Factors affecting the scientific research ability and the corresponding countermeasures in clinical postgraduates.

BACKGROUND: Scientific research ability (SRA) is very important for clinical postgraduates. However, the factors affecting students' SRA are constantly changing with the development of medicine. The aim of this study was to investigate the current situation of SRA in clinical postgraduates and exploring the potential factors and the corresponding countermeasures under the background of new medical science. METHODS: A total of 133 postgraduates (first- or second-year) were investigated by questionnaire in the Second Affiliated Hospital of Fujian Medical University. All results were analyzed by R software. RESULTS: In terms of the SRA, academic-degree postgraduate students (ADPSs) were significantly better than professional-degree postgraduate students (PDPSs) (P = 0.001), the students with scientific research interest were remarkably better than those without scientific research interest (P = 0.004), the students who mastered statistical analysis methods were more prominent than those who did not (P = 0.007), the students with paper-writing skills were obviously superior to those without it (P = 0.003), and the second-year students were notably better than the first-year students (P = 0.003). Stratified analysis by the above factors except the degree type showed no significant difference in the first-year postgraduates. In the second-year postgraduates, the ADPSs were remarkably superior to the PDPSs (P = 0.002), the students with scientific research interest were obviously better than those without scientific research interest (P = 0.014), the students with more time investment in scientific research were more prominent than those with less time investment in scientific research (P = 0.025), the students with paper-writing skills were notably superior to those without it (P = 0.031), and the students with plotting ability were better than those without it (P = 0.013). CONCLUSION: The important factors affecting the SRA of clinical postgraduates include the degree type, the grade of student, scientific research interest, time investment in scientific research, statistical analysis methods, paper-writing skills, plotting ability. In short, earlier systematic SRA training contributes to the improvement of SRA in clinical postgraduates, especially in PDPSs.

Antibacterial Properties and Potential Mechanism of Serum from Chinese Alligator.

The Chinese alligator (Alligator sinensis) is an ancient reptile with strong immunity that lives in wetland environments. This study tested the antibacterial ability of Chinese alligator serum (CAS) against Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa and analyzed the potential underlying mechanisms. Results showed that the CAS had a marked antibacterial effect on K. pneumoniae, E. coli, and P. aeruginosa, while S. aureus was only mildly affected. However, these effects disappeared when Protease K was added to the serum. The serum proteome analysis revealed that the antibacterial ability of CAS was produced by interactions among various proteins and that the complement proteins played a major antibacterial role. Therefore, we made relevant predictions about the structure and function of complement component 3. In addition, sequence alignment and phylogenetic analysis of complement component 3d (C3d) in four mammalian species and two alligator species showed that the amino acids that make up the acid pocket on the concave surface of alligator C3d are not identical to those in mammals. This study provided evidence that CAS elicits significant antibacterial effects against some pathogens and provides the basis for further development of novel antibacterial drugs.

Incubation determines favorable microbial communities in Chinese alligator nests.

Nest materials are a major heat source due to rotting promoted by microbial activity. Additionally, they are a potential microbial source given their direct contact with eggshells. Microbial dynamics during incubation have been studied in wild birds; however, similar studies in reptiles remain elusive. Here, the study characterized microbial communities in the nest materials of Chinese alligator (Alligator sinensis) using high-throughput sequencing of bacterial 16S rRNA genes and fungal internal transcribed spacer (ITS) region sequences. The results showed that significant changes in the diversity and structure of microbial communities according to different incubation periods. The diversity and richness of bacterial species increased significantly over time, but the relative abundance of the most dominant bacteria in pre-incubation period, including some pathogenic bacteria, declined after incubation. In contrast, fungal species diversity and richness decreased significantly with time. Additionally, nest material composition significantly influenced microbial community structure rather than species diversity and richness. Notably, the fungal community structure showed a stronger response than bacteria to nest material composition, which varied due to differences in plant litter composition. Our results demonstrate the significant response of microbial community diversity and structure to differences in incubation periods and nest material composition in reptiles. It is further emphasized that the importance of incubation period in the conservation of the Chinese alligator and could inform similar studies in other reptiles and birds.

Sexual Dimorphism of the Gut Microbiota in the Chinese Alligator and Its Convergence in the Wild Environment.

The gut microbiota forms a complex microecosystem in vertebrates and is affected by various factors. As a key intrinsic factor, sex has a persistent impact on the formation and development of gut microbiota. Few studies have analyzed sexual dimorphism of gut microbiota, particularly in wild animals. We used 16S rRNA gene sequencing to analyze the gut microbiota of juvenile and adult Chinese alligators, and untargeted metabolomics to study serum metabolomes of adult alligators. We observed significant sexual differences in the community diversity in juvenile, but not adult, alligators. In terms of taxonomic composition, the phylum Fusobacteriota and genus Cetobacterium were highly abundant in adult alligators, similar to those present in carnivorous fishes, whereas the gut microbiota composition in juvenile alligators resembled that in terrestrial reptiles, indicating that adults are affected by their wild aquatic environment and lack sex dimorphism in gut microbiota. The correlation analysis revealed that the gut microbiota of adults was also affected by cyanobacteria in the external environment, and this effect was sex-biased and mediated by sex hormones. Overall, this study reveals sexual differences in the gut microbiota of crocodilians and their convergence in the external environment, while also providing insights into host-microbiota interactions in wildlife.

Sex-Biased miRNAs in the Gonads of Adult Chinese Alligator (Alligator sinensis) and Their Potential Roles in Sex Maintenance.

MicroRNA (miRNA) is a category of single-stranded non-coding small RNA (sRNA) that regulates gene expression by targeting mRNA. It plays a key role in the temperature-dependent sex determination of Chinese alligator (Alligator sinensis), a reptile whose sex is determined solely by the temperature during the incubation period and remains stable thereafter. However, the potential function of miRNAs in the gonads of adult Chinese alligators is still unclear. Here, we prepared and sequenced sRNA libraries of adult female and male alligator gonads, from breeding (in summer) and hibernating (in winter) animals. We obtained 130 conserved miRNAs and 683 novel miRNAs, which were assessed for sex bias in summer and winter; a total of 65 miRNAs that maintained sex bias in both seasons were identified. A regulatory network of sex-biased miRNAs and genes was constructed. Sex-biased miRNAs targeted multiple genes in the meiosis pathway of adult Chinese alligator oocytes and the antagonistic gonadal function maintenance pathway, such as MOS, MYT1, DMRT1, and GDF9. Our study emphasizes the function of miRNA in the epigenetic mechanisms of sex maintenance in crocodilians.

Exhausting T Cells During HIV Infection May Improve the Prognosis of Patients with COVID-19.

T-cell reduction is an important characteristic of coronavirus disease 2019 (COVID-19), and its immunopathology is a subject of debate. It may be due to the direct effect of the virus on T-cell exhaustion or indirectly due to T cells redistributing to the lungs. HIV/AIDS naturally served as a T-cell exhaustion disease model for recognizing how the immune system works in the course of COVID-19. In this study, we collected the clinical charts, T-lymphocyte analysis, and chest CT of HIV patients with laboratory-confirmed COVID-19 infection who were admitted to Jin Yin-tan Hospital (Wuhan, China). The median age of the 21 patients was 47 years [interquartile range (IQR) = 40-50 years] and the median CD4 T-cell count was 183 cells/µl (IQR = 96-289 cells/µl). Eleven HIV patients were in the non-AIDS stage and 10 were in the AIDS stage. Nine patients received antiretroviral treatment (ART) and 12 patients did not receive any treatment. Compared to the reported mortality rate (nearly 4%-10%) and severity rate (up to 20%-40%) among COVID-19 patients in hospital, a benign duration with 0% severity and mortality rates was shown by 21 HIV/AIDS patients. The severity rates of COVID-19 were comparable between non-AIDS (median CD4 = 287 cells/µl) and AIDS (median CD4 = 97 cells/µl) patients, despite some of the AIDS patients having baseline lung injury stimulated by HIV: 7 patients (33%) were mild (five in the non-AIDS group and two in the AIDS group) and 14 patients (67%) were moderate (six in the non-AIDS group and eight in the AIDS group). More importantly, we found that a reduction in T-cell number positively correlates with the serum levels of interleukin 6 (IL-6) and C-reactive protein (CRP), which is contrary to the reported findings on the immune response of COVID-19 patients (lower CD4 T-cell counts with higher levels of IL-6 and CRP). In HIV/AIDS, a compromised immune system with lower CD4 T-cell counts might waive the clinical symptoms and inflammatory responses, which suggests lymphocyte redistribution as an immunopathology leading to lymphopenia in COVID-19.

Sex-Biased Gene Expression and Evolution in the Cerebrum and Syrinx of Chinese Hwamei (Garrulax canorus).

It is common that males and females display sexual dimorphisms, which usually result from sex-biased gene expression. Chinese hwamei (Garrulax canorus) is a good model for studying sex-biased gene expression because the song between the sexes is quite different. In this study, we analyze cerebrum and syrinx sex-biased gene expression and evolution using the de novo assembled Chinese hwamei transcriptome. In both the cerebrum and syrinx, our study revealed that most female-biased genes were actively expressed in females only, while most male-biased genes were actively expressed in both sexes. In addition, both male- and female-biased genes were enriched on the putative Z chromosome, suggesting the existence of sexually antagonistic genes and the insufficient dosage compensation of the Z-linked genes. We also identified a 9 Mb sex linkage region on the putative 4A chromosome which enriched more than 20% of female-biased genes. Resultantly, male-biased genes in both tissues had significantly higher Ka/Ks and effective number of codons (ENCs) than unbiased genes, and this suggested that male-biased genes which exhibit accelerated divergence may have resulted from positive selection. Taken together, our results initially revealed the reasons for the differences in singing behavior between males and females of Chinese hwamei.

Genome-Wide DNA Methylation and Transcriptome Analyses Reveal Epigenetic and Genetic Mechanisms Underlying Sex Maintenance of Adult Chinese Alligator.

The sexes of Chinese alligators are determined during embryonic development and remain fixed thereafter. In this study, we investigated the genetic and epigenetic mechanisms underlying sex maintenance in Chinese alligators through RNA sequencing and bisulfite sequencing data analyses of the adult gonads. We identified the genes and pathways (e. g., DMRT1-SOX9-AMH pathway for males and oocyte meiotic maturation pathway for females) involved in male and female sex maintenance and gonadal development of adult Chinese alligators. In contrast to their expression patterns in the embryo, both DMRT1 and the steroid hormone biosynthesis related genes showed a male-biased expression in adult gonads. The overall DNA methylation density and level were higher in testes than in ovaries. Hypermethylation in the gene bodies enhanced the expression of male-biased genes (such as DMRT1-SOX9-AMH and steroid hormone biosynthesis related genes) in the testis, as opposed to the normalization of gene expression. Our results provide insights into the genetic and epigenetic mechanisms underlying sex maintenance in adult Chinese alligators, and are expected to contribute to the development of scientific programs for the successful conservation of this endangered species.

HflX is a GTPase that controls hypoxia-induced replication arrest in slow-growing mycobacteria.

GTPase high frequency of lysogenization X (HflX) is highly conserved in prokaryotes and acts as a ribosome-splitting factor as part of the heat shock response in Escherichia coli. Here we report that HflX produced by slow-growing Mycobacterium bovis bacillus Calmette-Guérin (BCG) is a GTPase that plays a critical role in the pathogen's transition to a nonreplicating, drug-tolerant state in response to hypoxia. Indeed, HflX-deficient M. bovis BCG (KO) replicated markedly faster in the microaerophilic phase of a hypoxia model that resulted in premature entry into dormancy. The KO mutant displayed hallmarks of nonreplicating mycobacteria, including phenotypic drug resistance, altered morphology, low intracellular ATP levels, and overexpression of Dormancy (Dos) regulon proteins. Mice nasally infected with HflX KO mutant displayed increased bacterial burden in the lungs, spleen, and lymph nodes during the chronic phase of infection, consistent with the higher replication rate observed in vitro in microaerophilic conditions. Unlike fast growing mycobacteria, M. bovis BCG HlfX was not involved in antibiotic resistance under aerobic growth. Proteomics, pull-down, and ribo-sequencing approaches supported that mycobacterial HflX is a ribosome-binding protein that controls translational activity of the cell. With HflX fully conserved between M. bovis BCG and M. tuberculosis, our work provides further insights into the molecular mechanisms deployed by pathogenic mycobacteria to adapt to their hypoxic microenvironment.

Chromosome-scale genomes provide new insights into subspecies divergence and evolutionary characteristics of the giant panda.

Extant giant pandas are divided into Sichuan and Qinling subspecies. The giant panda has many species-specific characteristics, including comparatively small organs for body size, small genitalia of male individuals, and low reproduction. Here, we report the most contiguous, high-quality chromosome-level genomes of two extant giant panda subspecies to date, with the first genome assembly of the Qinling subspecies. Compared with the previously assembled giant panda genomes based on short reads, our two assembled genomes increased contiguity over 200-fold at the contig level. Additional sequencing of 25 individuals dated the divergence of the Sichuan and Qinling subspecies into two distinct clusters from 10,000 to 12,000 years ago. Comparative genomic analyses identified the loss of regulatory elements in the dachshund family transcription factor 2 (DACH2) gene and specific changes in the synaptotagmin 6 (SYT6) gene, which may be responsible for the reduced fertility of the giant panda. Positive selection analysis between the two subspecies indicated that the reproduction-associated IQ motif containing D (IQCD) gene may at least partly explain the different reproduction rates of the two subspecies. Furthermore, several genes in the Hippo pathway exhibited signs of rapid evolution with giant panda-specific variants and divergent regulatory elements, which may contribute to the reduced inner organ sizes of the giant panda.

Multi-omics analysis reveals that natural hibernation is crucial for oocyte maturation in the female Chinese alligator.

BACKGROUND: Hibernation in an appropriate environment not only is important for the survival of hibernators in winter, but also is crucial for breeding in the following season for many hibernating species. However, the genetic and epigenetic mechanism underlying this process remain unclear. In the current study, we performed an integrative multi-omics analysis of gonads collected from Chinese alligators that overwintered in wild cave and artificial warmroom to explore transcriptomic and epigenomic alternations in these organs. RESULTS: The data revealed that in the breeding season, female alligators were more strongly affected in terms of gene expression than males by non-hibernation because of overwintering in a warm room, especially for genes related to oocyte maturation, and this effect commenced in winter with the downregulation of STAR, which is the rate limiting factor of steroid biosynthesis. Further, miRNAs were found to play essential roles in this negative effect of overwintering in the warm room on hibernation. The upregulated miRNAs likely were responsible for the suppression of oocyte maturation in the breeding season. Finally, DNA methylome changes, especially hypomethylation, were found to play an important role in the alterations in ovarian function-related gene expression induced by non-hibernation. CONCLUSIONS: Our study revealed the crucial role of hibernation quality for oocyte maturation in the Chinese alligator and the underlying genetic and epigenetic mechanisms, and highlights the importance of habitat, and especially, the overwintering site, in the conservation of not only the Chinese alligator, but also other endangered hibernators.

A Unique Energy-Saving Strategy during Hibernation Revealed by Multi-Omics Analysis in the Chinese Alligator.

Many ectotherms hibernate in face of the harsh winter conditions to improve their survival rate. However, the molecular mechanism underlying this process remains unclear. Here, we explored the hibernation mechanism of Chinese alligator using integrative multi-omics analysis. We revealed that (1) the thyroid hormone biosynthesis, nutrition absorption and metabolism, muscle contraction, urinary excretion and immunity function pathways are overall downregulated during hibernation; (2) the fat catabolism is completely suppressed, contrasting with the upregulation of hepatic fatty-acid-transporter CPT1A, suggesting a unique energy-saving strategy that differs from that in hibernating mammals; (3) the hibernation-related genes are not only directly regulated by DNA methylation but also controlled by methylation-dependent transcription networks. In addition, we identified and compared tissue-specific, species-specific, and conserved season-biased miRNAs, demonstrating complex post-transcriptional regulation during hibernation. Our study revealed the genetic and epigenetic mechanisms underlying hibernation in the Chinese alligator and provided molecular insights into the evolution of hibernation regulation.

Metabolic reprogramming-associated genes predict overall survival for rectal cancer.

Metabolic reprogramming has become a hot topic recently in the regulation of tumour biology. Although hundreds of altered metabolic genes have been reported to be associated with tumour development and progression, the important prognostic role of these metabolic genes remains unknown. We downloaded messenger RNA expression profiles and clinicopathological data from The Cancer Genome Atlas and the Gene Expression Omnibus database to uncover the prognostic role of these metabolic genes. Univariate Cox regression analysis and lasso Cox regression model were utilized in this study to screen prognostic associated metabolic genes. Patients with high-risk demonstrated significantly poorer survival outcomes than patients with low-risk in the TCGA database. Also, patients with high-risk still showed significantly poorer survival outcomes than patients with low-risk in the GEO database. What is more, gene set enrichment analyses were performed in this study to uncover significantly enriched GO terms and pathways in order to help identify potential underlying mechanisms. Our study identified some survival-related metabolic genes for rectal cancer prognosis prediction. These genes might play essential roles in the regulation of metabolic microenvironment and in providing significant potential biomarkers in metabolic treatment.

IDSSR: An Efficient Pipeline for Identifying Polymorphic Microsatellites from a Single Genome Sequence.

Simple sequence repeats (SSRs) are known as microsatellites, and consist of tandem 1-6-base motifs. They have become one of the most popular molecular markers, and are widely used in molecular ecology, conservation biology, molecular breeding, and many other fields. Previously reported methods identify monomorphic and polymorphic SSRs and determine the polymorphic SSRs via experimental validation, which is potentially time-consuming and costly. Herein, we present a new strategy named insertion/deletion (INDEL) SSR (IDSSR) to identify polymorphic SSRs by integrating SSRs with nucleotide insertions/deletions (INDEL) solely based on a single genome sequence and the sequenced pair-end reads. These INDEL indexes and polymorphic SSRs were identified, as well as the number of repeats, repeat motifs, chromosome location, annealing temperature, and primer sequences, enabling future experimental approaches to determine the correctness and polymorphism. Experimental validation with the giant panda demonstrated that our method has high reliability and stability. The efficient SSR pipeline would help researchers obtain high-quality genetic markers for plants and animals of interest, save labor, and reduce costly marker-screening experiments. IDSSR is freely available at https://github.com/Allsummerking/IDSSR.

Characteristics and health risk assessment of heavy metals exposure via household dust from urban area in Chengdu, China.

To investigate the characteristics of heavy metals (Cr, Cd, Pb, Zn, Cu and Ni) in household dust in urban household environment of Chengdu, China, 90 household dust samples were collected from 6 districts of the city. The information of houses and residents were also recorded during dust sampling to identify the correlations between heavy metals in household dust and the house attributes. And also the principal component analysis and cluster analysis for sources and impactor factors. The concentrations of Pb (123mg·kg-1), Zn (675mg·kg-1), Cu (190mg·kg-1), Cr (82.7mg·kg-1), Cd (2.37mg·kg-1) and Ni (52.6mg·kg-1) in household dust are in low or moderate levels when compare with that from other counties or areas. The heavy metals of household dust samples from Chengdu is higher concentrations than that in the street dust from Chengdu, except for Cr. Statistical analysis result showed traffic sources and corrosion of alloys are important factors contributing to the rise concentrations of heavy metals in household dust. In addition, there is negative correlation (p<0.05) between the heavy metals concentrations and floor levels. The ingestion is the important pathway for Pb, Zn, Cu and Ni via household dust exposure to the residents, and the dermal contact was identified as a main route for Cr and Cd in household dust exposure to the residents. There are minor non-carcinogenic and carcinogenic risks from the heavy metals in household dust for the residents in Chengdu.

Pollution characteristics and risk assessment of human exposure to oral bioaccessibility of heavy metals via urban street dusts from different functional areas in Chengdu, China.

Urban street dusts were collected in commercial area (CA), traffic area (TA), educational area (EA), residential area (RA) and parks area (PA) of Chengdu, China, to investigate the concentrations of heavy metals (Pb, Zn, Cu, Ni, Cd and Cr), and analyzed to evaluated possible sources and health risk assessment. The average concentrations (mg/kg) of Pb (82.3), Zn (296), Cu (100), Cd (1.66) and Cr (84.3) in urban street dusts were all higher than the local soil background values. The concentrations of heavy metals in each functional area could be classified as follows: CA>TA>RA>EA>PA. Principal component analysis and Cluster analysis showed mainly derived from the mixed sources of nature and traffic (51.7%). The results of health risk assessment showed no non-carcinogenic and carcinogenic risks of the metals for inhabitants. However, higher concentrations and oral bioaccessibility of the heavy metals in the dusts from CA and TA, indicating there was more health risks to the inhabitants in than that in other functional areas.

Differential diagnosis of pancreatic cancer by single-shot echo-planar imaging diffusion-weighted imaging.

AIM: To investigate the diagnostic ability of single-shot echo-planar imaging (EPI) diffusion-weighted imaging (DWI) to differentiate between malignant and benign pancreatic lesions. METHODS: A computerized search was performed on PubMed, MEDLINE and EMBASE up to August 2014. Nine studies (10 sets of data) with a total of 304 malignant pancreatic lesions and 188 benign pancreatic lesions were included. The characteristics of each study included the study name, year of publication, magnetic resonance modalities used, patient population, strength of field, pulse time, repetition time, echo time (TE), maximum b factor, mean age, mean body weight, fat suppression, number of benign and malignant lesions, and true positive, true negative, false positive and false negative results. All analyses were performed using Meta-DiSc and Stata 11.0. RESULTS: The pooled sensitivity and specificity of single-shot EPI DWI were 0.83 (95%CI: 0.79-0.87) and 0.77 (95%CI: 0.70-0.83), respectively. The positive likelihood ratio and negative likelihood ratio were 5.09 (95%CI: 2.19-11.84) and 0.23 (95%CI: 0.15-0.36), respectively. The P value for the χ(2) heterogeneity for all pooled estimates was < 0.05. From the fitted summary receiver operating characteristic curve, the area under the curve and Q* index were 0.89 and 0.82, respectively. Publication bias was not present (t = 0.58, P = 0.58). Meta-regression analysis indicated that fat suppression, mean age, TE, and maximum b factor were not sources of heterogeneity (all P > 0.05). CONCLUSION: Single-shot EPI DWI is useful to differentiate between malignant and benign pancreatic lesions. Lesion size ≥ 2 cm is the limit for the diagnosis of early lesions.

Sodium hydrosulfide relieves neuropathic pain in chronic constriction injured rats.

Aberrant neuronal activity in injured peripheral nerves is believed to be an important factor in the development of neuropathic pain (NPP). Channel protein pCREB of that activity has been shown to mitigate the onset of associated molecular events in the nervous system, and sodium hydrosulfide (NaHS) could inhibit the expression of pCREB. However, whether NaHS could relieve the pain, it needs further experimental research. Furthermore, the clinical potential that NaHS was used to relieve pain was limited so it would be required. To address these issues, the rats of sciatic nerve chronic constriction injury (CCI) were given intraperitoneal injection of NaHS containing hydrogen sulfide (H2S). The experimental results showed that NaHS inhibited the reduction of paw withdrawal thermal latency (PWTL), mechanical withdrawal threshold (MWT), and the level of pCREB in CCI rats in a dose-dependent manner and they were greatly decreased in NaHSM group (P < 0.05). NaHS alleviates chronic neuropathic pain by inhibiting expression of pCREB in the spinal cord of Sprague-Dawley rats.

Transcriptomic profiling of Aspergillus flavus in response to 5-azacytidine.

Aspergillus flavus is a common saprophyte and opportunistic pathogen producing aflatoxin (AF) and many other secondary metabolites. 5-Azacytidine (5-AC), a derivative of the nucleoside cytidine, is widely used for studies in epigenetics and cancer biology as an inactivator of DNA methyltransferase and is also used for studying secondary metabolism in fungi. Our previous studies showed that 5-AC affects development and inhibits AF production in A. flavus, and that A. flavus lacks DNA methylation. In this study, an RNA-Seq approach was applied to explore the mechanism of 5-AC's effect on A. flavus. We identified 240 significantly differentially expressed (Q-value<0.05) genes after 5-AC treatment, including two backbone genes respectively in secondary metabolite clusters #27 and #35. These two clusters are involved in development or survival of sclerotia. GO functional enrichment analysis showed that these significantly differentially expressed genes were mainly involved in catalytic activity and proteolytic functions. The expressed transcripts of most genes in the AF biosynthetic gene cluster in A. flavus showed no significant changes after treatment with 5-AC and were expressed at low levels, and the transcription regulator genes aflR and aflS in this cluster did not show differential expression relative to the sample without 5-AC treatment. We found that the veA gene, which encodes protein bridges VelB and LaeA, decreased profoundly the expressed transcripts, and brlA, which encodes an early regulator of development, increased its transcripts in A. flavus after 5-AC treatment. Our data support a model whereby 5-AC affects development through increasing the expression of brlA by depressing the expression of veA and AF production through suppressing veA expression and dysregulating carboxypeptidase activity, which then prevents the aflatoxisomes (vesicles) from performing their normal function in AF formation. Furthermore, the suppressed veA expression weakens or even interrupts the connection between VelB and LaeA, leading to dysregulation of the expression pattern of genes involved in development and secondary metabolism in A. flavus. The RNA-seq data presented in this work were also served to improve the annotation of the A. flavus genome. This work provides a comprehensive view of the transcriptome of A. flavus responsive to 5-AC and supports the conclusion that fungal development and secondary metabolism are co-regulated.