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1.
Hum Brain Mapp ; 45(1): e26529, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37991144

ABSTRACT

Mild cognitive impairment (MCI) is a critical prodromal stage of Alzheimer's disease (AD), and the mechanism underlying the conversion is not fully explored. Construction and inter-cohort validation of imaging biomarkers for predicting MCI conversion is of great challenge at present, due to lack of longitudinal cohorts and poor reproducibility of various study-specific imaging indices. We proposed a novel framework for inter-cohort MCI conversion prediction, involving comparison of structural, static, and dynamic functional brain features from structural magnetic resonance imaging (sMRI) and resting-state functional MRI (fMRI) between MCI converters (MCI_C) and non-converters (MCI_NC), and support vector machine for construction of prediction models. A total of 218 MCI patients with 3-year follow-up outcome were selected from two independent cohorts: Shanghai Memory Study cohort for internal cross-validation, and Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort for external validation. In comparison with MCI_NC, MCI_C were mainly characterized by atrophy, regional hyperactivity and inter-network hypo-connectivity, and dynamic alterations characterized by regional and connectional instability, involving medial temporal lobe (MTL), posterior parietal cortex (PPC), and occipital cortex. All imaging-based prediction models achieved an area under the curve (AUC) > 0.7 in both cohorts, with the multi-modality MRI models as the best with excellent performances of AUC > 0.85. Notably, the combination of static and dynamic fMRI resulted in overall better performance as relative to static or dynamic fMRI solely, supporting the contribution of dynamic features. This inter-cohort validation study provides a new insight into the mechanisms of MCI conversion involving brain dynamics, and paves a way for clinical use of structural and functional MRI biomarkers in future.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Humans , Alzheimer Disease/diagnostic imaging , Alzheimer Disease/pathology , Reproducibility of Results , China , Magnetic Resonance Imaging/methods , Neuroimaging/methods , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/pathology , Brain/diagnostic imaging , Brain/pathology , Biomarkers
2.
Alzheimers Dement ; 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38837321

ABSTRACT

INTRODUCTION: The association of testosterone and cognitive decline is inconclusive, and its joint effect with neurofilaments light chain (NfL) remains largely unknown. METHODS: A total of 581 non-demented older men in the Shanghai Aging Study were included. Blood total testosterone (TT), free testosterone (FT), and NfL were measured at baseline. The relationships between TT, FT, TT/FT-NfL, and cognitive decline were explored by Cox regression models. RESULTS: During a median follow-up of 6.7 years, there was an inverse association between TT/FT and cognitive decline (TT, trend p = .004, Q1 vs Q4, hazard ratio [HR] = 4.39, 95% confidence interval [CI] = 1.60 to 12.04; FT, trend p = .002, Q1 vs Q4, HR = 5.29, 95% CI = 1.50 to 16.89). Compared to participants with high TT/FT-low NfL, those with low TT/FT-high NfL had significantly higher risks of cognitive decline (TT, HR = 5.10, 95% CI = 1.11 to 23.40; FT, HR = 6.14, 95% CI = 1.34 to 28.06). DISCUSSION: Our findings suggest that the combination of testosterone and neurodegenerative markers may provide reliable predictive insights into future cognitive decline. HIGHLIGHTS: Testosterone is inversely associated with cognitive decline in older men. There is a joint effect of testosterone and NfL on cognitive decline. Sex hormone and neurodegeneration may synergistically contribute to cognitive deterioration.

3.
Alzheimers Dement ; 20(4): 2516-2525, 2024 04.
Article in English | MEDLINE | ID: mdl-38329281

ABSTRACT

INTRODUCTION: The objective of this study is to investigate the incremental value of amyloid positron emission tomography (Aß-PET) in a tertiary memory clinic setting in China. METHODS: A total of 1073 patients were offered Aß-PET using 18F-florbetapir. The neurologists determined a suspected etiology (Alzheimer's disease [AD] or non-AD) with a percentage estimate of their confidence and medication prescription both before and after receiving the Aß-PET results. RESULTS: After disclosure of the Aß-PET results, etiological diagnoses changed in 19.3% of patients, and diagnostic confidence increased from 69.3% to 85.6%. Amyloid PET results led to a change of treatment plan in 36.5% of patients. Compared to the late-onset group, the early-onset group had a more frequent change in diagnoses and a higher increase in diagnostic confidence. DISCUSSION: Aß-PET has significant impacts on the changes of diagnoses and management in Chinese population. Early-onset cases are more likely to benefit from Aß-PET than late-onset cases. HIGHLIGHTS: Amyloid PET contributes to diagnostic changes and its confidence in Chinese patients. Amyloid PET leads to a change of treatment plans in Chinese patients. Early-onset cases are more likely to benefit from amyloid PET than late-onset cases.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Humans , Amyloid , Alzheimer Disease/diagnostic imaging , Positron-Emission Tomography/methods , Amyloidogenic Proteins , Aniline Compounds , China , Amyloid beta-Peptides , Cognitive Dysfunction/diagnosis
4.
Clin Chem ; 68(12): 1552-1563, 2022 12 06.
Article in English | MEDLINE | ID: mdl-36208187

ABSTRACT

BACKGROUND: Previous studies reported the value of blood-based biomarkers in predicting Alzheimer disease (AD) progression among individuals with different disease stages. However, evidence regarding the value of these markers in those with amnestic mild cognitive impairment (aMCI) is insufficient. METHODS: A cohort with 251 aMCI individuals were followed for up to 8 years. Baseline blood biomarkers were measured on a single-molecule array platform. Multipoint clinical diagnosis and domain-specific cognitive functions were assessed to investigate the longitudinal relationship between blood biomarkers and clinical AD progression. RESULTS: Individuals with low Aß42/Aß40 and high p-tau181 at baseline demonstrated the highest AD risk (hazard ratio = 4.83, 95% CI 2.37-9.86), and the most dramatic decline across cognitive domains. Aß42/Aß40 and p-tau181, combined with basic characteristics performed the best in predicting AD conversion (AUC = 0.825, 95% CI 0.771-0.878). CONCLUSIONS: Combining Aß42/Aß40 and p-tau181 may be a feasible indicator for AD progression in clinical practice, and a potential composite marker in clinical trials.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Humans , Alzheimer Disease/diagnosis , Amyloid beta-Peptides , Cognitive Dysfunction/diagnosis , Peptide Fragments , Biomarkers , tau Proteins
5.
Diabetes Metab Res Rev ; 38(3): e3501, 2022 03.
Article in English | MEDLINE | ID: mdl-34614535

ABSTRACT

AIMS AND OBJECTIVES: Fulminant type 1 diabetes (FT1D) could present diabetes ketoacidosis (DKA) at early onset. It is crucial to identify FT1D from DKA manifestations in time at clinical practice. This study was aimed at investigating whether the fulminant index (FI), encompassing plasma glucose (PG) to glycated haemoglobin (HbA1c) ratio (PG/HbA1c), serum potassium ion (K+ ) to HbA1c ratio (K+ /HbA1c) and serum sodium ion (Na+ ) multiplied by HbA1c (Na+ *HbA1c), is a feasible indicator for early FT1D diagnosis. MATERIALS AND METHODS: A total of 78 subjects were enroled, including 40 FT1D patients and 38 non-FT1D patients with DKA. We utilised receiver operating characteristic (ROC) curve analysis to determine the FI cut-off values between FT1D and non-FT1D groups and examined efficacies of FI based on statistics. RESULTS: ROC curve analyses showed that the maximum Youden's index for PG/HbA1c bonding to a cut-off value of 4.389, with the sensitivity of 75.0% and specificity of 81.6% in identifying FT1D from DKA. And optimal K+ /HbA1c cut-off value was 0.728 with a sensitivity of 90.0% and specificity of 84.2%. For Na+ *HbA1c, the best cut-off value was 923.65, and its sensitivity and specificity were 85% and 73.7%, respectively. CONCLUSIONS: These results suggested FI could work as a valid and convenient indicator for differentiating FT1D from initial DKA patients. FI (K+ /HbA1c) presented the best efficacy as an independent index.


Subject(s)
Diabetes Mellitus, Type 1 , Diabetic Ketoacidosis , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/diagnosis , Diabetic Ketoacidosis/diagnosis , Diabetic Ketoacidosis/etiology , Glycated Hemoglobin/analysis , Humans , ROC Curve
6.
Neoplasma ; 68(4): 875-881, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33998235

ABSTRACT

The relationship between 18F-FDG uptake and HER2 expression in colorectal cancer has not been investigated yet. This study aimed to investigate the predictive efficiency of preoperative 18F-FDG PET/CT for HER2 expression and prognosis in colorectal cancer. We retrospectively analyzed 131 colorectal cancer patients who underwent 18F-FDG PET/CT scans in our center before surgery. HER2 positivity was defined as a score of 2+ or 3+, and HER2 negativity was defined as a score of 0 or 1+ in immunohistochemistry of HER2 expression. The relationships between 18F-FDG PET/CT metabolic parameters and HER2 expression and the prognosis of colorectal patients were systematically studied. From 131 colorectal cancer patients, there were 27 (20.6%) HER2-positive patients. SUVmax of the primary tumor (mean ± SD) in the HER2-positive and the HER2-negative group was 18.238±8.912 and 14.455±6.531, respectively. SUVmax in the HER2-positive group was higher than in the negative group (p=0.034). When the cutoff was based on 5 cm, tumor size demonstrated significant positive correlations with SUVmax (p=0.012) and HER2 expression (p=0.014). Multivariate analysis showed that both SUVmax and tumor size had a significant correlation with HER2 expression (p=0.049 vs. p=0.043, respectively). There was no statistical difference in PFS between the HER2-positive and the HER2-negative group (p=0.28). 18F-FDG metabolic parameters had a significant correlation with HER2 expression in colorectal cancer. SUVmax combined with primary tumor size were better for predicting the HER2 status of colorectal cancer. 18F-FDG metabolic parameters had a significant correlation with HER2 expression in colorectal cancer. SUVmax combined with primary tumor size were better for predicting the HER2 status of colorectal cancer.


Subject(s)
Colorectal Neoplasms , Fluorodeoxyglucose F18 , Colorectal Neoplasms/diagnostic imaging , Humans , Positron Emission Tomography Computed Tomography , Radiopharmaceuticals , Receptor, ErbB-2 , Retrospective Studies
7.
Urol Int ; 105(5-6): 370-379, 2021.
Article in English | MEDLINE | ID: mdl-33302278

ABSTRACT

BACKGROUND: It has been reported that compared with no local therapy (NLT), patients treated with local therapy (LT) using radiotherapy (RT) possess higher survival rate in metastatic prostate cancer (mPCa). The aim of this meta-analysis was to evaluate the impact of RT on prognosis in patients with mPCa. METHODS: We retrieved the literature in PubMed, Embase, and Cochrane Library databases until June 2019 using structured search terms. Several studies were included, which evaluated patients with mPCa who received RT versus NLT. RESULTS: A total of 14,542 patients were analyzed in 7 included papers (2 randomized controlled trials [RCTs] and 5 cohort retrospective studies [CRS]), and 2,232 mPCa patients were treated with RT and 12,310 with NLT. The data of RCTs and CRS were analyzed separately. In RCTs, RT was associated with no significant difference in overall survival (OS) (pooled hazard ratio [HR] = 0.96; 95% confidence interval [CI]: 0.85-1.09; p = 0.55; I2 = 42%) relative to NLT, while survival benefit was observed in the low-metastatic burden group (pooled HR = 0.68; 95% CI: 0.54-0.86; p = 0.001; I2 = 0%), and no survival benefit was observed in the high-metastatic burden group (pooled HR = 1.07; 95% CI: 0.92-1.24; p = 0.39; I2 = 0%). In CRS, RT results in lower cancer-specific mortality (CSM) (pooled HR = 0.49; 95% CI: 0.34-0.75; p < 0.00001; I2 = 0%) and higher OS (pooled HR = 0.61; 95% CI: 0.55-0.68; p < 0.00001; I2 = 0%) relative to NLT. Subsequent analysis demonstrated that high level of M-stage or N-stage was associated with increased CSM (pooled HR = 2.08; 95% CI: 1.69-2.55; p < 0.00001; I2 = 0% and pooled HR = 1.16; 95% CI: 1.03-1.30; p < 0.00001; I2 = 0%; respectively). CONCLUSIONS: Our observations in aggregate indicated that RT at least does not appear to be harmful and may be beneficial for low-metastatic burden patients and better condition patients. More prospective and randomized studies evaluating RT for mPCa are warranted.


Subject(s)
Prostatic Neoplasms/mortality , Prostatic Neoplasms/radiotherapy , Humans , Male , Neoplasm Metastasis , Prognosis , Prostatic Neoplasms/pathology , Survival Rate
8.
Diabetes Metab Res Rev ; 36(6): e3317, 2020 09.
Article in English | MEDLINE | ID: mdl-32223049

ABSTRACT

Fulminant type 1 diabetes (FT1D) is a subset of type 1 diabetes characterized by extremely rapid pancreatic ß-cell destruction with aggressive progression of hyperglycaemia and ketoacidosis. It was initially classified as idiopathic type 1 diabetes due to the absence of autoimmune markers. However, subsequent studies provide evidences supporting the involvement of autoimmunity in rapid ß-cell loss in FT1D pathogenesis, which are crucial for FT1D being an autoimmune disease. This article highlights the role of immunological aspects in FT1D according to the autoimmune-associated genetic background, viral infection, innate immunity, adaptive immunity, and pancreas histology.


Subject(s)
Autoimmunity/immunology , Diabetes Mellitus, Type 1/complications , Diabetic Ketoacidosis/etiology , Hyperglycemia/etiology , Insulin-Secreting Cells/pathology , Diabetic Ketoacidosis/pathology , Disease Progression , Humans , Hyperglycemia/pathology , Prognosis
9.
Anal Bioanal Chem ; 406(21): 5147-55, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24633508

ABSTRACT

Ricin is a toxic protein derived from castor beans and composed of a cytotoxic A chain and a galactose-binding B chain linked by a disulfide bond, which can inhibit protein synthesis and cause cell death. Owing to its high toxicity, ease of preparation, and lack of medical countermeasures, ricin has been listed as both chemical and biological warfare agents. For homeland security or public safety, the unambiguous, sensitive, and rapid methods for identification and quantification of ricin in complicated matrices are of urgent need. Mass spectrometric analysis, which provides specific and sensitive characterization of protein, can be applied to confirm and quantify ricin. Here, we report a liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) method in which ricin was extracted and enriched from serum by immunocapture using anti-ricin monoclonal antibody 3D74 linked to magnetic beads, then digested by trypsin, and analyzed by LC-ESI-MS/MS. Among 19 distinct peptides observed in LC-quadrupole/time of flight-MS (LC-QTOF-MS), two specific and sensitive peptides, T7A ((49)VGLPINQR(56)) and T14B ((188)DNCLTSDSNIR(198)), were chosen, and a highly sensitive determination of ricin was established in LC-triple quadrupole-MS (LC-QqQ-MS) operating in multiple reaction monitoring mode. These specific peptides can definitely distinguish ricin from the homologous protein Ricinus communis agglutinin (RCA120), even though the amino acid sequence homology of the A-chain of ricin and RCA120 is up to ca. 93% and that of B-chain is ca. 85%. Furthermore, peptide T7A was preferred in the quantification of ricin because its sensitivity was at least one order of magnitude higher than that of the peptide T14B. Combined with immunocapture enrichment, this method provided a limit of detection of ca. 2.5 ng/mL and the limit of quantification was ca. 5 ng/mL of ricin in serum, respectively. Both precision and accuracy of this method were determined and the RSD was less than 15%. This established method was then applied to measure ricin in serum samples collected from rats exposed to ricin at the dosage of 50 µg/kg in an intravenous injection manner. The results showed that ca. 10 ng/mL of the residual ricin in poisoned rats serum could be detected even at 12 h after exposure.


Subject(s)
Antibodies, Monoclonal/chemistry , Biological Warfare Agents , Chemical Warfare Agents/isolation & purification , Peptide Fragments/analysis , Ricin/blood , Animals , Chromatography, Liquid , Immunoprecipitation , Limit of Detection , Magnets , Male , Plant Lectins/analysis , Rats , Rats, Sprague-Dawley , Spectrometry, Mass, Electrospray Ionization , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Trypsin/chemistry
10.
Zhongguo Zhong Yao Za Zhi ; 39(12): 2184-8, 2014 Jun.
Article in Zh | MEDLINE | ID: mdl-25244741

ABSTRACT

In order to identify Cimicifugae Rhizoma from its adulterants and to ensure its safe use, the internal transcribed spacer 2 (ITS2) sequence of Cimicifugae Rhizoma and its adulterants were amplified and bidirectionally sequenced by DNA barcoding technology. Sequence assembly and consensus sequence generation were performed by the CodonCode Aligner V3.7.1. The genetic distances were computed by MEGA 5.0. Identification analyses were performed using neighbor-joining (NJ) methods. The length of ITS2 sequence of the three origin plants of Cimicifugae Rhizoma include Cimicifuga heracleifolia, C. foetida, C. dahurica was 217, 219 and 219 bp, respectively. Their intraspecific genetic distance was much lower than the interspecific genetic distance with their closely related species. The NJ tree of ITS2 indicated that the three origin plants of Cimicifugae Rhizoma formed a monophyletic clade, Cimicifugae Rhizoma and its adulterants could be distinguished clearly. The authors proposed that ITS2 sequence was suitable for the authentication of Cimicifugae Rhizoma and its adulterants.


Subject(s)
Cimicifuga/classification , DNA Barcoding, Taxonomic/methods , DNA, Plant/genetics , DNA, Ribosomal Spacer/genetics , Drugs, Chinese Herbal/classification , Base Sequence , China , Cimicifuga/genetics , Drug Contamination/prevention & control , Drugs, Chinese Herbal/chemistry , Molecular Sequence Data , Phylogeny , Quality Control , Rhizome/classification , Rhizome/genetics
11.
Zhongguo Zhong Yao Za Zhi ; 39(12): 2189-93, 2014 Jun.
Article in Zh | MEDLINE | ID: mdl-25244742

ABSTRACT

DNA barcoding method was conducted for the authentication of pollen materials due to difficulty of discriminating pollen materials bearing morphological similarity. In this study, a specific focus was to identify cattail pollen (Puhuang) and pine pollen (Songhuafen) samples from their adulterants which are frequently mixed-together. Regions of the internal transcribed spacer (ITS2) from 60 samples were sequenced, and new primers for cattail pollen were designed according to the sequence information. The results from the NJ trees showed that the species of pine pollen, Puhuang and their adulterants can be classified as obvious monophyly. Therefore, we propose to adapt DNA barcoding methodology to accurately distinguish cattail pollen, pine pollen and their adulterant materials. It is a great help for drug regulatory agency to supervise the quality of medicinal materials.


Subject(s)
DNA Barcoding, Taxonomic/methods , DNA, Plant/genetics , DNA, Ribosomal Spacer/genetics , Drugs, Chinese Herbal/classification , Pinus/classification , Typhaceae/classification , China , Drug Contamination/prevention & control , Drugs, Chinese Herbal/chemistry , Molecular Sequence Data , Phylogeny , Pinus/genetics , Pollen/classification , Pollen/genetics , Quality Control , Typhaceae/genetics
12.
Zhongguo Zhong Yao Za Zhi ; 39(12): 2222-6, 2014 Jun.
Article in Zh | MEDLINE | ID: mdl-25244749

ABSTRACT

In this study, the psbA-trnH sequence as DNA barcode was used to evaluate the accuracy and stability for identification pteridophyte medicinal material Pyrrosiae Foliumas from adulterants. Genomic DNA from 106 samples were extracted successfully. The Kimura 2-Parameter (K2P) distances and ML tree were calculated using software MEGA 6.0. The intra-specific genetic distances of 3 original plants were lower than inter-specific genetic distances of adulterants. The ML tree indicated that Pyrrosiae Folium can be distinguished from its adulterants obviously. Therefore, the psbA-trnH sequence as a barcode of the pteridophyte, can accurately and stably distinguish Pyrrosiae Folium from its adulterants.


Subject(s)
DNA Barcoding, Taxonomic/methods , Drugs, Chinese Herbal/classification , Ferns/classification , Ferns/genetics , Plant Proteins/genetics , Base Sequence , DNA, Ribosomal Spacer/genetics , Drug Contamination/prevention & control , Drugs, Chinese Herbal/chemistry , Molecular Sequence Data , Phylogeny , Quality Control
13.
Zhongguo Zhong Yao Za Zhi ; 39(12): 2227-32, 2014 Jun.
Article in Zh | MEDLINE | ID: mdl-25244750

ABSTRACT

In order to evaluate the efficiency of ITS2 and psbA-trnH sequences used as DNA barcodes to distinguish Plantaginis Semen from its adulterants, we collected 71 samples of Plantaginis Semen and its adulterants. The ITS2 and psbA-trnH sequences were aligned through Clustal W, and the genetic distances were calculated by kimura 2-parameter (K2P) model and the Neighbor-Joining (NJ) phylogenetic trees were constructed using MEGA 5.1. The results indicated that the ITS2 sequence lengths of Plantago asiatica and P. depressa were 199 bp and 200 bp, respectively; the maximum intra-specific K2P distance were lower than the minimum inter-specific K2P distance; the NJ tree based on ITS2 sequence indicated that Plantaginis Semen and its adulterants could be distinguished clearly. The sequence lengths of psbA-trnH of both P. asiatica and P. depressa were 340 bp; the maximum intra-specific K2P distances were lower than the minimum inter-specific K2P distance; the NJ tree based on psbA-trnH sequence showed that Plantaginis Semen can be distinguished clearly from its adulterants except for P. major. Therefore, ITS2 sequences can be used as an ideal DNA barcode to distinguish Plantaginis Semen from its adulterants.


Subject(s)
DNA Barcoding, Taxonomic/methods , Drugs, Chinese Herbal/classification , Plant Proteins/genetics , Plantago/classification , Plantago/genetics , Base Sequence , DNA, Plant/genetics , DNA, Ribosomal Spacer/genetics , Drug Contamination/prevention & control , Drugs, Chinese Herbal/chemistry , Molecular Sequence Data , Phylogeny , Quality Control , Seeds/classification , Seeds/genetics
14.
Front Aging Neurosci ; 16: 1411031, 2024.
Article in English | MEDLINE | ID: mdl-38915349

ABSTRACT

Background: Olfactory dysfunction was associated with poorer cognition. However, the association between transient receptor potential cation channel subfamily A member 1 (TRPA1) and cognitive function have not been studied. This study aimed to evaluate the mediation effect of TRPA1 on the association between olfactory and cognitive function among Chinese older adults. Methods: We recruited 121 participants with cognitive impairment (CI) and 135 participants with normal cognition (NC) from a memory clinic and the "Shanghai Aging Study." Olfactory identification of each participant was measured by the Sniffin' Sticks Screening Test 12 (SSST-12). Serum TRPA1 were quantified using the Enzyme-Linked Immunosorbent Assay. The mediation effects of TRPA1 on the association between olfactory function and cognitive function were explored using mediation analysis. Results: The CI group had a significantly higher proportion of the high level of serum TRPA1 (58.7%) than the NC group (42.2%) (p = 0.0086). After adjusted for gender, age, and years of education, mediation analysis verified that TRPA1 partially mediated the association between SSST-12 and Mini Mental State Examination (MMSE). It also verified that TRPA1 partially mediated the association between the identification of peppermint and MMSE. Conclusion: Our study emphasizes the mediation role of TRPA1 in the relationship between olfactory and cognitive function among older adults. Further research is necessary to explore the mechanism of TRPA1 on the relationship between olfactory and cognitive decline.

15.
Adv Healthc Mater ; 13(5): e2302302, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38078359

ABSTRACT

Blood-brain-barrier (BBB) serves as a fatal guard of the central nervous system as well as a formidable obstacle for the treatment of brain diseases such as brain tumors. Cell membrane-derived nanomedicines are promising drug carriers to achieve BBB-penetrating and brain lesion targeting. However, the challenge of precise size control of such nanomedicines has severely limited their therapeutic effect and clinical application in brain diseases. To address this problem, this work develops a microfluidic mixing platform that enables the fabrication of cell membrane-derived nanovesicles with precise controllability and tunability in particle size and component. Sub-100 nm macrophage plasma membrane-derived vesicles as small as 51 nm (nanoscale macrophage vesicles, NMVs), with a narrow size distribution (polydispersity index, PDI: 0.27) and a high drug loading rate (up to 89% for indocyanine green-loaded NMVs, NMVs@ICG (ICG is indocyanine green)), are achieved through a one-step process. Compared to beyond-100 nm macrophage cell membrane vesicles (general macrophage vesicles, GMVs) prepared via the traditional methods, the new NMVs exhibits rapid (within 1 h post-injection) and enhanced orthotopic glioma targeting (up to 78% enhancement), with no extra surface modification. This work demonstrates the great potential of such real-nanoscale cell membrane-derived nanomedicines in targeted brain tumor theranostics.


Subject(s)
Brain Neoplasms , Nanoparticles , Humans , Microfluidics , Indocyanine Green/therapeutic use , Biomimetics , Cell Line, Tumor , Brain Neoplasms/drug therapy , Brain Neoplasms/pathology
16.
RSC Adv ; 14(11): 7924-7931, 2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38449818

ABSTRACT

Designing and synthesizing well-defined crystalline catalysts for the photocatalytic oxidative coupling of amines to imines remains a great challenge. In this work, a crystalline dumbbell-shaped titanium oxo cluster, [Ti10O6(Thdc)(Dmg)2(iPrO)22] (Ti10, Thdc = 2,5-thiophenedicarboxylic acid, Dmg = dimethylglyoxime, iPrOH = isopropanol), was constructed through a facile one-pot solvothermal strategy and treated as a catalyst for the photocatalytic oxidative coupling of amines. In this structure, Thdc serves as the horizontal bar, while the {Ti5Dmg} layers on each side act as the weight plates. The molecular structure, light absorption, and photoelectrochemical properties of Ti10 were systematically investigated. Remarkably, the inclusion of the Thdc ligand, with the assistance of the Dmg ligand, broadens the light absorption spectrum of Ti10, extending it into the visible range. Furthermore, the effective enhancement of charge transfer within the Ti10 was achieved with the successful incorporation of the Thdc ligand, as opposed to PTC-211, where terephthalic acid replaces the Thdc ligand, while maintaining consistency in other aspects of Ti10. Building on this foundation, Ti10 was employed as a heterogeneous molecular photocatalyst for the catalytic oxidative coupling reaction of benzylamine (BA), demonstrating very high conversion activity and selectivity. Our study illustrates that the inclusion of ligands derived from Thdc enhances the efficiency of charge transfer in functionalized photocatalysts, significantly influencing the performance of photocatalytic organic conversion.

17.
Alzheimers Res Ther ; 16(1): 32, 2024 02 12.
Article in English | MEDLINE | ID: mdl-38347655

ABSTRACT

BACKGROUND: The blood-based biomarkers are approaching the clinical practice of Alzheimer's disease (AD). Chronic kidney disease (CKD) has a potential confounding effect on peripheral protein levels. It is essential to characterize the impact of renal function on AD markers. METHODS: Plasma phospho-tau181 (P-tau181), and neurofilament light (NfL) were assayed via the Simoa HD-X platform in 1189 dementia-free participants from the Shanghai Aging Study (SAS). The estimated glomerular filter rate (eGFR) was calculated. The association between renal function and blood NfL, P-tau181 was analyzed. An analysis of interactions between various demographic and comorbid factors and eGFR was conducted. RESULTS: The eGFR levels were negatively associated with plasma concentrations of NfL and P-tau181 (B = - 0.19, 95% CI - 0.224 to - 0.156, P < 0.001; B = - 0.009, 95% CI - 0.013 to -0.005, P < 0.001, respectively). After adjusting for demographic characteristics and comorbid diseases, eGFR remained significantly correlated with plasma NfL (B = - 0.010, 95% CI - 0.133 to - 0.068, P < 0.001), but not with P-tau181 (B = - 0.003, 95% CI - 0.007 to 0.001, P = 0.194). A significant interaction between age and eGFR was found for plasma NfL (Pinteraction < 0.001). In participants ≥ 70 years and with eGFR < 60 ml/min/1.73 m2, the correlation between eGFR and plasma NfL was significantly remarkable (B = - 0.790, 95% CI - 1.026 to - 0,554, P < 0.001). CONCLUSIONS: Considering renal function and age is crucial when interpreting AD biomarkers in the general aging population.


Subject(s)
Alzheimer Disease , Ascorbic Acid , Intermediate Filaments , Aged , Humans , Aging , Amyloid beta-Peptides , Ascorbic Acid/analogs & derivatives , Biomarkers , China , Kidney , tau Proteins
18.
Adv Mater ; 36(19): e2309940, 2024 May.
Article in English | MEDLINE | ID: mdl-38373410

ABSTRACT

The optoelectronic synaptic devices based on two-dimensional (2D) materials offer great advances for future neuromorphic visual systems with dramatically improved integration density and power efficiency. The effective charge capture and retention are considered as one vital prerequisite to realizing the synaptic memory function. However, the current 2D synaptic devices are predominantly relied on materials with artificially-engineered defects or intricate gate-controlled architectures to realize the charge trapping process. These approaches, unfortunately, suffer from the degradation of pristine materials, rapid device failure, and unnecessary complication of device structures. To address these challenges, an innovative gate-free heterostructure paradigm is introduced herein. The heterostructure presents a distinctive dome-like morphology wherein a defect-rich Fe7S8 core is enveloped snugly by a curved MoS2 dome shell (Fe7S8@MoS2), allowing the realization of effective photocarrier trapping through the intrinsic defects in the adjacent Fe7S8 core. The resultant neuromorphic devices exhibit remarkable light-tunable synaptic behaviors with memory time up to ≈800 s under single optical pulse, thus demonstrating great advances in simulating visual recognition system with significantly improved image recognition efficiency. The emergence of such heterostructures foreshadows a promising trajectory for underpinning future synaptic devices, catalyzing the realization of high-efficiency and intricate visual processing applications.

19.
Dalton Trans ; 52(45): 17011-17018, 2023 Nov 21.
Article in English | MEDLINE | ID: mdl-37933580

ABSTRACT

The energy transfer of Ce3+-Eu2+ can often greatly increase the luminescence efficiency and expand the scope of application. In this study, blue to cyan color-tunable phosphors BaCa13Mg2(SiO4)8:Ce3+,Eu2+ were prepared. BaCa13Mg2(SiO4)8:Eu2+ cyan phosphors have limited applications in WLEDs because of their disadvantages, including the inadequate luminescence performance and imperfect matching of UV chips. Therefore, Ce3+ ions were used as sensitizers to enhance the optical performance of Eu2+ ions. The energy transfer efficiency between Ce3+ and Eu2+ in the BaCa13Mg2(SiO4)8 host was calculated to be 96.7%, and the incorporation of Ce3+ ions boosted the integrated intensity and quantum efficiency of the emission spectrum by approximately 80% and 20%, respectively. At 140 °C, the integral emission intensities could still keep at 81.5% of the initial integral intensities at 25 °C. The Ce3+, Eu2+ co-doped cyan phosphor-based WLED lamp could produce outstanding warm white light with CIE coordinates of (0.3722, 0.3222), demonstrating the enormous potential for WLED applications.

20.
Spectrochim Acta A Mol Biomol Spectrosc ; 287(Pt 2): 122126, 2023 Feb 15.
Article in English | MEDLINE | ID: mdl-36423420

ABSTRACT

Inhibiting energy migration between Eu3+ ions in a fixed host to get higher doping concentration is a permanent topic. Herein, a novel non-concentration quenching red-emitting K7SrY2-2xB15O30: xEu3+ (0.1 ≤ x ≤ 1.0) phosphor was synthesized via high-temperature sintering method. XRD measurement, Rietveld refinement results, and radius percentage deviation calculation demonstrated the phase purity and the occupation preference of Eu3+ ions. With continuously increasing doping Eu3+ ions, the absence of concentration quenching could be explained by long distance between two Eu3+ (7.012 Å) and the K7SrEu2B15O30 could exhibit striking photoluminescence performance with the highest emission wavelength centered at 617 nm. Meanwhile, under the radiation of 393 nm, the high internal quantum efficiency ( âˆ¼ 78.71 %), excellent color purity ( âˆ¼ 88.32 %) and robust thermal stability whose emission intensity at 140 °C could still reach âˆ¼ 97.31 % could guarantee its potential application. When coating BaMgAl10O17: Eu2+, (Ba, Sr)2SiO4: Eu2+, and K7SrEu2B15O30 on a near-ultraviolet chip, the bright white light with a low correlated color temperature of 4211 K and CIE color coordinates of (0.3675, 0.3556) could be obtained. Taking the analytic results above, the non-concentration quenching K7SrY2B15O30: Eu3+ compound has great potential to act as a candidate for red-emitting phosphors in solid-state lighting field.

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