In the words of the late Sir Colin Blakemore,neurologists have historically sought to infer brain functions in a manner akin to to king a hammer to a computeranalyzing localized anatomical lesions caused by trauma,tum...In the words of the late Sir Colin Blakemore,neurologists have historically sought to infer brain functions in a manner akin to to king a hammer to a computeranalyzing localized anatomical lesions caused by trauma,tumors,or strokes,noting deficits,and inferring what functions certain brain regions may be responsible for.This approach exemplifies a deletion heuristic,where the absence of a specific function reveals insights about the underlying structures or mechanisms responsible for it.By observing what is lost when a particular brain region is damaged,throughout the history of the field,neurologists have pieced together the intricate relationship between anatomy and function.展开更多
Glaucoma is a group of diseases characterized by progressive optic nerve degeneration,with the characteristic pathological change being death of retinal ganglion cells(RGCs),which ultimately causes visual field loss a...Glaucoma is a group of diseases characterized by progressive optic nerve degeneration,with the characteristic pathological change being death of retinal ganglion cells(RGCs),which ultimately causes visual field loss and irreversible blindness.Elevated intraocular pressure(IOP)remains the most important risk factor for glaucoma,but the exact mechanism responsible for the death of RGCs is currently unknown.Neurotrophic factor deficiency,impaired mitochondrial structure and function,disrupted axonal transport,disturbed Ca2+homeostasis,and activation of apoptotic and autophagic pathways play important roles in RGC death in glaucoma.This review was conducted using Web of Science,PubMed,Project,and other databases to summarize the relevant mechanisms of death of RGCs in glaucoma,in addition to outlining protective treatments to improve the degradation of RGCs.展开更多
The original online version of this article was revised:In this article the caption to Fig 14 was inadvertently swapped.The space should be added after")"and the letter"f)"at the end should be dele...The original online version of this article was revised:In this article the caption to Fig 14 was inadvertently swapped.The space should be added after")"and the letter"f)"at the end should be deleted.In this article the wrong figure appeared as Fig.15;the figure should have appeared as shown below.展开更多
Dear Editor,X-linked retinoschisis(XLRS)is a rare X-linked recessive disorder predominantly afflicting young males.The schisis of the retinal layers is a result of deleterious mutations in the RS1 gene.Insufficient ep...Dear Editor,X-linked retinoschisis(XLRS)is a rare X-linked recessive disorder predominantly afflicting young males.The schisis of the retinal layers is a result of deleterious mutations in the RS1 gene.Insufficient epidemiological data has caused significant variation in reported global prevalence,with estimates fluctuating between 1 in 5000 and 1 in 30000 individuals[1].A large follow-up multicenter study recently published has yielded noteworthy findings concerning the phenotypic spectrum,long-term natural history,and genotype of XLRS.The investigation revealed a significant variability in visual function and disease progression,with particular variants of the RS1 gene displaying diverse phenotypic expressions,suggesting the intricate genetic basis underlying this disorder[2].The range of visual impairments associated with XLRS is extensive,varying from minor to severe.This condition is also characterized by specific retinal abnormalities,including radial streaks emanating from a divided central fovea,schisis affecting the inner layers of the retina in peripheral areas,and a diminished amplitude ratio of b-to a-wave,or even an electronegative electroretinography(ERG)[3].At their initial consultation,the majority of individuals with XLRS exhibit visual acuity(VA)levels between 20/60 and 20/120.However,there is a significant diversity in the condition’s presentation and progression,even among relatives,with VA levels spanning from near-normal to complete loss of sight[4-5].While vision tends to be reasonably consistent over several years for those with XLRS,there is documentation of a more rapid decline in later adulthood,specifically during the fourth and fifth decades,due to central retinal degeneration[5-7].Moreover,those with XLRS face an elevated risk for serious visual issues,such as retinal detachment,vitreous hemorrhages,and neovascular glaucoma[4].Female carriers could be found with slightly abnormal retinal changes without clinical symptoms[5].Even within the same family,the manifestation and progression of the condition can vary greatly,with individuals experiencing anything from nearly normal vision to complete loss of sight[8-9].Earlier investigations have revealed that retinoschisisrelated cystoid degeneration can impact multiple layers of the retina,beginning at the retinal nerve fiber zone and continuing to the nuclear stratum,with considerable fluctuation in the severity of the schisis[10-13].展开更多
BACKGROUND Acute myeloid leukemia(AML)is a complicated disease with uncontrolled hematopoietic precursor proliferation induced by various genetic alterations.Runt-related transcription factor-1(RUNX1)is commonly disru...BACKGROUND Acute myeloid leukemia(AML)is a complicated disease with uncontrolled hematopoietic precursor proliferation induced by various genetic alterations.Runt-related transcription factor-1(RUNX1)is commonly disrupted by chromosomal translocations in hematological malignancies.AIM To characterize RUNX1 gene rearrangements and copy number variations in newly diagnosed adult AML patients,with an emphasis on the impact of clinical and laboratory features on the outcome.METHODS Fluorescence in situ hybridization was used to test RUNX1 gene alterations in 77 newly diagnosed adult AML cases.NPM1,FLT3/ITD,FLT3/TKD,and KIT mutations were tested by PCR.Prognostic clinical and laboratory findings were studied in relation to RUNX1 alterations.RESULTS RUNX1 abnormalities were detected by fluorescence in situ hybridization in 41.6%of patients:20.8%had translocations,22.1%had amplification,and 5.2%had deletion.Translocations prevailed in AML-M2(P=0.019)with a positive expression of myeloperoxidase(P=0.031),whereas deletions dominated in M4 and M5 subtypes(P=0.008)with a positive association with CD64 expression(P=0.05).The modal chromosomal number was higher in cases having amplifications(P=0.007)and lower in those with deletions(P=0.008).RUNX1 abnormalities were associated with complex karyotypes(P<0.001)and were mutually exclusive of NPM1 mutations.After 44 months of follow-up,RUNX1 abnormalities affected neither patients’response to treatment nor overall survival.CONCLUSION RUNX1 abnormalities were mutually exclusive of NPM1 mutations.RUNX1 abnormalities affected neither patients’response to treatment nor overall survival.展开更多
BACKGROUND Each year,more than a million people are diagnosed with gastric cancer(GC)worldwide,and the incidence of this disease is projected to increase.Helicobacter pylori(H.pylori)is the major cause of GC.Managing ...BACKGROUND Each year,more than a million people are diagnosed with gastric cancer(GC)worldwide,and the incidence of this disease is projected to increase.Helicobacter pylori(H.pylori)is the major cause of GC.Managing infections caused by H.pylori and investigating their contribution to GC carcinogenesis are crucial for advancing diagnosis and treatment.Deleted in malignant brain tumors 1(DMBT1)is associated with the development of H.pylori and GC.However,the precise underlying mechanism is unclear.AIM To explore the role of DMBT1,as modulated by H.pylori,in the development,proliferation,and metastasis of GC.METHODS Utilizing human GC cells,DMBT1 gene silencing,and H.pylori treatment,four cell groups(control,H.pylori,si-DMBT1,and H.pylori+si-DMBT1)were subjected to cell counting kit-8,scratch,and Transwell assays.The DMBT1 expression was assessed by quantitative real-time polymerase chain reaction and Western blot.RESULTS In cellular tests,H.pylori+si-DMBT1 showed the greatest ability to proliferate,migration,and invasion capabilities,followed by the si-DMBT1,H.pylori,and control groups.DMBT1 mRNA was found to be the highest in control group,next in si-DMBT1,H.pylori and H.pylori+si-DMBT1,while H.pylori+si-DMBT1 showed the least expression.The results the Western blot assay showed a consistent trend of decreasing DMBT1 protein and mRNA levels.CONCLUSION Through inhibition of DMBT1,H.pylori could enhance GC’s proliferation,metastasis and invasion.Our findings revealed a novel connection between H.pylori infection,inflammation,and GC.展开更多
Genome rearrangement is an important process that leads to genetic diversity,including mutation-related insertions,deletions,or inversions in the genome[1,2].
BACKGROUND Rett syndrome is a monogenic X-linked dominant condition that affects 1/(10000-15000)girls due to de novo mutations in the methyl-CpG binding protein 2(MECP2)gene mapped to chromosome Xq28.The disease-causi...BACKGROUND Rett syndrome is a monogenic X-linked dominant condition that affects 1/(10000-15000)girls due to de novo mutations in the methyl-CpG binding protein 2(MECP2)gene mapped to chromosome Xq28.The disease-causing gene was identified as a mutation in the MECP2 gene,which is found in approximately 80%of patients diagnosed with Rett syndrome.Although chromosomal changes resulting in del(15)(q11q13)are usually associated with Angelman and Prader-Willi syndrome,very few cases,if any,of Rett syndrome with terminal 15q22-qter deletion have been published in English literature.CASE SUMMARY In this study,we report an unusual and rare clinical presentation of Rett syndrome in a 12-year-old Sudanese girl.The patient was brought in by her parents,complaining of gradual onset of abnormal walking,abnormal hand movement,loss of speech,and mental retardation for ten years.There was no reported history of convulsions or loss of consciousness.Clinical examination revealed microcephaly with no other apparent dysmorphic features,intact cranial nerves,and abnormal gait.She showed repetitive and stereotyped behaviors,including hand flapping,stimming,and chest pounding,which were concomitant with autism spectrum disorder.Magnetic resonance imaging and electroencephalography investigations were normal,and cytogenetic analysis showed 46,XX,del(15)(q22qter).Further molecular analysis using whole sequencing of MECP2 revealed an alteration cytosine>thymine at nucleotide 401,leading to phenylalanine replacing a serine at amino acid position 134.CONCLUSION This case,the first reported instance of Rett syndrome in Sudan,is of significant interest.The patient carries both the MECP2 gene mutation and the chromosome 15q22-qter deletion,which may explain the autistic behavior with atypical presentation of Rett syndrome.This report expands the genetic diversity of Rett syndrome,demonstrating how co-occurring 15q22-qter deletions can reshape MECP2-associated phenotypes in Rett syndrome.展开更多
The female inflorescence,or ear,of maize develops no branch meristem(BM),which differs from the male inforescence,or tassel.While the mutations of some well documented genes,such as fea2/3/4 and ramosa1/2/3,can cause ...The female inflorescence,or ear,of maize develops no branch meristem(BM),which differs from the male inforescence,or tassel.While the mutations of some well documented genes,such as fea2/3/4 and ramosa1/2/3,can cause the branched architecture of ears in maize,such mutations also change the normal phenotypic performance of the tassels.In the present study,a natural maize mutant with branched ears,named branched ear1(be1),was characterized.be1 shows several branched ears at the base of the central ear with unchanged architecture of the tassels.Besides,both the branched and central ears of be1 possess regularly arranged kerels.The phenotypic characteristics of be1 differ completely from those reported mutants of fasciated ears or RAMOSA-like ears in maize.An SEM survey at the very early development stage showed that meristems with three protrusions,similar to the BM in tassels,were present during the development of the branched ears in be1.Gene mapping and sequence alignment suggested that TEOSINTE BRANCHED1(TB1)was the candidate gene of BE1.Further verification showed that a be1-specific 31 bp deletion at the downstream of BE1 led to statistically reduced expression of this gene in the immature ear,which serves as the potential causal reason for the branched ears of be1.CRISPR/Cas9-based gene editing downstream of TB1 complemented the phenotypic architecture of branched ears,suggesting that TB1 was the target of BE1,and it was named as Zm TB1be1.The results of the present study implied a novel function of TB1 in female inforescence development,rather than shaping the plant architecture in maize.Meanwhile,further functional dissection of ZmTB1be1might shed new light on TB1,the most famous domestication related gene in maize.展开更多
Long noncoding RNA and microRNA are regulatory noncoding RNAs that are implicated in Alzheimer's disease, but the role of long noncoding RNA-associated competitive endogenous RNA has not been fully elucidated. The...Long noncoding RNA and microRNA are regulatory noncoding RNAs that are implicated in Alzheimer's disease, but the role of long noncoding RNA-associated competitive endogenous RNA has not been fully elucidated. The long noncoding RNA growth arrest-specific 5(GAS5) is a member of the 5′-terminal oligopyrimidine gene family that may be involved in neurological disorders, but its role in Alzheimer's disease remains unclear. This study aimed to investigate the function of GAS5 and construct a GAS5-associated competitive endogenous RNA network comprising potential targets. RNA sequencing results showed that GAS5 was upregulated in five familial Alzheimer's disease(5×FAD) mice, APPswe/PSEN1dE9(APP/PS1) mice, Alzheimer's disease-related APPswe cells, and serum from patients with Alzheimer's disease. Functional experiments with targeted overexpression and silencing demonstrated that GAS5 played a role in cognitive dysfunction and multiple Alzheimer's disease-associated pathologies, including tau hyperphosphorylation, amyloid-beta accumulation, and neuronal apoptosis. Mechanistic studies indicated that GAS5 acted as an endogenous sponge by competing for microRNA-23b-3p(miR-23b-3p) binding to regulate its targets glycogen synthase kinase 3beta(GSK-3β) and phosphatase and tensin homologue deleted on chromosome 10(PTEN) expression in an Argonaute 2-induced RNA silencing complex(RISC)-dependent manner. GAS5 inhibited miR-23b-3p-mediated GSK-3β and PTEN cascades with a feedforward PTEN/protein kinase B(Akt)/GSK-3β linkage. Furthermore, recovery of GAS5/miR-23b-3p/GSK-3β/PTEN pathways relieved Alzheimer's disease-like symptoms in vivo, indicated by the amelioration of spatial cognition, neuronal degeneration, amyloid-beta load, and tau phosphorylation. Together, these findings suggest that GAS5 promotes Alzheimer's disease pathogenesis. This study establishes the functional convergence of the GAS5/miR-23b-3p/GSK-3β/PTEN pathway on multiple pathologies, suggesting a candidate therapeutic target in Alzheimer's disease.展开更多
Autism spectrum disorders are a group of neurodevelopmental disorders involving more than 1100 genes,including Ctnnd2 as a candidate gene.Ctnnd2knockout mice,serving as an animal model of autis m,have been demonstrate...Autism spectrum disorders are a group of neurodevelopmental disorders involving more than 1100 genes,including Ctnnd2 as a candidate gene.Ctnnd2knockout mice,serving as an animal model of autis m,have been demonstrated to exhibit decreased density of dendritic spines.The role of melatonin,as a neuro hormone capable of effectively alleviating social interaction deficits and regulating the development of dendritic spines,in Ctnnd2 deletion-induced nerve injury remains unclea r.In the present study,we discove red that the deletion of exon 2 of the Ctnnd2 gene was linked to social interaction deficits,spine loss,impaired inhibitory neurons,and suppressed phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt) signal pathway in the prefrontal cortex.Our findings demonstrated that the long-term oral administration of melatonin for 28 days effectively alleviated the aforementioned abnormalities in Ctnnd2 gene-knockout mice.Furthermore,the administration of melatonin in the prefro ntal cortex was found to improve synaptic function and activate the PI3K/Akt signal pathway in this region.The pharmacological blockade of the PI3K/Akt signal pathway with a PI3K/Akt inhibitor,wo rtmannin,and melatonin receptor antagonists,luzindole and 4-phenyl-2-propionamidotetralin,prevented the melatonin-induced enhancement of GABAergic synaptic function.These findings suggest that melatonin treatment can ameliorate GABAe rgic synaptic function by activating the PI3K/Akt signal pathway,which may contribute to the improvement of dendritic spine abnormalities in autism spectrum disorders.展开更多
BACKGROUND The modified Xiaoyao San(MXS)formula is an adjuvant drug recommended by the National Health Commission of China for the treatment of liver cancer,which has the effect of preventing postoperative recurrence ...BACKGROUND The modified Xiaoyao San(MXS)formula is an adjuvant drug recommended by the National Health Commission of China for the treatment of liver cancer,which has the effect of preventing postoperative recurrence and metastasis of hepatocellular carcinoma and prolonging patient survival.However,the molecular mechanisms underlying that remain unclear.AIM To investigate the role and mechanisms of MXS in ameliorating hepatic injury,steatosis and inflammation.METHODS A choline-deficient/high-fat diet-induced rat nonalcoholic steatohepatitis(NASH)model was used to examine the effects of MXS on lipid accumulation in primary hepatocytes.Liver tissues were collected for western blotting and immunohisto chemistry(IHC)assays.Lipid accumulation and hepatic fibrosis were detected using oil red staining and Sirius red staining.The serum samples were collected for biochemical assays and NMR-based metabonomics analysis.The inflammation/lipid metabolism-related signaling and regulators in liver tissues were also detected to reveal the molecular mechanisms of MXS against NASH.RESULTS MXS showed a significant decrease in lipid accumulation and inflammatory response in hepatocytes under metabolic stress.The western blotting and IHC results indicated that MXS activated AMPK pathway but inhibited the expression of key regulators related to lipid accumulation,inflammation and hepatic fibrosis in the pathogenesis of NASH.The metabonomics analysis systemically indicated that the arachidonic acid metabolism and steroid hormone synthesis are the two main target metabolic pathways for MXS to ameliorate liver inflammation and hepatic steatosis.Mechanistically,we found that MXS protected against NASH by attenuating the sex hormone-related metabolism,especially the metabolism of male hormones.CONCLUSION MXS ameliorates inflammation and hepatic steatosis of NASH by inhibiting the metabolism of male hormones.Targeting male hormone related metabolic pathways may be the potential therapeutic approach for NASH.展开更多
Erratum to:Rare Met.(2014)1:1-15 D0I10.1007/s12598-013-0217-8 Due to the negligence of the first author,the address for the corresponding author in the final proof version was duplicate with wrong one.Apologize for th...Erratum to:Rare Met.(2014)1:1-15 D0I10.1007/s12598-013-0217-8 Due to the negligence of the first author,the address for the corresponding author in the final proof version was duplicate with wrong one.Apologize for this error and the following address should be deleted:R.-M.Wang,Institute of Metal Research,Chinese Academy of Sciences,Shenyang 110016,China.展开更多
Background: DiGeorge syndrome (also known as velo-cardio-facial syndrome) is a rare multisystem genetic disorder occurring in approximately 1 in 4000 to 1 in 6000 live births [1]. Although advances in genetic screenin...Background: DiGeorge syndrome (also known as velo-cardio-facial syndrome) is a rare multisystem genetic disorder occurring in approximately 1 in 4000 to 1 in 6000 live births [1]. Although advances in genetic screening have improved diagnosis in developed countries, the condition remains underdiagnosed in developing nations such as the Republic of Moldova, where access to genetic testing and family planning services is limited. Routine prenatal screening usually includes regular ultrasounds, monitoring of blood pressure, complete blood counts, coagulation studies, glucose, urine protein, and urine culture. Current ultrasound techniques have limitations in detecting this syndrome due to variability in interpretation, and genetic testing is often performed based on clinical discretion. The ultrasound could potentially point towards a genetic problem, as in DiGeorge, if multiple cardiac malformations are spotted in utero, but most cases such as this one are diagnosed after birth while being described as totally normal on prenatal ultrasound. Purpose: This study aims to highlight the diagnostic challenges and the need for comprehensive evaluation in identifying DiGeorge syndrome, emphasizing the importance of considering the syndrome as a whole rather than focusing on isolated organ system issues. Method: We present a case report of a 6-month-old girl who, after an uneventful pregnancy and normal prenatal ultrasound, presented with cardiac insufficiency. Following extensive investigations and multiple surgical interventions, DiGeorge syndrome was diagnosed at 9 months of age. Results: The patient’s diagnosis was delayed due to the lack of prenatal markers and the reliance on separate investigations of affected organ systems. Despite several interventions aimed at managing her symptoms, the final diagnosis was made after observing the association of multiple clinical features and conducting comprehensive genetic testing. Conclusions: This case underscores the importance of a holistic approach to diagnosis, which involves a thorough patient history, integration of diverse diagnostic tests, and recognition of the syndrome’s multi-system nature. It highlights the necessity for improved diagnostic protocols and increased awareness in regions with limited access to advanced genetic testing to prevent delays in identifying DiGeorge syndrome and to facilitate timely and appropriate management.展开更多
[Objective]To study the effects of homologous chromosomes 7 （7A,7B and 7D） on wheat photosynthesis and provide theoretical basis for breeding high photosynthetic efficiency wheat by genetic,physiological and biochem...[Objective]To study the effects of homologous chromosomes 7 （7A,7B and 7D） on wheat photosynthesis and provide theoretical basis for breeding high photosynthetic efficiency wheat by genetic,physiological and biochemical means. [Method]The Triticum asetivum cultivar Chinese Spring wheat and nullisomic wheat （N7A,N7B and N7D） were planted in greenhouse. The photosynthetic indexes were determined at early filling stage. [Result]The photosynthetic rate （Pn）,stomatal conductance （Gs）,primary photochemical efficiency （Fv/Fm）,actual chemical efficiency of photosystem II （ФPS II） and apparent electron transfer rate of photosystem II （ETR） were significantly lower in the N7A and N7B than in the Chinese Spring （P0.05）. The photosynthetic rate and stomatal conductance was significantly lower in the N7D than in the Chinese Spring （P0.05）. The Fv/Fm,ФPS II,ETR of N7D were higher than that of the Chinese Spring without significant difference. [Conclusion]The homologous chromosomes 7A and 7B have positive effects on photosynthetic rate and have relationship with stomatal conductance and photoreaction （chlorophyll fluorescence parameters）. The homologous chromosome 7D has negative effects on photosynthetic rate,which is mainly related to stomatal conductance rather than photoreaction.展开更多
卵巢癌是女性生殖系统肿瘤中死亡率最高的肿瘤,由于卵巢组织的解剖与内分泌的复杂性使卵巢癌的早期诊断极为困难因此,寻找卵巢恶性肿瘤早期诊断指标已经成为研究热点。间隙连接蛋白43（connexin 43,Cx43）为一种细胞间隙连接蛋白,多种...卵巢癌是女性生殖系统肿瘤中死亡率最高的肿瘤,由于卵巢组织的解剖与内分泌的复杂性使卵巢癌的早期诊断极为困难因此,寻找卵巢恶性肿瘤早期诊断指标已经成为研究热点。间隙连接蛋白43（connexin 43,Cx43）为一种细胞间隙连接蛋白,多种肿瘤细胞中都有间隙连接蛋白43表达的下降与缺失[1]。同源磷酸酶-张力蛋白（phosphatase and tensin homolog deleted on chromosome ten,展开更多
The agp gene encoding the ADP-glucose pyrophosphorylase involved in cyanobacterial glycogen synthesis was amplified by PCR. The resulting agp fragment was cloned in plasmid pUC118 to generate plasmid pUCA. Part of the...The agp gene encoding the ADP-glucose pyrophosphorylase involved in cyanobacterial glycogen synthesis was amplified by PCR. The resulting agp fragment was cloned in plasmid pUC118 to generate plasmid pUCA. Part of the fragment within the agp DNA was deleted and replaced by an erythromycin resistance cassette to generate plasmid pUCAE, which was used to transform the Synechocystis sp. PCC 6803 wild-type strain and a mutant with resistance to erythromycin was obtained. PCR analysis of the genomic DNA from the resulting mutant indicated that the appropriate deletion and insertion indeed had occurred. The cell growth and Chl a, glycogen content in the mutant showed difference from those in the wild-type strain. The obtained biomass as well as the Chl a content in the mutant strain was higher than that of the wild-type strain, which suggested that the photosynthesis efficiency in the agp(-) strain was higher than that in the wild-type strain. No glycogen was found in the mutant, providing evidence for the correction of the mutant in physiological level.展开更多
Objective： To search for a biomarker for colorectal cancer. Methods： The MSP, SSCP and deletion tests with serum have been taken simultaneously in 100 cases of colorectal cancer and 2 groups of controls, as well as ...Objective： To search for a biomarker for colorectal cancer. Methods： The MSP, SSCP and deletion tests with serum have been taken simultaneously in 100 cases of colorectal cancer and 2 groups of controls, as well as the specimens of 26 cancer tissues and 22 paracancerous tissues and 29 cases of benign disease tissues for a contrast. Results： The aberrant methylation rate of P16 in the serum was 69.00%, deletion rate 4.00% and suspicious point mutation rate 15.00% in colorectal cancer patients. The data of cancer tissues were the same as those of the serum, but in paracancerous tissue those were significantly lower. In 10 cases, sequencing analysis revealed that there were 3 cases of missense, one case of frameshift and one case of nonsense. Among them, four cases had P16 protein deletion. As a tumor marker, the sensitivity of combined use of three methods was 88.00%, specificity 96.87% and accuracy 90.15%. The combined use of MSP and SSCP could obtain the same results. Conclusion： The content of DNA in serum is minimal, but it reflects the tumor burden of patients. The 10^-3 fragments of DNA could be detected in the serum by MSP. It can be used in the clinical diagnosis or popular investigation, and long-term postoperative follow-up.展开更多
文摘In the words of the late Sir Colin Blakemore,neurologists have historically sought to infer brain functions in a manner akin to to king a hammer to a computeranalyzing localized anatomical lesions caused by trauma,tumors,or strokes,noting deficits,and inferring what functions certain brain regions may be responsible for.This approach exemplifies a deletion heuristic,where the absence of a specific function reveals insights about the underlying structures or mechanisms responsible for it.By observing what is lost when a particular brain region is damaged,throughout the history of the field,neurologists have pieced together the intricate relationship between anatomy and function.
基金Supported by National Natural Science Foundation of China(No.82070964)Shaanxi Provincial Outstanding Youth Science Foundation Project(No.2022JC-60)+1 种基金Shaanxi International Science and Technology Cooperation Program Project(No.2024GHYBXM-20)Shaanxi Provincial Education Department Youth Innovation Team Research Project(No.23JP151).
文摘Glaucoma is a group of diseases characterized by progressive optic nerve degeneration,with the characteristic pathological change being death of retinal ganglion cells(RGCs),which ultimately causes visual field loss and irreversible blindness.Elevated intraocular pressure(IOP)remains the most important risk factor for glaucoma,but the exact mechanism responsible for the death of RGCs is currently unknown.Neurotrophic factor deficiency,impaired mitochondrial structure and function,disrupted axonal transport,disturbed Ca2+homeostasis,and activation of apoptotic and autophagic pathways play important roles in RGC death in glaucoma.This review was conducted using Web of Science,PubMed,Project,and other databases to summarize the relevant mechanisms of death of RGCs in glaucoma,in addition to outlining protective treatments to improve the degradation of RGCs.
文摘The original online version of this article was revised:In this article the caption to Fig 14 was inadvertently swapped.The space should be added after")"and the letter"f)"at the end should be deleted.In this article the wrong figure appeared as Fig.15;the figure should have appeared as shown below.
基金Supported by Capital’s Funds for Health Improvement and Research(No.2024-2-4087)Central Guidance for Local Scientific and Technological Development Funding Projects(No.2022ZY0026).
文摘Dear Editor,X-linked retinoschisis(XLRS)is a rare X-linked recessive disorder predominantly afflicting young males.The schisis of the retinal layers is a result of deleterious mutations in the RS1 gene.Insufficient epidemiological data has caused significant variation in reported global prevalence,with estimates fluctuating between 1 in 5000 and 1 in 30000 individuals[1].A large follow-up multicenter study recently published has yielded noteworthy findings concerning the phenotypic spectrum,long-term natural history,and genotype of XLRS.The investigation revealed a significant variability in visual function and disease progression,with particular variants of the RS1 gene displaying diverse phenotypic expressions,suggesting the intricate genetic basis underlying this disorder[2].The range of visual impairments associated with XLRS is extensive,varying from minor to severe.This condition is also characterized by specific retinal abnormalities,including radial streaks emanating from a divided central fovea,schisis affecting the inner layers of the retina in peripheral areas,and a diminished amplitude ratio of b-to a-wave,or even an electronegative electroretinography(ERG)[3].At their initial consultation,the majority of individuals with XLRS exhibit visual acuity(VA)levels between 20/60 and 20/120.However,there is a significant diversity in the condition’s presentation and progression,even among relatives,with VA levels spanning from near-normal to complete loss of sight[4-5].While vision tends to be reasonably consistent over several years for those with XLRS,there is documentation of a more rapid decline in later adulthood,specifically during the fourth and fifth decades,due to central retinal degeneration[5-7].Moreover,those with XLRS face an elevated risk for serious visual issues,such as retinal detachment,vitreous hemorrhages,and neovascular glaucoma[4].Female carriers could be found with slightly abnormal retinal changes without clinical symptoms[5].Even within the same family,the manifestation and progression of the condition can vary greatly,with individuals experiencing anything from nearly normal vision to complete loss of sight[8-9].Earlier investigations have revealed that retinoschisisrelated cystoid degeneration can impact multiple layers of the retina,beginning at the retinal nerve fiber zone and continuing to the nuclear stratum,with considerable fluctuation in the severity of the schisis[10-13].
文摘BACKGROUND Acute myeloid leukemia(AML)is a complicated disease with uncontrolled hematopoietic precursor proliferation induced by various genetic alterations.Runt-related transcription factor-1(RUNX1)is commonly disrupted by chromosomal translocations in hematological malignancies.AIM To characterize RUNX1 gene rearrangements and copy number variations in newly diagnosed adult AML patients,with an emphasis on the impact of clinical and laboratory features on the outcome.METHODS Fluorescence in situ hybridization was used to test RUNX1 gene alterations in 77 newly diagnosed adult AML cases.NPM1,FLT3/ITD,FLT3/TKD,and KIT mutations were tested by PCR.Prognostic clinical and laboratory findings were studied in relation to RUNX1 alterations.RESULTS RUNX1 abnormalities were detected by fluorescence in situ hybridization in 41.6%of patients:20.8%had translocations,22.1%had amplification,and 5.2%had deletion.Translocations prevailed in AML-M2(P=0.019)with a positive expression of myeloperoxidase(P=0.031),whereas deletions dominated in M4 and M5 subtypes(P=0.008)with a positive association with CD64 expression(P=0.05).The modal chromosomal number was higher in cases having amplifications(P=0.007)and lower in those with deletions(P=0.008).RUNX1 abnormalities were associated with complex karyotypes(P<0.001)and were mutually exclusive of NPM1 mutations.After 44 months of follow-up,RUNX1 abnormalities affected neither patients’response to treatment nor overall survival.CONCLUSION RUNX1 abnormalities were mutually exclusive of NPM1 mutations.RUNX1 abnormalities affected neither patients’response to treatment nor overall survival.
文摘BACKGROUND Each year,more than a million people are diagnosed with gastric cancer(GC)worldwide,and the incidence of this disease is projected to increase.Helicobacter pylori(H.pylori)is the major cause of GC.Managing infections caused by H.pylori and investigating their contribution to GC carcinogenesis are crucial for advancing diagnosis and treatment.Deleted in malignant brain tumors 1(DMBT1)is associated with the development of H.pylori and GC.However,the precise underlying mechanism is unclear.AIM To explore the role of DMBT1,as modulated by H.pylori,in the development,proliferation,and metastasis of GC.METHODS Utilizing human GC cells,DMBT1 gene silencing,and H.pylori treatment,four cell groups(control,H.pylori,si-DMBT1,and H.pylori+si-DMBT1)were subjected to cell counting kit-8,scratch,and Transwell assays.The DMBT1 expression was assessed by quantitative real-time polymerase chain reaction and Western blot.RESULTS In cellular tests,H.pylori+si-DMBT1 showed the greatest ability to proliferate,migration,and invasion capabilities,followed by the si-DMBT1,H.pylori,and control groups.DMBT1 mRNA was found to be the highest in control group,next in si-DMBT1,H.pylori and H.pylori+si-DMBT1,while H.pylori+si-DMBT1 showed the least expression.The results the Western blot assay showed a consistent trend of decreasing DMBT1 protein and mRNA levels.CONCLUSION Through inhibition of DMBT1,H.pylori could enhance GC’s proliferation,metastasis and invasion.Our findings revealed a novel connection between H.pylori infection,inflammation,and GC.
基金supported by grants(92168103,32171417,2019CXJQ01)from the National Nature Science Foundation of China,Shanghai Municipal GovernmentPeak Disciplines(Type IV)of Institutions of Higher Learning in Shanghai.
文摘Genome rearrangement is an important process that leads to genetic diversity,including mutation-related insertions,deletions,or inversions in the genome[1,2].
文摘BACKGROUND Rett syndrome is a monogenic X-linked dominant condition that affects 1/(10000-15000)girls due to de novo mutations in the methyl-CpG binding protein 2(MECP2)gene mapped to chromosome Xq28.The disease-causing gene was identified as a mutation in the MECP2 gene,which is found in approximately 80%of patients diagnosed with Rett syndrome.Although chromosomal changes resulting in del(15)(q11q13)are usually associated with Angelman and Prader-Willi syndrome,very few cases,if any,of Rett syndrome with terminal 15q22-qter deletion have been published in English literature.CASE SUMMARY In this study,we report an unusual and rare clinical presentation of Rett syndrome in a 12-year-old Sudanese girl.The patient was brought in by her parents,complaining of gradual onset of abnormal walking,abnormal hand movement,loss of speech,and mental retardation for ten years.There was no reported history of convulsions or loss of consciousness.Clinical examination revealed microcephaly with no other apparent dysmorphic features,intact cranial nerves,and abnormal gait.She showed repetitive and stereotyped behaviors,including hand flapping,stimming,and chest pounding,which were concomitant with autism spectrum disorder.Magnetic resonance imaging and electroencephalography investigations were normal,and cytogenetic analysis showed 46,XX,del(15)(q22qter).Further molecular analysis using whole sequencing of MECP2 revealed an alteration cytosine>thymine at nucleotide 401,leading to phenylalanine replacing a serine at amino acid position 134.CONCLUSION This case,the first reported instance of Rett syndrome in Sudan,is of significant interest.The patient carries both the MECP2 gene mutation and the chromosome 15q22-qter deletion,which may explain the autistic behavior with atypical presentation of Rett syndrome.This report expands the genetic diversity of Rett syndrome,demonstrating how co-occurring 15q22-qter deletions can reshape MECP2-associated phenotypes in Rett syndrome.
基金supported by the Special Key Project for Technological Innovation and Application Development in Chongqing,China(CSTB2022TIAD-KPX0011)the Special Fund for Youth Team of the Southwest Universities,China(SWU-XJPY202306)+1 种基金the Natural Science Foundation of Chongqing,China(cstc2021jcyj-msxmX0583)the Fundamental Research Funds for the Central Universities of Southwest University,China(S202210635326)。
文摘The female inflorescence,or ear,of maize develops no branch meristem(BM),which differs from the male inforescence,or tassel.While the mutations of some well documented genes,such as fea2/3/4 and ramosa1/2/3,can cause the branched architecture of ears in maize,such mutations also change the normal phenotypic performance of the tassels.In the present study,a natural maize mutant with branched ears,named branched ear1(be1),was characterized.be1 shows several branched ears at the base of the central ear with unchanged architecture of the tassels.Besides,both the branched and central ears of be1 possess regularly arranged kerels.The phenotypic characteristics of be1 differ completely from those reported mutants of fasciated ears or RAMOSA-like ears in maize.An SEM survey at the very early development stage showed that meristems with three protrusions,similar to the BM in tassels,were present during the development of the branched ears in be1.Gene mapping and sequence alignment suggested that TEOSINTE BRANCHED1(TB1)was the candidate gene of BE1.Further verification showed that a be1-specific 31 bp deletion at the downstream of BE1 led to statistically reduced expression of this gene in the immature ear,which serves as the potential causal reason for the branched ears of be1.CRISPR/Cas9-based gene editing downstream of TB1 complemented the phenotypic architecture of branched ears,suggesting that TB1 was the target of BE1,and it was named as Zm TB1be1.The results of the present study implied a novel function of TB1 in female inforescence development,rather than shaping the plant architecture in maize.Meanwhile,further functional dissection of ZmTB1be1might shed new light on TB1,the most famous domestication related gene in maize.
基金supported by the National Natural Science Foundation of China,Nos. 82173806 and U1803281Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Science,Nos. 2021-I2M-1-030 and 2022-I2M-2-002Non-Profit Central Research Institute Fund of Chinese Academy of Medical Sciences,No. 2022-JKCS-08 (all to RL)。
文摘Long noncoding RNA and microRNA are regulatory noncoding RNAs that are implicated in Alzheimer's disease, but the role of long noncoding RNA-associated competitive endogenous RNA has not been fully elucidated. The long noncoding RNA growth arrest-specific 5(GAS5) is a member of the 5′-terminal oligopyrimidine gene family that may be involved in neurological disorders, but its role in Alzheimer's disease remains unclear. This study aimed to investigate the function of GAS5 and construct a GAS5-associated competitive endogenous RNA network comprising potential targets. RNA sequencing results showed that GAS5 was upregulated in five familial Alzheimer's disease(5×FAD) mice, APPswe/PSEN1dE9(APP/PS1) mice, Alzheimer's disease-related APPswe cells, and serum from patients with Alzheimer's disease. Functional experiments with targeted overexpression and silencing demonstrated that GAS5 played a role in cognitive dysfunction and multiple Alzheimer's disease-associated pathologies, including tau hyperphosphorylation, amyloid-beta accumulation, and neuronal apoptosis. Mechanistic studies indicated that GAS5 acted as an endogenous sponge by competing for microRNA-23b-3p(miR-23b-3p) binding to regulate its targets glycogen synthase kinase 3beta(GSK-3β) and phosphatase and tensin homologue deleted on chromosome 10(PTEN) expression in an Argonaute 2-induced RNA silencing complex(RISC)-dependent manner. GAS5 inhibited miR-23b-3p-mediated GSK-3β and PTEN cascades with a feedforward PTEN/protein kinase B(Akt)/GSK-3β linkage. Furthermore, recovery of GAS5/miR-23b-3p/GSK-3β/PTEN pathways relieved Alzheimer's disease-like symptoms in vivo, indicated by the amelioration of spatial cognition, neuronal degeneration, amyloid-beta load, and tau phosphorylation. Together, these findings suggest that GAS5 promotes Alzheimer's disease pathogenesis. This study establishes the functional convergence of the GAS5/miR-23b-3p/GSK-3β/PTEN pathway on multiple pathologies, suggesting a candidate therapeutic target in Alzheimer's disease.
基金supported by the Chongqing Science and Technology CommitteeNatural Science Foundation of Chongqing,No.cstc2021jcyj-msxmX0065 (to YL)。
文摘Autism spectrum disorders are a group of neurodevelopmental disorders involving more than 1100 genes,including Ctnnd2 as a candidate gene.Ctnnd2knockout mice,serving as an animal model of autis m,have been demonstrated to exhibit decreased density of dendritic spines.The role of melatonin,as a neuro hormone capable of effectively alleviating social interaction deficits and regulating the development of dendritic spines,in Ctnnd2 deletion-induced nerve injury remains unclea r.In the present study,we discove red that the deletion of exon 2 of the Ctnnd2 gene was linked to social interaction deficits,spine loss,impaired inhibitory neurons,and suppressed phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt) signal pathway in the prefrontal cortex.Our findings demonstrated that the long-term oral administration of melatonin for 28 days effectively alleviated the aforementioned abnormalities in Ctnnd2 gene-knockout mice.Furthermore,the administration of melatonin in the prefro ntal cortex was found to improve synaptic function and activate the PI3K/Akt signal pathway in this region.The pharmacological blockade of the PI3K/Akt signal pathway with a PI3K/Akt inhibitor,wo rtmannin,and melatonin receptor antagonists,luzindole and 4-phenyl-2-propionamidotetralin,prevented the melatonin-induced enhancement of GABAergic synaptic function.These findings suggest that melatonin treatment can ameliorate GABAe rgic synaptic function by activating the PI3K/Akt signal pathway,which may contribute to the improvement of dendritic spine abnormalities in autism spectrum disorders.
基金Supported by Chongqing Fundamental Research Funds,No.jbky20210001Key Programs of Technological Innovation and Application Development of Chongqing,China,No.cstc2021jscx-dxwtBX0016+2 种基金Natural Science Foundation of Chongqing,No.cstc2021jcyjmsxmX0793Science and Technology Project in Social Livelihood of Bishan District,Chongqing,China,No.BSKJ0078 and No.BSKJ0075Performance Incentive-oriented Project of Chongqing,No.jxjl20220007。
文摘BACKGROUND The modified Xiaoyao San(MXS)formula is an adjuvant drug recommended by the National Health Commission of China for the treatment of liver cancer,which has the effect of preventing postoperative recurrence and metastasis of hepatocellular carcinoma and prolonging patient survival.However,the molecular mechanisms underlying that remain unclear.AIM To investigate the role and mechanisms of MXS in ameliorating hepatic injury,steatosis and inflammation.METHODS A choline-deficient/high-fat diet-induced rat nonalcoholic steatohepatitis(NASH)model was used to examine the effects of MXS on lipid accumulation in primary hepatocytes.Liver tissues were collected for western blotting and immunohisto chemistry(IHC)assays.Lipid accumulation and hepatic fibrosis were detected using oil red staining and Sirius red staining.The serum samples were collected for biochemical assays and NMR-based metabonomics analysis.The inflammation/lipid metabolism-related signaling and regulators in liver tissues were also detected to reveal the molecular mechanisms of MXS against NASH.RESULTS MXS showed a significant decrease in lipid accumulation and inflammatory response in hepatocytes under metabolic stress.The western blotting and IHC results indicated that MXS activated AMPK pathway but inhibited the expression of key regulators related to lipid accumulation,inflammation and hepatic fibrosis in the pathogenesis of NASH.The metabonomics analysis systemically indicated that the arachidonic acid metabolism and steroid hormone synthesis are the two main target metabolic pathways for MXS to ameliorate liver inflammation and hepatic steatosis.Mechanistically,we found that MXS protected against NASH by attenuating the sex hormone-related metabolism,especially the metabolism of male hormones.CONCLUSION MXS ameliorates inflammation and hepatic steatosis of NASH by inhibiting the metabolism of male hormones.Targeting male hormone related metabolic pathways may be the potential therapeutic approach for NASH.
文摘Erratum to:Rare Met.(2014)1:1-15 D0I10.1007/s12598-013-0217-8 Due to the negligence of the first author,the address for the corresponding author in the final proof version was duplicate with wrong one.Apologize for this error and the following address should be deleted:R.-M.Wang,Institute of Metal Research,Chinese Academy of Sciences,Shenyang 110016,China.
文摘Background: DiGeorge syndrome (also known as velo-cardio-facial syndrome) is a rare multisystem genetic disorder occurring in approximately 1 in 4000 to 1 in 6000 live births [1]. Although advances in genetic screening have improved diagnosis in developed countries, the condition remains underdiagnosed in developing nations such as the Republic of Moldova, where access to genetic testing and family planning services is limited. Routine prenatal screening usually includes regular ultrasounds, monitoring of blood pressure, complete blood counts, coagulation studies, glucose, urine protein, and urine culture. Current ultrasound techniques have limitations in detecting this syndrome due to variability in interpretation, and genetic testing is often performed based on clinical discretion. The ultrasound could potentially point towards a genetic problem, as in DiGeorge, if multiple cardiac malformations are spotted in utero, but most cases such as this one are diagnosed after birth while being described as totally normal on prenatal ultrasound. Purpose: This study aims to highlight the diagnostic challenges and the need for comprehensive evaluation in identifying DiGeorge syndrome, emphasizing the importance of considering the syndrome as a whole rather than focusing on isolated organ system issues. Method: We present a case report of a 6-month-old girl who, after an uneventful pregnancy and normal prenatal ultrasound, presented with cardiac insufficiency. Following extensive investigations and multiple surgical interventions, DiGeorge syndrome was diagnosed at 9 months of age. Results: The patient’s diagnosis was delayed due to the lack of prenatal markers and the reliance on separate investigations of affected organ systems. Despite several interventions aimed at managing her symptoms, the final diagnosis was made after observing the association of multiple clinical features and conducting comprehensive genetic testing. Conclusions: This case underscores the importance of a holistic approach to diagnosis, which involves a thorough patient history, integration of diverse diagnostic tests, and recognition of the syndrome’s multi-system nature. It highlights the necessity for improved diagnostic protocols and increased awareness in regions with limited access to advanced genetic testing to prevent delays in identifying DiGeorge syndrome and to facilitate timely and appropriate management.
基金Supported by Excellent Young Academic Leaders Project of Shanxi Province~~
文摘[Objective]To study the effects of homologous chromosomes 7 （7A,7B and 7D） on wheat photosynthesis and provide theoretical basis for breeding high photosynthetic efficiency wheat by genetic,physiological and biochemical means. [Method]The Triticum asetivum cultivar Chinese Spring wheat and nullisomic wheat （N7A,N7B and N7D） were planted in greenhouse. The photosynthetic indexes were determined at early filling stage. [Result]The photosynthetic rate （Pn）,stomatal conductance （Gs）,primary photochemical efficiency （Fv/Fm）,actual chemical efficiency of photosystem II （ФPS II） and apparent electron transfer rate of photosystem II （ETR） were significantly lower in the N7A and N7B than in the Chinese Spring （P0.05）. The photosynthetic rate and stomatal conductance was significantly lower in the N7D than in the Chinese Spring （P0.05）. The Fv/Fm,ФPS II,ETR of N7D were higher than that of the Chinese Spring without significant difference. [Conclusion]The homologous chromosomes 7A and 7B have positive effects on photosynthetic rate and have relationship with stomatal conductance and photoreaction （chlorophyll fluorescence parameters）. The homologous chromosome 7D has negative effects on photosynthetic rate,which is mainly related to stomatal conductance rather than photoreaction.
文摘卵巢癌是女性生殖系统肿瘤中死亡率最高的肿瘤,由于卵巢组织的解剖与内分泌的复杂性使卵巢癌的早期诊断极为困难因此,寻找卵巢恶性肿瘤早期诊断指标已经成为研究热点。间隙连接蛋白43（connexin 43,Cx43）为一种细胞间隙连接蛋白,多种肿瘤细胞中都有间隙连接蛋白43表达的下降与缺失[1]。同源磷酸酶-张力蛋白（phosphatase and tensin homolog deleted on chromosome ten,
文摘The agp gene encoding the ADP-glucose pyrophosphorylase involved in cyanobacterial glycogen synthesis was amplified by PCR. The resulting agp fragment was cloned in plasmid pUC118 to generate plasmid pUCA. Part of the fragment within the agp DNA was deleted and replaced by an erythromycin resistance cassette to generate plasmid pUCAE, which was used to transform the Synechocystis sp. PCC 6803 wild-type strain and a mutant with resistance to erythromycin was obtained. PCR analysis of the genomic DNA from the resulting mutant indicated that the appropriate deletion and insertion indeed had occurred. The cell growth and Chl a, glycogen content in the mutant showed difference from those in the wild-type strain. The obtained biomass as well as the Chl a content in the mutant strain was higher than that of the wild-type strain, which suggested that the photosynthesis efficiency in the agp(-) strain was higher than that in the wild-type strain. No glycogen was found in the mutant, providing evidence for the correction of the mutant in physiological level.
基金This study was supported by a grant from Science and Research Foundation of Shanxi Province (No. 022075)
文摘Objective： To search for a biomarker for colorectal cancer. Methods： The MSP, SSCP and deletion tests with serum have been taken simultaneously in 100 cases of colorectal cancer and 2 groups of controls, as well as the specimens of 26 cancer tissues and 22 paracancerous tissues and 29 cases of benign disease tissues for a contrast. Results： The aberrant methylation rate of P16 in the serum was 69.00%, deletion rate 4.00% and suspicious point mutation rate 15.00% in colorectal cancer patients. The data of cancer tissues were the same as those of the serum, but in paracancerous tissue those were significantly lower. In 10 cases, sequencing analysis revealed that there were 3 cases of missense, one case of frameshift and one case of nonsense. Among them, four cases had P16 protein deletion. As a tumor marker, the sensitivity of combined use of three methods was 88.00%, specificity 96.87% and accuracy 90.15%. The combined use of MSP and SSCP could obtain the same results. Conclusion： The content of DNA in serum is minimal, but it reflects the tumor burden of patients. The 10^-3 fragments of DNA could be detected in the serum by MSP. It can be used in the clinical diagnosis or popular investigation, and long-term postoperative follow-up.
