Eucommia ulmoides, also called hardy rubber tree, is an economically important tree; however, the lack of its genome sequence restricts the fundamental biological research and applied studies of this plant species. He...Eucommia ulmoides, also called hardy rubber tree, is an economically important tree; however, the lack of its genome sequence restricts the fundamental biological research and applied studies of this plant species. Here, we present a high-quality assembly of its ~l.2-Gb genome （scaffold N50 = 1.88 Mb） with at least 26 723 predicted genes for E. ulmoides, the first sequenced genome of the order Garryales, which was obtained using an integrated strategy combining Illumina sequencing, PacBio sequencing, and BioNano mapping. As a sister taxon to lamiids and campanulids, E. ulmoides underwent an ancient genome triplication shared by core eudicots but no further whole-genome duplication in the last ~125 million years. E. ulmoides exhibits high expression levels and/or gene number expansion for multiple genes involved in stress responses and the biosynthesis of secondary metabolites, which may account for its considerable environmental adaptability. In contrast to the rubber tree （Hevea brasiliensis）, which produces cis-polyisoprene, E. ulmoides has evolved to synthe- size long-chain trans-polyisoprene via farnesyl diphosphate synthases （FPSs）. Moreover, FPS and rub- ber elongation factor/small rubber particle protein gene families were expanded independently from the H. brasiliensis lineage. These results provide new insights into the biology of E. ulmoides and the origin of polyisoprene biosynthesis.展开更多
RNA interfering therapy has emerged as a promising therapeutic modality to treat cancer.The specific and efficient delivery of RNA into a tumor is crucial for achieving effective cancer gene therapy but remains a huge...RNA interfering therapy has emerged as a promising therapeutic modality to treat cancer.The specific and efficient delivery of RNA into a tumor is crucial for achieving effective cancer gene therapy but remains a huge challenge.Herein,we report a novel furin-responsive small interfering RNA(siRNA)delivery vehicle with multiple functions for colorectal tumor treatment.A peptide-based siRNA delivery vehicle RVRR-P18-Gd,consisting of furin enzyme-specific peptide substrate Arg-Val-Arg-Arg(RVRR)with positive charge for siRNA binding,a Gd(III)chelated 1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid(DOTA)(DOTA-Gd)for magnetic resonance imaging,and purpurin 18 as photosensitizer for photodynamic therapy(PDT),was rationally designed and synthesized.Taking advantage of the cationic amphiphilic feature,RVRR-P18-Gd molecules spontaneously self-assembled with negatively charged Hif-1αsiRNA into stable nanoparticles via attractive electrostatic interaction,which effectively prevented siRNA degradation by nucleases,prolonged the circulation half-life,and enhanced tumor accumulation.Moreover,the specific release of Hif-1αsiRNA mediated by endogenous furin significantly downregulated Hif-1αexpression in colorectal cancer cells,resulting in enhanced therapeutic susceptibility,and with the PDT effect,effectively suppressed HCT116 tumor growth in living mice.This work highlights a powerful and universal approach to precisely deliver siRNA to targeted tumors for efficient synergistic therapy.展开更多
We conducted a prospective study to assess the non-inferiority of adjuvant chemotherapy alone versus adjuvant concurrent chemoradiotherapy (CCRT) as an alternative strategy for patients with early-stage (FIGO 2009 sta...We conducted a prospective study to assess the non-inferiority of adjuvant chemotherapy alone versus adjuvant concurrent chemoradiotherapy (CCRT) as an alternative strategy for patients with early-stage (FIGO 2009 stage IB–IIA) cervical cancer having risk factors after surgery. The condition was assessed in terms of prognosis, adverse effects, and quality of life. This randomized trial involved nine centers across China. Eligible patients were randomized to receive adjuvant chemotherapy or CCRT after surgery. The primary end-point was progression-free survival (PFS). From December 2012 to December 2014, 337 patients were subjected to randomization. Final analysis included 329 patients, including 165 in the adjuvant chemotherapy group and 164 in the adjuvant CCRT group. The median follow-up was 72.1 months. The three-year PFS rates were both 91.9%, and the five-year OS was 90.6% versus 90.0% in adjuvant chemotherapy and CCRT groups, respectively. No significant differences were observed in the PFS or OS between groups. The adjusted HR for PFS was 0.854 (95% confidence interval 0.415–1.757;P = 0.667) favoring adjuvant chemotherapy, excluding the predefined non-inferiority boundary of 1.9. The chemotherapy group showed a tendency toward good quality of life. In comparison with post-operative adjuvant CCRT, adjuvant chemotherapy treatment showed non-inferior efficacy in patients with early-stage cervical cancer having pathological risk factors. Adjuvant chemotherapy alone is a favorable alternative post-operative treatment.展开更多
文摘Eucommia ulmoides, also called hardy rubber tree, is an economically important tree; however, the lack of its genome sequence restricts the fundamental biological research and applied studies of this plant species. Here, we present a high-quality assembly of its ~l.2-Gb genome （scaffold N50 = 1.88 Mb） with at least 26 723 predicted genes for E. ulmoides, the first sequenced genome of the order Garryales, which was obtained using an integrated strategy combining Illumina sequencing, PacBio sequencing, and BioNano mapping. As a sister taxon to lamiids and campanulids, E. ulmoides underwent an ancient genome triplication shared by core eudicots but no further whole-genome duplication in the last ~125 million years. E. ulmoides exhibits high expression levels and/or gene number expansion for multiple genes involved in stress responses and the biosynthesis of secondary metabolites, which may account for its considerable environmental adaptability. In contrast to the rubber tree （Hevea brasiliensis）, which produces cis-polyisoprene, E. ulmoides has evolved to synthe- size long-chain trans-polyisoprene via farnesyl diphosphate synthases （FPSs）. Moreover, FPS and rub- ber elongation factor/small rubber particle protein gene families were expanded independently from the H. brasiliensis lineage. These results provide new insights into the biology of E. ulmoides and the origin of polyisoprene biosynthesis.
基金the National Science Foundation of China(grant no.22077092)the Open Project Program of the State Key Laboratory of Radiation Medicine and Protection(grant no.GZK1202140)+2 种基金Science and Technology Development Plan of Suzhou(grant no.SLJ2022018)Scientific Research Project of Suzhou Commission of Health(grant no.GSWS2020028)a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘RNA interfering therapy has emerged as a promising therapeutic modality to treat cancer.The specific and efficient delivery of RNA into a tumor is crucial for achieving effective cancer gene therapy but remains a huge challenge.Herein,we report a novel furin-responsive small interfering RNA(siRNA)delivery vehicle with multiple functions for colorectal tumor treatment.A peptide-based siRNA delivery vehicle RVRR-P18-Gd,consisting of furin enzyme-specific peptide substrate Arg-Val-Arg-Arg(RVRR)with positive charge for siRNA binding,a Gd(III)chelated 1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid(DOTA)(DOTA-Gd)for magnetic resonance imaging,and purpurin 18 as photosensitizer for photodynamic therapy(PDT),was rationally designed and synthesized.Taking advantage of the cationic amphiphilic feature,RVRR-P18-Gd molecules spontaneously self-assembled with negatively charged Hif-1αsiRNA into stable nanoparticles via attractive electrostatic interaction,which effectively prevented siRNA degradation by nucleases,prolonged the circulation half-life,and enhanced tumor accumulation.Moreover,the specific release of Hif-1αsiRNA mediated by endogenous furin significantly downregulated Hif-1αexpression in colorectal cancer cells,resulting in enhanced therapeutic susceptibility,and with the PDT effect,effectively suppressed HCT116 tumor growth in living mice.This work highlights a powerful and universal approach to precisely deliver siRNA to targeted tumors for efficient synergistic therapy.
基金National Natural Science Foundation of China (Nos. 81630060, 81230038, 81372805, and 81472444)National Key Research & Development Program of China (No. 2016YFC0902900)Bristol-Myers Squibb CA139-702 and the National Science-technology Supporting Plan Projects (No.2015BAI13B05).
文摘We conducted a prospective study to assess the non-inferiority of adjuvant chemotherapy alone versus adjuvant concurrent chemoradiotherapy (CCRT) as an alternative strategy for patients with early-stage (FIGO 2009 stage IB–IIA) cervical cancer having risk factors after surgery. The condition was assessed in terms of prognosis, adverse effects, and quality of life. This randomized trial involved nine centers across China. Eligible patients were randomized to receive adjuvant chemotherapy or CCRT after surgery. The primary end-point was progression-free survival (PFS). From December 2012 to December 2014, 337 patients were subjected to randomization. Final analysis included 329 patients, including 165 in the adjuvant chemotherapy group and 164 in the adjuvant CCRT group. The median follow-up was 72.1 months. The three-year PFS rates were both 91.9%, and the five-year OS was 90.6% versus 90.0% in adjuvant chemotherapy and CCRT groups, respectively. No significant differences were observed in the PFS or OS between groups. The adjusted HR for PFS was 0.854 (95% confidence interval 0.415–1.757;P = 0.667) favoring adjuvant chemotherapy, excluding the predefined non-inferiority boundary of 1.9. The chemotherapy group showed a tendency toward good quality of life. In comparison with post-operative adjuvant CCRT, adjuvant chemotherapy treatment showed non-inferior efficacy in patients with early-stage cervical cancer having pathological risk factors. Adjuvant chemotherapy alone is a favorable alternative post-operative treatment.
