Since 2009,perovskite solar cells(PSCs)have advanced significantly,achieving over 26%efficiency for single-junction devices and exceeding 34%for silicon-perovskite tandem cells.Despite these successes,the weak adhesio...Since 2009,perovskite solar cells(PSCs)have advanced significantly,achieving over 26%efficiency for single-junction devices and exceeding 34%for silicon-perovskite tandem cells.Despite these successes,the weak adhesion of C_(60)to perovskite layers,due to van der Waals interactions,hinders long-term stability.In this study,we introduce electron-deficient intermolecular adhesives(EDIAs)as a novel interlayer material to enhance adhesion between perovskite and C_(60)layers.Comprehensive analyses,including density functional theory calculations,microscopy,and spectroscopy,demonstrate that EDIAs,particularly NDI-C9-Ace comprising of three key functionalities:aπ-electron-deficient arene core,a hydrophobic passivation core,and a secondary-bond anchoring core,significantly improve bonding strength and recombination passivation.This leads to enhanced efficiency as well as enhanced mechanical and photochemical stability in PSCs.Long-term stability tests further confirm the superior durability of EDIA-enhanced devices.This study highlights EDIA as a promising strategy for enhancing the robustness and efficiency of PSCs.展开更多
Background:Constitutional mismatch repair deficiency(CMMRD)is a rare disorder resulting from biallelic germline pathogenic variants in mismatch repair genes.This study described the molecular profile of two metachrono...Background:Constitutional mismatch repair deficiency(CMMRD)is a rare disorder resulting from biallelic germline pathogenic variants in mismatch repair genes.This study described the molecular profile of two metachronous brain tumors and a patient-derived xenograft(PDX)from a Brazilian child with CMMRD.Methods:After PDX development,methylation array,whole exome sequencing,and Nano String techniques were applied to describe the genetic landscape of CMMRD.Results:A 6½-year-old girl was diagnosed with Sonic Hedgehog(SHH)-activated medulloblastoma and somatic TP53-mutant.After surgery and radiochemotherapy,she remained free of disease progression.At 10 years and 3 months,she developed a diffuse pediatric-type high-grade glioma(dp HGG).The child had a family history of cancer,and subsequent investigation revealed a biallelic germline variant on MSH6(c.3556+1G>A)with the absence of protein expression in both normal and tumor tissue.A PDX model of the dp HGG was developed.The methylation profile confirmed the diagnosis of both brain tumors and PDX,refining the classification of dp HGG,Rtk1 subtype,subclass A,with an actionable alteration on Platelet-derived growth factor receptor A(PDGFRA).Exome analysis showed high tumor mutational burden,with 3019,540,and 1049 pathogenic variants in the medulloblastoma,dp HGG,and PDX,respectively.Only the medulloblastoma exhibited microsatellite instability.The CD24,CD47,and CD276 immune checkpoints had elevated messenger RNA levels,yet no programmed death ligand 1 expression was observed in CMMRD-derived tumors.Conclusion:We report an extensive molecular profile of a CMMRD patient,and the developed PDX model can be applied to explore new therapeutic approaches for CMMRD-associated brain tumors.展开更多
Adult neurogenesis continuously produces new neurons critical for cognitive plasticity in adult rodents.While it is known transforming growth factor-βsignaling is important in embryonic neurogenesis,its role in postn...Adult neurogenesis continuously produces new neurons critical for cognitive plasticity in adult rodents.While it is known transforming growth factor-βsignaling is important in embryonic neurogenesis,its role in postnatal neurogenesis remains unclear.In this study,to define the precise role of transforming growth factor-βsignaling in postnatal neurogenesis at distinct stages of the neurogenic cascade both in vitro and in vivo,we developed two novel inducible and cell type-specific mouse models to specifically silence transforming growth factor-βsignaling in neural stem cells in(mGFAPcre-ALK5fl/fl-Ai9)or immature neuroblasts in(DCXcreERT2-ALK5fl/fl-Ai9).Our data showed that exogenous transforming growth factor-βtreatment led to inhibition of the proliferation of primary neural stem cells while stimulating their migration.These effects were abolished in activin-like kinase 5(ALK5)knockout primary neural stem cells.Consistent with this,inhibition of transforming growth factor-βsignaling with SB-431542 in wild-type neural stem cells stimulated proliferation while inhibited the migration of neural stem cells.Interestingly,deletion of transforming growth factor-βreceptor in neural stem cells in vivo inhibited the migration of postnatal born neurons in mGFAPcre-ALK5fl/fl-Ai9 mice,while abolishment of transforming growth factor-βsignaling in immature neuroblasts in DCXcreERT2-ALK5fl/fl-Ai9 mice did not affect the migration of these cells in the hippocampus.In summary,our data supports a dual role of transforming growth factor-βsignaling in the proliferation and migration of neural stem cells in vitro.Moreover,our data provides novel insights on cell type-specific-dependent requirements of transforming growth factor-βsignaling on neural stem cell proliferation and migration in vivo.展开更多
The lysosomal enzyme β-glucocerebrosidase(GCase) belongs to the family of glycosidases and hydrolyses the glycosphingolipid glucosylceramide(GluCer) into glucose and ceramide. The enzyme is of central importance for ...The lysosomal enzyme β-glucocerebrosidase(GCase) belongs to the family of glycosidases and hydrolyses the glycosphingolipid glucosylceramide(GluCer) into glucose and ceramide. The enzyme is of central importance for two pathologies:(1) the lysosomal storage disorder Gaucher's disease(GD) and(2) the neurodegenerative disorder Parkinson's disease(PD).展开更多
The growing global energy demand and worsening climate change highlight the urgent need for clean,efficient and sustainable energy solutions.Among emerging technologies,atomically thin two-dimensional(2D)materials off...The growing global energy demand and worsening climate change highlight the urgent need for clean,efficient and sustainable energy solutions.Among emerging technologies,atomically thin two-dimensional(2D)materials offer unique advantages in photovoltaics due to their tunable optoelectronic properties,high surface area and efficient charge transport capabilities.This review explores recent progress in photovoltaics incorporating 2D materials,focusing on their application as hole and electron transport layers to optimize bandgap alignment,enhance carrier mobility and improve chemical stability.A comprehensive analysis is presented on perovskite solar cells utilizing 2D materials,with a particular focus on strategies to enhance crystallization,passivate defects and improve overall cell efficiency.Additionally,the application of 2D materials in organic solar cells is examined,particularly for reducing recombination losses and enhancing charge extraction through work function modification.Their impact on dye-sensitized solar cells,including catalytic activity and counter electrode performance,is also explored.Finally,the review outlines key challenges,material limitations and performance metrics,offering insight into the future development of nextgeneration photovoltaic devices encouraged by 2D materials.展开更多
The human intestinal microbiome plays a major role in human health and diseases, including colorectal cancer. Colorectal carcinogenesis represents a heterogeneous process with a differing set of somatic molecular alte...The human intestinal microbiome plays a major role in human health and diseases, including colorectal cancer. Colorectal carcinogenesis represents a heterogeneous process with a differing set of somatic molecular alterations, influenced by diet, environmental and microbial exposures, and host immunity. Fusobacterium species are part of the human oral and intestinal microbiota. Metagenomic analyses have shown an enrichment of Fusobacterium nucleatum(F. nucleatum) in colorectal carcinoma tissue. Using 511 colorectal carcinomas from Japanese patients, we assessed the presence of F. nucleatum. Our results showed that the frequency of F. nucleatum positivity in the Japanese colorectal cancer was 8.6%(44/511), which was lower than that in United States cohort studies(13%). Similar to the United States studies, F. nucleatum positivityin Japanese colorectal cancers was significantly associated with microsatellite instability(MSI)-high status. Regarding the immune response in colorectal cancer, high levels of infiltrating T-cell subsets(i.e., CD3+, CD8+, CD45RO+, and FOXP3+ cells) have been associated with better patient prognosis. There is also evidence to indicate that molecular features of colorectal cancer, especially MSI, influence T-cell-mediated adaptive immunity. Concerning the association between the gut microbiome and immunity, F. nucleatum has been shown to expand myeloid-derived immune cells, which inhibit T-cell proliferation and induce T-cell apoptosis in colorectal cancer. This finding indicates that F. nucleatum possesses immunosuppressive activities by inhibiting human T-cell responses. Certain micro RNAs are induced during the macrophage inflammatory response and have the ability to regulate host-cell responses to pathogens. Micro RNA-21 increases the levels of IL-10 and prostaglandin E2, which suppress antitumor T-cell-mediated adaptive immunity through the inhibition of the antigen-presenting capacities of dendritic cells and T-cell proliferation in colorectal cancer cells. Thus, emerging evidence may provide insights for strategies to target microbiota, immune cells and tumor molecular alterations for colorectal cancer prevention and treatment. Further investigation is needed to clarify the association of Fusobacterium with T-cells and micro RNA expressions in colorectal cancer.展开更多
Rice grows in flooded paddy fields and takes up ammonium as the preferred nitrogen （N） source. Ammonium uptake is facilitated by a family of integral membrane proteins known as ammonium transporters found in all dom...Rice grows in flooded paddy fields and takes up ammonium as the preferred nitrogen （N） source. Ammonium uptake is facilitated by a family of integral membrane proteins known as ammonium transporters found in all domains of life. However, the molecular mechanism and functional characteristics of the ammonium transporters （AMT） in rice have not been determined in detail yet. In this review, we report a genome-wide search for AMT genes in rice, resulting in the increase of the number of potential AMT proteins to at least 12, including members of both the alpha and beta sub-groups. Analysis of the predicted protein sequences for the 12 OsAMT proteins identified many conserved phosphorylation sites in both the alpha and beta group members, which could potentially play a role in controlling the activity of the transporters. Present knowledge of the expression of rice AMT genes is also summarized in detail. Future studies should focus on the structural and functional characteristics of OsAMT proteins to provide insight into the mechanism of ammonium uptake and its regulation in rice. Such research could improve utilization and decrease wastage of N fertilizer in rice cultivation.展开更多
In recent years, the improvement of technology and the increase in knowledge have shifted several strongly held paradigms. This is particularly true in gastroenterology, and specifically in the field of the so-called ...In recent years, the improvement of technology and the increase in knowledge have shifted several strongly held paradigms. This is particularly true in gastroenterology, and specifically in the field of the so-called "functional" or "idiopathic" disease, where conditions thought for decades to be based mainly on alterations of visceral perception or aberrant psychosomatic mechanisms have, in fact, be reconducted to an organic basis (or, at the very least, have shown one or more demonstrable abnormalities). This is particularly true, for instance, for irritable bowel syndrome, the prototype entity of "functional" gastrointestinal disorders, where low-grade inflammation of both mucosa and myenteric plexus has been repeatedly demonstrated. Thus, researchers have also investigated other functional/idiopathic gastrointestinal disorders, and found that some organic ground is present, such as abnormal neurotransmission and myenteric plexitis in esophageal achalasia and mucosal immune activation and mild eosinophilia in functional dyspepsia. Here we show evidence, based on our own and other authors' work, that chronic constipation has several abnormalities reconductable to alterations in the enteric nervous system, abnormalities mainly characterized by a constant decrease of enteric glial cells and interstitial cells of Cajal (and, sometimes, of enteric neurons). Thus, we feel that (at least some forms of) chronic constipation should no more be considered as a functional/idiopathic gastrointestinal disorder, but instead as a true enteric neuropathic abnormality.展开更多
The clinical course of infections with the hepatitis B virus (HBV) substantially varies between individuals, as a consequence of a complex interplay between viral, host, environmental and other factors. Due to the hig...The clinical course of infections with the hepatitis B virus (HBV) substantially varies between individuals, as a consequence of a complex interplay between viral, host, environmental and other factors. Due to the high genetic variability of HBV, the virus can be categorized into different HBV genotypes and subgenotypes, which considerably differ with respect to geographical distribution, transmission routes, disease progression, responses to antiviral therapy or vaccination, and clinical outcome measures such as cirrhosis or hepatocellular carcinoma. However, HBV (sub)genotyping has caused some controversies in the past due to misclassifications and incorrect interpretations of different genotyping methods. Thus, an accurate, holistic and dynamic classification system is essential. In this review article, we aimed at highlighting potential pitfalls in genetic and phylogenetic analyses of HBV and suggest novel terms for HBV classification. Analyzing full-length genome sequences when classifying genotypes and subgenotypes is the foremost prerequisite of this classification system. Careful attention must be paid to all aspects of phylogenetic analysis, such as bootstrapping values and meeting the necessary thresholds for (sub)genotyping. Quasi-subgenotype refers to subgenotypes that were incorrectly suggested to be novel. As many of these strains were misclassified due to genetic differences resulting from recombination, we propose the term “recombino-subgenotype”. Moreover, immigration is an important confounding facet of global HBV distribution and substantially changes the geographic pattern of HBV (sub)genotypes. We therefore suggest the term “immigro-subgenotype” to distinguish exotic (sub)genotypes from native ones. We are strongly convinced that applying these two proposed terms in HBV classification will help harmonize this rapidly progressing field and allow for improved prophylaxis, diagnosis and treatment.展开更多
Pyricularia oryzae anamorph of Magnaporthe oryzae is one of the most notorious fungal pathogens causing severe economic loss in rice production worldwide. Various methods, viz. cultural, biological and molecular appro...Pyricularia oryzae anamorph of Magnaporthe oryzae is one of the most notorious fungal pathogens causing severe economic loss in rice production worldwide. Various methods, viz. cultural, biological and molecular approaches, are utilized to counteract this pathogen. Moreover, some tolerant or resistant rice varieties have been developed with the help of breeding programmes. Isolation and molecular characterization of different blast resistance genes now open the gate for new possibilities to elucidate the actual allelic variants of these genes via various molecular breeding and transgenic approaches. However, the behavioral pattern of this fungus breakups the resistance barriers in the resistant or tolerant rice varieties. This host-pathogen barrier will be possibly countered in future research by comparative genomics data from available genome sequence data of rice and M. oryzae for durable resistance. Present review emphasized fascinating recent updates, new molecular breeding approaches, transgenic and genomics approaches(i.e. mi RNA and genome editing) for the management of blast disease in rice. The updated information will be helpful for the durable, resistance breeding programme in rice against blast pathogen.展开更多
AIM:To investigate molecular phenotypes of myocardial B19V-infection to determine the role of B19V in myocarditis and dilated cardiomyopathy(DCM).METHODS:Endomyocardial biopsies(EMBs) from 498 B19V-positive patients w...AIM:To investigate molecular phenotypes of myocardial B19V-infection to determine the role of B19V in myocarditis and dilated cardiomyopathy(DCM).METHODS:Endomyocardial biopsies(EMBs) from 498 B19V-positive patients with myocarditis and DCMwere analyzed using molecular methods and functional experiments.EMBs were obtained from the University Hospitals of Greifswald and Tuebingen and additionally from 36 German cardiology centers.Control tissues were obtained at autopsy from 34 victims of accidents,crime or suicide.Identification of mononuclear cell infiltrates in EMBs was performed using immunohistological staining.Anti-B19V-IgM and anti-B19V-IgG were analyzed by enzyme-linked immunosorbent assay(ELISA).B19V viral loads were determined using in-house quantitative real-time polymerase chain reaction(PCR).For B19V-genotyping a new B19V-genotype-specific restriction fragment length polymorphism(RFLP)-PCR was established.B19V-genotyping was verified by direct DNAsequencing and sequences were aligned using BLAST and BioEdit software.B19V P6-promoter and HHV6-U94-transactivator constructs were generated for cell culture experiments.Transfection experiments were conducted using human endothelial cells 1.Luciferase reporter assays were performed to determine B19Vreplication activity.Statistical analysis and graphical representation were calculated using SPSS and Prism5 software.RESULTS:The prevalence of B19V was significantly more likely to be associated with inflammatory cardiomyopathy(iCMP) compared to uninflamed DCM(59.6% vs 35.3%)(P < 0.0001).The detection of B19V-mRNA replication intermediates proved that replication of B19V was present.RFLP-PCR assays showed that B19V-genotype 1(57.4%) and B19V-genotype 2(36.7%) were the most prevalent viral genotypes.B19V-genotype 2 was observed more frequently in EMBs with iCMP(65.0%) compared to DCM(35%)(P = 0.049).Although there was no significant difference in gender-specific B19V-loads,women were more frequently infected with B19V-genotype 2(44.6%) than men(36.0%)(P = 0.0448).Coinfection with B19V and other cardiotropic viruses was found in 19.2% of tissuesamples and was associated with higher B19V viral load compared to B19V-monoinfected tissue(P = 0.0012).The most frequent coinfecting virus was human herpes virus 6(HHV6,16.5%).B19V-coinfection with HHV6 showed higher B19V-loads compared to B19V-monoinfected EMBs(P = 0.0033),suggesting that HHV6 had transactivated B19V.In vitro experiments confirmed a 2.4-fold increased B19V P6-promoter activity by the HHV6 U94-transactivator.CONCLUSION:The finding of significantly increased B19V loads in patients with histologically proven cardiac inflammation suggests a crucial role of B19V-genotypes and reactivation of B19V-infection by HHV6-coinfection in B19V-associated iCMP.Our findings suggest that B19V-infection of the human heart can be a causative event for the development of an endothelial cell-mediated inflammatory disease and that this is related to both viral load and genotype.展开更多
Objective:We aimed to summarize the clinicopathological characteristics and prognostic features of various molecular subtypes of diffuse gliomas(DGs)in the Chinese population.Methods:In total,1,418 patients diagnosed ...Objective:We aimed to summarize the clinicopathological characteristics and prognostic features of various molecular subtypes of diffuse gliomas(DGs)in the Chinese population.Methods:In total,1,418 patients diagnosed with DG between 2011 and 2017 were classified into 5 molecular subtypes according to the 2016 WHO classification of central nervous system tumors.The IDH mutation status was determined by immunohistochemistry and/or DNA sequencing,and 1p/19q codeletion was detected with fluorescence in situ hybridization.The median clinical follow-up time was 1,076 days.T-tests and chi-square tests were used to compare clinicopathological characteristics.Kaplan‒Meier and Cox regression methods were used to evaluate prognostic factors.Results:Our cohort included 15.5%lower-grade gliomas,IDH-mutant and 1p/19q-codeleted(LGG-IDHm-1p/19q);18.1%lowergrade gliomas,IDH-mutant(LGG-IDHm);13.1%lower-grade gliomas,IDH-wildtype(LGG-IDHwt);36.1%glioblastoma,IDHwildtype(GBM-IDHwt);and 17.2%glioblastoma,IDH-mutant(GBM-IDHm).Approximately 63.3%of the enrolled primary gliomas,and the median overall survival times for LGG-IDHm,LGG-IDHwt,GBM-IDHwt,and GBM-IDHm subtypes were 75.97,34.47,11.57,and 15.17 months,respectively.The 5-year survival rate of LGG-IDHm-1p/19q was 76.54%.We observed a significant association between high resection rate and favorable survival outcomes across all subtypes of primary tumors.We also observed a significant role of chemotherapy in prolonging overall survival for GBM-IDHwt and GBM-IDHm,and in prolonging post-relapse survival for the 2 recurrent GBM subtypes.Conclusions:By controlling for molecular subtypes,we found that resection rate and chemotherapy were 2 prognostic factors associated with survival outcomes in a Chinese cohort with DG.展开更多
Osteogenesis imperfecta（OI,also known as brittle bone disease）is caused mostly by mutations in two type I collagen genes,COL1A1 and COLIA2 encoding the pro-α1（I）and pro-α2（I）chains of type I collagen,respectiv...Osteogenesis imperfecta（OI,also known as brittle bone disease）is caused mostly by mutations in two type I collagen genes,COL1A1 and COLIA2 encoding the pro-α1（I）and pro-α2（I）chains of type I collagen,respectively.Two Chinese families with autosomal dominant OI were identified and characterized.Linkage analysis revealed linkage of both families to COL1A2 on chromosome 7q21.3-q22.1.Mutational analysis was carried out using direct DNA sequence analysis.Two novel missense mutations,c.3350AG and c.3305GC,were identified in exon 49 of COL1A2 in the two families,respectively.The c.3305GC mutation resulted in substitution of a glycine residue（G）by an alanine residue（A）at codon 1102（p.G1102A）,which was found to be mutated into serine（S）,argine（R）,aspartic acid（D）,or valine（V）in other families.The c.3350AG variant may be a de novo mutation resulting in p.Y1117C.Both mutations co-segregated with OI in respective families,and were not found in 100 normal controls.The G1102 and Y1117 residues were evolutionarily highly conserved from zebrafish to humans.Mutational analysis did not identify any mutation in the COX-2 gene（a modifier gene of OI）.This study identifies two novel mutations p.G1102A and p.Y1117C that cause OI,significantly expands the spectrum of COL1A2 mutations causing OI,and has a significant implication in prenatal diagnosis of OI.展开更多
Positron emission tomography measures the activity of radioactively labeled compounds which distribute and accumulate in central nervous system regions in proportion to their metabolic rate or blood flow. Specific cir...Positron emission tomography measures the activity of radioactively labeled compounds which distribute and accumulate in central nervous system regions in proportion to their metabolic rate or blood flow. Specific circuits such as the dopaminergic nigrostriatal projection can be studied with ligands that bind to the pre-synaptic dopamine transporter or post-synaptic dopamine receptors (D1 and D2). Single photon emission computerized tomography (SPECT) measures the activity of similar tracers labeled with heavy radioactive species such as technetium and iodine. In essential tremor, there is cerebellar hypermetabolism and abnormal GABAergic function in premotor cortices, dentate nuclei and ventral thalami, without significant abnormalities in dopaminergic transmission. In Huntington’s disease, there is hypometabolism in the striatum, frontal and temporal cortices. Disease progression is accompanied by reduction in striatal D1 and D2 binding that correlates with trinucleotide repeat length, disease duration and severity. In dystonia, there is hypermetabolism in the basal ganglia, supplementary motor areas and cerebellum at rest. Thalamic and cerebellar hypermetabolism is seen during dystonic movements, which can be modulated by globus pallidus deep brain stimulation (DBS). Additionally, GABA-A receptor activity is reduced in motor, premotor and somatosensory cortices. In Tourette’s syndrome, there is hypermetabolism in premotor and sensorimotor cortices, as well as hypometabolism in the striatum, thalamus and limbic regions at rest. During tics, multiple areas related to cognitive, sensory and motor functions become hypermetabolic. Also, there is abnormal serotoninergic transmission in prefrontal cortices and bilateral thalami, as well as hyperactivity in the striatal dopaminergic system which can be modulated with thalamic DBS. In Parkinson’s disease (PD), there is asymmetric progressive decline in striatal dopaminergic tracer accumulation, which follows a caudal-to-rostral direction. Uptake declines prior to symptom presentation and progresses from contralateral to the most symptomatic side to bilateral, correlating with symptom severity. In progressive supranuclear palsy (PSP) and multiple system atrophy (MSA), striatal activity is symmetrically and diffusely decreased. The caudal-to-rostral pattern is lost in PSP, but could be present in MSA. In corticobasal degeneration (CBD), there is asymmetric, diffuse reduction of striatal activity, contralateral to the most symptomatic side. Additionally, there is hypometabolism in contralateral parieto-occipital and frontal cortices in PD; bilateral putamen and cerebellum in MSA; caudate, thalamus, midbrain, mesial frontal and prefrontal cortices in PSP; and contralateral cortices in CBD. Finally, cardiac sympathetic SPECT signal is decreased in PD. The capacity of molecular imaging to provide in vivo time courses of gene expression, protein synthesis, receptor and transporter binding, could facilitate the development and evaluation of novel medical, surgical and genetic therapies in movement disorders.展开更多
Precision medicine and personalized therapy are receiving increased attention, and molecular-subtype classification has become crucial in planning therapeutic schedules in clinical practice for patients with breast ca...Precision medicine and personalized therapy are receiving increased attention, and molecular-subtype classification has become crucial in planning therapeutic schedules in clinical practice for patients with breast cancer. Human epidermal growth factor receptor 2(HER2) is associated with high-grade breast tumors, high rates of lymph-node involvement, high risk of recurrence, and high resistance to general chemotherapy. Analysis of HER2 expression is highly important for doctors to identify patients who can benefit from trastuzumab therapy and monitor the response and efficacy of treatment. In recent years, significant efforts have been devoted to achieving specific and noninvasive HER2-positive breast cancer imaging in vivo. In this work, we reviewed existing literature on HER2 imaging in the past decade and summarized the studies from different points of view, such as imaging modalities and HER2-specific probes. We aimed to improve the understanding on the translational process in molecular imaging for HER2 breast cancer.展开更多
Cleft palate, including complete or incomplete cleft palates, soft palate clefts, and submucosal cleft palates, is the most frequent congenital craniofacial anomaly in humans. Multifactorial conditions, including gene...Cleft palate, including complete or incomplete cleft palates, soft palate clefts, and submucosal cleft palates, is the most frequent congenital craniofacial anomaly in humans. Multifactorial conditions, including genetic and environmental factors, induce the formation of cleft palates. The process of palatogenesis is temporospatially regulated by transcription factors, growth factors, extracellular matrix proteins, and membranous molecules; a single ablation of these molecules can result in a cleft palate in vivo. Studies on knockout mice were reviewed in order to identify genetic errors that lead to cleft palates. In this review, we systematically describe these mutant mice and discuss the molecular mechanisms of palatogenesis.展开更多
Uniform molecular weight(Mw)chitosan(CS)is highly demanded in medical biomaterial industry.This present article described heterogeneous degradation of CS in aqueous HCl/ethanol solution,in which progress uniform Mw CS...Uniform molecular weight(Mw)chitosan(CS)is highly demanded in medical biomaterial industry.This present article described heterogeneous degradation of CS in aqueous HCl/ethanol solution,in which progress uniform Mw CS was successfully prepared.The Mw distribution of CS was measured by gel permeation chromatography(GPC)analysis.Moreover,the structure and properties of degraded CS were characterized by Fourier transform infrared spectroscopy(FT-IR),nuclear magnetic resonance spectroscopy(^1H NMR),X-ray diffraction(XRD)and thermogravimetric(TG)analysis.In addition,the biocompatibility of degraded CS was also assessed by hemolysis rate(HR)measurement.The Mw of CS dramatically decreased from 246 KDa to 76 k Da at the initial 30 min,and stabilized at 18 kDa after 24 h.GPC analysis results showed that the degraded CS molecular become homogenization.FT-IR and 1 H NMR analysis confirmed the basic structure of CS molecular backbone was not destroyed during this progress.Besides,the water solubility of CS was not significantly influenced by this reaction.Moreover,the XRD analysis revealed that crystallinity of degraded CS increased from 70.32% to 99.25%with time.The TG analysis showed improved thermal stability of degraded CS.HR measurement demonstrated the degraded CS possessed excellent biocompatibility.This simple and efficient heterogeneous degradation would open up a new route to produce uniform Mw CS.展开更多
Wiedemann-Steiner syndrome(OMIM#605130)is a rare congenital malformation syndrome characterized by hypertrichosis cubiti associated with short stature;consistent facial features,including long eyelashes,thick or arche...Wiedemann-Steiner syndrome(OMIM#605130)is a rare congenital malformation syndrome characterized by hypertrichosis cubiti associated with short stature;consistent facial features,including long eyelashes,thick or arched eyebrows with a lateral flare,wide nasal bridge,and downslanting and vertically narrow palpebral fissures;mild to moderate intellectual disability;behavioral difficulties;and hypertrichosis on the back.It is caused by heterozygous pathogenic variants in KMT2A.This gene has an established role in histone methylation,which explains the overlap of Wiedemann-Steiner syndrome with other chromatinopathies,a heterogeneous group of syndromic conditions that share a common trigger:The disruption of one of the genes involved in chromatin modification,leading to dysfunction of the epigenetic machinery.展开更多
The molecular chaperone HSP60 is a chaperonin homolog of GroEL. We had previously shown that the immunosuppressant mizoribine is bound directly to HSP60 and inhibited its chaperone activity. However, the inhibitory me...The molecular chaperone HSP60 is a chaperonin homolog of GroEL. We had previously shown that the immunosuppressant mizoribine is bound directly to HSP60 and inhibited its chaperone activity. However, the inhibitory mechanisms of HSP60 by mizoribine have not yet been fully understood. In the present study, we investigated the influence of mizoribine on a folding cycle of HSP60 and co-chaperone HSP10. Our results showed that mizoribine inhibited the folding cycle of HSP60/HSP10. The ATPase activity of HSP60/HSP10 was decreased in the presence of mizoribine and the dissociation of HSP10 from HSP-60 was also decreased by mizoribine. The same functions of GroEL and/or GroES were slightly affected by mizoribine. Based on our findings, we discuss the inhibitory mechanisms of HSP60 by mizoribine.展开更多
The unique physicochemical properties inherent to nanoscale materials have unveiled numerous potential applications,spanning beyond the pharmaceutical and medical sectors into various consumer industries like food and...The unique physicochemical properties inherent to nanoscale materials have unveiled numerous potential applications,spanning beyond the pharmaceutical and medical sectors into various consumer industries like food and cosmetics.Consequently,humans encounter nanomaterials through diverse exposure routes,giving rise to potential health considerations.Noteworthy among these materials are silica and specific metallic nanoparticles,extensively utilized in consumer products,which have garnered substantial attention due to their propensity to accumulate and induce adverse effects in the liver.This review paper aims to provide an exhaustive examination of the molecular mechanisms underpinning nanomaterial-induced hepatotoxicity,drawing insights from both in vitro and in vivo studies.Primarily,the most frequently observed manifestations of toxicity following the exposure of cells or animal models to various nanomaterials involve the initiation of oxidative stress and inflammation.Additionally,we delve into the existing in vitro models employed for evaluating the hepatotoxic effects of nanomaterials,emphasizing the persistent endeavors to advance and bolster the reliability of these models for nanotoxicology research.展开更多
基金supported by National Research Foundation of Korea(NRF)(RS-2024-00336766 and RS-2023-00301974)support of the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(RS-2023-00220748)。
文摘Since 2009,perovskite solar cells(PSCs)have advanced significantly,achieving over 26%efficiency for single-junction devices and exceeding 34%for silicon-perovskite tandem cells.Despite these successes,the weak adhesion of C_(60)to perovskite layers,due to van der Waals interactions,hinders long-term stability.In this study,we introduce electron-deficient intermolecular adhesives(EDIAs)as a novel interlayer material to enhance adhesion between perovskite and C_(60)layers.Comprehensive analyses,including density functional theory calculations,microscopy,and spectroscopy,demonstrate that EDIAs,particularly NDI-C9-Ace comprising of three key functionalities:aπ-electron-deficient arene core,a hydrophobic passivation core,and a secondary-bond anchoring core,significantly improve bonding strength and recombination passivation.This leads to enhanced efficiency as well as enhanced mechanical and photochemical stability in PSCs.Long-term stability tests further confirm the superior durability of EDIA-enhanced devices.This study highlights EDIA as a promising strategy for enhancing the robustness and efficiency of PSCs.
基金Brazilian National Program of Genomics and Precision Health-Genomas Brasil,Grant/Award Number:MS-SECTICS-Decit/CNPq 16/2023São Paulo Research Foundation,Grant/Award Number:FAPESP-2021/07957-5+5 种基金Barretos Cancer Hospital,Grant/Award Number:13/2021National Oncology Care Support Program (PRONON),CNPq,Grant/Award Number:444217/2023-1Public Ministry of Labor Campinas (Research, Prevention, and Education of Occupational Cancer)Brazilian Ministry of Health (MoH)National Council for Scientific and Technological DevelopmentCNPq Productivity
文摘Background:Constitutional mismatch repair deficiency(CMMRD)is a rare disorder resulting from biallelic germline pathogenic variants in mismatch repair genes.This study described the molecular profile of two metachronous brain tumors and a patient-derived xenograft(PDX)from a Brazilian child with CMMRD.Methods:After PDX development,methylation array,whole exome sequencing,and Nano String techniques were applied to describe the genetic landscape of CMMRD.Results:A 6½-year-old girl was diagnosed with Sonic Hedgehog(SHH)-activated medulloblastoma and somatic TP53-mutant.After surgery and radiochemotherapy,she remained free of disease progression.At 10 years and 3 months,she developed a diffuse pediatric-type high-grade glioma(dp HGG).The child had a family history of cancer,and subsequent investigation revealed a biallelic germline variant on MSH6(c.3556+1G>A)with the absence of protein expression in both normal and tumor tissue.A PDX model of the dp HGG was developed.The methylation profile confirmed the diagnosis of both brain tumors and PDX,refining the classification of dp HGG,Rtk1 subtype,subclass A,with an actionable alteration on Platelet-derived growth factor receptor A(PDGFRA).Exome analysis showed high tumor mutational burden,with 3019,540,and 1049 pathogenic variants in the medulloblastoma,dp HGG,and PDX,respectively.Only the medulloblastoma exhibited microsatellite instability.The CD24,CD47,and CD276 immune checkpoints had elevated messenger RNA levels,yet no programmed death ligand 1 expression was observed in CMMRD-derived tumors.Conclusion:We report an extensive molecular profile of a CMMRD patient,and the developed PDX model can be applied to explore new therapeutic approaches for CMMRD-associated brain tumors.
基金supported by NIH grants,Nos.R01NS125074,R01AG083164,R01NS107365,and R21NS127177(to YL),1F31NS129204-01A1(to KW)and Albert Ryan Fellowship(to KW).
文摘Adult neurogenesis continuously produces new neurons critical for cognitive plasticity in adult rodents.While it is known transforming growth factor-βsignaling is important in embryonic neurogenesis,its role in postnatal neurogenesis remains unclear.In this study,to define the precise role of transforming growth factor-βsignaling in postnatal neurogenesis at distinct stages of the neurogenic cascade both in vitro and in vivo,we developed two novel inducible and cell type-specific mouse models to specifically silence transforming growth factor-βsignaling in neural stem cells in(mGFAPcre-ALK5fl/fl-Ai9)or immature neuroblasts in(DCXcreERT2-ALK5fl/fl-Ai9).Our data showed that exogenous transforming growth factor-βtreatment led to inhibition of the proliferation of primary neural stem cells while stimulating their migration.These effects were abolished in activin-like kinase 5(ALK5)knockout primary neural stem cells.Consistent with this,inhibition of transforming growth factor-βsignaling with SB-431542 in wild-type neural stem cells stimulated proliferation while inhibited the migration of neural stem cells.Interestingly,deletion of transforming growth factor-βreceptor in neural stem cells in vivo inhibited the migration of postnatal born neurons in mGFAPcre-ALK5fl/fl-Ai9 mice,while abolishment of transforming growth factor-βsignaling in immature neuroblasts in DCXcreERT2-ALK5fl/fl-Ai9 mice did not affect the migration of these cells in the hippocampus.In summary,our data supports a dual role of transforming growth factor-βsignaling in the proliferation and migration of neural stem cells in vitro.Moreover,our data provides novel insights on cell type-specific-dependent requirements of transforming growth factor-βsignaling on neural stem cell proliferation and migration in vivo.
基金supported by the Michael J Fox Foundation (to PA and FZ)。
文摘The lysosomal enzyme β-glucocerebrosidase(GCase) belongs to the family of glycosidases and hydrolyses the glycosphingolipid glucosylceramide(GluCer) into glucose and ceramide. The enzyme is of central importance for two pathologies:(1) the lysosomal storage disorder Gaucher's disease(GD) and(2) the neurodegenerative disorder Parkinson's disease(PD).
基金supported by the IITP(Institute of Information & Communications Technology Planning & Evaluation)-ITRC(Information Technology Research Center) grant funded by the Korea government(Ministry of Science and ICT) (IITP-2025-RS-2024-00437191, and RS-2025-02303505)partly supported by the Korea Basic Science Institute (National Research Facilities and Equipment Center) grant funded by the Ministry of Education. (No. 2022R1A6C101A774)the Deanship of Research and Graduate Studies at King Khalid University, Saudi Arabia, through Large Research Project under grant number RGP-2/527/46
文摘The growing global energy demand and worsening climate change highlight the urgent need for clean,efficient and sustainable energy solutions.Among emerging technologies,atomically thin two-dimensional(2D)materials offer unique advantages in photovoltaics due to their tunable optoelectronic properties,high surface area and efficient charge transport capabilities.This review explores recent progress in photovoltaics incorporating 2D materials,focusing on their application as hole and electron transport layers to optimize bandgap alignment,enhance carrier mobility and improve chemical stability.A comprehensive analysis is presented on perovskite solar cells utilizing 2D materials,with a particular focus on strategies to enhance crystallization,passivate defects and improve overall cell efficiency.Additionally,the application of 2D materials in organic solar cells is examined,particularly for reducing recombination losses and enhancing charge extraction through work function modification.Their impact on dye-sensitized solar cells,including catalytic activity and counter electrode performance,is also explored.Finally,the review outlines key challenges,material limitations and performance metrics,offering insight into the future development of nextgeneration photovoltaic devices encouraged by 2D materials.
基金Supported by Japanese Society of Gastroenterology Research Foundation(to Nosho K)Pancreas Research Foundation of Japan(to Nosho K)+4 种基金Medical Research Encouragement Prize of The Japan Medical Association(to Nosho K)The Japan Society for the Promotion of Science Challenging Exploratory Researchgrant No.25670371(to Shinomura Y)Ono Cancer Research Foundation(to Ito M)
文摘The human intestinal microbiome plays a major role in human health and diseases, including colorectal cancer. Colorectal carcinogenesis represents a heterogeneous process with a differing set of somatic molecular alterations, influenced by diet, environmental and microbial exposures, and host immunity. Fusobacterium species are part of the human oral and intestinal microbiota. Metagenomic analyses have shown an enrichment of Fusobacterium nucleatum(F. nucleatum) in colorectal carcinoma tissue. Using 511 colorectal carcinomas from Japanese patients, we assessed the presence of F. nucleatum. Our results showed that the frequency of F. nucleatum positivity in the Japanese colorectal cancer was 8.6%(44/511), which was lower than that in United States cohort studies(13%). Similar to the United States studies, F. nucleatum positivityin Japanese colorectal cancers was significantly associated with microsatellite instability(MSI)-high status. Regarding the immune response in colorectal cancer, high levels of infiltrating T-cell subsets(i.e., CD3+, CD8+, CD45RO+, and FOXP3+ cells) have been associated with better patient prognosis. There is also evidence to indicate that molecular features of colorectal cancer, especially MSI, influence T-cell-mediated adaptive immunity. Concerning the association between the gut microbiome and immunity, F. nucleatum has been shown to expand myeloid-derived immune cells, which inhibit T-cell proliferation and induce T-cell apoptosis in colorectal cancer. This finding indicates that F. nucleatum possesses immunosuppressive activities by inhibiting human T-cell responses. Certain micro RNAs are induced during the macrophage inflammatory response and have the ability to regulate host-cell responses to pathogens. Micro RNA-21 increases the levels of IL-10 and prostaglandin E2, which suppress antitumor T-cell-mediated adaptive immunity through the inhibition of the antigen-presenting capacities of dendritic cells and T-cell proliferation in colorectal cancer cells. Thus, emerging evidence may provide insights for strategies to target microbiota, immune cells and tumor molecular alterations for colorectal cancer prevention and treatment. Further investigation is needed to clarify the association of Fusobacterium with T-cells and micro RNA expressions in colorectal cancer.
基金supported by the China Postdoctoral Science Foundation (Grant No. 20070421031)the National Basic Research Program of China (Grant No. 2007CB109303)Knowledge Innovation Project of the Chinese Academy of Sciences (Grant No. KSCX2-YW-N-002)
文摘Rice grows in flooded paddy fields and takes up ammonium as the preferred nitrogen （N） source. Ammonium uptake is facilitated by a family of integral membrane proteins known as ammonium transporters found in all domains of life. However, the molecular mechanism and functional characteristics of the ammonium transporters （AMT） in rice have not been determined in detail yet. In this review, we report a genome-wide search for AMT genes in rice, resulting in the increase of the number of potential AMT proteins to at least 12, including members of both the alpha and beta sub-groups. Analysis of the predicted protein sequences for the 12 OsAMT proteins identified many conserved phosphorylation sites in both the alpha and beta group members, which could potentially play a role in controlling the activity of the transporters. Present knowledge of the expression of rice AMT genes is also summarized in detail. Future studies should focus on the structural and functional characteristics of OsAMT proteins to provide insight into the mechanism of ammonium uptake and its regulation in rice. Such research could improve utilization and decrease wastage of N fertilizer in rice cultivation.
文摘In recent years, the improvement of technology and the increase in knowledge have shifted several strongly held paradigms. This is particularly true in gastroenterology, and specifically in the field of the so-called "functional" or "idiopathic" disease, where conditions thought for decades to be based mainly on alterations of visceral perception or aberrant psychosomatic mechanisms have, in fact, be reconducted to an organic basis (or, at the very least, have shown one or more demonstrable abnormalities). This is particularly true, for instance, for irritable bowel syndrome, the prototype entity of "functional" gastrointestinal disorders, where low-grade inflammation of both mucosa and myenteric plexus has been repeatedly demonstrated. Thus, researchers have also investigated other functional/idiopathic gastrointestinal disorders, and found that some organic ground is present, such as abnormal neurotransmission and myenteric plexitis in esophageal achalasia and mucosal immune activation and mild eosinophilia in functional dyspepsia. Here we show evidence, based on our own and other authors' work, that chronic constipation has several abnormalities reconductable to alterations in the enteric nervous system, abnormalities mainly characterized by a constant decrease of enteric glial cells and interstitial cells of Cajal (and, sometimes, of enteric neurons). Thus, we feel that (at least some forms of) chronic constipation should no more be considered as a functional/idiopathic gastrointestinal disorder, but instead as a true enteric neuropathic abnormality.
基金Supported by Mahmoud Reza Pourkarim is supported by a postdoctoral grant from the''Fonds voor Wetenschappelijk Onderzoek Vlaanderen''
文摘The clinical course of infections with the hepatitis B virus (HBV) substantially varies between individuals, as a consequence of a complex interplay between viral, host, environmental and other factors. Due to the high genetic variability of HBV, the virus can be categorized into different HBV genotypes and subgenotypes, which considerably differ with respect to geographical distribution, transmission routes, disease progression, responses to antiviral therapy or vaccination, and clinical outcome measures such as cirrhosis or hepatocellular carcinoma. However, HBV (sub)genotyping has caused some controversies in the past due to misclassifications and incorrect interpretations of different genotyping methods. Thus, an accurate, holistic and dynamic classification system is essential. In this review article, we aimed at highlighting potential pitfalls in genetic and phylogenetic analyses of HBV and suggest novel terms for HBV classification. Analyzing full-length genome sequences when classifying genotypes and subgenotypes is the foremost prerequisite of this classification system. Careful attention must be paid to all aspects of phylogenetic analysis, such as bootstrapping values and meeting the necessary thresholds for (sub)genotyping. Quasi-subgenotype refers to subgenotypes that were incorrectly suggested to be novel. As many of these strains were misclassified due to genetic differences resulting from recombination, we propose the term “recombino-subgenotype”. Moreover, immigration is an important confounding facet of global HBV distribution and substantially changes the geographic pattern of HBV (sub)genotypes. We therefore suggest the term “immigro-subgenotype” to distinguish exotic (sub)genotypes from native ones. We are strongly convinced that applying these two proposed terms in HBV classification will help harmonize this rapidly progressing field and allow for improved prophylaxis, diagnosis and treatment.
文摘Pyricularia oryzae anamorph of Magnaporthe oryzae is one of the most notorious fungal pathogens causing severe economic loss in rice production worldwide. Various methods, viz. cultural, biological and molecular approaches, are utilized to counteract this pathogen. Moreover, some tolerant or resistant rice varieties have been developed with the help of breeding programmes. Isolation and molecular characterization of different blast resistance genes now open the gate for new possibilities to elucidate the actual allelic variants of these genes via various molecular breeding and transgenic approaches. However, the behavioral pattern of this fungus breakups the resistance barriers in the resistant or tolerant rice varieties. This host-pathogen barrier will be possibly countered in future research by comparative genomics data from available genome sequence data of rice and M. oryzae for durable resistance. Present review emphasized fascinating recent updates, new molecular breeding approaches, transgenic and genomics approaches(i.e. mi RNA and genome editing) for the management of blast disease in rice. The updated information will be helpful for the durable, resistance breeding programme in rice against blast pathogen.
基金Supported by Grants of the Deutsche Forschungsgemeinschaft,Sonderforschungsbereich-Transregio 19(project B5)
文摘AIM:To investigate molecular phenotypes of myocardial B19V-infection to determine the role of B19V in myocarditis and dilated cardiomyopathy(DCM).METHODS:Endomyocardial biopsies(EMBs) from 498 B19V-positive patients with myocarditis and DCMwere analyzed using molecular methods and functional experiments.EMBs were obtained from the University Hospitals of Greifswald and Tuebingen and additionally from 36 German cardiology centers.Control tissues were obtained at autopsy from 34 victims of accidents,crime or suicide.Identification of mononuclear cell infiltrates in EMBs was performed using immunohistological staining.Anti-B19V-IgM and anti-B19V-IgG were analyzed by enzyme-linked immunosorbent assay(ELISA).B19V viral loads were determined using in-house quantitative real-time polymerase chain reaction(PCR).For B19V-genotyping a new B19V-genotype-specific restriction fragment length polymorphism(RFLP)-PCR was established.B19V-genotyping was verified by direct DNAsequencing and sequences were aligned using BLAST and BioEdit software.B19V P6-promoter and HHV6-U94-transactivator constructs were generated for cell culture experiments.Transfection experiments were conducted using human endothelial cells 1.Luciferase reporter assays were performed to determine B19Vreplication activity.Statistical analysis and graphical representation were calculated using SPSS and Prism5 software.RESULTS:The prevalence of B19V was significantly more likely to be associated with inflammatory cardiomyopathy(iCMP) compared to uninflamed DCM(59.6% vs 35.3%)(P < 0.0001).The detection of B19V-mRNA replication intermediates proved that replication of B19V was present.RFLP-PCR assays showed that B19V-genotype 1(57.4%) and B19V-genotype 2(36.7%) were the most prevalent viral genotypes.B19V-genotype 2 was observed more frequently in EMBs with iCMP(65.0%) compared to DCM(35%)(P = 0.049).Although there was no significant difference in gender-specific B19V-loads,women were more frequently infected with B19V-genotype 2(44.6%) than men(36.0%)(P = 0.0448).Coinfection with B19V and other cardiotropic viruses was found in 19.2% of tissuesamples and was associated with higher B19V viral load compared to B19V-monoinfected tissue(P = 0.0012).The most frequent coinfecting virus was human herpes virus 6(HHV6,16.5%).B19V-coinfection with HHV6 showed higher B19V-loads compared to B19V-monoinfected EMBs(P = 0.0033),suggesting that HHV6 had transactivated B19V.In vitro experiments confirmed a 2.4-fold increased B19V P6-promoter activity by the HHV6 U94-transactivator.CONCLUSION:The finding of significantly increased B19V loads in patients with histologically proven cardiac inflammation suggests a crucial role of B19V-genotypes and reactivation of B19V-infection by HHV6-coinfection in B19V-associated iCMP.Our findings suggest that B19V-infection of the human heart can be a causative event for the development of an endothelial cell-mediated inflammatory disease and that this is related to both viral load and genotype.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.81903078,82002647,82103623,and 81761168038)the RGC(Grant Nos.26102719 and 16101021)+2 种基金the ITC(Grant Nos.MHP/004/19 and ITCPD/17-9)the Beijing Nova Program(Grant No.Z201100006820118)MOST(Grant No.2019YFE0109400).
文摘Objective:We aimed to summarize the clinicopathological characteristics and prognostic features of various molecular subtypes of diffuse gliomas(DGs)in the Chinese population.Methods:In total,1,418 patients diagnosed with DG between 2011 and 2017 were classified into 5 molecular subtypes according to the 2016 WHO classification of central nervous system tumors.The IDH mutation status was determined by immunohistochemistry and/or DNA sequencing,and 1p/19q codeletion was detected with fluorescence in situ hybridization.The median clinical follow-up time was 1,076 days.T-tests and chi-square tests were used to compare clinicopathological characteristics.Kaplan‒Meier and Cox regression methods were used to evaluate prognostic factors.Results:Our cohort included 15.5%lower-grade gliomas,IDH-mutant and 1p/19q-codeleted(LGG-IDHm-1p/19q);18.1%lowergrade gliomas,IDH-mutant(LGG-IDHm);13.1%lower-grade gliomas,IDH-wildtype(LGG-IDHwt);36.1%glioblastoma,IDHwildtype(GBM-IDHwt);and 17.2%glioblastoma,IDH-mutant(GBM-IDHm).Approximately 63.3%of the enrolled primary gliomas,and the median overall survival times for LGG-IDHm,LGG-IDHwt,GBM-IDHwt,and GBM-IDHm subtypes were 75.97,34.47,11.57,and 15.17 months,respectively.The 5-year survival rate of LGG-IDHm-1p/19q was 76.54%.We observed a significant association between high resection rate and favorable survival outcomes across all subtypes of primary tumors.We also observed a significant role of chemotherapy in prolonging overall survival for GBM-IDHwt and GBM-IDHm,and in prolonging post-relapse survival for the 2 recurrent GBM subtypes.Conclusions:By controlling for molecular subtypes,we found that resection rate and chemotherapy were 2 prognostic factors associated with survival outcomes in a Chinese cohort with DG.
基金supported by the China Natural Science Foundation grants (Nos. 30670736 and 30972655)the National Basic Research Program of China (973 Program) (No. 2007CB512002).
文摘Osteogenesis imperfecta（OI,also known as brittle bone disease）is caused mostly by mutations in two type I collagen genes,COL1A1 and COLIA2 encoding the pro-α1（I）and pro-α2（I）chains of type I collagen,respectively.Two Chinese families with autosomal dominant OI were identified and characterized.Linkage analysis revealed linkage of both families to COL1A2 on chromosome 7q21.3-q22.1.Mutational analysis was carried out using direct DNA sequence analysis.Two novel missense mutations,c.3350AG and c.3305GC,were identified in exon 49 of COL1A2 in the two families,respectively.The c.3305GC mutation resulted in substitution of a glycine residue（G）by an alanine residue（A）at codon 1102（p.G1102A）,which was found to be mutated into serine（S）,argine（R）,aspartic acid（D）,or valine（V）in other families.The c.3350AG variant may be a de novo mutation resulting in p.Y1117C.Both mutations co-segregated with OI in respective families,and were not found in 100 normal controls.The G1102 and Y1117 residues were evolutionarily highly conserved from zebrafish to humans.Mutational analysis did not identify any mutation in the COX-2 gene（a modifier gene of OI）.This study identifies two novel mutations p.G1102A and p.Y1117C that cause OI,significantly expands the spectrum of COL1A2 mutations causing OI,and has a significant implication in prenatal diagnosis of OI.
文摘Positron emission tomography measures the activity of radioactively labeled compounds which distribute and accumulate in central nervous system regions in proportion to their metabolic rate or blood flow. Specific circuits such as the dopaminergic nigrostriatal projection can be studied with ligands that bind to the pre-synaptic dopamine transporter or post-synaptic dopamine receptors (D1 and D2). Single photon emission computerized tomography (SPECT) measures the activity of similar tracers labeled with heavy radioactive species such as technetium and iodine. In essential tremor, there is cerebellar hypermetabolism and abnormal GABAergic function in premotor cortices, dentate nuclei and ventral thalami, without significant abnormalities in dopaminergic transmission. In Huntington’s disease, there is hypometabolism in the striatum, frontal and temporal cortices. Disease progression is accompanied by reduction in striatal D1 and D2 binding that correlates with trinucleotide repeat length, disease duration and severity. In dystonia, there is hypermetabolism in the basal ganglia, supplementary motor areas and cerebellum at rest. Thalamic and cerebellar hypermetabolism is seen during dystonic movements, which can be modulated by globus pallidus deep brain stimulation (DBS). Additionally, GABA-A receptor activity is reduced in motor, premotor and somatosensory cortices. In Tourette’s syndrome, there is hypermetabolism in premotor and sensorimotor cortices, as well as hypometabolism in the striatum, thalamus and limbic regions at rest. During tics, multiple areas related to cognitive, sensory and motor functions become hypermetabolic. Also, there is abnormal serotoninergic transmission in prefrontal cortices and bilateral thalami, as well as hyperactivity in the striatal dopaminergic system which can be modulated with thalamic DBS. In Parkinson’s disease (PD), there is asymmetric progressive decline in striatal dopaminergic tracer accumulation, which follows a caudal-to-rostral direction. Uptake declines prior to symptom presentation and progresses from contralateral to the most symptomatic side to bilateral, correlating with symptom severity. In progressive supranuclear palsy (PSP) and multiple system atrophy (MSA), striatal activity is symmetrically and diffusely decreased. The caudal-to-rostral pattern is lost in PSP, but could be present in MSA. In corticobasal degeneration (CBD), there is asymmetric, diffuse reduction of striatal activity, contralateral to the most symptomatic side. Additionally, there is hypometabolism in contralateral parieto-occipital and frontal cortices in PD; bilateral putamen and cerebellum in MSA; caudate, thalamus, midbrain, mesial frontal and prefrontal cortices in PSP; and contralateral cortices in CBD. Finally, cardiac sympathetic SPECT signal is decreased in PD. The capacity of molecular imaging to provide in vivo time courses of gene expression, protein synthesis, receptor and transporter binding, could facilitate the development and evaluation of novel medical, surgical and genetic therapies in movement disorders.
基金supported by National Natural Science Foundation of China(Grant No.81202795)China Postdoctoral Science Foundation(Grant No.2015M571271)
文摘Precision medicine and personalized therapy are receiving increased attention, and molecular-subtype classification has become crucial in planning therapeutic schedules in clinical practice for patients with breast cancer. Human epidermal growth factor receptor 2(HER2) is associated with high-grade breast tumors, high rates of lymph-node involvement, high risk of recurrence, and high resistance to general chemotherapy. Analysis of HER2 expression is highly important for doctors to identify patients who can benefit from trastuzumab therapy and monitor the response and efficacy of treatment. In recent years, significant efforts have been devoted to achieving specific and noninvasive HER2-positive breast cancer imaging in vivo. In this work, we reviewed existing literature on HER2 imaging in the past decade and summarized the studies from different points of view, such as imaging modalities and HER2-specific probes. We aimed to improve the understanding on the translational process in molecular imaging for HER2 breast cancer.
基金Supported by The Japan Society for the Promotion of Science(JSPS) through KAKENHI grants 25670774 and 15K11004,awarded to Funato N
文摘Cleft palate, including complete or incomplete cleft palates, soft palate clefts, and submucosal cleft palates, is the most frequent congenital craniofacial anomaly in humans. Multifactorial conditions, including genetic and environmental factors, induce the formation of cleft palates. The process of palatogenesis is temporospatially regulated by transcription factors, growth factors, extracellular matrix proteins, and membranous molecules; a single ablation of these molecules can result in a cleft palate in vivo. Studies on knockout mice were reviewed in order to identify genetic errors that lead to cleft palates. In this review, we systematically describe these mutant mice and discuss the molecular mechanisms of palatogenesis.
基金supported by the National Natural Science Foundation of China(Nos.U1706212 and 81671828)
文摘Uniform molecular weight(Mw)chitosan(CS)is highly demanded in medical biomaterial industry.This present article described heterogeneous degradation of CS in aqueous HCl/ethanol solution,in which progress uniform Mw CS was successfully prepared.The Mw distribution of CS was measured by gel permeation chromatography(GPC)analysis.Moreover,the structure and properties of degraded CS were characterized by Fourier transform infrared spectroscopy(FT-IR),nuclear magnetic resonance spectroscopy(^1H NMR),X-ray diffraction(XRD)and thermogravimetric(TG)analysis.In addition,the biocompatibility of degraded CS was also assessed by hemolysis rate(HR)measurement.The Mw of CS dramatically decreased from 246 KDa to 76 k Da at the initial 30 min,and stabilized at 18 kDa after 24 h.GPC analysis results showed that the degraded CS molecular become homogenization.FT-IR and 1 H NMR analysis confirmed the basic structure of CS molecular backbone was not destroyed during this progress.Besides,the water solubility of CS was not significantly influenced by this reaction.Moreover,the XRD analysis revealed that crystallinity of degraded CS increased from 70.32% to 99.25%with time.The TG analysis showed improved thermal stability of degraded CS.HR measurement demonstrated the degraded CS possessed excellent biocompatibility.This simple and efficient heterogeneous degradation would open up a new route to produce uniform Mw CS.
文摘Wiedemann-Steiner syndrome(OMIM#605130)is a rare congenital malformation syndrome characterized by hypertrichosis cubiti associated with short stature;consistent facial features,including long eyelashes,thick or arched eyebrows with a lateral flare,wide nasal bridge,and downslanting and vertically narrow palpebral fissures;mild to moderate intellectual disability;behavioral difficulties;and hypertrichosis on the back.It is caused by heterozygous pathogenic variants in KMT2A.This gene has an established role in histone methylation,which explains the overlap of Wiedemann-Steiner syndrome with other chromatinopathies,a heterogeneous group of syndromic conditions that share a common trigger:The disruption of one of the genes involved in chromatin modification,leading to dysfunction of the epigenetic machinery.
文摘The molecular chaperone HSP60 is a chaperonin homolog of GroEL. We had previously shown that the immunosuppressant mizoribine is bound directly to HSP60 and inhibited its chaperone activity. However, the inhibitory mechanisms of HSP60 by mizoribine have not yet been fully understood. In the present study, we investigated the influence of mizoribine on a folding cycle of HSP60 and co-chaperone HSP10. Our results showed that mizoribine inhibited the folding cycle of HSP60/HSP10. The ATPase activity of HSP60/HSP10 was decreased in the presence of mizoribine and the dissociation of HSP10 from HSP-60 was also decreased by mizoribine. The same functions of GroEL and/or GroES were slightly affected by mizoribine. Based on our findings, we discuss the inhibitory mechanisms of HSP60 by mizoribine.
文摘The unique physicochemical properties inherent to nanoscale materials have unveiled numerous potential applications,spanning beyond the pharmaceutical and medical sectors into various consumer industries like food and cosmetics.Consequently,humans encounter nanomaterials through diverse exposure routes,giving rise to potential health considerations.Noteworthy among these materials are silica and specific metallic nanoparticles,extensively utilized in consumer products,which have garnered substantial attention due to their propensity to accumulate and induce adverse effects in the liver.This review paper aims to provide an exhaustive examination of the molecular mechanisms underpinning nanomaterial-induced hepatotoxicity,drawing insights from both in vitro and in vivo studies.Primarily,the most frequently observed manifestations of toxicity following the exposure of cells or animal models to various nanomaterials involve the initiation of oxidative stress and inflammation.Additionally,we delve into the existing in vitro models employed for evaluating the hepatotoxic effects of nanomaterials,emphasizing the persistent endeavors to advance and bolster the reliability of these models for nanotoxicology research.
