Mammalian mitochondria have small genomes encoding very limited numbers of proteins.Over one thousand proteins and noncoding RNAs encoded by the nuclear genome must be imported from the cytosol into the mitochondria.H...Mammalian mitochondria have small genomes encoding very limited numbers of proteins.Over one thousand proteins and noncoding RNAs encoded by the nuclear genome must be imported from the cytosol into the mitochondria.Here,we report the identification of hundreds of circular RNAs(mecciRNAs)encoded by the mitochondrial genome.We provide both in vitro and in vivo evidence to show that mecciRNAs facilitate the mitochondrial entry of nuclear-encoded proteins by serving as molecular chaperones in the folding of imported proteins.Known components involved in mitochondrial protein and RNA importation,such as TOM40 and PNPASE,interact with mecciRNAs and regulate protein entry.The expression of mecciRNAs is regulated,and these transcripts are critical for the adaption of mitochondria to physiological conditions and diseases such as stresses and cancers by modulating mitochondrial protein importation.mecciRNAs and their associated physiological roles add categories and functions to the known eukaryotic circular RNAs and shed novel light on the communication between mitochondria and the nucleus.展开更多
This study investigated whether free prostate-specific antigen(fPSA)performs better than total PSA(tPSA)in predicting prostate volume(PV)in Chinese men with different PSA levels.A total of 5463 men with PSA levels of&...This study investigated whether free prostate-specific antigen(fPSA)performs better than total PSA(tPSA)in predicting prostate volume(PV)in Chinese men with different PSA levels.A total of 5463 men with PSA levels of<10 ng ml^(−1) and without prostate cancer diagnosis were included in this study.Patients were classified into four groups:PSA<2.5 ng ml^(−1),2.5–3.9 ng ml^(−1),4.0–9.9 ng ml^(−1),and 2.5–9.9 ng ml^(−1).Pearson/Spearman's correlation coefficient(r)and receiver operating characteristic(ROC)curves were used to evaluate the ability of tPSA and fPSA to predict PV.The correlation coefficient between tPSA and PV in the PSA<2.5 ng ml^(−1) cohort(r=0.422;P<0.001)was markedly higher than those of the cohorts with PSA levels of 2.5–3.9 ng ml^(−1),4.0–9.9 ng ml^(−1),and 2.5–9.9 ng ml^(−1)(r=0.114,0.167,and 0.264,respectively;all P≤0.001),while fPSA levels did not differ significantly among different PSA groups.Area under ROC curve(AUC)analyses revealed that the performance of fPSA in predicting PV≥40 ml(AUC:0.694,0.714,and 0.727)was better than that of tPSA(AUC=0.545,0.561,and 0.611)in men with PSA levels of 2.5–3.9 ng ml^(−1),4.0–9.9 ng ml^(−1),and 2.5–9.9 ng ml^(−1),respectively,but not at PSA levels of<2.5 ng ml^(−1)(AUC:0.713 vs 0.720).These findings suggest that the relationship between tPSA and PV may vary with PSA level and that fPSA is more powerful at predicting PV only in the"gray zone"(PSA levels of 2.5–9.9 ng ml^(−1)),but its performance was similar to that of tPSA at PSA levels of<2.5 ng ml^(−1).展开更多
AIM To develop a human in vitro model of non-alcoholic fatty liver disease(NAFLD), utilising primary hepatocytes cultured in a three-dimensional(3D) perfused platform. METHODS Fat and lean culture media were developed...AIM To develop a human in vitro model of non-alcoholic fatty liver disease(NAFLD), utilising primary hepatocytes cultured in a three-dimensional(3D) perfused platform. METHODS Fat and lean culture media were developed to directly investigate the effects of fat loading on primary hepatocytes cultured in a 3D perfused culture system. Oil Red O staining was used to measure fat loading in the hepatocytes and the consumption of free fatty acids(FFA) from culture medium was monitored. Hepatic functions, gene expression profiles and adipokine release were compared for cells cultured in fat and lean conditions. To determine if fat loading in the system could be modulated hepatocytes were treated with known anti-steatotic compounds. RESULTS Hepatocytes cultured in fat medium were found to accumulate three times more fat than lean cells and fat uptake was continuous over a 14-d culture. Fat loading of hepatocytes did not cause any hepatotoxicity and significantly increased albumin production. Numerous adipokines were expressed by fatty cells and genes associated with NAFLD and liver disease were upregulated including: Insulin-like growth factorbinding protein 1, fatty acid-binding protein 3 and CYP7A1. The metabolic activity of hepatocytes cultured in fatty conditions was found to be impaired and the activities of CYP3A4 and CYP2C9 were significantlyreduced, similar to observations made in NAFLD patients. The utility of the model for drug screening was demonstrated by measuring the effects of known antisteatotic compounds. Hepatocytes, cultured under fatty conditions and treated with metformin, had a reduced cellular fat content compared to untreated controls and consumed less FFA from cell culture medium.CONCLUSION The 3D in vitro NAFLD model recapitulates many features of clinical NAFLD and is an ideal tool for analysing the efficacy of anti-steatotic compounds.展开更多
RNA molecules serve a wide range of functions that are closely linked to their structures.The basic structural units of RNA consist of single-and double-stranded regions.In order to carry out advanced functions such a...RNA molecules serve a wide range of functions that are closely linked to their structures.The basic structural units of RNA consist of single-and double-stranded regions.In order to carry out advanced functions such as catalysis and ligand binding,certain types of RNAs can adopt higher-order structures.The analysis of RNA structures has progressed alongside advancements in structural biology techniques,but it comes with its own set of challenges and corresponding solutions.In this review,we will discuss recent advances in RNA structure analysis techniques,including structural probing methods,X-ray crystallography,nuclear magnetic resonance,cryo-electron microscopy,and small-angle X-ray scattering.Often,a combination of multiple techniques is employed for the integrated analysis of RNA structures.We also survey important RNA structures that have been recently determined using various techniques.展开更多
Epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs)positively affect the initial control of non-small cell lung cancer(NSCLC).Rapidly acquired resistance to EGFR-TKIs is a major hurdle in successful...Epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs)positively affect the initial control of non-small cell lung cancer(NSCLC).Rapidly acquired resistance to EGFR-TKIs is a major hurdle in successful treatment.However,the mechanisms that control the resistance of EGFR-TKIs remain largely unknown.RNA structures have widespread and crucial functions in many biological regulations;however,the functions of RNA structures in regulating cancer drug resistance remain unclear.Here,the psoralen analysis of RNA interactions and structures(PARIS)method is used to establish the higher-order RNA structure maps of EGFRTKIs-resistant and-sensitive cells of NSCLC.Our results show that RNA structural regions are enriched in untranslated regions(UTRs)and correlate with translation efficiency(TE).Moreover,yrdC N6-threonylcarbamoyltransferase domain containing(YRDC)promotes resistance to EGFR-TKIs.RNA structure formation in YRDC 30 UTR suppresses embryonic lethal abnormal vision-like 1(ELAVL1)binding,leading to EGFR-TKI sensitivity by impairing YRDC translation.A potential therapeutic strategy for cancer treatment is provided using antisense oligonucleotide(ASO)to perturb the interaction between RNA and protein.Our study reveals an unprecedented mechanism through which the RNA structure switch modulates EGFR-TKI resistance by controlling YRDC mRNA translation in an ELAVL1-dependent manner.展开更多
This study systematically evaluates the recovery of rare earth elements（REEs） from aqueous solution and industrial wastewater using magnetic nanoparticles CuFe2O4. The industrially manufactured CuFe2O4 displays a no...This study systematically evaluates the recovery of rare earth elements（REEs） from aqueous solution and industrial wastewater using magnetic nanoparticles CuFe2O4. The industrially manufactured CuFe2O4 displays a nonlinear isotherm for REEs adsorption, suggesting limiting binding sites on the CuFe2O4 surface. The recovery of REEs increases significantly from 0.1% to 99.99% with increasing pH（2.29-8.15）. At room temperature, the maxima recovery rates of Nd, La, and Ce are observed to be in a high capacity of 51.02, 42.02, and 40.16 mg/g, respectively. No significant attenuation of REE adsorption is observed with increasing NaCl concentration from 0.001 to 1.0 mol/L, showing high selectivity of REEs even in such high NaCl concentration matrix. In addition, desorption efficiency increases with the increasing concentration of HNO3 in the range of 0.005-0.05 mol/L. When HNO3 concentration is over 0.05 mol/L, the desorption efficiency can reach almost 100% in each batch experiment. Importantly, our results show that REEs can be sorbed and recycled from liquid crystal display（LCD） polishing wastewater, suggesting that CuFe2O4 may be a good candidate in the efficient and rapid recovery of REEs from industrial wastewater.展开更多
Soil organic carbon(SOC)is the largest terrestrial carbon(C)stock,and the capacity of soils to preserve organic C(OC)varies with many factors,including land use,soil type,and soil depth.We investigated the effect of l...Soil organic carbon(SOC)is the largest terrestrial carbon(C)stock,and the capacity of soils to preserve organic C(OC)varies with many factors,including land use,soil type,and soil depth.We investigated the effect of land use change on soil particulate organic matter(POM)and mineral-associated organic matter(MOM).Surface(0–10 cm)and subsurface(60–70 cm)samples were collected from paired sites(native and cropped)of four contrasting soils.Bulk soils were separated into POM and MOM fractions,which were analyzed for mineralogy,OC,nitrogen,isotopic signatures,and14C.The POM fractions of surface soils were relatively unaffected by land use change,possibly because of the continuous input of crop residues,whereas the POM fractions in corresponding subsurface soils lost more OC.In surface soils,MOM fractions dominated by the oxides of iron and aluminum(oxide-OM)lost more OC than those dominated by phyllosilicates and quartz,which was attributed to diverse organic matter(OM)input and the extent of OC saturation limit of soils.In contrast,oxide-OM fractions were less affected than the other two MOM fractions in the subsurface soils,possibly due to OC protection via organo-mineral associations.The deviations in isotopic signature(linked with vegetation)across the fractions suggested that fresh crop residues constituted the bulk of OM in surface soils(supported by greater14C).Increased isotopic signatures and lower14C in subsurface MOM fractions suggested the association of more microbially processed,aged OC with oxide-OM fractions than with the other MOM fractions.The results reveal that the quantity and quality of OC after land use change is influenced by the nature of C input in surface soils and by mineral-organic association in subsurface soils.展开更多
The influence of γ′ precipitate on the acoustic nonlinearity is investigated for a nickel-based superalloy, which is subjected to creep deformation. During creep deformation, the cuboidal γ′ precipitate is prefere...The influence of γ′ precipitate on the acoustic nonlinearity is investigated for a nickel-based superalloy, which is subjected to creep deformation. During creep deformation, the cuboidal γ′ precipitate is preferentially coarsened in a direction perpendicular to the applied stress axis. The length and shape factor of the γ′ precipitate increase with creep time. The increase of relative acoustic nonlinearity with increasing fraction of creep life is discussed in relation to the rafting of γ′ precipitate, which is closely related to the scattering and distortion of the acoustic wave展开更多
Sperm contributes essential paternal factors,including the paternal genome,centrosome,and oocyte-activation signals,to sexual reproduction.However,it remains unresolved how sperm contributes its RNA molecules to regul...Sperm contributes essential paternal factors,including the paternal genome,centrosome,and oocyte-activation signals,to sexual reproduction.However,it remains unresolved how sperm contributes its RNA molecules to regulate early embryonic development.Here,we show that the Caenorhabditis elegans paternal protein SPE-11 assembles into granules during meiotic divisions of spermatogenesis and later matures into a perinuclear structure where sperm RNAs localize.We reconstitute an SPE-11 liquid-phase scaffold in vitro and find that SPE-11 condensates incorporate the nematode RNA,which,in turn,promotes SPE-11 phase separation.Loss of SPE-11 does not affect sperm motility or fertilization but causes pleiotropic development defects in early embryos,and spe-11 mutant males reduce m RNA levels of genes crucial for an oocyte-to-embryo transition or embryonic development.These results reveal that SPE-11 undergoes phase separation and associates with sperm RNAs that are delivered to oocytes during fertilization,providing insights into how a paternal protein regulates early embryonic development.展开更多
RNA structures are essential to support RNA functions and regulation in various biological processes. Recently, a range of novel technologies have been developed to decode genome-wide RNA structures and novel modes of...RNA structures are essential to support RNA functions and regulation in various biological processes. Recently, a range of novel technologies have been developed to decode genome-wide RNA structures and novel modes of functionality across a wide range of species. In this review, we summarize key strategies for probing the RNA structurome and discuss the pros and cons of representative technologies. In particular, these new technologies have been applied to dissect the structural landscape of the SARS-CoV-2 RNA genome. We also summarize the functionalities of RNA structures discovered in different regulatory layers-including RNA processing, transport, localization, and mRNA translation-across viruses, bacteria, animals, and plants. We review many versatile RNA structural elements in the context of different physiological and pathological processes(e.g., cell differentiation, stress response, and viral replication). Finally, we discuss future prospects for RNA structural studies to map the RNA structurome at higher resolution and at the single-molecule and single-cell level, and to decipher novel modes of RNA structures and functions for innovative applications.展开更多
The aim of this study was to evaluate the biological efficacy of a unique perpendicular protrusion of type-I collagen(Col-I)from TiO2 nanotubes(NT-EPF surface).We hypothesized that the NT-EPF surface would play bifunc...The aim of this study was to evaluate the biological efficacy of a unique perpendicular protrusion of type-I collagen(Col-I)from TiO2 nanotubes(NT-EPF surface).We hypothesized that the NT-EPF surface would play bifunctional roles in stimulating plateletmediated fibroblast recruitment and anchoring fibroblast-derived Col-I to form a perpendicular collagen assembly,mimicking the connective tissue attachment around natural teeth for the long-term maintenance of dental implants.Ti surface modification was accomplished in two steps.First,TiO2 nanotubes(NT)array was fabricated via anodization.Diameters and depths of NTs were controlled by applied voltage and duration.Subsequently,an electrophoretic fusion(EPF)method was applied to fuse Col-I into nanotube arrays in a perpendicular fashion.Surface wettability was assessed by contact angle measurement.The bioactivity of modified TiO2 surfaces was evaluated in terms of NIH3T3 fibroblast attachment,platelet activation,and collagen extension.Early attachment,aggregation,and activation of platelets as well as release of platelet-related growth factors were demonstrated on NTEPF surfaces.Platelet-mediated NIH3T3 cells migration toward NT-EPF was significantly increased and the attached cells showed a typical fibrous morphology with elongated spindle shape.A direct linkage between pseudopod-like processes of fibroblasts to NTEPF surfaces was observed.Furthermore,the engineered EPF collagen protrusion linked with cell-derived collagen in a perpendicular fashion.Within the limitation of this in vitro study,the TiO2 nanotube with perpendicular Col-I surface(NT-EPF)promoted better cell attachment,induced a strong platelet activation which suggested the ability to create a more robust soft tissue seal.展开更多
Aerobic glycolysis,also known as the Warburg effect,is a hallmark of cancer and essential for metabolism in malignancies,but its regulation and modulation in cancer cells remain poorly understood.Here,using large-scal...Aerobic glycolysis,also known as the Warburg effect,is a hallmark of cancer and essential for metabolism in malignancies,but its regulation and modulation in cancer cells remain poorly understood.Here,using large-scale functional screening,we identified a tumor-associated and broadly expressed oncogenic long noncoding RNA LINC00973.Notably,knocking down LINC00973 significantly inhibits the proliferation of multiple types of cancer cells and reduces tumor growth in vivo.Mechanistically,LINC00973 directly binds to lactate dehydrogenase A(LDHA),an essential glycolytic enzyme,and enhances its enzymatic activity,thereby promoting glycolysis.Clinically,high expression of LINC00973 is significantly associated with poor prognosis in many types of human cancers.This work demonstrates that LINC00973 modulates cancer-specific regulation of the Warburg effect,and may represent a potential target for broad-acting anti-cancer therapies.展开更多
The northern US Rocky Mountains are experiencing rapid warming. Combined analysis of Ground Temperature (GT) measurements at two high-fidelity boreholes with Surface Air Temperature (SAT) measurements near Helena Mont...The northern US Rocky Mountains are experiencing rapid warming. Combined analysis of Ground Temperature (GT) measurements at two high-fidelity boreholes with Surface Air Temperature (SAT) measurements near Helena Montana spanning the past 40 years indicate the northern US Rockies have warmed on average 0.12°C - 0.32°C/decade since 1975, at least a factor of ~5 higher than the predicted 500-year-average. Warming appears to be accelerating, with warming rates since 2013 4 - 7 times higher than the 40 year average. Though uncertainty exists, the most significant GT warming appears to occur at higher elevation. Warming estimates are consistent with modelling predictions, snowpack observations, and stream temperature studies, all suggesting rapid surface temperature change in this region during the past ~40 years. The analysis indicates GT warming measured at remote borehole sites is slightly lower than regional SAT measurements collected near urban environments. We associate the discrepancy between GT/SAT measurements to both anthropogenic effects (urban development) that increase warming at the nearest SAT measurement station and a 14-year period of anomalously low snowfall that reduces surface insulation and GT warming. Using a derived average forty-year surface warming rate of 0.22°C/ decade and regional temperature-elevation trends, we calculate that the elevation of the winter freeze line during the three coldest months of the year (December, January, and February) in the northern US Rocky Mountains is retreating upward, on average, 33 m/decade. This implies a 21% reduction in freeze-line area since 1974. If this trend continues, we estimate that within the next 40 years (by 2060), the total area where ground freeze occurs during the three coldest months of the year will be ~60% of 1974 values. Since GT measurements indicate accelerated warming, this may be an underestimate. The analysis has important implications for the snowpack-water budget for Montana and the northern US Rocky Mountains.展开更多
RNA folds into intricate structures that are crucial for its functions and regulations. To date, a multitude of approaches for probing structures of the whole transcriptome, i.e., RNA struc- turomes, have been develop...RNA folds into intricate structures that are crucial for its functions and regulations. To date, a multitude of approaches for probing structures of the whole transcriptome, i.e., RNA struc- turomes, have been developed. Applications of these approaches to different cell lines and tissues have generated a rich resource for the study of RNA structure-function relationships at a systems biology level. In this review, we first introduce the designs of these methods and their applications to study different RNA structuromes. We emphasize their technological differences especially their unique advantages and caveats. We then summarize the structural insights in RNA functions and regulations obtained from the studies of RNA structuromes. And finally, we propose potential directions for future improvements and studies.展开更多
Intermetallic materials have long been considered as potential candidates for high temperature applications due to their high strength/weight ratio, oxidation resistance, and corrosion resistance. The recent alloy des...Intermetallic materials have long been considered as potential candidates for high temperature applications due to their high strength/weight ratio, oxidation resistance, and corrosion resistance. The recent alloy design approaches undertaken by many researchers around the world allowed design of intermetallics for high strength application. Environmental embrittlement, solidification porosity, and low ductility of FeAl alloys necessitated innovative ways of processing FeAl sheets based on powder metallurgical route as opposed to an ingot route. Excellent sheets of FeAl have been processed by roll compaction followed by sintering technique using water atomized FeAl powder. Gas atomized FeAl powder was used to obtain sheets of FeAl by tape casting technique. Plasma spray technique was employed to obtain coating of FeAl alloy.展开更多
RNA can interact with RNA-binding proteins(RBPs),mRNA,or other non-coding RNAs(ncRNAs)to form complex regulatory networks.High-throughput CLIP-seq,degradome-seq,and RNA-RNA interactome sequencing methods represent pow...RNA can interact with RNA-binding proteins(RBPs),mRNA,or other non-coding RNAs(ncRNAs)to form complex regulatory networks.High-throughput CLIP-seq,degradome-seq,and RNA-RNA interactome sequencing methods represent powerful approaches to identify biologically relevant ncRNA-target and protein-ncRNA interactions.However,assigning ncRNAs to their regulatory target genes or interacting RNA-binding proteins(RBPs)remains technically challenging.Chemical modifications to mRNA also play important roles in regulating gene expression.Investigation of the functional roles of these modifications relies highly on the detection methods used.RNA structure is also critical at nearly every step of the RNA life cycle.In this review,we summarize recent advances and limitations in CLIP technologies and discuss the computational challenges of and bioinformatics tools used for decoding the functions and regulatory networks of ncRNAs.We also summarize methods used to detect RNA modifications and to probe RNA structure.展开更多
Epithelial attachment via the basal lamina on the tooth surface provides an important structural defence mechanism against bacterial invasion in combating periodontal disease. However, when considering dental implants...Epithelial attachment via the basal lamina on the tooth surface provides an important structural defence mechanism against bacterial invasion in combating periodontal disease. However, when considering dental implants, strong epithelial attachment does not exist throughout the titanium-soft tissue interface, making soft tissues more susceptible to peri-implant disease. This study introduced a novel synthetic peptide(A10) to enhance epithelial attachment. A10 was identified from a bacterial peptide display library and synthesized. A10 and protease-activated receptor 4-activating peptide(PAR4-AP, positive control) were immobilized on commercially pure titanium. The peptide-treated titanium showed high epithelial cell migration ability during incubation in platelet-rich plasma. We confirmed the development of dense and expanded BL(stained by Ln5) with pericellular junctions(stained by ZO1) on the peptide-treated titanium surface. In an adhesion assay of epithelial cells on A10-treated titanium, PAR4-AP-treated titanium, bovine root and non-treated titanium, A10-treated titanium and PAR4-AP-treated titanium showed significantly stronger adhesion than non-treated titanium. PAR4-AP-treated titanium showed significantly higher inflammatory cytokine release than non-treated titanium. There was no significant difference in inflammatory cytokine release between A10-treated and non-treated titanium. These results indicated that A10 could induce the adhesion and migration of epithelial cells with low inflammatory cytokine release. This novel peptide has a potentially useful application that could improve clinical outcomes with titanium implants and abutments by reducing or preventing peri-implant disease.展开更多
基金Supported by grants to G. S.: the National Key R&D Program of China (2019YFA0802600 and 2018YFC1004500)the National Natural Science Foundation of China (31725016, 31930019, and 91940303)and the Strategic Priority Research Program (Pilot Study) “Biological basis of aging and therapeutic strategies” of the Chinese Academy of Sciences (XDPB10).
文摘Mammalian mitochondria have small genomes encoding very limited numbers of proteins.Over one thousand proteins and noncoding RNAs encoded by the nuclear genome must be imported from the cytosol into the mitochondria.Here,we report the identification of hundreds of circular RNAs(mecciRNAs)encoded by the mitochondrial genome.We provide both in vitro and in vivo evidence to show that mecciRNAs facilitate the mitochondrial entry of nuclear-encoded proteins by serving as molecular chaperones in the folding of imported proteins.Known components involved in mitochondrial protein and RNA importation,such as TOM40 and PNPASE,interact with mecciRNAs and regulate protein entry.The expression of mecciRNAs is regulated,and these transcripts are critical for the adaption of mitochondria to physiological conditions and diseases such as stresses and cancers by modulating mitochondrial protein importation.mecciRNAs and their associated physiological roles add categories and functions to the known eukaryotic circular RNAs and shed novel light on the communication between mitochondria and the nucleus.
基金supported by grants from Guangzhou Municipal Science and Technology,China (grant No.201804010453 to PT,and grant No.201904010256 to CSK)Medical Scientific Research Foundation of Guangdong Province,China (grant No.A2018503 to MPH)Scientific and Technological Projects,Guangdong Province (grant No.2015A020210005 to SLM).
文摘This study investigated whether free prostate-specific antigen(fPSA)performs better than total PSA(tPSA)in predicting prostate volume(PV)in Chinese men with different PSA levels.A total of 5463 men with PSA levels of<10 ng ml^(−1) and without prostate cancer diagnosis were included in this study.Patients were classified into four groups:PSA<2.5 ng ml^(−1),2.5–3.9 ng ml^(−1),4.0–9.9 ng ml^(−1),and 2.5–9.9 ng ml^(−1).Pearson/Spearman's correlation coefficient(r)and receiver operating characteristic(ROC)curves were used to evaluate the ability of tPSA and fPSA to predict PV.The correlation coefficient between tPSA and PV in the PSA<2.5 ng ml^(−1) cohort(r=0.422;P<0.001)was markedly higher than those of the cohorts with PSA levels of 2.5–3.9 ng ml^(−1),4.0–9.9 ng ml^(−1),and 2.5–9.9 ng ml^(−1)(r=0.114,0.167,and 0.264,respectively;all P≤0.001),while fPSA levels did not differ significantly among different PSA groups.Area under ROC curve(AUC)analyses revealed that the performance of fPSA in predicting PV≥40 ml(AUC:0.694,0.714,and 0.727)was better than that of tPSA(AUC=0.545,0.561,and 0.611)in men with PSA levels of 2.5–3.9 ng ml^(−1),4.0–9.9 ng ml^(−1),and 2.5–9.9 ng ml^(−1),respectively,but not at PSA levels of<2.5 ng ml^(−1)(AUC:0.713 vs 0.720).These findings suggest that the relationship between tPSA and PV may vary with PSA level and that fPSA is more powerful at predicting PV only in the"gray zone"(PSA levels of 2.5–9.9 ng ml^(−1)),but its performance was similar to that of tPSA at PSA levels of<2.5 ng ml^(−1).
基金Supported by Innovate UK(Technology Strategy Board)Advancing the Development and Application of Non-Animal Technologies Project:3D cell culture model for studying NonAlcoholic Fatty Liver Disease(NAFLD)-Ref:131720
文摘AIM To develop a human in vitro model of non-alcoholic fatty liver disease(NAFLD), utilising primary hepatocytes cultured in a three-dimensional(3D) perfused platform. METHODS Fat and lean culture media were developed to directly investigate the effects of fat loading on primary hepatocytes cultured in a 3D perfused culture system. Oil Red O staining was used to measure fat loading in the hepatocytes and the consumption of free fatty acids(FFA) from culture medium was monitored. Hepatic functions, gene expression profiles and adipokine release were compared for cells cultured in fat and lean conditions. To determine if fat loading in the system could be modulated hepatocytes were treated with known anti-steatotic compounds. RESULTS Hepatocytes cultured in fat medium were found to accumulate three times more fat than lean cells and fat uptake was continuous over a 14-d culture. Fat loading of hepatocytes did not cause any hepatotoxicity and significantly increased albumin production. Numerous adipokines were expressed by fatty cells and genes associated with NAFLD and liver disease were upregulated including: Insulin-like growth factorbinding protein 1, fatty acid-binding protein 3 and CYP7A1. The metabolic activity of hepatocytes cultured in fatty conditions was found to be impaired and the activities of CYP3A4 and CYP2C9 were significantlyreduced, similar to observations made in NAFLD patients. The utility of the model for drug screening was demonstrated by measuring the effects of known antisteatotic compounds. Hepatocytes, cultured under fatty conditions and treated with metformin, had a reduced cellular fat content compared to untreated controls and consumed less FFA from cell culture medium.CONCLUSION The 3D in vitro NAFLD model recapitulates many features of clinical NAFLD and is an ideal tool for analysing the efficacy of anti-steatotic compounds.
基金National Key R&D Program of China(2021YFA1301500,2017YFA0504600,2022YFC2303700,2022YFA1302700,2022YFF1203100)National Natural Science Foundation of China(U1832215,32171191,91940302,32230018 and 32125007)+6 种基金Strategic Priority Research Program of Chinese Academy of Sciences(XDB37010201,XDB0490000)Center for Advanced Interdisciplinary Science and Biomedicine of IHM(QYPY20220019)the Fundamental Research Funds for the Central Universities(WK9100000032 and WK9100000044)Guangdong Science and Technology Department(2022A1515010328,2020B1212060018 and 2020B1212030004)the Postdoctoral Foundation of Tsinghua-Peking Center for Life Sciences[to J.Z.]the Beijing Advanced Innovation Center for Structural Biology[to Q.C.Z.]the Tsinghua-Peking Joint Center for Life Sciences[to Q.C.Z.].
文摘RNA molecules serve a wide range of functions that are closely linked to their structures.The basic structural units of RNA consist of single-and double-stranded regions.In order to carry out advanced functions such as catalysis and ligand binding,certain types of RNAs can adopt higher-order structures.The analysis of RNA structures has progressed alongside advancements in structural biology techniques,but it comes with its own set of challenges and corresponding solutions.In this review,we will discuss recent advances in RNA structure analysis techniques,including structural probing methods,X-ray crystallography,nuclear magnetic resonance,cryo-electron microscopy,and small-angle X-ray scattering.Often,a combination of multiple techniques is employed for the integrated analysis of RNA structures.We also survey important RNA structures that have been recently determined using various techniques.
基金supported by grants from the Province and Ministry Coconstruction Major Program of Medical Science and Technique Foundation of Henan Province,China(Grant No.SBGJ202001007)the National Natural Science Foundation of China(Grant Nos.31870809 and 32121001)the Special Fund for Young and Middle School Leaders of Henan Health Commission,China(Grant No.HNSWJW-2020017).
文摘Epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs)positively affect the initial control of non-small cell lung cancer(NSCLC).Rapidly acquired resistance to EGFR-TKIs is a major hurdle in successful treatment.However,the mechanisms that control the resistance of EGFR-TKIs remain largely unknown.RNA structures have widespread and crucial functions in many biological regulations;however,the functions of RNA structures in regulating cancer drug resistance remain unclear.Here,the psoralen analysis of RNA interactions and structures(PARIS)method is used to establish the higher-order RNA structure maps of EGFRTKIs-resistant and-sensitive cells of NSCLC.Our results show that RNA structural regions are enriched in untranslated regions(UTRs)and correlate with translation efficiency(TE).Moreover,yrdC N6-threonylcarbamoyltransferase domain containing(YRDC)promotes resistance to EGFR-TKIs.RNA structure formation in YRDC 30 UTR suppresses embryonic lethal abnormal vision-like 1(ELAVL1)binding,leading to EGFR-TKI sensitivity by impairing YRDC translation.A potential therapeutic strategy for cancer treatment is provided using antisense oligonucleotide(ASO)to perturb the interaction between RNA and protein.Our study reveals an unprecedented mechanism through which the RNA structure switch modulates EGFR-TKI resistance by controlling YRDC mRNA translation in an ELAVL1-dependent manner.
基金Project supported by Shanghai Natural Science Foundation(17ZR1420700)State Key Laboratory of Pollution Control and Resource Reuse Foundation(PCRRF16013)Shanghai Gaofeng & Gaoyuan Project for University Academic Program Development
文摘This study systematically evaluates the recovery of rare earth elements（REEs） from aqueous solution and industrial wastewater using magnetic nanoparticles CuFe2O4. The industrially manufactured CuFe2O4 displays a nonlinear isotherm for REEs adsorption, suggesting limiting binding sites on the CuFe2O4 surface. The recovery of REEs increases significantly from 0.1% to 99.99% with increasing pH（2.29-8.15）. At room temperature, the maxima recovery rates of Nd, La, and Ce are observed to be in a high capacity of 51.02, 42.02, and 40.16 mg/g, respectively. No significant attenuation of REE adsorption is observed with increasing NaCl concentration from 0.001 to 1.0 mol/L, showing high selectivity of REEs even in such high NaCl concentration matrix. In addition, desorption efficiency increases with the increasing concentration of HNO3 in the range of 0.005-0.05 mol/L. When HNO3 concentration is over 0.05 mol/L, the desorption efficiency can reach almost 100% in each batch experiment. Importantly, our results show that REEs can be sorbed and recycled from liquid crystal display（LCD） polishing wastewater, suggesting that CuFe2O4 may be a good candidate in the efficient and rapid recovery of REEs from industrial wastewater.
基金the financial support of the International Postgraduate Research Scholarships and Postgraduate Research Support Scheme of the University of Sydneythe Australian Institute of Nuclear Science and Engineering for providing a research grant(No.ALNGRA15536)for accelerator mass spectrometry14C analysis。
文摘Soil organic carbon(SOC)is the largest terrestrial carbon(C)stock,and the capacity of soils to preserve organic C(OC)varies with many factors,including land use,soil type,and soil depth.We investigated the effect of land use change on soil particulate organic matter(POM)and mineral-associated organic matter(MOM).Surface(0–10 cm)and subsurface(60–70 cm)samples were collected from paired sites(native and cropped)of four contrasting soils.Bulk soils were separated into POM and MOM fractions,which were analyzed for mineralogy,OC,nitrogen,isotopic signatures,and14C.The POM fractions of surface soils were relatively unaffected by land use change,possibly because of the continuous input of crop residues,whereas the POM fractions in corresponding subsurface soils lost more OC.In surface soils,MOM fractions dominated by the oxides of iron and aluminum(oxide-OM)lost more OC than those dominated by phyllosilicates and quartz,which was attributed to diverse organic matter(OM)input and the extent of OC saturation limit of soils.In contrast,oxide-OM fractions were less affected than the other two MOM fractions in the subsurface soils,possibly due to OC protection via organo-mineral associations.The deviations in isotopic signature(linked with vegetation)across the fractions suggested that fresh crop residues constituted the bulk of OM in surface soils(supported by greater14C).Increased isotopic signatures and lower14C in subsurface MOM fractions suggested the association of more microbially processed,aged OC with oxide-OM fractions than with the other MOM fractions.The results reveal that the quantity and quality of OC after land use change is influenced by the nature of C input in surface soils and by mineral-organic association in subsurface soils.
文摘The influence of γ′ precipitate on the acoustic nonlinearity is investigated for a nickel-based superalloy, which is subjected to creep deformation. During creep deformation, the cuboidal γ′ precipitate is preferentially coarsened in a direction perpendicular to the applied stress axis. The length and shape factor of the γ′ precipitate increase with creep time. The increase of relative acoustic nonlinearity with increasing fraction of creep life is discussed in relation to the rafting of γ′ precipitate, which is closely related to the scattering and distortion of the acoustic wave
基金the Ministry of Science and Technology of China(2019YFA0508401)the National Natural Science Foundation of China(31871394,82121004,32100538)+3 种基金Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)the China Postdoctoral Science Foundation(2022M711844)the Young Elite Scientists Sponsorship Program by CAST(YESS20220102)ZJ Lab and Shanghai Center for Brain Science and Brain-Inspired Technology。
文摘Sperm contributes essential paternal factors,including the paternal genome,centrosome,and oocyte-activation signals,to sexual reproduction.However,it remains unresolved how sperm contributes its RNA molecules to regulate early embryonic development.Here,we show that the Caenorhabditis elegans paternal protein SPE-11 assembles into granules during meiotic divisions of spermatogenesis and later matures into a perinuclear structure where sperm RNAs localize.We reconstitute an SPE-11 liquid-phase scaffold in vitro and find that SPE-11 condensates incorporate the nematode RNA,which,in turn,promotes SPE-11 phase separation.Loss of SPE-11 does not affect sperm motility or fertilization but causes pleiotropic development defects in early embryos,and spe-11 mutant males reduce m RNA levels of genes crucial for an oocyte-to-embryo transition or embryonic development.These results reveal that SPE-11 undergoes phase separation and associates with sperm RNAs that are delivered to oocytes during fertilization,providing insights into how a paternal protein regulates early embryonic development.
基金supported by the National Key Research and Development Program of China(2021YFE0114900)the National Natural Science Foundation of China(91940303,91940306,32025008,32170262,31922039,U1832215,32170229)+6 种基金the Natural Science Foundation of Zhejiang Province(LD21C050002)the Starry Night Science Fund at Shanghai Institute for Advanced Study of Zhejiang University(SN-ZJU-SIAS-009)the Beijing Advanced Innovation Center for Structural Biology,Shenzhen Basic Research Project(JCYJ20180507181642811)Research Grants Council of the Hong Kong SAR,China Projects(City U 11100421,City U 11101519,City U 11100218,N_City U110/17)Croucher Foundation Project(9509003)State Key Laboratory of Marine Pollution Director Discretionary Fund,City University of Hong Kong Projects(7005503,9667222,9680261)the United Kingdom Biotechnology and Biological Sciences Research Council(BBSRC:BBS/E/J/000PR9788)。
文摘RNA structures are essential to support RNA functions and regulation in various biological processes. Recently, a range of novel technologies have been developed to decode genome-wide RNA structures and novel modes of functionality across a wide range of species. In this review, we summarize key strategies for probing the RNA structurome and discuss the pros and cons of representative technologies. In particular, these new technologies have been applied to dissect the structural landscape of the SARS-CoV-2 RNA genome. We also summarize the functionalities of RNA structures discovered in different regulatory layers-including RNA processing, transport, localization, and mRNA translation-across viruses, bacteria, animals, and plants. We review many versatile RNA structural elements in the context of different physiological and pathological processes(e.g., cell differentiation, stress response, and viral replication). Finally, we discuss future prospects for RNA structural studies to map the RNA structurome at higher resolution and at the single-molecule and single-cell level, and to decipher novel modes of RNA structures and functions for innovative applications.
文摘The aim of this study was to evaluate the biological efficacy of a unique perpendicular protrusion of type-I collagen(Col-I)from TiO2 nanotubes(NT-EPF surface).We hypothesized that the NT-EPF surface would play bifunctional roles in stimulating plateletmediated fibroblast recruitment and anchoring fibroblast-derived Col-I to form a perpendicular collagen assembly,mimicking the connective tissue attachment around natural teeth for the long-term maintenance of dental implants.Ti surface modification was accomplished in two steps.First,TiO2 nanotubes(NT)array was fabricated via anodization.Diameters and depths of NTs were controlled by applied voltage and duration.Subsequently,an electrophoretic fusion(EPF)method was applied to fuse Col-I into nanotube arrays in a perpendicular fashion.Surface wettability was assessed by contact angle measurement.The bioactivity of modified TiO2 surfaces was evaluated in terms of NIH3T3 fibroblast attachment,platelet activation,and collagen extension.Early attachment,aggregation,and activation of platelets as well as release of platelet-related growth factors were demonstrated on NTEPF surfaces.Platelet-mediated NIH3T3 cells migration toward NT-EPF was significantly increased and the attached cells showed a typical fibrous morphology with elongated spindle shape.A direct linkage between pseudopod-like processes of fibroblasts to NTEPF surfaces was observed.Furthermore,the engineered EPF collagen protrusion linked with cell-derived collagen in a perpendicular fashion.Within the limitation of this in vitro study,the TiO2 nanotube with perpendicular Col-I surface(NT-EPF)promoted better cell attachment,induced a strong platelet activation which suggested the ability to create a more robust soft tissue seal.
基金This work was supported by the National Natural Science Foundation of China(31371314 and 81673460)Sichuan Youth Science and Technology Innovation Research Team of Experimental Formulology(2020JDTD0022).
文摘Aerobic glycolysis,also known as the Warburg effect,is a hallmark of cancer and essential for metabolism in malignancies,but its regulation and modulation in cancer cells remain poorly understood.Here,using large-scale functional screening,we identified a tumor-associated and broadly expressed oncogenic long noncoding RNA LINC00973.Notably,knocking down LINC00973 significantly inhibits the proliferation of multiple types of cancer cells and reduces tumor growth in vivo.Mechanistically,LINC00973 directly binds to lactate dehydrogenase A(LDHA),an essential glycolytic enzyme,and enhances its enzymatic activity,thereby promoting glycolysis.Clinically,high expression of LINC00973 is significantly associated with poor prognosis in many types of human cancers.This work demonstrates that LINC00973 modulates cancer-specific regulation of the Warburg effect,and may represent a potential target for broad-acting anti-cancer therapies.
文摘The northern US Rocky Mountains are experiencing rapid warming. Combined analysis of Ground Temperature (GT) measurements at two high-fidelity boreholes with Surface Air Temperature (SAT) measurements near Helena Montana spanning the past 40 years indicate the northern US Rockies have warmed on average 0.12°C - 0.32°C/decade since 1975, at least a factor of ~5 higher than the predicted 500-year-average. Warming appears to be accelerating, with warming rates since 2013 4 - 7 times higher than the 40 year average. Though uncertainty exists, the most significant GT warming appears to occur at higher elevation. Warming estimates are consistent with modelling predictions, snowpack observations, and stream temperature studies, all suggesting rapid surface temperature change in this region during the past ~40 years. The analysis indicates GT warming measured at remote borehole sites is slightly lower than regional SAT measurements collected near urban environments. We associate the discrepancy between GT/SAT measurements to both anthropogenic effects (urban development) that increase warming at the nearest SAT measurement station and a 14-year period of anomalously low snowfall that reduces surface insulation and GT warming. Using a derived average forty-year surface warming rate of 0.22°C/ decade and regional temperature-elevation trends, we calculate that the elevation of the winter freeze line during the three coldest months of the year (December, January, and February) in the northern US Rocky Mountains is retreating upward, on average, 33 m/decade. This implies a 21% reduction in freeze-line area since 1974. If this trend continues, we estimate that within the next 40 years (by 2060), the total area where ground freeze occurs during the three coldest months of the year will be ~60% of 1974 values. Since GT measurements indicate accelerated warming, this may be an underestimate. The analysis has important implications for the snowpack-water budget for Montana and the northern US Rocky Mountains.
基金supported by the National Natural Science Foundation of China(Grant No.31671355)the National Thousand Young Talents Program of China to QCZ
文摘RNA folds into intricate structures that are crucial for its functions and regulations. To date, a multitude of approaches for probing structures of the whole transcriptome, i.e., RNA struc- turomes, have been developed. Applications of these approaches to different cell lines and tissues have generated a rich resource for the study of RNA structure-function relationships at a systems biology level. In this review, we first introduce the designs of these methods and their applications to study different RNA structuromes. We emphasize their technological differences especially their unique advantages and caveats. We then summarize the structural insights in RNA functions and regulations obtained from the studies of RNA structuromes. And finally, we propose potential directions for future improvements and studies.
文摘Intermetallic materials have long been considered as potential candidates for high temperature applications due to their high strength/weight ratio, oxidation resistance, and corrosion resistance. The recent alloy design approaches undertaken by many researchers around the world allowed design of intermetallics for high strength application. Environmental embrittlement, solidification porosity, and low ductility of FeAl alloys necessitated innovative ways of processing FeAl sheets based on powder metallurgical route as opposed to an ingot route. Excellent sheets of FeAl have been processed by roll compaction followed by sintering technique using water atomized FeAl powder. Gas atomized FeAl powder was used to obtain sheets of FeAl by tape casting technique. Plasma spray technique was employed to obtain coating of FeAl alloy.
文摘RNA can interact with RNA-binding proteins(RBPs),mRNA,or other non-coding RNAs(ncRNAs)to form complex regulatory networks.High-throughput CLIP-seq,degradome-seq,and RNA-RNA interactome sequencing methods represent powerful approaches to identify biologically relevant ncRNA-target and protein-ncRNA interactions.However,assigning ncRNAs to their regulatory target genes or interacting RNA-binding proteins(RBPs)remains technically challenging.Chemical modifications to mRNA also play important roles in regulating gene expression.Investigation of the functional roles of these modifications relies highly on the detection methods used.RNA structure is also critical at nearly every step of the RNA life cycle.In this review,we summarize recent advances and limitations in CLIP technologies and discuss the computational challenges of and bioinformatics tools used for decoding the functions and regulatory networks of ncRNAs.We also summarize methods used to detect RNA modifications and to probe RNA structure.
基金supported by an International Team for Implantology(ITI)grant(grant number:1119_2015)
文摘Epithelial attachment via the basal lamina on the tooth surface provides an important structural defence mechanism against bacterial invasion in combating periodontal disease. However, when considering dental implants, strong epithelial attachment does not exist throughout the titanium-soft tissue interface, making soft tissues more susceptible to peri-implant disease. This study introduced a novel synthetic peptide(A10) to enhance epithelial attachment. A10 was identified from a bacterial peptide display library and synthesized. A10 and protease-activated receptor 4-activating peptide(PAR4-AP, positive control) were immobilized on commercially pure titanium. The peptide-treated titanium showed high epithelial cell migration ability during incubation in platelet-rich plasma. We confirmed the development of dense and expanded BL(stained by Ln5) with pericellular junctions(stained by ZO1) on the peptide-treated titanium surface. In an adhesion assay of epithelial cells on A10-treated titanium, PAR4-AP-treated titanium, bovine root and non-treated titanium, A10-treated titanium and PAR4-AP-treated titanium showed significantly stronger adhesion than non-treated titanium. PAR4-AP-treated titanium showed significantly higher inflammatory cytokine release than non-treated titanium. There was no significant difference in inflammatory cytokine release between A10-treated and non-treated titanium. These results indicated that A10 could induce the adhesion and migration of epithelial cells with low inflammatory cytokine release. This novel peptide has a potentially useful application that could improve clinical outcomes with titanium implants and abutments by reducing or preventing peri-implant disease.
