The ovary is indispensable for female reproduction,and its age-dependent functional decline is the primary cause of infertility.However,the molecular basis of ovarian aging in higher vertebrates remains poorly underst...The ovary is indispensable for female reproduction,and its age-dependent functional decline is the primary cause of infertility.However,the molecular basis of ovarian aging in higher vertebrates remains poorly understood.Herein,we apply spatiotemporal transcriptomics to benchmark architecture organization as well as cellular and molecular determinants in young primate ovaries and compare these to aged primate ovaries.From a global view,somatic cells within the non-follicle region undergo more pronounced transcriptional fluctuation relative to those in the follicle region,likely constituting a hostile microenvironment that facilitates ovarian aging.Further,we uncovered that inflammation,the senescent-associated secretory phenotype,senescence,and fibrosis are the likely primary contributors to ovarian aging(PCOA).Of note,we identified spatial co-localization between a PCOA-featured spot and an unappreciated MT2(Metallothionein 2)highly expressing spot(MT2^(high))characterized by high levels of inflammation,potentially serving as an aging hotspot in the primate ovary.Moreover,with advanced age,a subpopulation of MT2^(high)accumulates,likely disseminating and amplifying the senescent signal outward.Our study establishes the first primate spatiotemporal transcriptomic atlas,advancing our understanding of mechanistic determinants underpinning primate ovarian aging and unraveling potential biomarkers and therapeutic targets for aging and age-associated human ovarian disorders.展开更多
The interpretation of heterometallic bonding nature is a basic work of inorganic chemistry.By means of intermetallic substitution of germylene anions with iron halide complexes CpFe(CO)_(2)I andβ-diketiminato Fe^Ⅱch...The interpretation of heterometallic bonding nature is a basic work of inorganic chemistry.By means of intermetallic substitution of germylene anions with iron halide complexes CpFe(CO)_(2)I andβ-diketiminato Fe^Ⅱchloride,the ferrogermylene complexes 3a,3b and 4a were synthesized and structurally characterized.The structural and IR characterizations show the presence of the Ge←Feπbackbonding in molecules 3a,3b and 4a.The computational works on frontier molecular orbitals and their comparison of energy states confirmed thatσdonation andπbackbonding are both weak in these molecules,despite three complexes have longer Ge-Fe bonds,whose strength decreases slightly with the degressive electron density around Fe environment in a sequence from 3a,3b to 4a.展开更多
Premature ovarian insufficiency(POI)is a heterogeneous female disorder characterized by the loss of ovarian function before the age of 40.It represents a significant detriment to female fertility.However,the known POI...Premature ovarian insufficiency(POI)is a heterogeneous female disorder characterized by the loss of ovarian function before the age of 40.It represents a significant detriment to female fertility.However,the known POI-causative genes currently account for only a fraction of cases.To elucidate the genetic factors underlying POI,we conducted whole-exome sequencing on a family with three fertile POI patients and identified a deleterious missense variant in RNF111.In a subsequent replication study involving 1,030 POI patients,this variant was not only confirmed but also accompanied by the discovery of three additional predicted deleterious RNF111 variants.These variants collectively account for eight cases,representing 0.78%of the study cohort.A further study involving 500 patients with diminished ovarian reserve also identified two additional RNF111 variants.Notably,RNF111 encodes an E3 ubiquitin ligase with a regulatory role in the TGF-β/BMP signaling pathway.Our analysis revealed that RNF111/RNF111 is predominantly expressed in the oocytes of mice,monkeys,and humans.To further investigate the functional implications of RNF111 variants,we generated two mouse models:one with a heterozygous missense mutation(Rnf111+/M)and another with a heterozygous null mutation(Rnf111^(+/-)).Both mouse models exhibited impaired female fertility,characterized by reduced litter sizes and small ovarian reserve.Additionally,RNA-seq and quantitative proteomics analysis unveiled that Rnf111 haploinsufficiency led to dysregulation in female gonad development and negative regulation of the BMP signaling pathway within mouse ovaries.In conclusion,our findings strongly suggest that monoallelic deleterious variants in RNF111 can impair female fertility and induce POI in both humans and mice.展开更多
TiO_(2)photocatalysts have been widely studied and applied for removing bacteria,but its antibacterial efficiency is limited to the ultraviolet(UV)range of the solar spectrum.In this work,we use the gold(Au)nanorods t...TiO_(2)photocatalysts have been widely studied and applied for removing bacteria,but its antibacterial efficiency is limited to the ultraviolet(UV)range of the solar spectrum.In this work,we use the gold(Au)nanorods to enhance the visible and near-infrared(NIR)light absorption of TiO_(2)NBs,a typical UV light photocatalyst,thus the enhancement of its full solar spectrum(UV,visible and NIR)photocatalytic antibacterial properties is achieved.Preliminary surface plasmon resonance(SPR)enhancement photocatalytic antibacterial mechanism is suggested.On one hand,transverse and longitudinal SPR of Au NRs is beneficial for visible and NIR light utilization.On the other hand,Au NRs combined with TiO_(2)NBs to form the heterostructure,which can improve the photogenerated carrier separation and direct electron transfer increases the hot electron concentration while Au NRs as the electron channel can well restrain charge recombination.finally produces the high yield of radical oxygen species and exhibits a superior antibacterial efficiency.Furthermore,we design a sterilization file cabinet with Au NR/TiO_(2)NB heterostructures as the photocatalytic coating plates.Our study reveals that Au NR/TiO_(2)NB heterostructure is a potential candidate for sterilization of bacteria and archives protection.展开更多
Dear Editor,Male infertility is a multifactorial heterogeneous pathological condition affecting∼7%of men.Nonobstructive azoospermia(NOA)is one of the most severe male reproductive diseases and occurs in∼1%of men of ...Dear Editor,Male infertility is a multifactorial heterogeneous pathological condition affecting∼7%of men.Nonobstructive azoospermia(NOA)is one of the most severe male reproductive diseases and occurs in∼1%of men of reproductive age.1 However,its etiology remains elusive.展开更多
基金This work was supported by the National Natural Science Foundation of China(Grant Nos.82122024,92149301,82125011,81921006)the National Key Research and Development Program of China(2022YFA1103700,2020YFA0804000,2020YFA0112200,2021YFF1201000,the STI2030-Major Projects-2021ZD0202400)+11 种基金the National Natural Science Foundation of China(Grant Nos.92168201,82225019,91949209,92049304,82071588,82322025,32000500,82271600,92049116,32121001,82192863,82201714)CAS Project for Young Scientists in Basic Research(YSBR-076,YSBR-012)the Strategic Collaborative Research Program of the Ferring Institute of Reproductive Medicine,Ferring Pharmaceuticals and the Chinese Academy of Sciences(FIRMC180305)the Program of the Beijing Natural Science Foundation(Z230011)the Informatization Plan of Chinese Academy of Sciences(CAS-WX2021SF-0301,CAS-WX2022SDC-XK14,CAS-WX2021SF-0101)New Cornerstone Science Foundation through the XPLORER PRIZE(2021-1045)Youth Innovation Promotion Association of CAS(2022083,E1CAZW0401)Excellent Young Talents Program of Capital Medical University(12300927)the Project for Technology Development of Beijing-affiliated Medical Research Institutes(11000023T000002036310)Excellent Young Talents Training Program for the Construction of Beijing Municipal University Teacher Team(BPHR202203105)Young Elite Scientists Sponsorship Program by CAST(2021QNRC001)The Fellowship of China Postdoctoral Science Foundation(2022M712216).
文摘The ovary is indispensable for female reproduction,and its age-dependent functional decline is the primary cause of infertility.However,the molecular basis of ovarian aging in higher vertebrates remains poorly understood.Herein,we apply spatiotemporal transcriptomics to benchmark architecture organization as well as cellular and molecular determinants in young primate ovaries and compare these to aged primate ovaries.From a global view,somatic cells within the non-follicle region undergo more pronounced transcriptional fluctuation relative to those in the follicle region,likely constituting a hostile microenvironment that facilitates ovarian aging.Further,we uncovered that inflammation,the senescent-associated secretory phenotype,senescence,and fibrosis are the likely primary contributors to ovarian aging(PCOA).Of note,we identified spatial co-localization between a PCOA-featured spot and an unappreciated MT2(Metallothionein 2)highly expressing spot(MT2^(high))characterized by high levels of inflammation,potentially serving as an aging hotspot in the primate ovary.Moreover,with advanced age,a subpopulation of MT2^(high)accumulates,likely disseminating and amplifying the senescent signal outward.Our study establishes the first primate spatiotemporal transcriptomic atlas,advancing our understanding of mechanistic determinants underpinning primate ovarian aging and unraveling potential biomarkers and therapeutic targets for aging and age-associated human ovarian disorders.
基金supported by National Science Foundation of China(No.22273072)the Shaanxi Provincial Enterprise Joint Fund(No.2021JLM-31)the Natural Science Basic Research Plan in Shaanxi Province of China(No.2021JM-311)。
文摘The interpretation of heterometallic bonding nature is a basic work of inorganic chemistry.By means of intermetallic substitution of germylene anions with iron halide complexes CpFe(CO)_(2)I andβ-diketiminato Fe^Ⅱchloride,the ferrogermylene complexes 3a,3b and 4a were synthesized and structurally characterized.The structural and IR characterizations show the presence of the Ge←Feπbackbonding in molecules 3a,3b and 4a.The computational works on frontier molecular orbitals and their comparison of energy states confirmed thatσdonation andπbackbonding are both weak in these molecules,despite three complexes have longer Ge-Fe bonds,whose strength decreases slightly with the degressive electron density around Fe environment in a sequence from 3a,3b to 4a.
基金supported by the National Natural Science Foundation of China(32288101)the National Key Research and Development Program of China(2021YFC2701400)Shenkang Clinical Technology Innovation Project(SHDC22021219)。
文摘Premature ovarian insufficiency(POI)is a heterogeneous female disorder characterized by the loss of ovarian function before the age of 40.It represents a significant detriment to female fertility.However,the known POI-causative genes currently account for only a fraction of cases.To elucidate the genetic factors underlying POI,we conducted whole-exome sequencing on a family with three fertile POI patients and identified a deleterious missense variant in RNF111.In a subsequent replication study involving 1,030 POI patients,this variant was not only confirmed but also accompanied by the discovery of three additional predicted deleterious RNF111 variants.These variants collectively account for eight cases,representing 0.78%of the study cohort.A further study involving 500 patients with diminished ovarian reserve also identified two additional RNF111 variants.Notably,RNF111 encodes an E3 ubiquitin ligase with a regulatory role in the TGF-β/BMP signaling pathway.Our analysis revealed that RNF111/RNF111 is predominantly expressed in the oocytes of mice,monkeys,and humans.To further investigate the functional implications of RNF111 variants,we generated two mouse models:one with a heterozygous missense mutation(Rnf111+/M)and another with a heterozygous null mutation(Rnf111^(+/-)).Both mouse models exhibited impaired female fertility,characterized by reduced litter sizes and small ovarian reserve.Additionally,RNA-seq and quantitative proteomics analysis unveiled that Rnf111 haploinsufficiency led to dysregulation in female gonad development and negative regulation of the BMP signaling pathway within mouse ovaries.In conclusion,our findings strongly suggest that monoallelic deleterious variants in RNF111 can impair female fertility and induce POI in both humans and mice.
基金fundings from the National Natural Science Foundation of China(Nos.51872173,51772176)TaishanScholars Program of Shandong Province(Nos.tsqn201812068,tspd20161006)+6 种基金Higher School Youth Innovation Team of Shandong Province(No.2019KJA013)Key Research and Development Program of Shandong Province(No.2018GGX102028)Science and Technology Special Project of Qingdao City(No.20-3-4-3-nsh)the Opening Fund of State Key Laboratory of Heavy Oil Processing(No.SKLOP202002006)Cooperative Education Project of the Ministry of Education(No.201902195026)Humanities and Social Sciences Program(GoMoruo Studies)of the Education Department of Sichuan Province(No.GY2020C01)Shandong Archives Science and Technology Project(No.2020-33)。
文摘TiO_(2)photocatalysts have been widely studied and applied for removing bacteria,but its antibacterial efficiency is limited to the ultraviolet(UV)range of the solar spectrum.In this work,we use the gold(Au)nanorods to enhance the visible and near-infrared(NIR)light absorption of TiO_(2)NBs,a typical UV light photocatalyst,thus the enhancement of its full solar spectrum(UV,visible and NIR)photocatalytic antibacterial properties is achieved.Preliminary surface plasmon resonance(SPR)enhancement photocatalytic antibacterial mechanism is suggested.On one hand,transverse and longitudinal SPR of Au NRs is beneficial for visible and NIR light utilization.On the other hand,Au NRs combined with TiO_(2)NBs to form the heterostructure,which can improve the photogenerated carrier separation and direct electron transfer increases the hot electron concentration while Au NRs as the electron channel can well restrain charge recombination.finally produces the high yield of radical oxygen species and exhibits a superior antibacterial efficiency.Furthermore,we design a sterilization file cabinet with Au NR/TiO_(2)NB heterostructures as the photocatalytic coating plates.Our study reveals that Au NR/TiO_(2)NB heterostructure is a potential candidate for sterilization of bacteria and archives protection.
基金This work was supported by the National Key R&D Program of China(2018YFA0107702,2018YFC1004200)Strategic Priority Research Program of the Chinese Academy of Sciences(XDB19000000)+2 种基金The National Science Fund for Distinguished Young Scholars(81525011)Strategic Collaborative Research Program of the Ferring Institute of Reproductive Medicine,Ferring Pharmaceuticals and Chinese Academy of Sciences(FIRMC180307)The National Natural Science Foundation of China(31970785 and 31671496).
文摘Dear Editor,Male infertility is a multifactorial heterogeneous pathological condition affecting∼7%of men.Nonobstructive azoospermia(NOA)is one of the most severe male reproductive diseases and occurs in∼1%of men of reproductive age.1 However,its etiology remains elusive.