Proper regulation of synapse formation and elimination is critical for establishing mature neuronal circuits and maintaining brain function.Synaptic abnormalities,such as defects in the density and morphology of posts...Proper regulation of synapse formation and elimination is critical for establishing mature neuronal circuits and maintaining brain function.Synaptic abnormalities,such as defects in the density and morphology of postsynaptic dendritic spines,underlie the pathology of various neuropsychiatric disorders.Protocadherin 17(PCDH17)is associated with major mood disorders,including bipolar disorder and depression.However,the molecular mechanisms by which PCDH17 regulates spine number,morphology,and behavior remain elusive.In this study,we found that PCDH17 functions at postsynaptic sites,restricting the number and size of dendritic spines in excitatory neurons.Selective overexpression of PCDH17 in the ventral hippocampal CA1 results in spine loss and anxiety-and depression-like behaviors in mice.Mechanistically,PCDH17 interacts with actin-relevant proteins and regulates actin filament(F-actin)organization.Specifically,PCDH17 binds to ROCK2,increasing its expression and subsequently enhancing the activity of downstream targets such as LIMK1 and the phosphorylation of cofilin serine-3(Ser3).Inhibition of ROCK2 activity with belumosudil(KD025)ameliorates the defective F-actin organization and spine structure induced by PCDH17 overexpression,suggesting that ROCK2 mediates the effects of PCDH17 on F-actin content and spine development.Hence,these findings reveal a novel mechanism by which PCDH17 regulates synapse development and behavior,providing pathological insights into the neurobiological basis of mood disorders.展开更多
Human brain development is a complex process,and animal models often have significant limitations.To address this,researchers have developed pluripotent stem cell-derived three-dimensional structures,known as brain-li...Human brain development is a complex process,and animal models often have significant limitations.To address this,researchers have developed pluripotent stem cell-derived three-dimensional structures,known as brain-like organoids,to more accurately model early human brain development and disease.To enable more consistent and intuitive reproduction of early brain development,in this study,we incorporated forebrain organoid culture technology into the traditional unguided method of brain organoid culture.This involved embedding organoids in matrigel for only 7 days during the rapid expansion phase of the neural epithelium and then removing them from the matrigel for further cultivation,resulting in a new type of human brain organoid system.This cerebral organoid system replicated the temporospatial characteristics of early human brain development,including neuroepithelium derivation,neural progenitor cell production and maintenance,neuron differentiation and migration,and cortical layer patterning and formation,providing more consistent and reproducible organoids for developmental modeling and toxicology testing.As a proof of concept,we applied the heavy metal cadmium to this newly improved organoid system to test whether it could be used to evaluate the neurotoxicity of environmental toxins.Brain organoids exposed to cadmium for 7 or 14 days manifested severe damage and abnormalities in their neurodevelopmental patterns,including bursts of cortical cell death and premature differentiation.Cadmium exposure caused progressive depletion of neural progenitor cells and loss of organoid integrity,accompanied by compensatory cell proliferation at ectopic locations.The convenience,flexibility,and controllability of this newly developed organoid platform make it a powerful and affordable alternative to animal models for use in neurodevelopmental,neurological,and neurotoxicological studies.展开更多
The sine oculis homeobox homolog(SIX)family,a group of transcription factors characterized by a conserved DNA-binding homology domain,plays a critical role in orchestrating embryonic development and organogenesis acro...The sine oculis homeobox homolog(SIX)family,a group of transcription factors characterized by a conserved DNA-binding homology domain,plays a critical role in orchestrating embryonic development and organogenesis across various organisms,including humans.Comprising six distinct members,from SIX1 to SIX6,each member contributes uniquely to the development and differentiation of diverse tissues and organs,underscoring the versatility of the SIX family.Dysregulation or mutations in SIX genes have been implicated in a spectrum of developmental disorders,as well as in tumor initiation and progression,highlighting their pivotal role in maintaining normal developmental trajectories and cellular functions.Efforts to target the transcriptional complex of the SIX gene family have emerged as a promising strategy to inhibit tumor development.While the development of inhibitors targeting this gene family is still in its early stages,the significant potential of such interventions holds promise for future therapeutic advances.Therefore,this review aimed to comprehensively explore the advancements in understanding the SIX family within gastrointestinal cancers,focusing on its critical role in normal organ development and its implications in gastrointestinal cancers,including gastric,pancreatic,colorectal cancer,and hepatocellular carcinomas.In conclusion,this review deepened the understanding of the functional roles of the SIX family and explored the potential of utilizing this gene family for the diagnosis,prognosis,and treatment of gastrointestinal cancers.展开更多
The organotypic retinal explant culture has been established for more than a decade and offers a range of unique advantages compared with in vivo experiments and cell cultures.However,the lack of systematic and contin...The organotypic retinal explant culture has been established for more than a decade and offers a range of unique advantages compared with in vivo experiments and cell cultures.However,the lack of systematic and continuous comparison between in vivo retinal development and the organotypic retinal explant culture makes this model controversial in postnatal retinal development studies.Thus,we aimed to verify the feasibility of using this model for postnatal retinal development studies by comparing it with the in vivo retina.In this study,we showed that postnatal retinal explants undergo normal development,and exhibit a consistent structure and timeline with retinas in vivo.Initially,we used SOX2 and PAX6 immunostaining to identify retinal progenitor cells.We then examined cell proliferation and migration by immunostaining with Ki-67 and doublecortin,respectively.Ki-67-and doublecortin-positive cells decreased in both in vivo and explants during postnatal retinogenesis,and exhibited a high degree of similarity in abundance and distribution between groups.Additionally,we used Ceh-10 homeodomain-containing homolog,glutamate-ammonia ligase(glutamine synthetase),neuronal nuclei,and ionized calcium-binding adapter molecule 1 immunostaining to examine the emergence of bipolar cells,Müller glia,mature neurons,and microglia,respectively.The timing and spatial patterns of the emergence of these cell types were remarkably consistent between in vivo and explant retinas.Our study showed that the organotypic retinal explant culture model had a high degree of consistency with the progression of in vivo early postnatal retina development.The findings confirm the accuracy and credibility of this model and support its use for long-term,systematic,and continuous observation.展开更多
The critical role of patient-reported outcome measures(PROMs)in enhancing clinical decision-making and promoting patient-centered care has gained a profound significance in scientific research.PROMs encapsulate a pati...The critical role of patient-reported outcome measures(PROMs)in enhancing clinical decision-making and promoting patient-centered care has gained a profound significance in scientific research.PROMs encapsulate a patient's health status directly from their perspective,encompassing various domains such as symptom severity,functional status,and overall quality of life.By integrating PROMs into routine clinical practice and research,healthcare providers can achieve a more nuanced understanding of patient experiences and tailor treatments accordingly.The deployment of PROMs supports dynamic patient-provider interactions,fostering better patient engagement and adherence to tre-atment plans.Moreover,PROMs are pivotal in clinical settings for monitoring disease progression and treatment efficacy,particularly in chronic and mental health conditions.However,challenges in implementing PROMs include data collection and management,integration into existing health systems,and acceptance by patients and providers.Overcoming these barriers necessitates technological advancements,policy development,and continuous education to enhance the acceptability and effectiveness of PROMs.The paper concludes with recommendations for future research and policy-making aimed at optimizing the use and impact of PROMs across healthcare settings.展开更多
Testicular development is an important biological process in male and requires interaction between the male germ cells and somatic cells.However,the mechanisms of testicular development in livestock,particularly in ca...Testicular development is an important biological process in male and requires interaction between the male germ cells and somatic cells.However,the mechanisms of testicular development in livestock,particularly in cattle,are poorly understood.Furthermore,cellular heterogeneity hinders the profiling of different cell types at different developmental stages.In this study,we first performed a single-cell transcriptomic study of the bovine testis development during puberty by using 10×genomics single-cell RNA sequencing(scRNA-seq).By collecting the scRNA-seq data from 11,083 cells from prepubertal and pubertal bovine testes,a high-resolution scRNA-seq atlas was described,identifying 9 somatic and 13 spermatogenic clusters.We also distinguished several stage-specific marker genes for bovine germ cells and somatic cells,such as GRAF2 and MORC1 for SSC(spermatogonial stem cells),HJURP and TCF19 for differentiating spermatogonia,ARSE for immature Sertoli,CLEC12B for mature Sertoli,LOC112441470 for Leydig.In conclusion,we have examined the transcription levels and constructed the single-cell developmental maps of germ cells and somatic cells during testicular development in Angus cattle.The datasets provided new insights into spermatogenesis and testicular somatic cell development in cattle.展开更多
Litchi (Litchi chinensis Sonn.) is a well-known tropical and subtropical woody fruit that originated from southern China (Wei et al.,2017;Hu et al.,2022).Based on the development of the embryo,litchi varieties can be ...Litchi (Litchi chinensis Sonn.) is a well-known tropical and subtropical woody fruit that originated from southern China (Wei et al.,2017;Hu et al.,2022).Based on the development of the embryo,litchi varieties can be divided into three distinct groups:large-seeded cultivars,small (abortive)-seeded cultivars and partial abortive-seeded cultivars.Seedless or the reduction in seed size due to embryo abortion is a desirable trait in fruit trees as it directly influences the texture and economic value of fleshy fruits,making small (abortive)-seeded litchi cultivars the most preferred.However,in current production practices,there is no efficient method available to induce or promote high seed abortion in litchi fruit.Therefore,understanding the stenospermy mechanisms of litchi seed development is of great significance for improving agricultural practices and managing genetic resources.展开更多
The enzyme C-14 sterol reductase is involved in biosynthesis of brassinosteroids(BR)and sterols,as well as plant development.OsFK1,a member of the sterol biosynthesis pathway located in the endoplasmic reticulum(ER),e...The enzyme C-14 sterol reductase is involved in biosynthesis of brassinosteroids(BR)and sterols,as well as plant development.OsFK1,a member of the sterol biosynthesis pathway located in the endoplasmic reticulum(ER),encodes C-14 sterol reductase.However,there is little research on the function of C-14 sterol reductase in rice.Compared with the wild type,an osfk1 mutant showed dwarf phenotype and premature aging in the second leaf during the trefoil stage,and abnormal development of leaf veins during the tillering stage.The osfk1 mutant showed signs of aberrant PCD,as evidenced by TUNEL staining.This suggested that high ROS buildup caused DNA damage and ROS-mediated cell death in the mutant.The osfk1 mutant also showed decreased chlorophyll content and aberrant chloroplast structure.Sequencing of the osfk1 mutant allele revealed a non-synonymous G to A mutation in the final intron,leading to early termination.Here,we identified the OsFK1 allele,cloned it by Mutmap sequencing,and verified it by complementation.HPLC-MS/MS assays demonstrated that the osfk1 mutation caused lower phytosterol levels.These findings showed that the OsFK1 allele encoding C-14 sterol reductase is involved in phytosterol biosynthesis and mediates normal development of rice plants.展开更多
Climate change is an alarming global challenge, particularly affecting the least developed countries (LDCs) including Liberia. These countries, located in regions prone to unpredictable temperature and precipitation c...Climate change is an alarming global challenge, particularly affecting the least developed countries (LDCs) including Liberia. These countries, located in regions prone to unpredictable temperature and precipitation changes, are facing significant challenges, particularly in climate-sensitive sectors such as mining and agriculture. LDCs need more resilience to adverse climate shocks but have limited capacity for adaptation compared to other developed and developing nations. This paper examines Liberia’s susceptibility to climate change as a least developed country, focusing on its exposure, sensitivity, and adaptive capacity. It provides an overview of LDCs and outlines the global distribution of carbon dioxide emissions. The paper also evaluates specific challenges that amplify Liberia’s vulnerability and constrain sustainable adaptation, providing insight into climate change’s existing and potential effects. The paper emphasizes the urgency of addressing climate impacts on Liberia and calls for concerted local and international efforts for effective and sustainable mitigation efforts. It provides recommendations for policy decisions and calls for further research on climate change mitigation and adaptation.展开更多
The hydraulic testing of pre-existing fractures(HTPF)is one of the most promising in situ stress measurement methods,particularly for three-dimensional stress tensor determination.However,the stress tensor determinati...The hydraulic testing of pre-existing fractures(HTPF)is one of the most promising in situ stress measurement methods,particularly for three-dimensional stress tensor determination.However,the stress tensor determination based on the HTPF method requires at least six tests or a minimum of 14-15 tests(under different conditions)for reliable results.In this study,we modified the HTPF method by considering the shear stress on each pre-existing fracture,which increased the number of equations for the stress tensor determination and decreased the number of tests required.Different shear stresses were attributed to different fractures by random sampling;therefore,the stress tensors were obtained by searching for the optimal solution using the least squares criterion based on the Monte Carlo method.Thereafter,we constrained the stress tensor based on the tensile strength criterion,compressive strength criterion,and vertical stress constraints.The inverted stress tensors were presented and analyzed based on the tensorial nature of the stress using the Euclidean mean stress tensor.Two stress-measurement campaigns in Weifang(Shandong Province,China)and Mercantour road tunnel(France)were implemented to highlight the validity and efficiency of the modified HTPF(M-HTPF)method.The results showed that the M-HTPF method can be applied for stress tensor inversion using only three to four tests on pre-existing fractures,neglecting the stress gradient.The inversion results were confined to relatively small distribution dispersions and were significantly reliable and stable due to the shear stresses on the fractures and the stress constraints employed.The M-HTPF method is highly feasible and efficient for complete stress tensor determination in a single borehole.展开更多
As a cell proliferation regulator involved in wide biological processes in plants,GRF-INTERACTING FACTOR(GIF)controls different tissues development.However,whether GIF participates in fruit development remains unclear...As a cell proliferation regulator involved in wide biological processes in plants,GRF-INTERACTING FACTOR(GIF)controls different tissues development.However,whether GIF participates in fruit development remains unclear.According to transcriptome data,we identified PbGIF1was highly expressed during fruit development in cytokinins induced parthenocarpy pear.In the present study,the biofunction of PbGIF1 was initially verified.Overexpression of PbGIF1 promoted fruit size of transgenic tomato.The size of flesh fruit was not affected by cell expansion but the cell proliferation was promoted by overexpressing Pb GIF1.The accelerated cell proliferation process was also observed in PbGIF1-overexpressed transgenic pear fruit calli.The transcriptional regulation of cytokinins on PbGIF1 was further confirmed by exogenous CPPU treatments in pear fruitlets.To investigate the underlying mechanism,the cytokinins-responded factor,PbRR1,was further focused on.The results of Yeast-one-hybrid assay suggested that PbRR1 can bind to the promoter sequence of PbGIF1.The transcriptional activation of PbRR1 on PbGIF1 was also confirmed by Dual-Luciferase assays.Taken together,the results showed that cytokinins control pear fruit development via the transcriptional activation of PbGIF1 by PbRR1.展开更多
This study employs similar simulation testing and discrete element simulation coupling to analyze the failure and deformation processes of a model coal seam's roof.The caving area of the overburden rock is divided...This study employs similar simulation testing and discrete element simulation coupling to analyze the failure and deformation processes of a model coal seam's roof.The caving area of the overburden rock is divided into three zones:the delamination fracture zone,broken fracture zone,and compaction zone.The caving and fracture zones'heights are approximately 110 m above the coal seam,with a maximum subsidence of 11 m.The delamination fracture zone's porosity range is between 0.2 and 0.3,while the remainder of the roof predominantly exhibits a porosity of less than 0.1.In addition,the numerical model's stress analysis revealed that the overburden rock's displacement zone forms an'arch-beam'structure starting from 160 m,with the maximum and minimum stress values decreasing as the distance of advancement increases.In the stress beam interval of the overburden rock,the maximum value changes periodically as the advancement distance increases.Based on a comparative analysis between observable data from on-site work and numerical simulation results,the stress data from the numerical simulation are essentially consistent with the actual results detected on-site,indicating the validity of the numerical simulation results.展开更多
A fundamental shift in the regional development pattern is crucial to achieving a comprehensive green transformation in China.Currently,innovation-driven green development is a significant strategic option for regiona...A fundamental shift in the regional development pattern is crucial to achieving a comprehensive green transformation in China.Currently,innovation-driven green development is a significant strategic option for regional development.As the main body of innovation and the basic unit of regional composition,enterprises have a profound impact on the development of regional economy,society,ecology,and other aspects.However,considering China’s vast territory and significant regional differences in natural environment and industrial structure,it’s necessary to further explore the specific impact paths of regional green development driven by enterprise innovation.Therefore,taking industrial enterprises as an example,based on the panel data of 30 provinces in China from 2016 to 2020,this study verifies the impact of industrial enterprise innovation on the regional green development level by constructing a parallel multiple mediating effect model and dividing the economy into eastern,central,and western regions to discuss the specific impact paths.The results show that industrial enterprise innovation has a significant positive effect on regional green development level,via different influencing paths in each region:(1)The eastern region improves the regional green development level by narrowing the urban-rural income gap;(2)The central region improves the regional green development level by reducing resource dependence;and(3)The western region raises the regional green development level by improving the rationalization of industrial structure.展开更多
The lung plays a vital role in maintaining homeostasis,as it is responsible for the exchange of oxygen and carbon dioxide.Pulmonary homeostasis is maintained by a network of tissue-resident cells,including epithelial ...The lung plays a vital role in maintaining homeostasis,as it is responsible for the exchange of oxygen and carbon dioxide.Pulmonary homeostasis is maintained by a network of tissue-resident cells,including epithelial cells,endothelial cells and leukocytes.Myeloid cells of the innate immune system and epithelial cells form a critical barrier in the lung.Recently developed unbiased next generation sequencing(NGS)has revealed cell heterogeneity in the lung with respect to physiology and pathology and has reshaped our knowledge.New phenotypes and distinct gene signatures have been identified,and these new findings enhance the diagnosis and treatment of lung diseases.Here,we present a review of the new NGS findings on myeloid cells in lung development,homeostasis,and lung diseases,including acute lung injury(ALI),lung fibrosis,chronic obstructive pulmonary disease(COPD),and lung cancer.展开更多
Instead of relying on the erroneous principles of Special Relativity, this paper proposes a new theory based on the emission of photons by a source and their re-emission by a transparent medium. Through over 60 articl...Instead of relying on the erroneous principles of Special Relativity, this paper proposes a new theory based on the emission of photons by a source and their re-emission by a transparent medium. Through over 60 articles, we have demonstrated that Special Relativity is based on optical experiments and observations that have been incorrectly explained by the theory of a non-existent ether. Our findings show that all known experiments can be explained using classical concepts of space and time, thereby refuting the theory of relativity. This article also addresses the fallacy of the widely accepted etheric Doppler effects and its significant role in the history of science.展开更多
Dear Editor,I write to present one case report of a patient suffered the panophthalmitis caused by non-metallic foreign body with no etiologic agent and recovered quickly by phacoemulsification and vitrectomy with sil...Dear Editor,I write to present one case report of a patient suffered the panophthalmitis caused by non-metallic foreign body with no etiologic agent and recovered quickly by phacoemulsification and vitrectomy with silicone oil tamponade.Ocular trauma remains a major cause of blindness, particularly in the working-age population.展开更多
Given developments in urbanization, agricultural, and technological practices, the diet and lifestyle of developed countries has changed dramatically over the course of the last century[1].
Tarq geochemical 1:100,000 Sheet is located in Isfahan province which is investigated by Iran’s Geological and Explorations Organization using stream sediment analyzes. This area has stratigraphy of Precambrian to Qu...Tarq geochemical 1:100,000 Sheet is located in Isfahan province which is investigated by Iran’s Geological and Explorations Organization using stream sediment analyzes. This area has stratigraphy of Precambrian to Quaternary rocks and is located in the Central Iran zone. According to the presence of signs of gold mineralization in this area, it is necessary to identify important mineral areas in this area. Therefore, finding information is necessary about the relationship and monitoring the elements of gold, arsenic, and antimony relative to each other in this area to determine the extent of geochemical halos and to estimate the grade. Therefore, a well-known and useful K-means method is used for monitoring the elements in the present study, this is a clustering method based on minimizing the total Euclidean distances of each sample from the center of the classes which are assigned to them. In this research, the clustering quality function and the utility rate of the sample have been used in the desired cluster (S(i)) to determine the optimum number of clusters. Finally, with regard to the cluster centers and the results, the equations were used to predict the amount of the gold element based on four parameters of arsenic and antimony grade, length and width of sampling points.展开更多
In this paper, the interaction parameters in the subregular solution model, λ1 and λ2, are regarded as a linear function of temperature, T. Therefore, the molar excess Gibbs energy of A-B binary system may be reexpr...In this paper, the interaction parameters in the subregular solution model, λ1 and λ2, are regarded as a linear function of temperature, T. Therefore, the molar excess Gibbs energy of A-B binary system may be reexpressed as follows:Gm^E=xAxB[(λ11+λ12T)+(λ21+λ22T)xB]The calculation of the model parameters, λ11, λ12, λ21and λ22, was carried out numerically from the phase diagrams for 11 alkali metal-alkali halide or alkali earth metal-halide systems. In addition, artificial neural network trained by known data has been used to predict the values of these model parameters. The predicted results are in good agreement with the .calculated ones. The applicability of the subregular solution model to the alkali metal-alkali halide or alkali earth metal-halide systems were tested by comparing the available experimental composition along the boundary of miscibility gap with the calculated ones which were obtained by using genetic algorithm. The good agreement between the calculated and experimental results across the entire liquidus is valid evidence in support of the model.展开更多
基金supported by the National Natural Science Foundation of China(82171506 and 31872778)Discipline Innovative Engineering Plan(111 Program)of China(B13036)+3 种基金Key Laboratory Grant from Hunan Province(2016TP1006)Department of Science and Technology of Hunan Province(2021DK2001,Innovative Team Program 2019RS1010)Innovation-Driven Team Project from Central South University(2020CX016)Hunan Hundred Talents Program for Young Outstanding Scientists。
文摘Proper regulation of synapse formation and elimination is critical for establishing mature neuronal circuits and maintaining brain function.Synaptic abnormalities,such as defects in the density and morphology of postsynaptic dendritic spines,underlie the pathology of various neuropsychiatric disorders.Protocadherin 17(PCDH17)is associated with major mood disorders,including bipolar disorder and depression.However,the molecular mechanisms by which PCDH17 regulates spine number,morphology,and behavior remain elusive.In this study,we found that PCDH17 functions at postsynaptic sites,restricting the number and size of dendritic spines in excitatory neurons.Selective overexpression of PCDH17 in the ventral hippocampal CA1 results in spine loss and anxiety-and depression-like behaviors in mice.Mechanistically,PCDH17 interacts with actin-relevant proteins and regulates actin filament(F-actin)organization.Specifically,PCDH17 binds to ROCK2,increasing its expression and subsequently enhancing the activity of downstream targets such as LIMK1 and the phosphorylation of cofilin serine-3(Ser3).Inhibition of ROCK2 activity with belumosudil(KD025)ameliorates the defective F-actin organization and spine structure induced by PCDH17 overexpression,suggesting that ROCK2 mediates the effects of PCDH17 on F-actin content and spine development.Hence,these findings reveal a novel mechanism by which PCDH17 regulates synapse development and behavior,providing pathological insights into the neurobiological basis of mood disorders.
基金supported by the National Key R&D Program of China,No.2019YFA0110300(to ZG)the National Natural Science Foundation of China,Nos.81773302(to YF),32070862(to ZG).
文摘Human brain development is a complex process,and animal models often have significant limitations.To address this,researchers have developed pluripotent stem cell-derived three-dimensional structures,known as brain-like organoids,to more accurately model early human brain development and disease.To enable more consistent and intuitive reproduction of early brain development,in this study,we incorporated forebrain organoid culture technology into the traditional unguided method of brain organoid culture.This involved embedding organoids in matrigel for only 7 days during the rapid expansion phase of the neural epithelium and then removing them from the matrigel for further cultivation,resulting in a new type of human brain organoid system.This cerebral organoid system replicated the temporospatial characteristics of early human brain development,including neuroepithelium derivation,neural progenitor cell production and maintenance,neuron differentiation and migration,and cortical layer patterning and formation,providing more consistent and reproducible organoids for developmental modeling and toxicology testing.As a proof of concept,we applied the heavy metal cadmium to this newly improved organoid system to test whether it could be used to evaluate the neurotoxicity of environmental toxins.Brain organoids exposed to cadmium for 7 or 14 days manifested severe damage and abnormalities in their neurodevelopmental patterns,including bursts of cortical cell death and premature differentiation.Cadmium exposure caused progressive depletion of neural progenitor cells and loss of organoid integrity,accompanied by compensatory cell proliferation at ectopic locations.The convenience,flexibility,and controllability of this newly developed organoid platform make it a powerful and affordable alternative to animal models for use in neurodevelopmental,neurological,and neurotoxicological studies.
基金Supported by the National Natural Science Foundation of China,No.82273457the Natural Science Foundation of Guangdong Province,No.2023A1515012762 and No.2021A1515010846+1 种基金Special Grant for Key Area Programs of Guangdong Department of Education,No.2021ZDZX2040Science and Technology Special Project of Guangdong Province,No.210715216902829.
文摘The sine oculis homeobox homolog(SIX)family,a group of transcription factors characterized by a conserved DNA-binding homology domain,plays a critical role in orchestrating embryonic development and organogenesis across various organisms,including humans.Comprising six distinct members,from SIX1 to SIX6,each member contributes uniquely to the development and differentiation of diverse tissues and organs,underscoring the versatility of the SIX family.Dysregulation or mutations in SIX genes have been implicated in a spectrum of developmental disorders,as well as in tumor initiation and progression,highlighting their pivotal role in maintaining normal developmental trajectories and cellular functions.Efforts to target the transcriptional complex of the SIX gene family have emerged as a promising strategy to inhibit tumor development.While the development of inhibitors targeting this gene family is still in its early stages,the significant potential of such interventions holds promise for future therapeutic advances.Therefore,this review aimed to comprehensively explore the advancements in understanding the SIX family within gastrointestinal cancers,focusing on its critical role in normal organ development and its implications in gastrointestinal cancers,including gastric,pancreatic,colorectal cancer,and hepatocellular carcinomas.In conclusion,this review deepened the understanding of the functional roles of the SIX family and explored the potential of utilizing this gene family for the diagnosis,prognosis,and treatment of gastrointestinal cancers.
基金supported by the National Natural Science Foundation of China,Nos.81901156(to ZZ),82271200(to ZZ),82171308(to XC)the Fundamental Research Funds for the Central Universities,No.xzy012022035(to ZZ)+1 种基金the Natural Science Foundation of Shaanxi Province,Nos.2021JM-261(to QK),2023-YBSF-303(to ZZ)Traditional Chinese Medicine Project of Shaanxi Province,No.2019-ZZ-JC047(to QK)。
文摘The organotypic retinal explant culture has been established for more than a decade and offers a range of unique advantages compared with in vivo experiments and cell cultures.However,the lack of systematic and continuous comparison between in vivo retinal development and the organotypic retinal explant culture makes this model controversial in postnatal retinal development studies.Thus,we aimed to verify the feasibility of using this model for postnatal retinal development studies by comparing it with the in vivo retina.In this study,we showed that postnatal retinal explants undergo normal development,and exhibit a consistent structure and timeline with retinas in vivo.Initially,we used SOX2 and PAX6 immunostaining to identify retinal progenitor cells.We then examined cell proliferation and migration by immunostaining with Ki-67 and doublecortin,respectively.Ki-67-and doublecortin-positive cells decreased in both in vivo and explants during postnatal retinogenesis,and exhibited a high degree of similarity in abundance and distribution between groups.Additionally,we used Ceh-10 homeodomain-containing homolog,glutamate-ammonia ligase(glutamine synthetase),neuronal nuclei,and ionized calcium-binding adapter molecule 1 immunostaining to examine the emergence of bipolar cells,Müller glia,mature neurons,and microglia,respectively.The timing and spatial patterns of the emergence of these cell types were remarkably consistent between in vivo and explant retinas.Our study showed that the organotypic retinal explant culture model had a high degree of consistency with the progression of in vivo early postnatal retina development.The findings confirm the accuracy and credibility of this model and support its use for long-term,systematic,and continuous observation.
文摘The critical role of patient-reported outcome measures(PROMs)in enhancing clinical decision-making and promoting patient-centered care has gained a profound significance in scientific research.PROMs encapsulate a patient's health status directly from their perspective,encompassing various domains such as symptom severity,functional status,and overall quality of life.By integrating PROMs into routine clinical practice and research,healthcare providers can achieve a more nuanced understanding of patient experiences and tailor treatments accordingly.The deployment of PROMs supports dynamic patient-provider interactions,fostering better patient engagement and adherence to tre-atment plans.Moreover,PROMs are pivotal in clinical settings for monitoring disease progression and treatment efficacy,particularly in chronic and mental health conditions.However,challenges in implementing PROMs include data collection and management,integration into existing health systems,and acceptance by patients and providers.Overcoming these barriers necessitates technological advancements,policy development,and continuous education to enhance the acceptability and effectiveness of PROMs.The paper concludes with recommendations for future research and policy-making aimed at optimizing the use and impact of PROMs across healthcare settings.
基金supported by the National Natural Science Foundation of China(81770514)the 2020 Scientist Plus Engineer Program of Shaanxi Province,China(K4050422468)+2 种基金the Key Research&Development Plan of Shaanxi Province,China(2020NY-002)the Natural Science Basis Research Plan of Shaanxi Province,China(2023-JC-QN-0242)the China Agriculture Research System of MOF and MARA(CARS-37)。
文摘Testicular development is an important biological process in male and requires interaction between the male germ cells and somatic cells.However,the mechanisms of testicular development in livestock,particularly in cattle,are poorly understood.Furthermore,cellular heterogeneity hinders the profiling of different cell types at different developmental stages.In this study,we first performed a single-cell transcriptomic study of the bovine testis development during puberty by using 10×genomics single-cell RNA sequencing(scRNA-seq).By collecting the scRNA-seq data from 11,083 cells from prepubertal and pubertal bovine testes,a high-resolution scRNA-seq atlas was described,identifying 9 somatic and 13 spermatogenic clusters.We also distinguished several stage-specific marker genes for bovine germ cells and somatic cells,such as GRAF2 and MORC1 for SSC(spermatogonial stem cells),HJURP and TCF19 for differentiating spermatogonia,ARSE for immature Sertoli,CLEC12B for mature Sertoli,LOC112441470 for Leydig.In conclusion,we have examined the transcription levels and constructed the single-cell developmental maps of germ cells and somatic cells during testicular development in Angus cattle.The datasets provided new insights into spermatogenesis and testicular somatic cell development in cattle.
基金supported by grants from the Laboratory of Lingnan Modern Agriculture Project (Grant No.NZ NT2021004)China Litchi and Longan Industry Technology Research System (Grant No.CARS-32-07)。
文摘Litchi (Litchi chinensis Sonn.) is a well-known tropical and subtropical woody fruit that originated from southern China (Wei et al.,2017;Hu et al.,2022).Based on the development of the embryo,litchi varieties can be divided into three distinct groups:large-seeded cultivars,small (abortive)-seeded cultivars and partial abortive-seeded cultivars.Seedless or the reduction in seed size due to embryo abortion is a desirable trait in fruit trees as it directly influences the texture and economic value of fleshy fruits,making small (abortive)-seeded litchi cultivars the most preferred.However,in current production practices,there is no efficient method available to induce or promote high seed abortion in litchi fruit.Therefore,understanding the stenospermy mechanisms of litchi seed development is of great significance for improving agricultural practices and managing genetic resources.
基金supported by the National Natural Science Foundation of China(32001491,32360493)Natural Science Foundation of Sichuan Province(2022NSFSC0153,2022NSFSC1754,2023NSFSC1170)the Key Research and Development Program of Sichuan Province(2021YFYZ0016).
文摘The enzyme C-14 sterol reductase is involved in biosynthesis of brassinosteroids(BR)and sterols,as well as plant development.OsFK1,a member of the sterol biosynthesis pathway located in the endoplasmic reticulum(ER),encodes C-14 sterol reductase.However,there is little research on the function of C-14 sterol reductase in rice.Compared with the wild type,an osfk1 mutant showed dwarf phenotype and premature aging in the second leaf during the trefoil stage,and abnormal development of leaf veins during the tillering stage.The osfk1 mutant showed signs of aberrant PCD,as evidenced by TUNEL staining.This suggested that high ROS buildup caused DNA damage and ROS-mediated cell death in the mutant.The osfk1 mutant also showed decreased chlorophyll content and aberrant chloroplast structure.Sequencing of the osfk1 mutant allele revealed a non-synonymous G to A mutation in the final intron,leading to early termination.Here,we identified the OsFK1 allele,cloned it by Mutmap sequencing,and verified it by complementation.HPLC-MS/MS assays demonstrated that the osfk1 mutation caused lower phytosterol levels.These findings showed that the OsFK1 allele encoding C-14 sterol reductase is involved in phytosterol biosynthesis and mediates normal development of rice plants.
文摘Climate change is an alarming global challenge, particularly affecting the least developed countries (LDCs) including Liberia. These countries, located in regions prone to unpredictable temperature and precipitation changes, are facing significant challenges, particularly in climate-sensitive sectors such as mining and agriculture. LDCs need more resilience to adverse climate shocks but have limited capacity for adaptation compared to other developed and developing nations. This paper examines Liberia’s susceptibility to climate change as a least developed country, focusing on its exposure, sensitivity, and adaptive capacity. It provides an overview of LDCs and outlines the global distribution of carbon dioxide emissions. The paper also evaluates specific challenges that amplify Liberia’s vulnerability and constrain sustainable adaptation, providing insight into climate change’s existing and potential effects. The paper emphasizes the urgency of addressing climate impacts on Liberia and calls for concerted local and international efforts for effective and sustainable mitigation efforts. It provides recommendations for policy decisions and calls for further research on climate change mitigation and adaptation.
基金supported by the National Natural Science Foundation of China(Grant No.42174118)a research grant(Grant No.ZDJ 2020-7)from the National Institute of Natural Hazards,Ministry of Emergency Management of China.
文摘The hydraulic testing of pre-existing fractures(HTPF)is one of the most promising in situ stress measurement methods,particularly for three-dimensional stress tensor determination.However,the stress tensor determination based on the HTPF method requires at least six tests or a minimum of 14-15 tests(under different conditions)for reliable results.In this study,we modified the HTPF method by considering the shear stress on each pre-existing fracture,which increased the number of equations for the stress tensor determination and decreased the number of tests required.Different shear stresses were attributed to different fractures by random sampling;therefore,the stress tensors were obtained by searching for the optimal solution using the least squares criterion based on the Monte Carlo method.Thereafter,we constrained the stress tensor based on the tensile strength criterion,compressive strength criterion,and vertical stress constraints.The inverted stress tensors were presented and analyzed based on the tensorial nature of the stress using the Euclidean mean stress tensor.Two stress-measurement campaigns in Weifang(Shandong Province,China)and Mercantour road tunnel(France)were implemented to highlight the validity and efficiency of the modified HTPF(M-HTPF)method.The results showed that the M-HTPF method can be applied for stress tensor inversion using only three to four tests on pre-existing fractures,neglecting the stress gradient.The inversion results were confined to relatively small distribution dispersions and were significantly reliable and stable due to the shear stresses on the fractures and the stress constraints employed.The M-HTPF method is highly feasible and efficient for complete stress tensor determination in a single borehole.
基金supported by the China Agriculture Research System of MOF and MARA。
文摘As a cell proliferation regulator involved in wide biological processes in plants,GRF-INTERACTING FACTOR(GIF)controls different tissues development.However,whether GIF participates in fruit development remains unclear.According to transcriptome data,we identified PbGIF1was highly expressed during fruit development in cytokinins induced parthenocarpy pear.In the present study,the biofunction of PbGIF1 was initially verified.Overexpression of PbGIF1 promoted fruit size of transgenic tomato.The size of flesh fruit was not affected by cell expansion but the cell proliferation was promoted by overexpressing Pb GIF1.The accelerated cell proliferation process was also observed in PbGIF1-overexpressed transgenic pear fruit calli.The transcriptional regulation of cytokinins on PbGIF1 was further confirmed by exogenous CPPU treatments in pear fruitlets.To investigate the underlying mechanism,the cytokinins-responded factor,PbRR1,was further focused on.The results of Yeast-one-hybrid assay suggested that PbRR1 can bind to the promoter sequence of PbGIF1.The transcriptional activation of PbRR1 on PbGIF1 was also confirmed by Dual-Luciferase assays.Taken together,the results showed that cytokinins control pear fruit development via the transcriptional activation of PbGIF1 by PbRR1.
基金National Key R&D Program of China(2023YFC3009100,2023YFC3009102)National Natural Science Foundation of China(52304198)Open Fund of the National and Local Joint Engineering Research Center for Safe and Accurate Coal Mining(EC2021016).
文摘This study employs similar simulation testing and discrete element simulation coupling to analyze the failure and deformation processes of a model coal seam's roof.The caving area of the overburden rock is divided into three zones:the delamination fracture zone,broken fracture zone,and compaction zone.The caving and fracture zones'heights are approximately 110 m above the coal seam,with a maximum subsidence of 11 m.The delamination fracture zone's porosity range is between 0.2 and 0.3,while the remainder of the roof predominantly exhibits a porosity of less than 0.1.In addition,the numerical model's stress analysis revealed that the overburden rock's displacement zone forms an'arch-beam'structure starting from 160 m,with the maximum and minimum stress values decreasing as the distance of advancement increases.In the stress beam interval of the overburden rock,the maximum value changes periodically as the advancement distance increases.Based on a comparative analysis between observable data from on-site work and numerical simulation results,the stress data from the numerical simulation are essentially consistent with the actual results detected on-site,indicating the validity of the numerical simulation results.
基金supported by the“Second Tibetan Plateau Scientific Expedition and Research Program(STEP),Grant No.2019QZKK1007”from the Ministry of Science and Technology of China。
文摘A fundamental shift in the regional development pattern is crucial to achieving a comprehensive green transformation in China.Currently,innovation-driven green development is a significant strategic option for regional development.As the main body of innovation and the basic unit of regional composition,enterprises have a profound impact on the development of regional economy,society,ecology,and other aspects.However,considering China’s vast territory and significant regional differences in natural environment and industrial structure,it’s necessary to further explore the specific impact paths of regional green development driven by enterprise innovation.Therefore,taking industrial enterprises as an example,based on the panel data of 30 provinces in China from 2016 to 2020,this study verifies the impact of industrial enterprise innovation on the regional green development level by constructing a parallel multiple mediating effect model and dividing the economy into eastern,central,and western regions to discuss the specific impact paths.The results show that industrial enterprise innovation has a significant positive effect on regional green development level,via different influencing paths in each region:(1)The eastern region improves the regional green development level by narrowing the urban-rural income gap;(2)The central region improves the regional green development level by reducing resource dependence;and(3)The western region raises the regional green development level by improving the rationalization of industrial structure.
基金the USA National Institutes of Health Grant R01-HL-079669(J.F.)USA National Institutes of Health Grant R01HL076179(J.F.)+2 种基金USA National Institutes of Health Grant R01HL-139547(J.F.)VA Merit Award 1I01BX002729(J.F.)VA BLR&D Award 1IK6BX004211(J.F.).
文摘The lung plays a vital role in maintaining homeostasis,as it is responsible for the exchange of oxygen and carbon dioxide.Pulmonary homeostasis is maintained by a network of tissue-resident cells,including epithelial cells,endothelial cells and leukocytes.Myeloid cells of the innate immune system and epithelial cells form a critical barrier in the lung.Recently developed unbiased next generation sequencing(NGS)has revealed cell heterogeneity in the lung with respect to physiology and pathology and has reshaped our knowledge.New phenotypes and distinct gene signatures have been identified,and these new findings enhance the diagnosis and treatment of lung diseases.Here,we present a review of the new NGS findings on myeloid cells in lung development,homeostasis,and lung diseases,including acute lung injury(ALI),lung fibrosis,chronic obstructive pulmonary disease(COPD),and lung cancer.
文摘Instead of relying on the erroneous principles of Special Relativity, this paper proposes a new theory based on the emission of photons by a source and their re-emission by a transparent medium. Through over 60 articles, we have demonstrated that Special Relativity is based on optical experiments and observations that have been incorrectly explained by the theory of a non-existent ether. Our findings show that all known experiments can be explained using classical concepts of space and time, thereby refuting the theory of relativity. This article also addresses the fallacy of the widely accepted etheric Doppler effects and its significant role in the history of science.
基金Supported by Natural Science Foundation of China (No.81571819 No.81500766)the Natural Science Foundation of Zhejiang Province, China (No.LY14H120004)
文摘Dear Editor,I write to present one case report of a patient suffered the panophthalmitis caused by non-metallic foreign body with no etiologic agent and recovered quickly by phacoemulsification and vitrectomy with silicone oil tamponade.Ocular trauma remains a major cause of blindness, particularly in the working-age population.
文摘Given developments in urbanization, agricultural, and technological practices, the diet and lifestyle of developed countries has changed dramatically over the course of the last century[1].
文摘Tarq geochemical 1:100,000 Sheet is located in Isfahan province which is investigated by Iran’s Geological and Explorations Organization using stream sediment analyzes. This area has stratigraphy of Precambrian to Quaternary rocks and is located in the Central Iran zone. According to the presence of signs of gold mineralization in this area, it is necessary to identify important mineral areas in this area. Therefore, finding information is necessary about the relationship and monitoring the elements of gold, arsenic, and antimony relative to each other in this area to determine the extent of geochemical halos and to estimate the grade. Therefore, a well-known and useful K-means method is used for monitoring the elements in the present study, this is a clustering method based on minimizing the total Euclidean distances of each sample from the center of the classes which are assigned to them. In this research, the clustering quality function and the utility rate of the sample have been used in the desired cluster (S(i)) to determine the optimum number of clusters. Finally, with regard to the cluster centers and the results, the equations were used to predict the amount of the gold element based on four parameters of arsenic and antimony grade, length and width of sampling points.
文摘In this paper, the interaction parameters in the subregular solution model, λ1 and λ2, are regarded as a linear function of temperature, T. Therefore, the molar excess Gibbs energy of A-B binary system may be reexpressed as follows:Gm^E=xAxB[(λ11+λ12T)+(λ21+λ22T)xB]The calculation of the model parameters, λ11, λ12, λ21and λ22, was carried out numerically from the phase diagrams for 11 alkali metal-alkali halide or alkali earth metal-halide systems. In addition, artificial neural network trained by known data has been used to predict the values of these model parameters. The predicted results are in good agreement with the .calculated ones. The applicability of the subregular solution model to the alkali metal-alkali halide or alkali earth metal-halide systems were tested by comparing the available experimental composition along the boundary of miscibility gap with the calculated ones which were obtained by using genetic algorithm. The good agreement between the calculated and experimental results across the entire liquidus is valid evidence in support of the model.