent degradation through K41 amino acid. Furthermore, TRIM65 relieved G2/M phase cell cycle arrest via degradation of BTG3 and regulated downstream factors. Further studies revealed that TRIM65 acts through TRIM65-BTG3-CyclinD1 axis and clinical sample IHC chip data indicated a negative correction between TRIM65 and BTG3. Taken together, our findings demonstrated that TRIM65 promotes RCC cell proliferation via regulation of the cell cycle through degradation of BTG3, suggesting that TRIM65 may be a promising target for RCC therapy.