Dear Editor Salvia miltiorrhiza Bunge （Danshen） is a medicinal plant of the Lamiaceae family, and its dried roots have long been used in traditional Chinese medicine with hydrophilic phenolic acids and tanshinones a...Dear Editor Salvia miltiorrhiza Bunge （Danshen） is a medicinal plant of the Lamiaceae family, and its dried roots have long been used in traditional Chinese medicine with hydrophilic phenolic acids and tanshinones as pharmaceutically active components （Zhang et al., 2014; Xu et al., 2016）. The first step of tanshinone biosynthesis is bicyclization of the general diterpene precursor （E,E,E）-geranylgeranyl diphosphate （GGPP） to copalyl diphosphate （CPP） by CPP synthases （CPSs）, which is followed by a cyclization or rearrangement reaction catalyzed by kaurene synthase-like enzymes （KSL）. The resulting intermediate is usually an olefin, which requires the insertion of oxygen by cytochrome P450 mono-oxygenases （CYPs） for the final production of diterpenoids （Zi et al., 2014）. While the CPS, KSL, and several early acting CYPs （CYP76AH1, CYP76AH3, and CYP76AK1） for tanshinone biosynthesis have been identified in S. miltiorrhiza （Gao et al., 2009; Guo et al., 2013, 2016; Zi and Peters, 2013）, the majority of the overall biosynthetic pathway, as well as the relevant regulatory factors associated with tanshinone production, remains elusive （Figure 1B）.展开更多
Objective： Stomach and esophageal cancer are imposing huge threats to the health of Chinese people whereasthere were few studies on the financial burden of the two cancers.Methods： Costs per hospitalization of all p...Objective： Stomach and esophageal cancer are imposing huge threats to the health of Chinese people whereasthere were few studies on the financial burden of the two cancers.Methods： Costs per hospitalization of all patients with stomach or esophageal cancer discharged betweenSeptember 2015 and August 2016 in seven cities/counties in China were collected, together with their demographicinformation and clinical details. Former patients in the same hospitals were sampled to collect information onannual direct non-medical cost, indirect costs and annual number of hospitalization. Annual direct medical cost wasobtained by multiplying cost per hospitalization by annual number of hospitalization. Annual cost of illness （ACI）was obtained by adding the average value of annual direct medical cost, direct non-medical cost and indirect cost,stratified by sex, age, clinical stage, therapy and pathologic type in urban and rural areas. Costs per hospitalizationwere itemized into eight parts to calculate the proportion of each part. All costs were converted to 2016 US dollars（1 USD：6.6423 RMB）.Results： Totally 19,986 cases were included, predominately male. Mean ages of stomach cancer and urbanpatients were lower than that of esophageal cancer and rural patients. ACI of stomach and esophageal cancerpatients were $10,449 and $13,029 in urban areas, and $2,927 and $3,504 in rural areas, respectively. Greater ACIwas associated with male, non-elderly patients as well as those who were in stage I and underwent surgeries.Western medicine fee took the largest proportion of cost per hospitalization.Conclusions： The ACI of stomach and esophageal cancer was tremendous and varied substantially among thepopulation in China. Preferential policies of medical insurance should be designed to tackle with this burden andfurther reduce the health care inequalities.展开更多
Tooth is a complex hard tissue organ and consists of multiple cell types that are regulated by important signaling pathways such as Wnt and BMP signaling.Serious injuries and/or loss of tooth or periodontal tissues ma...Tooth is a complex hard tissue organ and consists of multiple cell types that are regulated by important signaling pathways such as Wnt and BMP signaling.Serious injuries and/or loss of tooth or periodontal tissues may significantly impact aesthetic appearance,essential oral functions and the quality of life.Regenerative dentistry holds great promise in treating oral/dental disorders.The past decade has witnessed a rapid expansion of our understanding of the biological features of dental stem cells,along with the signaling mechanisms governing stem cell self-renewal and differentiation.In this review,we first summarize the biological characteristics of seven types of dental stem cells,including dental pulp stem cells,stem cells from apical papilla,stem cells from human exfoliated deciduous teeth,dental follicle precursor cells,periodontal ligament stem cells,alveolar bone-derived mesenchymal stem cells(MSCs),and MSCs from gingiva.We then focus on how these stem cells are regulated by bone morphogenetic protein(BMP)and/or Wnt signaling by examining the interplays between these pathways.Lastly,we analyze the current status of dental tissue engineering strategies that utilize oral/dental stem cells by harnessing the interplays between BMP and Wnt pathways.We also highlight the challenges that must be addressed before the dental stem cells may reach any clinical applications.Thus,we can expect to witness significant progresses to be made in regenerative dentistry in the coming decade.展开更多
Tanshinones are a class of bioactive components in the traditional Chinese medicine Salvia miltiorrhiza, and their biosynthesis and regulation have been widely studied. Current studies show that basic leucine zipper(b...Tanshinones are a class of bioactive components in the traditional Chinese medicine Salvia miltiorrhiza, and their biosynthesis and regulation have been widely studied. Current studies show that basic leucine zipper(bZIP) proteins regulate plant secondary metabolism, growth and developmental processes. However, the b ZIP transcription factors involved in tanshinone biosynthesis are unknown.Here, we conducted the first genome-wide survey of the b ZIP gene family and analyzed the phylogeny,gene structure, additional conserved motifs and alternative splicing events in S. miltiorrhiza. A total of 70 Smb ZIP transcription factors were identified and categorized into 11 subgroups based on their phylogenetic relationships with those in Arabidopsis. Moreover, seventeen Smb ZIP genes underwent alternative splicing events. According to the transcriptomic data, the Smb ZIP genes that were highly expressed in the Danshen root and periderm were selected. Based on the prediction of b ZIP binding sites in the promoters and the co-expression analysis and co-induction patterns in response to Ag^+ treatment via quantitative real-time polymerase chain reaction(qRT-PCR), we concluded that Smb ZIP7 and Smb ZIP20 potentially participate in the regulation of tanshinone biosynthesis. These results provide a foundation for further functional characterization of the candidate Smb ZIP genes, which have the potential to increase tanshinone production.展开更多
Solid-state electrolytes(SSEs)are widely considered the essential components for upcoming rechargeable lithium-ion batteries owing to the potential for great safety and energy density.Among them,polymer solid-state el...Solid-state electrolytes(SSEs)are widely considered the essential components for upcoming rechargeable lithium-ion batteries owing to the potential for great safety and energy density.Among them,polymer solid-state electrolytes(PSEs)are competitive candidates for replacing commercial liquid electrolytes due to their flexibility,shape versatility and easy machinability.Despite the rapid development of PSEs,their practical application still faces obstacles including poor ionic conductivity,narrow electrochemical stable window and inferior mechanical strength.Polymer/inorganic composite electrolytes(PIEs)formed by adding ceramic fillers in PSEs merge the benefits of PSEs and inorganic solid-state electrolytes(ISEs),exhibiting appreciable comprehensive properties due to the abundant interfaces with unique characteristics.Some PIEs are highly compatible with high-voltage cathode and lithium metal anode,which offer desirable access to obtaining lithium metal batteries with high energy density.This review elucidates the current issues and recent advances in PIEs.The performance of PIEs was remarkably influenced by the characteristics of the fillers including type,content,morphology,arrangement and surface groups.We focus on the molecular interaction between different components in the composite environment for designing high-performance PIEs.Finally,the obstacles and opportunities for creating high-performance PIEs are outlined.This review aims to provide some theoretical guidance and direction for the development of PIEs.展开更多
Triptolide（TPL/TL） is a natural drug with novel anticancer effects. Preclinical studies indicated that TPL inhibits cell proliferation, induces cell apoptosis, inhibits tumor metastasis and enhances the effect of ot...Triptolide（TPL/TL） is a natural drug with novel anticancer effects. Preclinical studies indicated that TPL inhibits cell proliferation, induces cell apoptosis, inhibits tumor metastasis and enhances the effect of other therapeutic methods in various cancer cell lines. Multiple molecules and signaling pathways, such as caspases, heat-shock proteins, NF-κB, and deoxyribonucleic acid（DNA） repair-associated factors, are associated with the anti-cancer effect. TPL also improves chemoradiosensitivity in cancer therapy. Phase I trials indicate the potential clinical value of TPL use. However, further trials with larger sample sizes are needed to confirm these results.展开更多
During the whole life cycle of mammals, new neurons are constantly regenerated in the subgranular zone of the dentate gyms and in the subventricular zone of the lateral ventricles. Thanks to emerging methodologies, gr...During the whole life cycle of mammals, new neurons are constantly regenerated in the subgranular zone of the dentate gyms and in the subventricular zone of the lateral ventricles. Thanks to emerging methodologies, great progress has been made in the characterization of spinal cord endogenous neural stem cells （ependymal cells） and identification of their role in adult spinal cord development. As recently evidenced, both the intrinsic and extrinsic molecular mechanisms of ependymal cells control the sequential steps of the adult spinal cord neurogenesis. This review introduces the concept of adult endogenous neurogenesis, the reaction of ependymal cells after adult spinal cord injury （SCI）, the heterogeneity and markers of ependymal cells, the factors that regulate ependymal cells, and the niches that impact the activation or differentiation of ependymal ceils.展开更多
文摘Dear Editor Salvia miltiorrhiza Bunge （Danshen） is a medicinal plant of the Lamiaceae family, and its dried roots have long been used in traditional Chinese medicine with hydrophilic phenolic acids and tanshinones as pharmaceutically active components （Zhang et al., 2014; Xu et al., 2016）. The first step of tanshinone biosynthesis is bicyclization of the general diterpene precursor （E,E,E）-geranylgeranyl diphosphate （GGPP） to copalyl diphosphate （CPP） by CPP synthases （CPSs）, which is followed by a cyclization or rearrangement reaction catalyzed by kaurene synthase-like enzymes （KSL）. The resulting intermediate is usually an olefin, which requires the insertion of oxygen by cytochrome P450 mono-oxygenases （CYPs） for the final production of diterpenoids （Zi et al., 2014）. While the CPS, KSL, and several early acting CYPs （CYP76AH1, CYP76AH3, and CYP76AK1） for tanshinone biosynthesis have been identified in S. miltiorrhiza （Gao et al., 2009; Guo et al., 2013, 2016; Zi and Peters, 2013）, the majority of the overall biosynthetic pathway, as well as the relevant regulatory factors associated with tanshinone production, remains elusive （Figure 1B）.
基金supported by the Special Fund for Health Research in the Public Interest (No. 201502001)
文摘Objective： Stomach and esophageal cancer are imposing huge threats to the health of Chinese people whereasthere were few studies on the financial burden of the two cancers.Methods： Costs per hospitalization of all patients with stomach or esophageal cancer discharged betweenSeptember 2015 and August 2016 in seven cities/counties in China were collected, together with their demographicinformation and clinical details. Former patients in the same hospitals were sampled to collect information onannual direct non-medical cost, indirect costs and annual number of hospitalization. Annual direct medical cost wasobtained by multiplying cost per hospitalization by annual number of hospitalization. Annual cost of illness （ACI）was obtained by adding the average value of annual direct medical cost, direct non-medical cost and indirect cost,stratified by sex, age, clinical stage, therapy and pathologic type in urban and rural areas. Costs per hospitalizationwere itemized into eight parts to calculate the proportion of each part. All costs were converted to 2016 US dollars（1 USD：6.6423 RMB）.Results： Totally 19,986 cases were included, predominately male. Mean ages of stomach cancer and urbanpatients were lower than that of esophageal cancer and rural patients. ACI of stomach and esophageal cancerpatients were $10,449 and $13,029 in urban areas, and $2,927 and $3,504 in rural areas, respectively. Greater ACIwas associated with male, non-elderly patients as well as those who were in stage I and underwent surgeries.Western medicine fee took the largest proportion of cost per hospitalization.Conclusions： The ACI of stomach and esophageal cancer was tremendous and varied substantially among thepopulation in China. Preferential policies of medical insurance should be designed to tackle with this burden andfurther reduce the health care inequalities.
基金The authors apologize to those investigators whose original work was not cited due to space constraints.The authors’research was supported in part by research grants from the National Institutes of Health(AT004418&AR054381 to TCH&HHL)Scoliosis Research Society(MJL&TCH),the 973 Program of Ministry of Science and Technology(MOST)of China(#2011CB707900 to TCH),the National Natural Science Foundation of China(#81400493 to FZ)+2 种基金Chongqing Municipal Commissions on Education(#KJ130303 to JW)Chongqing Municipal Commissions on Science&Technology(#cstc2013jcyjA0093 to JW)Chongqing Municipal Commissions Yubei District Science&Technology(#2014 Society of Human Resource Unit 14 to JW).MKM was a recipient of Howard Hughes Medical Institute Medical Research Fellowship.
文摘Tooth is a complex hard tissue organ and consists of multiple cell types that are regulated by important signaling pathways such as Wnt and BMP signaling.Serious injuries and/or loss of tooth or periodontal tissues may significantly impact aesthetic appearance,essential oral functions and the quality of life.Regenerative dentistry holds great promise in treating oral/dental disorders.The past decade has witnessed a rapid expansion of our understanding of the biological features of dental stem cells,along with the signaling mechanisms governing stem cell self-renewal and differentiation.In this review,we first summarize the biological characteristics of seven types of dental stem cells,including dental pulp stem cells,stem cells from apical papilla,stem cells from human exfoliated deciduous teeth,dental follicle precursor cells,periodontal ligament stem cells,alveolar bone-derived mesenchymal stem cells(MSCs),and MSCs from gingiva.We then focus on how these stem cells are regulated by bone morphogenetic protein(BMP)and/or Wnt signaling by examining the interplays between these pathways.Lastly,we analyze the current status of dental tissue engineering strategies that utilize oral/dental stem cells by harnessing the interplays between BMP and Wnt pathways.We also highlight the challenges that must be addressed before the dental stem cells may reach any clinical applications.Thus,we can expect to witness significant progresses to be made in regenerative dentistry in the coming decade.
基金supported by the National Natural Science Foundation (Grant No.81573398)Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences (CIFMS,2016-I2M-3–016)
文摘Tanshinones are a class of bioactive components in the traditional Chinese medicine Salvia miltiorrhiza, and their biosynthesis and regulation have been widely studied. Current studies show that basic leucine zipper(bZIP) proteins regulate plant secondary metabolism, growth and developmental processes. However, the b ZIP transcription factors involved in tanshinone biosynthesis are unknown.Here, we conducted the first genome-wide survey of the b ZIP gene family and analyzed the phylogeny,gene structure, additional conserved motifs and alternative splicing events in S. miltiorrhiza. A total of 70 Smb ZIP transcription factors were identified and categorized into 11 subgroups based on their phylogenetic relationships with those in Arabidopsis. Moreover, seventeen Smb ZIP genes underwent alternative splicing events. According to the transcriptomic data, the Smb ZIP genes that were highly expressed in the Danshen root and periderm were selected. Based on the prediction of b ZIP binding sites in the promoters and the co-expression analysis and co-induction patterns in response to Ag^+ treatment via quantitative real-time polymerase chain reaction(qRT-PCR), we concluded that Smb ZIP7 and Smb ZIP20 potentially participate in the regulation of tanshinone biosynthesis. These results provide a foundation for further functional characterization of the candidate Smb ZIP genes, which have the potential to increase tanshinone production.
基金the National Natural Science Foundation of China(Nos.22279070,U21A20170 and 22175106)the Ministry of Science and Technology of China(Nos.2019YFA0705703,2021YFB2501900 and 2019YFE0100200)+1 种基金the Tsinghua University Initiative Scientific Research Program(20223080001)the Tsinghua-Foshan Innovation Special Fund(2021THFS0216)。
文摘Solid-state electrolytes(SSEs)are widely considered the essential components for upcoming rechargeable lithium-ion batteries owing to the potential for great safety and energy density.Among them,polymer solid-state electrolytes(PSEs)are competitive candidates for replacing commercial liquid electrolytes due to their flexibility,shape versatility and easy machinability.Despite the rapid development of PSEs,their practical application still faces obstacles including poor ionic conductivity,narrow electrochemical stable window and inferior mechanical strength.Polymer/inorganic composite electrolytes(PIEs)formed by adding ceramic fillers in PSEs merge the benefits of PSEs and inorganic solid-state electrolytes(ISEs),exhibiting appreciable comprehensive properties due to the abundant interfaces with unique characteristics.Some PIEs are highly compatible with high-voltage cathode and lithium metal anode,which offer desirable access to obtaining lithium metal batteries with high energy density.This review elucidates the current issues and recent advances in PIEs.The performance of PIEs was remarkably influenced by the characteristics of the fillers including type,content,morphology,arrangement and surface groups.We focus on the molecular interaction between different components in the composite environment for designing high-performance PIEs.Finally,the obstacles and opportunities for creating high-performance PIEs are outlined.This review aims to provide some theoretical guidance and direction for the development of PIEs.
基金supported by a project funded by the Priority Academic Program Development of Jiangsu HigherEducation Institutions (PAPD) (JX10231801)grants from Key Academic Discipline of Jiangsu Province "Medical Aspects of Specific Environments"
文摘Triptolide（TPL/TL） is a natural drug with novel anticancer effects. Preclinical studies indicated that TPL inhibits cell proliferation, induces cell apoptosis, inhibits tumor metastasis and enhances the effect of other therapeutic methods in various cancer cell lines. Multiple molecules and signaling pathways, such as caspases, heat-shock proteins, NF-κB, and deoxyribonucleic acid（DNA） repair-associated factors, are associated with the anti-cancer effect. TPL also improves chemoradiosensitivity in cancer therapy. Phase I trials indicate the potential clinical value of TPL use. However, further trials with larger sample sizes are needed to confirm these results.
基金supported by the State Key Program of National Natural Science Foundation of China(31130022,31320103903,31271037)the National Science and Technology Pillar Program of China(2012BAI17B04)+2 种基金the International Cooperation in Science and Technology Projects of the Ministry of Science Technology of China(2014DFA30640)the National Ministry of Education Special Fund for Excellent Doctoral Dissertation(201356)the Special Funds for Excellent Doctoral Dissertation of Beijing,China(20111000601)
文摘During the whole life cycle of mammals, new neurons are constantly regenerated in the subgranular zone of the dentate gyms and in the subventricular zone of the lateral ventricles. Thanks to emerging methodologies, great progress has been made in the characterization of spinal cord endogenous neural stem cells （ependymal cells） and identification of their role in adult spinal cord development. As recently evidenced, both the intrinsic and extrinsic molecular mechanisms of ependymal cells control the sequential steps of the adult spinal cord neurogenesis. This review introduces the concept of adult endogenous neurogenesis, the reaction of ependymal cells after adult spinal cord injury （SCI）, the heterogeneity and markers of ependymal cells, the factors that regulate ependymal cells, and the niches that impact the activation or differentiation of ependymal ceils.
