Long-term motor training enhances functional connectivity between semantic and motor regions in an effector-specific manner: evidence from elite female football athletes.

The relation between the action verb semantic processing and sensorimotor experience remains controversial. In this study, we examined whether plasticity changes in brain are specifically related to semantic processing of foot action verbs when long-term motor training is mainly aimed at the foot. To address this question, we acquired resting-state functional magnetic resonance imaging scans and behavioral data from a verb two-choice task from female expertise football players and football novices. We compared the resting-state functional connectivity (rsFC) differences between experts and novices using motor execution regions and general semantic regions (left anterior temporal lobe, lATL) as seed, and explored the neural correlates of behavioral performance. Here, the drift rate (v) parameter of the drift diffusion model (DDM) was used to capture the semantic processing capability. We found experts showed increased correlation between lATL subregions and important brain regions for motor processing, including supplementary motor area (SMA), bilateral paracentral lobule (PL), superior parietal lobule and inferior parietal lobule, in contrast to novices. Further predictive model analysis showed the FC found in rsFC analysis can significantly predict drift rate of foot action verb in both experts and novices, but not drift rate of hand action verb. Our findings therefore establish a connection between effector-related semantic processing and the plasticity changes in brain functional connectivity, attributable to long-term foot-related motor training. This provides evidence supporting the view that semantic processing is fundamentally rooted in the sensorimotor system.

Discovery of novel RNA viruses through analysis of fungi-associated next-generation sequencing data.

BACKGROUND: Like all other species, fungi are susceptible to infection by viruses. The diversity of fungal viruses has been rapidly expanding in recent years due to the availability of advanced sequencing technologies. However, compared to other virome studies, the research on fungi-associated viruses remains limited. RESULTS: In this study, we downloaded and analyzed over 200 public datasets from approximately 40 different Bioprojects to explore potential fungal-associated viral dark matter. A total of 12 novel viral sequences were identified, all of which are RNA viruses, with lengths ranging from 1,769 to 9,516 nucleotides. The amino acid sequence identity of all these viruses with any known virus is below 70%. Through phylogenetic analysis, these RNA viruses were classified into different orders or families, such as Mitoviridae, Benyviridae, Botourmiaviridae, Deltaflexiviridae, Mymonaviridae, Bunyavirales, and Partitiviridae. It is possible that these sequences represent new taxa at the level of family, genus, or species. Furthermore, a co-evolution analysis indicated that the evolutionary history of these viruses within their groups is largely driven by cross-species transmission events. CONCLUSIONS: These findings are of significant importance for understanding the diversity, evolution, and relationships between genome structure and function of fungal viruses. However, further investigation is needed to study their interactions.

Effects of chronic aerobic exercise on attentional bias among women with methamphetamine addiction.

Objective: To explore the effects of chronic exercise on attentional bias toward drug-related stimuli and on brain electrophysiological characteristics among women with methamphetamine addiction. Methods: In total, 63 women with methamphetamine addiction were randomized to participate in a dance (n = 21; mean age, 32.16 ± 2.07 years), bicycle (n = 21; mean age, 32.59 ± 2.12 years), or control (maintained regular activities with little exercise; n = 21; mean age, 30.95 ± 2.81 years) group for 12 weeks. The participants in the three groups were not significantly different in terms of methamphetamine use or detoxification. Before and after the intervention, attentional bias was assessed using the dot-probe task, and event-related potentials were recorded during the task. Results: The mean attentional bias scores decreased significantly after the intervention in both exercise groups but not in the control group. After 12 weeks of dance exercise, the amplitudes of the N170, N2, P2, and P3 components of the event-related potentials decreased significantly during attentional bias processing. In addition, differences in N170 amplitudes for congruent vs. incongruent conditions in the dot-probe task were no longer observed. After 12 weeks of cycling exercise, N2 and P2 amplitudes decreased significantly. By contrast, there were no significant differences in N170, N2, P2, and P3 amplitudes in the control group before vs. after the intervention. Conclusions: Chronic (12 weeks of) aerobic exercise reduced attentional bias toward drug-related cues by improving attentional inhibition and reducing the maintenance of extra attention to drug-related cues among women with methamphetamine addiction. Both dance and bicycle exercise improved the early recognition of drug-related cues, weakened the influence of the memory of previous drug use, and improved attentional bias behavior by strengthening attention control. Dance exercise, but not bicycling, also regulated emotional control and improved the attention selection process. These results provide theoretical and empirical evidence that chronic aerobic exercise may reduce the attentional bias toward drug-related cues to assist in the recovery of women with methamphetamine addiction.

Proteomic Landscape Associated with Cognitive Impairment in Individuals with Long-term Methamphetamine Dependence.

BACKGROUND: Methamphetamine (METH) is a highly addictive drug that directly affects the central nervous system. METH use not only harms the user's health but also poses risks and costs to society. Prolonged METH dependence has been shown to impair cognition, which may be the primary factor in impulsive drug-seeking behaviors and high relapse rates. However, the molecular mechanisms underlying METH addiction and METH-induced cognitive decline remain poorly understood. METHODS: To illuminate the potential molecular mechanisms underpinning METH addiction, we compared serum protein expression levels between 12 long-term METH users and 12 healthy controls using label-free quantitative proteomics. Bioinformatic analyses were conducted to determine functional networks and protein-protein interactions. RESULTS: In total, 23 differentially expressed proteins were identified between the two groups. The differentially expressed proteins were related to cognitive dysfunction, neuroinflammation, immune impairment, metabolic disturbances, and calcium binding and regulation. CONCLUSIONS: These 23 proteins may underpin the multi-system damage induced by chronic METH exposure. Our findings provide novel insights into the molecular basis of METH addiction and inform potential prevention and treatment strategies for individuals with METH dependence.

Mechanisms of Action Anticipation in Table Tennis Players: A Multivoxel Pattern Analysis Study.

An exceptional ability to accurately anticipate an opponent's action is paramount for competitive athletes and highlights their experiential mastery. Despite conventional associations of action observation with specific brain regions, neuroimaging discrepancies persist. To explore the brain regions and neural mechanisms undergirding action anticipation, we compared distinct brain activation patterns involved in table tennis serve anticipation of expert table tennis athletes vs. non-experts by using both univariate analysis and multivoxel pattern analysis (MVPA). We collected functional magnetic resonance imaging data from 29 table tennis experts and 34 non-experts as they pressed a button to predict the trajectory of a ball in a table tennis serve video truncated at the moment of racket-ball contact vs. pressing any button while viewing a static image of the first video frame. MVPA was applied to assess whether it could accurately differentiate experts from non-experts. MVPA results indicated moderate accuracy (90.48%) for differentiating experts from non-experts. Brain regions contributing most to the differentiation included the left cerebellum, the vermis, the right middle temporal pole, the inferior parietal cortex, the bilateral paracentral lobule, and the left supplementary motor area. The findings suggest that brain regions associated with cognitive conflict monitoring and motor cognition contribute to the action anticipation ability of expert table tennis players.

A taxonomic study of the Platydracus brachycerus group with descriptions of three new species from China (Coleoptera: Staphylinidae, Staphylininae).

We here propose a species group within the genus Platydracus, the brachycerus group, that is very likely associated with termites and includes three known species: Platydracus brachycerus Smetana & Davies, 2000; Platydracus juang Smetana, 2005; and Platydracus donnyi Rougemont, 2015. We also describe three new species belonging to this group, all from China: P. smetanai sp. n. (Zhejiang, Anhui, Hunan, Guangxi), P. gracilis sp. n. (Guangxi) and P. paragracilis sp. n. (Yunnan). Platydracus juang is newly recorded from Hunan, Guangxi, Guangdong and Hainan provinces. A key to species of the Platydracus brachycerus group is provided.

Aerobic exercise promotes emotion regulation: a narrative review.

Aerobic exercise improves the three stages of emotion regulation: perception, valuation and action. It reduces the perception of negative emotions, encourages individuals to reinterpret emotional situations in a positive or non-emotional manner, and enhances control over emotion expression behaviours. These effects are generated via increased prefrontal cortex activation, the strengthening of functional connections between the amygdala and several other brain regions, and the enhancement of the plasticity of key emotion regulation pathways and nodes, such as the uncinate fasciculus. The effect of aerobic exercise on emotion regulation is influenced by the exercise intensity and duration, and by individuals' exercise experience. Future research may explore the key neural basis of aerobic exercise's promotion of emotion regulation.

Gastric cancer mesenchymal stem cells promote tumor glycolysis and chemoresistance by regulating B7H3 in gastric cancer cells.

Despite surgical treatment combined with multidrug therapy having made some progress, chemotherapy resistance is the main cause of recurrence and death of gastric cancer (GC). Gastric cancer mesenchymal stem cells (GCMSCs) have been reported to be correlated with the limited efficacy of chemotherapy in GC, but the mechanism of GCMSCs regulating GC resistance needs to be further studied. The gene set enrichment analysis (GSEA) was performed to explore the glycolysis-related pathways heterogeneity across different cell subpopulations. Glucose uptake and lactate production assays were used to evaluate the importance of B7H3 expression in GCMSCs-treated GC cells. The therapeutic efficacy of oxaliplatin (OXA) and paclitaxel (PTX) was determined using CCK-8 and colony formation assays. Signaling pathways altered by GCMSCs-CM were revealed by immunoblotting. The expression of TNF-α in GCMSCs and bone marrow mesenchymal stem cells (BMMSCs) was detected by western blot analysis and qPCR. Our results showed that the OXA and PTX resistance of GC cells were significantly enhanced in the GCMSCs-CM treated GC cells. Acquired OXA and PTX resistance was characterized by increased cell viability for OXA and PTX, the formation of cell colonies, and decreased levels of cell apoptosis, which were accompanied by reduced levels of cleaved caspase-3 and Bax expression, and increased levels of Bcl-2, HK2, MDR1, and B7H3 expression. Blocking TNF-α in GCMSCs-CM, B7H3 knockdown or the use of 2-DG, a key enzyme inhibitor of glycolysis in GC cells suppressed the OXA and PTX resistance of GC cells that had been treated with GCMSCs-CM. This study shows that GCMSCs-CM derived TNF-α could upregulate the expression of B7H3 of GC cells to promote tumor chemoresistance. Our results provide a new basis for the treatment of GC.

Altered neurovascular coupling in migraine without aura.

Neurovascular coupling (NVC) provides new insights into migraine, a neurological disorder impacting over one billion people worldwide. This study compared NVC and cerebral blood flow (CBF) in patients with migraine without aura (MwoA) and healthy controls. About 55 MwoA patients in the interictal phase and 40 age- and sex-matched healthy controls underwent resting-state functional magnetic resonance imaging and arterial spin-labeling perfusion imaging scans. The CBF and resting-state neuronal activity indicators, including the amplitudes of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), and degree centrality (DC), were calculated for each participant. The global and regional NVCs were assessed using cross-voxel CBF-neuronal activity correlations and CBF/neuronal activity ratios. Patients with MwoA showed increased CBF/ALFF ratios in the left media, superior and inferior frontal gyri, and anterior cingulate gyrus, increased CBF/DC ratios in the left middle and inferior frontal gyri, and increased CBF/ReHo ratios in the right corpus callosum and right posterior cingulate gyrus. Lower CBF/ALFF ratios in the right rectal gyrus, the left orbital gyrus, the right inferior frontal gyrus, and the right superior temporal gyrus were also found in the MwoA patients. Furthermore, the CBF/ALFF ratios in the inferior frontal and superior temporal gyri were positively correlated with the Headache Impact Test scores and Hamilton anxiety scale scores in the MwoA patients. These findings provide evidence for the theory that abnormal NVC contributes to MwoA.

fMRI evidence of movement familiarization effects on recognition memory in professional dancers.

Dual-process theories propose that recognition memory involves recollection and familiarity; however, the impact of motor expertise on memory recognition, especially the interplay between familiarity and recollection, is relatively unexplored. This functional magnetic resonance imaging study used videos of a dancer performing International Latin Dance Styles as stimuli to investigate memory recognition in professional dancers and matched controls. Participants observed and then reported whether they recognized dance actions, recording the level of confidence in their recollections, whereas blood-oxygen-level-dependent signals measured encoding and recognition processes. Professional dancers showed higher accuracy and hit rates for high-confidence judgments, whereas matched controls exhibited the opposite trend for low-confidence judgments. The right putamen and precentral gyrus showed group-based moderation effects, especially for high-confidence (vs. low-confidence) action recognition in professional dancers. During action recognition, the right superior temporal gyrus and insula showed increased activation for accurate recognition and high-confidence retrieval, particularly in matched controls. These findings highlighting enhanced action memory of professional dancers-evident in their heightened recognition confidence-not only supports the dual-processing model but also underscores the crucial role of expertise-driven familiarity in bolstering successful recollection. Additionally, they emphasize the involvement of the action observation network and frontal brain regions in facilitating detailed encoding linked to intention processing.

A systematic review and meta-analysis of the effects of physical exercise on white matter integrity and cognitive function in older adults.

In the context of a globally aging population, exploring interventions that counteract age-related cognitive decline and cerebral structural alterations is paramount. Among various strategies, physical exercise (PE) emerges as a prevalent activity routinely incorporated in many individuals' lives. This systematic review and meta-analysis aims to elucidate the impact of PE on white matter (WM) integrity and cognitive function in older adults. Data from 581 participants, 312 in the PE intervention group, and 269 in the control group were extracted from nine randomized controlled trials (RCTs) retrieved from databases including PubMed, Embase, Web of Science, and the Cochrane Library. The results indicated a significant improvement in white matter (WM) integrity in individuals engaged in PE, as evidenced by enhanced fractional anisotropy (FA) scores (SMD = 0.4, 95% confidence interval (CI) [0.05, 0.75], P = 0.024). The GRADE assessment revealed a moderate risk. However, no significant associations were found between PE and other metrics such as radial diffusivity (RD), mean diffusivity (MD), white matter volume (WMV), hippocampal volume (HV), and cognitive functions (executive function [EF], memory, processing speed). In conclusion, our study emphasizes the potential neurostructural and cognitive functional benefits of physical exercise for the brain health of older adults.

Motor experience modulates neural processing of lexical action language: Evidence from rugby players.

The perceptual symbol theory proposes a sensorimotor simulation in language processing, emphasizing the role of motor experience. However, the neural basis of motor experience on lexical-level language processing remains little known. In the current fMRI study, we compared brain activation and task-based functional connectivity in 28 rugby players and 28 novices during rugby- specialized and daily verb processing. Distinct differences were observed between the two groups in the bilateral superior temporal gyrus and left angular gyrus regions during specialized verb processing. Notably, intergroup functional connectivity was evident between the left superior temporal gyrus and the right precentral gyrus during specialized verb processing. This study contributes insights into the neural responses and connectivity patterns associated with motor experience at the lexical level, highlighting its potential impact on language processing.

Influence of conflicting prior information on action anticipation in soccer players: an ERP study.

Objective: Prior probability information and visual kinematic information are essential for action anticipation in athletes. The aims of this study were to examine how conflicting prior information influences anticipatory judgment in athletes vs. non-athletes and to explore the underlying cognitive mechanisms. Methods: The aim of Experiment 1 was to determine the moment when prior information influenced action anticipation in athletes vs. non-athletes. To that end, 17 semi-elite soccer goalkeepers and 18 non-athletes received prior information about the probability of the direction that a player on a video would kick a ball into the goal. Participants then anticipated the trajectory of the ball when the action of the player's kick on the video was truncated at the moment the foot contacted the ball (time T) or one frame (T-1; 50 ms) or two frames (T-2; 100 ms) before the foot-ball contact. The aim of Experiment 2 was to elucidate the adaptive cognitive-motor behavior exhibited by highly trained soccer players at the moment when their anticipatory performance was most influenced by prior information. Experiment 2 included 27 different semi-elite soccer players with many years of experience as a goalkeeper and 27 different non-athletes. Participants anticipated the direction of the kick when the kinematic action of the kicker at the moment the anticipatory performance of the participants was most influenced by prior information (as determined in Experiment 1) was congruent, incongruent, or neutral. Action anticipation accuracy and response time were evaluated for both experiments, whereas event-related potential components N1, N2, and P3 were assessed only in Experiment 2. Results: The results of Experiment 1 showed that anticipatory accuracy was significantly higher among athletes than non-athletes and that anticipatory accuracy with directional information given was significantly higher than that when no prior information was given or when prior information without directional information was given (p < 0.001) for both T-1 (p's ≤ 0.034) and T-2 (p's < 0.001) occlusion points. In Experiment 2 using those two video occlusion times, the amplitude of the N1 component, which reflects selective attention to stimulus properties, was significantly higher in athletes than in non-athletes (p < 0.001). The amplitude of the N2 component, which has been associated with conflict monitoring, for the incongruent condition was significantly higher than that for both neutral (p < 0.001) and congruent (p < 0.001) conditions in athletes. Non-athletes exhibited no significant N2 amplitude differences for any prior information condition. Conclusion: Integrating prior information enhanced action anticipation in semi-elite soccer players, particularly 50 and 100 ms before the foot-ball contact. Semi-elite soccer players prioritized early selective attention and conflict monitoring of kinematic information, facilitating action anticipation using the prior information.

Enzyme-catalyzed electrochemical aptasensor for ultrasensitive detection of soluble PD-L1 in breast cancer based on decorated covalent organic frameworks and carbon nanotubes.

BACKGROUND: Soluble programmed death-ligand 1 (sPD-L1) is critically involved in breast cancer recurrence and metastasis. However, the clinical application of highly sensitive sPD-L1 assays remains a challenge due to its low abundance in peripheral blood. To address this issue, for the first time, an enzyme-catalyzed electrochemical aptasensing platform was devised, incorporating covalent organic frameworks-gold nanoparticles-antibody-horseradish peroxidase (COFs-AuNPs-Ab-HRP) and polyethyleneimine-functionalized multiwalled carbon nanotubes (MWCNTs-PEI-AuNPs) for the highly specific and ultrasensitive detection of sPD-L1. RESULTS: MWCNTs-PEI-AuNPs possessed an extensive specific surface area and exhibited excellent electrical conductivity, facilitating the immobilization of aptamer and amplifying the signal. COFs modified with AuNPs not only amplified the electrical signal but also proffered a loading platform for the Ab and HRP. The favorable biocompatibility of COFs contributed to the preservation of enzyme activity and stability. HRP acted in synergy with hydrogen peroxide (H2O2) to catalyze the oxidation of hydroquinone (HQ) to benzoquinone (BQ). Subsequently, BQ underwent electrochemical reduction to HQ, inducing an enzymatic redox cycle that amplified the electrochemical signal and enhanced the sensitivity and selectivity of the detection method. The developed aptasensor displayed a liner range for sPD-L1 identification from 1 pg mL-1 to 100 ng mL-1 and the detection limit reached 0.143 pg mL-1 (S/N = 3). SIGNIFICANCE: Paving the way for clinical application, this strategy detected differences in sPD-L1 in cell supernatants and peripheral blood of breast cancer patients with higher sensitivity compared to commercial sPD-L1 ELISA kit. This work demonstrates significant potential in offering reference information for early diagnosis and disease surveillance of breast cancer.

Blood virome of patients with traumatic sepsis.

Sepsis is one of the possible outcomes of severe trauma, and it poses a dire threat to human life, particularly in immunocompromised people. The most prevalent pathogens are bacteria and fungi, but viruses should not be overlooked. For viral metagenomic analysis, we collected blood samples from eight patients with post-traumatic sepsis before and seven days after treatment. The results demonstrated that Anellovirus predominated the viral community, followed by Siphoviridae and Myoviridae, and that the variations in viral community and viral load before and after treatment were not statistically significant. This study allows us to investigate methods for establishing NGS-based viral diagnostic instruments for detecting viral infections in the blood of sepsis patients so that antiviral therapy can be administered quickly.

SARS-CoV-2 Nsp15 suppresses type I interferon production by inhibiting IRF3 phosphorylation and nuclear translocation.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes 2019 coronavirus disease (COVID-19), poses a significant threat to global public health security. Like other coronaviruses, SARS-CoV-2 has developed various strategies to inhibit the production of interferon (IFN). Here, we have discovered that SARS-CoV-2 Nsp15 obviously reduces the expression of IFN-ß and IFN-stimulated genes (ISG56, CXCL10), and also inhibits IRF3 phosphorylation and nuclear translocation by antagonizing the RLR-mediated antiviral signaling pathway. Mechanically, we found that the poly-U-specific endonuclease domain (EndoU) of Nsp15 directly associates with the kinase domain (KD) of TBK1 to interfere TBK1 interacting with IRF3 and the flowing TBK1-mediated IRF3 phosphorylation. Furthermore, Nsp15 also prevented nuclear translocation of phosphorylated IRF3 via binding to the nuclear import adaptor karyopherin α1 (KPNA1) and promoting it autophagy-dependent degradation. These findings collectively reveal a novel mechanism by which Nsp15 antagonizes host's innate immune response.

Viral metagenomics of the gut virome of diarrheal children with Rotavirus A infection.

Diarrhea is a leading cause of morbidity and mortality in children worldwide and represents a major dysbiosis event. Rotavirus has been recognized as a global leading pathogen of diarrhea. This study is aimed at investigating differences in the gut virome between diarrheal children and healthy controls. In 2018, 76 diarrheal fecal samples and 27 healthy fecal samples in Shanghai and 40 diarrheal fecal samples and 19 healthy fecal samples in Taizhou were collected to investigate the composition of the gut virome. Viral metagenomic analyses revealed that the alpha diversity of the diarrheal virome was not significantly different from that of the healthy virome, and the beta diversity had a significant difference between diarrheal and healthy children. The diarrheal virome was mainly dominated by the families Adenoviridae, Astroviridae, Caliciviridae, and Picornaviridae. Meanwhile, the healthy virome also contains phages, including Microviridae and Caudovirales. The high prevalence of diverse enteric viruses in all samples and the little abundance of Microviridae and Caudovirales in diarrheal groups were identified. The study introduced a general overview of the gut virome in diarrheal children, revealed the compositional differences in the gut viral community compared to healthy controls, and provided a reference for efficient treatments and prevention of virus-infectious diarrhea in children.

Gastric cancer mesenchymal stem cells via the CXCR2/HK2/PD-L1 pathway mediate immunosuppression.

BACKGROUND: Anti-PD-1 immunotherapy has emerged as an important therapeutic modality in advanced gastric cancer (GC). However, drug resistance frequently develops, limiting its effectiveness. METHODS: The role of gastric cancer mesenchymal stem cells (GCMSCs) in anti-PD-1 resistance was evaluated in vivo in NPGCD34+ or NCGPBMC xenograft mouse model. In addition, we investigated CD8+T cell infiltration and effector function by spectral cytometry and IHC. The effects of GCMSCs conditional medium (GCMSC-CM) on GC cell lines were characterized at the level of the proteome, secretome using western blot, and ELISA assays. RESULTS: We reported that GCMSCs mediated tolerance mechanisms contribute to tumor immunotherapy tolerance. GCMSC-CM attenuated the antitumor activity of PD-1 antibody and inhibited immune response in humanized mouse model. In GC cells under serum deprivation and hypoxia, GCMSC-CM promoted GC cells proliferation via upregulating PD-L1 expression. Mechanistically, GCMSC-derived IL-8 and AKT-mediated phosphorylation facilitated HK2 nuclear localization. Phosphorylated-HK2 promoted PD-L1 transcription by binding to HIF-1α. What is more, GCMSC-CM also induced lactate overproduction in GC cells in vitro and xenograft tumors in vivo, leading to impaired function of CD8+ T cells. Furthermore, CXCR1/2 receptor depletion, CXCR2 receptor antagonist AZD5069 and IL-8 neutralizing antibody application also significantly reversed GCMSCs mediated immunosuppression, restoring the antitumor capacity of PD-1 antibody. CONCLUSIONS: Our findings reveal that blocking GCMSCs-derived IL-8/CXCR2 pathway decreasing PD-L1 expression and lactate production, improving antitumor efficacy of anti-PD-1 immunotherapy, may be of value for the treatment of advanced gastric carcinoma.

GC­MSC­derived circ_0024107 promotes gastric cancer cell lymphatic metastasis via fatty acid oxidation metabolic reprogramming mediated by the miR­5572/6855­5p/CPT1A axis.

Gastric cancer tissue­derived mesenchymal stem cells (GC­MSCs) play a critical role in facilitating gastric cancer metastasis. Recently, circular RNAs (circRNAs) and metabolic reprogramming have been found to be extensively involved in the malignant progression of tumors, including gastric cancer. However, the biological role and potential mechanisms of GC­MSC­derived circRNAs in metabolic reprogramming remain elusive. Herein, the expression profiles of circRNAs and mRNAs were compared between GC­MSCs and bone marrow­derived MSCs (BM­MSCs) using microarray analysis. circ_0024107 was identified to mediate GC­MSCs to promote gastric cancer lymphatic metastasis by inducing fatty acid oxidation (FAO) metabolic reprogramming. Mechanistically, circ_0024107 served as a sponge of miR­5572 and miR­6855­5p to elicit the FAO metabolic reprograming of GC­MSCs by upregulating carnitine palmitoyltransferase 1A (CPT1A). In addition, GC­MSCs promoted metastasis which was dependent on the induction of FAO in gastric cancer cells mediated by circ_0024107. The circ_0024107/miR­5572/6855­5p/CPT1A axis was deregulated in gastric cancer tissues and GC­MSCs, and was associated with lymph node metastasis and the prognosis of patients with gastric cancer. Taken together, the findings of the present study suggest the crucial role of FAO metabolic reprogramming mediated by GC­MSC­derived circ_0024107 in synergistically promoting gastric cancer lymphatic metastasis via miR­5572/6855­5p­CPT1A signaling; this suggests that circ_0024107 may be an attractive target for gastric cancer intervention.

Hsa_circ_0073453 modulates IL-8 secretion by GC-MSCs to promote gastric cancer progression by sponging miR-146a-5p.

Gastric cancer associated mesenchymal stem cells (GC-MSCs) have been demonstrated to promote gastric cancer progression in a paracrine manner. IL-8 is highly secreted by GC-MSCs and is crucial for their oncogenic function. However, the mechanism underlying the modulation of IL-8 secretion by GC-MSCs has not been well elucidated. In this study, Shbio-human ceRNA array was used to identify dysregulated mRNAs and circRNAs between GC-MSCs and bone marrow derived mesenchymal stem cells (BM-MSCs). IL-8 was validated to be a critical paracrine cytokine for GC-MSCs promoting migration and invasion of gastric cancer cells. circ_0073453 was identified as a novel GC-MSC-derived circRNA which acted as a sponge of miR-146a-5p, thus increasing IL-8 expression and secretion to promote gastric cancer cell metastasis. Furthermore, circ_0073453 modulated IL-8 secretion by GC-MSCs to enhance gastric cancer cells PD-L1 expression to resist cytotoxic CD8+ T cell-killing. circ_0073453/miR-146a-5p/IL-8 axis was deregulated in gastric cancer tissues and associated with prognosis depending on MSC abundance in cancer tissues. Taken together, our findings suggest that circ_0073453/miR-146a-5p/IL-8 axis is critical for GC-MSCs promoting gastric cancer progression. Hence, hsa_circ_0073453 may be a potential therapeutic target for gastric cancer.