Background:The absence of well-established immunosuppressed rabbit models poses a significant hurdle in xenograft experiments.Tacrolimus has been identified as a highly promising immunosuppressive agent for rabbits.Ho...Background:The absence of well-established immunosuppressed rabbit models poses a significant hurdle in xenograft experiments.Tacrolimus has been identified as a highly promising immunosuppressive agent for rabbits.However,determining the optimal dosage and route of administration to minimize toxicity while maintaining efficacy remains challenging.Methods:In this study,we investigated the effect of orally administered tacrolimus in rabbits,with an aim to achieve a whole blood target trough level of 3-10 ng/m L,and looked at signs of tissue rejection after the transplantation of a human nerve conduit to repair a severed fibular nerve.An oral dosage range of 0.25-1.5 mg/kg/d was studied for up to 1 year in 63 New Zealand rabbits.Results:We demonstrated the feasibility of long-term grafting in rabbits while maintaining safe immunosuppression,with side effects mainly limited to diarrhea.Customizing the administered dose proved crucial for graft efficacy and low toxicity,which translated into 100%individual survival.We suggest an oral tacrolimus dose of 1.0-1.5 mg/kg depending on individual heterogeneity and recommend to implement a close therapeutic drug monitoring in the rabbits to maintain a whole blood tacrolimus trough level within the range of 5-12 ng/m L,as levels below 5 ng/m L showed signs of inflammation in the graft.Conclusion:The oral administration of tacrolimus enabled efficient immunosuppression of rabbits over a 1-year period without significant side effects or loss of animals.展开更多
Chronic pancreatitis(CP)is a progressive and irreversible fibroinflammatory disease that markedly increases susceptibility to pancreatic cancer and remains without effective targeted therapies.Among the genetic contri...Chronic pancreatitis(CP)is a progressive and irreversible fibroinflammatory disease that markedly increases susceptibility to pancreatic cancer and remains without effective targeted therapies.Among the genetic contributors to CP,the carboxypeptidase A1 p.Ser282Pro(CPA1^(S282P))variant has been proposed to promote disease through misfolding-induced endoplasmic reticulum stress(ERS),although the broader pathogenic landscape remains incompletely defined.This study generated a rabbit model mimicking the human CPA1S282P mutation using the SpRY-ABE-8.17 system.Homozygous CPA1^(S282P)rabbits exhibited characteristic human CP phenotypes following alcohol induction,including visceral pain,elevated serum lipase and amylase,inflammatory cell infiltration,and extensive pancreatic fibrosis.Biochemical analyses confirmed that the p.S282P mutation induced CPA1 misfolding and elevated the expression of ERS markers GRP78 and CHOP in both transfected HEK293T cells and homozygous mutant rabbits.Notably,the CPA1^(S282P)mutation markedly disrupted intra-pancreatic lipid homeostasis,contributing to the development of CP in mutant rabbits.This study successfully established the first rabbit model of CP that accurately recapitulates CP caused by a defined human point mutation.Additionally,this study provides insights into a previously unrecognized link between CPA1 and intra-pancreatic lipid metabolism,offering a foundation for identifying novel therapeutic targets for human CP.展开更多
Glaucoma,a visual thief,is characterized by elevated intraocular pressure(IOP)and the loss of retinal ganglion cells(RGCs).Selecting suitable animals for preclinical models is of great significance in research on the ...Glaucoma,a visual thief,is characterized by elevated intraocular pressure(IOP)and the loss of retinal ganglion cells(RGCs).Selecting suitable animals for preclinical models is of great significance in research on the prevention,early screening,and effective treatments of glaucoma.Rabbit eyeballs possess similar vascularity and aqueous humor outflow pathways to those of humans.Thus,they are among the earliest in vivo models used in glaucoma research.Over the years,rabbit models have made substantial contributions to understanding glaucomatous pathophysiology,surgical adaptations,biomedical device development,and drug development for reducing IOP,protecting RGCs,and inhibiting fibrosis.Compared to other animals,rabbits fit better with surgical operations and cost less.This review summarizes the merits and demerits of different ways to produce glaucomatous rabbit models,such as intracameral injection,vortex vein obstruction,Trendelenburg position,laser photo-coagulation,glucocorticoid induction,limbal buckling induction,retinal ischemia–reperfusion models,and spontaneous models.We analyzed their mechanisms in the hope of providing more references for experimental design and promoting the understanding of glaucoma treatment strategies.展开更多
Detecting cyber attacks in networks connected to the Internet of Things(IoT)is of utmost importance because of the growing vulnerabilities in the smart environment.Conventional models,such as Naive Bayes and support v...Detecting cyber attacks in networks connected to the Internet of Things(IoT)is of utmost importance because of the growing vulnerabilities in the smart environment.Conventional models,such as Naive Bayes and support vector machine(SVM),as well as ensemble methods,such as Gradient Boosting and eXtreme gradient boosting(XGBoost),are often plagued by high computational costs,which makes it challenging for them to perform real-time detection.In this regard,we suggested an attack detection approach that integrates Visual Geometry Group 16(VGG16),Artificial Rabbits Optimizer(ARO),and Random Forest Model to increase detection accuracy and operational efficiency in Internet of Things(IoT)networks.In the suggested model,the extraction of features from malware pictures was accomplished with the help of VGG16.The prediction process is carried out by the random forest model using the extracted features from the VGG16.Additionally,ARO is used to improve the hyper-parameters of the random forest model of the random forest.With an accuracy of 96.36%,the suggested model outperforms the standard models in terms of accuracy,F1-score,precision,and recall.The comparative research highlights our strategy’s success,which improves performance while maintaining a lower computational cost.This method is ideal for real-time applications,but it is effective.展开更多
Animal models are extensively used in all aspects of biomedical research,with substantial contributions to our understanding of diseases,the development of pharmaceuticals,and the exploration of gene functions.The fie...Animal models are extensively used in all aspects of biomedical research,with substantial contributions to our understanding of diseases,the development of pharmaceuticals,and the exploration of gene functions.The field of genome modification in rabbits has progressed slowly.However,recent advancements,particularly in CRISPR/Cas9-related technologies,have catalyzed the successful development of various genome-edited rabbit models to mimic diverse diseases,including cardiovascular disorders,immunodeficiencies,agingrelated ailments,neurological diseases,and ophthalmic pathologies.These models hold great promise in advancing biomedical research due to their closer physiological and biochemical resemblance to humans compared to mice.This review aims to summarize the novel gene-editing approaches currently available for rabbits and present the applications and prospects of such models in biomedicine,underscoring their impact and future potential in translational medicine.展开更多
Artificial rabbits optimization(ARO)is a recently proposed biology-based optimization algorithm inspired by the detour foraging and random hiding behavior of rabbits in nature.However,for solving optimization problems...Artificial rabbits optimization(ARO)is a recently proposed biology-based optimization algorithm inspired by the detour foraging and random hiding behavior of rabbits in nature.However,for solving optimization problems,the ARO algorithm shows slow convergence speed and can fall into local minima.To overcome these drawbacks,this paper proposes chaotic opposition-based learning ARO(COARO),an improved version of the ARO algorithm that incorporates opposition-based learning(OBL)and chaotic local search(CLS)techniques.By adding OBL to ARO,the convergence speed of the algorithm increases and it explores the search space better.Chaotic maps in CLS provide rapid convergence by scanning the search space efficiently,since their ergodicity and non-repetitive properties.The proposed COARO algorithm has been tested using thirty-three distinct benchmark functions.The outcomes have been compared with the most recent optimization algorithms.Additionally,the COARO algorithm’s problem-solving capabilities have been evaluated using six different engineering design problems and compared with various other algorithms.This study also introduces a binary variant of the continuous COARO algorithm,named BCOARO.The performance of BCOARO was evaluated on the breast cancer dataset.The effectiveness of BCOARO has been compared with different feature selection algorithms.The proposed BCOARO outperforms alternative algorithms,according to the findings obtained for real applications in terms of accuracy performance,and fitness value.Extensive experiments show that the COARO and BCOARO algorithms achieve promising results compared to other metaheuristic algorithms.展开更多
reconstituted embryos were produced by nuclear transplantation using bovine ear fibroblasts at G 0 or non-G 0 stage as donor nuclei and oocytes collected from superovulated multiparous or young rabbits as recipi...reconstituted embryos were produced by nuclear transplantation using bovine ear fibroblasts at G 0 or non-G 0 stage as donor nuclei and oocytes collected from superovulated multiparous or young rabbits as recipients. After cultivation in two kinds of medium M199+10%FBS or RD+10%FBS, 112 of them developed to 2-cell stage (62.2%) and 26 to morula stage (14.4%) and 20 of them eventually developed to blastocyst stage (11.1%). There is no significant difference for the cleavage rates in two groups of reconstituted embryos derived from G 0 -stage and non-G 0 stage donor cells respectively. However, G 0-stage donor cells could result in higher rate of 8-cell16-cell stage embryos significantly (P<0.05), as well as higher rate of blastocysts (P<0.01). It seems that using two different culture systems had no significant effects on the cleavage rate, morula rate or blastocyst rate (P>0.05).展开更多
A study conducted on burgundy rabbits evaluated the effects of rations containing mango (Mangifera indica), avocado (Persea americana) and guava (Psidium guajava) powder. For this purpose, 36 rabbits (20 males and 16 ...A study conducted on burgundy rabbits evaluated the effects of rations containing mango (Mangifera indica), avocado (Persea americana) and guava (Psidium guajava) powder. For this purpose, 36 rabbits (20 males and 16 females) aged 60 to 70 days with an average weight of 1012 ± 133 g were divided randomly into 4 equal groups (T0, T1, T2 and T3) of 9 animals each according to body weight (bw). The rabbits were divided throughout the trial, the animals were fed, those of group T0 (control) with a standard feed without any type of leaf powder, while those of groups 1, 2 and 3 received the standard feed supplemented with Mangifera indica, Persea americana and Psidium guajava leaves powder at the rate of 0.5% respectively. After two months of treatment, the animals were fasted for 12 hours (20 h - 8 h) and sacrificed to evaluate carcass and digestive organ weights. The results revealed that the values of feed intake, live weight and weight gain were non-significantly (p > 0.05) increased in all animals regardless of the ration in reference to the control. The different leaves powder induced an increase in carcass yield in rabbits but this increase was only significant (p M. indica leaf powder (51.03 ± 0.24) as compared to the control (48.63 ± 0.74). Gut length was significantly increased in animals fed rations containing Psidium guajava and Persea americana leaves powder compared to the control. A significant increase in gut weight was observed in animals fed the Persea americana leaf supplemented ration. In general, mango leaf powder performed better than other types of powders.展开更多
Background The aim of this experiment was to investigate the effect of different levels of betaine(Bet)inclusion in the diet on the intestinal health of growing rabbits under summer heat.A total of 100 weaned Qixing m...Background The aim of this experiment was to investigate the effect of different levels of betaine(Bet)inclusion in the diet on the intestinal health of growing rabbits under summer heat.A total of 100 weaned Qixing meat rabbits aged 35 d with body weight of 748.61±38.59 g were randomly divided into 5 treatment groups:control group(basal diet)and Bet groups(basal diet+0.75,1.0,1.5 or 2.0 g/kg Bet).The average daily temperature in the rabbitry during the experiment was 30.48°C and the relative humidity was 69.44%.Results Dietary addition of Bet had no significant effect on growth performance and health status of growing rabbits(P>0.05),but it increased ileal secretory immunoglobulin A content compared to the control under summer heat(P<0.05).Addition of 0.75 g/kg Bet up-regulated jejunal IL-4,down-regulated ileal TNF-αexpression(P<0.05).The addition of 1.0 g/kg Bet increased the villi height(VH)in the jejunum(P<0.05).Serum glucose levels were reduced,and the expression of SLC6A20 was up-regulated in jejunum and ileum of rabbits fed with 1.5 g/kg Bet(P<0.05).When added at 2.0 g/kg,Bet reduced serum HSP70 content,increased jejunal VH,and up-regulated duodenal SLC7A6,SLC38A2,mTOR and 4EBP-2 expression(P<0.05).Correlation analysis revealed that intestinal mTOR expression was significantly and positively correlated with SLC7A6,SLC38A2,SLC36A1 and IL-4 expression(P<0.05).Conclusions Dietary addition of Bet can up-regulate the expression of anti-inflammatory factors through the AAT/mTOR pathway,improve the intestinal immune function,alleviate intestinal damage in growing rabbits caused by summer heat,and improve intestinal health.展开更多
Factors affecting the efficiency of nuclear transfer (NT) in rabbits were examined in the present study. When 100 V mm of pulse strength and 15 us of pulse duration were employed, 3 and 4 electronic pulses resulted ...Factors affecting the efficiency of nuclear transfer (NT) in rabbits were examined in the present study. When 100 V mm of pulse strength and 15 us of pulse duration were employed, 3 and 4 electronic pulses resulted in significantly more cytoplasts fused with donor cells compared with 2 electronic pulses (P〈 0.05), but no significant difference was found in the cleavage rate of reconstructed embryos among the three groups (P〉0.05). When the duration and number of electronic pulse were fixed at 15 ps and 3 times, increase of pulse intensity from 100 V mm 1 to 150 V mm^-1 and 200 V mm^-1 resulted in a significantly decrease in the cleavage rate of reconstructed embryos (P〈 0.05), although the fusion rate did not significantly differ among the three groups (P〉 0.05). Significantly more reconstructed embryos cleaved and developed to blastocysts when they were derived from donor embryos at the 8-16-cell stage, in comparison with the reconstructed embryos derived from donor embryos at the compact morula stage (P 〈 0.05), although the fusion rate was similar (P 〉 0.05). Activation of cytoplasts prior to fusion increased the cleavage rate (P〈 0.05) and blastocyst development (P〈 0.05) of reconstructed embryos, but decreased the fusion rate (P 〈 0.05) compared with cytoplasts activated post fusion. More reconstructed embryos developed to blastocysts when they were cultured in TCM + 3% OCS at the first 48 h and then cultured in TCM199+ 10% FCS, in comparison with the reconstructed embryos cultured in either TCM199+ 10% FCS or TCM199+3% OCS (P 〈 0.05). When 22 NT embryos were transferred into the oviducts of one recipient rabbit, one recipient rabbit delivered a female rabbit at 34 days of gestation. In conclusion, either electrofusion parameter or developmental stage of donor embryos have a significant effect on the efficiency of NT, NT embryos require different concentration of serum at their different development stages.展开更多
BACKGROUND Tuberculosis is among the most devastating infectious diseases worldwide.Spinal tuberculosis is not easy to detect at an early stage,which without effective treatment often leads to spinal deformity and spi...BACKGROUND Tuberculosis is among the most devastating infectious diseases worldwide.Spinal tuberculosis is not easy to detect at an early stage,which without effective treatment often leads to spinal deformity and spinal cord damage which in turn cause complications such as paraplegia and quadriplegia.In this study,we established a model using three concentrations of bacteria and carried out a comprehensive evaluation of the model by imaging,general observations,and histopathological and bacteriological studies.AIM To establish a rabbit model of spinal tuberculosis and examine the effect on the model’s efficacy using different concentrations of Mycobacterium tuberculosis(M.tuberculosis)inoculum.METHODS New Zealand rabbits were randomly divided into experimental,control and blank groups.The experimental and control animals were sensitized with complete Freund′s adjuvant,a hole was drilled beneath the upper endplate of the L6 vertebral body and filled with gelfoam sponge.The experimental group was divided into three subgroups(experimental 1,experimental 2,experimental 3)and infused with M.tuberculosis suspension at various concentrations.The control group was inoculated with saline and the blank group received no treatment.The 12-week post-operative survival rates were 100%,80%and 30%in the experimental groups inoculated with concentrations of 106,107 and 108 CFU/mL bacteria,respectively.RESULTS The survival rate of the control and blank groups was 100%.Vertebral body destruction at 8 weeks in the three experimental groups as determined by X-ray analysis was 33.3%,62.5%and 66.7%,and by computed tomography(CT)and 3-dimensional CT 44.4%,75%and 100%,respectively.At 12 weeks,the figures were 44.4%,75%and 100%by X-ray analysis and 44.4%,100%and 100%by CT and 3-dimensional CT,respectively.All surviving rabbits of the experimental groups had vertebral destruction.The positive bacterial culture rates were 22.2%,75%and 66.7%,respectively,in the experimental groups.After being sensitized with complete Freund's adjuvant,large differences were observed in the extent of spinal tuberculosis after inoculation of the rabbits with different concentrations of H37RV standard M.tuberculosis.CONCLUSION The experimental 1 had a low success rate at establishing an infection.The experimental 3 resulted in high mortality and complication rates.The experimental 2 was optimum for establishing a spinal tuberculosis model based on the high level of symptoms observed and the low rabbit mortality.展开更多
Background Increased backfat thickness of sows in early gestation is negative to reproductive performance.Endometrial receptivity is an important determinant of reproductive success,but it is unclear whether the effec...Background Increased backfat thickness of sows in early gestation is negative to reproductive performance.Endometrial receptivity is an important determinant of reproductive success,but it is unclear whether the effect of sow backfat thickness on litter size is associated with endometrial receptivity and whether melatonin treatment may have benefits.The present study seeks to answer these questions through in vitro and in vivo investigations.Results Excessive lipid deposition and lower melatonin levels in the uterus are detrimental to endometrial receptivity and embryo implantation in high backfat thickness sows.In cells treated with melatonin,the MT2/PI3K/LIF axis played a role in reducing lipid accumulation in porcine endometrial epithelium cells and improved endometrial receptivity.Furthermore,we found a reduction of lipids in the uterus after eight weeks of intraperitoneal administration of melatonin to HFD mice.Notably,melatonin treatment caused a significant reduction in the deposition of endometrial collagen,an increase in the number of glands,and repair of the pinopode structure,ultimately improving endometrial receptivity,promoting embryo implantation,and increasing the number of litter size of mice.Conclusions Collectively,the finding reveals the harmful effects of high backfat thickness sows on embryo implantation and highlight the role of melatonin and the MT2/PI3K/LIF axis in improving endometrial receptivity by enhancing metabolism and reducing the levels of uterine lipids in obese animals.展开更多
The rapidly evolving environment of assisted reproductive technology(ART)requires consideration of how new innovations are reshaping clinical practice as much as research.In particular,there are three key areas that,w...The rapidly evolving environment of assisted reproductive technology(ART)requires consideration of how new innovations are reshaping clinical practice as much as research.In particular,there are three key areas that,while full of promise,also present significant challenges:the use of artificial intelligence(AI)in embryo selection,the impact of personalized medicine on ART success rates,and the ethical considerations of genetic screening of embryos[1].This letter is meant to provoke further discussion and highlight the need for harmonized global guidelines as these advances continue to reshape the reproductive medicine environment.展开更多
Objective:To evaluate the effect of glutathione(GSH)supplementation in maturation and adaptation media on oocyte development,embryo quality,and oocyte viability after vitrification.Methods:The GSH concentrations were ...Objective:To evaluate the effect of glutathione(GSH)supplementation in maturation and adaptation media on oocyte development,embryo quality,and oocyte viability after vitrification.Methods:The GSH concentrations were classified into four groups(0,0.5,1.0,and 1.5 mM)which were added to the maturation medium.The maturation process was conducted in vitro for 24 h.Following maturation,oocytes were fertilized with Bali bull semen for 5-6 h and then cultured for 48 h.The morphological quality of ocytes matured with GSH addition and the vitrification method used was evaluated.Parameters assessed included maturation rate,fertilization rate,embryo development,post-vitrification oocyte morphology,and quality of post-vitrification oocytes with GSH added to the adaptation medium.Results:The addition of GSH to the maturation medium significantly improved oocyte quality and embryo development(P<0.05).Specifically,adding 1.5 mM GSH increased the percentage of oocytes reaching metaphase栻from 57.6%without GSH oocytes to 79.0%with 1.5 mM GSH,two-pronuclei fertilization from 47.0%to 72.7%,embryo development from 37.1%to 57.2%,morula formation from 14.6%to 33.7%,and blastocyst formation from 8.1%to 23.8%.Additionally,the survival rate of oocytes post-vitrification increased to 75%with GSH supplementation.Conclusions:The addition of 0.5-1.5 mM of GSH to the maturation and adaptation media significantly enhanced the metaphase栻stage,fertilization rates,cleavage rates,and the survival of oocytes after vitrification.Among the concentrations of 1.5 mM was the most effective in increasing oocyte development and maintaining oocytes viability post-vitrification.展开更多
In grape breeding programs,the extensive planting of seedlings is a crucial aspect.However,grape seeds display distinct dormancy traits,necessitating a prolonged cold stratification process for dormancy release.In ord...In grape breeding programs,the extensive planting of seedlings is a crucial aspect.However,grape seeds display distinct dormancy traits,necessitating a prolonged cold stratification process for dormancy release.In order to enhance the efficiency of breeding programs,this study presents an innovative in vitro embryo germination technique that eliminates the requirement for cold stratification of seeds.The method involves the disruption of peripheral tissue in grape seed embryos using a straightforward mechanical technique,resulting in the efficient production of a substantial quantity of seed embryos,with a germination rate of up to 88% for these isolated embryos.These embryos are subsequently cultured in vitro to facilitate germination into seedlings,thereby eliminating the need for cold stratification.Consequently,grape seedlings can be obtained within a significantly reduced timeframe of 30-38 d,expediting the overall grape breeding process.This novel approach not only accelerates grape hybridization but also streamlines the selection of new grape varieties,contributing to an efficient and time-sensitive breeding methodology.展开更多
Inferior grains exhibit delayed developmental processes and reduced metabolic activities compared to superior grains,leading to unstable rice yield and quality.While significant advancements have been achieved in eluc...Inferior grains exhibit delayed developmental processes and reduced metabolic activities compared to superior grains,leading to unstable rice yield and quality.While significant advancements have been achieved in elucidating the physiology of endosperm filling in inferior grains,the role of the embryo remains underexplored and warrants comprehensive investigation.Two Wuyujing 3 mutants,DW024(relatively synchronous;syn-DW024)and DW179(significantly asynchronous;asyn-DW179),with different grain-filling patterns were used in this study.Samples of superior and inferior grains were collected at intervals from 5 to 60 d after fertilization and subsequently dissected into subsamples of the embryo and endosperm.Histochemical staining,biochemical analysis,and RNA sequencing(RNA-seq)were combined to systematically compare developmental and physiological traits between superior and inferior grains.Combining hierarchical clustering of mRNA datasets revealed three developmental phases of the endosperm and embryo:morphogenesis,endosperm filling/embryo enlargement,and maturation.In both syn-DW024 and asyn-DW179,the duration of the endosperm/embryo morphogenesis phase was identical in superior and inferior grains.The inferior grains of asyn-DW179 exhibited a 10-day prolongation in the endosperm filling phase and a 20-day extension in the embryo enlargement phase compared to the superior grains.The endosperm of inferior grains exhibited higher contents of sugars and free amino acids,along with slower accumulation of storage compounds,which was associated with the down-regulation of genes for starch synthesis and ABA signaling.In addition,transporters for nutrient exchanges between endosperm and embryo were down-regulated,suggesting a potential role of the embryo in adjusting the endosperm filling process.Collectively,our results reveal that the prolonged phases of endosperm filling and embryo enlargement may underlie the impaired development of inferior grains,offering a new perspective for breeding or cultivating rice with uniform grain quality.展开更多
Embryo size is a critical trait determining not only grain yield but also the nutrition of the maize kernel.Up to the present,only a few genes have been characterized affecting the maize embryo/kernel ratio.Here,we id...Embryo size is a critical trait determining not only grain yield but also the nutrition of the maize kernel.Up to the present,only a few genes have been characterized affecting the maize embryo/kernel ratio.Here,we identify 63 genes significantly associated with maize embryo/kernel weight ratio using a genome-wide association study(GWAS).The peak GWAS signal shows that the natural variation in Zea mays COMPACT PLANT2(CT2),encoding the heterotrimeric G proteinαsubunit,is significantly associated with the Embryo/Kernel Weight Ratio(EKWR).Further analyses show that a missense mutation of CT2 increases its enzyme activity and associates with EKWR.The function of CT2 on affecting embryo/kernel weight ratio is further validated by the characterization of two ct2 mutants,for which EKWR is significantly decreased.Subsequently,the key downstream genes of CT2 are identified by combining the differential expression analysis of the ct2 mutant and quantitative trait transcript analysis in the GWAS population.In addition,the allele frequency spectrum shows that CT2 was under selective pressure during maize domestication.This study provides important genetic insights into the natural variation of maize embryo/kernel weight ratio,which could be applied in future maize breeding programs to improve grain yield and nutritional content.展开更多
Background MicroRNAs(miRNAs)are presented in the uterine lumen of many mammals,and in vitro experiments have determined that several miRNAs are important for the regulation of endometrial and trophoblast functions.Our...Background MicroRNAs(miRNAs)are presented in the uterine lumen of many mammals,and in vitro experiments have determined that several miRNAs are important for the regulation of endometrial and trophoblast functions.Our aim was to identify and contrast the miRNAs present in extracellular vesicles(EVs)in the uterine lumen fluid(ULF)at the onset of attachment in cattle pregnancies(gestation d 18)initiated by artificial insemination(AI)or by the trans-fer of an in vitro-produced blastocyst(IVP-ET).A third group had no conceptus after the transfer of an IVP embryo.Results The abundance of 263 annotated miRNAs was quantified in the EVs collected from ULF.There was an increase in the transcript abundance of 20 miRNAs in the ULF EVs from the AI pregnant group,while 4 miRNAs had a lower abundance relative to the group not containing a conceptus.Additionally,4 miRNAs were more abun-dant in ULF EVs in the AI pregnant group relative to IVP-ET group(bta-mir-17,bta-mir-7-3,MIR7-1,MIR18A).Specific miRNAs in the ULF EVs were co-expressed with messenger RNAs expressed in extra-embryonic tissues and endome-trium,including genes that are known to be their targets.Conclusions The results provide biological insights into the participation of miRNAs in the regulation of trophoblast proliferation and differentiation,as well as in endometrium receptivity.The knowledge that in vitro cultured embryos can contribute to the altered abundance of specific miRNAs in the uterine lumen can lead to the development of cor-rective approaches to reduce conceptus losses during the first month of pregnancy in cattle.展开更多
Background:Diabetic retinal neuropathy(DRN)leads to significant visual impairment;however,no existing animal model fully replicates its neural alterations,and inconsistent induction protocols with high mortality rates...Background:Diabetic retinal neuropathy(DRN)leads to significant visual impairment;however,no existing animal model fully replicates its neural alterations,and inconsistent induction protocols with high mortality rates hinder long-term investigations.Methods:Adult male rabbits were randomly assigned to four experimental groups,each receiving a single intravenous injection of varying doses of alloxan and one control group.The safety and efficacy of alloxan in inducing diabetes were evaluated to determine the optimal dose.At 9 weeks following injection with alloxan,retinal function was assessed using full-field electroretinography(ERG)and visual evoked potentials(VEPs).Retinal structure was examined in rabbits using spectral-domain optical coherence tomography(SD-OCT),Optos ultra-widefield(Optos UWF)false-color imaging,and widefield fundus fluorescein angiography(WF-FFA).Results:Rabbits in the 80 mg/kg alloxan group exhibited fewer complications,lower mortality,and a higher model success rate compared to other groups.At 9 weeks post-injection,these rabbits demonstrated significantly elevated hemoglobin A1c and total cholesterol(p<0.05)relative to controls.ERG revealed statistically significant reductions in oscillatory potential and b-wave amplitudes(p<0.05),while VEP indicated decreased P2 amplitude(p<0.001)and prolonged P2 latency(p<0.05).SD-OCT,Optos UWF imaging,and WF-FFA demonstrated no significant changes in vascular abnormalities.Additionally,Hematoxylin and Eosin staining revealed retinal swelling(p<0.05),and immunofluorescence confirmed glial activation and neuronal loss.Conclusions:A single intravenous injection of 80 mg/kg alloxan effectively and safely induced DRN in rabbits,resulting in neural retina damage,thereby establishing this model as an ideal model for DRN research.展开更多
基金the Canadian Institutes of Health Research(CIHR),Grant/Award Number:PJT-175016the Fonds de recherche du Québec(FRQ)through the research centre grant for the CHU de Québec-UniversitéLaval Research Center,Grant/Award Number:30641+2 种基金the Quebec Cell,Tissue and Gene Therapy Network—ThéCellthe FRQS,the Fondation du CHU de Québec-UniversitéLavalNeuro Québec。
文摘Background:The absence of well-established immunosuppressed rabbit models poses a significant hurdle in xenograft experiments.Tacrolimus has been identified as a highly promising immunosuppressive agent for rabbits.However,determining the optimal dosage and route of administration to minimize toxicity while maintaining efficacy remains challenging.Methods:In this study,we investigated the effect of orally administered tacrolimus in rabbits,with an aim to achieve a whole blood target trough level of 3-10 ng/m L,and looked at signs of tissue rejection after the transplantation of a human nerve conduit to repair a severed fibular nerve.An oral dosage range of 0.25-1.5 mg/kg/d was studied for up to 1 year in 63 New Zealand rabbits.Results:We demonstrated the feasibility of long-term grafting in rabbits while maintaining safe immunosuppression,with side effects mainly limited to diarrhea.Customizing the administered dose proved crucial for graft efficacy and low toxicity,which translated into 100%individual survival.We suggest an oral tacrolimus dose of 1.0-1.5 mg/kg depending on individual heterogeneity and recommend to implement a close therapeutic drug monitoring in the rabbits to maintain a whole blood tacrolimus trough level within the range of 5-12 ng/m L,as levels below 5 ng/m L showed signs of inflammation in the graft.Conclusion:The oral administration of tacrolimus enabled efficient immunosuppression of rabbits over a 1-year period without significant side effects or loss of animals.
基金supported by the Jilin Provincial Department of Education Science and Technology Research Project(JJKH20231141K)Natural Science Foundation of Jilin Province of China(20230101154JC)Young Elite Scientists Sponsorship Program by CAST(2022QNRC001)。
文摘Chronic pancreatitis(CP)is a progressive and irreversible fibroinflammatory disease that markedly increases susceptibility to pancreatic cancer and remains without effective targeted therapies.Among the genetic contributors to CP,the carboxypeptidase A1 p.Ser282Pro(CPA1^(S282P))variant has been proposed to promote disease through misfolding-induced endoplasmic reticulum stress(ERS),although the broader pathogenic landscape remains incompletely defined.This study generated a rabbit model mimicking the human CPA1S282P mutation using the SpRY-ABE-8.17 system.Homozygous CPA1^(S282P)rabbits exhibited characteristic human CP phenotypes following alcohol induction,including visceral pain,elevated serum lipase and amylase,inflammatory cell infiltration,and extensive pancreatic fibrosis.Biochemical analyses confirmed that the p.S282P mutation induced CPA1 misfolding and elevated the expression of ERS markers GRP78 and CHOP in both transfected HEK293T cells and homozygous mutant rabbits.Notably,the CPA1^(S282P)mutation markedly disrupted intra-pancreatic lipid homeostasis,contributing to the development of CP in mutant rabbits.This study successfully established the first rabbit model of CP that accurately recapitulates CP caused by a defined human point mutation.Additionally,this study provides insights into a previously unrecognized link between CPA1 and intra-pancreatic lipid metabolism,offering a foundation for identifying novel therapeutic targets for human CP.
基金The 64th batch of China Postdoctoral Science Foundation,Grant/Award Number:2018M640754National Natural Science Foundation of China,Grant/Award Number:81860870The“Wang Heng xin Scientific Research Fund”project of Hunan University of Chinese Medicine,Grant/Award Number:2023HX007。
文摘Glaucoma,a visual thief,is characterized by elevated intraocular pressure(IOP)and the loss of retinal ganglion cells(RGCs).Selecting suitable animals for preclinical models is of great significance in research on the prevention,early screening,and effective treatments of glaucoma.Rabbit eyeballs possess similar vascularity and aqueous humor outflow pathways to those of humans.Thus,they are among the earliest in vivo models used in glaucoma research.Over the years,rabbit models have made substantial contributions to understanding glaucomatous pathophysiology,surgical adaptations,biomedical device development,and drug development for reducing IOP,protecting RGCs,and inhibiting fibrosis.Compared to other animals,rabbits fit better with surgical operations and cost less.This review summarizes the merits and demerits of different ways to produce glaucomatous rabbit models,such as intracameral injection,vortex vein obstruction,Trendelenburg position,laser photo-coagulation,glucocorticoid induction,limbal buckling induction,retinal ischemia–reperfusion models,and spontaneous models.We analyzed their mechanisms in the hope of providing more references for experimental design and promoting the understanding of glaucoma treatment strategies.
基金funded by Institutional Fund Projects under grant no.(IFPDP-261-22)。
文摘Detecting cyber attacks in networks connected to the Internet of Things(IoT)is of utmost importance because of the growing vulnerabilities in the smart environment.Conventional models,such as Naive Bayes and support vector machine(SVM),as well as ensemble methods,such as Gradient Boosting and eXtreme gradient boosting(XGBoost),are often plagued by high computational costs,which makes it challenging for them to perform real-time detection.In this regard,we suggested an attack detection approach that integrates Visual Geometry Group 16(VGG16),Artificial Rabbits Optimizer(ARO),and Random Forest Model to increase detection accuracy and operational efficiency in Internet of Things(IoT)networks.In the suggested model,the extraction of features from malware pictures was accomplished with the help of VGG16.The prediction process is carried out by the random forest model using the extracted features from the VGG16.Additionally,ARO is used to improve the hyper-parameters of the random forest model of the random forest.With an accuracy of 96.36%,the suggested model outperforms the standard models in terms of accuracy,F1-score,precision,and recall.The comparative research highlights our strategy’s success,which improves performance while maintaining a lower computational cost.This method is ideal for real-time applications,but it is effective.
基金supported by the National Natural Science Foundation of China (31970574)。
文摘Animal models are extensively used in all aspects of biomedical research,with substantial contributions to our understanding of diseases,the development of pharmaceuticals,and the exploration of gene functions.The field of genome modification in rabbits has progressed slowly.However,recent advancements,particularly in CRISPR/Cas9-related technologies,have catalyzed the successful development of various genome-edited rabbit models to mimic diverse diseases,including cardiovascular disorders,immunodeficiencies,agingrelated ailments,neurological diseases,and ophthalmic pathologies.These models hold great promise in advancing biomedical research due to their closer physiological and biochemical resemblance to humans compared to mice.This review aims to summarize the novel gene-editing approaches currently available for rabbits and present the applications and prospects of such models in biomedicine,underscoring their impact and future potential in translational medicine.
基金funded by Firat University Scientific Research Projects Management Unit for the scientific research project of Feyza AltunbeyÖzbay,numbered MF.23.49.
文摘Artificial rabbits optimization(ARO)is a recently proposed biology-based optimization algorithm inspired by the detour foraging and random hiding behavior of rabbits in nature.However,for solving optimization problems,the ARO algorithm shows slow convergence speed and can fall into local minima.To overcome these drawbacks,this paper proposes chaotic opposition-based learning ARO(COARO),an improved version of the ARO algorithm that incorporates opposition-based learning(OBL)and chaotic local search(CLS)techniques.By adding OBL to ARO,the convergence speed of the algorithm increases and it explores the search space better.Chaotic maps in CLS provide rapid convergence by scanning the search space efficiently,since their ergodicity and non-repetitive properties.The proposed COARO algorithm has been tested using thirty-three distinct benchmark functions.The outcomes have been compared with the most recent optimization algorithms.Additionally,the COARO algorithm’s problem-solving capabilities have been evaluated using six different engineering design problems and compared with various other algorithms.This study also introduces a binary variant of the continuous COARO algorithm,named BCOARO.The performance of BCOARO was evaluated on the breast cancer dataset.The effectiveness of BCOARO has been compared with different feature selection algorithms.The proposed BCOARO outperforms alternative algorithms,according to the findings obtained for real applications in terms of accuracy performance,and fitness value.Extensive experiments show that the COARO and BCOARO algorithms achieve promising results compared to other metaheuristic algorithms.
基金The research was supported by a Key Project of the“Tenth Five-Year”Science&Technology Development Plan(01606006)from Natural Science Foundation of Anhui Province,China.
文摘reconstituted embryos were produced by nuclear transplantation using bovine ear fibroblasts at G 0 or non-G 0 stage as donor nuclei and oocytes collected from superovulated multiparous or young rabbits as recipients. After cultivation in two kinds of medium M199+10%FBS or RD+10%FBS, 112 of them developed to 2-cell stage (62.2%) and 26 to morula stage (14.4%) and 20 of them eventually developed to blastocyst stage (11.1%). There is no significant difference for the cleavage rates in two groups of reconstituted embryos derived from G 0 -stage and non-G 0 stage donor cells respectively. However, G 0-stage donor cells could result in higher rate of 8-cell16-cell stage embryos significantly (P<0.05), as well as higher rate of blastocysts (P<0.01). It seems that using two different culture systems had no significant effects on the cleavage rate, morula rate or blastocyst rate (P>0.05).
文摘A study conducted on burgundy rabbits evaluated the effects of rations containing mango (Mangifera indica), avocado (Persea americana) and guava (Psidium guajava) powder. For this purpose, 36 rabbits (20 males and 16 females) aged 60 to 70 days with an average weight of 1012 ± 133 g were divided randomly into 4 equal groups (T0, T1, T2 and T3) of 9 animals each according to body weight (bw). The rabbits were divided throughout the trial, the animals were fed, those of group T0 (control) with a standard feed without any type of leaf powder, while those of groups 1, 2 and 3 received the standard feed supplemented with Mangifera indica, Persea americana and Psidium guajava leaves powder at the rate of 0.5% respectively. After two months of treatment, the animals were fasted for 12 hours (20 h - 8 h) and sacrificed to evaluate carcass and digestive organ weights. The results revealed that the values of feed intake, live weight and weight gain were non-significantly (p > 0.05) increased in all animals regardless of the ration in reference to the control. The different leaves powder induced an increase in carcass yield in rabbits but this increase was only significant (p M. indica leaf powder (51.03 ± 0.24) as compared to the control (48.63 ± 0.74). Gut length was significantly increased in animals fed rations containing Psidium guajava and Persea americana leaves powder compared to the control. A significant increase in gut weight was observed in animals fed the Persea americana leaf supplemented ration. In general, mango leaf powder performed better than other types of powders.
文摘Background The aim of this experiment was to investigate the effect of different levels of betaine(Bet)inclusion in the diet on the intestinal health of growing rabbits under summer heat.A total of 100 weaned Qixing meat rabbits aged 35 d with body weight of 748.61±38.59 g were randomly divided into 5 treatment groups:control group(basal diet)and Bet groups(basal diet+0.75,1.0,1.5 or 2.0 g/kg Bet).The average daily temperature in the rabbitry during the experiment was 30.48°C and the relative humidity was 69.44%.Results Dietary addition of Bet had no significant effect on growth performance and health status of growing rabbits(P>0.05),but it increased ileal secretory immunoglobulin A content compared to the control under summer heat(P<0.05).Addition of 0.75 g/kg Bet up-regulated jejunal IL-4,down-regulated ileal TNF-αexpression(P<0.05).The addition of 1.0 g/kg Bet increased the villi height(VH)in the jejunum(P<0.05).Serum glucose levels were reduced,and the expression of SLC6A20 was up-regulated in jejunum and ileum of rabbits fed with 1.5 g/kg Bet(P<0.05).When added at 2.0 g/kg,Bet reduced serum HSP70 content,increased jejunal VH,and up-regulated duodenal SLC7A6,SLC38A2,mTOR and 4EBP-2 expression(P<0.05).Correlation analysis revealed that intestinal mTOR expression was significantly and positively correlated with SLC7A6,SLC38A2,SLC36A1 and IL-4 expression(P<0.05).Conclusions Dietary addition of Bet can up-regulate the expression of anti-inflammatory factors through the AAT/mTOR pathway,improve the intestinal immune function,alleviate intestinal damage in growing rabbits caused by summer heat,and improve intestinal health.
文摘Factors affecting the efficiency of nuclear transfer (NT) in rabbits were examined in the present study. When 100 V mm of pulse strength and 15 us of pulse duration were employed, 3 and 4 electronic pulses resulted in significantly more cytoplasts fused with donor cells compared with 2 electronic pulses (P〈 0.05), but no significant difference was found in the cleavage rate of reconstructed embryos among the three groups (P〉0.05). When the duration and number of electronic pulse were fixed at 15 ps and 3 times, increase of pulse intensity from 100 V mm 1 to 150 V mm^-1 and 200 V mm^-1 resulted in a significantly decrease in the cleavage rate of reconstructed embryos (P〈 0.05), although the fusion rate did not significantly differ among the three groups (P〉 0.05). Significantly more reconstructed embryos cleaved and developed to blastocysts when they were derived from donor embryos at the 8-16-cell stage, in comparison with the reconstructed embryos derived from donor embryos at the compact morula stage (P 〈 0.05), although the fusion rate was similar (P 〉 0.05). Activation of cytoplasts prior to fusion increased the cleavage rate (P〈 0.05) and blastocyst development (P〈 0.05) of reconstructed embryos, but decreased the fusion rate (P 〈 0.05) compared with cytoplasts activated post fusion. More reconstructed embryos developed to blastocysts when they were cultured in TCM + 3% OCS at the first 48 h and then cultured in TCM199+ 10% FCS, in comparison with the reconstructed embryos cultured in either TCM199+ 10% FCS or TCM199+3% OCS (P 〈 0.05). When 22 NT embryos were transferred into the oviducts of one recipient rabbit, one recipient rabbit delivered a female rabbit at 34 days of gestation. In conclusion, either electrofusion parameter or developmental stage of donor embryos have a significant effect on the efficiency of NT, NT embryos require different concentration of serum at their different development stages.
基金Supported by Lanzhou City Science and Technology Development Guiding Plan Project,No.2023-ZD-170Lanzhou Science and Technology Plan Project,No.2023-2-11High-Level Talent Training Project At the 940th Hospital of the Joint Logistics Force,No.2024-G3-5.
文摘BACKGROUND Tuberculosis is among the most devastating infectious diseases worldwide.Spinal tuberculosis is not easy to detect at an early stage,which without effective treatment often leads to spinal deformity and spinal cord damage which in turn cause complications such as paraplegia and quadriplegia.In this study,we established a model using three concentrations of bacteria and carried out a comprehensive evaluation of the model by imaging,general observations,and histopathological and bacteriological studies.AIM To establish a rabbit model of spinal tuberculosis and examine the effect on the model’s efficacy using different concentrations of Mycobacterium tuberculosis(M.tuberculosis)inoculum.METHODS New Zealand rabbits were randomly divided into experimental,control and blank groups.The experimental and control animals were sensitized with complete Freund′s adjuvant,a hole was drilled beneath the upper endplate of the L6 vertebral body and filled with gelfoam sponge.The experimental group was divided into three subgroups(experimental 1,experimental 2,experimental 3)and infused with M.tuberculosis suspension at various concentrations.The control group was inoculated with saline and the blank group received no treatment.The 12-week post-operative survival rates were 100%,80%and 30%in the experimental groups inoculated with concentrations of 106,107 and 108 CFU/mL bacteria,respectively.RESULTS The survival rate of the control and blank groups was 100%.Vertebral body destruction at 8 weeks in the three experimental groups as determined by X-ray analysis was 33.3%,62.5%and 66.7%,and by computed tomography(CT)and 3-dimensional CT 44.4%,75%and 100%,respectively.At 12 weeks,the figures were 44.4%,75%and 100%by X-ray analysis and 44.4%,100%and 100%by CT and 3-dimensional CT,respectively.All surviving rabbits of the experimental groups had vertebral destruction.The positive bacterial culture rates were 22.2%,75%and 66.7%,respectively,in the experimental groups.After being sensitized with complete Freund's adjuvant,large differences were observed in the extent of spinal tuberculosis after inoculation of the rabbits with different concentrations of H37RV standard M.tuberculosis.CONCLUSION The experimental 1 had a low success rate at establishing an infection.The experimental 3 resulted in high mortality and complication rates.The experimental 2 was optimum for establishing a spinal tuberculosis model based on the high level of symptoms observed and the low rabbit mortality.
基金supported by the China Agriculture Research System(CARS-35-PIG)the National Natural Science Foundation of China(32272847,U22A20516)+1 种基金the National Key Research and Development Program of China(No.2021YFF1000602)the Key Research and Development Program of Shaanxi Province(No.2022ZDLNY01–04)。
文摘Background Increased backfat thickness of sows in early gestation is negative to reproductive performance.Endometrial receptivity is an important determinant of reproductive success,but it is unclear whether the effect of sow backfat thickness on litter size is associated with endometrial receptivity and whether melatonin treatment may have benefits.The present study seeks to answer these questions through in vitro and in vivo investigations.Results Excessive lipid deposition and lower melatonin levels in the uterus are detrimental to endometrial receptivity and embryo implantation in high backfat thickness sows.In cells treated with melatonin,the MT2/PI3K/LIF axis played a role in reducing lipid accumulation in porcine endometrial epithelium cells and improved endometrial receptivity.Furthermore,we found a reduction of lipids in the uterus after eight weeks of intraperitoneal administration of melatonin to HFD mice.Notably,melatonin treatment caused a significant reduction in the deposition of endometrial collagen,an increase in the number of glands,and repair of the pinopode structure,ultimately improving endometrial receptivity,promoting embryo implantation,and increasing the number of litter size of mice.Conclusions Collectively,the finding reveals the harmful effects of high backfat thickness sows on embryo implantation and highlight the role of melatonin and the MT2/PI3K/LIF axis in improving endometrial receptivity by enhancing metabolism and reducing the levels of uterine lipids in obese animals.
文摘The rapidly evolving environment of assisted reproductive technology(ART)requires consideration of how new innovations are reshaping clinical practice as much as research.In particular,there are three key areas that,while full of promise,also present significant challenges:the use of artificial intelligence(AI)in embryo selection,the impact of personalized medicine on ART success rates,and the ethical considerations of genetic screening of embryos[1].This letter is meant to provoke further discussion and highlight the need for harmonized global guidelines as these advances continue to reshape the reproductive medicine environment.
基金This study was financially supported by Universitas Hasanuddin through Penelitian Fundamental Kolaboratif(PFK)(letter of appointment number:00323/UN4.22/PT.0103/2023).
文摘Objective:To evaluate the effect of glutathione(GSH)supplementation in maturation and adaptation media on oocyte development,embryo quality,and oocyte viability after vitrification.Methods:The GSH concentrations were classified into four groups(0,0.5,1.0,and 1.5 mM)which were added to the maturation medium.The maturation process was conducted in vitro for 24 h.Following maturation,oocytes were fertilized with Bali bull semen for 5-6 h and then cultured for 48 h.The morphological quality of ocytes matured with GSH addition and the vitrification method used was evaluated.Parameters assessed included maturation rate,fertilization rate,embryo development,post-vitrification oocyte morphology,and quality of post-vitrification oocytes with GSH added to the adaptation medium.Results:The addition of GSH to the maturation medium significantly improved oocyte quality and embryo development(P<0.05).Specifically,adding 1.5 mM GSH increased the percentage of oocytes reaching metaphase栻from 57.6%without GSH oocytes to 79.0%with 1.5 mM GSH,two-pronuclei fertilization from 47.0%to 72.7%,embryo development from 37.1%to 57.2%,morula formation from 14.6%to 33.7%,and blastocyst formation from 8.1%to 23.8%.Additionally,the survival rate of oocytes post-vitrification increased to 75%with GSH supplementation.Conclusions:The addition of 0.5-1.5 mM of GSH to the maturation and adaptation media significantly enhanced the metaphase栻stage,fertilization rates,cleavage rates,and the survival of oocytes after vitrification.Among the concentrations of 1.5 mM was the most effective in increasing oocyte development and maintaining oocytes viability post-vitrification.
基金supported by Natural Science Foundation of Beijing Academy of Agriculture and Forestry Sciences(Grant No.QNJJ202301)the Youth Research Foundation of Institute of Forestry and Pomology+2 种基金Beijing Academy of Agriculture and Forestry Science(Grant No.LGJJ202202)the BAAFS Funding for the Development of Distinguished Scientist(Grant No.JKZX202402)the Beijing Natural Science Foundation(Grant No.6242019)。
文摘In grape breeding programs,the extensive planting of seedlings is a crucial aspect.However,grape seeds display distinct dormancy traits,necessitating a prolonged cold stratification process for dormancy release.In order to enhance the efficiency of breeding programs,this study presents an innovative in vitro embryo germination technique that eliminates the requirement for cold stratification of seeds.The method involves the disruption of peripheral tissue in grape seed embryos using a straightforward mechanical technique,resulting in the efficient production of a substantial quantity of seed embryos,with a germination rate of up to 88% for these isolated embryos.These embryos are subsequently cultured in vitro to facilitate germination into seedlings,thereby eliminating the need for cold stratification.Consequently,grape seedlings can be obtained within a significantly reduced timeframe of 30-38 d,expediting the overall grape breeding process.This novel approach not only accelerates grape hybridization but also streamlines the selection of new grape varieties,contributing to an efficient and time-sensitive breeding methodology.
基金supported by the National Key Research and Development Program of China(2022YFD2300700)the National Natural Science Foundation of China(32201894)+1 种基金Hainan Provincial Natural Science Foundation of China(323QN193)Rothamsted Research receives strategic funding from the Biotechnological and Biological Sciences Research Council of the UK.Matthew J.Paul acknowledges funding from the Delivering Sustainable Wheat(BB/X011003/1)Strategic Program.
文摘Inferior grains exhibit delayed developmental processes and reduced metabolic activities compared to superior grains,leading to unstable rice yield and quality.While significant advancements have been achieved in elucidating the physiology of endosperm filling in inferior grains,the role of the embryo remains underexplored and warrants comprehensive investigation.Two Wuyujing 3 mutants,DW024(relatively synchronous;syn-DW024)and DW179(significantly asynchronous;asyn-DW179),with different grain-filling patterns were used in this study.Samples of superior and inferior grains were collected at intervals from 5 to 60 d after fertilization and subsequently dissected into subsamples of the embryo and endosperm.Histochemical staining,biochemical analysis,and RNA sequencing(RNA-seq)were combined to systematically compare developmental and physiological traits between superior and inferior grains.Combining hierarchical clustering of mRNA datasets revealed three developmental phases of the endosperm and embryo:morphogenesis,endosperm filling/embryo enlargement,and maturation.In both syn-DW024 and asyn-DW179,the duration of the endosperm/embryo morphogenesis phase was identical in superior and inferior grains.The inferior grains of asyn-DW179 exhibited a 10-day prolongation in the endosperm filling phase and a 20-day extension in the embryo enlargement phase compared to the superior grains.The endosperm of inferior grains exhibited higher contents of sugars and free amino acids,along with slower accumulation of storage compounds,which was associated with the down-regulation of genes for starch synthesis and ABA signaling.In addition,transporters for nutrient exchanges between endosperm and embryo were down-regulated,suggesting a potential role of the embryo in adjusting the endosperm filling process.Collectively,our results reveal that the prolonged phases of endosperm filling and embryo enlargement may underlie the impaired development of inferior grains,offering a new perspective for breeding or cultivating rice with uniform grain quality.
基金supported by National Key Research and Development Program of China(2023YFF1000400)National Natural Science Foundation of China(32101693)+2 种基金Key Research and Development Program of Shaanxi(2021ZDLNY01-06)Agricultural Science and Technology Innovation Program of CAAS(CAAS-ZDRW202004)supported by Hatch project(1019088).
文摘Embryo size is a critical trait determining not only grain yield but also the nutrition of the maize kernel.Up to the present,only a few genes have been characterized affecting the maize embryo/kernel ratio.Here,we identify 63 genes significantly associated with maize embryo/kernel weight ratio using a genome-wide association study(GWAS).The peak GWAS signal shows that the natural variation in Zea mays COMPACT PLANT2(CT2),encoding the heterotrimeric G proteinαsubunit,is significantly associated with the Embryo/Kernel Weight Ratio(EKWR).Further analyses show that a missense mutation of CT2 increases its enzyme activity and associates with EKWR.The function of CT2 on affecting embryo/kernel weight ratio is further validated by the characterization of two ct2 mutants,for which EKWR is significantly decreased.Subsequently,the key downstream genes of CT2 are identified by combining the differential expression analysis of the ct2 mutant and quantitative trait transcript analysis in the GWAS population.In addition,the allele frequency spectrum shows that CT2 was under selective pressure during maize domestication.This study provides important genetic insights into the natural variation of maize embryo/kernel weight ratio,which could be applied in future maize breeding programs to improve grain yield and nutritional content.
基金Agriculture and Food Research Initiative Competitive Grant no.2018-67015-31936 from the USDA National Institute of Food and Agriculture.
文摘Background MicroRNAs(miRNAs)are presented in the uterine lumen of many mammals,and in vitro experiments have determined that several miRNAs are important for the regulation of endometrial and trophoblast functions.Our aim was to identify and contrast the miRNAs present in extracellular vesicles(EVs)in the uterine lumen fluid(ULF)at the onset of attachment in cattle pregnancies(gestation d 18)initiated by artificial insemination(AI)or by the trans-fer of an in vitro-produced blastocyst(IVP-ET).A third group had no conceptus after the transfer of an IVP embryo.Results The abundance of 263 annotated miRNAs was quantified in the EVs collected from ULF.There was an increase in the transcript abundance of 20 miRNAs in the ULF EVs from the AI pregnant group,while 4 miRNAs had a lower abundance relative to the group not containing a conceptus.Additionally,4 miRNAs were more abun-dant in ULF EVs in the AI pregnant group relative to IVP-ET group(bta-mir-17,bta-mir-7-3,MIR7-1,MIR18A).Specific miRNAs in the ULF EVs were co-expressed with messenger RNAs expressed in extra-embryonic tissues and endome-trium,including genes that are known to be their targets.Conclusions The results provide biological insights into the participation of miRNAs in the regulation of trophoblast proliferation and differentiation,as well as in endometrium receptivity.The knowledge that in vitro cultured embryos can contribute to the altered abundance of specific miRNAs in the uterine lumen can lead to the development of cor-rective approaches to reduce conceptus losses during the first month of pregnancy in cattle.
基金Key Project of Joint Special Funds for Applied Basic Research of Yunnan Provincial Department of Science and Technology Kunming Medical University,Grant/Award Number:2018FE001-(180)Clinical Research Center of the First People's Hospital of Yunnan Province,Grant/Award Number:2023YJZX-LN01+2 种基金Kunming University of Science and Technology School of Medicine Postgraduate Innovation FundResearch Plan of the National Natural Science Foundation of China,Grant/Award Number:82460210Provincial Key Clinical Specialty Platform of the First People's Hospital of Yunnan Province,Grant/Award Number:2024EKKFKT-04。
文摘Background:Diabetic retinal neuropathy(DRN)leads to significant visual impairment;however,no existing animal model fully replicates its neural alterations,and inconsistent induction protocols with high mortality rates hinder long-term investigations.Methods:Adult male rabbits were randomly assigned to four experimental groups,each receiving a single intravenous injection of varying doses of alloxan and one control group.The safety and efficacy of alloxan in inducing diabetes were evaluated to determine the optimal dose.At 9 weeks following injection with alloxan,retinal function was assessed using full-field electroretinography(ERG)and visual evoked potentials(VEPs).Retinal structure was examined in rabbits using spectral-domain optical coherence tomography(SD-OCT),Optos ultra-widefield(Optos UWF)false-color imaging,and widefield fundus fluorescein angiography(WF-FFA).Results:Rabbits in the 80 mg/kg alloxan group exhibited fewer complications,lower mortality,and a higher model success rate compared to other groups.At 9 weeks post-injection,these rabbits demonstrated significantly elevated hemoglobin A1c and total cholesterol(p<0.05)relative to controls.ERG revealed statistically significant reductions in oscillatory potential and b-wave amplitudes(p<0.05),while VEP indicated decreased P2 amplitude(p<0.001)and prolonged P2 latency(p<0.05).SD-OCT,Optos UWF imaging,and WF-FFA demonstrated no significant changes in vascular abnormalities.Additionally,Hematoxylin and Eosin staining revealed retinal swelling(p<0.05),and immunofluorescence confirmed glial activation and neuronal loss.Conclusions:A single intravenous injection of 80 mg/kg alloxan effectively and safely induced DRN in rabbits,resulting in neural retina damage,thereby establishing this model as an ideal model for DRN research.