SUMMARYPlant life is characterized by major phase changes. We studied the role of histone deacetylase (HDAC) activity in the transition from seed to seedling in Arabidopsis. Pharmacological inhibition of HDAC stimulated germination of freshly harvested seeds. Subsequent analysis revealed that histone deacetylase 9 (hda9) mutant alleles displayed reduced seed dormancy and faster germination than wild-type plants. Transcriptome meta-analysis comparisons between the hda9 dry seed transcriptome and published datasets demonstrated that transcripts of genes that are induced during imbibition in wild-type prematurely accumulated in hda9-1 dry seeds. This included several genes associated with photosynthesis and photoautotrophic growth such as RuBisCO and RuBisCO activase (RCA). Chromatin immunoprecipitation experiments demonstrated enhanced histone acetylation levels at their loci in young hda9-1 seedlings. Our observations suggest that HDA9 negatively influences germination and is involved in the suppression of seedling traits in dry seeds, probably by transcriptional repression via histone deacetylation. Accordingly, HDA9 transcript is abundant in dry seeds and becomes reduced during imbibition in wild-type seeds. The proposed function of HDA9 is opposite to that of its homologous genes HDA6 and HDA19, which have been reported to repress embryonic properties in germinated seedlings.
BackgroundOSCC is one of the most common malignancies and numerous clinical agents currently applied in combinative chemotherapy. Here we reported a novel therapeutic strategy, SAHA and DDP-loaded PECE (SAHA-DDP/PECE), can improve the therapeutic effects of intratumorally chemotherapy on OSCC cell xenografts.Objective/PurposeThe objective of this study was to evaluate the therapeutic efficacy of the SAHA-DDP/PECE in situ controlled drug delivery system on OSCC cell xenografts.MethodsA biodegradable and thermosensitive hydrogel was successfully developed to load SAHA and DDP. Tumor-beared mice were intratumorally administered with SAHA-DDP/PECE at 50 mg/kg (SAHA) +2 mg/kg (DDP) in 100 ul PECE hydrogel every two weeks, SAHA-DDP at 50 mg/kg(SAHA) +2 mg/kg(DDP) in NS, 2 mg/kg DDP solution, 50 mg/kg SAHA solution, equal volume of PECE hydrogel, or equal volume of NS on the same schedule, respectively. The antineoplastic actions of SAHA and DDP alone and in combination were evaluated using the determination of tumor volume, immunohistochemistry, western blot, and TUNEL analysis.ResultsThe hydrogel system was a free-flowing sol at 10°C, become gel at body temperature, and could sustain more than 14 days in situ. SAHA-DDP/PECE was subsequently injected into tumor OSCC tumor-beared mice. The results demonstrated that such a strategy as this allows the carrier system to show a sustained release of SAHA and DDP in vivo, and could improved therapeutic effects compared with a simple additive therapeutic effect of SAHA and DDP on mouse model.ConclusionsOur research indicated that the novel SAHA-DDP/PECE system based on biodegradable PECE copolymer enhanced the therapeutic effects and could diminished the side effects of SAHA/DDP. The present work might be of great importance to the further exploration of the potential application of SAHA/DDP-hydrogel controlled drug release system in the treatment of OSCC.
Background/Aims: The impact of early peritonitis on the outcome of elderly peritoneal dialysis (PD) patients has not been studied. We aimed to research the influence of early peritonitis on patient outcomes in elderly PD patients. Methods: This study involved elderly PD patients (age ≥65) who underwent PD between Jan 1, 2004 and Jul 31, 2013. Patient characteristics were collected in our database. Early peritonitis was defined as peritonitis within 6 months after the initiation of PD. Patient survival and technique were compared among the non-peritonitis, early peritonitis and late peritonitis groups using Cox regression analysis. Results: There were 155 subjects involved in this study. The patients were divided among a non-peritonitis group (n=78), early peritonitis group (n=32) and late peritonitis group (n=45). The organisms causing first peritonitis in the two groups did not differ significantly. After adjustment for age, diabetes, serum albumin and residual renal function, multivariable Cox regression model revealed that compared with the early peritonitis group, both the non-peritonitis group (HR 0.57, RI 0.32-0.99, p=0.046) and the late peritonitis group (HR 0.37, RI 0.16-0.75, p=0.004) exhibited a lower patient mortality rate. Conclusions: Early peritonitis is an independent risk factor for mortality in elderly peritoneal dialysis patients.
Objective: To evaluate the accuracy of a deep learning-based auto-segmentation mode to that of manual contouring by one medical resident, where both entities tried to mimic the delineation "habits" of the same clinical senior physician. Methods: This study included 125 cervical cancer patients whose clinical target volumes (CTVs) and organs at risk (OARs) were delineated by the same senior physician. Of these 125 cases, 100 were used for model training and the remaining 25 for model testing. In addition, the medical resident instructed by the senior physician for approximately 8 months delineated the CTVs and OARs for the testing cases. The dice similarity coefficient (DSC) and the Hausdorff Distance (HD) were used to evaluate the delineation accuracy for CTV, bladder, rectum, small intestine, femoral-head-left, and femoral-head-right. Results: The DSC values of the auto-segmentation model and manual contouring by the resident were, respectively, 0.86 and 0.83 for the CTV (P < 0.05), 0.91 and 0.91 for the bladder (P > 0.05), 0.88 and 0.84 for the femoral-head-right (P < 0.05), 0.88 and 0.84 for the femoral-head-left (P < 0.05), 0.86 and 0.81 for the small intestine (P < 0.05), and 0.81 and 0.84 for the rectum (P > 0.05). The HD (mm) values were, respectively, 14.84 and 18.37 for the CTV (P < 0.05), 7.82 and 7.63 for the bladder (P > 0.05), 6.18 and 6.75 for the femoral-head-right (P > 0.05), 6.17 and 6.31 for the femoral-head-left (P > 0.05), 22.21 and 26.70 for the small intestine (P > 0.05), and 7.04 and 6.13 for the rectum (P > 0.05). The auto-segmentation model took approximately 2 min to delineate the CTV and OARs while the resident took approximately 90 min to complete the same task. Conclusion: The auto-segmentation model was as accurate as the medical resident but with much better efficiency in this study. Furthermore, the auto-segmentation approach offers additional perceivable advantages of being consistent and ever improving when compared with manual approaches.
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