Infectious bone defects represent a substantial challenge in clinical practice,necessitating the deployment of advanced therapeutic strategies.This study presents a treatment modality that merges a mild photothermal t...Infectious bone defects represent a substantial challenge in clinical practice,necessitating the deployment of advanced therapeutic strategies.This study presents a treatment modality that merges a mild photothermal therapy hydrogel with a pulsed drug delivery mechanism.The system is predicated on a hydrogel matrix that is thermally responsive,characteristic of bone defect sites,facilitating controlled and site-specific drug release.The cornerstone of this system is the incorporation of mild photothermal nanoparticles,which are activated within the temperature range of 40–43°C,thereby enhancing the precision and efficacy of drug delivery.Our findings demonstrate that the photothermal response significantly augments the localized delivery of therapeutic agents,mitigating systemic side effects and bolstering efficacy at the defect site.The synchronized pulsed release,cooperated with mild photothermal therapy,effectively addresses infection control,and promotes bone regeneration.This approach signifies a considerable advancement in the management of infectious bone defects,offering an effective and patient-centric alternative to traditional methods.Our research endeavors to extend its applicability to a wider spectrum of tissue regeneration scenarios,underscoring its transformative potential in the realm of regenerative medicine.展开更多
Insufficient alveolar bone thickness increases the risk of periodontal dehiscence and fenestration,especially in orthodontic tooth movement.Abaloparatide(ABL),a synthetic analog of human PTHr P(1–34)and a clinical me...Insufficient alveolar bone thickness increases the risk of periodontal dehiscence and fenestration,especially in orthodontic tooth movement.Abaloparatide(ABL),a synthetic analog of human PTHr P(1–34)and a clinical medication for treating osteoporosis,has recently demonstrated its potential in enhancing craniofacial bone formation.Herein,we show that intraoral submucosal injection of ABL,when combined with mechanical force,promotes in situ alveolar bone thickening.The newly formed bone is primarily located outside the original compact bone,implying its origin from the periosteum.RNA sequencing of the alveolar bone tissue revealed that the focal adhesion(FA)pathway potentially mediates this bioprocess.Local injection of ABL alone enhances cell proliferation,collagen synthesis,and phosphorylation of focal adhesion kinase(FAK)in the alveolar periosteum;when ABL is combined with mechanical force,the FAK expression is upregulated,in line with the accomplishment of the ossification.In vitro,ABL enhances proliferation,migration,and FAK phosphorylation in periosteal stem cells.Furthermore,the pro-osteogenic effects of ABL on alveolar bone are entirely blocked when FAK activity is inhibited by a specific inhibitor.In summary,abaloparatide combined with mechanical force promotes alveolar bone formation via FAK-mediated periosteal osteogenesis.Thus,we have introduced a promising therapeutic approach for drug-induced in situ alveolar bone augmentation,which may prevent or repair the detrimental periodontal dehiscence,holding significant potential in dentistry.展开更多
Issues caused by maxillofacial tumours involve not only dealing with tumours but also repairing jaw bone defects.In traditional tumour therapy,the systemic toxicity of chemotherapeutic drugs,invasive surgical resectio...Issues caused by maxillofacial tumours involve not only dealing with tumours but also repairing jaw bone defects.In traditional tumour therapy,the systemic toxicity of chemotherapeutic drugs,invasive surgical resection,intractable tumour recurrence,and metastasis are major threats to the patients’lives in the clinic.Fortunately,biomaterial-based intervention can improve the efficiency of tumour treatment and decrease the possibility of recurrence and metastasis,suggesting new promising antitumour therapies.In addition,maxillofacial bone tissue defects caused by tumours and their treatment can negatively affect the physiological and psychological health of patients,and investment in treatment can result in a multitude of burdens to society.Biomaterials are promising options because they have good biocompatibility and bioactive properties for stimulation of bone regeneration.More interestingly,an integrated material regimen that combines tumour therapy with bone repair is a promising treatment option.Herein,we summarized traditional and biomaterial-mediated maxillofacial tumour treatments and analysed biomaterials for bone defect repair.Furthermore,we proposed a promising and superior design of dual-functional biomaterials for simultaneous tumour therapy and bone regeneration to provide a new strategy for managing maxillofacial tumours and improve the quality of life of patients in the future.展开更多
Preeclampsia(PE)refers to a group of dysfunction syndromes associated with elevated blood pressure and proteinuria in women with previously normal blood pressure after 20 weeks of pregnancy,and it may be accompanied b...Preeclampsia(PE)refers to a group of dysfunction syndromes associated with elevated blood pressure and proteinuria in women with previously normal blood pressure after 20 weeks of pregnancy,and it may be accompanied by symptoms including headache。展开更多
Gas production from multiple coal seams has become common practice in many coal basins around the world. Although gas production rates are typically enhanced, the economic viability of such practice is not well studie...Gas production from multiple coal seams has become common practice in many coal basins around the world. Although gas production rates are typically enhanced, the economic viability of such practice is not well studied. In order to investigate the technical and economic feasibility of multiple coal seams production, reservoir simulation integrated with economics modelling was performed to study the effect of important reservoir properties of the secondary coal seam on production and economic performance using both vertical and horizontal wells. The results demonstrated that multiple seam gas production of using both vertical and horizontal wells have competitive advantage over single layer production under most scenarios. Gas content and permeability of the secondary coal seam are the most important reservoir properties that have impact on the economic feasibility of multiple seam gas production. The comparison of vertical well and horizontal well performance showed that horizontal well is more economically attractive for both single well and gas field. Moreover, wellhead price is the most sensitive to the economic performance, followed by operating costs and government subsidy. Although the results of reservoir simulation combined with economic analysis are subject to assumptions, multiple seam gas production is more likely to maintain profitability compared with single layer production.展开更多
LncRNAs and metabolism represents two factors involved in cancer initiation and progression.However,the interaction between lncRNAs and metabolism remains to be fully explored.In this study,lncRNA FEZF1-AS1(FEZF1-AS1)...LncRNAs and metabolism represents two factors involved in cancer initiation and progression.However,the interaction between lncRNAs and metabolism remains to be fully explored.In this study,lncRNA FEZF1-AS1(FEZF1-AS1)was found upregulated in colon cancer after screening all the lncRNAs of colon cancer tissues deposited in TCGA,the result of which was further confirmed by RNAscope staining on a colon tissue chip.The results obtained using FEZF1-AS1 knockout colon cancer cells(SW480 KO and HCT-116 KO)constructed using CRISPR/Cas9 system confirmed the proliferation,invasion,and migration-promoting function of FEZF1-AS1 in vitro.Mechanistically,FEZF1-AS1 associated with the mitochondrial protein phosphoenolpyruvate carboxykinase(PCK2),which plays an essential role in regulating energy metabolism in the mitochondria.Knockdown of FEZF1-AS1 greatly decreased PCK2 protein levels,broke the homeostasis of energy metabolism in the mitochondria,and inhibited proliferation,invasion,and migration of SW480 and HCT-116 cells.PCK2 overexpression in FEZF1-AS1 knockout cells partially rescued the tumor inhibitory effect on colon cancer cells both in vitro and in vivo.Moreover,PCK2 overexpression specifically rescued the abnormal accumulation of Flavin mononucleotide(FMN)and succinate,both of which play an important role in oxidative phosphorylation(OXPHOS).Overall,these results indicate that FEZF1-AS1 is an oncogene through regulating energy metabolism of the cell.This research reveals a new mechanism for lncRNAs to regulate colon cancer and provides a potential target for colon cancer diagnosis and treatment.展开更多
In order to study the modification effect of recycled sand on cement reinforced waste slurry(CWS),triaxial test,scanning electron microscope test and X-ray diffraction test were carried out.The mechanical test of recy...In order to study the modification effect of recycled sand on cement reinforced waste slurry(CWS),triaxial test,scanning electron microscope test and X-ray diffraction test were carried out.The mechanical test of recycled sand and cement reinforced waste slurry(RCWS)shows that the deviatoric stress–strain curve of RCWS samples changes from hardening type to softening type with the increase of recycled sand content;the peak stress increases with the increase of recycled sand content;recycled sand can enhance the shear strength of CWS by increasing both cohesion and internal friction angle.The microscopic test shows that recycled sand can improve the structural compactness by cementing with hydrated calcium silicate and can reduce the void ratio and orientation index of RCWS samples.Finally,the mathematical model between shear strength parameters and void ratio is established.The research shows that adding an appropriate amount of recycled sand and cement has a good modification effect on waste slurry.This is an effective method to treat two kinds of construction wastes:construction waste slurry and waste concrete.展开更多
Antenatal depression is a significant contributor to maternal morbidity in the perinatal period[1].It has also been associated with an increased risk for premature delivery,decreased rates of breastfeeding initiation,...Antenatal depression is a significant contributor to maternal morbidity in the perinatal period[1].It has also been associated with an increased risk for premature delivery,decreased rates of breastfeeding initiation,and a broad range of adverse child out-comes,including emotional problems,externalizing difficulties,attachment issues,and poorer cognitive development[2-6]Depression in the antenatal period may persist postnatally and increase in severity further exacerbating the negative conse-quences.There are considerable geographical differences in ante-natal depression prevalence rates across China,ranging from 9.8%to 35.4%,which is likely due to variations in demographic,lifestyle,social,and economic factors[7,8].Heterogeneity in study design and data source has also resulted in these wide variations.Further,previous Chinese studies examining antenatal depression have been limited due to relatively small sample sizes,short study peri-ods,and a focus on only one specific geographical district.Limited prevalence data in China suggest that a large-scale multi-center study is warranted.展开更多
Huang et al.[1]have put forward reasonable suggestions regarding certain findings of our recently published article,specifically including:(i)the cut-off values and limitations of the Edinburgh Postnatal Depression Sc...Huang et al.[1]have put forward reasonable suggestions regarding certain findings of our recently published article,specifically including:(i)the cut-off values and limitations of the Edinburgh Postnatal Depression Scale(EPDS);(ii)the restriction of data collection in our study to the third trimester;(iii)the sampling methodology employed in this study;(iv)the use of binary versus ternary classification for EPDS scores;(v)the lack of 95%confidence intervals for prevalence estimates;and(vi)the assessment of participants’prior mental health history.As described in this Reply,we interpreted the results of our article by reviewing and referring to other published articles.展开更多
As shown in our previous study, two alternatively spliced androgen receptor(AR) variants, which are exclusively expressed in the granulosa cells of patients with polycystic ovary syndrome, exhibit retarded nuclear tra...As shown in our previous study, two alternatively spliced androgen receptor(AR) variants, which are exclusively expressed in the granulosa cells of patients with polycystic ovary syndrome, exhibit retarded nuclear translocation compared with wild-type AR. However, researchers have not yet determined whether these abnormalities correlate with heat shock protein 90(HSP90)and importin α(the former is a generally accepted co-chaperone of AR, and the latter is a component of classical nuclear import complexes). Here, these two variants were mainly retained in cytoplasm with HSP90 and importin α in the presence of dihydrotestosterone(DHT), and their levels in nucleus were significantly reduced, according to the immunofluorescence staining. The binding affinity of two AR variants for importin α was consistently decreased, while it was increased in WT-AR following DHT stimulation, leading to reduced nuclear import, particularly for the insertion-AR(Ins-AR). However, the binding affinities of two AR variants for HSP90 were increased in the absence of DHT compared with WT-AR, which functioned to maintain spatial structural stability, particularly for the deletion-AR(Del-AR). Therefore, the retarded nuclear translocation of two AR variants is associated with HSP90 and importin α, and the abnormal binding affinities for them play critical roles in this process.展开更多
Osteosarcoma is a malignant bone tumor,which often occurs in adolescents.However,surgical resection usually fails to completely remove the tumor clinically,which has been the main cause of postoperative recurrence and...Osteosarcoma is a malignant bone tumor,which often occurs in adolescents.However,surgical resection usually fails to completely remove the tumor clinically,which has been the main cause of postoperative recurrence and metastasis,resulting in the high death rate of patients.At the same time,osteosarcoma invades a large area of the bone defect,which cannot be self-repaired and seriously affects the life quality of the patients.Herein,a bifunctional methacrylated gelatin/methacrylated chondroitin sulfate hydrogel hybrid gold nanorods(GNRs)and nanohydroxyapatite(nHA),which possessed excellent photothermal effect,was constructed to eradicate residual tumor after surgery and bone regeneration.In vitro,K7M2wt cells(a mouse bone tumor cell line)can be efficiently eradicated by photothermal therapy of the hybrid hydrogel.Meanwhile,the hydrogel mimics the extracellular matrix to promote proliferation and osteogenic differentiation of mesenchymal stem cells.The GNRs/nHA hybrid hydrogel was capable of photothermal treatment of postoperative tumors and bone defect repair in a mice model of tibia osteosarcoma.Therefore,the hybrid hydrogel possesses dual functions of tumor therapy and bone regeneration,which shows great potential in curing bone tumors and provides a new hope for tumor-related bone complex disease.展开更多
Preimplantation genetic testing(PGT)is a precise and effective technique for detecting inherited pathogenic mutations to prevent birth defects.However,there are few reports on PGT for pseudo-autosomal genetic diseases.
基金supported by the National Natural Science Foundation of China(32171354,82222015,82171001)The National Key Research and Development Program of China2023YFC2413600Research Funding from West China School/Hospital of Stomatology,Sichuan University(No.RCDWIS2023-1).
文摘Infectious bone defects represent a substantial challenge in clinical practice,necessitating the deployment of advanced therapeutic strategies.This study presents a treatment modality that merges a mild photothermal therapy hydrogel with a pulsed drug delivery mechanism.The system is predicated on a hydrogel matrix that is thermally responsive,characteristic of bone defect sites,facilitating controlled and site-specific drug release.The cornerstone of this system is the incorporation of mild photothermal nanoparticles,which are activated within the temperature range of 40–43°C,thereby enhancing the precision and efficacy of drug delivery.Our findings demonstrate that the photothermal response significantly augments the localized delivery of therapeutic agents,mitigating systemic side effects and bolstering efficacy at the defect site.The synchronized pulsed release,cooperated with mild photothermal therapy,effectively addresses infection control,and promotes bone regeneration.This approach signifies a considerable advancement in the management of infectious bone defects,offering an effective and patient-centric alternative to traditional methods.Our research endeavors to extend its applicability to a wider spectrum of tissue regeneration scenarios,underscoring its transformative potential in the realm of regenerative medicine.
基金supported by the National Natural Science Foundation of China(NSFC)(82371003)the Elite Research Grant of the International Orthodontics Foundation 2022。
文摘Insufficient alveolar bone thickness increases the risk of periodontal dehiscence and fenestration,especially in orthodontic tooth movement.Abaloparatide(ABL),a synthetic analog of human PTHr P(1–34)and a clinical medication for treating osteoporosis,has recently demonstrated its potential in enhancing craniofacial bone formation.Herein,we show that intraoral submucosal injection of ABL,when combined with mechanical force,promotes in situ alveolar bone thickening.The newly formed bone is primarily located outside the original compact bone,implying its origin from the periosteum.RNA sequencing of the alveolar bone tissue revealed that the focal adhesion(FA)pathway potentially mediates this bioprocess.Local injection of ABL alone enhances cell proliferation,collagen synthesis,and phosphorylation of focal adhesion kinase(FAK)in the alveolar periosteum;when ABL is combined with mechanical force,the FAK expression is upregulated,in line with the accomplishment of the ossification.In vitro,ABL enhances proliferation,migration,and FAK phosphorylation in periosteal stem cells.Furthermore,the pro-osteogenic effects of ABL on alveolar bone are entirely blocked when FAK activity is inhibited by a specific inhibitor.In summary,abaloparatide combined with mechanical force promotes alveolar bone formation via FAK-mediated periosteal osteogenesis.Thus,we have introduced a promising therapeutic approach for drug-induced in situ alveolar bone augmentation,which may prevent or repair the detrimental periodontal dehiscence,holding significant potential in dentistry.
基金supported by the National Natural Science Foundation(31972925)the Sichuan Science and Technology Program(2020YJ0065)+2 种基金the Sichuan University Spark Project(2018SCUH0029)the State Key Laboratory of Oral Diseases Foundation(SKLOD202016)the Undergraduate Innovation and Entrepreneurship Training Program of Sichuan University(C2020108331).
文摘Issues caused by maxillofacial tumours involve not only dealing with tumours but also repairing jaw bone defects.In traditional tumour therapy,the systemic toxicity of chemotherapeutic drugs,invasive surgical resection,intractable tumour recurrence,and metastasis are major threats to the patients’lives in the clinic.Fortunately,biomaterial-based intervention can improve the efficiency of tumour treatment and decrease the possibility of recurrence and metastasis,suggesting new promising antitumour therapies.In addition,maxillofacial bone tissue defects caused by tumours and their treatment can negatively affect the physiological and psychological health of patients,and investment in treatment can result in a multitude of burdens to society.Biomaterials are promising options because they have good biocompatibility and bioactive properties for stimulation of bone regeneration.More interestingly,an integrated material regimen that combines tumour therapy with bone repair is a promising treatment option.Herein,we summarized traditional and biomaterial-mediated maxillofacial tumour treatments and analysed biomaterials for bone defect repair.Furthermore,we proposed a promising and superior design of dual-functional biomaterials for simultaneous tumour therapy and bone regeneration to provide a new strategy for managing maxillofacial tumours and improve the quality of life of patients in the future.
基金supported by the Welfare TechnologyApplied Research Project of Zhejiang Province(No.LGF20H 040011),China。
文摘Preeclampsia(PE)refers to a group of dysfunction syndromes associated with elevated blood pressure and proteinuria in women with previously normal blood pressure after 20 weeks of pregnancy,and it may be accompanied by symptoms including headache。
文摘Gas production from multiple coal seams has become common practice in many coal basins around the world. Although gas production rates are typically enhanced, the economic viability of such practice is not well studied. In order to investigate the technical and economic feasibility of multiple coal seams production, reservoir simulation integrated with economics modelling was performed to study the effect of important reservoir properties of the secondary coal seam on production and economic performance using both vertical and horizontal wells. The results demonstrated that multiple seam gas production of using both vertical and horizontal wells have competitive advantage over single layer production under most scenarios. Gas content and permeability of the secondary coal seam are the most important reservoir properties that have impact on the economic feasibility of multiple seam gas production. The comparison of vertical well and horizontal well performance showed that horizontal well is more economically attractive for both single well and gas field. Moreover, wellhead price is the most sensitive to the economic performance, followed by operating costs and government subsidy. Although the results of reservoir simulation combined with economic analysis are subject to assumptions, multiple seam gas production is more likely to maintain profitability compared with single layer production.
基金supported by the GDAS Special Project of Science and Technology Development (2019GDASYL-0103058)Guangdong Basic and Applied Basic Research Foundation,Natural Science Foundation of Guangdong Province (2019A1515011456).
文摘LncRNAs and metabolism represents two factors involved in cancer initiation and progression.However,the interaction between lncRNAs and metabolism remains to be fully explored.In this study,lncRNA FEZF1-AS1(FEZF1-AS1)was found upregulated in colon cancer after screening all the lncRNAs of colon cancer tissues deposited in TCGA,the result of which was further confirmed by RNAscope staining on a colon tissue chip.The results obtained using FEZF1-AS1 knockout colon cancer cells(SW480 KO and HCT-116 KO)constructed using CRISPR/Cas9 system confirmed the proliferation,invasion,and migration-promoting function of FEZF1-AS1 in vitro.Mechanistically,FEZF1-AS1 associated with the mitochondrial protein phosphoenolpyruvate carboxykinase(PCK2),which plays an essential role in regulating energy metabolism in the mitochondria.Knockdown of FEZF1-AS1 greatly decreased PCK2 protein levels,broke the homeostasis of energy metabolism in the mitochondria,and inhibited proliferation,invasion,and migration of SW480 and HCT-116 cells.PCK2 overexpression in FEZF1-AS1 knockout cells partially rescued the tumor inhibitory effect on colon cancer cells both in vitro and in vivo.Moreover,PCK2 overexpression specifically rescued the abnormal accumulation of Flavin mononucleotide(FMN)and succinate,both of which play an important role in oxidative phosphorylation(OXPHOS).Overall,these results indicate that FEZF1-AS1 is an oncogene through regulating energy metabolism of the cell.This research reveals a new mechanism for lncRNAs to regulate colon cancer and provides a potential target for colon cancer diagnosis and treatment.
基金the National Natural Science Foundation of China(41772311,52179107)College Student Xinmiao Plan of Zhejiang Province(15002001007)Student Research Fund Funded Project of Shaoxing University.
文摘In order to study the modification effect of recycled sand on cement reinforced waste slurry(CWS),triaxial test,scanning electron microscope test and X-ray diffraction test were carried out.The mechanical test of recycled sand and cement reinforced waste slurry(RCWS)shows that the deviatoric stress–strain curve of RCWS samples changes from hardening type to softening type with the increase of recycled sand content;the peak stress increases with the increase of recycled sand content;recycled sand can enhance the shear strength of CWS by increasing both cohesion and internal friction angle.The microscopic test shows that recycled sand can improve the structural compactness by cementing with hydrated calcium silicate and can reduce the void ratio and orientation index of RCWS samples.Finally,the mathematical model between shear strength parameters and void ratio is established.The research shows that adding an appropriate amount of recycled sand and cement has a good modification effect on waste slurry.This is an effective method to treat two kinds of construction wastes:construction waste slurry and waste concrete.
基金supported by the STI2030-Major Projects(2021ZD0200700)the National Key Research and Development Program of China(2021YFC2701600 and 2022YFC2703500)+10 种基金the National Natural Science Foundation of China(82088102 and 82301719)Science and Technology Innovation Fund of Shanghai Jiao Tong University(YG2020YQ29)Collaborative Innovation Program of Shanghai Municipal Health Commission(2020CXJQ01)Shanghai Municipal Commission of Health(20224Y0085 and 202340222)Open Fund Project of Guangdong Academy of Medical Sciences(YKY-KF202202)CAMS Innovation Fund for Medical Sciences(2019-I2M-5-064)Shanghai Clinical Research Center for Gynecological Diseases(22MC1940200)Shanghai Urogenital Sys-tem Diseases Research Center(2022ZZ01012)Key Discipline Con-struction Project(2023-2025)of Three-Year Initiative Plan for Strengthening Public Health System Construction in Shanghai(GWVI-11.1-35 and GWVI-11.2-YQ29)Shanghai Sailing Program(22YF1453100)Shanghai Frontiers Science Research Base of Reproduction and Development.
文摘Antenatal depression is a significant contributor to maternal morbidity in the perinatal period[1].It has also been associated with an increased risk for premature delivery,decreased rates of breastfeeding initiation,and a broad range of adverse child out-comes,including emotional problems,externalizing difficulties,attachment issues,and poorer cognitive development[2-6]Depression in the antenatal period may persist postnatally and increase in severity further exacerbating the negative conse-quences.There are considerable geographical differences in ante-natal depression prevalence rates across China,ranging from 9.8%to 35.4%,which is likely due to variations in demographic,lifestyle,social,and economic factors[7,8].Heterogeneity in study design and data source has also resulted in these wide variations.Further,previous Chinese studies examining antenatal depression have been limited due to relatively small sample sizes,short study peri-ods,and a focus on only one specific geographical district.Limited prevalence data in China suggest that a large-scale multi-center study is warranted.
文摘Huang et al.[1]have put forward reasonable suggestions regarding certain findings of our recently published article,specifically including:(i)the cut-off values and limitations of the Edinburgh Postnatal Depression Scale(EPDS);(ii)the restriction of data collection in our study to the third trimester;(iii)the sampling methodology employed in this study;(iv)the use of binary versus ternary classification for EPDS scores;(v)the lack of 95%confidence intervals for prevalence estimates;and(vi)the assessment of participants’prior mental health history.As described in this Reply,we interpreted the results of our article by reviewing and referring to other published articles.
基金supported by the National Key Research and Development Program of China (2017YFC1001303)International Cooperation Project of China and Canada NSFC (81661128010)+2 种基金National Natural Science Foundation of China (31471405, 81671456, 81671412)the National Key Basic Research Program (2013CB967404) the Doctoral Innovation Fund of School of Medicine, Shanghai Jiao Tong University (BXJ201640)
文摘As shown in our previous study, two alternatively spliced androgen receptor(AR) variants, which are exclusively expressed in the granulosa cells of patients with polycystic ovary syndrome, exhibit retarded nuclear translocation compared with wild-type AR. However, researchers have not yet determined whether these abnormalities correlate with heat shock protein 90(HSP90)and importin α(the former is a generally accepted co-chaperone of AR, and the latter is a component of classical nuclear import complexes). Here, these two variants were mainly retained in cytoplasm with HSP90 and importin α in the presence of dihydrotestosterone(DHT), and their levels in nucleus were significantly reduced, according to the immunofluorescence staining. The binding affinity of two AR variants for importin α was consistently decreased, while it was increased in WT-AR following DHT stimulation, leading to reduced nuclear import, particularly for the insertion-AR(Ins-AR). However, the binding affinities of two AR variants for HSP90 were increased in the absence of DHT compared with WT-AR, which functioned to maintain spatial structural stability, particularly for the deletion-AR(Del-AR). Therefore, the retarded nuclear translocation of two AR variants is associated with HSP90 and importin α, and the abnormal binding affinities for them play critical roles in this process.
基金supported by the National Key Research and Development Program of China(2017YFC1103500,2017YFC1103502)the National Natural Science Foundation(31972925,31771096,31930067,31525009)+3 种基金1⋅3⋅5 project for disciplines of excellence,West China Hospital,Sichuan University(ZYGD18002)Sichuan Science and Technology Program(2020YJ0065)Sichuan University Spark Project(2018SCUH0029)State Key Laboratory of Oral Diseases Foundation(SKLOD202016).
文摘Osteosarcoma is a malignant bone tumor,which often occurs in adolescents.However,surgical resection usually fails to completely remove the tumor clinically,which has been the main cause of postoperative recurrence and metastasis,resulting in the high death rate of patients.At the same time,osteosarcoma invades a large area of the bone defect,which cannot be self-repaired and seriously affects the life quality of the patients.Herein,a bifunctional methacrylated gelatin/methacrylated chondroitin sulfate hydrogel hybrid gold nanorods(GNRs)and nanohydroxyapatite(nHA),which possessed excellent photothermal effect,was constructed to eradicate residual tumor after surgery and bone regeneration.In vitro,K7M2wt cells(a mouse bone tumor cell line)can be efficiently eradicated by photothermal therapy of the hybrid hydrogel.Meanwhile,the hydrogel mimics the extracellular matrix to promote proliferation and osteogenic differentiation of mesenchymal stem cells.The GNRs/nHA hybrid hydrogel was capable of photothermal treatment of postoperative tumors and bone defect repair in a mice model of tibia osteosarcoma.Therefore,the hybrid hydrogel possesses dual functions of tumor therapy and bone regeneration,which shows great potential in curing bone tumors and provides a new hope for tumor-related bone complex disease.
基金supported by the research grants from the subproject of the China's National Key Research and Development Program(No.2021YFC2701002,2022YFC2703700,2022YFC2703702)the National Natural Science Foundation of China(No.81971344,82171677,82192864,82088102,81901495)+8 种基金the Shanghai Municipal Commission of Science and Technology Program(China)(No.22S31901500,21Y21901002,23ZR1408000)Shanghai Municipal Health Commission(No.GW-10.1-XK07)Shanghai Municipal Commission of Health and Family Planning(China)(No.202140110)CAMS Innovation Fund for Medical Sciences(No.2019-12M-5-064)Collaborative Innovation Program of Shanghai Municipal Health Commission(China)(No.2020CXJQ01)Clinical Research Plan of SHDC(China)(No.SHDC2020CR1008A)Shanghai Clinical Research Center for Gynecological Diseases(China)(No.22MC1940200)Shanghai Urogenital System Diseases Research Center(China)(No.2022ZZ01012)Shanghai Frontiers Science Research Center of Reproduction and Development(China).
文摘Preimplantation genetic testing(PGT)is a precise and effective technique for detecting inherited pathogenic mutations to prevent birth defects.However,there are few reports on PGT for pseudo-autosomal genetic diseases.
