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1.
Nat Commun ; 15(1): 3289, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38632231

RESUMO

Endowing textiles with perceptual function, similar to human skin, is crucial for the development of next-generation smart wearables. To date, the creation of perceptual textiles capable of sensing potential dangers and accurately pinpointing finger touch remains elusive. In this study, we present the design and fabrication of intelligent perceptual textiles capable of electrically responding to external dangers and precisely detecting human touch, based on conductive silk fibroin-based ionic hydrogel (SIH) fibers. These fibers possess excellent fracture strength (55 MPa), extensibility (530%), stable and good conductivity (0.45 S·m-1) due to oriented structures and ionic incorporation. We fabricated SIH fiber-based protective textiles that can respond to fire, water, and sharp objects, protecting robots from potential injuries. Additionally, we designed perceptual textiles that can specifically pinpoint finger touch, serving as convenient human-machine interfaces. Our work sheds new light on the design of next-generation smart wearables and the reshaping of human-machine interfaces.


Assuntos
Fibroínas , Seda , Humanos , Seda/química , Têxteis , Condutividade Elétrica , Fibroínas/química , Tato
2.
Carbohydr Polym ; 335: 122084, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38616102

RESUMO

Mapping the N-glycome of porcine sperm before and after sperm capacitation is important for understanding the rearrangement of glycoconjugates during capacitation. In this work, we characterized the N-glycome on the membranes of 18 pairs of fresh porcine sperm before capacitation and porcine sperm after capacitation by MALDI-MS (Matrix-assisted laser desorption/ionization-mass spectrometry). A total of 377 N-glycans were detected and a comprehensive N-glycome map of porcine sperm membranes before and after capacitation was generated, which presents the largest N-glycome dataset of porcine sperm cell membranes. Statistical analysis revealed a significantly higher level of high mannose glycosylation and a significantly lower level of fucosylation, galactosylation, and α-2,6-NeuAc after capacitation, which is further verified by flow cytometry and lectin blotting. This research reveals new insights into the relationship between N-glycosylation variations and sperm capacitation, including the underlying mechanisms of the capacitation process.


Assuntos
Peróxido de Benzoíla , Sêmen , Masculino , Suínos , Animais , Membranas , Membrana Celular , Espermatozoides
3.
Nat Commun ; 15(1): 2997, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589397

RESUMO

Cell surface proteins are responsible for many crucial physiological roles, and they are also the major category of drug targets as the majority of therapeutics target membrane proteins on the surface of cells to alter cellular signaling. Despite its great significance, ligand discovery against membrane proteins has posed a great challenge mainly due to the special property of their natural habitat. Here, we design a new chemical proteomic probe OPA-S-S-alkyne that can efficiently and selectively target the lysines exposed on the cell surface and develop a chemical proteomics strategy for global analysis of surface functionality (GASF) in living cells. In total, we quantified 2639 cell surface lysines in Hela cell and several hundred residues with high reactivity were discovered, which represents the largest dataset of surface functional lysine sites to date. We discovered and validated that hyper-reactive lysine residues K382 on tyrosine kinase-like orphan receptor 2 (ROR2) and K285 on Endoglin (ENG/CD105) are at the protein interaction interface in co-crystal structures of protein complexes, emphasizing the broad potential functional consequences of cell surface lysines and GASF strategy is highly desirable for discovering new active and ligandable sites that can be functionally interrogated for drug discovery.


Assuntos
Lisina , Proteômica , Humanos , Lisina/metabolismo , Células HeLa , Ligantes , Endoglina
4.
Anal Chem ; 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38666489

RESUMO

Quantitative glycosylation analysis serves as an effective tool for detecting changes in glycosylation patterns in cancer and various diseases. However, compared with N-glycans, O-glycans present challenges in both qualitative and quantitative mass spectrometry analysis due to their low abundance, ease of peeling, lack of a universal enzyme, and difficult accessibility. To address this challenge, we developed O-GlycoIsoQuant, a novel O-glycome quantitative approach utilizing superbase release and isotopic Girard's P labeling. This method facilitates rapid and efficient nonreducing ß-elimination to dissociate O-glycans from proteins using the organic superbase, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), combined with light and heavy isotopic Girard's reagent P (GP) labeling for relative quantification of O-glycans by mass spectrometry. Employing this method, labeled O-glycans exhibit a double peak with a mass difference of 5 Da, suitable for stable relative quantification. The O-GlycoIsoQuant method is characterized by its high labeling efficiency, excellent reproducibility (CV < 20%), and good linearity (R2 > 0.99), across a dynamic range spanning a 100-fold range. This method was applied to various complex sample types, including human serum, porcine spermatozoa, human saliva, and urinary extracellular vesicles, detecting 33, 39, 49, and 37 O-glycans, respectively, thereby demonstrating its broad applicability.

5.
Anal Chem ; 96(13): 5125-5133, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38502245

RESUMO

Protein modification by lipid-derived electrophiles (LDEs) is associated with various signaling pathways. Among these LDEs, 4-hydroxy-2-nonenal (HNE) is the most toxic, and protein modified with HNE has been linked to various diseases, including Alzheimer's and Parkinson's. However, due to their low abundance, in-depth profiling of HNE modifications still presents challenges. This study introduces a novel strategy utilizing reversible thiazolidine chemistry to selectively capture HNE-modified proteins and a palladium-mediated cleavage reaction to release them. Thousands of HNE-modified sites in different cell lines were identified. Combined with ABPP, we discovered a set of HNE-sensitive sites that offer a new tool for studying LDE modifications in proteomes.


Assuntos
Aldeídos , Processamento de Proteína Pós-Traducional , Tiazolidinas , Aldeídos/metabolismo , Proteoma/metabolismo , Peroxidação de Lipídeos
6.
J Bone Miner Res ; 2024 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-38477752

RESUMO

Observational studies have reported inconsistent associations between bone mineral density (BMD) and coronary artery calcification (CAC). We examined the observational association of BMD with CAC in two large population-based studies and evaluated the evidence for a potential causal relation between BMD and CAC using polygenic risk scores (PRS), 1- and 2-sample Mendelian randomization (MR) approaches. Our study populations comprised 1414 individuals (mean age 69.9 years, 52.0% women) from the Rotterdam Study and 2233 individuals (mean age 56.5 years, 50.9% women) from the Framingham Heart Study with complete information on CAC and BMD measurements at the total body (TB-), lumbar spine (LS-), and femoral neck (FN-). We used linear regression models to evaluate the observational association between BMD and CAC. Subsequently, we compared the mean CAC across PRSBMD quintile groups at different skeletal sites. In addition, we used the 2-stage least squares regression (2SLS) and the inverse variance weighted (IVW) model as primary methods for 1- and 2-sample MR to test evidence for a potentially causal association. We did not observe robust associations between measured BMD levels and CAC. These results were consistent with a uniform random distribution of mean CAC across PRSBMD quintile groups (p-value >0.05). Moreover, neither 1- nor 2-sample MR supported the possible causal association between BMD and CAC. Our results do not support the contention that lower BMD is (causally) associated with an increased CAC risk. These findings suggest that previously reported epidemiological associations of BMD with CAC are likely explained by unmeasured confounders or shared etiology, rather than by causal pathways underlying both osteoporosis and vascular calcification processes.

7.
Cell Rep ; 43(2): 113720, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38308845

RESUMO

LMNA gene mutation can cause muscular dystrophy, and post-translational modification plays a critical role in regulating its function. Here, we identify that lamin A is palmitoylated at cysteine 522, 588, and 591 residues, which are reversely catalyzed by palmitoyltransferase zinc finger DHHC-type palmitoyltransferase 5 (ZDHHC5) and depalmitoylase α/ß hydrolase domain 7 (ABHD7). Furthermore, the metabolite lactate promotes palmitoylation of lamin A by inhibiting the interaction between it and ABHD7. Interestingly, low-level palmitoylation of lamin A promotes, whereas high-level palmitoylation of lamin A inhibits, murine myoblast differentiation. Together, these observations suggest that ABHD7-mediated depalmitoylation of lamin A controls myoblast differentiation.


Assuntos
Lamina Tipo A , Distrofias Musculares , Animais , Camundongos , Diferenciação Celular , Lamina Tipo A/metabolismo , Distrofias Musculares/genética , Mioblastos/metabolismo , Processamento de Proteína Pós-Traducional
8.
Innovation (Camb) ; 5(2): 100565, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38379791

RESUMO

Partial endothelial-to-mesenchymal transition (EndMT) is an intermediate phenotype observed in endothelial cells (ECs) undergoing a transition toward a mesenchymal state to support neovascularization during (patho)physiological angiogenesis. Here, we investigated the occurrence of partial EndMT in ECs under hypoxic/ischemic conditions and identified general transcription factor IIH subunit 4 (GTF2H4) as a positive regulator of this process. In addition, we discovered that GTF2H4 collaborates with its target protein excision repair cross-complementation group 3 (ERCC3) to co-regulate partial EndMT. Furthermore, by using phosphorylation proteomics and site-directed mutagenesis, we demonstrated that GTF2H4 was involved in the phosphorylation of receptor coactivator 3 (NCOA3) at serine 1330, which promoted the interaction between NCOA3 and p65, resulting in the transcriptional activation of NF-κB and the NF-κB/Snail signaling axis during partial EndMT. In vivo experiments confirmed that GTF2H4 significantly promoted partial EndMT and angiogenesis after ischemic injury. Collectively, our findings reveal that targeting GTF2H4 is promising for tissue repair and offers potential opportunities for treating hypoxic/ischemic diseases.

9.
Analyst ; 149(4): 1111-1120, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38170640

RESUMO

Protein S-acylation is an important lipid modification characteristic for heterogeneity in the acyl chain and dynamicity in the acylation/deacylation cycle. Most S-acylproteomic research has been limited by indirect identification of modified proteins/peptides without attached fatty acids, resulting in the failure to precisely characterize S-acylated sites with attached fatty acids. The study of S-acylation turnover is still limited at the protein level. Herein, aiming to site-specifically profile both the heterogeneity and the turnover of S-acylation, we first developed a site-specific strategy for intact S-acylated peptide analysis by introducing an acid cleavable bioorthogonal tag into a metabolic labelling method (ssMLCC). The cleavable bioorthogonal tag allowed for the selective enrichment and efficient MS analysis of intact S-acylated peptides so that S-acylated sites and their attached fatty acids could be directly analysed, enabling the precise mapping of S-acylated sites, as well as circumventing false positives from previous studies. Moreover, 606 S-palmitoylated (C16:0) sites of 441 proteins in HeLa cells were identified. All types of S-acylated peptides were further characterized by an open search, providing site-specific profiling of acyl chain heterogeneity, including S-myristoylation, S-palmitoylation, S-palmitoleylation, and S-oleylation. Furthermore, site-specific monitoring of S-palmitoylation turnover was achieved by coupling with pulse-chase methods, facilitating the detailed observation of the dynamic event at each site in multi-palmitoylated proteins, and 85 rapidly cycling palmitoylated sites in 79 proteins were identified. This study provided a strategy for the precise and comprehensive analysis of protein S-acylation based on intact S-acylated peptide analysis, contributing to the further understanding of its complexity and biological functions.


Assuntos
Ácidos Graxos , Proteínas , Humanos , Células HeLa , Proteínas/metabolismo , Ácidos Graxos/metabolismo , Peptídeos/metabolismo , Acilação
10.
Am J Prev Med ; 66(2): 315-323, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37690589

RESUMO

INTRODUCTION: Given the increase in ultra-processed food (UPF) consumption, their potential health effects have aroused concern. Whether UPF consumption is associated with cancer and cardiovascular disease mortality is debatable. This study evaluates the association of UPF consumption with mortality. METHODS: A total of 108,714 U.S. adults from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (1993-2001), 208,051 UK adults from UK Biobank (2006-2010), and 41,070 U.S. adults from National Health and Nutrition Examination Survey (1999-2018) were included. Dietary data were collected by dietary questionnaire and classified using the NOVA classification. UPF consumption was expressed as the weight proportion of UPFs in total foods consumed. Cox proportional hazard models were used to calculate hazard ratios and 95% CIs. Mediation analysis was used to evaluate whether multiple metabolic pathways mediated the associations in UK Biobank. Analyses were performed in 2022-2023. RESULTS: Combined analyses of the three cohorts showed that those with the highest quartile of UPF consumption had higher risks of all-cause mortality (hazard ratio, 1.16; 95% CI, 1.11-1.20) and cardiovascular disease mortality (hazard ratio, 1.17; 95% CI, 1.06-1.28) compared to the lowest quartile of UPF consumption. UPF consumption was not associated with cancer mortality risk. Biomarkers of liver function have the greatest mediating effects on all-cause mortality (20.3%), and biomarkers of inflammation have the greatest mediating effects on cardiovascular disease mortality (29.2%). CONCLUSIONS: Higher UPF consumption was associated with increased all-cause and cardiovascular disease mortality risk, with multiple metabolic pathways playing mediating roles.


Assuntos
Doenças Cardiovasculares , Neoplasias , Adulto , Humanos , Masculino , Biomarcadores , Estudos de Coortes , Dieta , Fast Foods/efeitos adversos , Manipulação de Alimentos , Alimento Processado , Inquéritos Nutricionais , Reino Unido/epidemiologia , Feminino , Ensaios Clínicos como Assunto
11.
Biochim Biophys Acta Mol Basis Dis ; 1870(2): 166969, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38008231

RESUMO

BACKGROUND: Ferroptosis is a type of non-apoptotic cell death that relies on iron ions and reactive oxygen species to induce lipid peroxidation. This study aimed to determine whether ferroptosis exists in the pathogenesis of dry age-related macular degeneration (AMD) and to confirm that melatonin (MLT) suppresses the photoreceptor cell ferroptosis signaling pathway. METHODS: We exposed 661W cells to sodium iodate (NaIO3) in vitro and treated them with different concentrations of MLT. In vivo, C57BL/6 mice were given a single caudal vein injection of NaIO3, followed by an intraperitoneal injection of MLT, and eyeballs were taken for subsequent trials. RESULTS: We found that NaIO3 could induce photoreceptor cell death and lipid peroxide accumulation, and result in changes in the expression of ferroptosis-related factors and iron maintenance proteins, which were treated by MLT. We further demonstrated that MLT can block Fyn-dependent Nrf2 nuclear translocation by suppressing the GSK-3ß signaling pathway. In addition, the therapeutic effect of MLT was significantly inhibited when Nrf2 was silenced. CONCLUSIONS: Our findings provide a novel insight that NaIO3 induces photoreceptor cell ferroptosis in dry AMD and suggest that MLT has therapeutic effects by suppressing GSK-3ß/Fyn-dependent Nrf2 nuclear translocation.


Assuntos
Ferroptose , Melatonina , Camundongos , Animais , Melatonina/farmacologia , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Glicogênio Sintase Quinase 3 beta/genética , Camundongos Endogâmicos C57BL , Células Fotorreceptoras/metabolismo , Ferro/farmacologia
12.
Sci Bull (Beijing) ; 68(23): 2973-2981, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37798179

RESUMO

Nature-derived silk fibers possess excellent biocompatibility, sustainability, and mechanical properties, yet producing strong and tough silk fibers in a facile and large-scale manner remains a significant challenge. Herein, we report a simple method for preparing strong and tough silk fibers by feeding silkworms rare earth ion-modified diets. The resulting silk fibers exhibit significantly increased tensile strength and toughness, with average values of 0.85 ± 0.07 GPa and 156 ± 13 MJ m-3, respectively, and maximum values of 0.97 ± 0.04 GPa and 188 ± 19 MJ m-3, approaching those of spider dragline silk. Our findings suggest that the incorporation of rare earth ions (La3+ or Eu3+) into the silk fibers contributes to this enhancement. Structure analysis reveals a reduction in content and an improvement in orientation of ß-sheet nanocrystals in silk fibers. X-ray photoelectron spectroscopy analysis confirms the chemical interaction between rare earth ions with ß-sheet nanocrystals. The structural evolution and chemical interactions lead to the simultaneous enhancement in both strength and toughness. This work presents a simple, scalable, and effective strategy for producing ultra-strong and tough silk fibers with potential applications in areas requiring super structural materials, such as personal protection and aerospace.


Assuntos
Bombyx , Seda , Animais , Seda/química , Bombyx/metabolismo , Resistência à Tração , Íons/metabolismo , Dieta
13.
Acta Biochim Biophys Sin (Shanghai) ; 55(10): 1659-1667, 2023 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-37654074

RESUMO

Aging is a pressing global health issue that is linked to various diseases, such as diabetes and Alzheimer's disease. It is well known that glycation plays a pathological role in the aging process and age-related diseases. Thus, it is of great significance to discover protein glycation at an early stage for monitoring and intervention in the aging process. However, the endogenous age-related early-stage glycated proteome remains insufficiently profiled. To address this research gap, our study focuses on assessing glycated proteomics profiles in the serum of mice. We employ a robust and quantitative strategy previously developed by our team, to analyze endogenous glycated proteome in serum samples of 4 age groups of mice (10 weeks, 16 weeks, 48 weeks and 80 weeks). In total, 2959 endogenous glycated peptides corresponding to 296 serum proteins are identified from 48 runs of serum samples from 16 mice across the four age groups. By comparing these glycated peptides between adjacent age groups, we discover 49 glycated peptides from 35 proteins that show significant upregulation between the 48-week and 80-week age groups. Furthermore, we identify 10 glycated proteins (or protein groups) that are significantly upregulated only between the 48-week and 80-week age groups, including lecithin-cholesterol acyltransferase (LCAT) and apolipoprotein A-II (Apo A-II). These novel findings provide unique signatures for understanding the aging process and age-related diseases. By shedding light on the early-stage glycated proteome, our study contributes valuable insights that may have implications for future interventions and therapeutic approaches.


Assuntos
Diabetes Mellitus , Proteoma , Animais , Camundongos , Proteoma/metabolismo , Glicosilação , Proteínas Glicadas , Peptídeos/metabolismo
14.
Injury ; 54(10): 111014, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37677857

RESUMO

OBJECTIVES: Injury to the tibiofibular syndesmosis is a common complication of ankle fractures. Currently, it is challenging to determine the stability of the tibiofibular joint caused by ankle fractures during surgery. This study aims to establish a standardized method for dynamically evaluating the stability of the inferior tibiofibular joint under intraoperative ultrasound and assess its utility in surgery, thereby assisting in determining the necessity for fixation of the inferior tibiofibular joint after fracture reduction and fixation. METHODS: The stability of the inferior tibiofibular joint was assessed using an intraoperative ultrasonic external rotation stress test, with a torque set at 7.2 N·m. The measured parameters included the width of the inferior tibiofibular space in neutral (N) and external rotation (E) positions, stretch ratio (E/N), and injured/healthy side stretch ratio (I/H). Patients with Weber B or C type ankle fractures were selected as participants. RESULTS: For the case with Weber C fracture, the N measurement was 4.22 mm after fracture fixation, while E measured 5.77 mm and E/N ratio was 1.37, which were larger than those on the healthy side (N: 4.17, E: 4.50, E/N:1.08), with an I/H ratio of 1.27. Intraoperative X-ray revealed instability of the inferior tibiofibular joint. After inserting a tibiofibular screw, the N measurement was 4.20 mm, while the E measurement recorded 4.32 mm, resulting in an E/N ratio of 1.03 and an I/H ratio of 0.95, indicating improved joint stability. For the Weber B fracture case, the N measurement was 3.55 mm after fracture fixation, while E measured 3.98 mm and the E/N ratio was 1.12, slightly lower than those on the healthy side (N: 3.94, E: 4.47, E/N: 1.13), with an I/H ratio of 0.99. The intraoperative X-ray revealed stability of the inferior tibiofibular joint. Therefore, no further fixation was performed on it. CONCLUSION: Standardized intraoperative ultrasound stress test allows for real-time, dynamic assessment of the stability of the inferior tibiofibular joint after ankle fracture reduction and fixation, which can help guide the fixation of the inferior tibiofibular joint, thereby reducing the risk of postoperative traumatic arthritis.


Assuntos
Fraturas do Tornozelo , Articulação do Tornozelo , Humanos , Articulação do Tornozelo/diagnóstico por imagem , Articulação do Tornozelo/cirurgia , Fraturas do Tornozelo/diagnóstico por imagem , Fraturas do Tornozelo/cirurgia , Ultrassonografia , Extremidade Inferior , Parafusos Ósseos
15.
Nat Genet ; 55(10): 1651-1664, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37770635

RESUMO

Coronary artery calcification (CAC), a measure of subclinical atherosclerosis, predicts future symptomatic coronary artery disease (CAD). Identifying genetic risk factors for CAC may point to new therapeutic avenues for prevention. Currently, there are only four known risk loci for CAC identified from genome-wide association studies (GWAS) in the general population. Here we conducted the largest multi-ancestry GWAS meta-analysis of CAC to date, which comprised 26,909 individuals of European ancestry and 8,867 individuals of African ancestry. We identified 11 independent risk loci, of which eight were new for CAC and five had not been reported for CAD. These new CAC loci are related to bone mineralization, phosphate catabolism and hormone metabolic pathways. Several new loci harbor candidate causal genes supported by multiple lines of functional evidence and are regulators of smooth muscle cell-mediated calcification ex vivo and in vitro. Together, these findings help refine the genetic architecture of CAC and extend our understanding of the biological and potential druggable pathways underlying CAC.


Assuntos
Aterosclerose , Doença da Artéria Coronariana , Humanos , Aterosclerose/genética , População Negra/genética , Doença da Artéria Coronariana/genética , Estudo de Associação Genômica Ampla , Fatores de Risco , População Europeia/genética
16.
Analyst ; 148(20): 5002-5011, 2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37728433

RESUMO

Human angiotensin-converting enzyme 2 (hACE2) is the primary receptor for cellular entry of SARS-CoV-2 into human host cells. hACE2 is heavily glycosylated and glycans on the receptor may play a role in viral binding. Thus, comprehensive characterization of hACE2 glycosylation could aid our understanding of interactions between the receptor and SARS-CoV-2 spike (S) protein, as well as provide a basis for the development of therapeutic drugs targeting this crucial interaction. Herein, 138 N-glycan compositions were identified, most of which are complex-type N-glycans, from seven N-glycosites of hACE2. Among them, 67% contain at least one sialic acid residue. At the level of glycopeptides, the overall quantification of sialylated glycan isomers observed on the sites N322 and N546 have a higher degree of NeuAc (α2-3)Gal (over 80.3%) than that of other N-glycosites (35.6-71.0%). In terms of O-glycans, 69 glycan compositions from 12 O-glycosites were identified, and especially, the C-terminus of hACE2 is heavily O-glycosylated. The terminal sialic acid linkage type of H1N1S1 and H1N1S2 are covered highly with α2,3-sialic acid. These findings could aid the investigation of the interaction between SARS-CoV-2 and human host cells.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Enzima de Conversão de Angiotensina 2/metabolismo , Glicosilação , Ácido N-Acetilneuramínico , Polissacarídeos/química , Ligação Proteica , SARS-CoV-2/metabolismo
17.
Anal Chem ; 95(35): 13055-13063, 2023 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-37611173

RESUMO

S-acylation is a widespread lipidation form in eukaryotes in which various fatty acids can be covalently attached to specific cysteine residues. However, due to the low reactivity of the lipid moieties and lack of specific antibodies, purification of intact S-acylated peptides remains challenging. Here, we developed a pretreatment method for direct separation and global analysis of endogenously intact S-acylated peptides by nanographite fluoride-based solid-phase extraction (nGF-SPE), together with the investigation and optimization of the enrichment procedure as well as the LC-MS/MS analysis process. Consequently, we performed the first global profiling of endogenously intact S-acylated peptides, with 701 S-palmitoylated peptides from HeLa cell lysates in a restricted search. Furthermore, coupling the nGF-SPE method with open search mode, altogether 1119 intact S-acylated peptides were identified with the attached palmitate, palmitoleate, myristate, and octanoate chain, respectively, providing a global insight into the endogenously heterogeneous modification state. Notably, we found and validated that S-palmitoleoylation (C16:1) provided less affinity toward lipid rafts compared with S-palmitoylation (C16:0). This study developed the first straightforward way to characterize endogenously intact S-acylated peptides on a proteome-wide scale, providing the modified residues together with their attached lipid moieties simultaneously, which paves the way for further understanding of protein S-acylation.


Assuntos
Fluoretos , Espectrometria de Massas em Tandem , Animais , Humanos , Cromatografia Líquida , Células HeLa , Acilação , Diferenciação Celular , Mamíferos
18.
Mater Horiz ; 10(10): 4626-4634, 2023 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-37594192

RESUMO

While nanomaterials possess impressive mechanical properties at the microscale level, their macroscopic assemblies usually exhibit inferior properties due to ineffective stress transfer among individual nanomaterials. This issue is addressed in this work by achieving strong interfacial interactions between aramid nanofibers and graphene oxide nanosheets through a neutralization reaction in a dipolar solvent and regulating the topological properties using polymer micelles to form a compact structure, leading to the formation of a super-strong and super-tough nanofiber film. The film was prepared through a sol-gel-film transition process and possesses a nacre-like microstructure that deflects microcracks and prevents them from propagating straight through the film. Remarkably, it demonstrates a tensile strength of 599.0 MPa and a toughness of 37.7 MJ m-3, which are 491.0% and 1094.5% that of a pristine aramid nanofiber film, respectively. In addition, it exhibits excellent tolerance to extreme temperatures (-196 to 300 °C) and fatigue resistance to folding 10 000 times. Overall, this study presents a synergistic interfacial and topological enhancement strategy for constructing nanomaterial-based composites with inherited properties from the nanoscale building blocks to the macroscale structural material.

19.
Prev Med ; 175: 107674, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37604289

RESUMO

Numerous studies have revealed associations between high intake of whole grains and reduced risk of various cancers. Yet, in recent decades, the traditional Chinese diets have been challenged by reduction in whole grains and increase in refined grains. To assess the impact of this dietary transition on cancer prevention, we analyzed the time trend of whole grain intake using nationally representative sampling data of over 15 thousand individuals from the China Health and Nutrition Survey. We applied the comparative risk assessment method to estimate the population attributable fraction of cancers due to insufficient whole grain intake from 1997 to 2011 and projected the trend of whole grain intake and the associated burden of cancers to 2035. We found a significant decrease of approximately 59% of whole grain intake in the Chinese population from 1997 to 2011. Compared with 1997, insufficient intake of whole grains was responsible for 9940 more cases of breast cancer, 12,903 more cases of colorectal cancer and 434 more cases of pancreatic cancer in 2011. Our projections suggest that if every Chinese would consume 125 g whole grain per day as recommended by the latest Chinese Dietary Guidelines, 0.63% bladder cancer, 8.98% breast cancer, 15.85% colorectal cancer, 3.86% esophageal cancer, 2.52% liver cancer and 2.22% pancreatic cancer (totaling 186,659 incident cases) could theoretically be averted by 2035. Even if everyone maintained the 2011 whole grain intake level, an estimated 8.38% of cancer events could still be prevented by 2035.

20.
Artigo em Inglês | MEDLINE | ID: mdl-37540936

RESUMO

Echinococcosis caused by larval stage of the genus Echinococcus, is a serious and potentially fatal parasitic zoonosis distributed globally. The two types of the disease in human are cystic echinococcosis (CE) and alveolar echinococcosis (AE). As the biological and encysting characteristics of the parasite, early diagnosis remains to address. In the present study, we demonstrate the value of Immunoglobulin G (IgG) glycome as a potential diagnostic biomarker for echinococcosis. Serum IgG glycome profiles were analyzed by ultra-performance liquid chromatography in a cohort comprised of 127 echinococcosis patients, of them 98 were diagnosed as CE and 29 as AE. IgG N-glycome analysis in pretreatment serum of echinococcosis patients presents 25 glycans and 64 derived traits. Compared with IgG glycans of healthy control group, neutral glycans, fucosylation and agalactosylated N-glycans increased while sialylation and galactosylation decreased in echinococcosis patients. Combined with a machine-learning-based approach, we built three biomarker combinations to distinguish CE, AE and healthy controls. Meanwhile, galactosylation, sialylation and A2BG2S1 in IgG glycan profiles were evidently associated with different types of CE (from CE1 to CE5). Our findings suggest that the alterations in IgG N-glycome may be of value in CE and AE diagnosis and follow-up CE disease progress. The role of IgG N-glycans as diagnostic biomarker remains to be verified in future study.


Assuntos
Equinococose , Imunoglobulina G , Humanos , Glicômica , Equinococose/diagnóstico , Biomarcadores , Polissacarídeos
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