Remodeling ceramide homeostasis promotes functional maturation of human pluripotent stem cell-derived ß cells.

Human pluripotent stem cell-derived ß cells (hPSC-ß cells) show the potential to restore euglycemia. However, the immature functionality of hPSC-ß cells has limited their efficacy in application. Here, by deciphering the continuous maturation process of hPSC-ß cells post transplantation via single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq), we show that functional maturation of hPSC-ß cells is an orderly multistep process during which cells sequentially undergo metabolic adaption, removal of negative regulators of cell function, and establishment of a more specialized transcriptome and epigenome. Importantly, remodeling lipid metabolism, especially downregulating the metabolic activity of ceramides, the central hub of sphingolipid metabolism, is critical for ß cell maturation. Limiting intracellular accumulation of ceramides in hPSC-ß cells remarkably enhanced their function, as indicated by improvements in insulin processing and glucose-stimulated insulin secretion. In summary, our findings provide insights into the maturation of human pancreatic ß cells and highlight the importance of ceramide homeostasis in function acquisition.

Exploration of TCM syndrome types of the material basis and risk prediction of Wilson disease liver fibrosis based on 1H NMR metabolomics.

Wilson disease (WD) is an autosomal recessive disorder characterized by abnormal copper metabolism. The accumulation of copper in the liver can progress to liver fibrosis and, ultimately, cirrhosis, which is a primary cause of death in WD patients. Metabonomic technology offers an effective approach to investigate the traditional Chinese medicine (TCM) syndrome types of WD-related liver fibrosis by monitoring the alterations in small molecule metabolites within the body. In this study, we employed 1H-Nuclear Magnetic Resonance (1H NMR) metabonomics to assess the metabolic profiles associated with five TCM syndrome types of WD-related liver fibrosis and analyzed the diagnostic and predictive capabilities of various metabolites. The study found a variety of metabolites, each with varying levels of diagnostic and predictive capabilities. Furthermore, the discerned differential metabolic pathways were primarily associated with various pathways involving carbohydrate metabolism, amino acid metabolism, and lipid metabolism. This study has identified various characteristic metabolic markers and pathways associated with different TCM syndromes of liver fibrosis in WD, providing a substantial foundation for investigating the mechanisms underlying these TCM syndromes.

BET inhibition induces synthetic lethality in PTEN deficient colorectal cancers via dual action on p21CIP1/WAF1.

Loss of PTEN tumor suppressor is an important event during colorectal cancer (CRC) development and is a target for therapeutic exploitation. This study reports that bromodomain and extra-terminal motif (BET) is a synthetic lethal partner of PTEN in CRC. BET inhibition (BETi) selectively induced G1 cell cycle arrest and apoptosis in PTEN-/- CRC. Further, BETi selectively and dose-dependently suppressed the growth of PTEN-/- CRC tumor xenografts in mice and patient-derived organoids. Mechanistically, PTEN-deficient CRC cells elevated the level of cytoplasmic p21CIP1/WAF1 that is hyper-phosphorylated at Thr145 by AKT. BETi suppressed AKT activation in PTEN-deficient CRC cells, followed by the reduction in p21 phosphorylation at Thr145, thereby promoting its nuclear translocation. In addition, BETi suppressed MYC level and this in turn increased the total p21 level in the nuclei. Over-expression of a phospho-mimetic p21 mutant (T145D) significantly rescued the BETi effect on PTEN-deficient CRC. These results suggest that BETi has a dual action on p21: elevating the level of p21 by inhibiting MYC and converting the oncogenic (cytoplasmic) p21 into the tumor-suppressive (nuclear) p21 by inhibiting AKT. Taken together, this study identified the synthetic lethal interaction between PTEN and BET, and provides a potential actionable target for CRC with PTEN loss.

[Focusing on the major national demands and developing novel research models--the research progress and prospective of islet organoid].

Diabetes is a major metabolic disease and health issue worldwide that imposes a heavy burden. Research on its pathogenesis and development of effective treatments are currently our major national demands. With the advent of organoid technology, islet organoids have emerged and are attracting increasing attention as a promising model for diabetes research. The establishment of islet organoids is based on the current understanding of islet development. With addition of extra induction factors in vitro to programmatically activate or inhibit specific signaling pathways during islet development, stem cells can be induced to differentiate into three-dimensional cell cultures that possess structures and functions similar to those of natural islets. Because of their capability to mimic the development of islets in vitro, faithfully replicate islet structure, and perform islet physiological functions, islet organoids have been widely used as a valuable tool for the investigation of diabetes pathogenesis, drug screening and evaluation, and clinical transplantation, showing a great potential application. This paper reviews the current research progress, application, and challenges of islet organoids, and discusses the future directions for research on islet organoids.

Palladium-catalysed aryl/monofluoroalkylation of allenamides: access to fluoroalkyl indoles and isoquinolones.

A palladium catalysed construction of fluoroalkyl indoles and isoquinolones through aryl/monofluoroalkylation of allenamides has been developed. Monofluoromethyl-substituted heterocycles could be accessed under mild conditions with broad functional group tolerance. In addition, indole-oxindole bisheterocyclic scaffolds bearing a fluorine atom were successfully synthesized with 3-fluoro-oxindole as the nucleophile by applying this method.

Association between the haemoglobin glycation index (HGI) and clinical outcomes in patients with acute decompensated heart failure.

BACKGROUND: A growing number of studies show that people with similar blood glucose levels have different levels of glycosylated haemoglobin (HbA1c), and relying only on HbA1c may lead to clinical decision-making errors. The haemoglobin glycation index (HGI) quantifies the difference in HbA1c among individuals and is strongly linked to the risk of cardiovascular disease. However, the connection between this phenomenon and the poor outcomes of patients with acute decompensated heart failure (ADHF) is currently unknown. PATIENTS AND METHODS: This retrospective, single-centre-based cohort study included 1531 hospitalized patients with ADHF from September 2010 to January 2020. The HGI is calculated from the difference between the observed and predicted HbA1c values [predicted HbA1c = 0.024 × fasting plasma glucose (FPG) (mg/dL)+3.1]. The endpoints examined in the study included all-cause death, cardiovascular (CV) death, and major adverse cardiac events (MACE). We fitted multivariable-adjusted Cox proportional hazard models to investigate the association between the HGI and clinical outcomes. RESULTS: During the five-year follow-up, 427 (27.9%) patients died from all causes, 232 (15.6%) from CV death, and 848 (55.4%) from MACE. The restricted cubic spline analysis also showed that the cumulative risk of all-cause and CV deaths decreased linearly with increasing HGI. According to multivariate Cox proportional hazard models, the highest tertile of the HGI was associated with a lower incidence of all-cause and cardiovascular deaths [all-cause death, adjusted hazard ratio (HR): 0.720, 95% confidence interval (CI): 0.563-0.921, p = 0.009; CV death, adjusted HR: 0.619, 95% CI: 0.445-0.861, p = 0.004]. A 1% increase in the HGI was associated with a 12.5% reduction in the risk of all-cause death and a 20.8% reduction in the risk of CV death. CONCLUSIONS: A high HGI was directly associated with a reduction in all-cause and CV deaths but was not associated with MACE. These findings may be helpful in the management of patients with ADHF.

Recent studies have demonstrated that significant discrepancies between HbA1c and actual blood glucose levels may lead to clinical decision-making errors.The inconsistency of previous research results suggests that the HGI may have different predictive ability in populations with different diseases.

Three-Component Synthesis of Multiple Functionalized Allenes via Copper/Photoredox Dual Catalyzed 1,4-Alkylcyanation of 1,3-Enynes.

Efficient access to multiple functionalized allenes via a three component 1,4-alkylcyanation of enynes with cyclic alcohol derivatives in the presence of trimethylsilyl cyanide (TMSCN) under copper/photoredox dual catalysis has been developed. Both easily transformable aldehyde and cyano groups were introduced to tetra-substituted allenes through light-induced C-C bond cleavage of cyclic butanol and pentanol derivatives. The reactions proceeded smoothly under mild conditions with broad functional groups tolerance.

Electrophile-Controlled Regiodivergent Palladium-Catalyzed Imidoylative Spirocyclization of Cyclic Alkenes.

An intermolecular controllable Pd-catalyzed spirocyclization of isocyano cycloalkenes has been developed, offering efficient and selective approaches toward spirocyclic hydropyrrole scaffolds. 2-Azaspiro-1,7-dienes could be obtained through a "chain-walking" process with aryl/vinyl iodides as electrophiles, while the normal Heck product 2-azaspiro-1,6-dienes were selectively generated when aryl triflates were used as the coupling partner of isocyanides. Mechanistic studies suggested that the counteranion of the Pd(II) intermediate played a crucial role in the regioselectivity control. Dihydropyrrole-fused 5,6,7-membered spirocycles were switchably accessed under mild conditions with wide functional group tolerance.

Upregulation of a Small-World Brain Network Improves Inhibitory Control: An fNIRS Neurofeedback Training Study.

The aim of this study was to investigate the inner link between the small-world brain network and inhibitory control. Functional near-infrared spectroscopy (fNIRS) was used to construct a neurofeedback (NF) training system and regulate the frontal small-world brain network. The small-world network downregulation group (DOWN, n = 17) and the small-world network upregulation group (UP, n = 17) received five days of fNIRS-NF training and performed the color-word Stroop task before and after training. The behavioral and functional brain network topology results of both groups were analyzed by a repeated-measures analysis of variance (ANOVA), which showed that the upregulation training helped to improve inhibitory control. The upregulated small-world brain network exhibits an increase in the brain network regularization, links widely dispersed brain resources, and reduces the lateralization of brain functional networks between hemispheres. This suggests an inherent correlation between small-world functional brain networks and inhibitory control; moreover, dynamic optimization under cost efficiency trade-offs provides a neural basis for inhibitory control. Inhibitory control is not a simple function of a single brain region or connectivity but rather an emergent property of a broader network.

Estimating residual undifferentiated cells in human chemically induced pluripotent stem cell derived islets using lncRNA as biomarkers.

Human pluripotent stem cells (hPSCs) can generate insulin-producing beta cells for diabetes treatment, but residual undifferentiated cells may cause tumors. We developed a highly sensitive assay to detect these cells in islet cells derived from human chemically induced pluripotent stem cells (hCiPSCs), which are transgene-free and safer. We used RNA-seq data to find protein-coding and non-coding RNAs that were only expressed in hCiPSCs, not in islet cells. We confirmed these biomarkers by RT-qPCR and ddPCR. We chose long non-coding RNA (lncRNA) markers, which performed better than protein-coding RNA markers. We found that LNCPRESS2, LINC00678 and LOC105370482 could detect 1, 1 and 3 hCiPSCs in 106 islet cells by ddPCR, respectively. We tested our method on several hCiPSC lines, which could quantify 0.0001% undifferentiated cell in 106 islet cells by targeting hCiPSCs-specific lncRNA transcripts, ensuring the safety and quality of hCiPSC-derived islet cells for clinical use.

ER translocon inhibitor ipomoeassin F inhibits triple-negative breast cancer growth via blocking ER molecular chaperones.

Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer where no effective therapy has been developed. Here, we report that the natural product ER translocon inhibitor ipomoeassin F is a selective inhibitor of TNBC cell growth. A proteomic analysis of TNBC cells revealed that ipomoeassin F significantly reduced the levels of ER molecular chaperones, including PDIA6 and PDIA4, and induced ER stress, unfolded protein response (UPR) and autophagy in TNBC cells. Mechanistically, ipomoeassin F, as an inhibitor of Sec61α-containing ER translocon, blocks ER translocation of PDIA6, inducing its proteasomal degradation. Silencing of PDIA6 or PDIA4 by RNA interferences or treatment with a small molecule inhibitor of the protein disulfide isomerases in TNBC cells successfully recapitulated the ipomoeassin F phenotypes, including the induction of ER stress, UPR and autophagy, suggesting that the reduction of PDIAs is the key mediator of the pharmacological effects of ipomoeassin F. Moreover, ipomoeassin F significantly suppressed TNBC growth in a mouse tumor xenograft model, with a marked reduction in PDIA6 and PDIA4 levels in the tumor samples. Our study demonstrates that Sec61α-containing ER translocon and PDIAs are potential drug targets for TNBC and suggests that ipomoeassin F could serve as a lead for developing ER translocon-targeted therapy for TNBC.

MDM2 inhibition is synthetic lethal with PTEN loss in colorectal cancer cells via the p53-dependent mechanism.

Colorectal cancer (CRC) driven by PTEN deficiency exhibits high risk of metastasis, advancement of tumor stages and chemotherapy resistance, where no effective therapy has been developed. In this study, we performed a synthetic lethal drug screening in CRC and found that PTEN-deficient CRC cells are highly vulnerable to MDM2 inhibition. MDM2 inhibitor treatment or its silencing selectively inhibited the growth of PTEN-deficient CRC in vitro and in mice models. Mechanistically, PTEN loss increased the level of active AKT and subsequently increased MDM2 phosphorylation, thereby limiting the p53 functions in PTEN-/- CRC cells. MDM2 inhibition in turn activated p53 in CRC, particularly in PTEN-/- CRC cells. The synthetic lethal effect of MDM2 inhibitor was largely dependent on p53, because p53 silenced cells or cells lacking p53 failed to exhibit synthetic lethality in PTEN-deficient cells. We further showed that MDM2 inhibition led to the p53-dependent reversal of Bcl2-Bax ratio, which contributed to mitochondria-mediated apoptotic cell death in PTEN-deficient CRC. This study suggests that pharmacological targeting of MDM2 could be a potential therapeutic strategy for PTEN-deficient CRC.

Qualitative analysis on the transdermal absorption from the dichloromethane extract of the Sambucus adnata wall. based on UPLC-Q-Exactive Orbitrap/MS.

Sambucus adnata Wall.(SAW) has been used to treat osteoarthritis by the Yi nationality in China. The present study established an overall identification strategy based on ultra-high performance liquid chromatography-tandem Q-Exactive Orbitrap mass spectrometry (UPLC-Q-Exactive Orbitrap/MS) method to characterize the multiple chemical constituents of SAW before and after percutaneous penetration. Nineteen compounds, including triterpenoids, fatty acids, lignans, flavonoid, and amide, were tentatively identified in the dichloromethane extract of SAW, while fourteen ingredients penetrated the skin. Among them, eleven components were reported for the first time in SAW.

Exorista sorbillans (Diptera: Tachinidae) parasitism shortens host larvae growth duration by regulating ecdysone and juvenile hormone titers in Bombyx mori (Lepidoptera: Bombycidae).

The tachinid fly, Exorista sorbillans, is a notorious ovolarviparous endoparasitoid of the silkworm, Bombyx mori, causing severe damage to silkworm cocoon industry. Silkworm larvae show typically precocious wandering behavior after being parasitized by E. sorbillans; however, the underlying molecular mechanism remains unexplored. Herein, we investigated the changes in the levels of 20-hydroxyecdysone (20E) and juvenile hormone (JH) titer, and they both increased in the hemolymph of parasitized silkworms. Furthermore, we verified the expression patterns of related genes, which showed an upregulation of 20E signaling and biosynthesis genes but a significant downregulation of ecdysone oxidase (EO), a 20E inactivation enzyme, in parasitized silkworms. In addition, related genes of the JH signaling were activated in parasitized silkworms, while related genes of the JH degradation pathway were suppressed, resulting in an increase in JH titer. Notably, the precocious wandering behavior of parasitized silkworms was partly recoverable by silencing the transcriptions of BmCYP302A1 or BmCYP307A1 genes. Our findings suggest that the developmental duration of silkworm post parasitism could be shortened by regulation of 20E and JH titers, which may help silkworm to resist the E. sorbillans infestation. These findings provide a basis for deeper insight into the interplay between silkworms and E. sorbillans and may serve as a reference for the development of a novel approach to control silkworm myiasis.

PD-1 blockade potentiates neoadjuvant chemotherapy in NSCLC via increasing CD127+ and KLRG1+ CD8 T cells.

The combination of PD-1 blockade with neoadjuvant chemotherapy (NAC) has achieved unprecedented clinical success in non-small cell lung cancer (NSCLC) compared to NAC alone, but the underlying mechanisms by which PD-1 blockade augments the effects of chemotherapy remain incompletely elucidated. Single-cell RNA sequencing was performed on CD45+ immune cells isolated from surgically resected fresh tumors of seven NSCLC patients receiving NAC or neoadjuvant pembrolizumab and chemotherapy (NAPC). Multiplex fluorescent immunohistochemistry was performed on FFPE tissues before and after NAC or NAPC from 65 resectable NSCLC patients, and results were validated with GEO dataset. NAC resulted in an increase only of CD20+ B cells, whereas NAPC increased the infiltration of CD20+ B cells, CD4+ T cells, CD4+CD127+ T cells, CD8+ T cells, CD8+CD127+ and CD8+KLRG1+ T cells. Synergistic increase in B and T cells promotes favorable therapeutic response after NAPC. Spatial distribution analysis discovered that CD8+ T cells and their CD127+ and KLRG1+ subsets were in closer proximity to CD4+ T/CD20+ B cells in NAPC versus NAC. GEO dataset validated that B-cell, CD4, memory, and effector CD8 signatures correlated with therapeutic responses and clinical outcomes. The addition of PD-1 blockade to NAC promoted anti-tumor immunity through T and B cells recruitment in the tumor microenvironment and induced tumor-infiltrating CD8+ T cells skewed toward CD127+ and KLRG1+ phenotypes, which may be assisted by CD4+ T cells and B cells. Our comprehensive study identified key immune cell subsets exerting anti-tumor responses during PD-1 blockade therapy and that may be therapeutically targeted to improve upon existing immunotherapies for NSCLC.

1H NMR-based metabolomic study of striatal injury in rats with copper-loaded Wilson's disease by Chinese and Western medicine intervention.

OBJECTIVE: To investigate the metabolic mechanisms of Chinese and Western medicines on the metabolic network of striatal injury in a copper-loaded rat model of Wilson disease (WD) from a metabolomic perspective. METHODS: We divided 60 rats into 4 groups of 15 rats each according to a random number table, namely the control group, the model group, the Bushen Huoxue Huazhuo Recipe group, and the penicillamine group, and subsequently replicated the WD copper-loaded rat model according to the literature method for a total of 12 weeks. From the 7th week onwards, each intervention group was given an equivalent dose of the corresponding drug, and the control and model groups were given an equal volume of saline gavage until the end of the model replication. We used 1H NMR metabolomics techniques combined with multivariate statistical methods to describe the changes in the striatal metabolic profile of nerve injury in Wilson's disease and to analyze the effect of different treatments on their biomarker interventions. RESULTS: Nerve cell damage was evident in the WD copper-loaded rat model and could be reduced to varying degrees by different methods of intervention in the striatal nerve cells. The content of glycine, serine metabolism, and valine metabolism decreased in WD copper-loaded rat model; aspartate content increased after penicillamine intervention; glycolytic metabolism, valine metabolism, taurine metabolism, and tyrosine metabolism increased in the group of Bushen Huoxue Huazhuo Recipe. CONCLUSION: Different intervention methods of Chinese and Western medicine affect aspartate, glycolysis, taurine, tyrosine, valine, and carbon metabolism in striatal tissues of WD copper-loaded rats, and can regulate the metabolism of small molecules, which in turn have certain repairing effects on nerve damage in WD copper-loaded rats.

Adjuvant icotinib versus observation in patients with completely resected EGFR-mutated stage IB NSCLC (GASTO1003, CORIN): a randomised, open-label, phase 2 trial.

Background: This phase 2 trial aimed to compare adjuvant icotinib with observation in patients with epidermal growth factor receptor (EGFR) mutation-positive resected stage IB non-small cell lung cancer (NSCLC). Methods: We performed a randomised, open-label, phase 2 trial from May 1, 2015 to December 29, 2020 at Sun Yat-sen University Cancer Center in China. Patients with completely resected, EGFR-mutant, stage IB (the 7th edition of TNM staging) NSCLC without adjuvant chemotherapy were randomised (1:1) to receive adjuvant therapy with icotinib (125 mg, three times daily) for 12 months or to undergo observation until disease progression or intolerable toxicity occurred. The primary endpoint was 3-year disease-free survival (DFS). CORIN (GASTO1003) was registered with Clinicaltrials.gov, with the number NCT02264210. Findings: A total of 128 patients were randomised, with 63 patients in the icotinib group and 65 patients in the observation group. The median duration of follow-up was 39.9 months. The three-year DFS was significantly higher in the icotinib group (96.1%, 95% confidence interval [CI], 91.3-99.9) than in the observation group (84.0%, 95% CI, 75.1-92.9; P = 0.041). The DFS was significantly longer in the icotinib group than in the observation group, with a hazard ratio (HR) of 0.23 (95% CI, 0.07-0.81; P = 0.013). The OS data were immature, with three deaths in the observation arm. In the icotinib group, adverse events (AEs) of any grade were reported in 49 patients (77.8%), and grade 3 or greater AEs occurred in four patients (6.3%). No treatment-related deaths occurred. Interpretation: Our findings suggested that adjuvant icotinib improved the 3-year DFS in patients with completely resected EGFR-mutated stage IB NSCLC with a manageable safety profile. Funding: This study was sponsored by Betta Pharmaceutical Co., Ltd.

Azithromycin suppresses TGF-ß1-related epithelial-mesenchymal transition in airway epithelial cells via targeting RACK1.

Transforming growth factor-ß1 (TGF-ß1) associated epithelial-mesenchymal transition (EMT) contributes to multiple respiration diseases via Smad or MAPKs pathway. Our previous study has demonstrated that the typical macrolide antibiotic, azithromycin (AZM) played a notable anti-EMT role in ovalbumin (OVA)-challenged mice. However, the precise mechanism of AZM on TGF-ß1 mediated EMT in bronchial epithelial cells is still unclear. The purpose of this study was to elucidate whether azithromycin targeting RACK1 inhibits TGF-ß1 mediated EMT in vitro. The results showed that AZM significantly inhibited the expression of RACK1 and the activation of the downstream JNK, ERK, and Smad3 signaling pathways, thereby suppressing the migration of bronchial epithelial cells and reversing the TGF-ß1-induced EMT. The effect of AZM on TGF-ß1 mediated EMT in vitro is dependent on the dose of AZM. Although RACK1 has been shown to regulate IRE1α expression with siRACK1 transfection, there was no direct interaction between IRE1α and AZM. On the contrary, weak interaction between AZM and RACK1 was predicted with molecular docking. In summary, AZM targets RACK1 to trigger downstream JNK, ERK, and Smad3 signaling pathways and is an effective anti-EMT drug for bronchial epithelial cells in a dose-dependent manner.

Lipotoxicity-induced mtDNA release promotes diabetic cardiomyopathy by activating the cGAS-STING pathway in obesity-related diabetes.

Diabetic cardiomyopathy (DCM) is characterized by lipid accumulation, mitochondrial dysfunction, and aseptic inflammatory activation. Mitochondria-derived cytosolic DNA has been reported to induce inflammation by activating cyclic GMP-AMP synthase (cGAS)/the stimulator of interferon genes (STING) pathway in the adipose, liver, and kidney tissues. However, the role of cytosolic mtDNA in the progression of DCM is unclear. In this study, with an obesity-related DCM mouse model established by feeding db/db mice with a high-fat diet (HFD), we observed increased mtDNA in the cytosol and activated cGAS-STING signaling pathway during DCM, as well as the downstream targets, IRF3, NF-κB, IL-18, and IL-1ß. In a further study with a palmitic acid (PA)-induced lipotoxic cell model established in H9C2 cells, we revealed that the cytosolic mtDNA was the result of PA-induced overproduction of mitochondrial ROS, which also led to the activation of the cGAS/STING system and its downstream targets. Notably, treatment of extracted mtDNA alone was sufficient to activate the cGAS-STING signaling pathway in cultured H9C2 cells. Besides, both knockdown of STING in PA-induced H9C2 cells and inhibition of STING by C-176 injection in the DCM mouse model could remarkably block the inflammation and apoptosis of cardiomyocytes. In conclusion, our study elucidated the critical role of cytosolic mtDNA-induced cGAS-STING activation in the pathogenesis of obesity-related DCM and provided preclinical validation for using a STING inhibitor as a new potential therapeutic strategy for the treatment of DCM.

Genome-Wide Identification and Expression Patterns of AcSWEET Family in Pineapple and AcSWEET11 Mediated Sugar Accumulation.

Pineapple (Ananas comosus L.) is an important fruit crop in tropical regions, and it requires efficient sugar allocation during fruit development. Sugars Will Eventually be Exported Transporters (SWEETs) are a group of novel sugar transporters which play critical roles in seed and fruit development. However, the function of AcSWEETs remains unknown in the sugar accumulation. Herein, 17 AcSWEETs were isolated and unevenly located in 11 chromosomes. Analysis of a phylogenetic tree indicated that 17 genes were classified into four clades, and the majority of AcSWEETs in each clade shared similar conserved motifs and gene structures. Tissue-specific gene expression showed that expression profiles of AcSWEETs displayed differences in different tissues and five AcSWEETs were strongly expressed during fruit development. AcSWEET11 was highly expressed in the stage of mature fruits in 'Tainong16' and 'Comte de paris', which indicates that AcSWEET11 was important to fruit development. Subcellular localization analysis showed that AcSWEET11 was located in the cell membrane. Notably, overexpression of AcSWEET11 could improve sugar accumulation in pineapple callus and transgenic tomato, which suggests that AcSWEET11 might positively contribute to sugar accumulation in pineapple fruit development. These results may provide insights to enhance sugar accumulation in fruit, thus improving pineapple quality in the future.