BACKGROUND In this study,we retrospectively analysed macrophage infiltration and podocyte injury in three patients with diffuse proliferative lupus nephritis(LN)who un-derwent repeated renal biopsy.CASE SUMMARY Clinic...BACKGROUND In this study,we retrospectively analysed macrophage infiltration and podocyte injury in three patients with diffuse proliferative lupus nephritis(LN)who un-derwent repeated renal biopsy.CASE SUMMARY Clinical data of three diffuse proliferative LN patients with different pathological characteristics(case 1 was LN IV-G(A),case 2 was LN IV-G(A)+V,and case 3 was LN IV-G(A)+thrombotic microangiopathy)were reviewed.All patients underwent repeated renal biopsies 6 mo later,and renal biopsy specimens were studied.Macrophage infiltration was assessed by CD68 expression detected by immunohistochemical staining,and an immunofluorescence assay was used to detect podocin expression to assess podocyte damage.After treatment,Case 1 changed to LN III-(A),Case 2 remained as type V LN lesions,and Case 3,which changed to LN IV-S(A),had the worst prognosis.We observed reduced macro-phage infiltration after therapy.However,two of the patients with active lesions after treatment still showed macrophage infiltration in the renal interstitium.Before treatment,the three patients showed discontinuous expression of podocin.Notably,the integrity of podocin was restored after treatment in Case 1.CONCLUSION It may be possible to reverse podocyte damage and decrease the infiltrating ma-crophages in LN patients through effective treatment.展开更多
We have found that the expression of ring finger and WD repeat domain 3(RFWD3)is significantly higher in unpaired and paired hepatocellular carcinoma(HCC)tissues than in normal tissues.Moreover,this expression has a s...We have found that the expression of ring finger and WD repeat domain 3(RFWD3)is significantly higher in unpaired and paired hepatocellular carcinoma(HCC)tissues than in normal tissues.Moreover,this expression has a significant correlation with the infiltration level of 14 immune cell types and when the detected RFWD3 expression levels were grouped as high and low,a prominent difference was revealed for overall survival,disease-specific survival,and progression-free interval.Through statistical analysis(univariate Cox),we were also able to identify RFWD3 as an independent prognostic element for HCC,with RFWD3 having an ability to accurately predict HCC prognosis(area under the curve of 0.863).Finally,we have generated prognostic nomograms for probabilities of 1-,3-and 5-year overall survival in HCC via integrating the factors of age,pathologic stage,alpha-fetoprotein level,and RFWD3 expression.展开更多
The insect mitogenome is typically a compact circular molecule with highly conserved gene contents.Nonetheless,mitogenome structural variations have been reported in specific taxa,and gene rearrangements,usually the t...The insect mitogenome is typically a compact circular molecule with highly conserved gene contents.Nonetheless,mitogenome structural variations have been reported in specific taxa,and gene rearrangements,usually the tRNAs,occur in different lineages.Because synapomorphies of mitogenome organizations can provide information for phylogenetic inferences,comparative analyses of mitogenomes have been given increasing attention.However,most studies use a very few species to represent the whole genus,tribe,family,or even order,overlooking potential variations at lower taxonomic levels,which might lead to some incorrect inferences.To provide new insights into mitogenome organizations and their implications for phylogenetic inference,this study conducted comparative analyses for mitogenomes of three social bee tribes(Meliponini,Bombini,and Apini)based on the phylogenetic framework with denser taxonomic sampling at the species and population levels.Comparative analyses revealed that mitogenomes of Apini and Bombini are the typical type,while those of Meliponini show diverse variations in mitogenome sizes and organizations.Large inverted repeats(IRs)cause significant gene rearrangements of protein coding genes(PCGs)and rRNAs in Indo-Malay/Australian stingless bee species.Molecular evolution analyses showed that the lineage with IRs have lower dN/dS ratios for PCGs than lineages without IRs,indicating potential effects of IRs on the evolution of mitochondrial genes.The finding of IRs and different patterns of gene rearrangements suggested that Meliponini is a hotspot in mitogenome evolution.Unlike conserved PCGs and rRNAs whose rearrangements were found only in the mentioned lineages within Meliponini,tRNA rearrangements are common across all three tribes of social bees,and are significant even at the species level,indicating that comprehensive sampling is needed to fully understand the patterns of tRNA rearrangements,and their implications for phylogenetic inference.展开更多
Repeated blast impacts on personnel in explosive environments can exacerbate craniocerebral trauma.Most existing studies focus on the injury effects of a single blast,lacking in-depth analysis on the injury effects an...Repeated blast impacts on personnel in explosive environments can exacerbate craniocerebral trauma.Most existing studies focus on the injury effects of a single blast,lacking in-depth analysis on the injury effects and cumulative effects of repeated blasts.Therefore,rats were used as the experimental samples to suffer from explosion blasts with different peak air overpressures(167 kPa~482 kPa)and varying number of repeated blasts.The cumulative effect of craniocerebral trauma was most pronounced for moderate repeated blast,showing approximately 95%increase of trauma severity with penta blast,and an approximately 85%increase of trauma severity with penta minor blast.The cumulative effect of craniocerebral trauma from severe,repeated blast has a smaller rate of change compared to the other two conditions.The severity of trauma from penta blast increased by approximately 69%compared to a single blast.Comprehensive physiological,pathological and biochemical analysis show that the degree of neurological trauma caused by repeated blasts is higher than that of single blasts,and the pathological trauma to brain tissue is more extensive and severe.The trauma degree remains unchanged after double blast,increases by one grade after triple or quadruple blast,and increases by two grades after penta blast.展开更多
AIM:To assess the repeatability,interocular correlation,and agreement of quantitative swept-source optical coherence tomography angiography(OCTA)optic nerve head(ONH)parameters in healthy subjects.METHODS:Thir ty-thre...AIM:To assess the repeatability,interocular correlation,and agreement of quantitative swept-source optical coherence tomography angiography(OCTA)optic nerve head(ONH)parameters in healthy subjects.METHODS:Thir ty-three healthy subjects were enrolled.The ONH of both eyes were imaged four times by a swept-source-OCTA using a 3 mm×3 mm scanning protocol.Images of the radial peripapillary capillary were analyzed by a customized Matlab program,and the vessel density,fractal dimension,and vessel diameter index were measured.The repeatability of the four scans was determined by the intraclass correlation coefficient(ICC).The most well-centered optic disc from the four repeated scans was then selected for the interocular correlation and agreement analysis using the Pearson correlation coefficient,ICC and Bland-Altman plots.RESULTS:All swept-source-OCTA ONH parameters exhibited certain repeatability,with ICC>0.760 and coefficient of variation(CoV)≤7.301%.The obvious interocular correlation was observed for papillary vessel density(ICC=0.857),vessel diameter index(ICC=0.857)and fractal dimension(ICC=0.906),while circumpapillary vessel density exhibited moderate interocular correlation(ICC=0.687).Bland-Altman plots revealed an agreement range of-5.26%to 6.21%for circumpapillary vessel density.CONCLUSION:OCTA ONH parameters demonstrate good repeatability in healthy subjects.The interocular correlations of papillary vessel density,fractal dimension and vessel diameter index are high,but the correlation for circumpapillary vessel density is moderate.展开更多
Neurodegenerative diseases cause great medical and economic burdens for both patients and society;however, the complex molecular mechanisms thereof are not yet well understood. With the development of high-coverage se...Neurodegenerative diseases cause great medical and economic burdens for both patients and society;however, the complex molecular mechanisms thereof are not yet well understood. With the development of high-coverage sequencing technology, researchers have started to notice that genomic repeat regions, previously neglected in search of disease culprits, are active contributors to multiple neurodegenerative diseases. In this review, we describe the association between repeat element variants and multiple degenerative diseases through genome-wide association studies and targeted sequencing. We discuss the identification of disease-relevant repeat element variants, further powered by the advancement of long-read sequencing technologies and their related tools, and summarize recent findings in the molecular mechanisms of repeat element variants in brain degeneration, such as those causing transcriptional silencing or RNA-mediated gain of toxic function. Furthermore, we describe how in silico predictions using innovative computational models, such as deep learning language models, could enhance and accelerate our understanding of the functional impact of repeat element variants. Finally, we discuss future directions to advance current findings for a better understanding of neurodegenerative diseases and the clinical applications of genomic repeat elements.展开更多
BACKGROUND Thrombocytopenia 2,an autosomal dominant inherited disease characterized by moderate thrombocytopenia,predisposition to myeloid malignancies and normal platelet size and function,can be caused by 5’-untran...BACKGROUND Thrombocytopenia 2,an autosomal dominant inherited disease characterized by moderate thrombocytopenia,predisposition to myeloid malignancies and normal platelet size and function,can be caused by 5’-untranslated region(UTR)point mutations in ankyrin repeat domain containing 26(ANKRD26).Runt related transcription factor 1(RUNX1)and friend leukemia integration 1(FLI1)have been identified as negative regulators of ANKRD26.However,the positive regulators of ANKRD26 are still unknown.AIM To prove the positive regulatory effect of GATA binding protein 2(GATA2)on ANKRD26 transcription.METHODS Human induced pluripotent stem cells derived from bone marrow(hiPSC-BM)INTRODUCTION Ankyrin repeat domain containing protein 26(ANKRD26)acts as a regulator of adipogenesis and is involved in the regulation of feeding behavior[1-3].The ANKRD26 gene is located on chromosome 10 and shares regions of homology with the primate-specific gene family POTE.According to the Human Protein Atlas database,the ANKRD26 protein is localized to the Golgi apparatus and vesicles,and its expression can be detected in nearly all human tissues[4].Moreover,UniProt annotation revealed that ANKRD26 is localized in the centrosome and contains coiled-coil domains formed by spectrin helices and ankyrin repeats[5,6].The most common disease related to ANKRD26 is thrombocytopenia 2(THC2),which is a rare autosomal dominant inherited disease characterized by lifelong mild-to-moderate thrombocytopenia and mild bleeding[7-9].Caused by the variants in the 5’-untranslated region(UTR)of ANKRD26,THC2 is defined by a decrease in the number of platelets in circulating blood and results in increased bleeding and decreased clotting ability[8,10].Due to the point mutations that occur in the 5’-UTR of ANKRD26,its negative transcription factors(TFs),Runt related transcription factor 1(RUNX1)and friend leukemia integration 1(FLI1),lose their repression effect[11].The persistent expression of ANKRD26 increases the activity of the mitogen activated protein kinase and extracellular signal regulated kinase 1/2 signaling pathways,which are potentially involved in the regulation of thrombopoietin-dependent signaling and further impair proplatelet formation by megakaryocytes(MKs)[11].However,the positive regulators of ANKRD26,which might be associated with THC2 pathology,are still unknown.展开更多
This editorial summarizes the latest literature on the roles of neuronal PAS domain protein 2 and KN motif/ankyrin repeat domain 1 in type 2 diabetes(T2D).We highlight their involvement inβ-cell dysfunction,explore t...This editorial summarizes the latest literature on the roles of neuronal PAS domain protein 2 and KN motif/ankyrin repeat domain 1 in type 2 diabetes(T2D).We highlight their involvement inβ-cell dysfunction,explore their potential as therapeutic targets,and discuss the implications for new treatment strategies.We offer valuable insights into relevant gene regulation and cellular mechanisms relevant for the targeted management of T2D.展开更多
Cell lineages of nematodes are completely known: the adult male of Caenorhabditis elegans contains 1031 somatic cells, the hermaphrodite 959, not one more, not one less;cell divisions are strictly deterministic (as in...Cell lineages of nematodes are completely known: the adult male of Caenorhabditis elegans contains 1031 somatic cells, the hermaphrodite 959, not one more, not one less;cell divisions are strictly deterministic (as in the great majority of invertebrates) but so far nothing is known about the mechanism used by cells to count precise numbers of divisions. In vertebrates, each species has its invariable deterministic numbers of somites, vertebrae, fingers, and teeth: counting the number of iterations is a widespread process in living beings;nonetheless, it remains an unanswered question and a great challenge in cell biology. This paper introduces a computational model to investigate the possible role of satellite DNA in counting cell divisions, showing how cells may operate under Boolean logic algebra. Satellite DNA, made up of repeated monomers and subject to high epigenetic methylation rates, is very similar to iterable sequences used in programming: just like in the “iteration protocol” of algorithms, the epigenetic machinery may run over linear tandem repeats (that hold cell-fate data), read and orderly mark one monomer per cell-cycle (cytosine methylation), keep track and transmit marks to descendant cells, sending information to cell-cycle regulators.展开更多
AIM: To evaluate the repeatability of central corneal thickness (CCT) measurement by entacam, and agreement of CCT measured by Pentacam and ultrasound pachymetry (USP) in Chinese myopia. Thereby investigate the possib...AIM: To evaluate the repeatability of central corneal thickness (CCT) measurement by entacam, and agreement of CCT measured by Pentacam and ultrasound pachymetry (USP) in Chinese myopia. Thereby investigate the possibility of Pentacam as a substitute for USP in CCT measurement before refractive surgery. The effects of corneal curvature measured by Pentacam on CCT were also evaluated. METHODS: One hundred and forty-eight right eyes of 148 individual with myopia were included in this study. Three successive Pentacam CCT measurements followed by 10 successive ultrasound pachymetry were carried out in the 148 eyes. Mean of CCT taken by each device was calculated for comparison. According to the CCT measured by USP, all the 148 eyes were divided into 3 groups: <520 mu m, 520-560 mu m, >560 mu m. For all eyes and each group the CCT obtained by Pentacam and USP were compared. Anterior corneal curvature of the 148 eyes was also adopted for correlation analysis with CCT obtained by ultrasound pachymetry. In addition, CCT measurement using 60 random selected Scheimpflug images was performed by 3 skilled investigators at different time, and this was repeated for 3 times by a forth investigator to assess repeatability of Pentacam CCT measurement using Scheimpflug images. RESULTS: Intraclass correlation coefficient (ICC) analysis revealed high intraobserver repeatability (ICC=0.994, F=158.60, P<0.001) for CCT measurement by Pentacam. The interobserver (ICC=0.998, F =494.73, P <0.001) and intraobserver (ICC=0.997, F=383.98, P<0.001) repeatability for Pentacam CCT measurements using Scheimpflug images were also excellent. There was high positive correlation between the CCT values measured by Pentacam and ultrasound pachymetry (r=0.963, P<0.001). Bland-altman plots showed that the Pentacam underestimate the CCT by 8.02 mu m compared with ultrasouond pachymetry.The differences between Pentacam and USP increased as the CCT readings by USP increased (Pentacam vs USP: slope=-0.04, P< 0.05). The 95% upper and lower limits of agreement between CCT values obtained from the two devices were +9. 33 mu m and -25.37 mu m. No significant association could be found between CCT and anterior corneal curvature. CONCLUSION: Inter- and intraobserver variability for CCT measurements by Pentacam was considerably below clinically significant levels. CCT of myopia obtained by Scheimpflug camera, Pentacam, were highly correlated to that by ultrasound pachymetry. However, the values obtained are not directly interchangeable between Pentacam and ultrasound pachymetry as the 95% limits of agreement are relatively wide. Pentacam can be a useful instrument for measuring CCT in candidates to refractive surgery in clinic.展开更多
Very fast transient over-voltage （VFTO）, induced by disconnector operations in gas- insulated switchgears, has become the limiting dielectric stress at ultra-high voltage levels. Much work has been done to investiga...Very fast transient over-voltage （VFTO）, induced by disconnector operations in gas- insulated switchgears, has become the limiting dielectric stress at ultra-high voltage levels. Much work has been done to investigate single-strike waveforms of VFTO. However, little study has been carried out investigating the repeated strike process, which would influence VFTO significantly. In this paper, we carried out 450 effective experiments in an ultra-high voltage test circuit, and conducted calculations through the Monte Carlo simulation method, to investigate the repeated strike process. Firstly, the mechanism of the repeated strike process is proposed, based on the ex- perimentai results. Afterwards, statistical breakdown characteristics of disconnectors are obtained and analyzed. Finally, simulations of the repeated strike process are conducted, which indicate that the dielectric strength recovery speed and polarity effect factor have a joint effect on VFTO. This study enhances the understanding of the nature of VFTO, and may help to optimize the disconnector designed to minimize VFTO.展开更多
针对欠驱动机械臂系统的快速稳定控制中存在着的系统过程噪声和传感器观测噪声的干扰问题,设计了具有回路传输恢复的线性二次高斯(linear quadratic Gaussian control with loop transfer recovery, LQG/LTR)控制器。该控制器由卡尔曼...针对欠驱动机械臂系统的快速稳定控制中存在着的系统过程噪声和传感器观测噪声的干扰问题,设计了具有回路传输恢复的线性二次高斯(linear quadratic Gaussian control with loop transfer recovery, LQG/LTR)控制器。该控制器由卡尔曼滤波器和最优状态反馈增益调节器两部分组成,并进一步使用了回路传输恢复技术提高了控制系统稳定裕度。仿真试验表明:LQG/LTR控制方法相比于线性二次型调节器控制方法具有更加出色的动态品质,能很好地抑制噪声造成的系统不稳定问题,使得机械臂快速稳定在期望位置,具备良好的稳定性和鲁棒性。展开更多
OBJECT:Progression of infiltrative low-grade gliomas(LGGs)has been reported previously.The limitations ofsuch studies include diverse histological grading systems,intervening therapy,and the lack of histological confi...OBJECT:Progression of infiltrative low-grade gliomas(LGGs)has been reported previously.The limitations ofsuch studies include diverse histological grading systems,intervening therapy,and the lack of histological confir-mation of malignant tumor progression.The aim of this study was to determine tumor progression in adult patientswith an initial diagnosis of infiltrative LGG who subsequently underwent a repeated operation,but no other inter-vening therapy.The authors examined factors that may be associated with tumor progression.展开更多
The Oriental Stork(Ciconia boyciana)is listed as'Endangered'on the International Union for the Conservation of Nature(IUCN)Red List of Threatened Species and is classified as a first category nationally protec...The Oriental Stork(Ciconia boyciana)is listed as'Endangered'on the International Union for the Conservation of Nature(IUCN)Red List of Threatened Species and is classified as a first category nationally protected bird species in China.Understanding this species'seasonal movements and migration will facilitate effective conservation to promote its population.We tagged 27 Oriental Stork nestlings at Xingkai Lake on the Sanjiang Plain in Heilongjiang Province,China,used GPS tracking to follow them over the periods of 2014-2017 and 2019-2022,and confirmed their detailed migratory routes using the spatial analysis function of ArcGIS 10.7.We discovered four migration routes during autumn migration:one common long-distance migration route in which the storks migrated along the coastline of Bohai Bay to the middle and lower reaches of the Yangtze River for wintering,one short-distance migration route in which the storks wintered in Bohai Bay and two other migration routes in which the storks crossed the Bohai Strait around the Yellow River and wintered in South Korea.There were no significant differences in the number of migration days,residence days,migration distances,number of stopovers and average number of days spent at stopover sites between the autumn and spring migrations(P>0.05).However,the storks migrated significantly faster in spring than in autumn(P=0.03).The same individuals did not exhibit a high degree of repetition in their migration timing and route selection in either autumn or spring migration.Even storks from the same nest exhibited considerable between-individual variation in their migration routes.Some important stopover sites were identified,especially in the Bohai Rim Region and on the Songnen Plain,and we further explored the current conservation status at these two important sites.Overall,our results contribute to the understanding of the annual migration,dispersal and protection status of the endangered Oriental Stork and provide a scientific basis for conservation decisions and the development of action plans for this species.展开更多
AIM:To report the myopia-controlling effect of repeated low-level red-light(RLRL)therapy in patients with Stickler syndrome(STL),an inherited collagenic disease typically presenting with early onset myopia.METHODS:Thr...AIM:To report the myopia-controlling effect of repeated low-level red-light(RLRL)therapy in patients with Stickler syndrome(STL),an inherited collagenic disease typically presenting with early onset myopia.METHODS:Three STL children,aged 3,7,and 11y,received RLRL therapy throughout the follow-up period of 17,3,and 6mo,respectively after exclusion of fundus anomalies.Data on best-corrected visual acuity(BCVA),intraocular pressure,cycloplegic subjective refraction,ocular biometrics,scanning laser ophthalmoscope,optical coherence tomography,genetic testing,systemic disease history,and family history were recorded.RESULTS:At the initiation of the RLRL therapy,the spherical equivalent(SE)of 6 eyes from 3 patients ranged from-3.75 to-20.38 D,axial length(AL)were from 23.88 to 30.68 mm,and BCVA were from 0.4 to 1.0(decimal notation).Myopia progression of all six eyes slowed down after RLRL therapy.AL in five out of the six eyes shortened-0.07 to-0.63 mm.No side effects were observed.CONCLUSION:Three cases of STL whose progression of myopic shift and AL elongation are successfully reduced and even reversed after RLRL therapy.展开更多
In higher plants, the chloroplast is the most important organelle for photosynthesis and for numerous essential metabolic processes in the cell. Although many genes involved in chloroplast development have been identi...In higher plants, the chloroplast is the most important organelle for photosynthesis and for numerous essential metabolic processes in the cell. Although many genes involved in chloroplast development have been identified, the mechanisms underlying such development are not fully understood. In this study, a rice(Oryza sativa) mutant exhibiting pale green color and seedling lethality was isolated from a mutant library. The mutated gene was identified as an ortholog of THA8(thylakoid assembly 8) in Arabidopsis and maize. This gene is designated as OsTHA8 hereafter. OsTHA8 showed a typical pentatricopeptide repeat(PPR) characteristic of only four PPR motifs. Inactivation of OsTHA8 led to a deficiency in chloroplast development in the rice seedling stage. OsTHA8 was expressed mainly in young leaves and leaf sheaths.The OsTHA8 protein was localized to the chloroplast. Loss of function of OsTHA8 weakened the editing efficiency of ndhB-611/737 and rps8-182 transcripts under normal conditions. Y2H and BiFC indicated that OsTHA8 facilitates RNA editing by forming an editosome with multiple organellar RNA editing factor(OsMORF8) and thioredoxin z(OsTRXz), which function in RNA editing in rice chloroplasts. Defective OsTHA8 impaired chloroplast ribosome assembly and resulted in reduced expression of PEP-dependent genes and photosynthesis-related genes. Abnormal splicing of the chloroplast gene ycf3 was detected in ostha8. These findings reveal a synergistic regulatory mechanism of chloroplast biogenesis mediated by RNA, broaden the function of the PPR family, and shed light on the RNA editing complex in rice.展开更多
Every breeding program that aims to create new and improved cultivars with desired traits mostly relies on information related to genetic diversity.Therefore,molecular characterization of germplasms is important to ob...Every breeding program that aims to create new and improved cultivars with desired traits mostly relies on information related to genetic diversity.Therefore,molecular characterization of germplasms is important to obtain target cultivars with desirable traits.Sweet potato[Ipomoea batatas(L.)Lam]is widely considered the world’s most important crop,with great diversity in morphological and phenotypic traits.The genetic diversity of 20 sweet potato germplasms originating from Bangladesh,CIP,Philippines,Taiwan,and Malaysia were compared,which was accomplished by genetic diversity analysis by exploring 20 microsatellite DNA markers for germplasm characterization and utilization.This information was effective in differentiating or clustering the sweet potato genotypes.A total of 64 alleles were generated using the 20 primers throughout the 20 germplasm samples,with locus IBS97 having the highest number of alleles(5),whereas locus IbU33 had the fewest alleles(2).The alleles varied in size from 105(IbU31)to 213 base pairs(IBS34).The Polymorphism Information Content(PIC)values for the loci IbL46 and IBS97 varied from 0.445 to 0.730.IBS97 has the highest number of effective alleles(3.704),compared to an average of 2.520.The average Shannon’s diversity index(H)was 1.003,ranging from 0.673 in IbU3 to 1.432 in IBS97.The value of gene flow(Nm)varied between 0.000 and 0.005,with an average of 0.003,whereas genetic differentiation(FST-values)ranged between 0.901 and 1.000.The sweet potato germplasm included in this study had a broad genetic base.SP1 vs.SP9 and SP12 vs.SP18 germplasm pairings had the greatest genetic distance(GD=0.965),while SP1 vs.SP2 germplasm couples had the least genetic diversity(GD=0.093).Twenty genotypes were classified into two groups in the UPGMA dendrogram,with 16 genotypes classified as group“A”and the remaining four genotypes,SP10,SP18,SP19,and SP20,classified as group“B.”According to cluster analysis,the anticipated heterozygosity(gene diversity)of Nei(1973)was 0.591 on average.In summary,SSR markers successfully evaluated the genetic relationships among the sweet potato accessions used and generated a high level of polymorphism.The results of the present study will be useful for the management of germplasm,improvement of the current breeding strategies,and the release of new cultivars as varieties.展开更多
基金Supported by National Natural Science Foundation of China,No.81960136the Science and Technology Department of Yunnan Province,No.202101AT070243.
文摘BACKGROUND In this study,we retrospectively analysed macrophage infiltration and podocyte injury in three patients with diffuse proliferative lupus nephritis(LN)who un-derwent repeated renal biopsy.CASE SUMMARY Clinical data of three diffuse proliferative LN patients with different pathological characteristics(case 1 was LN IV-G(A),case 2 was LN IV-G(A)+V,and case 3 was LN IV-G(A)+thrombotic microangiopathy)were reviewed.All patients underwent repeated renal biopsies 6 mo later,and renal biopsy specimens were studied.Macrophage infiltration was assessed by CD68 expression detected by immunohistochemical staining,and an immunofluorescence assay was used to detect podocin expression to assess podocyte damage.After treatment,Case 1 changed to LN III-(A),Case 2 remained as type V LN lesions,and Case 3,which changed to LN IV-S(A),had the worst prognosis.We observed reduced macro-phage infiltration after therapy.However,two of the patients with active lesions after treatment still showed macrophage infiltration in the renal interstitium.Before treatment,the three patients showed discontinuous expression of podocin.Notably,the integrity of podocin was restored after treatment in Case 1.CONCLUSION It may be possible to reverse podocyte damage and decrease the infiltrating ma-crophages in LN patients through effective treatment.
文摘We have found that the expression of ring finger and WD repeat domain 3(RFWD3)is significantly higher in unpaired and paired hepatocellular carcinoma(HCC)tissues than in normal tissues.Moreover,this expression has a significant correlation with the infiltration level of 14 immune cell types and when the detected RFWD3 expression levels were grouped as high and low,a prominent difference was revealed for overall survival,disease-specific survival,and progression-free interval.Through statistical analysis(univariate Cox),we were also able to identify RFWD3 as an independent prognostic element for HCC,with RFWD3 having an ability to accurately predict HCC prognosis(area under the curve of 0.863).Finally,we have generated prognostic nomograms for probabilities of 1-,3-and 5-year overall survival in HCC via integrating the factors of age,pathologic stage,alpha-fetoprotein level,and RFWD3 expression.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB31000000)Science and Technology Basic Resources Investigation Program of China(2021FY100200)+1 种基金Yunnan Revitalization Talent Support Program“Young Talent”and"Innovation Team"Projectsthe 14th Five-Year Plan of Xishuangbanna Tropical Botanical Garden,Chinese Academy of Science(XTBG-1450101)。
文摘The insect mitogenome is typically a compact circular molecule with highly conserved gene contents.Nonetheless,mitogenome structural variations have been reported in specific taxa,and gene rearrangements,usually the tRNAs,occur in different lineages.Because synapomorphies of mitogenome organizations can provide information for phylogenetic inferences,comparative analyses of mitogenomes have been given increasing attention.However,most studies use a very few species to represent the whole genus,tribe,family,or even order,overlooking potential variations at lower taxonomic levels,which might lead to some incorrect inferences.To provide new insights into mitogenome organizations and their implications for phylogenetic inference,this study conducted comparative analyses for mitogenomes of three social bee tribes(Meliponini,Bombini,and Apini)based on the phylogenetic framework with denser taxonomic sampling at the species and population levels.Comparative analyses revealed that mitogenomes of Apini and Bombini are the typical type,while those of Meliponini show diverse variations in mitogenome sizes and organizations.Large inverted repeats(IRs)cause significant gene rearrangements of protein coding genes(PCGs)and rRNAs in Indo-Malay/Australian stingless bee species.Molecular evolution analyses showed that the lineage with IRs have lower dN/dS ratios for PCGs than lineages without IRs,indicating potential effects of IRs on the evolution of mitochondrial genes.The finding of IRs and different patterns of gene rearrangements suggested that Meliponini is a hotspot in mitogenome evolution.Unlike conserved PCGs and rRNAs whose rearrangements were found only in the mentioned lineages within Meliponini,tRNA rearrangements are common across all three tribes of social bees,and are significant even at the species level,indicating that comprehensive sampling is needed to fully understand the patterns of tRNA rearrangements,and their implications for phylogenetic inference.
基金supported by the National Natural Science Foundation of China(Grant No.12372356)Postgraduate Scientific Research In-novation Project of Hunan Province(Grant No.CX20221044).
文摘Repeated blast impacts on personnel in explosive environments can exacerbate craniocerebral trauma.Most existing studies focus on the injury effects of a single blast,lacking in-depth analysis on the injury effects and cumulative effects of repeated blasts.Therefore,rats were used as the experimental samples to suffer from explosion blasts with different peak air overpressures(167 kPa~482 kPa)and varying number of repeated blasts.The cumulative effect of craniocerebral trauma was most pronounced for moderate repeated blast,showing approximately 95%increase of trauma severity with penta blast,and an approximately 85%increase of trauma severity with penta minor blast.The cumulative effect of craniocerebral trauma from severe,repeated blast has a smaller rate of change compared to the other two conditions.The severity of trauma from penta blast increased by approximately 69%compared to a single blast.Comprehensive physiological,pathological and biochemical analysis show that the degree of neurological trauma caused by repeated blasts is higher than that of single blasts,and the pathological trauma to brain tissue is more extensive and severe.The trauma degree remains unchanged after double blast,increases by one grade after triple or quadruple blast,and increases by two grades after penta blast.
基金Natural Science Foundation of Guangdong Province(No.2018A0303130306)Shantou Science and Technology Program(No.190917085269835,No.200629165261641).
文摘AIM:To assess the repeatability,interocular correlation,and agreement of quantitative swept-source optical coherence tomography angiography(OCTA)optic nerve head(ONH)parameters in healthy subjects.METHODS:Thir ty-three healthy subjects were enrolled.The ONH of both eyes were imaged four times by a swept-source-OCTA using a 3 mm×3 mm scanning protocol.Images of the radial peripapillary capillary were analyzed by a customized Matlab program,and the vessel density,fractal dimension,and vessel diameter index were measured.The repeatability of the four scans was determined by the intraclass correlation coefficient(ICC).The most well-centered optic disc from the four repeated scans was then selected for the interocular correlation and agreement analysis using the Pearson correlation coefficient,ICC and Bland-Altman plots.RESULTS:All swept-source-OCTA ONH parameters exhibited certain repeatability,with ICC>0.760 and coefficient of variation(CoV)≤7.301%.The obvious interocular correlation was observed for papillary vessel density(ICC=0.857),vessel diameter index(ICC=0.857)and fractal dimension(ICC=0.906),while circumpapillary vessel density exhibited moderate interocular correlation(ICC=0.687).Bland-Altman plots revealed an agreement range of-5.26%to 6.21%for circumpapillary vessel density.CONCLUSION:OCTA ONH parameters demonstrate good repeatability in healthy subjects.The interocular correlations of papillary vessel density,fractal dimension and vessel diameter index are high,but the correlation for circumpapillary vessel density is moderate.
基金supported by the National Natural Science Foundation of China, No.61932008Natural Science Foundation of Shanghai, No.21ZR1403200 (both to JC)。
文摘Neurodegenerative diseases cause great medical and economic burdens for both patients and society;however, the complex molecular mechanisms thereof are not yet well understood. With the development of high-coverage sequencing technology, researchers have started to notice that genomic repeat regions, previously neglected in search of disease culprits, are active contributors to multiple neurodegenerative diseases. In this review, we describe the association between repeat element variants and multiple degenerative diseases through genome-wide association studies and targeted sequencing. We discuss the identification of disease-relevant repeat element variants, further powered by the advancement of long-read sequencing technologies and their related tools, and summarize recent findings in the molecular mechanisms of repeat element variants in brain degeneration, such as those causing transcriptional silencing or RNA-mediated gain of toxic function. Furthermore, we describe how in silico predictions using innovative computational models, such as deep learning language models, could enhance and accelerate our understanding of the functional impact of repeat element variants. Finally, we discuss future directions to advance current findings for a better understanding of neurodegenerative diseases and the clinical applications of genomic repeat elements.
基金Supported by General Program of National Natural Science Foundation of China,No.81770197Scientific and Technological Research Major Program of Chongqing Municipal Education Commission,No.KJZD-M202312802+1 种基金Chongqing Natural Science Foundation of China,No.CSTB2022NSCQ-MSX0190,No.CSTB2022NSCQ-MSX0176,and No.cstc2020jcyj-msxmX0051Xinqiao Young Postdoc Talent Incubation Program,No.2022YQB098.
文摘BACKGROUND Thrombocytopenia 2,an autosomal dominant inherited disease characterized by moderate thrombocytopenia,predisposition to myeloid malignancies and normal platelet size and function,can be caused by 5’-untranslated region(UTR)point mutations in ankyrin repeat domain containing 26(ANKRD26).Runt related transcription factor 1(RUNX1)and friend leukemia integration 1(FLI1)have been identified as negative regulators of ANKRD26.However,the positive regulators of ANKRD26 are still unknown.AIM To prove the positive regulatory effect of GATA binding protein 2(GATA2)on ANKRD26 transcription.METHODS Human induced pluripotent stem cells derived from bone marrow(hiPSC-BM)INTRODUCTION Ankyrin repeat domain containing protein 26(ANKRD26)acts as a regulator of adipogenesis and is involved in the regulation of feeding behavior[1-3].The ANKRD26 gene is located on chromosome 10 and shares regions of homology with the primate-specific gene family POTE.According to the Human Protein Atlas database,the ANKRD26 protein is localized to the Golgi apparatus and vesicles,and its expression can be detected in nearly all human tissues[4].Moreover,UniProt annotation revealed that ANKRD26 is localized in the centrosome and contains coiled-coil domains formed by spectrin helices and ankyrin repeats[5,6].The most common disease related to ANKRD26 is thrombocytopenia 2(THC2),which is a rare autosomal dominant inherited disease characterized by lifelong mild-to-moderate thrombocytopenia and mild bleeding[7-9].Caused by the variants in the 5’-untranslated region(UTR)of ANKRD26,THC2 is defined by a decrease in the number of platelets in circulating blood and results in increased bleeding and decreased clotting ability[8,10].Due to the point mutations that occur in the 5’-UTR of ANKRD26,its negative transcription factors(TFs),Runt related transcription factor 1(RUNX1)and friend leukemia integration 1(FLI1),lose their repression effect[11].The persistent expression of ANKRD26 increases the activity of the mitogen activated protein kinase and extracellular signal regulated kinase 1/2 signaling pathways,which are potentially involved in the regulation of thrombopoietin-dependent signaling and further impair proplatelet formation by megakaryocytes(MKs)[11].However,the positive regulators of ANKRD26,which might be associated with THC2 pathology,are still unknown.
文摘This editorial summarizes the latest literature on the roles of neuronal PAS domain protein 2 and KN motif/ankyrin repeat domain 1 in type 2 diabetes(T2D).We highlight their involvement inβ-cell dysfunction,explore their potential as therapeutic targets,and discuss the implications for new treatment strategies.We offer valuable insights into relevant gene regulation and cellular mechanisms relevant for the targeted management of T2D.
文摘Cell lineages of nematodes are completely known: the adult male of Caenorhabditis elegans contains 1031 somatic cells, the hermaphrodite 959, not one more, not one less;cell divisions are strictly deterministic (as in the great majority of invertebrates) but so far nothing is known about the mechanism used by cells to count precise numbers of divisions. In vertebrates, each species has its invariable deterministic numbers of somites, vertebrae, fingers, and teeth: counting the number of iterations is a widespread process in living beings;nonetheless, it remains an unanswered question and a great challenge in cell biology. This paper introduces a computational model to investigate the possible role of satellite DNA in counting cell divisions, showing how cells may operate under Boolean logic algebra. Satellite DNA, made up of repeated monomers and subject to high epigenetic methylation rates, is very similar to iterable sequences used in programming: just like in the “iteration protocol” of algorithms, the epigenetic machinery may run over linear tandem repeats (that hold cell-fate data), read and orderly mark one monomer per cell-cycle (cytosine methylation), keep track and transmit marks to descendant cells, sending information to cell-cycle regulators.
文摘AIM: To evaluate the repeatability of central corneal thickness (CCT) measurement by entacam, and agreement of CCT measured by Pentacam and ultrasound pachymetry (USP) in Chinese myopia. Thereby investigate the possibility of Pentacam as a substitute for USP in CCT measurement before refractive surgery. The effects of corneal curvature measured by Pentacam on CCT were also evaluated. METHODS: One hundred and forty-eight right eyes of 148 individual with myopia were included in this study. Three successive Pentacam CCT measurements followed by 10 successive ultrasound pachymetry were carried out in the 148 eyes. Mean of CCT taken by each device was calculated for comparison. According to the CCT measured by USP, all the 148 eyes were divided into 3 groups: <520 mu m, 520-560 mu m, >560 mu m. For all eyes and each group the CCT obtained by Pentacam and USP were compared. Anterior corneal curvature of the 148 eyes was also adopted for correlation analysis with CCT obtained by ultrasound pachymetry. In addition, CCT measurement using 60 random selected Scheimpflug images was performed by 3 skilled investigators at different time, and this was repeated for 3 times by a forth investigator to assess repeatability of Pentacam CCT measurement using Scheimpflug images. RESULTS: Intraclass correlation coefficient (ICC) analysis revealed high intraobserver repeatability (ICC=0.994, F=158.60, P<0.001) for CCT measurement by Pentacam. The interobserver (ICC=0.998, F =494.73, P <0.001) and intraobserver (ICC=0.997, F=383.98, P<0.001) repeatability for Pentacam CCT measurements using Scheimpflug images were also excellent. There was high positive correlation between the CCT values measured by Pentacam and ultrasound pachymetry (r=0.963, P<0.001). Bland-altman plots showed that the Pentacam underestimate the CCT by 8.02 mu m compared with ultrasouond pachymetry.The differences between Pentacam and USP increased as the CCT readings by USP increased (Pentacam vs USP: slope=-0.04, P< 0.05). The 95% upper and lower limits of agreement between CCT values obtained from the two devices were +9. 33 mu m and -25.37 mu m. No significant association could be found between CCT and anterior corneal curvature. CONCLUSION: Inter- and intraobserver variability for CCT measurements by Pentacam was considerably below clinically significant levels. CCT of myopia obtained by Scheimpflug camera, Pentacam, were highly correlated to that by ultrasound pachymetry. However, the values obtained are not directly interchangeable between Pentacam and ultrasound pachymetry as the 95% limits of agreement are relatively wide. Pentacam can be a useful instrument for measuring CCT in candidates to refractive surgery in clinic.
基金supported in part by National Natural Science Foundation of China(No.51277106)in part by the National Basic Research Program of China(973 Program)(No.2011CB209405)
文摘Very fast transient over-voltage （VFTO）, induced by disconnector operations in gas- insulated switchgears, has become the limiting dielectric stress at ultra-high voltage levels. Much work has been done to investigate single-strike waveforms of VFTO. However, little study has been carried out investigating the repeated strike process, which would influence VFTO significantly. In this paper, we carried out 450 effective experiments in an ultra-high voltage test circuit, and conducted calculations through the Monte Carlo simulation method, to investigate the repeated strike process. Firstly, the mechanism of the repeated strike process is proposed, based on the ex- perimentai results. Afterwards, statistical breakdown characteristics of disconnectors are obtained and analyzed. Finally, simulations of the repeated strike process are conducted, which indicate that the dielectric strength recovery speed and polarity effect factor have a joint effect on VFTO. This study enhances the understanding of the nature of VFTO, and may help to optimize the disconnector designed to minimize VFTO.
文摘针对欠驱动机械臂系统的快速稳定控制中存在着的系统过程噪声和传感器观测噪声的干扰问题,设计了具有回路传输恢复的线性二次高斯(linear quadratic Gaussian control with loop transfer recovery, LQG/LTR)控制器。该控制器由卡尔曼滤波器和最优状态反馈增益调节器两部分组成,并进一步使用了回路传输恢复技术提高了控制系统稳定裕度。仿真试验表明:LQG/LTR控制方法相比于线性二次型调节器控制方法具有更加出色的动态品质,能很好地抑制噪声造成的系统不稳定问题,使得机械臂快速稳定在期望位置,具备良好的稳定性和鲁棒性。
文摘OBJECT:Progression of infiltrative low-grade gliomas(LGGs)has been reported previously.The limitations ofsuch studies include diverse histological grading systems,intervening therapy,and the lack of histological confir-mation of malignant tumor progression.The aim of this study was to determine tumor progression in adult patientswith an initial diagnosis of infiltrative LGG who subsequently underwent a repeated operation,but no other inter-vening therapy.The authors examined factors that may be associated with tumor progression.
基金supported by National Key Research and Development Program of China(No.2019YFA0607103)the National Forestry and Grassland Administration of China(91217-2022,202999922001,213023721203)。
文摘The Oriental Stork(Ciconia boyciana)is listed as'Endangered'on the International Union for the Conservation of Nature(IUCN)Red List of Threatened Species and is classified as a first category nationally protected bird species in China.Understanding this species'seasonal movements and migration will facilitate effective conservation to promote its population.We tagged 27 Oriental Stork nestlings at Xingkai Lake on the Sanjiang Plain in Heilongjiang Province,China,used GPS tracking to follow them over the periods of 2014-2017 and 2019-2022,and confirmed their detailed migratory routes using the spatial analysis function of ArcGIS 10.7.We discovered four migration routes during autumn migration:one common long-distance migration route in which the storks migrated along the coastline of Bohai Bay to the middle and lower reaches of the Yangtze River for wintering,one short-distance migration route in which the storks wintered in Bohai Bay and two other migration routes in which the storks crossed the Bohai Strait around the Yellow River and wintered in South Korea.There were no significant differences in the number of migration days,residence days,migration distances,number of stopovers and average number of days spent at stopover sites between the autumn and spring migrations(P>0.05).However,the storks migrated significantly faster in spring than in autumn(P=0.03).The same individuals did not exhibit a high degree of repetition in their migration timing and route selection in either autumn or spring migration.Even storks from the same nest exhibited considerable between-individual variation in their migration routes.Some important stopover sites were identified,especially in the Bohai Rim Region and on the Songnen Plain,and we further explored the current conservation status at these two important sites.Overall,our results contribute to the understanding of the annual migration,dispersal and protection status of the endangered Oriental Stork and provide a scientific basis for conservation decisions and the development of action plans for this species.
文摘AIM:To report the myopia-controlling effect of repeated low-level red-light(RLRL)therapy in patients with Stickler syndrome(STL),an inherited collagenic disease typically presenting with early onset myopia.METHODS:Three STL children,aged 3,7,and 11y,received RLRL therapy throughout the follow-up period of 17,3,and 6mo,respectively after exclusion of fundus anomalies.Data on best-corrected visual acuity(BCVA),intraocular pressure,cycloplegic subjective refraction,ocular biometrics,scanning laser ophthalmoscope,optical coherence tomography,genetic testing,systemic disease history,and family history were recorded.RESULTS:At the initiation of the RLRL therapy,the spherical equivalent(SE)of 6 eyes from 3 patients ranged from-3.75 to-20.38 D,axial length(AL)were from 23.88 to 30.68 mm,and BCVA were from 0.4 to 1.0(decimal notation).Myopia progression of all six eyes slowed down after RLRL therapy.AL in five out of the six eyes shortened-0.07 to-0.63 mm.No side effects were observed.CONCLUSION:Three cases of STL whose progression of myopic shift and AL elongation are successfully reduced and even reversed after RLRL therapy.
基金supported by the Natural Science Foundation of Hebei Province (C2021208014)the Key R&D Program of Hebei Province (22326312D, 21326332D)。
文摘In higher plants, the chloroplast is the most important organelle for photosynthesis and for numerous essential metabolic processes in the cell. Although many genes involved in chloroplast development have been identified, the mechanisms underlying such development are not fully understood. In this study, a rice(Oryza sativa) mutant exhibiting pale green color and seedling lethality was isolated from a mutant library. The mutated gene was identified as an ortholog of THA8(thylakoid assembly 8) in Arabidopsis and maize. This gene is designated as OsTHA8 hereafter. OsTHA8 showed a typical pentatricopeptide repeat(PPR) characteristic of only four PPR motifs. Inactivation of OsTHA8 led to a deficiency in chloroplast development in the rice seedling stage. OsTHA8 was expressed mainly in young leaves and leaf sheaths.The OsTHA8 protein was localized to the chloroplast. Loss of function of OsTHA8 weakened the editing efficiency of ndhB-611/737 and rps8-182 transcripts under normal conditions. Y2H and BiFC indicated that OsTHA8 facilitates RNA editing by forming an editosome with multiple organellar RNA editing factor(OsMORF8) and thioredoxin z(OsTRXz), which function in RNA editing in rice chloroplasts. Defective OsTHA8 impaired chloroplast ribosome assembly and resulted in reduced expression of PEP-dependent genes and photosynthesis-related genes. Abnormal splicing of the chloroplast gene ycf3 was detected in ostha8. These findings reveal a synergistic regulatory mechanism of chloroplast biogenesis mediated by RNA, broaden the function of the PPR family, and shed light on the RNA editing complex in rice.
基金The work was financially supported by National Agricultural Technology Program-II Project(NATP-2)BARC Component Bangladesh Agricultural Research Council,Farmgate,Dhaka-1215+2 种基金Bangladesh Agricultural Research Institute(BARI),Joydebpur,Gazipur 1701The work was partially supported by the Taif University Researchers Supporting Project No.(TURSP-2020/39)Taif University,Taif,Saudi Arabia.
文摘Every breeding program that aims to create new and improved cultivars with desired traits mostly relies on information related to genetic diversity.Therefore,molecular characterization of germplasms is important to obtain target cultivars with desirable traits.Sweet potato[Ipomoea batatas(L.)Lam]is widely considered the world’s most important crop,with great diversity in morphological and phenotypic traits.The genetic diversity of 20 sweet potato germplasms originating from Bangladesh,CIP,Philippines,Taiwan,and Malaysia were compared,which was accomplished by genetic diversity analysis by exploring 20 microsatellite DNA markers for germplasm characterization and utilization.This information was effective in differentiating or clustering the sweet potato genotypes.A total of 64 alleles were generated using the 20 primers throughout the 20 germplasm samples,with locus IBS97 having the highest number of alleles(5),whereas locus IbU33 had the fewest alleles(2).The alleles varied in size from 105(IbU31)to 213 base pairs(IBS34).The Polymorphism Information Content(PIC)values for the loci IbL46 and IBS97 varied from 0.445 to 0.730.IBS97 has the highest number of effective alleles(3.704),compared to an average of 2.520.The average Shannon’s diversity index(H)was 1.003,ranging from 0.673 in IbU3 to 1.432 in IBS97.The value of gene flow(Nm)varied between 0.000 and 0.005,with an average of 0.003,whereas genetic differentiation(FST-values)ranged between 0.901 and 1.000.The sweet potato germplasm included in this study had a broad genetic base.SP1 vs.SP9 and SP12 vs.SP18 germplasm pairings had the greatest genetic distance(GD=0.965),while SP1 vs.SP2 germplasm couples had the least genetic diversity(GD=0.093).Twenty genotypes were classified into two groups in the UPGMA dendrogram,with 16 genotypes classified as group“A”and the remaining four genotypes,SP10,SP18,SP19,and SP20,classified as group“B.”According to cluster analysis,the anticipated heterozygosity(gene diversity)of Nei(1973)was 0.591 on average.In summary,SSR markers successfully evaluated the genetic relationships among the sweet potato accessions used and generated a high level of polymorphism.The results of the present study will be useful for the management of germplasm,improvement of the current breeding strategies,and the release of new cultivars as varieties.
