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1.
Cell ; 187(11): 2703-2716.e23, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38657602

RESUMO

Antigen presentation defects in tumors are prevalent mechanisms of adaptive immune evasion and resistance to cancer immunotherapy, whereas how tumors evade innate immunity is less clear. Using CRISPR screens, we discovered that IGSF8 expressed on tumors suppresses NK cell function by interacting with human KIR3DL2 and mouse Klra9 receptors on NK cells. IGSF8 is normally expressed in neuronal tissues and is not required for cell survival in vitro or in vivo. It is overexpressed and associated with low antigen presentation, low immune infiltration, and worse clinical outcomes in many tumors. An antibody that blocks IGSF8-NK receptor interaction enhances NK cell killing of malignant cells in vitro and upregulates antigen presentation, NK cell-mediated cytotoxicity, and T cell signaling in vivo. In syngeneic tumor models, anti-IGSF8 alone, or in combination with anti-PD1, inhibits tumor growth. Our results indicate that IGSF8 is an innate immune checkpoint that could be exploited as a therapeutic target.


Assuntos
Imunidade Inata , Imunoterapia , Células Matadoras Naturais , Neoplasias , Animais , Feminino , Humanos , Camundongos , Apresentação de Antígeno , Linhagem Celular Tumoral , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Proteínas de Membrana/metabolismo , Camundongos Endogâmicos C57BL , Neoplasias/imunologia , Neoplasias/terapia
2.
Insect Mol Biol ; 33(3): 246-258, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38323672

RESUMO

Molybdenum cofactor sulfurase (MoCoS) is a key gene involved in the uric acid metabolic pathway that activates xanthine dehydrogenase to synthesise uric acid. Uric acid is harmful to mammals but plays crucial roles in insects, one of which is the immune responses. However, the function of Bombyx mori MoCoS in response to BmNPV remains unclear. In this study, BmMoCoS was found to be relatively highly expressed in embryonic development, gonads and the Malpighian tubules. In addition, the expression levels of BmMoCoS were significantly upregulated in three silkworm strains with different levels of resistance after virus infection, suggesting a close link between them. Furthermore, RNAi and overexpression studies showed that BmMoCoS was involved in resistance to BmNPV infection, and its antivirus effects were found to be related to the regulation of uric acid metabolism, which was uncovered by inosine- and febuxostat-coupled RNAi and overexpression. Finally, the BmMoCoS-mediated uric acid pathway was preliminarily confirmed to be a potential target to protect silkworms from BmNPV infection. Overall, this study provides new evidence for elucidating the molecular mechanism of silkworms in response to BmNPV infection and new strategies for the prevention of viral infections in sericulture.


Assuntos
Bombyx , Proteínas de Insetos , Nucleopoliedrovírus , Animais , Bombyx/enzimologia , Bombyx/genética , Bombyx/virologia , Proteínas de Insetos/metabolismo , Proteínas de Insetos/genética , Larva/metabolismo , Larva/crescimento & desenvolvimento , Larva/virologia , Metaloproteínas/metabolismo , Metaloproteínas/genética , Cofatores de Molibdênio , Nucleopoliedrovírus/fisiologia , Interferência de RNA , Ácido Úrico/metabolismo
3.
J Immunol ; 208(10): 2425-2435, 2022 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-35437281

RESUMO

Tumor metastasis is the primary cause of mortality in patients with cancer. Several chemokines are identified as important mediators of tumor growth and/or metastasis. The level of CXCL13 has been reported to be elevated in serum or tumor tissues in patients, which mainly functions to attract B cells and follicular B helper T cells. However, the role of CXCL13 in cancer growth and metastasis is not fully explored. In the current study, we found that CXCL13 is not a strong mediator to directly promote tumor growth; however, the mice deficient in CXCL13 had far fewer pulmonary metastatic foci than did the wild-type mice in experimental pulmonary metastatic models. In addition, Cxcl13 -/- mice also had fewer IL-10-producing B cells (CD45+CD19+IL-10+) in the metastatic tumor immune microenvironment than those of wild-type C57BL/6 mice, resulting in an enhanced antitumor immunity. Notably, CXCL13 deficiency further improved the efficacy of a traditional chemotherapeutic drug (cyclophosphamide), as well as that of anti-programmed death receptor-1 immunotherapy. These results suggested that CXCL13 has an important role in regulating IL-10-producing B cells in tumor metastasis and might be a promising target for improving therapeutic efficiency and stimulating tumor immunity in future cancer therapy.


Assuntos
Linfócitos B Reguladores , Quimiocina CXCL13 , Neoplasias , Animais , Linfócitos B Reguladores/imunologia , Linfócitos B Reguladores/patologia , Quimiocina CXCL13/imunologia , Humanos , Interleucina-10 , Camundongos , Camundongos Endogâmicos C57BL , Metástase Neoplásica , Neoplasias/imunologia , Neoplasias/patologia , Microambiente Tumoral
4.
Clin Oral Investig ; 28(1): 121, 2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38280038

RESUMO

OBJECTIVE: We aimed to develop a tool for virtual orthodontic bracket removal based on deep learning algorithms for feature extraction from bonded teeth and to demonstrate its application in a bracket position assessment scenario. MATERIALS AND METHODS: Our segmentation network for virtual bracket removal was trained using dataset A, containing 978 bonded teeth, 20 original teeth, and 20 brackets generated by scanners. The accuracy and segmentation time of the network were tested by dataset B, which included an additional 118 bonded teeth without knowing the original tooth morphology. This tool was then applied for bracket position assessment. The clinical crown center, bracket center, and orientations of separated teeth and brackets were extracted for analyzing the linear distribution and angular deviation of bonded brackets. RESULTS: This tool performed virtual bracket removal in 2.9 ms per tooth with accuracies of 98.93% and 97.42% (P < 0.01) in datasets A and B, respectively. The tooth surface and bracket characteristics were extracted and used to evaluate the results of manually bonded brackets by 49 orthodontists. Personal preferences for bracket angulation and bracket distribution were displayed graphically and tabularly. CONCLUSIONS: The tool's efficiency and precision are satisfactory, and it can be operated without original tooth data. It can be used to display the bonding deviation in the bracket position assessment scenario. CLINICAL SIGNIFICANCE: With the aid of this tool, unnecessary bracket removal can be avoided when evaluating bracket positions and modifying treatment plans. It has the potential to produce retainers and orthodontic devices prior to tooth debonding.


Assuntos
Aprendizado Profundo , Colagem Dentária , Braquetes Ortodônticos , Colagem Dentária/métodos , Descolagem Dentária/métodos , Microscopia Eletrônica de Varredura
5.
Anal Chem ; 95(47): 17166-17169, 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-37966263

RESUMO

As a simple soft ionization method, photoionization (PI) is often coupled with mass spectrometry (MS) for the direct analysis of volatile organic compounds (VOCs). PI enables selective ionization of analytes, but the ion yield is generally not high due to the limited light intensity of the ultraviolet lamp. Here, a hydrogen-assisted photoionization (HAPI) strategy was developed and integrated into a miniature ion trap mass spectrometer. In particular, hydrogen was introduced as a versatile buffer gas to facilitate both photoionization and ion trap operation. This can increase the ion yields by up to 2 orders of magnitude compared to conventional PI-MS, with a low hydrogen consumption (less than 100 µL) for each analysis. The generation of protonated ions indicates a specific photochemical process in HAPI, which has also been studied and initially revealed. The detection of various VOCs and plant volatile gases confirmed the versatility and practicality of the HAPI technology.

6.
Anal Chem ; 95(4): 2348-2355, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36609163

RESUMO

To figure out the reason for the drawback of the stored waveform inverse Fourier transform (SWIFT) waveform and realize the high-resolution ion isolation on the miniaturized linear ion trap mass spectrometer, we studied the efficiency that ions can be excited under different excitation durations and amplitudes at different frequencies and compared the overlap ratios of the effective excitation frequency bandwidths of the adjacent ions. According to this, we proposed a new coarse-to-fine isolation waveform named SWIFTSIN. By superposing one or more sinusoidal waveforms on the SWIFT waveform and modulating the phases of the superposed sinusoidal waveforms, the generated SWIFTSIN waveform can achieve unit mass isolation on the miniaturized linear ion trap mass spectrometer without reducing the intensity of the target ion. The isolation ability of the SWIFTSIN waveform was verified by isolating a single isotope peak in the mixed samples.

7.
Anal Chem ; 95(47): 17407-17415, 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-37963290

RESUMO

The mass spectrometer is an important tool for modern chemical analysis and detection. Especially, the emergence of miniature mass spectrometers has provided new tools for field analysis and detection. The resolution of a mass spectrometer reflects the ability of the instrument to discriminate between adjacent mass-to-charge ratio ions, and the higher the resolution, the better the discrimination of complex mixtures. Quadrupole ion traps are generally considered as a low-resolution mass spectrometry method, but they have gained wide attention and development in recent years because of their suitability for miniaturization and high qualitative capability. For an ion trap mass spectrometer, the mass sensitivity and resolution can be mutually constrained and need to be balanced by setting an appropriate scanning speed. In this study, a super-resolution U-net algorithm (SR-Unet) is proposed for ion trap mass spectrometry, which can estimate the possible ions from the overlapping ion peaks of low-resolution spectra and improve the equivalent resolution while ensuring sufficient sensitivity and analysis speed of the instrument. By determining the mass spectra of a linear ion trap mass spectrometer (LTQ XL) in Turbo and Normal scan modes, the same unit mass resolution as that at a scan speed of 16,667 Da/s was successfully obtained at 125,000 Da/s. Also, the experiments demonstrated that the algorithm is capable of the mass-to-charge ratio and instrument migration. SR-Unet can be migrated and applied to a miniature mass spectrometer for cruise detection of volatile organic compounds (VOCs), and the identification of VOC species in Photochemical Assessment Monitoring Stations (PAMS) was improved from 31 to 50 species with the same monitoring and analysis speed requirement. Further, super-unit mass resolution peptide detection was achieved on a miniature mass spectrometer with the help of the SR-Unet algorithm, which reduced the full width at half-maxima (FWHM) of bradykinin divalent ions (m/z 531) from 0.35 to 0.15 Da at a scan speed of 375 Da/s and improved the equivalent resolution to 3540. The proposed method provides a new idea to enhance the field mixture detection capability of miniature ion trap mass spectrometers.

8.
Hepatology ; 76(1): 66-77, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35007334

RESUMO

BACKGROUND AND AIMS: The study objective was to compare the effectiveness of microwave ablation (MWA) and laparoscopic liver resection (LLR) on solitary 3-5-cm HCC over time. APPROACH AND RESULTS: From 2008 to 2019, 1289 patients from 12 hospitals were enrolled in this retrospective study. Diagnosis of all lesions were based on histopathology. Propensity score matching was used to balance all baseline variables between the two groups in 2008-2019 (n = 335 in each group) and 2014-2019 (n = 257 in each group) cohorts, respectively. For cohort 2008-2019, during a median follow-up of 35.8 months, there were no differences in overall survival (OS) between MWA and LLR (HR: 0.88, 95% CI 0.65-1.19, p = 0.420), and MWA was inferior to LLR regarding disease-free survival (DFS) (HR 1.36, 95% CI 1.05-1.75, p = 0.017). For cohort 2014-2019, there was comparable OS (HR 0.85, 95% CI 0.56-1.30, p = 0.460) and approached statistical significance for DFS (HR 1.33, 95% CI 0.98-1.82, p = 0.071) between MWA and LLR. Subgroup analyses showed comparable OS in 3.1-4.0-cm HCCs (HR 0.88, 95% CI 0.53-1.47, p = 0.630) and 4.1-5.0-cm HCCs (HR 0.77, 95% CI 0.37-1.60, p = 0.483) between two modalities. For both cohorts, MWA shared comparable major complications (both p > 0.05), shorter hospitalization, and lower cost to LLR (all p < 0.001). CONCLUSIONS: MWA might be a first-line alternative to LLR for solitary 3-5-cm HCC in selected patients with technical advances, especially for patients unsuitable for LLR.


Assuntos
Carcinoma Hepatocelular , Ablação por Cateter , Laparoscopia , Neoplasias Hepáticas , Carcinoma Hepatocelular/patologia , Hepatectomia , Humanos , Neoplasias Hepáticas/patologia , Micro-Ondas/uso terapêutico , Pontuação de Propensão , Estudos Retrospectivos , Resultado do Tratamento
9.
Exp Dermatol ; 32(11): 1900-1914, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37622736

RESUMO

Psoriasis is an autoimmune skin disease that often co-occurs with psychological morbidities such as anxiety and depression, and psychosocial issues also lead psoriasis patients to avoid other people. However, the precise mechanism underlying the comorbidity of psoriasis and anxiety is unknown. Also, whether the social avoidance phenomenon seen in human patients also exists in psoriasis-like animal models remains unknown. In the present study, anxiety-like behaviours and social avoidance-like behaviours were observed in an imiquimod-induced psoriasis-like C57-BL6 mouse model along with typical psoriasis-like dermatitis and itch-like behaviours. The 11.7T resting-state functional magnetic resonance imaging showed differences in brain regions between the model and control group, and voxel-based morphometry showed that the grey matter volume changed in the basal forebrain region, anterior commissure intrabulbar and striatum in the psoriasis-like mice. Seed-based resting state functional connectivity analysis revealed connectivity changes in the amygdala, periaqueductal gray, raphe nuclei and lateral septum. We conclude that the imiquimod-induced psoriasis-like C57-BL6 mouse model is well suited for mechanistic studies and for performing preclinical therapeutic trials for treating anxiety and pathological social avoidance in psoriasis patients.


Assuntos
Imageamento por Ressonância Magnética , Psoríase , Humanos , Camundongos , Animais , Imiquimode , Ansiedade/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Psoríase/diagnóstico por imagem , Psoríase/psicologia
10.
Anal Bioanal Chem ; 415(26): 6441-6448, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37644320

RESUMO

The operation and performance of electrospray ionization (ESI) is affected by the surrounding environment. In this study, a compact sub-atmospheric pressure ESI (SAP-ESI) source was designed and fabricated using the 3D printing method. This source has a simple structure and is easy to operate, as the sample solution and auxiliary gas are continuously sucked into the source through the pressure difference. The compact and enclosed ionization chamber can reduce the fluctuation of the surrounding gas flow to ensure a remarkably stable (< 3%) electrospray. Moreover, the source can offer variable SAP conditions for ESI analysis. The yield of analyte ions increases with decreasing pressure, while the production of background ions is suppressed under these conditions. In the analysis of protein samples, SAP-ESI can increase the yield and charge state of ions, which may be due to the reduction of proton transfer between charged proteins and surrounding gas. The SAP-ESI source was then used to continuously monitor the extract aqueous solution of tea leaves, and to detect the carbendazim residues on the apple surface by coupling with the liquid extraction surface analysis technique. Experimental results demonstrate that the developed SAP-ESI is a stable, practical, and versatile ionization technique.

11.
Acta Pharmacol Sin ; 44(11): 2230-2242, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37402998

RESUMO

Acute kidney injury (AKI) is associated with high morbidity and mortality. Our previous study has demonstrated that TMEM16A, a Ca2+-activated chloride channel, contributes to renal fibrosis progression in chronic kidney disease. However, whether TMEM16A is involved in AKI is still unknown. In this study, we established cisplatin AKI mice model and found that TMEM16A expression was upregulated in the injured kidney. In vivo knockdown of TMEM16A effectively prevented cisplatin-induced tubular cell apoptosis, inflammation and kidney function loss. Western blot and transmission electron microscopy (TEM) revealed that TMEM16A knockdown inhibited Drp1 translocation from the cytoplasm to mitochondria and prevented mitochondrial fission in tubular cells. Consistently, in cultured HK2 cells, knockdown or inhibition of TMEM16A by shRNA or its specific inhibitor suppressed cisplatin-induced mitochondrial fission and its associated energy dysfunction, ROS accumulation, and cell apoptosis via inhibiting Drp1 activation. Further investigation showed that genetic knockdown or pharmacological inhibition of TMEM16A inhibited cisplatin-induced Drp1 Ser-616 site phosphorylation through ERK1/2 signaling pathway, whereas overexpression of TMEM16A promoted this effect. Treatment with Drp1 or ERK1/2 inhibitor could efficiently prevent cisplatin-induced mitochondrial fission. Collectively, our data suggest that TMEM16A inhibition alleviated cisplatin-induced AKI by preventing tubular cell mitochondrial fission through the ERK1/2 / Drp1 pathway. Inhibition of TMEM16A may be a novel therapeutic strategy for AKI.


Assuntos
Injúria Renal Aguda , Cisplatino , Camundongos , Animais , Cisplatino/efeitos adversos , Dinâmica Mitocondrial , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/prevenção & controle , Injúria Renal Aguda/metabolismo , Células Cultivadas , Transdução de Sinais , Apoptose
12.
Lasers Med Sci ; 38(1): 153, 2023 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-37393550

RESUMO

To evaluate the clinical efficacy of carbon dioxide laser in the treatment of female stress urinary incontinence and analyze the influencing factors. A total of 46 patients with stress urinary incontinence treated in the Affiliated Hospital of Nantong University from March 2021 to August 2022 were included through strict inclusion criteria and exclusion criteria. All patients were treated with transvaginal carbon dioxide laser therapy, and Patient Global Impression of Change (PGI-C) was used to evaluate patients' subjective satisfaction after treatment. The efficacy was evaluated by patient's subjective assessment of leakage, IngelmanSundberg scale, 1-h urine pad test, and international consultation on incontinence questionnaire short form (ICI-Q-SF) before and after treatment, and the adverse reactions after treatment were recorded. The treatment effect was divided into "significant effect group" and "no significant effect group" by subjective satisfaction and post-treatment-related scale evaluation. After laser treatment, patients' subjective symptom improved, the volume of 1-h urine pad test was reduced, and the ICI-Q-SF score was decreased, and the differences were statistically significant (P < 0.05). There was no significant difference in IngelmanSundberg scale before and after treatment (P = 1.00). Multivariate logistic regression analysis showed that pad test volume was significantly correlated with treatment effect (P = 0.007). Transvaginal carbon dioxide laser is a safe and effective method for the treatment of mild to moderate stress urinary incontinence in females. The less severe the urinary leakage, the better the treatment effect.


Assuntos
Lasers de Gás , Incontinência Urinária por Estresse , Humanos , Feminino , Incontinência Urinária por Estresse/radioterapia , Incontinência Urinária por Estresse/cirurgia , Lasers de Gás/uso terapêutico , Vagina/cirurgia , Resultado do Tratamento , Satisfação do Paciente , Dióxido de Carbono
13.
Entropy (Basel) ; 25(10)2023 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-37895498

RESUMO

The Minimum Vertex Weighted Coloring (MinVWC) problem is an important generalization of the classic Minimum Vertex Coloring (MinVC) problem which is NP-hard. Given a simple undirected graph G=(V,E), the MinVC problem is to find a coloring s.t. any pair of adjacent vertices are assigned different colors and the number of colors used is minimized. The MinVWC problem associates each vertex with a positive weight and defines the weight of a color to be the weight of its heaviest vertices, then the goal is the find a coloring that minimizes the sum of weights over all colors. Among various approaches, reduction is an effective one. It tries to obtain a subgraph whose optimal solutions can conveniently be extended into optimal ones for the whole graph, without costly branching. In this paper, we propose a reduction algorithm based on maximal clique enumeration. More specifically our algorithm utilizes a certain proportion of maximal cliques and obtains lower bounds in order to perform reductions. It alternates between clique sampling and graph reductions and consists of three successive procedures: promising clique reductions, better bound reductions and post reductions. Experimental results show that our algorithm returns considerably smaller subgraphs for numerous large benchmark graphs, compared to the most recent method named RedLS. Also, we evaluate individual impacts and some practical properties of our algorithm. Furthermore, we have a theorem which indicates that the reduction effects of our algorithm are equivalent to that of a counterpart which enumerates all maximal cliques in the whole graph if the run time is sufficiently long.

14.
Foot Ankle Surg ; 29(3): 233-238, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36754689

RESUMO

BACKGROUND: Metal screws are the most widely used in treating syndesmotic injuries, but failure and the rigidity of the screws can threaten the success of the treatment and increase the cost of care. We have provided an alternative with an olive wire and external fixator(OWEF) used for syndesmotic fixation. METHODS: A retrospective longitudinal follow-up study was conducted. From February 2011 to January 2018, 58 of 72 patients with ankle fractures and associated syndesmotic disruption were treated with either screw or OWEF fixation. The costs, complications, and clinical outcomes using Olerud-Molander score and Visual Analog score in screw and OWEF fixation group were compared. RESULTS: We found the severity of the injury, BMI of the patients and the different fixation methods were determinants of the complications and clinical outcomes. But if no malreduction of the syndesmosis was present, no difference in clinical result was detected. CONCLUSION: The OWEF method appeared to be at least equally functional and effective to screw fixation while maintaining possible lower complication rate. LEVELS OF CLINICAL EVIDENCE: Level 3.


Assuntos
Fraturas do Tornozelo , Olea , Humanos , Fraturas do Tornozelo/diagnóstico por imagem , Fraturas do Tornozelo/cirurgia , Seguimentos , Estudos Retrospectivos , Articulação do Tornozelo/cirurgia , Fixação Interna de Fraturas/métodos , Resultado do Tratamento , Parafusos Ósseos , Fixadores Externos
15.
Angew Chem Int Ed Engl ; 62(15): e202219048, 2023 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-36807450

RESUMO

Transition-metal-based oxyhydroxides are efficient catalysts in biomass electrooxidation towards fossil-fuel-free production of valuable chemicals. However, identification of active sites remains elusive. Herein, using cobalt oxyhydroxide (CoOOH) as the archetype and the electrocatalyzed glucose oxidation reaction (GOR) as the model reaction, we track dynamic transformation of the electronic and atomic structure of the catalyst using a suite of operando and ex situ techniques. We reveal that two types of reducible Co3+ -oxo species are afforded for the GOR, including adsorbed hydroxyl on Co3+ ion (µ1 -OH-Co3+ ) and di-Co3+ -bridged lattice oxygen (µ2 -O-Co3+ ). Moreover, theoretical calculations unveil that µ1 -OH-Co3+ is responsible for oxygenation, while µ2 -O-Co3+ mainly contributes to dehydrogenation, both as key oxidative steps in glucose-to-formate transformation. This work provides a framework for mechanistic understanding of the complex near-surface chemistry of metal oxyhydroxides in biomass electrorefining.

16.
BMC Immunol ; 23(1): 39, 2022 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-35965334

RESUMO

OBJECTIVE: This study was designed to investigate the role of the nucleotide-binding-domain -and leucine-rich repeat -containing (NLR) family, pyrin-domain-containing 3 (NLRP3) inflammasome in the pathogenesis of polymyositis (PM). METHODS: Immunochemistry was performed to analyze the NLRP3, caspase-1 and interleukin-1 beta (IL-1ß) expression in the muscle tissue of PM patients. Rat model of PM and C2C12 cell were used to investigate the potential role of NLRP3 inflammasome in PM. RESULTS: The percentage of CD 68+ macrophages, and the expression levels of NLRP3, caspase-1 and IL-1ß in the muscle tissue were elevated in 27 PM patients. LPS/ATP treatment resulted in activation of NLRP3 inflammasome and secretion of IL-1ß as well as interferons (IFNs) and monocyte chemotactic protein-1 (MCP-1) in the Raw 264.7 macrophages. Meanwhile, LPS/ATP challenged activation of NLRP3 inflammasome induced overexpression of major histocompatibility complex class I (MHC-I), a key molecular of PM in the co-cultured C2C12 cells. The effect was decreased by treatment of NLRP3 inflammasome inhibitor MCC950 or siRNA of NLRP3 inflammasome. These findings suggested certain levels of IL-1ß rather than IFNs up-regulated MHC-I expression in C2C12 cells. IL-1ß blockade using neutralizing IL-1ß monoclonal antibody or siRNA of IL-1ß suppressed MHC-I overexpression. In vivo, NLRP3 inflammasome inhibition by MCC950 reduced the expression of NLRP3, IL-1ß and MHC-I in the muscle tissue of PM modal rats. Also, it attenuated the intensity of muscle inflammation as well as the CRP, CK, and LDH levels in the serum. CONCLUSION: NLRP3/caspase-1/IL-1ß axis may play an important role in the development of PM. Inhibition of NLRP3 activation may hold promise in the treatment of PM.


Assuntos
Inflamassomos , Polimiosite , Trifosfato de Adenosina , Animais , Caspase 1/genética , Caspase 1/metabolismo , Inflamassomos/metabolismo , Lipopolissacarídeos , Complexo Principal de Histocompatibilidade , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Polimiosite/genética , RNA Interferente Pequeno , Ratos , Regulação para Cima
17.
Anal Chem ; 94(20): 7417-7424, 2022 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-35533348

RESUMO

With the advantages of rapid analysis, high sensitivity, and multicomponent identification, mass spectrometry (MS) is recognized as an appealing choice for high-throughput screening (HTS) analysis. Aiming at the small size, simple operation, and adequate performance, the development of miniature mass spectrometers has made great progress over the last 2 decades. Besides the essential analytical performance, simple operation and HTS capability are two other crucial features desired in miniature MS instruments. In this paper, an induced self-aspiration vacuum electrospray ionization source (ISA-VESI) was developed and coupled to a miniature ion trap mass spectrometer. A special timing sequence was designed to synchronize all the operation steps in each measurement, including dual-pulse sample injection, multipulse gas injection, MS analysis, and the movement of the homemade HTS platform used as the sampler. Then, the automatic high-throughput analysis of multiple samples can be accomplished with close coordination among the sample delivery, the sample introduction and ionization, and the ion trap operation. The measurement time of each ISA-VESI-MS analysis was about 7 s, with a sample consumption of less than 100 nL.


Assuntos
Ensaios de Triagem em Larga Escala , Espectrometria de Massas por Ionização por Electrospray , Vácuo
18.
Analyst ; 147(21): 4903-4909, 2022 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-36172822

RESUMO

Gas-droplet reactions occur at the microdroplet interface and tend to be greatly accelerated, which has great potential value in chemical analysis. To exploit such value, we combined online derivatization with secondary electrospray ionization (SESI) to implement a special ionization technique, termed reactive SESI, for rapid analysis of gas samples. Specifically, a suitable reagent was added to the spray solvent of SESI to initiate rapid derivatization of gas analytes in the microdroplets. The product ions are subsequently detected using a mass spectrometer. Compared to offline derivatization in bulk solution, reactive SESI can provide a higher yield and a faster reaction rate, and it allows the detection of intermediate ions. It is found that the signal changes of the analyte, intermediate, and product ions are highly consistent, indicating that a two-phase derivatization process may occur at the droplet interface. For reactive SESI-MS analysis, the use of a sub-ambient pressure SESI source can significantly improve the detection efficiency, making this technique truly useful for analytical applications, including the quantification of formaldehyde at tens of ppb levels in air, as well as the detection of various trace VOCs in exhaled breath from mice.


Assuntos
Espectrometria de Massas por Ionização por Electrospray , Compostos Orgânicos Voláteis , Camundongos , Animais , Espectrometria de Massas por Ionização por Electrospray/métodos , Compostos Orgânicos Voláteis/análise , Íons , Solventes , Formaldeído
19.
BMC Med Imaging ; 22(1): 84, 2022 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-35538520

RESUMO

OBJECTIVE: To investigate whether radiomics based on ultrasound images can predict lymphovascular invasion (LVI) of rectal cancer (RC) before surgery. METHODS: A total of 203 patients with RC were enrolled retrospectively, and they were divided into a training set (143 patients) and a validation set (60 patients). We extracted the radiomic features from the largest gray ultrasound image of the RC lesion. The intraclass correlation coefficient (ICC) was applied to test the repeatability of the radiomic features. The least absolute shrinkage and selection operator (LASSO) was used to reduce the data dimension and select significant features. Logistic regression (LR) analysis was applied to establish the radiomics model. The receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to evaluate the comprehensive performance of the model. RESULTS: Among the 203 patients, 33 (16.7%) were LVI positive and 170 (83.7%) were LVI negative. A total of 5350 (90.1%) radiomic features with ICC values of ≥ 0.75 were reported, which were subsequently subjected to hypothesis testing and LASSO regression dimension reduction analysis. Finally, 15 selected features were used to construct the radiomics model. The area under the curve (AUC) of the training set was 0.849, and the AUC of the validation set was 0.781. The calibration curve indicated that the radiomics model had good calibration, and DCA demonstrated that the model had clinical benefits. CONCLUSION: The proposed endorectal ultrasound-based radiomics model has the potential to predict LVI preoperatively in RC.


Assuntos
Neoplasias Retais , Área Sob a Curva , Humanos , Curva ROC , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/cirurgia , Estudos Retrospectivos , Ultrassonografia
20.
J Craniofac Surg ; 33(6): e588-e592, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35288503

RESUMO

OBJECTIVES: To assess the skeletal maturation in male children with unilateral cleft lip and palate (UCLP) in comparison to that of noncleft peers using the cervical vertebral maturation (CVM) method. METHODS: A sample of 149 male UCLP patients aged from 8- to 16-year-old and 447 age-matched orthodontic individuals without clefts was retrospectively compiled. Cervical vertebral maturation was assessed based on the cephalometric radiographs. RESULTS: The proportion of children in CVMSI and CVMSII was higher in the UCLP group compared to that in the noncleft group, but there was no significant difference in the CVM stage of the cleft patients compared to their noncleft peers. In the 12- to 14-year-old group, children with UCLP showed significantly delayed skeletal maturity in comparison with their noncleft peers. No significant difference was found in the other 3 age groups. There was a statistically significant correlation between the skeletal age and chronological age in both the UCLP group and the noncleft group. There was no significant difference in the mean age at CVMII and CVMIII between the cleft patients and noncleft peers. CONCLUSIONS: Males with UCLP aged 12- to 14-year-old have a statistically significant increased risk of delayed skeletal maturity in comparison with their noncleft peers. The chronological age is not an accurate indicator to assess the degree of skeletal maturation.


Assuntos
Fenda Labial , Fissura Palatina , Adolescente , Cefalometria/métodos , Criança , Fenda Labial/diagnóstico por imagem , Fenda Labial/cirurgia , Fissura Palatina/diagnóstico por imagem , Fissura Palatina/cirurgia , Humanos , Masculino , Estudos Retrospectivos
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