Opioid use disorder (OUD) is a medical condition that is effectively treated with medications. A major challenge in breaking the cycle of OUD and related illegal activity is seamlessly introducing medications for opioid use disorder (MOUD) as individuals leave jail or prison. We examined the feasibility of a pilot intervention to link participants to ongoing MOUD and psychosocial supports following release from custody.

Stunting is one of the most public health burdens in Rwanda. Most deaths due to stunting are associated with inappropriate feeding practices that occur in the first 5 years of life. This study aimed at determining the risk factors for stunting in children under 5 years of age in the Eastern and Western provinces of Rwanda.

The growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis plays an important role in brain structure and maintenance of brain function. There is a close correlation between serum GH and IGF1 levels and age-related cognitive function. The effects of childhood-onset growth hormone deficiency (GHD)on brain morphology are underestimated so far.

Amyotrophic lateral sclerosis (ALS) arises from an interplay of genetic mutations and environmental factors. ssRNA viruses are possible ALS risk factors, but testing their interaction with mutations such as in FUS, which encodes an RNA-binding protein, has been difficult due to the lack of a human disease model. Here, we use isogenic induced pluripotent stem cell (iPSC)-derived spinal neurons (SNs) to investigate the interaction between ssRNA viruses and mutant FUS. We find that rabies virus (RABV) spreads ALS phenotypes, including the formation of stress granules (SGs) with aberrant composition due to increased levels of FUS protein, as well as neurodegeneration and reduced restriction activity by FUS mutations. Consistent with this, iPSC-derived SNs harboring mutant FUS are more sensitive to human immunodeficiency virus (HIV-1) and Zika viruses (ZIKV). We demonstrate that RABV and HIV-1 exacerbate cytoplasmic mislocalization of FUS. Our results demonstrate that viral infections worsen ALS pathology in SNs with genetic risk factors, suggesting a novel role for viruses in modulating patient phenotypes.

Neuroinflammation is one of the important factors aggravating brain injury after ischemic stroke. We aimed to investigate the effects of cerebrolysin (CBL) on neuroinflammation in vivo and in vitro and the underlying mechanisms. The gene expressions of pro-inflammatory factors and anti-inflammatory factors were analyzed by real time PCR in rat transient middle cerebral artery occlusion (tMCAO) model, lipopolysaccharides-induced neuroinflammatory mice model and LPS-treated mouse primary microglia cells. The neuroprotective effects of CBL were evaluated by infarct size, Longa test and Rotarod test for long-term functional recovery in rats subjected to ischemia. The role of CREB/PGC-1α pathway in anti-neuroinflammatory effect of CBL was also determined by real time PCR and Western blotting. In the tMCAO model, administration of CBL at 3 h post-ischemia reduced infarct volume, promoted long-term functional recovery, decreased the gene expression of pro-inflammatory factors and increased the gene expression of anti-inflammatory factors. Correspondingly, in LPS-induced neuroinflammatory mice model, CBL treatment attenuated sickness behavior, decreased the gene expression of pro-inflammatory factors, and increased the gene expression of anti-inflammatory factors. In in vitro and in vivo experiments, CBL increased the protein expression levels of PGC-1α and phosphorylated CREB to play anti-inflammatory effect. Additionally, the application of the specific CREB inhibitor, 666-15 compound could effectively reverse the anti-inflammatory effect of CBL in primary mouse microglia cells and anti-ischemic brain injury of CBL in rats subjected to tMCAO. In conclusion, CBL ameliorated cerebral ischemia injury through reducing neuroinflammation partly via the activation of CREB/PGC-1α pathway and may play a therapeutic role as anti-neuroinflammatory agents in the brain disorders associated with neuroinflammation.

Global cerebral ischemia (GCI) commonly occurs in the elderly. Subcortical white matter lesions and oligodendrocyte (OLG) loss caused by cerebral ischemia have been implicated in the development of post-ischemic depression and cognitive impairment. OLGs are necessary for axonal myelination; the disrupted differentiation of OLG progenitor cells (OPCs) is associated with impaired remyelination. Evidence has indicated that increased levels of inflammatory cytokines released from activated microglia induce depression-like behaviors by affecting neurotransmitter pathways, but the mechanisms remain elusive. We explored the potential mechanisms that link microglia activation with GCI-induced depression and cognitive dysfunction by studying effects of minocycline on white matter damage, cytokine levels, and the monoaminergic neurotransmitters. An acute GCI animal model was generated through bilateral common carotid artery occlusion to induce ischemic inflammation and subcortical white matter damage. Minocycline, an inhibitor of microglia activation, was intraperitoneally administrated immediately after surgery and continued daily for additional six days. Minocycline shortened the immobile duration in tail suspension test and forced swimming test, while no improvement was found in Morris water maze test. The plasma levels of IL-1β, IL-6, TNF-α, HMGB1, and netrin-1 were significantly reduced with the treatment of minocycline. Minocycline treatment substantially reversed demyelination in corpus callosum and hippocampus, alleviated hippocampal microglia activation, and promoted OPCs maturation, while no effect was found on hippocampal neurodegeneration. Besides, the content of dopamine (DA) in the hippocampus was upregulated by minocycline treatment after GCI. Collectively, our data demonstrated that minocycline exerts an anti-depressant effect by inhibiting microglia activation, promoting OPCs maturation and remyelination. Increased DA in hippocampus may also play a role in ameliorating depressive behavior with minocycline treatment.

As for traditional Chinese medicine (TCM) prescription, what puzzled researchers most was how to select proper chemical markers to represent the whole pharmacological action system. In this paper, an integrated metabolomic method was presented for a systematic discovery of potential active components in Fangji Huangqi Tang (FHT), a well-known TCM prescription for nephrotic syndrome treatment, based on "correlations between chemical and metabolic profiles." Firstly, a metabolomics study was carried out to select representative biomarkers of nephrotic syndrome. Then, after drug administration, the dynamic process of serum composition was investigated by the ultra-high performance liquid chromatography coupled with electrospray ionization-quadrupole-time of flight-mass spectrometry (UHPLC-ESI-Q-TOF-MS) technique to detect the prototypes and related metabolites of relative components from FHT. Pearson correlation analysis was finally used to find out the correlations between the endogenous metabolic spectrums and the chemical serum spectrums. As a result, 17 biomarkers for nephrotic syndrome indication were identified, and the main metabolic pathways of their concern included linoleic acid metabolism; cyanoamino acid metabolism; alpha-linolenic acid metabolism; glycine, serine, and threonine metabolism; arachidonic acid metabolism; and glycerophospholipid metabolism. Meanwhile, active components in FHT for nephrotic syndrome treatment were screened out, including (+)-tetrandrine demethylation, fenfangjine G hydrogenation, tetrandrine, N-methylfangchinoline, tetrandrine demethylation, fangchinoline, glycyrrhetic acid, astragaloside II alcohol dehydration, atractylenolide III demethylation + hydrogenation, atractylenolide III demethylation + hydrogenation, and licoricone-N-acetylcysteine conjugation. This study demonstrated a promising way to elucidate the active chemical material basis of TCM prescription.

Serotonin (5-HT) is a major neuromodulator acting on the nervous system. Its various effects have been studied in vertebrates, as well as in arthropods, from the cellular and subcellular compartments up to the behavioral level, which includes the control of mood, aggression, locomotion, and anxiety. The diversity of responses of neurons to 5-HT has been related to its mode of application, the diversity of 5-HT-receptors, and the animals' social status history. In the locomotor network of socially isolated crayfish, the duality of 5-HT-evoked responses (excitatory/inhibitory) on motoneurons (MNs), sensorimotor pathways, and their consequences on motor network activity has largely been studied. The aim of the present report is to examine if this duality of exogenous 5-HT-evoked responses in the crayfish locomotor network can be reproduced by direct activation of 5-HT neurons in the case of socially isolated animals. Our previous studies have focused on the mechanisms supporting these opposite effects on MNs, pointing out spatial segregation of 5-HT receptors responsible either for positive or negative responses. Here, we report new findings indicating that excitatory and inhibitory effects can be achieved simultaneously in different leg MNs by the activation of a single 5-HT cell in the first abdominal ganglion.

Hyperuricemia plays a critical causative role in gout. In contrast, hyperuricemia has a protective effect in neurodegenerative disorders, including Alzheimer's Disease. Genetic variation in the SLC2A9 gene, encoding the urate transporter GLUT9, exerts the largest single-gene effect on serum uric acid (SUA). We report here the identification of two GLUT9-interacting proteins, integral membrane protein 2B (ITM2B) and transmembrane protein 85 (TMEM85), isolated from a human kidney cDNA library using the dual-membrane yeast two-hybrid system. ITM2B is a ubiquitously expressed, N-glycosylated transmembrane regulatory protein, involved in familial dementias and retinal dystrophy; the function of TMEM85 is less defined. Using coimmunoprecipitation, we confirmed the physical interaction between ITM2B or TMEM85 and N-terminal GLUT9 isoforms (GLUT9a and GLUT9b) in transfected HEK 293T cells and Xenopus oocytes, wherein ITM2B but not TMEM85 inhibited GLUT9-mediated urate uptake. Additionally, co-expression of ITM2B with GLUT9 in oocytes inhibited N-glycosylation of GLUT9a more than GLUT9b and stimulated urate efflux by both isoforms. However, urate uptake by N-glycosylation and N-terminal deletion GLUT9 mutants was efficiently inhibited by ITM2B, indicating that neither N-glycosylation nor the N terminus is necessary for functional interaction of GLUT9 with ITM2B. Notably, ITM2B variants linked to familial Danish dementia and retinal dystrophy significantly attenuated the inhibition of GLUT9-mediated urate influx. We propose ITM2B as a potential regulatory link between urate homeostasis and neurodegenerative disorders.

The purpose of this work was to analyze the effects of a computerized training on attentional capacity in a group of young soccer players. Seventy-five male adolescents from two soccer clubs in the city of Malaga (Spain) and aged between 14 and 18 (15.45 ± 1.43 years) participated in the investigation. A quasi-experimental design was used, and the adolescents were divided into control (n = 38) and experimental (n = 37) groups. The experimental group underwent a computerized training (Rejilla 1.0) of their attention during 9 weeks and 27 sessions. In addition, the D2 attention test was used to analyze the evolution of participants after the intervention program. The results showed positive effects of the computerized intervention program on selective attention, observing changes both in the executions of the software used (p < 0.001, Cohen's d = 1.58, 95% CI [1.06, 2.11]) and in the main measures of the D2 test, total effectiveness (p < 0.001, Cohen's d = 0.62, 95% CI [0.15, 1.08]) and concentration (p < 0.01, Cohen's d = 0.48, 95% CI [0.02, 0.94]).

Inaccurate body size judgments are associated with body image disturbances, a clinical feature of many eating disorders. Accordingly, body-related stimuli have become increasingly important in the study of estimation inaccuracies and body image disturbances. Technological advancements in the last decade have led to an increased use of computer-generated (CG) body stimuli in body image research. However, recent face perception research has suggested that CG face stimuli are not recognized as readily and may not fully tap facial processing mechanisms. The current study assessed the effectiveness of using CG stimuli in an established body size estimation task (the "bodyline" task). Specifically, we examined whether employing CG body stimuli alters body size judgments and associated estimation biases. One hundred and six 17- to 25-year-old females completed the CG bodyline task, which involved estimating the size of full-length CG body stimuli along a visual analogue scale. Our results show that perception of body size for CG stimuli was non-linear. Participants struggled to discriminate between extreme bodies sizes and overestimated the size change between near to average bodies. Furthermore, one of our measured size estimation biases was larger for CG stimuli. Our collective findings suggest using caution when employing CG stimuli in experimental research on body perception.

Brucella abortus stimulates an inflammatory immune response that stimulates the endocrine system, inducing the secretion of dehydroepiandrosterone (DHEA) and cortisol. In humans, the active disease is generally present as osteoarticular brucellosis. In previous studies we showed that B. abortus infection of synoviocytes creates a proinflammatory microenvironment. We proposed to determine the role of cortisol and DHEA on synoviocytes and infiltrating monocytes during B. abortus infection. Cortisol inhibited IL-6, IL-8, MCP-1, and MMP-2 secretion induced by B. abortus infection in synovial fibroblast. Cortisol-mediated MMP-2 inhibition during B. abortus infection was reversed by IL-6. DHEA inhibited B. abortus-induced RANKL up-regulation in synovial fibroblast through estrogen receptor (ER). B. abortus infection did not modulate glucocorticoid receptor (GR) expression. Cell responses to cortisol also depended on its intracellular bioavailability, according to the activity of the isoenzymes 11β-hydroxysteroid dehydrogenase (HSD) type-1 and 11β-HSD2 (which are involved in cortisone-cortisol interconversion). B. abortus infection did not modify 11β-HSD1 expression and GRα/β ratio in the presence or absence of adrenal steroids. Supernatants from B. abortus-infected monocytes induced 11β-HSD1 in synovial cells. Administration of cortisone was capable of inhibiting the secretion of RANKL by synoviocytes mimicking cortisol's effect. These results go along with previous observations that highlighted the ability of synovial tissue to secrete active steroids, making it an intracrine tissue. This is the first study that contributes to the knowledge of the consequence of adrenal steroids on synoviocytes in the context of a bacterial infection.

Dairy product consumption is a common habit in Brazil. These products present a good matrix for probiotic incorporation. Thus, in this study the feasibility of producing a probiotic "requeijão cremoso" incorporated with Bacillus coagulans GBI-30 6086 in three different steps and its metabolic effect in an animal model for 2 weeks has been evaluated. Wistar adult health rats were randomized into one to five groups (n = 8 for each group): Control (C); "requeijão cremoso" without probiotic (RC); probiotic inoculated in the milk before pasteurization at 65°C/30 min (RPP); "requeijão cremoso" inoculated before the fusion step and consequently exposed to 90°C/5 min (RPF); and "requeijão cremoso" inoculated after fusion step, i.e., once the product temperature reached 50°C (RPAF). At the end of treatment, analysis of molecular markers of proteins of stress and antioxidant system, HSP 25, 60, 70 and 90, SOD and catalase were performed in the animals' muscles by Western Blot technique. The HSP25, HSP90 and catalase levels of C, RPP, RPF, and RPAF were similar, indicating that the homeostasis remained unchanged. The incorporation of B. coagulans GBI-30 6086 in the "requeijão cremoso" was shown to be stable and the microorganism remained viable in all steps tested. The incorporation of the probiotic strain in the fusion stage facilitated the technological process, since it allowed a better homogenization of the product and did not affect the maintenance of the metabolic homeostasis of rats.

Background: Ninety percent of systemic lupus erythematosus (SLE) patients are women. X chromosome-dosage increases susceptibility to SLE and primary Sjögren's syndrome (pSS). Chromosome X open reading frame 21 (CXorf21) escapes X-inactivation and is an SLE risk gene of previously unknown function. We undertook the present study to delineate the function of CXorf21 in the immune system as well as investigate a potential role in the sex bias of SLE and pSS. Methods: Western blot protein analysis, qPCR, BioPlex cytokine immunoassay, pHrodo™ assays, as well as in vitro CRISPR-Cas9 knockdown experiments were employed to delineate the role of CXorf21 in relevant immunocytes. Results: Expressed in monocytes and B cells, CXorf21 basal Mrna, and protein expression levels are elevated in female primary monocytes, B cells, and EBV-transformed B cells compared to male cells. We also found CXorf21 mRNA and protein expression is higher in both male and female cells from SLE patients compared to control subjects. TLR7 ligation increased CXorf21 protein expression and CXorf21 knockdown abrogated TLR7-driven increased IFNA1 mRNA expression, and reduced secretion of both TNF-alpha and IL-6 in healthy female monocytes. Similarly, we found increased pH in the lysosomes of CXorf21-deficient female monocytes. Conclusion: CXorf21 is more highly expressed in female compared to male cells and is involved in a sexually dimorphic response to TLR7 activation. In addition, CXorf21 expression regulates lysosomal pH in a sexually dimorphic manner. Thus, sexually dimorphic expression of CXorf21 skews cellular immune responses in manner consistent with expected properties of a mediator of the X chromosome dose risk in SLE and pSS.

The New World arenavirus Junin (JUNV) is the etiological agent of Argentine hemorrhagic fever (AHF). Previous studies of human macrophage infection by the Old-World arenaviruses Mopeia and Lassa showed that while the non-pathogenic Mopeia virus replicates and activates human macrophages, the pathogenic Lassa virus replicates but fails to activate human macrophages. Less is known in regard to the impact of New World arenavirus infection on the human macrophage immune response. Macrophage activation is critical for controlling infections but could also be usurped favoring immune evasion. Therefore, it is crucial to understand how the JUNV infection modulates macrophage plasticity to clarify its role in AHF pathogenesis. With this aim in mind, we compared infection with the attenuated Candid 1 (C#1) or the pathogenic P strains of the JUNV virus in human macrophage cultures. The results showed that both JUNV strains similarly replicated and induced morphological changes as early as 1 day post-infection. However, both strains differentially induced the expression of CD71, the receptor for cell entry, the activation and maturation molecules CD80, CD86, and HLA-DR and selectively modulated cytokine production. Higher levels of TNF-α, IL-10, and IL-12 were detected with C#1 strain, while the P strain induced only higher levels of IL-6. We also found that C#1 strain infection skewed macrophage polarization to M1, whereas the P strain shifted the response to an M2 phenotype. Interestingly, the MERTK receptor, that negatively regulates the immune response, was down-regulated by C#1 strain and up-regulated by P strain infection. Similarly, the target genes of MERTK activation, the cytokine suppressors SOCS1 and SOCS3, were also increased after P strain infection, in addition to IRF-1, that regulates type I IFN levels, which were higher with C#1 compared with P strain infection. Together, this differential activation/polarization pattern of macrophages elicited by P strain suggests a more evasive immune response and may have important implications in the pathogenesis of AHF and underpinning the development of new potential therapeutic strategies.

The lace plant (Aponogeton madagascariensis) is an aquatic monocot that utilizes programmed cell death (PCD) to form perforations throughout its mature leaves as part of normal development. The lace plant is an emerging model system representing a unique form of developmental PCD. The role of autophagy in lace plant PCD was investigated using live cell imaging, transmission electron microscopy (TEM), immunolocalization, and in vivo pharmacological experimentation. ATG8 immunostaining and acridine orange staining revealed that autophagy occurs in both healthy and dying cells. Autophagosome-like vesicles were also found in healthy and dying cells through ultrastructural analysis with TEM. Following autophagy modulation, there was a noticeable increase in vesicles and vacuolar aggregates. A novel cell death assay utilizing lace plant leaves revealed that autophagy enhancement with rapamycin significantly decreased cell death rates compared to the control, whereas inhibition of autophagosome formation with wortmannin or blocking the degradation of cargoes with concanamycin A had an opposite effect. Although autophagy modulation significantly affected cell death rates in cells that are destined to die, neither the promotion nor inhibition of autophagy in whole plants had a significant effect on the number of perforations formed in lace plant leaves. Our data indicate that autophagy predominantly contributes to cell survival, and we found no clear evidence for its direct involvement in the induction of developmental PCD during perforation formation in lace plant leaves.

Ataxia Telangiectasia and Rad-3-related protein (ATR) is a DNA damage signaling kinase required for the monitoring of DNA integrity. Together with ATM and SOG1, it is a key player in the transcriptional regulation of DNA damage response (DDR) genes in plants. In this study, we describe the role of ATR in the DDR pathway in barley and the function of the HvATR gene in response to DNA damages induced by aluminum toxicity. Aluminum is the third most abundant element in the Earth's crust. It becomes highly phytotoxic in acidic soils, which comprise more than 50% of arable lands worldwide. At low pH, Al is known to be a genotoxic agent causing DNA damage and cell cycle arrest. We present barley mutants, hvatr.g and hvatr.i, developed by TILLING strategy. The hvatr.g mutant carries a G6054A missense mutation in the ATR gene, leading to the substitution of a highly conserved amino acid in the protein (G1015S). The hvatr.g mutant showed the impaired DDR pathway. It accumulated DNA damages in the nuclei of root meristem cells when grown in control conditions. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) analysis revealed that 60% of mutant nuclei possessed DNA nicks and breaks, whereas in the wild type only 2% of the nuclei were TUNEL-positive. The high frequency of DNA damages did not lead to the inhibition of the cell cycle progression, but the mutant showed an increased number of cells in the G2/M phase. In response to treatments with different Al doses, hvatr.g showed a high level of tolerance. The retention of root growth, which is the most evident symptom of Al toxicity, was not observed in the mutant, as it was in its parent variety. Furthermore, Al treatment increased the level of DNA damages, but did not affect the mitotic activity and the cell cycle profile in the hvatr.g mutant. A similar phenotype was observed for the hvatr.i mutant, carrying another missense mutation leading to G903E substitution in the HvATR protein. Our results demonstrate that the impaired mechanism of DNA damage response may lead to aluminum tolerance. They shed a new light on the role of the ATR-dependent DDR pathway in an agronomically important species.

Traditional approaches to cancer therapy seek common molecular targets in tumors from different patients. However, molecular profiles differ between patients, and most tumors exhibit inherent heterogeneity. Hence, imprecise targeting commonly results in side effects, reduced efficacy, and drug resistance. By contrast, personalized medicine aims to establish a molecular diagnosis specific to each patient, which is currently feasible due to the progress achieved with high-throughput technologies. In this report, we explored data from human RNA-seq and protein-protein interaction (PPI) networks using bioinformatics to investigate the relationship between tumor entropy and aggressiveness. To compare PPI subnetworks of different sizes, we calculated the Shannon entropy associated with vertex connections of differentially expressed genes comparing tumor samples with their paired control tissues. We found that the inhibition of up-regulated connectivity hubs led to a higher reduction of subnetwork entropy compared to that obtained with the inhibition of targets selected at random. Furthermore, these hubs were described to be participating in tumor processes. We also found a significant negative correlation between subnetwork entropies of tumors and the respective 5-year survival rates of the corresponding cancer types. This correlation was also observed considering patients with lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) based on the clinical data from The Cancer Genome Atlas database (TCGA). Thus, network entropy increases in parallel with tumor aggressiveness but does not correlate with PPI subnetwork size. This correlation is consistent with previous reports and allowed us to assess the number of hubs to be inhibited for therapy to be effective, in the context of precision medicine, by reference to the 100% patient survival rate 5 years after diagnosis. Large standard deviations of subnetwork entropies and variations in target numbers per patient among tumor types characterize tumor heterogeneity.

Automated phenotyping technologies are continually advancing the breeding process. However, collecting various secondary traits throughout the growing season and processing massive amounts of data still take great efforts and time. Selecting a minimum number of secondary traits that have the maximum predictive power has the potential to reduce phenotyping efforts. The objective of this study was to select principal features extracted from UAV imagery and critical growth stages that contributed the most in explaining winter wheat grain yield. Five dates of multispectral images and seven dates of RGB images were collected by a UAV system during the spring growing season in 2018. Two classes of features (variables), totaling to 172 variables, were extracted for each plot from the vegetation index and plant height maps, including pixel statistics and dynamic growth rates. A parametric algorithm, LASSO regression (the least angle and shrinkage selection operator), and a non-parametric algorithm, random forest, were applied for variable selection. The regression coefficients estimated by LASSO and the permutation importance scores provided by random forest were used to determine the ten most important variables influencing grain yield from each algorithm.

Rationale The small molecule Kartogenin (KGN) promotes cartilage regeneration in osteoarthritis (OA) by activating stem cells differentiation, but its pharmacological mode-of-action remains unclear. KGN can be cleaved into 4-aminobiphenyl (4-ABP) and phthalic acid (PA) following enzymolysis of an amide bond. Therefore, this study investigated whether 4-ABP or PA exerted the same action as KGN. Methods KGN, 4-ABP and PA were analyzed in cartilage of mice after oral, intravenous or intra-articular administration of KGN by liquid chromatography-mass spectrometry method. Their effect on proliferation and chondrogenic differentiation of mesenchymal stem cells (MSC) was evaluated in vitro. Furthermore, their effect on cartilage preservation was tested in mice OA model induced by destabilization of medial meniscus. OA severity was quantified using OARSI histological scoring. Transcriptional analysis was used to find the possible targets of the chemicals, which were further validated. Results We demonstrated that while oral or intra-articular KGN delivery effectively ameliorated OA phenotypes in mice, only 4-ABP was detectable in cartilage. 4-ABP could induce chondrogenic differentiation and proliferation of MSC in vitro and promote cartilage repair in OA mouse models mainly by increasing the number of CD44+/CD105+ stem-cell and prevention of matrix loss. These effect of 4-ABP was stronger than that of KGN. Transcriptional profiling of 4-ABP-stimulated MSC suggested that RPS6KA2 and the PI3K-Akt pathway were 4-ABP targets; 4-ABP could activate the PI3K-Akt pathway to promote MSC proliferation and repair OA injury, which was blocked in RPS6KA2-knockdown MSC or RPS6KA2-deficient mice.Conclusion 4-ABP bio-distribution in cartilage promotes proliferation and chondrogenic differentiation of MSC, and repairs osteoarthritic lesions via PI3K-Akt pathway activation.