2021年老挝M_(S)6.0地震序列研究

云南地震活动与周边强震存在“构造相连,动力同源”的特征,研究周边强震的序列演化特征及发震构造,对云南地区地震研究具有重要意义。2021年12月24日老挝M_(S)6.0地震发生在滇西南地区的NW向整董断裂附近,震源机制解显示,此次地震是一次走滑型破裂事件,破裂方向与区域构造特征一致。老挝M_(S)6.0地震序列属于前震-主震-余震型序列,主震前震中附近出现3~4级地震非常活跃的现象,前震序列参数计算显示b值波动相对幅度较大,h值出现“上翘”形态,而余震序列b值和h值变化均相对平稳,主震的同震库伦应力结果表明老挝地震可能对云南地区有应力加载作用。

Intergeneric chromosome-specific painting reveals differential chromosomal transmission from Tripidium arundinaceum in sugarcane progeny

Sugarcane has recently attracted increasing attention for its potential as a source of sugar and bioethanol,so increasing its yield is essential to ensure the sugar security and bioenergy production.Intergeneric hybridization is a highly efficient method to produce new genetic variants of crop plants,particularly those species with high ploidy such as sugarcane(Saccharum spp.).Tripidium arundinaceum exhibits many desirable agronomic traits,and has been widely studied to produce hybrids with improved stress tolerance and other characteristics in sugarcane breeding.However,the genetic relationship between T.arundinaceum and Saccharum species,and the individual T.arundinaceum chromosomal compositions in sugarcane hybrids are still elusive.Here we used whole-genome single-nucleotide polymorphisms(SNPs)to ascertain the phylogenetic relationships between these species and found that T.arundinaceum is more closely related to Saccharum than Sorghum,in contrast to the previous narrow genetic analyses using chloroplast DNA.Additionally,oligonucleotide(oligo)-based chromosome-specific painting derived from Saccharum officinarum was able to distinctly identify the chromosomes of T.arundinaceum.We developed the oligo-genomic in situ hybridization(GISH)system for the first time,to unveil the novel chromosome translocations and the transmission of individual T.arundinaceum chromosomes in sugarcane progeny.Notably,we discovered that the chromosomal transmission of T.arundinaceum exhibited several different inheritance modes,including n,2n,and over 2n in the BC1 progenies.Such inheritance patterns may have resulted from first division restitution(FDR)or FDR+nondisjunction of a chromosome with the sister chromatids in the second meiosis division/second division restitution(FDR+NSC/SDR)model during meiosis.These results will be of substantial benefit for the further selection of T.arundinaceum chromosomes for sugarcane genetic improvement.

Vitamin and zeatin treatments promote colchicine-induced haploid chromosome doubling in maize

Doubled haploid(DH)technology is an efficient method used in commercial maize breeding.Chromosome doubling is a vital step of DH technology;however,the underlying processes regulating chromosome doubling of haploid is still not well understood,which is key to optimize the technology.In this study,the immature haploid embryos of the maize inbred line Zheng58 treated with amiprophos-methyl(APM)or colchicine were used to analyze transcriptomic and metabolomic changes,75 and 60 differential expressed metabolites(DEMs)were identified between control treatment,respectively.Most differentially expressed genes(DEGs)related to artificial chromosome doubling were down regulated;these were mainly involved in mitosis process.Both DEMs and DEGs co-expression analyses showed that,compared to controls,zeatin biosynthesis and cofactor and vitamin metabolism were significantly enriched in both APM and colchicine treatments.In a parallel experiment,exogenous vitamins including thiamine,nicotinic acid,vitamin B6,or trans-zeatin were added to colchicine treatment;there were synergistic effects between vitamins or zeatin and colchicine in haploid artificial chromosome doubling.These results provide novel insights in exploring the molecular responses to antimitotic reagents at both the transcriptomic and metabolomic levels.In addition,the application efficiency of haploid breeding will be greatly improved by the key factors for artificial chromosome doubling.

Characterization of a 4.1 Mb inversion harboring the stripe rust resistance gene YR86 on wheat chromosome 2AL

Wheat cultivar Zhongmai 895 was earlier found to carry YR86 in an 11.6 Mb recombination-suppressed region on chromosome 2AL when crossed with Yangmai 16.To fine-map the YR86 locus,we developed two large F2 populations from crosses Emai 580/Zhongmai 895 and Avocet S/Zhongmai 895.Remarkably,both populations exhibited suppressed recombination in the same 2AL region.Collinearity analysis across Chinese Spring,Aikang 58,and 10+wheat genomes revealed a 4.1 Mb chromosomal inversion spanning 708.5-712.6 Mb in the Chinese Spring reference genome.Molecular markers were developed in the breakpoint and were used to assess a wheat cultivar panel,revealing that Chinese Spring,Zhongmai 895,and Jimai 22 shared a common sequence named InvCS,whereas Aikang 58,Yangmai 16,Emai 580,and Avocet S shared the sequence named InvAK58.The inverted configuration explained the suppressed recombination observed in all three bi-parental populations.Normal recombination was observed in a Jimai 22/Zhongmai 895 F2 population,facilitating mapping of YR86 to a genetic interval of 0.15 cM corresponding to 710.27-712.56 Mb falling within the inverted region.Thirty-three high-confidence genes were annotated in the interval using the Chinese Spring reference genome,with six identified as potential candidates for YR86 based on genome and transcriptome analyses.These results will accelerate map-based cloning of YR86 and its deployment in wheat breeding.

Investigation of sex determination in starry flounder(Platichthys stellatus)reveals sex chromosome evolution in Pleuronectiformes and identifies a sex-specific marker

The identification of sex chromosomes is fundamental for exploring the mechanism and evolution of sex determination.Platichthys stellatus,a species exhibiting clear sexual dimorphism and homomorphic chromosome pairs,has received limited research concerning its sex determination mechanisms.Clarifying the sex chromosome of P.stellatus will enhance our understanding of sex chromosome evolution in Pleuronectiformes.This study employed whole-genome resequencing to investigate the sex chromosome and sex determination system in P.stellatus.Notably,Chr23 was identified as the sex chromosome in P.stellatus,with the sex-determining region(SDR)occupying 48.1%of the chromosome and featuring an XX/XY system.Sex chromosome turnover was observed within Pleuronectiformes,with P.stellatus,Verasper variegatus,and Hippoglossus hippoglossus sharing a common ancestral karyotype.No inversions were detected within the SDR of P.stellatus,although chromosomal rearrangements between sex chromosomes and autosomes were identified.Additionally,a sex-specific marker for P.stellatus was ascertained,enabling genetic sex identification,with significant implications for improving breeding programs and aquaculture practices.

Loss of heterozygosity for chromosomes 16q in Wilms tumors predicts outcomes:A meta-analysis

BACKGROUND The research findings suggest that the prognosis of children with Wilms tumor(WT)is affected by various factors.Some scholars have indicated that loss of heterozygosity(LOH)on chromosome 16q is associated with a poor prognosis in patients with WT.AIM To further elucidate this relationship,we conducted a meta-analysis.METHODS This meta-analysis was registered in INPLASY(INPLASY2023100060).We systematically searched databases including Embase,PubMed,Web of Science,Cochrane,and Google Scholar up to May 31,2020,for randomized trials reporting any intrapartum fetal surveillance approach.The meta-analysis was performed within a frequentist framework,and the quality and network inconsistency of trials were assessed.Odds ratios and 95%CIs were calculated to report the relationship between event-free survival and 16q LOH in patients with WT.RESULTS Eleven cohort studies were included in this meta-analysis to estimate the relationship between event-free survival and 16q LOH in patients with WT(I^(2)=25%,P<0.001).As expected,16q LOH can serve as an effective predictor of eventfree survival in patients with WT(risk ratio=1.95,95%CI:1.52–2.49,P<0.001).CONCLUSION In pediatric patients with WT,there exists a partial correlation between 16q LOH and an unfavorable treatment prognosis.Clinical detection of 16q chromosome LOH warrants increased attention to the patient’s prognosis.

Knock-in of exogenous sequences based on CRISPR/Cas9 targeting autosomal genes and sex chromosomes in the diamondback moth,Plutella xylostella

Genetic pest control strategies based on precise sex separation and only releasing sterile males can be accomplished by site-specific genome editing.In the current study,we showed that the mutation of single-allele Pxfl(2)d can significantly impair the normal mating behavior and testis development in male adults of the notorious cruciferous insect pest Plutella xylostella,in addition to its known functions in the ovarian development in female adults and egg hatching.Subsequent CRISPR/Cas9-based knock-in experiments revealed that site-specific integration of an exogenous green fluorescent protein(GFP)gene into autosomal Pxfl(2)d for labelling mutants could be achieved.However,this gene is not a suitable target for GFP insertion to establish a genetically stable knock-in strain because of the severe decline in reproductive capacity.We further screened for the W-chromosome-linked and Z-chromosome-linked regions to test the knock-in efficiency mediated by CRISPR/Cas9.The results verified that both types of chromosomes can be targeted for the site-specific insertion of exogenous sequences.We ultimately obtained a homozygous knock-in strain with the integration of both Cas9 and cyan fluorescent protein(CFP)expression cassettes on a Z-linked region in P.xylostella,which can also be used for early sex detection.By injecting the sgRNA targeting Pxfl(2)d alone into the eggs laid by female adults of the Z-Cas9-CFP strain,the gene editing efficiency reached 29.73%,confirming the success of expressing a functional Cas9 gene.Taken together,we demonstrated the feasibility of the knock-in of an exogenous gene to different genomic regions in P.xylostella,while the establishment of a heritable strain required the positioning of appropriate sites.This study provides an important working basis and technical support for further developing genetic strategies for insect pest control.

Identification and transferring of a new Fusarium head blight resistance gene FhbRc2 from Roegneria ciliaris 3ScL chromosome arm into common wheat

Fusarium head blight(FHB)threatens wheat production worldwide.Utilization of FHB resistant varieties is the most effective solution for disease control.Owing to the limited sources of FHB resistance,mining of novel resistance genes is crucial.Here,we report an FHB resistance gene from a wild wheat relative species,Roegneria ciliaris and developed FHB resistant germplasm containing this gene.Wheat-R.ciliaris disomic addition line DA3S^(c) showed enhanced type II FHB resistance compared to its sister line 3S^(c)-Null without chromosome 3S^(c),indicating that the resistance was contributed by the addition of 3S^(c).The resistance gene on 3S^(c) was validated using F2 and F2:3 populations derived from the cross between DA3S^(c) and susceptible Aikang 58(a susceptible cultivar),demonstrating that the lines with 3S^(c) had significantly enhanced FHB resistance compared to the individuals without 3S^(c).This was the second resistance gene identified in R.ciliaris,designated FhbRc2.To transfer FhbRc2 to common wheat,we produced a doublemonosomic chromosome population by crossing DA3S^(c) with the Chinese Spring nulli-tetrasomic line N3DT3B.Eight alien chromosome lines containing 3S^(c) were identified using genomic/fluorescence in situ hybridization and 3S^(c)-specific marker analysis.Only the lines carrying the long arm of 3S^(c) conferred FHB resistance,further locating FhbRc2 on 3S^(c)L.A compensating wheat-R.ciliaris Robertsonian translocation line T3DS·3S^(c)L harboring FhbRc2 is developed and provides a potential genetic resource in wheat breeding for enhanced FHB resistance.

2021年漾濞M_(S)6.4地震前重力段差指标量分析及场源特征反演

基于2016-2021年云南地区流动重力重复观测资料,利用流动重力段差变化可视化方法及重力场变化显著性程度指标量G和C值研究了2021年漾濞M_(S)6.4地震前的重力变化,并反演了其与地震孕育相关的场源分布特征,开展了对研究区重力变化及场源特征的定性和定量研究。结果表明:①段差表示法的大小和方向对地下物质的运移方向有一定的指示意义,震前重力指标量呈显著上升,震后又迅速回落,重力变化指标量G和C值可作为评价测网区域重力变化显著性程度的定量依据;②反演得到的重力变化场源位置主要集中在红河断裂带北段至滇西北一带,且表现出与维西-乔后断裂及红河断裂带走向较为一致的分布特征,这可能与地震前中上地壳的深部物质运移相关。

SphK1/S1P/S1PR2信号通路促进肌生成:运动改善骨骼肌健康的新视角

背景:近年来,运动改善骨骼肌的健康已成为学者们关注的一个重要研究内容,适宜的运动对骨骼肌具有积极的作用,其中在运动激活鞘氨醇激酶1(sphingosine kinase1,SphK1)/鞘氨醇-1-磷酸(sphingosine-1-phosphate,S1P)/鞘氨醇-1-磷酸受体2(sphingosine-1-phosphate receptor2,S1PR2)信号通路如何改善骨骼肌的健康,正受到科研人员的重视。目的:研究运动经SphK1/S1P/S1PR2信号通路如何改善骨骼肌的健康,探索治疗相关肌肉疾病的新方法,以改善人的骨骼肌健康。方法:检索Web of Science、PubMed、中国知网、万方和维普数据库从建库至今与文章主题相关的文献,以“signaling pathway,SphK1,S1P,S1PR2,skeletal muscle,satellite cell,myogenesis,exercise”为英文检索词,以“信号通路,SphK1,S1P,S1PR2,骨骼肌,卫星细胞,肌生成,运动”为中文检索词,最终纳入69篇文献进行分析。结果与结论:①SphK1/S1P/S1PR2信号通路是一个复杂的调控网络,通过SphK1催化产生的S1P,与S1PR2等受体的相互作用,触发下游信号转导过程,进而调控细胞、组织、器官和系统的多种生物学功能。②SphK1/S1P/S1PR2信号通路能调控卫星细胞增殖和成肌细胞分化,改善肌生成。③文章通过文献资料调研法分析了SphK1/S1P/S1PR2信号通路的生理基础以及运动对其影响的可能性。急性有氧运动可提高骨骼肌中SphK1的表达,人体和动物研究中已证实急性和长期运动均可提高骨骼肌中S1P水平,另外研究表明长期抗阻运动可提高S1PR2在骨骼肌中的表达,部分实验结果表明急性和长期运动对肌肉或者血液中S1P水平无显著影响,出现不同结果的原因可能是选择的研究对象、方式、强度及频率不同,而具体机制尚不明确。④研究认为,运动能够促进SphK1/S1P/S1PR2信号通路在骨骼肌中的表达,调控下游相关信号通路,并且针对这一信号通路的研究可能为骨骼肌疾病的治疗提供新的策略和方法,从而改善骨骼肌健康。⑤未来应深化对SphK1/S1P/S1PR2信号通路与骨骼肌健康关联的研究,进一步揭示其与卫星细胞、成肌细胞的调控关系及与上下游通路的相互作用,挖掘其临床应用价值,制定康复方案时考虑该通路变化,探索不同运动对该通路的影响机制,并将其作为潜在治疗靶点,结合人体肌肉模型提升研究深度和准确性。

Gut microbiota-astrocyte axis: new insights into age-related cognitive decline

With the rapidly aging human population,age-related cognitive decline and dementia are becoming increasingly prevalent worldwide.Aging is considered the main risk factor for cognitive decline and acts through alterations in the composition of the gut microbiota,microbial metabolites,and the functions of astrocytes.The microbiota–gut–brain axis has been the focus of multiple studies and is closely associated with cognitive function.This article provides a comprehensive review of the specific changes that occur in the composition of the gut microbiota and microbial metabolites in older individuals and discusses how the aging of astrocytes and reactive astrocytosis are closely related to age-related cognitive decline and neurodegenerative diseases.This article also summarizes the gut microbiota components that affect astrocyte function,mainly through the vagus nerve,immune responses,circadian rhythms,and microbial metabolites.Finally,this article summarizes the mechanism by which the gut microbiota–astrocyte axis plays a role in Alzheimer’s and Parkinson’s diseases.Our findings have revealed the critical role of the microbiota–astrocyte axis in age-related cognitive decline,aiding in a deeper understanding of potential gut microbiome-based adjuvant therapy strategies for this condition.

Bo’s abdominal acupuncture treatment for adult-onset Still's disease:A case report

BACKGROUND Adult-onset Still's disease(AOSD)is a rare autoinflammatory disease charac-terized by nonspecific symptoms such as fever,rash,sore throat and arthralgia.This paper reports a clinical case of AOSD successfully treated with Bo’s abdo-minal acupuncture(BAA).CASE SUMMARY We report a 20-year-old man who suffered from cold exposure,presenting with high fever,rash,sore throat,arthralgia,and elevated erythrocyte sedimentation rate,leukocytosis with neutrophilic predominance,elevated ferritin,elevated C-reactive protein,and negative rheumatoid factors.He was diagnosed with AOSD based on the Yamaguchi criteria.After treatment with traditional Chinese medi-cine(TCM)decoction and prednisone acetate tablets,there was some alleviation of sore throat,joint and muscle pain,and fever,but he still had persistent low-grade fever,rash,sore throat and arthralgia.He went to the TCM acupuncture outpatient department to receive BAA.Abdominal acupoints Zhongwan(CV12),Xiawan(CV10),0.5 cm below Xiawan(CV10),Qihai(CV6),Guanyuan(CV4),bilateral Qixue(KI13),bilateral Huaroumen(ST24),bilateral Shangfengshidian(AB1)and bilateral Daheng(SP15)were selected.After 3 months treatment,all symptoms disappeared,and the laboratory examination returned to normal levels.He did not take glucocorticoids or nonsteroidal anti-inflammatory drugs afterwards,and no relapse was observed during the 3-year follow-up period.CONCLUSION BAA can be used as a complementary medical approach for treatment of AOSD.

Role of metabolic dysfunction and inflammation along the liver-brain axis in animal models with obesity-induced neurodegeneration

The interaction between metabolic dysfunction and inflammation is central to the development of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease.Obesity-related conditions like type 2 diabetes and non-alcoholic fatty liver disease exacerbate this relationship.Peripheral lipid accumulation,particularly in the liver,initiates a cascade of inflammatory processes that extend to the brain,influencing critical metabolic regulatory regions.Ceramide and palmitate,key lipid components,along with lipid transporters lipocalin-2 and apolipoprotein E,contribute to neuroinflammation by disrupting blood–brain barrier integrity and promoting gliosis.Peripheral insulin resistance further exacerbates brain insulin resistance and neuroinflammation.Preclinical interventions targeting peripheral lipid metabolism and insulin signaling pathways have shown promise in reducing neuroinflammation in animal models.However,translating these findings to clinical practice requires further investigation into human subjects.In conclusion,metabolic dysfunction,peripheral inflammation,and insulin resistance are integral to neuroinflammation and neurodegeneration.Understanding these complex mechanisms holds potential for identifying novel therapeutic targets and improving outcomes for neurodegenerative diseases.

Differential distribution of PINK1 and Parkin in the primate brain implies distinct roles

The vast majority of in vitro studies have demonstrated that PINK1 phosphorylates Parkin to work together in mitophagy to protect against neuronal degeneration.However,it remains largely unclear how PINK1 and Parkin are expressed in mammalian brains.This has been difficult to address because of the intrinsically low levels of PINK1 and undetectable levels of phosphorylated Parkin in small animals.Understanding this issue is critical for elucidating the in vivo roles of PINK1 and Parkin.Recently,we showed that the PINK1 kinase is selectively expressed as a truncated form(PINK1–55)in the primate brain.In the present study,we used multiple antibodies,including our recently developed monoclonal anti-PINK1,to validate the selective expression of PINK1 in the primate brain.We found that PINK1 was stably expressed in the monkey brain at postnatal and adulthood stages,which is consistent with the findings that depleting PINK1 can cause neuronal loss in developing and adult monkey brains.PINK1 was enriched in the membrane-bound fractionations,whereas Parkin was soluble with a distinguishable distribution.Immunofluorescent double staining experiments showed that PINK1 and Parkin did not colocalize under physiological conditions in cultured monkey astrocytes,though they did colocalize on mitochondria when the cells were exposed to mitochondrial stress.These findings suggest that PINK1 and Parkin may have distinct roles beyond their well-known function in mitophagy during mitochondrial damage.

Comparative proteomic analysis of plasma exosomes reveals the functional contribution of N-acetyl-alpha-glucosaminidase to Parkinson’s disease

Parkinson’s disease is the second most common progressive neurodegenerative disorder,and few reliable biomarkers are available to track disease progression.The proteins,DNA,mRNA,and lipids carried by exosomes reflect intracellular changes,and thus can serve as biomarkers for a variety of conditions.In this study,we investigated alterations in the protein content of plasma exosomes derived from patients with Parkinson’s disease and the potential therapeutic roles of these proteins in Parkinson’s disease.Using a tandem mass tag-based quantitative proteomics approach,we characterized the proteomes of plasma exosomes derived from individual patients,identified exosomal protein signatures specific to patients with Parkinson’s disease,and identified N-acetyl-alpha-glucosaminidase as a differentially expressed protein.N-acetyl-alpha-glucosaminidase expression levels in exosomes from the plasma of patients and healthy controls were validated by enzyme-linked immunosorbent assay and western blot.The results demonstrated that the exosomal N-acetyl-alpha-glucosaminidase concentration was not only lower in Parkinson’s disease,but also decreased with increasing Hoehn-Yahr stage,suggesting that N-acetyl-alpha-glucosaminidase could be used to rapidly evaluate Parkinson’s disease severity.Furthermore,western blot and immunohistochemistry analysis showed that N-acetyl-alpha-glucosaminidase levels were markedly reduced both in cells treated with 1-methyl-4-phenylpyridinium and cells overexpressingα-synuclein compared with control cells.Additionally,N-acetyl-alpha-glucosaminidase overexpression significantly increased cell viability and inhibitedα-synuclein expression in 1-methyl-4-phenylpyridinium-treated cells.Taken together,our findings demonstrate for the first time that exosomal N-acetyl-alpha-glucosaminidase may serve as a biomarker for Parkinson’s disease diagnosis,and that N-acetyl-alpha-glucosaminidase may reduceα-synuclein expression and 1-methyl-4-phenylpyridinium-induced neurotoxicity,thus providing a new therapeutic target for Parkinson’s disease.

Netrin-1 signaling pathway mechanisms in neurodegenerative diseases

Netrin-1 and its receptors play crucial roles in inducing axonal growth and neuronal migration during neuronal development.Their profound impacts then extend into adulthood to encompass the maintenance of neuronal survival and synaptic function.Increasing amounts of evidence highlight several key points:(1)Diminished Netrin-1 levels exacerbate pathological progression in animal models of Alzheimer’s disease and Parkinson’s disease,and potentially,similar alterations occur in humans.(2)Genetic mutations of Netrin-1 receptors increase an individuals’susceptibility to neurodegenerative disorders.(3)Therapeutic approaches targeting Netrin-1 and its receptors offer the benefits of enhancing memory and motor function.(4)Netrin-1 and its receptors show genetic and epigenetic alterations in a variety of cancers.These findings provide compelling evidence that Netrin-1 and its receptors are crucial targets in neurodegenerative diseases.Through a comprehensive review of Netrin-1 signaling pathways,our objective is to uncover potential therapeutic avenues for neurodegenerative disorders.

The autophagy-lysosome pathway:a potential target in the chemical and gene therapeutic strategies for Parkinson’s disease

Parkinson’s disease is a common neurodegenerative disease with movement disorders associated with the intracytoplasmic deposition of aggregate proteins such asα-synuclein in neurons.As one of the major intracellular degradation pathways,the autophagy-lysosome pathway plays an important role in eliminating these proteins.Accumulating evidence has shown that upregulation of the autophagy-lysosome pathway may contribute to the clearance ofα-synuclein aggregates and protect against degeneration of dopaminergic neurons in Parkinson’s disease.Moreover,multiple genes associated with the pathogenesis of Parkinson’s disease are intimately linked to alterations in the autophagy-lysosome pathway.Thus,this pathway appears to be a promising therapeutic target for treatment of Parkinson’s disease.In this review,we briefly introduce the machinery of autophagy.Then,we provide a description of the effects of Parkinson’s disease–related genes on the autophagy-lysosome pathway.Finally,we highlight the potential chemical and genetic therapeutic strategies targeting the autophagy–lysosome pathway and their applications in Parkinson’s disease.

Computed tomography enterography-based radiomics for assessing mucosal healing in patients with small bowel Crohn's disease

BACKGROUND Mucosal healing(MH)is the major therapeutic target for Crohn's disease(CD).As the most commonly involved intestinal segment,small bowel(SB)assessment is crucial for CD patients.Yet,it poses a significant challenge due to its limited accessibility through conventional endoscopic methods.AIM To establish a noninvasive radiomic model based on computed tomography enterography(CTE)for MH assessment in SBCD patients.METHODS Seventy-three patients diagnosed with SBCD were included and divided into a training cohort(n=55)and a test cohort(n=18).Radiomic features were obtained from CTE images to establish a radiomic model.Patient demographics were analysed to establish a clinical model.A radiomic-clinical nomogram was constructed by combining significant clinical and radiomic features.The diagnostic efficacy and clinical benefit were evaluated via receiver operating characteristic(ROC)curve analysis and decision curve analysis(DCA),respectively.RESULTS Of the 73 patients enrolled,25 patients achieved MH.The radiomic-clinical nomogram had an area under the ROC curve of 0.961(95%confidence interval:0.886-1.000)in the training cohort and 0.958(0.877-1.000)in the test cohort and provided superior clinical benefit to either the clinical or radiomic models alone,as demonstrated by DCA.CONCLUSION These results indicate that the CTE-based radiomic-clinical nomogram is a promising imaging biomarker for MH and serves as a potential noninvasive alternative to enteroscopy for MH assessment in SBCD patients.

Nanomaterials-mediated lysosomal regulation:a robust protein-clearance approach for the treatment of Alzheimer’s disease

Alzheimer’s disease is a debilitating,progressive neurodegenerative disorder characterized by the progressive accumulation of abnormal proteins,including amyloid plaques and intracellular tau tangles,primarily within the brain.Lysosomes,crucial intracellular organelles responsible for protein degradation,play a key role in maintaining cellular homeostasis.Some studies have suggested a link between the dysregulation of the lysosomal system and pathogenesis of neurodegenerative diseases,including Alzheimer’s disease.Restoring the normal physiological function of lysosomes hold the potential to reduce the pathological burden and improve the symptoms of Alzheimer’s disease.Currently,the efficacy of drugs in treating Alzheimer’s disease is limited,with major challenges in drug delivery efficiency and targeting.Recently,nanomaterials have gained widespread use in Alzheimer’s disease drug research owing to their favorable physical and chemical properties.This review aims to provide a comprehensive overview of recent advances in using nanomaterials(polymeric nanomaterials,nanoemulsions,and carbon-based nanomaterials)to enhance lysosomal function in treating Alzheimer’s disease.This review also explores new concepts and potential therapeutic strategies for Alzheimer’s disease through the integration of nanomaterials and modulation of lysosomal function.In conclusion,this review emphasizes the potential of nanomaterials in modulating lysosomal function to improve the pathological features of Alzheimer’s disease.The application of nanotechnology to the development of Alzheimer’s disease drugs brings new ideas and approaches for future treatment of this disease.

Glycolytic dysregulation in Alzheimer's disease:unveiling new avenues for understanding pathogenesis and improving therapy

Alzheimer's disease poses a significant global health challenge owing to the progressive cognitive decline of patients and absence of curative treatments.The current therapeutic strategies,primarily based on cholinesterase inhibitors and N-methyl-Daspartate receptor antagonists,offer limited symptomatic relief without halting disease progression,highlighting an urgent need for novel research directions that address the key mechanisms underlying Alzheimer's disease.Recent studies have provided insights into the critical role of glycolysis,a fundamental energy metabolism pathway in the brain,in the pathogenesis of Alzheimer's disease.Alterations in glycolytic processes within neurons and glial cells,including microglia,astrocytes,and oligodendrocytes,have been identified as significant contributors to the pathological landscape of Alzheimer's disease.Glycolytic changes impact neuronal health and function,thus offering promising targets for therapeutic intervention.The purpose of this review is to consolidate current knowledge on the modifications in glycolysis associated with Alzheimer's disease and explore the mechanisms by which these abnormalities contribute to disease onset and progression.Comprehensive focus on the pathways through which glycolytic dysfunction influences Alzheimer's disease pathology should provide insights into potential therapeutic targets and strategies that pave the way for groundbreaking treatments,emphasizing the importance of understanding metabolic processes in the quest for clarification and management of Alzheimer's disease.