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1.
FASEB J ; 38(9): e23624, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38747001

RESUMO

The Retinitis pigmentosa GTPase regulator interacting protein 1-like (RPGRIP1L) gene encodes an important protein that performs various physiological functions. Variants of RPGRIP1L are related to a number of diseases. However, it is currently unknown whether RPGRIP1L is correlated with breast invasive carcinoma (BRCA). In BRCA tissue specimens, the expression of RPGRIP1L was found to be elevated in comparison to its levels in normal breast tissue. A notable decline in survival rates was associated with patients exhibiting heightened RPGRIP1L gene expression. Consistent with these findings, our data also show the above results. Furthermore, elevated expression of RPGRIP1L corresponded with a spectrum of unfavorable clinicopathological features, including the presence of human epidermal growth factor receptor 2 (HER2) positive, estrogen receptor (ER) positive, over 60 years old, T2, N0, and N3. At the same time, our research indicated that 50 genes and 15 proteins were positively related to RPGRIP1L, and that these proteins and genes were mostly involved in T cell proliferation, immune response, cytokine activity, and metabolic regulation. In addition, in the present study, there was a significant correlation between RPGRIP1L expression and immune cell infiltration. Finally, we found that four Chemicals could downregulate the expression of RPGRIP1L. Altogether, our results strongly indicated that RPGRIP1L might serve as a new prognostic biomarker for BRCA.


Assuntos
Biomarcadores Tumorais , Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Prognóstico , Pessoa de Meia-Idade , Regulação Neoplásica da Expressão Gênica , Idoso , Adulto
2.
J Clin Immunol ; 44(7): 155, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38922539

RESUMO

PURPOSE: Moesin (MSN) deficiency is a recently reported combined immunodeficiency, and few cases have been reported to date. We describe a Chinese patient with a novel mutation causing MSN deficiency and a novel phenotype. METHODS: Clinical and immunological data were collected. Whole-exome sequencing was performed to identify gene mutations. MSN protein expression and T cell proliferation and activation were determined by flow cytometry. Cell migration was confirmed with a Transwell assay. Autoantibody levels were analyzed using antigen microarrays. RESULTS: The patient was a 10-year-old boy who presented with recurrent fever, oral ulcers and dermatomyositis-like symptoms, such as periorbital edema, facial swelling, elevated creatine kinase levels, and abnormal electromyography and muscle biopsy results. Epstein-Barr virus (EBV) DNA was detected in the serum, cells and tissues of this patient. He further developed nasal-type NK/T-cell lymphoma. A novel hemizygous mutation (c.68 A > G, p.N23S) in the MSN gene was found. The immunological phenotype of this patient included persistent decreases in T and B lymphocyte counts but normal immunoglobulin IgG levels. The patient had attenuated MSN protein expression and impaired T-cell proliferation and migration. The proportions of Tfh cells and CD21low B cells in the patient were higher than those in the controls. Moreover, 82 IgG and 102 IgM autoantibodies were more abundant in the patient than in the healthy controls. CONCLUSIONS: The novel mutation N23S is pathogenic and leads to a severe clinical phenotype. EBV infection, tumor, and dermatomyositis-like autoimmune symptoms may be associated with MSN deficiency, further expanding the understanding of the disease.


Assuntos
Dermatomiosite , Infecções por Vírus Epstein-Barr , Proteínas dos Microfilamentos , Mutação , Humanos , Masculino , Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/genética , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/imunologia , Dermatomiosite/genética , Dermatomiosite/diagnóstico , Dermatomiosite/imunologia , Criança , Proteínas dos Microfilamentos/genética , Mutação/genética , Herpesvirus Humano 4 , Sequenciamento do Exoma , Síndromes de Imunodeficiência/genética , Síndromes de Imunodeficiência/diagnóstico , Autoanticorpos/sangue , Autoanticorpos/imunologia , Fenótipo , Linfócitos T/imunologia
3.
Opt Express ; 32(11): 19814-19824, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38859107

RESUMO

The intriguing photonic spin Hall effect (PSHE) of reflected Laguerre-Gaussian (LG) beams can be exhibited on the systems with optical anti-parity-time (Anti-PT) symmetry. During the reflection, the left/right circularly polarized (LCP/RCP) components of reflected LG beams are considered. By controlling parameters of the Anti-PT systems, the PSHE of reflected LCP/RCP can be identical and symmetrical with respect to incident-reflected plane (IRP). Due to gain/non-Hermitian effects of designed Anti-PT systems, special PSHE near the strong gain points (SGP) and exceptional points (EPs) can be obtained simulatively. Through analyses in PSHE of reflected LCP on four similar Anti-PT systems, specific conclusions that can even be extended to more general cases. Moreover, simulations of PSHE by simultaneously varying the incident angles * and imaginary/real dielectric constants Im/Re[ε] of the Anti-PT systems, specal PSHE and other novel optical phenomena with real applications can be revealed. So Anti-PT systems not only provide novel ways to regulate the PSHE of reflected LG beams, but also offer possibilities for new optical characteristics of devices.

4.
Environ Res ; 252(Pt 1): 118810, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38552829

RESUMO

Nitrate/nitrite-dependent anaerobic methane oxidation (n-DAMO) process offers a promising solution for simultaneously achieving methane emissions reduction and efficient nitrogen removal in wastewater treatment. Although nitrogen removal at a practical rate has been achieved by n-DAMO biofilm process, the mechanisms of biofilm formation and nitrogen transformation remain to be elucidated. In this study, n-DAMO biofilms were successfully developed in the membrane aerated moving bed biofilm reactor (MAMBBR) and removed nitrate at a rate of 159 mg NO3--N L-1 d-1. The obvious increase in the content of extracellular polymeric substances (EPS) indicated that EPS production was important for biofilm development. n-DAMO microorganisms dominated the microbial community, and n-DAMO bacteria were the most abundant microorganisms. However, the expression of biosynthesis genes for proteins and polysaccharides encoded by n-DAMO archaea was significantly more active compared to other microorganisms, suggesting the central role of n-DAMO archaea in EPS production and biofilm formation. In addition to nitrate reduction, n-DAMO archaea were revealed to actively express dissimilatory nitrate reduction to ammonium and nitrogen fixation. The produced ammonium was putatively converted to dinitrogen gas through the joint function of n-DAMO archaea and n-DAMO bacteria. This study revealed the biofilm formation mechanism and nitrogen-transformation network in n-DAMO biofilm systems, shedding new light on promoting the application of n-DAMO process.


Assuntos
Biofilmes , Reatores Biológicos , Metano , Nitratos , Oxirredução , Biofilmes/crescimento & desenvolvimento , Metano/metabolismo , Anaerobiose , Nitratos/metabolismo , Reatores Biológicos/microbiologia , Nitrogênio/metabolismo , Archaea/metabolismo , Archaea/genética , Archaea/fisiologia , Bactérias/metabolismo , Bactérias/genética , Eliminação de Resíduos Líquidos/métodos
5.
World J Surg Oncol ; 22(1): 128, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38725005

RESUMO

BACKGROUND: N6-methyladenosine (m6A) modification plays an important role in lung cancer. However, methyltransferase-like 14 (METTL14), which serves as the main component of the m6A complex, has been less reported to be involved in the immune microenvironment of lung cancer. This study aimed to analyze the relationship between METTL14 and the immune checkpoint inhibitor programmed death receptor 1 (PD-1) in lung cancer. METHODS: CCK-8, colony formation, transwell, wound healing, and flow cytometry assays were performed to explore the role of METTL14 in lung cancer progression in vitro. Furthermore, syngeneic model mice were treated with sh-METTL14 andan anti-PD-1 antibody to observe the effect of METTL14 on immunotherapy. Flow cytometry and immunohistochemical (IHC) staining were used to detect CD8 expression. RIP and MeRIP were performed to assess the relationship between METTL14 and HSD17B6. LLC cells and activated mouse PBMCs were cocultured in vitro to mimic immune cell infiltration in the tumor microenvironment. ELISA was used to detect IFN-γ and TNF-α levels. RESULTS: The online database GEPIA showed that high METTL14 expression indicated a poor prognosis in patients with lung cancer. In vitro assays suggested that METTL14 knockdown suppressed lung cancer progression. In vivo assays revealed that METTL14 knockdown inhibited tumor growth and enhanced the response to PD-1 immunotherapy. Furthermore, METTL14 knockdown enhanced CD8+T-cell activation and infiltration. More importantly, METTL14 knockdown increased the stability of HSD17B6 mRNA by reducing its m6A methylation. In addition, HSD17B6 overexpression promoted the activation of CD8+ T cells. CONCLUSION: The disruption of METTL14 contributed to CD8+T-cell activation and the immunotherapy response to PD-1 via m6A modification of HSD17B6, thereby suppressing lung cancer progression.


Assuntos
Linfócitos T CD8-Positivos , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares , Metiltransferases , Receptor de Morte Celular Programada 1 , Microambiente Tumoral , Animais , Feminino , Camundongos , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Proliferação de Células , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia/métodos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Ativação Linfocitária , Metiltransferases/metabolismo , Metiltransferases/genética , Camundongos Endogâmicos C57BL , Prognóstico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/metabolismo , Células Tumorais Cultivadas , Microambiente Tumoral/imunologia
6.
Biomed Chromatogr ; 38(4): e5826, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38205667

RESUMO

Artemisia argyi H.Lév. & Vaniot essential oil (AAEO) has shown pharmacological effects such as anti-inflammation, antioxidant, and anti-tumor properties. However, the protective effect of AAEO on lipopolysaccharide (LPS)-induced liver injury and its potential protective mechanism are still unclear. In this study, we used ultra-performance liquid chromatography tandem mass spectrometry metabolomics techniques to investigate the changes in liver tissue metabolites in mice exposed to LPS with or without AAEO treatment for 14 days. The biochemical results showed that compared with the control group, AAEO significantly reduced the levels of liver functional enzymes, suggesting a significant improvement in liver injury. In addition, the 18 differential metabolites identified by metabolomics were mainly involved in the reprogramming of arachidonic acid metabolism, tryptophan metabolism, and purine metabolism. AAEO could significantly inhibit the expression of COX-2, IDO1, and NF-κB; enhance the body's anti-inflammatory ability; and alleviate liver injury. In summary, our study identified the protective mechanism of AAEO on LPS-induced liver injury at the level of small molecular metabolites, providing a potential liver protective agent for the treatment of LPS-induced liver injury.


Assuntos
Artemisia , Doença Hepática Crônica Induzida por Substâncias e Drogas , Óleos Voláteis , Camundongos , Animais , Artemisia/química , Óleos Voláteis/farmacologia , Lipopolissacarídeos/efeitos adversos , Espectrometria de Massas em Tandem , Espectrometria de Massa com Cromatografia Líquida , Metabolômica
7.
Sensors (Basel) ; 24(16)2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39205112

RESUMO

Seals, sea lions, and other aquatic animals rely on their whiskers to identify and track underwater targets, offering valuable inspiration for the development of low-power, portable, and environmentally friendly sensors. Here, we design a single seal-whisker-like cylinder and conduct experiments to measure the forces acting on it with nine different upstream targets. Using sample sets constructed from these force signals, a convolutional neural network (CNN) is trained and tested. The results demonstrate that combining the seal-whisker-style sensor with a CNN enables the identification of objects in the water in most cases, although there may be some confusion for certain targets. Increasing the length of the signal samples can enhance the results but may not eliminate these confusions. Our study reveals that high frequencies (greater than 5 Hz) are irrelevant in our model. Lift signals present more distinct and distinguishable features than drag signals, serving as the primary basis for the model to differentiate between various targets. Fourier analysis indicates that the model's efficacy in recognizing different targets relies heavily on the discrepancies in the spectral features of the lift signals.


Assuntos
Redes Neurais de Computação , Animais , Vibrissas/fisiologia , Focas Verdadeiras/fisiologia
8.
Sensors (Basel) ; 24(15)2024 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-39124075

RESUMO

A low-cost, handheld centrifugal microfluidic system for multiplexed visual detection based on recombinase polymerase amplification (RPA) was developed. A concise centrifugal microfluidic chip featuring four reaction units was developed to run multiplexed RPA amplification in parallel. Additionally, a significantly shrunk-size and cost-effective handheld companion device was developed, incorporating heating, optical, rotation, and sensing modules, to perform multiplexed amplification and visual detection. After one-time sample loading, the metered sample was equally distributed into four separate reactors with high-speed centrifugation. Non-contact heating was adopted for isothermal amplification. A tiny DC motor on top of the chip was used to drive steel beads inside reactors for active mixing. Another small DC motor, which was controlled by an elaborate locking strategy based on magnetic sensing, was adopted for centrifugation and positioning. Visual fluorescence detection was optimized from different sides, including material, surface properties, excitation light, and optical filters. With fluorescence intensity-based visual detection, the detection results could be directly observed through the eyes or with a smartphone. As a proof of concept, the handheld device could detect multiple targets, e.g., different genes of African swine fever virus (ASFV) with the comparable LOD (limit of detection) of 75 copies/test compared to the tube-based RPA.


Assuntos
Técnicas de Amplificação de Ácido Nucleico , Técnicas de Amplificação de Ácido Nucleico/instrumentação , Técnicas de Amplificação de Ácido Nucleico/métodos , Vírus da Febre Suína Africana/isolamento & purificação , Vírus da Febre Suína Africana/genética , Dispositivos Lab-On-A-Chip , Limite de Detecção , Centrifugação/instrumentação , Animais , Smartphone , Técnicas Biossensoriais/instrumentação , Técnicas Biossensoriais/métodos , Técnicas Analíticas Microfluídicas/instrumentação , Técnicas Analíticas Microfluídicas/métodos , Técnicas Analíticas Microfluídicas/economia
9.
J Clin Immunol ; 43(4): 756-768, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36662455

RESUMO

PURPOSE: Summarize the characteristics of a large cohort of BCG disease and compare differences in clinical characteristics and outcomes among different genotypes and between primary immunodeficiency disease (PID) and patients without identified genetic etiology. METHODS: We collected information on patients with BCG disease in our center from January 2015 to December 2020 and divided them into four groups: chronic granulomatous disease (CGD), Mendelian susceptibility to mycobacterial disease (MSMD), severe combined immunodeficiency disease (SCID), and gene negative group. RESULTS: A total of 134 patients were reviewed, and most of them had PID. A total of 111 (82.8%) patients had 18 different types of pathogenic gene mutations, most of whom (91.0%) were classified with CGD, MSMD, and SCID. CYBB was the most common gene mutation (52/111). BCG disease behaves differently in individuals with different PIDs. Significant differences in sex (P < 0.001), age at diagnosis (P = 0.013), frequency of recurrent fever (P = 0.007), and vaccination-homolateral axillary lymph node enlargement (P = 0.039) and infection severity (P = 0.006) were noted among the four groups. The CGD group had the highest rate of males and the oldest age at diagnosis. The MSMD group had the highest probability of disseminated infection (48.3%). The course of anti-tuberculosis treatment and the survival time between patients with PID and without identified genetic etiology were similar. CONCLUSION: Greater than 80% of BCG patients have PID; accordingly, gene sequencing should be performed in patients with BCG disease for early diagnosis. BCG disease behaves differently in patients with different types of PID. Patients without identified genetic etiology had similar outcomes to PID patients, which hints that they may have pathogenic gene mutations that need to be discovered.


Assuntos
Doença Granulomatosa Crônica , Infecções por Mycobacterium , Imunodeficiência Combinada Severa , Criança , Humanos , Masculino , População do Leste Asiático , Doença Granulomatosa Crônica/diagnóstico , Doença Granulomatosa Crônica/epidemiologia , Doença Granulomatosa Crônica/genética , Infecções por Mycobacterium/diagnóstico , Infecções por Mycobacterium/epidemiologia , Infecções por Mycobacterium/genética , Estudos Retrospectivos , Imunodeficiência Combinada Severa/diagnóstico , Imunodeficiência Combinada Severa/epidemiologia , Imunodeficiência Combinada Severa/genética , Feminino
10.
Anal Chem ; 95(26): 9761-9768, 2023 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-37341462

RESUMO

Different from N-linked glycosylation, the core structures of mucin type O-glycans are much more diverse, and the sensitive interpretation of O-glycopeptide spectra remains a challenge. The Y-ion pattern, a series of Y-ions with known mass gaps derived from the penta-saccharide core structure of N-linked glycosylation, is exploited to facilitate N-glycopeptide identification from their spectra. However, the pattern of Y ions in O-glycopeptides has not been well studied. In this study, we found that the Y-ion patterns were also frequently observed in the spectra of O-glycopeptides, and a special search approach is presented to identify O-glycopeptides by utilizing the Y-ion patterns. In this strategy, theoretical O-glycan Y-ion patterns are constructed to match the experimental Y-ions in O-glycopeptide spectra, which enables the determination of the mass of some glycans and results in the reduction of searching space. In addition, a Y-ion pattern-based deisotope process is also developed to correct the precursor m/z. The new search strategy was applied to search a human serum data set, and 15.4%-199.0% more O-glycopeptide-spectrum matches (OGPSMs) and 19.6%-107.1% more glycopeptide sequence identifications than other state-of-the-art software tools were observed. This search mode, the O-Search-Pattern, has been implemented into our database search software, MS-Decipher, and is recommended for searching the O-glycopeptide spectra acquired by sceHCD (stepped collision energy higher-energy collisional dissociation).


Assuntos
Glicopeptídeos , Software , Humanos , Sequência de Aminoácidos , Glicopeptídeos/análise , Polissacarídeos/química , Íons
11.
Anal Chem ; 95(19): 7448-7457, 2023 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-37146305

RESUMO

Both N-linked glycosylation and O-linked glycosylation play essential roles in the onset and progression of various diseases including cancer, and N-/O-linked site-specific glycans have been proven to be promising biomarkers for the discrimination of cancer. However, the micro-heterogeneity and low abundance nature of N-/O-linked glycosylation, as well as the time-consuming and tedious procedures for the enrichment of O-linked intact glycopeptides, pose great challenges for their efficient and accurate characterization. In this study, we developed an integrated platform for the simultaneous enrichment and characterization of N- and O-linked intact glycopeptides from the same serum sample. By fine-tuning the experimental conditions, we demonstrated that this platform allowed the selective separation of N- and O-linked intact glycopeptides into two fractions, with 85.1% O-linked intact glycopeptides presented in the first fraction and 93.4% N-linked intact glycopeptides presented in the second fraction. Determined with high reproducibility, this platform was further applied to the differential analysis of serum samples of gastric cancer and health control, which revealed 17 and 181 significantly changed O-linked and N-linked intact glycopeptides. Interestingly, five glycoproteins containing both significant regulation of N- and O-glycosylation were observed, hinting potential co-regulation of different types of glycosylation during tumor progress. In summary, this integrated platform opened a potentially useful avenue for the global analysis of protein glycosylation and can serve as a useful tool for the characterization of N-/O-linked intact glycopeptides at the proteomics scale.


Assuntos
Glicopeptídeos , Glicoproteínas , Glicopeptídeos/análise , Reprodutibilidade dos Testes , Glicoproteínas/química , Glicosilação , Proteômica/métodos
12.
Anal Chem ; 95(26): 10017-10024, 2023 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-37345258

RESUMO

Mucin-type O-glycosylation (or O-GalNAcylation) takes place on most membrane and secretory proteins and is vital in regulating protein functions and many biological processes. O-GalNAcylation generally exhibits highly diverse and dense O-glycans linked to carrier proteins, which challenges the analysis of O-GalNAc glycoproteome using conventional methodologies. Here, we report an O-glycopeptide truncation strategy for the characterization of protein O-GalNAcylation in biological samples. The O-glycopeptide truncation strategy utilizes proteases or O-glycopeptidases for targeted cleavage of the enriched tryptic O-glycopeptides. It simplifies the O-glycopeptide backbones, O-glycans, or both, and has been shown to aid the improvement of the analytical coverage of O-GalNAc glycopeptides and glycoproteins. Tryptic O-glycopeptides covered with O-glycan clusters and terminal sialic acids could be well isolated by the hydrophilic-based enrichment approaches. The enriched O-glycopeptides are then enzymatically truncated into shorter or less multiply O-glycosylated peptides, which are more favorable for mass spectrometry detection and database search in general bottom-up glycoproteomics. We also investigate different proteolysis which could be well integrated into the O-glycopeptide truncation strategy. For large-scale analysis, we exploit different truncation schemes and identify nearly 2000 O-glycopeptides corresponding to 391 glycoproteins from 75 µL human serum, achieving the deepest-scale coverage of O-glycoproteins compared to other plasma/serum O-glycoproteomic studies. Together, the O-glycopeptide truncation strategy has great potential to facilitate the in-depth study of O-GalNAc glycoproteomics in biological samples.


Assuntos
Glicopeptídeos , Proteômica , Humanos , Glicopeptídeos/análise , Proteômica/métodos , Glicoproteínas/química , Glicosilação , Polissacarídeos/análise
13.
Chembiochem ; 24(24): e202300587, 2023 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-37783667

RESUMO

Most natural formate dehydrogenases (FDHs) exhibit NAD+ specificity, making it imperative to explore the engineering of FDH cofactor specificity for NADPH regeneration systems. The endogenous FDH of Komagataella phaffii (K. phaffii), termed KphFDH, is a typical NAD+ -specific FDH. However, investigations into engineering the cofactor specificity of KphFDH have yet to be conducted. To develop an NADP+ -specific variant of KphFDH, we selected D195, Y196, and Q197 as mutation sites and generated twenty site-directed variants. Through kinetic characterization, KphFDH/V19 (D195Q/Y196R/Q197H) was identified as the variant with the highest specificity towards NADP+ , with a ratio of catalytic efficiency (kcat /KM )NADP+ /(kcat /KM )NAD+ of 129.226. Studies of enzymatic properties revealed that the optimal temperature and pH for the reduction reaction of NADP+ catalyzed by KphFDH/V19 were 45 °C and 7.5, respectively. The molecular dynamics (MD) simulation was performed to elucidate the mechanism of high catalytic activity of KphFDH/V19 towards NADP+ . Finally, KphFDH/V19 was applied to an in vitro NADPH regeneration system with Meso-diaminopimelate dehydrogenase from Symbiobacterium thermophilum (StDAPDH/H227V). This study successfully created a KphFDH variant with high NADP+ specificity and demonstrated its practical applicability in an in vitro NADPH regeneration system.


Assuntos
NAD , Saccharomycetales , NADP/metabolismo , NAD/metabolismo , Formiato Desidrogenases/química , Saccharomycetales/metabolismo , Cinética
14.
Bioinformatics ; 38(7): 1911-1919, 2022 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-35020790

RESUMO

MOTIVATION: The interpretation of mass spectrometry (MS) data is a crucial step in proteomics analysis, and the identification of post-translational modifications (PTMs) is vital for the understanding of the regulation mechanism of the living system. Among various PTMs, glycosylation is one of the most diverse ones. Though many search engines have been developed to decipher proteomic data, some of them are difficult to operate and have poor performance on glycoproteomic datasets compared to advanced glycoproteomic software. RESULTS: To simplify the analysis of proteomic datasets, especially O-glycoproteomic datasets, here, we present a user-friendly proteomic database search platform, MS-Decipher, for the identification of peptides from MS data. Two scoring schemes can be chosen for peptide-spectra matching. It was found that MS-Decipher had the same sensitivity and confidence in peptide identification compared to traditional database searching software. In addition, a special search mode, O-Search, is integrated into MS-Decipher to identify O-glycopeptides for O-glycoproteomic analysis. Compared with Mascot, MetaMorpheus and MSFragger, MS-Decipher can obtain about 139.9%, 48.8% and 6.9% more O-glycopeptide-spectrum matches. A useful tool is provided in MS-Decipher for the visualization of O-glycopeptide-spectra matches. MS-Decipher has a user-friendly graphical user interface, making it easier to operate. Several file formats are available in the searching and validation steps. MS-Decipher is implemented with Java, and can be used cross-platform. AVAILABILITY AND IMPLEMENTATION: MS-Decipher is freely available at https://github.com/DICP-1809/MS-Decipher for academic use. For detailed implementation steps, please see the user guide. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Glicopeptídeos , Proteoma , Glicopeptídeos/análise , Glicopeptídeos/química , Proteômica/métodos , Software , Espectrometria de Massas , Peptídeos/química
15.
J Org Chem ; 88(15): 11278-11283, 2023 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-37486801

RESUMO

The partial oxidation of methane with O2 is significant due to its potential of providing abundant chemical feedstock. Only a few examples realized this type of reaction in homogeneous solvent systems, most of which are in low efficiency. Herein, we present a pyridine N-oxide-promoted cobalt-catalyzed O2-mediated methane oxidation to produce methylene bis(trifluoroacetate) with productivity over 500 molester molmetal-1 h-1.

16.
J Sep Sci ; 46(4): e2200767, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36538732

RESUMO

Radix Cudramiae, known as "Chuan-Po-Shi" in China, is a herbal medicine widely used in the southwest of the country, especially applied by the Miao and Zhuang nationalities for the treatment of liver diseases, such as acute liver injury and liver fibrosis. As a kind of ethnomedicine, the report on its chemical analysis was still blank, which restricted its clinical application. Therefore, this paper aimed to illustrate the chemical characteristics of Radix Cudramiae. A rapid analytical strategy based on ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry was developed to profile the natural small-molecular compounds in Radix Cudramiae, as well as the related prototypes and their metabolites in rats after drug administration. As a result, a total of 74 compounds were detected in the aqueous exact of Radix Cudramiae. In vivo, 45 chemicals including 16 prototypes and 29 metabolites in rat serum, along with 35 chemicals including 17 prototypes and 18 metabolites in rat liver, were screened out and identified. For the first time, the chemical constituents of Radix Cudramiae and their metabolic characteristics were discovered. It was hoped that this work would be beneficial for the safe and effective application of Radix Cudramiae in a clinic.


Assuntos
Medicamentos de Ervas Chinesas , Espectrometria de Massas em Tandem , Ratos , Animais , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/métodos , Ratos Sprague-Dawley , Medicamentos de Ervas Chinesas/análise , Cromatografia Gasosa-Espectrometria de Massas
17.
Altern Ther Health Med ; 29(7): 394-399, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37535911

RESUMO

Objective: To evaluate the clinical value of serum miR-124 and miR-200C combined with ultrasound NT in screening Down syndrome (DS) in elderly puerperae during the second trimester. Methods: 84 elderly pregnant women at high risk of DS were included (DS group: 58, non-DS group: 26). Serum markers (uE3, ß-hCG, AFP, miR-124, and miR-200C) were measured. Differences in markers between groups were analyzed, and a prediction model was used for DS evaluation. Results: The DS group showed higher smoking, drinking, and radiation exposure rates (P < .05). MOM values of ß-hCG and AFP were higher, while MOM value of uE3 was lower in the DS group (P < .05). MiR-124 and miR-200C were up-regulated in the DS group (P < .05). The prediction model and ROC curve analysis indicated the diagnostic value of the markers for DS (AUC = 0.779, 0.817, 0.780, 0.884, 0.887, P < .05). MiR-124 had the highest diagnostic specificity. Conclusion: MiR-124 and miR-200C can serve as auxiliary serum markers for early screening of DS in elderly puerperae during the second trimester.


Assuntos
Síndrome de Down , MicroRNAs , Gravidez , Humanos , Feminino , Idoso , Segundo Trimestre da Gravidez , Síndrome de Down/diagnóstico , Gonadotropina Coriônica Humana Subunidade beta , alfa-Fetoproteínas/análise , Biomarcadores
18.
Int J Mol Sci ; 24(1)2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36614179

RESUMO

Oral squamous cell carcinoma (OSCC) has a five-year survival rate of less than 50% due to its susceptibility to invasion and metastasis. Crosstalk between tumor cells and macrophages has been proven to play a critical role in tumor cell migration and invasion. However, the specific mechanisms by which tumor cells interact with macrophages have not been fully elucidated. This study sought to investigate the regulatory mechanism of tumor cell-derived alpha-enolase (ENO1) in the interaction between tumor cells and macrophages during OSCC progression. Small interfering RNA (siRNA) transfection and recombinant human ENO1 (rhENO1) stimulation were used to interfere with the interaction between tumor cells and macrophages. Our results showed that ENO1 was expressed higher in CAL27 cells than in HaCaT cells and regulated lactic acid release in CAL27 cells. Conditioned medium of macrophages (Macro-CM) significantly up-regulated the ENO1 mRNA expression and protein secretion in CAL27 cells. ENO1 promoted the migration and invasion of tumor cells by facilitating the epithelial-mesenchymal transition (EMT) through macrophages. ENO1 orchestrated the IL-6 secretion of macrophages via tumor cell-derived lactic acid and the paracrine ENO1/Toll-like receptor (TLR4) signaling pathway. In turn, IL-6 promoted the migration and invasion of tumor cells. Collectively, ENO1 promotes tumor cell migration and invasion by orchestrating IL-6 secretion of macrophages via a dual mechanism, thus forming a positive feedback loop to promote OSCC progression. ENO1 might be a promising therapeutic target which is expected to control OSCC progression.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Neoplasias Bucais/patologia , Interleucina-6/genética , Interleucina-6/metabolismo , Retroalimentação , Linhagem Celular Tumoral , Macrófagos/metabolismo , RNA Interferente Pequeno/metabolismo , Fosfopiruvato Hidratase/genética , Fosfopiruvato Hidratase/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Movimento Celular/fisiologia , Proliferação de Células , Transição Epitelial-Mesenquimal/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo
19.
Analyst ; 147(12): 2678-2686, 2022 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-35611759

RESUMO

Using an In2O3/WO3 type-II heterojunction modified fluorine-doped tin oxide (FTO) electrode as the photoanode and CdS quantum dots (QDs)-polydopamine nanospheres (PDA NSs) as the secondary antibody (Ab2) label, the photoelectrochemistry (PEC) sandwich immunosensing of the lung cancer marker CYFRA21-1 was studied. WO3 nanoplates were prepared by a hydrothermal method, In2O3 nanoporous spheres were prepared by a hydrothermal method followed by calcination, and the In2O3/WO3 type-II heterojunction with high PEC activity was prepared by ultrasonic mixing and cast-coating. PDA NSs with a high surface area can be loaded with abundant Ab2 molecules and many CdS QDs with an energy level well matched with the heterojunction, so the photocurrent signal can be amplified by the formation of a sandwich immunostructure. Through the simulation experiments of photoelectrode-modified chitosan films of varying thickness, the effective transport distance of photogenerated charges is preliminarily discussed. Under the optimized conditions, the photocurrent was linear with the common logarithm of CYFRA21-1 concentration from 100 fg mL-1 to 50 ng mL-1, with a limit of detection of 56 fg mL-1 (S/N = 3). The immunoassay of CYFRA21-1 in human serum samples gave satisfactory recovery results.


Assuntos
Técnicas Biossensoriais , Compostos de Cádmio , Índio , Nanosferas , Pontos Quânticos , Humanos , Antígenos de Neoplasias , Técnicas Biossensoriais/métodos , Compostos de Cádmio/química , Técnicas Eletroquímicas/métodos , Imunoensaio/métodos , Indóis , Queratina-19 , Limite de Detecção , Nanosferas/química , Polímeros , Pontos Quânticos/química , Sulfetos/química
20.
J Fluoresc ; 32(5): 1651-1660, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35612764

RESUMO

Chlamydia trachomatis (C. trachomatis) is a kind of intracellular parasitic microorganism, which can causes many diseases such as trachoma. In this strategy, a specific hairpin DNA with the probe loop as specific regions to recognize C. trachomatis DNA with strong affinity was designed, and its stem consisted of 24 AT base pairs as an effective template for hairpin DNA-CuNCs formation. In the absence of C. trachomatis DNA, the detection system showed strong orange fluorescence emission peaks at 606 nm. In the presence of C. trachomatis DNA, the conformation of DNA probe changed after hybridizing with C. trachomatis DNA. Then, the amount of hairpin DNA-CuNCs was reduced and resulted in low fluorescence emission. C. trachomatis DNA displayed a significant inhibitory effect on the synthesis of fluorescent hairpin DNA-CuNCs due to the competition between C. trachomatis DNA and the specific hairpin DNA. Under the optimal experimental conditions, different concentrations of C. trachomatis were tested and the results showed a good linear relationship in the range of 50 nM to 950 nM. Moreover, the detection limit was 18.5 nM and this detection method possessed good selectivity. Finally, the fluorescent biosensor had been successfully applied to the detection of C. trachomatis target sequence in HeLa cell lysate, providing a new strategy for the detection of C. trachomatis.


Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , Chlamydia trachomatis/genética , Cobre , DNA , Corantes Fluorescentes , Células HeLa , Humanos , Limite de Detecção , Espectrometria de Fluorescência/métodos
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