Changes in macrophage infiltration and podocyte injury in lupus nephritis patients with repeated renal biopsy: Report of three cases

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.

Axial length shortening in myopic children with Stickler syndrome after repeated low-level red-light therapy

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.

Comparative analyses of mitogenomes in the social bees with insights into evolution of long inverted repeats in the Meliponini

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.

Repeatability,interocular correlation and agreement of optic nerve head vessel density in healthy eyes:a sweptsource optical coherence tomographic angiography study

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.

Toward understanding the role of genomic repeat elements in neurodegenerative diseases

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.

GATA binding protein 2 mediated ankyrin repeat domain containing 26 high expression in myeloid-derived cell lines

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.

DNA Tandem Repeats as Iterable Objects to Count Cell Divisions: A Computational Model

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.

Effects of repeated applications of fungicide carbendazim on its persistence and microbial community in soil

Carbendazim, a systemic benzimidazole fungicide, is applied repeatedly to control plant diseases including soilborne diseases, over a growing season. Studies were carried out under laboratory conditions to assess the effects of repeated carbendazim applications on its persistence and microbial community in soil. The results indicate that dissipation of carbendazim in soil was accelerated with its application frequency. The degradation rate constant of carbendazim was increased significantly from 0.074 d-1 to 0.79 d-1. The corresponding half-life was shorten markedly from 9.3 d to 0.9 d after four repeated applications. No significant inhibitory effect of carbendazim on soil microbial utilization of the carbon sources was observed after first treatment, but a slight increase in average well color development （AWCD） was shown after second, third, and fourth applications. It suggested that soil microorganisms become adapted to carbendazim after repeated application. Simpson and Shannon indexes of soil microbial community from carbendazim treated soil were also similar to those from the control soil, indicating that the richness and dominant character of soil microorganisms remain unchangeable after repeated application. However, after first, second, and third addition of carbendazim, McIntosh indexes on day 21 were significantly higher compared with the control, suggesting that balance of soil microorganisms was altered due to the enrichment of the specific carbendazim-adapting strains in soil

Human-induced landslide on a high cut slope: a case of repeated failures due to multi-excavation

The paper attempts to represent a case of repeated failures on a high cut slope due to multi-excavation. The characteristics of each failure induced by excavation are analyzed through geological investigation, and then a geological model at different failure stages is proposed. The geological analysis shows that the excavation-induced repeated failures are related to the exposure of the weak bedding plane and the toe unloading of the cut slope, Numerical modeling is conducted based on a sequential method, taking into account the main failure stages of cut slope. The simulation results fairly coincide with the practical phenomena observed in field. It is shown that the decrease in normal stress of displaced mass on cut slope will induce the increase in shear stress in bedding planes and that at the toe of the cut slope. The released stress leads to repeated gravitational instabilities of cut slope due to the decrease in normal stress and the increase in shear stress along the bedding planes of mudstone.

Repeated lumps and infections: A case report on breast augmentation complications

BACKGROUND Polyacrylamide hydrogel(PAAG)injections were once common in breast augmentation and have been prohibited for augmentation mammaplasty in China since a large number of patients who underwent breast augmentation with PAAG injections have continued to seek medical advice as a result of related complications.Among all these complications,distant migration is relatively rare.CASE SUMMARY A 49-year-old female presented at the hospital with a one-year history of a vulvar lump.The sonography of the lump showed several subcutaneous fluid-filled regions from the left vulva to the pubic symphysis,which suggested possible fat liquefaction.An enhanced magnetic resonance imaging(MRI)revealed a cystic area,which was considered a benign lesion.Intraoperative observations showed that the mass did not have an obvious capsule,the subcutaneous tissue presented as a cavity,and some yellow material came out of this cavity.A culture of the drainage did not show bacterial contamination.Histopathology revealed a foreign body granuloma.After resection and closed drainage,lumps were successively observed in the left lower abdomen and the bilateral hypochondriac region with infections.Sonography found that the hypoechoic areas in the bilateral hypochondriac region seemed continuous with deep in the breasts.The patient reported that she had undergone surgery with PAAG injections 20 years ago after she was repeatedly asked about her past history.Finally,a diagnosis of distant migration of PAAG was made.CONCLUSION PAAG gel can migrate after long periods of time.A diagnosis should not be limited to the area where the symptom develops.

Repeated vitrification/warming of human sperm gives better results than repeated slow programmable freezing

In this study, we compared the effects of repeated freezing/thawing of human sperm by our in-house method of rapid freezing with slow programmable freezing. Sperm samples from 11 normozoospermic subjects were processed through density gradients and divided into three aliquots： non-frozen, rapid freezing and slow programmable freezing. Sperm in the rapid freezing group had better motility and viability than those in the slow freezing group （P〈O.01） after the first, second and third cycles of freezing/thawing, but there was no difference in morphology. In the second experiment, rapid freezing was repeated three times in 20 subjects. The samples from each thawing cycle were evaluated for DNA fragmentation using the alkaline comet assay. DNA fragmentation began to increase considerably after the second cycle of freezing/thawing, but to a level that was not clinically important. In the third experiment, rapid freezing was done repeatedly in 10 subjects, until no motile sperm were observed after thawing. The median number of repeated freezing/thawing that yielded no motile sperm was seven （range： 5-8, mean： 6.8）. In conclusion, we demonstrated that repeated freezing/thawing of processed semen using our rapid freezing method gave better results than standard slow programmable freezing. This method can help maximize the usage of precious cryopreserved sperm samples in assisted reproduction technology.

Subchronic Oral Toxicity Evaluation of Lanthanum： A 90-day, Repeated Dose Study in Rats

Objective The present study was undertaken to evaluate the subchronic toxicity of lanthanum and to determine the no observed adverse effect level（NOAEL）,which is a critical factor in the establishment of an acceptable dietary intake（ADI）.Methods In accordance with the Organization for Economic Co-operation and Development（OECD） testing guidelines,lanthanum nitrate was administered once daily by gavage to Sprague-Dawley（SD） rats at dose levels of 0,1.5,6.0,24.0,and 144.0 mg/kg body weight（BW） per day for 90 days,followed by a recovery period of 4 weeks in the 144.0 mg/kg BW per day and normal control groups.Outcome parameters were mortality,clinical symptoms,body and organ weights,serum chemistry,and food consumption,as well as ophthalmic,urinary,hematologic,and histopathologic indicators.The benchmark dose（BMD） approach was applied to estimate a point of departure for the hazard risk assessment of lanthanum.Results Significant decreases were found in the 144.0 mg/kg BW group in the growth index,including body weight,organ weights,and food consumption.This study suggests that the NOAEL of lanthanum nitrate is 24.0 mg/kg BW per day.Importantly,the 95% lower confidence value of the benchmark dose（BMDL） was estimated as 9.4 mg/kg BW per day in females and 19.3 mg/kg BW per day in males.Conclusion The present subchronic oral exposure toxicity study may provide scientific data for the risk assessment of lanthanum and other rare earth elements（REEs）.

Purposeless repeated acquisition time-lapse seismic data processing

In China, most oil fields are continental sedimentation with strong heterogeneity, which on one side makes the reservoir prospecting and development more difficult, but on the other side provides more space for searching residual oil in matured fields. Time-lapse seismic reservoir monitoring technique is one of most important techniques to define residual oil distribution. According to the demand for and development of time-lapse seismic reservoir monitoring in China, purposeless repeated acquisition time-lapse seismic data processing was studied. The four key steps in purposeless repeated acquisition time-lapse seismic data processing, including amplitude-preserved processing with relative consistency, rebinning, match filtering and difference calculation, were analyzed by combining theory and real seismic data processing. Meanwhile, quality control during real time-lapse seismic processing was emphasized.

The Construction of Active Source Repeated Monitoring in the Qilian Mountain, Gansu Province

The exciting source of the active source repeated monitoring is located in the Xiliushui Reservoir in Zhangye,Gansu Province. The system began operating normally on July 9,2015,and we had completed a period of 40 days of continuous excitation experiment before November 10,2015. Our results reveal that the airgun source has good consistency and repeatability,and the detective system of active source can record signal clearly. The construction of active source repeated exploration projects has achieved some results,which can provide valuable experience for the research of active source repeated exploration. The observation data we obtained makes it possible to follow the temporal and spatial variations of the deep structure of the Qilian Mountain areas.

Pituitary Suppression before Frozen Embryo Transfer Is Beneficial for Patients Suffering from Idiopathic Repeated Implantation Failure

Long-term gonadotropin-releasing hormone agonist（Gn RHa） administration before in vitro fertilization（IVF）/intracytoplasmic sperm injection（ICSI） in infertile women with endometriosis or adenomyosis significantly enhanced the chances of pregnancy in both fresh and frozen embryo transfer cycles. We hypothesized that long-term Gn RHa treatment might also be beneficial for the idiopathic repeated implantation failure（RIF） patients. In the 21 patients receiving Gn RHa and hormone replacement therapy（G-HRT） protocols for frozen embryo transfer, their data were compared with those of the 56 of frozen/fresh cycles they had previously undergone（previous protocols）. Comparison showed that the finial results were significantly better with G-HRT protocols than with their previous protocols, with pregnancy rate, clinical pregnancy rate, implantation rate and on-going pregnancy rate being 70%, 60%, 40% and 38% respectively with G-HRT protocols, against 17%, 11%, 6.3% and 5% with previous protocols. The results showed that hormonally controlled endometrial preparation with prior Gn RHa suppression could be used for patients who had experienced repeated failures of IVF treatment despite having morphologically optimal embryos, and the treatment may help increase the receptivity of the endometrium in these patients.

Strength and Chloride Diffusion Behaviour of Three Generations of Repeated Recycled Fine Aggregate Concrete

The feasibility of using different generations of recycled fine aggregate（RFA） in structural concrete in a chloride environment was evaluated by studying the performance of the RFA and the corresponding concrete. The different generations of RFA were recycled by following the cycle of ‘concrete-waste concrete-fine aggregate-concrete＇. The properties of three generations of repeatedly recycled fine aggregate（RRFA） were systematically investigated, and we focused on the compressive strength and splitting tensile strength and chloride ion permeability of the related structural concretes with 25%, 75%, and 100% replacement of natural fine aggregates with RFA. The results indicated that the quality of RRFA presents a trend of slow deterioration, but the overall performance of all RRFA still fulfils the quality requirements of recycled fine aggregate for structural concrete. All RRFA concretes achieved the target compressive strength of 40 MPa after 28 days except for the second generation of the recycled aggregate concrete and the third generation of the recycled aggregate concrete with 100% replacement, and all the concrete mixes achieved the target compressive strength after 90 days. The insights obtained in this study demonstrate the feasibility of using at least three generations of RRFA for the production of normal structural concrete with a design service life of 100 years in a chloride environment.

A FAMILY OF MODAL METHODS FOR COMPUTING EIGENVECTOR DERIVATIVES WITH REPEATED ROOTS

A family of modal methods for computing eigenvector derivatives with repeated roots are directly derived from the constraint generalized inverse technique which is originally formulated by Wang and Hu. Extensions are made to Akgun's method to allow treatment of eigensensitivity with repeated roots for general nondefective systems, and Bernard and Bronowicki's modal expansion approach is expanded to a family of modal methods.

Monitoring on subsidence due to repeated excavation with DInSAR technology

DInSAR technology was used to monitor subsidence caused by underground coal mining activities in mountainous area, with multi source SAR data, including 8 EnviSAT C-band and 4 ALOS L-band, and 4 programmed TerraSAR-X dataset. The results revealed that 2-pass DInSAR technique sometimes failed to retrieve the mining-caused subsidence due to spatial and/or temporal de-correlation. We also noticed that there existed residual topographic phase after the compensation with SRTM DEM, which could almost overwhelm the subsidence information when the perpendicular baseline was relatively large. Based on the mining materials, analysis was made on the shape of subsidence area. For the well geocoded results from TerraSAR-X, confirmed by GPS surveying results of corner reflectors, we tried to extract the advance distance of influence besides the subsidence area. Due to the big deformation gradient over stopingfaces, the X-band SAR data could not capture the maximum value subsidence revealed by GPS survey in our preliminary results, the same as C-band EnviSAT data. This will turn to be our research subject in the next few months.

A Mechanical Model for Three-phase Permanent Deformation of Asphalt Mixture under Repeated Load

On basis of the Burgers model, a new model consisting of modified dashpot and Van Der Poel model was derived from rheological and viscoelastic theory. Subsequently, triaxial repeated load permanent deformation tests of AC16 asphalt mixtures were conducted to validate this new developed model. Parameters of new developed model were obtained by a nonlinear regression analysis of test data, and then permanent strains and flow number of each mixture were calculated. The experimental results prove that the new developed model can well describe three phases permanent deformation of asphalt mixture under repeated load and it can be used for pavement mechanical analysis and rutting prediction.

Photosynthesis of Digitaria ciliaris during repeated soil drought and rewatering

The ability of psammophyte photosynthesis to withstand and recover from severe droughts is crucial for vegetation sta- bility in semi-arid sandy lands. The responses of gas exchange and chlorophyll fluorescence of an annual grass, Digitaria ciliaris, were measured through three soil drought and rewatering cycles. Results showed that the net photosynthesis rate （P,） decreased by 92%, 95%, and 63% at end of the three drought periods, respectively, water use efficiency （WUE） decreased by 67%, 54%, and 48%, while the constant intercellular CO2 concentration （Ci） increased by 1.08, 0.88, and 0.45 times. During those three cycles, the trapping probability with no dark adaptation （Fv＇/Fm＇） decreased by 55%, 51%, and 9%, the electron transport per cross section （ET0＇/CS0＇） decreased by 63%0, 42%, and 18%, and the dissipation per cross section （DI0＇/CS0＇） increased by 97%, 96%, and 21%. These results indicated that D. ciliaris was subjected to photoinhi- bition and some non-stomatal limitation of photosynthesis under drought. However, after four days of rewatering, its photosynthetic characteristics were restored to control values. This capability to recover from drought may contribute to making the plant＇s use of water as efficient as possible. Furthermore, the photosynthesis decreased more slowly in the subsequent drought cycles than in the first cycle, allowing D. ciliaris to enhance its future drought tolerance after drought hardening. Thus, it acclimatizes itself to repeated soil drought.