Predictability comparison of sizing parameters for postoperative vault after implantable Collamer lens implantation.

PURPOSE: This study aims to assess the accuracy of three parameters (white-to-white distance [WTW], angle-to-angle [ATA], and sulcus-to-sulcus [STS]) in predicting postoperative vault and to formulate an optimized predictive model. METHODS: In this retrospective study, a cohort of 465 patients (comprising 769 eyes) who underwent the implantation of the V4c implantable Collamer lens with a central port (ICL) for myopia correction was examined. Least absolute shrinkage and selection operator (LASSO) regression and classification models were used to predict postoperative vault. The influences of WTW, ATA, and STS on predicting the postoperative vault and ICL size were analyzed and compared. RESULTS: The dataset was randomly divided into training (80%) and test (20%) sets, with no significant differences observed between them. The screened variables included only seven variables which conferred the largest signal in the model, namely, lens thickness (LT, estimated coefficients for logistic least absolute shrinkage of -0.20), STS (-0.04), size (0.08), flat K (-0.006), anterior chamber depth (0.15), spherical error (-0.006), and cylindrical error (-0.0008). The optimal prediction model depended on STS (R2=0.419, RMSE=0.139), whereas the least effective prediction model relied on WTW (R2=0.395, RMSE=0.142). In the classified prediction models of the vault, classification prediction of the vault based on STS exhibited superior accuracy compared to ATA or WTW. CONCLUSIONS: This study compared the capabilities of WTW, ATA, and STS in predicting postoperative vault, demonstrating that STS exhibits a stronger correlation than the other two parameters.

Observing the clinical efficacy of combined serum microneedle therapy for moderate to severe androgenetic alopecia in scalp repair.

OBJECTIVE: In this study, the safety and efficacy of scalp repair serum microneedles combined with oral drug administration and topical medication were investigated for the treatment of moderate to severe androgenetic alopecia. METHODS: Twenty patients, consisting of 4 males and 16 females, who sought treatment for moderate to severe androgenetic alopecia at our hair medicine research center alopecia specialty clinic between August and December 2022 were randomly selected for the study. Male patients underwent oral administration of finasteride topical application of 5% minoxidil, and biweekly scalp repair serum microneedle therapy. Female patients were administered spironolactone or Diane-35 orally and applied 2% minoxidil topically, paired with biweekly scalp repair serum microneedle therapy sessions. After seven treatments, the scalp repair serum microneedle was discontinued, but oral administration and topical applications were continued, followed by a 1-month follow-up. Using a hair dermoscopy, hair follicles in a fixed region on the top of the head were manually counted per unit area to evaluate the hair restoration status of the patients quantitatively. RESULTS: All 20 patients completed 3 months of combined therapy and a 1-month follow-up. On average, the patients experienced an increase of 42.6 hairs, with an efficiency rate of 100%. Significant differences were observed in hair count between any two of the first seven treatments (p < 0.001). A significant negative correlation was discovered between the initial pre-treatment hair count and the total improvement of hair (p < 0.001), indicating that the greater the degree of hair loss before treatment, the more pronounced the improvement. CONCLUSION: Scalp repair serum microneedle combined therapy in moderate to severe androgenetic alopecia significantly reduces the number of microneedle treatments required, enhances treatment efficacy, and improves therapeutic outcomes.

The Combination of Sinusoidal Perfusion Enhancement and Apoptosis Inhibition by Riociguat Plus a Galactose-PEGylated Bilirubin Multiplexing Nanomedicine Ameliorates Liver Fibrosis Progression.

Chronic liver injury and continuous wound healing lead to extracellular matrix (ECM) deposition and liver fibrosis. The elevated production of reactive oxygen species (ROS) in the liver leads to the apoptosis of hepatocytes and the activation of hepatic stellate cells (HSCs). In the current study, we describe a combination strategy of sinusoidal perfusion enhancement and apoptosis inhibition enabled by riociguat together with a tailor-designed galactose-PEGylated bilirubin nanomedicine (Sel@GBRNPs). Riociguat enhanced sinusoidal perfusion and decreased the associated ROS accumulation and inflammatory state of the fibrotic liver. Concurrently, hepatocyte-targeting galactose-PEGylated bilirubin scavenged excessive ROS and released encapsulated selonsertib. The released selonsertib inhibited apoptosis signal-regulating kinase 1 (ASK1) phosphorylation to alleviate apoptosis in hepatocytes. The combined effects on ROS and hepatocyte apoptosis attenuated the stimulation of HSC activation and ECM deposition in a mouse model of liver fibrosis. This work provides a novel strategy for liver fibrosis treatment based on sinusoidal perfusion enhancement and apoptosis inhibition.

Trihelix transcription factor SlGT31 regulates fruit ripening mediated by ethylene in tomato.

Trihelix proteins are plant-specific transcription factors that are classified as GT factors due to their binding specificity for GT elements, and they play crucial roles in development and stress responses. However, their involvement in fruit ripening and transcriptional regulatory mechanisms remains largely unclear. In this study, we cloned SlGT31, encoding a trihelix protein in tomato (Solanum lycopersicum), and determined that its relative expression was significantly induced by the application of exogenous ethylene whereas it was repressed by the ethylene-inhibitor 1-methylcyclopropene. Suppression of SlGT31 expression resulted in delayed fruit ripening, decreased accumulation of total carotenoids, and reduced ethylene content, together with inhibition of expression of genes related to ethylene and fruit ripening. Conversely, SlGT31-overexpression lines showed opposite results. Yeast one-hybrid and dual-luciferase assays indicated that SlGT31 can bind to the promoters of two key ethylene-biosynthesis genes, ACO1 and ACS4. Taken together, our results indicate that SlGT31 might act as a positive modulator during fruit ripening.

The AP2/ERF transcription factor SlERF.J2 functions in hypocotyl elongation and plant height in tomato.

KEY MESSAGE: Our findings indicated that the SlERF.J2-IAA23 module integrates hormonal signals to regulate hypocotyl elongation and plant height in tomato. Light and phytohormones can synergistically regulate photomorphogenesis-related hypocotyl elongation and plant height in tomato. AP2/ERF family genes have been extensively demonstrated to play a role in light signaling and various hormones. In this study, we identified a novel AP2/ERF family gene in tomato, SlERF.J2. Overexpression of SlERF.J2 inhibits hypocotyl elongation and plant height. However, the plant height in the slerf.j2ko knockout mutant was not significantly changed compared with the WT. we found that hypocotyl cell elongation and plant height were regulated by a network involving light, auxin and gibberellin signaling, which is mediated by regulatory relationship between SlERF.J2 and IAA23. SlERF.J2 protein could bind to IAA23 promoter and inhibit its expression. In addition, light-dark alternation can activate the transcription of SlERF.J2 and promote the function of SlERF.J2 in photomorphogenesis. Our findings indicated that the SlERF.J2-IAA23 module integrates hormonal signals to regulate hypocotyl elongation and plant height in tomato.

Highly specific neutrophil-mediated delivery of albumin nanoparticles to ectopic lesion for endometriosis therapy.

Endometriosis is an estrogen-dependent chronic inflammatory disease. Hormonal and surgical treatments are the most commonly used clinical therapies, but they have many sides effects or are traumatic to the body. Therefore, specific drugs for endometriosis treatment are urgently needed to develop. In this study, we identified two features of endometriosis, namely the continuous recruitment of neutrophils into the ectopic lesions and the higher uptake of glucose by ectopic cells. For the above features, we designed a glucose oxidase-loaded bovine serum albumin nanoparticle (BSA-GOx-NPs) that is inexpensive and facilitates large-scale production. After injection, BSA-GOx-NPs were high specifically delivered to ectopic lesions in a neutrophil-dependent manner. Furthermore, BSA-GOx-NPs deplete glucose and induce apoptosis in the ectopic lesions. Whereupon BSA-GOx-NPs produced excellent anti-endometriosis effects when administrated in both acute and chronic inflammatory phases. These results reveal for the first time that the neutrophil hitchhiking strategy is effective in chronic inflammatory disease and provide a non-hormonal and easy-to-achieve approach for endometriosis treatment.

Self-assembly of molecular beacons through metal ion coordination for fluorescence imaging of miRNA in living cells.

Fluorescence nanosensors based on functional nucleic acids have been explored as a powerful sensing platform for disease-relevant miRNAs. This work developed a new hybrid nanosensor (Zr-B) through coordination-driven self-assembly of Zr ions and beacons. The prepared nanosensor exhibited high loading efficiency of beacons and could achieve sensitive and specific detection for miRNAs. The hybrid nanosensor could transfer beacons into living cells efficiently and maintain high stability and biocompatibility in the biological environment, achieving effective miRNA fluorescence imaging in living cells. Therefore, the resultant nanosensor holds potential for applications in disease diagnostics.

Pyrimidine-conjugated fluoroquinolones as new potential broad-spectrum antibacterial agents.

Pyrimidine-conjugated fluoroquinolones were constructed to cope with the dreadful resistance. Most of the target pyrimidine derivatives effectively suppressed the growth of the tested strains, especially, 4-aminopyrimidinyl compound 1c showed a broad antibacterial spectrum and low cytotoxicity and exhibited superior antibacterial potency against Enterococcus faecalis with a low MIC of 0.25 µg/mL to norfloxacin and ciprofloxacin. The active compound 1c with fast bactericidal potency could inhibit the formation of biofilms and showed much lower trend for the development of drug-resistance than norfloxacin and ciprofloxacin. Further exploration revealed that compound 1c could prompt ROS accumulations in bacterial cells and interact with DNA to form a DNA-1c complex, thus facilitating bacterial death. ADME analysis indicated that compound 1c possessed favorable drug-likeness and promising pharmacokinetic properties. These results demonstrated that pyrimidine-conjugated fluoroquinolones held hope as potential antibacterial candidates and deserve further study.

Novel metronidazole-derived three-component hybrids as promising broad-spectrum agents to combat oppressive bacterial resistance.

The dreadful bacterial resistance to clinical drugs calls for the development of novel antibacterials. This work developed a class of unique metronidazole-derived three-component hybrids as promising antibacterial therapeutic alternatives. Bioactive assay discovered that p-chlorophenylhydrazone derivative 6b possessed excellent ability to suppress the growth of drug-resistant E. coli (MIC = 0.5 µg/mL), being 16 folds more potent than norfloxacin (MIC = 8 µg/mL). The active molecule 6b with imperceptible hemolysis could effectively retard the development of bacterial drug resistance within 30 passages. Moreover, compound 6b displayed a favorable inhibitory effect on E. coli biofilms and could act rapidly in bactericidal efficacy. Subsequent exploration of mechanism revealed that 6b could destruct the bacterial cytoplasmic membrane, leading to the leakage of intracellular protein. The inactivation of lactate dehydrogenase, metabolic stagnation and the accumulation of reactive oxygen species caused by 6b were observed. Furthermore, molecule 6b could form a supramolecular complex with DNA to obstruct DNA replication. These results demonstrated that metronidazole-derived three-component hybrids provided a large potential for deep development as prospective antibacterial agents.

Novel SOX2 mutation in autosomal dominant cataract-microcornea syndrome.

BACKGROUND: Congenital cataract-microcornea syndrome (CCMC) is characterized by the association of congenital cataract and microcornea without any other systemic anomaly or dysmorphism. Although several causative genes have been reported in patients with CCMC, the genetic etiology of CCMC is yet to be clearly understood. PURPOSE: To unravel the genetic cause of autosomal dominant family with CCMC. METHODS: All patients and available family members underwent a comprehensive ophthalmologic clinical examination in the hospital by expert ophthalmologists and carried out to clinically diagnosis. All the patients were screened by whole-exome sequencing and then validated using co-segregation by Sanger sequencing. RESULTS: Four CCMC patients from a Chinese family and five unaffected family members were enrolled in this study. Using whole-exome sequencing, a missense mutation c.295G > T (p.A99S, NM_003106.4) in the SOX2 gene was identified and validated by segregation analysis. In addition, this missense mutation was predicted to be damaging by multiple predictive tools. Variant p.Ala99Ser was located in a conservation high mobility group (HMG)-box domain in SOX2 protein, with a potential pathogenic impact of p.Ala99Ser on protein level. CONCLUSIONS: A novel missense mutation (c.295G > T, p.Ala99Ser) in the SOX2 gene was found in this Han Chinese family with congenital cataract and microcornea. Our study determined that mutations in SOX2 were associated with CCMC, warranting further investigations on the pathogenesis of this disorder. This result expands the mutation spectrum of SOX2 and provides useful information to study the molecular pathogenesis of CCMC.

The Protective Effects of Neoastilbin on Monosodium Urate Stimulated THP-1-Derived Macrophages and Gouty Arthritis in Mice through NF-κB and NLRP3 Inflammasome Pathways.

Gouty arthritis (GA) is a frequent inflammatory disease characterized by pain, swelling, and stiffness of joints. Neoastilbin is a flavonoid isolated from the rhizome of Smilax glabra, which possesses various anti-inflammatory effects. However, the mechanism of neoastilbin in treating GA has not yet been clarified. Thus, this study was to investigate the protective effects of neoastilbin in both monosodium urate (MSU) stimulated THP-1-derived macrophages and the animal model of GA by injecting MSU into the ankle joints of mice. The levels of key inflammatory cytokines in MSU stimulated THP-1-derived macrophages were detected by enzyme-linked immunosorbent assay (ELISA) kits. Protein expressions of nuclear factor kappa B (NF-κB) and NOD-like receptor protein 3 (NLRP3) inflammasome pathways were further detected by Western blotting. In addition, swelling degree of ankle joints, the levels of inflammatory factors, infiltration of inflammatory cells and the expressions of related proteins were determined. Swelling degree and histopathological injury in ankle joints of MSU-injected mice were significantly decreased after being treated with neoastilbin. Moreover, neoastilbin significantly diminished the secretion of interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), suppressing the activation of NF-κB and NLRP3 inflammasome pathways in both MSU stimulated THP-1-derived macrophages and the mouse model of GA. In summary, neoastilbin could alleviate GA by inhibiting the NF-κB and NLRP3 inflammasome pathways, which provided some evidence for neoastilbin as a promising therapeutic agent for GA treatment.

Road Injuries Associated With Cellular Phone Use While Walking or Riding a Bicycle or an Electric Bicycle: A Case-Crossover Study.

Vulnerable road users (pedestrians, bicyclists, and motorcyclists) account for an increasing proportion of traffic injuries. We used a case-crossover study design to examine the association between cell-phone usage and traffic injuries among pedestrians, bicyclists, and electric bicycle riders during the course of their travel. We studied 643 pedestrians, bike riders, and electric bike riders aged 10-35 years who were involved in a road injury, visited the emergency department in one of the 3 hospitals in Shanghai, China, in 2019, and owned a cell phone. Half of the participants (n = 323; 50.2%) had used a cell phone within 1 minute before the injury happened. A pedestrian's or rider's use of a mobile phone up to 1 minute before a road injury was associated with a 3-fold increase in the likelihood of injury (odds ratio = 3.00, 95% confidence interval: 2.04, 4.42; P < 0.001). The finding was consistent across subgroups by sex, occupation, reason for travel, mode of transportation, and location of injury. Use of a cell phone when walking or riding was associated with an increased risk of road injury. Measures should be taken to make people aware of this detrimental impact on the risk of road injury.

Postnatal leptin surge is critical for the transient induction of the developmental beige adipocytes in mice.

Beige adipocytes have become a promising therapeutic target to combat obesity. Our senior author Dr. B. Xue previously discovered a transient but significant induction of beige adipocytes in mice during early postnatal development, which peaked at postnatal day (P) 20 and then disappeared thereafter. However, the physiological mechanism underlying the transient induction of the developmental beige cells remains mystery. Interestingly, there exists a postnatal surge of leptin in mice at P10 before the appearance of the developmental beige adipocytes. Given the neurotropic effect of leptin during neuronal development and its role in activating the sympathetic nervous system (SNS), we tested the hypothesis that postnatal leptin surge is required for the transient induction of developmental beige adipocytes through sympathetic innervation. Unlike wild-type (WT) mice that were able to acquire the developmentally induced beige adipocytes at P20, ob/ob mice had much less uncoupling protein 1 (UCP1)-positive multilocular cells in inguinal white adipose tissue at the same age. This was consistent with reduced expression of UCP1 mRNA and protein levels in white fat of ob/ob mice. In contrast, daily injection of ob/ob mice with leptin between P8 and P16, mimicking the postnatal leptin surge, largely rescued the ability of these mice to acquire the developmentally induced beige adipocytes at P20, which was associated with enhanced sympathetic nerve innervation assessed by whole mount adipose tissue immunostaining of tyrosine hydroxylase. Our data demonstrate that the postnatal leptin surge is essential for the developmentally induced beige adipocyte formation in mice, possibly through increasing sympathetic nerve innervation.

Core competencies for injury prevention among public health students and an advocacy for curriculum development in the medical universities in China: a cross-sectional study.

OBJECTIVES: To assess the current status of injury prevention (IP) core competency among medical students majoring in public health in China and to advocate for incorporating IP in the medical curriculum. METHODS: The study used purposive sampling in eight medical universities in China in 2017, including 420 undergraduates and 763 graduates, using self-administered questionnaires based on the core competency instrument for IP with five domains (31 items): A) injury analysis and assessment (8 items), B) IP project planning and implementation (7 items), C) communication (6 items), D) community practice (5 items), and E) leadership and systematic thinking (5 items). The higher score indicated the higher level of proficiency of the ability (scores ranged from 1 to 5). We used linear regression model to test the effect of IP course experience on the core competency mean score after adjusting for potential confounders. RESULTS: The total mean score was 2.78 (SD=0.76, median=2.9, range=1-4.55) and 2.68 (SD=0.75, median=2.81, range=1-4.45) for undergraduates and graduates, respectively. There were 60% and 36% of undergraduates and graduates who have ever taken IP course, respectively. IP course class hours were positively associated with core competency level (P<0.05) across five domains (except for domain D) and the total. CONCLUSION: The core competency level is relatively low among public health students in China. Setting IP courses should be considered as an effective way to improve students' core competency. It is a step moving towards the IP education promotion, and further boosting the field of public health.

ß-TrCP-mediated ubiquitination and degradation of Dlg5 regulates hepatocellular carcinoma cell proliferation.

BACKGROUND: Discs large homolog 5 (Dlg5) is a member of the membrane-associated guanylate kinase (MAGUK) adaptor family of proteins and its deregulation has been implicated in the malignancy of several cancer types. Dlg5 was down-regulated in hepatocellular carcinoma (HCC) and lower Dlg5 expression was associated with poor survival of HCC patients. However, how to regulate Dlg5 remains largely unknown. METHODS: The co-immunoprecipitation assay was used to determine the interaction between Dlg5 and ß-TrCP. The in vivo ubiquitination assay was performed to determine the regulation of Dlg5 by ß-TrCP. CCK-8 and colony formation assay were implemented to detect the biological effect of Dlg5 on the growth of HCC cells in vitro. The effect of Dlg5 on HCC tumor growth in vivo was studied in a tumor xenograft model in mice. RESULTS: Here we report that Dlg5 is regulated by the ubiquitin proteasome system and depletion of either Cullin 1 or ß-TrCP led to increased levels of Dlg5. ß-TrCP regulated Dlg5 protein stability by targeting it for ubiquitination and subsequent destruction in a phosphorylation-dependent manner. We further demonstrated a crucial role of Ser730 in the non-canonical phosphodegron of Dlg5 in governing ß-TrCP-mediated Dlg5 degradation. Importantly, failure to degrade Dlg5 significantly inhibited HCC cells proliferation both in vitro and in vivo. CONCLUSION: Collectively, our finding provides a novel molecular mechanism for the negative regulation of Dlg5 by ß-TRCP in HCC cells. It further suggests that preventing Dlg5 degradation could be a possible novel strategy for clinical treatment of HCC.

The bHLH transcription factor SlPRE2 regulates tomato fruit development and modulates plant response to gibberellin.

KEY MESSAGE: SlPRE2 is gibberellin inducible and mediates plant response to gibberellin. Silencing of SlPRE2 decreases tomato fruit size, pericarp thickness, placenta size and seed size by regulating cell expansion. Gibberellin is one of the crucial hormones essential for plant growth and developmental processes, including seed germination, stem elongation, and sex expression. Previous studies indicated gibberellin could control fruit development by regulation of genes downstream gibberellin pathway. In the present study, we found that the SlPRE2, a bHLH family transcription factor gene, is highly expressed in immature green fruit. Silencing of SlPRE2 caused reduction of fruits size, pericarp thickness, and placenta size. Meanwhile, smaller seeds were observed in SlPRE2 silenced lines. In addition, the SlPRE2-silenced fruit mesocarp had reduced cell size and expression of SlXTH2 and SlXTH5 which are involved in cell enlargement. Further research showed that SlPRE2 is gibberellic acid-inducible and the expression of gibberellin metabolism-related genes in immature green fruit was affected by the downregulation of SlPRE2. Moreover, the SlPRE2-silenced plants had changed responses to application of exogenous gibberellic acid and paclobutrazol, an inhibitor of gibberellin biosynthesis. These findings indicated that SlPRE2 is a regulator of fruit development and affects plant response to gibberellic acid via the gibberellin pathway.

"Magnus nano-bullets" as T1/T2 based dual-modal for in vitro and in vivo MRI visualization.

Tissue specific T1/T2 dual contrast abilities for magnetic resonance imaging (MRI) have great significance in initial detection of cancer lesions. Herein, we developed a novel kind of Magnus nano-bullets (Mn-DTPA-F-MSNs) distinguished by magnetic (Fe3O4-NPs) head combined with mesoporous (SiO2) persist body, respectively. Subsequently, modify mesoporous SiO2 group and finally loaded with Mn2+. These Magnus nano-bullets have relaxivity value (r1 = 5.12 mM-1 s-1) and relaxivity value (r2 = 265.32 mM-1 s-1); they were > 2 folds in comparison to control at 3.0 T. Meanwhile, Magnus nano-bullets also offered significant enhancements for the detection of Glutathione (GSH), a biomarker that has been showed a redox responsive T1-weighted MRI effect in vitro and in vivo evaluations with good biocompatibility. Therefore, our finding endorses that Magnus nano-bullets offer a "smart" and tremendous strategy for greater GSH responsive T1/T2 dual MRI image probes for future biomedical applications.

Hydrophobically Modified Glucan as an Amphiphilic Carbohydrate Polymer for Micellar Delivery of Myricetin.

Myricetin (Myr) is a phytochemical with many functional properties. However, its hydrophobicity, low bioavailability, and stability limit its application. In this study, octadecanoate oat ß-glucan (OGE) was synthesized and gained recognition as a self-assembled micelle forming a polymer with a critical micelle concentration (CMC) of 59.4 µg/mL. The Myr-loaded OGE micelle was then prepared and characterized by dynamic light scattering (DLS), transmission electron microscope (TEM), X-ray diffractometer (XRD), and Fourier-transform infrared spectroscopy (FT-IR) spectra. The water solubility of Myr was greatly enhanced by forming the Myr/OGE inclusion complex. Consequently, compared to free Myr, the retention of Myr in Myr-loaded OGE micelle was effectively increased during the intestinal digestion phase, and its antioxidant activity was also improved. Overall, our findings demonstrated the potential applications of OGE polymer for the development of prospective micelle in health food, cosmetics, and pharmaceutical fields because they can aid in the delivery of hydrophobic functional compounds like Myr.

Simulation of blood and oxygen distributions in a hepatic lobule with sinusoids obstructed by cancer cells.

The liver is one of the common metastatic sites for many cancers. The obstruction of sinusoids by circulating tumor cells changes liver microenvironments and is thus considered a source of hepatic metastases. To date, few studies provide detailed information, either experimentally or theoretically, concerning the changes in blood and oxygen distributions induced by the obstruction of sinusoids. In this study, we utilized a 3D porous medium-vascular tree geometric structure to mimic the hepatic lobule and studied theoretical blood flow and oxygen transport in the lobule. The simulation was validated with data from the literature. Then, the distributions of blood and oxygen in the presence of the obstruction by cancer cells were simulated. The area and degree of the liver damage induced by the obstruction were analyzed by comparing the difference of liver microenvironments between physiological (non-blocked sinusoid) and pathological (fully or partially blocked sinusoid) conditions and the minimum cancer cell sizes causing liver damage for various obstruction positions were obtained. The work presented in this study can be used to predict the degree of liver damage induced by the local ischemia caused by the obstruction of sinusoids and to characterize the relationship between hepatic metastases and liver microenvironments.

A histone deacetylase gene, SlHDA3, acts as a negative regulator of fruit ripening and carotenoid accumulation.

KEY MESSAGE: SlHDA3 functions as an inhibitor and regulates tomato fruit ripening and carotenoid accumulation. Post-translational modifications, including histones acetylation, play a pivotal role in the changes of chromatin structure dynamic modulation and gene activity. The regulation of histone acetylation is achieved by the action of histone acetyltransferases and deacetylases, which play crucial roles in the regulation of transcription activation. There is an increasing research focus on histone deacetylation in crops, but the role of histone deacetylase genes (HDACs) in tomato has not been elucidated. With the aim of characterizing the tomato RPD3/HDA1 family histone deacetylase genes, SlHDA3 was isolated and its RNA interference (RNAi) lines was obtained. The fruit of SlHDA3 RNAi lines exhibited accelerated ripening process along with short shelf life characteristics. The accumulation of carotenoid was increased due to the alteration of the carotenoid pathway flux. Climacteric ethylene production also stimulated along with significantly up-regulated expression of ethylene biosynthetic genes (ACS2, ACS4, ACO1 and ACO3) and fruit ripening-associated genes (RIN, E4, E8, PG, Pti4, LOXB, Cnr and TAGL1) in SlHDA3 RNAi lines. Besides, fruit cell wall metabolism-associated genes (HEX, MAN, TBG4, XTH5 and XYL) were enhanced in transgenic lines. Relative to wild type (WT) plants, SlHDA3 RNAi seedlings displayed shorter hypocotyls and more sensitivity to ACC (1-aminocyclopropane-1-carboxylate). These results indicated that SlHDA3 is involved in the regulation of fruit ripening by affecting ethylene biosynthesis and carotenoid accumulation.