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1.
Nature ; 603(7901): 470-476, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35236988

RESUMO

Alzheimer's disease has a higher incidence in older women, with a spike in cognitive decline that tracks with visceral adiposity, dysregulated energy homeostasis and bone loss during the menopausal transition1,2. Inhibiting the action of follicle-stimulating hormone (FSH) reduces body fat, enhances thermogenesis, increases bone mass and lowers serum cholesterol in mice3-7. Here we show that FSH acts directly on hippocampal and cortical neurons to accelerate amyloid-ß and Tau deposition and impair cognition in mice displaying features of Alzheimer's disease. Blocking FSH action in these mice abrogates the Alzheimer's disease-like phenotype by inhibiting the neuronal C/EBPß-δ-secretase pathway. These data not only suggest a causal role for rising serum FSH levels in the exaggerated Alzheimer's disease pathophysiology during menopause, but also reveal an opportunity for treating Alzheimer's disease, obesity, osteoporosis and dyslipidaemia with a single FSH-blocking agent.


Assuntos
Doença de Alzheimer , Hormônio Foliculoestimulante , Idoso , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Animais , Densidade Óssea , Cognição , Feminino , Hormônio Foliculoestimulante/metabolismo , Humanos , Camundongos , Termogênese
2.
PLoS Biol ; 22(1): e3002470, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38206965

RESUMO

The bridging integrator 1 (BIN1) gene is an important risk locus for late-onset Alzheimer's disease (AD). BIN1 protein has been reported to mediate tau pathology, but the underlying molecular mechanisms remain elusive. Here, we show that neuronal BIN1 is cleaved by the cysteine protease legumain at residues N277 and N288. The legumain-generated BIN1 (1-277) fragment is detected in brain tissues from AD patients and tau P301S transgenic mice. This fragment interacts with tau and accelerates its aggregation. Furthermore, the BIN1 (1-277) fragment promotes the propagation of tau aggregates by enhancing clathrin-mediated endocytosis (CME). Overexpression of the BIN1 (1-277) fragment in tau P301S mice facilitates the propagation of tau pathology, inducing cognitive deficits, while overexpression of mutant BIN1 that blocks its cleavage by legumain halts tau propagation. Furthermore, blocking the cleavage of endogenous BIN1 using the CRISPR/Cas9 gene-editing tool ameliorates tau pathology and behavioral deficits. Our results demonstrate that the legumain-mediated cleavage of BIN1 plays a key role in the progression of tau pathology. Inhibition of legumain-mediated BIN1 cleavage may be a promising therapeutic strategy for treating AD.


Assuntos
Doença de Alzheimer , Animais , Humanos , Camundongos , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Doença de Alzheimer/patologia , Encéfalo/metabolismo , Clatrina/metabolismo , Endocitose , Camundongos Transgênicos , Proteínas tau/genética , Proteínas tau/metabolismo
3.
J Proteome Res ; 23(5): 1603-1614, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38557073

RESUMO

Sperm capacitation is broadly defined as a suite of biochemical and biophysical changes resulting from the acquisition of fertilization ability. To gain insights into the regulation mechanism of crustacean sperm capacitation, 4D label-free quantitative proteomics was first applied to analyze the changes of sperm in Eriocheir sinensis under three sequential physiological conditions: seminal vesicles (X2), hatched with the seminal receptacle content (X3), and incubated with egg water (X5). In total, 1536 proteins were identified, among which 880 proteins were quantified, with 82 and 224 proteins significantly altered after incubation with the seminal receptacle contents and egg water. Most differentially expressed proteins were attributed to biological processes by Gene Ontology annotation analysis. As the fundamental bioenergetic metabolism of sperm, the oxidative phosphorylation, glycolysis, and the pentose phosphate pathway presented significant changes under the treatment of seminal receptacle contents, indicating intensive regulation for sperm in the seminal receptacle. Additionally, the seminal receptacle contents also significantly increased the oxidation level of sperm, whereas the enhancement of abundance in superoxide dismutase, peroxiredoxin 1, and glutathione S-transferase after incubation with egg water significantly improved the resistance against oxidation. These results provided a new perspective for reproduction studies in crustaceans.


Assuntos
Braquiúros , Proteômica , Capacitação Espermática , Espermatozoides , Animais , Masculino , Braquiúros/metabolismo , Braquiúros/fisiologia , Proteômica/métodos , Capacitação Espermática/fisiologia , Espermatozoides/metabolismo
4.
BMC Plant Biol ; 24(1): 710, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39060989

RESUMO

BACKGROUND: The Diplolepideae are the larger group within the Arthrodontae mosses, characterized by peristomes formed from residual cell walls. It is now understood that these peristomes exhibit diverse hygroscopic movements, playing a crucial role in spore release. However, the exact mechanism behind this movement remains unclear, lacking direct evidence. This study investigated the microscopic and submicroscopic structures of the peristomes in three Diplolepideae species: Hypopterygium fauriei (Besch.), Pylaisia levieri (Müll. Hal.) Arikawa and Regmatodon declinatus (Hook.) Brid. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to reveal the differences in their hygroscopic movement mechanisms. RESULTS: The three species exhibited distinct responses upon wetting: H. fauriei's exostome closed inwards, P. levieri' opened outwards, and R. declinatus' elongated significantly. These differences are attributed to the varying microfibril deposition in the exostome layers. Uniform deposition in the inner layer and minimal deposition in the outer layer enabled exostome opening upon wetting and closing when dry. Our findings suggest that the diastole and contraction of fine microfibrils in the exostome plates and ridges are the key drivers of hygroscopic movement. CONCLUSIONS: This study provides further evidence at both the structural and submicroscopic levels, contributing to the unraveling of the hygroscopic movement mechanism in Diplolepideae peristomes. This enhanced understanding sheds light on the relationship between peristome structure and function.


Assuntos
Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Molhabilidade , Movimento
5.
Microb Pathog ; 197: 107062, 2024 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-39442811

RESUMO

The widespread prevalence of bovine coronavirus (BCoV) disease worldwide has impacted the livestock industry economically. No effective vaccine is available in China. In this study, we produced BCoV virus-like particles (VLPs) containing E, M, N, S, and hemagglutinin-esterase (HE) proteins using a baculovirus expression system. Five recombinant baculoviruses were co-infected with Sf9 cells, and the VLPs were assembled and characterized. Mice and cattle were immunized by VLPs mixed with MF59 and CpG 55.2 adjuvants. Two doses of the VLPs/MF59/CpG vaccine were administered in mice and cattle. The immune effect of the VLPs/MF59/CpG vaccine was measured using indirect ELISA and neutralization assays. After immunization, the serum IgG-specific antibody titer against S protein and neutralization antibody titer increased to 1:1.28 × 104 (p < 0.01) and 1:128 (p < 0.01) in mice, respectively. Interestingly, the high IgG antibody and neutralizing antibody titers were maintained for seven days in mice. In addition, the serum IgG-specific antibody titer against S proteins and neutralization antibody titer increased to 1:1.024 × 105 and 1:512 (p < 0.05) in cattle, respectively. The high IgG antibody and neutralizing antibody titers were maintained for 21 days in cattle. Notably, BCoV VLPs group interferon-gamma (IFN-γ) lymphocytes in spleens were significantly increased (p < 0.01). These findings suggest that BCoV VLPs induced strong cellular and humoral immune responses in mice and cattle. These findings suggest that BCoV VLPs could serve as a potent immunogen for vaccine development.

6.
Environ Res ; 242: 117739, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38007076

RESUMO

In wastewater treatment plants (WWTPs), ammonia oxidation is primarily carried out by three types of ammonia oxidation microorganisms (AOMs): ammonia-oxidizing archaea (AOA), ammonia-oxidizing bacteria (AOB), and comammox (CMX). Antibiotic resistance genes (ARGs), which pose an important public health concern, have been identified at every stage of wastewater treatment. However, few studies have focused on the impact of ARGs on ammonia removal performance. Therefore, our study sought to investigate the effect of the representative multidrug-resistant plasmid RP4 on the functional microorganisms involved in ammonia oxidation. Using an inhibitor-based method, we first evaluated the contributions of AOA, AOB, and CMX to ammonia oxidation in activated sludge, which were determined to be 13.7%, 41.1%, and 39.1%, respectively. The inhibitory effects of C2H2, C8H14, and 3,4-dimethylpyrazole phosphate (DMPP) were then validated by qPCR. After adding donor strains to the sludge, fluorescence in situ hybridization (FISH) imaging analysis demonstrated the co-localization of RP4 plasmids and all three AOMs, thus confirming the horizontal gene transfer (HGT) of the RP4 plasmid among these microorganisms. Significant inhibitory effects of the RP4 plasmid on the ammonia nitrogen consumption of AOA, AOB, and CMX were also observed, with inhibition rates of 39.7%, 36.2%, and 49.7%, respectively. Moreover, amoA expression in AOB and CMX was variably inhibited by the RP4 plasmid, whereas AOA amoA expression was not inhibited. These results demonstrate the adverse environmental effects of the RP4 plasmid and provide indirect evidence supporting plasmid-mediated conjugation transfer from bacteria to archaea.


Assuntos
Archaea , Betaproteobacteria , Archaea/genética , Archaea/metabolismo , Esgotos/microbiologia , Amônia , Nitrogênio/metabolismo , Desnitrificação , Hibridização in Situ Fluorescente , Oxirredução , Bactérias/genética , Bactérias/metabolismo , Plasmídeos/genética , Betaproteobacteria/genética , Betaproteobacteria/metabolismo , Antibacterianos , Filogenia , Microbiologia do Solo
7.
J Appl Toxicol ; 44(9): 1403-1415, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38778435

RESUMO

Beryllium sulfate (BeSO4) can cause inflammation through the mechanism, which has not been elucidated. Mitochondrial DNA (mtDNA) is a key contributor of inflammation. With mitochondrial damage, released mtDNA can bind to specific receptors (e.g., cGAS) and then activate related pathway to promote inflammatory responses. To investigate the mechanism of mtDNA in BeSO4-induced inflammatory response in 16HBE cells, we established the BeSO4-induced 16HBE cell inflammation model and the ethidium bromide (EB)-induced ρ016HBE cell model to detect the mtDNA content, oxidative stress-related markers, mitochondrial membrane potential, the expression of the cGAS-STING pathway, and inflammation-related factors. Our results showed that BeSO4 caused oxidative stress, decline of mitochondrial membrane potential, and the release of mtDNA into the cytoplasm of 16HBE cells. In addition, BeSO4 induced inflammation in 16HBE cells by activating the cGAS-STING pathway. Furthermore, mtDNA deletion inhibited the expression of cGAS-STING pathway, IL-10, TNF-α, and IFN-ß. This study revealed a novel mechanism of BeSO4-induced inflammation in 16HBE cells, which contributes to the understanding of the molecular mechanism of beryllium and its compounds-induced toxicity.


Assuntos
Berílio , DNA Mitocondrial , Inflamação , Proteínas de Membrana , Nucleotidiltransferases , Transdução de Sinais , Humanos , DNA Mitocondrial/efeitos dos fármacos , DNA Mitocondrial/metabolismo , Nucleotidiltransferases/metabolismo , Nucleotidiltransferases/genética , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Inflamação/induzido quimicamente , Inflamação/metabolismo , Berílio/toxicidade , Transdução de Sinais/efeitos dos fármacos , Linhagem Celular , Estresse Oxidativo/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos
8.
Ecotoxicol Environ Saf ; 272: 116039, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38310822

RESUMO

Mosses are an integral component in the tufa sedimentary landscape. In this study, we investigated the use of the porous moss-tufa structure as a filtration system for removing potentially toxic elements (PTEs) from water samples. Three species of mosses that commonly grow on tufa were selected, and the PTEs filtered by the moss-tufa system were identified by inductively coupled plasma mass spectrometry. The bioconcentration factor (BCF) of mosses was calculated to compare the enrichment effects of different mosses on PTEs. Likewise, the level of PTEs flowing through the moss-tufa system was measured, and the water quality removal rate (C) was calculated accordingly. The results revealed that the moss-tufa system was mainly composed of Fissidens grandifrons Brid., Hydrogonium dixonianum P. C. Chen, and Cratoneuron filicinum (Hedw.) Spruce var. filicinum. Among these, Fissidens grandifrons Brid. reported the highest retention capacity for PTEs. Collectively, the moss-tufa filtration system displayed a strong retention capacity and removal rate of Mn, Pb, and Ni from the water sample. The removal of PTEs by the moss-tufa system was mainly based on the enrichment of mosses and the adsorption-retention ability of tufa. In conclusion, the moss-tufa micro-filtration system displayed the effective removal of PTEs from water samples and could be applied to control the levels of toxic elements in karst water bodies.


Assuntos
Briófitas , Bryopsida , Metais Pesados , Metais Pesados/análise , Monitoramento Ambiental/métodos , Bryopsida/química , Medição de Risco
9.
Int J Phytoremediation ; 26(9): 1526-1536, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38525911

RESUMO

Bauxite residue (BR) is a large volume by-product generated during bauxite smelting process and metal pollution problem is becoming increasingly prominent in residue areas. Accumulation and transfer of metals in six vascular plants were analyzed and soil environment was evaluated. Results found levels of Al (2,110-26,280 mg kg-1), Fe (990 to 9,880 mg kg-1), Ca (8,020 to 49,250 mg kg-1), Mg (2,060 to 17,190 mg kg-1), K (16,840 to 39,670 mg kg-1), and Ti (80 to 1,240 mg kg-1) in plants. Metal concentrations in soils exceeded background levels. Bioconcentration factor (BCF) found that Al, Fe, and Ti in plants (roots, stems, and leaves) were relatively depleted (BCF <1). Transfer factor (TF) of Al, Fe, Ca, K, and Ti in plants was distinctly higher than 1 and mainly concentrated in stems and leaves. Pollution indices revealed that soil environment was at moderated to serious contaminated risk. Principal components analysis (PCA) showed that Artemisia caruifolia Buch. and Siegesbeckia orientalis L. plants had a good ability to absorb Al and Fe, which can be used as biological indicators and restoration materials.


Currently, soil environment was exposed to moderated to serious contaminated risk from Wachangping karst bauxite residue areas.Bioconcentration factor (BCF) analysis found that Al, Fe, and Ti in six vascular plants (roots, stems, and leaves) were relatively depleted (BCF <1).Transfer factor (TF) of Al, Fe, Ca, K, and Ti in vascular plants was distinctly higher than 1, which mainly concentrated in stems and leaves.PCA revealed that Artemisia caruifolia Buch. and Siegesbeckia orientalis L. plants had a good ability to absorb Al and Fe, which can be used as biological indicators and ecological restoration materials.


Assuntos
Óxido de Alumínio , Poluentes do Solo , Poluentes do Solo/metabolismo , Poluentes do Solo/análise , Bioacumulação , Biodegradação Ambiental , China , Solo/química , Metais/metabolismo , Metais Pesados/metabolismo , Metais Pesados/análise , Monitoramento Ambiental , Folhas de Planta/metabolismo
10.
Neuromodulation ; 27(2): 273-283, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36801128

RESUMO

OBJECTIVE: Functional dyspepsia (FD), which has a complicated pathophysiologic process, is a common functional gastrointestinal disease. Gastric hypersensitivity is the key pathophysiological factor in patients with FD with chronic visceral pain. Auricular vagal nerve stimulation (AVNS) has the therapeutic effect of reducing gastric hypersensitivity by regulating the activity of the vagus nerve. However, the potential molecular mechanism is still unclear. Therefore, we investigated the effects of AVNS on the brain-gut axis through the central nerve growth factor (NGF)/ tropomyosin receptor kinase A (TrkA)/phospholipase C-gamma (PLC-γ) signaling pathway in FD model rats with gastric hypersensitivity. MATERIALS AND METHODS: We established the FD model rats with gastric hypersensitivity by means of colon administration of trinitrobenzenesulfonic acid on ten-day-old rat pups, whereas the control rats were given normal saline. AVNS, sham AVNS, K252a (an inhibitor of TrkA, intraperitoneally), and K252a + AVNS were performed on eight-week-old model rats for five consecutive days. The therapeutic effect of AVNS on gastric hypersensitivity was determined by the measurement of abdominal withdrawal reflex response to gastric distention. NGF in gastric fundus and NGF, TrkA, PLC-γ, and transient receptor potential vanilloid 1 (TRPV1) in the nucleus tractus solitaries (NTS) were detected separately by polymerase chain reaction, Western blot, and immunofluorescence tests. RESULTS: It was found that a high level of NGF in gastric fundus and an upregulation of the NGF/TrkA/PLC-γ signaling pathway in NTS were manifested in model rats. Meanwhile, both AVNS treatment and the administration of K252a not only decreased NGF messenger ribonucleic acid (mRNA) and protein expressions in gastric fundus but also reduced the mRNA expressions of NGF, TrkA, PLC-γ, and TRPV1 and inhibited the protein levels and hyperactive phosphorylation of TrkA/PLC-γ in NTS. In addition, the expressions of NGF and TrkA proteins in NTS were decreased significantly after the immunofluorescence assay. The K252a + AVNS treatment exerted a more sensitive effect on regulating the molecular expressions of the signal pathway than did the K252a treatment. CONCLUSION: AVNS can regulate the brain-gut axis effectively through the central NGF/TrkA/PLC-γ signaling pathway in the NTS, which suggests a potential molecular mechanism of AVNS in ameliorating visceral hypersensitivity in FD model rats.


Assuntos
Dispepsia , Estimulação do Nervo Vago , Animais , Ratos , Dispepsia/terapia , Fator de Crescimento Neural/metabolismo , Fosfolipase C gama/metabolismo , Receptor trkA/genética , Receptor trkA/metabolismo , RNA Mensageiro , Transdução de Sinais , Tropomiosina/metabolismo
11.
J Environ Manage ; 361: 121238, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38815424

RESUMO

To elucidate the mechanisms and effects of phosphorus (P) desorption on P fractions in soil aggregates of revegetated ecosystems is fundamental for regulating the P supply and biogeochemical cycle. We selected four aggregate sizes (1-5, 0.5-1, 0.25-0.5, and <0.25 mm) from a desert revegetation chronosequence (11, 31, 40, 57, and 65 years) as our study targets and used the Freundlich model to reveal the dynamics of P desorption and changes in P fractions. The results showed that the calibrated model [Formula: see text] for different size aggregates in seven deserts (two natural and five revegetated) described the P desorption characteristics well. In soil aggregates of revegetated deserts, smaller aggregates with higher specific surface area did not desorb more P, nor did older aggregates after revegetation. The natural P desorption process in aggregates resulted in significant changes in Ca2-P, Ca8-P, Al-P and Fe-P fractions (p < 0.05), and revegetation years also affected P fraction dynamics significantly (p < 0.05). This study highlights that the calibrated kinetic model in the revegetated soil aggregates elucidated the P desorption characteristics, and that the P desorption process drove P fraction changes.


Assuntos
Ecossistema , Fósforo , Solo , Fósforo/química , Solo/química
12.
BMC Nurs ; 23(1): 559, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39135197

RESUMO

BACKGROUND: Given increases in China's aging population, the growing demand for public health services and the shortage of human resources among nurses have become more prominent. Under such a background, "Internet + Nursing Services" have received more attention. Thus, exploring the barriers to and facilitators of nurses' willingness to participate in "Internet + Nursing Services" and utilizing internet technology to increase the supply of nursing services has become a key issue. OBJECTIVE: This study aimed to develop a scale for assessing the barriers to and facilitators of nurses' willingness to participate in "Internet + Nursing Services" and to test the validity and reliability of the scale. METHODS: A preliminary scale was developed based on a literature review, theoretical research, semistructured qualitative interviews, and two rounds of Delphi expert inquiry. A convenient sampling method was used for the questionnaire survey. A 5-point Likert scale was used to evaluate the importance of the items. The survey data of 659 clinical nurses obtained from February to March 2023 were used for item analysis, exploratory factor analysis (EFA), and reliability and validity tests of the scale. The survey data of 538 clinical nurses obtained in April 2023 were used for confirmatory factor analysis (CFA) of the final scale. RESULTS: The final scale consists of 25 items and 4 dimensions (performance expectations, perceived risk, need for professional knowledge training, and nonprofessional knowledge training). The scale showed good structural validity and content validity: the Cronbach's α coefficient of the scale was 0.955, the split-half reliability was 0.778, the test-retest reliability was 0.944, the kaiser-meyer-olkin(KMO) value was 0.960, and the cumulative variance contribution rate of the 4 common factors was 83.147%. The scale content validity index(S-CVI) was 0.914. The confirmatory factor analysis model had favorable fit indices: χ2/df = 4.234, RMSEA = 0.078, NFI = 0.940, IFI = 0.953, TLI = 0.947, and CFI = 0.953. CONCLUSION: The scale for assessing the barriers to and facilitators of nurses' willingness to participate in "Internet + Nursing Services" has good reliability and validity, and provides a reference for evaluating nurses' willingness to participate in "Internet + Nursing Services".

13.
Environ Geochem Health ; 46(10): 381, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39167155

RESUMO

Potentially toxic elements (PTEs) pose a significant threat to aquatic ecosystems. This study investigated the content and potential sources of PTEs (Cr, Mn, Ni, Cu, Zn, Cd, Pb) in water, sediment, and dominant aquatic plants (Hydrilla verticillata and Spirogyra varians) in the Xiaojiang River, located near the Zhaiying manganese mine in Guizhou Province, China. Correlation analysis, principal component analysis (PCA), and cluster analysis were employed to assess PTE distribution and potential sources. Water PTE concentrations complied with the Class II standard (GB3838-2002), indicating no water pollution. However, sediment PTE levels exceeded background values, particularly Mn, which exhibited moderate to strong contamination. Cd also showed moderate contamination, posing a considerable ecological risk. Cd was the main potential pollutant with the highest contribution rate. Mn and Cd were therefore identified as priority pollutants requiring targeted abatement strategies. Mining activities likely represent the primary source, but combined pollution from vehicle traffic and agriculture might also contribute. Hydrilla verticillata demonstrated a higher capacity for PTE enrichment from sediment compared to Spirogyra varians, suggesting its potential for sediment remediation (except for Cu). A significant correlation existed between both plant species and sediment PTE content. PCA supported the association between S. varians and sediment PTEs. Linear regression analyses revealed better correlations between S. varians and sediment Mn, Ni, Cu, and Zn (0.77, 0.68, 0.82, and 0.79, respectively). Taken together, these findings suggest that S. varians serves as an effective bioindicator for monitoring sediment contamination with PTEs.


Assuntos
Monitoramento Ambiental , Sedimentos Geológicos , Hydrocharitaceae , Manganês , Mineração , Rios , Spirogyra , Poluentes Químicos da Água , Poluentes Químicos da Água/análise , China , Manganês/análise , Sedimentos Geológicos/química , Rios/química , Hydrocharitaceae/metabolismo , Monitoramento Ambiental/métodos , Spirogyra/metabolismo , Bioacumulação , Metais Pesados/análise , Análise de Componente Principal
14.
Yi Chuan ; 46(7): 511-529, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39016085

RESUMO

Sperm chromatin not only carries genetic information such as paternal DNA, but also carries structural proteins, epigenetic information, and higher-order chromatin structures (such as matrix attachment regions and telomeres), etc. These information play an important role in embryonic development. This article mainly reviews the effects of these different information carried by sperm chromatin on sperm function and embryonic development and the research progress of related detection methods, in order to provide a theoretical basis and scientific diagnosis and treatment strategies for the etiology screening of clinical infertility, embryo arrest and recurrent miscarriage, so as to improve the pregnancy outcomes of natural conception and assisted reproduction. Keywords: sperm chromatin; epigenetics; sperm DNA damage; sperm function; higher-order chromatin structures.


Assuntos
Cromatina , Espermatozoides , Cromatina/genética , Cromatina/metabolismo , Masculino , Espermatozoides/fisiologia , Espermatozoides/metabolismo , Humanos , Animais , Dano ao DNA , Epigênese Genética , Feminino
15.
Anal Chem ; 95(49): 18139-18148, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38013435

RESUMO

Herein, a dual-nanozyme cascade catalysis triemission fluorescence capillary imprinted sensor integrated with intelligent logic gates was constructed for simultaneous detection of 2,4-dichlorophenoxyacetic acid (2,4-DA) and 2,4-dichlorophenol (2,4-DCP). The novel nanozyme fluorescence organic framework (Bi, Co-MOF) was grafted on the surface of Fe3O4 modified with histidine to form a nanozyme composite (FBM) with dual-enzyme activity, which was imprinted with 2,4-DA to prepare a fluorescence molecularly imprinted polymer (FBM@MIP). Carbon dots (CDs) coupling with FBM@MIP (FBM@MIP/CDs) was inhaled into a capillary to construct a dual-nanozyme capillary imprinted sensor directly. The FBM@MIP/CDs capillary sensor realized to detect 2,4-DA and 2,4-DCP simultaneously within a linear concentration range of 1.0 × 10-12-1.2 × 10-9 M and 1.0 × 10-12-4.8 × 10-9 M with the detection limit of 0.75 and 0.68 pM, respectively. Interestingly, a smartphone-assisted portable capillary fluorescence intelligent sensing platform was developed that can detect 2,4-DA and 2,4-DCP visually without tedious operations such as soaking and drying. Combined with a smartphone, the linear relationships between RGB ratios and concentrations of 2,4-DA and 2,4-DCP were established with the detection limit of 0.93 and 0.81 pM, respectively. The integrated logic gates provided a promising way for intelligent sensing of multiple targets simultaneously, which provided a new strategy for ultrasensitive simultaneous detection of multiple pollutants with a microvolume (18 µL/time) in complex environments.

16.
Opt Express ; 31(14): 23693-23701, 2023 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-37475448

RESUMO

The Brewster effect has been previously reported as an essential mechanism for terahertz (THz) wave sensing application. However, generally in a sensing application, a complex rotation apparatus is required for detecting the slight change in Brewster angle. Here, we propose a graphene-based Brewster angle device operating at a specific terahertz frequency capable of sensing the refractive index at a fixed incident angle. In other words, our sensing device could avoid the impact of Brewster angle shift and eliminate the need for high-precision rotating equipment, which is usually required in traditional sensing applications. The conversion from the refractive index to a Volt-level detectable voltage roots from the tunability of graphene's Fermi level in the external electrical field. A linear correlation between the output voltage and the background refractive index is observed and theocratically analyzed. Furthermore, we present the improvement of our device in terms of sensing range and sensitivity by adjusting the permittivity of the dielectric substrate. As a demonstration of our proposed device, a detection range of 1.1-2.4 and a sensitivity of 20.06 V/RIU for refractive index is achieved on a high-resistance silicon substrate operating at 0.3 THz.

17.
Mov Disord ; 38(11): 2005-2018, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37593929

RESUMO

BACKGROUND: The accumulation and aggregation of α-synuclein (α-Syn) are characteristic of Parkinson's disease (PD). Epidemiological evidence indicates that hyperlipidemia is associated with an increased risk of PD. The levels of 27-hydroxycholesterol (27-OHC), a cholesterol oxidation derivative, are increased in the brain and cerebrospinal fluid of patients with PD. However, whether 27-OHC plays a role in α-Syn aggregation and propagation remains elusive. OBJECTIVE: The aim of this study was to determine whether 27-OHC regulates α-Syn aggregation and propagation. METHODS: Purified recombinant α-Syn, neuronal cultures, and α-Syn fibril-injected mouse model of PD were treated with 27-OHC. In addition, CYP27A1 knockout mice were used to investigate the effect of lowering 27-OHC on α-Syn pathology in vivo. RESULTS: 27-OHC accelerates the aggregation of α-Syn and enhances the seeding activity of α-Syn fibrils. Furthermore, the 27-OHC-modified α-Syn fibrils localize to the mitochondria and induce mitochondrial dysfunction and neurotoxicity. Injection of 27-OHC-modified α-Syn fibrils induces enhanced spread of α-Syn pathology and dopaminergic neurodegeneration compared with pure α-Syn fibrils. Similarly, subcutaneous administration of 27-OHC facilitates the seeding of α-Syn pathology. Genetic deletion of cytochrome P450 27A1 (CYP27A1), the enzyme that converts cholesterol to 27-OHC, ameliorates the spread of pathologic α-Syn, degeneration of the nigrostriatal dopaminergic pathway, and motor impairments. These results indicate that the cholesterol metabolite 27-OHC plays an important role in the pathogenesis of PD. CONCLUSIONS: 27-OHC promotes the aggregation and spread of α-Syn. Strategies aimed at inhibiting the CYP27A1-27-OHC axis may hold promise as a disease-modifying therapy to halt the progression of α-Syn pathology in PD. © 2023 International Parkinson and Movement Disorder Society.


Assuntos
Doença de Parkinson , Humanos , Camundongos , Animais , Doença de Parkinson/genética , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo , Hidroxicolesteróis/farmacologia , Colesterol
18.
Brain ; 145(10): 3454-3471, 2022 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-35552614

RESUMO

The aggregation and prion-like propagation of α-synuclein are involved in the pathogenesis of Parkinson's disease. However, the underlying mechanisms regulating the assembly and spreading of α-synuclein fibrils remain poorly understood. Tau co-deposits with α-synuclein in the brains of Parkinson's disease patients, suggesting a pathological interplay between them. Here we show that tau interacts with α-synuclein and accelerates its aggregation. Compared with pure α-synuclein fibrils, the tau-modified α-synuclein fibrils show enhanced seeding activity, inducing mitochondrial dysfunction, synaptic impairment and neurotoxicity in vitro. Injection of the tau-modified α-synuclein fibrils into the striatum of mice induces more severe α-synuclein pathology, motor dysfunction and cognitive impairment when compared with the mice injected with pure α-synuclein fibrils. Knockout of tau attenuates the propagation of α-synuclein pathology and Parkinson's disease-like symptoms both in mice injected with α-syn fibrils and α-syn A53T transgenic mice. In conclusion, tau facilitates α-synuclein aggregation and propagation in Parkinson's disease.


Assuntos
Doença de Parkinson , Príons , Sinucleinopatias , Animais , Camundongos , alfa-Sinucleína , Doença de Parkinson/patologia , Camundongos Knockout , Camundongos Transgênicos
19.
Appl Opt ; 62(5): 1167-1174, 2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36821214

RESUMO

A quantitative analysis method for corrosion products based on terahertz spectroscopy is proposed in this paper. Mixture samples consisting of three major corrosion products (magnetite, hematite, and goethite) were prepared in 51 different concentrations. The refractive index spectra measured by terahertz time-domain spectroscopy were projected to the 2D score diagram by performing principal component analysis. The Euclidean distances between the mixtures and pure analyte on the diagram were used to build a concentration prediction model. The results indicate that the established model can precisely predict the concentration of magnetite, which is essential for a stability evaluation of the corrosion system.

20.
J Appl Toxicol ; 43(8): 1169-1182, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36843388

RESUMO

Beryllium sulfate (BeSO4 ) can result to lung injuries, such as leading to lipid peroxidation and autophagy, and the treatment of beryllium disease has not been well improved. Ferroptosis is a regulated cell death process driven by iron-dependent and lipid peroxidation, while ferritinophagy is a process mediated by nuclear receptor coactivator 4 (NCOA4), combined with ferritin heavy chain 1 (FTH1) degradation and release Fe2+ , which regulated intracellular iron metabolism and ferroptosis. Hydrogen sulfide (H2 S) has the effects of antioxidant, antiautophagy, and antiferroptosis. This study aimed to investigate the effect of H2 S on BeSO4 -induced ferroptosis and ferritinophagy in 16HBE cells and the underlying mechanism. In this study, BeSO4 -induced 16HBE cell injury model was established based on cellular level and pretreated with deferoxamine (DFO, a ferroptosis inhibitor), sodium hydrosulfide (NaHS, a H2 S donor), or NCOA4 siRNA and, subsequently, performed to detect the levels of lipid peroxidation and Fe2+ and the biomarkers of ferroptosis and ferritinophagy. More importantly, our research found that DFO, NaHS, or NCOA4 siRNA alleviated BeSO4 -induced ferroptosis and ferritinophagy by decreasing the accumulation of Fe2+ and lipid peroxides. Furthermore, the relationship between ferroptosis, ferritinophagy, H2 S, and beryllium disease is not well defined; therefore, our research is innovative. Overall, our results provided a new theoretical basis for the prevention and treatment of beryllium disease and suggested that the application of H2 S, blocking ferroptosis, and ferritinophagy may be a potential therapeutic direction for the prevention and treatment of beryllium disease.


Assuntos
Beriliose , Ferroptose , Sulfeto de Hidrogênio , Humanos , Sulfeto de Hidrogênio/farmacologia , Autofagia , Ferro/toxicidade , RNA Interferente Pequeno , Fatores de Transcrição
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