Parkinson’s disease is a common neurodegenerative disorder that is associated with abnormal aggregation and accumulation of neurotoxic proteins,includingα-synuclein,amyloid-β,and tau,in addition to the impaired eli...Parkinson’s disease is a common neurodegenerative disorder that is associated with abnormal aggregation and accumulation of neurotoxic proteins,includingα-synuclein,amyloid-β,and tau,in addition to the impaired elimination of these neurotoxic protein.Atypical parkinsonism,which has the same clinical presentation and neuropathology as Parkinson’s disease,expands the disease landscape within the continuum of Parkinson’s disease and related disorders.The glymphatic system is a waste clearance system in the brain,which is responsible for eliminating the neurotoxic proteins from the interstitial fluid.Impairment of the glymphatic system has been proposed as a significant contributor to the development and progression of neurodegenerative disease,as it exacerbates the aggregation of neurotoxic proteins and deteriorates neuronal damage.Therefore,impairment of the glymphatic system could be considered as the final common pathway to neurodegeneration.Previous evidence has provided initial insights into the potential effect of the impaired glymphatic system on Parkinson’s disease and related disorders;however,many unanswered questions remain.This review aims to provide a comprehensive summary of the growing literature on the glymphatic system in Parkinson’s disease and related disorders.The focus of this review is on identifying the manifestations and mechanisms of interplay between the glymphatic system and neurotoxic proteins,including loss of polarization of aquaporin-4 in astrocytic endfeet,sleep and circadian rhythms,neuroinflammation,astrogliosis,and gliosis.This review further delves into the underlying pathophysiology of the glymphatic system in Parkinson’s disease and related disorders,and the potential implications of targeting the glymphatic system as a novel and promising therapeutic strategy.展开更多
AIM:To analyze the distribution of refractive status in school-age children with different corneal curvatures(CC)and the correlation between CC and refractive status.METHODS:A total of 2214 school-aged children of gra...AIM:To analyze the distribution of refractive status in school-age children with different corneal curvatures(CC)and the correlation between CC and refractive status.METHODS:A total of 2214 school-aged children of grade 4 in Hangzhou who were screened for school myopia were included.Uncorrected distance visual acuity(UCDVA),non-cycloplegic refraction,axial length(AL),horizontal and vertical corneal curvature(K1,K2)were measured and spherical equivalent(SE),corneal curvature radius(CCR)and axial length/corneal radius of curvature ratio(AL/CR)were calculated.UCDVA<5.0 and SE≤-0.50 D were classified as school-screening myopia.According to the different CCRs,the patients were divided into the lower corneal curvature(LCC)group(CCR≥7.92)and the higher corneal curvature(HCC)group(CCR<7.92).Each group was further divided into the normal AL subgroup and the long AL subgroup.The refractive parameters were compared to identify any differences between the two groups.RESULTS:Both SE and AL were greater in the LCC group(P=0.013,P<0.001).The prevalence of myopia was 38% in the LCC group and 44% in the HCC group(P<0.001).The proportion of children without screening myopia was higher in the LCC group(62%)than in the HCC group(56%).Among these children without screening myopia,the proportion of long AL in the LCC group(24%)was significantly higher than that in the HCC group(0.012%;P<0.001).The change of SE in the LCC group was less affected by the increase of AL than that in the HCC group.CONCLUSION:School-aged children in the LCC group have a lower incidence of screening myopia and longer AL.Low CC can mask SE reduction and AL growth to some extent,and the change of AL growth change more in children with low CC than high CC.Before the onset of myopia,its growth rate is even faster than that after the onset of myopia.展开更多
Differentiation of human fibroblasts into functional neurons depends on the introduction of viral-mediated transcription factors, which present risks of viral gene integration and tumorigenicity. In recent years, alth...Differentiation of human fibroblasts into functional neurons depends on the introduction of viral-mediated transcription factors, which present risks of viral gene integration and tumorigenicity. In recent years, although some studies have been successful in directly inducing neurons through sustained expression of small molecule compounds, they have only been shown to be effective on mouse-derived cells. Thus, herein we delivered vectors containing Epstein-Barr virus-derived oriP/Epstein-Barr nuclear antigen 1 encoding the neuronal transcription factor, Ascl1, the neuron-specific microRNA, miR124, and a small hairpin directed against p53, into human fibroblasts. Cells were incubated in a neuron-inducing culture medium. Immunofluorescence staining was used to detect Tuj-1, microtubule-associated protein 2, neuron-specific nucleoprotein NeuN and nerve cell adhesion molecules in the induced cells. The proportion of Tuj1-positive cells was up to 36.7% after induction for 11 days. From day 21, these induced neurons showed neuron-specific expression patterns of microtubule-associated protein 2, NeuN and neural cell adhesion molecule. Our approach is a simple, plasmid-based process that enables direct reprogramming of human fibroblasts into neurons, and provides alternative avenues for disease modeling and neurodegenerative medicine.展开更多
To date, the instability of organometal halide perovskite solar cells（PSCs） has become the focus issue that limits the development and long-term application of PSCs. Both the ultraviolet（UV） rays in sunlight and m...To date, the instability of organometal halide perovskite solar cells（PSCs） has become the focus issue that limits the development and long-term application of PSCs. Both the ultraviolet（UV） rays in sunlight and moisture in air can significantly accelerate the disintegration of the perovskite. Here, we introduced a Zn Se quantum dots layer as downshifting materials, which was spin-coated onto the backside of PSCs.This layer converted the UV rays into visible light to prevent the destruction of PSCs as well as increase the light harvesting of the perovskite layer. Under the UV irradiation in the moisture ambient（40%）, the destruction speed of the unencapsulated perovskite films were also delayed evidently. In addition, the power conversion efficiency（PCE） of the PSCs was increased from 16.6% to 17.3% due to the increase of the visible light absorbance of the perovskite.展开更多
Multiple single nucleotide polymorphisms may contribute to cognitive decline in Parkinson’s disease. However, the mechanism by which these single nucleotide polymorphisms modify brain imaging phenotype remains unclea...Multiple single nucleotide polymorphisms may contribute to cognitive decline in Parkinson’s disease. However, the mechanism by which these single nucleotide polymorphisms modify brain imaging phenotype remains unclear. The aim of this study was to investigate the potential effects of multiple single nucleotide polymorphisms on brain imaging phenotype in Parkinson’s disease. Forty-eight Parkinson’s disease patients and 39 matched healthy controls underwent genotyping and 7 T magnetic resonance imaging. A cognitive-weighted polygenic risk score model was designed, in which the effect sizes were determined individually for 36 single nucleotide polymorphisms. The correlations between polygenic risk score, neuroimaging features, and clinical data were analyzed. Furthermore, individual single nucleotide polymorphism analysis was performed to explore the main effects of genotypes and their interactive effects with Parkinson’s disease diagnosis. We found that, in Parkinson’s disease, the polygenic risk score was correlated with the neural activity of the hippocampus, parahippocampus, and fusiform gyrus, and with hippocampal-prefrontal and fusiform-temporal connectivity, as well as with gray matter alterations in the orbitofrontal cortex. In addition, we found that single nucleotide polymorphisms in α-synuclein(SNCA) were associated with white matter microstructural changes in the superior corona radiata, corpus callosum, and external capsule. A single nucleotide polymorphism in catechol-O-methyltransferase was associated with the neural activities of the lingual, fusiform, and occipital gyri, which are involved in visual cognitive dysfunction. Furthermore, DRD3 was associated with frontal and temporal lobe function and structure. In conclusion, imaging genetics is useful for providing a better understanding of the genetic pathways involved in the pathophysiologic processes underlying Parkinson’s disease. This study provides evidence of an association between genetic factors, cognitive functions, and multi-modality neuroimaging biomarkers in Parkinson’s disease.展开更多
Examining the retinal tissue has the potential to provide a unique method and technique to quantify Alzheimer’s disease-related changes in participants at various stages of the disease.In this metaanalysis,we aimed t...Examining the retinal tissue has the potential to provide a unique method and technique to quantify Alzheimer’s disease-related changes in participants at various stages of the disease.In this metaanalysis,we aimed to investigate the association of various optical coherence tomography parameters with Alzheimer’s disease and whether retinal measurements can be used to diffe rentiate between Alzheimer’s disease and control subjects.Scientific databases including Google Schola r,Web of Science,and PubMed were systematically searched for published articles that evaluated retinal nerve fiber layer thickness and retinal microvascular network in Alzheimer’s disease and control subjects.Seventy-three studies(5850 participants,including 2249 Alzheimer’s disease patients and 3601controls) were included in this meta-analysis.Relative to controls,Alzheimer’s disease patients had a significantly lower global retinal nerve fiber layer thickness(standardized mean difference [SMD]=-0.79,95% confidence intervals [CI]:-1.03 to-0.54,P <0.00001) as well as each quadrant being thinner in Alzheimer’s disease versus controls.Regarding macular paramete rs,values measured by optical coherence tomography were significantly lower in Alzheimer’s disease than controls for macular thickness(pooled SMD:-0.44,95% CI:-0.67 to-0.20,P=0.0003),foveal thickness(pooled SMD=-0.39,95% CI:-0.58 to-0.19,P <0.0001),ganglion cell inner plexiform layer(SMD=-1.26,95% CI:-2.24 to-0.27,P=0.01) and macular volume(pooled SMD=-0.41,95% CI-0.76 to-0.07,P=0.02).Analysis using optical coherence tomography angiography parameters revealed mixed results between Alzheimer’s disease and controls.Superficial vessel density(pooled SMD=-0.42,95% CI:-0.68 to-0.17,P=0.0001) and deep vessel density(pooled SMD=-0.46,95% CI:-0.75 to-0.18,P=0.001) were found to be thinner in Alzheimer’s disease patients whereas the foveal avascular zone(SMD=0.84,95% CI:0.17-1.51,P=0.01) was larger in controls.Vascular density and thickness of various retinal laye rs were decreased in Alzheimer’s disease patients compared to controls.Our results provide evidence for optical coherence tomography technology having the potential to detect retinal and microvascular changes in patients diagnosed with Alzheimer’s disease and aid in monito ring and early diagnosis methods.展开更多
Anthocyanins are the most widely produced secondary metabolites in plants,and they play an important role in plant growth and reproduction.The nitrogen source is an important factor affecting anthocyanin production,bu...Anthocyanins are the most widely produced secondary metabolites in plants,and they play an important role in plant growth and reproduction.The nitrogen source is an important factor affecting anthocyanin production,but the nitrogen concentrations on metabolism and the underlying genetic basis remain unclear.In this study,in vitro anthocyanin induction was conducted on Malus spectabilis.The leaf explants were cultivated in media containing different nitrogen concentrations.The results suggested that when the nitrogen contents decreased in limit,the color of leaf explants turned from green to red,and increased anthocyanin accumulation led to a change in phenotype.Furthermore,the content of other flavonoids,such as dihydroquercetin,epicatechin,and catechin,increased under low nitrogen conditions.The transcription levels of the general flavonoid pathway genes,from phenylalanine ammonia lyase(PAL)to anthocyanidin synthase(ANS),were associated with the concentration of corresponding flavonoid compounds and phenotype changes.In particular,the expression level of ANS increased substantially under a low nitrogen treatment,which was significantly and positively correlated with the anthocyanin levels(R2=0.72,P<0.05).The increased expression patterns of anthocyanin pathway genes were similar to that of the transcription factor MYB10.We further verified MYB10 played an important role in the anthocyanin pathway in leaves of Malus spectabilis.These results suggested that we can improve the desirable ornamental plant phenotypes by controlling nitrogen content.This process may offer clues to further development of new agricultural practices.展开更多
AIM：To investigate the impact of adipose-derived mesenchymal stem cells（ADSCs） on cell viability and extracellular matrix（ECM） synthesis of corneal stromal cells（CSCs）. METHODS：ADSCs and CSCs were obtained fro...AIM：To investigate the impact of adipose-derived mesenchymal stem cells（ADSCs） on cell viability and extracellular matrix（ECM） synthesis of corneal stromal cells（CSCs）. METHODS：ADSCs and CSCs were obtained from the corneas of New Zealand white rabbits and indirectly cocultured in vitro. The proliferative capacity of CSCs in the different groups was assessed by CCK-8 assays. Annexin V-fluorescein isothiocyanate（FITC）/proliferation indices（PI） assays were used to detect the apoptosis of CSCs. The expression levels of matrix metalloproteinase（MMP）, such as MMP1, MMP2, MMP9, and collagens were also evaluated by Western blot. RESULTS：ADSCs significantly promoted proliferation and invasion of CSCs in the indirect co-culture assays. The co-cultural group displayed much higher ability of proliferation, especially under the co-culture conditions of ADSCs for 3d, compared with that CSCs cultured alone. The PI of CSCs in the co-culture system were increased approximately 3-8-fold compared with the control group. A significant change was observed in the proportions of cells at apoptosis（early and late） between the negative control group（6.34% and 2.06%） and the ADCSs-treated group（4.69% and 1.59%）. The expression levels of MMPs were down regulated in the co-culture models. Compared with the control group, the decrease intensities of MMP-1, MMP-2 and MMP-9 in CSCs/ADSCs group were observed, 3.90-fold, 1.09-fold and 3.03-fold, respectively. However, the increase intensities of collagen type（I, II, III, IV, and V） in CSCs were observed in CSCs/ADSCs group, 3.47-fold,4.30-fold, 2.35-fold, 2.55-fold and 2.43-fold, respectively, compared to that in the control group. The expressions of aldehyde dehydrogenase and fibronectin in CSCs were upregulated in the co-culture models.CONCLUSION：ADSCs play a promotive role in CSCs＇ growth and invasion, which may be partially associated with MMPs decrease and collagens increase, resulting in a positive participation in the plasticity and ECM synthesis of CSCs. This provided a new insight into the extensive role of ADSCs in CSCs and a potential molecular target for corneal therapy.展开更多
Background Evidence from clinical and preclinical studies has demonstrated that stress can cause depressive-like symptoms including anhedonia and psychomotor retardation, namely, the manifestation of motivational defi...Background Evidence from clinical and preclinical studies has demonstrated that stress can cause depressive-like symptoms including anhedonia and psychomotor retardation, namely, the manifestation of motivational deficits in depression. The proximate mediator of linking social-environmental stress with internal motivational deficits remains elusive, although substantial studies proposed neural endocrine mechanisms. As an endogenous danger-associated molecule, high mobility group box-1 (HMGB1) is necessary and sufficient for stress-induced sensitization of innate immune cells and subsequent (neuro)inflammation. Aim This review aims to provide evidence to unveil the potential mechanism of the relationship between motivational deficits and stress in depression. M ethods We reviewed original case-control studies investigating the association between HMGB1-mediated inflammation and stress-induced depression. The literature search of Pubmed and Web of Science electronic database from Inception up to March 28th, 2019 were conducted by two independent authors. We performed a qualitative systematic review approach to explore the correlation between HMGB1 -mediated inflammation and anhedonia/psychomotor retardation in depression. Results A total of 69 studies based on search strategy were retrieved and seven eligible studies met the inclusion criteria. Studies showed that HMGB1 was implicated with depressive-like behaviors, which are similar with motivational deficits. Furthermore, HMGB1 -mediated inflammation in depressive-like behaviors may be involved in Nod-like receptor family pyrin domain containing three (NLRP3) inflammasome and proinflammatory cytokines, abnormal kynurenine pathway and imbalance between neuroprotective and neurotoxic factors. Conclusions We found that stress-induced inflammation mediated by HMGB1 may affect motivational deficits through regulating dopamine pathway in corticostriatal neurocircuitry. The systematic review may shed light on the novel neurobiological underpinning for treatment of motivation deficits in depression.展开更多
BACKGROUND Since December 2019,there have been many new cases of coronavirus pneumonia in Wuhan,Hubei Province,which has gradually spread throughout the country.AIM To explore our hospital’s innovative management sys...BACKGROUND Since December 2019,there have been many new cases of coronavirus pneumonia in Wuhan,Hubei Province,which has gradually spread throughout the country.AIM To explore our hospital’s innovative management system to ensure the efficient operation of fever clinics during the epidemic,since controlling the spread of disease is an important way to prevent and control the epidemic.METHODS In total,200 outpatients with fever at our hospital between November 2019 and July 2020 were selected and allocated into two groups.RESULTS The fever clinic in our hospital operated smoothly,and infection with the novel coronavirus disease(COVID-19)has not been reported in our hospital.Additionally,we did not have any cases of missed diagnosis.The awareness regarding COVID-19 infection sources,transmission routes,early symptoms,and preventive measures was significantly higher in our fever clinic than in those of the pre-management group.CONCLUSION"An integrated system,three separate responsibilities"ensured the efficient functioning of our fever outpatient clinic and early screening of COVID-19 cases,which effectively curbed the transmission of COVID-19 and hence prevented COVID-19 pneumonia epidemic in our hospital,ultimately achieving the maximum effect of epidemic prevention and control.展开更多
Dear sir,Iam Dr.Wen-Wei Li,from the Department of Ophthalmology,Zhejiang Provincial People’s Hospital,Hangzhou,China.I write to present a case of ocular leech infestation initially misdiagnosed as conjunctival pigmen...Dear sir,Iam Dr.Wen-Wei Li,from the Department of Ophthalmology,Zhejiang Provincial People’s Hospital,Hangzhou,China.I write to present a case of ocular leech infestation initially misdiagnosed as conjunctival pigmented nevus.Although human interaction with leeches is not uncommon展开更多
Huntington’s disease(HD)is an autosomal dominant neurodegenerative disease that is caused by a cytosine-adenine-guanine(CAG)expansion in the first exon of the huntingtin(HTT)gene,which codes for the hun-tingtin prote...Huntington’s disease(HD)is an autosomal dominant neurodegenerative disease that is caused by a cytosine-adenine-guanine(CAG)expansion in the first exon of the huntingtin(HTT)gene,which codes for the hun-tingtin protein.It typically manifests with a triad of symptoms,including motor disorders,cognitive impair-ment and psychiatric disturbances[1].HD primar-ily affects the basal ganglia(BG),especially the caudate and putamen,after which it extends to more widespread gray and white matter[2].Perivascular spaces(PVSs)are fluid-filled extensions of the subarachnoid spaces that enclose cerebral blood vessels and extend from the cer-ebral cortex through the brain parenchyma.The physi-ological role of PVSs is the drainage of brain interstitial fluid into perivascular pathways for the elimination of waste products through the glymphatic drainage sys-tem.An increasing number of studies have demonstrated that enlarged PVSs indicate glymphatic dysfunction and are associated with many neurological diseases,such as Alzheimer’s disease,Parkinson’s disease and small vessel disease[3].With the advantage of strong field strengths,7.0 T images show superior resolution and signal-to-noise ratios than 3.0 T,which facilitate the visualization of PVS.And automated segmentation methods could accurately identify PVS in a short time with no inter-rater variability.In the current study,we used U-shaped networks(U-net),a class of deep learning methods,to explore the PVS distribution in HD and controls.To date,PVS distribution in HD is still unclear.Only two studies have investigated PVSs in HD,and both dem-onstrated increased visible PVS burden in manifest HD compared to controls[4,5].However,whether PVS bur-den increases in premanifest HD(pre-HD)individuals remains unknown,and the relationship of PVS with cog-nitive decline has never been studied.展开更多
Background TDP-43 proteinopathies represent a spectrum of neurological disorders,anchored clinically on either end by amyotrophic lateral sclerosis(ALS)and frontotemporal degeneration(FTD).The ALS-FTD spectrum exhibit...Background TDP-43 proteinopathies represent a spectrum of neurological disorders,anchored clinically on either end by amyotrophic lateral sclerosis(ALS)and frontotemporal degeneration(FTD).The ALS-FTD spectrum exhibits a diverse range of clinical presentations with overlapping phenotypes,highlighting its heterogeneity.This study was aimed to use disease progression modeling to identify novel data-driven spatial and temporal subtypes of brain atrophy and its progression in the ALS-FTD spectrum.Methods We used a data-driven procedure to identify 13 anatomic clusters of brain volume for 57 behavioral variant FTD(bvFTD;with either autopsy-confirmed TDP-43 or TDP-43 proteinopathy-associated genetic variants),103 ALS,and 47 ALS-FTD patients with likely TDP-43.A Subtype and Stage Inference(SuStaIn)model was trained to identify subtypes of individuals along the ALS-FTD spectrum with distinct brain atrophy patterns,and we related subtypes and stages to clinical,genetic,and neuropathological features of disease.Results SuStaIn identified three novel subtypes:two disease subtypes with predominant brain atrophy in either prefrontal/somatomotor regions or limbic-related regions,and a normal-appearing group without obvious brain atrophy.The limbic-predominant subtype tended to present with more impaired cognition,higher frequencies of pathogenic variants in TBK1 and TARDBP genes,and a higher proportion of TDP-43 types B,E and C.In contrast,the prefrontal/somatomotor-predominant subtype had higher frequencies of pathogenic variants in C9orf72 and GRN genes and higher proportion of TDP-43 type A.The normal-appearing brain group showed higher frequency of ALS relative to ALS-FTD and bvFTD patients,higher cognitive capacity,higher proportion of lower motor neuron onset,milder motor symptoms,and lower frequencies of genetic pathogenic variants.The overall SuStaIn stages also correlated with evidence for clinical progression including longer disease duration,higher King’s stage,and cognitive decline.Additionally,SuStaIn stages differed across clinical phenotypes,genotypes and types of TDP-43 pathology.Conclusions Our findings suggest distinct neurodegenerative subtypes of disease along the ALS-FTD spectrum that can be identified in vivo,each with distinct brain atrophy,clinical,genetic and pathological patterns.展开更多
基金supported by the National Key R&D Program of China,No.2021YFF0702203(to HYL)the National Natural Science Foundation of China,No.82101323(to TS)Preferred Foundation of Zhejiang Postdoctors,No.ZJ2021152(to TS).
文摘Parkinson’s disease is a common neurodegenerative disorder that is associated with abnormal aggregation and accumulation of neurotoxic proteins,includingα-synuclein,amyloid-β,and tau,in addition to the impaired elimination of these neurotoxic protein.Atypical parkinsonism,which has the same clinical presentation and neuropathology as Parkinson’s disease,expands the disease landscape within the continuum of Parkinson’s disease and related disorders.The glymphatic system is a waste clearance system in the brain,which is responsible for eliminating the neurotoxic proteins from the interstitial fluid.Impairment of the glymphatic system has been proposed as a significant contributor to the development and progression of neurodegenerative disease,as it exacerbates the aggregation of neurotoxic proteins and deteriorates neuronal damage.Therefore,impairment of the glymphatic system could be considered as the final common pathway to neurodegeneration.Previous evidence has provided initial insights into the potential effect of the impaired glymphatic system on Parkinson’s disease and related disorders;however,many unanswered questions remain.This review aims to provide a comprehensive summary of the growing literature on the glymphatic system in Parkinson’s disease and related disorders.The focus of this review is on identifying the manifestations and mechanisms of interplay between the glymphatic system and neurotoxic proteins,including loss of polarization of aquaporin-4 in astrocytic endfeet,sleep and circadian rhythms,neuroinflammation,astrogliosis,and gliosis.This review further delves into the underlying pathophysiology of the glymphatic system in Parkinson’s disease and related disorders,and the potential implications of targeting the glymphatic system as a novel and promising therapeutic strategy.
基金Supported by Key Research and Development Projects of Zhejiang Science and Technology Plan(No.2021C03103).
文摘AIM:To analyze the distribution of refractive status in school-age children with different corneal curvatures(CC)and the correlation between CC and refractive status.METHODS:A total of 2214 school-aged children of grade 4 in Hangzhou who were screened for school myopia were included.Uncorrected distance visual acuity(UCDVA),non-cycloplegic refraction,axial length(AL),horizontal and vertical corneal curvature(K1,K2)were measured and spherical equivalent(SE),corneal curvature radius(CCR)and axial length/corneal radius of curvature ratio(AL/CR)were calculated.UCDVA<5.0 and SE≤-0.50 D were classified as school-screening myopia.According to the different CCRs,the patients were divided into the lower corneal curvature(LCC)group(CCR≥7.92)and the higher corneal curvature(HCC)group(CCR<7.92).Each group was further divided into the normal AL subgroup and the long AL subgroup.The refractive parameters were compared to identify any differences between the two groups.RESULTS:Both SE and AL were greater in the LCC group(P=0.013,P<0.001).The prevalence of myopia was 38% in the LCC group and 44% in the HCC group(P<0.001).The proportion of children without screening myopia was higher in the LCC group(62%)than in the HCC group(56%).Among these children without screening myopia,the proportion of long AL in the LCC group(24%)was significantly higher than that in the HCC group(0.012%;P<0.001).The change of SE in the LCC group was less affected by the increase of AL than that in the HCC group.CONCLUSION:School-aged children in the LCC group have a lower incidence of screening myopia and longer AL.Low CC can mask SE reduction and AL growth to some extent,and the change of AL growth change more in children with low CC than high CC.Before the onset of myopia,its growth rate is even faster than that after the onset of myopia.
基金supported by the National Natural Science Foundation of China,No.81471126(to XZC)and 81771216(to XZC)the Natural Science Foundation of Zhejiang Province of China,No.LY17H090005(to JLP)a grant from the Medical Science and Technology Plan Project of Zhejiang Province of China,No.2016KYB119(to JLP)
文摘Differentiation of human fibroblasts into functional neurons depends on the introduction of viral-mediated transcription factors, which present risks of viral gene integration and tumorigenicity. In recent years, although some studies have been successful in directly inducing neurons through sustained expression of small molecule compounds, they have only been shown to be effective on mouse-derived cells. Thus, herein we delivered vectors containing Epstein-Barr virus-derived oriP/Epstein-Barr nuclear antigen 1 encoding the neuronal transcription factor, Ascl1, the neuron-specific microRNA, miR124, and a small hairpin directed against p53, into human fibroblasts. Cells were incubated in a neuron-inducing culture medium. Immunofluorescence staining was used to detect Tuj-1, microtubule-associated protein 2, neuron-specific nucleoprotein NeuN and nerve cell adhesion molecules in the induced cells. The proportion of Tuj1-positive cells was up to 36.7% after induction for 11 days. From day 21, these induced neurons showed neuron-specific expression patterns of microtubule-associated protein 2, NeuN and neural cell adhesion molecule. Our approach is a simple, plasmid-based process that enables direct reprogramming of human fibroblasts into neurons, and provides alternative avenues for disease modeling and neurodegenerative medicine.
基金supported by the National Science Foundation of China (51774034, 51772026, 51611130063)the Fundamental Research Funds for the Central Universities (FRF-BD-16-012A)111 Project (No. B17003)
文摘To date, the instability of organometal halide perovskite solar cells（PSCs） has become the focus issue that limits the development and long-term application of PSCs. Both the ultraviolet（UV） rays in sunlight and moisture in air can significantly accelerate the disintegration of the perovskite. Here, we introduced a Zn Se quantum dots layer as downshifting materials, which was spin-coated onto the backside of PSCs.This layer converted the UV rays into visible light to prevent the destruction of PSCs as well as increase the light harvesting of the perovskite layer. Under the UV irradiation in the moisture ambient（40%）, the destruction speed of the unencapsulated perovskite films were also delayed evidently. In addition, the power conversion efficiency（PCE） of the PSCs was increased from 16.6% to 17.3% due to the increase of the visible light absorbance of the perovskite.
基金supported by grants from the National Natural Science Foundation of China,Nos. 81771216 (to JLP), 81520108010 (to BRZ),and 82101323 (to TS)the National Key R&D Program of China,No. 2018YFA0701400 (to HYL)+3 种基金the Primary Research and Development Plan of Zhejiang Province,No. 2020C03020 (to BRZ)the Key Project of Zhejiang Laboratory,No. 2018EB0ZX01 (to HYL)the Fundamental Research Funds for the Central Universities,No. 2019XZZX001-01-21 (to HYL)Preferred Foundation of Zhejiang Postdoctors,No. ZJ2021152 (to TS)。
文摘Multiple single nucleotide polymorphisms may contribute to cognitive decline in Parkinson’s disease. However, the mechanism by which these single nucleotide polymorphisms modify brain imaging phenotype remains unclear. The aim of this study was to investigate the potential effects of multiple single nucleotide polymorphisms on brain imaging phenotype in Parkinson’s disease. Forty-eight Parkinson’s disease patients and 39 matched healthy controls underwent genotyping and 7 T magnetic resonance imaging. A cognitive-weighted polygenic risk score model was designed, in which the effect sizes were determined individually for 36 single nucleotide polymorphisms. The correlations between polygenic risk score, neuroimaging features, and clinical data were analyzed. Furthermore, individual single nucleotide polymorphism analysis was performed to explore the main effects of genotypes and their interactive effects with Parkinson’s disease diagnosis. We found that, in Parkinson’s disease, the polygenic risk score was correlated with the neural activity of the hippocampus, parahippocampus, and fusiform gyrus, and with hippocampal-prefrontal and fusiform-temporal connectivity, as well as with gray matter alterations in the orbitofrontal cortex. In addition, we found that single nucleotide polymorphisms in α-synuclein(SNCA) were associated with white matter microstructural changes in the superior corona radiata, corpus callosum, and external capsule. A single nucleotide polymorphism in catechol-O-methyltransferase was associated with the neural activities of the lingual, fusiform, and occipital gyri, which are involved in visual cognitive dysfunction. Furthermore, DRD3 was associated with frontal and temporal lobe function and structure. In conclusion, imaging genetics is useful for providing a better understanding of the genetic pathways involved in the pathophysiologic processes underlying Parkinson’s disease. This study provides evidence of an association between genetic factors, cognitive functions, and multi-modality neuroimaging biomarkers in Parkinson’s disease.
基金National Health and Medical Research Council (NHMRC) Australia (to VG)。
文摘Examining the retinal tissue has the potential to provide a unique method and technique to quantify Alzheimer’s disease-related changes in participants at various stages of the disease.In this metaanalysis,we aimed to investigate the association of various optical coherence tomography parameters with Alzheimer’s disease and whether retinal measurements can be used to diffe rentiate between Alzheimer’s disease and control subjects.Scientific databases including Google Schola r,Web of Science,and PubMed were systematically searched for published articles that evaluated retinal nerve fiber layer thickness and retinal microvascular network in Alzheimer’s disease and control subjects.Seventy-three studies(5850 participants,including 2249 Alzheimer’s disease patients and 3601controls) were included in this meta-analysis.Relative to controls,Alzheimer’s disease patients had a significantly lower global retinal nerve fiber layer thickness(standardized mean difference [SMD]=-0.79,95% confidence intervals [CI]:-1.03 to-0.54,P <0.00001) as well as each quadrant being thinner in Alzheimer’s disease versus controls.Regarding macular paramete rs,values measured by optical coherence tomography were significantly lower in Alzheimer’s disease than controls for macular thickness(pooled SMD:-0.44,95% CI:-0.67 to-0.20,P=0.0003),foveal thickness(pooled SMD=-0.39,95% CI:-0.58 to-0.19,P <0.0001),ganglion cell inner plexiform layer(SMD=-1.26,95% CI:-2.24 to-0.27,P=0.01) and macular volume(pooled SMD=-0.41,95% CI-0.76 to-0.07,P=0.02).Analysis using optical coherence tomography angiography parameters revealed mixed results between Alzheimer’s disease and controls.Superficial vessel density(pooled SMD=-0.42,95% CI:-0.68 to-0.17,P=0.0001) and deep vessel density(pooled SMD=-0.46,95% CI:-0.75 to-0.18,P=0.001) were found to be thinner in Alzheimer’s disease patients whereas the foveal avascular zone(SMD=0.84,95% CI:0.17-1.51,P=0.01) was larger in controls.Vascular density and thickness of various retinal laye rs were decreased in Alzheimer’s disease patients compared to controls.Our results provide evidence for optical coherence tomography technology having the potential to detect retinal and microvascular changes in patients diagnosed with Alzheimer’s disease and aid in monito ring and early diagnosis methods.
基金National Natural Science Foundation of China(Grant No.31570697)Central Financial Appropriation for Forestry Promotion and Assistance Projects(Grant No.[2016]03).
文摘Anthocyanins are the most widely produced secondary metabolites in plants,and they play an important role in plant growth and reproduction.The nitrogen source is an important factor affecting anthocyanin production,but the nitrogen concentrations on metabolism and the underlying genetic basis remain unclear.In this study,in vitro anthocyanin induction was conducted on Malus spectabilis.The leaf explants were cultivated in media containing different nitrogen concentrations.The results suggested that when the nitrogen contents decreased in limit,the color of leaf explants turned from green to red,and increased anthocyanin accumulation led to a change in phenotype.Furthermore,the content of other flavonoids,such as dihydroquercetin,epicatechin,and catechin,increased under low nitrogen conditions.The transcription levels of the general flavonoid pathway genes,from phenylalanine ammonia lyase(PAL)to anthocyanidin synthase(ANS),were associated with the concentration of corresponding flavonoid compounds and phenotype changes.In particular,the expression level of ANS increased substantially under a low nitrogen treatment,which was significantly and positively correlated with the anthocyanin levels(R2=0.72,P<0.05).The increased expression patterns of anthocyanin pathway genes were similar to that of the transcription factor MYB10.We further verified MYB10 played an important role in the anthocyanin pathway in leaves of Malus spectabilis.These results suggested that we can improve the desirable ornamental plant phenotypes by controlling nitrogen content.This process may offer clues to further development of new agricultural practices.
基金Supported by Important Subject Fund of Science Technology Department of Zhejiang Province(No.2013C03048-1)
文摘AIM：To investigate the impact of adipose-derived mesenchymal stem cells（ADSCs） on cell viability and extracellular matrix（ECM） synthesis of corneal stromal cells（CSCs）. METHODS：ADSCs and CSCs were obtained from the corneas of New Zealand white rabbits and indirectly cocultured in vitro. The proliferative capacity of CSCs in the different groups was assessed by CCK-8 assays. Annexin V-fluorescein isothiocyanate（FITC）/proliferation indices（PI） assays were used to detect the apoptosis of CSCs. The expression levels of matrix metalloproteinase（MMP）, such as MMP1, MMP2, MMP9, and collagens were also evaluated by Western blot. RESULTS：ADSCs significantly promoted proliferation and invasion of CSCs in the indirect co-culture assays. The co-cultural group displayed much higher ability of proliferation, especially under the co-culture conditions of ADSCs for 3d, compared with that CSCs cultured alone. The PI of CSCs in the co-culture system were increased approximately 3-8-fold compared with the control group. A significant change was observed in the proportions of cells at apoptosis（early and late） between the negative control group（6.34% and 2.06%） and the ADCSs-treated group（4.69% and 1.59%）. The expression levels of MMPs were down regulated in the co-culture models. Compared with the control group, the decrease intensities of MMP-1, MMP-2 and MMP-9 in CSCs/ADSCs group were observed, 3.90-fold, 1.09-fold and 3.03-fold, respectively. However, the increase intensities of collagen type（I, II, III, IV, and V） in CSCs were observed in CSCs/ADSCs group, 3.47-fold,4.30-fold, 2.35-fold, 2.55-fold and 2.43-fold, respectively, compared to that in the control group. The expressions of aldehyde dehydrogenase and fibronectin in CSCs were upregulated in the co-culture models.CONCLUSION：ADSCs play a promotive role in CSCs＇ growth and invasion, which may be partially associated with MMPs decrease and collagens increase, resulting in a positive participation in the plasticity and ECM synthesis of CSCs. This provided a new insight into the extensive role of ADSCs in CSCs and a potential molecular target for corneal therapy.
文摘Background Evidence from clinical and preclinical studies has demonstrated that stress can cause depressive-like symptoms including anhedonia and psychomotor retardation, namely, the manifestation of motivational deficits in depression. The proximate mediator of linking social-environmental stress with internal motivational deficits remains elusive, although substantial studies proposed neural endocrine mechanisms. As an endogenous danger-associated molecule, high mobility group box-1 (HMGB1) is necessary and sufficient for stress-induced sensitization of innate immune cells and subsequent (neuro)inflammation. Aim This review aims to provide evidence to unveil the potential mechanism of the relationship between motivational deficits and stress in depression. M ethods We reviewed original case-control studies investigating the association between HMGB1-mediated inflammation and stress-induced depression. The literature search of Pubmed and Web of Science electronic database from Inception up to March 28th, 2019 were conducted by two independent authors. We performed a qualitative systematic review approach to explore the correlation between HMGB1 -mediated inflammation and anhedonia/psychomotor retardation in depression. Results A total of 69 studies based on search strategy were retrieved and seven eligible studies met the inclusion criteria. Studies showed that HMGB1 was implicated with depressive-like behaviors, which are similar with motivational deficits. Furthermore, HMGB1 -mediated inflammation in depressive-like behaviors may be involved in Nod-like receptor family pyrin domain containing three (NLRP3) inflammasome and proinflammatory cytokines, abnormal kynurenine pathway and imbalance between neuroprotective and neurotoxic factors. Conclusions We found that stress-induced inflammation mediated by HMGB1 may affect motivational deficits through regulating dopamine pathway in corticostriatal neurocircuitry. The systematic review may shed light on the novel neurobiological underpinning for treatment of motivation deficits in depression.
基金Supported by the Zhejiang Natural Science Foundation of China,No.LGF18H030009.
文摘BACKGROUND Since December 2019,there have been many new cases of coronavirus pneumonia in Wuhan,Hubei Province,which has gradually spread throughout the country.AIM To explore our hospital’s innovative management system to ensure the efficient operation of fever clinics during the epidemic,since controlling the spread of disease is an important way to prevent and control the epidemic.METHODS In total,200 outpatients with fever at our hospital between November 2019 and July 2020 were selected and allocated into two groups.RESULTS The fever clinic in our hospital operated smoothly,and infection with the novel coronavirus disease(COVID-19)has not been reported in our hospital.Additionally,we did not have any cases of missed diagnosis.The awareness regarding COVID-19 infection sources,transmission routes,early symptoms,and preventive measures was significantly higher in our fever clinic than in those of the pre-management group.CONCLUSION"An integrated system,three separate responsibilities"ensured the efficient functioning of our fever outpatient clinic and early screening of COVID-19 cases,which effectively curbed the transmission of COVID-19 and hence prevented COVID-19 pneumonia epidemic in our hospital,ultimately achieving the maximum effect of epidemic prevention and control.
文摘Dear sir,Iam Dr.Wen-Wei Li,from the Department of Ophthalmology,Zhejiang Provincial People’s Hospital,Hangzhou,China.I write to present a case of ocular leech infestation initially misdiagnosed as conjunctival pigmented nevus.Although human interaction with leeches is not uncommon
基金supported by the Key Research and Development project of Zhejiang Province(2019C03039)Zhi-Ying Wu,National Key R&D Program of China(2018YFA0701400)to Hsin-Yi LaiSTI 2030-Major Projects(2021ZD0200401)to Anna Wang Roe.
文摘Huntington’s disease(HD)is an autosomal dominant neurodegenerative disease that is caused by a cytosine-adenine-guanine(CAG)expansion in the first exon of the huntingtin(HTT)gene,which codes for the hun-tingtin protein.It typically manifests with a triad of symptoms,including motor disorders,cognitive impair-ment and psychiatric disturbances[1].HD primar-ily affects the basal ganglia(BG),especially the caudate and putamen,after which it extends to more widespread gray and white matter[2].Perivascular spaces(PVSs)are fluid-filled extensions of the subarachnoid spaces that enclose cerebral blood vessels and extend from the cer-ebral cortex through the brain parenchyma.The physi-ological role of PVSs is the drainage of brain interstitial fluid into perivascular pathways for the elimination of waste products through the glymphatic drainage sys-tem.An increasing number of studies have demonstrated that enlarged PVSs indicate glymphatic dysfunction and are associated with many neurological diseases,such as Alzheimer’s disease,Parkinson’s disease and small vessel disease[3].With the advantage of strong field strengths,7.0 T images show superior resolution and signal-to-noise ratios than 3.0 T,which facilitate the visualization of PVS.And automated segmentation methods could accurately identify PVS in a short time with no inter-rater variability.In the current study,we used U-shaped networks(U-net),a class of deep learning methods,to explore the PVS distribution in HD and controls.To date,PVS distribution in HD is still unclear.Only two studies have investigated PVSs in HD,and both dem-onstrated increased visible PVS burden in manifest HD compared to controls[4,5].However,whether PVS bur-den increases in premanifest HD(pre-HD)individuals remains unknown,and the relationship of PVS with cog-nitive decline has never been studied.
基金JWV acknowledges funding from the NIH(T32MH019112)the SciLifeLab&Wallenberg Data Driven Life Science Program(Grant:KAW 2020.0239)+2 种基金Jeffrey S.Phillips was supported by NIH Grant(R01-AG054519,K01-AG061277)supported by NIH funding(P30 AG072979,P01AG066597,R01NS109260)Penn Institute on Aging,Robinson Family Fund,Peisach Family Fund for FTD Research,and Arking Family Fund.
文摘Background TDP-43 proteinopathies represent a spectrum of neurological disorders,anchored clinically on either end by amyotrophic lateral sclerosis(ALS)and frontotemporal degeneration(FTD).The ALS-FTD spectrum exhibits a diverse range of clinical presentations with overlapping phenotypes,highlighting its heterogeneity.This study was aimed to use disease progression modeling to identify novel data-driven spatial and temporal subtypes of brain atrophy and its progression in the ALS-FTD spectrum.Methods We used a data-driven procedure to identify 13 anatomic clusters of brain volume for 57 behavioral variant FTD(bvFTD;with either autopsy-confirmed TDP-43 or TDP-43 proteinopathy-associated genetic variants),103 ALS,and 47 ALS-FTD patients with likely TDP-43.A Subtype and Stage Inference(SuStaIn)model was trained to identify subtypes of individuals along the ALS-FTD spectrum with distinct brain atrophy patterns,and we related subtypes and stages to clinical,genetic,and neuropathological features of disease.Results SuStaIn identified three novel subtypes:two disease subtypes with predominant brain atrophy in either prefrontal/somatomotor regions or limbic-related regions,and a normal-appearing group without obvious brain atrophy.The limbic-predominant subtype tended to present with more impaired cognition,higher frequencies of pathogenic variants in TBK1 and TARDBP genes,and a higher proportion of TDP-43 types B,E and C.In contrast,the prefrontal/somatomotor-predominant subtype had higher frequencies of pathogenic variants in C9orf72 and GRN genes and higher proportion of TDP-43 type A.The normal-appearing brain group showed higher frequency of ALS relative to ALS-FTD and bvFTD patients,higher cognitive capacity,higher proportion of lower motor neuron onset,milder motor symptoms,and lower frequencies of genetic pathogenic variants.The overall SuStaIn stages also correlated with evidence for clinical progression including longer disease duration,higher King’s stage,and cognitive decline.Additionally,SuStaIn stages differed across clinical phenotypes,genotypes and types of TDP-43 pathology.Conclusions Our findings suggest distinct neurodegenerative subtypes of disease along the ALS-FTD spectrum that can be identified in vivo,each with distinct brain atrophy,clinical,genetic and pathological patterns.
