TRANSPARENT TESTA 16 collaborates with the MYB-bHLH-WD40 transcriptional complex to produce brown fiber cotton.

Naturally colored cotton (NCC; Gossypium spp.) does not require additional chemical dyeing and is an environmentally friendly textile material with great research potential and applications. Our previous study using linkage and association mapping identified TRANSPARENT TESTA 2 (Gh_TT2) as acting on the proanthocyanin synthesis pathway. However, limited information is available about the genetic regulatory network of NCC. Here, we verified the effectiveness of Gh_TT2 and the roles of Gh_TT2 and red foliated mutant gene (Re) in pigment formation and deposition of brown fiber cotton (BFC). Variations in Gh_TT2 derived from interspecific hybridization between Gossypium barbadense acc. Pima 90-53 and Gossypium hirsutum acc. Handan208 resulted in gene expression differences, thereby causing phenotypic variation. Additionally, the MYB-bHLH-WD complex was found to be negatively modulated by TRANSPARENT TESTA 16/ARABIDOPSIS BSISTER (TT16/ABS). RNA-seq suggested that differential expression of homologous genes of key enzymes in the proanthocyanin synthesis pathway strongly contributes to the color rendering of natural dark brown and light brown cotton. Our study proposes a regulatory model in BFC, which will provide theoretical guidance for the genetic improvement of NCC.

Two duplicated gsdf homeologs cooperatively regulate male differentiation by inhibiting cyp19a1a transcription in a hexaploid fish.

Although evolutionary fates and expression patterns of duplicated genes have been extensively investigated, how duplicated genes co-regulate a biological process in polyploids remains largely unknown. Here, we identified two gsdf (gonadal somatic cell-derived factor) homeologous genes (gsdf-A and gsdf-B) in hexaploid gibel carp (Carassius gibelio), wherein each homeolog contained three highly conserved alleles. Interestingly, gsdf-A and gsdf-B transcription were mainly activated by dmrt1-A (dsx- and mab-3-related transcription factor 1) and dmrt1-B, respectively. Loss of either gsdf-A or gsdf-B alone resulted in partial male-to-female sex reversal and loss of both caused complete sex reversal, which could be rescued by a nonsteroidal aromatase inhibitor. Compensatory expression of gsdf-A and gsdf-B was observed in gsdf-B and gsdf-A mutants, respectively. Subsequently, we determined that in tissue culture cells, Gsdf-A and Gsdf-B both interacted with Ncoa5 (nuclear receptor coactivator 5) and blocked Ncoa5 interaction with Rora (retinoic acid-related orphan receptor-alpha) to repress Rora/Ncoa5-induced activation of cyp19a1a (cytochrome P450, family 19, subfamily A, polypeptide 1a). These findings illustrate that Gsdf-A and Gsdf-B can regulate male differentiation by inhibiting cyp19a1a transcription in hexaploid gibel carp and also reveal that Gsdf-A and Gsdf-B can interact with Ncoa5 to suppress cyp19a1a transcription in vitro. This study provides a typical case of cooperative mechanism of duplicated genes in polyploids and also sheds light on the conserved evolution of sex differentiation.

Immunogenicity, safety, and persistence induced by triple- and standard-strength four-dose hepatitis B vaccination regimens in hemodialysis patients: A multicenter, randomized, parallel-controlled trial in Six cities in Shanxi Province.

BACKGROUND: Hemodialysis (HD) patients represent a high-risk group for hepatitis B infection. It is crucial to administer hepatitis B vaccination and stimulate higher and more sustained levels of anti-HBs. Our aim is to enhance the immunogenicity and persistence by implementing high-dose and prolonged hepatitis B vaccine schedule regimen in HD patients. METHODS: We conducted this multicenter, randomized, parallel-controlled trial between July 2020 and February 2023 at 11 hospitals in Shanxi province, China. A total of 504 HD patients were enrolled. All participants randomly allocated in a ratio of 1:1:1 to receive recombinant HBV vaccine of 3 standard doses (20 µg) at 0-1-6 months (IM20×3 group), 4 standard doses at 0-1-2-6 months (IM20×4 group), or 4 triple doses (60 µg) at 0-1-2-6 months (IM60×4 group). RESULTS: The vaccine-elicited antibody response peaked at month 7. The follow-up outcomes ranging from month 7 to 30 revealed that the response rates of anti-HBs decreased from 85.9% (134/156) to 33.0% (33/100) in IM20×3 group, from 92.5% (135/146) to 53.9% (56/104) in IM20×4 group and from 95.4% (145/152) to 57.3% (55/96) in IM60×4 group. The duration of vaccine-induced response with 75% of patients maintained protective antibody were 21.0 months in IM20×3 group, 25.7 months in IM20×4 group (vs. IM20×3 group, P=0.056) and 29.2 months in IM60×4 group (vs. IM20×3 group, P=0.034). All the adverse reactions were mild. CONCLUSIONS: The four-triple-dose hepatitis B vaccination regimens could enhance the immunogenicity and 2-year duration in HD patients.The trial was registered with Clinical Trials.gov, number NCT03962881. https://classic.clinicaltrials.gov/ct2/show/NCT03962881?term=NCT03962881&draw=2&rank=1.

High-resolution sequencing of nine elite upland cotton cultivars uncovers genic variations and breeding improvement targets.

Structural variations (SVs) are critical factors affecting genome evolution and important traits. However, identification results and functional analyses of SVs in upland cotton are rare. Here, based on the genetic relationships, breeding history and cumulative planting area of upland cotton in China, nine predominant cultivars from the past 60 years (1950s-2010s) were selected for long read sequencing to uncover genic variations and breeding improvement targets for this crop. Based on the ZM24 reference genome, 0.88-1.47 × 104 SVs per cultivar were identified, and an SV set was constructed. SVs affected the expression of a large number of genes during fiber elongation, and a transposable element insertion resulted in the glandless phenotype in upland cotton. Six widespread inversions were identified based on nine draft genomes and high-throughput chromosome conformation capture data. Multiple haplotype blocks that were always associated with aggregated SVs were demonstrated to play a pivotal role in the agronomic traits of upland cotton and drove its adaptation to the northern planting region. Exotic introgression was the source of these haplotype blocks and increased the genetic diversity of upland cotton. Our results enrich the genome resources of upland cotton, and the identified SVs will promote genetic and breeding research in cotton.

Visible-Light-Promoted Radical Cascade Cyclization of 2-Vinyl Benzimidazoles: Access to Benzo[4,5]imidazo[1,2-b]isoquinolin- 11(6H)-ones.

A visible-light-enabled photoredox radical cascade cyclization of 2-vinyl benzimidazole derivatives is developed. This chemistry is applicable to a wide range of N-aroyl 2-vinyl benzimidazoles as acceptors, and halo compounds, including alkyl halides, acyl chlorides and sulfonyl chlorides, as radical precursors. The Langlois reagent also serves as an effective partner in this photocatalytic oxidative cascade process. This protocol provides a robust alternative for rendering highly functionalized benzo[4,5]imidazo[1,2-b]isoquinolin-11(6H)-ones.

Core@Double-Shell Engineering of Zn Particles toward Elevated Dielectric Properties: Multiple Polarization Mechanisms in Zn@Znch@PS/PVDF Composites.

Flexible dielectrics with large dielectric constant (ε') coupled with low loss are highly pursued in many applications. To bolster the ε' of raw Zn (zinc)/poly(vinylidene fluoride, PVDF) while maintaining pimping dielectric loss, in this study, the core@double-shell structured Zn@zinc carbonate (ZnCH)@polystyrene (PS) particles are first synthesized through a suspension polymerization of styrene, and then composited with PVDF to elevate the ε' and keep low loss of the composites. By optimizing the PS shells' thickness and tailoring the electrical resistivity of Zn@ZnCH@PS particles, both the slow inter-particle polarization and fast intra-particle polarization in the composites can be decoupled and synergistically tuned, thus, the Zn@ZnCH@PS/PVDF achieves a much higher ε' and lower dielectric loss, simultaneously, which far exceed the unmodified Zn/PVDF. Both experiment and theoretic calculation reveal that the double-shell ZnCH@PS not only induces and promotes multiple polarizations enhancing the composites' ε', especially at the optimized PS's thickness, but also maintains suppressed loss and conductivity thanks to their obvious barrier effect on long-range charge migration. The core@double-shell filler design strategy facilitates the development of polymer composites with desirable dielectric properties for applications in electronic and electrical power systems.

Genomic anatomy of male-specific microchromosomes in a gynogenetic fish.

Unisexual taxa are commonly considered short-lived as the absence of meiotic recombination is supposed to accumulate deleterious mutations and hinder the creation of genetic diversity. However, the gynogenetic gibel carp (Carassius gibelio) with high genetic diversity and wide ecological distribution has outlived its predicted extinction time of a strict unisexual reproduction population. Unlike other unisexual vertebrates, males associated with supernumerary microchromosomes have been observed in gibel carp, which provides a unique system to explore the rationales underlying male occurrence in unisexual lineage and evolution of unisexual reproduction. Here, we identified a massively expanded satellite DNA cluster on microchromosomes of hexaploid gibel carp via comparing with the ancestral tetraploid crucian carp (Carassius auratus). Based on the satellite cluster, we developed a method for single chromosomal fluorescence microdissection and isolated three male-specific microchromosomes in a male metaphase cell. Genomic anatomy revealed that these male-specific microchromosomes contained homologous sequences of autosomes and abundant repetitive elements. Significantly, several potential male-specific genes with transcriptional activity were identified, among which four and five genes displayed male-specific and male-biased expression in gonads, respectively, during the developmental period of sex determination. Therefore, the male-specific microchromosomes resembling common features of sex chromosomes may be the main driving force for male occurrence in gynogenetic gibel carp, which sheds new light on the evolution of unisexual reproduction.

Covalent organic frameworks and related innovative materials in chiral separation and recognition.

Chiral recognition and enantioseparation are of paramount importance in various fields, including pharmaceuticals, agrochemicals, and material science. Covalent organic frameworks (COFs) have emerged as promising materials for chiral separation due to their unique structural features and tunable properties. This review provided a comprehensive overview of recent progress in the application of COFs and related innovative materials for chiral separation and recognition. Various strategies were analyzed for the design and synthesis of chiral COFs, including the incorporation of chiral building blocks, post-synthetic modification, and the integration of chiral selectors. The applications of chiral COFs in chromatographic techniques, membrane separations, and other emerging methods were critically evaluated with the emphasis on their advantages and limitations. Additionally, the review summarized the potential of combining COFs with other nanomaterials, such as metal-organic frameworks (MOFs) and nanoparticles, to enhance chiral recognition and separation performance. The fundamental principles and mechanisms of chiral recognition were discussed, highlighting the role of chiral selectors and their interactions with enantiomers. Finally, current challenges and future perspectives in this field were discussed, providing insights into the development of more efficient and versatile chiral separation systems based on COFs and related materials.

Exploring the catalytic diversity of two short-chain dehydrogenases/reductases from Stachybotrys chartarum.

Short-chain dehydrogenase/reductases (SDRs) belong to the NAD(P)(H)-dependent oxidoreductase superfamily, which have various functions of catalyzing oxidation/reduction reactions and have been generally used as powerful biocatalysts in the production of pharmaceuticals. In this study, ScSDR1 and ScSDR2, two new SDRs have been identified and characterized from Stachybotrys chartarum 3.5365. Substrate scope investigation revealed that both of the enzymes possessed the ability to oxidize ß-OH to ketone specifically, and exhibited substrate promiscuity and high stereo-selectivity for efficiently catalyzing the structurally different prochiral ketones to chiral alcohols. These findings not only suggest that ScSDR1 and ScSDR2 might be potent synthetic tools in drug research and development, but also provide good examples for further engineered enzymes with higher efficiency and stereo-selectivity.

Re enhances anthocyanin and proanthocyanidin accumulation to produce red foliated cotton and brown fiber.

Red foliated cotton is a typical dominant mutation trait in upland cotton (Gossypium hirsutum). Although mutants have been described, few responsible genes have been identified and characterized. In this study, we performed map-based cloning of the red foliated mutant gene (Re) derived from the cross between G. hirsutum cv. Emian22 and G. barbadense acc. 3-79. Through expression profiling, metabolic pathway analysis, and sequencing of candidate genes, Re was identified as an MYB113 transcription factor. A repeat sequence variation in the promoter region increased the activity of the promoter, which enhanced the expression of Re. Re expression driven by the 35S promoter produced a red foliated phenotype, as expected. When the gene was driven by a fiber elongation-specific promoter, promoter of α-expansin 2 (PGbEXPA2), Re was specifically expressed in 5- to 10-day post-anthesis fibers rather than in other tissues, resulting in brown mature fibers. Re responded to light through phytochrome-interacting factor 4 and formed a dimer with transparent testa 8, which increased its expression as well as that of anthocyanin synthase and UDP-glucose:flavonoid 3-o-glucosyl transferase, and thus activated the entire anthocyanin metabolism pathway. Our research has identified the red foliated mutant gene in cotton, which paves the way for detailed studies of anthocyanin and proanthocyanidin metabolism and pigment accumulation in cotton and provides an alternative strategy for producing brown fiber.

Radiative transfer model and validation for infrared management optical properties of porous polymer materials incorporating impacts of micro-voids.

In order to characterize the infrared (IR) radiation absorption and/or emission performances of functional porous polymers which claim to have healthcare functions due to IR excitation and emission by processing technologies, a radiative transfer model was constructed based on the principle of IR radiation, the Beer-Lambert law, the Fresnel's formula and Planck's law. The theoretical analysis was conducted for the IR management optical properties of the porous sheet polymer materials, including IR reflection, transmission, absorption and emission behaviours during the dynamic process of IR radiation. A modeling method for characterization and revealing of IR management optical properties and optical and thermal transfer behaviours of the reflection and transmission was then investigated from the structural parameters and the temperature rise characteristics of the porous sheet polymer materials during the dynamic IR radiation process. The model was validated by comparing the predicted values from the radiative transfer model with the measured values from the test results of the validation experiments of eight typical porous sheet polymers in an experimental setup. The model was modified by consideration of the influences of two types of micro-voids defects represented by the porosity of micro structure and the thickness compression ratio. The micro-voids defects factors were added to the structural parameters, and therefore the model was improved and the maximum prediction errors of the transmission and reflection surfaces were mostly less than 10%. The radiative transfer model provides the theoretical fundamentals for the evaluation and guidance of IR management optical performances for new products design, development, fabrication and processing in industrial application of functional porous polymers.

Folic acid supplementation in pregnant women with hepatitis B surface antigen improves infant hepatitis B surface antibody mediated by infant IL-4.

Immunoprophylaxis has not completely eliminated hepatitis B virus (HBV) infection due to hyporesponsiveness to hepatitis B vaccine (HepB). We explored the impact of folic acid supplementation (FAS) in pregnant women with positive hepatitis B surface antigen (HBsAg) on their infant hepatitis B surface antibody (anti-HBs) and the mediation effect of infant interleukin-4 (IL-4). We recruited HBsAg-positive mothers and their neonates at baseline. Maternal FAS was obtained via a questionnaire, and neonatal anti-HBs and IL-4 were detected. Follow-up was performed at 11-13 months of age of infants, when anti-HBs and IL-4 were measured. We applied univariate and multivariate analyses. A mediation effect model was performed to explore the mediating role of IL-4. A total of 399 mother-neonate pairs were enrolled and 195 mother-infant pairs were eligible for this analysis. The infant anti-HBs geometric mean concentrations in the maternal FAS group were significnatly higher than those in the no-FAS group (383·8 mIU/ml, 95 % CI: 294·2 mIU/ml to 500·7 mIU/ml v. 217·0 mIU/ml, 95 % CI: 147·0 mIU/ml to 320·4 mIU/ml, z = -3·2, P = 0·001). Infants born to women who took folic acid (FA) within the first trimester were more likely to have high anti-HBs titres (adjusted ß-value = 194·1, P = 0·003). The fold change in IL-4 from neonates to infants partially mediated the beneficial influence of maternal FAS on infant anti-HBs (24·7 % mediation effect) after adjusting for confounding factors. FAS during the first trimester to HBsAg-positive mothers could facilitate higher anti-HBs levels in infants aged 11-13 months partly by upregulating IL-4 in infants.

Continuous enrichment and trace analysis of tetracyclines in bovine milk using dual-functionalized aqueous biphasic system combined with high-performance liquid chromatography.

Two PPG1000 based temperature-sensitive magnetic ionic liquid were synthesized and characterized. The temperature-sensitive magnetic ionic liquid aqueous biphasic system combined with HPLC was applied for the continuous enrichment and trace analysis of tetracycline antibiotics (TC) in bovine milk for the first time. High enrichment factors were achieved and the detection was highly sensitive. The trace analysis of TC was rapid, free of organic solvent, recyclable and magnetically assisted for phase separation. Under optimum conditions, wide linear ranges of 0.25-300 ng/mL for all TC, high enrichment factors of 217.7-231.4, good precisions with relative standard deviation in the range of 0.74-3.97%, very low limits of detection of 0.031-0.067 ng/mL, limits of quantification of 0.103-0.223 ng/mL, and good recoveries of 94.28-99.76% were acquired for the proposed analytical method. Real milk analysis was satisfactory. This developed analytical method is showing great potential for trace analysis of targeted analytes in foods and drinks.

Genome-Wide Identification of Histone Deacetylases and Their Roles Related with Light Response in Tartary Buckwheat (Fagopyrum tataricum).

Histone deacetylases (HDACs), known as histone acetylation erasers, function crucially in plant growth and development. Although there are abundant reports focusing on HDACs of Arabidopsis and illustrating their important roles, the knowledge of HDAC genes in Tartary buckwheat (Polygonales Polygonaceae Fagopyrum tataricum (L.) Gaertn) is still scarce. In the study, a total of 14 HDAC genes were identified and divided into three main groups: Reduced Potassium Dependency-3/His-52 tone Deacetylase 1 (RPD3/HDA1), Silent Information Regulator 2 (SIR2), and the plant-53 specific HD2. Domain and motif composition analysis showed there were conserved domains and motifs in members from the same subfamilies. The 14 FtHDACs were distributed asymmetrically on 7 chromosomes, with three segmental events and one tandem duplication event identified. The prediction of the cis-element in promoters suggested that FtHDACs probably acted in numerous biological processes including plant growth, development, and response to environmental signals. Furthermore, expression analysis based on RNA-seq data displayed that all FtHDAC genes were universally and distinctly expressed in diverse tissues and fruit development stages. In addition, we found divergent alterations in FtHDACs transcript abundance in response to different light conditions according to RNA-seq and RT-qPCR data, indicating that five FtHDACs might be involved in light response. Our findings could provide fundamental information for the HDAC gene family and supply several targets for future function analysis of FtHDACs related with light response of Tartary buckwheat.

Total Synthesis of Yuzurine-type Alkaloid Daphgraciline.

The first total synthesis of daphgraciline has been achieved, which also represents the first example of the synthesis of Daphniphyllum yuzurine-type alkaloids (∼50 members). The unique bridged azabicyclo[4.3.1] ring system in the yuzurine-type subfamily was efficiently and diastereoselectively assembled via a mild type II [5+2] cycloaddition for the first time. The compact tetracyclic [6-7-5-5] skeleton was installed efficiently via an intramolecular Diels-Alder reaction, followed by a benzilic acid-type rearrangement. The synthetically challenging spiro tetrahydropyran moiety in the final product was installed diastereoselectively via a TiIII-mediated reductive epoxide coupling reaction. Potential access to enantioenriched daphgraciline is presented.

Changes of serum miR-221 and miR-145 levels with papillary thyroid carcinoma and their relationship with invasive activity.

This study aimed to investigate the expression of miR-221 and miR-145 in papillary thyroid carcinoma, and the effect of miR-221 and miR-145 on the invasion ability of thyroid cancer cells and its mechanism. For this purpose, 120 patients with thyroid nodules were divided into the observation group (PTC) of 43 cases and the control group (benign nodules) of 42 cases according to postoperative pathological diagnosis. Total RNA was extracted from serum samples of all patients, and the expression levels of miRNA-145 and miR-221 were detected by fluorescence quantitative PCR. The expression of two kinds of miRNAs in the groups was compared, and their correlation was analyzed. The results showed that the expression of miRNA-145 in thyroid cancer tissues was lower than that in paired adjacent normal tissues (P < 0.001). The expression of miRNA-221 in thyroid cancer tissues was higher than that in paired adjacent normal tissues (P < 0.001). The proliferation and migration ability of miRNA-145 cells were significantly decreased (P < 0.01). The expression of miRNA-221 was up-regulated, and the proliferation and migration ability of cells was significantly enhanced (P < 0.05). High expression of miRNA-145 can inhibit cell proliferation and migration and promote apoptosis, while high expression of miRNA-221 will promote cell proliferation and migration and enhance the invasion ability of cancer cells. In general, the expression of miRNA-22l in serum of PTC patients is significantly up-regulated, while the expression level of miR-145 is down-regulated, which can be used as effective indicators to judge the biological activity of the tumor, and the combined detection of the two can significantly enhance the diagnostic value of PTC. Upregulation of miR-145 inhibits PTC cell proliferation; arrests cell cycle and promotes apoptosis miR-145 may play an important role as a tumor suppressor gene.

Gossypium tomentosum genome and interspecific ultra-dense genetic maps reveal genomic structures, recombination landscape and flowering depression in cotton.

The high-quality reference-grade genome for Gossupium tomentosum can greatly promote the progress in biological research and introgression breeding for the mainly cultivated species, G. hirsutum. Here, we report a high-quality genome assembly for G. tomentosum by integrating PacBio and Hi-C technologies. Comparative genomic analysis revealed a large number of genetic variations. Two re-sequencing-based ultra-dense genetic maps were constructed which comprised 4,047,199 and 6,009,681 SNPs, 4120 and 4599 bins and covering 4126.36 cM and 4966.72 cM in the EMF2 (F2 from G. hirsutum × G. tomentosum) and GHF2 (F2 from G. hirsutum × G. barbadense). The EMF2 exhibited lower recombination rate at the whole-genome level as compared with GHF2. We mapped 22 and 33 QTL associated with crossover frequency and predicted Gh_MRE11 and Gh_FIGL1 as the candidate genes governing crossover in the EMF2 and GHF2, respectively. We identified 13 significant QTL that regulate the floral transition, and revealed that Gh_AGL18 was associated with the floral transition. Therefore, our study provides a valuable genomic resource to support a better understanding of cotton interspecific cross and recombination landscape for genetic improvement and breeding in cotton.

Unravelling the Polytoxicology of Chlorfenapyr on Non-Target HepG2 Cells: The Involvement of Mitochondria-Mediated Programmed Cell Death and DNA Damage.

Chlorfenapyr (CHL) is a type of insecticide with a wide range of insecticidal activities and unique targets. The extensive use of pesticides has caused an increase in potential risks to the environment and human health. However, the potential toxicity of CHL and its mechanisms of action on humans remain unclear. Therefore, human liver cells (HepG2) were used to investigate the cytotoxic effect and mechanism of toxicity of CHL at the cellular level. The results showed that CHL induced cellular toxicity in HepG2 cells and induced mitochondrial damage associated with reactive oxygen species (ROS) accumulation and mitochondrial calcium overload, ultimately leading to apoptosis and autophagy in HepG2 cells. Typical apoptotic changes occurred, including a decline in the mitochondrial membrane potential, the promotion of Bax/Bcl-2 expression causing the release of cyt-c into the cytosol, the activation of cas-9/-3, and the cleavage of PARP. The autophagic effects included the formation of autophagic vacuoles, accumulation of Beclin-1, transformation of LC3-II, and downregulation of p62. Additionally, DNA damage and cell cycle arrest were detected in CHL-treated cells. These results show that CHL induced cytotoxicity associated with mitochondria-mediated programmed cell death (PCD) and DNA damage in HepG2 cells.

[Study on the Fixation Effect of Plate in the Middle Tibial Fracture Based on Finite Element Analysis].

In this study, tibial shaft fracture has been treated with implants as numerically to investigate the stress behavior and the effect of plate material, position and length under pressure load. Plates of stainless steel, titanium alloy(Ti6Al4V), or CF-PEEK(CF50) were used to fix the tibial shaft comminuted fracture in different location and different working length. The maximum stress, the maximum micromotion of fracture and the stress shielding of cortex bone were analyzed. CF50 is more ideal biomechanical fixation material than traditional metal material for the treatment of tibial shaft comminuted fractures. In the treatment of tibial shaft comminuted fracture, lateral position and with relatively long working length of the plate have the advantages in micromotion, stress and stress shielding rate of the fracture end.

Profibrotic mechanisms of DPP8 and DPP9 highly expressed in the proximal renal tubule epithelial cells.

BACKGROUND: DPP8 and DPP9 have been demonstrated to play important roles in multiple diseases. Evidence for increased gene expression of DPP8 and DPP9 in tubulointerstitium was found to be associated with the decline of kidney function in chronic kidney disease (CKD) patients, which was observed in the Nephroseq human database. To examine the role of DPP8 and DPP9 in the tubulointerstitial injury, we determined the efficacy of DPP8 and DPP9 on epithelial-to-mesenchymal transition (EMT) and tubulointerstitial fibrosis (TIF) as well as the underlying mechanisms. METHODS: We conducted the immunofluorescence of DPP8 and DPP9 in kidney biopsy specimens of CKD patients, established unilateral ureteral obstruction (UUO) animal model, treated with TC-E5007 (a specific inhibitor of both DPP8 and DPP9) or Saxagliptin (positive control) or saline, and HK-2 cells model. RESULTS: We observed the significantly increased expression of DPP8 and DPP9 in the renal proximal tubule epithelial cells of CKD patients compared to the healthy control subjects. DPP8/DPP9 inhibitor TC-E5007 could significantly attenuate the EMT and extracellular matrix (ECM) synthesis in UUO mice, all these effects were mediated via interfering with the TGF-ß1/Smad signaling. TC-E5007 treatment also presented reduced renal inflammation and improved renal function in the UUO mice compared to the placebo-treated UUO group. Furthermore, the siRNA for DPP8 and DPP9, and TC-E5007 treatment decreased EMT- and ECM-related proteins in TGF-ß1-treated HK-2 cells respectively, which could be reversed significantly by transduction with lentivirus-DPP8 and lentivirus-DPP9. CONCLUSION: These data obtained provide evidence that the DPP8 and DPP9 could be potential therapeutic targets against TIF.