Mutations in the microrchidia CW-type zinc finger protein 2(MORC2)gene are the causative agent of Charcot-Marie-Tooth disease type 2Z(CMT2Z),and the hotspot mutation p.S87L is associated with a more seve re spinal mus...Mutations in the microrchidia CW-type zinc finger protein 2(MORC2)gene are the causative agent of Charcot-Marie-Tooth disease type 2Z(CMT2Z),and the hotspot mutation p.S87L is associated with a more seve re spinal muscular atrophy-like clinical phenotype.The aims of this study were to determine the mechanism of the severe phenotype caused by the MORC2 p.S87L mutation and to explore potential treatment strategies.Epithelial cells were isolated from urine samples from a spinal muscular atrophy(SMA)-like patient[MORC2 p.S87L),a CMT2Z patient[MORC2 p.Q400R),and a healthy control and induced to generate pluripotent stem cells,which were then differentiated into motor neuron precursor cells.Next-generation RNA sequencing followed by KEGG pathway enrichment analysis revealed that differentially expressed genes involved in the PI3K/Akt and MAP K/ERK signaling pathways were enriched in the p.S87L SMA-like patient group and were significantly downregulated in induced pluripotent stem cells.Reduced proliferation was observed in the induced pluripotent stem cells and motor neuron precursor cells derived from the p.S87L SMA-like patient group compared with the CMT2Z patient group and the healthy control.G0/G1 phase cell cycle arrest was observed in induced pluripotent stem cells derived from the p.S87L SMA-like patient.MORC2 p.S87Lspecific antisense oligonucleotides(p.S87L-ASO-targeting)showed significant efficacy in improving cell prolife ration and activating the PI3K/Akt and MAP K/ERK pathways in induced pluripotent stem cells.Howeve r,p.S87L-ASO-ta rgeting did not rescue prolife ration of motor neuron precursor cells.These findings suggest that downregulation of the PI3K/Akt and MAP K/ERK signaling pathways leading to reduced cell proliferation and G0/G1 phase cell cycle arrest in induced pluripotent stem cells might be the underlying mechanism of the severe p.S87L SMA-like phenotype.p.S87L-ASO-targeting treatment can alleviate disordered cell proliferation in the early stage of pluripotent stem cell induction.展开更多
Two questions in the research of animal personality—whether there is a correlation between a personality trait and individual reproductive success,and what is the genetic basis underlying a personality trait—remain ...Two questions in the research of animal personality—whether there is a correlation between a personality trait and individual reproductive success,and what is the genetic basis underlying a personality trait—remain unresolved.We addressed these two questions in three shrub-nesting birds,the Azure-winged Magpie(Cyanopica cyanus,AM),White-collared Blackbird(Turdus albocinctus,WB),and Brown-cheeked Laughingthrush(Trochalopteron henrici,BL).The personality type of an individual was first identified according to its response to a territorial intruder.Then,we compared the fleeing distance,breeding parameters,and differential expressed genes(DEGs) in the brain transcriptome between bold and shy breeders.In the three species,bold breeders exhibited more aggressiveness towards an intruder of their territory than did shy breeders.The reproductive success of bold breeders was significantly higher than that of shy breeders in AM but not in WB and BL.The three species shared one DEG,crabp1,which was up-regulated in bold relative to in shy individuals.By regulating the expression of corticotropin-releasing hormone,higher crabp1 gene expression can decrease cellular response to retinoic acid.Therefore,bold individuals are insensitive to external stresses and able to exhibit more aggressiveness to intruders than their shier counterparts.Aggressiveness is beneficial to bold individuals in AM but not in WB and BL because the former could evoke neighbors to make the same response of defending against intruders but the latter could not.Although a personality trait may have the same genetic basis across species,its correlation with reproductive success depends largely on the life history style of a species.展开更多
Rechargeable Li-S batteries(LSBs)are emerging as an important alternative to lithium-ion batteries(LIBs),owing to their high energy densities and low cost;yet sluggish redox kinetics of LiPSs results in inferior cycle...Rechargeable Li-S batteries(LSBs)are emerging as an important alternative to lithium-ion batteries(LIBs),owing to their high energy densities and low cost;yet sluggish redox kinetics of LiPSs results in inferior cycle life.Herein,we prepared multifunctional self-supporting hyphae carbon nanobelt(HCNB)as hosts by carbonization of hyphae balls of Rhizopus,which could increase the S loading of the cathode without sacrificing reaction kinetics.Trace platinum(Pt)nanoparticles were introduced into HCNBs(PtHCNBs)by ion-beam sputtering deposition.Based on the X-ray photoelectron spectroscopy analyses,the introduced trace Pt regulated the local electronic states of heteroatoms in HCNBs.Electrochemical kinetics investigation combined with operando Raman measurements revealed the accelerated reaction mechanics of sulfur species.Benefiting from the synergistic catalytic effect and the unique structures,the as-prepared PtHCNB/MWNCT/S cathodes delivered a stable capacity retention of 77%for 400 cycles at 0.5 C with a sulfur loading of 4.6 mg cm^(-2).More importantly,remarkable cycling performance was achieved with an high areal S loading of 7.6 mg cm^(-2).This finding offers a new strategy to prolong the cycle life of LSBs.展开更多
In this editorial,we examine a paper by Koizumi et al,on the role of peroxisome proliferator-activated receptor(PPAR)agonists in alcoholic liver disease(ALD).The study determined whether elafibranor protected the inte...In this editorial,we examine a paper by Koizumi et al,on the role of peroxisome proliferator-activated receptor(PPAR)agonists in alcoholic liver disease(ALD).The study determined whether elafibranor protected the intestinal barrier and reduced liver fibrosis in a mouse model of ALD.The study also underlines the role of PPARs in intestinal barrier function and lipid homeostasis,which are both affected by ALD.Effective therapies are necessary for ALD because it is a critical health issue that affects people worldwide.This editorial analyzes the possibility of PPAR agonists as treatments for ALD.As key factors of inflammation and metabolism,PPARs offer multiple methods for managing the complex etiology of ALD.We assess the abilities of PPARα,PPARγ,and PPARβ/δagonists to prevent steatosis,inflammation,and fibrosis due to liver diseases.Recent research carried out in preclinical and clinical settings has shown that PPAR agonists can reduce the severity of liver disease.This editorial discusses the data analyzed and the obstacles,advantages,and mechanisms of action of PPAR agonists for ALD.Further research is needed to understand the efficacy,safety,and mechanisms of PPAR agonists for treating ALD.展开更多
Introduction:Among all malignant tumors of the digestive system,pancreatic carcinoma exhibits the highest mortality rate.Currently,prevention and effective treatment are urgent issues that need to be addressed.Methods...Introduction:Among all malignant tumors of the digestive system,pancreatic carcinoma exhibits the highest mortality rate.Currently,prevention and effective treatment are urgent issues that need to be addressed.Methods:The study focused on meiotic nuclear divisions 1(MND1),integrating data from the Gene Expression Profiling Interactive Analysis(GEPIA)database with prognostic survival analysis.Simultaneously,experiments at cellular level were employed to demonstrate the effect of MND1 on the proliferation and migration of PC.The small-molecule inhibitor of MND1 was used to suppress the migration of PC cells by knocking down MND1 using small interfering RNA(siRNA)in Patu-8988 and Panc1 cell lines.Results:The results of Cell Counting Kit-8 indicated that the suppression of MND1 resulted in a decrease in cell proliferation.Wound healing and Transwell assays revealed that MND1 knockdown reduced cell migration and invasion.Flow cytometry revealed that inhibiting MND1 hindered the cell cycle.Furthermore,MND1 could stimulate the proliferation,migration,and invasion of Patu-8988 and Panc1 cells by increasing the expression of MND1.Notably,MND1 had a positive effect on H2AFX expression in PC cells.Elevated MND1 expression suggests the low overall survival rate of individuals diagnosed with PC.Conclusion:These findings suggest that MND1 has the potential to be a gene with the ability to accurately diagnose and treat PC.展开更多
This study aims to investigate the protective effects of BlingLife®-berry extract on the eyes.BlingLife®-berry extract is a mixture of high-quality natural berries,including blackcurrant,aromia,bilberry and ...This study aims to investigate the protective effects of BlingLife®-berry extract on the eyes.BlingLife®-berry extract is a mixture of high-quality natural berries,including blackcurrant,aromia,bilberry and maquiberry.The main active ingredient responsible for theeye-protective effects is anthocyanins.Anthocyanins are natural water-soluble pigments belonging to the flavonoid class,and theyhave multiple benefits,including improving vision,anti-inflammatory and antibacterial properties,and antioxidant effects.Dueto the dual benefits of anthocyanins in protecting vision and eliminating free radicals,this study explores the comprehensive eye protective effects of BlingLife®-berry extract in terms of combating blue light-induced eye damage and oxidative stress-inducedvisual fatigue.The results provide robust evidence for the in vivo effects and further technological applications of BlingLife®-berry extract.展开更多
The Department of Biology at Peking University was established in 1925,with Mr.Tan Xi Hong as its inaugural department head.In 1993,the department was renamed the School of Life Sciences.During the past 90 years,a ste...The Department of Biology at Peking University was established in 1925,with Mr.Tan Xi Hong as its inaugural department head.In 1993,the department was renamed the School of Life Sciences.During the past 90 years,a steady stream of students has enrolled in the department in order to explore the secrets of life and to dedicate themselves to the advancement of society.展开更多
A growing body of evidence suggests that the gut microbiota contributes to the development of neurodegenerative diseases via the microbiota-gut-brain axis.As a contributing factor,microbiota dysbiosis always occurs in...A growing body of evidence suggests that the gut microbiota contributes to the development of neurodegenerative diseases via the microbiota-gut-brain axis.As a contributing factor,microbiota dysbiosis always occurs in pathological changes of neurodegenerative diseases,such as Alzheimer’s disease,Parkinson’s disease,and amyotrophic lateral sclerosis.High-throughput sequencing technology has helped to reveal that the bidirectional communication between the central nervous system and the enteric nervous system is facilitated by the microbiota’s diverse microorganisms,and for both neuroimmune and neuroendocrine systems.Here,we summarize the bioinformatics analysis and wet-biology validation for the gut metagenomics in neurodegenerative diseases,with an emphasis on multi-omics studies and the gut virome.The pathogen-associated signaling biomarkers for identifying brain disorders and potential therapeutic targets are also elucidated.Finally,we discuss the role of diet,prebiotics,probiotics,postbiotics and exercise interventions in remodeling the microbiome and reducing the symptoms of neurodegenerative diseases.展开更多
The study of modified RNA known as epitranscriptomics has become increasingly relevant in our understanding of disease-modifying mechanisms.Methylation of N6 adenosine(m^(6)A)and C5 cytosine(m^(5)C)bases occur on mRNA...The study of modified RNA known as epitranscriptomics has become increasingly relevant in our understanding of disease-modifying mechanisms.Methylation of N6 adenosine(m^(6)A)and C5 cytosine(m^(5)C)bases occur on mRNAs,tRNA,mt-tRNA,and rRNA species as well as non-coding RNAs.With emerging knowledge of RNA binding proteins that act as writer,reader,and eraser effector proteins,comes a new understanding of physiological processes controlled by these systems.Such processes when spatiotemporally disrupted within cellular nanodomains in highly specialized tissues such as the brain,give rise to different forms of disease.In this review,we discuss accumulating evidence that changes in the m^(6)A and m^(5)C methylation systems contribute to neurocognitive disorders.Early studies first identified mutations within FMR1 to cause intellectual disability Fragile X syndromes several years before FMR1 was identified as an m^(6)A RNA reader protein.Subsequently,familial mutations within the m^(6)A writer gene METTL5,m^(5)C writer genes NSUN2,NSUN3,NSUN5,and NSUN6,as well as THOC2 and THOC6 that form a protein complex with the m^(5)C reader protein ALYREF,were recognized to cause intellectual development disorders.Similarly,differences in expression of the m^(5)C writer and reader effector proteins,NSUN6,NSUN7,and ALYREF in brain tissue are indicated in individuals with Alzheimer's disease,individuals with a high neuropathological load or have suffered traumatic brain injury.Likewise,an abundance of m^(6)A reader and anti-reader proteins are reported to change across brain regions in Lewy bodies diseases,Alzheimer's disease,and individuals with high cognitive reserve.m^(6)A-modified RNAs are also reported significantly more abundant in dementia with Lewy bodies brain tissue but significantly reduced in Parkinson's disease tissue,whilst modified RNAs are misplaced within diseased cells,particularly where synapses are located.In parahippocampal brain tissue,m^(6)A modification is enriched in transcripts associated with psychiatric disorders including conditions with clear cognitive deficits.These findings indicate a diverse set of molecular mechanisms are influenced by RNA methylation systems that can cause neuronal and synaptic dysfunction underlying neurocognitive disorders.Targeting these RNA modification systems brings new prospects for neural regenerative therapies.展开更多
Injuries caused by trauma and neurodegenerative diseases can damage the peripheral nervous system and cause functional deficits.Unlike in the central nervous system,damaged axons in peripheral nerves can be induced to...Injuries caused by trauma and neurodegenerative diseases can damage the peripheral nervous system and cause functional deficits.Unlike in the central nervous system,damaged axons in peripheral nerves can be induced to regenerate in response to intrinsic cues after reprogramming or in a growth-promoting microenvironment created by Schwann cells.However,axon regeneration and repair do not automatically result in the restoration of function,which is the ultimate therapeutic goal but also a major clinical challenge.Transforming growth factor(TGF)is a multifunctional cytokine that regulates various biological processes including tissue repair,embryo development,and cell growth and differentiation.There is accumulating evidence that TGF-βfamily proteins participate in peripheral nerve repair through various factors and signaling pathways by regulating the growth and transformation of Schwann cells;recruiting specific immune cells;controlling the permeability of the blood-nerve barrier,thereby stimulating axon growth;and inhibiting remyelination of regenerated axons.TGF-βhas been applied to the treatment of peripheral nerve injury in animal models.In this context,we review the functions of TGF-βin peripheral nerve regeneration and potential clinical applications.展开更多
Sortilin-related receptor 1(SORL1)is a critical gene associated with late-onset Alzheimer’s disease.SORL1 contributes to the development and progression of this neurodegenerative condition by affecting the transport ...Sortilin-related receptor 1(SORL1)is a critical gene associated with late-onset Alzheimer’s disease.SORL1 contributes to the development and progression of this neurodegenerative condition by affecting the transport and metabolism of intracellularβ-amyloid precursor protein.To better understand the underlying mechanisms of SORL1 in the pathogenesis of late-onset Alzheimer s disease,in this study,we established a mouse model of SorI1 gene knockout using cluste red regularly inters paced short palindro mic repeats-associated protein 9 technology.We found that Sorl1-knocko ut mice displayed deficits in learning and memory.Furthermore,the expression of brain-derived neurotrophic factor was significantly downregulated in the hippocampus and co rtex,and amyloidβ-protein deposits were observed in the brains of 5orl1-knockout mice.In vitro,hippocampal neuronal cell synapses from homozygous Sorl1-knockout mice were impaired.The expression of synaptic proteins,including Drebrin and NR2B,was significantly reduced,and also their colocalization.Additionally,by knocking out the Sorl1 gene in N2a cells,we found that expression of the N-methyl-D-aspartate receptor,NR2B,and cyclic adenosine monophosphate-response element binding protein was also inhibited.These findings suggest that SORL1 participates in the pathogenesis of late-onset Alzheimer s disease by regulating the N-methyl-D-aspartate receptor NR2B/cyclic adenosine monophosphate-response element binding protein signaling axis.展开更多
Cellular senescence and chronic inflammation in response to aging are considered to be indicators of brain aging;they have a great impact on the aging process and are the main risk factors for neurodegeneration.Review...Cellular senescence and chronic inflammation in response to aging are considered to be indicators of brain aging;they have a great impact on the aging process and are the main risk factors for neurodegeneration.Reviewing the microglial response to aging and neuroinflammation in neurodegenerative diseases will help understand the importance of microglia in neurodegenerative diseases.This review describes the origin and function of microglia and focuses on the role of different states of the microglial response to aging and chronic inflammation on the occurrence and development of neurodegenerative diseases,including Alzheimer's disease,Huntington's chorea,and Parkinson's disease.This review also describes the potential benefits of treating neurodegenerative diseases by modulating changes in microglial states.Therefore,inducing a shift from the neurotoxic to neuroprotective microglial state in neurodegenerative diseases induced by aging and chronic inflammation holds promise for the treatment of neurodegenerative diseases in the future.展开更多
Glutamatergic projection neurons generate sophisticated excitatory circuits to integrate and transmit information among different cortical areas,and between the neocortex and other regions of the brain and spinal cord...Glutamatergic projection neurons generate sophisticated excitatory circuits to integrate and transmit information among different cortical areas,and between the neocortex and other regions of the brain and spinal cord.Appropriate development of cortical projection neurons is regulated by certain essential events such as neural fate determination,proliferation,specification,differentiation,migration,survival,axonogenesis,and synaptogenesis.These processes are precisely regulated in a tempo-spatial manner by intrinsic factors,extrinsic signals,and neural activities.The generation of correct subtypes and precise connections of projection neurons is imperative not only to support the basic cortical functions(such as sensory information integration,motor coordination,and cognition)but also to prevent the onset and progression of neurodevelopmental disorders(such as intellectual disability,autism spectrum disorders,anxiety,and depression).This review mainly focuses on the recent progress of transcriptional regulations on the development and diversity of neocortical projection neurons and the clinical relevance of the failure of transcriptional modulations.展开更多
BACKGROUND Currently,traditional Chinese medicine(TCM)formulas are commonly being used as adjunctive therapy for ulcerative colitis in China.Network meta-analysis,a quantitative and comprehensive analytical method,can...BACKGROUND Currently,traditional Chinese medicine(TCM)formulas are commonly being used as adjunctive therapy for ulcerative colitis in China.Network meta-analysis,a quantitative and comprehensive analytical method,can systematically compare the effects of different adjunctive treatment options for ulcerative colitis,providing scientific evidence for clinical decision-making.AIM To evaluate the clinical efficacy and safety of commonly used TCM for the treatment of ulcerative colitis(UC)in clinical practice through a network metaanalysis.METHODS Clinical randomized controlled trials of these TCM formulas used for the adjuvant treatment of UC were searched from the establishment of the databases to July 1,2022.Studies that met the inclusion criteria were screened and evaluated for literature quality and risk of bias according to the Cochrane 5.1 standard.The methodological quality of the studies was assessed using ReviewManager(RevMan)5.4,and a funnel plot was constructed to test for publication bias.ADDIS 1.16 statistical software was used to perform statistical analysis of the treatment measures and derive the network relationship and ranking diagrams of the various intervention measures.RESULTS A total of 64 randomized controlled trials involving 5456 patients with UC were included in this study.The adjuvant treatment of UC using five TCM formulations was able to improve the clinical outcome of the patients.Adjuvant treatment with Baitouweng decoction(BTWT)showed a significant effect[mean difference=36.22,95%confidence interval(CI):7.63 to 65.76].For the reduction of tumor necrosis factor in patients with UC,adjunctive therapy with BTWT(mean difference=−9.55,95%CI:−17.89 to−1.41),Shenlingbaizhu powder[SLBZS;odds ratio(OR)=0.19,95%CI:0.08 to 0.39],and Shaoyao decoction(OR=−23.02,95%CI:−33.64 to−13.14)was effective.Shaoyao decoction was more effective than BTWT(OR=0.12,95%CI:0.03 to 0.39),SLBZS(OR=0.19,95%CI:0.08 to 0.39),and Xi Lei powder(OR=0.34,95%CI:0.13 to 0.81)in reducing tumor necrosis factor and the recurrence rate of UC.CONCLUSION TCM combined with mesalazine is more effective than mesalazine alone in the treatment of UC.展开更多
Tibetan singing bowls emit low-frequency sounds and produce perceptible harmonic tones and vibrations through manual tapping.The sounds the singing bowls produce have been shown to enhance relaxation and reduce anxiet...Tibetan singing bowls emit low-frequency sounds and produce perceptible harmonic tones and vibrations through manual tapping.The sounds the singing bowls produce have been shown to enhance relaxation and reduce anxiety.However,the underlying mechanism remains unclear.In this study,we used chronic restraint stress or sleep deprivation to establish mouse models of anxiety that exhibit anxiety-like behaviors.We then supplied treatment with singing bowls in a bottomless cage placed on the top of a cushion.We found that unlike in humans,the combination of harmonic tones and vibrations did not improve anxietylike behaviors in mice,while individual vibration components did.Additionally,the vibration of singing bowls increased the level of N-methyl-D-aspartate receptor 1 in the somatosensory cortex and prefrontal cortex of the mice,decreased the level ofγ-aminobutyric acid A(GABA)receptorα1 subtype,reduced the level of CaMKII in the prefrontal cortex,and increased the number of GABAergic interneurons.At the same time,electrophysiological tests showed that the vibration of singing bowls significantly reduced the abnormal low-frequency gamma oscillation peak frequency in the medial prefrontal cortex caused by stress restraint pressure and sleep deprivation.Results from this study indicate that the vibration of singing bowls can alleviate anxiety-like behaviors by reducing abnormal molecular and electrophysiological events in somatosensory and medial prefrontal cortex.展开更多
General anesthesia is widely applied in clinical practice.However,the precise mechanism of loss of consciousness induced by general anesthetics remains unknown.Here,we measured the dynamics of five neurotransmitters,i...General anesthesia is widely applied in clinical practice.However,the precise mechanism of loss of consciousness induced by general anesthetics remains unknown.Here,we measured the dynamics of five neurotransmitters,includingγ-aminobutyric acid,glutamate,norepinephrine,acetylcholine,and dopamine,in the medial prefrontal cortex and primary visual cortex of C57BL/6 mice through in vivo fiber photometry and genetically encoded neurotransmitter sensors under anesthesia to reveal the mechanism of general anesthesia from a neurotransmitter perspective.Results revealed that the concentrations of γ-aminobutyric acid,glutamate,norepinephrine,and acetylcholine increased in the cortex during propofol-induced loss of consciousness.Dopamine levels did not change following the hypnotic dose of propofol but increased significantly following surgical doses of propofol anesthesia.Notably,the concentrations of the five neurotransmitters generally decreased during sevoflurane-induced loss of consciousness.Furthermore,the neurotransmitter dynamic networks were not synchronized in the non-anesthesia groups but were highly synchronized in the anesthetic groups.These findings suggest that neurotransmitter dynamic network synchronization may cause anesthetic-induced loss of consciousness.展开更多
α-Glucosidase inhibitors are effective in controlling postprandial hyperglycemia,which play crucial roles in the management of type 2 diabetes.Protocatechuic acid(PCA)is one of phenolic acids existing not only in var...α-Glucosidase inhibitors are effective in controlling postprandial hyperglycemia,which play crucial roles in the management of type 2 diabetes.Protocatechuic acid(PCA)is one of phenolic acids existing not only in various plant foods but also as a major microbial metabolite of dietary anthocyanins in the large colon.The present study investigated the inhibitory mechanism of PCA on a-glucosidase in vitro and examined its effect on postprandial blood glucose levels in vivo.Results from in vitro experiments demonstrated that PCA was a mix-type inhibitor of a-glucosidase.Driven by hydrogen bonds and van der Waals interactions,PCA reversibly bound withα-glucosidase to form a stable a-glucosidase-PCA complex in a spontaneous manner.The computational simulation found that PCA could insert into the active cavity of a-glucosidase and establish hydrogen bonds with catalytic amino acid residues.PCA binding aroused the steric hindrance for substrates to enter active sites and caused the structural changes of interacted catalytic amino acid residues.PCA also exhibited postprandial hypoglycemic capacity in diabetic mice.This study may provide the theoretical basis for the application of PCA as an active ingredient of functional foods in dietary management of diabetes.展开更多
Plant-mediated RNA interference(RNAi)has emerged as a promising technology for insect control.The green peach aphid,Myzus persicae,feeds on over 400 species of host plants.Brassica napus(rape)is the second most import...Plant-mediated RNA interference(RNAi)has emerged as a promising technology for insect control.The green peach aphid,Myzus persicae,feeds on over 400 species of host plants.Brassica napus(rape)is the second most important oilseed crop worldwide.Myzus persicae is highly reproductive and causes severe damage to the rape plants due to its quite flexible life cycle.In this study,we tested the RNAi effects of transgenic rape plants on M.persicae.By in vitro feeding M.persicae with artificial diets containing double-stranded RNAs(dsRNAs)targeting seven aphid genes,we identified a new gene encoding the partitioning-defective protein 6(Par6)as the most potent RNAi target.Tissue-and stage-expression analysis of Par6 suggested this gene is highly expressed in the embryo and adult stage of M.persicae.We next generated transgenic rape plants expressing ds Par6 by Agrobacteriummediated transformation and obtained nine independent transgenic lines.Compared to wild-type control plants,transgenic rape lines expressing ds Par6 showed strong resistance to M.persicae.Feeding assays revealed that feeding transgenic rape plants to M.persicae significantly decreased MpPar6 expression and survival rate and impaired fecundity.Furthermore,we showed that the resistance levels to M.persicae are positively correlated with ds Par6 expression levels in transgenic rape plants.Our study demonstrates that transgenic rape plants expressing ds Par6 are efficiently protected from M.persicae.Interfering with the genes involved in embryo development could be the effective RNAi targets for controlling aphids and potentially other insect pests.展开更多
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
Anti-tumor angiogenesis therapy, targeting the suppression of blood vessel growth in tumors, presents a potent approach in the battle against cancer. Traditional therapies have primarily concentrated on single-target ...Anti-tumor angiogenesis therapy, targeting the suppression of blood vessel growth in tumors, presents a potent approach in the battle against cancer. Traditional therapies have primarily concentrated on single-target techniques, with a specific emphasis on targeting the vascular endothelial growth factor, but have not reached ideal therapeutic efficacy. In response to this issue, our study introduced a novel nanoparticle system known as CS-siRNA/PEITC&L-cRGD NPs. These chitosan-based nanoparticles have been recognized for their excellent biocompatibility and ability to deliver genes. To enhance their targeted delivery capability, they were combined with a cyclic RGD peptide (cRGD). Targeted co-delivery of gene and chemotherapeutic agents was achieved through the use of a negatively charged lipid shell and cRGD, which possesses high affinity for integrin αvβ3 overexpressed in tumor cells and neovasculature. In this multifaceted approach, co-delivery of VEGF siRNA and phenethyl isothiocyanate (PEITC) was employed to target both tumor vascular endothelial cells and tumor cells simultaneously. The co-delivery of VEGF siRNA and PEITC could achieve precise silencing of VEGF, inhibit the accumulation of HIF-1α under hypoxic conditions, and induce apoptosis in tumor cells. In summary, we have successfully developed a nanoparticle delivery platform that utilizes a dual mechanism of action of anti-tumor angiogenesis and pro-tumor apoptosis, which provides a robust and potent strategy for the delivery of anti-cancer therapeutics.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82171172(to RZ)and 81771366(to RZ)Fundamental Research Funds for the Central Universities of Central South University,Nos.2021zzts1095(to SZ)and 2022zzts0832(to HY)。
文摘Mutations in the microrchidia CW-type zinc finger protein 2(MORC2)gene are the causative agent of Charcot-Marie-Tooth disease type 2Z(CMT2Z),and the hotspot mutation p.S87L is associated with a more seve re spinal muscular atrophy-like clinical phenotype.The aims of this study were to determine the mechanism of the severe phenotype caused by the MORC2 p.S87L mutation and to explore potential treatment strategies.Epithelial cells were isolated from urine samples from a spinal muscular atrophy(SMA)-like patient[MORC2 p.S87L),a CMT2Z patient[MORC2 p.Q400R),and a healthy control and induced to generate pluripotent stem cells,which were then differentiated into motor neuron precursor cells.Next-generation RNA sequencing followed by KEGG pathway enrichment analysis revealed that differentially expressed genes involved in the PI3K/Akt and MAP K/ERK signaling pathways were enriched in the p.S87L SMA-like patient group and were significantly downregulated in induced pluripotent stem cells.Reduced proliferation was observed in the induced pluripotent stem cells and motor neuron precursor cells derived from the p.S87L SMA-like patient group compared with the CMT2Z patient group and the healthy control.G0/G1 phase cell cycle arrest was observed in induced pluripotent stem cells derived from the p.S87L SMA-like patient.MORC2 p.S87Lspecific antisense oligonucleotides(p.S87L-ASO-targeting)showed significant efficacy in improving cell prolife ration and activating the PI3K/Akt and MAP K/ERK pathways in induced pluripotent stem cells.Howeve r,p.S87L-ASO-ta rgeting did not rescue prolife ration of motor neuron precursor cells.These findings suggest that downregulation of the PI3K/Akt and MAP K/ERK signaling pathways leading to reduced cell proliferation and G0/G1 phase cell cycle arrest in induced pluripotent stem cells might be the underlying mechanism of the severe p.S87L SMA-like phenotype.p.S87L-ASO-targeting treatment can alleviate disordered cell proliferation in the early stage of pluripotent stem cell induction.
基金provided by the National Natural Science Foundation of China (Grant 32071491, 31772465, 31672299, 31572271, and 32260128)the Natural Sciences Foundation of the Tibetan (XZ202101ZR0051G)。
文摘Two questions in the research of animal personality—whether there is a correlation between a personality trait and individual reproductive success,and what is the genetic basis underlying a personality trait—remain unresolved.We addressed these two questions in three shrub-nesting birds,the Azure-winged Magpie(Cyanopica cyanus,AM),White-collared Blackbird(Turdus albocinctus,WB),and Brown-cheeked Laughingthrush(Trochalopteron henrici,BL).The personality type of an individual was first identified according to its response to a territorial intruder.Then,we compared the fleeing distance,breeding parameters,and differential expressed genes(DEGs) in the brain transcriptome between bold and shy breeders.In the three species,bold breeders exhibited more aggressiveness towards an intruder of their territory than did shy breeders.The reproductive success of bold breeders was significantly higher than that of shy breeders in AM but not in WB and BL.The three species shared one DEG,crabp1,which was up-regulated in bold relative to in shy individuals.By regulating the expression of corticotropin-releasing hormone,higher crabp1 gene expression can decrease cellular response to retinoic acid.Therefore,bold individuals are insensitive to external stresses and able to exhibit more aggressiveness to intruders than their shier counterparts.Aggressiveness is beneficial to bold individuals in AM but not in WB and BL because the former could evoke neighbors to make the same response of defending against intruders but the latter could not.Although a personality trait may have the same genetic basis across species,its correlation with reproductive success depends largely on the life history style of a species.
基金partially supported by grants from the National Natural Science Foundation of China(52072099)Team program of the Natural Science Foundation of Heilongjiang Province,China(No.TD2021E005)
文摘Rechargeable Li-S batteries(LSBs)are emerging as an important alternative to lithium-ion batteries(LIBs),owing to their high energy densities and low cost;yet sluggish redox kinetics of LiPSs results in inferior cycle life.Herein,we prepared multifunctional self-supporting hyphae carbon nanobelt(HCNB)as hosts by carbonization of hyphae balls of Rhizopus,which could increase the S loading of the cathode without sacrificing reaction kinetics.Trace platinum(Pt)nanoparticles were introduced into HCNBs(PtHCNBs)by ion-beam sputtering deposition.Based on the X-ray photoelectron spectroscopy analyses,the introduced trace Pt regulated the local electronic states of heteroatoms in HCNBs.Electrochemical kinetics investigation combined with operando Raman measurements revealed the accelerated reaction mechanics of sulfur species.Benefiting from the synergistic catalytic effect and the unique structures,the as-prepared PtHCNB/MWNCT/S cathodes delivered a stable capacity retention of 77%for 400 cycles at 0.5 C with a sulfur loading of 4.6 mg cm^(-2).More importantly,remarkable cycling performance was achieved with an high areal S loading of 7.6 mg cm^(-2).This finding offers a new strategy to prolong the cycle life of LSBs.
文摘In this editorial,we examine a paper by Koizumi et al,on the role of peroxisome proliferator-activated receptor(PPAR)agonists in alcoholic liver disease(ALD).The study determined whether elafibranor protected the intestinal barrier and reduced liver fibrosis in a mouse model of ALD.The study also underlines the role of PPARs in intestinal barrier function and lipid homeostasis,which are both affected by ALD.Effective therapies are necessary for ALD because it is a critical health issue that affects people worldwide.This editorial analyzes the possibility of PPAR agonists as treatments for ALD.As key factors of inflammation and metabolism,PPARs offer multiple methods for managing the complex etiology of ALD.We assess the abilities of PPARα,PPARγ,and PPARβ/δagonists to prevent steatosis,inflammation,and fibrosis due to liver diseases.Recent research carried out in preclinical and clinical settings has shown that PPAR agonists can reduce the severity of liver disease.This editorial discusses the data analyzed and the obstacles,advantages,and mechanisms of action of PPAR agonists for ALD.Further research is needed to understand the efficacy,safety,and mechanisms of PPAR agonists for treating ALD.
基金supported by grants from National Innovation Program for College Students(202210367076)Graduate Student Research Innovation Program of Bengbu Medical College(Byycxz22016)the National Natural Science Foundation of China(82072585),and the Key Research Project of Bengbu Medical College(No.2020byzd029).
文摘Introduction:Among all malignant tumors of the digestive system,pancreatic carcinoma exhibits the highest mortality rate.Currently,prevention and effective treatment are urgent issues that need to be addressed.Methods:The study focused on meiotic nuclear divisions 1(MND1),integrating data from the Gene Expression Profiling Interactive Analysis(GEPIA)database with prognostic survival analysis.Simultaneously,experiments at cellular level were employed to demonstrate the effect of MND1 on the proliferation and migration of PC.The small-molecule inhibitor of MND1 was used to suppress the migration of PC cells by knocking down MND1 using small interfering RNA(siRNA)in Patu-8988 and Panc1 cell lines.Results:The results of Cell Counting Kit-8 indicated that the suppression of MND1 resulted in a decrease in cell proliferation.Wound healing and Transwell assays revealed that MND1 knockdown reduced cell migration and invasion.Flow cytometry revealed that inhibiting MND1 hindered the cell cycle.Furthermore,MND1 could stimulate the proliferation,migration,and invasion of Patu-8988 and Panc1 cells by increasing the expression of MND1.Notably,MND1 had a positive effect on H2AFX expression in PC cells.Elevated MND1 expression suggests the low overall survival rate of individuals diagnosed with PC.Conclusion:These findings suggest that MND1 has the potential to be a gene with the ability to accurately diagnose and treat PC.
文摘This study aims to investigate the protective effects of BlingLife®-berry extract on the eyes.BlingLife®-berry extract is a mixture of high-quality natural berries,including blackcurrant,aromia,bilberry and maquiberry.The main active ingredient responsible for theeye-protective effects is anthocyanins.Anthocyanins are natural water-soluble pigments belonging to the flavonoid class,and theyhave multiple benefits,including improving vision,anti-inflammatory and antibacterial properties,and antioxidant effects.Dueto the dual benefits of anthocyanins in protecting vision and eliminating free radicals,this study explores the comprehensive eye protective effects of BlingLife®-berry extract in terms of combating blue light-induced eye damage and oxidative stress-inducedvisual fatigue.The results provide robust evidence for the in vivo effects and further technological applications of BlingLife®-berry extract.
文摘The Department of Biology at Peking University was established in 1925,with Mr.Tan Xi Hong as its inaugural department head.In 1993,the department was renamed the School of Life Sciences.During the past 90 years,a steady stream of students has enrolled in the department in order to explore the secrets of life and to dedicate themselves to the advancement of society.
基金financially supported by the National Natural Science Foundation of China,No.32002235(to MT)the Science and Technology Foundation of Taian of Shandong Province,No.2020NS216(to XL)。
文摘A growing body of evidence suggests that the gut microbiota contributes to the development of neurodegenerative diseases via the microbiota-gut-brain axis.As a contributing factor,microbiota dysbiosis always occurs in pathological changes of neurodegenerative diseases,such as Alzheimer’s disease,Parkinson’s disease,and amyotrophic lateral sclerosis.High-throughput sequencing technology has helped to reveal that the bidirectional communication between the central nervous system and the enteric nervous system is facilitated by the microbiota’s diverse microorganisms,and for both neuroimmune and neuroendocrine systems.Here,we summarize the bioinformatics analysis and wet-biology validation for the gut metagenomics in neurodegenerative diseases,with an emphasis on multi-omics studies and the gut virome.The pathogen-associated signaling biomarkers for identifying brain disorders and potential therapeutic targets are also elucidated.Finally,we discuss the role of diet,prebiotics,probiotics,postbiotics and exercise interventions in remodeling the microbiome and reducing the symptoms of neurodegenerative diseases.
基金funded by Notingham University and the Neuroscience Support Group Charity,UK(to HMK)supported by a CONACYT PhD scholarshipMD?was supported by the Postdoctoral Research Fellowship Program of TUBITAK。
文摘The study of modified RNA known as epitranscriptomics has become increasingly relevant in our understanding of disease-modifying mechanisms.Methylation of N6 adenosine(m^(6)A)and C5 cytosine(m^(5)C)bases occur on mRNAs,tRNA,mt-tRNA,and rRNA species as well as non-coding RNAs.With emerging knowledge of RNA binding proteins that act as writer,reader,and eraser effector proteins,comes a new understanding of physiological processes controlled by these systems.Such processes when spatiotemporally disrupted within cellular nanodomains in highly specialized tissues such as the brain,give rise to different forms of disease.In this review,we discuss accumulating evidence that changes in the m^(6)A and m^(5)C methylation systems contribute to neurocognitive disorders.Early studies first identified mutations within FMR1 to cause intellectual disability Fragile X syndromes several years before FMR1 was identified as an m^(6)A RNA reader protein.Subsequently,familial mutations within the m^(6)A writer gene METTL5,m^(5)C writer genes NSUN2,NSUN3,NSUN5,and NSUN6,as well as THOC2 and THOC6 that form a protein complex with the m^(5)C reader protein ALYREF,were recognized to cause intellectual development disorders.Similarly,differences in expression of the m^(5)C writer and reader effector proteins,NSUN6,NSUN7,and ALYREF in brain tissue are indicated in individuals with Alzheimer's disease,individuals with a high neuropathological load or have suffered traumatic brain injury.Likewise,an abundance of m^(6)A reader and anti-reader proteins are reported to change across brain regions in Lewy bodies diseases,Alzheimer's disease,and individuals with high cognitive reserve.m^(6)A-modified RNAs are also reported significantly more abundant in dementia with Lewy bodies brain tissue but significantly reduced in Parkinson's disease tissue,whilst modified RNAs are misplaced within diseased cells,particularly where synapses are located.In parahippocampal brain tissue,m^(6)A modification is enriched in transcripts associated with psychiatric disorders including conditions with clear cognitive deficits.These findings indicate a diverse set of molecular mechanisms are influenced by RNA methylation systems that can cause neuronal and synaptic dysfunction underlying neurocognitive disorders.Targeting these RNA modification systems brings new prospects for neural regenerative therapies.
基金supported by the National Natural Science Foundation of China,Nos.31971277 and 31950410551(both to DY)。
文摘Injuries caused by trauma and neurodegenerative diseases can damage the peripheral nervous system and cause functional deficits.Unlike in the central nervous system,damaged axons in peripheral nerves can be induced to regenerate in response to intrinsic cues after reprogramming or in a growth-promoting microenvironment created by Schwann cells.However,axon regeneration and repair do not automatically result in the restoration of function,which is the ultimate therapeutic goal but also a major clinical challenge.Transforming growth factor(TGF)is a multifunctional cytokine that regulates various biological processes including tissue repair,embryo development,and cell growth and differentiation.There is accumulating evidence that TGF-βfamily proteins participate in peripheral nerve repair through various factors and signaling pathways by regulating the growth and transformation of Schwann cells;recruiting specific immune cells;controlling the permeability of the blood-nerve barrier,thereby stimulating axon growth;and inhibiting remyelination of regenerated axons.TGF-βhas been applied to the treatment of peripheral nerve injury in animal models.In this context,we review the functions of TGF-βin peripheral nerve regeneration and potential clinical applications.
基金supported by the Community Development Office of Hunan Provincial Science and Technology DepartmentChina,Nos.2020SK53613(to DH),21JJ31006(to DH)the Fundamental Research Funds of Central South University,Nos.CX20220375(to TX),2023zzts215(to MZ)。
文摘Sortilin-related receptor 1(SORL1)is a critical gene associated with late-onset Alzheimer’s disease.SORL1 contributes to the development and progression of this neurodegenerative condition by affecting the transport and metabolism of intracellularβ-amyloid precursor protein.To better understand the underlying mechanisms of SORL1 in the pathogenesis of late-onset Alzheimer s disease,in this study,we established a mouse model of SorI1 gene knockout using cluste red regularly inters paced short palindro mic repeats-associated protein 9 technology.We found that Sorl1-knocko ut mice displayed deficits in learning and memory.Furthermore,the expression of brain-derived neurotrophic factor was significantly downregulated in the hippocampus and co rtex,and amyloidβ-protein deposits were observed in the brains of 5orl1-knockout mice.In vitro,hippocampal neuronal cell synapses from homozygous Sorl1-knockout mice were impaired.The expression of synaptic proteins,including Drebrin and NR2B,was significantly reduced,and also their colocalization.Additionally,by knocking out the Sorl1 gene in N2a cells,we found that expression of the N-methyl-D-aspartate receptor,NR2B,and cyclic adenosine monophosphate-response element binding protein was also inhibited.These findings suggest that SORL1 participates in the pathogenesis of late-onset Alzheimer s disease by regulating the N-methyl-D-aspartate receptor NR2B/cyclic adenosine monophosphate-response element binding protein signaling axis.
基金supported partly by the National Natural Science Foundation of China,Nos.32161143021 and 81271410the Natural Science Foundation of Henan Province of China,No.182300410313(all to JW)。
文摘Cellular senescence and chronic inflammation in response to aging are considered to be indicators of brain aging;they have a great impact on the aging process and are the main risk factors for neurodegeneration.Reviewing the microglial response to aging and neuroinflammation in neurodegenerative diseases will help understand the importance of microglia in neurodegenerative diseases.This review describes the origin and function of microglia and focuses on the role of different states of the microglial response to aging and chronic inflammation on the occurrence and development of neurodegenerative diseases,including Alzheimer's disease,Huntington's chorea,and Parkinson's disease.This review also describes the potential benefits of treating neurodegenerative diseases by modulating changes in microglial states.Therefore,inducing a shift from the neurotoxic to neuroprotective microglial state in neurodegenerative diseases induced by aging and chronic inflammation holds promise for the treatment of neurodegenerative diseases in the future.
基金supported by Guangdong Provincial Basic and Applied Basic Research Fund,No.2021A1515011299(to KT)。
文摘Glutamatergic projection neurons generate sophisticated excitatory circuits to integrate and transmit information among different cortical areas,and between the neocortex and other regions of the brain and spinal cord.Appropriate development of cortical projection neurons is regulated by certain essential events such as neural fate determination,proliferation,specification,differentiation,migration,survival,axonogenesis,and synaptogenesis.These processes are precisely regulated in a tempo-spatial manner by intrinsic factors,extrinsic signals,and neural activities.The generation of correct subtypes and precise connections of projection neurons is imperative not only to support the basic cortical functions(such as sensory information integration,motor coordination,and cognition)but also to prevent the onset and progression of neurodevelopmental disorders(such as intellectual disability,autism spectrum disorders,anxiety,and depression).This review mainly focuses on the recent progress of transcriptional regulations on the development and diversity of neocortical projection neurons and the clinical relevance of the failure of transcriptional modulations.
文摘BACKGROUND Currently,traditional Chinese medicine(TCM)formulas are commonly being used as adjunctive therapy for ulcerative colitis in China.Network meta-analysis,a quantitative and comprehensive analytical method,can systematically compare the effects of different adjunctive treatment options for ulcerative colitis,providing scientific evidence for clinical decision-making.AIM To evaluate the clinical efficacy and safety of commonly used TCM for the treatment of ulcerative colitis(UC)in clinical practice through a network metaanalysis.METHODS Clinical randomized controlled trials of these TCM formulas used for the adjuvant treatment of UC were searched from the establishment of the databases to July 1,2022.Studies that met the inclusion criteria were screened and evaluated for literature quality and risk of bias according to the Cochrane 5.1 standard.The methodological quality of the studies was assessed using ReviewManager(RevMan)5.4,and a funnel plot was constructed to test for publication bias.ADDIS 1.16 statistical software was used to perform statistical analysis of the treatment measures and derive the network relationship and ranking diagrams of the various intervention measures.RESULTS A total of 64 randomized controlled trials involving 5456 patients with UC were included in this study.The adjuvant treatment of UC using five TCM formulations was able to improve the clinical outcome of the patients.Adjuvant treatment with Baitouweng decoction(BTWT)showed a significant effect[mean difference=36.22,95%confidence interval(CI):7.63 to 65.76].For the reduction of tumor necrosis factor in patients with UC,adjunctive therapy with BTWT(mean difference=−9.55,95%CI:−17.89 to−1.41),Shenlingbaizhu powder[SLBZS;odds ratio(OR)=0.19,95%CI:0.08 to 0.39],and Shaoyao decoction(OR=−23.02,95%CI:−33.64 to−13.14)was effective.Shaoyao decoction was more effective than BTWT(OR=0.12,95%CI:0.03 to 0.39),SLBZS(OR=0.19,95%CI:0.08 to 0.39),and Xi Lei powder(OR=0.34,95%CI:0.13 to 0.81)in reducing tumor necrosis factor and the recurrence rate of UC.CONCLUSION TCM combined with mesalazine is more effective than mesalazine alone in the treatment of UC.
基金supported by the National Natural Science Foundation of ChinaNos.32170950(to LY),31970915(to LY),31871170(to CL)+4 种基金the Natural Science Foundation of Guangdong Province for Major Cultivation ProjectNo.2018B030336001(to LY)the Natural Science Foundation of Guangdong Province,Nos.2021A1515010804(to CL),2023A1515010899(to CL)the Guangdong Grant‘Key Technologies for Treatment of Brain Disorders’No.2018B030332001(to CL)。
文摘Tibetan singing bowls emit low-frequency sounds and produce perceptible harmonic tones and vibrations through manual tapping.The sounds the singing bowls produce have been shown to enhance relaxation and reduce anxiety.However,the underlying mechanism remains unclear.In this study,we used chronic restraint stress or sleep deprivation to establish mouse models of anxiety that exhibit anxiety-like behaviors.We then supplied treatment with singing bowls in a bottomless cage placed on the top of a cushion.We found that unlike in humans,the combination of harmonic tones and vibrations did not improve anxietylike behaviors in mice,while individual vibration components did.Additionally,the vibration of singing bowls increased the level of N-methyl-D-aspartate receptor 1 in the somatosensory cortex and prefrontal cortex of the mice,decreased the level ofγ-aminobutyric acid A(GABA)receptorα1 subtype,reduced the level of CaMKII in the prefrontal cortex,and increased the number of GABAergic interneurons.At the same time,electrophysiological tests showed that the vibration of singing bowls significantly reduced the abnormal low-frequency gamma oscillation peak frequency in the medial prefrontal cortex caused by stress restraint pressure and sleep deprivation.Results from this study indicate that the vibration of singing bowls can alleviate anxiety-like behaviors by reducing abnormal molecular and electrophysiological events in somatosensory and medial prefrontal cortex.
基金supported by the National Natural Science Foundation of China(81870841 and 82171192 to X.S.L.,82101349 to G.L.Q.)。
文摘General anesthesia is widely applied in clinical practice.However,the precise mechanism of loss of consciousness induced by general anesthetics remains unknown.Here,we measured the dynamics of five neurotransmitters,includingγ-aminobutyric acid,glutamate,norepinephrine,acetylcholine,and dopamine,in the medial prefrontal cortex and primary visual cortex of C57BL/6 mice through in vivo fiber photometry and genetically encoded neurotransmitter sensors under anesthesia to reveal the mechanism of general anesthesia from a neurotransmitter perspective.Results revealed that the concentrations of γ-aminobutyric acid,glutamate,norepinephrine,and acetylcholine increased in the cortex during propofol-induced loss of consciousness.Dopamine levels did not change following the hypnotic dose of propofol but increased significantly following surgical doses of propofol anesthesia.Notably,the concentrations of the five neurotransmitters generally decreased during sevoflurane-induced loss of consciousness.Furthermore,the neurotransmitter dynamic networks were not synchronized in the non-anesthesia groups but were highly synchronized in the anesthetic groups.These findings suggest that neurotransmitter dynamic network synchronization may cause anesthetic-induced loss of consciousness.
基金supported by the General Research Fund of Hong Kong (14105820)。
文摘α-Glucosidase inhibitors are effective in controlling postprandial hyperglycemia,which play crucial roles in the management of type 2 diabetes.Protocatechuic acid(PCA)is one of phenolic acids existing not only in various plant foods but also as a major microbial metabolite of dietary anthocyanins in the large colon.The present study investigated the inhibitory mechanism of PCA on a-glucosidase in vitro and examined its effect on postprandial blood glucose levels in vivo.Results from in vitro experiments demonstrated that PCA was a mix-type inhibitor of a-glucosidase.Driven by hydrogen bonds and van der Waals interactions,PCA reversibly bound withα-glucosidase to form a stable a-glucosidase-PCA complex in a spontaneous manner.The computational simulation found that PCA could insert into the active cavity of a-glucosidase and establish hydrogen bonds with catalytic amino acid residues.PCA binding aroused the steric hindrance for substrates to enter active sites and caused the structural changes of interacted catalytic amino acid residues.PCA also exhibited postprandial hypoglycemic capacity in diabetic mice.This study may provide the theoretical basis for the application of PCA as an active ingredient of functional foods in dietary management of diabetes.
基金supported by the National Natural Science Foundation of China(32102297 and 32272634)。
文摘Plant-mediated RNA interference(RNAi)has emerged as a promising technology for insect control.The green peach aphid,Myzus persicae,feeds on over 400 species of host plants.Brassica napus(rape)is the second most important oilseed crop worldwide.Myzus persicae is highly reproductive and causes severe damage to the rape plants due to its quite flexible life cycle.In this study,we tested the RNAi effects of transgenic rape plants on M.persicae.By in vitro feeding M.persicae with artificial diets containing double-stranded RNAs(dsRNAs)targeting seven aphid genes,we identified a new gene encoding the partitioning-defective protein 6(Par6)as the most potent RNAi target.Tissue-and stage-expression analysis of Par6 suggested this gene is highly expressed in the embryo and adult stage of M.persicae.We next generated transgenic rape plants expressing ds Par6 by Agrobacteriummediated transformation and obtained nine independent transgenic lines.Compared to wild-type control plants,transgenic rape lines expressing ds Par6 showed strong resistance to M.persicae.Feeding assays revealed that feeding transgenic rape plants to M.persicae significantly decreased MpPar6 expression and survival rate and impaired fecundity.Furthermore,we showed that the resistance levels to M.persicae are positively correlated with ds Par6 expression levels in transgenic rape plants.Our study demonstrates that transgenic rape plants expressing ds Par6 are efficiently protected from M.persicae.Interfering with the genes involved in embryo development could be the effective RNAi targets for controlling aphids and potentially other insect pests.
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 Guangdong Basic and Applied Basic Research Foundation(2023A1515010969)Natural Science Foundation of Top Talent of SZTU(GDRC202305).
文摘Anti-tumor angiogenesis therapy, targeting the suppression of blood vessel growth in tumors, presents a potent approach in the battle against cancer. Traditional therapies have primarily concentrated on single-target techniques, with a specific emphasis on targeting the vascular endothelial growth factor, but have not reached ideal therapeutic efficacy. In response to this issue, our study introduced a novel nanoparticle system known as CS-siRNA/PEITC&L-cRGD NPs. These chitosan-based nanoparticles have been recognized for their excellent biocompatibility and ability to deliver genes. To enhance their targeted delivery capability, they were combined with a cyclic RGD peptide (cRGD). Targeted co-delivery of gene and chemotherapeutic agents was achieved through the use of a negatively charged lipid shell and cRGD, which possesses high affinity for integrin αvβ3 overexpressed in tumor cells and neovasculature. In this multifaceted approach, co-delivery of VEGF siRNA and phenethyl isothiocyanate (PEITC) was employed to target both tumor vascular endothelial cells and tumor cells simultaneously. The co-delivery of VEGF siRNA and PEITC could achieve precise silencing of VEGF, inhibit the accumulation of HIF-1α under hypoxic conditions, and induce apoptosis in tumor cells. In summary, we have successfully developed a nanoparticle delivery platform that utilizes a dual mechanism of action of anti-tumor angiogenesis and pro-tumor apoptosis, which provides a robust and potent strategy for the delivery of anti-cancer therapeutics.
