New recessive compound heterozygous variants of RP1L1 in RP1L1 maculopathy

AIM:To identify a maculopathy patient caused by new recessive compound heterozygous variants in RP1L1.METHODS:Comprehensive retinal morphological and functional examinations were evaluated for the patient with RP1L1 maculopathy.Targeted sequence capture array technique was used to screen potential pathologic variants.Polymerase chain reaction and Sanger sequencing were used to confirm the screening results.RESULTS:Fundus examination showed round macular lesions appeared in both eyes.Optical coherence tomography showed that the inner segment/outer segment continuity was disorganized and disruptive in the left eye,but it was uneven and slightly elevated in the right eye.Fundus autofluorescence showed patchy hyper-autofluorescence in the macula.Visual field examination indicates central defects in both eyes.Electroretinogram(ERG)and multifocal ERG showed no obvious abnormalities.Fundus fluorescein angiography in the macula showed obviously irregular hyper-fluorescence in the right eye and slightly hyper-fluorescence in the left eye.We found that the proband carried a missense variant(c.1972C>T)and a deletion variant(c.4717_4718del)of RP1L1,which were originated from the parents and formed compound heterozygous variants.Both variants are likely pathogenic according to the ACMG criteria.Multimodal imaging,ERG and detailed medical history are important diagnostic tools for differentiating between acquired and inherited retinal disorders.CONCLUSION:A maculopathy case with detailed retinal phenotype and new recessive compound heterozygous variants of RP1L1 is identified in a Chinese family,which expands the understanding of phenotype and genotype in RP1L1 maculopathy.

Detection of Novel BEST1 Variations in Autosomal Recessive Bestrophinopathy Using Third-generation Sequencing

Objective:Autosomal recessive bestrophinopathy(ARB),a retinal degenerative disease,is characterized by central visual loss,yellowish multifocal diffuse subretinal deposits,and a dramatic decrease in the light peak on electrooculogram.The potential pathogenic mechanism involves mutations in the BEST1 gene,which encodes Ca2+-activated Cl−channels in the retinal pigment epithelium(RPE),resulting in degeneration of RPE and photoreceptor.In this study,the complete clinical characteristics of two Chinese ARB families were summarized.Methods:Pacific Biosciences(PacBio)single-molecule real-time(SMRT)sequencing was performed on the probands to screen for disease-causing gene mutations,and Sanger sequencing was applied to validate variants in the patients and their family members.Results:Two novel mutations,c.202T>C(chr11:61722628,p.Y68H)and c.867+97G>A,in the BEST1 gene were identified in the two Chinese ARB families.The novel missense mutation BEST1 c.202T>C(p.Y68H)resulted in the substitution of tyrosine with histidine in the N-terminal region of transmembrane domain 2 of bestrophin-1.Another novel variant,BEST1 c.867+97G>A(chr11:61725867),located in intron 7,might be considered a regulatory variant that changes allele-specific binding affinity based on motifs of important transcriptional regulators.Conclusion:Our findings represent the first use of third-generation sequencing(TGS)to identify novel BEST1 mutations in patients with ARB,indicating that TGS can be a more accurate and efficient tool for identifying mutations in specific genes.The novel variants identified further broaden the mutation spectrum of BEST1 in the Chinese population.

Safety and efficacy of transcatheter arterial embolization in autosomal dominant polycystic kidney patients with gross hematuria: Six case reports

BACKGROUND To retrospectively report the safety and efficacy of renal transcatheter arterial embolization for treating autosomal dominant polycystic kidney disease(ADPKD)patients with gross hematuria.CASE SUMMARY The purpose of this study is to retrospectively report the safety and efficacy of renal transcatheter arterial embolization for treating ADPKD patients with gross hematuria.Materials and methods:During the period from January 2018 to December 2019,renal transcatheter arterial embolization was carried out on 6 patients with polycystic kidneys and gross hematuria.Renal arteriography was performed first,and then we determined the location of the hemorrhage and performed embolization under digital subtraction angiography monitoring.Improvements in routine blood test results,routine urine test results,urine color and postoperative reactions were observed and analyzed.Results:Renal transcatheter arterial embolization was successfully conducted in 6 patients.The indices of 5 patients and the color of gross hematuria improved after surgery compared with before surgery.No severe complication reactions occurred.CONCLUSION For autosomal dominant polycystic kidney syndrome patients with gross hematuria,transcatheter arterial embolization was safe and effective.

Incidental renal cell carcinoma post bilateral nephrectomy in autosomal dominant polycystic kidney disease

BACKGROUND Renal cell carcinoma(RCC)is more common in patients with autosomal dominant polycystic kidney disease(ADPKD)than in the general population.Diagnosing RCC in ADPKD is challenging due to the presence of multiple renal cysts,often leading to delays and difficulties in distinguishing RCC from cyst infection or hemorrhage.A total of 38 kidneys were excised from 19 patients,with a mean age of 56.8 years and an average hemodialysis duration of 84.2 months.Eight patients underwent open nephrectomies,and 11 underwent hand-assisted laparoscopic nephrec-tomies.RCC was detected in 15.8%of kidneys,affecting 21.1%of patients.Two patients had multifocal RCC in both kidneys.All RCC cases were pT1 stage,with the largest lesion averaging 16.5 mm in diameter.The average operative duration was 120 minutes,with intraoperative blood loss averaging 184.2 mL.Five patients required blood transfusions.Postoperative complications occurred in five patients,with a mean hospital stay of 17.1 days.The mean follow-up period was 28.1 months.CONCLUSION The prevalence of RCC is higher in patients with ADPKD with ESRD than in those with ESRD alone.Thus,clinicians should be cautious and implement surveillance programs to monitor the development of RCC in patients with ADPKD,particularly those on dialysis.

SCR-22 of pollen-dominant S haplotype class is recessive to SCR-44 of pollenrecessive S haplotype class in Brassica rapa

SCR/SP11 encodes the male determinant of recognition specificity of self-incompatibility(SI)in Brassica species and is sporophytically expressed in the anther tapetum.Based on dominance relationships in pollen and nucleotide sequence similarity,the S haplotypes in Brassica have been classified as class I or class II,with class-I S haplotypes being dominant over class-II S haplotypes.Here,we revealed that S-22 in B.rapa belonging to class I is recessive to class-II S-44 and class-I S-36 in pollen,whereas it is dominant over S-60,S-40,and S-29 based on pollination tests.SCR/SP11 of S-22(SCR-22)was sequenced,revealing that the deduced amino-acid sequence of SCR-22 has the longest C-terminal domain among the SCR/SP11 sequences.The expression of SCR-22 was found to be suppressed in S-22/S-44 and S-22/S-36 heterozygotes.Normal transcription of SCR-44 was considered to be due to the transcription suppression of Smi sRNA of the S-22 haplotype and a very low methylation state of the SCR-44 promoter region in the tapetum of S-22/S-44 heterozygotes.In SCR-22,only the cytosine residue located at the–37 bp position of the promoter region was hypermethylated in the tapetum of S-22/S-44 heterozygotes,and few methylated cytosines were detected in the promoter and coding regions of SCR-22 in S-22/S-36 heterozygotes.SCR-22 was also expressed in microspores in S-22 homozygotes but not in S-22/S-44 and S-22/S-36 heterozygotes.These results suggest that a mechanism different from class-II SCR/SP11 suppression may operate for the suppression of recessive class-I SCR-22 in S heterozygotes.

Distribution and dynamics of niche and interspecific association of dominant phytoplankton species in the Feiyun River basin,Zhejiang,China

To investigate the dominant species and interspecific association in the phytoplankton community of the Feiyun River basin in Zhejiang Province,East China,the main stream and the Shanxi Zhaoshandu Reservoir in the downstream were chosen as the study area,for which 22 sampling sites were designated.Sampling was conducted in September 2021,January,May,and July 2022.Phytoplankton species were identified from both quantitative samples and in-vivo observations.Phytoplankton was quantified by direct counting.Results show that there were 98 species belonging to 6 phyla and 78 genera.In addition,to clarify the niches of the dominant phytoplankton species and their interspecific association,the dominance index was calculated,and a comprehensive analysis was conducted including niche width,niche overlap value,ecological response rate,overall association,chi-square test,and the stability.The phytoplankton community exhibited characteristics of a Cyanobacteria-Chlorophyta-Diatom type community,showing higher diversity in spring and lower diversity in summer.Among 11 dominants phytoplankton species from 3 phyla,both frequency and dominance degree varied seasonally,of which Microcystis sp.was the dominant species in Spring,Autumn,and Winter.The niche widths of the dominant species ranged from 0.234 to 0.933,and were categorized into three groups.The niche overlap values of the 11 dominant species ranged from 0.359 to 0.959,exhibiting significant seasonal differences-highest in winter followed by autumn,spring,and summer in turn.The overall correlation among dominant species in all four seasons revealed a non-significant negative association,resulting in an unstable community structure.A significant portion(84.2%)of species pairs displayed positive associations,suggesting a successional pattern where Diatoms dominated while other dominant species shared resources and space.Despite this pattern,stability measurements indicated that the dominant species community remained unstable.Therefore,careful monitoring is recommended for potential water environment issues arising from abnormal proliferation of dominant species in the watershed during winter.This research built a theoretical foundation with a data support to the early warning of eutrophication and provided a reference for water resources management in similar watersheds along the eastern coast of China.

Species’ geographical range, environmental range and traits lead to specimen collection preference of dominant plant species of grasslands in Northern China

Many different factors,such as species traits,socio-economic factors,geographical and environmental factors,can lead to specimen collection preference.This study aims to determine whether grassland specimen collection in China is preferred by species traits(i.e.,plant height,flowering and fruiting period),environmental range(i.e.,the temperature and precipitation range)and geographical range(i.e.,distribution range and altitudinal range).Ordinary least squares models and phylogenetic generalized linear mixed models were used to analyze the relationships between specimen number and the explanatory variables.Random Forest models were then used to find the most parsimonious multivariate model.The results showed that interannual variation in specimen number between 1900 and 2020 was considerable.Specimen number of these species in southeast China was notably lower than that in northwest China.Environmental range and geographical range of species had significant positive correlations with specimen number.In addition,there were relatively weak but significant associations between specimen number and species trait(i.e.,plant height and flowering and fruiting period).Random Forest models indicated that distribution range was the most important variable,followed by flowering and fruiting period,and altitudinal range.These findings suggest that future floristic surveys should pay more attention to species with small geographical range,narrow environmental range,short plant height,and short flowering and fruiting period.The correction of specimen collection preference will also make the results of species distribution model,species evolution and other works based on specimen data more accurate.

Complex adaptive system theory,agent-based modeling,and simulation in dominant technology formation

Dominant technology formation is the key for the hightech industry to“cross the chasm”and gain an established foothold in the market(and hence disrupt the regime).Therefore,a stimulus-response model is proposed to investigate the dominant technology by exploring its formation process and mechanism.Specifically,based on complex adaptive system theory and the basic stimulus-response model,we use a combination of agent-based modeling and system dynamics modeling to capture the interactions between dominant technology and the socio-technical landscape.The results indicate the following:(i)The dynamic interaction is“stimulus-reaction-selection”,which promotes the dominant technology’s formation.(ii)The dominant technology’s formation can be described as a dynamic process in which the adaptation intensity of technology standards increases continuously until it becomes the leading technology under the dual action of internal and external mechanisms.(iii)The dominant technology’s formation in the high-tech industry is influenced by learning ability,the number of adopting users and adaptability.Therein,a“critical scale”of learning ability exists to promote the formation of leading technology:a large number of adopting users can promote the dominant technology’s formation by influencing the adaptive response of technology standards to the socio-technical landscape and the choice of technology standards by the socio-technical landscape.There is a minimum threshold and a maximum threshold for the role of adaptability in the dominant technology’s formation.(iv)The socio-technical landscape can promote the leading technology’s shaping in the high-tech industry,and different elements have different effects.This study promotes research on the formation mechanism of dominant technology in the high-tech industry,presents new perspectives and methods for researchers,and provides essential enlightenment for managers to formulate technology strategies.

Square Logistic Model for the Appearance of Lethal Recessive Homozygous Genotype in Random Mating Population

From the random mating population of maize, the relationship between heterosis and albino seedling was analyzed by means of mathematical theory, further the square logistic model for the appearance of lethal recessive homozygous genotype was deduced. The model shows that heterosis can determine the genetic structure and proportion of population. It approves, that the proportion of aa in each generation of maize seedlings shows a similar Logistic curve in growth process till equilibrium, so long as Aa containins lethal gene a from mutation presents heterosis. The ratio of equilibrium state of aa is determined by the ratio of AA-Aa fitness. Heterosis is helpful for the keeping of genetic diversity of population.

Criteria Condition for Generalized Diagonally Dominant Matrices

In this paper, we provide some new necessary and sufficient conditions for generalized diagonally dominant matrices and also obtain some criteria for nongeneralized dominant matrices.

Criteria Conditions for Generalized Diagonally Dominant Matrices

In this paper, some new sufficient conditions for generalized dominant matrices are given, and some results in [1] are generalized and improved.

Tesevatinib ameliorates progression of polycystic kidney disease in rodent models of autosomal recessive polycystic kidney disease

AIMTo investigate the therapeutic potential of tesevatinib （TSV）, a unique multi-kinase inhibitor currently in Phase Ⅱ clinical trials for autosomal dominant polycystic kidney disease （ADPKD）, in well-defined rodent models of autosomal recessive polycystic kidney disease （ARPKD）. METHODSWe administered TSV in daily doses of 7.5 and 15 mg/kg per day by I.P. to the well characterized bpk model of polycystic kidney disease starting at postnatal day（PN） 4 through PN21 to assess efficacy and toxicity in neonatal mice during postnatal development and still undergoing renal maturation. We administered TSV by oral gavage in the same doses to the orthologous PCK model （from PN30 to PN90） to assess effcacy and toxicity in animals where developmental processes are complete. The following parameters were assessed： Body weight, total kidney weight; kidney weight to body weight ratios; and morphometric determination of a cystic index and a measure of hepatic disease. Renal function was assessed by： Serum BUN; creatinine; and a 12 h urinary concentrating ability. Validation of reported targets including the level of angiogenesis and inhibition of angiogenesis （active VEGFR2/KDR） was assessed by Western analysis.RESULTSThis study demonstrates that： （1） in vivo pharmacological inhibition of multiple kinase cascades with TSV reduced phosphorylation of key mediators of cystogenesis： EGFR, ErbB2, c-Src and KDR; and （2） this reduction of kinase activity resulted in signifcant reduction of renal and biliary disease in both bpk and PCK models of ARPKD. The amelioration of disease by TSV was not associated with any apparent toxicity.CONCLUSIONThe data supports the hypothesis that this multi-kinase inhibitor TSV may provide an effective clinical therapy for human ARPKD.

Drug Sensitive Test on Main Pathogenic Bacteria of Cow Recessiveness Mastitis Using Traditional Chinese Medicine Preparation “Zengrujianniusan”

According to the theory of Chinese veterinary medicine and characteristics of Chinese herbal medicine, four different preparations of compound Chinese medicine ＂Zengrujianniusan＂ were composed, and the prepared water decoction was used to carry on the bacteriostatic test on main pathogens of cow recessiveness mastitis. The results showed that the four different prescriptions of water decoction all had antibacterial effects. The prescription 3 was sensitive to Staphylococcus aureus and Streptococcus agalactiae, while the other three prescriptions showed high sensitivity, and the prescription 3 had the strongest bacteriostatic effects.

Criteria Conditions for Generalized Diagonally Dominant Matrices

In this paper, we provide some new criteria conditions for generalized strictly diagonally dominant matrices, such that the corresponding results in [1] are generalized and improved.

Genetic Analysis and Mapping of Genes Involved in Fertility of Pingxiang Dominant Genic Male Sterile Rice

Pingxiang-dominant genic male sterile rice （PDGMSR） was the first dominant genic male sterile mutant identified in rice （Oryza sativa L.）, and the corresponding dominant genic male sterile gene was designated as Ms-p. The fertility of PDGMSR can be restored by introduction of a dominant epistatic fertility restoring gene in some rice varieties. In the present study, E823, an indica inbred rice variety, restored the fertility of PDGMSR, and the genetic pattern was found to be consistent with a dominant epistatic model, therefore, the dominant epistatic fertility restorer gene was designated as Rfe. The F2 population from the cross of PDGMSR/E823 was developed to map gene Rfe. The F2 plants with the genotypes Ms-pMs-pRferfe or Ms-pms-pRferfe were used to construct a fertile pool, and the corresponding sterile plants with genotypes Ms-pMs-prferfe or Ms-pms-prferfe were used to con- struct a sterile pool. The fertility restoring gene Rfe was mapped to one side of the microsatellite markers RM311 and RM3152 on rice chromosome 10, with genetic distances of 7.9 cM and 3.6 cM, respectively. The microsatellite markers around the location of the Ms-p gene were used to finely map the Ms-p gene. The findings of this study indicated that the microsatellite markers RM171 and RM6745 flanked the Ms-p gene, and the distances were 0.3 cM and 3.0 cM, respectively. On the basis of the sequence of rice chromosome 10, the physical distance between the two markers is approximately 730 kb. These findings facilitates molecular marker-assisted selection （MAS） of genes Ms-p and Rfe in rice breeding programs, and cloning them in the future.

Variation of SPAD values in uneven-aged leaves of different dominant species in Castanopsis carlessi forest in Lingshishan National Forest Park

The greenness （SPAD） of uneven-aged leaves of dominant species in the Castanopsis carlessi forest at different altitude gradients in Lingshishan National Forest Park, Fujian Province, China were measured by using portable chlorophyll meter SPAD-502. In addition, the correlation between SPAD value and the concentration of chlorophyll and foliar nitrogen was also investigated. Significant variations in SPAD values were found between the uneven-aged leaves of different dominant species and different altitude gradients. Regression analysis showed that SPAD value was significantly correlated with the concentration of chlorophyll and the content of foliar nitrogen, indicating that SPAD value could be indicators for foliar chlorophyll and nitrogen. It is suggested that SPAD meter is a useful tool for forest assessments in decision-making and operational nutrient management programs.

Study on the Water Balance in Three Dominant Plants with Simulated Precipitation Change in Maowusu Sandland

The distribution pattern and productivity of Maowusu sandland terrestrial ecosystem are greatly affected with the future severe global change, especially global precipitation change. Considering the predicative global precipitation change and the appropriate relevant strategy for the sustainable development of the China dry territory, the authors have investigated the response of water balance to global precipitation change by creating an artificial control of four levels of water supply treating 3 dominant plants in Mauwusu sandland. The results showed that the seasonal changes of water storage and moisture of different sandland layer depths were affected by different water supply treatments and different plants. The water storage of the three plant growing sandlands and the moisture of different sandland layer depths increased as water supply was increased. The moisture of different water supply treatments and plants increased with the increase of sandland layer depth. The water storage and moisture of the same layer depth of Hedysarum mongolicum Turcz. growing sandland were larger than that of Salix psammophila C. Wang et Ch. Y. Yang growing sandland, which were in turn higher than that of Artemisia ordosica Krasch. growing sandland in the same water supply treatment. Water supply significantly affected the seasonal changes of evaporation and transpiration of the three plant growing sandlands. With the increased levels of water supply, viz. 157.5 mm, 315.0 mm, 472.5 mm and 630.0 mm, the total evaporation was 123.66 mm, 258.68 mm, 376.30 mm, 458.57 mm, respectively, and the total transpiration of A. ordosica was 50.80 mm, 68.93 mm, 108.39 mm, 163.36 mm, respectively, and that of S. psammophila , 47.37 mm, 68.17 mm, 93.65 mm, 135.97 mm, respectively, and that of H. mongolicum 46.73 mm, 67.37 mm, 86.07 mm, 109.64 mm, respectively. Evaporation was significantly higher than transpiration in the experiment.

What determines the number of dominant species in forests?

In this work, the difference in number of dominant species in a community on global scale and successional trajectories was analyzed based on the published data. We explained the reasons of these differ-ences using a resource availability hypothesis, proposed in this work, that the distribution of available resource determined the pattern of commu-nity dominance. The results showed that on global scale the number of dominant species of community varied across latitudinal forest zone, namely from single-species dominance in boreal and temperate forest to multi-species codominance, even no dominant species in tropical forest. This was consistent with the pattern of resource distribution on global scale. Similarly, in successional trajectories, the number of dominant species gradually radiated from single-species dominance to multi-species codominance, even no dominant species in tropical forest. The changing available resources in trajectories were responsible for this difference. By contrary, a community was often dominated by single species in temperate or boreal forest. This was determined by the low available resource, especially low available water and temperature. In boreal forest, low temperature greatly reduced availability of water and nutrient, which were responsible for the single-species dominance. In addition, the conclusion that high available resources sustained low dominance of community might be deduced, based on the fact that the dominance of community declined with the increasing of species diversity. To sum up, the richer the available resources were, the lower the dominance of community was, and vice versa. The hypothesis that the resource availability controlled the dominance of community could well elucidate the difference of community dominance on global and community scale.

A COMPLETE SCREEN FOR MUTATIONS OF THE RHODOPSIN GENE IN A PANEL OF CHINESE PATIENTS WITH AUTOSOMAL DOMINANT RETINITIS PIGMENTOSA

Objective To evaluate the prevalence of rhodopsin (RHO) mutations and the genotype-phenotype relationships in Chinese patients with autosomal dominant retinitis pigmentosa (ADRP) by conformation sensitive gel electrophoresis (CSGE) and direct DNA sequencing. Methods We have screened the five coding exons and splice sites of RHO gene in 27 probands who had no relativity from Chinese ADRP families and 100 normal controls to identify disease-associated mutations, using CSGE and direct DNA sequencing. Family members of some probands with disease-associated mutations were also genotyped to determine whether the RHO mutations segregated with retinitis pigmentosa (RP) in their families. Results Two RHO mutations, Pro347Leu and Pro327 (1-bp del), were identified separately in two families, thus the frequency of RHO mutations among this set of Chinese ADRP families is about 7.4% (2/27). Pro347Leu mutation was found in one ADRP proband as well as three her children who also had RP. She had relatively early onset at about 17 years. The only one child without this mutation had no symptom or sign of RP at age of 34. Pro327 (1-bp del) was identified in a late-onset ADRP patient, who appeared night blindness around 30 years old and in her fifties electroretinogram (ERG) has been flat in both scotopic and photopic phases. Family analysis showed that this mutation also existed in her younger dau-ghter and her elder sister, both of them also had RP. Three other family members were genotypically and phenotypically normal. Neither of the two mutations was detected in 100 normal controls.Conclusions The frequency of RHO mutations in Chinese patients was lower than that in Europe and North America. The phenotype of the patients with Pro347Leu corresponded to type 1 ADRP, with severe rod degeneration and some cone preservation later, while the phenotype of the patients carrying Pro327 (1-bp del) corresponded to type 2 ADRP, with a concomitant loss of rod and cone visual function. CSGE was found to be a sensitive, simple, and practical method for the screening of a large number of samples under highly reproducible conditions, and could be utilized in routine molecular diagnostic laboratories.

A novel frameshift mutation in CX46 associated with hereditary dominant cataracts in a Chinese family

AIM：To investigate the genetic mutations that are associated the hereditary autosomal dominant cataract in a Chinese family.METHODS：A Chinese family consisting of 20 cataract patients（including 9 male and 11 female） and 2 unaffected individuals from 5 generations were diagnosed to be a typical autosomal dominant cataract pedigree. Genomic DNA samples were extracted from the peripheral blood cells of the participants in this pedigree. Exon sequence was used for genetic mutation screening. In silico analysis was used to study the structure characteristics of connexin 46（CX46） mutant. Immunoblotting was conduceted for testing the expression of CX46.RESULTS：To determine the involved genetic mutations, 11 well-known cataract-associated genes（cryaa, cryab, crybb1, crybb2, crygc, crygd, Gja3, Gja8, Hsf4, Mip and Pitx3） were chosen for genetic mutation test by using exon sequencing. A novel cytosine insertion at position 1195 of CX46 c DNA（c.1194_1195ins C） was found in the samples of 5 tested cataract patients but not in the unaffected 2 individuals nor in normal controls, which resulted in 30 amino acids more extension in CX46Cterminus（cx46fs400） compared with the wild-type CX46. In silico protein structure analysis indicated that the mutant showed distinctive hydrophobicity and protein secondary structure compared with the wild-type CX46. The immunoblot results revealed that CX46 protein, which expressed in the aging cataract lens tissues, was absence in the proband lens. In contrast, CX50, alpha A-crystallin and alphaB-crystallin expressed equally in both proband and aging cataract tissues. Those results revealed that the cx46fs400 mutation could impair CX46 protein expression. CONCLUSION：The insertion of cytosine at position 1195 of CX46 cD NA is a novel mutation site that is associated with the autosomal dominant cataracts in this Chinese family. The C-terminal frameshift mutation is involved in regulating CX46 protein expression.