Birds exhibit extraordinary mobility and remarkable navigational skills,obtaining guidance cues from the Earth’s magnetic field for orientation and long-distance movement.Bird species also show tremendous diversity i...Birds exhibit extraordinary mobility and remarkable navigational skills,obtaining guidance cues from the Earth’s magnetic field for orientation and long-distance movement.Bird species also show tremendous diversity in navigation strategies,with considerable differences even within the same taxa and among individuals from the same population.The highly conserved iron and iron-sulfur cluster binding magnetoreceptor(MagR)protein is suggested to enable animals,including birds,to detect the geomagnetic field and navigate accordingly.Notably,MagR is also implicated in other functions,such as electron transfer and biogenesis of iron-sulfur clusters,raising the question of whether variability exists in its biochemical and biophysical features among species,particularly birds.In the current study,we conducted a comparative analysis of MagR from two different bird species,including the migratory European robin(Erithacus rubecula)and the homing pigeon(Columba livia).Sequence alignment revealed an extremely high degree of similarity between the MagRs of these species,with only three sequence variations.Nevertheless,two of these variations underpinned significant differences in metal binding capacity,oligomeric state,and magnetic properties.These findings offer compelling evidence for the marked differences in MagR between the two avian species,potentially explaining how a highly conserved protein can mediate such diverse functions.展开更多
Iron-sulfur clusters(ISC)are essential cofactors for proteins involved in various biological processes,such as electron transport,biosynthetic reactions,DNA repair,and gene expression regulation.ISC assembly protein I...Iron-sulfur clusters(ISC)are essential cofactors for proteins involved in various biological processes,such as electron transport,biosynthetic reactions,DNA repair,and gene expression regulation.ISC assembly protein IscA1(or MagR)is found within the mitochondria of most eukaryotes.Magnetoreceptor(MagR)is a highly conserved A-type iron and iron-sulfur cluster-binding protein,characterized by two distinct types of iron-sulfur clusters,[2Fe-2S]and[3Fe-4S],each conferring unique magnetic properties.MagR forms a rod-like polymer structure in complex with photoreceptive cryptochrome(Cry)and serves as a putative magnetoreceptor for retrieving geomagnetic information in animal navigation.Although the N-terminal sequences of MagR vary among species,their specific function remains unknown.In the present study,we found that the N-terminal sequences of pigeon MagR,previously thought to serve as a mitochondrial targeting signal(MTS),were not cleaved following mitochondrial entry but instead modulated the efficiency with which iron-sulfur clusters and irons are bound.Moreover,the N-terminal region of MagR was required for the formation of a stable MagR/Cry complex.Thus,the N-terminal sequences in pigeon MagR fulfil more important functional roles than just mitochondrial targeting.These results further extend our understanding of the function of MagR and provide new insights into the origin of magnetoreception from an evolutionary perspective.展开更多
Magnetic sense,or termed magnetoreception,has evolved in a broad range of taxa within the animal kingdom to facilitate orientation and navigation.MagRs,highly conserved A-type iron-sulfur proteins,are widely distribut...Magnetic sense,or termed magnetoreception,has evolved in a broad range of taxa within the animal kingdom to facilitate orientation and navigation.MagRs,highly conserved A-type iron-sulfur proteins,are widely distributed across all phyla and play essential roles in both magnetoreception and iron-sulfur cluster biogenesis.However,the evolutionary origins and functional diversification of MagRs from their prokaryotic ancestor remain unclear.In this study,MagR sequences from 131 species,ranging from bacteria to humans,were selected for analysis,with 23 representative sequences covering species from prokaryotes to Mollusca,Arthropoda,Osteichthyes,Reptilia,Aves,and mammals chosen for protein expression and purification.Biochemical studies revealed a gradual increase in total iron content in MagRs during evolution.Three types of MagRs were identified,each with distinct iron and/or iron-sulfur cluster binding capacity and protein stability,indicating continuous expansion of the functional roles of MagRs during speciation and evolution.This evolutionary biochemical study provides valuable insights into how evolution shapes the physical and chemical properties of biological molecules such as MagRs and how these properties influence the evolutionary trajectories of MagRs.展开更多
BACKGROUND Diffusion-weighted imaging(DWI)has been developed to stage liver fibrosis.However,its diagnostic performance is inconsistent among studies.Therefore,it is worth studying the diagnostic value of various diff...BACKGROUND Diffusion-weighted imaging(DWI)has been developed to stage liver fibrosis.However,its diagnostic performance is inconsistent among studies.Therefore,it is worth studying the diagnostic value of various diffusion models for liver fibrosis in one cohort.AIM To evaluate the clinical potential of six diffusion-weighted models in liver fibrosis staging and compare their diagnostic performances.METHODS This prospective study enrolled 59 patients suspected of liver disease and scheduled for liver biopsy and 17 healthy participants.All participants underwent multi-b value DWI.The main DWI-derived parameters included Mono-apparent diffusion coefficient(ADC)from mono-exponential DWI,intravoxel incoherent motion model-derived true diffusion coefficient(IVIM-D),diffusion kurtosis imaging-derived apparent diffusivity(DKI-MD),stretched exponential model-derived distributed diffusion coefficient(SEM-DDC),fractional order calculus(FROC)model-derived diffusion coefficient(FROC-D)and FROC model-derived microstructural quantity(FROC-μ),and continuous-time random-walk(CTRW)model-derived anomalous diffusion coefficient(CTRW-D)and CTRW model-derived temporal diffusion heterogeneity index(CTRW-α).The correlations between DWI-derived parameters and fibrosis stages and the parameters’diagnostic efficacy in detecting significant fibrosis(SF)were assessed and compared.RESULTS CTRW-D(r=-0.356),CTRW-α(r=-0.297),DKI-MD(r=-0.297),FROC-D(r=-0.350),FROC-μ(r=-0.321),IVIM-D(r=-0.251),Mono-ADC(r=-0.362),and SEM-DDC(r=-0.263)were significantly correlated with fibrosis stages.The areas under the ROC curves(AUCs)of the combined index of the six models for distinguishing SF(0.697-0.747)were higher than each of the parameters alone(0.524-0.719).The DWI models’ability to detect SF was similar.The combined index of CTRW model parameters had the highest AUC(0.747).CONCLUSION The DWI models were similarly valuable in distinguishing SF in patients with liver disease.The combined index of CTRW parameters had the highest AUC.展开更多
BACKGROUND Dilaceration is a rare dental developmental anomaly characterized by an abrupt deviation along the longitudinal axis of the root in which an angulation forms between the root and the crown.Here,we report on...BACKGROUND Dilaceration is a rare dental developmental anomaly characterized by an abrupt deviation along the longitudinal axis of the root in which an angulation forms between the root and the crown.Here,we report on dilacerated bilateral maxi-llary central incisors in mixed dentition.CASE SUMMARY A 10-year-old girl presented with a chief complaint of unerupted central incisors.An oral examination and radiography provided the basis for a diagnosis of dilaceration of the maxillary central incisors.After surgical exposure of the impacted teeth,a button with an attached chain was applied to the palatal surface of teeth 11 and 21.After 8 mo,a button was bonded to the labial surface of the crown to fix an elastic chain and move the teeth toward the maxillary arch.Finally,a fixed appliance was applied to tooth alignment to Class 1 malocclusion using a 0.019×0.025-inch nickel-titanium wire.After 3 years of follow-up,the clinical findings and radiographic assessment showed that the roots had developed with vital dental pulp and healthy periodontium,were acceptable aesthetically,and showed no resorption.CONCLUSION The rare occurrences of dilacerated bilateral maxillary central incisors can be successfully treated through surgical exposure and orthodontics.展开更多
Five stems of rapeseed with abundant black microsclerotia were collected from Huangyuan County of Qinghai Province,China,and fungal isolates were obtained from the stems.They were identified based on morphology,molecu...Five stems of rapeseed with abundant black microsclerotia were collected from Huangyuan County of Qinghai Province,China,and fungal isolates were obtained from the stems.They were identified based on morphology,molecular features and specific PCR detection.The results showed that the 10 fungal isolates belonged to Verticillium longisporum lineage A1/D3.One of the 10 isolates(HW7-1)was tested for virulence on three species of rapeseed,including B.napus Zhongshuang 9,B.rapa Qingyou 9 and B.juncea Tayou 2 by conidia inoculation of HW7-1 on roots of young seedlings.Control seedlings were inoculated with V.dahliae conidia or water alone.The seedlings of these treatments were transplanted in culture mix and incubated in a growth chamber(20℃).Results suggested that the control seedlings of three cultivars appeared quite healthy,while the seedlings inoculated with HW7-1 turned yellowing leaves,seedling stunting or even death after 22 days post-inoculation.V.longisporum was re-isolated from he yellow leaves,thus fulfilling Koch's postulates.Moreover,compared to the control treatments,inoculation with HW7-1 caused flowering delay and seed yield reduction on Tayou 2 with production of microsclerotia on the stems.To our knowledge,this is the first report of V.longisporum lineage A1/D3 on rapeseed in northwestern China.展开更多
Morphological alterations in dendritic spines have been linked to changes in functional communication between neurons that affect learning and memory.Kinesin-4 KIF21A helps organize the microtubule-actin network at th...Morphological alterations in dendritic spines have been linked to changes in functional communication between neurons that affect learning and memory.Kinesin-4 KIF21A helps organize the microtubule-actin network at the cell cortex by interacting with KANK1;however,whether KIF21A modulates dendritic structure and function in neurons remains unknown.In this study,we found that KIF21A was distributed in a subset of dendritic spines,and that these KIF21A-positive spines were larger and more structurally plastic than KIF21A-negative spines.Furthermore,the interaction between KIF21A and KANK1 was found to be critical for dendritic spine morphogenesis and synaptic plasticity.Knockdown of either KIF21A or KANK1 inhibited dendritic spine morphogenesis and dendritic branching,and these deficits were fully rescued by coexpressing full-length KIF21A or KANK1,but not by proteins with mutations disrupting direct binding between KIF21A and KANK1 or binding between KANK1 and talin1.Knocking down KIF21A in the hippocampus of rats inhibited the amplitudes of long-term potentiation induced by high-frequency stimulation and negatively impacted the animals’cognitive abilities.Taken together,our findings demonstrate the function of KIF21A in modulating spine morphology and provide insight into its role in synaptic function.展开更多
The rotator cuff tear has emerged as a significant global health concern.However,existing therapies fail to fully restore the intricate bone-to-tendon gradients,resulting in compromised biomechanical functionalities o...The rotator cuff tear has emerged as a significant global health concern.However,existing therapies fail to fully restore the intricate bone-to-tendon gradients,resulting in compromised biomechanical functionalities of the reconstructed enthesis tissues.Herein,a tri-layered core–shell microfibrous scaffold with layer-specific growth factors(GFs)release is developed using coaxial electrohydrodynamic(EHD)printing for in situ cell recruitment and differentiation to facilitate gradient enthesis tissue repair.Stromal cell-derived factor-1(SDF-1)is loaded in the shell,while basic fibroblast GF,transforming GF-beta,and bone morphogenetic protein-2 are loaded in the core of the EHD-printed microfibrous scaffolds in a layer-specific manner.Correspondingly,the tri-layered microfibrous scaffolds have a core–shell fiber size of(25.7±5.1)μm,with a pore size sequentially increasing from(81.5±4.6)μm to(173.3±6.9)μm,and to(388.9±6.9μm)for the tenogenic,chondrogenic,and osteogenic instructive layers.A rapid release of embedded GFs is observed within the first 2 d,followed by a faster release of SDF-1 and a slightly slower release of differentiation GFs for approximately four weeks.The coaxial EHD-printed microfibrous scaffolds significantly promote stem cell recruitment and direct their differentiation toward tenocyte,chondrocyte,and osteocyte phenotypes in vitro.When implanted in vivo,the tri-layered core–shell microfibrous scaffolds rapidly restored the biomechanical functions and promoted enthesis tissue regeneration with native-like bone-to-tendon gradients.Our findings suggest that the microfibrous scaffolds with layer-specific GFs release may offer a promising clinical solution for enthesis regeneration.展开更多
Meiosis is a highly complex process significantly influenced by transcriptional regulation.However,studies on the mechanisms that govern transcriptomic changes during meiosis,especially in prophase I,are limited.Here,...Meiosis is a highly complex process significantly influenced by transcriptional regulation.However,studies on the mechanisms that govern transcriptomic changes during meiosis,especially in prophase I,are limited.Here,we performed single-cell ATAC-seq of human testis tissues and observed reprogramming during the transition from zygotene to pachytene spermatocytes.This event,conserved in mice,involved the deactivation of genes associated with meiosis after reprogramming and the activation of those related to spermatogenesis before their functional onset.Furthermore,we identified 282 transcriptional regulators(TRs)that underwent activation or deactivation subsequent to this process.Evidence suggested that physical contact signals from Sertoli cells may regulate these TRs in spermatocytes,while secreted ENHO signals may alter metabolic patterns in these cells.Our results further indicated that defective transcriptional reprogramming may be associated with non-obstructive azoospermia(NOA).This study revealed the importance of both physical contact and secreted signals between Sertoli cells and germ cells in meiotic progression.展开更多
Perovskite solar cells(PsCs)have developed tremendously over the past decade.However,the key factors influencing the power conversion efficiency(PCE)of PSCs remain incompletely understood,due to the complexity and cou...Perovskite solar cells(PsCs)have developed tremendously over the past decade.However,the key factors influencing the power conversion efficiency(PCE)of PSCs remain incompletely understood,due to the complexity and coupling of these structural and compositional parameters.In this research,we demon-strate an effective approach to optimize PSCs performance via machine learning(ML).To address chal-lenges posed by limited samples,we propose a feature mask(FM)method,which augments training samples through feature transformation rather than synthetic data.Using this approach,squeeze-and-excitation residual network(SEResNet)model achieves an accuracy with a root-mean-square-error(RMSE)of 0.833%and a Pearson's correlation coefficient(r)of 0.980.Furthermore,we employ the permu-tation importance(PI)algorithm to investigate key features for PCE.Subsequently,we predict PCE through high-throughput screenings,in which we study the relationship between PCE and chemical com-positions.After that,we conduct experiments to validate the consistency between predicted results by ML and experimental results.In this work,ML demonstrates the capability to predict device performance,extract key parameters from complex systems,and accelerate the transition from laboratory findings to commercialapplications.展开更多
Ammonia(NH_(3))is an important raw material for modern agriculture and industry,being widely demanded to sustain the sustainable development of modern society.Currently,the industrial production methods of NH_(3),such...Ammonia(NH_(3))is an important raw material for modern agriculture and industry,being widely demanded to sustain the sustainable development of modern society.Currently,the industrial production methods of NH_(3),such as the traditional Haber-Bosch process,have drawbacks including high energy consumption and significant carbon dioxide emissions.In recent years,the electrocatalytic nitrate reduction reaction(NO_(3)RR)powered by intermittent renewable energy sources has gradually become a multidisciplinary research hotspot,as it allows for the efficient synthesis of NH_(3)under mild conditions.In this review,we focus on the research of electrocatalysts with atomic-level site,which have attracted attention due to their extremely high atomic utilization efficiency and unique structural characteristics in the field of NO_(3)RR.Firstly,we introduce the mechanism of nitrate reduction for ammonia synthesis and discuss the in-situ characterization techniques related to the mechanism study.Secondly,we review the progress of the electrocatalysts with atomic-level site for nitrate reduction and explore the structure-activity relationship to guide the rational design of efficient catalysts.Lastly,the conclusions of this review and the challenges and prospective of this promising field are presented.展开更多
Pyraclostrobin(PYR),a widely used fungicide,has negative effects on fish and algae,but its toxicity in protozoa remains unclear.In this study,the effects of PYR on the growth,oxidative stress,and gene expression relat...Pyraclostrobin(PYR),a widely used fungicide,has negative effects on fish and algae,but its toxicity in protozoa remains unclear.In this study,the effects of PYR on the growth,oxidative stress,and gene expression related to stress and ATP-binding cassette(ABC)transporters in Tetrahymena thermophila were investigated.The result showed that the 96-h IC_(50)of PYR against T.thermophila was 17.2 mg/L.Moreover,PYR inhibited the growth of T.thermophila in concentration-or time-dependent manner.A morphological study revealed that the shape and size of T.thermophila changed,and damage of cell membrane surface was observed by scanning electron microscopy after 96 h of PYR exposure.The activities of superoxide dismutase(SOD)and catalase(CAT)increased throughout the experiment.In contrast,the glutathione(GSH)content was increased at 24 h and 48 h of exposure and decreased at 96 h.Moreover,a significant increase in malondialdehyde(MDA)level was observed in T.thermophila after96 h of exposure.Furthermore,PYR upregulated the HSP703,HSP705,GPx2,and ABAC15 gene expression in the 0.1–5-mg/L groups and downregulated the HSP704,HSP90,TGR,and ABCC52 mRNA levels at 96 h of exposure.These results suggest that PYR may exert adverse effects on T.thermophila by inducing oxidative stress and changing the gene expression related to ABC transporters and stress,which may enrich the understanding of the toxicity mechanism of PYR in aquatic organisms and provide reference data for aquatic ecological risk assessments.展开更多
Zearalenone(ZEN)is a mycotoxin that extensively contaminates food and feed,posing a significant threat to public health.However,the mechanisms behind ZEN-induced intestinal immunotoxicity remain unclear.In this study,...Zearalenone(ZEN)is a mycotoxin that extensively contaminates food and feed,posing a significant threat to public health.However,the mechanisms behind ZEN-induced intestinal immunotoxicity remain unclear.In this study,Sprague-Dawley(SD)rats were exposed to ZEN at a dosage of 5 mg/kg/day b.w.for a duration of 14 days.The results demonstrated that ZEN exposure led to notable pathological alterations and immunosuppression within the intestine.Furthermore,ZEN exposure caused a significant reduction in the levels of apolipoprotein E(ApoE)and liver X receptor(LXR)(P<0.05).Conversely,it upregulated the levels of myeloid-derived suppressor cells(MDSCs)markers(P<0.05)and decreased the presence of 27-hydroxycholesterol(27-HC)in the intestine(P<0.05).It was observed that ApoE or LXR agonists were able to mitigate the immunosuppressive effects induced by ZEN.Additionally,a bioinformatics analysis highlighted that the downregulation of ApoE might elevate the susceptibility to colorectal,breast,and lung cancers.These findings underscore the crucial role of the 27-HC/LXR/ApoE axis disruption in ZEN-induced MDSCs proliferation and subsequent inhibition of T lymphocyte activation within the rat intestine.Notably,ApoE may emerge as a pivotal target linking ZEN exposure to cancer development.展开更多
Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive ...Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive accuracy of the DRIA signature for response to immune checkpoint inhibitor(ICI) therapy in gastrointestinal(GI) cancer.Methods: A DRIA signature was established based on two previously reported DNA damage immune response assays. Clinical and gene expression data from two published GI cancer cohorts were used to assess and validate the association between the DRIA score and response to ICI therapy. The predictive accuracy of the DRIA score was validated based on one ICI-treated melanoma and three pan-cancer published cohorts.Results: The DRIA signature includes three genes(CXCL10, IDO1, and IFI44L). In the discovery cancer cohort, DRIA-high patients with gastric cancer achieved a higher response rate to ICI therapy than DRIA-low patients(81.8% vs. 8.8%;P < 0.001), and the predictive accuracy of the DRIA score [area under the receiver operating characteristic curve(AUC) = 0.845] was superior to the predictive accuracy of PD-L1 expression, tumor mutational burden, microsatellite instability, and Epstein–Barr virus status. The validation cohort demonstrated that the DRIA score identified responders with microsatellite-stable colorectal and pancreatic adenocarcinoma who received dual PD-1 and CTLA-4 blockade with radiation therapy. Furthermore, the predictive performance of the DRIA score was shown to be robust through an extended validation in melanoma, urothelial cancer, and pan-cancer.Conclusions: The DRIA signature has superior and robust predictive accuracy for the efficacy of ICI therapy in GI cancer and pancancer, indicating that the DRIA signature may serve as a powerful biomarker for guiding ICI therapy decisions.展开更多
目的:评估脂蛋白a水平与不同类型痴呆(阿尔茨海默病、路易体痴呆、额颞叶痴呆、帕金森病相关痴呆,血管性痴呆)发生风险之间相关性。方法:采用两样本孟德尔随机化研究方法,通过全基因组关联研究(genome-wide association study,GWAS)汇...目的:评估脂蛋白a水平与不同类型痴呆(阿尔茨海默病、路易体痴呆、额颞叶痴呆、帕金森病相关痴呆,血管性痴呆)发生风险之间相关性。方法:采用两样本孟德尔随机化研究方法,通过全基因组关联研究(genome-wide association study,GWAS)汇总数据集获得与脂蛋白a水平密切相关的遗传位点作为工具变量(IV),分别与不同类型痴呆进行两样本孟德尔随机化(TSMR)分析,以随机效应逆方差加权法(IVW)的结果为主。以MR-Egger法进行多效性分析、留一法进行敏感性分析来验证数据的可靠性。结果:脂蛋白a水平升高与路易体痴呆风险呈正相关(OR=1.68,P=0.0005),和阿尔茨海默病(Alzheimer's disease,AD)的发生呈负相关(OR=0.95,P=0.0027),与血管性痴呆、额颞叶痴呆、帕金森相关痴呆未发现明显相关性。结论:脂蛋白a水平可能与路易体痴呆发病风险呈正相关,可能与阿尔茨海默病发病风险呈负相关,与其它类型痴呆无明显相关性。展开更多
基金supported by the National Natural Science Foundation of China(31640001 and T2350005 to C.X.,U21A20148 to X.Z.and C.X.)Ministry of Science and Technology of China(2021ZD0140300 to C.X.)Presidential Foundation of Hefei Institutes of Physical Science,Chinese Academy of Sciences(Y96XC11131,E26CCG27,and E26CCD15 to C.X.,E36CWGBR24B and E36CZG14132 to T.C.)。
文摘Birds exhibit extraordinary mobility and remarkable navigational skills,obtaining guidance cues from the Earth’s magnetic field for orientation and long-distance movement.Bird species also show tremendous diversity in navigation strategies,with considerable differences even within the same taxa and among individuals from the same population.The highly conserved iron and iron-sulfur cluster binding magnetoreceptor(MagR)protein is suggested to enable animals,including birds,to detect the geomagnetic field and navigate accordingly.Notably,MagR is also implicated in other functions,such as electron transfer and biogenesis of iron-sulfur clusters,raising the question of whether variability exists in its biochemical and biophysical features among species,particularly birds.In the current study,we conducted a comparative analysis of MagR from two different bird species,including the migratory European robin(Erithacus rubecula)and the homing pigeon(Columba livia).Sequence alignment revealed an extremely high degree of similarity between the MagRs of these species,with only three sequence variations.Nevertheless,two of these variations underpinned significant differences in metal binding capacity,oligomeric state,and magnetic properties.These findings offer compelling evidence for the marked differences in MagR between the two avian species,potentially explaining how a highly conserved protein can mediate such diverse functions.
基金supported by the National Natural Science Foundation of China(31640001 and T2350005 to C.X.,U21A20148 to X.Z.and C.X.)Ministry of Science and Technology of China(2021ZD0140300 to C.X.)+2 种基金Natural Science Foundation of Hainan Province(No.822RC703 for J.L.)Foundation of Hainan Educational Committee(No.Hnky2022-27 for J.L.)Presidential Foundation of Hefei Institutes of Physical Science,Chinese Academy of Sciences(Y96XC11131,E26CCG27,and E26CCD15 to C.X.,E36CWGBR24B and E36CZG14132 to T.C.)。
文摘Iron-sulfur clusters(ISC)are essential cofactors for proteins involved in various biological processes,such as electron transport,biosynthetic reactions,DNA repair,and gene expression regulation.ISC assembly protein IscA1(or MagR)is found within the mitochondria of most eukaryotes.Magnetoreceptor(MagR)is a highly conserved A-type iron and iron-sulfur cluster-binding protein,characterized by two distinct types of iron-sulfur clusters,[2Fe-2S]and[3Fe-4S],each conferring unique magnetic properties.MagR forms a rod-like polymer structure in complex with photoreceptive cryptochrome(Cry)and serves as a putative magnetoreceptor for retrieving geomagnetic information in animal navigation.Although the N-terminal sequences of MagR vary among species,their specific function remains unknown.In the present study,we found that the N-terminal sequences of pigeon MagR,previously thought to serve as a mitochondrial targeting signal(MTS),were not cleaved following mitochondrial entry but instead modulated the efficiency with which iron-sulfur clusters and irons are bound.Moreover,the N-terminal region of MagR was required for the formation of a stable MagR/Cry complex.Thus,the N-terminal sequences in pigeon MagR fulfil more important functional roles than just mitochondrial targeting.These results further extend our understanding of the function of MagR and provide new insights into the origin of magnetoreception from an evolutionary perspective.
基金National Natural Science Foundation of China(31640001 and T2350005 to C.X.)Ministry of Science and Technology of China(2021ZD0140300 to C.X.)Presidential Foundation of Hefei Institutes of Physical Science,Chinese Academy of Sciences(Y96XC11131,E26CCG27,and E26CCD15 to C.X.,E36CWGBR24B and E36CZG14132 to T.C.)。
文摘Magnetic sense,or termed magnetoreception,has evolved in a broad range of taxa within the animal kingdom to facilitate orientation and navigation.MagRs,highly conserved A-type iron-sulfur proteins,are widely distributed across all phyla and play essential roles in both magnetoreception and iron-sulfur cluster biogenesis.However,the evolutionary origins and functional diversification of MagRs from their prokaryotic ancestor remain unclear.In this study,MagR sequences from 131 species,ranging from bacteria to humans,were selected for analysis,with 23 representative sequences covering species from prokaryotes to Mollusca,Arthropoda,Osteichthyes,Reptilia,Aves,and mammals chosen for protein expression and purification.Biochemical studies revealed a gradual increase in total iron content in MagRs during evolution.Three types of MagRs were identified,each with distinct iron and/or iron-sulfur cluster binding capacity and protein stability,indicating continuous expansion of the functional roles of MagRs during speciation and evolution.This evolutionary biochemical study provides valuable insights into how evolution shapes the physical and chemical properties of biological molecules such as MagRs and how these properties influence the evolutionary trajectories of MagRs.
基金the Cuiying Scientific and Technological Innovation Program of Lanzhou University Second Hospital,NO.CY2021-QNB09the Science and Technology Project of Gansu Province,NO.21JR11RA122+1 种基金Department of Education of Gansu Province:Innovation Fund Project,NO.2022B-056Gansu Province Clinical Research Center for Functional and Molecular Imaging,NO.21JR7RA438.
文摘BACKGROUND Diffusion-weighted imaging(DWI)has been developed to stage liver fibrosis.However,its diagnostic performance is inconsistent among studies.Therefore,it is worth studying the diagnostic value of various diffusion models for liver fibrosis in one cohort.AIM To evaluate the clinical potential of six diffusion-weighted models in liver fibrosis staging and compare their diagnostic performances.METHODS This prospective study enrolled 59 patients suspected of liver disease and scheduled for liver biopsy and 17 healthy participants.All participants underwent multi-b value DWI.The main DWI-derived parameters included Mono-apparent diffusion coefficient(ADC)from mono-exponential DWI,intravoxel incoherent motion model-derived true diffusion coefficient(IVIM-D),diffusion kurtosis imaging-derived apparent diffusivity(DKI-MD),stretched exponential model-derived distributed diffusion coefficient(SEM-DDC),fractional order calculus(FROC)model-derived diffusion coefficient(FROC-D)and FROC model-derived microstructural quantity(FROC-μ),and continuous-time random-walk(CTRW)model-derived anomalous diffusion coefficient(CTRW-D)and CTRW model-derived temporal diffusion heterogeneity index(CTRW-α).The correlations between DWI-derived parameters and fibrosis stages and the parameters’diagnostic efficacy in detecting significant fibrosis(SF)were assessed and compared.RESULTS CTRW-D(r=-0.356),CTRW-α(r=-0.297),DKI-MD(r=-0.297),FROC-D(r=-0.350),FROC-μ(r=-0.321),IVIM-D(r=-0.251),Mono-ADC(r=-0.362),and SEM-DDC(r=-0.263)were significantly correlated with fibrosis stages.The areas under the ROC curves(AUCs)of the combined index of the six models for distinguishing SF(0.697-0.747)were higher than each of the parameters alone(0.524-0.719).The DWI models’ability to detect SF was similar.The combined index of CTRW model parameters had the highest AUC(0.747).CONCLUSION The DWI models were similarly valuable in distinguishing SF in patients with liver disease.The combined index of CTRW parameters had the highest AUC.
文摘BACKGROUND Dilaceration is a rare dental developmental anomaly characterized by an abrupt deviation along the longitudinal axis of the root in which an angulation forms between the root and the crown.Here,we report on dilacerated bilateral maxi-llary central incisors in mixed dentition.CASE SUMMARY A 10-year-old girl presented with a chief complaint of unerupted central incisors.An oral examination and radiography provided the basis for a diagnosis of dilaceration of the maxillary central incisors.After surgical exposure of the impacted teeth,a button with an attached chain was applied to the palatal surface of teeth 11 and 21.After 8 mo,a button was bonded to the labial surface of the crown to fix an elastic chain and move the teeth toward the maxillary arch.Finally,a fixed appliance was applied to tooth alignment to Class 1 malocclusion using a 0.019×0.025-inch nickel-titanium wire.After 3 years of follow-up,the clinical findings and radiographic assessment showed that the roots had developed with vital dental pulp and healthy periodontium,were acceptable aesthetically,and showed no resorption.CONCLUSION The rare occurrences of dilacerated bilateral maxillary central incisors can be successfully treated through surgical exposure and orthodontics.
基金supported by the Earmarked Fund for CARS-12 from National Modern Agricultural Technology System.
文摘Five stems of rapeseed with abundant black microsclerotia were collected from Huangyuan County of Qinghai Province,China,and fungal isolates were obtained from the stems.They were identified based on morphology,molecular features and specific PCR detection.The results showed that the 10 fungal isolates belonged to Verticillium longisporum lineage A1/D3.One of the 10 isolates(HW7-1)was tested for virulence on three species of rapeseed,including B.napus Zhongshuang 9,B.rapa Qingyou 9 and B.juncea Tayou 2 by conidia inoculation of HW7-1 on roots of young seedlings.Control seedlings were inoculated with V.dahliae conidia or water alone.The seedlings of these treatments were transplanted in culture mix and incubated in a growth chamber(20℃).Results suggested that the control seedlings of three cultivars appeared quite healthy,while the seedlings inoculated with HW7-1 turned yellowing leaves,seedling stunting or even death after 22 days post-inoculation.V.longisporum was re-isolated from he yellow leaves,thus fulfilling Koch's postulates.Moreover,compared to the control treatments,inoculation with HW7-1 caused flowering delay and seed yield reduction on Tayou 2 with production of microsclerotia on the stems.To our knowledge,this is the first report of V.longisporum lineage A1/D3 on rapeseed in northwestern China.
基金supported by the National Key Research and Development Program of China,No.2021ZD0202503(to AHT)the National Natural Science Foundation of China,Nos.31872759(to AHT)and 32070707(to CF)+1 种基金Shenzhen Science and Technology Program,No.RCJC20210609104333007(to ZW)Shenzhen-Hong Kong Institute of Brain Science,Shenzhen Fundamental Research Institutions,No.2021SHIBS0002(to ZW).
文摘Morphological alterations in dendritic spines have been linked to changes in functional communication between neurons that affect learning and memory.Kinesin-4 KIF21A helps organize the microtubule-actin network at the cell cortex by interacting with KANK1;however,whether KIF21A modulates dendritic structure and function in neurons remains unknown.In this study,we found that KIF21A was distributed in a subset of dendritic spines,and that these KIF21A-positive spines were larger and more structurally plastic than KIF21A-negative spines.Furthermore,the interaction between KIF21A and KANK1 was found to be critical for dendritic spine morphogenesis and synaptic plasticity.Knockdown of either KIF21A or KANK1 inhibited dendritic spine morphogenesis and dendritic branching,and these deficits were fully rescued by coexpressing full-length KIF21A or KANK1,but not by proteins with mutations disrupting direct binding between KIF21A and KANK1 or binding between KANK1 and talin1.Knocking down KIF21A in the hippocampus of rats inhibited the amplitudes of long-term potentiation induced by high-frequency stimulation and negatively impacted the animals’cognitive abilities.Taken together,our findings demonstrate the function of KIF21A in modulating spine morphology and provide insight into its role in synaptic function.
基金financially supported by the National Key Research and Development Program of China(2018YFA0703003)National Natural Science Foundation of China(82072429,52125501,82371590)+6 种基金the Program for Innovation Team of Shaanxi Province(2023-CX-TD-17)the Key Research&Development Program of Shaanxi Province(2024SF-YBXM-355,2020SF-093,2021LLRH-08)the Natural Science Foundation of Henan Province(222300420358)the Postdoctoral Project of Shaanxi Province(2023BSHYDZZ30)the Postdoctoral Fellowship Program of CPSF(GZB20230573)the Institutional Foundation of the First Affiliated Hospital of Xi’an Jiaotong University(2019ZYTS-02)the Fundamental Research Funds for the Central Universities.
文摘The rotator cuff tear has emerged as a significant global health concern.However,existing therapies fail to fully restore the intricate bone-to-tendon gradients,resulting in compromised biomechanical functionalities of the reconstructed enthesis tissues.Herein,a tri-layered core–shell microfibrous scaffold with layer-specific growth factors(GFs)release is developed using coaxial electrohydrodynamic(EHD)printing for in situ cell recruitment and differentiation to facilitate gradient enthesis tissue repair.Stromal cell-derived factor-1(SDF-1)is loaded in the shell,while basic fibroblast GF,transforming GF-beta,and bone morphogenetic protein-2 are loaded in the core of the EHD-printed microfibrous scaffolds in a layer-specific manner.Correspondingly,the tri-layered microfibrous scaffolds have a core–shell fiber size of(25.7±5.1)μm,with a pore size sequentially increasing from(81.5±4.6)μm to(173.3±6.9)μm,and to(388.9±6.9μm)for the tenogenic,chondrogenic,and osteogenic instructive layers.A rapid release of embedded GFs is observed within the first 2 d,followed by a faster release of SDF-1 and a slightly slower release of differentiation GFs for approximately four weeks.The coaxial EHD-printed microfibrous scaffolds significantly promote stem cell recruitment and direct their differentiation toward tenocyte,chondrocyte,and osteocyte phenotypes in vitro.When implanted in vivo,the tri-layered core–shell microfibrous scaffolds rapidly restored the biomechanical functions and promoted enthesis tissue regeneration with native-like bone-to-tendon gradients.Our findings suggest that the microfibrous scaffolds with layer-specific GFs release may offer a promising clinical solution for enthesis regeneration.
基金supported by the National Natural Science Foundation of China(82271645)National Key Research and Development Program of China(2021YFC2700200 to F.S.)。
文摘Meiosis is a highly complex process significantly influenced by transcriptional regulation.However,studies on the mechanisms that govern transcriptomic changes during meiosis,especially in prophase I,are limited.Here,we performed single-cell ATAC-seq of human testis tissues and observed reprogramming during the transition from zygotene to pachytene spermatocytes.This event,conserved in mice,involved the deactivation of genes associated with meiosis after reprogramming and the activation of those related to spermatogenesis before their functional onset.Furthermore,we identified 282 transcriptional regulators(TRs)that underwent activation or deactivation subsequent to this process.Evidence suggested that physical contact signals from Sertoli cells may regulate these TRs in spermatocytes,while secreted ENHO signals may alter metabolic patterns in these cells.Our results further indicated that defective transcriptional reprogramming may be associated with non-obstructive azoospermia(NOA).This study revealed the importance of both physical contact and secreted signals between Sertoli cells and germ cells in meiotic progression.
基金supported by the National Key Research and Development Program (2022YFF0609504)the National Natural Science Foundation of China (61974126,51902273,62005230,62001405)the Natural Science Foundation of Fujian Province of China (No.2021J06009)
文摘Perovskite solar cells(PsCs)have developed tremendously over the past decade.However,the key factors influencing the power conversion efficiency(PCE)of PSCs remain incompletely understood,due to the complexity and coupling of these structural and compositional parameters.In this research,we demon-strate an effective approach to optimize PSCs performance via machine learning(ML).To address chal-lenges posed by limited samples,we propose a feature mask(FM)method,which augments training samples through feature transformation rather than synthetic data.Using this approach,squeeze-and-excitation residual network(SEResNet)model achieves an accuracy with a root-mean-square-error(RMSE)of 0.833%and a Pearson's correlation coefficient(r)of 0.980.Furthermore,we employ the permu-tation importance(PI)algorithm to investigate key features for PCE.Subsequently,we predict PCE through high-throughput screenings,in which we study the relationship between PCE and chemical com-positions.After that,we conduct experiments to validate the consistency between predicted results by ML and experimental results.In this work,ML demonstrates the capability to predict device performance,extract key parameters from complex systems,and accelerate the transition from laboratory findings to commercialapplications.
基金financial support from the Postgraduate Research & Practice Innovation Program of Jiangsu Province (KYCX24_0690)financial support from the National Natural Science Foundation of China (Project No. 22275088, 52101260)+4 种基金the Project of Shuangchuang Scholar of Jiangsu Province (Project No. JSSCBS20210212)the Fundamental Research Funds for the Central Universities (Project No. 30921011203)the Start-Up Grant (Project No. AE89991/340) from Nanjing University of Science and Technologyfinancial support from the Foundation of Jiangsu Educational Committee (22KJB310008)the Senior Talent Program of Jiangsu University (20JDG073)
文摘Ammonia(NH_(3))is an important raw material for modern agriculture and industry,being widely demanded to sustain the sustainable development of modern society.Currently,the industrial production methods of NH_(3),such as the traditional Haber-Bosch process,have drawbacks including high energy consumption and significant carbon dioxide emissions.In recent years,the electrocatalytic nitrate reduction reaction(NO_(3)RR)powered by intermittent renewable energy sources has gradually become a multidisciplinary research hotspot,as it allows for the efficient synthesis of NH_(3)under mild conditions.In this review,we focus on the research of electrocatalysts with atomic-level site,which have attracted attention due to their extremely high atomic utilization efficiency and unique structural characteristics in the field of NO_(3)RR.Firstly,we introduce the mechanism of nitrate reduction for ammonia synthesis and discuss the in-situ characterization techniques related to the mechanism study.Secondly,we review the progress of the electrocatalysts with atomic-level site for nitrate reduction and explore the structure-activity relationship to guide the rational design of efficient catalysts.Lastly,the conclusions of this review and the challenges and prospective of this promising field are presented.
基金the Key Scientific Research Projects of Henan Province to College Youth Backbone Teacher(No.2021118)the National Key Research and Development Program of China(No.2021YFE0112000)。
文摘Pyraclostrobin(PYR),a widely used fungicide,has negative effects on fish and algae,but its toxicity in protozoa remains unclear.In this study,the effects of PYR on the growth,oxidative stress,and gene expression related to stress and ATP-binding cassette(ABC)transporters in Tetrahymena thermophila were investigated.The result showed that the 96-h IC_(50)of PYR against T.thermophila was 17.2 mg/L.Moreover,PYR inhibited the growth of T.thermophila in concentration-or time-dependent manner.A morphological study revealed that the shape and size of T.thermophila changed,and damage of cell membrane surface was observed by scanning electron microscopy after 96 h of PYR exposure.The activities of superoxide dismutase(SOD)and catalase(CAT)increased throughout the experiment.In contrast,the glutathione(GSH)content was increased at 24 h and 48 h of exposure and decreased at 96 h.Moreover,a significant increase in malondialdehyde(MDA)level was observed in T.thermophila after96 h of exposure.Furthermore,PYR upregulated the HSP703,HSP705,GPx2,and ABAC15 gene expression in the 0.1–5-mg/L groups and downregulated the HSP704,HSP90,TGR,and ABCC52 mRNA levels at 96 h of exposure.These results suggest that PYR may exert adverse effects on T.thermophila by inducing oxidative stress and changing the gene expression related to ABC transporters and stress,which may enrich the understanding of the toxicity mechanism of PYR in aquatic organisms and provide reference data for aquatic ecological risk assessments.
基金the Fundamental Research Funds for the Central Universities,China(Grant No.:3332022147)the CAMS Innovation Fund for Medical Sciences,China(Grant Nos.:2021-I2M-1-071 and 2021-I2M-1-031)the National Natural Science Foundation of China(Grant No.:81872999).
文摘Zearalenone(ZEN)is a mycotoxin that extensively contaminates food and feed,posing a significant threat to public health.However,the mechanisms behind ZEN-induced intestinal immunotoxicity remain unclear.In this study,Sprague-Dawley(SD)rats were exposed to ZEN at a dosage of 5 mg/kg/day b.w.for a duration of 14 days.The results demonstrated that ZEN exposure led to notable pathological alterations and immunosuppression within the intestine.Furthermore,ZEN exposure caused a significant reduction in the levels of apolipoprotein E(ApoE)and liver X receptor(LXR)(P<0.05).Conversely,it upregulated the levels of myeloid-derived suppressor cells(MDSCs)markers(P<0.05)and decreased the presence of 27-hydroxycholesterol(27-HC)in the intestine(P<0.05).It was observed that ApoE or LXR agonists were able to mitigate the immunosuppressive effects induced by ZEN.Additionally,a bioinformatics analysis highlighted that the downregulation of ApoE might elevate the susceptibility to colorectal,breast,and lung cancers.These findings underscore the crucial role of the 27-HC/LXR/ApoE axis disruption in ZEN-induced MDSCs proliferation and subsequent inhibition of T lymphocyte activation within the rat intestine.Notably,ApoE may emerge as a pivotal target linking ZEN exposure to cancer development.
基金supported by the National Natural Science Foundation of China (Grant Nos. 81972761 and 82202837)the National Key R&D Program of China (Grant Nos. 2016YFC1303200 and 2022YFC2505100)。
文摘Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive accuracy of the DRIA signature for response to immune checkpoint inhibitor(ICI) therapy in gastrointestinal(GI) cancer.Methods: A DRIA signature was established based on two previously reported DNA damage immune response assays. Clinical and gene expression data from two published GI cancer cohorts were used to assess and validate the association between the DRIA score and response to ICI therapy. The predictive accuracy of the DRIA score was validated based on one ICI-treated melanoma and three pan-cancer published cohorts.Results: The DRIA signature includes three genes(CXCL10, IDO1, and IFI44L). In the discovery cancer cohort, DRIA-high patients with gastric cancer achieved a higher response rate to ICI therapy than DRIA-low patients(81.8% vs. 8.8%;P < 0.001), and the predictive accuracy of the DRIA score [area under the receiver operating characteristic curve(AUC) = 0.845] was superior to the predictive accuracy of PD-L1 expression, tumor mutational burden, microsatellite instability, and Epstein–Barr virus status. The validation cohort demonstrated that the DRIA score identified responders with microsatellite-stable colorectal and pancreatic adenocarcinoma who received dual PD-1 and CTLA-4 blockade with radiation therapy. Furthermore, the predictive performance of the DRIA score was shown to be robust through an extended validation in melanoma, urothelial cancer, and pan-cancer.Conclusions: The DRIA signature has superior and robust predictive accuracy for the efficacy of ICI therapy in GI cancer and pancancer, indicating that the DRIA signature may serve as a powerful biomarker for guiding ICI therapy decisions.
文摘目的:评估脂蛋白a水平与不同类型痴呆(阿尔茨海默病、路易体痴呆、额颞叶痴呆、帕金森病相关痴呆,血管性痴呆)发生风险之间相关性。方法:采用两样本孟德尔随机化研究方法,通过全基因组关联研究(genome-wide association study,GWAS)汇总数据集获得与脂蛋白a水平密切相关的遗传位点作为工具变量(IV),分别与不同类型痴呆进行两样本孟德尔随机化(TSMR)分析,以随机效应逆方差加权法(IVW)的结果为主。以MR-Egger法进行多效性分析、留一法进行敏感性分析来验证数据的可靠性。结果:脂蛋白a水平升高与路易体痴呆风险呈正相关(OR=1.68,P=0.0005),和阿尔茨海默病(Alzheimer's disease,AD)的发生呈负相关(OR=0.95,P=0.0027),与血管性痴呆、额颞叶痴呆、帕金森相关痴呆未发现明显相关性。结论:脂蛋白a水平可能与路易体痴呆发病风险呈正相关,可能与阿尔茨海默病发病风险呈负相关,与其它类型痴呆无明显相关性。
